PMID- 11003762
TI - Evaluation of hemostatic and coagulation factor abnormalities in patients
undergoing the Fontan operation.
AB - OBJECTIVE: Low-velocity and nonlaminar flow patterns in the Fontan circulation,
as well as abnormal liver function in some patients, may partly account for the
coagulation abnormalities seen. We examined (1) coagulation factor abnormalities
before and after the Fontan procedure and (2) regional coagulation factor
abnormalities in the Fontan circulation. METHODS: Levels of factors V, VII, VIII,
X, antithrombin III, prothrombin fragment F1+2, protein C, and protein S were
measured in 2 groups of patients: In 14 patients undergoing the Fontan procedure,
blood was analyzed before the operation and 5 days after the operation (group 1).
The median age in this group was 3.2 years. In 10 patients who had undergone the
Fontan procedure, cardiac catheterization was performed and samples were taken
from the femoral vein, inferior vena cava, right atrium, and pulmonary artery
(group 2). The median age in this group was 6.2 years and the median follow-up
from the Fontan procedure was 4.1 years. RESULTS: In group 1 a significant
increase was noted postoperatively in the concentration of factor VIII (P<.001),
factor X (P<.001), and prothrombin fraction F1+2 (P <.001). A significant
decrease in the levels of antithrombin III (P <.001), protein C (P<.004), and
protein S (P<.02) was also found. The increase in factors VIII and X persisted at
4 years' follow-up in group 2 patients. In group 2, no significant regional
differences were observed between the coagulation factors measured at different
sites. CONCLUSIONS: There is an increased tendency toward coagulation after the
Fontan procedure. A prothrombotic state is supported by thrombin generation
associated with reduced antithrombin III concentration. This increase in
coagulation may contribute to the early and late risks of thromboembolism
observed after the Fontan procedure. We did not find any regional differences in
coagulation abnormalities in patients late after the Fontan procedure. Therefore,
the mechanisms and causes of the coagulation abnormalities remain unclear.
PMID- 11003763
TI - Preoperative autologous donation of blood for a simple cardiac anomaly: analysis
of children weighing under twenty kilograms.
AB - OBJECTIVE: Preoperative autologous donation of blood has been expanded to cardiac
operations in children. However, because of problems such as lack of cooperation
and hemodilution during cardiopulmonary bypass, its efficacy in small children is
unclear. This study clarifies the clinical significance of preoperative
autologous donation of blood in small children. METHODS: Thirty-seven patients
weighing under 20 kg (age range, 3-9 years; weight range, 13-20 kg) underwent
preoperative autologous donation and cardiac operations to treat a simple
anomaly. Twenty-five age- and weight-matched patients who were not cooperative or
refused preoperative autologous donation served as control subjects. Autologous
blood was collected by the simple or leapfrog method and stored as blood
components. Each collecting volume was 5 to 10 mL/kg. RESULTS: The donation was
performed 6+/-2 times during 50+/-16 days, and the whole storage volume was 48+/
17 mL/kg. There was no serious complication. The minimum hematocrit level
negatively correlated with the priming volume of cardiopulmonary bypass
(preoperative donation patients: P<.01, r(2) = 0.4; control subjects: P =.5, r
(2) = 0.03). Blood loss did not significantly differ between preoperative
donation patients and control subjects, and the transfused blood volumes were
43+/-13 mL/kg and 29+/-22 mL/kg, respectively. All of the autologous blood
products but fresh frozen plasma were reinfused. Use of homologous blood was
significantly less in preoperative donation patients than in control subjects (0%
vs 80%, P <.01). In preoperative donation patients postoperative recovery in
hemoglobin level was significantly better, which is concurrent with a higher
reticulocyte level. CONCLUSION: Preoperative autologous donation can be performed
safely with clinical efficacy, even in children under 20 kg. This can be improved
further through coupling with another procedure.
PMID- 11003764
TI - Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial
arrhythmias after thoracic surgery.
AB - OBJECTIVES: We sought to determine whether early prophylaxis with an L -type
calcium channel blocker reduces the incidence and morbidity associated with
atrial fibrillation/flutter and supraventricular tachyarrhythmia after major
thoracic operations. METHODS: In this randomized, double-blind, placebo
controlled study, 330 patients were given either intravenous diltiazem (n = 167)
or placebo (n = 163) immediately after lobectomy (> or =60 years) or
pneumonectomy (> or =18 years) and orally thereafter for 14 days. The primary end
point with respect to efficacy was a sustained (> or =15 minutes) or clinically
significant atrial arrhythmia during treatment. RESULTS: Postoperative atrial
arrhythmias (atrial fibrillation/flutter = 60; supraventricular tachyarrhythmias
= 5) occurred in 25 (15%) of the 167 patients in the diltiazem group and 40 (25%)
of the 163 patients in the placebo group (P = .03). When compared with placebo,
diltiazem nearly halved the incidence of clinically significant arrhythmias
(17/167 [10%] vs. 31/163 [19%], P = .02). The 2 groups did not differ in the
incidence of other major postoperative complications or overall duration or costs
of hospitalization. No serious adverse effects caused by diltiazem were seen.
CONCLUSIONS: After major thoracic operations, prophylactic diltiazem reduced the
incidence of clinically significant atrial arrhythmias in patients considered at
high risk for this complication.
PMID- 11003765
TI - Results of surgical treatment of lung cancer involving the diaphragm.
AB - OBJECTIVES: Lung cancers with diaphragmatic invasion are categorized as T3
lesions, but the surgical results have not been well known. We retrospectively
surveyed patients with resected primary lung cancers involving the diaphragm.
METHODS: A total of 16,771 patients underwent surgical resection for lung
carcinoma between 1986 and 1995 at 31 institutions of the Lung Cancer Surgical
Study Group in Japan. By investigating the database, we identified 63 patients
(0. 38%) who underwent resection of T3 lung cancer invading the diaphragm. These
patients constituted the study population, and their clinical and pathologic
records were retrospectively analyzed. RESULTS: Tumor invasion to the diaphragm
was diagnosed before operation only in 17 patients (27.0%). Complete resections
of the primary lung tumors with the invaded diaphragm were performed in 55
patients (87.3%), of whom 26 had T3 N0 M0 diseases and 29 had T3 Nl-2 M0
diseases. The operative mortality was 1.6% in all patients. The 5-year survival
of patients with complete resection was 22.6%, but there was no 4-year survivor
in patients with incomplete resection (P =.024). The survivals of patients with
completely resected T3 N0 M0 and T3 N1-2 M0 tumors were 28.3% and 18.1%,
respectively (P =.013). In those patients, the depth of diaphragmatic involvement
significantly affected the prognosis. The 5-year survival of the patients with
shallow invasion (parietal pleura or subpleural tissue involvement) was 33.0%,
whereas that of the patients with deep invasion (muscle or peritoneal
infiltration) was 14.3% (P =.036). CONCLUSIONS: In selected patients with lung
carcinoma and diaphragmatic invasion, combined resection of the lung and
diaphragm offers the prospect of cure with acceptable mortality. However, primary
lung tumors with diaphragmatic invasion, especially invasion of the muscle layer
or deeper tissue, are not considered to be T3 lesions, because these cancers are
generally technically resectable but oncologically almost incurable.
PMID- 11003766
TI - Endoscopic coronary artery bypass grafting-the first steps on a long journey.
PMID- 11003767
TI - Closed-chest coronary artery bypass grafting on the beating heart with the use of
a computer-enhanced surgical robotic system.
PMID- 11003768
TI - Closed-chest coronary artery surgery on the beating heart with the use of a
robotic system.
PMID- 11003769
TI - Three-dimensional computed tomographic angiography as preoperative evaluation of
a patent internal thoracic artery graft.
PMID- 11003770
TI - Occult active giant cell aortitis necessitating surgical repair.
PMID- 11003771
TI - Phenoxybenzamine prevents spasm in radial artery conduits for coronary artery
bypass grafting.
PMID- 11003772
TI - Endoluminal replacement of the entire aorta for acute type A aortic dissection in
a patient with Marfan syndrome.
PMID- 11003773
TI - Double-barreled conduit for right atrioventricular connection in tricuspid
atresia: a new technique.
PMID- 11003774
TI - Mitral homograft replacement of tricuspid valve in children.
PMID- 11003775
TI - Rapid enlargement of a distal arch aneurysm after endovascular stent-grafting for
pseudoaneurysm: case report.
PMID- 11003776
TI - Coronary artery bypass grafting without cardiopulmonary bypass in
pheochromocytoma.
PMID- 11003777
TI - Are adenosine myocardial protective effects mediated through cAMP-independent
effects or through cAMP inhibition/production?
PMID- 11003779
TI - S-100beta protein: yet uncertain role as a marker of cerebral injury in cardiac
surgery.
PMID- 11003780
TI - Genetic heterogeneity in hereditary sensory and autonomic neuropathies: The need
for improved ascertainment.
PMID- 11003781
TI - Molecular basis of muscular dystrophies.
AB - Muscular dystrophies represent a heterogeneous group of disorders, which have
been largely classified by clinical phenotype. In the last 10 years,
identification of novel skeletal muscle genes including extracellular matrix,
sarcolemmal, cytoskeletal, cytosolic, and nuclear membrane proteins has changed
the phenotype-based classification and shed new light on the molecular
pathogenesis of these disorders. A large number of genes involved in muscular
dystrophy encode components of the dystrophin-glycoprotein complex (DGC) which
normally links the intracellular cytoskeleton to the extracellular matrix.
Mutations in components of this complex are thought to lead to loss of
sarcolemmal integrity and render muscle fibers more susceptible to damage. Recent
evidence suggests the involvement of vascular smooth muscle DGC in skeletal and
cardiac muscle pathology in some forms of sarcoglycan-deficient limb-girdle
muscular dystrophy. Intriguingly, two other forms of limb-girdle muscular
dystrophy are possibly caused by perturbation of sarcolemma repair mechanisms.
The complete clarification of these various pathways will lead to further
insights into the pathogenesis of this heterogeneous group of muscle disorders.
PMID- 11003782
TI - Electrophysiological features of inherited demyelinating neuropathies: A
reappraisal in the era of molecular diagnosis.
AB - The observation that inherited demyelinating neuropathies have uniform conduction
slowing and that acquired disorders have nonuniform or multifocal slowing was
made prior to the identification of mutations in myelin-specific genes which
cause many of the inherited disorders involving peripheral nerve myelin. It is
now clear that the electrophysiological aspects of these disorders are more
complex than previously realized. Specifically, certain mutations appear to
induce nonuniform slowing of conduction which resemble the findings in acquired
demyelinating neuropathies. It is clinically important to recognize the different
electrodiagnostic patterns of the various inherited demyelinating neuropathies.
In addition, an understanding of the relationship between mutations of specific
genes and their associated neurophysiological findings is likely to facilitate
understanding of the role of these myelin proteins in peripheral nerve function
and of how abnormalities in myelin proteins lead to neuropathy. We therefore
review the current information on the electrophysiological features of the
inherited demyelinating neuropathies in hopes of clarifying their
electrodiagnostic features and to shed light on the physiological consequences of
the different genetic mutations.
PMID- 11003783
TI - Electrodiagnostic studies in amyotrophic lateral sclerosis and other motor neuron
disorders.
AB - The clinical electrodiagnostic medicine (EDX) consultant asked to assess patients
with suspected amyotrophic lateral sclerosis (ALS) has a number of
responsibilities. Among the most important is to provide a clinical assessment in
conjunction with the EDX study. The seriousness of the diagnoses and their
enormous personal and economic impact require a high-quality EDX study based on a
thorough knowledge of and experience with motor neuron diseases (MNDs) and
related disorders. Clinical evaluation will help determine which of the EDX tools
available to the EDX consultant should be applied in individual patients.
Although electromyography (EMG) and nerve conduction study are the most valuable,
each of the following may be helpful in the assessment of selected patients based
on their clinical findings: repetitive nerve stimulation, motor unit number
estimate, single-fiber EMG, somatosensory evoked potential, autonomic function
test, and polysomnography. The pertinent literature on these is reviewed in this
monograph. The selection and application of these EDX tools depend on a thorough
knowledge of the MNDs and related disorders.
PMID- 11003784
TI - Ethical issues in DNA testing.
AB - Molecular tests for single gene disorders have become the "gold standard,"
surpassing in sensitivity and specificity other ancillary tests such as imaging
or neurophysiologic tests. Although direct technical problems are rare for DNA
tests, few outcomes studies have been reported that examine sensitivity,
specificity, and usage of tests outside the setting of academic medical centers.
Ethical problems of DNA testing are mainly discussed in a theoretical framework
and few published studies or case reports deal with real-life situations. Among
neurologists, ethical dilemmas and attempts at their resolution are communicated
mainly on a verbal basis, and even then relatively little follow-up is available.
The potential use of information obtained through DNA testing by other family
members, employers, insurance companies, and governmental agencies deserves
scientific investigation and societal discussion. A major educational effort is
needed to inform patients, providers, and third parties that the presence of a
particular allele in an individual is only one piece in a complex puzzle of
environmental and genetic interactions that may ultimately result in disease.
PMID- 11003785
TI - Phenotypic and genetic study of a family with hereditary sensory neuropathy and
prominent weakness.
AB - We report the clinical and electrophysiological features of six members of a
French family with a dominantly inherited motor and sensory neuropathy. Mean age
at onset was 33.6 +/- 9.1 years. Mean age at examination was 55.5 +/- 13.3 years.
Clinical presentation combined symptoms of hereditary sensory and autonomic
neuropathy type I (HSAN-I) with prominent distal muscle weakness. Five male
patients presented with sensory symptoms involving the distal part of the limbs,
especially the legs. All but one had histories of trophic alterations, consisting
of poorly healing foot ulcers. Muscle weakness and wasting were always present,
often severe, and mainly affected dorsiflexion of the toes and feet. One obligate
female carrier aged 65 was clinically asymptomatic. Electrophysiological findings
were consistent with a distal axonal motor and sensory neuropathy. Results of
linkage analysis excluded the Charcot-Marie-Tooth 2A (CMT2A) and CMT2B loci and
suggested the possibility of a linkage to HSAN-I locus on 9q22.1-q22.3.
PMID- 11003786
TI - Hydrogen peroxide decelerates recovery of action potential after high-frequency
fatigue in skeletal muscle.
AB - Effects of reactive oxygen species (ROS), especially hydrogen peroxide
(H(2)O(2)), on recovery of action potential by resting for 30 min after high
frequency fatigue were studied using frog skeletal muscle fibers. After
stimulation at a frequency of 50 HZ for 2 min, the action potential amplitude was
decreased by 14.5 mV from controls, and resting membrane was depolarized by 15.4
mV. Action potential duration was also prolonged by high-frequency stimulation
(1.5 ms in controls to 2.6 ms). The high-frequency stimulation used here caused
no muscle damage. The action potential was partially improved after a 30-min
rest. Addition of catalase at 500 units/ml or H(2)O(2) at 0.5 mM to sartorius
muscle did not alter any of the parameters of the action potential after high
frequency stimulation. Treatment with catalase accelerated post-fatigue recovery
of the action potential. Application of H(2)O(2) delayed post-fatigue recovery of
resting and action potentials. When added to detubulated toe muscle fibers,
catalase no longer improved the attenuation of action potential induced by high
frequency stimulation, even after a 30-min rest. These findings suggest that
removal of H(2)O(2) from transverse tubules is effective for post-fatigue
recovery of action potential in skeletal muscle.
PMID- 11003787
TI - Comparison of multiple point and statistical motor unit number estimation.
AB - This study compares two common techniques for motor unit number estimation,
multiple point stimulation and statistical method, to determine which is more
reproducible. Surface recorded motor unit action potentials (SMUPs) of the left
hypothenar muscle group were measured on 20 controls and 10 ALS patients. For
multiple point, 10 different threshold SMUPs were recorded. For statistical
method, mean SMUP amplitude was measured at several stimulus levels, typically
spanning >40% of CMAP amplitude range. Both techniques were performed twice,
results averaged, electrodes changed, and all recording repeated. For controls,
mean of two motor unit number estimation (MUNE) (+/- standard deviation) was 60
(+/-5) for statistical method, and 108 (+/-38) for multiple point. For ALS
patients, these values were 21 (+/-16) for statistical method and 55 (+/-39) for
multiple point. Test-retest correlation coefficients and coefficients of
variation for mean of two MUNE were 0.98 and 7% for statistical method, and 0.90
and 12% for multiple point, respectively. Statistical method was more
reproducible and faster than multiple point, supporting its utility in monitoring
rates of MUNE change.
PMID- 11003788
TI - Contractile properties and fatigue of quadriceps muscles in multiple sclerosis.
AB - Functional characteristics of electrically stimulated quadriceps muscles of
patients with multiple sclerosis (MS) were determined to investigate whether
adaptations in muscle properties contribute to the higher fatigability of these
patients. The estimated maximal isometric force generating capacity of MS
patients was only 11.2% (P < 0.05) lower than control subjects. However, the
patients were only able to voluntarily exert 75 +/- 22% (n = 12) of their maximal
capacity, against 94 +/- 6% (n = 7) for the control subjects. There were no
differences in muscle speed, suggesting that muscle fiber distribution was not
different in the MS patients due to reduced muscle usage. During a series of
repeated contractions, greater decrements occurred in isometric force and in
maximal rate of force rise in the MS patients (by 31.3 +/- 10.3% and 50.1 +/-
10.0%, respectively; n = 13) than control subjects (23.8 +/- 6.6% and 39.0 +/-
8.1%, n = 15), suggesting a lower oxidative capacity. The results indicate that
increasing the mass of their muscles by training may help to reduce the excessive
muscle fatigue of MS patients.
PMID- 11003789
TI - Mapping motor cortex projections to single motor units in humans with
transcranial magnetic stimulation.
AB - We devised a method to investigate the cortical organization of
corticomotoneurons (CMs) to upper limb muscles. A spike-triggering technique was
used, in which a tonically discharging single motor unit (SMU) triggered
transcranial magnetic stimulation (TMS) of motor cortex, and the probability of
producing short-latency discharges (primary excitatory responses [PERs]) was
measured. PER probabilities were mapped in 34 SMUs, using a 16 cm(2) scalp grid
with the central reference point having a probability of 0.5. Maps showed a
single optimum point of scalp stimulation and significant decreases in PER
probability with shifts of 2 cm from this point, for all subjects. These findings
suggest that the colony of CMs projecting to an individual SMN is contained
within a small volume of motor cortex. Changes in PER probability with shifts in
stimulation site may reflect the organization of other intracortical neurons
mediating TMS activation of these CMs.
PMID- 11003790
TI - Nuclear accumulation of expanded PABP2 gene product in oculopharyngeal muscular
dystrophy.
AB - Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is an adult-onset
disease caused by (GCG) repeat expansions in exon 1 of the poly(A) binding
protein 2 gene (PABP2). To elucidate the molecular mechanism underlying the
disease, we raised an antiserum against a synthetic peptide fragment predicted
from PABP2 cDNA. The peptide corresponded to amino acids 271-291 where a cluster
of posttranslational arginine methylation occurs. We examined the subcellular
localization of PABP2 in muscle specimens from five patients with OPMD, 14
patients with various neuromuscular disorders, and three normal controls. All
Japanese patients with OPMD have been shown to have expanded (GCG)(8, 9, or 11)
mutations in PABP2, as well as intranuclear tubulofilamentous inclusions (ITFI)
of 8.5 nm. None of 50 separate Japanese control individuals were shown to have
expanded (GCG) repeat in PABP2. Positive immunoreaction for polyclonal PABP2 was
confined to the intranuclear aggregates of muscle fibers exclusively in patients
with OPMD. Frequency of the nuclei positive for PABP2 (2%) was similar to that of
ITFI detected by electron microscopy (2.5%). There was no apparent relationship
between the frequency of PABP2-positive intranuclear aggregates and the severity
of muscle fiber damage. In contrast, nuclear immunoreaction was not detected in
any samples from normal controls or from other neuromuscular diseases. These
results suggest the presence of molecular modification of the product of expanded
(GCG) repeat in PABP2, since the synthetic antigen peptide may not recognize a
highly dimethylated cluster of arginine residues of the native PABP2, but may
recognize the mutated form. Nuclear accumulation of expanded PABP2 product
implies a causative role for ITFI.
PMID- 11003791
TI - Median nerve recovery in carpal tunnel syndrome.
AB - We studied recovery of median nerve function in operated elderly and younger
patients with carpal tunnel syndrome, compared to nonoperated patients, using
neurophysiological methods. Three groups were analyzed separately: elderly
operated (n = 16, aged 70 to 89); younger operated (n = 83, aged 30 to 69); and
nonoperated (n = 52, aged 25 to 83). The elderly operated patients had
significant improvement after surgery in all sensory nerve variables and a
decrease in motor distal latency. The results were comparable to the results in
the younger operated patients. In the nonoperated hands, the same
neurophysiological variables were also significantly improved, but to a lesser
extent than in the operated hands. Overall symptom relief was better in the
operated hands.
PMID- 11003792
TI - Metabolism of rat skeletal muscle after spinal cord transection.
AB - We investigated the energy metabolism of the gastrocnemius muscle of the rat
after spinal cord transection, using in vivo (31)P magnetic resonance
spectroscopy (MRS). Spectra were obtained at rest and during exercise and
recovery before, and at different time-points after, spinal cord transection. At
rest, the adenosine triphosphate (ATP) level was not altered and the
intracellular pH became permanently more alkaline. In electrically stimulated
muscle, cord transection caused a greater phosphocreatine depletion than in
control animals, and the maximum rate of oxidative ATP synthesis was
significantly diminished; at days 30 and 60 after transection, an intracellular
acidification was observed at the end of exercise. These effects indicate that,
as in humans, spinal cord transection in rats leads to a decrease in
mitochondrial oxidative metabolism and probably to an increase in anaerobic
metabolism. This experimental model may prove useful for evaluating various
approaches to improve muscle function in paraplegia.
PMID- 11003793
TI - Clinical and pathologic features of focal myositis.
AB - To clarify the nosology of focal myositis (FM), we report the clinical and
pathologic features of eight patients presenting with focal enlargement of one
muscle. Most patients improved without immunosuppressive therapy, and none
developed polymyositis. Pathologic features were those of an inflammatory
myopathy, with muscle fiber hypertrophy and moderate to severe inflammation. In
most cases, a clustering of tightly packed muscle fibers, enveloped by a thick
bundle of fibrosis, was associated with the diagnosis of FM. Immunohistochemistry
showed T cell predominance within the interstitial infiltrates in all cases. No
evidence of vasculitis was present. Our findings suggest that FM is a benign
condition that has certain clinical features separating it from other
inflammatory myopathies. Pathologic changes, such as large clusters of nesting
muscle fibers surrounded by thick fibrosis, are more characteristic of FM than
polymyositis.
PMID- 11003794
TI - Effects of resistance training on neuromuscular junction morphology.
AB - The aim of this study was to determine the impact of resistance exercise on
neuromuscular junction (NMJ) architecture. Eighteen Sprague-Dawley rats either
participated in a 7-week resistance training program or served as untrained
controls. Following the experimental period, the NMJs of soleus muscles were
visualized with immunofluorescent techniques, and muscle fibers were stained
histochemically. Results indicate that resistance training significantly (P <
0.05) increased endplate perimeter length (15%) and area (16%), and significantly
enhanced the dispersion of acetylcholine receptors within the endplate region.
Pre- and post-synaptic modifications to resistance exercise were well-coupled. No
significant alterations in muscle fiber size or fiber type were detected. The
data presented here indicate that the stimulus of resistance training was
sufficiently potent to remodel NMJ structure, and that this effect cannot be
attributed to muscle fiber hypertrophy or fiber type conversion.
PMID- 11003795
TI - Acquired slow-channel syndrome.
AB - We report the case of a 37-year-old man with clinical and electrophysiological
features of hereditary slow-channel syndrome (SCS) and antibodies against
acetylcholine receptors (AChR-Abs). He presented with weakness of shoulder and
hand muscles. A supramaximal single stimulus to the motor nerves disclosed a
double compound muscle action potential (CMAP). Repetitive stimulation of ulnar,
suprascapular, and median nerves showed a CMAP decrement greater than 10%. The
patient responded to pyridostigmine. This report confirms the importance of AChR
Ab titers in suspected cases of hereditary SCS because patients with positive
AChR-Abs may have a better response to available treatments.
PMID- 11003796
TI - Functional properties of regenerating skeletal muscle following LIF
administration.
AB - We tested the hypothesis that periodic systemic administration of the myogenic
cytokine leukemia inhibitory factor (LIF) enhances the functional recovery of
regenerating skeletal muscle following bupivacaine-induced degeneration. LIF had
no effect on functional capacity or regenerating myofiber size in rat muscles at
7, 14, or 21 days post-injury. The results do not support exogenous
administration of LIF as a treatment for acute muscle injury, but a more frequent
dosing regimen should be tested.
PMID- 11003797
TI - Estimation of cervical cord dysfunction by somatosensory evoked potentials.
AB - The purpose of this study was to examine the relationship of abnormal short
latency somatosensory evoked potentials (SSEPs) recorded by a noncephalic
reference montage with clinical variables in cervical myelopathy patients and to
reexamine the diagnostic utility of SSEPs in such patients. We studied cervical
SSEPs elicited by stimulating the median and ulnar nerves in 87 patients. Our
grade classification of spinal N13, which is based on the normal limits of
latencies or amplitudes, corresponded well with the clinical variables and is of
value when trying to localize the cervical lesion segmentally. The N9-P14
interpeak latency in response to ulnar nerve stimulation correlated well with
lower extremity function (r = -0.440, P <0.0001). We suggest a combined
assessment of N13 amplitude, and N9-N13 and N9-P14 interpeak latencies to
estimate dorsal column and dorsal horn function separately in patients with
cervical myelopathy.
PMID- 11003798
TI - Reproducibility of intracortical inhibition and facilitation using the paired
pulse paradigm.
AB - We have evaluated the reproducibility of intracortical inhibition (ICI) and
facilitation (ICF) studied with paired-pulse focal transcranial magnetic
stimulation. Three investigators studied the same subjects (n = 4) in three
different sessions. A high variability was shown across subjects [coefficient of
variation, (cv) 67.3% for ICI and 21.2% for ICF]. Intersession variability was up
to 37.1% for ICI and 22.7% for ICF. Interinvestigator variability was 17.3% for
ICI and negligible for ICF. Our results may have implications for planning future
studies.
PMID- 11003799
TI - Mild ciguatera poisoning: Case reports with neurophysiological evaluations.
AB - Ciguatera poisoning causes mainly gastrointestinal and neurological effects of
variable severity. However, symptoms of peripheral neuropathy with paresthesias
and paradoxical disturbance of thermal sensation are the hallmark.
Electrophysiological studies are often normal, except in severe cases. We report
four people who developed mild ciguatera poisoning after barracuda ingestion.
Electrophysiological studies documented normocalcemic latent tetany. These
findings are consistent with ciguatoxin's mechanism of toxicity, which involves
inactivation of voltage-gated Na(+) channels and eventually increases nerve
membrane excitability.
PMID- 11003800
TI - Clinicopathological and molecular biological studies in a patient with
neurolymphomatosis.
AB - We describe a patient with a clinical disorder that resembled vasculitic
neuropathy in which peripheral nerves were successively affected over several
months, but without systemic involvement. An initial muscle biopsy near the
involved nerves showed signs of nonspecific inflammation around the muscle and
nerve fibers. Immunosuppressive treatment resulted in a dramatic reduction in
pain, but relapses of the disease eventually occurred, and the patient died 22
months after onset of the first symptoms. Pathologically, a malignant non
Hodgkin's B-cell lymphoma, restricted to the intra- and extradural peripheral
nervous system, was found. The demonstration by Southern blotting of
immunoglobulin heavy chain gene rearrangement confirmed the monoclonal nature of
the lymphomatous cells. In situ hybridization tests for Epstein-Barr and herpes
virus subtypes were negative. Our case underlines i) how difficult diagnosis can
be despite extensive investigations, ii) the usefulness of immunosuppressive
treatment in the early stage of the disease, iii) the importance of
immunostaining and genome analysis for distinguishing between different types of
human neurolymphomatosis, and iv) the fact that the initial inflammatory process
in the muscle biopsy may be interpreted either as a paraneoplastic effect of the
lymphoma or as a viral inflammatory neuromyopathy that triggers the development
of the malignant lymphoma.
PMID- 11003801
TI - Monofocal motor neuropathy responsive to intravenous immunoglobulins.
PMID- 11003803
TI - The anti-reflux barrier and mechanisms of gastro-oesophageal reflux.
AB - The lower oesophageal sphincter (LOS) is the major component of the anti-reflux
barrier. The majority of reflux episodes occur because of intermittent brief
complete lower oesophageal sphincter relaxations, transient LOS relaxations,
rather than from chronic absence of LOS pressure. Recent advances in the
understanding of the neural mechanisms and the receptors involved in the
triggering of transient LOS relaxations have provided new insights into their
control and offer the potential for the development of pharmacological therapy of
reflux based on control of these events. Extrinsic support by the crural
diaphragm is also important and loss of this support through development of
hiatus hernia significantly compromises LOS function. This chapter reviews the
components of the anti-reflux barrier, the patterns and mechanisms of LOS
dysfunction underlying reflux episodes, and the interplay between sphincteric and
non-sphincteric factors.
PMID- 11003804
TI - Mechanisms of oesophageal mucosal defence.
AB - The integrity of the oesophageal mucosa depends upon an equilibrium between
aggressive factors, predominantly acid and pepsin, and protective mechanisms.
Protective mechanisms operate within the oesophageal mucosa as pre-epithelial,
epithelial and post-epithelial defences. Only the protective components of the
oesophageal pre-epithelial defence can be tested in vivo in humans. It has been
recently demonstrated that human oesophageal submucosal glands elaborate mucous
secretion rich in bicarbonate and non-bicarbonate buffers, mucin, prostaglandin
E(2), epidermal growth factor (EGF) and transforming growth factor alpha
(TGFalpha). This oesophageal secretion, accompanied by similarly protective
factors within the swallowed saliva, defines the protective potential of the
oesophageal pre-epithelial defence that exists in the form of a mucus-buffer
layer covering the oesophageal mucosa and which retards the back-diffusion of
hydrogen ions. It has also been demonstrated that patients with severe erosive
reflux oesophagitis exhibit qualitative impairment in both the salivary and
oesophageal components of the oesophageal pre-epithelial defence. Furthermore,
patients with endoscopically negative gastro-oesophageal reflux disease have a
significantly stronger oesophageal pre-epithelial defence than patients with
erosive reflux oesophagitis. On the other hand, African-Americans, who are less
likely to develop erosive reflux oesophagitis, have a stronger oesophageal pre
epithelial defence than do Caucasians. The salivary component of the oesophageal
pre-epithelial defence can be enhanced by mastication and the administration of
cisapride, whereas oesophageal secretion can only be significantly augmented by
cisapride.
PMID- 11003805
TI - Duodenogastro-oesophageal reflux.
AB - The role of duodenogastro-oesophageal reflux (DGOR), once erroneously termed
'bile reflux', in causing oesophageal mucosal damage has been an area of interest
in both animal and human studies. However, due to the lack of appropriate
techniques for accurately measuring DGOR, extrapolation of findings from animal
studies to humans was difficult to make. The recent advent of the Bilitec system,
an ambulatory bilirubin monitoring device, is increasing our knowledge of the
specific role of DGOR in oesophageal diseases. Studies suggest that the DGOR
without acid reflux may result in symptoms but unless acid reflux is present
simultaneously, it does not cause oesophagitis. Therefore, our therapies should
aim at reducing both DGOR and acid reflux. Studies show that this may be
accomplished by anti-reflux surgery or the use of proton pump inhibitors, which,
by reducing gastric volume, decrease the damaging potential of both acid and
DGOR.
PMID- 11003806
TI - Helicobacter pylori infection and gastro-oesophageal reflux disease: coincidence
or association?
AB - Concerning the relationship between Helicobacter pylori infection and gastro
oesophageal reflux disease (GORD), the debate is ongoing whether the infection
confers protection, is harmful or whether both entities are independent.
Epidemiological evidence is given for an increased prevalence of GORD and a
decreased prevalence of H. pylori infection in the western world. The assumpton
derived from it is that H. pylori protects from GORD. Pathophysiological aspects
need to consider the type and expression of gastritis which is associated with
varying changes of gastric function. Depending on the type of gastritis, acid
secretion may either increase or decrease and thereby impact on acid exposure of
the oesophagus. Other changes related to the role of H. pylori in pathophysiology
of GORD are still hypothetical. Clinical data are controversial whether or not
GORD increases after H. pylori eradication. Prospective studies including
characterization of strains and gastric physiology will clarify this issue. An
accelerated induction of gastric mucosal atrophy in patients on long-term proton
pump inhibitors is reported in most available studies. An increase of
inflammatory activity in fundic and corpus mucosa is a consistent phenomenon.
Therefore, in the authors' opinion, eradication appears advisable.
PMID- 11003807
TI - Epidemiology and natural history of reflux disease.
AB - Gastro-oesophageal reflux disease (GORD) is a highly prevalent condition in
Western countries; at least 20% of the population have weekly symptoms. The
incidence appears to be rising in the West and in some developing countries.
Heartburn, based on a carefully elicited history, is reasonably specific for
identifying GORD if it is a predominant complaint. Symptoms, however, appear to
correlate poorly with oesophagitis; hence, severe symptoms do not indicate there
is greater oesophageal damage. Only one-third to one-half of patients with GORD
undergoing endoscopy have oesophagitis. GORD is usually a chronic disease but one
third may lose their symptoms over time. An ill-defined subset of patients over
time may progress to develop abnormal acid exposure or oesophagitis, or both,
when none existed at baseline. GORD has a significant negative impact on quality
of life to the same degree as other chronic medical conditions, but impairment in
quality of life is independent of oesophagitis.
PMID- 11003808
TI - Diagnosis of reflux disease.
AB - There are numerous tests for which a diagnostic value in the context of gastro
oesophageal reflux disease has been claimed. Some of these tests (e.g. the acid
perfusion test) have become obsolete after the advent of 24-hour oesophageal pH
monitoring. With the latter test not only can excessive reflux be identified, but
also, and more importantly, a temporal relationship can be demonstrated between a
patient's symptoms and reflux episodes. Radiographical examination of the
oesophagus has largely been replaced by endoscopy, although the use of the former
test is still indicated in certain circumstances (e.g. in the differentiation of
sliding from para-oesophageal hiatus hernia). In clinical practice, the so-called
proton pump inhibitor test has gained considerable popularity. Despite several
studies on the specificity and sensitivity of this test, its value has not yet
been established with sufficient accuracy. Conventional manometric evaluation of
lower oesophageal sphincter pressure has been over-emphasized as a diagnostic
test in gastro-oesophageal reflux disease.
PMID- 11003809
TI - Strategies for medical management of reflux disease.
AB - Management of gastro-oesophageal reflux disease (GORD) patients must consider two
issues: (i) how to optimize the treatment of a presenting symptom complex, and
(ii) how to manage risk of adenocarcinoma associated with GORD. In most cases the
need for, and potency of, pharmacological therapy used is decided by symptom
assessment. Considering cost effectiveness, the three increments of
pharmacological therapy are: (i) generic histamine(2)receptor antagonists, (ii)
standard dose proton pump inhibitors, and (iii) higher dose proton pump
inhibitors. Endoscopy is warranted if there is doubt regarding the diagnosis of
GORD or if the patient relays alarm symptoms suggesting more ominous diagnoses
(dysphagia, bleeding, weight loss, odynophagia). The other major indication for
endoscopy is to screen for adenocarcinoma or Barrett's metaplasia in the patient
with chronic symptoms. In most patients, the need for maintenance medical therapy
is determined by the rapidity of symptom recurrence during a trial period off the
medication.
PMID- 11003810
TI - Anti-reflux surgery in the laparoscopic era.
AB - The introduction of laparoscopic anti-reflux surgery has led to a renewed
interest in the operative treatment of gastro-oesophageal reflux disease (GORD).
Three groups of patients can be identified who are particularly suited to
laparoscopic anti-reflux surgery. Failure to respond to medical treatment has
been historically the main determinant for those referred for anti-reflux
surgery. With the availability of modern anti-secretory drugs most patients with
chronic GORD can control their symptoms adequately by these means. Even effective
medical therapy, however, is not without problems. In many patients rapid and
consistent relapse of symptoms and oesophagitis occurs on cessation of therapy.
Some of these patients do not want to be reliant on a form of medication that has
yet to firmly establish its record for safety over many years of continued use. A
second readily identifiable group of patients are those who are often described
as 'volume refluxers'. They are bothered by persistent fluid regurgitation
despite adequate control of their heartburn with acid suppressive drugs. Third
there are those individuals who develop oesophageal strictures and those with
Barrett's oesophagus and concomitant reflux symptoms and also those with
respiratory complications associated with presumed aspiration of gastric juice
into the pharynx and into the respiratory tree. The low morbidity associated with
laparoscopic surgery that has been achieved in the best modern series means that
the pendulum may swing back to surgery and therefore it is even more important
that the right operation (fundoplication) is done for the right patient. Failure
to create an adequate crural repair behind the wrap is associated with a risk of
early post-operative para-oesophageal herniation and proximal wrap migration. The
question of tailored anti-reflux surgery based on the pre-operative motor
function of the body of the oesophagus is widely applied, although the scientific
basis for these selective approaches is rather weak. Partial fundoplication seems
to be associated with very low rates of dysphagia and of gas bloat. Assessment of
the post-operative result should ideally be done by an independent observer and
should consider not only traditional outcome measures but also the impact of
surgery on the quality of the patient's life. Investigations on the cost
effectiveness of these surgical therapeutic strategies suggest important benefits
of surgery, which should be incorporated into the clinical decision process when
assessing different long-term management alternatives for patients with chronic
GORD.
PMID- 11003811
TI - Controversies in long-term management of reflux disease.
AB - There are significant controversies about the long-term therapy of reflux disease
that arise primarily from a lack of data on the risks of the disease and its
therapies over the relevant time scale of several decades. Currently, there are
no appropriately structured direct comparisons between the two current major
treatment options of tailored long-term acid suppression and laparoscopic anti
reflux surgery. Critical review of the available literature does not support the
assertion that anti-reflux surgery has a superior risk/benefit profile when
compared to long-term proton pump inhibitor (PPI) therapy, since non-controlled
data indicate that although both therapies are relatively safe, morbidity and
mortality rates are lowest with PPI therapy, whilst efficacy is comparable. The
clinical significance of the reflux that continues to occur after both anti
reflux surgery and during PPI therapy is uncertain, but probably over-estimated.
As pathological duodenogastro-oesophageal reflux affects only a small minority of
reflux disease patients, issues arising from it should not be regarded as
mainstream influences on the choice of long-term therapy. Notwithstanding, this
type of reflux is substantially reduced by both PPI therapy and anti-reflux
surgery. The choice between laparoscopic surgery and long-term tailored acid
suppression should be determined primarily by assessment of operative risk, the
quality of surgery available to the patient and by patient preference, after
balanced explanation of the risks and benefits of each option. Given that the
cost of PPI therapy is likely to drop substantially in the next few years, drug
cost should not be a major pressure for the choice of anti-reflux surgery.
PMID- 11003812
TI - Endoscopy-negative reflux disease.
AB - The majority of patients with symptoms of gastro-oesophageal reflux have no
endoscopic evidence of oesophagitis. There has been remarkably little systematic
gathering of information about this group of patients. It is commonly believed
that they have a mild form of reflux disease, with low levels of dysfunction that
usually respond to simple therapeutic measures. Emerging data from recent studies
indicate that this is not the case. Endoscopy-negative patients have symptom
severities comparable to those with erosive disease, and which significantly
impair their quality of life. The limited data available on the pathophysiology
of endoscopy-negative reflux disease suggest that, in the majority of patients,
it is as much a disease of excessive gastro-oesophageal reflux as it is in
patients with oesophageal lesions. The same principles that apply to successful
treatment in patients with oesophagitis also hold true for patients with
endoscopy-negative disease.
PMID- 11003813
TI - Reflux in children.
AB - Gastro-oesophageal reflux (GOR) is an extremely common paediatric problem that
often runs a harmless and self-limited course. Physiological GOR however can lead
to marked parental anxiety, many unnecessary investigations and often unwarranted
and potentially harmful therapeutic interventions. Our ability to better define
GOR and gastro-oesophageal reflux disease (GORD) has improved in the past 15
years with a better understanding of the pathophysiology in infants and children
due to the development and wider use of flexible endoscopy, 24-hour oesophageal
pH monitoring and, more recently, the use of micromanometric methods for studying
oesophageal motility. This will be further enhanced in the future with the
development of non-invasive breath testing to study gastrointestinal motility and
the use of electrical impedance to study fluid movement. Our therapeutic
interventions have also improved particularly in the areas of acid suppression,
improved surgical techniques and most recently laparoscopic fundoplication. This
chapter reviews these advances in the paediatric area especially with regard to
pathophysiology, diagnostic testing and therapeutic intervention.
PMID- 11003815
TI - Index
PMID- 11003814
TI - Barrett's oesophagus: diagnosis and management.
AB - Gastro-oesophageal reflux disease and its sequela, Barrett's oesophagus, are the
major recognized risk factors for oesophageal adenocarcinoma, a tumour whose
frequency has increased dramatically in Western countries over the past few
decades. Barrett's oesophagus develops through the process of metaplasia in which
one adult cell type replaces another. The metaplastic, intestinal-type cells of
Barrett's oesophagus are predisposed to develop genetic changes that eventuate in
cancer. This report reviews the recent controversy regarding diagnostic criteria
for Barrett's oesophagus, and provides practical guidelines for identifying the
condition. The risks and benefits of the proposed medical, surgical and
endoscopic therapies for Barrett's oesophagus are discussed in detail, and the
approach to management recently endorsed by the American College of
Gastroenterology is summarized.
PMID- 11003816
TI - Preface
PMID- 11003817
TI - What it takes to fly: the structural and functional respiratory refinements in
birds and bats.
AB - In absolute terms, flight is a highly energetically expensive form of locomotion.
However, with respect to its cost per unit distance covered, powered flight is a
very efficient mode of transport. Birds and bats are the only extant vertebrate
taxa that have achieved flight. Phylogenetically different, they independently
accomplished this elite mode of locomotion by employing diverse adaptive schemes
and strategies. Integration of functional and structural parameters, a
transaction that resulted in certain trade-offs and compromises, was used to
overcome exacting constraints. Unique morphological, physiological and
biochemical properties were initiated and refined to enhance the uptake, transfer
and utilization of oxygen for high aerobic capacities. In bats, exquisite
pulmonary structural parameters were combined with optimal haematological ones: a
thin blood-gas barrier, a large pulmonary capillary blood volume and a remarkably
extensive alveolar surface area in certain species developed in a remarkably
large lung. These factors were augmented by, for example, exceptionally high
venous haematocrits and haemoglobin concentrations. In birds, a particularly
large respiratory surface area and a remarkably thin blood-gas (tissue) barrier
developed in a small, rigid lung; a highly efficient cross-current system was
fabricated within the parabronchi. The development of flight in only four animal
taxa (among all the animal groups that have ever evolved; i.e. insects, the now
extinct pterosaurs, birds and bats) provides evidence for the enormous
biophysical and energetic constraints that have stymied volancy. Bats improved a
fundamentally mammalian lung to procure the large amounts of oxygen needed for
flight. The lung/air sac system of birds is not therefore a prescriptive
morphology for flight: the essence of its design can be found in the evolution of
the reptilian lung, the immediate progenitor stock from which birds arose. The
attainment of flight is a classic paradigm of the remarkable adaptability
inherent in organismal and organic biology for countering selective pressures by
initiating elegant morphologies and physiologies.
PMID- 11003818
TI - Immunolocalization of Dpfp1, a byssal protein of the zebra mussel Dreissena
polymorpha.
AB - The zebra mussel is one of only a few freshwater bivalves known to produce a
byssus. This fibrous, proteinaceous and highly cross-linked structure allows the
mussel to attach to a variety of substrata and contributes to its notoriety as a
major freshwater biofouling species. We have successfully expressed a full-length
version of Dreissena polymorpha foot protein 1 (Dpfp1), a putative byssal thread
precursor, and have used the recombinant protein as an antigen for polyclonal
antibody production. Antisera obtained from rabbits immunized with recombinant
Dpfp1 recognize the protein in western blots of extracts from foot tissue and
byssal threads. On the basis of this evidence, we conclude that Dpfp1 is a byssal
precursor protein manufactured and stored in the foot of the mussel.
Immunohistochemical localization of Dpfp1 suggests that the protein is localized
in secretory granules in a large gland surrounding the ventral groove of the
foot. Only a subset of these glandular cells stockpiles the protein, implying
that the zebra mussel foot is a complex organ capable of several distinct
secretory activities involved in byssal thread formation. The uniform
distribution of Dpfp1-containing cells suggests that the protein is a significant
load-bearing component of zebra mussel byssal threads, although a more rigorous
test of this hypothesis awaits ultrastructural localization of the protein in
mature byssal threads.
PMID- 11003819
TI - Ontogenetic changes in characteristics required for endothermy in juvenile black
skipjack tuna (Euthynnus lineatus).
AB - To characterize better the development of endothermy in tunas, we assessed how
the abilities to generate heat and to conserve heat within the aerobic, slow
twitch (red) myotomal muscle using counter-current heat exchangers (retia) change
with size in juvenile black skipjack tuna (Euthynnus lineatus) above and below
the hypothesized minimum size for endothermy of 207 mm fork length (FL). Early
juvenile scombrids (10-77 mm FL) collected off the Pacific coast of Panama were
raised to larger sizes at the Inter-American Tropical Tuna Commission Laboratory
at Achotines Bay, Panama. Evidence of central and lateral rete blood vessels was
found in E. lineatus as small as 95.9 mm FL and 125 mm FL, respectively. In
larger E. lineatus juveniles (up to 244 mm FL), the capacity for heat exchange
increased with fork length as a result of increases in rete length, rete width
and the number of vessel rows. The amount (g) of red muscle increased
exponentially with fork length in both E. lineatus (105-255 mm FL) and a closely
related ectothermic species, the sierra Spanish mackerel Scomberomorus sierra
(151-212 mm FL), but was greater in E. lineatus at a given fork length. The
specific activity (international units g(-)(1)) of the enzyme citrate synthase in
red muscle, an index of tissue heat production potential, increased slightly with
fork length in juvenile E. lineatus (84. 1-180 mm FL) and S. sierra (122-215 mm
FL). Thus, total red muscle heat production capacity (red muscle citrate synthase
activity per gram times red muscle mass in grams) increased with fork length,
primarily because of the increase in red muscle mass. Below 95.9 mm FL, E.
lineatus cannot maintain red muscle temperature (T(m)) above the ambient water
temperature (T(a)) because juveniles of this size lack retia. Above 95.9 mm FL,
the relationship between T(x) (T(m)-T(a)) and FL for E. lineatus diverges from
that for the ectothermic S. sierra because of increases in the capacities for
both heat production and heat retention that result in the development of
endothermy.
PMID- 11003820
TI - Maximum sustainable speeds and cost of swimming in juvenile kawakawa tuna
(Euthynnus affinis) and chub mackerel (Scomber japonicus).
AB - Tunas (Scombridae) have been assumed to be among the fastest and most efficient
swimmers because they elevate the temperature of the slow-twitch, aerobic
locomotor muscle above the ambient water temperature (endothermy) and because of
their streamlined body shape and use of the thunniform locomotor mode. The
purpose of this study was to test the hypothesis that juvenile tunas swim both
faster and more efficiently than their ectothermic relatives. The maximum
sustainable swimming speed (U(max), the maximum speed attained while using a
steady, continuous gait powered by the aerobic myotomal muscle) and the net cost
of transport (COT(net)) were compared at 24 degrees C in similar-sized (116-255
mm fork length) juvenile scombrids, an endothermic tuna, the kawakawa (Euthynnus
affinis) and the ectothermic chub mackerel (Scomber japonicus). U(max) and
COT(net) were measured by forcing individual fish to swim in a temperature
controlled, variable-speed swimming tunnel respirometer. There were no
significant interspecific differences in the relationship between U(max) and body
mass or fork length or in the relationship between COT(net) and body mass or fork
length. Muscle temperatures were elevated by 1.0-2.3 degrees C and 0.1-0.6
degrees C above water temperature in the kawakawa and chub mackerel,
respectively. The juvenile kawakawa had significantly higher standard metabolic
rates than the chub mackerel, because the total rate of oxygen consumption at a
given swimming speed was higher in the kawakawa when the effects of fish size
were accounted for. Thus, juvenile kawakawa are not capable of higher sustainable
swimming speeds and are not more efficient swimmers than juvenile chub mackerel.
PMID- 11003821
TI - Swimming kinematics of juvenile kawakawa tuna (Euthynnus affinis) and chub
mackerel (Scomber japonicus).
AB - The swimming kinematics of two active pelagic fishes from the family Scombridae
were compared to test the hypothesis that the kawakawa tuna (Euthynnus affinis)
uses the thunniform mode of locomotion, in which the body is held more rigid and
undergoes less lateral movement in comparison with the chub mackerel (Scomber
japonicus), which uses the carangiform swimming mode. This study, the first
quantitative kinematic comparison of size-matched scombrids, confirmed
significantly different swimming kinematics in the two species. Ten kawakawa
(15.1-25.5 cm fork length, FL) and eight chub mackerel (14.0-23.4 cm FL), all
juveniles, were videotaped at 120 Hz while swimming at several speeds up to their
maximum sustained speed at 24 degrees C. Computerized motion analysis was used to
digitize specific points on the body in sequential video frames, and kinematic
variables were quantified from the progression of the points over time. At a
given speed, kawakawa displayed a significantly greater tailbeat frequency, but
lower stride length, tailbeat amplitude and propulsive wavelength, than chub
mackerel when size effects were accounted for. Midline curvatures subdivided on
the basis of X-rays into individual vertebral elements were used to quantify
axial bending in a subset of the fish studied. Maximum intervertebral lateral
displacement and intervertebral flexion angles were significantly lower along
most of the body in kawakawa than in chub mackerel, indicating that the kawakawa
undergoes less axial flexion than does the chub mackerel, resulting in lower
tailbeat amplitudes. However, lateral movement at the tip of the snout, or yaw,
did not differ significantly interspecifically. Despite these differences, the
net cost of transport was the same in the two species, and the total cost was
higher in the kawakawa, indicating that the tuna juveniles are not more efficient
swimmers.
PMID- 11003822
TI - Effects of feeding on arterial blood gases in the American alligator Alligator
mississippiensis.
AB - Reptiles habitually ingest large meals at infrequent intervals, leading to
changes in acid-base status as the net secretion of acid to the stomach causes a
metabolic alkalosis (the alkaline tide). In chronically cannulated and
undisturbed amphibians and reptiles, the pH changes in arterial blood are,
nevertheless, reduced by a concomitant respiratory acidosis (increased P(CO2)
caused by a relative hypoventilation). Alligators (Alligator mississippiensis)
have been reported to exhibit exceptionally large increases in plasma [HCO3(-)]
following feeding, but these studies were based on blood samples obtained by
cardiac puncture, so stress and disturbance may have affected the blood gas
levels. Furthermore, crocodilian haemoglobin is characterised by a unique binding
of HCO3(-) that act to reduce blood oxygen-affinity, and it has been proposed
that this feature safeguards oxygen offloading by counteracting pH effects on
blood oxygen-affinity. Therefore, to study acid-base regulation and the
interaction between the alkaline tide and oxygen transport in more detail, we
describe the arterial blood gas composition of chronically cannulated and
undisturbed alligators before and after voluntary feeding (meal size 7.5+/-1% of
body mass). Digestion was associated with an approximately fourfold increase in
metabolic rate (from 0.63+/-0.04 to 2.32+/-0.24 ml O(2) min(-1)kg(-1)) and was
accompanied by a small increase in the respiratory gas exchange ratio. The
arterial P(O2) of fasting alligators was 60.3+/-6.8 mmHg (1 mmHg = 0.133 kPa) and
reached a maximum of 81.3+/-2.7 mmHg at 96 h following feeding; there was only a
small increase in lactate levels, so the increased metabolic rate seems to be
entirely aerobic. Plasma [HCO3(-)] increased from 24.4+/-1.1 to 36.9+/-1.7 mmol
l(-1) (at 24 h), but since arterial P(CO2) increased from 29.0+/-1.1 to 36.8+/
1.3 mmHg, arterial pH remained virtually unaffected (changing from 7.51+/-0.01 to
7.58+/-0.01 at 24 h). The changes in plasma [HCO3(-)] were mirrored by equimolar
reductions in plasma [Cl(-)]. The in vitro blood oxygen-affinity was reduced
during the post-prandial period, whereas the estimated in vivo blood oxygen
affinity remained virtually constant. This supports the view that the specific
HCO3(-) effect prevents an increased blood oxygen-affinity during digestion in
alligators.
PMID- 11003823
TI - Aerodynamic characteristics of dragonfly wing sections compared with technical
aerofoils.
AB - During gliding, dragonfly wings can be interpreted as acting as ultra-light
aerofoils which, for static reasons, have a well-defined cross-sectional
corrugation. This corrugation forms profile valleys in which rotating vortices
develop. The cross-sectional configuration varies greatly along the longitudinal
axis of the wing. This produces different local aerodynamic characteristics.
Analyses of the C(L)/C(D) characteristics, where C(L) and C(D) are the lift and
drag coefficients, respectively (at Reynolds numbers Re of 7880 and 10 000),
using a force balance system, have shown that all cross-sectional geometries have
very low drag coefficients (C(D, min)<0.06) closely resembling those of flat
plates. However, the wing profiles, depending upon their position along the span
length, attain much higher lift values than flat plates. The orientation of the
leading edge does not play an important role. The detectable lift forces can be
compared with those of technical wing profiles for low Re numbers. Pressure
measurements (at Re=9300) show that, because of rotating vortices along the chord
length, not only is the effective profile form changed, but the pressure
relationship on the profile is also changed. Irrespective of the side of the
profile, negative pressure is produced in the profile valleys, and net negative
pressure on the upper side of the profile is reached only at angles of attack
greater than 0 degrees. These results demonstrate the importance of careful
geometrical synchronisation as an answer to the static and aerodynamic demands
placed upon the ultra-light aerofoils of a dragonfly.
PMID- 11003824
TI - Sanderlings (Calidris alba) have a magnetic compass: orientation experiments
during spring migration in Iceland.
AB - The migratory orientation of sanderlings (Calidris alba) was investigated with
cage experiments during the spring migration in southwest Iceland. Sanderlings
were exposed to 90 degrees counterclockwise-shifted magnetic fields under both
clear skies and natural overcast. Clear sky control tests resulted in a northerly
mean direction, in agreement with predictions based on ringing recovery data and
earlier visual observations of departing flocks. Sanderlings closely followed
experimental deflections of magnetic fields when tested under clear skies.
Control experiments under natural overcast resulted in a bimodal distribution
approximately coinciding with the magnetic north-south axis. Overcast tests did
not reveal any predictable response to the experimental treatment, but instead
resulted in a non-significant circular distribution. The time of orientation
experiments in relation to the tidal cycle affects the motivation of the birds to
depart, as shown by the lower directional scatter of headings of individuals
tested within the appropriate tidal window under clear skies. Sanderlings were
significantly more likely to become inactive under overcast conditions than under
clear sky conditions. The results demonstrate, for the first time, that a wader
species such as the sanderling possesses a magnetic compass and suggest that
magnetic cues are of primary directional importance. However, overcast
experiments indicate that both celestial and geomagnetic information are needed
for sanderlings to realize a seasonally appropriate migratory orientation.
PMID- 11003825
TI - Sustaining olfaction at low salinities: mapping ion flux associated with the
olfactory sensilla of the blue crab Callinectes sapidus.
AB - To test the hypothesis of a diffusion-generated, ionic/osmotic microenvironment
within the olfactory sensilla (aesthetascs), flux gradients of Ca(2+) and K(+)
associated with the external surfaces of these sensilla were spatially mapped
using self-referencing, ion-selective microelectrodes. Blue crabs (Callinectes
sapidus) acclimated to low-salinity conditions (15% sea water and fresh water)
showed a net efflux of ions from the aesthetascs. The region of maximum flux
associated with each aesthetasc conformed to that predicted from structural data
and corresponded to the permeable region of the cuticle separating the olfactory
dendrites from the external environment. Estimates of net flux from the entire
tuft of aesthetascs for both Ca(2+) and K(+) fell within the predicted range on
the basis of comparisons with (22)Na(+) flux measured previously and assuming a
passive diffusion model of ion movement from the hemolymph to the sensillar lymph
and, ultimately, to the external environment. The maximum concentrations of these
ions measured deep within the tuft are discussed in the light of a potential
across the aesthetascs that may limit ion efflux at low salinities.
PMID- 11003826
TI - Flexibility in basal metabolic rate and evaporative water loss among hoopoe larks
exposed to different environmental temperatures.
AB - The 'energy demand' hypothesis for short-term adjustments in basal metabolic rate
(BMR) posits that birds adjust the size of their internal organs relative to food
intake, a correlate of energy demand. We tested this hypothesis on hoopoe larks
(Alaemon alaudipes), inhabitants of the Arabian desert, by acclimating birds for
3 weeks at 15 degrees C and at 36 degrees C, then measuring their BMR and total
evaporative water loss (TEWL). Thereafter, we determined the dry masses of their
brain, heart, liver, kidney, stomach, intestine and muscles of the pectoral
region. Although mean body mass did not differ initially between the two groups,
after 3 weeks, birds in the 15 degrees C group had gained mass (44.1+/-6.5 g),
whereas larks in the 36 degrees C group had maintained a constant mass (36.6+/
3.6 g; means +/- s.d., N=6). Birds in the 15 degrees C group had a mean BMR of
46.8+/-6.9 kJ day(-1), whereas birds in the 36 degrees C group had a BMR of
32.9+/-6.3 kJ day(-1), values that were significantly different when we
controlled for differences in body mass. When measured at 35 degrees C, larks in
the cold-exposure group had a TEWL of 3.55+/-0.60 g H(2)O day(-)(1), whereas TEWL
for birds in the 36 degrees C group averaged 2.23+/-0.28 g H(2)O day(-1), a
difference of 59.2%. Mass-independent TEWL differed significantly between groups.
Larks in the 15 degrees C group had a significantly larger liver, kidney and
intestine than larks in the 36 degrees C group. The total increase in organ mass
contributed 14.3% towards the total mass increment in the cold exposure group.
Increased food intake among larks in the cold group apparently resulted in
enlargement of some of the internal organs, and the increase in mass of these
organs required a higher rate of oxygen uptake to support them. As oxygen demands
increased, larks apparently lost more evaporative water, but the relationship
between increases in BMR and TEWL remains unresolved.
PMID- 11003827
TI - Crushing motor patterns in drum (Teleostei: Sciaenidae): functional novelties
associated with molluscivory.
AB - This study explores the evolution of molluscivory in the marine teleost family
Sciaenidae by comparing the motor activity patterns of the pharyngeal muscles of
two closely related taxa, the molluscivorous black drum (Pogonias cromis) and the
generalist red drum (Sciaenops ocellatus). Muscle activity patterns were recorded
simultaneously from eight pharyngeal muscles. Electromyographic (EMG) activity
was recorded during feeding on three prey types that varied in shell hardness.
Canonical variate and discriminant function analyses were used to describe the
distinctness of drum pharyngeal processing behaviors. Discriminant functions
built of EMG timing variables were more accurate than muscle activity intensity
at identifying cycles by prey type and species. Both drum species demonstrated
the ability to modulate pharyngeal motor patterns in response to prey hardness.
The mean motor patterns and the canonical variate space of crushing behavior
indicated that black drum employed a novel motor pattern during molluscivory. The
mollusc-crushing motor pattern of black drum is different from other neoteleost
pharyngeal behaviors in lacking upper jaw retraction by the retractor dorsalis
muscle. This functional modification suggests that crushing hard-shelled marine
bivalves requires a 'vice-like' compression bite in contrast to the shearing
forces that are applied to weaker-shelled fiddler crabs by red drum and to
freshwater snails by redear sunfish.
PMID- 11003828
TI - Ventilatory and metabolic responses to hypoxia and sulphide in the lugworm
Arenicola marina (L.).
AB - We examined the effects of hypoxia and sulphide levels on the ventilatory
activity of Arenicola marina and determined whether ventilation compensates for
oxygen deficiency and affects the mode of energy provision. A. marina ventilated
intermittently, irrespective of ambient P(O2) and sulphide concentration. The
ventilation rate was 28.5+/-16 ml h(-1) g(-1) wet mass during normoxia, but
increased to 175+/-60% of this value during moderate hypoxia, during which
aerobic energy metabolism was maintained. Below a P(O2) of 6.2 kPa, A. marina
reduced the ventilated volume to 54+/-16% of the normoxic value and became
anaerobic, as indicated by the accumulation of succinate and strombine.
Incubation with 27 micromol l(-1) ambient sulphide had no effect on the normoxic
and hypoxic ventilation rates or on the P(O2) below which anaerobiosis started
(P(cM)). Increased sulphide concentrations reduced the ventilation rate and
shifted the P(cM) towards a higher P(O2) below 10.7 kPa. Sulphide diffused into
the body and was at least partially detoxified to thiosulphate when oxygen was
present. Under normoxia, sulphide accumulated in the body wall tissue and
coelomic fluid when ambient sulphide levels exceeded 117 micromol l(-1) and 216
micromol l(-1), respectively. A decrease in P(O2) in the presence of 27 or 117
micromol l(-1) ambient sulphide had no significant effect on sulphide
accumulation.
PMID- 11003829
TI - K(+) currents in cultured neurones from a polyclad flatworm.
AB - Cells from the brain of the polyclad flatworm Notoplana atomata were dispersed
and maintained in primary culture for up to 3 weeks. Whole-cell patch-clamp of
presumed neurones revealed outwardly directed K(+) currents that comprised, in
varying proportions, a rapidly activating (time constant tau =0.94+/-0.79 ms;
N=15) and inactivating ( tau =26.1+/-1.9 ms; N=22) current and a second current
that also activated rapidly ( tau =1.1+/-0.2 ms; N=9) (means +/- s.e.m.) but did
not inactivate within 100 ms. Both current types activated over similar voltage
ranges. Activation and steady-state inactivation overlap and are markedly
rightward-shifted compared with most Shaker-like currents (half-activation of
16.9+/-1. 9 mV, N=7, half-inactivation of -35.4+/-3.0 mV, N=5). Recovery from
inactivation was rapid (50+/-2.5 ms at -90 mV). Both currents were unaffected by
tetraethylammonium (25 mmol l(-1)), whereas 4-aminopyridine (10 mmol l(-1))
selectively blocked the inactivating current. The rapidly inactivating current,
like cloned K(+) channels from cnidarians and certain cloned K(+) channels from
molluscs and the Kv3 family of vertebrate channels, differed from most A-type
K(+) currents reported to date. These findings suggest that K(+) currents in
Notoplana atomata play novel roles in shaping excitability properties.
PMID- 11003830
TI - The mechanisms of urea transport by early life stages of rainbow trout
(Oncorhynchus mykiss).
AB - We tested the hypothesis that urea transport in rainbow trout (Oncorhynchus
mykiss) embryos is dependent, in part, on a bidirectional urea-transport protein.
Acute exposure to phloretin and urea analogs [acetamide, thiourea, 1,(4
nitrophenyl)-2-thiourea] reversibly inhibited urea excretion from the embryos to
the external water. Unidirectional urea influx was inhibited by acetamide and
thiourea, with IC(50) values of 0.04 and 0.05 mmol l(-1), respectively. Influx of
urea from the external water to the embryo tended to saturate at elevated
external urea concentrations (V(max)=10.50 nmol g(-1) h(-1); K(m)=2 mmol l(-1)).
At very high urea concentrations (20 mmol l(-1)), however, a second, non
saturable component was apparent. These results indicate that urea excretion in
trout embryos is dependent, in part, on a phloretin-sensitive facilitated urea
transporter similar to that reported in mammalian inner medullary collecting
ducts and elasmobranch kidney.
PMID- 11003831
TI - Hhex and scl function in parallel to regulate early endothelial and blood
differentiation in zebrafish.
AB - During embryogenesis, endothelial and blood precursors are hypothesized to arise
from a common progenitor, the hemangioblast. Several genes that affect the
differentiation of, or are expressed early in, both the endothelial and blood
lineages may in fact function at the level of the hemangioblast. For example, the
zebrafish cloche mutation disrupts the differentiation of both endothelial and
blood cells. The transcription factor gene scl is expressed in both endothelial
and blood lineages from an early stage and can regulate their differentiation.
Here we report that in zebrafish the homeobox gene hhex (previously called hex)
is also expressed in endothelial and blood lineages from an early stage. We find
that hhex expression in these lineages is significantly reduced in cloche mutant
embryos, indicating that hhex functions downstream of cloche to regulate
endothelial and blood differentiation. Ectopic expression of hhex through
injection of a DNA construct leads to the premature and ectopic expression of
early endothelial and blood differentiation genes such as fli1, flk1 and gata1,
indicating that Hhex can positively regulate endothelial and blood
differentiation. However, analysis of a hhex deficiency allele shows that hhex is
not essential for early endothelial and blood differentiation, suggesting that
another gene, perhaps scl, compensates for the absence of Hhex function.
Furthermore, we find that hhex and scl can induce each other's expression,
suggesting that these two genes cross-regulate each other during early
endothelial and blood differentiation. Together, these data provide the initial
framework of a pathway that can be used to further integrate the molecular events
regulating hemangioblast differentiation.
PMID- 11003832
TI - Requirements of Lim1, a Drosophila LIM-homeobox gene, for normal leg and antennal
development.
AB - During Drosophila leg development, the distal-most compartment (pretarsus) and
its immediate neighbour (tarsal segment 5) are specified by a pretarsus-specific
homeobox gene, aristaless, and tarsal-segment-specific Bar homeobox genes,
respectively; the pretarsus/tarsal-segment boundary is formed by antagonistic
interactions between Bar and pretarsus-specific genes that include aristaless
(Kojima, T., Sato, M. and Saigo, K. (2000) Development 127, 769-778). Here, we
show that Drosophila Lim1, a homologue of vertebrate Lim1 encoding a LIM
homeodomain protein, is involved in pretarsus specification and boundary
formation through its activation of aristaless. Ectopic expression of Lim1 caused
aristaless misexpression, while aristaless expression was significantly reduced
in Lim1-null mutant clones. Pretarsus Lim1 expression was negatively regulated by
Bar and abolished in leg discs lacking aristaless activity, which was associated
with strong Bar misexpression in the presumptive pretarsus. No Lim1 misexpression
occurred upon aristaless misexpression. The concerted function of Lim1 and
aristaless was required to maintain Fasciclin 2 expression in border cells and
form a smooth pretarsus/tarsal-segment boundary. Lim1 was also required for
femur, coxa and antennal development.
PMID- 11003833
TI - Spatial specification of mammalian eye territories by reciprocal transcriptional
repression of Pax2 and Pax6.
AB - We have studied the molecular basis of the Pax2 and Pax6 function in the
establishment of visual system territories. Loss-of-function mutants have
revealed crucial roles for Pax2 in the generation of the optic stalk and for Pax6
in the development of the optic cup. Ectopic expression of Pax6 in the optic
stalk under control of Pax2 promoter elements resulted in a shift of the optic
cup/optic stalk boundary indicated by the presence of retinal pigmented cells on
the optic stalk. By studying mouse embryos at early developmental stages we
detected an expansion of Pax2 expression domain in the Pax6(-/-) mutant and of
Pax6 expression domain in the Pax2(-/-) embryo. These results suggest that the
position of the optic cup/optic stalk boundary depends on Pax2 and Pax6
expression, hinting at a possible molecular interaction. Using gel shift
experiments, we confirmed the presence of Pax2- and Pax6-binding sites on the
retina enhancer of the Pax6 gene and on the Pax2 upstream control region,
respectively. Co-transfection experiments revealed a reciprocal inhibition of
Pax2 promoter/enhancer activity by Pax6 protein and vice versa. Based on our
findings, we propose a model for Pax gene regulation that establishes the proper
spatial regionalization of the mammalian visual system.
PMID- 11003834
TI - Positive and negative interactions of GDNF, NTN and ART in developing sensory
neuron subpopulations, and their collaboration with neurotrophins.
AB - Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN) and
neublastin/artemin (ART) are distant members of the transforming growth factor
beta family, and have been shown to elicit neurotrophic effects upon several
classes of peripheral and central neurons. Limited information from in vitro and
expression studies has also substantiated a role for GDNF family ligands in
mammalian somatosensory neuron development. Here, we show that although dorsal
root ganglion (DRG) sensory neurons express GDNF family receptors embryonically,
they do not survive in response to their ligands. The regulation of survival
emerges postnatally for all GDNF family ligands. GDNF and NTN support distinct
subpopulations that can be separated with respect to their expression of GDNF
family receptors, whereas ART supports neurons in populations that are also
responsive to GDNF or NTN. Sensory neurons that coexpress GDNF family receptors
are medium sized, whereas small-caliber nociceptive cells preferentially express
a single receptor. In contrast to brain-derived neurotrophic factor (BDNF)
dependent neurons, embryonic nerve growth factor (NGF)-dependent nociceptive
neurons switch dependency to GDNF, NTN and ART postnatally. Neurons that survive
in the presence of neurotrophin 3 (NT3) or neurotrophin 4 (NT4), including
proprioceptive afferents, Merkel end organs and D-hair afferents, are also
supported by GDNF family ligands neonatally, although at postnatal stages they
lose their dependency on GDNF and NTN. At late postnatal stages, ART prevents
survival elicited by GDNF and NTN. These data provide new insights on the roles
of GDNF family ligands in sensory neuron development.
PMID- 11003835
TI - A role for GATA5 in Xenopus endoderm specification.
AB - The endoderm gives rise to the gut and tissues that develop as outgrowths of the
gut tube, including the lungs, liver and pancreas. Here we show that GATA5, a
zinc-finger transcription factor, is expressed in the yolk-rich vegetal cells of
Xenopus embryos from the early gastrula stage onwards, when these cells become
committed to form endoderm. At mid-gastrula stages, GATA5 is restricted to the
sub-blastoporal endoderm and is the first molecular marker for this subset of
endodermal cells so far identified. We show that GATA4 and GATA5 are potent
inducers of endodermal marker genes in animal cap assays, while other GATA
factors induce these genes only weakly, if at all. When injected into the dorsal
marginal zone, GATA5 respecifies prospective mesoderm towards an endodermal fate,
thereby disrupting the convergence and extension movements normally undergone by
the dorsal mesoderm. The resulting phenotype is very similar to those seen after
injection of dominant negative versions of the FGF-receptor or the T-box
transcription factor, Xbra and can be rescued by eFGF. The ability of GATA5 to
respecify ectodermal and mesodermal cells towards endoderm suggests an important
role for GATA5 in the formation of this germlayer. In animal cap assays, GATA5 is
induced by concentrations of activin above those known to induce dorsal mesoderm
and heart, in an FGF-independent manner. These data indicate that the emerging
view for endodermal induction in general, namely that it is specified by high
levels of TGF-beta in the absence of FGF signalling, is specifically true for sub
blastoporal endoderm.
PMID- 11003836
TI - Genetic control of dorsal-ventral identity in the telencephalon: opposing roles
for Pax6 and Gsh2.
AB - We have examined the genetic mechanisms that regulate dorsal-ventral identity in
the embryonic mouse telencephalon and, in particular, the specification of
progenitors in the cerebral cortex and striatum. The respective roles of Pax6 and
Gsh2 in cortical and striatal development were studied in single and double loss
of-function mouse mutants. Gsh2 gene function was found to be essential to
maintain the molecular identity of early striatal progenitors and in its absence
the ventral telencephalic regulatory genes Mash1 and Dlx are lost from most of
the striatal germinal zone. In their place, the dorsal regulators, Pax6,
neurogenin 1 and neurogenin 2 are found ectopically. Conversely, Pax6 is required
to maintain the correct molecular identity of cortical progenitors. In its
absence, neurogenins are lost from the cortical germinal zone and Gsh2, Mash1 and
Dlx genes are found ectopically. These reciprocal alterations in cortical and
striatal progenitor specification lead to the abnormal development of the cortex
and striatum observed in Pax6 (small eye) and Gsh2 mutants, respectively. In
support of this, double homozygous mutants for Pax6 and Gsh2 exhibit significant
improvements in both cortical and striatal development compared with their
respective single mutants. Taken together, these results demonstrate that Pax6
and Gsh2 govern cortical and striatal development by regulating genetically
opposing programs that control the expression of each other as well as the
regionally expressed developmental regulators Mash1, the neurogenins and Dlx
genes in telencephalic progenitors.
PMID- 11003837
TI - Correlation of diversity of leg morphology in Gryllus bimaculatus (cricket) with
divergence in dpp expression pattern during leg development.
AB - Insects can be grouped into mainly two categories, holometabolous and
hemimetabolous, according to the extent of their morphological change during
metamorphosis. The three thoracic legs, for example, are known to develop through
two overtly different pathways: holometabolous insects make legs through their
imaginal discs, while hemimetabolous legs develop from their leg buds. Thus, how
the molecular mechanisms of leg development differ from each other is an
intriguing question. In the holometabolous long-germ insect, these mechanisms
have been extensively studied using Drosophila melanogaster. However, little is
known about the mechanism in the hemimetabolous insect. Thus, we studied leg
development of the hemimetabolous short-germ insect, Gryllus bimaculatus
(cricket), focusing on expression patterns of the three key signaling molecules,
hedgehog (hh), wingless (wg) and decapentaplegic (dpp), which are essential
during leg development in Drosophila. In Gryllus embryos, expression of hh is
restricted in the posterior half of each leg bud, while dpp and wg are expressed
in the dorsal and ventral sides of its anteroposterior (A/P) boundary,
respectively. Their expression patterns are essentially comparable with those of
the three genes in Drosophila leg imaginal discs, suggesting the existence of the
common mechanism for leg pattern formation. However, we found that expression
pattern of dpp was significantly divergent among Gryllus, Schistocerca
(grasshopper) and Drosophila embryos, while expression patterns of hh and wg are
conserved. Furthermore, the divergence was found between the pro/mesothoracic and
metathoracic Gryllus leg buds. These observations imply that the divergence in
the dpp expression pattern may correlate with diversity of leg morphology.
PMID- 11003838
TI - Developmental regulation of GDNF response and receptor expression in the enteric
nervous system.
AB - The development of the enteric nervous system is dependent upon the actions of
glial cell line-derived neurotrophic factor (GDNF) on neural crest-derived
precursor cells in the embryonic gut. GDNF treatment of cultured enteric
precursor cells leads to an increase in the number of neurons that develop and/or
survive. Here we demonstrate that, although GDNF promoted an increase in neuron
number at all embryonic ages examined, there was a developmental shift from a
mitogenic to a trophic response by the developing enteric neurons. The timing of
this shift corresponded to developmental changes in gut expression of GFR alpha
1, a co-receptor in the GDNF-Ret signaling complex. GFR alpha-1 was broadly
expressed in the gut at early developmental stages, at which times soluble GFR
alpha-1 was released into the medium by cultured gut cells. At later times, GFR
alpha-1 became restricted to neural crest-derived cells. GFR alpha-1 could
participate in GDNF signaling when expressed in cis on the surface of enteric
precursor cells, or as a soluble protein. The GDNF-mediated response was greater
when cell surface, compared with soluble, GFR alpha-1 was present, with the
maximal response seen the presence of both cis and trans forms of GFR alpha-1. In
addition to contributing to GDNF signaling, cell-surface GFR alpha-1 modulated
the specificity of interactions between GDNF and soluble GFR alphas. These
experiments demonstrate that complex, developmentally regulated, signaling
interactions contribute to the GDNF-dependent development of enteric neurons.
PMID- 11003839
TI - Gli2 functions in FGF signaling during antero-posterior patterning.
AB - Patterning along the anteroposterior (A-P) axis involves the interplay of
secreted and transcription factors that specify cell fates in the mesoderm and
neuroectoderm. While FGF and homeodomain proteins have been shown to play
different roles in posterior specification, the network coordinating their
effects remains elusive. Here we have analyzed the function of Gli zinc-finger
proteins in mesodermal A-P patterning. We find that Gli2 is sufficient to induce
ventroposterior development, functioning in the FGF-brachyury regulatory loop.
Gli2 directly induces brachyury, a gene required and sufficient for mesodermal
development, and Gli2 is in turn induced by FGF signaling. Moreover, the homeobox
gene Xhox3, a critical determinant of posterior development, is also directly
regulated by Gli2. Gli3, but not Gli1, has an activity similar to that of Gli2
and is expressed in ventroposterior mesoderm after Gli2. These findings uncover a
novel function of Gli proteins, previously only known to mediate hedgehog
signals, in the maintenance and patterning of the embryonic mesoderm. More
generally, our results suggest a molecular basis for an integration of FGF and
hedgehog inputs in Gli-expressing cells that respond to these signals.
PMID- 11003840
TI - Wingless and its signalling pathway have common and separable functions during
tracheal development.
AB - The Drosophila tracheal tree consists of a tubular network of epithelial branches
that constitutes the respiratory system. Groups of tracheal cells migrate towards
stereotyped directions while they acquire specific tracheal fates. This work
shows that the wingless/WNT signalling pathway is needed within the tracheal
cells for the formation of the dorsal trunk and for fusion of the branches. These
functions are achieved through the regulation of target genes, such as spalt in
the dorsal trunk and escargot in the fusion cells. The pathway also aids tracheal
invagination and helps guide the ganglionic branch. Moreover the wingless/WNT
pathway displays antagonistic interactions with the DPP (decapentaplegic)
pathway, which regulates branching along the dorsoventral axis. Remarkably, the
wingless gene itself, acting through its canonical pathway, seems not to be
absolutely required for all these tracheal functions. However, the artificial
overexpression of wingless in tracheal cells mimics the overexpression of a
constitutively activated armadillo protein. The results suggest that another gene
product, possibly a WNT, could help to trigger the wingless cascade in the
developing tracheae.
PMID- 11003842
TI - Control of tracheal tubulogenesis by Wingless signaling.
AB - The tubular epithelium of the Drosophila tracheal system forms a network with a
stereotyped pattern consisting of cells and branches with distinct identity. The
tracheal primordium undergoes primary branching induced by the FGF homolog
Branchless, differentiates cells with specialized functions such as fusion cells,
which perform target recognition and adhesion during branch fusion, and extends
branches toward specific targets. Specification of a unique identity for each
primary branch is essential for directed migration, as a defect in either the
EGFR or the Dpp pathway leads to a loss of branch identity and the misguidance of
tracheal cell migration. Here, we investigate the role of Wingless signaling in
the specification of cell and branch identity in the tracheal system. Wingless
and its intracellular signal transducer, Armadillo, have multiple functions,
including specifying the dorsal trunk through activation of Spalt expression and
inducing differentiation of fusion cells in all fusion branches. Moreover, we
show that Wingless signaling regulates Notch signaling by stimulating delta
expression at the tip of primary branches. These activities of Wingless signaling
together specify the shape of the dorsal trunk and other fusion branches.
PMID- 11003841
TI - MES-1, a protein required for unequal divisions of the germline in early C.
elegans embryos, resembles receptor tyrosine kinases and is localized to the
boundary between the germline and gut cells.
AB - During Caenorhabditis elegans embryogenesis the primordial germ cell, P(4), is
generated via a series of unequal divisions. These divisions produce germline
blastomeres (P(1), P(2), P(3), P(4)) that differ from their somatic sisters in
their size, fate and cytoplasmic content (e.g. germ granules). mes-1 mutant
embryos display the striking phenotype of transformation of P(4) into a muscle
precursor, like its somatic sister. A loss of polarity in P(2) and P(3) cell
specific events underlies the Mes-1 phenotype. In mes-1 embryos, P(2) and P(3)
undergo symmetric divisions and partition germ granules to both daughters. This
paper shows that mes-1 encodes a receptor tyrosine kinase-like protein, though it
lacks several residues conserved in all kinases and therefore is predicted not to
have kinase activity. Immunolocalization analysis shows that MES-1 is present in
four- to 24-cell embryos, where it is localized in a crescent at the junction
between the germline cell and its neighboring gut cell. This is the region of
P(2) and P(3) to which the spindle and P granules must move to ensure normal
division asymmetry and cytoplasmic partitioning. Indeed, during early stages of
mitosis in P(2) and P(3), one centrosome is positioned adjacent to the MES-1
crescent. Staining of isolated blastomeres demonstrated that MES-1 was present in
the membrane of the germline blastomeres, consistent with a cell-autonomous
function. Analysis of MES-1 distribution in various cell-fate and patterning
mutants suggests that its localization is not dependent on the correct fate of
either the germline or the gut blastomere but is dependent upon correct spatial
organization of the embryo. Our results suggest that MES-1 directly positions the
developing mitotic spindle and its associated P granules within P(2) and P(3), or
provides an orientation signal for P(2)- and P(3)-specific events.
PMID- 11003843
TI - The SPIRAL genes are required for directional control of cell elongation in
Aarabidopsis thaliana.
AB - Cells at the elongation zone expand longitudinally to form the straight central
axis of plant stems, hypocotyls and roots, and transverse cortical microtubule
arrays are generally recognized to be important for the anisotropic growth.
Recessive mutations in either of two Arabidopsis thaliana SPIRAL loci, SPR1 or
SPR2, reduce anisotropic growth of endodermal and cortical cells in roots and
etiolated hypocotyls, and induce right-handed helical growth in epidermal cell
files of these organs. spr2 mutants additionally show right-handed twisting in
petioles and petals. The spr1spr2 double mutant's phenotype is synergistic,
suggesting that SPR1 and SPR2 act on a similar process but in separate pathways
in controlling cell elongation. Interestingly, addition of a low dose of either
of the microtubule-interacting drugs propyzamide or taxol in the agar medium was
found to reduce anisotropic expansion of endodermal and cortical cells at the
root elongation zone of wild-type seedlings, resulting in left-handed helical
growth. In both spiral mutants, exogenous application of these drugs reverted the
direction of the epidermal helix, in a dose-dependent manner, from right-handed
to left-handed; propyzamide at 1 microM and taxol at 0.2-0.3 microM effectively
suppressed the cell elongation defects of spiral seedlings. The spr1 phenotype is
more pronounced at low temperatures and is nearly suppressed at high
temperatures. Cortical microtubules in elongating epidermal cells of spr1 roots
were arranged in left-handed helical arrays, whereas the highly isotropic
cortical cells of etiolated spr1 hypocotyls showed microtubule arrays with
irregular orientations. We propose that a microtubule-dependent process and
SPR1/SPR2 act antagonistically to control directional cell elongation by
preventing elongating cells from potential twisting. Our model may have implicit
bearing on the circumnutation mechanism.
PMID- 11003844
TI - Modular long-range regulation of Myf5 reveals unexpected heterogeneity between
skeletal muscles in the mouse embryo.
AB - The myogenic factor Myf5 plays a key role in muscle cell determination, in
response to signalling cascades that lead to the specification of muscle
progenitor cells. We have adopted a YAC transgenic approach to identify
regulatory sequences that direct the complex spatiotemporal expression of this
gene during myogenesis in the mouse embryo. Important regulatory regions with
distinct properties are distributed over 96 kb upstream of the Myf5 gene. The
proximal 23 kb region directs early expression in the branchial arches, epaxial
dermomyotome and in a central part of the myotome, the epaxial intercalated
domain. Robust expression at most sites in the embryo where skeletal muscle forms
depends on an enhancer-like sequence located between -58 and -48 kb from the Myf5
gene. This element is active in the epaxial and hypaxial myotome, in limb
muscles, in the hypoglossal chord and also at the sites of Myf5 transcription in
prosomeres p1 and p4 of the brain. However later expression of Myf5 depends on a
more distal region between -96 and -63 kb, which does not behave as an enhancer.
This element is necessary for expression in head muscles but strikingly only
plays a role in a subset of trunk muscles, notably the hypaxially derived ventral
body muscles and also those of the diaphragm and tongue. Transgene expression in
limb muscle masses is not affected by removal of the -96/-63 region. Epaxially
derived muscles and some hypaxial muscles, such as the intercostals and those of
the limb girdles, are also unaffected. This region therefore reveals unexpected
heterogeneity between muscle masses, which may be related to different facets of
myogenesis at these sites. Such regulatory heterogeneity may underlie the
observed restriction of myopathies to particular muscle subgroups.
PMID- 11003845
TI - Mab-3 is a direct tra-1 target gene regulating diverse aspects of C. elegans male
sexual development and behavior.
AB - Sex determination is controlled by global regulatory genes, such as tra-1 in
Caenorhabditis elegans, Sex lethal in Drosophila, or Sry in mammals. How these
genes coordinate sexual differentiation throughout the body is a key unanswered
question. tra-1 encodes a zinc finger transcription factor, TRA-1A, that
regulates, directly or indirectly, all genes required for sexual development. mab
3 (male abnormal 3), acts downstream of tra-1 and is known to be required for
sexual differentiation of at least two tissues. mab-3 directly regulates yolk
protein transcription in the intestine and specifies male sense organ
differentiation in the nervous system. It encodes a transcription factor related
to the products of the Drosophila sexual regulator doublesex (dsx), which also
regulates yolk protein transcription and male sense-organ differentiation. The
similarities between mab-3 and dsx led us to suggest that some aspects of sex
determination may be evolutionarily conserved. Here we find that mab-3 is also
required for expression of male-specific genes in sensory neurons of the head and
tail and for male interaction with hermaphrodites. These roles in male
development and behavior suggest further functional similarity to dsx. In male
sensory ray differentiation we find that MAB-3 acts synergistically with LIN-32,
a neurogenic bHLH transcription factor. Expression of LIN-32 is spatially
restricted by the combined action of the Hox gene mab-5 and the hairy homolog lin
22, while MAB-3 is expressed throughout the lateral hypodermis. Finally, we find
that mab-3 transcription is directly regulated in the intestine by TRA-1A,
providing a molecular link between the global regulatory pathway and terminal
sexual differentiation.
PMID- 11003846
TI - Lactational competence and involution of the mouse mammary gland require
plasminogen.
AB - Urokinase-type plasminogen activator expression is induced in the mouse mammary
gland during development and post-lactational involution. We now show that
primiparous plasminogen-deficient (Plg(-/-)) mice have seriously compromised
mammary gland development and involution. All mammary glands were underdeveloped
and one-quarter of the mice failed to lactate. Although the glands from lactating
Plg(-/-) mice were initially smaller, they failed to involute after weaning, and
in most cases they failed to support a second litter. Alveolar regression was
markedly reduced and a fibrotic stroma accumulated in Plg(-/-) mice.
Nevertheless, urokinase and matrix metalloproteinases (MMPs) were upregulated
normally in involuting glands of Plg(-/-) mice, and fibrin did not accumulate in
the glands. Heterozygous Plg(+/-) mice exhibited haploinsufficiency, with a
definite, but less severe mammary phenotype. These data demonstrate a critical,
dose-dependent requirement for Plg in lactational differentiation and mammary
gland remodeling during involution.
PMID- 11003847
TI - Developmental role of the SNF1-related kinase Hunk in pregnancy-induced changes
in the mammary gland.
AB - The steroid hormones 17 beta-estradiol and progesterone play a central role in
the pathogenesis of breast cancer and regulate key phases of mammary gland
development. This suggests that developmental regulatory molecules whose activity
is influenced by ovarian hormones may also contribute to mammary carcinogenesis.
In a screen designed to identify protein kinases expressed in the mammary gland,
we previously identified a novel SNF1-related serine/threonine kinase, Hunk
(hormonally upregulated Neu-associated kinase). During postnatal mammary
development, Hunk mRNA expression is restricted to a subset of mammary epithelial
cells and is temporally regulated with highest levels of expression occurring
during early pregnancy. In addition, treatment of mice with 17 beta-estradiol and
progesterone results in the rapid and synergistic upregulation of Hunk expression
in a subset of mammary epithelial cells, suggesting that the expression of this
kinase may be regulated by ovarian hormones. Consistent with the tightly
regulated pattern of Hunk expression during pregnancy, mammary glands from
transgenic mice engineered to misexpress Hunk in the mammary epithelium manifest
temporally distinct defects in epithelial proliferation and differentiation
during pregnancy, and fail to undergo normal lobuloalveolar development.
Together, these observations suggest that Hunk may contribute to changes in the
mammary gland that occur during pregnancy in response to ovarian hormones.
PMID- 11003848
TI - Attractive and repulsive interactions between female and male gametophytes in
Arabidopsis pollen tube guidance.
AB - Sexual reproduction in plants, unlike that of animals, requires the action of
multicellular haploid gametophytes. The male gametophyte (pollen tube) is guided
to a female gametophyte through diploid sporophytic cells in the pistil. While
interactions between the pollen tube and diploid cells have been described,
little is known about the intercellular recognition systems between the pollen
tube and the female gametophyte. In particular, the mechanisms that enable only
one pollen tube to interact with each female gametophyte, thereby preventing
polysperm, are not understood. We isolated female gametophyte mutants named
magatama (maa) from Arabidopsis thaliana by screening for siliques containing
half the normal number of mature seeds. In maa1 and maa3 mutants, in which the
development of the female gametophyte was delayed, pollen tube guidance was
affected. Pollen tubes were directed to mutant female gametophytes, but they lost
their way just before entering the micropyle and elongated in random directions.
Moreover, the mutant female gametophytes attracted two pollen tubes at a high
frequency. To explain the interaction between gametophytes, we propose a monogamy
model in which a female gametophyte emits two attractants and prevents
polyspermy. This prevention process by the female gametophyte could increase a
plant's inclusive fitness by facilitating the fertilization of sibling female
gametophytes. In addition, repulsion between pollen tubes might help prevent
polyspermy. The reproductive isolations observed in interspecific crosses in
Brassicaceae are also consistent with the monogamy model.
PMID- 11003849
TI - [Gratitude to the past and trust in the future] [In Process Citation]
PMID- 11003850
TI - [Omega and alpha, preserving and thriving] [In Process Citation]
PMID- 11003851
TI - [Treatment of benign vascular lesions with 585 nm pulsed dye laser].
PMID- 11003852
TI - [Laser treatment of cutaneous vascular lesions in childhood: prospective analysis
of our experience with 95 children].
AB - BACKGROUND: Recently the flashlamp-pumped dye laser has improved treatment of
cutaneous vascular lesions results since this laser acts much more vessel
specific than other laser (argon, Nd:Yag). The objective of this manuscript is to
analyze our experience in the treatment of vascular lesions in infancy with the
pulsed dye laser. MATERIAL AND METHODS: Ninety-five patients 18 years with
vascular lesions (85 nevus flammeus and 10 hemangiomas) were treated
prospectively with the flashlamp-pumped dye laser. The patients received therapy
until the lesion was almost clear, or until the lesion failed to respond. All
patients were examined during the course of their treatment to assess the
clinical evolution and the incidence of adverse effects associated with the use
of the laser. RESULTS: The study consisted of 54 females and 41 males ranged in
age from 3 months to 18 years, with the average age being 7.3+/-5.2 years. Only
six children were treated with less than six months of age. Seventy-eight
vascular lesions were located on the face, nine on the neck, eight on the
extremities, five on the trunk, and two on other regions (perineal area and
scalp). The number of treatment sessions needed for the resolution of the
cutaneous vascular lesion (in 52 nevus flammeus and 10 hemangiomas, at the
moment) was 9.8+/-7.5 (range 1 to 36), with variations in relation to the type of
vascular lesion (more sessions in nevus flammeus than hemangiomas) and their
anatomical location (more sessions in the face and less in shoulder, arms and
lips). The adverse effects were slights and transitories. CONCLUSIONS: Laser
therapy is useful and safe in the treatment of cutaneous vascular lesions in
infancy. Major determinants of treatment response are type of cutaneous vascular
lesion and location, and also size and patient's age.
PMID- 11003853
TI - [Clinical and radiological characteristics of primary pulmonary tuberculosis in
adolescents].
AB - OBJECTIVE: The aim of this study was to investigate the incidence, clinical and
radiological particularities of primary pulmonary tuberculosis in children
between 10 to 16 year-old in our community. PATIENTS AND METHODS: The medical
records and chest X-ray of all children under 16 years old diagnosed of primary
pulmonary tuberculosis between 1982 to 1996, and a similar characteristics
control group diagnosed of bacterial pneumonia were reviewed. The difference
between teenager with tuberculosis and pneumonia and between patients with
tuberculosis under 10 years and order were analysed. RESULTS: Between January
1982 and December 1996, 83 children with age range from 10 to 16 years were
diagnosed of primary pulmonary tuberculosis. The incidence has been 15,5
cases/100000 h < 16 years/year. The primary pulmonary tuberculosis whole
incidence in children under 16 year-old has been 17 cases/100000 h/year (182
cases). The adolescents fits to 40.5% of the hold group. 51.2% were girls and
49.8% were boys. Middle age has been 14.2+/-0.18 years with a progressive
increased with the age. Anorexia (38% vs. 16.6%) and asthenia (38% vs 19.4%) have
been more frequents in teenagers with tuberculosis. Cough has been the most
frequent symptom in both groups (61.9% and 77.7%), and respiratory distress has
been the most characteristic of tuberculosis (17.8% vs 2.7%). Thoracic pain was
more frequent in patients with tuberculosis 10 years or older (57.8% and 7.8%).
Laboratory values are not specific. Pleural effusion (46.4% vs 22.2%) and
mediastinal lymphadenophaty (60.1% vs. 40.4%) were the most characteristic X-ray
finding in teenagers and children under 10 years with primary pulmonary
tuberculosis respectively. CONCLUSIONS: Primary pulmonary tuberculosis has a high
incidence in the teenager population in our community with a progressive
increased with the age. The clinical and laboratory values are unspecific in this
age group. The most characteristic X-ray finding is pleural effusion (46.4% of
the patients).
PMID- 11003854
TI - [Treatment of suprastomal tracheomalacia by anterior cricoid suspension].
AB - BACKGROUND: One of the reasons of failure to decannulate patients after airway
surgery or long-term tracheostomy is suprastomal tracheomalacia. OBJECTIVES:
Evaluate the results obtained in the treatment of suprastomal tracheomalacia by
anterior cricoid suspension. MATERIAL AND METHODS: We present 8 patients with
suprastomal tracheomalacia associated to long-term tracheostomy corrected by this
technique. Prior to surgery, other causes of airway obstruction, as well as the
presence of gastroesophageal reflux disease should be ruled out. Results 5
females and 3 males wer treated by this technique. Mean age at surgery was 4,1 +/
0,97 years (range, 1,5-8,8 years). anteroposterior suprastomal collapse occluding
75% of the trachea was observed in 5 cases, and 75-90% in other three. All the
patients were extubated successfully, although in one case stridor recurred
because of residual suprastomal malacia that required a new surgical procedure.
After a follow-up of 38,7+/-7,39 months (range, 1 month-4,6 years), the patients
are decannulated and going well. Conclusions It is an safe surgical technique,
easily reproducible and with low costs.
PMID- 11003855
TI - [Technetium-99m-dimercaptosuccinic acid (DMSA) scintigraphy in the first febrile
urinary tract infection in children].
AB - OBJECTIVE: The objective of this study was to evaluate the findings of 99mTc-DMSA
renal scintigraphy in children with their first acute febrile urinary tract
infection in relation with several clinical-biological parameters and other
imaging studies and a long-term follow up. MATERIAL AND METHODS: 103 children
between 1 month and 10 years old with their first acute febrile urinary tract
infection were studied by means of clinical and laboratory assessment, renal
ultrasonography and 99mTc DMSA renal scintigraphy in the acute illness period.
Patients were divided into two groups, those under 2 years old (n = 63) and those
over 2 years old (n = 40). RESULTS: Cortical scintigraphy showed renal changes in
56 patients (54,5%). Children over 2 years of age had a higher incidence of renal
lesions than younger children (39,7% vs. 77,5%). Ultrasonography measuring renal
volume showed a simple concordance with scintigraphy in 64% of the patients.
Reflux was demonstrated in 23 patients (22,3%) without differences between
patients with normal or abnormal cortical scintigraphy. After having studied the
factors that were associated independently to the pathological results in the
scintigraphy through a logistical multivariant regression, it was observed that
the child's age, the elevation of the PCR and the alterations of the renal volume
were significant according to statistics and also associated to a larger amount
of pathological DMSA scintigraphy. CONCLUSIONS: DMSA scintigraphy associated with
other diagnostic methods can improve the sensitivity and specificity to establish
renal damage stage. During the follow-up the acute lesions disappeared or
improved in all cases and the chronic lesions have not been modificated.
PMID- 11003856
TI - [Suicide in pediatric patients: 30 cases].
AB - OBJECTIVE: The aim of this study was to evaluate suicide attempts in pediatric
population and analyze the morbimortality. PATIENTS AND METHODS: We have reviewed
thirty reports from twenty six patients hospitalized in UCIP by suicide attempts
with an average age of 15.5 years (range 11-19) between January 1991 and April
1999. Results The following variables were analyzed: age, sex, precipitating
suicidal event, number of suicide attempts, symptoms, method, treatment and
mortality. The age group with more incidence was between 14 and 17 years with 73%
(22 cases). The majority were girls (96%). There were prior suicide attempt in
40% (12 cases). Psychiatric disorder more frequently associated was anorexia
nervosa in 70%. The most common method was self-poisoning (93%). Neurologic
symptoms were seen in 20 cases. The more used treatment was activated coal. The
clinical outcome was favourable and only two patients died. Conclusions The
suicide attempts are happening more frequently in the adolescence in the last
years. Pediatricians have to be prepared to recognize and provide prompt
attention to acute medical, familiar and social problems.
PMID- 11003857
TI - [Cardiac rhabdomyomas in tuberous sclerosis: clinical symptoms and course in 18
cases diagnosed in childhood].
AB - OBJECTIVE: Tuberous sclerosis is a neurocutaneous syndrome with autosomal
dominant inheritance. The reported incidence is 1:10000. Recent echocardiographic
studies showed a 50% to 64% incidence of cardiac rhabdomyomas in patients with
tuberous sclerosis. The objective is to assess the history of cardiac
rhabdomyomas in infants and children with tuberous sclerosis. METHODS: From 1970
to 1998, 39 patients were diagnosticated of tuberous sclerosis. Cardiac
rhabdomyomas were present in 18 of them, 9 girls and 9 boys. Ecocardiografic
follow up ranged from 1 month to 14 years. RESULTS: Echocardiographic studies
showed rhabdomyomas located in the interventricular septum, ventricles, right and
left atrium. A newborn, had subaortic obstruction related to a tumor who precised
surgery excision. Standard electrocardiogram showed different disturbances:
premature auricular and ventricular contractions, conduccion disturbances and pre
excitation syndromes. Two patients, both neonates, had severe arrhythmias, one of
them debuted with supraventricular tachycardia due to an accessory hidden left
atrio-ventricular pathway who undergone successful radiofrequency ablation; and
the other patient was diagnosticated prenatally of fetal complete heart block and
precised permanent pacemaker at birth. After a follow up of 5.1+/-4.5 years,
spontaneous regression of the tumors was shown in 12 of the 18 patients with
complete resolution in two of them. All of them are asymptomatic nowadays.
CONCLUSIONS: Our findings confirms that cardiac rhabdomyomas are most often a
benign condition in which spontaneous regression is the rule and surgery is only
recommended for patients with life threatening obstruction or refractory
disrhythmias in the neonatal period when the tumor size is maximum.
PMID- 11003858
TI - [Evaluation of a home care program for children with cancer].
AB - The home care team dependent from the pediatric oncology unit in our institution
started working in April, 1997. We evaluate in this paper the medical activities
accomplished in seventeen month experience. The team is constituted by a
pediatric oncologist, two pediatric nurses and a clinical assistant with
experience in the specialty. The geographic area we cover is la Communidad
Valenciana. We directly attend children living in Valencia city and its
metropolitan area. For the rest of patients, we coordinate the interventions of
the local primary care teams and local hospitals. 127 patients have been admitted
in the home care unit in 433 occasions. The immediate reasons for the admission
were: early discharge from the hospital (61%), followed by the administration of
antibiotics (18%) and chemotherapy (12%) at home. We attended 17 children in the
terminal phase of their diseases. Five of them required opioid treatment for pain
control. Six out of eight patients living in the area of direct intervention of
the home care team died at home. The most common cause of discharge (73%) was the
achievement of the goals planned when the patient was included in the program.
Only in two cases (0.5%) we did not found enough cooperation from the parents and
the treatment was completed in the hospital. This program has been well accepted
by our patients and their parents and permits to shorten the stay in the
hospital.
PMID- 11003859
TI - [Multiple type I pseudohypoaldosteronism: neonatal management and outcome].
AB - Multiple type I pseudohypoaldosteronism (PHA-I) is an autosomal recessive
condition with multiple target-organ unresponsiveness to aldosterone, manifested
early after birth with severe salt-wasting and hyperkalemia. Case 1. Female
infant born at term after an uneventful pregnancy. One female sibling died in the
first week of life with hyperkalemia. The diagnosis of multiple PHA-I resulted
from a picture of dehydratation, hyperkalemia and hyponatremia with increased
plasma renin activity (PRA), plasma aldosterone and sweat electrolytes. The
treatment consisted of salt and sodium bicarbonate supplements, restricted
potassium intake, cation exchange resins and high fluid intake. During first year
she was hospitalized for severe salt-losing crises. At 7 years of age, she needs
salt and sodium bicarbonate supplements and cation exchange resins. She has a
normal growth and neurodevelopment. Case 2. Seven-day female newborn with
consanguinity in maternal family. Pregnancy and delivery were uncomplicated. On
admission she was severely dehydrated with hyponatremia, hyperkalemia, metabolic
acidosis and elevated PRA, plasma aldosterone and sweat electrolytes. She
remained hospitalized for six months and she was dependent on high amounts of
salt and sodium bicarbonate supplements, fluid intake and cation exchange resins.
Growth and neurodevelopment are normal. CONCLUSIONS: Multiple PHA-I may be
suspected in a newborn with salt-loss and hyperkalemia without glucocorticoid
defect. The frequent episodes of dehydratation during the first year of life
require long hospitalization. The improvement with age make possible an
ambulatory control after the first year of life.
PMID- 11003860
TI - [Neonatal cerebral thrombosis and deficit of factor V leiden].
AB - Background Cerebral venous thrombosis is an inusual disease in neonatal age.
Increasing reports of this disorder had described since magnetic resonance
angiography is used. Case report Newborn of apropriate seze for gestational age
was delivered at 35 weeks of gestation. Refered a severe hipoxic-isquemic disease
with multisistemic afectation. The second day of life presented disseminated
intravascular coagulation with pulmonary bleeding. The third day, the infant
developed seizures that required treatment with diazepam in continuous
perfussion. MR angiography visualized superior sagital and transvers sinus
thrombosis. Coagulation study detected factor V Leiden. Comments Frecuently
venous cerebral thrombosis is presenting with lethargy and seizures. The most
common vessels involved are sagital and transvers sinus. It is described in
association with exogenous risk factors that increasing blood hyperviscosity and
additional inhered coagulation dissorders such as defects on antihrombina III,
protein C and S and activate protein C resistance. The last defect has a hight
prevalence in subjects with trombosis events.
PMID- 11003861
TI - [Adult respiratory distress in hemolytic-uremic syndrome secondary to
pneumococcal meningitis].
PMID- 11003862
TI - [Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis: report
of three cases].
PMID- 11003863
TI - [Idiopathic arterial calcification in children: post-mortem diagnostic of a
premature newborn].
PMID- 11003864
TI - [Acute parotitis caused by Epstein-Barr virus].
PMID- 11003865
TI - [Radiographic changes in cortical bone].
PMID- 11003866
TI - [Successful breast-feeding].
PMID- 11003867
TI - [Myocarditis caused by respiratory syncytial virus].
PMID- 11003868
TI - [Immunoglobulins to prevent varicella infection].
PMID- 11003869
TI - [Phytophotodermatitis].
PMID- 11003870
TI - [Rural gypsy population and breast-feeding. Is it an atypical population?].
PMID- 11003871
TI - [Streptococcus pyogenes invasive infection].
PMID- 11003873
TI - [II spanish congress on pediatric reumatology] [In Process Citation]
PMID- 11003872
TI - [Eating disorders and their etiology. Not only fashion and media].
PMID- 11003874
TI - [Information] [In Process Citation]
PMID- 11003875
TI - [Is smoking a pediatric epidemic?].
PMID- 11003876
TI - [Hormonal reference values for adrenocortical function in healthy children from
Zaragoza].
AB - OBJECTIVE: Estimation of reference values for basal serum concentrations of
adrenocorticotropic hormone (ACTH), cortisol, 11-deoxycortisol, 17-OH
progesterone (17-OHP), plasma renin activity (PRA), aldosterone, -4
androstendione ( 4A) and dehydroepiandrosterone sulphate (DHA-S) in healthy
children from Zaragoza. METHODS: Reference population were healthy children aged
0 to 14, with normal weight and height, living in the metropolitan area of
Zaragoza (Spain). It is a transversal study. Reference values and ranges for
ACTH, cortisol, 11-deoxycortisol, 17-OHP, PRA, aldosterone, 4A and DHA-S were
estimated, and changes in concentrations were analyzed in relation to age, sex
and puberal stage. RESULTS: Reference values have been classified by puberal
stage and age in eleven groups for every sex: Tanner I (umbilical cordon, 3 days,
4-30 days, 1-6 months, 6 months-4 years, 4-7 years, 7-10 years, 10-14 years),
Tanner II, Tanner III and Tanner IV-V. Sex did not influence ACTH, cortisol, 17
OHP and PRA concentrations, and there are punctual differences in 11
deoxycortisol, aldosterone, 4A and DHA-S levels. 17-OHP, 11-deoxycortisol and
aldosterone concentrations significantly decreased from birth to 6 months-4 years
and subsequently kept steady. The maximal concentration of ACTH, and ARP in blood
cord significantly decreased until the period 6 months-4 years, and subsequent
differences among different age groups, and between prepuberal and puberal groups
are scarce. The highest concentration of 4A and DHA-S were observed in blood cord
and third day of life, decreased until the lowest level in 6 months-4 years and
progressively increased with age in prepuberty, and between prepuberty and
puberty. The lowest concentration of cortisol was detected in 4-30 days,
increased until 6 months-4 years and kept steady along the prepuberty and
puberty. CONCLUSION: It is necessary that every population establish own
reference values for ACTH, cortisol, 11-deoxycortisol, 17-OHP, PRA, aldosterone,
4A and DHA-S during infancy, childhood and adolescence, according to age, sex and
puberal stage.
PMID- 11003877
TI - [Secular trends of body adipose tissue in prepubertal children].
AB - OBJECTIVE: To determine whether there is a significant difference between
anthropometric measurements of prepubertal children and the measurements of
another sample with similar characteristics, studied fifteen years ago. MATERIAL
AND METHODS: We studied 859 children, 453 males and 406 females, from the age of
5.0 to 10.0 years. Weight, height, arm circumference and skinfold thicknesses in
the biceps, triceps, subscapular and suprailiac were determined. Body mass index,
body density, total fat and percentage fat were calculated and their values
compared with those obtained 15 years ago in 1,617 children with similar
characteristics. Difference between means were calculated with Student's single
sample t-test. RESULTS: Weight increased in all the ages, with significant
differences in males at 7, 8 and 9 years (p<0.001) and in females after the age
of 6 years (p< 0.05). Height significantly increased at all ages and in both
sexes, except in females at the age of 5 years. Body mass index increased only at
the ages of 8 and 9 years in males (p<0.01). Skinfold thicknesses significantly
increased in both sexes and at all ages (p<0.05). Body density decreased (p<0.01)
and body fat increased, both in kilograms and in percentage (p<0.01).
CONCLUSIONS: During the 15 years studied, height and weight increased
significantly. Body mass index did not increase significantly, whereas body fat
(skinfold thicknesses and fat compartment) significantly increased.
PMID- 11003878
TI - [Bone maturity evaluation by automatized metric measurements].
AB - OBJECTIVES: Precision and rapidity of computerised procedures facilitate bone
maturity evaluation by measuring bone images. In this paper we analysed the
adequacy of several of these measures to evaluate growth or bone maturity.
MATERIAL AND METHODS: To determine growth or maturity indicating parameters, two
hundred X-rays of the left hands and wrists of 2 to 18 years old children were
examined by an automated image analysis procedure (IMAGO-2). Children were
examined every six months (18 to 36 months) obtaining several auxological data
(weight, height, bone maturity, TW2 methods, etc.). The relationship between the
automated indicating parameters of maturity or growth and the auxological data
were studied (linear correlation and multiple regression). RESULTS: All
parameters correlate with the chronological age. The area parameter presents the
highest coefficient of correlation with weight and Speed of Growth. The perimeter
presents the best correlation with Height and bone maturity (TW2). Variations in
some separation measurements from the circular ones relate well with auxological
data changes. CONCLUSIONS: It is difficult to categorically catalogue one
measurement as the only and exclusive indicator of maturity or growth. The
studied parameters correlate best with bone maturity (TW2) when compared with
those of the auxological data (weight, height) which could indicate their
usefulness to evaluate bone maturity.
PMID- 11003879
TI - [Opinion of heads of schools about the impact of school setting factors on the
attitude of children and youngsters regarding smoking].
AB - AIM: Knowing the influence of school environment on children and teenagers'
attitudes about tobacco consumption. METHODS: A survey was carried on 3.050
Spanish school headmasters (16% of the total in Spain), who were asked about the
main variables related to the school environment able to influence the attitude
of children and teenagers towards tobacco, such as the fulfilment of the official
anti-tobacco legislation at educational centres, the education for nicotine
poisoning prevention, or the teachers attitudes about tobacco, among others.
Multiple regressions were made so as to value the variables that most influence
the pupils' tasting tobacco and becoming usual smokers. RESULTS: In the opinion
of the headmasters the variables that individually most influence the percentage
of pupils that have tasted tobacco are the percentage of smoker teachers (beta
0.21) and the percentage of teachers who smoke in the presence of pupils (beta
0.091), as on the percentage of students usual smokers (beta 0.21 and 0.19
respectively). All the variables from school environment analysed jointly,
explain some percentages of variance of the 9.65% and 10.7% of the estimated
percentages of pupils who have tasted tobacco and pupils that are usual smokers,
respectively. CONCLUSIONS: The efforts most be doubled, in order to reach the
real fulfilment of the official anti-tobacco legislation in all educational
centres and the pupils receive teachings for the prevention of tabaquisme in the
context of Health Education, since these measures may make the schools play a
more determinant role in the prevention of the nicotinism.
PMID- 11003880
TI - [Clinical manifestations and biological markers in the natural history of HIV-1
infection in vertically infected children. Longitudinal study].
AB - OBJECTIVE: To study the relationship among clinical symptoms and biological
markers as predictive value of progression to death in HIV-1 vertically infected
infants. PATIENT AND METHODS: We carry out a prospective study in 43 HIV-1
infants with a mean age of 4.27 (range: 0-11.8 months). None of the infants'
mothers had received any antiviral treatment during pregnancy. None of the
infants were breastfed. They were routinely assessed for clinical symptoms during
follow-up. RESULTS: Cox regression analysis was used to study the hazard ratio
(HR) of progression to death. For the median viral load > 5 log10, the HR was
6.42 (95% CI, 1.28-32.03) (p = 0.023) and 6.84 (95% CI, 1.52-30,69) (p = 0.012)
for biological phenotype of viral isolates with rapid replication and high titter
(R/H-X4). We also study the predictive value of the clinical symptoms and we
observe that the symptoms with more HR of progression to death were the
progressive encephalopathy (3.60 [95% CI, 0.92-14.06; p = 0.065]) and the
cardiopathy (6.29 [95% CI, 1.59-24.85; p = 0.008]). CONCLUSIONS: Our data
indicate that viral load > 5 log10 and biological phenotype R/H-X4 of virus
isolates along the study are predictive markers of progression to death. In
addition, the progressive encephalopathy and cardiopathy were also markers of
progression death.
PMID- 11003881
TI - [Antibiotic prescribing patterns for pediatric inpatients with acute respiratory
tract infection].
AB - BACKGROUND: Children with acute respiratory tract infection (ARTI) represent an
important target group for efforts aimed at reducing unnecessary antibiotic use.
OBJECTIVE: To present the epidemiological data and evaluate the effect of
clinical, laboratory, radiological and microbiological data on the decision to
prescribe antibiotics to pediatric patients with ARTI as well as to seek criteria
that would justify antibiotic use. PATIENTS AND METHODS: A retrospective review
was made of the clinical histories of 147 previously healthy children,
consecutively admitted to our hospital with ARTI for 1 year (May 1996-April
1997). Patients were divided in two groups: those not treated with antibiotics (n
= 92) and those treated (n = 55). Data from the two groups were compared with a
statistical computer program (R-Sigma). RESULTS: Of the 147 patients studied,
mean age was 2.5 years (range 0-14 years) and 85 (58%) males. One-hundred-and
five patients (72%) had previously been attended to in the emergency room, and 45
patients (30%) had been treated with antibiotics. Upper respiratory tract
infection was diagnosed in 81 patients (54%), bronchitis in 28 (18%),
bronchiolitis in 23 (15%) and pneumonia in 15 (10%). Ninety-seven patients (66%)
had viral infection and only two (1%) had bacterial infection. Syncytial
respiratory virus was isolated in 41 patients (28%) and adenovirus in 30 (20%).
In the untreated group, the longer duration of symptoms before admission,
lymphocytosis, clinical diagnosis of bronchiolitis and normal thorax X-ray, were
statistically significant. In the treated group, fever, leukocytosis,
neutrophilia and a diagnosis of pneumonia were statistically significant. Length
of stay was longer in this group than in the untreated group. CONCLUSIONS: It is
difficult to prescribe antibiotics on the basis of bacteriologic data.
Laboratory, analytic and radiological data can be helpful in the rational use of
antibiotics.
PMID- 11003882
TI - [Antibiotic prescribing patterns in primary health care. Do pediatricians use
antibiotics rationally?].
AB - OBJECTIVES: To determine antibiotic prescribing patterns in the pediatric
(infants and children) population attended to at a primary health care centre in
the community of Madrid. We also wanted to determine the necessity or otherwise
of antibiotic therapy and whether the selected antibiotic drug was appropriate
for the pathology diagnosed. METHODS: Retrospective study of all infectious or
respiratory processes diagnosed during 1 year and of the respective antibiotic
cycles prescribed in all patients under the age of 4 years. The prescribing
physician and the appropriateness of all therapeutic decisions, including those
where the decision was not to treat with antibiotic drugs, were analyzed.
RESULTS: We evaluated 910 children under the age of 4 years with a total of 3,
847 processes (mean of 4.55 +/-3.6 processes per child per year). Sixty-three
percent of the children received at least one cycle of antibiotic drugs per year
(mean 1.63+/-1.69 cycles of treatment per child per year). Of all therapeutic
decisions, 85.2% were considered appropriate. In 36% of the processes antibiotics
were prescribed (1,386 cycles), 46% of which were considered inappropriate either
because no antibiotic therapy should have been given (71.6%) or because the
chosen drug was not appropriate for the pathology (28.4%). There were significant
differences among the evaluated physicians. The most correct decisions were taken
by the pediatrician in the outpatient clinic, especially when compared with
physicians in the emergency ward (p<0.0001). The most frequently prescribed
antibiotic drugs were amoxicillin (41.2%) and amoxicillin combined with
clavulanic acid (33%). Cephalosporin accounted only for 6.9% of the
prescriptions. CONCLUSIONS: Antibiotic therapy is overprescribed in children, a
situation that should be corrected.
PMID- 11003883
TI - [Partial seizures in a newborn with tuberous sclerosis].
AB - Tuberous sclerosis is characterized by the potential for hamartomatous growth in
multiple organs. Common manifestations are hypomelanotic spots, facial
angiofibromas, subependymal hamartomas, cortical tubers, cardiac rhabdomyomas,
retinal hamartomas, and so on. Seizures and mental retardation are frequent. It
is an autosomal dominant disease but there is a high percentage of spontaneous
mutations. Neonatal diagnosis is exceptional. We report a case of a female term
newborn who presented partial motor seizures at the third day of life. Physical
examination revealed only a disturbance of cardiac rhythm. Echocardiography
showed ventricular intramural rhabdomyomas. Magnetic resonance imaging disclosed
periventricular subependymal nodules and cortical tubers. A retinal hamartoma was
found in the right eye. At the age of 1 month, hypomelanotic spots were evident
on the back skin. The patient had infantile spasms, followed by poorly controlled
partial complex seizures together with severe psychomotor retardation.
Examination of both parents was normal. We discuss the uncommon diagnosis of
tuberous sclerosis during the neonatal period, as well as the exceptional mode of
presentation of our patient, with seizures in the early neonatal period, a
phenomenon rarely reported in the literature.
PMID- 11003884
TI - [Partial trisomy 1q due to maternal translocation].
PMID- 11003885
TI - [Neonatal hyperthyroidism].
PMID- 11003886
TI - [Chilaiditi's syndrome].
PMID- 11003887
TI - [Thanatophoric dwarfism in twin pregnancy].
PMID- 11003888
TI - [Bilateral coxalgia in a girl with Down syndrome].
PMID- 11003889
TI - [Detection of abnormalities in carbohydrate metabolism in cystic fibrosis].
PMID- 11003890
TI - [Detection of abnormalities in carbohydrate metabolism in cystic fibrosis] [In
Process Citation]
PMID- 11003891
TI - [Non-invasive mechanical ventilation for congenital central alveolar
hypoventilation].
PMID- 11003892
TI - [Endopleural urokinase: adverse reaction].
PMID- 11003893
TI - [Remission of nocturnal enuresis in three patients with orthodontic advance
mandibular appliance].
PMID- 11003894
TI - [Use of albumin in the critically ill and evidence-based medicine].
PMID- 11003895
TI - [Pneumococcal vaccines. One solution to several problems?].
PMID- 11003896
TI - [Rational use of antibiotics in pediatrics: impact of a rapid test for detection
of beta-haemolytic group A streptococci in acute pharyngotonsillitis].
AB - OBJECTIVES: To assess the reliability and validity of a rapid test for the
identification of Streptococcus pyogenes in the pharyngeal exudate of children
presenting with pharyngotonsillitis. To evaluate the impact of its use in
outpatient clinics on antibiotic use, on the incidence of second medical visits
and complications, and on the degree of parental satisfaction. PATIENTS AND
METHODS: After a clinical diagnosis of acute pharyngitis was established and
written informed consent obtained from the parents, dual throat swabs were
collected from 430 children who attended the emergency department of our hospital
or the pediatric offices of three health centers in our area. The first specimen
was examined by the rapid test, QuickVue Flex Strep A, and the second one was
sent to the laboratory for conventional culture. As a rule, antibiotics were
indicated only when the rapid test was positive. Special emphasis was placed on
explaining to parents that treatment was not necessary when the test was
negative. Telephone follow-up was provided to the family during the next four
weeks, after which a satisfaction survey was carried out. RESULTS: The
sensitivity of the investigated rapid test was 91.2% (negative predictive value:
96.5%) and specificity was 96.2% (positive predictive value: 90.4%). Antibiotics
were given to 41.9% of the patients, approximately half the expected rate in the
absence of the rapid test. There was no significant difference in the number of
second visits or hospitalizations between the groups of treated and non-treated
subjects. Clinical evolution was good in all cases. The degree of parental
satisfaction was very high, independent of the treatment given to the patients.
CONCLUSIONS: The rapid test for the detection of group A streptococci is a
reliable tool for the selection of patients able to benefit from antibiotic
treatment. It is easy to handle and apply and its use allows a significant
reduction in the administration of antibiotics in pharyngotonsillitis. Most users
accept and are satisfied with this novel diagnostic and therapeutic procedure.
PMID- 11003897
TI - [Immunogenicity of the 23-valent pneumococcal vaccine in children with chronic
renal disease].
AB - OBJECTIVE: To study the immunogenicity of the 23-valent pneumoccal vaccine in
children with chronic renal disease and in those with nephrotic syndrome, and to
compare it with the response in healthy children. METHODS: The vaccine was
administered to 150 children aged 2-18 years: 113 with renal diseases (26 with
nephrotic syndrome, 23 with severe grades of vesicoureteral reflux, 16 with
chronic renal insufficiency, 6 renal transplant recipients, 6 requiring dialysis
and 36 with other renal diseases) (group 1) and 37 healthy (group 2). Specific
IgG antibodies concentrations were measured by ELISA before and 30 days after
vaccination. The results obtained in both groups were compared. We compared too
the response observed between the subgroup of children with renal diseases in
which pneumococcal vaccine is indicated (nephrotic syndrome, chronic renal
insufficiency, renal transplant and those requiring dialysis (group 3) and
healthy children. RESULTS: 87.3% of children showed a 2-fold increase in antibody
concentrations after vaccination. No significant differences were observed
between the three groups. We considered that the vaccine was immunogenic in 78.4%
of healthy children, in 77.9% of group 1 children and in 72.5% of those in the
group 3 (p = 0,533). A lower response was observed in children with a kidney
transplant and in those requiring dialysis. CONCLUSIONS: These results suggest
that 23-valent pneumococcal vaccine is immunogenic in children with chronic renal
diseases or nephrotic syndrome and may protect these patients from invasive
pneumococcal disease. The importance of improved vaccine coverage is emphasized.
PMID- 11003898
TI - [Hospital guidelines on breastfeeding in the north-center of Spain].
AB - OBJECTIVES: To investigate the influence of the maternity protocols on frequency
and prevalence of breastfeeding in the 15 most important maternity units from the
north-center region of Spain. METHODS: From October 1992 to December 1992 we
collected 1175 newborn babies and we followed them up for 12 months. A protocol
study was designed to collect the data in DBase IV format and the statistical
study was done with SPSS version Window 6.0. chi 2 test was applied. RESULTS: The
presence of the father at the delivery did not influence breastfeeding. The
rooming-in was an adverse factor. Instrumental delivery and specially cesarean
section act as an adverse factor for breastfeeding. To feed the baby with glucose
or water and to delay the breast exposure was also negative to breastfeeding.
CONCLUSIONS: The protocols used in the Spanish north-center maternity units are
at a distance from those of Baby-friendly-Hospital Initiative. The early exposure
to the breast and the restriction of bottle-feed with glucose in the early hours
of life favours breast feeding. Instrumental delivery act as an adverse factor
for breastfeeding.
PMID- 11003899
TI - [Tuberculous meningitis: a disease in regression in our country?].
AB - OBJECTIVE: Our aim was to analyse clinical, diagnostic, therapeutical and
evolutionary features in a pediatric population with tuberculous meningitis.
PATIENTS AND METHODS: The medical records of thirteen children with this
diagnosis admitted to Hospital Infantil Virgen del Rocio from Seville (Spain)
between 1984 and 1999 were reviewed. RESULTS: The mean age was 2,35 +/- 2,3
years. The symptoms upon admission were: fever in 11 children, anorexia and
vomiting in 8, disturbance of the consciousness in 7. Meningeal signs in 6, all
of them older than 20 months, the remaining seven showed irritability and four of
these ones hypertense fontanelles. Three patients were in the first stage of the
disease, 9 in the second and 1 in the third, according to the Medical Research
Council. CSF findings were indicative in all the cases. Five children had
bacilloscopy positive and Mycobacterium tuberculosis was isolated in 6 patients,
sometimes in CSF others in gastric juice. Mantoux skin test was positive in 11.
Radiographic studies demonstrated abnormal chest findings in 8 patients (hiliar
adenopathy, 1; miliary pattern, 2; and infiltrates, 5). Pathology cranial
computed tomography showed in all the cases and the electroencephalogram was
slowed down in the initial phases in 11. Two children died and the neurological
complications were the most frequent, appearing in 9 patients. Without
consequences cured 4 patients, the rest presented cognitive, visual and motor
deficits, sensibility skin disturbance and late seizures. No case has been
observed during the last 5 years. CONCLUSIONS: Fast diagnosis tests used for M.
tuberculosis identification were useful to begin an antituberculous treatment in
a high suspicion of meningeal affectation by this German patient. The early
treatment will decrease complications and consequences by this disease. A
decrease in the incidence looks to be in spite of the VIH infection increase
nowadays.
PMID- 11003900
TI - [Ureaplasma urealyticum and pertussis-like syndrome].
AB - BACKGROUND: Ureaplasma urealyticum is associated with respiratory pathology in
the neonates and preterm neonates. However, this association has been poorly
studied in infants and during early infancy. To address this issue, a clinic
evaluation of patients with whooping cough and isolation of U. urealyticum in
their nasopharyngeal aspirates has been done. METHODS: Over a period of 11 years,
1063 nasopharyngeal aspirates from 905 infants were studied. Clinical samples
were cultured for Bordetella spp., other bacteria, viruses and mycoplasma. Data
of patients with positive cultures for U. urealyticum were obtained from clinical
records. RESULT: U. urealyticum was isolated from 26 patients with a median age
of 5 months (range: 23 days-22 months). The gestational age of 9 patients (34.6%)
was less than 37 weeks. All the patients were hospitalised because of pertussis
like syndrome, which was associated with respiratory distress due to bronchospasm
in 18 patients (69.2%). Twelve patients (46.1%) had fever and 15 (57.7%) showed
lymphocytosis. The chest roentgenogram was abnormal in 18 patients (69.2%):
pulmonary hyperaeration, with or without atelectasis. Clinical evolution was good
in all patients. In 16 patients (61.5%) U. urealyticum was isolated together with
other microorganisms: in 9 samples with bacteria (H. influenzae, S. pneumoniae,
B. pertussis, M. catarrhalis), in 5 with viruses (respiratory syncytial virus,
cytomegalovirus, adenovirus, enterovirus) and in 2 samples with respiratory
syncytial virus and S. pneumoniae and B. pertussis respectively. CONCLUSIONS:
Likely U. urealyticum cannot be considered clearly as the etiologic agent of
whooping cough, mainly because in the 61.5% of patients U. urealyticum has been
isolated together with other microorganisms considered pathogens or potentially
pathogens. Future studies would be necessary in order to establish the pathogenic
role of U. urealyticum after the neonatal period.
PMID- 11003901
TI - [Analysis of treatment failure in pediatric subglottic stenosis].
AB - BACKGROUND: The good results obtained until nowadays in the surgery of subglottic
stenosis is followed by an analysis of the failures. METHODS: We study
retrospectively 48 cases treated in the last eight years in two institutions.
Study variables were: age, previous diagnosis, grade os the stenosis, surgical
treatment, complications and evolution. RESULTS: Mean age was 2.8 +/- 0.43 years
(newborn-17 years). In 13 cases (27%) the result obtained was considered a
failure. Failure indexes were: treatment selection (7,7%), surgical technique
selection (23%), due to the technique itself (23%), iatrogenia (15,4%),
associated diseases (30,7%). Mortality of the series was 8.3%. CONCLUSIONS: The
learning curve of these techniques is difficult although once the necessary
experience is achieved the results are excellent.
PMID- 11003902
TI - [Experience with ventriculitis at a neonatology department].
AB - OBJECTIVE: To study the characteristics, treatment and follow-up of patients with
ventriculitis in our neonatal unit. PATIENTS AND METHODS: Retrospective study of
patients diagnosed with ventriculitis from January 1990 to December 1997.
Diagnostic criteria were the identification of any bacteria in the ventricular
fluid and pleocytosis (> or = 100 leukocytes per microl). Personal history,
clinical and analytical findings and evolution after diagnosis were studied.
RESULTS: We recorded ten cases of ventriculitis in nine patients. Six of them
occurred as a complication of previous meningitis and four occurred after
neurosurgical treatment. The mean age at diagnosis was of 38.8 days (range 8
130), and mean gestational age was 29.4 weeks (range 25-38). Clinical and
ventricular fluid anomalies were seen in six cases and in four the diagnosis was
made at autopsy. Treatment was systemic antibiotics. In two cases
intraventricular antibiotics were added. Six patients died, ventriculitis being
the direct cause of death in five. Of the three survivors, one had mental
retardation and cerebral palsy and the other two had minor disabilities.
CONCLUSIONS: During the neonatal period, a high degree of clinical suspicion and
techniques for an early diagnosis and treatment are needed for ventriculitis.
PMID- 11003903
TI - [Oxidative phosphorylation defects with neonatal presentation: review of our
caseload].
AB - OBJECTIVES: To define the oxidative phosporilation deficit syndrome in the
neonatal in terms of incidence and clinical, biochemical and genetic features.
MATERIAL AND METHODS: We report 9 newborns diagnosed as oxidatic phosporilation
deficit during the last 8 years in our hospital by means of clinical, metabolic,
pathological and molecular studies, among other evaluations. The diagnosis was
established based on ensymatic deficit of the respiratory chain, associated with
alterations in the mtDNA in one case, and with mitochondrial ultrastructural
anomalies in 5 cases. RESULTS: There was an incidence of 1/3.555 newborns and
1/832 newborns admitted in our Neonatal Unit. In four of them there were familial
antecedents and polihidramnios in two. Most of them, 8 out of 9, were born at
term after a normal pregnancy and delivery, with normal Apgar score and
auxological examination. Symptomatology started immediately at the neonatal
period as acute neurological damage in most of them. There was a severe evolution
as 5 children died and 4 survived with severe damage. All of them had the
classical phenotype of early severe encefalopathy, associated with dismorphic
features, hypotomia, neurosensorial defects, brain dysgenesis and atrophy,
anomalies in the EEG and in 5 of them there were also systemic anomalies, mainly
cardiopathy. The most frequent biochemical alteration was a significative
increment of the quotient lactate/piruvate. Five patients presented
ultrastructural alterations of the mitochondria in thr muscle biopsy but Cox
stain was not positive in any case. Three cases has a deficit of the complex IV,
e of the complex I-IV, 2 of the complex I and one the complex I-III-IV. Only one
patient had multiple deletions in the mtDNA. CONCLUSIONS: Oxidatic phosporilation
deficit are frequent and severe diseases of prenatal onset with limited fetal
effects, homogeneous clinical phenotype with frequent damage of the central
nervous system and variable extraneurological alteration and inconsistent
biochemical pattern. Enzymatic studies ar need for making the diagnosis in all
suspected cases,
PMID- 11003904
TI - [Adolescents with growth retardation].
PMID- 11003905
TI - [Toxic shock syndrome in children. Report of four cases].
AB - We report four children with toxic shock syndrome admitted in the pediatric
intensive care unit of our hospital during the past year. All the children had
the five criteria established by the Centers for Disease Control for the
diagnosis of this syndrome. In all four there was a probable point of entry of
the infection: maxillar sinusitis in one, pneumonia in two and surgical wound in
the other. No bacteria that could have caused the infection were isolated in any
of the children, which suggests a staphylococcal origin for this syndrome.
Evolution was good in all of the children due to aggressive treatment that
included inotropic support, volemic expansion and antibiotics. Two of the
children, who suffered adult respiratory distress syndrome, required prolonged
respiratory support.
PMID- 11003906
TI - [Isolated hyperferritinemia in a healthy male infant: hereditary
hyperferritinemia-cataract syndrome].
AB - The case of a male infant who was found to have hyperferritinemia was made at the
age of 3 months is described. The patient and several members of his family from
three generations were diagnosed with hereditary hyperferritinemia-cataract
syndrome with a new point mutation in the iron-responsive element of the L
ferritin gene. Differential diagnosis of hyperferritinemia is discussed with
emphasis on the need for the knowledge of this entity to avoid unnecessary
investigations.
PMID- 11003907
TI - [Traumatic pulmonary pseudocyst].
AB - Traumatic pulmonary pseudocyst is an unusual complication that appears after a
closed thoracic trauma. It is produced as a consequence of outburst and shear
forces released by the impact on the elastic thoracic wall. We present a 14-year
old boy who, after a motorcycle crash, presented a traumatic pulmonary
pseudocyst, isolated on the right hemithorax. The patient's evolution was good.
The antecedent of trauma, together with radiological examination and the tendency
toward spontaneous resolution, suggested the diagnosis as well as the
advisability of a conservative approach in most pediatric cases. Recognition of
this unusual disorder would help to avoid unnecessary diagnostic and therapeutic
procedures.
PMID- 11003908
TI - [Acute interstitial nephritis of probable pharmacological origin].
AB - Acute interstitial nephritis in children is rare. We present a case of acute
interstitial nephritis in a 10-year-old boy, which was probably drug-induced.
Initial symptoms included fever, loss of appetite, weight loss, alterations in
urine analysis and mild renal failure. Treatment with steroids produced a good
clinical response and renal function returned to normal within a few months.
PMID- 11003909
TI - [Focal nodular hepatic hyperplasia. A report of a new case].
AB - Focal nodular hyperplasia is a benign liver tumor, that is rare during childhood.
We report a new case, exceptional by the short age of the patient, and by the way
of this we review the epidemiology, the actual diagnosis criterion and the
treatment options.
PMID- 11003910
TI - [Use of intrapleural urokinase in children].
AB - OBJECTIVE: To present the use of intrapleural urokinase as an alternative to
surgical management of complicated pleural effusions in children. To add new
cases to the literature and set bases for the development of a standardized
protocol. METHOD: Presentation of three cases in children under three years of
age treated with intrapleural urokinase. RESULTS: Resolution of the effusions
with lack of adverse effects. CONCLUSION: Treatment of pleural effusions when
loculations develop. This invasive approach might be avoided in some cases by
instillation of a fibrinolytic agent such as urokinase into the pleural space,
this being an efficient and safe procedure.
PMID- 11003911
TI - [Phenotype heterogeneity in Gitelman's syndrome].
AB - A family with three offspring affected of Giltelman's syndrome is reported. The
phenotypic variability of this entity is emphasized. Moreover, the diagnosis
criteria of the syndrome, phathophysiology, and genetics and clinical differences
with Bartter's syndrome are stated.
PMID- 11003912
TI - [Cohen's syndrome: non-causal association with vascular rings].
AB - Cohen syndrome is an autosomal recessive disorder characterized by hypotonia,
mental retardation, microcephalia, typical craniofacial features, myopia and
chorioretinal dystrophy. The responsible gene has been mapped to chromosome 8q 22
(COH 1). Since it was described more than 100 patients have been reported.
However, none of them has been associated with vascular rings. Our hospital has
studied eight pediatric cases and 25% of them were related with vascular rings.
PMID- 11003913
TI - [Use of the International Classification of Epilepsies and Epileptic Syndromes in
epidemiologic studies].
PMID- 11003914
TI - [International classification of the epilepsies and epileptic syndromes in
epidemiologic studies] [In Process Citation]
PMID- 11003915
TI - [Erythema nodosum associated with Salmonella enteritidis infection].
PMID- 11003917
TI - [ [In Process Citation]
PMID- 11003916
TI - [Neonatal papular acrodermatitis (Gianotti-Crosti) and Bartonella henselae
infection].
PMID- 11003918
TI - [Imported malaria in children].
PMID- 11003919
TI - [Imported malaria in children (1993-1998)].
AB - Malaria is the world's most important parasitic infection, accounting for an
estimated 300 million cases and 1.5 to 3 million deaths annually. Although it has
been eradicated from temperate countries, increasing numbers of travellers visit
each year tropical countries, where malaria remains a major cause of morbidity
and mortality. Children are particularly at risk from malaria since symptoms can
be especially severe and can develop rapidly. Symptoms may differ from those in
adults and, as children often have febrile illnesses, malaria could not be
suspected. Eleven cases of imported mala-na in children which ages was between 15
month until 13 years, were seen in the Sant Joan de D|u Hospital, Barcelona
(Spain) since August 1993 until August 1998. The aetiology was in 7 cases
Plasmodium falciparum and in 4 cases Plasmodium vivax, in one case we found also
with the P. falciparum some forms of P. malariae. All of them experience fever
and anaemia at admission and nine had splenomegaly; the evolution after the
treatment was fine. Cases of imported malaria in children are increasing and it
is timely to review the prevention and the management.
PMID- 11003920
TI - [Surgical treatment of supravalvular aortic stenosis].
AB - OBJECTIVE: Surgical correction for 10 supravalvular aortic stenosis since 1988.
MATERIALS AND METHODS: Diagnosis was carried out by means of echocardiography and
magnetic resonance. Seven patients showed features of Williams-Beuren syndrome, 5
patients showed in their genotype a delection of 7-chromosome. 5 showed
membranous-localized type obstruction and the other 5 with hourglass type. The
patients in the first group underwent circumferential resection of the stenosis
ring followed by a diamond- shaped patch and the second group were treated with
resection of the stenosing ring associated with an inverted Y- shaped patch with
releasing of the coronary ostia in two of them. RESULTS: There was no hospital
death. The gradient was substantially reduced from 60 +/- 8 to 5 +/- 1 mm Hg
(range 0-14). The average staying was under 7 +/- 1 days. The average follow-up
was 58 +/- 8 months (2-120). CONCLUSIONS: Postoperatively, all the patients were
in NYHA class I-II. The residual gradient was less than 15 mmHg in the
echocardiography study during the follow-up and none of them required an
additional operation.
PMID- 11003921
TI - [Fisher's index as indicator of severity and its course in the postoperative
period following liver transplantation in children].
AB - OBJECTIVES: To study the evolution of Fisher index during the early postoperative
period after liver transplantation in children. PATIENTS AND METHODS: We have
studied 32 liver transplants performed on 26 pediatric patients, during the first
week of the post-operative period. In all cases the BCAA/AAA quotient was
determined before transplant, at the time of PICU admission, and on days 1, 2, 3,
4, 5, 6 and 7 after transplant. RESULTS: Compared to control group values, the
Fisher index for these patients is significantly lower at pre-transplant (p <
0,0001), upon admission (p < 0,001), and days 1 (p < 0,0001), 2 (p < 0,0001) and
3 (p < 0, 0001). Comparison between non-survivors and survivors shows a
significant reduction in the first group on the index in days 1 (p < 0,02), 3 (p
< 0,02), 4 (p < 0,005), 5 (p < 0,002), 6 (p < 0,03) and 7 (p < 0,01) of post
transplant. CONCLUSIONS: The evolution of the Fisher index can be useful as an
indication of the severity of the condition of these kinds of patients, which
would help to establish more aggressive treatment to improve prognosis.
PMID- 11003922
TI - [Bone mineral density and bone mineral content variations in various
communities].
AB - OBJECTIVE: To study the bone mineral density (DMO) and the bone mineral
concentration (CMO) in lumbar spine (L2 and L4) by dual-energy x-ray
absorptiometry with a lunar DPX (DEXA) in a children sample of the community of
Madrid; to relate the values obtained with the age, sex and pubertal development;
and to compare the values of DMO found with the publications of other autonomous
communities. MATERIALS AND METHODS: 351 children, 184 boys and 167 girls selected
at random in our environment. The age range oscillated between 6 months and 20
years. Grouped in intervals of a year according to the sex; and in accordance
with the pubertal development. The bone mineral content was measured by dual
energy x-ray absorptiometry with a lunar DPX in the lumbar spine at level of L2
L4. The statistic analysis has been accomplished with the SPSS version 6.0.1.
They have been obtained the average and deviation standard for each group from
studied age, and also according to pubertal development; the DMO and CMO of the
boys and girls have been compared by groups of age; the DMO and CMO within each
sex between a group of age and the immediately superior have been compared
through an analysis of the variance; the effect that the age has on the DMO and
the CMO has been evaluated and finally through multivariant analysis techniques
the regression models have been estimated between the age and the DMO, and the
age with the CMO. CONCLUSION: The DMO shows variations between the various
communities and even in different samples of a same community, in Carrascosa
study the DMO is highest, expressed in SD score, in many several groups of age
studied with respect to our values and with the values of Moreno et al and Armada
et al; the values of DMO in our study are greater than the ones found by Moreno
et al and Armada et al; the first four years and the adolescence are the periods
of maximum increase of the DMO, but it also increases in an oscillatory way in
the intermediate stages; the girls present some highest levels of DMO in the
groups of age of 12-13 and 14-15 years, probably in relationship to a most
precocious beginning of the puberty; and finally the regression line of the DMO
as compared to the age for both sexes are parallel and have equal court point,
what means that they are coincident.
PMID- 11003923
TI - [Peak expiratory flow rate in 4- to 15-year-old children. Comparison of 3
measuring models].
AB - OBJECTIVE: a) To establish the possible differences between three different
models of PEF-meter, including PF-Control for the first time; b) to build a
normogram for each of the three models, as a function of different variables
(age, height, and inspiratory and espiratory thoracic circumference); c) to
search for differences between both sexes, and d) to study the mathematical
correlation between the results yielded by the different models. METHODS: PEF was
measured in a sample of 476 school-children, in the range of 4 and 15 years (233
boys, 243 girls), with a mean age of 9,3 years and a height range between 96,8 cm
and 178,8 cm (mean 137,9). PEF value was recorded as the best of three attempts
when the difference them was less than 10%. Three devices of each model were used
(Vitalograph, Mini-Wright, PF-Control). The utilisation was always done in a
rotatory fashion at school time (15-17 hours) in the children's school. RESULTS:
We found significant differences between the three models (p < 0,0004). The best
predictive variable for PEF is height, with an r = 0,90-0,92 (depending on the
model) when the exponential model is considered. Independently of the device,
there were significant differences between sexes. CONCLUSIONS: a) The variable
that expresses PEF the better is height; b) PEF values are different between
girls and boys; c) there were significant differences between the various models;
d) Monitoring of a given child must be done with the same model of PEF-meter, and
e) The best correlation is obtained with the exponential model, although
differences with the lineal model were not statistically significant.
PMID- 11003924
TI - [Insulin Lispro (Lys B28, Pro B29) treatment in adolescents and young people with
type 1 diabetes].
AB - BACKGROUND: The human insulin analogue, Lispro (Lys B28, Pro B29), is more
similar to normal pancreatic insulin response to ingestion. Therefore, it could
provide an alternative to the classical treatment of type-1 diabetes in
childhood. The aim of this study was to analyze the response to insulin treatment
with this analogue during 1 year. PATIENTS AND METHODS: In a study group of
twenty puberal diabetic patients (nine male and 11 female) with a mean age of
15.6 years (+/- SD) and with diabetes of a mean of 8.3 years (+/- 4.3 SD),
classical intensive treatment, a combination of regular insulin (HR) and NPH
insulin (Humulin NPH) was substituted for a new treatment with Lispro and NPH
insulin in 3-4 doses. All patients had received diabetic education and performed
at least four blood glucose tests daily and self monitoring. We analyzed the 6
months prior to the change in treatment (Group A) and the 12 months after the
change (Group B). The amount of insulin (u/kg/day), the fast/intermediate insulin
ratio in each dose, dietary modifications, the level of metabolic control given
by the HbA1C average measured every 2 months, severe hypoglycemia and the patient
s level of satisfaction with the new treatment were compared between the two
groups. RESULTS: The number of daily doses, as well as the daily insulin intake,
was the same in both groups (3.7 [+/- 0.6] doses/day; 0.9 [+/- 0.2] u/kg/day).
With Lispro treatment the ratio fast/intermediate insulin was reduced. This
reduction was statistically significant for the pre-breakfast dose (Classical =
65. 4 +/- 30% vs Lispro = 47.1 +/- 19.6%), and for the pre-lunch dose (Classical
= 58.1 +/- 29.3% vs Lispro = 39 +/- 12.8%). Most patients did not need neither
mid-morning or mid-afternoon doses. There were no modifications in body mass
index. Although metabolic control improved slightly (Classical X A(b) A(1)c = 7
+/- 1.2 vs Lispro X A(b) A(1c) = 6.6 +/- 1.1), the difference was not
statistically significant. Three patients had a severe hypoglycemic episode in
the first 6 months with the new treatment pattern. All of them were satisfied
with the new insulin. CONCLUSIONS: Intensive therapy with Lispro insulin combined
with appropriate doses of basal insulin (NPH) can provide a good alternative in
the treatment of diabetic teenagers.
PMID- 11003925
TI - [Use of a hospital pediatric emergency department during the night].
AB - OBJECTIVE: To determine the characteristics of children younger than 14 years
visiting our pediatric emergency department between 0:00 and 8:00 hours. PATIENTS
AND METHODS: Retrospective review of 300 children visiting our emergency
department at night. RESULTS: Between March 1 and 22 1999 we recorded 300
episodes from 0:00-8:00 hours (1.7 patients/hour) and 2350 episodes from 8:00
24:00 hours (6. 6 patients/hour). Of the 300 episodes registered at night, 132
children (44%) came between 0:00 and 2:00. The most common complaints were:
respiratory symptoms in 116 patients (38.6%), fever in 61 (20.3%) and digestive
symptoms in 61 (20.3%). We carried out at least one complementary test in 111
patients (37.0%). Five children (1.7%) were admitted to the hospital (80 between
8:00 and 24:00, 3.4%, p = 0.15) and 25 (8.3%) were admitted for a few hours to
the observation ward (123 of the 2350 who came between 8:00 and 24:00, 5.2%, p =
0.06). Final diagnoses were: ear nose and throat infection in 91 (30.3%), fever
without source in 38 (12.6%), asthma in 29 (9.6%), acute gastroenteritis in 27
(9%), croup in 22 (7.3%), vomiting in 14 (4.6%), abdominal pain in 13 (4.3%),
febrile convulsion in 6 (2%), pneumonia in 5 (1.6%), bronchiolitis in 5 (1. 6%),
bacteremia in 1 (0.3%), and other diagnoses in 46 (16.3%). CONCLUSIONS: The
number of visits to our emergency department diminished at night, particularly
between 0:00 and 2:00. The night-time admission rate was less than the daytime
rate, although this difference was not statistically significant. Admission for a
few hours to the observation ward was more common at night. The percentage of
patients with respiratory illnesses was higher during the night.
PMID- 11003926
TI - [Survival at discharge of newborn infants weighing less than 1000 g (1991-1997).
When are they too small?].
AB - OBJECTIVE: To describe survival rates at discharge in liveborn infants with birth
weight under 1000 g by birth-weight and gestational age categories in a third
level spanish hospital in order to improve health care planning and parental
counselling about the threshold of viability. STUDY DESIGN: A follow-up study of
178 infants with birth-weight under 1000 g born alive between 1991 at 1997. Six
newborns with lethal malformations were not included. RESULTS: Overall survival
at discharge was 54%. During the study period survival rate improved in the birth
weight group 750-999 g. In the group below 750 g survival rate was lower and
improved more slowly. Survival rate for infants below 750 g and 26 weeks was
extremely low. Over 749 g and 25 weeks survival was over 50%. CONCLUSIONS:
Survival rate showed an improving trend during the study period. In the last
years of the study period survival in infants with birth-weight over 749 g was
above 85%. For infants under 750 g and 26 weeks was extremely low. Family and
medical decision making about active treatment of these newborns should be an
individualized process.
PMID- 11003927
TI - [Limb reduction defects in Asturias (1986-1997): prevalence and clinical
presentation].
AB - AIM: To determine the prevalence and clinical presentation of limb reduction
defects in Asturias (Spain). PATIENTS AND METHODS: Among the 92300 newborns,
stillbirths and induced abortions for congenital defects surveyed by the Registry
of Congenital Defects in Asturias (population-based registry) during 1986-1997,
we studied the children with limb reduction defects. Frequency is expressed as
total prevalence per 10000 births. RESULTS: Seventy-three children with limb
reduction defects were identified, with a total prevalence of 8 per 10000 births
(CI 6.2-9.8): upper limbs were affected in 65.7%, lower limbs in 23.3% and both
upper and lower limbs were affected in 11%. Transverse terminal defects were
present in 49.3%, and were intercalary in 16.4%, preaxial longitudinal in 8.2%,
postaxial longitudinal in 9.6%, split hand/foot in 9.6% and multiple in 6.8%.
Limb deficiencies were found in 52%; of these, 48% were associated with other
congenital defects. Four had chromosomal anomalies and 20 were syndromes. 31% had
low birth weight for their gestational age. Alcohol exposure during pregnancy was
recorded in three mothers. CONCLUSIONS: A detailed study of limb reduction
defects could lead to a better understanding of clinical presentation and to an
etio-pathogenic diagnosis to control risk factors.
PMID- 11003928
TI - [Indications for anti-regurgitation formulas. Committee on Nutrition of the AEP].
PMID- 11003929
TI - [Facial and buttock dermatitis].
PMID- 11003930
TI - [A case of neonatal malaria in Spain].
AB - We report a case of neonatal malaria born in Spain. It is about a female newborn
whose mother lived the first eight months of her pregnancy in Ecuatorial Guinea.
Although our patient was well, in the third week of her life she developed fever
mostly in mornings without any other symptoms except pallor. She kept a good
physical state in any moment. In complementary proves we remark: anaemia and
thrombocytopenia; as well Plasmodium falciparum ruin was found in blood smears.
Treatment with mefloquine was successfully, blood smears was negative of
parasites in the eighth day and hemogram was restoring normal. This article
suggests neonatal malaria must be considered in those newborns suspected
congenital infection born from mothers who have travelled to risk countries or
immigrated from endemic areas. Also we remark that malaria clinic development in
newborns is nonspecific and indistinguishable from other congenital infections.
PMID- 11003931
TI - [Effectiveness of hemodynamic treatment guided by gastric intramucosal pH
monitoring].
AB - OBJECTIVE: To determine whether gastric intramucosal pH can be used as an
indicator for the treatment of critically ill children. METHODS: A protocol for
hemodynamic treatment was tested in 34 critically ill children (medical and
surgical patients). Endpoint was considered as normalization of gastric
intramucosal pH. Hemodynamic complications were compared with another group of
critically ill patients who received conventional treatment. RESULTS: Treatment
designed to improve tissue oxygenation (hemodynamic stabilization, volume
expansion, and dobutamine perfusion) raised pHi values from 7.25 +/- 0.04 to 7.32
+/- 0.13 (p = 0.014). Seventy-three percent of the children with pHi < 7.30
presented hemodynamic complications. These findings were compared with the
results obtained in a control group of 30 critically-ill children given
conventional treatment in the pediatric intensive care unit. In this group, 93.8%
of the children with a pHi < 7.30 developed hemodynamic complications.
CONCLUSIONS: We conclude that gastric intramucosal pHi can be useful as an
indicator for the hemodynamic treatment of critically ill children.
PMID- 11003932
TI - [Therapeutic efficacy of ketoconazole in Cushing syndrome].
PMID- 11003933
TI - [West's syndrome associated with calcified frontal dysplasia. Favorable treatment
response].
PMID- 11003934
TI - [Cystic angiomatosis].
AB - A case of cystic angiomatosis is presented in a patient whose clinical sign were
the presence of an inguinoescrotal mass due to a retroperitoneal lymphangioma,
visceral splenic lesions and diffuse skeletal lesions. This rare entity is
discussed and a brief review of the literature is made.
PMID- 11003935
TI - [Severe neonatal mitochondrial cytopathy caused by isolated COX defect].
AB - We report a neonate with isolated cytochrome c oxidase (COX) defect and severe
multisystemic involvement. The patient had severe encephalopathy, predominant
since birth, and died due to hypoxic-ischemic myocardiopathy. He was the second
son of non-consanguineous, healthy parents who also had a daughter with chronic
encephalopathy. The neonate presented dysmorphic phenotype, hepatic and muscular
involvement, and possibly tubular involvement. Metabolic studies revealed
markedly increased lactic/pyruvic concentrations. Diagnosis was based on muscular
enzymatic studies and ultrastructural mitochondrial anomalies, while the
mitochondrial DNA and results of the COX technique were normal. Histological
examination revealed a massive subendocardial infarction. Aspects of this entity
with relevance for genetic counseling are discussed.
PMID- 11003936
TI - [Median raphe cysts of the perineum in childhood].
AB - Median raphe cysts of the perineum are uncommon congenital lesions. Congenital
lesions rarely encountered in daily clinical practice. Their diagnosis in
childhood is particularly rare. We report two children with these cysts requiring
surgical removal. We review the embryological, diagnostic and therapeutic aspects
of these cysts, which could be of interest to pediatricians and pediatric
surgeons when faced with this pathology in children.
PMID- 11003937
TI - [Cervical spondylodiscitis in an infant].
AB - Spondylitis in childhood is rare, presenting a great variety of symptoms that are
related to the child s age and to the site of the inflammatory process. We
present the case of a nine-month-old infant, who presented to the emergency
department with a torticollis of six weeks evolution. The diagnosis of
spondylitis (C6-C7) was confirmed by MRI. Intravenous antibiotic therapy was
administered. The patient showed complete regression of symptoms and imaging
tests were normal. The rarity of this disease in patients in this age group, as
well as the site and form of presentation are emphasised as is the importance of
diagnosing this disease to prevent permanent neurological injuries or bone
deformities.
PMID- 11003938
TI - [Orofaciodigital syndrome associated with agenesis of the pituitary gland].
AB - Oral-facial digital syndrome (OFDS) consists of a group of heterogeneous genetic
disorders with different patterns of inheritance. These disorders share facial,
oral and digital abnormalities. At least 11 types of this syndrome have been
described (I-IX) and the association between OFDS type II and absent pituitary
has recently been reported in the case of two brothers. OBJECTIVE: 1. To describe
the case of patients with OFDS associated with the absence of the hypophysis and
panhypopituitarism. 2. To analyse whether the association between the agenesis of
the hypophysis with OFDS represents a new type of this syndrome. PATIENT: An 11
month-old male infant presented with a malformation syndrome with oral (Gothic
palate, lobulated tongue with lateral frenulae and hamartomas) facial (a small
nose with flattened nasal root and hypoplastic nostrils, small facial skeleton,
high forehead, low-implanted ears, stenosis of the choana) and digital
malformations (poly- and clinodactyl hands and feet) typical of OFDS. In addition
to these findings, at the age of 11 months he had growth retardation (length -
5.9 SD), obesity, mild psychomotor delay, a single upper incisor, micropenis and
undescended testes. Endocrinologic studies showed combined GH, TSH, LH and FSH
deficiency. Cranial magnetic resonance imaging showed a smooth sella turcica,
lacking the pituitary gland, and the absence of the normal sign of
neurohypophysis. Replacement therapy with GH and 1-thyroxine was started.
SUMMARY: We report a patient with the clinical characteristics of OFDS type II,
associated with the absence of hypophysis and panhypopituitarism. CONCLUSION: The
infrequent association of agenesis of the pituitary gland and panhypopituitarism
with OFDS, and the previous report of two brothers with this syndrome and the
same association, suggests that this is a new type of OFDS.
PMID- 11003939
TI - [Acute bulbar palsy due to myelomeningocele and Chiari II malformation].
AB - We describe a case of a 10-year-old girl with myelomeningocele and type II Chiari
malformation. She presented with an acute bulbar palsy requiring mechanical
ventilation. Surgical decompression of the brainstem was performed and, because
of a phrenic nerve palsy, surgical plication of the right diaphragm was also
required. The patient s evolution was favourable. We discuss the various forms of
clinical presentation of this pathology as well as its management. The importance
of early diagnosis and surgical correction are also stressed as a key factor for
favourable evolution.
PMID- 11003940
TI - [Renal biopsy and kidney diseases].
PMID- 11003941
TI - [Indications for renal biopsy in idiopathic nephrotic syndrome in children.
Results of a national survey].
AB - BACKGROUND: The role of the renal biopsy in children with nephrotic syndrome is
controversial, especially in patients with frequent relapses or corticosteroid
dependent nephrotic syndrome. METHODS: We have sent a survey about the nephrotic
syndrome to all the Spanish pediatric nephrologists who are members of the
Spanish Association of Pediatric Nephrology. The survey is based in 7 questions
about biopsy utility in the different circumstances of the illness. RESULTS: The
survey reveals a scarce participation, 50%. The 85% of the inquired people uses
the same diagnostical criterion. Referring the indication of renal biopsy in this
disease, the 85% considers that it would be necessary to do it in case of
corticosteroid resistance. The 57.7% of pediatric nephrologists would recommend a
biopsy in children with frequently relapsing or corticosteroid-dependent
nephrotic syndrome prior to cytotoxic therapy. The 33% doesn't practice biopsy
before cytostatic administration, only when alterations in the renal function
appear during the treatment. The 50% of the inquired considers that less than a
year of age is an indication of biopsy in the nephrotic syndrome, and the 24.4%
thinks that the age should never be an indication. CONCLUSIONS: The surveys
aren't much used in our country as a resource of information. We think that the
participation of expert people in the surveys gives validity to the obtained
results. There are different opinions among pediatric nephrologists concerning
the biopsy in children with frequently relapsing and corticosteroid-dependent
nephrotic syndrome.
PMID- 11003942
TI - [Burnout among Spanish pediatricians specialized in intensive care].
AB - BACKGROUND: The burnout syndrome is characterized by emotional exhaustion,
depersonalization and decrease or loss of the feeling of personal accomplishment.
It is frequent in the helping professions where an intense involvement with
people needing assistance occurs. In its origin, the work policy factors seem to
be important. METHODS: 68 pediatric intensive care physicians of the Intensive
Care Section of the Spanish Pediatric Association participate in the study. A
general questionnaire and a Spanish version of the Maslach Burnout Inventory was
used. The statistical analysis includes: a descriptive analysis, the Student t
test, and the analysis of the variance. RESULTS: Burnout scores were in the
average range (41,9 +/- 7,5), with a more important grade in the decrease of
personal accomplishment dimension (18,9 +/- 3,5). The 55,9% of the responders
attributed to the conflict with the managing policy, their work unsatisfaction
and the 58,8% planned to leave the job in the future. CONCLUSIONS: The importance
of burnout and its three dimensions in the health professions and in the hospital
setting is stated. It is enhanced that even though the burnout scores were in the
average range more than half of the population studied were considering to leave
their work in the future.
PMID- 11003943
TI - [Dermatomyositis in childhood].
AB - AIM: The aim of this study is to review the presenting signs and symptoms,
laboratory findings and therapeutic regimens of juvenile dermatomyositis in a
tertiary hospital. METHODS: We reviewed retrospectively the available medical
records of patients who met the clinicopathologic criteria of Bohan and Peter for
definite juvenile dermatomyositis. They were followed between 1986 and july 1999
at the pediatric rheumatology section at our institution. RESULTS: The patient
population included 3 male and 6 female patients. The mean age at diagnosis was 7
years. Clinical features demanding medical attention at the hospital were: muscle
weakness and pain, with associated general symptoms in 4 cases; isolated muscle
weakness in 2 cases; muscle weakness associated to general symptoms in 1 case;
and monoarthritis in another case. One patient presented initially only with
cutaneous rash. Three patients developed calcinosis. Serum CPK and LDH levels
were elevated in 8 patients, aldolase in 7 and aminotransferases in 6.
Autoantibodies were undetectable in all the patients. Electomyography
demonstrated myopatic or mixed pattern in the 5 patients it was practiced. Muscle
biopsy showed features of inflammatory myopathy in all the cases. Seven patients
were treated exclusively with steroids and 2 patients with steroids, methotrexate
and intravenous gammaglobuline. Actually, 6 patients are asymptomatic, 2 have
mild muscle weakness, and 1 has died. CONCLUSIONS: The results of our review
agree with other series reported. Juvenile dermatomyositis suspicious should be
made upon muscle weakness and general symptoms. Treatment with steroids should be
started promptly.
PMID- 11003944
TI - [Proposed protocol for the study of cerebrovascular disease in childhood].
AB - AIM: The etiology of cerebrovascular disease in the paediatric population,
remains unknown in up to 40% of the cases ("idiopathic"), but recent advances
could improve this percentage. We devised a comprehensive study protocol for such
investigation aimed at the identification of potentially modifiable risk factors
for paediatric stroke. PATIENTS AND METHODS: From the 141 patients initially
registered in our data base for stroke population (from January 1984 until
December 1995), we invited all the patients with idiopathic cerebrovascular
disease to complete the study protocol. New cases appeared from January 1996
until July 1999 were also included. RESULTS: A total of 68 cases were identified.
We found an etiology in 38% and in 76% of the cases we found at least one risk
factor for stroke. Mild hyperhomocysteinemia was the most frequent risk factor
identified (36% of patients versus 5% of controls), one of them an infant with
fatal haemorrhagic infarct with classic homocystinuria. 31% of the patients had
thrombotic risk factors (protein S, protein C, antithrombine III deficiency,
factor V Leiden, etc). 17.6% had unspecific febrile illness at the time of the
cerebral infarction and 11.6% had minor head injuries before the stroke.
CONCLUSIONS: The use of the protocol improves the identification of potentially
modifiable risk factors for stroke in childhood and may serve as a practical
guideline for clinicians. The stroke protocol is as important as management
strategies for acute stroke or for recurrence prevention, currently under
consideration in the adult population.
PMID- 11003945
TI - [Lipid profile in children from Rivas-Vaciamadrid. Two-year follow-up].
AB - AIM: Evaluate the lipid profiles in children after two years of follow-up.
METHODS: Longitudinal cohort study. A two years follow-up of a group of children
since they were 6 years old. Blood analysis were carried in every children
measuring total cholesterol, triglycerides, cLDL, cHDL, apoproteins A and B. It
also included TD/cHDL, cLDL/cHDL, Apo B/A ratios and atherogenic index. RESULTS:
200 mg/dl, cLDL > 135 mg/dl and Apo B > 100 mg/dl in the follow-up was of 9.51,
5.18 and 8 for those children who had in the initial study these same values. The
values of lipid profile and of the index studied improved in the two years of
follow-up. This improvement has an statistical signification only in men.
CONCLUSIONS: There is a significant correlation between the values of the lipid
profile and the index measured in those children who were six years old in the
beginning of the two years follow-up.
PMID- 11003946
TI - [Blood pressure in childhood and adolescence. Its relationship with growth and
maturation variables].
AB - AIM: To analyze the relationship between blood pressure in childhood and
adolescence and different variables including gender, age, weight, height, body
mass index and sexual maturation. METHODS: Cross-sectional study conducted in
1278 boys and girls aged 6 to 18 years old. Two blood pressure measurements were
obtained. Mean value in the two measurements was obtained for each of the
pressures: systolic (SBP), diastolic IV (DBPIV) and diastolic V (DBPV). Simple
and multiple regression analysis were done to evaluate association between
variables. RESULTS: 14 years 0.33; SBP boys > 14 years 0.34; DBPIV 0.25; DBPV
0.24) and height (SBP 6-13 years 0.33; SBP girls > 14 years 0.23; SBP boys > 14
years 0.29; DBPIV 0.25; DBPV 0.24) than for age (SBP 6-13 years 0.27; SBP girls >
14 years 0.17; SBP boys > 14 years 0.15; DBPIV 0.23; DBPV 0.22) for each of the
blood pressures. Multiple regression analysis demonstrated a significant
association between body mass index, height and SBP in the group of boys and
girls aged 6-13 years old. No other significant associations were obtained.
CONCLUSIONS: Blood pressure values in childhood and adolescence show a positive
association with growth and maturation variables. It's of capital importance to
considerate not only age, but also height, weight and body mass index when
evaluating the blood pressure value of a child.
PMID- 11003947
TI - [Aplasia cutis congenita in a newborn: etiopathogenic review and diagnostic
approach].
AB - Aplasia cutis congenita is a rare condition characterized by the congenital
absence of epidermis, dermis and, in some cases, subcutaneous tissues. It was
first described by Cordon in 1767 and more than 500 cases have been reported
since, with an estimate incidence of 3 in 10,000 births. The lesions may occur on
any body surface although localised agenesis of the scalp is the most frequent
pattern. In approximately 20% of cases underlying bone defects are also found.
Aplasia cutis congenita occurs as an isolated defect or with other associated
anomalies. There is no unifying theory for the pathogenesis and large scalp
defects present a management dilemma. We report a newborn with a large scalp
defect in the midline at the vertex without associated malformations. There was
no significant family history. Skull and extremities radiographs, chromosome
analysis, cerebral and abdominal sonography were normal. Two methods of treatment
were used: a conservative approach consisting of daily antiseptic dressing to
allow scalp epithelialization improved conditions for secondary surgery at 30
days of life, closing the defect with local rotational flaps. The postoperative
course was uneventful and an excellent cosmetic result was achieved.
PMID- 11003948
TI - [Delayed presentation of Bochdalek hernia associated with Hirschsprung disease].
PMID- 11003949
TI - [Congenital hepatic fibrosis and autosomal recessive polycystic kidney disease].
PMID- 11003950
TI - [Adrenocortical suppression after high doses of inhaled fluticasone].
PMID- 11003951
TI - [Reye-like syndrome as initial manifestation of mitochondrial disease].
PMID- 11003952
TI - [Magnetic resonance in a case of a newborn with pulmonary valve agenesis and
deletion of chromosomal region 22q 11,2].
PMID- 11003953
TI - [Transhepatic cardiac catheterization in children. Report of one case].
PMID- 11003954
TI - [What is your diagnosis? Bloody diarrhea].
PMID- 11003955
TI - [What is your diagnosis? Causal image in an abdominal radiograph].
PMID- 11003956
TI - [Evidence-based paediatrics].
PMID- 11003957
TI - [Correlation between high plasma viral load and levels of TNF-alpha and cICAM-1
in HIV-1 infected children].
AB - AIM: To assess the relationship among plasma TNF-a and cICAM-1 levels and plasma
viral load (VL) in HIV-infected children and to compare these values with those
of healthy non-HIV infected children. PATIENTS AND METHODS: We studied 44 HIV
infected children and 38 non-HIV-infected children. The VL was quantified using
standard molecular assay. CD4 and CD8 lymphocyte subpopulations were determined
by flow cytometry. TNF-a and cICAM-1 were quantified using commercially available
specific enzyme-linked immunosorbent assay (ELISA). RESULTS: Levels of TNF-a and
cICAM-1 were higher in HIV-infected children than in non-HIV infected children.
HIV-infected children with VL > 50000 copies/ml had higher levels of TNF-a
(12.83; 95% CI: 24.71 to 0.95 pg/ml) and cICAM-1 (248.94; 95% CI: 419.01 to 78.84
ng/ml) than HIV-infected children with VL < 50000 copies/ml. Interestingly, we
found an increase of 6.57 pg/ml of TNF-a and 119.97 ng/ml of cICAM-1 levels for
each log10 of VL. CONCLUSIONS: HIV-infected children had higher levels of TNF-a
and cICAM-1 than healthy controls. Our data indicate a positive correlation among
plasma TNF-a and cICAM-1 and VL levels.
PMID- 11003958
TI - [Bone mineral density in juvenile-onset diabetes mellitus].
AB - OBJECTIVE: To determine bone mineral density (BMD) at axial and appendicular
sites in patients with type 1 diabetes mellitus and evaluate its relationship
with metabolic control and disease duration. PATIENTS AND METHODS: BMD was
measured by dual-energy X-ray absorptiometry (Hologic QDR-1000) in the lumbar
spine (L1-L4) and at the distal third forearm in 246 healthy non-diabetic
children and adolescents (111 boys, 135 girls, aged 2.8-20.8 years) and in 45
diabetic patients (18 boys, 27 girls, aged 5.2-19.4 years). The results were
expressed as the mean and standard deviation. The differences were tested by
analysis of variance or Students t-test, as appropriate. The relationship between
BMD and the remaining variables was studied by simple Pearsons coefficient and
partial correlation coefficient. Significance was defined as p < 0.05. RESULTS:
BMD Increased progressively from infancy to adulthood In both populations. Lumbar
spine and forearm BMD were significantly lower in diabetic patients than in the
healthy non-diabetic children, mainly during pubertal spurt. The greatest
differences were found in males and in the trabecular bone. No relationship was
found between metabolic control (mean glycosylated hemoglobin, insulin
requirement) and duration of diabetes and the BMD in any region studied (p >
0.05). CONCLUSIONS: Pediatric patients with type 1 diabetes mellitus appear to
constitute a population at risk of osteoporosis in adult-hood. Diagnosis of
osteopenia diagnosis should be established according to densitometric criteria.
In this study, metabolic control parameters and duration of diabetes did not
enable predetermination of diabetic patients at risk of osteoporosis in
adulthood.
PMID- 11003959
TI - [Respiratory function in pediatric survivors of malignant neoplasms].
AB - AIM: To evaluate post-treatment pulmonary function in patients with malignant
extrapulmonary neoplasia and its relationship with age, type of neoplasty and
treatment received. METHODS: Cohort study of 95 pediatric patients after
chemotherapy with or without surgery or extrapulmonary thoracic radiotherapy. The
patients were in remission without treatment and able to undergo pulmonary
function testing. Personal history and exposure to risk factors or toxic habits
were evaluated. Clinical examination, chest radiographs, pulmonary gammography,
basal and stress pulmometry, forced spirometry, whole body phletismography and
carbonmonoxide transfer test were performed. RESULTS: Mean age at diagnosis was 5
+/- 3.3 years. Treatment duration was 2.4 +/- 1.3 years and time without
treatment 4.3 +/- 3. 3 years. Thirty-six patients were reviewed two and a half
years after the first control. Thirty-nine patients had acute lymphoblastic
leukemia and 57 had solid tumors. Sixty percent showed functional restriction due
to chest deformity after undergoing chest surgery. The association between
functional restriction and radiotherapy (6 patients) did not produce poorer
functional results. Forty-three percent showed initial change in TLCO. Nineteen
percent showed basal hemoglobin saturation under 93% which in 16% fell after
physical exercise. These alterations improved with time. However, restrictive
change initially present in 11.5% persisted at the second evaluation. Thoracic
surgery was the main cause of thoracic deformity and therefore of restrictive
change. The children under 8 years old and those who received longer treatments
tended to show the worst TLCO values. The patients with neuroblastoma showed
greater restrictive change while the change in TLCO was more frequent in patients
with Burkitt s lymphoma and in those treated with cyclophosphamide. CONCLUSIONS:
Neither personal or family history of respiratory disease nor the presence of
symptoms such as cough served to identify risk of functional change. Restrictive
change in pulmonary function was greater in patients who had undergone thoracic
surgery. Functional values were worse in patients with neuroblastoma. Pulmonary
function should be followed up in pediatric survivors of malignant neoplasia in
order to prevent restrictive alterations.
PMID- 11003960
TI - [Food habits and dietary intake during the first year of life].
AB - OBJECTIVE: To determine feeding habits and dietetic ingestion du-ring the first
year of life and to assess whether these are in accordance with dietetic
recommendations. PATIENTS AND METHODS: A total of 171 healthy infants between 1
and 12 months old were studied. Two types of inquiry were carried out: 24-recall
and weekly frequency of food. RESULTS: The percentage and duration of
breastfeeding was low. Feeding with cows milk was more frequent than with breast
milk from the age of 3 months. Thirty-eight per-cent of children had whole cows
milk from the age of 6 months. Complementary feeding was introduced in accordance
with international recommendations. The ingestion of energy and nutrients was
also in accordance with the recommendations of the RDA during the first 6 months
of life. In children aged 6-12 months, energy in-take was sufficient but diets
were high in proteins and II-pIns and fairly high in carbohydrates. CONCLUSION:
Ingestion of micronutrients and minerals are higher than is recommended except in
the case of zinc.
PMID- 11003961
TI - [Intellectual development in the second year of life in healthy breast-fed
children compared with formula-fed children].
AB - BACKGROUND: The role of breast milk with regard to W3 long-chain polyunsaturated
fatty acids and infant intellectual development remains controversial. PATIENTS
AND METHODS: Thirty-nine children born at term and from homogeneous sociocultural
status were enrolled in a blind-prospective trial. Children were divided in two
non-randomized groups: a breast-fed group and a standard formula-fed group. Red
blood cell phospholipid fatty acids were analyzed at 7 and 60 days of life.
Cognitive development was evaluated at the end of the second year of life through
Bailey s test. RESULTS: Concentrations of phosphatidylethanolamine and
phosphatidylcholine docosahexaenoic acid were significantly lower in the formula
fed group. No statistically significant differences between groups were found in
cognitive function. Brain development index was significantly correlated with
infant head circumference and educational status of the mother. CONCLUSIONS:
Maternal nutrition provides higher red blood cell docosahexaenoic acid, but is
not related to a higher developmental quotient at the age of 2 years. However,
infant head circumference and maternal educational status were correlated with
developmental cognition.
PMID- 11003962
TI - [Admissions of patients with AIDS to pediatric intensive care units].
AB - OBJECTIVE: To describe the most significant clinical features of children with
acquired immunodeficiency syndrome who required admission to a pediatric
intensive care unit (PICU). METHODS: Retrospective study of 12 patients with AIDS
who required 13 admissions, between January 1988 and December 1997. RESULTS: Mean
age at admission was 15 months (1 month-6 years). Seven patients were under 1
year of age; four were diagnosed during their stay in the unit. The most common
reason for admission was respiratory failure (six patients), followed by cardiac
failure. Six patients needed mechanical ventilation (5 for respiratory failure).
Two patients died during their stay, one of pneumonia due to Pneumocystis carinii
infection and one of septic shock. CONCLUSIONS: One-third of patients was
diagnosed with HIV Infection during their stay at the PICU. Opportunistic
infection was the initial manifestation of the disease. Consequently, with this
type of infection, clinical suspicion should be high. The survival rate of up to
84.6% of the admissions to our unit as well as the new, highly active
antiretroviral therapy, generally make HIV-infected children suitable for
treatment in intensive care units.
PMID- 11003963
TI - [Children's unscheduled return visits to an emergency department].
AB - OBJECTIVE: To study the patients who make unscheduled return vi-sits in less than
week to a pediatric emergency department (ED). PATIENTS AND METHOD: Retrospective
review of 495 episodes in 233 children who were attended at our ED in November
1999. RESULTS: In November 1999, we registered 3667 episodes at our ED (495
corresponding to 233 children who made repeat visits, 13.4%). The most common
chief complaints among children who revisited were fever and respiratory
symptoms. The most common diagnoses were fever with-out apparent source, ORL
infections, asthma and acute gastro-enteritis. The diagnoses made at the initial
and fi-nal visits were the same in 131 cases (56.2%), a complication was detected
in 18 (7.7%) and 84 (36.1%) were given a different diagnosis. The percentage of
patients who received a symptomatic diagnosis was lower in the final visit. The
admission rate of children who revisited was higher than that of children who
visited our ED once (6.4% vs. 3.0%, p = 0.009), caused by the group of patients
who received a different diagnosis when they revisited our ED. CONCLUSIONS:
Patients who revisit a pediatric ED within a week are more likely to be admitted
to the hospital, especially if the diagnosis they receive varies.
PMID- 11003964
TI - [Abused children. Role of the pediatrician].
AB - Child maltreatment, in it's different forms (physical, negligence, Munchausen
syndrome by proxy, sexual abuses.), represents an important morbidity cause,
especially in the first years of the life. Nowadays, the battered child syndrome
includes forms of abuse and different degrees of negligence (moderate, serious
and light) in which the physical abuse could be absent. Determination of the
forms of abuse, their diagnosis, intervention and prevention, corresponds to
multidisciplinary teams, in which the pediatrician has a crucial role.
PMID- 11003965
TI - [Treatment of very low birth weight infant: is it evidenced-based?].
AB - AIM: To determine what percentage of therapeutic interventions for very low birth
weight infants undergoing neonatal intensive care is evidence based. METHODS: The
management of 80 very low birth weight infants admitted to our neonatal unit
during 1998 was retrospectively reviewed. For each clinical diagnosis e.g.
respiratory distress syndrome, patent ductus arteriosus or chronic lung disease
all interventions were recorder. Each intervention was then categorised according
to the level of supporting evidence. Level I was supported by evidence from
randomised controlled trials or meta-analysis of multiple trials. Level II
included interventions backed by convincing non-experimental evidence where
randomised controlled trials would be unnecessary or unethical. Level III were
treatments in common use without substantial supporting evidence. These
categorizations were made after extensive researching of Medline, The Cochrane
Database and the Randomised Controlled Trial Register, detailed hand-searching of
the literature as well as using local expertise and knowledge. RESULTS: 943
separate interventions were recorded in the charts of the 80 babies. Overall
91.3% were shown to be evidence-based of which 58.7% were level I, 32.6% were
level II and only 8.7% were level III. CONCLUSIONS: 91.3% of interventions for
very low birth weight infants in our neonatal intensive care unit were evidence
based and only 8.7% had no substantial supporting evidence. Care of the very low
birthweight infants is largely evidence-based.
PMID- 11003966
TI - [Hereditary spherocytosis in neonates. Review of our caseload].
AB - AIM: Review of hereditary spherocytosis diagnosed in infants younger than two
months and their follow up. PATIENTS AND METHODS: Retrospective study of 18
infants younger than two months diagnosed from 1973 to 1995. RESULTS: Diagnosis
was established in the first week of life in 50% of the patients. Hereditary
pattern was autosomic dominant in 94% of the cases. Anaemia was observed in all
the patients and hyperbilirubinemia in only 44%, although the latter was the
clinical presentation in patients diagnosed at younger age. Exchange transfusion
was performed in 3 children (1 with the severe form and 2 with the typical form
of the disease). During the first 6 months of age, 55% of infants presented
hemolytic crises that required transfusion in 91% of them. Both periodicity of
crises and transfusions decreased to 38 and 44% respectively after the first
year. Splenectomy was performed in the 3 children with severe forms and in 6 with
typical forms (mean age 8 years and 3 months). No cholecystectomy was required so
far. CONCLUSIONS: The authors believe that neonatal spherocytosis does not
implicate worse prognosis at follow up. Blood support is higher during the first
year of life. Elective splenectomy depends on age and transfusional requirements.
PMID- 11003967
TI - [Neurocutaneous melanosis].
AB - Neurocutaneous melanosis (NCM) is a rare congenital syndrome characterized by
large or multiple congenital melanocytic nevi and excessive proliferation of
melanotic cells in the leptomeninges. We report the case of a girl with a giant
hairy nevus and numerous small nevi since birth. Within the first 2 years of life
she developed clinical features of increased intracranial pressure and West s
syndrome. At 2 years of age she presented a right facial palsy and myelopathy.
Brain and spinal magnetic resonance imaging demonstrated meningeal infiltration.
Diagnosis of NCM was established by a detailed cytologic analyses of the
cerebrospinal fluid that revealed melanocytic cells. She received palliative
treatment. The girl died 2 months after. Patients with large or multiple
congenital melanocytic nevi should be carefully followed up with clinical
examination and neuroimaging to detect NCM. At present there is no curative
treatment. The association of NCM and West s syndrome has not been previously
described.
PMID- 11003968
TI - [Invasive disease caused by Streptococcus pyogenes. Report of a case with
cutaneous and kidney metastasis].
AB - Few cases of invasive disease due to Streptococcus pyogenes in children have been
described. Greater knowledge of this disease is needed due to its increasing
incidence and seriousness. New serotypes have been discovered with greater
virulence due to exotoxin production and to the development of resistance to
phagocytosis. We present a case of invasive disease due to S. pyogenes with
bacteremia and cutaneous and kidney metastasis, in a non-immunodeficient child.
The case is of interest because kidney dissemination has not been described in
the literature and because evolution was satisfactory with endovenous beta
lactamica treatment during 15 days for only 48 hours. The importance of ruling
out multi-organ metastatic foci, including use of urine cultures to rule out
kidney involvement are highlighted. The epidemiological, pathogenic, clinical and
diagnostic aspects of this entity, as reported in recent literature, are
described.
PMID- 11003969
TI - [Recurrent bowel intussusception and celiac disease].
AB - We report a 1-year-old girl with acute abdominal pain. Clinical examination
revealed distended abdomen with increased intestinal peristalsis without other
pathologic signs. Ultrasound of the abdomen showed a small bowel intussusception.
Seven days later, after a new episode of sudden acute abdominal pain, ultrasound
revealed a new bowel intussusception. Ig A and Ig G antigliadin-antibodies were
elevated and intestinal biopsy revealed total villous atrophy. After being placed
on a gluten-free diet the girl was free of colicky complaints and on repeated
ultrasound there was no sign of intussusception. With recurrent intussusception,
celiac disease should be considered as a cause.
PMID- 11003970
TI - [Cervical mass. What is your diagnosis?].
PMID- 11003971
TI - In vitro effects of interleukin-10, prednisolone, and GM-CSF on the non-specific
immune function of human polymorphonuclear leucocytes and monocytes.
AB - A wide range of immune-modulating effects make IL-10 a potential therapeutic
option in the treatment of numerous diseases pathophysiological based on a
dysregulation of cytokine production. The background of this study was to
investigate, whether the beneficial effects of a therapeutic immunosuppression
with IL-10 may be countered by an increased risk for infections due to impaired
effector cell functions of unspecific immunity. We demonstrated the in vitro
effects of IL-10 on phagocytosis (P), intracellular killing (K), and chemotactic
activity (C) by human neutrophils (PMN) and monocytes (MON) using Candida
albicans as test strain and compared the results to the effects of prednisolone
and GM-CSF. IL-10 reduced significantly the intracellular killing rate of PMN
compared to untreated phagocytes (60 +/- 16% versus 68 +/- 13%, mean +/- SD, p =
0.0002). High dose IL-10 (100 ng/ml) had a stimulating effect on the percentage
of phagocytizing MON (70.2 +/- 12.7% vs. 66.9 +/- 14.2%, p = 0.0436), without
impairing intracellular killing. Prednisolone reduced significantly the Candida
uptake by MON (57 +/- 18.1% vs. 66. 9 +/- 14.2%, p = 0.0019). In contrast to
prednisolone, neither MON nor PMN chemotaxis was suppressed by IL-10. In
conclusion, IL-10 had only marginal immunosuppressive effects on the unspecific
immunity compared to prednisolone.
PMID- 11003972
TI - Acute effects of 200 ppm 1,1,1-trichloroethane on the human EEG.
AB - OBJECTIVES: Even low concentrations of organic solvents used at work may cause
acute effects on the human central nervous system. We investigated the acute
effects of 200 ppm 1,1,1-trichloroethane on the human EEG. METHODS: 12 healthy
subjects were exposed for 4 hours to 200 ppm and to 20 ppm (control) in an
exposure chamber in a cross-over design. EEG was recorded before (reference) and
at the end of each exposure with eyes closed and open and during the Color Word
Stress test. Spectral power was calculated by Fast Fourier transformation and
related to reference values (per cent of baseline). Subjective symptoms and
effects of blinding with 20 ppm 1, 1,1-trichloroethane were assessed by
questionnaire. RESULTS: Blinding was not effective because of the strong smell of
1,1, 1-trichloroethane. The score for tiredness increased slightly during and
after exposure to 200 ppm. In the closed eye condition, the median percentage of
spectral power increased at all electrodes of the delta -band, significantly at
temporo-occipital leads. In the theta-band, the percentage of the median spectral
power was elevated at most of the electrodes but the parietal and some temporal
ones. As to the alpha subset1-band, the percentage of the median spectral power
was lower at the temporo-parieto-occipital electrodes, yielding significance at T
subset4. In the alpha subset2-band, the percentage of the median spectral power
was lower at all electrodes, significantly at T subset4 and T subset5. The
percentage of the median spectral power of the temporo-parieto-occipital
electrodes of the beta subset1 -band was lower during exposure to 200 ppm. There
were no clear-cut changes in the beta subset2 -band, in the open eye condition
and during the Color Word Stress test. CONCLUSION: The changes in EEG and the
increased score for tiredness indicate a slight sedative effect of 200 ppm 1,1,1
trichloroethane.
PMID- 11003973
TI - Effect of a fixed valerian-Hop extract combination (Ze 91019) on sleep polygraphy
in patients with non-organic insomnia: a pilot study.
AB - A pilot study with a fixed extract combination Ze 91019 of valerian and hop was
conducted in 30 patients suffering from mild-moderate, non-organic insomnia. The
diagnosis was confirmed by polysomnographic standard examinations. The patients
were treated with 2 tablets in the evening. Each tablet contains 250 mg valerian
extract and 60 mg hop extract. A polysomnographic re-examination after 2 weeks of
treatment revealed declines in the sleep latency and the wake time. As a
consequence the sleep efficiency increased. Sleep stage 1 (S1) was reduced and
the slow wave sleep increased. In addition, the patients judged their being
refreshed in the morning by assigning a rating of 1 to 6. They reported an
improvement after 2 weeks of treatment. No adverse events were observed. Based on
these findings a pivotal study can be designed.
PMID- 11003974
TI - The therapeutic effect of theophylline in mild obstructive sleep Apnea/Hypopnea
syndrome: results of repeated measurements with portable recording devices at
home.
AB - Theophylline has been recommended in the literature as a therapeutic option in
mild OSAHS. In mild obstructive sleep apnea/hypopnea syndrome (OSAHS), night-to
night variability of parameters of sleep-disordered breathing has been determined
rarely, we therefore compared the results of serial measurements of sleep
apnea/hypopnea parameters under the effects of placebo and theophylline. To this
end, we measured the individual variability of the apnea-hypopnea index (AHI) for
seven consecutive nights using a portable sleep apnea recording device, in 14
subjects (2 women, 12 men, mean age +/- [standard deviation] 50 +/- 8 years),
treated with placebo or theophylline in a double blind, randomized crossover
fashion, whose polysomnographically measured AHI was 13 +/- 5 /hour. Under
theophylline treatment in comparison with placebo we observed a small but
significant decrease in mean (of seven days) AHI at home (9.2 +/- 7.7 to 6.7 +/-
6.1 /hour), which was independent of body position. The night-to-night
variability of AHI at home was high (9. 2 +/- 8.9 /hour; range: 0-31.4 /hour) and
proved to be independent of body position and alcohol consumption. - In mild
OSAHS, repeated measurements of sleep related breathing events should be
performed. Theophylline showed a small but clinically insignificant potencial to
reduce AHI.
PMID- 11003975
TI - Intensified physiotherapy improves fitness to fly in cystic fibrosis patients.
AB - OBJECTIVES: The life expectancy for patients with cystic fibrosis has risen
constantly within the last 10 years to an average age over 20 years in western
countries. However, most of these patients are partially respiratory
insufficient. Frequently their physicians must decide whether it is acceptable to
expose them to reduced air pressure on board of an aeroplane during long distance
flights or how their fitness to fly can be improved prior to their annual
vacation. We investigated the effect of intensified daily physiotherapy -carried
out during a four weeks stay on Gran Canaria, Spain- on lung-function parameters,
oxygen saturation and saliva neopterin as marker for ongoing inflammation in the
respiratory tract. METHODS: 10 out of 12 patients (age 19 34 years, mean 28.6
years) were investigated two weeks prior and two weeks after their trip to the
Canaries, Spain. Lung function on ground level and during flights to and from the
island, oxygen saturation and saliva-flow adjusted neopterin in saliva were
measured. RESULTS: Over the entire group vital capacity (VC) improved
significantly from 2.89 l (range 1.37 3.95) to 3.36 l (range 1.23 5.24).
Intrathoracic gas volume as a sign for pulmonary hyperinflation- declined
slightly from 3.79 l (range 2.06 6.17) to 3.48 l (range 2. 18 5.85). The oxygen
saturation increased from 89.5% (range 79 - 92%) during the flight to the
Canaries to 94% (range 82 - 96%) during the return flight. Saliva neopterin
dropped from 0.8 pmol/min. (range 0.2 6.8 pmol/min) to 0.6 ( range 0.1 2.6
pmol/min) pointing to diminished inflammation in the respiratory tract.
CONCLUSION: Our results indicate that fitness to fly can be improved by intense
physiotherapy as shown by improvement of vital capacity and oxygen saturation
during flight. The influence of an additional climate change on the improvement
of lung function in CF-patients needs further evaluation.
PMID- 11003976
TI - Schistosomiasis and travel medicine.
AB - The rise in off-track tourism and the spread of schistosomiasis in previously non
endemic areas results in an increasing number of imported schistosomiasis cases.
Detection of eggs in stool or urine and specific serology supports the
diagnosis, however eosinophilia in early infection is low. In travel groups with
a single index case all members of the group with similar risk behaviour should
be examined since more than 50% of group members with similar risk behaviour are
likely to be infected. Asymptomatic, atypical and late presentation of the
disease might delay diagnosis. Praziquantel is not effective against immature
worms, therefore treatment of returning travellers with single dose praziquantel
is effective when started not earlier than 2 months after infection. A
combination of praziquantel plus artemether is thought to be effective also in
early stages of infection. Vaccination trials in endemic areas are in progress
but a single vaccine for travellers covering all schistosoma species will not be
available in the near future. Advising the traveller to avoid risk behaviour like
wading, bathing and swimming in endemic fresh waters and about the risk of
acquiring schistosomiasis through surface or spray water during boat tours will
help to reduce imported schistosomiasis.
PMID- 11003977
TI - Changes in cellular proliferation rate of lymphocytes after long-distance flights
as a possible risk for patients with HIV-infection.
AB - OBJECTIVES: Several studies showed that long-distance flights can influence
cellular immunity. This might be due to a cortisol- and catecholamin- induced
change in immunity with an impairment of T-lymphocyte dependent cellular immunity
and an enhancement of B-lymphocyte dependent humoral immunity. Similar results
can be found in patients with HIV. It is also known that progress of this disease
and affection of T-helper-cells by the virus are induced by stimulation of the
immune system, a phenomenon that also occurs during long distance flights.
Therefore, a possible interaction between long-distance flights and the
progression of HIV-infection should be discussed. METHODS: Cell cultures of 22
subjects after long-distance flights with and without rapid time zone shifts and
of 16 patients with HIV (stage 2 3) were investigated. Mononuclear blood cells
were stimulated with different lectins in culture and proliferation was measured
by incorporation of bromodesoxyuridine. Moreover, all cultures were titrated with
chromate concentrations between 0 to 700 ng/ml to measure the tolerance of the
cells against chromate (VI) in vitro as a marker of the functional efficiency of
the cellular part of the immune system. Maximal proliferation rate and tolerance
against chromate were compared in both groups. RESULTS: After long distance
flights tolerance against chromate decreased significantly during the first 24 h
after flight. After 48 h levels were similar to those 1 week after flights. The
decrease was similar to the results found in the stage 2 group of HIV-patients,
but by far less to the decrease in stage 3 patients. Maximal proliferation rate
dropped significantly during the second day after arrival compared to 1-week
control values. CONCLUSION: Changes in the cellular immune system in healthy
subjects after long-distance flights have been similar to the results of patients
with stage 2 of HIV-infection. Mechanisms of changes in both groups are
comparable in influencing T-cell-induced immunity. This could point to an
additive effect on cellular immunity of HIV-patients by long distance-flights.
Rosen neopterin concentrations and increases of apoptotic T-cells in both groups
support this assumption. Therefore, further studies are urgently needed to
investigate the interactions between HIV-infection and long-distance flights.
PMID- 11003978
TI - Right ventricular systolic pressure load alters myocyte maturation in fetal
sheep.
AB - The effects of right ventricular (RV) systolic pressure (RVSP) load on fetal
myocyte size and maturation were studied. Pulmonary artery (PA) pressure was
increased by PA occlusion from mean 47.4 +/- 5.0 (+/-SD) to 71 +/- 13.6 mmHg (P <
0.0001) in eight RVSP-loaded near-term fetal sheep for 10 days. The maximal
pressure generated by the RV with acute PA occlusion increased after RVSP load:
78 +/- 7 to 101 +/- 15 mmHg (P < 0.005). RVSP-load hearts were heavier (44.7 +/-
8.4 g) than five nonloaded hearts (31.8 +/- 0.2 g; P < 0.03); heart-to-body
weight ratio (10.9 +/- 1.1 and 6.5 +/- 0.9 g/kg, respectively; P < 0.0001). RVSP
RV myocytes were longer (101.3 +/- 10.2 microm) than nonloaded RV myocytes (88.2
+/- 8.1 microm; P < 0. 02) and were more often binucleated (82 +/- 13%) than
nonloaded myocytes (63 +/- 7%; P < 0.02). RVSP-loaded myocytes had less
myofibrillar volume than did nonloaded hearts (44.1 +/- 4.4% and 56. 1 +/- 2.6%;
P < 0.002). We conclude that RV systolic load 1) leads to RV myocyte enlargement,
2) has minor effects on left ventricular myocyte size, and 3) stimulates
maturation (increased RV myocyte binucleation). Myocyte volume data suggest that
RV systolic loading stimulates both hyperplastic and hypertrophic growth.
PMID- 11003979
TI - NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated
skeletal muscle myotubes.
AB - Nuclear factor-kappaB (NF-kappaB) regulates the transcription of a variety of
genes involved in immune responses, cell growth, and cell death. However, the
role of NF-kappaB in muscle biology is poorly understood. We recently reported
that tumor necrosis factor-alpha (TNF-alpha) rapidly activates NF-kappaB in
differentiated skeletal muscle myotubes and that TNF-alpha acts directly on the
muscle cell to induce protein degradation. In the present study, we ask whether
NF-kappaB mediates the protein loss induced by TNF-alpha. We addressed this
problem by creating stable, transdominant negative muscle cell lines. C2C12
myoblasts were transfected with viral plasmid constructs that induce
overexpression of mutant I-kappaBalpha proteins that are insensitive to
degradation via the ubiquitin-proteasome pathway. These mutant proteins
selectively inhibit NF-kappaB activation. We found that differentiated myotubes
transfected with the empty viral vector (controls) underwent a drop in total
protein content and in fast-type myosin heavy-chain content during 72 h of
exposure to TNF-alpha. In contrast, total protein and fast-type myosin heavy
chain levels were unaltered by TNF-alpha in the transdominant negative cell
lines. TNF-alpha did not induce apoptosis in any cell line, as assessed by DNA
ladder and annexin V assays. These data indicate that NF-kappaB is an essential
mediator of TNF-alpha-induced catabolism in differentiated muscle cells.
PMID- 11003980
TI - Blunted arterial baroreflex causes "pathological" heart rate turbulence.
AB - Sudden cardiac death is the leading cause of cardiovascular mortality in
developed countries. Recently, two post-myocardial-infarction risk predictors
were introduced that are superior to all other presently available indicators:
turbulence onset (TO) and turbulence slope (TS). These parameters characterize
the behavior of instantaneous heart rate after a ventricular premature beat,
i.e., they describe the reestablishing of heart rate control after an acute
perturbation. We propose that the dysfunction of an important cardiovascular
control mechanism, the arterial baroreflex, is the mechanism behind these new
potent markers. The hypothesis is tested by means of a physiological model
involving the excitation generation in the heart, the hemodynamic situation in
the aorta, and baroreceptor feedback mechanisms. The data show that a blunted
baroreceptor response of the heart resembles patterns of heart rate turbulence
that correspond to pathological values of TO and TS. The results of the model
suggest that the recently established risk parameters TO and TS characterize
baroreflex function, a known risk stratifier in patients.
PMID- 11003981
TI - Hematological changes and athletic performance in horses in response to high
altitude (3,800 m).
AB - This study had two goals: 1) measure hematologic changes with high-altitude
acclimatization in horses; and 2) assess the effect of 9 days at high altitude on
subsequent athletic performance at low altitude. Six horses performed
standardized exercise tests on a dirt track (before and during time at altitude)
and treadmill (pre- and postaltitude exposure). Resting and immediate
postexercise blood samples were measured for blood volume, lactate, red cell
number, packed cell volume, and 2,3-diphosphoglycerate (DPG) concentrations at
225 m, over a 9-day period at 3,800 m, and shortly after returning to 225 m.
Acclimatization produced increases in total red cell volume (38.2 +/- 2.4 to 48.1
+/- 2.9 ml/kg, P = 0.004) and DPG/hemoglobin concentrations (19.4 +/- 1.7
increased to 29.4 +/- 0. 4 micromol/g, P = 0.004). Two performance variables,
heart rate recovery postexercise and lactate recovery, were faster after
acclimatization.
PMID- 11003982
TI - Testicular development in Siberian hamsters depends on frequency and pattern of
melatonin signals.
AB - We investigated the impact of frequency and pattern of melatonin signals on
reproductive development in Siberian hamsters. Juvenile males gestated in short
day lengths and housed in constant illumination to suppress melatonin secretion
were infused with melatonin for 5 h either once or twice per day for 20 days.
Melatonin infusions at either frequency produced equivalent increases in testes
and body weights that exceeded those of animals infused with saline but were
indistinguishable from those of hamsters transferred to long day lengths. The
reproductive system appears to be maximally stimulated by a single short
melatonin signal each day. Other animals kept from birth in a short photoperiod
were treated 6 h after onset of darkness with the beta-adrenergic receptor
antagonist DL-propranolol to shorten melatonin secretion on the night of
injection but not on subsequent nights. This permitted interpolation of short
nightly melatonin signals of 4-5 h duration against a background of long
melatonin signals of 10-12 h duration on other nights. Treatment regimes that
maintained a 1:1 ratio of short to long melatonin signals for 8 wk stimulated
reproductive development; a 1:2 signal ratio, in each of three different
patterns, was uniformly ineffective. The number of successive short melatonin
signals had little influence on the interval across which successive melatonin
signals were summated to influence photoperiodic traits. The neuroendocrine axis
appears more responsive to short melatonin signal frequency than pattern for
development of the summer phenotype.
PMID- 11003983
TI - Panting in reindeer (Rangifer tarandus).
AB - Two winter-insulated Norwegian reindeer (Rangifer tarandus tarandus) were exposed
to air temperatures of 10, 20, 30, and 38 degrees C while standing at rest in a
climatic chamber. The direction of airflow through nose and mouth, and the total
and the nasal minute volumes, respectively, were determined during both closed-
and open-mouth panting. The animals alternated between closed- and open-mouth
panting, but the proportion of open-mouth panting increased with increasing heat
load. The shifts from closed- to open-mouth panting were abrupt and always
associated with a rise in respiratory frequency and respiratory minute volume.
During open-mouth panting, the direction of airflow was bidirectional in both
nose and mouth, but only 2.4 +/- (SD) 1.1% of the air was routed through the
nose. Estimates suggest that the potential for selective brain cooling is
markedly reduced during open-mouth panting in reindeer as a consequence of this
airflow pattern.
PMID- 11003984
TI - Red blood cell life span in the ovine fetus.
AB - Red cell life span within the fetal circulation has not been reported, although
erythrocyte life span has been studied in the adult and newborn. The present
study quantified red cell life span in 12 chronically catheterized fetal sheep at
97-136 days gestation (term = 150 days) with the use of autologous red cells
labeled with [(14)C]cyanate. Cyanate forms a permanent covalent bond with
hemoglobin and acts as a permanent red cell label. In the fetuses, blood (14)C
activity decreased in a curvilinear fashion with time and reached 50% of the
initial activity at 16.4 +/- 1.6 (SE) days. In contrast, (14)C activity of
autologous red cells in two adult ewes decreased linearly with time as expected,
reached 50% of the initial (14)C activity in 59 days, and yielded life spans of
117 and 121 days. Computer modeling and parameter optimization taking into
account growth and skewed life span distribution were used to analyze the (14)C
disappearance curve in each fetus. The mean life span of all red cells in the
fetal circulation was 63.6 +/- 5.8 days. Mean red cell life span increased
linearly from 35 to 107 days as fetal age increased from 97 to 136 days (r =
0.83, P < 0.001). Life span of cells produced at the time of labeling was
significantly greater than the mean life span. Fetal growth rate estimated from
parameter optimization was 3.28 +/- 0.72%/day; this compared well with the rate
of 3.40 +/- 0.14%/day calculated from fetal weights at autopsy. Mean corpuscular
volume decreased as a function of gestational age, but the decrease was small
compared with the large increase in red cell life span. We conclude the
following: 1) red cell life span in the fetal circulation is short compared with
the adult; 2) red cells in younger fetuses have shorter life spans than in near
term fetuses; 3) the curvilinear disappearance of labeled red cells in the fetus
appears to be due primarily to an expanding blood volume with fetal growth; and
4) red blood cell life span in a growing organism will be significantly
underestimated unless the expansion of blood volume with growth is taken into
account.
PMID- 11003985
TI - Metabolic depression and enhanced O(2) affinity of mitochondria in hypoxic
hypometabolism.
AB - This study examined whether the steady-state hypometabolism seen in overwintering
frogs (Rana temporaria) is reflected at the mitochondrial level either by a
reduction in their resting (state 4) and active (state 3) respiration rates
and/or by increases in O(2) affinity. We isolated mitochondria from the skeletal
muscle of cold-submerged frogs at different stages during their hibernation in
normoxic and hypoxic water. A modest metabolic depression at the whole animal
level (normoxic submergence) was not associated with a reduction in mitochondrial
state 4 and state 3 respiration rates. However, mitochondria isolated from frogs
that were submerged for 1 mo manifested an increase in their O(2) affinity
compared with controls and with animals submerged for 4 mo. Hypometabolism was
more pronounced at the whole animal level during hypoxic submergence and was
accompanied by 1) a reduction in mitochondrial state 4 and state 3 rates and 2)
an increase in the O(2) affinity of mitochondria. These findings demonstrate that
metabolic depression can be reflected at all levels of biological organization in
hypoxia-tolerant animals.
PMID- 11003986
TI - Substance P in the nucleus of the solitary tract augments bronchopulmonary C
fiber reflex output.
AB - Bronchopulmonary C fibers defend the lungs against injury from inhaled agents by
a central nervous system reflex consisting of apnea, cough, bronchoconstriction,
hypotension, and bradycardia. Glutamate is the putative neurotransmitter at the
first central synapses in the nucleus of the solitary tract (NTS), but substance
P, also released in the NTS, may modulate the transmission. To test the
hypothesis that substance P in the NTS augments bronchopulmonary C fiber input
and hence reflex output, we stimulated the C fibers with left atrial capsaicin
(LA CAP) injections and compared the changes in phrenic nerve discharge, tracheal
pressure (TP), arterial blood pressure (ABP), and heart rate (HR) in guinea pigs
before and after substance P injections (200 microM, 25 nl) in the NTS. Substance
P significantly augmented LA CAP-evoked increases in expiratory time by 10-fold
and increases in TP and decreases in ABP and HR by threefold, effects prevented
by neurokinin-1 (NK1) receptor antagonism. Thus substance P acting at NTS NK1
receptors can exaggerate bronchopulmonary C fiber reflex output. Because
substance P synthesis in vagal airway C fibers may be enhanced in pathological
conditions such as allergic asthma, the findings may help explain some of the
associated respiratory symptoms including cough and bronchoconstriction.
PMID- 11003987
TI - Intraportal glucose infusion and pancreatic islet blood flow in anesthetized
rats.
AB - The aim of the study was to evaluate whether a selective increase in portal vein
blood glucose concentration can affect pancreatic islet blood flow. Anesthetized
rats were infused (0.1 ml/min for 3 min) directly into the portal vein with
saline, glucose, or 3-O-methylglucose. The infused dose of glucose (1 mg. kg body
wt(-1). min(-1)) was chosen so that the systemic blood glucose concentration was
unaffected. Intraportal infusion of D-glucose increased insulin release and islet
blood flow; the osmotic control substance 3-O-methylglucose had no such effect. A
bilateral vagotomy performed 20 min before the infusions potentiated the islet
blood flow response and also induced an increase in whole pancreatic blood flow,
whereas the insulin response was abolished. Administration of atropine to
vagotomized animals did not change the blood flow responses to intraportal
glucose infusions. When the vagotomy was combined with a denervation of the
hepatic artery, there was no stimulation of islet blood flow or insulin release
after intraportal glucose infusion. We conclude that a selective increase in
portal vein blood glucose concentration may participate in the islet blood flow
increase in response to hyperglycemia. This effect is probably mediated via
periarterial nerves and not through the vagus nerve. Furthermore, this blood flow
increase can be dissociated from changes in insulin release.
PMID- 11003988
TI - GABAergic contribution to rat bladder hyperactivity after middle cerebral artery
occlusion.
AB - To evaluate the influences of gamma-aminobutyric acid (GABA) mechanisms on
bladder hyperactivity after left middle cerebral artery occlusion, cystometric
recordings were obtained from unanesthetized female rats. Intracerebroventricular
administration of both muscimol (GABA(A) receptor agonist; 0.1-10 nmol) and
baclofen (GABA(B) receptor agonist; 0.1-3 nmol) produced dose-dependent
inhibitions of micturition with increases in bladder capacity (BC). The effects
of high doses (1-10 nmol) were similar in sham-operated (SO) and cerebral
infarcted (CI) rats. However, lower doses of muscimol (0.1 or 0.3 nmol) and
baclofen (0.1 nmol) reduced BC in CI rats. After bicuculline (GABA(A) receptor
antagonist; 1 or 3 nmol) administration, BC in both SO and CI rats first
decreased and subsequently increased. An increase in urethral pressure was
observed after administration of bicuculline (3 nmol) but not with either
muscimol or baclofen. Infarct volumes in muscimol-, bicuculline-, or baclofen
treated rats were not significantly different from those of vehicle-treated rats.
These results suggest that GABAergic mechanisms inhibit the micturition reflex at
the supraspinal level but that this can change as a result of CI.
PMID- 11003989
TI - Gene expression in the rat supraoptic nucleus induced by chronic hyperosmolality
versus hyposmolality.
AB - Magnocellular neurons of the hypothalamo-neurohypophysial system play a
fundamental role in the maintenance of body homeostasis by secreting vasopressin
and oxytocin in response to systemic osmotic perturbations. During chronic
hyperosmolality, vasopressin and oxytocin mRNA levels increase twofold, whereas,
during chronic hyposmolality, these mRNA levels decrease to 10-20% of that of
normoosmolar control animals. To determine what other genes respond to these
osmotic perturbations, we have analyzed gene expression during chronic hyper-
versus hyponatremia. Thirty-seven cDNA clones were isolated by differentially
screening cDNA libraries that were generated from supraoptic nucleus tissue
punches from hyper- or hyponatremic rats. Further analysis of 12 of these cDNAs
by in situ hybridization histochemistry confirmed that they are osmotically
regulated. These cDNAs represent a variety of functional classes and include
cytochrome oxidase, tubulin, Na(+)-K(+)-ATPase, spectrin, PEP-19, calmodulin,
GTPase, DnaJ-like, clathrin-associated, synaptic glycoprotein, regulator of
GTPase stimulation, and gene for oligodendrocyte lineage-myelin basic proteins.
This analysis therefore suggests that adaptation to chronic osmotic stress
results in global changes in gene expression in the magnocellular neurons of the
supraoptic nucleus.
PMID- 11003990
TI - Mobilization of NK cells by exercise: downmodulation of adhesion molecules on NK
cells by catecholamines.
AB - The change of plasma catecholamine concentration correlates with the change of
natural killer (NK) activity and NK cell number in peripheral blood mononuclear
cells (PBMC) during and after moderate exercise. We studied the causal relation
between exercise-induced catecholamine and expression of adhesion molecules on NK
cells during and after exercise. The expression of CD44 and CD18 on CD3(-)CD56(+)
NK cells was significantly reduced during exercise (P < 0.01). When PBMC were
stimulated with 10(-8)M norepinephrine in vitro, the expression of these adhesion
molecules on CD3(-)CD56(+) NK cells was downmodulated within 30 min. The binding
capacity of NK cells to a CD44 ligand, hyaluronate, was reduced by the
stimulation with norepinephrine (P < 0.01). The intravenous injection of
norepinephrine in mice decreased the expression of CD44 and CD18 on CD3(
)NK1.1(+) cells (P < 0.01) and increased the number of CD3(-)NK1.1(+) cells in
PBMC (P < 0.01). These findings suggest that exercise-induced catecholamines
modulate the expression of adhesion molecules on NK cells, resulting in the
mobilization of NK cells into the circulation.
PMID- 11003991
TI - Norepinephrine reuptake, baroreflex dynamics, and arterial pressure variability
in rats.
AB - This study examined the effect of norepinephrine reuptake blockade with
desipramine (DMI) on the spontaneous variability of the simultaneously recorded
arterial pressure (AP) and renal sympathetic nerve activity (SNA) in conscious
rats. Acute DMI administration (2 mg/kg iv) depressed AP Mayer waves (
approximately 0.4 Hz) and increased low-frequency (<0.2 Hz) components of AP
variability. DMI decreased renal SNA variability, especially due to the abolition
of oscillations related to Mayer waves. To examine whether DMI-induced changes in
AP and renal SNA variabilities could be explained by alterations in the dynamic
characteristics of the baroreceptor reflex loop, the frequency responses of mean
AP to aortic depressor nerve stimulation were studied in urethan-anesthetized
rats. DMI accentuated the low-pass filter properties of the transfer function
without significantly altering the fixed time delay. The frequency responses of
iliac vascular conductance to stimulation of the lumbar sympathetic chain were
studied in an additional group of anesthetized rats. DMI did not markedly alter
the low-pass filter properties of the transfer function and slightly increased
the fixed time delay. These results suggest that the DMI-induced decrease in the
dynamic gain of the baroreceptor reflex is responsible for the decreased
spontaneous renal SNA variability and the accompanying increased AP variability.
The "slowing down" of baroreflex responses cannot be attributed to an effect of
DMI at the vascular neuroeffector junction.
PMID- 11003992
TI - Renal blood flow, early distal sodium, and plasma renin concentrations during
osmotic diuresis.
AB - Inconsistencies in previous reports regarding changes in early distal NaCl
concentration (ED(NaCl)) and renin secretion during osmotic diuresis motivated
our reinvestigation. After intravenous infusion of 10% mannitol, ED(NaCl) fell
from 42.6 to 34.2 mM. Proximal tubular pressure increased by 12.6 mmHg. Urine
flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin
concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration
rate decreased, however end-proximal flow remained unchanged. After a similar
volume of hypotonic glucose (152 mM), ED(NaCl) increased by 3.6 mM, (P < 0.01)
without changes in renal hemodynamics, urine flow, sodium excretion rate, or PRC.
Infusion of 300 micromol NaCl in a smaller volume caused ED(NaCl) to increase by
6.4 mM without significant changes in PRC. Urine flow and sodium excretion
increased significantly. There was a significant inverse relationship between
superficial nephron ED(NaCl) and PRC. We conclude that ED(Na) decreases during
osmotic diuresis, suggesting that the increase in PRC was mediated by the macula
densa. The results suggest that the natriuresis during osmotic diuresis is a
result of impaired sodium reabsorption in distal tubules and collecting ducts.
PMID- 11003993
TI - Dissociation of leptin secretion and adiposity during prehibernatory fattening in
little brown bats.
AB - Hibernating animals deposit adipose tissue before hibernation to withstand long
periods of reduced energy intake. Normally, adiposity is positively correlated
with increased secretion from adipose tissue of the satiety hormone, leptin.
During the prehibernatory phase of the little brown bat, Myotis lucifugus, body
mass and adiposity increased to a maximum within 12 days. Leptin secretion from
adipose tissue in vitro and plasma leptin, however, increased before the increase
in adiposity, then significantly decreased when adiposity increased. Basal
metabolic rate (BMR) decreased when plasma leptin was increasing. This was
followed by an increase in nonshivering thermogenic capacity and brown adipose
tissue mass. We conclude that in the early prehibernatory phase, BMR decreases
despite increasing plasma leptin levels, suggesting a state of relative leptin
resistance at that time. At later stages, adiposity increases as BMR continues to
decrease, and plasma leptin becomes dissociated from adiposity. Thus, in M.
lucifugus, hibernation may be achieved partly by removing the metabolic signal of
leptin during the fattening period of prehibernation.
PMID- 11003994
TI - Vascular reactivity and baroreflex function during hyperthermia in conscious
rats.
AB - The hemodynamic responses to vasoconstrictor agents are blunted during heating in
anesthetized rats. It is unknown whether reflex neural responses to these agents
are also altered during hyperthermia. Therefore, the purpose of this study was to
determine the effect of hyperthermia on the hemodynamic and baroreflex-mediated
sympathetic neural responses to vasoactive agents in conscious, unrestrained
rats. The splanchnic sympathetic nerve activity (SpNA) and systemic and regional
hemodynamic responses to injections of phenylephrine and sodium nitroprusside
were measured during normothermia (37 degrees C) and hyperthermia (41.5 degrees
C). The hemodynamic responses to phenylephrine and sodium nitroprusside were
blunted with heating, whereas the SpNA responses to both agents were augmented or
unchanged. At 41.5 degrees C, the baroreflex curves relating heart rate (HR) and
SpNA to mean arterial blood pressure were shifted to the right. The operating
range and gain of the blood pressure (BP)-HR reflex were significantly reduced
during heating, whereas the operating range of the BP-SpNA reflex was augmented
at 41.5 degrees C. These results indicate that heating alters the cardiovascular
and sympathetic neural responses to vasoactive agents in vivo. Furthermore, the
data suggest that heating differentially affects arterial baroreflex control of
HR and SpNA, shifting both curves toward higher BP values but selectively
attenuating baroreflex control of HR.
PMID- 11003995
TI - Angiotensin II infusion to the midgestation ovine fetus: effects on the fetal
kidney.
AB - Renal and cardiovascular responses to an intravenous infusion of ANG II (1
microg/h) or saline for 3 days were examined in ovine fetuses at midgestation (75
85 days of gestation, term 150 days). ANG II caused an increase in fetal blood
pressure (36 +/- 2 to 44 +/- 3 mmHg) and urine flow rate (8 +/- 2 to a maximum of
18 +/- 6 ml/h). Plasma renin concentrations decreased in ANG II-infused fetuses.
Fetal fluids (amniotic and allantoic) did not differ in volume or composition
between the groups when measured at postmortem. There was no difference in the
expression levels of the mRNA for the angiotensin (AT(1) or AT(2)) receptors
between the two groups when measured by an RNase protection assay. However, there
was a significant decline in renin and AT(1) receptor gene expression when
measured by a real-time polymerase chain reaction method. These results indicate
that ANG II is diuretic and pressor when infused at midgestation. ANG II can
feedback to decrease renin secretion by the fetal kidney, and this may occur by
decreased renin gene expression.
PMID- 11003996
TI - Impact of gender and endothelin on renal vasodilation and hyperfiltration induced
by relaxin in conscious rats.
AB - Chronic administration of the hormone relaxin elicits renal vasodilation that is
dependent on nitric oxide (NO) in both conscious intact and ovariectomized female
rats. Our first objective was to test whether the hormone, when administered to
approximate serum concentrations found in midterm pregnant rats, induces renal
vasodilation in males. Glomerular filtration rate (GFR) and effective renal
plasma flow (ERPF) increased significantly, on average, by 33 and 49% over
baseline, respectively, after 5 days of recombinant human relaxin (rhRLX)
administration to 12 conscious male rats by subcutaneous osmotic minipump. There
were also significant decreases in hematocrit, plasma osmolality, and sodium
concentration. Another objective was to determine whether endogenous endothelin
(ET; via the endothelial ET(B) receptor) mediates the NO-dependent renal
vasodilation produced by relaxin. rhRLX or vehicle was administered to conscious
female rats (n = 9 and 8 rats, respectively). On the fifth day, baseline GFR and
ERPF were both increased, on average, by 20-30% in the rats administered rhRLX (P
< 0.05 vs. vehicle). Next, the specific ET(B)-receptor antagonist RES-701-1 was
infused intravenously over 4 h in both groups of rats. In response to RES-701-1,
there was a significant decline in both GFR and ERPF in the rats receiving rhRLX
such that renal function converged in the two groups of animals. We conclude 1)
relaxin induces marked changes in the renal circulation and in osmoregulation
regardless of gender and 2) relaxin-induced renal vasodilation and
hyperfiltration are mediated by endothelin through the endothelial ET(B) receptor
subtype and NO.
PMID- 11003997
TI - Impaired response of UCP family to cold exposure in diabetic (db/db) mice.
AB - Impaired activity of the uncoupling protein (UCP) family has been proposed to
promote obesity development. The present study examined differences in UCP
responses to cold exposure between leptin-resistance obese (db/db) mice and their
lean (C57Ksj) littermates. Basal UCP1 and UCP3 mRNA expression in brown adipose
tissue was lower in obese mice compared with lean mice, but UCP2 expression in
white adipose tissue (WAT) was higher. Basal skeletal muscle UCP3 did not change
remarkably. The UCP family mRNAs, which were upregulated 12 and 24 h after cold
exposure (4 degrees C), were returned to prior levels 12 h after rewarming
exposure (21 degrees C) in lean mice. The accelerating effects of cold exposure
on the UCP family were impaired in db/db obese mice. Together with these changes,
WAT lipoprotein lipase mRNA was downregulated, and the concentration of serum
free fatty acid was increased in response to cold exposure in the lean mice but
not in db/db obese littermates. The impaired function of the UCP family and
diminished lipolysis in response to cold exposure indicate that the reduced
lipolytic activity may contribute to the inactivation of the UCP family in db/db
obese mice.
PMID- 11003998
TI - Conditioned suppression of contact sensitivity is independent of sympathetic
splenic innervation.
AB - The present study investigated the role of sympathetic innervation of the spleen
in conditioned suppression of a contact hypersensitivity (CHS) reaction.
Behavioral conditioning was achieved by pairing saccharin drinking solution
(conditioned stimulus, CS) with injection of cyclosporin A (CsA, 20 mg/kg;
unconditioned stimulus, UCS). Four days after sensitization of the animals by
application of a 5% 2,4-dinitrochlorobenzene (DNCB) to abdominal skin, the
animals were challenged by applying a 1% DNCB solution to the ear. The CHS
response was monitored by measuring the degree of ear swelling. Saccharin re
presentation reduced ear swelling to a magnitude that approached that achieved by
CsA treatment. Histological examination demonstrated that the conditioned
reduction of ear swelling was produced by a reduced leukocyte infiltration of the
ear. Prior sympathetic denervation of the spleen did not alter the conditioned
suppression of the CHS response. These data indicate that behavioral conditioning
using CsA produces alterations of CHS that, unlike conditioned prolongation of
heart allograft survival, are independent of sympathetically regulated
conditioned alterations in the spleen.
PMID- 11003999
TI - Circadian rhythm changes in core temperature over the menstrual cycle: method for
noninvasive monitoring.
AB - The purpose of this study was to determine whether core temperature (T(c))
telemetry could be used in ambulatory women to track changes in the circadian
T(c) rhythm during different phases of the menstrual cycle and, more
specifically, to detect impending ovulation. T(c) was measured in four women who
ingested a series of disposable temperature sensors. Data were collected each
minute for 2-7 days and analyzed in 36-h segments by automated cosinor analysis
to determine the mesor (mean temperature), amplitude, period, acrophase (time of
peak temperature), and predicted circadian minimum core temperature (T(c-min))
for each cycle. The T(c) mesor was higher (P < or = 0.001) in the luteal (L)
phase (37.39 +/-0.13 degrees C) and lower in the preovulatory (P) phase (36.91 +/
0.11 degrees C) compared with the follicular (F) phase (37.08 +/-0.13 degrees C).
The predicted T(c-min) was also greater in L (37.06 +/- 0.14 degrees C) than in
menses (M; 36.69 +/- 0.13 degrees C), F (36. 6 +/- 0.16 degrees C), and P (36.38
+/- 0.08 degrees C) (P < or = 0. 0001). During P, the predicted T(c-min) was
significantly decreased compared with M and F (P < or = 0.0001). The amplitude of
the T(c) rhythm was significantly reduced in L compared with all other phases (P
< or = 0.005). Neither the period nor acrophase was affected by menstrual cycle
phase in ambulatory subjects. The use of an ingestible temperature sensor in
conjunction with fast and accurate cosinor analysis provides a noninvasive method
to mark menstrual phases, including the critical preovulatory period.
PMID- 11004000
TI - Treadmill running produces both positive and negative physiological adaptations
in Sprague-Dawley rats.
AB - Exercise training produces a vast array of physiological adaptations, ranging
from changes in metabolism to muscle mitochondrial biogenesis. Researchers
studying the physiological effects of exercise often use animal models that
employ forced exercise regimens that include aversive motivation, which could
activate the stress response. This study examined the effect of forced treadmill
running (8 wk) on several physiological systems that are sensitive to training
and stress. Forced treadmill running produced both positive and negative
physiological adaptations. Indicative of positive training adaptations, exercised
male Sprague-Dawley rats had a decrease in body weight gain and an increase in
muscle citrate synthase activity compared with sedentary controls. In contrast,
treadmill running also resulted in the potentially negative adaptations of
adrenal hypertrophy, thymic involution, decreased serum corticosteroid binding
globulin, elevated lymphocyte nitrite concentrations, suppressed lymphocyte
proliferation, and suppressed antigen-specific IgM. Such alterations in
neuroendocrine tissues and immune responses are commonly associated with chronic
stress. Thus treadmill running produces both positive training adaptations and
potentially negative adaptations that are indicative of chronic stress.
Researchers employing forced activity need to be aware that this type of exercise
procedure also produces physiological adaptations indicative of chronic stress
and that these changes could potentially impact other measures of interest.
PMID- 11004001
TI - Effect of gender on vestibular sympathoexcitation.
AB - Studies have suggested that premenopausal women are more prone to orthostatic
intolerance than men. Additionally, it has been postulated that the
vestibulosympathetic reflex is important in regulating postural-related changes
in sympathetic activity. The purpose of the present study was to determine
whether men and women differ in their sympathetic and cardiovascular responses to
stimulation of the otolith organs elicited by head-down rotation (HDR). Heart
rate (HR), arterial pressure, calf blood flow (CBF), and leg muscle sympathetic
nerve activity (MSNA) were measured during 3 min of HDR in the prone posture in
33 women and 30 men. With the exception of HR (71 +/- 2 and 63 +/- 1 beats/min
for women and men, respectively; P < 0.01), all baseline variables were not
different between genders. There were no gender differences in responses to HDR.
MSNA increased 72 +/- 33 units (43%) in the men and 88 +/- 15 units (59%) in the
women during HDR (P < 0.01). CBF decreased [-0.6 +/- 0.1 (15%) and -0.5 +/- 0.1
(19%) ml. min(-1). 100 ml(-1)] and calf vascular resistance increased [8 +/- 2
(21%) and 11 +/- 3 (25%) units during HDR for men and women, respectively (P <
0.01)]. Both in the men and women, HR increased 2 +/- 1 beats/min (P < 0.01).
These results demonstrate that sympathetic activation during HDR in the prone
posture is similar in men and women. Therefore, these findings suggest that the
vestibulosympathetic reflex is not different between healthy men and women.
PMID- 11004002
TI - Comparison of the effects of sucrose and fructose on insulin action and glucose
tolerance.
AB - The purpose of the present study was to determine whether fructose is the
nutrient mediator of sucrose-induced insulin resistance and glucose intolerance.
Toward this end, male rats were fed a purified starch diet (68% of total
calories) for a 2-wk baseline period. After this, rats either remained on the
starch (ST) diet or were switched to a sucrose (SU, 68% of total calories),
fructose/glucose (F/G, 34/34% of total calories), or fructose/starch (F/ST,
34/34% of total calories) diet for 5 wk. Rats then underwent either an
intravenous glucose tolerance test (n = 10/diet) or a euglycemic,
hyperinsulinemic clamp (n = 8 or 9/diet). Incremental glucose and insulin areas
under the curve in SU, F/G, and F/ST were on average 61 and 29% greater than ST,
respectively, but not significantly different from one another. During clamps,
glucose infusion rates (mg. kg(-1). min(-1)) required to maintain euglycemia were
significantly lower (P < 0.05) in SU, F/G, and F/ST (13.4 +/- 0.9, 9. 5 +/- 1.7,
11.3 +/- 1.3, respectively) compared with ST (22.8 +/- 1. 1). Insulin suppression
of glucose appearance (mg. kg(-1). min(-1)) was significantly lower (P < 0.05) in
SU, F/G, and F/ST (5.6 +/- 0.5, 2.2 +/- 1.2, and 6.6 +/- 0.7, respectively)
compared with ST (9.6 +/- 0.4). Insulin-stimulated glucose disappearance (mg. kg(
1). min(-1)) was significantly lower (P < 0.05) in SU, F/G, and F/ST (17. 9 +/-
0.6, 16.2 +/- 1.3, 15.3 +/- 1.8, respectively) compared with ST (24.7 +/- 1.2).
These data suggest that fructose is the primary nutrient mediator of sucrose
induced insulin resistance and glucose intolerance.
PMID- 11004003
TI - Effect of neonatal hypoxia on the development of hepatic lipase in the rat.
AB - Increases in plasma lipids occur during hypoxia in suckling but not in weaned
rats and may result from altered hepatic enzyme activity. We exposed rats to 7
days of hypoxia from birth to 7 days of age (suckling) or from 28 to 35 days of
age (weaned at day 21). Hypoxia led to an increase in hepatic lipid content in
the suckling rat only. Hepatic lipase was decreased to approximately 45% of
control in 7-day-old rats exposed to hypoxia but not in hypoxic 35-day-old rats.
Hypoxic suckling rats also had a 50% reduction in lactate dehydrogenase activity,
whereas transaminase activity and CYP1A and CYP3A protein content were not
different between hypoxic and normoxic groups. Additional rats were studied 7 and
14 days after recovery from hypoxic exposure from birth to 7 days of age; hepatic
lipase activity had recovered to 85% by 7 days and to 100% by 14 days in the rats
previously exposed to hypoxia. Administration of dexamethasone to neonatal rats
to simulate the hyperglucocorticoid state found in hypoxic 7-day-old rats led to
a moderate decrease ( approximately 75% of control) in hepatic lipases.
Developmentally, in the normoxic state, hepatic lipases increased rapidly after
birth and reached levels more than twofold that of the newborn by 7 days of age.
Hypoxia delays the maturation of hepatic lipases. We suggest that the decrease in
hepatic lipase activity contributes to hyperlipemia in the hypoxic newborn rats.
PMID- 11004004
TI - Amygdala-lesion obesity: what is the role of the various amygdaloid nuclei?
AB - Anatomic descriptions of amygdaloid lesions resulting in hyperphagia and obesity
in rats, cats, and dogs have been inconsistent and often contradictory,
frequently resulting in failures to replicate. The present study attempted to
reconcile these differences by examining common areas of overlap among
differently placed lesions in female rats. Small bilateral lesions of the most
posterodorsal aspects of the amygdala resulted in substantial weight gains (mean
= 45.4 g/10 days). The smallest lesions caused damage limited to the
posterodorsal medial amygdaloid nucleus and the bed nucleus of the stria
terminalis and were directly in the area where axons are collecting to form the
stria terminalis. Larger lesions that extensively damaged the central and/or
anterodorsal medial amygdaloid nuclei sometimes resulted in excess weight gains,
as did very large lesions of the basolateral nuclei, but substantial weight gains
occurred only when the lesions extended (unilaterally or bilaterally) into the
posterodorsal amygdala. Examination of previously published brain sections
indicated that the hyperphagia and obesity that have been observed after widely
differing lesion placements in cats and dogs were also the result of damage to a
common area of overlap (i.e., the bed nucleus and/or stria terminalis). In rats,
the critical area producing weight gain has extensive reciprocal relations with
the medial hypothalamus.
PMID- 11004005
TI - Differential stress responsivity in diet-induced obese and resistant rats.
AB - The relationship between stress and obesity was assessed in male rats selectively
bred to develop either diet-induced obesity (DIO) or diet resistance (DR) when
fed a high-energy, 31% fat diet for 3 wk followed by 2 wk on a hyperphagic liquid
diet (Ensure). One-half of the rats of each phenotype were subjected to moderate
daily, unpredictable stress (cage changing, exposure to conspecific, swim, and
immobilization stress, intraperitoneal saline injection) during the 5 wk. Both
stressed and unstressed DIO rats were 26% heavier and ate 27% more than
comparable DR rats at onset and had 48% lower basal morning plasma corticosterone
levels. Stressed DR rats gained less weight and had significant elevations of
basal morning corticosterone but reduced basal sympathetic activity (24-h urine
norepinephrine) over 5 wk compared with their unstressed DR controls. Terminally,
there was a 35% increase in the paraventricular nucleus corticotropin-releasing
hormone mRNA expression. On the other hand, stressed DIO rats showed only a
transient early increase in open-field activity and a terminal increase in basal
corticosterone levels as the only effects of stress. Thus DIO rats are
hyporesponsive to chronic stress compared with DR rats. This is in keeping with
several other known differences in hypothalamopituitary and autonomic function in
this model.
PMID- 11004006
TI - Osteoblast tissue-nonspecific alkaline phosphatase antagonizes and regulates PC
1.
AB - Tissue-nonspecific alkaline phosphatase (TNAP) is essential for bone matrix
mineralization, but the central mechanism for TNAP action remains undefined. We
observed that ATP-dependent (45)Ca precipitation was decreased in calvarial
osteoblast matrix vesicle (MV) fractions from TNAP-/- mice, a model of infantile
hypophosphatasia. Because TNAP hydrolyzes the mineralization inhibitor inorganic
pyrophosphate (PP(i)), we assessed phosphodiesterase nucleotide pyrophosphatase
(PDNP/NTPPPH) activity, which hydrolyzes ATP to generate PP(i). Plasma cell
membrane glycoprotein-1 (PC-1), but not the isozyme B10 (also called PDNP3)
colocalized with TNAP in osteoblast MV fractions and pericellular matrix. PC-1
but not B10 increased MV fraction PP(i) and inhibited (45)Ca precipitation by
MVs. TNAP directly antagonized inhibition by PC-1 of MV-mediated (45)Ca
precipitation. Furthermore, the PP(i) content of MV fractions was greater in
cultured TNAP-/- than TNAP+/+ calvarial osteoblasts. Paradoxically, transfection
with wild-type TNAP significantly increased osteoblast MV fraction NTPPPH.
Specific activity of NTPPPH also was twofold greater in MV fractions of
osteoblasts from TNAP+/+ mice relative to TNAP-/- mice. Thus TNAP attenuates PC
1/NTPPPH-induced PP(i) generation that would otherwise inhibit MV-mediated
mineralization. TNAP also paradoxically regulates PC-1 expression and NTPPPH
activity in osteoblasts.
PMID- 11004007
TI - Circadian rhythms of body temperature and activity levels during 63 h of hypoxia
in the rat.
AB - The hypothermic response of rats to only brief ( approximately 2 h) hypoxia has
been described previously. The present study analyzes the hypothermic response in
rats, as well as level of activity (L(a)), to prolonged (63 h) hypoxia at rat
thermoneutral temperature (29 degrees C). Mini Mitter transmitters were implanted
in the abdomens of 10 adult Sprague-Dawley rats to continuously record body
temperature (T(b)) and L(a). After habituation for 7 days to 29 degrees C and
12:12-h dark-light cycles, 48 h of baseline data were acquired from six control
and four experimental rats. The mean T(b) for the group oscillated from a
nocturnal peak of 38.4 +/- 0.18 degrees C (SD) to a diurnal nadir of 36.7 +/-
0.15 degrees C. Then the experimental group was switched to 10% O(2) in N(2). The
immediate T(b) response, phase I, was a disappearance of circadian rhythm and a
fall in T(b) to 36.3 +/- 0.52 degrees C. In phase II, T(b) increased to a peak of
38.7 +/- 0.64 degrees C. In phase III, T(b) gradually decreased. At reoxygenation
at the end of the hypoxic period, phase IV, T(b) increased 1.1 +/- 0.25 degrees
C. Before hypoxia, L(a) decreased 70% from its nocturnal peak to its diurnal
nadir and was entrained with T(b). With hypoxia L(a) decreased in phase I to
essential quiescence by phase II. L(a) had returned, but only to a low level in
phase III, and was devoid of any circadian rhythm. L(a) resumed its circadian
rhythm on reoxygenation. We conclude that 63 h of sustained hypoxia 1) completely
disrupts the circadian rhythms of both T(b) and L(a) throughout the hypoxic
exposure, 2) the hypoxia-induced changes in T(b) and L(a) are independent of each
other and of the circadian clock, and 3) the T(b) response to hypoxia at
thermoneutrality has several phases and includes both hypothermic and
hyperthermic components.
PMID- 11004008
TI - Contribution of central ANG II to acute stress-induced changes in baroreflex
function in young rats.
AB - The aim of the present investigation was to characterize the baroreflex in weaned
23- to 25-day-old rats when maternal influences were no longer present. The
relationship between mean arterial pressure (MAP) and heart rate (HR) was
determined during baroreceptor loading with phenylephrine and baroreceptor
unloading with sodium nitroprusside in conscious rats, first in the freely moving
state and subsequently during acute stress. In unstressed rats, the slope of the
relationship between MAP and HR was greater during baroreceptor loading than
baroreceptor unloading. Acute stress significantly attenuated the slope of the
response to baroreceptor loading but increased the slope of the response to
baroreceptor unloading. Pretreatment with intracerebroventricular or intravenous
losartan, an AT(1) receptor antagonist, or intracerebroventricular alpha-helical
corticotropin-releasing hormone (alpha-hCRH), a receptor antagonist, before the
stress significantly reduced the stress-induced attenuation of slope during
baroreceptor loading. Hence, young postweaning rats can alter baroreflex function
during acute stress in a manner that would favor increases in MAP. Even at this
young age, a central action of ANG II and CRH contributes to these stress-induced
adaptations.
PMID- 11004009
TI - Does angiotensin II have a significant tonic action on cardiovascular neurons in
the rostral and caudal VLM?
AB - The peptidic ANG II receptor antagonists [Sar(1),Ile(8)]ANG II (sarile) or
[Sar(1),Thr(8)]ANG II (sarthran) are known to decrease arterial pressure and
sympathetic activity when injected into the rostral part of the ventrolateral
medulla (VLM). In anesthetized rabbits and rats, the profound depressor and
sympathoinhibitory response after bilateral microinjections of sarile or sarthran
into the rostral VLM was unchanged after prior selective blockade of angiotensin
type 1 (AT(1)) and ANG-(1---7) receptors, although this abolished the effects of
exogenous ANG II. Unlike the neuroinhibitory compounds muscimol or lignocaine,
microinjections of sarile in the rostral VLM did not affect respiratory activity.
Sarile or sarthran in the caudal VLM resulted in a large pressor and
sympathoexcitatory response, which was also unaffected by prior blockade of AT(1)
and ANG-(1---7) receptors. The results indicate that the peptidic ANG receptor
antagonists profoundly inhibit the tonic activity of cardiovascular but not
respiratory neurons in the VLM and that these effects are independent of ANG II
or ANG-(1---7) receptors.
PMID- 11004010
TI - Amiloride-sensitive signals and NaCl preference and appetite: a lick-rate
analysis.
AB - Rats prefer hypotonic and isotonic NaCl solutions to water in long-access
drinking paradigms. To focus on the role of taste signals in NaCl preference,
licking patterns of rats with 30-s exposure to NaCl solutions (0-0.5 M) were
examined when they were either water deprived, sodium depleted, or not deprived
(NaCl mixed in dilute sucrose). In all three conditions, rats displayed a
preference for NaCl. The addition of 100 microM amiloride, a sodium channel
blocker, to NaCl did not change rats' licking when they were sodium replete but
dramatically reduced licking when they were deplete. Transection of the chorda
tympani (CT) nerve, an afferent pathway for amiloride-sensitive Na(+) signals,
had no effect on NaCl preference in nondeprived rats and only a modest effect on
those that were Na(+) deplete. Amiloride was found to exert significant
suppression of NaCl intake in Na(+)-depleted rats with transection of the CT,
supporting the existence of other afferent pathways for transmission of amiloride
sensitive Na(+) signalling. Together, these studies argue for the involvement of
different neural signalling mechanisms in NaCl preference in the presence and
absence of explicit Na(+) need.
PMID- 11004011
TI - Detection of apical Na(+)/H(+) exchanger activity inhibition in proximal tubules
induced by acute hypertension.
AB - We previously showed that acute arterial hypertension induces an inhibition of
fluid and NaCl reabsorption in proximal tubules of Sprague-Dawley rats, which is
associated with a rapid reversible internalization of apical Na(+)/H(+) exchanger
in brush border. To determine whether there is a corresponding inhibition of
apical Na(+)/H(+) exchanger activity in proximal tubules to account for the
reduced tubular reabsorption, an instrument capable of measuring intracellular pH
(pH(i)) ratiometrically and repeatedly on the surface of kidney with high
temporal resolution is required. We report the design and validation of such a
fluorimetric system based on two ultraviolet nitrogen-pulsed lasers and a
photomultiplier. pH(i) of proximal tubules in situ was measured with pH-sensitive
fluorescence dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein at 5 Hz. Using
the initial rate of change of pH(i) (dpH(i)/dt) during luminal Na(+) removal as
an index of apical Na(+)/H(+) exchanger activity, the exchanger activity was
found to be reduced by 52 +/- 11% (n = 14, P < 0.05) compared with the baseline
after 20 min of induced acute hypertension. The inhibition of Na(+)/H(+) exchange
activity was alleviated when the blood pressure was returned to prehypertensive
level. These observations indicate that acute changes in arterial pressure can
reversibly inhibit apical Na(+)/H(+) exchanger activity, which might contribute
to pressure natriuresis in proximal tubule.
PMID- 11004012
TI - Dual role of PKC in modulating pharmacomechanical coupling in fetal and adult
cerebral arteries.
AB - This study tested the hypothesis that protein kinase C (PKC) has dual regulation
on norepinephrine (NE)-mediated inositol 1,4, 5-trisphosphate [Ins (1,4,5)P(3)]
pathway and vasoconstriction in cerebral arteries from near-term fetal (
approximately 140 gestational days) and adult sheep. Basal PKC activity values
(%membrane bound) in fetal and adult cerebral arteries were 38 +/- 4% and 32 +/-
4%, respectively. In vessels of both age groups, the PKC isoforms alpha, beta(I),
beta(II), and delta were relatively abundant. In contrast, compared with the
adult, cerebral arteries of the fetus had low levels of PKC-epsilon. In response
to 10(-4) M phorbol 12,13-dibutyrate (PDBu; PKC agonist), PKC activity in both
fetal and adult cerebral arteries increased 40-50%. After NE stimulation, PKC
activation with PDBu exerted negative feedback on Ins(1,4,5)P(3) and
intracellular Ca(2+) concentration ([Ca(2+)](i)) in arteries of both age groups.
In turn, PKC inhibition with staurosporine resulted in augmented NE-induced
Ins(1,4,5)P(3) and [Ca(2+)](i) responses in adult, but not fetal, cerebral
arteries. In adult tissues, PKC stimulation by PDBu increased vascular tone, but
not [Ca(2+)](i). In contrast, in the fetal artery, PKC stimulation was associated
with an increase in both tone and [Ca(2+)](i). In the presence of zero
extracellular [Ca(2+)], these PDBu-induced responses were absent in the fetal
vessel, whereas they remained unchanged in the adult. We conclude that, although
basal PKC activity was similar in fetal and adult cerebral arteries, PKC's role
in NE-mediated pharmacomechanical coupling differed significantly in the two age
groups. In both fetal and adult cerebral arteries, PKC modulation of NE-induced
signal transduction responses would appear to play a significant role in the
regulation of vascular tone. The mechanisms differ in the two age groups,
however, and this probably relates, in part, to the relative lack of PKC-epsilon
in fetal vessels.
PMID- 11004013
TI - Baroreflex modulation of peripheral vasoconstriction during progressive
hypothermia in anesthetized humans.
AB - Mild hypothermia is a major concomitant of surgery under general anesthesia. We
examined the hypothesis that baroreceptor loading/unloading modifies
thermoregulatory peripheral vasoconstriction and, consequently, body core
temperature in subjects undergoing lower abdominal surgery with general
anesthesia. Thirty-six patients were divided into four groups: control group (C),
applied positive end-expiratory pressure (PEEP; 10 cmH(2)O) group (P), applied
leg-up position group (L), and a group of leg-up position patients with PEEP
starting 90 min after induction of anesthesia (L + P). The esophageal temperature
(T(es)) and the forearm-fingertip temperature gradient, as an index of peripheral
vasoconstriction, were monitored for 3 h after induction of anesthesia. Mean
arterial pressure and pulse pressure did not change during the study in any
group. The change in right atrial transmural pressure from the baseline value was
0.3 +/- 0.1 mmHg in C, -3.0 +/- 0.5 mmHg in P, and 2.3 +/- 0.4 mmHg in L (P <
0.01). The change in T(es) at the end of the study was -1.7 +/- 0.1 (35.1 +/-
0.1) degrees C in C, -1.1 +/- 0.1 (35.7 +/- 0.1) degrees C in P, and -2.7 +/- 0.1
(34.1 +/- 0.1) degrees C in L, showing significant differences (P < 0.01). The
T(es) threshold for thermal peripheral vasoconstriction was 35.6 +/- 0.1 degrees
C in C, 36.2 +/- 0.2 degrees C in P, and 34.8 +/- 0.2 degrees C in L (P < 0.01).
Excessive T(es) decrease in the leg-up-position operation was attenuated by
applying PEEP (L + P group; P < 0.05). Our data indicate that baroreceptor
loading augments and unloading prevents perioperative hypothermia in anesthetized
and paralyzed subjects by reducing and increasing the body temperature threshold
for peripheral vasoconstriction, respectively.
PMID- 11004014
TI - Baroreflexes prevent neurally induced sodium retention in angiotensin
hypertension.
AB - Recent studies indicate that renal sympathetic nerve activity is chronically
suppressed during ANG II hypertension. To determine whether cardiopulmonary
reflexes and/or arterial baroreflexes mediate this chronic renal
sympathoinhibition, experiments were conducted in conscious dogs subjected to
unilateral renal denervation and surgical division of the urinary bladder into
hemibladders to allow separate 24-h urine collection from denervated (Den) and
innervated (Inn) kidneys. Dogs were studied 1) intact, 2) after thoracic vagal
stripping to eliminate afferents from cardiopulmonary and aortic receptors
[cardiopulmonary denervation (CPD)], and 3) after subsequent denervation of the
carotid sinuses to achieve CPD plus complete sinoaortic denervation (CPD + SAD).
After control measurements, ANG II was infused for 5 days at a rate of 5 ng. kg(
1). min(-1). In the intact state, 24-h control values for mean arterial pressure
(MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys
(Den/Inn) were 98 +/- 4 mmHg and 1.04 +/- 0.04, respectively. ANG II caused
sodium retention and a sustained increase in MAP of 30-35 mmHg. Throughout ANG II
infusion, there was a greater rate of sodium excretion from Inn vs. Den kidneys
(day 5 Den/Inn sodium = 0.51 +/- 0.05), indicating chronic suppression of renal
sympathetic nerve activity. CPD and CPD + SAD had little or no influence on
baseline values for either MAP or the Den/Inn sodium, nor did they alter the
severity of ANG II hypertension. However, CPD totally abolished the fall in the
Den/Inn sodium in response to ANG II. Furthermore, after CPD + SAD, there was a
lower, rather than a higher, rate of sodium excretion from Inn vs. Den kidneys
during ANG II infusion (day 5 Den/Inn sodium = 2.02 +/- 0.14). These data suggest
that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic
nerve activity during ANG II hypertension and that in the absence of these
reflexes, ANG II has sustained renal sympathoexcitatory effects.
PMID- 11004015
TI - Portal GLP-1 administration in rats augments the insulin response to glucose via
neuronal mechanisms.
AB - The incretin glucagon-like peptide-1 (GLP-1)-(7---36) amide is an important
factor in prandial glucose homeostasis. Findings that GLP-1 is rapidly
inactivated led to the hypothesis that the target of GLP-1 is close to the site
of release. To investigate whether the target tissue is located in the
hepatoportal system, we administered GLP-1 with glucose into the portal vein of
rats and compared this with peripheral GLP-1 administration (jugular vein) and
studied the effects of blockers of the nervous system. Portal GLP-1 augmented the
insulin response to a portal glucose bolus by 81% (P < 0.01) and markedly
improved the glucose disposal rate (P < 0.05). Peripheral administration of GLP-1
produced a similar augmentation of the insulin response (88%) and of the glucose
disposal rate. However, only the effect of portal GLP-1 on insulin secretion was
blocked by the ganglionic blocker chlorisondamine. The data suggest that prandial
beta-cell stimulation by GLP-1 is evoked via a neural reflex triggered in the
hepatoportal system. Because absorbed nutrients and GLP-1 first appear in the
portal system, this mechanism may constitute a major pathway of GLP-1 action
during meals.
PMID- 11004016
TI - Synergy of L-arginine and growth hormone (GH)-releasing peptide-2 on GH release:
influence of gender.
AB - We test the hypotheses that 1) growth hormone (GH)-releasing peptide-2 (G)
synergizes with L-arginine (A), a compound putatively achieving selective
somatostatin withdrawal and 2) gender modulates this synergy on GH secretion. To
these ends, 18 young healthy volunteers (9 men and 9 early follicular phase
women) each received separate morning intravenous infusions of saline (S) or A
(30 g over 30 min) or G (1 microg/kg) or both, in randomly assigned order. Blood
was sampled at 10-min intervals for later chemiluminescence assay of serum GH
concentrations. Analysis of covariance revealed that the preinjection (basal)
serum GH concentrations significantly determined secretagogue responsiveness and
that sex (P = 0.02) and stimulus type (P < 0.001) determined the slope of this
relationship. Nested ANOVA applied to log-transformed measures of GH release
showed that gender determines 1) basal rates of GH secretion, 2) the magnitude of
the GH secretory response to A, 3) the rapidity of attaining the GH maximum, and
4) the magnitude or fold (but not absolute) elevation in GH secretion above
preinjection basal, as driven by the combination of A and G. In contrast, the
emergence of the G and A synergy is sex independent. We conclude that gender
modulates key facets of basal and A/G-stimulated GH secretion in young adults.
PMID- 11004017
TI - Synergy of L-arginine and GHRP-2 stimulation of growth hormone in men and women:
modulation by exercise.
AB - We investigated the ability of exercise, a multipathway, potent, physiological
stimulus for GH release, to alter the synergistic interaction of L-arginine (A)
and GH-related peptide (GHRP)-2 (G) observed at rest and the ability of gender to
further modulate this putative interaction. Subjects (9 men and 9 early
follicular phase women) completed 30 min of constant load aerobic exercise in
combination with intravenous infusions of saline (S), A (30 g over 30 min), G (1
microg/kg bolus), or both (AG) in separate study sessions in randomly assigned
order. Measures of GH release were logarithmically transformed for statistical
analysis. Similar to rest, exercise maintained the rank order (AG > G > A > S) of
effective stimulation of GH release for the key response measures in men or
women, a gender disparity in the time to reach the maximal serum GH
concentration, the calculated endogenous GH half-life, and the observed effect of
preinfusion (basal) serum GH concentrations on determining secretagogue
responsiveness. Exercise potentiated the individual stimulatory actions of A and
G, while blunting the relative magnitude of the synergistic (supra-additive)
interaction observed at rest. We infer from the present data that 1) exercise is
likely to induce release of both GHRH and somatostatin, 2) L-arginine may
facilitate the effect of exercise by limiting somatostatin release, 3) GHRP-2
could further enhance the stimulatory impact of exercise by opposing central
actions of somatostatin and/or heightening endogenous GHRH release, and 4) gender
strongly controls the relative but not absolute magnitude of A/G synergy both at
rest and after exercise.
PMID- 11004018
TI - Gastrointestinal motility during pregnancy: role of nitrergic component of NANC
nerves.
AB - This study evaluated whether increased release of nitric oxide (NO) from the
nitrergic component of the nonadrenergic, noncholinergic (NANC) nerves may be
partly responsible for the decrease in gastrointestinal motility observed during
pregnancy. Segments of fundal strip, ileum, and colon were obtained from
nonpregnant rats, rats in midpregnancy (days 9-11), and rats in late pregnancy
(days 18-20). NANC activity was studied by assessing changes in tone after
application of electric field stimulation (EFS). The role of NO was determined by
observing the effects of EFS in the presence and absence of the NO synthase (NOS)
inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the reversibility of
the effects of L-NAME by L-arginine. The magnitude of change in cGMP levels in
the tissues after application of EFS was also assessed. Our studies indicate that
there was increased magnitude of relaxation of isolated strips of rat gastric
fundus and rat colon, after application of EFS to tissues obtained only from
animals in late pregnancy. These results paralleled the changes in cGMP levels in
tissues. NOS activity in the gastric fundus was significantly increased in
animals in late pregnancy compared with nonpregnant controls. Our studies suggest
that the delay in gastric emptying and increase in colonic transit time observed
in rats during pregnancy may be caused in part by increased activity of the
nitrergic component of the NANC nerves innervating these organs.
PMID- 11004019
TI - Cardiovascular and metabolic responses of hypertensive and normotensive rats to
one week of cold exposure.
AB - Challenges to energy homeostasis, such as cold exposure, can have consequences
for both metabolic and cardiovascular functioning. We hypothesized that 1-wk cold
exposure (4 degrees C) would produce concurrent increases in metabolic rate
(VO(2); indirect calorimetry), heart rate (HR), and mean arterial blood pressure
(MAP) measured by telemetry. In the initial hours of change in ambient
temperature (T(a)), both spontaneously hypertensive rats (SHRs) and normotensive
Sprague-Dawley rats showed rapid increases (in cold) or decreases (in rewarming)
of VO(2), HR, and MAP, although the initial changes in MAP and HR were more
exaggerated in SHRs. Throughout cold exposure, HR, VO(2), food intake, and
locomotor activity remained elevated but MAP decreased in both strains,
particularly in the SHR. During rewarming, all measures normalized quickly in
both strains except MAP, which fell below baseline (hypotension) for the first
few days. The results indicate that variations of T(a) produce rapid changes in a
suite of cardiovascular and behavioral responses that have many similarities in
hypertensive and normotensive strains of rats. The findings are consistent with
the general concept that the cardiovascular responses to cold exposure in rats
are closely related to and perhaps a secondary consequence of the mechanisms
responsible for increasing heat production.
PMID- 11004020
TI - Expression of members of the multidrug resistance protein family in human term
placenta.
AB - The placenta serves, in part, as a barrier to exclude noxious substances from the
fetus. In humans, a single-layered syncytium of polarized trophoblast cells and
the fetal capillary endothelium separate the maternal and fetal circulations. P
glycoprotein is present in the syncytiotrophoblast throughout gestation,
consistent with a protective role that limits exposure of the fetus to
hydrophobic and cationic xenobiotics. We have examined whether members of the
multidrug resistance protein (MRP) family are expressed in term placenta. After
screening a placenta cDNA library, partial clones of MRP1, MRP2, and MRP3 were
identified. Immunofluorescence and immunoblotting studies demonstrated that MRP2
was localized to the apical syncytiotrophoblast membrane. MRP1 and MRP3 were
predominantly expressed in blood vessel endothelia with some evidence for
expression in the apical syncytiotrophoblast. ATP-dependent transport of the
anionic substrates dinitrophenyl-glutathione and estradiol-17-beta-glucuronide
was also demonstrated in apical syncytiotrophoblast membranes. Given the cellular
distribution of these transporters, we hypothesize that MRP isoforms serve to
protect fetal blood from entry of organic anions and to promote the excretion of
glutathione/glucuronide metabolites in the maternal circulation.
PMID- 11004021
TI - Opioids affect acquisition of LiCl-induced conditioned taste aversion:
involvement of OT and VP systems.
AB - Aversive properties of lithium chloride (LiCl) are mediated via pathways
comprising neurons of the nucleus of the solitary tract (NTS) and oxytocin (OT)
and vasopressin (VP) cells in the hypothalamic paraventricular (PVN) and
supraoptic (SON) nuclei. Because opioids act on brain regions that mediate
effects of LiCl, we evaluated whether administration of opioids shortly before
LiCl in rats influences 1) development of conditioned taste aversion (CTA) and 2)
activation of NTS neurons and OT/VP cells. Neuronal activation was assessed by
applying c-Fos immunohistochemical staining. Three opioids were used: morphine
(MOR), a mu-agonist, butorphanol tartrate (BT), a mixed mu/kappa-agonist, and
nociceptin/orphanin FQ (N/OFQ), which binds to an ORL1 receptor. BT and N/OFQ
completely blocked acquisition of CTA. MOR alleviated but did not eliminate the
aversive effects. Each of the opioids decreased LiCl-induced activation of NTS
neurons as well as OT and VP cells in the PVN and SON. We conclude that opioids
antagonize aversive properties of LiCl, presumably by suppressing activation of
pathways that encompass OT and VP cells and NTS neurons.
PMID- 11004022
TI - Angiotensin-converting enzyme inhibitor inhibits dehydration-enhanced fever
induced by endotoxin in rats.
AB - It has been reported that a host develops a marked fever under dehydrated
conditions compared with normally hydrated conditions (11). The present study was
carried out to investigate whether ANG II is involved in the enhancement seen in
dehydrated rats of the fever induced by bacterial endotoxin. The results showed
that intravenous injection of bacterial endotoxin produced a fever in dehydrated
rats (rats deprived of water for 24 h) that was significantly greater than that
seen in normally hydrated rats. In contrast, dehydration had no effect on the
fever induced by intravenous interleukin-1beta (IL-1beta). Under dehydrated
conditions, the enhanced endotoxin-induced fever was significantly inhibited by
the angiotensin-converting enzyme inhibitor lisinopril, but the IL-1beta fever
was not. These results suggest that the dehydration-induced enhancement of
endotoxin fever is due, at least in part, to the action of ANG II, which elicits
an increased production of pyrogenic cytokines such as IL-1.
PMID- 11004023
TI - Don't try this at home!
PMID- 11004024
TI - A century of regional analgesia in obstetrics.
PMID- 11004025
TI - The lack of benefit of tracheal extubation in the operating room after coronary
artery bypass surgery.
AB - Although early tracheal extubation in cardiac anesthesia is safe and cost
beneficial, questions still remain regarding how early after cardiac surgery
patients should be tracheally extubated (TE). Our objective was to determine the
effects on resource use if patients scheduled for coronary artery bypass grafting
have TE in the operating room (OR). We studied 100 consecutive patients
undergoing elective coronary artery bypass grafting, requiring extracorporeal
circulation, and those eligible for a fast-track pathway. At the end of the
procedure, the patients were evaluated for TE in the OR if they were
hemodynamically stable, were without significant bleeding, and fulfilled clinical
and blood gas analysis variables. Patients who did not meet the requirements had
TE in the intensive care unit (ICU). Fifty patients had TE in the OR and 50
patients in the ICU. Time in the OR after skin closure, ICU length of stay, and
postoperative length of stay were similar between the groups. Four patients (8%)
in the OR group were tracheally reintubated secondary to respiratory depression
(P = 0.11). Three patients (6%) in the OR group had postoperative myocardial
infarction, and one postoperative myocardial infarction (2%) occurred in the ICU
group (P = 0.61). All four patients recovered satisfactorily. The incidences of
other complications were similar between groups.
PMID- 11004026
TI - A comparison of superficial versus combined (superficial and deep) cervical
plexus block for carotid endarterectomy: a prospective, randomized study.
AB - Carotid endarterectomy may be performed by using cervical plexus blockade with
local anesthetic supplementation by the surgeon during surgery. Most
practitioners use either a superficial cervical plexus block or a combined
(superficial and deep) block, but it is unclear which offers the best operative
conditions or greatest patient satisfaction. We compared the two techniques in
patients undergoing carotid endarterectomy. Forty patients undergoing carotid
endarterectomy were randomized to receive either a superficial or a combined
cervical plexus block. Bupivacaine 0.375% to a total dose of 1.4 mg/kg was used.
The main outcome measure was the amount of supplemental lidocaine 1% used by the
surgeon. Subsidiary outcome measures were postoperative pain score, sedative and
analgesic requirements before and during surgery, and postoperative analgesic
requirements. Median supplemental lidocaine requirements were 100 mg (range 30
180 mg) in the superficial block group and 115 mg (range 30-250 mg) in the
combined block group. These differences were not statistically significant (Mann
Whitney U-test). There was no significant difference in the number of patients
needing postoperative analgesia between the groups (11 of 20 in the deep block
group versus 8 of 20 in the superficial block group) in the 24 h after surgery.
The median time to first analgesia in the superficial block group was 150 min,
more than in the combined block group (median time 45 min) but this difference,
although large, was not statistically significant (Mann-Whitney U-test). We found
no significant differences between the anesthetic techniques studied. All
patients reported satisfaction with the techniques.
PMID- 11004027
TI - Left stellate ganglion block has only small effects on left ventricular function
in awake dogs before and after induction of heart failure.
AB - Left stellate ganglion block (LSGB) results in acute sympathetic denervation of
the left ventricular (LV) posterobasal wall. We investigated the effects of LSGB
in chronically instrumented awake dogs before and after the induction of pacing
induced congestive heart failure. Twelve dogs were instrumented for measurement
of global hemodynamics [LV pressure (LVP)], its first derivative (dP/dt), cardiac
output (CO), and regional myocardial function (systolic posterobasal segment
length shortening, mean velocity [SLmv]). Before the induction of heart failure
(n = 12), LSGB did not affect CO [3.2+/-1.4 (control, mean +/- SD) vs. 3.3+/-1.6
L/min (LSGB, P = 0.45)] and SLmv (11.1+/-4.0 vs. 10.8+/-4.0 mm/s, P = 0.16), but
slightly reduced LVP (130+/-12 vs. 125+/-14 mm Hg, P = 0.04), dP/dt(max) (3614+/
755 vs. 3259+/-644 mm Hg/s, P = 0.003) and dP/dt(min) (-3153+/-663 vs. -2970+/
725 mm Hg/s, P = 0.03). During heart failure (n = 8), global hemodynamics [CO
(2.8+/-1.2 vs. 2.7+/-1.2 L/min, P = 0.04), LVP (119+/-6 vs. 112+/-9 mm Hg, P =
0.01), dP/dt(max) (1945+/-520 vs. 1824+/-554 mm Hg/s, P = 0.03) and dP/dt(min) (
2402+/-678 vs. -2243+/-683 mm Hg/s, P = 0.04)], as well as regional myocardial
function, were significantly different after LSGB [SLmv] (8.0+/-3.8 vs. 6.9+/-3.4
mm/s, P = 0.02)]. In conclusion, even during heart failure, the hemodynamic
changes after LSGB are small, confirming its broad margin of safety.
PMID- 11004028
TI - The effects of clonidine on human digital vasculature.
AB - Large concentrations of alpha(2) agonists cause vasoconstriction. However, the
threshold of the vasoconstrictive effect in humans is not known. We studied seven
volunteers to determine the lower limit of the vasoconstrictive effect of
clonidine. Subjects were studied while they were awake, and they were
anesthetized with propofol/alfentanil/N(2)O. Arterial blood pressure was
continuously monitored via radial arterial catheter and vasoconstriction via
finger volume plethysmography measuring infrared light transmitted through a
fingertip (LTF). Clonidine was administered, targeting plasma clonidine
concentrations of 0.3, 0.45, 0.68, 1.0, 1.5, and 2.25 ng/mL. The maximum change
from preclonidine values for systolic blood pressure (SBP) and LTF was analyzed
by using repeated measures analysis of variance. In awake subjects, clonidine
(2.25 ng/mL) decreased LTF by 14%+/-13% and SBP from 141+/-7 to 110+/-15 mm Hg
(P<0.0001). In contrast, clonidine (2.25 ng/mL) increased LTF in anesthetized
subjects by 21%+/-16% and SBP from 91+/-7 to 106+/-19 mm Hg (P<0.0001). We
conclude that the same dose of clonidine that decreased blood pressure and caused
vasodilation in awake subjects had the opposite effect in anesthetized subjects
with reduced sympathetic tone, increasing blood pressure and causing
vasoconstriction in human digital vasculature. Our findings suggest that the
lower threshold for clonidine-induced vasoconstriction in human digital
vasculature is 1.0 ng/mL.
PMID- 11004029
TI - Optison (FS069) disrupts the blood-brain barrier in rats.
AB - Optison is a new echocardiographic contrast agent, designed for IV injection,
that is very useful in delineating cardiac structures during ultrasound
examination. Because Optison could be a valuable adjunct in the diagnosis and
evaluation of congenital heart disease, this study was undertaken to assess its
effects on the blood-brain barrier when introduced directly in the cerebral
circulation, as might occur with some congenital lesions. In this study, Sprague
Dawley rats were anesthetized, and Optison, at various dosages, was injected into
the carotid artery. After this, Evans blue dye, a marker for blood-brain barrier
disruption, was injected at different time intervals. Gross and histologic
examination of the animals' brains revealed disruption of the blood-brain barrier
that appeared to be Optison-dosage-dependent. Although the mechanism for this
disruption is unclear, it may be related to the use of octofluoropropane gas used
in the Optison as a contrast medium. Further studies are necessary to determine
the pathologic consequences of Optison's effects on the blood-brain barrier.
PMID- 11004030
TI - Randomized safety studies of intravenous perflubron emulsion. I. Effects on
coagulation function in healthy volunteers.
AB - Previous perfluorocarbon (PFC) emulsions have been associated with transient
adverse events (i.e., platelet activation, decreased platelet count, febrile
responses, changes in hemodynamic function). The Phase I studies described in
this report were parallel, randomized, double-blinded, placebo-controlled studies
conducted in 48 healthy volunteers (n = 24 per study) with perflubron emulsion
(Oxygent; Alliance Pharmaceutical Corp., San Diego, CA). Because of the decreased
platelet counts observed with previous PFC emulsions and the intended use of
perflubron emulsion in surgical patients, these studies assessed postdosing
coagulation responses and hemostasis. PFC pharmacokinetic variables were also
evaluated. The primary endpoint for examination of coagulation effects was
prospectively defined as bleeding time. Subjects received either saline (3 mL/kg)
control, or perflubron emulsion at 1.2 g PFC/kg or 1.8 g PFC/kg, and were
evaluated for a 14-day period. No postinfusion changes in bleeding time or
differences in ex vivo agonist-induced platelet aggregation were observed. A 17%
reduction in platelet count was observed 3 days after dosing in the 1.8-g PFC/kg
group; levels recovered to baseline by Day 7. The intravascular half-life of
perflubron for the first 24 h was dose dependent: 9.4+/-2.2 h and 6.1+/-1.9 h in
the 1.8- and 1.2-g PFC/kg groups, respectively. Results indicate that this
perflubron emulsion did not affect coagulation function in healthy volunteers.
PMID- 11004031
TI - Randomized safety studies of intravenous perflubron emulsion. II. Effects on
immune function in healthy volunteers.
AB - Particle size distribution is a major determinant of particle clearance by the
mononuclear phagocytic system and the potential for concomitant activation of
resident macrophages. To test the safety of a second-generation perflubron-based
emulsion (60% perfluorocarbon [PFC] wt/vol; Oxygent [Alliance Pharmaceutical
Corp., San Diego, CA]) with a small mean particle size, two parallel, randomized,
double-blinded, placebo-controlled studies were conducted in 48 healthy
volunteers (n = 24 per study). The study described herein focuses on safety
concerning immune function. The primary endpoint was defined prospectively as
delayed hypersensitivity skin test responses with lymphocyte proliferative
responses to mitogenic stimulation providing a secondary measure for changes in
cell-mediated immunity. Subjects received either perflubron emulsion IV (1.2 g
PFC/kg or 1.8 g PFC/kg) or saline (3 mL/kg) control. Perflubron emulsion had no
effect on delayed hypersensitivity skin reactions, lymphocyte proliferative
potential, circulating immunoglobulins, complement activation, or plasma levels
of the inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 alpha,
and interleukin-1 beta. Perflubron emulsion was generally well tolerated,
although there was a dose-dependent increase in minor flu-like symptoms in the
perflubron treatment groups at 24 h after dosing. Increased serum levels of
interleukin-6 were observed in those subjects exhibiting febrile responses. The
clinical safety profile of perflubron emulsion supports its continued
investigation as a temporary oxygen carrier in surgical patients to reduce
exposure to allogeneic blood transfusion.
PMID- 11004032
TI - The effect of hydroxyethyl starch 200 kD on platelet function.
AB - We evaluated the effects of hydroxyethyl starch with a molecular weight of 200 kD
(HES 200 kD) on platelets to gain insight into the potential mechanisms involved
in the anticoagulant effects of HES 200 kD. Blood was obtained before and after
an IV infusion (10 mL/kg) of either saline (n = 15) or HES 200 kD (n = 15) in
otherwise healthy patients scheduled for minor elective surgery. Flow cytometry
was used to assess the expression of glycoprotein (GP) IIb-IIIa, GP Ib, and P
selectin on agonist-activated platelets. Overall platelet function was evaluated
by assessing thromboelastographic maximum amplitude (MA) in celite-activated
blood and platelet function analyzer-closure times by using collagen/adenosine
diphosphate cartridges. Saline infusion had no effects on platelet variables,
whereas HES 200 kD reduced GP IIb-IIIa expression and MA and prolonged platelet
function analyzer-closure times, without affecting the expression of P-selectin
and GP Ib. In vitro experiments extended these observations by a concentration
related inhibiting effect of HES 200 kD on GP IIb-IIIa expression. This study
demonstrates that cellular abnormalities with decreased availability of platelet
GP IIb-IIIa are involved in the anticoagulant effects of HES 200 kD.
PMID- 11004033
TI - The effect of clonidine premedication on hemodynamic responses to
microlaryngoscopy and rigid bronchoscopy.
AB - The usual hemodynamic response to laryngoscopy and bronchoscopy is an increase in
heart rate and arterial blood pressure. Previous work has reported that 10%-18%
of the patients develop ischemic ST segment changes during the procedure.
Therefore, we performed a prospective, randomized, double-blinded study in 36
patients scheduled for elective microlaryngeal and bronchoscopic surgical
procedures to evaluate the effects of 300-microg oral clonidine premedication (n
= 18) or placebo (n = 18) on the hemodynamic alterations and the incidence of
perioperative myocardial ischemic episodes. Myocardial ischemia was assessed by
using continuous electrocardiographic monitoring, beginning 30 min before, and
lasting until 24 h after the operation. During the procedure, patients receiving
placebo exhibited a significant increase (mean +/- SD) in arterial blood pressure
(the systolic increasing from 137+/-11 to 166+/-17 mm Hg, the diastolic
increasing from 80+/-11 to 97+/-14 mm Hg) and heart rate (increasing from 79+/-15
to 97+/-12 bpm) compared with the baseline and with the clonidine group. A dose
of 300-microg clonidine blunted the hemodynamic response to endoscopy.
Ventricular arrhythmias were more frequent in patients who were not premedicated
with clonidine. Two patients in the control group, but none in the clonidine
group, had evidence of myocardial ischemia. These data should encourage routine
premedication with clonidine in patients undergoing microlaryngoscopic and
bronchoscopic procedures.
PMID- 11004034
TI - Smaller-than-expected sevoflurane concentrations using the Sevotec 5 vaporizer at
low fill states and high fresh gas flows.
AB - Smaller-than-expected concentrations of sevoflurane were delivered by Sevotec 5
vaporizers (Datex-Ohmeda, Madison, WI) at low-fill states, 8% dialed
concentrations, and high fresh gas flows. Clinically, this would lead to
prolonged induction times. The risk of complications from prolonged inhaled
induction could be increased when using a vaporizer with these characteristics.
PMID- 11004035
TI - Specific genetic diseases at risk for sedation/anesthesia complications.
AB - We reviewed of a number of genetic diseases known or at risk for sedation or
anesthesia complications. Some of these conditions are relatively common (e.g.,
Down's syndrome) whereas others are rare or present with multiple congenital
anomalies that have an impact on health care delivery. We listed complications,
recommended presedation evaluations, and included checklist items to assist the
health care provider administering sedation and anesthesia. A better recognition
and awareness of risk factors associated with specific genetic diseases should
lessen the likelihood of complications during these procedures. IMPLICATIONS:
This article provides a brief description of potential problematic genetic
disorders and associated complications that may manifest during sedation or
anesthesia. Recommendations for presedation evaluation and checklist items are
given that may impact on the delivery of care for these patients.
PMID- 11004036
TI - Transient neurologic symptoms after epidural analgesia in a five-year-old child.
AB - Transient neurologic symptoms occurred in a five-year-old child after
discontinuation of epidural analgesia with bupivacaine and morphine, which had
been established for two days after thoracotomy. The symptoms resolved within 12
hours with acetaminophen.
PMID- 11004037
TI - Spinal anesthesia for gastrostomy in an infant with nemaline myopathy.
AB - IMPLICATIONS: We report a case of spinal anesthesia in an infant with nemaline
myopathy. Spinal anesthesia was administered to preempt the potential problems of
difficult tracheal intubation and prolonged mechanical ventilation secondary to
muscle weakness after the use of IV anesthetics in this patient.
PMID- 11004038
TI - A comparison of spinal, epidural, and general anesthesia for outpatient knee
arthroscopy.
AB - We compared general, epidural, and spinal anesthesia for outpatient knee
arthroscopy (excluding anterior cruciate ligament repairs). Forty-eight patients
(ASA physical status I-III) were randomized to receive either propofol-nitrous
oxide general anesthesia with a laryngeal mask airway with anesthetic depth
titrated to a bispectral index level of 40-60, 15-20 mL of 3% 2-chloroprocaine
epidural, or 75 mg of subarachnoid procaine with 20 microg fentanyl. All patients
were premedicated with <0.035 mg/kg midazolam and <1 microg/kg fentanyl and
received intraarticular bupivacaine and 15-30 mg of IV ketorolac during the
procedure. Recovery times, operating room turnover times, and patient
satisfaction were recorded by an observer using an objective scale for recovery
assessment and a verbal rating scale for satisfaction. Statistical analysis was
performed with analysis of variance and chi(2). Postanesthesia care unit
discharge times for the general and epidural groups were similar (general = 104+/
31 min, epidural = 92+/-18 min), whereas the spinal group had a longer recovery
time (146+/-52 min) (P = 0.0003). Patient satisfaction was equally good in all
three groups (P = 0.34). Room turnover times did not differ among groups (P =
0.16). There were no anesthetic failures or serious adverse events in any group.
Pruritus was more frequent in the spinal group (7 of 16 required treatment) than
in the general or epidural groups (no pruritus) (P<0.001). We conclude that
epidural anesthesia with 2-chloroprocaine provides comparable recovery and
discharge times to general anesthesia provided with propofol and nitrous oxide.
Spinal anesthesia with procaine and fentanyl is an effective alternative and is
associated with a longer discharge time and increased side effects. IMPLICATIONS:
For outpatient knee arthroscopy, anesthesia can be provided adequately with
regional or general anesthesia. Epidural and general anesthesia provide equal
recovery times and patient satisfaction, whereas spinal anesthesia may prolong
recovery and have increased side effects. The choice of anesthesia may depend
primarily on the patient's interest in being alert or asleep during the
procedure.
PMID- 11004039
TI - A comparison of minidose lidocaine-fentanyl and conventional-dose lidocaine
spinal anesthesia.
AB - The syndrome of transient neurologic symptoms (TNS) after spinal lidocaine has
been presumed to be a manifestation of local anesthetic neurotoxicity. Although
TNS is not associated with either lidocaine concentration or dose, its incidence
has never been examined with very small doses of spinal lidocaine. One hundred
ten adult ASA physical status I and II patients presenting for arthroscopic
surgery of the knee were randomly assigned to receive spinal anesthesia with
either 1% hypobaric lidocaine 50 mg (Group L50) or 1% hypobaric lidocaine 20 mg +
25 microg fentanyl (Group L20/F25). Hemodynamic data, block height and
regression, and time to first micturition and discharge were recorded. Follow-up
phone calls were made by a blinded researcher at 48-72 h using a standardized
questionnaire. Both groups had a median peak cephalad block level of T10.
Lidocaine 50 mg was associated with a greater decrease in systolic blood pressure
and a greater need for ephedrine. Time until block regression to the S2 dermatome
(80 vs. 110 min) and outpatient time to void (130 vs 162 min) and discharge (145
vs. 180 min) were faster in the L20/F25 group. Complaints of TNS were found in
32.7% of the patients in the L50 group and in 3.6% of the patients in the L20/F25
group. We conclude that spinal anesthesia with lidocaine 20 mg + fentanyl 25
microg provided adequate anesthesia with greater hemodynamic stability and faster
recovery than spinal anesthesia with lidocaine 50 mg. The incidence of TNS after
spinal lidocaine 20 mg + fentanyl 25 microg was significantly less than that
after spinal lidocaine 50 mg.
PMID- 11004040
TI - Bisulfite-containing propofol: is it a cost-effective alternative to Diprivan for
induction of anesthesia?
AB - Propofol (Diprivan(TM); AstraZeneca, Wilmington, DE) is a commonly used drug for
the induction of general anesthesia in the ambulatory setting. With the
availability of a new bisulfite-containing generic formulation of propofol,
questions have arisen regarding its cost effectiveness and safety compared with
Diprivan(TM). Two hundred healthy outpatients were randomly assigned, according
to a double-blinded protocol, to receive either Diprivan(TM) or bisulfite
containing propofol 1.5 mg/kg IV as part of a standardized induction sequence.
Maintenance of anesthesia consisted of either desflurane (4%-8% end-tidal) or
sevoflurane (1%-2% end-tidal) in combination with a remifentanil infusion (0.125
microg x kg(-1) x min(-1) IV). Patient assessments included pain on injection,
induction time, hemodynamic and bispectral electroencephalographic changes during
induction, emergence time, and incidence of postoperative nausea and vomiting.
The two propofol groups were comparable demographically, and the induction times
and bispectral index values during the induction were also similar. However, the
bisulfite-containing formulation was associated with less severe pain on
injection (5% vs 11%), with fewer patients recalling pain on injection after
surgery (38% vs. 51%, P<0.05). None of the patients manifested allergic-type
reactions after the induction of anesthesia. The acquisition cost (average
wholesale price in US dollars) of a 20-mL ampoule of Diprivan(TM) was $15
compared with $13 for the bisulfite-containing propofol formulation. Therefore,
we concluded that the bisulfite-containing formulation of propofol is a cost
effective alternative to Diprivan(TM) for the induction of outpatient anesthesia.
IMPLICATIONS: Bisulfite-containing propofol and Diprivan(TM) (AstraZeneca,
Wilmington, DE) were similar with respect to their induction characteristics;
however, the generic formulation was associated with a smaller incidence of
injection pain. Assuming that the drug costs are similar, these data suggest that
the bisulfite-containing formulation of propofol is a cost-effective alternative
to Diprivan(TM).
PMID- 11004041
TI - Recovery profiles and costs of anesthesia for outpatient unilateral inguinal
herniorrhaphy.
AB - The use of an ilioinguinal-hypogastric nerve block (IHNB) as part of a monitored
anesthesia care (MAC) technique has been associated with a rapid recovery profile
for outpatients undergoing inguinal herniorrhaphy procedures. This study was
designed to compare the cost-effectiveness of an IHNB-MAC technique with
standardized general and spinal anesthetics techniques for inguinal herniorrhaphy
in the ambulatory setting. We randomly assigned 81 consenting outpatients to
receive IHNB-MAC, general anesthesia, or spinal anesthesia. We evaluated recovery
times, 24-h postoperative side effects and associated incremental costs. Compared
with general and spinal anesthesia, patients receiving IHNB-MAC had the shortest
time-to-home readiness (133+/-68 min vs. 171+/-40 and 280+/-83 min), lowest pain
score at discharge (15+/-14 mm vs. 39+/-28 and 34+/-32 mm), and highest
satisfaction at 24-h follow-up (75% vs. 36% and 64%). The total anesthetic costs
were also the least in the IHNB-MAC group ($132.73+/-33.80 vs. $172.67+/-29.82
and $164.97+/-31.03). We concluded that IHNB-MAC is the most cost-effective
anesthetic technique for outpatients undergoing unilateral inguinal herniorrhaphy
with respect to speed of recovery, patient comfort, and associated incremental
costs.
PMID- 11004042
TI - Percutaneous tracheostomy: ciaglia blue rhino versus the basic ciaglia technique
of percutaneous dilational tracheostomy.
AB - Percutaneous dilational tracheostomy (PDT), according to Ciaglia's technique
described in 1985, has become the most popular technique for percutaneous
tracheostomy and is demonstrably as safe as surgical tracheostomy. In 1999, an
extensively modified technique of PDT was introduced, the Ciaglia Blue Rhino
(CBR; Cook Critical Care, Bloomington, IL), that consists of one-step dilation by
means of a curved dilator with hydrophilic coating. To compare CBR with the basic
technique of PDT, we performed a prospective, randomized trial in 50 critically
ill adults. Twenty-five of these patients had PDT, and 25 had CBR. Average
operating times were <3 min for CBR (range: 50-360 s) and <7 min for PDT (range:
4-20 min; P<0.0001). Tracheostomy was successfully completed in all patients.
When CBR was performed, 11 minor, nonlife-threatening complications were noted:
nine fractures of tracheal cartilage and two short periods of intraoperative
oxygen desaturation. During PDT, seven complications occurred, of which three
were potentially life-threatening: two injuries to the posterior tracheal wall,
one pneumothorax, two tracheal cartilage fractures (P< 0.05 vs CBR), one case of
bleeding, and one short episode of intraoperative oxygen desaturation. Regardless
of whether PDT or CBR was performed, oxygenation was not significantly affected,
and there was no infection of the tracheostoma. Based on our data, we conclude
that new CBR is more practicable than PDT. No life-threatening complications
occurred during CBR. IMPLICATIONS: To assess practicability and safety of the
Ciaglia Blue Rhino (Cook Critical Care, Bloomington, IL)-an extensively modified
technique of percutaneous dilatational tracheostomy-50 critically ill adults on
long-term ventilation underwent either new Ciaglia Blue Rhino or percutaneous
dilatational tracheostomy in a prospective, randomized clinical trial.
PMID- 11004043
TI - The good, the bad, and the ugly: should we completely banish human albumin from
our intensive care units?
AB - IMPLICATIONS: Human albumin is still widely used in critically ill patients for
volume replacement therapy or for correcting hypoproteinemia. Most meta-analyses
on the value of albumin administration are over 15 yr old and raise more
questions than they answer. With the help of a MEDLINE analysis, we examined more
recent studies in humans using albumin. Most of these studies have recommended a
very cautious use of albumin in critically ill patients.
PMID- 11004044
TI - Endotoxin augments cerebral hyperemic response to halothane by inducing nitric
oxide synthase and cyclooxygenase.
AB - We examined the cerebral hyperemic response to halothane after treatment with
bacterial lipopolysaccharide (LPS). To determine the involvement of inducible
nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), we tested whether the
effect of LPS on halothane-induced hyperemia was altered by pretreatment with the
selective iNOS inhibitor, aminoguanidine (100 mg/kg), COX-2 inhibitor, NS-398 (5
mg/kg), or enzyme expression inhibitor, dexamethasone (4 mg/kg). Further, we
examined whether the administration of a nitric oxide donor, diethylamine
NONOate, would change the cerebral hyperemic response of halothane. Sprague
Dawley rats were anesthetized with 0.5 minimum alveolar anesthetic concentration
of halothane and artificially ventilated. Regional cerebrocortical blood flow
(rCBF) was assessed by laser-Doppler flowmetry. LPS (1 mg/kg) was administered
intracerebroventricularly; artificial cerebrospinal fluid was used in controls.
Four hours after LPS infusion, iNOS and COX-2 messenger ribonucleic acid (mRNA)
levels (reverse transcription-polymerase chain reaction) and enzyme activities
(arginine-citrulline conversion and prostaglandin E(2) enzyme immunoassay) were
significantly increased. LPS enhanced halothane-induced 3.9 and 1.6-fold
increases in rCBF at 1.0 and 1.5 minimum alveolar concentration, respectively. Co
treatment with NS-398 attenuated, but aminoguanidine or dexamethasone abolished
the effect of LPS on halothane-induced rCBF increase. Diethylamine NONOate
mimicked the enhanced rCBF response to halothane. These results suggest that LPS
augmented halothane-induced cerebrocortical hyperemia by induction of iNOS and
COX-2.
PMID- 11004045
TI - A comparative study between a calcium channel blocker (Nicardipine) and a
combined alpha-beta-blocker (Labetalol) for the control of emergence hypertension
during craniotomy for tumor surgery.
AB - We compared the efficacy of the combination of enalaprilat/labetalol with that of
enalaprilat/nicardipine to prevent emergence postcraniotomy hypertension. A
prospective, randomized open labeled clinical trial was designed to compare the
incidence of breakthrough hypertension (systolic blood pressure [SBP] > 140 mm
Hg) and adverse effects (hypotension, tachycardia, and bradycardia) between the
two drug combinations. Secondarily, the effects of the drugs on SBP, mean blood
pressure, and diastolic blood pressure were evaluated over the course of the
study. Forty-two patients received enalaprilat 1.25 mg IV at dural closure
followed by either multidose nicardipine 2 mg IV or labetalol 5 mg IV to maintain
the SBP below 140 mm Hg. SBP was similarly controlled in both groups. There was a
marginally smaller incidence of failures and adverse effects with labetalol.
Blood pressure profiles were similar for both groups.
PMID- 11004046
TI - Arm pain as an unusual presentation of postdural puncture intracranial
hypotension.
AB - IMPLICATIONS: We report a case of a patient experiencing severe arm pain after
dural puncture. This complication has not been reported previously. The patient
was successfully treated with an epidural patch.
PMID- 11004047
TI - Crack cocaine, myocardial infarction, and troponin I levels at the time of
cesarean delivery.
AB - IMPLICATIONS: During the peripartum period, cocaine-abusing women are highly
susceptible to myocardial infarction. This report describes a case of myocardial
infarction diagnosed by increased troponin I levels in a pregnant patient with a
history of recent crack cocaine use and severe preeclampsia.
PMID- 11004048
TI - Postdural puncture headache: a randomized comparison of five spinal needles in
obstetric patients.
AB - This prospective, blinded, randomized study compares the incidence of postdural
puncture headache (PDPH) and the epidural blood patch (EBP) rate for five spinal
needles when used in obstetric patients. One thousand two women undergoing
elective cesarean delivery under spinal anesthesia were recruited. We used two
cutting needles: 26-gauge Atraucan and 25-gauge Quincke, and three pencil-point
needles: 24-gauge Gertie Marx (GM), 24-gauge Sprotte, and 25-gauge Whitacre. The
needle for each weekday was chosen randomly. Cutting needles were inserted
parallel to the dural fibers. The incidences of PDPH were, respectively, 5%,
8.7%, 4%, 2.8%, and 3.1% for Atraucan, Quincke, GM, Sprotte, and Whitacre needles
(P = 0.04, chi(2) analysis), and the corresponding EBP rates in those with PDPH
were 55%, 66%, 12.5%, 0%, and 0% (P = 0.000). The Quincke needle had a more
frequent PDPH rate than the Sprotte or the Whitacre needle (P = 0.02) and a more
frequent EBP rate than the GM, Sprotte, or the Whitacre needle (P = 0.01). The
Atraucan needle had a more frequent EBP rate than the Sprotte or Whitacre needle
(P = 0.05). Neither the PDPH rate nor the EBP rates differed among the pencil
point needles. The cost of EBP must be taken into consideration when choosing a
spinal needle. We conclude that pencil-point spinal needles should be used for
subarachnoid anesthesia in obstetric patients.
PMID- 11004049
TI - Drug use inefficiency: a hidden source of wasted health care dollars.
AB - A potential area for departmental savings is to minimize inefficient use of
pharmaceuticals. We recorded drug waste data for multiple drugs for a fiscal year
and surveyed providers' knowledge of departmental drug waste. Six large-cost or
large-volume use drugs were chosen for study: thiopental, succinylcholine,
rocuronium, atracurium, midazolam, and propofol. Amounts administered to patients
were collected for one year by using a computerized anesthesia record keeper.
Total drug distributed was the number of vials restocked by pharmacy for the
year. An efficiency index, the percent administered to patients, was calculated
for each drug. Drug administration to 25,481 patients was analyzed. Drug use
efficiency indices were: atracurium 29%; thiopental, 31%; succinylcholine, 33%;
propofol, 49%; midazolam, 53%; rocuronium, 61%. The total cost of unadministered
study drugs was $165,667, 26% of the expenditure for all drugs. Most dollars
wasted were for propofol, $80,863, and thiopental, $32,839. The reason most cited
for drug waste was the disposal of full, or partially full, syringes. Drug
wastage represents a significant portion of the entire anesthesia drug budget.
Waste reduction strategies should allow a portion of the "avoidable" waste to be
reduced. IMPLICATIONS: Unadministered drug amounts were measured for six study
drugs over one fiscal year and found to be significant; the cost of
unadministered drugs totaled $165,667. The reason most cited for waste was
disposal of full, or partially full, syringes.
PMID- 11004050
TI - A strategy to decide whether to move the last case of the day in an operating
room to another empty operating room to decrease overtime labor costs.
AB - We examined how to program an operating room (OR) information system to assist
the OR manager in deciding whether to move the last case of the day in one OR to
another OR that is empty to decrease overtime labor costs. We first developed a
statistical strategy to predict whether moving the case would decrease overtime
labor costs for first shift nurses and anesthesia providers. The strategy was
based on using historical case duration data stored in a surgical services
information system. Second, we estimated the incremental overtime labor costs
achieved if our strategy was used for moving cases versus movement of cases by an
OR manager who knew in advance exactly how long each case would last. We found
that if our strategy was used to decide whether to move cases, then depending on
parameter values, only 2.0 to 4.3 more min of overtime would be required per case
than if the OR manager had perfect retrospective knowledge of case durations. The
use of other information technologies to assist in the decision of whether to
move a case, such as real-time patient tracking information systems, closed
circuit cameras, or graphical airport-style displays can, on average, reduce
overtime by no more than only 2 to 4 min per case that can be moved.
IMPLICATIONS: The use of other information technologies to assist in the decision
of whether to move a case, such as real-time patient tracking information
systems, closed-circuit cameras, or graphical airport-style displays, can, on
average, reduce overtime by no more than only 2 to 4 min per case that can be
moved.
PMID- 11004051
TI - A magnetic resonance imaging study of modifications to the infraclavicular
brachial plexus block.
AB - A previously described infraclavicular brachial plexus block may be modified by
using a more lateral needle insertion point, while the patient abducts the arm 45
degrees or 90 degrees. In performing the modified block on patients abducting 45
degrees, we often had problems finding the cords of the brachial plexus.
Therefore, we designed an anatomic study to describe the ability of the
recommended needle direction to consistently reach the cords. Additionally, we
assessed the risk of penetrating the pleura by the needle. Magnetic resonance
images were obtained in 10 volunteers. From these images, a virtual reality model
of each volunteer was created, allowing precise positioning of a simulated needle
according to the modified block, without exposing the volunteers to actual needle
placement. In both arm positions, the recommended needle angle of 45 degrees to
the skin was too shallow to reach a defined target on the cords. Comparing the
two arm positions, target precision and risk of contacting the pleura were more
favorable with the greater arm abduction. We conclude that when the arm is
abducted to 90 degrees, a 65 degrees -needle angle to the skin appears optimal
for contacting the cords, still with a minimal risk of penetrating the pleura.
However, this needs to be confirmed by a clinical study.
PMID- 11004052
TI - Hyaluronidase as an adjuvant in bupivacaine-lidocaine mixture for
retrobulbar/peribulbar block.
AB - Hyaluronidase 7.5 IU/mL added to the local anesthetic improves peribulbar block,
but smaller concentrations have not been shown to be effective. In this
prospective, double-blinded study, 714 consecutive ocular surgery patients were
randomized into three groups: no hyaluronidase (n = 241), hyaluronidase 3.75
IU/mL (n = 244), and hyaluronidase 7.5 IU/mL (n = 229). Retrobulbar/peribulbar
block was performed with two injections of a 1:1 mixture of bupivacaine 0.75% and
lidocaine 2%, 6-8 mL. Patient data were collected on demographics, initial volume
of local anesthetic, need for supplementary block, and akinesia of the
anesthetized eye. When hyaluronidase was used (3.75 or 7.5 IU/mL), the initial
block was sufficient and the anesthetized eye was akinetic significantly more
often than in the group without hyaluronidase. The hyaluronidase groups (3.75 and
7.5 IU/mL) did not differ significantly in any respect. We conclude that the
addition of hyaluronidase 3.75 or 7.5 IU/mL improved the success of the initial
retrobulbar/peribulbar block and akinesia and reduced the need for supplementary
block. IMPLICATIONS: We conclude that the addition of hyaluronidase 3.75 or 7.5
IU/mL improved the success of the initial retrobulbar/peribulbar block and
akinesia and reduced the need for supplementary block.
PMID- 11004053
TI - A comparative study with oral nifedipine, intravenous nimodipine, and magnesium
sulfate in postoperative analgesia.
AB - We tested the ability of two L-type calcium channel blockers (nifedipine and
nimodipine) and the N-methyl D-aspartate natural antagonist magnesium to decrease
morphine requirements and pain in the postoperative period in 92 patients
undergoing elective colorectal surgery. In a randomized, double-blinded study,
patients were assigned to one of four groups. The control group received placebo.
The nifedipine group received 60 mg of oral nifedipine. The magnesium group
received an initial dose of 30 mg/kg followed by 10 mg x kg(-1) x h(-1) of
magnesium sulfate over 20 h. The nimodipine group received 30 microg x kg(-1) x
h(-1) of nimodipine over 20 h. Postoperative morphine consumption was assessed
for 48 h. Pain at rest and pain on movement were assessed up to the fifth day
postsurgery. There were no differences among groups in postoperative morphine
consumption at 12 and 24 h. The nifedipine group consumed more morphine than the
control and nimodipine groups during 24-48 h. Pain at rest scores were higher at
16 and 24 h in the nifedipine group than in the other three groups. Pain on
movement scores were lower at 72 h in the nimodipine group than in the control
and nifedipine groups. In conclusion, the perioperative application of oral
nifedipine, IV nimodipine, or IV magnesium sulfate failed to decrease
postoperative morphine requirements after colorectal surgery. IMPLICATIONS: The
increase of intracellular calcium plays a key role in spinal transmission of pain
and in the establishment of central sensitization. We examined the effects of
nifedipine, nimodipine, and magnesium sulfate in postoperative analgesia after
colorectal surgery. We found no differences in morphine consumption with the
administration of each drug alone.
PMID- 11004054
TI - Lidocaine disrupts axonal membrane of rat sciatic nerve in vitro.
AB - Highly concentrated lidocaine has been reported to induce irreversible loss of
membrane potential in crayfish nerve, which implies membrane disruption as one of
the direct mechanisms of lidocaine-induced neurotoxicity. To confirm lidocaine
induced membrane disruption in mammalian nerve, a lactate dehydrogenase (LDH)
leakage from rat sciatic nerve was measured in vitro. Before applying lidocaine,
the desheathed nerve was incubated for 60 min in Krebs-Ringer solution at 37
degrees C to examine basal LDH activity. It was then incubated in 80 mM lidocaine
solution at pH 7.3 for 15, 30, 60, or 120 min. Other nerves were immersed in 800
mM choline solution for 120 min. Total LDH activity per wet weight of nerve
tissue was assayed using spectrophotometry. It was also determined using nerves
cut into 10 segments and incubated in distilled water for 60 min. The LDH
activity in the lidocaine group showed a time-dependent increase. After the 60-
and 120-min incubation with lidocaine, the amount of LDH activity was
significantly increased compared with the choline group and was similar to that
of the group incubated in distilled water. We conclude that 80 mM lidocaine may
be sufficient to cause membrane damage and facilitate the leakage of enzymes from
cytoplasm. IMPLICATIONS: This study demonstrates that exposing the rat myelinated
nerve to lidocaine at a clinically used concentration for more than 30 min causes
enough membrane damage to allow enzyme leakage. In clinical practice, the
smallest effective dose should be used.
PMID- 11004055
TI - Percutaneous neuromodulation therapy: does the location of electrical stimulation
effect the acute analgesic response?
AB - We studied the effect of the location of electrical stimulation on the acute
analgesic response to percutaneous neuromodulation therapy in patients with
nonradiating neck pain. Sixty-eight patients received three different
nonpharmacologic modalities, namely "needles only" (neck), local (neck)
dermatomal stimulation, and remote (lower back) dermatomal stimulation in a
random sequence over the course of an 11-wk study period. All treatments were
given for 30 min, 3 times per week for 3 wk, with 1 wk "off" between each
modality. The assessment tools included the health status survey short form (SF
36) questionnaire, as well as 10-cm visual analog scales for assessing pain,
physical activity, and quality of sleep. The pain visual analog scale was
repeated 5-10 min after each treatment session. The daily oral nonopioid
analgesic requirements were recorded in the patient diary during the entire study
period. At the end of each 3-wk treatment block, the SF-36 questionnaire was
repeated. Compared with needles only and remote dermatomal stimulation, local
dermatomal stimulation produced a significantly greater decrease in pain (38%+/
17% vs 9%+/- 16% and 13%+/-18%), increase in physical activity (41%+/-21% vs 11%
+/-17% and 16%+/-15%), and improvement in the quality of sleep (34% +/-18% vs
7%+/-17% and 10%+/-18%) compared with baseline values (P<0.05). The need for oral
analgesic medications was decreased by an average of 6%+/-15%, 37%+/-18%, and
9%+/-13% during the 3-wk treatment period with the needle only, local dermatomal,
and remote dermatomal stimulation, respectively. The posttreatment SF-36 test
results revealed that all three modalities produced improvements compared with
the prestudy scores for both the physical component summary and mental component
summary. However, the magnitude of the changes in the physical component summary
and mental component summary with local dermatomal stimulation was significantly
greater (+7.9 and +3.6, respectively) than needle only (+3.4 and +1.7,
respectively) or remote dermatomal stimulation (+3.7 and +1.9, respectively). No
side effects were reported at the needle insertion sites. We conclude that
electrical stimulation at the specific dermatomal levels corresponding to the
local pathology produces greater short-term improvements in pain control,
physical activity, and quality of sleep in patients with chronic neck pain.
PMID- 11004056
TI - The effects of KRN5500, a spicamycin derivative, on neuropathic and nociceptive
pain models in rats.
AB - We studied the effects of a spicamycin derivative, KRN5500, on two animal models
of neuropathic pain (Chung and Bennett models) and a nociceptive pain model by
using Complete Freund's adjuvant. After the establishment of mechanical allodynia
by using the previously mentioned models, a single intraperitoneal injection of
KRN5500 produced significant attenuation of mechanical allodynia in both
neuropathic pain models. However, this effect was not observed in rats that had a
nociceptive injury (Complete Freund's adjuvant). Furthermore, this experimental
drug did not alter the mechanical pain threshold (by using von Frey filament
test) on normal, uninjured rats. We have demonstrated that KRN5500 may have value
in the treatment of neuropathic pain.
PMID- 11004057
TI - Memantine (a N-methyl-D-aspartate receptor antagonist) in the treatment of
neuropathic pain after amputation or surgery: a randomized, double-blinded, cross
over study.
AB - Evidence has accumulated that the N:-methyl-D-aspartate receptor system plays a
role in continuous and particularly, in stimulus-evoked pain after nerve injury.
We examined, in a randomized, double-blinded, cross-over fashion, the analgesic
effect of memantine (a N:-methyl-D-aspartate receptor antagonist) in a group of
patients with chronic pain after surgery. We randomized 19 patients to receive
either memantine or placebo in the first 5-wk treatment period. A washout period
of 4 wks was followed by another 5-wk treatment period with the opposite drug.
The dosage of drug was increased from 5 to 20 mg/d. Pain was recorded daily, with
the use of a 0-10 numeric rating scale. Before and at the end of each treatment
period, pain and sensitivity were also assessed by using the McGill Pain
Questionnaire, allodynia to touch, brush and cold, wind-up-like pain, and
thresholds to mechanical stimuli (pressure and von Frey hair). A total of 15
patients (12 amputees and three patients with other nerve injuries) completed the
study. There was no difference between memantine and placebo on any of the
outcome measures. We conclude that memantine at a dosage of 20 mg/d does not
reduce spontaneous or evoked pain in patients with nerve injury pain.
IMPLICATIONS: In a randomized, double-blinded and cross-over study, the analgesic
effect of memantine (a drug which reduces the excitability of sensitized neurons
in the dorsal horn) was examined in 19 patients with chronic pain after nerve
injury.
PMID- 11004058
TI - The effect of systemic lidocaine on pain and secondary hyperalgesia associated
with the heat/capsaicin sensitization model in healthy volunteers.
AB - Although effective in neuropathic pain, the efficacy of systemic lidocaine in non
neuropathic pain remains uncertain. We investigated the analgesic effect of
systemic lidocaine on the heat/capsaicin sensitization model of experimental pain
in 24 volunteers. Sensitization was produced by heating the skin to 45 degrees C
for 5 min, followed by a 30-min application of 0.075% capsaicin cream, and
maintained by periodically reheating the sensitized skin. Subjects received IV
lidocaine (bolus 2 mg/kg, then infusion 3 mg. kg. h), or saline for 85 min. Areas
of secondary hyperalgesia, heat pain detection thresholds, and painfulness of
stimulation with 45 degrees C for 1 min (long thermal stimulation) were
quantified. Systemic lidocaine reduced the area of secondary hyperalgesia to
brush, but not to von Frey hair stimulation. Lidocaine did not alter heat pain
detection thresholds or painfulness of long thermal stimulation in normal skin.
We conclude that, at infusion rates in the low- to mid-antiarrhythmic range,
lidocaine has no effect on acute nociceptive pain but does have a limited and
selective effect on secondary hyperalgesia. IMPLICATIONS: The efficacy of
systemic lidocaine in nonneuropathic pain remains uncertain. This study
investigates the effect of systemic lidocaine on experimental-induced
hyperalgesia in 25 volunteers. Hyperalgesia was induced by using an experimental
pain model that uses heat and capsaicin in combination. Systemic lidocaine showed
a selective effect on secondary hyperalgesia.
PMID- 11004059
TI - Defining segments and phases of a time capnogram.
AB - The division of a time capnogram into inspiratory and expiratory segments is
arbitrary and results in the inability of a time capnogram to detect rebreathing
instantaneously. Demarcation of a time capnogram into inspiratory and expiratory
components using gas flow signals will not only facilitate prompt detection of
rebreathing, but will also allow application of standardized and physiologically
appropriate nomenclature for better understanding and interpretation of time
capnograms. A Novametrix((R)) CO(2)-SMO plus respiratory profile monitor
(Novametrix Medical Systems, Wallingford, CT) was used to obtain a simultaneous
display of CO(2) and respiratory flow waveforms on a computer screen during
spontaneous and controlled ventilation using a circle system with the inspiratory
valve competent (no rebreathing) and with the valve displaced (rebreathing).
Because the response time of the CO(2) analyzer was similar to the response time
of the flow sensor, a comparison was made between the two waveforms to determine
the inspiratory segment (Phase 0) and the expiratory segment of the time
capnogram and its subdivisions (Phases I, II, and III). The end of expiration
almost coincides with the downslope of the CO(2) waveform in the capnograms when
there is no rebreathing. However, in the presence of rebreathing, the alveolar
plateau is prolonged and includes a part of inspiration (Phase 0), in addition to
the expiratory alveolar plateau (Phase III). IMPLICATIONS: Presently, the
division of a time capnogram into inspiratory and expiratory segments is
arbitrary. Demarcation of a time capnogram into various components using the gas
flow signals facilitates prompt detection of the cause of abnormal capnograms
that can widen the scope of future clinical applications of time capnography.
PMID- 11004060
TI - Aggressive warming reduces blood loss during hip arthroplasty.
AB - We evaluated the effects of aggressive warming and maintenance of normothermia on
surgical blood loss and allogeneic transfusion requirement. We randomly assigned
150 patients undergoing total hip arthroplasty with spinal anesthesia to
aggressive warming (to maintain a tympanic membrane temperature of 36.5 degrees
C) or conventional warming (36 degrees C). Autologous and allogeneic blood were
given to maintain a priori designated hematocrits. Blood loss was determined by a
blinded investigator based on sponge weight and scavenged cells; postoperative
loss was determined from drain output. Results were analyzed on an intention-to
treat basis. Average intraoperative core temperatures were warmer in the patients
assigned to aggressive warming (36.5 degrees +/- 0.3 degrees vs 36.1 degrees +/-
0.3 degrees C, P< 0.001). Mean arterial pressure was similar in each group
preoperatively, but was greater intraoperatively in the conventionally warmed
patients: 86+/-12 vs 80+/-9 mm Hg, P<0.001. Intraoperative blood loss was
significantly greater in the conventional warming (618 mL; interquartile range,
480-864 mL) than the aggressive warming group (488 mL; interquartile range, 368
721 mL; P: = 0.002), whereas postoperative blood loss did not differ in the two
groups. Total blood loss during surgery and over the first two postoperative days
was also significantly greater in the conventional warming group (1678 mL;
interquartile range, 1366-1965 mL) than in the aggressively warmed group (1,531
mL; interquartile range, 1055-1746 mL, P = 0.031). A total of 40 conventionally
warmed patients required 86 units of allogeneic red blood cells, whereas 29
aggressively warmed patients required 62 units (P = 0.051 and 0.061,
respectively). We conclude that aggressive intraoperative warming reduces blood
loss during hip arthroplasty. IMPLICATIONS: Aggressive warming better maintained
core temperature (36.5 degrees vs 36.1 degrees C) and slightly decreased
intraoperative blood pressure. Aggressive warming also decreased blood loss by
approximately 200 mL. Aggressive warming may thus, be beneficial in patients
undergoing hip arthroplasty.
PMID- 11004061
TI - Fractional distillation of acid contaminants from sevoflurane.
AB - On two occasions, sevoflurane distributed for clinical practice has been found to
be contaminated with compounds thought to include hydrogen fluoride (HF) and
silicon tetrafluoride (SiF(4)). Both compounds can produce pulmonary injury.
However, injury would require fractional distillation of the compounds during the
course of sevoflurane vaporization. We hypothesized that such distillation would
occur and that the compounds would vaporize more rapidly than would sevoflurane.
Thus, we tested whether fractional distillation occurs during vaporization of
sevoflurane containing HF or SiF(4), or from sevoflurane containing HF converted
to other compounds by contact with glass. Vaporization of < 10% of the
sevoflurane distilled 65%-99% of these compounds, SiF(4) distilling most rapidly,
HF (converted to other acidic compounds, including SiF(4)) distilling nearly as
rapidly, and HF slowest. Nuclear magnetic resonance studies indicated that HF
interaction with glass changed all HF to three other compounds, one being SiF(4)
and the others being unknown. HF and SiF4 distill from sevoflurane more rapidly
than sevoflurane is vaporized. Measurement of acidity after sevoflurane
administration may not reveal a previous presence of such contaminants.
PMID- 11004062
TI - The epileptogenic properties of the volatile anesthetics sevoflurane and
isoflurane in patients with epilepsy.
AB - No study comparing epileptogenicity of sevoflurane to other volatile anesthetics
has been performed. We compared the epileptogenic properties of sevoflurane to
isoflurane in patients with epilepsy. In 24 mentally and/or physically disabled
patients, 12 with epilepsy and 12 without epilepsy, electroencephalograms were
recorded under anesthesia with 1.0 minimum alveolar anesthetic concentration
(MAC), 1.5 MAC, and then 2.0 MAC sevoflurane or isoflurane under three
ventilatory conditions: (A) 100% oxygen, and end-tidal CO(2) partial pressure
(ETCO(2)) = 40 mm Hg, (B) 50% oxygen, 50% nitrous oxide, ETCO(2) = 40 mm Hg, and
(C) 100% oxygen, ETCO(2) = 20 mm Hg. Spike activity was evaluated as a spike-and
wave index (% durations of spike and wave). The spike-and-wave index increased
(P<0.05) from 1.99%+/-0.96% during 1.0 MAC sevoflurane to 6.14% +/- 4.45% during
2.0 MAC sevoflurane in (A) in the epilepsy group, while no spike activity was
observed in the nonepilepsy group. Only a few spikes were observed under
isoflurane anesthesia, 0.04% +/- 0.04% in (A), with no spikes in (B) and (C).
Supplementation with 50% nitrous oxide or hyperventilation (P<0.05) suppressed
the occurrence of spikes. Sevoflurane has a stronger epileptogenic property than
isoflurane, but nitrous oxide or hyperventilation counteracts this specific
epileptogenic property. IMPLICATIONS: The stronger epileptogenicity of
sevoflurane than isoflurane was confirmed in a controlled study in patients with
epilepsy. Hyperventilation and supplementation of nitrous oxide under sevoflurane
anesthesia suppressed epileptogenicity. A combination of sevoflurane and nitrous
oxide may be a safer method for seizure-prone patients than the use of
sevoflurane alone.
PMID- 11004063
TI - Interaction between volatile anesthetics and hypoxia in porcine tracheal smooth
muscle.
AB - We investigated the direct interaction between the volatile anesthetics,
isoflurane and sevoflurane, and hypoxia in porcine tracheal smooth muscle in
vitro by simultaneously measuring muscle tension and intracellular concentration
of free Ca(2+) ([Ca2+]i). Muscle tension was measured by using an isometric
transducer, and [Ca2+]i was measured by using fura-2, an indicator of Ca2+. Under
the condition of bubbling with 95% O2/5% CO2, [Ca2+]i was increased by 1 microM
carbachol with a concomitant contraction. Volatile anesthetics significantly
inhibited both carbachol-induced muscle contraction and increase in [Ca2+]i.
Hypoxia bubbled with 95% N(2)/5% CO2 inhibited the muscle contraction by 30% with
an increase in [Ca2+]i by 20%. Exposure to hypoxia substantially enhanced the
inhibitory effects of these anesthetics on carbachol-induced muscle contraction,
whereas the decreases in [Ca2+]i were significantly prevented by hypoxia. Under
Ca2+-free conditions, hypoxia significantly decreased the muscle contraction by
20%; however, it still increased [Ca2+]i by 15%. Exposure to the anesthetics
significantly enhanced the inhibitory effect of hypoxia on the muscle
contraction; however, it appeared to have little effect on [Ca2+]i. Hypoxia
inhibits airway smooth muscle contraction independently of intracellular Ca2+,
and it substantially potentiates the inhibitory effects of volatile anesthetics
on airway smooth muscle contraction. IMPLICATIONS: Hypoxia inhibits agonist
induced tracheal smooth muscle contraction with an increase in free Ca2+ [Ca2+]i,
which comes from intracellular Ca2+ stores. Hypoxia also potentiates the
inhibitory effect of volatile anesthetics on airway smooth muscle contraction.
Conversely, there is a possibility that the treatment of asthmatic patients with
oxygen partially attenuates the inhibitory effect of volatile anesthetics on
airway smooth muscle contractility.
PMID- 11004064
TI - A pilot study of left tracheal pulse oximetry.
AB - We tested the hypothesis that left tracheal pulse oximetry (SpO(2)) is more
accurate than finger SpO(2) when compared with oxygen saturation from arterial
blood samples (SaO(2)) in anesthetized patients with normal thoracic anatomy. We
also tested the hypothesis that tracheal oximetry readings are primarily derived
from the tracheal mucosa. We studied 20 hemodynamically stable, well oxygenated,
anesthetized patients with normal anatomy (ASA physical status I-III, 18-80 yr
old). A single-use pediatric pulse oximeter was attached to the left lateral
surface of a tracheal tube cuff. Tracheal and finger SpO(2) (dominant index
finger), and SaO(2) (nondominant radial artery) were taken with the intracuff
pressure at 0-60 cm H(2)O. Tracheal SpO(2) was the same as SaO(2) at an intracuff
pressure of 10-60 cm H(2)O, but was less when the intracuff pressure was zero
(P<0.0001). Tracheal SpO(2) was higher than finger SpO(2) at an intracuff
pressure of 10-60 cm H(2)O (all: P <0.001), but was lower when the intracuff
pressure was zero (P< 0.0001). SaO(2) was always higher than finger SaO(2)
(P<0.0001). Tracheal SpO(2) was lower at an intracuff pressure of zero (P<
0.0001), but was otherwise similar over the range of intracuff pressures. SaO(2)
and finger SpO(2) did not vary with intracuff pressure. Tracheal SpO(2) agrees
more closely with SaO(2) than finger SpO(2) at an intracuff pressure of 10-60 cm
H(2)O (mean difference < 0.2%). We conclude that left tracheal SpO(2) is feasible
and provides similar readings to arterial blood samples and more accurate
readings than finger oximetry in hemodynamically stable, well oxygenated,
anesthetized patients with normal thoracic anatomy. Tracheal oximetry readings
are not primarily derived from the tracheal mucosa. The technique merits further
evaluation.
PMID- 11004065
TI - Effects of nonimmobilizers and halothane on Caenorhabditis elegans.
AB - We studied the effects of two nonimmobilizers, a transitional compound, and
halothane on the nematode, Caenorhabditis elegans, by using reversible immobility
as an end point. By themselves, the nonimmobilizers did not immobilize any of the
four strains of animals tested. Toluene appears to be a transitional compound for
all strains tested. The additive effects of the nonimmobilizers with halothane
were also studied. Similar to results seen in studies of mice, the
nonimmobilizers were antagonistic to halothane in the wild type nematode.
However, the nonimmobilizers did not affect the 50% effective concentrations of
halothane for two other mutant strains. For halothane, the slopes of the dose
response curves were smaller in more sensitive strains compared with the wild
type. As in mammals, nonimmobilizers antagonize the effects of halothane on the
nematode, C. elegans. The variation in slopes in the response to halothane in
different strains is consistent with multiple sites of action. These results
support the use of C. elegans as a model for the study of anesthetics.
PMID- 11004066
TI - The nonimmobilizer 1,2-dichlorohexafluorocyclobutane does not affect
thermoregulation in the rat.
AB - Inhaled and other anesthetics profoundly affect the central nervous system,
causing amnesia, immobility in the face of noxious stimulation, and depression of
thermoregulation. Nonimmobilizers, inhaled compounds whose lipophilicity suggests
that they should be anesthetics, do not produce immobility, but they do cause
amnesia. Their effects on thermoregulation were the subject of the present study.
We gave eight rats isoflurane on one occasion and the nonimmobilizer 2N (1,2
dichlorolhexafluorocyclobutane) on another. We measured the effect of various
concentrations of each compound on thermoregulation provoked by body cooling. The
specific outcome was increased metabolism, as reflected in increased output of
carbon dioxide. Isoflurane decreased the temperature threshold for such increases
and the maximum response intensity, doing so in a concentration-dependent manner,
whereas 2N had a minimal or no effect at any concentration up to 0.9 minimum
alveolar concentration (estimated from its lipophilicity). Thus, 2N may be a
useful tool for studies of the mechanisms mediating the thermoregulatory
depression produced by anesthetics: 2N should not affect such a mechanism.
PMID- 11004067
TI - Does the ProSeal laryngeal mask airway prevent aspiration of regurgitated fluid?
AB - In this randomized, cross-over cadaver study, we determined whether a new airway
device, the ProSeal laryngeal mask airway (PLMA; Laryngeal Mask Company, Henley
on-Thames, UK), prevents aspiration of regurgitated fluid. We studied five male
and five female cadavers (6-24 h postmortem). The infusion set of a pressure
controlled, continuous flow pump was inserted into the upper esophagus and
ligated into place. Esophageal pressure (EP) was increased in 2-cm H(2)O
increments. This was performed without an airway device (control) and over a
range of cuff volumes (0-40 mL) for the classic laryngeal mask airway (LMA), the
PLMA with the drainage tube clamped (PLMA clamped) and unclamped (PLMA
unclamped). The EP at which fluid was first seen with a fiberoptic scope in the
hypopharynx (control), above or below the cuff, or in the drainage tube, was
noted. Mean EP at which fluid was seen without any airway device was 9 (range 8
10) cm H(2)O. EP at which fluid was seen was always higher for the PLMA clamped
and LMA compared with the control (all, P<0.0001). The mean EP at which fluid was
seen for the PLMA unclamped was similar to the control at 10 (range 8-13) cm
H(2)O. For the PLMA unclamped, fluid appeared from the drainage tube in all
cadavers at 10-40 mL cuff volume and in 8 of 10 cadavers at zero cuff volume.
Mean EP at which fluid was seen above the cuff was similar for the PLMA clamped
and LMA at 0-30 mL cuff volume, but was higher for PLMA clamped at 40-mL cuff
volume (81 vs 48 cm H(2)O, P = 0.006). Mean EP at which fluid was seen below the
cuff was similar at 0-10 mL cuff volume, but was higher for the PLMA clamped at
20, 30, and 40 mL cuff volume (62, 68, 73 vs. 46, 46, 46 cm H(2)O, respectively,
P<0.04). For the PLMA clamped and the LMA, fluid appeared simultaneously above
and below the cuff at all cuff volumes. We concluded that in the cadaver model,
the correctly placed PLMA allows fluid in the esophagus to bypass the pharynx and
mouth when the drainage tube is open. Both the LMA, and PLMA with a closed
drainage tube, attenuate liquid flow between the esophagus and pharynx. This may
have implications for airway protection in unconscious patients.
PMID- 11004068
TI - A modified intubating laryngeal mask for endotracheal tube exchange.
AB - IMPLICATIONS: It is often necessary to change a patient's breathing tube
(endotracheal tube). This can be a risky procedure. This report describes a
technique for changing an endotracheal tube by using a modified "intubating
laryngeal mask" (a commonly used airway and breathing device) and a fiberoptic
bronchoscope.
PMID- 11004069
TI - The efficacy and safety of EMLA cream for awake fiberoptic endotracheal
intubation.
AB - EMLA Cream (EC; Astra, Westborough, MA) has been widely used as a local
anesthetic. Limited safety information is available with respect to the
application of EC to the oral mucous membranes. The purpose of this pilot study
was to evaluate the efficacy and safety of EC when applied to oral mucosa for
fiberoptic intubation. Twenty ASA physical status I-IV patients (11 women and 9
men), 28-57 yr old, who were scheduled for awake, fiberoptic, intubation
participated in this open-label study. A total of 4 g of EC was used for 5 min
until the patient showed no evidence of a gag reflex (this was evaluated
clinically by the patient's acceptance of the William's airway and considered the
endpoint for assessing adequate topicalization of the oropharynx). The measured
peak plasma concentration of lidocaine or prilocaine did not reach toxic levels
in any patient. Methemoglobin levels did not exceed normal values (1.5%) in any
patient, and there was no relationship between methemoglobin levels and patient
weight, amount of EC used, measured peak plasma concentration, or times to
measured peak concentrations of prilocaine or lidocaine. We conclude that EC
provided satisfactory topical anesthesia allowing for successful oral fiberoptic
intubation in all patients and should be considered a safe alternative for
anesthetizing the airway of patients requiring awake oral fiberoptic intubation.
PMID- 11004070
TI - Bacitracin irrigation: a cause of anaphylaxis in the operating room.
AB - IMPLICATIONS: We report a unique case of acute anaphylaxis after mediastinal
irrigation with a dilute bacitracin solution.
PMID- 11004071
TI - The anesthetic management of a patient with paroxysmal nocturnal hemoglobinuria.
AB - IMPLICATIONS: This case report describes the anesthetic considerations for a
patient with paroxysmal nocturnal hemoglobinuria. Specific strategies to be
applied in the perioperative period to prevent hemolytic episodes and venous
thrombosis are also discussed.
PMID- 11004072
TI - An unusual case of malignant hyperthermia during desflurane anesthesia in an
African-American patient.
AB - IMPLICATIONS: Malignant hyperthermia is an uncommon, heritable condition
triggered by anesthesia and is followed by an increase in temperature that may be
fatal without prompt treatment. It is rare with desflurane and in black
individuals of African descent. We present a case of malignant hyperthermia in an
African-American patient during desflurane anesthesia.
PMID- 11004073
TI - The effect of sedative drugs on diaphragmatic contractility in dogs: propofol
versus midazolam.
AB - IMPLICATIONS: a sedative dose (0.1 mg x kg(-1) x h(-1)) of midazolam, compared
with a subhypnotic dose (1.5 mg x kg(-1) x h(-1)) of propofol, decreases the
contractility of the diaphragm in dogs.
PMID- 11004074
TI - Beware of air in the blood pump.
PMID- 11004075
TI - Muscle relaxants and 5-HT(3) receptors.
PMID- 11004076
TI - Inhibition of epidural morphine-induced pruritus by epidural droperidol.
PMID- 11004077
TI - No need for claims: facts rule performance of jet ventilation.
PMID- 11004078
TI - Sticker sedation.
PMID- 11004079
TI - Nitric oxide delivery system.
PMID- 11004080
TI - New cuff design prevents N2O diffusion.
PMID- 11004081
TI - NMDA receptor blockade: from the laboratory to clinical application.
PMID- 11004082
TI - Intravenous lidocaine and intrathecal opioids.
PMID- 11004083
TI - More about the Hawthorne effect.
PMID- 11004084
TI - Presence of placental tissue is necessary for TNG to provide uterine relaxation.
PMID- 11004085
TI - An unusual cause of failed sedation.
PMID- 11004086
TI - Teaching fiberoptic intubation in the pediatric patient.
PMID- 11004087
TI - Hypercapnea is an important adjuvant factor of oculocardiac reflex during
strabismus surgery.
PMID- 11004088
TI - Matrix metalloproteinases and their natural inhibitors.
PMID- 11004089
TI - The conundrum of sweet hyperopia.
PMID- 11004090
TI - Matrix metalloproteinases and their natural inhibitors in fibrovascular membranes
of proliferative diabetic retinopathy.
AB - AIM: To examine epiretinal membranes of proliferative diabetic retinopathy (PDR)
for the presence of selective matrix metalloproteinases (MMPs) and their natural
inhibitors (TIMPs), in order to determine whether neovascularisation and
fibrosis, characteristic of this complication of diabetes mellitus, are
associated with specific anomalies of MMP or TIMP expression. METHODS: The
presence of selected MMPs and TIMPs was investigated in 24 fibrovascular
epiretinal membranes of PDR, and the findings compared with that observed in 21
avascular epiretinal membranes of proliferative vitreoretinopathy (PVR) and five
normal retinas. Specimens were examined for deposition of interstitial
collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase A (MMP-2), gelatinase B
(MMP-9), and three tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, and
TIMP-3). RESULTS: The results showed that unlike normal retina, which
constitutively expresses MMP-1 and TIMP-2, a large proportion of PDR membranes (>
62%) stained for MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, and TIMP-3. There
were no differences in the expression of these molecules when compared with PVR
membranes. A characteristic staining for MMP-9 was observed within the
perivascular matrix of PDR membranes, and there was a significant increase in
TIMP-2 expression by PDR membranes (p= 0.036) when compared with PVR membranes.
CONCLUSIONS: The findings that MMPs involved in degradation of fibrovascular
tissue matrix, as well as TIMP-1 and TIMP-2, are found in a large proportion of
PDR membranes, and that their expression does not differ from that of PVR
membranes, suggest the existence of common pathways of extracellular matrix
degradation in pathological processes leading to retinal neovascularisation and
fibrosis.
PMID- 11004091
TI - Refractive changes in diabetic patients during intensive glycaemic control.
AB - AIMS: To evaluate the clinical course and the characteristics of transient
refractive error occurring during intensive glycaemic control of severe
hyperglycaemia. METHODS: 28 eyes of patients with persistent diabetes were
included in this prospective study. During the observation period, patients
underwent general ophthalmological examination and A-mode scan ultrasonography
was performed at each examination-at days 1, 3, and 7, and then once every week
or every other week until recovery of hyperopia. RESULTS: A transient hyperopic
change occurred in all patients receiving improved control after hyperglycaemia.
Hyperopic change developed a mean of 3.4 (SD 2. 0) days after the onset of
treatment, and reached a peak at 10.3 (6. 1) days, where the maximum hyperopic
change in an eye was 1.47 (0. 87) D (range 0.50-3.75 D). Recovery of the previous
refraction occurred between 14 and 84 days after the initial assessment. There
was a positive correlation between the magnitude of the maximum hyperopic change
and (1) the plasma glucose concentration on admission (p<0.01), (2) the HbA(1c)
level on admission (p<0.005), (3) the daily rate of plasma glucose reduction over
the first 7 days of treatment (p<0.001), (4) the number of days required for
hyperopia to reach its peak (p<0.001), and (5) the number of days required for
the development and resolution of hyperopic changes (p<0.0001). There was a
negative correlation between the maximum hyperopic change of an eye and baseline
value of refraction (p<0.01). During transient hyperopia, no significant changes
were observed in the radius of the anterior corneal curvature, axial length, lens
thickness, or depth of anterior chamber. CONCLUSIONS: The degree of transient
hyperopia associated with rapid correction of hyperglycaemia is highly dependent
on the rate of reduction of the plasma glucose level. A reduction of refractive
index in intraocular tissues, especially in lens, appears to be responsible for
this hyperopic change.
PMID- 11004092
TI - Patient characteristics, diagnosis, and treatment of non-contact lens related
Acanthamoeba keratitis.
AB - AIM: To review the clinical characteristics, diagnosis, and visual outcome in
patients with non-contact lens related Acanthamoeba keratitis and compare the
findings with reported series of contact lens associated Acanthamoeba keratitis.
METHODS: Medical and microbiology records of 39 consecutive patients with a
diagnosis of Acanthamoeba keratitis, at a tertiary eyecare centre in India
between January 1996 and June 1998, were analysed retrospectively. RESULTS: A
majority of the patients presented with poor visual acuity and large corneal
stromal infiltrates (mean size 38.20 (SD 26. 18) mm). A predisposing factor was
elicited in 19/39 (48.7%) patients (trauma 15, dirty water splash three, leaf
juice one). None of the patients had worn contact lenses. Most patients (26/39
(66. 6%)) came from a low socioeconomic background. Complaint of severe pain was
not a significant feature and radial keratoneuritis was seen in 1/39 (2.5%)
patients. A ring infiltrate was present in 41.1% of cases. A clinical diagnosis
of fungal keratitis was made in 45% of the patients before they were seen by us.
However, all patients were diagnosed microbiologically at our institute based on
demonstration of Acanthamoeba cysts in corneal scrapings (34/39) and/or culture
of Acanthamoeba (34/39). Treatment with biguanides (PHMB, 15/38 (39.4%), PHMB
with CHx, 23/38 (60.5%), one patient did not return for treatment) resulted in
healing with scar formation in 27 out of 31(87.0%) followed up patients (mean
time to healing 106.9 days). Overall visual outcome was poor with no statistical
difference between cases diagnosed within 30 days (early) or 30 days after (late)
start of symptoms. The visual outcome in cases requiring tissue adhesive (five)
and keratoplasty (three) was also poor. CONCLUSIONS: This is thought to be the
largest series of cases of Acanthamoeba keratitis in non-contact lens wearers. In
such cases, the disease is advanced at presentation in most patients,
pathognomonic clinical features are often not seen, disease progression is rapid,
and visual outcome is usually poor. Possible existence of Acanthamoeba pathotypes
specifically associated with non-contact lens keratitis and unique to certain
geographical areas is suggested.
PMID- 11004093
TI - Contrast sensitivity and glare disability by halogen light after monofocal and
multifocal lens implantation.
AB - BACKGROUND: Standard examination of contrast sensitivity under conditions of
glare disability is performed with incandescent light. A new halogen glare test
that simulates glare as seen with oncoming vehicle headlights was used to measure
glare disability in patients implanted with multifocal and monofocal intraocular
lenses (IOLs). METHODS: 28 patients with an average age of 69 years (SD 12 years)
were implanted with a monofocal IOL (SI-40NB, Allergan) and 28 patients with an
average of 66 years (12 years) were implanted with a refractive multifocal IOL
(Array-SA-40N, Allergan). All patients were followed for 5 months
postoperatively. Contrast sensitivity at four spatial frequencies (3, 6, 12, and
18 cycles per degree, cpd) with and without a glare source were measured using
the halogen glare test (CSV-1000 HGT). Statistical analysis was performed using
the two sample Wilcoxon test. The local significance level was set at 0.05.
RESULTS: When tested at the lowest spatial frequency (3 cpd) without halogen
glare, contrast sensitivity was lower in the multifocal group than in the
monofocal group (p=0.0292). With additional glare, there was no difference
between both groups. At all other spatial frequencies (6, 12, and 18 cpd), when
tested without halogen glare (6 cpd, p=0.5250; 12 cpd, p=0.8483; 18 cpd,
p=0.9496) and with moderate (3 cpd, p=0.7993; 6 cpd, p=0.4639; 12 cpd, p=0.7456;
18 cpd, p=1.0) and high halogen glare (3 cpd, p=0. 1513; 6 cpd, p=0.2016; 12 cpd,
p=0.3069; 18 cpd, p=0.9933), there was no statistically significant difference
between groups. Patients in both groups of age 70 or older had reduced contrast
sensitivity without halogen glare and with moderate and strong glare. When
monofocal and multifocal patients older than 70 years of age were analysed
separately, there was no statistically significant difference in contrast
sensitivity with and without glare. Astigmatism >1 dioptre had no significant
influence on contrast sensitivity and glare disability when monofocal and
multifocal eyes were compared. CONCLUSION: Reduced contrast sensitivity was found
in the multifocal group only at the lowest spatial frequency without halogen
glare. The monofocal and multifocal groups had no statistically significant
differences in contrast sensitivity with moderate and strong glare. These results
suggest no difference in glare disability induced by halogen light similar to
oncoming vehicle headlights for patients implanted with monofocal and multifocal
IOLs.
PMID- 11004094
TI - Anterior chamber depth measured by two methods in myopic and hyperopic phakic IOL
implant.
AB - AIM: To evaluate the accuracy and reliability of the optical versus ultrasonic
measurement of anterior chamber depth (ACD) in a group of patients affected by
high myopia or hyperopia, before phakic IOL implant. METHODS: 18 consecutive
patients (34 eyes) were enrolled in this study, and asked to undergo phakic IOL
implant to correct high myopia or hyperopia. The mean age was 29.5 (SD 3.4)
years, the male/female ratio was 10/8. 13 patients (24 eyes) were myopic (mean
myopia -16.17 (4.39) D, range -9 to -24 D), whereas five patients (10 eyes) were
hyperopic (mean hyperopia 7.4 (2.01) D, range 5.5-11 D). For each patient, ACD
was evaluated comparing an optical system (Orbscan topograph system) with a
standard A-scan ultrasound system. To evaluate the reliability of the two
methods, the average of three optical and 10 ultrasonic consecutive measurements
were considered. Statistical analysis was performed by means linear regression.
RESULTS: The average difference between optical and ultrasound values was 0.17
(0.1) mm (4.68% (2.52%)). There was a constant underestimation of the ACD with
the optical system compared with the ultrasound measurement, more evident in the
hyperopic eyes (5.20% (1. 95%)) than in myopic ones (4.46% (2.72%)). The
reliability of measurements, as showed by the standard deviation values, was
higher in the optical system (0.03 (0.02)) than in the ultrasound (0.1 (0. 05)),
with a statistical difference (p<0.001). The linear regression analysis between
optical and ultrasound measurements was 0.8992 (p<0. 0001). CONCLUSIONS: The
optical measurement of ACD is an accurate and reliable technique in high myopic
and hyperopic eyes. It gives a small underestimation of the ACD values, but it
could be preferable to the ultrasound technique, because it demonstrates more
repeatability and has the advantages of a non-contact technique.
PMID- 11004095
TI - Quantitative measurement of the PCCC area in the postoperative period.
AB - BACKGROUND/AIMS: The major complication of extracapsular cataract extraction
(ECCE) is posterior capsule opacification (PCO). Posterior continuous circular
capsulorhexis (PCCC) seems to be very promising in preventing PCO. This study was
aimed at determining if the PCCC area changes as a function of time and if pearl
formation could influence it. METHODS: 24 eyes of 23 patients underwent ECCE with
PCCC. Retroillumination photographs were taken at 6 months and then yearly. To
measure the PCCC area, the computerised program EPCO (evaluation of posterior
capsule opacification) was used. The ratio of the PCCC area in relation to the
IOL surface was calculated for the different time stages and the presence of
pearl formation was noted. Firstly, proportional changes in diameter were
compared in PCCC areas measured after 6 months and after 1 year (group I, n=13)
and after 1 year and 2 years (group II, n=14). Secondly, PCCC areas were compared
between two time stages in patients with (group III, n=19) and without pearl
formation (group IV, n=8). RESULTS: No statistically significant difference was
found in diameter change in either group. The PCCC area remains stabile between 6
months to 1 year and 1 year to 2 years. No differences are found between eyes
with or without pearl formation. CONCLUSIONS: The PCCC area remains stable as a
function of time and is not influenced by pearl formation.
PMID- 11004096
TI - Anterior uveitis and its relation to stress.
AB - BACKGROUND/AIMS: Idiopathic recurrent acute anterior uveitis (RAAU) is a common
reason for attendance at ophthalmic casualty departments. Patients who suffer
with this condition may have multiple recurrent episodes which are often
debilitating and necessitate time off work. If recurrences are identified early
and treatment initiated rapidly, the inflammation can be minimised and settles
quickly on topical treatment with a speedy functional recovery by the patient. It
has been our clinical impression that some patients with RAAU relate recurrences
of inflammation to psychological factors. Therefore stress could be a trigger
factor for recurrence, and at such times, patients should be alert to the early
signs of uveitis and seek prompt examination by an ophthalmologist. This study
tests the hypothesis that stressful life events are associated with the onset of
RAAU. METHODS: The number of stressful life events in patients presenting to the
casualty department with RAAU in the month immediately preceding symptom onset
was compared with a control group of patients with other ocular problems taken
from the casualty department using the Holmes and Rahe scale and the Spielberger
state-trait anxiety inventory. RESULTS: 35 patients with RAAU did not report a
higher number of stressful life events or higher levels of anxiety compared with
29 controls in this study on both Holmes and Rahe scale and Spielberger state
trait anxiety inventory. Scores for both groups were comparable with those
published for normal adults of the same age and sex. CONCLUSION: Stress was not
shown in this study to be involved in triggering the recurrence of idiopathic
acute anterior uveitis.
PMID- 11004097
TI - Bartonella henselae associated uveitis and HLA-B27.
AB - AIM: To investigate the frequency of HLA-B27 in patients with presumed Bartonella
henselae associated uveitis and to describe the clinical characteristics of HLA
B27 positive patients with uveitis and presumed ocular bartonellosis (POB).
METHODS: The diagnosis of POB was considered in 19 patients with unexplained
uveitis (except for the HLA-B27 association) and high positive IgG (titre
>/=1:900) and/or IgM (titre >/=1:250) antibodies against B henselae. In addition
to B henselae serology and HLA-B27 typing, all patients underwent an extensive
standard diagnostic screening procedure for uveitis and in all cases the results
were within the normal limits. The control group consisted of 25 consecutive
patients with panuveitis and negative B henselae serology. RESULTS: HLA-B27 was
positive in six of the 19 patients (32%) with POB in contrast to the 4% frequency
of HLA-B27 in the control group (p=0.03) and 8% prevalence of HLA-B27 in the
Dutch population (p=0.003). At the time of positive Bartonella serological
testing five of six HLA-B27 positive patients with POB had severe posterior
segment involvement with papillitis, macular oedema, and vitreitis. The duration
of intraocular inflammatory activity was more than 6 months in five HLA-B27
positive patients. Although four of the six HLA-B27 positive patients had
previous recurrent attacks of acute anterior uveitis, the clinical presentation
at the time of positive Bartonella serology differed, as illustrated by the
involvement of the posterior segment and chronic course of the ocular disease.
CONCLUSIONS: The frequency of HLA-B27 in patients with uveitis and serological
characteristics of acute infection with B henselae is higher than in the general
Dutch population. The findings of this study also suggest a relation between
infection with Bartonella species and HLA-B27.
PMID- 11004098
TI - Soluble Fas ligand and soluble Fas in ocular fluid of patients with uveitis.
AB - AIMS: To investigate the presence of soluble Fas ligand (sFasL) and soluble Fas
(sFas) in ocular fluid of patients with uveitis. METHODS: Samples of aqueous
humour (AH, n=17), vitreous fluid (n=9), and serum (n=60) were collected from
patients with uveitis which included Behcet's disease, Vogt-Koyanagi-Harada
disease, sarcoidosis, human T lymphotropic virus type 1 (HTLV-I) uveitis,
sympathetic ophthalmia, HLA-B27 associated acute anterior uveitis, and ocular
toxoplasmosis. The AH of patients with age related cataract without uveitis
obtained during cataract surgery was used as controls (n=20). The amounts of
sFasL and sFas were measured by enzyme linked immunosorbent assay. RESULTS:
Significant amounts of sFasL were detected in AH of patients with age related
cataract (non-uveitis group). sFasL was also detected in AH of patients with
uveitis, though the amounts were slightly lower than those in the non-uveitis
group. On the other hand, the levels of sFas in AH of patients with uveitis were
significantly higher than those in controls. As for the disease activity, the
levels of sFasL and sFas in the vitreous fluid of patients with active uveitis
were significantly higher than those in inactive uveitis. sFasL in the serum of
healthy donors and patients with uveitis was below detectable levels, except for
patients with HTLV-I uveitis who had significant amounts of sFasL in the serum.
The levels of sFas in the serum of patients with Behcet's disease, sarcoidosis,
and HTLV-I uveitis were significantly higher than those of healthy donors.
CONCLUSIONS: sFasL is present in the AH of non-uveitic eyes with age related
cataract. Intraocular levels of sFasL and sFas are significantly increased in
uveitis, particularly in active uveitis. These data suggest that intraocular
sFasL and sFas may have a regulatory role in uveitis.
PMID- 11004099
TI - Spontaneous cataract absorption in patients with leptospiral uveitis.
AB - AIMS: To describe the occurrence of spontaneous cataract absorption in patients
with leptospiral uveitis. METHODS: The records of patients with seropositive
leptospiral uveitis seen in the uveitis clinic at Aravind Eye Hospital between
January 1994 and December 1997 were reviewed retrospectively. RESULTS: During the
4 years of the study, 394 eyes of 276 patients with seropositive leptospiral
uveitis were identified. Of these, 54 eyes (13.7%) of 41 patients (14.9%) had a
final visual acuity of 20/40 or worse attributable to cataract formation. Of
these 54 eyes, 41 eyes (75.9%) had visually significant cataract on their first
visit to the uveitis clinic, and 13 eyes (24.1%) were noted to have cataract 1-6
months after presentation. Spontaneous absorption was observed in 10 eyes (18.5%)
of eight patients (19.5%), and occurred from 6 weeks to 18 months, with a median
of 5 months, after the onset of cataract. Of 12 035 consecutive, non-leptospiral,
non-traumatic, uveitic, control patients seen during the same 4 years of the
study, none showed spontaneous cataract absorption. CONCLUSION: Spontaneous
cataract absorption occurs in a significant number of patients with leptospiral
uveitis, and appears to be unique to this form of non-traumatic uveitis.
PMID- 11004100
TI - Ultrasound biomicroscopic analysis of pseudophakic pupillary block glaucoma
induced by Soemmering's ring.
AB - AIM: To perform ultrasound biomicroscopic analysis of pseudophakic pupillary
block glaucoma induced by lens capsule and a Soemmering's ring and its
resolution, and to elucidate the pathophysiology of this glaucoma. METHODS: A
woman with pseudophakic pupillary block glaucoma underwent successful
neodymium:YAG (Nd:YAG) laser photodisruption of the lens capsule through a laser
iridotomised coloboma with resolution of the pupillary block. The Humphrey
ultrasonic biomicroscope model 840 was employed to observe the anterior segment
before and after laser photodisruption. RESULTS: Ultrasound biomicroscopic
examination revealed the intraocular lens (IOL) was displaced forward, shallowing
the central anterior chamber. The anterior hyaloid face was relatively posterior
to the posterior capsule. The iris was in apposition to the anterior capsule,
which was in touch with the IOL optics. A massive Soemmering's ring, which
extended from the IOL optics to the ciliary processes, was displaced anteriorly.
The Soemmering's ring consisted of several tightly packed layers. The ciliary
processes rotated anteriorly. After Nd:YAG laser photodisruption of the capsule,
ultrasound biomicroscopic images showed the resolution of the pupillary block and
the anterior rotation of the ciliary process. The Soemmering's ring moved
posteriorly, and the layers in the ring became loose. CONCLUSIONS: A massive
Soemmering's ring may one of potential causes of pupillary block after cataract
surgery. Ultrasound biomicroscopy is potentially useful as a non-invasive
diagnostic technique for clinical diagnosis and differentiation between
Soemmering's ring induced pupillary block glaucoma and other forms of pupillary
block.
PMID- 11004101
TI - Pilot study of the multifocal electroretinogram in ocular hypertension.
AB - AIMS: To investigate the variation of retinal function in ocular hypertension
(OHT) using the multifocal electroretinogram (MERG), that can objectively assess
regional retinal responses using kernel analysis. METHODS: Patients with OHT were
recruited for 61 flash MERG recording. The first and second order kernel
responses were analysed and compared with responses from a normal group. All the
patients with OHT had full eye examinations and visual field analysis to ensure
they had no ocular pathology, apart from high IOP (>/= 22 mm Hg). RESULTS: In
OHT, both the first and the second order kernel responses showed a reduction in
magnitude compared with control values. The second order kernel responses showed
larger relative reduction of amplitude than the first order responses. In
addition, the macula showed a greater reduction in response than the periphery.
CONCLUSIONS: First order and second order kernel analyses are useful for
detecting changes of retinal response in OHT. The second order kernel analysis is
important in measuring the inner retinal activity and is an important factor in
detecting the early glaucoma case. Diminished macular response may be a useful
sign in early glaucomatous changes.
PMID- 11004102
TI - Comparison of visual field progression in patients with normal pressure glaucoma
between eyes with and without visual field loss that threatens fixation.
AB - AIM: To compare the frequency and site of visual field progression and changes in
visual acuity in patients with normal pressure glaucoma (NPG) with and without
pre-existing visual field loss. METHOD: Patients with normal tension glaucoma
were selected who had at least 10 visual fields over 5 or more years of follow up
and no other condition that might influence the visual field or visual acuity.
Alternate left and right eyes were selected from patients in random order. These
eyes were then subdivided according to visual field defect threatening fixation,
visual field defect not threatening fixation, and no visual field defect (fellow
eyes). Eyes were defined as showing a threat to fixation according to the
presence of a visual field defect involving one of more of four paracentral
visual field locations. Pointwise linear regression analysis was applied to each
visual field series using PROGRESSOR software. Progression of visual field loss
was defined as the appearance of a regression slope 1 dB per year or more with a
significance of p<0.01, which remained consistent with the addition of two of
three successive visual fields to the series. The number of patients showing
progression and the number where progression occurred in one of the four
paracentral visual field locations was noted. The number of eyes losing two or
more lines of Snellen visual acuity over the follow up period was also noted.
RESULTS: 174 eyes of 174 patients were selected. 106 eyes had visual field loss
threatening fixation, 46 eyes had visual field loss that did not threaten
fixation, and 22 were fellow eyes with normal visual fields. The median follow up
was 7.2 years. Eight eyes (36.4%) in the "normal visual fields" group, 31 eyes
(67.4%) in the "visual field loss away from fixation" group, and 87 eyes (82.1%)
in the "threat to fixation" group showed progression in any part of the visual
field. Two eyes (9.1%) in the "normal visual fields" group, nine eyes (19.6%) in
the "visual field loss away from fixation" group, and 45 eyes (42.5%) in the
"threat to fixation" group showed progression at "threat to fixation". The Cox
proportional hazards regression model showed an increased risk of progression at
any part of the visual field for female sex and a decreased risk for eyes with
normal visual fields. For progression at threat to fixation this model showed an
increased risk with pre-existing threat to fixation. Eyes from older patients and
those that went on to have progressive visual field loss at fixation were more
likely to lose two lines of Snellen visual acuity over the follow up period.
CONCLUSION: Since 20-30% of previously field damaged eyes and over 60% without
prior field loss fail to demonstrate progressive visual field damage over a long
follow up it is recommended that normal pressure glaucoma patients be monitored
for progression and that potentially harmful therapy be withheld until
progression is demonstrated. Although the presence of visual field loss that
threatens fixation does not constitute an increased risk of visual field
progression it does indicate an increased risk of further loss of visual field
close to fixation which is in turn associated with loss of central acuity. In the
light of this finding, patients with visual field loss that threatens fixation
should be managed more aggressively.
PMID- 11004103
TI - Utility of predictive equations for estimating the prevalence and incidence of
primary open angle glaucoma in the UK.
AB - AIMS: To assess the Tuck-Crick and the Quigley-Vitale predictive regression
equations against fresh independent real world data for estimating the prevalence
of primary open angle glaucoma (POAG) in the UK. To apply the equations to the
elderly population of England and Wales, for which there is sample survey data on
glaucoma, and demographic data. METHODS: Directly measured actual prevalence of
POAG in a population sample of 1530 people was compared with the predicted
prevalence derived by applying the Tuck-Crick and the Quigley-Vitale equations to
the sample data. The two equations were applied to the demographic data of the
population to project POAG prevalence and to derive 5 year cumulative incidence
for the elderly population. These were compared with estimates derived from the
local survey data. RESULTS: The actual directly measured prevalence of POAG in
the local sample was 3.01%. The Tuck-Crick estimate was 2. 74% (difference
0.27%), and the Quigley-Vitale was 3.50% (difference -0.49%). The three methods
projection from local survey data, Tuck-Crick, and Quigley-Vitale-gave point
estimates of 2.85% (228 526 cases), 2.71% (217 375 cases), and 3.50% (280 364
cases) respectively for the prevalence of POAG in the elderly population of
England and Wales (8 008 705 people aged 65 or older). Calculation of incidence
from age specific prevalence gave the following results: the numbers of new cases
of POAG expected (5 year cumulative incidence) in the elderly population were 71
146 and 94 485 for methods 2 and 3 respectively. CONCLUSIONS: The Tuck-Crick
predictive equation performed well when applied to fresh (independent) actual
data from a local sample survey using a particular definition for POAG, and its
usefulness for estimation of prevalence of POAG in England and Wales has been
demonstrated. The work on development of predictive equations has been very
promising and further refinements could be made when more fresh survey data
become available.
PMID- 11004105
TI - At what age could screening for familial retinoblastoma be stopped? A register
based study 1945-98.
AB - AIM: To evaluate until what age children in families with retinoblastoma should
be screened. METHODS: A register based cohort (n= 685) study of Dutch
retinoblastoma patients (1945-1998). The records of all familial hereditary
retinoblastoma patients from 1945 were reviewed and the age at diagnosis and
either they were screened from birth determined. RESULTS: 75 patients had the
familial hereditary form of retinoblastoma. The mean age at diagnosis in patients
with fundus screening (n=50) from birth on was 4.9 months (median 1.9 months;
range 1 day to 48 months). Thus, 4 years was the latest onset of familial
retinoblastoma properly evaluated from birth. This mean age was significantly
different (p<0.0001) from the mean age at diagnosis in patients without fundus
screening (n=25) from birth (mean 17.2 months; median 10.0 months; range 1.5-63.0
months). CONCLUSIONS: Ophthalmological screening of children and sibs at risk for
familial hereditary retinoblastoma is recommended until the age of 4 years in
order to detect retinoblastoma as early as possible.
PMID- 11004104
TI - Vasoproliferative tumours of the retina.
AB - BACKGROUND: Vasoproliferative tumours of the retina (VPTR) are benign tumours of
unknown origin, occurring mostly in otherwise healthy patients. VPTR may be
associated with other chorioretinal diseases, such as uveitis. The tumours, which
histologically represent reactive gliovascular proliferations, are characterised
by a pink to yellow appearance on funduscopy and are accompanied by exudative and
haemorrhagic changes of the retina. METHODS: 22 cases of VPTR in 21 patients were
examined with a follow up period between 1 month and 6 years. Ophthalmological
changes associated with VPTR were intraretinal and subretinal exudations (n=18),
exudative detachments of the surrounding sensory retina (n=13), intraretinal and
subretinal haemorrhages (n=10), exudative changes within the macula (n=10),
hyperpigmentation of the retinal pigment epithelium at the border of the
exudative retinal changes (n=9), and vitreous haemorrhages (n=4). Tumour biopsy
was performed in two cases. Treatment consisted of plaque radiotherapy (n=14),
plaque radiotherapy and cryotherapy (two), cryotherapy only (two), observation
(three), and enucleation in one case of a blind and painful eye. RESULTS:
Regression of the tumour and the associated exudative changes could be observed
in all treated cases. Visual acuity at last follow up improved two lines or more
in two cases, remained within two lines of the initial visual acuity in 15 cases,
and worsened in the remaining five. Histopathological examination of the biopsy
specimens and the tumour of the enucleated eye showed massive capillary
proliferation with perivascular spindle-shaped glial cells of retinal origin.
CONCLUSION: The correct diagnosis of VPTR is of importance as these lesions may
lead to visual loss. Further, VPTR must be differentiated from angiomas
associated with von Hippel-Lindau disease as well as from ocular and systemic
malignancies. Regression of tumour thickness and associated retinal changes can
be achieved with brachytherapy or cryotherapy.
PMID- 11004106
TI - Factors affecting pupil size after dilatation: the Twin Eye Study.
AB - BACKGROUND/AIMS: Well dilated pupils make eye surgery easier. A classic twin
study was established to examine the relative importance of genes and environment
in the variance of pupil size after mydriasis, and to examine the effects of
other factors such as age, iris colour, and refractive error. METHODS: 506 twin
pairs, 226 monozygotic (MZ) and 280 dizygotic (DZ), aged 49-79 (mean age 62.2
years, SD 5.7) were examined. Dilated pupil size was measured using a
standardised grid superimposed over digital retroillumination images taken 50-70
minutes after mydriasis using tropicamide 1% and phenylephrine 10%. Univariate
maximum likelihood model fitting was used to estimate genetic and environmental
variance components. RESULTS: Dilated pupil size was more highly correlated in MZ
compared with DZ twins (intraclass correlation coefficients 0.82 and 0.39
respectively). A model specifying additive genetic and unique environmental
factors showed the best fit to the data, yielding a heritability of 78-80%.
Individual environmental factors explained 18-19% of the variance in this
population. Age only accounted for 2-3% of the variance and refractive error and
iris colour did not significantly contribute to the variance. CONCLUSIONS: Pupil
size after mydriasis is largely genetically determined, with a heritability of up
to 80%.
PMID- 11004107
TI - Ocular features in Rubinstein-Taybi syndrome: investigation of 24 patients and
review of the literature.
AB - AIMS: To delineate the nature and frequency of ocular pathology in Rubinstein
Taybi syndrome (RTs). METHODS: Literature was searched for reports describing
ocular symptoms in patients with RTs. 24 RTs patients (out of a total of 73 Dutch
known RTs individuals) were selected for ophthalmological and
electrophysiological examination, selection being based only on the distance
between a patient's residence and the place of investigation. RESULTS: Most
frequently reported eye anomalies in the literature were lacrimal duct
obstruction, corneal abnormalities, congenital glaucoma, congenital cataract, and
colobomata. Abnormalities of almost any eye segment have been published in case
reports. Ophthalmological examination of 24 Dutch RTs patients showed a visual
acuity =0.3 in five patients. The most frequently found eye anomalies were
nasolacrimal duct problems (six patients), cataract (six patients, four
congenital), and retinal abnormalities (18 patients). VEPs showed an abnormal
waveform in 15 patients. It was possible to perform an ERG in 18 patients, of
whom 14 were abnormal (eight showed cone dysfunction, six cone-rod dysfunction).
CONCLUSIONS: Ocular abnormalities occur in the majority of RTs patients and can
be remarkably diverse. The high frequency of retinal dysfunction (78%) has not
been described before. With age, retinal as well as electrophysiological
abnormalities occur more frequently. In four patients no signs of retinal
dysfunction were observed, indicating phenotypic heterogeneity. Further
cytogenetic and molecular examination of the patients is needed before it becomes
clear if this also represents genetic heterogeneity. Because of the high
frequency of ocular abnormalities, visual function tests and electrophysiological
investigations should be performed in every RTs patient at regular intervals.
PMID- 11004108
TI - Use of a portable head mounted perimetry system to assess bedside visual fields.
AB - AIM: This study was designed to test the ability of a portable computer driven,
head mounted visual field testing system to perform automated perimetry on
patients at their bedside and to compare these results with the "gold standard"
for bedside examinations, confrontation visual fields. METHODS: The Kasha visual
field system is a portable automated perimeter which utilises a virtual reality
headset. 37 neurosurgery patients were examined at their bedside with a central
24 degree suprathreshold testing strategy after confrontation visual field
testing. The patterns of visual field defects were categorised and compared with
the results of confrontation testing. RESULTS: A total of 42 field examinations
were completed on 37 patients, and the average testing time for both eyes was 4.8
minutes with the perimetry system. Each of the 11 fields (100%) classified with
defects on confrontation testing was similarly categorised on head mounted
perimetry. 26 out of 31 (84%) visual fields were normal on both confrontation and
perimetry testing, while five out of the 31 fields (16%) which were full on
confrontation had visual field defects identified by head mounted perimetry.
CONCLUSION: The head mounted, automated perimetry system proved easily portable
and convenient for examining neurosurgical patients at their bedside in the
perioperative period. The device demonstrated equal sensitivity to confrontation
visual field testing methods in detecting field defects and offers the advantage
of standardised, quantifiable testing with graphic results for follow up
examinations.
PMID- 11004109
TI - Conjunctival inflammation in the chronic phase of Stevens-Johnson syndrome.
AB - AIMS: To understand the immunopathogenesis of the corneal conjunctivalisation in
Stevens-Johnson syndrome. METHODS: Conjunctivalised corneas from five patients
with Stevens-Johnson syndrome were studied immunohistochemically for several cell
surface antigens and two cytokines. Chemical injury specimens were also studied.
RESULTS: In all cases, immunohistochemistry revealed LFA-1, CD4, CD8, and CD68 on
subepithelial infiltrating cells. Also, HLA-DR and ICAM-1 were found on the
surfaces of epithelial cells, subepithelial infiltrating cells, subepithelial
fibroblasts, and endothelial cells in blood vessels. IFN-gamma was found in basal
epithelial cells; subepithelial cells and subepithelial extracellular matrix CD19
and IL4 were not detected. CONCLUSIONS: The infiltrating cell population in the
Stevens-Johnson syndrome samples includes macrophages, CD4 positive T cells, and
CD8 positive T cells. The cytokine expression pattern suggests CD4 positive T
cells are Th1 cells. The infiltrating cell population is similar in Stevens
Johnson syndrome and chemical injury conjunctivalised corneas.
PMID- 11004110
TI - Improvement of reproducibility of macular volume measurements using the
Heidelberg retinal tomograph.
AB - AIMS: To develop a more reproducible method of macular volumetric analysis in
order to facilitate serial monitoring of changes in retinal oedema with time.
METHODS: The Heidelberg retinal tomography (HRT) machine was used to scan the
macula of 20 normal subjects and 40 diabetics with macular oedema. The volume
above reference plane (VARP) within a 2 mm diameter and 3 mm diameter circle was
measured twice in each eye. The position of the circle to be measured was
carefully defined relative to major retinal vessels. As a modification to the
previously published technique, fluctuation of the height of the contour line
relative to the focal plane of the eye is compensated for by an adjustment of the
reference plane. The position of the circle was controlled relative to major
retinal vessels using an acetate. The reproducibility of VARP measurement was
assessed by three variables-the standard error of the difference on two isolated
VARP measurements, the standard error of the difference between the average of
three readings on two different occasions, as well as the coefficient of
variation (COV). RESULTS: Both the 2 mm and 3 mm circles showed good
reproducibility in VARP measurements. In normal subjects, the COV of VARP for 2
mm circles and 3 mm circles were 13% and 12% respectively. In patients with
macular oedema, the COV of VARP for 2 mm circles and 3 mm circles were 9% and 11%
respectively. CONCLUSION: The modification of VARP measurements between scans of
the same eye has improved the COV from 31% to 9% in eyes with diabetic macular
oedema.
PMID- 11004111
TI - Appraising evaluations of screening/diagnostic tests: the importance of the study
populations.
PMID- 11004112
TI - Tear secretion and tear film function in insulin dependent diabetics.
PMID- 11004114
TI - Developments in ophthalmology. Vol 30. immuno-ophthalmology
PMID- 11004113
TI - International poverty and health network
PMID- 11004115
TI - Ocular inflammation. Basic and clinical concepts
PMID- 11004116
TI - Stuttering: dysfunction in a complex and dynamic system.
PMID- 11004117
TI - Brain correlates of stuttering and syllable production. A PET performance
correlation analysis.
AB - To distinguish the neural systems of normal speech from those of stuttering, PET
images of brain blood flow were probed (correlated voxel-wise) with per-trial
speech-behaviour scores obtained during PET imaging. Two cohorts were studied: 10
right-handed men who stuttered and 10 right-handed, age- and sex-matched non
stuttering controls. Ninety PET blood flow images were obtained in each cohort
(nine per subject as three trials of each of three conditions) from which r-value
statistical parametric images (SPI?r?) were computed. Brain correlates of stutter
rate and syllable rate showed striking differences in both laterality and sign
(i.e. positive or negative correlations). Stutter-rate correlates, both positive
and negative, were strongly lateralized to the right cerebral and left cerebellar
hemispheres. Syllable correlates in both cohorts were bilateral, with a bias
towards the left cerebral and right cerebellar hemispheres, in keeping with the
left-cerebral dominance for language and motor skills typical of right-handed
subjects. For both stutters and syllables, the brain regions that were correlated
positively were those of speech production: the mouth representation in the
primary motor cortex; the supplementary motor area; the inferior lateral premotor
cortex (Broca's area); the anterior insula; and the cerebellum. The principal
difference between syllable-rate and stutter-rate positive correlates was
hemispheric laterality. A notable exception to this rule was that cerebellar
positive correlates for syllable rate were far more extensive in the stuttering
cohort than in the control cohort, which suggests a specific role for the
cerebellum in enabling fluent utterances in persons who stutter. Stutters were
negatively correlated with right-cerebral regions (superior and middle temporal
gyrus) associated with auditory perception and processing, regions which were
positively correlated with syllables in both the stuttering and control cohorts.
These findings support long-held theories that the brain correlates of stuttering
are the speech-motor regions of the non-dominant (right) cerebral hemisphere, and
extend this theory to include the non-dominant (left) cerebellar hemisphere. The
present findings also indicate a specific role of the cerebellum in the fluent
utterances of persons who stutter. Support is also offered for theories that
implicate auditory processing problems in stuttering.
PMID- 11004118
TI - TNFR1 signalling is critical for the development of demyelination and the
limitation of T-cell responses during immune-mediated CNS disease.
AB - In this review we summarize the essential findings about the function of tumour
necrosis factor (TNF) and its cognate receptors TNFR1 and TNFR2, and lymphotoxin
alpha (LT-alpha) ligands in immune-mediated CNS inflammation and demyelination.
The advent of homologous recombination technology in rodents provides a new
method which has been used during the last 5 years and has led to insights into
the pathophysiology of experimental autoimmune encephalomyelitis (EAE) in an
unprecedented way. Studies with knockout mice in which genes of the TNF
ligand/receptor superfamily are not expressed and studies with transgenic mice
overexpressing TNF and TNFR reveal the critical role of the TNFR1 signalling
pathway in the control of CNS demyelination and inflammation. These studies
provide novel findings and at the same time shed light on the complex
pathophysiology of EAE. Together, these findings may contribute to better
understanding of EAE and open new avenues in experimental therapies for multiple
sclerosis.
PMID- 11004119
TI - Expression of accessory molecules for T-cell activation in peripheral nerve of
patients with CIDP and vasculitic neuropathy.
AB - Vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy
(CIDP) are neuropathies characterized by a T-lymphocyte infiltrate in the
peripheral nerves. The microenvironment in which these T cells become activated,
and the molecules and cells that play a role in this process are incompletely
understood. Using immunohistochemical analysis, we studied the effect of the
presence of adhesion, costimulatory and antigen-presenting molecules on different
cell types as a precondition for local T-cell activation in human sural nerve
biopsies of seven patients with CIDP, three patients with vasculitic neuropathy
and three healthy controls. In biopsies from CIDP and vasculitic neuropathy
patients, but not in those from healthy controls, Schwann cells expressed the
adhesion/T-cell stimulatory molecule CD58 (LFA-3). The CD58 molecule was also
present on endothelial cells of all vasculitic neuropathy patients and one CIDP
patient. In biopsies from normal controls and patients, CD54 (ICAM-1) expression
was detectable on microvascular endothelial cells. In addition, expression of the
costimulatory molecule CD86 was detected on vascular tissue in patients with
vasculitic neuropathy. Although macrophages were always present in all subjects,
expression of the major histocompatibility complex (MHC)-like molecule CD1a by
macrophages was restricted to biopsies from two CIDP patients and one vasculitic
neuropathy patient. Unexpectedly, Schwann cells of a single vasculitis patient
strongly expressed CD1b, a molecule involved in the presentation of self
glycolipids to T cells. Schwann cells in biopsies from patients and normal
controls expressed high levels of the invariant chain, CD74, a molecule involved
in the intracellular sorting of MHC class II molecules. There was no evidence for
the presence of dendritic cells in sural nerve biopsies. These findings support a
model in which T-cell activation can be initiated and/or perpetuated locally in
sural nerve biopsies of patients with CIDP and vasculitic neuropathy, and predict
an important role for Schwann cells and endothelial cells.
PMID- 11004120
TI - Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in
inclusion body myositis persists over time. Studies in repeated muscle biopsies.
AB - Inclusion body myositis (IBM) is an inflammatory myopathy characterized
immunohistologically by prominent invasion of the non-necrotic, MHC-I class
antigen-expressing muscle fibres by CD8+ cytotoxic T cells. If the autoinvasive
CD8+ T cells are recruited specifically to the muscle and play a primary
pathogenetic role in the disease, a clonal restriction persisting over time
should be anticipated. In this study, we analysed the T-cell receptor (TCR) gene
usage by endomysial T lymphocytes in three sequential muscle biopsies from three
different IBM patients over a 19-22 month period using immunohistochemistry,
reverse transcription-polymerase chain reaction (RT-PCR) and sequence analysis of
the complementarity determining region (CDR3) of the amplified TCRs. We found
that CD8+ T lymphocytes persist in the endomysial infiltrates in all biopsies
during a 19-22 month period. The most frequently detected TCRs were the V beta 3,
V beta 5.1, V beta 6.7 and V beta 13 gene families, and several of the
autoinvasive CD8+ T cells expressed the TCRs V beta 6.7 and V beta 5.1. A
restricted usage of the examined V beta 6 gene family was found to persist in the
complementarity CDR3 determining region of the autoinvasive T cells over the 22
month period. Identical V beta 6 CDR3 gene arrangements were also found in the
multiple muscle biopsies from two of the three IBM patients. The results indicate
that in IBM there is a restricted expression of the TCR gene families among the
autoinvasive T lymphocytes with homologies in the CDR3 region that persist over
the course of the disease. A continuous, antigen-driven T-cell response is
prominent in the muscle of patients with IBM.
PMID- 11004121
TI - A second paroxysmal kinesigenic choreoathetosis locus (EKD2) mapping on 16q13
q22.1 indicates a family of genes which give rise to paroxysmal disorders on
human chromosome 16.
AB - Paroxysmal kinesigenic choreoathetosis (PKC) is a rare paroxysmal movement
disorder characterized by recurrent and brief attacks of choreiform or dystonic
movements triggered or exacerbated by sudden voluntary movements. Some patients
with PKC also have a history of infantile afebrile convulsions. PKC can be
sporadic, or familial with autosomal dominant inheritance. PKC has been mapped to
the pericentromeric region of human chromosome 16 in several Japanese families
and in an African-American family, to regions which overlap by 9.8 cM
(centiMorgan). Both regions overlap by 3.4 cM with a region containing a gene
responsible for 'infantile convulsions and paroxysmal choreoathetosis' (ICCA). We
have identified a second PKC locus (EKD2) on the long arm of chromosome 16 in a
large Indian family with PKC. A maximum two-point LOD score of 3.66
(recombination fraction = 0.00, penetrance = 0.80) was obtained between PKC and
D16S419. Haplotype and recombinant analysis localized EKD2 to a 15.8 cM region
between D16S685 and D16S503. This region does not overlap with that identified in
Japanese families, or with the ICCA locus. These results exclude one locus on
chromosome 16 which causes both the ICCA and PKC syndromes; this suggests that
there may be a cluster of genes on human chromosome 16 which lead to paroxysmal
disorders.
PMID- 11004122
TI - Early proton magnetic resonance spectroscopy in normal-appearing brain correlates
with outcome in patients following traumatic brain injury.
AB - The long-term clinical outcome following traumatic brain injury (TBI) can be
difficult to predict. Proton magnetic resonance spectroscopy (MRS) has previously
been used to demonstrate abnormalities in regions of white matter that appear
normal on conventional imaging in patients following TBI. We report MRI and MRS
studies of 26 patients performed at an early time point following injury (mean 12
days, n = 21) and at a later time point (mean 6.2 months, n = 15). The proton MRS
was acquired from the posterior part of a normal-appearing frontal lobe
containing predominantly white matter using stimulated echo acquisition mode to
localize, with a relaxation time of 3000 ms and echo time of 30 ms. At both the
early and late time points the N:-acetylaspartate/creatine ratio (NAA/Cr) was
significantly reduced (P = 0.03, P = 0.005, respectively), the choline/creatine
ratio (Cho/Cr) significantly increased (P = 0.001, P = 0.004, respectively) and
the myo-inositol/creatine ratio (Ins/Cr) significantly increased (P = 0.03, P =
0.03, respectively) compared with controls. There was a small, but significant,
further reduction (P = 0.02) in the NAA/Cr between the two studies in the 10
patients for whom data was available, at both time points. The NAA/Cr acquired at
the early time point significantly correlated with the clinical outcome of the
patients, assessed using either the Glasgow outcome scale (P = 0.005, n = 17) or
the disability rating scale (P < 0.001, n = 17). We conclude that there is a
sustained alteration in NAA and Cho. These findings provide possible evidence for
cellular injury (NAA loss reflecting neuroaxonal cell damage and raised Cho and
Ins reflecting glial proliferation) not visible by conventional imaging
techniques. This may be relevant to understanding the extent of disability
following TBI.
PMID- 11004123
TI - Visual hallucinatory syndromes and the anatomy of the visual brain.
AB - We have set out to identify phenomenological correlates of cerebral functional
architecture within Charles Bonnet syndrome (CBS) hallucinations by looking for
associations between specific hallucination categories. Thirty-four CBS patients
were examined with a structured interview/questionnaire to establish the presence
of 28 different pathological visual experiences. Associations between categories
of pathological experience were investigated by an exploratory factor analysis.
Twelve of the pathological experiences partitioned into three segregated
syndromic clusters. The first cluster consisted of hallucinations of extended
landscape scenes and small figures in costumes with hats; the second,
hallucinations of grotesque, disembodied and distorted faces with prominent eyes
and teeth; and the third, visual perseveration and delayed palinopsia. The three
visual psycho-syndromes mirror the segregation of hierarchical visual pathways
into streams and suggest a novel theoretical framework for future research into
the pathophysiology of neuropsychiatric syndromes.
PMID- 11004124
TI - Musical hallucinosis in acquired deafness. Phenomenology and brain substrate.
AB - Six subjects with musical hallucinations following acquired deafness are
described. The subjects all experienced the condition in the absence of any other
features to suggest epilepsy or psychosis. I propose a neuropsychological model
for the condition consistent with detailed observation of the subjects'
phenomenology. The model is based on spontaneous activity within a cognitive
module for the analysis of temporal pattern in segmented sound. Functional
imaging was carried out to test the hypothesis that musical hallucinosis is due
to activity within such a module, for which the neural substrate is a distributed
network distinct from the primary auditory cortex. PET was carried out on the six
subjects to identify areas where brain activity increased as a function of the
severity of the hallucination. In a group analysis, no effect was demonstrated in
the primary auditory cortices. Clusters of correlated activity were demonstrated
in the posterior temporal lobes, the right basal ganglia, the cerebellum and the
inferior frontal cortices. This network is similar to that previously
demonstrated during the normal perception and imagery of patterned-segmented
sound, and is consistent with the proposed neuropsychological and neural
mechanism.
PMID- 11004125
TI - Stride length regulation in Parkinson's disease: the use of extrinsic, visual
cues.
AB - It has been well documented that marked improvements in the hypokinetic gait
pattern of Parkinson's disease patients are possible with the use of appropriate
visual cues. This project served to evaluate Parkinson's disease gait performance
as well as residual processing capacity while using fixed or gait-regulated
visual cues. Three-dimensional kinematic, kinetic and electromyographic gait
analysis was carried out on 14 patients and 14 matched controls in baseline
conditions and with two types of visual cues: taped step length (SL) markers and
an individualized subject-mounted light device (SMLD). A probe reaction time
paradigm was invoked to assess residual processing capacity. Ratings of perceived
task load were also made using the NASA-Task Load Index. Stride length and gait
velocity were reduced in patients in baseline conditions. Both of these
parameters increased to control levels with the use of visual cues. These
alterations were generally accompanied by modifications of lower limb kinematics
and kinetics towards control subjects. Perceived task load was higher in all
conditions and was further elevated by the use of the SMLD for both groups.
Patients produced larger overall reaction times, although reaction time was not
different between baseline and SL marker conditions. Reaction time was increased
in both groups when using the SMLD. The overarching finding is that stride length
can be regulated in Parkinson's disease using stationary visual cues without
increased central processing capacity or perceived effort. This may occur via
utilization of visual feedback, reducing the patients' reliance on kinaesthetic
feedback for the regulation of movement amplitude.
PMID- 11004126
TI - Neuropsychological consequences of chronic bilateral stimulation of the
subthalamic nucleus in Parkinson's disease.
AB - The aim of this study was to examine possible neuropsychological changes in
patients with advanced idiopathic Parkinson's disease treated with bilateral deep
brain stimulation (DBS) of the subthalamic nucleus (STN). Eleven patients (age =
67 +/- 8 years, years with Parkinson's disease = 15 +/- 3, verbal IQ = 114 +/-
12) were evaluated (in their best 'on state') with tests assessing processes
reliant on the functional integrity of frontal striatal circuitry, prior to the
procedure (n = 11), at 3-6 months (n = 11) and at 9-12 months (n =10) post
operatively. Six of these patients were older than 69 years. Despite clinical
motor benefits at 3-6 months post-operative, significant declines were noted in
working memory, speed of mental processing, bimanual motor speed and co
ordination, set switching, phonemic fluency, long-term consolidation of verbal
material and the encoding of visuospatial material. Declines were more
consistently observed in patients who were older than 69 years, leading to a
mental state comparable with progressive supranuclear palsy. 'Frontal'
behavioural dyscontrol without the benefit of insight was also reported by half
(three of six) of the caregivers of the elderly subgroup. At 9-12 months
postoperative, only learning based on multiple trials had recovered. Tasks
reliant on the integrity of frontal striatal circuitry either did not recover or
gradually worsened over time. Bilateral STN DBS can have a negative impact on
various aspects of frontal executive functioning, especially in patients older
than 69 years. Future studies will evaluate a larger group of patients and
examine the possible reversibility of these effects by turning the DBS off.
PMID- 11004127
TI - Deficits in decision-making in patients with aneurysms of the anterior
communicating artery.
AB - Patients with aneurysmal subarachnoid haemorrhage (SAH) secondary to ruptured
anterior communicating artery aneurysms (ACoA) often suffer from
neuropsychological sequelae including personality and behavioural changes. In
this study, 31 patients with ruptured aneurysms of the ACoA resulting in SAH
[mean age 50.9 years, NART (National Adult Reading Test) IQ 108.7] were compared
with a group of 29 normal controls (mean age 51.9 years, NART IQ 109.7) on a
specific task of decision-making. A similar task has been imaged previously and
shown to activate regions involving the ventromedial prefrontal cortex. Patients
with ACoA rupture showed no significant difference from controls on the task in
their speed or quality of decision-making. They did, however, exhibit increased
risk-taking behaviour, placing higher bets in a measure of the task which
involved choices between actions associated with differing magnitudes of reward
and punishment. ACoA patients demonstrated true risk-taking behaviour as opposed
to simple impulsivity. Such a deficit in decision-making may be a result of
direct damage to the orbital prefrontal cortex itself (as a result of micro
ischaemia or infarction after ACoA aneurysmal rupture) or to a disconnection in
the ventromedial circuits from distant or generalized brain damage.
PMID- 11004128
TI - The regenerative deficit of peripheral nerves in experimental diabetes: its
extent, timing and possible mechanisms.
AB - Diabetes mellitus is reported to impair peripheral nerve regeneration, but the
extent, timing and selectivity of the deficit is unclear. We studied regeneration
of motor and sensory fibres in mice with experimental diabetes induced using
streptozotocin (STZ). The mouse model featured several advantages over its
counterpart in rats given STZ, while exhibiting the expected slowing of motor
conduction velocity. Serial studies addressed fibre regrowth for up to 10 weeks
after both sciatic nerve crush injury and complete sciatic nerve transection.
Following nerve crush, there was a delay in motor fibre reinnervation of tibial
innervated interosseous muscles of diabetics, manifest as a slow recovery of the
M-wave recorded from these muscles. Despite an apparent recovery in M-waves by 6
weeks, this was not accounted for by restitution of tibial axon numbers in
diabetic mice. Histological studies distal to crush or transection identified
substantial delays in the regrowth of the numbers and calibre of regenerating
myelinated fibres in diabetics for up to 8-10 weeks. Moreover, this delay was
observed in both the tibial (largely motor) and sural (non-motor) distal sciatic
branches. There was an associated delay in macrophage invasion and their later
resorption in the diabetic nerves, indicating that a potential mechanism of
impaired regeneration might be abnormal macrophage participation in nerve repair.
Our findings indicate that during nerve regeneration, diabetic motor and sensory
fibres have substantial and persistent deficits in regrowth associated with
abnormalities in macrophage participation.
PMID- 11004129
TI - Presentation of amyloidosis in carriers of the codon 692 mutation in the amyloid
precursor protein gene (APP692).
AB - Several mutations in the amyloid precursor protein (APP) gene may lead to either
Alzheimer's disease or cerebral haemorrhage due to congophilic amyloid angiopathy
(CAA). A single family is known in which both types of pathology are expressed
because of a missense mutation at codon 692 of the APP gene (APP692). Here we
describe the clinical and pathological expression of APP692 in eight patients
with the mutation. Furthermore, 21 first-degree relatives with an a priori risk
of 50% of being a carrier were tested for the APP692 mutation and studied for
presymptomatic signs by neurological examination, neuropsychological testing and
brain MRI. Patients with APP692 presented with haemorrhage, dementia or both. The
dementia in patients with the APP692 mutation was compatible with Alzheimer's
disease both clinically and neuropathologically. Of the 21 healthy relatives at
50% risk, five carried the APP692 mutation. The presymptomatic carriers showed a
subtle, non-significant impairment of cognitive function compared with relatives
without APP692. A significant increase in the number of periventricular and
subcortical white matter lesions at young age was seen in presymptomatic carriers
(mean age 26.4 years). The findings of this study suggest that a single (genetic)
mechanism may underlie the pathology of Alzheimer's disease and CAA. These
diseases are manifested subclinically by white matter pathology. Further insight
into the relationship between CAA and Alzheimer's disease may provide clues about
the aetiology of Alzheimer's disease.
PMID- 11004130
TI - Postural control in Parkinson's disease after unilateral posteroventral
pallidotomy.
AB - Postural control changes were studied in 27 patients with Parkinson's disease
after unilateral posteroventral pallidotomy (PVP). Patients were evaluated before
PVP and at 3, 6 and 12 months post-PVP, both 'off' and 'on' parkinsonian
medications, with selected evaluation tools representing functional performance,
functional balance and posturographic components of balance. The majority of
variables in the 'off' state were significantly improved at 3 months post-PVP.
Improvement was maintained at 6 months but had declined for some variables by the
12 month follow-up. Standing up from a chair (P = 0.009), the balance and gait
sections of the Performance-Oriented Assessment (P < or = 0.0004), and the limits
of stability (LOS) posturography variables (P < 0.0005) of the average time to
reach a target, the number of targets missed and the initial excursion distance
to the target (P = 0.029) retained significant improvement at the 12 month follow
up. When the patients were in the 'on' state, LOS posturography variables of
average time to target, average path length deviation, and the number of targets
missed were the only variables significantly improved at 3 months post-PVP (P =
0.013) and this improvement was maintained at 12 months post-PVP (P = 0.012
0.041). Unilateral PVP improves axial symptoms of Parkinson's disease involved in
functional performance such as gait disturbance as well as improving postural
stability in the 'off' state. Generally, the maximum improvement is seen at 3
months post-PVP with many variables remaining significantly improved at 12 months
post-PVP. Axial dyskinesias in the 'on' state are also significantly reduced with
the improvement maintained at 12 months post-PVP. These findings suggest that
unilateral pallidotomy is not only effective in abolishing levodopa-induced
dyskinesias, but that it also improves the axial signs of Parkinson's disease.
PMID- 11004131
TI - Opposite ictal perfusion patterns of subtracted SPECT. Hyperperfusion and
hypoperfusion.
AB - To investigate the patterns of ictal perfusion and related clinical factors,
single photon emission computed tomography (SPECT) subtraction was performed in
61 patients who had undergone epilepsy surgery. In addition to the ictal
hyperperfusion region, the ictal hypoperfusion area was obtained by SPECT
subtraction. The ictal perfusion patterns of subtracted SPECT were classified
into focal hyperperfusion, hyperperfusion-plus, combined hyperperfusion
hypoperfusion and focal hypoperfusion only. The concordance rate of seizure
localization was 91.8% in the combined analysis of ictal hyperperfusion
hypoperfusion by SPECT subtraction, 85.2% in hyperperfusion images of SPECT
subtraction and 68.9% in the visual inspection of ictal SPECT. Ictal
hypoperfusion occurred less frequently in temporal lobe epilepsy (TLE) than in
extra-TLE. Mesial temporal hyperperfusion alone was seen only in mesial TLE while
lateral temporal hyperperfusion alone was observed only in neocortical TLE.
Hippocampal sclerosis had a much lower incidence of ictal hypoperfusion than
other pathologies. Some patients showed ictal hypoperfusion at the epileptic
focus with ictal hyperperfusion in the neighbouring brain regions where ictal
discharges propagated. Hypoperfusion as well as hyperperfusion in ictal SPECT
should be considered for localizing epileptic focus. The mechanism of ictal
hypoperfusion could be an intra-ictal early exhaustion of seizure focus or a
steal phenomenon associated with the propagation of ictal discharges to adjacent
brain areas.
PMID- 11004132
TI - Worster-Drought syndrome, a mild tetraplegic perisylvian cerebral palsy. Review
of 47 cases.
AB - A retrospective case-note analysis was undertaken of 47 children with a
congenital upper motor neurone bulbar palsy (excluding pure speech dyspraxia) to
clarify the phenotype of Worster-Drought syndrome (WDS) and to record its
associated features and complications. The results revealed that the study
children had significant bulbar problems (with 80% still needing a modified diet
and a similar number using augmentative communication methods at last review).
There were also high rates of predictable bulbar complications (86% had
dribbling, 60% had glue ear, gastro-oesophageal reflux in 40%, history of poor
nutrition in 40% and aspiration in 40%). Most of the children had additional
complex impairments (91% had mild pyramidal tetraplegia, 81% learning
difficulties, 60% congenital defects, 41% neuropsychiatric problems and 28%
epilepsy). Over half of the children had significant medical problems in the
first year, but mean age at diagnosis was 6 years. There were no obvious causes
in pregnancy or birth. Six children had a family history of WDS and 32% (12/37)
had abnormal neuroimaging including five with bilateral perisylvian
polymicrogyria. In our experience, WDS is not uncommon, is relatively easily
diagnosed and is crucial not to miss as the management of these children's
multiple impairments is complex and requires a careful team approach. WDS falls
clearly within the cerebral palsies as a syndrome that includes motor impairment
arising from static damage to the brain in early life. The common presence of
cognitive, behavioural and seizure impairments strongly supports the cerebral
cortical (presumably perisylvian) localization. Its core elements are a
suprabulbar paresis, a mild spastic tetraplegia and a significant excess of
cognitive and behavioural impairments and epilepsy. The complete overlap in
phenotype between WDS and the bilateral perisylvian syndrome leads us to propose
that they are the same condition. WDS is startlingly absent from epidemiological
studies of the cerebral palsies and rarely diagnosed, presumably because of lack
of clinical awareness of the condition and lack of major gross motor impairments.
PMID- 11004133
TI - Haemophilus influenzae infection and Guillain-Barre syndrome.
AB - It has been reported recently that Haemophilus influenzae can elicit an axonal
form of Guillain-Barre syndrome. To investigate the incidence and features of H.
influenzae-related Guillain-Barre syndrome, anti-H. influenzae antibody titres
were measured by enzyme-linked immunosorbent assay (ELISA) in 46 consecutive
Japanese patients with Guillain-Barre syndrome, 49 normal controls, 24 patients
with multiple sclerosis and 27 patients with amyotrophic lateral sclerosis (ALS).
Whole bacteria of non-encapsulated (non-typable) H. influenzae isolated from one
of the Guillain-Barre syndrome patients was the antigen used. Elevated anti-H.
influenzae antibodies for two or three classes of IgG, IgM and IgA were found in
six (13%) Guillain-Barre syndrome patients, but not in the normal controls and
patients with multiple sclerosis or ALS. The incidence was significantly higher
in patients with Guillain-Barre syndrome than in the normal controls (P = 0.01)
and patients with multiple sclerosis or ALS (P = 0.009). Western blot analysis
confirmed that the H. influenzae-positive patients' IgG recognized the
lipopolysaccharides of H. influenzae. Guillain-Barre syndrome patients with anti
H. influenzae antibodies showed relatively uniform clinical and laboratory
features: prodromal respiratory infection, less frequent cranial and sensory
nerve involvement, pure motor axonal degeneration on electrophysiology, and
positivity for IgG anti-GM1 antibodies. Although the features were similar to
those in Guillain-Barre syndrome patients infected by Campylobacter jejuni, the
recoveries seemed to be better in patients with H. influenzae-related Guillain
Barre syndrome. It is concluded that a form of Guillain-Barre syndrome occurs
after respiratory infection by H. influenzae in the Japanese population. A
particular strain of non-typable H. influenzae has a ganglioside GM1-like
structure and elicits axonal Guillain-Barre syndrome similar to C. jejuni-related
Guillain-Barre syndrome.
PMID- 11004134
TI - Suppression of inflammation in primary systemic vasculitis restores vascular
endothelial function: lessons for atherosclerotic disease?
AB - BACKGROUND: Chronic inflammatory rheumatic disorders are associated with excess
cardiovascular mortality. This may result from arteriosclerosis following
inflammatory damage to the vessel wall by vasculitis. Our hypothesis that
vasculitis results in arteriosclerosis by causing vascular endothelial
dysfunction was tested in patients with primary systemic necrotizing vasculitis
(SNV). METHODS AND RESULTS: Endothelial function was assessed in cross-sectional
and longitudinal studies of patients with primary SNV by measuring flow-mediated,
endothelium-dependent brachial artery vasodilatation. These patients exhibited
marked endothelial dysfunction compared with controls. Remission induction in
patients with active primary SNV restored endothelial function. CONCLUSIONS:
Endothelial function is significantly impaired in adults with primary SNV,
supporting the hypothesis that premature arteriosclerosis in chronic inflammatory
rheumatic disorders results from endothelial dysfunction secondary to vasculitis.
Normalization of endothelial function after the treatment of primary SNV suggests
that early suppression of disease activity in chronic inflammatory rheumatic
disorders may reduce long-term vascular damage. The role of inflammation in
atheroma formation is increasingly appreciated; this work raises questions
regarding the potential for anti-inflammatory therapy in atherosclerosis itself.
PMID- 11004135
TI - Sympathetic activity and baroreflex sensitivity in young women taking oral
contraceptives.
AB - BACKGROUND: We tested sympathetic and cardiovagal baroreflex sensitivity during
the placebo or "low-hormone" phase (LH) and 2 to 3 weeks later during the "high
hormone" phase (HH) of oral contraceptive (OC) use in 9 women. METHODS AND
RESULTS: Sympathetic baroreflex sensitivity was assessed by intravenous doses of
sodium nitroprusside and phenylephrine and defined as the slope relating muscle
sympathetic nerve activity (by microneurography) and diastolic blood pressure.
Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval
and systolic blood pressure. No difference was observed for resting muscle
sympathetic nerve activity or plasma norepinephrine levels. However, sympathetic
baroreflex sensitivity was greater and mean arterial pressure was higher during
the LH than in the HH phase. Similarly, cardiovagal baroreflex sensitivity was
greater in the LH than in the HH phase. CONCLUSIONS: Sympathetic and cardiovagal
baroreflex sensitivities change during the 28-day course of OC use. Furthermore,
changes in baroreflex sensitivity with OC differ from changes in baroreflex
sensitivity during the normal menstrual cycle.
PMID- 11004137
TI - Three-dimensional intravascular ultrasound assessment of noninjured edges of beta
irradiated coronary segments.
AB - BACKGROUND: The "edge effect," late lumen loss at the margins of the treated
segment, has become an important issue in the field of coronary brachytherapy.
The aim of the present study was to assess the edge effect in noninjured margins
adjacent to the irradiated segments after catheter-based intracoronary beta
irradiation. METHODS AND RESULTS: Fifty-three vessels were assessed by means of 3
dimensional intravascular ultrasound after the procedure and at 6- to 8-month
follow-up. Fourteen vessels (placebo group) did not receive radiation (sham
source), whereas 39 vessels were irradiated. In the irradiated group, 48 edges (5
mm in length) were identified as noninjured, whereas 18 noninjured edges were
selected in the placebo group. We compared the volumetric intravascular
ultrasound measurements of the noninjured edges of the irradiated vessels with
the fully irradiated nonstented segments (IRS, n=27) (26-mm segments received the
prescribed 100% isodose) and the noninjured edges of the vessels of the placebo
patients. The lumen decreased (6 mm(3)) in the noninjured edges of the irradiated
vessels at follow-up (P:=0. 001). We observed a similar increase in plaque volume
in all segments: noninjured edges of the irradiated group (19.6%), noninjured
edges of the placebo group (21.5%), and IRS (21.0%). The total vessel volume
increased in the IRS in the 3 groups. No edge segment was subject to repeat
revascularization. CONCLUSIONS: The edge effect occurs in the noninjured margins
of radiation source train in both irradiated and placebo patients. Thus, low-dose
radiation may not play an important role in this phenomenon, whereas
nonmeasurable device injury may be considered a plausible alternative
explanation.
PMID- 11004136
TI - Prospective, randomized, infancy-onset trial of the effects of a low-saturated
fat, low-cholesterol diet on serum lipids and lipoproteins before school age: The
Special Turku Coronary Risk Factor Intervention Project (STRIP).
AB - BACKGROUND: We showed previously that repeated dietary counseling during the
first 3 years of life reduces the concentration of serum nonfasting cholesterol.
We have now extended the study to children 5 years of age and analyzed fasting
blood samples, enabling LDL cholesterol calculations for the first time. METHODS
AND RESULTS: Families of 7-month-old infants (n=1062) were randomized to a
control group (n=522) or an intervention group (n=540) that received
individualized dietary counseling with the aims of a fat intake of 30% to 35% of
daily energy, a saturated/monounsaturated/polyunsaturated fatty acid ratio of
1:1:1, and a cholesterol intake of <200 mg/d. Nutrient intakes were studied
biannually, nonfasting serum lipid values were studied annually, and fasting
values were studied at 5 years of age. The intervention children always had lower
intakes of saturated fat and cholesterol than the control children. The
intervention boys had 0.39 mmol/L (P:<0.0001) lower mean serum cholesterol values
than the control boys between 13 and 60 months of age, but among girls, the
difference was of marginal significance (0.15 mmol/L, P:=0.052). Five-year-old
intervention boys had 9% lower mean serum LDL cholesterol concentrations than the
control boys (P:=0.0002; 95% CI, -0.39 to -0.12 mmol/L), whereas no difference
was observed in girls. In both sexes, serum triglyceride concentrations were
similar in the 2 groups. CONCLUSIONS: The restriction of saturated fat and
cholesterol intake by repeated, individualized dietary counseling since infancy
resulted in lower serum total and LDL cholesterol concentrations at 5 years of
age. However, the effect was significant only in boys.
PMID- 11004138
TI - Flow cytometric monitoring of glycoprotein IIb/IIIa blockade and platelet
function in patients with acute myocardial infarction receiving reteplase,
abciximab, and ticlopidine: continuous platelet inhibition by the combination of
abciximab and ticlopidine.
AB - BACKGROUND: Improvement of thrombolysis may be achieved by concomitant strong
platelet inhibition. To monitor platelet function in patients with myocardial
infarction (n=46) who were treated with the fibrinolytic agent reteplase, the
glycoprotein (GP) IIb/IIIa blocker abciximab, and the ADP receptor antagonist
ticlopidine, we developed a flow cytometric assay. METHODS AND RESULTS: Binding
of abciximab to platelets was directly monitored as the percentage of platelets
stained by a goat anti-mouse antibody. Blood drawn 10 minutes and 2 hours after
the start of therapy with reteplase and abciximab and during the 12-hour infusion
of abciximab demonstrated a maximal blockade of GP IIb/IIIa (10 minutes, 86.2+/
10.3%; 12 hours, 85.8+/-7.1%). Starting at 24 hours, abciximab binding gradually
decreased (24 hours, 74.6+/-16.2%; 48 hours, 66.8+/-14.9%; 72 hours, 60.5+/
16.7%; 96 hours, 49.4+/-17.8%; 120 hours, 35.8+/-16. 4%; and 144 hours, 29.9+/
15.3%). Binding of a chicken anti-fibrinogen antibody to platelets, indicating
the level of functional blockade of GP IIb/IIIa, was inversely correlated with
the binding of abciximab (r=-0.72, P:<0.0001). In blood drawn at 10 minutes,
platelet aggregation was maximally inhibited but recovered within 48 hours even
if the majority of GP IIb/IIIa receptors were still blocked by abciximab.
Reteplase did not influence abciximab binding and did not activate platelets, as
measured by P-selectin expression, fibrinogen binding, and platelet aggregation.
Platelet inhibition that was achieved during the first 24 hours by abciximab was
directly maintained by additional treatment with ticlopidine. CONCLUSIONS: Flow
cytometric monitoring of platelet function allows differentiation of the effects
of reteplase, abciximab, and ticlopidine. The combination of abciximab and
ticlopidine is an attractive therapeutic strategy that provides a fast and
continuous platelet inhibition.
PMID- 11004139
TI - The unclampable ascending aorta in coronary artery bypass patients: A surgical
challenge of increasing frequency.
AB - BACKGROUND: The unclampable ascending aorta (UAA) is a condition increasingly
encountered during CABG procedures. We report our experience with CABG patients
with UAA and place particular emphasis on the preoperative diagnosis and surgical
management. METHODS AND RESULTS: UAA was diagnosed in 211 of 4812 consecutive
CABG patients (4.3%). On the basis of the chest radiograph, echocardiogram, and
coronary angiograph, a preoperative diagnosis was achieved in only 58 patients
(27.4%). An age of >70 years, diabetes, smoking, unstable angina, diffuse
coronaropathy, and peripheral vasculopathy were all predictors of UAA. Patients
were treated with hypothermic ventricular fibrillation (no-touch technique n=129)
or beating heart revascularization (no-pump technique n=82) depending on the
possibility of founding an arterial cannulation site. The overall in-hospital
mortality rate was 2.8% (6 of 211) with no differences between the 2 surgical
strategies. The no-touch technique was associated with a greater incidence of
neurological complications (stroke and transient ischemic attack), renal
insufficiency, and stay in the intensive care unit and hospital. However, at
midterm follow-up, more patients of the no-pump group had ischemia recurrence.
CONCLUSIONS: A preoperative diagnosis of UAA is achievable only in a minority of
patients, which highlights the necessity revising the current diagnostic
protocols. The use of the no-touch technique is associated with an high
perioperative risk but a superior possibility of complete revascularization,
whereas adoption of the no-pump strategy ensures a smoother postoperative course
at the expense of an higher incidence of ischemia recurrence.
PMID- 11004140
TI - Effect of amlodipine on the progression of atherosclerosis and the occurrence of
clinical events. PREVENT Investigators.
AB - BACKGROUND: The results of angiographic studies have suggested that calcium
channel-blocking agents may prevent new coronary lesion formation, the
progression of minimal lesions, or both. METHODS AND RESULTS: The Prospective
Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) was a
multicenter, randomized, placebo-controlled, double-masked clinical trial
designed to test whether amlodipine would slow the progression of early coronary
atherosclerosis in 825 patients with angiographically documented coronary artery
disease. The primary outcome was the average 36-month angiographic change in mean
minimal diameters of segments with a baseline diameter stenosis of 30%. A
secondary hypothesis was whether amlodipine would reduce the rate of
atherosclerosis in the carotid arteries as assessed with B-mode ultrasonography,
which measured intimal-medial thicknesses (IMT). The rates of clinical events
were also monitored. The placebo and amlodipine groups had nearly identical
average 36-month reductions in the minimal diameter: 0.084 versus 0.095 mm,
respectively (P:=0.38). In contrast, amlodipine had a significant effect in
slowing the 36-month progression of carotid artery atherosclerosis: the placebo
group experienced a 0.033-mm increase in IMT, whereas there was a 0. 0126-mm
decrease in the amlodipine group (P:=0.007). There was no treatment difference in
the rates of all-cause mortality or major cardiovascular events, although
amlodipine use was associated with fewer cases of unstable angina and coronary
revascularization. CONCLUSIONS: Amlodipine has no demonstrable effect on
angiographic progression of coronary atherosclerosis or the risk of major
cardiovascular events but is associated with fewer hospitalizations for unstable
angina and revascularization.
PMID- 11004141
TI - Explanation for the decline in coronary heart disease mortality rates in
Auckland, New Zealand, between 1982 and 1993.
AB - BACKGROUND: We sought to determine how much of the recent, substantial fall in
coronary heart disease (CHD) mortality rates in New Zealand can be attributed to
"evidence-based" medical and surgical treatments and how much can be attributed
to cardiovascular risk factor reductions. METHODS AND RESULTS: A cell-based
mortality model was developed and refined. This model combined (1) the published
effectiveness of cardiological treatments and risk factor reductions with (2)
data on all medical and surgical treatments administered to all CHD patients and
(3) trends in population cardiovascular risk factors (principally smoking,
cholesterol, and hypertension) from 1982 to 1993 in Auckland, New Zealand
(population 996 000). Between 1982 and 1993, CHD mortality rates fell by 23.6%,
with 671 fewer CHD deaths than expected from baseline mortality rates in 1982.
Forty-six percent of this fall was attributed to treatments (acute myocardial
infarction 12%, secondary prevention 12%, hypertension 7%, heart failure 6%, and
angina 9%), and 54% was attributed to risk factor reductions (smoking 30%,
cholesterol 12%, population blood pressure 8%, and other, unidentified factors
4%). These proportions remained relatively consistent after a robust sensitivity
analysis. CONCLUSIONS: Approximately half the CHD mortality rate fall in
Auckland, New Zealand, was attributed to medical therapies, and approximately
half was attributed to reductions in major risk factors. These findings emphasize
the importance of a comprehensive strategy that maximizes the population coverage
of effective treatments and actively promotes a prevention program, particularly
for smoking, diet, and blood pressure reduction.
PMID- 11004142
TI - Differential pacing for distinguishing block from persistent conduction through
an ablation line.
AB - BACKGROUND: Because complete linear conduction block is necessary to minimize the
recurrence of reentrant tachycardias such as typical atrial flutter, we
investigated a simple technique to recognize a persistent gap or complete linear
block. METHODS AND RESULTS: We prospectively evaluated cavotricuspid isthmus
conduction in 50 patients (age 63+/-8 years, 43 men) after radiofrequency
ablation. The distal and proximal bipoles of a quadripolar catheter placed close
to the ablation line were successively stimulated during recording from the
ablation line. We hypothesized that because the initial and terminal components
of local potentials reflected activation at the ipsilateral and contralateral
borders of the ablation lesion, a change to a more proximal pacing site without
moving the catheter would prolong the stimulus to the initial component timing,
whereas the response of the terminal component would depend on the presence of
block or persistent conduction. A shortening or no change in timing of the
terminal component would indicate block, whereas lengthening would indicate
persistent gap conduction. The results were compared with previously described
criteria for isthmus block. Ninety-two sites were assessed: 17 before and 75
after the achievement of complete isthmus block. The timing of the initial
component was delayed by 19+/-9 ms, and the terminal component was advanced by
13+/-8 ms after block and delayed by 12+/-9 ms in case of persisting conduction.
The sensitivity, specificity, and positive and negative predictive values for
linear block were 100%, 75%, 94%, and 100%, respectively. CONCLUSIONS: An
accurate assessment of isthmus block or persistent isthmus conduction is possible
with this technique of differential pacing.
PMID- 11004143
TI - Predicting outcome of defibrillation by spectral characterization and
nonparametric classification of ventricular fibrillation in patients with out-of
hospital cardiac arrest.
AB - BACKGROUND: In 156 patients with out-of-hospital cardiac arrest of cardiac cause,
we analyzed the ability of 4 spectral features of ventricular fibrillation before
a total of 868 shocks to discriminate or not between segments that correspond to
return of spontaneous circulation (ROSC). METHODS AND RESULTS: Centroid
frequency, peak power frequency, spectral flatness, and energy were studied. A
second decorrelated feature set was generated with the coefficients of the
principal component analysis transformation of the original feature set. Each
feature set was split into training and testing sets for improved reliability in
the evaluation of nonparametric classifiers for each possible feature
combination. The combination of centroid frequency and peak power frequency
achieved a mean+/-SD sensitivity of 92+/-2% and specificity of 27+/-2% in
testing. The highest performing classifier corresponded to the combination of the
2 dominant decorrelated spectral features with sensitivity and specificity equal
to 92+/-2% and 42+/-1% in testing or a positive predictive value of 0.15 and a
negative predictive value of 0.98. Using the highest performing classifier, 328
of 781 shocks not leading to ROSC would have been avoided, whereas 7 of 87 shocks
leading to ROSC would not have been administered. CONCLUSIONS: The ECG contained
information predictive of shock therapy. This could reduce the delivery of
unsuccessful shocks and thereby the duration of unnecessary "hands-off" intervals
during cardiopulmonary resuscitation. The low specificity and positive predictive
value indicate that other features should be added to improve performance.
PMID- 11004144
TI - Predictors of atrial fibrillation after conventional and beating heart coronary
surgery: A prospective, randomized study.
AB - BACKGROUND: Atrial fibrillation (AF) increases the morbidity of CABG. The
pathophysiology is uncertain, and its prevention remains suboptimal. This
prospective, randomized study was designed to define the role of cardiopulmonary
bypass (CPB) and cardioplegic arrest in the pathogenesis of this complication.
METHODS AND RESULTS: Two hundred patients were prospectively randomized to (1) on
pump conventional surgery [(100 patients, 79 men, mean age 63 (40 to 77) years)]
with normothermic CPB and cardioplegic arrest of the heart or (2) off-pump
surgery [(100 patients, 82 men, mean age 63 (38 to 86) years)] on the beating
heart. Heart rate and rhythm were continuously monitored with an automated
arrhythmia detector during the first 72 hours after surgery. Thereafter, routine
clinical observation was performed and continuous monitoring restarted in the
case of arrhythmia. The association of perioperative factors with AF was
investigated by univariate analysis. Significant variables were then included
into a stepwise logistic regression model to ascertain their independent
influence on the occurrence of AF. There were no significant baseline differences
between groups. Thirty-nine patients in the on-pump group and 8 patients in the
off-pump group had postoperative sustained AF (P:=0.001). Univariate analysis
showed that CPB inclusive of cardioplegic arrest, postoperative inotropic
support, intubation time, chest infection, and hospital length of stay were
predictors of AF (all P:<0.05). However, stepwise multivariate regression
analysis identified CPB inclusive of cardioplegic arrest as the only independent
predictor of postoperative AF (OR 7.4; CI 3.4 to 17.9). CONCLUSIONS: CPB
inclusive of cardioplegic arrest is the main independent predictor of
postoperative AF in patients undergoing coronary revascularization.
PMID- 11004145
TI - Relationship between circadian blood pressure patterns and progression of early
carotid atherosclerosis: A 3-year follow-up study.
AB - BACKGROUND: Arterial hypertension is a major risk factor for cardiovascular
damage. The results of several studies suggest that target organ damage is
greater in hypertensive persons with high blood pressure variability. METHODS AND
RESULTS: During 3.3 years of follow-up, we studied the relationship between
circadian blood pressure changes and the progression of early carotid
atherosclerosis in 286 patients aged >55 years. Blood pressure patterns were
evaluated with a long-term blood pressure monitor, and the extent of
atherosclerosis was measured as the intima-media wall thickness (IMT) of the
common carotid artery. Patients were subdivided according to blood pressure
variability. The progression of IMT was significantly greater in the patients
with increased systolic blood pressure variability (0.11 mm/y [95% CI 0.09 to
0.14] versus 0.05 mm/y [0.03 to 0.08]; P:<0.005) even after adjustment for other
risk factors. Multivariate regression analysis revealed the daytime systolic
blood pressure variability to be the best predictor for the progression of IMT.
Raised daytime systolic blood pressure variability (>15 mm Hg) is associated with
an increased relative risk of the development of early atherosclerosis (3.9 [1.4
to 11.1]; P:<0.01) and of cardiovascular events (1.87 [1.08 to 3.20]; P:<0.01).
CONCLUSIONS: The daytime systolic blood pressure variability is a strong
predictor of early carotid atherosclerosis progression and is useful to define
the risk-benefit ratio of therapeutic approaches.
PMID- 11004146
TI - Value of serum-soluble intercellular adhesion molecule-1 for the noninvasive risk
assessment of transplant coronary artery disease, posttransplant ischemic events,
and cardiac graft failure.
AB - BACKGROUND: Adhesion molecules on arterial endothelium have been implicated in
spontaneous atherosclerosis and transplant coronary artery disease (CAD). We
studied whether elevated serum-soluble intercellular adhesion molecule-1 (sICAM
1) during the immediate posttransplant period was a risk factor for CAD,
posttransplant ischemic events, or cardiac graft failure. METHODS AND RESULTS: We
initially studied serum sICAM-1 in a subset of 16 cardiac allograft recipients
(5.5+/-0.7 samples per patient) to determine a cutoff point that best correlated
with presence of arterial and arteriolar endothelial ICAM-1 in matching
endomyocardial biopsies. The cutoff value was 308 ng/mL. Subsequently, we
prospectively evaluated serum sICAM-1 in serial samples (5.3+/-0.1 per patient)
obtained during the first 3 months after transplantation in a validation subset
of 130 recipients and correlated early sICAM-1 levels with long-term outcome.
Serum sICAM-1 >308 ng/mL correlated significantly with ICAM-1 on arterial and
arteriolar endothelium (P:=0.02). Cardiac allograft recipients with serum sICAM-1
>308 ng/mL had 2.67 (95% CI, 1.28 to 5.59, P:=0.009) times greater risk of CAD
and 3.63 (95% CI, 1.05 to 12.5, P:=0.04) times greater risk of graft failure.
Recipients with sICAM-1 >308 ng/mL also developed more severe CAD (P:=0.009) and
more ischemic events (P:=0.03) after transplantation. CONCLUSIONS: Serum sICAM-1
levels can be used to noninvasively assess risk of transplant CAD, posttransplant
ischemic events, and cardiac graft failure.
PMID- 11004147
TI - Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor
blockade prevent cardiac remodeling in pigs after myocardial infarction: role of
tissue angiotensin II.
AB - BACKGROUND: The mechanisms behind the beneficial effects of renin-angiotensin
system blockade after myocardial infarction (MI) are not fully elucidated but may
include interference with tissue angiotensin II (Ang II). METHODS AND RESULTS:
Forty-nine pigs underwent coronary artery ligation or sham operation and were
studied up to 6 weeks. To determine coronary angiotensin I (Ang I) to Ang II
conversion and to distinguish plasma-derived Ang II from locally synthesized Ang
II, (125)I-labeled and endogenous Ang I and II were measured in plasma and in
infarcted and noninfarcted left ventricle (LV) during (125)I-Ang I infusion. Ang
II type 1 (AT(1)) receptor-mediated uptake of circulating (125)I-Ang II was
increased at 1 and 3 weeks in noninfarcted LV, and this uptake was the main cause
of the transient elevation in Ang II levels in the noninfarcted LV at 1 week. Ang
II levels and AT(1) receptor-mediated uptake of circulating Ang II were reduced
in the infarct area at all time points. Coronary Ang I to Ang II conversion was
unaffected by MI. Captopril and the AT(1) receptor antagonist eprosartan
attenuated postinfarct remodeling, although both drugs increased cardiac Ang II
production. Captopril blocked coronary conversion by >80% and normalized Ang II
uptake in the noninfarcted LV. Eprosartan did not affect coronary conversion and
blocked cardiac Ang II uptake by >90%. CONCLUSIONS: Both circulating and locally
generated Ang II contribute to remodeling after MI. The rise in tissue Ang II
production during angiotensin-converting enzyme inhibition and AT(1) receptor
blockade suggests that the antihypertrophic effects of these drugs result not
only from diminished AT(1) receptor stimulation but also from increased
stimulation of growth-inhibitory Ang II type 2 receptors.
PMID- 11004148
TI - Cardiomyocyte death induced by myocardial ischemia and reperfusion: measurement
with recombinant human annexin-V in a mouse model.
AB - INTRODUCTION: Phosphatidylserine (PS) externalization is regarded as one of the
earliest hallmarks of cells undergoing programmed cell death. We studied the use
of labeled human recombinant annexin-V, a protein selectively binding to PS, to
detect cardiomyocyte death in an in vivo mouse model of cardiac ischemia and
reperfusion (I/R). METHODS AND RESULTS: I/R was induced in mouse hearts by
ligation and subsequent release of a suture around the left anterior descending
coronary artery. Annexin-V (25 mg/kg) fused to a marker molecule was injected
intra-arterially 30 minutes before euthanasia. After 15 minutes of ischemia
followed by 30 minutes of reperfusion, 1.4+/-1. 2% (mean+/-SD) of the
cardiomyocytes in the area at risk were annexin-V positive (n=6). This increased
to 11.4+/-1.9% after 15 minutes of ischemia followed by 90 minutes of reperfusion
(n=7) and to 20.2+/-3.3% after 30 minutes of ischemia followed by 90 minutes of
reperfusion (n=7). In control mice, including those injected with annexin-V at
the binding site of PS, no annexin-V-positive cells were observed. DNA gel
electrophoresis showed typical laddering starting after 15 minutes of ischemia
followed by 30 minutes of reperfusion, suggesting activation of the cell death
program. Intervention in the cell death program by pretreatment with a novel
Na(+)-H(+) exchange inhibitor substantially decreased annexin-V-positive
cardiomyocytes from 20.2% to 2.2% in mice after 30 minutes of ischemia followed
by 90 minutes of reperfusion. CONCLUSIONS: These data suggest that labeled
annexin-V is useful for in situ detection of cell death in an in vivo model of
I/R in the heart and for the evaluation of cell death-blocking strategies.
PMID- 11004149
TI - Mechanisms of ventricular fibrillation induction by 60-Hz alternating current in
isolated swine right ventricle.
AB - BACKGROUND: The mechanisms by which 60-Hz alternating current (AC) can induce
ventricular fibrillation (VF) are unknown. METHODS AND RESULTS: We studied 7
isolated perfused swine right ventricles in vitro. The action potential duration
restitution curve was determined. Optical mapping techniques were used to
determine the patterns of activation on the epicardium during 5-second 60-Hz AC
stimulation (10 to 999 microA). AC captured the right ventricles at 100+/-65
microA, which is significantly lower than the direct current pacing threshold
(0.77+/-0.45 mA, P:<0.05). AC induced ventricular tachycardia or VF at 477+/-266
microA, when the stimulated responses to AC had (1) short activation CLs (128+/
14 ms), (2) short diastolic intervals (16+/-9 ms), and (3) short diastolic
intervals associated with a steep action potential duration restitution curve.
Optical mapping studies showed that during rapid ventricular stimulation by AC, a
wave front might encounter the refractory tail of an earlier wave front,
resulting in the formation of a wave break and VF. Computer simulations
reproduced these results. CONCLUSIONS: AC at strengths less than the regular
pacing threshold can capture the ventricle at fast rates. Accidental AC leak to
the ventricles could precipitate VF and sudden death if AC results in a fast
ventricular rate coupled with a steep restitution curve and a nonuniform recovery
of excitability of the myocardium.
PMID- 11004150
TI - Intrapericardial paclitaxel delivery inhibits neointimal proliferation and
promotes arterial enlargement after porcine coronary overstretch.
AB - BACKGROUND: Catheter-based intrapericardial (IPC) delivery of therapeutic agents
has recently been demonstrated. Paclitaxel is known to inhibit vascular smooth
muscle cell proliferation. This study examined the effect of IPC instillation of
paclitaxel on neointimal proliferation after balloon overstretch of porcine
coronary arteries. METHODS AND RESULTS: Overstretch injury of coronary arteries
was followed by IPC administration of micellar paclitaxel at low dose (LD, 10 mg;
n=6) or high dose (HD, 50 mg; n=7) or of control micelles (50 mg, n=5). Animals
were euthanized 28 days after balloon dilation. Arterial injury indices were no
different among the groups. The neointimal area, maximal intimal thickness, and
adventitial thickness were significantly reduced in both LD (0.47+/-0.04 mm(2),
0.43+/-0.03 mm, and 0.35+/-0.02 mm, respectively) and HD (0.51+/-0.06 mm(2),
0.42+/-0.03 mm, and 0. 38+/-0.03 mm, respectively) paclitaxel groups compared
with the control group (0.79+/-0.07 mm(2), 0.56+/-0.02 mm, and 0.47+/-0.02 mm,
respectively; P:<0.001). Meanwhile, the vessel circumference measured at the
external elastic lamina of paclitaxel-treated vessels was significantly larger
than the control circumference. Apoptotic cells were found in the neointima. The
apoptotic cell percentage was not different between the control (1.72%) and LD
(2. 31%) groups but was higher in the HD group (7.07%, P:<0.0001 versus control
and LD groups). Immunostaining for matrix metalloproteinase-2 revealed concurrent
reduction in the HD group compared with the control and LD groups. CONCLUSIONS:
IPC space delivery of a single dose of paclitaxel significantly reduces vessel
narrowing in this balloon-overstretch model. This effect is mediated by reduction
of neointimal mass as well as positive vascular remodeling.
PMID- 11004151
TI - Cardiac endothelin system impairs left ventricular function in renin-dependent
hypertension via decreased sarcoplasmic reticulum Ca(2+) uptake.
AB - BACKGROUND: We evaluated the role of the cardiac endothelin (ET) system in
compensated hypertensive left ventricular (LV) hypertrophy (LVH) and after the
transition toward LV dysfunction. METHODS AND RESULTS: Hypertensive transgenic
rats overexpressing the Ren2 gene (Ren2 rats) were investigated between the ages
of 10 and 30 weeks (Ren2-10 and Ren2-30 groups, respectively) and compared with
age-matched normotensive Sprague-Dawley (SD) rats (SD-10 and SD-30 groups,
respectively). Systolic blood pressure and LV weight were elevated in both Ren2
groups compared with their age-matched SD control groups (P:<0.0001). In Ren2-30
rats, LV end-diastolic pressure increased and -dP/dt(max) decreased compared with
the values in SD-30 and Ren2-10 rats (P:<0.05). This was paralleled by an
activation of LV mRNA expression of preproET-1 and ET-converting enzyme-1 and ET
subtype A (ETA) receptor binding in Ren2-30 compared with Ren2-10 rats
(P:<0.001). Cardiac fibrosis was increased and sarcoplasmic reticulum (SR) Ca(2+)
reuptake was reduced in Ren2-30 compared with SD-30 and Ren2-10 rats (P:<0.05).
Treatment of Ren2 rats with the selective ETA receptor antagonist Lu135252
between 10 and 30 weeks of age did not lower systolic blood pressure, heart
weight, or cardiac fibrosis but completely prevented the deterioration of LV end
diastolic pressure and abolished alterations in -dP/dt(max) and SR Ca(2+)
reuptake compared with no treatment in Ren2-30 and SD-30 rats (P:<0.05).
CONCLUSIONS: Activation of the cardiac ET system accounts at least in part for
the LV dysfunction that gradually develops in LVH. The protective effect of ETA
antagonism can be attributed to the improvement of diastolic LV function that is
due to normalization of impaired SR Ca(2+) uptake.
PMID- 11004152
TI - Coronary artery angiography using multislice computed tomography images.
PMID- 11004153
TI - Assessment of functional capacity in clinical and research applications: An
advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council
on Clinical Cardiology, American Heart Association.
PMID- 11004154
TI - Distal embolization: A threat to the coronary artery?
PMID- 11004155
TI - C-reactive protein and hormone replacement therapy.
PMID- 11004156
TI - Scared to death.
PMID- 11004157
TI - Decreased apoptosis and tissue factor expression after lipid lowering.
PMID- 11004158
TI - Dilated cardiomyopathy and the desmin gene.
PMID- 11004159
TI - Mitral valve aneurysm in endocarditis.
PMID- 11004160
TI - Keys to symbiotic harmony.
PMID- 11004161
TI - ssgA is essential for sporulation of Streptomyces coelicolor A3(2) and affects
hyphal development by stimulating septum formation.
AB - The role of ssgA in cell division and development of streptomycetes was analyzed.
An ssgA null mutant of Streptomyces coelicolor produced aerial hyphae but failed
to sporulate, and ssgA can therefore be regarded as a novel whi gene. In addition
to the morphological changes, antibiotic production was also disturbed, with
strongly reduced actinorhodin production. These defects could be complemented by
plasmid-borne ssgA. In the wild-type strain, transcription of ssgA was induced by
nutritional shift-down and was shown to be linked to that of the upstream-located
gene ssgR, which belongs to the family of iclR-type transcriptional regulator
genes. Analysis of mycelium harvested from liquid-grown cultures by transmission
electron microscopy showed that septum formation had strongly increased in ssgA
overexpressing strains in comparison to wild-type S. coelicolor and that spore
like compartments were produced at high frequency. Furthermore, the hyphae were
significantly wider and contained irregular and often extremely thick septa.
These data underline the important role for ssgA in Streptomyces cell division.
PMID- 11004162
TI - Effects of nonpolar mutations in each of the seven Bacillus subtilis mrp genes
suggest complex interactions among the gene products in support of Na(+) and
alkali but not cholate resistance.
AB - The Bacillus subtilis mrp (multiple resistance and pH) operon supports Na(+) and
alkali resistance via an Na(+)/H(+) antiport, as well as cholate efflux and
resistance. Among the individual mutants with nonpolar mutations in each of the
seven mrp genes, only the mrpF mutant exhibited cholate sensitivity and a cholate
efflux defect that were complemented by expression of the deleted gene in trans.
Expression of mrpF in the mrp null (VKN1) strain also restored cholate transport
and increased Na(+) efflux, indicating that MrpF does not require even low levels
of other mrp gene expression for its own function. In contrast to MrpF, MrpA
function had earlier seemed to depend upon at least modest expression of other
mrp genes, i.e., mrpA restored Na(+) resistance and efflux to strain VK6 (a polar
mrpA mutant which expresses low levels of mrpB to -G) but not to the null strain
VKN1. In a wild-type background, each nonpolar mutation in individual mrp genes
caused profound Na(+) sensitivity at both pH 7.0 and 8.3. The mrpA and mrpD
mutants were particularly sensitive to alkaline pH even without added Na(+).
While transport assays in membrane vesicles from selected strains indicated that
MrpA-dependent antiport can occur by a secondary, proton motive force-dependent
mechanism, the requirement for multiple mrp gene products suggests that there are
features of energization, function, or stabilization that differ from typical
secondary membrane transporters. Northern analyses indicated regulatory
relationships among mrp genes as well. All the mrp mutants, especially the mrpA,
B, -D, -E, and -G mutants, had elevated levels of mrp RNA relative to the wild
type. Expression of an upstream gene, maeN, that encodes an Na(+)/malate
symporter, was coordinately regulated with mrp, although it is not part of the
operon.
PMID- 11004163
TI - Covariance of complementary rRNA loop nucleotides does not necessarily represent
functional pseudoknot formation in vivo.
AB - We examined mutationally a two-hairpin structure (nucleotides 57 to 70 and 76 to
110) in a region of domain I of Escherichia coli 23S rRNA that has been
implicated in specific functions in protein synthesis by other studies. On the
basis of the observed covariance of several nucleotides in each loop in Bacteria,
Archaea, and chloroplasts, the two hairpins have been proposed to form a
pseudoknot. Here, appropriate loop changes were introduced in vitro by site
directed mutagenesis to eliminate any possibility of base pairing between the
loops. The bacterial cells containing each cloned mutant rRNA operon were then
examined for cell growth, termination codon readthrough, and assembly of the
mutant rRNAs into functional ribosomes. The results show that, under the
conditions examined, the two hairpins do not form a pseudoknot structure that is
required for the functioning of the ribosome in vivo and therefore that sequence
covariance does not necessarily indicate the formation of a functional
pseudoknot.
PMID- 11004164
TI - Synergistic hydrolysis of carboxymethyl cellulose and acid-swollen cellulose by
two endoglucanases (CelZ and CelY) from Erwinia chrysanthemi.
AB - Erwinia chrysanthemi produces a battery of hydrolases and lyases which are very
effective in the maceration of plant cell walls. Although two endoglucanases
(CelZ and CelY; formerly EGZ and EGY) are produced, CelZ represents approximately
95% of the total carboxymethyl cellulase activity. In this study, we have
examined the effectiveness of CelY and CelZ alone and of combinations of both
enzymes using carboxymethyl cellulose (CMC) and amorphous cellulose (acid-swollen
cellulose) as substrates. Synergy was observed with both substrates. Maximal
synergy (1.8-fold) was observed for combinations containing primarily CelZ; the
ratio of enzyme activities produced was similar to those produced by cultures of
E. chrysanthemi. CelY and CelZ were quite different in substrate preference. CelY
was unable to hydrolyze soluble cellooligosaccharides (cellotetraose and
cellopentaose) but hydrolyzed CMC to fragments averaging 10.7 glucosyl units. In
contrast, CelZ readily hydrolyzed cellotetraose, cellopentaose, and amorphous
cellulose to produce cellobiose and cellotriose as dominant products. CelZ
hydrolyzed CMC to fragments averaging 3.6 glucosyl units. In combination, CelZ
and CelY hydrolyzed CMC to products averaging 2.3 glucosyl units. Synergy did not
require the simultaneous presence of both enzymes. Enzymatic modification of the
substrate by CelY increased the rate and extent of hydrolysis by CelZ. Full
synergy was retained by the sequential hydrolysis of CMC, provided CelY was used
as the first enzyme. A general mechanism is proposed to explain the synergy
between these two enzymes based primarily on differences in substrate preference.
PMID- 11004165
TI - Transcriptional regulation of the cpr gene cluster in ortho-chlorophenol
respiring Desulfitobacterium dehalogenans.
AB - To characterize the expression and possible regulation of reductive
dehalogenation in halorespiring bacteria, a 11.5-kb genomic fragment containing
the o-chlorophenol reductive dehalogenase-encoding cprBA genes of the gram
positive bacterium Desulfitobacterium dehalogenans was subjected to detailed
molecular characterization. Sequence analysis revealed the presence of eight
designated genes with the order cprTKZEBACD and with the same polarity except for
cprT. The deduced cprC and cprK gene products belong to the NirI/NosR and CRP-FNR
families of transcription regulatory proteins, respectively. CprD and CprE are
predicted to be molecular chaperones of the GroEL type, whereas cprT may encode a
homologue of the trigger factor folding catalysts. Northern blot analysis,
reverse transcriptase PCR, and primer extension analysis were used to elucidate
the transcriptional organization and regulation of the cpr gene cluster. Results
indicated halorespiration-specific transcriptional induction of the monocistronic
cprT gene and the biscistronic cprBA and cprZE genes. Occasional read-through at
cprC gives rise to a tetracistronic cprBACD transcript. Transcription of cprBA
was induced 15-fold upon addition of the o-chlorophenolic substrate 3-chloro-4
hydroxyphenylacetic acid within 30 min with concomitant induction of
dehalogenation activity. Putative regulatory protein binding motifs that to some
extent resemble the FNR box were identified in the cprT-cprK and cprK-cprZ
intergenic regions and the promoter at cprB, suggesting a role for FNR-like CprK
in the control of expression of the cprTKZEBACD genes.
PMID- 11004166
TI - Isolation of regulated genes of the cyanobacterium Synechocystis sp. strain PCC
6803 by differential display.
AB - Global identification of differentially regulated genes in prokaryotes is
constrained because the mRNA does not have a 3' polyadenylation extension; this
precludes specific separation of mRNA from rRNA and tRNA and synthesis of cDNAs
from the entire mRNA population. Knowledge of the entire genome sequence of
Synechocystis sp. strain PCC 6803 has enabled us to develop a differential
display procedure that takes advantage of a short palindromic sequence that is
dispersed throughout the Synechocystis sp. strain PCC 6803 genome. This sequence,
designated the HIP (highly iterated palindrome) element, occurs in approximately
half of the Synechocystis sp. strain PCC 6803 genes but is absent in rRNA and
tRNA genes. To determine the feasibility of exploiting the HIP element, alone or
in combination with specific primer subsets, for analyzing differential gene
expression, we used HIP-based primers to identify light intensity-regulated
genes. Several gene fragments, including those encoding ribosomal proteins and
phycobiliprotein subunits, were differentially amplified from RNA templates
derived from cells grown in low light or exposed to high light for 3 h. One novel
finding was that expression of certain genes of the pho regulon, which are under
the control of environmental phosphate levels, were markedly elevated in high
light. High-light activation of pho regulon genes correlated with elevated growth
rates that occur when the cells are transferred from low to high light. These
results suggest that in high light, the rate of growth of Synechocystis sp.
strain PCC 6803 exceeds its capacity to assimilate phosphate, which, in turn, may
trigger a phosphate starvation response and activation of the pho regulon.
PMID- 11004167
TI - The LE1 bacteriophage replicates as a plasmid within Leptospira biflexa:
construction of an L. biflexa-Escherichia coli shuttle vector.
AB - We have discovered that LE1, one of the plaque-forming phages previously
described as lytic for the Leptospira biflexa saprophytic spirochete (I. Saint
Girons, D. Margarita, P. Amouriaux, and G. Baranton, Res. Microbiol. 141:1131
1138, 1990), was indeed temperate. LE1 was found to be unusual, as Southern blot
analysis indicated that it is one of the few phages to replicate in the prophage
state as a circular plasmid. The unavailability of such small endogenous
replicons has hindered genetic experimentation in Leptospira. We have developed a
shuttle vector with DNA derived from LE1. Random LE1 DNA fragments were cloned
into a pGEM 7Zf(+) derivative devoid of most of the bla gene but carrying a
kanamycin resistance marker from the gram-positive bacterium Enterococcus
(Streptococcus) faecalis. These constructs were transformed into L. biflexa
strain Patoc 1 by electroporation, giving rise to kanamycin-resistant
transformants. A 2.2-kb fragment from LE1 was responsible for replication of the
vector in L. biflexa. However, a larger region including an intact parA gene
homologue was necessary for the stability of the shuttle vector. Direct repeats
and AT-rich regions characterized the LE1 origin of replication. Our data
indicate that the replicon derived from the LE1 leptophage, together with the
kanamycin resistance gene, is a promising tool with which to develop the genetics
of Leptospira species.
PMID- 11004168
TI - Role of the Escherichia coli nucleotide excision repair proteins in DNA
replication.
AB - DNA polymerase I (PolI) functions both in nucleotide excision repair (NER) and in
the processing of Okazaki fragments that are generated on the lagging strand
during DNA replication. Escherichia coli cells completely lacking the PolI enzyme
are viable as long as they are grown on minimal medium. Here we show that
viability is fully dependent on the presence of functional UvrA, UvrB, and UvrD
(helicase II) proteins but does not require UvrC. In contrast, delta polA cells
grow even better when the uvrC gene has been deleted. Apparently UvrA, UvrB, and
UvrD are needed in a replication backup system that replaces the PolI function,
and UvrC interferes with this alternative replication pathway. With specific
mutants of UvrC we could show that the inhibitory effect of this protein is
related to its catalytic activity that on damaged DNA is responsible for the 3'
incision reaction. Specific mutants of UvrA and UvrB were also studied for their
capacity to support the PolI-independent replication. Deletion of the UvrC
binding domain of UvrB resulted in a phenotype similar to that caused by deletion
of the uvrC gene, showing that the inhibitory incision activity of UvrC is
mediated via binding to UvrB. A mutation in the N-terminal zinc finger domain of
UvrA does not affect NER in vivo or in vitro. The same mutation, however, does
give inviability in combination with the delta polA mutation. Apparently the N
terminal zinc-binding domain of UvrA has specifically evolved for a function
outside DNA repair. A model for the function of the UvrA, UvrB, and UvrD proteins
in the alternative replication pathway is discussed.
PMID- 11004169
TI - glnE is an essential gene in Mycobacterium tuberculosis.
AB - Mycobacterium tuberculosis possesses a homologue of glnE, potentially encoding a
regulator of glutamine synthetase activity. We attempted to construct glnE
disrupted mutants using a two-step strategy, whereby a single-crossover strain
was first isolated, followed by sacB counterselection to isolate the double
crossover strain. Of 192 sucrose-resistant colonies tested, none were mutants,
although the wild-type double crossover could be easily isolated. When a second
copy of the wild-type glnE was integrated into the chromosome, we could isolate
both wild-type and mutant double-crossover strains. Thus, the chromosomal gene
could only be replaced with a disrupted copy when another functional copy of the
gene was provided, demonstrating that this gene is essential under the conditions
tested.
PMID- 11004170
TI - Population studies of methicillin-resistant and -sensitive Staphylococcus aureus
strains reveal a lack of variability in the agrD gene, encoding a staphylococcal
autoinducer peptide.
AB - The virulence of Staphylococcus aureus is controlled by the accessory gene
regulator (agr) system, including an extracellular inducer encoded by agrD.
Variable agr PCR restriction fragment length polymorphism (RFLP) patterns of
unique S. aureus strains (n = 192) were determined for a region comprising agrD
and parts of the neighboring agrC and agrB genes. Twelve unique RFLP patterns
were identified among S. aureus strains in general; these patterns were further
specified by sequencing. All sequences could be catalogued in the three current
agr groups. A major proportion of the S. aureus strains belong to agr group 1,
whereas only 6% of the methicillin-susceptible S. aureus strains and 5% of the
methicillin-resistant S. aureus strains belong to agr groups 2 and 3,
respectively. The homology between groups varied from 75 to 80%, and within
groups it varied from 96 to 100%. Different levels of sequence variability were
observed in the different agr genes. agr-related bacterial interference among
colonizing S. aureus strains in the noses of persistent and intermittent human
carriers was studied. S. aureus strains belonging to different agr groups were
encountered in the same individual. This may suggest that the activity of the
agrD gene product does not define colonization dynamics, which is further
substantiated by the rarity of agr group 2 and 3 strains.
PMID- 11004171
TI - A single-transformation gene function test in diploid Candida albicans.
AB - The fungal pathogen Candida albicans is naturally diploid, and current gene
disruption strategies require two successive transformations. We describe here a
genetic construct (UAU1) for which two copies may be selected. Insertion of UAU1
into one genomic site, after a single transformation, allows selection for
segregants with two copies of the insertion. Major classes of segregants are
those carrying homozygous insertion mutations and allelic triplications, which
have two insertion alleles and a wild-type allele. Thus nonessential and
essential genes may be distinguished rapidly through PCR tests for homozygosis
and triplication. We find that homozygous mutations may be isolated at three
nonessential loci (ADE2, RIM20, and YGR189), while only allelic triplications
were found at two essential loci (SNF1 and CDC28). We have unexpectedly isolated
homozygous mutants with mutations at CDC25; they are viable but defective in
filamentation on serum-containing medium. The UAU1 cassette is thus useful to
assess rapidly the essentiality of C. albicans genes.
PMID- 11004172
TI - Characterization and expression of HmuR, a TonB-dependent hemoglobin receptor of
Porphyromonas gingivalis.
AB - The gram-negative pathogen Porphyromonas gingivalis requires hemin for growth.
Hemoglobin bound to haptoglobin and hemin complexed to hemopexin can be used as
heme sources, indicating that P. gingivalis must have a means to remove the hemin
from these host iron-binding proteins. However, the specific mechanisms utilized
by P. gingivalis for the extraction of heme from heme-binding proteins and for
iron transport are poorly understood. In this study we have determined that a
newly identified TonB-dependent hemoglobin-hemin receptor (HmuR) is involved in
hemoglobin binding and utilization in P. gingivalis A7436. HmuR shares amino acid
homology with TonB-dependent outer membrane receptors of gram-negative bacteria
involved in the acquisition of iron from hemin and hemoglobin, including HemR of
Yersinia enterocolitica, ShuA of Shigella dysenteriae, HpuB of Neisseria
gonorrhoeae and N. meningitidis, HmbR of N. meningitidis, HgbA of Haemophilus
ducreyi, and HgpB of H. influenzae. Southern blot analysis confirmed the presence
of the hmuR gene and revealed genetic variability in the carboxy terminus of hmuR
in P. gingivalis strains 33277, 381, W50, and 53977. We also identified directly
upstream of the hmuR gene a gene which we designated hmuY. Upstream of the hmuY
start codon, a region with homology to the Fur binding consensus sequence was
identified. Reverse transcription-PCR analysis revealed that hmuR and hmuY were
cotranscribed and that transcription was negatively regulated by iron.
Inactivation of hmuR resulted in a decreased ability of P. gingivalis to bind
hemoglobin and to grow with hemoglobin or hemin as sole iron sources. Escherichia
coli cells expressing recombinant HmuR were shown to bind hemoglobin and hemin.
Furthermore, purified recombinant HmuR was demonstrated to bind hemoglobin. Taken
together, these results indicate that HmuR serves as the major TonB-dependent
outer membrane receptor involved in the utilization of both hemin and hemoglobin
in P. gingivalis.
PMID- 11004173
TI - Identification of RpoS (sigma(S))-regulated genes in Salmonella enterica serovar
typhimurium.
AB - The rpoS gene encodes the alternative sigma factor sigma(S) (RpoS) and is
required for survival of bacteria under starvation and stress conditions. It is
also essential for Salmonella virulence in mice. Most work on the RpoS regulon
has been in the closely related enterobacterial species Escherichia coli. To
characterize the RpoS regulon in Salmonella, we isolated 38 unique RpoS-activated
lacZ gene fusions from a bank of Salmonella enterica serovar Typhimurium mutants
harboring random Tn5B21 mutations. Dependence on RpoS varied from 3-fold to over
95-fold, and all gene fusions isolated were regulated by growth phase. The
identities of 21 RpoS-dependent fusions were determined by DNA sequence analysis.
Seven of the fusions mapped to DNA regions in Salmonella serovar Typhimurium that
do not match any known E. coli sequence, suggesting that the composition of the
RpoS regulon differs markedly in the two species. The other 14 fusions mapped to
13 DNA regions very similar to E. coli sequences. None of the insertion mutations
in DNA regions common to both species appeared to affect Salmonella virulence in
BALB/c mice. Of these, only three (otsA, katE, and poxB) are located in known
members of the RpoS regulon. Ten insertions mapped in nine open reading frames of
unknown function (yciF, yehY, yhjY, yncC, yjgB, yahO, ygaU, ycgB, and yeaG)
appear to be novel members of the RpoS regulon. One insertion, that in mutant
C52::H87, was in the noncoding region upstream from ogt, encoding a O(6)
methylguanine DNA methyltransferase involved in repairing alkylation damage in
DNA. The ogt coding sequence is very similar to the E. coli homolog, but the ogt
5' flanking regions were found to be markedly different in the two species,
suggesting genetic rearrangements. Using primer extension assays, a specific ogt
mRNA start site was detected in RNAs of the Salmonella serovar Typhimurium wild
type strains C52 and SL1344 but not in RNAs of the mutant strains C52K (rpoS),
SL1344K (rpoS), and C52::H87. In mutant C52::H87, Tn5B21 is inserted at the ogt
mRNA start site, with lacZ presumably transcribed from the identified RpoS
regulated promoter. These results indicate that ogt gene expression in Salmonella
is regulated by RpoS in stationary phase of growth in rich medium, a finding that
suggests a novel role for RpoS in DNA repair functions.
PMID- 11004175
TI - A truncated soluble Bacillus signal peptidase produced in Escherichia coli is
subject to self-cleavage at its active site.
AB - Soluble forms of Bacillus signal peptidases which lack their unique amino
terminal membrane anchor are prone to degradation, which precludes their high
level production in the cytoplasm of Escherichia coli. Here, we show that the
degradation of soluble forms of the Bacillus signal peptidase SipS is largely due
to self-cleavage. First, catalytically inactive soluble forms of this signal
peptidase were not prone to degradation; in fact, these mutant proteins were
produced at very high levels in E. coli. Second, the purified active soluble form
of SipS displayed self-cleavage in vitro. Third, as determined by N-terminal
sequencing, at least one of the sites of self-cleavage (between Ser15 and Met16
of the truncated enzyme) strongly resembles a typical signal peptidase cleavage
site. Self-cleavage at the latter position results in complete inactivation of
the enzyme, as Ser15 forms a catalytic dyad with Lys55. Ironically, self-cleavage
between Ser15 and Met16 cannot be prevented by mutagenesis of Gly13 and Ser15,
which conform to the -1, -3 rule for signal peptidase recognition, because these
residues are critical for signal peptidase activity.
PMID- 11004174
TI - Transport of C(4)-dicarboxylates in Wolinella succinogenes.
AB - C(4)-dicarboxylate transport is a prerequisite for anaerobic respiration with
fumarate in Wolinella succinogenes, since the substrate site of fumarate
reductase is oriented towards the cytoplasmic side of the membrane. W.
succinogenes was found to transport C(4)-dicarboxylates (fumarate, succinate,
malate, and aspartate) across the cytoplasmic membrane by antiport and uniport
mechanisms. The electrogenic uniport resulted in dicarboxylate accumulation
driven by anaerobic respiration. The molar ratio of internal to external
dicarboxylate concentration was up to 10(3). The dicarboxylate antiport was
either electrogenic or electroneutral. The electroneutral antiport required the
presence of internal Na(+), whereas the electrogenic antiport also operated in
the absence of Na(+). In the absence of Na(+), no electrochemical proton
potential (delta p) was measured across the membrane of cells catalyzing fumarate
respiration. This suggests that the proton potential generated by fumarate
respiration is dissipated by the concomitant electrogenic dicarboxylate antiport.
Three gene loci (dcuA, dcuB, and dctPQM) encoding putative C(4)-dicarboxylate
transporters were identified on the genome of W. succinogenes. The predicted gene
products of dcuA and dcuB are similar to the Dcu transporters that are involved
in the fumarate respiration of Escherichia coli with external C(4)
dicarboxylates. The genes dctP, -Q, and -M probably encode a binding-protein
dependent secondary uptake transporter for dicarboxylates. A mutant (DcuA(-)
DcuB(-)) of W. succinogenes lacking the intact dcuA and dcuB genes grew by
nitrate respiration with succinate as the carbon source but did not grow by
fumarate respiration with fumarate, malate, or aspartate as substrates. The DcuA(
), DcuB(-), and DctQM(-) mutants grew by fumarate respiration as well as by
nitrate respiration with succinate as the carbon source. Cells of the DcuA(-)
DcuB(-) mutant performed fumarate respiration without generating a proton
potential even in the presence of Na(+). This explains why the DcuA(-) DcuB(-)
mutant does not grow by fumarate respiration. Growth by fumarate respiration
appears to depend on the function of the Na(+)-dependent, electroneutral
dicarboxylate antiport which is catalyzed exclusively by the Dcu transporters.
Dicarboxylate transport via the electrogenic uniport is probably catalyzed by the
DctPQM transporter and by a fourth, unknown transporter that may also operate as
an electrogenic antiporter.
PMID- 11004176
TI - Polyprenyl phosphate biosynthesis in Mycobacterium tuberculosis and Mycobacterium
smegmatis.
AB - Mycobacterium smegmatis has been shown to contain two forms of polyprenyl
phosphate (Pol-P), while Mycobacterium tuberculosis contains only one. Utilizing
subcellular fractions from M. smegmatis and M. tuberculosis, we show that Pol-P
synthesis is different in these species. The specific activities of the prenyl
diphosphate synthases in M. tuberculosis are 10- to 100-fold lower than those in
M. smegmatis. In M. smegmatis decaprenyl diphosphate and heptaprenyl diphosphate
were the main products synthesized in vitro, whereas in M. tuberculosis only
decaprenyl diphosphate was synthesized. The data from both organisms suggest that
geranyl diphosphate is the allylic substrate for two distinct prenyl diphosphate
synthases, one located in the cell membrane that synthesizes omega,E,Z-farnesyl
diphosphate and the other present in the cytosol that synthesizes omega,E,E,E
geranylgeranyl diphosphate. In M. smegmatis, the omega,E, Z-farnesyl diphosphate
is utilized by a membrane-associated prenyl diphosphate synthase activity to
generate decaprenyl diphosphate, and the omega,E,E,E-geranylgeranyl diphosphate
is utilized by a membrane-associated activity for the synthesis of the
heptaprenyl diphosphate. In M. tuberculosis, however, omega,E,E,E-geranylgeranyl
diphosphate is not utilized for the synthesis of heptaprenyl diphosphate. Thus,
the difference in the compositions of the Pol-P of M. smegmatis and M.
tuberculosis can be attributed to distinct enzymatic differences between these
two organisms.
PMID- 11004177
TI - The torYZ (yecK bisZ) operon encodes a third respiratory trimethylamine N-oxide
reductase in Escherichia coli.
AB - The bisZ gene of Escherichia coli was previously described as encoding a minor
biotin sulfoxide (BSO) reductase in addition to the main cytoplasmic BSO
reductase, BisC. In this study, bisZ has been renamed torZ based on the findings
that (i) the torZ gene product, TorZ, is able to reduce trimethylamine N-oxide
(TMAO) more efficiently than BSO; (ii) although TorZ is more homologous to BisC
than to the TMAO reductase TorA (63 and 42% identity, respectively), it is
located mainly in the periplasm as is TorA; (iii) torZ belongs to the torYZ
operon, and the first gene, torY (formerly yecK), encodes a pentahemic c-type
cytochrome homologous to the TorC cytochrome of the TorCAD respiratory system.
Furthermore, the torYZ operon encodes a third TMAO respiratory system, with
catalytic properties that are clearly different from those of the TorCAD and the
DmsABC systems. The torYZ and the torCAD operons may have diverged from a common
ancestor, but, surprisingly, no torD homologue is found in the sequences around
torYZ. Moreover, the torYZ operon is expressed at very low levels under the
conditions tested, and, in contrast to torCAD, it is not induced by TMAO or
dimethyl sulfoxide.
PMID- 11004178
TI - sigma(54) Promoters control expression of genes encoding the hook and basal body
complex in Rhodobacter sphaeroides.
AB - Gene expression of the flagellar system is tightly controlled by external stimuli
or intracellular signals. A general picture of this regulation has been obtained
from studies of Salmonella enterica serovar Typhimurium. However, these
regulatory mechanisms do not apply to all bacterial groups. In this study, we
have investigated regulation of the flagellar genetic system in Rhodobacter
sphaeroides. Deletion analysis, site-directed mutagenesis, and 5'-end mapping
were conducted in order to identify the fliO promoter. Our results indicate that
this promoter is recognized by the factor sigma(54). Additionally, 5'-end mapping
of the flgB and fliK transcripts suggests that these mRNAs are also transcribed
from sigma(54) promoters. Finally, we showed evidence that suggests that fliC
transcription is not entirely dependent on the presence of a complete basal body
hook structure. Our results are discussed in the context of a possible regulatory
hierarchy controlling flagellar gene expression in R. sphaeroides.
PMID- 11004179
TI - Myxococcus xanthus dif genes are required for biogenesis of cell surface fibrils
essential for social gliding motility.
AB - Myxococcus xanthus social (S) gliding motility has been previously reported by us
to require the chemotaxis homologues encoded by the dif genes. In addition, two
cell surface structures, type IV pili and extracellular matrix fibrils, are also
critical to M. xanthus S motility. We have demonstrated here that M. xanthus dif
genes are required for the biogenesis of fibrils but not for that of type IV
pili. Furthermore, the developmental defects of dif mutants can be partially
rescued by the addition of isolated fibril materials. Along with the chemotaxis
genes of various swarming bacteria and the pilGHIJ genes of the twitching
bacterium Pseudomonas aeruginosa, the M. xanthus dif genes belong to a unique
class of bacterial chemotaxis genes or homologues implicated in the biogenesis of
structures required for bacterial surface locomotion. Genetic studies indicate
that the dif genes are linked to the M. xanthus dsp region, a locus known to be
crucial for M. xanthus fibril biogenesis and S gliding.
PMID- 11004180
TI - Characterization of the ccpA gene of Enterococcus faecalis: identification of
starvation-inducible proteins regulated by ccpA.
AB - Inactivation of ccpA in Enterococcus faecalis leads to reduction of the growth
rate, derepression of the galKETR operon in the presence of a mixture of glucose
and galactose, and reduction of transcription of ldh in the presence of glucose.
Moreover, the E. faecalis ccpA gene fully complements a Bacillus subtilis ccpA
mutant, arguing for similar functions of these two homologous proteins. Protein
comparison on two-dimensional gels from the wild-type cells and the ccpA mutant
cells revealed a pleiotropic effect of the mutation on gene expression. The HPr
protein of the carbohydrate-phosphotransferase system was identified by
microsequencing, and a modification of its phosphorylation state was observed
between the wild-type and the mutant strains. Moreover, at least 16 polypeptides
are overexpressed in the mutant, and 6 are repressed. Interestingly, 13 of the 16
polypeptides whose synthesis is enhanced in the mutant were also identified as
glucose starvation proteins. The N-terminal amino acid sequences of four of them
match sequences deduced from genes coding for L-serine dehydratase,
dihydroxyacetone kinase (two genes), and a protein of unknown function from
Deinococcus radiodurans.
PMID- 11004181
TI - Characterization of bacteriophage lambda excisionase mutants defective in DNA
binding.
AB - The bacteriophage lambda excisionase (Xis) is a sequence-specific DNA binding
protein required for excisive recombination. Xis binds cooperatively to two DNA
sites arranged as direct repeats on the phage DNA. Efficient excision is achieved
through a cooperative interaction between Xis and the host-encoded factor for
inversion stimulation as well as a cooperative interaction between Xis and
integrase. The secondary structure of the Xis protein was predicted to contain a
typical amphipathic helix that spans residues 18 to 28. Several mutants,
defective in promoting excision in vivo, were isolated with mutations at
positions encoding polar amino acids in the putative helix (T. E. Numrych, R. I.
Gumport, and J. F. Gardner, EMBO J. 11:3797-3806, 1992). We substituted alanines
for the polar amino acids in this region. Mutant proteins with substitutions for
polar amino acids in the amino-terminal region of the putative helix exhibited
decreased excision in vivo and were defective in DNA binding. In addition, an
alanine substitution at glutamic acid 40 also resulted in altered DNA binding.
This indicates that the hydrophilic face of the alpha-helix and the region
containing glutamic acid 40 may form the DNA binding surfaces of the Xis protein.
PMID- 11004182
TI - The nrfA and nirB nitrite reductase operons in Escherichia coli are expressed
differently in response to nitrate than to nitrite.
AB - Escherichia coli possesses two distinct nitrite reductase enzymes encoded by the
nrfA and nirB operons. The expression of each operon is induced during anaerobic
cell growth conditions and is further modulated by the presence of either nitrite
or nitrate in the cells' environment. To examine how each operon is expressed at
low, intermediate, and high levels of either nitrate or nitrite, anaerobic
chemostat culture techniques were employed using nrfA-lacZ and nirB-lacZ reporter
fusions. Steady-state gene expression studies revealed a differential pattern of
nitrite reductase gene expression where optimal nrfA-lacZ expression occurred
only at low to intermediate levels of nitrate and where nirB-lacZ expression was
induced only by high nitrate conditions. Under these conditions, the presence of
high levels of nitrate suppressed nrfA gene expression. While either NarL or NarP
was able to induce nrfA-lacZ expression in response to low levels of nitrate,
only NarL could repress at high nitrate levels. The different expression profile
for the alternative nitrite reductase operon encoded by nirBDC under high-nitrate
conditions was due to transcriptional activation by either NarL or NarP. Neither
response regulator could repress nirB expression. Nitrite was also an inducer of
nirB and nrfA gene expression, but nitrate was always the more potent inducer by
>100-fold. Lastly, since nrfA operon expression is only induced under low-nitrate
concentrations, the NrfA enzyme is predicted to have a physiological role only
where nitrate (or nitrite) is limiting in the cell environment. In contrast, the
nirB nitrite reductase is optimally synthesized only when nitrate or nitrite is
in excess of the cell's capacity to consume it. Revised regulatory schemes are
presented for NarL and NarP in control of the two operons.
PMID- 11004183
TI - The N-terminal region of the Oenococcus oeni bacteriophage fOg44 lysin behaves as
a bona fide signal peptide in Escherichia coli and as a cis-inhibitory element,
preventing lytic activity on oenococcal cells.
AB - The function of the N-terminal region of the Oenococcus oeni phage fOg44 lysin
(Lys44) as an export signal was investigated. We observed that when induced in
Escherichia coli, Lys44 was cleaved between residues 27 and 28 in a SecA
dependent manner. Lys44 processing could be blocked by a specific signal
peptidase inhibitor and was severely reduced by modification of the cleavage
site. The lethal effect of Lys44 expression observed in E. coli was ascribed to
the presence of its N-terminal 27-residue sequence, as its deletion resulted in
the production of a nontoxic, albeit active, product. We have further established
that lytic activity in oenococcal cells was dependent on Lys44 processing. An
active protein with the molecular mass expected for the cleaved enzyme was
detected in extracts from O. oeni-infected cells. The temporal pattern of its
appearance suggests that synthesis and export of Lys44 in the infected host
progress along with phage maturation. Overall, these results provide, for the
first time, experimental evidence for the presence of a signal peptide in a
bacteriophage lysin. Database searches and alignment of protein sequences support
the prediction that other known O. oeni and Lactococcus lactis phages also encode
secretory lysins. The evolutionary significance of a putative phage lysis
mechanism relying on secretory lytic enzymes is tentatively discussed, on the
basis of host cell wall structure and autolytic capacity.
PMID- 11004184
TI - Leafy gall formation is controlled by fasR, an AraC-type regulatory gene in
Rhodococcus fascians.
AB - Rhodococcus fascians can interact with many plant species and induce the
formation of either leafy galls or fasciations. To provoke symptoms, R. fascians
strain D188 requires pathogenicity genes that are located on a linear plasmid,
pFiD188. The fas genes are essential for virulence and constitute an operon that
encodes, among other functions, a cytokinin synthase gene. Expression of the fas
genes is induced by extracts of infected plant tissue only. We have isolated an
AraC-type regulatory gene, fasR, located on pFiD188, which is indispensable for
pathogenesis and for fas gene expression. The combined results of our experiments
show that in vitro expression of the fas genes in a defined medium is strictly
regulated and that several environmental factors (pH, carbon and nitrogen
sources, phosphate and oxygen content, and cell density) and regulatory proteins
are involved. We further show that expression of the fas genes is controlled at
both the transcriptional and the translational levels. The complex expression
pattern probably reflects the necessity of integrating a multitude of signals and
underlines the importance of the fas operon in the pathogenicity of R. fascians.
PMID- 11004185
TI - Evidence of a role for LytB in the nonmevalonate pathway of isoprenoid
biosynthesis.
AB - It is proposed that the lytB gene encodes an enzyme of the deoxyxylulose-5
phosphate (DOXP) pathway that catalyzes a step at or subsequent to the point at
which the pathway branches to form isopentenyl diphosphate (IPP) and
dimethylallyl diphosphate (DMAPP). A mutant of the cyanobacterium Synechocystis
strain PCC 6803 with an insertion in the promoter region of lytB grew slowly and
produced greenish-yellow, easily bleached colonies. Insertions in the coding
region of lytB were lethal. Supplementation of the culture medium with the
alcohol analogues of IPP and DMAPP (3-methyl-3-buten-1-ol and 3-methyl-2-buten-1
ol) completely alleviated the growth impairment of the mutant. The Synechocystis
lytB gene and a lytB cDNA from the flowering plant Adonis aestivalis were each
found to significantly enhance accumulation of carotenoids in Escherichia coli
engineered to produce these colored isoprenoid compounds. When combined with a
cDNA encoding deoxyxylulose-5-phosphate synthase (dxs), the initial enzyme of the
DOXP pathway, the individual salutary effects of lytB and dxs were multiplied. In
contrast, the combination of lytB and a cDNA encoding IPP isomerase (ipi) was no
more effective in enhancing carotenoid accumulation than ipi alone, indicating
that the ratio of IPP and DMAPP produced via the DOXP pathway is influenced by
LytB.
PMID- 11004186
TI - Genes involved in anaerobic metabolism of phenol in the bacterium Thauera
aromatica.
AB - Genes involved in the anaerobic metabolism of phenol in the denitrifying
bacterium Thauera aromatica have been studied. The first two committed steps in
this metabolism appear to be phosphorylation of phenol to phenylphosphate by an
unknown phosphoryl donor ("phenylphosphate synthase") and subsequent
carboxylation of phenylphosphate to 4-hydroxybenzoate under release of phosphate
("phenylphosphate carboxylase"). Both enzyme activities are strictly phenol
induced. Two-dimensional gel electrophoresis allowed identification of several
phenol-induced proteins. Based on N-terminal and internal amino acid sequences of
such proteins, degenerate oligonucleotides were designed to identify the
corresponding genes. A chromosomal DNA segment of about 14 kbp was sequenced
which contained 10 genes transcribed in the same direction. These are organized
in two adjacent gene clusters and include the genes coding for five identified
phenol-induced proteins. Comparison with sequences in the databases revealed the
following similarities: the gene products of two open reading frames (ORFs) are
each similar to either the central part and N-terminal part of
phosphoenolpyruvate synthases. We propose that these ORFs are components of the
phenylphosphate synthase system. Three ORFs showed similarity to the ubiD gene
product, 3-octaprenyl-4-hydroxybenzoate carboxy lyase; UbiD catalyzes the
decarboxylation of a 4-hydroxybenzoate analogue in ubiquinone biosynthesis.
Another ORF was similar to the ubiX gene product, an isoenzyme of UbiD. We
propose that (some of) these four proteins are involved in the carboxylation of
phenylphosphate. A 700-bp PCR product derived from one of these ORFs cross
hybridized with DNA from different Thauera and Azoarcus strains, even from those
which have not been reported to grow with phenol. One ORF showed similarity to
the mutT gene product, and three ORFs showed no strong similarities to sequences
in the databases. Upstream of the first gene cluster, an ORF which is transcribed
in the opposite direction codes for a protein highly similar to the DmpR
regulatory protein of Pseudomonas putida. DmpR controls transcription of the
genes of aerobic phenol metabolism, suggesting a similar regulation of anaerobic
phenol metabolism by the putative regulator.
PMID- 11004187
TI - Identification of a copper-responsive two-component system on the chromosome of
Escherichia coli K-12.
AB - Using a genetic screen we have identified two chromosomal genes, cusRS (ylcA
ybcZ), from Escherichia coli K-12 that encode a two-component, signal
transduction system that is responsive to copper ions. This regulatory system is
required for copper-induced expression of pcoE, a plasmid-borne gene from the E.
coli copper resistance operon pco. The closest homologs of CusR and CusS are
plasmid-borne two-component systems that are also involved in metal responsive
gene regulation: PcoR and PcoS from the pco operon of E. coli; CopR and CopS from
the cop operon, which provides copper resistance to Pseudomonas syringae; and
SilR and SilS from the sil locus, which provides silver ion resistance to
Salmonella enterica serovar Typhimurium. The genes cusRS are also required for
the copper-dependent expression of at least one chromosomal gene, designated cusC
(ylcB), which is allelic to the recently identified virulence gene ibeB in E.
coli K1. The cus locus may comprise a copper ion efflux system, because the
expression of cusC is induced by high concentrations of copper ions. Furthermore,
the translation products of cusC and additional downstream genes are homologous
to known metal ion antiporters.
PMID- 11004188
TI - The last RNA-binding repeat of the Escherichia coli ribosomal protein S1 is
specifically involved in autogenous control.
AB - The ssyF29 mutation, originally selected as an extragenic suppressor of a protein
export defect, has been mapped within the rpsA gene encoding ribosomal protein
S1. Here, we examine the nature of this mutation and its effect on translation.
Sequencing of the rpsA gene from the ssyF mutant has revealed that, due to an
IS10R insertion, its product lacks the last 92 residues of the wild-type S1
protein corresponding to one of the four homologous repeats of the RNA-binding
domain. To investigate how this truncation affects translation, we have created
two series of Escherichia coli strains (rpsA(+) and ssyF) bearing various
translation initiation regions (TIRs) fused to the chromosomal lacZ gene. Using a
beta-galactosidase assay, we show that none of these TIRs differ in activity
between ssyF and rpsA(+) cells, except for the rpsA TIR: the latter is stimulated
threefold in ssyF cells, provided it retains at least ca. 90 nucleotides upstream
of the start codon. Similarly, the activity of this TIR can be severely repressed
in trans by excess S1, again provided it retains the same minimal upstream
sequence. Thus, the ssyF stimulation requires the presence of the rpsA
translational autogenous operator. As an interpretation, we propose that the ssyF
mutation relieves the residual repression caused by normal supply of S1 (i.e.,
that it impairs autogenous control). Thus, the C-terminal repeat of the S1 RNA
binding domain appears to be required for autoregulation, but not for overall
mRNA recognition.
PMID- 11004189
TI - Characterization of tpp1(+) as encoding a main trehalose-6P phosphatase in the
fission yeast Schizosaccharomyces pombe.
AB - We have characterized an open reading frame of 2,454 bp on chromosome I of
Schizosaccharomyces pombe as the gene encoding trehalose-6P phosphatase
(tpp1(+)). Disruption of tpp1(+) caused in vivo accumulation of trehalose-6P upon
heat shock and prevented cell growth at 37 to 40 degrees C. Accumulation of
trehalose-6P in cells bearing a chromosomal disruption of the tpp1(+) gene and
containing a plasmid with tpp1(+) under the control of the thiamine-repressible
promotor correlated with tpp1(+) repression. The level of tpp1(+) mRNA rose upon
heat shock, osmostress, or oxidative stress and was negatively controlled by
cyclic AMP-dependent protein kinase activity. Expression of tpp1(+) during
oxidative or osmotic stress, but not during heat shock, was under positive
control by the wis1-sty1 (equivalent to phh1 and spc1) mitogen-activated protein
kinase pathway. Analysis of Tpp1 protein levels suggests that the synthesis of
trehalose-6P phosphatase may also be subjected to translational or
posttranslational control.
PMID- 11004190
TI - Transcriptional control of the sulfur-regulated cysH operon, containing genes
involved in L-cysteine biosynthesis in Bacillus subtilis.
AB - The molecular mechanisms of regulation of the genes involved in the biosynthesis
of cysteine are poorly characterized in Bacillus subtilis and other gram-positive
bacteria. In this study we describe the expression pattern of the B. subtilis
cysH operon in response to sulfur starvation. A 6.1-kb polycistronic transcript
which includes the cysH, cysP, ylnB, ylnC, ylnD, ylnE, and ylnF genes was
identified. Its synthesis was induced by sulfur limitation and strongly repressed
by cysteine. The cysH operon contains a 5' leader portion homologous to that of
the S box family of genes involved in sulfur metabolism, which are regulated by a
transcription termination control system. Here we show that induction of B.
subtilis cysH operon expression is dependent on the promoter and independent of
the leader region terminator, indicating that the operon is regulated at the
level of transcription initiation rather than controlled at the level of
premature termination of transcription. Deletion of a 46-bp region adjacent to
the -35 region of the cysH promoter led to high-level expression of the operon,
even in the presence of cysteine. We also found that O-acetyl-L-serine (OAS), a
direct precursor of cysteine, renders cysH transcription independent of sulfur
starvation and insensitive to cysteine repression. We propose that transcription
of the cysH operon is negatively regulated by a transcriptional repressor whose
activity is controlled by the intracellular levels of OAS. Cysteine is predicted
to repress transcription by inhibiting the synthesis of OAS, which would act as
an inducer of cysH expression. These novel results provide the first direct
evidence that cysteine biosynthesis is controlled at a transcriptional level by
both negative and positive effectors in a gram-positive organism.
PMID- 11004191
TI - SarA represses agr operon expression in a purified in vitro Staphylococcus aureus
transcription system.
AB - Mutation and genetic complementation studies suggested that two chromosomal loci,
agr and sar, are involved in the upregulation of several exotoxin genes and the
downregulation of a number of surface protein genes in a growth phase-dependent
manner in Staphylococcus aureus. We purified recombinant T7-tagged SarA from
Escherichia coli and determined its effect on transcription from several S.
aureus promoters by using purified RNA polymerase reconstituted with either
sigma(A) or sigma(B) from S. aureus. Of the seven sigma(A)-dependent promoters
that we tested, SarA repressed transcription from agrP2, agrP3, cna, sarP1, and
sea promoters and did not affect sec and znt promoters. Furthermore, SarA had no
effect on transcription from the sigma(B)-dependent sarP3 promoter. In vitro
experimental data presented in this report suggest that SarA expression is
autoregulated.
PMID- 11004192
TI - Null mutation of the dam or seqA gene suppresses temperature-sensitive lethality
but not hypersensitivity to novobiocin of muk null mutants.
AB - Escherichia coli mukF, mukE, and mukB null mutants have common phenotypes such as
temperature-dependent colony formation, anucleate cell production, chromosome
cutting by septum closure, and abnormal localization of SeqA-DNA clusters. We
show here that the associated muk null mutations cause hypersensitivity to
novobiocin. Null mutation of either dam or seqA suppressed partially the
temperature-sensitive lethality but failed to suppress the anucleate cell
production and the hypersensitivity to novobiocin caused by muk null mutations.
PMID- 11004193
TI - New virulence-activated and virulence-repressed genes identified by systematic
gene inactivation and generation of transcriptional fusions in Bordetella
pertussis.
AB - An in silico scan of the partially completed genome sequence of Bordetella
pertussis and analyses of transcriptional fusions generated with a new
integrational vector were used to identify new potential virulence genes. The
genes encoding a putative siderophore receptor, adhesins, and an autotransporter
protein appeared to be regulated in a manner similar to Bordetella virulence
genes by the global virulence regulator BvgAS. In contrast, the gene encoding a
putative intimin-like protein appeared to be repressed under conditions of
virulence.
PMID- 11004194
TI - A large gene cluster for the Clostridium cellulovorans cellulosome.
AB - A large gene cluster for the Clostridium cellulovorans cellulosome has been
cloned and sequenced upstream and downstream of the cbpA and exgS genes (C.-C.
Liu and R. H. Doi, Gene 211:39-47, 1998). Gene walking revealed that the engL
gene cluster (Y. Tamaru and R. H. Doi, J. Bacteriol. 182:244-247, 2000) was
located downstream of the cbpA-exgS genes. Further DNA sequencing revealed that
this cluster contains the genes for the scaffolding protein CbpA, the
exoglucanase ExgS, several endoglucanases of family 9, the mannanase ManA, and
the hydrophobic protein HbpA containing a surface layer homology domain and a
hydrophobic (or cohesin) domain. The sequence of the clustered genes is cbpA-exgS
engH-engK-hbpA-engL-man A-engM-engN and is about 22 kb in length. The engN gene
did not have a complete catalytic domain, indicating that engN is a truncated
gene. This large gene cluster is flanked at the 5' end by a putative
noncellulosomal operon consisting of nifV-orf1-sigX-regA and at the 3' end by
noncellulosomal genes with homology to transposase (trp) and malate permease
(mle). Since gene clusters for the cellulosome are also found in C.
cellulolyticum and C. josui, they seem to be typical of mesophilic clostridia,
indicating that the large gene clusters may arise from a common ancestor with
some evolutionary modifications.
PMID- 11004195
TI - Organization and expression of a Thermus thermophilus arginine cluster: presence
of unidentified open reading frames and absence of a Shine-Dalgarno sequence.
AB - A group of genes regulated by arginine was found clustered in the order argF-ORF1
argC-argJ-ORF4 between other, as yet uncharacterized, open reading frames (ORFs).
Transcription starts were identified immediately upstream from argF and ORF4.
Arginine repressed transcription that was initiated at argF but induced
transcription of ORF4. The functions of ORF1 and ORF4 are unknown, but analysis
of the sequence of ORF4 suggests that it is a membrane protein, possibly involved
in transport of arginine or a related metabolite. Mobility shift and DNase I
footprinting have revealed specific binding of pure Escherichia coli ArgR to the
promoter region of Thermus thermophilus argF. These results suggest that argF
transcription is controlled by a repressor homologous to those characterized in
enteric bacteria and bacilli. Thermus argF mRNA is devoid of Shine-Dalgarno (SD)
sequences. However, downstream from the ATG start codon of argF and many other
Thermus genes (with or without an SD box), sequences were found to be
complementary to nucleotides 1392 to 1409 of Thermus 16S rRNA, suggesting that an
mRNA-rRNA base pairing in this region is important for correct translation
initiation.
PMID- 11004196
TI - Mobilization of poly(3-hydroxybutyrate) in Ralstonia eutropha.
AB - Ralstonia eutropha H16 degraded (mobilized) previously accumulated poly(3
hydroxybutyrate) (PHB) in the absence of an exogenous carbon source and used the
degradation products for growth and survival. Isolated native PHB granules of
mobilized R. eutropha cells released 3-hydroxybutyrate (3HB) at a threefold
higher rate than did control granules of nonmobilized bacteria. No 3HB was
released by native PHB granules of recombinant Escherichia coli expressing the
PHB biosynthetic genes. Native PHB granules isolated from chromosomal knockout
mutants of an intracellular PHB (i-PHB) depolymerase gene of R. eutropha H16 and
HF210 showed a reduced but not completely eliminated activity of 3HB release and
indicated the presence of i-PHB depolymerase isoenzymes.
PMID- 11004197
TI - The Streptococcus pneumoniae beta-galactosidase is a surface protein.
AB - The beta-galactosidase gene of Streptococcus pneumoniae, bgaA, encodes a putative
2,235-amino-acid protein with the two amino acid motifs characteristic of the
glycosyl hydrolase family of proteins. In addition, an N-terminal signal sequence
and a C-terminal LPXTG motif typical of surface-associated proteins of gram
positive bacteria are present. Trypsin treatment of cells resulted in
solubilization of the enzyme, documenting that it is associated with the cell
envelope. In order to obtain defined mutants suitable for lacZ reporter
experiments, the bgaA gene was disrupted, resulting in a complete absence of
endogenous beta-galactosidase activity. The results are consistent with beta
galactosidase being a surface protein that seems not to be involved in lactose
metabolism but that may play a role during pathogenesis.
PMID- 11004198
TI - No genetic barriers between Salmonella enterica serovar typhimurium and
Escherichia coli in SOS-induced mismatch repair-deficient cells.
AB - Conjugational crosses trigger SOS induction in Escherichia coli F(-) cells mated
with Salmonella enterica serovar Typhimurium Hfr donors. Using an epigenetic
indicator of SOS induction, we showed that a strong SOS response occurring in a
subpopulation of mated mismatch repair-deficient cells totally abolishes genetic
barriers between these two genera.
PMID- 11004199
TI - On the architecture of the gram-negative bacterial murein sacculus.
AB - The peptidoglycan network of the murein sacculus must be porous so that
nutrients, waste products, and secreted proteins can pass through. Using
Escherichia coli and Pseudomonas aeruginosa as a baseline for gram-negative
sacculi, the hole size distribution in the peptidoglycan network has been modeled
by computer simulation to deduce the network's properties. By requiring that the
distribution of glycan chain lengths predicted by the model be in accord with the
distribution observed, we conclude that the holes are slits running essentially
perpendicular to the local axis of the glycan chains (i. e., the slits run along
the long axis of the cell). This result is in accord with previous permeability
measurements of Beveridge and Jack and Demchik and Koch. We outline possible
advantages that might accrue to the bacterium via this architecture and suggest
ways in which such defect structures might be detected. Certainly, large
molecules do penetrate the peptidoglycan layer of gram-negative bacteria, and the
small slits that we suggest might be made larger by the bacterium.
PMID- 11004200
TI - Identification in Listeria monocytogenes of MecA, a homologue of the Bacillus
subtilis competence regulatory protein.
AB - We identified in Listeria monocytogenes a gene encoding a protein homologous to
MecA, a regulatory protein acting with ClpC and ComK in the competence pathway of
Bacillus subtilis. In L. monocytogenes, MecA is involved, along with ClpC and
ClpP, in the downregulation of a 64-kDa secreted protein. In B. subtilis, the
MecA protein of L. monocytogenes behaves as a regulatory protein, controlling the
transcription of comK and comG. Complete or disrupted ComK homologues were also
found in L. monocytogenes. However, we failed to detect competence in various
strains of L. monocytogenes, including those with intact ComK. Our results
suggest that the functions of MecA in the saprophytes L. monocytogenes and B.
subtilis have presumably diverged in response to their respective ecological
niches.
PMID- 11004201
TI - Regulation of exocytosis by protein kinases and Ca(2+) in pancreatic duct
epithelial cells.
AB - We asked if the mechanisms of exocytosis and its regulation in epithelial cells
share features with those in excitable cells. Cultured dog pancreatic duct
epithelial cells were loaded with an oxidizable neurotransmitter, dopamine or
serotonin, and the subsequent release of these exogenous molecules during
exocytosis was detected by carbon-fiber amperometry. Loaded cells displayed
spontaneous exocytosis that may represent constitutive membrane transport. The
quantal amperometric events induced by fusion of single vesicles had a rapid
onset and decay, resembling those in adrenal chromaffin cells and serotonin
secreting leech neurons. Quantal events were frequently preceded by a "foot,"
assumed to be leak of transmitters through a transient fusion pore, suggesting
that those cell types share a common fusion mechanism. As in neurons and
endocrine cells, exocytosis in the epithelial cells could be evoked by elevating
cytoplasmic Ca(2+) using ionomycin. Unlike in neurons, hyperosmotic solutions
decreased exocytosis in the epithelial cells, and giant amperometric events
composed of many concurrent quantal events were observed occasionally. Agents
known to increase intracellular cAMP in the cells, such as forskolin,
epinephrine, vasoactive intestinal peptide, or 8-Br-cAMP, increased the rate of
exocytosis. The forskolin effect was inhibited by the Rp-isomer of cAMPS, a
specific antagonist of protein kinase A, whereas the Sp-isomer, a specific
agonist of PKA, evoked exocytosis. Thus, PKA is a downstream effector of cAMP.
Finally, activation of protein kinase C by phorbol-12-myristate-13-acetate also
increased exocytosis. The PMA effect was not mimicked by the inactive analogue,
4alpha-phorbol-12,13-didecanoate, and it was blocked by the PKC antagonist,
bisindolylmaleimide I. Elevation of intracellular Ca(2+) was not needed for the
actions of forskolin or PMA. In summary, exocytosis in epithelial cells can be
stimulated directly by Ca(2+), PKA, or PKC, and is mediated by physical
mechanisms similar to those in neurons and endocrine cells.
PMID- 11004202
TI - Time course and Ca(2+) dependence of sensitivity modulation in cyclic GMP-gated
currents of intact cone photoreceptors.
AB - We determined the Ca(2+) dependence and time course of the modulation of ligand
sensitivity in cGMP-gated currents of intact cone photoreceptors. In electro
permeabilized single cones isolated from striped bass, we measured outer segment
current amplitude as a function of cGMP or 8Br-cGMP concentrations in the
presence of various Ca(2+) levels. The dependence of current amplitude on
nucleotide concentration is well described by the Hill function with values of
K(1/2), the ligand concentration that half-saturates current, that, in turn,
depend on Ca(2+). K(1/2) increases as Ca(2+) rises, and this dependence is well
described by a modified Michaelis-Menten function, indicating that modulation
arises from the interaction of Ca(2+) with a single site without apparent
cooperativity. (Ca)K(m), the Michaelis-Menten constant for Ca(2+) concentration
is 857 +/- 68 nM for cGMP and 863 +/- 51 for 8Br-cGMP. In single cones under
whole-cell voltage clamp, we simultaneously measured changes in membrane current
and outer segment free Ca(2+) caused by sudden Ca(2+) sequestration attained by
uncaging diazo-2. In the presence of constant 8Br-cGMP, 15 micro, Ca(2+)
concentration decrease was complete within 50 ms and membrane conductance was
enhanced 2.33 +/- 0.95-fold with a mean time to peak of 1.25 +/- 0.23 s. We
developed a model that assumes channel modulation is a pseudo-first-order process
kinetically limited by free Ca(2+). Based on the experimentally measured changes
in Ca(2+) concentration, model simulations match experimental data well by
assigning the pseudo-first-order time constant a mean value of 0.40 +/- 0.14 s.
Thus, Ca(2+)-dependent ligand modulation occurs over the concentration range of
the normal, dark-adapted cone. Its time course suggests that its functional
effects are important in the recovery of the cone photoresponse to a flash of
light and during the response to steps of light, when cones adapt.
PMID- 11004203
TI - Cysteine modification of a putative pore residue in ClC-0: implication for the
pore stoichiometry of ClC chloride channels.
AB - The ClC channel family consists of chloride channels important for various
physiological functions. Two members in this family, ClC-0 and ClC-1, share
approximately 50-60% amino acid identity and show similar gating behaviors.
Although they both contain two subunits, the number of pores present in the
homodimeric channel is controversial. The double-barrel model proposed for ClC-0
was recently challenged by a one-pore model partly based on experiments with ClC
1 exploiting cysteine mutagenesis followed by modification with
methanethiosulfonate (MTS) reagents. To investigate the pore stoichiometry of ClC
0 more rigorously, we applied a similar strategy of MTS modification in an
inactivation-suppressed mutant (C212S) of ClC-0. Mutation of lysine 165 to
cysteine (K165C) rendered the channel nonfunctional, but modification of the
introduced cysteine by 2-aminoethyl MTS (MTSEA) recovered functional channels
with altered properties of gating-permeation coupling. The fast gate of the MTSEA
modified K165C homodimer responded to external Cl(-) less effectively, so the
P(o)-V curve was shifted to a more depolarized potential by approximately 45 mV.
The K165C-K165 heterodimer showed double-barrel-like channel activity after MTSEA
modification, with the fast-gating behaviors mimicking a combination of those of
the mutant and the wild-type pore, as expected for the two-pore model. Without
MTSEA modification, the heterodimer showed only one pore, and was easier to
inactivate than the two-pore channel. These results showed that K165 is important
for both the fast and slow gating of ClC-0. Therefore, the effects of MTS
reagents on channel gating need to be carefully considered when interpreting the
apparent modification rate.
PMID- 11004204
TI - Calcium wave propagation in pancreatic acinar cells: functional interaction of
inositol 1,4,5-trisphosphate receptors, ryanodine receptors, and mitochondria.
AB - In pancreatic acinar cells, inositol 1,4,5-trisphosphate (InsP(3))-dependent
cytosolic calcium ([Ca(2+)](i)) increases resulting from agonist stimulation are
initiated in an apical "trigger zone," where the vast majority of InsP(3)
receptors (InsP(3)R) are localized. At threshold stimulation, [Ca(2+)](i) signals
are confined to this region, whereas at concentrations of agonists that optimally
evoke secretion, a global Ca(2+) wave results. Simple diffusion of Ca(2+) from
the trigger zone is unlikely to account for a global [Ca(2+)](i) elevation.
Furthermore, mitochondrial import has been reported to limit Ca(2+) diffusion
from the trigger zone. As such, there is no consensus as to how local [Ca(2+)](i)
signals become global responses. This study therefore investigated the mechanism
responsible for these events. Agonist-evoked [Ca(2+)](i) oscillations were
converted to sustained [Ca(2+)](i) increases after inhibition of mitochondrial
Ca(2+) import. These [Ca(2+)](i) increases were dependent on Ca(2+) release from
the endoplasmic reticulum and were blocked by 100 microM ryanodine. Similarly,
"uncaging" of physiological [Ca(2+)](i) levels in whole-cell patch-clamped cells
resulted in rapid activation of a Ca(2+)-activated current, the recovery of which
was prolonged by inhibition of mitochondrial import. This effect was also
abolished by ryanodine receptor (RyR) blockade. Photolysis of d-myo InsP(3)
P(4(5))-1-(2-nitrophenyl)-ethyl ester (caged InsP(3)) produced either apically
localized or global [Ca(2+)](i) increases in a dose-dependent manner, as
visualized by digital imaging. Mitochondrial inhibition permitted apically
localized increases to propagate throughout the cell as a wave, but this
propagation was inhibited by ryanodine and was not seen for minimal control
responses resembling [Ca(2+)](i) puffs. Global [Ca(2+)](i) rises initiated by
InsP(3) were also reduced by ryanodine, limiting the increase to a region
slightly larger than the trigger zone. These data suggest that, while Ca(2+)
release is initially triggered through InsP(3)R, release by RyRs is the dominant
mechanism for propagating global waves. In addition, mitochondrial Ca(2+) import
controls the spread of Ca(2+) throughout acinar cells by modulating RyR
activation.
PMID- 11004205
TI - Pore block versus intrinsic gating in the mechanism of inward rectification in
strongly rectifying IRK1 channels.
AB - The IRK1 channel is inhibited by intracellular cations such as Mg(2+) and
polyamines in a voltage-dependent manner, which renders its I-V curve strongly
inwardly rectifying. However, even in excised patches exhaustively perfused with
a commonly used artificial intracellular solution nominally free of Mg(2+) and
polyamines, the macroscopic I-V curve of the channels displays modest
rectification. This observation forms the basis of a hypothesis, alternative to
the pore-blocking hypothesis, that inward rectification reflects the enhancement
of intrinsic channel gating by intracellular cations. We find, however, that
residual rectification is caused primarily by the commonly used pH buffer HEPES
and/or some accompanying impurity. Therefore, inward rectification in the strong
rectifier IRK1, as in the weak rectifier ROMK1, can be accounted for by voltage
dependent block of its ion conduction pore by intracellular cations.
PMID- 11004207
TI - Protein translocation across planar bilayers by the colicin Ia channel-forming
domain: where will it end?
AB - Colicin Ia, a 626-residue bactericidal protein, consists of three domains, with
the carboxy-terminal domain (C domain) responsible for channel formation. Whole
colicin Ia or C domain added to a planar lipid bilayer membrane forms voltage
gated channels. We have shown previously that the channel formed by whole colicin
Ia has four membrane-spanning segments and an approximately 68-residue segment
translocated across the membrane. Various experimental interventions could cause
a longer or shorter segment within the C domain to be translocated, making us
wonder why translocation normally stops where it does, near the amino-terminal
end of the C domain (approximately residue 450). We hypothesized that regions
upstream from the C domain prevent its amino-terminal end from moving into and
across the membrane. To test this idea, we prepared C domain with a ligand
attached near its amino terminus, added it to one side of a planar bilayer to
form channels, and then probed from the opposite side with a water-soluble
protein that can specifically bind the ligand. The binding of the probe had a
dramatic effect on channel gating, demonstrating that the ligand (and hence the
amino-terminal end of the C domain) had moved across the membrane. Experiments
with larger colicin Ia fragments showed that a region of more than 165 residues,
upstream from the C domain, can also move across the membrane. All of the colicin
Ia carboxy-terminal fragments that we examined form channels that pass from a
state of relatively normal conductance to a low-conductance state; we interpret
this passage as a transition from a channel with four membrane-spanning segments
to one with only three.
PMID- 11004206
TI - Ion interactions in the high-affinity binding locus of a voltage-gated Ca(2+)
channel.
AB - The selectivity filter of voltage-gated Ca(2+) channels is in part composed of
four Glu residues, termed the EEEE locus. Ion selectivity in Ca(2+) channels is
based on interactions between permeant ions and the EEEE locus: in a mixture of
ions, all of which can pass through the pore when present alone, those ions that
bind weakly are impermeant, those that bind more strongly are permeant, and those
that bind more strongly yet act as pore blockers as a consequence of their low
rate of unbinding from the EEEE locus. Thus, competition among ion species is a
determining feature of selectivity filter function in Ca(2+) channels. Previous
work has shown that Asp and Ala substitutions in the EEEE locus reduce ion
selectivity by weakening ion binding affinity. Here we describe for wild-type and
EEEE locus mutants an analysis at the single channel level of competition between
Cd(2+), which binds very tightly within the EEEE locus, and Ba(2+) or Li(+),
which bind less tightly and hence exhibit high flux rates: Cd(2+) binds to the
EEEE locus approximately 10(4)x more tightly than does Ba(2+), and approximately
10(8)x more tightly than does Li(+). For wild-type channels, Cd(2+) entry into
the EEEE locus was 400x faster when Li(+) rather than Ba(2+) was the current
carrier, reflecting the large difference between Ba(2+) and Li(+) in affinity for
the EEEE locus. For the substitution mutants, analysis of Cd(2+) block kinetics
shows that their weakened ion binding affinity can result from either a reduction
in blocker on rate or an enhancement of blocker off rate. Which of these rate
effects underlay weakened binding was not specified by the nature of the mutation
(Asp vs. Ala), but was instead determined by the valence and affinity of the
current-carrying ion (Ba(2+) vs. Li(+)). The dependence of Cd(2+) block kinetics
upon properties of the current-carrying ion can be understood by considering the
number of EEEE locus oxygen atoms available to interact with the different ion
pairs.
PMID- 11004208
TI - Effect of luminal atrial natriuretic peptide on chloride reabsorption in mouse
cortical thick ascending limb: inhibition by endothelin.
AB - Insofar as neutral endopeptidase inhibition has afforded evidence for a tubular
luminal action of atrial natriuretic peptide (ANP), the present study was
undertaken to investigate a possible effect of the peptide on chloride
reabsorption (JCl) in thick ascending limb (TAL). Luminal addition of ANP to in
vitro microperfused cortical TAL (CTAL) significantly decreased JCl with a
threshold and a maximum concentration of 10(-12) M and 10(-9) M, respectively. A
similar effect of 10(-9) M ANP was observed in medullary TAL (MTAL). The effect
of luminal ANP was significantly reduced by HS-142-1, a specific inhibitor of
guanylyl cyclase receptor, and by H-8, a protein kinase G inhibitor, but was not
affected by the protein kinase C inhibitor bisindolylmaleimide I. Unexpectedly,
the effect of ANP was not additive with that of endothelin (ET), a peptide that
was previously shown to decrease JCl in TAL through a calcium-independent,
protein kinase C-mediated pathway. Indeed, ET-1 (10(-8) M in the lumen)
significantly decreased JCl and prevented a further effect of ANP on the same
tubule. Similarly, the decrease of JCl induced by simultaneous addition of ET and
ANP was not higher than that obtained with each agent alone. Conversely, the
inhibitory effect of ANP was enhanced in the presence of cyclic guanosine
monophosphate (cGMP; 10(-6) M in the lumen). ET-1 significantly attenuated the
ANP-stimulated generation of cGMP in microdissected CTAL and failed to prevent a
further decrease of JCl promoted by a permeant cGMP analogue. It is concluded
that luminal ANP decreased Cl reabsorption in mouse CTAL and MTAL. This effect
was abrogated by ET-1 as a result of the inhibition of ANP-stimulated cGMP
generation.
PMID- 11004209
TI - The luminal P2Y receptor in the isolated perfused mouse cortical collecting duct.
AB - Extracellular nucleotides regulate renal ion transport. With the use of in vitro
perfusion and [Ca(2+)](i) imaging, this study investigated whether mouse and
rabbit cortical collecting ducts (CCD) respond to luminal nucleotides. In mouse
CCD, luminal ATP (EC(50): 10 microM) and UTP (EC(50): 9.7 microM) increased
[Ca(2+)](i) with an initial peak and a plateau. To make certain that basolateral
P2 receptors were not activated by luminal nucleotides via leak diffusion,
luminal trypsin (1 microM), a known agonist for basolateral proteinase-activated
receptors, was perfused. Mouse CCD that were responsive to luminal ATP were
nonresponsive to luminal trypsin but always showed [Ca(2+)](i) elevations by
basolateral trypsin (10 or 100 nM). Luminal alpha,beta- and beta,gamma-methylene
ATP, 2-methyl-S-ATP, ADP, UDP, and 2',3'-O-4-benzoylbenzoyl ATP had no effect
(100 microM, n = 9). Without external Ca(2+), luminal ATP still stimulated a
[Ca(2+)](i) increase. Mouse CCD also responded to basolateral ATP (EC(50): 23
microM) and UTP (EC(50): 23 microM) with smaller [Ca(2+)](i) elevations. Confocal
microscopy of perfused CCD showed that luminal ATP (100 microM) rapidly increased
[Ca(2+)](i) in nearly all cells (n = 6) and the same cells that responded to
luminal ATP responded to basolateral ATP (100 microM). In contrast, rabbit CCD
did not respond to luminal ATP/UTP (n = 8) despite ATP's known effect from the
basolateral side (EC(50): 34 microM). These data indicate the expression of
luminal P2Y receptors (probably P2Y(2)) in principal cells of mouse CCD but not
in rabbit CCD.
PMID- 11004210
TI - Inducible nitric oxide synthase attenuates endothelium-dependent renal
microvascular vasodilation.
AB - Previous studies have demonstrated that inducible nitric oxide synthase (iNOS)
plays a key pathophysiologic role during sepsis. The present study was designed
to delineate the consequences of iNOS activation on renal microvascular function.
Male Sprague-Dawley rats were given intraperitoneal injections of
lipopolysaccharide (LPS; 4 mg/kg) at 16 h and 4 h before experimentation.
Afferent and efferent arteriolar diameters from LPS-treated and control rats were
assessed in vitro with the use of the blood perfused juxtamedullary nephron
technique. Basal afferent and efferent arteriolar diameters of LPS-treated rats
averaged 19.7 +/- 0.9 (n = 7) and 18.3 +/- 1.0 microm (n = 5), respectively, and
were similar to those of control rats (20.8 +/- 0.3 [n = 6] and 18.4 +/- 0.6
microm [n = 6], respectively). Superfusion with the selective iNOS inhibitor S,S'
(1,3-phenylenebis[1,2-ethanediyl]) bisisothiourea (PBIT), at the doses of 0.01,
0.1, and 1 microM, significantly decreased afferent and efferent arteriolar
diameters in a dose-dependent manner, whereas afferent or efferent arteriolar
diameters of control rats were not altered in response to the same doses of PBIT.
In the second series of experiments, superfusion with 10 microM acetylcholine
(ACh) significantly increased afferent and efferent arteriolar diameters of LPS
treated rats by 14.9 +/- 1.6% (n = 9) and 6.6 +/- 1.1% (n = 6), respectively. The
ACh-induced afferent and efferent arteriolar dilator responses were inhibited by
superfusion with the nonselective NOS inhibitor N:(omega)-nitro-L-arginine (100
microM). However, afferent and efferent arteriolar dilator responses to ACh were
significantly enhanced during selective iNOS inhibition with 1 microM PBIT (40.1
+/- 0.7% and 25.2 +/- 1.3%, respectively). These results suggest that activation
of iNOS by LPS increases the influence of nitric oxide on afferent and efferent
arteriolar tone and impairs endothelium-dependent nitric oxide effects.
PMID- 11004211
TI - Renin inhibition improves pressure natriuresis in essential hypertension.
AB - Pressure natriuresis (PN), i.e., a rise in renal sodium excretion in response to
a higher BP, is involved in long-term BP regulation. PN is blunted in essential
hypertension, but the mechanism is unknown. This study assessed the role of the
renin-angiotensin-aldosterone system (RAAS) in PN in eight essential hypertensive
men from the individual correlations between spontaneous fluctuations in BP and
time corresponding changes in sodium excretion (collected at 2- and 4-h intervals
for 48 h), during strict sodium balance, without treatment, and during renin
inhibition (remikiren, 600 mg oral compound). Without treatment, daily values for
mean arterial pressure were 109.5 +/- 1.9 and 107 +/- 1.9 mmHg, for urinary
sodium excretion were 37.2 +/- 2.8 and 42.0 +/- 2.8 mmol/24 h, and for plasma
renin activity were 2.34 +/- 0.48 and 2.23 +/- 0.44 nmol/L per h, respectively,
for two consecutive days. During remikiren treatment, mean arterial pressure was
101.9 +/- 1.7 and 100.8 +/- 1. 7 mmHg (P: < 0.05, versus baseline). Urinary
sodium excretion was 39. 3 +/- 3.7 and 45.2 +/- 5.3 mmol/24 h (not significant
versus baseline), and plasma renin activity was 0.79 +/- 0.11 and 0.82 +/- 0.13
nmol/L per h (P: < 0.05 versus baseline). During remikiren treatment, BP
correlated positively with sodium excretion in all patients but in only three of
eight patients without treatment. The slope of the regression equation was
steeper during remikiren treatment in seven of eight patients. Thus, the
relationship between BP and natriuresis was more readily apparent during RAAS
blockade, suggesting that RAAS activity blunts PN in hypertensive patients.
Improved PN may contribute to the hypotensive effect of RAAS blockade and to
maintenance of sodium balance at a lower BP level without volume expansion.
PMID- 11004212
TI - Stimulation of NADPH oxidase by oxidized low-density lipoprotein induces
proliferation of human vascular endothelial cells.
AB - Oxidized low-density lipoprotein (OxLDL) exerts proliferation and apoptosis in
vascular cells, depending on its concentration and the duration of exposure.
Recent studies indicate that [O(2)](-) is involved in cell cycle regulation and
that OxLDL stimulates endothelial cells to produce [O(2)](-). This study examined
the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as a
potential source for [O(2)](-) in the proliferation-inducing activity of OxLDL in
cultured human umbilical vein endothelial cells (HUVEC). Human LDL was oxidized
by Cu(++), and proliferation of HUVEC was detected by 3H-thymidine incorporation.
OxLDL (5 microg/ml) caused an increase in proliferation of HUVEC of 250 to 300%.
OxLDL-induced proliferation was blocked by addition of the antioxidants
superoxide dismutase and catalase, suggesting that enhanced [O(2)](-) formation
was involved. Diphenylene iodonium (DPI, 1 microM), an inhibitor of NADPH
oxidase, also prevented OxLDL-induced proliferation of HUVEC, indicating that
NADPH oxidase was the source for enhanced [O(2)](-) formation. The OxLDL effect
was mimicked by lysophosphatidylcholine (LPC, 10 microM), a compound formed
during oxidation of LDL. LPC-induced proliferation was also prevented by
coincubation with DPI. Treatment of HUVEC with [O(2)](-) generated by the
xanthine/xanthine oxidase reaction resulted in proliferation as did treatment
with OxLDL. As expected, this stimulation could not be blocked by DPI. With the
use of the cytochrome c-assay, it was demonstrated that OxLDL and LPC enhanced
[O(2)](-) formation in HUVEC (by factor 3.2 and by factor 3.5, respectively).
Supporting the assumption that NADPH oxidase was the enzyme responsible for
[O(2)](-) formation, cells transfected with antisense oligonucleotides for NADPH
oxidase showed a significantly reduced [O(2)](-) formation after stimulation with
OxLDL and LPC. OxLDL and its compound LPC induce proliferation of HUVEC through
activation of NADPH oxidase. The active NADPH oxidase generates [O(2)](-), which
mediates the proliferative effects.
PMID- 11004213
TI - Expression of LOX-1, an oxidized low-density lipoprotein receptor, in
experimental hypertensive glomerulosclerosis.
AB - Oxidized low-density lipoprotein (OxLDL) has been implicated in atherosclerosis
and glomerulosclerosis. LOX-1 is a recently identified OxLDL receptor that is
abundantly expressed in vascular endothelial cells. The aim of the present study
was to investigate LOX-1 expression in the kidneys of hypertensive rats. Dahl
salt-sensitive (DS) and salt-resistant (DR) rats were fed a 0.3% or 8% NaCl diet.
Some DS 8% rats were treated with manidipine or hydralazine. LOX-1 gene
expression was markedly elevated in the kidneys and glomeruli of hypertensive DS
8% rats compared with those of normotensive DR and DS 0.3% rats. Prolonged salt
loading further increased the renal LOX-1 expression in DS rats. The LOX-1
upregulation in DS 8% rats was accompanied by renal overexpression of
transforming growth factor-beta 1 and type I collagen, impaired renal function,
and histologic glomerulosclerotic changes, all of which were ameliorated by
antihypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo
and in cultured glomerular cells in vitro. However, LOX-1 expression was elevated
in the aorta but not the kidneys of spontaneously hypertensive rats, which
exhibited hypertension but minor glomerulosclerotic changes. In conclusion, the
LOX-1 upregulation in the kidney of DS 8% rats was parallel to glomerulosclerotic
changes and renal dysfunction, suggesting a possible pathogenetic role for renal
LOX-1 in the progression to hypertensive glomerulosclerosis.
PMID- 11004214
TI - Development of autosomal recessive polycystic kidney disease in BALB/c-cpk/cpk
mice.
AB - Autosomal recessive polycystic kidney disease (ARPKD) is a rare but devastating
inherited disease in humans. Various strains of mice that are homozygous for the
cpk gene display renal pathology similar to that seen in human ARPKD. The PKD
progresses to renal insufficiency, azotemia, and ultimately a uremic death by
approximately 3 wk of age. This study characterizes PKD in mice that are
homozygous for the cpk gene on a BALB/c inbred mouse background. The BALB/c
cpk/cpk murine model displays renal as well as extrarenal pathology similar to
that found in human ARPKD. The renal pathology includes the well-characterized
early proximal tubule and, later, massive collecting duct cysts. The extrarenal
defects in this murine model include common bile duct dilation, intrahepatic
biliary duct cysts with periductal hyperplasia, and pancreatic dysplasia with
cysts. Renal mRNA expression of c-myc, a proto-oncogene, and clusterin (SGP-2), a
marker associated with immature collecting ducts, decreases during normal
development but is upregulated in murine ARPKD. Expression of epidermal growth
factor (EGF) mRNA is significantly diminished, whereas EGF receptor mRNA is
upregulated in the BALB/c-cpk/cpk kidney compared with phenotypically normal
littermates. To determine whether the altered EGF expression contributes to the
development of PKD, neonatal mice were treated with exogenous EGF (1 microg/g
body wt injected subcutaneously on postnatal days 3 through 9). EGF treatment
reduced the relative kidney weight and common bile duct dilation and
downregulated renal expression of clusterin and EGF receptor. However, exogenous
EGF did not affect the degree of renal failure, the pancreatic pathology, or the
misregulated renal expression of c-myc. In summary, the present study
characterizes the renal and extrarenal pathology in the BALB/c-cpk/cpk murine
model of ARPKD. Renal mRNA expression of EGF is diminished in this mouse model.
EGF treatment did not prevent renal failure but ameliorated pathologic changes in
the kidney and the biliary ducts of the BALB/c-cpk/cpk mouse.
PMID- 11004215
TI - Expression of endothelial nitric oxide synthase in human peritoneal tissue:
regulation by Escherichia coli lipopolysaccharide.
AB - Changes in the expression of endothelial nitric oxide synthase (eNOS) in the
peritoneum could be involved in the peritoneal dysfunction associated with
peritoneal inflammation. Demonstrated recently in bovine endothelial cells was
the existence of cytosolic proteins that bind to the 3'-untranslated region (3'
UTR) of eNOS mRNA and could be implicated in eNOS mRNA stabilization. The present
work demonstrates that eNOS protein is expressed in human endothelial and
mesothelial peritoneal cells. Escherichia coli lipopolysaccharide shortened the
half-life of eNOS message, reducing eNOS protein expression in peritoneal
mesothelial and endothelial cells. Moreover, under basal conditions, human
peritoneal samples expressed cytosolic proteins that bind to the 3'-UTR of eNOS
mRNA. The cytosolic proteins that directly bind to 3'-UTR were identified as a 60
kD protein. After incubation of human peritoneal samples with lipopolysaccharide,
the binding activity of the cytosolic 60-kD protein increased in a time-dependent
manner. Studies are now necessary to determine the involvement of this 60-kD
protein in the regulation of eNOS expression in peritoneal cells and particularly
its involvement in the peritoneal dysfunction associated with inflammatory
reactions.
PMID- 11004216
TI - 1,25-Dihydroxy-19-nor-vitamin D(2), a vitamin D analog with reduced bone
resorbing activity in vitro.
AB - 1,25-Dihydroxy-19-nor-vitamin D(2) (19-norD(2)), a new analog of 1,25(OH)(2)D(3),
suppresses parathyroid hormone in renal failure patients and in uremic rats but
has less calcemic activity than 1,25(OH)(2)D(3). Although 19-norD(2) has high
affinity for the vitamin D receptor and similar pharmacokinetics to those of
1,25(OH)(2)D(3), it has much less bone resorbing activity in vivo. The intrinsic
activity of 19-norD(2) on osteoclastogenesis and activation of bone resorption in
mouse bone marrow cultures was examined to determine the mechanism involved. 19
norD(2) and 1,25(OH)(2)D(3) (10 nM) were equivalent in stimulating the formation
and maintenance of large multinucleated, tartrate-resistant acid phosphatase
positive cells. However, the amount of bone resorbed by osteoclasts stimulated by
10 nM 19-norD(2), as measured by pit-forming assays, was reduced 62% compared
with 10 nM 1,25(OH)(2)D(3)-stimulated osteoclasts (P < 0. 05). This difference
could not be attributed to enhanced catabolism or to downregulated vitamin D
receptor. The rate of degradation of 19-norD(2) in cultures was approximately 20%
greater than 1, 25(OH)(2)D(3), not enough to account for the different effects on
bone resorption. The VDR levels were identical in cultures that were treated with
19-norD(2) and 1,25(OH)(2)D(3). In summary, 19-norD(2) is less effective than
1,25(OH)(2)D(3) in stimulating mouse marrow osteoclasts to resorb bone. The
reason for this difference is not clear but seems to involve the late maturation
and/or activation of osteoclasts as the number of pits produced by each tartrate
resistant acid phosphatase-positive cell is reduced under stimulation by 19
norD(2) compared with 1,25(OH)(2)D(3).
PMID- 11004217
TI - The in vitro effect of calcitriol on parathyroid cell proliferation and
apoptosis.
AB - Calcitriol treatment is used to reduce parathyroid hormone levels in azotemic
patients with secondary hyperparathyroidism (HPT). Whether long-term calcitriol
administration reduces parathyroid gland size in patients with severe secondary
hyperparathyroidism is not clear. The aim of the study was to evaluate in vitro
the effect of calcitriol on parathyroid cell proliferation and apoptosis in
normal parathyroid glands and in adenomatous and hyperplastic human parathyroid
glands. Freshly harvested parathyroid glands from normal dogs and hyperplastic
and adenomatous glands from patients with secondary (2 degrees) and primary (1
degree) HPT undergoing parathyroidectomy were studied. Flow cytometry was used to
quantify the cell cycle and apoptosis of parathyroid cells. Apoptosis was also
evaluated by DNA electrophoresis and light and electron microscopy. In normal dog
parathyroid glands, culture with calcitriol (10(-10) to 10(-7) M) for 24 h
produced a dose-dependent inhibitory effect on the progression of cells into the
cell cycle and into apoptosis. When glands from patients with 2 degrees HPT were
cultured for 24 h, only high calcitriol concentrations (10(-7) M) inhibited the
progression through the cell cycle and the induction of apoptosis. In parathyroid
adenomas (1 degrees HPT), even a high concentration of calcitriol (10(-7) M) had
no significant effect on the cell cycle or apoptosis. The present study shows
that in vitro, calcitriol inhibits in a dose-dependent manner in normal
parathyroid glands both parathyroid cell proliferation and apoptosis. However, in
secondary hyperplasia, only high concentrations of calcitriol inhibited cell
proliferation and apoptosis. In 1 degree HPT, even high concentrations of
calcitriol had no effect. Because calcitriol simultaneously inhibits both cell
proliferation and apoptosis, a reduction in the parathyroid gland mass may not
occur as a direct effect of calcitriol treatment.
PMID- 11004218
TI - Urinary aquaporin 2 and calciuria correlate with the severity of enuresis in
children.
AB - This study examined the hypothesis that nocturnal enuresis might be paralleled by
aquaporin 2 (AQP2) urinary excretion. Eighty children who experienced nocturnal
enuresis were studied and compared with 9 healthy children. The 24-h urine
samples were divided into two portions: night collections and day collections.
Creatinine equivalents of urine samples from each patient were analyzed by
Western blotting. AQP2 levels were semiquantified by densitometric scanning and
reported as a ratio between the intensity of the signal in the day urine sample
versus the night urine sample (D/N AQP2 ratio). The D/N AQP2 ratio was 0.59 +/-
0.11 (n = 9) in healthy children and increased to 1.27 +/- 0.24 (n = 10) in a
subpopulation of enuretic children who had low nocturnal vasopressin levels. In
enuretic children who displayed hypercalciuria and had normal vasopressin levels,
the D/N AQP2 ratio was 1.05 +/- 0.27 (n = 8). These data indicate that reduced
secretion of vasopressin and absorptive hypercalciuria are independently
associated with an approximately twofold increase in the urinary D/N AQP2 ratio.
When low nocturnal vasopressin levels were associated with hypercalciuria, a
nearly threefold increase in the D/N AQP2 ratio was observed (1. 67 +/- 0.41, n =
11). In addition, in all enuretic patients tested, the urinary D/N AQP2 ratio
correlates perfectly with the severity of the disorder (nocturnal polyuria). The
findings reported in this article indicate that urinary AQP2 correlates with the
severity of enuresis in children.
PMID- 11004219
TI - Urinary albumin excretion is associated with renal functional abnormalities in a
nondiabetic population.
AB - Microalbuminuria (MA) is an important early sign of diabetic nephropathy.
Hyperfiltration and impaired filtration in relation to albuminuria has been well
investigated in diabetic subjects. This study tested the hypothesis that an
increased urinary albumin excretion (UAE) is associated with renal functional
abnormalities also in nondiabetic subjects. The relation between UAE and
creatinine clearances (Ccr) in 7728 nondiabetic subjects was studied. Subjects
were divided in four groups according to UAE (mg/24 h): 0 to 15 (control), 15 to
30 (high-normal albuminuria [HNA]), 30 to 300 (MA), >300 (macroalbuminuria). An
elevated filtration and a diminished filtration were defined as a Ccr exceeding
or below 2x the SD of the control group corrected for age and gender. Ccr
followed a parabolic trend, with a higher Ccr in the HNA as compared with control
and a lower Ccr in the MA and macroalbuminuria group as compared with HNA. With
each increasing UAE level, male sex, age, body mass index, minimal waist
circumference, systolic and diastolic BP, plasma glucose, and a positive family
history for diabetes all followed a significant linear increasing trend (P <
0.001). After adjustment for age, gender, body mass index, plasma glucose, a
positive family history for diabetes, systolic and diastolic BP, antihypertensive
medication, and smoking in a multivariate analysis, HNA and MA were independently
associated with an elevated filtration (RR 1.8 [95% confidence interval, 1.30 to
2.51] and 1.7 [1.17 to 2. 45]). Macroalbuminuria was independently associated
with a diminished filtration (4.3 [range, 1.97 to 9.36]). In conclusion, an
elevated UAE might be an important and early sign for progressive renal function
loss in a nondiabetic population.
PMID- 11004220
TI - Role of lipoprotein (a) and TGF-beta 1 in atherosclerosis of hemodialysis
patients.
AB - Atherosclerotic vascular disease is a major cause of death for uremic patients
who are on hemodialysis (HD). Recent evidence suggests that lipoprotein (a)
[Lp(a)] may aggravate atherosclerosis by inhibiting activation of transforming
growth factor-beta 1 (TGF-beta 1). Plasma Lp(a) and plasma TGF-beta 1 activation
in HD patients (n = 51), chronic renal failure patients not subjected to
hemodialysis (non-HD-CRF; n = 12), and healthy volunteers (control; n = 13) were
investigated. Plasma Lp(a) was significantly higher in HD (18.75 +/- 1.62 mg/ml)
and non-HD-CRF patients (25.0 +/- 8.4 mg/ml) than in control subjects (10.9 +/-
5.8 mg/ml). The degree of atherosclerosis in HD patients was assessed by
measuring the intima-media thickness (IMT) and plaque score with the use of an
ultrasound scanner. IMT and plaque score were higher in HD and non-HD-CRF
patients than in controls. A significant positive correlation was found in HD
patients between Lp(a) and IMT (r = 0. 377, P < 0.01) as well as between Lp(a)
and plaque score (r = 0.43, P < 0.01). Plasma total TGF-beta 1 significantly
increased in HD (119.8 +/- 53.5 ng/ml) and non-HD-CRF patients (93.2 +/- 25.0
ng/ml) compared with control subjects (17.7 +/- 6.4 ng/ml), whereas the plasma
level of mature (active) TGF-beta1 did not differ among the groups. When plasma
TGF-beta 1 and supernatant TGF-beta 1 from cultured peripheral mononuclear cells
were compared before and after an HD session, neither total nor mature TGF-beta 1
showed a significant difference between the values before and after an HD
session. There were no significant relationships between plasma total TGF-beta 1
and IMT or plaque score, between mature TGF-beta 1 and IMT or plaque score, or
between mature TGF-beta 1 and Lp(a). In conclusion, Lp(a) may be an important
atherogenic factor in CRF patients. However, it was not clarified whether Lp(a)
exerts its effect by inhibiting TGF-beta 1 activation in CRF patients.
PMID- 11004221
TI - Prognosis of anti-hepatitis C virus antibody-positive patients on regular
hemodialysis therapy.
AB - The prevalence of hepatitis C virus (HCV) infection is high in patients who are
on chronic hemodialysis, but the role of HCV infection and HCV-related liver
disease in the mortality of these patients has not been shown. Therefore, we
conducted a prospective cohort study of 1470 patients who were on chronic
hemodialysis (17 to 89 yr old) from 16 dialysis centers in Japan. Among them, 276
patients (18.8%) were positive for anti-HCV antibodies and 1194 patients were
negative. The patients were followed for 6 yr from 1993 to 1999. Only one case, a
patient from the anti-HCV-antibody-positive group, was lost to the follow-up
during this period. The mortality was higher in the anti-HCV-antibody-positive
group (91 of 276 patients died) than in the anti-HCV-antibody-negative group (277
of 1193 died) (33.0% versus 23.2%, P< 0.01). A Cox proportional hazard
examination showed that positivity for anti-HCV antibodies was one of the risk
factors for death with an adjusted relative risk of 1.57 (95% confidence
interval, 1.23 to 2.00). As a cause of death, hepatocellular carcinoma and liver
cirrhosis were significantly more frequent in the anti-HCV-antibody-positive
patients than in the anti-HCV-antibody-negative patients (5.5% versus 0.0%, P<
0.001; 8.8% versus 0.4%, P< 0.001, respectively). These findings show that the
mortality is increased in anti-HCV-antibody-positive patients who are on chronic
hemodialysis. Hepatocellular carcinoma and liver cirrhosis are factors that may
influence the mortality.
PMID- 11004222
TI - Avoidance of cyclosporine in renal transplantation: effects of daclizumab,
mycophenolate mofetil, and steroids.
AB - Cyclosporine (CsA) has been implicated in both acute and chronic graft
dysfunction. The addition of humanized IL-2 receptor antibody daclizumab (DZB) to
CsA-based immunosuppression decreases the rate of acute renal transplant
rejection. Therefore, 45 patients were evaluated in an immunosuppressive protocol
that included DZB, mycophenolate mofetil (MMF), and steroids without CsA. This
was a prospective, nonrandomized, open-label trial of the efficacy and safety of
the treatment. DZB was given intravenously at 2 mg/kg before transplantation and
then at 1 mg/kg every 2 wk for four doses, MMF was given orally at 3 g/d, and
methylprednisolone/prednisone was given at 7 mg/kg per day and tapered to 15 mg/d
at 6 mo. CsA was added to the regimen when patients developed acute rejection
episodes or adverse effects to steroids or MMF; 49% of patients were spared CsA
maintenance. Patients without CsA had lower serum creatinine at 6 mo and needed
fewer medications to control BP. Incidence of biopsyproven rejections was 31% and
occurred early (median, 10 d). These rejection episodes occurred earlier in
cadaver transplants (median, 7 d) and later in living donor transplants (median,
62 days). Acute rejections occurred at a higher frequency (46% versus 34%) and
earlier (6.5 versus 15 d) in patients with delayed graft function compared with
patients without delayed graft function. Most of the rejections were moderate and
easily reversible. The actuarial 1-yr graft survival was 95% with 100% patient
survival.
PMID- 11004223
TI - A meta-analysis of immunosuppression withdrawal trials in renal transplantation.
AB - Since the publication of previous meta-analyses of cyclosporine (CsA) and
prednisone withdrawal in renal transplant recipients, several additional
randomized controlled trials with longer follow-up have been reported. Currently,
in nine prednisone withdrawal trials (n = 1461), the proportion of patients with
acute rejection was increased by 0.14 (95% confidence interval = 0.10 to 0. 17, P
< 0.001). In nine prednisone withdrawal trials (n = 1899), the relative risk (RR;
RR = 1.0 indicates no risk) of graft failure after withdrawal was also increased
(RR = 1.40; range, 1.09 to 1.70, P = 0.012). There was no evidence of between
study heterogeneity for either acute rejection or graft failure in the prednisone
withdrawal trials by a chi(2) test (P > 0.05). In 10 CsA withdrawal trials (n =
1049), the proportion of patients with acute rejection was increased by 0.11
(0.07 to 0.15, P < 0.001). In 12 trials (n = 1151), the RR of graft failure after
CsA withdrawal was 1.06 (95% confidence interval, 0.82 to 1.29, P = 0.646), but a
chi(2) test indicated that there was study heterogeneity. However, there was no
evidence of heterogeneity in the six studies (n = 632) with at least 4.0 yr (5.8
+/- 1.7) of follow-up (RR = 0.92; range, 0.64 to 1.20, P = 0.569) or in the seven
trials (n = 962) published in peer-reviewed journals (RR = 0.95; range, 0.70 to
1.20 P = 0.682). Finally, in three trials (n = 259) that compared CsA and
prednisone withdrawal, there was a nonsignificant trend for less graft failure
with CsA withdrawal (RR = 0.63; range, 0.08 to 1.16, P = 0.190). Thus, unlike
prednisone withdrawal, CsA withdrawal in select patients seems to impart little
risk of long-term graft failure.
PMID- 11004224
TI - Effect of MTHFR 1298A-->C and MTHFR 677C-->T genotypes on total homocysteine,
folate, and vitamin B(12) plasma concentrations in kdiney graft recipients.
AB - The effect of 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A
->C on total homocysteine (tHcy), folate and vitamin B(12) levels was
investigated in 733 kidney graft recipients. The six major genotype combinations
were used as grouping variables, and age, gender, BMI, serum creatinine, and
creatinine clearance and ln-folate, ln-vitamin B(12), or logarithmus naturalis
tHcy (ln-tHcy) were used as covariates in three ANCOVA and multiple stepwise
linear regression models. Hyperhomocysteinemia was present in 49.7% of the
patients. The allele frequency of MTHFR 677T and 1298C was 0.319 and 0.326. MTHFR
genotype and all other variables were significant predictors of ln-tHcy (higher
tHcy plasma levels for MTHFR 677TT/1298AA versus all other five genotype groups:
P < 0. 05). BMI, creatinine clearance, ln-tHcy, and MTHFR genotype influenced ln
folate (lower folate levels for MTHFR 677TT/1298AA versus all other genotype
groups: P < 0.05). Creatinine clearance and ln-tHcy were the only predictors of
ln-vitamin B(12) levels. In a prespecified subgroup analysis (n = 496), the MTHFR
genotype also influenced tHcy levels and compound heterozygous patients had
significantly lower folate levels as compared with MTHFR 677CC/1298AA and
677CC/1298CC. This study shows that the MTHFR 677TT/1298AA and 677CT/1298AC
genotypes are significant predictors of tHcy and folate plasma levels.
PMID- 11004225
TI - Altered expression of type II sodium/phosphate cotransporter in polycystic kidney
disease.
AB - Renal phosphate (Pi) absorption is mediated via the type II sodium/Pi
cotransporter (NaPi-2) in the brush border membrane (BBM) of proximal tubules.
Simultaneous detection of NaPi-2 mRNA by in situ hybridization and of NaPi-2
immunoreactivity by immunohistochemistry was performed to investigate the
distribution of the cotransporter in healthy control rats and during progression
of autosomal dominant polycystic kidney disease (ADPKD). The purpose of the study
was to disclose a relation between proximal tubular cell differentiation and NaPi
2 expression. In controls, NaPi-2 expression was present in the entire proximal
tubule. In the Han:SPRD (cy/+) model for ADPKD, the proximal nephron is primarily
affected by the cystic changes. Epithelial proliferation and impaired epithelial
matrix interaction result in a loss of cell differentiation that eventually leads
to cystic enlargement of the nephron. Normal expression of NaPi-2 in this model
was found only in tubules with intact BBM. Loss of BBM and cellular
interdigitation were paralleled by the loss of NaPi-2 in situ hybridization and
immunoreactive signals. These changes were moderate and focal in 2-mo-old rats
and generalized all over the cortex after 8 mo. Advanced renal damage in the
older PKD group was associated with mild phosphaturia, which suggests functional
insufficiency of tubular NaPi-2 reabsorption. These data show how proliferative
changes and loss of tubular epithelial differentiation in ADPKD may prevent
functional expression of the NaPi-2 system in the proximal tubule in a rapidly
progressive manner. NaPi-2 in proximal tubule BBM is suggested to play an
important role in impaired tubular absorption of Pi in renal disease.
PMID- 11004226
TI - Cyclosporine avoidance.
PMID- 11004227
TI - Inherited disorders of renal magnesium handling.
AB - The genetic basis and cellular defects of a number of primary magnesium wasting
diseases have been elucidated over the past decade. This review correlates the
clinical pathophysiology with the primary defect and secondary changes in
cellular electrolyte transport. The described disorders include (1)
hypomagnesemia with secondary hypocalcemia, an earlyonset, autosomal-recessive
disease segregating with chromosome 9q12-22.2; (2) autosomal-dominant
hypomagnesemia caused by isolated renal magnesium wasting, mapped to chromosome
11q23; (3) hypomagnesemia with hypercalciuria and nephrocalcinosis, a recessive
condition caused by a mutation of the claudin 16 gene (3q27) coding for a tight
junctional protein that regulates paracellular Mg(2+) transport in the loop of
Henle; (4) autosomal-dominant hypoparathyroidism, a variably hypomagnesemic
disorder caused by inactivating mutations of the extracellular Ca(2+)/Mg(2+)
sensing receptor, CASR: gene, at 3q13.3-21 (a significant association between
common polymorphisms of the CASR: and extracellular Mg(2+) concentration has been
demonstrated in a healthy adult population); and (5) Gitelman syndrome, a
recessive form of hypomagnesemia caused by mutations in the distal tubular NaCl
cotransporter gene, SLC12A3, at 16q13. The basis for renal magnesium wasting in
this disease is not known. These inherited conditions affect different nephron
segments and different cell types and lead to variable but increasingly
distinguishable phenotypic presentations. No doubt, there are in the general
population other disorders that have not yet been identified or characterized.
The continued use of molecular techniques to probe the constitutive and
congenital disturbances of magnesium metabolism will increase the understanding
of cellular magnesium transport and provide new insights into the way these
diseases are diagnosed and managed.
PMID- 11004228
TI - Coronary heart disease in chronic renal insufficiency: some management
considerations.
PMID- 11004229
TI - New hope for the treatment of pulmonary hypertension: novel approaches to a
complex disease.
PMID- 11004230
TI - Fatty acid synthase inhibitors reduce food intake and body weight.
PMID- 11004231
TI - Changes in expression of platelet-derived growth factor and its receptors in the
lungs of newborn rats exposed to air or 60% O(2).
AB - PDGF-related gene expression has been well characterized during fetal rat lung
development and adult rat lung injury, but not during normal postnatal lung
growth or injury. Lung expression of the mRNA for PDGF-A, -B, -alpha R, and -beta
R and immunoreactive PDGF-AA, -BB, -alpha R, and -beta R were assessed in rat
pups raised in air or 60% O(2) for up to 14 d after birth. Expression of mRNA and
immunoreactive ligand did not correlate for pups raised in air. Immunoreactive
PDGF-alpha R and -beta R, but not PDGF-AA and -BB, were evident throughout the
lung at birth. Both PDGF-AA and -BB were evident in airway epithelium, PDGF-BB in
alveolar epithelial cells and PDGF-AA was widely distributed in parenchymal
tissue at 4 d. PDGF-alpha R was localized to airway epithelium, and PDGF-beta R
to subendothelial perivascular regions and to airway and alveolar epithelium at 4
d. Immunoreactive PDGF ligands all declined after 4 d. Intraperitoneal injection
of neutralizing antibodies or truncated soluble receptors to PDGF-BB reduced lung
DNA synthesis in air. Exposure to 60% O(2) significantly increased mRNA for PDGF
B, -beta R, and -alpha R, but not PDGF-A, relative to air-exposed lung at various
time points after birth. PDGF-A, -B, and -alpha R immunoreactivities in these
lungs were reduced and delayed, consistent with a global inhibition of lung
growth. Pups exposed to 60% O(2) had a similar distribution of PDGF-beta R to
that seen in air, except that at 14 d PDGF-beta R was distributed throughout the
lung parenchyma. We conclude that PDGF ligands and receptors are important for
normal postnatal lung growth and that their expression is delayed by O(2)
exposure.
PMID- 11004232
TI - Effects of retinoic acid on airspace development and lung collagen in hyperoxia
exposed newborn rats.
AB - Impaired septal formation and decreased alveolarization are often caused by
hyperoxic injury to the developing lung and are characteristic features of
bronchopulmonary dysplasia. Dexamethasone, frequently administered to infants
during oxygen exposure, also inhibits septal formation in the newborn lung.
Vitamin A administration reduces the incidence of bronchopulmonary dysplasia in
vitamin A-deficient premature infants, and retinoic acid improves alveolarization
in newborn rats treated with dexamethasone, indicating that retinoic acid may be
useful in preventing hyperoxia-induced impaired septation in bronchopulmonary
dysplasia. To investigate whether treatment with retinoic acid during exposure to
hyperoxia would improve septal formation, newborn rats exposed to > or =90% O(2)
from d 3 of life to d 14 were treated with retinoic acid (d 3-13 of life) and/or
dexamethasone (d 4-13 of life). In contrast with the effects of retinoic acid on
dexamethasone-induced inhibition of alveolarization, we found that retinoic acid
did not improve septal formation or decrease airspace size in animals exposed to
hyperoxia alone or to hyperoxia plus dexamethasone. Retinoic acid did, however,
increase collagen in airspace walls as demonstrated by staining and
immunohistochemistry. There was no increase in procollagen mRNA by Northern
hybridization analysis, indicating that retinoic acid-associated increases in
lung collagen are likely due to posttranscriptional regulation. There was a trend
toward increased survival in hyperoxia in animals treated with retinoic acid to
the extent that combined therapy with retinoic acid and dexamethasone resulted in
the greatest improvement in animal survival. These results suggest that although
retinoic acid may be of benefit in hyperoxia-induced lung injury and may have
important effects on lung matrix, it does not prevent impairment of septation or
induce alveolar formation during exposure to hyperoxia.
PMID- 11004233
TI - Noninvasive detection of changes in cerebral blood flow by near-infrared
spectroscopy in a piglet model of hydrocephalus.
AB - Formulation of rational interventions in infantile hydrocephalus is limited by
the inability to monitor cerebral hemodynamics quantitatively, continuously, and
noninvasively. Near-infrared spectroscopy (NIRS) measures changes in cerebral
concentration of oxygenated and deoxygenated hemoglobin (HbO(2) and Hb); HbD is
the derived difference between HbO(2) and Hb. Our previous work showed that HbD
reflected cerebral blood flow (CBF) measured by radioactive microspheres in a
piglet model of systemic hypotension. This study was designed to determine
whether NIRS detected important changes in cerebral perfusion and oxygenation in
a piglet model of hydrocephalus and whether changes in HbD accurately reflected
changes in CBF. Acute hydrocephalus was produced in neonatal piglets by
intraventricular infusion of "mock cerebrospinal fluid." Intracranial pressure
(ICP) was maintained for several minutes at approximately 10, 20, and 30 mm Hg
above the baseline ICP. CBF was measured in cerebral cortex, white matter, and
basal ganglia at each ICP by radioactive microspheres. Changes in HbO(2) and Hb
were measured continuously by NIRS. Cerebral perfusion pressure declined with
increasing ICP, and this decline was accompanied by significant decreases in HbD
measured by NIRS and CBF measured by radioactive microspheres. There was a strong
correlation between changes in HbD and individual changes in CBF in cerebral
cortex, white matter, and basal ganglia (all p < 0.0001). This study demonstrates
that changes in HbD reflect changes in CBF over a wide range of ICP in a model of
acute hydrocephalus. This reproducible and easily obtained measurement by NIRS
could facilitate considerably decisions concerning therapeutic interventions.
PMID- 11004234
TI - Evolution in the hypervariable region of hepatitis C virus in infants after
vertical transmission.
AB - To elucidate the clonal evolution of hepatitis C virus (HCV) during mother-to
infant transmission, we prospectively analyzed HCV clones of the hypervariable
region in four HCV RNA-positive infants and compared them with those of the
mother. Cord blood samples from three of the four infants were positive for the
HCV RNA (< or =10(3) copies/mL), and all of the four infants had the HCV RNA
titer of >10(6) copies/mL within 2 mo after birth. The hypervariable region
clones detected in the infants were closely related to those in the respective
mothers. The results suggest the perinatal transmission of HCV. The hypervariable
region clones transmitted to infants were not a single selected clone or minor
clones in the mother. None of the clones specific to the low-density fraction in
the mother was transmitted to the infants. Moreover, the proportion of HCV in the
low-density fraction was minimal in the first few months of life, but increased
several months after birth in association with the elevation of alanine
aminotransferase. These results suggest that the increase of HCV in the low
density fraction reflect the evolution of immune response in infants. We also
demonstrated that the emergence of quasispecies in infants precedes the infantile
antibody response.
PMID- 11004235
TI - Does low IgA in human milk predispose the infant to development of cow's milk
allergy?
AB - We sought a relationship between total and cow's milk-specific IgA levels in
colostrum and human milk and subsequent development of cow's milk allergy (CMA)
in the breast-fed infant. The study included 87 nursing mothers and their infants
(age, 2 d to 7 mo), followed prospectively up to 1 y. At 1 y, 48 mothers (69%
with an atopic constitution) had an infant with CMA, verified by clinical cow's
milk challenge, eight (38% with an atopic constitution) had a baby who had had
protracted infantile colic but no CMA (disease control group), and 31 (23% with
an atopic constitution) had a healthy infant. Total breast-milk IgA was measured
by radial immunodiffusion, and IgA antibodies to cow's milk were measured by
ELISA during the breast-feeding period. The levels of total and cow's milk
specific IgA antibodies in colostrum and human milk were significantly lower in
the mothers whose baby later developed CMA [estimated third day value, 0.38 g/L
(95% confidence interval, 0. 24-0.82)] than in the ones whose infant remained
healthy or had had infantile colic but not CMA [0.82 g/L (95% confidence
interval, 0. 99-1.51); p < 0.05]. The infants developed CMA significantly more
often if the concentration of total IgA antibodies in milk was <0.25 g/L, when
measured between 6 d and 4 wk postpartum [sensitivity, 0. 55; specificity, 0.92;
odds ratio, 14.7 (95% confidence interval, 3. 1-70.2); p < 0.001]. The levels of
cow's milk-specific IgA positively correlated with the levels of total IgA but
not with the development of CMA in the infant. The levels of total or cow's milk
specific IgA did not correlate with maternal atopy. IgA antibodies in colostrum
and human milk may prevent antigen entry at the intestinal surface of the breast
fed infant. A low IgA content in human milk may lead to defective exclusion of
food antigens and thus predispose an offspring to develop food allergies.
PMID- 11004236
TI - Inv(11)(p13p15) and myf-3(MyoD1) in a malignant extrarenal rhabdoid tumor of a
premature newborn.
AB - We present a premature newborn of 32 wk of gestation with a congenital malignant
extrarenal rhabdoid tumor (MERT) on the right shoulder with generalized
metastases. Standard histologic, immunohistochemical, molecular and cytogenetic
methods were used in the evaluation of diagnostic material. Biopsy of a skin
lesion showed the histologic features of a malignant rhabdoid tumor. Cytogenetic
analysis of the tumor cells revealed an inv(11)(p13p15) and additionally, an
increased expression of myf-3 (myogenic determination factor, MyoD1) and PAX3 was
detected. These results suggest an origin of the neoplasm derived from a
pluripotent cell with the potential of myogenic differentiation. Tumor suppressor
genes located on chromosome 11p13 and 11p15 may play an important role for
malignant rhabdoid tumor development and progression.
PMID- 11004237
TI - Comparative analysis of different puberty inhibiting mechanisms of two GnRH
agonists and the GnRH antagonist cetrorelix using a female rat model.
AB - GnRH agonists are the established treatment of precocious puberty caused by
premature stimulation of gonadotropin secretion. It has been reported that after
an initial stimulation ("flare-up") they reduce LH secretion by desensitization
of pituitary GnRH receptors. Little has been published about the use of GnRH
antagonists such as cetrorelix to control the onset of puberty and whether they
are potentially advantageous compared with GnRH agonists. We conducted two
multigroup experiments (12 and 10 d, respectively) treating
prepubertal/peripubertal female rats with either the GnRH agonist triptorelin or
buserelin and compared them with rats treated with the GnRH antagonist cetrorelix
and controls to assess the effects on pubertal progress and serum hormones. In
the second experiment, the effects of buserelin and cetrorelix on gene expression
of the GnRH receptor, LH-beta, FSH-beta, and the alpha subunit genes in the
pituitary were also investigated. Cetrorelix, triptorelin, and buserelin retarded
the onset of puberty as determined by delayed vaginal opening, lower ovarian
weights, and lower serum estradiol levels. However, although LH and FSH levels
were stimulated by both agonists, they were inhibited by cetrorelix. In the
cetrorelix versus buserelin experiment, pituitary gene expression of the GnRH
receptor and LH-beta subunit were significantly lower in cetrorelix treated rats
compared with controls whereas buserelin had little effect. Expression of FSH
beta and alpha subunit were stimulated by buserelin but not by cetrorelix. Even
though all three of these GnRH analogues inhibited gonadal development and
delayed the onset of puberty, the GnRH agonists had stimulating and inhibiting
effects on the pituitary-gonadal axis whereas cetrorelix exerted only inhibiting
effects. We conclude from this female rat model that cetrorelix may offer
advantages for a more controlled medical treatment of precocious puberty compared
with GnRH agonist treatment.
PMID- 11004238
TI - Validated multivariate models predicting the growth response to GH treatment in
individual short children with a broad range in GH secretion capacities.
AB - The aim of the study was to develop and validate models that could predict the
growth responses to GH therapy of individual children. Models for prediction of
the initial one and 2-y growth response were constructed from a cohort of 269
prepubertal children (Model group) with isolated GH deficiency or idiopathic
short stature, using a nonlinear multivariate data fitting technique. Five sets
of clinical information were used. The "Basic model" was created using
auxological data from the year before the start of GH treatment and parental
heights. In addition to Basic model data, the other four models included growth
data from the first 2 y of life, or IGF-I, or GH secretion estimated during a
provocation test (AITT) or a spontaneous GH secretion profile. The performance of
the models was validated by calculating the differences between predicted and
observed growth responses in 149 new GH treated children (Validation group) who
fulfilled the inclusion criteria used in the original cohort. The SD of these
differences (SD(res)) in the validation group was compared with the SD(res) for
the model group. For the 1st y, the SD(res) for the Basic model was 0.28
SDscores. The lowest SD(res) (0.19 SDscores), giving the most narrow prediction
interval, was achieved adding the 24h GH profile and data on growth from the
first 2 y of life to the Basic model. The models presented permit estimation of
GH responsiveness in children over a broad range in GH secretion, and with an
accuracy of the models substantially better than when using maximal GH response
during an provocation test. The predicted individual growth response, calculated
using a computer program, can serve as a guide for evidence-based decisions when
selecting children to GH treatment.
PMID- 11004239
TI - Physiologic predictors of lumbar spine bone mass in neonates.
AB - Dual energy x-ray absorptiometry (DXA) of the lumbar spine (LS) was measured in
201 singleton infants with birth weights from 1152 to 3970 g and gestational ages
from 27 to 42 wk. All infants were well and studied at a mean (+/-SD) of 2.1 (+/
1.6) days after birth. There were 75 Caucasian (46 males, 29 females) and 126
African American infants (58 males, 68 females). Scan acquisition of the first to
fourth lumbar vertebrae was performed with a single beam whole body scanner
(Hologic QDR 1000/W densitometer, Hologic Inc, Waltham, MA, U.S.A.) using the
infant spine mode. Scan analysis was performed with software version 4.57Q and
consistent region of interest. The SD of difference for duplicate LS scans is
<1.4% at a mean bone mineral content (BMC) of 2.14 g. Results show that LS BMC,
area, bone mineral density (BMD) increased by approximately 550%, 280% and 180%,
respectively, between 27 and 42 wk gestational age. Body mass accounted for about
70% and 55% of the variance in BMC and BMD respectively. In contrast, the
infant's length appears to be the best determinant of LS area and accounts for
about 75% of the variance in LS area. Race, gender or season has little or no
effect on LS bone mass. There was progressive increase in BMC and area from first
to fourth lumbar vertebra but BMD was significantly higher only at the fourth
lumbar vertebra. We conclude that DXA LS can be performed even in small preterm
infants. Its excellent precision, low radiation exposure and rapid scan
acquisition offers promise as a useful tool for widespread use in pediatrics. Our
data may be used as a basis for further studies in physiologic and pathologic
situations that may affect bone mineralization in infants.
PMID- 11004240
TI - Bone turnover and growth during and after continuing chemotherapy in children
with acute lymphoblastic leukemia.
AB - Children treated for acute lymphoblastic leukemia may develop reduced bone
mineral density during treatment, but there is little information on the
mechanisms involved. In a prospective, longitudinal study on 15 children with
ALL, we undertook serial measurements of markers of bone and collagen turnover,
insulin-like growth factor (IGF)-I and its binding proteins (IGFBPs)-3 and -2
during the second year of continuing chemotherapy. In eight patients we also
measured lower leg length by knemometry. Height SD scores, lower leg length
velocity, IGF-I, and markers of bone collagen turnover did not differ
significantly from healthy children. However, bone alkaline phosphatase, a marker
of the differentiated osteoblast, was lower (mean SD score, -0.64; p < 0.0001),
whereas procollagen type III N-terminal propeptide (P3NP, a marker of soft tissue
collagen turnover; mean SD score, +0.93, p < 0.05), IGFBP-3 (mean SD score,
+0.76; p < 0.01), and IGFBP-2 (mean SD score, +1.24, p = 0.01) were all higher
than in healthy children. IGFBP-3 decreased during episodes of afebrile
neutropenia (p < 0.05). Within 3 mo after completion of treatment, bone ALP
increased in all eight patients, but collagen markers showed little change. IGFBP
2 returned to normal posttreatment, but P3NP and IGFBP-3 remained significantly
elevated compared with healthy children (mean SD scores, +1.51 and +1.36,
respectively; p < 0.01). We conclude that continuing chemotherapy was associated
with normal growth and bone collagen turnover but enhanced soft tissue collagen
turnover. Bone bone alkaline phosphatase was low throughout treatment, which
suggests impaired osteoblast differentiation resulting from a direct effect of
chemotherapy on bone. Although the effect was reversible, the long-term
implications for bone health in survivors remain uncertain.
PMID- 11004241
TI - Investigation of three doses of oral insulin-like growth factor-I on jejunal
lactase phlorizin hydrolase activity and gene expression and enterocyte
proliferation and migration in piglets.
AB - In a previous study, oral IGF-I at 65 nM increased lactase phlorizin hydrolase
(LPH) activity and villus height in piglets, however, the mechanisms were
unknown. Herein, the response to a range of doses of IGF-I was investigated and
we hypothesized that LPH and villus height would respond to oral IGF-I in a dose
dependent manner. Two 14-d experiments were conducted using cesarean-derived
piglets. In experiment 1, piglets (n = 28) were fed formula containing 0, 33, 65,
or 131 nmol/L (0, 0.25, 0.5, or 1.0 mg/L) recombinant human IGF-I. In experiment
2, 5'-bromodeoxyuridine was administered to piglets fed formula alone (n = 4) or
containing 131 nmol/L IGF-I (n = 4). IGF-I did not affect body weight gain or
intestinal weight or length. Jejunal villus height and LPH activity were
significantly greater in piglets fed 131 nmol IGF-I/L than control piglets.
Villus height and lactase activity in piglets fed the 33 and 65 nmol/L IGF-I
doses were similar and intermediate between control and 131 nmol IGF-I/L. Jejunal
mRNA expression and LPH polypeptide abundance were investigated in piglets
receiving 0 or 131 nmol/L IGF-I. Steady state LPH mRNA abundance was
significantly higher (p < 0.05) in IGF-I-treated piglets. The relative abundance
of proLPH(h) was not significantly increased (p = 0.06) by IGF-I treatment.
Mucosal DNA content and DNA synthesis were greater in piglets receiving 131 nmol
IGF-I/L than control, however, enterocyte migration and mucosal protein content
were unaffected. Thus, oral IGF-I increased jejunal LPH activity and LPH mRNA
abundance and stimulated intestinal cell hyperplasia in normal piglets.
PMID- 11004242
TI - Functional characterization of the keratinocyte growth factor system in human
fetal gastrointestinal tract.
AB - Keratinocyte growth factor (KGF) is a paracrine growth factor whose mRNA has been
detected in human adult and rodent gut tissues together with its associated
receptor. Our objectives were to assess the presence of immunoreactive KGF ligand
and receptor proteins in human fetal gastrointestinal (GI) tract segments and to
evaluate the role of exogenous KGF on cell proliferation and intestinal digestive
functions. KGF (26-28 kD doublet) was identified in esophagus, stomach, small
intestine, and colon by Western blot. Its receptor (135 kD) was ubiquitously
detected in proliferative and differentiated epithelial cells of each GI segment
by use of indirect immunofluorescence (anti-bek, anti-K-sam). The addition of KGF
to explants cultured in serum-free conditions greatly stimulated DNA synthesis in
all GI tract tissues. The growth factor up-regulated intestinal sucrase
isomaltase and gamma-glutamyl-transpeptidase activities in jejunal explants,
whereas it down-regulated these activities in colon explants. It is suggested
that the KGF system likely represents an important paracrine pathway that is able
to stimulate cell proliferation in all segments of the human fetal GI tract and
to differentially regulate intestinal digestive functions.
PMID- 11004243
TI - Nonnutritive factors in colostrum enhance myofibrillar protein synthesis in the
newborn Pig.
AB - Colostrum is a complex source of nutrients, immune factors, and bioactive
substances consumed by newborn mammals. In previous work, we observed that
protein synthesis in the skeletal muscle of newborn piglets is enhanced when they
are fed colostrum rather than a nutrient-matched formula devoid of growth
factors. To elucidate the mechanisms responsible for this response, we contrasted
the fractional rates of sarcoplasmic and myofibrillar protein synthesis of
newborn piglets that received only water with those fed for 24 h with colostrum,
a nutrient-matched formula, or mature sow's milk. Compared with water, feeding
resulted in a 2.5- to 3-fold increase in total skeletal muscle protein synthesis,
and this increase was 28% greater in the colostrum-fed than either the formula-
or mature milk-fed piglets. Feeding also stimulated muscle ribosome and total
polyadenylated RNA accretion. Ribosomal translational efficiency, however, was
similar across all fed groups. The greater stimulation of protein synthesis in
colostrum-fed pigs was restricted entirely to the myofibrillar protein
compartment and was associated with higher ribosome and myosin heavy chain mRNA
abundance. Taken together, these data suggest that nonnutritive factors in
colostrum enhance ribosomal accretion and muscle-specific gene transcription
that, in turn, stimulate specifically the synthesis of myofibrillar proteins in
the skeletal musculature of the newborn.
PMID- 11004244
TI - Factors affecting the measurement of energy expenditure during energy balance
studies in preterm infants.
AB - Our objective was to examine factors that affect the accuracy of energy
expenditure measurements (EE), when using flow-through indirect calorimetry (IC),
to determine the minimum length of time needed to measure 24- and 48-h EE and to
compare cross-over and parallel designs as methods of investigation during energy
balance collections (EB) in preterm infants. A baby doll manikin was used to
determine equilibration times and to compare VCO(2) and VO(2) as measured by flow
meter and indirect calorimetry under different study conditions, one of which
simulated an EB. "Continuous" EE was measured to determine the minimum length of
time needed to accurately reflect 24- and 48-h EE and to compare parallel and
cross-over studies as methods of study design in a group of "normal" enterally
fed preterm infants. The mean (+/-SD) errors between flow meter and indirect
calorimetry determinations for VCO(2) and VO(2) were -1.9 +/- 2.5 and -1.8 +/-
4.3% under conditions that simulated an EB. Cumulative 6-h EE accurately
predicted 24- and 48-h EE. Expressed in absolute terms (kcal/d), EE did not
change on a day-to-day basis but did increase over the 2-wk study period.
Expressed on body weight basis (kcal/kg/d), EE did not change on a day-to-day or
week-to-week basis. The variance in EE due to biologic variability; i.e. the
parallel design, was approximately 6 times greater than that due to age, weight,
and weight gain; i.e. the cross-over design. Indirect calorimetry, therefore,
accurately measures EE in conditions simulating an energy balance collection. Six
hour EE determinations are valid estimate of EE during a 48-h balance collection,
while cross-over studies may be the preferred method of study design during short
term studies of EE in preterm infants.
PMID- 11004245
TI - Dietary 20:4n-6 and 22:6n-3 modulates the profile of long- and very-long-chain
fatty acids, rhodopsin content, and kinetics in developing photoreceptor cells.
AB - The objective of this study was to determine whether addition of dietary 20:4n-6
and 22:6n-3 to a conventional infant formula fat blend influences membrane long
chain and very-long-chain fatty acid composition, rhodopsin content, and
rhodopsin kinetics in developing rat photoreceptor cells. The dietary fats were
formulated based on the fat composition of a conventional infant formula
providing an 18:2n-6/18:3n-3 ratio of 7:1 (SMA, Wyeth Nutritionals), which served
as the control fat blend. This dietary fat blend was modified to contain 20:4n-6
[arachidonic acid (AA)], 22:6n-3 [docosahexaenoic acid (DHA)], AA + DHA, or an
18:2n-6/18:3n-3 ratio of 4:1 (alpha-linolenic acid). Dams were fed diets from
birth, and rat pups were fed the same diet after weaning. Retinas and rod outer
segments were prepared in the dark from pups at 2, 3, and 6 wk of age for fatty
acid analysis of individual phospholipids, rhodopsin content, and rhodopsin
disappearance kinetics after light exposure. Feeding AA + DHA in the diet
increased 22:6n-3 levels in phosphatidylcholine and phosphatidylethanolamine. In
phosphatidylcholine, total n-6 tetraenoic very-long-chain fatty acids and total n
3 pentaenoic and n-3 hexaenoic very-long-chain fatty acids increased after
feeding AA and DHA, respectively. Developmental changes were characterized by a
decrease in 20:4n-6 in the major phospholipids, whereas 22:6n-3 increased with
age in rod outer segments. The highest rhodopsin content occurred in the retina
of rats fed diets containing AA and/or DHA. The kinetics of rhodopsin
disappearance after light exposure was highest in rats fed DHA at 6 wk of age.
This study demonstrates that small manipulations of the dietary level of 20:4n-6
and 22:6n-3 are important determinants of fatty acid composition of membrane
lipid and visual pigment content and kinetics in the developing photoreceptor
cell.
PMID- 11004246
TI - Lipopolysaccharides do not alter metabolic disturbances in hippocampal slices of
fetal guinea pigs after oxygen-glucose deprivation.
AB - The aim of the present study was to clarify whether endotoxins
[lipopolysaccharides (LPS)] have a toxic effect on fetal brain tissue after
cerebral ischemia, while excluding their effect on the cardiovascular system.
Experiments were therefore performed on hippocampal slices prepared from mature
fetal guinea pigs. In particular, we studied the influence of LPS on nitric oxide
production, energy metabolism, and protein synthesis after oxygen-glucose
deprivation (OGD). Incubating hippocampal slices in LPS (4 mg/L) for as long as
12 h did not alter cGMP tissue concentrations significantly. However, 10 min
after OGD of 40-min duration, cGMP tissue concentrations were substantially
increased in relation to controls, and this increase was almost completely
blocked by the application of 100 microM N:(omega)-nitro-L-arginine, indicating
that nitric oxide synthase was activated after OGD in fetal brain tissue. Again,
LPS did not have any effect on cGMP tissue concentrations after OGD. Furthermore,
addition of LPS altered neither protein synthesis nor energy metabolism measured
12 h after OGD. We therefore conclude that, apart from their well-known influence
on the cardiovascular system, LPS do not alter metabolic disturbances in
hippocampal slices of fetal guinea pigs 12 h after OGD. A direct toxic effect of
LPS on immature brain tissue within this interval does not therefore seem to be
very likely. However, delayed activation of LPS-sensitive pathways that may be
involved in cell death, or damage limited to a small subgroup of cells such as
oligodendrocyte progenitors, cannot be fully excluded.
PMID- 11004247
TI - Three novel PHEX gene mutations in Japanese patients with X-linked
hypophosphatemic rickets.
AB - X-linked hypophosphatemic rickets (XLH) is an X-linked dominant disorder
characterized by renal phosphate wasting, abnormal vitamin D metabolism, and
defects of bone mineralization. The phosphate-regulating gene on the X-chromosome
(PHEX) that is defective in XLH has been cloned, and its location identified at
Xp22.1. It has been recognized to be homologous to certain endopeptidases. So
far, a variety of PHEX mutations have been identified mainly in European and
North American patients with XLH. To analyze the molecular basis of four
unrelated Japanese families with XLH, we determined the nucleotide sequence of
the PHEX gene of affected members. We detected a new nonsense mutation (R198X) in
exon 5, a new 3 nucleotides insertion mutation in exon 12 and a new missense
mutation (L160R) in exon 5 as well as a previously reported nonsense mutation in
exon 8 (R291X). These results suggest that: 1) PHEX gene mutations are
responsible for XLH in Japanese patients, and 2) PHEX gene mutations are
heterogeneous in the Japanese population similarly to other ethnic populations.
PMID- 11004248
TI - Temperature-sensitive mutation of PEX6 in peroxisome biogenesis disorders in
complementation group C (CG-C): comparative study of PEX6 and PEX1.
AB - Peroxisome biogenesis disorders (PBD), including Zellweger syndrome, neonatal
adrenoleukodystrophy, and infantile Refsum disease, are a group of genetically
heterogeneous autosomal-recessive diseases caused by mutations in PEX genes that
encode peroxins, proteins required for peroxisome biogenesis. Zellweger syndrome
patients present the most severe phenotype, whereas neonatal adrenoleukodystrophy
patients are intermediate and infantile Refsum disease patients have the mildest
features. PEX6 is a causative gene for PBD of complementation group C (CG-C) and
encodes the peroxin Pex6p, one of the ATPases associated with diverse cellular
activities and a member of the same family of proteins as Pex1p, a causative
protein for PBD of CG-E (CG1). Here, we identified the temperature sensitivity of
peroxisomes in the fibroblasts of a patient with neonatal adrenoleukodystrophy in
CG-C. Peroxisomes were morphologically and biochemically formed at 30 degrees C
but not at 37 degrees C. This patient was homozygous for a missense mutation, T-
>C at nucleotide 170 resulting in a change from leucine to proline at amino acid
57 (L57P) in Pex6p. CG-C cell mutants (ZP92) in the Chinese hamster ovary
transfected with L57P in HsPEX6 revealed the same temperature-sensitive
phenotype. However, PEX1-deficient Chinese hamster ovary cell mutants (ZP101)
transfected with L111P in PEX1, the counterpart to L57P in PEX6, showed no
temperature sensitivity. In addition, ZP92 transfected with G708D in PEX6, the
counterpart to the temperature-sensitive mutation G843D in PEX1, revealed no
temperature-sensitive phenotype. These results indicate that L57P in Pex6p is a
temperature-sensitive mutation causing the milder phenotype in a patient with PBD
in CG-C. They also indicate that the amino acid residues responsible for
temperature sensitivity do not seem to be conserved between Pex6p and Pex1p.
PMID- 11004250
TI - Lung water and proton magnetic resonance relaxation in preterm and term rabbit
pups: their relation to tissue hyaluronan.
AB - The present study was performed to investigate simultaneously total lung water,
T(1) and T(2) relaxation times, and hyaluronan (HA) in preterm and term rabbits.
Attempts were also made to establish the relationship of HA to total lung water
and to T(2)-derived motionally distinct water fractions. Experiments were
performed in fetal Pannon white rabbit pups at gestational ages of 25, 27, 29,
and 31 d and at a postnatal age of 4 d. Lung tissue water content (desiccation
method), T(1) and T(2) relaxation times (H(1)-NMR method), and HA concentration
(radioassay) were measured, and free and bound water fractions were calculated by
using multicomponent fits of the T(2) relaxation curves. Lung water content and
T(1) and T(2) relaxation times were highest at a gestational age of 27 d and then
declined steadily during the whole study period. Similar trends and time courses
were seen for the fast and slow components of the T(2) relaxation curve. The T(2)
derived free water fraction remained unchanged at a gestational age of 25-29 d (
approximately 67%), but increased progressively to a value of 78.5 +/- 7.9% at 31
d (p < 0. 001) and to 83.4 +/- 9.4% at the postnatal age of 4 d (p < 0.01).
Opposite changes occurred in the bound water fraction. Lung HA concentration
decreased with advancing gestation from 870.8 +/- 205.2 microg/g dry weight at 25
d to 162.6 +/- 32.4 microg/g dry weight at 31 d (p < 0.001), but it was increased
2-fold postnatally. HA correlated positively with total lung water (r = 0.39; p <
0.001) but not with the bound water fraction. It is suggested that the
physiologic lung dehydration is associated with macromolecule-related
reorganization of lung water and that the role of HA in this process needs to be
further investigated.
PMID- 11004249
TI - Relaxant effects of carbon monoxide compared with nitric oxide in pulmonary and
systemic vessels of newborn piglets.
AB - Nitric oxide (NO) has been implicated in a number of diverse physiologic
processes, including regulation of vascular tone. Carbon monoxide (CO) is another
endogenously generated diatomic gas that may play an important physiologic role
in vascular smooth muscle homeostasis. The purpose of this study was to compare
the responses to exogenous NO and CO in isolated vessels (pulmonary arteries,
pulmonary veins, and mesenteric arteries) from 12- to 24-h-old and 2-wk-old
piglets. Vessels precontracted with the thromboxane A(2) mimetic U46619 (10(-7)
M) relaxed in response to CO (2 x 10(-6) to 2 x 10(-4) M) and NO (2 x 10(-9) to 2
x 10(-7) M); these effects were not affected by endothelium removal but were
completely abolished by the soluble guanylate cyclase inhibitor ODQ (10(-5) M).
In pulmonary arteries, the maximal relaxation to NO increased with postnatal age
from 33 +/- 4% of the precontraction value to 56 +/- 5%, in 12- to 24-h-old and 2
week-old piglets, respectively (p < 0.01), but the response to CO decreased from
25 +/- 3% to 12 +/- 1%, respectively (p < 0.01). The maximal response to CO was
greater in pulmonary veins than in pulmonary or mesenteric arteries for both age
groups (p < 0.01). Vasorelaxation induced by endogenous NO (stimulated by
acetylcholine) was also greater in pulmonary veins when compared with pulmonary
arteries and increased with postnatal age in both vessels. In contrast, no age
related differences were observed in the vasorelaxation induced by the cGMP
analog 8-bromo cGMP in pulmonary arteries. When the response to NO was analyzed
under three different extracellular O(2) concentrations (PO(2) 4.51 +/- 0.03, 19.
32 +/- 0.17, and 86 +/- 0.62, kPa), no significant differences were found.
However, in the presence of superoxide dismutase (100 U/mL). the response to CO
remained unchanged, and the response to NO improved in pulmonary arteries from 2
week-old but not from newborn piglets. In conclusion, both NO and CO relaxed
neonatal vessels through soluble guanylate cyclase activation. However, when
compared with NO, CO exhibited a poor vasorelaxant activity. Pulmonary
vasorelaxation induced by NO increased with postnatal age, whereas that induced
by CO decreased. Changes in extracellular oxygen concentration did not alter the
pulmonary vascular response to NO. However, the presence of superoxide dismutase
improved the response to NO, indicating that oxidant activity limits the
vasorelaxant response to NO but not to CO.
PMID- 11004251
TI - Effects of deferoxamine, a chelator of free iron, on NA(+), K(+)-ATPase activity
of cortical brain cell membrane during early reperfusion after hypoxia-ischemia
in newborn lambs.
AB - Free iron chelation after hypoxia-ischemia can reduce free radical-induced damage
to brain cell membranes and preserve electrical brain activity. We investigated
whether chelation of free iron with deferoxamine (DFO) preserved cortical cell
membrane activity of Na(+),K(+)-ATPase and electrocortical brain activity (ECBA)
of newborn lambs during early reperfusion after severe hypoxia-ischemia. Hypoxia
was induced in 16 lambs by decreasing the fraction of inspired oxygen to 0.07 for
30 min, followed by a 5-min period of hypotension (mean arterial blood pressure
<35 mm Hg). ECBA (in microvolts) was measured using a cerebral function monitor.
Immediately after hypoxia and additional ischemia, eight lambs received DFO (2.5
mg/kg, i.v.), and seven lambs received a placebo (PLAC). Two lambs underwent sham
operation. One hundred eighty minutes after completion of hypoxia and ischemia,
the brains were obtained and frozen. Na(+),K(+)-ATPase activity was measured in
the P(2) fraction of cortical tissue. Na(+),K(+)-ATPase activity was 35.1 +/-
7.4, 42.0 +/- 7.6, and 40.7 +/- 1.4 micromol inorganic phosphate/mg protein per
hour in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p <
0.05: DFO versus PLAC). ECBA was 11.2 +/- 6.1, 14.8 +/- 4.8, and 17.5+/-.0.5
microV in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p =
0.06: DFO versus PLAC). Na(+),K(+)-ATPase activity correlated with ECBA at 180
min of reperfusion (r = 0.85, p < 0.001). We conclude that Na(+),K(+)-ATPase
activity of cortical brain tissue was higher in DFO-treated lambs compared with
PLAC-treated animals during the early reperfusion phase after severe hypoxia
ischemia, suggesting a reduction of free radical formation by DFO. Furthermore, a
positive relationship was found between Na(+),K(+)-ATPase activity and ECBA.
PMID- 11004252
TI - Esterification of vitamin A by the human placenta involves villous mesenchymal
fibroblasts.
AB - Vitamin A (retinol) and its active derivatives (retinoic acids) are essential for
growth and development of the mammalian fetus. Maternally derived retinol must
pass the placenta to reach the developing fetus. Despite its apparent importance,
little is known concerning placental transfer and metabolism of retinol, and
particularly of placental production and storage of retinyl esters. To elucidate
this metabolic pathway, we incubated, in the presence of retinol, 1) human full
term placental explants and 2) primary cultures of major cells types contributing
to placental function: trophoblasts and villous mesenchymal fibroblasts. We used
HPLC to determine the types and concentrations of retinyl esters produced by
these explants and cells. About 14% of total cellular retinol in placental
explants was esterified. The most abundant esters were myristate and palmitate.
Primary cell cultures showed that fibroblasts efficiently produced retinyl
esters, but trophoblasts did not. In both types of experiments, no retinyl esters
were detected in the culture medium, suggesting that retinyl esters were produced
for storage purpose. These results suggest that villous mesenchymal fibroblasts
are primary sites of retinol esterification and storage in the placenta.
PMID- 11004253
TI - Comparison of visual results in initial and re-treatment laser in situ
keratomileusis procedures for myopia and astigmatism.
AB - PURPOSE: To report the results of initial and re-treatment laser in situ
keratomileusis procedures for myopia and astigmatism. METHODS: A total of 1161
consecutive inital and retreatment laser in situ keratomileusis procedures in 697
patients performed between September 19, 1996, and June 20, 1998, were
retrospectively analyzed. Baseline and postoperative best spectacle-corrected
visual acuity, uncorrected visual acuity, spherical and cylindrical refractions,
computerized video keratography, and biomicroscopy were measured or performed on
each eye. RESULTS: Of 1,071 eyes, 900 (84%) underwent a single-laser in situ
keratomileusis procedure, and 171 of 1,071 eyes (16%) underwent one or two re
treatment procedures. The preoperative mean +/- SD spherical equivalent was -5.09
+/- 3.15 diopters (range, -0.75 to -14.38 diopters) and the cylinder was 0.97 +/-
1.09 diopters (range, 0.00 to 3.25 diopters) in the group that underwent a single
laser in situ keratomileusis treatment. The preoperative mean +/- SD spherical
equivalent was -6.26 +/- 3.04 diopters (range, -1.75 to -12.88 diopters) and the
cylinder was 1.53 +/- 1.11 diopters (range, 0.00 to 3.50 diopters) in the group
that underwent re-treatment. Before re-treatment, 110 eyes (64.3%) in the group
that underwent re-treatment achieved 20/40 or better uncorrected visual acuity
and 23 eyes (13.5%) achieved 20/25 or better. Three months after re-treatment,
155 eyes (90.6%) achieved 20/40 or better, and 80 eyes (46.8%) achieved 20/25 or
better. In the single-procedure group, uncorrected visual acuity at 3 months
revealed 20/40 vision or better in 856 eyes (95.1%) and 20/25 vision or better in
572 eyes (63.6%). In this study group, 23.6% of eyes with a preoperative
spherical equivalent greater than -6.0 diopters underwent re-treatment compared
with 11.8% of eyes with a preoperative spherical equivalent of -6.0 diopters or
less. CONCLUSIONS: Laser in situ keratomileusis appears to be an effective
procedure for mild, moderate, and severe myopia. In eyes with residual refractive
error, re-treatment laser in situ keratomileusis procedures can result in good
visual outcomes.
PMID- 11004254
TI - Photorefractive keratectomy for compound myopic astigmatism.
AB - PURPOSE: To evaluate the safety and efficacy of photorefractive keratectomy for
the treatment of primary compound myopic astigmatism. METHODS: In a prospective
study, 93 eyes from 56 patients with a mean spherical equivalent of -4.98 +/-
1.80 diopters (range, -1.75 to -8.5) underwent photoastigmatic refractive
keratectomy with the Summit Apex Plus excimer laser using erodible mask
technology and were followed for 2 years. Primary outcome measures included an
assessment of astigmatic correction through vector analysis, manifest refraction,
uncorrected visual acuity, corneal clarity, and the presence of adverse symptoms.
RESULTS: Eighty-five eyes (91.4%) were available for analysis at 6 months. Mean
spherical equivalent refraction was reduced 85% (mean, -0.75 +/- 0.85 diopter)
and the target-induced astigmatism was reduced 70% (mean, 0.98 +/- 1.88
diopters). Forty-eight eyes (56%) had an uncorrected visual acuity of 20/20 or
greater, whereas 70 eyes (82%) had an uncorrected visual acuity of 20/40 or
greater. Twenty-four eyes (26% ) required re-treatment because of undercorrection
of the spherical equivalent and astigmatic components after the 6-month follow
up. Fifty-nine of the remaining eyes were available at the 24-month visit. Mean
spherical equivalent refraction was reduced to -0.39 +/- 0.72 diopter (91.8%).
The target-induced astigmatism was reduced 64% from 1.74 diopters. Forty-one eyes
(81.3%) were within +/-1.0 diopter of attempted spherical equivalent correction.
Stability within a spherical equivalent of +/-0.5 diopter occurred after the
first postoperative month. Fifty-six eyes (94.9%) had an uncorrected visual
acuity of 20/40 or greater, whereas 34 eyes (57.6 %) demonstrated an uncorrected
visual acuity of 20/20 or greater. One eye (1.7%) lost 2 or more lines of best
spectacle-corrected visual acuity. CONCLUSION: Photoastigmatic refractive
keratectomy with the Summit Apex Plus excimer laser is a safe and effective
method of reducing compound myopic astigmatism. However, higher re-treatment
rates may result from significant undercorrections because of current laser
algorithms and variability in the mean angle of error.
PMID- 11004255
TI - The effectiveness of a topical antibiotic irrigating solution in a model of
staphylococcal keratitis after lamellar keratectomy.
AB - PURPOSE: To create a model of Staphylococcus aureus keratitis after lamellar
keratectomy; to assess the toxicity of an antibiotic irrigating solution on the
corneal stromal bed; and to test the chemotherapeutic effectiveness of a topical
antibiotic, both alone and with an antibiotic-containing irrigating solution in
preventing S. aureus keratitis after lamellar keratectomy. METHODS: The right eye
of each of 38 rabbits were used in this study. In 18 eyes, a lamellar flap was
created with a microkeratome, and an inoculum of S. aureus (either 1,000, 5,000,
or 50,000 CFUs) was instilled under each flap; the eyes were examined for signs
of infection and inflammation at 24 and 48 hours. In another five eyes, a
lamellar flap was created in the same manner and the stromal bed was irrigated
with 0.3% ofloxacin; the eyes were assessed for ocular inflammatory changes and
evidence of crystalline deposits. Finally, in each of 15 additional eyes, 1,000
CFUs of S. aureus were instilled under a lamellar flap to create experimental
infectious keratitis. The keratitis was treated according to three regimens:
irrigation of the stromal bed with sterile balanced salt solution; irrigation of
the stromal bed with 0.3% ofloxacin, followed by application of topical ofloxacin
four times a day; application of topical ofloxacin only, four times a day. Eyes
were examined for infection and ocular inflammatory changes at 24 and 48 hours.
RESULTS: Staphylococcus aureus keratitis can consistently be produced under the
stromal flap by inoculation of relatively few organisms. Irrigation of the
stromal bed with commercial-strength topical ofloxacin does not appear to be
toxic to the stromal bed, with no evidence of crystalline precipitates of the
antibiotic. In our model of infectious keratitis after lamellar keratectomy, both
topical ofloxacin alone and the combination of topical ofloxacin and irrigation
of the stromal bed with 0.3% ofloxacin were effective at preventing S. aureus
keratitis. However, the combined treatment of antibiotic irrigation plus topical
antibiotic was more effective at preventing inflammation than topical ofloxacin
alone. CONCLUSIONS: In this model of S. aureus keratitis after lamellar
keratectomy, irrigation of the stromal bed with antibiotic plus topical
antibiotic appears to be both safe and effective for preventing infection.
PMID- 11004256
TI - Gas-permeable scleral contact lens therapy in ocular surface disease.
AB - PURPOSE: To describe the therapeutic benefits of nonfenestrated gas-permeable
scleral contact lenses in the management of patients with ocular surface disease.
METHODS: The charts of 49 consecutive patients (76 eyes) with ocular surface
disease whose management included the use of gas-permeable scleral contact lenses
were reviewed. We also developed a questionnaire to assess the impact of lens
wear on subjective aspects of activities of daily living. RESULTS: The mean age
of the 49 patients was 44.6 years (range, 3 to 87 years); 31 patients were female
and 18 were male. The most common indication for fitting of the lenses was
Stevens-Johnson syndrome (54 [71%] of the 76 eyes). Other indications included
ocular cicatricial pemphigoid, exposure keratitis, toxic epidermal necrolysis,
postherpetic keratitis, congenital deficiency of meibomian glands, superior
limbal keratoconjunctivitis, Sjogren syndrome, and inflammatory corneal
degeneration. The mean follow-up was 33.6 months (range, 2 to 144 months).
Improvement in best-corrected visual acuity (defined as a gain of 2 or more
Snellen lines) was observed in 40 (53%) of the eyes. In eight (53%) of the 15
eyes with active corneal epithelial defects at the time of lens fitting, the
defects healed, whereas in the remaining seven eyes the corneal epithelial
defects remained unchanged. Forty-five (92%) of the 49 patients reported
improvement in their quality of life as a result of reduction of photophobia and
discomfort. The mean wearing time of the gas-permeable scleral contact lenses was
13.7 hours per day (range, 4 to 18 hours). Many patients had preparatory surgical
procedures before lens fitting (for example, punctal occlusion or mucous membrane
grafting), and some had visual rehabilitation surgical procedures (for example,
keratoplasty and/or cataract surgery) after lens fitting. CONCLUSIONS: Gas
permeable scleral contact lens wear provides an additional effective strategy in
the surface management and visual rehabilitation of patients with severe ocular
surface disease.
PMID- 11004257
TI - Treatment of persistent corneal epithelial defect with extended wear of a fluid
ventilated gas-permeable scleral contact lens.
AB - PURPOSE: To report treatment of persistent corneal epithelial defects
unresponsive to other therapies by extended wear of a fluid-ventilated gas
permeable scleral contact lens. METHODS: In this retrospective study, 14 eyes of
13 consecutive patients referred for the treatment of persistent corneal
epithelial defects that failed to heal with conventional therapies or developed
epithelial defects after penetrating keratoplasty for persistent corneal
epithelial defects were fitted with an extended-wear gas-permeable scleral lens.
These included seven eyes of six patients with Stevens-Johnson syndrome and seven
eyes of seven patients who did not have Stevens-Johnson syndrome. Twelve eyes had
undergone recent penetrating keratoplasty. All 14 eyes were fitted with a gas
permeable scleral contact lens designed to avoid the intrusion of air bubbles
under its optic. An antibiotic and corticosteroid were added to the lens fluid
reservoir or instilled before each lens insertion in 12 of 14 eyes. The lenses
were worn continuously except for brief periods of removal for purposes of
cleaning, replacement of the lens fluid reservoir, and examination and
photography of the cornea. RESULTS: Five of the seven persistent corneal
epithelial defects associated with Stevens-Johnson syndrome healed. The
persistent corneal epithelial defects of four of these eyes re-epithelialized
within 7 days, and a fifth healed in 27 days of gas-permeable scleral lens
extended wear. A sixth persistent corneal epithelial defect that failed to heal
initially re-epithelialized after a subsequent penetrating keratoplasty and gas
permeable scleral lens extended wear. The seventh eye healed after 3 days of gas
permeable scleral lens extended wear, but the persistent corneal epithelial
defect subsequently recurred. Three of seven non-Stevens-Johnson syndrome
persistent corneal epithelial defects re-epithelialized within 36 hours, 6 days,
and 36 days, respectively. Of the six (six of 14) persistent corneal epithelial
defects that failed to heal with a gas-permeable scleral lens extended wear, one
subsequently healed after multiple amniotic membrane grafts. Microbial keratitis
occurred in four eyes (four of 14) and graft failure in one eye, all of which
required repeat penetrating keratoplasty. CONCLUSION: Extended wear of an
appropriately designed gas-permeable scleral contact lens was effective in
promoting the healing of persistent corneal epithelial defects in some eyes that
failed to heal after other therapeutic measures. Re-epithelialization appears to
be aided by a combination of oxygenation, moisture, and protection of the fragile
epithelium afforded by the scleral lens. However, microbial keratitis represents
a significant risk.
PMID- 11004258
TI - Outcome of probing for congenital nasolacrimal duct obstruction in older
children.
AB - PURPOSE: To evaluate the role of probing in congenital nasolacrimal duct
obstruction in children age 2 years and older and to establish factors predictive
of the outcome. METHODS: The study was a single-center, prospective,
interventional case series. Sixty patients with congenital nasolacrimal duct
obstruction aged 24 months or older (range, 24 to 186 months; median, 33 months)
presenting consecutively to the authors' institutional referral practice were
studied. Probing of the nasolacrimal system under general anesthesia was the
surgical intervention. Success of probing was the main outcome measure. Success
was predefined as complete resolution of symptoms and signs (tearing, crusting,
discharge, regurgitation on pressure over the lacrimal sac) of congenital
nasolacrimal duct obstruction within 3 weeks of the procedure and continued
remission at 6 months. Two attempts at probing were necessary before the
procedure was declared a failure. RESULTS: One attempt at probing resulted in
resolution in 73.3% (44 of 60) patients. Sixteen patients needed a repeat
procedure. The overall success rate was 80% (48 of 60). Two specific types of
obstructions of the nasolacrimal duct were recognized on probing: membranous and
firm. Factors predictive of failure of probing were age older than 36 months (P
<.0001); bilateral affection (P =.012); failed conservative therapy (P =.015);
failed earlier probing (P <.0001); dilated lacrimal sac (P <.0001); and firm
obstruction (P <.0001). CONCLUSION: Results indicate that probing is a viable
primary surgical option for congenital nasolacrimal duct obstruction in children
who present between 2 and 3 years of age, and identify factors predictive of poor
prognosis.
PMID- 11004259
TI - Immune-recovery uveitis in patients with cytomegalovirus retinitis taking highly
active antiretroviral therapy.
AB - PURPOSE: To investigate the clinical features associated with immune recovery in
human immunodeficiency virus (HIV)-infected patients with cytomegalovirus
retinitis who are taking highly active antiretroviral therapy. METHODS: Sixteen
patients were evaluated prospectively at the National Eye Institute, Bethesda,
Maryland. Evaluation included a medical history and a complete ophthalmologic
examination. The examination included best-corrected visual acuity score measured
by means of logarithmic charts, slit-lamp biomicroscopy, dilated retinal
examination, retinal photography, and fluorescein angiography. Immune-recovery
uveitis was defined as the ocular inflammation associated with clinical immune
recovery in patients taking potent antiretroviral regimens. The ophthalmic
characteristics of immune-recovery uveitis were identified, and their effect on
visual acuity was statistically analyzed. RESULTS: The mean CD4+ T-lymphocyte
count for the 16 patients taking highly active antiretroviral therapy at the time
of evaluation was 393 cells/microl (range, 97-1,338 cells/microl). Immune
recovery uveitis was characterized by vitreitis and optic disk and macular edema.
Clinically important complications of immune-recovery uveitis included cataract
and epiretinal membrane formation. The visual acuity scores were significantly
worse in the 23 eyes with cytomegalovirus retinitis (mean, 67.2 letters, 20/50)
than in the nine eyes without cytomegalovirus retinitis (mean, 89.8 letters,
20/16) (P <.001). Regression analysis showed that a lower visual acuity score was
associated with the presence of moderate to severe macular edema on fluorescein
angiography and vitreous haze (P < or =. 001). CONCLUSIONS: Immune-recovery
uveitis is an important cause of visual morbidity in HIV-infected patients with
cytomegalovirus retinitis in the era of highly active antiretroviral therapy.
Although immune recovery associated with highly active antiretroviral therapy has
allowed some patients to discontinue specific anticytomegalovirus therapy, the
rejuvenated immune response can be associated with sight-threatening
inflammation.
PMID- 11004260
TI - Long-term posterior and anterior segment complications of immune recovery uveitis
associated with cytomegalovirus retinitis.
AB - PURPOSE: To identify and describe long-term posterior and anterior segment
complications of immune recovery uveitis in patients with inactive
cytomegalovirus retinitis who are undergoing highly active antiretroviral therapy
mediated recovery of immune function. METHODS: A prospective cohort study at a
university medical center. Twenty-nine eyes of 21 patients with immune recovery
uveitis and inactive cytomegalovirus retinitis were followed for 14.5 to 116
weeks (median, 43 weeks) after diagnosis of immune recovery uveitis. RESULTS:
Nine eyes of nine patients developed visually important complications involving
the posterior segment, anterior segment, or a combination of both. Posterior
segment complications included severe proliferative vitreoretinopathy in three
eyes and spontaneous vitreous hemorrhage from avulsion of a blood vessel
secondary to contraction of the inflamed vitreous in one eye. Proliferative
vitreoretinopathy recurred in all cases after surgery, severely compromising the
visual outcome. Anterior segment complications included posterior subcapsular
cataracts with vision decrease in five eyes and persistent anterior chamber
inflammation after cataract extraction, resulting in posterior synechiae and
large visually important lens deposits in three eyes. CONCLUSION: Persistent
inflammation in immune recovery uveitis may lead to vision-threatening
complications, such as proliferative vitreoretinopathy, posterior subcapsular
cataracts, and severe postoperative inflammation. Immune recovery uveitis is a
chronic inflammatory syndrome that may result in complications months to years
after the onset of inflammation.
PMID- 11004261
TI - Three-dimensional observations of developing macular holes.
AB - PURPOSE: To describe the morphologic features of idiopathic macular holes and
vitreous traction during macular hole evolution. METHODS: We prospectively
examined 89 eyes of 82 patients with idiopathic macular holes (stage 1, 15 eyes;
stage 2, 16 eyes; stage 3, 50 eyes; stage 4, eight eyes) using optical coherence
tomography. In addition to optical coherence tomography, scanning laser
ophthalmoscopy was performed in all 15 eyes with stage 1 hole, six of 16 eyes
with stage 2, and 19 of 50 eyes with stage 3. RESULTS: In stage 1 eyes, optical
coherence tomography revealed retinal split or cystic changes at the fovea in 11
of 15 eyes (73%) and foveal retinal detachment in four eyes (27%). Two eyes with
foveal cysts progressed to stage 2, and one developed a stage 3 hole. In one eye
with retinal detachment, the detached retina thinned and developed dehiscence.
Optical coherence tomography showed a vitreous cortex that was detached in the
perifoveal area but attached on the fovea in 11 of the 15 stage 1 eyes. In stage
2 macular holes, retinal tissue extending from the perifoveal retina formed a
flap. Scanning laser ophthalmoscopy demonstrated intraretinal radiating striae,
which corresponded to a foveal cyst or perifoveal cystic changes. CONCLUSIONS:
Macular holes start as retinal splits or foveal cysts in most cases. The anterior
wall of the cyst serves as a flap in stage 2 and an operculum in stage 3 holes.
Radiating striae correspond to retinal splits or cysts and presumably represent
an elevation of Henle fiber. In a few macular holes, foveal detachment is the
initial change. The detached retina thins and eventually develops a hole. In both
courses, anterior traction of the slightly detached vitreous cortex appears to be
a major contributing factor to macular hole formation.
PMID- 11004262
TI - Scleral outfolding for macular translocation.
AB - PURPOSE: To report experimental study and clinical observation of scleral
outfolding for macular translocation. METHODS: In six human cadaver eyes,
circumferential mattress sutures to create sclera infoldings were compared with
radial-interrupted mattress sutures to create scleral outfoldings. In a 75-year
old man with macular degeneration and choroidal neovascular membrane, radial
interrupted mattress sutures were used for macular translocation. RESULTS: In the
human cadaver eyes, circumferential mattress sutures for scleral infolding
created an average decrease in corresponding internal anteroposterior retinal
contour of 0.36 mm. Radial-interrupted mattress sutures for scleral outfoldings
created an average decrease in the corresponding internal anteroposterior retinal
contour of 4. 61 mm. The statistical significance of the difference between
infoldings of the sclera versus outfoldings of the sclera had a P value of.0001.
CONCLUSIONS: Initial experimental and clinical study suggests that radial
interrupted mattress sutures may generate more shortening of the internal scleral
surface and greater macular translocation than circumferential mattress sutures.
Additional studies are needed to evaluate the long-term effects of radial
interrupted mattress sutures and macular translocation for treatment of subfoveal
choroidal neovascularization secondary to age-related macular degeneration.
PMID- 11004263
TI - Erbium:YAG laser vitrectomy: clinical results.
AB - PURPOSE: To evaluate the intraoperative use of a new erbium:yttrium aluminum
garnet (YAG) laser vitrectomy system. METHODS: An erbium:YAG laser combined with
an infusion-suction system (Wavelight Laser Technology, Erlangen, Germany),
equipped with a flexible fiber optic and a hand piece with a 20-gauge end tip and
a side opening of 0.6 mm was used. Cutting rates were 2 to 30 Hz, and energies
were 20 to 40 mJ. Between January 1998 and January 1999 the erbium:YAG laser
system was used in 67 consecutive patients (68 eyes) where vitrectomy was
indicated. The patients had a complete eye examination before surgery and
postoperatively at 1 to 3 days, 1 week, 3 weeks, and 6 weeks. During surgery, the
total time needed for vitrectomy, the laser time itself, amount of energy used,
cutting rate, suction, and perfusion, as well as manipulative difficulties and/or
complications, were documented. RESULTS: The average laser time was 4.5 minutes
for a basic vitrectomy with a setting of 20 mJ, 20 Hz, and suction 100 to 200 mm
Hg. Hemorrhages, loose intravitreal, and preretinal membranes of different
densities were cut well with adjustment of energy. After a minimal observation
time of 6 months (median, 12.7 months) no laser-associated complications were
found. CONCLUSIONS: The erbium:YAG laser, combined with an infusion-suction
system, offers a new technology for vitreous surgery. Its advantages, compared
with mechanical vitrectomy cutters, are higher cutting rates and the modulation
of energy. Modifications of the end tip are needed to develop this system
further.
PMID- 11004264
TI - Elevated vitreous nitric oxide levels in patients with proliferative diabetic
retinopathy.
AB - PURPOSE: The aim of this study was to determine nitric oxide levels in the
vitreous of patients with proliferative diabetic retinopathy. METHODS: Using the
spectrophotometric method based on Griess reaction, we measured levels of
nitrite, the stable product of nitric oxide, in the vitreous of 21 eyes of 21
patients who underwent vitrectomy for the treatment of proliferative diabetic
retinopathy with tractional retinal detachment, prospectively. Three samples were
excluded from the study because of blood contamination. The control group was
made up of vitreous samples from 15 eyes of 15 normal cadavers and five eyes of
five patients who were undergoing vitrectomy for macular hole surgery. RESULTS:
Nitrite levels were 0. 524 +/- 0.27 microM and 0.383 +/- 0.17 microM in the
vitreous of patients with proliferative diabetic retinopathy of diabetes type I
and type II, respectively. In 15 cadaver eyes and five vitreous samples from
patients who underwent macular hole surgery, nitrite levels were below the
detection limit (less than 0.08 microM). There was no significant difference
between nitrite levels in patients with type I and type II diabetes (P =.56),
whereas there was a significant difference between diabetes groups and controls
(P <. 00001). CONCLUSION: Vitreous nitric oxide levels are elevated in patients
with proliferative diabetic retinopathy with tractional retinal detachment.
Nitric oxide may play a role in the pathogenesis of proliferative diabetic
retinopathy.
PMID- 11004265
TI - Appearance of the optic disk and retinal nerve fiber layer in atherosclerosis and
arterial hypertension: an experimental study in rhesus monkeys.
AB - PURPOSE: To evaluate changes in the appearance of the optic nerve head and
retinal nerve fiber layer of rhesus monkeys with chronic arterial hypertension
and atherosclerosis. METHODS: Color stereoscopic fundus photographs of 25 eyes of
25 rhesus monkeys (mean age +/- SD of 20.4 +/- 1.87 years) with chronic
experimental systemic arterial hypertension and atherosclerosis (for a mean
duration of 89.1 +/- 39.1 months and 104.6 +/- 62.2 months, respectively) were
morphometrically evaluated. They were compared with color stereoscopic fundus
photographs of 17 eyes of 17 normal monkeys (mean age +/- SD of 19.76 +/- 2.19
years) without any detectable systemic or ocular disease. There was no
significant difference in age between the two study groups (P =.22). RESULTS: In
the atherosclerotic-arterial hypertensive group, visibility of the retinal nerve
fiber layer was significantly (35.691 +/- 5.95 units vs 28.72 +/- 9.18 units, P
=.009) less and frequency of localized retinal nerve fiber layer defects was
significantly (six of 25 or 24% vs zero of 17 or 0%, P =.01) more than in the
normal control group. The two groups did not differ significantly in size of the
neuroretinal rim (P =.66), shape of the neuroretinal rim (P >.15), size of alpha
(P >.44) and beta (P >.65) zones of parapapillary chorioretinal atrophy, or
regional distribution of alpha and beta zones (P >.40). CONCLUSIONS: Chronic
experimental arterial hypertension and atherosclerosis do not markedly change the
size and shape of the neuroretinal rim or parapapillary atrophy; however, they do
lead to reduced visibility of the retinal nerve fiber layer, with localized
retinal nerve fiber layer defects indicating optic nerve damage. Thus, unlike
glaucomatous optic neuropathy, experimental arterial hypertension and
atherosclerosis are not associated with a significant change in the parapapillary
atrophy or the neuroretinal rim of the optic disk despite the loss of nerve
fibers.
PMID- 11004266
TI - Plaque radiotherapy for management of ciliary body and choroidal melanoma with
extraocular extension.
AB - PURPOSE: To report the results of plaque radiotherapy of ciliary body and
choroidal melanoma with extraocular extension. METHODS: This retrospective study
of 17 eyes of 17 patients with ciliary body and choroidal melanoma demonstrated
extraocular extension that was clinically evident but less than 3 mm in
thickness. In 14 eyes, the extraocular extension was located anteriorly and in
three posteriorly. The outcome of plaque radiotherapy in terms of intraocular and
extraocular tumor responses and the development of metastasis were analyzed.
RESULTS: At a median follow-up of 63 months (range, 23 to 164 months) after
plaque radiotherapy, all patients showed control of both the intraocular and
extraocular components of ciliary body and choroidal melanoma. In no case did the
intraocular or extraocular portion of the tumor relapse. The initial median
thickness of the intraocular component was 4.9 mm, and the final median thickness
was 2.4 mm. The initial median thickness of the extraocular component was 2.0 mm,
and the final median thickness was 1.0 mm. The initial median basal diameter of
the extraocular component was 3.5 mm, and the final median basal diameter was 2.0
mm. Of 17 patients, 11 (10 with anterior and one with posterior extraocular
extension) showed partial regression in base and thickness of the extraocular
extension, and in six there was little or no change. In those with anterior
extrascleral extension, the sclera remained intact without clinically observable
necrosis, and the scleral fibers were gradually more visible as the tumor
regressed. Three patients (18%) died of metastatic melanoma at a median interval
of 38 months after plaque radiotherapy. CONCLUSIONS: Plaque radiotherapy appears
to be a reasonable treatment option for selected cases of ciliary body and
choroidal melanoma with clinically visible extraocular extension less than 3 mm
in thickness.
PMID- 11004267
TI - Immune recovery uveitis.
PMID- 11004268
TI - Axenfeld-Rieger syndrome in the age of molecular genetics.
AB - PURPOSE: To review the molecular genetics of Axenfeld-Rieger syndrome and related
phenotypes and to discuss how this information might affect the way that we
classify these disorders. METHODS: A review of historical and recent literature
on Axenfeld-Rieger syndrome and related disorders. The review includes clinical
and molecular genetic literature relevant to these phenotypes. RESULTS: Three
chromosomal loci have recently been demonstrated to link to Axenfeld-Rieger
syndrome and related phenotypes. These loci are on chromosomes 4q25, 6p25, and
13q14. The genes at chromosomes 4q25 and 6p25 have been identified as PITX2 and
FKHL7, respectively. Mutations in these genes can cause a wide variety of
phenotypes that share features with Axenfeld-Rieger syndrome. Axenfeld anomaly,
Rieger anomaly, Rieger syndrome, iridogoniodysgenesis anomaly,
iridogoniodysgenesis syndrome, iris hypoplasia, and familial glaucoma
iridogoniodysplasia all have sufficient genotypic and phenotypic overlap that
they should be considered one condition. CONCLUSIONS: Axenfeld-Rieger syndrome is
a term that can be used to describe a variety of overlapping phenotypes. To date,
at least three known genetic loci can cause these disorders. The single most
important feature of these phenotypes is that they confer a 50% or greater risk
of developing glaucoma. Currently there is a fairly arbitrary grouping of
disorders into small categories. Considering all of these phenotypes under the
heading of Axenfeld-Rieger syndrome will allow easier communication between
clinicians and scientists and eliminate arbitrary and confusing
subclassification.
PMID- 11004270
TI - Surgical debulking of eyelid and anterior orbital plexiform neurofibromas by
means of the carbon dioxide laser.
AB - PURPOSE: To present the carbon dioxide laser as an effective tool for surgical
debulking of eyelid and orbital neurofibromas. METHOD: Two patients with
neurofibromatosis underwent surgical debulking of their eyelid and orbital
plexiform neurofibromas by means of the carbon dioxide laser. RESULTS: Acceptable
cosmetic results were obtained with the removal of eyelid and orbital
neurofibromas with improved hemostasis and minimal destruction of surrounding
tissue when compared with conventional methods of removal. CONCLUSIONS: The
carbon dioxide laser may allow significant improvement in the removal of
plexiform neurofibromas.
PMID- 11004269
TI - Blepharoptosis surgery complicated by late suture migration.
AB - PURPOSE: To report late suture migration as a complication of blepharoptosis
surgery. METHOD: Case reports. RESULTS: After upper eyelid blepharoptosis repair,
two eyes of two patients developed unusual foreign body reactions and ulceration
in the conjunctiva caused by migration of nonabsorbable suture from the levator
aponeurosis to the upper conjunctival fornix. The foreign body caused eyelid
edema, papillary changes in the upper tarsal conjunctiva, recurrent
blepharoptosis, and a foreign body sensation that started more than 3 months
after the surgery and persisted until the suture was removed. The sutures, hidden
in edematous conjunctiva of the superior fornix, eluded detection. CONCLUSIONS:
Foreign body reaction secondary to suture migration is an uncommon complication
of blepharoptosis repair.
PMID- 11004271
TI - Q118X mutation of M1S1 gene caused gelatinous drop-like corneal dystrophy: the
P501T of BIGH3 gene found in a family with gelatinous drop-like corneal
dystrophy.
AB - PURPOSE: To analyze BIGH3 and M1S1 genes in two Japanese brothers with gelatinous
drop-like corneal dystrophy and five unaffected family members. METHODS: DNA was
extracted, and each part of the two genes was amplified and directly sequenced.
RESULTS: On the BIGH3 gene, a heterozygous P501T mutation was found in the elder
brother and three unaffected family members. On the M1S1 gene, both brothers with
gelatinous drop-like corneal dystrophy showed a homozygous Q118X mutation,
whereas all unaffected members were heterozygous. CONCLUSIONS: The Q118X mutation
of M1S1 gene caused gelatinous drop-like corneal dystrophy. Although the P501T of
the BIGH3 gene found in this pedigree was precisely the one reported for lattice
corneal dystrophy IIIA, no clinical feature was shown, even in the 85-year-old
father. This fact shows that the P501T mutation for LCDIIIA has low penetrance.
PMID- 11004272
TI - Marginal keratitis: an uncommon form of topical dorzolamide allergy.
AB - PURPOSE: To report a case of marginal keratitis resulting from topical
dorzolamide hypersensitivity. METHOD: Case report. RESULTS: A 68-year-old woman
presented with bilateral marginal keratitis 2 weeks after commencing bilateral
topical dorzolamide. One week after discontinuation of topical dorzolamide, the
patient was asymptomatic with complete resolution of corneal infiltrates.
CONCLUSIONS: Topical dorzolamide may cause a hypersensitivity reaction in the
form of marginal keratitis. Discontinuation of the offending medication should
result in complete resolution.
PMID- 11004273
TI - Surgical management of recurrent iris stromal cyst.
AB - PURPOSE: To report the clinical history and surgical management of recurrent
congenital iris stromal cyst. METHOD: Case report. Argon laser
endophotocoagulation and cryotherapy were used to treat a recurrent iris stromal
cyst in an 18-month-old boy. RESULTS: At 43 months of follow-up, there was no
recurrence or evidence of epithelial ingrowth. CONCLUSION: Treatment with argon
laser endophotocoagulation and cryotherapy resulted in complete resolution of a
recurrent congenital iris cyst.
PMID- 11004274
TI - Acute angle-closure glaucoma after albuterol nebulizer treatment.
AB - PURPOSE: To report acute angle-closure glaucoma associated with albuterol
nebulizer treatment. METHODS: Case report and review of the relevant literature.
RESULTS: In a 75-year-old woman with asthma, acute angle-closure glaucoma in the
right eye was probably caused by local absorption of albuterol after nebulizer
administration. CONCLUSION: As albuterol is widely used in the management of
patients with asthma, increased awareness by health care professionals of the
potential for acute angle-closure glaucoma secondary to albuterol may decrease
the incidence of this complication.
PMID- 11004275
TI - Ultrasound biomicroscopy in the diagnosis and management of pars planitis caused
by caterpillar hairs.
AB - PURPOSE: To report the use of ultrasound biomicroscopy in the detection of
caterpillar hairs in the pars plana in a patient with unilateral pars planitis.
METHOD: Ultrasound biomicroscopic imaging of the anterior segment of the eye.
RESULTS: Ultrasound biomicroscopy located a hair in the posterior chamber at the
first visit and five more in the pars plana 1 month later. This finding was
confirmed intraoperatively. CONCLUSION: Ultrasound biomicroscopy is useful in the
diagnosis and management of unilateral pars planitis of uncertain cause.
PMID- 11004276
TI - Ocular side-effects from systemic HPMPC (Cidofovir) for a non-ocular
cytomegalovirus infection.
AB - PURPOSE: To report a case of anterior uveitis and ocular hypotony during HPMPC
treatment of a cytomegalovirus infection without ophthalmic involvement. METHODS:
A 61-year-old bisexual white man with AIDS presented with moderate anterior
uveitis and ocular hypotony after 8 weeks of intravenous HPMPC and oral
probenecid co-treatment of a presumed recurrence of cytomegalovirus encephalitis.
RESULTS: There was no evidence of an ocular cytomegalovirus infection. Cidofovir
related uveitis was diagnosed, and the HPMPC-probenecid co-treatment was switched
to ganciclovir monotherapy. The ocular inflammation was successfully managed with
topical steroids and mydriatics. CONCLUSIONS: This description of ophthalmic side
effects from systemic HPMPC in the absence of ocular cytomegalovirus infection
supports the hypothesis that anterior uveitis and ocular hypotony result from a
direct interaction between the drug and the ciliary body.
PMID- 11004277
TI - Labial adenocarcinoma after treatment with cyclosporin a in a patient with
panuveitis.
AB - PURPOSE: To report a case of labial basal cell adenocarcinoma in a patient with
uveitis on treatment with cyclosporin A. METHOD: Case report. A 73-year-old woman
with panuveitis and retinal vasculitis presented with a lump on her lip after 52
months of treatment with cyclosporin A. RESULT: Excision biopsy showed a labial
adenocarcinoma. CONCLUSION: Malignancy can occur after long-term cyclosporin A
treatment for uveitis.
PMID- 11004278
TI - Acute megakaryoblastic leukemia in Down syndrome: orbital infiltration.
AB - PURPOSE: To describe an uncommon ocular presentation of acute megakaryoblastic
leukemia in a child with Down syndrome. METHOD: Case report. Initial
manifestation of disease was bilateral proptosis with secondary exposure
keratitis caused by leukemic infiltration of the orbits. RESULTS: Bone marrow
biopsy and immunophenotyping established the diagnosis of acute megakaryoblastic
leukemia (FAB-M7). The leukemia was treated successfully with chemotherapy, with
resolution of proptosis. The patient remained in remission more than 1 year after
cessation of treatment. CONCLUSIONS: Bilateral proptosis can be a presenting sign
of acute megakaryoblastic leukemia, a malignancy associated with Down syndrome.
PMID- 11004279
TI - Dot-and-fleck retinopathy in Alport syndrome caused by a novel mutation in the
COL4A5 gene.
AB - PURPOSE: To describe an unusual form of dot-and-fleck retinopathy in a slower
progressive form of X-linked Alport syndrome, caused by a novel missense mutation
in the COL4A5 gene. METHOD: Ophthalmic examination, polymerase chain reaction,
and single-strand conformational polymorphism analysis of genomic DNA were
performed in the proband. RESULTS: Ophthalmoscopy revealed classic dot-and-fleck
retinopathy but located in an unusual site. A novel COL4A5 gene mutation changing
glycine to cysteine at 177 was identified. CONCLUSIONS: Although there is no
correlation between mutation site and the resulting phenotype in Alport syndrome,
our findings suggest that further novel mutations and different ocular
manifestations may be associated with Alport syndrome.
PMID- 11004280
TI - Optical coherence tomography patterns of choroidal osteoma.
AB - PURPOSE: To determine the optical coherence tomographic images that are commonly
observed in eyes with choroidal osteoma (choroidal ossification). METHODS: Three
patients with choroidal osteoma were examined by optical coherence tomography.
RESULTS: We found two optical coherence tomographic patterns in the eyes with
choroidal osteoma. First, multiple tracks of high refractivity were present
posterior to the tumor lesion. Second, thick and irregular plate-like, high
signal intensity areas were present in the choroid in the region of the tumor.
CONCLUSIONS: Optical coherence tomography can be useful in the diagnosis of
choroidal osteoma.
PMID- 11004282
TI - Abstracts
PMID- 11004281
TI - Amniotic membrane transplantation in acute chemical and thermal injury.
AB - PURPOSE: To present a case of chemical injury and a case of thermal injury
treated by amniotic membrane transplantation in acute phase. METHODS: Case
reports. An eye with sodium hydroxide injury, opaque cornea, and limbal ischemia
of more than 180 degrees and an eye with hot tea injury, opaque cornea, stromal
edema, and scarring were treated by amniotic membrane transplantation within the
first few weeks of injury. RESULTS: In the eye with sodium hydroxide injury, 4
months after amniotic membrane transplantation, the ocular surface is stable,
superficial corneal scarring with vascularization is present, and visual acuity
is 20/25. In the eye with thermal injury, 6 months after amniotic membrane
transplantation, the ocular surface is stable, but there is superficial scarring
and vascularization, and visual acuity is 20/20. CONCLUSIONS: Amniotic membrane
transplantation can be considered in chemical injury with severe limbal ischemia
and in severe thermal injury in acute phase. Long-term studies are warranted to
evaluate further the efficacy of amniotic membrane transplantation in these
clinical situations.
PMID- 11004284
TI - Abstracts
PMID- 11004283
TI - Abstracts
PMID- 11004286
TI - Abstracts
PMID- 11004285
TI - Abstracts
PMID- 11004287
TI - Long-term intraocular pressure-lowering efficacy and safety of timolol maleate
gel-forming solution 0.5% compared with Timoptic XE 0.5% in a 12-month study.
AB - PURPOSE: To evaluate the long-term intraocular pressure-lowering efficacy and
safety of timolol maleate gel-forming solution 0.5% (Timolol GFS 0.5%, Alcon
Research Ltd, Fort Worth, Texas) compared with Timoptic XE 0.5% (Merck, Inc, West
Point, Pennsylvania) in patients with open-angle glaucoma or ocular hypertension.
METHODS: Two hundred forty-one patients with open-angle glaucoma or ocular
hypertension, who had intraocular pressure between 22 and 36 mm Hg in at least
one eye, were randomly assigned in a 2:1 ratio to receive either Timolol GFS 0.5%
once daily or Timoptic XE 0.5% once daily, in a 12-month randomized, multicenter,
double-masked, prospective study. The primary efficacy variable was mean trough
intraocular pressure measured at 8:00 AM, approximately 24 hours after dosing.
RESULTS: The Timolol GFS 0.5% group produced significant trough intraocular
pressure reductions from a baseline of 4.5 to 5.2 mm Hg (P =.0001), compared with
reductions of 4.1 to 5. 3 mm Hg (P =.0001) in the Timoptic XE 0.5% group. The
difference in mean intraocular pressure between the two treatments was 0.9 mm Hg
or less, and the upper 95% confidence limit between groups was 0.92 mm Hg or less
at all time points, demonstrating both clinical and statistical equivalence. A
similar percentage of patients in the Timolol GFS 0.5% group (71%) and Timoptic
XE group (72%) had clinically relevant reductions in intraocular pressure. There
was no significant difference in the safety profiles of the two treatments.
CONCLUSION: Both treatments were clinically effective in lowering intraocular
pressure and maintaining the reductions over long-term use. Timolol GFS 0.5% is a
safe and effective therapy for open-angle glaucoma or ocular hypertension and is
both clinically and statistically equivalent to Timoptic XE 0.5% in reducing
intraocular pressure.
PMID- 11004288
TI - Effects of latanoprost and timolol-XE on hydrodynamics in the normal eye.
AB - PURPOSE: To compare the effects of latanoprost and timolol-XE on ocular pressure
and perfusion in healthy adults, with respect to episcleral venous pressure.
METHODS: A double-masked, placebo-controlled crossover study of weeklong bedtime
treatment with one drop of drug, with placebo contralaterally, followed by a 3
week washout and alternate-drug/contralateral-placebo repeat. Intraocular
pressure was measured by applanation and by pneumotonometry, providing pulsatile
ocular circulatory estimates. Measurements of episcleral venous pressure were
obtained (Friberg method). RESULTS: Twenty subjects participated (five men, 15
women; mean age, 39 years (range, 21 to 55 years); mean baseline intraocular
pressure, 13.4 mm Hg). A greater decrease in intraocular pressure was seen among
these subjects the morning after initiating treatment with latanoprost (-2.0 mm
Hg; P <.0001) than with timolol-XE (-0.9 mm Hg; P =.051) (latanoprost versus
timolol DeltaP =.008). This ocular hypotensive effect remained significant that
evening with latanoprost (-3.2 mm Hg; P <.0001) but not with timolol XE (-1.0 mm
Hg; P =.2). By the morning of day 8, mean intraocular pressure remained 3.2 mm Hg
below baseline with latanoprost and 2.3 mm Hg below baseline with timolol-XE (P
<.0001 for both drugs). Neither drug altered episcleral venous pressure. Among a
subgroup of nine subjects with comparable intraocular pressure reductions with
the two drugs, latanoprost treatment was associated with a 16.7% increase in mean
pulsatile ocular blood flow (P =.04) through the weeklong treatment interval,
consistently higher than during timolol-XE treatment of the same subjects.
CONCLUSION: Latanoprost caused an overnight decrease in intraocular pressure in
normotensive normal eyes, and both drugs significantly reduced intraocular
pressure within 1 week. Intraocular pressure remained higher than episcleral
venous pressure throughout treatment with both drugs. Latanoprost was associated
with enhanced pulsatile ocular perfusion not seen with timolol-XE treatment.
PMID- 11004289
TI - Learning effect, short-term fluctuation, and long-term fluctuation in frequency
doubling technique.
AB - PURPOSE: To evaluate short-term and long-term fluctuations and learning effects
in healthy subjects tested with the frequency doubling technique, which is based
on a low spatial frequency and a high temporal frequency stimulus. METHODS:
Twenty-three healthy adult subjects were consecutively recruited from volunteers,
and 20 subjects finished the study. All the visual fields were assessed by the
frequency doubling technique, program C-20, full threshold. The frequency
doubling technique presents stimuli on a black-and-white video monitor with
specialized control circuitry interfaced to a microprocessor. During program C
20, full threshold, 17 points are tested, one round point centrally and 16 square
ones in the periphery up to 20 degrees of eccentricity. Each stimulus consists of
a 0.25-cycle/degree sinusoidal grating undergoing a 25-Hz counterphase flicker.
One eye of each patient was chosen at random. Each subject was tested once in the
first session, three times in the second session, and once in the third and
fourth sessions. Both short-term and long-term fluctuation were studied either as
the average fluctuation value of all the points tested or as a point-to-point
fluctuation. To study the learning effect, the results of the first session were
compared with those of the second, the third, and the fourth sessions. RESULTS:
The average mean sensitivity of the three examinations of the second session was
30.4 +/- 1.24 dB, and the average short-term fluctuation of all the subjects was
2.16 +/- 0.5 dB. The short-term fluctuation of each point tested ranged from 1.4
to 3.4 dB. The average mean sensitivity for all the sessions was 32.4 +/- 1.14
dB, with an average long-term fluctuation of 3.23 +/- 0.5 dB, and the long-term
fluctuation of each tested point ranged from 2.5 to 4.4 dB. A mild learning
effect was found between the first section and the others. CONCLUSION: Short-term
and long-term fluctuations were similar to those known to occur with the
conventional threshold perimetry when they were compared with the literature
data. A learning effect was also observed and should be taken into account for
the clinical use of this test.
PMID- 11004290
TI - Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle
glaucoma.
AB - PURPOSE: To screen a population with primary open-angle glaucoma for mutations in
the gene that encodes the trabecular meshwork inducible glucocorticoid response
protein (TIGR), also known as myocilin (MYOC). METHODS: Ophthalmologic
information was collected for study subjects with primary open-angle glaucoma and
their relatives. Mutation screening of 74 primary open-angle glaucoma probands
was conducted by sequencing TIGR/MYOC coding sequence and splice sites. RESULTS:
In 23 families we detected 13 nonsynonymous sequence changes, nine of which
appear to be mutations likely to cause or contribute to primary open-angle
glaucoma. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence
variant, Asn57Asp, are novel. We found mutations in nine of 25 juvenile glaucoma
probands (36%) and two of 49 adult-onset glaucoma probands (4%). Age
classification of families rather than individual probands revealed mutations in
three of nine families with strictly juvenile primary open-angle glaucoma (33%),
and no mutations in 39 families with strictly adult-onset primary open-angle
glaucoma (0%). In families with mixed-onset primary open-angle glaucoma
containing both juvenile primary open-angle glaucoma and adult-onset primary open
angle glaucoma cases, we found mutations in eight of 26 families (31%).
CONCLUSIONS: Our data suggest that Gly252Arg, Arg272Gly, Glu323Lys, Gln368STOP,
Pro370Leu, Thr377Met, Val426Phe, Ile477Asn, and Ile499Ser are likely to play
roles that cause or contribute to the etiology of autosomal dominant primary open
angle glaucoma. Our finding of more TIGR/MYOC mutations in families with mixed
onset primary open-angle glaucoma than in the families with strictly adult-onset
primary open-angle glaucoma implies that the presence of relatives with juvenile
primary open-angle glaucoma in a family could be used as a basis for identifying
a subset of the population with adult-onset primary open-angle glaucoma with
higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine
estimations of mutation prevalence in these age-defined subpopulations,
prospective study of a larger population ascertained entirely through adult-onset
primary open-angle glaucoma probands will be needed.
PMID- 11004291
TI - Vitrectomy for diffuse diabetic macular edema associated with a taut premacular
posterior hyaloid.
AB - PURPOSE: To evaluate the role of vitrectomy in eyes with diffuse diabetic macular
edema associated with a taut posterior hyaloid. METHODS: Records of 55 eyes of 50
patients with diabetic retinopathy and diffuse clinically significant diabetic
macular edema who underwent vitrectomy with stripping of the premacular posterior
hyaloid were reviewed. In all 55 eyes, diffuse diabetic macular edema was present
on contact lens examination and confirmed with fluorescein angiography. On fundus
examination, the premacular posterior hyaloid was attached and appeared taut.
RESULTS: The mean preoperative best-corrected visual acuity was 20/160, and the
mean final best-corrected visual acuity was 20/80 (P <.0001, Wilcoxon signed rank
test), with 27 (49.1%) of the 55 eyes demonstrating improvement in best-corrected
visual acuity of 2 or more lines. Fifty-two (94.5%) of the 55 vitrectomized eyes
showed improvement in clinically significant macular edema and in 45 eyes (81.8%)
the macular edema resolved completely during a mean period of 4.5 months (range,
1 to 13 months). Eyes with macular ischemia and preoperative best-corrected
visual acuity of 20/200 or less tended to respond less favorably to vitrectomy
than eyes lacking these characteristics. All eyes had at least 6 months of follow
up after surgery, with a mean follow-up of 23.2 months. CONCLUSION: In eyes with
persistent diffuse diabetic macular edema with a taut premacular posterior
hyaloid face unresponsive to laser therapy, vitrectomy with removal of the
posterior hyaloid appears to be beneficial in some cases. Careful selection of
eyes with favorable preoperative clinical characteristics may improve surgical
outcomes.
PMID- 11004292
TI - Submacular surgery to remove choroidal neovascularization associated with central
serous chorioretinopathy.
AB - PURPOSE: To report the results of submacular surgery for removal of choroidal
neovascularization associated with central serous chorioretinopathy. METHODS: Ten
eyes of nine consecutive patients with central serous chorioretinopathy and
subfoveal or juxtafoveal choroidal neovascularization underwent pars plana
vitrectomy with removal of the choroidal neovascular membrane between January
1994 and January 1999. RESULTS: All 10 eyes (nine patients) were followed
postoperatively for at least 6 months. The mean postoperative follow-up was 23
months (range, 6 to 56.5 months). The patients were followed for an average of
6.2 months from the time of symptoms to the removal of the choroidal
neovascularization. Preoperative mean best-corrected visual acuity was 20/100
(range, 20/25 to 20/400), and postoperative best-corrected mean visual acuity was
20/60 + 2 (range, 20/20 to 20/400). Seven eyes had improved postoperative visual
acuity, with an average of 3.4 lines gained. Of the three eyes that had worse
acuity, an average of 1.3 lines of visual acuity was lost; final mean
postoperative visual acuity was 20/80 + 1 (range, 20/25 to 20/400). Of the six
eyes with symptoms of less than 3 months' duration, four had a final visual
acuity of 20/50 or better. All three eyes with 20/300 or worse final visual
acuity had loss of foveal retinal pigment epithelium after surgery; the remaining
eyes had preserved retinal pigment epithelium with a visual acuity of 20/70 or
better. Two eyes had intraoperative peripheral retinal tears, and two eyes had
recurrence of the choroidal neovascular complex. CONCLUSIONS: The anatomic and
visual results in eyes with choroidal neovascularization associated with central
serous chorioretinopathy are modestly encouraging and suggest that submacular
surgery for choroidal neovascularization in patients with central serous
chorioretinopathy is a treatment option that may salvage good macular function in
some eyes.
PMID- 11004293
TI - Tomographic features of early macular hole closure after vitreous surgery.
AB - PURPOSE: To report the optical coherence tomographic features of macular hole
closure in the first months after vitreous surgery. METHODS: We studied
prospectively the tomographic features of 28 eyes (28 patients) with idiopathic
macular holes before and after vitreous surgery by optical coherence tomography.
We compared the best-corrected visual acuity levels with the postoperative
tomographic features. RESULTS: The 25 eyes with successfully sealed macular holes
had one of two tomographic features within 1 month postoperatively: simple
closure (normal foveal configuration) in 14 eyes (56%) or a bridge formation at
the fovea that mimicked a foveal retinal detachment in 11 eyes (44%). It took an
average of 2.0 months (range, 0.8 to 3.5 months) for the bridge tissue to attach
to the retinal pigment epithelium. Best-corrected visual acuity quickly improved
in the former group; visual improvement began 1 month after attachment of the
bridge tissue in the latter group. A closed hole reopened 4 months
postoperatively in one eye with a bridge formation. CONCLUSIONS: Idiopathic
macular holes have one of two patterns early after surgical closure, simple
closure or a bridge formation. Visual improvement starts after the fovea assumes
a normal configuration. The bridge formation appears to reflect an early phase
and fragile condition in the anatomic closure of macular holes.
PMID- 11004294
TI - A new locus for dominant drusen and macular degeneration maps to chromosome 6q14.
AB - PURPOSE: To report the localization of a gene causing drusen and macular
degeneration in a previously undescribed North American family. METHODS: Genetic
mapping studies were performed using linkage analysis in a single family with
drusen and atrophic macular degeneration. RESULTS: The clinical manifestations in
this family ranged from fine macular drusen in asymptomatic middle-aged
individuals to atrophic macular lesions in two children and two elderly patients.
We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644.
CONCLUSIONS: In a family with autosomal dominant drusen and atrophic macular
degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus
appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7
(CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of
the gene responsible for the disease in this family will provide a better
understanding of macular degeneration.
PMID- 11004295
TI - Clinical spectrum of chromosome 6-linked autosomal dominant drusen and macular
degeneration.
AB - PURPOSE: To describe the clinical phenotype and the intrafamilial variation in
retinal findings in a North American family with an autosomal dominant drusen
disorder that maps to chromosome 6q14. METHODS: Ophthalmic examinations were
carried out on participating family members. Fundus photographs were obtained
whenever possible. Electroretinography was performed on the proband and her
father. Blood was drawn for DNA analysis. RESULTS: Twelve family members had
drusen and/or atrophic macular degeneration. The disease in asymptomatic young
adults is characterized by fine drusen that are most conspicuous in the macula.
The proband presented at 3 years of age with atrophic maculopathy and drusen. Her
cousin was found to have atrophic macular lesions and drusen in the first year of
life. Two older affected individuals have reduced vision from cicatricial and
atrophic macular changes. The gene for the disease was mapped to chromosome 6q14
and appears to be adjacent to but distinct from the locus for North Carolina
macular dystrophy. CONCLUSIONS: There is extreme variability in the clinical
expression of this dominant form of drusen and macular degeneration. Most young
adults have fine macular drusen and good vision. Affected infants and children
may have congenital atrophic maculopathy and drusen. There is historical evidence
of progression of the disease in late adulthood with moderate visual loss.
PMID- 11004296
TI - Lymphocytic choriomeningitis virus: an underdiagnosed cause of congenital
chorioretinitis.
AB - PURPOSE: To elucidate the role and clinical spectrum of congenital lymphocytic
choriomeningitis virus infection as a cause of chorioretinopathy, congenital
hydrocephalus, and macrocephaly or microcephaly in the United States. METHODS: We
performed complete ophthalmologic surveys of all residents at Misericordia, a
home for the severely mentally retarded in Chicago, and prospectively evaluated
all patients with chorioretinitis or chorioretinal scars during a 36-month period
at Children's Memorial Hospital, also located in Chicago. Sera for patients
demonstrating chorioretinal scars (a sign of intrauterine infection) were tested
for Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus
and lymphocytic choriomeningitis virus antibodies. RESULTS: Four of 95 patients
examined at the home had chorioretinal scars, and two of these patients had
normal T. gondii, rubella virus, cytomegalovirus, and herpes simplex virus titers
and dramatically elevated titers for lymphocytic choriomeningitis virus. Three of
14 cases of chorioretinitis at the hospital had normal T. gondii, rubella virus,
cytomegalovirus, and herpes sim-plex virus titers and elevated lymphocytic
choriomeningitis virus antibody titers. (A fourth case, diagnosed in 1996, was
reported 2 years ago.) CONCLUSIONS: Lymphocytic choriomeningitis virus was
responsible for visual loss in two of four children secondary to chorioretinitis
in a population of severely retarded children. The six new cases of lymphocytic
choriomeningitis virus chorioretinitis identified in these two populations over
the last 3 years, compared with the total number ever reported in the United
States (10 cases), suggests that lymphocytic choriomeningitis virus may be a more
common cause of congenital chorioretinitis than previously believed. Because its
consequences for visual and psychomotor development are devastating, we conclude
that the workup for congenital chorioretinitis should include lymphocytic
choriomeningitis virus serology, especially if T. gondii, rubella virus,
cytomegalovirus, and herpes simplex virus titers are negative.
PMID- 11004297
TI - Isolated comitant esotropia and Chiari I malformation.
AB - PURPOSE: To report four patients with isolated comitant esotropia and Chiari I
malformation and discuss the most appropriate management. METHODS: Case reports
and literature review. RESULTS: All four patients (5, 14, 16, and 37 years of
age) presented with an isolated comitant esotropia that led to the diagnosis of
Chiari I malformation. The first two patients underwent uncomplicated
neurosurgical decompression of their malformation, followed by complete
resolution of their esotropia. The third patient underwent strabismus surgery and
experienced initial resolution of the esotropia, but eventual recurrence resulted
in the strabismus surgery being repeated 5 years later. The fourth patient had
strabismus surgery with resolution of the esotropia but only 2 months of follow
up. CONCLUSION: Although management of patients with Chiari I malformation and
severe neurologic findings typically includes surgical decompression, management
is less straightforward in cases with subtle findings or in which ocular findings
are isolated. The decision to perform neurosurgical decompression or strabismus
surgery should still be made on a case-by-case basis, with the understanding that
strabismus surgery may provide only temporary ocular alignment.
PMID- 11004298
TI - Monitoring patients taking oral carbonic anhydrase inhibitors.
AB - Although no prospective studies have been done and no recommendations can be
reasonably evidenced based, we believe that our "alternative views" are reason
able, taking into account the serious nature of aplastic anemia and its more
favorable prognosis when this disorder is treated early. Because aplastic anemia
represents only about one half of possible CAl blood dyscrasias, early
recognition of non-aplastic anemia dyscrasias alone Justifies hematologic
screening.
PMID- 11004299
TI - International Federation of Ophthalmological Societies statutes and regulations.
AB - PURPOSE: To provide an understanding of the structure, role, and responsibility
of the International Federation of Ophthalmological Societies, the International
Council of Ophthalmology, and the International Congress of Ophthalmology. These
established entities have recently codified their statutes and regulations and
registered them in Zurich, Switzerland. METHODS: The International Council of
Ophthalmology, which serves as the executive body of the International Federation
of Ophthalmological Societies, used historical operating documents to prepare the
statutes and regulations, which were reviewed and adopted by the International
Federation of Ophthalmological Societies at the 28th International Congress of
Ophthalmology in Amsterdam on June 23, 1998. RESULTS: The statutes and
regulations of the International Federation of Ophthalmological Societies, the
International Council of Ophthalmology, and the International Congress of
Ophthalmology are available to supranational ophthalmological organizations,
national ophthalmological societies, other ophthalmological organizations, and
individual ophthalmologists. CONCLUSIONS: The statutes and regulations of the
International Federation of Ophthalmological Societies, the International Council
of Ophthalmology, and the International Congress of Ophthalmology provide a basis
for an organizational structure in international ophthalmology. The International
Congress of Ophthalmology, first held in 1857, is the longest continuing
international meeting in medicine. The International Council of Ophthalmology was
established in 1927, and the International Federation of Ophthalmological
Societies was formed in 1933. These organizations coordinate the International
Congress of Ophthalmology, which convenes with the International Federation of
Ophthalmological Societies every 4 years. The International Council, as the
executive body, meets annually. The International Council of Ophthalmology has
for decades worked to coordinate and facilitate interchange, education, and
standards in international ophthalmology. Currently, the International Council of
Ophthalmology, working with other international organizations, is creating an
international ophthalmology strategic plan, which includes focus on ophthalmic
training, continuing education, advocacy for the preservation and restoration of
vision, clinical guidelines, and research.
PMID- 11004300
TI - Blepharoptosis-induced superior keratoconus.
AB - PURPOSE: This clinical case report demonstrates blepharoptosis-induced corneal
steepening and its subsequent resolution after blepharoptosis surgery. METHODS: A
62-year-old man complaining of blurred vision without apparent cause on clinical
examination underwent keratometry and computerized corneal topography, which
revealed superior corneal steepening in both eyes. Bilateral upper eyelid
blepharoptosis surgery was performed. RESULTS: Three months after blepharoptosis
surgery, repeat computerized corneal topography revealed normal corneal contours
with improved vision in both eyes. CONCLUSIONS: Blepharoptosis is a common
condition that may induce superior corneal ectasia that is not evident by
manifest refraction, slit-lamp examination, or keratometry. Computerized corneal
topography can help detect such subtle corneal abnormalities and guide therapy.
PMID- 11004301
TI - Air bag-induced corneal flap folds after laser in situ keratomileusis.
AB - PURPOSE: We describe a case of air bag-induced ocular trauma resulting in folds
in the corneal flap 3 weeks after laser in situ keratomileusis. METHODS: Case
report. Three weeks after laser in situ keratomileusis, a 20-year-old man was
involved in a motor vehicle accident and sustained blunt trauma to the right eye,
which caused corneal flap folds, corneal edema, anterior chamber cellular
reaction, and Berlin retinal edema. RESULTS: Six weeks after laser in situ
keratomileusis, persistent flap folds necessitated re-operation with lifting of
the flap and repositioning. One week after the procedure, the visual acuity
improved to 20/20-2, and the folds had cleared. CONCLUSION: Trauma after laser in
situ keratomileusis may produce folds in the corneal flap. With persistence of
these folds, management by lifting and repositioning the corneal flap may be
necessary to permit recovery of visual acuity.
PMID- 11004302
TI - Compound nevus of the cornea simulating a foreign body.
AB - PURPOSE: To report a corneal nevus, without conjunctival involvement, that
clinically simulated a metallic foreign body. METHODS: Case report with
clinicopathologic correlation. RESULTS: A 22-year-old man developed a superficial
pigmented lesion of his left cornea. It was suspected to be a chronically
retained foreign body, but a melanocytic neoplasm could not be excluded. The
lesion was removed by lamellar keratectomy and proved histopathologically to be a
compound nevus of the cornea, without conjunctival involvement. CONCLUSIONS:
Melanocytic nevus can rarely occur in the cornea. Involvement of the cornea by a
melanocytic lesion does not necessarily imply a malignant melanoma.
PMID- 11004303
TI - Iris color and cataract: the Blue Mountains Eye Study.
AB - PURPOSE: To investigate the relationship between eye color and cataract. METHODS:
A population-based cross-sectional study (N = 3654) was conducted near Sydney,
Australia. Lens photographs were graded for cortical, nuclear, and posterior
subcapsular cataract. Iris color was assessed at slit-lamp examination by
comparison with four photographic standards. RESULTS: Eyes with dark brown irises
were more likely to have nuclear (adjusted odds ratio, 1.59; 95% confidence
interval [CI], 1.03 to 2.28) or posterior subcapsular cataract (adjusted odds
ratio, 2.50; 95% CI, 1.57 to 3.98) than eyes with lighter-colored irises.
CONCLUSIONS: People with dark brown eyes are at increased risk of cataract and
should be encouraged to protect their eyes from direct exposure to sunlight.
PMID- 11004304
TI - Tonic pupil associated with congenital neuroblastoma, Hirschsprung disease, and
central hypoventilation syndrome.
AB - PURPOSE: To report the association of tonic pupil, congenital neuroblastoma,
Hirschsprung disease, and central hypoventilation syndrome. METHODS: Case
reports. RESULTS: Two infants with central hypoventilation syndrome and
Hirschsprung disease were evaluated for dilated, nonreactive pupils present since
birth. In both cases, pharmacologic testing with dilute pilocarpine confirmed
denervation supersensitivity consistent with tonic pupil. The diagnosis of
congenital neuroblastoma was subsequently established in both infants.
CONCLUSIONS: The close association of these conditions in these two young
children supports the concept of a common neural crest abnormality being present.
A careful systemic evaluation to rule out congenital neuroblastoma should be
performed in any young child who presents with tonic pupil in the setting of
central hypoventilation syndrome and Hirschsprung disease.
PMID- 11004305
TI - Systemic toxicity of topical and periocular corticosteroid therapy in an 11-year
old male with posterior uveitis.
AB - PURPOSE: To report a case of systemic corticosteroid toxicity resulting from
topical and periocular therapy. METHODS: Treatment and follow-up of an 11-year
old male with uveitis are illustrated. Initial presentation of the patient was
bilateral iridocyclitis, for which he was treated with prednisolone acetate 1%
every 2 hours for 6 months. Subsequently, posterior uveitis developed,
necessitating posterior subtenon injections. RESULTS: After initial topical
corticosteroid therapy, the patient developed a cushingoid habitus accompanied by
increased lanugo hair, acanthosis nigricans, posterior subcapsular lens
opacities, and increased intraocular pressure. Cushingoid stigmata worsened after
administration of posterior subtenon injection of corticosteroids. The patient's
truncal obesity worsened, and his linear growth stopped. CONCLUSIONS: Systemic
toxic effects may develop as a result of topical and local use of ophthalmic
corticosteroid preparations in susceptible patients.
PMID- 11004306
TI - Reversible bull's-eye maculopathy associated with intravitreal fomivirsen therapy
for cytomegalovirus retinitis.
AB - PURPOSE: To report two cases in which a bull's eye maculopathy developed after
intravitreal injection of fomivirsen. METHODS: Case reports. RESULTS: A 50-year
old man with acquired immunodeficiency syndrome (AIDS) and refractory
cytomegalovirus retinitis developed bull's-eye pigmentary changes in the macula
of the right eye after initiating therapy with fomivirsen (Vitravene; CIBA
Vision, Atlanta, Georgia) intravitreal injections. These pigmentary changes
resolved upon cessation of treatment. A 36-year-old man with AIDS and refractory
bilateral cytomegalovirus retinitis developed bull's-eye pigmentary changes in
both eyes during bilateral intravitreal treatment with fomivirsen. Vision was not
affected. These changes resolved after treatment with fomivirsen was stopped.
CONCLUSION: Fomivirsen, a new medication for the treatment of refractory
cytomegalovirus retinitis, may cause a bull's-eye maculopathy in some patients.
The bull's-eye maculopathy is reversible and does not appear to affect vision.
PMID- 11004307
TI - Clonally accumulating T cells in the anterior chamber of Behcet disease.
AB - PURPOSE: To clarify the nature of infiltrating T cells into the anterior chamber
of a patient with Behcet disease. METHODS: Aqueous humor was obtained from a
patient with ocular Behcet disease by paracentesis. RNA isolated from the cells
in aqueous humor was reverse transcribed into complementary DNA. Complementary
DNA encoding the variable (V) diversity (D) joining (J) (junctional) region of T
cell receptor beta chain V domain (TCR BV) chain was amplified by T-cell receptor
BV family polymerase chain reaction. RESULTS: Polymerase chain reaction Southern
blot analysis showed that T-cell receptor BV3, BV5, and BV7 were dominantly
expressed on ocular T cells of this patient. In addition, DNA sequencing revealed
that monoclonal or oligoclonal T-cell accumulation was found in T-cell receptor
BV3(+), BV5(+), and BV7(+) T cells. CONCLUSION: These findings suggest that some
T cells infiltrating into the anterior chamber of a patient with ocular Behcet
disease expand by antigen-driven stimulation, indicating the pivotal role of T
cells in the pathogenesis of ocular Behcet disease.
PMID- 11004309
TI - Choroidal neovascularization with granulomatous inflammation in ocular
histoplasmosis syndrome.
AB - PURPOSE: To report pathologic examination of an excised choroidal neovascular
membrane in a patient with ocular histoplasmosis syndrome that demonstrated
granulomatous inflammation. METHOD: Case report. A 50-year-old woman with sudden
vision loss in her left eye demonstrated clinical and fluorescein angiographic
findings characteristic of choroidal neovascularization secondary to ocular
histoplasmosis syndrome. RESULTS: Histopathologic examination of the surgically
excised choroidal neovascular membrane disclosed granulomatous inflammation.
CONCLUSIONS: This case suggests an important role of mononuclear phagocytic cells
as primary mediators of angiogenesis or modifiers of choroidal
neovascularization. This association of choroidal neovascularization with
granulomatous inflammation did not respond to treatment with systemic
corticosteroids.
PMID- 11004308
TI - Lymphocytic choriomeningitis virus chorioretinitis mimicking ocular toxoplasmosis
in two otherwise normal children.
AB - PURPOSE: To report unilateral macular lesions, mimicking toxoplasmic scars, in
two children with serological evidence for lymphocytic choriomeningitis virus
infection. METHODS: Case reports. RESULTS: Patients were 4 and 5 years old, with
negative toxoplasma serologies and no sign of rubella, cytomegalovirus, or herpes
simplex infection (TORCH evaluation). Lymphocytic choriomeningitis virus
infection was detected in both cases by enzyme-linked immunosorbent assay and
confirmed by Western immunoblotting. The modes of infection were unknown; no
history of symptomatic systemic lymphocytic choriomeningitis virus infection was
reported, and lymphocytic choriomeningitis virus serologies were negative in the
mothers of the patients. Neurological examinations and brain magnetic resonance
imaging were normal. CONCLUSION: Our observations suggest that chorioretinal
scars can be an isolated manifestation of lymphocytic choriomeningitis virus
infection.
PMID- 11004310
TI - Chorioretinal involvement in primary systemic nonfamilial amyloidosis.
AB - PURPOSE: To report a case of primary systemic nonfamilial amyloidosis studied by
fluorescein angiography and indocyanine green angiography. METHODS: Case report.
A 59-year-old woman with primary systemic nonfamilial amyloidosis presented
bilateral diffuse deep hemorrhages and pigmentary mottling at the posterior pole.
RESULTS: On fluorescein angiography bilateral diffuse areas of hypofluorescence
were present. Indocyanine green angiography showed large hypofluorescent areas
with hypofluorescent lines in the midperiphery and hyperfluorescent streaks in
the peripapillary area. CONCLUSIONS: In this case of primary systemic nonfamilial
amyloidosis, diffuse bilateral chorioretinal abnormalities included hemorrhages
and pigmentary mottling at the posterior pole, with hypofluorescent areas on
fluorescein angiography and indocyanine green angiography, as well as
hypofluorescent lines in the midperiphery.
PMID- 11004311
TI - Traumatic displacement of the globe into the ethmoid sinus.
AB - PURPOSE: To describe displacement of the globe into the ethmoid sinus after an
orbital trauma. METHOD: Case report. A 58-year-old man sustained trauma of the
left eye and orbit, which resulted in displacement of the globe into the ethmoid
sinus. One day after injury, surgery was performed to restore the intact globe
into position within the orbit. RESULTS: After operation, the globe held in its
anatomical site, and 10 months after surgery the visual acuity was 20/100, slight
pallor of the optic disk was present, and there was no limitation of the
horizontal and vertical ductions. CONCLUSIONS: To our knowledge, this is the
first case of traumatic displacement of the globe into the ethmoid sinus with
satisfactory restoration of normal globe position and preservation of vision.
PMID- 11004312
TI - Bilateral papilledema from a massive intracranial epidermoid cyst.
AB - PURPOSE: To report an unusual case of bilateral papilledema from a large
intracranial epidermoid cyst. METHODS: Case report. RESULTS: A 26-year-old man
presented with visual loss, bilateral papilledema, and only a few neurological
symptoms. Magnetic resonance imaging disclosed such a large lesion that his right
cerebral hemisphere was compressed to one half its normal size. Histopathologic
examination of the completely removed tumor revealed an epidermoid cyst.
CONCLUSION: This unique case involved a patient with bilateral papilledema caused
by a huge intracranial epidermoid cyst. Epidermoid tumors should be considered in
the differential diagnosis of papilledema.
PMID- 11004314
TI - Hallucinations in Parkinson's disease. prevalence, phenomenology and risk
factors. Fenelon G* mahieux F, huon R, Ziegler M. Brain 2000;123:733-745
PMID- 11004313
TI - Physicians and the pharmaceutical industry: is a gift ever just a gift? wazana
A.* JAMA 2000;283:373-380
PMID- 11004316
TI - Recovery from optic neuritis is associated with a change in the distribution of
cerebral response to visual stimulation: a functional magnetic resonance imaging
study. Werring DJ, bullmore ET, toosy AT, miller DH, barker GJ, MacManus DG,
brammer MJ, giampietro VP, brusa A, brex PA, moseley IF, plant GT, McDonald WI,
thompson AJ. * J neurol neurosurg psychiatry 2000;68:441-449
PMID- 11004315
TI - Visual loss after spine surgery: a survey. Cheng MA, sigurdson W, tempelhoff R,
lauryssen C.* neurosurgery 2000;46:625-631
PMID- 11004318
TI - Is CS gas dangerous? fraunfelder FT.* Br med J 2000; 320:458-459
PMID- 11004317
TI - Foveal relocation by redistribution of the neurosensory retina. Wong D* lois N.
Br J ophthalmol 2000;84:352-357
PMID- 11004320
TI - Supplemental perioperative oxygen to reduce the incidence of surgical-wound
infection. Grief R, Akca O, horn E-P, kurz A, sessler DI* for the outcomes
research group. N engl J med 2000;342:161-167
PMID- 11004319
TI - Black diaphragm aniridia intraocular lens for congenital aniridia: long-term
follow-up. Reinhard T* engelhardt S, sundmacher R. J cataract refract surg
2000;26:375-381
PMID- 11004322
TI - A prospective search for ocular lesions in hospitalized patients with significant
bacteremia. Bouza E* cobo-soriano R, Rodriquez-Creixems M, Munoz P, Suarez-leoz
M, Cortes C. Clin infect dis 2000;30:306-312
PMID- 11004321
TI - The elusive causes of keratoconus: a working hypothesis. Kenny MC* brown DJ,
rajeev B. CLAO J. 2000;26: 10-13
PMID- 11004323
TI - Risk factors for cortical, nuclear, and posterior subcapsular cataracts: the POLA
study. Delcourt C* cristol J-P, tessier F, Leger CL, michel F, papoz L, and the
POLA study group. Am J epidemiol 2000;151:497-504
PMID- 11004324
TI - Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro
model of conjunctival cells. De saint jean M, debbasch C, brignole F, rat P,
warnet J-M, baudouin C.* curr eye res 2000;20:85-94
PMID- 11004325
TI - Faith, hope, and ant piles.
PMID- 11004326
TI - Intermittent and continuous ceftazidime infusion for critically ill trauma
patients.
AB - BACKGROUND: The adequacy of intermittent and continuous infusion ceftazidime for
the treatment of nosocomial pneumonia in critically ill trauma patients was
assessed by analyzing ceftazidime pharmacokinetics in relation to the minimum
inhibitory concentration (MIC) and treatment outcome. METHODS: Serial blood
samples were obtained during ceftazidime therapy in 31 trauma patients.
Ceftazidime pharmacokinetics were compared with that of previously studied
healthy volunteers. Ceftazidime pharmacokinetics were analyzed according to the
time above the MIC and treatment outcome. RESULTS: Critically ill trauma patients
had a significantly increased volume of distribution and clearance (0.32 +/- 0.14
L/kg and 2.35 +/- 0.89 mL. min(-1). kg(-1), respectively) compared with healthy
volunteers (0.21 +/- 0.03 and 1.58 +/- 0.23 mL. min(-1). kg(-1)). The time above
the MIC was >/=92% of the dosing interval for all patients and treatment outcomes
were similar between the two treatment groups. CONCLUSIONS: Ceftazidime
pharmacokinetics are significantly altered in critically ill trauma patients.
Both intermittent and continuous ceftazidime regimens were equally effective for
the treatment of nosocomial pneumonia caused by less virulent bacteria.
PMID- 11004327
TI - Cost analysis of breast conservation surgery compared with modified radical
mastectomy with and without reconstruction.
AB - BACKGROUND: Breast conservation surgery (BCS), consisting of lumpectomy, axillary
lymph node dissection, and radiation therapy, is as effective as modified radical
mastectomy (MRM) for the treatment of early stage breast cancer. The costs of
these treatment options have not been adequately addressed in the current era of
increasing utilization of BCS and breast reconstruction. The purpose of this
study is to determine differences in treatment costs among BCS, MRM alone, and
MRM with reconstruction. METHODS: Patients with stage I and II breast cancer
receiving inpatient treatment at a private university-affiliated hospital between
January 1996 and July 1997 were analyzed (n = 230). Charges were determined as
follows: inpatient and radiotherapy charges from the hospital billing department,
surgeon fees from group practice billing codes, and radiotherapy physician fees
from the radiation oncology group practice. Inpatient length of stay was obtained
from hospital medical records. RESULTS: Average hospital inpatient charge for BCS
was $4,748 (n = 74), $6,280 for MRM alone (P <0.001, n = 132), and $11,946 for
MRM with reconstruction (P <0.001, n = 24). Surgeons' fees for BCS were $2,840,
$3,500 for MRM alone, and $10,774 for MRM with reconstruction. The average
radiotherapy charge was $18,742. Average length of stay was 1.03 days for BCS,
2.44 days for MRM alone (P <0.001), and 3.71 days for MRM with reconstruction (P
<0. 001). Average total cost of BCS ($26,330) was significantly greater than the
average total cost of either MRM alone ($9,780, P <0.001) or MRM with
reconstruction ($22,720, P <0.001). CONCLUSIONS: BCS is more expensive than MRM
with or without reconstruction. It is the addition of radiotherapy that results
in the higher total cost of CS.
PMID- 11004328
TI - The correlation of axillary ultrasonography with histologic breast cancer
downstaging after induction chemotherapy.
AB - BACKGROUND: The goal of this study was to examine the role of ultrasonography in
detecting axillary lymph node metastases in stage II breast cancer patients after
induction chemotherapy (IC). METHODS: Of 172 consecutive patients with T1-3, N0
1, M0 breast cancer registered in a prospective IC trial, a subset of 130
evaluable patients were chosen, with (1) both physical and ultrasonographic
examinations of the axilla before and after IC; (2) exactly four cycles of IC;
(3) no presurgical radiation therapy; and (4) an axillary lymph node dissection.
RESULTS: Before IC, 32 patients (25%) were negative for axillary involvement by
both physical and ultrasonographic examinations. After IC, this number increased
to 64 (49%). Of these, 31 (48%) were positive by pathology examination. In most
cases, however, the residual tumor was minimal. CONCLUSIONS: Stage II breast
cancer patients who were or became node negative by both ultrasonographic and
physical examinations after IC had a 48% incidence of nodal metastases. Because
the residual tumor was minimal, irradiation may be sufficient for adequate local
control of the axilla.
PMID- 11004329
TI - Defining a role for endoscopic ultrasound in staging periampullary tumors.
AB - BACKGROUND: The goal of the preoperative workup in patients with suspected
periampullary carcinoma is to establish the diagnosis with a high degree of
certainty. In this study we compared endoscopic ultrasonography (EUS) and
computed tomography (CT) scans for the detection of tumor, lymph node metastasis,
and vascular invasion in patients with suspected periampullary carcinoma in order
to define a role for EUS in the preoperative staging of these patients. METHODS:
Thirty-seven consecutive patients received EUS and CT scanning followed by
operation for presumed periampullary carcinoma during a 30-month period. Both
imaging modalities were reviewed in a blinded fashion and the results compared
with pathology and operative reports on all patients. RESULTS: Sensitivity,
specificity, positive predictive value, and negative predictive value for tumor
detection by EUS were 97%, 33%, 94%, and 50%, respectively, compared with 82%,
66%, 97%, and 25% for CT scan. For lymph nodes the values were 21%, 80%, 57%, and
44%, respectively, for EUS compared with 42%, 73%, 67%, and 50% for CT. For
vascular invasion, the values were 20%, 100%, 100%, and 89%, respectively, for
EUS, compared with 80%, 87%, 44%, and 96% for CT. CONCLUSIONS: CT is the initial
study of choice in patients with suspected periampullary tumors. EUS is superior
for detecting tumor and for predicting vascular invasion. Therefore, EUS should
be used for patients in whom CT does not detect a mass and for those with an
identifiable mass on CT in whom vascular invasion cannot be ruled out.
PMID- 11004330
TI - Utility of fluorine-18-fluorodeoxyglucose positron emission tomography in
differentiated thyroid carcinoma with negative radioiodine scans and elevated
serum thyroglobulin levels.
AB - BACKGROUND: This study aimed to determine the role of fluorine-18
fluorodeoxyglucose positron emission tomography (FDG-PET) in the follow-up of
patients who underwent total thyroidectomy and iodine-131 ((131)I) ablation
therapy for differentiated thyroid cancer and presented increased thyroglobulin
levels with negative (131)I and thallium-201 ((201)Tl) scans. METHODS: Two
patients with follicular carcinoma and eight with papillary tumors underwent
total thyroidectomy and (131)I therapy until the (131)I scan was negative. (131)I
and (201)Tl scans were performed with negative results in all cases, while serum
thyroglobulin measurements were all positive with negative thyroglobulin
autoantibodies. One week after the (131)I scans, all the patients underwent FDG
PET whole-body scans. RESULTS: The FDG-PET scan detected in 4 patients, a single
focal increase of FDG uptake in one lymph node metastasis (subsequently confirmed
histologically); in 1 patient, multiple pathological focal uptakes in brain,
neck, and chest; and in 1 patient, two mild focal uptakes in the mediastinum,
close to the tracheal branch. In 2 other patients, pathological FDG uptakes in
cervical spine and mediastinum were not confirmed by other imaging techniques,
and in the 2 remaining patients the scan results were inconclusive. The
sensitivity of FDG-PET whole-body scan for detecting metastatic thyroid cancer
was 60%. CONCLUSIONS: This study indicates that the FDG-PET whole-body scan is a
useful tool in the follow-up of patients with differentiated thyroid cancer,
negative (131)I and (201)Tl scans and elevated serum thyroglobulin levels. The
FDG-PET scan detects metastatic disease in 60% of patients with differentiated
thyroid cancer, enabling surgical therapy to be performed on accessible lesions.
PMID- 11004331
TI - Physician leadership is essential to the survival of teaching hospitals.
AB - BACKGROUND: Academic medical centers (AMCs) face severe financial constraints
because they must now compete directly with private providers that focus
exclusively on cost-effective healthcare delivery. Educational and research
capacities developed at AMCs have been supported by government and third party
payers, but government support is diminishing. Physicians are ill-equipped to
respond to market pressures. DATA SOURCES: Analyses of cultural change and
restructuring in corporate giants such as Greyhound, IBM and FedEx are relevant
to teaching hospitals. To succeed, organizations must flatten hierarchy, empower
staff, train leaders, and mobilize intellectual capital. Effective leadership is
essential. CONCLUSION: Physicians must educate themselves on forces impacting the
AMC, understand changes needed in the structure and processes of AMC governance
and acquire competencies for leadership and management if AMCs are to survive and
thrive. Surgeons should acquire competencies that will enable them to become
leaders in the process of AMC transformation.
PMID- 11004332
TI - Visual-spatial abilities in surgical training.
AB - As surgery continues to advance, we will need to better understand the role
visual-spatial abilities play in the acquisition of technical skills. Many
universities have established surgical skills centers with specific curricula to
teach residents technical skills as adjuncts to operating room learning. Yet, as
educators we do not fully understand the role visual-spatial abilities plays in
the acquisition of surgical skills. This paper summarizes the research to date on
the relevance of visual-spatial abilities to surgical training.
PMID- 11004333
TI - Availability of content information does not improve performance on computerized
case simulations.
AB - BACKGROUND: A previous study evaluated repeated, serial administrations of
computer-based simulations. The data demonstrated an increase in scores across
rotations during the academic year, but no difference between scores in
successive years. METHODS: The initial study only indirectly assessed the effect
of information sharing on measured performance. To directly assess the effect of
information transfer, 8 computer-based case simulations were administered over 2
consecutive years to 220 third-year students at the conclusion of 12 surgical
clerkship rotations (6 per year). During the second year of administration
information regarding content area, in the form of the case stem or introductory
lead-in material, was provided to each rotation of students prior to the
examination based on a sequential algorithm. RESULTS: The data demonstrate no
increase in overall mean score for the examination over the 2 years. Scores were
significantly different for 2 of the 8 cases, increasing in the one and
decreasing in the other. CONCLUSIONS: The data demonstrate no evidence that prior
knowledge of content area influences the scores of successive classes on
computerized models of performance assessment.
PMID- 11004334
TI - Initial results with a stapled gastrojejunostomy for the laparoscopic isolated
roux-en-Y gastric bypass.
AB - BACKGROUND: The gastric pouch to jejunum anastomosis is a critical step in the
performance of an isolated Roux-en-Y gastric bypass. When performing this
procedure laparoscopically, intracorporeal suturing of the gastric pouch to Roux
en-Y jejunum anastomosis is technically demanding, time consuming, and perhaps
the most prohibitive part of the operation. We devised a unique, effective, and
simple method to perform this anastomosis using an EEA stapler. This report
describes this technique and its follow-up in our series of patients undergoing a
laparoscopic isolated Roux-en-Y gastric bypass utilizing this technique. METHODS:
A prospective analysis was performed identifying the technical success, leak
rate, and postoperative incidence of anastomotic stenosis and its management in a
consecutive series of patients undergoing a laparoscopic isolated Roux-en-Y
gastric bypass with a gastrojejunal anastomosis constructed with a 21-mm or 25-mm
EEA stapler. RESULTS: Forty-eight patients underwent laparoscopic isolated Roux
en-Y gastric bypass. Mean age was 40.9 years (range 22 to 64) and mean body mass
index was 52.3 kg/m(2) (range 31 to 76 kg/m(2)). There were no mortalities. Three
patients (6.3%) were converted to an open procedure, but only 1 because of an
inability to perform the gastrojejunal anastomosis (short jejunal mesentery).
There was 1 leak (2.1%) from the gastrojejunal anastomosis. It was successfully
managed nonoperatively. Thirteen patients (27.1%) patients developed an
anastomotic stenosis requiring endoscopic balloon dilatation. Seven of the 13
patients required only a single dilatation and have had no recurrence of
dysphagia. Six of the 13 patients needed 2 to 4 dilatations, and all are
swallowing normally. None have required surgical revision. After 12 months of
follow-up, the mean weight loss was 115 pounds and mean decrease in body mass
index was 18.5 kg/m(2). CONCLUSIONS: The stapled EEA gastrojejunal anastomosis
for the laparoscopic isolated Roux-en-Y gastric bypass is safe and effective.
Anastomotic stenosis occurs in approximately one quarter of patients, but it can
be managed well with endoscopic balloon dilatation.
PMID- 11004335
TI - Inferior head resection of the pancreas for intraductal papillary mucinous
tumors.
AB - BACKGROUND: Patients with intraductal papillary mucinous tumor have a favorable
prognosis after surgical treatment. When this neoplasm is located in the head of
the pancreas, resection has conventionally required pancreatoduodenectomy.
Although pancreatoduodenectomy can now be performed with a low mortality rate,
morbidity still occurs frequently. METHODS: Between November 1982 and January
1999, 38 intraductal papillary mucinous tumors of the pancreas were resected at
the Chiba University Hospital. Seven patients (18%) underwent inferior head
resection of the pancreas. In this preliminary study, the operative technique is
presented, and its efficacy in improvement of quality of life is evaluated.
RESULTS: Patients with intraductal papillary mucinous tumor underwent resection
with no perioperative mortality. After discharge from hospital, 6 patients who
underwent inferior head resection were still alive without recurrent disease
after a median follow-up of 3 years. However, 1 patient developed peritoneal
dissemination and died 18 months after inferior head resection. Patients had
regained 98% of preoperative weight 1 year after inferior head resection. N
benzoyl-L-tyrosyl-p-amino-benzoic acid (BT-PABA) excretion test showed the same
value before (73%) and after (73%) inferior head resection (n = 7). Pancreatic
fistulas occurred more frequently after inferior head resection (38%), but the
incidence of major complications was similar between inferior head resection and
other types of pancreatic head resection. CONCLUSIONS: Pancreatic function was
well preserved, and patients regained 98% of preoperative weight after inferior
head resection of the pancreas. The authors concluded that the limited
involvement of intraductal papillary mucinous tumors enables the surgeons to
perform inferior head resection of the pancreas.
PMID- 11004336
TI - Right colonic intussusception.
PMID- 11004337
TI - Visceral artery aneurysms as seen in a community hospital.
AB - BACKGROUND: Visceral artery aneurysm (VAA) is a rare but important form of
vascular pathology. METHODS: A retrospective chart review was performed for all
patients treated for VAAs from 1980 to 1998 at the Northern California Kaiser
Hospitals. RESULTS: Thirty-one patients with VAAs were treated, 11 men and 20
women with an average age of 60 years. The arteries involved were 15 splenic, 8
hepatic, 5 superior mesenteric branch, 1 left gastric, 1 gastroduodenal, and 1
left colic. Seventy-four percent of patients presented with acute abdominal pain
and/or shock secondary to aneurysm rupture. Angioembolization was performed in 9,
and 25 were treated surgically. There was no morbidity, and 1 death (3.2%).
CONCLUSIONS: Patients with VAAs often present to the community hospital general
surgeon as acute abdominal emergencies. Symptomatic VAAs can be managed
successfully by simple ligation in the primary care setting.
PMID- 11004338
TI - Perfusion and functional anatomy of the splenic remnant supplied by short gastric
vessels.
AB - BACKGROUND: Surgeons have described many methods to preserve the injured spleen
for the maintenance of host defence. The volume and the perfusion of remaining
splenic tissue are important for better functional results. Imaging the
functioning tissue with radionuclide provides information about the physiology of
the concerning organ. METHODS: Thirty rats were separated into three groups:
control, explorative laparotomy alone; partial splenectomy, upper part of the
spleen supplied by short gastric vessels was preserved after partial resection;
and devascularized spleen, the entire spleen was preserved after ligation of
splenic artery. The size, functional anatomy, and perfusion status of splenic
tissue were assessed by liver-spleen scintigraphy using radiolabeled heat
denatured red blood cells. RESULTS: In the partial splenectomy group, splenic
radioactivity count, spleen/liver ratio, and radionuclide uptake were mildly
reduced, and found to be 87% (P = 0.012), 91% (P = 0.16), and 88% (P <0.001) of
the normal spleen, respectively. The area of functional tissue in the upper
splenic remnant was 51% (P <0.001) of the normal spleen. In the devascularized
spleen group, the radioactivity count, the ratio, and the uptake were 38% (P <10(
6)), 36% (P <10(-6)), and 49% (P <10(-6)) of the normal spleen respectively. The
area of functional tissue in the devascularized spleen was calculated as 47% (P
<10(-6)) of the normal spleen. CONCLUSIONS: The collateral circulation is
insufficient for proper function of the entire spleen after disconnection of the
main arterial blood supply. The functional tissue is markedly impaired. On the
other hand, the upper part of the spleen is remained well perfused via the short
gastric vessels. The collateral circulation is satisfactory for this splenic
tissue after reduction of its volume. That size splenic tissue seems to have
satisfactory functional ability. Proper functional results mostly depend on the
balance between the volume and blood supply of the remaining splenic tissue.
PMID- 11004339
TI - Ligating the cystic duct in laparoscopic cholecystectomy.
AB - BACKGROUND: In laparoscopic cholecystectomy, bile leak from the cystic duct stump
is a recognised postoperative complication. This could be due to dislodgement of
the metal clips. Migration of the clip is an added problem. METHODS: Since 1995,
70 patients were included in the study of intracorporeal cystic duct ligation in
laparoscopic cholecystectomy. Construction of a ligature is a single handed
procedure using a free end of the thread. It is quite different from the other
two methods described in the literature. RESULTS: There was not a single case of
postoperative morbidity in these patients, but in a retrospective study,
postoperative biliary dyspepsia with fatty food was evident in a few patients
among those cases in which the liga-clips were applied to the cystic duct.
CONCLUSION: The cystic duct ligation with absorbable thread should be a gold
standard in laparoscopic cholecystectomy. It reduces the risk of postoperative
morbidity.
PMID- 11004340
TI - Bilateral Jejuno-mesenteric flap for reconstruction of complicated
pharyngoesophageal defect.
AB - The surgical management of an infectious and fistulous wound with a
pharyngoesophageal tumor is one of the greatest challenges for head and neck and
plastic surgeons. The free jejunal transfer has been the standard technique for
pharyngoesophageal reconstruction, and the free omental flap has been one of the
most reliable methods for reconstructing contaminated wounds. A jejuno-mesenteric
flap is suitable for such complicated wounds. Pharyngoesophageal defects are
reconstructed by the jejunum, and contaminated and heavily irradiated neck wounds
are covered with the mesenteric flaps connected with a revascularized jejunum.
The technique described here possesses the advantages of both a free jejunal flap
and an omentum flap. Therefore, it is a reliable method for reconstructing the
pharyngoesophageal defects of complicated wounds.
PMID- 11004341
TI - Laparoscopic colorectal cancer surgery.
AB - BACKGROUND: A number of controversies exist in the laparoscopic treatment of
colorectal cancer, and thus the technique has so far failed to gain widespread
acceptance throughout the United Kingdom. This review aims to discuss these
issues in the context of ongoing published trials, assessing both purported
advantages and disadvantages. METHODS: The United States National Library of
Medicine Medline database, and the Bath Information Data Service (BIDS) were
searched using keywords related to laparoscopic colorectal cancer surgery. Recent
surgical journals were also reviewed for relevant publications. Attempts have
been made to quote only the most recent work from institutions with multiple
publications using the same group of patients, in order to present the most
coherent picture. The data are presented as randomized controlled trials,
nonrandomized controlled studies, and series comprising more than 10 patients.
CONCLUSIONS: This review confirms that laparoscopic colorectal cancer surgery is
technically feasible. In addition patients lose less blood, have less
immunosuppression, and have shorter postoperative ileus, in-patient stay, and
require less analgesia. However, concerns still remain as to the development of
port-site metastases, the longer operating times, and the overall cost of the
equipment. In view of these concerns, the place of laparoscopically assisted
colorectal cancer surgery is likely to remain controversial for some years yet.
Randomized, controlled trials are as yet too few to provide definitive answers to
all these issues.
PMID- 11004342
TI - The role of multimodality therapy for resectable esophageal cancer.
AB - BACKGROUND: There is an increasing interest in the role of combined therapy to
achieve long-term survival for patients with resectable esophageal neoplasms.
Surgery provides excellent palliation with relatively low morbidity and mortality
rates, but cure remains elusive. MATERIAL AND METHODS: From January 1988 to
January 1998, a total of 137 patients met eligibility criteria for a combined
multimodal therapy, prospective, nonrandomized protocol of induction
chemoradiation therapy followed by surgical resection, based on radiological and
endoscopic assessment of the extension (all patients were initially considered to
be at clinical stages I to III, locoregional). Consequently, patients with high
grade Barrett's dysplasia or any squamous carcinoma in situ (stage 0) and those
with distant metastatic disease (stage IV) were excluded. Among this group, 48
operable patients with biopsy-proven esophageal cancer finally entered and
completed the protocol and are the sample of the present study. Multivariate
logistic regression models were used to identify risk factors for death or
recurrence. Actuarial survival was calculated since the beginning of the
induction protocol by the Kaplan-Meier method, and comparisons between groups
were made by the log-rank test. RESULTS: Mean age was 61.6 (range 45 to 71), and
72.9% were male. The majority of the tumors (70.8%) were located at the lower
third/cardia and as many as 18.8% were adenocarcinoma. After a mean of 7.5 weeks
(range 5 to 12) after the completion of the induction phase, 68.7% underwent a
transthoracic esophagectomy and 31.3% a transhiatal esophagectomy. The in
hospital mortality rate was 10.4% (5 patients). A complete response (no evidence
of tumor within the specimen: pT0) was achieved in 25% (12 patients). After a
mean follow-up of 20.2 months, mean survival for the entire group was 18.2 months
(95% confidence interval 14 to 22). At the end of the study, 25% (12) remained
alive. Actuarial survival rates at 12, 23, and 37 months were 56.2%, 36.9%, and
21.9%, respectively. CONCLUSIONS: Esophageal resection after induction therapy
seems to be related to a slightly higher mortality rate compared with historical
series, and for this reason, neoadjuvant therapy must be considered still
experimental. However, no statistical significant difference in survival is
showed in those cases with complete pathological response (pT0). Factors
influencing survival are recurrence and age. Surgery alone remains the standard
therapy for esophageal cancer.
PMID- 11004344
TI - A prognostic score for gastric cancer.
AB - BACKGROUND: Scoring systems are generally used for predicting prognosis in the
intensive care unit, but there is no score being used frequently for predicting
prognosis in gastric cancer. The aim of this study was to develop a prognostic
score for gastric cancer patients. METHODS: Demographic, clinical, laboratory,
radiologic, histopathologic data, and operative findings for 128 patients who had
curative or palliative resection for gastric cancer were analyzed for their
effect on overall and disease-free survival. Ten variables-invasion depth of
tumor, node status (American Joint Committed on Cancer, 1992), metastasis, node
status (Union Internationale Contre le Cancer, 1997), metastatic lymph node
ratio, resectability, tumor location, extent of lymphadenectomy, Borrmann type,
Lauren type-that have independent significant effect or borderline significance
on both overall and disease-free survival according to multivariate analysis were
chosen. Coefficients were calculated for these variables by using Cox regression
analysis, and thus the Prognostic Score for Gastric Cancer (PSGC) was designed.
All patients were scored using the PSGC and also staged clinically (AJCC 1992)
and histopathologically (AJCC 1992 and UICC 1997). RESULTS: Patients were grouped
according to their scores: group 1, patients with scores 20 to 50 (probability of
5-year overall survival 50% to 95%); group 2, patients with scores 51 to 80
(probability of 5-year overall survival 10% to 50%); and group 3, patients with
scores 81 and higher (probability of 5-year overall survival <10%). Overall
survival and disease-free survival decreased significantly with increasing
scores. The association of PSGC and staging systems with survival was analyzed by
stepwise logistic regression and Cox regression analyses. PSGC was proved to have
the most significant association with overall and disease-free survival.
CONCLUSIONS: Inclusion of more variables in PSGC seems to make it superior than
staging. It is easy to adapt PSGC to different patient populations, which may
make it accepted as a practical and useful scoring system in clinical practice.
PMID- 11004343
TI - Is MIB-1 proliferation index a predictor for response to neoadjuvant therapy in
patients with esophageal cancer?
AB - BACKGROUND: The overall survival rate for patients with an esophageal cancer
remains poor. As a consequence, preoperative chemoradiation was introduced for
patients with tumor stage T >1 M0 regardless of tumor histology or localization.
However, factors predicting response to this therapy pretherapeutically are
largely unknown. METHODS: Clinical results of preoperative chemoradiation were
investigated. The rates of proliferation and apoptosis were determined in
pretherapeutic tumor samples and correlated with tumor response and long-term
survival after surgery. RESULTS: A complete tumor response due to chemoradiation
(n = 42; cervically localized tumors excluded) was achieved in 11 patients (26%)
after resection. Five-year survival rate was significantly improved in these
patients compared with those who did not respond to chemoradiation (48% versus
5.5%; P = 0.003). Chemoradiation was performed without benefit in 43%.
Perioperative hospital mortality rate was 14.3% in all patients. No correlation
of apoptosis with response to chemoradiation or postoperative long-term survival
was observed. However, there was a clear correlation between the proliferation
rate as determined by MIB-1 immunohistology. Five-year survival rate of patients
with a proliferation index (PI) >/=39% was 38% compared with 0% in tumors with a
PI <39%. Tumors with a PI >/=39% responded to chemoradiation in 71.4%, but 100%
of tumors with a PI <39% did not. Mean survival time of these patients was 33
months and 11 months, respectively (P = 0.015). CONCLUSIONS: The results indicate
that the PI may be used for stratification of patients treatment prior surgery.
However, these results need further validation in larger patient numbers in the
search for factors indicating response pretherapeutically to preoperative
chemoradiation in esophageal cancer.
PMID- 11004345
TI - Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed
offspring.
AB - OBJECTIVE: To evaluate long-term pregnancy experiences of women exposed to
diethylstilbestrol (DES) in utero compared with unexposed women. METHODS: This
study was based on diethylstilbestrol-exposed daughters, the National
Collaborative Diethylstylbistrol Adenosis cohort and the Chicago cohort, and
their respective nonexposed comparison groups. Subjects who could be traced were
sent a detailed questionnaire in 1994 that contained questions on health history,
including information on pregnancies and their outcomes. We reviewed 3373
questionnaires from exposed daughters and 1036 questionnaires from unexposed
women. RESULTS: The response rate was 88% among exposed and unexposed women.
Diethylstilbestrol-exposed women were less likely than unexposed women to have
had full-term live births and more likely to have had premature births,
spontaneous pregnancy losses, or ectopic pregnancies. Full-term infants were
delivered in the first pregnancies of 84.5% of unexposed women compared with 64.
1% of exposed women identified by record review (relative risk [RR] 0.76,
confidence interval [CI] 0.72, 0.80). Preterm delivery of first births occurred
in 4.1% of unexposed compared with 11.5% of exposed women, and ectopic
pregnancies in 0.77% of unexposed compared with 4.2% of exposed women.
Spontaneous abortion was reported in 19.2% of DES-exposed women compared with
10.3% in control women (RR 2.00, CI 1.54, 2.60). According to complete pregnancy
histories (many women had more than one pregnancy), preterm births were more
common in DES-exposed women (19.4% exposed versus 7.5% unexposed (RR 2.93 CI
2.23, 3.86). Second-trimester spontaneous pregnancy losses were more common in
DES-exposed women (6.3% versus 1.6%; RR 4.25, CI 2.36, 7.66). More first
trimester spontaneous abortions occurred in DES-exposed women than in controls
(RR 1.31, CI 1.13, 1.53), and DES-exposed women had at least one ectopic
pregnancy more often than unexposed women (RR 3.84, CI 2.26, 6.54). CONCLUSION:
Pregnancy outcomes in DES-exposed women were worse than those in unexposed women.
PMID- 11004346
TI - Serial salivary estriol to detect an increased risk of preterm birth.
AB - OBJECTIVE: To evaluate serial measurements of salivary estriol (E3) to detect
increased risk of spontaneous preterm labor and preterm birth. METHODS: A masked,
prospective, multicenter trial of 956 women with singleton pregnancies was
completed at eight United States medical centers. Saliva was collected weekly,
beginning at the 22nd week of gestation until birth, and tested for unconjugated
E3 by enzyme-linked immunosorbent assay. Women were separated into high-risk and
low-risk groups using the Creasy scoring system. RESULTS: A single, positive (at
or above 2.1 ng/mL) salivary E3 test predicted an increased risk of spontaneous
preterm labor and delivery in the total population (relative risk [RR] 4.0, P
<.005), in the low-risk population (RR 4.0, P < or =.05), and in the high-risk
population (RR 3.4, P =.05). Two consecutive positive tests significantly
increased the RR in all study groups, with a dramatic improvement in test
specificity and positive predictive value but only a modest decrease in
sensitivity. In women who presented with symptomatic preterm labor, salivary E3
identified 61% of those who delivered within 2 weeks, using a threshold of 1.4
ng/mL. CONCLUSION: Elevated salivary E3 is associated with increased risk of
preterm birth in asymptomatic women and symptomatic women who present for
evaluation of preterm labor.
PMID- 11004347
TI - Group B streptococcal colonization and serotype-specific immunity in pregnant
women at delivery.
AB - OBJECTIVE: To describe the relationship between serum concentration of group B
streptococcal capsular polysaccharide-specific immunoglobulin (Ig) G,
colonization status, race or ethnicity, and age in pregnant women. METHODS:
Pregnant women (n = 3307) were enrolled from geographically and ethnically
diverse populations. At the time of admission for delivery, swabs of the lower
vagina and rectum were obtained for isolation of group B streptococci. In a
subset of women whose sera were available, capsular polysaccharide-specific IgG
concentrations were quantified by serotype-specific (Ia, Ib, II, III, and V)
enzyme-linked immunosorbent assay and compared by group B streptococcal
colonization status. RESULTS: Group B streptococcal colonization was detected in
856 women (26%), and the rate was significantly higher among black women (37%)
than in other racial or ethnic groups (odds ratio 1.7, 95% confidence interval
1.4, 2.1). Colonization status did not differ by study site or age. Colonization
with serotypes Ia, II, III, or V was associated with significantly higher serum
concentrations of IgG specific for the capsular polysaccharide of the colonizing
serotype compared with noncolonization. However, 48% of colonized women had low
capsular polysaccharide-specific IgG levels (less than 0.5 microg/mL) in their
delivery sera. Colonized teenagers had the lowest median concentration.
CONCLUSION: Colonization with group B streptococcus can elicit a systemic immune
response, with a cumulative increase in the prevalence of capsular polysaccharide
specific IgG with increasing age. Conversely, low antibody levels in colonized
teenagers might account in part for the reported increased risk of group B
streptococcal disease in neonates born to these patients.
PMID- 11004348
TI - Wet smear compared with gram stain diagnosis of bacterial vaginosis in
asymptomatic pregnant women.
AB - OBJECTIVE: To compare wet smear and Gram stain diagnoses of bacterial vaginosis
among asymptomatic pregnant women. METHODS: Between November 1, 1996 and December
31, 1997, asymptomatic women who initiated prenatal care in our obstetric clinics
were invited to participate. Exclusion criteria included antimicrobial use within
2 weeks, cervical cerclage, vaginal bleeding, placenta previa, spermicide use,
douching, or intercourse within 8 hours. Clinical diagnosis that required two of
three positive criteria for bacterial vaginosis (vaginal pH, whiff test, and clue
cells on wet smear) was compared with Gram stain diagnosis (Bacterial vaginosis
score 7-10 by Nugent criteria). RESULTS: Population characteristics (n = 69)
included an average (+/- standard deviation [SD]) maternal age of 27. 3 +/- 6.6
years, 26 nulliparas (38%), 28 black women (41%), 23 white women (38%), 15
Hispanic women (22%), and three Asian women (4%). The mean (+/-SD) gestational
age at entry was 15.6 +/- 7.6 weeks. Twenty-seven percent (18 of 67) of the study
population was diagnosed with bacterial vaginosis by definitive Gram stain. Two
slides were lost or were of poor quality and not included. Using Gram stain
diagnosis of bacterial vaginosis as the standard, clinical diagnosis had
sensitivity of 56% (95% confidence interval [CI] 32%, 78%), a specificity of 96%
(95% CI 90%, 100%), a positive predictive value of 83%, and a negative predictive
value of 85%. CONCLUSION: In asymptomatic pregnant women, bacterial vaginosis can
be diagnosed reliably by Gram stain.
PMID- 11004349
TI - Relation between serum uric acid and plasma adenosine levels in twin pregnancies.
AB - OBJECTIVE: To examine the relationship between plasma adenosine and serum uric
acid levels in women with singleton and twin pregnancies. METHODS: We sampled
maternal arterial blood and measured serum uric acid and plasma adenosine levels
in 22 singleton pregnancies and nine twin pregnancies at 33 to 38 weeks'
gestation. RESULTS: The average plasma adenosine levels were 0.31 +/- 0.12
micromol/L in the singleton pregnancy group and 0.45 +/- 0.09 micromol/L in the
twin pregnancy group (P <.001). The mean serum uric acid level in women with twin
pregnancy was 5.7 +/- 0.44 mg/dL which was higher than that in the singleton
pregnant women (4.4 +/- 0.69 mg/dL, P <.001). Positive correlations were found
between serum uric acid and plasma adenosine levels in both the singleton (r(2) =
0.54, P <.001) and the twin pregnancy groups (r(2) = 0.65, P =.009). Moreover,
there was also a significant correlation between serum uric acid and plasma
adenosine levels overall (r(2) = 0.66, P <.001). CONCLUSION: Our results suggest
that higher adenosine levels are a contributing source of hyperuricemia in twin
pregnancies.
PMID- 11004350
TI - Procedure-related miscarriages and Down syndrome-affected births: implications
for prenatal testing based on women's preferences.
AB - OBJECTIVE: To determine how pregnant women of varying ages, races, ethnicities,
and socioeconomic backgrounds value procedure-related miscarriage and Down
syndrome-affected birth. METHODS: We studied cross-sectionally 534
sociodemographically diverse pregnant women who sought care at obstetric clinics
and practices throughout the San Francisco Bay area. Preferences for procedure
related miscarriage and the birth of an infant affected by Down syndrome were
assessed using the time trade-off and standard gamble metrics. Because current
guidelines assume that procedure-related miscarriage and Down syndrome-affected
birth are valued equally, we calculated the difference in preference scores for
those two outcomes. We also collected detailed information on demographics,
attitudes, and beliefs. RESULTS: On average, procedure-related miscarriage was
preferable to Down syndrome-affected birth, as evidenced by positive differences
in preference scores for them (time trade-off difference: mean = 0.09, median =
0.06; standard gamble difference: mean = 0.11, median = 0.02; P <.001 for both,
one-sample sign test). There was substantial subject-to-subject variation in
preferences that correlated strongly with attitudes about miscarriage, Down
syndrome, and diagnostic testing. CONCLUSION: Pregnant women tend to find the
prospect of a Down syndrome-affected birth more burdensome than a procedure
related miscarriage, calling into question the equal risk threshold for prenatal
diagnosis. Individual preferences for those outcomes varied profoundly. Current
guidelines do not appropriately consider individual preferences in lower-risk
women, and the process for developing prenatal testing guidelines should be
reconsidered to better reflect individual values.
PMID- 11004351
TI - Complications of hysteroscopic surgery: predicting patients at risk.
AB - OBJECTIVE: To determine the frequency of operative complications and whether they
can be predicted by specific patient characteristics or type of hysteroscopic
procedure. METHODS: We collected demographic and medical history information on
925 women who had hysteroscopies from 1995 through 1996. We compared differences
in rates of operative complications of specific hysteroscopic procedures.
Operative complications were defined as uterine perforation, excessive glycine
absorption (1 L or more), hyponatremia, hemorrhage (500 mL or more), bowel or
bladder injury, inability to dilate the cervix, and procedure-related hospital
admissions. RESULTS: Operative complications occurred in 25 (2.7%) of 925
hysteroscopies. Excessive fluid absorption was the most frequent complication.
Hysteroscopic myomectomy and resection of uterine septum were associated with
greater odds of complications (odds ratio [OR] 7.4, 95% confidence interval [CI]
3.3, 16.6 and OR 4.0, 95% CI 0.9, 19.6, respectively). Hysteroscopic polypectomy
and endometrial ablation were associated with lower odds of complications (OR
0.1, 95% CI 0.0, 0.7 and OR 0.4, 95% CI 0.1, 3.3, respectively). Hysteroscopies
done by reproductive endocrinologists and preoperative GnRH agonist therapy were
associated with 4-7 times higher odds for operative complications. CONCLUSION:
Complications during hysteroscopic surgery are rare. Among hysteroscopic
procedures, myomectomies and resections of uterine septa have significantly
higher rates of complications, especially excessive fluid absorption. Meticulous
fluid management might limit the number of serious complications of these higher
risk procedures.
PMID- 11004352
TI - Eicosapentaenoic acid effect on hyperlipidemia in menopausal Japanese women. The
Niigata Epadel Study Group.
AB - OBJECTIVE: To assess the efficacy and safety of eicosapentaenoic acid for the
treatment of hyperlipidemia in symptomatic menopausal Japanese women. METHODS: We
performed a prospective observational 48-week study in hyperlipidemic menopausal
women. We randomly assigned 141 women, whose levels of serum total cholesterol
were 220 to 280 mg/dL or whose serum triglycerides were 150 to 400 mg/dL at
baseline to groups treated with estriol (E3) 2 mg daily (control group, n = 72)
or ethyl icosapentate 1800 mg daily and E3 2 mg (eicosapentaenoic acid group, n =
69). RESULTS: Serum levels of total cholesterol decreased significantly from
249.4 to 238.6 mg/dL (-4.3%, P =.003) in the control group and from 252.3 to
234.0 mg/dL (-7.3%, P =.001) in the study group at week 48 in the women whose
total cholesterol was not less than 220 mg/dL at baseline. Serum levels of
triglycerides decreased significantly from 194.5 to 141.5 mg/dL (-27. 2%, P
=.001) in the study group but increased slightly from 192.9 to 207.4 mg/dL
(+7.5%) in the control group at week 48 in the women whose level of triglycerides
was not less than 150 mg/dL. There were significant differences between these two
groups at weeks 12, 24, and 48. Serum levels of total cholesterol and
triglycerides were significantly decreased at week 48 in the study group
regardless of whether the women were obese. There were no severe adverse effects.
CONCLUSION: Combination therapy with eicosapentaenoic acid and E3 was effective
and safe for menopausal women with hypertriglyceridemia.
PMID- 11004353
TI - Safety of extraovular catheter insertion for second-trimester abortion.
AB - OBJECTIVE: To evaluate the efficacy and safety of second-trimester abortions
using transcervical catheter insertion and extraovular prostaglandin (PG)
administration. METHODS: Ninety women admitted for terminations of pregnancy at
17-24 weeks' gestation had transcervical catheters inserted and extraovular
PGE(2) administered. Success rates were recorded, measured by induction of
abortion within 24 hours, need for a complement uterine curettage, and
complications. RESULTS: The technique induced abortion in 67 women (74.4%). The
induction-to-abortion median interval was 12 hours (7 and 22 hours, fifth and
95th percentiles, respectively). Thirty-seven women needed uterine curettages
because of incomplete abortions or excessive uterine bleeding after fetal and
placenta expulsion. One woman had shivering, weakness, and nausea attributed to
systemic absorption of PG, and nine women developed systemic inflammatory
response syndrome associated with transcervical catheter insertion. Two of those
women had septic shock, one of whom deteriorated to a life-threatening situation.
CONCLUSION: Transcervical catheter insertion for extraovular PG administration is
effective for inducing second-trimester abortions. Although the method is
considered safe, with generally few mild, treatable complications, we observed a
high rate of systemic inflammatory response syndrome, bacteremia, and sepsis
caused by transcervical catheter insertion before PG administration. A
reconsideration of this method's safety is warranted.
PMID- 11004354
TI - Prelabor rupture of the membranes at term: expectant management at home or in
hospital? The TermPROM Study Group.
AB - OBJECTIVE: To determine whether adverse effects of expectant management for
premature rupture of membranes (PROM) at term and patient satisfaction were
greater if women were managed at home rather than in a hospital. METHODS: We
undertook a secondary analysis of data from the International TermPROM Study for
women managed expectantly at home or in a hospital. Using multiple logistic
regression analyses, we determined the effect of home and hospital management and
controlled for differences in baseline characteristics, in measures of maternal
and neonatal infections and rates of cesarean. RESULTS: Six hundred fifty-three
women (39.1%) were managed at home, and 1017 (60.9%) in a hospital. Management at
home, compared with in a hospital, increased risk of nulliparas needing
antibiotics before delivery (odds ratio [OR] 1.52 95% confidence interval [CI]
1.04, 2.24, P =.03), those not colonized with group B streptococcus having
cesareans (OR 1.48 95% CI 1.03, 2. 14, P =.04), and neonatal infections (OR 1.97
95% CI 1.00, 3.90, P =. 05). More multiparas managed at home said they would
participate in the study again (OR 1.80 95% CI 1.27, 2.54, P <.001). CONCLUSION:
Expectant management at home, rather than in a hospital, might increase the
likelihood of some adverse outcomes.
PMID- 11004355
TI - Membrane sweeping in conjunction with labor induction.
AB - OBJECTIVE: To determine whether cervical membrane sweeping (stripping) during
induction of labor is beneficial. METHODS: We compared outcomes of labor after
induction in pregnant women at term in a randomized trial. Women were assigned to
having their membranes swept or not during induction. Outcome measures included
duration of labor, maximum dose of oxytocin used, induction-labor interval, and
mode of delivery. RESULTS: We recruited 130 nulliparas (64 sweep, 66 nonsweep)
and 118 multiparas (60 sweep, 58 nonsweep). Among nulliparas who received
intravaginal prostaglandin (PG) E(2) and oxytocin, those who had simultaneous
sweeping had significantly shorter mean (+/- standard error of mean) induction
labor interval (13.6 +/- 1.4 versus 17.3 +/- 1.2 hours, P =.048), lower mean
maximum dose of oxytocin (6.8 +/- 0.8 versus 10.35 +/- 1.1 mU/minute, P =.01),
and increased normal delivery rates (vaginal delivery 83. 3% versus 58.2%, P
=.01). Sweeping also had a favorable effect on nulliparas who received oxytocin
alone (mean induction-labor interval 5.8 +/- 3.1 versus 11.2 +/- 3.6 hours, P
=.04; mean maximum dose 8.8 +/- 1.3 versus 16.3 +/- 1.9 mU/min, P =.01). Those
differences were limited to women with unfavorable cervices. There were no
differences in any outcome measures in multiparous women. CONCLUSION: Sweeping of
the membranes during induction of labor had a beneficial effect on labor and
delivery, which appeared to be limited to nulliparas with unfavorable cervices
who needed cervical priming with PGE(2).
PMID- 11004356
TI - Mifepristone for preinduction cervical ripening beyond 41 weeks' gestation: a
randomized controlled trial.
AB - OBJECTIVE: To compare the effect of mifepristone with placebo on cervical
ripening before labor induction in prolonged pregnancies. METHODS: One hundred
eighty women with pregnancies beyond 41 weeks and undilated, uneffaced cervices
were assigned randomly to receive mifepristone 200 mg or placebo and observed for
24 hours. We then gave intravaginal misoprostol 25 microg every 4 hours or
intravenous oxytocin. We expected 60% of placebo-treated and 80% of mifepristone
treated women to deliver vaginally within 48 hours. RESULTS: Among 180 subjects,
97 received mifepristone and 83 received placebo. The mean interval (+/- standard
deviation [SD]) from start of induction to delivery was 2209 +/- 698 minutes for
mifepristone-treated subjects and 2671 +/- 884 minutes for placebo-treated
subjects (P <.001, log-transformed data). Twelve (13. 6%) mifepristone-treated
women and seven (10.8%) placebo-treated women delivered vaginally on day 1 (P
=.60). After 24 hours, the median Bishop score for both groups was 3 (0-11) (P
=.51). One hundred thirty-one subjects required misoprostol, 65 (67.0%) were
mifepristone-treated women, and 66 (79.5%) placebo-treated women (P =.06). The
median (range) oxytocin dose was 871.5 (0-22,174) mU for mifepristone-treated
women and 2021.0 (0-24,750) mU for placebo-treated women (P =.02). Seventy-seven
(87.5%) mifepristone-treated women and 46 (70.8%) placebo-treated women delivered
vaginally 48 hours after the start of treatment (P =.01). There were nine
cesareans in the mifepristone group and 18 in the placebo group (P =.02). More
nonreassuring fetal heart rate patterns and uterine contractile abnormalities
occurred in mifepristone-treated subjects. There were no statistically
significant differences in neonatal outcomes between groups. CONCLUSION:
Mifepristone had a modest effect on cervical ripening when given 24 hours before
labor induction, appearing to reduce the need for misoprostol and oxytocin
compared with placebo.
PMID- 11004357
TI - Randomized comparison of glyceryl trinitrate and prostaglandin E2 for cervical
ripening at term.
AB - OBJECTIVE: To estimate the adverse effects of glyceryl trinitrate compared with
prostaglandin (PG) E2 vaginal tablet for cervical ripening in term pregnancy.
METHODS: One hundred ten women with term pregnancies referred for induction of
labor with Bishop scores of 6 or less were randomly assigned to receive a 500
microg glyceryl trinitrate tablet vaginally (n = 54) or a 3-mg PGE2 tablet
vaginally (n = 56), every 6 hours for maximum of two doses. Subjects were sent to
the labor ward for amniotomy or oxytocin if their Bishop scores were more than 6
or their cervices were not ripe 24 hours after treatment. Adverse effects,
changes in the Bishop scores, progress, and outcomes of labor were assessed.
RESULTS: Glyceryl trinitrate was associated with fewer episodes of uterine
tachysystole (0% versus 9%; P =.02). The median Bishop score after 12 hours was
lower in women given glyceryl trinitrate compared with those given PGE2. Adverse
effects, including headache and palpitations, were more frequent with glyceryl
trinitrate than with PGE2. The cesarean rate was not significantly different
between groups. CONCLUSION: Cervical ripening with glyceryl trinitrate resulted
in fewer episodes of tachysystole, but there were significantly more minor side
effects. It can be used for cervical ripening at term, but it was not as
effective as PGE2.
PMID- 11004358
TI - Ultrasonography for cervical length measurement: agreement between transvaginal
and translabial techniques.
AB - OBJECTIVE: To assess agreement between transvaginal and translabial
ultrasonography for measuring cervical length in the second and third trimesters.
METHODS: Eighty-four obstetric patients at 14-40 weeks' gestation were enrolled.
Three images of the cervix were obtained by translabial (3.5-MHz curvilinear
transducer) and transvaginal (6.5-MHz endovaginal probe) ultrasonography. The
mean cervical length obtained by using each method was used for data analysis.
The McNemar chi(2) test was used to assess the difference between techniques in
their ability to obtain a measurement. The paired t-test was used to evaluate the
differences between the measurements. The mean difference and SD for the
differences were used to calculate the limits of agreement. An acceptable
difference was defined as less than 0.5 cm. RESULTS: Cervical length measurements
were obtained in 84 patients (100%) by using the transvaginal technique and in 80
patients (95%) by using the translabial technique (P =.1). Eighty patients had
both transvaginal and translabial measurements for comparison. The mean
difference in cervical length was 0.37 cm (P <.001; 95% confidence interval [CI]
0. 21, 0.52). The upper and lower limits of agreement were 1.75 cm (95% CI 1.48,
2.02) and -1.01 cm (95% CI -0.74, -1.28), respectively. The differences between
the two measurements were within these limits 95% of the time. These limits of
agreement were greater than the acceptable difference of 0.5 cm. CONCLUSION:
Transvaginal and translabial techniques should not be used interchangeably for
clinical assessment of cervical length because agreement between the methods is
not within an acceptable range.
PMID- 11004359
TI - One-stage screening for pregnancy complications by color Doppler assessment of
the uterine arteries at 23 weeks' gestation.
AB - OBJECTIVE: To estimate the value of screening for preeclampsia and fetal growth
restriction by performing color Doppler assessment of uterine arteries at 23
weeks' gestation in predicting adverse pregnancy outcome. METHODS: Women with
singleton pregnancies who attended routine ultrasonography at 23 weeks had color
Doppler uterine artery imaging. Bilateral uterine artery notches were noted and
left and right uterine artery pulsatility indices (PI) were measured. A mean PI
of more than 1.45 was considered increased. Screening characteristics for
predicting preeclampsia and delivery of small-for-gestational-age infants were
calculated. RESULTS: Of 1757 pregnancies, increased PI was present in 89 (5.1%)
and bilateral notches were noted in 77 (4.4%). Twenty-three of 65 women (35.3%;
95% confidence interval [CI] 23.9, 48.2) had increased PI and later developed
preeclampsia, and 8 of 10 (80%; 95% CI 44.4, 97. 5) with preeclampsia required
delivery before 34 weeks. The respective values for women with bilateral notches
were 21 of 65 (32. 3%; 95% CI 21.2, 45.1) and 8 of 10 (80%; 95% CI 44.4, 97.5).
The sensitivity of increased PI was 30 of 143 (21%; 95% CI 14.6, 28.6) for
delivery of an infant with birth weight below the tenth percentile and 7 of 10
(70% 95% CI 34.8,93.3) for birth weight below the tenth percentile delivered
before 34 weeks. The respective values for bilateral notches were 19 of 143
(13.3%; 95% CI 8.2, 20) and 5 of 10 (50%; 95% CI 18.7, 81.3). CONCLUSION: A one
stage color Doppler screening program at 23 weeks identified most women who
subsequently developed serious complications of impaired placentation associated
with delivery before 34 weeks. The screening results were similar when the high
risk group was defined as women with increased PI or bilateral notches.
PMID- 11004360
TI - Maximal exercise testing in late gestation: fetal responses.
AB - OBJECTIVE: To determine the fetal response to and safety of maximal maternal
exercise in the third trimester. METHODS: Twenty-three active women with
uncomplicated pregnancies (singleton gestations) underwent maximal exercise
testing in late gestation using a progressive maximal cycle ergometer protocol.
Fetal heart rate (FHR) responses were monitored and classified using National
Institute of Child Health and Human Development guidelines. Statistical analyses
involved use of the Student t test, repeated measures analysis of variance with
Tukey-Kramer multiple comparisons posttest, and the chi(2) test. RESULTS: There
was an increase in baseline FHR in the 20-minute posttest period compared with
the 20-minute pretest period. There were significantly fewer accelerations in the
second posttest 10-minute segment compared with the second pretest 10-minute
segment. Variability was reduced in both posttest periods compared with the first
10-minute pretest period. Time to reactivity increased after testing. Mild
tachycardia was noted in two tracings and bradycardia occurred in a fetus with
previously undiagnosed growth restriction. There were no abnormal neonatal
outcomes. CONCLUSION: Maximal exercise testing in late gestation led to minimal
changes in FHR. Fetal bradycardiac responses were not seen in appropriate for
gestational age fetuses, suggesting that brief maximal maternal exertion for
research or diagnostic purposes is safe in this group.
PMID- 11004361
TI - Randomized trial of intermittent or continuous amnioinfusion for variable
decelerations.
AB - OBJECTIVE: To determine whether continuous or intermittent bolus amnioinfusion is
more effective in relieving variable decelerations. METHODS: Patients with
repetitive variable decelerations were randomized to an intermittent bolus or
continuous amnioinfusion. The intermittent bolus infusion group received boluses
of 500 mL of normal saline, each over 30 minutes, with boluses repeated if
variable decelerations recurred. The continuous infusion group received a bolus
infusion of 500 mL of normal saline over 30 minutes and then 3 mL per minute
until delivery occurred. The ability of the amnioinfusion to abolish variable
decelerations was analyzed, as were maternal demographic and pregnancy outcome
variables. Power analysis indicated that 64 patients would be required. RESULTS:
Thirty-five patients were randomized to intermittent infusion and 30 to
continuous infusion. There were no differences between groups in terms of
maternal demographics, gestational age, delivery mode, neonatal outcome, median
time to resolution of variable decelerations, or the number of times variable
decelerations recurred. The median volume infused in the intermittent infusion
group (500 mL) was significantly less than that in the continuous infusion group
(905 mL, P =.003). CONCLUSION: Intermittent bolus amnioinfusion is as effective
as continuous infusion in relieving variable decelerations in labor. Further
investigation is necessary to determine whether either of these techniques is
associated with increased occurrence of rare complications such as cord prolapse
or uterine rupture.
PMID- 11004362
TI - Management strategy for fetal tachycardia.
AB - OBJECTIVE: To develop a management strategy for fetal tachycardia. METHODS: Forty
four fetuses (20-40 weeks' gestation) with nonsinus tachycardia were divided into
three groups based on duration of tachycardia and degree of heart failure.
Fetuses with intermittent tachycardia were treated expectantly. Fetuses with
sustained tachycardia were treated with transplacental antiarrhythmic agents
alone if heart failure was mild to moderate, and with direct intramuscular
therapy if heart failure was severe. Degree of heart failure was determined by
echocardiographic variables of ventricular function, atrioventricular valve
insufficiency, and hydrops. Fetal well-being and response to treatment were
evaluated by daily heart rate surveillance and frequent fetal echocardiograms and
ultrasounds. RESULTS: Fifteen fetuses with intermittent tachycardia (n = 15,
group 1) did not progress to sustained tachycardia or heart failure. Fetuses with
sustained tachycardia and mild-to-moderate heart failure (n = 14, group 2) were
cardioverted or rate controlled with transplacental agents (n = 9); three term
fetuses were delivered electively without treatment and two progressed to severe
heart failure and were treated in group 3. Seventeen fetuses (15 initially, two
progressing) with severe heart failure were cardioverted (in 0. 25-21 days; mean
4.3 days) with fetal intramuscular plus transplacental antiarrhythmic therapy
(group 3). Overall, 43 of 44 fetuses were delivered at 32 to 41 (mean 37) weeks
with minimal morbidity and a mortality rate of 2.2% (95% confidence interval 0.
06%, 12.0%). CONCLUSION: Perinatal mortality and morbidity were low after
following a management strategy based on duration of tachycardia, degree of heart
failure, and biophysical profile combined with vigilant ongoing fetal
surveillance.
PMID- 11004363
TI - Downregulation of a mitogen-activated protein kinase signaling pathway in the
placentas of women with preeclampsia.
AB - OBJECTIVE: To investigate whether the activity of the three mitogen-activated
protein kinases (Jun aminoterminal kinase, extracellular regulated kinase, and
p38) is altered in placental tissue of women with preeclampsia and hemolysis,
elevated liver enzymes, low platelets (HELLP) syndrome. METHODS: Placental
activity (measured by immunoprecipitation-kinase assay) and protein expression
(measured by western blot) of Jun aminoterminal kinase, extracellular regulated
kinase, and p38 mitogen-activated protein kinase were measured in four groups of
eight women each with preeclampsia, HELLP syndrome, and normal vaginal or
cesarean deliveries. To further characterize the Jun aminoterminal kinase signal
transduction pathway, phosphorylation of c-Jun, a downstream effector of Jun
aminoterminal kinase- mitogen-activated protein kinase, was analyzed by western
blotting, and the activity of Rac1, an upstream activator of the Jun
aminoterminal kinase signaling pathway, was determined by pull-down assay.
RESULTS: The activity of Jun aminoterminal kinase was significantly lower in
placentas of women with preeclampsia or HELLP syndrome compared with those who
had normal vaginal or cesarean delivery, whereas levels of Jun aminoterminal
kinase protein expression were similar. Phosphorylation of the transcription
factor c-Jun and Rac1 activity also were significantly lower in women with
preeclampsia and HELLP than in controls. p38 mitogen-activated protein kinase
activity was significantly higher in women with preeclampsia than with HELLP
syndrome. There was no change in extracellular regulated kinase activity or
protein expression between subgroups. CONCLUSION: In placentas of women with
preeclampsia or HELLP syndrome, a Rac1-Jun aminoterminal kinase-c-Jun-dependent
signal transduction pathway was downregulated.
PMID- 11004365
TI - Accuracy of the pelvic examination in detecting adnexal masses.
AB - OBJECTIVE: To estimate sensitivity, specificity, positive predictive value,
Youden J statistic, and likelihood ratio of pelvic examination in adnexal
assessment under ideal circumstances. METHODS: One hundred forty women consented
to have pelvic examinations under general anesthesia before laparoscopy or
laparotomy. They were assigned to examiners masked to indications for surgery,
including attending gynecologists, gynecology residents, and medical students.
Surgeons' findings were compared with examiners' findings. Variables assessed
included adnexal diameter, presence of adnexal masses, and effect modifiers such
as examiner experience and body mass index. RESULTS: Forty-nine left adnexal and
33 right adnexal masses were found during surgery. Examiners tended to
underestimate adnexal size. Sensitivity of pelvic examinations for detecting left
adnexal masses was 0.23-0.36 and for right adnexal masses was 0.15-0.28. Positive
predictive value was low for left adnexal masses (0.50-0. 69) and right adnexal
masses (0.26-0.39). Differences among examiner groups were not statistically
significant. Patient obesity noticeably reduced detection of adnexal masses on
either side. CONCLUSION: Bimanual pelvic examination has marked limitations for
evaluating adnexa, even with ideal circumstances. Experience during postgraduate
training in gynecology did not seem to improve examination accuracy. Patient
characteristics such as obesity, uterine size, and abdominal scars limit the
accurate palpation of the adnexa.
PMID- 11004364
TI - Alpha-fetoprotein and hematopoietic growth factors in amniotic fluid.
AB - OBJECTIVE: To determine whether a relationship exists between alpha-fetoprotein
(AFP) and hematopoietic growth factors in amniotic fluid. METHODS: Forty-one
women at 15 weeks' gestation were included in the study. Gestational age was
assessed by obtaining a reliable menstrual history and scanning. Amniocentesis
was performed, and each woman subsequently delivered anatomically and
chromosomally normal infants. The level of AFP was determined using a standard
automated procedure. The concentrations of stem cell factor, interleukin 3,
interleukin 6, erythropoietin, and granulocyte colony-stimulating factor (G-CSF)
were measured using a commercially available immunoassay. The relationships
between AFP and the studied cytokines were evaluated using the Pearson linear
correlation test. Significant correlations were studied further by linear and
nonlinear regression to obtain the best predictive model. RESULTS: There was a
significant correlation between AFP and stem cell factor (r =.47, P =.002). No
significant correlations between AFP and the rest of the studied cytokines were
found (r = -.07, r =.02, r = -.02, and r = -.11 for erythropoietin, G-CSF,
interleukin 3, and interleukin 6, respectively). CONCLUSION: Alpha-fetoprotein is
significantly correlated with stem cell factor in early pregnancy and might play
a role in fetal hematopoiesis.
PMID- 11004366
TI - Clinical presentation of enterocele.
AB - OBJECTIVE: To characterize preoperative signs and symptoms in women with and
without enteroceles. METHODS: Three hundred ten women completed preoperative
questionnaires and had prolapses graded according to the International Continence
Society system. Signs and symptoms in 77 women (25%) with enteroceles confirmed
at surgery were compared with those in 233 women without enteroceles. Comparisons
were tested for statistical significance with chi(2) tests, Fisher exact tests,
Wilcoxon rank-sum tests, and analysis of covariance. RESULTS: Women with
enteroceles were statistically significantly older (median 67 versus 59 years, P
<.001) and more likely to be postmenopausal (88% versus 76%, P =.04). More women
with enteroceles had histories of hysterectomies (76% versus 39%, P =.001) and
vaginal prolapse repairs (24% versus 11%, P =.008). Women with enteroceles had
more advanced prolapses at points Ap, Bp, and C (all P <.001) but not point D.
There were no significant differences in symptoms related to bowel function
(infrequent bowel movements, straining, manual evacuation, and fecal
incontinence) in women with and without enteroceles. Women with enteroceles were
more bothered by symptoms caused by vaginal prolapse than women without
enteroceles, but not after we controlled for stage of prolapse. CONCLUSION: Women
with enteroceles have more advanced apical and posterior vaginal prolapses than
women without enteroceles, but do not differ from them in bowel function.
PMID- 11004367
TI - Early feeding and the incidence of gastrointestinal symptoms after major
gynecologic surgery.
AB - OBJECTIVE: To compare early feeding with traditional postoperative dietary
management for development of postoperative gastrointestinal symptoms, including
ileus after major gynecologic surgery for benign conditions. METHODS: Women who
had major gynecologic surgery for benign conditions were randomly allocated to
early feeding of low residue diets 6 hours postoperatively or traditional dietary
management of clear liquids with normal bowel sounds, and regular diet with
passage of flatus. Demographic and perioperative data were collected, and
patients answered questionnaires on their perception of bowel function and pain
using the McGill Pain Scale. Power analysis found that 130 women were needed to
find a twofold greater incidence of ileus in the early feeding group with 80%
power and alpha =.05. RESULTS: Complete data were available for 139 women, 67
allocated to the early feeding group and 72 to the late feeding group. The
incidence of postoperative ileus for the study population was 4.4% and did not
differ between groups (early 3% versus late 5. 8%, P =.68). There were no
differences in patient demographics, surgical procedures, anesthesia used, and
intraoperative complications between groups. With the exception of more
complaints of nausea in the late feeding group (23% versus 13%, P =.04), there
were no differences in other postoperative variables, including other
perioperative complications, pain medicine requirements, fluid and caloric
intake, median pain scores, and gastrointestinal function. The low incidence of
perioperative complications made the power to detect differences between groups
low. CONCLUSION: Low residue diet 6 hours after major gynecologic surgery for
benign indications was not associated with increased postoperative
gastrointestinal complaints, including ileus.
PMID- 11004368
TI - Physical activity and reduced risk of ovarian cancer.
AB - OBJECTIVE: To examine the relation between leisure-time physical activity and
ovarian cancer. METHODS: We used data from a population based case-control study.
Cases (n = 767) were women 20-69 years of age in whom epithelial ovarian cancer
was diagnosed during 1994-1998 and who resided in a defined region of
Pennsylvania, New Jersey, or Delaware. Controls (n = 1367) were ascertained by
using random-digit dialing and Health Care Financing Administration files and
were frequency-matched to cases for age and county of residence. Information on
lifetime leisure-time physical activity was obtained during in-person interviews.
RESULTS: Leisure-time physical activity was significantly associated with reduced
occurrence of ovarian cancer (P =.01). After adjustment for age, parity, oral
contraceptive use, tubal ligation, family history of ovarian cancer, race, and
body mass index, women with the highest level of activity had an odds ratio of
0.73 (95% CI 0.56, 0.94) for ovarian cancer compared with women with the lowest
level of activity. When the relation was analyzed by various recalled time
periods during life, the odds ratios for the highest versus the lowest category
of activity at ages 14-17, 18-21, 22-29, 30-39, 40-49, and >50 years ranged from
0.64-0.78. CONCLUSION: Leisure-time physical activity is associated with reduced
occurrence of epithelial ovarian cancer.
PMID- 11004369
TI - Angiogenesis of endometrial carcinomas assessed by measurement of intratumoral
blood flow, microvessel density, and vascular endothelial growth factor levels.
AB - OBJECTIVE: To evaluate the relationship between blood flow in the tumor assessed
by color Doppler ultrasound, microvessel density, and vascular endothelial growth
factor levels in endometrial carcinoma. METHODS: Forty-nine patients undergoing
surgery for endometrial carcinoma were enrolled. Transvaginal color Doppler
ultrasound was performed preoperatively and the lowest resistance index (RI) in
the tumor was recorded for analysis. Vascular endothelial growth factor in the
tumor was quantified by enzyme immunoassay. The microvessel density of the
excised tumor was assessed immunohistochemically. The relationships between the
corresponding RI, microvessel density, and vascular endothelial growth factor
level of the tumor tissues and clinical and pathologic parameters were analyzed.
RESULTS: Significantly lower RIs were noted in tumors of stage II or greater
(0.37 compared with 0.50, P <.001), of high histologic grade (grade 3) (0.34
compared with 0.49, P =.004), with deep myometrial invasion (one-half depth or
greater) (0.39 compared with 0.49, P =.002), with lymphovascular emboli (0.38
compared with 0.49, P <.001), or with lymph node metastasis (0.30 compared with
0.49, P <.001) compared with stage I tumors and tumors of histologic grade 1 or
2, with superficial myometrial invasion, without lymphovascular emboli, or with
no lymph node metastasis. Increased vascular endothelial growth factor levels and
microvessel density (x200 field) also were detected in tumors of stage II or
greater (975 compared with 129 pg/mg, P =.014; and 88 compared with 61, P =.018,
respectively), with lymphovascular emboli (1138 compared with 120 pg/mg, P =.002;
and 86 compared with 63, P =.023), or with lymph node metastasis (1011 compared
with 95 pg/mg, P <.001; and 98 compared with 61, P =. 019). Resistance index,
microvessel density, and vascular endothelial growth factor levels in the tumor
showed linear correlations (RI compared with microvessel density: r = -.32, P =.
03; RI compared with vascular endothelial growth factor levels: r = -.40, P
=.004; microvessel density compared with vascular endothelial growth factor
levels: r =.36, P =.011). CONCLUSION: Blood flow assessed by color Doppler
ultrasound has histologic and biologic correlations with angiogenesis and
vascular endothelial growth factor levels and might play an important role in
predicting tumor progression and metastasis in endometrial carcinoma.
PMID- 11004370
TI - Differences in perineal lacerations in black and white primiparas.
AB - OBJECTIVE: To test the null hypothesis that there are no differences in incidence
of perineal and vaginal lacerations in primiparous black and white women.
METHODS: We reviewed University of Michigan Hospital delivery records, from July
1996 to December 1998, of black and white women 18 years and older and at least
35 weeks' gestation who had their first vaginal delivery. Birth weight,
episiotomy, gestational age, laceration, length of second stage, oxytocin use,
epidural use, and operative vaginal delivery were analyzed by univariable and
multivariable tests. RESULTS: We analyzed 176 black women (mean age +/- standard
deviation 23.7 +/- 4.7 years; range 18-41 years) and 1633 white women (27.8 +/-
5.4 years; 18-49 years; P <.001). Black women were less likely to have second,
third, or fourth degree lacerations (43% compared with 59%; P <.001). The mean
length of second stage of labor was shorter in the black women (73 +/- 69
minutes; range 3-494 minutes compared with 106 +/- 78 minutes; range 2-642
minutes; P <.001). Infants of black women weighed less (3292 +/- 490 g; 1990-5190
g compared with 3429 +/- 470 g; 1860-4950 g; P <.001). Multivariable analysis
showed that black women were twice as likely to deliver with intact perineums
than white women (P <.001). CONCLUSION: Black primiparas were less likely to
deliver with second-degree or greater lacerations and more likely to deliver with
their perineums intact.
PMID- 11004372
TI - Do we need a subspecialty of female pelvic medicine and reconstructive surgery?
PMID- 11004371
TI - Validity of adolescent and young adult self-report of Papanicolaou smear results.
AB - OBJECTIVE: To assess the validity of adolescent and young adult report of
Papanicolaou smear results and to determine sociodemographic, cognitive, and
behavioral factors associated with incorrect reporting. METHODS: We conducted a
cross-sectional study of 477 female subjects aged 12 to 24 years who attended an
adolescent clinic and had a previous Papanicolaou smear. Subjects completed a
self-administered survey assessing self-report of Papanicolaou smear results,
knowledge about Papanicolaou smears and human papillomavirus (HPV), attitudes
about Papanicolaou screening and follow-up, and risk behaviors. The sensitivity,
specificity, positive predictive value, and negative predictive value of self
reported results were calculated using the cytology report as the standard.
Variables significantly associated with incorrect reporting were entered into
logistic regression models controlling for age and race to determine independent
predictors for incorrect reporting. RESULTS: Of the 477 participants, 128 (27%)
had abnormal cytology reports and 66 (14%) had incorrect self-reports.
Sensitivity of self-report was 0.79, specificity 0.89, positive predictive value
0.72, negative predictive value 0.92, and kappa (kappa) 0.66. The adjusted odds
ratios (OR) and 95% confidence intervals (CI) of the variables comprising a
logistic regression model predicting incorrect reporting were an HPV knowledge
source of zero (OR 2.4, CI 1.0, 5.8), low perceived communication with the
provider (OR 2.1, CI 1.1, 4.0), and no contraception at last intercourse (OR 5.5,
CI 2.7, 11.0). CONCLUSION: The validity of adolescent and young adult self
reported Papanicolaou smear result is high, except among those who lack knowledge
of HPV, perceive poor communication with the provider, and use contraception
inconsistently.
PMID- 11004373
TI - Laparoscopic secondary port conversion using a reusable blunt conical trocar.
AB - BACKGROUND: During operative laparoscopy, large (10 mm or more) ancillary ports
are often used for instrumentation and tissue removal. Although sharp pyramidal
trocars can be used to place these ports, their use appears to increase the risk
of vessel injury and herniation. We describe a simple and cost-effective
technique for converting a 5-mm port to a 10- or 12-mm port using a blunt conical
trocar. TECHNIQUE: When a larger port is required, a previously placed 5-mm port
is removed, and the skin incision is lengthened. A reusable 10- or 12-mm blunt
conical trocar with a threaded sleeve is placed through the incision. The fascial
defect is located by probing and is dilated gently with the blunt tip. Once the
tip is through the fascia, it is advanced through the peritoneal defect with a
clockwise, twisting motion. Afterwards, the fascial defect is closed with a
single, interrupted absorbable suture. EXPERIENCE: We have had no complications
or difficulty when using this technique in 26 cases, either during or after
surgery. CONCLUSION: A reusable blunt conical trocar is a simple, safe, and cost
effective instrument for converting a 5-mm laparoscopic port into a 10- or 12-mm
port.
PMID- 11004375
TI - In this issue
PMID- 11004374
TI - Amniotic fluid volume estimation and the biophysical profile: a confusion of
criteria.
AB - The biophysical profile (BPP) can be used as an initial test of fetal health and
as a secondary back-up assessment of fetuses at risk of adverse outcomes when
preliminary evaluations are not reassuring. The BPP evaluates five
characteristics: fetal movement, tone, breathing, heart reactivity, and amniotic
fluid (AF) volume estimation. Three of the most frequently used obstetric
textbooks define adequate AF volume differently. In two of the three, the stated
method of evaluating AF volume differs from that actually used by the referenced
authors. We reviewed articles by Manning and found that his methodology changed
from a 1-cm pocket in one plane to a 1-cm pocket in two perpendicular planes, and
finally to a 2-cm vertical pocket with a 1-cm horizontal measurement. The 2 x 2
cm pocket is a fourth methodology that has been introduced recently. It is not
known how often and in which groups each of the four methods has been used to
evaluate abnormal AF volumes. The relevance and importance of determining
precisely the ultrasound measurement actually used for investigations are
emphasized by looking at women with AF indices < or = 5. Fifty-three percent of
those women had a 2 x 2 pocket, 72% had a 2 x 1 pocket, and 95% had a 1 x 1
pocket. The diagnosis of low fluid can lead to additional testing, hydration, and
intervention, so the importance of a universal definition linked with pregnancy
outcomes cannot be overemphasized.
PMID- 11004376
TI - Paracelsus and mechanical ventilation.
PMID- 11004377
TI - Automatic and manual mechanical external chest compression devices for
cardiopulmonary resuscitation.
PMID- 11004378
TI - Chronicity of memory impairment in long-term out-of-hospital cardiac arrest
survivors.
AB - As a result of out-of-hospital defibrillation initiatives, many cities have an
increasing population of out-of-hospital cardiac arrest survivors. We previously
identified that one third of these patients suffer memory problems in the months
after resuscitation. The pattern of memory impairment (impaired recall memory and
intact recognition memory) is suggestive of hippocampal damage. In this study we
followed up ten subjects who had previously been found to have memory impairment
after their cardiac arrest. To assess the chronicity of this memory impairment,
we re-tested memory function approximately 3 years after the index events. These
subjects were compared with age and sex matched control subjects with previous
myocardial infarction and no cardiac arrest. Memory was assessed using the
Rivermead Behavioural Memory test (RBMT). To further assess recall and
recognition memory we used the Doors and People test (DPT), which is specifically
designed to identify deficits in these functions. RBMT scores declined
significantly in both groups compared with the original assessment 8 months after
cardiac arrest, possibly an effect of ageing-control group: mean (S.D.) 22.2 (1.
4)-18.4 (2.9); cardiac arrest group: 16.1 (2.7)-14.6 (4.4). The inter-group
difference in RBMT score remained significant (P=0.001). DPT scores were poor in
the cardiac arrest group (mean (S.D.) total 5.8 (2.8)), compared with the control
group (10.8 (3.4)) who scored normally. Both recall and recognition memory were
poor in the cardiac arrest group. We conclude that the memory deficits that we
previously observed in cardiac arrest victims are persistent. Both recall and
recognition memory are affected, implying that non-selective brain injury may be
the mechanism.
PMID- 11004379
TI - Vasopressin pressor effects in critically ill children during evaluation for
brain death and organ recovery.
AB - BACKGROUND: Vasopressin (VP) shows promise as a pressor agent in animals and
adult human cardiac arrest and resuscitation, but has not been studied for
pressor effect in critically ill or arrested children. VP infusion is routine
treatment for diabetes insipidus during brain death evaluation and organ
recovery. We hypothesized that low dose VP infusion during organ recovery in
critically ill children exerts a pressor effect, without major organ toxicity.
METHODS: 34 VP-treated and 29 age-matched critically ill controls (C) < or =18
years were retrospectively reviewed during brain death evaluation and organ
recovery. VP infusion protocol titrated VP dose clinically to urine output, with
high variability. Pressor and inotrope management was titrated clinically to BP,
cerebral perfusion and central venous pressures (when available) and peripheral
perfusion with similar protocol targets for pre-load in VP and C groups. Outcome
measures include dose, type and number of pressors and inotropes. Organ function
was assessed at recovery and 48 h post-transplant by independent surgeon and
transplant program organ function criteria. Analysis by Odds Ratio (OR), and chi
square. RESULTS: VP dose averaged 0.041+/-0.069 U/kg/h. Average baseline mean
arterial pressure (MAP) before VP infusion was 79+/-17 mmHg VP and 76+/-14 mm Hg
C (P=0.6). Subsequent average MAP were: 82+/-21 mmHgVP after VP infusion versus
71+/-16 mmHg C (P=0.01) and 80+/-14 mmHg VP versus 68+/-22 mmHg C (P=0.01).
Ability to wean/stop pressors and inotropes was: dopamine (14/23) 42% VP versus
(10/26) 38% C (P=0.75), dobutamine (4/7) 57% VP versus (0/6) 0% C (P=0.026),
epinephrine (4/5) 80% VP versus (0/6) 0% C (P=0.006),
norepinephrine/phenylephrine (4/4) 100% VP versus (2/5) 40% C (P=0. 057). Alpha
agonist pressor dependence was successfully weaned from 7/9 (78%) VP versus 0/9
(0%) C: odds ratio=7.3, (P<0.01). There was no VP induced dysrhythmia,
hypertension, anuria or toxicity reported. Good organ recovery function was not
significantly different at recovery or 48 h post-transplant for kidney (79% VP
versus 69% C, P=0.068), liver (87% VP versus 95% C, P=0.533), or heart (90% VP
versus 71% C, P=0.11). CONCLUSIONS: Low dose vasopressin infusion exerts a
pressor effect in critically ill children treated for diabetes insipidus during
brain death and organ recovery. VP treated patients were 7.3 times more likely to
wean from alpha agonists than comparably managed age matched controls, without
adverse affect on transplant organ function. We speculate that further
prospective assessment of VP safety and efficacy as a pressor adjunct for
resuscitation of critically ill children is warranted.
PMID- 11004380
TI - Excellent coronary perfusion pressure during cardiopulmonary resuscitation is not
good enough to ensure long-term survival with good neurologic outcome: a porcine
case report.
AB - PURPOSE: To report a case of cerebral ischemia confirmed by magnetic resonance
imaging after successful cardiopulmonary resuscitation (CPR) complicated by acute
respiratory injury. MATERIALS AND METHODS: After 4 min of cardiac arrest,
followed by 3 min of basic life support CPR, a female pig weighing 38 kg received
every 5 min vasopressin (0.4, 0.4 and 0.8 U/kg). After 22 min of cardiac arrest,
including 18 min of CPR, one defibrillation attempt employing 100 J resulted in
return of spontaneous circulation. Neurological evaluation was performed 24 and
96 h after successful CPR. Magnetic resonance imaging was carried out 4 days
after CPR using a clinical 1.5 T scanner. The magnetic resonance imaging protocol
consisted of fast spinecho T2-weighted, as well as spinecho T1-weighted imaging
of the brain. RESULTS: CPR with vasopressin resulted in excellent coronary
perfusion pressure ranging between 35 and 60 mm Hg throughout CPR. Eight minutes
after initiation of chest compressions, bleeding out of the tracheal tube
occurred. This was later confirmed as originating from bilateral bloody pulmonary
infiltrations, resulting in acute respiratory injury in the post-resuscitation
phase. Ninety-six hours after successful CPR, magnetic resonance imaging revealed
bilateral diffuse cerebral vasogenic edema. CONCLUSION: Although excellent
coronary perfusion pressure renders a return of spontaneous circulation more
likely, complications such as acute respiratory injury in the post-resuscitation
phase have to be managed carefully in order to ensure good neurological recovery
from cardiac arrest.
PMID- 11004381
TI - Transthoracic monophasic and biphasic defibrillation in a swine model: a
comparison of efficacy, ST segment changes, and postshock hemodynamics.
AB - OBJECTIVE: Biphasic waveforms for transthoracic defibrillation (DF) have been
tested extensively after brief (15 s) episodes of VF in animal models and in
patients undergoing electrophysiologic testing. The purpose of this study was to
compare the effects mono- and biphasic waveforms for DF on postdefibrillation ST
segments and left ventricular pressure, markers of myocardial injury, after more
extended periods of VF (30 and 90 s). METHODS: 21 anesthetized and instrumented
swine were randomized to truncated exponential monophasic or biphasic waveform
DF. VF was induced electrically and 30 s later, DF with the designated waveform
was attempted with a shock dose of 200 J. If unsuccessful, 300 J and then 360 J
were administered if necessary. Following return to control hemodynamic values
and normalization of the surface ECG, VF was again induced and, after 90 s, DF
was attempted as in the 30 s VF period. CPR was not performed during VF and each
animal was countershocked with only one waveform for both VF episodes. Waveforms
were compared for frequency of first shock defibrillation success, surface ECG
indicators of myocardial injury (ST segment changes at 10, 20, and 30 s after
countershock) and time to return to pre-VF hemodynamics after successful DF, an
indicator of postshock ventricular function. RESULTS: Successful first shock
conversion rates at 30 and 90 s were 60 and 63% for monophasic and 64 and 82% for
biphasic (NS). Biphasic DF after 30 s produced ST segment changes (measured 10 s
after DF) in 1/10 animals while six of eight animals in the monophasic group
showed ST segment changes (P=0.013). After 90 s of VF, ST segment changes were
observed in 6/8 in the monophasic group and 2/10 in the biphasic group (P=0.054).
Differences in the time to hemodynamic recovery (return to control peak left
ventricular pressure) were not observed between biphasic and monophasic waveforms
after 30 or 90 s of VF. CONCLUSIONS: Monophasic and biphasic transthoracic
defibrillation are equally effective in terminating VF of 30 and 90 s duration
and restoring a perfusing rhythm. The biphasic waveform produced less ECG
evidence of transient myocardial injury. However, there was no difference in the
rate of return to control hemodynamics. ST segment changes following countershock
of VF of brief duration are transient and of questionable significance.
PMID- 11004382
TI - Effect of bystander cardiopulmonary resuscitation in out-of-hospital cardiac
arrest patients in Sweden.
AB - BACKGROUND: Information from the Swedish Cardiac Arrest Registry was used to
investigate: (a) The proportion of patients suffering an out-of-hospital cardiac
arrest who were given bystander cardiopulmonary resuscitation (B-CPR). (b) Where
and by whom B-CPR was given. (c) The effect of B-CPR on survival. METHOD: a
prospective, observational study of cardiac arrests reported to the Swedish
Cardiac Arrest Registry. Analyses were based on standardised reports of out-of
hospital cardiac arrests from ambulance organisations in Sweden, serving 60% of
the Swedish population. From 1983 to 1995 approximately 15-20% of the population
had been trained in CPR. RESULTS: Of 9877 patients, collected between January
1990 and May 1995, B-CPR was attempted in 36%. In 56% of these cases, the
bystanders were lay persons and in 25% they were medical personnel. Most of the
arrests took place at home (69%) and only 23% of these patients were given B-CPR
in contrast to cardiac arrest in other places where 53% were given CPR. Survival
to 1 month was significantly higher in all cases that received B-CPR (8.2 vs.
2.5%). The odds ratio for survival to 1 month with B-CPR was in a logistic
regression analysis 2.5 (95% CI 1.9-3.1). CONCLUSIONS: In Sweden, the willingness
and ability to perform B-CPR appears to be relatively widespread. More than half
of B-CPR was performed by laypersons. B-CPR resulted in a two to threefold
increase in survival.
PMID- 11004383
TI - How bystanders perceive their cardiopulmonary resuscitation intervention; a
qualitative study.
AB - The importance of bystander cardiopulmonary resuscitation (CPR) prior to arrival
of the emergency medical service is well documented. In Sweden, CPR is initiated
prior to emergency medical services (EMS) arrival in about 30% of cardiac arrests
out-of-hospital, a figure which should be improved urgently. To do so, it is of
interest to know more about the bystanders' perceptions of their intervention. A
qualitative method inspired by the phenomenographic approach was applied to 19
bystanders who had performed CPR. In the analysis, five main categories and 14
subcategories emerged. The main categories were: to have a sense of humanity, to
have competence, to feel an obligation, to have courage and to feel exposed.
Interviews described how humanity and concern for another human being were the
foundation of their intervention. CPR training offers the possibility to give
appropriate help in this emergency. If the aim of CPR training was extended
beyond teaching the skill of CPR to include preparation of the rescuer for the
intervention and his/her reactions, this might increase the number of people able
to take action in the cardiac arrest situation.
PMID- 11004384
TI - In-hospital resuscitation: association between ACLS training and survival to
discharge.
AB - CONTEXT: No data have been published on the relationship between advanced cardiac
life support (ACLS) training of the individual who initiates resuscitation
efforts and survival to discharge. OBJECTIVE: To determine whether patients whose
arrests were discovered by nurses trained in ACLS had survival rates different
from those discovered by nurses not trained in ACLS. DESIGN: Cohort case
comparison. SETTING: A 550-bed, tertiary care center in central Georgia.
SUBJECTS: Patients whose cardiopulmonary arrest was discovered by a nurse who
activated the in-hospital resuscitation mechanism. MAIN OUTCOME MEASURE: Patient
survival to discharge. RESULTS: Initial rhythm was strongly related to survival
to discharge and individually associated with 57% of the variability in survival.
Nurse's training in advanced cardiac life support was also strongly related to
survival and individually associated with 29% of the variability. Combining both
the variables determined 62% of the variability in survival to discharge.
Patients discovered by an ACLS-trained nurse (n=88) were about four times more
likely to survive (33 survivors, 38%) than were patients, discovered by a nurse
without training in ACLS (n=29, three survivors, 10%). CONCLUSION: Arrest
discovery by nurses trained in ACLS is significantly and dramatically associated
with higher survival-to-discharge rates.
PMID- 11004385
TI - Endobronchial application of high dose epinephrine in out of hospital
cardiopulmonary resuscitation.
PMID- 11004386
TI - A simple model of the thermal prebiotic oligomerization of amino acids.
AB - We construct a probabilistic model with the aid of the Markov chain formalism to
describe and give a physico-chemical justification to an oligomerization process
of a set of amino acids under certain prebiotic conditions. Such chemical process
shows a remarkable bias in the polymer products that our model can explain. Some
predictions and limitations are also discussed.
PMID- 11004387
TI - Complex calcium oscillations and the role of mitochondria and cytosolic proteins.
AB - Intracellular calcium oscillations, which are oscillatory changes of cytosolic
calcium concentration in response to agonist stimulation, are experimentally well
observed in various living cells. Simple calcium oscillations represent the most
common pattern and many mathematical models have been published to describe this
type of oscillation. On the other hand, relatively few theoretical studies have
been proposed to give an explanation of complex intracellular calcium
oscillations, such as bursting and chaos. In this paper, we develop a new
possible mechanism for complex calcium oscillations based on the interplay
between three calcium stores in the cell: the endoplasmic reticulum (ER),
mitochondria and cytosolic proteins. The majority ( approximately 80%) of calcium
released from the ER is first very quickly sequestered by mitochondria.
Afterwards, a much slower release of calcium from the mitochondria serves as the
calcium supply for the intermediate calcium exchanges between the ER and the
cytosolic proteins causing bursting calcium oscillations. Depending on the
permeability of the ER channels and on the kinetic properties of calcium binding
to the cytosolic proteins, different patterns of complex calcium oscillations
appear. With our model, we are able to explain simple calcium oscillations,
bursting and chaos. Chaos is also observed for calcium oscillations in the
bursting mode.
PMID- 11004388
TI - Computing with DNA by operating on plasmids.
AB - A new method of computing using DNA plasmids is introduced and the potential
advantages are listed. The new method is illustrated by reporting a laboratory
computation of an instance of the NP-complete algorithmic problem of computing
the cardinal number of a maximal independent subset of the vertex set of a graph.
A circular DNA plasmid, specifically designed for this method of molecular
computing, was constructed. This computational plasmid contains a specially
inserted series of DNA sequence segments, each of which is bordered by a
characteristic pair of restriction enzyme sites. For the computation reported
here, the DNA sequence segments of this series were used to represent the
vertices of the graph being investigated. By applying a scheme of enzymatic
treatments to the computational plasmids, modified plasmids were generated from
which the solution of the computational problem was selected. This new method of
computing is applicable to a wide variety of algorithmic problems. Further
computations in this style are in progress.
PMID- 11004389
TI - Canalization as a non-genetic source of adaptiveness during morphogenesis:
experimental evidence from analysis of reproductive development in Sorghum
bicolor.
AB - In Sorghum bicolor, perturbations in reproductive development observed following
salt-treatment also influence progeny grown in the absence of NaCl. However, a
developmental reversion of these modifications may be observed throughout two
successive generations. This response, termed canalization, does not
spontaneously occur following growth in the absence of NaCl, but is triggered by
the level of perturbation in parental expression of reproductive characters.
Moreover, canalization is not specific to the perturbed character, but it
includes modifications in reproductive development as a whole. A decrease in
developmental variability coincides with amplitude of the developmental
reversion. This phenomenon is interpreted as an evidence for orientation of the
developmental process towards the lowest free-energy state of the 'epigenetic
landscape'. Involvement of this phenomenon of canalization in developmental
stability, adaptiveness, and evolution is discussed. Moreover, these results
point to the need for a posteriori methods of investigations in order to analyze
self-organized transformations in biological systems.
PMID- 11004390
TI - Probing quantum coherence in a biological system by means of DNA amplification.
AB - As a result of rapid decoherence, quantum effects in biological systems are
usually confined to single electron or hydrogen delocalizations. In principle,
molecular interactions at high temperatures can be guided by quantum coherence if
embedded in a dynamics preventing decoherence. This was experimentally
investigated by analyzing the thermodynamics, kinetics, and quantum mechanics of
the primer/template duplex formation during DNA amplification by polymerase chain
reaction. The structures of the two oligonucleotide primers used for
amplification of a cDNA template were derived either from a repetitive motif or a
fractal distribution of nucleotide residues. Contrary to the computer-based
calculation of the primer melting temperatures (T(m)) that predicted a higher
T(m) for the non-fractal primer due to nearest-neighbor effects, it was found
that the T(m) of the non-fractal primer was actually 2 degrees C lower than that
of its fractal counterpart. A thermodynamic analysis of the amplification
reaction indicated that the primer annealing process followed Bose-Einstein
instead of Boltzmann statistics, with an additional binding potential of mu=500
J/mol or 10(-21) J/molecule due to a superposition of binding states within the
primer/template duplex. The temporal evolution of the Bose-Einstein state was
determined by enzyme kinetic analysis of the association of the primer/template
duplex to Taq polymerase. Assuming that collision with the enzyme interrupted the
superposition, it was found that the Bose-Einstein state lasted for
t(dec)=0.7x10(-12) s, corresponding to the energy dispersion (DeltaE) of quantum
coherent states (mu=DeltaE>/=h/t(dec)). A quantum mechanical analysis revealed
that the coherent state was stabilized by almost vanishing separation energies
between distinct binding states during a temperature-driven shifting of the two
DNA strands in the primer/template duplex. The additional binding potential is
suggested to arise from a short-lived electron tunneling as the result of
overlapping orbitals along the axis of the primer/template duplex. This effect
was unique to the fractal primer due to the number of binding states that
remained almost constant, irrespective of the size of shifting. It is suggested
that fractal structures found in proteins or other macromolecules may facilitate
a short-lived quantum coherent superposition of binding states. This may
stabilize molecular complexes for rapid sorting of correct-from-false binding,
e.g. during folding or association of macromolecules. The experimental model
described in this paper provides a low-cost tool for simulating and probing
quantum coherence in a biological system.
PMID- 11004391
TI - The iron dependent regulatory protein IdeR (DtxR) of Rhodococcus equi.
AB - This paper reports the presence of an ideR gene, which encodes an iron-dependent
regulatory protein, in Rhodococcus erythropolis and in the intracellular pathogen
Rhodococcus equi. The ideR gene of the latter encoded a protein of 230 amino
acids with a molecular mass of 25619. The alpha-helices forming the helix-turn
helix motif of the R. equi protein were identical to those of the DtxR protein of
Corynebacterium diphtheriae, which is an IdeR homologue. This indicates that the
two proteins bind to the same DNA binding site. This was confirmed following
expression of IdeR in Escherichia coli, which showed that the IdeR protein could
repress transcription of the tox promoter of C. diphtheriae in an iron dependent
manner. An open reading frame specifying a 283-amino acid polypeptide similar to
galE encoding UDP-galactose 4-epimerase was present downstream of the ideR gene.
PMID- 11004392
TI - Inducible stx2 phages are lysogenized in the enteroaggregative and other
phenotypic Escherichia coli O86:HNM isolated from patients.
AB - We characterized two Shiga toxin-producing Escherichia coli (STEC) O86:HNM
isolates from a patient with hemolytic uremic syndrome (HUS) or bloody diarrhea.
Both of them did not possess the eaeA gene. However, the isolate from a HUS
patient carried genetic markers of enteroaggregative E. coli (EAEC) and showed
aggregative adherence pattern to HEp-2 cells. The other isolate from bloody
diarrhea, which was negative with EAEC markers, was diffusely adhered to HEp-2
cells. The stx2 gene in both E. coli O86:HNM strains was encoded in each
infectious phage, which was partially homologous to that of strain EDL933, a STEC
O157:H7. These results will help to explain the genotypic divergences of STEC.
PMID- 11004393
TI - The colanic acid gene cluster of Salmonella enterica has a complex history.
AB - The colanic acid gene cluster of Salmonella enterica LT2 was sequenced and
compared with that of Escherichia coli K-12. The two clusters are similar with
divergence slightly higher than average for genes of the two species. The cluster
was divided into four blocks by GC content and seems likely to have transferred
from a higher GC content species to the ancestor of E. coli and S. enterica. All
19 genes of K-12 and 13 genes of LT2 appear to have undergone random genetic
drift with amelioration of the GC content. However, in the case of S. enterica,
we believe that the six genes of the GDP-fucose pathway group were replaced
relatively recently by genes closely related to those of the original donor
species. Two repetitive elements were observed: a bacterial interspersed mosaic
element in the intergenic region between wzx and wcaK in K-12 only and a RSA
(repetitive sequence element) sequence between wcaJ and wzx in LT2 only.
PMID- 11004394
TI - Molecular differentiation of Bifidobacterium species with amplified ribosomal DNA
restriction analysis and alignment of short regions of the ldh gene.
AB - The differentiation of Bifidobacterium species was performed with specific
primers using the PCR technique, the amplified ribosomal DNA restriction analysis
(ARDRA) technique based on reports on the sequence of the 16S rRNA gene and
speciation based on a short region of the ldh gene. Four specific primer sets
were developed for each of the Bifidobacterium species, B. animalis, B. infantis
and B. longum. The use of the ARDRA method made it possible to discriminate
between B. infantis, B. longum and B. animalis with the combination of BamHI,
TaqI and Sau3AI restriction enzymes. The ldh gene sequences of 309-312 bp were
determined for 19 Bifidobacterium strains. Alignment of these short regions of
the ldh gene confirmed that it is possible to distinguish between B. longum and
B. infantis but not between B. lactis and B. animalis.
PMID- 11004395
TI - Effects of tubulin assembly inhibitors on cell division in prokaryotes in vivo.
AB - The bacterial cell division protein FtsZ is a structural analogue of tubulin.
Bacterial mutants in which the ftsZ gene is inactivated are unable to divide.
Numerous inhibitors of tubulin assembly are known, some of which are used as
fungicides. The strong structural homology between FtsZ and tubulin raises the
possibility that some of these inhibitors could affect bacterial cell division.
Here we report that the tubulin assembly inhibitors thiabendazole and 2
methylbenzimidazole cause cell elongation in Escherichia coli and cyanobacteria.
PMID- 11004396
TI - The relationship between glycogen synthesis, biofilm formation and virulence in
salmonella enteritidis.
AB - Salmonella enteritidis accumulated large quantities of intracellular
polysaccharide when grown in unrestricted nutrient conditions. Dense, abundant
cytoplasmic granules were observed by electron microscopy in sections stained by
the periodic acid-chlorite technique, indicating that the polysaccharide was of
the glycogen type. When biofilm-producing S. enteritidis was pre-incubated in
media containing increasing levels of glucose concentration, the levels of both
cytoplasmic glycogen and biofilm rose correlatively to a point where a ceiling
effect was observed. Studies carried out with activators and inhibitors of
glycogen biosynthesis confirmed that biofilm was formed from glycogen cell
stores. On the other hand, the virulence of the biofilm-producing strain in
infected chickens increased proportionally to the amount of stored glycogen,
suggesting a possible role of the glycogen depot in the virulence of S.
enteritidis.
PMID- 11004397
TI - The cloning of a new peroxidase found in lignocellulose cultures of Pleurotus
eryngii and sequence comparison with other fungal peroxidases.
AB - We report cloning and sequencing of gene ps1 encoding a versatile peroxidase
combining catalytic properties of lignin peroxidase (LiP) and manganese
peroxidase (MnP) isolated from lignocellulose cultures of the white-rot fungus
Pleurotus eryngii. The gene contains 15 putative introns, and the deduced amino
acid sequence consists of a 339-residue mature protein with a 31-residue signal
peptide. Several putative response elements were identified in the promoter
region. Amino acid residues involved in oxidation of Mn(2+) and aromatic
substrates by direct electron transfer to heme and long-range electron transfer
from superficial residues as predicted by analogy with Phanerochaete
chrysosporium MnP and LiP, respectively. A dendrogram is presented illustrating
sequence relationships between 29 fungal peroxidases.
PMID- 11004398
TI - Peptide mimics elicit antibody responses against the outer-membrane
lipooligosaccharide of group B neisseria meningitidis.
AB - As an alternative approach towards the development of a meningococcal vaccine,
the potential of peptide mimics of lipooligosaccharide (LOS) to elicit cross
reactive immune responses against LOS was investigated. The heptapeptides SMYGSYN
and APARQLP were identified by enrichment from a coliphage display library with a
LOS-specific monoclonal antibody. Mice immunised with these peptides conjugated
to diphtheria toxoid elicited a total IgG response to LOS with geometric mean
titres 2-4 times higher compared with non-immunised controls. There was an
increase in LOS-specific IgG1 immunoglobulin, whereas specific IgG2a and IgG3
decreased slightly in response to immunisation. The data demonstrated that
peptide mimics can elicit immune responses against meningococcal LOS.
PMID- 11004399
TI - Acetaldehyde metabolism by wine lactic acid bacteria.
AB - Acetaldehyde is a volatile flavor compound present in many fermented foods and is
important in the production of red and white wines. Nine strains of the genera
Lactobacillus and Oenococcus were able to metabolize acetaldehyde in a resting
cell system, whereas two Pediococcus strains were not. Acetic acid and ethanol
were produced from its degradation. A Lactobacillus and an Oenococcus were able
to degrade SO(2)-bound acetaldehyde, as well. A coincubation of resting cells of
Saccharomyces bayanus Premiere Cuvee and Oenococcus oeni Lo111 showed that strain
Lo111 metabolized acetaldehyde produced by the yeast. The ability of malolactic
bacteria to degrade free and SO(2)-bound acetaldehyde has implications for
sensory and color qualities and the use of SO(2) in wine.
PMID- 11004400
TI - The immunosuppressive drug leflunomide affects mating-pheromone response and
sporulation by different mechanisms in Saccharomyces cerevisiae.
AB - Leflunomide (LFM) is a novel anti-inflammatory and immunosuppressive drug, and
inhibits the growth of cytokine-stimulated lymphoid cells in vitro. The effect of
LFM on haploid and diploid cells of Saccharomyces cerevisiae was investigated to
elucidate the molecular mechanism of action of the drug. Using a halo assay, LFM
was shown to enhance the cell cycle arrest of haploid cells induced by mating
pheromone alpha-factor. LFM also inhibited sporulation of diploid cells
completely. S. cerevisiae genes which were cloned to suppress the anti
proliferative effect when present in increased copy number were introduced and
examined for their activity to suppress the effect of LFM. Out of them,
MLF4/SSH4, was found to suppress the sporulation-inhibitory effect of LFM.
However, MLF4 failed to suppress the enhancing effect of LFM on pheromone
response. Thus, LFM is suggested to act on haploid and diploid cells by different
mechanisms.
PMID- 11004401
TI - Elevated zinc induces siderophore biosynthesis genes and a zntA-like gene in
Pseudomonas fluorescens.
AB - Zinc-regulated genes were analyzed in Pseudomonas fluorescens employing
mutagenesis with a reporter gene transposon. Six mutants responded with increased
gene expression to elevated concentrations of zinc. Genetic and biochemical
analysis revealed that in four of the six mutants the transposon had inserted
into genes essential for the biosynthesis of the siderophore pyoverdine. The
growth of one of the mutants was severely impaired in the presence of elevated
concentrations of cadmium and zinc ions. In this mutant, the transposon had
inserted in a gene with high similarity to P-type ATPases involved in zinc and
cadmium ion transport. Four mutants reacted with reduced gene expression to
elevated concentrations of zinc. One of these mutants was sensitive to zinc,
cadmium and copper ions. The genetic region targeted in this mutant did not show
similarity to any known gene.
PMID- 11004402
TI - Survival of free DNA encoding antibiotic resistance from transgenic maize and the
transformation activity of DNA in ovine saliva, ovine rumen fluid and silage
effluent.
AB - To assess the likelihood that the bla gene present in a transgenic maize line may
transfer from plant material to the microflora associated with animal feeds, we
have examined the survival of free DNA in maize silage effluent, ovine rumen
fluid and ovine saliva. Plasmid DNA that had previously been exposed to freshly
sampled ovine saliva was capable of transforming competent Escherichia coli cells
to ampicillin resistance even after 24 h, implying that DNA released from the
diet could provide a source of transforming DNA in the oral cavity of sheep.
Although target DNA sequences could be amplified by polymerase chain reaction
from plasmid DNA after a 30-min incubation in silage effluent and rumen contents,
only short term biological activity, lasting less than 1 min, was observed in
these environments, as shown by transformation to antibiotic resistance. These
experiments were performed under in vitro conditions; therefore further studies
are needed to elucidate the biological significance of free DNA in the rumen and
oral cavities of sheep and in silage effluent.
PMID- 11004403
TI - Purification, characterisation, cloning and sequencing of the gene encoding
oligopeptidase PepO from Streptococcus thermophilus A.
AB - The oligopeptidase PepO from Streptococcus thermophilus A was purified to protein
homogeneity by a five-step chromatography procedure. It was estimated to be a
serine metallopeptidase of 70 kDa, with maximal activity at pH 6.5 and 41 degrees
C. PepO has endopeptidase activity on oligopeptides composed of between five and
30 amino acids. PepO was demonstrated to be active and stable at the pH,
temperature and salt concentrations found in Swiss-type cheese during ripening.
Using a battery of PCR techniques, the pepO gene was amplified, subcloned and
sequenced, revealing an open reading frame of 1893 nucleotides. The amino acid
sequence analysis of the pepO gene-translation product shows homology with PepO
enzymes from other lactic acid bacteria and contains the signature sequence of
the metallopeptidase family.
PMID- 11004404
TI - Cloning of the sth gene from Azotobacter vinelandii and construction of chimeric
soluble pyridine nucleotide transhydrogenases.
AB - The gene encoding the soluble pyridine nucleotide transhydrogenase (STH) of
Azotobacter vinelandii was cloned and sequenced. This is the third sth gene
identified and further defines a new subfamily within the flavoprotein disulfide
oxidoreductases. The three STHs identified all lack one of the redox active
cysteines that are characteristic for this large family of enzymes, and instead
they contain a conserved threonine residue at this position. The recombinant A.
vinelandii enzyme was purified to homogeneity and shown to form filamentous
structures different from those of Pseudomonas fluorescens and Escherichia coli
STH. Chimeric STHs were constructed which showed that the C-terminal region is
important for polymer formation. The A. vinelandii STH containing the C-terminal
region of P. fluorescens or E. coli STH showed structures resembling those of the
STH contributing the C-terminal portion of the protein.
PMID- 11004405
TI - A novel technique for monitoring the development of bacterial biofilms in human
periodontal pockets.
AB - A new technique is presented for analyzing subgingival bacterial plaque.
Different materials (polytetrafluoroethylene, gold, dentin) kept for several days
in periodontal pockets of patients suffering from periodontitis were analyzed by
electron microscopy and fluorescence in situ hybridization (FISH). Those parts of
the carriers extending into the deepest zone of the pockets were predominantly
colonized by spirochetes and Gram-negative bacteria whereas those segments in
contact with a shallower region were colonized by streptococci. Independent of
the material used, the bacterial colonization of the carriers appears to be
similar. FISH using eubacteria- and species-specific oligonucleotides on semi
thin cross-sections of the carriers in combination with confocal laser scanning
microscopy allowed detailed analysis of the architecture of biofilms and
identification of putative periodontal pathogens with single cell resolution.
PMID- 11004406
TI - The alternative sigma factor sigma(28) of the extreme thermophile Aquifex
aeolicus restores motility to an Escherichia coli fliA mutant.
AB - Sigma factor sigma(28) (sigma(F), FliA, SigD) directs RNA polymerase to
transcribe the genes required for flagellar biosynthesis and chemotaxis in many
bacteria, including Bacillus subtilis, Legionella pneumophila, Salmonella
typhimurium, Escherichia coli, Yersinia enterolytica, Treponema maltophilum and
Pseudomonas aeruginosa. Remarkably the fliA gene from the extreme thermophile
Aquifex aeolicus restored motility to the E. coli mutant at relatively low
temperature, albeit partially. This clearly demonstrates that A. aeolicus
sigma(28) is able to direct RNA polymerase to E. coli sigma(28)-dependent
promoters and take part in the complex interactions required to support
transcription of the flagellar apparatus in vivo. The ability of A. aeolicus
sigma(28) to function with mesophilic components shows that critical functional
interactions made by these sigma factors are well conserved, and are not
dependent upon high temperature. We over-produced and purified the sigma(28)
protein and demonstrated binding to E. coli core RNA polymerase in vitro. In
common with SigD from B. subtilis, but unlike most sigma factors, A. aeolicus
sigma(28) showed DNA binding activity in vitro but there was no evidence of
sequence specificity. We note that A. aeolicus sigma(28) is a good candidate for
structural studies.
PMID- 11004407
TI - Membrane vesicles released by Actinobacillus pleuropneumoniae contain proteases
and Apx toxins.
AB - Actinobacillus pleuropneumoniae serotype 1 releases vesicles containing proteases
and Apx toxins into the culture medium. Vesicles were concentrated by
ultracentrifugation and analyzed by electron microscopy and electrophoresis;
their size ranged from 20 to 200 nm. A polyclonal antiserum raised against a
purified high molecular mass secreted protease of serotype 1 recognized this
protease on the surface of the vesicles by immunogold electron microscopy. Higher
molecular mass polypeptides from vesicle extracts were recognized by the
antiserum by Western immunoblot, indicating that the protease could form
oligomers. However, these oligomers were not active against gelatin until
secreted. Additionally, Apx toxins were also present in vesicles, and were
recognized by Western immunoblot by an anti-serotype 1 toxins polyclonal serum.
A. pleuropneumoniae antigens in vesicles were recognized by convalescent-phase
pig sera from animals infected with serotype 1 or 5. The release of vesicles
containing virulence factors could be a tissue damage mechanism in swine
pleuropneumonia.
PMID- 11004408
TI - Identification of novel metabolites in the degradation of phenanthrene by
Sphingomonas sp. strain P2.
AB - Sphingomonas sp. strain P2, which is capable of utilizing phenanthrene as a sole
carbon and energy source, was isolated from petroleum-contaminated soil in
Thailand. Gas chromatography-mass spectrometry and (1)H and (13)C nuclear
magnetic resonance analyses revealed two novel metabolites from the phenanthrene
degradation pathway. One was identified as 5,6-benzocoumarin, which was derived
by dioxygenation at the 1- and 2-positions of phenanthrene, and the other was
determined to be 1,5-dihydroxy-2-naphthoic acid. Other metabolites from
phenanthrene degradation were identified as 7, 8-benzocoumarin, 1-hydroxy-2
naphthoic acid and coumarin. From these results, it is suggested that strain P2
can degrade phenanthrene via dioxygenation at both 1,2- and 3,4-positions
followed by meta-cleavage.
PMID- 11004409
TI - Identification of DNA amplifications near the center of the Streptomyces
coelicolor M145 chromosome.
AB - Linear streptomycete chromosomes frequently undergo spontaneous gross DNA
rearrangements at the terminal regions. Large DNA deletions of the chromosome
ends are in many cases associated with tandemly reiterated DNA amplifications,
found at the border of the deletable areas. In contrast to previous reports, we
have discovered amplifications near the center of the Streptomyces coelicolor
M145 chromosome. The detected amplified units of DNA are 19.9 kb and 16 kb in
length and exist in copy numbers of 30 and 40, respectively. Both amplifications
were located in the same region and share at least 3.6 kb.
PMID- 11004410
TI - Isolation of the dxr gene of Zymomonas mobilis and characterization of the 1
deoxy-D-xylulose 5-phosphate reductoisomerase.
AB - The gene encoding the second enzyme of the 2C-methyl-D-erythritol 4-phosphate
(MEP) pathway for isopentenyl diphosphate biosynthesis, 1-deoxy-D-xylulose 5
phosphate (DXP) reductoisomerase, was cloned and sequenced from Zymomonas
mobilis. The deduced amino acid sequence showed the highest identity (48.2%) to
the DXP reductoisomerase of Escherichia coli. Biochemical characterization of the
purified DXP reductoisomerase showed a strict dependence of the enzyme on NADPH
and divalent cations (Mn(2+), Co(2+) or Mg(2+)). The enzyme is a dimer with a
molecular mass of 39 kDa per subunit and has a specific activity of 19.5 U mg
protein(-1). Catalysis of the intramolecular rearrangement and reduction of DXP
to MEP is competitively inhibited by the antibiotic fosmidomycin with a K(i) of
0.6 microM.
PMID- 11004412
TI - Detection and characterisation of integrons in Salmonella enterica serotype
enteritidis.
AB - Integrons have been widely described among the Enterobacteriaceae including
strains of multi-resistant Salmonella enterica serotype Typhimurium DT104;
however, information with respect to the presence of integrons among S. enterica
serotype Enteritidis strains is limited. Multi-resistant isolates of Enteritidis
were screened for the presence of integrons using a PCR protocol. One integron
was detected in all isolates that were resistant to sulfonamide and streptomycin.
Characterisation of these isolates indicated an integron which ranged in size
between 1000 and 2000 bp and which harboured a gene cassette encoding the ant(3")
Ia gene specifying streptomycin and spectinomycin resistance. Further studies
revealed the integrons to be located on large conjugative plasmids. This appears
to be the first report of plasmid-borne integrons in Enteritidis.
PMID- 11004411
TI - The predicted structure of photopexin from Photorhabdus shows the first
haemopexin-like motif in prokaryotes.
AB - The insect pathogenic bacterium Photorhabdus luminescens secretes several
insecticidal high molecular mass 'toxin complexes'. Analysis of the putative
pathogenicity island surrounding the toxin complex a (tca) locus revealed two
open reading frames (ORFs) of unknown function. The predicted protein sequences
of these ORFs show a repeated motif similar to those found in the vertebrate haem
scavenging molecule haemopexin, limunectin (a phosphocholine binding protein from
Limulus) and the C-terminal domains of matrix metalloproteinases (MMPs) (where
they are thought to be important for cell attachment and adhesion). We have
therefore named the operon photopexin AB and the putative encoded proteins
'photopexins' A and B (PpxA and PpxB). The predicted amino acid sequence of PpxA
was modelled onto the crystal structure of a MMP. Our model predicts not only
that PpxA and PpxB have beta-propeller domains but also that each haemopexin-like
repeat corresponds to one blade of a propeller, suggesting the limunectin
structure itself may also contain two or three such haemopexin-like propellers.
The overall structure of PpxA has striking similarity to that of haemopexin
suggesting that it may be used by the bacterium to scavenge iron containing
compounds from insects. The implications for the potential role of Ppx proteins
in pathogenicity are discussed. This is the first finding of a haemopexin-like
repeat outside plants and animals.
PMID- 11004413
TI - Phagocytosis, oxidative burst, and killing of Candida dubliniensis and Candida
albicans by human neutrophils.
AB - Candida dubliniensis is a phylogenetically closely related species to Candida
albicans. So far virtually nothing is known about the virulence factors of C.
dubliniensis. Cell surface hydrophobicity (CSH) plays a critical role in adhesion
of microorganisms to phagocytic cells; hydrophobic cells of C. albicans have been
reported to be less sensitive to phagocytic killing than hydrophilic cells. C.
dubliniensis displays CSH at 37 degrees C in contrast to C. albicans. To
elucidate this issue, we determined levels of phagocytosis, oxidative burst and
killing by human neutrophils of C. dubliniensis (n=10) compared to C. albicans
(n=10) both cultured at 37 degrees C. Obtained test results revealed no
statistically significant differences between these two yeast species for the
level of phagocytosis (77.3 vs. 76.2% after 60 min), evoked oxidative burst (64.5
vs. 67.3% after 30 min) and killing (72.7 vs. 73.1% after 240 min). Therefore,
human neutrophils can be considered to be equally efficient against these two
yeast species.
PMID- 11004414
TI - Erratum to: "Stimulation of adhesiveness, infectivity, and competitiveness for
nodulation of bradyrhizobium japonicum by its pretreatment with soybean seed
lectin".
PMID- 11004415
TI - Do potential patients prefer tissue plasminogen activator (TPA) over
streptokinase (SK)? An evaluation of the risks and benefits of TPA from the
patient's perspective.
AB - BACKGROUND: In patients with acute myocardial infarction, TPA (compared to SK),
has been shown to reduce the 30-day mortality rate at the expense of an increased
rate of stroke. The assumption in the literature is that were it not for cost
issues, all patients presenting with a myocardial infarction would choose TPA.
Our hypothesis is that, for many informed individuals, regardless of cost, the
increased risk of stroke may deter them from selecting TPA over SK. OBJECTIVE: To
assess which thrombolytic drug informed patients would prefer and to explore the
clinical and economic implications of such preferences. DESIGN: Prospective
survey. SETTING: Tertiary care hospital. PATIENTS: 120 hospitalized patients with
cardiac disease who would be "at risk" for a myocardial infarction.
INTERVENTIONS: Face-to-face interviews utilizing a decision instrument.
MEASUREMENTS: To minimize bias in soliciting patients' preferences and to
standardize the presentation of information we developed a decision instrument
which portrays a case scenario of a myocardial infarction, describes treatment
outcomes (survival and stroke rate), and displays the likelihood of these
outcomes with SK and TPA using three scenarios: a base stroke risk (all patients
data), a lower stroke risk (<75 years old data), a higher stroke risk (>75 years
old data). Outcome data were derived from the published literature (GUSTO study).
RESULTS: When presented the overall results of the GUSTO study, 60/120 (50%)
expressed a preference for SK. When presented the outcome data for the subgroups
of patients <75 years old (lower stroke rate), 37/120 (31%) preferred SK. When
presented the subgroup data for patients >75 years old (higher stroke risk),
67/120 (56%) preferred SK. CONCLUSIONS: Regardless of the scenario that
individuals were presented with, a substantial proportion of individuals (31-56%)
who could potentially require thrombolytic therapy chose SK over TPA. This study
should be repeated in other settings to establish the generalizability of our
results. Assuming that these results will be consistent, considering the
patient's perspective has significant implications on clinical decision making as
well as from an economic perspective.
PMID- 11004416
TI - Which chronic conditions are associated with better or poorer quality of life?
AB - The objective of the present study is to compare the QL of a wide range of
chronic disease patients. Secondary analysis of eight existing data sets,
including over 15,000 patients, was performed. The studies were conducted between
1993 and 1996 and included population-based samples, referred samples,
consecutive samples, and/or consecutive samples. The SF-36 or SF-24 were employed
as generic QL instruments. Patients who were older, female, had a low level of
education, were not living with a partner, and had at least one comorbid
condition, in general, reported the poorest level of QL. On the basis of rank
ordering across the QL dimensions, three broad categories could be distinguished.
Urogenital conditions, hearing impairments, psychiatric disorders, and
dermatologic conditions were found to result in relatively favorable functioning.
A group of disease clusters assuming an intermediate position encompassed
cardiovascular conditions, cancer, endocrinologic conditions, visual impairments,
and chronic respiratory diseases. Gastrointestinal conditions,
cerebrovascular/neurologic conditions, renal diseases, and musculoskeletal
conditions led to the most adverse sequelae. This categorization reflects the
combined result of the diseases and comorbid conditions. If these results are
replicated and validated in future studies, they can be considered in addition to
information on the prevalence of the diseases, potential benefits of care, and
current disease-specific expenditures. This combined information will help to
better plan and allocate resources for research, training, and health care.
PMID- 11004417
TI - Measuring quality of sedation in adult mechanically ventilated critically ill
patients. the Vancouver Interaction and Calmness Scale. Sedation Focus Group.
AB - There are no reliable, valid, and responsive scales to measure the quality of
sedation in adult critically ill patients. Our objective was to develop a
summated rating scale with these properties and to define the minimal clinically
important difference (MCID). We developed and tested the scale in an 18-bed
medical-surgical intensive care unit (ICU) (12-bed acute and 6-bed subacute
unit). Following identification of relevant domains and item derivation, 116
observations were made on 38 patients; psychometric properties and interrater
reliability were assessed to allow item reduction. The final scale consisted of
two five-item subscales quantifying calmness and interaction along a continuum
from 5 to 30 points. Interrater reliability was 0.89 and 0.90; internal
consistency was 0. 95 for both subscales. To test construct validity, MCID, and
responsiveness 302 observations were made on 54 patients. Construct validity:
calmness score vs. need for further intervention to make the patient calm (R =
0.82, P < 0.001); interaction score discriminated between acute vs. subacute
units, mean scores 15.28 +/- 8.26 vs. 23.54 +/- 7.42, mean difference 8.27 (95%
CI - 10.32 to -6.22); MCID - 2.2 and 2.5 for the calmness and interaction
subscales; Guyatt's responsiveness statistics - 1.4 and 2.3. The Vancouver
Interaction and Calmness Scale (VICS) is reliable, valid, and responsive.
PMID- 11004418
TI - Construction of the Patient-Oriented Prostate Utility Scale (PORPUS): a
multiattribute health state classification system for prostate cancer.
AB - Health status indexes, such as the EuroQol, consist of a health state
classification system and a set of utility weights. Indexes measure quality of
life using a 0-1 utility score. Utilities for outcomes in prostate cancer (PC)
are of unique importance, but generic indexes do not represent PC outcomes (e.g.,
sexual, urinary, bowel dysfunction) well, and may not capture their full impact.
As a step toward improved utility measurement, we constructed a classification
system for PC. We generated items for each of six health domains and rated their
importance using interviews with 10 clinical experts and 80 patients. Key
concepts were selected for each domain using item importance weightings, and a
set of predetermined criteria. Text was developed to express levels of severity
within each domain. Experts and two additional groups of patients (n = 40, n =
96) evaluated textual clarity and endorsed the content validity of the
instrument. The final system consists of 10 domains with 4-6 levels each. The
content validity of the system was endorsed by patients and experts. In
conjunction with a set of utility weights, it may be used to develop a health
status index, to improve utility measurement in patients, and to serve as a short
psychometric (nonutility) instrument.
PMID- 11004419
TI - Choice of effect measure for epidemiological data.
AB - The debate concerning the choice of effect measure for epidemiologic data has
been renewed in the literature, and it suggests some continuing disagreement
between the pertinent clinical and statistical criteria. In this article, some
defining characteristics of the main choices of effect measure [risk difference
(RD), relative risk (RR), and odds ratio (OR)] for binary data are presented and
compared, with consideration of both the clinical and statistical perspectives.
Relationships of these measures to the relative risk reduction (RRR) and number
needed to treat (NNT) are also discussed. A numerical comparison of models of
constant RD, RR, and OR is made to assess when and by how much they might differ
in practice. Typically the models show only small numerical differences, unless
extreme extrapolation is involved. The RD and RR models can predict impossible
event rates, either less than zero or greater than 100%. Each measure has
potential theoretical justification. RD and RR may enjoy some advantages for
communication of risk, but OR may be preferred for data analysis. A clear
distinction should be maintained between the objectives of data analysis and
subsequent risk communication, and different effect measures may be needed for
each.
PMID- 11004420
TI - Comparison of ultrasound, radiography, and clinical examination in the diagnosis
of acute maxillary sinusitis: a systematic review.
AB - The objective of this study was to assess the discriminative properties of the
methods for diagnosing acute maxillary sinusitis (AMS) in unselected patients.
The study design was a systematic review of evaluation studies identified by
using Medline, by searching reference lists, by hand searches, and by contacting
investigators. Evaluation studies were conducted anywhere in the world. Subjects
were adults with suspected AMS. Main outcome measures were: sensitivity,
specificity, positive and negative likelihood ratios of the primary studies,
weighted means of these parameters in each comparison (clinical examination,
radiography, and ultrasound compared to a reference standard in diagnosing AMS),
and summary ROC curves and their Q* points where sensitivity equals specificity.
For the years from 1962 to present, 49 study reports were found; 11 articles on
studies that included a total of 1144 patients were eligible. Compared to sinus
puncture, radiography was the most accurate method for diagnosing AMS: the Q*
point on the summary ROC curve was 0.82 (95% confidence interval, CI, 0.78-0.85).
Ultrasound was slightly less accurate than radiography compared to sinus puncture
(Q* 0.80, 95% CI 0.76-0.83). Only two articles reported clinical examination
compared to sinus puncture and the Q* for them was 0.75 (95% 0.58-0.86). Clinical
examination is a rather unreliable method for diagnosing AMS, even in the hands
of experienced specialists. Using radiography or ultrasound improves the accuracy
of diagnosis. The diagnosis of AMS is rarely studied in primary care settings.
Future comparative trials should preferably combine diagnosis and treatment,
evaluating the two aspects of clinical management as unit.
PMID- 11004421
TI - Are clinical practice guidelines valid for primary care?
AB - Development of evidence-based clinical practice guidelines has emphasized
treatment efficacy under methodologically rigorous conditions; internal validity
(i.e., efficacy) has been assessed well. Despite their experimental foundations,
guidelines originally were considered physician education tools relevant to
singular, idealized encounters. Now, in rushing to generalize, quantify, and
regulate quality, guidelines are being applied to whole populations as quality
review criteria. Clinical guidelines do not make operational how, or even make
clear whether they should be so used. We studied the external validity, the
generalizability and measurability for primary care, of a guideline for treatment
of systolic heart failure. Patient and clinical factors reducing generalizability
were examined. Imprecise definition and reliance on single measures of
recommendations were studied as limits to measurability. Patient, physician,
organizational, and system factors influenced guideline validity. Attention to
myriad invalidity sources undermining implementation and evaluation of efforts to
improve quality and outcomes of primary care is critical.
PMID- 11004422
TI - Education, aging, and health: to what extent can the rise in educational level
relieve the future health (care) burden associated with population aging in the
Netherlands?
AB - This article describes to what extent the expected rise in the educational level
of the Dutch population can counterbalance the increases in the prevalence of ill
health and health care utilization based on the aging of the population for the
period 1996-2020. Logistic regression models are used to estimate current
differences in health (care utilization) by age, sex, and educational level,
using data from the Netherlands Health Interview Survey. The current differences
in health (care utilization) are applied to national projections of the
composition of the population by age, sex, and educational level. Also, scenarios
have been made in which the health differences by educational level are assumed
to converge and diverge. The rise in the educational level counteracts the
expected increases in ill-health based on population aging to a substantial
degree (10-100%). We therefore recommend that in projections of ill-health also
changes in educational level are taken into account.
PMID- 11004423
TI - What contributions do languages other than English make on the results of meta
analyses?
AB - Including only a portion of all available evidence may introduce systematic
errors into the meta-analytic process and threaten its validity. We set out to
examine whether language restricted meta-analyses, compared to language inclusive
meta-analyses, provide different estimates of the effectiveness of interventions
evaluated in randomized trials. We identified and retrieved all 79 meta-analyses
from several disease areas in which explicit eligibility criteria regarding trial
selection were reported. General characteristics and quality of reporting of the
meta-analyses were assessed using a validated instrument. We explored the effects
of language of publication of the randomized trials on the quantitative results
using logistic regression analyses. Language restricted meta-analyses, compared
to language inclusive meta-analyses, did not differ with respect to the estimate
of benefit of the effectiveness of an intervention (ROR = 0.98; 95% CI: 0.81
1.17). These results were also robust after a series of sensitivity analyses.
This study provides no evidence that language restricted meta-analyses lead to
biased estimates of intervention effectiveness. We encourage others to replicate
this study using different sampling frames, clinical topics and interventions.
PMID- 11004424
TI - New insights into metabolic and vascular management of type 2 diabetes.
Proceedings of a meeting. Brussels, Belgium, September 1999.
PMID- 11004425
TI - Therapeutic objectives and their practical achievement in type 2 diabetes.
AB - This paper offers a broad but selective account of the context of type 2 diabetes
at the start of the new millennium. It outlines the major long-term threats to
health and life of people with type 2 diabetes and indicates that, while their
relative impacts may differ, the burden of the specific "microvascular" and the
atherosclerotic "macrovascular" complications of diabetes weigh as heavily on
people with type 2 as on those with type 1 diabetes. Correction of hyperglycemia
still has a leading role among therapeutic objectives in type 2 diabetes, but the
concept of the "defence in depth" and the crucial importance of control of
arterial pressure and correction of dyslipidemia - the "bad companions" in
diabetes - is stressed. Other defences against tissue and organ failure in
diabetes are described, highlighting the importance of regular, systematic
screening for risk factors and early manifestations of tissue damage. Broader
organizational, social and economic factors in diabetes care are touched upon and
the need for strong alliances of all concerned parties - care providers,
managers, health politicians, and above all informed and motivated people with
diabetes themselves - is underlined with reference to the World Health
Organization/International Diabetes Federation St. Vincent Declaration Initiative
in Europe and its recent 10-year anniversary "Istanbul Commitment" to full
implementation of the Declaration.
PMID- 11004426
TI - Diamicron MR once daily is effective and well tolerated in type 2 diabetes: a
double-blind, randomized, multinational study.
AB - In a double-blind, multicenter, multinational study, the long-term efficacy and
safety of Diamicron(R)MR, a new gliclazide formulation taken once daily at lower
dose (30-120 mg/day) was compared with Diamicron(R) (80-320 mg/day) taken twice
daily in type 2 diabetic outpatients. After a 2-week run-in period, 800 patients
with poor blood glucose control were randomized to Diamicron(R)MR (n=401) or
Diamicron(R) (n=399). After a 4-month titration period, the efficacy and safety
of Diamicron(R)MR was compared with Diamicron(R) over a 6-month fixed-dose
treatment period. The ability to switch from Diamicron(R) to Diamicron(R)MR was
then assessed during an additional 2-month follow-up period. Equivalence between
treatment with Diamicron(R)MR and Diamicron(R) was compared by a non-inferiority
test; the limit of equivalence was set at 0.5% for HbA(1c) and 1 mmol/l for
fasting plasma glucose (FPG). The treatment groups were comparable at baseline.
After 10 months of treatment, Diamicron(R)MR was as efficient as Diamicron(R) in
controlling blood glucose, with a mean end point difference in HbA(1c) of -0.08
(0. 08)%, significantly lower than the equivalence limit (p<0.001). Similar
results were obtained for FPG.The safety of Diamicron(R)MR and Diamicron(R) was
equally high. The incidence of hypoglycemia was particularly low (0.2
hypoglycemia/100 patient months) in the elderly population, which represented
almost 40% of the included patients. This study demonstrates that 30 to 120 mg of
Diamicron(R)MR taken once daily is at least as efficient as 80 to 320 mg of
Diamicron(R) taken in divided doses with respect to HbA(1c) and FPG levels, with
a similar safety profile.
PMID- 11004427
TI - Tissue-specific effects of sulfonylureas: lessons from studies of cloned K(ATP)
channels.
AB - Sulfonylureas stimulate insulin secretion in type-2 diabetic patients by blocking
ATP-sensitive (K(ATP)) potassium channels in the pancreatic beta-cell membrane.
This effect is mediated by the binding of the drug to the sulfonylurea receptor
(SUR) subunit of the channel. K(ATP) channels are also present in other tissues,
but often contain different types of SUR subunits (e.g., SUR1 in beta-cells,
SUR2A in heart, SUR2B in smooth muscle). The sensitivity of these different types
of K(ATP) channels to sulfonylureas is variable: gliclazide and tolbutamide block
the beta-cell, but not the cardiac or smooth muscle, types of K(ATP) channel. In
contrast, glibenclamide blocks all three types of channel with similar affinity.
The reversibility of the drugs also varies, with tolbutamide and gliclazide being
reversible on all three types of K(ATP) channel, while glibenclamide is
reversible on cardiac, but not beta-cell, K(ATP) channels. This review summarizes
current knowledge of how sulfonylureas act on the different types of K(ATP)
channel found in beta-cells and in extrapancreatic tissues, and discusses the
implications of these findings for their use as therapeutic agents.
PMID- 11004428
TI - Possible pathophysiological mechanisms for diabetic angiopathy in type 2
diabetes.
AB - The expression of large and small vessel disease in type 2 diabetes differs from
that observed in type 1, with a higher prevalence of atherosclerosis and
hypertension, maculopathy rather than proliferative retinopathy, and nephropathy
of a more complex nature. Such differences are mirrored by differences in
vascular pathophysiology with an early impairment of microvascular vasodilatory
reserve being a prominent feature. The defect appears to be endothelium dependent
and in conjunction with evidence of endothelium activation suggests that the
endothelium plays a crucial role in the pathogenesis of vascular disease in type
2 diabetes and may even be an intrinsic feature or common antecedent of the
insulin resistance syndrome. Several cellular mechanisms may be proposed linking
insulin resistance and endothelial dysfunction including (i) abnormalities of
common signal transduction mechanisms, (ii) alterations in cell membrane fluidity
altering the expression and/or presentation of a wide range of receptors, or
(iii) changes in oxidative stress. It is intuitively unlikely that the alteration
of a single signal transduction mechanism could be a common cause, particularly
as aspects of endothelial dysfunction implicate different mechanisms.
Accordingly, changes in oxidative stress, either stemming from glucose-mediated
increased free-radical generation and/or reduction of antioxidant capacity, are
strong contender mechanisms. Not only may increased oxidative stress result in
the quenching of nitric oxide, neutralizing its many protective functions, but it
may also damage DNA, protein structure, and membrane properties. Elucidating the
links between oxidative stress, endothelial function, and insulin resistance has
important implications for the prevention of diabetic angiopathy and perhaps for
the prevention of diabetes itself.
PMID- 11004429
TI - In vitro and in vivo antioxidant properties of gliclazide.
AB - Diabetes is a state of increased oxidant stress and there is evidence that
oxidation may play a role in the genesis of complications. Gliclazide, a
sulfonylurea hypoglycemic drug, has been shown to possess free radical scavenging
properties. This study examined the effects of in vitro supplementation with
gliclazide and other sulfonylureas as on low-density lipoprotein (LDL) oxidation
and the total plasma antioxidant capacity (TPAC). In a separate study, the
effects of 10 months of oral gliclazide therapy on oxidative parameters were
assessed in 44 type 2 diabetic patients. Gliclazide, but not glibenclamide,
glimepiride, glipizide or tolbutamide, inhibited LDL oxidation and enhanced TPAC.
With the addition of 1 microM gliclazide, oxidation lag time increased from
53.6+/-2.6 to 113.6+/-5.1 min (p<0.001), and TPAC increased from 1. 09+/-0.11 to
1.23+/-0.11 mM (p<0.01). Administration of either modified release or standard
gliclazide to type 2 diabetic patients resulted in a fall in 8-isoprostanes, a
marker of lipid oxidation, and an increase in the antioxidant parameters TPAC,
SOD and thiols. These studies show that gliclazide possesses antioxidant
properties that produce measurable clinical effects at therapeutic doses.
PMID- 11004430
TI - Correction of glycosylated oxyhemoglobin-induced impairment of endothelium
dependent vasodilatation by gliclazide.
AB - We have investigated whether gliclazide, a second-generation sulfonylurea
hypoglycemic agent, interferes with the impairment of endothelium-dependent
nitric-oxide-mediated relaxation produced by 14%-glycosylated human oxyhemoglobin
(GHHb). For comparative purposes, other agents, like glibenclamide,
aminoguanidine, ascorbic acid or superoxide dismutase (SOD), were also tested.
GHHb (10 nM) caused a reduction in endothelium-dependent relaxation induced by
acetylcholine (1 nM to 10 microM) in both isolated aortic segments and mesenteric
microvessels from normoglycemic nondiabetic rats. Preincubation of the vessels
with gliclazide (100 nM to 10 microM) prevented the impairment of endothelial
relaxation, the threshold concentration of gliclazide being 300 nM. In addition,
10 microM gliclazide also prevented the reduction by 10 nM GHHb of the relaxation
induced by exogenous nitric oxide (NO, 10 nM to 100 microM). Determination of
superoxide anion release measured by the reduction in ferricytochrome c indicated
that GHHb produced significant amounts of these free radicals that were
concentration-dependently inhibited by gliclazide. The impairment of endothelium
mediated responses was also prevented by 100 U/ml SOD or 10 microM ascorbic acid,
but not by 10 microM glibenclamide or 100 microM aminoguanidine. We conclude that
gliclazide can reduce the impairment of nitric-oxide-mediated endothelium
dependent relaxation produced by GHHb. This reduction is likely related to the
antioxidant properties of the drug, a mechanism suggested by these studies which
demonstrate the inactivation of superoxide anions produced by the glycosylated
protein by gliclazide.
PMID- 11004431
TI - Effect of gliclazide on monocyte-endothelium interactions in diabetes.
AB - Enhanced monocyte-endothelial cell interactions have been documented in diabetes.
Because adherence of monocytes to the endothelium is one of the earliest events
in the development of atherosclerosis, its alteration may represent one of the
mechanisms leading to accelerated atherosclerosis in diabetic patients. Previous
studies have suggested that lipoprotein oxidation and protein glycation may
contribute to the increased monocyte binding to the diabetic vasculature. Based
on the recent finding that gliclazide has free-radical scavenging activity, we
examined the ex vivo and in vitro effects of this drug on human monocyte binding
to endothelial cells. Our results demonstrate that short-term administration of
gliclazide to patients with type 2 diabetes lowers the enhanced adhesion of
diabetic monocytes observed before gliclazide treatment (163+/-24% over control
values, p<0.005) to levels similar to those observed in controls. They also show
that gliclazide (10 microg/ml) reduces in vitro by approximately 35% both
oxidized low-density lipoprotein (LDL)- and glycated albumin-induced monocyte
adhesion to endothelial cells. Based on these results, we next investigated the
molecular mechanisms responsible for the inhibitory effect of gliclazide on
glycated albumin-induced monocyte adhesion to endothelium. In glycated albumin
treated endothelial cells, we observed induction of cell-associated expression of
E-selectin (ELAM-1; 170+/-10% over control values, p<0.005), intercellular cell
adhesion molecule-1 (ICAM-1; 131+/-8% over control values, p<0.005) and vascular
cell adhesion molecule-1 (VCAM-1; 134+/-8% over control values, p<0.005),
augmentation in the levels of the transcripts of these molecules, and an increase
in the DNA binding of NF-kappaB in the promoters of these antigens. Gliclazide
markedly inhibited the induction of all these parameters. Because the oxidative
stress-sensitive transcription factor NF-kappaB is implicated in endothelial cell
activation, the observed inhibitory effect of gliclazide on NF-kappaB activation
and glycated albumin-induced expression of DNA binding activity for the NF-kappaB
site in the ELAM-1, ICAM-1 and VCAM-1 promoters seems to be due to its
antioxidant properties. These results suggest that gliclazide, by its ability to
reduce endothelial activation, may exert potential beneficial effects in the
prevention of atherosclerosis associated with type 2 diabetes.
PMID- 11004432
TI - Prevention of endothelial dysfunction in streptozotocin-induced diabetic rats by
gliclazide treatment.
AB - The aim of the present work was to analyze whether the oral hypoglycemic drug
gliclazide affects diabetic endothelial dysfunction in streptozotocin-induced
diabetic rats. Gliclazide was compared with glibenclamide, ascorbic acid, and
aminoguanidine. An insulin-dependent model of diabetes was selected to exclude
insulin-releasing effects of the drugs. Both in isolated aortic segments and
mesenteric microvessels, endothelium-dependent relaxation evoked by acetylcholine
(ACh, 1 nM to 10 microM) was significantly reduced in vessels from diabetic
animals. This impairment was reversed when the segments were previously incubated
with 100 U/ml superoxide dismutase. When streptozotocin-induced diabetic rats
were orally treated from the time of diabetes induction with gliclazide (10
mg/kg) or ascorbic acid (250 mg/kg), ACh-induced endothelium-dependent relaxation
was well preserved both in aortic segments and mesenteric microvessels. In
addition, the impaired vasodilatation to exogenous nitric oxide (NO) in aortic
segments was also improved in gliclazide-treated diabetic rats. On the other
hand, oral treatment with glibenclamide (1 and 10 mg/kg) or aminoguanidine (250
mg/kg) did not produce significant improvements in diabetic endothelial
dysfunction. We conclude that gliclazide reverses the endothelial dysfunction
associated with diabetes. This effect appears to be due not to the metabolic
actions of the drug but rather to its antioxidant properties, as it can be
mimicked by other antioxidants. We propose that the mechanism involved is the
inactivation of reactive oxygen species, which are increased in diabetes probably
as a result of increased early protein glycosylation products, such as
glycosylated hemoglobin (HbA(1c)). These effects of gliclazide are not shared by
other oral hypoglycemic agent such as glibenclamide, or by blockade of advanced
glycosylation end product (AGE) generation with aminoguanidine.
PMID- 11004433
TI - Excitation energy transfer from phycobilisomes to photosystems: a phenomenon
associated with the temporal separation of photosynthesis and nitrogen fixation
in a cyanobacterium, Plectonema boryanum(1).
AB - Plectonema boryanum shows temporal separation of photosynthesis and nitrogen
fixation under diazotrophic conditions. Low temperature fluorescence studies have
shown that in vivo the nitrogen fixing and photosynthesizing cells are adapted to
'state 2' and 'state 1', respectively. During nitrogen fixation phycobilisomes
seem to transfer excitation energy to photosystem I whereas during oxygenic
photosynthesis the energy is transferred to photosystem II. The state 2 adapted N
phase cells failed to undergo transition to state 1 while P-phase cells exhibited
state 1 to state 2 transition. The nitrogen fixing cells showed a decreased level
of psbC transcript, lack of CP47 in thylakoid membrane, and presence of the F685
peak but absence of the F695 peak in 77 K fluorescence spectra. These results
suggest that the metabolic and molecular changes associated with nitrogen
fixation may favor direct energy transfer from the phycobilisomes to photosystem
I. This should help the organism to achieve low photosystem II and high
photosystem I activity to set temporal separation of nitrogen fixation and
photosynthesis for photoautotrophic growth under diazotrophic conditions.
PMID- 11004434
TI - Conformational relaxation following reduction of the photoactive
bacteriopheophytin in reaction centers from Blastochloris viridis. Influence of
mutations at position M208.
AB - The photochemically trapped bacteriopheophytin (BPh) b radical anion in the
active branch (Phi(A)(&z.rad;-)) of reaction centers (RCs) from Blastochloris
(formerly called Rhodopseudomonas) viridis is characterized by 1H-ENDOR as well
as optical absorption spectroscopy. The two site-directed mutants YF(M208) and
YL(M208), in which tyrosine at position M208 is replaced by phenylalanine and
leucine, respectively, are investigated and compared with the wild type. The
residue at M208 is in close proximity to the primary electron donor, P, the
monomeric bacteriochlorophyll (BChl), B(A), and the BPh, Phi(A), that are
involved in the transmembrane electron transfer to the quinone, Q(A), in the RC.
The analysis of the ENDOR spectra of Phi(A)(&z.rad;-) at 160 K indicates that two
distinct states of Phi(A)(&z.rad;-) are present in the wild type and the mutant
YF(M208). Based on a comparison with Phi(A)(&z.rad;-) in RCs of Rhodobacter
sphaeroides the two states are interpreted as torsional isomers of the 3-acetyl
group of Phi(A). Only one Phi(A)(&z.rad;-) state occurs in the mutant YL(M208).
This effect of the leucine residue at position M208 is explained by steric
hindrance that locks the acetyl group in one specific position. On the basis of
these results, an interpretation of the optical absorption difference spectrum of
the state Phi(A)(&z.rad;-)Q(A)(&z.rad;-) is attempted. This state can be
accumulated at 100 K and undergoes an irreversible change between 100 and 200 K
[Tiede et al., Biochim. Biophys. Acta 892 (1987) 294-302]. The corresponding
absorbance changes in the BChl Q(x) and Q(y) regions observed in the wild type
also occur in the YF(M208) mutant but not in YL(M208). The observed changes in
the wild type and YF(M208) are assigned to RCs in which the 3-acetyl group of
Phi(A) changes its orientation. It is concluded that this distinct structural
relaxation of Phi(A) can significantly affect the optical properties of B(A) and
contribute to the light-induced absorption difference spectra.
PMID- 11004435
TI - Covalent modification of the catalytic sites of the H(+)-ATPase from chloroplasts
with 2-nitreno-ADP. Modification of the catalytic site 1 (tight) and catalytic
sites 1 and 2 together impairs both uni-site and multi-site catalysis of ATP
synthesis and ATP hydrolysis.
AB - After isolation and purification, the H(+)-ATPase from chloroplasts, CF(0)F(1),
contains one endogenous ADP at a catalytic site, and two endogenous ATP at non
catalytic sites. Incubation with 2-azido-[alpha-(32)P]ADP leads to tight binding
of azido-nucleotides. Free nucleotides were removed by three consecutive passages
through centrifugation columns, and upon UV-irradiation most of the label was
covalently bound. The labelled enzyme was digested by trypsin, the peptides were
separated by ion exchange chromatography into nitreno-AMP, nitreno-ADP and
nitreno-ATP labelled peptides, and these were then separated by reversed phase
chromatography. Amino acid sequence analysis was used to identify the type of the
nucleotide binding site. After incubation with 2-azido-[alpha-(32)P]ADP, the
covalently bound label was found exclusively at beta-Tyr-362. Incubation
conditions with 2-azido-[alpha-(32)P]ADP were varied, and conditions were found
which allow selective binding of the label to different catalytic sites,
designated as 1, 2 and 3 in order of decreasing affinity for ADP, and either
catalytic site 1 or catalytic sites 1 and 2 together were labelled. For
measurements of the degree of inhibition by covalent modification, CF(0)F(1) was
reconstituted into phosphatidylcholine liposomes, and the membranes were
energised by an acid-base transition in the presence of a K(+)/valinomycin
diffusion potential. The rate of ATP synthesis was 50-80 s(-1), and the rate of
ATP hydrolysis was 15 s(-1) measured under multi-site conditions. Covalent
modification of either catalytic site 1 or catalytic sites 1 and 2 together
inhibited ATP synthesis and ATP hydrolysis equally, the degree of inhibition
being proportional to the degree of modification. Extrapolation to complete
inhibition indicates that derivatisation of catalytic site 1 leads to complete
inhibition when 1 mol 2-nitreno-ADP is bound per mol CF(0)F(1). Derivatisation of
catalytic sites 1 and 2 together extrapolates to complete inhibition when 2 mol 2
nitreno-ADP are bound per CF(0)F(1). The rate of ATP synthesis and the rate of
ATP hydrolysis were measured as a function of the substrate concentration from
multi-site to uni-site conditions with derivatised CF(0)F(1) and with non
derivatised CF(0)F(1). ATP synthesis and ATP hydrolysis under uni-site and under
multi-site condition were inhibited by covalent modification of either catalytic
site 1 or catalytic sites 1 and 2 together. The results indicate that
derivatisation of site 1 inhibits activation of the enzyme and that cooperative
interactions occur at least between the catalytic sites 2 and 3.
PMID- 11004436
TI - Revealing the structure of the photosystem II chlorophyll binding proteins, CP43
and CP47.
AB - A review of the structural properties of the photosystem II chlorophyll binding
proteins, CP47 and CP43, is given and a model of the transmembrane helical
domains of CP47 has been constructed. The model is based on (i) the amino acid
sequence of the spinach protein, (ii) an 8 A three-dimensional electron density
map derived from electron crystallography and (iii) the structural homology which
the membrane spanning region of CP47 shares with the six N-terminal transmembrane
helices of the PsaA/PsaB proteins of photosystem I. Particular emphasis has been
placed on the position of chlorophyll molecules assigned in the 8 A three
dimensional map of CP47 (K.-H. Rhee, E.P. Morris, J. Barber, W. Kuhlbrandt,
Nature 396 (1998) 283-286) relative to histidine residues located in the
transmembrane regions of this protein which are likely to form axial ligands for
chlorophyll binding. Of the 14 densities assigned to chlorophyll, the model
predicted that five have their magnesium ions within 4 A of the imidazole
nitrogens of histidine residues. For the remaining seven histidine residues the
densities attributed to chlorophylls were within 4-8 A of the imidazole nitrogens
and thus too far apart for direct ligation with the magnesium ion within the
tetrapyrrole head group. Improved structural resolution and reconsiderations of
the orientation of the porphyrin rings will allow further refinement of the
model.
PMID- 11004437
TI - Solution structure of the NADP(H)-binding component (dIII) of proton
translocating transhydrogenase from Rhodospirillum rubrum.
AB - Transhydrogenase is a proton pump found in the membranes of bacteria and animal
mitochondria. The solution structure of the expressed, 21.5 kDa, NADP(H)-binding
component (dIII) of transhydrogenase from Rhodospirillum rubrum has been solved
by NMR methods. This is the first description of the structure of dIII from a
bacterial source. The protein adopts a Rossmann fold: an open, twisted, parallel
beta-sheet, flanked by helices. However, the binding of NADP(+) to dIII is
profoundly different to that seen in other Rossmann structures, in that its
orientation is reversed: the adenosine moiety interacts with the first
betaalphabetaalphabeta motif, and the nicotinamide with the second. Features in
the structure that might be responsible for changes in nucleotide-binding
affinity during catalysis, and for interaction with other components of the
enzyme, are identified. The results are compared with the recently determined,
high-resolution crystal structures of human and bovine dIII which also show the
reversed nucleotide orientation.
PMID- 11004438
TI - Application of the obligate aerobic yeast Yarrowia lipolytica as a eucaryotic
model to analyse Leigh syndrome mutations in the complex I core subunits PSST and
TYKY.
AB - We have used the obligate aerobic yeast Yarrowia lipolytica to reconstruct and
analyse three missense mutations in the nuclear coded subunits homologous to
bovine TYKY and PSST of mitochondrial complex I (proton translocating
NADH:ubiquinone oxidoreductase) that have been shown to cause Leigh syndrome (MIM
25600), a severe progressive neurodegenerative disorder. While homozygosity for a
V122M substitution in NDUFS7 (PSST) has been found in two siblings with
neuropathologically proven Leigh syndrome (R. Triepels et al., Ann. Neurol. 45
(1999) 787), heterozygosity for a P79L and a R102H substitution in NDUFS8 (TYKY)
has been found in another patient (J. Loeffen et al., Am. J. Hum. Genet. 63
(1998) 1598). Mitochondrial membranes from Y. lipolytica strains carrying any of
the three point mutations exhibited similar complex I defects, with V(max) being
reduced by about 50%. This suggests that complex I mutations that clinically
present as Leigh syndrome may share common characteristics. In addition changes
in the K(m) for n-decyl-ubiquinone and I(50) for hydrophobic complex I inhibitors
were observed, which provides further evidence that not only the hydrophobic,
mitochondrially coded subunits, but also some of the nuclear coded subunits of
complex I are involved in its reaction with ubiquinone.
PMID- 11004439
TI - Nitric oxide reductases in bacteria.
AB - Nitric oxide reductases (NORs) that are found in bacteria belong to the large
enzyme family which includes cytochrome oxidases. Two types of bacterial NORs
have been characterised. One is a cytochrome bc-type complex (cNOR) that receives
electrons from soluble redox protein donors, whereas the other type (qNOR) lacks
the cytochrome c component and uses quinol as the electron donor. The latter
enzyme is present in several pathogens that are not denitrifiers. We summarise
the current knowledge on bacterial NORs, and discuss the evolutionary
relationship between them and cytochrome oxidases in this review.
PMID- 11004440
TI - Diversity and origin of alternative NADH:ubiquinone oxidoreductases.
AB - Mitochondria from various organisms, especially plants, fungi and many bacteria
contain so-called alternative NADH:ubiquinone oxidoreductases that catalyse the
same redox reaction as respiratory chain complex I, but do not contribute to the
generation of transmembrane proton gradients. In eucaryotes, these enzymes are
associated with the mitochondrial inner membrane, with their NADH reaction site
facing either the mitochondrial matrix (internal alternative NADH:ubiquinone
oxidoreductases) or the cytoplasm (external alternative NADH:ubiquinone
oxidoreductases). Some of these enzymes also accept NADPH as substrate, some
require calcium for activity. In the past few years, the characterisation of
several alternative NADH:ubiquinone oxidoreductases on the DNA and on the protein
level, of substrate specificities, mitochondrial import and targeting to the
mitochondrial inner membrane has greatly improved our understanding of these
enzymes. The present review will, with an emphasis on yeast model systems,
illuminate various aspects of the biochemistry of alternative NADH:ubiquinone
oxidoreductases, address recent developments and discuss some of the questions
still open in the field.
PMID- 11004441
TI - The transmembrane domain and the proton channel in proton-pumping
transhydrogenases.
AB - Proton-pumping nicotinamide nucleotide transhydrogenases are composed of three
main domains, the NAD(H)-binding and NADP(H)-binding hydrophilic domains I (dI)
and III (dIII), respectively, and the hydrophobic domain II (dII) containing the
assumed proton channel. dII in the Escherichia coli enzyme has recently been
characterised with regard to topology and a packing model of the helix bundle in
dII is proposed. Extensive mutagenesis of conserved charged residues of this
domain showed that important residues are betaHis91 and betaAsn222. The pH
dependence of betaH91D, as well as betaH91C (unpublished), when compared to that
of wild type shows that reduction of 3-acetylpyridine-NAD(+) by NADPH, i.e., the
reverse reaction, is optimal at a pH essentially coinciding with the pK(a) of the
residue in the beta91 position. It is therefore concluded that the wild-type
transhydrogenase is regulated by the degree of protonation of betaHis91. The
mechanisms of the interactions between dI+dIII and dII are suggested to involve
pronounced conformational changes in a 'hinge' region around betaR265.
PMID- 11004442
TI - Mitochondrial electron transfer in the wheat pathogenic fungus Septoria tritici:
on the role of alternative respiratory enzymes in fungicide resistance.
AB - Certain phytopathogenic fungi are able to express alternative NADH- and quinol
oxidising enzymes that are insensitive to inhibitors of the mitochondrial
respiratory Complexes I and III. To assess the extent to which such enzymes
confer tolerance to respiration-targeted fungicides, an understanding of
mitochondrial electron transfer in these species is required. An isolation
procedure has been developed which results in intact, active and coupled
mitochondria from the wheat pathogen Septoria tritici, as evidenced by
morphological and kinetic data. Exogenous NADH, succinate and malate/glutamate
are readily oxidised, the latter activity being only partly (approx. 70%)
sensitive to rotenone. Of particular importance was the finding that azoxystrobin
(a strobilurin fungicide) potently inhibits fungal respiration at the level of
Complex III. In some S. tritici strains investigated, a small but significant
part of the respiratory activity (approx. 10%) is insensitive to antimycin A and
azoxystrobin. Such resistant activity is sensitive to octyl gallate, a specific
inhibitor of the plant alternative oxidase. This enzyme, however, could not be
detected immunologically. On the basis of the above findings, a conceptual
mitochondrial electron transfer chain is presented. Data are discussed in terms
of developmental and environmental regulation of the composition of this chain.
PMID- 11004443
TI - Characterization of the complex I-associated ubisemiquinone species: toward the
understanding of their functional roles in the electron/proton transfer reaction.
AB - NADH-ubiquinone oxidoreductase (called complex I for mitochondrial enzyme and NDH
1 for bacterial counterparts) is an energy transducer, which utilizes the redox
energy derived from the oxidation of NADH with ubiquinone to generate an
electrochemical proton gradient (Deltamu(H(+))) across the membrane. The complex
I/NDH-1 contain one non-covalently bound flavin mononucleotide and as many as
eight iron-sulfur clusters as electron transfer components in common. In
addition, electron paramagnetic resonance (EPR) spectroscopic studies have
revealed that three ubisemiquinone (SQ) species with distinct spectroscopic and
thermodynamic properties are detectable in complex I and function as
electron/proton translocators. Thus, the understanding of molecular properties of
the individual quinone species is prerequisite to elucidate the energy-coupling
mechanism of complex I. We have investigated these SQ species using EPR
spectroscopy and found that the three SQ species have strikingly different
properties. We will report characteristics of these SQ species and discuss
possible functional roles of individual quinone species in the electron/proton
transfer reaction of complex I/NDH-1.
PMID- 11004444
TI - Characterization of two novel redox groups in the respiratory NADH:ubiquinone
oxidoreductase (complex I).
AB - The proton-pumping NADH:ubiquinone oxidoreductase is the first of the respiratory
chain complexes in many bacteria and mitochondria of most eukaryotes. The
bacterial complex consists of 14 different subunits. Seven peripheral subunits
bear all known redox groups of complex I, namely one FMN and five EPR-detectable
iron-sulfur (FeS) clusters. The remaining seven subunits are hydrophobic proteins
predicted to fold into 54 alpha-helices across the membrane. Little is known
about their function, but they are most likely involved in proton translocation.
The mitochondrial complex contains in addition to the homologues of these 14
subunits at least 29 additional proteins that do not directly participate in
electron transfer and proton translocation. A novel redox group has been detected
in the Neurospora crassa complex, in an amphipathic fragment of the Escherichia
coli complex I and in a related hydrogenase and ferredoxin by means of UV/Vis
spectroscopy. This group is made up by the two tetranuclear FeS clusters located
on NuoI (the bovine TYKY) which have not been detected by EPR spectroscopy yet.
Furthermore, we present evidence for the existence of a novel redox group located
in the membrane arm of the complex. Partly reduced complex I equilibrated to a
redox potential of -150 mV gives a UV/Vis redox difference spectrum that cannot
be attributed to the known cofactors. Electrochemical titration of this
absorption reveals a midpoint potential of -80 mV. This group is believed to
transfer electrons from the high potential FeS cluster to ubiquinone.
PMID- 11004445
TI - Catalysis in fumarate reductase.
AB - In the absence of oxygen many bacteria are able to utilise fumarate as a terminal
oxidant for respiration. In most known organisms the fumarate reductases are
membrane-bound iron-sulfur flavoproteins but Shewanella species produce a
soluble, periplasmic flavocytochrome c(3) that catalyses this reaction. The
active sites of all fumarate reductases are clearly conserved at the structural
level, indicating a common mechanism. The structures of fumarate reductases from
two Shewanella species have been determined. Fumarate, succinate and a partially
hydrated fumarate ligand are found in equivalent locations in different crystals,
tightly bound in the active site and close to N5 of the FAD cofactor, allowing
identification of amino acid residues that are involved in substrate binding and
catalysis. Conversion of fumarate to succinate requires hydride transfer from FAD
and protonation by an active site acid. The identity of the proton donor has been
open to question but we have used structural considerations to suggest that this
function is provided by an arginine side chain. We have confirmed this
experimentally by analysing the effects of site-directed mutations on enzyme
activity. Substitutions of Arg402 lead to a dramatic loss of activity whereas
neither of the two active site histidine residues is required for catalysis.
PMID- 11004446
TI - Haem-polypeptide interactions during cytochrome c maturation.
AB - Cytochrome c maturation involves the translocation of a polypeptide, the
apocytochrome, and its cofactor, haem, through a membrane, before the two
molecules are ligated covalently. This review article focuses on the current
knowledge on the journey of haem during this process, which is known best in the
Gram-negative bacterium Escherichia coli. As haem always occurs bound to protein,
its passage across the cytoplasmic membrane and incorporation into the
apocytochrome appears to be mediated by a set of proteinaceous maturation
factors, the Ccm (cytochrome c maturation) proteins. At least three of them,
CcmC, CcmE and CcmF, are thought to interact directly with haem. CcmE binds haem
covalently, thus representing an intermediate of the haem trafficking pathway.
CcmC is required for binding of haem to CcmE, and CcmF for releasing it from CcmE
and transferring it onto the apocytochrome. The mechanism by which haem crosses
the cytoplasmic membrane is currently unknown.
PMID- 11004447
TI - A novel protein transport system involved in the biogenesis of bacterial electron
transfer chains.
AB - The Tat system is a recently discovered bacterial protein transport pathway that
functions primarily in the biosynthesis of proteins containing redox active
cofactors. Analogous transport systems are found in plant organelles. Remarkably
and uniquely the Tat system functions to transported a diverse range of folded
proteins across a biological membrane, a feat that must be achieved without
rendering the membrane freely permeable to protons and other ions. Here we review
the operation of the bacterial Tat system and propose a model for the structural
organisation of the Tat preprotein translocase.
PMID- 11004448
TI - What fuels polypeptide translocation? An energetical view on mitochondrial
protein sorting.
AB - Protein sorting into mitochondria is achieved by the concerted action of at least
four translocation complexes. Vectorial transport of polypeptide chains by these
complexes requires different driving forces. In particular, Deltapsi, matrix
adenosine triphosphate and the free energy of the binding to other protein
components are used in series to achieve sorting of proteins to the various
mitochondrial subcompartments. The processes providing the translocation energy
are presented in this review and their impact for protein sorting into and within
mitochondria is discussed.
PMID- 11004449
TI - Crystallographic studies of the conformational changes that drive directional
transmembrane ion movement in bacteriorhodopsin.
AB - Recent advances in the determination of the X-ray crystallographic structures of
bacteriorhodopsin, and some of its photointermediates, reveal the nature of the
linkage between the relaxation of electrostatic and steric conflicts at the
retinal and events elsewhere in the protein. The transport cycle can be now
understood in terms of specific and well-described displacements of hydrogen
bonded water, and main-chain and side-chain atoms, that lower the pK(a)s of the
proton release group in the extracellular region and Asp-96 in the cytoplasmic
region. Thus, local electrostatic conflict of the photoisomerized retinal with
Asp-85 and Asp-212 causes deprotonation of the Schiff base, and results in a
cascade of events culminating in proton release to the extracellular surface.
Local steric conflict of the 13-methyl group with Trp-182 causes, in turn, a
cascade of movements in the cytoplasmic region, and results in reprotonation of
the Schiff base. Although numerous questions concerning the mechanism of each of
these proton (or perhaps hydroxyl ion) transfers remain, the structural results
provide a detailed molecular explanation for how the directionality of the ion
transfers is determined by the configurational relaxation of the retinal.
PMID- 11004450
TI - Electron transfer during the oxidation of ammonia by the chemolithotrophic
bacterium Nitrosomonas europaea.
AB - The combined action of ammonia monooxygenase, AMO, (NH(3)+2e(-)+O(2)-->NH(2)OH)
and hydroxylamine oxidoreductase, HAO, (NH(2)OH+H(2)O-->HNO(2)+4e(-)+4H(+))
accounts for ammonia oxidation in Nitrosomonas europaea. Pathways for electrons
from HAO to O(2), nitrite, NO, H(2)O(2) or AMO are reviewed and some recent
advances described. The membrane cytochrome c(M)552 is proposed to participate in
the path between HAO and ubiquinone. A bc(1) complex is shown to mediate between
ubiquinol and the terminal oxidase and is shown to be downstream of HAO. A novel,
red, low-potential, periplasmic copper protein, nitrosocyanin, is introduced.
Possible mechanisms for the inhibition of ammonia oxidation in cells by
protonophores are summarized. Genes for nitrite- and NO-reductase but not N(2)O
or nitrate reductase are present in the genome of Nitrosomonas. Nitrite reductase
is not repressed by growth on O(2); the flux of nitrite reduction is controlled
at the substrate level.
PMID- 11004451
TI - Mammalian mitochondrial inner membrane cationic and neutral amino acid carriers.
PMID- 11004452
TI - Identification and functions of new transporters in yeast mitochondria.
AB - The genome of Saccharomyces cerevisiae encodes 35 putative members of the
mitochondrial carrier family. Known members of this family transport substrates
and products across the inner membranes of mitochondria. We are attempting to
identify the functions of the yeast mitochondrial transporters via high-yield
expression in Escherichia coli and/or S. cerevisiae, purification and
reconstitution of their protein products into liposomes, where their transport
properties are investigated. With this strategy, we have already identified the
functions of seven S. cerevisiae gene products, whose structural and functional
properties assigned them to the mitochondrial carrier family. The functional
information obtained in the reconstituted system and the use of knock-out yeast
strains can be usefully exploited for the investigation of the physiological role
of individual transporters. Furthermore, the yeast carrier sequences can be used
to identify the orthologous proteins in other organisms, including man.
PMID- 11004453
TI - Biogenesis of iron-sulfur proteins in eukaryotes: a novel task of mitochondria
that is inherited from bacteria.
AB - Fe/S clusters are co-factors of numerous proteins with important functions in
metabolism, electron transport and regulation of gene expression. Presumably,
Fe/S proteins have occurred early in evolution and are present in cells of
virtually all species. Biosynthesis of these proteins is a complex process
involving numerous components. In mitochondria, this process is accomplished by
the so-called ISC (iron-sulfur cluster assembly) machinery which is derived from
the bacterial ancestor of the organelles and is conserved from lower to higher
eukaryotes. The mitochondrial ISC machinery is responsible for biogenesis iron
sulfur proteins both within and outside the organelle. Maturation of the latter
proteins involves the ABC transporter Atm1p which presumably exports iron-sulfur
clusters from the organelle. This review summarizes recent developments in our
understanding of the biogenesis of iron-sulfur proteins both within bacteria and
eukaryotes.
PMID- 11004454
TI - How do uncoupling proteins uncouple?
AB - According to the proton buffering model, introduced by Klingenberg, UCP1 conducts
protons through a hydrophilic pathway lined with fatty acid head groups that
buffer the protons as they move across the membrane. According to the fatty acid
protonophore model, introduced by Garlid, UCPs do not conduct protons at all.
Rather, like all members of this gene family, they are anion carriers. A variety
of anions are transported, but the physiological substrates are fatty acid (FA)
anions. Because the carboxylate head group is translocated by UCP, and because
the protonated FA rapidly diffuses across the membrane, this mechanism permits FA
to behave as regulated cycling protonophores. Favoring the latter mechanism is
the fact that the head group of long-chain alkylsulfonates, strong acid analogues
of FA, is also translocated by UCP.
PMID- 11004455
TI - Effects of nitric oxide and peroxynitrite on the cytochrome oxidase K(m) for
oxygen: implications for mitochondrial pathology.
AB - This review summarises current knowledge about the effect of oxygen on cytochrome
oxidase activity in vitro and in vivo. Cytochrome oxidase normally operates above
its K(m) for oxygen in vivo. However, decreases in the intracellular oxygen
concentration (hypoxia) under physiological extremes, or during pathophysiology,
can cause mitochondrial respiration to become oxygen limited. Inhibitors that
raise the enzyme's K(m) will induce oxygen limitation under apparently normoxic
conditions. It is known that the concentrations of nitric oxide and peroxynitrite
are raised in a number of pathophysiological conditions. These compounds are
capable of reversibly and irreversibly raising the cytochrome oxidase K(m) for
oxygen. Therefore, measurements of cell and mitochondrial respiration in vitro
that fail to systematically vary oxygen through the range of physiological
concentrations are likely to underestimate the effects of nitric oxide and
peroxynitrite in vivo.
PMID- 11004456
TI - Mitochondrial bioenergetics in aging.
AB - Mitochondria are strongly involved in the production of reactive oxygen species,
considered as the pathogenic agent of many diseases and of aging. The
mitochondrial theory of aging considers somatic mutations of mitochondrial DNA
induced by oxygen radicals as the primary cause of energy decline;
experimentally, complex I appears to be mostly affected and to become strongly
rate limiting for electron transfer. Mitochondrial bioenergetics is also deranged
in human platelets upon aging, as shown by the decreased Pasteur effect
(enhancement of lactate production by respiratory chain inhibition). Cells
counteract oxidative stress by antioxidants; among lipophilic antioxidants,
coenzyme Q is the only one of endogenous biosynthesis. Exogenous coenzyme Q,
however, protects cells from oxidative stress by conversion into its reduced
antioxidant form by cellular reductases.
PMID- 11004457
TI - Reversal of nitric oxide-, peroxynitrite- and S-nitrosothiol-induced inhibition
of mitochondrial respiration or complex I activity by light and thiols.
AB - Nitric oxide (NO) and its derivatives peroxynitrite and S-nitrosothiols inhibit
mitochondrial respiration by various means, but the mechanisms and/or the
reversibility of such inhibitions are not clear. We find that the NO-induced
inhibition of respiration in isolated mitochondria due to inhibition of
cytochrome oxidase is acutely reversible by light. Light also acutely reversed
the inhibition of respiration within iNOS-expressing macrophages, and this
reversal was partly due to light-induced breakdown of NO, and partly due to
reversal of the NO-induced inhibition of cytochrome oxidase. NO did not cause
inhibition of complex I activity within isolated mitochondria, but 0.34 mM
peroxynitrite, 1 mM S-nitroso-N-acetylpenicillamine or 1 mM S-nitrosoglutathione
did cause substantial inhibition of complex I activity. Inhibition by these
reagents was reversed by light, dithiothreitol or glutathione-ethyl ester, either
partially or completely, depending on the reagent used. The rapid inhibition of
complex I activity by S-nitroso-N-acetylpenicillamine also occurred in conditions
where there was little or no release of free NO, suggesting that the inhibition
was due to transnitrosylation of the complex. These findings have implications
for the physiological and pathological regulation of respiration by NO and its
derivatives.
PMID- 11004458
TI - Re-emerging structures: continuing crystallography of the bacterial reaction
centre.
AB - The reaction centre is nature's solar battery, and is found in a number of
variations on a common theme in plants, algae and photosynthetic bacteria. During
the last 20 years, a combination of X-ray crystallography, spectroscopy and
mutagenesis has provided increasingly detailed insights into the mechanism of
light energy transduction in the bacterial reaction centre. This mini-review
looks at the application of X-ray crystallography to the bacterial reaction
centre, focussing in particular on recent information on the structural
consequences of site-directed mutagenesis, the roles played by water molecules in
the reaction centre, the mechanism of ubiquinone reduction, and studies of the
phospholipid environment of the protein.
PMID- 11004459
TI - Succinate: quinone oxidoreductases: new insights from X-ray crystal structures.
AB - Membrane-bound succinate dehydrogenases (succinate:quinone reductases, SQR) and
fumarate reductases (quinol:fumarate reductases, QFR) couple the oxidation of
succinate to fumarate to the reduction of quinone to quinol and also catalyse the
reverse reaction. SQR (respiratory complex II) is involved in aerobic metabolism
as part of the citric acid cycle and of the aerobic respiratory chain. QFR is
involved in anaerobic respiration with fumarate as the terminal electron
acceptor, and is part of an electron transport chain catalysing the oxidation of
various donor substrates by fumarate. QFR and SQR complexes are collectively
referred to as succinate:quinone oxidoreductases (EC 1.3.5.1), have very similar
compositions and are predicted to share similar structures. The complexes consist
of two hydrophilic and one or two hydrophobic, membrane-integrated subunits. The
larger hydrophilic subunit A carries covalently bound flavin adenine dinucleotide
and subunit B contains three iron-sulphur centres. QFR of Wolinella succinogenes
and SQR of Bacillus subtilis contain only one hydrophobic subunit (C) with two
haem b groups. In contrast, SQR and QFR of Escherichia coli contain two
hydrophobic subunits (C and D) which bind either one (SQR) or no haem b group
(QFR). The structure of W. succinogenes QFR has been determined at 2.2 A
resolution by X-ray crystallography (C.R.D. Lancaster, A. Kroger, M. Auer, H.
Michel, Nature 402 (1999) 377-385). Based on this structure of the three protein
subunits and the arrangement of the six prosthetic groups, a pathway of electron
transfer from the quinol-oxidising dihaem cytochrome b to the site of fumarate
reduction and a mechanism of fumarate reduction was proposed. The W. succinogenes
QFR structure is different from that of the haem-less QFR of E. coli, described
at 3.3 A resolution (T.M. Iverson, C. Luna-Chavez, G. Cecchini, D.C. Rees,
Science 284 (1999) 1961-1966), mainly with respect to the structure of the
membrane-embedded subunits and the relative orientations of soluble and membrane
embedded subunits. Also, similarities and differences between QFR transmembrane
helix IV and transmembrane helix F of bacteriorhodopsin and their implications
are discussed.
PMID- 11004460
TI - The mitochondrial cyanide-resistant oxidase: structural conservation amid
regulatory diversity.
AB - Mitochondria from all plants, many fungi and some protozoa contain a cyanide
resistant, alternative oxidase that functions in parallel with cytochrome c
oxidase as the terminal oxidase on the electron transfer chain. Characterization
of the structural and potential regulatory features of the alternative oxidase
has advanced considerably in recent years. The active site is proposed to contain
a di-iron center belonging to the ribonucleotide reductase R2 family and modeling
of a four-helix bundle to accommodate this active site within the C-terminal two
thirds of the protein has been carried out. The structural features of this
active site are conserved among all known alternative oxidases. The post
translational regulatory features of the alternative oxidase are more variable
among organisms. The plant oxidase is dimeric and can be stimulated by either
alpha-keto acids or succinate, depending upon the presence or absence,
respectively, of a critical cysteine residue found in a conserved block of amino
acids in the N-terminal region of the plant protein. The fungal and protozoan
alternative oxidases generally exist as monomers and are not subject to organic
acid stimulation but can be stimulated by purine nucleotides. The origins of
these diverse regulatory features remain unknown but are correlated with sequence
differences in the N-terminal third of the protein.
PMID- 11004461
TI - Crystallographic location of two Zn(2+)-binding sites in the avian cytochrome
bc(1) complex.
AB - The chicken mitochondrial ubiquinol cytochrome c oxidoreductase (bc(1) complex)
is inhibited by Zn(2+) ions, but with higher K(i) ( approximately 3 microM) than
the corresponding bovine enzyme. When equilibrated with mother liquor containing
200 microM ZnCl(2) for 7 days, the crystalline chicken bc(1) complex specifically
binds Zn(2+) at 4 sites representing two sites on each monomer in the dimer.
These two sites are close to the stigmatellin-binding site, taken to be center
Q(o) of the Q-cycle mechanism, and are candidates for the inhibitory site. One
binding site is actually in the hydrophobic channel between the Q(o) site and the
bulk lipid phase, and may interfere with quinone binding. The other is in a
hydrophilic area between cytochromes b and c(1), and might interfere with the
egress of protons from the Q(o) site to the intermembrane aqueous medium. No zinc
was bound near the putative proteolytic active site of subunits 1 and 2
(homologous to mitochondrial processing peptidase) under these conditions.
PMID- 11004462
TI - Fusion protein approach to improve the crystal quality of cytochrome bo(3)
ubiquinol oxidase from Escherichia coli.
AB - Crystals of cytochrome bo(3) ubiquinol oxidase from E. coli diffract X-rays to
3.5 A and the structure determination is in progress. The limiting factor to the
elucidation of the structural detail is the quality of the crystals; the
diffraction spots from the crystals are diffused which leads to difficulties in
processing the data beyond 4.0 A. Weak protein-protein contacts within the
crystal lattice is assumed to be the cause of this problem. To improve these
contacts, we have introduced protein Z to the C-terminal end of the subunit IV of
cytochrome bo(3) and expressed both proteins as a single fusion. We have
successfully obtained crystals of this fusion protein. The spot shape problem has
clearly been solved in the crystals of the fusion protein although further
optimization is necessary to obtain higher resolution. We also discuss the
potential applications of this approach to the crystallization of membrane
proteins in general.
PMID- 11004463
TI - Proton-coupled electron transfer at the Q(o) site: what type of mechanism can
account for the high activation barrier?
AB - In Rhodobacter sphaeroides, transfer of the first electron in quinol oxidation by
the bc(1) complex shows kinetic features (a slow rate (approx. 1.5 x 10(3)/s),
high activation energy (approx. 65 kJ/mol) and reorganization energy, lambda (2.5
V)) that are unexpected from Marcus theory and the distances shown by the
structures. Reduction of the oxidized iron-sulfur protein occurs after formation
of the enzyme-substrate complex, and involves a H-transfer in which the electron
transfer occurs through the approx. 7 A of a bridging histidine forming a H-bond
with quinol and a ligand to 2Fe-2S. The anomalous kinetic features can be
explained by a mechanism in which the electron transfer is constrained by coupled
transfer of the proton. We discuss this in the context of mutant strains with
modified E(m,7) and pK for the iron-sulfur protein, and Marcus theory for proton
coupled electron transfer. We suggest that transfer of the second proton and
electron involve movement of semiquinone in the Q(o) site, and rotation of the
Glu of the conserved -PEWY- sequence. Mutational studies show a key role for the
domain proximal to heme b(L). The effects of mutation at Tyr-302 (Tyr-279 in
bovine sequence) point to a possible linkage between conformational changes in
the proximal domain, and changes leading to closure of the iron-sulfur protein
access channel at the distal domain.
PMID- 11004464
TI - The cytochrome b(6)f complex: structural studies and comparison with the bc(1)
complex.
AB - Electron crystallography of the chloroplastic b(6)f complex allowed the
calculation of projection maps of crystals negatively stained or embedded in
glucose. This gives insights into the overall structure of the extra- and
transmembrane domains of the complex. A comparison with the structure of the
bc(1) complex, the mitochondrial homologue of the b(6)f complex, suggests that
the transmembrane domains of the two complexes are very similar, confirming the
structural homology deduced from sequence analysis. On the other hand, the
extramembrane organisation of the c-type cytochrome and of the Rieske protein
seems quite different. Nevertheless, the same type of movement of the Rieske
protein is observed in the b(6)f as in the bc(1) complex upon the binding of the
quinol analogue stigmatellin. Crystallographic data also suggest movements in the
transmembrane domains of the b(6)f complex, which would be specific of the b(6)f
complex.
PMID- 11004465
TI - Protonation reactions in relation to the coupling mechanism of bovine cytochrome
c oxidase.
AB - Identification of the locations of protonatable sites in cytochrome c oxidase
that are influenced by reactions in the binuclear centre is critical to
assessment of proposed coupling mechanisms, and to controversies on where the
pumping steps occur. One such protonation site is that which governs
interconversion of the isoelectronic 607 nm 'P(M)' and 580 nm 'F' forms of the
two-electron-reduced oxygen intermediate. Low pH favours protonation of a site
that is close to an electron paramagnetic resonance (EPR)-silent radical species
in P(M), and this induces a partial electronic redistribution to form an EPR
detectable tryptophan radical in F. A further protonatable group that must be
close to the binuclear centre has been detected in bacterial oxidases by Fourier
transform infrared spectroscopy from pH-dependent changes in the haem-bound CO
vibration frequency at low temperatures. However, in bovine cytochrome c oxidase
under similar conditions of measurement, haem-bound CO remains predominantly in a
single 1963 cm(-1) form between pH 6.5 and 8.5, indicating that this group is not
present. Lack of pH dependence extends to the protein region of the CO photolysis
spectra and suggests that both the reduced and the reduced/CO states do not have
titratable groups that affect the binuclear centre strongly in the pH range 6.5
8.5. This includes the conserved glutamic acid residue E242 whose pK appears to
be above 8.5 even in the fully oxidised enzyme. The results are discussed in
relation to recent ideas on coupling mechanism.
PMID- 11004466
TI - Towards understanding the chemistry of photosynthetic oxygen evolution: dynamic
structural changes, redox states and substrate water binding of the Mn cluster in
photosystem II.
AB - This mini-review summarizes my postdoctoral research in the labs of T.
Wydrzynski/C.B. Osmond, J.H.A. Nugent/M.C.W. Evans and V.K. Yachandra/K.
Sauer/M.P. Klein. The results are reported in the context of selected data from
the literature. Special emphasis is given to the mode of substrate water binding,
Mn oxidation states and the structures of the Mn cluster in the four (meta)stable
redox states of the oxygen evolving complex. The paper concludes with a working
model for the mechanism of photosynthetic water oxidation that combines mu-oxo
bridge oxidation in the S(3) state (V.K. Yachandra, K. Sauer, M.P. Klein, Chem.
Rev. 96 (1996) 2927-2950) with O-O bond formation between two terminal Mn-hydroxo
ligands during the S(3)-->(S(4))-->S(0) transition.
PMID- 11004467
TI - Cloning and expression of cDNAs encoding plant V-ATPase subunits in the
corresponding yeast null mutants.
AB - Complementation of yeast null mutants is widely used for cloning of homologous
genes from heterologous sources. We have used this method to clone the relevant V
ATPase genes from lemon fruit and Arabidopsis thaliana cDNA libraries. The pH
levels are very different in the vacuoles of the lemon fruit and the A. thaliana,
yet both are the result of the activity of the same enzyme complex, namely the V
ATPase. In order to investigate the mechanism that enables the enzyme to maintain
such differences in pH values, we have compared the subunit composition of the V
ATPase complex from both sources. Towards this end, we have constructed a cDNA
library from lemon fruit and cloned it into a similar shuttle vector to the one
of the A. thaliana cDNA library, which is commercially available. In this work,
we report the cloning and expression of VMA10 from both sources, two isoforms of
the lemon proteolipid (VMA3) and the lemon homologue of yeast VPH1/STV1 subunit,
LEMAC.
PMID- 11004468
TI - Biological nano motor, ATP synthase F(o)F(1): from catalysis to gammaepsilonc(10
12) subunit assembly rotation.
AB - Proton translocating ATPase (ATP synthase), a chemiosmotic enzyme, synthesizes
ATP from ADP and phosphate coupling with the electrochemical ion gradient across
the membrane. This enzyme has been studied extensively by combined genetic,
biochemical and biophysical approaches. Such studies revealed a unique mechanism
which transforms an electrochemical ion gradient into chemical energy through the
rotation of a subunit assembly. Thus, this enzyme can be defined as a nano motor
capable of coupling a chemical reaction and ion translocation, or more simply, as
a protein complex carrying out rotational catalysis. In this article, we briefly
discuss our recent work, emphasizing the rotation of subunit assembly
(gammaepsilonc(10-12)) which is formed from peripheral and intrinsic membrane
subunits.
PMID- 11004469
TI - Critical evaluation of the one- versus the two-channel model for the operation of
the ATP synthase's F(o) motor.
AB - The mechanism of converting an electrochemical gradient of protons or Na(+) ions
across the membrane into rotational torque by the F(o) motor of the ATP synthase
has been described by a two-channel model or by a one-channel model. Experimental
evidence obtained with the F(o) motor from the Propionigenium modestum ATP
synthase is described which is in accordance with the one-channel model, but not
with the two-channel model. This evidence includes the ATP-dependent occlusion of
one (22)Na(+) per ATP synthase with a mutated Na(+)-impermeable a subunit or the
Na(+)(in)/(22)Na(+)(out) exchange which is not affected by modifying part of the
c subunit sites with dicyclohexylcarbodiimide.
PMID- 11004470
TI - The role of the D- and K-pathways of proton transfer in the function of the haem
copper oxidases.
AB - The X-ray structures of several haem-copper oxidases now at hand have given
important constraints on how these enzymes function. Yet, dynamic data are
required to elucidate the mechanisms of electron and proton transfer, the
activation of O(2) and its reduction to water, as well as the still enigmatic
mechanism by which these enzymes couple the redox reaction to proton
translocation. Here, some recent observations will be briefly reviewed with
special emphasis on the functioning of the so-called D- and K-pathways of proton
transfer. It turns out that only one of the eight protons taken up by the enzyme
during its catalytic cycle is transferred via the K-pathway. The D-pathway is
probably responsible for the transfer of all other protons, including the four
that are pumped across the membrane. The unique K-pathway proton may be
specifically required to aid O-O bond scission by the haem-copper oxidases.
PMID- 11004471
TI - A re-examination of the structural and functional consequences of mutation of
alanine-128 of the b subunit of Escherichia coli ATP synthase to aspartic acid.
AB - The effects of mutation of residue Ala-128 of the b subunit of Escherichia coli
ATP synthase to aspartate on the structure of the subunit and its interaction
with the F(1) sector were analyzed. Determination of solution molecular weights
by sedimentation equilibrium ultracentrifugation revealed that the A128D mutation
had little effect on dimerization in the soluble b construct, b(34-156). However,
the mutation caused a structural perturbation detected through both a 12%
reduction in the sedimentation coefficient and also a reduced tendency to form
intersubunit disulfide bonds between cysteine residues inserted at position 132.
Unlike the wild-type sequence, the A128D mutant was unable to interact with F(1)
ATPase. These results indicate that the A128D mutation caused a structural change
in the C-terminal region of the protein, preventing the binding to F(1) but
having little or no effect on the dimeric nature of b.
PMID- 11004472
TI - Light-induced FTIR difference spectroscopy of the S(2)-to-S(3) state transition
of the oxygen-evolving complex in Photosystem II.
AB - We have applied flash-induced FTIR spectroscopy to study structural changes upon
the S(2)-to-S(3) state transition of the oxygen-evolving complex (OEC) in
Photosystem II (PSII). We found that several modes in the difference IR spectrum
are associated with bond rearrangements induced by the second laser flash. Most
of these IR modes are absent in spectra of S(2)/S(1), of the acceptor-side non
heme ion, of Yradical(D)/Y(D) and of S(3)'/S(2)' from Ca-depleted PSII
preparations. Our results suggest that these IR modes most likely originate from
structural changes in the oxygen-evolving complex itself upon the S(2)-to-S(3)
state transition in PSII.
PMID- 11004473
TI - Proton transfer from glutamate 286 determines the transition rates between oxygen
intermediates in cytochrome c oxidase.
AB - We have investigated the electron-proton coupling during the peroxy (P(R)) to oxo
ferryl (F) and F to oxidised (O) transitions in cytochrome c oxidase from
Rhodobacter sphaeroides. The kinetics of these reactions were investigated in two
different mutant enzymes: (1) ED(I-286), in which one of the key residues in the
D-pathway, E(I-286), was replaced by an aspartate which has a shorter side chain
than that of the glutamate and, (2) ML(II-263), in which the redox potential of
Cu(A) is increased by approximately 100 mV, which slows electron transfer to the
binuclear centre during the F-->O transition by a factor of approximately 200. In
ED(I-286) proton uptake during P(R)-->F was slowed by a factor of approximately
5, which indicates that E(I-286) is the proton donor to P(R). In addition, in the
mutant enzyme the F-->O transition rate displayed a deuterium isotope effect of
approximately 2.5 as compared with approximately 7 in the wild-type enzyme. Since
the entire deuterium isotope effect was shown to be associated with a single
proton-transfer reaction in which the proton donor and acceptor must approach
each other (M. Karpefors, P. Adelroth, P. Brzezinski, Biochemistry 39 (2000)
6850), the smaller deuterium isotope effect in ED(I-286) indicates that proton
transfer from E(I-286) determines the rate also of the F-->O transition. In ML(II
263) the electron-transfer to the binuclear centre is slower than the intrinsic
proton-transfer rate through the D-pathway. Nevertheless, both electron and
proton transfer to the binuclear centre displayed a deuterium isotope effect of
approximately 8, i.e., about the same as in the wild-type enzyme, which shows
that these reactions are intimately coupled.
PMID- 11004474
TI - Steady-state tyrosine fluorescence to study the lipid-binding properties of a
wheat non-specific lipid-transfer protein (nsLTP1).
AB - The binding properties of a wheat non-specific lipid-transfer protein (nsLTP1)
for different mono- and diacylated lipids was investigated. Lipids varied by
their chain length, unsaturation and/or polar head group. In the case of fatty
acid or lysophospholipid with a C10 chain length, no interaction can be measured,
while poor affinity is reported for a C12 chain length. The dissociation constant
(K(d)) is about 0.5 uM independent of chain length from C14 to C18. The same
affinity is obtained for C18 fatty acids with one or two unsaturations, whatever
the cis-trans double bond isomery. In all cases, the number of binding sites, n,
by protein ranges between 1.6 and 1.9, suggesting that two lipids can fit within
the protein. omega-Hydroxy-palmitic acid, a natural monomer of cutin polymer, is
found to interact with nsLTP1 with a K(d) of 1 uM and n=2. In contrast with
previous data that reported the binding of the anionic diacylated phospholipid,
DMPG (Sodano et al., FEBS Lett. 416 (1997) 130-134), nsLTP1 is not able to bind
dimyristoylphosphatidylcholine, dimyristoylphosphatidic acid, palmitoyl
oleoylphosphatidylcholine or palmitoyl-oleoylphosphatidylglycerol added as
liposomes or solubilized in ethanol. However, when both nsLTP1 and lipids are
first solubilized in methanol, and then in the buffer, it was evidenced that the
protein can bind these lipids. These results suggest that lipid-lipid
interactions play an essential role in the binding process of plant nsLTP1 as
previously mentioned for other lipid-transfer proteins.
PMID- 11004475
TI - Plasma membrane coating with cationic silica particles and osmotic shock alters
the morphology of bovine aortic endothelial cells.
AB - We have used a published method of membrane preparation based on the precoating
of the apical membrane of aortic endothelial cells with cationic silica
microbeads (with or without polyacrylic acid) in combination with an osmotic
shock and mechanical shearing to isolate the apical from the basal plasma
membranes of these cells, in vitro. After labeling of the plasma membrane of
adherent endothelial cells with a fluorescent derivative of phosphatidylcholine
and by using laser confocal fluorescence scanning microscopy, we found that this
method of membrane isolation rapidly induced invaginations of the basal plasma
membrane to an extent which makes this method unsuitable for further membrane
lipid analysis. Morphological analysis of the cells and fluorescence recovery
after photobleaching experiments on the plasma membranes were performed at each
step of the purification procedure and showed that only hypotonic shock and
mechanical shearing of the cells enabled the basal plasma membranes to be
purified without significant morphological changes.
PMID- 11004477
TI - The novel anti-tumour agent oxamflatin differentially regulates urokinase and
plasminogen activator inhibitor type 2 expression and inhibits urokinase-mediated
proteolytic activity.
AB - Cell surface, urokinase (u-PA)-mediated, plasminogen activation has recently been
recognised as a process integral to extracellular matrix degradation. The primary
inhibitor of u-PA activity in the extracellular matrix is plasminogen activator
inhibitor type 2 (PAI-2), a serine protease inhibitor. The malignant metastatic
phenotype is associated with excessive and uncontrolled, tumour cell-associated,
u-PA-mediated, extracellular matrix degradation. Inhibition of the malignant
metastatic phenotype via induction of PAI-2 expression and/or inhibition of u-PA
expression may represent a novel means via which the metastatic phenotype can be
arrested. Agents capable of inducing PAI-2 and/or inhibiting u-PA activity may
restrict u-PA-mediated tumour cell proteolysis and facilitate in the development
of therapeutic strategies to combat malignant disease. We have identified the
hydroxamic acid derivative oxamflatin, previously noted to revert the malignant
phenotype in K-ras-transformed NIH-3T3 cells, as capable of upregulating PAI-2
and simultaneously suppressing u-PA expression in two different cell systems. In
addition, zymographic analysis indicated that oxamflatin treatment results in a
significant reduction in u-PA proteolytic activity in both HT-1080 fibrosarcoma
and U-937 histiocytic lymphoma cells. We postulate that oxamflatin represents a
novel means by which induction of PAI-2 and concomitant inhibition of u-PA gene
and protein expression can be achieved and may be of benefit in inhibiting the
malignant metastatic phenotype.
PMID- 11004478
TI - Isolation and characterization of a novel liver-specific gene, hepassocin,
upregulated during liver regeneration.
AB - By differential cDNA cloning coupled with Xenopus oocyte expression screening, we
isolated a cDNA encoding a novel protein, termed 'hepassocin', the expression of
which is upregulated in the regenerating rat liver. The cDNA contained a single
open reading frame encoding a protein of 314 amino acids (ca. 34 kDa), including
24 amino acids of signal sequence. The protein expressed from the cDNA in Verots
cells had activity to stimulate DNA synthesis in primary rat hepatocytes and was
of 66 kDa or 34 kDa, under non-reducing or reducing conditions, respectively.
Using an affinity column conjugated with the antibody raised against a peptide in
a hydrophilic region, we purified hepassocin from the rat liver: it had a DNA
synthesis-stimulating activity in hepatocytes. The hepassocin obtained here was
66 kDa, and the 34 kDa protein obtained under reducing conditions contained five
cysteine residues, indicating that hepassocin is active as a homodimer. Northern
blot analysis revealed that hepassocin mRNA (1.4 kb in length) occurred only in
the liver, and in situ hybridization studies revealed its presence in parenchymal
hepatocytes but not in endothelial cells. Furthermore, the expression of
hepassocin mRNA was upregulated during compensatory hyperplasia after partial
hepatectomy and regeneration after galactosamine treatment in the rat liver.
These results suggest that hepassocin plays an important role in stimulating
liver cell growth, through an autocrine mechanism.
PMID- 11004479
TI - Transforming growth factor-beta(1) regulation of surfactant protein B gene
expression is mediated by protein kinase-dependent intracellular translocation of
thyroid transcription factor-1 and hepatocyte nuclear factor 3.
AB - The transforming growth factor-beta (TGF beta) polypeptides control a variety of
cellular processes including organogenesis and cellular proliferation and
differentiation. In the developing lung, TGF beta(1) treatment inhibits airway
branching and expression of the genes for surfactant proteins (SP). Many effects
of TGF beta are mediated at the level of gene transcription but there is limited
information regarding signaling pathways and target transcription factors. In
this study with human pulmonary adenocarcinoma H441 cells, we investigated TGF
beta(1) effects on SP-B, a protein which is essential for normal function of
pulmonary surfactant. TGF beta(1) (10 ng/ml) reduced SP-B mRNA content in a time
dependent fashion, and transient transfection studies localized responsiveness to
the region of the SP-B promoter (-112/-72 bp) containing binding sites for
thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear factor 3 (HNF3),
transcription factors that are important enhancers of SP gene expression. Using
electrophoretic mobility shift assay and immunofluorescence, we demonstrated
rapid accumulation of these transcription factors in the cytoplasm and subsequent
loss from the nucleus on TGF beta(1) treatment of both adenocarcinoma cells and
cultured human fetal lung. TGF beta(1) treatment caused intracellular
translocation of protein kinase C and effects of TGF beta(1) were mostly
abrogated in the presence of the protein kinase inhibitor calphostin C. We
conclude that TGF beta(1), acting via protein phosphorylation, blocks nuclear
translocation of TTF-1 and HNF3 which results in down-regulation of the SP-B gene
and presumably other pulmonary genes which are transactivated by these factors.
PMID- 11004480
TI - Localization, expression and genomic structure of the gene encoding the human
serine protease testisin.
AB - Testisin is a recently identified human serine protease expressed by premeiotic
testicular germ cells and is a candidate tumor suppressor for testicular cancer.
Here, we report the characterization of the gene encoding testisin, designated
PRSS21, and its localization on the short arm of human chromosome 16 (16p13.3)
between the microsatellite marker D16S246 and the radiation hybrid breakpoint
CY23HA. We have further refined the localization to cosmid 406D6 in this interval
and have established that the gene is approximately 4. 5 kb in length, and
contains six exons and five intervening introns. The structure of PRSS21 is very
similar to the human prostasin gene (PRSS8) which maps nearby on 16p11.2,
suggesting that these genes may have evolved through gene duplication. Sequence
analysis showed that the two known isoforms of testisin are generated by
alternative pre-mRNA splicing. A major transcription initiation site was
identified 97 nucleotides upstream of the testisin translation start and conforms
to a consensus initiator element. The region surrounding the transcription
initiation site lacks a TATA consensus sequence, but contains a CCAAT sequence
and includes a CpG island. The 5'-flanking region contains several consensus
response elements including Sp1, AP1 and several testis-specific elements.
Analysis of testisin gene expression in tumor cell lines shows that testisin is
not expressed in testicular tumor cells but is aberrantly expressed in some tumor
cell lines of non-testis origin. These data provide the basis for identifying
potential genetic alterations of PRSS21 that may underlie both testicular
abnormalities and tumorigenesis.
PMID- 11004481
TI - Distribution of mRNA encoding B78/apj, the rat homologue of the human APJ
receptor, and its endogenous ligand apelin in brain and peripheral tissues.
AB - The human APJ receptor is a G protein-coupled receptor which functions as an
efficient alternative co-receptor for a number of human immunodeficiency virus
type 1 and simian immunodeficiency virus strains. We have cloned the rat APJ
receptor, which we term B78/apj, and have mapped the mRNA distribution of both
the receptor and its natural ligand apelin in rat tissues. Northern blot analysis
showed a similar pattern of expression for B78/apj and apelin mRNAs with
hybridising transcripts seen in the lung, heart, skeletal muscle, kidney, brain
and liver. In situ hybridisation histochemistry studies revealed intense B78/apj
gene expression in the parenchyma of the lung, a sub-population of glomeruli in
the kidney, the corpora lutea of the ovary and isolated cells of the anterior
lobe of the pituitary. B78/apj mRNA had a striking and unique distribution within
the central nervous system (CNS) where receptor expression was found in cells
within the meninges around the brain, in the posterior magnocellular and medial
parvocellular areas of the hypothalamic paraventricular nucleus and in the
supraoptic nucleus. This hypothalamic distribution offers a possible specific
role of this receptor in mediating neuroendocrine responses in the CNS.
PMID- 11004482
TI - Cloning of cDNAs encoding retinoic acid receptors RAR gamma 1, RAR gamma 2, and a
new splicing variant, RAR gamma 3, from Aambystoma mexicanum and characterization
of their expression during early development.
AB - To analyze retinoic acid (RA) receptor (RAR) expression during early development
in the urodele embryo, we have isolated cDNAs for four members of the axolotl
(Ambystoma mexicanum) RAR family, namely RAR alpha (NR1B1), aRAR gamma 1
(NR1B3a), aRAR gamma 2 (NR1B3b), and a new splicing variant of aRAR gamma 2, aRAR
gamma 3 (NR1B3c), which contains an insertion of five hydrophobic amino acids in
the C-terminal region of the DNA binding domain. The temporal expression pattern
of the RAR gamma isoforms was established by RT-PCR using total RNA from embryos
of different stages. The expression of aRAR gamma 2 coincides with neurulation
and is enhanced in the extremities of the embryo's anteroposterior axis. The aRAR
gamma 3 is specifically expressed during gastrulation and early neurulation,
whereas aRAR gamma 1 is expressed later during organogenesis. Global aRAR gamma 2
mRNA levels, as well as their spatio-temporal expression pattern in the neurula,
were not affected by treatment with RA. These results show that several RARs are
expressed in the axolotl embryo during early development, and reveal the
existence of a new RAR gamma variant.
PMID- 11004483
TI - Characterization of two putative histone deacetylase genes from Aspergillus
nidulans.
AB - In eukaryotic organisms, acetylation of core histones plays a key role in the
regulation of transcription. Multiple histone acetyltransferases (HATs) and
histone deacetylases (HDACs) maintain a dynamic equilibrium of histone
acetylation. The latter form a highly conserved protein family in many eukaryotic
species. In this paper, we report the cloning and sequencing of two putative
histone deacetylase genes (rpdA, hosA) of Aspergillus nidulans, which are the
first to be analyzed from filamentous fungi. Hybridization with a chromosome
specific cosmid library of A. nidulans allowed the localization of rpdA to
chromosome III and hosA to chromosome II, respectively. PCR analyses and Southern
hybridization experiments revealed that no further members of the RPD3 family are
present in the genome of the fungus. Although sequence alignment displays
significant amino acid similarity to other eukaryotic RPD3-type deacetylases, the
deduced RPDA sequence reveals an unusual 200-amino acid extension at the C
terminus. Expression of both genes was determined by RNA blot analysis. Treatment
of the cells with trichostatin A (TSA), a potent inhibitor of HDACs, was found to
stimulate expression of rpdA of A. nidulans.
PMID- 11004484
TI - Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11)
during myeloid differentiation of HL60 cells.
AB - The expression of human purinergic P2 receptors (P2X1-7 and P2Y1-11) as well as
the ecto-enzymes apyrase (CD39) and 5'-nucleotidase (CD73) was investigated on
the nucleic acid level during granulocytic and monocytic differentiation of HL60
cells and on peripheral human blood leukocytes. RT-PCR and dot-blot hybridization
assays indicated that mRNA transcripts of all analyzed P2 receptors apart from
the P2X3 receptor were expressed during myeloid development of HL60 cells,
showing a distinct regulation during the course of differentiation. In blood
leukocytes, transcripts of P2X5, P2X7 and all P2Y receptors, except for P2Y6,
receptor were found. CD39 and CD73 showed a marked upregulation during myeloid
maturation. Functional analysis of P2 receptor-mediated intracellular Ca(2+)
increase after stimulation with ATP revealed no change during granulocytic
differentiation, but showed a strong attenuation in both potency and efficacy
during monocytic development of HL60 cells.
PMID- 11004485
TI - cDNA structure, genomic organization, and promoter analysis of the mouse
intestinal peptide transporter PEPT1.
AB - We describe in this report the cDNA structure, functional characteristics,
genomic organization, and promoter analysis of the mouse H(+)-coupled low
affinity peptide transporter PEPT1. The mouse PEPT1 cDNA cloned from a kidney
cDNA library is approximately 3.1 kb long and encodes a protein of 709 amino
acids. When expressed heterologously in mammalian cells and in Xenopus laevis
oocytes, mouse PEPT1 mediates H(+)-coupled electrogenic transport of the
dipeptide glycylsarcosine. The mouse pept1 gene, cloned from a genomic DNA
library in bacterial artificial chromosome, is approximately 38 kb long and
consists of 23 exons and 22 introns. 5'-Rapid amplification of cDNA ends with
poly(A)(+) RNA from mouse intestine has identified the transcription start site
that lies 31 bp upstream of the translation start site. The promoter region
upstream of the transcription start site does not contain the TATA box but
possesses three GC boxes which are the binding sites for the transcription
activator SP1. Functional analysis of the promoter region using the luciferase
reporter assay in Caco-2 cells (a human intestinal cell line that express PEPT1
constitutively) and five different 5'-deletion fragments of the promoter has
shown that essential promoter/enhancer elements are present within 1140 bp
upstream of the transcription start site.
PMID- 11004487
TI - Analysis of the promoter region of the human FcRn gene.
AB - The 5'-flanking region of the human FcRn alpha-chain gene was analyzed for its
ability to directly express the chloramphenicol acetyltransferase (CAT) reporter
gene in NIH3T3 and Lu106 cells. Transient transfection of the CAT constructs
revealed that there was promoter activity in the region -660 to +300 of the 5'
flanking sequence. Electrophoretic mobility-shift assays showed that there are
functional binding sites for Sp1 or Sp1-like factors, AP1 or a related factor,
and additional unidentified proteins in the promoter region.
PMID- 11004486
TI - Interleukin-6 modulates interferon-regulated gene expression by inducing the
ISGF3 gamma gene using CCAAT/enhancer binding protein-beta(C/EBP-beta).
AB - Although interleukin-6 (IL-6) alone does not induce the expression of IFN
stimulated genes (ISG), a low dose priming of cells with IL-6 strongly enhances
the cellular responses to interferon-alpha (IFN-alpha). This effect of IL-6 is
not due to superstimulation of the JAK-STAT pathway. Rather, IL-6 induces
expression of ISGF3 gamma (p48), a subunit of the multimeric transcription factor
ISGF3. As a result IFN-alpha robustly activates gene transcription in IL-6 primed
cells. We have shown earlier that the transcription of ISGF3 gamma gene is
regulated through a novel element GATE (gamma-IFN activated transcriptional
element). We show here IL-6 induces the ISGF3 gamma gene through GATE.
Transcription factor C/EBP-beta is required for inducing ISGF3 gamma gene
expression through GATE. A mutant C/EBP-beta inhibits the IL-6 inducible ISGF3
gamma gene expression through GATE. Together, these results establish a molecular
basis for the synergy between IFNs and IL-6.
PMID- 11004488
TI - Structural organization and expression of the gaegurin 4 gene of Rana rugosa.
AB - Gaegurin 4 (GGN4) is a member of the antimicrobial peptide subfamily isolated
from the skin of Rana rugosa. We cloned gDNA encoding GGN4 to study its gene
organization and regulation of expression. The GGN4 gene occurs in single copy in
the R. rugosa genome and contains a single intron of about 3.4 kb. The
transcription start site is located 68 bases upstream of the translation
initiation codon. The GGN4 gene was expressed both in Xenopus kidney epithelial
cells (A6) and in Xenopus oocytes using the chloramphenicol acetyltransferase
reporter gene system. The 5' flanking region of the GGN4 gene contains a dl
binding site that is known to regulate acute phase immune response related gene
expression in mammals and insects. The dl protein bound specifically to the GGN4
gene promoter region. Mutants that serially delete the 5' flanking region show
that removal of the dl binding site inhibited GGN4 gene expression in both A6
cells and Xenopus oocytes. From these results, we propose that expression of the
GGN4 gene may be regulated by the region containing the dl element which plays a
key role in the regulation of antimicrobial peptide genes in Drosophila and
mammals.
PMID- 11004489
TI - Cloning and characterization of a novel RNA-binding protein SRL300 with RS
domains.
AB - AT-rich element binding factor 1 (ATBF1) mRNA encodes a transcription factor
implicated in neuronal differentiation. A cDNA for the protein that can bind the
5'-noncoding sequence of the ATBF1 mRNA was cloned. The deduced protein, termed
SRL300, contains a unique RNA-binding region, two large RS domains and many
phosphorylation sites. SRL300 protein was detected in both human and rat cells.
PMID- 11004490
TI - Identification of a novel platelet-derived growth factor-like gene, fallotein, in
the human reproductive tract.
AB - We isolated the cDNA of a novel platelet-derived growth factor-like gene from
human endometrium. The gene was named fallotein; it was 3007 bases in length, and
encoded a protein of 345 amino acids. Antiserum against the fallotein protein can
recognize a specific protein in the fallopian tube, with a molecular size in
accordance with the anticipated size of fallotein. Fallotein mRNA is expressed in
two molecular sizes, 3.8 and 2.9 kb, with the former being more abundant. High
expression of the gene was found in the prostate, testis, and uterus. A weaker
expression signal was found in the spleen, thymus, and small intestine, but
expression of fallotein in the colon and peripheral blood leukocytes was
negligible.
PMID- 11004491
TI - Structure and stress-related expression of two cDNAs encoding proteinase
inhibitor II of Nicotiana glutinosa L.
AB - Two cDNAs, pNGPI-1 and pNGPI-2, encoding Nicotiana glutinosa proteinase inhibitor
II (PI-II) have been cloned, sequenced and identified. The deduced amino acid
sequences are 54-82% identical to those of other plant PI-II. The NGPI-1 protein
is composed of eight repeated domains, while NGPI-2 contains six repeated
regions, each with a putative reactive site. The expression of NGPI-1 is highly
regulated in a developmental- and tissue-specific manner, with the transcript
being detected in young leaves and floral organs of N. glutinosa plants. In
mature leaves, the NGPI-1 gene is rapidly activated by distinct temporal
induction patterns in response to pathogen-related (biotic) and wound-related
(abiotic) stresses.
PMID- 11004492
TI - Genomic organization and transcriptional regulation of maize ZmRR1 and ZmRR2
encoding cytokinin-inducible response regulators.
AB - Maize genomic clones encoding cytokinin-inducible response regulators, ZmRR1 and
ZmRR2, have been isolated. In comparison with the corresponding cDNAs, ZmRR2 was
found to be interrupted in the translated region by an intron whereas ZmRR1 was
not. The 5'-flanking regions of the two genes shared conserved regions and
putative cis-elements, which had been identified in maize or other plant species.
The run-on transcription assay and the analysis of stable maize transformants of
ZmRR1 promoter-beta-glucuronidase fusion gene revealed that the accumulation of
the transcripts in response to cytokinins is, at least in parts, attributed by
transcriptional activation.
PMID- 11004493
TI - Nucleotide sequence of cDNA clones coding for a brain-type fatty acid binding
protein and its tissue-specific expression in adult zebrafish (Danio rerio).
AB - We have determined the nucleotide sequence for two cDNA clones coding for a fatty
acid binding protein (FABP) from zebrafish (Danio rerio). Comparison of the
sequence with GenBank entries revealed extensive amino acid identity between this
zebrafish FABP and brain FABPs (B-FABP) from other species. The zebrafish B-FABP
cDNA hybridized to single restriction fragments of total zebrafish genomic DNA
digested with the restriction endonucleases BglII or EcoRI suggesting that a
single copy of the B-FABP gene is present in the zebrafish genome. Northern blot
analysis demonstrated that the zebrafish B-FABP mRNA is approximately 850
nucleotides in length. In situ hybridization revealed that the B-FABP mRNA was
expressed in the periventricular gray zone of the optic tectum of the adult
zebrafish brain.
PMID- 11004494
TI - cDNA sequence and tissue-specific expression of a basic liver-type fatty acid
binding protein in adult zebrafish (Danio rerio).
AB - We have determined the nucleotide sequence for a cDNA clone derived from
zebrafish (Danio rerio) that codes for a fatty acid binding protein (FABP). Amino
acid sequence similarity of the zebrafish FABP was highest to FABPs isolated from
the livers of catfish, chicken, salamander and iguana. The open-reading frame of
the zebrafish FABP cDNA codes for a protein of 14.0 kDa with a calculated
isoelectric point of 8.8. The zebrafish liver-type FABP (L-FABP) cDNA hybridized
to single restriction fragments of total zebrafish genomic DNA digested with the
restriction endonucleases HaeIII or EcoRI suggesting that a single copy of the L
FABP gene is present in the zebrafish genome. Northern blot analysis demonstrated
that the zebrafish L-FABP cDNA hybridized to a transcript of 700 nucleotides in
total zebrafish RNA. In situ hybridization and emulsion autoradiography revealed
that the L-FABP was expressed exclusively in the liver of the adult zebrafish.
Based on amino acid sequence similarity, the isoelectric point and its tissue
specific pattern of expression, we conclude that this zebrafish FABP belongs to
the basic liver-type FABPs only found, thus far, in non-mammalian vertebrates.
PMID- 11004495
TI - Characterisation of a cysteine protease cDNA from Lolium multiflorum leaves and
its expression during senescence and cytokinin treatment.
AB - A cysteine protease cDNA clone (See1) highly homologous to barley aleurain was
isolated from Lolium multiflorum leaves. During leaf senescence, expression of
the See1 mRNA and protein was strongly enhanced. In dark-incubated leaf segments,
cytokinin delayed senescence and reduced expression of both See1 mRNA and
protein.
PMID- 11004496
TI - New isoforms of cytochrome c oxidase subunit IV in tuna fish.
AB - In the present study, the cDNA sequences of cytochrome c oxidase subunit IV
isoforms from tuna fish are reported. The cDNAs share 57% identity among each
other and the deduced amino acid sequences of the mature proteins 56% identity.
Until now, only in yeast are two isoforms of the corresponding subunit V known,
which are expressed in response to the oxygen supply. The hypothetical function
of the new isoforms in fish for adaptation to different oxygen partial pressures
in tissues of higher organisms is discussed.
PMID- 11004497
TI - Molecular characterization of Drosophila melanogaster dihydropteridine reductase.
AB - Dihydropteridine reductase (DHPR) catalyzes the NAD(P)H-mediated reduction of
quinonoid dihydropteridine as a part of pterin-dependent aromatic amino acid
hydroxylation. We isolated a fragment of Drosophila DHPR gene by PCR using
degenerate primers. By screening a cDNA library, we obtained full-length clones.
The predicted amino acid sequence of the Drosophila DHPR protein was highly
homologous to other species including human and mouse. In particular, the Tyr
(Xaa)(3)-Lys motif, known as the NAD(P)H binding domain, and most amino acids
relevant to quinonoid dihydropteridine binding site are identical to human DHPR.
The recombinant DHPR protein expressed in Escherichia coli showed DHPR enzyme
activity. Northern blot analysis revealed two transcripts of 1.1 and 0.9 kb.
Genomic DNA sequencing revealed that the gene consists of two exons interrupted
by a single 96-bp intron. The two transcripts have alternative promoters, both
having no putative TATA box or CAAT box, but sharing a common poly(A)(+) signal.
The existence of two alternative promoters suggests that each transcript be
regulated independently through different stimuli. Further study is needed to
examine the expression and function of the two alternative transcripts.
PMID- 11004498
TI - Isolation and sequence of the human cytochrome c oxidase subunit VIIaL gene.
AB - The gene for human cytochrome c oxidase subunit VIIa liver isoform (COX7AL) was
isolated and its sequence determined and analyzed. The three introns of the gene
are considerably larger than those of the heart isoform of subunit VIIa (COX7AH),
but the position of the introns relative to the cDNA sequences is homologous
between the two genes. Comparison with other isolated COX7AL genes suggests that
the promoter region binding motifs for transcription factors have evolved along
with the coding region. In fibroblasts cultured originally from a Leigh's disease
patient, a shortened COX7AL cDNA was identified by RT-PCR, consisting of exon I
joined to exon IV, omitting exons II and III. No mutation could be identified in
COX7AL of the patient, suggesting that the shortened cDNA is due to an alteration
of the genome during cell culture. A surprising transcription of COX7AH was
observed in cultured fibroblasts, suggesting a potential utility of these cells
for study of its gene expression.
PMID- 11004499
TI - Molecular cloning of cDNA encoding a ubiquitin-activating enzyme (E1) from
goldfish (Carassius auratus) and expression analysis of the cloned gene.
AB - Destruction of cyclin B is required to the mitotic and meiotic cycles. A cyclin
specific ubiquitinating system, including ubiquitin-activating enzyme (E1), is
thought to be responsible for cyclin B destruction. Here we present the cloning,
sequencing and expression analysis of goldfish, Carassius auratus, E1 from
goldfish ovary. The cloned cDNA is 4069 bp long and encodes 1059 amino acids. The
deduced amino acid sequence is highly homologous to E1 from other species.
Recombinant goldfish E1 could transfer ubiquitin to cyclin-selective ubiquitin
conjugating enzyme. Tissue distribution revealed a single 4.0-kb message
ubiquitous among tissues.
PMID- 11004500
TI - Identification of a novel human tRNA(Ser(CGA)) functional in murine leukemia
virus replication.
AB - We have identified a human tRNA(Ser) isoacceptor matching the UCG codon. The tRNA
was discovered via its ability to act in reverse transcription of a murine
leukemia virus vector containing a complementary tRNA primer binding site (Lund
et al., Nucleic Acids Res., 28 (2000) 791-799). The tRNA(Ser(CGA)) was detected
in cell lines of human, monkey and mouse origin. The UCG codon is the most rarely
used codon in human genes. The cloned human tRNA(Ser(CGA)) gene encodes an 85
nucleotide, intron-less tRNA, contains a consensus split intragenic promoter and
is located at region p21.3-22.2 on chromosome 6. The integrity and functionality
of the cloned tRNA(Ser(CGA)) gene was verified by in vitro transcription analysis
in HeLa nuclear extracts.
PMID- 11004501
TI - Cloning, sequencing and expression of the tetraheme cytochrome c(3) from
Desulfovibrio gigas.
AB - The gene encoding the tetraheme cytochrome c(3) from Desulfovibrio gigas was
cloned and sequenced from a 2.7-kb EcoRI-PstI insert of D. gigas DNA. The derived
amino acid sequence showed that the D. gigas cytochrome c(3) is synthesized as a
precursor protein with an N-terminal signal peptide sequence of 25 residues and
allowed the correction of the previous reported amino acid sequence (Matias et
al. Protein Science 5 (1996) 1342-1354). Expression in D. vulgaris
(Hildenborough) was possible by conjugal transfer of a recombinant broad-host
range vector pSUP104 containing a SmaI fragment of the D. gigas cytochrome c(3)
gene. Biochemical, immunological and spectroscopic analysis of the purified
protein showed that the recombinant cytochrome is identical to that isolated from
D. gigas.
PMID- 11004502
TI - Molecular cloning and expression of rat betacellulin cDNA.
AB - The cDNA encoding an entire open reading frame of rat betacellulin has been
cloned from rat kidney. Expression of this cDNA in COS7 cells showed a
significant amount of mitogenic activity in the culture media. Western blotting
of the cell lysates suggested that the membrane-anchored precursor was cleaved to
release its ectodomain very efficiently.
PMID- 11004503
TI - Differential developmental expression and cell type specificity of Dictyostelium
catalases and their response to oxidative stress and UV-light.
AB - Cells of Dictyostelium discoideum are highly resistant to DNA damaging agents
such as UV-light, gamma-radiation and chemicals. The genes encoding nucleotide
excision repair (NER) and base excision repair (BER) enzymes are rapidly
upregulated in response to UV-irradiation and DNA-damaging chemicals, suggesting
that this is at least partially responsible for the resistance of this organism
to these agents. Although Dictyostelium is also unusually resistant to high
concentrations of H(2)O(2), little is known about the response of this organism
to oxidative stress. To determine if transcriptional upregulation is a common
mechanism for responding to DNA-damaging agents, we have studied the
Dictyostelium catalase and Cu/Zn superoxide dismutase antioxidant enzymes. We
show that there are two catalase genes and that each is differentially regulated
both temporally and spatially during multicellular development. The catA gene is
expressed throughout growth and development and its corresponding enzyme is
maintained at a steady level. In contrast, the catB gene encodes a larger protein
and is only expressed during the final stages of morphogenesis. Cell type
fractionation showed that the CatB enzyme is exclusively localized to the
prespore cells and the CatA enzyme is found exclusively in the prestalk cells.
Each enzyme has a different subcellular localization. The unique developmental
timing and cell type distribution suggest that the role for catB in cell
differentiation is to protect the dormant spores from oxidative damage. We found
that exposure to H(2)O(2) does not result in the induction of the catalase,
superoxide dismutase, NER or BER mRNAs. A mutant with greatly reduced levels of
catA mRNA and enzyme has greatly increased sensitivity to H(2)O(2) but normal
sensitivity to UV. These results indicate that the natural resistance to
oxidative stress is not due to an ability to rapidly raise the level of
antioxidant or DNA repair enzymes and that the response to UV-light is
independent from the response to reactive oxygen compounds.
PMID- 11004504
TI - The genomic structure and promoter analysis of the human ABF-1 gene.
AB - The human ABF-1 gene is expressed in activated B-cells and Epstein-Barr virus
immortalized lymphoblastoid cell lines. ABF-1 represents the only member
belonging to the basic helix-loop-helix (bHLH) family of transcription factors
whose expression pattern is restricted to B-cells. ABF-1 forms heterodimeric
complexes with E2A to modulate gene transcription. We report the cloning and
characterization of the human ABF-1 gene and the promoter region. The gene spans
more than 3 kb and contains two exons. Exon 1 contains 274 bp of a 5'
untranslated sequence (UTR) while exon 2 contains 1097 bp of 3'-UTR. Promoter
analysis of the 5'-flanking region revealed no apparent B-cell-restricted control
elements within approximately 700 bp, but clearly demonstrated the presence of a
functional minimal promoter residing immediately upstream of the transcription
start site. Analysis of the region containing the minimal promoter activity
identified no CCAAT or TATA sequence. Lastly, we have assigned the ABF-1 gene to
human chromosome 8q21.1 using fluorescence in situ hybridization (FISH). The
cloning of the human ABF-1 gene will facilitate further biochemical and genetic
studies of its function in the regulation of B-cell differentiation.
PMID- 11004505
TI - Novel responses of ZRF, a variant of human MTF-1, to in vivo treatment with heavy
metals.
AB - Heavy metal-dependent transcriptional activation of metallothionein (MT) genes is
mediated by multiple enhancer sequences, metal responsive element (MRE), located
in the upstream region of the genes. Previously, we have reported purification of
a zinc-dependent MRE-binding protein, zinc regulatory factor (ZRF), from HeLa
cells, and have pointed to the close relationship between ZRF and mouse MRE
binding transcription factor-1 (MTF-1) according to the analysis of partial amino
acid sequences. By means of cDNA cloning and the product analyses, we show that
ZRF is a variant of human MTF-1 (hMTF-1), which carries a single amino acid
exchange in the zinc finger domain. Accordingly, ZRF is renamed hMTF-1b.
Expression of hMTF-1b in HeLa cells is constitutive at both mRNA and protein
levels, and is unaffected by treatment with cadmium (Cd). On the other hand, when
cells were fractionated into nuclear extract and cytosol, a large part of the
hMTF-1b was recovered in the cytosol fraction. A significant increase in the
amount of nuclear hMTF-1b occurs when cells are treated with various heavy
metals, including Cd, Zn, Cu and Ag, which is associated with concomitant
decrease in the amount recovered in the cytosol fraction. Since
immunocytochemical analysis revealed that intracellular distribution of hMTF-1b
is restricted to the nucleus irrespective of the heavy metal treatment, such an
increment in the nuclear extracts apparently results from promotion of nuclear
retention of hMTF-1b by the heavy metal treatment. Analysis by native gel
electrophoresis shows that the mobility of hMTF-1b significantly changes in
association with Cd treatment, raising the possibility that a conformational
change of hMTF-1b occurs in response to treatment with heavy metals in vivo.
PMID- 11004506
TI - Transcription of the catalytic 180-kDa subunit gene of mouse DNA polymerase alpha
is controlled by E2F, an Ets-related transcription factor, and Sp1.
AB - We have isolated a genomic DNA fragment spanning the 5'-end of the gene encoding
the catalytic subunit of mouse DNA polymerase alpha. The nucleotide sequence of
the upstream region was G/C-rich and lacked a TATA box. Transient expression
assays in cycling NIH 3T3 cells demonstrated that the GC box of 20 bp (at
nucleotides -112/-93 with respect to the transcription initiation site) and the
palindromic sequence of 14 bp (at nucleotides -71/-58) were essential for basal
promoter activity. Electrophoretic mobility shift assays showed that Sp1 binds to
the GC box. We also purified a protein capable of binding to the palindrome and
identified it as GA-binding protein (GABP), an Ets- and Notch-related
transcription factor. Transient expression assays in synchronized NIH 3T3 cells
revealed that three variant E2F sites near the transcription initiation site (at
nucleotides -23/-16, -1/+7 and +17/+29) had no basal promoter activity by
themselves, but were essential for growth-dependent stimulation of the gene
expression. These data indicate that E2F, GABP and Sp1 regulate the gene
expression of this principal replication enzyme.
PMID- 11004508
TI - Telomeric profiles and telomerase activity in turkey satellite cell clones with
different in vitro growth characteristics.
AB - The satellite cell population in postnatal skeletal muscle is heterogeneous
because individual satellite cells isolated from a single muscle have differing
abilities to proliferate under the same in vitro conditions. Telomeres are
structures found at the ends of all eukaryotic chromosomes that are characterized
by repetitive DNA sequences, and they are important in determining cellular
proliferation potential. The relationship between satellite cell proliferative
heterogeneity and telomeric DNA was examined by digesting genomic DNA from large
colony-forming and small-colony-forming turkey satellite cell clones with HinfI,
separating the restriction fragments on an agarose gel, and hybridizing the gels
with an oligonucleotide probe specific for telomeric DNA. Turkey satellite cells
generated telomeric restriction fragments up to approximately 180 kB. The large
colony-forming satellite cell clones had a larger proportion (P<0.05) of total
telomeric restriction fragments below 33 kB than the small-colony-forming
satellite cell clones. However, telomerase expression was detected in cultures
from large-colony-forming and small-colony-forming turkey satellite cells
suggesting that the differences in telomeric restriction fragments may not be
related to the differences in in vitro proliferative behavior and that telomerase
may contribute to the high in vitro growth capacity of turkey satellite cells.
PMID- 11004507
TI - Structure and genetic polymorphism of the mouse KCC1 gene.
AB - The KCC1 K-Cl cotransporter is a major regulator of erythroid and non-erythroid
cell volume, and the KCC1 gene is a candidate modifier gene for sickle cell
disease and other hemoglobinopathies. We have cloned and sequenced the mouse KCC1
(mKCC1) gene, defined its intron-exon junctions, and analyzed (AC)/(TG)
intragenic polymorphisms. A highly polymorphic (AC) repeat of mKCC1 intron 1 was
characterized in musculus strains, and used to prove lack of linkage between the
mKCC1 gene and the rol (resistant to osmotic lysis) locus. The intron 1 (AC)
repeat in CAST/Ei and SPRET/Ei was not only more divergent in length but also
underwent additional sequence variation. A dimorphic (TG) repeat in intron 2
distinguished CAST/Ei from other strains, and an intron 17 B1 Alu-like SINE
present in all musculus strains was found to be absent from intron 17 in
SPRET/Ei. These and additional described strain-specific polymorphisms will be
useful mapping and genetic tools in the study of mouse models of sickle cell
disease.
PMID- 11004509
TI - Functional cloning and mutational analysis of the human cDNA for
phosphoacetylglucosamine mutase: identification of the amino acid residues
essential for the catalysis.
AB - In Saccharomyces cerevisiae, phosphoacetylglucosamine mutase is encoded by an
essential gene called AGM1. The human AGM1 cDNA (HsAGM1) and the Candida albicans
AGM1 gene (CaAGM1) were functionally cloned and characterized by using an S.
cerevisiae strain in which the endogenous phosphoacetylglucosamine mutase was
depleted. When expressed in Escherichia coli as fusion proteins with glutathione
S-transferase, both HsAgm1 and CaAgm1 proteins displayed phosphoacetylglucosamine
mutase activities, demonstrating that they indeed specify
phosphoacetylglucosamine mutase. Sequence comparison of HsAgm1p with several
hexose-phosphate mutases yielded three domains that are highly conserved among
phosphoacetylglucosamine mutases and phosphoglucomutases of divergent organisms.
Mutations of the conserved amino acids found in these domains, which were
designated region I, II, and III, respectively, demonstrated that alanine
substitutions for Ser(64) and His(65) in region I, and for Asp(276), Asp(278),
and Arg(281) in region II of HsAgm1p severely diminished the enzyme activity and
the ability to rescue the S. cerevisiae agm1Delta null mutant. Conservative
mutations of His(65) and Asp(276) restored detectable activities, whereas those
of Ser(64), Asp(278), and Arg(281) did not. These results indicate that Ser(64),
Asp(278), and Arg(281) of HsAgm1p are residues essential for the catalysis.
Because Ser(64) corresponds to the phosphorylating serine in the E. coli
phosphoglucosamine mutase, it is likely that the activation of HsAgm1p also
requires phosphorylation on Ser(64). Furthermore, alanine substitution for
Arg(496) in region III significantly increased the K(m) value for N
acetylglucosamine-6-phosphate, demonstrating that Arg(496) serves as a binding
site for N-acetylglucosamine-6-phosphate.
PMID- 11004510
TI - Identification of cAMP analogue inducible genes in RAW264 macrophages.
AB - RNA was isolated from RAW264 cells treated with or without 8-Br-cAMP and the
differential display and subtractive hybridization methods were performed. One
hundred and twenty-five differentially displayed bands were identified. Upon
Northern blot analysis, only three of these bands were confirmed as cAMP
inducible mRNAs, named cI-1, cI-2, and cI-3 (for cAMP inducible genes 1-3). The
cI-3 probe was identical to a previously known gene, gly96. Using the novel cI-1
and cI-2 partial cDNAs as probes, a mouse macrophage cDNA library was screened
and the two full length genes were cloned, sequenced, and characterized as
encoding large hydrophobic proteins. One hundred and fifteen partial cDNA clones
from a subtractive hybridization library were also screened by Northern blot and
64 were found to be cAMP inducible. Of these, 45 represented 31 known unique
genes in the GenBank nr database (cI-4-34), and 19 clones representing 15 unique
sequences were not in the nr database (cI-35-49). One of the previously known
genes was ABC1, the Tangier disease gene, which was identified from four
independent partial cDNAs. ABC1 was upregulated in RAW cells by cAMP, concurrent
with the cAMP induction of lipid efflux to apolipoprotein A1.
PMID- 11004511
TI - Nucleotide sequence, genomic organization and cell-cycle-dependent expression of
a Chlamydomonas 14-3-3 gene.
AB - Members of the 14-3-3 protein family have been identified as regulatory elements
in intracellular signalling pathways and cell cycle control. Previously we
reported the nucleotide sequence of a 14-3-3 cDNA cloned from the unicellular
green alga Chlamydomonas reinhardtii. In this communication, we describe the
nucleotide sequence, the genomic organization and the cell-cycle-dependent
expression of the corresponding gene. The coding sequence of this gene was found
to be interrupted by four introns of 124, 116, 81, and 659 bp, respectively.
Introns 2-4 were found in conserved positions as compared to the Arabidopsis 14-3
3 genes. A counterpart to intron 1 absent in the Arabidopsis 14-3-3 genes was
found in the human 14-3-3 epsilon gene.
PMID- 11004512
TI - Spatiotemporal regulation of hnRNP M and 2H9 gene expression during mouse
embryonic development.
AB - Using the HeLa cell model along with an in vitro splicing system, we have
previously shown that hnRNP M and 2H9 are involved in the pre-mRNA splicing
process and most interestingly also in heat shock-induced transient splicing
arrest by transiently leaving the hnRNP complexes. Due to this unique regulatory
function in a mechanism that turns splicing on and off, these two hnRNPs appear
as important proteins for controlling gene expression. Here we investigated by in
situ hybridization and immunohistochemical staining techniques the expression
level of specific mRNA and protein during mouse embryonic development. HnRNP M
and 2H9 are found to be expressed at all examined stages (6.5-18.5 days post
coitum), in a differential manner, and at various levels depending on tissues,
cell types and also embryonic stages; fairly high levels of both hnRNPs are
always observed in the central nervous system. Furthermore, levels of
colocalizing protein and transcript are not always present in the same
proportion, thus suggesting a post-transcriptional regulation of hnRNP M and 2H9
gene expression. The complex spatiotemporal variations we observed might well
anticipate a role for these two hnRNPs also in modulating splicing, thereby
influencing gene expression and further many physiological processes.
PMID- 11004513
TI - Human CKIalpha(L) and CKIalpha(S) are encoded by both 2.4- and 4. 2-kb
transcripts, the longer containing multiple RNA-destablising elements.
AB - Casein kinase I (CKI) are a family of conserved second messenger-independent
serine/threonine protein kinases found in all eukaryotes. The avian and mammalian
CKI alpha isoform has four splice variants differing in the presence or absence
of 28 amino acids ('(L)' insertion) in the catalytic domain and/or 12 amino acids
('(S)' insertion) in the regulatory domain. Here we report the isolation of cDNAs
encoding human CKIalpha(L) and CKIalpha(S). We find human CKIalpha(L) has a
preference to phosphorylate phosvitin over casein, with a higher K(m) for casein
than phosvitin, the reverse being the case for human CKIalpha(S). Both human
CKIalpha(L), and CKIalpha(S) are derived from 4.2-kb mRNA transcripts and 2.4-kb
transcripts, the latter probably generated by use of an alternate polyadenylation
signal identified in the longer transcripts. The 4. 2-kb transcripts contain six
RNA-destabilising AU-rich element (ARE) motifs in the 3'-untranslated region
(UTR), while the 2.4-kb transcripts contain a single ARE motif. In vitro analysis
of CKI alpha 3'-UTR RNA sequences suggests that in HeLa cells, the longer 3'-UTR
transcripts are likely to degrade approximately 13 times faster than the shorter
3'-UTR transcripts. This is the first report of a kinase mRNA containing multiple
RNA-destabilising AREs in the longer of two mRNA transcripts.
PMID- 11004514
TI - Characterisation of the rat heparin-binding epidermal growth factor-like growth
factor gene promoter.
AB - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) gene
expression is strongly activated by a variety of extracellular stimuli, acting
through the Raf/MEK/MAP kinase pathway. To study the elements that respond to
this pathway, we have isolated and sequenced a fragment of the rat HB-EGF gene
promoter. By transfection of a series of promoter/reporter constructs into cells,
a minimal promoter element was demonstrated to lie between 448 bp upstream of the
transcriptional start site and 103 bp into the first exon of the gene. However co
transfection of the promoter constructs with a plasmid directing expression of
RafCAAX, an activated c-Raf-1 protein, gave a fold-stimulation of activity no
greater than that seen for the parental pGL3-Basic plasmid alone. In addition,
agonist stimulation of cell lines stably transfected with a HB-EGF
promoter/luciferase construct produced little or no increase in reporter enzyme
activity. These results suggest that the c-Raf-1 responsive elements lie outside
the tested region of the rat HB-EGF gene. However, it has been reported that a c
Raf-1 responsive element is present within the equivalent region of the mouse
gene. A comparison of the 5'-flanking regions of the mouse, rat and human HB-EGF
genes indicated that the mouse sequence diverges abruptly from that of the other
two species approximately 260 bp upstream of the transcriptional start site. PCR
analysis of mouse genomic DNA suggests that this sequence divergence is due to
DNA rearrangement during the cloning of the mouse gene. Additional studies are
therefore required to identify Raf/MAP kinase responsive elements in the HB-EGF
gene.
PMID- 11004515
TI - Genomic cloning, mapping, structure and promoter analysis of HEADPIN, a serpin
which is down-regulated in head and neck cancer cells.
AB - Headpin is a novel serine proteinase inhibitor (serpin) that is down-regulated in
squamous cell carcinoma of the oral cavity and in squamous cell carcinoma cell
lines of the head and neck. Using a panel of 18q21.3 YAC clones, we mapped and
cloned the HEADPIN gene. The gene spans 10 kb and is composed of eight exons and
seven introns. The genomic structure is identical with some other ovalbumin
serpins (ov-serpins) in terms of the numbers, position and phasing of the
intron/exon boundaries. HEADPIN was mapped within the serpin cluster in 18q21.3
between MASPIN and SCCA2 as follows: cen-MASPIN-HEADPIN-SCCA2-SCCA1-tel. The
transcription start site was determined and the promoter activity of the 5'
flanking region was analyzed. Luciferase promoter assays in HaCaT cells showed
that the -432 to -144 nucleotide region has functional promoter activity. The
activity of the promoter/enhancer was not observed in head and neck cancer cell
lines TU167 and UMSCC1 which lack headpin expression. These data suggest that the
differential expression of headpin in normal and carcinoma-derived cells is
regulated at the transcriptional level. Understanding the genomic organization
and transcriptional regulation of the ov-serpins clustered within 18q21. 3
provides a critical framework for assessing their potential role in cancer.
PMID- 11004516
TI - Cloning and gene expression of a novel human ribonucleoprotein.
AB - This paper reports on the cloning and characterization of a novel human
ribonucleoprotein, RBM8, containing a single RNA binding domain comprising the
two RNP-CS and RNP-2 consensus motifs. The protein has 55% identity to a segment
of a C. elegans ribonucleoprotein of unknown function. The RBM8 gene shows
ubiquitous tissue expression, predominantly as a 0.9 kb transcript. An
interesting feature of the RBM8 transcript is an homology of 42% in the 3'
untranslated region, in the antisense orientation, to the human gonadotropin
releasing hormone receptor polypeptide. RBM8 maps to human chromosome 14 in the
14q21-q23 region.
PMID- 11004517
TI - Sjalpha elements, short interspersed element-like retroposons bearing a
hammerhead ribozyme motif from the genome of the oriental blood fluke Schistosoma
japonicum.
AB - Smalpha is a short interspersed element (SINE)-like retroposon that occurs in
high copy number of the genome of the human blood fluke Schistosoma mansoni. The
sequence of the consensus Smalpha element includes the hallmark features of SINE
like elements including a promoter region for RNA polymerase III, an AT-rich
stretch at its 3'-terminus, a short length of 500 bp or less, and short direct
repeat sequences flanking the insertion site. Interestingly, the sequence of
Smalpha also encodes an active ribozyme bearing a hammerhead domain. Contrary to
the recent findings of Ferbeyre et al. (Mol. Cell. Biol. 18 (1998) 3880-8) that
indicated that Smalpha-like elements were absent from the genome of the Oriental
blood fluke Schistosoma japonicum, we report here that the genome of S. japonicum
does contain a family of Smalpha-like retroposons, elements that we have named
the Sjalpha family. Like Smalpha, Sjalpha elements are SINE-like in structure and
sequence, are present at high copy number interspersed throughout the S.
japonicum genome, and contain an ostensibly functional, hammerhead ribozyme
motif. The presence of these elements in all species of Schistosoma so far
examined suggests that the hammerhead domain was acquired by vertical
transmission from a common schistosome ancestor.
PMID- 11004518
TI - Characterization of mouse cathepsin R, a new member of a family of placentally
expressed cysteine proteases.
AB - A new mouse cysteine protease, termed cathepsin R, has been identified. The
complete nucleotide sequence of this gene was derived from a set of cDNAs
generated from 15.5-day mouse placenta. Sequence analysis revealed an open
reading frame encoding a 334 amino acid long polypeptide closely related to
placentally expressed cathepsins P, Q, and M. RT-PCR analysis indicated that
cathepsin R is only expressed in placenta and thus is a new member of the
emerging family of cathepsins whose expression is regulated during mouse
embryonic development. Modeling and structural analysis suggests that cathepsin R
will have a restricted substrate specificity when compared to that of cathepsin
L.
PMID- 11004519
TI - Mouse connexin37: gene structure and promoter analysis.
AB - Connexin37 (Cx37) is a subunit gap junction protein which exhibits limited
expression in only a few cell types, predominantly in endothelial cells and in
the lung. To begin to analyze Cx37 expression, we isolated a 1.6 kb mouse Cx37
cDNA from a mouse lung cDNA library and isolated corresponding mouse genomic
clones from a bacterial artificial chromosome library. Sequencing and comparison
of these clones showed that the Cx37 gene contained a short first exon, an 1.0 kb
single intron and a second exon containing the complete coding region and 3'
untranslated region (UTR). The 5'-UTR of the mouse cDNA showed 70% identity to
that of human Cx37. Primer extension experiments performed using mouse lung RNA
gave two bands of sizes consistent with the transcription start site predicted
from the cDNA. Sequence analysis showed that the regions flanking exon I
contained a consensus 'TATA box' 43 bp 5' from the transcription start site
preceded by several putative transcription factor binding sites and a 282 bp
truncated L1Md interspersed element. Luciferase reporter gene transfections
suggested that an area of 268 bp 5' from the first exon acted as a basal promoter
for Cx37 and that there was a strong negative regulatory element in the intron.
PMID- 11004520
TI - Identification of a composite enhancer of the human tyrosinase-related protein
2/DOPAchrome tautomerase gene.
AB - The human tyrosinase-related protein 2 (TRP-2) gene promoter contains a cis
regulatory element (positions -447 to -416), termed DOPAchrome tautomerase distal
enhancer 1 (DDE1). DDE1 functions as an enhancer in cultured melanoma cells and
its core element includes a potential binding site for transcription factors
containing a high-mobility-group domain. This core element is bound in vitro by
multiple nuclear proteins, which are preferentially expressed in melanoma cells.
DDE1 represents a composite enhancer that may be involved in melanocyte-specific
transcription of the human TRP-2 gene.
PMID- 11004521
TI - A novel proteinase inhibitor gene transiently induced by tobacco mosaic virus
infection.
AB - A gene (NgPI) encoding a novel proteinase inhibitor (PI) has been isolated from
tobacco leaves. Protein encoded by the gene consists of 241 amino acid residues
having a predicted molecular mass of 26.7 kDa and a calculated pI of 8.7. A
predicted N-terminal signal sequence followed by a vacuolar targeting signal and
a peptide conserved in the Kunitz type PIs were identified. The deduced NgPI
protein has sequence homology with aspartic and cysteine protease inhibitors. The
gene is present as double copies in the Nicotiana glutinosa genome. Expression of
the NgPI gene is rapidly and transiently induced by tobacco mosaic virus
infection at a time earlier than apparent lesions of hypersensitive responses
appear on the leaves.
PMID- 11004522
TI - Cloning and characterization of a novel human ninein protein that interacts with
the glycogen synthase kinase 3beta.
AB - Using human glycogen synthase kinase 3beta (GSK-3beta) as bait in the yeast two
hybrid system, we identified a novel human centrosome associated protein,
hNinein. When the full length cDNA of hNinein was sequenced, it showed that an
open reading frame encoded a protein consisting of 2047 amino acids with a
predicted molecular mass of 239 kDa. The features of this protein include a
potential GTP binding site, a large coiled-coil domain together with four leucine
zipper domains and a GSK-3beta binding site. Fluorescence microscopy experiment
showed that hNinein is localized in the pericentriolar matrix of the centrosome.
In addition, hNinein also showed to react with centrosomal autoantibody sera. Our
findings suggest that hNinein may be involved in the formation of centrosome
matrix and interacts with the GSK-3beta, implying that it may also be regulated
by GSK-3beta phosphorylation signaling.
PMID- 11004523
TI - Cloning of Z39Ig, a novel gene with immunoglobulin-like domains located on human
chromosome X.
AB - The cDNA sequence and expression profile of a novel human gene, encoding a new
member of the immunoglobulin superfamily, is reported. The gene is localized in
the pericentromeric region of human X chromosome between the markers DXS1213 and
DXS1194. Abundant expression of transcripts was detected in several human fetal
tissues, whereas among adult tissues lung and placenta express highest levels of
Z39Ig mRNA.
PMID- 11004524
TI - Molecular cloning of the murine cMOAT ATPase.
AB - cMOAT encodes an ATPase within the family of cMOAT/MRP ATPases that functions as
an ATP dependent, multispecific anion transporter within the canalicular surface
of hepatocytes that has pharmacologic significance. We describe here the cloning
of a murine cMOAT cDNA isolated from mouse liver. The open reading frame of this
cDNA incorporates 4627 nucleotides encoding 1309 amino acids with 77.5% and 86.7%
identity with the human and rat encoded amino acids, respectively. Northern
blotting showed that the expression of cMOAT mRNA occurs primarily in mouse liver
in the form of two variants with approximately 5.6 and 7.8 kb of sequence each.
cMOAT mRNA was also detected in mouse kidney at a low level but was not detected
in other mouse organs or tumors except the Hep 1-6 murine hepatoma where
expression was also in the form of the same two mRNA variants.
PMID- 11004525
TI - Cis element 'decoy' against the upstream promoter of the human estrogen receptor
gene.
AB - It is well known that breast carcinomas without estrogen receptor (ER) have a
poor prognosis and do not respond to endocrine therapy. In analyzing the question
of the lack of ER gene expression, we have considered the possibility that
specific negative transcription factors are present in ER-negative breast
cancers. Inside the P3 upstream promoter of human ER gene we identified a
transcriptional regulatory sequence able to bind protein factors expressed in ER
negative MDA-MB-231 breast cancer cells. This sequence, lying between nucleotides
-3258 to -3157, seems to be critical for inhibition of ER gene transcription. In
fact, the selected sequence in the form of double-stranded DNA has been
introduced into ER-negative breast cancer cells as 'decoy' cis elements showing
the ability to remove the putative negative transcription factor(s) and to induce
the reactivation of ER gene transcription. In addition, in transient transfection
assays the selected sequence decreased the SV-40 promoted luciferase activity.
Gel shift assays identified multiple DNA-protein interactions which specifically
form in this region, and data from Southwestern experiments strongly suggested
the presence of a specific protein expressed in MDA-MB-231 ER-negative, but not
in MCF7 ER-positive cells.
PMID- 11004526
TI - Posttranslational processing and differential glycosylation of Tractin, an Ig
superfamily member involved in regulation of axonal outgrowth.
AB - Tractin is a novel member of the Ig-superfamily which has a highly unusual
structure. It contains six Ig domains, four FNIII-like domains, an acidic domain,
12 repeats of a novel proline- and glycine-rich motif with sequence similarity to
collagen, a transmembrane domain, and an intracellular tail with an ankyrin and a
PDZ domain binding motif. By generating domain-specific antibodies, we show that
Tractin is proteolytically processed at two cleavage sites, one located in the
third FNIII domain, and a second located just proximal to the transmembrane
domain resulting in the formation of four fragments. The most NH(2)-terminal
fragment which is glycosylated with the Lan3-2, Lan4-2, and Laz2-369
glycoepitopes is secreted, and we present evidence which supports a model in
which the remaining fragments combine to form a secreted homodimer as well as a
transmembrane heterodimer. The extracellular domain of the dimers is mostly made
up of the collagen-like PG/YG-repeat domain but also contains 11/2 FNIII domain
and the acidic domain. The collagen-like PG/YG-repeat domain could be selectively
digested by collagenase and we show by yeast two-hybrid analysis that the
intracellular domain of Tractin can interact with ankyrin. Thus, the
transmembrane heterodimer of Tractin constitutes a novel protein domain
configuration where sequence that has properties similar to that of extracellular
matrix molecules is directly linked to the cytoskeleton through interactions with
ankyrin.
PMID- 11004527
TI - Thioxo amino acid pyrrolidides and thiazolidides: new inhibitors of proline
specific peptidases.
AB - Aminopeptidase P (APP), dipeptidyl peptidase II (DP II), dipeptidyl peptidase IV
(DP IV) and prolyl oligopeptidase (POP) are proline specific peptidases. Hence,
they are able to cleave peptide bonds containing the imino acid proline. Amino
acid pyrrolidides (Pyrr) and thiazolidides (Thia) are well-known product analogue
inhibitors of DP IV and POP. For the first time we describe the influence of a
thioxo amide bond, incorporated into these compounds, on the inhibition of the
proline specific peptidases. Taking into account the substrate specificity of
these peptidases, we have synthesized Xaa-psi[CS-N]-Pyrr and Xaa-psi[CS-N]-Thia
of the amino acids Ala, Phe, Val and Ile. The inhibition constants were
determined for the above mentioned proline specific peptidases isolated from
different sources. As a result, the serine proteases DP II, DP IV and POP were
inhibited competitively, whereas metal-dependent APP displayed a linear mixed
type inhibition with inhibition constants up to 10(-4) M. Thioxylation of Xaa
Pyrr and Xaa-Thia led to a slight decrease of inhibition of DP IV and POP
compared to Xaa-Pyrr and Xaa-Thia, though the inhibition constants were still in
the range up to 10(-7) M. As Xaa-Thia exist as two isomers, we investigated
isomer specific inhibition with regard to DP IV. Thus, our studies have revealed
that DP IV was only inhibited by the Z isomer of the Xaa-psi[CS-N]-Thia. For the
first time, Xaa-Pyrr and Xaa-Thia were characterized as inhibitors of DP II with
inhibition constants in the micromolar range. In contrast to DP IV inhibition,
the Xaa-psi[CS-N]-Pyrr and Xaa-psi[CS-N]-Thia have proven to be more potent
inhibitors of DP II than the corresponding Xaa-Pyrr and Xaa-Thia. Thus, these Xaa
psi[CS-N]-Thia are new potent inhibitors especially suitable for DP II with K(i)
values ranging in the upper nanomolar concentration.
PMID- 11004528
TI - Distinct physical and structural properties of the ovine uterine serpin.
AB - Experiments were performed to examine the relationship between the structure and
function of ovine uterine serpin (OvUS). Limited proteolytic digestion of OvUS
caused cleavage of the 55-57 kDa OvUS to a 42 kDa product nearly identical in
molecular weight to a naturally-occurring breakdown product of OvUS. N-terminal
amino acid sequencing and MALDI-MS revealed that, unlike other serpins, OvUS was
preferentially cleaved at about 70 amino acids upstream of the putative reactive
center loop. Analysis of the partially-digested protein by gel filtration
chromatography suggested that the C-terminal fragment of the protein was still
associated under nondenaturing conditions. Partial digestion of OvUS had no
effect on the protein's secondary structure, thermal stability, ability to bind
lymphocytes or pepsin, or inhibitory activity towards pepsin or mitogen-induced
lymphocyte proliferation. In contrast, mild denaturation of OvUS with 0.5 M
guanidine HCl increased thermal stability. Unlike for other serpins, the increase
in thermal stability was lost upon removal of the denaturant. Incubation of OvUS
with 100 fold molar excess of a peptide corresponding to the putative P(14)-P(2)
region of the RCL for 24 h at 37 degrees C to induce binary complex formation had
no effect on its secondary structure and did not alter the biological activity of
the protein. Synthetic peptides corresponding to the putative P(14)-P(2) region
and the P(7)-P(15') region of the RCL were not inhibitory to pepsin activity or
lymphocyte proliferation. Taken together, these results indicate that the
conformation of OvUS is distinct from the prototypical serpin because conditions
that lead to the large-scale conformational change in other serpins such as
antithrombin III and alpha(1)-antitrypsin do not cause similar changes in OvUS.
Moreover, the putative RCL does not seem to contain the activity required to
inhibit lymphocyte proliferation or pepsin activity.
PMID- 11004529
TI - Evidence for alternative binding modes in the interaction of benzylamine
analogues with bovine liver monoamine oxidase B.
AB - The interaction of purified bovine liver MAO B with the benzylamine analogues N,N
dimethylbenzylamine and alpha-methylbenzylamine has been investigated. Both
classes of analogues are competitive inhibitors of benzylamine oxidase activity.
The K(i) values were determined for nine different para-substituted N, N
dimethylbenzylamine analogues. Analysis of the binding affinities demonstrate the
deprotonated forms of the tertiary amines are preferentially bound to MAO B and
the affinity decreases with increasing van der Waals volume of the para
substituent. The correlation for this relation is:Log K(i)=-0.97+/
(0.28)sigma+(0. 75+/-0.11)(0.1xV(w))-4.24+/-(0.16)alpha-Methyl benzylamine
analogues are also found to be competitive inhibitors of MAO B-catalyzed
benzylamine oxidation. Similar K(i) values were determined using either the S or
R stereoisomers. Analysis of the binding affinities of five para-substituted
alpha-methylbenzylamine analogues to MAO B shows the deprotonated form also to be
preferentially bound and the affinity is marginally increased with increasing van
der Waals volume of the para-substituent:Log K(i)=-0.71sigma-(0.32)(0. 1xV(w))
3.50Comparison of these data with that previously published for para-substituted
benzylamine binding to MAO B (Walker and Edmondson, Biochemistry 33 (1994) 7088
7098) demonstrates that these benzylamine analogues exhibit differing modes of
binding to the active site of MAO B. The presence of an electronic substituent
effect in the binding of these two classes of analogues compared with the lack of
an observable electronic effect in the binding of benzylamine to MAO B is
consistent with the proposal that orientation of the benzyl ring of the bound
substrate is responsible for the absence of an electronic substituent effect on
the rate of the reductive half reaction (Miller and Edmondson, Biochemistry 38
(1999) 13670-13683).
PMID- 11004530
TI - Channeling efficiency in the bifunctional methylenetetrahydrofolate
dehydrogenase/cyclohydrolase domain: the effects of site-directed mutagenesis of
NADP binding residues.
AB - The three-dimensional structure of the dehydrogenase-cyclohydrolase bifunctional
domain of the human trifunctional enzyme indicates that Arg-173 and Ser-197 are
within 3 A of the 2'-phosphate of bound NADP. Site-directed mutagenesis confirms
that Arg-173 is essential for efficient binding and cannot be substituted by
lysine. R173A and R173K have detectable dehydrogenase activity, but the K(m)
values for NADP are increased by at least 500-fold. The S197A mutant has a K(m)
for NADP that is only 20-fold higher than wild-type, indicating that it plays a
supporting role. Forward and reverse cyclohydrolase activities of all the mutants
were unchanged, except that the reverse cyclohydrolase activity of mutants that
bind NADP poorly, or lack Ser-197, cannot be stimulated by 2',5'-ADP. The 50%
channeling efficiency in the forward direction is not improved by the addition of
exogenous NADPH and cannot be explained by premature dissociation of the
dinucleotide from the ternary complex. As well, channeling is unaffected in
mutants that exhibit a wide range of dinucleotide binding. Given that
dinucleotide binding is unrelated to substrate channeling efficiency in the D/C
domain, we propose that the difference in forward and reverse channeling
efficiencies can be explained solely by the movement of the methenylH(4)folate
between two overlapping subsites to which it has different binding affinities.
PMID- 11004531
TI - Hydrolysis by plasma kallikrein of fluorogenic peptides derived from prorenin
processing site.
AB - Human plasma kallikrein (HPK) activates plasma prorenin to renin, and the
physiological significance of this activation is still unknown. In this paper we
investigated the efficiency and the cleavage pattern of the hydrolysis by HPK of
the internally quenched fluorescent peptides (qf-peptides) derived from the amino
acid sequence of human prorenin cleavage site. The peptide Abz-F-S-Q-P-M-K-R-L-T
L-G-N-T-T-Q-EDDnp (Abz=ortho-aminobenzoic acid, and EDDnp=N-[2,4-dinitrophenyl]
ethylene diamine), that corresponds to the amino acid sequence P(7) to P(7)' of
human prorenin cleavage site, is hydrolyzed at the correct processing site (R-L
bond) with k(cat)/K(m)=85 mM(-1) s(-1). Alanine was scanned in all positions from
P(5) to P(5)' in order to investigate the substrate specificity requirements of
HPK. The qf-peptides derived from the equivalent segment of rat prorenin, that
has Lys-Lys as basic amino acid pair, and the peptide Abz-NVTSPVQ-EDDnp that
contains the proposed cleavage site of rat prorenin have very low susceptibility
to hydrolysis by rat plasma kallikrein. These data are according to the
previously reported absence of rat plasma prorenin activation by rat plasma
kallikrein (RPK), and with the view that prorenin activation in rat requires
alternative enzymes and/or mechanism. All the obtained peptides described in this
paper were also assayed with bovine trypsin that was taken as a reference
protease because it is commonly used to activate prorenin.
PMID- 11004532
TI - Glutamine synthetase, hemoglobin alpha-chain, and macrophage migration inhibitory
factor binding to amyloid beta-protein: their identification in rat brain by a
novel affinity chromatography and in Alzheimer's disease brain by
immunoprecipitation.
AB - Proteins binding to amyloid beta-protein (Abeta) may modulate the accumulation of
Abeta in Alzheimer's disease (AD) brain. We developed a monomeric Abeta column
for isolation of the proteins binding to Abeta from rat brain. By amino acid
sequence analysis and immunoreactivity with specific antibodies, we identified
three new Abeta-binding proteins, glutamine synthetase, hemoglobin alpha-chain,
and macrophage migration inhibitory factor as well as serum albumin, beta
tubulin, and glyceraldehyde-3-phosphate dehydrogenase already identified as
proteins bound to amyloid beta-protein precursor. In addition, the retained
fraction contained both apolipoprotein E and alpha(1)-antichymotrypsin already
known as Abeta binding proteins. Furthermore, we detected the complexes of these
new binding proteins with Abeta in a soluble fraction of the cerebral cortex of
AD brain by immunoprecipitation. Our results suggest that these binding proteins
also associate with Abeta, leading to the clearance or the accumulation of Abeta
and the neuronal cell damage in human brain.
PMID- 11004533
TI - Role of salt bridge(s) in the binding and photoconversion of bilirubin bound to
high affinity site on human serum albumin.
AB - The role of salt bridge(s) (between epsilon-NH(2) groups of lysine residues of
human serum albumin (HSA) and carboxyl groups of bilirubin) in the binding and
photoconversion of bilirubin bound to high affinity site on HSA was investigated
by covalent modification of approximately 20% internal (buried) lysine residues
of HSA with acetic anhydride, succinic anhydride and O-methylisourea and white
light irradiation of their complexes with bilirubin. The different HSA
derivatives, namely, acetylated HSA (aHSA), succinylated HSA (sHSA) and
guanidinated HSA (gHSA), thus obtained, were found to be homogeneous with respect
to charge and size and characterized in detail in terms of mean residue
ellipticity, Stokes radius, tryptophan fluorescence, bilirubin binding and the
photochemistry of their complexes with bilirubin. All the three derivatives
retained helical contents and molecular size (Stokes radius) similar to HSA
except for sHSA which showed a slight increase in the Stokes radius from 3.56 to
3.64 nm. Further, fluorescence properties of aHSA and sHSA were also found to be
different from HSA and gHSA. Based on difference spectral change, fluorescence
quenching and fluorescence enhancement results of bilirubin bound to HSA and its
derivatives, nearly 46 and 48% reduction in bilirubin binding was observed in the
case of aHSA and sHSA, respectively. Both aHSA and sHSA showed a decrease of 8-
and 10-fold, respectively, in association constant compared to native HSA.
Although the bisignate circular dichroism (CD) spectra of an equimolar (1:1)
bilirubin-HSA complex was retained by all three HSA derivatives, the intensity of
both positive and negative CD Cotton effects decreased significantly in both aHSA
and sHSA. gHSA which retained net charge identical to native HSA, showed little
decrease in bilirubin binding and the intensity of bisignate CD Cotton effects.
The photochemical reaction of bilirubin bound to aHSA and sHSA produced opposite
results to those observed with HSA and gHSA. A brief (2 min) irradiation of an
equimolar complex of bilirubin with both aHSA and sHSA accompanied a rapid shift
(14-15 nm) in the absorption spectrum of the bound pigment towards the blue
region and almost complete elimination of negative CD Cotton effects while only
moderately affecting the magnitude of positive CD Cotton effects. On the other
hand, similar treatment of the complexes of bilirubin with HSA and gHSA did not
show any change in the absorption spectrum, only a slight decrease in the
intensity of both positive and negative CD Cotton effects was observed. The
fluorescence intensity of bilirubin bound to HSA and gHSA was increased upon
irradiation with white light and after 30 min it was nearly twice the value
observed at 0 min irradiation. Interestingly, no change in the fluorescence
intensity of bilirubin bound either to aHSA or sHSA was observed upon
irradiation, even on increasing the duration of irradiation to 1 h. Taken
together, the results on fluorescence quenching, fluorescence enhancement, CD
spectral changes and visible absorption spectroscopy suggest that salt bridge(s)
of the type (-COO(-).(+)H(3)N-) in which the epsilon-NH(2) group(s) contributed
by lysine residues, are not only involved in the enantioselective binding of
bilirubin but also in the stereospecific photoisomerization of bilirubin bound to
a high affinity site on HSA.
PMID- 11004534
TI - Engineering of substrate mimetics as novel-type substrates for glutamic acid
specific endopeptidases: design, synthesis, and application.
AB - This account reports on the development and function of novel substrate mimetics
as artificial substrates for Glu-specific endopeptidases. Firstly, in an
empirical way, various aliphatic and aromatic analogs of the already established
carboxymethyl thioester-substrate mimetics were designed from simple structure
function relationship studies. The specificity of the newly developed substrates
for Staphylococcus aureus V8 protease-catalyzed reactions have been examined by
steady-state hydrolysis kinetic studies. Additionally, these studies were
expanded to the use of the equally Glu-specific endopeptidase from Bacillus
licheniformis (BL-GSE) which can easily be purified from alcalase in high yields.
Finally, the novel substrate mimetics were used as acyl donor components in BL
GSE- and V8 protease-catalyzed model acyl transfer reactions. The results clarify
the newly developed substrate mimetics as efficient acyl donors as well as BL-GSE
as an attractive alternative to V8 protease for enzymatic peptide synthesis.
PMID- 11004535
TI - Expression and characterisation of a highly repetitive peptide derived from a
wheat seed storage protein.
AB - The high molecular weight (HMW) subunit group of wheat seed storage proteins
impart elasticity to wheat doughs and glutens. They consist of three domains: non
repetitive N- and C-terminal domains, which contain cysteine residues for
covalent cross-linking, and a central domain consisting of repeated sequences.
The circular dichroism and infrared (IR) spectra of an intact HMW subunit were
compared with those of a peptide corresponding to the central repetitive domain
expressed in Escherichia coli. This allowed the structure of the central domain
to be studied in the absence of the N- and C-terminal domains and the
contributions of these domains to the structure of the whole protein to be
determined. In solution the peptide showed the presence of beta-turns and
polyproline II-like structure. Variable temperature studies indicated an
equilibrium between these two structures, the polyproline II conformation
predominating at low temperatures and the beta-turn conformation at higher
temperatures. IR in the hydrated solid state also indicated the presence of beta
turns and intermolecular beta-sheet structures. In contrast, spectroscopy of the
whole subunit showed the presence of alpha-helix in the N- and C-terminal
domains. The content of beta-sheet was also higher in the whole subunit,
indicating that the N- and C-terminal domains may promote the formation of
intermolecular beta-sheet structures between the repetitive sequences, perhaps by
aligning the molecules to promote interaction.
PMID- 11004536
TI - PrP(c) mRNA, but not PrP(Sc) is found in the salivary glands of scrapie-infected
sheep.
AB - Transmission studies in transmissible spongiform encephalopathies (TSEs) have
become increasingly important due to the possible transmission of bovine
spongiform encephalopathy to humans resulting in new variant Creutzfeldt-Jacob
disease. The horizontal transmission of scrapie, a TSE of sheep, is poorly
understood. Possible sources of horizontal transmission are the submandibular and
parotid salivary glands. TSEs like natural sheep scrapie are characterized by the
conversion of a normal protease sensitive prion protein, PrP(c), to an abnormal
protease resistant prion protein, PrP(Sc). Since the presence of PrP(Sc) is an
indicator of disease, the salivary glands of scrapie-infected sheep were examined
for the presence of PrP(Sc). Although PrP(c) mRNA was detected in the salivary
glands, PrP(Sc) was not found in the salivary glands of scrapie-infected sheep.
These data suggest that the salivary glands are unlikely sources of horizontal
transmission of natural sheep scrapie.
PMID- 11004537
TI - A new alternative method to quantify residual structure in 'unfolded' proteins.
AB - Pig (pCSD1) and human (hCSD1) calpastatin domain 1 proteins were studied to
characterize common features of the denatured state of proteins. These proteins
were chosen for the present investigation, because pCSD1 was suggested previously
to be unstructured in water even at 25 degrees C (1) [T. Konno et al., Biochim.
Biophys. Acta 1342 (1997) 73-82]. hCSD1 could be expected to exhibit similar
features on the basis of preliminary spectroscopic studies. In the present study,
the experimental grounds for the estimate of residual structure in the unfolded
state were differential scanning calorimetry heat capacity and circular dichroism
(CD) measurements over the temperature range 10-80 degrees C. At selected
temperatures, we studied also the effect of guanidinium hydrochloride (GdnHCl)
which is known to promote further unfolding of the polypeptide chain. All other
measurements were performed at pH 6 in pure water. The present results support
the conclusion that the comparison of the experimentally obtained heat capacity
data with theoretical heat capacity values calculated on the basis of a newly
established increment system gives insight into the degree of hydration of the
unfolded polypeptide chain. The percentage by which the experimental heat
capacity of the unfolded polypeptide chain differs from the calculated heat
capacity permits a quantitative estimate of the residual structure. This estimate
is in good agreement with that based on CD absorption. The heat capacity approach
has the advantage of comparing fully hydrated and partially hydrated residues in
the same aqueous environment, whereas for example spectroscopic measurements,
such as CD, are generally referred to the fully unfolded chain in concentrated
urea or GdnHCl solutions. As the unfolded chains of pCSD1 and hCSD1 exhibit a
smaller heat capacity than that calculated on the new peptide-based increment
system [M. Hackel et al., J. Mol. Biol. 291 (1999) 197-213], we conclude that the
residues in the unfolded polypeptide chain are less hydrated than the same
residues in oligopeptides. This suboptimal hydration is the result of residual
structure in the chain as observed in both CD and heat capacity measurements.
PMID- 11004538
TI - Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase: pre
steady-state kinetic studies.
AB - Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase (DMAPP
tRNA transferase) catalyzes the first step in the biosynthesis of the
hypermodified A37 residue in tRNAs that read codons beginning with uridine. The
mechanism of the enzyme-catalyzed reaction was studied by isotope trapping, pre
steady-state rapid quench, and single turnover experiments. Isotope trapping
indicated that the enzyme.tRNA complex is catalytically competent, whereas the
enzyme.DMAPP complex is not. The results are consistent with an ordered
sequential mechanism for substrate binding where tRNA binds first. The
association and dissociation rate constants for the enzyme.tRNA binary complex
are 1. 15+/-0.33x10(7) M(-1) s(-1) and 0.06+/-0.01 s(-1), respectively. Addition
of DMAPP gives an enzyme.tRNA.DMAPP ternary complex in rapid equilibrium with the
binary complex and DMAPP. Rapid quench studies yielded a linear profile
(k(cat)=0.36+/-0.01 s(-1)) with no evidence for buildup of enzyme-bound product.
Product release from DMAPP-tRNA transferase is therefore not rate-limiting. The
Michaelis constant for tRNA and the equilibrium dissociation constant for DMAPP
calculated from the individual rate constants determined here are consistent with
values obtained from a steady-state kinetic analysis.
PMID- 11004539
TI - Arrangement of functional units within the Rapana thomasiana hemocyanin subunit
RtH2.
AB - For the determination of the number and linear sequential arrangement of
functional units (FUs) within the polypeptide chain of the Rapana hemocyanin
subunit RtH2, a panel of mono-, di-, tri- and penta-FU fragments was generated by
limited proteolysis of the purified subunit with four different enzymes. The
individual cleavage products were isolated, characterized by SDS-PAGE and N
terminally sequenced. Most of the information about the FU sequential arrangement
within RtH2 was obtained after limited proteolysis of the subunit with plasmin.
Overall correlation of the data revealed the sequential order of the eight FUs
within the polypeptide chain of RtH2, termed RtH2-a to RtH2-h. The sites, most
sensitive to proteolytic cleavage with plasmin, are located at the C-terminus,
between the FUs ef, fg and gh. A second main cleavage site was observed between
the FUs cd. Endoproteinase GluC hydrolyzes these sites, too, but produces
exclusively a mixture of mono-, di- and tri-FU fragments. The most stable
fragments, the trimer abc and the dimer gh, are found in all cleavage mixtures of
RtH2 studied. RtH2-h is compared with the corresponding h-FUs of the gastropodan
hemocyanins of Pila leopoldvillensis, Helix pomatia, Megathura crenulata and
Haliotis tuberculata, and a remarkable similarity is observed between them: an
increased M(r) of approximately 65000 instead of approximately 50000, estimated
for an average FU, suggesting that the sequence of RtH2-h is elongated by about
95 amino acid residues at the C-terminal part of the molecule, as found for
beta(c)-HpH, HtH1 and HtH2.
PMID- 11004540
TI - Kinetic and hydrodynamic studies of the NodL O-acetyl transferase of Rhizobium
leguminosarum: a random-order ternary complex mechanism for acetyl transfer by a
roughly spherical trimeric protein.
AB - The nodL gene product of Rhizobium leguminosarum is required for O-acetylation of
diffusible lipo-oligosaccharide signalling factors which are involved in the host
specific nodulation of legume roots. Kinetic studies of the forward reaction,
using the substrate analogues chitosan pentaose and chitosan tetraose and the
acyl donors acetyl-CoA and propionyl-CoA, and the dead-end inhibitor EtCoA are
consistent with a steady-state random-order ternary complex mechanism in which
the off rate of the O-acetyl chitosan oligomer appears to be partially rate
determining. Moreover, the linearity of primary double-reciprocal plots favours
the view that the interconversion of the ternary complex of NodL and its
substrates with that of enzyme and bound products is not significantly faster
than k(cat). Dissociation constants for coenzyme A and acetyl-CoA were determined
by titration microcalorimetry to be 16.5 and 7.2 microM respectively, the latter
in agreement with the kinetically derived value of 7.0 microM. The physical state
of purified NodL, as determined by equilibrium centrifugation, velocity
sedimentation and quasi-elastic light scattering, is that of a roughly spherical,
trimeric protein with little tendency to self-associate.
PMID- 11004541
TI - Conformational correlation and coupled motion between residue A21 and B25 side
chain observed in crystal structures of insulin mutants at position A21.
AB - The C-terminal residue of the insulin A chain is invariant and kept as asparagine
in all known insulin molecules from hagfish through birds to mammals. To get
information on the role of this conserved residue, which is still unclear, the
three-dimensional structures of four human insulin mutants, A21 Asn-->Gly, A21
Asn-->Asp, A21 Asn-->Ala, and A21 Asn-->Gln DesB30, were determined by X-ray
crystallography. The four mutants crystallize separately into two kinds
(rhombohedral and cubic) of crystals. In the refined structures, conformational
correlation and coupled motion between the A chain C-terminal residue A21 and the
B25 side chain was observed, in contrast to the nearly unchanged general
structures as compared with the native insulin structures in their respective
crystals. A detailed analysis suggests that residue A21 can affect insulin
receptor binding by interaction with the B25 side chain and the B chain C
terminal segment to assist the B25 side chain rearranging into the 'active'
conformation.
PMID- 11004542
TI - Calcium-induced flexibility changes in the troponin C-troponin I complex.
AB - The contraction of vertebrate striated muscle is modulated by Ca(2+) binding to
the regulatory protein troponin C (TnC). Ca(2+) binding causes conformational
changes in TnC which alter its interaction with the inhibitory protein troponin I
(TnI), initiating the regulatory process. We have used the frequency domain
method of fluorescence resonance energy transfer (FRET) to measure distances and
distance distributions between specific sites in the TnC-TnI complex in the
presence and absence of Ca(2+) or Mg(2+). Using sequences based on rabbit
skeletal muscle proteins, we prepared functional, binary complexes of wild-type
TnC and a TnI mutant which contains no Cys residues and a single Trp residue at
position 106 within the TnI inhibitory region. We used TnI Trp-106 as the FRET
donor, and we introduced energy acceptor groups into TnC by labeling at Met-25
with dansyl aziridine or at Cys-98 with N-(iodoacetyl)-N'-(1-sulfo-5
naphthyl)ethylenediamine. Our distance distribution measurements indicate that
the TnC-TnI complex is relatively rigid in the absence of Ca(2+), but becomes
much more flexible when Ca(2+) binds to regulatory sites in TnC. This increased
flexibility may be propagated to the whole thin filament, helping to release the
inhibition of actomyosin ATPase activity and allowing the muscle to contract.
This is the first report of distance distributions between TnC and TnI in their
binary complex.
PMID- 11004543
TI - Effect of pH on the structure and aggregation of human glycodelin A. A comparison
with beta-lactoglobulin A.
AB - The effect of pH on the structure of glycodelin A (GdA) and of beta-lactoglobulin
A (beta-LgA) has been investigated by means of circular dichroism, steady state
fluorescence, synchrotron radiation small angle X-ray scattering (SR-SAXS) and
gel permeation chromatography. The comparison between GdA and beta-LgA shows
that, at pH 7.0, both proteins are dimers with an extended content of beta-sheet
conformation, but pH 2.0 and 9.0 yield a different secondary, tertiary and
quaternary structural organisation. Whilst beta-LgA is a monomer, that conserves
beta-sheet conformation at pH 2.0 and 9.0, GdA has a stable dimeric structure at
alkaline pH, but at pH 2.0 increases its alpha-helix content and it aggregates
soon. SR beam has been used to perform SAXS comparative measurements of the two
proteins. SR-SAXS data provide the radius of gyration and the radii of the cross
section and of the thickness. GdA aggregation at acid pH has been characterised
by calculating the distance distribution function (P(r)). Isoelectric focusing
and chromatofocusing data show a different charge distribution on the surfaces of
the two proteins, supporting the hypothesis that the presence of oligosaccharides
deeply influences the conformational state and the aggregation process of GdA at
different pH values. In particular, the presence of sialic acid residues, within
the oligosaccharide moiety of the GdA, might be responsible for the differences
observed between the two proteins.
PMID- 11004544
TI - Purification, physico-chemical characterization and sequence of a heat labile
alkaline metalloprotease isolated from a psychrophilic Pseudomonas species.
AB - The psychrophilic alkaline metalloprotease (PAP) produced by a Pseudomonas
bacterium isolated from Antarctica has been purified and characterized. The gene
encoding PAP has been cloned and sequenced and the derived amino acid sequence
shows 66% identity with the mesophilic alkaline metalloprotease from Pseudomonas
aeruginosa IFO 3455 (AP). Compared to the purified AP, PAP is three times more
active at 20 degrees C, is very sensitive to chelating agents and is rapidly
inactivated at 45 degrees C. The lower thermostability of PAP can tentatively be
explained by a loss of a stabilizing Ca(2+), a decrease in the content of
hydrophobic residues and a smaller aliphatic index.
PMID- 11004545
TI - Conformational study of a custom antibacterial peptide cecropin B1: implications
of the lytic activity.
AB - Cecropin B1 (CB1) with two amphipathic alpha-helical segments is a derivative of
the natural antibacterial peptide, cecropin B. The assays of cell lysis show
that, compared with cecropin A (CA), CB1 has a similar ability to lyse bacteria
with a higher potency (two- to six-fold higher) in killing cancer cells. The
difference may be due to the fact that the peptides possess different structures
and sequences. In this study, the solution structure of CB1 in 20%
hexafluoroisopropanol was determined by two-dimensional nuclear magnetic
resonance (NMR) spectroscopy. The (1)H NMR resonances were assigned. A total of
350 inter-proton distances were used to calculate the solution structure of CB1.
The final ensemble structures were well converged, showing the minimum root mean
square deviation. The results indicate that CB1 has two stretches of helices
spanning from residues 3 to 22 and from residues 26 to 33, which are connected by
a hinge section formed by Gly-23 and Pro-24. Lys-25 is partially incorporated in
the hinge region. The bent angle between two helical segments located in two
planes was between 100 and 110 degrees. With comparisons of the known NMR
structure of CA and its activities on bacteria and cancer cells, the structure
function relationship of the peptides is discussed.
PMID- 11004546
TI - Stoichiometry and inter-subunit interaction of the wedge initiation complex, gp10
gp11, of bacteriophage T4.
AB - Association of gp10 and gp11 (gp=gene product) is the first step in the assembly
pathway of the wedge part of the baseplate of bacteriophage T4. The gp10-gp11
complex constitutes the six tail pins at the corners of the baseplate hexagon on
the distal side. The stoichiometry of the subunits, gp10 and gp11, of this
complex was determined in combination with sedimentation equilibrium, Edman
degradation of the complex and sodium dodecylsulfate-polyacrylamide gel
electrophoresis (SDS-PAGE). From the results of Edman degradation and SDS-PAGE,
the molar ratio of gp10 and gp11 was approximately 1. On the other hand, the
molecular weight of the purified gp10-gp11 complex was determined by
sedimentation equilibrium to be 284000+/-7000, which is in good agreement with
the expected value of 269840 if the stoichiometry is 3:3. Furthermore, comparison
of the results in the presence and in the absence of reducing reagent, 2
mercaptoethanol (2-ME), in SDS-PAGE revealed that two molecules of gp10 in the
complex formed a disulfide bond, while the third gp10 molecule does not
participate in the disulfide bond formation.
PMID- 11004547
TI - A catalytic site of protein disulfide isomerase probed with adenosine-5'
triphosphate analogs.
AB - Anthraniloyl adenosine-5'-triphosphate (Ant-ATP) and etheno-adenosine-5'
triphosphate (epsilon-ATP) complexed to Mg(2+) ions are substrates of protein
disulfide isomerase (PDI). epsilon-ATP, coordinated to Tb(3+) ions, was used as a
probe of the ATPase binding site. Sensitized luminescence arising from resonance
energy transfer from epsilon-adenine to Tb(3+) is quenched by PDI. The
luminescence results are discussed in reference to a model in which the distance
of separation between epsilon-adenine (donor) and Tb(3+) (acceptor) is increased
upon binding of PDI. The interaction of a small peptide of 14 amino acid residues
with the b/b' domain of the protein does not influence the ATPase activity. The
phosphorescence, fluorescence and fluorescence anisotropy of bound epsilon-ATP
are not perturbed by the binding of the small molecular weight peptide to PDI. It
is suggested that the peptide and ATP do not share a common binding site on the
b/b' domain.
PMID- 11004548
TI - Quantitative characterization of homo- and heteroassociations of muscle
phosphofructokinase with aldolase.
AB - Dissociation of purified phosphofructokinase accompanied with inactivation was
analyzed in the absence and presence of aldolase and the data were compared with
those obtained with muscle extract. The kinetics of the decrease in enzymatic
activity was highly dependent on the dilution factor in both cases, but the
inactivation appeared to be biphasic only with extract. The inactivation of the
phosphofructokinase was impeded by addition of excess of aldolase. Time courses
of kinase inactivation were fitted by alternative kinetic models to characterize
the multiple equilibria of several homo- and hetero-oligomers of
phosphofructokinase. The combination of modeling data obtained with purified and
extract systems suggests that aldolase binds to an intermediate dimer of
phosphofructokinase and within this heterocomplex the kinase is completely
active. The intermediate dimer is stabilized by association with microtubules and
the kinase activity decreased due to dilution can be recovered by addition of
excess aldolase. In extract, the phosphofructokinase is of sigmoidal character
(Hill coefficient of 2.3); the addition of excess exogenous aldolase to
phosphofructokinase resulted in heterocomplex formation displaying Michaelian
kinetics. The possible physiological relevance of heterocomplex formation of
phosphofructokinase in muscle extract is discussed.
PMID- 11004549
TI - The adhesive protein of Choromytilus chorus (Molina, 1782) and Aulacomya ater
(Molina, 1782): a proline-rich and a glycine-rich polyphenolic protein.
AB - The adhesive polyphenolic proteins from Aulacomya ater and Choromytilus chorus
with apparent molecular masses of 135000 and 105000, respectively, were digested
with trypsin and the peptides produced resolved by reversed phase liquid
chromatography. About 5 and 12 major peptides were obtained from the protein of
A. ater and C. chorus, respectively. The major peptides were purified by reverse
phase chromatography and the amino acid sequence indicates that both polyphenolic
proteins consisted of repeated sequence motifs in their primary structure. The
major peptides of A. ater contain seven amino acids corresponding to the
consensus sequence AGYGGXK, whereas the tyrosine was always found as 3, 4
dihydroxyphenylalanine (Dopa), the X residue in position 6 was either valine,
leucine or isoleucine, and the carboxy terminal was either lysine or
hydroxylysine. On the other hand, the major peptides of C. chorus ranged in size
from 6 to 21 amino acids and the majority correspond to the consensus sequence
AKPSKYPTGYKPPVK. Both proteins differ markedly in the sequence of their tryptic
peptides, but they share the common characteristics of other adhesive proteins in
having a tandem sequence repeat in their primary structure.
PMID- 11004550
TI - Thermochemistry of the specific binding of C12 surfactants to bovine serum
albumin.
AB - The specific binding to bovine serum albumin (BSA) of anionic and non-ionic
surfactants with C12 acyl chains has been studied by high sensitivity isothermal
titration calorimetry. This method proved particularly effective in resolving the
binding of anionic surfactants into separate classes of sites with different
affinity. For sodium dodecylsulfate (SDS) the measured binding curves could be
rationalized as association to two classes (high affinity/low affinity) of sites
comprising, respectively, three and six similar (i.e. thermodynamically
equivalent), independent sites. Changes in the thermodynamic functions enthalpy,
standard free energy, standard entropy and heat capacity could be discerned for
each class of binding site, as well as for micelle formation. These data suggest
that binding to low affinity sites (in analogy with micelle formation) exhibits
energetic parameters; in particular, a large negative change in heat capacity,
which is characteristic of hydrophobic interactions. The thermodynamics of high
affinity binding, on the other hand, is indicative of other dominant forces; most
likely electrostatic interactions. Other anionic ligands investigated (laurate
and dodecyl benzylsulfonate) showed a behavior similar to SDS, the most
significant difference being the high affinity binding of the alkylbenzyl
sulfonate. For this ligand, the thermodynamic data is indicative of a more
loosely associated complex than for SDS and laurate. BSA was found to bind one or
two of the non-ionic surfactants (NIS) hepta- or penta(ethylene glycol)
monododecyl ether (C12EO7 and C12EO5) with binding constants about three orders
of magnitude lower than for SDS. Hence, the free energy of the surfactant in the
weakly bound BSA-NIS complex is only slightly favored over the micellar state.
The binding process is characterized by very large exothermic enthalpy changes
(larger than for the charged surfactants) and a large, positive increment in heat
capacity. These observations cannot be reconciled with a molecular picture based
on simple hydrophobic condensation onto non-polar patches on the protein surface.
PMID- 11004551
TI - Effect of P(2)' site tryptophan and P(20)' site deletion of Momordica charantia
trypsin inhibitor II on inhibition of proteinases.
AB - Momordica charantia trypsin inhibitor II (MCTI-II) inhibits the amidolytic
activity of factor Xa with a K(i) value 10-100-fold smaller than those of other
squash family inhibitors. It also inhibits factor X activation mediated by factor
VIIa-tissue factor complex or factor IXa. Comparison of other squash family
inhibitors reveal Trp at position 7 (P(2)') and a deletion at position 25
(P(20)') are characteristics of MCTI-II. In order to elucidate the effect of
these positions on the inhibitory activity, we chemically synthesized three
inhibitors: S-MCTI-II whose amino acid sequence is identical to natural MCTI-II,
S-MCTI-II(7L) whose P(2)'(Trp) is substituted with Leu, and S-MCTI-II(25N) whose
P(20)'(deletion) is filled with Asn. The dissociation constants of the complexes
of human factor Xa with S-MCTI-II, S-MCTI-II(7L), and S-MCTI-II(25N) were 1.3x10(
6) M, 2.8x10(-5) M, and 7.3x10(-6) M, respectively. They inhibited factor X
activation mediated by factor VIIa with the same degree. As in the case of
natural MCTI-II, S-MCTI-II suppressed factor X activation mediated by factor IXa,
while S-MCTI-II(7L) and S-MCTI-II(25N) did not. Both the Trp at the P(2)'
position and deletion at the P(20)' position are thus likely required for the
inhibition of factor Xa, trypsin, and factor IXa, while these two positions do
not affect factor X activation initiated by the factor VIIa-tissue factor
complex.
PMID- 11004552
TI - pH-induced domain interaction and conformational transitions of lipoxygenase-1.
AB - The multidomain structure of soybean LOX1 was examined over the pH range 1-12.
Lipoxygenase-1 activity was reversible over broad pH range of 4-10 due to the
reversibility of conformational states of the molecule. Below pH 4.0, due to
collapse in hydrophobic interactions, the enzyme unfolded to an irreversible
conformation with the properties of molten globule state with a mid point of
transition at pH 2.4. This intermediate state lost iron irreversibly. In alkaline
pH at 11.5, LOX1 underwent partial unfolding with the exposure of cysteine
residues with subsequent oxidation of a pair of cysteine residues in the C
terminal domain and this intermediate showed some properties of molten globule
state and retained 35% of activity. Beyond pH 12.0, the enzyme was completely
inactivated irreversibly due to irreversible conformational changes. The pH
dependent urea-induced unfolding of LOX1 suggested that LOX1 was more stable at
pH 7.0 and least stable at pH 9.0. Furthermore, the urea-induced unfolding of
LOX1 indicated that the unfolding was biphasic due to pH-dependent domain
interactions and involved sequential unfolding of domains. The loss of enzyme
activity at pH 4. 0 and 7.0 occurred much earlier to unfolding of the C-domain at
all pHs studied. The combination of urea-induced unfolding measurements and
limited proteolysis experiments suggested that at pH 4.0, the domains in LOX1
were less interactive and existed as tightly folded units. Furthermore, these
results confirmed the contribution of ionic interactions in the interdomain
contacts.
PMID- 11004553
TI - Arginine to citrulline replacement in substrates of phosphorylase kinase.
AB - Synthetic peptides based on residues 9 to 18 of glycogen phosphorylase were
prepared containing citrulline at position 10 or 16, or at both positions 10 and
16. The peptides were compared as substrates for a recombinant, truncated form of
the catalytic subunit of phosphorylase kinase (residues 1-300). The peptide
having citrulline at position 10 was phosphorylated the same as the parent
peptide. Both the peptides with a single citrulline at position 16 and with two
citrullines were phosphorylated less effectively than the parent peptide;
k(cat)/K(m) values were approximately 20% the value with the parent peptide.
Incorporation of the second citrulline had little change in the effectiveness of
the peptide as a substrate although the kinetic parameters with the citrulline
peptides did show differences. The change in peptide phosphorylation did not seem
to result from a change in peptide structure. Two-dimensional nuclear magnetic
resonance studies of di-citrulline peptide are reported and showed no change in
the solution structure of the peptide compared to the parent peptide. Thus, the
change in kinetic parameters with the modified peptides seemed an effect of
arginine replacement and was likely a consequence of the loss of charge inasmuch
as the size of arginine and citrulline are similar. Arginine-16 was concluded to
be more important for phosphorylase kinase recognition than arginine-10. These
findings were consistent with the earlier studies using alanine replacement of
arginine in synthetic peptides as substrates for the holoenzyme form of
phosphorylase kinase.
PMID- 11004554
TI - Structure and function of alpha-fetoprotein: a biophysical overview.
AB - alpha-Fetoprotein (AFP) is a large serum glycoprotein belonging to the intriguing
class of onco-developmental proteins. AFP has attracted considerable attention
since it was shown that the change in its serum level during pregnancy is a
hallmark of the development of numerous embryonic disorders, while the increase
in its content in the plasma of adults correlates with the appearance of several
pathological conditions. Over the past 30 years, some 11000 papers have been
published concerning AFP, an average rate of over a publication a day since 1969.
The majority of publications are about the application of the protein in
diagnostics, or about other uses of AFP in biomedicine; though some of them
describe the biochemical and functional properties of AFP, two aspects have been
extensively reviewed. However, surprisingly little is currently known about
structural properties of this protein as well as about the molecular mechanism of
its function. The present review pursues the aim to describe the current state of
the art in studies of structural properties and conformational stability of AFP.
An attempt to establish the relationship between conformational transformations
in AFP and its function is also made.
PMID- 11004555
TI - Structural changes in cytochrome c oxidase induced by cytochrome c binding. A
resonance raman study.
AB - Electrostatically stabilized complexes of fully oxidized cytochrome c oxidase
from Paracoccus denitrificans and horse heart cytochrome c were studied by
resonance Raman spectroscopy. The experiments were carried out with the wild-type
oxidase and a variant in which a negatively charged amino acid in the binding
domain (D257) is replaced by an asparagine. It is shown that cytochrome c induces
structural changes at heme a and heme a(3) which are reminiscent to those found
in mammalian cytochrome c oxidase-cytochrome c complex. The spectral changes are
attributed to subtle changes in the heme-protein interactions implying that there
is a structural communication from the binding domain even to the remote
catalytic center. Only for the heme a modes minor spectral differences were found
in the response of the wild-type and the D257N variant oxidase upon cytochrome c
binding indicating that electrostatic interactions of aspartate 257 are not
crucial for the perturbation of the catalytic site structure in the complex. On
the other hand, in none of the complexes, structural changes were detected in the
bound cytochrome c. These findings are in contrast to previous results obtained
with beef heart cytochrome c oxidase which triggers the formation of a new
conformational state of cytochrome c assumed to be involved in the biological
electron transfer process.
PMID- 11004556
TI - Characterisation of two protein phosphatase 2A holoenzymes from maize seedlings.
AB - Two holoenzymes of protein phosphatase 2A (PP2A), designated PP2AI and PP2AII,
were purified from maize seedlings. The subunit composition of maize holoenzymes
generally resembled those of animal PP2A. Using SDS/PAGE and Western blots with
antibodies generated against peptides derived from animal PP2A, we established
the subunit composition of plant protein phosphatase 2A. In both maize
holoenzymes, a 38000 catalytic (PP2Ac) and a 66000 constant regulatory subunit
(A) constituting the core dimer of PP2A were present. In addition, PP2AI (180000
200000) contained a protein of 57000 which reacted with antibodies generated
against the peptide (EFDYLKSLEIEE) conserved in all eukaryotic Balpha regulatory
subunits. In contrast, none of the proteins visualised in PP2AII (140000-160000)
by double staining reacted with these antibodies. The activity of PP2AI measured
with (32)P-labelled phosphorylase a in the presence of protamine and ammonium
sulfate is about two times higher than that of PP2AII. PP2AI and PP2AII displayed
different patterns of activation by protamine, polylysine and histone H1 and
exhibit high sensitivity toward inhibition by okadaic acid. The data obtained
provide direct biochemical evidence for the existence in plants of PP2A
holoenzymes composed of a catalytic subunit complexed with one or two regulatory
subunits.
PMID- 11004557
TI - Is cellobiose dehydrogenase from Phanerochaete chrysosporium a lignin degrading
enzyme?
AB - Cellobiose dehydrogenase (CDH) is an extracellular redox enzyme of ping-pong
type, i.e. it has separate oxidative and reductive half reactions. Several wood
degrading fungi produce CDH, but the biological function of the enzyme is not
known with certainty. It can, however, indirectly generate hydroxyl radicals by
reducing Fe(3+) to Fe(2+) and O2 to H2O2. Hydroxyl radicals are then generated by
a Fenton type reaction and they can react with various wood compounds, including
lignin. In this work we study the effect of CDH on a non-phenolic lignin model
compound (3,4-dimethoxyphenyl glycol). The results indicate that CDH can affect
lignins in three important ways. (1) It breaks beta-ethers; (2) it demethoxylates
aromatic structures in lignins; (3) it introduces hydroxyl groups in non-phenolic
lignins. The gamma-irradiated model compound gave a similar pattern of products
as the CDH treated model compound, when the samples were analyzed by HPLC,
suggesting that hydroxyl radicals are the active component of the CDH system.
PMID- 11004558
TI - Effects of ionic surfactants used in reversed micelles on cutinase activity and
stability.
AB - The effects of aqueous surfactant solutions on the kinetics and stability of
cutinase from Fusarium solani pisi were studied. The surfactant sodium bis[2
ethylhexyl]ester sulfosuccinic acid (AOT) acts as a pseudo-competitive inhibitor
within a limited concentration range relative to the hydrolysis of short-chain p
nitrophenyl esters. For higher concentrations a hyperbolic mixed inhibition takes
place. A pseudo-activation of hydrolysis in presence of AOT and
hexadecyltrimethyl-ammonium bromide (CTAB) was observed. CTAB has similar effects
on kinetics of cutinase. Cutinase revealed to be stable in CTAB solutions, with
activity retention as high as 80%. AOT has a deleterious effect on the enzyme in
the time course, resulting in acute loss of activity possibly related with
unfolding of the protein structure. A relation between deactivation rate
constants and AOT/cutinase concentration ratios is suggested. The presence of the
linear alcohol, 1-hexanol, was included in these solutions, in the attempt to
interpret the deactivation of cutinase when encapsulated in reversed micelle
systems in the absence of this co-surfactant.
PMID- 11004559
TI - Enzymic characteristics of secreted aspartic proteases of Candida albicans.
AB - Candida yeasts are rarely infectious, but frequently cause life-threatening
systemic infections in patients immunocompromised by AIDS or by immunosuppressive
therapeutics. The secreted aspartic proteases (Saps) are known virulence factors
of pernicious Candida species. The most virulent, Candida albicans, possesses at
least nine SAP genes, some of which are specifically expressed from cells with
morphologies associated with virulence. Only one of these proteases, Sap2, has
been previously purified from yeast in sufficient quantities for enzymic studies.
The other enzymes are present in low amounts in yeast culture and are difficult
to purify. As a consequence, enzyme properties, including the substrate
specificities, of all Saps are poorly studied. Therefore, four Saps that are
known to be expressed in C. albicans, Sap1, Sap2, Sap3 and Sap6, were produced in
Escherichia coli as recombinant zymogens and purified in large quantities. These
proenzymes were autoactivated and purified as active proteases. The enzymic
properties including the substrate specificities at the P(1) and P(1)' sites were
determined using a competitive hydrolysis method employing synthetic substrate
mixtures. All four Saps cleave peptide bonds between larger hydrophobic amino
acids, but these somewhat broad specificities differ in detail among the four
enzymes at both sites. At the P(1) site, Sap1, Sap2 and Sap6 prefer Phe while
Sap3 prefers Leu. Positively charged amino acids are also accommodated,
especially by Sap2 and Sap3. The specificities at P(1)' are broader than at P(1)
for all four enzymes. Sap6 prefers Ala, whereas other Saps prefer Tyr. Acidic
side chains are also accommodated at this site. Analysis of substrates with a
hydrophobic amino acid in P(1)' reveals that all the Saps possess a unique
preference for Ala at this site. The observed differences of residue preferences
among Saps may be utilized for the design of specific substrates and inhibitors.
PMID- 11004560
TI - Specificity of DNA binding and methylation by the M.FokI DNA methyltransferase.
AB - The M.FokI adenine-N(6) DNA methyltransferase recognizes the asymmetric DNA
sequence GGATG/CATCC. It consists of two domains each containing all motifs
characteristic for adenine-N(6) DNA methyltransferases. We have studied the
specificity of DNA-methylation by both domains using 27 hemimethylated
oligonucleotide substrates containing recognition sites which differ in one or
two base pairs from GGATG or CATCC. The N-terminal domain of M.FokI interacts
very specifically with GGATG-sequences, because only one of the altered sites is
modified. In contrast, the C-terminal domain shows lower specificity. It prefers
CATCC-sequences but only two of the 12 star sites (i.e. sites that differ in 1 bp
from the recognition site) are not accepted and some star sites are modified with
rates reduced only 2-3-fold. In addition, GGATGC- and CGATGC-sites are modified
which differ at two positions from CATCC. DNA binding experiments show that the N
terminal domain preferentially binds to hemimethylated GGATG/C(m)ATCC sequences
whereas the C-terminal domain binds to DNA with higher affinity but without
specificity. Protein-protein interaction assays show that both domains of M.FokI
are in contact with each other. However, several DNA-binding experiments
demonstrate that DNA-binding of both domains is mutually exclusive in full-length
M.FokI and both domains do not functionally influence each other. The
implications of these results on the molecular evolution of type IIS
restriction/modification systems are discussed.
PMID- 11004561
TI - Characterization of yeast seryl-tRNA synthetase active site mutants with improved
discrimination against substrate analogues.
AB - The involvement of amino acids within the motif 2 loop of Saccharomyces
cerevisiae seryl-tRNA synthetase (SerRS) in serine and ATP binding was
demonstrated previously [B. Lenhard et al., J. Biol. Chem. 272 (1997) 1136-1141].
In our attempt to analyze the structural basis for the substrate specificity and
to explore further the catalytic mechanism employed by S. cerevisiae SerRS, two
new active site mutants, SerRS11 and SerRS12, were constructed. The catalytic
effects of amino acid replacement at positions Lys287, Asp288 and Ala289 with
purified wild-type and mutant seryl-tRNA synthetases were tested. The alteration
of these semi-conserved amino acids interferes with tRNA-dependent optimization
of serine recognition. Additionally, mutated enzymes SerRS11 (Lys287Thr,
Asp288Tyr, Ala289Val) and SerRS12 (Lys287Arg) are less sensitive to inhibition by
two competitive inhibitors: serine hydroxamate, an analogue of serine, and 5'-O
[N-(L-seryl)-sulfamoyl]adenosine, a stable analogue of aminoacyl adenylate, than
the wild-type enzyme. SerRS mutants also display different activation kinetics
for serine and serine hydroxamate, indicating that specificity toward the
substrates is modulated by amino acid replacement in the motif 2 loop.
PMID- 11004562
TI - The K(+) affinity of gastric H(+),K(+)-ATPase is affected by both lipid
composition and the beta-subunit.
AB - It is generally assumed that negatively charged residues present in the alpha
subunit of gastric H(+),K(+)-ATPase are involved in K(+) binding and transport.
Despite the fact that there is no difference between various species regarding
these negatively charged residues, it was observed that the apparent K(+)
affinity of the pig enzyme was much lower than that of the rat H(+),K(+)-ATPase.
By determining the K(+)-stimulated dephosphorylation reaction of the
phosphorylated intermediate K(0.5) values for K(+) of 0.12+/-0.01 and 1.73+/-0.03
mM were obtained (ratio 14.4) for the rat and the pig enzyme, respectively. To
investigate the reason for the observed difference in K(+) sensitivity, both
enzymes originating from the gastric mucosa were either reconstituted in a
similar lipid environment or expressed in Sf9 cells. After reconstitution in K(+)
permeable phosphatidylcholine/cholesterol liposomes K(0.5) values for K(+) of
0.16+/-0.01 and 0.35+/-0.05 mM for the rat and pig enzyme respectively were
measured (ratio 2.2). After expression in Sf9 cells the pig gastric H(+),K(+)
ATPase still showed a 4.1 times lower K(+) sensitivity than that of the rat
enzyme. This means that the difference in K(+) sensitivity of the rat and pig
gastric H(+), K(+)-ATPase is not only due to a different lipid composition but
also to the structure of either the alpha- or beta-subunit. Expression of hybrid
enzymes in Sf9 cells showed that the difference in K(+) sensitivity between the
rat and pig gastric H(+),K(+)-ATPase is primarily due to differences in the beta
subunit.
PMID- 11004563
TI - Modifications of aclacinomycin T by aclacinomycin methyl esterase (RdmC) and
aclacinomycin-10-hydroxylase (RdmB) from Streptomyces purpurascens.
AB - The genes rdmB and rdmC of Streptomyces purpurascens encoding aclacinomycin
modifying enzymes RdmB and RdmC were expressed in Streptomyces lividans TK24. In
contrast to the earlier suggestion that RdmC may be an esterase that causes the
removal of the carbomethoxy group from the 10 position of aclacinomycins, RdmC
functions as an aclacinomycin methyl esterase and catalyzes the removal of the
methoxy group from the C-15 position of aclacinomycin T producing 15
demethoxyaclacinomycin T. RdmB acts upon C-10 of 15-demethoxyaclacinomycin T and
is able to remove the carboxylic group from the C-10 position. It functions also
as an aclacinomycin-10-hydroxylase being able to add a hydroxyl group at the
same, C-10 position in vitro. Aclacinomycin methyl esterase was purified to
apparent homogeneity from S. lividans carrying the rdmC and aclacinomycin-10
hydroxylase as a glutathione S-transferase fusion construct from Escherichia coli
carrying the rdmB gene, respectively. Aclacinomycin methyl esterase functions as
a monomer and aclacinomycin-10-hydroxylase as a tetramer. Aclacinomycin methyl
esterase has an exceptionally high temperature stability and has an apparent K(m)
for aclacinomycin T of 15.5 microM. The introduction of rdmC and rdmB in a
Streptomyces galilaeus mutant HO38 produced the same modifications of
aclacinomycin T in vivo as aclacinomycin methyl esterase and aclacinomycin-10
hydroxylase in vitro.
PMID- 11004564
TI - Trichloroacetic acid and trifluoroacetic acid-induced unfolding of cytochrome c:
stabilization of a native-like folded intermediate(1).
AB - A systematic investigation of trichloroacetic acid (TCA) and trifluoroacetic acid
(TFA)-induced equilibrium unfolding of native horse cytochrome c has been carried
out using a combination of optical spectroscopy and electrospray ionization mass
spectroscopy (ESI MS). In the presence of an increasing concentration of TCA the
native cytochrome c does not undergo significant unfolding but stabilization of a
partially folded intermediate is observed. This TCA-induced partially folding
intermediate of cytochrome c had an enhanced secondary structure and slightly
disrupted tertiary structure compared to native protein and undergoes extensive
unfolding in the presence of TFA. However, in the presence of an increasing
concentration of TFA, cytochrome c was found to undergo extensive unfolding
characterized by a significant breakdown of the secondary and tertiary structure
of protein. The TFA-unfolded cytochrome c was found to undergo folding in the
presence of TCA and low guanidine hydrochloride (GdmCl) resulting in the
stabilization of the partially folded intermediate. The effectiveness of TCA as
compared to TFA in the stabilization of intermediates was further supported by
the observation that low concentrations of TCA were found to induce refolding of
HCl-denatured cytochrome c whereas, under similar concentrations of acid, no
significant effect on the unfolded structure of protein was observed in the
presence of TFA. ESI MS studies indicated that the trichloroacetate anion has a
greater affinity for cytochrome c compared to trifluoroacetate anion, which might
be the reason for the stabilization of the native-like folded intermediate during
TCA-induced denaturation of cytochrome c as compared to extensive unfolding
observed in the presence of TFA.
PMID- 11004565
TI - Colloidal properties of human transferrin receptor in detergent free solution.
AB - The colloidal properties of transferrin receptor, isolated from human placenta,
in detergent free solution has been investigated by light scattering techniques
and analytical ultracentrifugation. In detergent free solution at 293.2 K, hTfR
forms stable aggregates with an apparent hydrodynamic radius of 17 nm. The
molecular mass was determined by ultracentrifugation to lie between (1722+/-87)
kDa (sedimentation equilibrium) and (1675+/-46) kDa (sedimentation velocity).
This implies that the aggregates are build up from nine hTfR dimers. Based on
model calculations, which are in good agreement with the experimental data, we
propose a torus-like structure for the aggregates. Upon pH shift from pH 7.5 to
5.0 or removal of the N-linked carbohydrate chains, formation of larger
aggregates is induced. These aggregates can be described in terms of porous
fractal structures. We propose a simple model, which accounts for that behaviour
assuming that the aggregation is mainly due to the reduction of negative surface
charge.
PMID- 11004566
TI - Active site studies of bovine alpha1-->3-galactosyltransferase and its secondary
structure prediction.
AB - The catalytic domain of bovine alpha1-->3-galactosyltransferase (alpha3GalT),
residues 80-368, have been cloned and expressed, in Escherichia coli. Using a
sequential purification protocol involving a Ni(2+) affinity column followed by a
UDP-hexanolamine affinity column, we have obtained a pure and active protein from
the soluble fraction which catalyzes the transfer of galactose (Gal) from UDP-Gal
to N-acetyllactosamine (LacNAc) with a specific activity of 0.69 pmol/min/ng. The
secondary structural content of alpha3GalT protein was analyzed by Fourier
transform infrared (FTIR) spectroscopy, which shows that the enzyme has about 35%
beta-sheet and 22% alpha-helix. This predicted secondary structure content by
FTIR spectroscopy was used in the protein sequence analysis algorithm, developed
by the Biomolecular Engineering Research Center at Boston University and Tasc
Inc., for the assignment of secondary structural elements to the amino acid
sequence of alpha3GalT. The enzyme appears to have three major and three minor
helices and five sheet-like structures. The studies on the acceptor substrate
specificity of the enzyme, alpha3GalT, show that in addition to LacNAc, which is
the natural substrate, the enzyme accepts various other disaccharides as
substrates such as lactose and Gal derivatives, beta-O-methylgalactose and beta-D
thiogalactopyranoside, albeit with lower specific activities. There is an
absolute requirement for Gal to be at the non-reducing end of the acceptor
molecule which has to be beta1-->4-linked to a second residue that can be more
diverse in structure. The kinetic parameters for four acceptor molecules were
determined. Lactose binds and functions in a similar way as LacNAc. However, beta
O-methylgalactose and Gal do not bind as tightly as LacNAc or lactose, as their
K(ia) and K(A) values indicate, suggesting that the second monosaccharide is
critical for holding the acceptor molecule in place. The 2' and 4' hydroxyl
groups of the receiving Gal moiety are important in binding. Even though there is
large structural variability associated with the second residue of the acceptor
molecule, there are constraints which do not allow certain Gal-R sugars to be
good acceptors for the enzyme. The beta1-->4-linked residue at the second
position of the acceptor molecule is preferred, but the interactions between the
enzyme and the second residue are likely to be non-specific.
PMID- 11004567
TI - Phosphohexose isomerase/autocrine motility factor/neuroleukin/maturation factor
is a multifunctional phosphoprotein.
AB - Phosphohexose isomerase (PHI) is a member of the ectoenzyme/exoenzyme family and
plays a key role in both glycolysis and gluconeogenesis pathways. Upon secretion
PHI acts as a cytokine with tumor autocrine motility factor (AMF), neuroleukin
(NLK) and maturation factor (MF) functions. Signaling is initiated by its binding
to a cell surface 78 kDa glycoprotein (gp78). However, since PHI protein is a
'leaderless' secretory protein, released from cells via a non-classical route(s),
we questioned whether the molecule undergoes post-translation modification while
retaining proper folding and maintaining intact enzymatic and motogenic
activities. To address this, we have generated, expressed and isolated a
recombinant human AMF (rhAMF). The rhAMF retained the biological activities of
the native AMF, i.e., catalyzes phosphohexose isomerization and stimulated cell
motility. Additionally, we show here that human PHI is phosphorylated at serine
185 by casein kinase II (CK II) and we provide experimental evidence suggesting
that this phosphorylation is associated with secretion, thus providing insights
for elucidating the intracellular signal transmission of cell response to
stimulation by AMF/NLK/MF.
PMID- 11004568
TI - Diverse mechanisms of inhibition of pyruvate dehydrogenase kinase by structurally
distinct inhibitors.
AB - The mechanism of action of structurally distinct pyruvate dehydrogenase kinase
(PDK) inhibitors was examined in assays with experimental contexts ranging from
an intact pyruvate dehydrogenase complex (PDC) with and without supplemental ATP
or ADP to a synthetic peptide substrate to PDK autophosphorylation. Some
compounds directly inhibited the catalytic activity of PDKs. Some of the
inhibitor classes tested inhibited autophosphorylation of recombinant PDK1 and
PDK2. During these studies, PDC was shown to be directly inhibited by a novel
mechanism; the addition of supplemental recombinant PDKs, an effect that is ADP
dependent and partly alleviated by members of each of the compound classes
tested. Overall, these data demonstrate that small molecules acting at diverse
sites can inhibit PDK activity.
PMID- 11004569
TI - Structure-function studies on Taiwan cobra long neurotoxin homolog.
AB - A novel long neurotoxin homolog was purified from Naja naja atra (Taiwan cobra)
venom using the combination of ion exchange chromatography and reverse phase high
performance liquid chromatography. The determined protein sequence was
essentially the same as that deduced from the cDNA amplified by reverse
transcriptase-polymerase chain reaction. The long neurotoxin homolog exhibited an
activity that inhibited acetylcholine-induced muscle contractions, as with N.
naja atra cobrotoxin. The degree of inhibition caused by the addition of long
neurotoxin homolog was approximately 70% of that observed with the addition of
cobrotoxin. Unlike the well-known short and long neurotoxins, this neurotoxin
homolog contained two additional cysteine residues forming a disulfide linkage in
the N-terminal region. Circular dichroism measurement and computer models of the
neurotoxin reveal that its secondary structure was not abundant in beta-sheet as
noted with short and long neurotoxins. This less ordered structure may be
associated with the lower activity noted with the long neurotoxin homolog.
Together with the finding that the known long neurotoxin homologs exclusively
appear in the venoms of the Naja and Bungarus genera, the long neurotoxin
homologs should represent an evolutionary branch from the long and short
neurotoxins in the Elapidae family.
PMID- 11004570
TI - Mechanism of the inhibition of milk xanthine oxidase activity by metal ions: a
transient kinetic study.
AB - The nature and mechanism of the inhibition of the oxidoreductase activity of milk
xanthine oxidase (XO) by Cu(2+), Hg(2+) and Ag(+) ions has been studied by steady
state and stopped flow transient kinetic measurements. The results show that the
nature of the inhibition is noncompetitive. The inhibition constants for Cu(2+)
and Hg(2+) are in the micromolar and that for Ag(+) is in the nanomolar range.
This suggests that the metal ions have strong affinity towards XO. pH dependence
studies of the inhibition indicate that at least two ionisable groups of XO are
involved in the binding of these metal ions. The effect of the interaction of the
metal ions on the reductive and oxidative half reactions of XO has been
investigated, and it is observed that the kinetic parameters of the reductive
half reaction are not affected by these metal ions. However, the interaction of
these metal ions with XO significantly affects the kinetic parameters of the
oxidative half reaction. It is suggested that this may be the main cause for the
inhibition of XO activity by the metal ions.
PMID- 11004571
TI - Characterisation of a homogeneous plant aminoaldehyde dehydrogenase.
AB - According to our knowledge, this is the first purification method developed,
enabling isolation of a homogeneous aminoaldehyde dehydrogenase (AMADH) from
etiolated pea seedlings. The procedure involved initial purification with
precipitants followed by three low pressure chromatographic steps. Partially
purified enzyme was further subjected to fast protein liquid chromatography on a
Mono Q column and to affinity-interaction chromatography on 5'-AMP Sepharose.
Purity of the final enzyme preparation was checked by sodium dodecyl sulfate
polyacrylamide gel electrophoresis and chromatofocusing. Pea AMADH exists as a
tetramer of 230 kDa in the native state, a molecular mass of one subunit was
determined as 57 kDa. The enzyme was found to be an acidic protein with pI 5.4.
AMADH showed a broad substrate specificity utilising various aminoaldehydes (C3
C6) as substrates. The best substrate of pea AMADH was 3-aminopropionaldehyde,
the enzyme also efficiently oxidised 4-aminobutyraldehyde and omega
guanidinoanalogues of the aminoaldehydes. Pea AMADH was inhibited by SH reagents,
several elementary aldehydes and metal-binding agents. Although AMADH did not
oxidise betaine aldehyde at all, the N-terminal amino acid sequence of the enzyme
shows a high degree of homology with those of plant betaine aldehyde
dehydrogenases (BADHs) of spinach, sugar beet and amaranth. Several conserved
amino acids were found in comparison with BADH from cod liver of known crystal
structure.
PMID- 11004572
TI - The role of tryptophan residues in substrate binding to catalytic domains A and B
of xylanase C from Fibrobacter succinogenes S85.
AB - Oxidation of the isolated catalytic domain B of xylanase C (XynC-B) from
Fibrobacter succinogenes with N-bromosuccinimide (NBS) resulted in the
modification of five of the seven Trp residues present in the enzyme. Hydrolytic
activity of the enzyme was rapidly lost upon initiation of oxidation as a molar
ratio of about two NBS molecules per molar equivalent of protein was sufficient
to cause 50% inhibition of enzyme activity, and the addition of five molar
equivalents of NBS resulted in less than 10% activity. Pre-incubation of XynC-B
with the competitive inhibitor D-xylose resulted in the apparent protection of
two Trp residues from oxidation. Xylose protection of the enzyme also resulted in
a maintenance of activity, with 60% activity still evident after addition of 8-9
molar equivalents of NBS. This protection from inactivation was enhanced by the
inclusion of xylohexaose in reaction mixtures. Under these conditions, however, a
further Trp residue was protected from NBS oxidation. The three protected Trp
residues were identified as Trp135, Trp161 and Trp202 by differential labelling
and peptide mapping of NBS-oxidized preparations of the xylanase employing a
combination of electrospray mass spectroscopic analysis and N-terminal
sequencing. By analogy to the known structures of the family 11 xylanases, the
fully conserved Trp202 residue is located on the only alpha-helix present in the
enzymes, at the interface between it and the back of the beta-sheet which forms
the active site cleft. Trp135 represents a highly conserved aromatic residue in
family 11, but it is replaced with Thr in domain A of F. succinogenes xylanase C.
To investigate the role of Trp135 in conferring the different activity profile of
domain B relative to domain A, the Trp135Thr and Trp135Ala derivatives of domain
B were prepared by site-directed mutagenesis. However, the kinetic parameters of
the two domain B derivatives were not significantly different compared to the
wild-type enzyme as reflected by K(M) and k(cat) values and product distribution
profiles. Similar results were obtained with the Trp161Ala derivative of domain
B, indicating that these two residues do not directly participate in the binding
of substrate but likely form the foundation for binding subsite 2.
PMID- 11004573
TI - High-pressure denaturation of apomyoglobin.
AB - The pressure denaturation of wild type and mutant apomyoglobin (apoMb) was
investigated using a high-pressure, high-resolution nuclear magnetic resonance
and high-pressure fluorescence techniques. Wild type apoMb is resistant to
pressures up to 80 MPa, and denatures to a high-pressure intermediate, I(p),
between 80 and 200 MPa. A further increase of pressure to 500 MPa results in
denaturation of the intermediate. The two tryptophans, both in the A helix,
remain sequestered from solvent in the high-pressure intermediate, which retains
some native NOESY cross peaks in the AGH core as well as between F33 and F43.
High-pressure fluorescence shows that the tryptophans remain inaccessible to
solvent in the I(p) state. Thus the high-pressure intermediate has some
structural properties in common with the apoMb I(2) acid intermediate. The
resistance of the AGH core to pressures up to 200 MPa provides further evidence
that the intrinsic stability of these alpha-helices is responsible for their
presence in a number of equilibrium intermediates as well as in the earliest
kinetic folding intermediate. Mutations in the AGH core designed to disrupt
packing by burying a charge or increasing the size of a hydrophobic residue
significantly perturbed the unfolding of native apoMb to the high-pressure
intermediate. The F123W and S108L mutants both unfolded at lower pressures, while
retaining some resistance to pressures below 50 MPa. The charge burial mutants,
A130K and S108K, are not stable at very low pressures and both denature to the
intermediate by 100 MPa, half of the pressure required for wild type apoMb. Thus
a similar intermediate state is created independent of the method of
perturbation, and mutations have similar effects on native state destabilization
for both methods of denaturation. These data suggest that equilibrium
intermediates that can be formed through different means are likely to resemble a
kinetic intermediate.
PMID- 11004574
TI - Crystallization and preliminary X-ray crystallographic analysis of NADPH:
azodicarbonyl/quinone oxidoreductase, a plant zeta-crystallin.
AB - Arabidopsis thaliana P1 protein was crystallized using the hanging drop vapor
diffusion method in 0.1 M piperazine-1, 4-bis(2-ethanesulfonic acid) buffer,
containing 14% polyethylene glycol 6000 and 0.2 M magnesium acetate at pH 6.5 and
20 degrees C. The crystals are orthorhombic and belong to the space group
P2(1)2(1)2(1) with unit cell dimensions of a=49.8, b=122.4 and c=149. 9 A. The
diffraction data up to 2.9 A were collected by a multiwire area detector.
PMID- 11004575
TI - Purification, crystallisation and preliminary X-ray study of haemoglobin from
Crocodilis palustris and Crocodilis porosus.
AB - The unsolved three-dimensional structure of crocodile haemoglobin and its
prospects as a blood substitute have led us to initiate the purification and
crystallisation of haemoglobin molecules from crocodile species (Crocodilis
palustris or mugger and Crocodilis porosus or salt water crocodile). The work has
resulted in the prevention of polymerisation of naked haemoglobin molecules using
N-ethylmaleimide or iodoacetamide. The purified monomeric haemoglobin molecule of
C. porosus was crystallised in two different forms and X-ray diffraction data
were collected up to 2 A resolution for both forms. Form I: a=53.62, b=53.55,
c=103.77 A; beta=93.35 degrees, space group P2(1), Z=2. Form II: a=71.30,
b=54.70, c=80.00 A; beta=106.4 degrees, space group P2(1), Z=2. Structure
solution and rigid body refinement of form I data resulted in a model with
R(free)=0.42 and R=0.35.
PMID- 11004576
TI - Escherichia coli is able to produce heterologous tetraheme cytochrome c(3) when
the ccm genes are co-expressed.
AB - The production of Desulfovibrio vulgaris Hildenborough cytochrome c(3) (M(r)
13000), which is a tetraheme cytochrome, in Escherichia coli was examined. This
cytochrome was successfully produced in an E. coli strain co-expressing the
ccmABCDEFGH genes involved in the cytochrome c maturation process. The
apocytochrome c(3) was matured in either anaerobic or aerobic conditions, but
aerobic growth in the presence of delta-aminolevulinic acid was found to be best
for cytochrome c(3) production. Site-directed mutagenesis was performed to
investigate the effect of the presence of four amino acids in between the two
cysteines of the heme binding sites 2 and 4 on the maturation of holocytochrome
c(3) in E. coli.
PMID- 11004577
TI - Contributions of protein disulfide isomerase domains to its chaperone activity.
AB - Protein disulfide isomerase (PDI), a member of the thioredoxin (Trx) superfamily,
consists of five consecutive domains, a-b-b'-a'-c. Domain combinations, AB, A'C,
B'A'C and AB-C, and hybrids of PDI domains with Trx, Trx-C and Trx-B'A'C, have
been constructed and expressed in Escherichia coli to examine the contributions
of PDI domains to its enzyme and chaperone activities. All the combination and
hybrid products are considerably less active than intact PDI in their enzyme
activities. Recombinant products containing C, at low concentrations, inhibit the
reactivation of lysozyme in HEPES buffer, while those without C do not. Only the
intact PDI molecule and the hybrid molecule, Trx-B'A'C, but to a much lower
level, show general chaperone activity in assisting the reactivation of denatured
D-glyceraldehyde-3-phosphate dehydrogenase. It is suggested that all domains of
PDI contribute to the binding of target protein for its chaperone activity.
PMID- 11004578
TI - Enthalpic destabilization of glycosylated lysozymes constructed by genetic
modification.
AB - To understand the role of polyglycosylation in protein stability, the
thermodynamic changes in the denaturation of various polymannosyl lysozyme
mutants (R21T, G49N, R21T/G49N) constructed by genetic modification were analyzed
using differential scanning calorimetry (DSC). The denaturation temperature and
the enthalpy change for unfolding of the lysozymes were reduced with an increase
in the length of the polymannose chain and the number of binding sites to a
protein, although the polymannosyl lysozymes revealed apparent heat stability in
that no aggregation was observed and the enzymatic activity was conserved under
conditions in which the wild-type lysozyme coagulated [S. Nakamura et al., J.
Biol. Chem. 268 (1993) 12706-12712]. The reversibility of the denaturation of
polymannosyl lysozymes was observed in the DSC curves obtained by reheating after
heat denaturation, while it was not observed for the wild-type lysozyme. Based on
these results, the polymannosyl lysozyme seems to easily refold due to the
excellent reversibility of denaturation, despite the decreases in the enthalpic
stabilization due to the strain in the protein molecule by the introduction of a
polysaccharide chain.
PMID- 11004579
TI - The native metastable fold of C1-inhibitor is stabilized by disulfide bonds.
AB - C1-inhibitor is a member of the serpin family of proteinase inhibitors and is an
important inhibitor of complement and contact system proteinases. The native
protein has the characteristic serpin feature of being in a kinetically trapped
metastable state rather than in the most stable state it could adopt. A
consequence of this is that it readily forms loop-sheet dimers and polymers, by a
mechanism believed to be the same as observed with other serpins. An unusual
feature of C1-inhibitor is that it has a unique amino-terminal domain, of unknown
function, held to the serpin domain by two disulfide bonds not found in other
serpins. We report here that reduction of these bonds by DTT, causes a
conformational change such that the reactive center loop inserts into beta-sheet
A. This form of C1-inhibitor is less stable to heat and urea than the native
protein, and is more susceptible to extensive degradation by trypsin. These data
show that the disulfide bonds in C1-inhibitor are required for the protein to be
stabilized in the metastable state with the reactive center loop expelled from
beta-sheet A.
PMID- 11004580
TI - Specific interaction of lipoate at the active site of rhodanese.
AB - Dihydrolipoate is an acceptor of the rhodanese-bound sulfane sulfur atom, as
shown by analysis of the elementary steps of the reaction catalyzed by rhodanese.
The crystal structure of sulfur-substituted rhodanese complexed with the non
reactive oxidized form of lipoate has revealed that the compound is bound at the
enzyme active site, with the dithiolane ring buried in the interior of the cavity
and the carboxylic end pointing towards the solvent. One of the sulfur atoms of
the ligand in the unproductive complex is relatively close to the sulfane sulfur
bound to Cys-247, the sulfur that is transferred during the catalytic reaction.
This mode of binding of lipoate is likely to mimic that of dihydrolipoate. The
results presented here support the possible role of dihydrolipoate as sulfur
acceptor substrate of rhodanese in an enzymatic reaction that might serve to
provide iron-sulfur proteins with inorganic sulfide.
PMID- 11004581
TI - Comparison of HOCl traps with myeloperoxidase inhibitors in prevention of low
density lipoprotein oxidation.
AB - In this study, the production of the highly toxic oxidant hypochlorous acid
(HOCl) by the phagocytic enzyme myeloperoxidase (MPO) was quantitated and the
concomitant alterations of low density lipoprotein (LDL) were analyzed in view of
the potential role of LDL in atherosclerosis. Using the monochlorodimedone assay,
it was found that HOCl is produced in micromolar concentrations. The kinetics of
the decrease of tryptophan fluorescence appeared to be a sensitive method to
monitor LDL alterations under near in vivo conditions. Therefore, this method was
used to subsequently compare the effectiveness of MPO inhibitors that block
production of HOCl with compounds that act as HOCl traps. The efficiency of MPO
inhibitors to prevent LDL damage increased in the series benzohydroxamic acid <
salicylhydroxamic acid < 3-amino-1,2,4-triazole < sodium azide < potassium
cyanide < p-hydroxy-benzoic acid hydrazide, while for the HOCl traps the
protective efficiency increased in the series glycine < taurine < methionine. We
conclude that HOCl traps may have high potential therapeutic impact in vivo due
to their low toxicity, although high concentrations of them would have to reach
sites of inflammation. In contrast, only low concentrations of a specific MPO
inhibitor would be required to irreversibly inhibit the enzyme.
PMID- 11004582
TI - Characterization of a heme c nitrite reductase from a non-ammonifying
microorganism, Desulfovibrio vulgaris Hildenborough.
AB - A cytochrome c nitrite reductase (NiR) was purified for the first time from a
microorganism not capable of growing on nitrate, the sulfate-reducing bacterium
Desulfovibrio vulgaris Hildenborough. It was isolated from the membranes as a
large heterooligomeric complex of 760 kDa, containing two cytochrome c subunits
of 56 and 18 kDa. This complex has nitrite and sulfite reductase activities of
685 micromol NH(4)(+)/min/mg and 1.0 micromol H(2)/min/mg. The enzyme was studied
by UV-visible and electron paramagnetic resonance (EPR) spectroscopies. The
overall redox behavior was determined through a visible redox titration. The data
were analyzed with a set of four redox transitions, with an E(0)' of +160 mV (12%
of total absorption), -5 mV (38% of total absorption), -110 mV (38% of total
absorption) and -210 mV (12% of total absorption) at pH 7.6. The EPR spectra of
oxidized and partially reduced NiR show a complex pattern, indicative of multiple
heme-heme magnetic interactions. It was found that D. vulgaris Hildenborough is
not capable of using nitrite as a terminal electron acceptor. These results
indicate that in this organism the NiR is not involved in the dissimilative
reduction of nitrite, as is the case with the other similar enzymes isolated so
far. The possible role of this enzyme in the detoxification of nitrite and/or in
the reduction of sulfite is discussed.
PMID- 11004583
TI - Incorporation of nitrotyrosine into alpha-tubulin by recombinant mammalian
tubulin-tyrosine ligase.
AB - Tubulin-tyrosine ligase (TTL, EC 6.3.2.25) from porcine brain, which catalyses
the readdition of tyrosine to the C-terminus of detyrosinated alpha-tubulin, was
cloned and expressed in Escherichia coli as a glutathione S-transferase-fusion
protein. Upon cleavage of the immobilised fusion protein, an electrophoretically
homogeneous enzyme was obtained. Recombinant TTL, which exhibited similar
catalytic properties as the mammalian enzyme purified from brain tissue, was
capable of using nitrotyrosine as an alternative substrate in vitro.
Incorporation of tyrosine into tubulin was competitively inhibited by
nitrotyrosine with an apparent K(i) of 0.24 mM. The TTL-catalysed incorporation
of nitrotyrosine as sole substrate into alpha-tubulin was clearly detectable at
concentrations of 10 microM by immunological methods using nitrotyrosine specific
antibodies. However, in competition with tyrosine 20-fold higher concentrations
of nitrotyrosine were necessary before its incorporation became evident. Analysis
of the C-terminal peptides of in vitro modified alpha-tubulin by MALDI-MS
confirmed the covalent incorporation of nitrotyrosine into tubulin by TTL. In
contrast to the C-terminal tyrosine, pancreatic carboxypeptidase A was incapable
of cleaving nitrotyrosine from the modified alpha-tubulin.
PMID- 11004584
TI - Eosin interaction of alpha-synuclein leading to protein self-oligomerization.
AB - Among various dyes including congo red, thioflavin S, thioflavin T, eosin,
rhodamine 6G, and phenol red, the eosin was the only dye that induced self
oligomerization of alpha-synuclein in the presence of a chemical coupling reagent
of N-(ethoxycarbonyl)-2-ethoxy-1, 2-dihydroquinoline. To analyze chemical nature
of the eosin interaction with alpha-synuclein, the phenomenon of self
oligomerization was further examined with eosin congeners such as ethyl eosin,
eosin B, phloxine B, erythrosin B, and rose bengal. The followings are the
conclusions we have reached. First of all, intactness of the benzoate moiety of
eosin and the negative charge on the carboxylic group of the dye are important
factors leading to the specific interaction with alpha-synuclein. Secondly, the
localized negative charge on the xanthene moiety of eosin is another critical
factor for the interaction. As far as substituting halides are concerned,
bromides and iodides on the xanthene moiety of the dyes do not make any
difference on the alpha-synuclein interaction because both eosin and erythrosin B
have induced the common phenomenon of self-oligomerization. The binding curve
between eosin and alpha-synuclein was sigmoidal as the dye concentrations were
increased. A double reciprocal plot of the saturation curve showed that the
maximum number of eosin binding sites on alpha-synuclein was 1.85 with a
dissociation constant of 390 microM. The dye binding to the protein appeared to
occur via a positive cooperativity. The eosin binding site(s) was suggested to be
located predominantly on the NAC region and partly related to the acidic C
terminus of alpha-synuclein. It has been, therefore, expected that this
information might be useful to develop alpha-synuclein interactive molecules,
which could provide eventual preventive or possible therapeutic means against
various alpha-synuclein related disorders including Parkinson's disease.
PMID- 11004585
TI - STIM1: a novel phosphoprotein located at the cell surface.
AB - STIM1 is a novel candidate growth suppressor gene mapping to the human chromosome
region 11p15.5 that is associated with several malignancies. STIM1 overexpression
studies in G401 rhabdoid tumour, rhabdomyosarcoma and rodent myoblast cell lines
causes growth arrest, consistent with a potential role as a tumour growth
suppressor. We used highly specific antibodies to show by immunofluorescence and
cell surface biotinylation studies that STIM1 is located at the cell surface of
K562 cells. Western blot analysis revealed that the 90-kDa STIM1 protein is
ubiquitously expressed in various human primary cells and tumour cell lines.
STIM1 is not secreted from cells and does not appear to undergo proteolytic
processing. We show evidence of post-translational modification of STIM1, namely
phosphorylation and N-linked glycosylation. Phosphorylation of STIM1 in vivo
occurs predominantly on serine residues. Thus, STIM1, the putative tumour growth
suppressor gene is ubiquitously expressed and has features of a regulatory cell
surface phosphoprotein.
PMID- 11004605
TI - Adapting to multiple personalities: Cbl is also a RING finger ubiquitin ligase.
PMID- 11004606
TI - A growing role for Rho family GTPases as intermediaries in growth factor- and
adhesion-dependent cell cycle progression.
PMID- 11004607
TI - Fish oil diet affects on oxidative senescence of red blood cells linked to
degeneration of spleen cells in mice.
AB - The effect of dietary polyunsaturated fatty acids and alpha-tocopherol
supplementation on erythrocyte lipid peroxidation and immunocompetent cells in
mice was studied comparatively using seven dietary oils (15% oil/diet, w/w)
including fish oil rich in eicosapentaenoic acid (EPA, 20:5, n-3) and
docosahexaenoic acid (DHA, 22:6, n-3). A 43% increase in spleen weight, about
twice as many spleen cells and no change in the subpopulations of spleen cells,
as well as a significant depression of mitogen-induced blastogenesis of both T
and B cells in the spleen were observed in mice fed fish oil for 30 days in
comparison with soybean oil diet-fed mice. In the fish oil diet-fed mice,
membranous lipid hydroperoxide (hydroperoxides of phosphatidylcholine and
phosphatidylethanolamine) accumulation as a marker of oxidative senescence in red
blood cells (RBC) was 2.7-3.5 times higher than that in mice fed soybean oil,
although there was no difference in the plasma phosphatidylcholine hydroperoxide
concentration. In spite of the supplementation of alpha-tocopherol to up to 10
times the level in the basal diet, the degeneration of spleen cells and the
stimulated oxidative senescence of RBC found by the fish oil feeding could not be
prevented. The results suggest that oral intake of excess polyunsaturated fatty
acids, i.e. EPA and DHA, in a fish oil diet can lead to acceleration of membrane
lipid peroxidation resulting in RBC senescence linked to the lowering of immune
response of spleen cells, and that supplementation of alpha-tocopherol as
antioxidant does not always effectively prevent such oxidative degeneration as
observed in spleen cells and RBC in vivo.
PMID- 11004608
TI - 1H-NMR lipid profiles of human blood platelets; links with coronary artery
disease.
AB - Blood platelets are closely involved in the early development of atherosclerosis
and in the events that lead to thrombosis, both of which are dominating factors
in coronary artery disease (CAD). The aim of the present study was to evaluate
the platelet lipid profiles of patients suffering from CAD and explore the
possibility of a link between platelet lipids and CAD, using high-resolution high
field proton nuclear magnetic resonance spectroscopy as the analytical tool. The
total platelet lipid profiles of healthy volunteers were compared with those of
patients presenting with chest pain requiring coronary angiography. Two lipid
groups changed significantly: cholesterol increased by 16.5% and total
diacylglycerophospholipids decreased by 15.7%. There was also a significant
decrease of the ethanolamine-containing phospholipids, by 4.7%; the extent of
unsaturation of the fatty acid chains, by 0.2, and increase of the linoleate
content of the fatty acid chains, by 1.9%. Our results suggest that platelet
lipid abnormalities occur in patients with CAD and these changes may predate the
development of overt atherosclerosis.
PMID- 11004609
TI - Arachidonic acid-containing phosphatidylcholine inhibits lymphocyte proliferation
and decreases interleukin-2 and interferon-gamma production from concanavalin A
stimulated rat lymphocytes.
AB - The proliferation of concanavalin A (Con A)-stimulated rat lymphocytes was
markedly inhibited by phosphatidylcholine containing arachidonic and stearic
acids (PC(A-S)), but not by phosphatidylcholine containing oleic and stearic
acids or phosphatidylinositol containing arachidonic and stearic acids. The
concentration of PC(A-S) which inhibited Con A-stimulated proliferation by 50%
was 31 microM and near total inhibition was observed at 154 microM .
Phosphatidylserine containing only oleic acid enhanced proliferation by 37% at a
concentration of 31 microM , but phosphatidylethanolamine and phosphatidylcholine
containing only oleic acid did not affect proliferation at this concentration. It
is concluded that both the head group and the fatty acid composition contribute
to the influence of phospholipids on lymphocyte proliferation. The effects of
PC(A-S) on T-lymphocyte responses were investigated further. In parallel with the
inhibition of proliferation PC(A-S) caused a concentration-dependent decrease in
the production of the Th1-type cytokines interleukin (IL)-2 and interferon (IFN)
gamma; inhibition of cytokine production was >85% at the highest concentration of
PC(A-S) used (154 microM ). Production of the Th2-type cytokines IL-4 and IL-10
was not affected. The possible role of prostaglandins in mediating the effects of
PC(A-S) was examined by adding indomethacin into the medium and the participation
of lipid peroxidation was examined by adding vitamin E and vitamin C.
Indomethacin and vitamin E did not affect the inhibition caused by PC(A-S) but
vitamin C caused a partial reversal. It is concluded that inhibition of T
lymphocyte proliferation by phospholipids involves both the head group and the
fatty acyl chains, that this inhibition is not mediated by prostaglandins but may
involve some form of oxidant stress and that some phospholipids (e.g., PC(A-S))
can markedly influence cytokine profiles.
PMID- 11004610
TI - Assay of microsomal oxysterol 7alpha-hydroxylase activity in the hamster liver by
a sensitive method: in vitro modulation by oxysterols.
AB - A method of assaying hepatic cytochrome P-450, oxysterol 7alpha-hydroxylase
(CYP7B), was developed by combining the use of 25-[26,27-(3)H]hydroxycholesterol
as a substrate and hydroxypropyl-beta-cyclodextrin as a substrate vehicle. When
these assay conditions were tested, an undesirable transformation was observed of
the reaction product, 7alpha,25-dihydroxycholesterol, into 3-oxo-7alpha,25
dihydroxy-4-cholesten by the activity of 3beta-hydroxy-Delta(5)-C(27) steroid
oxydoreductase, a microsomal NAD(+) and NADP(+) dependent enzyme of bile acid
metabolism. A great improvement was reached by using a continuous NADPH
generating system which constantly re-transforms NADP(+) into NADPH, thus
inhibiting this activity. This improved CYP7B assay, comparable to our previously
described assay for cholesterol 7alpha-hydroxylase (CYP7A), allowed a 3-fold
increase of the apparent enzyme activity. The possibility to simultaneously
measure CYP7A and CYP7B activities on the same microsomal preparation was
investigated. A marked decrease (-33%) in the CYP7B activity was noticed, while
that of CYP7A remained unchanged. The CYP7B activity was observed to be inhibited
by cholesterol (-30%) and also by the oxysterols 7alpha-hydroxycholesterol (
21%), 7beta-hydroxycholesterol (-25%) and epicoprostanol (-20%), and by
cyclosporin A (-26%). It can be concluded that this sensible and easy to perform
CYP7B assay allows to observe, at least in vitro, a modulation of the enzyme
activity by oxysterols.
PMID- 11004611
TI - Cloning and promoter analysis of the cotton lipid transfer protein gene Ltp3(1).
AB - A cotton Ltp3 gene and its 5' and 3' flanking regions have been cloned with a PCR
based genomic DNA walking method. The amplified 2.6 kb DNA fragment contains
sequences corresponding to GH3 cDNA which has been shown to encode a lipid
transfer protein (LTP3). The gene has an intron of 80 bp which is located in the
region corresponding to the C-terminus of LTP3. The Ltp3 promoter was
systematically analyzed in transgenic tobacco plants by employing the Escherichia
coli beta-glucuronidase gene (GUS) as a reporter. The results of histochemical
and fluorogenic GUS assays indicate that the 5' flanking region of the Ltp3 gene
contains cis-elements conferring the trichome specific activity of Ltp3 promoter.
PMID- 11004612
TI - Cicatricial pemphigoid.
AB - Cicatricial pemphigoid (CP) is a heterogeneous group of rare, chronic,
subepithelial blistering disorders of the mucous membranes and, occasionally, the
skin, which can have serious and rarely fatal consequences. The most common
clinical features are desquamative gingivitis, oral erosions, and conjunctival
fibrosis. Skin lesions occur less frequently and may present as widespread
vesicles and bullae, as in bullous pemphigoid (BP). In some patients, the
scarring can be a source of significant morbidity because it can result in
odynophagia, strictures of the upper aerodigestive tract, or corneal opacities
leading to eventual blindness. This article is a comprehensive review and
discusses clinical, pathologic, and pathophysiologic aspects of this group of
disorders collectively known as CP. (J Am Acad Dermatol 2000;43:571-91.) LEARNING
OBJECTIVE: At the conclusion of this learning activity, participants should be
familiar with the clinical spectrum of CP, the histopathologic and
immunopathologic characteristics, the differential diagnosis, the treatment, and
the natural history of the disease. Furthermore, this learning activity should
facilitate early diagnosis of CP and should promote the idea that the involvement
of other specialists, including ophthalmologists, otolaryngologists,
gastroenterologists, and oral medicine specialists, as appropriate, will aid in
providing these patients with the highest quality of care.
PMID- 11004613
TI - Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris:
results of a pilot, multicenter, multiple-dose, placebo-controlled study.
AB - BACKGROUND: OKTcdr4a (IMUCLONE) is a humanized anti-CD4 IgG4 monoclonal antibody
that retains the binding and in vitro immunosuppressive properties of the parent
murine antibody. Psoriasis is a chronic disease for which treatment with multiple
doses of monoclonal antibodies is likely to be required for adequate control.
OBJECTIVE: This study was performed to test the efficacy and safety of OKTcdr4a,
given in sequential courses over a period of several weeks, in the treatment of
moderate to severe psoriasis vulgaris. METHODS: Twenty-eight patients (45.6 +/-
10.1 years of age) were studied, with a mean pretreatment Psoriasis Area and
Severity Index (PASI) score of 18.3. In the first double-blind phase of the
study, patients were randomized to receive OKTcdr4a as a 225 mg/course (low
dose), 750 mg/course (high dose), or placebo divided into 3 identical infusions
over a 5-day period. After 42 days, patients who met the criteria for re
treatment with OKTcdr4a were re-treated with the 750 mg/course in an open phase
of the study. RESULTS: After the double-blind course of treatment, the mean PASI
decreased by 11% in the placebo group, by 4% in the low-dose group, and by 17% in
the high-dose group at 15 days. Twenty patients met the criteria for re-treatment
(ie, did not experience a decrease in PASI score of 50% at 42 days). They were re
treated with OKTcdr4a at 43 days with the 750 mg/course in the open phase of the
study. By day 99, the mean PASI score decreased from 19.9 at baseline to 17 in
those patients who had received either placebo or low-dose OKTcdr4a followed by
high-dose OKTcdr4a. In contrast, the mean PASI score decreased from 17.4 at
baseline to only 7.7 in those patients who had received high-dose OKTcdr4a for
both courses. Sustained CD4 saturation was not necessary for sustained clinical
response. No patients had significant changes in circulating CD4(+) T-cell
counts. The infusions were well tolerated. CONCLUSION: Targeting CD4 using
sequential treatments with a humanized monoclonal antibody (OKTcdr4a) may offer
another therapeutic option for the treatment of moderate to severe psoriasis.
PMID- 11004614
TI - Late metastases of cutaneous melanoma: an analysis of 31 patients.
AB - Analysis of data of 6298 patients with cutaneous melanoma seen at the Department
of Dermatology and Allergology at the Ludwig-Maximilians University of Munich
between 1977 and 1998 identified 31 patients who first experienced metastatic
disease 10 or more years after surgical treatment of the primary melanoma. The
mean tumor thickness in patients with late progression of disease was 1.4 mm.
There was no sex predominance. Of 31 patients, 15 (48. 3%) were female and
included both premenopausal and postmenopausal women at the time of initial
diagnosis without any predominance. Sixteen of the 31 patients (51.6%) with late
onset of progression had primary tumors located on the trunk. The prognosis after
relapse was related to the site of recurrence; survival after local or regional
node recurrence was often prolonged, whereas survival after distant metastases
usually was limited. Survival after late recurrence did not correlate with
disease-free survival. A high-risk group for late recurrence could not be
identified. The data emphasize the value of continued clinical follow-up and self
examination for early detection of regional recurrences. We advocate a lifelong
follow-up, also to identify other melanocytic lesions at risk (eg, dysplastic
nevi, secondary or multiple melanomas).
PMID- 11004616
TI - Sensitivity and specificity of clinical, histologic, and immunologic features in
the diagnosis of paraneoplastic pemphigus.
AB - BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease
characterized by the production of autoantibodies mainly directed against
proteins of the plakin family. An overlapping distribution of autoantibody
specificities has been recently reported between PNP, pemphigus vulgaris (PV),
and pemphigus foliaceus (PF), which suggests a relationship between the different
types of pemphigus. OBJECTIVE: Our purpose was to evaluate the sensitivity and
the specificity of clinical, histologic, and immunologic features in the
diagnosis of PNP. METHODS: The clinical, histologic, and immunologic features of
22 PNP patients were retrospectively reviewed and compared with those of 81 PV
and PF patients without neoplasia and of 8 PV and 4 PF patients with various
neoplasms. RESULTS: One clinical and 2 biologic features had both high
sensitivity (82%-86%) and high specificity (83%-100%) whatever the control group
considered: (1) association with a lymphoproliferative disorder, (2) indirect
immunofluorescence (IIF) labeling of rat bladder, and (3) recognition of the
envoplakin and/or periplakin bands in immunoblotting. Two clinicopathologic and
two biologic features had high specificity (87%-100%) but poor sensitivity (27%
59%): (1) clinical presentation associating erosive oral lesions with erythema
multiforme-like, bullous pemphigoid-like, or lichen planus-like cutaneous
lesions; (2) histologic picture of suprabasal acantholysis with keratinocyte
necrosis, interface changes, or lichenoid infiltrate; (3) presence of both anti
epithelial cell surface and anti-basement membrane zone antibodies by IIF; and
(4) recognition of the desmoplakin I and/or BPAG1 bands in immunoblotting.
Interestingly, 45% of patients with PNP presented initially with isolated oral
erosions that were undistinguishable from those seen in PV patients, and 27% had
histologic findings of only suprabasal acantholysis, which was in accordance with
the frequent detection of anti-desmoglein 3 antibodies in PNP sera. CONCLUSION:
The association with a lymphoproliferative disorder, the IIF labeling of rat
bladder, and the immunoblotting recognition of envoplakin and/or periplakin are
both sensitive and specific features in the diagnosis of PNP.
PMID- 11004615
TI - Effect of daily versus intermittent sunscreen application on solar simulated UV
radiation-induced skin response in humans.
AB - BACKGROUND: Acute and chronic skin damage occurs as a consequence of solar UV
radiation exposure. To diminish such skin damage, the dermatologic community
advocates the daily use of sunscreens as part of a sun avoidance strategy.
OBJECTIVE: We determined the effectiveness of a sunscreen product with a
sunscreen protection factor (SPF) of 15 applied daily in preventing UV-induced
histologic damage in human skin compared with the protection afforded by
sunscreens with equal or higher SPF applied intermittently. METHODS: Twenty-four
subjects were exposed to 2 minimal erythema doses of solar-simulated UV on 4
consecutive days. Three sunscreen products were applied to the buttock of each
subject. One SPF 15 product was applied daily before exposure to UV and, to
simulate intermittent product use, an SPF 15 or SPF 29 product was applied on 3
of 4 days, with one missed application on days 2, 3, or 4. Skin biopsy specimens
were taken and processed for routine and immunohistochemical staining. Changes in
number of sunburn cells and Langerhans cells as well as degree of inflammatory
infiltrate and lysozyme immunostaining were determined. RESULTS: There was a
statistically significant increase in the number of sunburn cells, degree of
inflammation, and intensity of lysozyme staining, and there was a decrease in the
number of Langerhans cells at sites where sunscreen application was missed as
compared with unirradiated control and daily SPF 15 sunscreen-treated sites.
CONCLUSION: Our data suggest that daily use of a sunscreen reduces the skin
damage produced by UV exposure compared with intermittent use of equal or higher
SPF products. The daily application of sunscreens in appropriate quantities
reduces the harmful effects of solar UV radiation on skin. Compliance is
essential for maximal benefit of sunscreens.
PMID- 11004617
TI - Prognostic indicators in venous ulcers.
AB - BACKGROUND: Venous ulcers can be difficult to heal, and prognostic factors for
healing have not been fully elucidated. OBJECTIVE: The objective of this study
was to analyze the results of a large multicenter venous ulcer trial to
retrospectively establish prognostic factors for venous ulcer healing. METHODS:
This study examined data from a previously published prospective randomized
placebo-controlled trial of an oral medication versus placebo treatment for
venous ulcers. Local leg ulcer care involved the use of a moisture-retentive
dressing and sustained graduated compression with a paste bandage and a self
adherent wrap. The oral medication or placebo was administered on a daily basis
with the same dressings and bandage system in both groups for 12 weeks. A total
of 165 patients completed the full 12-week treatment period; 83 received
ifetroban, 82 received placebo. RESULTS: There was no statistically significant
difference in outcome between the two groups. The study showed that consistent
local ulcer treatment with a clearly defined system of care was associated with
an unexpectedly high percentage (55%) of long-standing large venous ulcers (mean
duration, 27 months; mean area, 15.9 cm(2)) being healed in both groups. Baseline
ulcer area and duration of leg ulcer were found to be important in predicting
outcome. Ulcers of short duration were found to be most likely to heal. Percent
healing and ulcer area at week 3 were good predictors of 100% healing. Ulcers
that had at least 40% healing by week 3 predicted more than 70% of the outcomes
correctly. CONCLUSION: From this large study it was determined that baseline
ulcer area and ulcer duration are significant predictors of 100% healing and time
to heal. Percent healing and ulcer area at week 3 are good predictors of complete
ulcer healing. Ulcers that are large, long-standing, and slow to heal after 3
weeks of optimal therapy are unlikely to heal rapidly, and might benefit from
alternative therapies.
PMID- 11004618
TI - Raynaud's phenomenon, anticentromere antibodies, and digital necrosis without
sclerodactyly: an entity independent of scleroderma?
AB - We describe 4 women of 43, 73, 84, and 86 years with Raynaud's phenomenon, severe
digital necrosis, and high serum levels of anticentromere antibodies without skin
thickening or internal organ sclerosis. Investigations revealed no diabetes or
arterial vascular disease leading to arterial obstruction. Histologic examination
did not show any dermal sclerosis or calcinosis. The intravenous infusions of
prostaglandin reversed the ischemic lesions in 3 patients. These cases suggest
that the triad Raynaud's phenomenon, anticentromere antibodies and necrosis of
digits without sclerodactyly and sclerosis of internal organ should be considered
as an entity distinct from scleroderma with sclerosis. For this entity we propose
the name RACAND syndrome.
PMID- 11004619
TI - Rapidly progressing mycosis fungoides presenting as follicular mucinosis.
AB - Follicular mucinosis can occur as a primary idiopathic disorder or can arise in
association with benign or malignant disease, most notably mycosis fungoides. We
describe a patient with an aggressive folliculotropic variant of mycosis
fungoides that initially presented as follicular mucinosis with alopecia. One
month after the diagnosis of follicular mucinosis, a diagnosis of mycosis
fungoides was made, and 3 months later inguinal lymph node involvement with
mycosis fungoides developed. A skin biopsy specimen demonstrated prominent
follicular mucinosis with folliculotropism of atypical cells and intrafollicular
Pautrier's microabscesses. As demonstrated in this case, follicular mucinosis can
be a presenting sign of rapidly progressive mycosis fungoides. In our review of
follicular mucinosis and its association with mycosis fungoides, we found that
the folliculotropic variant of mycosis fungoides appears more commonly to have an
aggressive course than classic mycosis fungoides.
PMID- 11004620
TI - A large-scale North American study of fungal isolates from nails: the frequency
of onychomycosis, fungal distribution, and antifungal susceptibility patterns.
AB - BACKGROUND: Onychomycosis, a fungal infection of the nail bed, is responsible for
up to 50% of nail disorders. Although several surveys have been conducted in
different parts of the world, there have been no multicenter epidemiologic
surveys of onychomycosis in North America. OBJECTIVE: A 12-center study was
undertaken to (1) determine the frequency of onychomycosis, (2) identify
organisms recovered from the nails, and (3) determine the antifungal
susceptibility of isolates. METHODS: A total of 1832 subjects participated in
this study and completed a comprehensive questionnaire, and nail clippings were
collected for potassium hydroxide examination and culturing. RESULTS: The
frequency of onychomycosis, as defined by the presence of septate hyphae on
direct microscopy and/or the recovery of a dermatophyte, was found to be 13.8%.
In general, the dermatophyte isolates were susceptible to the antifungals tested.
CONCLUSION: Because of the limited number of large-scale studies, the baseline
incidence is not firmly established. However, the higher frequency of
onychomycosis in this study may confirm the suspected increase in incidence of
disease in North America.
PMID- 11004621
TI - The prevalence of atopic dermatitis in Oregon schoolchildren.
AB - BACKGROUND: Although surveys from many parts of the world have shown that the
prevalence of atopic dermatitis (AD) in schoolchildren has increased greatly in
the past 40 years, there is no current prevalence information from the United
States. OBJECTIVE: Our objective was to investigate the utility of a recently
developed European questionnaire to estimate the prevalence of AD in urban and
rural Oregon schoolchildren. METHODS: The self-administered Schultz-Larsen
questionnaire (SLQ) of AD symptoms and history was completed by the parents of a
broad socioeconomic and ethnic mix of 5- to 9-year-old schoolchildren from 6
urban and 2 rural elementary schools in Oregon. Validation assessments included
comparisons of the questionnaire scores with clinical examination in a group of
age-matched children and with specific history components known to correlate with
AD. RESULTS: Data showed a prevalence of 17.2% using standard scoring criteria
for the SLQ and with a lower limit of 6.8% according to highly stringent criteria
derived from the validation study using dermatologic examination. A single
question ("Has a doctor ever said that your child has eczema?") was highly
concordant with the questionnaire determination, yielding very high predictive
accuracy (91.2%). CONCLUSION: This study of childhood AD frequency indicates a
high prevalence of AD in the United States, comparable to that recently observed
from studies in Europe and Japan. (J Am Acad Dermatol 2000;43:649-55.).
PMID- 11004622
TI - Photodamage pilot study: a double-blind, vehicle-controlled study to assess the
efficacy and safety of tazarotene 0.1% gel.
AB - BACKGROUND: Tazarotene, a potent acetylenic retinoid for topical use, might be
expected to benefit photodamaged skin, including improving the classical signs of
fine wrinkles, mottled hyperpigmentation, and roughness. OBJECTIVE: Our purpose
was to determine the efficacy and safety of tazarotene 0.1% gel in the treatment
of photodamaged dorsal forearm skin. METHODS: Ten healthy female volunteers, aged
45 to 65 years, with moderately photodamaged forearm skin applied tazarotene 0.1%
gel to one arm and vehicle gel to the other once daily for 12 weeks. The study
was a double-blind, randomized, paired-comparison evaluation conducted at a
single site. RESULTS: Tazarotene showed beneficial effects for several efficacy
variables. It was more efficacious than vehicle in reducing skin roughness and
fine wrinkling based on objective measurements. Tazarotene also corrected
epidermal atrophy and atypia and improved skin hydration properties. CONCLUSION:
In this 12-week pilot study tazarotene redressed abnormalities associated with
photo-damaged skin.
PMID- 11004623
TI - Basal cell carcinoma in chronic arsenicism occurring in Queensland, Australia,
after ingestion of an asthma medication.
AB - BACKGROUND: Ingestion of trivalent inorganic arsenic has long been recognized as
a cause of basal cell carcinomas (BCCs) and has been reported most often in
Taiwan and Singapore. OBJECTIVE: Our purpose was to study the clinical and
histologic characteristics of BCCs occurring in Australian Caucasians as a
consequence of chronic arsenicism due to ingestion of an arsenic-containing
medication. METHODS: Self-referred persons with a history of ingestion of Bell's
Asthma Medication were interviewed, and skin examinations were performed. Local
age- and sex-matched patients with BCCs were used to compare the distribution and
histologic subtypes of BCCs in arsenic-exposed and sporadic cases. RESULTS:
Thirty-six persons (21 male, 15 female; mean age, 57 years) participated, all of
whom had been exposed to the asthma medication early in life (mean age, 13 years)
for a mean duration of 5 years. Each person had at least one cutaneous sign of
chronic arsenicism, either self-reported or on examination, and all except one
had a history of either BCC or squamous cell carcinoma of the skin, with self
reports of 20 to 2000 skin lesions removed per person. The mean age at first
presentation with a BCC was 33 years, but neither latency nor number of skin
lesions appeared to be related to duration of exposure to arsenic. BCCs in
persons exposed to arsenic occurred more often on sun-protected sites compared
with BCCs in age- and sex-matched sporadic cases (P <.001), but the distribution
and histologic subtypes between these two groups were similar. CONCLUSION: We
have described BCCs in arsenic-exposed Australians and shown that they occur
predominantly in sun-protected locations. Although the reported number of skin
lesions is very high, the latency and number do not appear to be related to the
duration of arsenic exposure. The histologic types of the BCCs occurring in
arsenic-exposed persons are not different from sporadic BCCs.
PMID- 11004624
TI - Ultraviolet A1 (340-400 nm) phototherapy for scleroderma in systemic sclerosis.
AB - BACKGROUND: The presence of an inflammatory infiltrate consisting of helper T
cells and a dysregulated matrix metabolism leading to excessive deposition of
collagen are two pathogenetic factors responsible for the developments of
fibrosis and sclerosis in patients with systemic sclerosis. In previous studies,
ultraviolet A1 (UVA1) radiation phototherapy was shown to deplete skin
infiltrating T cells through the induction of T-cell apoptosis and to up-regulate
the expression of matrixmetalloproteinase-1 (collagenase-1) in dermal
fibroblasts. OBJECTIVE: Our purpose was to determine whether UVA1 phototherapy is
effective for systemic sclerosis. METHODS: Lesional skin on the forearms of
patients with systemic sclerosis (diffuse type, n =3; limited type, n =1) was
exposed to medium-dose UVA1 radiation (60 J/cm(2)) daily. RESULTS: In all
patients studied, UVA1 phototherapy-treated skin lesions were markedly softened
after 9 to 29 exposures. Clinical improvement was associated with an increase in
(1) joint passive range of motion values (P <.05), (2) skin temperature
(thermography, P <.05), and (3) cutaneous elasticity (cutaneous elastometry, P
<.05). Histologic evaluation of skin specimens obtained before and after UVA1
phototherapy revealed loosening of collagen bundles and the appearance of small
collagen fibers. CONCLUSION: These studies indicate that UVA1 phototherapy is
effective for patients with systemic sclerosis.
PMID- 11004625
TI - PUVA-cream photochemotherapy for the treatment of localized scleroderma.
AB - BACKGROUND: The efforts to treat localized scleroderma, including therapies with
potentially hazardous side effects, are often unsatisfactory. Recently, PUVA-bath
photochemotherapy has been proven highly effective in the treatment of localized
scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen (8-MOP)
containing cream or gel preparations, has been proven to be as effective as PUVA
bath therapy for palmoplantar dermatoses. OBJECTIVE: We sought to assess the
efficacy of PUVA-cream photochemotherapy in patients with localized scleroderma.
METHODS: Four patients with localized scleroderma were included in the study.
Diagnosis was confirmed by 20 MHz ultrasound assessment as well as pretreatment
skin biopsy specimens from lesional skin. PUVA-cream therapy was performed 4
times a week; all patients received 30 treatments. RESULTS: PUVA-cream
photochemotherapy induced significant clinical improvement or clearance of
localized scleroderma in all patients. Clearance was documented by clinical
features as well as by 20 MHz ultrasound and histopathologic analysis.
CONCLUSION: PUVA-cream phototherapy can be highly effective in patients with
localized scleroderma even if previous therapy was unsuccessful.
PMID- 11004626
TI - Peristomal dermatoses: a novel indication for topical steroid lotions.
AB - BACKGROUND: Dermatoses that interfere with the normal use of a stoma appliance
are common. When preventable causes, such as infection or allergy, are not
identified, barrier preparations or topical steroids have been used. However,
topical medicaments formulated in a cream or ointment base will cause stoma bags
to detach, resulting in leaks. OBJECTIVE: Our purpose was to investigate the
efficacy and suitability of corticosteroids in aqueous/alcohol lotions in the
management of peristomal dermatoses. METHODS: A clinic run by a dermatologist and
2 stoma nurses was created. Patients with a variety of noninfective, inflammatory
dermatoses were treated with topical corticosteroid lotions up to a maximum of 4
weeks, with occasional use thereafter in some cases. RESULTS: Topical,
aqueous/alcohol, corticosteroid lotions have been used in 60 patients and have
proved particularly useful for the treatment of irritant dermatitis, pyoderma
gangrenosum, psoriasis, and constitutional eczema. After the initial treatment
course, occasional applications, approximately every 2 weeks, may be necessary to
control the skin disorder. This low frequency of application minimizes the risk
of side effects so that we have not identified local or systemic side effects in
any of the patients treated so far. CONCLUSION: Topical corticosteroids
formulated in aqueous alcohol lotion are effective and acceptable treatments for
peristomal dermatoses. If used appropriately, the risk of side effects is low.
PMID- 11004628
TI - Silicone auricular prosthesis.
AB - Skin cancer surgery of the ear may result in a large defect of skin and cartilage
requiring a staged flap procedure for reconstruction. An alternative to surgical
reconstruction is the creation of a silicone auricular prosthesis. These
prostheses provide a cost-effective and cosmetically acceptable means of
camouflage for patients who decline or postpone surgical reconstruction. The
process of creating a silicone auricular prosthesis is discussed.
PMID- 11004627
TI - Therapeutic update: use of risperidone for the treatment of monosymptomatic
hypochondriacal psychosis.
AB - Monosymptomatic hypochondriacal psychoses such as delusions of parasitosis are
often difficult to treat. For the past two decades, pimozide has been considered
the drug of choice. Although a few controlled studies have been done to support
the efficacy of pimozide, the recommendation of treatment of choice is largely
based on case reports. Pimozide has significant side effects, including cardiac
and extrapyramidal abnormalities, which are of most concern in the treatment of
the elderly. Although pimozide does appear to be effective in some cases of
somatic delusional disorders, newer antipsychotics such as risperidone have also
been shown to be beneficial in treating this perplexing cluster of disorders.
Risperidone is generally considered safer than pimozide and should be considered
as first-line therapy for monosymptomatic hypochondriacal psychoses.
PMID- 11004629
TI - Potassium iodide in dermatology: a 19th century drug for the 21st century-uses,
pharmacology, adverse effects, and contraindications.
AB - Potassium iodide (KI) is a useful drug in the dermatologic armamentarium. It is
successfully used for inflammatory dermatoses, most notably erythema nodosum,
subacute nodular migratory panniculitis, nodular vasculitis, erythema multiforme,
and Sweet's syndrome. KI is also successfully used for cutaneous and
lymphocutaneous sporotrichosis. The precise mechanism by which KI acts is
unknown. Although many minor side effects are common with this drug, major side
effects can occur in pregnant patients and those with a history of kidney or
thyroid disease. This article reviews the pharmacology, mechanism of action,
indications, contraindications, and adverse effects of KI as a therapeutic agent.
PMID- 11004630
TI - Widespread cutaneous vascular papules associated with peripheral blood
eosinophilia and prominent inguinal lymphadenopathy.
AB - A new section entitled "Dermatology Grand Rounds at the NIH" appears this month.
The idea behind it is to provide a unique look at instructive dermatologic cases
being presented at the weekly Dermatology Branch Grand Rounds at the National
Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland.
Patients seen at the NIH Clinical Center (which includes the NIH inpatient wards
and outpatient clinics) are indeed unusual. To be evaluated here, they must be
referred by an outside physician and must be placed in a research protocol. In
other words, by this criterion, all NIH patients are considered research
subjects. The diseases studied at the NIH range from the common to the obscure.
Similarly, the dermatologic manifestations of these diseases are equally as
diverse. Thus the purpose of this new section is to share some of these
fascinating cases with the dermatologic community at large, as well as to provide
a glimpse of exciting translational research that has relevance to clinical
dermatologists. The format will be simple. Cases will be presented as unknowns,
including relevant results from the history, physical examination, and
histopathologic analyses. This will be done to challenge the clinicopathologic
skills of the readers; authors will make every attempt to make the color clinical
and pathologic photographs of the highest quality possible to assist readers in
making the correct diagnoses. The discussion will be brief, focusing on the key
teaching points of each case. These teaching points will vary from cases to case,
covering clinical and histologic information, treatment issues, and/or novel
laboratory advances with clinical relevance. Authors will emphasize brevity and
clarity in all subsections of the case report, which I hope will promote a good
learning experience for dermatology residents and busy practitioners alike. This
section will initially be published 4 times annually. Finally, because the
section is new to the JAAD, I welcome comments and suggestions to improve the
quality of the articles.-Andrew Blauvelt, MD Feature Editor
PMID- 11004631
TI - Pilomatricomas contain activating mutations in beta-catenin.
PMID- 11004632
TI - Directional migration of human keratinocytes in direct current electric fields
requires growth factors and calcium and is regulated by epidermal growth factor
receptor.
PMID- 11004633
TI - Endothelin-1 down-regulates E-cadherin in melanocytic cells by apoptosis
independent activation of caspase-8.
PMID- 11004634
TI - The histopathologic misdiagnosis of melanoma: sources and consequences of "false
positives" and "false negatives".
PMID- 11004635
TI - Identifying the missing link between UV and p53: the role of phosphatidyl
inositol kinase-related kinases.
PMID- 11004636
TI - The use of interferon alfa as adjuvant therapy for advanced cutaneous melanoma:
the need for more evidence.
AB - Interferon alfa is rapidly gaining acceptance as the standard of care for
patients with advanced but nonmetastatic cutaneous malignant melanoma. The
randomized trials of interferons for melanoma are reviewed with attention to any
survival benefits demonstrated by these studies. Because none of these studies
are placebo controlled, questions regarding the placebo effects interferons may
possess are addressed, as is an analogous clinical scenario in which interferons
appeared to be beneficial in nonplacebo controlled trials but were shown to be
ineffective in placebo-controlled trials. Moreover, given the significant
toxicities and financial costs of interferons, the argument is advanced that
interferon alfa should not become the standard of care for melanomas until the
results of randomized, placebo-controlled trials evaluating the survival
advantages of interferon alfa for melanoma become available.
PMID- 11004637
TI - Surgical pearl: digital imaging for mapping Mohs surgical specimens.
PMID- 11004638
TI - Paraneoplastic pemphigus with circulating antibodies directed exclusively against
the pemphigus vulgaris antigen desmoglein 3.
AB - A patient with follicular B-cell lymphoma presented with erythroderma associated
with cutaneous and mucosal blisters. Histologic and direct immunofluorescence
analysis of lesional skin showed a typical pattern of paraneoplastic pemphigus
(PNP). Interestingly, indirect immunofluorescence on rat bladder was negative and
immunoblot analysis of the patient's serum on epidermal extracts demonstrated
antiepidermal antibodies that only recognized the pemphigus vulgaris antigen
desmoglein 3, with no antibodies directed against the different proteins of the
plakin family. To our knowledge this has never been reported in the literature.
It exemplifies the overlap between pemphigus vulgaris and PNP and the pathogenic
role of anti-desmoglein 3 antibodies in PNP. Moreover, it underscores the need to
consider clinical, histologic, and immunologic features for the diagnosis of PNP.
PMID- 11004639
TI - Constipation presenting as recurrent vulvovaginitis in prepubertal children.
AB - Vulvovaginitis is the most common gynecologic problem in premenarcheal girls. We
describe 3 patients with recurrent vulvovaginitis caused by bacterial infection
who responded to treatment of constipation with resolution of the vulvovaginitis.
There were no recurrences during the follow-up period of 15 to 36 months. We
propose that underlying constipation should be added to the list of possible
causes of recurrent vulvovaginitis.
PMID- 11004640
TI - Disseminated superficial actinic porokeratosis associated with topical PUVA.
AB - Disseminated superficial actinic porokeratosis (DSAP) is associated with sun
exposure and tanning bed usage and has been rarely reported in association with
systemic PUVA. We report the first case of DSAP occurring after topical foot
PUVA.
PMID- 11004641
TI - Dermoscopic features of cutaneous local recurrent melanoma.
AB - We describe for the first time the dermoscopic features of cutaneous recurrent
melanoma including a globular pattern and a diffuse nonhomogeneous pigmentation.
These findings greatly differ from those observed in primary cutaneous melanoma
and should be considered in the dermoscopic differential diagnosis of pigmented
skin lesions.
PMID- 11004642
TI - Photochemotherapy for systemic and localized scleroderma.
PMID- 11004643
TI - Evidence-based medicine: the epistemology that isn't.
PMID- 11004644
TI - Paradoxical effect of interferon alfa on lichen myxedematosus.
PMID- 11004645
TI - Pruritic urticarial papules and plaques of pregnancy and multiple pregnancies.
PMID- 11004646
TI - Long latency of human herpesvirus type 8 infection and the appearance of classic
Kaposi's sarcoma.
PMID- 11004648
TI - Neurophysiologic response to intraoperative lumbosacral spinal manipulation.
AB - BACKGROUND: Although the mechanisms of spinal manipulation are poorly understood,
the clinical effects are thought to be related to mechanical, neurophysiologic,
and reflexogenic processes. Animal studies have identified mechanosensitive
afferents in animals, and clinical studies in human beings have measured
neuromuscular responses to spinal manipulation. Few, if any, studies have
identified the basic neurophysiologic mechanisms of spinal manipulation in human
beings or animals. OBJECTIVES: The purpose of this clinical investigation was to
determine the feasibility of obtaining intraoperative neurophysiologic recordings
and to quantify mixed-nerve root action potentials in response to lumbosacral
spinal manipulation in a human subject undergoing lumbar spinal surgery. METHODS:
An L4-L5 laminectomy was performed in a 62-year-old man. Short-duration (<0.1 ms)
mechanical force, manually assisted spinal manipulative thrusts (150 N) were
delivered to the lumbosacral spine with an Activator II Adjusting Instrument.
With the spine exposed, spinal manipulative thrusts were delivered internally to
the L5 mammillary process, L5-S1 joint, and the sacral base with various force
vectors. This protocol was repeated by contacting the skin overlying respective
anatomic landmarks. Mixed-nerve root recordings were obtained from gas-sterilized
platinum bipolar hooked electrodes attached to the S1 nerve root at the level of
the dorsal root ganglion during the spinal manipulative thrusts and during a 30
second baseline period during which no spinal manipulative thrusts were applied.
RESULTS: During the active trials, mixed-nerve root action potentials were
observed in response to both internal and external spinal manipulative thrusts.
Differences in the amplitude and discharge frequency were noted in response to
varying segmental contact points and force vectors, and similarities were noted
for internally and externally applied spinal manipulative thrusts. Amplitudes of
mixed-nerve root action potentials ranged from 200 to 2600 mV for internal
thrusts and 800 to 3500 mV for external thrusts. CONCLUSIONS: Monitoring mixed
nerve root discharges in response to spinal manipulative thrusts in vivo in human
subjects undergoing lumbar surgery is feasible. Neurophysiologic responses
appeared sensitive to the contact point and applied force vector of the spinal
manipulative thrust. Further study of the neurophysiologic mechanisms of spinal
manipulation in humans and animals is needed to more precisely identify the
mechanisms and neural pathways involved.
PMID- 11004649
TI - Do cerebral potentials to magnetic stimulation of paraspinal muscles reflect
changes in palpable muscle spasm, low back pain, and activity scores?
AB - OBJECTIVE: Previous studies have shown that cortical-evoked potentials on
magnetic stimulation of muscles are influenced by muscle contraction, vibration,
and muscle spasm. This study was carried out to determine whether these
potentials correlate with palpatory muscle spasm, patient symptoms, and
disability in patients with low back pain. METHODS: A prospective observational
study was performed on 13 subjects with a history of low back pain visiting an
orthopedic hospital-based clinic. Patients were screened for serious pathologic
conditions by an orthopedic surgeon. The patients were then evaluated for the
presence of muscle spasm by one of the investigators who was blinded to the
results of the evoked potential studies. Patients were asked to complete a low
back pain visual analogue scale (VAS) and a Roland-Morris Activity Scale (RMAS).
Cortical-evoked potentials were recorded with a magnetic stimulator placed over
the lumbar paraspinal muscles with the patient in the prone position. The
palpatory examination, VAS, RMAS, and the cortical potentials were repeated after
2 weeks of therapy commonly used to reduce muscle spasm. RESULTS: The patients
demonstrated a significant decrease in low back pain VAS and RMAS scores after
treatment compared with before treatment. There was a reduction in the amount of
palpatory muscle spasm in 11 of 13 cases. The cortical potentials before
treatment were attenuated compared with previously reported controls and showed a
significant increase before and after treatment in the amplitude of these
potentials with multivariate analysis of variance. There was significant
correlation between the changes in cortical potentials after treatment and the
changes noted in paraspinal muscle spasm and VAS and RMAS scores. CONCLUSIONS:
This study confirms the previous report that the amplitude of cerebral-evoked
potentials on magnetic stimulation of paraspinal muscles is depressed in the
presence of palpable muscle spasm. The close correlation among these potentials,
paraspinal muscle spasm, and clinical symptoms suggests that the measurement of
muscle activity may be more important in the assessment of low back pain than is
commonly accepted.
PMID- 11004650
TI - Short-term effects of cervical manipulation on edge light pupil cycle time: a
pilot study.
AB - BACKGROUND: Edge light pupil cycle time (ELPCT) is one of the eye's light
reflexes. Studies have shown ELPCT to be a measurable constant, unaffected by
visual acuity, refractive error, eye color, pupil size, or sex. Control of this
reflex occurs through the autonomic nervous system. Various authors suggest that
spinal manipulative techniques can produce distant effects mediated in part by
alterations in autonomic tone after intervention. OBJECTIVE: To investigate the
effects of a C1-2 high-velocity, low-amplitude manipulation on ELPCT. DESIGN: A
single-group, randomized pilot study without a control group. METHODS: Thirteen
men (mean age 24.2 years) without a history of eye disease or central or
autonomic nervous system pathologic conditions had their ELPCT measured before
and after manipulation. The manipulation comprised a high-velocity, low-amplitude
rotatory thrust, localized to the C1-2 joint on the left (n = 6) or right (n = 7)
eye, determined randomly. RESULTS: ELPCT measures demonstrated a significant
difference for both eyes before and after manipulation (P = .002; the right eye,
P = .027; the left eye, P = .046). CONCLUSION: This suggests that ELPCT, which is
mediated through the autonomic nervous system, can be directly influenced by high
velocity manipulation to the upper cervical spine.
PMID- 11004651
TI - MRI of the spine and spinal cord: imaging techniques, normal anatomy, artifacts,
and pitfalls.
AB - BACKGROUND: Magnetic resonance imaging (MRI) is widely used to evaluate the spine
and spinal cord. OBJECTIVE: In this article, MRI of the spine is discussed in
terms of normal anatomy, standard and advanced imaging techniques, general
indications, limitations, and potential for the future. DISCUSSION: Although MRI
does not provide the high bony detail possible with computed tomography, the
appropriate combination of the sequences takes advantage of the different tissue
characteristics to discriminate the various bony-and soft-tissue structures of
the spine. CONCLUSION: MRI enables the imaging specialist to evaluate a large
anatomic region in multiple planes and can better examine the spinal cord.
PMID- 11004652
TI - Chiropractic biophysics digitized radiographic mensuration analysis of the
anteroposterior cervicothoracic view: a reliability study.
AB - OBJECTIVE: To investigate the reliability of a radiographic measurement procedure
that uses a computer and sonic digitizer to determine projected spinal
displacements from an ideal, normal position. DESIGN: A blind, repeated-measure
design was used. Anteroposterior cervicothoracic spine radiographs were presented
in random order to each of 3 examiners. Each film was digitized, and the films
were randomized for a second examination. SETTING: Private, primary care
chiropractic clinic. MAIN OUTCOME MEASURES: Intraclass correlation coefficients
for intraexaminer and interexaminer reliability for measures on radiographs
comparing the perpendicular distance (T(x)) from a vertical axis line drawn
through the center of T4 and the center of C2, the linear distance
(vertebra(apex)) from the center of the vertebra most displaced from a line
connecting the centers of C2 and T4, the angle (Rz) formed by the intersection of
the vertical axis line and the upper thoracic line, and the angle of intersection
(CDA) between the upper thoracic line and the cervical line. RESULTS:
Intraexaminer reliability for T(x) distance was 0.99 to 1.00, with confidence
intervals from 0.98-1.00; for vertebra(apex) was 0.96 to 0.97, with confidence
intervals from 0.92-0.98; for Rz was 0.94 to 0.98, with confidence intervals from
0. 89-0.99; and for CDA was 0.92 to 0.95, with confidence intervals from 0.84
0.97. Interexaminer reliabilities for the 3 examiners ranged from 0.97 to 0.99.
CONCLUSIONS: Measures similar to those described in this study are commonly used
to quantify and categorize spinal displacements from true vertical alignment
(i.e., scoliosis measurements). Intraclass correlation coefficient values >0.70
are considered accurate enough for use in clinical and research applications. The
measures tested here would fit within these guidelines of reliability.
Establishing reliability is an important first step in evaluating these measures
so that future studies of validity may be undertaken.
PMID- 11004653
TI - Lumbosacral transitional segments: classification, prevalence, and effect on disk
height.
AB - OBJECTIVE: To determine the rate of lumbosacral transitional segments among
chiropractic practice settings and to determine if this anomaly would affect the
height of the lumbosacral disk. STUDY DESIGN: Retrospective review of
radiographs. SETTING: Los Angeles College of Chiropractic outpatient clinic and a
private chiropractic office. SAMPLES: A total of 20 lumbar series with
lumbosacral transitional segments from a private chiropractic office, 47 lumbar
series with lumbosacral transitional segments, and 60 age- and sex-matched
control series from a college clinic. RESULTS: A total of 2.3% of 882 lumbar
series at the private chiropractic office and 6.5% of 786 lumbar series at the
Whittier Health Center showed lumbosacral transitional segments of types II, III,
or IV. The L5-S1 intervertebral disk height was significantly smaller in patients
with lumbosacral transitional segments compared with those without (ie, 11% vs
19% of total lumbar disk height, respectively). When bilateral bony fusion of L5
to the sacrum was present, the L5-S1 disk height was significantly smaller than
that without bony fusion (ie, 8% vs. 12% to 14% of total lumbar disk height,
respectively). CONCLUSIONS: We conclude that the rate of occurrence of
lumbosacral transitional segments is low in chiropractic practice. In the
presence of lumbosacral transitional segments, especially when there was bony
fusion, the lumbosacral intervertebral disk was significantly narrower than the
upper lumbar disks, which should not be considered as disk degeneration or
displacement. The type of lumbosacral transitional segment present also showed a
significant effect on the height of the lumbosacral disk.
PMID- 11004654
TI - Complex regional pain syndrome and chiropractic.
AB - OBJECTIVE: Complex regional pain syndromes (CRPS) represent curious and difficult
syndromes for both patient and clinician. CRPS presents as a triad of signs and
symptoms, usually after a seemingly trivial injury to a peripheral joint or
appendage. The clinical triad includes severe pain, vasomotor changes in and
around the affected area, and trophic changes in the affected limb. Many of the
acute symptoms are similar to those seen after many acute injuries, which makes
an early diagnosis often times difficult. Current treatment protocols revolve
around aggressive physical therapy plus pharmacologic interventions aimed at
limiting sympathetic nervous system activity. OBJECTIVE: To review the literature
on CRPS regarding symptoms, diagnosis, treatment, and causal mechanisms and to
discuss alternative treatment approaches and the possible role of chiropractic
care in patient rehabilitation. DATA SOURCES: Texts, review articles, and
randomized clinical trials investigating treatments, causes, and epidemiology.
CONCLUSIONS: Recent research calls into question the predominant theories that
view excessive sympathetic nervous system activity as the cause of CRPS. No
evidence of an increase in sympathetic nervous system activity has been found,
and new theories suggest that an increase in the sensitivity of neurotransmitter
receptors may be the cause of CRPS. Alternatively, other research has suggested
that a local inflammatory process may in fact cause CRPS. Although no research
has been completed examining the role of chiropractic care in the treatment of
CRPS, there is reason to believe that spinal manipulation may be beneficial to
patients with CRPS.
PMID- 11004655
TI - Clinical considerations in the chiropractic management of the patient with Marfan
syndrome.
AB - OBJECTIVE: To describe the chiropractic management of a patient with whiplash
associated disorder and a covert, concomitant dissecting aneurysm of the thoracic
aorta caused by Marfan syndrome or a related variant. CLINICAL FEATURES: A 25
year-old man was referred by his family physician for chiropractic assessment and
treatment of neck injuries received in a motor vehicle accident. After history,
physical examination, and plain film radiographic investigation, a diagnosis of
whiplash-associated disorder grade I was generated. INTERVENTION AND OUTCOME: The
whiplash-associated disorder grade I was treated conservatively. Therapeutic
management involved soft-tissue therapy to the suspensory and paraspinal
musculature of the upper back and neck. Rotary, manual-style manipulative therapy
of the cervical and compressive manipulative therapy of the thoracic spinal
column were implemented to maintain range of motion and decrease pain. The
patient achieved full recovery within a 3-week treatment period and was
discharged from care. One week after discharge, he underwent a routine evaluation
by his family physician, where an aortic murmur was identified. Diagnostic
ultrasound revealed a dissecting aneurysm measuring 78 mm at the aortic root.
Immediate surgical correction was initiated with a polyethylene terephthalate
fiber graft. The pathologic report indicated that aortic features were consistent
with an old (healed) aortic dissection. There was no evidence of acute
dissection. Six month follow-up revealed that surgical repair was successful in
arresting further aortic dissection. CONCLUSION: The patient had an old aortic
dissection that pre-dated the chiropractic treatment (which included manipulative
therapy) for the whiplash-associated disorder. Manipulative therapy, long
considered an absolute contraindication for abdominal and aortic aneurysms, did
not provoke the progression of the aortic dissection or other negative sequelae.
The cause, histology, clinical features, and management considerations in the
treatment of this patient's condition(s) are discussed.
PMID- 11004656
TI - Residency programs at the Canadian Memorial Chiropractic College.
PMID- 11004657
TI - Reflex effects of vertebral subluxations: the peripheral nervous system. An
update.
PMID- 11004658
TI - Reflex effects of vertebral subluxations: the peripheral nervous system. An
update
PMID- 11004659
TI - Motion palpation: it's time to accept the evidence.
PMID- 11004660
TI - Motion palpation: It's time to accept the evidence
PMID- 11004661
TI - A new era of cancer research: cutting and pasting of chromosomes.
PMID- 11004662
TI - K-ras point mutation is associated with enhancement by deoxycholic acid of colon
carcinogenesis induced by azoxymethane, but not with its attenuation by all-trans
retinoic acid.
AB - The effects of deoxycholic acid (DCA) with and without all-trans-retinoic acid
(ATRA) on the incidence of colon tumors induced by azoxymethane, the incidence of
K-ras point mutation in colon tumors and the labeling index of colon mucosa were
investigated in male Wistar rats. Rats received 5 weekly injections of 7.4 mg/kg
body weight of azoxymethane. From the start of the experiment, all rats in 3
groups also received chow pellets containing 0.3% DCA with and without s.c.
injections of 0.75 or 1.5 mg/kg body weight of ATRA every other day until the end
of week 45. Oral administration of DCA significantly increased the incidence of
colon tumors in week 45. Concomitant use of DCA and ATRA at either dose
significantly attenuated the enhancement by DCA of colon tumorigenesis.
Administration of DCA significantly increased the incidence of K-ras point
mutation in colon tumors and the labeling index in the colon mucosa. Combined
administration of DCA and ATRA significantly reduced the labeling index of colon
mucosa, which was increased by DCA, but did not affect the incidence of K-ras
point mutation in colon tumors. These findings suggest that DCA enhances
development of colon tumors and that this enhancement is attenuated by ATRA. A
possible mechanism of this enhancement is induction of K-ras point mutation.
However, decreased cell proliferation in the colon mucosa may be closely related
to the attenuation of DCA-enhanced colon tumorigenesis, but not suppression of K
ras point mutation.
PMID- 11004663
TI - Tumor-derived p53 mutant C174Y is a gain-of-function mutant which activates the
fos promoter and enhances colony formation.
AB - SV40 large T antigen-induced primitive neuroectodermal tumors of the rat provide
a model system to study induction and progression of primitive neuroectodermal
tumors at the molecular level. A cell line derived from such a tumor reproducibly
gave rise to malignant derivatives that ceased large T-antigen expression but
harbored a mutant p53 allele with a common mutation at Cys(174) to Tyr (C174Y).
To determine whether this p53 mutation contributes to tumor progression, we
analyzed mutant C174Y functionally. Co-transfection experiments in Saos-2 cells
with mutant or wild-type p53 and reporter genes linked to various p53-responsive
promoters revealed that mutant C174Y failed to transcriptionally transactivate
the Mdm2, Waf1, Cyclin G and Bax promoters. Loss of transcriptional activation
correlated with loss of DNA-binding activity. Moreover, mutant C174Y exhibited a
dominant negative effect on co-expressed wild-type p53. The ability of mutant p53
to repress the viral RSV, LTR or SV40 early promoters or the cellular fos
promoter was likewise impaired. In contrast, it showed even induction of the fos
promoter. Consistent with these observations, mutant C174Y was non-functional in
the suppression of Saos-2 cell growth and even conferred a growth advantage to
the cells. Surprisingly, mutant C174Y was also impaired in nuclear transport, as
revealed by immunofluorescence analyses. Taken together, our results demonstrate
that mutant C174Y possesses features that can positively contribute to cancer
progression.
PMID- 11004664
TI - Gene expression of neuronal nitric oxide synthase and adrenomedullin in human
neuroblastoma using real-time PCR.
AB - The objective of our study was to assess the gene expression of the
antiproliferative systems neuronal nitric oxide synthase (nNOS) and
adrenomedullin (AM) in human neuroblastoma. A novel real-time PCR method was
evaluated using neuropeptide Y (NPY) for validation. Glyceraldehyd-3-phospate
dehydrogenase (GAPDH) and NPY gene expression in neuroblastomas of 50 patients
were measured in parallel by competitive quantitative and TaqMan real-time RT
PCR. AM and nNOS mRNA were determined by real-time PCR. Our results showed a
linear relationship between competitive quantitative and real-time RT-PCR
measurements of NPY and GAPDH (r = 0.87 and r = 0.92, respectively). AM and nNOS
mRNA was found in all tumor samples. AM/GAPDH mRNA increased with higher
differentiation according to Shimada (p = 0.013). There was no relation between
MYCN amplification nor with the tumor stage (p = 0.78 and p = 0.30,
respectively). AM/GAPDH did not relate to recurrence or death in a 5-year follow
up period. Neuronal NOS/GAPDH expression did not relate to any biological or
clinical parameter of prognosis or differentiation. Similar results were obtained
when the neuronal marker protein gene product 9.5 (PGP9.5) was used to normalize
mRNA concentration. In conclusion, TaqMan real-time PCR appears to be a reliable
method to quantify gene expression in neuroblastomas. Adrenomedullin mRNA in
neuroblastoma is linked to tumor differentiation but not to prognostic markers.
PMID- 11004665
TI - Selective activation of the fatty acid synthesis pathway in human prostate
cancer.
AB - A substantial subset of breast, colorectal, ovarian, endometrial and prostatic
cancers displays markedly elevated expression of immunohistochemically detectable
fatty acid synthase, a feature that has been associated with poor prognosis and
that may be exploited in anti-neoplastic therapy. Here, using an RNA array
hybridisation technique complemented by in situ hybridisation, we report that in
prostate cancer fatty acid synthase expression is up-regulated at the mRNA level
together with other enzymes of the same metabolic pathway. Contrary to the
observations that in many cell systems (including androgen-stimulated LNCaP
prostate cancer cells) fatty acid and cholesterol metabolism are co-ordinately
regulated so as to supply balanced amounts of lipids for membrane biosynthesis,
storage or secretion, no changes in the expression of genes involved in
cholesterol synthesis were found. These findings point to selective activation of
the fatty acid synthesis pathway and suggest a shift in the balance of lipogenic
gene expression in a subgroup of prostate cancers.
PMID- 11004666
TI - Alterations in the gene expression profile of MCF-7 breast tumor cells in
response to c-Jun.
AB - MCF7 breast tumor cells overexpressing human c-Jun exhibit a transformed
phenotype characterized not only by increased tumorigenicity but also by enhanced
motility and invasion. The cellular phenotypic response to c-Jun overexpression
is likely due, at least in part, to altered patterns of gene expression. In order
to begin to understand the complexities by which elevated production of c-Jun
alters the state of the cell, we have profiled the expression of 588 different
genes by comparative hybridization. By using this approach, we have identified a
total of 21 upregulated or downregulated gene targets responsive to c-Jun
overexpression. Interestingly, 8 of these genes have been previously found
associated with c-Jun or AP-1 activity and therefore provide internal validation
for this approach to target gene discovery. The remaining 13 genes represent
potential new c-Jun regulated target genes. Genomic sequence information was
available for 15 of the 21 genes identified in this screen. Analysis of these
genomic sequences revealed the presence of AP-1 or AP-1-like sequences in 12 of
the 15 genes examined. Consistent with a direct mechanism of target regulation by
c-Jun, gel shift analysis of selected AP-1-containing promoter regions revealed
elevated and specific binding by proteins present in nuclear extracts of c-Jun
expressing MCF7 cells.
PMID- 11004667
TI - p53-dependent induction of heat shock protein 27 (HSP27) expression.
AB - Transcriptional activation of the p53 target genes plays a critical role in the
cellular response to DNA damage, hypoxia, cellular stress and other signals
regulating the cell cycle and apoptosis. The discovery of new p53 target genes
continues to reveal novel mechanisms of action of this multifaceted protein. We
used cDNA arrays to search for p53-regulated genes in prostate cancer cells. In
this report, we describe robust induction of heat shock protein 27 (hsp27) in
prostate cancer cells (DU145, LNCaP, PC3) following wild-type p53 expression from
an adenoviral p53 expression vector (AdWTp53). A mutant p53 (R175H)-containing
adenoviral expression vector did not induce hsp27. hsp27 expression was not
altered in prostate cancer cells following expression of cyclin-dependent kinase
inhibitors: p21(waf1/cip1) and p27(kip1) from adenoviral expression vectors.
Treatment of cells with staurosporine, an apoptosis-inducing agent, did no affect
hsp27 expression. These observations provide evidence that induction of hsp27
expression was wild-type p53-specific and was not due to non-specific effects of
cell growth arrest and/or apoptosis. Previous studies and the experiment reported
here show induction of hsp27 expression in response to androgen ablation, a
physiological state that induces apoptosis in prostatic epithelial cells. The
nature of p53 and hsp27 interactions in the regulation of apoptosis and/or cell
growth needs to be further defined.
PMID- 11004668
TI - Protein kinase C isoforms involved in regulation of cell shape and locomotion of
human fibrosarcoma HT1080 cells.
AB - The role of protein kinase C (PKC) isoforms in the regulation of cell shape
[switch between fibroblast-like and crescent shape (CS)] and of locomotion of
human fibrosarcoma HT1080 cells has been investigated. The PKC activator phorbol
myristate acetate (PMA) induced the transition of elongated fibroblast-like cells
into CS cells and stimulated locomotion. Both responses to PMA were inhibited by
the PKC inhibitor Ro 31-8220. Analysis of the time course showed that stimulation
of shape changes (formation of CS cells) and locomotor activity (increase in the
proportion and speed of locomoting cells) was maximal in the early phase of the
response (up to 2.5 hr) and significantly decreased later (15 to 21 hr). CS
formation and stimulated locomotion correlated closely with a marked
redistribution from the cytosol to the membrane of PKC isoforms alpha, beta1 and
gamma in the early phase (0.5 to 2 hr) following activation with PMA. The
subsequent reduction of the proportion of CS cells and of cell locomotion
correlated with down-regulation of these isoforms in the second phase (16 to 21
hr). In contrast, the total amount and distribution of PKC beta2 remained almost
unchanged with 10(-8) M PMA up to 21 hr. Furthermore, changes in shape and
locomotion did not correlate with the responses of PKC delta to PMA. Inhibition
of PMA-stimulated locomotion by the more specific inhibitor Go 6976 is consistent
with a role of PKC alpha and beta1 in this response. Ro 31-8220 alone induced a
moderate down-regulation of PKC isoforms alpha and delta, but it also inhibited
the more pronounced down-regulation of these isoforms by PMA. Our results
indicate that activation of PKC isoforms alpha, gamma and beta1, but not beta2 or
delta, stimulates locomotion and formation of CS cells in human fibrosarcoma
HT1080 cells.
PMID- 11004669
TI - Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological
attributes of sporadic breast cancer.
AB - Germline mutations in the breast cancer-associated genes BRCA1 and BRCA2 confer a
lifetime risk of malignancy. Distinctive morphological features have been
attributed to these familial tumours; however, in sporadic breast cancer, the
inter-relationship between loss of heterozygosity (LOH) of these loci and tumour
morphology remains to be fully elucidated. We studied a series of 120 sporadic
breast carcinomas using microsatellite markers to identify LOH of BRCA1, BRCA2,
p53 and PTEN. The associations between loss at each of the loci were examined and
related to tumour morphology. LOH of the 4 loci did not occur independently;
there were highly significant associations between LOH of BRCA1 and both BRCA2 (p
< 0.001) and p53 (p < 0.001). LOH at all 4 loci was significantly associated with
a high degree of nuclear pleomorphism. Tumours with LOH of BRCA1 also had high
mitotic indices, few tubules and a paucity of DCIS, all of which are
morphological features similar to those described for familial cases. Following
Bonferroni's correction for multiple tests, we found that the tumours with LOH of
BRCA1 were still significantly associated with a high mitotic index (p = 0.0006)
and a high degree of nuclear pleomorphism (p = 0.001).
PMID- 11004670
TI - Variant estrogen receptor alpha mRNAs in human breast cancer specimens.
AB - A panel of human breast cancer specimens was examined for single base change
mutations by DNA sequencing and for larger deletions using a PCR-based assay. In
the cancer specimens examined, no sequencing variants were detected other than a
previously characterized polymorphism. Although most of the specimens contained
estrogen receptor (ER) variants at a low level, 2 of 118 specimens exhibited
variants which, after amplification, constituted most of the amplified ER cDNA.
One specimen contained a single variant form, and there was little evidence of
the wild-type ER mRNA by PCR, Northern blotting or immunocytochemistry. The
second specimen, despite the presence of a normal-sized mRNA by Northern blotting
and normal immunocytochemical staining for ER, contained at least 5 different
variant forms as well as the wild-type ER. All but 1 of the variant forms were
processing variants, and 3 of these processing variants have not been described
before. One variant, although lacking exons 2-4, has break points in exons 1 and
5 that do not correspond to intron-exon boundaries. This variant might reflect
more widespread damage to the genome in this breast cancer specimen. The low
level of occurrence of variants suggests that ER variant forms, at least in the
coding region, do not contribute generally to the progression of breast cancer.
PMID- 11004671
TI - Primary cervical carcinomas show 2 common regions of deletion at 3P, 1 within the
FHIT gene: evaluation of allelic imbalance at FHIT, RB1 and TP53 in relation to
survival.
AB - Chromosome arm 3p is re-arranged in many tumor types, including cervical
carcinomas. Putative tumor-suppressor genes on 3p have been proposed, including
the FHIT gene, which maps to chromosome band 3p14.2. We have analyzed 79 primary
cervical carcinomas for allelic imbalance (AI) at 17 chromosome 3 loci, including
3 within the FHIT gene. Expression of the FHIT gene was evaluated after
immunohistochemistry with an antibody against the pFHIT protein. Previously
determined human papillomavirus status, defined after in situ hybridization,
showed type 16 or 18 in 56/77 tumors. Tumors were also analyzed for AI at loci
within the RB1 (chromosome band 13q14.2) and the TP53 (17p13) genes for AI. AI
was found at 1 or more 3p loci in 50/79 tumors, at frequencies ranging from 30%
to 52% at the individual loci. Two smallest regions of overlapping deletion
(SROs) were found, 1 including parts of the FHIT gene (SRO flanked by D3S1481 and
D3S1313) and another more distal SRO between D3S32 and D3S1286. FHIT protein
expression was reduced in 57/69 (83%) tumors but not associated with AI at FHIT
loci (p = 0.56). AI was found in TP53 and RB1 in 18% and 29% of the samples,
respectively. Relapse-free survival was associated with AI in the TP53 gene in
both a univariate (p = 0.0003) and a multivariate (p = 0.004) analysis. This
study confirms a high frequency of AI at chromosome arm 3p in primary cervical
carcinomas. The AI results and the reduced FHIT protein staining indicate that
FHIT alterations are important in cervical carcinogenesis.
PMID- 11004672
TI - TP53 mutations and MDM2 gene amplification in squamous-cell carcinomas of the
esophagus in south Thailand.
AB - Squamous-cell carcinoma of the esophagus (SCCE) shows geographic variations in
incidence that are thought to reflect the etiological involvement of
environmental or dietary risk factors. Mutations of TP53 are frequent in SCCE,
and there is evidence that both the frequency and type of these mutations may
differ from one geographic area to the other. Although SCCE is relatively rare in
most parts of Thailand, the province of Songkhla (south Thailand) has been
described as a high-risk area for SCCE. We have analyzed 56 SCCE cases from this
area for TP53 mutations by denaturing gradient gel electrophoresis (DGGE, exons 5
8) and direct DNA sequencing. The same tumors were also analyzed for MDM2 gene
amplification by differential PCR. TP53 mutations were detected in 23 cases
(41%). In contrast, clear amplification of MDM2 was detected in only 2 cases
(4%), both of which contained wild-type TP53. Comparison with published results
from other geographic areas of high SCCE incidence revealed that the spectrum of
TP53 mutations in south Thailand is similar to that observed in central China
(Henan Province) but clearly differs from that of SCCE from western Europe
(Normandy, France; northern Italy), with more G:T transversions and fewer
mutations affecting A and T base pairs. These results suggest that SCCE from
south Thailand and from central China may involve similar risk factors.
PMID- 11004673
TI - Allelic loss in human intrahepatic cholangiocarcinoma: correlation between
chromosome 8p22 and tumor progression.
AB - Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary
tumor of the liver in Japan. Despite progress in operative techniques and
adjuvant therapy, the prognosis of ICC remains very poor. Therefore, it is
important to investigate the mechanism of carcinogenesis and progression of ICC.
We screened allelic losses at 6 loci, including that of novel tumor-suppressor
gene FEZ1 on chromosome 8p, and at 5 microsatellite loci to define the
association with tumor-suppressor genes (HNPCC, APC, RB1, p53, DCC) in tumors
from 18 unrelated ICC patients by PCR-loss of heterozygosity (LOH) assay and
correlated the alterations with clinicopathological parameters. As a result,
61.1% (11 of 18) of patients showed LOH at 1 of the loci at least, and
microsatellite instability was observed in 16.7% (3 of 18). At locus D8S258,
relatively frequent LOH was detected (17.6%) compared with other loci on
chromosome 8p. Among the other 5 chromosomal arms tested, the highest frequency
of LOH (23.5%) was observed at D17S153. Fifty percent of cases with the mass
forming + periductal infiltrating type were frequently detected by LOH at D8S258
compared to cases of the mass-forming or intraductal growth type. In conclusion,
we show that 1 putative tumor-suppressor gene on 8p22 may relate to progression
of ICC and suggest that the p53 tumor-suppressor gene may be associated with
carcinogenesis of ICC.
PMID- 11004674
TI - Immunization of cancer patients with autologous cancer-derived heat shock protein
gp96 preparations: a pilot study.
AB - Heat shock protein (HSP)-peptide complexes isolated from murine cancers elicit
protective immunity and T lymphocytes specific for the cancer from which the HSPs
are isolated. A pilot study was designed to test the feasibility, immunogenicity
and toxicity of such treatment in cancer patients. Sixteen patients with assorted
advanced malignancies, which had become refractory to established therapies, were
recruited. The gp96 vaccine was prepared for each patient from tumor obtained
from that patient. Anti-tumor immune responses were evaluated using Elispot
assays of T cells in peripheral blood after minimal in vitro stimulation. No
unacceptable vaccine-related toxicities or auto-immune reactions were observed.
Immunization with autologous gp96 elicited MHC I-restricted, tumor-specific
CD8(+) T lymphocytes in 6/12 patients immunized. In addition, expansion of the NK
cell population was seen in 8/13 of patients immunized. These observations are
entirely consistent with the murine experience and form a firm basis for future
trials with clinical end points, using autologous, patient-specific HSP-peptide
vaccines.
PMID- 11004675
TI - Defective antigen presentation resulting from impaired expression of
costimulatory molecules in breast cancer.
AB - Previous experiments from our laboratory have shown that immune mechanisms aiming
at the destruction of tumour cells including the recognition of target cells and
their elimination via the expression of intercellular adhesion molecule-1 (ICAM
1; CD54), the production of tumour necrosis factor-alpha (TNF-alpha) by monocytes
and appropriate function of lymphocyte subpopulations were defective in breast
cancer. Previous observations were extended to assess expression levels and
regulatory mechanisms of costimulatory molecules CD54, CD80 and CD86 on monocytes
derived from patients with early breast cancer (EBC). In addition, antigen
presentation by antigen-presenting cells (APC) was analyzed within this context.
We report that monocytes derived from patients with EBC exhibited significantly
decreased expression levels of CD54 (p = 0.0002), CD80 (p = 0.009) and CD 86 (p =
0.002) compared with monocytes derived from healthy females. Simultaneously,
lipopolysaccharide (LPS)-induced TNF-alpha production of monocytes was found to
be defective in patients with EBC. Finally, T-cell proliferation in response to
tetanus toxoid (TT) was significantly decreased in patients with EBC compared
with healthy control females (p < 0.0001). Furthermore, T-cell proliferation in
response to TT-pulsed APC derived from healthy controls was significantly
inhibited in the presence of anti-CD54 and/or anti-CD80 antibodies in a dose
dependent manner, thus corroborating the necessity of the presence of CD54 and
CD80 as costimulatory molecules in the present setting. We conclude that
monocytes derived from patients with EBC showed a simultaneous defect of
expression of CD54 and its regulation via TNF-alpha, CD80 and CD86 as well as T
cell proliferation following exposure to TT-pulsed APC. Based upon these
findings, it is speculated that defects in costimulatory molecule expression
might contribute to tolerance of the immune system towards the presence of
malignant cells in patients with EBC.
PMID- 11004676
TI - Tributyrin induces differentiation, growth arrest and apoptosis in androgen
sensitive and androgen-resistant human prostate cancer cell lines.
AB - Progression to androgen independence remains the main problem that impacts on
survival and quality of life in prostate cancer patients. We have investigated
the potency of tributyrin, an orally available prodrug of butyrate, to induce
growth arrest, differentiation and apoptosis in LNCaP, PC-3 and TSU-PR1 human
prostate cancer cell lines. Cells were treated with 0.1 to 5 mM tributyrin or
sodium butyrate. Growth inhibition, cell cycle arrest and apoptosis induction was
assessed using standard methods. Both agents induced a more differentiated,
fibroblast-like phenotype in androgen-sensitive as well as androgen-resistant
cell lines. Expression of prostate-specific antigen was increased in LNCaP cells
by tributyrin as a indicator of differentiation. The IC(50) for sodium butyrate
was 2.5 mM in PC-3 and TSU-PR1 cells. LNCaP cells exhibited <50% growth
inhibition at 5 mM sodium butyrate. However, the IC(50) for tributyrin was 0.8 mM
in PC-3 cells, 1.2 mM in TSU-PR1 cells and 3.1 mM in LNCaP cells. Flow cytometry
revealed a strong G1-arrest after exposure to tributyrin or sodium butyrate. Both
agents resulted in a strong increase of apoptosis rates compared with mock
treated cells. Overall, tributyrin had a 2.5- to 3-fold growth inhibitory and
apoptosis-inducing potency compared with equimolar concentrations of sodium
butyrate. Our results demonstrate that tributyrin is more potent than butyrate in
regard to cell growth inhibition and apoptosis induction at pharmacologically
relevant concentrations. Hence, tributyrin may be a promising candidate for
clinical protocols in prostate cancer.
PMID- 11004677
TI - Apoptotic responsiveness of the Ewing's sarcoma family of tumours to tumour
necrosis factor-related apoptosis-inducing ligand (TRAIL).
AB - We investigated the cytotoxic responsiveness of 40 cell lines derived from
representatives of the Ewing's sarcoma family of tumours (ESFT), i.e., Ewing's
sarcoma (ES), peripheral primitive neuroectodermal tumour (pPNET) and Askin
tumour (AT), to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL).
Incubation with TRAIL at 100 ng/ml induced cell death at 24 hr in 19 of 26 ES, 11
of 12 pPNET and 2 of 2 AT cell lines. Half-maximal cell death concentrations
(IC(50) values) varied from 0.1 to 20 ng/ml. TRAIL displayed potent cytotoxic
activity against freshly derived ESFT cell isolates. Cytotoxicity was associated
with phosphatidylserine expression and internucleosomal DNA fragmentation,
features characteristic of apoptosis. The apoptotic programme in the sensitive
ESFT VH-64 cell line revealed TRAIL-induced activation of FLICE/MACH1 (caspase-8)
and CPP32/Yama/apopain (caspase-3) and processing of the prototype caspase
substrate poly(ADP-ribose) polymerase. In addition, TRAIL provoked a collapse of
the mitochondrial transmembrane potential (DeltaPsi(m)), parallelled by a
reduction in ATP levels and release of cytochrome c from mitochondria into the
cytosol. Inhibition of caspase-8 and caspase-3 by zIETDfmk and zDEVDfmk,
respectively, substantially prevented TRAIL-induced apoptosis. However, zIETDfmk,
but not zDEVDfmk, reduced TRAIL-mediated DeltaPsi(m) dissipation, indicating that
TRAIL causes mitochondrial dysfunction through caspase-8 acting upstream of
mitochondria. While macromolecule synthesis inhibitors (actinomycin D,
cycloheximide) augmented susceptibility to TRAIL in TRAIL-responsive cell lines,
these agents did not render TRAIL-resistant cell lines susceptible to TRAIL.
However, the proteasome inhibitor MG132 sensitised to TRAIL in resistant cell
lines. Collectively, these results show that TRAIL initiates effective death in
the vast majority (80%) of cell lines derived from ESFT. Since TRAIL provoked
cell death in ESFT ex vivo, this cytokine may be a promising drug for the
treatment of ESFT in vivo.
PMID- 11004678
TI - New highly lipophilic camptothecin BNP1350 is an effective drug in experimental
human cancer.
AB - BNP1350, 7-[(2-trimethylsilyl)ethyl]-20(S)-camptothecin, is a novel semi
synthetic, highly lipophilic, silicon-containing camptothecin and an inhibitor of
topoisomerase I. It has been supercomputer engineered for superior oral
bioavailability, superior lactone stability, broad anti-tumor activity, increased
potency and insensitivity to Pgp/MRP/LRP drug resistance. We determined the
efficacy of BNP1350 in experimental human colon cancer and compared its anti
tumor effects with those of CPT-11/SN-38. We also determined a possible influence
of Pgp, MRP and LRP on the efficacy of BNP1350. The in vitro anti-proliferative
capacity of the compounds using various exposure times was assessed in five colon
cancer cell lines and indicated that BNP1350 was similarly effective or slightly
more potent than SN-38. Four cell lines of other origin with sublines expressing
Pgp, MRP and/or LRP showed that BNP1350 was significantly more effective than SN
38 (p < 0.05) and that the activity of BNP1350 was not reduced in multidrug
resistant cells. For in vivo experiments, BNP1350 was given 1.0 mg/kg i.p. or 1.5
mg/kg p.o. daily x 5 and CPT-11 20 mg/kg i.p. daily x 5 being equitoxic schedules
in nude mice bearing s.c. human tumor xenografts. The schedules were studied in
colon cancer xenografts COLO320, COLO205 or WiDr as well as in two Pgp-positive
xenografts 2780AD and BRO/mdr1.1 and the parental Pgp-negative A2780 ovarian
cancer xenografts and BRO melanoma xenografts. Growth inhibition of >50% was
obtained for BNP1350 given i.p. in six out of the seven xenografts studied.
BNP1350 was similarly effective when given i.p. or p.o. CPT-11 was as effective
as BNP1350, except in BRO and BRO/mdr1.1 xenografts. Pgp expression in xenografts
in vivo confirmed that there was no negative influence on the efficacy of
BNP1350. In conclusion, BNP1350 shows a broad spectrum of activity in
experimental human tumors and is a suitable candidate for oral treatment of
cancer.
PMID- 11004679
TI - A novel recombinant fusion toxin targeting HER-2/NEU-over-expressing cells and
containing human tumor necrosis factor.
AB - Over-expression of the proto-oncogene HER2/neu in breast cancer and certain other
tumors appears to be a central mechanism that may be partly responsible for
cellular progression of the neoplastic phenotype. Transfection of mammalian cells
and over-expression of HER2/neu appears to result in reduced sensitivity to the
cytotoxic effects of tumor necrosis factor (TNF) and reduced sensitivity to
immune effector killing. The single-chain recombinant antibody sFv23 recognizes
the cell-surface domain of HER2/neu. The cDNA for this antibody was fused to the
cDNA encoding human TNF, and this sFv23/TNF fusion construct was cloned into a
plasmid for expression in Escherichia coli. The fusion protein was expressed and
purified by ion-exchange chromatography. SDS-PAGE demonstrated a single band at
the expected m.w. (43 kDa). Western analysis confirmed the presence of both the
antibody component and the TNF component in the final fusion product. The fusion
construct was tested for TNF activity against L-929 cells and found to have
biological activity similar to that of authentic TNF (SA 420 nM). The scFv23/TNF
construct bound to SKBR-3 (HER2-positive) but not to A-375 human melanoma (HER2
negative) cells. Cytotoxicity studies against log-phase human breast carcinoma
cells (SKBR-3-HP) over-expressing HER2/neu demonstrate that the sFv23/TNF fusion
construct was 1, 000-fold more active than free TNF. Tumor cells expressing
higher levels of HER2/neu (SKBR-3-LP) were relatively resistant to both the
fusion construct and native TNF. These studies suggest that fusion constructs
targeting the HER2/neu surface domain and containing TNF are more effective
cytotoxic agents in vitro than native TNF and may be effective against tumor
cells expressing intermediate, but not high, levels of HER2/neu.
PMID- 11004680
TI - Cancer cell-targeted drug delivery utilizing oligopeptide transport activity.
AB - To study the drug delivery to tumor by utilization of an oligopeptide transport
activity, we examined the accumulation of dipeptides and the peptide-mimetic anti
cancer drug, bestatin, a substrate of oligopeptide transporter PepT1. Firstly, we
established HeLa cells stably expressing human peptide transporter (hPepT1) (HeLa
hPepT1). Secondly, we constructed an experimental model by inoculation of HeLa
hPepT1 cells subcutaneously into Balb/c nu/nu mice to demonstrate the
contribution of PepT1 to the tissue-selective drug delivery. The accumulations of
a hydrolysis-resistant dipeptide [(3)H]carnosine and bestatin in solid tumors
formed by HeLa-hPepT1 or HeLa-pcDNA3, which are transfected with vector DNA
(pcDNA3) were measured. After I.V. administration, tissue-to-plasma concentration
ratios (K(p)) of both compounds, in HeLa-hPepT1 tumor was significantly greater
than that of [(14)C]inulin, a marker for extracellular fluid space, those of
dipeptides in muscle, or those in HeLa-pcDNA3 tumor. Furthermore, bestatin
exhibited growth inhibition of HeLa-hPepT1 in vitro. In vivo, repeated oral
administration of bestatin for 28 days suppressed the growth of HeLa-hPepT1 tumor
specifically. When HT-1080 cells, which may naturally express oligopeptide
transport activity, were transplanted, K(p) of [(3)H]carnosine was significantly
increased in comparison with that in muscle. In addition, oligopeptide transport
activities among various human cell lines were examined. These results provide
the first demonstration for the selective delivery of oligopeptides to tumors by
specific oligopeptide transport activity.
PMID- 11004681
TI - Expression of SIALYL-Le(x) antigen defined by MAb AM-3 is an independent
prognostic marker in colorectal carcinoma patients.
AB - Expression of mucin-bound sialyl-Le(x) antigen during the progression of
colorectal carcinoma and its potential prognostic value were analysed in sections
of tumours from 182 patients with a documented follow-up by immunohistochemistry
using the monoclonal antibody (MAb) AM-3. Two groups of colonic carcinomas with
weak (n = 79) and strong (n = 103) sialyl-Le(x) expression were discerned. The
percentage of strongly expressing tumours increased with the progression of the
disease (UICC stage I = 10%, stage II = 46%, stage III = 63%, stage IV = 68%, p <
0.0001). Seventy-four percent of patients with carcinomas exhibiting a strong
sialyl-Le(x) expression but only 34% of patients with weak sialyl-Le(x)
expression died of the disease (p = 0.0026). In multivariate analysis, strong
sialyl-Le(x) expression increased the relative risk of cancer-related death 3.8
fold (95% CI = 1.8-7.9, p = 0.00034). The separate analyses of patients in UICC
stage II (n = 56), III (n =5 9) and IV (n = 57) revealed that strong sialyl-Le(x)
expression was associated with a reduction of the 5-year overall survival rate in
UICC stage II (84% vs. 54%, p = 0.0013) and in stage III patients (86% vs. 35%, p
= 0.0008) after curative resection but was not relevant in patients with distant
metastases. In conclusion, the strong expression of sialyl-Le(x) antigen defined
by the MAb AM-3 in colorectal carcinomas is an independent unfavourable
prognostic factor after curative resection in stage II and III patients. The
predictive power of the sialyl-Le(x) expression may be helpful to define
subgroups of patients at high risk for whom preventive adjuvant therapy can be
selectively applied before the occurrence of detectable metastases.
PMID- 11004682
TI - Overcoming cisplatin resistance in vitro by a free and liposome-encapsulated bile
acid derivative: BAMET-R2.
AB - Low water solubility and development of resistance are important drawbacks in the
use of cisplatin as a cytostatic agent. A novel bile acid-cisplatin complex,
Bamet-R2 [cis-diamminechlorocholylglycinateplatinum (II)], with liver
vectoriality, has been synthesized. Our aim was to investigate the usefulness of
this compound to overcome cisplatin resistance and to determine whether its
encapsulation into liposomes increases its water solubility, uptake by liver
tumor cells and cytostatic activity. Highly efficient incorporation of Bamet-R2
into liposomes permitted an increase in the concentration of the drug compared
with that in the initial free solution by more than 6 x 10(6)-fold, which is
10(3)-fold higher than the encapsulation obtained for cisplatin. A partially
cisplatin-resistant (87-fold) monoclonal cell line (Hepa 1-6/10R) was obtained by
2 subcloning steps of a population of mouse hepatoma Hepa 1-6 cells grown in step
wise increasing cisplatin concentrations up to 10 microM. Decreased sensitivity
to cisplatin was accompanied by a 3.2-fold lower drug accumulation compared to
wild-type cells. Uptake was markedly increased by the binding of cisplatin to
glycocholic acid in both Hepa 1-6 and Hepa 1-6/10R cells. This probably accounts
for the partial overcoming (-82%) of resistance when used on Hepa 1-6/10R cells.
Inclusion of Bamet-R2 into liposomes further increased the amount of the drug
accumulated in both cell types and, hence, enhanced its cytostatic activity.
Since both plain liposomes and Bamet-R2 have little toxicity, the formulation of
this compound in liposomes may offer a substantial advantage over cisplatin in
the treatment of tumors resistant to this anti-neoplastic agent.
PMID- 11004683
TI - Expression of the major vault protein LRP in human non-small-cell lung cancer
cells: activation by short-term exposure to antineoplastic drugs.
AB - Non-small-cell lung cancer (NSCLC) cells are characterised by resistance to the
toxic impact of antineoplastic drugs both in vivo and in vitro. The lung
resistance-related protein (LRP), identical with the human major vault protein,
is over-expressed in a variety of tumour cells characterised by intrinsic or
acquired chemoresistance. We investigated the expression and cellular
localisation of LRP in 16 unselected NSCLC cell lines, immortalised bronchial
epithelial cells and embryonic lung fibroblasts. All cell lines analysed
expressed LRP mRNA, while protein expression ranged from undetectable up to high
levels. Cell fractionation and immunofluorescence staining in selected cell lines
localised LRP almost exclusively to the cytoplasm. LRP was contained in the 100,
000 g pellet and absent in the soluble, cytosolic fraction and nuclei. A small
proportion of LRP, however, was shown to be loosely associated with the outside
of the nuclei. Sucrose gradient equilibrium centrifugation revealed presence of
LRP exclusively in the fraction known to accumulate purified vault particles.
Short-term exposure (16 hr) to subtoxic daunomycin (DM)-, and bleomycin (BM)
concentrations significantly (up to 4-fold) enhanced LRP expression in 2/4 cell
lines tested. Cisplatin (CDDP) had a minor effect while vinblastine (VBL) was
ineffective. At cytotoxic conditions all drugs rather decreased than increased
LRP expression. When basic LRP expression was compared with chemosensitivity, a
significant correlation was detected for resistance to CDDP but not DM,
doxorubicin (DOX), etoposide (VP-16), VBL and BM. Summing up, our data suggest a
role of vaults both in basic CDDP resistance and, additionally, in an short-term
defensive response of NSCLC cells against several other drugs.
PMID- 11004684
TI - Cancer occurrence after cosmetic breast implantation in Denmark.
AB - Most studies on cancer incidence after breast implantation have focused on breast
cancer, while the risk of cancers at other sites has been less well investigated.
We examined cancer incidence among 1,653 women who underwent cosmetic breast
implant surgery at private clinics of plastic surgery in Denmark and 1,736 women
attending the same clinics for other reasons during the period 1973-1995.
Furthermore, we updated previously reported results among 1,114 women who
received implants for cosmetic indications at public hospitals. All women were
followed for cancer through the Danish Cancer Registry. In comparison with the
general female population, the overall standardized incidence ratio (SIR) for
cancer among women who received implants in private clinics was 1.65 [95%
confidence interval (CI) = 1.17-2.27]. This elevated SIR reflected increased
incidence ratios for almost all major cancer sites; however, only for non
melanoma skin cancer was there an excess of more than 2 cases. No significant
excess of cancer was observed among women who received implants in public
hospitals (SIR = 1.10, 95% CI = 0.76-1.52) or among women attending the private
clinics for other problems (SIR = 1.10, 95% CI = 0.78-1.52). The SIRs for breast
cancer after breast implantation were 1.1 (95% CI = 0.5-2.2) among private clinic
patients and 0.9 (95% CI = 0.4-1.7) among public hospital patients. The overall
findings of these 2 implant cohorts and results from other investigations suggest
that cancer risk is probably not increased among women receiving cosmetic breast
implants. The inconsistent results for private clinics and public hospitals are
likely related to selection bias and confounding among the private clinic
patients, but our data did not permit exploration of these possibilities. Further
research into the determinants of these inconsistencies is warranted.
PMID- 11004685
TI - Nationwide cancer family ascertainment using Finnish Cancer Registry data on
family names and places of birth for 35,761 prostate cancer patients.
AB - Identification of predisposition loci to complex diseases, such as prostate
cancer, requires high-quality family material, the ascertainment of which is
often laborious, time-consuming and inaccurate with conventional methods. Here,
we describe a new method for rapid, nationwide cancer family ascertainment using
Finnish Cancer Registry data on 35,761 prostate cancer cases over a 40-year
period. As members of a prostate cancer family are likely to share the same
family name and place of birth, we stratified all prostate cancer cases by these
2 parameters (10,721 different names and 596 municipalities). Data were compared
with the distribution of family names and places of birth for all 3.3 million
Finnish men to derive standardized prevalence ratios (SPRs). A significantly
elevated SPR of prostate cancer was detected for 468 (1.6%) of the 28,459
evaluable combinations of family name and place of birth. Of the 20 highest SPR
values, 19 corresponded to true nuclear families, most of these having 3 or more
affected cases. Two-thirds of our 50 previously established Finnish prostate
cancer families were classified among this 1.6% fraction of the highest SPR
values. Finally, many of the highest SPR values originated from municipalities in
southern and south-western Finland. To explore whether such clusters could
highlight local founder effects, we applied genealogical research to link
together several families with elevated SPRs and identified an extended family
with 20 prostate cancer cases with common ancestors in the early seventeenth
century. In summary, a rapid novel method was developed and validated for
identification of prostate cancer families from nationwide cancer registry data
and for the identification of putative regional founder effects.
PMID- 11004686
TI - Population based study of coffee, alcohol and tobacco use and risk of ovarian
cancer.
AB - Coffee, alcohol and tobacco use have been examined in many epidemiologic studies
of ovarian cancer but findings have generally been inconclusive. To explain prior
inconsistent findings, we sought to determine whether associations with these
exposures might vary by histologic subtype of ovarian cancer or menopausal status
at diagnosis. We conducted a population-based case-control study in eastern
Massachusetts and New Hampshire involving 549 women with newly-diagnosed
epithelial ovarian cancer and 516 control women selected either by random digit
dialing or through lists of residents. Coffee and alcohol consumption was
assessed through a semi-quantitative food-frequency questionnaire, and
information on tobacco smoking was collected through personal interview.
Consumption of coffee and caffeine was associated with increased risk for ovarian
cancer but only among premenopausal women. There was no increase in risk for
ovarian cancer overall associated with tobacco or alcohol use in either pre- or
post-menopausal women. Association of borderline significance for tobacco and
invasive serous cancers and alcohol and mucinous cancers were observed but
reduced after adjustment for coffee consumption. We conclude that coffee and
caffeine consumption may increase risk for ovarian cancer among premenopausal
women and are findings that have some epidemiologic and biologic support.
PMID- 11004687
TI - Loss of heterozygosity (LOH) at p53 is correlated with LOH at BRCA1 and BRCA2 in
various human malignant tumors.
PMID- 11004688
TI - Malignant hypertension - the role of the paracrine renin-angiotensin system.
AB - Malignant hypertension remains one of the life-threatening complications of blood
pressure elevation. It is a clinico-pathological syndrome of severe blood
pressure elevation combined with malignant vascular injury. This is a
characteristic form of vascular damage, with two elements: fibrinoid necrosis and
endarteritis proliferans. Although the morphology of these has been well
described, the molecular events are not fully understood. This review summarizes
the evidence from transgenic animals for a role for the activation of a local
paracrine renin-angiotensin system in the pathogenesis of malignant vascular
injury. These animal models provide pathological, pharmacological, and genetic
evidence supporting the hypothesis that intra-renal generation of angiotensin 2
and exposure of the microcirculation to elevated blood pressure co-operate in
causing tissue damage in malignant hypertension.
PMID- 11004689
TI - 'Invading edge vs. inner' (edvin) patterns of vascularization: an interplay
between angiogenic and vascular survival factors defines the clinical behaviour
of non-small cell lung cancer.
AB - Neo-angiogenesis during neoplastic growth involves endothelial mitogenic and
migration stimuli produced by cancer or tumour stromal cells. Although this
active angiogenesis takes place in the tumour periphery, the process of vessel
growth and survival in inner areas and its clinical role remain largely
unexplored. The present study compared the microvessel score (MS) as well as the
single endothelial cell score (ECS) in the invading edge and in inner areas of
non-small cell lung carcinomas (NSCLCs). Three different patterns of vascular
growth were distinguished: the edvin (edge vs. inner) type 1, where a low MS was
observed in both peripheral and inner tumour areas; the edvin type 2, where a
high MS was noted in the invading front but a low MS in inner areas; and the
edvin type 3, where both peripheral and inner tumour areas had a high MS. The ECS
was high in the invading edge in edvin type 2 and 3 cases and was sharply
decreased in both types in inner areas, suggesting that endothelial cell
migration is unlikely to contribute to the angiogenic process in areas away from
the tumour front. Expression of the vascular endothelial growth factor (VEGF) and
of thymidine phosphorylase (TP) was associated with a high MS in the invading
edge. VEGF was associated with a high MS in inner areas (edvin 3), while TP
expression was associated with edvin type 2, showing that VEGF (and not TP)
contributes to the preservation of the inner vasculature. Both edvin type 2 and 3
cases showed an increased incidence of node metastasis, but edvin type 3 cases
had a poorer prognosis, even in the N1-stage group. The present study suggests
that tumour factors regulating angiogenesis and vascular survival are not
identical. A possible method is reported to quantify these two parameters by
comparing the MS in the invading edge and inner areas (edvin types). This
observation may contribute to the evaluation of the effectiveness of different
therapeutic approaches, namely vascular targeting vs. anti-angiogenesis.
PMID- 11004690
TI - Expression of vascular endothelial growth factor by macrophages is up-regulated
in poorly vascularized areas of breast carcinomas.
AB - Angiogenesis is essential to the growth and metastasis of solid tumours. Vascular
endothelial growth factor (VEGF) is a potent pro-angiogenic cytokine that is
overexpressed in malignant tumours such as invasive carcinoma of the breast. The
low oxygen tensions (hypoxia) present in these tumours are known to up-regulate
the expression of VEGF by tumour cells. Human macrophages also respond to hypoxia
by increasing their release of VEGF in vitro, although the effect of hypoxia on
VEGF expression by macrophages in vivo has yet to be demonstrated. The present
study compared the expression of VEGF by macrophages in areas of low and high
vascularity in 24 invasive breast carcinomas (12 lobular, 12 ductal). The
cellular distributions of VEGF protein, CD31 (vessels), and CD68 (macrophages)
were compared in sequential sections for each tumour. In ten tumours, both tumour
cells and macrophages were immunoreactive for VEGF protein. Use of non-isotopic
in situ hybridization to localize VEGF mRNA showed that these cell types also
expressed VEGF mRNA. No significant differences in the cellular distribution of
VEGF protein were found between lobular and ductal carcinomas. In all tumours,
macrophages accumulated in higher numbers in poorly vascularized than in highly
vascularized areas. In VEGF-positive tumours, macrophages were immunoreactive for
VEGF only in avascular areas where tumour cells also expressed VEGF. This
suggests that VEGF expression by these two cell types may be regulated by the
same microenvironmental stimuli in breast carcinomas. In addition, significantly
more macrophages were present in poorly vascularized areas of VEGF-positive than
VEGF-negative tumours. This suggests that VEGF may exert a chemotactic action on
macrophages in vivo and guide their migration into avascular tumour sites.
PMID- 11004691
TI - Expression of oestrogen receptor alpha variants in non-malignant breast and early
invasive breast carcinomas.
AB - Oestrogen receptor (ER) alpha variants have been described in normal breast and
breast carcinomas, but their presence in a range of benign conditions and in
small early invasive breast carcinomas has not been considered. Cryostat tissue
sections from 19 normal and proliferative breast lesions and 44 carcinomas 15 mm
and less in size detected by mammographic screening were screened for ERalpha
splice variants using reverse transcriptase-nested PCR. The carcinomas were
assessed for mutation by single-stranded conformational polymorphism analysis and
variant forms/band shifts were sequenced. ERalpha was detected in all 19 non
malignant cases and exon 7-deleted variants were found in 16 of them. Three cases
showed weak expression of exon 5, and two of exon 3 variants. There was no
relationship between the presence of variants and the extent of proliferative
change, ER status or age. ERalpha mRNA was not detected in two carcinomas; exon 3
deletions were found in four (9. 5%) of the other carcinomas, exon 5 in two
(4.8%), and exon 7 in 11 (26.2%), with two variants in four carcinomas and a
total of 29.5% of all cases having detectable variants. Two point mutations were
found in one, which was a tubular carcinoma. Variant forms were identified in
carcinomas of all sizes (bar<10 mm) but were more frequent in those of 15 mm.
There was no relationship with type, grade or receptor status. The main
difference between non-malignant breast and early invasive cancers related to
exons 3 and 5. The findings suggest that ERalpha variants are not involved in
breast cancer development but occur with tumour progression and may be a
consequence rather than a cause.
PMID- 11004692
TI - Apoptosis, proliferation, and Fas (APO-1, CD95)/Fas ligand expression in
medullary carcinoma of the breast.
AB - Medullary carcinoma (MC) of the breast is a unique subtype of infiltrating ductal
carcinoma that is characterized by a prominent lymphoid infiltrate and improved
prognosis. Activated granzyme B(+)/CD8(+) cytotoxic T-lymphocytes (CTLs)
infiltrating tumour cell nests constitute a major subset within the lymphoid
infiltrate. As CTLs destroy target tumour cells by triggering apoptosis, it would
be of interest to determine whether the apoptotic rate in MC is increased. This
study evaluates the extent of apoptosis in relation to Fas (APO-1, CD95)/Fas
ligand (FasL) expression in MC. Fourteen cases of typical MC (TMC) and 15 cases
of atypical MC (AMC) classified according to the Ridolfi criteria, as well as 19
cases of poorly differentiated infiltrating ductal carcinoma (PDC) were
evaluated. The apoptotic index (AI) was assessed by the TUNEL method on paraffin
embedded tissue. Cell proliferation was evaluated immunohistochemically by PCNA
staining. The level of Fas/FasL expression was determined semiquantitatively by
immunohistochemistry using a four-grade scoring system. The AI was significantly
increased in TMC and AMC as opposed to the PDC subgroup (2.2+/-0.8, 2.1+/-0.8,
and 1.3+/-0.6, respectively; p<0.05). A significant proportion (31.8+/-7.9% in
TMC and 25.8+/-9.7% in AMC) of the apoptotic tumour cells within tumour nests
were in close contact with CD3(+) lymphocytes. Increased apoptosis was not
accompanied by increased proliferation of tumour cells. The extent of Fas
expression did not differ between the three subgroups. FasL was expressed both by
tumour infiltrating lymphocytes in MC and by tumour epithelium in all three
subgroups. The observation that the majority of MCs express Fas and are
infiltrated by lymphocytes expressing FasL suggests that increased apoptosis in
MC is mediated by Fas/FasL. However, our observation that the majority of MCs
also express FasL and the fact that tumours co-expressing Fas and FasL did not
show increased apoptosis suggest that there may be additional cytotoxic pathways
that lead to tumour apoptosis in MC.
PMID- 11004693
TI - Relationship between expression of topoisomerase II isoforms and chemosensitivity
in choroidal melanoma.
AB - Choroidal melanoma has a high mortality rate and responds poorly to existing
chemotherapy, but unexpected ex vivo sensitivity of a subset of these tumours to
topoisomerase II inhibitors has been noted. Since chemoresistance may be mediated
by the molecular phenotype of tumours, immunohistochemistry has been used to
study the expression of both isoforms of topoisomerase II (alpha and beta) in 29
choroidal melanomas for which chemosensitivity assay data for doxorubicin or
mitoxantrone are also available. Of these, eight tumours were topoisomerase II
beta-positive and 11 were topoisomerase II alpha-positive. Recent studies showing
genetic abnormality (often monosomy of chromosome 3) in choroidal melanoma
suggest that loss of immunostaining could be due to genomic loss rather than down
regulation of topoisomerase II beta in these tumours. There was no convincing
excess of anthracycline resistance in the topoisomerase II beta-negative group.
Addition of topoisomerase II alpha, MDR1 (11/17 positive), LRP (16/28 positive),
and MRP (5/29 positive) data in multivariate analysis did not reliably predict
sensitivity or resistance. Vincristine chemosensitivity showed no relation to
MDR1, LRP or MRP in 18 tumours tested. While it is possible that some tumours
which do express topoisomerase II beta may respond to anthracyclines, the
molecular basis of resistance or sensitivity to anthracyclines or vincristine in
uveal melanoma is complex and remains incompletely understood.
PMID- 11004694
TI - The restricted expression pattern of the Hodgkin's lymphoma-associated cytokine
receptor CD30 is regulated by a minimal promoter.
AB - One of the most peculiar immunohistological characteristics of the tumour cells
of Hodgkin's lymphoma, anaplastic large cell lymphoma (ALCL), and embryonal
carcinoma of the testis is the expression of the CD30 antigen. Physiologically,
CD30 expression is restricted to a few activated lymphocytes in normal lymphoid
tissue and a small population of decidual cells. To clarify the reasons behind
this highly restricted expression pattern and to learn about the combination of
transcription factors involved in this regulation in Hodgkin's lymphoma and other
CD30(+) malignancies, the 5'-flanking regulatory region of the cd30 gene was
analysed. The major transcription start site was determined to be 270 bases
upstream of the translational start codon in the Hodgkin's lymphoma-derived cell
lines L591 and L428. Reporter gene assays revealed that the CD30 promoter (-413
to 84) induces a 50- to 1000-fold higher luciferase expression in CD30(+) human
lymphoid cell lines (Co, Jurkat, and the Hodgkin's lymphoma-derived cell line
L540) than in CD30(-) human lymphoid cell lines (DG75, SUP-T1, and U698M), CD30(
) human carcinoma cell lines (HeLa and MCF-7), or COS1 cells. Deletion analysis
defined a TATA-less, minimal promoter sequence from -164 to 84. The transcription
factor Sp1 and members of the Ets family induce CD30 expression, whereas the
transcription factor Sp3 diminishes its induction. These data suggest that a high
Sp1/Sp3 expression ratio and a peculiar expression pattern of the Ets
transcription factors are involved in the overexpression of CD30 and might
contribute to the transformation of CD30(+) tumour cells.
PMID- 11004695
TI - Frequent nuclear localization of ICAD and cytoplasmic co-expression of caspase-8
and caspase-3 in human lymphomas.
AB - Lymphoma cells often display in vitro resistance to FAS-induced apoptosis, in
which caspases act as crucial cell death effectors. Following FAS stimulation,
caspase-8 activates caspase-3, which in turn activates the caspase-activated
DNAse (CAD) by proteolysis of its inhibitor (ICAD). To investigate the mechanism
of FAS resistance, the expression of caspase-8 was analysed by
immunohistochemistry, together with that of the substrates caspase-3 and ICAD, in
52 representative samples from non Hodgkin's lymphoma (NHL), 12 from Hodgkin's
disease (HD), and eight benign lymphoid tissues. In benign tissues, caspase-8 was
co-expressed with caspase-3 in the cytoplasm in germinal centre (GC) cells and
was co-expressed with ICAD in the nuclei of the mantle and marginal zone cells.
ICAD expression was weak or absent in GC cells. Cytoplasmic staining for both
caspase-8 and caspase-3 was present in 11/12 cases of diffuse large cell B-NHL.
Caspase-8 positivity was nuclear and cytoplasmic in 9/9 follicular NHLs, in 5/5
mantle cell NHLs and in 6/6 marginal zone NHLs. Five out of six peripheral T-cell
NHLs expressed cytoplasmic caspase-8. Ten out of the 12 HD cases lacked
significant cytoplasmic staining for caspase-3 and caspase-8 in the majority of
Reed-Sternberg cells. All lymphoma cases exhibited predominant nuclear ICAD
positivity. Subcellular fractionation analysis of three lymphoma samples and
normal mantle zone cells confirmed that ICAD and caspase-8 were at least partly
localized in the nucleus. These results show that the profile of caspase-8
expression is correlated with histological lymphoma subtypes; that caspase-8 is
co-expressed with caspase-3 in GC cells and their neoplastic counterparts; that
ICAD has an immunohistochemical nuclear localization in vivo; and that caspase-8
and ICAD can be co-expressed in the nuclei of mantle zone and marginal zone
cells; their unexpected nuclear localization allows a reappraisal of the
biochemical cascade of caspase activation.
PMID- 11004696
TI - In situ analysis of LKB1/STK11 mRNA expression in human normal tissues and
tumours.
AB - The LKB1/STK11 serine/threonine kinase is mutated in Peutz-Jeghers' syndrome and
acts as a tumour suppressor. Using northern blotting and RT-PCR, LKB1 has been
reported to be expressed widely in human adult tissues, although in Xenopus the
expression of its homologue, XEEK1, is apparently restricted to early
embryogenesis. In situ hybridization has been used to detect and localize LKB1
mRNA in a variety of adult and fetal tissues and tumours. The results show that
LKB1 expression is widespread, but predominant in epithelia and in the
seminiferous tubules of the testis. Expression is higher in fetal than in adult
tissues. Expression also appears to be higher in many malignant tumours than in
normal tissues or benign lesions, although some cancers have lost LKB1
expression, quite possibly as part of the process of tumourigenesis. These data
are consistent with a widespread functional role for LKB1 in tissues of most
types, and with a role for LKB1 in the pathogenesis of some sporadic cancers.
LKB1 expression may primarily be related to the rate of cell replication.
PMID- 11004697
TI - Molecular cytogenetic evaluation of virus-associated and non-viral hepatocellular
carcinoma: analysis of 26 carcinomas and 12 concurrent dysplasias.
AB - The worldwide incidence of hepatocellular carcinoma (HCC) is approximately one
million cases a year. This makes HCC one of the most frequent human malignancies,
especially in Asia and Africa, although the incidence is increasing also in the
western world. HCC is a complication of chronic liver disease, with cirrhosis as
the most important risk factor. Viral co-pathogenesis makes cirrhosis due to
hepatitis B (HBV) and hepatitis C virus (HCV) infection a very important factor
in the development of HCC. As curative therapy is often ruled out due to the late
detection of HCC, it would be attractive to find parameters which predict
malignant transformation in HBV- and HCV-infected livers. This study has used
comparative genomic hybridization (CGH) to analyse 26 HCCs (11 non-viral, nine
HBV, six HCV) and 12 concurrent dysplasias (five non-viral, five HBV, two HCV).
Frequent gain (> or =25% of all tumours) was detected, in decreasing order of
frequency, on 8q (69%), 1q (46%), 17q (46%), 12q (42%), 20q (31%), 5p (27%), 6q
(27%), and Xq (27%). Frequent loss (> or =25% of all tumours) was found, in
decreasing order of frequency, on 8p (58%), 16q (54%), 4q (42%), 13q (39%), 1p
(35%), 4p (35%), 16p (35%), 18q (35%), 14q (31%), 17p (31%), 9p (27%), and 9q
(27%). Minimal overlapping regions could be determined at multiple locations
(candidate genes in parentheses). Minimal regions of overlap for deletions were
assigned to 4p14-15 (PCDH7), 8p21-22 (FEZ1), 9p12-13, 13q14-31 (RB1), 14q31
(TSHR), 16p12-13.1 (GSPT1), 16q21-23 (CDH1), 17p12-13 (TP53), and 18q21-22 (DPC4,
DCC). Minimal overlapping amplified sites could be seen at 8q24 (MYC), 12q15-21
(MDM2), 17q22-25 (SSTR2, GH1), and 20q12-13.2 (MYBL2, PTPN1). A single high level
amplification was seen on 5q21 in an HBV-related tumour. Aberrations appeared
more frequent in HBV-related HCCs than in HCV-associated tumours (p=0.008). This
was most prominent with respect to losses (p=0.004), specifically loss on 4p
(p=0.007), 16q (p=0.04), 17p (p=0.04), and 18q (p=0.03). In addition, loss on 17p
was significantly lower in non-viral cancers than in HBV-related HCC (p<0.001).
Furthermore, loss on 13q was more prevalent in HCCs in non-cirrhotic livers
(p=0.02), thus suggesting a different, potentially more aggressive, pathway in
neoplastic progression. A tendency (p=0.07) was observed for loss on 9q in high
stage tumours; no specific changes were found in relation to tumour grade. A
subset of the HCC-associated genetic changes was disclosed in the preneoplastic
stage, i.e. liver cell dysplasia. This group of dysplasias showed frequent gain
on 17q (25%) and frequent loss on 16q (33%), 4q (25%), and 17p (25%). The
majority of the dysplasias with alterations revealed genetic changes that were
also present in the primary tumour. In conclusion, firstly, this study has
provided a detailed map of genomic changes occurring in HCC of viral and non
viral origin, and has suggested candidate genes. Loss on 17p, including the TP53
region, appeared significantly more prevalent in HBV-associated liver cancers,
whereas loss on 13q, with possible involvement of RB1, was distinguished as a
possible genetic biomarker. Secondly, CGH analysis of liver cell dysplasia, both
viral and non-viral, has revealed HCC-specific early genetic changes, thereby
confirming its preneoplastic nature. Finally, genes residing in these early
altered regions, such as CDH1 or TP53, might be associated with hepatocellular
carcinogenesis.
PMID- 11004698
TI - p120 expression provides a reliable indication of the rapidity of cell
duplication in cancer cells independently of tumour origin.
AB - p120 is a nucleolar protein that has been immunocytochemically detected in
rapidly proliferating cells of a variety of human malignancies. In the present
study, the relationship between p120 expression and the rapidity of cell
proliferation was evaluated in 48 human tumours of different origins. The cell
proliferation rate of cancer cells was determined by quantitative analysis of
AgNOR proteins. p120 immunostaining and AgNOR protein quantity were measured by
image cytometry and a highly significant correlation was found between the two
variables, as evaluated by linear regression analysis (r=0.98, p<0.0001). The
relationship between p120 expression and the rapidity of cell duplication was
also studied in vitro, in six human cancer cell lines derived from different
tumour types, characterized by various doubling times (ranging from 20 to 77 h).
p120 expression was determined on western blots using specific anti-p120
monoclonal antibodies. Densitometric analysis revealed a highly significant
inverse correlation between the integrated optical density values of the
chemoluminescence bands at 120 kD and the cell line doubling times (r=-0.93;
p=0.007). The same result was obtained in situ by correlating p120 immunostaining
of the cytological preparations obtained from the six cancer cell lines with the
corresponding doubling time (r=-0.98, p<0.0001). These results indicate that in
cancer cells, the quantitative expression of p120 is directly related to the
rapidity of cell duplication, independently of the tumour origin.
PMID- 11004699
TI - Clonal patterns in phaeochromocytomas and MEN-2A adrenal medullary hyperplasias:
histological and kinetic correlates.
AB - The relationship among histological features, cell kinetics, and clonality has
not been studied in adrenal medullary hyperplasias (AMHs) and phaeochromocytomas
(PCCs). Thirty-four PCCs (23 sporadic and 11 MEN-2A (multiple endocrine neoplasia
type 2A)-related tumours, the latter associated with AMH) from females were
included in this study. Representative samples were histologically evaluated and
microdissected to extract DNA and evaluate the methylation pattern of the
androgen receptor alleles. At least two tissue samples (from the peripheral and
internal zones in each tumour) were analysed with appropriate tissue controls run
in every case. The same areas were selected for MIB-1 staining and in situ end
labelling (ISEL). Malignant PCCs were defined by histologically confirmed distant
metastases. All monoclonal AMH nodules from the same patient showed the same X
chromosome inactivated. Six sporadic PCCs revealed liver metastases (malignant
PCC) and eight additional sporadic PCCs showed periadrenal infiltration (locally
invasive PCC). All informative PCCs were monoclonal, except for five locally
invasive PCCs and one benign PCC that revealed polyclonal patterns. Those cases
also showed a fibroblastic stromal reaction with prominent blood vessels, focal
smooth muscle differentiation, and significantly higher MIB-1 (126.8+/-29.9) and
ISEL (50.9+/-12.8) indices. Concordant X-chromosome inactivation in nodules from
a given patient suggests that MEN-2A AMH is a multifocal monoclonal condition. A
subgroup of PCCs characterized by balanced methylation of androgen receptor
alleles, high cellular turnover, and stromal proliferation also shows locally
invasive features.
PMID- 11004700
TI - Errors in histological grading by prostatic needle biopsy specimens: frequency
and predisposing factors.
AB - Sampling error is an inherent problem of prostate biopsy. Consequently, there are
problems in determining whether a given carcinoma is clinically significant on
the basis of biopsy results. This study assesses the factors that predispose to
errors in biopsy grading, as well as the dimensions of sampling error due to
these factors. Among 187 cases, biopsy grading error was retrospectively related
to grade heterogeneity in the prostate and to biopsy-related factors. Clinically
relevant biopsy grading errors occurred in a quarter of the cases. Of all grading
errors, at least 17% resulted from misinterpretation by the pathologist only.
Overall, prostates with grade heterogeneity revealed grading errors twice as
frequently as specimens without grade heterogeneity. In most cases, however,
grading error resulted from multiple factors, such as the number and length of
cores obtained (p<0.05). This was an important finding because the mean core
length was only 9.4 mm, whereas the biopsy needle is designed to obtain cores of
15 mm. Moreover, clinically relevant biopsy grading error had occurred in almost
half of the cases when the Gleason score was based on a tumour deposit measvring
less than 0.5 mm (p<0.05). The clinical consequences of these findings are
important. Clinicians should try to obtain at least six biopsies, each 15 mm in
length, to minimize grading error. Pathologists should be cautious in reporting
Gleason scores based on tumour lesions smaller than 400x total magnification
field. Interpretation could be refined, when necessary, by warning the urologist
of the Limitations of the biopsy report.
PMID- 11004701
TI - Expression of angiogenic factor thymidine phosphorylase and angiogenesis in human
atherosclerosis.
AB - In atherosclerosis, leukocyte migration into the plaque is thought to occur
across the endothelium of the arterial lumen. However, intraplaque microvessels
have been noted. While the significance of, and stimuli for these are uncertain,
it seems possible that they may represent a second portal of entry for leukocytes
into the plaque. This study performed a basic characterization of intraplaque
microvessels and tested the hypothesis that the novel angiogenic factor thymidine
phosphorylase (TP) is expressed in atherosclerosis. Immunocytochemistry was
performed on aortic and coronary plaques and morphometry on coronary plaques. In
plaques from both sites, macrophages, foam cells, and giant cells were
immunoreactive for the angiogenic factors TP and vascular endothelial growth
factor. Venule-like intraplaque microvessels expressed endothelial leukocyte
adhesion molecules HLA-DR and ICAM-1, in contrast to the endothelium overlying
the plaque. In coronary plaques, there was a correlation between severity of
stenosis and plaque microvascular density. These results are consistent with a
role for plaque macrophage/foam cell TP in stimulating plaque angiogenesis. While
attention has focused on dysfunction of the endothelium overlying the plaque,
microvascular endothelium may also represent a portal of entry for leukocytes
into established plaques.
PMID- 11004702
TI - The relationship between persistent secretion of RANTES and residual infiltration
of eosinophils and memory T lymphocytes after Helicobacter pylori eradication.
AB - Helicobacter pylori (HP)-infected gastric mucosa displays a conspicuous
infiltration of mononuclear cells as well as neutrophils. RANTES is a potent
chemoattractant peptide for memory T lymphocytes and eosinophils. RANTES protein
concentration and the numbers of RANTES-, CD45RO-, and major basic protein (MBP)
positive cells were therefore evaluated in the gastric mucosa from 51 patients
with HP-positive chronic gastritis before and after HP eradication and from 22 HP
negative healthy volunteers. RANTES protein concentration was significantly
elevated in HP-positive cases and remained high after HP eradication. The numbers
of RANTES-, CD45RO-, and MBP-positive cells were significantly increased in HP
positive cases and were well correlated with RANTES protein levels. All tended to
decrease after HP eradication, but did not reach the level of HP-negative cases,
even at 24 months after HP eradication. It was concluded that persistent
expression and secretion of RANTES were closely related to residual infiltration
of memory T lymphocytes and eosinophils, for a prolonged period after HP
eradication. This seems to be an important mechanism of prolonged gastric mucosal
immune response against HP infection, even after HP eradication, and of
persistent mucosal damage and atrophy.
PMID- 11004703
TI - Increased expression of cytoplasmic tail-containing form of gp600/megalin in
active Heymann nephritis.
AB - Active Heymann nephritis of rat, an autoimmune glomerular disease, is a model of
human membranous glomerulonephropathy. The major target autoantigen of this
disease is a 600 kD renal glycoprotein, variously named gp600/gp330/megalin/LRP2.
It has been shown previously that there is a marked increase in the gp600/megalin
mRNA level in glomeruli of rats with this disease. A rabbit antibody was prepared
against a peptide located at the very end of the cytoplasmic tail of rat
gp600/megalin. Affinity purified anti-peptide antibody was monospecific and
reacted only with gp600/megalin on the immunoblots of total kidney proteins.
Immunofluorescence microscopy on frozen kidney sections probed with this antibody
revealed the presence of the cytoplasmic tail-containing form of gp600/megalin in
both proximal tubules and glomeruli. Expression in glomeruli of normal kidneys
was less than in tubules but was clearly detectable. In active Heymann nephritis
kidneys, expression of this form was increased most remarkably in glomeruli.
These results, showing increased expression of the cytoplasmic tail-containing
form in active Heymann nephritis glomeruli, contradict previous reports of its
absence. This is the first study to show that there is increased expression of
the cytoplasmic tail-containing form of gp600/megalin in the glomeruli of rats
with this disease and its role in active Heymann nephritis is discussed.
PMID- 11004704
TI - The effect of environmental cues on the differentiation of myofibroblasts in
peritoneal granulation tissue.
AB - This study investigated the effect of haemodynamic stress, active stretch, and
neuronal input on the differentiation of myofibroblasts in peritoneal granulation
tissue. Lengths of silastic tubing (10 mm long x 3 mm diameter) were placed in
the peritoneal cavity of the rat. By 2 weeks, a capsule of granulation tissue had
formed around the tubing. This capsule consisted of several layers of
myofibroblasts and the matrix that they had produced, overlaid by a single layer
of mesothelial cells. The silastic tubing was removed and at the same time, the
living tube of tissue was everted so that the mesothelium now lined its inner
surface. To examine the effect of haemodynamic factors on myofibroblast
differentiation, the 10 mm long tubes of mesothelial-lined granulation tissue
were transplanted into the severed abdominal aorta of the same rat in which the
granulation tissue was grown. End-to-end anastomoses were performed to extend the
existing aorta. At 1, 2, and 3 months post-transplantation, the grafts were
removed and a progressive increase in the percent volume fraction of myofilaments
(% V(v)myo) was observed (from 35.7+/-1.6% to 58.7 3+/-1.4%; p<0.05). To
determine whether the active stretching that occurs in vivo could account for
differentiation of the constituent myofibroblasts, tubes of granulation tissue
were placed into a mechanical device in which they underwent continuous
stretching of 5-10% elongation from the resting position at 50 cycles per minute
for 3, 24 or 72 h. This caused a significant (p<0. 05) increase in %V(v)myo after
72 h. Granulation tissue was also transplanted into the rat anterior eye chamber,
where it became surrounded by adrenergic nerves supplying the host iris. Two
months after implantation, there was no significant change in the %V(v)myo of the
myofibroblasts (35.7+/-1.6% to 33.3+/-2.7%). These studies show that
myofibroblasts of the granulation tissue encapsulating free-floating foreign
bodies in the peritoneal cavity further differentiate towards a smooth muscle
phenotype when transplanted into a smooth muscle environment, namely the
abdominal aorta. Similar changes are seen when the granulation tissue is
subjected to active, intermittent stretch in vitro, while the presence of nerves
has no effect.
PMID- 11004706
TI - [The previous law concerning infectious diseases and the new infectious diseases
control law - the problems for the enforcement of the new infectious diseases
control law in medical situation].
PMID- 11004705
TI - Role of macrophage scavenger receptor in endotoxin shock.
AB - Lipopolysaccharide (LPS) is known to bind to several receptors on macrophages,
including CD14 and macrophage scavenger receptor class A types I and II (MSR-A),
and stimulates macrophages to release various inflammatory mediators. MSR-A
recognizes a broad range of polyanionic ligands such as chemically modified
lipoproteins, LPS of Gram-negative bacteria, and lipoteichoic acid of Gram
positive bacteria, suggesting a role in host defence. In this study, mice lacking
MSR-A were used to elucidate the role of MSR-A in endotoxin shock. Peritoneal
macrophages from MSR-A-deficient (MSR-A(-/-)) mice bound less remarkably to LPS
than those from wild-type (MSR-A(+/+)) mice and the binding activity of MSR
A(+/+) macrophages to LPS was reduced by the addition of an anti-MSR-A antibody.
Clearance of LPS in serum was retarded in MSR-A(-/-) mice after intraperitoneal
administration of LPS. LPS-induced expression of cytokines in the liver was
similar in MSR-A(+/+) and MSR-A(-/-) mice, but levels of interleukin (IL)-1beta
expression and serum IL-1beta were lower in MSR-A(-/-) mice. Administration of
large doses of LPS resulted in a higher mortality of MSR-A(+/+) mice and
pretreatment with an IL-1 receptor antagonist reduced the mortality. Thus, MSR-A
mediated macrophage activation plays a negative role in protecting mice from
endotoxin shock by enhancing IL-1beta production by macrophages.
PMID- 11004707
TI - [Comparative evaluation of BACTEC MGIT 960 system with MB/BacT and egg-based
media for recovery of mycobacteria].
AB - Fully automated, nonradiometric mycobacteria culture systems, BACTEC MGIT 960
(Becton Dickinson Microbiology Systems, Sparks, Md, U.S.A.) and MB/BacT (Organon
Teknika, Durham, NC, U.S.A.) were evaluated in comparison with three different
eggbased media (3% Ogawa, Ogawa K, and Vite) for the ability to detect
mycobacteria in clinical sputum specimens. Sputum specimens were processed by
semi-alkaline protease-N-acetyl-L-cysteine-NaOH (SAP-NALC-NaOH) for the automated
systems, and by cetylpyridium chloride-succinic acid-NaCl for the egg-based
media. A total of 954 sputum specimens were processed, and the recovery of
mycobacteria by the BACTEC MGIT 960 was performed in a commercial laboratory.
Overall, the frequency of breakthrough contamination was <1% for the three egg
based media, ranging from 0. 42% to 0.63%. Whereas, the frequency of false
positives due to breakthrough contamination was 1.89% for MB/BacT and 20.1% for
BACTEC MGIT 960. A total of 237 isolates of Mycobacterium tuberculosis complex
and 167 isolates of nontuberculous mycobacteria (NTM) were recovered. The highest
recovery ratio was obtained by MB/BacT (95.8%), followed by the egg-based media,
Vite (74.3%), Ogawa K (65.8%), and 3% Ogawa (58.9%). The recovery ratio by BACTEC
MGIT 960 was the lowest, and estimated at 43.1%, mainly due to a high frequency
of breakthrough contamination. However, even after omission of these false
positives reported by BACTEC MGIT 960, the recovery ratio by this system was
comparable to that of 3% Ogawa media. The time to detection of 50% of positive
cultures of M. tuberculosis complex by BACTEC MGIT 960 and MB/BacT was 20 days
and 17 days, respectively.>From these results, it may be concluded that MB/BacT
is superior to BACTEC MGIT 960 and egg-based media for the recovery of
mycobacteria from sputum specimens. Furthermore, based on the outcome of this
study, we think that considerable improvements are necessary for the clinical
application of BACTEC MGIT 960. These improvements should particularly be focused
on reducing the false positive ratio caused by contamination, and culture media,
which effectively support mycobacterial growth.
PMID- 11004708
TI - [Evaluation of "Helicobacter-Selective-Medium (Nissui Seiyaku)" for rapid
detection of Helicobacter pylori].
AB - We evaluated Helicobacter Selective Agar (HSA) medium (Nissui Pharmaceuticals
Co., Ltd., Tokyo, Japan), which has been newly developed and has been
commercially available since June in 1998. HSA medium strongly inhibited the
growth of possible contaminants from gastric biopsy-specimens, such as alpha
streptococci, Neisseria species, Enterococcus gallinarum, Pseudomonas aeruginosa,
Corynebacterium species, Capnocytophaga species, and Candida albicans. Cultures
run in parallel with Helicobacter Pylori Agar (HPA) medium (Eiken Chemical Co.,
Ltd., Tokyo, Japan) disclosed no discordance in the detective rates of H. pylori
strains between the media examined. Inaddition, the numbers of the colonies and
the colony-sizes grown on the plates were also in good agreement with each other.
However, it would be strikingly favorable that the appearing colonies on the HSA
medium turned purple. This coloration enabled us to detect the emergence of the
colonies much earlier and easier when compared with the conventional other media
including HPA medium (Eiken). These findings led us to conclude that HSA medium
(Nissui) was superior to HPA medium (Eiken) in the prompt detection and the rapid
identification of H. pylori in routine clinical microbiology.
PMID- 11004709
TI - Preventive procedures against GBS infection by means of antibody measurement.
AB - OBJECTIVE: Screening group B Streptococcus (GBS) in the vagina of pregnant women
and measuring serum level of its type-specific antibody would be useful for cost
benefit of the prevention against GBS infection. STUDY DESIGN: The subjects
included a total of 1,150 pregnant women who consented to the study. Serotypes of
GBS detected were classified with antiserum. Serum type-specific antibody titers
were measured by a bacterial agglutination method. RESULTS: Of a total of 1,150
pregnant women, 250 cases (21.7%) had GBS in the vagina. The turn of GBS serotype
occurrence was types VI (NT6) (27. 2%), VIII (JM9) (25.2%), III (11.2%), Ia
(8.8%), and Ib (8.0%). None or low type-specific antibody titer was 41.0% of Ia,
20.0% of Ib, 22. 0% of II, 15.0% of III, 65.0% of VI, and 69.0% of VIII
incarriers. Noneonatal GBS infection occurred under the empirically treatment.
CONCLUSION: The measurement of serum type-specific antibody against GBS would be
informative for the cost-benefit treatment of the vaginal GBS in pregnant women.
PMID- 11004710
TI - Basic studies on group B streptococcal (GBS) culture medium.
AB - Yeast extract and Serum are said to be necessary for the pigmentation of Group B
Streptococcus (hereafter, GBS). We're examined the necessity of these for the GBS
pigmentation. Firstly, we examined the following four types of culture media. (1)
The medium in which serum was excluded from the New Granada medium (hereafter,
called Basic medium). (2) New Granada medium (hereafter, S medium). (3) The
medium in which Yeast extract was added to (1) (hereafter, Y medium). (4) The
medium in which added Serum and Yeast extract were added to (1) (hereafter, SY
medium). As for GBS tested (7 serotypes, 27 strains), Basic medium showed the
strongest pigmentation potency, but, S and SY medium showed the weakest. About
the quickness of pigmentation initiation, similar to the potency above, Basic
medium was the quickest, followed by Y medium, and then S medium and SY medium.
Among the media examined, there were no differences in the relationships between
the quantity of GBS applied and the positive ratio of each media.>From these
results, among four types of the media, Basic medium is thought to be the best
one for the GBS detection.
PMID- 11004711
TI - [Application of DNA-DNA hybridization, DDH MYCOBACTERIA 'Kyokuto' to species
identification of mycobacteria grown in Middlebrook 7H9 broth].
AB - A colorimetric DNA-DNA hybridization for the genetic identification of
mycobacteria, DDH MYCOBACTERIA 'KYOKUTO' (Kyokuto Pharmaceuticals, Tokyo) was
evaluated for the clinical isolates of mycobacteria grown in Middlebrook 7H9
broth of MB/BacT (Organon Teknika, Durham, NC, U.S.A.). When the MB/BacT gave the
positive interpretation, 10 ml of Middlebrook 7H9 broth was collected from the
bottle. After centrifugation at 3,000 rpm for 10 min, two drops of acetone were
added to the pellet, then let it stand for one hour at the room temperature. The
air-dried pellet was resuspended in a small volume of distilled water, and
proceeded to the identification described. Of 136 clinical isolates of
mycobacteria, comprising of 76 M. tuberculosis complex and 60 nontuberculous
mycobacteria (NTM), ninety-five (70%) were correctly identified when compared to
the reference identification. Thirty (22%) isolates resulted in the unidentified
due to negative reaction throughout the test wells, and the remaining 11 (8%)
were also unidentified due to low likelihoods. According to the package insert,
the DDH MYCOBACTERIA may not be applicable to the isolates grown in Middlebrook
broth. However, our test procedure using acetone prior to the extraction of
bacterial DNA enables us to directly identify the isolates of mycobacteria grown
in Middlebrook 7H9 broth of MB/BacT.
PMID- 11004712
TI - Role of the hypothalamic pituitary adrenal axis in the control of the response to
stress and infection.
AB - The release of adrenocorticotropin (ACTH) from the corticotrophs is controlled
principally by vasopressin and corticotropin-releasing hormone (CRH). Oxytocin
may augment the release of ACTH under certain conditions, whereas atrial
natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit
ACTH release by direct action on the pituitary. Glucocorticoids act on their
receptors within the hypothalamus and anterior pituitary gland to suppress the
release of vasopressin and CRH and the release of ACTH in response to these
neuropeptides. CRH neurons in the paraventricular nucleus also project to the
cerebral cortex and subcortical regions and to the locus ceruleus (LC) in the
brain stem. Cortical influences via the limbic system and possibly the LC augment
CRH release during emotional stress, whereas peripheral input by pain and other
sensory impulses to the LC causes stimulation of the noradrenergic neurons
located there that project their axons to the CRH neurons stimulating them by
alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed
between the alpha-receptors and nitric oxidergic interneurons which release
nitric oxide that activates CRH release by activation of cyclic guanosine
monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release
during stress may be similarly mediated. Vasopressin augments the release of CRH
from the hypothalamus and also augments the action of CRH on the pituitary. CRH
exerts a positive ultrashort loop feedback to stimulate its own release during
stress, possibly by stimulating the LC noradrenergic neurons whose axons project
to the paraventricular nucleus to augment the release of CRH.
PMID- 11004713
TI - Proliferative signaling initiated in ACTH receptors.
AB - This article reviews recent results of studies aiming to elucidate modes of
integrating signals initiated in ACTH receptors and FGF2 receptors, within the
network system of signal transduction found in Y1 adrenocortical cells. These
modes of signal integration should be central to the mechanisms underlying the
regulation of the G0-->G1-->S transition in the adrenal cell cycle. FGF2 elicits
a strong mitogenic response in G0/G1-arrested Y1 adrenocortical cells, that
includes a) rapid and transient activation of extracellular signal-regulated
kinases-mitogen-activated protein kinases (ERK-MAPK) (2 to 10 min), b)
transcription activation of c-fos, c-jun and c-myc genes (10 to 30 min), c)
induction of c-Fos and c-Myc proteins by 1 h and cyclin D1 protein by 5 h, and d)
onset of DNA synthesis stimulation within 8 h. ACTH, itself a weak mitogen,
interacts with FGF2 in a complex manner, blocking the FGF2 mitogenic response
during the early and middle G1 phase, keeping ERK-MAPK activation and c-Fos and
cyclin D1 induction at maximal levels, but post-transcriptionally inhibiting c
Myc expression. c-Fos and c-Jun proteins are mediators in both the strong and the
weak mitogenic responses respectively triggered by FGF2 and ACTH. Induction of c
Fos and stimulation of DNA synthesis by ACTH are independent of PKA and are
inhibited by the PKC inhibitor GF109203X. In addition, ACTH is a poor activator
of ERK-MAPK, but c-Fos induction and DNA synthesis stimulation by ACTH are
strongly inhibited by the inhibitor of MEK1 PD98059.
PMID- 11004714
TI - The neuroimmune-endocrine axis: pathophysiological implications for the central
nervous system cytokines and hypothalamus-pituitary-adrenal hormone dynamics.
AB - Cytokines are molecules that were initially discovered in the immune system as
mediators of communication between various types of immune cells. However, it
soon became evident that cytokines exert profound effects on key functions of the
central nervous system, such as food intake, fever, neuroendocrine regulation,
long-term potentiation, and behavior. In the 80's and 90's our group and others
discovered that the genes encoding various cytokines and their receptors are
expressed in vascular, glial, and neuronal structures of the adult brain. Most
cytokines act through cell surface receptors that have one transmembrane domain
and which transduce a signal through the JAK/STAT pathway. Of particular
physiological and pathophysiological relevance is the fact that cytokines are
potent regulators of hypothalamic neuropeptidergic systems that maintain
neuroendocrine homeostasis and which regulate the body's response to stress. The
mechanisms by which cytokine signaling affects the function of stress-related
neuroendocrine systems are reviewed in this article.
PMID- 11004715
TI - Familial hyperaldosteronism.
AB - Aldosterone, the major circulating mineralocorticoid, participates in blood
volume and serum potassium homeostasis. Primary aldosteronism is a disorder
characterised by hypertension and hypokalaemia due to autonomous aldosterone
secretion from the adrenocortical zona glomerulosa. Improved screening
techniques, particularly application of the plasma aldosterone:plasma renin
activity ratio, have led to a suggestion that primary aldosteronism may be more
common than previously appreciated among adults with hypertension. Glucocorticoid
remediable aldosteronism (GRA) was the first described familial form of
hyperaldosteronism. The disorder is characterised by aldosterone secretory
function regulated chronically by ACTH. Hence, aldosterone hypersecretion can be
suppressed, on a sustained basis, by exogenous glucocorticoids such as
dexamethasone in physiologic range doses. This autosomal dominant disorder has
been shown to be caused by a hybrid gene mutation formed by a crossover of
genetic material between the ACTH-responsive regulatory portion of the 11ss
hydroxylase (CYP11B1) gene and the coding region of the aldosterone synthase
(CYP11B2) gene. Familial hyperaldosteronism type II (FH-II), so named to
distinguish the disorder from GRA or familial hyperaldosteronism type I (FH-I),
is characterised by autosomal dominant inheritance of autonomous aldosterone
hypersecretion which is not suppressible by dexamethasone. Linkage analysis in a
single large kindred, and direct mutation screening, has shown that this disorder
is unrelated to mutations in the genes for aldosterone synthase or the
angiotensin II receptor. The precise genetic cause of FH-II remains to be
elucidated.
PMID- 11004716
TI - Plasma metanephrines: a novel and cost-effective test for pheochromocytoma.
AB - Pheochromocytomas are rare chromaffin cell tumors that nevertheless must be
excluded in large numbers of patients who develop sustained or episodic
hypertension as well as in many others with suggestive symptoms or with a
familial history of pheochromocytoma. Diagnosis of pheochromocytoma depends
importantly on biochemical evidence of excess catecholamine production by a
tumor. Imperfect sensitivity and specificity of commonly available biochemical
tests and the low incidence of the tumor among the tested population mean that
considerable time and effort can be expended in confirming or ruling out
pheochromocytoma in patients where the tumor is suspected. Measurements of plasma
free metanephrines provide a superior test compared to other available tests for
diagnosis of pheochromocytoma. In particular, the high sensitivity of plasma free
metanephrines means that a normal test result reliably excludes all but the
smallest of pheochromocytomas so that no other tests are necessary. Measurements
of plasma free metanephrines, when systematically combined with other diagnostic
procedures outlined in this review, provide a more efficient, reliable and cost
effective approach for diagnosis of pheochromocytoma than offered by previously
available approaches.
PMID- 11004718
TI - Adrenal incidentaloma.
AB - Incidentally discovered adrenal masses, or adrenal incidentalomas, have become a
common clinical problem owing to wide application of radiologic imaging
techniques. This definition encompasses a heterogeneous spectrum of pathologic
entities, including primary adrenocortical and medullary tumors, benign or
malignant lesions, hormonally active or inactive lesions, metastases, and
infections. Once an adrenal mass is detected, the clinician needs to address two
crucial questions: is the mass malignant, and is it hormonally active? This
article provides an overview of the diagnostic clinical approach and management
of the adrenal incidentaloma. Mass size is the most reliable variable to
distinguish benign and malignant adrenal masses. Adrenalectomy should be
recommended for masses greater than 4.0 cm because of the increased risk of
malignancy. Adrenal scintigraphy has proved useful in discriminating between
benign and malignant lesions. Finally, fine-needle aspiration biopsy is an
important tool in the evaluation of oncological patients and it may be useful in
establishing the presence of metastatic disease. The majority of adrenal
incidentalomas are non-hypersecretory cortical adenomas but an endocrine
evaluation can lead to the identification of a significant number of cases with
subclinical Cushing's syndrome (5-15%), pheochromocytoma (1.5-13%) and
aldosteronoma (0-7%). The first step of hormonal screening should include an
overnight low dose dexamethasone suppression test, the measure of urinary
catecholamines or metanephrines, serum potassium and, in hypertensive patients,
upright plasma aldosterone/plasma renin activity ratio. Dehydroepiandrosterone
sulfate measurement may show evidence of adrenal androgen excess.
PMID- 11004717
TI - Salivary cortisol as a tool for physiological studies and diagnostic strategies.
AB - Salivary cortisol is an index of plasma free cortisol and is obtained by a
noninvasive procedure. We have been using salivary cortisol as a tool for
physiological and diagnostic studies, among them the emergence of circadian
rhythm in preterm and term infants. The salivary cortisol circadian rhythm in
term and premature infants was established between 8 and 12 postnatal weeks. In
the preterm infants the emergence of circadian rhythm was parallel to the onset
of sleep rhythm. We also studied the use of salivary cortisol for screening for
Cushing's syndrome (CS) in control and obese outpatients based on circadian
rhythm and the overnight 1 mg dexamethasone (DEX) suppression test. Salivary
cortisol was suppressed to less than 100 ng/dl after 1 mg DEX in control and
obese patients. A single salivary cortisol measurement at 23:00 h and again after
1 mg DEX above the 90th percentile of the obese group values had sensitivity and
specificity of 93 and 93% (23:00 h), and 91 and 94% (after DEX), respectively.
The sensitivity improved to 100% when we combined both parameters. We also
studied 11 CS children and 21 age-matched primary obese children for whom
salivary cortisol sensitivity and specificity were 100/95% (23:00 h), and 100/95%
(1 mg DEX), respectively. Similar to adults, sensitivity and specificity of 100%
were obtained by combining 23:00 h and 1 mg DEX. The measurement of salivary
cortisol is a useful tool for physiological studies and for the diagnosis of CS
in children and adults on an outpatient basis.
PMID- 11004719
TI - Clinical results of the use of mitotane for adrenocortical carcinoma.
AB - Mitotane (o,p'-DDD) acts mainly as an inhibitor of intramitochondrial
pregnenolone and cortisol synthesis. Its adrenolytic effect depends on metabolic
activation due to conversion to o,p'-DDA and o,p'-DDE. The drug has been used for
40 years in the treatment of adrenocortical carcinoma, mainly its regional and
metastatic stage, as an adjuvant to surgical resection of the tumor. In the
medical literature there are controversial opinions about its efficacy for the
treatment of adrenocortical carcinoma. In our experience, mitotane administered
immediately after surgery appeared to be much more efficient than when
administered later. We have administered this drug in all cases of
microscopically confirmed adrenocortical carcinoma, irrespectively of stage at
the time of surgery, for fear of a false too optimistic classification. In our
series of 82 patients with adrenocortical carcinoma, 59 patients have been
treated with mitotane, 32 of them immediately after surgery, and 27 with a delay
of 2 to 24 months. Today there are 18 survivors in the group of patients treated
with mitotane soon after the operation and only 6 survivors in the group
receiving mitotane with a delay. All patients were simultaneously given
replacement therapy. Undesired effects of mitotane administration included
increased aminotransferase and alkaline phosphatase activity, decreased white
cell, platelet or red cell number, and myasthenia. Furthermore, we used mitotane
with good results in Cushing's syndrome of non-malignant origin as pre-treatment
before surgery or in long-term treatment for patients with poor tolerance of
other adrenal inhibitors.
PMID- 11004720
TI - Conventional and novel strategies in the treatment of adrenocortical cancer.
AB - Adrenocortical carcinoma is a highly malignant neoplasm with an incidence of two
per million people per year. Several treatment strategies have resulted in
temporary or partial tumor regression but very few cases have attained long
survival. Surgical resection of the primary tumor and metastases is most
effective. Several chemotherapeutic protocols have been employed with variable
success. Mitotane (o,p'-DDD) is an adrenalytic drug effective in inducing a tumor
response in 33% of patients treated. Mitotane requires metabolic transformation
for therapeutic action. Tumors may vary in their ability to metabolize mitotane
and the ability of tumors to transform mitotane may predict the clinical response
to the drug. Preliminary data show a possible correlation between metabolic
activity of neoplastic adrenocortical tissue and response to mitotane. We have
attempted to develop mitotane analogs with enhanced adrenalytic effect. Compared
to mitotane, a di-chloro compound, the bromo-chloro and di-bromo analogs appear
to have a greater effect. Future approaches to the treatment of adrenocortical
carcinoma are likely to be based on blocking or reversing the biological
mechanisms of tumorigenesis. Angiogenic and chemotactic mechanisms may play a
role in adrenal tumor growth and inhibition of these mechanisms may result in
inhibition of tumor growth. New mitotane analogs with greater adrenalytic
potential could be a promising approach to developing more effective and
selective therapies for adrenal cancer. Alternative approaches should attempt to
suppress tumor growth by means of compounds with anti-angiogenic and anti
chemotactic activity.
PMID- 11004721
TI - The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows
novel pharmacological therapies.
AB - Recent studies from several groups have indicated that abnormal or ectopic
expression and function of adrenal receptors for various hormones may regulate
cortisol production in ACTH-independent hypercortisolism. Gastric inhibitory
polypeptide (GIP)-dependent Cushing's syndrome has been described in patients
with either unilateral adenoma or bilateral macronodular adrenal hyperplasia;
this syndrome results from the large adrenal overexpression of the GIP receptor
without any activating mutation. We have conducted a systematic in vivo
evaluation of patients with adrenal Cushing's syndrome in order to identify the
presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we
have identified, in addition to GIP-dependent Cushing's syndrome, other patients
in whom cortisol production was regulated abnormally by vasopressin, ss
adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In
patients with unilateral adrenal adenoma, the abnormal expression or function of
GIP or vasopressin receptor has been found, but the presence of ectopic or
abnormal hormone receptors appears to be less prevalent than in macronodular
adrenal hyperplasia. The identification of the presence of an abnormal adrenal
receptor offers the possibility of a new pharmacological approach to control
hypercortisolism by suppressing the endogenous ligands or by using specific
antagonists for the abnormal receptors.
PMID- 11004722
TI - 21-Hydroxylase deficiency in Brazil.
AB - We determined the frequency of large rearrangements and point mutations in 130
Brazilian patients with 21-hydroxylase deficiency and correlated genotype with
phenotype. The frequency of CYP21 deletions was lower (4.4%) than in most of the
previous series described, whereas the frequency of large gene conversions was
similar to the frequency reported in the literature (6.6%). The most frequent
point mutations were I2 splice (41.8% in salt wasting - SW), I172N (32.6% in
simple virilizing - SV) and V281L (40.2% in the late onset form - LO). The
frequency of the nine most common point mutations was similar to that reported
for other countries. The 93 fully genotyped patients were classified into 3
mutation groups based on the degree of enzymatic activity (A<2%, B approximately
2%, C>20%). In group A, 62% of cases presented the SW form; in group B, 96% the
SV form, and in group C, 88% the LO form. We diagnosed 80% of the affected
alleles after screening for large rearrangements and 15 point mutations. To
diagnose these remaining alleles we sequenced the CYP21 gene of one patient with
the SV form and identified a heterozygous G-->A transition in codon 424. This
mutation leads to a substitution of glycine by serine in a conserved region and
was also found in a compound heterozygous state in 4 other patients. The mutation
G424S presented a linkage disequilibrium with CYP21P and C4A gene deletions and
HLA DR17, suggesting a probable founder effect. Search for the G424S mutation in
other populations will reveal if it is restricted to the Brazilian patients or if
it has a wider ethnic distribution.
PMID- 11004723
TI - Amplification of 9q34 in childhood adrenocortical tumors: a specific feature
unrelated to ethnic origin or living conditions.
AB - Adrenocortical tumors (ACT) in children under 15 years of age exhibit some
clinical and biological features distinct from ACT in adults. Cell proliferation,
hypertrophy and cell death in adrenal cortex during the last months of gestation
and the immediate postnatal period seem to be critical for the origin of ACT in
children. Studies with large numbers of patients with childhood ACT have
indicated a median age at diagnosis of about 4 years. In our institution, the
median age was 3 years and 5 months, while the median age for first signs and
symptoms was 2 years and 5 months (N = 72). Using the comparative genomic
hybridization technique, we have reported a high frequency of 9q34 amplification
in adenomas and carcinomas. This finding has been confirmed more recently by
investigators in England. The lower socioeconomic status, the distinctive ethnic
groups and all the regional differences in Southern Brazil in relation to
patients in England indicate that these differences are not important to
determine 9q34 amplification. Candidate amplified genes mapped to this locus are
currently being investigated and Southern blot results obtained so far have
discarded amplification of the abl oncogene. Amplification of 9q34 has not been
found to be related to tumor size, staging, or malignant histopathological
features, nor does it seem to be responsible for the higher incidence of ACT
observed in Southern Brazil, but could be related to an ACT from embryonic
origin.
PMID- 11004724
TI - Adrenocortical tumors in children.
AB - Childhood adrenocortical tumors (ACT) are rare. In the USA, only about 25 new
cases occur each year. In Southern Brazil, however, approximately 10 times that
many cases are diagnosed each year. Most cases occur in the contiguous states of
Sao Paulo and Parana. The cause of this higher rate has not been identified.
Familial genetic predisposition to cancer (p53 mutations) and selected genetic
syndromes (Beckwith-Wiedemann syndrome) have been associated with childhood ACT
in general but not with the Brazilian counterpart. Most of the affected children
are young girls with classic endocrine syndromes (virilizing and/or Cushing).
Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA
S), which are abnormal in approximately 90% of the cases, provide the pivotal
clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of
a large, well-defined suprarenal tumor containing calcifications with a thin
capsule and central necrosis or hemorrhage. The pathologic classification of
pediatric ACT is troublesome. Even an experienced pathologist can find it
difficult to differentiate carcinoma from adenoma. Surgery is the single most
important procedure in the successful treatment of ACT. The role of chemotherapy
in the management of childhood ACT has not been established although occasional
tumors are responsive to mitotane or cisplatin-containing regimens. Because of
the heterogeneity and rarity of the disease, prognostic factors have been
difficult to establish in pediatric ACT. Patients with incomplete tumor resection
or with metastatic disease at diagnosis have a dismal prognosis. In patients with
localized and completely resected tumors, the size of the tumor has predictive
value. Patients with large tumors have a much higher relapse rate than those with
small tumors.
PMID- 11004726
TI - The expression of the ACTH receptor.
AB - Adrenal glucocorticoid secretion is regulated by adrenocorticotropic hormone
(ACTH) acting through a specific cell membrane receptor (ACTH-R). The ACTH-R is a
member of the G protein superfamily-coupled receptors and belongs to the
subfamily of melanocortin receptors. The ACTH-R is mainly expressed in the
adrenocortical cells showing a restricted tissue specificity, although ACTH is
recognized by the other four melanocortin receptors. The cloning of the ACTH-R
was followed by the study of this gene in human diseases such as familial
glucocorticoid deficiency (FGD) and adrenocortical tumors. FGD is a rare
autosomal recessive disease characterized by glucocorticoid deficiency, elevated
plasma ACTH levels and preserved renin/aldosterone secretion. This disorder has
been ascribed to an impaired adrenal responsiveness to ACTH due to a defective
ACTH-R, a defect in intracellular signal transduction or an abnormality in
adrenal cortical development. Mutations of the ACTH-R have been described in
patients with FGD in segregation with the disease. The functional
characterization of these mutations has been prevented by difficulties in
expressing human ACTH-R in cells that lack endogenous melanocortin receptor
activity. To overcome these difficulties we used Y6 cells, a mutant variant of
the Y1 cell line, which possesses a non-expressed ACTH-R gene allowing the
functional study without any background activity. Our results demonstrated that
the several mutations of the ACTH-R found in FGD result in an impaired cAMP
response or loss of sensitivity to ACTH stimulation. An ACTH-binding study showed
an impairment of ligand binding with loss of the high affinity site in most of
the mutations studied.
PMID- 11004725
TI - Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas.
AB - Over a 15-year period, our university-based laboratory obtained 125 adrenal
tumors, of which 15 (12%) were adrenal cortical carcinomas. Of these, 6 (40% of
the carcinomas) occurred in patients with clear clinical manifestations of
steroid hormone excess. Adrenal cortical carcinoma cells derived from the
surgically resected tumors in 4 of these patients were isolated and established
in primary culture. Radiotracer steroid interconversion studies were carried out
with these cultures and also on mitochondria isolated from homogenized tissues.
Large tumors had the lowest steroidogenic activities per weight, whereas small
tumors had more moderately depressed enzyme activities relative to cells from
normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone
blocked the synthesis of corticosterone and cortisol and also the formation of
aldosterone. Metyrapone inhibition was associated with a concomitant increase in
the formation of androgens (androstenedione and testosterone) from pregnenolone.
Administration of metyrapone in vivo before surgery in one patient resulted in a
similar increase in plasma androstenedione, though plasma testosterone levels
were not significantly affected. In cultures of two of four tumors examined,
dibutyryl cAMP stimulated 11ss-hydroxylase activity modestly; ACTH also had a
significant stimulatory effect in one of these tumors. Unlike results obtained
with normal or adenomatous adrenal cortical tissues, mitochondria from
carcinomatous cells showed a lack of support of either cholesterol side-chain
cleavage enzyme complex or steroid 11ss-hydroxylase activity by Krebs cycle
intermediates (10 mM isocitrate, succinate or malate). This finding is consistent
with the concept that these carcinomas may tend to function predominantly in an
anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.
PMID- 11004727
TI - Role of ACTH receptor in adrenocortical tumor formation.
AB - Adrenocorticotrophin (ACTH) is the major regulatory hormone of steroid synthesis
and secretion by adrenocortical cells. The actions of ACTH are mediated by its
specific membrane receptor (ACTH-R). The human ACTH-R gene was recently cloned,
allowing systematic determination of its sequence, expression and function in
adrenal tumorigenesis. The presence of oncogenic mutations of the ACTH-R gene in
adrenocortical tumors has been reported. Direct sequencing of the entire coding
region of the ACTH-R gene of sporadic adrenocortical adenomas and carcinomas did
not reveal constitutive activating mutations, indicating that this mechanism is
not frequent in human adrenocortical tumorigenesis. Recent studies demonstrated
allelic loss of the ACTH-R gene in a subset of sporadic adrenocortical tumors
using a PstI polymorphism located in the promoter region of the ACTH-R gene. Loss
of heterozygosity of the ACTH-R was analyzed in 20 informative patients with a
variety of benign and malignant adrenocortical tumors. Three of them showed loss
of heterozygosity of the ACTH-R gene. In addition, Northern blot experiments
demonstrated reduced expression of ACTH-R mRNA in these three tumors with loss of
heterozygosity, suggesting the functional significance of this finding at the
transcriptional level. Deletion of the ACTH-R gene seems to be involved in a
subset of human adrenocortical tumors, contributing to cellular
dedifferentiation.
PMID- 11004728
TI - Suicide attempts in the Hungarian adult population. Their relation with DIS/DSM
III-R affective and anxiety disorders.
AB - Prevalence of suicide attempts and their relationship with DIS anxiety and
affective disorder diagnoses were investigated in a Hungarian adult community
sample. Despite the high suicide mortality rate, the rate of suicide attempts was
similar to that reported in other studies using similar methods. Suicide attempts
occurred more frequently among women and previously married persons. Although the
presence of any lifetime anxiety and/or affective disorder increased the rate of
reported suicide attempts, the effect of co-morbidity, recurrence and chronicity
might be considered significant predictors. The highest odds of an attempt were
related to the diagnoses of dysthymic or bipolar disorders. Agitation was the
only depressive symptom, which increased the odds of a suicide attempt.
PMID- 11004729
TI - Deliberate self-poisoning presenting at a rural hospital in Northern Ireland 1976
1996: relationship to prescribing.
AB - PURPOSE: This study reports on a project to monitor deliberate self-poisoning in
a rural area of Northern Ireland over a 20-year period. Comparison is made with
reports from large urban centres. In addition, a local prescribing database
allows assessment of any association between psychotropic drug prescription and
use for deliberate self-poisoning. MATERIALS AND METHODS: Frequency of self
poisoning, demographic details and drugs used were recorded for all episodes of
deliberate self-poisoning occurring at Craigavon Area Hospital for the years
1976, 1986, 1991 and 1996. It was possible to compare prescriptions of
psychotropic drugs with their use for deliberate self-poisoning between the years
1991 and 1996 in the region served by the hospital, using the Defined Daily Dose
(DDD) system. RESULTS: In this rural area the pattern of deliberate self
poisoning has changed, as in urban centres, with a rise in frequency and the
male/female ratio approaching unity. The pattern of drug use has altered, with
paracetamol overtaking benzodiazepines as the most commonly used agent. More
recently, antidepressants have become the second most frequently used drug class
for this purpose. Psychotropic medications used for self-poisoning altered in
proportion to their prescription between the years 1991 and 1996. CONCLUSIONS: In
the face of a continuing rise in deliberate self-poisoning, which is effecting
both urban and rural areas, care should be taken to prescribe the least toxic
agent available as this is associated with likely frequency of self-poisoning for
most classes of psychotropic drug.
PMID- 11004730
TI - Prevalence of subthreshold forms of psychiatric disorders in persons making
suicide attempts in Hungary.
AB - BACKGROUND: Suicide and suicide attempts have been associated to psychiatric
illnesses; however, little is known about the role in suicide risk of those
symptoms that do not meet the full criteria for a DSM-IV disorder. The aim of
this study was to examine the prevalence of subthreshold psychiatric disorders
among suicide attempters in Hungary. METHODS: Using a modified structured
interview (Mini International Neuropsychiatric Interview) determining 16 Axis I
psychiatric diagnoses and their subthreshold forms defined by the DSM-IV and a
semistructured interview collecting background information, the authors examined
140 consecutive suicide attempters, aged 18-65 years. RESULTS: Eighty-three-point
six percent of the attempters had one or more current threshold diagnoses on Axis
I and in addition more than three-quarters (78.6%) of the subjects had at least
one subthreshold diagnosis. Six-point-four percent of the subjects (N = 9) had
neither subthreshold nor threshold diagnoses at the time of their suicide
attempts. Ten percent of the subjects (N = 14), not meeting the full criteria for
any DSM-IV diagnoses, had at least one subthreshold diagnosis. In 68.6% of the
subjects (N = 96), both subthreshold and threshold disorders were diagnosed at
the time of their suicide attempts. The number of subthreshold and threshold
diagnoses were positively and significantly related (chi2 = 5.12, df = 1, P <
0.05). Sixty-three-point-six percent of the individuals received two or more
current threshold diagnoses on Axis I and 44.3% of the individuals (N = 62) had
two or more subthreshold diagnoses at the time of their suicide attempts.
LIMITATIONS: The subthreshold definitions in this study included only those forms
of the disorders which required the same duration as the criteria DSM-IV disorder
with fewer symptoms. Conclusions - Suicide attempts showed a very high prevalence
of subthreshold disorders besides psychiatric disorders meeting the full criteria
required according to the DSM-IV. Subthreshold forms of mental disorders need to
be taken into account in suicide prevention.
PMID- 11004731
TI - Evolution of the management of depression in Spain from the psychiatrist's
perspective. A comparative analysis: 1997 vs 1982.
AB - The main problem of depression is not only the high prevalence of the disorder
but also its serious consequences on the patient's quality of life and the
associated social costs in terms of health care resource utilization and
productivity losses. In recent years, there has been a considerable improvement
in the knowledge of depression from the pathogenic, clinical and therapeutic
perspectives. The present study analyzes whether such advances are reflected in a
positive evolution of the treatment of depression in Spain. To this effect we
have contrasted the results of two socio-sanitary studies published in this
country: the White Book editions of 1982 and 1997 (WB82 and WB97, respectively).
From the methodological perspective, the physician selection criteria employed
were very uniform (structured questionnaires delivered to 128 (WB82) and 300
(WB97) randomly selected psychiatrists). The origin of patients consulting for
specialized care has varied over this 15-year period. In effect, WB82 patients
were essentially referred by friends (87.5%) and from the primary care setting
(44.5%), whereas in the WB97 study referral from primary care predominated
(50.1%), followed by the patient's personal decision (24.8%). In turn, 40.7% and
51.7% of the psychiatrists in WB97 respectively considered the diagnostic and
therapeutic means available in primary care to be insufficient. The priorities
for improving patient quality of life, as reflected by both editions of the
study, were the training of primary care physicians and the adequate provision of
means in the mental health care centers. On the other hand, fewer problems for
establishing a correct diagnosis were referred in the 1997 edition of the study
(28.7%) than in 1982 (48.4%). In this sense, the main problem reported in WB82
was the lack of specialized training, whereas the masking of depression by some
other disease process or symptoms was the main problem in WB97 (67.6% vs 21.1%
according to WB82). The main symptoms upon which the diagnosis of depression are
based do not seem to have evolved much in the past 15 years. The most frequently
cited manifestations were a worsening of mood, loss of interest and leisure
capacity, sleep alterations and diminished vitality. A comparative analysis of
the therapeutic resources used was not possible, for prior to 1982 the only drugs
available to physicians were the classical tricyclic agents and some MAO
inhibitors; the selective serotonin reuptake inhibitors (SSRIs) - possibly the
greatest advance in the treatment of depression in these 15 years - had not yet
been introduced. Nevertheless, it should be pointed out that 98% of the
psychiatrists consulted in WB97 considered pharmacologic treatment to be the most
widely adopted form of management once depression has been diagnosed.
PMID- 11004732
TI - P300 event-related brain potential and personality in depression.
AB - P300 is an event-related brain potential (ERP) particularly interesting to the
study of cognitive processes in normal subjects and in psychopathology. P300 has
been applied in depression with controversial results. A major source for these
controversial results could result from the diversity of depressed patients
included in the different studies. Supporting this assumption, impulsivity,
blunted affect, suicidal behavior and psychotic features significantly influence
P300 amplitude. However, no data are available on the possible influences of the
personality of depressed patients on P300. Since personality is related to P300
in normal subjects, the aim of the present study is to investigate the
relationship between ERPs (P200, N200, and P300) and the Temperament and
Character Inventory (TCI) in 54 depressed patients. The main results of the study
concern the absence of major correlations between personality dimensions as
assessed by the TCI and ERP parameters among depressed patients. Only weak
partial positive correlations relate N200 latency with harm avoidance, and P300
amplitude (Pz) with the self-directedness dimension. N200 amplitude is also
negatively correlated to persistence. However, the preliminary nature of the
presented results with respect to the weak statistical significance should be
underlined.
PMID- 11004733
TI - Economic impact of using mirtazapine compared to amitriptyline and fluoxetine in
the treatment of moderate and severe depression in the UK.
AB - This study modelled the economic impact of mirtazapine, compared to amitriptyline
and fluoxetine, in the management of moderate and severe depression in the UK, as
well as the costs related to discontinuation of antidepressant treatment.
Decision models of the management of moderate and severe depression were
developed from clinical trial data, resource use obtained from interviews with
general practitioners and psychiatrists, and published literature, and were used
to estimate the expected direct National Health Service (NHS) costs of managing a
patient with moderate or severe depression. The expected cost of healthcare
resource use attributable to managing a patient suffering from moderate or severe
depression who discontinues antidepressant treatment, irrespective of the initial
treatment, was estimated to be pounds sterling 206 (range pounds sterling 50 to
pounds sterling 504) over five months. Using mirtazapine instead of amitriptyline
for seven months increases the proportion of successfully treated patients by 21%
(from 19.2 to 23.2%) and reduces the expected direct NHS cost by pounds sterling
35 per patient (from pounds sterling 448 to pounds sterling 413). Using
mirtazapine instead of fluoxetine for six months increases the proportion of
successfully treated patients by 22% (from 15.6 to 19.1%), albeit for an
additional cost to the NHS of pounds sterling 27 per patient (from pounds
sterling 394 to pounds sterling 420). In conclusion, this study suggests that
mirtazapine is a cost-effective antidepressant compared to amitriptyline and
fluoxetine in the management of moderate and severe depression in the UK.
PMID- 11004734
TI - Beneficial effect of the addition of the 5-HT 2A/2C and alpha2 antagonist
mianserin to ongoing haloperidol treatment in drug-resistant chronically
hospitalized schizophrenic patients.
AB - Atypical neuroleptics that block serotonin 2A (5-HT 2A) and dopamine 2 (D2)
receptors have been shown to possess efficacious antipsychotic activity. We
assessed the efficacy of the addition of the 5-HT 2A/2C and alpha2 antagonist
mianserin to ongoing haloperidol treatment in chronically hospitalized (> 10
years) drug-resistant schizophrenic patients (N = 12). The patients were assessed
at baseline and every three months for one year with the Brief Psychiatric Rating
Scale and the Clinical Global Impression. Results showed a significant (but <
10%) improvement in the core symptoms of schizophrenia; however, only the
reduction (by 43%) in anxiety was clinically relevant (P < 0.0001). The
beneficial effect of mianserin may be related to the combined blockade of 5-HT 2A
and histamine (H1) receptors.
PMID- 11004735
TI - Are washout periods useful in antidepressant trials?
PMID- 11004736
TI - Protection from extinction in human fear conditioning.
AB - Two experiments examined the ability of an added stimulus to interfere with
extinction of a target excitatory fear stimulus (a predictor of shock) in human
autonomic conditioning. Both experiments demonstrated disruption of extinction
when the added stimulus was inhibitory (a predictor of no shock, or safety
signal). Subjects showed a return of fear when the target stimulus was tested
alone, on both self-reported shock expectancy and skin conductance measures. The
second experiment also demonstrated disruption of extinction when the added
stimulus was excitatory. This results suggests that protection from extinction
may occur even when the added stimulus is not inhibitory. Additional factors that
may contribute to protection from extinction include context-specificity,
occasion-setting and external inhibition. The results highlight the role that
concurrent stimuli play in extinction, and emphasise the need to keep concurrent
stimuli as similar as possible to the desired transfer context in practical
applications of extinction such as exposure therapy for anxiety.
PMID- 11004737
TI - Does the social concerns component of the anxiety sensitivity index belong to the
domain of anxiety sensitivity or the domain of negative evaluation sensitivity?
AB - The present study utilized an exploratory factor-analytic approach (i.e.
principal-components analysis; PCA) to investigate whether the Social Concerns
component of the Anxiety Sensitivity Index (ASI [Peterson, R. A., & Reiss, S.
(1992). Anxiety Sensitivity Index manual (2nd ed.). Worthington, OH:
International Diagnostic Systems.]) is best conceptualized as belonging to the
domain of anxiety sensitivity (AS) and/or the domain of negative evaluation
sensitivity (NES). A sample of university students (N = 216) was administered
measures of both NES (i.e. Brief Fear of Negative Evaluation scale; Leary, 1983)
and AS (i.e. ASI). Participants' responses to the items comprising these measures
were subjected to a PCA with oblique rotation. Factors representing the NES
construct and the three lower-order AS constructs (i.e. AS Physical,
Psychological and Social Concerns) were obtained. Subscales derived from these
four factors were positively and significantly correlated with one another and
loaded on a single higher-order factor labeled Threat Sensitivity. Thus, the
present findings suggest that the AS Social Concerns factor is distinct from NES
and the other lower-order components of AS. However, correlational analyses and
higher-order PCA indicated that the AS Social Concerns factor taps a blend of AS
and NES as well as something unique and distinct from both global AS and NES.
PMID- 11004738
TI - Challenging the omnipotence of voices: group cognitive behavior therapy for
voices.
AB - The present study examines the impact of group based cognitive behavior therapy
(CBT) for drug resistant auditory hallucinations, or voices. In particular it
assesses treatment effect on beliefs in a voice's omnipotence and control. Twenty
two participants entered one of five 8-session CBT groups. Measures of
omnipotence, control, process measures, and symptoms of anxiety and depression
were completed at assessment, and first and last group sessions. The groups
achieved a significant reduction in conviction in beliefs about omnipotence (df
2, P = 0.002) and control (df 2, P = 0.001). There were no affective changes.
Certain participants showed important spontaneous changes in behavior. Process
measures suggested that participants valued the groups and benefited from them.
These results are promising and the treatment may prove a useful addition to
existing psychological interventions.
PMID- 11004739
TI - Excessive breathlessness through emotional imagery in asthma.
AB - Breathlessness and negative emotions during asthma attacks interact in complex
patterns. This study tested the influence of emotional imagery on breathlessness
during voluntary breath holding. Adolescents with and without asthma (n = 36 +
36) were assigned to positive imagery, negative imagery, or no imagery. There
were four trials with close to thresholds for breath holding combined with
imagery. Breathlessness and quality of imagery were measured by the end of breath
holding. Additional measures were lung function and anxiety. The results showed
that positive and negative imagery were only influencing breathlessness in
participants with asthma. Although threshold duration for the groups were not
significantly different, participants with asthma reported more breathlessness.
The intensity of imagery enhanced breathlessness but diminished the accuracy of
symptom perception. Positive imagery diminished breathlessness in participants
with asthma, but also the difference in breathlessness between 75% and 95% of
threshold duration. Breathlessness did not correlate with lung function, anxiety
or other variables. It was concluded that emotional imagery during asthma attacks
distracts from accurate introspection or enhances breathlessness, irrespective of
anxiety.
PMID- 11004740
TI - Posttraumatic stress disorder in breast cancer patients following autologous bone
marrow transplantation or conventional cancer treatments.
AB - We assessed 17 women who had undergone autologous bone marrow transplants (BMT)
for their breast cancer and 20 other women who had been treated for breast cancer
(but not with BMT) by structured clinical interviews examining each stage of the
breast cancer experience (e.g. initial diagnosis, initial treatment, recurrence
of cancer (if applicable) and BMT (if applicable)) and at follow-up points; 3, 6
and 12 months (if applicable) posttreatment. The two groups did not differ on
incidence of posttraumatic stress disorder (PTSD), major depressive disorder
(MDD) or generalized anxiety disorder at any stage. We found a high rate of PTSD
over the cancer experience, 35% for the combined sample, with cancer diagnosis
being the most likely point for developing PTSD, 27% for the combined sample.
None of the 17 women who had undergone BMT developed PTSD as a result of the
treatment.
PMID- 11004741
TI - The relationship between inflated personal responsibility and exaggerated danger
expectancies in obsessive-compulsive concerns.
AB - The association between responsibility for a negative outcome, perceived severity
of the outcome and perceived likelihood of the outcome was examined in a sample
of 70 undergraduate students. Participants were asked to rate the likelihood and
severity of 10 negative outcomes, five related to contamination and five related
to checking. Thirty-eight participants completed a version of the questionnaire
that presented the subject as responsible for the action that may lead to a
negative outcome ('personally responsible' group). The remaining 32 completed a
version of the questionnaire that presented someone else performing the actions
that may lead to a negative outcome ('other responsible' group). Significant
differences emerged between the personally responsible and other responsible
groups for severity of outcome ratings but not for likelihood of outcome ratings.
Specifically, for both washing and checking concerns, participants in the
personally responsible group rated the severity of the potential negative outcome
as greater than did those in the other responsible group. The results support the
claimed general tendency for individuals to regard an outcome as more aversive if
they are personally responsible for that outcome, rather than someone else being
responsible. The results suggest that, in general, increasing perceptions of
personal responsibility will increase cost or severity estimates in subjective
danger calculations, and that responsibility may influence OCD phenomena in this
way. Finally, the results suggest that attempts to manipulate responsibility in
the laboratory may be confounded by necessarily impacting on cost estimates, and
therefore on danger expectancies.
PMID- 11004742
TI - The cardiac anxiety questionnaire: development and preliminary validity.
AB - Heart-focused anxiety (HFA) is the fear of cardiac-related stimuli and sensations
because of their perceived negative consequences. Although HFA is common to a
wide variety of persons who experience chest pain and distress, it often is
unrecognized and misdiagnosed, particularly in cardiology and emergency room
patients without and with heart disease. To address these concerns, this article
reports on the development and preliminary psychometric evaluation of the Cardiac
Anxiety Questionnaire (CAQ) designed to measure HFA. In Study 1, 188 cardiology
patients completed the CAQ. Item and factor analyses indicated a three-factor
solution pertaining to heart-related fear, avoidance, and attention. Reliability
analysis of the 18-item CAQ revealed good internal consistency of the total and
subscale scores. In Study 2, 42 patients completed the CAQ and several other
anxiety-related questionnaires to assess its convergent and divergent properties.
Although preliminary validity results are promising, further psychometric study
is necessary to cross-validate the CAQ, examine its test-retest reliability, and
confirm the stability of the factor structure. Taken together, the CAQ appears to
assess HFA, and may therefore be a useful instrument for identifying patients
with elevated HFA without and with heart disease.
PMID- 11004743
TI - [Study of the brain involuntary syntactic processing by positron emission
tomography].
PMID- 11004744
TI - [Effect of glycine on EEG parameters and the sensorimotor activity in normal and
alcoholic subjects].
PMID- 11004745
TI - [Amplitude modulation of EEG in humans].
PMID- 11004746
TI - [Right and left hemispheres in the emotional evaluation of visual stimuli].
PMID- 11004747
TI - [Dependence of the threshold of sinusoidal grating displacement on its spatial
frequency characteristics].
PMID- 11004748
TI - [Study of latent periods of visual object differentiation using various
significant characteristics].
PMID- 11004749
TI - [Regulation of blood circulation in hypertonic crises using mathematical analysis
of the heart rhythm].
PMID- 11004750
TI - [Analysis of the heart rhythm variability in negative functional states during
sessions of psychological relaxation].
PMID- 11004751
TI - [Effect of extralow frequency variations of atmospheric pressure on voluntary
attention parameters].
PMID- 11004752
TI - [Electrical activity of the triceps sural muscle under static load in patients
with chronic peripheral circulatory insufficiency].
PMID- 11004753
TI - [Effect of various regimes of interval hypoxic training on cardiorespiratory and
hematologic functions].
PMID- 11004754
TI - [The role of thoracic and abdominal components of the respiratory system during
hyperventilation combined with chemoreceptor stimulation of various intensity].
PMID- 11004756
TI - [Circadian rhythms of salivary cortisol level during long-term space flight].
PMID- 11004755
TI - [Physical working capacity and its determining factors during 120 day
antiorthostatic hypokinesia].
PMID- 11004757
TI - [Microrheological properties of various erythrocyte populations in patients with
elevated blood pressure and in physically active subjects].
PMID- 11004758
TI - [Constitutional characteristics of response of hemostasis to the physical load].
PMID- 11004759
TI - [Does the respiratory system limit the human aerobic work capacity?].
PMID- 11004760
TI - [Does the 48-hour biological rhythm exist?].
PMID- 11004761
TI - [Reaction time during perception of acoustic models of sound approaching and
withdrawing under backward masking conditions].
PMID- 11004762
TI - [Interhemisphere interactions during bimanual backward masking].
PMID- 11004763
TI - [Sex difference in the electrodermal activity under various wakefulness
conditions].
PMID- 11004764
TI - [Constitutional aspects of psychoemotional stresses in adolescents].
PMID- 11004765
TI - [Living donor liver transplantation in Kyushu University].
AB - We performed living donor liver transplantation (LDLT) for 40 patients at Kyushu
University Hospital, Fukuoka Japan during the period from October 1996 to April
2000. The patients consisted of 32 adults and 8 children with a mean age of 35.8
years (range: 1 year and 10 months to 65 years old). The underlying liver
diseases of the 40 patients included the fulminant hepatic failure (n = 14),
biliary atresia (n = 7), liver cirrhosis (HCV) (n = 6), primary biliary cirrhosis
(n = 5), primary sclerosing cholangitis (n = 2), familiar amyloidotic
polyneuropathy (n = 2), Alagille syndrome (n = 1), glycogen storage disease (n =
1), huge hepatic hemangiomas (n = 1), and Wilson's disease (n = 1). All liver
grafts were obtained from each patient's family members except for one domino
transplant donor's case, comprised of 13 parents, 13 sons and daughters, 11
brothers and sisters, and 3 wives. The donors are presently all doing well. The
patient survival rate is presently 92.5%.
PMID- 11004766
TI - [Lung cancer risk and genetic polymorphism at the glutathione S-transferase P1
locus in male Japanese].
AB - The glutathione S-transferases (GSTs) are widely expressed in mammalian tissues
and involved in Phase II detoxification reactions. The GSTs form a supergene
family consisting of four distinct families, named alpha (GSTA), mu (GSTM) theta
(GSTT) and pi (GSTP). Several of the GST genes are polymorphic in humans and are
currently being investigated as possible cancer-risk modifiers. Among the GST
genes, we examined GSTP1 polymorphism in exon 5 among male lung cancer patients
(n = 86, male Japanese) and male healthy controls (n = 80, male Japanese) by
restriction fragment length polymorphism-polymerase chain reaction method. The
cancer patients showed frequency of the GSTP1 mutated genotype (individuals
having at least one mutant allele, 29.1%) very similar to that of the control
subjects (28.8%). After adjusting for smoking status, no association was found
between the GSTP1 mutated genotype and lung cancer risk (odds ratio: 0.95; 95%
confidence interval: 0.48-1.90). When study subjects were divided into two
subgroups based on smoking status, the GSTP1 mutated genotype was not associated
with an increased risk of lung cancer among smokers and non-smokers. These
results suggest that GSTP1 polymorphism in exon 5 alone may not increase the risk
of lung cancer in male Japanese.
PMID- 11004767
TI - Life's many pieces: the identity of the group psychotherapist.
AB - The American Group Psychotherapy Association (AGPA) and its members are
experiencing a trauma in response to the changes in health care imposed by the
managed care industry. Although the economic threat is frightening, the threat to
professionals' and AGPA's identities is even more damaging. The increasingly
rapid, society-wide rate of change and factors related to the aging of AGPA's
membership complicate its ability to cope with the trauma. The author recounts
personal trauma and professional experiences in treating traumatized individuals,
and proposes that when certain needs are met, growth can occur as part of a
healing process: getting through the trauma, finding safety, self-soothing, and
achieving mastery. AGPA resources for being safe, self-soothing, and achieving
mastery are described. AGPA has been successful in reaching out via new
accomplishments in regard to visibility, although the understandable impulse to
withdraw may be impeding efforts to diversify the membership body. The author
urges fighting against the pull to withdraw and expresses hope that the AGPA will
cope well with the trauma by using its significant resources and will ultimately
experience a beneficial change in its identity.
PMID- 11004768
TI - A sociohistorical view of group psychotherapy in the United States: the ideology
of individualism and self-liberation.
AB - A deep strain of individualism permeates American culture, rooted in the
political-economic ideology of capitalism. The ideal of a self-governing
individual is promoted, independent from social, historical, and cultural forces,
whose thoughts and emotions are located within the construct of a masterful self,
ready to be filled and expanded. This article traces the influence of self
liberatory ideology in American group psychotherapy through the religious
revivalist and Mental Hygiene movements. The "progressivism" of pioneering group
theorists is examined in terms of revisionist psychology and self-liberatory
practice. Psychodrama and T-groups are demonstrated to be precursors to the
encounter group movement in which the belief in self-liberation reached its
zenith. Early group analytic approaches are seen to eschew transpersonal and
group dynamic processes.
PMID- 11004769
TI - The future of the group.
AB - Group oppositional and destructive processes have been insufficiently understood
and integrated into the fabric of group psychotherapy. To strengthen our field
for the future, this area requires further elucidation. The author's concept of
the Anti-Group is used as a basis for exploring antagonistic group processes in
the clinical setting in parallel to group disruption and threat in the social
domain. Further, it is suggested that the legacy of our training organizations is
tied to problematic and institutional group processes that tend to be repeated
rather than acknowledged and resolved. These gaps in our understanding limit the
power of the group because creativity and growth come from the recognition and
transformation of destructive impulses.
PMID- 11004770
TI - Community meeting: review, update, and synthesis.
AB - The community meeting is a frequent regular meeting in a psychiatric ward or
institution that is attended by all staff and patients. It meets for the purpose
of communication, ward management, or psychiatric treatment. The conditions of
the current hospital psychiatric treatment environment are very different from
the treatment environment where the therapeutic community concept was first
established, particularly in terms of the shortened length of hospital stay and
the emphasis on pharmacologic rather than psychotherapeutic methods of treatment.
However, even with these changes, an admixture of psychopharmacologic treatment
and therapeutic community principles has been advocated as an effective,
realistic, and desirable treatment modality in today's hospital environment. A
synthesis of an extensive literature review from both a theoretical and research
perspective on the community meeting is presented. A schema has been developed
listing elements for practice in today's hospital climate.
PMID- 11004771
TI - An integrated model of group treatment for cancer patients.
AB - Considerable evidence suggests that group interventions are a valuable resource
for cancer patients, but few conceptual frameworks are available to guide
decisions about which approaches might be most useful for which patients at what
phases of illness. This article presents an integrative treatment model for group
services. It describes different group interventions geared toward patients at
different phases of illness to accommodate the shifting needs and concerns that
evolve over the course of the disease. Recommendations are offered concerning
further research and model development.
PMID- 11004772
TI - Further comments on understanding group psychotherapy by Irvin Yalom.
PMID- 11004773
TI - Growth through shame and humiliation.
PMID- 11004774
TI - Feasibility of controlling Ixodes scapularis ticks (Acari: Ixodidae), the vector
of Lyme disease, by parasitoid augmentation.
AB - A theoretical analysis of the feasibility of controlling tick populations
(Ixodidae) by the release of reared Ixodiphagus parasitoids in tick ecosystems
yielded promising results. The analysis suggested that if reasonable progress
could be made in mass-rearing the parasitoids, it would be possible to control
the blacklegged tick, Ixodes scapularis (Say), the vector of Lyme disease, by
this biological control procedure. Lyme disease has become the most important
vector-borne disease in the United States. In a field-release experiment
conducted in Africa by members of the International Center for Insect Physiology
and Ecology, effective control of Amblyomma variegatum (F.) was obtained by the
release of Ixodiphagus parasitoids in tick habitats. Encouraging theoretical
results along with the encouraging results of a field-release experiment indicate
the need for civil and political leaders in countries where ticks are a major
problem to sponsor strong and well-coordinated research initiatives focused on
the development of this new method of dealing with tick problems.
PMID- 11004775
TI - Coadaptation of male aedeagal filaments and female spermathecal ducts of the old
world phlebotomine sand flies (Diptera: Psychodidae).
AB - The morphology of insect genitalia is often highly species-specific, and its
variation has been suggested as an important impetus for evolution. Structural
variation of the male genitalia and the female spermathecae in Phlebotomine sand
flies is unique among the blood sucking Diptera. We describe the fine structures
involved in mating for Phlebotomus papatasi (Scopoli). Relationships among the
length of the spermathecal duct and aedeagal filament were studied in 26 species
of Old World phelebotomine sand flies comprising 12 subgenera. In most taxa the
aedeagal filaments were very long allowing direct insemination into the
spermathecae, indicating that intrasexual competition among males occurs as sperm
precedence. There was a positive correlation between the lengths of the
spermathecal ducts and aedeagal filaments, indicating that an evolutionary "arms
race" occurs between males and females over the control of fertilization. The
pattern of genitalia variation in phlebotomine sand flies also indicated that
differences in the lengths of the spermathecal ducts and aedeagal filaments are
distributed unevenly among closely related species. Genital differences do not
seem to occur in populations of the Phlebotomus argentipes Annandale & Brunetti
complex, whereas differences showed strongly in closely related Phlebotomus
papatasi and P. bergeroti Parrot, and in sympatric Phlebotomus martini Parrot and
P. celiae Minter.
PMID- 11004776
TI - Vector competence of Aedes aegypti, Culex sitiens, Culex annulirostris, and Culex
quinquefasciatus (Diptera: Culicidae) for Barmah Forest virus.
AB - Aedes aegypti (L.), Culex sitiens Weidemann, Culex annulirostris Skuse, and Culex
quinquefasciatus Say mosquitoes colonized at the Queensland Institute of Medical
Research, Brisbane Australia, were fed on blood containing Barmah Forest virus
(BF). Only Cx. annulirostris was susceptible to infection, with a median cell
culture infectious dose (CCID50) of 10(3.36) per mosquito. Ae. aegypti and Cx.
quinquefasciatus were infected experimentally, but at rates of < 9%. Cx. sitiens
did not become infected. Infection rates for Cx. annulirostris fed 10(3.5) CCID50
of virus per mosquito, varied from 9 to 50% between 2 and 13 d after infection.
Virus transmission to suckling mice by Cx. annulirostris occurred from 2 d after
infection. Transmission of BF virus by Cx. annulirostris was 10% at 2 d after
infection and did not exceed 8% thereafter. Although Cx. annulirostris may be
infected and is able to transmit BF virus to suckling mice, it is nonetheless a
relatively inefficient vector of the virus.
PMID- 11004777
TI - Early warning of malaria epidemics in African highlands using Anopheles (Diptera:
Culicidae) indoor resting density.
AB - Several highland regions of Africa recently have suffered malaria epidemics.
Because malaria transmission is unstable and the population has little or no
immunity, these highlands are prone to explosive outbreaks when densities of
Anopheles exceed critical levels and conditions favor transmission. If an
incipient epidemic can be detected early enough, control efforts may reduce
morbidity, mortality, and transmission. Here we present three methods (direct,
minimum sample size, and sequential sampling approaches) that could be used to
determine whether the household indoor resting density of Anopheles gambiae s.I.
has exceeded critical levels associated with epidemic transmission. Data on
Anopheles density before, during, and after a malaria epidemic (December 1997
July 1998) in the highlands of southwestern Uganda were evaluated to demonstrate
the application of these three approaches. During this epidemic, a density of
0.25 Anopheles mosquitoes per house was associated with epidemic transmission,
whereas 0.05 mosquitoes per house was chosen as a normal level expected during
nonepidemic months. The direct approach to calculating mean Anopheles density
with an allowable error of 20-50% of the mean would require the sampling of 102
16 houses, respectively. In contrast, with only seven houses, the minimum sample
size approach could be used to determine whether Anopheles density had exceeded
the critical level. This method, however, would result in an overestimation of
the risk of an epidemic at low Anopheles density. Finally, a sequential sampling
plan could require as many as 50 houses to conclude that risk of an epidemic
existed, but this disadvantage is offset by the ability to preset the
probabilities of concluding that risk of an epidemic exists at both the critical
and normal Anopheles densities. Our study illustrated that it is feasible, and
probably expedient, to include monitoring of Anopheles density in highland
malaria epidemic early warning systems.
PMID- 11004778
TI - Seasonal abundance and survivorship of Culicoides sonorensis (Diptera:
Ceratopogonidae) at a southern California dairy, with reference to potential
bluetongue virus transmission and persistence.
AB - Seasonal abundance and survivorship of Culicoides sonorensis Wirth & Jones were
examined at a dairy in southern California from January 1995 to December 1997.
Insects were collected one to two times per week using five CDC-type suction
traps (without light) baited with CO2 at a constant release rate of 1,000 ml/min.
Female and male abundance was greatest during late summer and early fall and was
directly correlated with mean monthly air temperature. Parity of females was
lowest during late summer and early fall. The gonotrophic cycle was estimated to
require 3-4 during hot summer months and up to 14 d during cool winter months.
Estimated extrinsic incubation of bluetongue virus (BLU) was 9-10 d during August
and September. The estimated daily survival ranged from < 60% in the summer to >
95% in the winter, resulting in an expectation of life of only 2-3 d in summer
and > 10 d in winter. The probability of females surviving the extrinsic
incubation period for BLU virus, and the expectation of infective life were both
lowest during late summer and early fall. During 1997, midge abundance during
late summer was not high enough to overcome very low survivorship, and the
absolute number of females expected to survive the extrinsic incubation period
was relatively low. However, in 1995 and 1996, very high midge abundance
compensated for low survivorship during summer and the number of females expected
to survive the extrinsic incubation period was relatively high. Although
abundance was generally very low during the cool winter and spring, host-seeking
females were captured throughout the year, and their winter survival was high.
Overwintering of BLU virus by continued transmission of the virus by active
midges appears possible.
PMID- 11004779
TI - Effects of temperature and pH on hexokinase from the flight muscles of
Dipetalogaster maximus (Hemiptera: Reduviidae).
AB - Effects of temperature and pH on the catalytic properties of hexokinase (HK, EC
2.7.1.1) from the flight muscles of Dipetalogaster maximus (Uhler) were studied.
The enzyme showed a hyperbolic behavior with its two substrates (glucose and
ATP). There was no inhibition by glucose. Apparent Km and Vmax increased as pH
increased from 7.0 to 8.5. Catalytic efficiency was lowest at pH 7.0. Km, Vmax,
and catalytic efficiency were higher at 37 degrees C than at 30 and 20 degrees C.
There was marked inhibition by ATP, which was dependent on pH and temperature. Km
values for ATP were reduced and catalytic efficiency increased as pH increased.
Lowest Vmax was observed at pH 7.0. At this pH there was 87.3% inhibition by ATP,
whereas it was only 5.7% at pH 8.5 (at 30 degrees C). Km, Vmax, and catalytic
efficiency were higher at 37 degrees C than at 30 and 20 degrees C. The strong
inhibition by ATP detected at 20 degrees C (pH 7.6) almost disappeared at 37
degrees C. Therefore, temperature could regulate hexokinase activity by
modulating the inhibition produced by ATP. Glucose utilization and ATP production
would be promoted when temperature rises from 30 to 37 degrees C. Because insect
thoracic muscles increase their temperature over 30 degrees C during flight, this
phenomenon elucidates a mechanism enhancing energy supply for muscle activity.
PMID- 11004780
TI - Density and distribution of Dirofilaria immitis (Nematoda: Filarioidea) third
stage larvae in Aedes sollicitans and Aedes taeniorhynchus (Diptera: Culicidae).
AB - Numbers and the distribution of third-stage larvae (L3) were investigated in
Aedes sollicitans (Walker) and Aedes taeniorhynchus (Wiedemann) female mosquitoes
fed Dirofilaria immitis (Leidy) infectious-blood with densities of microfilariae
(mf) ranging from approximately 7,100-43,400 mf/ml. At each microfilarial
density, a maximum of 63-66 infective larvae were recovered from an Ae.
sollicitans alive on day 15 after infection. In comparison with Ae.
taeniorhynchus, Ae. sollicitans averaged greater numbers of L3 and from 1.4 to
2.4 times more L3 in the head and labium per infected female. The trend was for
greater numbers of L3 to be found in the labium than in the head of Ae.
sollicitans, but there were no significant differences between numbers of L3
recovered from these sites in differentially infected females. However, numbers
of L3 recovered from the head versus the labium of differentially infected Ae.
taeniorhynchus varied significantly with the infectious blood microfilarial
density. At the two lowest and highest microfilarial densities, greater numbers
of L3 were recovered from the head and labium, respectively. Variations among
species in the female body size, blood meal size, and retention of L3 may be
factors responsible for differences observed between the total numbers and
percentage distribution of D. immitis L3 recovered from the simultaneous blood
fed Ae. sollicitans and Ae. taeniorhynchus.
PMID- 11004781
TI - Effect of eastern equine encephalomyelitis virus on the survival of Aedes
albopictus, Anopheles quadrimaculatus, and Coquillettidia perturbans (Diptera:
Culicidae).
AB - The effect of eastern equine encephalomyelitis (EEE) virus on the survivorship of
Aedes albopictus (Skuse), Anopheles quadrimaculatus Say, and Coquillettidia
perturbans (Walker) was determined experimentally. Female mosquitoes were allowed
to feed on EEE viremic chicks, and survival rates were compared for infected and
uninfected mosquitoes. Additionally, the survival of female Cq. perturbans and
An. quadrimaculatus intrathoracically (i.t.) inoculated with EEE was compared
with controls receiving diluent inoculations. Infection with EEE significantly
reduced survival in Cq. perturbans compared with uninfected individuals in per os
infection experiments. I.t. infections of Cq. perturbans did not reduce survival
when compared with diluent inoculated groups. In contrast, infection with EEE did
not affect the survival of Ae. albopictus after per os infection or An.
quadrimaculatus after either i.t. or per os infections.
PMID- 11004782
TI - Characterization of a new spotted fever group rickettsia detected in Ixodes
ricinus (Acari: Ixodidae) collected in Slovakia.
AB - Two previously undescribed rickettsiae were detected in Ixodes ricinus Ricketts
by polymerase chain reaction. Ixodes ricinus Slovakia (IRS) 3 and IRS4 were
identified in ticks collected in northeastern and southwestern Slovakia,
respectively. Sequences of the 16S rRNA citrate synthase (gltA) and outer
membrane protein rOmpA (ompA) encoding genes of both strains were nearly
identical but were distinct from those of all other known rickettsiae.
Phylogenetic relationships inferred from the comparison of these sequences with
those of other members of the genus Rickettsia indicate that IRS3 and IRS4
constitute a new rickettsial genotype and form a separate cluster among the
spotted fever group rickettsiae.
PMID- 11004783
TI - Life cycle of Ixodes (Ixodes) loricatus (Acari: Ixodidae) under laboratory
conditions.
AB - The life cycle of Ixodes (Ixodes) loricatus Neumann, reared in the laboratory, is
described. Engorged females collected from opossums trapped in the states of
Minas Gerais and Sao Paulo, Brazil, which were used to start the laboratory
colonies, were designated as BMG and CSP, respectively. Larval and nymphal ticks
from both colonies fed separately on Rattus norvergicus Berkenhout or Calomys
callosus Rengger, whereas Didelphis marsupialis L and Didelphis albiventris Lund
were used as hosts for BMG and CSP adults, respectively. Biological and
developmental data obtained from ticks of both the BMG and CSP colonies that were
reared separately for two consecutive generations were compared. The percentage
of fed or molted ticks reared on C. callosus was higher than that recorded for
ticks fed on R. norvergicus in the majority of the observations. Despite
significant differences among several of the biological parameters, the pattern
of the life cycles of the two tick colonies was similar. Results indicated that
the mean life cycle duration of I. (I.) loricatus was approximately 7 mo from
parental oviposition to the occurrence of F1 eggs, regardless of geographic
origin or host species.
PMID- 11004784
TI - Resistance to insecticides and effect of synergists on permethrin toxicity in
Pediculus capitis (Anoplura: Pediculidae) from Buenos Aires.
AB - Permethrin-resistant colonies of Pediculus capitis (De Geer) from Buenos Aires
were used to establish a resistance profile and to examine resistance mechanisms.
All permethrin-resistant head lice (resistance ratio from 52.8 to > 88.7) were
also resistant to d-phenothrin (resistance ratio from 40.86 to > 48.39) and
deltamethrin (resistance ratio from 16.24 to 38.06). No cross-resistance to
carbaryl was found in any of the pyrethroid-resistant P. capitis tested.
Otherwise, all resistant colonies showed low to high levels of resistance to beta
cypermethrin. This pyrethroid had never been applied as a pediculicide in
Argentina; however, the high level of resistance found in these permethrin
resistant colonies (resistance ratio from 9.74 to 50.97) demonstrated that
pyrethroid cross-resistance occurred to this novel insecticide. Treatment with
piperonyl butoxide (PBO) or triphenylphosphate (TPP) significantly decreased the
toxicity of permethrin in the four colonies tested. The esterase inhibitor TPP
produced lower enhancement of toxicity than the multifunction oxidase inhibitor
PBO in the colonies having the highest resistance levels. Results presented here
concerning the cross-resistance profile and synergism by enzyme inhibitors in
permethrin-resistant head lice demonstrated that enhanced metabolism was involved
in the pyrethroid resistance. However, the substantial degree of resistance that
remained after synergism suggested the presence of another resistance mechanism.
Cross-resistance to pyrethroid and susceptibility to the carbamate carbaryl
suggested a common action mechanism.
PMID- 11004785
TI - Lipid utilization for ovarian development in an autogenous mosquito, Culex
pipiens molestus (Diptera: Culicidae).
AB - During the first ovarian cycle, autogenous female mosquitoes develop their
ovaries in the absence of blood feeding. In autogenous Culex pipiens molestus
(Forskal), complete yolk deposition was observed 2 d after emergence, even when
no feeding was allowed (starved). Neutral lipids in Cx. p. molestus increased
during the pupal stage, abruptly declined after emergence, and again increased on
day 3. In contrast, neutral lipids decreased in anautogenous Anopheles stephensi
(Liston) and Cx. p. pallens (Coquillett) and starved females died within 2-3 d
after emergence. High ratios of two major neutral lipids, free fatty acid and
triglyceride, were isolated by thin-layer chromatography (TLC) from the lipid
contents of both Cx. p. molestus and An. stephensi fourth-instars and newly
emerged females. Fatty acid analyses using gas liquid chromatography (GLC) and
GLC-mass spectrometry (GLC-MS) showed higher proportions of unsaturated than
saturated fatty acids in Cx. p. molestus at both stages and two major neutral
lipids: free fatty acids and triglycerides. The percentage composition of
linoleic acid (C18:2), which is a precursor of arachidonic acid, was higher in
Cx. p. molestus than in An. stephensi. Our results indicated that elevated lipid
content before emergence may play a role of inducing ovarian development in
autogenous mosquitoes.
PMID- 11004786
TI - Effects of density and larval competition on selected life history traits of
Culex pipiens quinquefasciatus (Diptera: Culicidae).
AB - The effects of larval densities of one to four individuals in standard Drosophila
vials (diameter 25 by 95 mm) on the age at pupation, starved dry weight, and wing
length of Culex pipiens quinquefasciatus Say were studied. This approach required
relatively few larvae per replicate and included a control treatment, where
individual larvae developed in the absence of competition. This design also
tested for competitive interactions between male and female larvae. Mosquitoes
pupated later, and emerged with lighter starved dry adult weight and shorter
wings as larval density increased. The size of adult female mosquitoes,
particularly their starved dry weight, was sensitive to larval density and also
was influenced by the presence or absence of competition with another female
larva. In contrast, the life history traits of males did not vary as a function
of competition with female larva. Female larvae were also more likely to die in
the highest density treatment. This design confirmed previous results and offered
a potentially useful experimental approach to investigate the effects of density
dependent competition among mosquito larvae.
PMID- 11004787
TI - Definition of species in the Culex sitiens subgroup (Diptera: Culicidae) from
Papua New Guinea and Australia.
AB - Japanese encephalitis is a disease of major importance in Asia, which from 1995
has extended its range into the north of Australia. Culex annulirostris Skuse of
the Culex sitiens subgroup of Culex was incriminated as the most likely mosquito
vector. Because misidentifications previously have occurred within this subgroup,
our paper defines electrophoretic methods to identify Culex specimens from
Queensland and the Northern Territory in Australia and from Western Province in
Papua New Guinea. In collections from 1996 to 1998 Culex sitiens Wiedemann, Cx.
palpalis Taylor, and Cx. annulirostris comprised 93.1% of the total banded
proboscis Culex mosquitoes collected; 6.9% remained unidentified to species by
morphological or electrophoretic examination. The prevalence of Cx. palpalis was
variable and appeared to be associated with below average rainfall during 1997.
In Papua New Guinea, this species comprised up to 97.4% of banded proboscis
Culex, with smaller numbers collected from the Torres Strait Islands and Cape
York; none was collected from other Queensland localities. Cx. annulirostris was
more prevalent during years of average or above average rainfall and was
predominant in most localities, especially in the Torres Strait and Queensland.
These data confirmed the problems in separating Cx. sitiens from Cx. palpalis and
Cx. annulirostris using morphological characters.
PMID- 11004788
TI - Simulium vittatum (Diptera: Simuliidae) and Lutzomyia longipalpis (Diptera:
Psychodidae) salivary gland hyaluronidase activity.
AB - Hyaluronidase activity in the salivary gland homogenates of Simulium vittatum
(Zetterstedt) is described, and its optimal pH determined. Salivary activity was
reduced significantly after a blood meal, indicating that it was secreted after
blood feeding. Phlebotomus papatasi (Scopoli) also exhibited salivary
hyaluronidase activity. These results indicate that hematophagous pool-feeding
insects may secrete this enzyme to help the spread of salivary antihemostatic
agents in the vicinity of the feeding lesion, and perhaps to increase the size of
the feeding lesion itself. Additionally, this enzyme may affect local host immune
reactions and promote arboviral transmission.
PMID- 11004789
TI - Comparative study of the mouthparts of males and females of Lutzomyia migonei
(Diptera: Psychodidae) by scanning electron microscopy.
AB - The mouthparts of both males and females of Lutzomyia migonei Franca were
compared by scanning electron microscopy (SEM) and light microscopy (LM), and
their structures are herein described. Mandibles are present in both sexes but in
males they are reduced and, in contrast to females, no teeth were observed. As in
females, the laciniae in males are highly sclerotized, but the number of lateral
teeth are reduced and retrorse teeth are absent. Only females possess teeth at
the tip of the hypopharynx, whereas in males they are substituted by spicula.
Except for the length from the junction with the hypopharynx to the tip, which is
shorter in males than in females, the labrum is similar in both sexes in terms of
form and sensilla. On the labrum of males sensilla could be detected similar to
the apical sensilla of females which play a role in the identification of blood.
PMID- 11004790
TI - Effects of local geographic barriers and latitude on population structure in
Anopheles punctipennis (Diptera: Culicidae).
AB - We sampled Anopheles punctipennis (Say) from 11 localities throughout Vermont to
examine the effects of latitude and two local geographical boundaries, Lake
Champlain and the Green Mountains, on the population genetic structure of this
species. Thirty-five mitochondrial haplotypes were detected in 104 individuals
using a variable region of the COI gene. When latitude was examined, we detected
significant structure within localities and among localities within latitudinal
regions. For geographic analysis, significant genetic structure was detected only
within localities. Estimates of gene flow across geographic regions indicate that
the Green Mountains, but not Lake Champlain, is a barrier to dispersal for this
species. We found no correlation between genetic and geographic distances for An.
punctipennis.
PMID- 11004791
TI - Production of pheromones by artificially fed males of the tick Amblyomma
maculatum (Acari: Ixodidae).
AB - Aggregation-attachment pheromones are produced only by male ticks of the genus
Amblyomma that have imbibed blood for at least 8 d from their mammalian hosts.
This report demonstrates that production and release of aggregation-attachment
pheromones by Amblyomma maculatum (Koch) males can be induced in vitro by using
nonblood media, artificially introduced through capillary tubes, into the male
ticks. The presence of these pheromones is demonstrated by using both biological
observations on bovine hosts and in vitro experimentation with petri dishes. The
attraction of unfed female ticks to the artificially fed males (using the petri
dish method) was significantly higher (P < 0.001) than the attraction of unfed
females to unfed males. Similarly, attraction and attachment were recorded on
bovine hosts. Only 62.8 +/- 17.5% of the females released attached to the bovine
host. Of these, 61.9 +/- 19.37% attached around artificially fed males that were
placed on the bovine 24 h earlier. This percentage did not differ significantly
from the 81.4 +/- 7.1% of the total that attached around males that fed naturally
for 8 d. In comparison, only 33.3 +/- 21.9% of the total number of females placed
on the host did so after being fed 1 d (control group). The possibility of using
capillary feeding as a new tool for investigating the physiology and reproductive
behavior of blood-sucking arthropods is discussed.
PMID- 11004792
TI - Vector competence of Ixodes muris (Acari: Ixodidae) for Borrelia burgdorferi.
AB - The vector competence of Ixodes muris (Bishopp & Smith) was determined for
Borrelia burgdorferi, the etiologic agent of Lyme disease. Larval I. muris were
fed on ICR outbred mice infected with the B-31 laboratory strain of B.
burgdorferi. Replete larvae, at 5 d after feeding, were assayed for infection by
culture in Barbour-Stoner-Kelly (BSK-H) media. Infection frequency in I. muris
replete larvae was 66%. Resultant nymphs were fed on naive ICR outbred mice to
determine the ability of I. muris to transmit infection. Infection frequency in
fed nymphs declined to 38% and only 1/5 mice was positive for B. burgdorferi on
ear biopsy culture. We demonstrated that I. muris is capable of acquiring and
transmitting B. burgdorferi but is a relatively poor vector compared with I.
scapularis (Say).
PMID- 11004793
TI - Spectrofluorometers are not adequate for aging Aedes and Culex (Diptera:
Culicidae) using pteridine fluorescence.
AB - Attempts were made to use pteridine fluorescence levels as a tool for aging
individual Aedes polynesiensis Marks and Culex quinquefasciatus Say mosquitoes.
Fluorescent pigments were extracted and quantified with techniques and apparatus
(i.e., a spectrofluorometer) that can be used in developing countries or in field
laboratories, and that has already given consistent results in similar studies on
other insect groups. However, for Ae. polynesiensis as well as Cx.
quinquefasciatus, individual fluorescence measurements were mostly below the
spectrofluorometer white noise level. With batches of Aedes or Culex of the same
age, significant fluorescence levels were recorded but not in relation to their
calendar ages. The low content of pteridines in mosquitoes suggests that standard
spectrofluorometry is not sufficiently sensitive for such studies.
PMID- 11004794
TI - Ticks (Acari: Ixodidae) associated with rural dogs in Uruara, eastern Amazon,
Brazil.
AB - A survey of 124 dogs for ticks was conducted from August to November 1998 in 68
small farms of Uruara municipality in Eastern Amazon-Brazil. We collected 55
ticks from 18 dogs (14.5%). Amblyomma oblongoguttatum Koch, Amblyomma ovale Koch,
and Amblyomma cajennense (F.) were found on nine, six, and one dog, respectively.
Fourteen small farms (20.5%) had at least one dog with ticks.
PMID- 11004795
TI - A case of gynandromorphism in Amblyomma oblongoguttatum (Acari: Ixodidae).
AB - During a survey conducted from August to November 1998 to ticks associated with
dogs in the rural area of Uruara, in the state of Para, Eastern Amazon region of
Brazil, we collected one gynandromorph specimen out of 18 Amblyomma
oblongoguttatum Koch specimens collected from dogs. It is a perfect bipartite
gynandromorph, reported in this species for the first time.
PMID- 11004796
TI - Vector competence of Culex pipiens molestus (Diptera: Culicidae) from Taiwan for
a sympatric strain of Japanese encephalitis virus.
AB - Laboratory strains of Culex pipiens molestus Forskal and Culex tritaeniorhynchus
Giles from northern Taiwan were compared for their susceptibility to the Sanhsia
MQ1-2 (SH) strain of Japanese encephalitis (JE) virus isolated from Taiwan. After
feeding on a sweetened blood-virus mixture, viral titers in Cx. p. molestus
during the 14-d incubation period ranged from a minimum of 2.9 log10PFU (plaque
forming units) per mosquito on day 3 after ingestion to a maximum of 4.65
log10PFU at day 8 and in Cx. tritaeniorhynchus from 2.6 on day 10-5.18 log10PFU
per mosquito on day 13. Although virus titer in Cx. p. molestus was lower than in
Cx. tritaeniorhynchus at the end of the experiment, this difference was not
statistically significant. The median infective dose (ID50) for Cx. p. molestus
was 2.83 log10PFU and for Cx. tritaeniorhynchus was 1.02 log10PFU per mosquito,
and this difference also was not significant. There also was no significant
difference between the median infective dose for transmission (TID50) per
mosquito for Cx. p. molestus (5.34 log10PFU) and Cx. tritaeniorhynchus (4.59
log10PFU). We concluded that Cx. p. molestus is an effective laboratory vector of
JE virus.
PMID- 11004797
TI - Oral infection of Culicoides sonorensis (Diptera: Ceratopogonidae) by vesicular
stomatitis virus.
AB - Vesicular stomatitis virus serotype New Jersey (VSNJV) was mixed with bovine
blood or fetal bovine serum (FBS) and fed across silicone membranes to laboratory
populations of Culicoides sonorensis Wirth & Jones. In an initial study, virus
was detected after 13 d in 21% of the midges that received an FBS/VSNJV mixture.
In subsequent time-course experiments, engorged females were collected and
maintained at 20.0 degrees C and assayed for VSNJV immediately after feeding and
at 1, 3, 7, 10 and 13 d after feeding. Virus was detected after 13 d in 3% of the
midges that received a bovine blood/VSNJV mixture and in 9% of the midges that
received an FBS/VSNJV mixture. The results indicate that C. sonorensis should be
considered as a potential biological vector of VSNJV.
PMID- 11004798
TI - [Two-step tuberculin skin testing in our hospital employees].
AB - To evaluate the baseline values of tuberculin reaction, two-step tuberculin skin
testing was carried out in 365 employees of our hospital. We defined strongly
response group when the size of erythema showed more than 30 mm or who showed
strongly positive reaction. Two-step tuberculin skin testing was carried out in
165 hospital employees excluding those who were defined as the strongly response
group in the first testing. 80 hospital employees (48.5%) became strongly
response group by the second tuberculin skin testing. Altogether, 76.7% of all
employees were strongly response group either by the first time or the second
tuberculin skin testing. The size of erythema and that of induration showed 13.2
+/- 12.6 mm (mean +/- SD), 6.9 +/- 9.2 mm increase, respectively, in the two-step
tuberculin skin testing, so-called Booster phenomenon. We could not know the true
tuberculin reaction status by the single tuberculin skin testing. Therefore, two
step tuberculin skin testing is important as one of an infection prevention
countermeasures in the hospital workers.
PMID- 11004799
TI - [Transitional pattern of the clinical features of patients with pulmonary
tuberculosis in a community hospital].
AB - To determine changes in the clinical features of recent patients with pulmonary
tuberculosis in a community hospital without restricted tuberculosis wards, the
clinical findings of 112 patients with pulmonary tuberculosis (containing miliary
tuberculosis) during the past 15 years were compared by dividing the patients
into three groups, each encompassing a five-year period. Recently, the number of
patients with pulmonary tuberculosis was found to be increasing in a community
hospital. In particular, the percentages of elderly patients and smear positive
patients have increased. However, because of the improving awareness on
tuberculosis, we have diagnosed TB cases correctly on admission and tended to
perform the appropriate treatment. The comparative study between pulmonary
tuberculosis patients diagnosed at the outpatients department and diagnosed after
admission indicated that the patients diagnosed after admission showed pneumonia
like infiltrative shadows without cavity formation and lower smear positivity for
tubercle. Fortunately, resistance to antituberculous drugs of isolated tubercle
bacilli in our community hospital has not yet increased and the prognosis of the
cases proved to be good when the appropriate treatment was performed at an early
stage.
PMID- 11004800
TI - [Management of pulmonary tuberculosis patients complicated with diabetes mellitus
before diagnosis as pulmonary tuberculosis and feasibility of chemoprophylaxis].
AB - We studied whether diabetics who are one of the high risk groups of developing
pulmonary tuberculosis had undergone chest X-ray examination periodically. The
feasibility of chemoprophylaxis in diabetics was also studied by investigating
whether fibrotic lesions of tuberculosis can be found on previous chest X-ray
films of these patients. Of the pulmonary tuberculosis patients admitted to our
hospital for treatment, 78 patients complicated with diabetes mellitus were
enrolled in this study. As to the mode of detection, the majority, 63 cases, are
discovered, by undergoing medical examination because of respiratory symptoms,
followed by 8 patients in whom pulmonary tuberculosis was found by health
examination and only 1 patient was found by the periodic observation of diabetes
mellitus. Of the 57 patients receiving the original treatment for pulmonary
tuberculosis preceded by the discovery of diabetes mellitus, only 15 (26%) had
undergone chest X-ray examination periodically. This fact shows that physicians
treating diabetes mellitus have only a little concern on tuberculosis, thus the
re-training of physicians dealing with diabetics on tuberculosis is considered to
be necessary. According to chest X-ray films of 21 patients who had undergone
chest X-ray examination and in whom the previous films were available, there were
6 patients without any lesion of pulmonary tuberculosis, 8 patients with fibrotic
lesions and 7 patients with active lesions. The 8 patients showing fibrotic
lesions have developed pulmonary tuberculosis on the average 15 years after they
were diagnosed with diabetes mellitus, and the fact suggests that the prevention
of the development of pulmonary tuberculosis among diabetics could be possible by
chemoprophylaxis.
PMID- 11004801
TI - [Study of the two-step tuberculin tests and gamma-interferon assays in elderly
persons].
AB - Recently, an outbreak of lung tuberculosis among elderly residents happened in
the home for aged, and it has become a social problem. To analyze the problem of
tuberculosis in the elderly persons, we performed two-step tuberculin tests at
two weeks interval and gamma-interferon assays for diagnosis of human
tuberculosis to residents in the home for aged. 45 males (age; 77.3 +/- 8.9 SD)
and 118 females (age; 81.9 +/- 8.6 SD) elderly persons (> or = 60) were examined.
Standard dose of PPD was injected intracutaneously, and read at 48 hours.
Erythema of 10 mm diameter or more was considered positive. The results were as
follows. (1) The percentages of positive reactors in the 1st (T1) and the 2nd
(T2) tuberculin tests were 50.3% and 68.1%, respectively. (2) The diameters of
erythema and percentage of positive reactors (T1) did not very with age, but the
size of erythema increased from 13.5 mm (T1) to 21.2 mm (T2) among those below 80
years, and from 13.0 mm (T1) to 16.4 mm (T2) among those 80 years or higher (p <
0.01). (3) The percentage of positive reactors (T1) varied by sex, namely males
react stronger than females. (4) A dose of interferon-gamma released specifically
in response to PPD stimulation of whole blood cultures showed no close relation
with the diameters of erythema. In conclusion, tuberculin reactivity waned among
elderly persons, and the fact suggests that they would have lower resistance
against new infections, and as a result, they might have higher risk of
developing tuberculosis. Elderly residents should be performed two-step
tuberculin tests at the time of their entrance to the home for aged, and negative
reactors should carefully be followed up.
PMID- 11004802
TI - [Study on recombinant BCG].
AB - The progress of study on recombinant BCG was stated briefly. And then our studies
on recombinant BCG were mentioned. Recombinant BCG secreting alpha antigen-fused
merozoite surface protein 1 (MSP 1) was prepared and tested for its ability to
control infections of Plasmodium yoelii. Result turned out it controlled the
infection better than recombinant MSP 1 mixed with Freund incomplete adjuvant
did. Recombinant BCG secreting excess amounts of antigen 85 complex A controlled
infection of Mycobacterium leprae. Addition of recombinant BCG secreting alpha
antigen-fused IL-2 to peritoneal exudate cells induced IFN-gamma resulting in
killing bladder cancer cells more efficiently than parental BCG did.
PMID- 11004803
TI - [Pathophysiology of reflux esophagitis].
AB - Reflux esophagitis is more frequent in developed countries, and its prevalence
increased in Japan in these 1/4 centuries. These increase might be based on the
increase in the population of the elderly, advances in endoscopic technology,
increase in the interest on esophagitis, and declined prevalence of Helicobacter
pylori infection. Main pathogenesis on the reflux esophagitis are classified as 2
components. One is the motility factor of the stomach and the esophagus.
Distention of the stomach causes transient LES relaxation(TLESR), leading acid
reflux into the esophagus. Delayed gastric emptying enhances gastric distention,
causing TLESR. Resting LES pressure might be lower than normal. Hiatal hernia is
also an exaggerating factor, causing repeated reflux from the hernia sac. The
other main cause is the intact acid secretion causing enough to injure the
esophageal mucosa. Gastric atrophy due to Helicobacter pylori infection would be
protective factor for reflux esophagitis.
PMID- 11004804
TI - [Clinical update of GERD].
AB - In our country, it is reported that reflux esophagitis(GERD) has been increasing
like in European countries. One of the reasons for this tendency may be the
arrival of the aging society. Another explanation is the lowering of Helicobacter
pylori infection rate in the younger generation. Though the Los Angeles
classification is mainly used at present, the Savary-Miller classification is
also clinically important. For the initial treatment of GERD, proton pump
inhibitor(PPI) has been mainly used, while there is large problems in the ideal
way of maintenance therapy. The guideline on the GERD treatment is also being
considered, based on EBM.
PMID- 11004805
TI - [Gastric acid secretion in gastroesophageal reflex disease].
AB - The gastric acid secretion was evaluated by serum pepsinogen I/II ratio and serum
Helicobacter pylori IgG antibody titer in gastroesophageal reflux disease(GERD)
patient. GERD patients was 81 patients. Los-Angeles classification (LA)O, so
called endoscopy negative reflux disease, was 6 patients, and LA-O-B patients was
68 patients. Helicobacter pylori infection ratio in GERD patients was 50.6%(41/81
patients). Pepsinogen I/II ratio in Helicobacter pylori positive GERD patients
was no significant different from Helicobacter pylori negative GERD patients. We
concluded that the gastric acid secretion in GERD patients was normal secretion.
PMID- 11004806
TI - [Helicobacter pylori infection and eradication].
AB - H. pylori infection is associated with various gastroduodenal diseases such as
gastritis, peptic ulcer, gastric cancer, gastric MALT lymphoma. H. pylori
infection is suggested that it plays a role as protective factor not promoting
factor for reflux esophagitis and GERD. Epidemiological studies showed lower
prevalence of H. pylori infection in reflux esophagitis and Barrett's esophagus
comparing the control. Increased occurrence of reflux esophagitis after curing of
H. pylori infection was reported. However, the relationship between H. pylori
infection and reflux esophagitis has not been actually made clear. Also the
mechanism of reflux esophagitis occurrence after H. pylori eradication is not
obscure.
PMID- 11004807
TI - [Endoscopic classification of reflux esophagitis].
AB - A new endoscopic classification of reflux esophagitis was proposed in Los Angeles
in 1994(LA classification). A mucosal break was defined as 'an area of slough or
an area of erythema with a discrete lined demarcation from the adjacent or normal
looking mucosa'. Reflux esophagitis is divided into four grades according to the
severity of its mucosal break. We can find a minimal change during endoscopy
which is not a mucosal break but is histologically or chromographically reflux
esophagitis. I think Los Angeles classification must include the minimal change
and I propose a modification of LA classification which includes the minimal
change as grade M and the esophagus without any minimal change and mucosal break
as grade N.
PMID- 11004808
TI - [Histopathological diagnosis in reflux esophagitis].
AB - We reviewed the histopathological features for the diagnosis of reflux
esophagitis and gastroesophageal reflux disease(GERD) including carcinogenesis of
the esophagus. Histologically, the presence of capillary dilatation, elongation
of papillary, hyperplasia of basal layer, inflammatory cells-infiltration,
balloon cells in the epithelium, and ulceration were evaluated in GERD cases.
Although, histopathological changes were not clear in endoscopic-negative GERD
cases, immunohistochemical examination with cell cycle protein(PCNA, p21, and
p27) revealed the same abnormalities with GERD cases. In Japan, the majority
cases of GERD are evaluated in grade according to Los Angeles system, therefore
the prevalence of Barrett's esophagus and cancer is very low. We hypothesize that
esophageal squamous cell carcinoma arising from GERD different from Barrett's
cancer sequence, and clinicopathological long-term follow up will be required to
assess the carcinogenesis including gene analysis.
PMID- 11004809
TI - [Clinical significance of 24-hour intraesophageal pH monitoring in GERD
patients].
AB - 24-hour intraesophageal pH monitoring(24-pH-M) is a method of choice to measure
the esophageal acid exposure, and evaluate a patient's lifestyle who has reflux
symptoms. The 24-pH-M is indicated to the cases who have at least one of the
following signs/symptoms; endoscopy negative GERD(gastroesophageal reflux
disease), atypical clinical course for reflux disease, atypical symptoms of GERD,
and those who are subjected to have surgical treatment. In the 24-pH-M, not only
the duration of gastroesophageal reflux(GER), but also reflux and symptom
association should be evaluated. The 24-pH-M is useful to investigate the
diagnosis and treatment of GERD including reflux esophagitis.
PMID- 11004810
TI - [Clinical significance of ambulatory intraesophageal bilirubin monitoring in
diagnosis of gastroesophageal reflux].
AB - To evaluate the usefulness of ambulatory intraesophageal bilirubin monitoring in
the diagnosis of GER, 38 patients with reflux symptoms and 7 controls were
studied, using Bilitec 2000. The % time of bilirubin and acid reflux was less
than 5% in all of the controls. In 3 patients of NUD, % time of acid reflux was
less than 5%, but that of bilirubin was more than 8% in 2 patients. Acid reflux
was found only in 1 of 4 patients who had a history of subtotal gastrectomy, but
abnormal bilirubin reflux was found in all of 4 patients. In the other 31
patients, a significant difference was found in the % time of bilirubin reflux by
the severity of reflux esophagitis, whereas this difference was not found in that
of acid reflux. Intraesophageal bilirubin monitoring is useful in the diagnosis
of GER and is essential in patients with hypochlorhydria or minimal reflux.
PMID- 11004811
TI - [Esophageal peristalsis, lower esophageal function, and the methods of their
evaluation].
AB - Esophageal peristalsis and lower esophageal sphincter(LES) function have an
influence on gastroesophageal reflux disease(GERD). Incomplete contraction during
primary and secondary peristalsis leads to poor clearance of refluxed gastric
acid. Failure of LES function can result in a low basal LES pressure, absent or
incomplete LES relaxation after swallowing, or an inadequate increase of LES
pressure accompanying gastric activity. In addition, transient LES
relaxation(TLESR) has been suggested as an important factor in GERD. Recent
studies have indicated that TLESR has a relationship to nitric oxide(NO) and
cholecystokinin(CCK).
PMID- 11004812
TI - [The clinical evaluation of structured questionnaire for reflux esophagitis].
AB - Reflux esophagitis is suspected on clinical grounds and confirmed by a variety of
endoscopical, roentgenological and physiological investigations, which are
obviously inapplicable to an epidemiological survey. Questionnaire for the
diagnosis of reflux disease(QUEST) can reduce bias introduced by observer
variability, is practical, inexpensive, and noninvasive. QUEST also has good
sensitivity and specificity for reflux esophagitis, so it's one of the useful
diagnostic tools for reflux esophagitis. It, however, needs to be modified for
the diagnosis of gastroesophageal reflux disease (GERD). Questionnaires to
measure Quality of Life(QOL) quantitatively can be applied to the assessment of
the severity of diseases or drug efficacy, and they are useful especially for the
evaluation of endoscopy-negative GERD.
PMID- 11004813
TI - [Guideline for treatment of gastroesophageal reflux disease].
AB - The endpoints should be settled before the treatment of GERD. These are symptom
relief, healing and maintenance of erosive or ulcerative lesions, and also
probably prevention of several complications of GERD. In medical treatment for
GERD, we can take some different strategies, that is, single-agent, step-up or
step-down therapy. The authors reviewed the effects of many drugs, being used for
GERD therapy, and decided the levels of therapeutic effects from the view point
of EBM. Using these results, we recommended that the therapy of GERD should be
started with PPI of a regular dose and stepped-down in usual cases, but it should
be begun with PPI and stepped-up in refractory cases. PPI may be necessary also
for maintenance treatment in most latter cases. The guideline of the treatment
for GERD were discussed.
PMID- 11004814
TI - [Comparison between histamine H2-blocker and proton pump inhibitor on the effects
of initial treatment in reflux esophagitis].
AB - I have reviewed the comparison between histamine H2 blocker(H2-RA) and proton
pump inhibitor(PPI) on the effects of initial treatment in patients with reflux
esophagitis. Pathophysiology of reflux esophagitis has been thought to be
gastroesophageal reflux of the gastric acid, due to motor dysfunctions of the
esophagus and the stomach. Endoscopic healing rate of reflux esophagitis is
significantly higher 84% on PPI treatment than 52% on H2-RA treatment at 8 weeks
period. Because suppression of the gastric acid secretion is significantly
stronger and longer on PPI than H2-RA, especially this suppression is markedly
found in day time and also night time. On the initial treatment of reflux
esophagitis, PPI is choice so-called "step down therapy" after healing, H2-RA
and/or prokinetic drugs are treated as maintenance therapy.
PMID- 11004815
TI - [Drug therapy for nocturnal gastric acid breakthrough].
AB - Nocturnal gastric acid breakthrough(NAB) is defined as nighttime periods of over
1 hour duration, with a gastric pH < 4.0, during administration of a proton pump
inhibitor(PPI). Although the causative mechanism of NAB is unclear, this
phenomenon is a serious problem for patients with high grade reflux esophagitis.
NAB is more frequently observed in patients with reflux esophageals, since this
phenomenon is mainly observed in cases without H. pylori infection. Bedtime
administration of H2 receptor antagonist rather than additional administration of
PPI on the standard dose of PPI is effective for the control of NAB.
PMID- 11004816
TI - [Maintenance therapy of mild form of GERD by H2 receptor antagonists].
AB - Because of high relapse rate after the healing by proton pump inhibitor(PPI) or
H2 receptor antagonist(H2RA), GERD usually needs long time maintenance therapy.
PPI is superior to H2RA in the first line as well as maintenance therapy. PPI is
necessary for severe cases of GERD. However, H2RA is sufficient for milder form
of GERD patients. Among the H2RA using in Japan, nizatidine has known to
stimulate gastric emptying and elevate LES pressure. Nizatidine may be superior
to other H2RAs in the treatment of GERD. Recently, nocturnal acid breakthrough
which night time acid is secreted even PPI is administered twice daily has been
documented. H2RAs are stronger than PPI to inhibit nocturnal acid breakthrough
and may be better than night time acid reflux.
PMID- 11004818
TI - [Surgical treatment for reflux esophagitis].
AB - Recently, PPI and laparoscopic Nissen operation were introduced to clinical field
for the treatment of reflux esophagitis. The indication of surgical treatment for
reflux esophagitis is as follows: (1) patients resistant to medical treatments,
(2) free reflux patient, (3) patients with short esophagus or stenosis, (4)
patients with respiratory complications. As for surgical treatment, there are
many operative methods were reported. Recently, laparoscopic Nissen operation is
the most popular procedure, and Toupet method, Dor method, and Tokai University
method are employed for elderly patients or patients with sever esophagitis.
Collis or Deitel operation is indicated for short esophagus patients. We should
select appropriate operative method for individual patients considering about
their pathophysiological condition.
PMID- 11004817
TI - [Long-term maintenance treatment of reflux esophagitis resistant to H2-RA with
PPI (lansoprazole)].
AB - 97 patients in 49 hospitals with erosive esophagitis unhealed after at least 8
weeks treatment with H2-RA were given primary treatment with 30 mg lansoprazol
once daily. After 8 weeks of treatment with lansoprazol, 75(77%) patients were
endoscopically healed. Healed patients were then given maintenance treatment with
either 30 mg lansoprazol once daily, 15 mg lansoprazol once daily or 20 mg
famotidine twice daily for 24 weeks. 86% of patients randomized to 30 mg
lansoprazol, 70% of patients randomized to 15 mg lansoprazol were maintained in
endoscopic healing throughout 24 weeks as compared with only 12% of patients
randomized to famotidine in endoscopic healing. After 24 weeks of lansoprazol
treatment basal gastrin levels were moderately increased. However no significant
histopathologic lesion was found in the oxyntic gland mucosa. PPI(lansoprazol)
was far superior to H2-RA(famotidine) in preventing recurrence of healed erosive
esophagitis. A goal achieved without adverse events and significant abnormalities
in the oxyntic mucosal exocrine or endocrine cell but a moderate increase in
basal gastrine levels.
PMID- 11004819
TI - [Simple antireflux measures for management of gastroesophageal reflux disease].
AB - It is widely accepted that proton pump inhibitors are the most effective therapy
for management of gastroesophageal reflux disease. H2-receptor antagonists,
prokinetic agents, and antacids are used in treatment of gastroesophageal reflux
disease. In addition to these medical treatments, beneficial effects of simple
anti-reflux measures on management of gastroesophageal disease are evaluated.
Simple anti-reflux measures include elevation of the head of the bed, weight
loss, reduced food intake, and the avoidance of precipitating foods and drugs. In
this chapter, we summarized the utility of these simple anti-reflux measures for
management of gastroesophageal reflux disease.
PMID- 11004820
TI - [Cost-effectiveness of the treatment of reflux esophagitis: proton pump inhibitor
versus histamine-2-receptor antagonist].
AB - Gastroesophageal reflux disease(GERD) is a common condition and acid-suppressing
agents are the mainstays of treatment. A clinical decision analysis comparing a
proton pump inhibitor(PPI), lansoprazole and a histamine H2-receptor antagonist
(H2RA), ranitidine for the treatment of reflux esophagitis in Japan was performed
using a Markov chain approach. The PPI was consistently superior to the H2RA with
regard to both clinical effectiveness and cost-effectiveness. Prescription of
PPIs for a one-month period would further enhance the cost-effectiveness of PPI
treatment. The PPI first strategy is the preferred therapeutic approach for
medical treatment of reflux esophagitis. We also recommend that prescription of
PPIs for a one-month period be approved by the Japanese health insurance scheme.
PMID- 11004821
TI - [Epidemiology of gastro-esophageal reflux disease].
AB - Gastroesophageal reflux disease(GERD) is believed to be common and chronic
gastrointestinal disorder. Quantitative estimates of the actual prevalence of
GERD are difficult to obtain, because those who seek health care probably
represent only a tip of the iceberg of people with GERD. The prevalence of
heartburn and/or regurgitation, considered to be reasonably specific symptoms for
the diagnosis of GERD, ranged from 10% to 48% for heartburn, from 9% to 45% for
regurgitation and 21% to 59% for both/either in systematic review of GERD and
reflux esophagitis(RE). It is widely accepted that the prevalence is lower in
Asian countries, including Japan, compared with that in Western countries.
However, the prevalence of RE in Japan may be increasing. In the case of
heartburn and regurgitation in GERD and endoscopic findings in RE, different
understandings of these terms by different investigators and subjects may have
contributed to the range of results. Symptom definitions and what is understood
by them should be among the most important considerations when undertaking
population prevalence studies on reflux like symptoms, to allow comparisons to be
made between studies.
PMID- 11004822
TI - [Aging-related physical and life style changes in the patients with reflux
esophagitis].
AB - Incidence of reflux esophagitis(RE) has increased over the past 10 years in
Japan, where aging of the population is rapidly progressing. The majority(73.6%)
of the patients with RE consisted of non-elderly males having life style problems
and of elderly females suffering from posture alterations. This suggested the
importance of the disease onset among elderly female population in addition to
that of the non-elderly male population. The risk factors specific to the elderly
patients include not only persistent acid secretion and presbyesophagus, but also
complication with orthopedic regression diseases with posture changes and
osteoporosis. The association with the latter orthopedic regression diseases has
been significantly increasing and is suggested to promote development of RE.
Further increase in the prevalence of RE is foreseen in this aging-accelerating
country.
PMID- 11004823
TI - [Reflux esophagitis with hiatal sliding hernia].
AB - Hiatal sliding hernia is often found in aged patient and some of them contribute
to the development of reflux esophagitis. We described the etiology of
gastroesophageal reflux disease(GERD) briefly and mentioned the relationship
between hiatal hernia and reflux esophagitis. The old patients suffers from GERD
are accompanying hiatal hernia at the high rate. Our successful results of
laparoscopic Nissen's operation were reported shortly. Furthermore, we reviewed
the reflux esophagitis after distal gastrectomy as most important complication
after surgery. We emphasize that we should not hesitate to perform the surgical
treatment to the patients suffering from GERD with hiatal hernia or after
gastrectomy because it is safe and bring them the better Q.O.L. after treatment.
PMID- 11004824
TI - [Barrett's esophagus].
AB - The Barrett's esophagus showing columnar metaplasia upward to the esophagus from
the esophago-gastric junction is one of the final appearance of reflux
esophagitis and important as a precancerous state of esophageal adenocarcinoma.
Especially the Barrett's mucosa with intestinal metaplasia has high potential
risk for adenocarcinoma. Although the clinical definition of the esophago-gastric
junction is not easy, the criteria of the esophago-gastric junction and the
Barrett's mucosa proposed by the Japanese Society for Esophageal Diseases is
useful. The gastro-esophageal reflux is important in the development of Barrett's
mucosa not only in the classical Barrett's esophagus but also in the short
segment Barrett's.
PMID- 11004825
TI - [Collagen disease and reflux esophagitis].
AB - The incidence of reflux esophagitis in cases of collagen disease is about 10%.
However, reflux esophagitis is seen in about 50% of scleroderma cases. Moreover,
in scleroderma the severity is correlated with the time since onset of the
disease. Endoscopy is performed more often in the severe cases, and little
therapeutic effect can be expected without use of a proton pump inhibitor.
PMID- 11004826
TI - [Gastroesophageal reflux and respiratory diseases].
AB - There is a relationship between gastroesophageal reflux and respiratory diseases.
Reflux may trigger and aggravate respiratory diseases especially bronchial
asthma. Both clinical and experimental observations suggest that the pathogenic
mechanisms may be a vagal reflex and/or microaspiration of gastric acid into the
trachea. General measures to avoid reflux and proton pomp inhibitor together with
inhaled corticosteroid are the choice for treatment of asthma associated with
gastroesophageal reflux. Xanthine derivatives and beta 2 adrenergic agonist might
be withheld in these patients. A laparoscopic surgical treatment may be an option
for patients with persistent symptoms.
PMID- 11004827
TI - [Neurology].
PMID- 11004828
TI - [Eradication model employing Mongolian gerbils treated with chemical carcinogen
and infected with Helicobacter pylori--implications for human cancer prevention].
AB - To explore the 'causal link' between Helicobacter pylori(Hp) infection and
stomach carcinogenesis, we have established experimental models of stomach
carcinogenesis in Mongolian Gerbils(MGs) using the chemical carcinogen, N-methyl
N'-nitro-N-nitrosoguanidine(MNNG) and N-methyl-N-nitrosourea(MNU). The incidence
of adenocarcinoma was significantly higher in animals treated with Hp than in the
controls. Eradication of Hp was effective in reducing the incidence of
adenocarcinoma. No gastric carcinoma was found without any chemical carcinogen.
Hp infection enhances glandular stomach carcinogenesis not only of well
differentiated type but also poorly differentiated type and signet ring cell
type. Eradication of Hp, apparently a gastric promoter rather than gastric
carcinogen, may be useful as a measure for prevention of stomach cancer.
PMID- 11004830
TI - [Videofluorographic study of swallowing in patients with severe motor and
intellectual disabilities--I. Recurrent pulmonary infections].
AB - We studied swallowing movements of 8 patients with severe motor and intellectual
disabilities and recurrent pulmonary infectious diseases. All the patients were
orally fed with no problems, but had frequent episodes of pyrexia, mostly due to
pulmonary infections. Videofluorographic studies revealed severe impairments in
the transitional and pharyngeal phases. The patients aspirated liquids, most
frequently during swallowing. Prior to swallowing pooling of liquid barium was
frequently observed in the hypopharynx, and that of purees in the pharynx after
swallowing. The delay of cricopharyngeal relaxation was also frequently observed.
Based on the videofluorographic findings, we made some efforts to provide
patients with evident or latent aspiration with better management: changes in
food textures and posture during drinking and eating. These efforts significantly
reduced the frequency of pyrexic episodes. Since latent aspiration is not
uncommon among patients with severe motor and intellectual disabilities,
swallowing disturbance should be evaluated in detail by videofluorographic
examination to improve QOL.
PMID- 11004829
TI - [The protocol of clinical trial and basic experiments for esophageal cancer using
gene transduction].
AB - We examined whether antitumor effect could be produced by retrovirally expressed
interleukin-2(IL-2) gene, glanulocyte macrophage-colony stimulating factor(GM
CSF) gene, herpes simplex virus-thymidine kinase(HSV-tk) gene and p53 gene in
human esophageal cancer cells using nude mice. Loss of tumorigenicity of IL-2 or
GM-CSF producing cancer cells were observed. The antitumor effect was also
evidenced by the injection of these cells into established tumors of wild-type
cells. In suicide gene therapy on esophageal cancer, the growth suppression of
esophageal cancer cells transducing HSV-tk gene tumors in nude mice induced by
ganciclovir treatment and all the tumors disappeared. The wild-type p53
transduced tumor cells became markedly susceptible to irradiation and anticancer
agents. Administration of cisplatine noticeably suppressed the growth of p53
transduced tumors inoculated in nude mice. We established the clinical protocol
of gene therapy for esophageal cancer using wild-type p53 gene with adenovirus
vector. In this autumn we are going to start this clinical trial.
PMID- 11004831
TI - [Videofluorographic study of swallowing in patients with severe motor and
intellectual disabilities--II. Impairment of oral phase].
AB - We studied swallowing movements in 14 patients with severe motor and intellectual
disabilities and development of the impaired oral phase. The oral phase in the
patients did not develop beyond the late weaning phase. They had impairment of
the oral phase: poor or absent lip seal, infantile swallowing, slowed or stalled
bolus transit, and oral residue after swallowing. Videofluorographic studies
revealed severe impairment in the transitional and pharyngeal phases: pooling of
liquid barium in the hypopharynx prior to swallowing, the delay of
cricopharyngeal relaxation, aspirated liquids (silent aspiration 77.8%),
aspirated purees, pooling of purees in the pharynx after swallowing. After
videofluorographic studies we made some efforts to provide patients with better
management; changes in food textures and posture during drinking and eating.
These efforts eased their feeding difficulties. Videofluorographic studies could
be helpful in evaluating swallowing disturbance in the oral phase and thereby
preventing chronic aspiration, malnutrition and feeding difficulties in patients
with severe motor and intellectual disabilities.
PMID- 11004832
TI - [Functional hemispherectomy for children aged 2 years or less for the treatment
of intractable epilepsy caused by cortical dysgenesis].
AB - Thirteen children aged 2 years or less who had intractable epilepsy caused by
cortical dysgenesis underwent functional hemispherectomy. The cerebral
malformations were hemimegalencephaly in 8 cases and focal cortical dysplasia in
5 cases. Among 11 children who were followed for at least 6 months after the
operation (6 to 54 months with a median of 26 months), 5 were seizure-free, 4
achieved > 90% seizure reduction, and 2 achieved 50-90% reduction. Ventriculo
peritoneal shunt was placed in 3 children with hemimegalencephaly. After
hemispherectomy, all the children showed improvement in psychomotor development.
Development was accelerated in 3 seizure-free children. In children with cortical
dysgenesis, functional hemispherectomy may result in remarkable seizure reduction
and steady developmental progress.
PMID- 11004833
TI - [A case of subacute sclerosing panencephalitis showing various cerebral perfusion
on 99mTc-ECD SPECT].
AB - We reported serial neuroradiological findings of a 20-year-old male with subacute
sclerosing panencephalitis, who deteriorated from Jabbour stage 2 to stage 4
rapidly in spite of oral administration of inosine pranobex. At the stage 2,
brain magnetic resonance imaging (MRI), computed tomography (CT) and [99mTc]-L, L
ethyl cysteinate dimer (99mTc-ECD) single photon emission computed
tomography(SPECT) findings were normal. As the disease progressed, brain MRI and
CT revealed diffuse cerebral white matter lesions as well as cerebral atrophy.
99mTc-ECD SPECT showed serially various perfusion of cerebrum. These findings in
99mTc-ECD SPECT may reflect the acute inflammatory process and consequent
destruction of brain tissue.
PMID- 11004834
TI - [Longitudinal study of cognitive function in two patients with focal cortical
dysplasia].
AB - To clarify the relationship between epileptic attacks and cognitive dysfunction,
we examined the serial findings of 123I-IMP single photon emission computed
tomography (SPECT) in relation to the intelligence quotient (IQ), assessed by
Wechsler Intelligence Scale of Children-Revised, in two female patients with
focal cortical dysplasia (FCD) over a 10-year period. The age of patient 1 at the
initial assessment was 2 years, and the age of patient 2 was 9 months. They
developed complex partial epilepsy in infancy, and were treated with
antiepileptic drugs, which remained effective until 11 years of age, when their
epileptic attacks recurred. Patient 1, a 14-year-old girl with FCD of the left
parietal lobe suffered from dyscalculia, right-left disorientation, and finger
agnosia even when she was free of epileptic attacks. Following the recurrence of
seizures which occurred every night, she became unable to understand what was
said to her. A hypoperfusion area detected by 123I-IMP SPECT was restricted to
the left parietal lobe during the seizure-free period, but spread to the temporo
parietal lobes following the recurrence. Her verbal IQ declined from 94 (at 9
years of age) to 63 (at 11 years and 8 months). After her seizures were
controlled again (at 14 years and 4 months), the 123I-IMP SPECT findings
improved. Patient 2, a 12-year-old girl with FCD of the left frontal lobe, showed
cognitive dysfunction. Her verbal IQ declined from 91 (at 7 years and 5 months)
to 76 (at 11 years and 8 months) following a recurrence of epileptic attacks.
123I-IMP SPECT showed hypoperfusion in the left frontal lobe, where the
accumulation count ratio (left/right ratio) declined from 0.86 (at 3 years) to
0.64 (at 11 years). These findings suggest that epileptic attacks are related to
cognitive dysfunction in FCD patients. This cognitive dysfunction appears to
correlate with the appearance of hypoperfusion areas, as detected by 123I-IMP
SPECT.
PMID- 11004835
TI - [Serum anti-arrestin antibody and disease activity of multiple sclerosis--a case
report of 4-year-old child].
AB - We report a 4-year-old girl with multiple sclerosis (MS) and increased serum anti
arrestin antibody. She was admitted to our hospital because of sustained fever,
headache and anorexia. Serial magnetic resonance imaging (MRI) revealed diffuse
high intensity of cerebral white matter and basal ganglia on T2-weighted imaging.
We treated her with high-dose intravenous methylprednisolone under a diagnosis of
ADEM. She recovered without any neurological sequelae in three months and the MRI
lesion almost disappeared. However, she developed optic neuritis and two episodes
of neurologic involvement associated with multiple white matter lesions in the
next two years. She was then diagnosed as having clinically definite MS. Anti
arrestin antibody is reportedly present specifically in adult patients with MS
and uveitis. We performed an immunoblot assay using bovine retina, and our case
revealed the presence of anti-arrestin antibody. Serial examinations showed that
the serum anti-arrestin antibody titer correlated well with the disease activity.
These results indicate that anti-arrestin antibody may be a good parameter of the
disease activity of MS even in childhood.
PMID- 11004836
TI - [Two cases of auditory disturbance caused by carbamazepine].
AB - Two cases of auditory disturbance caused by carbamazepine are reported. Patient
1, a 9-year-old boy with benign Rolandic epilepsy, developed impairment of pitch
perception one day after administration of carbamazepine. Patient 2, a 33-year
old female with glossopharyngeal neuralgia, developed impairment of pitch
perception several hours after administration of carbamazepine, complaining that
the perceived sounds became lower than previously by a semitone. Her pitch
perception recovered soon after the cessation of carbamazepine. The carbamazepine
induced disturbance in pitch perception may be more frequent than we guess.
PMID- 11004837
TI - [Shuddering attacks in four children].
AB - Shuddering attacks (SA), an uncommon benign disorder occurring during infancy or
early childhood, should be distinguished from epileptic seizures. The attacks are
shivering movements occurring daily for several seconds without impairment of
consciousness. SA are regarded as an early premature manifestation of essential
tremor (ET), and the provoking mechanism is the same between them. There are case
reports of SA, but none from Japan. We studied the pathophysiology of SA in four
children aged between 8 and 14 months using a video-EEG monitoring system. In one
patient, the shuddering movements, as indicated by contaminating electromyogram
during electroencephalography, was almost as frequent as that of ET. SA decreased
in frequency or disappeared in all our patients. One of them showed immature
brain development on MRI and had relatives with epilepsy. Another showed
flattened sella turcica. Although previous reports suggest that SAs are benign
and require no investigation, children with SA could have borderline problems
related to the development of the nervous system.
PMID- 11004838
TI - [Three infants who suddenly became unwilling to stand up presumably due to acute
cerebellar ataxia].
AB - We reported here three infants aged 11 to 12 months who, according to their
parents, suddenly became unwilling to stand up. All the patients had barely
achieved the ability to stand or to walk at the time of the illness. The symptom
developed relatively acutely in the winter months from 1997 to 1998 with a
probable preceding infection. On examination, no paralysis of the lower
extremities was observed, and muscle weakness was minimal. There were neither
violent tremors, nystagmus, nor sensory disturbance. Orthopaedic disorders were
considered unlikely. Biochemical examinations of the serum were not diagnostic,
and imagings of the central nervous system were normal. Spinal tap revealed mild
cerebrospinal fluid pleocytosis in two of the patients. All the children showed
almost complete recovery without any medication during the following period of 2
days to 2 months. Although no definite signs of ataxia were recognized in the
three patients, a diagnosis of acute cerebellar ataxia was considered to be
appropriate. Mild, infantile acute cerebellar ataxia may be overlooked because of
the obscure complaints of the parents and the difficulty in performing a thorough
neurological examination of infants.
PMID- 11004839
TI - [Supplementary motor area epilepsy associated with ADHD in an abused history].
AB - A 6-year-old girl with attention-deficit hyperactivity disorder (ADHD) who had
been abused by her mother in infancy developed supplementary motor area (SMA)
epilepsy. The seizure was characterized by bilateral tonic seizure of the upper
and lower extremities, speech arrest, preserved consciousness and a lack of
postictal confusion. The duration of the seizure was usually 10-60 seconds. The
seizures sometimes clustered. She was diagnosed as having SMA epilepsy based on
the characteristic clinical symptoms, interictal EEG, ictal video-EEG and ictal
SPECT. Though her seizure was initially improved by anti-epileptic drugs, the
symptoms appeared again after discharge. Since her clinical course indicated that
her seizure was aggravated by her mental state, treatment included both
medication with anti-epileptic drugs and the adjustment of her living environment
in cooperation with a child guidance clinic. Thereafter both her epileptic
seizure and ADHD symptoms improved. These changes may be related to each other,
because both conditions are associated with frontal lobe dysfunction. It was
interesting that the adjustment of the environment improved frontal lobe
epilepsy, which in turn ameliorated ADHD symptoms.
PMID- 11004840
TI - [Historical review of pediatric brain death in Japan].
AB - Although brain death of children has recently been hotly discussed in Japan,
there still remain uncertainty and confusion. A pediatrician's diagnosis that a
child is brain-dead entails delicate and emotional issues. Circumstances of the
patients, families and institutions are so variable that many questions cannot be
answered. It is most important to be aware of these problems and to seek
consensus in the community. Pediatricians should provide their best care to both
the patients and their families.
PMID- 11004841
TI - [Brain death in pediatric patients--from the viewpoint of pediatric intensive
care].
AB - In Japan, "brain death" has been discussed exclusively in connection with organ
transplantation. However, the concept of brain death, which emerged with the
progress in intensive care medicine, should be discussed in the context of
palliative care in the ICU. It should be recognized that intensive care medicine
includes not only life-saving high-tech therapeutic modalities, but also ethical
and psycho-social aspects of modern medicine. In order to find out a decent
solution to pediatric brain death issues, it is essential to develop pediatric
intensive care in Japan.
PMID- 11004842
TI - [Role of nurses for donor's families: current issue of organ transplant in the
United States].
AB - To define the roles of donor coordinators (certified procurement transplant
coordinators; CPTCs), we visited University of Florida Colleges of Nursing and
Medicine and certified procurement transplant interviewed (CPTCs) and clinical
specialists in pediatric critical care. Recipients were dealt with certified
clinical transplant coordinators (CCTCs). These coordinators are certified by
taking examinations to see if they are equipped with specialized knowledge and
communication skills. The small number of organs available for transplant poses a
serious problem. In many cases, medical personnel are not proficient enough to
recommend organ donations to the family members of potential donors. Thus, the
role of CPTC includes education of health professionals. In one study, 95% of the
donor family members felt that hospital staff members explained about
transplantation well, while 67% of the nondonor family members felt the same. The
concept of "brain death" was not fully understood by some of the latter. The
timing and place of discussion as well as the skill levels of medical staffs
(preferably CPTCs) were important in receiving the consent. It is necessary for
the donor family members to understand the concept of "death". Communications
between the hospital staff and family members are critical. In Japan, there is no
solid foundation for pediatric organ transplantation. Specialized nurses in
pediatrics are limited. Further, there is meager certification programs for CPTCs
or CCTCs. Under the present state, nurses in ICU and pediatric wards may act as
potential coordinators. Education of these nurses will be critical to increase
the number of pediatric organ transplantation.
PMID- 11004843
TI - [New possibilities for treatment of allergic inflammation in asthma].
PMID- 11004844
TI - [Pseudomonas aerogunosa pneumonia in patients treated at the Hospital for Chest
Diseases].
AB - Retrospective analysis of pneumonia caused by Pseudomonas aeruginosa was made in
66 patients, treated in hospital. Nosocomial pneumonia was diagnosed in 11 (17%)
patients. In 51 patients coexisting lung diseases were present: mainly COPD and
bronchiectasis. Strains of Pseudomonas aeruginosa were susceptible mostly to
imipenem, meropenem, aztreonam, ticarcillin-clavulanic acid, ceftazidime,
ciprofloxacin, amikacin, piperacillin-tazobactam, netilmicin. Duration of
treatment in hospital was very long--59% were treated over 30 days. Combined
antibacterial therapy was applied in 35 (53%) patients and monotherapy, often
with different antibiotics--in 31 (47%) patients. Treatment was successful in 45
(68%) patients. In 9 patients the results of treatment was not successful: mainly
because of empyema in 7 pts. Twelve (18%) patients (with coexisting COPD--6 and
lung cancer--6) died. We can support current recommendations for treatment of
Pseudomonas aeruginosa infection with combination of aminoglycosides or
fluoroquinolones plus one of remaining antipseudomonal antibiotics. Treatment
failures occurred mainly in patients with severe coexisting diseases and/or
empyema.
PMID- 11004845
TI - [Cytoimmunologic changes in material obtained from bronchoalveolar lavage (BAL)
in asymptomatic individuals chronically exposed to silica dust].
AB - The aim of this study was to determine and to evaluate silica induced lung cell
reactivity--if any--in bronchoalveolar space, before clinical changes develop.
Bronchoalveolar lavage (BAL) was carried out in 15 nonsmoking individuals with
chronic professional silica exposure, free of lung signs and symptoms. Controls
were healthy nonsmokers. Routine BAL cytology (HE, MGG) was completed by mast
cell staining (toluidine blue). BAL lymphocyte subsets were phenotyped by direct
two- and three-color immunofluorescence (applied DAKO A/S monoclonal antibodies:
anti-CD3, CD4, CD8, CD11b, CD14, CD15, CD16 + 56, CD19, CD25, CD45, HLA-DR).
Parallel staining was performed in peripheral blood. In individuals with chronic
silica exposure we found: significant increase in alveolar macrophage (362 +/- 45
vs 160 +/- 33 x 10(3) cells/ml, p < 0.05), lymphocyte (61 +/- 9 vs 24 +/- 5 x
10(3) cells/ml, p < 0.05) and BAL total cell (415 +/- 76 vs 187 +/- 34 x 10(3)
cells/ml, p < 0.05) numbers; significant increase in mast cell (0.4 +/- 0.1 vs
0.2 +/- 0.1, p < 0.05), NK cell (7.0 +/- 1.8 vs 3.6 +/- 1.0, p < 0.05) and Th
early activated lymphocyte percent (CD4 + CD25+ calculated as percentage of CD4+
cells: 15.1 +/- 1.5 vs 7.8 +/- 1.6, p < 0.01). All results were presented as
median +/- SEM. Bronchoalveolar space of people with chronic silica exposure
usually shows pathological reaction (especially macrophagic alveolitis), although
they are free of manifested pulmonary disease. Th early activated lymphocytes, NK
cells and mast cells seem to play important role in the early interstitial lung
tissue reaction to silica.
PMID- 11004846
TI - [Proangiogenic cytokines (bFGF and VEGF) in BALF from two different lung segments
examined by high resolution computed tomography (HRCT) in patients with
sarcoidosis].
AB - The aim of the study was to evaluate the concentrations of bFGF and VEGF in
double BAL (2 x 120 ml) from two different lung segments: (s.A) from upper lobe
with the most and (s.B) from lower lobe with the least extensive involvement
estimated by high resolution computed tomography (HRCT). Examined group consisted
of 28 sarcoid patients with homogeneous, regular distribution of nodular
opacities in conventional chest X-ray (14 F, 14 M aged 19-54). Eleven healthy
volunteers served as controls. In patients with sarcoidosis we observed the
significantly higher levels (p < 0.01) of bFGF (1.79 pg/ml, 1.48 pg/ml) and VEGF
(107.5 pg/ml, 109.7 pg/ml) in BAL from s.A and s.B respectively in comparison
with BAL from lung segments Abis and Bbis in control group (bFGF: 0.75 pg/ml,
0.47 pg/ml and VEGF: 33.7 pg/ml, 43.9 pg/ml respectively). bFGF in BAL from s.A
in active sarcoidosis was higher than in s.A and s.B in non-active sarcoidosis.
Concentrations of bFGF in BAL from both s.A and s.B correlated positively with
CD4/CD8 ratio and absolute number of lymphocytes, CD4 cells and lymphocytes HLA
DR estimated in BAL from these lung segments. We conclude that bFGF and VEGF may
be involved in sarcoidosis pathogenesis and bFGF may be useful in estimation of
sarcoidosis activity.
PMID- 11004847
TI - [Detection of tubercle bacilli in clinical samples using genetic
methods(PCR)compared with Lowenstein-Jensen culture methods].
AB - The aim of this work was to compare data obtained using PCR assay for detection
of Mycobacterium tuberculosis with culture. We report a test for detection of
tubercle bacilli by PCR and identification at species level by capture plate
hybridisation and enzyme-linked immunoassay. 222 clinical samples obtained from
patients with confirmed and suspected tuberculosis were analysed. These specimens
were tested parallelly by conventional culture on Lowenstein-Jensen slants and
PCR test. For 205 samples a complete agreement between these methods was
observed.
PMID- 11004848
TI - [Risk factors for airway obstruction in school children with respiratory symptoms
assessed in a five year prospective study].
AB - The aim of this prospective study was to assess age-related changes of the
respiratory status and to evaluate risk factors for persistent airflow
obstruction in symptomatic school children. One hundred fifty children aged 7-12
years (mean age 9.5 yr.) were followed-up. In 1994 parents--administered
questionnaire, skin prick tests and three dynamic spirometries in 4-6 week
intervals were performed. Airways flow limitation was defined as FEV1%, MEF50 or
MEF25 below minimal value. In 1999 questionnaires and spirometry were repeated by
the same methods. The response rate was 74.7%. Children's respiratory status
generally improved. Frequency of respiratory symptoms and obstructive
disturbances (37.5% in 1994 versus 22.3% in 1999) decreased. Significant risk
factors for airways flow limitation in 1999 were nocturnal dry cough, doctor
diagnosed asthma, female gender and parental smoking. Advanced or persisting
airway obstruction during several month in 1994 was valuable to predict lung
function impairment in 1999. No relation between skin tests results and
persistent airway obstruction was observed.
PMID- 11004849
TI - [Sarcoidosis with central nervous system involvement].
AB - A case of pulmonary sarcoidosis with central nervous system involvement was
described. Diagnosis was based on hilar lymph nodes biopsy and OUN MRI scan.
Patient was treated with glicocorticosteroids with improvement.
PMID- 11004850
TI - [Respiratory failure during the course of congenital myopathy effectively treated
with nocturnal noninvasive nasal positive pressure ventilation].
AB - Respiratory muscle weakness in myopathy may result in respiratory failure. 41
year old male with congenital myopathy was successfully treated with nocturnal
noninvasive nasal positive pressure ventilation. NPPV resulted in improvement of
arterial blood gases and allowed to close tracheostomy. Patient was able to
return to full time employment.
PMID- 11004851
TI - [Bone tuberculosis in a patient with pulmonary tuberculosis].
AB - A case of bone tuberculosis in 83 years old farmer was described. He was
hospitalized because of pain, oedema and purulent fistula in carpal regio. He
hadn't neither systemic symptoms neither from respiratory tract. Chest X-ray and
X-ray of carpal bones revealed tuberculous lesions. In the pus from cutaneous
fistula AFB were found in culture. Antituberculous treatment was successful.
PMID- 11004852
TI - [Genetic susceptibility to lung cancer].
PMID- 11004853
TI - [Lymphangioleiomyomatosis].
PMID- 11004854
TI - [Abnormal regulation of coagulation and fibrinolysis in lung cancer].
PMID- 11004855
TI - [Management of coagulation and fibrinolysis disorders in patients with cancer].
PMID- 11004856
TI - [Know the age of your lungs].
PMID- 11004857
TI - [A test for early detection of COPD].
AB - Free spirometry was offered to inhibitants of Bydgoszcz who presented with
chronic cough. 1072 subjects were investigated, 638 males and 433 females, mean
age 54 years. Eighty percent were smokers or exsmokers. In 78.6% subjects
spirometry was normal. 200 persons (18.7%) had spirometric signs of airway
obstruction, 19.5% mild, 51.5% moderate and 29% severe. Mass spirometry of
smokers with chronic cough is a good screenings method for detection of COPD.
PMID- 11004858
TI - [A test for initial diagnosis of COPD in patients with chronic cough and exercise
dyspnea (population study)].
AB - The purpose of the present investigation was to evaluate the usefulness of
spirometry as a screening test in the initial diagnosis of COPD in patients with
chronic cough and exercise dyspnea. We encouraged people living in Lublin to the
participation in this trial using local media. We examined 647 subjects, 329
(51%) females and 318 (49%) males between the ages of 14 and 89 years (average 55
y.). Among females there were: 73 smokers (22%), 51 former smokers (15%) and 205
non smokers (63%), among males respective numbers were: 112 (35.2%), 119 (37.4%
and 87 (27.4%). 230 women (70%) and 230 men (72%) had clinical symptoms of COPD.
The severity of bronchial obstruction was classified according to ERS
recommendations. In females mild obstruction was found in 24 (7.3%), moderate in
80 (24.3%) and severe in 20(6.1%). In men mild obstruction was found in 15
subjects (4.7%), moderate in 80 (24.3%) and severe in 38 (11.9%). CONCLUSIONS: 1.
Spirometry revealed that 35% of all examined subjects had an airway obstruction
in majority of moderate and severe severity. 2. Spirometry is a very good and
sensitive screening test in the diagnosis of COPD.
PMID- 11004859
TI - [Early detection of COPD by high risk population spirometric screening].
AB - COPD is the most frequent chronic lung disease in Poland. The disease is however
under-diagnosed, especially at the early stages. The aim of the study was to
assess the efficacy of spirometric screening for COPD in middle aged smokers.
Informations on causes and symptoms of COPD were disseminated in mass media in 14
large cities. Subject aged over 39 and with smoking history of > 10 packyears
were invited for a free spirometry in local chest clinic. However, everyone
attending had the spirometry performed. Spirometry was performed according to ATS
recommendations. Airway obstruction (AO) was diagnosed when FEV1/FVC < 85% of N
and categorised as mild (FEV1 > 70% of N), moderate (FEV1 50-69% of N) or severe
(FEV1 < 50% of N). Spirometry was accompanied by an antismoking advice. RESULTS:
12.781 subjects were screened (mean age 52 +/- 12 years, 57% males). In 8.269
subjects who complied with inclusion criteria AO was diagnosed in 29.8% (mild in
10.9%, moderate in 12% and severe in 6.9%). In smokers < 40 years of age and a
history of < 10 packyears AO was found in 8.8% (mild in 6.0%, moderate in 1.8%
and severe in 1.0%). CONCLUSION: Mass spirometry is an effective and easy method
for early detection of COPD.
PMID- 11004860
TI - [Evaluation of the influence of tobacco smoking on pulmonary function in youg
men].
AB - According to WHO estimates in the early 1990s there were around 1.100 million
smokers in the world, about one third of the global population over 15 years of
age. The aim of the study was to evaluate tobacco influence on pulmonary function
tests in young healthy men. The study was performed on 3004 subjects 18-23 years
old. The subjects were divided into two groups, smokers (S n = 1726) and non
smokers (NS n = 1278). Each subject had spirometry and body pletysmography done.
The analysis of influence of smoking on pulmonary function tests showed
statistically significant decrease of TLC, FEV1, FEV1%/VC, PEF and FEF50 in the
smokers' group. Percentage of people with airflow limitation (FEV1%VC < 85% N,
FEV1 < 80% N, FEF50 < 70% N) was two times higher than in the non-smokers' group.
IN CONCLUSION: smoking significantly increases the number of subjects with
airflow limitation among healthy young males in Poland.
PMID- 11004861
TI - [Comparison of automatic (AUTO-CPAP)and "manual" CPAP pressure titration in
patients with obstructive sleep apnea].
AB - Auto-CPAP gives an opportunity to decrease costs of evaluating patient with OSA,
replacing manual titration of pressure during PSG. The aim of this study was to
compare automatic (auto-CPAP) and manual CPAP pressure titration in patients with
OSA. We studied 50 obese patients (BMI--35 +/- 6 kg/m2), mean age 52.4 +/- 9.4
years with severe OSA, mean: AHI--62.9 +/- 22.1, mean overnight SaO2--89.1 +/-
3.7%, T90--54.4 +/- 29.6%. Two polysomnographies were performed: first when
patient slept with CPAP and pressure was titrated manually by a technician and
second on auto-CPAP device. Both methods had similar efficacy in reduction of AHI
(< 10/h) and hypoxaemia, despite lower pressure established during auto-CPAP mode
preventing apnoeas and hypopnoes during 90% of sleep time (8.2 +/- 1.7 cm H2O)
compared to manual CPAP titration (9.2 +/- 1.7 cm H2O) (p < 0.05). CONCLUSION:
Auto-CPAP seems to be a reliable alternative to manual titration of the
therapeutic pressure in patients with OSA. This may help to cut a waiting list
for PSG of patients suspected of OSA.
PMID- 11004862
TI - [Obstructive sleep apnea and risk factors for coronary artery disease].
AB - STUDY AIM: Obstructive sleep apnoea (OSA) is strongly associated with obesity,
especially abdominal obesity. Obesity in turn is a well-known risk factor for
coronary artery disease (CAD). The aim of our study was to evaluate the
relationship between OSA severity and CAD risk factors. MATERIAL AND METHODS: The
sample consisted of 73 subjects (mean age +/- SE, 46.7 +/- 1 years) referred to a
sleep laboratory. Subjects were either: 1. obese with OSA (O-OSA group n = 35;
body mass index, BMI l 30 kg/m2; apnoea/hypopnoea index, AHI > 35), 2. non-obese
with OSA (BO-OSA group n = 14; BMI < 27 kg/m2; AHI > 35), or 3. obese without OSA
(O-Z group n = 24; BMI l 30 kg/m2; AHI < 5). All subjects underwent full
overnight polysomnography. Blood samples were taken from all subject, for fasting
levels of insulin (INS), glucose (GLU), total, HDL and LDL cholesterol,
triglyceride (TG) and uric acid (UA). RESULTS: O-OSA had significantly higher INS
and UA levels (p < 0.05) compared to BO-OSA and O-Z. GLU and lipid levels were
comparable in the studied groups. GLU level correlated (p < 0.05) negatively to
minimum oxyhemoglobin saturation (SAT-MIN) and positively to neck circumference.
TG and UA levels were correlated (p < 0.05) positively to AHI and negatively to
SAT-MIN. UA level was also positively correlated (p < 0.05) to BMI, waist/hip
circumference ratio (WHR), and INS level. INS level correlated (p < 0.05)
positively to AHI, T90, WHR and UA, and negatively to SAT-MIN and mean
oxyhemoglobin saturation. After adjusting for the influence of OSA and obesity
(multiple regression analysis), we found independent negative correlations (p <
0.05) between: GLU level and SAT-MIN, UA level and SAT-MIN, and INS level and SAT
MIN. An independent, positive correlation (p < 0.05) was found between TG level
and AHI. CONCLUSIONS: Results of our study suggest that OSA increases the risk of
coronary artery disease by increasing plasma levels of glucose, triglyceride and
insulin, independent of obesity.
PMID- 11004863
TI - [Malfunction of some immunologic functions in patients with obstructive sleep
apnea].
AB - Hypoxia and sleep disorders may result in an impairment of immune system in
patients with obstructive sleep apnea (OSA). Therefore we studied mitogenic
stimulation of peripheral blood lymphocytes by PHA (1 microgram/ml) by
measurement of 3H-thymidine incorporation, metabolic activity of neutrophils
measured by chemiluminescence (CL), immunoglobulins (IgG, IgA and IgM)
concentration in serum (radial immunodiffusion) and TNF-alpha concentration in
serum (ELISA), and E-rosette tests (with theophylline) in 57 obese patients with
severe OSA. In OSA patients severe impairment of f-MLP-induced granulocyte
chemiluminescent activity was observed.
PMID- 11004864
TI - [Chronic Chlamydia pneumoniae infection in patients with asthma].
AB - The aim of our study was to evaluate the frequency of Chlamydia pneumoniae
infection (especially chronic infection) in 41 asthma patients. They have been
assigned to 3 groups, according to disease severity. Control group consisted of
35 age matched healthy volunteers (without cardiac and pulmonary diseases). The
levels of specific IgG, IgA and IgM in patients' serum have been estimated using
indirect microimmunofluorescence. According to serologic criteria, 23(56.1%)
asthma patients and 4(11.4%) healthy controls have appeared to be chronically
infected with Chlamydia pneumoniae (p < 0.001). Acute Chlamydia pneumoniae
infection was present in 3(7.3%) asthma patients and in 2(5.7%) healthy controls.
Taking in account asthma severity, persistent Chlamydia pneumoniae infection has
occurred more frequently in patients with moderate and severe asthma than in ones
with mild asthma. Acute Chlamydia pneumoniae infection was present in 9.1% and
12.5% of patients with mild and severe asthma respectively.
PMID- 11004865
TI - [Chronic Chlamydia pneumonia infection in patients with chronic obstructive
pulmonary disease].
AB - The aim of our study was to evaluate the frequency of Chlamydia pneumoniae
infection (especially chronic infection) in COPD patients.
Microimmunofluorescence method has been applied Chlamydia pneumoniae Micro-IF
test (Labsystems) has been used. The levels of specific IgG, IgA and IgM have
been estimated in patients' serum. According to serologic criteria, 64.1% of COPD
patients and 20.5% of healthy controls appeared to be chronically infected with
Chlamydia pneumoniae (p < 0.001). Taking in account COPD severity, persistent
Chlamydia pneumoniae infection has been present in 68.2%, 57.1%, and 50% of
patients with severe, moderate and mild COPD, respectively. Our study has
revealed that chronic Chlamydia pneumoniae infection occurs more frequently in
COPD patients than in healthy controls and in patients with severe COPD than in
ones with mild and moderate disease. It is possible that persistent Chlamydia
pneumoniae infection can initiate or amplify inflammatory reactions in the
respiratory tract. The results suggest a need to diagnose chronic Chlamydia
pneumoniae infection in COPD patients and, if confirmed, to take an attempt of
antimicrobial therapy.
PMID- 11004866
TI - [Lung changes during the course of non-Hodgkin's lymphoma in a patient with
rhematoid arthritis with secondary Sjogren's syndrome].
AB - A case of 51 years old woman with 12-years history of rheumatoid arthritis and
secondary Sjoegren's syndrome, who developed EBV-associated diffuse large B-cell
lymphoma (Lymphomatoid granulomatosis type) involving lungs, lymph nodes and bone
marrow was described.
PMID- 11004867
TI - [Granulomatous lung lesions after occupational exposure to glass fibers].
AB - 39 years old man with granulomatous lesions in both lungs caused by occupational
contact with glass fibers was described. He has been working as an bricklayer
plasterer for 18 years and was in contact with lime, cement, plaster, asbestos,
dust of coal and wood and with glass fibers. For the last two years before
admission in 1993 he has had frequent bronchial infections. On admission he was
in good general condition, his spirometric examination and blood gases were
within normal limits. On chest x-ray disseminated lesions were found. Those
lesions were of the round shapes on chest CT. Many sputum cultures for tubercle
bacilli were negative. ANA and ANCA were not found in the serum. ACE was within
normal limits. No precipitins to environmental antigens were found. Cancer
metastases were suspected and lung biopsy during videothoracoscopy was done. Many
foreign body type granulomas were found throughout the specimen. The character of
the lesions was not typical for tuberculosis, sarcoidosis, extrinsic allergic
alveolitis, silicosis or asbestosis. There are some reports concerning the
possibility of development of such lesions after the exposition to glass fibers.
We suspect that case is an example of such pathology. His occupational exposition
was stopped in 1993 and he was observed without treatment. During the 5 years of
observation (up till 1998) he was in good health with stable chest x-ray picture
and results of respiratory system function.
PMID- 11004868
TI - [The role of infection in chronic obstructive pulmonary disease].
PMID- 11004869
TI - [The role of anticholinergics in treatment of diffuse airway obstruction].
PMID- 11004870
TI - The proof of the pudding: an illustration of the relative strengths of null
hypothesis, meta-analysis, and Bayesian analysis.
AB - Some methodologists have recently suggested that scientific psychology's over
reliance on null hypothesis significance testing (NHST) impedes the progress of
the discipline. In response, a number of defenders have maintained that NHST
continues to play a vital role in psychological research. Both sides of the
argument to date have been presented abstractly. The authors take a different
approach to this issue by illustrating the use of NHST along with 2 possible
alternatives (meta-analysis as a primary data analysis strategy and Bayesian
approaches) in a series of 3 studies. Comparing and contrasting the approaches on
actual data brings out the strengths and weaknesses of each approach. The
exercise demonstrates that the approaches are not mutually exclusive but instead
can be used to complement one another.
PMID- 11004872
TI - Coefficient alpha and related internal consistency reliability coefficients.
AB - The author studied the conditions under which coefficient alpha and 10 related
internal consistency reliability coefficients underestimate the reliability of a
measure. Simulated data showed that alpha, though reasonably robust when computed
on n components in moderately heterogeneous data, can under certain conditions
seriously underestimate the reliability of a measure. Consequently, alpha, when
used in corrections for attenuation, can result in nontrivial overestimation of
the corrected correlation. Most of the coefficients studied, including lambda 2,
did not improve the estimate to any great extent when the data were
heterogeneous. The exceptions were stratified alpha and maximal reliability,
which performed well when the components were grouped into two subsets, each
measuring a different factor, and maximized lambda 4, which provided the most
consistently accurate estimate of the reliability in all simulations studied.
PMID- 11004871
TI - Effects of directionality of significance tests on the bias of accessible effect
sizes.
AB - The proportion of studies that use one-tailed statistical significance tests (pi)
in a population of studies targeted by a meta-analysis can affect the bias of the
sample effect sizes (sample ESs, or ds) that are accessible to the meta-analyst.
H. C. Kraemer, C. Gardner, J. O. Brooks, and J. A. Yesavage (1998) found that,
assuming pi = 1.0, for small studies (small Ns) the overestimation bias was large
for small population ESs (delta < or = 0.2) and reached a maximum for the
smallest population ES (viz., delta = 0). The present article shows (with a minor
modification of H. C. Kraemer et al.'s model) that when pi = 0, the small-N bias
of accessible sample ESs is relatively small for delta < or = 0.2, and a minimum
(in fact, nonexistent) for delta = 0. Implications are discussed for
interpretations of meta-analyses of (a) therapy efficacy and therapy
effectiveness studies, (b) comparative outcome studies, and (c) studies targeting
small but important population ESs.
PMID- 11004873
TI - Large-sample confidence intervals for validity and reliability coefficients.
AB - Large-sample confidence intervals (CI) for reliability, validity, and
unattenuated validity are presented. The CI for unattenuated validity is based on
the Bonferroni inequality, which relies on one CI for test-retest reliability and
one for validity. Covered are four reliability-validity situations: (a) both
estimates were from random samples; (b) reliability was from a random sample but
validity was from a selected sample; (c) validity was from a random sample but
reliability was from a selected sample; and (d) both estimates were from selected
samples. All CIs were evaluated by using a simulation. CIs on reliability,
validity, or unattenuated validity are accurate as long as selection ratio is at
least 20% and selected sample size is 100 or larger. When selection ratio is less
than 20%, estimators tend to underestimate their parameters.
PMID- 11004874
TI - How important is transient error in estimating reliability? Going beyond
simulation studies.
AB - This article introduces a procedure for estimating reliability in which
equivalent halves of a given test are systematically created and then
administered a few days apart so that transient error can be included in the
error calculus. The procedure not only estimates complete reliability (taking
into account both specific-factor error and transient error) but also can
estimate partial reliability (taking into account only specific-factor error).
Scores from 6 different measuring instruments were analyzed with the procedure.
The results indicate that the magnitude of transient error in real data can range
from nonexistent to very large. It follows that traditional reliability
estimates, using nonstaggered procedures, are inflated to the extent that
transient error is present.
PMID- 11004875
TI - Modeling stage-sequential change in ordered categorical responses.
AB - Although few would dispute the usefulness of looking at behavioral change from a
stage-sequential perspective, until recently the lack of appropriate modeling
techniques has hampered rigorous empirical tests of stage theories. In
particular, for behavioral measurements that are ordinal, there is a need for
methods that represent the underlying change processes in the form of qualitative
and discontinuous shifts. This article introduces a stage-sequential ordinal
model by postulating that at any point in time there are a finite number of
latent stages. Panel members may shift among these stages over time. The authors
show that the stage-sequential model provides a general approach for both the
analysis of ordinal time-dependent data and tests of various competing theories
and hypotheses about psychological change processes. An analysis of a 5-year
study concerning attitudes toward alcohol consumption by teenagers is presented
to illustrate the modeling approach.
PMID- 11004876
TI - Executive processing.
PMID- 11004877
TI - Task switching and the measurement of "switch costs".
AB - The measurement of "switch costs" is held to be of interest because, as is widely
believed, they may reflect the control processes that are engaged when subjects
switch between two (or more) competing tasks. [In task-switching experiments, the
reaction time (RT) switch cost is typically measured as the difference in RT
between switch and non-switch (repeat) trials.] In this report we focus on the RT
switch costs that remain even after the subject has had some time to prepare for
the shift of task, when the switch cost may be approximately asymptotic (so
called residual switch costs). Three experiments are presented. All three
experiments used Stroop colour/word, and neutral stimuli. Participants performed
the two tasks of word-reading and colour-naming in a regular, double alternation,
using the "alternating runs" paradigm (R. D. Rogers & S. Monsell, 1995). The
experiments were designed to test the hypothesis that RT switch costs depend on a
form of proactive interference (PI) arising from the performance of a prior,
competing task. A. Allport, E. A. Styles and S. Hsieh (1994) suggested that these
PI effects resulted from "task-set inertia", that is, the persisting activation
suppression of competing task-sets, or competing task-processing pathways. The
results confirmed the existence of long-lasting PI from the competing task as a
major contributor to switch costs. Non-switch trials, used as the baseline in the
measurement of switch costs, were also shown to be strongly affected by similar
PI effects. However, task-set inertia was not sufficient to account for these
results. The results appeared inconsistent also with all other previous models of
task switching. A new hypothesis to explain these between-task interference
effects was developed, based on the stimulus-triggered retrieval of competing
stimulus-response (S-R) associations, acquired (or strengthened) in earlier
trials. Consistent with this retrieval hypothesis, switch costs were shown to
depend primarily on the S-R characteristics of the preceding task (the task that
was switched from) rather than the upcoming task. Further, the effects of the
other, competing task were found to persist over many successive switching
trials, affecting switch costs long after the stimulus overlap (and hence the
principal S-R competition) between the current tasks had been removed. Switch
costs were also found to be affected by recent, item-specific experience with a
given stimulus, in either the same or the competing task. Finally, the results
showed that switch costs were massively affected by the ratio of the number of
prior trials, in response to the same stimuli, that had implemented either the
currently intended or the competing S-R mappings. None of these effects are
predicted by current models of residual switch costs, which appeal to the
differences in control processes assumed to be engaged in switch versus non
switch trials.
PMID- 11004878
TI - Modeling cognitive control in task-switching.
AB - This article describes a quantitative model, which suggests what the underlying
mechanisms of cognitive control in a particular task-switching paradigm are, with
relevance to task-switching performance in general. It is suggested that
participants dynamically control response accuracy by selective attention, in the
particular paradigm being used, by controlling stimulus representation. They are
less efficient in dynamically controlling response representation. The model fits
reasonably well the pattern of reaction time results concerning task switching,
congruency, cue-target interval and response-repetition in a mixed task
condition, as well as the differences between mixed task and pure task
conditions.
PMID- 11004879
TI - Reconfiguration of task-set: is it easier to switch to the weaker task?
AB - Switching between two tasks afforded by the same stimuli results in slower
reactions and more errors on the first stimulus after the task changes. This
"switch cost" is reduced, but not usually eliminated, by the opportunity to
prepare for a task switch. While there is agreement that this preparation effect
indexes a control process performed before the stimulus, the "residual" cost has
been attributed to several sources: to a control process essential for task-set
reconfiguration that can be carried out only after the stimulus onset, to
probabilistic failure to engage in preparation prior to the stimulus, and to two
kinds of priming from previous trials: positive priming of the now-irrelevant
task set and inhibition of the now-relevant task-set. The main evidence for the
carry-over of inhibition is the observation that it is easier to switch from the
stronger to the weaker of a pair of tasks afforded by the stimulus than vice
versa. We survey available data on interactions between task switching and three
manipulations of relative task strength: pre-experimental experience, stimulus
response compatibility, and intra-experimental practice. We conclude that it is
far from universally true that it is easier to switch to the weaker task. Either
inhibition of the stronger task-set is a strategy used only in the special case
of extreme inequality in strength, or its consequences for later performance may
be masked by slower post-stimulus control operations for more complex tasks.
Inhibitory priming may also be stimulus specific.
PMID- 11004880
TI - Rehabilitation of executive deficits in closed head injury and anterior
communicating artery aneurysm patients.
AB - This paper reports a study that was aimed to rehabilitate executive functions in
closed head injury (CHI) and anterior communicating artery (ACoA) aneurysm
patients. The groups tested comprised 10 CHI patients, 9 ACoA aneurysm patients
and 19 controls. We employed a dual-task paradigm that is known to tap the
ability to co-ordinate two actions. The treatment consisted of five experimental
sessions, in which the dual-task paradigm was used. In the CHI study, the dual
task cost was measured before the treatment (assessment), immediately after the
treatment (retest), and 3 months after the treatment (follow-up). In the ACoA
aneurysm study, the dual-task cost was also assessed 12 months after the
treatment. A significant reduction of the dual-task cost from assessment to
retest was found. This reduction remained stable in the follow-up sessions. The
results are discussed with reference to the absence of spontaneous recovery of
this specific executive function and to the possibility that the beneficial
effect of the treatment generalises to other executive functions and/or daily
living activities.
PMID- 11004881
TI - Strategy application disorder: the role of the frontal lobes in human
multitasking.
AB - Strategy application disorder is a term used to describe a pattern of deficits,
usually associated with frontal lobe dysfunction, where people show
disorganisation, absentmindedness and problems with planning and decision making
in everyday life despite normal performance on traditional neuropsychological
tests. It is argued that the prototypical situation which presents problems for
these cases are those which require multitasking, and although good cases are
rare in the literature, those that do exist show a characteristic
neuropsychological pattern. Moreover, this pattern is confirmed in recent group
studies of multitasking and of the relationship between multitasking tests (such
as the Six Element Test), failures in everyday life and other neuropsychological
measures. At present the evidence suggests that the potential frontal brain
regions most implicated in multitasking are the anterior cingulate; B.A. 10 and
immediately adjacent areas; and the right dorsolateral prefrontal cortex, with
each making a unique contribution to different aspects of performance.
Furthermore, recent studies show striking dissociations between performances on
multitasking tests and two of the most commonly administered measures of
executive function: the verbal fluency test and the Wisconsin Card Sorting Test,
which sets a minimum level for a fractionation of the executive syndrome in
humans.
PMID- 11004882
TI - Executive functions and the frontal lobes: a conceptual view.
AB - Several problems in understanding executive functions and their relationships to
the frontal lobes are discussed. Data are then presented from several of our
studies to support the following statements: (1) the examination of patients with
focal frontal lobe lesions is a necessary first step in defining the relation of
executive functions to the frontal lobes; (2) there is no unitary executive
function. Rather, distinct processes related to the frontal lobes can be
differentiated which converge on a general concept of control functions; (3) a
simple control-automatic distinction is inadequate to explain the complexity of
control-automatic processes; (4) the distinction between complex and simple tasks
cannot explain the differences in functions between the frontal lobes and other
brain regions; and (5) the most important role of the frontal lobes may be for
affective responsiveness, social and personality development, and self-awareness
and unconsciousness.
PMID- 11004883
TI - Neural control of behavior: countermanding eye movements.
AB - Understanding the self-control of action entails knowledge about how actions are
initiated, how planned actions are canceled and how the consequences of actions
are registered. We have investigated neural correlates of these processes using
the countermanding paradigm--a task that required subjects to occasionally cancel
a planned speeded response, and an analysis that provides an estimate of the time
needed to cancel a planned movement. By monitoring the activity of single neurons
in the frontal cortex of macaque monkeys performing this task we have
distinguished signals responding to the visual stimuli, other signals that
control the production of movements, and still other signals that seem to monitor
behavior.
PMID- 11004884
TI - Patterns of cognitive ageing.
AB - Neuroanatomical evidence suggests that normal ageing affects some brain areas,
and the "local" functions they support, earlier and more severely than others.
Changes appear to be especially marked in the hippocampus, temporal association
and prefrontal cortex. Evidence from classical neuropsychological studies
suggests that these brain areas are associated with memory and "executive"
functions, respectively. We may, therefore, expect that tests purported to
measure these functions may be disproportionately affected in old age and that
there may be evidence for some separation of these functions even within
neurologically normal populations. What we also know, however, is that measures
reflecting general fluid ability also decline with increasing age, so any
hypothesis relating to specific "local" deficits must acknowledge and account for
any "globar" changes in performance. Volunteers (n = 162) aged between 60-80
years who had completed the Cattell and Cattell Culture Fair Intelligence Test
(CCF) completed the Cambridge Automated Neuropsychological Test Battery (CANTAB).
The CANTAB has been administered to several patient populations and tests from
the battery have been shown to be sensitive to damage in both temporal and
prefrontal areas (Owen et al., 1996). Results from the test battery showed that
both the Paired Associate Learning and Spatial Recognition tests were the most
sensitive to normal ageing even when CCF is accounted for. In contrast, this
performance on the "executive" tests, shown to be sensitive to frontal lobe
damage was not related to age, and CCF scores predicted performance on these
tests. These results are discussed in relation to theories of cognitive ageing
and patterns of change and in relation to several important methodological and
theoretical considerations for the study of executive function.
PMID- 11004885
TI - [The "international" of psychodynamic psychotherapy researchers].
PMID- 11004886
TI - [Illness-coping in a population-based representative sample. Situational,
sociodemographic and social influences].
AB - In spite of the considerable volume of current coping research there is a
noticeable lack of studies based on large representative samples. In this study a
sample of 2179 subjects of 16 to 96 years of age that was representative of the
entire population of Germany, was asked as to how they now cope, how they have
coped in the past or how they would cope with: 1. an existing illness, 2. a past
illness and 3. an imagined (non-existent) illness. The instrument used was the
questionnaire version of the "Berner Bewaltigungsformen" (BEFO), a coping
questionnaire with 28 systematically derived coping dimensions that are defined
independently of the usual empirical-topographical dimensions (behavioural,
cognitive and emotional) of the type of illness. The enquiry was concerned with
the influence of varying situational (proximity of illness, subjective evaluation
of personal health, psychological symptoms), socio-demographic (age, gender) and
social (social support) variables on the choice of coping mechanisms. The results
showed that each of these factors influences the repertoire of coping mechanisms
to varying degrees. This systematic variability in a representative sample should
be taken into account in any evaluation of coping with illness in clinical sub
groups.
PMID- 11004887
TI - [Results of an evaluation of psychotherapeutic care from the viewpoints of
patients and therapists in Saxony-Anhalt].
AB - With the enforcement of the German law for psychotherapeutics at the beginning of
1999, the field of psychotherapy detached from a widespread "delegation
procedure" through the possibility of first-access for patients to a
psychotherapist. In the form of an experiment, Saxony-Anhalt practiced as the
only land in the Feral Republic of Germany a modified form of delegation
procedure in the legal health insurance since 1992. The most important
modification consisted in the possibility of first-access for the patient to the
psychotherapist. Using selected results of the investigation in the view of
psychotherapy patients and from medical and psychological psychotherapists, the
situation after 5 years since introduction of this model in the out-patient,
psychotherapeutic care in Saxony-Anhalt will be shown, as well as experience
gained from this model.
PMID- 11004888
TI - [Self concept and object relations of patients with affective disorders-
individual centered diagnosis with the repertory-grid technique].
AB - Significant dimensions of the self concept and the object relations of 127
depressive patients and 34 orthopaedic patients were investigated with the
repertory-grid-technique. Self concept and object relations were compared by
means of nomothethically used idiographic results after recovery from manifest
depression. The object relations of the depressive sample were characterised by
the dimension "symbiotic near"; "ambivalent" and "indifferent" partnership
relationships were found much more frequently in the controls. The idiographic
results contribute to a differentiation of the spectrum of affective disorders.
They underline the importance of the interpersonal dimension of depression and
may be used as a basis of a therapeutic orientation.
PMID- 11004889
TI - [Catamnestic study of ecological brief therapy].
AB - Ecological brief psychotherapy has been practised at the Psychiatric Outpatient
Clinic at the University Hospital Zurich since 1990. The aim is to use the
development-oriented challenges posed by important others in the therapeutic
process. The effectiveness of this form of therapy is investigated by reviewing
the outcome of 28 completed treatment cases. While results at completion of
therapy come up to the expectations, the long-term results were surprisingly
positive. 96.4% of those surveyed reported they felt considerably better at final
assessment 1 to 6 years after the therapy than they did at the beginning.
Positive changes continued after the completion of therapy. We presume that our
coevolutive focus brought resolution of blocked developmental steps in
relationships that further stimulated changes that continued after the conclusion
of therapy, even without further therapeutic support. Furthermore, the treatment
effects provided by ecological brief psychotherapy apply to personality disorders
as well.
PMID- 11004890
TI - [Rabies-free status of Switzerland following 30 years of rabies in foxes].
AB - The European fox rabies epizootic starting in 1939 at the eastern border of
Poland reached Switzerland on March 3, 1967. Rabies spread over large parts of
the country until 1977, the year it caused three human deaths. In 1978 the first
field trial world-wide for the oral immunization of foxes against rabies was
conducted in Switzerland. Initially, the expansion of the vaccination area led to
a rapid reduction in rabies cases. However, the 1990s were characterized by a
recrudescence of rabies in spite of regular oral immunization of foxes. The last
endemic case of rabies was diagnosed in 1996 after an adaptation of the
vaccination strategy. A total of 17,109 rabies cases, of which 73% in foxes and
14% in domestic animals were diagnosed, leading to an estimated number of some
25,000 postexposure treatments in humans. To eliminate rabies, a total of 2.8
million baits containing a modified live virus were distributed--mostly by hand-
in the field.
PMID- 11004891
TI - [The development of rabies in Switzerland--landscape determines the spread of a
wildlife epidemic].
AB - The rabies epidemic that reached Switzerland in 1967 developed in response to
landscape factors as long as no efficient control strategies were available. The
landscape acted either as barrier to the spread of rabies, or it influenced the
density of red foxes and thus the habitat of the epidemic. Following the first
cases in the canton of Schaffhausen, the whole northwestern Switzerland was
infected followed by the eastern Alps, large parts of the Plateau and the Jura
mountains. In 1978, in the canton of Valais, the first campaigns of oral
immunization of foxes against rabies started. The design of vaccination campaigns
during the next two decades was always closely linked to landscape features.
Thus, it was possible to free first the Alps and then the Plateau from rabies and
finally, at the end of the 1990s, to eliminate it completely within the country.
We describe the entire development of the epidemic within the period of 30 years
from the first infection up to the last registered case and the final vaccination
campaign.
PMID- 11004892
TI - [The development of strategies for the field application of oral immunization of
foxes against rabies].
AB - Preconditions for successful field application of the idea to orally immunize
foxes against rabies were a) the development of an efficacious and safe vaccine
and an attractive bait and b) a suitable strategy to reach a high proportion of
the vector population with vaccine-ladden baits. A geographical and
epidemiological concept on how to implement the vaccination strategy and how to
achieve a sufficiently high level of surveillance were further cornerstones
contributing to the success of the method. Finally, political decisions and a
legal basis for the application of the method of oral immunization were required
to eradicate fox rabies in Switzerland.
PMID- 11004893
TI - [The final stage of rabies in Switzerland].
AB - Since summer 1989, rabies in Switzerland has been restricted to the Jura
Mountains in the north-west of the country. Even there, the last endemic focus
disappeared in 1990, but a re-infection in the same year caused a new flare-up of
the epizootic. Until 1994, the number of rabies cases increased again to 225.
Control measures were intensified with doubled vaccination campaigns, increased
bait densities, and additional vaccination campaigns to immunize young foxes at
the den. As a consequence, the number of cases dropped to 25 in 1995 and to 6 in
1996. On December 21, 1996, the last endemic case of rabies in Switzerland was
registered. After two years of continuing vaccination campaigns and surveillance,
Switzerland became officially rabies-free at the beginning of 1999. In the
present paper, we analyse the final stage of the epizootic. The re-infection in
1990 was caused by infected foxes immigrating from France, but as the
immunization of the fox population in Switzerland was insufficient, the disease
became again endemic immediately. The lacking herd immunity was partly a
consequence of problems related to the vaccination system and even more of the
rapid increase of the fox population.
PMID- 11004894
TI - Oral immunization against rabies: afterthoughts and foresight.
AB - The article contains personal views on some issues that are frequently addressed
in discussions about rabies control, and on some related topics that are often
overlooked. The first field applications of oral wildlife rabies immunization in
the Swiss Rhone Valley were preceded by many years of international cooperative
studies on efficacy and safety. They were significant "faits accomplis" that
facilitated similar endeavors in other countries. Some aspects of the residual
pathogenicity of oral rabies vaccines are discussed. The field efficacy of oral
wildlife immunization is the outcome of complex interactions between vaccine and
bait attributes, bait distribution procedures, and habitat properties.
Significant difficulties hinder the interpretation of field observations on
efficacy. Though oral wildlife immunization is not an animal welfare act and not
a conservationist achievement, it is an attempt at zoonosis control intended to
protect human health and prevent economic losses.
PMID- 11004895
TI - [The Caucasus: recurrence of rabies in Georgia].
PMID- 11004896
TI - [The last case of canine rabies in Switzerland].
PMID- 11004897
TI - MedBytes.
PMID- 11004898
TI - Certifying death.
PMID- 11004899
TI - Death by chocolate?
PMID- 11004900
TI - Negotiating with insurers.
PMID- 11004901
TI - The gene machine.
PMID- 11004902
TI - A physician's guide to the human genome.
PMID- 11004903
TI - Presidential health.
PMID- 11004904
TI - Differential diagnosis and management of an infant presenting in shock with a
history of sickle cell anemia and a recent fall.
AB - The presentation of shock in an infant can be subtle, yet must be recognized and
treated very quickly to prevent decompensation and cardiopulmonary arrest.
Treatment must begin as soon as shock is noted and before or along with the
evaluation to establish the etiology of the shock. This case report illustrates
these principles by describing an infant with sickle cell anemia who presented to
the emergency department in shock after sustaining a fall.
PMID- 11004905
TI - [The immunological basis of the administration of DTP-polio vaccine].
AB - The main subject of this essay is the analysis of the immunizing properties and
possible side effects of DTP (whole cell)-polio vaccine, which since 1964 is the
backbone of the immunization programme in the Netherlands. The concept, that the
basis of the immunity conferred by diphtheria and tetanus toxoid and inactivated
poliovirus is humoral, is now generally accepted. Assessment of the potency of
these three components is based on their binding properties to specific
immunoglobulines in standard-antisera. An example is the testing of neutralising
antibodies against the three types of poliovirus in sera obtained from different
groups of infants injected with increasing doses of this vaccine. Side-effects
after injecting diphtheria- and tetanus toxoids and three types inactivated
poliovaccine are negligible. For the pertussis component of the vaccine, this is
not the case. The standardization of the potency of cellular pertussis vaccine is
still based on the analysis of the protective capacity of a number of plain
vaccine lots in the intercerebral mouse-protection test relative to the
protection they confer in children. An international standard vaccine is
available for this purpose, and the potency of individual lots can be expressed
in International Units. At present acellular pertussis vaccines are also
available for immunization against this disease. The components of such vaccines
are at least for a number of components, arbitrarily chosen. Recently in a trial
in Sweden, a five-component pertussis vaccine has given a similar protection of
infants as a cellular vaccine of British origin. In addition this acellular
vaccine induced less febrile reactions. However, acellular vaccines do not
protect mice against intracerebral infection. because producers have decided to
omit the "Outer Membrane Complex (OMC) as a component of the vaccine. In addition
it has recently been shown that the presence of the cellular pertussis component
in DPT vaccine will almost completely suppress tetanus antitoxins in the IgE
fraction of the serum. This observation could indicate that this suppression is
the result of a cellular immunity reaction by components in the bacteria.
PMID- 11004906
TI - [Vaccination policy in Flanders].
AB - In the recent past (1997) the Flemish authorities have turned the vaccination
policy into one of the top priorities of their health policy. Following the WHO
guidelines they have brought forward a health objective anticipating a
significant increase of the vaccination rate for a number of infectious diseases
by 2002. Recent research shows that attention should be paid especially to
measles, mumps and rubella (83% vaccination rate at 18-24 months), hepatitis B
(74-69%) and type b haemophilus influenzae (78%). The vaccination rate in
Flanders for polio, diphtheria, tetanus and whooping cough is good or adequate at
the age of 18-24 months. In 2000, the Flemish authorities reserve about BEF 80
million for the purchase of basic vaccines distributed for free through their
health inspections, just like in the previous years. In order to realise this
objective, all medical bodies carrying responsibility in this field are appealed
to. Moreover, the local regional consultative bodies, financially supported by
the Flemish Community, may be expected to play a stimulating role in, so far,
four out of the five Flemish provinces. A strong management from a central
Flemish vaccination umbrella organisation is considered to be indispensable in
order to have the vaccinating bodies deliberate, have them build a consensus and
motivate them. This should result in clear and generally accepted vaccination
schedules and a well-informed and sensitised population. A project in view of a
rapid and efficient registration of vaccination data in a central Flemish
vaccination database, accessible for vaccinating doctors is now running with
'Child and Family' and can subsequently be extended to the entire target group.
PMID- 11004907
TI - [Diabetes mellitus type 1 and associated organ-specific autoimmunity].
AB - Autoimmune type 1 diabetic patients show a high prevalence of thyroid peroxidase
(TPO), parietal cell (PCA), anti-adrenal (AAA) and anti-endomysium antibodies
(EmA-IgA), which may be accompanied with clinical disease. We studied the grade
of associated organ-specific autoimmunity and the pattern of prevalence of TPO
and PCA by age, gender, duration, age at onset of diabetes, and HLA DR haplotype
in 783 type 1 diabetic patients, consisting of 286 children and 497 adults (M/F:
389/394), with a mean diabetes duration of 11.8 +/- 10.1 years. The relationship
between islet cell (ICA), glutamic acid decarboxylase-65 (GADA) and thyro-gastric
auto-antibodies was also investigated. TPO were present in 21.6%, PCA in 18.3%,
AAA in 2.2% and EmA-IgA in 2.1% of the patients. The presence of TPO is
determined by gender (p < 0.0001), age (P = 0.0008), and PCA status (p = 0.029).
The presence of PCA is only influenced by age (p = 0.0027) and TPO status (p =
0.0155). Patients with ICA+ > or = 3 years had a higher prevalence of thyro
gastric auto-antibodies (p = 0.045) than ICA- subjects. Also, PCA were more
prevalent in GADA+ than GADA- patients (p = 0.005). We observed an association
between HLA DR5 and PCA (p = 0.0012). Dysthyroidism was more prevalent in TPO+
than TPO- subjects (p < 0.0001). PCA+ subjects had a higher prevalence of iron
deficiency anaemia (p = 0.0099) and pernicious anaemia (p < 0.0001) than PCA-
patients. In conclusion, particularly type 1 diabetic patients with persisting
ICA > or = 3 years or with GADA, show a high prevalence of thyro-gastric auto
antibodies. Based on antibody-positivity we observed a high prevalence of thyroid
disease, iron deficiency anaemia and pernicious anaemia, which can compromise the
health of the diabetic patient.
PMID- 11004909
TI - [DMW special topic issue: Nephrology].
PMID- 11004908
TI - [Targeting of chlorine E6 by EGF increasing its photodynamic activity in
selective ways].
AB - Certain tumor cells, such as squamous carcinoma cells, express an increased
number of epidermal growth factor (EGF) receptors. The goal of this study was the
targeted delivery of the photocytotoxic compound Sn(IV)chlorine e6
monoethylenediamine++ (SnCe6(ED)) to tumors that overexpress the EGF receptor.
Therefore EGF was conjugated to SnCe6(ED) through a carrier, such as dextran
(Dex) and human serum albumin (HSA), followed by the evaluation of the
photocytotoxicity on the EGF receptor overexpressing MDA-MB-468 cell line. The
photobiologic activity of these conjugates was then compared to a conjugate of
the photosensitizer to HSA or dextran, or to the photosensitizer alone. In
contrast to EGF-HSA-SnCe6(ED), the affinity of EGF for its receptor was
substantially impaired upon conjugation in EGF-Dex-SnCe6(ED). In correlation with
these results, EGF-HSA-SnCe6(ED) displayed a high cytotoxicity (IC50, 63 nM) on
MDA-MB-468 cells at a light dose of 27 kJ/m2, whereas EGF-Dex-SnCe6(ED) showed
very limited photocytotoxicity. In the presence of a competing EGF concentration
(10 microM), EGF-HSA-SnCe6(ED) was not cytotoxic anymore. The high
photocytoxicity of EGF-HSA-SnCe6(ED) was shown to be a result of a high
intracellular concentration in MDA-MB-468 cells, which could be lowered
dramatically by incubating the conjugate with a competing EGF concentration. In
contrast, EGF-Dex-SnCe6(ED) displayed very poor accumulation in MDA-MB-468 cells,
in agreement with its low EGF receptor affinity and photocytoxicity. Besides, it
could be demonstrated that EGF-HSA-SnCe6(ED) produced intracellularly ROS
(reactive oxygen species) upon light irradiation, more than EGF-Dex-SnCe6(ED)
did. It was concluded that, in contrast to EGF-Dex-SnCe6(ED) the photodynamic
activity of the EGF-HSA conjugate of SnCe6(ED) on MDA-MB-468 breast
adenocarcinoma cells is EGF-specific and more potent than free SnCe6(ED).
PMID- 11004910
TI - [Treatment of IGA nephritis].
PMID- 11004911
TI - [Therapy options in systemic AL-amyloidosis with renal involvement].
AB - BACKGROUND AND OBJECTIVE: Despite significant efficacy of melphalan and
prednisone in the therapy of systemic AL(light chain amyloid)amyloidosis the
prognosis of the disease is poor. In patients with severe renal manifestation the
reported results of low-dose melphalan therapy are inconclusive with respect to
relief of clinical symptoms and overall prognosis. PATIENTS AND METHODS: We
report our results of therapy in a group of 22 patients (8 women, 14 men, mean
age 60 years) with renal involvement as the main manifestation of systemic AL
amyloidosis without overt myeloma. RESULTS: Ten patients were treated with low
doses of melphalan and prednisone. No significant clinical improvement was
observed in any case: the patients died an average of 12 months after diagnosis
of the disease. Three patients were treated with high doses of melphalan followed
by autologous stem cell transplantation. One patient died due to septicaemia
after high-dose chemotherapy. Two of the patients experienced significant
remission and live virtually free of clinical symptoms 12 and 18 months after
therapy. Nine patients were treated only symptomatically: four of them were alive
an average of 30 months after diagnosis of systemic AL-amyloidosis. CONCLUSIONS:
Only high-dose melphalan therapy offered a realistic chance of amelioration of
clinical symptoms in our group of patients, although therapy-associated risks
seem to be high. In patients with severe renal amyloidosis, who are not
considered for high-dose therapy, particularly careful consideration of potential
benefits and possible risks of conventional melphalan therapy is necessary,
because the results of this approach are in doubt.
PMID- 11004912
TI - [Hypocomplementemic urticarial vasculitis syndrome].
AB - HISTORY AND ADMISSION FINDINGS: A 40-year-old woman was admitted with recurrent
membranoproliferative glomerulonephritis. For many years she had been suffering
from joint pains and attacks of angio-oedema of the upper and lower lip. Physical
examination was unremarkable except for marked oedema and urticaria of the trunk
and limbs. INVESTIGATIONS: Skin biopsy revealed urticaria with vasculitis.
Complement fractions C3, C4 and C1q were reduced, and C1q antibodies were
demonstrated. DIAGNOSIS, TREATMENT AND COURSE: The findings of urticaria with
vasculitis and reduced complement levels as cardinal symptoms together with joint
pains, glomerulonephritis and C1q antibodies as minor symptoms were diagnostic of
hypocomplementaemic vasculitic urticaria syndrome. The urticaria disappeared
immediately when immunosuppressive treatment with prednisolone and
cyclophosphamide was started, and the nephritic signs regressed. CONCLUSION:
Differentiation of a vasculitic and a non-vasculitic form of chronic urticaria
provides an initial step in delineating the underlying disease. Severe systemic
disease such as collagen disease or vasculitis is not rare in vasculitic
urticaria and requires long-term immunosuppression.
PMID- 11004913
TI - [Early treatment of IgA nephritis is indicated by prognostic factors].
PMID- 11004914
TI - [Treatment of IgA nephropathies: a critical viewpoint].
PMID- 11004915
TI - [Vaccinations and medical recommendations for patients traveling after organ
transplantation].
PMID- 11004916
TI - [Xenotransplantation and social risks].
PMID- 11004917
TI - [Renal artery stenosis].
PMID- 11004918
TI - [Nietzsche's medical legacy. An account on the centennial of his death].
PMID- 11004919
TI - [Emergency admissions of patients with stroke in the Munster area. A cross
sectional study of the quality of regional health care].
PMID- 11004920
TI - [Delivery of hospital discharge reports to contract physicians. I].
PMID- 11004921
TI - [Delivery of hospital discharge reports to contract physicians. II].
PMID- 11004922
TI - [Publishing of negative results in experimental research].
PMID- 11004924
TI - Algorithms: let's give them back.
PMID- 11004923
TI - [Human genome project: medicine in the light of evolution].
PMID- 11004925
TI - Irregular rhythm in a 67-year-old man.
PMID- 11004926
TI - Comprehensive management of type 2 diabetes.
PMID- 11004927
TI - Hysterectomy or an alternative?
PMID- 11004928
TI - Chronic pain: 2. The case for opioids.
PMID- 11004929
TI - A 55-year-old woman with a sore throat.
PMID- 11004930
TI - Antimicrobial prophylaxis in surgery.
PMID- 11004931
TI - Prevention of bacterial endocarditis.
PMID- 11004932
TI - Medical education in the 'postgenomic era'.
AB - The sequence of the human genome is very nearly in hand; the first draft has been
completed, and the finished sequence will be available years ahead of schedule.
Already, advances in medical genetics have affected the day-to-day practice of
medicine by providing more powerful approaches to diagnosis of genetic disorders
and cancer. But the full impact of the integration of genetics into medical
practice lies before us.
PMID- 11004933
TI - The dark side of the digital revolution. How to assess technology for potential
side effects and contraindications.
PMID- 11004934
TI - Menopause and mood. Is depression linked with hormone changes?
AB - For most women, the perimenopause is not associated with depression. In those who
do become depressed, mood symptoms tend to decrease at the end of menopause,
regardless of previous history of depression. Many of the changes in brain
function that affect mood are secondary to changing estrogen levels in the brain.
Treatment with estrogen alone may improve mood in women with mild depressive
symptoms, but those unresponsive to estrogen and women who have moderate to
severe depression need antidepressant therapy.
PMID- 11004935
TI - Weight gain during menopause. Is it inevitable or can it be prevented?
AB - The years surrounding the menopause are associated with weight gain, increased
central adiposity, and decreased physical activity. While weight change occurs
independent of menopausal status, adverse changes in body fat distribution and
body composition may be due to hormonal changes occurring during the menopausal
transition. The one factor most consistently related to weight gain is physical
activity. To avoid weight gain, women should make regular physical activity a
priority. Although HRT use is widely believed to cause weight gain, data from the
PEPI trial do not support this belief. Moreover, HRT may have a protective effect
in reducing central adiposity, although more long-term studies using CT or MRI to
measure visceral fat are needed to confirm this hypothesis. Data from the Women's
Healthy Lifestyle Project provide clear evidence that weight gain and increased
waist circumference, along with elevations in lipid levels and other CHD risk
factors, are preventable through use of lifestyle intervention in healthy
menopausal-aged women. Given the prevalence and chronic course of obesity, weight
gain prevention should be recognized as an important health goal for women before
they approach menopause.
PMID- 11004936
TI - HRT to prevent cardiovascular disease. What studies show, how to advise patients.
AB - How should you advise postmenopausal patients who are considering estrogen
therapy? Do the potential cardiovascular benefits outweigh the risks? Does
hormone therapy improve the cardiovascular risk profile in women with established
coronary artery disease? In this article, Drs Wood and Cox help clarify the
current clinical data for and against hormone replacement therapy for prevention
of cardiovascular disease. In addition, they discuss current treatment
recommendations and future directions in hormone therapy.
PMID- 11004937
TI - Postmenopausal osteoporosis. Strategies for preventing bone loss, avoiding
fracture.
AB - Implementing osteoporosis prevention strategies through lifestyle modification
and pharmacologic treatment reduces patient morbidity and mortality, as well as
the cost to the healthcare system. All women should be advised about their risk
factors and educated about options to reduce the risk. The primary care physician
plays a crucial role in identifying women at risk who are most likely to benefit
from intervention. Treatment decisions should be based on each woman's medical
history and personal preferences. The optimal duration of treatment, especially
with the newer agents, such as the SERMs and bisphosphonates, requires further
investigation.
PMID- 11004938
TI - Beta blockade in patients with congestive heart failure. Why, who, and how.
AB - In patients with CHF, physicians should aim to treat the LV dysfunction, not just
the CHF symptoms. LV dysfunction is a chronic disease that is usually
progressive, even when it seem compensated. The risk of sudden death or
progressive CHF is very real. Adding a beta blocker to the treatment regimen
while the disease is still compensated or after resolution of an acute
exacerbation can stabilize or reverse the LV dysfunction and improve survival.
Beta blockade is now a vital part of the standard of care for most patients with
LV dysfunction.
PMID- 11004940
TI - Genetics beyond Mendel. Understanding nontraditional inheritance patterns.
AB - Many medical conditions that clearly have a strong genetic component are not
transmitted in a straightforward dominant, recessive, or X-linked pattern. Recent
progress in understanding other modes of inheritance, such as imprinting,
trinucleotide repeat expansion, mitochondrial inheritance, and mosaicism, has
allowed us to solve many of these hereditary puzzles. Such advances have led to
improvements in diagnosis and genetic counseling for patients affected with these
disorders and should be valuable in development of effective therapies for some
of these disorders in the future.
PMID- 11004939
TI - Providing relief from headache pain. Current options for acute and prophylactic
therapy.
AB - The sometimes debilitating pain of migraine and other types of primary headache
can be difficult to control with acute drug therapy alone. Often patients need
both acute and prophylactic treatment to keep headache pain at bay. Dr Ward
discusses the current treatment options for migraine with and without aura,
tension-type headache, and cluster headache. He also provides practical pointers
for use of the various formulations of specific drugs, including the newer
"triptan" medications.
PMID- 11004941
TI - Gallstones, from gallbladder to gut. Management options for diverse
complications.
AB - Gallstones may be incidental and asymptomatic or painful and accompanied by life
threatening obstruction or infection. A thorough knowledge of potential
complications is therefore critical, especially because some asymptomatic stones
require prompt treatment. In this article, Drs Agrawal and Jonnalagadda provide
valuable instructions for recognizing and treating the various manifestations of
gallstone disease.
PMID- 11004942
TI - The enlarging pearly nodule. Palisaded encapsulated neuroma.
PMID- 11004943
TI - Menopause and mood.
PMID- 11004944
TI - Darwin's beautiful notion: sexual selection and the plurality of moral codes.
AB - One of the explicit objectives of Darwin's Descent of Man, and Selection in
Relation to Sex was to explain cultural differences seen in human beings. Such an
explanation, Darwin believed, was to rest upon an understanding of sexual
selection. I examine the role that the beautiful plays within the mechanism of
sexual selection as it works to differentiate isolated groups. It is suggested
that an examination of the relationship between sexual selection and artificial
selection--a relationship mediated by the beautiful--will illuminate key issues
of the Descent as well as contemporary debates regarding the relationship between
evolution and ethics. The beautiful, originally rooted in sexual selection, can
become de-coupled from sexual selection and utilized in some selective process
which is conscious.
PMID- 11004945
TI - Darwin's species category realism.
AB - Ever since Charles Darwin's On the Origin of Species was published, the received
view has been that Darwin literally thought of species as not extra-mentally
real. In 1969 Michael Ghiselin upset the received view by interpreting Darwin to
mean that species taxa are indeed real but not the species category. In 1985 John
Beatty took Ghiselin's thesis a step further by providing a strategy theory to
explain why Darwin would say one thing (his repeated nominalistic definition of
species) and do another (hold that species taxa are real). In the present paper I
attempt to take this line of interpretation to a new level. Guided by the
principle of charity, I provide and analyze a considerable amount of evidence
from Darwin's mature writings (both private and published) to show that (contra
Ghiselin and Beatty) Darwin did not simply accept the species delimitations of
his fellow naturalists but actually employed, repeatedly and consistently, a
species concept in a thoroughly modern sense, albeit with an implicit definition,
a concept uniquely his own and fully in accord with his theory of evolution by
natural selection. This implicit concept and definition is carefully
reconstructed in the present paper. A new strategy theory is then provided to
account for why Darwin would define species (both taxa and category)
nominalistically on the one hand but delimit species realistically on the other.
PMID- 11004946
TI - The evolution of complexity. Essay review.
PMID- 11004947
TI - [Gastrointestinal metastases of lobular mammary carcinoma].
AB - Three women, two aged 63 and one aged 47 years, developed serious abdominal pains
and nausea during and/or years after treatment for metastasized lobular mammary
carcinoma. These symptoms were due to jejunal tumour with perforation, sigmoid
and hepatic metastases and perforated gastric metastases, respectively. After
surgical treatment of the affected part of the gastrointestinal tract, the
patients survived for a number of months without abdominal symptoms. Infiltrating
lobular mammary carcinoma is more often associated with gastrointestinal
metastases than infiltrating ductal mammary carcinoma. Progressive abdominal
symptoms attributable to such metastases constitute an indication for a change of
the systemic treatment. In case of insufficient effect of this treatment, and in
acute situations, surgical treatment may result in protracted palliation.
PMID- 11004949
TI - [Immunology in the medical practice. XXXIII. Hereditary immune deficiencies: from
genotype to phenotype].
AB - The advances of molecular biological techniques of the last decade have made
possible identification of a rapidly increasing number of congenital (or primary)
immune deficiencies at the genetic level. As soon as an immune deficiency is
becoming a likely conclusion from a series of diagnostic laboratory tests, these
recent developments in molecular techniques allow us in principle to make a
conclusive diagnosis on the basis of a well-defined genetic defect. The
hereditary immune deficiencies can be divided in 4 groups according to the
functional immune aberration: antigen recognition, communication between immune
cells, adhesion and directional motility, and killing as an effector mechanism.
PMID- 11004948
TI - [Carrier state of x-linked adrenoleukodystrophy].
AB - X-linked adrenoleukodystrophy (X-ALD) is a sex-linked, inherited, metabolic
disorder affecting the nervous system and endocrine organs. At least 20 to 50% of
female carriers develop neurological deficits. Identification of female carriers
is important, among other reasons because unnecessary new cases of this disorder,
which is frequently lethal in boys, can be prevented by prenatal diagnosis.
Furthermore, affected male offspring can be screened for adrenocortical
insufficiency, which is treatable, or for early signs of cerebral involvement in
which case bone marrow transplantation may be considered. Whether or not someone
is a carrier can be investigated by determining the concentrations of saturated
very-long-chain fatty acids in the plasma or cultured skin fibroblasts, by
looking for the presence of X-ALD protein in cultured fibroblasts and by carrying
out mutation analysis. Spasticity, painful muscular cramps, lumbago and
arthralgias can be treated symptomatically with the same agents used for other
aetiologies. A clinical geneticist can provide advice on heredity and the
possibilities of prenatal diagnosis and pre-implantation techniques.
PMID- 11004950
TI - [Pharmacotherapeutic compass 2000/2001].
AB - The Commission Pharmaceutical Help of the Health Care Insurance Board uses the
Pharmacotherapeutical compass to inform the medical profession annually about
medical drugs. In the 2000/2001 edition the most important alterations are
changes in the introductions of: antidepressants, medicines for peptic disorders,
medicines for rheumatoid arthritis and osteoarthritis, haematopoietic growth
factors, anticonvulsants, medicines for Parkinson, medicines for congestive heart
failure, antiretroviral medicines, medicines for osteoporosis, short acting
insuline-analogues and oral antihyperglycaemics. The introductions about Horton's
neuralgia and erectile dysfunction are new. For some (new) medicines
recommendations are made, for the antidepressants and medicines for peptic
disorders some recommendations have been changed.
PMID- 11004951
TI - [Diagnostic image (2). (Gas gangrene of diabetic foot)].
AB - A 63-year-old woman with diabetes mellitus type 2 and an ulcer on the foot
developed gas gangrene and was treated with antibiotics and surgical excision.
She died before she could be treated with hyperbaric oxygen.
PMID- 11004952
TI - [Increased proportion of elementary school children with asthmatic symptoms in
the Netherlands, 1984/85-1994/95; a literature review].
AB - OBJECTIVE: To investigate whether the prevalence of asthmatic symptoms among
children in the Netherlands has changed. DESIGN: Literature study. METHOD:
Investigations into the prevalence of children with asthmatic symptoms were
collected from Medline, Embase and various libraries if they had been performed
between 1984/'85 and 1994/'95 and had used the so-called WHO or Region list. 23
studies were selected with data on 76,353 elementary school pupils. Linear
regression analysis, weighed for the number of children, was used to determine if
the proportions of children with asthmatic symptoms had increased over the years.
RESULTS: In 10 years the prevalence of recent shortness of breath had increased
by 107% (from 4.16 to 8.63%), that of recent wheeze by 16% (from 10.64 to
12.35%), that of recent attacks of breathlessness with wheezing by 17% (from 5.29
to 6.19%), and for chronic cough by 259 (from 1.05 to 3.77%) to 272% (from 3.14
to 11.68%). The prevalence of doctor-diagnosed asthma had increased by 120% (from
2.82 to 6.19%). CONCLUSION: There had been a pronounced increase in the
percentage of primary schoolchildren with asthmatic symptoms between 1984/'85 and
1994/'95. The prevalence of doctor-diagnosed asthma increased faster then did key
symptoms of asthma.
PMID- 11004953
TI - [Relation between ethnicity and reason for referral of new patients to the
Internal Medicine outpatient clinic of the Academic Hospital Rotterdam-Dijkzigt,
1997].
AB - OBJECTIVE: To inventory the ethnic composition of the patients referred to an
internal medicine outpatient clinic of a Dutch academic hospital and to determine
to what extent ethnic minorities differ from Dutch patients in terms of referral
reasons, taking relevant background characteristics into account. DESIGN: Cross
sectional analysis. METHOD: Data were collected on all new patients referred in
1997 for the first time to the internal medicine outpatient clinic of the
Academic Hospital Dijkzigt, Rotterdam, the Netherlands, using the hospital
information system (n = 3205). Patients were categorised into ethnic groups based
on country of birth or name. Ethnic differences in referral reasons were tested
for the 4 largest ethnic groups by means of logistic regression analysis with
adjustment for age, sex, mean income of the zipcode area of the patients'
residence and type of health insurance. RESULTS: The percentage of ethnic
minorities amongst all referred patients was 22% (696/3205). The percentage of
ethnic minorities among the patients referred from the catchment area of the
outpatient clinic was 48% (209/440). Compared with Dutch patients Turkish
patients were referred more often with stomach ache (odds ratio (OR): 4.26) and
joint problems (OR: 7.16) as reasons. Moroccans were more often referred with
stomach ache (OR: 4.10) and diabetes (OR: 4.51). Ethnic minorities were referred
less often with dyslipidemia (Turks: OR: 0.11; Surinamese: OR: 0.17; Moroccans: 0
patients).
PMID- 11004954
TI - [Cyanosis and cirrhosis of liver: hepatopulmonary syndrome].
AB - A 66-year-old man with Child-B alcoholic cirrhosis presented with melaena due to
hemorrhagic gastritis. Clinical examination revealed cyanosis and clubbing
accompanied by severe hypoxaemia without signs of obstructive or restrictive lung
disease. Contrast-enhanced echocardiography showed right to left shunt due to
intrapulmonary shunting leading to the diagnosis of hepatopulmonary syndrome.
Hypoxaemia in patients suffering from chronic liver disease can have different
causes but in the presence of cyanosis and clubbing without signs of lung disease
the hepatopulmonary syndrome should be suspected. When presence of intrapulmonary
shunts has been proven by contrast-enhanced echocardiography, a 100% oxygen test
can determine the need for pulmonary angiography and thus determine the
indication for interventional therapy or liver transplantation. The patient
described was treated supportively with long-term oxygen therapy 6 l/min. Three
months later his clinical condition was stable. An attempt to reduce the need for
nasal oxygen failed.
PMID- 11004955
TI - [Complementary therapies in the hospital:'if you can't beat them, join them'?].
AB - Some major cancer hospitals in the United States have established a department
for complementary medicine as a service to their patients. Surveys in the
Netherlands have shown that notably nursing staff and consumers consider the
availability of complementary therapy in health care to be very important.
Nevertheless, this appears to be an undesirable development as the effectiveness
of these therapies has not been demonstrated and the therapists involved might
interfere with regular patient therapy.
PMID- 11004956
TI - [Publishing in biomedical journals in the year 2000 and after; report of a
symposium].
AB - On the occasion of the oration by prof. dr. A.J.P.M. Overbeke, executive editor
of the Nederlands Tijdschrift voor Geneeskunde, a symposium was organized on 16
June 2000. The lecturers were (chief) editors of medical journals. Many changes
in medical publishing are to be expected in the next 10 years. The new technology
will play an important part in this, but the details remain to be seen.
Scientific journals can continue to exist in the electronic era if they produce
legible, i.e. brief and clear articles in the printed version and offer extra
information on the internet: details of methods used and statistical analyses and
extensive tables. Also, the contributions of the various authors are printed. Not
all, but only a few authors should make certain that the work described has
indeed been performed and these would be responsible for the contents of the
entire article. It appeared that the main part played by physicians in mass media
is that of occasional informants. There still exist possibilities to use the
media in distributing and supporting the messages of medicine and in elucidating
the dilemmas. While 'archivist' journals mostly record scientific work presented,
the task of the 'newspaper journals' consists of informing, interpreting,
criticizing and stimulating. In this 'colouring' of the contents of the journal,
the independence of the chief editors is of great importance. The innovations in
medicine of the past century appear to be based mostly on the work of
predecessors, of research physicians opposing established authorities, and on
coincidence. The interval between discovery and publication has grown much
shorter.
PMID- 11004957
TI - [Familial hypercholesterolemia: recognition and prevention of cardiac
complications at a young age].
PMID- 11004958
TI - Building teams, synergy, and your resources.
PMID- 11004959
TI - Treating glaucoma.
PMID- 11004960
TI - Deep brain stimulation for advanced Parkinson's disease.
AB - Deep brain stimulation (DBS) is a new and promising technique for the treatment
of movement disorders. Medically intractable Parkinson's disease (PD) is one of
the most common indications for DBS. There are three possible subcortical targets
for PD, depending on the symptomatology (i.e., the motor subdivision of the
thalamus, the globus pallidus internus, the subthalamic nucleus [STN]). Thalamic
stimulation has been well established as a safe and effective treatment for
essential tremor and the tremor associated with PD. Globus pallidus internus and
STN DBS are being investigated for the treatment of all the cardinal signs of PD.
This article describes the pathophysiology of PD, the surgical treatment history
of PD, surgical techniques used for DBS implants, and the role the perioperative
nurse has in the care of the patients undergoing these procedures.
PMID- 11004961
TI - Chronic regional pain syndrome, type 1: Part I.
AB - Chronic regional pain syndrome refers to a class of disorders thought to involve
common neuropathic and clinical features. These disorders usually are caused by
injury, and they manifest in pain and sensory changes that are disproportionate
in intensity, distribution, and duration to the underlying pathology. The result
of these injuries is significant impairment of motor function over time. This
article is divided into two parts. Part I discusses background information such
as pain, pathophysiology, diagnosis, clinical stages, and the most common
treatment modality, sympathetic nerve blocks. Part II, discusses alternate
treatment modalities, such as sympathectomy, physical therapy, stimulators,
trigger point injections, acupuncture, tourniquet effects, placebo effects, and
amputation.
PMID- 11004962
TI - Reducing percutaneous injuries in the OR by educational methods.
AB - Exposure to bloodborne pathogens (e.g., HIV, hepatitis B, hepatitis C) through
percutaneous injuries is an occupational risk for health care workers, especially
those in the OR. The incidence of disease continues to rise, although
occupational exposures often go unreported. Percutaneous injury prevention
methods have included use of safety devices, practice changes, and educational
programs. An educational intervention to increase awareness of risk, provide
suggestions for injury reduction, and encourage reporting of exposures was
performed at a university teaching hospital. Preliminary qualitative results show
increased exposure reporting, increased use of personal protective equipment, and
increased awareness of disease exposure risk among OR personnel.
PMID- 11004963
TI - Perioperative nursing and animal-assisted therapy.
AB - Interacting with animals has been shown to reduce blood pressure and cholesterol,
decrease anxiety, and improve a person's sense of well being. Animal-assisted
therapy (AAT) can be incorporated into the care of perioperative patients. Some
of the goals that can be met by using trained and certified therapy animals are
reducing stress preoperatively, motivating patients to have a positive attitude,
promoting postoperative activity, and reducing the need for pain medication.
Infection control, immunosuppressed patients, and research are issues regarding
AAT in the hospital setting that must be covered by policy and procedure.
Suggestions for setting up an AAT program are discussed.
PMID- 11004964
TI - The art of fitting into our lives.
AB - When there is a long-standing disparity between our reality and goals, internal
friction grows unchecked. The incongruency of being out of step with ourselves
creates major stress. Achieving congruency in our lives leads to personal and
professional success. The process of achieving congruency brings us closer to our
life goals, and it necessarily entails self-examination and insight. We must
examine our likes, dislikes, strengths, weaknesses, and desires and set realistic
and specific goals. By aligning our words and actions to match our goals, we are
more likely to achieve those goals and begin fitting into the lives we want to
lead.
PMID- 11004965
TI - Storytelling can be a valuable teaching aid.
PMID- 11004966
TI - [ELAN study].
PMID- 11004967
TI - [Characteristics of a cohort of 4,000 French patients with angina. The ELAN
study].
AB - The ELAN (Etude Longitudinale dans l'ANgor) study was carried out to evaluate
factors influencing the occurrence of death, myocardial infarction and
revascularization procedures in patients with known angina pectoris. Analysis of
baseline data collected in January 1997 involves 4,035 patients throughout
France, which were recruited by 613 cardiologists practising on a private,
hospital or mixed basis. The study population comprised 75% of men with a mean
age of 65 years and 25% of women with a mean age of 70 years. Eighty eight
percent of the patients had at least one cardiovascular risk factor, and nearly
half of them had two or more factors; hypercholesterolemia and hypertension were
the two most frequent ones. Reported cardiovascular past events included
myocardial infarction in 47% of patients, PTCA in 33% and aorto-coronary bypass
in 24%. Angina pectoris had been diagnosed within the previous year in 39% of
patients. Exertional angina was the most common type (66%), with grade I/II
angina being most frequently found (more than 70% of all cases). Management
strategies are especially described for angina patients diagnosed within the
previous year. More than half of the patients had undergone exercise testing
within the previous 12 months, while scanning and coronary arteriography had been
performed in 15% and 72%, respectively. Ninety five percent of patients were
under antianginal drug therapy, with combined therapies being used in 58% of
them. The most frequently prescribed drugs were betablockers (63%) and nitrates
(53%). In 74% of patients, aspirin was given in addition to conventional
antianginal agents. These data will be reviewed in a one-year cohort analysis as
potential predictive factors for the occurrence of cardiovascular events.
PMID- 11004968
TI - [One-year follow-up of a population of patients with angina. Factors influencing
mortality and occurrence of cardiovascular events. Results of the ELAN study].
AB - The ELAN (Etude longitudinale dans l'angor) study was carried out both to acquire
better knowledge of the occurrence of major cardiovascular events (myocardial
infarction, revascularization surgery, death) in patients followed up for angina
pectoris, and to determine the factors influencing such events. A cohort of
angina patients was formed in January 1997, and 3,284 patients were followed up
by 488 French cardiologists during a one-year period. Of these 3,284 patients, 96
(29/1000) died; causes of death included underlying coronary heart disease in 31,
sudden death in 8, other cardiac aetiologies in 35, and noncardiac causes in 22.
Sixty-nine (21/1000) patients developed myocardial infarction, 240 (73/1000)
underwent PTCA, and 119 (36/1000) underwent coronary bypass surgery. Factors
associated with an increased risk of death were age, diabetes mellitus, heart
failure and angina type, mixed and rest angina being associated with poorer
prognosis compared to exertional angina. Infarction risk increased with age and a
history of previous infarction. Analysis of therapeutic factors after adjustment
for the above risk factors showed a beneficial effect of betablockers on both
cardiovascular and all-cause mortality and of aspirin on all-cause mortality.
PMID- 11004969
TI - [Percutaneous angioplasty of unprotected left main coronary disease with
implantation of systematic stenting. Immediate and mid-term results].
AB - The authors report the immediate and medium term results of percutaneous
angioplasty of unprotected left main coronary disease with systematic stenting.
Between March 1994 and December 1998, out of 6,006 patients undergoing coronary
angioplasty, 92 had significant unprotected left main stem disease. The majority
of patients was male (74 men, 80%) with an average age of 74.3 +/- 8.1 years.
Between March 1994 and October 1996, only patients with a surgical
contraindication were treated by angioplasty (n = 39). After October 1996, the
indications were extended to patients who did not have surgical contraindications
(n = 53). During the hospital phase, 4 patients (4%) died (ventricular
arrhythmia: 1, cardiogenic shock: 2, gastro-intestinal haemorrhage: 1). No non
fatal infarction with or without Q waves were observed, and no emergency coronary
bypass surgical procedures were required. The angiographic success rate was 100%.
During follow-up (7.3 +/- 5.8 months), 6 other patients died, 13 required a
repeat coronary angioplasty, 4 for restenosis of the left main coronary artery,
and 2 underwent coronary bypass surgery. The actuarial survival rate was 89 +/-
5% at 1 year and 85 +/- 17% at 3 years. Percutaneous angioplasty for unprotected
left main coronary disease with systematic stenting was performed with acceptable
hospital and medium term results.
PMID- 11004970
TI - [Coronary stents in patients with severe left ventricular dysfunction. Hospital
and long-term results].
AB - The aim of this study was to evaluate the risks and benefits, immediate and at
long term, of coronary angioplasty associated with stent implantation in patients
with severe left ventricular dysfunction. It was a retrospective study in which
all patients with left ventricular ejection fractions 35% who underwent
angioplasty between December 1994 and January 1998 were included. Seventy eight
patients with an average ejection fraction of 29 +/- 6% who were haemodynamically
stable were retained, excluding acute myocardial infarctions and cases of
cardiogenic shock. The population was mainly masculine (6(men and 13 women) with
a mean age of 65 +/- 11 years. The primary success rate was 97%. The loss of a
collateral branch during the procedure, causing a non-Q wave infarction and the
impossibility of implanting the stent at the desired site in another patient,
were the only two failures. Hospital mortality was nil. The mean follow-up period
was 450 +/- 290 days; long-term mortality was 17%. All deaths were of
cardiovascular origin. The probability of survival at 6 months, 1 year and 800
days, was 88, 85 and 75% respectively. The good initial results were not
maintained at long-term, but this could not be attributed to restenosis or to the
pre-existing left ventricular dysfunction.
PMID- 11004971
TI - [Cardiac abnormalities in a prospective series of 40 patients with type 2
diabetes].
AB - Cardiovascular mortality, the principal cause of early death in diabetics, is
multifactorial. A prospective study was undertaken to analyse the different
factors of excess cardiac complications in 40 patients with type 2 diabetes,
whatever the symptomatology, by making an inventory of the cardiac abnormalities
(systolic and diastolic left ventricular function, left ventricular hypertrophy,
abnormalities of myocardial perfusion, heart rate variability and arrhythmias).
Patients underwent 24 hour Holter monitoring, high amplification signal averaged
electrocardiography, echocardiography, Thallium scintigraphy with a dipyridamole
test followed by coronary angiography when positive. Patients were aged 60 +/- 8
years, diabetics for 11.8 +/- 6.8 years, and had associated cardiovascular risk
factors: 85% were obese, 75% were hypertensive, 62.5% had hypercholesterolaemia
and 60% were smokers. The HbA1C was 9.2 +/- 19%. An increased left ventricular
mass was observed in 34.2% of patients. The left ventricular ejection fraction
was normal (59.1 +/- 6.8%); 69.7% of patients had left ventricular diastolic
dysfunction. Reduced heart rate variability was observed in 51.8% of cases. Late
ventricular potentials were recorded on high amplification signal averaging in
39.5% of patients; 25.6% had significant ventricular extrasystoles and 52.2% had
atrial extrasystoles. Twelve patients (45%) underwent Thallium myocardial
scintigraphy with a positive dipyridamole test, 8 of whom had coronary lesions on
angiography. The excess cardiac complications of diabetes is mainly due to
ischaemic heart disease aggravated by autonomic neuropathy, left ventricular
diastolic dysfunction, arrhythmias and left ventricular hypertrophy. In future,
larger series are required to demonstrate that this detection can guide
therapeutic intervention and reduce cardiac morbidity and mortality of diabetics.
PMID- 11004972
TI - [Specific factors of diabetes in the rehabilitation of coronary patients].
AB - This prospective controlled trial included two groups of subjects with coronary
artery disease: one of 33 patients with non-insulin-dependent diabetes mellitus
(6 females and 27 males, mean age 57 +/- 9 years, left ventricular ejection
fraction of 56 +/- 14%) and the control group of 33 subjects without diabetes (3
females and 33 males, mean age of 57 +/- 11 years, LVEF of 58 +/- 11%). Before
training heart rate was faster for patients with diabetes at rest (72 +/- 11 vs
66 +/- 81 bpm, p = 0.03) and at the end of the stress test (127 +/- 15 versus 118
+/- 18 bpm, p = 0.03). After rehabilitation, resting heart rate and peak heart
rate were similar. However cardiovascular capacities improvement was better in
subjects without diabetes mellitus, especially concerning peak VO2 (28.98 +/-
8.88 versus 22.78 +/- 6.28 mL/min/kg, p < 0.01) and mechanical power (138 +/- 48
versus 118 +/- 23 watts, p < 0.01). Two groups were retrospectively distinguished
among diabetic patients: one group of 17 patients showing a VO2 improvement
superior to 5% and a second group non improved (VO2 < 5%). For the second group
the two selective factors were higher fasting glycemia (1.83 +/- 0.75 versus 1.31
+/- 0.38 g/L, p = 0.01) and higher hemoglobin A1C (8.05 +/- 2.04 vs 6.62 +/-
1.03%, p = 0.02). Heart rate variability was not significantly different for
these two groups: changes in autonomic nervous system cannot explain resistance
of diabetic subjects to training. On the other hand, principal aim must be the
equilibrium of glycemia in the management of diabetes.
PMID- 11004973
TI - [Action of sotalol on high-amplification electrocardiogram].
AB - D,l sotalol is an antiarrhythmic widely used for treating ventricular
excitability, especially ventricular tachycardia (VT). The means of assessing its
efficacy is 24 hour Holter monitoring and programmed ventricular stimulation.
High amplification ECG has also been proposed for predicting the effects of the
drug on the induction of VT. The aim of this study was to assess the results of
high amplification ECG before and after taking sotalol and to compare them with
those of programmed ventricular stimulation. This study was performed in 24
patients with spontaneous and inductible ventricular tachycardia due to ischaemic
heart disease. The two investigations were performed under basal conditions and
after treatment with 160 to 320 mg/day of d,l-sotalol for 8 days. Nine patients
had VT which could not be induced after treatment. In the other 15 cases, the VT
remained inducible and was not significantly slowed. Analysis of different
parameters of high amplification ECG, the QRS duration, RMS 40 and LAS did not
show any difference after treatment in cases with inducible VT or VT suppressed
by treatment. In conclusion, d,l sotalol, even at antiarrhythmic doses, does not
seem to change the parameters of high amplification ECG, and it is therefore not
necessary to stop treatment to carry out this investigation. Moreover, it was
impossible to predict the effect of d,l sotalol on VT by high amplification ECG.
PMID- 11004974
TI - [Use of echocardiography in the diagnosis of carcinoid tumors. Report of 4
cases].
AB - Carcinoid tumours are the most common neuro-endocrine tumours but cardiac
involvement is rarely symptomatic although often observed at post-mortem and
rarely revelatory of the disease. The authors report 4 cases in which
echocardiographic detection of characteristic right ventricular involvement led
to the confirmation of the diagnosis of carcinoid tumour leading to the secondary
diagnosis of the primary carcinoid tumour. The clinical, physiopathological
echocardiographic and therapeutic characteristics of this condition are
discussed.
PMID- 11004975
TI - [Paralysing hypokalemic thyrotoxicosis].
AB - Thyrotoxicosis is a rare cause of hypokalaemia. The clinical presentation
associates signs of thyrotoxicosis which may be discrete, with severe
hypokalaemia and peripheral muscular weakness with paralysis of the lower limbs.
It is important not to miss this diagnosis because of the therapeutic
implications. Treatment of this form of hypokalaemia is that of hyperthyroidism.
PMID- 11004976
TI - [Chronic ischemic left ventricular dysfunction: myocardial hibernation?].
AB - Hibernating myocardium is a term which covers chronic ischaemic left ventricular
dysfunction which is potentially reversible after revascularisation. Hibernating
myocardium is classically associated with chronic hypoperfusion responsible for
hypocontraction and cellular degeneration. This "classical" conception has been
questioned as some workers emphasise that the reduction in coronary reserve
responsible for repeated episodes of ischaemia and stunning could be the main
causes of myocardial dysfunction. Position emission tomography (PET), and, most
of all, myocardial scintigraphy and dobutamine echocardiography are the most
commonly used techniques for detecting hibernating myocardium. Their sensitivity
is good but the specificity and positive predictive value of dobutamine
echocardiography seems to be better than the isotopic techniques. Structural
abnormalities of hibernating myocardium and the delay, which is often long,
between revascularisation and improvement, may explain some of the discordances
between these techniques. Irrespective of the term used, hibernation or chronic
ischaemic left ventricular dysfunction with myocardial viability, the reported
data is in favour of coronary revascularisation with improved long-term quality
of life and reduced mortality in patients with positive viability tests.
PMID- 11004977
TI - [Tissue characterization by study of myocardial response to ultrasound. Review of
the literature and perspectives].
AB - Echocardiography is a routine daily cardiological investigation. Recent
technological developments suggest that it may become possible to quantify
myocardial texture and thereby achieve histological and functional definitions of
cardiac diseases. Two approaches are under evaluation: "videodensitometry" uses
tools of statistical quantification from the echocardiographic image; more
recently, analysis of the radiofrequency signal has been proposed. This is based
on direct exploitation of a continuous signal at the transducer head of wide
dynamic range containing all the information received by the piezo-electric
crystals. These two approaches have given encouraging preliminary results in the
recognition of different myocardial hypertrophic reactions, in diabetic cardiac
disease and in the identification of myocardial viability. Despite the many
remaining problems, the perspectives are promising and a new field of
echocardiography should see the light of day.
PMID- 11004978
TI - [Legionella myopericarditis].
AB - Cardiac involvement in legionella infection is rare but it is the most common
extra-pulmonary complication. It usually takes the form of pericarditis, but a
case of legionella myoparicarditis with global left ventricular hypokinesia on
echocardiography has been described. The authors report a case of myopericarditis
with massive pulmonary oedema and respiratory distress which regressed clinically
and on echocardiography with reduction in chamber dilatation and complete
recovery of left ventricular function. Legionellosis was confirmed on serology.
The infection was probably contracted during a previous hospital admission,
therefore, probably a nosocomial infection. Following the description of this
case, a review of the literature is proposed.
PMID- 11004979
TI - [Partial tricuspid homograft: a new technique for tricuspid valve repair. Report
of a case].
AB - The authors report the case of a drug abuser treated successfully for fungal
tricuspid endocarditis complicated by massive pulmonary embolism. Partial
valvular replacement with a segment of a tricuspid homograft associated with
disobliteration of a pulmonary artery was performed. Peroperative
transoesophageal echocardiography showed satisfactory tricuspid valve function.
The postoperative course was uneventful. After 5 months' follow-up, the patient
was asymptomatic and in good general condition. Control echocardiography showed a
stable operative result.
PMID- 11004980
TI - [Valvular tumor: diagnostic trap. Report of a case of marastic endocarditis].
AB - Marastic endocarditis is a rare clinical condition described in cases of cancer
or other severe inflammatory diseases. The authors report the case of a young
patient in good general condition, admitted after a cerebro-vascular accident.
Investigations showed an isolated mitral valvular mass on transoesophageal
echocardiography which, after unsuccessful medical therapy, was operated. It was,
in fact, a case of marastic endocarditis, and a pulmonary tumour was discovered
one month after surgery. The bronchopulmonary adenocarcinoma had remained
infraclinical beforehand. The advances in echocardiographic imaging will probably
lead to an increase in such cases of early diagnosed thrombotic non-bacterial
endocarditis (ETNB. This case suggests that it is justified to carry out an
aetiological investigation of thrombotic non-bacterial endocarditis in all cases
of isolated mitral valve masses.
PMID- 11004981
TI - [Closure of the Aquitaine days of the French Society of Cardiology].
PMID- 11004982
TI - [Implications of latex allergy].
PMID- 11004983
TI - [Value of transthoracic aspiration puncture in the etiologic diagnosis of
nosocomial pneumonia in patients not admitted to the ICU].
AB - The aim of this study was to determine the etiologic diagnosis of nosocomial
pneumonia in hospitalized patients outside the intensive care unit. The study was
carried out prospectively at the University Hospital Arnau de Vilanova in Lerida
(Spain) from 1 May 1994 through 28 February 1996, during which 103 cases were
diagnosed. Transthoracic needle aspiration (TNA) was chosen as the most useful
diagnostic procedure, given its high specificity and low rate of complications.
Sixty-seven TNA procedures were carried out; 10 (14.9%) were positive. Sputum was
cultured for 62 patients and true positives were observed in 6 (9.7%). Pleural
liquid was cultured for 35 patients and germs were isolated for 2 (5.7%).
Bronchial brushing with a telescoping catheter was performed in 4 patients and
brush culture provided 2 additional positives. Blood samples from 51 patients
were cultured provided 4 additional diagnoses (7.8%). The most commonly found
germs were P. aeruginosa (13.33%), S. aureus (13.3%), C. pneumoniae (10%) and L.
pneumophila (10%). Disease was polymicrobial in 33.3%. Complications were
observed, in the form of pneumothorax, in 2 cases (3%), one of which required
drainage. We conclude that TNA, which is highly specific and has a low rate of
complication, is a useful procedure for diagnosing nosocomial pneumonia in
patients who are not being mechanically ventilated.
PMID- 11004984
TI - [Assessment of excessive day-time sleepiness in professional drivers with
suspected obstructive sleep apnea syndrome].
AB - Excessive daytime sleepiness is a common symptom of obstructive sleep apnea
syndrome (OSAS) and can be a cause of traffic accidents, creating a problem of
particular importance for professional drivers given the associated death,
disability and professional repercussions. We assessed whether the Epworth
sleepiness scale (ESS), which is a subjective measure of daytime sleepiness,
correlates well with multiple sleep latency (MSL) testing, which gives an
objective measure of daytime sleepiness. We also compared each method with the
results of polysomnography (apnea-hypopnea index, arousal index and minimum
oxygen saturation). We studied 55 professional drivers suspected of OSAS. All
answered the ESS questionnaire and underwent polysomnographic and MSL testing. We
found a significant, though not relevant, correlation between the degree of
excessive daytime sleepiness estimated by the ESS and by MSL testing (r = -0.41;
p = 0.002). A significant, though weak, correlation was found between the ESS
score and the arousal index (r = 0.26; p < 0.05). Our results do not clarify
which method is best for measuring excessive daytime sleepiness in professional
drivers suspected of OSAS.
PMID- 11004985
TI - [Usefulness of the IUATLD respiratory symptoms questionnaire for the differential
diagnosis of bronchial asthma and chronic bronchitis].
AB - Our objective was to determine the diagnostic value of the questionnaire devised
by the International Union against Tuberculosis and Lung Disease (IUATLD) for
distinguishing between bronchial asthma and chronic bronchitis. We therefore
compared clinical diagnoses established independently by two pneumologists for
211 patients to the patients' responses to the IUATLD questionnaire. The
questions were analyzed for their ability to discriminate using the responses as
independent variables and the diagnosis as the dependent variable. The individual
predictive capacity of each question and the discriminating functions that
identified the best clusters of questions were calculated using bayesian
analysis. Finally, we compared IUATLD results to tests that assessed lung
function (spirometry), obstruction variability (bronchodilator test, peak flow,
bronchial challenge test), atopy (prick test, serum IgE), and clinical and
biological markers (eosinophilia). The questionnaire correctly diagnosed 91% of
the patients and a cluster of five questions registered a sensitivity of 85.6%,
specificity of 91.4%, a positive predictive value of 93.1% and a negative
predictive value of 82.2%, thus proving superior to the other tests. These
results, along with the ease of administering the questionnaire allows us to
consider the IUATLD instrument to be a good tool for the differential diagnosis
of bronchial asthma and chronic bronchitis.
PMID- 11004986
TI - [Morphometric assessment of rat lungs insufflated with liquid fixative at
different pressures close to total lung capacity].
AB - INTRODUCTION: Liquid lung fixing through the trachea to a pressure of 25 cmH2O is
currently accepted to be ideal. However, some studies do not seem to confirm that
assumption. MATERIAL AND METHODS: The lungs of Fischer rats were filled with
fixing liquid to four different pressures: 20 cm, 25 cm, 30 cm and 35 cmH2O. The
fixed lungs were processed for inspection under a light microscope for
morphometric study. The following variables were recorded: lung volume, tissue
volume, air volume, internal alveolar surface (IAS), alveolar chord to measure
the size of the distal air space, and the number of alveoli. Statistical
comparisons were performed. RESULTS: Lung volume increased with insufflation
pressure, with significant differences related to pressure increases from 20 cm
to 25 cm and from 30 cm to 35 cmH2O. Air volume did not change, although tissue
volume changed when pressure increased from 20 cm to 30 cmH2O and from 30 cm to
35 cmH2O. The increase of tissue volume was related to extravasation of
interstitial fixer. The number of alveoli increased with pressure from 20 to 30
cm and from 30 to 35 cmH2O. IAS increased with pressure from 20 cm and all the
other pressures. Alveolar chord, which is related to size of alveoli, decreased
significantly as pressure increased from 20 cm to 25 cm. CONCLUSION: A pressure
of 25 cmH2O is ideal for liquid fixing of lung volumes. With lower pressures the
lung is partially distended and with higher pressures the fluid can pass into the
interstitial space.
PMID- 11004987
TI - [Assessment of mediastinal tumor involvement (T factor) in lung cancer with
transesophageal ultrasonography].
AB - Transesophageal sonography was originally used to assess esophageal-gastric
neoplasm. The technique may also be useful in the evaluation of pulmonary
neoplasms for possible mediastinal involvement, with regard to both T and N
factors. OBJECTIVE: To consider the validity of this minimally-invasive technique
for assessing possible mediastinal involvement by direct tumoral invasion (T4)
and to help obtain the most accurate staging of lung cancer. PATIENTS AND
METHODS: Sixteen patients with confirmed histopathological diagnoses of pulmonary
neoplasm were examined by transesophageal sonography in order to evaluate
possible mediastinal involvement. They had previously been classified by computed
tomography as T4 (12 patients) or possible T4 (4 patients). Mediastinal
involvement was also assessed by mediastinotomy or thoracotomy in 15 of the 16
patients. RESULTS: Transesophageal sonography revealed mediastinal involvement in
eight of the 16 patients; the rest had no such involvement. Surgical exploration
of the mediastinum confirmed involvement in seven of those who had been so
classified by sonography (with the remaining patient not having been assessed
surgically). Among the eight patients who were considered free of mediastinal
involvement, there was in fact none, although we found previously undetected
infiltration of the posterior surface of the right pulmonary artery in one
patient. Sensitivity was 87.5%, specificity 100% and accuracy 93.3%. CONCLUSION:
Transesophageal ultrasound is a diagnostic tool that can provide additional
information to complement other diagnostic strategies.
PMID- 11004988
TI - [Rehabilitation of respiratory muscles in COPD].
PMID- 11004989
TI - [Beta-agonists in the treatment of bronchial asthma].
PMID- 11004990
TI - [Acute lipoid pneumonia caused by accidental aspiration of vaseline used in
nasogastric intubation].
AB - Exogenous lipoid pneumonia is a rare disease which is often underdiagnosed.
Exogenous lipoid pneumonia has traditionally been considered a chronic process
secondary to continued aspiration or inhalation of fatty substances. In its acute
form exogenous lipoid pneumonia sometimes coincides with accidental massive
aspiration of lipidic material, as has been traditionally described for fire
eaters. We review the literature and report a case of acute lipoid pneumonia
secondary to accidental aspiration of vaseline used to place a nasogastric tube,
which had been inserted for gastric lavage after a suicide attempt by flurazepam
ingestion.
PMID- 11004991
TI - [Hemothorax as complication of transjugular hepatic biopsy].
PMID- 11004992
TI - [Pleural effusion as presentation form of vertebral osteomyelitis of bacterial
origin].
PMID- 11004993
TI - [Diagnosis of idiopathic pulmonary hemosiderosis].
PMID- 11004994
TI - Patient safety and clinical engineering.
PMID- 11004995
TI - Patient safety and clinical engineering.
PMID- 11004996
TI - Skin preparation to reduce ECG artifact.
PMID- 11004997
TI - Successful PACS implementation: the importance of planning and maintenance.
PMID- 11004998
TI - A feasibility study of multispectral image analysis of skin tumors.
AB - To develop a noninvasive, early-detection method for skin cancers, a feasibility
study of multispectral image analysis was investigated. The three most frequently
occurring skin cancer types, ten basal-cell carcinomas (BCCs), ten squamous-cell
carcinomas (SCCs) and five malignant melanomas (MMs) were studied, along with ten
normal moles. Images were acquired by a charge-coupled device camera using eight
narrow-band filters ranging from 450 nm to 800 nm, at 50-nm intervals. To extract
main features of these tumors, principal components analysis (PCA) was performed,
because it projects the multidimensional (here, eight-dimensional) data in the
direction of maximum data variance. Then, the primary PCA components for red,
green, and blue subset images were analyzed in terms of hue-saturation-intensity
(HSI). By hue distributions, the BCCs and SCCs were differentiated from the MMs
and normal moles. Texture information was used to further classify tumor types
after the HSI analysis. The texture analysis, performed using a spatial gray
level co-occurrence matrix (SGCM), could separate MMs from normal moles. The BCCs
and SCCs were further studied by Fisher's linear discriminant analysis.
Distribution was described as a Gaussian mixture model. By this classification
procedure, seven BCCs, eight SCCs, five MMs, and ten NMs were correctly
classified. Three BCCs and two SCCs were unseparable. Thus, multispectral skin
cancer image analysis has potential to diagnose skin cancers.
PMID- 11004999
TI - A novel device for measuring the effect of cholesterol on the release of oxygen
from red blood cells into myocardial tissue.
AB - A novel method has been devised to measure the effect of cholesterol on the
release of oxygen (O2) from the red blood cell (RBC) into a tailored environment,
which can be made to mimic myocardial tissue. Cholesterol affects the cell
membrane of the RBC and thus the release of O2 into tissue. While this is true of
all tissue, the myocardium is especially sensitive because of its critical
nature, its high O2 requirements, and the shortness of time that arterial blood
spends in the muscle. Calculations are presented that show that the release time
for O2 from RBCs is close to the residence time of the RBC in the coronary
system. Sequential measurements of blood oxygen saturation (SO2) are made when
oxygenated blood is subjected to conditions similar to those in the myocardium.
The natural logarithm of the relative value of the SO2 at time t compared with
the initial value of the SO2 can be fitted to a straight line whose slope is
proportional to the parameters of the RBC membrane, the sample size, the
hematocrit, and the diffusion parameters of the apparatus. This value is used to
estimate the effects of cholesterol-lowering treatments on O2 release. This test
will serve as a valuable adjunct to or replacement for stress tests in the
evaluation of coronary artery disease, especially in patients whose physical
conditions make standard stress testing painful or risky.
PMID- 11005000
TI - Implementing the FDA performance standard on electrode lead wires and patient
cables in hospitals.
AB - The U.S. Food and Drug Administration (FDA) Performance Standard on Electrode
Lead Wires and Patient Cables became mandatory for all relevant devices on May 9,
2000. The standard requires that any lead wire or patient cable that has contact,
temporary or permanent, with a patient, should not allow the connection of the
patient to the earth or possibly hazardous voltages. This article advises those
hospitals and other healthcare facilities that have not completed the upgrades of
wires and cables on how to complete this task.
PMID- 11005001
TI - Improving team performance: understanding the differences between teams and work
groups.
PMID- 11005002
TI - Network masks and Internet protocol addressing.
PMID- 11005003
TI - Epidemiology of juvenile violence.
AB - It is difficult to review the epidemiology of juvenile violence because few
studies focus specifically on this topic as opposed to childhood aggression or
delinquency in general. More research is needed specifically on juvenile
violence, which is generally measured using official records or self-reports.
Self-report research shows that a substantial fraction of the male juvenile
population commits violence, and that very few violent acts are followed by
arrests or convictions. Racial differences in violence may be explainable by
reference to racial differences in community contexts. There is a great deal of
versatility in juvenile violence. Juveniles who commit one type of violent
offense also tend to commit other types and nonviolent offenses. Violent
offenders tend to be persistent or frequent offenders, and there is little
difference between violent offenders and nonviolent but equally frequent
offenders. Nevertheless, there is some degree of specialization in violence. More
research is needed to investigate whether risk factors exist for violence that
are not risk factors for serious nonviolent delinquency (e.g., biologic factors).
Violent juveniles tend to have co-occurring problems such as victimization,
substance abuse, and school failure. Often, they might be described as multiple
problem youth. There is considerable continuity from childhood aggression to
juvenile violence. An early age of onset of violence predicts a large number of
violent offenses. The major long-term risk factors for juvenile violence are
individual (high impulsiveness and low intelligence, possibly linked to the
executive functions of the brain), family (poor supervision, harsh discipline,
child physical abuse, a violent parent, large family size, poverty, a broken
family), peer delinquency, gang membership, urban residence, and living in a high
crime neighborhood (characterized by gangs, guns, and drugs in the United
States). More research is needed on interactions among risk factors, and
especially on interactions between biologic and psychosocial risk factors.
Important short-term situational factors include motives of potential offenders
(e.g., anger, a desire to hurt), alcohol consumption, and actions leading to
violent events (e.g., the escalation of a trivial altercation). More specific
research is needed on protective factors against youth violence, for example, by
investigating why aggressive children do not become violent juveniles. More
research is also needed on the development and validation of risk assessment
instruments. To investigate developmental and risk factors for juvenile violence,
longitudinal studies are needed. Such studies should include multiple cohorts, to
draw conclusions about different age groups, and should include both boys and
girls and the major racial and ethnic groups. They should measure a wide range of
risk and especially protective factors. They should be based on large, high-risk
samples, especially in inner-city areas, incorporating screening methods to
maximize the yield of violent offenders while simultaneously making it possible
to draw conclusions about the total population. They should include long-term
follow-up studies to permit conclusions about developmental pathways. They should
make a special effort to study careers of violence and to link developmental and
situational data. It will not be easy to mount new longitudinal studies focusing
specifically on juvenile violence, but such studies are needed to advance
knowledge about the epidemiology of juvenile violence, including risk factors and
developmental pathways.
PMID- 11005004
TI - Sociologic perspectives on juvenile violence.
AB - In sum, there are four sets of social factors that help us understand why
juvenile violence appears when, and where, it does, and why some communities and
entire societies are persistently wracked by youth violence whereas others are
largely spared its worst expressions. When it comes to the first three factors in
particular--deprivation, disorganization, and brutalization--the evidence for
these links is as strong as anything in social science, and that evidence is
supported by a variety of sources and a variety of methods of investigation. Such
investigation includes the knowledge we gain through social intervention. Some of
the most effective violence prevention programs are successful precisely because
they confront and deflect the social forces that otherwise often lead to
violence. Consider, for example, the home-visiting programs that work with poor
parents in disorganized communities to lower the risks of child abuse; and some
of the more "holistic" or "multisystemic" efforts to work with violent juvenile
offenders. The best of these programs work by tackling the problems of social
isolation and lack of supports in the community, as well as immediate issues of
economic survival for vulnerable families and children. More generally, we know
that the availability of steady and rewarding work in the future, of the kind
that can reliably sustain a family, is one of the most important factors allowing
some youths to "desist" from violence as they mature. These conclusions give us
much to be encouraged about, and much to be alarmed about. On the one hand,
understanding that youth violence often is rooted in a set of adverse social
conditions that are identifiable, and potentially modifiable, is a fundamentally
optimistic message. It reminds us that the level of juvenile violence we suffer
in America today is neither fated nor inevitable. Other societies that are in
many respects much like us suffer far less of it; so could we, and we
increasingly understand some of the ways in which we could make that happen. We
know that some programs designed to increase opportunities and supports for high
risk youth and families do work, and we know that there are broader social and
economic policies--policies that are not abstract visions, but have actually been
put into place in societies much like our own--that can significantly diminish
the pressures toward violence that are bred by poverty and social insecurity
among the young. But knowing what to do is one thing, and actually doing it is
another. In this there is much reason for concern. The 7-year economic boom that
began in the early 1990s has had salutary effects on youth violence, mainly by
providing improved economic opportunities for low-income youth and, accordingly,
diminishing the appeal of illegal activities. Despite that extraordinary burst of
sustained prosperity, however, too many of America's youth remain impoverished,
sometimes desperately so: the boom has had only limited effect on our
disturbingly high rates of family poverty, which continue to tower above those of
comparable industrial societies. And if the boom should come to an end, and we
enter again into a period of rising joblessness for youth and young adults, then
much, or all, of the recent gains could be quickly lost. The positive economic
trends that have helped take the edge off serious juvenile violence in the past
few years, in short, are both partial and fragile. Worse, some of our recent
social and economic policies, at both state and federal levels, are working in
the opposite direction. Some variants of welfare reform, for example, have tossed
many vulnerable families off of public assistance without offering solid economic
opportunities in its place. Many more families face this future as federal time
limits on public welfare increasingly come into play. Given what we know about
the links between deprivation and youth violence, this is not a development we
can celebrate. (ABSTRACT TRUNCATED)
PMID- 11005005
TI - Genetics and violence.
AB - As is evident from this brief review, the genetic study of violence is maturing
at an ever-increasing rate; much more work is needed to examine specific
molecular genetic markers and their associated phenotypes, particularly in
subjects with juvenile onset. It is also becoming clear that more work is needed
to help delineate the specific phenotypes that are being transmitted within
families. It is unlikely that we will find a gene or genes that are both
necessary and sufficient for the manifestation of aggression and violence. It is
more likely that specific genes will be associated with discrete factors that
either increase the risk for the expression of violence or that are components of
the violent phenotype. Thus, in addition to continuing research that examines the
role of specific genetic factors in the manifestation of violence, more work is
needed that will help further develop the nosology of violence and related
behaviors. As noted previously, an understanding of the inherited phenotype is
critical in the study of any disorder. It is especially important in the study of
complex behaviors such as violence in which there may be several behavioral
components that comprise the complete diagnostic category.
PMID- 11005006
TI - Neurologic evaluation of violent juveniles.
AB - Any juvenile who has acted violently requires a systematic, meticulous neurologic
evaluation. There is no substitute for an adequate medical, family, and social
history, the latter focusing on abuse and neglect. Evaluation should include a
full physical and a conventional neurologic examination. Additionally, the
physical, neurologic examination must include tests of cerebral-cortical
function. The history and physical examination usually will indicate the
diagnosis. A neuropsychologic evaluation of higher cerebral functions, including
tests of frontal functions, should also be done in most cases. Some specific
causes of brain disease can be identified by appropriate blood and urine tests,
waking and sleep EEGs, and neuroimaging investigations. In general, positive
findings are more significant than negative findings. If the physical examination
and psychological tests are negative and the MR imaging shows a brain tumor, the
patient has a brain tumor. If the neurologic or neuropsychological examinations
demonstrate brain dysfunction, the patient has brain dysfunction, even if MR
imaging is normal.
PMID- 11005007
TI - Mental illness, neuropsychologic deficits, child abuse, and violence.
AB - This review of the psychiatric, neuropsychological, and familial contributions to
aggressive behavior makes clear that conduct disorder is not a single diagnostic
entity. It is, rather, the final common pathway of the interaction among a
variety of different kinds of intrinsic vulnerabilities and environmental
stressors. In every aggressive child all of these vulnerabilities (none of which
necessarily meets full criteria for a specific DSM-IV diagnosis) and stressors
must be considered and, if present, addressed systematically. We know that
psychotic symptomatology, especially paranoia, combined with neuropsychological
vulnerabilities and a history of severe abuse become a recipe for violence, and
the more impaired the child, if abused, the more violent the child will become as
an adolescent and adult. The clinician must, therefore, think of himself or
herself as the only knowledgeable adult who will ever take the time to discover
these ingredients and deal with the violent child positively and therapeutically.
PMID- 11005008
TI - Diagnostic evaluation of the violent child and adolescent.
AB - The diagnostic evaluation of the violent child and adolescent is a collaborative
exercise, requiring diverse expertise. Ironically, after systematic,
comprehensive psychiatric, neurologic, psychologic, neuropsychologic,
psychoeducational, family, and social evaluations have been completed, the
clinician probably will not be able to make a hard and fast DSM-IV diagnosis;
that is, unless the clinician is satisfied with fitting the behavioral pieces
into the Conduct Disorder category and ignoring the rest of the clinical data.
From time to time the clinician will be able to diagnose a bipolar mood disorder
underlying a violent youngster's behavior. Occasionally the clinician will
recognize paranoid schizophrenia motivating a particularly heinous or bizarre
violent act. Most often the clinician will be faced with a variety of different
kinds of psychiatric, neurologic, cognitive, and environmental vulnerabilities
that have come together and created a violent child or adolescent. That's fine
because almost invariably each discovered vulnerability has implications for
treatment. The clinician evaluating a violent child or adolescent must overcome
his or her initial disgust or anger at the youngster's behaviors and resist the
impulse to dismiss the child as conduct disordered, as an incipient psychopath.
That diagnosis leads nowhere. The identification of vulnerabilities leads to
specific interventions and ultimately to the prevention of future violence.
PMID- 11005009
TI - Treatments for aggressive and antisocial children.
AB - Many different types of treatment have been applied to conduct-disordered youths.
Unfortunately, little outcome evidence exists for most of the techniques. Three
treatments with the strongest evidence to date were highlighted in this article:
PMT, PSST, and MST. Parent management training is directed at altering parent
child interactions in the home, particularly those interactions related to child
rearing practices and coercive interchanges. Cognitive problem-solving skills
training focuses on cognitive processes that underlie social behavior.
Multisystemic therapy focuses on the individual, family, and extrafamilial
systems and their interrelations as a way to reduce symptoms and to promote
prosocial behavior. Each of these treatments has multiple controlled studies on
its behalf, and some of the techniques (e.g., PMT) have been extraordinarily well
evaluated. Significant issues remain to be addressed to accelerate treatment
advances. We cannot yet say that one intervention can ameliorate conduct disorder
and overcome the poor long-term prognosis. On the other hand, much can be said.
Much of what is practiced in clinical settings is based on psychodynamically
oriented treatment, general relationship counseling, generic family therapy, and
group therapy (with antisocial youths as members). These and other procedures,
alone and in various combinations in which they are often used, have not been
evaluated carefully in controlled trials. Of course, absence of evidence is not
tantamount to ineffectiveness. At the same time, promising treatments have
advanced considerably, and a very special argument might be needed to administer
treatments that have neither basic research on their conceptual underpinnings in
relation to conduct disorder nor outcome evidence from controlled clinical trials
on their behalf. Promising treatments, at best, leave important questions
unanswered. Further development of treatments clearly is needed. Apart from
treatment studies, further progress in understanding the nature of conduct
disorder is likely to have very important implications for improving treatment
outcome. Improved triage of patients to treatments that are likely to work will
require understanding of characteristics of children, parents, and families that
will make them more or less amenable to current treatments.
PMID- 11005011
TI - Ethical implications of what we know about violence.
AB - This article explores the moral implications of the previous articles in this
volume. It looks at our knowledge regarding the neuropsychiatric and
environmental influences on violence in light of concepts of justice, virtue, and
responsibility.
PMID- 11005012
TI - The centrosome and parthenogenesis.
PMID- 11005010
TI - Forensic aspects of juvenile violence.
AB - The juvenile justice system was created because it was recognized that youthful
offenders needed to be managed differently from adults. They were to receive
habilitation services instead of punishment. It is now more than a century since
the creation of the first juvenile court. After 67 years, the US Supreme Court,
in Kent v United States stated that the model was not working because juveniles
in the criminal justice system received no treatment and they had no rights.
Because the issue that had been appealed was the lack of rights (not lack of
treatment), the Court mandated that juveniles, like adults, be given certain
rights. The following year, in In re Gault, the Court expanded these rights.
Subsequent Supreme Court cases have dealt with these kinds of issues--that is,
whether juvenile offenders are entitled to the same rights as adults and subject
to the same penalties. The Supreme Court has never heard a "right to treatment"
case, which is the other part of the juvenile court system. Cases have been
brought in lower courts (e.g., Nelson v. Heyne, 1972) alleging inadequate
treatment services, but no national impact has resulted. Thus, in general,
children in the juvenile court system do not have an enforceable right to
treatment and can obtain only what services are available in their jurisdictions.
The services often are woefully inadequate. Sentencing a youth to probation, with
the requirement that he or she participate in counseling or mental health
treatment, is meaningless if services are not available. Community-based, model
programs that provide effective treatment do exist. They are, as yet, the rare
exception rather than the norm and, therefore, are not available to most youthful
offenders. Incarcerated juveniles, obviously, cannot avail themselves of
community programs. Litigation to give these youth the same rights as adults in
penal institutions is not the answer because incarcerated adults don't have a
right to treatment, only a right to be free from "deliberate indifference" to
their medical needs. It is hoped that a way will be found to provide effective
services for the juvenile delinquent population. Federal laws have been enacted
to mandate special services for educationally handicapped children. Those
statutes, and litigation based on them, have led to some improvements for that
group of children. Perhaps the same can be accomplished for the youthful offender
population. Mandatory early intervention will serve them far better than
mandatory waiver to adult court or incarceration in adult prison.
PMID- 11005013
TI - gamma-Tubulin.
PMID- 11005014
TI - gamma-Tubulin complexes and their role in microtubule nucleation.
PMID- 11005015
TI - gamma-Tubulin of budding yeast.
PMID- 11005016
TI - The spindle pole body of Saccharomyces cerevisiae: architecture and assembly of
the core components.
PMID- 11005017
TI - The microtubule organizing centers of Schizosaccharomyces pombe.
PMID- 11005018
TI - Comparative structural, molecular, and functional aspects of the Dictyostelium
discoideum centrosome.
PMID- 11005019
TI - Are there nucleic acids in the centrosome?
PMID- 11005021
TI - Centriole duplication and maturation in animal cells.
PMID- 11005020
TI - Basal bodies and centrioles: their function and structure.
PMID- 11005022
TI - Centrosome replication in somatic cells: the significance of G1 phase.
AB - Proper cell division requires that the cell be able to form a bipolar spindle
during mitosis. To achieve this, the centrosome must be replicated accurately
during interphase. Our understanding of the mechanisms that allow centrosome
doubling to be coordinated with other cell cycle progression processes is
advancing at a rapid pace. Several different experimental systems have been
developed that are allowing detailed studies of centrosome replication. For
example, the identification of mutants in yeast that are unable to duplicate the
SPB accurately during interphase has provided important insights concerning
centrosome duplication. In addition, intact embryonic cells and extracts prepared
from unfertilized eggs are powerful tools for investigating the molecular
regulation of centrosome doubling during the cell cycle. Many of the observations
from these embryonic systems are directly applicable to understanding centrosome
doubling in somatic cells. Finally, transgenic mouse models and cultured
mammalian cell systems have been developed for analyzing the regulation of
centrosome doubling in cells with more complex cell cycles. As our knowledge of
the cell cycle advances, particularly our understanding of the intricate series
of events that must occur for somatic cells to traverse G1 phase, it should be
possible to use the systems that have been developed to determine how the
replication of the centrosome is coordinated with other cell cycle progression
processes. The next few years should see rapid advances in our understanding of
this critical cell biological process.
PMID- 11005023
TI - The coordination of centrosome reproduction with nuclear events during the cell
cycle.
PMID- 11005024
TI - Regulating centrosomes by protein phosphorylation.
PMID- 11005025
TI - The role of the centrosome in the development of malignant tumors.
PMID- 11005026
TI - The centrosome-associated Aurora/Ipl-like kinase family.
AB - Because of the well-known role of the centrosome and mitotic apparatus in genome
partitioning in normal cells, defects in pathways essential for mitotic
regulation are likely implicated in the cascade of events leading to aneuploidy
and neoplasia. Exogenous overexpression of AIM-1, for example, produces
multinuclearity in human cells and increased ploidy as well as aneuploidy
(Tatsuka et al., 1998). Overexpression in colorectal tumor cell lines is thought
to have a causal relationship with multinuclearity and increased ploidy.
Cytokinesis error caused by AIM-1 overexpression is a major factor in the
predisposition to cancer. As previously mentioned, the involvement of
BTAK/aur2/AIK in centrosome amplification and its oncogenic activity are
compelling. Aur2 has also been implicated in oncogenesis, and defects in
kinetochore function leading to chromosome instability in human tumors should not
be minimized (Farruggio et al., 1999). Further studies are needed to provide a
clearer definition of how these kinetic proteins are linked and regulated in
normal mitosis and cancer. Thus, Boveri appears to have been correct in
formulating his early hypothesis that a defective mitotic apparatus and
centrosome number were central and causative in chromosome missegregation and
cancer. One hundred years later, at the onset of a new millennium and with light
years of advanced technology in our favor, we are just now beginning to piece
together the enzymes, substrates, and signaling pathways that support and explain
his long-ignored but prophetic claim.
PMID- 11005027
TI - Centrosome reduction during mammalian spermiogenesis.
PMID- 11005028
TI - The centrosome of the early C. elegans embryo: inheritance, assembly,
replication, and developmental roles.
PMID- 11005029
TI - The centrosome in Drosophila oocyte development.
AB - The Drosophila oocyte is a highly specialized cell type whose development
utilizes MTOCs in various contexts. Figure 4 (see color insert) summarizes the
characteristics of the MTOCs at different stages of oogenesis. Polarized mitoses
are required to achieve oocyte determination. In the asymmetric germ-cell
divisions that culminate in the egg chamber, the mitotic centrosomes are anchored
to the spectrosome or fusome in order to produce the regular branching pattern of
the cyst cells. It appears that the primary role of the fusome is to orchestrate
the polarity and synchrony of oogenic mitoses. In the absence of fusomes or
anchored spindles, the regular interconnected cyst network is lost and the oocyte
does not differentiate. It is not known if the spindle itself is asymmetric, or
whether either centrosome has equal potential to interact with the fusome.
Several models can explain the need for polarized mitoses for oocyte
differentiation. In one, an unequal distribution of unknown oocyte
differentiation factors occurs from as early as the first cystoblast division.
Here, the fusome may be required for the distribution of the factors. In another
model, there is a mechanism that measures the number of ring canals in the cell,
limiting the choice of oocyte to two potential pro-oocytes. In this model,
polarized, synchronous divisions must occur to produce only two cells with the
highest number of ring canals. In both of these models the centrosome plays an
indirect role. A critical event in the determination of the oocyte is the
formation of the MTOC. The oocyte MTOC forms shortly after completion of the germ
cell mitoses and establishes a microtubule array along which factors required for
oocyte determination are transported. It is unclear how this single MTOC forms in
the 16-cell cyst, how the centrosomes become inactivated in the adjoining 15
nurse cells, or why the inactivated centrioles are transported into the oocyte.
No molecular components of the MTOC are known except for centrosomin, which
accumulates at the MTOC relatively late, at approximately stage 5 or 6 of
oogenesis. The MTOC plays a central role in establishing the oocyte's polar
coordinates. The oocyte microtubule array is required for the polar localization
of axis-determining factors. At midoogenesis the MTOC appears to mediate the
reversal of the microtubule array and the migration of the nucleus in the oocyte.
The posterior follicle cells signal this reversal after receiving the gurken
signal. What changes occur at the MTOC to trigger this cytoskeletal
rearrangement? A better understanding of the MTOC's molecular components is
necessary before we can begin to unravel the mechanisms underlying these events.
The morphology of the MTOC changes after it shifts to the oocyte anterior.
Staining with anti-centrosomin antibodies shows that the MTOC changes from
discrete nucleus-associated bodies into a broad structure associated with the
anterior cortex. The molecular mechanisms underlying this structural
rearrangement of the MTOC at midoogenesis are presently unknown. Meiosis I occurs
in the absence of centrosomes, but meiosis II spindles are linked by a shared,
acentriolar, astral MTOC. The organization of the meiosis I spindle poles
requires the NCD motor protein; however, the meiosis I spindle poles are
acentriolar and contain no known centrosomal core proteins. The meiosis II astral
spindle pole has a unique ring-shaped morphology and contains centrosomal
proteins, such as gamma-tubulin. Strong mutations in the maternal gamma Tub37C
gene do not block meiosis I, but prevent the progression of meiosis II.
PMID- 11005030
TI - The centrosome in early Drosophila embryogenesis.
PMID- 11005031
TI - Centrosome maturation.
AB - In the past, centrosome maturation has been described as the change in
microtubule nucleation potential that occurs as cells pass through specific
phases of the cell cycle. It is suggested that the idea of centrosome maturation
be expanded to include gain of functions that are not necessarily related to
microtubule nucleation. Some of these functions could be transient and dependent
on the temporary association of molecules with the centrosome as cells progress
through the cell cycle. Thus, the centrosome may best be viewed as a site for
mediating macromolecular interactions, perhaps as a central processing station
within the cell. The centromatrix, a relatively stable lattice of polymers within
the centrosome's PCM, could serve as a scaffold for the transient binding of
mediator molecules, as well as allow the dynamic exchange of centrosome
constituents with a soluble cytoplasmic pool. New evidence adds support to the
idea that centrioles are crucial for the maintenance of PCM structure. However,
significant evidence indicates that aspects of centrosome structure and function
can be maintained in the absence of centrioles. In the case of paternal
centrosome maturation, sperm centrioles may not contain an associated
centromatrix. It is proposed that regulation of paternal centrioles or centriole
associated proteins could mediate centriole-dependent centromatrix assembly
following fertilization. Thus, regulation of centromatrix-centriole interactions
could be involved in maintaining the integrity of the centrosome's PCM and play
an important role in centrosome disassembly during cell differentiation and
morphogenesis.
PMID- 11005032
TI - Syndromes of disseminated intravascular coagulation in obstetrics, pregnancy, and
gynecology. Objective criteria for diagnosis and management.
AB - This article presents current understanding of the causes, pathophysiology,
clinical, and laboratory diagnosis, and management of fulminant and low-grade
DIC, as they apply to obstetric, pregnant, and gynecologic patients. General
medical complications leading to DIC, which may often be seen in these patients,
are also discussed. Considerable attention has been given to interrelationships
within the hemostasis system. Only by clearly understanding these
pathophysiologic interrelationships can the obstetrician/gynecologist appreciate
the divergent and wide spectrum of often confusing clinical and laboratory
findings in patients with DIC. Objective clinical and laboratory criteria for
diagnosis of DIC have been outlined to eliminate unnecessary confusion and the
need to make empiric decisions regarding the diagnosis. Particularly in the
obstetric patient, if a condition is observed that is associated with DIC, or if
any suspicion of DIC arises from either clinical or laboratory findings, it is
imperative to monitor the patient carefully with clinical and laboratory tools to
assess any progression to a catastrophic event. In most instances of DIC in
obstetric patients, the disease can be ameliorated easily at early stages. Many
therapeutic decisions are straightforward, particularly in obstetric and
gynecologic patients. For more serious and complicated cases of DIC in these
patients, however, efficacy and choices of therapy will remain unclear until more
information is published regarding response rates and survival patterns. Also,
therapy must be highly individualized according to the nature of DIC, patient's
age, origin of DIC, site and severity of hemorrhage or thrombosis, and
hemodynamic and other clinical parameters. Finally, many syndromes that are often
categorized as organ-specific disorders and are sometimes identified as
independent disease entities, such as AFE syndrome, HELLP syndrome, adult shock
lung syndrome, eclampsia, and many others, either share common pathophysiology
with DIC or are simply a form of DIC. These entities represent the varied modes
of clinical expression of DIC and illustrate the diverse clinical and anatomic
manifestations of this syndrome.
PMID- 11005033
TI - Oral contraceptive pills and hormonal replacement therapy and thromboembolic
disease.
AB - The risk of thromboembolic complications with the use of second and third
generation oral contraceptives is minimal and probably related to underlying
congenital or acquired thrombophilic states. Estrogen dose-dependency leads to
increased thrombin generation and increased plasmin generation. There is no
convincing evidence that the balance between clotting and fibrinolysis is
disturbed. The risk of venous thromboembolism with pregnancy is greater than with
oral contraceptives. Hormone replacement therapy is safe for healthy women, and
the benefits far outweigh the potential risks.
PMID- 11005034
TI - Iron deficiency in pregnancy, obstetrics, and gynecology.
AB - Iron deficiency remains a major health risk in the United States, despite the
apparent availability of a high-quality diet. In the United States, at least 7.8
million adolescent girls and premenopausal women are iron-deficient. Worldwide,
the challenge of identifying and treating iron deficiency is enormous. Physicians
involved in the primary care and in the obstetric and gynecologic care of women
of all ages must be aware of the nature of the problem and the correct approach
to screening, diagnosis, and treatment. The potential benefit to newborns and
infants and to their mothers is substantial. Furthermore, a thorough diagnostic
evaluation has considerable potential for uncovering a potentially lethal
disease, such as gastrointestinal malignancy, in a curable phase.
PMID- 11005035
TI - Clinical and laboratory features and sequelae of deficiency of folic acid
(folate) and vitamin B12 (cobalamin) in pregnancy and gynecology.
AB - Classically, deficiency of folic acid (folate) or vitamin B12 (cobalamin) was
recognized by the presence of a macrocytic anemia resulting from megaloblastic
changes in the bone marrow. A markedly changing paradigm has identified both new
mechanisms for altered folate and cobalamin status and new sequelae and clinical
interrelationships that include altered mechanisms of absorption, a changing
pattern of neurologic deficits, an increased risk of vascular occlusive lesions,
and an important relationship with the mechanisms of neoplastic transformation.
Several of these newer characterizations relate to issues of neoplasia in the
nonpregnant woman and to issues in pregnancy, such as the potential for
developmental abnormalities of the fetal nervous system.
PMID- 11005036
TI - Gestational thrombocytopenia and immune thrombocytopenias in pregnancy.
AB - Appropriate management of thrombocytopenia in the pregnant patient is important
for the well-being of both mother and fetus. The healthy-appearing mother with
mild thrombocytopenia may have either gestational benign thrombocytopenia, which
does not produce fetal thrombocytopenia, or immune-mediated thrombocytopenia,
which can produce fetal thrombocytopenia. These two types of pregnancy-associated
thrombocytopenias can be differentiated. Gestational benign thrombocytopenia is
initially discovered during pregnancy, and in these patients a reliable test for
antiplatelet antibody is usually negative. Conversely, patients with immune
mediated thrombocytopenia may have a history of thrombocytopenia before the
pregnancy, and these patients usually have a detectable antiplatelet antibody.
The pregnancy patient who presents with a normal platelet count and a history of
neonatal alloimmune thrombocytopenia in a prior pregnancy or with a history of an
infant of a close relative with NAT must be carefully monitored. Antiplatelet
antibody assays performed on mother's and baby's blood will help determine if an
antiplatelet antibody is present in maternal plasma, if the antibody reacts with
the baby's platelets, and (with appropriate typing plasma) the antigenic
specificity of the maternal and fetal platelets. In addition, antigenic typing of
the father's platelets will help determine the risk of NAT in the current
pregnancy. If a fetus is at risk for severe immune-mediated thrombocytopenia from
either an autoantibody or an alloantibody, the fetal platelet count should be
measured, if possible, from blood obtained by umbilical cord puncture. If the
fetal platelet count is less than 50,000/microL or cannot be measured but is
thought to have a high probability of being less than 50,000/microL, strong
consideration should be given to a cesarean delivery.
PMID- 11005037
TI - Recurrent miscarriage syndrome and infertility caused by blood coagulation
protein or platelet defects.
AB - Recurrent miscarriage syndrome and infertility are common problems in the United
States. Recurrent miscarriage affects more than 500,000 women annually. If
properly screened through a cost-effective protocol, the cause will be found in
almost all women. The most common singular defect in women with RMS is a
hemostasis defect, and if a thorough APLS evaluation is performed, the most
common of these is found to be APLS. Other hereditary and acquired procoagulant
defects are also commonly found, if looked for. It is important to evaluate women
with RMS appropriately, because if a cause for the RMS is found, most women will
achieve normal-term delivery. Hemorrhagic defects are rare hemostasis causes of
RMS, but these defects also are treatable in many instances and should be
considered in appropriate women. Treatment of the common procoagulant defects
consists of preconception low-dose ASA at 81 mg/day followed by immediate
postconception low-dose unfractionated porcine heparin. LMWH may be a suitable
alternative.
PMID- 11005038
TI - Antithrombotic therapy in high-risk pregnancy.
AB - Venous thromboembolism remains a major cause of morbidity and mortality
associated with pregnancy and puerperium. Specific risk factors for this disorder
can be identified before or during pregnancy and delivery. The heritable defects
believed to be associated with venous thrombosis are factor V Leiden mutation;
elevated antiphospholipid antibodies; and deficiencies of antithrombin, protein
C, and protein S. Women with a history of thromboembolism and thrombophilia
should receive antenatal and postpartum thrombosis prophylaxis.
PMID- 11005039
TI - Antithrombotic therapy in gynecologic surgery and gynecologic oncology.
AB - The European Consensus Conference has assessed the risk for thrombotic
complications for most women undergoing gynecologic surgery and found it to be
moderate. Nonetheless, it is important to analyze a patient's individual risk
before surgery so that appropriate thrombosis prophylaxis can be given if
increased risk is determined. Malignancy accounts for most thrombotic
complications among gynecologic patients. Patients with known malignancies should
receive prophylaxis during surgery, and some patients with breast cancer should
receive prophylaxis during chemotherapy. Heparin, and low-molecular-weight
heparin in particular, may favorably influence the outcome of cancer in some
patients and treatment with these agents is currently under investigation in a
number of trials as a new approach to anticancer therapy.
PMID- 11005040
TI - Hemorrhagic problems in obstetrics, exclusive of disseminated intravascular
coagulation.
AB - During pregnancy many physiologic changes occur that result in an increase in
coagulation factors and a decrease in fibrinolytic activity. Because hemorrhage
during pregnancy is a major cause of maternal morbidity, it is important to
recognize and understand the pathophysiology of hereditary and acquired bleeding
disorders. This article reviews von Willebrand's disease types 1, 2, and 3 and
acquired hemophilia.
PMID- 11005041
TI - Human platelet thrombin receptors. Roles in platelet activation.
AB - Platelets are essential participants in hemostasis and thrombosis. Platelets
normally circulate in blood as discoid resting cells that become critical
constituents of hemostatic plugs or arterial thrombi only after specific
receptors on platelet membranes interact with their ligands (agonists) to
initiate the reactions that lead to platelet activation. The well-characterized
events associated with platelet activation include activation of membrane
receptors, shape change, granular secretion, cytoskeletal reassembly, platelet
cohesion, and aggregation. The plasma protease alpha-thrombin is the most potent
physiologic platelet agonist; this enzyme has other key roles in hemostasis, in
the genesis of arterial thrombi, and in embryonic development, inflammation,
wound healing, and cell proliferation.
PMID- 11005042
TI - High-dose right unilateral ECT.
PMID- 11005043
TI - Quantitative EEG during seizures induced by electroconvulsive therapy: relations
to treatment modality and clinical features. I. Global analyses.
AB - This study examined the effects of electroconvulsive therapy (ECT) treatment
conditions, patient individual difference factors, and clinical outcome on global
electroencephalogram (EEG) power during and immediately following ECT-induced
seizures. Sixty-two patients were randomized to ECT conditions differing in
electrode placement (right unilateral versus bilateral) and stimulus dosage (just
above seizure threshold versus 2.5 times seizure threshold). At the second and
penultimate treatments, global total power (1.5-28.5 Hz) and global power in
specific frequency bands were quantified in 19-lead EEG recordings of the
generalized seizure and the immediate postictal period. Seizures induced with
high dosage, and to lesser extent, with bilateral electrode placement, resulted
in greater global power. Patient age, initial seizure threshold, and baseline
depression severity were inversely related to global power during seizures. While
superior clinical outcome following ECT was associated with greater global power
during seizures, this effect was small. The factors associated with more robust
seizure expression also resulted in greater postictal bioelectric suppression.
Associations with treatment parameters and patient variables were stronger at the
second than penultimate treatment. We conclude that manipulations of ECT
technique strongly determine the magnitude of seizure expression, but relations
with clinical outcome are weak. The findings raise doubt about the clinical
utility of algorithms based on analysis of EEG features to guide ECT parameter
selection.
PMID- 11005044
TI - Quantitative EEG during seizures induced by electroconvulsive therapy: relations
to treatment modality and clinical features. II. Topographic analyses.
AB - This study tested three alternative theories of the mechanisms of therapeutic
action of electroconvulsive therapy (ECT). The theories differed in predictions
about the global and topographic effects of effective and ineffective forms of
ECT on electroencephalogram (EEG) seizure expression. At the second treatment, 19
lead EEG recordings were obtained in 57 depressed patients randomized to
conditions that differed in ECT electrode placement and stimulus dosage. Power in
the delta frequency band was quantified during the seizure and analyzed with
traditional multivariate methods and the Scaled Subprofile Model. Electrical
dosage of the ECT stimulus had a powerful effect on ictal global delta power and,
more so, than electrode placement. Greater ictal global delta power was
associated with superior therapeutic outcome, but the magnitude of this effect
was small. Effective forms of ECT resulted in a topography where delta power was
accentuated in prefrontal EEG sites. High dosage right unilateral ECT also
resulted in stronger asymmetry in prefrontal regions than the ineffective, low
dosage right unilateral ECT. Greater bilateral generalization of seizure
expression does not appear to be a prerequisite for therapeutic effects. Instead,
more intense seizure expression in prefrontal regions may be critical for
efficacy.
PMID- 11005045
TI - The effect of repeated bilateral electroconvulsive therapy on seizure threshold.
AB - Seizure threshold was measured by empirical titration in 28 patients referred for
bilateral electroconvulsive therapy to treat depressive illness at the outset of
treatment and after another six treatments. No patient was given antiepileptic
drug treatment, and anesthetic technique and concomitant psychotropic drug
treatment were fixed. The average (+/- SD) initial seizure threshold measured by
set charge was 79.5 mC (+/- 33.4 mC), and this increased to 95.5 mC (+/- 37.9
mC). The average percentage increase was 22.8% (95% confidence interval, 13.7% to
31.8%). The seizure threshold measured by set charge did not change in 15
patients (54%), and there was no significant relation between change in seizure
threshold and patient sex, change in seizure duration measured by cuff technique,
or global clinical improvement during the course of treatment.
PMID- 11005046
TI - Electroconvulsive therapy and falls in the elderly.
AB - Electroconvulsive therapy (ECT) is commonly used in the practice of geriatric
psychiatry. Although it has been found to be both safe and effective, one of the
most common complications associated with ECT is falls. A logistic regression
model was created to identify independent risk factors for falls in the elderly.
Two risk factors were identified: the number of ECT treatments and the diagnosis
of Parkinson disease. Further studies are needed to develop strategies aimed at
reducing the number of falls. In the meantime, clinicians need to be aware that
falls represent an important complication associated with ECT.
PMID- 11005047
TI - Seizure threshold estimation by formula method: a prospective study in unilateral
ECT.
AB - Formula methods of estimating seizure threshold in bilateral electroconvulsive
therapy (ECT) have been successful in 75% (at the first ECT) and 80% (at the
sixth ECT) of treatments (Gangadhar et al., 1998). This study showed the same
results for unilateral (UL) ECT patients. Its aim was to compare formula and
titration methods for threshold determination. The seizure threshold (dependent
variable) was determined by the titration method used at the first ECT in
consecutive consenting patients (n = 80) prescribed UL ECT under general
anesthesia. The independent variables were age, gender, diagnosis, illness
severity, concurrent drugs, head circumference, and inion-nasion distance.
Forward, step-wise, linear regression analysis showed age as the only significant
predictor of seizure threshold (15% of variance). A formula based on regression
analysis was prospectively applied in an independent sample (n = 30) of patients
receiving UL ECT using the titration method for threshold determination. The
results calculated a higher threshold than the actual threshold used in 14
patients, a threshold level in 8 patients, and below threshold in 8 patients.
Formula-based estimates would have been successful in 22 (73%) patients, but the
majority of them would have received higher than the recommended stimulus dose.
Titration is the method preferred for clinical use. However, if a patient's
doctor wishes to use the formula-based method, he or she should do so with
specific considerations.
PMID- 11005048
TI - Post-ECT agitation and plasma lactate concentrations.
AB - This prospective study evaluated the hypothesis that emergence agitation after
electroconvulsive therapy (ECT) could be caused by lactate-induced panic
secondary to insufficient neuromuscular blockade. Plasma lactate levels were
measured before and after 245 consecutive ECT sessions in 37 patients monitored
for evidence of post-ECT agitation. ECT was administered using a brief-pulse,
rectangular, constant-current device through bilaterally placed electrodes under
general anesthesia and neuromuscular blockade. Agitation was observed in 7% of
all ECT sessions. No significant difference could be found in pre-ECT lactate
levels. However, mean post-ECT lactate levels in agitated sessions were
significantly greater than those in nonagitated sessions (4.77 versus 2.54
mmol/l, p < 0.05). An increase (+27%) in the pre-ECT succinylcholine dose for
those patients who previously had repeated post-ECT agitation resulted in
cessation of post-ECT agitation and return of the formerly high post-ECT lactate
levels to normal (1.61 versus 2.07 mmol/l). Although the number of patients who
had post-ECT agitation was small, the data support the hypothesis that post-ECT
agitation might be a manifestation of lactate-induced panic.
PMID- 11005049
TI - Electroconvulsive therapy and the alpha-2 noradrenergic receptor: implications of
treatment schedule effects.
AB - Six factorially designed studies evaluated the effects of different schedules of
electroconvulsive shocks (ECSs) on alpha-2 adrenoceptor function in the rat
brain. Attenuation of the hypomotility response to a clonidine challenge was
taken to indicate alpha-2 adrenoceptor downregulation, a putative mediator of
antidepressant action. Six daily and six alternate-day ECSs were shown separately
to produce this receptor change. Three alternate-day ECSs produced comparable
downregulation for a comparable period as six daily ECSs; this suggests that ECS
produces time-dependent effects. No changes were elicited with a single ECS,
which indicates that a single ECS may not influence alpha-2 receptor function.
Three daily ECSs produced brief downregulation, which has implications for
receptor dynamics as a function of the ECS schedule. Finally, maintenance ECSs
sustained alpha-2 adrenoceptor downregulation over 6 weeks, which suggests a
possible neurochemical basis for maintenance electroconvulsive therapy. The
clinical relevance and scope for further research are discussed.
PMID- 11005050
TI - A statewide survey of ECT policies and procedures.
AB - The 1990 American Psychiatric Association (APA) Electroconvulsive Therapy (ECT)
Task Force Recommendations include facility policy and procedure guidelines. The
objectives of this study were to determine and to improve the adherence to the
1990 APA ECT Task Force Recommendations on policies and procedures among the
providers of ECT in Louisiana. Completed surveys on ECT policy and procedures
were obtained from the seven major Louisiana ECT providers from the last quarter
of 1996. Project coordinators distributed copies of the survey results and a
comprehensive set of ECT policies and procedures at a statewide meeting of
participating hospitals during the spring of 1997. Most facilities had policies
for electrical safety of ECT equipment, testing of new ECT equipment, pre-ECT
work-up, ECT informed consent, patient instruction sheets, outpatient ECT,
documentation of ECT procedures, clinical privileging, and ECT quality assurance
monitoring. Subsequent telephone follow-up found that all participants changed
their policies and procedures as a result of the project. Louisiana ECT providers
showed general compliance with the facility policy and procedure aspects of the
1990 APA ECT Task Force Recommendations. The awareness model of guideline
compliance was applicable to improving facility policies and procedures.
PMID- 11005051
TI - ECT in a patient with a deep brain-stimulating electrode in place.
AB - A 68-year-old woman had a deep brain-stimulating electrode placed for worsening
of a long-standing essential tremor. There is currently no data available on the
use of electroconvulsive therapy (ECT) in the presence of the deep brain
stimulator (DBS). We report here the successful use of ECT in this patient with
no adverse effects to the patient or to the DBS. No special provisions were made
with the ECT administration except to ensure that the stimulator was turned off
prior to administration of the ECT series, and remained off through the eight
treatments administered to this patient. Following the course of treatment, her
mood was markedly improved, and she displayed only minor postictal confusion.
PMID- 11005052
TI - ECT in a patient with psychotic retarded depression, metastatic hepatic cancer,
and esophageal varices.
AB - We report a patient with liver disease and esophageal varices who responded to
intensive psychiatric intervention on a medical unit. Her case illustrates the
successful use of electroconvulsive therapy in the presence of varices, and
highlights some precautions that could be taken in treating similar patients.
PMID- 11005053
TI - ECT administration in a patient after craniotomy and gamma knife surgery: a case
report and review.
AB - The safe administration of electroconvulsive therapy (ECT) in a man with steroid
induced depression and a history of craniotomy and gamma knife surgery for two
separate foci of metastatic laryngeal cancer is reported. This is the first
reported case of ECT given to a patient with a history of gamma knife surgery.
The literature on ECT administration to patients with brain masses or a history
of craniotomy is reviewed. The current case report indicates that with careful
medical evaluation, including consultation with neurosurgeons and internal
medicine physicians, ECT may be safely administered to this patient population.
PMID- 11005054
TI - Lithium and maintenance ECT.
AB - A 78-year-old man with a long history of major depression responded well to a
course of ECT but relapsed before maintenance treatments could be started.
Addition of lithium carbonate resulted in a sustained remission with maintenance
treatments. The combination of maintenance ECT and lithium may be safe and
effective in selected cases of refractory depression.
PMID- 11005055
TI - Severe self-injurious behavior associated with treatment-resistant schizophrenia:
treatment with maintenance electroconvulsive therapy.
AB - A 35-year-old man with schizophrenia associated with a 10-year history of
repetitive and often severe self-injurious behaviors was treated successfully
with maintenance electroconvulsive therapy. Initially his condition did not
respond to multiple psychotropic agents (including a year-long trial of
clozapine), 27 hospitalizations, two courses of bilateral electroconvulsive
therapy, and supportive psychotherapy with partial hospitalization. After the
initiation of maintenance electroconvulsive therapy, this patient was able to
tolerate residential placement and begin a work therapy program with only one
instance of self-injurious behavior in the past 17 months.
PMID- 11005056
TI - Ventricular ectopy associated with low-dose intravenous haloperidol and
electroconvulsive therapy.
PMID- 11005057
TI - The rate of ECT use in young people.
PMID- 11005058
TI - Certification in ECT: a rush to judgment.
PMID- 11005059
TI - Transient dissociative identity disorder after electroconvulsive therapy.
PMID- 11005060
TI - Effectiveness of ECT against delirium during an episode of bipolar disorder: a
case report.
PMID- 11005061
TI - The map of dying.
PMID- 11005062
TI - Infectious diseases and medical microbiology: a new training programme.
PMID- 11005063
TI - The control of pain in palliative care.
PMID- 11005064
TI - The ethics of clinical research in developing countries.
PMID- 11005065
TI - The Academy of Medical Sciences.
PMID- 11005066
TI - Unravelling the heterogeneity of non insulin dependent diabetes.
PMID- 11005067
TI - Proteinuria in diabetes.
PMID- 11005068
TI - Clinical management of the painful diabetic neuropathies.
PMID- 11005069
TI - Diabetes in African Caribbean, and Indo-Asian ethnic minority people.
PMID- 11005070
TI - Principles of pain control in palliative care for adults. Guidance prepared by a
Working Group of the Ethical Issues in Medicine Committee of the Royal College of
Physicians.
AB - Specialist palliative care is now widely available and there are many good
textbooks of palliative medicine. But some patients still suffer pain needlessly.
Clinicians may not know how to use analgesia appropriately or may be anxious
about giving an adequate dose of strong opioids such as morphine. This brief
outline is intended to make the principles of pain control readily available to
all clinicians who look after terminally ill patients. It applies to patients
with non-malignant disease as well as to those with advanced cancer.
PMID- 11005071
TI - Discriminating for the ageing population--the positive approach.
PMID- 11005072
TI - Towards an improved career structure for non-consultant career grade doctors.
PMID- 11005073
TI - Imaging in medicine through the 20th century.
PMID- 11005074
TI - A new joint training programme in infectious diseases and medical microbiology.
AB - The increasing overlap between the disciplines of medical microbiology and
infectious diseases prompted the Joint Royal Colleges Committee on Infection and
Tropical Medicine to set up a working party to examine how trainees could obtain
certification in both subjects. Following widespread consultations, a scheme was
developed that entails six years of training and leads to the award of CCSTs in
both microbiology and infectious diseases. Both Royal Colleges and the Specialist
Training Authority have approved the scheme. Joint training will be demanding and
will not be suitable for everyone; it represents an alternative approach to
training in the infection disciplines that will run alongside the existing
monospecialty training programmes.
PMID- 11005075
TI - The potential role of IT in supporting the work of junior doctors.
AB - OBJECTIVES: To develop an information system using hand-held personal computers
to support the work of junior doctors. DESIGN: A user-driven design process was
used. Functionality reflected the core work of house officers (HOs) and senior
house officers (SHOs); i.e. ward round lists, immediate discharge summaries,
patient handover, laboratory and guidelines reference information and a personal
record of clinical experience. SETTING: Salford Royal Hospital NHS Trust is a
university hospital with a large acute medical case load. SUBJECTS: Several
'generations' of HOs and SHOs working in two of the four medical firms.
Predominantly acute medical case load. MAIN OUTCOME MEASURES: Robustness,
acceptability and benefits, assessed by observations and questionnaires. RESULTS:
The system has proved robust. It is time neutral for the juniors and minimal time
is needed for training/adaptation. Most felt the system to have either made their
lives easier or to have had no detrimental impact. Ward round lists and printed
immediate discharge summaries have been particularly successful. CONCLUSIONS: A
hand-held IT system designed for house doctors can provide immediate, low-cost
support for their activities.
PMID- 11005076
TI - Coping with pressures in acute medicine--the second RCP consultant questionnaire
survey.
AB - The second questionnaire survey of consultant physicians involved in acute
unselected takes in 1999 achieved a 76% response rate, and the results have been
compared with those from the first survey of 1997. The proportion of consultants
whose trainees worked partial shifts had increased from 42% to 61%, although
these patterns of duty were adjudged to have detrimental effects on the quality
and continuity of care, and on junior staff education and training. The benefits
of ward-based systems were counterbalanced by their disadvantages, but
introductions of admission wards and assessment units were considered a
resounding success. The number of hospitals with 'physician of the week' schemes
had increased from 12 to 23, but opinion of their value was sharply divided. The
provision and competence of all grades of locums was identified as an increasing
problem. Seventy per cent of respondents stated that they would never participate
in 'hands-on' emergency care, although 86% thought that future consultants might
have to do so. Seventy-nine per cent reported increases in the pressures of their
posts and in their working hours, and the tensions between general and specialist
duties were highlighted. Most consultants considered that the only long-term
solution to the staffing crisis was a marked expansion in the numbers of all
grades of medical staff.
PMID- 11005077
TI - Controversy in thyroid disease.
AB - Effective management for hypothyroidism has been available for a century, thanks
to the pioneering efforts of George Murray, who first tested injection of thyroid
gland extracts in Newcastle. Radioiodine for the diagnosis and then treatment of
Graves' hyperthyroidism was introduced by Hertz and Roberts in Boston, and by
Leblond in Paris, in 1943, the same year that Astwood in the USA began to use the
predecessors of modern antithyroid drugs. Despite this lengthy history, debate
continues as to the most effective management of these common disorders. More use
of radioiodine, including its use in euthyroid goitre, is being advocated as its
safety is now well established. Recent developments in optimising these
treatments will be considered in this brief review.
PMID- 11005078
TI - Virus hepatitis update.
AB - Currently seven viruses, A, B, C, D, E, G and transfusion transmitted virus
(TTV), are recognised in the hepatitis virus alphabet. Hepatitis G virus and TTV
probably do not cause liver disease in humans. Hepatitis A and E usually cause a
self-limiting hepatitis followed by complete recovery but occasionally cause
fulminant hepatic failure. Hepatitis B and C are major public health problems
worldwide due to their sequelae of chronic hepatitis, cirrhosis and primary liver
cancer. Chronic hepatitis C is a particular health issue for Western Europe
already, accounting for 40% of end-stage cirrhosis and 30% of liver transplants.
The contribution of hepatitis C to chronic liver disease is predicted to rise in
the future. Vaccines can prevent hepatitis A and B. Interferon alpha is effective
treatment in 25-30% of patients with chronic hepatitis B or C. The prospects for
treating chronic hepatitis B have been improved by the introduction of reverse
transcriptase inhibitors. Lamivudine is the first drug of this class to be
licensed. The optimal use of these new drugs is currently being studied. The
success rate for treating chronic hepatitis C can be raised to about 40% with
combination therapy of interferon alpha and ribavirin. A large research effort to
discover new antiviral agents against hepatitis C is already giving the prospect
of more effective therapies in the next few years.
PMID- 11005079
TI - Medicine in the millennium: confronting the issues.
AB - This joint conference of the Royal College of Physicians of London, the Royal
College of Surgeons of England and the Royal Society of Medicine took place on 1
November 1999 at the Royal Society of Medicine in London.
PMID- 11005080
TI - A NICE winter conference.
PMID- 11005081
TI - Insurance medicine.
PMID- 11005082
TI - The consultation in art.
PMID- 11005083
TI - Balzac and cretinism.
PMID- 11005084
TI - Alcohol abuse and the burden on the NHS.
PMID- 11005085
TI - The National Clinical Guidelines for Stroke.
PMID- 11005086
TI - Withdrawing and withholding life-prolonging medical treatment.
PMID- 11005087
TI - Health care cost in Africa.
PMID- 11005088
TI - [Surgery of the external auditory canal in familial bilateral auditory canal
atresia].
AB - BACKGROUND: Inherited isolated bilateral atresia of the external auditory canal
is rare. Ear canal surgery procedure is difficult. METHODS: Basing on a case
report of a family with inherited isolated bilateral atresia of the external
auditory canal in 4 cases the way of preoperative diagnostics including human
genetics and our surgical concept is described. RESULTS: Resulting clinical
findings showed complete epithelialization of the ear canal and ear drum with
slight conductive hearing loss. CONCLUSIONS: Canaloplasty in atresia can be
easily and successfully accomplished by our modified technique.
PMID- 11005089
TI - [Prediction of verbal and numerical comprehension in patients with cochlear
implants].
AB - BACKGROUND: Cognitive abilities determine the outcome of cochlear implantation.
Neuropsychological tests of intellectual, memory, attentional and emotional
functions were applied pre-operatively in 33 deaf patients receiving a cochlear
implant. The outcome of verbal and numerical comprehension was measured in a
subgroup of 14 patients post-operatively and correlated with pre-operative
neuropsychological performance. METHODS: Neuropsychological performance was
recorded using standardized tests for intellectual abilities (abbreviated
Wechsler Adult Intelligence Scale [WAIS], crystallized intelligence scale),
memory performance (Benton Visual Retention Test), attentional functions (d2
letter-cancellation-test), reaction time (Vienna Reaction Test) and emotional
state (personality inventories). Verbal and numerical comprehension was measured
post-operatively following adaptation of the speech processor. Performance and
comprehension data were correlated. RESULTS: Cognitive performance parameters did
not differ significantly from those of a healthy group. There was a correlation
of r = +0.65 between numerical comprehension and the "mosaic-test", a subtest of
the WAIS and of r = +0.78 between numerical comprehension and the crystallized
intelligence scale. CONCLUSIONS: Pre-operative cognitive parameters may predict
the outcome of cochlear implants.
PMID- 11005090
TI - [Differential diagnosis of sinugenic enophthalmos].
AB - BACKGROUND: Spontaneous enophthalmos without recent trauma is a rare condition.
Its origin is difficult to evaluate. METHOD: Specific properties of this symptom
complex are presented based on a literature review and on case reports. Possible
connections between enophthalmos and paranasal sinus diseases as well as
differential diagnoses are analysed. PATIENTS: 1. 31 year old female patient with
right spontaneous enophthalmos and no history of trauma. CT-imaging disclosed
tissue formation in the maxillary sinus, partially destroyed medial orbital wall
and floor, descended orbital contents following Caldwell-Luc procedure several
years previously. After endonasal surgery of ethmoidal and maxillary sinus with
removal of a large cyst good functional and cosmetical result. 2. 25 year old
male patient complaining of pain in the periorbital region, presenting with left
enophthalmos and superonasal deviation of the eyeball. MRI and CT revealed a
tumor in the orbital floor region with total destruction of the roof of the
maxillary sinus. Removal of the tumor by a combined lateral rhinotomy and
subciliary approach. DIAGNOSIS: Leiomyoma. Orbital reconstruction with PDS-sheet.
Postoperatively, improved globe position and motility. No recurrence during three
year follow-up. CONCLUSION: When evaluating the causes of enophthalmos, chronic
diseases of the paranasal sinuses or their walls must be considered. Surgical
therapy is promising.
PMID- 11005091
TI - [Long-term outcome of frontal sinus surgery: comparison of extranasal and
endonasal surgical techniques].
AB - BACKGROUND: During the last decades rhinosurgery largely developed up to
endonasal accesses. Meanwhile many of the new techniques are established, so that
the outcome of traditional extranasal methods should be compared with those of
endonasal accesses, in order to estimate the status and for critical
consideration. METHODS: A retrospective analysis recorded the results of 236
patients, operated on primary frontal sinus disease 1985-1993. The records were
consulted concerning inpatient treatment and outpatient aftercare during
standardized paranasal sinus consulting hours. RESULTS: During the follow-up
period (3-10 years) 8% of the patients underwent resurgery. The lowest revision
rate was found after using endonasal technique (5.9%), compared with osteoclastic
methods (Ritter-Jansen, Riedel: 10.6%). The domain of osteoplastic operations
with a revision rate of 9.4% were fractures, osteomas and mucoceles, because of
an impossible endonasal access. In decision on osteoclastic procedures, the
already osteoclastically operated site was of prime importance, especially since
1990. CONCLUSION: Already during the early years endonasal techniques of
paranasal sinus surgery showed better outcome than osteoclastic accesses. The
analysis indicates that the change to endonasal functional paranasal sinus
surgery is justified and should be kept up. The traditional methods still have
their rare authorization in case of special indications, especially if an
osteoclastic procedure has been carried out already.
PMID- 11005092
TI - [hBD-2 gene expression in nasal mucosa].
AB - BACKGROUND: Chronic sinusitis is one of the frequent inflammatory diseases and
has a complex pathogenesis. A substantial factor seems to be recurrent bacterial
infections. Pseudomonas aeruginosa (PA) frequently can be found in nasal smears
of patients with persistent sinus symptoms after sinus surgery. Lately a new
antimicrobial peptide of epithelial origin, human Beta-Defensin-2 (hBD-2), with a
strong antibacterial effect against PA could be identified within lesional skin
scales of patients suffering psoriasis. Aim of this study was to investigate hBD
2-mRNA expression in nasal cells and tissue. METHODS: Total RNA was extracted
from nasal polyps and turbinates following TRIzol protocol. Epithelial cells and
fibroblasts of nasal human tissue were isolated and cultivated. The cells were
stimulated with PA using different time points and different concentrations.
Total RNA was isolated as mentioned above, reverse transcribed and amplified in a
Semi-quantitative Reverse Transcriptase PCR (SQRT-PCR) with genespecific hBD-2
primers. RESULTS: PA induces time- and dose-dependently hBD-2 gene expression in
nasal epithelial cells. Unstimulated epithelial nasal cells were able to express
hBD-2 mRNA constitutively, whereas nasal fibroblasts showed no hBD-2 mRNA
expression. Nasal polyps showed a comparable less hBD-2 gene expression then
nasal turbinates. CONCLUSIONS: hBD-2 possibly mediates a specific, early starting
antimicrobial defense strategy of the nasal mucosa. This hypothesis would explain
persistent infections with PA through diminished hBD-2 gene expression.
PMID- 11005093
TI - [Neuronavigation in the region of the skull base].
AB - Neuronavigation (computer-aided surgery planning and performance) has proven to
be helpful in performing neurosurgical operations. The experiences of our
department gained on more than 500 patients operated upon will be presented, with
special focus on more than 100 operations for lesions on the skull base.
Navigation is one of several modern surgical tools, its value cannot be defined
without observing other improvements e.g. in the area of preoperative
diagnostics, intraoperative monitoring, microsurgical instruments and
microsurgical approaches.
PMID- 11005094
TI - [The joint capsule of the cricoarytenoid joint: biomechanical and clinical
aspects].
AB - BACKGROUND: Impaired movement of the cricoarytenoid joint with hoarseness and
immobility of the vocal ligament may occur as a consequence of laryngeal trauma
and joint disease. Little is known to date about the cricoarytenoid joint capsule
and its role in joint pathology. METHODS: The present study analyses the
structure of the cricoarytenoid joint capsule by means of histological,
immunohistochemical, and scanning electron microscopical methods. Investigations
are performed on larynges of 17 male and 16 female. RESULTS: The cricoarytenoid
joint was found to be lined by a wide and lax joint capsule consisting of a
fibrous and a synovial membrane. The capsule was strengthened posteriorly by the
cricoarytenoid ligament. As like the fibrous membrane the cricoarytenoid ligament
consisted mainly of collagen types I and III. Moreover the ligament was found to
be rich in elastic fibers. Unexpected large and intensively vascularized synovial
folds projected into the joint cavity. CONCLUSION: The capsule of the
cricoarytenoid joint can be compared with the joint capsules of the limbs despite
its structure and its involvement in joint pathology. Based on the laxity of the
joint capsule it was concluded that invasive interventions at the respiratory
tract with dislocation of the arytenoid cartilage can lead to incarceration of
the synovial folds. After a trauma aero-synovitis or formation of hemarthrosis
may occur, with subsequent fixation of the arytenoid in an abnormal position.
PMID- 11005095
TI - [Transoral treatment of severe laryngomalacia. Review and presentation of a
modified surgical technique].
AB - BACKGROUND: Laryngomalacia is the most common cause of stridor in children. So
far various authors have described surgical techniques in a sense of a
supraglottoplasty or an epiglottoplasty to handle the severe form of this
disease. We present a modified technique of the so called epiglottopexy. METHODS:
Under the different types of laryngomalacia this study focuses on the treatment
of three patients (5 to 10 months) with a posterior displacement of the
epiglottis during inspiration. The first step of our technique was to denude a
small portion of the base of the tongue from mucosa. A corresponding lesion was
created on the lingual surface of the epiglottis. The vaporisation of the mucosa
was performed with the CO2 laser at a power setting of 1 Watt and a 0.25 mm spot
size. The epiglottis was then fixed transorally to the base of the tongue with 2
single stitch sutures and 1 inverse mattress suture, using a resorbable material.
RESULTS: No intra- or postoperative complications were observed. All three
patients demonstrated a significant airway improvement without stridor.
CONCLUSION: The presented technique of transoral laser surgical epiglottopexy
seems to be a method suitable for the treatment of laryngomalacia caused by
posterior displacement of the epiglottis.
PMID- 11005096
TI - [Precancer stages of the oral mucosa: a review].
AB - According to the WHO collaborating centre precancerous lesions and precancerous
conditions have to be distinguished. Precancer: BACKGROUND: Erythroplakia is the
most dangerous precancerous lesion. It is rare, but may often remain undetected.
It will transform into cancer within five years and therefore, has to be excised
in every case. Leukoplakias show malignant transformation in 3-45% of the cases.
In spite of modern molecular biological and immunohistochemical techniques the
clinical appearance and the histological grading of the dysplasia are still most
important prognostic factors. Until 1992 every lesion showing signs of moderate
and severe dysplasia was excised in our department. Despite this treatment
strategy 6.2% of the leukoplakias (n = 161) transformed into cancer. Therefore,
we recommend to remove every lesion which does not disappear after eliminating
the etiological factors. METHODS: Since 1992 168 leukoplakias were completely
removed using the CO2 Laser and underwent histological examination. RESULTS: In
3% of these cases a carcinoma was detected in the leukoplakia; 5% of the lesions
recurred. Precancerous condition: The most important precancerous condition, the
oral lichen planus is treated in cases of erosive lesions only or if the patient
is suffering from the symptoms. Malignant transformation is seen in 1.5% of the
patients within 10 to 15 years. Histologically the oral lichen planus does not
differ from the oral lichenoid reactions, lesions in contact with amalgam
restorations mostly. In these cases a causative treatment with replacement of the
amalgam is recommended.
PMID- 11005097
TI - [Surgical and adjuvant drug therapy in head and neck cutaneous melanoma].
AB - The rapid incidence rise of cutaneous melanoma resulted in an increasing interest
in this particular tumor. During the last years public prevention campaigns
enlarged the awareness of melanoma, subsequently as a direct effect the mean
tumor thickness of melanoma, the most predictable prognostic factor, decreased.
Moreover, the biology of melanoma initiation and metastasis has been studied
extensively with special interest in molecular biology. Controlled clinical
studies answered several critical questions in respect to the standard care of
surgery in melanoma. Yet, the guidelines for the surgical treatment of head and
neck melanoma are in accordance to that of other localisations with reduced
safety margins around the primary tumor. Elective (prophylactic) lymph node
dissection (ELND) of regional lymph nodes is no more considered as a standard
tool. Moreover, ELND has been given up by most melanoma centers, since it is
known that prospective-randomized trials were not able to demonstrate an increase
of overall survival for patients with ELND compared with untreated patients.
Instead of this potentially aggressive treatment modality the examination of the
first draining regional lymph node, sentinel node biopsy (SNB), has been
introduced some years ago. Recently, a large clinical trial demonstrated that the
SNB status reflects the most valuable prognostic factor for primary melanoma
known so far. First studies in head and neck melanoma figured out that this
technique is more complex in this special localisation, but produced comparable
results. Systemic adjuvant (prophylactic) therapy of high-risk melanoma should
preferentially be applied within controlled clinical trials. Most attractive
candidates for an effective treatment are interferons. Several studies ruled out
that interferon alpha-treated melanoma patients demonstrate an extended disease
free survival. Adjuvant chemotherapy has not shown a clinically relevant benefit.
Thus, patients should preferentially be treated within controlled clinical
trials.
PMID- 11005098
TI - [Analysis of the p53 gene status of lymph node metastasis in the head and neck
region in occult primary cancer].
AB - BACKGROUND: Lymph node metastasis in the head and neck region with occult primary
cancer are a fairly rare tumor entity in head and neck cancer. Tumor biological
parameters as well as mechanism and cause for the development of this so called
"cancer of unknown primary" (CUP) are not well investigated in head and neck
cancer. Mutations of the p53 tumor suppressor gene are the most prevalent genetic
alteration of human malignancies and show an incidence of up to 50% in head and
neck cancer. For a further tumor biological definition of CUP the p53 status was
determined. METHODS: Twenty-three archival formalin fixed paraffined CUP of an
occult squamous cell carcinoma of the head and neck region were examined. In all
cases a primary cancer was never diagnosed. The DNA extracted from the tumor
material was amplified with specific primers for exon 4-9 of the p53 gene and
subsequently sequenced. RESULTS: None of the 23 CUP cases showed a mutation or
polymorphism in exon 4-9 of the p53 gene. CONCLUSIONS: The total absence of p53
mutations in the so called mutational "hot spots" shows a significant difference
to the frequency of primary tumors of the head and neck region. May be this tumor
biological characterisation helps to further elucidate the growth behaviour of
CUP in the head and neck region and the reason for their development.
PMID- 11005099
TI - [Detection of overexpression of insulin receptor gene in laryngeal carcinoma
cells by using differential display method].
AB - BACKGROUND: The insulin receptor (IR) is an essential protein localized on the
surface of almost all cell types. IR belongs to the tyrosine-kinase growth factor
receptor family. Insulin mediates proliferative responses in a variety of tumor
cells, however, the role of the IR molecule in carcinogenesis has not yet exactly
been established. METHODS: Messenger RNA from mucosal keratinocytes and laryngeal
carcinoma cells were transcribed in cDNA using reverse transcriptase and
amplified by PCR by means of a number of oligonucleotides. PCR products were
analyzed electrophoretically. RESULTS: Comparing the electrophoretic pattern of
both cell types the overexpression of a 127 bp fragment could be detected in
laryngeal carcinoma cells in contrast to benign keratinocytes. Cloning and
sequencing this fragment exact homologous match was found with exon-2 of the IR
gene. The overexpression of the IR gene in laryngeal carcinoma cells was
confirmed by Northern hybridization. CONCLUSIONS: The results show up-regulation
of IR-mRNA in laryngeal carcinoma cells suggesting that the number of IR is
enhanced in these cells. Hence it follows, that the overexpression of IR plays a
possible role in laryngeal cancer initiation and/or progression.
PMID- 11005100
TI - [Feeding of patients with ENT diseases using an enteral tube system (PEG/PEJ
tubes). A review].
AB - In patients with benign or malignant diseases of the larynx/pharynx causing
inadequate oral food intake, maintenance of individual adequate enteral nutrition
is a major medical goal. This is particularly important in patients with
malignant ENT tumours, where therapeutical measures as radiation or chemotherapy
result in further deterioration of nutritional status and consecutively of
quality of life and tolerance of therapy. Due to its safe and technically simple
route of placement, the PEG has become the preferred enteral route of choice for
enteral long-term nutrition world-wide. The technical success rate is > 99% with
a procedure-related lethality rate of about 0%. Prospective clinical studies
prove the excellent individual subjective acceptance of this method by patients.
Indications, contraindications, complications, technical procedures and clinical
aspects of PEG placement are described in detail in the present review. Long-term
enteral feeding via PEG is accepted as a safe, effective, easy to practise and
highly acceptable method with excellent long-term results and thus distinct
improvement of nutritional status. Individual decision for PEG placement should
be considered much earlier and more frequently in appropriate patients to save
and further improve clinical and nutritional status and consecutively quality of
life.
PMID- 11005101
TI - [The interesting case No. 36. Fibrous dysplasia of the temporal bone
(osteodystrophia fibrosa Jaffe-Lichtenstein)].
PMID- 11005102
TI - [Plastic reconstructions in the neck region. Neck surface soft tissue and skin
defects. I].
PMID- 11005103
TI - Use of an emboli containment and retrieval system during percutaneous coronary
angioplasty in native coronary arteries.
AB - BACKGROUND: Prevention of distal embolisation during percutaneous coronary
revascularisation may be necessary to reduce postinterventional morbidity and
mortality. METHODS AND RESULTS: We employed a newly developed emboli containment
and retrieval system in native coronary arteries during percutaneous coronary
angioplasty and stenting in 39 selected patients (mean age 58.9 +/- 10.1 years,
11 females) presenting with acute (n = 22; 8 LAD, 3 LCX, 11 RCA), subacute (n =
7; 2 LAD, 2 LCX, 3 RCA) or chronic (n = 6; 2 LAD, 4 RCA) total or subtotal
occlusion of an infarct-related vessel, or with severe stenosis and symptoms of
unstable angina (n = 4; 2 LAD, 2 RCA). Protection device-assisted angioplasty
with stent implantation was uneventful in all patients with good angiographic
results and normal postprocedural flow. Intermittent aggravation of anginal pain
during inflation of the occlusive balloon (from 2.5 to a maximum of 25 minutes
cumulative inflation time) was observed in 19 of the 36 conscious patients (7
with acute, 7 with subacute and 3 with chronic occlusion, and 2 with unstable
angina), but caused neither interruption of distal occlusion nor haemodynamic
instability. In 31 patients the aspirates contained visible debris. Histological
analysis showed particles up to 12 mm in size, consisting of necrotic core,
inflammatory cells, cholesterol debris, and old and fresh thrombi. In 8 patients
the aspirated particles were too small to allow microscopic diagnosis or debris
was absent. CONCLUSIONS: This preliminary report demonstrates the feasibility of
using a protection device in native coronary arteries to prevent distal
embolisation of particulate matter that is mobilised during percutaneous
interventions. To the extent that this material contributes to the mechanisms of
distal embolisation, noreflow and infarction, this device may help to reduce such
complications. Appropriately designed trials are required to assess the clinical
benefit of this system.
PMID- 11005104
TI - [Cost-effectiveness of primary PTCA and thrombolysis in the treatment of acute
myocardial infarction].
AB - Clinical studies have shown a favourable outcome for primary PTCA compared with
thrombolysis in the treatment of acute myocardial infarction. No data are
available in Switzerland on the logistic and economic implications of treating
more acute myocardial infarction patients by PTCA. The present paper sets out to
assess all published studies comparing the cost-effectiveness of the two
treatment modalities. A Medline search identified seven original cost and cost
effectiveness studies conducted between 1989 and 1999. According to these studies
emergency PTCA generates costs similar to thrombolysis in the treatment of acute
myocardial infarction if the infrastructure is available and there is high volume
output. Better clinical results, as suggested by the literature, would result in
a favourable cost-effectiveness ratio for primary PTCA.
PMID- 11005105
TI - Manifold manifestations of ergotism.
AB - Vasospastic side effects leading to organic manifestations are rare in ergotamine
therapy. To our knowledge, combinations of more than two signs of ergotism have
rarely been described in the literature so far. We present a 65-year-old male
patient who as a consequence of severe migraine had developed ergotamine abuse.
He was admitted to our hospital after one week of increasing abdominal pain.
During laparotomy, necrotic areas of the small intestine and the sigmoid colon
were resected, which on histopathologic examination revealed severe hypertrophy
of the smooth musculature of mesenteric arteries, resulting from chronic
vasospasms. Postoperatively, the patient developed ischaemia of the limbs which
was confirmed by angiography. Before death, the patient also showed ischaemic
signs in the acrae and necrosis of the tongue.
PMID- 11005106
TI - [Cholesterol and stroke risk: a role for statins?].
AB - Atherosclerosis is the most common cause of vascular diseases, but the relevance
of cholesterol has only been definitely associated with coronary artery disease
and peripheral vascular disease. In comparison, the role of cholesterol in stroke
is, while a tempting assumption, subject to controversy in the literature. The
crucial question--is cholesterol a risk factor for stroke?--remains open. Recent
trials with statin drugs, such as 4 S, CARE, LIPID and WOSCOP, have created a new
wave of enthusiasm by showing decreased risk of stroke in the statin-treated
patients. However, these trials are most often designed for patients with a known
history of coronary artery disease. In contrast, studies investigating the impact
of statins in the secondary prevention of stroke are still lacking. Moreover, the
beneficial effects of statins on clinical events may involve non-cholesterol
mechanisms. In regard to stroke prevention, there is no absolute evidence to
recommend the use of statin drug therapy.
PMID- 11005107
TI - [Tropical air in Zurich].
PMID- 11005108
TI - [Reference: Franke C. Value of radiosynovectomy in rheumatology and orthopedics].
PMID- 11005109
TI - Should sonographic screening for fetal Down syndrome be applied to low risk
women?
PMID- 11005110
TI - Assessment of hemodynamics using Doppler ultrasound.
PMID- 11005111
TI - The frequency of the detection of fetal echogenic intracardiac foci with respect
to maternal race.
AB - OBJECTIVE: To determine if there is a racial difference in the frequency of
identification of echogenic intracardiac foci (EIF) seen sonographically in the
hearts of second-trimester fetuses. METHODS: Over a 2-month period (June 1998
August 1998), all fetuses scanned between 15 and 20 completed weeks' gestation
were evaluated prospectively for the presence or absence of EIF. Pregnancies
specifically referred for the presence of EIF were excluded. The sonographer
performing the scan indicated maternal race as Asian, black, white, or (if
maternal race was not clear) unknown. Maternal race, gestational age, and the
presence or absence of EIF were prospectively documented. Follow-up of those
fetuses with EIF was obtained from the referring physicians' offices. The groups
were compared with respect to maternal race and presence or absence of EIF.
RESULTS: There were 46, 34, 400, and nine fetuses of the Asian, black, white, and
unknown mothers, respectively. The mean gestational age +/- 1 SD at examination
was 18.2 +/- 1.6, 17.5 +/- 1.4, 17.7 +/- 1.5, and 17.8 +/- 1.1 weeks, for the
Asian, black, white, and unknown mothers, respectively. The incidence of
sonographically detected EIF was 30.4, 5.9, 10.5 and 11.1% for the Asian, black,
white, and unknown mothers, respectively, P = 0.001. In a multivariate logistic
regression model, Asian mothers had an odds ratio of 3.8 (95% CI, 1.8, 7.6) for
having a fetus identified as having EIF, as compared with white mothers.
CONCLUSIONS: The Asian patient is more likely than patients of other races to
have a fetus with identified EIF. The counseling implications for Asian mothers
undergoing midtrimester sonography when EIF is identified should be tempered, due
to the increased frequency of EIF as a normal finding in the Asian population.
PMID- 11005112
TI - Color Doppler imaging in the diagnosis and management of chorioangiomas.
AB - Color Doppler imaging was used to investigate nine consecutive cases of placental
tumors referred for evaluation to a tertiary referral unit. Gray-scale ultrasound
findings were of a chorioangioma which was subsequently confirmed on pathologic
examination. On color Doppler imaging (CDI), three tumors appeared avascular and
the pregnancies were uncomplicated, two had only a few vessels in their
periphery, and four contained numerous vessels. These vascular chorioangiomas
were complicated by polyhydramnios and premature labor (n = 3), isolated
polyhydramnios (n = 1), fetal growth restriction (n = 1) and generalized non
immune fetal hydrops (NIHF) (n = 1). The maximum diameter of the tumors ranged
between 3 and 10 cm. There was no direct association between the size and
location of the tumor and the development of complications. Successful
amnioreduction was performed in the three cases of polyhydramnios and premature
onset of labor. Vascular sclerosis was attempted unsuccessfully in the case
complicated by severe NIHF. Our data indicate that the vascularization of the
tumor is a pivotal determinant factor of pregnancy outcome. Where the tumor is
avascular, no specific complications should be expected. Where the tumor is
vascularized, and in particular if it contains numerous large vessels, serial
ultrasound and Doppler examinations are warranted to detect polyhydramnios and
early features of fetal congestive heart failure.
PMID- 11005113
TI - The coronary sinus in the fetus.
AB - INTRODUCTION: The normal coronary sinus drains venous blood from the cardiac
veins to the right atrium. In some instances, the coronary sinus may be dilated
due to volume or more rarely pressure overload. AIMS: To assess the feasibility
of detecting the coronary sinus in the fetus and to establish the normal values
of the coronary sinus dimensions throughout gestation. SUBJECTS AND METHODS:
Fetal echocardiography was performed in 78 normal fetuses from the 16th to the
40th week of gestation (median 25 week). The coronary sinus was measured in four
chamber view (87% of cases) or in parasternal short axis view equivalent (13%). A
second group of nine fetuses with a dilated coronary sinus was compared to the
normal group. RESULTS: Adequate imaging of coronary sinus was obtained in 97.4%
of the normal fetuses. The diameter of the coronary sinus ranged from 1 to 3.2 mm
(2 mm +/- 0.13 mm, mean +/- 5% confidence interval) and correlated well with the
age of pregnancy (r = 0.86). The length-to-diameter ratio of 24% (+/- 6%) did not
vary throughout pregnancy. All nine fetuses with a dilated coronary sinus had a
persistent left superior vena cava which drained into it. The diameter of the
coronary sinus was approximately three times larger in the abnormal group with a
diameter-to-length ratio of approximately 83% (P < 0.0001). CONCLUSION: The
coronary sinus is readily identified in the fetus. It gradually increases during
pregnancy. An abnormal coronary sinus is easily diagnosed and should prompt the
sonographer to look for a persistent left superior vena cava.
PMID- 11005114
TI - Routine ultrasound fetal examination in pregnancy: the 'Alesund' randomized
controlled trial.
AB - OBJECTIVE: To evaluate the possible benefits of the routine use of ultrasound
screening in pregnancy. DESIGN: A randomized controlled trial was designed to
detect a 50% difference in the incidence of induction for apparent post-term
pregnancies between women who were screened with ultrasound and unscreened women.
A total of 1628 pregnant women from the general population were included. Eight
hundred and twenty-five were allocated to an ultrasound examination at the 18th
and 32nd week of pregnancy in addition to receiving routine antenatal care. The
remaining 803 women received standard antenatal care, but could only be referred
for ultrasound examination on clinical indication. RESULTS: The incidence of
induced labor due to apparent post-term pregnancies was approximately 70% lower
in the ultrasound-screened group. Inductions from all causes were also less
frequent among ultrasound-screened women. There were six perinatal deaths among
the screened and seven among the controls after excluding three lethal
malformations among the controls. There was no difference in Apgar score after 1
min, but the proportion with Apgar score less than 8 after 5 min was lower among
the screened group (P = 0.04). The need for positive pressure ventilation for
more than 1 min was lower among the screened group (P = 0.02). Birth weight was
slightly higher in the screened group (39 g), but the difference was not
statistically significant. Among the controls three pairs of twins remained
undiagnosed until the mothers were admitted to the hospital in labor at between
36 and 38 weeks gestation. CONCLUSION: These results suggest that for women who
were screened with ultrasound, obstetricians were less likely to induce labor due
to apparent post-term pregnancy, than for women who were not screened. All 10
pairs of twins in the screened group were diagnosed at the routine examination.
These data also suggest that perinatal morbidity might be slightly lower in the
screened group.
PMID- 11005115
TI - Human fetal pulmonary artery velocimetry: repeatability and normal values with
emphasis on middle and distal pulmonary vessels.
AB - OBJECTIVES: To establish the nature and gestational age dependency of flow
velocity waveforms from fetal middle and distal arterial pulmonary branches in
the second half of normal pregnancy and to determine repeatability and inter
relationship of flow velocity waveform recordings from proximal, middle and
distal arterial pulmonary branches. DESIGN: Cross-sectional study.
SUBJECTS/METHODS: A total of 111 singleton normal pregnancies between 20 and 40
weeks of gestation were studied using a color-coded Doppler ultrasound system.
Pulmonary waveforms were obtained at the level of the fetal cardiac four-chamber
view. Repeatability was tested from two recordings at 15 min time-intervals in 25
separate normal pregnancies. RESULTS: Acceptable repeatability of flow velocity
waveforms from fetal arterial pulmonary branches was established with
coefficients of variation below 15%. The nature of middle arterial pulmonary flow
velocity waveforms was similar to that of proximal waveforms and showed a
gestational age-related change for diastolic velocity parameters, peak
systolic/peak diastolic ratio and pulsatility index. The distal arterial
pulmonary branch displayed a monophasic forward flow velocity profile throughout
the cardiac cycle. All velocity parameters of the distal branch remained
unchanged with advancing gestation, with the exception of the pulsatility index.
Significant inter-pulmonary changes were found for all pulmonary arterial
waveform parameters. CONCLUSIONS: Alteration in pulmonary vascular resistance may
play a role in gestational age-related changes, whereas changes in vessel
branching/diameter and in the distance between the heart and more distal arterial
pulmonary vessels may cause inter-pulmonary differences.
PMID- 11005116
TI - Maternal cardiac systolic and diastolic function: relationship with
uteroplacental resistances. A Doppler and echocardiographic longitudinal study.
AB - OBJECTIVE: To test the hypothesis of the existence of a relationship between
central and peripheral hemodynamic parameters by the longitudinal evaluation of
maternal echocardiographic and uteroplacental resistance modifications during
normal pregnancy. METHODS: Forty-three healthy normotensive primigravidae were
evaluated at 12 +/- 1, 21 +/- 1, and 33 +/- 1 weeks of gestation with uterine
artery color Doppler and maternal echocardiographic examinations to identify
morphologic, systolic, and diastolic variables. RESULTS: Cardiac output and
stroke volume significantly increased during pregnancy. Uterine resistance index
(RI) decreased from the first to the second trimesters (0.72 +/- 0.10 versus 0.54
+/- 0.09, P < 0.001). Left atrial dimensions increased during pregnancy (33.8 +/-
1.9 cm, 38.1 +/- 1.8 cm, 39.3 +/- 2.1 cm, P < 0.001). Left atrial function also
increased. Left ventricular mass increased (132 +/- 18 g, 162 +/- 16 g, 174 +/-
27 g, P < 0.001). Diastolic function parameters showed significant modifications:
E wave velocity and E/A ratio decreased; A wave velocity and deceleration time of
the E wave (DtE) increased; the left ventricular isovolumetric relaxation time
(IVRT) decreased significantly (88.7 +/- 6.7 ms, 75.6 +/- 7.7 ms, 71.1 +/- 5.0
ms, P < 0.001) showing a correlation with left atrial dimensions and RI (r =
0.38, r = 0.47, respectively; P < 0.001). CONCLUSIONS: Diastolic cardiac function
varies during pregnancy. A relationship between preload (left atrial
enlargement), afterload (RI reduction), morphologic, and diastolic function
modifications (IVRT reduction, DtE prolongation) appears to exist as a
consequence of the hemodynamic modifications which occur during physiologic
pregnancy. Diastolic function analysis maybe useful to identify women who fully
adapt to pregnancy, and to understand the mechanisms that might be involved in
women who show abnormal uterine artery Doppler waveforms.
PMID- 11005117
TI - The influence of maternal exercise on placental blood flow measured by
Simultaneous Multigate Spectral Doppler Imaging (SM-SDI)
AB - OBJECTIVE: To evaluate the effect of maternal isometric exercise on the placental
blood flow as reflected by the velocimetric indices PI and RI derived from
placental arteries. SUBJECTS: Thirty-four healthy women with normal singleton
pregnancies between 22 and 35 weeks of gestation. METHODS: All subjects underwent
an isometric handgrip exercise test. Maternal blood pressure and heart rate
together with placental PI and RI were measured at rest, during the exercise and
in the post-exercise recovery phase. All Doppler measurements were obtained using
the Simultaneous Multigate Spectral Doppler Imaging (SM-SDI) technique, a new
ultrasound modality that enables a Doppler study of multiple locations to take
place within a very short time. RESULTS: There was a significant increase in the
mean values of the maternal blood pressure and heart rate during the exercise and
a significant decline in the recovery phase. There was no significant change in
the mean values of the Doppler indices throughout the examination. CONCLUSION:
Isometric handgrip exercise test during pregnancy does not affect the impedance
of the placental circulation.
PMID- 11005118
TI - Non-invasive assessment of endothelial function in normal pregnancy.
AB - OBJECTIVE: To assess endothelial function in normal pregnancy by non-invasive
methods. METHODS: Flow-mediated dilatation of the brachial artery was measured by
ultrasonography in 157 women with normal singleton pregnancies between 10 and 40
weeks' gestation and 19 non-pregnant controls. RESULTS: Flow-mediated dilatation
in the non-pregnant controls was 6.42 +/- 2.45%. In pregnant women, between 10
and 30 weeks, the mean flow-mediated dilatation (8.84 +/- 3.18%) was
significantly higher than the non-pregnant controls (P = 0.002), but after 30
weeks of gestation there was a decrease to prepregnancy levels. Resting vessel
diameter and blood flow were significantly increased in pregnancy, mainly after
30 weeks' gestation (P < 0.001, P < 0.001, respectively). Flow-mediated
dilatation was significantly correlated to resting vessel diameter and reactive
hyperemia. CONCLUSION: Normal pregnancy is associated with enhanced endothelial
function which is apparent from at least 10 weeks' gestation.
PMID- 11005119
TI - Automated cardiac output measurements by ultrasound are inaccurate at high
cardiac outputs.
AB - OBJECTIVE: The sonographic technique of automated cardiac output measurement
(ACM) is a promising new method to measure cardiac output and could be of use in
a high-risk obstetric unit in the treatment of pre-eclamptic patients. The aim
was to determine the accuracy of the ACM method. DESIGN: Comparative study of the
sonographic technique of ACM versus cardiac output measured by thermodilution
(TD). METHODS: The study included 39 intensive care patients, 21 men, 13 non
pregnant women and five severely pre-eclamptic pregnant patients, with a wide
range of cardiac outputs, in whom TD catheters had been inserted for clinical
reasons. Two separate experienced observers, blinded to the results obtained with
the other method, performed four successive measurements in each patient with
either the ACM or TD technique. The averaged cardiac output value per patient and
method was used for comparison. RESULTS: Cardiac output was successfully measured
with ACM and TD in 85 and 100% of patients, respectively. Mean cardiac output
measured by ACM (6.77 +/- 1.90 L/min) was significantly lower than that measured
by TD (9.12 +/- 3.06 L/min). Although cardiac output values obtained with ACM
were significantly correlated with those measured by TD, the ACM values were
consistently lower than TD values in the higher cardiac output range; the
relationship was represented by ACM = 0.35 TD + 3.55 L/min (r = 0.57, P < 0.001).
The (ACM - TD) difference increased significantly with cardiac output, through a
difference in stroke volume, not in heart rate. CONCLUSION: The ACM is not an
accurate tool to measure cardiac output in patients with a high cardiac output,
including treated pre-eclamptic women.
PMID- 11005120
TI - The effect of methyldopa on retinal artery circulation in pre-eclamptic gravidae.
AB - OBJECTIVE: To evaluate the effect of methyldopa on retinal artery circulation in
pre-eclamptic gravidae using color Doppler imaging and spectral analysis.
METHODS: Fifty-three pre-eclamptic singleton gravidae of gestational age greater
than 22 weeks were examined. Patients with sustained hypertension after 1-2 days
hospital rest were treated with oral antihypertensive medication, 250-500 mg
methyldopa, three to four times a day for a minimum of 5-7 days. The right
central retinal arteries were insonated and Doppler waveform values were analysed
before and after medication. RESULTS: The change of the maternal heart rate after
methyldopa treatment was -3.96 +/- 7.88 beats per min (P = 0.0006). The change of
fetal heart rate was not significantly altered. The change of the diastolic
arterial blood pressure after treatment was -4.19 +/- 12.36 mmHg (P = 0.0169). In
36 gravidae, in whom hypotensive effects were noted after treatment with
methyldopa, the increase in peak velocity, end-diastolic velocity and mean
velocity of the retinal artery were 2.41 +/- 2.20 (P < 0.0001); 1.48 +/- 1.23 (P
< 0.0001) and 1.70 +/- 1.42 (P < 0.0001), respectively. The decrease in
pulsatility index of the retinal artery after treatment with methyldopa was -0.17
+/- 0.22 (P < 0.0001). In the remaining 17 gravidae, in whom no hypotensive
effects were noted after treatment with methyldopa, the decrease in end-diastolic
velocity and mean velocity were -1.50 +/- 1.70 (P = 0.0022) and -0.98 +/- 1.90 (P
= 0.0488), respectively. The increase in pulsatility index was 0.34 +/- 0.30 (P =
0.0003). CONCLUSIONS: In pre-eclamptic gravidae in whom the hypotensive effects
were noted after treatment with methyldopa, the mean velocity of the retinal
arteries was significantly higher and the mean pulsatility index lower after
treatment. We conclude that the hypotensive effect of methyldopa in pre-eclamptic
gravidae is associated with a significant decrease in retinal artery vascular
resistance.
PMID- 11005121
TI - The influence of fetal position on nuchal translucency thickness.
AB - OBJECTIVE: To determine whether nuchal translucency thickness is influenced by
the fetal position at ultrasound examination. SUBJECTS: Transabdominal ultrasound
examination for pregnancy dating and measurement of nuchal translucency thickness
was performed at 10-14 weeks' gestation in all women attending the antenatal
clinic of our hospital. During the examination special attention was paid to a
change in fetal position from prone to supine or vice versa. METHODS: For each
fetus the nuchal translucency measurement was repeated when a positional change
from prone to supine or vice versa was recorded. All measurements were recorded
on hard copy. An image-scoring method was used and evaluated by three independent
reviewers. RESULTS: Eighty-five fetuses were included in this study. The mean
nuchal translucency for supine fetuses was 1.91 mm compared with 1.93 mm for
prone fetuses. The mean quality-score was 6.54 for supine fetuses and 6.55 for
prone fetuses. This difference was not statistically significant. CONCLUSION:
Fetal position has no influence on the measurement of nuchal translucency.
PMID- 11005122
TI - Sonographic visualization of normal-size ovaries during pregnancy.
AB - OBJECTIVE: To assess the ability of ultrasound to detect ovaries of normal size
during pregnancy METHODS: A prospective study of 329 women with a normal
pregnancy course was undertaken; 68 were excluded from analysis because of an
enlarged, cystic ovary. Of the remainder, 60 pregnancies were examined in the
first trimester and 201 in the second or third trimester. The first group
underwent transvaginal (TVS) and transabdominal (TAS) scanning. The second group
underwent TAS examination only. RESULTS: In the first-trimester group, TVS
identified both ovaries in 57 patients (95%) and transabdominal ultrasound in 20
(33.3%). In the second- and third-trimester patients, TAS visualized both ovaries
in 33 patients (16.4%), and neither ovary in 120 (59.7%). Both ovaries were less
visible with advancing gestational age. The right ovary showed a significant
change in position during pregnancy, from about 1 cm (at 15-24 weeks) to 2.5 cm
(at 30-41 weeks) cranial to the iliac spine. The left ovary was found 1 cm above
the iliac spine throughout pregnancy. CONCLUSIONS: Transvaginal sonography is
adequate for the visualization of both ovaries in the first trimester of
pregnancy. With advanced gestational age, the ovaries were significantly less
visible by TAS. Sonographic scanning of the ovaries in second and third trimester
should be concentrated mainly at the level of the iliac spine. Poor sonographic
visualization of both ovaries in late gestation may mandate the use of other
imaging modalities.
PMID- 11005124
TI - Increased fetal nuchal translucency: possible association with esophageal
atresia.
AB - We describe a case in which in-utero diagnosis of an esophageal atresia with a
tracheo-esophageal fistula in the third trimester followed the finding of an
increased nuchal translucency in the first trimester and suggest a mechanism by
which these two findings might be associated.
PMID- 11005123
TI - Uterine artery impedance to blood flow on the day of embryo transfer does not
predict obstetric outcome.
AB - OBJECTIVE: To evaluate the influence of uterine artery impedance to blood flow on
the day of embryo transfer for prediction of early pregnancy loss and obstetric
outcome. METHODS: The uterine artery pulsatility index (PI) and resistance index
(RI) were evaluated prospectively by transvaginal Doppler in 102 infertile women,
who conceived as the result of fresh or frozen embryo transfer. Uterine artery
impedance to blood flow was compared to the obstetric outcome. RESULTS: The 111
treatment cycles studied resulted in 31 spontaneous abortions, four ectopic
pregnancies, and 76 deliveries. There were no differences in uterine artery PI
and RI (mean +/- SD) between cycles resulting in normal delivery (2.69 +/- 0.71
and 0.88 +/- 0.06) and those resulting in spontaneous abortion (2.71 +/- 0.67 and
0.88 +/- 0.05) or ectopic pregnancy (2.36 +/- 0.54 and 0.85 +/- 0.06). There were
no differences in PI and RI between uncomplicated singleton pregnancies (2.74 +/-
0.78 and 0.88 +/- 0.06) and those developing intra-uterine growth restriction
(IUGR), pregnancy-induced hypertension (PIH), or preterm birth (2.54 +/- 0.47 and
0.87 +/- 0.04, pooled data). CONCLUSIONS: Uterine artery PI and RI on the day of
embryo transfer were unrelated to the risk of the pregnancy ending in spontaneous
abortion or ectopic pregnancy. These values were of no value in the prediction of
IUGR, PIH or preterm birth.
PMID- 11005125
TI - Diagnosis of a fetal mesoblastic nephroma by 3D-ultrasound.
AB - We report a case of a fetal renal tumor detected prenatally on 3D-ultrasound. As
the lesion was well encapsulated the initial sonographic diagnosis was that of a
nephroblastoma. Volume calculation by the 3D technique gave a reliable estimation
of the tumor size. Contrary to all published case reports concerning antenatally
diagnosed mesoblastic nephromas, there was no polyhydramnios. Elective delivery
was performed by Cesarean section at 38+ weeks gestation. The neonate underwent
left nephrectomy on the second day of life. The subsequent course was uneventful
without recurrence of the tumor.
PMID- 11005126
TI - Klippel-Trenaunay-Weber syndrome presenting as massive lymphangiohemangioma of
the thigh: prenatal diagnosis.
AB - We report a case of Klippel-Trenaunay-Weber syndrome presenting prenatally as a
massive congenital lymphangiohemangioma of the thigh. Routine ultrasonographic
examination revealed multiple distorted cystic areas extending from the right
flank through the right lower extremity of a 30-week fetus. A diagnosis of cystic
lymphangioma of the thigh was suspected prenatally. Neonatal evaluation confirmed
the prenatal findings. Neonatal color Doppler imaging revealed blood vessels
within the tumor. The differential diagnosis is discussed together with available
therapeutic procedures.
PMID- 11005127
TI - Acute bowel perforation in a fetus with gastroschisis.
AB - Gastroschisis is a congenital anomaly with a reported incidence of 1 in 10,000
live births. Although prenatal diagnosis is more common with the widespread use
of biochemical markers and obstetric ultrasound, the role of ultrasound in the
identification of the fetus that might need early intervention has not been
established. Acute bowel perforation was diagnosed by ultrasound at 34 weeks
gestation in a fetus with gastroschisis. An immediate Cesarean section was
performed, followed by repair with primary closure. The neonatal outcome was
favorable. The post-partum findings, including bowel pathology, confirmed the
antenatal diagnosis. Acute bowel perforation can be diagnosed antenatally.
Immediate intervention, before further bowel injury occurs, might enhance the
ability of the surgeon to perform primary closure and obtain a favorable outcome.
PMID- 11005128
TI - Prenatal sonographic features of vesicoallantoic cyst.
PMID- 11005129
TI - Ultrasound--frequently asked questions.
PMID- 11005130
TI - Intrapericardial teratoma.
PMID- 11005131
TI - [Human amniotic fluid transferrin stimulates progesterone production by human
trophoblast cells in vitro].
AB - OBJECTIVE: During pregnancy transferrin plays a key role as an iron transport
protein to serve the increased fetal demands of iron. Transferrin is also present
in relatively high concentrations in amniotic fluid [6], showing a different
glycosylation compared with serum transferrin. The biological function of human
amniotic fluid transferrin (hAFT) is still unknown. In addition trophoblast cells
also synthesise transferrin. Transferrin synthesised by the trophoblast shows a
special glycosylation. We found identical carbohydrate structure of hAFT and
trophoblast transferrin. We investigated the influence of hAFT on the
progesterone-, cortisol- and hCG-release of trophoblasts in culture compared with
the influence of human holo- and apo-serum transferrin on the release of these
hormones. MATERIAL AND METHODS: Cytotrophoblast cells were prepared from human
term placentae by standard trypsin-DNAse dispersion of villous tissue followed by
a percoll gradient centrifugation step. When placed in culture, the trophoblasts
were incubated with varying concentrations (50-300 micrograms/ml) of human
amniotic fluid- and serum-transferrin. Unstimulated cells of each placenta used
as controls. Culture supernatants were assayed for progesterone, hCG and cortisol
by enzyme-immunometric methods. RESULTS: Our results show, that the release of
progesterone increased in hAFT-treated cell cultures compared to untreated cell
cultures. Holo- and apo-serumtransferrin did not show any effect on the
progesterone release by trophoblast cells in vitro. Neither hAFT nor holo- and
apo-serum transferrin had any effect on the cortisol- and hCG-release in vitro.
CONCLUSIONS: Progesterone is a marker for differentiation of trophoblasts in
syncytiotrophoblasts. Only hAFT stimulates the progesterone production. We
suggest, that hAFT can modulate the endocrine function of trophoblast cells in
culture by regulating progesterone production.
PMID- 11005132
TI - Determination of cytokine mRNA-expression in term human placenta of patients with
gestational hypertension, intrauterine growth retardation and gestational
diabetes mellitus using polymerase chain reaction.
AB - OBJECTIVE: Our objective was to test the hypothesis, that pregnancy-related
diseases are going along with changes in cytokine mRNA-expression at the
placental site, either as a part of a pathological process or in connection with
regulatory mechanisms induced by disturbances at the feto-maternal interface
resulting from previous pathological changes--in the sense of counterregulation.
MATERIAL AND METHODS: The cytokines chosen for this investigation are known to
1.) be expressed in the human placental tissue, 2.) to be involved in
immunological processes and 3.) the regulation of growth and differentiation
processes of different cell types of the placenta or decidua, 4.) to play a role
in the angiogenesis at the feto-placental interface and 5.) to be involved in
pathological processes in other human diseases. 32 samples derived from term
human placentas were examined for messenger RNA levels of interleukin 1 alpha (II
1 alpha), tumor necrosis factor-alpha (TNF-alpha), platelet derived growth factor
A chain (PDGF-A), platelet derived growth factor-B chain (PDGF-B), and platelet
derived growth factor receptor (PDGF-R) using a semiquantitative reverse
transcriptase (RT) polymerase chain reaction (PCR) protocol. To calibrate samples
in our procedure, beta-actin mRNA (messenger ribonucleic acid) known as a "house
keeping" gene was proven to be constantly expressed. The sample-groups consisted
of normal pregnancies (n = 8), gestational hypertension (GH, n = 7), intrauterine
growth retardation (IUGR, n = 6), gestational diabetes mellitus (GDM, n = 5), and
gemini (n = 3 x 2). RESULTS: Throughout the 32 samples, a significant correlation
between PDGF-A and PDGF-R expression, PDGF-A and TNF-alpha expression was stated
(p = 0.007). Compared with the pattern of expression in normal placentas,
placentas of growth retarded pregnancies had higher Il-1 alpha mRNA (p = 0.016),
PDGF-A (p = 0.029) and PDGF-B (p = 0.001) levels. The samples of the gestational
hypertension group and placentas of patients with gestational diabetes displayed
a significantly stronger PDGF-R mRNA signal (p = 0.0029 and p = 0.008).
CONCLUSIONS: Though these marked differences in cytokine mRNA levels between
clinical groups were statistically proven, clear correlation of these differences
with clinical data was not found.
PMID- 11005133
TI - [Secondary malignant neoplasms in patients with breast cancer].
AB - OBJECTIVE: This report analyzes the occurrence of secondary malignancies among
patients with breast cancer. MATERIAL AND METHODS: We evaluated all women
diagnosed with breast cancer who were reported to the National Cancer Institute
of the former GDR in 1976. There was a follow up of 5,485 patients from 1976 to
1988 (38,231 person-years at risk). Cancer incidence rates of the whole female
population specific for age and calendar year were used for calculation of the
standardized incidence ratio (SIR). RESULTS: Significantly increased risks were
observed for neoplasms of the bilateral breast (SIR 2.44; 95% CI 2.04-2.93),
colon (SIR 1.53; 95% CI 1.06-2.12), rectum (SIR 1.65; 95% CI 1.10-2.40),
endometrium (SIR 1.55; 95% CI 1.02-2.27), and ovary (SIR 1.71; 95% CI 1.09-2.57).
Neoplasms of the lung (SIR 1.65; 95% CI 0.93-2.73), kidney (SIR 1.51; 95% CI 0.69
2.87), bladder (SIR 1.32; 95% CI 0.48-2.87), connective tissue (SIR 3.54; 95% CI
0.73-10.34), and multiple myeloma (SIR 1.98; 95% CI 0.54-5.06) were also
increased, not reaching statistical significance. Risk reduction was observed for
malignant tumors of the gallbladder (SIR 0.36; 95% CI 0.12-0.83). CONCLUSION: In
proposing recommendations for the follow-up and management of women with breast
cancer, it is important to recognize their long-term predisposition to an array
of secondary cancers.
PMID- 11005134
TI - [Efficiency of conventional glass wool and SpermFertil columns with respect to
ROS-reduction, leukocyte reduction, and CASA-generated sperm counts in semen].
AB - OBJECTIVE: Glass wool filtration has proved to be useful to separate motile from
defective spermatozoa and leukocytes in semen from patients with oligozoospermia
and azoospermia. With regard to that, we set out to investigate the efficiency of
two widely used filter systems. MATERIAL AND METHODS: Semen from 10 patients
attending the Dept. of Andrology, FSU Jena, were investigated with home-made
coarse glass wool filters and SpermFertil columns regarding elimination of
reactive oxygen species (ROS) and enrichment of semen with motile and progressive
spermatozoa. RESULTS: Filtration with home-made glass wool columns did not affect
the percentage of motile spermatozoa but increased that of progressive
spermatozoa. The whole cell count was decreased by a third. Leukocytes were
reduced by half and ROS by more than half. SpermFertil columns increased the
percentage of both motile and progressive spermatozoa and the whole cell count
was decreased severely. Leukocytes were eliminated almost completely, as were
ROS. CONCLUSIONS: Our results show the higher potential of SpermFertil columns to
enrich semen specimens with motile and progressive spermatozoa and to almost
completely eliminate leukocytes and ROS in comparison to home-made glass wool
columns. However, SpermFertil columns reduce the whole cell count to about 10% of
the original cell count.
PMID- 11005135
TI - [Desmoid tumor of the breast].
AB - The desmoid tumor of the breast with infiltrative and destructive growth
tendencies is a rare benign lesion. Fibromatosis management favors wide local
excision with clear margins, adjuvant hormonal- and radiotherapy can improve
recurrence-free survival rate. We report on a patient with desmoid tumor of the
breast.
PMID- 11005136
TI - [Atypical process of acute disturbance of liver function with severe
thrombocytopenia in the third trimester].
AB - The authors diagnosed disturbance of liver-function associated with severe
thrombopenia in a pregnant woman in the third trimester. Principally, acute fatty
liver of pregnancy can be characterized by existing symptoms, e.g. nausea,
vomiting, epigastric pain, jaundice, hyperbilirubinemia, moderately elevated SGOT
and SGPT levels, thrombopenia, leukocytosis, low fibrinogen level and
disseminated intravascular coagulopathy, but hepatomegaly, purpura and petechia
on lower and upper extremities, and high ALP and GGT levels during postpartum
period do not confirm suspicion of this diagnosis. The present report draws
attention to the difficulties of differential diagnosis of pregnancy-induced
elevated liver enzymes diseases associated with low platelets, as there are
several identical pathophysiological processes. Although causes and exact
pathophysiology of disorders are unknown, similar symptoms during the process of
diseases leave the question open whether they are different diseases or whether
they are different manifestations of the same disease, and what kind of
relationship exists between these diseases and preeclampsia. This case suggests
careful evaluation of the whole clinical picture, moreover it is emphasized that
prompt, aggressive treatment of hemostatic disturbance and the expeditious
delivery can save maternal life.
PMID- 11005137
TI - [Laparoscopic single patient use instruments: expensive outsourcing of product
quality?].
AB - The supply of medical goods is an important critical success factor in German
hospitals. One major managerial area in the procurement concerns the decision
between single patient use (SPU) and multiple patient use (MPU) products.
Especially laparoscopic instruments which are generally expensive are a field of
interest for decision makers. Due to a lack of quantifiable factors describing
the two different forms of supply alternatives with their effects on effectivity
and efficiency of the procurement process and the final use are often not taken
into account. Since it is expected that in the future more and more laparoscopic
instruments will be needed there is a necessity for finding a concept allowing
the identification of the "right" product. The Center for Hospital Management
(CKM) has the aim to develop a corresponding approach but needs the help of the
reader.
PMID- 11005138
TI - [Electronic documentation in medicine; flexible concepts versus isolated
solutions].
AB - Computer-based medical documentation so far proved advantageous especially
through standardization of data entry and increased access speed. Additional
benefits can be achieved through the implementation of integrated, cross-project
documentation tools and their integration into the clinical work-flow, which
allow data to be used for a wide variety of applications (e.g. quality
management, clinical research, clinic management). The presence of incompatible
documentation software often complicates the realization of these goals.
Implementation of new documentation tools therefore should consider flexibility
and multiple-use of data as primary design goals. In the presented paper
requirements for flexible documentation tools are introduced. The Entity
Attribute-Value-Model is described as a possible means of implementation.
Practical experiences made with a prototype application are reported.
PMID- 11005139
TI - [Interdisciplinary workshop "Hormone substitution and cardiovascular system".
Stuttgart, April 13-l4, 2000].
PMID- 11005140
TI - Hereditary colorectal cancer: risk assessment and management.
AB - There are at least nine major cancer susceptibility syndromes that infer an
increased risk for colorectal cancer and/or colorectal polyposis; hereditary
nonpolyposis colorectal cancer syndrome, Muir-Torre syndrome, Turcot syndrome,
the I1307K polymorphism of the APC gene, familial adenomatous polyposis,
attenuated familial adenomatous polyposis, Peutz Jeghers syndrome, juvenile
polyposis, and the PTEN hamartoma tumor syndrome. As a result, the differential
diagnosis of hereditary colorectal cancer can be complex. In addition, there has
been a dramatic increase in the knowledge available regarding risk assessment and
management of hereditary colorectal cancer syndromes. The literature was reviewed
to develop this concise review of the hereditary colorectal cancer syndromes to
facilitate the accurate diagnosis of each syndrome and the appropriate medical
care for individuals with these diagnoses. Referral to a qualified Clinical
Cancer Genetics program is appropriate if any of these syndromes is suspected and
they will ensure the most up-to-date information is available to the patient,
their family, and their health care professionals.
PMID- 11005141
TI - Low-density lipoprotein receptor gene mutations in a Southeast Asian population
with familial hypercholesterolemia.
AB - The aim of this study was to detect mutations in the genes coding for the low
density lipoprotein receptor and apolipoprotein B in patients of Southeast Asian
origin with clinically diagnosed familial hypercholesterolemia (FH) and to relate
these findings with the observed lower incidence of coronary heart disease in
this part of the world. A total of 86 unrelated patients with FH were selected on
clinical grounds, and complete DNA analysis of the low-density lipoprotein (LDL)
receptor and apolipoprotein B (apoB) genes by DGGE and DNA-sequencing was
performed. In the majority (73%) of the cohort studied, no mutations could be
detected, even after extensive analysis of the LDL-receptor and apoB genes.
However, the 22 patients with a mutation had significantly more xanthomas and a
higher incidence of coronary heart disease and levels of low-density lipoproteins
were also significantly different. There was no correlation between the type of
the mutation and lipoprotein levels or clinical signs of atherosclerosis. The
fact that the majority of the FH patients studied had no detectable mutation and
that this group had a significant milder phenotype, suggests the presence of a
third gene in the Southeast Asian population, predominantly leading to a disorder
resembling a milder form of FH. A similar, but less frequent, trait has recently
been described in a number of European families.
PMID- 11005142
TI - Trends in the frequencies of consanguineous marriages in the Israeli Arab
community.
AB - To assess the trends in the frequency of consanguineous marriages in the Israeli
Arab population in the last 40 years, we conducted a two-part study. For the
first part, we re-analyzed data from a nationwide study carried out in 1992, and
for the second part, we undertook a new survey in 1998 in four locations: Taibe,
Tira, Kalansuwa and Kafr Bara. Data regarding the frequency of consanguineous
marriage in these four locations for the years 1961-1985 was extracted from the
original survey, and for the years 1986-1998, from new questionnaires. The
frequency of consanguineous marriage was highest in the period 1961 1965 (50.6%),
but by the period 1981-1985 it had decreased to 40.6%. Over the whole time span
of the 1992 study, a significant decrease was observed between the periods 1961
1975 and 1976-1985 (p < 0.0001). In the four-location study, there was a
significant decrease in the frequency of consanguineous marriage from 52.9%, in
the period 1961-1970 to 32.8% in the period 1991-1998 (p = 0.0006). We conclude
that the custom of consanguineous marriage in the studied population is still
extremely high, and preventive measures should be taken to decrease its frequency
and associated complications.
PMID- 11005143
TI - Prenatal diagnosis of fragile X syndrome and the risk of expansion of a
premutation.
AB - The aim of the present study was to evaluate prospectively the dynamics of the
FMR1 gene. The risk of full mutation among pregnant women and the carriers, and
the risk of expansion of a premutation allele to a full mutation were estimated.
We identified 89 pregnant women with an expanded FMR1 gene seeking prenatal
diagnosis. Amniocentesis or chorion villus sampling (CVS) was offered and a DNA
test of the FMR1 gene was carried out in such pregnancies. The overall risk of
full mutation among women (N = 21) with a repeat size between 60 and 80 was 4.8%
(one fetus with mosaicism), and the risk of expansion of the premutation allele
to a full mutation was 14% in those offspring to whom the premutation allele was
transmitted. The risk of full mutation among the carriers (N = 13) with a repeat
size between 81 and 100 was 61.5% (8/13), and the risk of expansion of a
premutation allele to a full mutation was 89%. Only one case fell into the
category of 101-200 repeats, and expansion to a full mutation was recorded.
Fetuses of full mutation mothers inherited the larger allele in 64% (14/22) of
the cases. The range of 40-59 repeats was safe: there were no fetal full
mutations. The risk of full mutation was also low among the subjects with a
repeat size between 60 and 80, whereas the risk increased significantly after 80
repeats. Maternal premutation size was positively correlated with the risk of
having a full mutation offspring.
PMID- 11005144
TI - Molecular cytogenetic analysis of a duplication Xp in a female with an abnormal
phenotype and random X inactivation.
AB - We describe a female infant with severe abnormal phenotype with a de novo partial
duplication of the short arm of the X chromosome. Chromosome painting confirmed
the origin of this X duplication. Molecular cytogenetic analysis with
fluorescence in situ hybridization (FISH) was performed with YAC probes, further
delineating the breakpoints. The karyotype was 46, X dup(X)(p11-p21.2).
Cytogenetic replication studies showed that the normal and duplicated X
chromosomes were randomly inactivated in lymphocytes. In most females with
structurally abnormal X chromosomes, the abnormal chromosome is inactivated and
they are phenotypically apparently normal relatives of phenotypically abnormal
males having dupX. Therefore, in this case, there is functional disomy of Xp11
p21.2 in the cells with an active dup(X), most likely resulting in abnormal
clinical findings in the patient.
PMID- 11005145
TI - Prevalence of the C282Y mutation for haemochromatosis on the Island of Majorca.
AB - The C282Y mutation of the HFE gene has been reported to be present in most of the
patients with hereditary haemochromatosis (HH) of Northern European ancestry. HH
affects approximately 1/300 individuals, but it is not evenly distributed in the
different European countries. In the present study, polymerase chain reaction
(PCR) and restriction-enzyme digestion were used to analyse the frequency of the
most important mutation in haemochromatosis (C282Y) in subjects from Majorca
(Balearic Islands, Spain) and patients with haemochromatosis. The results were
compared with other studies from Spain and Europe. A total of 420 Majorcan
chromosomes were analysed and the C282Y mutation was observed at a frequency of
2.62%+/-0.8 (11 heterozygotes: eight men and three women). In the group of
hereditary haemochromatosis probands, 13 out of 14 were homozygous for the C282Y
mutation. In the distribution of the C282Y mutation, a north-west to south-east
cline was detected, supporting the Celtic origin of this mutation.
PMID- 11005146
TI - Telomere-telomere (end to end) fusion of chromosomes 7 and 22 with an
interstitial deletion of chromosome 7p11.2-->p15.1: phenotypic consequences and
possible mechanisms.
AB - We report a rare case of a de novo end to end fusion of chromosomes 7 and 22 in
conjunction with an interstitial deletion of chromosome 7p11.2p15.1 in a newborn
with congenital anomalies. The proband presented for chromosome analysis with
bilateral cataracts, dysmorphic facies and distal limb abnormalities. Chromosome
analysis showed a 45,XY,der(22)psu dic(22;7)(p13;p22.3)del(7)(p11.2p15.1)
karyotype. This short arm to short arm fusion of chromosomes 7 and 22 resulted in
a pseudodicentric chromosome. The interstitial deletion in the short arm of
chromosome 7 was likely a result of breakage and reunion related to instability
of the dicentric chromosome. Loss of genetic material in this region of
chromosome 7p has been implicated in the pathophysiology of craniosynostosis and
cephalopolysyndactyly syndromes.
PMID- 11005147
TI - Intrachromosomal triplications: molecular cytogenetic and clinical studies.
AB - A newborn boy had meconium aspiration syndrome, hypospadias, a supernumerary
digit on the left hand, hyperbilirubinemia, a fractured right clavicle,
osteopenia, liver calcification, and mild pulmonary hyperplasia. Cytogenetic
studies showed a chromosome 13 with additional material in 33% of the metaphases.
The add(13) was considered to be a probable duplication of 13q12q22. The 13 paint
probe hybridized to the add(13) from end to end. Fluorescence in situ
hybridization (FISH) studies using retinoblastoma probe (RB)-1 that maps to 13q14
and D13S585 that maps to 13q32-q33 gave one signal for RB and three signals for
D13S585. The pattern of the three signals from the 13q32q33 region and the G
banding pattern was best explained as a triplication of 13q22q33, with an
inverted middle repeat resulting in tetrasomy for this segment. Mosaicism was
confirmed by FISH using a D13S585 probe on a buccal smear. Three triplications
detected in our laboratory were compared 13q22q33, 15q11q13, and 2q11.2q21. FISH
was critical in identifying triplications 13q22q33 and 15q11q13. The
hybridization pattern also indicated an inverted middle repeat. We conclude that
intrachromosomal triplications may be more prevalent than previously assumed and
they probably share a common mechanism in their formation. When the G-bands do
not correspond exactly to a duplication or to a tandem triplication, an important
consideration is that the majority of triplications have an inverted middle
repeat. Triplications can be mistaken for duplications. Therefore, in assessing
duplications, FISH confirmation is recommended.
PMID- 11005148
TI - Chronic myelomonocytic leukaemia in a child with constitutional partial trisomy 8
mosaicism.
AB - We present a 3-year-old boy with constitutional partial trisomy 8 mosaicism
(karyotype 47,XY, + del(8)(p12)/46,XY) who developed chronic myelomonocytic
leukaemia and we review the few reported cases of constitutional trisomy 8
mosaicism (CT8M) associated with malignancy. This case highlights the association
between CT8M and the development of malignancies, haematological malignancies in
particular.
PMID- 11005149
TI - Mild clinical phenotype associated with R1158X/S549R(T-->G) CFTR genotype.
PMID- 11005150
TI - Genetic homogeneity of the Camurati-Engelmann disease.
PMID- 11005151
TI - Risk estimates for carriers of chromosome reciprocal translocation
t(4;9)(p15.2;p13).
PMID- 11005152
TI - A novel closed-tube quantitative--PCR method for enumerating Porphyromonas
gingivitis, Prevotella intermedia and Actinobacillus actinomycetemcomitans.
AB - Enumeration of specific periodontopathogens in subgingival plaque samples has
been problematic because of either lack of sensitivity, specificity or the time
taken to identify the organisms. These problems can be overcome using PCR, but
quantification by this technique is more difficult. We report a simple
quantitative PCR method developed for enumerating Porphyromonas gingivalis,
Prevotella intermedia and Actinobacillus actinomycetemcomitans in clinical
samples. The method relies upon inclusion of ethidium bromide in a closed-tube
PCR reaction and measurement of resultant amplicons by quantifying the
fluorescence generated when UV-light is passed through the walls of the
amplification tube. Hence, both PCR and detection are performed in the same tube.
The technique was compared with a quantitative competitive PCR and a commercial
colorimetric quantitative PCR and proved to be at least as sensitive, specific
and reliable for enumeration of the target bacteria. However, its speed and
convenience make it particularly useful for large-scale analyses in both clinical
laboratories and epidemiological studies.
PMID- 11005153
TI - Salivary matrix metalloproteinase (MMP-8) levels and gelatinase (MMP-9)
activities in patients with type 2 diabetes mellitus.
AB - We studied the salivary levels and activities of the matrix metalloproteinases
(MMP) -8 and -9 in 45 type 2 diabetic patients and 77 control subjects. The
patients' mean glycosylated haemoglobin (HbA1c) was 8.7%, indicating an
unsatisfactory metabolic control of the disease. The MMP levels were further
related to the clinical and microbiological periodontal findings as well as to
salivary flow rate and other factors. The salivary flow rate, albumin and amylase
concentrations were similar in type 2 diabetic patients to those in the control
group. The mean gingival and periodontal pocket indexes were higher in the
diabetes group. The number of potential periodontopathogenic bacteria was lower,
however, in the diabetic than in the control group. Zymography and immunoblotting
revealed that the major MMPs in the type 2 diabetic patients' saliva were MMP-8
and MMP-9. Salivary MMP levels and activities in type 2 diabetic patients were in
general similar to those in the control group. However, the correlation
coefficients using multiple regression analysis revealed that gingival bleeding,
pocket depths and HbA1c were associated with increased MMP-8 levels which, in
turn, were negatively predicted by elevated plasma lipid peroxide levels in the
diabetic group. Our data on salivary MMP-8 and -9 do not support the concept of
generalized neutrophil dysfunction in unbalanced diabetes. Moreover, plasma lipid
peroxidation levels reflecting the increased oxidative burden, which is generated
mainly by triggered neutrophils, do not indicate neutrophil dysfunction due to
diabetes, but may rather be related to the increased tissue damage in an
uncontrolled disease. However. advanced periodontitis in type 2 diabetes seems to
be related to elevated salivary MMP-8 levels which might be useful in monitoring
periodontal disease in diabetes.
PMID- 11005154
TI - In vitro evaluation of Er:YAG laser scaling of subgingival calculus in comparison
with ultrasonic scaling.
AB - The purpose of the present study was to evaluate the effectiveness of Er:YAG
laser scaling and the morphological and histological changes of the laser-scaled
root surface in comparison with the effectiveness and root surface changes
produced by conventional ultrasonic scaling. Fifty-three periodontally involved
human extracted teeth with a band of subgingival calculus were used. The teeth
were divided randomly into 2 groups for laser scaling and ultrasonic scaling.
Laser irradiation was performed at an energy output of 40 mJ/pulse and 10
pulses/s under water spray, with the probe tip contacted obliquely to the root
surface. Ultrasonic scaling was performed at a clinically standard power setting.
The time required for scaling, the scaled area and the temperature changes were
determined using both methods of treatment. The features of the scaled surfaces
were examined by histological and scanning electron microscope (s.e.m.)
observations. The Er:YAG laser provided subgingival calculus removal on a level
equivalent to that provided by the ultrasonic scaler, without major thermal
elevation. Macroscopically, the laser-treated root surface was somewhat rougher
than or similar to the ultrasonically scaled root. However, the efficiency of the
laser scaling was lower than that of the ultrasonic scaling. In addition,
histological examination revealed a thin deeply stained zone on the lased root
surface, and s.e.m. analysis revealed a characteristic microroughness on the
lased surface. The laser scaling provided a level of calculus removal that was
similar to that provided by the ultrasonic scaling. However, the Er:YAG laser
produced superficial, structural and thermal microchanges on the root cementum.
PMID- 11005155
TI - Herpesviruses 6, 7 and 8 in HIV- and non-HIV-associated periodontitis.
AB - Human herpesviruses, especially cytomegalovirus and Epstein Barr virus type-1,
occur with higher frequency in subgingival specimens from periodontitis lesions
than from healthy/gingivitis sites. Little or no information is available on the
relationship between herpesvirus 6 (HHV-6), herpesvirus 7 (HHV-7) and herpesvirus
8 (HHV-8) and periodontal disease. This study determined the periodontal
occurrence of HHV-6, HHV-7 and HHV-8 in 21 HIV-seropositive and 14 HIV-negative
adults affected by periodontitis. Gingival biopsy specimens and paper-point
samples of subgingival plaque were collected from sites showing 5 mm or more in
probing depth. Nested polymerase chain reaction methodology was employed in
herpesvirus identification. In the HIV-seropositive periodontitis group, 90% of
gingival biopsies and 62% of subgingival plaque samples revealed at least one of
the test viruses. HHV-6 occurred in 71%, HHV-7 in 67% and HHV-8 in 24% of
gingival biopsies. In the HIV-negative adult periodontitis group, 43% of gingival
biopsies showed at least 1 of the test viruses, with HHV-6 present in 21% and H
HV-7 in 29% of gingival biopsies and with no detection of HHV-8. The combined
occurrence of the 3 test herpesviruses was significantly higher in HIV
seropositive than in HIV-negative adult periodontitis patients (p = 0.008). The
human periodontium might constitute a site of infection or reservoir for HHV-6,
7, -8.
PMID- 11005156
TI - Glucocorticoid receptor antagonist RU 486 treatment reduces periodontitis in
Fischer 344 rats.
AB - Inappropriate hypothalamic pituitary adrenal (HPA) axis regulation of immune
responses to bacterial challenges has been found to play an important role in
infections and inflammatory disease susceptibility and progression. In the
present study we investigated the tissue effects of experimental periodontitis in
Fischer 344 rats, which were subcutaneously (s.c.) injected with 20 mg/kg of the
glucocorticoid receptor antagonist and active antiglucocorticoid agent RU 486
every second day over a period of 14 d. Periodontitis was induced by placing a
bacterial plaque retentive silk ligature in the gingival sulcus around the neck
of maxillary right 2nd molar teeth 1 d after the first injection in 10 RU 486
treated and 10 vehicle (1,2-propanediol)-treated control animals. The
contralateral maxillary left 2nd molars served as internal control teeth for
naturally occurring periodontitis. Disease progression was evaluated
radiographically and histometrically. The average level of corticosterone in
blood at sacrifice was significantly lower in the RU 486-treated animals as
compared to controls. The experimental animals also developed significantly less
periodontal breakdown at both experimental and control teeth compared to the
vehicle-treated control animals. The results support our recent findings showing
that HPA hyper-reactivity, either genetically determined or experimentally
induced, stimulates periodontal disease susceptibility. These findings suggest
that central nervous regulation of inflammatory responses to dental plaque
microorganisms in the gums may modulate periodontal disease susceptibility and
progression.
PMID- 11005157
TI - Cytostatic action of enamel matrix derivative (EMDOGAIN) on human oral squamous
cell carcinoma-derived SCC25 epithelial cells.
AB - During surgical treatment of periodontal disease, enamel matrix derivative (EMD)
is topically applied as a substitute for extracellular matrix in order to
facilitate regeneration of damaged periodontal tissue. However, the mechanism for
EMD action is poorly understood. We have now examined the effects of EMD on the
proliferation of oral epithelial (SCC25) cells in vitro. After 3 days of
treatments, EMD (25 100 microg/ml) dose-dependently inhibited cell division and
concomitantly arrested cell cycle at the G1 phase. Prior to this inhibition, EMD
significantly up-regulated p21WAF1/cip1, a cyclin-dependent kinase inhibitor,
induced G1-arrest, and inhibited DNA synthesis. In addition, EMD down-regulated
expression of cytokeratin-18 (CK18) protein, which was most due to decreased
production, but less to increased degradation. However, EMD did not discernibly
increase the number of apoptotic cells over 8 days of treatment. These findings
indicate (1) that EMD acts as a cytostatic agent, rather than a cytotoxic agent,
on epithelial cells, and (2) that this anti-proliferative action is probably due
to p21WAF1/cip1-mediated G1-arrest. Furthermore, our in vitro cellular data
clearly verify and provide an explanation for the clinical observation that EMD
application suppresses the down-growth of junctional epithelium onto dental root
surfaces, a process that frequently interferes with the formation of new
connective tissue attachments.
PMID- 11005158
TI - Altered expression level of calbindin D28k in the periodontal ligament of rat
molar in response to changes in occlusal force.
AB - The present immunohistochemical study was designed to investigate the alteration
in the expression level of calbindin D28k in the periodontal ligament of the rat
molar in response to changes in occlusal force to clarify the physiological
role(s) of this protein in the ligament. In normal periodontal ligament of the
lower first molar, immunoreactivity for calbindin D28k was found in the spindle
shaped cells, presumably fibroblasts, at the alveolar portion of the ligament at
the distal side of the mesial root and mesial side of the distal root. Following
the overload of occlusal force to the upper first molar by bite-raising, the
number and immunoreactivity of the positive cells in the periodontal ligament of
the lower first molar increased gradually. A more significant increase was
detected at 7 d following the bite-raising compared to the normal animals. When
occlusal force was removed by the extraction of the upper first molar, the
expression level of calbindin D28k in the periodontal ligament of the lower first
molar rapidly decreased, however a subsequent gradual increase was recognized.
Statistical analysis of the spatial immunoreactivity of calbindin D28k in the
periodontal ligament was performed and showed statistically significant
differences. The present results suggest that calbindin D28k may play important
roles in the homeostasis and cytoprotection of the periodontal fibroblasts
against occlusal force.
PMID- 11005160
TI - Floating the data acquisition chains to improve the quality of measurements.
AB - Guarding sensors and measuring equipment is a smart operation which decouples the
apparatus or systems from common mode electrical disturbances. In this context,
the floating techniques are revisited and the usual measurement problem in noisy
environment is outlined. It is shown that the use of differential inputs to
pickup sensor continuous signals, as well as simple shielding and grounding
techniques lead to increase the quality of data acquisition systems. At the other
size, optical couplers allow to pass the digital version of data to an external
bus or to a network by preserving the apparatus floating features.
PMID- 11005159
TI - Improvement of macromolecular clearance via lymph flow in hamster gingiva by
topical warming and massage.
AB - The lymphatic system is very important for macromolecular clearance in various
tissues, especially in the gingiva. However, the kinetics of macromolecular
clearance via the lymph flow in the gingiva are poorly understood. The aim of
this study was to investigate whether thermal or mechanical stimulation affects
macromolecular clearance via the lymph flow in the gingiva. Carbon black
suspension was injected into the mandibular gingiva of anesthetized hamsters and
its drainage into cervical lymph nodes was examined. Clearance of 14C-methylated
bovine albumin and tritiated water from the gingiva and their drainage into
submandibular lymph nodes and blood was quantified. The effect of topical warming
or massage on clearance of 14C-methylated albumin from the gingiva during a 15
min period was examined. In addition, the influence of neurochemical antagonists
on the stimulatory effect of topical warming on albumin clearance was
investigated. Submandibular lymph nodes were clearly delineated by carbon black
10 min after the injection. More radiolabeled albumin appeared in submandibular
lymph nodes than in serum, while more tritiated water appeared in serum. Topical
warming (45 degrees C, 2 min) and warming plus massage (with a silicon rubber
brush, 20 s) decreased the radiolabeled albumin in the gingiva 15 min after the
injection. There was less radiolabeled albumin in the gingiva after gingival
warming plus massage than after warming. Previous injection of HOE140 or
propranolol into the gingiva diminished the stimulatory effect of topical warming
on albumin clearance. It was concluded that topical warming plus massage improves
macromolecular clearance via the lymph flow in hamster gingiva.
PMID- 11005161
TI - Pattern classification by a neurofuzzy network: application to vibration
monitoring.
AB - An innovative neurofuzzy network is proposed herein for pattern classification
applications, specifically for vibration monitoring. A fuzzy set interpretation
is incorporated into the network design to handle imprecise information. A neural
network architecture is used to automatically deduce fuzzy if-then rules based on
a hybrid supervised learning scheme. The neurofuzzy classifier proposed is
equipped with a one-pass, on-line, and incremental learning algorithm. This
network can be considered a self-organized classifier with the ability to
adaptively learn new information without forgetting old knowledge. The
classification performance of the proposed neurofuzzy network is validated on the
Fisher's Iris data, which is a well-known benchmark data set. For the
generalization capability, the neurofuzzy network can achieve 97.33% correct
classification. In addition, to demonstrate the efficiency and effectiveness of
the proposed neurofuzzy paradigm, numerical simulations have been performed using
the Westland data set. The Westland data set consists of vibration data collected
from a US Navy CH-46E helicopter test stand. Using a simple fast Fourier
transform technique for feature extraction, the proposed neurofuzzy network has
shown promising results. Using various torque levels for training and testing,
the network achieved 100% correct classification.
PMID- 11005162
TI - The development of reactor coolant pump vibration monitoring and a diagnostic
system in the nuclear power plant.
AB - Monitoring abnormalities within reactor coolant pumps due to vibration, we
introduce a Wigner distribution (WD) to a vibration monitoring system for
analyzing vibration signals, and develop an on-line diagnostic method using the
neural network employing back propagation algorithm. A rotor kit is used to
simulate the abnormal conditions in the pump such as bearing rubbing, shaft
bending, misalignment, etc. The data collected from the kit are analyzed using
both a conventional system based on the Fourier transform (FT) and the software
developed with the WD in this study, and they are compared. The study shows that
spectrum represented by WD makes it easy to analyze the vibration signals of a
rotating machine and the developed diagnostic method will help the operators
grasp the cause of vibrations.
PMID- 11005163
TI - PID gain scheduling using fuzzy logic.
AB - A simple, yet robust and stable alternative to proportional, integral, derivative
(PID) gain scheduling is developed using fuzzy logic. This fuzzy gain scheduling
allows simple online duplication of PID control and the online improvement of PID
control performance. The method is demonstrated with a physical model where PID
control performance is improved to levels comparable to model predictive control.
The fuzzy formulation is uniquely characterized by; (i) one fuzzy input variable
involving the PID manipulated variable, (ii) two parameters to be tuned, while
previously tuned PID parameters are retained, and (iii) a gain scheduling
differential equation which relates the fuzzy and conventional PID manipulated
variables and enables fuzzy gain scheduling.
PMID- 11005164
TI - Intelligent control of a cryogenic cooling plant based on blackboard system
architecture.
AB - Intelligent system techniques have been rapidly assimilating into process control
engineering, with many applications reported in the last decade. Intelligent
control is bringing a new perspective as well as new challenges to process
control. In this paper, a software architecture for a Blackboard for Integrated
Intelligent Control Systems (BIICS) is described. The system is designed to
simultaneously support multiple heterogeneous intelligent methodologies, such as
neural networks. expert systems, fuzzy logic, neural networks and genetic
algorithms. It will be shown how such methodologies can be readily assimilated
into the software architecture. The BIICS system represents a multi-purpose
platform for design and simulation of intelligent control paradigms for different
kinds of processes. Currently the system utilizes intelligent control techniques
(neuro-fuzzy and genetic optimization) for controlling a cryogenic plant used for
superconductor testing at temperatures below 100 K.
PMID- 11005165
TI - Soft-testing of industrial control systems programmed in IEC 1131-3 languages.
AB - This paper presents a technique and the means for testing PLC-based control
software outside the actual plant environment with the purpose of increasing the
confidence level on the compliance of the software to functional and temporal
requirements. The need to obtain a high confidence level on the correct software
operation arises from the fact that in most of the cases it is quite dangerous
and expensive to test unproved PLC operation by linking it with the actual
facilities that it is going to control. The proposed technique relies on a
combined simulation of the controlled plant and the PLC system and an analysis of
the plant responses. The PLC system simulation imitates the way software is
executed on a PLC that is programmed in the languages of the IEC1131-3 standard.
It is based on the programming model of the IEC standard and analytical formulae
for estimating the program runtime. The simulation of the plant is based on a
discrete convolution model that is solved at the same rate with the rate
determined by the control algorithms. A tool realizing these concepts has been
developed and its use in testing the control software of three critical outputs
of a distillation column is demonstrated.
PMID- 11005166
TI - Expanding the applicability of ISA TR84.02 in the field.
AB - The ANSI/ISA S84.01 standard was released in 1996. The companion technical report
TR84.02 is in the process of being completed. The latter document is intended to
provide the methodology to implement the safety performance requirements of the
standard for the safety system. In this document, three techniques are presented;
these being Simplified Equations, Fault Tree Analysis and Markov Modeling. Of the
three, only the Simplified Equations approach would reasonably be utilized in the
field by plant personnel. The Simplified Equations provided as part of TR84.02
comprehend common cause failures, systematic failures, and second failure prior
to repair scenarios. They do not however comprehend the use of redundant field
devices which are dissimilar, and as such have different failure rates. This
situation is quite common in practice, and simple to manage using enhanced
equations for the computation of PFDavg. A set of these equations for typical
redundant architectures in the field, and several examples of their applications
in safety loop analysis are derived and presented in this paper.
PMID- 11005167
TI - A method to prevent excessive numbers of Markov states in Markov models for
quantitative safety and reliability assessment.
AB - This paper presents a method that will drastically reduce the calculation effort
required to obtain quantitative safety and reliability assessments to determine
safety integrity levels for applications in the process industry. The method
described combines all benefits of Markov modeling with the practical benefits of
reliability block diagrams.
PMID- 11005168
TI - Consecutive matching striation criteria: a general critique
AB - In the forensic science of firearms and toolmark identification, examiners
traditionally have drawn conclusions of identity from subjective criteria. This
paper critically explores the general validity of one proposed objective-criteria
regime--that of counting consecutive matching striations on fired bullets.
Practical considerations are discussed, as well as theoretical ones, with both
discussions viewed from the perspective of Bayesian logic. It is concluded that
drawbacks exist for this particular objective-criteria regime, but that research
and logical analysis should continue.
PMID- 11005169
TI - Identification of heroin in street doses using 1D-TOCSY nuclear magnetic
resonance
AB - Heroin street doses are complex mixtures commonly analyzed in forensic
laboratories. Identification of the illicit substance in these street doses is
among the primary analytical tasks of a forensic laboratory. We demonstrate that
the one-dimensional ID-TOCSY NMR experiment permits identification of heroin in
standard mixtures containing up to ten or more different components. This method
produces an easily-identified and effective "fingerprint" for heroin within a
mixture of other substances. The method has been successfully tested as a tool
for identification of heroin in street doses from police casework in Israel. This
NMR technique is robust and quick (a measurement can be carried out in 10-15
min), and it does not require any preliminary physical or chemical treatments of
the sample to be examined, due to the effective spectroscopic "filtering" of the
interfering components. The ID-TOCSY NMR method can potentially be used in
combination with additional analytical methods as a routine tool in forensic
laboratories to positively identify heroin for court purposes.
PMID- 11005170
TI - The petroleum-laced background
AB - Using passive headspace concentration (ASTM E-1412) and gas chromatographic/mass
spectrometric (GC/MS) analysis as described in ASTM E-1618, the authors have
studied the volatile components detectable in several kinds of otherwise
uncontaminated substrata, including clothing, shoes, household products, building
materials, paper products, cardboard, and adhesives. Due to the use of petroleum
derived liquids in the manufacture of these materials, it is frequently possible
to detect the liquids, even when the products are several years old. These
results point out the need for the use of comparison samples whenever possible.
PMID- 11005171
TI - A novel method for forensic DNA investigations: repeat-type sequence analysis of
tandemly repeated mtDNA in domestic dogs.
AB - A highly variable and heteroplasmic tandem repeat region situated in the
mitochondrial mt DNA control region (CR) in domestic dogs and wolves was studied
to evaluate its suitability as a forensic genetic marker for analysis of single
hairs. The tandem repeat array is composed of three 10-bp repeat types that are
distributed so that a secondary DNA sequence is formed. Thus, the region presents
two levels of variation: variation in the number of repeats and variation in the
secondary DNA sequence of repeat types. Two analysis methods were therefore
tested; fragment length analysis and analysis of the sequence of repeat types.
Fragment analysis produced unique profiles that could be used to discriminate
between blood samples from maternally closely related individuals. However,
different hairs from one individual did not have the same fragment profile, and
the method is, therefore, not suitable for analysis of single hairs. In contrast,
analysis of the repeat type sequences (array types) is highly informative. When
different hairs from one individual were studied, identical array types were
found. The repeat-type sequence variation was studied among individuals having
identical nonrepetitive CR mtDNA sequence variants. Seven, six, and two
individuals, representing three different sequence variants, respectively, were
analyzed. All these individuals had different array types, which implies a very
high genetic variation between individuals in this region. The analysis method
considerably improves the exclusion capacity of mtDNA analysis of domestic dogs
compared with sequence analysis of non-repetitive DNA.
PMID- 11005172
TI - Improved method for shooting distance determination. Part 2--bullet holes in
objects that cannot be processed in the laboratory
AB - An improved method for firing distance determination on exhibits that cannot be
processed in the laboratory such as cars, doors, windows, or furniture is
described. The novel part of the method includes transfer of total nitrite
(nitrite ions and smokeless powder residues) from the target to an adhesive
lifter. After the transfer, vaporous lead and copper deposits around the bullet
entrance hole are visualized on the target by sodium rhodizonate and rubeanic
acid, respectively. The Modified Griess Test is carried out after alkaline
hydrolysis of the smokeless powder residues on the adhesive lifter.
PMID- 11005173
TI - Analysis of genotype frequencies and interlocus association for the PM, DQA1, and
D1S80 loci in four populations.
AB - Allele frequencies of the LDLR, HBGG, GYPA, D7S8, GC, DQA1, and D1S80 loci are
presented and genotypes are analyzed for each of four ethnic groups: African
Americans (n = 200), US Caucasians (n = 200), US Hispanics (n = 200), and
Japanese (n = 89). Hardy-Weinberg genotypic proportions were observed in all but
two of the 28 population-locus tests undertaken. Those two instances are
attributable to type I statistical error. Gametic equilibrium among loci is an
assumption invoked for application of the product rule to utilize the
discriminatory power from two or more loci simultaneously. Two statistical
methods, a genotype matching statistic and log-linear modeling, were used to
evaluate gametic disequilibrium. The match statistic, comparing observed to
expected likelihood of genotypic identity for seven loci among pairs of
individuals within the database, revealed only one statistically significant
deviation among 20 tests. As expected, the probability of match was generally
lowest in the test on all ethnic groups combined, indicating that allele
frequencies differ among ethnic groups for some of the loci. This was confirmed
with the statistic theta to measure ethnic stratification, in which about 0.10 of
the genetic variation is apportioned among the four ethnic groups for four of the
structural loci (LDLR, HBGG, GC, and DQA1), while for GYPA, D7S8, and D1S80,
variation is more uniformly distributed among ethnic groups. Log-linear modeling
was also applied to the five PM loci. The most parsimonious log-linear model
included only three higher order terms: the two-way interactions of three of the
PM loci with ethnic group. These three instances (LDLR, HBGG, and GC) indicated
differences in allele frequencies between ethnic groups. No two or higher way
interaction (disequilibrium) was observed among loci. In summary, the assumptions
of Hardy-Weinberg and gametic equilibrium that facilitate the use of the five PM
loci, DQA1 and D1S80 in forensic applications are consistent with the allele and
genotype frequencies observed in these populations.
PMID- 11005174
TI - A rare mutation in the amelogenin gene and its potential investigative
ramifications.
AB - Over the past few years, the Australian forensic science community has adopted a
common methodology and technology in the application of DNA profiling for
investigative and forensic purposes. The ultimate objective of this initiative is
the establishment of a national DNA database similar to that used in the UK. An
integral part of this methodology is the use of "Profiler Plus," a nonaplex of
STRs combined with amelogenin, a locus utilized for sex determination. This paper
reports the results from a case where a mutation in the annealing region of the
amelogenin primers appears to have resulted in the failure to amplify the
amelogenin Y-homolog from a phenotypically normal male. The result was confirmed
using two different primer sets that amplify different regions of the amelogenin
gene. This situation suggests that the genetic determination of sex based on the
amelogenin sequences from specimens of unknown origin, such as crime scene
samples, should not be considered infallible.
PMID- 11005175
TI - Hate crimes on the internet.
AB - The Internet serves as a channel for electronic communication on an international
level. While communication on the Internet has grown exponentially, the
proliferation of crimes in cyberspace has become rampant. Hate crimes, in
particular, have become increasingly prevalent on the Internet. In this past
decade, the United States government has taken significant measures to combat the
proliferation of hate crimes. This paper reports six cases of "cyberhate" crimes
and emphasizes pertinent legal issues surrounding them. Current modes of
intervention are discussed, ranging from local to national levels. The forensic
psychiatrist may undertake a challenging role in the interpretation of the
hateful criminal mind at the interface of psychiatry and the law.
PMID- 11005176
TI - Scanning electron microscopic analysis of skin resolution as an aid in
identifying trauma in forensic investigations.
AB - The forensic investigator is frequently confronted with cases that present with
wounds and blunt force trauma. Presently, the forensic investigator depends upon
previous experience and further investigative deduction of the crime scene to
analyze these injuries. Although not readily apparent to the naked eye, many skin
tissue injuries can be visualized with scanning electron microscopy (SEM). This
study was designed to establish skin trauma resolution using SEM in various skin
preparations. Tissue trauma was induced on leather, preserved skin, fresh skin,
and living skin using dies of varying thread size. Calibrated pressure forces in
pounds per square inch (psi) were applied and impressions made using vinyl
polysiloxane. Positive replicas of the tissues were prepared for SEM using
isocyanate resin. After sputter coating the cast with 35 nm of gold-palladium,
electron micrographs were generated using a Jeol JSM-5310LV scanning electron
microscope. To establish resolution, thread widths of 52, 104, and 208 threads
per inch (tpi) and trauma forces of 150, 200, and 250 psi were used to produce
the impressions. Microgrooves that were identified on the die threads were
analyzed. The optimum pressure for resolution studies was 150 psi using the 52
tpi die on the leather sample (4.67 +/- 0.88 microm, p = 0.046 and 0.025,
respectively, by ANOVA). The resolution was compared to that of leather using
preserved, fresh, and living skin. The resolution in preserved and fresh skin was
less than for leather (9.00 +/- 1.73 and 10.5 +/- 4.5 versus 4.67 +/- 0.88
microm, p = 0.09 and p = 0.20, respectively). Living skin resolution was 3 microm
at 52 tpi and 100 psi. Various implements of blunt force trauma were also
examined using the leather sample. Time after trauma resolution was examined at 0
(3 microm), 5 (6 microm), 10 (8 microm), and 20 (9 microm) min in living tissue.
A comparison between the microgrooves on the die replicas and the tissue trauma
impressions revealed striking agreement for both linearity and resolution.
Analysis of the microgrooves suggests that discrete morphological characteristics
are seen in skin tissue traumas. This method could expand the tools available for
the forensic investigation of blunt force trauma.
PMID- 11005177
TI - Time trends in a study of 440 mass slayings/rampages occurring in public places.
AB - We looked for variations in the timing of mass slayings/rampages (MS/R) committed
in public places by solitary perpetrators. News reports on 440 MS/R from 1920 to
1996 yielded 379 onset times which were examined for temporal patterns. There was
a dramatic increase in the number of MS/R from 1966 to 1995. We observed a
significant monthly variation with peaks in July-August and December, and a
bimodal daily rhythm for MS/R onset with a major peak at 11:00 a.m. and a minor
peak at 8:00 p.m. Observed time trends for MS/R could help develop protective
programs to reduce stress and violence in public places.
PMID- 11005178
TI - Elimination of 7-aminoflunitrazepam and flunitrazepam in urine after a single
dose of Rohypnol.
AB - The hypnotic benzodiazepine flunitrazepam (Rohypnol) has been identified as the
drug of choice for the purposes of "drugging" unsuspecting victims and raping
them while they are under the influence of this substance. The objective of this
paper was to study elimination of flunitrazepam and 7-aminoflunitrazepam in urine
collected from ten healthy volunteers who received a single 2 mg oral dose of
Rohypnol, to determine how long after drug administration 7-aminoflunitrazepam
can be detected. A highly sensitive NCI-GC-MS method for the simultaneous
quantitation of flunitrazepam (LOQ 100 pg/mL) and 7-aminoflunitrazepam (LOQ 10
pg/mL) in urine was developed. All samples were screened for benzodiazepines
using optimized micro-plate enzyme immunoassay. The highest concentrations of 7
aminoflunitrazepam (70-518 ng/mL) and flunitrazepam (0.7-2.8 ng/mL) in urine were
observed 6 h after drug administration in nine subjects and after 24 h in one
subject. In six subjects 7-aminoflunitrazepam was detected up to 14 days after
flunitrazepam administration, in one subject up to 21 days and in three subjects
up to 28 days. In urine samples collected from six volunteers, flunitrazepam was
detected three days after Rohypnol intake, in three subjects 24 h, and in one
subject 5 days later. Benzodiazepine micro-plate enzyme immunoassay kit allowed
the detection of flunitrazepam and metabolities 5 to 21 days after drug
administration.
PMID- 11005179
TI - Regional distribution of cocaine in postmortem brain of chronic human cocaine
users.
AB - We measured concentrations of cocaine and its major metabolites (benzoylecgonine,
ecgonine methylester, norcocaine, and cocaethylene) in 15 autopsied brain regions
of 14 human chronic cocaine users. Only slight differences were observed in
concentrations of cocaine and its metabolites amongst the examined brain areas.
Although it is likely that some postmortem redistribution of the drug must have
occurred, our data are consistent with the possibility that behaviorally relevant
doses of cocaine are widely distributed throughout the brain of humans who use
the drug on a chronic basis. Consideration should therefore be given to the
possible pharmacological and toxicological actions of cocaine in both striatal
and extra-striatal brain areas in human users of the drug.
PMID- 11005181
TI - A study on the use of photopolymer reflex plate in the forgery of Chinese seals
AB - This study compares the identifying characteristics between the impressions made
with original Chinese seals and photopolymer replicate seals, and between the
impressions made with two photopolymer replicate seals that originate from one
single negative. Various seal materials common to the Chinese community such as
cow's horns and ivory are employed. Other than the common factors such as
different incident angle upon imprinting or different degree of inking that
constitute the natural variation in impressions, the physical changes of the seal
materials with temperature will be considered. This study concludes that
photopolymer replicate seal impressions can be differentiated from the originals
in respect to print density and stroke morphology, but it is very difficult to
differentiate between two photopolymer replicate seal impressions with the same
origin. This study also proposes a simple method for the examination of forged
Chinese seal impressions.
PMID- 11005180
TI - Strontium isotope composition of skeletal material can determine the birth place
and geographic mobility of humans and animals.
AB - The Sr isotope composition measured in skeletal elements (e.g., bone, teeth, or
antlers) can be used to infer the geographic region that an animal or human
inhabited, because different regions tend to have distinct Sr isotope
compositions, and natural variations in the relative abundance of Sr isotopes are
not changed as Sr is processed through the food chain. Therefore, an organism
that ingests Sr from one region can have a Sr isotope composition that is
different than that of an organism that ingests Sr from another region. The Sr
isotope composition of skeletal elements is a reflection of the concentration
weighted average of dietary Sr that was ingested while that skeletal element was
produced. Because different skeletal elements grow and exchange Sr at different
stages during the life times of organisms, Sr isotope analysis of different
skeletal elements can be used to infer changes in geographic location at
different stages in an organism's life. The Sr isotope composition measured in
human teeth will reflect the average Sr isotope composition that was ingested as
a child, due to the immobile nature of Sr and Ca in teeth after formation,
whereas the Sr isotope composition of bone will reflect the average isotopic
composition over the last ten years of life, due to continuous biological
processing of Sr and Ca in bone. Inferring the average isotopic composition of
dietary Sr is best done by analyzing skeletal fragments from control groups,
which might be animals that have the same feeding habits as the animal in
question, or, in the case of humans, analysis of close family relatives. In cases
where it is not possible to construct a Sr isotope database from control groups,
it becomes necessary to estimate the isotopic composition of dietary Sr based on
geologic principles. We present three case studies from our research that
illustrate a range of approaches: (1) results from a criminal case where a deer
was illegally harvested and the location of the deer was important to establish,
(2) a pilot study of commingled human remains from a burial in Vietnam,
associated with the Vietnam Conflict, and (3) a study of 13th and 14th century
migration of peo ple from an archeological site in the Southwest United States.
PMID- 11005182
TI - Age estimation from sternal ends of ribs by phase analysis in South African
Blacks.
AB - The sternal ends of ribs are used in age determination of unknown adult remains.
Standards for American populations have been described and tested. The method
described by Iscan et al. is reviewed and compared with other age markers of the
human skeleton. Three hundred and thirty-nine (265 male, 74 female) sternal ends
of right fourth ribs, belonging to black individuals deceased in the Gauteng
Province of South Africa, were collected during 1994, 1995, and 1996. Three South
African investigators applied the existing method and found the repeatability
among them acceptable, although the method was less accurate to predict age in
this population. New phases with adjusted criteria and age ranges were developed
specifically for the South African black population. A tendency toward delayed
maturation was found, as well as a diversion of the appearance of female ribs
perimenopausally. Future studies involving more individuals in the older age
ranges, and females of all ages, could broaden the representativeness of these
phases.
PMID- 11005183
TI - Allele and genotype frequencies for D1S80 and 3'APOB in Recanati, Central Italy.
AB - The VNTR 3'APOB and D1S80 loci were studied in a sample of 179 individuals living
in the Recanati Area (Central Italy). For 3'APOB, we found 34 genotypes and 11
alleles. The system was in Hardy-Weinberg equilibrium. The observed and expected
heterozygosity were 0.788 and 0.798 respectively. The discrimination power was
0.96, the a-priori paternity exclusion power was 0.619 and the polymorphism
information content was 0.773. For D1S80, we found 45 genotypes and 18 alleles.
The system deviated significantly from Hardy-Weinberg equilibrium. The observed
and expected heterozygosity were 0.696 and 0.790 respectively. The discrimination
power was 0.96, the a-priori paternity exclusion power was 0.617 and PIC was
0.767. The Recanati sample was compared with the general Italian frequencies for
the 3'APOB locus. A difference of borderline significance was detected (P =
0.04). For D1S80, the sample was compared with a sample from Southern Italy and
no significant difference was detected.
PMID- 11005184
TI - Population frequency distribution of HumF13A01, HumFXIIIB, and HumLIPOL loci in
the Basque Country (Northern Spain).
AB - A population study of unrelated individuals from the Basque Country (Northern
Spain) was carried out using the GenePrint STR System. The PCR products were
separated on denaturing polyacrylamide gels and visualized by silver staining.
Three tetrameric loci were evaluated: HumF13A01, HumFXIIIB, and HumLIPOL. All
loci fit Hardy-Weinberg expectations, and independence of alleles was found
between these STR loci. A comparison with other population groups indicated
allele frequencies are well conserved in Caucasians, but differ from other racial
groups. The calculated parameters a priori probability of exclusion (Pex) and
"power of discrimination" (PD) show how informative these loci are for the
determination of identity and relatedness of individuals.
PMID- 11005185
TI - Loss of heterozygosity detected in a short tandem repeat (STR) locus commonly
used for human DNA identification.
AB - Short tandem repeat (STR) markers are commonly used in basic genetic research and
in human identification testing. Clinically, STRs can be used to study genetic
alterations in tumors. A genetic deletion common to many types of cancer is
referred to as the loss of heterozygosity (LOH). Numerous examples of LOH in
cancer have been described and some have been mapped to areas located in close
proximity to markers employed in human identity testing. Despite this fact, LOH
has rarely been observed for STR loci commonly employed in forensic testing.
Recently, for medico-legal purposes, we were asked to determine whether a tissue
biopsy originated from a particular individual. For a reference source we
assessed two specimens, one from normal tissue and one from cancerous tissue.
When both reference specimens were used to generate DNA profiles, we observed LOH
at one STR locus, D13S317. As demonstrated in other cancers only the cancerous
biopsy demonstrated LOH. The forensic community should be cognizant of these
unusual circumstances because, as identification of human DNA continues to be
used more extensively, certain instances will arise in which reference material
will not be readily available. In these situations, archived specimens may be
employed as a reference source. Clinical specimens such as tissue biopsies should
be used with caution if they have not been confirmed to contain normal tissue.
PMID- 11005186
TI - The presumptive reagent fluorescein for detection of dilute bloodstains and
subsequent STR typing of recovered DNA.
AB - A presumptive reagent for dilute blood detection other than luminol is
fluorescein. The sensitivity of fluorescein approaches the sensitivity of
detection levels of luminol. The fluorescein detection method offers the
advantages of working in a lighted environment, and the reaction persists longer
than luminol. A series of diluted bloodstains, ranging from neat to 1:1,000,000,
was placed on a variety of substrates. Three sets were made per substrate. One
set was exposed to fluorescein, one set was exposed to luminol, and one set
served as an uncontaminated control. The fluorescein signal persisted longer than
luminol. However, background staining for fluorescein was observed on some
substrates within 30 s to 1 min, and no background staining was observed for
luminol. Stains on non-absorbent surfaces were detectable at 1:100,000 dilutions,
and stains on absorbent surfaces were detectable usually at no more than 1:100.
The sensitivity of detection of fluorescein was comparable to that of luminol in
this study. In all cases, where sufficient DNA was recovered, typeable results at
all 13 core CODIS STR loci were obtained from treated bloodstains and controls.
The results from STR typing indicate that there was no evidence of DNA
degradation.
PMID- 11005187
TI - RFLP band size standards: NIST standard reference material 2390.
AB - The procedural standard for DNA profiling developed by the U.S. advisory board on
DNA quality assurance methods mandates annual confirmation of forensic DNA
measurement systems against an appropriate reference material supplied by or
traceable to the National Institute of Standards and Technology (NIST). NIST
Standard Reference Material (SRM) 2390 is a suitable and appropriate standard for
HaeIII restriction enzyme-based restriction fragment length polymorphism (RFLP)
profiling systems. Originally issued in 1992, an among-laboratory SRM 2390
recertification study was initiated in 1997. Using data provided by the 20 state,
local, or commercial forensic laboratory participants, quantitative band sizes
values (expected mean values and associated bivariate tolerance intervals) are
established for two different-source DNAs (female cell line K562 and healthy male
"TAW") for genetic loci D1S7, D2S44, D4S139, D5S110, D1OS28, and D17S79. Methods
for validating an RFLP measurement system, validating a control material or other
secondary standard, and for tracing a particular set of RFLP measurements to NIST
SRM 2390 are described in detail.
PMID- 11005188
TI - RFLP band size standards: cell line K562 values from 1991 to 1997 proficiency
studies.
AB - Cell line K562 is the defacto forensic control material for forensic restriction
fragment length polymorphism (RFLP) DNA profiling in the U.S. Fifty-one
proficiency tests conducted from 1991 through 1997 enable a detailed description
of RFLP measurement performance during this period. Sufficient data are available
to define reference distributions for all commonly utilized and many less
commonly reported genetic loci, for both HaeIII- and HinfI-based RFLP systems.
The average measured size of HaeIII locus D1S7 and D5S110 bands has varied
slightly over time; while relatively small, these temporal changes add to the
overall interlaboratory measurement uncertainty. The characteristic standard
deviation for HinfI RFLP system measurements has a nearly identical dependence on
expected band size as does the standard deviation for HaeIII measurements. The
ellipsoidal distance, K, is suggested for use as an RFLP data quality metric; the
critical threshold value that on average excludes 1% of plausibly valid
proficiency data for a given polymorphic locus is K1% = 14.2.
PMID- 11005189
TI - The identification of 2-chloro-4,5-methylenedioxymethylamphetamine in an illicit
drug seizure
AB - This work outlines the unequivocal identification of the "ecstasy" analog, 2
chloro-4,5-methylenedioxymethylamphetamine, using combined gas
chromatography/mass spectroscopy (GC/MS) and proton magnetic resonance
spectroscopy (1H-NMR). This compound was identified along with 3,4
methylenedioxymethylamphetamine (MDMA) in an illicit tablet seizure, which
included 26 off-white tablets.
PMID- 11005190
TI - The effects of microwave irradiation on occluded solvents in illicitly produced
cocaine hydrochloride
AB - The current clandestine methodology for the manufacture of illicit cocaine
hydrochloride utilizes microwave heating in order to dry the finished product.
This study addresses the effects this step has on the occluded solvents present
in newly prepared cocaine hydrochloride. Nine 1-kilogram-sized batches of cocaine
hydrochloride were prepared from cocaine base using a variety of solvents or
solvent mixtures commonly utilized in clandestine laboratories, pressed into
bricks, and submitted to microwave heating. Residual solvents were qualitatively
and quantitatively monitored before, during, and following the microwaving step
by static headspace-gas chromatography-mass spectrometry. All solvents used in
the conversion process were easily detected in the bricks even after extensive
irradiation, confirming that occluded solvents are extremely resistant to removal
by microwave heating. Qualitative and quantitative data corresponding to the
residual solvents in the prepared cocaine hydrochloride bricks are presented.
PMID- 11005191
TI - Analysis of biofluids for flunitrazepam and metabolites by electrospray liquid
chromatography/mass spectrometry.
AB - A rapid and sensitive liquid chromatography/electrospray ionization mass
spectrometry (LC/MS) procedure has been developed for the analysis of biofluids
containing flunitrazepam and its metabolites. Specimens were spiked with
deuterated analogs of the analytes. Urine specimens were enzymatically hydrolyzed
and blood specimens were untreated. Extractions were carried out using
CleanScreen DAU SPE cartridges. The drugs were separated on a C18 column using a
methanol-water-ammonium hydroxide (60:40: 0.03 v/v) mobile phase. After
determination of base peaks using full scan mass spectrometry, the mass
spectrometry method was optimized to operate in selected-ion monitoring (SIM)
mode for the base peak of each analyte. Positive findings were confirmed by
LC/MS/MS using the same mobile phase and column. This analytical procedure allows
for the detection of low levels of flunitrazepam and metabolites in biofluids. It
is useful for ascertaining the role of flunitrazepam in cases of drug-facilitated
sexual assault.
PMID- 11005192
TI - Parentage testing on blood crusts from firearms projectiles by DNA typing settles
and insurance fraud case.
AB - We describe a case of a fraudulent insurance claim. The family of an adult white
male (DLF) notified the police of their son's disappearance. After a few weeks, a
corpse that presented characteristics similar to those of the DLF was found in
advanced stages of decay and was identified by the family as being DLF. The
family then filed a claim for the life insurance that DLF had taken out just
before he disappeared. Suspicions were raised about the identification of the
corpse, because it had been done only visually, and because the insurance policy
had been taken out just prior to DLF's disappearance. The insurance company
requested a postmortem examination for identification. As the corpse had been
cremated immediately after identification by the family, the biological material
that was encrusted on the two projectiles removed from the body was used for
analysis. The blood crusts provided enough genomic DNA for us to carry out PCR
base typing of HLA-DQA1, D1S80, HUMCSF1PO, HUMTPOX, HUMTH01, D3S1744, D12S1090,
D18S849, and amelogenin. Results from all loci typing from the corpse presumed to
be that of DLF were then compared with that of his alleged biological parents,
revealing genetic incompatibility.
PMID- 11005193
TI - A cause celebre: the so-called "ballpoint murder".
AB - Transorbital intracranial injuries are uncommon but classic ophthalmologic
traumas. This report describes a case of a woman who was found dead. Postmortem
examination revealed a Bic ballpoint which had penetrated her head through her
right eye. Detective forces believed a murder to be the most likely cause;
however, medical expert consultants indicated that a tragic accident was more
likely. The case and the results of crossbow test-firing on human cadavers are
presented.
PMID- 11005194
TI - Acute cerebellar hemorrhage in a patient with Klinefelter syndrome: XXY karyotype
obtained postmortem from cells from pericardial fluid.
AB - A case of Klinefelter syndrome and a spontaneous cerebellar hemorrhage in a 12
year-old boy is presented. Autopsy revealed that the hemorrhage was due to the
rupture of a dilated artery in an arteriovenous malformation in the right
cerebellar hemisphere. The small, undescended testes exhibited partial atrophy of
the seminiferous tubules. Postmortem chromosome analysis of cells from the
pericardial fluid demonstrated a 47, XXY karyotype. He had previous surgical
treatment for bilateral thumb polydactyly and patent ductus arteriosus. In
juvenile cases of sudden death with overlapping morphological dysgenesis,
postmortem karyotyping may provide important diagnostic information.
PMID- 11005195
TI - Periadventitial extracranial vertebral artery hemorrhage in a case of shaken baby
syndrome.
AB - We report a case of a two-month-old boy who became unresponsive in the sole
custody of his father. Resuscitation efforts on route to the hospital were able
to restore the infant's heart beat. However, neurologic function never recovered.
Autopsy revealed massive cerebral edema, recent subdural, and subarachnoid
hemorrhages, bilateral retinal hemorrhages, and cervical spine ligament
hemorrhages. Separation of individual cervical vertebrae showed extensive,
bilateral, periadventitial vertebral artery hemorrhages between C1 and C4, with
corresponding luminal compression of the vertebral arteries. The importance of
this previously unreported phenomena of periadventitial vertebral artery
hemorrhage in the setting of shaken baby syndrome is discussed.
PMID- 11005196
TI - A non-fatal case of intoxication with foxglove, documented by means of liquid
chromatography-electrospray-mass spectrometry.
AB - The non-fatal self-poisoning of a 36-year-old female patient, who ingested a
concoction of foxglove (Digitalis Purpurea), is presented. On the admission,
initial symptoms were nausea and vomiting, abdominal pain, and cardiovascular
shock with sinus bradycardia. Blood and urine were assayed for 17 cardiotonic
hetorosides, using a highly specific LC-MS procedure. Serum and urine specimens
were collected over five days and analyzed by liquid chromatography-electrospray
mass spectrometry (LC-ES-MS). This accurate procedure allowed the determination
of the digitalis glycosides and their metabolites in serum and urine. The serum
concentrations of digitalis glycosides were maximum on the first day (gitoxin
13.1 ng/mL, digitoxin 112.6 ng/mL, digitoxigenin 3.3 ng/mL, and digitoxigenin
mono-digitoxoside 8.9 ng/mL) and decreased over five days. We observed a peak
gitaloxin level (112.6 ng/mL) on the fifth day only. After administration of
atropine as well as dimeticone, alginic acid, and metoclopramide, health status
improved. The peak urine concentrations were reached at hour 30 and were
respectively 91.3 and 69.9 ng/mL for gitaloxin and digitoxin, while those of
digitoxigenin, digitoxigenin mono-digoxoside and gitoxin were lower (respectively
0.7, 1, and 5.6 ng/mL). The patient was discharged on the fifth day when there
were no residual symptoms.
PMID- 11005197
TI - Distribution of amplified fragment length polymorphism D1S80 alleles in a Saudi
Arabian population.
PMID- 11005198
TI - Gene frequencies for four hypervariable DNA loci in a Chilean population of mixed
ancestry.
PMID- 11005199
TI - Mitochondrial DNA HVI and HVII variation in a north-east Spanish population.
PMID- 11005200
TI - Commentary on Kayumov L, Pandi Perumal SR, Federoff P, Shapiro CM. Diagnostic
values of polysomnograph in forensic medicine. J Forensic Sci 2000 Jan;45(1):191
4.
PMID- 11005201
TI - Phenotypic differences at the HUMvWA locus amplified with different STR kits.
PMID- 11005202
TI - Regulation of sucrose metabolism in higher plants: localization and regulation of
activity of key enzymes.
AB - Sucrose (Suc) plays a central role in plant growth and development. It is a major
end product of photosynthesis and functions as a primary transport sugar and in
some cases as a direct or indirect regulator of gene expression. Research during
the last 2 decades has identified the pathways involved and which enzymes
contribute to the control of flux. Availability of metabolites for Suc synthesis
and 'demand' for products of sucrose degradation are important factors, but this
review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase
(SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases.
Recent progress has included the cloning of genes encoding these enzymes and the
elucidation of posttranslational regulatory mechanisms. Protein phosphorylation
is emerging as an important mechanism controlling SPS activity in response to
various environmental and endogenous signals. In terms of Suc degradation,
invertase-catalyzed hydrolysis generally has been associated with cell expansion,
whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes
(e.g., cell wall or storage products). Recent results indicate that SuSy may be
localized in multiple cellular compartments: (1) as a soluble enzyme in the
cytosol (as traditionally assumed); (2) associated with the plasma membrane; and
(3) associated with the actin cytoskeleton. Phosphorylation of SuSy has been
shown to occur and may be one of the factors controlling localization of the
enzyme. The purpose of this review is to summarize some of the recent
developments relating to regulation of activity and localization of key enzymes
involved in sucrose metabolism in plants.
PMID- 11005203
TI - Ascorbic acid in plants: biosynthesis and function.
AB - Ascorbic acid (vitamin C) is an abundant component of plants. It reaches a
concentration of over 20 mM in chloroplasts and occurs in all cell compartments,
including the cell wall. It has proposed functions in photosynthesis as an enzyme
cofactor (including synthesis of ethylene, gibberellins and anthocyanins) and in
control of cell growth. A biosynthetic pathway via GDP-mannose, GDP-L-galactose,
L-galactose, and L-galactono-1,4-lactone has been proposed only recently and is
supported by molecular genetic evidence from the ascorbate-deficient vtc 1 mutant
of Arabidopsis thaliana. Other pathways via uronic acids could provide minor
sources of ascorbate. Ascorbate, at least in some species, is a precursor of
tartrate and oxalate. It has a major role in photosynthesis, acting in the Mehler
peroxidase reaction with ascorbate peroxidase to regulate the redox state of
photosynthetic electron carriers and as a cofactor for violaxanthin de-epoxidase,
an enzyme involved in xanthophyll cycle-mediated photoprotection. The
hypersensitivity of some of the vtc mutants to ozone and UV-B radiation, the
rapid response of ascorbate peroxidase expression to (photo)-oxidative stress,
and the properties of transgenic plants with altered ascorbate peroxidase
activity all support an important antioxidative role for ascorbate. In relation
to cell growth, ascorbate is a cofactor for prolyl hydroxylase that
posttranslationally hydroxylates proline residues in cell wall hydroxyproline
rich glycoproteins required for cell division and expansion. Additionally, high
ascorbate oxidase activity in the cell wall is correlated with areas of rapid
cell expansion. It remains to be determined if this is a causal relationship and,
if so, what is the mechanism. Identification of the biosynthetic pathway now
opens the way to manipulating ascorbate biosynthesis in plants, and, along with
the vtc mutants, this should contribute to a deeper understanding of the proposed
functions of this multifaceted molecule.
PMID- 11005204
TI - Distribution of Tsc1 protein detected by immunohistochemistry in various normal
rat tissues and the renal carcinomas of Eker rat: detection of limited
colocalization with Tsc1 and Tsc2 gene products in vivo.
AB - We and others previously demonstrated that hereditary mutation and a subsequent
second hit in the rat homolog of tuberous sclerosis gene (Tsc2) are responsible
for Eker renal carcinomas (RC). In humans, alteration in the TSC2 gene is known
to cause the tuberous sclerosis complex (TSC) that results in hamartomatous
lesions in multiple organs, but the function of TSC2 is not fully understood. In
recent years, a second gene (TSC1) responsible for human TSC has been cloned, and
binding between TSC1 and TSC2 proteins was reported. In this study, to clarify
associations between Tsc proteins in vivo, the expression of Tsc1 protein was
detected by immunohistochemistry, and compared with Tsc2 expression. Tsc1 protein
was expressed in the nervous system and in many endocrine tissues, including
pancreatic islets, the parathyroids, testis, and ovary. Tsc1 was also detected in
the many epithelial tissues of organs, such as kidney, uterus, small and large
intestine, and liver. Our results indicate overlapping, but not identical, organ
distributions of Tsc1 and Tsc2 proteins. At the intracellular distribution,
double fluorescent immunolabeling allowed the determination that only a partial
portion of Tsc1 signals overlapped with Tsc2 in some organs. These results
suggest the existence of co-localizing and independent forms of Tsc proteins in
endogenous expressions. Additionally, relatively high expression of Tsc1 protein
was detected in RC in the Tsc2 mutant (Eker) rat.
PMID- 11005205
TI - Establishment of a novel endothelial target mouse model of a typhus group
rickettsiosis: evidence for critical roles for gamma interferon and CD8 T
lymphocytes.
AB - A mouse model of typhus rickettsiosis that reproduces the hematogenous
dissemination to the critical target organs, including brain, lungs, heart, and
kidneys, primary endothelial and, to a lesser degree, macrophage intracellular
rickettsial infection, and typical vascular-based lesions of louse-borne typhus
and murine typhus was established. Intravenous inoculation of C3H/HeN mice with
Rickettsia typhi caused disease with a duration of the incubation period and
mortality rate that were dependent on the infective dose of rickettsiae. Lethal
infection was associated with high concentrations of R. typhi in the lungs and
brain, despite a brisker humoral immune response to the rickettsiae than in the
sublethal infection. Gamma interferon and CD8 T lymphocytes were demonstrated to
be crucial to clearance of the rickettsiae and recovery from infection in
experiments in which specific monoclonal antibodies were administered to deplete
these components. Death of animals depleted of gamma interferon or CD8 T
lymphocytes was associated with overwhelming rickettsial infection demonstrated
by titers of infectious rickettsiae and by immunohistochemistry. An effective
antirickettsial immune response was associated with elevated serum concentrations
of IL-12 on Day 5 and increased secretion of IL-12 by concanavalin-A-stimulated
spleen cells on Day 5. Evidence for transient suppression of the immune response
consisted of marked reduction in the secretion of IL-2 and IL-12 by concanavalin
A-stimulated spleen cells on Days 10 and 15. This model offers excellent
opportunities for study of attenuation and pathogenetic mechanisms of typhus
rickettsiae, which are established biologic weapons of potential use in
bioterrorism.
PMID- 11005206
TI - Cytomegalovirus infection of the central nervous system stem cells from mouse
embryo: a model for developmental brain disorders induced by cytomegalovirus.
AB - Cytomegalovirus (CMV) is the most frequent infectious cause of developmental
disorders of the central nervous system (CNS) in humans. Infection of the CNS
stem cells seems to be primarily responsible for the generation of the brain
abnormalities. In this study, we evaluated the infectivity of murine CMV (MCMV)
in epidermal growth factor (EGF)-responsive CNS stem cells prepared from fetal
mouse brains, and studied the effect of infection on growth and differentiation
of the stem cells. The CNS stem cells were permissive for MCMV infection,
although MCMV replication was slower than in mouse embryonic fibroblasts. MCMV
infection inhibited the growth and DNA replication of the stem cells. A
clonogenic assay revealed that MCMV infection suppressed generation of colonies
from single stem cells. When uninfected stem cells were induced to differentiate,
a decrease in expression of the primitive neuroepidermal marker nestin was
observed by immunocytochemistry and flow cytometry, whereas expression of
neurofilament and glial fibrillary acidic protein (GFAP) were induced. In virus
infected CNS stem cells, nestin expression was retained, whereas the expression
of neurofilament was more severely inhibited than that of GFAP in these cells.
Two-color flow cytometry showed that differentiated glial precursor cells were
preferentially susceptible to MCMV infection. MCMV-infected and uninfected CNS
stem cells were transplanted into the neonatal rat brains. The reduced number of
infected stem cells were engulfed into the subventricular zone and expressed
GFAP, but did not migrate further, in contrast to the uninfected stem cells.
These results suggest that suppression of the growth of the CNS stem cells and
inhibition of the neuronal differentiation by CMV infection may be primary causes
of disorders of brain development in congenital CMV infection.
PMID- 11005207
TI - Lethal Mycobacterium bovis Bacillus Calmette Guerin infection in nitric oxide
synthase 2-deficient mice: cell-mediated immunity requires nitric oxide synthase
2.
AB - The role of nitric oxide (NO) in Mycobacterium bovis Bacillus Calmette Guerin
(BCG) infection was investigated using nitric oxide synthase 2 (nos2)-deficient
mice, because NO plays a pivotal protective role in M. tuberculosis infection. We
demonstrate that nos2-deficient mice were unable to eliminate BCG and succumbed
within 8 to 12 weeks to BCG infection (10(6) CFU) with cachexia and pneumonia,
whereas all infected wild-type mice survived. The greatest mycobacterial loads
were observed in lung and spleen. Nos2-deficient mice developed large granulomas
consisting of macrophages and activated T cells and caseous necrotic lesions in
spleen. The macrophages in granulomas from nos2-deficient mice had reduced acid
phosphatase activities, suggesting that NO is required for macrophage activation.
The absence of NOS2 affected the cytokine production of the Th1 type of immune
response, except IL-18. Serum amounts of IL-12p40 were increased and IFN-gamma
was decreased compared with wild-type mice. The lack of NOS2 resulted in an
overproduction of TNF, observed throughout the infection period. Additionally,
TNFR1 and TNFR2 shedding was altered compared with wild-type mice. Up-regulation
of TNF may be compensatory for the lack of NOS2. The late neutralization of TNF
by soluble TNF receptors resulted in heightened disease severity and accelerated
death in nos2-deficient mice but had no effect in wild-type mice. In conclusion,
the inability of nos2-deficient mice to kill M. bovis BCG resulted in an
accumulation of mycobacteria with a dramatic activation of the immune system and
overproduction of pro-inflammatory cytokines, which resulted in death.
PMID- 11005208
TI - Analysis of the IGF axis in preneoplastic hepatic foci and hepatocellular
neoplasms developing after low-number pancreatic islet transplantation into the
livers of streptozotocin diabetic rats.
AB - Preneoplastic hepatic foci have been demonstrated in liver acini, which drain the
blood from intraportally transplanted pancreatic islets in streptozotocin-induced
diabetic rats with mild persisting diabetes. In long-term studies of this animal
model, hepatocellular adenomas and carcinomas (HCC) developed after a sequence of
characteristic preneoplastic hepatic foci. In this experimental model, the local
hyperinsulinism is thought to have a causative role. Because insulin and the
insulin-like growth factor (IGF) axis are closely linked, an altered gene
expression of the IGF axis components is likely. Therefore, preneoplastic hepatic
foci and HCC were studied for the expression of IGF axis components. Glycogen
storing "early" preneoplastic hepatic foci were detectable several days after
pancreatic islet transplantation. Northern blot analysis, in-situ hybridization,
and immunohistochemical studies of these "early" lesions demonstrated increased
expressions of IGF-I and IGF binding protein-4 (IGFBP-4) in altered parenchymal
cells, and a decreased expression of IGFBP-1. IGF-II was not detected in these
preneoplastic foci. HCC arising in this model had decreased expressions of IGF-I
and IGFBP-4 but IGFBP-1 expression was not significantly altered. Some HCC showed
a more than 100-fold overexpression of IGF-II, whereas other tumors were
completely negative for IGF-II expression. Low IGF-I receptor expression was
detected in preneoplastic foci and adjacent nonaltered liver tissue. However, HCC
tissue consistently showed an increased IGF-I receptor expression, rendering
these tissues susceptible to the mitogenic effects of IGF. The altered gene
expression in glycogen-storing preneoplastic hepatic foci, especially the up
regulation of IGF-I and IGFBP-4 with the down-regulation of IGFBP-1, resemble the
insulin-dependent regulation of these components in normal rat hepatocytes. These
data agree with previous studies demonstrating a correspondence of the focal
character, morphology, and enzyme pattern of preneoplastic hepatic foci with
insulin effects on hepatocytes. The development from preneoplastic foci to HCC
may be driven by insulin itself and/or an altered IGF axis component or yet
unidentified factors.
PMID- 11005209
TI - Suppression of Fas expression and down-regulation of Fas ligand in highly
aggressive human thyroid carcinoma.
AB - The Fas-FasL system seems to mediate thyrocyte death in Hashimoto's thyroiditis.
In thyroid cancer, down-regulation of bcl-2 seems to alter apoptosis control. We
compared the expression of immunoreactive Fas and FasL in normal thyroid with
that of tumors ranging from benign to highly aggressive. Fas is essentially not
expressed in normal thyrocytes, whereas FasL is expressed in approximately one
third of cases. Expression of both markers is significantly up-regulated in
adenoma and in well-differentiated papillary and follicular carcinoma. In
contrast, Fas is suppressed and FasL is strongly reduced in the most aggressive
histological variants (poorly differentiated and undifferentiated carcinoma).
Immunohistochemistry findings have been confirmed by analysis of Fas-FasL mRNA
transcripts. In vitro studies showed that the Fas receptor of thyroid tumor cells
was functional, because apoptosis was induced by an agonistic Fas antibody. Fas
expressing and Fas-resistant mammary cell lines were used as specificity
controls. Together with our previous data inversely relating bcl-2 expression and
thyroid tumor grade, the present findings further indicate that apoptotic
pathways are altered in thyroid neoplasia. Thus, the Fas-FasL system may
represent a marker of tumor aggressiveness.
PMID- 11005210
TI - Expression and function of X chromosome-linked inhibitor of apoptosis protein in
Sjogren's syndrome.
AB - Apoptotic cell death in acinar and ductal epithelial cells is thought to play an
important role in the development of salivary gland dysfunction in patients with
Sjogren's syndrome (SS). We examined the expression of anti-apoptotic molecules
in salivary glands from patients with SS. The labial salivary glands from six
human T-cell leukemia virus (HTLV)-I-seronegative and eleven HTLV-I-seropositive
SS patients were analyzed by immunohistochemistry. In vitro experiments were
performed with a human salivary gland cell line (HSG cells). Immunohistologic
analyses revealed that Bcl-2 and Bcl-x were preferentially expressed in salivary
infiltrating mononuclear cells more than acinar and ductal epithelial cells. In
contrast, strong X chromosome-linked inhibitor of apoptosis protein (XIAP)
expression was evident in both acinar and ductal epithelial cells. The pattern of
expression of these anti-apoptotic molecules was similar in both HTLV-I
seropositive and HTLV-I -seronegative SS patients. Western blot analysis
confirmed expression of XIAP in cultured HSG cells. The expression of XIAP in HSG
cells was increased by IL-1beta, TGF-beta1, or IL-10. However, XIAP expression
was down-regulated by TNF-alpha, which induced apoptotic cell death of HSG cells
with an increase in caspase-3 activity. These effects of TNF-alpha in HSG cells
were antagonized by IL-1beta, TGF-beta1, or IL-10. Our results suggest that XIAP
is important in regulating apoptotic cell death of acinar and ductal epithelial
cells in patients with SS.
PMID- 11005211
TI - An immunocytochemical and in situ hybridization analysis of annexin 1 expression
in rat mast cells: modulation by inflammation and dexamethasone.
AB - The presence and localization of the anti-inflammatory protein annexin 1 (also
known as lipocortin 1) in perivenular rat mast cells was investigated here. Using
the rat mesenteric microvascular bed and a combination of morphologic techniques
ranging from immunofluorescence to electron microscopy analyses, we detected the
presence of annexin 1 in discrete intracellular sites, both in the nucleus and in
the cytoplasm. In resting mast cells, most of the protein pool (approximately 80%
of the cytosolic portion) was localized to cytoplasmic granules. In agreement
with other cell types, treatment of rats with dexamethasone (0.2 mg/kg, ip)
increased annexin 1 expression in mast cells, inducing a remarkable appearance of
clusters of protein immunoreactivity. This effect was most likely the result of
de novo protein synthesis as determined by an increase in mRNA seen by in situ
hybridization. Triggering an ongoing experimental inflammatory response (0.3 mg
of carrageenin, ip) increased annexin 1 mRNA and protein levels. In conclusion,
we report for the first time the localization of annexin 1 in connective tissue
mast cells, and its susceptibility not only to glucocorticoid hormone treatment,
but also to an experimental acute inflammatory response.
PMID- 11005213
TI - FISH analysis of gene aberrations (MYC, CCND1, ERBB2, RB, and AR) in advanced
prostatic carcinomas before and after androgen deprivation therapy.
AB - Genetic mechanisms leading to androgen-independent growth in advanced prostatic
carcinomas (PC) are still poorly understood. Analysis of genes potentially
involved in the regulation of tumor cell proliferation and apoptosis might confer
better insight into this process and might lead to improved therapeutic
strategies. Fluorescence in situ hybridization (FISH) analysis of dissociated
nuclei with DNA probes for MYC (8q24)/#8, cyclin D1 gene (CCND1; 11q13)/#11,
ERBB2 (17q13)/#17, the androgen receptor gene (AR; Xq12)/#X, and the
retinoblastoma gene (RB; 13q14) was applied to formalin-fixed tissue from 63
patients with advanced PC after androgen deprivation therapy (ADT); matched tumor
tissue before ADT was also available in 22 of these cases. The cut-points used
were: "increased copy number," > or = 30% of all nuclei with increased FISH
signals (centromere and/or gene); "amplification," > or = 15% of nuclei with
"increased gene copy number." CCND1 and MYC gene "amplifications" were present
before ADT in 25% and 33% of the cases, respectively; the frequency of these
"amplifications" increased to 37% and 57% after ADT. Loss of the RB gene was
nearly four times more frequent after ADT than before therapy (22% versus 6%). AR
and ERBB2 gene "amplifications" occurred only after ADT in 36% and 30% of cases,
respectively. With the exception of the AR gene, the copy number increase was
low. After treatment, MYC and AR gene "amplifications" correlated with the
proliferation rate (Ki-67/MIB1 index; p = 0.01 and p = 0.04), whereas ERBB2
"amplifications" were associated with increased apoptotic index (PCD/TUNEL; p =
0.016). However, no correlation between FISH results and clinical follow-up could
be established. FISH analysis of genes putatively involved in PC progression
revealed characteristic patterns of aberrations in advanced PC before and after
ADT. Distinct changes in gene copy number before and after therapy suggests
possible involvement of these genes in the escape from androgen control.
PMID- 11005212
TI - The tyrosine kinase inhibitor tyrphostin AG 126 reduced the development of
colitis in the rat.
AB - Inflammatory bowel disease is characterized by oxidative and nitrosative stress,
leukocyte infiltration, up-regulation of the expression of intercellular adhesion
molecule-1 (ICAM-1), and up-regulation of P-selectin in the colon. Here we
investigate the effects of the tyrosine kinase inhibitor, Tyrphostin AG 126, in
rats subjected to experimental colitis. Colitis was induced in rats by
intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Rats
experienced hemorrhagic diarrhea and weight loss. Four days after administration
of DNBS, the mucosa of the colon exhibited large areas of necrosis. Neutrophil
infiltration (determined by histology as well as an increase in myeloperoxidase
activity in the mucosa) was associated with up-regulation of ICAM-1 and P
selectin, as well as high tissue levels of malondialdehyde. Immunohistochemistry
for nitrotyrosine and poly(ADP-ribose) polymerase showed an intense staining in
the inflamed colon. Staining with an anti-COX-2 antibody of sections of colon
obtained from DNBS-treated rats showed a diffuse staining of the inflamed tissue.
Furthermore, expression of inducible nitric oxide synthase was found mainly in
macrophages located within the inflamed colon of DNBS-treated rats. Tyrphostin AG
126 (5 mg/kg daily ip) significantly reduced the degree of hemorrhagic diarrhea
and weight loss caused by administration of DNBS. Tyrphostin AG 126 also caused a
substantial reduction of (1) the phosphorylation of tyrosine residues of proteins
(immunoblots of inflamed colon), (2) the degree of colonic injury, (3) the rise
in myeloperoxidase activity (mucosa), (4) the increase in the tissue levels of
malondialdehyde, (5) the increase in staining (immunohistochemistry) for
nitrotyrosine and poly(ADP-ribose) polymerase, as well as (6) the up-regulation
of ICAM-1 and P-selectin caused by DNBS in the colon. Thus, we provide the first
evidence that the tyrosine kinase inhibitor Tyrphostin AG126 reduces the degree
of colitis caused by DNBS.
PMID- 11005214
TI - Expression of structurally unaltered androgen receptor in extramammary Paget's
disease.
AB - Extramammary Paget's disease (EMPD) is an uncommon neoplasm of the skin that
shows differentiation to an apocrine sweat gland. Although we previously showed
that erbB-2 overexpression may play a part in the progression of EMPD, molecular
genetic defects underlying the development of EMPD are poorly understood. In the
study described here, we examined androgen receptor expression and gene
alterations in 30 cases of EMPD without internal malignancy. Immunohistochemistry
revealed that 24 of 30 (80%) cases of EMPD variably expressed nuclear androgen
receptor. Semi-quantitation of receptor content by scoring immunostained sections
showed no difference between in situ (n = 17) and invasive (n = 13) EMPD tumors.
Androgen receptor expression was also observed in four of six lymph node
metastases. In these lymph nodes, expression of androgen receptor mRNA was
confirmed by reverse transcriptase-polymerase chain reaction. Direct sequencing
of exon 2 through exon 8, which encodes DNA- and hormone-binding domains of the
androgen receptor gene, revealed no mutation in any of the 10 advanced stage
tumors. Neither amplification nor deletion of the androgen receptor gene locus
was detected by dual color fluorescence in situ hybridization analysis in 14
tumors. The present findings showing frequent expression of structurally
unaltered androgen receptor in an advanced stage of EMPD may provide a rational
basis for hormone therapy, which is widely used in the treatment of metastatic
prostate cancer and androgen receptor-positive breast cancer recurrence.
PMID- 11005215
TI - A novel method for the establishment of a pure population of nontransformed human
intestinal primary epithelial cell (HIPEC) lines in long term culture.
AB - A novel method for generating nontransformed human intestinal primary epithelial
cell (HIPEC) lines in an in vitro culture system is reported here. Although
several groups have reported the development of nontransformed intestinal
epithelial cells (IEC) lines (Deveney et al, 1996; Latella et al, 1996; Pang et
al, 1996; Perreault and Beaulieu, 1998), it still had been difficult to find an
optimal condition to generate a pure population of nontransformed IEC in long
term cultures. It was hypothesized that an appropriate growth factor/cytokine
milieu that would mimic the physiological microenvironment might favor the
survival of the isolated cells and might play a critical role in epithelial cell
growth. To test this hypothesis, isolated progenitor/crypt cells were cultured in
collagen-coated petri dishes in the presence of mucosal tissue-derived growth
factor containing culture supernatants (14-18 hours) and a combination of
hormonal supplements. Cell attachment and growth was observed within 24 hours and
confluent monolayers were seen between 7 and 12 days. Immunofluorescence staining
and flow cytometric analysis of the cells demonstrated positive staining with
anti-cytokeratin-18 antibody confirming their epithelial origin. The
reproducibility of the method has been confirmed by establishing a number of
HIPEC lines from various segments of the gastrointestinal tract. This novel
method of HIPEC line generation, which maximizes the similarity of the ex vivo
culture system to in vivo conditions, will serve as a valuable tool for the
establishment of a large number of HIPEC lines (intestinal epithelial cell bank)
and for subsequent use in studies of the immunological/physiological epithelial
function in the intestine.
PMID- 11005216
TI - RT-PCR from archival single cells is a suitable method to analyze specific gene
expression.
PMID- 11005217
TI - Sociocultural perspectives on physical activity in the lives of older African
American and American Indian women: a cross cultural activity participation
study.
AB - Illuminating the diversity and sociocultural specificity of women's experiences
may be important if healthy lifestyles and quality of life are to be achieved.
The incidence of cardiovascular disease linked to physical inactivity is high
among African American and American Indian women. If more is understood about the
experience of physical activity involvement, healthier living might be
encouraged. Therefore, the purpose of this study was to explore the sociocultural
meanings of physical activity for older (over the age of 40 years) African
American and American Indian women who participated in the Cross Cultural
Activity Participation Study (CAPS). Through qualitative in-depth interviews, we
explored how sociocultural perspectives are related to perceptions about physical
activity. Gender and other sociocultural factors influenced physical involvement
on a continuum from negligible to significant. Both groups interviewed showed
evidence that opportunities for physical activity in their free time did not
always exist for them. For African American women, history and daily living
issues were important factors limiting their involvement. Marginality limited
American Indian women, but their cultural pride was often a source of physical
activity. The juxtaposition of cultural and personal values emerged as a
determinant of physical activity involvement among the women in this study. A
further expansion of cultural and personal life situation perspectives is
recommended to help understand the complex dimensions of physical activity as it
relates to healthy living.
PMID- 11005218
TI - Assessment of intimate partner violence among high-risk postpartum mothers:
concordance of clinical measures.
AB - Intimate partner violence (IPV) may be a more common problem than some conditions
for which pregnant women are routinely screened and evaluated. Screening for IPV
necessitates competence in assessment using reliable and valid instruments. The
present study examines the concordance in the prevalence of abuse reported by 436
high-risk postpartum mothers using (1) a single item hospital screen, (2) trained
paraprofessional interviewer-interview format, and (3) the Conflict Tactics Scale
(CTS), a standardized research instrument. The hospital screen identified 4% of
the sample as scared, threatened or hurt, the Family Stress Checklist (FSC)
identified 16.9% of the fathers as having severe potential for violence, and the
CTS identified 18.6% of the sample as victims of physical abuse at the hands of
the baby's father. There was minimal overlap between the ratings of severe
potential for violence and the occurrence of violence as assessed by the CTS.
Study findings illustrate the inadequacy of current procedures for detecting IPV
with high-risk populations and highlight the need to develop reliable and valid
assessments that can be easily utilized in the hospital setting.
PMID- 11005219
TI - Mothers with HIV/AIDS and their children: disclosure and guardianship issues.
AB - For many mothers living with HIV/AIDS, whether, when, and how to disclose their
HIV diagnosis to their children and arranging for future care are important
although agonizing issues. Due to the increasing number of children who lose
their mothers to AIDS and the dearth of empirical information about them, these
issues are increasingly important to research. This study of 188 HIV-positive
mothers and their 267 children of minor age in New York City revealed that only
half the mothers had disclosed their HIV diagnosis to at least one of their
children and only 57% had made formal plans for the children's care. As expected,
older children were more likely to be informed than younger children. Contrary to
some previous research, maternal disclosure was not related to ethnicity,
advanced illness, improved psychological well-being, or greater or more
satisfying social support resources. Implications for future research and
provision of services to this group of women are discussed.
PMID- 11005220
TI - Differences in fertility patterns between urban and rural women in Washington
State, 1983-1984 to 1993-1994.
AB - We use data on Washington State abortions and births for 1983-1984 and 1993-1994
to analyze trends for urban and rural women, using the demographic measures total
abortion and total fertility rates. These express pacing of childbearing in a
single number which is simple to calculate and interpret, and is age
standardized. We find significant urban-rural differences. Total abortion rates
decline and total fertility rates increase in both areas. However, the relative
magnitudes of pacing decreases in abortions for rural women and increases in
births for urban women are striking. The demographic measures are useful
interpretive tools, and can be applied to a broad range of questions.
PMID- 11005221
TI - The relationship of tamoxifen with dementia, depression, and dependence in
activities of daily living in elderly nursing home residents.
AB - OBJECTIVES: To evaluate the association between tamoxifen treatment and the
prevalence of Alzheimer's disease, other dementias, depression, and the levels of
dependence in activities of daily living (ADL) in elderly, nursing home
residents. PARTICIPANTS: 93,031 women, at least 65 years old, whose data were
part of the 1993 New York State MDS, and for whom there was documentation of
treatment with at least one medication. SETTING: New York State long-term care
facilities. DESIGN: Cross-sectional study via secondary analysis of 1,385 matched
sets of residents. Each set included one resident who received tamoxifen
treatment and up to four residents who did not. MEASUREMENTS: Included age,
ethnicity, tamoxifen treatment, hormone replacement therapy, depression, levels
of dependence in ADL and in cognitive skills for daily decision-making, and
documentation of Alzheimer's disease and other dementias. RESULTS: Women
receiving tamoxifen were less likely to have a diagnosis of Alzheimer's disease
documented on the MDS (odds ratio: 0.674; 95% confidence interval: 0.551-0.823),
were significantly more independent in bed mobility, eating, toileting (in each
case P < 0.0001), personal hygiene (P = 0.0155), dressing (P = 0.0015),
transferring (P = 0.0006), locomotion (P = 0.0016), and they had better cognitive
skills for daily decision-making (P < 0.0001). They were, however, 42% more
likely to have a MDS diagnosis of depression (P < 0.0001). All tests of
statistical significance are two-sided. CONCLUSION: In this population, tamoxifen
was associated with a higher level of independence in ADL and decision-making.
While the MDS also suggested a relationship of tamoxifen with a lower prevalence
of Alzheimer's disease, there seemed to be an increased prevalence of depression
among treated women. The findings of this cross-sectional study could be
evaluated in the randomized clinical trial that has just begun, and that will
compare tamoxifen and raloxifene treatments.
PMID- 11005222
TI - Exotic dancing and health.
AB - The health and safety of women who work as exotic dancers are firmly embedded
within the social organization of the strip club and the broader social, economic
and political context of the work of exotic dancing. Exotic dancers in this study
expressed health concerns associated with: the effects of costuming and
appearance requirements; dirty work environments; problems due to stigmatization,
sexual harassment and assault; and police disinterest or victim blaming. The
balance between benefits and hazards related to exotic dancing is influenced not
only by the personal choices made by dancers, but also by the organization of the
strip club and the broader context within which exotic dancing takes place.
PMID- 11005223
TI - Cell proliferation in the developing rat pineal gland. A bromodeoxyuridine
immunohistochemical study.
AB - The immunohistochemical detection of bromodeoxyuridine (BrdU) was used to study
the cell proliferation in the developing rat pineal gland, from the appearance of
pineal primordium in the embryonic day 15 (E15) until 30 days after birth. The
results showed three different proliferative phases. From E15 to E21, the pineal
gland shows a phase of rapid proliferation. The second phase corresponds to the
first postnatal week, in which the number of labeled cells per surface unit
decreases suddenly to values between 20% to 10% of those of embryonic period.
From the second postnatal week onwards, the number of BrdU-positive cells
progressively decreases.
PMID- 11005224
TI - Glycogen autophagy in newborn rat hepatocytes.
AB - Glycogen autophagy in newborn rat hepatocytes was studied by using enzyme
determinations and electron microscopy. Cyclic AMP induced glycogen autophagy in
these cells. Glycogen-hydrolyzing acid glucosidase activity increased whereas
acid mannose 6-phosphatase activity decreased in the liver of these animals.
Parenteral glucose, which prevents postnatal glucagon secretion and tissue cyclic
AMP elevation, and propranolol which antagonizes cyclic AMP, inhibited glycogen
autophagy. Glucosidase activity decreased and phosphatase activity increased.
These findings raise the possibility that cyclic AMP-induced autophagic
mechanisms in newborn rat hepatocytes are associated with changes in the activity
of acid mannose 6-phosphatase.
PMID- 11005225
TI - Calbindin D-28k immunoreactive nerve fibers in the carotid body of normoxic and
chronically hypoxic rats.
AB - The distribution and ultrastructural characteristics of calbindin D-28k
immunoreactive nerve fibers were examined in the carotid body of the normoxic
control rats by light and electron microscopy, and the abundance of calbindin D
28k fibers in the carotid body was compared in normoxic and chronically hypoxic
rats (10% O2 and 3.0-4.0% CO2 for 3 months). Calbindin D-28k immunoreactivity was
recognized in nerve fibers within the carotid body. Calbindin D-28k
immunoreactive nerve fibers appeared as thin processes with many varicosities.
They were distributed around clusters of glomus cells, and around blood vessels.
Immunoelectron microscopy revealed that the calbindin D-28k immunoreactive nerve
terminals are in close apposition with the glomus cells, and membrane
specialization is visible in some terminals. Some dense-cored vesicles in the
glomus cells were aggregated in this contact region. The chronically hypoxic
carotid bodies were found to be enlarged several fold, and a relative abundance
of calbindin D-28k fibers was lesser than in the normoxic carotid bodies. When
expressed by the density of varicosities per unit area of the parenchyma, the
density of calbindin D-28k fibers associated with the glomus cells in chronically
hypoxic carotid bodies was decreased by 70%. These immunohistochemical findings
indicate a morphological basis for involvement of calcium binding protein in the
neural pathway that modulates carotid body chemoreception.
PMID- 11005226
TI - Expression of a neu/c-erbB-2-like product in neuroendocrine cells of mammals.
AB - The neu/c-erbB-2 oncogene encodes a 185 kDa protein closely homologous to the
epidermal growth factor receptor. The protein product (p185) is a glycoprotein
with an external domain and an internal domain with tyrosine kinase activity.
Amplification and/or overexpression of p185 is related to several human
adenocarcinomas. Subsequent studies demonstrated its presence in certain
neuroendocrine (NE) neoplasms, including phaeochromocytomas, insulinomas and
medullary thyroid carcinomas. However, relatively little is known about its role
in normal cell growth regulation and development. Therefore, our objective was to
determine whether neu/c-erbB-2 was expressed in normal NE tissues of different
mammals, specially in humans, as it was in their neoplasms. We have examined by
immunohistochemistry different endocrine glands (thyroid, pancreas, suprarrenal
and hypophysis) and the small intestine of human beings, rats and guinea pigs,
using two polyclonal antibodies raised against the intracytoplasmic part of the
protein, and specific antigen absorption controls. We have found that a neu/c
erbB-2-like product occurs in all normal NE tissues examined: C cells of the
thyroid gland, chromaffin cells of the adrenal medulla, pancreatic islets,
enteroendocrine cells of the small intestine and, finally, scattered cells of the
adenohypophysis, according to a typical granular immunohistochemical pattern. Our
results indicate that normal NE cells share a new common antigen in their
cytoplasms, a neu/c-erbB-2-like product, with a similar immunostaining pattern to
that presented by the neoplasms derived from them.
PMID- 11005227
TI - Immunohistochemical detection of metallothionein in carcinomatous and normal
human gastric mucosa.
AB - Utilising a specific monoclonal mouse antibody (E9), metallothionein (MT)
expression has been immunohistochemically investigated in 112 formalin-fixed
paraffin-embedded surgical gastric samples, 38 of which were early carcinomas
(EGC) and 74 advanced ones (AGC); clinico-pathological details and follow-up data
(ranging from 3 to 197 months, mean 60.5 months) were available. Eighty-nine
portions of gastric mucosa adjacent to examined carcinomas (transitional mucosa)
were also analysed; in addition, 22 biopsies of normal gastric mucosa were
studied as tissue control. The MT immunoreactivity was evaluated by staining and
intensity-distribution scores. A various MT positivity was appreciable in the
cytoplasm and nucleus of antrum or body gastric epithelial cells in 100% of
normal control biopsies. 75/112 (67%) gastric carcinomas showed MT
immunoreactivity with a significant lower expression in AGC. No relationships
were encountered between MT immunostaining and clinico-pathological data; in
addition, no difference in the Kaplan-Meier survival curves of patients with
various MT expression was achieved. When the transitional mucosa was examined,
84/89 (94%) samples were stained although the immunoreaction was not always
concordant with that encountered in adjacent carcinomatous elements. The
significant statistical decrease of MT scores observed by us moving from normal
to neoplastic gastric mucosa allows us to exclude the hypothesis of an
overexpression of MT in gastric carcinomas.
PMID- 11005228
TI - Changes of superoxide dismutase, catalase and glutathione peroxidase in the
corneal epithelium after UVB rays. Histochemical and biochemical study.
AB - In this study, the effects of UVA and UVB rays on antioxidant enzymes (superoxide
dismutase, glutathione peroxidase, catalase) were examined in the corneal
epithelium. The corneas of albino rabbits were irradiated with a UV lamp
generating UVA (365 nm wavelength) or UVB rays (312 nm wavelength), 1 x daily for
5 min, from a distance of 0.03 m, over 4 days (shorter procedure) or 8 days
(longer procedure). In contrast to UVA rays, which did not evoke significant
disturbances, UVB rays changed the activities of antioxidant enzymes. The longer
repeated irradiation with UVB rays was performed, the deeper the observed
decrease in antioxidant enzymes. The shorter procedure evoked a more profound
decrease of glutathione peroxidase and catalase (the enzymes cleaving hydrogen
peroxide) than of superoxide dismutase, an enzyme scavenging superoxide radical
and producing hydrogen peroxide during the dismutation reaction of a superoxide
free radical. This may contribute to an insufficient hydrogen peroxide cleavage
at the corneal surface and danger to the cornea from oxidative damage. After the
longer procedure (UVB rays), the activities of all antioxidant enzymes were very
low or completely absent. In conclusion, repeated irradiation of the cornea with
UVB rays evokes a deficiency in antioxidant enzymes in the corneal epithelium,
which very probably contributes to the damage of the cornea (and possibly also
deeper parts of the eye) from UVB rays and the reactive oxygen products generated
by them.
PMID- 11005229
TI - Potential use of spectral image analysis for the quantitative evaluation of
estrogen receptors in breast cancer.
AB - Evaluation of estrogen receptor (ER) content is an important factor in the choice
of therapy and prognosis of breast cancer patients. In this study, we demonstrate
a new spectral image analysis technique for objective and quantitative
evaluations of stained specimens. The SpectraCube system was used to analyze
nuclear antigens in thirteen cases of breast cancer stained by the
immunoperoxidase method with hematoxylin counterstain. Spectral imaging
segregated the spectrum of diaminobenzidine (DAB) from the background color of
hematoxylin and a spectral index was calculated. The spectral index essentially
agreed with the pathologist's index (on a scale of 0 to 3) in seven out of the
thirteen cases. A substantial number of ER positive pixels was detected in the
two cases scored as 0 by the pathologist's index. In a test case scored as 1 by
the pathologist's index we detected a significant number of pixels, representing
47% of the nuclei, with DAB-intensity values higher than the cut-off value of
1.2. These data suggest that spectral image analysis is a sensitive method
providing intensive information with high reproducibility. Our spectral imaging
method is highly flexible, enabling the user to define the spatial resolution of
the analyzed specimen by choosing the number of pixels per one nucleus.
PMID- 11005230
TI - Topographical difference of cytoskeletal organization in smooth muscle cells of
rat duodenum revealed by quick-freezing and deep-etching method.
AB - The sarcolemmal domain of rat duodenal smooth muscle cells includes caveolae and
associated cytoskeletal or filamentous elements. We have used the quick-freezing,
deep-etching method to examine the three dimensional relationships between these
components. Replica membranes for separated strips of rat duodenal muscle layers
were routinely prepared after extraction soluble proteins from cytoplasm and
extracellular matrix. As results, 1) cytoskeletal elements in smooth muscle cells
consisted mainly of striated thin filaments; 2) thin filaments were connected
with some plasma membranes through filaments associated with the sarcolemma,
which formed fine network structures beneath the sarcolemma; 3) many bridging
structures between the filaments associated with the sarcolemma and the
extracellular matrix were frequently detected in the plasma membrane; and 4)
compact filaments associated with the sarcolemma almost disappeared near the
caveolae, and only thin filaments were anchored to their neck parts. The special
arrangement of the cytoskeletal components, which is probably necessary for the
intestinal motility, characterizes the topographical difference of the smooth
muscle sarcolemma.
PMID- 11005231
TI - Suppressive effect of rebamipide, an antiulcer agent, against activation of human
neutrophils exposed to formyl-methionyl-leucyl-phenylalanine.
AB - Rebamipide, an antiulcer agent, has been shown to be able to prevent gastric
mucosal injury resulting in part from activation of neutrophils. The mechanism of
its suppressive action, however, remains to be established. The present study
aimed to determine the effect of rebamipide on activation of isolated human
neutrophils and to identify the signal transduction pathway involved in its
regulation. In unstimulated cells, alkaline phosphatase activity was found
residing in short rod-shaped intracellular granules. Upon stimulation with a
chemotactic peptide formyl-methionyl-leucyl-phenylalanine, the granules fused to
form elongated tubular structures and spherical vacuoles. Rebamipide inhibited
reorganization of alkaline phosphatase-containing granules along with
upregulation of alkaline phosphatase activity and CD16, a marker of the granules.
It also suppressed chemotaxis, an increase in intracellular calcium ion
concentration, and NADPH oxidase activation in cells stimulated with formyl
methionyl-leucyl-phenylalanine. In contrast, the drug showed no inhibitory action
toward upregulation of alkaline phosphatase activity and CD16, and activation of
NADPH oxidase in cells stimulated with phorbol myristate acetate, an activator of
protein kinase C. These findings demonstrate that rebamipide exerts a broad
spectrum of suppressive actions toward biological functions of human neutrophils
stimulated with formyl-methionyl-leucyl-phenylalanine, but not with phorbol
myristate acetate, and suggest that the upstream point of protein kinase C is the
signal transduction pathway involved in its regulation.
PMID- 11005232
TI - Dendritic cells and interleukin-2: cytochemical and ultrastructural study.
AB - The aim of the present study was to verify the effect of IL-2 on dendritic cell
(DC) differentiation. Various cytokines have been indicated as factors inducing
DC differentiation, but no data about the interleukin-2 (IL-2) effect on DC
differentiation have been reported. Monocytes isolated from peripheral blood were
treated in vitro with the following factors: IL-2, IL-4, GM-CSF and G-CSF alone
or in combination. Morphological (also ultrastructural) and cytochemical
observations were carried out starting from 3 to 21 days of treatment. The
results indicate that the differentiation of cells showing dendritic pattern is
related to the presence of IL-2. Moreover a synergic effect of IL-2 and GM-CSF
was observed. The enzymatic features changed with the culture time: before the
differentiation into DC, the stimulated cells expressed the typical pattern of
monocytes. On the contrary, at advanced stage of differentiation, some enzyme
activities changed and in terminally differentiated dendritic cells the reactions
for peroxidase and serine esterase were negative. Considering the morphological
features, the ability to interact with lymphocytes and the enzymatic pattern
observed, we suppose that IL-2 may act as a maturative factor rather than as a
growth factor in the DC differentiation.
PMID- 11005233
TI - Age-related morphometric changes in the pineal gland. A comparative study between
C57BL/6J and CBA mice.
AB - Relatively little is known about the effects of melatonin on the aging of the
pineal, the organ which is the main place for synthesis of this hormone. Using
simple morphometric methods, some parameters of the pineal gland, such as total
volume, number of pinealocytes and pinealocyte volume were estimated in two mice
strains: normal CBA and melatonin-deficient C57BL/6J. Two age groups, 6 weeks and
10 months, were studied in order to evaluate possible differential age-related
changes between both strains. Pineals of both strains have similar morphometric
and morphological features at 6 weeks of age. This suggests that pineal
development, which has already concluded at 6 weeks of age, is not affected by
the absence of melatonin synthesis in the pinealocytes. Later on, CBA pineal
showed an increase in size caused by cellular hypertrophy. In contrast, the
C57BL/6J pineal volume decreased by loss of pinealocytes in the same period of
time. Semithin sections analysed by light microscopy did not show that this cell
death was evident in the C57BL/6J strain at any of the ages studied. Thus, a
gradual loss of pinealocytes could be hypothesised in these pineals. These
results suggest that pineal melatonin could have a role in the maintenance of
pinealocyte viability and the increase of pineal size which takes place after
development. The abnormal pattern observed in the C57BL/6J pineal should be taken
into account in future studies on this gland.
PMID- 11005234
TI - Intrinsic innervation in the intestine of the lizard Podarcis hispanica.
AB - The aim of this study was the description of the morphology and distribution of
nerve structure elements in the intestine of the lizard Podarcis hispanica using
different histochemical methods; namely acetylcholinesterase (AChE), formol
induced fluorescence for catecholamines (FIF), nicotinamide adenine dinucleotide
phosphate diaphorase (NADPH-d), and immunohistochemistry for vasoactive
intestinal peptide (VIP), as well as substance P (SP) and electron microscopy.
The AChE method showed fibres in the myenteric and submucosal plexus, with a
higher fibre density in the large intestine. The highest number of related
neurons was located in the myenteric plexus ganglia. Noradrenergic innervation
was distributed through the myenteric and submucosal plexus, and also around
blood vessels, with the highest fibre density in the large intestine. VIP
immunohistochemistry showed a wide distribution of positive fibres throughout the
intestine, although the highest density was again detected in the large
intestine. Small positive cells for VIP were located at internodal segments in
the plexus. SP labeling, although subtle, was present all along the intestine. It
showed delicate varicose nets and few fibres innervating blood vessels. Small
positive cells for SP were located in the large intestine. The indirect method to
detect nitric oxide (NO)-producing system showed neural cells in the myenteric
plexus ganglia of the large intestine. Electron microscopy showed ganglion
neurons with scattered chromatin condensations, glial cells with higher electron
density, and axons with varicosities occupied by different vesicles. We also
identified certain cells as interstitial cells of Cajal due to their
ultrastructural features. They were mostly located in the region of the myenteric
plexus.
PMID- 11005235
TI - Nuclear and cytoplasmic lectin receptor sites in rat Py1a osteoblasts.
AB - The intracellular distribution of lectin receptor sites was studied in the rat
Pyla osteoblasts using immunofluorescence at the confocal microscopy level. This
immortalized cell line was found to represent a satisfactory model to study the
occurrence and distribution of sugar moieties. Our data showed distinct affinity
patterns of lectins recognizing different terminal or internal sugar residues.
For some lectins, the binding patterns appeared to be cell cycle-independent,
whereas for PNA the cell cycle greatly influenced the nuclear binding. By
combining lectin affinity with sialidase degradation and alcoholic saponification
the sialic acid acceptor sugars and derivatives were also visualized. In
particular, glycoconjugates with sialic acids linked to beta-galactose, and
mainly C4 acetylated, were located in the cytoplasm, while glycoconjugates
characterized by sialic acids linked to alpha-N-acetylgalactosamine, and devoid
of acetyl groups at C4, were almost exclusively found in the nucleus. The
comparison of lectin affinities, with and without prior glycosidase digestions,
allowed us to gain further insight into the chemical composition of
glycoconjugates that act as the lectin receptor sites that appeared to belong to
O- and N-linked glycoconjugates. The use of additional enzymatic treatments were
useful to better establish the localization of nuclear receptor sites and results
were compared with previous studies about endogenous and exogenous lectins in an
attempt to reconcile the association of lectins and sugars within the nucleus and
their possible involvement in modulation of cell proliferation and/or response to
chemical signals. The above digestions also provided information about the
cytoplasmic binding patterns.
PMID- 11005236
TI - Confocal evaluation of native and induced lectin binding contributes to
discriminate between lingual gland glycocomponents in quail.
AB - A confocal analysis was performed on the quail (Coturnix coturnix japonica)
lingual salivary glands where the carbohydrate chains were studied by lectin
histochemistry. For this purpose, appropriate FITC- and TRITC-conjugates were
used for double binding also accomplished with sialidase digestion. The
glycosidic components of the quail lingual salivary glands were found to be
heterogeneously distributed on the different secretory structures as well as on
the single secretory elements of each adenomere. The rostral portion of the
anterior lingual gland was found to only secrete neutral glycocomponents,
characterized by terminal beta-galactose, N-acetylgalactosamine and fucose
residues in contrast to the caudal portion that was shown to be extremely
heterogeneous and to produce sialylated glycoconjugates characterized by the
terminal sequences sialic acid-beta-galactose-N-acetylgalactosamine, sialic acid
beta-galactose-N-acetylglucosamine, and sialic acid-alpha-N-acetylgalactosamine
partly codistributed within secretory adenomeres. The posterior lingual gland was
observed to be the major contributor to the secretion of salivary mucins
containing sialoglycoconjugates with terminal sialic acid residues linked to beta
galactose-N-acetylgalactosamine or alpha-N-acetylgalactosamine often located in
distinct secretory elements.
PMID- 11005237
TI - Selective expression of lysyl oxidase (LOX) in the stromal reactions of broncho
pulmonary carcinomas.
AB - Lysyl oxidase (LOX) is the extracellular enzyme that initiates the main pathway
of collagen and elastin cross-linking. LOX has also been correlated with the ras
recision gene, a putative tumour suppressor isolated from revertants of ras
transformed fibroblasts. The present study investigates the potential correlation
of LOX-dependent matrix protein cross-linking in the stromal reaction of lung
carcinomas, with reference to the architecture of the main stromal reactions
accompanying the neoplastic breast tissues. A strong LOX expression was
associated with the hypertrophic scar-like stromal reaction found at the front of
tumour progression in squamous carcinomas, adenocarcinomas, large cell
carcinomas, or at sites of initial extense in bronchiolo-alveolar carcinomas. In
contrast, little or no LOX expression was found within the stromal reaction of
invasive carcinomas, small cell carcinomas, and neuro-endocrine carcinomas. The
significance of LOX expression and of the stromal reaction are discussed, in
light of data that associate LOX expression with tumours displaying a rather good
prognosis.
PMID- 11005238
TI - Morpho-histochemical study of the biological effects of sodium dodecyl sulphate
on the digestive gland of the Portuguese oyster.
AB - In the present work we have studied the effects on survival as well as
histopathological and histochemical alterations on the digestive gland of the
Portuguese oyster (Crassostrea angulata, Lmk.) induced by acute action of the
anionic tensioactive Sodium Dodecyl Sulphate (SDS) at different concentrations
(50, 100, 200 and 400 mg/L). Firstly, the LC 50 at 96 h was found to be 136 mg/L
SDS. Secondly we calculated the exposure time required for 50% mortality of the
specimens exposed to different concentrations, and thirdly we examined
histopathological alterations (degenerative processes ranging from inflammatory
responses to extreme vacuolation) and histochemical changes in the distribution
of carbohydrates and proteins that appeared at each employed concentration. The
degree of these alterations and the effects on survival were dependent upon the
SDS concentration. The above established modifications indicate that exposure to
SDS has a detrimental effect on oyster digestive gland, perturbing metabolic and
nutritional functions, what may have some influence on oyster survival.
PMID- 11005239
TI - Melanization stimulating factors in the integument of the Mugil cephalus and
Dicertranchus labrax.
AB - The pigment pattern expression resides in the chromatoblasts of the embryonic
skin. The differentiation of these chromatoblasts is influenced by specific local
factors such a melanization inhibiting factor (MIF) and a melanization
stimulating factor (MSF). We reveal the presence of these factors by means of a
series of experiments on the skin of the marine species of fish Dicertranchus
labrax and Mugil cephalus, each with different pigment pattern, the former having
a light skin and the latter a darker one. Media conditioned by exposure to dorsal
and/or ventral skin, stimulates the melanization of Xenopus laevis neural crest
cells throughout a 3 day assay period. Similarly conditioned culture media tested
on B16-F10 murine malignant melanocytes, revealed a considerable influence in
enzymatic activities: dopachrome tautomerase (DCT), tyrosine hydroxylase and dopa
oxidase. The use of media in a dose response basis suggests that the conditioned
media may contain both melanophore stimulating and inhibiting factors. The
results obtained may actually reflect the resultant activity of the two factors
present.
PMID- 11005240
TI - Molecular actions of nitric oxide in mesangial cells.
AB - Nitric oxide (NO) is a widely recognized mediator of physiological and
pathophysiological signal transmission. Its generation through L-arginine
metabolism is relevant in the mesangium of the kidney where NO is produced by
constitutive and inducible NO-synthase isoenzymes. Signaling is achieved through
target interactions via redox and additive chemistry. In mesangial cells (MC),
the outcome of these modifications promote on one side activation of soluble
guanylyl cyclase while on the other side cytotoxicity is elicited. These
contrasting situations are characterized by: 1) cGMP formation and signal
propagation towards myosin light chain kinase, the effector system that regulates
F-actin assembly, thereby affecting reversible relaxation/contraction of
mesangial cells; and 2) initiation of morphological and biochemical alterations
that are reminiscent of apoptosis such as chromatin condensation, p53 or Bax
accumulation as well as caspase-3 activation. Off note, NO formation with
concomitant initiation of apoptosis is efficiently antagonized by the
simultaneous presence of superoxide (O2-). We will recall the consequences that
stem from a diffusion controlled NO/O2- interaction thereby redirecting the
apoptotic initiating activity of either NO or O2- towards protection. The
crosstalk between cell destructive and protective signaling pathways, their
activation or inhibition under the modulatory influence of NO will be discussed.
Here we give examples of how NO elicits physiological and pathophysiological
signal transmission in rat MC.
PMID- 11005241
TI - Liver fibrosis, the hepatic stellate cell and tissue inhibitors of
metalloproteinases.
AB - Liver fibrosis occurs as a consequence of net accumulation of matrix proteins
(especially collagen types I and III) in response to liver injury. The
pathogenesis of liver fibrosis is underpinned by the activation of hepatic
stellate cells (HSC) to a myofibroblast like phenotype with a consequent increase
in their synthesis of matrix proteins such as interstitial collagens that
characterise fibrosis. In addition to this there is increasing evidence that
liver fibrosis is a dynamic pathologic process in which altered matrix
degradation may also play a major role. Extracellular degradation of matrix
proteins is regulated by matrix metalloproteinases (MMPS)- produced by HSC--which
in turn are regulated by several mechanisms which include regulation at the level
of the gene (transcription and proenzyme synthesis), cleavage of the proenzyme to
an active form and specific inhibition of activated forms by tissue inhibitors of
metalloproteinases (TIMPS). Insights gained into the molecular regulation of HSC
activation will lead to therapeutic approaches in treatment of hepatic fibrosis
in the future, and could lead to reduced morbidity and mortality in patients with
chronic liver injury.
PMID- 11005242
TI - Integrin activation by chemokines: relevance to inflammatory adhesion cascade
during T cell migration.
AB - The adhesive function of integrins is regulated through cytoplasmic signaling
induced by several stimuli, whose process is designated "inside-out signaling". A
large number of leukocytes are rapidly recruited to the sites of inflammation
where they form an essential component of the response to infection, injury,
autoimmune disorders, allergy, tumor invasion, atherosclerosis and so on. The
recruitment of leukocytes into tissue is regulated by a sequence of interactions
between the circulating leukocytes and the endothelial cells. Leukocyte integrins
play a pivotal role in leukocyte adhesion to endothelial cells. During the
process, the activation of integrins by various chemoattractants, especially
chemokines, is essential for integrin-mediated adhesion in which a signal
transduced to the leukocyte converts the functionally inactive integrin to an
active adhesive configuration. We have proposed that H-Ras-sensitive activation
of phosphoinositide 3 (PI 3)-kinase and subsequent profilin-mediated actin
polymerization, can be involved in chemokine-induced integrin-dependent adhesion
of T cells. The present review documents the relevance of cytoplasmic signaling
and cytoskeletal assembly to integrin-mediated adhesion induced by
chemoattractants including chemokines during inflammatory processes. In contrast,
various adhesion molecules are known to transduce extracellular information into
cytoplasm, which leads to T cell activation and cytokine production from the
cells, designated "outside-in signaling". Such a bi-directional "cross-talking"
among adhesion molecules and cytokines is most relevant to inflammatory processes
by augmenting immune cell migration from circulation into inflamed tissue such as
rheumatoid arthritis, tumor invasion, Behcet's disease and atherosclerosis.
PMID- 11005243
TI - Molecular genetic approaches to microtubule-associated protein function.
AB - Protein function in vivo can be studied by deleting (knock-out) the gene that
encodes it, and search for the consequences. This procedure involves different
technologies, including recombinant DNA procedures, cell biology methods and
histological and immunocytochemical analysis. In this work we have reviewed these
procedures when they have been applied to ascertain the function of several
microtubule-associated proteins. These proteins have been previously involved,
through in vitro experiments, in having a role in the microtubule stabilization.
Here, we will summarize the generation and characterization of different
microtubule-associated protein knock-out mice. Special attention will be paid to
MAP1B knock-out mice. Amongst the different MAPs knock-out mice these show the
strongest phenotype, the most likely for being MAP1B, the MAP that is expressed
earliest in neurogenesis. Molecular genetics could be considered as a valid and
useful procedure to truly establish the in vivo functions of a protein, although
it is necessary to be aware of possible artifacts such as the generation of some
kinds of RNA alternative splicing. To avoid this the best strategy to be used
must consider the deletion of the exon that contains the functional domains of
the protein.
PMID- 11005244
TI - Clinical applications of image cytometry to human tumour analysis.
AB - Image cytometry (ICM) is widely applied to the automated screening, the
detection, the diagnosis, the classification, the prognosis and the therapeutic
follow-up of different types of cancers (breast, bladder, cervix,...). This
review describes the analysis methods and the applications of nuclear image
analysis, the determination of DNA content and the analysis of morphometry and of
nuclear texture. DNA content analysis can contribute to a prognostic information
in addition to other prognostic factors for breast, renal and prostate cancers.
For ovarian cancer, aneuploidy seems to be related to prognosis. Bladder tumours
with DNA aneuploidy were frequently of high malignancy while ploidy was
significantly correlated to relapse risk. For digestive cancers, patients
presenting DNA diploid tumours show a better survival than patients with
aneuploid ones. Morphometry seems to be a more important criterion than other
conventional prognostic factors of invasive breast and digestive carcinomas. A
differential diagnosis between normal and neoplastic thyroids is more precise
when based on a quantitative evaluation of texture associated to morphometry.
Textural parameters permit the discrimination of two populations of patients
having a different prognosis and could thus be an aid for prognosis in prostatic
cancers. Morphonuclear parameters contribute to separate low and high grade
bladder carcinomas. Although ICM was frequently reported, results from the
reported examples were not always obvious. In conclusion, the measurements
obtained with ICM could be helpful for a decision in several cancers but could
not be a substitute for the classical approach of the pathologist.
PMID- 11005245
TI - Adoptive cellular immunotherapy: NK cells and bone marrow transplantation.
AB - Allogeneic bone marrow transplantation (BMT) has been increasingly used for the
treatment of both neoplastic and non-neoplastic disorders. However, serious
obstacles currently limit the efficacy and thus more extensive use of BMT. These
obstacles include: graft-versus-host disease (GVHD), relapse from the original
tumor, and susceptibility of patients to opportunistic infections due to the
immunosuppressive effects of the conditioning regimen. Overcoming these obstacles
is complicated by dual outcome of existing regimens; attempts to reduce GVHD by
depleting T cells from the graft, result in increased rates of tumor relapse and
failure of engraftment. On the other hand, efforts to increase graft-versus-tumor
(GVT) effects of the transplant also promote GVHD. In this review, the use of
natural killer (NK) cells to overcome some of these obstacles of allogeneic BMT
is evaluated. Adoptive immunotherapy using NK cells after allogeneic BMT has
several potential advantages. First, NK cells can promote hematopoiesis and
therefore engraftment by production of hematopoietic growth factors. Second, NK
cells have been shown to prevent the incidence and severity of GVHD. This has
been shown to be at least partially due to TGF-beta, an immunosuppressive
cytokine. Third, NK cells have been shown to augment numerous anti-tumor effects
in animals after BMT suggesting a vital role of NK cells in mediating GVT
effects. Finally, NK cells have been demonstrated to affect B cell recovery and
function in mice. Therefore, understanding the mechanisms of beneficial effects
of NK cells after BMT may lead to significant increases in the efficacy of this
procedure.
PMID- 11005246
TI - Cell proliferation and apoptosis in prostate cancer: significance in disease
progression and therapy.
AB - Recent biochemical and genetic studies have substantially increased our
understanding of death signal transduction pathways, making it clear however,
that apoptosis is not a single-lane, one-way street. Rather, multiple parallel
pathways have been identified. For instance, analysis of bcl-2, bax, p53, and
caspase knockout mice while establishing distinct roles for each of these
apoptotic players, they also provided valuable information for the design of
specific inhibitors of apoptosis. Thus blocking one pathway, as in caspase
knockout mice, what we observe is not a complete suppression of apoptosis but
rather a delay in apoptosis induction (Hakem et al., 1998; Kuida et al., 1998).
In view of nature's means of ensuring activation of a compensatory apoptotic
response, when one pathway fails in developing prostate cancer therapeutic
interventions, the challenge remains to further dissect individual apoptotic
pathways. Advances in our understanding of the integrated functions governing
prostate cell proliferation and cell death, clearly suggest that effective
prostate cancer therapies are not only molecularly targeted, but that are also
customized to take into account the delicate balance of opposing growth
influences in the ageing gland. In this review we discuss the evidence on the
significance of molecular deregulation of the key players of this growth
equilibrium, apoptosis and cell proliferation in prostate cancer progression, and
the clinical implications of changes in the apoptotic response in disease
detection and therapy.
PMID- 11005247
TI - Use of interphase cytogenetics in demonstrating specific chromosomal aberrations
in solid tumors--new insights in the pathogenesis of malignant melanoma and head
and neck squamous cell carcinoma.
AB - The detection of structural and numerical chromosomal aberrations is an important
part of the characterization of tumors and genetic diseases. The direct
demonstration of DNA sequences in interphase nuclei and metaphases by
fluorescence in situ hybridization (FISH) has been termed interphase
cytogenetics. It has been proven as a powerful technique to detect specific
aberrations in a wide variety of cell types, including paraffin-embedded tissue.
Nowadays a standard method in leukemia and lymphoma, interphase cytogenetics
contributes mainly to the diagnosis in these tumors and helps to classify soft
tissue tumors. Therefore FISH is mandatory for the choice of therapy in these
tumors. In contrast to the aforementioned, up to now, the value of FISH in solid
tumors is mostly limited to pure research and contributes in this way to our
understanding of tumor biology. But with the use of paraffin-embedded tissue and
the first results obtained, it seems very likely that a direct correlation
between histological classification and cytogenetic characteristics of solid
tumors can be achieved in the near future. This information might not only
provide insights into tumor biology, but could also contribute to a different
tumor classification, a sort of risk estimation, where we might predict the
possible biological behavior of solid tumors. This could greatly influence
further therapeutic decisions thus establishing the FISH technique as an
indisputable part in the diagnosis of solid tumors.
PMID- 11005248
TI - Gene therapy strategies for intracranial tumours: glioma and pituitary adenomas.
AB - Intracranial tumours such as brain gliomas and pituitary adenomas pose a
challenging area of research for the development of gene therapy strategies, both
from the point of view of the severity of the diseases, to the physiological
implication of gene delivery into the central nervous system and pituitary gland.
On the one hand, brain gliomas are very malignant tumours, with a life expectancy
of six months to a year at the most after the time of diagnosis, in spite of
advances in treatment modalities which involve chemotherapy, surgery and
radiotherapy. Gene therapy for these tumours is therefore a very attractive
therapeutic modality which due to the severity of the disease is already in
clinical trials. On the other hand, pituitary tumours are usually benign, and in
most cases, treatment is successful. Nevertheless, there are some instances,
especially with the macroadenomas and some invasive tumours in which treatment
fails. Gene therapy strategies for these adenomas therefore needs to progress
substantially in terms of safety, adverse side effects and physiological impact
on the normal pituitary gland before clinical implementation. In this paper, we
will review gene delivery systems both viral and non-viral and several
therapeutic strategies which could be implemented for the treatment of these
diseases. These include cytotoxic approaches both conditional and direct, immune
stimulatory strategies, anti-angiogenic strategies and approaches which harness
pro-apoptotic and tumour suppressor gene targets. We will also review the models
which are currently available in which these gene therapy strategies can be
tested experimentally. This new therapeutic modality holds enormous promise, but
we still need substantial improvements both from the delivery, efficacy and
safety stand points before it can become a clinical reality.
PMID- 11005249
TI - Gene therapy using herpes simplex virus-based vectors.
AB - Gene therapy involves the use of specific genes to treat human diseases and is
thus critically dependent on efficient gene delivery systems. Although a variety
of systems for such gene delivery are under development, HSV has unique
advantages in terms of its large genome size and for gene delivery in the nervous
system because of its ability to enter a latent state in neuronal cells.
Considerable progress has been made in the effective disablement of this virus
whilst retaining its ability to deliver genes and in producing long term
expression of the foreign gene. Although much remains to be achieved in the
further disablement of the virus and its testing in rodent and primate models of
human diseases, it is likely that these viruses may ultimately be of use in human
gene therapy procedures particularly for otherwise intractable neurological
diseases.
PMID- 11005250
TI - Localization of androgen and estrogen receptors in rat and primate tissues.
AB - There is now evidence that estrogens and androgens are exerting their effects in
different tissues throughout the body. In order to determine the sites of action
of these steroids, studies have been performed to identify at the cellular level
the localization of androgen receptor (AR) and the two estrogen receptor (ER)
subtypes, ERalpha and ERbeta, specially in the rat, monkey and human. In the
prostate, AR was observed in the secretory and stromal cells. In the testis,
Sertoli, Leydig and myoid cells were labelled. In the epididymis and seminal
vesicles, both epithelial and stromal cells contained AR. In the ovary, AR was
detected in granulosa and interstitial cells. In the uterus, epithelial, stromal
and muscle cells were all immunopositive for AR. In the central nervous system,
AR-containing neurons were found to be widely distributed throughout the brain.
In the mammary gland, epithelial cells in acini and ducts and stromal cells were
demonstrated to express AR. In the skin, AR was detected in keratinocytes,
sebaceous and sweat glands, and hair follicles. In addition, AR was also found in
anterior pituitary, thyroid, adrenal cortex, liver, kidney tubules, urinary
bladder, cardiac and striated muscle, and bone. The ER subtypes are in general
differentially expressed. While ERalpha has been predominantly found in anterior
pituitary, uterus, vagina, testis, liver and kidney, ERbeta is predominant in
thyroid, ovary, prostate, skin, bladder, lungs, gastro-intestinal tract,
cartilage and bone. In tissues which contain both receptor subtypes, such as
ovary, testis and various regions of the brain, a cell-specific localization for
each ER subtype has been generally observed. Altogether, the recent results on
the cellular localization of sex steroid receptors will certainly contribute to a
better understanding of the specific role of these steroids in different target
organs.
PMID- 11005251
TI - Identification and characterization of genes responsive to apoptosis: application
of DNA chip technology and mRNA differential display.
AB - Apoptosis (programmed cell death) is a genetically programmed active cell death
process for maintaining homeostasis under physiological conditions and for
responding to various stimuli. Many human diseases have been associated with
either increased apoptosis (such as AIDS and neurodegenerative disorders) or
decreased apoptosis (such as cancer and autoimmune disorders). In an attempt to
understand apoptosis signaling pathway and genes associated with apoptosis, we
established two cell model systems on which apoptosis is induced either by DNA
damaging agent, etoposide or by redox agent, 1,10-phenanthroline (OP). DNA chip
profiling or mRNA differential display (DD) was utilized to identify genes
responsive to apoptosis induced by these two agents. In etoposide model with chip
hybridization, we defined signaling pathways that mediate apoptosis in p53
dependent manner (through activation of p53 target genes such as Waf-1/p21, PCNA,
GPX, S100A2 and PTGF-beta) as well as in p53-independent manner (through
activation of ODC and TGF-beta receptor, among others). In OP model with DD
screening, we cloned and characterized two genes: glutathione synthetase,
encoding an enzyme involved in glutathione synthesis and Sensitive to Apoptosis
Gene (SAG), a novel evolutionarily conserved gene encoding a zinc RING finger
protein. Both genes appear to protect cells from apoptosis induced by redox
agents. Further characterization of SAG revealed that it is a growth essential
gene in yeast and belongs to a newly identified gene family that promotes protein
ubiquitination and degradation. Through this activity, SAG regulates cell cycle
progression and many other key biological processes. Thus, SAG could be a valid
drug target for anti-cancer and anti-inflammation therapies.
PMID- 11005252
TI - Considerations on the thalamostriatal system with some functional implications.
AB - The thalamostriatal projections are largely neglected in current reviews dealing
with basal ganglia function. In the past few years, however, several studies have
re-evaluated these projections and have postulated their implication in more
complex tasks within the basal ganglia organization. In this review, we try to
focus on the morphological and functional importance of this system in the basal
ganglia of the rat, cat and monkey. Special attention is paid to the thalamus as
an important place for interaction between the input and the output systems of
the basal ganglia through the thalamostriatal projections. Thus, we stress on the
overlapping thalamic territories between the thalamic projection of the output
nuclei of the basal ganglia and the thalamostriatal neurons. Our experimental
data support the existence of several thalamic feedback circuits within the basal
ganglia functional design. Finally, some considerations are provided upon the
functional significance of these thalamic feedback circuits in the overall
organization of the basal ganglia in health and disease.
PMID- 11005253
TI - Biological and clinical review of stromal tumors in the gastrointestinal tract.
AB - Submucosal tumors of the gastrointestinal tract (GI tract) mainly consist of
gastrointestinal mesenchymal tumors (GIMTs) that are distributed in the GI tract
from the esophagus through the rectum. GIMTs include myogenic tumors, neurogenic
tumors and gastrointestinal stromal tumors (GISTs). The term "GIST" is now
preferentially used for the tumors that express CD34 and KIT. GIMTs are composed
of spindle or epithelioid cells, and 20% to 30% show malignant behavior,
including peritoneal dissemination and hematogenous metastasis. KIT expression
and mutations in the c-kit gene are found only in GISTs, but not in myogenic or
neurogenic tumors. Mutation in the c-kit gene is associated with aggressive
features and poor prognosis, and malignant GISTs frequently have mutations in the
c-kit gene. The clinicopathological features of GISTs with or without c-kit
mutations are markedly different. Therefore, GIMTs may be divided into four major
categories based on histochemical and genetic data: myogenic tumors; neurogenic
tumors; GISTs with c-kit mutation; and GISTs without c-kit mutation. The origin
of GISTs is not fully understood. However, phenotypical resemblance to the
interstitial cells of Cajal (ICCs) and gain-of-function mutations in the c-kit
gene may suggest origin from ICCs and/or multipotential mesenchymal cells that
differentiate into ICCs.
PMID- 11005254
TI - Signaling pathways mediated by tumor necrosis factor alpha.
AB - Tumor necrosis factor alpha (TNFalpha) has been shown to trigger many signaling
pathways. Following oligomerization by TNFalpha, the receptors TNF-RI and TNF-RII
associate with adapter molecules via specific protein-protein interactions. The
subsequent recruitment of downstream molecules to the receptor complex enables
propagation of the TNFalpha signal. Two cellular responses to TNFalpha have been
well documented, the induction of cell death and the activation of gene
transcription for cell survival. TNFalpha-induced apoptosis involves the
activation of caspase cascades, which culminate in the cleavage of specific
cellular substrates to effect cell death. TNFalpha has also been implicated in
various caspase-independent cell death processes. Two transcription factors
activated by TNFalpha are nuclear factor kappaB (NFkappaB) and activating protein
1 (AP-1). Pathways that promote the activation of these transcription factors
involve signaling molecules such as kinases, phospholipases, and
sphingomyelinases. In addition to increased survival (anti-apoptotic) gene
expression, NFkappaB and AP-1 also induce the expression of genes involved in
inflammation, cell growth, and signal regulation. The past decade has witnessed
the identification of numerous signaling intermediates implicated in TNFalpha
cellular responses. This article reviews the molecular mechanisms of TNFalpha
signal transduction. In particular, pathways involved in cell death and
transcription factor activation are discussed.
PMID- 11005255
TI - Apolipoprotein E and Alzheimer disease: an update on genetic and functional
analyses.
AB - Exceptional advances have been made in understanding the genetics of how common
polymorphisms of the apolipoprotein E gene influence the risk and age of onset of
Alzheimer disease (AD). The major genetic susceptibility locus for the common
forms of AD, there are 3 common alleles, designated epsilon2, epsilon3, and
epsilon4. The inheritance of each dose of APOE4 increases the risk of disease and
decreases the age of onset; conversely, the APOE2 allele appears to be
protective, by lowering the risk of disease and increasing the age of onset.
Testing for the APOE4 allele can be a clinically useful tool in the early
diagnosis of cognitively impaired patients suspected of having AD. The APOE4
allele also negatively influences functional recovery following a variety of
brain insults. What remains in the study of apolipoprotein E is an explanation of
how minor changes in a protein can produce such striking differences in risk and
age of onset. In vitro and animal model studies strongly suggest that brain
apolipoprotein E is a multifunctional molecule, with potential roles in amyloid
deposition and clearance, microtubule stability, intracellular signaling, immune
modulation, glucose metabolism, oxidative stress, and other cellular processes.
While the relevance of these proposed functions to the etiology of AD remains a
mystery, these and other hypotheses will be tested as the field of apoE
neurobiology grows, adding relevant new data to the functions of apoE in health
and in the pathogenic mechanisms leading to AD.
PMID- 11005256
TI - Loss of neurofibromin is associated with activation of RAS/MAPK and PI3-K/AKT
signaling in a neurofibromatosis 1 astrocytoma.
AB - Neurofibromatosis 1 (NF1) is a common autosomal dominant cancer predisposition
syndrome, in which 15% to 20% of affected individuals develop astrocytomas.
Neurofibromin, the protein product of the NF1 gene, functions as a tumor
suppressor, largely by inhibiting Ras activity. While loss of neurofibromin has
been implicated in the molecular pathogenesis of other NF1-associated tumors,
there is no formal evidence demonstrating loss of neurofibromin function in NF1
associated astrocytomas. In this report, we describe an NF1 patient from whom
both astrocytoma tumor tissue as well as corresponding non-neoplastic white
matter were available for analysis. Loss of neurofibromin expression was observed
in the tumor and was associated with elevated levels of Ras-GTP. However,
elevated Ras-GTP levels were not the result of oncogenic Ras mutations, altered
p120-GAP function, growth factor receptor activation, or abnormal p53, Rb, or p16
expression. Furthermore, increased Raf-MAPK and PI3-K/Akt activity was detected
in the NF1 astrocytoma compared with the corresponding normal white matter. These
results support a role for neurofibromin as the critical GAP in the molecular
pathogenesis of NF1 astrocytomas.
PMID- 11005257
TI - Cerebral beta amyloid angiopathy is a risk factor for cerebral ischemic
infarction. A case control study in human brain biopsies.
AB - Cerebral amyloid angiopathy (CAA) is conspicuous for its association with
Alzheimer disease (AD) and as a cause of lobar hemorrhages in the elderly, but
its role in cerebral infarction is less clear. There is evidence that CAA may
also be a risk factor for ischemic infarction in AD. To further investigate CAA
as a risk factor for infarction, we studied 108 cases of recent cerebral or
cerebellar infarction diagnosed in tissue samples obtained from surgical
material. There were 69 males and 39 females with a mean age of 52 yr (range 1
86). The majority of biopsies were obtained from the frontal and parietal lobes.
Radiological studies demonstrated a lesion confined to a vascular distribution in
12 of the 17 (71%) cases examined. Microscopic sections stained with hematoxylin
and eosin revealed complete, organizing infarction in 107 cases with areas of
coagulative necrosis, anoxic-ischemic neuronal injury, inflammation, macrophages,
vascular proliferation, gliosis, and swollen axons. One case showed an incomplete
infarct. Most cases also exhibited a minor hemorrhagic component with hemosiderin
and hematoidin pigments. CAA, defined as amyloid deposition in the walls of
leptomeningeal and parenchymal arteries, was found by immunohistochemical stains
for beta amyloid in 14 (13%) cases of complete cerebral infarct. Cortical beta
amyloid plaques were found by immunohistochemistry in 19 (17%) cases. Cerebral or
cerebellar tissues containing cortex and leptomeninges obtained from 136 patients
with a mean age of 52 yr (range 1-85) during surgical procedures for diagnosis of
primary or metastatic neoplasms and demyelinating lesions were used as age
matched controls. In this control group, CAA was found in 5 (3.7%) and beta
amyloid plaques in 19 (14%). The results indicate that CAA, but not beta amyloid
plaque formation, is significantly more common in patients with ischemic cerebral
infarction than in age-matched controls with nonvascular lesions (odds ratio 3.8;
95% confidence interval 1.3-10.9; p < 0.01). Our results indicate that CAA is a
risk factor for ischemic cerebral infarction in the population studied.
PMID- 11005258
TI - Enhanced CD9 expression in the mouse and human brains infected with transmissible
spongiform encephalopathies.
AB - A tetraspan protein CD9, normally expressed in the myelin sheath of the central
and peripheral nervous system, was identified to be up-regulated in mouse brains
infected with transmissible spongiform encephalopathy (TSE), by mRNA differential
display screening. To elucidate its role in the neurodegeneration process
observed in TSE, CD9 expression was examined in the murine disease model and in
the human disease materials. Up-regulation of CD9 gene expression in the TSE
infected mouse brains was detected as early as a preclinical stage, when abnormal
prion protein deposition and vacuolation were obviously manifested in the
internal capsule and thalamus. In contrast, other myelin protein genes showed a
reverse pattern of CD9 gene expression. Enhanced CD9 expression was
immunohistochemically detected in the astrocytes of such pathological regions. In
human specimens of TSE, enhanced CD9 immunoreactivity was observed in the
astrocytes and some oligodendrocytes in the brains, but no relevant alteration in
CD9 immunoreactivity was observed in the other organs or tissues. Positive CD9
immunoreactivity in astrocytes was also manifest in other neurological disorders
in a less prominent manner. The findings indicate that up-regulated CD9 plays a
role in glial cells in pathological conditions, especially in such a devastating
condition as TSE.
PMID- 11005259
TI - Disulfiram produces a non-carbon disulfide-dependent schwannopathy in the rat.
AB - Disulfiram is a dithiocarbamate drug used for alcohol aversion therapy that
produces a distal sensorimotor peripheral neuropathy in certain individuals.
Because carbon disulfide, a disulfiram metabolite, produces a peripheral
neuropathy clinically similar to disulfiram, it has been postulated that
disulfiram neuropathy results from CS2 release in vivo. The current study
evaluated the morphological changes produced by disulfiram and the contribution
of CS2-mediated protein cross-linking to disulfiram-induced neuropathy. Male
Sprague-Dawley rats were administered 1% w/w disulfiram in their feed for 2, 4,
5, or 7 wk, and erythrocyte spectrin, hemoglobin, and neurofilament preparations
were isolated and the extent of cross-linking assessed by SDS-PAGE, RP-HPLC, and
Western blotting, respectively. Spinal cord and peripheral nerve sections were
obtained from separate treated animals and assessed by light and electron
microscopy. Significant protein cross-linking was only detected in neurofilament
preparations obtained after 7 wk of exposure. Morphological changes were observed
after 4 wk exposure and consisted of vacuoles within the Schwann cell cytoplasm
and segmental demyelination. No neurofilamentous axonal swellings were detected
and no significant changes were observed in the CNS. Because disulfiram
neuropathy lacks both the morphological changes and intermolecular cross-linking
characteristic of CS2, we conclude that disulfiram neuropathy is not mediated by
the axonal toxicant CS2; instead, disulfiram appears to be a primary Schwann cell
toxicant. Recognition of a diethylcarbamoyl adduct on globin and axonal proteins
presents a novel putative neurotoxic mechanism for disulfiram.
PMID- 11005260
TI - Nitric oxide synthase activity and expression in experimental diabetic
neuropathy.
AB - The changes of nitric oxide synthase (NOS) activity and expression in
experimental diabetic neuropathy have not been examined. Increases in ganglia NOS
might be similar to those that follow axotomy, whereas declines in endothelial
NOS (eNOS) and immunological NOS (iNOS) might explain dysfunction of microvessels
or macrophages. In this work, we studied NOS activity in lumbar dorsal root
ganglia (DRG) of rats with both short- and long-term experimental streptozotocin
induced diabetes and correlated it with expression of each of the 3 NOS isoforms.
NOS enzymatic activity in DRG increased after 12 months of diabetes. This
increase, however, was not accompanied by an increase in neuronal NOS
immunohistochemistry or mRNA. Immunohistochemical and RT-PCR studies did not
identify changes of eNOS expression in 12-month sciatic nerves or DRG from
diabetics. Two-month diabetic DRG had increased eNOS mRNA and there was novel
eNOS labeling of capsular DRG and perineurial cells. iNOS mRNA levels were lower
in diabetics at both time points in peripheral nerves but were unchanged in DRG.
Diabetic ganglia showed an increase in NOS activity not explained by novel NOS
isoform synthesis. The increases may compensate for NO "quenching" by endproducts
of glycosylation. Declines in iNOS may indicate impaired macrophage function.
PMID- 11005261
TI - Further evidence for the involvement of epidermal growth factor in the signaling
pathway of vitamin B12 (cobalamin) in the rat central nervous system.
AB - In order to get further evidence for a mandatory involvement of epidermal growth
factor (EGF) in the neutrophic action of vitamin B12 (cobalamin (Cbl)) in the
central nervous system (CNS) of the rat, we observed the effects of repeated
intracerebroventricular (ICV) microinjections of EGF in rats made Cbl-deficient
through total gastrectomy. Morphometric analysis demonstrated a significant
reduction in both intramyelinic and interstitial edema in the white matter of the
spinal cord (SC) of totally gastrectomized (TGX) rats after treatment.
Intramyelinic and interstitial edema are characteristic of Cbl-deficient central
neuropathy in the rat. Similar lesions were also present in SC white matter of
rats treated with repeated ICV microinjections of specific anti-EGF antibodies
without any modification in their Cbl status. These results, together with those
of a previous study showing the cessation of EGF synthesis in the CNS of TGX
rats, demonstrate that: a) EGF is necessarily involved in the signaling pathway
of Cbl in the rat CNS; and b) the lack of a neurotrophic growth factor EGF, and
not the mere withdrawal of Cbl, causes or at least contributes to
neurodegenerative Cbl-deficient central neuropathy.
PMID- 11005262
TI - Comparative genomic hybridization in pineal germ cell tumors.
AB - Fifteen primary pineal germ cell tumors (8 germinomas, 4 mixed teratomas
germinomas, 2 immature teratomas, and 1 yolk sac tumor) and 2 recurrences of the
yolk sac tumor were studied by comparative genomic hybridization (CGH). An
average of 1.8 chromosomal changes per germinoma (0.5 gains vs 1.3 losses), 5.5
per mixed teratoma-germinoma (3.0 gains vs 2.5 losses), 3.5 per immature teratoma
(2.0 gains vs 1.5 losses), and 2.0 in the yolk sac tumor (2 gains vs 0 losses)
were found; the first recurrence showed 7 (4 gains vs 3 losses), the second 13
imbalances (8 gains vs 5 losses). The most frequent imbalances were gains on 12p
(40%), 8q (27%), and 1q (20%) as well as losses on 13q (47%), 18q (33%), 9q and
11q (20% each). Among germinomas, the most common chromosomal changes were -13q
and -18q (38% each), in mixed teratomas-germinomas +8q (100%), +12p (75%), -13q
(75%) and -9q (50%). Seven high-level gains were identified: 5 in mixed teratomas
germinomas (+8q: 3 cases, + 12p: 2 cases), 1 each in a germinoma (+2p) and an
immature teratoma (+12p). Minimal common regions of over- and underrepresentation
were found on +8q11.22-21.1, +12p11.1-12.1, -9q32-qter, -11q23.2-qter, -13q32
qter and -18q22-qter. Our findings suggest, that imbalances in cerebral germ cell
tumors affect the same chromosomes as among their extracerebral counterparts,
albeit in a considerably lower frequency among cerebral germinomas where +12p
does not seem to play a major role.
PMID- 11005263
TI - Tracing cranial nerve pathways (glossopharyngeal, vagus, and hypoglossal) in SIDS
and control infants: a DiI study.
AB - It has been proposed that Sudden Infant Death Syndrome (SIDS) might occur as a
consequence of a developmental deficit associated with the cardiorespiratory and
arousal control centers located within the brainstem. In this study 1.1'
dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate (DiI) was used to
investigate the trajectories of the glossopharyngeal and vagus nerves which carry
essential afferent and efferent fiber tracts associated with cardiac and
respiratory control and of the hypoglossal nerve which innervates the tongue, in
SIDS (n = 14) and control (n = 7) infants. The postnatal development of the
trajectories of these nerves was examined in non-SIDS brains and comparisons were
then made with age-matched SIDS brains. The mean profile area of hypoglossal and
dorsal motor neurons were also assessed. In controls, no major alterations were
observed in the trajectories of axon bundles with increasing age (7 wk to 2 yr)
in each of the nerves investigated although axon bundles appeared to increase in
thickness with age. In SIDS cases (2 wk to 44 wk), the trajectories of the
cranial nerves were not different from those seen in age-matched control cases.
The mean profile area of hypoglossal and dorsal motor neurons was not
significantly different between control and SIDS infants. We conclude that the
DiI tracing technique can be used successfully to trace the pathways of cranial
nerves in human infant fixed-tissue. Furthermore, if functional differences exist
between SIDS and non-SIDS brains in the control of respiration, circulation, or
arousal they do not appear to be related to markedly reduced or aberrant
projections of the glossopharyngeal, vagus, or hypoglossal nerves.
PMID- 11005264
TI - Immunohistochemical and biochemical studies demonstrate a distinct profile of
alpha-synuclein permutations in multiple system atrophy.
AB - Although alpha-synuclein (alpha-syn) has been implicated as a major component of
the abnormal filaments that form glial cytoplasmic inclusions (GCIs) in multiple
system atrophy (MSA), it is uncertain if GCIs are homogenous and contain full
length alpha-syn. Since this has implications for hypotheses about the
pathogenesis of GCIs, we used a novel panel of antibodies to defined regions
throughout alpha-syn in immunohistochemical epitope mapping studies of GCIs in
MSA brains. Although the immunostaining profile of GCIs with these antibodies was
similar for all MSA brains, there were significant differences in the
immunoreactivity of the alpha-syn epitopes detected in GCIs. Notably, carboxy
terminal alpha-syn epitopes were immunodominant in GCIs, but the entire panel of
antibodies immunostained cortical Lewy bodies (LBs) in dementia with LBs brain
with similar intensity. While the distribution of alpha-syn labeled GCIs
paralleled that previously reported using silver stains, antibodies to carboxy
terminal alpha-syn epitopes revealed a previously undescribed burden of GCIs in
the MSA hippocampal formation. Finally, Western blots demonstrated detergent
insoluble monomeric and high-molecular weight alpha-syn species in GCI rich MSA
cerebellar white matter. Collectively, these data indicate that alpha-syn is a
prominent component of GCIs in MSA, and that GCIs and LBs may result from cell
type specific conformational or post-translational permutations in alpha-syn.
PMID- 11005265
TI - Evidence for a positive correlation between serum cortisol levels and IL-1beta
production by peripheral mononuclear cells in anorexia nervosa.
AB - A hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been
reported in anorexia nervosa (AN), together with some immunological
abnormalities, involving citokine - and particularly Tumor Necrosis-Factor-alpha
(TNF-alpha) - production by polymorphonuclear cells. The ability of pro
inflammatory cytokines to activate the HPA axis is well known; however, there are
no data demonstrating an interdependence between immunological and endocrine
response in AN. To investigate the presence of a correlation between immune
response and pituitary-adrenal function, plasma ACTH and serum cortisol
concentrations were measured in 13 AN patients and in the same number of
controls. TNF-alpha and interleukin (IL)-1beta production by ex-vivo unstimulated
and LPS-stimulated peripheral mononuclear cells was also assessed. Circulating
cortisol concentrations were higher (p<0.01) in AN (156.7 +/- 45.1 microg/l, mean
+/- SD) than in controls (105.9 +/- 25.7 microg/l). Unstimulated IL-1beta release
in supernatants of mononuclear cell cultures was slightly but not significantly
higher in AN than in controls, while TNF-alpha release was similar in the two
groups. A positive correlation was found between IL-1beta concentrations in
unstimulated culture supranatants and serum cortisol levels in AN (r=0.782,
p=0.002), while in normal subjects there was a trend toward a negative
correlation; a slight positive correlation, while not significant, between IL
1beta and plasma ACTH, as well as between TNF-alpha and serum cortisol was also
found in AN. These data suggest that the normal relationship between pro
inflammatory cytokines release, particularly IL-1beta, and cortisol secretion is
deranged in AN.
PMID- 11005266
TI - A randomized cross-over study comparing cabergoline and quinagolide in the
treatment of hyperprolactinemic patients.
AB - Quinagolide (QUI) and cabergoline (CAB) are dopamine agonists recently introduced
for the treatment of hyperprolactinemia. In the present study, these drugs have
been compared in terms of effectiveness and tolerability. Twenty patients (18
females and 2 males) with hyperprolactinemia (8 with microprolactinomas, 6 with
idiopathic hyperprolactinemia and 6 with empty sella turcica syndrome) were
treated with oral QUI (75 microg once daily) and CAB (0,5 mg twice weekly), in a
randomized cross-over trial with placebo between both drugs. Each drug was
administered for 12 weeks, separated by other 12 weeks with placebo. PRL levels
decreased with both drugs at 2 or 4 weeks of starting the treatment, without
differences between both drugs at weeks 4, 8 and 12. At week 12, normal PRL
levels (<20 ng/ml) were attained in 90% patients with CAB and only in 75%
patients with QUI (p<0.05). After discontinuation of treatment, significant
increase in serum PRL was higher after QUI withdrawal than after CAB. Clinical
efficacy of both treatments was similar in terms of improvement amenorrhea,
oligomenorrhea, galactorrhea, and impotence. All patients completed both cycles
of treatment, and the most frequent side-effects were nausea, headache and
dizziness, without significant differences between CAB (30%) and QUI (55%). Our
study indicates that, at the doses employed here, CAB showed a high percentage of
patients with normal PRL at the end of treatment and long-lasting efficacy in the
levels of PRL. Clinical response and side-effects were similar in both drugs.
PMID- 11005267
TI - Urinary cortisol to cortisone metabolites in hypertensive obese children.
AB - Childhood obesity is accompanied by a variety of cardiovascular risk factors
(hypertension, insulin resistance, dyslipidaemia) which tend to aggregate
(syndrome X). 11beta-hydroxysteroid dehydrogenase (11beta-HSD) is supposed to
play a role in the pathogenesis of hypertension and the development of syndrome
X. There are two isoforms of 11beta-HSD. 11beta-HSD-2 is responsible for the
inactivation of cortisol to inactive cortisone. In the case of impaired enzyme
activity the ratio of urinary tetrahydrocortisol (THF)+ its isomer
allotetrahydrocortisol (5alpha-THF)/tetrahydrocortisone (THE) is elevated. 11beta
HSD-1 is an oxo-reductase, which type catalyses the conversion of cortisone to
cortisol. The aim of the present study was to investigate if there was any
alteration in the urinary cortisol metabolites reflecting 11beta-HSD activity in
hypertensive obese children (no.=15) as compared to normotensive obese (no.=11)
and normotensive non-obese children (no.=15). We found an increased excretion of
cortisol metabolites in hypertensive obese children compared to obese and normal
weight children having normal blood pressure. The ratio of THF+5alpha(THF/THE
had a significant correlation with systolic blood pressure. On the basis of our
study the ratio of THF+5alpha-THF/ THE reflecting on altered enzyme activity
seems to be an independent factor influencing especially systolic blood pressure
in hypertensive obese children.
PMID- 11005268
TI - Sexual dimorphism in the hypothalamo-pituitary-adrenal (HPA) axis and TNFalpha
responses to phospholipase A2-related neurotoxin (from crotalus durissus
terrifcus) challenge.
AB - Neuroendocrine-immune interactions are vital for the individual's survival in
certain physiopathological conditions such as sepsis and tissular injury. It is
known that several snake venoms (SV) are potent neurotoxic compounds and that
their main component is a specific phospholipase type 2 (PLA2). It has been
recently described that the venom from crotalus durissus terrificus (SV)
possesses a cytotoxic effect in different in vitro and in vivo animal models. In
the present study we investigated whether SV is able to stimulate both TNFalpha
and neuroendocrine functions in a sexual dimorphic fashion. For this purpose the
modulatory role of endogenous sex steroids during neurotoxemia was evaluated. Our
results indicate that SV (25 microg/animal) stimulates the hypothalamo-pituitary
adrenal axis and TNFalpha secretion when administered (ip) to adult male mice,
such responses were characterized by a time-related enhance in plasma glucose,
ACTH, corticosterone and TNFalpha levels. SV-stimulated glycemia,
corticosteronemia and adrenal glucocorticoid were sexually dimorphic. Twenty-day
gonadectomized mice showed a similar sexual dimorphism to that found in intact
animals, however, they additionally showed a sexual dimorphic pattern in cytokine
release in plasma 30 min post-SV. Estradiol (E2) treatment, in gonadectomized
mice, abolished some characteristics of the sexual dimorphism, such as
hyperglycemia, hypercorticosteronemia and hypercytokinemia. Finally, in vitro
experiments indicate that: a) gonadectomy increased spontaneous and SV-stimulated
cytokine output by incubated peripheral mononuclear cells (PMNC), regardless of
the sex; and b) despite E2 treatment, in gonadectomized, did not modify the
pattern of basal and SV-elicited TNFalpha secretion induced by orchidectomy,
fully reversed the enhance in basal and SV-stimulated cytokine release found
after ovariectomy alone. Our results further indicate that neurotoxemia, due to
SV challenge, induces several symptoms common to those of inflammatory stress;
they also strongly support that both gender and endogenous sex steroids are
responsible for neuroendocrine-immunological sexual dimorphism.
PMID- 11005269
TI - Intersubject responsiveness of high-affinity growth hormone (GH)-binding protein
(GHBP) to long-term GH replacement therapy.
AB - In adult growth hormone deficiency (GHD) syndrome responsiveness to GH
replacement therapy is reported to vary considerably. The underlying mechanisms,
however, are not well understood. The aim of this study was to investigate which
baseline variables determine the reported variable intersubject responsiveness of
high-affinity GH-binding protein (GHBP) to GH replacement therapy. In the setting
of a double blind study over 12 months with placebo control over the first 6
months, we analyzed the interrelationship between a number of baseline variables,
which vary considerably amongst subjects, and the GHBP response to GH replacement
in 31 GHD adults (21 males and 10 females). The following variables were
investigated: age, gender, duration of GHD, body composition, serum levels of
high-affinity GHBP, insulin-like growth factor-1 (IGF-1), and IGF-binding protein
3 (IGFBP-3). The results showed that in the 6 months treated group of 16 patients
(11 males, 5 females), serum IGF-1 increased from 87 ng/ml (range: 26 to 173) to
250 (range: 62 to 467) (p<0.01) and GHBP increased from 1,302 pmol/l (range: 845
to 1,m960) to 1418 (range: 941 to 2,025) (p=0.04). Both parameters showed a
significant time effect (within-subjects) (p<0.001). In the 12 months treated
group of 15 patients (10 males, 5 females), serum IGF-1 increased from 92 ng/ml
(range: 20 to 180) to 272 (range: 45 to 491) (p<0.01), whereas GHBP did not show
a significant change: from 1,186 pmol/l (range: 660 to 1,690) to 1,252 (range:
580 to 1,890) (p=0.87). Also no significant time effect (within-subjects) was
observed for GHBP (p=0.06). Step-wise multiple regression analyses revealed that
during the 6 months placebo period baseline GHBP explained 83% of the variance in
post-placebo GHBP, whereas the variance in post-treatment GHBP could be
accurately predicted (adjusted R2=0.93) from baseline GHBP and body fat mass,
irrespective of the duration of GH treatment. No other baseline variables
contributed independently to the GHBP response, with the exception of IGFBP-3,
which showed a small, but significant contribution in females, but not in males.
These findings indicate that the variable intersubject responsiveness of GHBP to
GH replacement therapy is mainly due to differences in baseline body fat mass
amongst adult GHD patients, and that in female patients a relatively low baseline
IGFBP-3 contributes to a rise in serum GHBP after GH treatment. The clinical
relevance of measuring GHBP in adult GHD patients is limited to the first
screening step to diagnose GHD, because long-term GH therapy tends to restore
serum GHBP to pretreatment levels.
PMID- 11005270
TI - Does kidney transplantation normalise cortisol metabolism in apparent
mineralocorticoid excess syndrome?
AB - The syndrome of apparent mineralocorticoid syndrome (AME) results from defective
11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2). This enzyme is co-expressed
with the mineralocorticoid receptor (MR) in the kidney and converts cortisol to
its inactive metabolite cortisone. Its deficiency allows the unmetabolized
cortisol to bind to the MR inducing sodium retention, suppression of PRA and
hypertension. Thus, the syndrome is a disorder of the kidney. We present here the
first patient affected by AME cured by kidney transplantation. Formerly, she was
considered to have a mild form of the syndrome (Type II), but progressively she
developed renal failure which required dialysis and subsequent kidney
transplantation. To test the ability of the transplanted kidney to normalise the
patient's cortisol metabolism, we gave, in two different experiments, 25 and 50
mg/day of cortisone acetate or 15 and 30 mg/day of cortisol after inhibition of
the endogenous cortisol by synthetic glucocorticoid (methylprednisolone and
dexamethasone). The AME diagnostic urinary steroid ratios
tetrahydrocortisol+5alphatetrahydrocortisol/tetrahydrocortisone and
cortisol/cortisone were measured by gas chromatography/mass spectrometry.
Transplantation resulted in lowering blood pressure and in normalization of serum
K and PRA. After administration of a physiological dose of cortisol (15 mg/day),
the urinary free cortisol/cortisone ratio was corrected (in contrast to the A
ring reduced metabolites ratio), confirming that the new kidney had functional
11beta-HSD2. This ratio was abnormally high when the supra-physiological dose of
cortisol 30 mg/day was given. After cortisone administration, the
tetrahydrocortisol+5alphatetrahydrocortisol/tetrahydrocortisone ratio resulted
normalised with both physiological and supra-physiological doses, confirming that
the hepatic reductase activity is not affected. As expected, the urinary free
cortisol/cortisone ratio was normal with physiological, but increased after supra
physiological doses of cortisone. The described case indicates a normalisation of
cortisol metabolism after kidney transplantation in AME patient and confirms the
supposed pathophysiology of the syndrome. Moreover, it suggests a new therapeutic
strategy in particularly vulnerable cohorts of patients inadequately responsive
to drug therapy or with kidney failure.
PMID- 11005271
TI - Cabergoline modulation of alpha-subunits and FSH secretion in a gonadotroph
adenoma.
AB - Most non-functioning pituitary adenomas respond poorly to medical therapy. We
describe the case of a 62-year-old man who presented with clinical features of an
invasive macroadenoma. Baseline hormonal evaluation revealed increased FSH and
alpha-subunit (alpha-SU) levels. Transsphenoidal exeresis followed by
radiotherapy (RT) was performed. Almost all neoplastic cells were intensely
immunoreactive for alpha-SU. On PCR analysis, specific amplification products
were observed for somatostatin 2, 3 and 5 receptors as well as for both short and
long isoforms of the dopamine D2 receptor. In vitro, alpha-SU and FSH were
released into the medium by adenoma cells and increased after TRH stimulation.
After surgery, alpha-SU and FSH levels were still elevated. Short-term slow
release lanreotide treatment did not modify either alpha-SU or FSH levels.
Cabergoline was started and a fast and long-lasting decrease in alpha-SU and, to
a lesser extent, in FSH was observed. The tumor remnant was unmodified on
magnetic resonance imaging 3 years after surgery and RT. This case report shows
that the in vitro expression of somatostatin receptors may not be directly
associated to the in vivo response of alpha-SU and FSH to lanreotide, probably
because of a functional uncoupling of the receptors. Cabergoline should be
considered as an effective therapy for hormonal, and perhaps proliferative,
control of gonadotroph adenoma remnants before the effects of RT are fully
effective.
PMID- 11005272
TI - Extremely high levels of estradiol and testosterone in a case of polycystic
ovarian syndrome. Hormone and clinical similarities with the phenotype of the
alpha estrogen receptor null mice.
AB - A 19-year-old nulliparous hirsute woman was evaluated for the very high serum
levels of testosterone (T) and estradiol (E2) measured in an outside laboratory.
Menarche had occurred at 11 years and was followed by regular menses. We
confirmed the high levels of T (9-16 ng/ml, nv 0.2-0.8) and E2 (>1,000 pg/ml, nv
30-120). LH and FSH were consistently high (73-118 mU/l and 18-29 mU/l,
respectively; LH/FSH ratio=4.1-4.7) and responsive to iv GnRH (LH baseline=118
mU/I, 30 min=290; FSH baseline=25 mU/l, 30 min=46). The unstimulated values
contrasted with those (LH=12, FSH=8 mU/I) measured in the outside laboratory,
suggesting antigenically anomalous gonadotropins. 17-OH-progesterone was normal
(0.5 ng/ml). After 1 mg dexamethasone, serum cortisol was normally suppressed (24
->0.4 microg/dl), T declined minimally (9-->8.6 ng/ml) and E2 remained high
(>1,000 pg/ml). An exploratory laparotomy was performed, and two enlarged ovaries
with multiple cysts as in a typical polycystic ovarian syndrome (PCOS) were seen.
Before the wedge resection of the ovaries, hormones were assayed in the ovary
veins (right ovary: T=30 ng/ml, Pg=17 ng/ml, E2=>5,000 pg/ml; left: T=14 ng/ml,
Pg=14 ng/ml, E2=>5,000 pg/ml). Histologically, the follicle cysts showed
luteinization of the theca interna; there was no evidence for ovary tumor in
either ovary. After 21 days of 35 microg ethynyl-E2+2 mg cyproterone acetate
(CA), E2=3,000 pg/ml, T=1.4 ng/ml, LH=10.5 mU/l and FSH=4.1 mU/I. After three
cycles of the said therapy (but with 50 mg CA in the first 10 days of each
cycle), E2 was 1,600 pg/ml, T 1.7 ng/ml, LH 7.1 and FSH 4.6 mU/I. Based on
similarities with the phenotype of the alpha estrogen receptor knockout female
mice (alphaERKO), one possible explanation for the puzzling clinical and
biochemical picture of our patient is resistance of (alphaER to estrogens. This
is the first case of PCOS with extremely high E2 and T. Thus, the differential
diagnosis of high levels of E2 +/- T should include PCOS.
PMID- 11005273
TI - The use of recombinant human TSH in a patient with metastatic follicular
carcinoma and insufficient endogenous TSH production.
AB - We present a case of a patient suffering from metastatic differentiated thyroid
carcinoma (DTC) and insufficient endogenous TSH production suspicious of
secondary hypothyroidism. The use of recombinant human TSH (rhTSH) enabled us to
administer a therapeutic activity of radioactive iodine (RAI) under maximal TSH
stimulation, achieving a marked decrease in thyroglobulin accompanied by a
clinical improvement.
PMID- 11005274
TI - Adrenal bilateral incidentaloma by reactivated histoplasmosis.
AB - We report a case of bilateral adrenal incidentaloma caused by the capsulatum
variety of Histoplasma capsulatum diagnosed in a 74 years old man born in and a
life time resident of Treviso, Italy, with the exception of two years spent in
Pakistan (1964-1966) as a well-driller. The patient was hospitalized in 1995 for
alcoholic chronic hepatitis, chronic Helicobacter pylori gastritis and post
infarction ischemic cardiomyopathy. Abdominal ultrasound incidentally showed
bilateral adrenal masses (the right one 6.3 cm in diameter) confirmed by computed
tomography, with adrenal function within normal limits. After three months, the
patient was again hospitalized due to evening fever, asthenia, anorexia, weight
loss and occasional hyperhidrosis. Abdominal ultrasound showed an increase of the
right adrenal lesion with normal adrenal function. Ultrasound-guided fine needle
aspiration did not prove useful for diagnosis. Accordingly, a laparotomy with
bilateral biopsy was performed; histology showed the presence of numerous tissue
form cells of H. capsulatum variety capsulatum. Serum anti-H. capsulatum
antibodies were negative. Since March, 1996, the patient was given itraconazole
and his symptoms quickly regressed but the computed tomography findings, however,
have not changed and the patient has adrenal hypofunction that is being treated
with cortisone acetate.
PMID- 11005275
TI - Reflections on growth hormone.
PMID- 11005277
TI - Hyperprolactinemia preceding Cushing's disease.
PMID- 11005276
TI - The metabolic effects of cyclosporin and tacrolimus.
AB - The introduction of cyclosporin and, more recently, tacrolimus in the
immunosuppression of transplanted patients has lead to prolonged graft survival
and increased patients' life expectancy. It has been therefore possible to
evaluate the effects of long-term treatment with these drugs and metabolic
alterations in patients on cyclosporin or tacrolimus have been reported by
several authors. In particular, the use of these drugs is associated with
abnormalities of glucose and lipid metabolism. Post-transplant diabetes is more
common with tacrolimus, probably due to more marked effects on the pancreatic
beta-cells, whereas increased levels of cholesterol and triglycerides are more
frequently associated with cyclosporin treatment, even though, in this latter
case, steroid treatment seems to play a major role. Comparison and intervention
studies must be planned to evaluate the best therapeutical approaches to control
these abnormalities and to assess the possibility to further increase graft and
patient survival by appropriate treatment of diabetes and hyperlipidemia.
PMID- 11005278
TI - Evolutionary developmental biology and the problem of variation.
AB - One of the oldest problems in evolutionary biology remains largely unsolved.
Which mutations generate evolutionarily relevant phenotypic variation? What kinds
of molecular changes do they entail? What are the phenotypic magnitudes,
frequencies of origin, and pleiotropic effects of such mutations? How is the
genome constructed to allow the observed abundance of phenotypic diversity?
Historically, the neo-Darwinian synthesizers stressed the predominance of
micromutations in evolution, whereas others noted the similarities between some
dramatic mutations and evolutionary transitions to argue for macromutationism.
Arguments on both sides have been biased by misconceptions of the developmental
effects of mutations. For example, the traditional view that mutations of
important developmental genes always have large pleiotropic effects can now be
seen to be a conclusion drawn from observations of a small class of mutations
with dramatic effects. It is possible that some mutations, for example, those in
cis-regulatory DNA, have few or no pleiotropic effects and may be the predominant
source of morphological evolution. In contrast, mutations causing dramatic
phenotypic effects, although superficially similar to hypothesized evolutionary
transitions, are unlikely to fairly represent the true path of evolution. Recent
developmental studies of gene function provide a new way of conceptualizing and
studying variation that contrasts with the traditional genetic view that was
incorporated into neo-Darwinian theory and population genetics. This new approach
in developmental biology is as important for microevolutionary studies as the
actual results from recent evolutionary developmental studies. In particular,
this approach will assist in the task of identifying the specific mutations
generating phenotypic variation and elucidating how they alter gene function.
These data will provide the current missing link between molecular and phenotypic
variation in natural populations.
PMID- 11005279
TI - The effects of subdivision on the genetic divergence of populations and species.
AB - An island model of migration is used to study the effects of subdivision within
populations and species on sample genealogies and on between-population or
between-species measures of genetic variation. The model assumes that the number
of demes within each population or species is large. When populations (or
species), connected either by gene flow or historical association, are themselves
subdivided into demes, changes in the migration rate among demes alter both the
structure of genealogies and the time scale of the coalescent process. The time
scale of the coalescent is related to the effective size of the population, which
depends on the migration rate among demes. When the migration rate among demes
within populations is low, isolation (or speciation) events seem more recent and
migration rates among populations seem higher because the effective size of each
population is increased. This affects the probability of reciprocal monophyly of
two samples, the chance that a gene tree of a sample matches the species tree,
and relative likelihoods of different types of polymorphic sites. It can also
have a profound effect on the estimation of divergence times.
PMID- 11005280
TI - Coevolutionary clines across selection mosaics.
AB - Much of the dynamics of coevolution may be driven by the interplay between
geographic variation in reciprocal selection (selection mosaics) and the
homogenizing action of gene flow. We develop a genetic model of geographically
structured coevolution in which gene flow links coevolving communities that may
differ in both the direction and magnitude of reciprocal selection. The results
show that geographically structured coevolution may lead to allele-frequency
clines within both interacting species when fitnesses are spatially uniform or
spatially heterogeneous. Furthermore, the results show that the behavior and
shape of clines differ dramatically among different types of coevolutionary
interaction. Antagonistic interactions produce dynamic clines that change shape
rapidly through time, producing shifting patterns of local adaptation and
maladaptation. Unlike antagonistic interactions, mutualisms generate stable
equilibrium patterns that lead to fixed spatial patterns of adaptation.
Interactions that vary between mutualism and antagonism produce both equilibrium
and dynamic clines. Furthermore, the results demonstrate that these interactions
may allow mutualisms to persist throughout the geographic range of an
interaction, despite pockets of locally antagonistic selection. In all cases, the
coevolved spatial patterns of allele frequencies are sensitive to the relative
contributions of gene flow, selection, and overall habitat size, indicating that
the appropriate scale for studies of geographically structured coevolution
depends on the relative contributions of each of these factors.
PMID- 11005281
TI - Fixation of clonal lineages under Muller's ratchet.
AB - For clonal lineages of finite size that differ in their deleterious mutational
effects, the probability of fixation is investigated by mathematical theory and
Monte Carlo simulations. If these fitness effects are sufficiently small in one
or both lineages, then the lineage with the less deleterious effects will become
fixed with high probability. If, however, in both lineages the deleterious
effects are larger than a threshold s(c), then the probability of fixation is
independent of the fitness effects and depends only on the initial frequencies of
the lineages. This threshold decreases with decreasing genomic mutation rate U
and increases with population size N. (For N = 10(5), we have s(c) approximately
= 0.1 if U = 1, and s(c) approximately = 0.015 if U = 0.1). Above the threshold,
the competition is not driven by the ratio of mean fitnesses of the lineages, but
by the relative sizes of the zero-mutation classes, which are independent of the
fitness effects of the mutations. After the loss of the zero-mutation class of a
lineage, the other lineage will spread to fixation with high probability and
within a short time span. If the mutation rates of the lineages differ
substantially, the lineage with the lower mutation rate is fixed with very high
probability unless the lineage with the larger mutation rate has very slightly
deleterious mutational effects. If the mutation rates differ by not more than a
few percent, then the lineage with the higher mutation rate and the more
deleterious effects can become fixed with appreciable probability for a certain
range of parameters. The independence of the fixation probability on the fitness
effects in a single population leads to dramatic effects in metapopulations:
lineages with more deleterious effects have a much higher fixation probability.
The critical value s(c), above which this phenomenon occurs, decreases as the
migration rate between the subpopulations decreases.
PMID- 11005282
TI - Patterns of parapatric speciation.
AB - Geographic variation may ultimately lead to the splitting of a subdivided
population into reproductively isolated units in spite of migration. Here, we
consider how the waiting time until the first split and its location depend on
different evolutionary factors including mutation, migration, random genetic
drift, genetic architecture, and the geometric structure of the habitat. We
perform large-scale, individual-based simulations using a simple model of
reproductive isolation based on a classical view that reproductive isolation
evolves as a by-product of genetic divergence. We show that rapid parapatric
speciation on the time scale of a few hundred to a few thousand generations is
plausible even when neighboring subpopulations exchange several individuals each
generation. Divergent selection for local adaptation is not required for rapid
speciation. Our results substantiates the claims that species with smaller range
sizes (which are characterized by smaller local densities and reduced dispersal
ability) should have higher speciation rates. If mutation rate is small, local
abundances are low, or substantial genetic changes are required for reproductive
isolation, then central populations should be the place where most splits take
place. With high mutation rates, high local densities, or with moderate genetic
changes sufficient for reproductive isolation, speciation events are expected to
involve mainly peripheral populations.
PMID- 11005283
TI - Overlapping generations can promote altruistic behavior.
AB - We use an inclusive fitness model to study the evolution of altruism in a patch
structured population in which there is positive probability of breeder survival
from one generation to the next. We find first that breeder survival promotes
altruism and second that there is a marked difference between benefits of
fecundity and benefits of survival. Under the first altruism is more strongly
favored, and under the second altruism is less strongly favored than in a
randomly mixing population.
PMID- 11005284
TI - The coevolution of parasites with host-acquired immunity and the evolution of
sex.
AB - Here I present a deterministic model of the coevolution of parasites with the
acquired immunity of their hosts, a system in which coevolutionary oscillations
can be maintained. These dynamics can confer an advantage to sexual reproduction
within the parasite population, but the effect is not strong enough to outweigh
the twofold cost of sex. The advantage arises primarily because sexual
reproduction impedes the response to fluctuating epistasis and not because it
facilitates the response to directional selection-in fact, sexual reproduction
often slows the response to directional selection. Where the cost of sexual
reproduction is small, a polymorphism can be maintained between the sexuals and
the asexuals. A polymorphism is maintained in which the advantage gained due to
recombination is balanced by the cost of sex. At much higher costs of sex, a
polymorphism between the asexual and sexual populations can still be maintained
if the asexuals do not have a full complement of genotypes available to them,
because the asexuals only outcompete those sexuals with which they share the same
selected alleles. However, over time we might expect the asexuals to amass the
full array of genotypes, thus permanently eliminating sexuals from the
population. The sexuals may avoid this fate if the parasite population is finite.
Although the model presented here describes the coevolution of parasites with the
acquired immune responses of their hosts, it can be compared with other host
parasite models that have more traditionally been used to investigate Red Queen
theories of the evolution of sex.
PMID- 11005285
TI - Population differentiation in an annual legume: genetic architecture.
AB - The presence or absence of epistasis, or gene interaction, is explicitly assumed
in many evolutionary models. Although many empirical studies have documented a
role of epistasis in population divergence under laboratory conditions, there
have been very few attempts at quantifying epistasis in the native environment
where natural selection is expected to act. In addition, we have little
understanding of the frequency with which epistasis contributes to the evolution
of natural populations. In this study we used a quantitative genetic design to
quantify the contribution of epistasis to population divergence for fitness
components of a native annual legume, Chamaecrista fasciculata. The design
incorporated the contrast of performance of F2 and F3 segregating progeny of 18
interpopulation crosses with the F1 and their parents. Crosses were conducted
between populations from 100 m to 2000 km apart. All generations were grown for
two seasons in the natural environment of one of the parents. The F1 often
outperformed the parents. This F1 heterosis reveals population structure and
suggests that drift is a major contributor to population differentiation. The F2
generation demonstrated that combining genes from different populations can
sometimes have unexpected positive effects. However, the F3 performance indicated
that combining genes from different populations decreased vigor beyond that due
to the expected loss of heterozygosity. Combined with previous data, our results
suggest that both selection and drift contribute to population differentiation
that is based on epistatic genetic divergence. Because only the F3 consistently
expressed hybrid breakdown, we conclude that the epistasis documented in our
study reflects interactions among linked loci.
PMID- 11005286
TI - Population differentiation in an annual legume: local adaptation.
AB - Studies of many plants species have demonstrated adaptive genetic differentiation
to local environmental conditions. Typically these studies are conducted to
evaluate adaptation to contrasting environments. As a consequence, although local
adaptation has been frequently demonstrated, we have little information as to the
spatial scale of adaptive evolution. We evaluated adaptive differentiation
between populations of the annual legume Chamaecrista fasciculata using a
replicated common-garden design. Study sites were established in three field
locations that are home to native populations of C. fasciculata. Each location
was planted for two years with seed from the population native to the study site
(home population) and populations located six distances (0.1-2000 km) from each
site (transplanted populations). Seeds were planted into the study sites with
minimum disturbance to determine the scale of local adaptation, as measured by a
home-site fitness advantage, for five fitness components: germination, survival,
vegetative biomass, fruit production, and the number of fruit produced per seed
planted (an estimate of cumulative fitness). For all characters there was little
evidence for local adaptation, except at the furthest spatial scales. Patterns of
adaptive differentiation were fairly consistent in two of the three sites, but
varied between years. Little genetic variation was expressed at the third site.
These results, combined with previous estimates of limited gene flow, suggest
that metapopulation processes and temporal environmental variation act together
to reduce local adaptation, except over long distances.
PMID- 11005287
TI - Fitness differences among diploids, tetraploids, and their triploid progeny in
Chamerion angustifolium: mechanisms of inviability and implications for polyploid
evolution.
AB - Theoretical models indicate that the evolution of tetraploids in diploid
populations will depend on both the relative fitness of the tetraploid and that
of the diploid-tetraploid hybrids. Hybrids are believed to have lower fitness due
to imbalances in either the ploidy (endosperm imbalance) or the ratio of maternal
to paternal genomes in their endosperm (genomic imprinting). In this study we
created diploids, tetraploids, and hybrid triploids of Chamerion angustifolium
from crosses between field-collected diploid and tetraploid plants and evaluated
them at six life stages in a greenhouse comparison. Diploid offspring (from 2x x
2x crosses) had significantly higher seed production and lower biomass than
tetraploid offspring (from 4x x 4x crosses). Relative to the diploid, the
cumulative fitness of tetraploids was 0.67. In general, triploids (from 2x x 4x,
4x x 2x crosses) had significantly lower seed production, lower pollen viability,
and higher biomass than diploid individuals. Triploid offspring derived from
diploid maternal parents had lower germination rates, but higher pollen
production than those with tetraploid mothers. Relative to diploids, the
cumulative fitness of 2x x 4x triploids and 4x x 2x triploids was 0.12 and 0.06,
respectively, providing some support for effect of differing maternal:paternal
ratios and endosperm development as a mechanism of hybrid inviability.
Collectively, the data show that tetraploids exhibit an inherent fitness
disadvantage, although the partial viability and fertility of triploids may help
to reduce the barrier to tetraploid establishment in sympatric populations.
PMID- 11005288
TI - The evolution of reproductive isolation in the ectomycorrhizal Hebeloma
crustuliniforme aggregate (Basidiomycetes) in northwestern Europe: a phylogenetic
approach.
AB - To reconstruct the evolution of reproductive isolation in the ectomycorrhizal
Hebeloma crustuliniforme aggregate (Basidiomycetes), phylogenetic relationships
were determined between strains that belong to a clade consisting of nine
intercompatibility groups (ICGs, biological species). Four of these nine ICGs are
partially compatible and belong to the H. crustuliniforme aggregate. Different
levels of partial compatibility have been found between these four ICGs. Between
ICGs 3 and 4, 15% of the combinations were compatible. One strain was compatible
with all isolates of both ICGs 3 and 4 and also with one isolate of ICG 2. Both a
nuclear phylogeny, based on ribosomal IGS sequence data, and a mitochondrial
phylogeny, based on a group-I intron located in the large subunit ribosomal RNA
gene (LrRNA), were reconstructed. The level of incompatibility was compared with
the phylogenetic history of individuals belonging to this clade. Different
relationships were found between the level of compatibility and the relative age
of the most recent common ancestor (MRCA) for different ICGs. On the one hand,
the evolution of incompatibility between ICGs 2 and 3/4 is most consistent with
the class of "divergence- first" models because a positive correlation was found
between the relative age of the MRCA and the level of incompatibility for ICG 2
versus 3/4. On the other hand, the lack of such a correlation for ICGs 3 and 4
shows that (partial) incompatibility between these ICGs has arisen without strong
divergence. The ecological (and to a lesser extent geographical) differences
found between ICGs 3 and 4 suggest that selection for incompatibility, associated
with host tree preference, has been important in the evolution of incompatibility
between these two ICGs. The incongruence between the nuclear and mitochondrial
trees for ICG 1 could be explained by a hybrid origin of this ICG, with different
donors of the mitochondrial and nuclear sequences.
PMID- 11005289
TI - Parental effects in Plantago lanceolata L. III. Measuring parental temperature
effects in the field.
AB - To determine the evolutionary importance of parental environmental effects in
natural populations, we must begin to measure the magnitude of these effects in
the field. For this reason, we conducted a combined growth chamber-field
experiment to measure parental temperature effects in Plantago lanceolata. We
grew in the field offspring of controlled crosses of chamber-grown parents
subjected to six temperature treatments. Each treatment was characterized by a
unique combination of maternal prezygotic (prior to fertilization), paternal
prezygotic, and postzygotic (during fertilization and seed set) temperatures.
Offspring were followed for three years to measure the effects of treatment on
several life-history traits and population growth rate, our estimate of fitness.
Parental treatment influenced germination, growth, and reproduction of newborns,
but not survival or reproduction of offspring at least one year old. High
postzygotic temperature significantly increased germination and leaf area at 17
weeks by approximately 35% and 2%, respectively. Probability of flowering and
spike production in the newborn age class showed significant parental genotype x
parental treatment interactions. High postzygotic temperature increased offspring
fitness by approximately 50%. The strongest contributors to fitness were
germination and probability of flowering and spike production of newborns. A
comparison of our data with previously collected data for chambergrown offspring
shows that the influence of parental environment on offspring phenotype is weaker
but still biologically meaningful in the field. The results provide evidence that
parental environment influences offspring fitness in natural populations of P.
lanceolata and does so by affecting the life-history traits most strongly
contributing to fitness. The data suggest that from the perspective of offspring
fitness, natural selection favors parents that flower later in the flowering
season in the North Carolina Piedmont when it is warmer. Genotypic-specific
differences in response of offspring reproductive traits to parental environment
suggest that parental environmental effects can influence the rate of
evolutionary change in P. lanceolata.
PMID- 11005290
TI - Chloroplast evolution in the Pinus montezumae complex: a coalescent approach to
hybridization.
AB - This study addresses the evolutionary history of the chloroplast genomes of two
closely related pine species, Pinus hartwegii Lindl. and P. montezumae Lamb
(subsect. Ponderosae) using coalescent theory and some of the statistical tools
that have been developed from it during the past two decades. Pinus hartwegii and
P. montezumae are closely related species in the P. montezumae complex (subsect.
Ponderosae) of Mexico and Central America. Pinus hartwegii is a high elevation
species, whereas P. montezumae occurs at lower elevations. The two species occur
on many of the same mountains throughout Mexico. A total of 350 individuals of P.
hartwegii and P. montezumae were collected from Nevado de Colima (Jalisco), Cerro
Potosi (Nuevo Leon), Iztaccihuatl/Popocatepetl (Mexico), and Nevado de Toluca
(Mexico). The chloroplast genome of P. hartwegii and P. montezumae was mapped
using eight restriction enzymes. Fifty-one different haplotypes were
characterized; 38 of 160 restriction sites were polymorphic. Clades of most
parsimoniously related chloroplast haplotypes are geographically localized and do
not overlap in distribution, and the geographically localized clades of
haplotypes include both P. hartwegii and P. montezumae. Some haplotypes in the
clades occur in only one of the two species, whereas other haplotypes occur in
both species. These data strongly suggest ancient and/or ongoing hybridization
between P. hartwegii and P. montezumae and a shared chloroplast genome history
within geographic regions of Mexico.
PMID- 11005291
TI - The fitness effects of spontaneous mutations in Caenorhabditis elegans.
AB - Spontaneous mutation to mildly deleterious alleles has emerged as a potentially
unifying component of a variety of observations in evolutionary genetics and
molecular evolution. However, the biological significance of hypotheses based on
mildly deleterious mutation depends critically on the rate at which new mutations
arise and on their average effects. A long-term mutation-accumulation experiment
with replicate lines of the nematode Caenorhabditis elegans maintained by single
progeny descent indicates that recurrent spontaneous mutation causes
approximately 0.1% decline in fitness per generation, which is about an order of
magnitude less than that suggested by previous studies with Drosophila. Two
rather different approaches, Bateman-Mukai and maximum likelihood, suggest that
this observation, along with the observed rate of increase in the variance of
fitness among lines, is consistent with a genomic deleterious mutation rate for
fitness of approximately 0.03 per generation and with an average homozygous
effect of approximately 12%. The distribution of mutational effects for fitness
appears to have a relatively low coefficient of variation, being no more extreme
than expected for a negative exponential, and for one composite fitness measure
(total progeny production) approaches constancy of effects. These results are
derived from assays in a benign environment. At stressful temperatures, estimates
of the genomic deleterious mutation rate (for genes expressed at such
temperatures) is sixfold lower, whereas those for the average homozygous effect
is approximately eightfold higher. Our results are reasonably compatible with
existing estimates for flies, when one considers the differences between these
species in the number of germ-line cell divisions per generation and the
magnitude of transposable element activity.
PMID- 11005292
TI - Evolution of poecilogony and the biogeography of North American populations of
the polychaete Streblospio.
AB - Invertebrate interspecific developmental patterns can be highly variable and,
taxonomically, are considered only weakly constrained. Intraspecifically, some
invertebrate species possess multiple developmental modes-a condition known as
poecilogony. Closer examination of most putative poecilogenous species, however,
has not supported poecilogony, but rather has uncovered hidden or cryptic
species. The polychaete Streblospio benedicti is a well-known, poecilogenous
species found along the coast of North America. We collected mitochondrial
cytochrome subunit I DNA sequence data from 88 individuals taken from 11
locations along the Atlantic, Gulf, and Pacific Coasts of the United States to
provide a phylogenetic framework from which to interpret intraspecific variation
in larval life history and brooding structure morphology in this species. Our
results are consistent with a recent revision of the species into two separate
species: S. benedicti, a pouched brooding form distributed along the Atlantic and
Pacific Coasts, and S. gynobranchiata, a branchiate brooding form in the Gulf of
Mexico. Contrary to the redescription, S. benedicti is paraphyletic because the
pouched brooding population in Vero Beach, Florida shows strong genetic affinity
with Gulf of Mexico populations (S. gynobranchiata). However, S. benedicti is a
true poecilogenous species, with both lecithotrophic and planktotrophic
individuals possessing identical mitochondrial DNA haplotypes. Crossbreeding
experiments further support the molecular phylogeny with reproductive isolation
demonstrated between, but not within, the major phylogenetic clades consistent
with the previously described species. The genetic break near Vero Beach,
Florida, corresponds to a well-known phylogeographic boundary, but the estimated
time of separation for the Streblospio spp., approximately 10 million years
before present, predates all other known phylogeographic subdivisions in this
area. This suggests that biogeographic sundering in this region is a recurrent
event. Divergence times within the major Streblospio spp. clades are recent and
indicate that changes in larval life history as well as brooding structure
morphology are highly plastic and can evolve rapidly.
PMID- 11005293
TI - Life-history correlates of evolution under high and low adult mortality.
AB - Life-history theory predicts evolutionary changes in reproductive traits and
intrinsic mortality rates in response to differences in extrinsic mortality
rates. Trade-offs between life- history traits play a pivotal role in these
predictions, and such trade-offs are mediated, at least in part, by physiological
allocations. To gain insight into these trade-offs, we have been performing a
long-term experiment in which we allow fruitflies, Drosophila melanogaster, to
evolve in response to high (HAM) and low (LAM) adult mortality rates. Here we
analyze the physiological correlates of the life-history trade-offs. In addition
to changing development time and early fecundity in the direction predicted, high
adult mortality affected three traits expressed early in life-body size, growth
rate, and ovariole number-but had little or no effect on body composition
(relative fat content), viability, metabolic rate, activity, starvation
resistance, or desiccation resistance. Correlations among lines revealed trade
offs between early fecundity, late fecundity, and starvation resistance, which
appear to be mediated by differential allocation of lipids.
PMID- 11005294
TI - Morphological intergration between development compartments in the Drosophila
wing.
AB - Developmental integration is the covariation among morphological structures due
to connections between the developmental processes that built them. Here we use
the methods of geometric morphometrics to study integration in the wing of
Drosophila melanogaster. In particular, we focus on the hypothesis that the
anterior and posterior wing compartments are separate developmental units that
vary independently. We measured both variation among genetically diverse
individuals and random differences between body sides of single individuals
(fluctuating asymmetry, FA). For both of these sources of variation, the patterns
of variation identified by principal component analyses all involved landmarks in
both the anterior and posterior compartments simultaneously. Analyses focusing
exclusively on the covariation between the anterior and posterior compartments,
by the partial least-squares method, revealed pervasive integration of the two
compartments, for both individual variation and FA. These analyses clearly
indicate that the anterior and posterior compartments are not separate units of
variation, but that the covariation between compartments is sufficient to account
for nearly all the variation throughout the entire wing. We conclude that
variation among individuals as well as the developmental perturbations
responsible for FA generate shape variation primarily through developmental
processes that are integrated across both compartments. In contrast, much less of
the shape variation in our sample can be attributed to the localized processes
that establish the identity of particular wing veins.
PMID- 11005295
TI - Courtship song recognition in the Drosophila melanogaster complex: heterospecific
songs make females receptive in D. melanogaster, but not in D. sechellia.
AB - The courtship song emitted by male wing vibration has been regarded as one of the
most important signals in sexual isolation in the species of the Drosophila
melanogaster complex. Inter- and intraspecific crosses were observed using males
whose wings were removed (mute) or females whose aristae were removed (deaf).
Females of D. melanogaster, D. simulans, and D. mauritiana mated with
heterospecific males in the song-present condition (cross between normal females
and winged males) more often than in the no-song condition (cross between normal
females and wingless males or between aristaless females and winged males) or
they showed no preference between the two conditions. It is possible that in
these females heterospecific courtship songs play a role as if they were
conspecific. In contrast, the females of D. sechellia mated with D. melanogaster
or D. simulans males in the no-song condition more often than in the song-present
condition, suggesting that they reject males with heterospecific song. Female
mate recognition depending on the courtship song in D. melanogaster, D. simulans,
and D. mauritiana is considered to be relatively broader and that in D. sechellia
narrower.
PMID- 11005296
TI - The role of the use of different host plants in the maintenance of the inversion
polymorphism in the cactophilic Drosophila buzzatii.
AB - Inversion polymorphisms often have been associated with fitness variation.
Cactophilic Drosophila buzzatii has been used widely for the study of the
maintenance of chromosomal variation. The purpose of this paper is to address the
relative importance of variable selection regimes associated with the use of
three different host cacti and antagonistic pleiotropy in the maintenance of
chromosomal variation. Using homokaryotypic stocks derived from several lines
homozygous for four second-chromosome arrangements, we show that inversions
significantly affect first-instar larva to adult viability (VT), developmental
time (DT) and adult thorax length (TL). We also show that the effects of
inversions on DT and VT are dependent on the cactus rearing media. The effects of
polymorphic gene arrangements on life-history traits suggest the existence of
trade-offs between early and late fitness components. The dosage of arrangement
2st, the ancestral gene order, was negatively correlated with DT and TL, whereas
flies carrying the derived arrangements 2j and 2jq7 had longer DTs and larger
TLs. Arrangements 2st and 2jq7 increased viability, at least in one of the cactus
media tested. Our results suggest that environmental heterogeneity, as
represented by the use of different cactus hosts and the trade-off between DT and
TL, may be involved in the maintenance of the polymorphism. In addition, our data
suggest that the chromosomal phylogeny may be decoupled from the evolution of the
genes affecting life-history traits linked to the inversion system.
PMID- 11005297
TI - Interspecific genetics of mate recognition: inheritance of female acoustic
preference in Hawaiian crickets.
AB - Female mating behavior plays a fundamental role in the divergent evolution of
mate recognition systems that may lead to speciation. Despite this important
role, the phenotypic and genetic bases of female mating behavior remain poorly
understood. In this study, I examine the shape of the female acoustic preference
function and estimate values for pulse rate preference in two species of Hawaiian
crickets, Laupala kohalensis and L. paranigra. In addition, I examine how
preference differences are inherited in hybrid crosses between these species.
Females expressed unimodal preference functions and were generally more attracted
to pulse rates characterizing their own species. Unimodal preference functions
also characterized F1 and backcross generations, with hybrid females expressing
preferences for intermediate pulse rates. Pulse rate preferences segregated in
the backcross generation. Mean pulse rate preference matched mean pulse rate in
both parental and hybrid generations. Based on F1 hybrids and segregation
patterns in backcross females, I show that changes in both signal and receiver
components of the mate recognition system are consistent with a multilocus model
of change through incremental steps. The results therefore suggest that ancestors
of the current species also expressed unimodal preference functions and that
changes in acoustic communication signals occurred through shifts in mean pulse
rates and pulse rate preferences among populations.
PMID- 11005298
TI - Reproductive character displacement and speciation in periodical cicadas, with
description of new species, 13-year Magicicada neotredecem.
AB - Acoustic mate-attracting signals of related sympatric, synchronic species are
always distinguishable, but those of related allopatric species sometimes are
not, thus suggesting that such signals may evolve to "reinforce" premating
species isolation when similar species become sympatric. This hypothesis predicts
divergences restricted to regions of sympatry in partially overlapping species,
but such "reproductive character displacement" has rarely been confirmed. We
report such a case in the acoustic signals of a previously unrecognized 13-year
periodical cicada species, Magicicada neotredecim, described here as a new
species (see Appendix). Where M. neotredecim overlaps M. tredecim in the central
United States, the dominant male call pitch (frequency) of M. neotredecim
increases from approximately 1.4 kHz to 1.7 kHz, whereas that of M. tredecim
remains comparatively stable. The average preferences of female M. neotredecim
for call pitch show a similar geographic pattern, changing with the call pitch of
conspecific males. Magicicada neotredecim differs from 13-year M. tredecim in
abdomen coloration, mitochondrial DNA, and call pitch, but is not consistently
distinguishable from 17-year M. septendecim; thus, like other Magicicada species,
M. neotredecim appears most closely related to a geographically adjacent
counterpart with the alternative life cycle. Speciation in Magicicada may be
facilitated by life-cycle changes that create temporal isolation, and
reinforcement could play a role by fostering divergence in premating signals
prior to speciation. We present two theories of Magicicada speciation by life
cycle evolution: "nurse-brood facilitation" and "life-cycle canalization."
PMID- 11005299
TI - Genetic evidence for assortative mating between 13-year cicadas and sympatric "17
year cicadas with 13-year life cycles" provides support for allochronic
speciation.
AB - Thirteen-year cicadas of brood XIX from northern Arkansas, Missouri, and southern
Illinois (lineage A) are known to be genetically different at two marker loci
(mitochondrial DNA and abdominal color) from 13-year cicadas to the south
(lineage B) that emerge in the same year. Because 17-year cicadas from all broods
(year classes) are indistinguishable from lineage A at these two marker loci,
previous workers suggested that the lineage A cicadas of 13-year brood XIX were
derived from 17-year cicadas by life-cycle switching (allochrony). Data presented
here show that, over the same northern geographic range, lineage A is also
present in 13-year cicadas belonging to brood XXIII (which always emerges four
years later than brood XIX). Detailed sampling along the putative life-cycle
switching boundary in 13-year brood XXIII revealed a previously unsuspected broad
zone of overlap where populations contained individuals of both lineages A and B.
Despite this sympatry, and previous reports of a lack of behavioral barriers to
interbreeding, a strong correlation between mitochondrial haplotype and abdominal
color suggests that assortative mating has taken place. Lineage A 13-year cicadas
from both broods XIX and XXIII are only found within a gap in the spatial
distribution of 17-year cicadas. This, in combination with the lack of
differentiation between lineage A 13- and 17-year cicadas at the marker loci and
new behavioral data for 13-year brood XIX, suggests a recent derivation of all
northern 13-year cicadas from the 17-year cicadas via life-cycle switching. We
discuss the implications of these allochronic shifts for speciation.
PMID- 11005300
TI - Tests of pleistocene speciation in montane grasshoppers (genus Melanoplus) from
the sky islands of western North America.
AB - There has a been a resurgence of debate on whether the Pleistocene glaciations
inhibited speciation. This study tests a model of Pleistocene speciation,
estimating the phylogenetic relationships and divergence times of 10 species of
montane grasshoppers, genus Melanoplus, using 1300 bp of the mitochondrial gene
cytochrome oxidase I (COI). Based on average pairwise distances (corrected for
multiple substitutions using Kimura's two-parameter model), all species appear to
have originated within the Pleistocene. Sequence divergences between species are
less than 4%, corresponding to divergence times less than 1.7 million years ago.
Branching patterns among the species suggest that speciation was associated with
more than one glacial-interglacial cycle. A likelihood-ratio test rejected a
model of simultaneous species origins, the predicted branching pattern if species
arose from the fragmentation of a widespread ancestor. These grasshoppers live in
an area that was previously glaciated and, as inhabitants of the northern Rocky
Mountain sky islands, underwent latitudinal and probably altitudinal shifts in
distribution in response to climatic fluctuations. Given the repeated
distributional shifts and range overlap of the taxa, there most likely has been
ample opportunity for population mixing. However, despite periodic glacial
cycles, with more than 10 major glaciations over the past million years and
climatic fluctuations over as short a time scale as 10(3) to 10(4) years, the
dynamic history of the Pleistocene did not preclude speciation. Although
relationships among some taxa remain unresolved, these grasshopper species, even
with their recent origins, exhibit genetic coherence and monophyletic or
paraphyletic gene trees. The frequency of glacial cycles suggests that the
speciation process must have been extremely rapid. These species of grasshoppers
are morphologically very similar, differing primarily in the shape of the male
genitalia. These characters are posited to be under sexual selection, may play an
important role in reproductive isolation, and are known to diverge rapidly. This
suggests the rapidity of evolution of reproductive isolation may determine
whether species divergences occurred during the Pleistocene glaciations.
PMID- 11005301
TI - Reinterpreting recapitulation: systematics of needlefishes and their allies
(Teleostei: Beloniformes).
AB - As needlefishes (Belonidae) grow, their jaws pass through a "halfbeak" stage that
resembles the adult jaw condition of the closely related family of halfbeaks
(Hemiramphidae). Based on this pattern, some authors have suggested that
halfbeaks are "developmentally arrested" or paedomorphic needlefish derivatives,
whereas others have supported the notion that needlefishes are descended from
halfbeak-like ancestors and that needlefish ontogeny thereby recapitulates
phylogeny. To test these ideas and to better understand evolutionary changes in
jaw ontogeny, phylogenetic relationships among genera of needlefishes, sauries
(Scomberesocidae), halfbeaks, and flyingfishes (Exocoetidae) were assessed using
mitochondrial (cytochrome b and 16S), nuclear (Tmo-4C4), and morphological
characters. The resultant tree provides several novel taxonomic findings: (1)
flyingfishes appear to be nested within halfbeaks; (2) sauries appear to be
nested within needlefishes; and (3) the Indo-West Pacific freshwater halfbeaks
appear to be most closely related to the needlefish/saury clade. The structure of
the tree falsifies the idea that halfbeaks are paedomorphic needlefishes.
Instead, halfbeaks are basal relative to needlefishes, fitting the pattern
predicted by the hypothesis of recapitulation. I discuss limitations to
phylogenetic perspectives on recapitulation based on discrete character data by
comparing aspects of von Baerian and Haeckelian views of the relation between
ontogeny and phylogeny.
PMID- 11005302
TI - Spatiotemporal reorganization of growth rates in the evolution of ontogeny.
AB - Heterochrony, evolutionary changes in rate or timing of development producing
parallelism between ontogeny and phylogeny, is viewed as the most common type of
evolutionary change in development. Alternative hypotheses such as heterotopy,
evolutionary change in the spatial patterning of development, are rarely
entertained. We examine the evidence for heterochrony and heterotopy in the
evolution of body shape in two clades of piranhas. One of these is the sole case
of heterochrony previously reported in the group; the others were previously
interpreted as cases of heterotopy. To compare ontogenies of shape, we computed
ontogenetic trajectories of shape by multivariate regression of geometric shape
variables (i.e., partial warp scores and shape coordinates) on centroid size.
Rates of development relative to developmental age and angles between the
trajectories were compared statistically. We found a significant difference in
developmental rate between species of Serrasalmus, suggesting that heterochrony
is a partial explanation for the evolution of body shape, but we also found a
significant difference between their ontogenetic transformations; the direction
of the difference between them suggests that heterotopy also plays a role in this
group. In Pygocentrus we found no difference in developmental rate among species,
but we did find a difference in the ontogenies, suggesting that heterotopy, but
not heterochrony, is the developmental basis for shape diversification in this
group. The prevalence of heterotopy as a source of evolutionary novelty remains
largely unexplored and will not become clear until the search for developmental
explanations looks beyond heterochrony.
PMID- 11005303
TI - Evolution of temporal isolation in the wild: genetic divergence in timing of
migration and breeding by introduced chinook salmon populations.
AB - The timing of migration and breeding are key life-history traits; they are not
only adaptations of populations to their environments, but can serve to increase
reproductive isolation, facilitating further divergence among populations. As
part of a study of divergence of chinook salmon, Oncorhynchus tshawytscha,
populations, established in New Zealand from a common source in the early 1900s,
we tested the hypotheses that the timing of migration and breeding are under
genetic control and that the populations genetically differ in these traits
despite phenotypic overlap in timing in the wild. Representatives of families
from two populations were collected within a day or two of each other, reared in
a common environment, and then released to sea from each of two different rivers,
while other family representatives were retained in fresh water to maturity. The
date of maturation of fish held in fresh water and the dates of return from the
ocean and maturation of fish released to sea all showed significant differences
between the two populations and among families within populations. The very high
heritabilities and genetic correlations estimated for migration and maturation
date indicated that these traits would respond rapidly to selection. Combined
with the results of related studies on these chinook salmon populations, it
appears that spawning time may not only evolve during the initial phases of
divergence, but it may play an important role in accelerating divergence in other
traits.
PMID- 11005304
TI - Reproductive burden, locomotor performance, and the cost of reproduction in free
ranging lizards.
AB - A reduction in the locomotor capacity of gravid females is considered to be a
cost of reproduction if it leads to an increased risk of mortality. In this
study, we measured the change in endurance between gravid and postgravid female
side-blotched lizards (Uta stansburiana) as a test of the cost of reproduction.
We also altered reproductive investment in some females by direct ovarian
manipulation (yolkectomy), which decreased reproductive burden by 30%. Regardless
of experimental treatment, all females had lower endurance when gravid. Endurance
was 28% lower in gravid females from the yolkectomy treatment and 31% lower in
the unmanipulated females relative to postoviposition females. The experimental
reduction in clutch mass resulted in a 21% increase in endurance of gravid
yolkectomy females relative to control females. Postovipositional endurance was
significantly higher in the yolkectomized females than unmanipulated females,
which suggests that the cost of reproduction carries over to postoviposition
performance. Unmanipulated females exhibited a significant negative association
between endurance and size-specific burden. Endurance was not correlated with
clutch size or size-specific burden in the yolkectomy females. Survivorship to
the second clutch was higher in the yolkectomy females. The results from a
logistic regression showed the probability of survival to the second clutch was
significantly and positively associated with endurance after controlling for the
effects of treatment. Our analyses demonstrated that the decrement in performance
associated with current reproductive investment represents a cost of reproduction
expressed as diminished locomotor performance and lowered survivorship to the
next clutch.
PMID- 11005305
TI - Experimental excursions on adaptive landscapes: density-dependent selection on
egg size.
AB - Theories of density-dependent natural selection suggest that intraspecific
competition will favor juveniles of high competitive ability. Empirical evidence
has been provided from laboratory selection experiments, but field studies are
lacking due to the logistical difficulties of experimentally manipulating
population densities in natural settings. Here, we present data from a decade
long experimental field study of side-blotched lizards, Uta stansburiana that
overcomes these difficulties. We tested the hypothesis that density-dependent
natural selection causes egg size to increase from early to late clutches in this
and many other species. Using a novel combination of environmental manipulations
of hatchling density and phenotypic manipulations of egg size, we demonstrate
that the nature of selection on egg size changes dramatically in the absence of
older competitors. The strength of selection on egg size among later-clutch
hatchlings released in areas without competitors from early clutches became
almost doubled in magnitude, compared to that among hatchlings released in the
presence of older competitors. These experimental findings demonstrate density
dependent natural selection on egg size; however, they contradict the classical
idea that egg size increases during the reproductive season because of
competition between early and late hatchlings. The results indicate that
competitive age or size asymmetries between early and late hatchlings can
override within-cohort asymmetries due to egg size. We suggest that competition
could be an important mediator of oscillating selection pressures in this and
other systems. Finally, we discuss the utility of "double-level," simultaneous
experimental manipulation of both phenotypic traits that are targets of selection
(e.g., egg size) as well the environmental agents of selection (e.g., population
density).
PMID- 11005306
TI - Sexual size dimorphism in shorebirds, gulls, and alcids: the influence of sexual
and natural selection.
AB - Charadrii (shorebirds, gulls, and alcids) have an unusual diversity in their
sexual size dimorphism, ranging from monomorphism to either male-biased or female
biased dimorphism. We use comparative analyses to investigate whether this
variation relates to sexual selection through competition for mates or natural
selection through different use of resources by males and females. As predicted
by sexual selection theory, we found that in taxa with socially polygynous mating
systems, males were relatively larger than females compared with less polygynous
species. Furthermore, evolution toward socially polyandrous mating systems was
correlated with decreases in relative male size. These patterns depend on the
kinds of courtship displays performed by males. In taxa with acrobatic flight
displays, males are relatively smaller than in taxa in which courtship involves
simple flights or displays from the ground. This result remains significant when
the relationship with mating system is controlled statistically, thereby
explaining the enigma of why males are often smaller than females in socially
monogamous species. We did not find evidence that evolutionary changes in sexual
dimorphism relate to niche division on the breeding grounds. In particular,
biparental species did not have greater dimorphism in bill lengths than
uniparental species, contrary to the hypothesis that selection for ecological
divergence on the breeding grounds has been important as a general explanation
for patterns of bill dimorphism. Taken together, these results strongly suggest
that sexual selection has had a major influence on sexual size dimorphism in
Charadrii, whereas divergence in the use of feeding resources while breeding was
not supported by our analyses.
PMID- 11005307
TI - Microsatellites can be misleading: an empirical and simulation study.
AB - It has been long recognized that highly polymorphic genetic markers can lead to
underestimation of divergence between populations when migration is low.
Microsatellite loci, which are characterized by extremely high mutation rates,
are particularly likely to be affected. Here, we report genetic differentiation
estimates in a contact zone between two chromosome races of the common shrew
(Sorex araneus), based on 10 autosomal microsatellites, a newly developed Y
chromosome microsatellite, and mitochondrial DNA. These results are compared to
previous data on proteins and karyotypes. Estimates of genetic differentiation
based on F- and R-statistics are much lower for autosomal microsatellites than
for all other genetic markers. We show by simulations that this discrepancy stems
mainly from the high mutation rate of microsatellite markers for F-statistics and
from deviations from a single-step mutation model for R-statistics. The sex
linked genetic markers show that all gene exchange between races is mediated by
females. The absence of male-mediated gene flow most likely results from male
hybrid sterility.
PMID- 11005308
TI - Population genetic structure of two ecologically distinct Amazonian spiny rats:
separating history and current ecology.
AB - Population history and current demographic and ecological factors determine the
amount of genetic variation within and the degree of differentiation among
populations. Differences in the life history and ecology of codistributed species
may lead to differences in hierarchical population genetic structure. Here, we
compare patterns of genetic diversity and structure of two species of spiny rats
in the genus Proechimys from the Rio Jurui of western Amazonian Brazil. Based on
the ecological and life-history differences between the two species, we make
predictions as to how they might differ in patterns of genetic diversity and
structure. We use mitochondrial sequence data from the cytochrome b gene to test
these predictions. Although both species maintain nearly the same number of
mitochondrial haplotypes across the sampled range, they differ in levels of
genetic diversity and geographic structure. Patterns of gene flow are also
different between the two species with average M-values of nearly three in P.
steerei and less than one in P. simonsi. Our initial predictions are largely
upheld by the genetic data and where conflicting hypotheses arise, we suggest
further studies that may allow us to distinguish among evolutionary scenarios.
Separating the effects of history and ongoing demography on patterns of genetic
diversity is challenging. Combining genetic analyses with field studies remains
essential to disentangling these complex processes.
PMID- 11005309
TI - Heritable variation in a family-diagnostic trait.
AB - Derived characters that have not changed during the diversification of a clade
provide traits that are diagnostic at higher taxonomic levels. The tetradynamous
stamen condition (four long and two short stamens) of the Brassicaceae is an
example of a diagnostic trait that has not changed during the diversification of
this large flowering plant family. We investigated one hypothesis that might
explain the long-term stasis of this trait-that tetradynamous stamens have
persisted because of an absence of genetic variation underlying the trait.
Through a sib-analysis with Raphanus raphanistrum and an artificial selection
experiment with Brassica rapa, we demonstrate that significant genetic variation
is present for the tetradynamous condition in both species and that the trait is
therefore not constrained from evolutionary change by a lack of heritable genetic
variation.
PMID- 11005310
TI - Habitat-related adaptive properties of plant cuticular lipids.
PMID- 11005311
TI - Effect of stressful and nonstressful growth temperatures on variation of
sternopleural bristle number in Drosophila melanogaster.
AB - The effect of stressful (31 degrees C) and nonstressful (25 degrees C) growth
temperatures on quantitative variation and developmental stability (fluctuating
asymmetry) of Drosophila melanogaster was examined in a short-term selection
experiment on sternopleural bristle number. Realized heritabilities based on 10
generations of selection in an upward direction did not differ between the two
temperature regimes, which indicated that additive genetic variation was not
affected by a high, stressful temperature. Phenotypic variability and fluctuating
asymmetry of sternopleural bristles were significantly higher under stressful
conditions when averaged over generations, although most pairwise comparisons in
separate generations showed nonsignificant differences between temperatures.
PMID- 11005312
TI - Biogeography of the southeastern United States: a comparison of salamander
phylogeographic studies.
AB - Most phylogeographic studies of species from the southeastern United States have
shown a simple east-west division of mtDNA variation. However, a study of the
salamander Ambystoma maculatum resulted in a more complex pattern that includes a
close affinity between populations from the Central Highlands of Missouri and
Arkansas and the Coastal Plain separated by a genetically distinct central group
of populations. We test the generality of this observation by surveying
mitochondrial DNA (mtDNA) variation in the closely related species A. talpoideum.
An Ambystoma-specific intergenic spacer was amplified and sequenced. The 26
resulting haplotypes varied from 380 to 800 base pairs, and alignments, including
the outgroup, required 101 insertions/deletions. Sequence divergence among
haplotypes ranged from 0.001 to 0.758. Population subdivision was extensive
(theta = 0.64). Phylogenetic analysis of A. talpoideum mtDNA sequence reveals a
close relationship between the populations from the Central Highlands and the
Coastal Plain. This result is similar to that obtained for A. maculatum, although
the A. talpoideum clade is not as well differentiated from its sister clades. We
discuss the differences and similarities between the two Ambystoma species and
previous studies and call for increased focus on multiple species with similar
ecologies as a way to detect subtle biogeographic events.
PMID- 11005313
TI - Modulation of the T cell receptor beta chain repertoire after heart
transplantation.
AB - BACKGROUND: In a previous study it was shown that pre-transplant blood
transfusion was associated with a better clinical outcome after heart
transplantation (HTx). In this study the effect of heart transplantation (HTx) on
the T cell receptor V beta chain (TCRVbeta) repertoire was investigated.
Therefore, we analyzed the TCRVbeta repertoire of patients after HTx to see
whether a correlation with clinical outcome could be observed. METHODS: Patients
were analyzed at four different time points: pre-HTx, less than 1 month post-Htx,
between 1 month and 2.5 month post-Htx and more than 2.5 months post-HTx. CD4+
and CD8+ T cells were purified from patient peripheral blood mononuclear cells
(PBMC). TCR beta chain usage was analyzed semiquantitatively by Southern blot
analysis. RESULTS: HTx affected the TCRVbeta repertoire in both the CD4+ and CD8+
T cell compartments in all patients. Changes in the TCRVbeta repertoire were most
pronounced within the CD8+ T cell subset. Interestingly, one patient showed
modulation in TCRVbeta chain usage predominantly in the CD4+ T cell compartment.
CONCLUSIONS: Modulation of TCRVbeta chain usage was detected in all patients
analyzed. No clear-cut relation was observed between TCRVbeta modulation after
transplantation and clinical outcome. In some cases modulations appeared to
concur with observed immunological events (clinically and/or in-vitro).
PMID- 11005314
TI - Clusterin may be involved in rat liver allograft tolerance.
AB - Little is known about the possible role of complement inhibitors on tolerance
induced by liver allografts. Clusterin, which is a plasma glycoprotein, inhibits
cytolytic membrane attack complex (MAC) of complement by binding to soluble C5b-7
complex. The role of clusterin in relation to the naturally achieved tolerance in
a rat orthotopic liver transplantation (OLT) has not been investigated before.
Here we determined the kinetics of clusterin expression at different post
transplantation time points in a tolerogenic model (DA-PVG) where rejection was
naturally overcome without any immunosuppressive drugs in comparison with the
syngenic OLT model (DA-DA). Peripheral blood and liver tissues were taken from
OLT at various post-operative time points. A strong expression of soluble
clusterin was observed on post-transplantation day 7, which occurred at the peak
of the rejection in this tolerogenic OLT model. The expression of clusterin
remained strong even after tolerance was achieved. The intensity of clusterin
expression was much stronger when compared with the syngenic OLT (DA-DA) model
after OLT. A strong expression of clusterin mRNA was also observed in the
tolerogenic model on post-OLT day (POD) 7 and the expression persisted when
compared with the syngenic model on post-OLT day 60. Our data have shown that the
strongest levels of clusterin during the reaction phase in tolerogenic OLT may be
involved in tolerance induction.
PMID- 11005315
TI - Anti-CD4 induced rat heart tolerance: no presence of primed T cells and
regulatory mechanisms for cytotoxic T cells.
AB - Treatment with anti-CD4 monoclonal antibody (mAb) (OX38) induces heart, but not
skin graft tolerance in WF (RT1u) to Lewis (RT1l) rat strain combinations. We
examined differences in cellular responses between heart-bearing and skin
rejected hosts that were both treated with anti-CD4 mAb. In the tolerant LEW rats
bearing WF heart transplants, the secondary WF heart but not skin grafts were
accepted. On the other hand, in anti-CD4 treated WF skin-rejected hosts, both
secondary WF heart and skin grafts were rapidly rejected. Spleen cells from anti
CD4 treated WF skin-rejected LEW rats but not from WF heart-bearing LEW rats
received the same treatment generated CTL after in vitro stimulation with
paraformaldehyde (PFA) treated donor WF stimulator spleen cells. Adoptive
transfer of spleen cells from WF skin-rejected LEW rats with or without anti-CD4
therapy into the tolerant LEW rats at the secondary WF heart transplantation
blocked the secondary heart graft acceptance. However, transfer of spleen cells
from WF heart-rejected rats without immunosuppression failed to block acceptance
of the secondary heart graft. Our results indicated the lack of primed T cells
and presence of regulatory mechanisms for tissue specific T cells in anti-CD4
treated heart bearing hosts.
PMID- 11005316
TI - Cytokine secretion in mixed lymphocyte culture: a prognostic indicator of renal
allograft rejection in addition to HLA mismatching.
AB - We have previously demonstrated significant inter-individual variations in
cytokine protein secretion between normal individuals and patients prior to renal
transplantation. In this study, pre-transplant patient vs. donor mixed lymphocyte
cultures (MLC) were set up between 57 renal allograft patient/donor pairs, and
secretion of cytokine protein (IL-2, IL-4, IL-6, IL-10 and IFN-gamma) into the
culture supernatant measured by ELISA. Significant inter-individual variations in
protein secretion in MLC were observed for all cytokines studied. Univariate
analysis demonstrated that high levels of IFN-gamma and IL-10 in MLC and
spontaneous IL-4, together with female donor sex and a high degree of HLA
mismatching (especially HLA-DR) were significantly associated with rejection.
However, multivariate analysis revealed the greatest risk of rejection (RR =
25.5, P = 0.003) was associated with a combination of high IL-10 secretion in MLC
and mismatching for at least four HLA antigens (HLA-A, -B and -DR). It remains to
be determined whether cytokine secretion in MLC is linked to cytokine gene
polymorphisms. In future, assays for measuring either cytokine secretion or
genetic polymorphisms may prove to be useful in aiding donor selection and
tailoring immunosuppressive therapy.
PMID- 11005318
TI - Flow-PRA evaluation for antibody screening in patients awaiting kidney
transplantation.
AB - Flow-PRA is a flow cytometric method for both anti-HLA class I and class II
antibody (Ab) detection. We evaluated this technique for Ab screening in patients
awaiting kidney transplantation. After having established a rigorous threshold
for positivity, a three-dilution difference in sensitivity between Flow-PRA and
complement-dependent cytotoxicity (CDC) persisted. The sensitivity of the method
was satisfactory since all CDC-positive sera were also found to be positive with
the Flow-PRA method. Discrimination between anti-HLA class I and class II Abs was
excellent. Furthermore, all sera responsible for a positive flow cytometry
crossmatch (FCXM) and a negative CDC-crossmatch (CDCXM) at the time of a putative
transplant were found to be positive with Flow-PRA beads. The specificity was
excellent for anti-class I Ab detection since no false positive serum was found.
On the other hand, the specificity was lower for anti-class II detection, since
8.3% (2/24) false positive results were detected among all the negative sera
tested. Overall, our results suggested that Flow-PRA should be of value for anti
HLA Ab screening prior to kidney transplantation.
PMID- 11005317
TI - The peripheral lymphocyte count predicts graft survival in DA to Lewis
heterotopic heart transplantation treated with FTY720 and SDZ RAD.
AB - OBJECTIVE: The new immunomodulator 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3
propanediol hydrochloride (FTY720) lowers the peripheral lymphocyte count (PLC)
by inducing migration of circulating lymphocytes to secondary lymphoid organs.
This effect is dose-dependent at low (up to 0.1 mg/kg per day) doses in rats. We
investigated the correlation between PLC and the later rejection, when FTY720 was
combined with RAD. METHODS: Heterotopic cardiac grafting was performed using the
DA-Lewis strain combination. FTY720 and RAD were administered as single daily
doses by gavage alone and in combination starting 3 days before to 28 days after
transplantation. Graft survival was monitored daily by palpation. PLC was
determined at 1 and 4 weeks, body weight (BW) weekly. Histologic evaluation of
grafted hearts was performed after rejection. MAIN FINDINGS: FTY720 at doses of
0.03, 0.1 and 0.3 mg/kg per day prolonged graft survival dose-dependently from 6
(placebo) to 7, 9.5 and 15 days median survival time (MST). RAD at doses of 0.3,
1 and 3 mg/kg per day delayed rejection to 8.5, 18 and 37.5 days MST. Very small
FTY720 doses added to the lower RAD doses were effective in maintaining grafts
throughout the treatment period and with normal weight gain, as opposed to
regimens with 1 mg/kg or more per day RAD, which resulted in delayed weight gain.
FTY720 lowered the PLC significantly and dose-dependently. The PLC correlated
well with graft survival [Spearman rank correlation (n = 30, rs = -0.75)].
CONCLUSIONS: Fully effective FTY720 + RAD combination regimens caused no side
effects with respect to the rats' general well-being or weight gain and were
better tolerated than equiactive RAD monotherapy, suggesting a broader
therapeutic window for the combinations. Under the experimental conditions, the
PLC decrease showed an interesting correlation with the anti-rejection effects in
these two-drug regimens. Thus, in rats the PLC is helpful for monitoring the
biological activity of FTY720 at low doses (< 0.1 mg/kg per day), i.e. in the
range of the steep part of its dose-response relationship.
PMID- 11005320
TI - Genetic conservation of the immunophilin-binding domains of human calcineurin A1
and A2.
AB - Calcineurin a calmodulin-dependent phosphatase plays a critical role in calcium
dependent activation of T-lymphocytes and is the major target for the inhibitory
actions of the immunosuppressive drugs Tacrolimus (FK506) and Cyclosporin A
(CsA). Calcineurin is a dimeric protein consisting of distinct A (catalytic) and
B (regulatory) subunits. In humans two separate genes, CNA1 and CNA2, encode the
calcineurin A (CNA) subunit. The region of CNA that interacts with Calcineurin B,
calmodulin, and immunosuppressive drugs bound to their receptors--the
immunophilins--has been identified to amino acids 281-414 (Greengard P, Allen PB,
Nairin AC. Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1
cascade. Neuron 1999;23:435). Our working hypothesis was that the differences in
patient response to calcineurin inhibitors could be a consequence of inherited
variations within their CNA genes. Single-strand conformational polymorphism
(SSCP) analysis of cDNAs derived from the coding region for amino acids 281-414
of CNA1 and CNA2 in 32 healthy Caucasians did not detect polymorphic variations
within these genes. These results suggest that this region is highly conserved
and cannot account for individual variation in response of patients to FK506 and
CsA treatment.
PMID- 11005319
TI - Anti-galactose-alpha(1,3) galactose antibody production in alpha1,3
galactosyltransferase gene knockout mice after xeno and allo transplantation.
AB - Antibodies (Abs) that mediate the hyperacute rejection and acute vascular
rejection/delayed xenograft rejection of pig organs in humans and Old World
primates are predominantly directed at a single carbohydrate epitope, galactose
alpha1,3-galactose (alpha1,3Gal). The T-cell dependence of elicited anti
alpha1,3Gal Ab responses in humans and Old World primates is controversial. In
this study we have characterized anti-alpha1,3Gal Ab production in mice with
disrupted alpha1,3-galactosyltransferase genes (GT-Ko mice) and determined the T
cell dependence of anti-alpha1,3Gal Ab responses, following xenograft and
allograft transplantation. GT-Ko mice produce natural anti-alpha1,3Gal IgM and
IgG in an age-dependent manner, however, these Abs could not elicit hyperacute
rejection nor affect the rate of cardiac xenograft (3-5 days) or allograft
rejection (7-9 days). Transplantation of xenogeneic Lewis rats hearts elicited
modest anti-alpha1,3Gal Ab, but vigorous xenoAb responses. The anti-alpha1,3Gal
Ab response was restricted to the IgM and IgG3 subclass while the xenoAb response
comprised IgM and all four IgG subclasses. Transplantation of allogeneic C3H
hearts elicited weak anti-alpha1,3Gal Ab responses that were primarily IgM, but
vigorous alloAb responses. Despite the restriction of elicited anti-alpha 1,3Gal
Ab responses to the IgM and IgG3 isotypes, these responses are T-cell dependent.
The ability of allografts to elicit weak anti-alpha1,3Gal but strong allo-Ab
responses, can be explained by the dependence of alpha1,3Gal-specific B cells on
cognate help from T cells.
PMID- 11005321
TI - Levels of mycophenolic acid and its glucuronide derivative in the plasma of
liver, small bowel and kidney transplant patients receiving tacrolimus and
cellcept combination therapy.
AB - In order to help assess the usefulness of mycophenolate mofetil (MMF) as an
immunosuppressive agent in recipients of organs other than kidneys, we measured
the trough levels of the active metabolite of MMF, mycophenolic acid (MPA), and
its inactive glucuronide derivative (MPAG), in the plasma of liver (n = 83) and
small bowel transplant patients (n = 15) receiving MMF in combination with
tacrolimus. These levels were compared with a group of renal transplant patients
(n = 25) receiving the same drug regimen. All patient groups were otherwise
comparable except the small bowel patient group which contained more pediatric
patients (average age 18.7 +/- 3.9 years), and, therefore, received a higher
average drug dose (in mg/kg). Despite this, these patients displayed the lowest
levels of MPA of any group (0.39 +/- 0.08 microg/ml, P < 0.001 vs. 1.10 +/- 0.17
microg/ml for liver transplant patients, P < 0.001 or 2.46 +/- 0.37 microg/ml for
renal transplant patients, P < 0.001). There were no statistically significant
differences in MPAG levels between any of the groups. Although preliminary, these
data demonstrate significant transplanted organ-specific differences in MMF
pharmacology and/or bioavailability, and suggest the need for separate evaluation
of MMF dosing for each transplant type.
PMID- 11005322
TI - Cyclosporine A sensitivity in vitro and P-glycoprotein expression in patients on
dialysis and after kidney transplantation.
AB - BACKGROUND: In allogeneic kidney transplantation the response to cyclosporine A
(CsA) is important for graft outcome. Although CsA therapy is controlled by drug
monitoring to ensure therapeutic CsA levels, the sensitivity to the effects of
CsA varies among individuals. Since CsA is an antagonist of cytostatic drugs in P
glycoprotein (Pgp)-mediated transport, increased Pgp expression might contribute
to an increased resistance to CsA. METHODS: The sensitivity of lymphocytes at
three different concentrations of CsA was tested in a non-radioactive lymphocyte
transformation test and related to Pgp expression as determined by flow cytometry
on mononuclear cells. Five groups, including healthy donors (CON; n = 25),
patients on dialysis (DIAL; n = 25), patients before transplantation (PTX; n = 5)
and after transplantation [short-term (ATX; n = 5) and long-term (LTX; n = 25)]
were investigated. RESULTS: In LTX, the sensitivity to CsA at 400 and 1000 ng/ml
was significantly different from CON and DIAL. Overall a higher sensitivity to
CsA was seen in patients after transplantation. In ATX, sensitivity to CsA was
significantly higher than in PTX at a concentration of 1000 ng/ml CsA. However,
comparing all groups no significant changes in Pgp expression were noted.
Analysing the relationship between CsA sensitivity and Pgp expression, no
significant heterogeneity could be observed between the different groups.
CONCLUSION: In conclusion, our data suggest that in vitro testing of CsA
sensitivity prior transplantation and Pgp expression monitoring yield independent
results and cannot substitute for each other as predictors of graft outcome. The
differential role of each test for the evaluation of CsA sensitivity or
resistance remains to be determined.
PMID- 11005323
TI - Treatment of chronic contained spontaneous esophageal perforations.
AB - Spontaneous esophageal perforations are associated with a high mortality and
morbidity without surgery. The treatment mortality for early (<24) and late (>24
h) spontaneous esophageal perforations is reviewed as well as all recent cases of
chronic spontaneous esophageal perforations. Chronic esophageal perforations with
mediastinal cavities may be best treated by internal drainage of the cavity into
the esophagus in order to convert the transmural perforation into an intramural
esophageal dissection.
PMID- 11005324
TI - Prevalence of Barrett's esophagus by endoscopy and histologic studies: a
prospective evaluation of 306 control subjects and 376 patients with symptoms of
gastroesophageal reflux.
AB - The classic endoscopic diagnosis of a Barrett's esophagus (BE) is based on the
finding of > or =3 cm, of distal esophagus covered by specialized columnar
epithelium. However, currently, it is based on the finding of intestinal
metaplasia (IM) at the squamous-columnar mucosal junction, independent of its
extent. The aim of this study was to determine the prevalence of Barrett's
esophagus by endoscopic and histological findings in control subjects and in
patients with symptoms of gastroesophageal reflux (GER). Three hundred and six
control subjects and 376 patients with symptoms of gastroesophageal reflux were
included in this prospective study. Patients with Barrett's esophagus were
classified in three groups as follows. 1. Intestinal metaplasia at the cardia.
When endoscopy showed non-Barrett's esophagus, but histological intestinal
metaplasia was found. 2. Short-segment Barrett's esophagus. When <3 cm, was
covered with tongues or finger-like or creeping substitution of distal esophagus.
3. Long-segment Barrett's esophagus. When > 3 cm, of distal esophagus was covered
by specialized columnar epithelium. Two biopsies at the antrum, four biopsies at
the squamous-columnar junction and one or two at the distal esophagus were taken.
In control subjects, 1.6% showed histological IM at the esophagogastric junction.
In patients with GER without esophagitis or with erosive esophagitis, IM was
found in 18% and 10.7% respectively. 'Short-segment' Barrett's esophagus was
three times more frequent than 'long-segment' Barrett's esophagus. Patients with
Barrett's esophagus were significantly older than the other groups. The presence
of complications or erosions, peptic ulcer or stricture were significantly more
frequent among patients with 'long-segment' Barrett's esophagus (p < 0.0001). The
prevalence of dysplasia was similar in all groups of patients with Barrett's
esophagus. Complications such as ulcers, stricture and dysplasia were exclusively
seen among patients with BE, whereas non-Barrett's patients did not exhibit these
complications. In control subjects, IM can be found in a low percentage of cases.
Among patients with symptoms of GER, the classic endoscopic diagnosis of a
Barrett's esophagus can underestimate this condition in 80% of the cases.
Patients with intestinal metaplasia at the cardia already present 17% of the
cases with low-grade dysplasia. In all patients with symptoms of GER, systematic
biopsies at the squamous-columnar junction should be taken.
PMID- 11005325
TI - Antireflux surgery, highly selective vagotomy and duodenal switch procedure: post
operative evaluation in patients with complicated and non-complicated Barrett's
esophagus.
AB - Antireflux surgery, highly selective vagotomy (HSV) and Roux-en-Y
duodenojejunostomy have been suggested for control of pathophysiological factors
involved in patients with Barrett's esophagus (BE). The aim of this study was to
evaluate prospectively the results of this technique in patients with complicated
(n = 21) and noncomplicated (n=45) BE. Complete evaluation of esophageal
function, endoscopic histologic and clinical control was carried out before and 2
years after surgery. Post-operative results show recurrence of ulcer in patients
with complicated BE, but no recurrence in patients with non-complicated BE.
Preoperative esophageal ulcer and stricture were present in 85.3% and 14.3%,
respectively, of patients with complicated BE. In this group, recurrence of these
complications was 38.1% and 9.5% respectively. The technique offers excellent
results in patients with non-complicated BE. However, in patients with
complicated BE, the recurrence rate is higher, mainly because of the persistence
of acid reflux into the esophagus.
PMID- 11005326
TI - Aminolevulinic acid-induced photodynamic therapy: safe and effective ablation of
dysplasia in Barrett's esophagus.
AB - Photodynamic therapy (PDT) is a treatment in which cell damage is achieved by the
action of light on a photosensitizer. The aim of this study was to assess the
value of PDT in the treatment of Barrett's esophagus with low-grade dysplasia
(LGD). Forty patients with dysplastic Barrett's esophagus were given
aminolevulinic acid (ALA) 30 mg/kg orally followed 4 h later by laser endoscopy.
Follow-up endoscopy and biopsies were performed at 1, 6 and 12 months. A
macroscopic response was seen in 33 out of 40 patients, with a median decrease in
columnar epithelial area of 30% (range 0-90%). Post-treatment biopsies showed no
dysplasia in 39 out of 40 patients, with LGD remaining in one case. This was
maintained at 6 and 12 months. There were no significant side-effects. This study
demonstrates that ALA-induced PDT provides safe and effective ablation therapy
for Barrett's esophagus and is particularly useful against dysplasia.
PMID- 11005327
TI - Barrett's mucosa, Barrett's dysplasia and Barrett's carcinoma: diagnostic
endoscopy without biopsy-taking does not suffice.
AB - Many gastroenterologists are of the opinion that endoscopic diagnosis of gastro
oesophageal reflux disease (GORD) suffices and that additional biopsies are not
necessary. The data obtained from 1068 consecutive patients with histologically
confirmed Barrett's oesophagus were analysed retrospectively. In 37.9% of the
patients, the histological diagnosis of Barrett's oesophagus was an incidental
finding, whereas 32.7% of Barrett's carcinomas were diagnosed only at histology
but not during endoscopy. Of the Patients with dysplasia, 92.4% were diagnosed
only by the pathologist. Our analysis shows that an endoscopic diagnosis
suspicious for Barrett's mucosa is made in 62.1% of the cases, carcinoma in 70%,
and dysplasia in only 7.6% of the cases. Also, because neoplasia is detected for
the most part at the invasive carcinoma state, but not in the dysplasia stage,
the diagnosis of Barrett's oesophagus, with and without dysplasia, needs to be
improved by additional biopsies for histopathological investigation.
PMID- 11005328
TI - Incidence of adenocarcinoma and mortality in patients with Barrett's oesophagus
diagnosed between 1976 and 1986: implications for endoscopic surveillance.
AB - The objective of this study was to investigate the incidence of oesophageal
adenocarcinoma and its contribution to mortality in patients with Barrett's
oesophagus, and to identify a subgroup of patients who may benefit from
endoscopic surveillance. This was a retrospective study of a cohort of 70
patients diagnosed in the endoscopy unit of a Scottish teaching hospital as
having Barrett's oesophagus between 1976 and 1986. Information was obtained from
case notes, endoscopy records, histology reports and death certificates. Patients
were included if they had: (a) columnar-lined oesophagus of at least 3 cm; (b)
histological confirmation; and (c) absence of cancer when endoscopically
diagnosed as having Barrett's oesophagus. The main outcome for the patients was
development of adenocarcinoma or death. Information was available for 59 of 70
patients (84%). Forty-four patients were confirmed to have Barrett's oesophagus
and were followed up for 418 patient-years. Only two patients developed
oesophageal adenocarcinoma, resulting in an incidence of one case in 209 patient
years, a 55-fold risk compared with age- and sex-matched population in Scotland.
Both these patients had intestinal metaplasia and Barrett's ulcer. The majority
(90%) of patients died as a result of causes unrelated to adenocarcinoma of
oesophagus. In patients under 70 years with intestinal metaplasia, 189 annual
endoscopies would have been required to detect one cancer. Adenocarcinoma is an
uncommon cause of mortality in patients with Barrett's oesophagus. Endoscopic
surveillance is unlikely to alter overall mortality in patients with Barrett's
oesophagus. However, by limiting endoscopic surveillance to patients under 70
years with intestinal metaplasia, the estimated cost per cancer detected can be
reduced to l23000.
PMID- 11005329
TI - Recurrence and survival after resection of adenocarcinoma of the gastric cardia.
Rotterdam Esophageal Tumor Study Group.
AB - In a retrospective study, the results after resection of carcinoma of the gastric
cardia in the era without neoadjuvant therapy or extended lymph node dissection
were evaluated. All 184 patients who underwent resection between January 1983 and
December 1993 were included. Recurrence of disease, survival and prognostic
factors were determined. The overall cumulative 5-year recurrence rate was 71%
and the survival rate 23%. Multivariate analysis identified locoregional lymph
node and distant metastases as the crucial prognosticators of recurrence of
disease and survival. These results were similar to those from a previous study
concerning our patients operated during the years 1983-88. The prognosis of a
resected cardiacarcinoma has remained unchanged in our hands over the past 10
years. These results stress the importance of exploring new ways, such as the use
of new diagnostic tools, to optimize preoperative patient selection and more
aggressive treatment regimens to improve final outcome.
PMID- 11005330
TI - Evaluation of the intestinal microflora in the rat model for esophageal
adenocarcinoma.
AB - Surgically induced duodenal reflux results in cancer development in the rat
esophagus. One proposed mechanism of carcinogenesis relies on the production of
carcinogens in the presence of bacterial overgrowth. Against this background,
intestinal microflora in the rat jejunum was analyzed before and after reflux
inducing surgery. Total gastrectomy and esophagojejunostomy were performed on
Sprague-Dawley rats to produce esophageal reflux of duodenal juice (n = 12).
Three days before surgery they were randomized into three groups: animals which
received tap water; animals which received acidified water at pH 1.8; and animals
subjected to oral decontamination with triple antibiotics. During surgery and at
autopsy after 2 weeks, intestinal juice was aspirated and analyzed immediately
for bacterial content. The physiologic microflora of the rat jejunum contained
Lactobacillus spp. and Bacteroides spp., both of which were resistant to the
antibiotic regimen. Bacterial overgrowth with fecal bacteria was found following
surgery. Acidified water did not alter the intestinal microflora. Triple
antibiotics eliminated Escherichia coli and Proteus spp. and reduced the
concentration of Enterococcus spp. Bacterial overgrowth by bacteria of the fecal
flora occurs in the rat model of esophageal adenocarcinoma with the potential to
catalyze the production of carcinogens.
PMID- 11005331
TI - Detection of bile reflux: in vivo validation of the Bilitec fibreoptic system.
AB - The Bilitec ambulatory bile reflux monitor is advocated for the assessment of
bile reflux. However, it has only been validated by bench top (in vitro) studies.
This in vivo study used controlled 'iatrogenic' episodes of bile reflux to
determine the ability of the Bilitec system to detect bile acids in the
oesophageal lumen. At least 10 ml of fluid was aspirated from the stomach of each
of 32 patients, and analysed quantitatively for total bile acids (TBA) and total
bilirubin (TB). An in vitro assessment of this fluid with the Bilitec probe was
performed initially. The Bilitec probe was then sited in the distal oesophagus,
and the gastric fluid was introduced into the mid-oesophagus, through a naso
oesophageal tube, as a series of 10-ml volumes of varying dilutions (1:8, 1:4,
1:2, undiluted) to simulate gastro-oesophageal reflux events. Intraoesophageal
bilirubin absorbance was compared with TBA and TB for each dilution. Both TBA and
TB values correlated strongly with bilirubin absorbance in vitro (r = 0.83, p <
0.0001 and r = 0.82, p < 0.0001 respectively). However, this relationship was
weaker in vivo (r = 0.64, p = 0.0001 and r = 0.68, p < 0.0001 respectively). Of
the dilutions which contained potentially injurious concentrations of bile acid
(>1 mmol/L), 77% were associated with absorbance >0.14 (currently accepted
absorbance threshold for oesophageal bile reflux). Although in vitro sensitivity
of the Bilitec probe to bile acids was excellent, in vivo sensitivity was less
reliable, and 23% of significant 'bile reflux' episodes did not exceed the
currently recommended Bilitec absorbance threshold for bile reflux. In contrast,
false-positive results were unlikely. These findings suggest that the overall
accuracy of the Bilitec system is probably sufficient for clinical use, although
this method is not sufficiently reliable to be regarded as the gold standard for
the evaluation of duodeno-oesophageal reflux.
PMID- 11005332
TI - Reflux and pH: 'alkaline' components are not neutralized by gastric pH
variations.
AB - The ability of the 'alkaline' components of reflux to cause harm in vivo is still
open to debate, although these components have been shown in vitro to be capable
of damaging the mucosa. The precipitation of bile acids and lysolecithin that
occurs at low pH values is the main reason for questioning in vivo mucosal
damage. This study was undertaken to determine the composition of gastric
aspirates at different original pH values and the degree of solubility of the
alkaline components when pH modifications are artificially induced. The samples
for chemical analysis were collected from indwelling nasogastric tubes after
surgical procedures that did not involve the upper gastrointestinal tract. Bile
acid and lysolecithin concentrations were assessed by means of dedicated methods.
Thirty-five samples were available for bile acid evaluation and 27 for
lysolecithin evaluation. Bile acid and lysolecithin assessments were repeated
after pH adjustment at 2, 3.5, 5.5 and 7. For easier assessment of the results,
three ranges of the original pH were selected (pH < 2, 2 < or = pH < 5, pH > or =
5). For each pH range, results were pooled together and compared with those in
the other pH ranges. Bile acid concentrations were 113+/-48, 339+/-90 and 900+/
303 (mean +/- s.e.m. micromol/L), respectively, in the three groups selected on
account of the different original pH values. Differences were significant (p <
0.001). Both taurine- and glycine-conjugated bile acids were represented even at
pH < 2. No major differences were observed in bile acid concentration with the
artificially induced pH variations. Lysolecithin concentrations were 5.99+/-3.27,
30.80+/-8.43 and 108.37+/-22.17 (mean +/- SEM microg/ml), respectively, in the
three groups selected on account of the different original pH ranges. Differences
were significant (p < 0.001). No significant differences in lysolecithin
concentration were detected with the artificially induced pH variations. In
conclusion, both bile acids and lysolecithin are naturally represented in the
gastric environment even at very low pH values, although their concentrations
decrease on lowering of the naturally occurring pH. Given the concentration
variability of bile acids and lysolecithin, further studies are needed to assess
the minimal concentration capable of mucosal damage in vivo.
PMID- 11005333
TI - Fundal gastritis as a potential cause of reflux oesophagitis.
AB - The transient lower oesophageal sphincter relaxations which allow reflux may be
due to altered afferent pathways from the fundus. We aimed to determine whether
fundal inflammation is the underlying cause. Two endoscopic biopsies were taken
from each of the gastric antrum and fundus in 25 asymptomatic controls with a
normal endoscopy (median age 54 range 13-83 years), and 33 patients with erosive
oesophagitis (median age 52, 11-78 years). No patient had taken acid suppression
therapy or antibiotics for at least 1 month. Sections were stained with
haematoxylin and eosin and Giemsa stain and examined in a blinded fashion by one
pathologist for the presence of gastritis (Sydney classification) and
Helicobacter pylori. Chronic gastritis was common in both groups, but was usually
mild. In Helicobacter pylori-negative subjects, there was significantly less
chronic gastritis in the antrum and the fundus in oesophagitis patients than in
controls (p < 0.05). When present, gastric atrophy was usually antral and mild in
severity. There was no difference in the incidence of gastric atrophy in patients
with oesophagitis compared with controls (24% compared with 40%; p > 0.05).
Chronic gastritis is not more common in patients with oesophagitis, and is
unlikely to play a part in the pathogenesis of this disease.
PMID- 11005334
TI - Comparison of clinical, endoscopic and functional findings in patients with
intestinal metaplasia at the cardia, carditis and short-segment columnar
epithelium of the distal esophagus with and without intestinal metaplasia.
AB - In recent years, the diagnosis of short segments of intestinal metaplasia lining
the distal esophagus has increased. The aim of the present study was to determine
the clinical, endoscopic, histologic and functional results in patients with
intestinal metaplasia at the cardia (IMC), carditis and short-segment columnar
epithelium (CE) lining the distal esophagus with and without intestinal
metaplasia. Four groups were studied: 48 patients with carditis, 105 patients
with IMC, 78 patients with short-segment CE (SSCE) without IM and 69 patients
with short-segment CE with IM. All had clinical questionnaire, endoscopic and
histological evaluation, manometric studies and measurements of acid and
bilirubin exposition of the distal esophagus over 24 h. Patients without IM were
found to be younger than those with IM. Erosive esophagitis was observed in
similar proportions, but hiatal hernia was present in patients with SSCE with or
without IM. Patients without IM had mainly cardial mucosa more than fundic
mucosa. However, patients with IM had almost exclusively cardial mucosa. Low
grade dysplasia was observed only in patients with IM. Manometric evaluation
demonstrated a structural defective lower esophageal sphincter in all groups.
Acid and duodenal exposures of the distal esophagus over 24 h were significantly
greater in patients with SSCE with IM. In the presence of pathologic
gastroesophageal reflux (GER), there are several histological changes at the
mucosa distal to the squamous columnar junction. The first metaplastic change is
one from fundic to cardial mucosa and, when duodenal reflux occurs, a second
metaplastic change to intestinal metaplasia from cardial mucosa occurs.
Therefore, in all patients with symptoms of GER, biopsies specimens distal to the
squamous columnar junction should be taken routinely.
PMID- 11005335
TI - The effect of cola consumption on oral mucosa in rats.
AB - Drinks that contain phosphoric acid have been shown to have erosive effects and
cola drinks are strongly acidic (pH 2.5). Gingivitis may be caused by dietary
acids. Therefore, this study analyses the interaction of Coca Cola consumption
and oral mucosal damage. Thirty rats were divided into three groups of 10. The
animals received saline (pH 7.0) or HCl acid buffered to pH 2.6 or Coca Cola (pH
2.6) per os with 24-h free access to these solutions. A biopsy was taken from the
front of the gingiva and the tongue. Histopathological analysis showed no
specific lesion and there were no differences among saline, Coca Cola and HCl
groups. Flow cytometric analysis was used to assess proliferative activity. In
the HCl acid and Coca Cola groups, cell cycle analysis showed that the effects of
Coca Cola and HCl acid in inducing oral mucosal damage are similar. In both Coca
Cola [G0/G1, 70.38+/-7.9; S, 28.06+/-10.13; G2/M, 1.62+/-2.80; proliferative
index (PI), 28.68+/-7.981 and HCI (G0/G1, 67.7+/-18.9; S, 27.8+/-17.5; G2/M,
4.4+/-3.8; PI, 30.9+/-20.98), the rat cell population G0/G1 and G2/M phases were
found to be low (p < 0.05) and the cell population S and PI phases were found to
be significantly elevated compared with the control group (p < 0.05) (G0/G1,
86.92+/-8.69; S, 9.8+/-1.21; G2/M, 3.25+/-2.87; P1, 13.2+/-8.7). This result was
reflected in the proliferative index, which is used as a measure of the
regeneration index. The data show that Coca Cola and HCl acid have similar
proliferative and regenerative effects on oral mucosa, and it is possible that
their regenerative effects are caused as a result of an irritant effect.
PMID- 11005336
TI - Esophagogastric fistula secondary to teflon pledget: a rare complication
following laparoscopic fundoplication.
AB - Laparoscopic fundoplication has become the standard operation for
gastroesophageal reflux disease. In our service, a laparoscopic fundoplication is
performed as a 2-cm floppy 360 degrees wrap with division of the short gastric
vessels and the fundoplication is sutured using a prolene 2/0 mattress suture
(Ethicon, USA) and buttressed laterally with two teflon pledgets (PTFE 1.85 mm;
low porosity, Bard, USA). We report a patient with post-operative dysphagia due
to an esophagogastric fistula caused by erosion of a teflon pledget. This is the
first such case in 734 laparoscopic fundoplications performed between January
1991 and December 1998. Reoperation was required, resulting in a prolonged
convalescence. A review of current literature has not revealed any similar cases.
Causes for this rare complication are postulated.
PMID- 11005337
TI - Inflammatory fibroid polyp of the esophagus.
AB - The case of a 76-year-old woman with a submucosal tumor of the esophagus, whose
principal symptoms were dysphagia and epigastric/retrosternal pain, is reported
here. Endoscopy, barium swallow and a CAT scan all pointed to extramucosal
localization. The lesion was located in the lower esophagus lying on the stomach
fundus. An ulcer in the region of the cardia complicated the tumor. Two sets of
conventional biopsies failed to detect malignancy, only inflammation and
intestinal metaplasia were seen in the specimens of the mucosa surrounding the
ulcer. The endoscopic ultrasonographic findings were an indistinct margin,
hypoechogenicity, homogeneous appearance and location within the second and third
echographic layer. The surgical resection of the tumor was complemented by an
anterior partial fundoplication. The histologic study revealed an inflammatory
fibroid polyp, which is a rare, benign, non-capsulated submucosal lesion composed
mainly of loose connective tissue and vessels, with an eosinophilic inflammatory
component. This lesion is seldom found in the esophagus.
PMID- 11005338
TI - Mismatched clinicopathological response after concurrent chemoradiotherapy for
thoracic esophageal cancer.
AB - We have been treating patients with operable thoracic esophageal cancer according
to our own protocol. It includes the initial concurrent chemoradiotherapy (CRT)
followed by continuous CRT or surgery. Patients with good response to initial
chemoradiotherapy were allowed to continue chemoradiotherapy, whereas the others
were treated with surgery. However, there were two cases which showed
discrepancies in the clinicopathological response. Both patients received initial
chemoradiotherapy, including two courses of cisplatin (100-120 mg), 5
fluorouracil (750-1000 mg for 4 days) and radiation (44-50 Gy). On completion of
the initial chemoradiotherapy, all diagnostic imaging modalities including barium
swallow, esophagoscopy, endoscopic ultrasonography and thoracic computed
tomography strongly implicated residual tumor with a reduction rate of 40-50%.
The patients underwent radical esophagectomy 15-20 days after initial
chemoradiotherapy. Pathological specimens only revealed thickening of the
esophageal wall due to inflammatory change without residual carcinoma. These
facts suggest the current limitations of diagnostic images in evaluating the
response to chemoradiotherapy.
PMID- 11005339
TI - Recurrent gastric carcinoma causing pseudoachalasia: case report.
AB - We report the case of a patient with a gastric remnant relapse of an antral
carcinoma resected 5 years before and presenting with the clinical feature of a
secondary achalasia (pseudoachalasia). In spite of the patient's 4-month history
of dysphagia and weight loss that suggested a malignant lesion, barium swallow,
repeated endoscopic biopsies and computed tomography (CT) scan of the upper
abdomen did not reveal any abnormalities to indicate a recurrence. However, in
the following months, because of worsening symptoms, a further CT scan was
performed and revealed thickening of the cardia and gastric wall. The patient
underwent an exploratory laparotomy that showed an unresectable lesion involving
the gastric fundus, the diaphragm and penetrating into the mediastinum, and
therefore a palliative jejunostomy was performed.
PMID- 11005340
TI - Confronting the problem of increasing antibiotic resistance.
AB - Significant increases in prevalence of resistance to antibiotics have been
observed in common pathogens of humans in the United States and worldwide. The
consequences of the appearance and spread of antibiotic resistance have included
increasing morbidity, mortality, and cost of health care. The fundamental cause
for the appearance and spread of antimicrobial resistance has been increasing
antimicrobial use. However, other factors contribute in both inpatient and
outpatient settings. Recognizing the important causes of increasing antibiotic
resistance in these settings has led to practical recommendations, which health
care facilities and outpatient practitioners will need to review, adapt, and
apply for maximum local effectiveness for progress to be made in addressing one
of the most challenging problems facing modern medicine.
PMID- 11005341
TI - Gambling in the south: implications for physicians.
AB - Three historical cycles of legalized gambling have occurred in the South.
Currently, every southern state has legalized some form of gaming. Adult past
year prevalence rates of problem gambling in southern states are within the
national range. Higher prevalence rates occur in states with casinos and multiple
forms of legalized gambling. States with lotteries have higher prevalence rates
of adolescent problem gambling. Problem gambling can cause stress-induced
physical diseases and psychiatric symptoms in gamblers and their families.
Physicians can reduce personal, family, and social costs of problem gambling
through increased awareness, strategic screening, and early intervention.
Treatment approaches include inpatient treatment centers, self-help fellowship
groups, and cognitive-behavioral and addiction-based psychotherapies. Although no
standard pharmacologic treatments for gambling disorders exist, use of selective
serotonin re-uptake inhibitors is under investigation. Referral resources are
available to physicians in states with state-funded treatment programs for
problem gamblers and/or state councils for problem gambling.
PMID- 11005342
TI - The intrauterine device: still misunderstood after all these years.
AB - The intrauterine device (IUD) is one of the most effective, safe, and economic
methods of contraception today. It is used by more women worldwide than any other
reversible method of birth control, yet less than 1% of women in the United
States use the IUD. Still remembering the tragedy of the notorious Dalkon Shield,
American pharmaceutical companies and clinicians have been wary about promoting
any IUD, leaving most physicians inadequately trained in the two IUDs available
in the United States. Most significantly, misconceptions about the IUD's safety,
mechanism of action, complication rates, and liability have severely limited the
utilization of the IUD by many practitioners and women in the United States who
may greatly benefit from it.
PMID- 11005343
TI - Combined blunt thoracic aortic and abdominal trauma: diagnostic and treatment
priorities.
AB - Combined blunt trauma to the thoracic aorta and abdomen challenges the surgeon
from a diagnostic and therapeutic standpoint. Appropriately prioritizing
diagnostic workup and treatment is critical to assuring patient survival. A
management approach that considers the patient's injuries and clinical condition
as well as the availability of aortography and cardiac surgery are essential.
Patients with blunt aortic injury who are hemodynamically unstable with signs of
intra-abdominal injury should have immediate abdominal exploration. Further
assessment of the aortic injury and surgical repair can be delayed until after
the critical intra-abdominal bleeding has been addressed. The stable patient who
has both blunt abdominal trauma and blunt thoracic aortic injury but has no signs
of ongoing abdominal hemorrhage should initially have arch aortography.
Additional abdominal diagnostic studies may be done but should not delay
indicated surgical repair of the aortic injury.
PMID- 11005344
TI - Dueling doctors.
AB - Formal "duels of honor" ruled upper-class conduct for centuries. That social
pressure could compel a choice of "death before dishonor" seems nearly
incomprehensible today. Physicians might have been expected to disdain dueling as
contrary to professional ethics, but a few rather colorful physicians did enter
the lists. Details of some of the most famous physician duels are summarized in
this article.
PMID- 11005345
TI - Striae gravidarum as a predictor of vaginal lacerations at delivery.
AB - BACKGROUND: Abdominal stretch marks found during pregnancy may be indicative of
poor skin elasticity. One who does not have stretch marks may have better skin
elasticity and may be less likely to tear perineal and vaginal tissue during
vaginal delivery. This study was conducted to determine whether striae gravidarum
could predict lacerations and their severity. METHODS: This prospective
observational study included 168 women having vaginal delivery of infants who
weighed more than 2,000 g. The absence or presence and degree of lacerations
involving the perineum, vagina, labia, and periurethral regions were studied with
a step-wise multivariate logistic regression analysis. RESULTS: Episiotomy was
found to prevent spontaneous lacerations. Abdominal stretch marks were found to
be statistically significant predictors of lacerations when controlling for
episiotomy. CONCLUSIONS: Patients with striae gravidarum are at higher risk for
lacerations at the time of vaginal delivery than patients who do not have
abdominal stretch marks.
PMID- 11005346
TI - Tuberculosis exposure in a day-care center: recommended management.
AB - BACKGROUND: This article describes the contact investigation, clinical
evaluation, and prophylactic treatment of the children and staff members in a day
care center after exposure to a teaching assistant with tuberculosis (TB).
METHODS: The investigation included baseline and follow-up tuberculin skin
testing, history and physical examinations, and chest radiographs. Directly
observed prophylactic therapy with isoniazid was recommended for all exposed
children with a negative evaluation and all children with positive skin test
reactions and normal chest radiographs. Treatment was discontinued in children
with negative skin test results at follow-up. Adult staff members were screened
with baseline and follow-up skin tests and were referred for chest radiographs if
skin test reactions were positive. RESULTS: In 3 of the 141 exposed children and
3 of the 41 adult staff members, tuberculin skin tests yielded positive results.
No active TB disease was found. CONCLUSIONS: Isoniazid prophylaxis, administered
by directly observed prophylactic therapy in the children, was effectively
administered and tolerated in the day-care setting.
PMID- 11005347
TI - Use of misoprostol for cervical ripening.
AB - BACKGROUND: Misoprostol, the prostaglandin E1 analog, is increasingly used for
cervical ripening and induction of labor. We evaluated our experience with
misoprostol in an open-label setting. METHODS: Patients were selected for
cervical ripening based on clinical profile. At 3 cm cervical dilation,
misoprostol was discontinued and other means of labor augmentation were used.
Over 13 months, 470 inductions of labor occurred, and 455 charts were available;
254 patients (56%) received misoprostol for cervical ripening, and 144 (32%)
received dinoprostone (prostaglandin E2). RESULTS: With misoprostol, mean time
from beginning of contractions until delivery was 7 hours, 30 minutes; vaginal
birth occurred in 85% of cases, and spontaneous labor occurred in 38%.
Hyperstimulation occurred in 4 cases (1.6%) and precipitate labor in 7 (3%). All
infants were discharged in excellent condition; one had a 5-minute Apgar score
<7, and 33 (13%) had meconium, none with aspiration. Twenty-three patients who
had had a previous cesarean section received misoprostol and delivered vaginally.
CONCLUSION: Misoprostol was found to be a safe and effective agent for cervical
ripening as part of labor induction.
PMID- 11005348
TI - Transcutaneous lumbar diskectomy for internal disk derangement: a new indication.
AB - BACKGROUND: Percutaneous diskectomy has been used effectively to treat lumbar
disk herniation. The purpose of this review was to determine whether
transcutaneous diskectomy is an effective surgical option for treating lumbar
internal disk derangement. METHODS: Comprehensive retrospective review via
personal interview included 103 consecutive patients available for long-term
follow-up. For determining results as excellent, good, fair, or poor, the
criteria included subjective relief of back and/or leg pain, ability to perform
preinjury job functions, residual physical restrictions, use of medications, and
need for subsequent surgery. Factors affecting results were statistically
analyzed. RESULTS: The overall success rate was 83%, with no statistically
significant differences in results based on sex, workers' compensation status, or
levels of diskectomy. CONCLUSIONS: The favorable results from this series
illustrate the high success rate of transcutaneous lumbar diskectomy in a
heterogeneous patient population. Coupling the rate of success with a low rate of
complications, transcutaneous lumbar diskectomy appears to be an effective,
minimally invasive treatment for internal disk derangement.
PMID- 11005349
TI - Pseudomyxoma peritonei manifesting as intestinal obstruction.
AB - Pseudomyxoma peritonei is an appendiceal tumor with distinct clinical and
pathologic features. It frequently presents a problem in diagnosis and
management. We report a case of pseudomyxoma peritonei, which initially appeared
with intestinal obstruction. This is a rare initial manifestation in patients who
have not had multiple surgical procedures. We review the literature and discuss
the unique clinical features and misconceptions surrounding pseudomyxoma
peritonei.
PMID- 11005351
TI - Secondary abdominal pregnancy in a Jehovah's Witness.
AB - A 35-year-old woman, gravida 2, para 1, aborta 0, arrived at our emergency
department with abdominal pain of more than 2 weeks' duration. Diagnostic pelvic
ultrasonography confirmed a 16-week intra-abdominal pregnancy. Hemoglobin level
was 6.9 mg/dL, and hematocrit value was 20.1%. The patient refused blood
transfusion on religious grounds. Laparotomy revealed 2,000 mL of blood in the
abdomen and a live fetus, with the placenta attached to the omentum and the
serosal surface of the right fallopian tube. Postoperative hemoglobin level was
2.8 mg/dL. The patient was transferred to another facility for hyperbaric oxygen
therapy, where she subsequently died. Abdominal pregnancy is rare, but has high
fetal and maternal mortality rates. Our patient's case was complicated, since she
was a Jehovah's Witness and refused lifesaving treatment on religious grounds.
Serious medical decisions were made, while respecting the autonomy of the
patient.
PMID- 11005350
TI - Hypercalcemia and T-cell lymphoma with acquired immunodeficiency syndrome:
occurrence without human T-cell leukemia virus-I.
AB - We describe the case of a patient with acquired immunodeficiency syndrome (AIDS)
who had a CD4 cell count of 60/microL, bilateral hilar adenopathy, and
hypercalcemia. Transbronchial biopsy showed T-cell anaplastic large cell
lymphoma. Serology was negative for human T-cell leukemia virus-I (HTLV-I). This
appears to be the first case of T-cell anaplastic large cell lymphoma occurring
in an AIDS patient with hypercalcemia who was seronegative for HTLV-I.
PMID- 11005352
TI - Reemergence of sucrose nephropathy: acute renal failure caused by high-dose
intravenous immune globulin therapy.
AB - Sucrose nephropathy was first described more than 50 years ago. The disorder is
characterized by acute renal failure caused by the uptake of sucrose by renal
proximal tubule cells with subsequent cellular swelling and occlusion of the
tubule lumen. Approximately 114 cases of renal failure have been associated with
high-dose intravenous immune globulin (IVIG) therapy. Almost all cases were
caused by preparations containing large amounts of sucrose. Clinicians should
consider using IVIG preparations containing no sucrose in patients who are at
high risk for renal failure. Risk factors include older age, baseline renal
failure, and volume contraction.
PMID- 11005353
TI - Traumatic asphyxia complicated by unwitnessed cardiac arrest.
AB - We report a case of traumatic asphyxia complicated by unwitnessed cardiac arrest
in which the patient has made a good, functional recovery. Traumatic asphyxia is
an uncommon clinical syndrome usually occurring after chest compression.
Associated physical findings include subconjunctival hemorrhage and purple-blue
neck and face discoloration. These facial changes can mimic those seen with
massive closed head injury; however, cerebral injury after traumatic asphyxia
usually occurs due to cerebral hypoxia. When such features are observed, the
diagnosis of traumatic asphyxia should be considered. Prompt treatment with
attention to the reestablishment of oxygenation and perfusion may result in good
outcomes.
PMID- 11005354
TI - Cocaine-associated ischemic colitis.
AB - Cocaine use can result in various gastrointestinal complications, including
gastric ulcerations, retroperitoneal fibrosis, visceral infarction, intestinal
ischemia, and gastrointestinal tract perforation. We report cocaine-associated
colonic ischemia in three patients and review the literature. Including ours, 28
cases have been reported, with a mean patient age of 32.6 years (range, 23 to 47
years); 53.5% were men and 46.5% were women. The interval between drug ingestion
and onset of symptoms varied from 1 hour to 2 days. Cocaine is a potentially life
threatening cause of ischemic colitis and should be included in the differential
diagnosis of any young adult or middle-aged patient with abdominal pain and
bloody diarrhea, especially in the absence of estrogen use or systemic disorders
that can cause thromboembolic events, such as atrial fibrillation.
PMID- 11005355
TI - Agenesis of the gallbladder.
AB - Agenesis of the gallbladder is rare. Three groups have been identified: those
with multiple fetal anomalies, asymptomatic cases, and symptomatic cases. Right
upper quadrant pain is present in 90% of the cases, nausea and vomiting in 60%,
and jaundice in 35%. Operative strategy is aimed at thorough exploration to
locate an aberrant gallbladder. We treated a 72-year-old woman with right upper
quadrant pain, nausea, and vomiting but no fever or jaundice. Physical
examination revealed right upper quadrant tenderness without rebound. The white
blood cell count was 10,300/mm3. Total bilirubin level was 1.6 mg/dL.
Ultrasonography revealed one gallstone and an enlarged common bile duct.
Laparoscopic cholecystectomy was converted to open technique after failure to
locate the gallbladder. On intraoperative cholangiogram, no gallbladder was
identified. A T-tube was placed.
PMID- 11005356
TI - Acute tumor lysis syndrome with choriocarcinoma.
AB - A 52-year-old man with retroperitoneal nodal, lung, and liver metastases from
choriocarcinoma received chemotherapy with etoposide, cisplatin, and bleomycin.
Within 48 hours of starting treatment, he had hypotension, hypoxemia, and anuria.
Laboratory values showed hyperuricemia, hyperkalemia, hyperphosphatemia,
hypocalcemia, and metabolic acidosis. He was placed on mechanical ventilation,
and hemodialysis was instituted, with marked improvement in renal function. A
second, shortened course of chemotherapy with carboplatin and etoposide was given
21 days later. However, on hospital day 48, the patient died of progressive
pulmonary insufficiency and cardiac arrest. This represents the first reported
case of acute tumor lysis syndrome after systemic chemotherapy for advanced
nonseminomatous germ cell cancer.
PMID- 11005357
TI - Primary nodal neuroendocrine (Merkel cell) tumor in a patient with HIV infection.
AB - Lymphadenopathy in the human immunodeficiency virus (HIV) can be of diverse
etiology, ranging from infection to cancer. A neoplasm of epithelial origin
manifested as inguinal lymphadenopathy without a primary lesion is rare. We
report a case of Merkel cell tumor confined only to a lymph node in a patient
with the acquired immunodeficiency syndrome (AIDS). We believe this is the first
report of primary nodal Merkel cell tumor in a patient with HIV. Because Merkel
cell tumor is a rare skin neoplasm with features suggestive of high malignant
potential, it is important to distinguish a primary nodal Merkel cell tumor from
malignant metastatic processes on the one hand and relatively benign causes of
adenopathy on the other.
PMID- 11005358
TI - Pyoderma gangrenosum and myelodysplastic syndrome.
AB - Pyoderma gangrenosum (PG) is a painful, often rapidly progressive, ulcerating
skin disorder frequently associated with systemic diseases. We report the case of
a patient with PG and an anemia. A bone marrow biopsy showed changes consistent
with one of the myelodysplastic syndromes, refractory anemia with ringed
sideroblasts. Patients with PG and anemia should have bone marrow biopsy if no
cause of anemia is readily apparent.
PMID- 11005359
TI - Subacute thyroiditis manifesting as fever of unknown origin.
AB - Subacute thyroiditis (SAT) usually occurs in women in middle age with a viral
prodrome, thyroid or neck tenderness, classic symptoms of thyrotoxicosis, and
elevated erythrocyte sedimentation rate (ESR). We report a case in an 81-year-old
man who initially had 2 days of fever to 101.2 degrees F, confusion, and
bilateral lower extremity weakness. Extensive evaluation was remarkable only for
the following laboratory values: thyrotropin (TSH) 0.02 microIU/mL, free
thyroxine (FT4) 3.1 ng/dL, free triiodothyronine (FT3) 6.0 pg/mL, and ESR 98
mm/hr. One week later, the patient had persistent fevers to 102 degrees F; no
source was found. The fever resolved, and 3 months later the patient had profound
hypothyroidism (TSH >44.0 microIU/mL, FT4 0.4 ng/dL, ESR 13 mm/hr). A painless
thyroid gland and atypical manifestations of hyperthyroidism are unusual in SAT.
When fever is of unknown origin, SAT should be considered even if classic
features are absent.
PMID- 11005360
TI - Cyclooxygenase-2 inhibitor celecoxib: a possible cause of gastropathy and
hypoprothrombinemia.
AB - Gastrointestinal side effects from nonsteroidal anti-inflammatory drugs (NSAIDs)
result mainly from inhibition of the enzyme cyclooxygenase (COX)-1; it is
responsible for the synthesis of prostaglandin E2, which leads to increased
mucosal blood flow, increased bicarbonate secretion, and mucus production, thus
protecting the gastrointestinal mucosa. In inflammation, COX-2 is induced,
causing synthesis of the prostaglandins in conditions such as osteoarthritis and
rheumatoid arthritis. Two NSAIDs (celecoxib and rofecoxib) with very high
specificity for COX-2 and virtually no activity against COX-1 at therapeutic
doses have been approved for clinical use. In trials of celecoxib and rofecoxib,
only 0.02% of patients had clinically significant gastrointestinal bleeding,
compared to a 1% to 2% yearly incidence of severe gastrointestinal side effects
with NSAIDs. Our patient had arthritis of the hips and chronic atrial
fibrillation and was on warfarin therapy for stroke prevention; less than a week
after starting celecoxib therapy, gastrointestinal bleeding and
hypoprothrombinemia occurred.
PMID- 11005361
TI - Cutaneous nephrocolonic fistula as a consequence of a kidney stone.
AB - We report an unusual case of cutaneous nephrocolonic fistula caused by a renal
calculus with perirenal infection. The diagnosis was made by fistulography and
computed tomography, after which nephrectomy and resection of the descending
colon were successful. We also review the literature on cutaneous nephrocolonic
fistulas.
PMID- 11005362
TI - Hazardous hedgehogs.
AB - The African pygmy hedgehog has recently become a fashionable exotic pet in the
United States, particularly in the South. As illustrated by the three cases
reported, this mammalian insectivore can be a carrier of fungi that cause human
dermatomycoses. The African pygmy hedgehog has also been associated with contact
urticaria and human salmonellosis.
PMID- 11005363
TI - Body temperature of newborns: what is normal?
AB - Medical records of 203 healthy full-term infants were reviewed to determine the
range of axillary temperatures for newborn infants, factors that affect
temperature and nursery management of infants with temperatures outside published
normal ranges. The mean birth temperature was 36.5 degrees C (S.D. = 0.6 degrees
C). Temperature was associated with birth weight (p<0.0005) and the presence of
maternal fever (p<0.0001) but not with type of environment or time of birth. The
mean temperature increased with age, rising 0.2 degrees C by 2-3 hours after
birth (p<0.0001) and 0.3 degrees C by 15-20 hours (p<0.0001). Among a subset of
114 eligible neonates the mean temperature dropped 0.2 degrees C after bathing
(p<0.0001). Although 17% of all temperatures measured were in the hypothermic (<
or =36.3 degrees C) range, the only response recorded by nursery staff consisted
of warming by modifying the environment, e.g., bundling. Blood cultures were
drawn from 51 infants (25%), 43 because of maternal intrapartum antibiotic
treatment for maternal fever or prolonged duration of ruptured amniotic membranes
(>24 hours) and none for evaluation of abnormal temperatures. No infants had
systemic infections and all were discharged in stable condition. Newborn axillary
temperatures in our nursery were considerably lower than what has been previously
described as "normal." Given the frequency of "hypothermia" and absence of
associated illness, we believe the reference range for newborn temperatures
should be expanded to include lower temperatures.
PMID- 11005364
TI - Significance of a cardiac murmur as the sole clinical sign in the newborn.
AB - A cardiac murmur is a very common finding in the first few days of life. It is
traditionally believed that lesions creating left-to-right shunts do not present
so early. This study was aimed to define and to classify the causes of a murmur
in a newborn with an otherwise normal examination. All echocardiograms performed
on newborns aged 1-5 days who were referred for evaluation of a murmur in a 3
year period were reviewed. Newborns with additional clinical signs or antenatal
diagnosis of a cardiac disease were excluded. Of 20,323 live births, there were
170 newborns referred for echocardiogram solely because of a murmur. Of these,
147 (86%) were found to have structural heart defects. The most common lesions
found were those creating left-to-right shunts (66%). Ventricular septal defect
was the most common single lesion (54/147, 37%), followed by patent ductus
arteriosus (34 newborns, 23%). The combination of both was found in 10 newborns
(7%). Six newborns (4%) had pulmonary valve stenosis and three (2%) aortic valve
stenosis. Seven newborns (5%) had unforeseen complex heart disease. For five of
them, delayed diagnosis would have resulted in potentially life-threatening
conditions. There was no correlation between the category of lesion and the age
of presentation. The audible threshold of a murmur correlated with a maximum
instantaneous gradient of 25 mm Hg (range 11-46 mm Hg). Thirteen percent of
newborns with isolated heart murmur had no identifiable structural heart disease.
These data suggest that most asymptomatic newborns presenting with a murmur in
the first days of life have structural heart disease. Some of the more serious
defects would not have been diagnosed without early echocardiography. A left-to
right shunt, particularly a ventricular septal defect, may cause a murmur even
the first day of life and is probably more common that has been acknowledged.
PMID- 11005365
TI - Risk behaviors and the prevalence of Chlamydia in a juvenile detention facility.
AB - The prevalence of Chlamydia trachomatis, a sexually transmitted disease, and the
association of selected behavioral risk factors were assessed in a population of
adolescents in two juvenile detention facilities. Urine was collected for
Chlamydia testing and a brief interview conducted for risk and demographic
information. Almost all of the 200 participants were sexually active, many before
the age of 13 years. The prevalence of Chlamydia infection was 22.2% among female
and 8.7% among male participants. Injection drug use was the only statistically
significant variable associated with infection. Education and community services
are necessary to break the cycle of infection for this high-risk population.
PMID- 11005366
TI - Syndrome of hypokalemic metabolic alkalosis and hypomagnesemia associated with
gentamicin therapy: case reports.
AB - Nephrotoxicity, as evidenced by renal insufficiency is a well-known consequence
of gentamicin therapy. We report two patients with gentamicin-induced syndrome of
hypokalemic metabolic alkalosis and hypomagnesemia. Both had complete recovery of
renal tubular function after cessation of antibiotic therapy. These cases
emphasize the need to routinely monitor patients receiving gentamicin therapy for
electrolyte abnormalities to avoid potential morbidity.
PMID- 11005367
TI - The value of book distribution in a clinic-based literacy intervention program.
AB - The purpose of this study was to determine whether anticipatory guidance at well
child visits (WCV) that included early literacy development and the provision of
books by the examining physician changed family literacy practices. It was
conducted in an inner-city pediatric clinic that serves as the continuity
practice site for pediatric and pediatric/internal medicine residents. There were
352 children (181 treatment: 171 control), aged 2 to 24 months, enrolled in this
prospective, controlled study. The health care providers underwent training on
literacy and on how to incorporate this information during WCV. Anticipatory
guidance on safety, development, and early literacy was given to all parents.
Additionally, the treatment group received an age-appropriate book at each WCV.
There were 1,263 visits made (686 treatment, 577 control). Questionnaires were
completed by parents on physician helpfulness and by physicians on parental
receptiveness. Parental ratings on physician helpfulness were higher in the
treatment group than in the control group (p<0.05). Physician's rating of
parental receptiveness was also higher in the treatment group than in the control
group (p<0.05). Two years after enrollment, mother-child pairs who received
guidance and a book were two times more likely to report enjoyment in reading
together than the controls who received guidance but no book. We conclude that
anticipatory guidance that included early literacy development and distribution
of books at WCV resulted in increased family literacy orientation, parental
receptiveness, and perception of physician helpfulness.
PMID- 11005368
TI - For Michael: those who can, teach.
PMID- 11005369
TI - Cough, rash, and dysuria in a preadolescent female.
PMID- 11005370
TI - Congenital cholesteatoma of the middle ear.
PMID- 11005371
TI - Fever in burned children and its association with infectious complications.
PMID- 11005372
TI - Intractable hypoglycemia in a patient with diabetes mellitus, bilateral
nephrectomy, and chronic active hepatitis.
PMID- 11005373
TI - Introducing Professor John H. Crowe, Anhydrobiosis and Biostabilization Section
Editor.
PMID- 11005375
TI - Expression of antisense hsp70 is a major determining factor in heat-induced cell
death of P-19 carcinoma cells.
AB - Overexpressed heat shock protein 70 (Hsp70) is known to be associated with
thermoprotection in a number of cell lines and transgenic animals. We
hypothesized that because overexpression of Hsp70 protects cells from lethal heat
stress, inhibition of expression should make cells susceptible to heat stress.
The model used for this study was a stably transfected P-19 carcinoma cell line
expressing antisense hsp70 under the control of the hsp70b promoter. The results
showed marked inhibition of Hsp70 expression after heat shock correlated with
heat-induced cell death. Hsp90 and Hsc70 protein expression were not affected by
the antisense construct. Unexpectedly, heme oxygenase (HO-1), another highly
inducible heat shock protein, was not induced after heat shock in the antisense
hsp70 cell line. Heat shock transcription factor-1 (HSF-1) was in a highly
phosphorylated state in the antisense cell line before and after heat shock. This
was in contrast to the untransfected control P-19 cells where HSF-1 was primarily
highly phosphorylated after heat shock. A control cell line expressing only the
vector, pMAMneo, without the antisense construct also showed partial loss of
Hsp70 induction but not increased cell death after heat shock. The findings
support the role of Hsp70 in thermoresistance.
PMID- 11005374
TI - GroEL binds a late folding intermediate of phage P22 coat protein.
AB - GroEL recognizes proteins that are folding improperly or that have aggregation
prone intermediates. Here we have used as substrates for GroEL, wildtype (WT)
coat protein of phage P22 and 3 coat proteins that carry single amino acid
substitutions leading to a temperature-sensitive folding (tsf) phenotype. In
vivo, WT coat protein does not require GroEL for proper folding, whereas GroEL is
necessary for the folding of the tsf coat proteins; thus, the single amino acid
substitutions cause coat protein to become a substrate for GroEL. The
conformation of WT and tsf coat proteins when in a binary complex with GroEL was
investigated using tryptophan fluorescence, quenching of fluorescence, and
accessibility of the coat proteins to proteolysis. WT coat protein and the tsf
coat protein mutants were each found to be in a different conformation when bound
to GroEL. As an additional measure of the changes in the bound conformation, the
affinity of binding of WT and tsf coat proteins to GroEL was determined using a
fluorescence binding assay. The tsf coat proteins were bound more tightly by
GroEL than WT coat protein. Therefore, even though the proteins are identical
except for a single amino acid substitution, GroEL did not bind these substrate
polypeptides in the same conformation within its central cavity. Therefore, GroEL
is likely to bind coat protein in a conformation consistent with a late folding
intermediate, with substantial secondary and tertiary structure formed.
PMID- 11005376
TI - Cycloheximide- and puromycin-induced heat resistance: different effects on
cytoplasmic and nuclear luciferases.
AB - Inhibition of translation can result in cytoprotection against heat shock. The
mechanism of this protection has remained elusive so far. Here, the
thermoprotective effects of the translation inhibitor cycloheximide (CHX) and
puromycin were investigated, using as reporter firefly luciferase localized
either in the nucleus or in the cytoplasm. A short preincubation of O23 cells
with either translation inhibitor was found to attenuate the heat inactivation of
a luciferase directed into the cytoplasm, whereas the heat sensitivity of a
nuclear-targeted luciferase remained unaffected. After a long-term CHX
pretreatment, both luciferases were more heat resistant. Both the cytoplasmic and
the nuclear luciferase are protected against heat-induced inactivation in
thermotolerant cells and in cells overexpressing heat shock protein (Hsp)70. CHX
incubations further attenuated cytoplasmic luciferase inactivation in
thermotolerant and in Hsp70 overexpressing cells, even when Hsp70-mediated
protection was saturated. It is concluded that protection by translation
inhibition is unlikely due to an increase in the pool of free Hsps normally
engaged in translation and released from the nascent polypeptide chains on the
ribosomes. Rather, a decrease in nascent chains and thermolabile polypeptides may
account for the heat resistance promoted by inhibitors of translation.
PMID- 11005377
TI - Attenuation of sepsis-induced apoptosis by heat shock pretreatment in rats.
AB - Apoptosis is a process by which cells undergo a form of non-necrotic cellular
suicide. Although it is a programmed process, apoptosis can be induced by various
stressors. During sepsis, apoptosis has been regarded as an important cause of
cell death in the immune system, leading to unresponsiveness to treatment. This
study was designed to investigate how prior heat shock induction can influence
the rate of apoptosis in animals that have experienced sepsis. Sprague-Dawley
rats were used, and experimental sepsis was induced by cecal ligation and
puncture (CLP). Animals in the heated group were anesthetized and received heat
shock by whole-body hyperthermia. They were sacrificed 9 h and 18 h after CLP as
early and late sepsis, respectively. Apoptosis was evaluated by "DNA ladder"
detection in agarose electrophoresis and Tdt-mediated dUTP nick end-labeling
(TUNEL) assay. Hsp72 was detected by Western blot analysis. The results showed
that the DNA ladder was detected most clearly in the thymus at the late phase of
sepsis with time course dependence, while it showed less clearly in heat shock
treated animals. Histopathological study by TUNEL assay obtained similar results
in the thymus, where the cortex was more susceptible to apoptosis than the
medulla. The Western blot analysis showed that the heat shock induced Hsp72
concomitant with an increase in Bcl-2:Bax ratio. In conclusion, heat shock
pretreatment prevents rats from sepsis-induced apoptosis that may account for the
better outcome of experimental sepsis. An increase in the Bcl-2:Bax ratio may in
part explain the molecular mechanism of the effect of heat shock pretreatment.
PMID- 11005378
TI - Characterization of the mouse gene for the heavy metal-responsive transcription
factor MTF-1.
AB - MTF-1 is a zinc finger transcription factor that mediates the cellular response
to heavy metal stress; its targeted disruption in the mouse leads to liver decay
and embryonic lethality at day E14. Recently, we have sequenced the entire MTF-1
gene in the compact genome of the pufferfish Fugu rubripes. Here we have defined
the promoter sequences of human and mouse MTF-1 and the genomic structure of the
mouse MTF-1 locus. The transcription unit of MTF-1 spans 42 kb (compared to 8.5
kb in Fugu) and is located downstream of the gene for a phosphatase (INPP5P) in
mouse, human, and fish. In all of these species, the MTF promoter region has the
features of a CpG island. In both mouse and human, the 5' untranslated region
harbors conserved short reading frames of unknown function. RNA mapping
experiments revealed that in these two species, MTF-1 mRNA is transcribed from a
cluster of multiple initiation sites from a TATA-less promoter without metal
responsive elements. Transcription from endogenous and transfected MTF-1
promoters was not affected by heavy metal load or other stressors, in support of
the notion that MTF-1 activity is regulated at the posttranscriptional level.
Tissue Northern blots normalized for poly A+ RNA indicate that MTF-1 is expressed
at similar levels in all tissues, except in the testes, that contain more than 10
fold higher mRNA levels.
PMID- 11005379
TI - Heat shock and arsenite induce expression of the nonclassical class I
histocompatibility HLA-G gene in tumor cell lines.
AB - The nonclassical histocompatibility class I gene HLA-G has a tissue-restricted
expression. To explore mechanisms involved in HLA-G transcriptional regulation,
we have investigated the effect of stress, including heat shock and arsenite
treatment, on HLA-G expression in tumor cell lines. We show that stress induces
an increase of the level of the different HLA-G alternative transcripts without
affecting other MHC class I HLA-A, -B, -E, and -F transcripts. A heat shock
element (HSE) that binds to heat shock factor 1 (HSF1) on stress conditions was
further identified within the HLA-G promoter. Considering the ability of HLA-G to
modulate the function of immunocompetent cells, we hypothesize a new feature of
HLA-G as a signal regulating the immune response to stress.
PMID- 11005380
TI - Formation of nuclear HSF1 granules varies depending on stress stimuli.
AB - In concert with the stress-induced activation of human heat shock factor 1
(HSF1), the factor becomes inducibly phosphorylated and accumulates into nuclear
granules. To date, these processes are not fully understood. Here, we show that
although stress caused by the proteasome inhibitors MG132 and clasto-lactacystine
beta-lactone induces the expression of Hsp70, the formation of HSF1 granules is
affected differently in comparison to heat shock. Furthermore, proteasome
inhibition increases serine phosphorylation on HSF1, but to a lesser extent than
heat stress. Our results suggest that, depending on the type of stress stimulus,
the multiple events associated with HSF1 activation might be affected
differently.
PMID- 11005381
TI - Potential targets for HSF1 within the preinitiation complex.
AB - Protein-protein interactions between human heat shock transcription factor 1
(hHSF1) and general transcription factors TFIIA-gamma, TFIIB, TBP, TAF(II)32, and
TAF(II)55 and positive coactivator PC4 were characterized in order to identify
potential targets of contact in the transcriptional preinitiation complex. These
contacts represent one of the final steps in the signal transfer of heat stress
to the transcriptional apparatus. TATA-binding protein (TBP) and transcription
factor IIB (TFIIB) were identified as major targets for HSF1 transcriptional
activation domains AD1 and AD2 based on in vitro interaction assays. TBP showed
affinity for AD2 and a fragment containing AD1, while the core domain of TFIIB
interacted primarily with the AD1 fragment. Interactions were also detected
between full-length HSF1 and the small subunit (gamma) of TFIIA. PC4 interacted
weakly with HSF2 and showed even less affinity for HSF1. Coimmunoprecipitation of
transiently expressed TBP in HeLa cells demonstrated that HSF1 AD2 and AD1+AD2
are able to bind TBP in vivo. Assays based on transcriptional interference
confirmed predictions that both TBP and TFIIB can interact with HSF1 activation
domains in HeLa cells. The negative regulatory region (NR) of HSF1 did not
interact with any general factors tested in vitro but did bind TFIID in nuclear
extracts through contacts that probably involve TATA associated proteins (TAFs).
These results suggest a model for transcriptional regulation by HSF1 that
involves a shift between formation of dysfunctional TFIID complexes with the NR
and transcriptionally competent complexes with the C-terminal activation domains.
PMID- 11005383
TI - The Escherichia coli heat shock protein ClpB restores acquired thermotolerance to
a cyanobacterial clpB deletion mutant.
AB - In both prokaryotes and eukaryotes, the heat shock protein ClpB functions as a
molecular chaperone and plays a key role in resisting high temperature stress.
ClpB is important for the development of thermotolerance in yeast and
cyanobacteria but apparently not in Escherichia coli. We undertook a
complementation study to investigate whether the ClpB protein from E coli
(EcClpB) differs functionally from its cyanobacterial counterpart in the
unicellular cyanobacterium Synechococcus sp. PCC 7942. The EcClpB protein is 56%
identical to its ClpB1 homologue in Synechococcus. A plasmid construct was
prepared containing the entire E coli clpB gene under the control of the
Synechococcus clpB1 promoter. This construct was transformed into a Synechococcus
clpB1 deletion strain (deltaclpB1) and integrated into a phenotypically neutral
site of the chromosome. The full-length EcClpB protein (EcClpB-93) was induced in
the transformed Synechococcus strain during heat shock as well as the smaller
protein (EcClpB-79) that arises from a second translational start inside the
single clpB message. Using cell survival measurements we show that the EcClpB
protein can complement the Synechococcus deltaclpB1 mutant and restore its
ability to develop thermotolerance. We also demonstrate that both EcClpB-93 and
79 appear to contribute to the degree of acquired thermotolerance restored to the
Synechococcus complementation strains.
PMID- 11005384
TI - Commentaries on Coburn 'The role of neo-liberalism'.
PMID- 11005382
TI - Aryl hydrocarbon (Ah) receptor levels are selectively modulated by hsp90
associated immunophilin homolog XAP2.
AB - The aryl hydrocarbon receptor (AhR) is a ligand-inducible transcription factor
that mediates biological responses to halogenated aromatic hydrocarbons. The
unliganded AhR is a cytoplasmic, tetrameric complex consisting of the AhR ligand
binding subunit, a dimer of hsp90, and the hepatitis B virus X-associated protein
2 (XAP2). The role of XAP2 as a member of the AhR core complex is poorly
understood. XAP2 shares significant homology with the immunophilins FKBP12 and
FKBP52, including a highly conserved, C-terminal, tetratricopeptide repeat (TPR)
domain. XAP2 forms a complex with hsp90 and the AhR but can also bind to both
independently. This binding is mediated by the conserved TPR domain. Single-point
mutations in this region are sufficient to disrupt the association of XAP2 with
both the AhR and hsp90 in cells. Cotransfection of the AhR and XAP2 in COS-1
cells results in increased AhR levels compared with cells transfected with the
AhR alone. In contrast, coexpression of the AhR with the TPR containing proteins
FKBP52, protein phosphatase 5 (PP5), or XAP2 TPR-mutants deficient in binding to
the AhR and hsp90 does not affect AhR levels and coexpression of the AhR with the
TPR domain of PP5 results in AhR down-regulation. These results demonstrate that
XAP2 is apparently unique among hsp90-binding proteins in its ability to enhance
AhR levels. A yellow fluorescent protein (YFP)-XAP2-FLAG was constructed and
biochemically characterized, and no loss of function was detected. YFP-XAP2-FLAG
was transiently transfected into NIH 3T3 and was found to localize in both the
nucleus and the cytoplasm when visualized by fluorescence microscopy. Treatment
of Hepa-1 cells with the hsp90-binding benzoquinone ansamycin, geldanamycin, and
the macrocyclic antifungal compound radicicol resulted in AhR but not XAP2 or
FKBP52 turnover. Taken together, these results suggest that XAP2/hsp90 and
FKBP52/hsp90 complexes are similar yet exhibit unique functional specificity.
PMID- 11005385
TI - Coburn's thesis: plausible, but we need more evidence and better measures.
PMID- 11005386
TI - Deeper than "neoliberalism". A reply to David Coburn.
PMID- 11005387
TI - Income inequality and health: expanding the debate.
PMID- 11005388
TI - Social change, market forces and health.
PMID- 11005389
TI - Unintended pregnancy and women's use of prenatal care in Ecuador.
AB - This paper assesses the relationship between unintended pregnancy--both unwanted
and mistimed and several dimensions of use of prenatal care among women in
Ecuador, where the level of unintended pregnancy has risen considerably in recent
years. Data were collected from a nationally representative sample of 3988 women
interviewed in the 1994 Demographic and Maternal-Child Health Survey.
Multivariate logistic regression was used to assess jointly the effect of
pregnancy intention status (unwanted, mistimed, planned) on three aspects of
prenatal care use while controlling for potential confounders. Women with
unwanted pregnancies were 32% less likely than women with planned pregnancies to
seek out prenatal care. Women with unwanted pregnancies were also 25% less likely
to initiate care in the first trimester and 29% less likely to receive at least
an adequate number of visits. Mistimed pregnancy was not associated with
receiving care, timely initiation of care or receiving an adequate number of
visits.
PMID- 11005390
TI - Social class and self-rated health: can the gradient be explained by differences
in life style or work environment?
AB - The purpose of the present paper is to describe differences in work environment
and life style factors between social classes in Denmark and to investigate to
what extent these factors can explain social class differences with regard to
changes in self-rated health (SRH) over a 5 year period. We used data from a
prospective study of a random sample of 5001 Danish employees, 18-59 years of
age, interviewed at baseline in 1990 and again in 1995. At baseline we found
higher prevalence in the lower classes of repetitive work, low skill discretion,
low influence at work, high job insecurity, and ergonomic, physical, chemical,
and climatic exposures. High psychological demands and conflicts at work were
more prevalent in the higher classes. With regard to life style factors, we found
more obese people and more smokers among the lower classes. The proportion with
poor SRH increased with decreasing social class at baseline. The follow-up
analyses showed a clear association between social class and worsening of SRH:
The lower the social class, the higher the proportion with deterioration of SRH.
There was no social gradient with regard to improved SRH over time. Approximately
two thirds of the social gradient with regard to worsening of SRH could be
explained by the work environment and life style factors. The largest
contribution came from the work environment factors.
PMID- 11005391
TI - "The lizard in the green bottle": "aging out" of problem drinking among Navajo
men.
AB - The Navajo exhibit a number of indicators suggesting the extent of significant
problems associated with drinking and alcohol abuse. Measures of alcohol-related
mortality and morbidity provide stark testimony regarding the shape and magnitude
of problem drinking among the Navajo. While these measures highlight patterns of
drinking that often result in social, physical, and psychological pathology,
there are other, less noted patterns of Navajo drinking. This paper describes a
salient, if often overlooked, pattern of Native American drinking by examining
the aging out phenomenon among Navajo men. Using narratives collected from former
problem drinkers, this paper describes the factors and motivations associated
with this sometimes dramatic change in drinking behavior. Several themes emerge
from these narratives that help explain the aging out process. These themes
include health concerns, religious involvement, living a traditional Navajo way
of life, and the responsibilities and life changes associated with child rearing.
This paper not only provides detail on a category of drinker and drinking
phenomena that is largely ignored in accounts of Native American drinking, but
also illustrates some of the values and meanings attached to drinking cessation
and highlights the relation between changes in drinking behavior and stages in
life course among Navajo men.
PMID- 11005392
TI - New Zealand children's health camps: therapeutic landscapes meet the contract
state.
AB - This paper surveys the history and current status of children's health camps in
New Zealand, and places these sites within the theoretical context of therapeutic
landscapes. The first health camp was established in 1919, and the seven current
camps provide respite, education and health care for approximately 4000 children
each year. We analyse the health-place relations inherent in the health camp
concept and suggest that the 'therapeutic landscape' idea developed by Gesler
provides a useful framework to explain the development of camps as sites for
enhancing child and family welfare. Specifically, we contend that changing
understandings of health and children have been closely linked with changing
perceptions of what is therapeutic about the camps. Survey data demonstrate that
contemporary restructuring of the welfare state has recast the role of health
camps and placed them in a precarious position in terms of both financial
viability and public acceptability. We conclude that the current status of health
camps is ambiguous given the pressures of deinstitutionalisation philosophies and
the regulatory environment of formal contracts between funders and providers.
PMID- 11005393
TI - Adult life experiences and health in early old age in Great Britain.
AB - In Britain and other developed countries older people comprise a large majority
of all those reporting long term illness or disability. However, most studies of
socio-demographic variations in health have focussed on those in younger age
groups. Moreover approaches to the study of health variations are often
fragmented. In this study we have adopted a life course approach to analyse
differentials in health in early old age. The data comes from the Retirement and
Retirement Plans Survey and follow-up, a two-wave study of persons aged 55-69 in
1988/9. As well as information on current circumstances, the data set includes
occupational, marital, and fertility history information. At baseline a
nationally representative sample of the population of Great Britain were
interviewed at home by trained interviewers (n = 3543). The sample was followed
up and in 1994, 2247 survivors were re-interviewed, a response rate of 70% (of
survivors). The data were weighted to adjust for non-response bias. Two outcome
measures were used: self rated health and presence or absence of disability
assessed from a scale derived from detailed questions on thirteen domains of
disability. The severity score used was that developed for the 1985/6 ONS Surveys
of Disability. The findings indicate that health and disability status at
baseline and at follow up were associated with socioeconomic and geographic
variables, such as proportion of adult life spent unemployed and residence
outside the Southeast of England; demographic factors, such as early age at
marriage and high parity; and experience of adverse events, such as the death of
a child and being dismissed from work. The results show that socio-economic,
demographic, and geographical and life events' factors are all associated with
health status in early old age and that integrated, rather than bifurcated,
approaches to the study of health differentials are needed.
PMID- 11005395
TI - Patient-centredness: a conceptual framework and review of the empirical
literature.
AB - A 'patient-centred' approach is increasingly regarded as crucial for the delivery
of high quality care by doctors. However, there is considerable ambiguity
concerning the exact meaning of the term and the optimum method of measuring the
process and outcomes of patient-centred care. This paper reviews the conceptual
and empirical literature in order to develop a model of the various aspects of
the doctor-patient relationship encompassed by the concept of 'patient
centredness' and to assess the advantages and disadvantages of alternative
methods of measurement. Five conceptual dimensions are identified:
biopsychosocial perspective; 'patient-as-person'; sharing power and
responsibility; therapeutic alliance; and 'doctor-as-person'. Two main approaches
to measurement are evaluated: self-report instruments and external observation
methods. A number of recommendations concerning the measurement of patient
centredness are made.
PMID- 11005394
TI - Factors associated with non-urgent utilization of Accident and Emergency
services: a case-control study in Hong Kong.
AB - Accident and Emergency Departments (A&E) have been a popular source of primary
care, and studies have shown that up to two thirds of patients attending A&E have
problems that could be managed by general practitioners (GPs). Although many
studies have found that patients of lower socio-economic class with less social
support have a higher utilization rate of A&E, some recent studies have revealed
contrary evidence. In this study 2410 patients were randomly selected from four
A&E at different times. The gold standard in differentiating true emergency cases
and GP cases was based on a retrospective record review conducted independently
by a panel of emergency physicians. Two emergency physicians reviewed each case
independently, and if their independent ratings were in agreement, this became
the gold standard. Patients classified as GP cases were given a telephone
interview, and a sample was selected and matched with cases from general out
patient clinics (GOPC) in the public sector by morbidity. Reasons for not
attending a private GP included closure of clinic, deterioration of symptoms,
GPs' inability to diagnose properly, and patients' wish to continue medical
treatment in the same hospital. Reasons why non-urgent patients did not choose to
attend the nearby public GOPC included affordability, closure of the GOPC,
patients' wish to continue treatment at the same hospital, GOPC too far away, no
improvement shown after visits to GOPC doctors, and GOPC doctors' inability to
make proper diagnoses. The reasons for high level of utilization of A&E services
are complex and reflect problems of delivery of GP services. There is an urgent
need for GPs to set up a network system to provide out of hours services, and
also for a better interfacing between primary and secondary care, and between
public and private sectors, so that patients can be referred back to GPs. Interim
clinical services provided to those non-urgent cases by nursing practitioners or
by GPs working in A&E could also facilitate discharge of patients to primary care
facilities.
PMID- 11005396
TI - The inertia of self-regulation: a game-theoretic approach to reducing passive
smoking in restaurants.
AB - Two alternate regulatory approaches can be used to reduce exposure to
environmental tobacco smoke in workplaces. The first is voluntary, self
regulation introduced by management, which is supported by common law and
occupational health legislation that emphasises the employers' 'duty of care'.
The second is public health legislation that bans smoking outright in enclosed
places. In Australia, self-regulation has succeeded in restricting tobacco
smoking in most indoor workplaces but has been a relative failure in the
hospitality industry. Claims that this reflects consumer preference by diners,
club and hotel patrons are not backed by survey evidence, typically showing large
majority support for non-smoking establishments. Insights from game theory show
why reliance on the duty of care is unlikely to succeed even when establishment
operators collectively support a non-smoking policy. Using plausible assumptions
about the net costs of unilaterally introducing smoking restrictions, what makes
good sense for society as a whole is likely to be the least profitable option for
an individual operator acting alone. Operators find themselves in the classic
prisoner's dilemma. If the aim of policy is to restrict smoking in public places
in order to protect the health of employees then game-theory predicts that public
health legislation banning smoking in enclosed places will be more effective than
self-regulation and reliance on the duty of care.
PMID- 11005397
TI - Social class differences in mortality using the National Statistics Socio
economic Classification--too little, too soon: a reply to Chandola.
AB - Chandola's (2000; Social Science and Medicine, 50(5), 641-649) claims that the UK
National Statistics Socio-economic Classification (NS-SEC) is not significantly
related to mortality are examined. It is shown that this result is likely to be
an artefact of the data and methods he uses. Other findings and interpretations
in his paper are also critically discussed. In the process, various theoretical,
measurement and analysis issues relating to the use of classifications such as
the NS-SEC in health research are reviewed.
PMID- 11005398
TI - Casualty, accident and emergency, or emergency medicine, the evolution.
PMID- 11005399
TI - A problem-based learning resource in emergency medicine for medical students.
AB - Emergency medicine is a relatively new specialty area within medicine, however
medical schools, students and standard setting bodies have recognised that
learning emergency medicine is integral to the training of medical students.
There are, however, significant problems with the delivery of emergency medicine
teaching including low teacher numbers, severely limited teaching time and lack
of suitable learning resources. This paper describes the process of development
of a learning resource, its format and content and summarises student feedback.
PMID- 11005400
TI - Acute occlusion of the retinal arteries: current concepts and recent advances in
diagnosis and management.
AB - PURPOSE/BACKGROUND: Central retinal artery occlusion (CRAO) is usually a blinding
event, and is not an infrequent presentation to the accident and emergency (A&E)
department. The evidence-base in support of current treatment options is weak.
METHODS: This paper reviewed the literature germane to the diagnostic,
therapeutic and prognostic aspects of retinal arterial occlusive disease.
RESULTS: The visual prognosis associated with CRAO remains poor, and current
therapeutic practices are of unproven benefit. The non-ophthalmologist in the A&E
department should lie the patient flat and give a stat dose of intravenous
acetazolamide in an attempt to improve the retinal perfusion pressure.
CONCLUSION: The management of acute occlusion of the central retinal artery has
not changed over the past 30 years, although the potential benefits of
superselective intra-arterial fibrinolytic therapy warrant evaluation in a
randomised controlled trial. The identification of underlying pathology is an
essential component of medical care, and all cases should be followed up by an
ophthalmologist because of the possibility of ocular rubeosis.
PMID- 11005401
TI - The focused trauma ultrasound examination. Can, and should, accident and
emergency physicians in the UK acquire this skill?
PMID- 11005402
TI - Neonatal head injuries.
AB - A retrospective case note review of head injuries in neonates admitted to the
Neonatal Surgical Unit in Glasgow between 1990 and 1996 (n=25) was carried out.
Most injuries were caused by a fall (68%) and resulted in scalp haematomata and
associated skull fractures in the majority of patients. Three neonates were
involved in high speed road traffic accidents, and these infants all had
intracranial pathology identified by computed tomography. Isolated skull
fractures were common and did not appear to be associated with any neurological
deficit. Nonaccidental injury was uncommon in this age group. Outcome was
excellent in the majority of patients (92%).
PMID- 11005403
TI - Next day telephone follow up of the elderly: a needs assessment and critical
incident monitoring tool for the accident and emergency department.
AB - BACKGROUND: Patients over the age of 75 years comprise an increasing proportion
of accident and emergency (A&E) department attendances. Within this group there
is a high incidence of comorbidity, which mandates effective discharge
coordination from the A&E department. OBJECTIVES: The aims of this study were to
assess the needs of these patients the day after discharge, target patients for
appropriate interventions and identify critical incidents. SETTING: The study was
undertaken in a district general hospital A&E department that has 62000 new
patient attendances per year. INCLUSION CRITERIA: Patients aged 75 years or over
who were discharged from the A&E department. EXCLUSION CRITERIA: Nursing home
patients. Patients without a telephone. STUDY DESIGN: Pre-discharge information
was collected from the medical notes. A community liaison nurse (CLN) then
contacted patients by telephone. A semistructured questionnaire was used to
assess patients. Patients were risk stratified and appropriate interventions
made. Interventions initiated by the CLN were scored from 1 to 6 based on the
level of input required. RESULTS: 551 patients or their carers were contacted by
telephone. Existing home support was felt to be insufficient in 44 (8%) cases and
in need of immediate intervention in a further 45 (8%) cases. Sixty five (11%)
Category 1 patients required no intervention, 223 (42%) Category 2 patients
required advice only, 107 (19%) Category 3 patients were referred to their GP,
127 (23%) Category 4 patients required a domicillary visit by a GP or a nurse, 26
(5%) Category 5 patients were at risk requiring urgent home assessment and three
Category 6 patients had to re-attend A&E. Advice was given by the CLN on a broad
range of issues and a wide range of health care services was accessed. Five
hundred and fifty nine referrals were made by the CLN after telephone assessment.
CONCLUSIONS: Telephone follow up of patients over 75 attending our A&E department
identified a number of areas where care could be improved before and after
discharge. This low cost, high quality intervention has the potential for
decreasing inappropriate return visits to the department by a vulnerable group of
patients as well as improving overall quality of care.
PMID- 11005404
TI - Biological tissue adhesive for multiple use in the accident and emergency
department.
AB - OBJECTIVE: To assess the strength of the glue and microbial contamination over 28
days from opening a vial of tissue adhesive in the accident and emergency
setting, and to quantify cost savings of repeated use of the vials. METHOD: (1)
Strips of reinforced nylon and a specially constructed piece of apparatus
designed to measure the force at which the glue gave way were used to measure the
strength of the tissue adhesive at various times after the glue was opened to
assess if the glue strength deteriorated over time. (2) Microbial contamination
of the glue was assessed. RESULTS: There was no deterioration in the glue
strength over time. There was no evidence of microbial contamination of the glue.
CONCLUSION: Cyanoacrylate tissue adhesive can safely be reused for a period of 28
days after opening with no risk of degradation of glue strength or contamination
with micro-organisms. In our department this represents a potential saving of
l5400 per year.
PMID- 11005405
TI - The capability of accident and emergency departments to safely decontaminate
victims of chemical incidents.
AB - OBJECTIVES: To evaluate the capability of accident and emergency (A&E)
departments in six health regions of England to safely decontaminate casualties
exposed to hazardous chemicals. METHODS: In January 1999 a postal questionnaire
was sent to the clinical director of all A&E departments in Trent, North and
South Thames, South and West, North West and, Anglia and Oxford Health Regions.
The questionnaire inquired about characteristics of the department,
decontamination facilities and equipment, and staff training. Nonresponders were
sent a second questionnaire and contacted by telephone if they failed to respond
to the second mailing. RESULTS: 308 of 326 departments identified (94%) returned
a questionnaire. There was no significant difference in response rate by region
(p = 0.99). Analysis was restricted to 154 major departments seeing more than
20000 new attendances per year. Of these 154 departments, 109 (71%) had a written
chemical incident plan but only 55 (36%) maintained a list of nearby industrial
chemical sites. Fifty nine departments (38%) stated that members of staff had
received training in the management of chemically contaminated casualties in the
preceding year. Eighteen departments (12%) possessed the level of personal
protective equipment (PPE) recommended for decontamination by the Ambulance
Services Association. Ninety six departments (62%) had a designated
decontamination room but only seven (7%) of them incorporated all the features
generally considered necessary for safe decontamination. Forty one units (27%)
had the capability to decontaminate casualties outside of the department either
with warm water from a shower attachment or with a mobile decontamination unit.
Thirty six departments (23%) had neither a decontamination room nor the ability
to decontaminate casualties outside the department. Only 16 units (10%) had both
adequate PPE and either a decontamination room or the capability to decontaminate
outside the department. CONCLUSIONS: This study has identified deficiencies in
the current NHS capability to respond to chemical incidents. To resolve this,
nationally recognised standards for decontamination facilities, equipment and
training should be formulated, agreed and implemented.
PMID- 11005406
TI - Referral to the accident and emergency department following the use of community
alarms.
AB - OBJECTIVES: To assess the degree of appropriate referral to the accident and
emergency (A&E) department following the use of a community alarm where a mobile
warden works in conjunction with the community alarm control centre. METHODS: 611
consecutive calls using community alarms underwent assessment and the
appropriateness of referral to the A&E department was considered. RESULTS: Of 542
requests for help 44 patients were transported to the A&E department (8.1%).
Twenty nine patients were admitted (5.3%) and 15 patients (2.8%) discharged home
from the A&E department after assessment or treatment, or both. Only three
patients (0.55%) had been referred to the A&E department inappropriately.
CONCLUSIONS: This study shows that where a mobile warden works in conjunction
with the community alarm control centre the number of inappropriate referrals to
the A&E department should be minimal.
PMID- 11005407
TI - Regular attenders to the accident and emergency department.
AB - OBJECTIVES: To examine the profile of regular attenders to an accident and
emergency (A&E) department, and to estimate the percentage of the overall
departmental workload attributed to this group of patients, together with the
resultant cost to the department of these attendances. METHODS: A retrospective
study of regular attenders to the A&E department at Hull Royal Infirmary was
conducted between 1 January 1998 and 30 June 1998. The information gathered
included age, sex, marital status, accommodation, investigations performed,
concurrent alcohol use, presenting complaints and disposal. RESULTS: The A&E
department at Hull Royal Infirmary sees approximately 87 000 new patients per
year. Forty regular attenders presented 475 times in six months accounting for
1.1% of the departmental workload. The most common presenting complaints were
overdose (27.4%), minor injuries (19%), alcohol intoxication (14%) and seizures
(10.5%). Eighty per cent of patients were single and 7.5% were of no fixed abode.
A total of 191 admissions resulted and the cost to the department for
investigations performed was between l2709.59 and l3739.85. The cost of
inhospital admissions was in excess of l34000. CONCLUSION: Improved management of
these patients together with a reduction in their alcohol intake may lead to a
significant reduction in both workload for accident departments and hospitals and
in the number of regular attenders.
PMID- 11005408
TI - Questionnaires of accident and emergency departments: are they reproducible?
AB - BACKGROUND: Questionnaires are commonly sent to accident and emergency (A&E)
departments to determine common practice and are often extrapolated to best
practice. AIMS: To determine if questionnaire based studies have a defined
population of A&E departments and whether studies are reproducible. METHODS: All
questionnaires in the Journal of Accident and Emergency Medicine were reviewed
and assessed for inclusion criteria, departments studied and study design.
RESULTS: 30 questionnaires were detected, 22 were postal, six telephone and two
did not state method of contact. Sample sizes ranged from 15 to 740 and inclusion
of A&E departments was highly variable according to geographical area, size of
department or consultant status. Seventeen (54.8%) did not state the source of
A&E department listings. Response rates ranged from 55-100%. Only three studies
undertook subset analysis according to either size or locality. CONCLUSIONS:
Questionnaire of studies A&E departments have poor methodology descriptions,
which means that many are not reproducible. Inclusion criteria are highly
variable and failure to analyse important subsets may mean that individual
departments cannot apply recommendations. Questionnaire studies relating to A&E
do not use a consistent well defined population of A&E departments. Information
in the studies is usually inadequate to allow them to be repeated.
PMID- 11005409
TI - An introduction to statistical inference--3.
AB - Statistics inference is used to make comments about a population based upon data
from a sample. In a similar manner it can be applied to a population to make an
estimate about a sample. It is commonly seen in medical publications when the
null hypothesis is being tested. This calculates the probability (p value) of a
type I error--that is, that a particular finding is attributable to chance. It is
also important to be aware of the chances of a type II error--that is, accepting
the null hypothesis when it does not apply. Sample size, point estimate and
variability are common factors that will affect the chances of making these two
types of errors. Interpreting results therefore needs to take these factors into
account as well as the clinical relevance of the findings. Statistical
significance does not necessarily mean clinical significance.
PMID- 11005410
TI - Towards evidence based emergency medicine:Best BETs from the Manchester Royal
Infirmary. Use of the McCoy laryngoscope in patients with suspected cervical
spine fracture.
PMID- 11005411
TI - Towards evidence based emergency medicine:Best BETs from the Manchester Royal
Infirmary. White cell count and diagnosing appendicitis in pregnancy.
PMID- 11005412
TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal
Infirmary. Oral acyclovir in acute cutaneous herpes zoster.
PMID- 11005413
TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal
Infirmary. Urinary trypsinogen to rule out acute pancreatitis in patients with
abdominal pain.
PMID- 11005414
TI - Journal scan.
PMID- 11005415
TI - Injuries sustained by aircrew on ejecting from their aircraft.
AB - This paper describes some of the injuries sustained by the aircrew who ejected
from their aircraft after a mid-air collision, and discusses the types of injury
that such patients may suffer.
PMID- 11005416
TI - Adult spinal cord injury without radiological abnormality.
AB - Spinal cord injury without radiological abnormality is rare in adults. A case is
described of a 61 year old man who fell 15 feet from a ladder striking his head
on a wall who presented with neck pain and with motor and sensory neurological
abnormalities in his limbs. Plain radiographs of the neck revealed no fractures
or dislocations. Further imaging with computed tomography and magnetic resonance
imaging revealed an osteophyte fracture with associated cord contusion at the C5
level. Careful neurological examination is essential in all cases of potential
spinal injury.
PMID- 11005417
TI - Hyperventilation: cause or effect?
AB - A young person presenting with shortness of breath is common to the accident and
emergency department. Usually this hyperventilation is anxiety related or a panic
attack, but sometimes it can be caused by a serious underlying condition like
pulmonary embolus. Acute shortness of breath in any patient should never be
dismissed lightly. It is important to realise that pulmonary embolus can present
without chest pain and with shortness of breath as the major symptom. Such
patients can be distinguished by close attention to history and examination, risk
factors for thromboembolic disease and the use of basic investigations
(electrocardiogram, chest radiography and arterial blood gas analysis). A serious
cause for shortness of breath must be excluded before labelling it as "hysteria"
or "panic".
PMID- 11005418
TI - Combined brachial plexus and vascular injury in the absence of bony injury.
AB - Neurovascular injury to the axillary vessels is well described in association
with fracture or dislocation involving the shoulder joint or the humerus. Such
injury however can also occur in the absence of bony injury. A case is presented
of damage to the axillary artery and brachial plexus following blunt trauma. This
case demonstrates that complex neurovascular damage can occur in the absence of
fracture or dislocation. The importance of a thorough clinical assessment is
highlighted and priorities with regard to diagnosis and management are discussed.
PMID- 11005419
TI - Acute cerebrovascular accident after minor trauma in a 1 year old.
AB - Acute cerebrovascular accident in an otherwise well child is a rare presentation.
A case is described where the diagnosis was delayed because of association with
minor trauma and a misleading diagnosis of soft tissue injury.
PMID- 11005420
TI - Trauma induced testicular torsion: a reminder for the unwary.
AB - Trauma induced testicular torsion is a well recognised entity, the incidence
being 4-8% in most studies reporting on testicular torsion. The signs and
symptoms of testicular torsion may easily be mistakenly attributed to preceding
testicular trauma if there was such an event. A patient is described with trauma
induced testicular torsion who presented on three occasions before a decision was
made to perform scrotal exploration. Unfortunately, an orchidectomy was the
outcome. The message that trauma can and not infrequently does precipitate
torsion, needs to be reiterated. Awareness of the entity and constant vigilance
is required of clinicians to avoid a delay in definitive treatment.
PMID- 11005421
TI - Retrieval of a metallic foreign body in the neck with a rare earth magnet.
PMID- 11005422
TI - Circ.com-plications.
PMID- 11005423
TI - An unusual diagnosis for a swollen limb.
PMID- 11005424
TI - An unusual cause of stridor.
PMID- 11005425
TI - A case of bilateral Lisfranc fracture--dislocations in a patient following
polytrauma.
PMID- 11005426
TI - Rabies in the accident and emergency department.
PMID- 11005427
TI - Consent in epidemiology: implications of history for public policy.
PMID- 11005428
TI - Strontium-90 in newborns and childhood disease.
AB - Radioactive strontium-90 concentrations in baby teeth obtained from Suffolk
County, New York, rose steadily during the 1980s. Recent levels of strontium-90
are similar to those reported for babies born in the late 1950s-at the height of
atmospheric nuclear weapons testing in Nevada. Strontium-90 concentrations
increased concomitantly with increases in cancer incidence among Suffolk children
under the age of 5 y, a result that mimicked parallel trends observed in the
1950s and early 1960s. Given that effects of strontium-90 on developing cells are
most pronounced during the fetal and infant periods, escalating levels should be
viewed as a factor in the recent decline in various child health status measures.
PMID- 11005429
TI - Blood lead secular trend in a cohort of children in Mexico City. II. 1990-1995.
AB - The authors determined the secular trend in blood lead levels in a cohort of 91
children born in Mexico City between 1987 and the beginning of 1993. The authors
grouped children by calendar year in which they reached 36 mo of age (i.e., 1990
1995), and their blood lead levels were measured every 6 mo during a 66-mo
period. The overall geometric mean blood lead level was 8.6 microg/dl (range =
1.0-61.0 microg/dl). A repeated measures analysis of variance revealed a
significant downward linear trend in blood lead levels by year (p < .001)--from
an estimated marginal geometric mean of 14.2 microg/dl in 1990 to 6.3 microg/dl
in 1995. There was also a significant linear age effect (p < .001); blood lead
levels generally fell during the 36th-66th mo. Family use of lead-glazed pottery
significantly elevated blood lead levels (p = .006), and the effect magnified as
age increased (Age x Pottery Interaction [p = .014]). Although the overall
downward trend in blood lead levels during the time period described corresponded
to a reduction in various sources of lead exposure, there was no alteration in
production, distribution, or use of leaded pottery. Currently, use of lead-glazed
ceramic pottery is one of the most profound sources of lead exposure in the
Mexican population.
PMID- 11005430
TI - A new technology to measure skin absorption of vapors.
AB - Skin vapor absorption is one of the major exposure routes for some widely used
chemicals (e.g., 2-methoxy ethanol), but a good apparatus with which exposure can
be measured is currently unavailable. In this study, a polished stainless-steel
chamber-combined with computer-controlled auto-feedback software and hardware,
real-time gas sensors, and an auto-injection microsyringe-was proposed as new
technology. In addition, the machines had activated-charcoal tubes and cold
traps, both of which simulated the skin uptake and validated the reliability of
the proposed system. The exposure concentrations, relative humidity, and
temperature were effectively controlled at 25+/-0.5 ppm (or 300+/-10 ppm), 80+/
2%, and 27.5+/-0.5 degrees C, respectively. The relative errors between the
quantity of 2-methoxy ethanol collected in either the charcoal tubes or the cold
traps and the quantity of ME injected to maintain a constant exposure were less
than 5%. The authors also used this new technology to successfully measure skin
absorption of ME vapor in 6 volunteers. The authors concluded that this new
technology is a direct, continuous, noninvasive, and simple tool with which to
measure skin absorption of vapors.
PMID- 11005431
TI - Biomonitoring study of people living near or working at a municipal solid-waste
incinerator before and after two years of operation.
AB - The authors conducted a biomonitoring study in the town of Mataro, Spain, of 104
subjects who lived near (i.e., within 0.5-1.5 km) an incinerator, 97 subjects who
lived far (i.e., within 3.5 km-4.0 km) from an incinerator, and 17 workers at a
new municipal solid-waste incinerator. The study commenced before the incinerator
started functioning in 1995, and 2 y later (1977) the authors undertook the final
part of the study. Dioxins, furans, and polychlorinated biphenyls were studied in
pooled blood samples (n = 22), and individual blood and urine samples were
analyzed for the detection of lead, chromium, cadmium, and mercury. In 1995,
dioxin blood levels were low-both among those living close to the incinerator
(mean = 13.5 ng international-dioxin toxic equivalents/kg fat) and among those
living far away (mean = 13.4 ng international-dioxin toxic equivalents/kg fat).
In 1997, dioxin and polychlorinated biphenyl levels had increased in both groups
of residents by approximately 25% and 12%, respectively. (The increase in dioxin
levels was about 10% when the authors took into account the mean of two repeated
quality-control analyses.) Blood lead levels decreased, but no difference was
observed for chromium, cadmium, and mercury. Minimal changes were seen among
workers. Given the low dioxin stack emissions from this plant (mean = 2.5-0.98 ng
international-dioxin toxic equivalents/m3) and that the blood dioxin levels did
not depend on distance of residence from the incinerator, it would appear
unlikely that the small increase in dioxin blood levels resulted from the
incinerator's emissions.
PMID- 11005432
TI - Study of the genotoxicity of toluene.
AB - Chromosome analysis was conducted for peripheral lymphocytes of 23 printers
exposed to toluene concentrations of 590 mg/m3 in a rotary machine workshop and
to rotogravure printing inks. The percentages of aberrant cells were 2.30 in the
printers and 1.46 in the control group (n = 22) (p < .05). The concentration of
hippuric acid in printers was significantly higher than in the control group (p <
.01), and the level of blood toluene at the end of the workshift was 0.500 mg/l.
The authors also examined rotogravure printing inks-considered a potential source
of genotoxic polycyclic aromatic hydrocarbons because they contained carbon black
their use in printing plants, and previous documentation of increased chromosomal
aberrations in rotogravure printers. Only milligrams of fluorene and phenanthrene
per gram of the printing inks were found; no polycyclic aromatic hydrocarbons
with carcinogenic properties were discovered in the inks. The authors used
Salmonella typhimurium indicator strains TA 98, TA 100, TA 1537, and YG 1041 in
spot tests and indicator strains TA 98 and TA 100 in plate-incorporation assays
to determine that there was no bacterial mutagenicity of all four colors of
rotogravure inks. Urinary mutagenicity, which was evaluated with a
microsuspension assay containing YG 1041 indicator strain both in the presence
and absence of metabolic activation, was also studied. No significant difference
in bacterial mutagenicity was found between the exposed and control groups. The
increased percentage of aberrant cells in printers can be explained by exposure
to genotoxicants that are not excreted in urine. Toluene was the most likely
cause of the aberration.
PMID- 11005433
TI - Concentrations of organochlorine pesticides in milk of Nicaraguan mothers.
AB - Breast-milk samples from 101 mothers from the basin of Rio Aloya, Nicaragua, were
collected on two occasions within the first trimester of lactation. Milk samples
were analyzed for 13 organochlorine pesticides: (1) p,p'
dichlorophenyldichloroethylene; (2) p,p'-dichlorophenyltrichloroethane; (3) p,p'
dichlorophenyldichlorodiene; (4) alpha-hexachlorocyclohexane; (5) beta
hexachlorocyclohexane; (6) gamma-hexachlorocyclohexane; (7) delta
hexachlorocyclohexane; (8) toxaphene; (9) dieldrin; (10) endrin; (11) aldrin;
(12) heptachlor; and (13) heptachlor-epoxide. Organochlorines of the
dichlorodiphenylethane class (i.e., p,p'-dichlorodiphenylethane and p,p'
dichlorodiphenylethane) were found in all samples and at the highest mean
concentrations observed in the study. Chemicals in the hexachlorocyclohexane
family (i.e., alpha- and delta-hexachlocyclohexane) were not found at all (0%),
and the other hexachlorocyclohexane compounds (i.e., beta > gamma) were found in
less than 6% of the samples. Twenty percent or less of the sample contained
chlorInated cyclodienes (i.e., dieldrin > endrin > heptachlor-epoxide >
heptachlor). No measurable concentrations of alpha-hexachlorocyclohexane, aldrin,
p,p'-dichlorophenyldichlorodiene, and toxaphene were found in the breast milk
samples. Analysis of variance demonstrated that only the concentration of p,p'
dichlorophenyldichloroethylene p,p'-dichlorophenyltrichloroethane, and endrin
were affected significantly by maternal age. Overall, with the exception of p,p'
chlorophenyldichloroethylene, and p,p'-dichlorophenyltrichloroethane, the mean
concentrations of the analyzed pesticides were low. Total p,p'
dichlorophenyltrichloroethane concentrations that exceeded the allowed daily
intake set by the World Health Organisation were found in 5.9% of the samples.
PMID- 11005434
TI - Effect of ventilation systems on prevalence of symptoms associated with "sick
buildings" in Brazilian commercial establishments.
AB - In this questionnaire study, the authors compared the prevalence of certain
symptoms and signs associated with Sick Building Syndrome and perceptions
relative to environmental discomfort of employees in a central-air-conditioned
dropping center and in natural-ventilation commercial shops located on the
streets of Niteroi, Rio de Janeiro, Brazil. There was a statistically significant
higher prevalence of symptoms (e.g., water and itching of eyes, sore throat, nose
irritation, difficulty breathing, skin irritation, sneezing) that were
characteristic of Sick Building Syndrome in the air-conditioned building than in
the naturally ventilated stores. The results indicated that there exists a
continuing need for further research in Brazilian work environments.
PMID- 11005435
TI - Mast cell disorder to be ruled out in MCS.
PMID- 11005436
TI - Arsenic body burden and morbidity and mortality.
PMID- 11005437
TI - Laparoscopic radical prostatectomy: feasibility studies or the future standard
technique?
PMID- 11005438
TI - Paediatric voiding dysfunction and enuresis.
AB - Urinary incontinence and nocturnal enuresis are frequently encountered problems
in children. In this review some aspects will be highlighted. Especially the
different types of monosymptomatic nocturnal enuresis as well as some recent
developments in children with dysfunctional voiding will be discussed.
PMID- 11005439
TI - Non-bacterial cystitis.
AB - The concept of non-bacterial cystitis (NBC) combines sterile urine and cystitic
symptoms as well as inflammatory changes, in particular in the mucosa and
submucosa of the bladder. It includes a multiplicity of vicious circles along the
entire continence reflex. An understanding of NBC presupposes knowledge of the
origin of the normal urinary urge and its successful control. Against the
background of the steadily increasing incidence of interstitial cystitis (often
irreversible end-stage NBC), it is suggested here that in the face of a failure
of first-line therapeutics (anticholinergics, cyclic antidepressants or
oestrogens), one must consider without delay the possible presence of NBC.
PMID- 11005440
TI - Urethral pathology.
AB - In the present review the eligible data on urethral pathologies are critically
analysed, with special attention given to unresolved controversies in this topic.
The entities discussed are as follows: female circumcision as a ritualistic
tradition, with many associated complications; prostatourethritis and urethral
syndrome; urethral diverticula as an overlooked rare pathology in urological
practice; urethrorectal fistula; pelvic fracture urethral injuries and its
current standard treatment algorithm; and urethral strictures and new endoscopic
or surgical reconstructive techniques.
PMID- 11005441
TI - Urinary diversion and reconstruction.
AB - Orthotopic bladder augmentation and substitution has been established as the
standard procedure for urinary diversion in many institutions, with current
studies reporting mainly on continence rates and procedure-associated
complications, such as the risk of impairment of neobladder function by local
tumor recurrences in the small pelvis. Similarly, in other types of continent
diversion, such as continent cutaneous diversion and rectal reservoirs, current
interest is primarily directed towards minimization of surgery-associated
complications.
PMID- 11005442
TI - Defining the biologic role of genes that regulate prostate cancer metastasis.
AB - Metastasis is the most lethal attribute of a cancer. There is a critical need for
markers that will accurately distinguish those histologic lesions and
disseminated cells that have a high probability of causing clinically important
metastatic disease from those cells that will remain indolent. Despite the
explosion in new information regarding the genetics of cancer, only six human
genes have thus far been shown to functionally suppress metastasis. The present
review and perspective describes the evolving view of the mechanisms that
regulate metastasis, and the importance of metastasis-suppressor genes in this
process. Specifically, the clinical problem of metastatic prostate cancer, the
identification of metastatic colonization as a therapeutic target, and the
identification and functional characterization of prostate cancer metastasis
suppressor genes are discussed.
PMID- 11005443
TI - The timing of hormonal treatment for prostate cancer.
AB - This article reviews publications investigating the optimal timing of androgen
ablative therapy for prostate cancer. We regard with some concern retrospective
series, the use of endpoints other than overall survival, the presentation of
actuarial and not actual survival, and the omission of appropriate controls.
Treatment of minimal residual disease and other clinical scenarios are explored.
PMID- 11005444
TI - Cryosurgery: is it an effective option for patients failing radiation?
AB - Cryotherapy of the prostate represents a potential treatment for localized
recurrent prostate cancer after radiation therapy. Current salvage cryotherapy of
the prostate can result in undetectable serum PSA levels with low morbidity.
Further refinements in technique and equipment may enhance cryosurgical results.
PMID- 11005445
TI - The effects of androgen deprivation on the prostate gland: cell death mediated by
vascular regression.
AB - Androgenic steroids are required to maintain the prostate gland in the adult
state. Consistent with this requirement, androgen deprivation therapies typically
induce a drastic regression of mature prostate tissue that is accompanied by the
extensive loss of prostate cells through the programmed cell death process
referred to as apoptosis. Whereas, in the past, the loss of prostate cells
associated with androgen deprivation has generally been perceived to be a direct
response of the androgen receptor-expressing prostate cells to an androgen
depleted environment, more recent studies of the prostate regression process
suggest that it might instead be initiated by an indirect response of the
prostatic parenchyma to an ischemic/hypoxic environment caused by a drastic
reduction of blood flow to the tissue that occurs when androgens are withdrawn.
This article reviews evidence that the prostatic vascular system is a primary
target of androgen action and other evidence suggesting that the regression of
the prostate parenchyma occurs secondarily to the regression of the prostate
vascular system through cell death mediated by tissue ischemia/hypoxia.
PMID- 11005446
TI - Imaging renal masses.
AB - Imaging plays a crucial role in the detection, characterization, and post
operative follow-up of renal masses. With rapidly advancing technology, imaging
techniques are continuously evolving. This review will discuss the current
modalities and techniques available for renal imaging, and recent developments.
PMID- 11005447
TI - Should radical nephrectomy be performed in the face of surgically incurable
disease?
AB - The role of cytoreductive nephrectomy in the management of metastatic renal
cancer remains controversial. Recent trials, like SWOG 8949 have suggested the
usefulness of this approach at least in selected patients with good performance
status and other favorable indicators. The timing of cytoreductive nephrectomy
has also been controversial and remains so to this time.
PMID- 11005448
TI - Immunotherapy: are we making a difference?
AB - There is a 10-20 year history of immunotherapeutic approaches in metastatic renal
cell cancer, which have produced a consistent demonstration of anti-tumour effect
in a small percentage of patients. Clarification of dose and schedule of current
agents continues to be modified. New technologies for immune system activation
are attempting to enhance the response rate and improve outcome. Anti
proliferative effects of immunotherapy produce prolongation of stable disease,
and new agents are being developed to enhance this approach.
PMID- 11005449
TI - Can biological markers predict recurrence and progression of superficial bladder
cancer?
AB - Biological markers that are predictive of recurrence and progression of
superficial bladder tumors must provide additional information to that provided
by multiplicity, size and grade. Field anomalies in normal appearing urothelium
of patients with papillary superficial transitional cell carcinoma have been
associated with tumor antigens and chromosome 9 deletions. Also, primary tumors
with chromosome 9 deletions are associated with a higher risk of recurrence.
Abnormal expression of p53, p21 and Ki-67 cell cycle markers have little
predictive value for recurrence. However, p53 overexpression or mutation and
decreased expression of p27 are associated with cancer progression and survival.
New markers, such as mutations in the fibroblast growth factor receptor 3 gene
(found in 30% of tumors), anomalies of the PTEN gene and vascular endothelial
growth factor expression, may have potential and require further evaluation.
Molecular fingerprints of superficial tumors with distinct clinical behavior are
being rapidly unravelled. Large-scale clinical studies are urgently needed to
provide supportive evidence for their incorporation in clinical management.
PMID- 11005450
TI - Management of superficial bladder cancer: what is new?
AB - The management of superficial bladder cancer has not changed much during the last
years. Transurethral resections with adjuvant intravesical instillation to risk
groups have been standard therapy. Cystoscopy and cytology have been used for
follow-up. Recently combinations of drugs for instillation and new urinary
markers for diagnosis and follow-up have been tested. The role of these new
modalities has not been easily judged. Thus the timely advent of guidelines with
policy recommendations will play an important part in improving the care of
patients in the future.
PMID- 11005451
TI - Advances in chemotherapy of invasive bladder cancer.
AB - A survey of the literature published during 1999 identified the following
advances in the chemotherapy of advanced bladder cancer. At present there are no
new chemotherapy regimens superior to MTX + VBL + ADR + CDDP (M-VAC), but
improvements in multidrug therapies and the development of new drugs suggest that
a new first-line chemotherapy will be established. The efficacy of neoadjuvant
chemotherapy could not be validated by meta-analysis, but neoadjuvant
chemotherapy can be expected to be a useful tool for individualizing therapy. If
it was possible to select accurately those patients who show complete response to
a certain chemotherapy regimen, then this selected group would show a 100%
complete response rate on that regimen, regardless of the complete response rate
of this regimen in an unselected population. Such individualization of therapy
would aid in future establishment of bladder-preserving treatment methods for
invasive bladder cancers.
PMID- 11005452
TI - Outcome of radical cystectomy for invasive bladder cancer.
AB - Even though radical cystectomy still remains the 'gold standard' for the
treatment of invasive bladder cancer, newer insights and developments are
entering the urological arena: a 'tailored' surgical approach combining a less
extensive procedure and a better quality of life seems feasible for selected
patients without compromising the outcome; the type of urinary diversion has no
impact on the risk of complications, the ability to receive postoperative salvage
treatments and the natural history of the disease; the depth of extension of the
tumour and the nodal involvement are the only independent 'classical' predictors
of survival after radical cystectomy; pelvic node dissection is curative in
patients with limited nodal involvement; the clinical application of newer
molecular prognostic factors still remains controversial.
PMID- 11005453
TI - Prognostic parameters for the management of advanced testis tumours.
AB - The need for prognostic parameters in testicular germ cell tumours is sometimes
questioned based on an overall cure rate of more than 80% of the patients
regardless of tumour stage. However, the trend for an earlier and more accurate
diagnosis amenable to curative treatment as well as the high effectiveness of
standard Cisplatinum containing chemotherapy has masked the continuing need for
intensifying therapy in patients with adverse risk factors. This intense
treatment is often associated with worrysome morbidity and the assessment of
prognostic factors, stage by stage, is warranted on which patient at risk can be
identified and treated accordingly. Traditional prognostic factors, on which most
classification systems are based, include large tumour volume, the presence of
liver, bone or brain metastasis, grossly elevated tumour markers and an
extragonadal primary site, particularly in the mediastinum. Novel prognostic
factors are either (1) independent from the patient and his disease, (2) inherent
on the patient's characteristics or (3) based on tumour biology. Clearly, the
infrastructure and the experience of the treating uro-oncology unit (see 1) is
decisive for treatment outcomes, and -at least-'difficult to treat' patients
should be referred to properly resourced cancer centres. Patients with higher
socio-economic status, willing to travel and well educated enough to be worried
about their diseases status apparently gain access to expert centres more easily
(see 2), translating into an upgrade on prognosis. Finally, biologic factors (see
3) such as beta-human chorionic gonadotrophin or MAGE epitopes in seminoma or the
percentage of embryonal carcinoma components orvascular invasion mayor may not
inversely influence the prognosis and need further assessment in prospective
trials. However, the search for even better (molecular) biologic factors is
speeding up because more complex treatment decisions such as in advanced
testicular cancers rely on a more precise determination of prognosis, enabling a
more tailored selection of individualized therapeutic options.
PMID- 11005454
TI - Sexual function and fertility after treatment of testicular cancer.
AB - As a result of the introduction of effective cisplatin-based chemotherapeutic
regimens into the clinical routine, even patients with metastatic testicular
cancer at initial diagnosis can be cured of their disease. Sexual dysfunction and
infertility are common long-lasting sequelae in testicular cancer survivors,
affecting approximately 20% of patients after the application of the different
treatment modalities currently available for the treatment of early and advanced
clinical stages, including retroperitoneal surgery and systemic chemotherapy.
Accordingly, it has been demonstrated that fertility distress and sexual
disturbances, the latter occurring in only a minority of patients after surgical
or chemotherapeutic treatment of testicular germ cell tumours, substantially
alter the patients' quality of life. It is even worse because testicular cancer
mostly affects men in the prime of their physical, sexual and reproductive
function. Although semen quality is frequently poor at initial diagnosis and
further deteriorates after orchiectomy, probably because of structural
abnormalities in the remaining contralateral testicle, the advent of
intracytoplasmatic sperm injection promises a fertile future to most patients,
even if only a few sperms are present in the ejaculate. Further long-term
investigations should be initiated to clarify the impact of the different
treatment modalities on fertility and sexual life. The main objective should be
the identification of patients who are at increased risk of developing therapy
related physical and psychological problems.
PMID- 11005455
TI - Bibliography. Current world literature. Voiding dysfunction and female urology.
PMID- 11005456
TI - Bibliography. Current world literature. Oncology: prostate and renal.
PMID- 11005457
TI - Bibliography. Current world literature. Oncology: bladder and testis.
PMID- 11005458
TI - Overview: pulmonary thromboembolism.
PMID- 11005459
TI - Incidence of pulmonary embolism: is it declining?
AB - Several factors make analysis of time trends in the incidence of pulmonary
embolism difficult. Apart from the methodologic problems, a number of factors
could explain an increasing as well as a decreasing incidence. The few studies on
pulmonary embolism discovered after death are discussed, and the evidence shows a
decrease in incidence, especially after the mid 1970s. This can be explained by
many factors, of which the 2 most important are the increased use of
thromboprophylaxis and better treatment of established deep vein thrombosis.
PMID- 11005460
TI - Current status of pulmonary embolism and venous thrombosis prophylaxis.
AB - Prophylaxis for venous thromboembolism is an area that has received intense study
in certain conditions, but less than adequate coverage in other areas. In
considering who needs prophylaxis, patients are categorized into levels of risk.
Clinical venous thromboembolism can be correlated to these levels of risk.
Methods of prophylaxis include pharmacologic, mechanical, and combinations of
these. Each category of surgical and medical patient requires specific types of
prophylaxis. In certain orthopedic indications, the length of prophylaxis
outlasts the inpatient hospital stay and may be as long as 1 month after
discharge. Even with the best prophylaxis today, the incidence of deep venous
thrombosis (DVT) and pulmonary embolism (PE) is decreased by only approximately
70% to 80%. Further developments should allow for greater declines in the rates
of venous thromboembolism, with its subsequent short-term consequence of
pulmonary embolism and lower extremity morbidity and long-term consequence of the
disabling syndrome of chronic venous insufficiency (CVI).
PMID- 11005461
TI - Current diagnostic techniques for pulmonary embolism.
AB - The diagnosis of venous thromboembolism (VTE) includes deep venous thrombosis
(DVT) and pulmonary embolism (PE) and requires objective testing. The clinician
uses a combination of risk factors and nonspecific clinical findings to identify
patients who warrant such an evaluation. The recommended approach begins with
ventilation/perfusion (V/Q) lung scans or lower extremity noninvasive studies by
compression ultrasonography. Nondiagnostic V/Q scans or negative noninvasive
studies require further testing. A high-probability V/Q scan or a positive
noninvasive study warrant treatment. A normal V/Q scan excludes the diagnosis of
PE. Helical computed tomography (CT) can diagnose PE of major vessels but is not
sufficiently sensitive to exclude PE because of its poor sensitivity for
subsegmental pulmonary vessels. Newer D-dimer assays have a high negative
predictive value, but results vary with the specific assay and do not perform
well in patients with cancer. Future studies are needed to validate magnetic
resonance imaging (MRI) or magnetic resonance angiography (MRA).
PMID- 11005462
TI - Low-molecular-weight heparin in the treatment of pulmonary embolism.
AB - Unfractionated heparin is the traditional treatment of choice for patients
presenting with submassive pulmonary embolism. However, newer low-molecular
weight heparins have been developed and tested in several clinical trials in the
last 2 decades because of the many limitations of unfractionated heparin. The
pharmacologic properties of the low-molecular-weight heparins allow them to be
administered subcutaneously in fixed, weight-adjusted doses without need for
laboratory monitoring. Different studies have recently proved their efficacy in
the treatment of patients with deep vein thrombosis. Because there is good
evidence that deep vein thrombosis and pulmonary embolism are 2 expressions of a
single disease, the use of low-molecular-weight heparins has been extended to
patients presenting with clinically stable pulmonary embolism. In particular, the
results of 2 important clinical trials, the Columbus and the Thesee, have
conclusively proved that the low-molecular-weight heparins are as safe and
effective as unfractionated heparin. In some centers, approximately 80% of
patients with deep vein thrombosis are treated at home. This suggests that
carefully selected patients with clinically stable pulmonary embolism can receive
home treatment with low-molecular-weight heparins.
PMID- 11005463
TI - Indications for filter placement.
AB - Indications for placement of a vena caval filter reflect the perception of
efficacy and safety of these devices. The traditional indications include
contraindications to or complications of anticoagulation. Over time, physicians
have expanded these indications to include prophylactic placement in patients at
high risk of pulmonary embolism. The decision to place a filter should be made
only after weighing the risks and benefit in each situation. Long-term outcomes
should be carefully evaluated.
PMID- 11005464
TI - Filter placement by ultrasound technique at the bedside.
AB - Vena cava filtration devices are commonly inserted for the prevention of fatal
pulmonary emboli. Several imaging methods are used today to direct device
placement. Bedside insertion has several advantages, particularly in the
critically ill patient. Imaging techniques include bedside fluoroscopy,
transperitoneal ultrasound, and intravascular ultrasound. We have now
successfully placed 10 transfemoral vena cava filters by use of intravascular
ultrasound at the patient's bedside. This appears to be a feasible method for
filter insertion.
PMID- 11005465
TI - Current vena cava filter devices and results.
AB - The critical focus in the acute management of deep vein thrombosis (DVT)
continues to be the effective prevention of associated life-threatening pulmonary
embolism (PE) and the achievement of survival for those in whom such emboli
occur. As such, primary treatment for DVT or PE demands adequate anticoagulation
with intravenous heparin followed by maintenance oral warfarin for 3 to 6 months.
This centered approach successfully prevents 90% to 95% of cases of associated
pulmonary embolism. However, under circumstances in which anticoagulation cannot
be used, or in which it fails, there is clear indication for placement of a
mechanical filter into the inferior vena cava to provide a protective barrier
against the passage of clinically significant emboli from pelvic or lower
extremity veins. Considerable technical ingenuity and continued evolution of
materials and design have propelled the development and number of vena cava
filters available for clinical use. Variable data on safety and effectiveness
require physicians to match the best filter to each patient's particular
situation and anatomy. However, many interventional radiologists and surgeons
often base their filter selection on ease of insertion and device cost. Thus, it
is paramount that physician users of these devices remember that the primary
objective of vena cava filtration is to provide a safe and effective device for
permanent implantation. If this objective is not met, the quality of care in the
management of deep venous thrombosis or pulmonary embolism will diminish.
PMID- 11005466
TI - Filter complications and their management.
AB - Complications from the use of vena caval filters are rare but can occur at
placement, during other procedures, or late in follow-up. Placement problems such
as bleeding from the insertion site or embolism from thrombus manipulation are
largely avoidable. Technical difficulties with introduction, positioning, or
misplacement have been minimized by use of flexible carriers and guidewires.
However, later insertion of guidewires without fluoroscopy for line changes can
lead to problems of entrapment. Filter capture of emboli can result in further
thrombus propagation at that site or in filter obstruction. Management of these
events requires adequate visualization to determine whether to use lytic therapy
or a second filter. Late complications include filter strut fracture in 0.05% of
cases and filter penetration, of even rarer functional significance. Pain that
can be attributed to the filter has been found only in a single case of pelvic
misplacement. The limited consequences of mechanical changes in the filter argue
strongly against unnecessary interventions, which frequently result in an
increase in morbidity.
PMID- 11005467
TI - The current role of thrombolytic therapy for pulmonary embolism.
AB - Thrombolytic therapy for pulmonary embolism can rapidly reverse right ventricular
failure and reduce mortality and morbidity among appropriately selected patients.
Individuals being considered for this treatment should be screened for potential
major bleeding problems, which, if present, should lead to alternative management
with catheter or surgical embolectomy. There is no ideal thrombolytic agent; nor
have indications for thrombolysis been precisely defined. Available data indicate
that patients with moderate or severe right ventricular dysfunction gain the most
from this pharmacologic strategy.
PMID- 11005468
TI - Catheter technique for pulmonary embolectomy or thrombofragmentation.
AB - The management of acute massive pulmonary embolism (PE) constitutes a major
clinical problem because of the associated derangement of hemodynamic and
respiratory functions from obstruction to pulmonary blood flow. Despite advances
in management with thrombolytic therapy or open embolectomy, the mortality rate
remains high. To improve the chance of survival, catheter techniques that are
capable of removing or fragmenting the clot have been developed. These include
catheter pulmonary embolectomy and thrombofragmentation. The former involves the
introduction of a suction catheter from a femoral or jugular venotomy through the
right heart into the appropriate pulmonary artery under fluoroscopic guidance.
The technique for the latter involves the percutaneous introduction of a
fragmentation catheter from a femoral vein through a guiding catheter into the
appropriate pulmonary artery. The success of the catheter technique in removing
pulmonary emboli varies with different devices. The overall success rate is
approximately 76%, with a mortality rate of 25%. Transvenous pulmonary
embolectomy and thrombofragmentation are safe and effective techniques for
treating patients with massive PE. The success of each of the techniques depends
on a thorough understanding of the mechanism of action of each of the devices
used and a facile catheterization technique.
PMID- 11005469
TI - Indications for and the results of pulmonary thromboendarterectomy for
thromboembolic pulmonary hypertension.
AB - Most episodes of acute pulmonary embolism completely resolve, through
thrombolytic mechanisms. When adequate thrombolysis fails, however, residual
obstruction to pulmonary vascular flow by fibrotic remnants may result in
pulmonary hypertension. The genesis of this pulmonary hypertension is complex.
Apart from the simple mechanical obstruction to blood flow that may occur from
occlusion of significant areas of the pulmonary vascular bed, secondary vascular
changes eventually may result from increased flow and pressure in nonobstructed
areas of the lung, or factors generated by localized hypoxia in occluded
segments. Chronic pulmonary hypertension from thromboembolism, regardless of the
mechanism, is much more prevalent than is generally appreciated. Patients develop
increasing shortness of breath, and the diagnosis is often missed. Pulmonary
endarterectomy offers a cure for the condition, and wider recognition of the
efficacy of the operation and the entity are therefore important. Pulmonary
endarterectomy is a technically demanding procedure, now performed with success
at only a handful of centers. However, with proper patient selection, meticulous
surgical technique, and careful postoperative management, excellent results can
be obtained. A true endarterectomy (not an embolectomy) of all affected parts of
the lung is performed, and cardiopulmonary bypass, systemic cooling, and
circulatory arrest are essential for the visibility necessary to clear all
affected areas of the pulmonary vasculature. Medical treatment is ineffective for
this condition, and the alternative surgical treatment is lung transplantation.
Pulmonary endarterectomy appears to be permanently curative, though an inferior
vena caval filter should be placed in all patients to prevent recurrence, and the
patients must have life-long anticoagulation.
PMID- 11005470
TI - Transvaginal approach to Cooper's ligament during incontinence surgery.
PMID- 11005471
TI - Intraurethral ultrasonography: correlation of urethral anatomy with functional
urodynamic parameters in stress incontinent women.
AB - To determine whether differences in functional urodynamic parameters can be
explained by changes in urethral anatomy, 39 patients underwent intraurethral
ultrasonography to obtain a 360 degree view of the urethra. The point of maximal
rhabdosphincter thickness was identified in all patients. The thickness,
circumference and area of the urethral smooth and skeletal muscle layers were
calculated. Data from patient histories and urodynamic evaluations were compared
with this anatomical survey. The urodynamic diagnoses were as follows: 10
patients were normal, 24 had genuine stress incontinence and 5 had intrinsic
sphincter deficiency. These patients had decreasing rhabdosphincter thicknesses
of 3.91, 3.35 and 2.70 mm (P = 0.048). A weak linear relationship was found
between maximal urethral closure pressure and rhabdosphincter (r = 0.40, P =
0.013) and longitudinal smooth muscle (r = 0.35, P=0.027) thickness. It was
concluded that a loss of urethral resistance as measured by maximal urethral
closure pressure is associated with changes in urethral anatomy identified by
intraurethral ultrasonography.
PMID- 11005472
TI - Pelvic muscle exercise effect on pelvic muscle performance in women.
AB - The aim of this study was to compare pelvic muscle (PM) characteristics
(strength, endurance and contractability) before and after 12 weeks of pelvic
muscle exercises in two groups of older women: the first composed of women with
genuine stress incontinence, and the second made up of women with no symptoms of
urinary incontinence or pelvic organ prolapse. This research also investigated
the extent to which PM pressure and health-related characteristics could help
discriminate between women with and without a clinical sign of PM dysfunction.
Within a framework of skeletal muscle fitness, outcome measures were defined and
compared. There was no significant difference in the baseline (P = 0.09) and post
PME (P = 0.63) strength, endurance and contractability of the two groups of
women. The two groups did differ significantly on change scores (P = 0.05)
following PME. A greater improvement in strength for women without a clinical
sign of dysfunction was demonstrated. There was a probability of 91% that those
with a history of gynecological surgery belonged to the group of women with SUI.
PMID- 11005473
TI - Bacterial vaginosis increases in pessary users.
AB - The purpose of this study was to examine the association between pessary use,
smoking and changes in the vaginal flora. Patients using pessaries were age
matched with non-pessary using controls. All candidates examined were women
attending the Mount Sinai Hospital, Toronto, for genitourinary problems. Vaginal
cultures were routinely performed on all women attending the unit, irrespective
of symptoms. Forty-four pessary users were age matched with 176 controls (4
controls per case). The mean age was 60.1 +/- 12.6 years, and 15% of these were
premenopausal. The duration of pessary use ranged from 0.5 to 8 years (mean 3.3
+/- 1.7). Weight, parity, smoking status, diabetes mellitus, thyroid disease, UTI
and postvoid residual urine volume were not significantly different between
pessary users and controls. Bacterial vaginosis (BV) was noted in 32% of pessary
users, versus 10% of controls. The relative risk of developing BV in pessary
users was 3.3 (OR, 4.37; 95% CI, 2.15-9.32), P = 0.0002. Smoking independently
affected the vaginal flora, increasing the relative risk of developing BV to 2.9
(OR, 3.78; 95% CI, 2.05-8.25), P = 0.0013. It was concluded that pessary use is a
very effective and conservative method for the treatment of genital prolapse.
However, we found that the presence of a foreign body was associated with changes
in the vaginal flora, thereby increasing the odds of developing bacterial
vaginosis to 4.37; this was further compounded by smoking.
PMID- 11005474
TI - Orthotopic ileal neobladder in females: impact of the urethral resection line on
functional results.
AB - We present our functional experience with orthotopic bladder replacement in
female patients dependent on the urethral resection line. Between November 1986
and July 1998 42 women underwent orthotopic urinary tract reconstruction with an
ileal neobladder at our institution: 26 patients underwent radical cystectomy
(RCx) with subsequent ileal anastomosis to the urethra, and 16 underwent simple
cystectomy (SCx) with preservation of the bladder neck. Fourteen of 22 patients
following RCx and 3 of 14 patients following bladder neck-sparing cystectomy void
naturally. Clean intermittent catheterization is necessary in 8 of 22 and 11 of
14 patients, respectively. Perfect continence with no pads at 1 year
postoperatively was achieved in 15 of 18 evaluable patients following RCx and 10
of 11 patients following bladder neck sparing. Incontinence requiring one or more
pads is present in 3 of 18 patients and 1 of 11 patients, respectively.
Subjectively satisfactory continence was achieved in 16 of 18 patients following
RCx and in all patients following bladder neck-sparing surgery. Our conclusions
are that radical cystectomy as well as a bladder neck-sparing cystectomy does
provide satisfactory functional results in the majority of patients. However, the
urethral resection line does slightly influence the rate of incontinence as well
as the requirement for intermittent catheterization. RCx does translate into a
lesser requirement for CIC, whereas bladder neck sparing results in slightly
better continence rates.
PMID- 11005475
TI - Patient satisfaction and complications following sacral nerve stimulation for
urinary retention, urge incontinence and perineal pain: a multicenter evaluation.
AB - The aim of the study was to determine the success rate, the complications, the
failures and the solutions found in troublesome cases. A retrospective study was
performed in three university centers in Belgium. Between March 1994 and April
1998, a quadripolar electrode and a pulse generator were implanted in 53 patients
(8 men, 45 women, 43 +/- 12 years, mean follow-up 24 +/- 8 months, range 13-39
months). During the first few months, 45 (85%) of the 53 patients had an
objective response. Eight late failures occurred, with a mean failure delay of 9
+/- 5 months. We performed 15 revisions in 12 patients. Major complications were
pain and current-related troubles. The outcome was significantly better (P =
0.001) in post-stress incontinence surgery patients. Device-related pain was
found more frequently in patients with dysuria and/or retention or perineal pain,
and the test stimulation was less reliable (P = 0.025) in patients with a
psychiatric history. Sacral nerve stimulation is efficient in treating patients
with refractory lower urinary tract symptoms and/or perineal pain.
PMID- 11005476
TI - 'Nerve-sparing' cystectomy in women.
AB - Although the indications for cystectomy other than for cancer are few, it is
occasionally necessary for severe interstitial cystitis or hemorrhage due to
radiation cystitis. The use of substitution cystoplasty after cystectomy has
increased in men in the last decade, and this has resulted in the development of
'nerve-sparing' approach to cystectomy to improve continence and potency. The use
of substitution cystoplasty in women after cystectomy has lagged behind that in
men because it was considered necessary to remove the entire urethra, making
orthotopic substitution impossible. Recently the need to remove the entire
urethra has been questioned, with the finding that if the bladder neck is free of
tumour, recurrence of disease in the urethra has not so far been found to occur.
In addition, it appears possible to substitute on to the urethra without
incontinence. This has led to the development of a 'nerve-sparing' technique of
cystectomy, and renewed interest in the anatomy of the urethra. This paper
reviews the current literature on 'nerve-sparing' cystectomy and describes our
technique.
PMID- 11005477
TI - Posthysterectomy vault prolapse.
AB - The incidence of vault prolapse is uncertain but appears to be increased five
fold after vaginal hysterectomy. A precise scoring system has now been devised to
overcome the diagnosis and classification of this condition. Conservative
measures may be used to treat this condition in women unfit for surgery or those
who require symptomatic relief while awaiting surgery. The surgical options lie
between a vaginal sacrospinous fixation, or abdominal procedures such as
sacrocolpopexy or vault suspension operations. The success rate for these
operations is over 90%. Pre-operative urodynamic evaluation is mandatory since
these patients frequently have concomitant stress urinary incontinence which may
require correction at the same time. The choice of operation will undoubtedly
depend upon the experience of the surgeon but greater awareness and alteration of
technique at the time of the original hysterectomy may be the better solution to
reducing the incidence of vault prolapse.
PMID- 11005478
TI - Bladder substitution in women.
AB - Although numbers are still small and follow-up is often limited, female
orthotopic bladder reconstruction has been shown to provide excellent, near
normal voiding and storage function in selected patients, and its popularity has
been growing over the last decade. The true role of this form of surgery,
however, is not yet fully established. This paper discusses the indications for
patient selection, operative technique and outcome of female bladder
substitution. Outcome is equivalent to that seen in male patients, although in
some series there is a higher rate of voiding dysfunction requiring intermittent
self-catheterization. Although further data regarding urethral recurrence rates
are awaited, it would seem that with careful patient selection and operative
technique, cancer surgery may not be compromised. Functional results have been
excellent and patient satisfaction is very high. Provided there is a functional
external sphincter and tumor margins can be safely cleared, this form of surgery
offers patients the best opportunity to preserve quality of life following
cystectomy.
PMID- 11005479
TI - Urodynamic assessment of voiding dysfunction and dysfunctional voiding in girls
and women.
AB - Voiding dysfunction is defined as impaired bladder emptying, and presents with a
mixture of lower urinary tract symptoms. Dysfunctional voiding is a condition in
which there is a lack of coordination between the sphincter and detrusor during
emptying in a patient without overt uropathy or neuropathy. Assessment of voiding
dysfunction is important in women and girls in the prevention and treatment of
urinary incontinence, retention, urinary tract infection and subsequent kidney
damage. Accurate diagnosis is essential in order to select the correct treatment.
Screening can be done by history-taking: symptom scores can help to guide the
screening. More objective measures are uroflowmetry, ultrasonography and video
urodynamics. The latter is the gold standard for the diagnosis of voiding
dysfunction and consists of simultaneous registration of pressure in the bladder
and rectum and external sphincter behavior, either by electromyographic recording
of pelvic floor activity or by pressure recording at the external sphincter,
during the whole bladder cycle of filling and emptying. On fluoroscopy the
bladder can be visualized throughout the filling and emptying phase. In
dysfunctional voiding, hypertonicity and instability of the external urethral
sphincter during filling cystometry and impaired external sphincter relaxation
during emptying are pathognomonic findings. Pressure-flow analysis reveals no
obstruction and the detrusor contractility is low.
PMID- 11005480
TI - The use of mesh in gynecologic surgery.
PMID- 11005481
TI - Practice parameters for antibiotic prophylaxis to prevent infective endocarditis
or infected prosthesis during colon and rectal endoscopy. The Standards Task
Force. The American Society of Colon and Rectal Surgeons.
PMID- 11005483
TI - A bold message for the next millennium.
PMID- 11005482
TI - Practice parameters for antibiotic prophylaxis--supporting documentation. The
Standards Task Force. The American Society of Colon and Rectal Surgeons.
PMID- 11005484
TI - Patient satisfaction after surgical treatment for fistula-in-ano.
AB - PURPOSE: The surgical treatment of fistula-in-ano frequently results in
recurrence of the fistula or postoperative anal incontinence. Despite these
problems, most patients are satisfied with the results of their surgery. To
clarify this apparent discrepancy, we attempted to identify factors that affect
patient's lifestyles and may contribute to their satisfaction. METHODS: A
questionnaire was mailed to 624 patients surgically treated for cryptoglandular
fistula-in-ano at the University of Minnesota during a five-year period. Three
hundred seventy-five patients returned their questionnaires. Patients who were
followed up for a minimum of one year were included in this retrospective study.
Associations between postoperative complications and patient satisfaction were
identified by chi-squared tests and multiple logistic regression. Attributable
fractions for patient dissatisfaction were calculated using study population
dissatisfaction rates. RESULTS: Patient satisfaction was strongly associated with
fistula recurrence, difficulty holding gas, soiling of undergarment, and
accidental bowel movements. Effects of incontinence on patient quality of life
were also significantly associated with patient satisfaction as was the number of
lifestyle activities affected by incontinence. Patients with fistula recurrence
reported a higher dissatisfaction rate (61 percent) than did patients with anal
incontinence (24 percent), but the attributable fraction of dissatisfaction for
incontinence (84 percent) was greater than that for fistula recurrence (33
percent). Patient satisfaction was not significantly associated with age, gender,
history of previous fistula surgery, type of fistula, surgical procedure, time
since surgery, or operating surgeon. CONCLUSION: Patient satisfaction after
surgical treatment for fistula-in-ano is associated with recurrence of the
fistula, the development of anal incontinence, and with the effects of anal
incontinence on patient lifestyle. In our series of patients treated mainly with
laying open of the fistula tract, patients with fistula recurrence had a higher
dissatisfaction rate than did patients with anal incontinence. However, because
anal incontinence was more prevalent than fistula recurrence, a higher fraction
of dissatisfaction was attributable to anal incontinence.
PMID- 11005485
TI - Restoring control: the Acticon Neosphincter artificial bowel sphincter in the
treatment of anal incontinence.
AB - PURPOSE: Anal incontinence is a socially disabling problem affecting 1 to 2
percent of the population. Anal sphincter replacement is a treatment option if
the problem is severe and not amenable to direct repair. The artificial bowel
sphincter is an innovative approach. We report the technique for placement and
the outcomes which have occurred in an initial series of 13 patients. METHODS:
The Acticon Neosphincter artificial bowel sphincter consists of an inflatable
cuff of silicone elastomer placed around the anal canal and connected to a
pressure-regulating balloon in the iliac fossa via a control pump placed in the
labium or scrotum. Thirteen patients with severe anal incontinence not amenable
to other methods were treated. Causes of incontinence included obstetric damage
in eight patients, surgical damage in two patients, imperforate anus in two
patients, and spina bifida in one patient. RESULTS: Surgical placement of the
device was straightforward, mean operating time was 65 minutes, and median length
of stay was 3.6 days. One infection of the perineal wound occurred in the early
postoperative period necessitating removal of the device. In two further patients
the artificial bowel sphincter was removed because of late infection in one at
seven months and because of erosion through the skin in another at three months.
The artificial bowel sphincter has been activated in ten patients resulting in
full continence to solids and liquids except in one patient with postvagotomy
diarrhea who had some leakage of liquids during episodes of diarrhea. The mean
(+/- standard deviation) continence score (Cleveland Clinic system; maximal
incontinence = 20) changed from 18.7 +/- 1.6 preoperatively to 2.1 +/- 2.6 after
activation (P < 0.0001). Quality of life measured using a continence-specific
series of up to 39 questions changed from 77 +/- 16 percent of maximal reduction
of quality preoperatively to 12 +/- 19 percent postoperatively (P < 0.001).
CONCLUSIONS: The artificial bowel sphincter can be placed without technical
difficulty and with low morbidity. Preliminary experience shows full restoration
of continence in most patients and ease of use. Longer follow-up is needed to
determine the extent of problems with infection, erosion, and mechanical failure.
PMID- 11005486
TI - Outcome of patients with rectal adenocarcinoma and localized pelvic non-nodal
metastatic foci.
AB - PURPOSE: The aim of this study was to evaluate the outcome of patients with
primary rectal adenocarcinoma and soft tissue metastatic foci restricted to the
pelvis and to determine whether this entity, which is considered N1 disease in
the American Joint Committee on Cancer staging system, behaves like completely
replaced nodal disease or the first sign of M1 disease. The clinical course for
patients with this finding is not well-described in the literature. METHODS: The
authors retrospectively reviewed the medical records of 395 patients with rectal
adenocarcinoma who received radiation treatment. Eighteen patients had pelvic
soft tissue metastatic foci. Exclusions from this study included 1) cases without
metastatic pelvic foci; 2) cases of recurrent cancer; 3) cases with known distant
metastatic disease as defined by American Joint Committee on Cancer criteria; and
4) cases with extrapelvic metastatic foci. All patients received adjuvant
radiotherapy. Thirteen cases received preoperative radiotherapy. Four cases
received postoperative radiotherapy. One case received both preoperative and
postoperative radiotherapy. Eight cases received chemotherapy. RESULTS: All
eighteen patients had T3 or T4 lesions. Thirteen patients had lymph nodes that
contained metastatic disease and would therefore have been scored N1 or N2 even
without the pelvic tumor implants. Sixteen of 18 (89 percent) patients died of
disease after a survival time of 12 to 37 (mean, 25) months. Only 1 of 18 (6
percent) patients was disease free at five years. The other remaining survivor
was undergoing palliative therapy for metastatic disease to the lung. This is
significantly worse than our institution's experience with T3,4N+ disease after
preoperative radiation (5-year survival, 11 vs. 56 percent; P = 0.0002,
Generalized Wilcoxon of Breslow). There was a high incidence of local (9/18) and
distant (14/18) failure. No other factor, including radiation dose, margin
status, chemotherapy, T stage, and number of involved nodes or soft tissue
implants, correlated independently with outcome. CONCLUSIONS: Pelvic metastatic
foci confer a significantly worse prognosis than other T3,4N+ disease. Such cases
should be excluded from prospective trials for localized disease. Although this
entity probably represents M1 disease for most patients, survival can be long,
and aggressive locoregional and systemic treatment is warranted.
PMID- 11005487
TI - Colorectal cancer before the age of 40: a case-control study.
AB - PURPOSE: Colorectal adenocarcinoma before the age of 40 is uncommon, and its
prognosis is controversial, with many studies reporting a worse prognosis than in
older patients and others showing no difference. The current study compared two
groups of patients who had surgical resection for colorectal adenocarcinoma.
METHODS: The case group was composed of 34 patients younger than 40 (34 +/- 4)
years. Detailed pathologic prognosis factors, tumor cell proliferation measured
by proliferating cell nuclear antigen, survival, family history, and predisposing
conditions were analyzed. Results were compared with a control group constituted
of 34 patients older than 65 (75 +/- 6) years matched by gender, cancer site, and
Dukes stage. RESULTS: Tumor differentiation, presence of vascular and perineural
neoplastic invasion, tumor growth pattern, tumor cell proliferation measured by
proliferating cell nuclear antigen count, and survival according to the Kaplan
Meier method were not significantly different between younger and older patients.
The only difference between the two groups was a higher prevalence of family
history and predisposing conditions for colorectal cancer in younger patients (23
vs. 3 percent; P = 0.03). CONCLUSION: This case-control study documents that
pathologic features and prognosis of colorectal adenocarcinoma are comparable in
patients younger than 40 years compared with older patients for identical stages.
The higher prevalence of positive family history in younger patients suggests a
different genetic background compared with older patients.
PMID- 11005488
TI - Apoptosis in rectal cancer: prognostic significance in comparison with clinical
histopathologic, and immunohistochemical variables.
AB - PURPOSE: The aim of this study was to evaluate the prognostic value of the
apoptotic index for recurrence and disease-free survival after curative surgery
for rectal cancer, particularly in relation to clinicopathologic variables, p53-
and bcl-2 expression. METHODS: Formalin-fixed, paraffin-embedded tissue samples
of rectal carcinomas resected curatively within a five-year period were used (N =
160). Apoptotic cells with fragmented DNA were detected by the terminal
deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase-biotin nick-end
labeling method. The ratio of apoptotic tumor cells (in percent) was classified
into low apoptotic index (less than 10 percent) and high apoptotic index (10
percent or more). Immunohistochemical analysis was performed using monoclonal
antibodies (DO-1 for p53 and clone 124 for bcl-2). Statistics included univariate
and multivariate analysis, and survival was calculated using the Kaplan-Meier
method. RESULTS: Seventy-five percent of tumors showed a low apoptotic index, and
25 percent had a high apoptotic index. No correlation was found between apoptotic
index and International Union Against Cancer stage (P > 0.05). However,
significant correlations were documented with histologic differentiation (mean
apoptotic index, 5.74 percent in moderately vs. 3.98 percent in poorly
differentiated carcinomas; P = 0.0173), lymph node involvement (mean apoptotic
index, 6.11 percent in pN1 vs. 3.72 percent in pN2; P = 0.0074), p53 status (mean
apoptotic index, 6.26 percent in p53- vs. 4.42 percent in p53+; P = 0.0085), and
bcl-2 expression (mean apoptotic index, 5.13 percent in bcl-2- vs. 6.51 percent
in bcl-2+; P = 0.0418). Tumors of the lower rectum had a lower apoptotic index
than those of the upper rectum (P = 0.0277). Neither univariate nor multivariate
analysis assessed apoptotic index as predictor of prognosis: Recurrence rates did
not differ between tumors related to apoptotic index (22 percent with low
apoptotic index vs. 15 percent with high apoptotic index; P > 0.05), and no
significant differences were found regarding survival (P > 0.05). On multivariate
analysis, International Union Against Cancer stage (P = 0.0002), p53 (P =
0.0002), gender (P = 0.0136), and bcl-2 (P = 0.0243) were independent predictors
of recurrence. These variables, except for bcl-2, were also independently related
to disease-free survival. CONCLUSIONS: Reflecting tumor biology, apoptotic index
as single variable showed no prognostic significance, whereas p53 was an
independent predictor for both recurrence and survival, and bcl-2 was
independently related to recurrence, but not to survival. Clinically,
International Union Against Cancer stage and gender were independent prognostic
factors after curative surgery for rectal cancer.
PMID- 11005489
TI - Selective total mesorectal excision for rectal cancer.
AB - PURPOSE: Total mesorectal excision has been advocated for rectal cancer, but its
use in upper rectal and rectosigmoid tumors remains a point of debate. METHODS:
One hundred seventeen patients with rectal cancers were subjected to a
prospective policy of total mesorectal excision for mid and low rectal cancers
and a wide (5 cm) distal margin mesorectal excision for upper rectal and
rectosigmoid cancers. RESULTS: Forty-one patients underwent ultralow anterior
resection, 10 underwent abdominoperineal excision, 64 had anterior resection and
2 had Hartmann's procedure. The median follow-up was 39 months. Forty-three
patients had a defunctioning ileostomy. Three patients (7.3 percent) had
anastomotic leaks after ultralow anterior resection with total mesorectal
excision. Ninety-three patients had palliative resections. There were four
locoregional recurrences in this group, giving an actuarial locoregional
recurrence rate of 9.3 percent at five years. The actuarial locoregional
recurrence rate after anterior resection was 6.5 percent at five years. The
actuarial five-year cancer-specific survival rate was 81.4 percent at five years.
CONCLUSION: These results demonstrate that a policy of wide excision of the
mesorectum for upper rectal and rectosigmoid cancer and total mesorectal excision
for mid and low rectal cancer is associated with a low locoregional recurrence
rate and may be as efficacious as routine total mesorectal excision for all
rectal cancers.
PMID- 11005490
TI - Does technique of anastomosis play any role in developing late perianal abscess
or fistula?
AB - PURPOSE: This study examines the risk factors for developing perianal abscess or
fistula formation after ileal pouch-anal anastomosis procedure for chronic
ulcerative colitis or familial adenomatous polyposis. METHODS: A total of 1,457
patients with J-pouch, 1,304 (89.5 percent) with chronic ulcerative colitis and
153 (10.5 percent) with familial adenomatous polyposis who had a two-stage
procedure without any evidence of previous perianal disease were included in the
study. The effect of pouch-to-anal anastomosis type on perianal abscess or
fistula formation was evaluated. RESULTS: A total of 108 patients (7.4 percent)
had a perianal abscess or fistula after the ileal pouch-anal anastomosis
procedure after at least one year of follow-up. No statistically significant
difference was identified in fistula formation regarding the age and gender of
the patients (P > 0.05), nor did the risk of fistula formation differ
significantly between the patients with handsewn vs. stapled anastomoses (P >
0.05). However, patients with a diagnosis of chronic ulcerative colitis, compared
with patients with familial adenomatous polyposis, had a statistically higher
risk of developing abscess or fistula (P = 0.012). CONCLUSION: The most important
risk factor in developing perianal sepsis in long-term patients with ileal pouch
anal anastomosis is the initial disease type. After excluding patients without
Crohn's disease, the risk of developing an abscess or fistula was found to be
significantly greater in patients with chronic ulcerative colitis compared with
patients with familial adenomatous polyposis, and this risk is independent of
anastomotic technique.
PMID- 11005491
TI - Laparoscopic-assisted colonoscopic polypectomy: the Texas Endosurgery Institute
experience.
AB - PURPOSE: The advent of laparoscopic surgery has altered the manner by which
surgical specialties address pathologies of the abdominal cavity. This advance in
technology has also changed colorectal surgery. One of the more common procedures
of colorectal surgery is segmental resection for polyps that are large, broad
based, or inaccessible for colonoscopic removal. We present a technique combining
colonoscopy and laparoscopy to remove troublesome polyps without the need for
segmental resections. METHODS: From May 1990 to September 1999 laparoscopic
monitored colonic polypectomies were performed in 47 patients, with a total of 60
polyps being removed. After laparoscopic mobilization of the involved segment of
the colon, the proximal bowel is cross-clamped and the colonoscope passed to the
involved portion of the colon. The polyp is then presented to the colonoscopist
by the laparoscopist facilitating removal. The serosal surface is monitored for
any indications of transluminal injury, and the area is repaired if needed. All
polyps undergo immediate frozen section analysis. If the pathologic evaluation
indicates malignancy then a segmental resection may be performed, otherwise the
patients are decompressed and fed within a short time before discharge. RESULTS:
The polyps were located most commonly in the ascending colon (18 polyps),
transverse colon (12 polyps), and cecum (12 polyps). The most common
histopathologic diagnosis was tubulovillous adenoma in 28 polyps followed by
villous adenoma in 11 polyps. In three cases histopathologic diagnosis revealed
malignancy necessitating segmental resection (1 low anterior resection and 2
right hemicolectomies), which were performed laparoscopically. Patients received
a liquid diet within 6 hours, were discharged in an average of 21 hours, and
returned to full activity, usually within days. The only complication presented
in this group of patients was an umbilical port seroma. Virtually all patients
(97 percent) behaved as if only a colonoscopy had been performed. Pain at the
trocar sites was managed with acetaminophen 600 mg by mouth as needed.
CONCLUSION: Laparoscopic-monitored colonoscopic polypectomy allows patients to
undergo removal of colonic polyps without a segmental resection. This less
invasive procedure yields recovery times similar to that of colonoscopy alone,
and the potential complications of a segmental resection are avoided. All polyps
are examined by frozen section, and if a malignancy is encountered, a
laparoscopic resection can be performed.
PMID- 11005492
TI - Loss of standard type of CD44 expression in invaded area as a good indicator of
lymph-node metastasis in colorectal carcinoma.
AB - PURPOSE: Recent advances have made possible the treatment of small invasive
colorectal cancer by means of polypectomy or endoscopic mucosal resection. CD44
expression in cancer cells was identified as an indicator of lymph-node
metastasis, which could be evaluated in specimens removed by colonoscopy.
METHODS: The correlation between lymph-node metastasis and the expression of
standard-type CD44 in cancer cells was examined immunohistologically using the
invaded cancer cells of 61 tissue samples of superficially invasive colorectal
cancer. We defined the above as invasive cancer restricted within the colorectal
wall. Of the 61 samples, 31 had submucosal invasion and 30 had muscular invasion.
RESULTS: Standard-type CD44 expression in the area of invasion in cases with
lymph-node metastasis was remarkably down-regulated. In 43 cases with no lymph
node metastasis, 36 (83.7 percent) of patients had CD44 expression in invaded
cells, whereas only two of 18 cases (11.1 percent) with lymph-node metastasis had
expression of standard-type CD44 in the same area (P < 0.0001). A total of 69.6
percent (16/23) of patients with loss of standard-type CD44 expression in invaded
sites were found to have positive metastasis in the lymph nodes. These results
suggest that standard-type CD44 in invasive colon cancer cells could suppress
metastasis to the regional lymph nodes. CONCLUSION: In cases of invasive
colorectal cancer, the loss of standard-type CD44 expression in the invaded area
is a sensitive marker for metastasis to the lymph nodes. Further investigation
with larger patient groups is required to clarify the reliability of loss of
standard-type CD44 expression as an indicator for additional surgery after
endoscopic resection of submucosal invasive colorectal carcinoma.
PMID- 11005493
TI - Results of neurophysiologic evaluation in fecal incontinence.
AB - PURPOSE: Several methods of neurophysiologic assessment exist in the
investigation of patients with fecal incontinence. However, the clinical
significance of the information gained is uncertain. The aim of this prospective
study was to evaluate the results of pudendal nerve terminal motor latency and
fiber density in relation to clinical variables and manometric measurements.
METHODS: Seventy-two patients with fecal incontinence (63 women; mean age, 62;
range, 24-81 years) responded to a bowel questionnaire and underwent anorectal
manovolumetry, anal ultrasonography, defecography, and electromyography,
including pudendal nerve terminal motor latency and fiber density. RESULTS:
Pudendal neuropathy (pudendal nerve terminal motor latency > 2.5 ms) was found in
46 percent and increased fiber density (> 1.7) in 82 percent. Pudendal neuropathy
and increased fiber density were most common in patients with rectal prolapse or
intra-anal intussusception. No difference was seen concerning anal resting and
incremental pressures, rectal compliance, rectal sensibility or severity of
incontinence in patients with unilateral, bilateral, or marked (> 4 ms) pudendal
neuropathy vs. patients with normal pudendal nerve terminal motor latency. In
contrast, patients with increased fiber density had lower incremental pressures
(P < 0.05) and stated decreased rectal sensibility (P < 0.05) compared with those
with normal fiber density. These differences were most pronounced in patients
with neurogenic or idiopathic incontinence. CONCLUSIONS: Pudendal neuropathy and
increased fiber density are common in patients with fecal incontinence. Fiber
density but not pudendal nerve terminal motor latency was correlated with
clinical and manometric variables. The severity of nerve injury correlated with
anal motor and sensory function in patients with neurogenic or idiopathic
incontinence. The routine use of pudendal nerve terminal motor latency in the
assessment of patients with fecal incontinence can be questioned.
PMID- 11005494
TI - Long-term results of electromyographic biofeedback training for fecal
incontinence.
AB - PURPOSE: The aim of this study was to examine the long-term results of
electromyographic biofeedback training in fecal incontinence. METHODS: Thirty
seven patients (1 male) received a customised program of 2 to 11 (median, 3)
biofeedback training sessions with an anal plug electromyometer. Nine patients
had persistent incontinence after anal sphincter repair, a further 8 patients had
postsurgical or partial obstetric damage of the sphincter but no sphincter
repair, 9 patients had neurogenic sphincter damage, and 11 patients were
classified as having idiopathic fecal incontinence. Duration of voluntary
sphincter contraction was measured by anal electromyography (endurance score)
before and after treatment. A postal questionnaire was used to investigate the
following variables: 1) subjective rating on a four-grade Likert-scale of the
overall result of the biofeedback training; 2) incontinence score (maximum score
is 18, and 0 indicates no incontinence); and 3) rating of bowel dissatisfaction
using a visual analog scale (0 to 10). RESULTS: Twenty-two patients (60 percent)
rated the result as very good (n = 8) or good (n = 14) immediately after the
treatment period. Median endurance score improved from 1 to 2 minutes (P <
0.0001). Median incontinence score improved from 11 to 7, and bowel
dissatisfaction rating improved from 5 to 2.8 (both P < 0.0001). After a median
follow-up of 44 (range, 12-59) months, 15 patients (41 percent) still rated the
overall result as very good (n = 3) or good (n = 12). The incontinence score did
not change during follow-up. Median bowel dissatisfaction rating deteriorated
from 2.8 to 4.2 but remained better than before treatment. Poor early subjective
rating and the need for more than three biofeedback sessions were predictive of
worsening during follow-up. CONCLUSION: We think it is encouraging that in this
study biofeedback treatment for fecal incontinence with an intra-anal plug
electrode resulted in a long-term success rate in nearly one-half of the
patients.
PMID- 11005495
TI - Treatment of impaired defecation associated with rectocele by behavorial
retraining (biofeedback).
AB - PURPOSE: Large rectoceles have been associated with symptoms of impaired rectal
evacuation, often leading to rectocele repair. However, these symptoms, or the
anatomic abnormality, may be caused, at least in part, by a primary disturbance
of rectoanal coordination. This study aimed to determine the efficacy of
biofeedback therapy in such patients. METHODS: Thirty-two female patients (median
age, 52 years) complaining of impaired rectal evacuation and with a rectocele
greater than 2 cm at proctography were evaluated by structured questionnaire
before, immediately after treatment, and at follow-up. Physiologic and
proctographic findings were related to outcome. RESULTS: Immediate results were
available in 32 patients and medium-term follow-up (median, 10; range, 2-30
months) in 25 patients. At follow-up 14 (56 percent) patients felt a little and 4
(16 percent) patients felt major improvement in symptoms, including 3 (12
percent) with complete symptom relief. Immediately after biofeedback there was a
modest reduction in need to strain (from 72 to 50 percent), feeling of incomplete
evacuation (from 78 to 59 percent), need to assist defecation digitally (from 84
to 63 percent), and need to use an evacuant (from 47 to 28 percent), and this was
maintained at follow-up. Bowel frequency was significantly normalized at follow
up (P = 0.02). Pretreatment presence of symptoms of digitally assisting
defecation, pelvic floor incoordination, and proctographic rectocele size and
contrast trapping, did not predict outcome. CONCLUSIONS: Behavioral therapy,
including biofeedback, leads to major symptom relief in a minority, and partial
symptom relief in a majority, of patients with a feeling of impaired defecation
and the presence of a large rectocele. Residual symptoms are common. Biofeedback
may be a reasonable first-line treatment for such patients.
PMID- 11005496
TI - Recurrent rectal prolapse: what is the next good option?
AB - PURPOSE: The aim of this study was to assess the clinical and functional outcome
of surgery for recurrent rectal prolapse and compare it with the outcome of
patients who underwent primary operation for rectal prolapse. METHODS: All
patients who underwent surgery for rectal prolapse were evaluated for age,
gender, procedure, anorectal manometry and electromyography findings, and
morbidity. The results for patients who underwent surgery for recurrent rectal
prolapse were compared with a group of patients matched for age, gender, surgeon,
and procedure who underwent primary operations for rectal prolapse. RESULTS: A
total of 115 patients underwent surgery for rectal prolapse. Twenty-seven
patients, 10 initially operated on at this institution and 17 operated on
elsewhere, underwent surgery for recurrent rectal prolapse. These 27 patients
were compared with 27 patients with primary rectal prolapse operated on in our
department. In the recurrent rectal prolapse group, prior surgery included
rectopexy in 7 patients, Delorme's procedure in 7 patients, perineal
rectosigmoidectomy in 7 patients, anal encirclement procedure in 4 patients, and
resection rectopexy in 2 patients. Operations performed for recurrence were
perineal rectosigmoidectomy in 14 patients, resection rectopexy in 8 patients,
rectopexy in 2 patients, pelvic floor repair in 2 patients, and Delorme's
procedure in 1 patient. There were no statistically significant differences
between the groups in preoperative incontinence score (recurrent rectal prolapse,
13.6 +/- 7.8 vs. rectal prolapse, 12.7 +/- 7.2; range, 0-20) or manometric or
electromyography findings, and there were no significant differences in mortality
(0 vs. 3.7 percent), mean hospital stay (5.4 +/- 2.5 vs. 6.9 +/- 2.8 days),
anastomotic complications (anastomotic stricture (0 vs. 7.4 percent), anastomotic
leak (3.7 vs. 3.7 percent) and wound infection (3.7 vs. 0 percent), postoperative
incontinence score (2.8 +/- 4.8 vs. 1.5 +/- 2.7), or recurrence rate (14.8 vs.
11.1 percent) between the two groups at a mean follow-up of 23.9 (range, 6-68)
and 22 (range, 5-55) months, respectively. The overall success rate for recurrent
rectal prolapse was 85.2 percent. CONCLUSION: The outcome of surgery for rectal
prolapse is similar in cases of primary or recurrent prolapse. The same surgical
options are valid in both scenarios.
PMID- 11005497
TI - Primary colorectal lymphoma.
AB - PURPOSE: The purpose of this study was to review the clinical presentation and
characteristics of primary colorectal lymphoma, analyze the prognostic factors,
and assess the results of treatment with adjuvant chemotherapy. METHODS: We
identified 37 cases at our institution between 1980 and 1996. They comprised 0.48
percent of all cases of colon malignancies (37/7,658) during this period. The
following clinical information was obtained: age, gender, signs and symptoms,
tumor site, tumor size, histology grade, pathology, and adjuvant chemotherapy.
RESULTS: The most common presenting signs and symptoms were abdominal pain (62
percent), abdominal mass (54 percent), and weight loss (43 percent). The most
frequent site of involvement was the cecum (45 percent). Histologically, 29 (78
percent) were classified as high-grade, and 8 (22 percent) as intermediate-grade
to-low-grade lymphoma. Nine (24.3 percent) of the cases were Stage EI, 23 (62.2
percent) were Stage EII, and 5 (13.5 percent) were Stage EIV. Twenty-one (57
percent) cases received adjuvant chemotherapy. The five-year survival rate was 33
percent for all patients and 39 percent for patients treated with combination
chemotherapy. Overall median survival time was 24 months and 36 months for those
with adjuvant chemotherapy. Only histology grade, among the factors examined, was
a significant prognostic factor for survival. The mean survival time of the
patients with Stage II disease who received chemotherapy was 117.4 months, and it
was 47.9 months for the patients with Stage II disease who did not received
chemotherapy. CONCLUSIONS: In our retrospective study high-grade lymphoma was the
only significant adverse prognostic factor for survival. Receiving adjuvant
chemotherapy significantly improved survival in patients with Stage II disease.
Patients with diffuse large-cell type had better survival than patients with
small noncleaved-cell type in Stage II high-grade lymphoma.
PMID- 11005498
TI - Effects of rectal mobilization and lateral ligaments division on colonic and
anorectal function.
AB - PURPOSE: Colonic and anorectal function are altered after posterior rectopexy.
The aim of this randomized, prospective study was to evaluate the effects of
rectal mobilization and division of the lateral ligaments on colonic and
anorectal function. METHODS: Posterior rectopexy was performed in 18 patients
with complete rectal prolapse. Anal manometry and measurement of rectal
compliance, total and segmental colonic transit time, constipation score, and
defecation frequency were performed preoperatively and three months
postoperatively. Ligaments were divided in ten patients. RESULTS: Mean
preoperative total transit time was similar between the two patient groups and
doubled postoperatively (P = 0.03). Mean postoperative segmental transit time
increased by a factor of 1.7 in segments I (ascending colon) and II (descending
colon) and by a factor of 2.3 in segment III (rectosigmoid). The same pattern was
found in both groups. Mean resting pressure decreased after division of the
lateral ligaments and increased after preservation. Mean rectal compliance
decreased after division of the ligaments and increased when they were preserved.
Mean postoperative constipation score differed little from the preoperative
score. Mean defecation frequency was decreased in the group with the ligaments
preserved and increased in the group with the ligaments divided. None of the
effects of rectal mobilization or division of the lateral ligaments on anorectal
function reached statistical significance. CONCLUSION: Rectal mobilization had a
statistically significant effect on colonic function. Total and segmental colonic
transit times doubled. The effects on anorectal function were not significant.
Division of the lateral ligaments did not significantly influence postoperative
functional outcome.
PMID- 11005499
TI - Transanally injected triamcinolone acetonide in levator syndrome.
AB - PURPOSE: Several treatments are used for the treatment of levator syndrome, such
as rectal massage, biofeedback, and galvanic stimulation. But their effects are
inconsistent, and multiple treatment sessions are usually required. Triamcinolone
acetonide and lidocaine mixture was injected locally into the tenderest point in
levator syndrome under the hypothesis that levator syndrome is caused by
tendinitis of pelvic floor musculature. METHODS: A mixture of 40 mg of
triamcinolone acetonide and 1 ml of 2 percent lidocaine was injected into the
tenderest point transanally in 104 patients (33 males; mean age, 51 years) with
levator syndrome from December 1996 to May 1998 at Daehang Clinic. Additional
injections were repeated at two-week intervals to a maximum of three injections
in cases of poor response. Follow-up was performed prospectively concerning
patient's perception of pain level using a visual analog scale. Depending on the
response, the patients were classified into four groups: pain-free, good, fair,
and no response. More than 50 percent pain reduction was classified as "good,"
and less than 49 percent reduction as "fair." RESULTS: The injection regions,
where the tenderest points were identified on digital rectal compression, were
left anterior anal canal in 71.2 percent of patients, right anterior in 3.8
percent of patients, and posterior in 25 percent of patients. The results of
treatment were as follows: at three months after injection, response was
classified as pain-free in 36.8 percent of patients, good in 35 percent of
patients, fair in 19.5 percent of patients, and no response in 8.7 percent of
patients; at six months the response was pain-free in 30.1 percent of patients,
good in 46.5 percent of patients, fair in 18.2 percent of patients, and no
response in 5.2 percent of patients. Most patients, except 8.7 percent at three
months and 5.2 percent at six months, experienced treatment benefits. There were
no complications during the follow-up periods. CONCLUSION: Transanal injection of
triamcinolone acetonide and lidocaine mixture into the tenderest point is such a
simple, safe, and very effective modality that it can be recommended as a primary
therapy for levator syndrome.
PMID- 11005500
TI - Bile carcinoembryonic antigen levels and occult hepatic metastases from
colorectal cancer.
AB - PURPOSE: Up to 30 percent of patients will have occult hepatic metastases at the
time of curative surgery for colorectal cancer. The ability to predict this group
of patients would allow better targeting of appropriate therapy. It has been
shown previously that patients with overt hepatic metastases have significantly
high levels of carcinoembryonic antigen in gallbladder bile compared with serum
levels. The aim of this study was to assess the accuracy of bile carcinoembryonic
antigen levels taken at the time of operation in predicting patients with occult
hepatic metastases. METHODS: Bile and serum carcinoembryonic antigen samples were
collected from 37 patients undergoing surgery for colorectal cancer, 26 of whose
procedures were deemed curative and who were followed up for a median of 63.5
months. RESULTS: Twelve patients were alive with no evidence of recurrent
disease, and two had recurrent disease, whereas 12 died of disease. The median
(interquartile range) serum carcinoembryonic antigen in the disease-free group
was 2.8 (1.1-6.1) ng/ml, and in the recurrent group it was 6.35 (4.3-30) ng/ml (P
= 0.006), whereas bile carcinoembryonic antigen in the disease-free group was 7
(5-39) ng/ml as compared with 31 (5-383.7) ng/ml in the recurrent group (P =
0.210). The accuracy of serum carcinoembryonic antigen in predicting occult
hepatic metastases was 77 percent compared with 72 percent for bile
carcinoembryonic antigen. CONCLUSION: Intraoperative bile carcinoembryonic
antigen levels are no more accurate than serum carcinoembryonic antigen levels in
predicting occult hepatic metastases in patients undergoing potentially curative
colorectal cancer surgery.
PMID- 11005501
TI - Impact of previous surgery on time taken for incision and division of adhesions
during laparotomy.
AB - PURPOSE: Adhesions from previous surgery constitute a major problem in general
surgery. Much is known of the consequences of adhesions in terms of morbidity,
but there has been little documentation of the effect of previous surgery on the
time taken to reoperate. METHODS: Information on incision time and division of
adhesion time was recorded on 120 patients (89 elective cases and 31 emergencies)
undergoing midline laparotomy under the care of a single colorectal surgeon.
RESULTS: Fifty-one percent of elective and 71 percent of emergency cases had
previously had abdominal surgery. Previous surgery prolonged the median incision
time from 5 (range, 3-10) to 8 (range, 4-39) minutes (P < 0.001) and the median
division of adhesion time from 0 (range, 0-30) to 15 (range, 0-12) minutes (P <
0.0001). CONCLUSIONS: Previous surgery significantly increases the operating time
during subsequent surgery by a median of 18 minutes. This information may be of
use in the planning of surgical workload and highlights the needs for cost
effective adhesion prevention strategies.
PMID- 11005502
TI - Fournier's gangrene: changing face of the disease.
AB - PURPOSE: Our experience with ten cases of Fournier's gangrene prompted us to
review the related literature to highlight the current status of the disease.
METHODS: Data from ten patients with the diagnosis of Fournier's gangrene treated
at our center from January 1997 until December 1998 were analyzed. These patients
were treated by aggressive resuscitation, triple antibiotics, and urgent surgery.
The English-language medical literature for the past 30 years was reviewed.
RESULTS: The epidemiologic features of our patients were similar to those
reported in other recent studies. Mortality rate was 20 percent. Currently, the
disease affects both genders and a wide range of ages, has a more insidious onset
than in the past, and is not idiopathic. Associated systemic disorders (diabetes,
alcoholism, and immunosuppression) are common. Perianal infection is the
commonest cause and is associated with more moribund features. CONCLUSION: The
epidemiology of Fournier's gangrene is changing from its original description.
Population aging worldwide--as a result of improving health care--and therefore
the increasing prevalence of associated medical disorders may explain these
changes. These factors may also explain the consistently high mortality rate
during more recent years, masking any survival benefits from improved medical
care. Better understanding of the pathophysiology has reduced the ratio of
idiopathic cases to a minimum.
PMID- 11005503
TI - Hyperplastic polyps: "more than meets the eye"? Report of sixteen cases.
AB - The vast majority of hyperplastic polyps are small, left-sided, and
inconsequential in nature. However, hyperplastic polyps that are large, right
sided, mixed, and found in association with a family history of carcinoma may
represent an "atypical" group, and their clinical significance is uncertain. We
believe that these atypical lesions should not be lumped together with the common
variety of diminutive hyperplastic polyps. Rather, when such hyperplastic polyps
are encountered, they should be excised and the patient should be placed on
regular colonoscopic surveillance.
PMID- 11005504
TI - Synchronous colorectal and renal carcinomas: a noteworthy clinical entity. Report
of five cases.
AB - PURPOSE: This study was designed to highlight the incidence of synchronous
colorectal and renal carcinomas and to review the literature on that issue. The
case reports of five patients who presented with synchronous colorectal and renal
cell carcinomas are presented. METHODS: A retrospective study, using systematic
medical chart review, analyzed the cases of all patients who underwent large
bowel resection for colorectal cancer in our department between December 1996 and
December 1998. RESULTS: Among 103 patients who underwent colorectal surgery
during that period, five cases of synchronous colorectal and renal carcinomas
were detected (4.85 percent). CONCLUSIONS: Based on our findings, we recommend
the routine use of preoperative imaging studies to exclude synchronous
asymptomatic renal lesions in patients presenting with colorectal cancer.
PMID- 11005505
TI - Gastrointestinal stromal tumor of the rectum with activating mutation of c-kit:
report of a case.
AB - Nonepithelial malignancies of the large bowel are rare. A new disease entity,
gastrointestinal stromal tumors, has attracted attention among primary
mesenchymal tumors of the gastrointestinal tract. Here we present a case of
spindle-cell sarcoma of the rectum, lacking either smooth muscle cells or neural
elements. Immunohistochemical findings and sequencing of the c-kit proto-oncogene
diagnosed this tumor as a malignant gastrointestinal stromal tumor of the rectum.
PMID- 11005506
TI - Thermal imaging in the detection of bowel ischemia.
AB - PURPOSE: The aim of this study was to introduce thermal imaging in the
intraoperative detection of bowel ischemia by comparing thermal imaging with
conventional techniques in detecting acutely ischemic bowel, using histologic
evidence for intestinal necrosis as the standard. METHODS: A prospective study
was performed using a porcine model. Laparotomy was performed on four pigs under
general anesthesia. A 25-cm segment of mid jejunum was tagged with proximal and
distal sutures, and its mesentery was ligated and divided. Thermal imaging,
visual inspection, Doppler ultrasound, and fluorescence with Wood's lamp after
fluorescein were used to estimate the extent of bowel ischemia five minutes after
ligation of the mesentery. Measurements were taken in reference to both the
proximal and distal tags to obtain two data points per animal for each method.
After two hours of warm ischemia, the jejunum was harvested and sectioned
longitudinally. Comparisons were made between the estimated region of necrosis
for each method and microscopic evidence of necrosis. RESULTS: Visual inspection
was the only method unable to detect a difference between vascularized and
devascularized bowel for each of the eight data points. Fluorescein dye missed 3
cm of ischemic bowel. Doppler ultrasound and thermal imaging were 100 percent
sensitive for necrotic bowel, with thermal imaging overestimating necrosis to a
greater extent than Doppler ultrasound. The positive predictive value of
fluorescein dye, Doppler ultrasound, and thermal imaging for determining
nonviable bowel was 91.8, 80.8, and 69.5 percent, respectively. CONCLUSIONS:
Thermal imaging has the potential to be a useful adjunct in the intraoperative
determination of bowel ischemia. Further studies are indicated to study this
technique.
PMID- 11005507
TI - Laparostomy for severe intra-abdominal infection complicating colorectal disease.
PMID- 11005508
TI - Escape mechanisms in tumor immunity: a year 2000 update.
AB - The current consensus of opinion has it that most or possibly all tumors,
spontaneous as well as induced, are immunogenic, expressing antigens in a form
recognizable by the host immune system. Accordingly, in order to progress, tumors
have to evolve strategies for evading immune responses. The purpose of this
review is to consider the current status of knowledge concerning these different
tumor escape strategies. It represents an update of an article originally
published in this journal in 1997 (Pawelec, Zeuthen, and Kiessling, 1997).
Therefore, it focuses mostly on publications that have appeared since then,
illustrating the impressive accumulation of new data since that time and the
importance currently attributed to studies of tumor escape from the immune
response.
PMID- 11005509
TI - Vascular endothelial growth factor and osteopontin in tumor biology.
AB - Tumor growth and metastasis are angiogenesis-dependent and tumor angiogenesis is
a result of complex interplay of positive and negative regulators. Vascular
endothelial growth factor (VEGF) occupies a particular place among the positive
regulators of angiogenesis due to its potency and specificity for endothelial
cells. VEGF upregulates several molecules such as growth factors, adhesion
molecules, proteases, and protease receptors and it actually induces
microvascular hyperpermeability, resulting in activation of thrombin from
prothrombin. Osteopontin (OPN) is a secreted arginine-glycine-asparic acid (RGD)
containing phosphoprotein and it contains a predicted thrombin cleavage site. OPN
binds to several integrins and CD44 variants. OPN has diverse functions such as
cell adhesion, chemoattraction, and immunomodulation, and it induces endothelial
cell migration and upregulates endothelial cell migration induced by VEGF. OPN
expression is upregulated in human carcinomas. This review documents the
functional roles of VEGF and OPN in angiogenesis and their clinical significance
in tumor biology.
PMID- 11005510
TI - Differentiation and metastasis in melanoma.
AB - The incidence of melanoma has been rising steadily during the last four decades
and is now among the highest of all human cancers. As for most tumors, malignancy
and metastatic spreading represent the deadly aspects of a tumor that, if
eradicated before becoming invasive, can be easily cured. In fact, melanoma
metastatic to regional lymph nodes carries a poor prognosis, and distant
metastatic melanoma becomes incurable. Because traditional forms of chemotherapy
have little effect on this type of tumor, differentiation therapy has been
considered as a possible alternative, based on the consideration that malignancy
and differentiation are usually inversely related. However, the relationship
between these two factors turned out to be more complex for melanoma cells, and
in some murine model systems it has been found that differentiated cells,
although less tumorigenic, could be even more metastatic. No clear correlation
has been reported between (epi)genetic changes induced by differentiating drugs
and the increased malignant phenotype. This review examines what is known to date
about differentiation state and metastatic ability of melanomas, and also reports
some novel data with the B16 mouse melanoma model system.
PMID- 11005511
TI - Impact of viral oncogenesis on responses to anti-cancer drugs and irradiation.
AB - The view that chemical or physical oncogenesis and tumor therapy resistance
represent different parts of common cellular alterations gained considerable
attractiveness, because it explains the inherent unreponsiveness of many tumors.
Viruses are potent oncogenes and are causally linked to approximately one-fifth
of all human malignancies. Whether viral oncogenesis exerts comparable effects
was less clear. Recent progress in experimental research provided ample evidence
that viruses affect response of tumor cells toward anti-cancer drugs and
irradiation. Resistance to cytostatic drugs and radiation develops by alterations
at the drug-target sites (i.e., DNA or specific target proteins), upstream (i.e.,
detoxification mechanisms), or downstream of them (i.e., programmed cell death).
Viruses interfere with specific cellular genes at these three levels. Viral
proteins induce the expression and expression of drug resistance genes, that is,
MDR1, DHFR, or CAD. Viral interactions with the tumor suppressor genes (p53, pRB)
abrogate cell cycle arrests and disturb DNA repair of drug- and radiation-induced
DNA lesions. The readiness to commit cellular suicide (apoptosis) is also
affected by viral genes. The connection between viral oncogenesis and the
response of tumor cells to treatment adds a new dimension to tumor biology and
may have important consequences for oncological treatment modalities in the
future.
PMID- 11005512
TI - Extended slide trochanteric osteotomy for revision total hip arthroplasty.
AB - BACKGROUND: The purpose of this study was to assess the rate of union, time to
union, and complications associated with the extended slide trochanteric
osteotomy. We also evaluated how outcomes were influenced by the preoperative
cortical-bone thickness, the preoperative cancellous-bone quality of the greater
trochanter, the number of cables used to reattach the trochanteric osteotomy
fragment, and the use of cortical strut augmentation. METHODS: We reviewed the
results for forty-six hips in forty-five patients who underwent a revision total
hip arthroplasty with an extended slide trochanteric osteotomy between December
1991 and December 1996. Twenty-three patients were men, and twenty-two were
women; the mean age at the time of the operation was 66.3 years. Two hips had an
isolated acetabular revision, fifteen had an isolated femoral revision, and
twenty-nine had acetabular and femoral revisions. One patient (one hip) was lost
to follow-up. RESULTS: At a mean of forty-four months after the operation, the
rate of union of the distal osteotomy site was 98 percent (forty-four of forty
five hips), with no change in the femoral component position. The time to union
was not significantly correlated with the number of cables, the preoperative
cortical-bone thickness, or the preoperative cancellous-bone quality of the
greater trochanter. Interestingly, the time to bridging-callus union was
significantly longer in the hips with a strut allograft than in the hips without
a strut allograft (p = 0.04, t test for independent samples). Two fractures of
the osteotomy fragment occurred, but neither necessitated another revision.
CONCLUSIONS: The extended slide trochanteric osteotomy allows extensive
acetabular and femoral exposure, facilitates removal of distal cement or a well
fixed porous-coated stem, and allows reliable reattachment and healing of the
trochanteric fragment.
PMID- 11005513
TI - Capsulolabral augmentation for the the management of posteroinferior instability
of the shoulder.
AB - BACKGROUND: Posteroinferior instability of the shoulder has been associated with
capsular laxity. The purposes of the present study were to describe the
pathological morphology of the posteroinferior aspect of the glenolabral fossa in
patients with primary posteroinferior instability and to prospectively examine
the efficacy of managing this instability with use of an arthroscopic
posteroinferior capsulolabral augmentation procedure. METHODS: Forty-one patients
who had posteroinferior instability of the shoulder were managed with an
arthroscopic shift of the posteroinferior aspect of the capsule to the adjacent
labrum and were followed for a minimum of twelve months. Thirty-two patients had
a primary procedure, and nine had a revision procedure. The mean duration of
follow-up was twenty-eight months (range, twelve to sixty-nine months). All of
the patients had presented with a symptomatic, positive finding on the jerk test
and had participated in a minimum of six months of rehabilitation that had failed
to relieve the symptoms. The patients were evaluated prospectively with a motion
and stability examination and the Simple Shoulder Test. In addition, they
completed the Short Form-36 Health Survey (SF-36) and a questionnaire on the
outcome of treatment. RESULTS: Lesions affecting the posteroinferior aspect of
the glenolabral concavity were seen in thirty-four patients (83 percent): five
had labral detachment, seven had chondral or labral erosion, nine had capsular
and synovial stripping, and thirteen had a labral split or tear. The mean score
(and standard deviation) on the Simple Shoulder Test improved from 5.5 +/- 3.4
points to 8.1 +/- 3.3 points (p = 0.0023), and two of the eight SF-36 parameters
improved significantly (p < 0.05). Conversely, nineteen patients who were
receiving Workers' Compensation did not show any improvement in either of the two
parameters. Thirty-five patients had improved stability of the shoulder, and the
findings on all physical examinations had improved significantly (p < 0.0001).
Twenty-eight patients had a perception of residual stiffness; this finding was in
contrast to the mean score on the flexibility examination, which had not changed
significantly at the time of the latest follow-up. CONCLUSIONS: Posteroinferior
instability of the shoulder is associated not only with capsular laxity but also
with well defined lesions of the glenolabral concavity. Arthroscopic
capsulolabral augmentation to reduce posterior capsular laxity and to restore the
depth of the glenolabral concavity has been shown to be effective treatment of
this condition after a mean duration of follow-up of twenty-eight months.
PMID- 11005514
TI - Arthroplasty of the hip in patients with aplastic anemia.
AB - BACKGROUND: Patients with aplastic anemia are now living longer and therefore are
at increased risk for the development of osteonecrosis of the hip. However,
studies on the results of arthroplasty for the treatment of osteoarthritis of the
hip in patients with aplastic anemia are lacking. METHODS: Twenty-six primary hip
prostheses (one bipolar prosthesis fixed with cement, two bipolar prostheses
fixed without cement, three hybrid total hip prostheses, and twenty total hip
prostheses fixed without cement) were implanted, between March 1990 and May 1992,
in nineteen patients who had been diagnosed with aplastic anemia. A specific
prospective protocol was followed for the perioperative transfusion of platelets
and blood. Twenty-five hips were replaced because of osteonecrosis of the femoral
head, and one was replaced because of a femoral neck fracture. The patients were
followed prospectively, with preoperative and serial postoperative Harris hip
ratings as well as radiographs, for a minimum of six years or until death.
RESULTS: No patient had excessive perioperative bleeding or a postoperative
infection. After a mean duration of follow-up of seventy-nine months (range,
seventy-two to ninety-five months), two patients had died with the original
implant in place. No patients were lost to follow-up. The mean Harris hip score
was 55 points (range, 42 to 68 points) preoperatively and 87 points (range, 56 to
95 points) at the time of the latest follow-up. At the time of this writing, no
hip had been revised. One patient with a bipolar prosthesis had radiographic
evidence of femoral loosening and will probably require revision. A second
patient had some medial protrusion of a bipolar prosthesis, with mild symptoms.
All of the acetabular components that had been fixed without cement and all of
the other femoral components appeared to be stable on radiographs after a minimum
of seventy-two months of follow-up. CONCLUSIONS: Total hip arthroplasty can be
performed safely in patients with aplastic anemia. In the present intermediate
term study, the durability of implant fixation was maintained and the clinical
results demonstrated a sustained increase in function of the hip.
PMID- 11005515
TI - Noninvasive imaging predicts failure load of the spine with simulated osteolytic
defects.
AB - BACKGROUND: The clinical management of lytic tumors of the spine is currently
based on geometric measurements of the defect. However, the mechanical behavior
of a structure depends on both its material and its geometric properties.
Quantitative computed tomography and dual-energy x-ray absorptiometry were
investigated as noninvasive tools for measuring the material and geometric
properties of vertebrae with a simulated lytic defect. From these measures, yield
loads were predicted with use of composite beam theory. METHODS: Thirty-four
fresh-frozen cadaveric spines were segmented into functional spinal units of
three vertebral bodies with two intervertebral discs at the thoracic and lumbar
levels. Lytic defects of equal size were created in one of three locations: the
anterior, lateral, or posterior region of the vertebra. Each spinal unit was
scanned with use of computed tomography and dual-energy x-ray absorptiometry, and
axial and bending rigidities were calculated from the image data. Each specimen
was brought to failure under combined compression and forward flexion, and the
axial load and bending moment at yield were recorded. RESULTS: Although the
relative defect size was nearly constant, measured yield loads had a large
dispersion, suggesting that defect size alone was a poor predictor of failure.
However, image-derived measures of structural rigidity correlated moderately well
with measured yield loads. Furthermore, with use of composite beam theory with
quantitative computed tomography-derived rigidities, vertebral yield loads were
predicted on a one-to-one basis (concordance, r(c) = 0.74). CONCLUSIONS: Although
current clinical guidelines for predicting fracture risk are based on geometric
measurements of the defect, we have shown that the relative size of the defect
alone does not account for the variation in vertebral yield loads. However,
composite beam theory analysis with quantitative computed tomography-derived
measures of rigidity can be used to prospectively predict the yield loads of
vertebrae with lytic defects. CLINICAL RELEVANCE: Image-predicted vertebral yield
loads and analytical models that approximate loads applied to the spine during
activities of daily living can be used to calculate a factor of fracture risk
that can be employed by physicians to plan appropriate treatment or intervention.
PMID- 11005516
TI - Total knee arthroplasty after high tibial osteotomy. A comparison study in
patients who had bilateral total knee replacement.
AB - BACKGROUND: The outcome of total knee replacement after high tibial osteotomy
remains uncertain. We hypothesized that the results of total knee replacement
with or without a previous high tibial osteotomy are similar. METHODS: The
results of a consecutive series of thirty-nine bilateral total knee
arthroplasties performed with cement at an average of 8.7 years after unilateral
high tibial osteotomy were reviewed. There were twenty-seven men and twelve
women. Preoperatively, the knee scores according to the system of the Knee
Society were similar for all of the knees; however, valgus alignment and patella
infera were more common in the knees with a previous high tibial osteotomy.
Bilateral total knee replacement was staged in seven patients and was
simultaneous in thirty-two patients. The results of the total knee arthroplasties
were retrospectively reviewed with respect to the knee and function scores
according to the system of the Knee Society, the radiographic findings, and the
complications. RESULTS: Intraoperatively, no notable differences were identified
in the number of medial, lateral, or lateral patellar releases required. However,
less lateral tibial bone was resected in the group with a previous high tibial
osteotomy (average, 3.3 millimeters) than in the group without a high tibial
osteotomy (average, 7.5 millimeters). The average duration of follow-up was 7.5
years (range, three to sixteen years) in the group with a previous high tibial
osteotomy and 6.8 years (range, two to ten years) in the group without a high
tibial osteotomy. At the time of the final follow-up, the knee and function
scores were similar for the two groups (89.0 and 81.0 points, respectively, for
the group with a previous high tibial osteotomy, and 89.6 and 83.9 points,
respectively, for the group without a high tibial osteotomy). Although more knees
were free of pain in the group without a previous high tibial osteotomy (thirty
six) than in the group with a previous osteotomy (thirty-three), this difference
was not found to be significant with the numbers available (p = 0.4810). Knee
alignment and stability, femoral and tibial component alignment, and range of
motion also were similar in both groups postoperatively. One allpolyethylene
tibial component was revised in the high tibial osteotomy group. Two knees in
each group required manipulation. There were no deep infections. CONCLUSIONS:
While patients with a previous high tibial osteotomy may have important
differences preoperatively, including valgus alignment, patella infera, and
decreased bone stock in the proximal part of the tibia, the present study
suggests that the clinical and radiographic results of primary total knee
arthroplasty in knees with and without a previous high tibial osteotomy are not
substantially different. In our relatively small group of patients, the previous
high tibial osteotomy had no adverse effect on the outcome of the subsequent
total knee replacement.
PMID- 11005517
TI - Semiconstrained total elbow arthroplasty for ankylosed and stiff elbows.
AB - BACKGROUND: Total elbow arthroplasty can be a valuable option for the treatment
of ankylosed or very stiff elbows. METHODS: A semiconstrained total elbow
arthroplasty was performed in thirteen patients (fourteen elbows) with a
preoperative range of elbow motion of 30 degrees or less. Nine elbows were fused
or ankylosed preoperatively. The mean age at the time of the surgery was fifty
years (range, twenty-four to seventy-nine years). The etiology of the stiffness
was trauma for eleven elbows, juvenile rheumatoid arthritis for two, and
rheumatoid arthritis for one. RESULTS: After a mean duration of follow-up of
sixty-three months, the result was excellent for four elbows, good for four, fair
for one, and poor for five, according to the Mayo elbow performance score. The
mean arc of flexion improved from 7 degrees (range, 0 to 30 degrees)
preoperatively to 67 degrees (range, 10 to 115 degrees) after the surgery. The
most important factor that influenced the final result was the presence of
ectopic bone surrounding the elbow joint. There were seven complications.
Infection developed in five elbows. Three elbows had a superficial infection,
which did not compromise the final result in two and which was treated with a
myocutaneous flap in one with skin necrosis, with an excellent result. Deep
infection developed in two other elbows. Both had an unsatisfactory result, one
after implant removal and one after several debridements and retention of the
prosthesis. Two patients sustained a fracture because of a loose component, and
the prosthesis was revised. Four patients who lost motion within the first month
following the surgery had a manipulation under anesthesia. CONCLUSIONS:
Semiconstrained total elbow arthroplasty is a useful option for patients with an
ankylosed or a very stiff elbow and results in a considerable improvement of
motion. Because of the nature of the underlying pathology, complications,
including reoperation, are frequent, but the risk can be lessened by careful
preoperative planning and surgical technique. Replacement is the preferred option
in patients who are more than sixty years of age, but it is also a good choice in
younger patients if there is no other viable option.
PMID- 11005518
TI - Osteochondromas of the distal aspect of the tibia or fibula. Natural history and
treatment.
AB - BACKGROUND: There is little information on the natural history or treatment of
osteochondromas arising from the distal aspect of either the tibia or the fibula.
It is believed that there is a risk of deformation of the ankle if these
exostoses are left untreated or if the physis or neurovascular structures are
injured during operative intervention. METHODS: We reviewed the records of twenty
three patients who had been treated for osteochondroma of the distal aspect of
the tibia or fibula between 1980 and 1996. Four of the patients had hereditary
multiple cartilaginous exostoses. There were seventeen male and six female
patients, and the average age at the time of presentation was sixteen years
(range, eight to forty-eight years). RESULTS: Preoperative radiographs showed
evidence of plastic deformation of the fibula in eleven patients who had a large
osteochondroma. Four patients elected not to have an operation. The tumor was
excised in nineteen patients. Postoperatively, all nineteen patients had a
Musculoskeletal Tumor Society score of 100 percent for function of the lower
extremity with pain-free symmetrical and unrestricted motion of the ankle at the
latest follow-up examination. Partial remodeling of the tibia and fibula
gradually diminished the asymmetry of the ankles in all nineteen operatively
managed patients; however, the remodeling was most complete in the younger
patients. Pronation deformities of the ankle did not change after excision of the
tumor. Complications of operative treatment included four recurrences (only three
of which were symptomatic), one sural neuroma, one superficial wound infection,
and one instance of growth arrest of the distal aspects of the tibia and fibula.
CONCLUSIONS: Osteochondromas of the distal and lateral aspects of the tibia were
more often symptomatic than those of the distal aspect of the fibula; they most
commonly occurred in the second decade of life with ankle pain, a palpable mass,
and unrestricted ankle motion. Untreated or partially excised lesions in
skeletally immature patients may become larger and cause plastic deformation of
the tibia and fibula and a pronation deformity of the ankle. Ideally, operative
intervention should be delayed until skeletal maturity, but, in symptomatic
patients, partial excision preserving the physis may be necessary for the relief
of symptoms and the prevention of progressive ankle deformity. However, partial
excision is associated with a high rate of recurrence, so a close follow-up is
required. Skeletally mature patients who are symptomatic may require excision of
the tumor.
PMID- 11005519
TI - Atraumatic osteonecrosis of the knee.
AB - BACKGROUND: The purposes of this study were to define the clinical, demographic,
and radiographic patterns of atraumatic osteonecrosis of the distal part of the
femur and the proximal part of the tibia at presentation and to report the
outcome of treatment of this condition. METHODS: Two hundred and forty-eight
knees in 136 patients who were younger than the age of fifty-five years were
treated at our institution between July 1, 1974, and September 15, 1998, for
atraumatic osteonecrosis of the distal part of the femur or the proximal part of
the tibia, or both. Demographic and radiographic features were characterized. The
results of nonoperative treatment, core decompression, arthroscopic debridement,
and total knee arthroplasty were evaluated. RESULTS: There were 106 female
patients and thirty male patients, and their mean age was thirty-six years
(range, fifteen to fifty-four years) at the time of diagnosis. One hundred and
one patients (74 percent) had involvement of other large joints, with eighteen
(13 percent) presenting initially with knee symptoms. One hundred and one
patients (74 percent) had a disease that affected the immune system; sixty-seven
of them had systemic lupus erythematosus. One hundred and twenty-three patients
(90 percent) had a history of corticosteroid use. Technetium-99m bone-scanning
missed lesions in sixteen (29 percent) of fifty-six knees. Eight (20 percent) of
forty-one initially symptomatic knees treated nonoperatively had a successful
clinical outcome (a Knee Society score of at least 80 points and no additional
surgery) at a mean of eight years. The knees that remained severely symptomatic
for three months were treated with either core decompression (ninety-one knees)
or total knee arthroplasty (seven knees). Seventy-two (79 percent) of the ninety
one knees treated with core decompression had a good or excellent clinical
outcome at a mean of seven years. Efforts to avoid total knee arthroplasty with
repeat core decompression or arthroscopic debridement led to a successful outcome
in fifteen (60 percent) of twenty-five knees. Thirty-four (71 percent) of forty
eight knees treated with total knee arthroplasty had a successful clinical
outcome at a mean of nine years. CONCLUSIONS: Atraumatic osteonecrosis of the
knee predominantly affects women, and in our study it was associated with
corticosteroid use in 90 percent of the patients. Evaluation should include
standard radiographic and magnetic resonance imaging of all symptomatic joints.
Prognosis was negatively related to large juxta-articular lesions. Nonoperative
treatment should be reserved for asymptomatic knees only. Core decompression was
successful (a Knee Society score of at least 80 points and no additional surgery)
in 79 percent of the knees in which the disease was in an early stage. Total knee
arthroplasty was successful in only 71 percent of the knees.
PMID- 11005520
TI - Hybrid total hip arthroplasty with a precoated offset stem. Four to nine-year
results.
AB - BACKGROUND: Use of modern cementing techniques for fixation of femoral components
in total hip arthroplasty has had excellent clinical and radiographic results in
most patients. However, several authors have described early loosening of femoral
components with roughened and precoated finishes. The purpose of this study was
to examine the performance of the precoated Iowa stem, which has increased
offset, and to compare the results with those of another cemented precoated
femoral component with standard offset used at our institution. METHODS: We
carried out a prospective analysis of 102 primary hybrid total hip arthroplasties
(a cementless acetabular component and a cemented femoral component) performed
with use of the Iowa femoral component in ninety-five patients at our
institution. The Iowa stem was used in hips that required greater offset than is
available with standard stems as determined by preoperative templating. The
average age of the patients at the time of the index procedure was sixty-nine
years. Sixteen patients (seventeen hips) died before the forty-eight-month
minimum follow-up period had elapsed. Two patients were lost to follow-up, and
radiographic follow-up was incomplete for one. The mean duration of clinical and
radiographic follow-up of the remaining eighty-two hips in the seventy-six
surviving patients was sixty-five months (range, forty-eight to 104 months).
RESULTS: The average preoperative Harris hip score of 47 points (range, 16 to 69
points) improved to an average of 87 points (range, 24 to 100 points) at the time
of the review. Two hips underwent femoral component revision. Four femoral stems
were radiographically loose at an average of thirty-four months. Femoral
osteolysis was seen in five hips (6 percent) at an average of fifty-four months
postoperatively. No acetabular component was revised because of aseptic
loosening. According to Kaplan-Meier analysis, the seven-year survival rate, with
an end point of femoral revision, osteolysis, or stem debonding, was 90.6 percent
(95 percent confidence interval, 0.87 to 0.94). CONCLUSIONS: The prevalence of
revision, osteolysis, and loosening after total hip arthroplasty with the Iowa
femoral component at our institution was higher than that seen in our series of
Harris Precoat stems, which had a survival rate of 98.4 percent (95 percent
confidence interval, 0.97 to 1.00) at ten years with the same end points. The
design of the Iowa stem may make it difficult to achieve a good cement mantle,
and, in combination with the geometry and increased offset of the stem, may
compromise the long-term survival of this cemented femoral component.
PMID- 11005521
TI - The effect of femoral component head size on posterior dislocation of the
artificial hip joint.
AB - BACKGROUND: Posterior dislocation continues to be a relatively common
complication following total hip arthroplasty. In addition to technical and
patient-associated factors, prosthetic features have also been shown to influence
stability of the artificial hip joint. In this study, a dynamic model of the
artificial hip joint was used to examine the influence of the size of the head of
the femoral component on the range of motion prior to impingement and posterior
dislocation following total hip replacement. METHODS: Six fresh cadaveric
specimens were dissected, and an uncemented total hip prosthesis was implanted in
each. Each specimen was mounted in a mechanical testing machine and loaded with
use of a system of seven cables attached to the femur and pelvis that simulated
the action of the major muscle groups crossing the hip joint. The hip was taken
through a range of motion similar to that experienced when rising from a seated
position. The three-dimensional position of the femur at the points of
impingement and dislocation was recorded electronically. The range of joint
motion was tested with prosthetic femoral heads of four different diameters
(twenty-two, twenty-six, twenty-eight, and thirty-two millimeters). RESULTS:
Significant associations were noted between the femoral head size and the degree
of flexion at dislocation in ten (p = 0.001), twenty (p < 0.001), and thirty (p =
0.003) degrees of adduction. Increasing the femoral head size from twenty-two to
twenty-eight millimeters increased the range of flexion by an average of 5.6
degrees prior to impingement and by an average of 7.6 degrees prior to posterior
dislocation; however, increasing the head size from twenty-eight to thirty-two
millimeters did not lead to more significant improvement in the range of joint
motion. The site of impingement prior to dislocation varied with the size of the
femoral head. With a twenty-two-millimeter head, impingement occurred between the
neck of the femoral prosthesis and the acetabular liner, whereas with a thirty
two-millimeter head, impingement most frequently occurred between the osseous
femur and the pelvis. CONCLUSIONS: With the particular prosthesis that was
tested, increasing the diameter of the femoral head component increased the range
of motion prior to impingement and dislocation, decreased the prevalence of
prosthetic impingement, and increased the prevalence of osseous impingement.
CLINICAL RELEVANCE: These results suggest that femoral heads with a twenty-eight
millimeter diameter increase the range of motion after total hip replacement.
This may be beneficial when additional factors compromising joint stability are
encountered.
PMID- 11005522
TI - Calcaneal osteosarcoma associated with Werner syndrome. A case report with
mutation analysis.
PMID- 11005523
TI - Repetitive stress injury: diagnosis or self-fulfilling prophecy?
AB - * The vague definitions of so-called repetitive stress injuries are indicative of
the fact that scientific studies have failed to show that repetitive motion
causes injury. * Given the uncertainty about causation, work-related
musculoskeletal disorders (WRMSDs) is a more readily accepted term to describe
these phenomena. * There is little doubt that most ergonomic interventions
increase comfort in the work environment, which is of great benefit to the
worker. Many proponents of ergonomics assert that the elimination of certain risk
factors related to force, repetition, and posture can prevent or even cure work
related musculoskeletal disorders of the upper extremity. However, there is
little scientific support for this position. * Undue reliance on ergonomics to
treat musculoskeletal disorders, to the exclusion of proper diagnosis and
attention to medical and health risk factors, can have adverse consequences for
the patient. * Science rather than politics and public policy should determine
what causes injury and disease. * The failure of numerous plaintiffs in
litigation regarding repetitive stress injury due to use of computer keyboards is
important because, when judges and lay jurors were presented with both sides of
the issue, they rejected these claims in a forum (the judicial system) that
traditionally compensates individuals bringing so-called mass-tort cases.
PMID- 11005524
TI - Glucosamine and chondroitin were found to improve outcomes in patients with
osteoarthritis.
PMID- 11005525
TI - Manual physical therapy and exercise improved function in osteoarthritis of the
knee.
PMID- 11005526
TI - Tourniquet use during arthroscopy did not adversely affect patient outcomes.
PMID- 11005527
TI - Passive flexion sign: a simple tool for diagnosis of anterior interosseous nerve
injury in children.
PMID- 11005528
TI - Residency training.
AB - R. C. is an orthopaedic resident in a teaching program. At the orthopaedic
clinic, he examines an elderly, otherwise healthy patient who requires a total
hip replacement. He presents the patient to his covering attending physician, who
agrees to supervise the joint replacement surgery. The resident discusses the
surgery with the patient. The procedure, risks, goals, benefits, and alternatives
are presented. The patient agrees to proceed with the surgery. The resident
performs the surgical procedure with the attending physician's assistance. The
surgery lasts forty minutes longer than the attending physician's usual surgical
time, and the blood loss is 300 milliliters greater. Postoperative radiographs
demonstrate a well positioned press-fit acetabular component and a cemented
femoral component in 6 degrees of varus.
PMID- 11005529
TI - Bone regrowth after partial amputation for diabetes.
PMID- 11005530
TI - The orthopaedic forum.
PMID- 11005531
TI - The orthopaedic forum.
PMID- 11005532
TI - Effect of disability compensation on patient outcomes.
PMID- 11005533
TI - Giant-cell tumors of long bones.
PMID- 11005534
TI - Sample size and statistical power.
PMID- 11005535
TI - Peer review. The millennium engima: more is less.
PMID- 11005536
TI - Hematoma as a complication of enoxaparin use.
PMID- 11005537
TI - Vesalius's inconstant structures.
PMID- 11005538
TI - Missed posterior fracture-dislocation of the humeral head.
PMID- 11005539
TI - Transglenoid suture technique.
PMID- 11005540
TI - Low propensity of conventional antiepileptic drugs for interaction with felbamate
against maximal electroshock-induced seizures in mice.
AB - The objective of this study was to evaluate an interaction of the novel
antiepileptic drug felbamate (2-phenyl-1,3-propanediol dicarbamate) with
conventional antiepileptic drugs against maximal electroshock-induced convulsions
in mice. Electroconvulsions were produced by means of an alternating current (ear
clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the
endpoint). Adverse effects were evaluated in the chimney test (motor performance)
and passive avoidance task (long-term memory). Brain and plasma levels of
antiepileptic drugs were measured by immunofluorescence. Felbamate (7.5-30 mg/kg)
significantly increased the electroconvulsive threshold. Felbamate at the
subprotective dose of 5 mg/kg did not affect the anticonvulsive action of
antiepileptics studied. On the other hand, this drug used at the lowest
protective dose of 7.5mg/kg remained without effect upon the activity of
valproate, carbamazepine or phenobarbital, but significantly potentiated the
protective potential of diphenylhydantoin. No adverse effects were observed with
combinations of felbamate with these antiepileptics. Neither brain nor free
plasma levels of antiepileptic drugs were changed by felbamate. The results
indicate that the combination of felbamate with conventional antiepileptic drugs
is not promising from the experimental point of view.
PMID- 11005541
TI - Nitric oxide synthase does not mediate neurotoxicity after an i.c.v. injection of
streptozotocin in the rat.
AB - In the present study we evaluated the possible role of nitric oxide (NO) in
mediating neuronal damage in middle-aged rats after an i.c.v. injection of
streptozotocin (STREP). An i.c.v. injection of STREP has been reported to
decrease the central metabolism of glucose. This inhibition of the energy
metabolism after STREP treatment might induce an excitotoxic mechanism, which may
lead to the stimulation of NO synthase and, consequently to the synthesis of NO.
On the other hand, STREP might induce oxidative stress directly by liberation of
NO from its nitroso moiety. To investigate whether NO synthase is involved in a
possible excitotoxic mechanism after STREP treatment, some of the rats treated
with STREP (1.25 mg/ kg in 4 microl, bilaterally 2 microl/injection site) were
also treated with the NO synthase inhibitor N-nitro-L-arginine methyl ester (L
NAME, 20 mg/kg i.p. 10 min, 6, 24 and 96 h after STREP injection). To investigate
whether NO liberated from STREP may be responsible for neurotoxic effects, one
additional group of control rats received an i.c.v. injection of the NO donor
sodium nitroprusside (SNP, 10 microg in 4 microl). We found that STREP affected
the behavioral performances in the open field and two-way active avoidance task.
In addition, immunostaining for glial fibrillary acidic protein, an indicator of
reactive astroglial changes to neuronal damage, showed that this was mainly
located in peri- and paraventricular regions of the third and lateral ventricles,
like for instance in the septum, caudate putamen and hippocampus. L-NAME
treatment had no protective effect on the behavioral impairments and neuronal
damage of STREP-treated rats. This suggests that the neuronal damage of STREP may
still be a result of the decrease in the central energy metabolism, but without
the involvement of NO synthase. This was supported by measuring, using
immunostaining, the NO-mediated cyclic GMP production by the enzyme soluble
guanylyl cyclase in cortical slices, i.e. L-NAME did not prevent NO production
after STREP administration in vitro. In addition, it was found that SNP liberated
NO in vitro, whereas in vivo SNP administration did not lead to any behavioral
and neuronal deficits at all. However, the present study cannot exclude the
involvement of NO liberated from STREP in neuronal damage.
PMID- 11005542
TI - Serotonin and sexual behavior in the male rabbit.
AB - Sexual behavior was evaluated in sexually experienced male rabbits after the
administration of different serotonergic drugs. The serotonin1A receptor agonist
8-OH-DPAT, 1 mg/kg, inhibited male rabbit sexual behavior when animals were
tested 15 min after subcutaneous (SC) administration of this compound. Lower
doses, 0.25 and 0.5mg/kg, were ineffective at a test 30 min after drug injection.
Furthermore, 8-OH-DPAT, 0.25mg/kg, failed to revert the inhibitory effects upon
sexual behavior produced by lidocaine application to the rabbit penis.
Stimulation of 5-HT1B/2C receptors by TFMPP, at doses between 0.625 and 2.5
mg/kg, produced a drastic inhibition of sexual behavior when the drug was
administered SC 30 min before behavioral observation. Doses below 5mg/kg were
ineffective when given intraperitoneally 15 min before test. When the 5-HT1D/2C
receptors were stimulated by the agonist mCPP a reduced number of mounts and
ejaculations was observed after the SC administration of 1.25 and 2.5 mg/kg.
Similarly, the mixed 5-HT agonist/antagonist lisuride reduced the percentage of
rabbits displaying mounting behavior at doses of 0.25 and 0.5 mg/kg SC. All
compounds tested produced a clear inhibition of male rabbit sexual behavior
independently of the receptor subtype activated. These results are at variance
with previous observations in rats where 8-OH-DPAT and lisuride produced a
drastic facilitation of masculine coital behavior. Moreover, while the inhibition
of male sexual behavior in rats produced by TFMPP and mCPP is associated with a
disruption of the execution of this behavior, in rabbits these compounds reduced
sexual motivation. These results indicate that the effects of serotonergic drugs
on sexual behavior are species specific.
PMID- 11005544
TI - P300 component of visual event-related potentials distinguishes patients with
idiopathic parkinson's disease from patients with essential tremor.
AB - A considerable rate of misdiagnosis has recently been reported in movement
disorders. One of the most difficult clinical problems is the differentiation of
Parkinson's disease and essential tremor. In this study, we have examined whether
event-related potentials (ERPs) could aid in the solution of this differential
diagnostic problem. Visual ERPs were obtained by using an "oddball" paradigm in
20 patients with idiopathic Parkinson's disease (IPD), 20 patients with essential
tremor (ET), and 20 age-matched control subjects. We found that the P300
amplitudes were selectively reduced in the IPD group at the midline (Fz, Cz, Pz)
electrode sites, whereas the ET group exhibited selectively elevated P300
amplitudes at the left parietal and frontal (F3, P3) recording sites. The
patients with IPD, but not ET, showed a significant prolongation of the P300
latency at each electrode site. Similarly, only the IPD patients were
significantly slower in responding to the target stimulus. The primary visual
evoked potential (P100) did not distinguish among the IPD, ET, and control
subjects. These results suggest that visual ERPs might provide a useful
diagnostic method for differentiating IPD from ET.
PMID- 11005543
TI - The neuroprotective effects of (-)deprenyl in the gerbil hippocampus following
transient global ischemia.
AB - (-)Deprenyl (selegeline) is a monoamine oxidase B (MAO-B) inhibitor, but it also
exerts several effects independent of MAO-B inhibition. For example, it has been
shown to improve neuronal survival in different neurodegenerative models. In the
present study, we have tested whether (-)deprenyl attenuates the neuronal damage
in the hippocampus that is induced in a model of transient global ischemia in
gerbils. (-)Deprenyl was administered 1) at a low daily dose starting two weeks
before occlusion, 2) at a single high dose administered 3h after occlusion, or 3)
at a low daily dose for one or two weeks after occlusion. A nonsignificant trend
of reduced neuronal damage in the hippocampal CA1 area was seen in all
experimental groups treated with (-)deprenyl, regardless of the timing of
treatment. The results together with previous evidence suggest that (-)deprenyl
may protect CA1 neurons from ischemia-induced delayed death by several possible
mechanisms, including the suppression of oxidative stress and apoptotic
processes.
PMID- 11005545
TI - Naturally occurring and experimentally induced beta-amyloid deposits in the
brains of marmosets (Callithrix jacchus).
AB - Cerebral beta-amyloid occurs in elderly animals of some species and in
Alzheimer's disease. Previously, we injected 3 young marmosets intracerebrally
with brain tissue from a patient with Alzheimer's disease. Six years later, when
the monkeys were middle aged, we found moderate numbers of intracerebral plaques
and cerebrovascular deposits containing beta-amyloid. We have re-examined these
brains and those of 10 other marmosets injected with brain homogenate containing
beta-amyloid, and have found some beta-amyloid in animals injected more than 4
years previously. We have found beta-amyloid in 4 of 26 elderly control
marmosets, but not in 9 young to middle-aged control marmosets. The beta-amyloid
found in middle aged marmosets injected with Alzheimer brain tissue was,
therefore, not a consequence of their age. Deposits in large cerebral vessels in
elderly marmosets, and in marmosets previously injected with brain tissue
containing beta-amyloid, reacted with antibodies to Abeta and Abeta1-40; plaques
and microvessel deposits reacted with antibodies to Abeta and Abeta1-42.
PMID- 11005546
TI - Sustained improvements in patients with dementia of Alzheimer's type (DAT) 6
months after termination of Cerebrolysin therapy.
AB - The present study is an extension of the work of Ruther et al. (1994). 101
patients suffering from DAT were evaluated 6 months after completion of a 4 week
(5 days per week) therapy with either 30 ml Cerebrolysin or placebo. The
significant and clinically relevant improvements in the global rating (CGI),
clinical symptomatology (SCAG), cognitive performance (ZVT-G) as primary efficacy
variables, as well as the improvements in the secondary efficacy variables
activities of daily living (NAI) and wellbeing (Bf-S), achieved in the
Cerebrolysin group after only 4 weeks of active therapy, were maintained to a
large extent during the follow-up period. Although there was a moderate tendency
in the drug group towards loss of improvement, the differences between baseline
and follow-up examination, as well as the differences between the verum and the
placebo group, clearly document a sustained improvement in patients treated with
Cerebrolysin in the first 4 weeks of the study period. It can be speculated that
relatively short treatment courses with Cerebrolysin in patients suffering from
neurodegenerative dementia can lead to long term influence on disease
progression, which is in accordance with the proposed neurotrophic - nerve growth
factor like - mode of action.
PMID- 11005547
TI - Salivary, total plasma and plasma free cortisol in panic disorder.
AB - BACKGROUND: Research on basal HPA axis activity in patients with panic disorder
showed inconsistent results. METHODS: Basal total plasma, plasma free and
salivary cortisol levels were compared in patients with panic disorder (n = 47)
and in healthy individuals (n = 23). Correlations between these fractions were
calculated. RESULTS: All three basal cortisol fractions were significantly
elevated in patients compared to controls. There were significant correlations
between all three cortisol fractions. CONCLUSIONS: Nonsignificant differences
between cortisol levels of patients and healthy controls in previous studies may
have been due to inclusion of less severely ill patients or to small sample sizes
(96 words).
PMID- 11005548
TI - Vitamin D in schizophrenia, major depression and alcoholism.
AB - 25-Hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, calcium, phosphate and
parathyreoidal hormone levels were assessed in 34 patients with schizophrenia
(DSM-III-R, 44% female, mean age 38.9 +/- 2.1 years), 30 patients with alcohol
addiction (16% female, mean age 48.7 +/- 2.2 years), 25 patients with major
depression (56% female, mean age 57.6+/- years) and 31 healthy controls. Only 25
hydroxyvitamin D3 and 1,25-dihydroxvitamin D3 levels were significantly lower in
all groups of psychiatric patients than in normal controls, but not phosphate,
calcium and parathyreoidal hormone levels. Significant differences in the vitamin
D levels could not be found between the three psychiatric groups. These findings
do not support the idea that vitamin D is specifically involved in the
pathophysiology of depression. The difference in patients as compared to the
healthy controls might be related to a different social background resulting in
differing habits e.g. of nutrition.
PMID- 11005549
TI - Stability of CSF metabolites measured by proton NMR.
AB - Analysis of cerebrospinal fluid (CSF) metabolites can provide data regarding CNS
involvement in neurologic and psychiatric illness. However, there is lack of
research into the effect of processing and storage of CSF specimens on the levels
of metabolites analyzed. CSF specimens from 10 depressed patients were analyzed
by proton NMR before and after 72 hours exposure to room temperature. No effect
of exposure was found on myoinositol, glucose, acetate, and alanine CSF levels
and there was a substantial decrease of citrate (>50%) and increase in lactate,
glutamine, creatine, and creatinine levels.
PMID- 11005550
TI - Adjuvant radiation after lymph node dissection for melanoma.
PMID- 11005551
TI - Breast conservation without irradiation for invasive disease: legendary quest or
definable reality?
PMID- 11005552
TI - Is adjuvant radiotherapy necessary after positive lymph node dissection in head
and neck melanomas?
AB - INTRODUCTION: Postoperative radiotherapy (PR) has been recommended in patients
with advanced head and neck melanomas to improve regional control. This study
examined the incidence of cervical recurrence among patients who did not receive
PR after surgical management of node-positive head and neck melanomas. METHODS: A
computerized search of a database listing more than 10,000 patients with melanoma
prospectively acquired between 1971 and 1998 identified 217 patients with
pathologically positive nodes who had undergone regional lymph node dissection
(RLND). Of these patients, 21 had received PR and 196 had not. RESULTS: Median
follow-up after RLND was 20 months for nonsurvivors and 32 months for survivors.
The overall incidence of cervical recurrence was 14% (27/196). The 5-year
cervical recurrence-free survival rate was 83%. Five-year cervical recurrence
free survival rates were 69% vs. 87% for patients with vs. without extranodal
disease (P = .004), 96% vs. 81% for patients with nonpalpable vs. palpable nodes
(P = .0761), and 82% vs. 91% for patients with one to three positive nodes vs.
more than three positive nodes (P = .256). Multivariate analysis, which included
the timing of nodal disease presentation and the effect of systemic adjuvant
therapy, identified extranodal disease as the only independent predictor of
cervical recurrence (P = .034). Cervical recurrence was significantly related to
the subsequent occurrence of distant relapse. CONCLUSIONS: The low incidence of
cervical recurrence after RLND in patients with node-positive head and neck
melanomas does not justify the routine use of PR. The only subset of patients who
may benefit from PR are those with extranodal disease.
PMID- 11005553
TI - Factors associated with local breast cancer recurrence after lumpectomy alone:
postmenopausal patients.
AB - BACKGROUND: We have been following a cohort of patients who underwent a
lumpectomy without receiving adjuvant radiotherapy or adjuvant systemic therapy.
We now report the experience of a postmenopausal subgroup. METHODS: The
postmenopausal subgroup included 244 patients accrued between 1977 and 1986 and
followed up. The end point was ipsilateral local breast cancer recurrence. The
factors studied were the patient's age in years; tumor size (in mm); nodal status
(N-, Nx, N+); estrogen and progesterone receptor status (< 10, - 10 fmol/mg
protein); presence or absence of lymphovascular/perineural invasion; presence or
absence, and type, of DCIS (none, non-comedo, comedo); percentage of DCIS;
histological grade (1,2,3); and nuclear grade (1,2,3). Univariate analyses
consisted of Kaplan-Meier plots and the Wilcoxon (Peto-Prentice) test statistic;
the multivariate analyses were step-wise Cox and log-normal regressions. RESULTS:
The median follow-up of those patients still alive was 9.1 years, and the overall
relapse rate was 24% (59/244). The univariate results indicated that the
characteristics of smaller tumor size, negative nodes, positive ER status, and no
lymphovascular or perineural invasion were associated with significantly (P <.05)
lower relapse. From the multivariate analyses, the factors lymphovascular or
perineural invasion, age, and amount of DCIS were all significantly associated
with local relapse with both Cox and log-normal regressions. Additionally, there
was weak evidence of an association between ER (P = .08 in the Cox regression and
in the log-normal) and nodal status (P = .09 in the log-normal regression) with
local relapse. We also are able to define a low-risk subgroup (N-, age -65, no
comedo, ER positive, no emboli) with a crude 10-year local recurrence rate of 9%.
CONCLUSION: With longer follow-up, and for postmenopausal patients, there
continues to be support for the theory that local relapse is affected by the
factors lymphovascular or perineural invasion, age, amount of DCIS, ER, and nodal
status. A low risk subgroup has been identified.
PMID- 11005554
TI - Symposium overview: estrogens and antiestrogens in managing the patient with
breast cancer.
AB - The prevalence of breast cancer (a hormonally driven neoplasm) in the United
States, the potential health benefits of estrogen replacement therapy for
postmenopausal women, and the burgeoning research focusing on selective estrogen
receptor modulators (SERMs) have resulted in additional complexity in managing
breast cancer. In an attempt to clarify existing data, the Society of Surgical
Oncology sponsored a symposium entitled "Estrogens and Antiestrogens in Managing
the Patient with Breast Cancer" at its 52nd Annual Cancer Symposium. This
conference was held in March 1999 and was chaired by Dr. S. Eva Singletary,
Professor of Surgery and Chief of the Surgical Breast Section at The University
of Texas M. D. Anderson Cancer Center in Houston, Texas. The following is a
review of the material presented by the symposium participants.
PMID- 11005555
TI - Impact of sentinel lymph node mapping on relative charges in patients with early
stage breast cancer.
AB - BACKGROUND: The introduction of SLNB has allowed accurate staging in early-stage
breast carcinomas and has minimized the number of unnecessary ALNDs.
Intraoperative frozen-section analysis is a fundamental component of the sentinel
lymph node biopsy (SLNB) procedure. Some patients have positive nodes on frozen
section analysis and thus undergo a conventional axillary lymph node dissection
(ALND) at the time of the SLNB. A few patients have negative nodes on frozen
section analysis but have subsequent evidence of metastases on final pathologic
examination. The purpose of our study was 2-fold: to compare the hospital-related
charges of patients undergoing staging by SLNB with those of patients undergoing
conventional ALND and to assess whether the different outcomes associated with
SLNB adversely affect the charges incurred with this procedure. METHODS: Our
study group consisted of 100 patients with T1 breast cancer and breast
conservation therapy who underwent either SLNB or ALND from July 1, 1997, to June
30, 1998. We identified the first 50 consecutive patients to undergo SLNB during
this period. We chose a similar cohort of 50 patients for ALND. Mean hospital
related charges for the SLNB patients were categorized and compared with those
for the ALND patients. RESULTS: Results for the two groups were analyzed using a
two-sample Wilcoxon rank-sum test. Charges for the OR and hospital stay were less
for the SLNB group (P < .05). Frozen-section analysis in the SLNB group
contributed to the significant difference in charges for pathologic evaluation.
Overall, the two groups showed no significant difference in total hospital
related charges. CONCLUSIONS: When SLNB is used for T1 tumors, a small percentage
of patients (10% in our study) will return to the operating room for an ALND.
This small percentage does not increase the charges related to SLNB, however, as
the reduced stay for most patients offsets this subgroup's contribution to the
total hospital-related charges. Thus, in patients with clinical stage I breast
cancer, SLNB does not cause significantly higher hospital-related charges
compared with conventional ALND.
PMID- 11005556
TI - Impact of multicentricity on clinical outcome in patients with T1-2, N0-1, M0
breast cancer.
AB - BACKGROUND: The objective was to determine the impact of multicentric breast
cancer on recurrence and survival and to evaluate the current tumor, node,
metastasis staging system recommendations for multicentricity in the breast.
METHODS: This study included 284 nonpregnant patients with T1-2, N0-1, M0 breast
cancer, without previous cancer, who were treated by modified radical mastectomy
followed by doxorubicin-based adjuvant chemotherapy. Clinical and pathological
data were collected retrospectively and survival was calculated from the date of
initial diagnosis using the Kaplan-Meier method. RESULTS: The median follow-up
time was 8 years (range, 0.3-24.0), and the median age was 47 years (range, 23
76). The median clinical size of the index tumor was 2.5 cm. In 17% of patients,
the clinical nodal status was N1. In 84% of patients, pathology of the index
lesion was invasive ductal +/- in situ. Multicentric breast cancer was detected
in 60 patients (21%): 30 patients with two lesions, 13 patients with three
lesions, and 17 patients with four or more lesions. Locoregional recurrence,
contralateral breast cancer, distant metastasis, and survival (disease-specific
and disease-free) were similar in both groups of multicentric versus unicentric
breast tumors. There was a significant difference between groups in estrogen
receptor and axillary lymph node positivity, but these did not contribute
significantly to outcome on multivariate analysis. CONCLUSIONS: Multicentricity
does not increase the risk of poor outcomes in patients with early-stage breast
cancer. This supports the current recommendations of the tumor, node, metastasis
staging system that tumor size should be based on the diameter of the largest
lesion in patients with multicentric breast cancer.
PMID- 11005557
TI - A prospective phase II trial of ONYX-015 adenovirus and chemotherapy in recurrent
squamous cell carcinoma of the head and neck (the Baylor experience).
AB - BACKGROUND: The E1-b attenuated adenovirus, ONYX-015 (Onyx Pharmaceuticals,
Richmond, CA), has demonstrated antitumoral activity in patients with recurrent
squamous cell carcinoma of the head and neck. This study evaluated the effects of
intratumoral ONYX-015 injection combined with systemic chemotherapy. METHODS:
Inclusion criteria included: (1) recurrent squamous cell carcinoma of the head
and neck, not surgically salvageable, (2) target tumor amenable to direct
injection, and (3) no prior chemotherapy for recurrent disease. Patients received
ONYX-015 (10(10) plaque-forming units) intratumorally for 5 days, cisplatin (80
mg/m2) on day 1, and 5-fluorouracil (800-1000 mg/m2) on days 1-5. This cycle was
repeated every 3 weeks. Serial physical examination and computed tomography were
used to assess tumor size and treatment response. RESULTS: Fourteen patients were
enrolled, and nine patients were evaluable for response at the time of
enrollment. The mean age of the evaluable patients was 60.8 years (range, 46-71
years). Mean maximum tumor diameter was 4.8 cm (range, 1.9-10.5 cm). Treatment
related toxicity included nausea (n = 7, 77.8%), vomiting (n = 5, 55.6%),
mucositis (n = 5, 55.6%), pain at the injection site (n = 5, 55.6%), constipation
(n = 4, 44.4%), and fatigue (n = 4, 44.4%). Locoregional tumor control was
obtained in all nine patients (100%) (mean observation time, 157 days). Complete
clinical response was seen in three patients (33.3%), partial response was seen
in three patients (33.3%), minor response was seen in one patient (11.1%), and
two patients (22.2%) had stable disease. Median time to local progression of
disease has not been reached (range, 35-356 days). CONCLUSIONS: ONYX-015
adenovirus plus systemic cisplatin and 5-fluorouracil provides antitumor activity
and local tumor control in patients with recurrent squamous cell carcinoma of the
head and neck. This novel treatment approach offers hope for patients with
limited treatment alternatives and provides the foundation for a phase III
clinical trial.
PMID- 11005558
TI - Radiofrequency ablation of 231 unresectable hepatic tumors: indications,
limitations, and complications.
AB - BACKGROUND: Radiofrequency ablation (RFA) is increasingly used for the local
destruction of unresectable hepatic malignancies. There is little information on
its optimal approach or potential complications. METHODS: Since late 1997, we
have undertaken 91 RFA procedures to ablate 231 unresectable primary or
metastatic liver tumors in 84 patients. RFA was performed via celiotomy (n = 39),
laparoscopy (n = 27), or a percutaneous approach (n = 25). Patients were followed
with spiral computed tomographic (CT) scans at 1 to 2 weeks postprocedure and
then every 3 months for 2 years. RESULTS: Intraoperative ultrasound (IOUS)
detected intrahepatic disease not evident on the preoperative scans of 25 of 66
patients (38%) undergoing RFA via celiotomy or laparoscopy. In 38 of 84 patients
(45%), RFA was combined with resection or cryosurgical ablation (CSA), or both.
RFA was used to treat an average of 2.8 lesions per patient, and the median size
of treated lesions was 2 cm (range, 0.3-9 cm). The average hospital stay was 3.6
days overall (1.8 days for percutaneous and laparoscopic cases). Ten patients
underwent a second RFA procedure (sequential ablations) and, in one case, a third
RFA procedure for large (one patient), progressive (seven patients), and/or
recurrent (three patients) lesions. Seven (8%) patients had complications: one
skin burn; one postoperative hemorrhage; two simple hepatic abscesses; one
hepatic abscess associated with diaphragmatic heat necrosis following sequential
percutaneous ablations of a large lesion; one postoperative myocardial
infarction; and one liver failure. There were three deaths, one (1%) of which was
directly related to the RFA procedure. Three of the complications, including one
RFA-related death, occurred after percutaneous RFA. At a median follow-up of 9
months (range, 1-27 months), 15 patients (18%) had recurrences at an RFA site,
and 36 patients (43%) remained clinically free of disease. CONCLUSIONS: Celiotomy
or laparoscopic approaches are preferred for RFA because they allow IOUS, which
may demonstrate occult hepatic disease. Operative RFA also allows concomitant
resection, CSA, or placement of a hepatic artery infusion pump, and isolation of
the liver from adjacent organs. Percutaneous RFA should be reserved for patients
at high risk for anesthesia, those with recurrent or progressive lesions, and
those with smaller lesions sufficiently isolated from adjacent organs.
Complications may be minimized when these approaches are applied selectively.
PMID- 11005559
TI - Lymph node micrometastases do not predict relapse in stage II colon cancer.
AB - BACKGROUND: Over one third of patients with stage II colonic adenocarcinoma
experience tumor recurrence. Because effective adjuvant therapy is now available,
it is important to identify subsets of patients at higher risk for relapse who
may benefit from early treatment. Immunohistochemistry has been used to detect
microscopic metastases in histologically uninvolved mesenteric lymph nodes, but
the prognostic significance of minimal nodal involvement has not been
established. METHODS: Hematoxylin and eosin (H&E)-stained recuts of 900
mesenteric lymph nodes from 55 patients (range, 2-47; mean, 16.4 nodes per case)
with resected pT3 or pT4, N0, M0 (TNM stage II) colonic adenocarcinomas were re
examined for the presence of metastases and then stained immunohistochemically
for keratin using the AE1:AE3 antibody. Twenty-seven patients did not experience
recurrence of tumor within 5 years following resection (no evidence of disease
[NED]); 28 patients relapsed during the same time frame. Lymph nodes from 10
patients having colonic resections for nonneoplastic disorders also were stained
as controls. Keratin-positive cells and cell clusters were quantified in the
lymph nodes, and comparisons were made between patients with and without tumor
relapse. RESULTS: In the relapse group, four patients had positive nodes already
identified on the H&E-stained recuts and had to be excluded from further
analysis. Sixteen additional patients had keratin-positive cells; thus, 16 of 24
(67%) had micrometastases. In the NED group, one patient had a positive node on
H&E staining and 22 additional patients had keratin-positive cells, so 22 of 26
(84%) patients had micrometastases. In the patients who had micrometastases,
there was a mean of 3.5 and 4.6 positive nodes in the relapse and NED groups,
respectively, and a mean of 11.3 and 12.4 keratin-positive cells or clusters in
the relapse and NED groups, respectively. No keratin-positive cells were found in
the 1 to 21 (mean, 9.1) nodes per case studied in the control patients.
CONCLUSIONS: Micrometastases to histologically uninvolved mesenteric lymph nodes
commonly are detected in patients with pT3 or pT4 colonic adenocarcinomas on
recuts stained immunohistochemically for keratin. Nodal micrometastases detected
by immunohistochemical staining are not useful for identifying stage II patients
at higher risk for relapse.
PMID- 11005560
TI - Influence of multimodality therapy on the cellular immunity of patients with
esophageal cancer.
AB - BACKGROUND: Cancer patients have often been reported to have impaired immune
function, and the effect of treatment modalities, such as surgery, irradiation,
and chemotherapy, in depressing patients' immunity has also been reported. In
this investigation, the effect of treatment on the cellular immunity of
esophageal cancer patients was evaluated. METHODS: Immunological parameters, such
as natural killer (NK) activity and lymphocyte subsets in peripheral blood, were
measured in 32 esophageal cancer patients on 5 occasions (on the day of
admission, 2 days before surgery, and 1 week, 1 month, and 2 months after
surgery). RESULTS: NK activity was greatly impaired shortly after the operation,
and the percentages of lymphocytes as a whole, and CD8+, CD16+, and CD57+
lymphocytes were significantly decreased, on the other hand, a postoperative
increase in the CD4+/CD8+ ratio was observed. No significant depression of immune
function by postoperative irradiation was observed. CONCLUSIONS: The results of
this study suggest that cellular immunity, especially cytotoxicity, shortly after
esophagectomy may be greatly impaired by the surgical stress of esophagectomy and
an added effect of chemotherapy.
PMID- 11005561
TI - Preoperative plasma plasminogen activator inhibitor type-1 and serum C-reactive
protein levels in patients with colorectal cancer. The RANX05 Colorectal Cancer
Study Group.
AB - BACKGROUND: Preoperative plasma plasminogen activator inhibitor-1 (PAI-1) is a
prognostic variable in patients with colorectal cancer. It has been suggested,
however, that plasma PAI-1 is a nonspecific prognostic parameter similar to the
acute-phase reactant C-reactive protein (CRP). In the present study we analyzed
the association between plasma PAI-1 and serum CRP in patients scheduled for
elective resection of colorectal cancer. In addition, the prognostic value of PAI
1 and CRP was studied in this patient cohort. METHODS: PAI-1 and CRP were
analyzed in citrated plasma and serum, respectively, obtained preoperatively from
594 patients. Patients who required preoperative blood transfusion received SAGM
blood, in which soluble PAI-1 is not present. None of the patients received pre-
or postoperative adjuvant chemotherapy, and all were followed in the outpatient
clinic for at least 5 years or until death. The association of PAI-1 and CRP,
respectively, with survival was tested using the median value of PAI-1 and the
upper normal limit for CRP. Analyses were performed by inclusion of all patients,
and in the subgroup of patients, who underwent curative resection. RESULTS: The
median follow-up period was 6.8 (5.4-7.9) years. The median value of plasma PAI-1
was 35.8 ng/ml, and values greater than 94 nmol/L identified patients with
increased CRP levels. Comparison of the molecules showed that PAI-1 was weakly
correlated with CRP (r = .26; P <.0001). Both molecules showed a Dukes
independent distribution. In univariate survival analyses high levels of PAI-1
were found associated with poor prognosis and low levels with good prognosis (P =
.02, HR: 1.3). Similarly, high levels of CRP were found associated with poor
prognosis and low levels with good prognosis (P <.0001, HR: 1.9). In a
multivariate statistical analysis including Dukes classification, gender, age,
tumor location, perioperative blood transfusion, PAI-1 and CRP, plasma PAI-1 was
a dependent prognostic variable, while serum CRP (P <.0001; HR: 1.4; 95% CI: 1.3
1.5) was found to be a Dukes independent prognostic variable. Similar analyses,
excluding patients with Dukes' D disease showed serum CRP to be an independent
prognostic variable (P <.0001; HR: 1.3: 95% CI: 1.2-1.5). CONCLUSIONS: This study
did not show a strong correlation between plasma PAI-1 and serum CRP in patients
with colorectal cancer. Serum CRP was found to be a Dukes independent prognostic
variable in this patient cohort, and was found to identify a subgroup of
curatively resected patients at risk for short survival.
PMID- 11005562
TI - Reliability of lymphoscintigraphy in indicating the number of sentinel nodes in
melanoma patients.
AB - BACKGROUND: This study was undertaken to establish the reliability of
lymphoscintigraphy in indicating the number of sentinel nodes in patients with
melanoma. METHODS: Lymphoscintigraphy was performed with dynamic imaging after
injection of 60 MBq 99mTc-nanocolloid (1.6 mCi) and static imaging after 2 hours
in 200 patients with clinically localized primary melanoma of the skin. The
following day, sentinel nodes were retrieved with the blue dye technique and a
gamma detection probe (Neoprobe 1000/1500). The discrepancies between the number
of sentinel nodes indicated by lymphoscintigraphy and the actual number of
sentinel nodes as established by the surgeon were evaluated. RESULTS:
Lymphoscintigraphy showed drainage to 393 sentinel nodes in 255 lymphatic fields
in 199 patients. In 48 lymphatic fields (19%) in 46 patients (23%), the number of
sentinel nodes was different from the number that was visualized with
scintigraphy. Additional sentinel nodes were found by the surgeon because a
lymphatic vessel was not seen on the lymphoscintigraphy (43%), because a sentinel
node was not visualized separately from other hot nodes or vessels or the
injection site (36%), or because a sentinel node was blue and not hot (4%). Fewer
sentinel nodes were found than suggested by scintigraphy because a lymphangioma
was mistaken for a sentinel node (4%) or because a single elongated node was
depicted as two hot spots (6%). CONCLUSIONS: Although lymphoscintigraphy is
indispensable for lymphatic mapping, the predicted number of sentinel nodes is
accurate in only 81% of lymph node fields. The limited discriminating power of
the gamma camera is an important cause of discrepancies.
PMID- 11005563
TI - Cell cycle and apoptosis.
AB - In multicellular organisms, cell proliferation and death must be regulated to
maintain tissue homeostasis. Many observations suggest that this regulation may
be achieved, in part, by coupling the process of cell cycle progression and
programmed cell death by using and controlling a shared set of factors. An
argument in favor of a link between the cell cycle and apoptosis arises from the
accumulated evidence that manipulation of the cell cycle may either prevent or
induce an apoptotic response. This linkage has been recognized for tumor
suppressor genes such as p53 and RB, the dominant oncogene, c-Myc, and several
cyclin-dependent kinases (Cdks) and their regulators. These proteins that
function in proliferative pathways may also act to sensitize cells to apoptosis.
Indeed, unregulated cell proliferation can result in pathologic conditions
including neoplasias if it is not countered by the appropriate cell death.
Translating the knowledge gained by studying the connection between cell death
and cell proliferation may aid in identifying novel therapies to circumvent
disease progression or improve clinical outcome.
PMID- 11005564
TI - Mutation and expression of the DCC gene in human lung cancer.
AB - Chromosome 18q is frequently deleted in lung cancers, and a common region of 18q
deletions was mapped to chromosome 18q21. Since the DCC candidate tumor
suppressor gene has been mapped in this region, mutation and expression of the
DCC gene were examined in 46 lung cancer cell lines, consisting of 14 small cell
lung carcinomas (SCLCs) and 32 non-small cell lung carcinomas (NSCLCs), to
elucidate the pathogenetic significance of DCC alterations in human lung
carcinogenesis. A heterozygous missense mutation was detected in a NSCLC cell
line, Ma26, while homozygous deletion was not detected in any of the cell lines.
The DCC gene was expressed in 11 (24%) of the 46 cell lines, and the incidence of
DCC expression was significantly higher in SCLCs (7/14, 50%) than in NSCLCs
(4/32, 13%) (P = .01, Fisher's exact test). Therefore, genetic alterations of DCC
are infrequent; however, the levels of DCC expression vary among lung cancer
cells, in particular, between SCLCs and NSCLCs. The present result does not
implicate DCC as a specific mutational target of 18q deletions in human lung
cancer; however, it suggests that DCC is a potential target of inactivation by
genetic defects including intron or promoter mutations and/or epigenetic
alterations. The present result also suggests that DCC expression is associated
with some properties of SCLCs, such as a neuroendocrine (NE) feature.
PMID- 11005565
TI - Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in
increased vascular cooption.
AB - Vascular endothelial growth factor (VEGF) is an important mediator of the intense
angiogenesis which is characteristic of glioblastoma. While genetic manipulation
of VEGF/VEGF receptor expression has previously been shown to inhibit
glioblastoma growth, to date, no study has examined the efficacy of pharmacologic
blockade of VEGF activity as a means to inhibit intracranial growth of human
glioblastoma. Using intraperitoneal administration of a neutralizing anti-VEGF
antibody, we demonstrate that inhibition of VEGF significantly prolongs survival
in athymic rats inoculated in the basal ganglia with G55 human glioblastoma
cells. Systemic anti-VEGF inhibition causes decreased tumor vascularity as well
as a marked increase in tumor cell apoptosis in intracranial tumors. Although
intracranial glioblastoma tumors grow more slowly as a consequence of anti-VEGF
treatment, the histologic pattern of growth suggests that these tumors adapt to
inhibition of angiogenesis by increased infiltration and cooption of the host
vasculature.
PMID- 11005566
TI - Solitary lung tumors and their spontaneous metastasis in athymic nude mice
orthotopically implanted with human non-small cell lung cancer.
AB - We examined the tumorigenic and metastatic potentials of three human non-small
cell lung cancer (NSCLC) cell lines, PC-14, A549 or Lu-99 cell lines suspended in
Matrigel-containing phosphate-buffered saline were orthotopically implanted into
the lungs of nude mice. The formation of a solitary tumor nodule in the lung was
observed after the implantation of all cell lines. Intrapulmonary implantation of
PC-14 or Lu-99 cells resulted in spontaneous distant metastases. In contrast,
A549 cells caused multiple intrapulmonary metastases to the right and left lobes
of the lung without producing visible lymphatic metastasis. We also investigated
the expression of matrix metalloproteinases (MMPs), urokinase-type plasminogen
activator (u-PA), u-PA receptor (u-PAR) and c-MET in these cell lines in vitro
and in vivo. Reverse transcription polymerase chain reaction (RT-PCR) analysis
showed that the expression of MMP-2 and membrane-type 1 MMP (MT1-MMP) was
elevated in PC-14 as compared with the other two cell lines. In contrast,
stronger expression of c-MET was observed in A549 than in PC-14 or Lu-99. These
results indicate that differential patterns of metastasis of lung cancer might be
associated with differential expression of metastasis-associated molecules. Our
orthotopic implantation models display clinical features resembling those of
NSCLC, and may provide a useful basis for lung cancer research.
PMID- 11005567
TI - A mathematical model for comparison of bolus injection, continuous infusion, and
liposomal delivery of doxorubicin to tumor cells.
AB - Determining the optimal mode of delivery for doxorubicin is important given the
wide use of the drug against many tumor types. The relative performances of bolus
injection, continuous infusion, liposomal and thermoliposomal delivery are not
yet definitely established from clinical trials. Here, a mathematical model is
used to compare bolus injection, continuous infusion for various durations,
liposomal and thermoliposomal delivery of doxorubicin. Effects of the relatively
slow rate, and saturability, of doxorubicin uptake by cells are included. Peak
concentrations attained in tumor cells are predicted and used as a measure of
antitumor effectiveness. To measure toxicity, plasma area under the curve (AUC)
and peak plasma concentrations of free doxorubicin are computed. For continuous
infusion, the duration of infusion significantly affects predicted outcome. The
optimal infusion duration increases with dose, and is in the range 1 to 3 hours
at typical doses. The simulations suggest that continuous infusion for optimal
durations is superior to the other protocols. Nonthermosensitive liposomes
approach the efficacy of continuous infusion only if they release drug at optimal
rates. Predictions for thermosensitive liposomes indicate a potential advantage
at some doses, but only if hyperthermia is applied locally so that the blood is
not significantly heated.
PMID- 11005568
TI - Caspase-dependent apoptosis induced by telomere cleavage and TRF2 loss.
AB - Chromosomal abnormalities involving telomeric associations (TAs) often precede
replicative senescence and abnormal chromosome configurations. We report here
that telomere cleavage following exposure to proapoptotic agents is an early
event in apoptosis. Exposure of human and murine cancer cells to a variety of pro
apoptotic stimuli (staurosporine, thapsigargin, anti-Fas antibody, and cancer
chemotherapeutic agents) resulted in telomere cleavage and aggregation, and
finally their extrusion from the nuclei. Telomere loss was associated with arrest
of cells in G2/M phase and preceded DNA fragmentation. Telomere erosion and
subsequent large-scale chromatin cleavage were inhibited by overexpression of the
anti-apoptotic protein, bcl-2, and two peptide caspase inhibitors (BACMK and
zVADfmk), indicating that both events are regulated by caspase activation. The
results demonstrate that telomere cleavage is an early chromatin alteration
detected in various cancer cell lines leading to drug-induced apoptosis, and
suggest that this event contributes to mitotic catastrophe and induction of cell
death. Results also suggest that the decrease of telomeric-repeat binding factor
2 (TRF2) may be the earliest event in the ara-C-induced telomere shortening,
induction of endoreduplication and chromosomal fragmentation leading to cell
death.
PMID- 11005569
TI - Indomethacin-induced apoptosis in esophageal adenocarcinoma cells involves
upregulation of Bax and translocation of mitochondrial cytochrome C independent
of COX-2 expression.
AB - The prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown
to exert a chemopreventive effect in esophageal and other gastrointestinal
tumors. The precise mechanism by which this occurs, however, is unknown. While
the inhibition of COX-2 as a potential explanation for this chemopreventive
effect has gained a great deal of support, there also exists evidence supporting
the presence of cyclooxygenase-independent pathways through which NSAIDs may
exert their effects. In this study, immunohistochemical analysis of 29 Barrett's
epithelial samples and 60 esophageal adenocarcinomas demonstrated abundant
expression of the COX-2 protein in Barrett's epithelium, but marked heterogeneity
of expression in esophageal adenocarcinomas. The three esophageal adenocarcinoma
cell lines, Flo-1, Bic-1, and Seg-1, also demonstrated varying expression
patterns for COX-1 and COX-2. Indomethacin induced apoptosis in all three cell
lines, however, in both a time- and dose-dependent manner. In Flo-1 cells, which
expressed almost undetectable levels of COX-1 and COX-2, and in Seg-1, which
expressed significant levels of COX-1 and COX-2, indomethacin caused upregulation
of the pro-apoptotic protein Bax. The upregulation of Bax was accompanied by the
translocation of mitochondrial cytochrome c to the cytoplasm, and activation of
caspase 9. Pre-treatment of both cell lines with the specific caspase 9
inhibitor, z-LEHD-FMK, as well as the broad-spectrum caspase inhibitor, z-VAD
FMK, blocked the effect of indomethacin-induced apoptosis. These data demonstrate
that induction of apoptosis by indomethacin in esophageal adenocarcinoma cells is
associated with the upregulation of Bax expression and mitochondrial cytochrome c
translocation, and does not correlate with the expression of COX-2. This may have
important implications for identifying new therapeutic targets in this deadly
disease.
PMID- 11005572
TI - Polymer-supported and chemoenzymatic synthesis of the Neisseria meningitidis
pentasaccharide: a methodological comparison.
AB - Neisseria meningitidis trisaccharide [GlcNAc[(1-->3)Galbeta(1-->4)Glc-R],
tetrasaccharide [Galbeta(1-->4)GlcNAcbeta(1--> 3)Galbeta(1-->4)Glc-R], and a
pentasaccharide [Neu5Acalpha(2-->3)Galbeta(1-->4)GlcNAcbeta(1-->3)G albeta(1-
>4)Glc-SPh] were prepared via conventional chemical synthesis, polymer-supported
synthesis, and chemoenzymatic methods, starting from D-lactose. The polymer
polyethyleneglycol monomethylether (MPEG) and the linker dioxyxylene (DOX) were
used with a lactose-bound acceptor to improve the purification process. Several
enzymes (LgtA, GalE-LgtB fusion, and CMP-Neu5Ac synthetase/sialyltransferase
fusion) were used for syntheses of these oligosaccharides. Excellent stereo- and
regioselectivities as well as high yield (> 90% from Gal(1-->4)Glc-SPh) of the
pentasaccharide were obtained. Both of the convenient processes are suitable for
efficient preparation of target oligosaccharides.
PMID- 11005570
TI - Ras-mediated suppression of TGFbetaRII expression in intestinal epithelial cells
involves Raf-independent signaling.
AB - Ras-transformed intestinal epithelial cells are resistant to the growth
inhibitory actions of TGFbeta and have a marked decrease in expression of the
TGFbeta type II receptor (TGFbetaRII). Rat intestinal epithelial cells (RIE) were
stably transfected with activated Ras, Sos and Raf constructs and tested for
expression of TGFbetaRII and sensitivity to growth inhibition by TGFbeta. The
parental RIE line and the RIE-Raf cells were non-transformed in morphology and
were sensitive to TGFbeta (70-90% inhibited). In contrast, the RIE-Ras and RIE
Sos lines were transformed, resistant to TGFbeta and expressed 5- to 10-fold
decreased levels of the TGFbetaRII mRNA and protein. Cyclin D1 protein expression
was repressed by TGFbeta treatment in parental RIE and RIE-Raf cells, whereas
levels of cyclin D1 in RIE-Ras and RIE-Sos cells remained unchanged. Treatment of
RIE-Ras cells with 25 microM farnesyl transferase inhibitor, FTI L739,749, for 48
hours restored expression of TGFbetaRII to levels equivalent to control cells. In
addition, treatment of RIE-Ras cells for 48 hours with PD-98059, a specific MAPKK
inhibitor, also increased expression of TGFbetaRII to control levels.
Collectively these results suggest that downregulation of TGFbetaRII and loss of
sensitivity to growth inhibition by TGFbeta in Ras-transformed intestinal
epithelial cells is not mediated exclusively by the conventional
Ras/Raf/MAPKK/MAPK pathway. However, activation of MAPK, perhaps by an alternate
Ras effector pathway, appears to be necessary for Ras-mediated downregulation of
TGFbetaRII.
PMID- 11005571
TI - HGF/SF activates glycolysis and oxidative phosphorylation in DA3 murine mammary
cancer cells.
AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine growth factor
which increases cellular motility and has also been implicated in tumor
development and progression and in angiogenesis. Little is known about the
metabolic alteration induced in cells following Met-HGF/SF signal transduction.
The hypothesis that HGF/SF alters the energy metabolism of cancer cells was
investigated in perfused DA3 murine mammary cancer cells by nuclear magnetic
resonance (NMR) spectroscopy, oxygen and glucose consumption assays and confocal
laser scanning microscopy (CLSM). 31P NMR demonstrated that HGF/SF induced
remarkable alterations in phospholipid metabolites, and enhanced the rate of
glucose phosphorylation (P < .05). 13C NMR measurements, using [13C1]-glucose
enriched medium, showed that HGS/SF reduced the steady state levels of glucose
and elevated those of lactate (P < .05). In addition, HGF/SF treatment increased
oxygen consumption from 0.58+/-0.02 to 0.71+/-0.03 micromol/hour per milligram
protein (P < .05). However, it decreased CO2 levels, and attenuated pH decrease.
The mechanisms of these unexpected effects were delineated by CLSM, using NAD(P)H
fluorescence measurements, which showed that HGF/SF increased the oxidation of
the mitochondrial NAD system. We propose that concomitant with induction of
ruffling, HGF/SF enhances both the glycolytic and oxidative phosphorylation
pathways of energy production.
PMID- 11005573
TI - Syntheses of four D- and L-hexoses via diastereoselective and enantioselective
dihydroxylation reactions.
AB - An expeditious approach to various protected hexoses has been developed by the
use of the Sharpless catalytic asymmetric dihydroxylation reaction. Applying the
Sharpless catalytic asymmetric dihydroxylation reaction on vinylfuran, diols with
high enantioexcess are produced. The resulting diols can be stereoselectively
transformed into either protected D- or L-mannose in five steps and approximately
39% yield from furfural. Similarly, both D- and L-talose and gulose have been
synthesized in 19% overall yields, respectively. Using a modified strategy, both
protected D- and L-gulo- and allo-sugar-delta-lactones were synthesized in eight
steps and approximately 20%, overall yield from furfural.
PMID- 11005574
TI - Synthesis of novel 3'-C-methyl-apionucleosides: an asymmetric construction of a
quaternary carbon by Claisen rearrangement.
AB - The synthesis of 2,3-dideoxy-3-C-(hydroxymethyl)-3-C-methyl-D-glycero
tetrofuranosyl++ + nucleosides was accomplished in high enatiomeric purity (98.5%
ee) via [3,3]-sigmatropic Claisen rearrangement of (E)(S)-5-benzyloxy-1-tert
butyldimethylsilanyloxy-4-methyl-pent-3- en-2-ol prepared from 2,3-O
isopropylidene-D-glyceraldehyde. The synthesized nucleosides were assayed against
human immunodeficiency virus (HIV) and hepatitis B virus in human peripheral
blood mononuclear (PBM) and 2.2.15 cells, respectively. 6-Amino-9-[2,3-dideoxy-3
C-(hydroxymethyl)-3-C-methyl-beta-D-glycero- tetrofuranosyl]-2-fluoropurine shows
moderate antiviral activity (EC50 = 2.55 microM) against HIV-1 strains and 6
amino-9-[3-deoxy-3-C-(hydroxymethyl)-3-methyl-alpha-D-glycero-tetro furanosyl]-2
fluoropurine exhibits potent anti-HIV activity (EC50 = 0.073 microM) with
significant cytotoxicity (IC50 = 1.0 microM).
PMID- 11005575
TI - Synthesis of 2',3'-dideoxy-3'-fluoro-L-ribonucleosides as potential antiviral
agents from D-sorbitol.
AB - 2',3'-Dideoxy-3'-fluoro-L-ribonucleosides were synthesized as potential antiviral
agents. The key intermediate, methyl 5-O-benzoyl-2,3-dideoxy-3-fluoro-L
ribofuranoside, which was prepared from D-sorbitol, was condensed with pyrimidine
and purine bases to obtain the respective nucleosides. Among them, the cytosine
analogue 2',3'-dideoxy-3'-fluoro-alpha-L-cytidine showed a moderate anti-HBV
activity.
PMID- 11005576
TI - Selective formation of C-2 azidodeoxy-D-glucose derivatives from D-glucal
precursors using the azidonitration reaction.
AB - A series of glucals, protected by cyclic acetal protecting groups to
conformationally constrain the C-4 and C-6 hydroxyl groups, were subjected to the
azidonitration reaction to furnish the corresponding C-2 azidodeoxy-D-glucoses.
4,6-O-Isopropylidene-3-O-triisopropylsilyl-D-arabino-hex-1-enit ol afforded 2
azido-2-deoxy-4,6-O-isopropylidene-3-O-triisopropylsilyl-D-gluco pyranosyl
nitrate and its D-manno isomer in a 20:1 ratio. These findings allow the
azidonitration reaction to be now used for the preparation of a variety of
glucosamine building blocks from differentially protected glucal precursors.
PMID- 11005577
TI - Synthesis of the HSA-conjugate of the S-linked thiomimetic of the branched
tetrasaccharide repeating unit of the immunostimulant polysaccharide,
schizophyllan. Evaluation as potential immunomodulator.
AB - The conjugate with human serum albumin (HSA) of the S-linked thioanalogue of the
branched tetrasaccharide repeating unit of the polysaccharide, schizophyllan, was
synthesized from 1,2,4,6-tetra-O-acetyl-3-S-[2,4-di-O-acetyl-3,6-di-S-(2,3,4,6
tetra-O-ac etyl-beta-D-glucopyranosyl)-3,6-dithio-beta-D-glucopyranosyl]-3-thio
bet a-D-glucopyranose [M.O. Contour-Galcera et al., Carbohydr. Res., 281 (1996)
119-128] in five steps, and its potential immunomodulatory activity was evaluated
in human blood mononuclear cells. The protein glycoconjugate did not effect
proliferation or production of IL-4, IL-5 and IFN-g in a significant way.
PMID- 11005578
TI - The use of the 2-aminobenzoic acid tag for oligosaccharide gel electrophoresis.
AB - Gel electrophoresis of fluorophore labeled saccharides provides a rapid and
reliable method to screen enzymatic and/or chemical treatments of polysaccharides
and glycoconjugates, as well as a sensitive and efficient microscale method to
separate and purify oligosaccharides for further analysis. A simple and
inexpensive method of derivatization and analysis using 2-aminobenzoic acid
(anthranilic acid, AA) is described and applied to the extracellular
polysaccharide released by the desiccation tolerant cyanobacterium Nostoc commune
DRH-1. The results of these analyses suggest a possible protective functionality
of two pendent groups, as well as a potential relationship between these groups
and the desiccation tolerance of the organism.
PMID- 11005579
TI - Ischemic preconditioning.
PMID- 11005580
TI - Do mitochondrial K(ATP) channels serve as triggers rather than end-effectors of
ischemic preconditioning's protection?
PMID- 11005581
TI - Opening mitochondrial K(ATP) in the heart--what happens, and what does not
happen.
AB - There is considerable evidence that opening the mitochondrial ATP-sensitive
potassium channel (mitoK(ATP)) is cardioprotective in ischemia-reperfusion. Two
prominent questions surround the role of mitoK(ATP) in the cardiomyocyte: How
does opening mitoK(ATP) protect? What is the normal physiological role of
mitoK(ATP) in the heart? Before these questions can be addressed, it is necessary
to agree on the bioenergetic consequences of opening mitoK(ATP), and this
distills down to a single question--does opening mitoK(ATP) cause significant
uncoupling or not? The evidence strongly indicates that it does not and that
reports of uncoupling and inhibition of Ca2+ uptake are the result of using toxic
concentrations of K(ATP) channel openers. Thus, opening mitoK(ATP) results in
increased K+ flux that is sufficient to change mitochondrial volume but is
insufficient to cause significant depolarization of membrane potential. The
volume changes, however, have significant bioenergetic consequences for energy
coupling in the cell.
PMID- 11005582
TI - The role of mitochondrial KATP channels in cardioprotection.
PMID- 11005583
TI - The role of mitochondrial K(ATP) channels in cardioprotection.
PMID- 11005584
TI - Potential role of endothelin-1 and endothelin antagonists in cardiovascular
diseases.
AB - The endothelins comprise a family of three isopeptides ET-1, ET-2 and ET-3,
whereby ET-1 appears to be the most relevant in humans. They act in a paracrine
manner on ETA and ETB receptors. ET-1 plays an important role in the
cardiovascular system. In addition, it modulates vasomotion and growth processes,
and it participates in thrombogenesis and neutrophil adhesion. This review
summarizes some of the current literature pertaining to the physiological and
pathophysiological significance of ET-1, focusing the assets and drawbacks of
elevated ET-1 levels. In this regard, modulation of the endothelin system by
either receptor blockade or by inhibition of endothelin converting enzyme is
expected to provide novel therapeutic drug strategies.
PMID- 11005585
TI - Influence of intercellular junctions on endothelin secretion of human umbilical
vein endothelial cells in vitro.
AB - The endothelium plays a pivotal role in the rheological regulation of blood flow
by the secretion of vasoactive factors. The interaction between shear forces and
the endothelium is determined by the mechanical properties of the endothelial
cell layer which are associated with intercellular junctions. Cell-cell contacts
could therefore modulate the secretion of vasocative factors in response to
rheological stimuli. We investigated the relationship between intercellular
junctions and the secretion of the vasoconstrictor peptide endothelin and the
coagulation co-factor von Willebrand factor (vWF). Human umbilical vein
endothelial cells (HUVECs) were used as in vitro endothelial model system.
Intercellular junctions were reversibly disrupted by calcium chelation or
hypertonic stress; alternatively, the formation of intercellular junctions was
inhibited by culturing the cells in suspension or by plating them in the presence
of an inhibitory anti-VE-cadherin antibody. The opening of intercellular
junctions was verified by assessing transmonolayer electrical resistance (TMR)
and immunofluorescence morphology. The concentration of endothelin and vWF was
measured in the cell culture supernatants using specific ELISAs. The secretion of
endothelin was inhibited by EGTA (5 mM) and stimulated by incubation with tumor
necrosis factor alpha (TNFalpha, 40 ng/ml). Treatment with hypertonic medium
(glycerol, 1,200 mosmol/l) for 10 minutes opened intercellular junctions and
markedly reduced the secretion of endothelin. HUVECs in suspension culture did
not secrete endothelin and failed to respond to TNFalpha, but readily resumed
these functions upon forming a new monolayer on plastic. The reconstitution of
intercellular junctions after suspension culture could be inhibited using a
specific anti-VE-cadherin antibody. This antibody, but not a non-specific anti
human-IgG antibody reduced endothelin secretion. The secretion of von Willebrand
Factor was less dependent on intercellular junctions. The opening of
intercellular junctions did not induce cell death, since the cells continued to
exclude trypan blue. The results of this study suggest a novel and potentially
pathophysiologically/clinically relevant correlation between intercellular
junctions and the secretion of endothelin in endothelial cells.
PMID- 11005586
TI - Lack of nuclear apoptosis in cardiomyocytes and increased endothelin-1 levels in
a rat heart model of myocardial stunning.
AB - OBJECTIVE: Reperfusion injury may affect the cardiac NO and endothelin
production. We investigated whether 20 min of total ischemia followed by 40 min
of reperfusion can induce apoptosis in a Langendorff model of retrogradely
perfused rat hearts (37 degrees C; paced at 300/'), and we attempted to correlate
these findings with measured tissue NO and ET-1 levels. METHODS: An apoptosis
detection system was utilized which catalytically incorporates fluorescein-12
dUTP at the 3'-OH DNA ends using the principle of the TUNEL assay, with direct
visualization of the labeled DNA. ET-1 was measured by radioimmunoassay and
NO3/NO2 by ion pairing HPLC on C18 reverse phase columns. RESULTS: None of the
postischemic (n = 6) nor of the control perfused (90 min, n = 6) hearts showed
signs of apoptosis, while those exposed to longer ischemia (40 min) and
reperfusion (2 h) confirmed the presence of apoptotic cells. Myocardial ET-1
concentrations were 4.8 +/- 1.0 versus 8.3 +/- 2.5 pg/100 mg (control vs.
ischemic hearts, respectively; mean +/- SD; p < 0.05). Myocardial NO contents
showed no differences. CONCLUSION: These data suggest that the time window of
apoptosis with detectable DNA fragmentation exceeds 20 min of global total
ischemia and 40 min of reperfusion, a model frequently used for inducing
myocardial stunning. While NO was not increased in postischemic hearts, increased
ET-1 levels indirectly argue for a role of ET-1 as inducer of apoptosis, but only
at a later stage of reperfusion.
PMID- 11005587
TI - Differences in time course of myocardial mRNA expression in non-infarcted
myocardium after myocardial infarction.
AB - In non-infarcted myocardium after myocardial infarction, the change of cardiac
phenotypic modulation of contractile protein, extracellular matrix and
intracellular Ca2+ transport protein, such as sarcoplasmic reticulum Ca2+(SR
Ca2+)-ATPase, Na+-Ca2+ exchanger, have a important role during cardiac
remodeling. However, the time course in this gene expression in the adjacent and
remote left ventricular, or right ventricular myocardium after myocardial
infarction has not been well examined. The purpose of this study was to examine
the left ventricular function and regional cardiac gene expression after
myocardial infarction. Myocardial infarction was produced in Wistar rats by the
ligation of the left anterior descending coronary artery. After 3 weeks, 2 months
and 4 months from myocardial infarction, we performed Doppler echocardiography
and measured the systolic and diastolic function. Then, we analyzed the
contractile protein, extracellular matrix and intracellular Ca2+ transport
protein mRNAs of cardiac tissues in the adjacent and the remote noninfarcted
myocardium, and right ventricular myocardium by Northern blot hybridization.
Fractional shortening of infarcted heart progressively decreased. Peak early
diastolic filling wave (E wave) velocity increased, and the deceleration rate of
the E wave velocity was more rapid in myocardial infarction areas. Atrial filling
wave (A wave) velocity decreased, resulting in a marked increase in the ratio of
E wave to A wave velocity. Expression of myocardial alpha-skeletal actin, beta
MHC and ANP mRNA, or collagen I and III mRNA were higher at 3 weeks after
myocardial infarction. SR Ca2+-ATPase mRNA in the adjacent non-infarcted
myocardium was decreased at 2 months, and that in remote myocardium was decreased
at 4 months after infarction. Na+-Ca2+ exchanger mRNA levels were increased at 3
weeks, but was decreased at 2 months in the adjacent non-infarcted myocardium and
at 4 months in the remote myocardium. These findings suggest that the
compensation for myocardial infarction by myocardial gene expression in non
infarcted myocardium may occur at an early phase after myocardial infarction, and
myocardial dysfunction may begin from adjacent to remote non-infarcted myocardium
during progressive cardiac remodeling.
PMID- 11005588
TI - Electrophysiologic effects of the new I(Ks)-blocking agent chromanol 293b in the
postinfarction canine heart. Preserved positive use-dependence and preferential
prolongation of refractoriness in the infarct zone.
AB - OBJECTIVES: Aim of the present study was to investigate site- and rate dependent
effects of the IKs-blocking agent chromanol 293b on conduction and refractoriness
in normal, infarcted, and transitional regions of in-situ canine hearts. METHODS:
In five dogs with subacute myocardial infarction, three-dimensional mapping was
performed after insertion of 6 x 6 needle electrodes in the left ventricle.
Before and after application of chromanol 293b (10 mg/kg), activation patterns
and local refractory periods (ERPs) at pacing intervals of 300, 500 and 850 ms
were obtained for the surviving epicardial muscle layer of the infarct zone (IZ)
and for epi-, endo-, and midmyocardial muscle layers of both the normal zone (NZ)
and the border zone (BZ) separating normal and infarcted areas. RESULTS: At
baseline, both the NZ and the BZ exhibited uniform ERPs throughout the
ventricular wall. Epicardial ERPs were longer in the IZ than in the NZ, and
intermediate in the BZ. Chromanol 293b did not affect total activation times.
However, at fast heart rates regional areas of slow conduction occurred.
Chromanol 293b ubiquitously prolonged local ERPs, most markedly in the IZ. A
preferential effect on individual muscle layers of the NZ or BZ and, thus, drug
induced transmural dispersion of ERP could not be observed. Again ubiquitously,
the effect on ERP was more pronounced at faster than at slower heart rates, that
is, positive use-dependent. At a basic cycle length of 300 ms, chromanol 293b
prolonged local ERPs in the IZ by 46 +/- 24 %, in the BZ by 34 +/- 26%, and in
the NZ by 20 +/- 17% (p < or = 0.05). CONCLUSIONS: At least in theory, the
electrophysiologic properties of chromanol 293 b, that is, preferential
prolongation of refractoriness in ischemic myocardium, more pronounced at faster
than at slower heart rates, but homogeneously throughout the intact ventricular
wall, appear to be favorable. Whether this translates into a clinical benefit,
particularly in the treatment of ischemia-related ventricular tachyarrhythmias,
remains to be determined.
PMID- 11005589
TI - Inefficient ventilation and reduced respiratory muscle capacity in congestive
heart failure.
AB - The extent and time-course of changes in lung volumes, ventilatory efficiency at
rest and during exercise, and respiratory muscle function and their influence on
exercise limitation in congestive heart failure (CHF) are unclear. It is unknown
whether respiratory muscle function may predict changes in exercise limitation or
may be impaired in patients with poor outcome. 145 male patients (54 +/- 1 years)
suffering from CHF (NYHA class I-III, mean 2.3 +/- 0.1), with a LVEF of 23 +/-
1%, and a mean peak O2 uptake (VO2peak) 15.0 +/- 0.5 mL X min(-1) X kg(-1), were
studied. They were grouped in Weber functional classes A to D according to their
VO2peak. Significant increases in ventilatory equivalents for O2 and CO2
(VE/VCO2peak) and in dead space ventilation at rest and during exercise were
found with increasing exercise limitation. Moreover, there was a correlation of
static and dynamic lung volumes (inspiratory vital capacity, IVC, r = 0.43, P <
0.01), as well as of maximal inspiratory pressure (MIP; r = 0.46, P < 0.01) with
VO2peak. Patients who died (n = 26) or were heart transplanted (n = 20) during a
follow-up (mean 800 +/- 10 days) had a reduced MIP (6.4 +/- 0.4 kPa) as compared
with survivors (n = 82; 9.3 +/- 0.7 kPa, P < 0.01). In a subgroup of 33 patients
re-evaluated after six months, individual changes in IVC and VE/CO2peak, but not
in MIP, correlated to changes in VO2peak (r = 0.69 and r = 0.72 respectively; P <
0.01). In CHF, exercise limitation is associated with reversible lung restriction
and inefficient ventilation at rest and during exercise. Patients with severe CHF
have a significant reduction in MIP, a finding that is associated with poor
outcome.
PMID- 11005590
TI - Robotically enhanced "Dresden technique" with bilateral internal mammary artery
grafting.
AB - BACKGROUND: A tendency to reduce the operative trauma seems to be the prominent
sign of development in cardiac surgery. The combination of the previously
introduced minimally invasive "Dresden Technique" with the robotically enhanced
endoscopic system enables further progress in coronary artery surgery. METHODS:
From May 1999, 25 patients (19 male, 6 female, mean age 63 +/- 8.0 years)
suffering from multivessel coronary artery disease (CAD) were treated surgically
using arterial revascularization through the bilateral internal mammary arteries
(BIMA). Both mammaries were harvested endoscopically using the da Vinci robotic
system. Further, the "Dresden Technique" was applied for anastomosis of these
vessels with the coronaries. RESULTS: All patients survived the surgery. Mean
duration of surgery amounted (244 +/- 82.1 min). BIMA dissection took (87 +/-
18.1 min). An average of 2.2 anastomoses were performed per patient.
Postoperatively, the patients remained on ICU for 19 +/- 18 hrs. One patient
needed reexploration for bleeding (4%). CONCLUSIONS: The addition of robotically
enhanced endoscopic mammary artery harvesting method to the "Dresden Technique"
for coronary artery surgery enables the introduction of a new treatment method
for CAD into surgical practice, helping to perform an arterial revascularization
with a distinctly reduced surgical trauma.
PMID- 11005591
TI - Robotic coronary artery surgery--the evolution of a new minimally invasive
approach in coronary artery surgery.
AB - BACKGROUND: With the introduction of a wrist-enhanced robotic surgical system
into minimally invasive cardiac surgery, the outlook of performing closed chest
coronary artery bypass operations became a reality. METHODS: Since May, 1999,
this new wrist-enhanced instrumentation has been used in 109 (79 male, 30 female,
median age 63 +/- 9.9 years) patients. Seven suffering from single vessel
coronary artery disease (SVD) and double vessel disease (DVD) were treated as
totally endoscopic coronary artery bypass (TECAB). 60 with SVD underwent a wrist
enhanced, minimally invasive direct coronary artery bypass procedure. 25 with DVD
were treated using the robotically enhanced Dresden Technique coronary artery
bypass. RESULTS: Survival was 100%. In all patients the IMAs were safely
harvested totally endoscopically. In the TECAB group, all patients were operated
via a three-point stab incision. Data were observed during and after the
operation. CONCLUSIONS: Our preliminary experiences with this new surgical
technique for the robotically enhanced, minimally invasive treatment of coronary
artery disease promote an optimistic way of thinking about the further
development of these procedures.
PMID- 11005592
TI - Clinical use of a computer-enhanced surgical robotic system for endoscopic
coronary artery bypass grafting on the beating heart.
AB - The aim of the study was to perform endoscopic coronary artery bypass grafting on
the beating heart using a surgical robotic system. In the study, the surgical
system ZEUS was used in combination with 3D visualization for endoscopic coronary
artery bypass grafting in 25 patients. In a total of 10 cases, the coronary
artery anastomosis was done on the beating heart using endoscopic stabilizers
without cardiopulmonary bypass. In all cases, total OR time ranged from 4.0 to
8.0 hours (median 5.5 h); the times for endoscopic coronary artery anastomoses
ranged from 14 to 50 minutes (median 25 minutes) with no difference between
arrested-heart or beating-heart procedures. All patients had an uneventful
angiographic control result. An endoscopic coronary artery anastomosis is
possible on the arrested as well as on the beating heart.
PMID- 11005593
TI - Morphological aspects of Ebstein's anomaly in adults.
AB - The essence of the Ebstein's malformation is that the tricuspid valve leaflets do
not attach normally to the valve annulus, and the effective orifice is displaced
downward into the right ventricular cavity at the junction of the inlet and
trabecular components of the right ventricle. Only the septal and posterior
leaflets are displaced and divide the right ventricle into two portions. The
inlet portion is usually integrated functionally with the right atrium
("atrialized portion"), while the other, including the trabecular and outlet
portions, constitutes the functional right ventricle. The proximal atrialized
right ventricle often has a wall thinner than the distal functional right
ventricle, due to partial congenital absence of myocardium. An atrial septal
defect is present in more than one-third of hearts, and the majority of the
remainder has a patent foramen ovale resulting in a right-to-left shunt. The
downward displacement of the septal tricuspid valve leaflet is associated with
discontinuity of the central fibrous body and septal atrioventricular ring, thus
creating a potential substrate for accessory atrioventricular connections and
ventricular pre-excitation making the patient at risk of sudden death.
Angiography has demonstrated that a significant number of patients with Ebstein's
anomaly also have morphofunctional abnormalities of the left ventricle, which may
be explained by increased fibrosis in the left ventricular wall and ventricular
septum as demonstrated by histological studies. Regarding embryology, the
leaflets and tensile apparatus of the tricuspid valve are believed to be formed
mostly by a process of delamination of the inner layers of the inlet zone of the
right ventricle. The downward displacement of the leaflets in Ebstein's anomaly
suggests that delamination from the inlet portion failed to occur.
PMID- 11005594
TI - Ebstein's anomaly in adults: Doppler-echocardiographic evaluation.
AB - A systematic approach and segmental analysis are required for comprehensive
assessment including both morphologic and functional abnormalities associated
with Ebstein's anomaly. The essence of the disease is an apical displacement of
both the septal and the posterior tricuspid leaflets, exceeding 20 mm or 8 mm/m2
in adults. As a consequence, the right heart consists of three components
including the true right atrium, the functional right ventricle (RV) and an
intervening zone that is anatomically ventricular but functionally right atrial
(atrialized RV). The thin wall of the atrialized RV may result in an aneurysm
between the anatomic tricuspid annulus and the apically displaced posterior
leaflet. The annular attachment of the anterior leaflet is normal, which may be
dysplastic and adherent to the RV wall. Tricuspid regurgitation is usually
moderate to severe. Size, shape and function of the functional RV must be
described. The paradoxical motion of the interventricular septum causes
alterations in left ventricular geometry and function. An interatrial
communication is frequently present. Echocardiography is the method of choice to
diagnose Ebstein's anomaly on its own or in association with other heart defects.
PMID- 11005595
TI - Ebstein's anomaly in adults. Arrhythmias: diagnosis and therapeutic approach.
AB - Patients with Ebstein's anomaly (M.E.) are known to have a high potential for
developing arrhythmia, in the vast majority, of the tachycardia type. Most of
these tachycardias are based on accessory pathways (AP) located along the
anomalous atrioventricular valve, found in up to 30% of this patient cohort. Next
to this main representative for congenital arrhythmogenic substrates, various
types of acquired tachycardia were found in patients with M.E., such as atrial
ectopic tachycardia (AET), atrial flutter (A. Flutt.), atrial reentry tachycardia
(ART), atrial fibrillation and ventricular tachyarrhythmia. Refractoriness to
medical treatment and a higher potential for side effects in these patients
resulted in an increasing referral to interventional electrophysiology recent
years. A total of 37 patients with M. E. and tachycardia underwent an attempt for
radiofrequency current (RFC) treatment at our institution, 30 of whom were adults
aged 18 to 61 yrs (33 +/- 12.2. yrs). Just 4 patients under went surgery for
reconstruction of the anomalous valve and closure of an ASD (2 patients), in whom
a total of 6 cases of atrial tachycardia were found, 3 common A. Flutt. and 3
atriotomy-scar related ART. Of the 26 unoperated patients, one presented with
typical AV-nodal reentry tachycardia and the remaining patients with
atrioventricular reentry tachycardia, based on a total of 39 APs. 27/39 Aps had
bidirectional conduction properties, causing the WPW syndrome in 16 patients, 8
APs were concealed and the remaining 4 were Mahaim fibers. Within 39 sessions, 26
of the 30 patients were successfully treated by RFC ablation of the
arrhythmogenic substrates. Mean session duration lasted for 313 +/- 151 min
(range 95 to 660 min), and a fluoroscopy time of 56.0 +/- 38.4 min (2.2 to 146.8
min) was required. There were no severe acute complications. CONCLUSIONS: In
patients with M. E. not only a high potential for the development of tachycardia,
but also a tendency towards multiple arrhythmogenic substrates in the single
patient can be ascertained. RFC ablation can be used safely and effectively for
treatment for various types of tachycardias in patients with M. E.. Such therapy
carries the potential for a definitive treatment and should be taken early into
consideration as it meets the requirements this patient cohort.
PMID- 11005596
TI - Ebstein's malformation. surgical treatment and results.
AB - Ebstein's malformation can be defined as an anomaly of the tricuspid valve
existing in the setting of a right ventricular dysfunction. The technique
introduced by Carpentier in 1980 is based on the concept of mobilization of the
restrictive anterosuperior leaflet associated with a longitudinal plication of
the inlet component of the right ventricle. From January 1980 to December 1999,
142 patients underwent surgery. The mean age was 25 +/- 15 years (1-65). Cyanosis
was present in 48% and associated lesions in 64% of the patients. Patients were
classified using a functional approach according to the severity of the lesions.
Mild displacement of the septal leaflet, along with small size of the atrialized
chamber was seen in 5% (referred to as Type A). Massive displacement of the
septal leaflet, but with normal motion of the anterosuperior leaflet and an
extensive atrialized chamber, was seen in 35% (Type B). In 51%, the mural
(inferior) leaflet was absent, the anterosuperior leaflet was severely restricted
by muscular trabeculations and very short tendinous cords, and the anterolateral
papillary muscle was incorporated in the right ventricular wall. In these
patients (Type C), the atrialized chamber was markedly enlarged and had
dyskinetic walls. In such cases, the contractility of the distal (functional)
right ventricle was also impaired, and some degree of stenosis of the tricuspid
valve was present in one-fifth of them. In the most severe cases (8%), the
leaflet tissue of the valve was extremely reduced and the right ventricular walls
were thin and contracted poorly. This resulted in the so-called tricuspid sack
arrangement (Type D). Valve replacement was needed in only 4 cases, with
conservative surgery being achieved in 138 patients by means of mobilization of
the anterosuperior leaflet and longitudinal plication of the inlet component of
the right ventricle. Additional procedures included the use of a prosthetic ring
(94 patients) and partial Glenn anastomosis (30 patients). The hospital mortality
was 10%, mainly due to acute postoperative right ventricular failure. Actuarial
survival was 75% at 10 years. After operation, 94% of the patients were in
functional class I or II of the New York Heart Association, and 88% had no or
mild tricuspid valve insufficiency as judged by echocardiography. The rate of
reoperation was 9% with a mean delay of 3 years. A second repair was performed in
5 patients. Freedom from reoperation was 87% at 10 years. Sinus rhythm was
present in 81%, and 8 pacemaker devices were implanted, 5 for surgically induced
atrioventricular block, and 3 because of preoperative conduction disturbances.
The use of the partial Glenn anastomosis was introduced recently in cases where
the right ventricular contractility was severely impaired, and/or tricuspid valve
repair was difficult, and/or permanent atrial fibrillation was present. In those
patients with high risk, adding partial Glenn anastomosis reduced the operative
mortality from 24% to 6%. Another benefit of the cavo-bipulmonary anastomosis was
better functional tolerance of mild residual tricuspid valve incompetence. Those
patients with the tricuspid sack arrangement had a high rate of reoperation
(2/11) and valve replacement (3/11), but suffered no operative deaths. We
conclude that tricuspid valvoplasty associated with longitudinal right
ventricular plication is superior to valve replacement. The arrangement producing
a tricuspid sack is not suitable for conservative surgery. An associated cavo
pulmonary anastomosis decreases the operative mortality in patients at high risk,
and seems to preserve right ventricular function.
PMID- 11005597
TI - Complete transposition of the great arteries: surgical concepts for patients with
systemic right ventricular failure following intraatrial repair.
AB - One of the most serious late complications of the intraatrial baffle procedure
(Mustard or Senning correction) in patients suffering from transposition of the
great arteries, (TGA) is the late systemic right ventricular failure. Nearly all
patients presenting with right ventricular dysfunction have severe associated
tricuspid regurgitation. The surgical options for these patients include
tricuspid valve reconstruction or replacement, staged conversion to the arterial
switch operation and orthotopic heart transplantation. Review of 189 operative
survivors who underwent the Mustard or Senning operation for TGA between 1970 and
1993 in our institution revealed 12 patients (6.3%) who died from severe systemic
right ventricular dysfunction (mean follow-up 16+/-3.5 years), which was the most
common cause of late death. All of them had concomitant severe tricuspid
regurgitation. 7 patients (3.7%) died from sudden cardiac death. The actuarial
survival at 10 years is 93% for simple TGA and 85% for TGA associated with
ventricular septum defect or coarctation. At our institution, 4 adolescent or
adult patients underwent tricuspid valve surgery; tricuspid valve replacement was
performed in 2 patients and valve repair in 2 patients. In the mid-term follow
up, 2 of these patients died. Two additional patients underwent orthotopic heart
transplantation, and one died on the waiting list. Staged conversion from the
Senning/Mustard atrial repair to the arterial switch operation was initially
reported by Mee. The procedure for pulmonary artery banding starts with inducing
left ventricular reconditioning with subsequent arterial switch. The mortality of
this two-staged procedure was as high as 20% to 30% in our early experience, and
some of the candidates underwent heart transplantation. Tricuspid valve repair or
replacement do not improve right ventricular function in patients with a failing
right ventricle following the Mustard/Senning operation. Staged conversion to
arterial switch may improve right ventricular function by decreasing the work
load of the right ventricle and provides anatomic repair with left ventricle-to
aorta continuity. Orthotopic heart transplantation is the only alternative if the
left ventricle does not respond to pulmonary artery banding.
PMID- 11005598
TI - 25 years after the first arterial switch procedure: mid-term results.
AB - BACKGROUND: 25 years after the first successful arterial switch operation (ASO)
for complete transposition of the great arteries (TGA), it is possible to
evaluate the mid-term results after this procedure. PATIENTS AND METHODS: From
March 1986 through December 1993, 188 patients with TGA underwent ASO (primary in
181 patients and secondary after previous banding of the pulmonary artery in 7
patients). Of the 181 patients with primary ASO, 152 had simple TGA or TGA with a
small ventricular septal defect, 90 patients had TGA with a large ventricular
septal defect, and 10 had a Taussig-Bing complex. Unselected subgroups of the
patients were specifically examined with respect to general health, cognitive and
motor development, exercise tolerance and cardiological status. Follow-up time
was over 5 years except for the cardiac catheterizations, which were performed
one year after ASO. RESULTS: Early mortality was 6.4% in the total group and 5.5%
in the 181 patients with primary ASO. 5 patients (2.7%) died late and 5 patients
needed reoperation during the follow-up period. Cumulative survival for the whole
group was 91% at 5 and 10 years after ASO. 96% of the patients were unlimited in
their physical activity, and 99% received no medication. Intelligence was not
different from a normal population, but motor and neurological impairment was
more frequent (23% and 9%, respectively). The Bruce treadmill test was normal in
47 of 50 patients, but provoked signs of myocardial ischemia or salvos of
ventricular tachycardia in 3. ECG and Holter ECG showed normal sinus rhythm in
94.5%, important ventricular ectopy in 2.8% and ischemic changes in 1.4%. Right
heart catheterization in 67 patients revealed flattening of the pulmonary trunk
and frequently mild or rarely moderate pulmonary artery branch stenosis. Left
heart catheterization in 71 patients demonstrated significant enlargement of the
aortic annulus and root as well as frequent mild aortic insufficiency. One child
had unexpected coronary artery occlusion,and 2 showed a hypoplastic left anterior
descending coronary artery. In all patients except one, left ventricular ejection
fraction was normal, but 6 patients had regional wall motion abnormalities.
CONCLUSION: These results and those of other groups are encouraging, but
prospective studies over a much longer follow-up time are necessary before
definite conclusions can be drawn.
PMID- 11005599
TI - 40 years after the first atrial switch procedure in patients with transposition
of the great arteries: long-term results in Toronto and Zurich.
AB - The atrial switch procedure dramatically improved the prognosis of children with
complete transposition of the great arteries (TGA). Overall actuarial survival
was approximately 75% after 25 years and was better in patients with simple TGA
than in those with complex TGA. Mortality by any cause (16%) and cardiovascular
mortality (12% and 13%) were comparable in both centers. Progressive congestive
heart failure and sudden death were the principal modes of death. Most of the
survivors denied any symptoms or had mild limitations in their daily activities.
However, long-term problems in this growing population of adults are challenging
and include late arrhythmias (up to two thirds of the patients), systemic
ventricular (SV) failure, systemic atrioventricular valve regurgitation and
reoperations, such as baffle reconstruction, being the most frequent. Objective
assessment of SV function obtained by echocardiography is difficult. It may
include fractional area change and tricuspid annular motion. Survivors after an
atrial switch procedure are unique and have a good quality of life. However, the
definitive and true history of the RV supporting the systemic circulation is not
as yet known.
PMID- 11005600
TI - Primary myxoid sarcoma of the pleura: 5 years follow-up.
AB - Primary sarcomas of the pleura are rare intrathoracic tumours. We describe a case
of a recurring myxoid pleural sarcoma in a 51-year-old male patient with coronary
heart disease, who initially was admitted for coronary revascularization surgery.
Tumour diagnosis was based on pathological examination of a biopsy after
radiological detection of a nodule in the right upper lobe. The nodule was
excised. The first recurrence was diagnosed after 15 months. Pleuropneumonectomy
was done. Four years after the first excision further tumour masses appeared
above the diaphragm and were surgically removed and adjuvant irradiation carried
out. A year later the patient is doing well.
PMID- 11005601
TI - Extended left pneumonectomy combined with off-pump coronary revascularization
(CABG).
AB - Here, we will report on a 63-year-old patient with a centrally located squamous
cell carcinoma of the left lung with complete atelectasis and tumor infiltration
into mediastinal pleura and fat. A known coronary two-vessel disease, which
became highly symptomatic during the operation made a change of the planned
surgical strategy necessary.
PMID- 11005602
TI - Reinforcement of a bronchial stump in VATS lobectomy.
AB - Bronchial stump reinforcement is sometimes required for patients who have a high
risk of developing a bronchial fistula. A lobectomy by video-assisted thoracic
surgery (VATS) is widely used for the treatment of both stage I primary lung
cancer and metastatic central lung cancer, but there has been no report on
reinforcement of a bronchial stump in a VATS lobectomy. We report an aged patient
with stage I primary lung cancer concomitant to diabetes mellitus who was
successfully treated by VATS lobectomy with reinforcement of the bronchial stump
using a pericardial fat pedicle flap. A Harmonic scalpel was very useful and
effective in harvesting the fat pedicle.
PMID- 11005603
TI - Omental flap for mediastinitis after median sternotomy in asplenia syndrome and
gut malrotation.
AB - We describe a 12-year-old patient with asplenia syndrome and gut malrotation who,
after an interim step before a modified Fontan operation, developed life
threatening mediastinitis. A flap of the omentum arising from the transverse
colon, longitudinally located in the left of the abdomen, was created and
transferred to the mediastinum after a division of the arterial arcade at its
most caudal extent. Her postoperative course was uneventful, and 12 months later,
the modified Fontan operation was successfully completed. Although visceral
heterotaxy results in an omental deformation, it does not preclude the use of an
omental flap.
PMID- 11005604
TI - Bilobectomy and amphotericin B in a case of endobronchial mucormycosis.
AB - Lung mucormycosis is a rare fungal infection that has been described mainly in
oncologic and diabetic patients. We here report the case of an endobronchial
lesion caused by this fungus in an immunocompetent person. Prompt diagnosis, and
therapy with Amphotericin B and surgery, permitted the complete resolution.
PMID- 11005605
TI - Optimizing cerebral oxygenation during cardiac surgery: a review of experimental
and clinical investigations with near infrared spectrophotometry.
AB - OBJECTIVES: Near-infrared spectrophotometry (NIRS) is a promising method for non
invasive monitoring of cerebral oxygenation and hemodynamics. This paper reviews
studies in which we aimed to validate NIRS in an experimental model of
cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA)
(validation study), use the method in experimental settings to optimize cerebral
oxygenation during CPB (oxygenation study), and test its utility during routine
cardiac surgery (clinical study). METHODS: Validation study: Forty 8-10 kg
piglets underwent 60 min of DHCA at 15 degrees C, were extubated on the first
postoperative day, and sacrificed on the 4th postoperative day for histologic
investigations. During CPB and DHCA, the animals were investigated by NIRS
(monitoring of cerebral oxygenated hemoglobin (HbO2) and oxidized cytochrome aa3
(Cytox)) and magnetic resonance spectroscopy (MRS) (monitoring of cerebral
adenosine triphosphate (ATP) and phosphocreatine (PCr). Oxygenation study: A
normoxic (n = 5) and a hyperoxic group (n = 5) of piglets underwent 120 min of
DHCA and 6 h of reperfusion with NIRS monitoring. Neuronal damage was evaluated
by histology. Clinical study: Patients (n = 41) undergoing routine cardiac
surgery were investigated by NIRS and neuropsychological testings. RESULTS:
Validation study: Reductions of CytOx and HbO2 values were closely correlated
with decreases in ATP, PCr, and pHi. The changes in CytOx and PCr showed the
strongest correlation (r = 0.623). Maximal CytOx reduction during DHCA predicted
brain damage. Oxygenation study: Histology revealed a significant increase in
brain damage in the normoxic group. Cytox and HbO2 tended to be lower during DHCA
(p = 0.16). Clinical study: During CPB, arterial PCO2, pH and temperature were
closely related to CytOx and HbO2. Patients who suffered from neuropsychological
deficits had a lower CytOx minimum compared to those without these. CONCLUSIONS:
NIRS measurements, especially the CytOx signal, correlate well with high energy
phosphates and have a high sensitivity to predict histologic brain damage. NIRS
is an important and useful tool in studies investigating cerebral oxygenation
during CPB. The CytOx signal predicted impaired neuropsychological outcome in
patients. Therefore, the CytOx signal holds much interest for future studies.
PMID- 11005606
TI - Cardiac surgery in Germany during 1999.
PMID- 11005607
TI - Development of liposome encapsulated clindamycin for treatment of acne vulgaris.
AB - The enhancement of topical delivery of hydrophilic substances by use of
multilammelar liposomes was measured ex vivo on pig ear skin and in vivo on
hairless mice by electron paramagnetic resonance method (EPR). Multilamellar
liposomes with different lipid composition (final concentration of membrane
components is 48 mg/ml) were loaded with a hydrophilic spin probe GluSL, which
does not penetrate the liposome membrane easily. They were characterized with
respect to their stability, entrapped volume and enhancement characteristics. We
observed significant differences in the properties of different types of
liposomes with respect to their stability when in contact with the skin and their
penetration into the skin. The results measured in vivo are consistent with those
obtained ex vivo. On the basis of these findings the liposomes with appropriate
stability and intradermal penetration characteristics were chosen for the
development of liposome-encapsulated 1% clindamycin preparation for therapy of
acne vulgaris. A double-blind clinical study was conducted to assess the safety
and efficiency of liposome-encapsulated 1% clindamycin solution versus 1%
clindamycin solution (Klimicin T, Lek). On the basis of the clinical trial it may
be concluded that liposome-encapsulated 1% clindamycin solution was
therapeutically superior over conventional 1% clindamycin solution in the
treatment of acne vulgaris.
PMID- 11005608
TI - Vitamin C induced apoptosis in human articular chondrocytes.
AB - Chondrocytes present in articular cartilage survive as a resident cell population
throughout the lifespan of the individual organism. However, articular
chondrocytes as other cells also undergo apoptosis and there is an ever
increasing list of diverse stimuli that can induce this phenomenon in vitro. Our
main interest was to investigate potential cytotoxic effects of vitamin C (L
ascorbic acid) on human articular chondrocytes. The present study suggests that
vitamin C can induce apoptosis in a cell culture of chondrocytes after 18 h of
cultivation. Apoptosis-inducing activity of L-ascorbic acid is dose dependent and
significantly affected by the presence of serum. The increased number of vitamin
C induced apoptotic cells was associated with DNA fragmentation and morphological
changes of the cells.
PMID- 11005609
TI - In vitro functional tests for evaluation of stimulating capacity of cultured
human dendritic cells.
AB - Basic functional test for evaluation of in vitro cultured human dendritic cells
(DC) is primary allogeneic one-way mixed lymphocyte reaction (MLR). In this way,
one can evaluate stimulating capacity, which is a basic characteristic of DC. The
proliferation of cells is measured through incorporation of 3H-thymidine.
Normally proliferation is measured at days 5-7. We studied kinetics of
proliferative responses initiated with different stimulating cell suspensions to
evaluate differences and possibly reduce time needed to perform this test.
Gradual increase in response from days 1 to 7 and a significant difference from
controls (peripheral blood mononuclear cells) seen from day 4 was noted if
macrophages were used as stimulators. A consistently higher proliferation,
compared to controls, was always found already on day 2 when mature DC were used
as stimulators. The reaction peaked 2 to 3 days earlier and was also more than
two times more intense. This maximal and significantly higher response,
consistently seen already after 48 hours, allows us to confirm the presence of
mature DC in stimulating suspensions much earlier than previously.
PMID- 11005610
TI - Asymmetrical labeling of giant phospholipid vesicles.
AB - The method for labeling of inner membrane leaflet in unilamellar giant POPC
vesicles was developed and characterised. Symmetrically NBD-PC labeled vesicles
were treated by sodium dithionite, which undergoes an irreversible chemical
reaction with NBD-PC molecule making it non-fluorescent. After the addition of
dithionite the fluorescence on single vesicles as well as on vesicle suspension
showed a 50% decrease of its initial value corresponding to marker quenching in
the outer leaflet. Hence, fluorimetry as well as fluorescence microscopy prove
that dithionite quenching is a suitable method to induce an asymmetrical labeling
of the NBD-PC marked giant vesicles.
PMID- 11005611
TI - The Str mouse as a model for incontinentia pigmenti.
AB - Striated mouse has been proposed as a model for incontinentia pigmenti (IP) based
on the similarities in genetic predisposition and syntenic gene localisation in
mouse. IP is considered an ectodermal dysplasia with all four characteristic
structures involved: sweat glands, hair, teeth and nails. Recently mutations have
been found in the Nsdhl, encoding an NAD(P)H steroid dehydrogenase-like protein
in Str and Bpa mice. We analysed the phenotype of the Str mouse to evaluate the
involvement of ectodermally derived tissues. Our results demonstrated that in Str
mouse in addition to abnormal coat texture, sweat glands were severely dystrophic
or missing. Retinal degeneration and skeletal abnormalities were also found. We
conclude that Str mouse is a good model to get new insights in the pathogenesis
of ectodermal dysplasias and X linked male lethality in humans.
PMID- 11005612
TI - Animal model in the study of colorectal carcinogenesis.
AB - Experimental animal models of neoplastic diseases are important in understanding
etiological and pathophysiological processes also in humans. In order to
investigate whether the mechanism of genomic instability is associated with
chemically induced colorectal tumorigenesis in rat we performed the following
study: One hundred and fifty Wistar rats (males 220-280 g and females 140-180 g)
were used in the study. Colorectal tumors were induced by means of 15 s.c.
applications (20 mg/kg) of 1,2-dimethylhydrazine (DMH). On autopsy, all
intestinal lesions were assessed by histological criteria used in human
pathology. Forty five tumors were found in the large intestine--30 of these in
males and 15 in females, i.e. in 27% of all animals. In four animals multiple
primary tumors were found. Histologically 24 tumours were adenocarcinomas, 14
signet-cell carcinoma and 7 adenomas. DNA was extracted from rat neoplastic
lesions and adjoining microscopically normal tissues from the same slide and
amplified by PCR, using 10 different microsatellite markers from chromosomes 1,
3, 5, 7 and 8. PCR amplicon were analyzed for microsatellite instability with non
isotopic method. In 13 adenocarcinomas (29%) microsatellite instability was found
at a minimum of 1 locus. Seven tumors (15.5%) showed microsatellite instability
at multiple loci. The results of our experiment suggest that genomic instability
is an important molecular event in the pathophysiology of DMH induced colorectal
carcinogenesis in rats.
PMID- 11005614
TI - Soluble tumor necrosis factor receptor I (sTNFRI) as a prognostic factor in
melanoma patients in Slovene population.
AB - Tumor necrosis factor alpha (TNF-alpha) and its receptors (TNFRI and TNFRII)
which exist in soluble form as a product of cleavage of the extracellular domain
of membrane integrated receptors, still rise debate about their importance. It
was reported that TNF-alpha has numerous actions in diseases such as
inflammation, autoimmunity, infectious diseases, septic shock and many types of
cancer [1, 2]. Several authors have reported the significance of sTNFRI level in
serum of cancer patients [3, 4]. This study was performed in collaboration with
the Institute of Oncology of Slovenia. At least two different mouse monoclonal
antibodies (MAbs) against human sTNFRI have been prepared to obtain a sensitive
and reliable sandwich ELISA. It was compared with commercially available R&D and
Endogen ELISAs for the determination of sTNFRI. Groups of patients with different
stages of melanoma and epithelial ovarian carcinoma were tested and their
clinical records were reexamined. Levels of sTNFRI were measured and compared
with the normal serum levels of sTNFRI.
PMID- 11005613
TI - Human peripheral blood lymphocytes sensitised to PPD respond to in vitro
stimulation with increased expression of CD69 and CD134 activation antigens and
production of Th-1 type cytokines.
AB - Individuals sensitised to Mycobacterium tuberculosis antigens by infection,
vaccination or Mantoux test generate specific memory cells. The response to in
vitro restimulation with PPD is observed as the lymphoid cell proliferation and
production of Th-1 type cytokines. Cell-mediated immune response was measured by
Mantoux test, lymphocyte blast transformation test, estimation of IFN-gamma
production (Quantiferon, ELISPOT), and expression of CD69 and CD134 molecules on
the T-helper lymphocytes (CD4+). All the methods used were compared for parity of
the results. According to Mantoux test results, the patients could be distributed
into two groups: responder and non-responder group. Induration in Mantoux test
after a new contact with PPD in non-responders was smaller than 5 mm, they
produced only small amounts of IFN-gamma, lymphocyte blast transformation was
poor, and expression of CD69 and CD134 was low. In responders reaction was much
more intensive in all tests measured. We conclude that the reactivity of memory
cells to M. tuberculosis antigens can be effectively detected by Mantoux test.
The same was true also for the in vitro tests presented but in addition the in
vitro tests give more information about the mechanism involved in the immune
response against M. tuberculosis.
PMID- 11005615
TI - Modulation of tumour necrosis factor production with desmuramyldipeptide
analogues.
AB - Some synthetic analogues of the immunomodulatory agent muramyl dipeptide (MDP),
i.e. phthalimido- (LK-511, LK-413, LK-512, LK-423, LK-508), adamantyl- (LK-415,
LK-517), 7-oxoalkyl-(LK-409) desmuramylpeptides were assessed for the tumour
necrosis factor (TNF) inducing activity and the ability to modulate TNF
production in in vitro phorbol 12-myristate 13-acetate (PMA) & ionomycin
stimulated cultures of human peripheral blood mononuclear cells. A kinetic study
over a 40-hour period indicated that desmuramyldipeptides were weak TNF inducers
compared to romurtide, PMA & ionomycin or lipopolysaccharide. By contrast, they
showed the potential to up- or down-regulate the production of TNF evoked by PMA
& ionomycin, which was strongly dependent on the time of the stimulation. After
4h of stimulation, the TNF secretion was augmented by LK-508, LK-409 and LK-511,
after 18 h by LK-409 and LK-423, and after 40 h by LK-423, LK-511, LK-415 and LK
512. However, LK-517 and LK-512 inhibited the secretion of TNF after the 18-h
period.
PMID- 11005616
TI - Immune response in lymphocyte cultures stimulated by oral bacteria preparations.
AB - Lymphocyte cultures were used as an in vitro experimental model to get a deeper
insight into immune response to oral bacteria in periapical granulomas.
Lymphocytes isolated from leucocyte concentrate were in lymphocyte cultures
stimulated by antigen preparations of oral bacteria. Lymphocyte subsets that have
developed in lymphocyte cultures after a week of stimulation were analysed by
flow cytometry. A significant increase in expression of INF-gamma molecules in
CD3+ cells stimulated by antigen preparations of oral streptococci was found,
compared with negative control. On the other hand we observed a significant
increase in expression of IL-4 in CD3+ cells stimulated by antigens of anaerobic
bacteria, compared with negative control. Our results show that antigens of oral
streptococci in in vitro lymphocyte cultures induce the differentiation of T
helper cells into Th2 cells and that antigen preparations of anaerobic bacteria
induce the differentiation of T helper cells into Th1 cells. Furthermore, an
increased expression of HLA-DR molecules on CD8+ T cells stimulated by antigens
of oral streptococci was found, compared with negative control.
PMID- 11005617
TI - Shift from Th2 to Th1 response in immunotherapy with venoms.
AB - Cytokines released from T lymphocytes regulate antibody production by B
lymphocytes and releasability of mast cells and basophils. Immune tolerance in
specific allergen (Ag) immunotherapy (SIT) might be a consequence of decreased
Th2 or increased Th1 response of Ag specific T lymphocytes. We compared function
of T lymphocytes in 11 patients with Hymenoptera venom allergy and in 7 healthy
volunteers. We followed function of T lymphocytes in 6 patients during SIT. We
measured released IL-2, IFN-gamma, IL-4 and IL-5 from Ag and mitogens (either
with phorbol-myristate-acetate (PMA) and ionomycin or anti-CD3 antibodies)
stimulated peripheral blood mononuclear cells (PBMC). After stimulation with Ag
PBMC of patients released 86 +/- 133 pg/ml IFN-gamma and 19.7 +/- 20.1 pg/ml IL-4
(Th2 response), PBMCs of healthy controls released 184 +/- 116 pg/ml IFN-gamma
and 4.8 +/- 8 pg/ml IL-4 (Th1 response). Spontaneous release of IFN-gamma in
cultures of PBMC of patients increased after rush SIT (before: 25 +/- 31 pg/ml,
after 241 +/- 281 pg/ml, p<0.05). After 6 months of SIT response of PBMCs of
patients became similar to response of PBMCs of healthy controls. Time pattern of
cytokines secreted from PBMCs after stimulation with PMA and ionomycin was
different than after stimulation through T-cell receptor/CD3 complex.
PMID- 11005618
TI - Interleukin-8 and procalcitonin in early diagnosis of early severe bacterial
infection in critically ill neonates.
AB - We studied the value of serum interleukin-8 (IL-8) and procalcitonin (PCT) in the
early diagnosis of early severe bacterial infection in 58 critically ill
ventilated neonates. ELISA was used for determining IL-8 and immunoluminometric
assay for PCT. IL-8 and PCT were compared with routinely used serum C-reactive
protein (CRP). Neonates were divided into four groups: Ia--proven severe
bacterial infection (n = 9), Ib--clinical sepsis (n = 16), II--respiratory
distress without bacterial infection (n = 12), and III--various types of neonatal
distress (n = 21). Sera were collected on admission, at 24 h and 48 h after
admission. There was no significant difference between groups Ia and Ib for
either parameter at any time interval. Significant difference was found between
group Ia+b (septic neonates) and group II for PCT and CRP at 24 and 48 h, but not
for IL-8. There was no difference between group Ia+b and group III except for CRP
at 24 h. Diagnostic accuracy was best for PCT on admission and for CRP at 24 h.
Serum PCT and IL-8 are not specific markers for early severe bacterial infection
in critically ill neonates and are not better than CRP.
PMID- 11005619
TI - Interleukin-6 (IL-6) and soluble receptors for interleukin-2 (sIL-2R) in the
diagnosis of early severe infection in the critically ill newborns.
AB - The aim of our study was to evaluate the diagnostic accuracy of serial
determination of interleukin-6 (IL-6) and soluble receptors of interleukin-2 (sIL
2R) in the diagnosis of early infection in the critically ill newborns and
compare it with the routinely used C-reactive protein (CRP). Fourty-six
critically ill newborns (median age 8 h, range 1-96 h), treated at the
multidisciplinary intensive care unit, Division for Paediatric Surgery and
Intensive Care, University Medical Centre Ljubljana, were included in the study.
Newborns were divided into three groups: group I microbiologically confirmed
severe infection (n = 14), group II suspected but not confirmed infection (n =
12) and group III respiratory distress syndrome without laboratory signs of
infection. Serum concentrations of IL-6, sIL-2R and CRP were determined on
admission and at 12 and 24 h after admission. On admission the concentrations of
IL-6 and sIL-2R were significantly higher in group I than in group III, but there
was no difference between groups I and II. On admission area under receiver
operating characteristic (ROC) curve for IL-6 was 0.756, for IL-2R 0.821 and for
CRP 0.799. Repeated determination at 12 h improved diagnostic accuracy for sIL-R
and CRP but not for IL-6.
PMID- 11005620
TI - Murine monoclonal antibodies directed against human recombinant Macrophage
Migration Inhibitory Factor.
AB - Macrophage Migration Inhibitory Factor (MIF) is a crucial component of the immune
system acting together with glucocorticosteroids to regulate immunity and
inflammation. Understanding of its many putative functions and action mechanisms
is still ambiguous. Due to the newest findings that a local MIF expression is up
regulated in allograft rejection and in glomerulonephritis, an interest in MIF
research is increasing and is focused on possibilities of anti-MIF treatment. In
the present work new murine monoclonal antibodies (MAbs) directed against human
recombinant MIF (hrMIF) are described. hrMIF protein used for the immunisation
was tested for its biological activity and has evident macrophage migration
inhibitory activity. The selected MAbs were purified and further characterised.
They recognised MIF in a Western blot experiment after a native IEF. Anti-MIF MAb
designated as M1 inhibited MIF activity in the test, which was performed in the
48 well Boyden chamber system. It is presumed that M1 MAb could be used as a
potential therapeutic agent.
PMID- 11005621
TI - Effects of molgramostim, filgrastim and lenograstim in the treatment of
myelokathexis.
AB - Myelokathexis is a very rare form of chronic hereditary neutropenia resulting
from impaired neutrophil releasing mechanism in the bone marrow. The recombinant
human granulocyte-macrophage (molgramostim) and granulocyte (filgrastim,
lenograstim) colony stimulating factors release the mature granulocytes from the
bone marrow. We describe a 43-year-old woman suffering from myelokathexis, with
the absolute neutrophil count ranging between 0.03 and 1.35 x 10(9)/L. In the
period before the introduction of cytokines, the patient had more than 80 major
infectious episodes. Since 1991, infections in this patient have been treated
with cytokines, given in conjunction with antibiotics. Initially, she received
molgramostim in a daily dose of 5 microg/kg subcutaneously, which stimulated the
release of granulocytes from her bone marrow, thereby allowing successful
treatment of infection. After the development of hypersensitivity, molgramostim
was substituted with filgrastim. Finally, lenograstim was given a trial. With all
three cytokines, the patient's neutrophil count always attained normal values
already 4 hours after subcutaneous application of the drug in a dose of 5
microg/kg, the highest neutrophil levels were measured at 24 hours post
injection, and the neutrophil count was again close to the baseline value 72
hours after the treatment. A slight neutropenia was present 48 hours after the
application of filgrastim. We believe that all three cytokines are equally
effective in increasing the neutrophil count in venous blood of patients with
myelokathexis.
PMID- 11005622
TI - Expression of human lymphotoxin alpha in Aspergillus niger.
AB - A gene-fusion expression strategy was applied for heterologous expression of
human lymphotoxin alpha (LTalpha) in the Aspergillus niger AB1.13 protease
deficient strain. The LTalpha gene was fused with the A. niger glucoamylase GII
form as a carrier-gene, behind its transcription control and secretion signals.
Special attention was paid to the influence of different codon usage on secretion
of protein. In the case of human tumor necrosis factor alpha (TNFalpha) a
dramatic change of secretion has been observed when human cDNA sequence was used
instead of synthetic E. coli biased codons. In the case of LTalpha such a change
of codon usage brought improvement at the RNA level, however, no increase in the
quantity of secreted protein was observed, due to the proteolitic activity of the
host organism. The estimated yield of secretion of LTalpha from A. niger into the
soya medium was 50 pg l(-1) of culture.
PMID- 11005623
TI - Immune response in chronic periapical parodonititis.
AB - The purpose of our study was to investigate the immune response in chronical
periapical parodontitis (CPP) by using multidisciplinary approach. 30 CPP samples
were obtained after surgical removal--apicoectomy. Each CPP sample was examined
by histological, bacteriological and flow cytometrical (FC) analysis of
lymphocytes infiltrating CPP samples. Ten percent of bacteriological samples were
sterile, others had significant aerobic and anaerobic growth. We used
pathohistologic and microbiologic findings and compared them to the results of
immunological analysis. By FC we found a significant increase in proportions of T
lymphocytes expressing interleukin-2 receptors and ICAM-1 compared to peripheral
blood lymphocytes. Proportions of T helper cells that produce interferon-gama
(IFN-gamma) was higher in CPP samples predominantly colonized by anaerobic
bacteria. There were no differences in IL-4 expression by T cells in both groups
(anaerobic and streptococcal). Among anaerobic CPP samples differences in
proportion of T cells that express IL-2 receptors expression was also found
between samples colonised by P. acnes and Bacteroides sp. Oral streptococci cause
relatively limited tissue destruction and induce Th2 type of immune response
accompanied by non-cytotoxic inflammatory reaction. On the contrary, anaerobic
bacteria induce Th1 type of immune response that cause more severe inflammatory
reaction (type 4) of hypersensitivity that damage the tissue by the action of
cytotoxic T cell activation.
PMID- 11005624
TI - Diminished Th1-type cytokine production in gastric mucosa T-lymphocytes after H.
pylori eradication in duodenal ulcer patients.
AB - Helicobacter pylori infects an estimated 50% of the world population, however
only a small proportion of individuals develop clinical symptoms of gastritis,
peptic ulceration or gastric cancer. The variations in disease presentation may
be due to differences in bacterial virulence and/or immune response to the
pathogen. In the previous study we reported an increased expression of the IL-2
receptor in duodenal ulcer (DU) patients infected with H. pylori. This study
examined intracellular lymphokine production in gastric mucosa infiltrating T
lymphocytes in DU patients before and after H. pylori eradication. T lymphocytes
were isolated from gastric mucosa biopsies by using mechanical and enzymatic
tissue desegregation. Ficoll-purified lymphocytes were incubated with monoclonal
antibodies and analysed by using 3-colour flow cytometry analysis for
intracellular interferon gamma (IFNgamma) and interleukin 4 (IL-4) expression in
order to define Th1 and Th2 cell population. We demonstrated a significant
decrease in the proportion of Th1 cells infiltrating gastric mucosa 6 and 12
months after H. pylori eradication. Our results suggest the importance of the
local immune response in the development of H. pylori related gastritis.
PMID- 11005625
TI - A mouse model of chronic bacterial lesions (a cotton trap) for studying oral
bacteria-lymphocyte interactions.
AB - We established a mouse model of chronic bacterial infection (cotton trap) to get
a deeper insight into interactions between immune cells and bacterial strains,
that are most commonly isolated from periapical processes. We have used flow
cytometry to identify the presence of intracellular cytokines of activated T
cells collected from cotton traps, previously infected with different strains of
bacteria and implanted subcutaneously into the back of the mice. We provide an
evidence that anaerobic bacteria (Bacteroides sp.) and nocardiae are more
effective in inducing cytotoxic immunity and Th1 response compared to oral
streptococci. Differences in immune response against anaerobic bacteria when
compared to streptococci are probably dependent on some non-specific immune cell
stimulation (e.g. by bacterial cell wall components), nevertheless the role of
specific antigen-dependent immune mechanism can not be excluded.
PMID- 11005626
TI - Changes in Th1/Th2 cytokine balance in Graves' disease.
AB - Graves' disease (GD) is characterised by hyperthyroidism, caused by stimulatory
thyrotropin receptor (TSHR) antibodies. Recent research shows that an important
factor in the pathogenesis of autoimmune diseases is the change in the balance
between Th1 cytokines, which promote cell mediated immunity, and Th2 cytokines,
which promote humoral immunity. There are contradictory data about this balance
shift in GD. Our objective was to determine the Th1/Th2 cytokine balance shift in
patients with newly diagnosed GD, when compared to the same balance in healthy
controls. We isolated mononuclear cells (MNC) from the peripheral blood of
healthy donors and from patients with newly diagnosed GD before treatment. The
MNC were activated with ionomycin in combination with phorbol 12-myristate 13
acetate (PMA). After 40-hour incubation, the concentrations of the cytokines
produced (IFN-gamma, IL-4, IL-10, IL-12) in the culture supernatants were
measured by ELISA (Endogen, USA). The MNC cultures from patients with GD produced
significantly less IL-12 and significantly more IL-10 and IL-4 than MNC cultures
from healthy controls. All calculated ratios of Th1 against Th2 cytokines in MNC
cultures from patients with GD were significantly lower than in MNC cultures from
healthy controls. Our results show a systemic shift of cytokine production in
patients with GD toward the Th2 cytokine response, thus confirming the key role
of TSHR antibodies and humoral immunity in the pathogenesis of GD.
PMID- 11005627
TI - Cytokine-regulated secretion of nerve growth factor from cultured rat neonatal
astrocytes.
AB - Interactions involved in the regulation of nerve growth factor (NGF) release by
inflammatory cytokines: interleukin-1beta (IL-1beta), interleukin-6 (IL-6),
tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1
(TGF-beta1) were examined in rat neonatal cortical astrocytes in primary culture.
Exposure of cultured astrocytes to IL-1beta, IL-6, and TGF-beta1 resulted in the
stimulation of NGF secretion. Treatment of cells for 24 h with IL-1beta (10
U/ml), IL-6 (5 ng/ml) and TGF-beta1 (5 ng/ml) caused 3-, 1.8-, and 2.8-fold
increase in NGF secretion as compared to the control cells. In contrast, TNF
alpha (30 ng/ml) by itself had no stimulatory action on NGF release whereas co
stimulation of astrocytes with IL-1beta and TNF-alpha showed a synergistic
interaction. Co-treatment of astrocytes with IL-1beta and TGF-beta1 increased NGF
secretion in an additive way, whereas simultaneous application of IL-1beta and IL
6 resulted in the inhibitory effect on NGF secretion. Our results suggest that
interactions between cytokines used cause the stimulation of NGF secretion
through different regulatory mechanisms.
PMID- 11005628
TI - The effects of histamine and interleukin-6 on NGF release from cortical
astrocytes in primary culture.
AB - The influence of neurotransmitter histamine and cytokine interleukin-6 (IL-6) on
nerve growth factor (NGF) release was studied in rat neonatal cortical astrocytes
in primary culture. Exposure of astrocytes to either histamine or IL-6 resulted
in the stimulation of NGF release. Maximal stimulation of NGF release was
obtained using histamine at concentration 100 nM after 24 h of treatment (2.3
fold increase over the basal secretion from the control cells). IL-6 (30 ng/ml)
induced NGF secretion was 1.66 fold over the basal level. Time course of NGF
release, after histamine or IL-6 treatment, showed elevation of NGF level in the
culture medium after 8 h or 24 h, respectively. IL-6 antibody effectively blocked
the IL-6 stimulatory effect on NGF release, but did not influence NGF release,
evoked by histamine. IL-6 antibody alone did not show any influence on NGF
release. Our results suggest that IL-6 and histamine stimulate release of NGF by
two different and independent molecular pathways.
PMID- 11005629
TI - Effects of ammodytin L on miniature and endplate potentials in neuromuscular
junction of frog m. cutaneus pectoris.
AB - Neurotoxic effects of ammodytin L (AtnL), a potent phospholipase A2 homologue,
was studied in frog neuromuscular preparation m. cutaneous pectoris by measuring
the influence of the toxin on the amplitude and the frequency of miniature and
endplate potentials (MEPPs, EPPs). AtnL, in 100 nM concentration, significantly
increases spontaneous quantal acetylcholine release from the motor nerve endings,
observed as the increase in MEPPs frequency. At 100 nM or higher concentration
the toxin decreases EPPs amplitude and the membrane potential (MP)
simultaneously. No significant effect of AtnL on EPPs was observed at any
concentration bellow 100 nM. Our results indicate that in frog AtnL shows the
typical myotoxic effects, but it also exerts presynaptic effects.
PMID- 11005630
TI - Subchronic liver injuries caused by microcystins.
AB - The subchronic effects of cyanobacterial lyophilizate (CL) containing
microcystins on liver were investigated in female New Zealand rabbits. Sterilised
CL containing microcystins was injected i.p. Liver toxicity was assessed by
histological examination of liver samples. Non-invasive magnetic resonance
imaging (MRI) of liver was also performed in order to assess changes in the
homogeneity of liver tissue. Subchronical intoxication with microcystins caused
morphological changes of liver tissue that were also detected by use of MRI.
Histological analysis showed that changes seen on MRI represent liver injury
characterised with fatty infiltration and periportal fibrosis. This demonstrates
that subchronic exposure to microcystins can lead to liver degeneration, which
can easily be detected in vivo by use of MRI.
PMID- 11005631
TI - The influence of quantal content on the time course of the endplate current in
frogs.
AB - The aim of this study was to find out whether control and facilitated endplate
current (EPC) of a curarized frog nerve-muscle preparation stimulated with paired
impulses decay at the same time constant. The experiments revealed that the decay
of the greater second EPC was slower in nearly half of the cases. This half of
the results suggests that a larger quantity of the released transmitter and,
consequently, a higher density of open channels promote a cooperative effect
among them. The end effect can be a longer mean lifetime of open acetylcholine
channels. In the other half of the experiments, the mean lifetime of open
channels seems to be independent of the agonist concentration.
PMID- 11005632
TI - Sensitivity of peripheral nerve fibres to sodium pentobarbital anaesthesia in
rat.
AB - The sensitivity of different classes of peripheral nerve fibres to anaesthesia
with sodium pentobarbital in rat was tested. The basic approach was to examine
changes in compound action potential (CAP) in a rat sural nerve induced by sodium
pentobarbital. Rats were either sacrificed by cervical dislocation (control) or
anaesthetized with sodium pentobarbital (100 mg/kg, i.p.), and a 30 mm long sural
nerve segment excised and placed on electrodes in a thermostatically controlled
recording chamber. CAPs were evoked by electrically stimulating the sural nerve
segment with supra-threshold stimuli. CAP in control sural nerves consisted of
the early component (A axons: 32.73 +/- 2.91 m/s) and the late component (C
axons: 0.92 +/- 0.05 m/s) with peak voltage amplitudes 4.9 +/- 1.0 mV and 0.1 +/-
0.03 mV, respectively. Anaesthesia with sodium pentobarbital had no effect on CAP
latency. However, the amplitude of CAP of both A and C axons was reduced by
approximately 40% and 50%, respectively. The depressant effect of pentobarbital
on CAPs was statistically significant for both groups of axons (p<0.01). Non
selective sensitivity of A and C axons to pentobarbital suggests even
distribution of receptors for GABA in these two populations of axons in the rat
peripheral nerve.
PMID- 11005633
TI - Phosphate metabolism in red blood cells of critically ill neonates.
AB - Very few data exist on phosphate metabolism in critically ill neonates. Therefore
we studied the incidence of hypophosphataemia, the intracellular metabolism of
phosphate by measuring adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate
(2,3-DPG) in red blood cells, and excretion of phosphate in urine. The aims of
the study were early detection of changes in phosphate metabolism as possible
diagnostic markers of sepsis and defining the cause of hypophosphataemia.
Neonates, treated in multidisciplinary paediatric intensive care unit (PICU),
included in the study, were less than three days of age. Eighteen of them had
respiratory distress syndrome (RDS) and 16 had microbiologically confirmed or
clinical sepsis. The overall incidence of hypophosphataemia in critically ill
neonates was over 80%, and was more common (88%) and more profound in those with
sepsis than in those with RDS (79%). Therefore the septic neonates needed
significantly larger amounts of phosphate to maintain normophosphataemia. In
septic neonates ATP concentration in red blood cells was significantly lower than
in neonates with RDS and controls, while the 2,3-DPG concentration was increased
as a result of compensation. In septic neonates urinary losses of inorganic
phosphate (Pi) were significantly higher than in neonates with RDS.
Hypophosphataemia in critically ill neonates is at least partly due to higher
urinary losses of phosphate.
PMID- 11005634
TI - Effect of mechanical load on acetylcholinesterase mRNA levels in the slow soleus
muscle of the rat.
AB - The influence of mechanical load on the levels of acetylcholinesterase (AChE)
mRNA was studied in order to examine to which extent different loading conditions
may be responsible for differences in AChE regulation between the soleus, which
is an antigravity muscle, and the fast EDL muscle. Forty-eight female rats were
randomly assigned to three groups: a group with hindlimb suspension producing
soleus muscle unloading, a group with ablation of synergistic gastrocnemius
muscle causing overload of the soleus muscle, and the control group. The soleus
muscles were isolated after 8 days of treatment AChE mRNA levels were analyzed by
Northern blots and evaluated densitometrically. The values were normalized with
beta-actin mRNA level, and then a value of 100% was assigned to the mRNA level in
the control EDL muscle. Muscle unloading did not produce a significant increase
of the AChE transcript levels, but the levels were rather variable. However, a
statistically significant increase of AChE mRNA levels was observed in overloaded
soleus muscles. These results corroborate the hypothesis that the slow and fast
patterns of activity appear more important then muscle loading for the
differences in regulation of AChE mRNA levels in fast and slow muscles.
PMID- 11005635
TI - Subunit interface selective toxins as probes of nicotinic acetylcholine receptor
structure.
AB - The pentametric assembly of the nicotinic acetylcholine receptor with two of the
five subunit interfaces serving as a ligand binding sites offers an opportunity
to distinguish features on the surfaces of the subunits, and their ligand
specificity characteristics. The receptor from mammalian muscle, with its
circular order of homologous subunits (alphagamma alphadelta beta), assembles in
a unique arrangement. The residues governing assembly can be ascertained through
mutagenesis. Selectivity of certain natural toxins is sufficient to distinguish
between sites at the alphagamma and alphadelta subunit interfaces. By
interchanging residues on the gamma and delta subunits through mutagenesis, and
ascertaining how they interact with the alpha subunit, determinants forming the
binding sites can be delineated. The alpha-conotoxins show a 10,000-fold
preference for the alphadelta over alphagamma subunit interface with alphaepsilon
falling in between. The waglerins show a 2,000-fold preference for alphaepsilon
over the alphagamma and alphadelta interfaces. Finally, the alpha-neurotoxin from
N. mossambica mossambica shows a 10,000-fold preference for the alphagamma and
alphadelta interfaces over alphaepsilon. Identification of interactive residues
through mutagenesis, when coupled with homology modeling of domains and site
directed residue modification, has revealed important elements of receptor
structure.
PMID- 11005636
TI - Cholinesterase: substrate inhibition and substrate activation.
AB - The relationship between activities and substrate concentrations (pS-curves) was
analysed for reactions of acetylcholinesterase (EC 3.1.1.7) and
butyrylcholinesterase (EC 3.1.1.8). Catalytic constants Km, Kss, Vm, n and b were
calculated from the Michaelis, Haldane, Hill and Webb equations in order to
assess whether a given substrate also acts as an inhibitor or activator. It is
suggested that the term substrate inhibition should only be attributed to
substrates revealing bell-shaped pS-curves, while the terms apparent substrate
inhibition or apparent substrate activation should relate to calculated values of
the catalytic constants.
PMID- 11005637
TI - Role of alpha-adrenoceptors in the cutaneous postocclusive reactive hyperaemia.
AB - Laser-Doppler (LD) flow measurements reveal typical flow oscillations in the
descending part of the cutaneous postocclusive reactive hyperaemia (PRH). The
origin of these oscillations is still poorly understood. We tested the hypothesis
that the high frequency (HF) components within the frequency band 0.06-0.2 Hz are
due to the local myogenic mechanism, whereas the low frequency (LF) components
within frequency band 0.01-0.05 Hz reflect sympathetic vasomotor activity. LD
flow was monitored on fingertips of 11 healthy volunteers before and after an 8
minute occlusion of digital arteries. We studied the effect of intradermal
microinjection (1 microl) of alpha-antagonists (prazosine, yohimbine) and alpha
agonists (phenilephrine, clonidine) on PRH oscillations. We analysed the
magnitude of peak flow and its duration and performed spectral power analysis to
obtain fundamental HF and LF frequencies (defined as components with the highest
amplitude in the part of the respective frequency band). The results (mean +/-
SE) for each substance were compared to the control values obtained after
microinjection (1 microl) of 0.9% NaCl. The fundamental HF significantly
decreased from 0.11 +/- 0.008 Hz after an injection of saline solution to 0.08 +/
0.006 Hz after an application of antagonists (p<0.05). The local application of
alpha-antagonists did not abolished HF oscillations what suggests that activity
of local sympathetic nervous system is not essential in generation of these
oscillations. However, the significant decrease of fundamental frequency in HF
band after application of alpha-antagonists supports the hypothesis of their
local origin and could be explained by the effect on pacemaker myogenic
mechanism.
PMID- 11005638
TI - Spatial resolution of epicardial pace mapping using body surface potentials.
AB - Body surface potential maps (BSPMs) recorded during pace mapping provide an
important non-invasive means for identifying local cardiac events; recent
clinical studies demonstrated that endocardial pacing sites can be resolved
within less than 10 mm. We sought to determine whether similar spatial resolution
could be achieved during epicardial pacing. Four patients who were undergoing
either heart valve replacement (one), aortocoronary bypass graft (one), or both
(two) were studied. In each patient, a pair of epicardial electrodes was placed
intraoperatively at the middle aspect of the right ventricular free wall. The
distance between the neighbouring electrodes was 10 mm. Five days after the
surgery, ECGs were acquired from 35 leads during pacing from each epicardial
electrode. We determined the distributions of QRS integrals (the net area under
the ECG signal) and compared integrals corresponding to pacing from each of the
adjacent electrodes using statistical indices. Student's t-test was applied to
these indices and in all the patients revealed that differences in distributions
of QRS integral maps were statistically significant (p < 0.01). Results of our
study indicate that the non-invasive acquisition of body surface ECGs could
resolve epicardial breakthrough sites within 10 mm, which may be useful in
facilitating therapeutic ablations in patients with ventricular tachycardias.
PMID- 11005639
TI - Improvement of early functional atherosclerotic changes in males with
hypercholesterolemia after vitamin E supplementation.
AB - Vitamin E as an antioxidant vitamin reduces the susceptibility of low-density
lipoprotein (LDL) cholesterol to oxidation and may have antiatherosclerotic
effects. We tested the hypothesis that six months of 400 mg vitamin E
supplementation favourably affects early functional changes in atherosclerotic
process in subjects with hypercholesterolemia. The diameter of the brachial
artery at rest, after reactive hyperemia (representing endothelium-dependent
vasodilatation) and after sublingual glyceryl-trinitrate (representing
endothelium-independent vasodilatation), were determined by ultrasonographic
method (B mode) before and after the intervention period. After the intervention
period the brachial endothelium-dependent vasodilatation increased significantly
in the vitamin E group while it did not change in the placebo group. In
conclusion, six months of oral vitamin E supplementation results in improvement
of the endothelium-dependent vasodilatation in men with hypercholesterolemia.
PMID- 11005640
TI - Protein-polyphenol interactions and in vivo digestibility of buckwheat groat
proteins.
AB - A rat model system, based on a diet with (Nb+) or without (Nb-) the inclusion of
0.7% of a 2:1 (w/w) mixture of Bacitracin and Neomycin sulfate (Nebacitin) was
used to elucidate interactions of polyphenols with proteins in buckwheat. The
treatment with the antibiotic Nebacitin suppresses the microflora in the large
intestine and is used to obtain an estimate of the digestion occurring in the
small intestine. Experimental buckwheat samples were obtained in order to contain
different levels of polyphenol and were subjected to different hydrothermal
treatments. It was found that a considerable interaction between polyphenols and
proteins appeared during the hydrothermal treatment, and this interaction reduces
the digestion of proteins through the small and large intestine. Microbial
processes in the colon enhance the digestibility of protein, blocked by
polyphenols in hydrothermally processed buckwheat.
PMID- 11005641
TI - Measurement of porcine heart temperatures.
AB - During cardiac surgery local hypothermia of the heart is used to slow down
cellular metabolism. It has been shown by computer simulation that heart muscle
is not uniformly cooled to the desired temperatures. The aim of our work was to
find out a way for measuring the temperatures of the ventricular wall and the
septum with +/-0.1 degrees C accuracy. The measurement protocol should be
applicable during operations on the human heart, during which disturbing factors
should be minimized. We have tested the protocol and the equipment on porcine
hearts. Two types of probes were tested, the contact-probe, which can be attached
to the heart-wall surface, and the needle-probe, which can be inserted into the
heart tissue. Before experiments the probes were calibrated and their heat
transfer characteristics determined. We conclude that the probes and the protocol
are suitable for studying the effects of cardioplegia, and for checking the
results previously obtained by computer simulation.
PMID- 11005642
TI - Biochemical and biophysical conditions for blood clot lysis.
AB - We have studied how pharmacological dissolution of blood clots was affected by
clot retraction, the mode of transport of fibrinolytic agents into the clot and
the thickness of the composite fibrin fibers. Retracted clots were resistant to
fibrinolysis in a milieu without dissolved plasminogen, because the amount of
fibrin-bound plasminogen in retracted clots was insufficient for successful clot
lysis. In plasma containing plasminogen, retracted clots were successfully lysed
with fibrin-specific plasminogen activators, but not with non-fibrin-specific
activators. Preincubation of retracted clots in plasma increased their
plasminogen content as well as their sensitivity to fibrinolysis. The rate of
lysis was increased up to 100-times when plasminogen activator and plasminogen
were introduced into cylindrical clots by pressure-induced bulk flow in
comparison with diffusion alone. The magnitude of the increase was similar in
retracted and nonretracted clots, but the absolute rate of lysis was faster in
non-retracted clots. The influence of fibrin fiber thickness on fibrinolysis was
studied by atomic force microscopy. The time to complete lateral section of
fibers did not differ between thick and thin composite fibers, and the rate of
diameter reduction was faster in thick fibers than in thin ones. Taken together
our results suggest that lysis of retracted clots proceeds in circular stages:
(a) activation of bound plasminogen followed by partial degradation of fibrin,
(b) opening of new plasminogen-binding sites on partly degraded fibrin, (c)
binding of plasminogen to the new binding sites which enhances the susceptibility
of clots to lysis. Lysis is accelerated by bulk flow of plasminogen activator and
plasminogen into clots in comparison to diffusion alone. Fibrinolysis of thick
composite fibrin fibers proceeds more efficiently than lysis of thin fibers.
PMID- 11005643
TI - Possibilities for clinical use of prostacyclin in vascular disease.
AB - Currently available drug therapies for patients suffering severe ischaemia with
rest pain and trophic lesions of the limbs remain unsatisfactory. Also vascular
reopening procedures are suitable in only about half of the patients. In
atherosclerotic disease when the vascular endothelium is damaged prostacyclin
synthesis is decreased and thromboxane A2 production increases. Prompted by this
knowledge of the importance of prostacyclin in pathogenesis of atherosclerotic
disease an attempt was made to employ PGI2 clinically--for treatment of advanced
forms of peripheral arterial atherosclerotic disease. Favourable effects of the
stable analogue of prostacyclin (Iloprost), were reported in various studies,
which included patients with peripheral atherosclerotic arterial disease,
thromboangiitis obliterans and Raynaud's phenomenon. The use of Iloprost resulted
in a significantly superior response than other drugs and placebo in terms of
alleviation of rest pain, ulcer healing and decrease of amputation rate of
ischaemic limbs. Therefore prostacyclin provides a therapeutic option in patients
with advanced forms of arterial disease--including critical ischaemia.
PMID- 11005644
TI - Lacidipine decreases the honeybee venom-induced vasoconstriction of the isolated
porcine coronary artery.
AB - The venom of the honeybee Apis mellifera induces cardiovascular dysfunction. As
its effects on coronary arteries have not yet been described, we studied the
effects of the whole honeybee venom (non-volatile part) in the isolated porcine
left anterior descending coronary artery (LAD) and the influence of L-type Ca2+
channel blocker, lacidipine, upon the venom effects in LAD. The venom produced
concentration dependent contractions (7-70 microg/ml) of the porcine LAD; maximal
effect of the venom was approximately the same as the effect of 30 mM KCl.
Lacidipine concentration dependently (0.1-10 microM) and significantly (P < or =
0.05) decreased the venom-induced vasoconstriction. The results indicate the
involvement of L-type Ca2+ channels in coronary contraction, induced by bee
venom.
PMID- 11005645
TI - Effects of mibefradil and verapamil on ischemic-reperfusion in the hearts of
guinea pigs with acute renal failure.
AB - Two parameters indicating the ischemic-reperfusion myocardial injury, coronary
flow and lactate dehydrogenase (LDH) release rate, were evaluated in guinea pigs
with gentamicine-induced acute renal failure (ARF) and compared with those of
healthy animals. Isolated Langendorffs hearts were exposed to 50 min of zero-flow
global ischemia and 60 min of reperfusion. The influences of calcium channel
antagonists (of T- and L-type antagonist mibefradil and of L-type antagonist
verapamil) in reperfusion solution were evaluated. Our results showed coronary
dilatation and higher LDH release rate in ARF than in control hearts before
ischemia. Recovery of coronary flow during reperfusion was better and LDH release
rate lower in ARF vs. control hearts. Perfusion with mibefradil and verapamil did
not additionally increase coronary flow, however 0.1 microM mibefradil and
verapamil decreased LDH release rate during reperfusion in ARF hearts in
comparison to control hearts. Our results showed some protective effects of 0.1
microM mibefradil and verapamil on LDH release rate during reperfusion, but not
on coronary flow in guinea pigs hearts with ARF.
PMID- 11005646
TI - Thermal conductivity of the porcine heart tissue.
AB - The porcine heart was used as a model for studying the thermal changes in
myocardium at cooling and re-warming during open heart surgery. A section of the
heart septum was excised and tissue was cut into two similar square slices. The
same shape of the tissue, cut from the surface from the upper lateral wall of the
left ventricle, covered with epicardium and fat, was taken for another
measurement. A thin (<0.5 mm) square thermal source of the same length of the
side as the tissue samples was put between the two slices of tissue. This set was
placed in the middle of two identical copper cylinders (2r=50 mm, height=55 mm)
used to keep the outer side of the specimen at controlled room temperature.
Thermal conductivity of the heart tissue was determined at controlled thermal
power, and known difference of the temperature at the edge of the tissue and at
the middle of the heater, when steady state was reached. Thermal conductivity
calculated from the temperature difference and the geometry of heater and samples
was 0.75 W/m.K for septal heart tissue, and 0.60 W/m.K for the lateral wall
ventricle tissue with epicardium and fat.
PMID- 11005647
TI - Nicardipine dose-dependently reduces the effect of equinatoxin II on coronary
flow in isolated porcine heart.
AB - Death after i.v. administration of equinatoxin II (EqT II) has been attributed to
the circulatory failure resulting from cardiotoxic effects. The mechanism of
action is unknown. The aim of the present work was to study the effects of the
toxin on vascular tone in the isolated porcine coronary artery and on coronary
flow in the isolated pig heart. EqT II caused concentration-dependent
contractions of rings of the isolated epicardial porcine coronary artery with an
EC50 value of 89+/-5 nM (n=5-6) and maximal effect of about 140% of the
contraction induced by 20 nM KCl. On Langendorffs porcine heart preparation EqT
II caused a dose-dependent decrease of coronary flow. At EqT II doses lower than
0.05 micromol/100 g of heart weight there were no measurable effects of the
toxin. At dose 0.5 micromol/100 g the toxin decreased coronary flow to less than
9.8+/-2.5% of the control value. The constrictory effect of the toxin on isolated
porcine coronary arteries was diminished by the L-type calcium channel antagonist
nicardipine (NC). NC in 1 microM concentration almost completely abolished the
effect of EqT II on coronary flow. Our results confirmed involvement of L-type
calcium channels in the vasoconstrictory effects of EqT II on epicardial coronary
arteries.
PMID- 11005648
TI - Action of mibefradil and lacidipine on the isolated human anterior tibial artery.
AB - In isolated human anterior tibial artery the effects of two different types of
calcium channel antagonists, mibefradil (a selective T-type Ca2+ channel
antagonist) and lacidipine (a 1,4 dihydropyridine Ca2+ channel antagonist, acting
at L- and T-type, but binds preferentially at L-type Ca2+ channels) were
compared. Both drugs reduced the contractions of isolated arteries induced by 60
mM KCl. The potency (IC50) of mibefradil was 6.5 microM and of lacidipine 82.4
nM. The potencies of both Ca2+ channel antagonists differed significantly
(p<0.001 at 0.1 and 1 microM; p<0.01 at 10 microM). Lacidipine was 79-times more
effective than mibefradil in reducing the vasoconstriction in isolated human
anterior tibial artery. One of the reasons for higher potency of lacidipine could
be a higher density of L-type than of T-type Ca2+ channels in tissue of the human
anterior tibial artery.
PMID- 11005649
TI - Comparison of effects of nitrendipine, lacidipine and mibefradil on postischaemic
myocardial damage in isolated rat hearts.
AB - During ischaemia and reperfusion increased cytosolic Ca2+ is one of the important
causes for ischaemic-reperfusion myocardial injury. In the present study we
compared effects of preferentially L-type Ca2+ antagonists nitrendipine (NT) and
lacidipine (LP), and of mibefradil (MB) a Ca2+ antagonist with higher affinity to
T- than to L-type channels on myocardial function during reperfusion. Coronary
flow (CF), heart rate (HR), left ventricular pressure (LVP), lactate
dehydrogenase (LDH) release rate and ECG were registered during 40 min of
reperfusion following 30 min of global zero flow ischaemia in Langendorff's
isolated rat hearts. Either NT (100 nmol/L) or LP (10 nmol/L) or MB (100 nmol/L)
was added to Krebs-Henseleit solution 10 min before ischaemia till the end of
experiments. All three drugs influenced CF, HR and LVP. All of them decreased LDH
release rate (P < 0.05, in microkat/g x min) when compared with control hearts
(53.2 +/- 5.1): MB (19.4 +/- 4.3) > LP (30.7 +/- 6.6) > NT (43.3 +/- 2.8). NT
reduced the duration of continuous arrhythmias at the beginning of reperfusion
(to 59.1 +/- 6.1% of ischaemic controls) as well as the number of single
arrhythmic events arising during the whole period of reperfusion (to 26.1 +/-
6.0% of ischaemic controls). MB diminished only single arrhythmic events during
reperfusion to 39.1 +/- 17.3% of ischaemic controls. LP did not affect the onset
of arrhythmias. Results of our experiments indicate a relatively greater
importance of T-type than of L-type Ca2+ channels in the arising of postischaemic
myocardial damage.
PMID- 11005650
TI - The importance of hemolysis in the lethal effects of equnatoxin II, a protein
from the sea anemone Actinia equina (L.).
AB - Equinatoxin II (EqT II) is one of the three isotoxins isolated from the sea
anemone Actinia equina (L). The cause of death due to i.v. application of Eq T II
was attributed to its hemolytic activity and hiperkaliemia, and the direct cardio
respiratory effects of the toxin. The toxin also binds to plasma lipids and forms
toxic conglomerates with them. In our study we tried to evaluate the importance
of interaction of the toxin with blood components in the toxin lethality.
Anaesthetized male Wistar rats were used. The respiratory activity, ECG and
animal serum ionic composition were monitored. To simulate isolated effects of
the toxin hemolytic activity, hemolysed erythrocytes, KCl and mixture of rat
serum with the toxin were injected i.v.. It was shown that neither the lysed
erythrocytes nor the mixture of rat serum with the toxin were lethal for the
experimental animals. Even KCl, in concentrations detected in serum of rats
killed by the toxin, did not cause the death of experimental animals. Our results
indicate that either a combination of the tested effects of the toxin on blood
components or more probably the direct effects of the toxin on vital organs are
responsible for the toxin lethality.
PMID- 11005651
TI - Assessment of kainate toxicity using contrast enhanced magnetic resonance
imaging.
AB - The purpose of this study was to test the capability of contrast enhanced
magnetic resonance imaging (MRI) in assessing lesion formation in rat brain after
systemic (i.v.) administration of kainate. MRI was performed with T1-weighted
spin echo sequence before and after the administration of kainate and contrast
media. Contrast media used were based on paramagnetic gadolinium (III) ion: Gd
DTPA (gadoliniumdiethylenetriaminepentaacetic acid) and prototype agents for
blood-pool enhancement. Gadomer-17 and polylysine-Gd-DTPA. Enhancement of lesion
rims and other brain tissue abnormalities due to kainate with Gd-DTPA, Gadomer-17
and polylysine-Gd-DTPA were observed mainly in the region of hippocampus and in
the areas not protected by the blood-brain-barrier (BBB).
PMID- 11005652
TI - Alpha-melanocyte stimulating hormone desensitizes the responsiveness of carbon
fibres within seconds.
AB - We monitored electrooxidation of noradrenaline and alpha-melanocyte stimulating
hormone (alpha-MSH) at a carbon-fibre microelectrode (CFME). The solution of
noradrenaline (1 mM) or alpha-MSH (1 mM) was applied by a pressure pulse (2 s)
from a micropipette to a voltage-clamped (850 mV) CFME immersed into bathing
solution of an inverted microscope chamber. The distance between the CFME and
micropipette was 2 to 12 microm. The maximal currents recorded for these two
agents were 8.0 +/- 0.5 pA (N = 9) and 3.0 +/- 1.1 pA (N = 9), respectively.
Pressure application of control solution did not affect the measured current. The
noradrenaline-evoked anodic current was characterized by a monotonic increase
that attained the maximum at the end of the pressure pulse. In contrast, the time
course of the alpha-MSH-evoked current was biphasic. The maximum amplitude of
this current was attained in 0.59 +/- 0.15 s (N = 9) and then it declined with a
time constant of 7.5 +/- 4.0 s (N = 9) until the pressure pulse was terminated.
We explain this phenomenon to be due to an interaction between the peptide
oxidation products and the CFME which results in its desensitization.
PMID- 11005653
TI - Selective recording of neuroelectric activity from the peripheral nerve.
AB - Electroneurograms (ENGs) from superficial regions of the sciatic nerve of a dog,
innervating the tibialis anterior (TA) and gastrocnemius muscles (GM), arising
mainly from muscle spindles and Golgi tendon organs were recorded selectively
with an implanted 33-electrode spiral cuff (cuff). Relative positions of
superficial regions within the cuff were defined by delivering stimulating pulses
on groups of three electrodes (GTEs) within the cuff which were in contact with
them. It was found that GTEs eliciting maximum contractions of muscles were GTE
No. 3 for the TA muscle and GTE No. 8 for the GM muscle. In the first experiment
the implanted leg was mounted into a special electronic brace. Extending forces
were applied to the ankle rotating it by up to +/-37 degrees according to the
neutral position, thus eliciting torques in the TA muscle of up to 1.2 Nm.
Channel 1 of the 4-channel preamplifier was connected to GTE No. 8, channel 2 to
GTE No. 2, channel 3 to GTE No. 11 and channel 4 to GTE No. 5. Results show that
only ENG recorded with GTE No. 8, being close to the region innervating the TA
muscle, correspond to the mechanical load. In the second experiment the calcanean
tendon (CT) of an implanted leg was dissected. The proximal end of the CT was
connected to a force transducer and repetitive pull forces (about 12 N) were
applied to the CT. Channel 1 of the preamplifier was connected to GTE No. 5,
channel 2 to GTE No. 1, channel 3 to the GTE No. 11 and channel 4 to GTE No. 8.
Results show that only ENG recorded with GTE No. 5, being close to the region
innervating the GM muscle, correspond to the mechanical load applied on CT.
PMID- 11005654
TI - Seizure-induced changes in energy metabolites and effects of N-tert-butyl-alpha
phenylnitrone (PNB) and vitamin E in rats.
AB - Impaired energy metabolism may play a critical role in the neuronal injury caused
by kainic acid (KA) induced status epilepticus (SE). Following an acute dose of
KA (15 mg/kg, s.c.) rats developed SE within 1 h. Rats were sacrificed 1 or 72 h
after the onset of SE using a head focused microwave technique and the brain
regions (pyriform cortex, amygdala, and hippocampus) were assayed for energy
metabolites: ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) using
reversed-phase HPLC (RP-HPLC). Control values were significantly higher in cortex
(23-32%) than in other brain regions. Within 1 h, SE caused a marked decline in
ATP (44-56%), PCr (49-64%), total adenine nucleotides (TAN, 45-50%) and total
creatine compounds (TCC, 32-51%). Within three days, the hippocampus showed the
greatest recovery, as the reduced values returned to normal. Pretreatment of rats
with an antioxidant (PBN, 200 mg/kg, i.p., 30 min prior to KA; or vitamin E (Vit
E), 100 mg/kg, i.p./day for 3 days), which did not prevent seizure activity,
attenuated depletion of high-energy phosphates caused by KA. These findings
suggest that the depletion of energy metabolites caused by KA-induced seizures
may be linked to oxidative stress mediated toxicity.
PMID- 11005655
TI - Neurotransplantation-induced plasticity in the recipient CNS: focusing on the
recipient response.
AB - In the last two decades, neurotransplantation has gained the status of a
potentially valuable treatment option in various central nervous system (CNS)
disorders. This technique has provided considerable functional improvement in
animal models of neurodegenerative diseases, stroke and trauma. In order to make
the best therapeutic use of this treatment option, mechanisms of
neurotransplantation-induced recovery need to be better understood. Specific
interactions of transplants with the recipient brain, which are prominent in
embryonic neural cell grafts, include formation of synapses between grafted
neurons and recipient neuronal population with controlled release of
neurotransmitters. Production and release of specific trophic substances for the
recipient neurons by the grafted cells also play a considerable role in some
transplants. In the above cases, the functional recovery seems to correlate well
with the number of surviving cells in the transplant. There is, however, another
component to the graft-induced recovery, best revealed in those graft recipients
who display functional improvement although only few or no grafted cells can be
found at the post mortem analysis. While psychological factors (placebo effect)
have been proposed to play a central role in human graft recipients with
functional recovery in the absence of surviving grafts, animal models of
neurodegenerative disease have consistently shown the same phenomenon. Our recent
results point to the local inflammatory and immune response to transplantation as
a key element which induces a trophic response in the CNS parenchyma and
stimulates plastic changes of the recipient neural connections. Findings by other
investigators, who studied the connections between the inflammatory and
neurotrophic responses in vitro and in vivo, and glial reaction to CNS trauma and
trophic factor synthesis in vivo, support such conclusions. Accumulated evidence
point to the need for further studies that would elucidate the role of the immune
response in connection with CNS transplantation outcome.
PMID- 11005656
TI - Biochemical aspects of Salter's osteotomy for treatment of acetabular dysplasia.
AB - The center-edge (CE) angle was measured on serial antero-posterior radiographs of
44 hips treated by Salter's innominate osteotomy for developmental dysplasia of
the hip. Radiographic examination according to Severin was performed and the peak
hip joint pressure was calculated using geometrical parameters determined from
radiographs at the most recent follow-up examination, 7 to 13 years
postoperatively. At the latest follow-up assessment, there was a positive
correlation between the postoperative CE angle and radiographic results. Negative
correlation was found between the postoperative CE angle and peak hip joint
pressure at the latest follow up. In conclusion, Salter's osteotomy performed to
treat developmental dysplasia of the hip should involve radical acetabular
correction resulting in maximum increase of the CE angle.
PMID- 11005657
TI - The development of the method for the determination of terbinafine in cat's
plasma and hair.
AB - Clinical investigations of terbinafine indicate its high treatment activity
against infections by several dermatophytes. Its efficiency was tested also in
the treatment of microsporosis in cats. The distribution of terbinafine in cat's
plasma and hair is important for the identification of the drug efficiency. A
fast and reliable reversed-phase high performance liquid chromatographic method
with appropriate sample preparation has been developed. Reliability, good
reproducibility and low detection limit (LOD 0.25 ng/ml) of the method enable
determination of terbinafine in hair and also in plasma of cats infected with
Microsporum canis treated by Lamisil tablets.
PMID- 11005658
TI - Serum T3 and T4 concentrations in the adult rats treated with herbicide 2,4
dichlorophenoxyacetic acid.
AB - The influence of sublethal doses of 2,4-dichlorophenoxyacetic acid (2,4-D) on
serum T3 and T4 concentrations in Hsd Cpb: Wistar rats of both sexes was studied.
The trial was performed on 24 males and females respectively, each divided into
three groups of 8 animals (control, groups 1 and 2). Aqueous solution of the
compound (11 mg/kg body weight--group 1 and 110 mg/kg body weight--group 2) or
clean tap water (control group) was used. Aliquots of 2.4 ml/kg body weight were
administered with a stomach tube from the 1st to 10th day of the experiment.
Three days before the first treatment and on the 6th and 13th day of the
experiment the serum T3 and T4 concentrations were determined by commercial
radioimmunoassay kits (Byk-Sangtec Diagnostica), validated for rats. A
significant decrease of serum T4 (P < 0.01) and T3 (P < 0.001) was determined in
males of groups 1 and 2 during the experiment. On the 6th day of experiment serum
T4 and T3 values were significantly lower (P < 0.001 and 0.01 respectively) in
group 2 than in the controls and group 1 of both males and females. During the
whole experiment serum T4 levels were lower in females than in males (P < 0.05).
PMID- 11005659
TI - In vivo effects of head-to-tail 3-alkylpiridinium polymers isolated from the
marine sponge Raniera sarai.
AB - Water soluble polymeric 3-alkylpyridinium salts (poly APS; MW 18900 and 5520 Da)
were isolated from the marine sponge Raniera sarai. In vitro it strongly
inhibited acetyl cholinesterase (AChE) from different species (electric eel,
horse serum, human erythrocytes). In our experiments the importance of anti AChE
activity in the toxin lethality was evaluated. In vivo experiments were performed
on male Wistar rats and ECG, blood pressure and breathing pattern were monitored.
After i.v. application of lethal doses of the toxin ECG showed signs of hypo
perfusion. Arterial blood pressure fell to mid-circulatory pressure, and
breathing stopped after a few breaths At sublethal doses the toxin caused an
increase of residual volume, prolongation of expiration, and bradycardia. Patho
anatomical examination revealed that the plugs in lung circulation may cause the
death of experimental animals due to cardiorespiratory failure.
PMID- 11005660
TI - Different operative treatment of slipped capital femoral epiphysis: a comparative
study of biomechanical status of the hip.
AB - The biomechanical status of the hips subject to two different operative
treatments was studied. The biomechanical status was determined by the peak
stress on the weight bearing area using the 3-d mathematical model. It was found
that the procedure according to Imhauser yields considerably and statistically
significantly higher peak stress than the procedure according to Dunn-Fish.
PMID- 11005661
TI - Peak contact stress in human hip during gait.
AB - The contact stress in a human hip is not uniform and it changes with different
body positions. The changing location of the peak contact stress during gait may
indicate the predilection sites for further development of osteoarthritis in the
hip. On the basis of laboratory measurements and by using mathematical models of
forces and stresses in human hip we determined the points of the peak contact
stress in successive phases of gait. Results show that the peak stress points are
mostly located in the posterior-medial portion of the weight bearing area, which
corresponds well to the clinical observations. It is also shown that in the
pathological conditions of hip dysplasia the peak contact stress trajectory is
located more laterally and anteriorly.
PMID- 11005662
TI - G-protein coupled progesterone receptors in the plasma membrane of fungus
Rhizopus nigricans.
AB - We have demonstrated simultaneous existence of progesterone receptors and GTPase
activity in the membranes prepared from the filamentous fungus Rhizopus
nigricans. The results obtained with pertussis toxin treated fungal mycelium
suggest that these receptors do not couple to Gi-Go-proteins and play a role in
the induction of steroid hydroxylating enzyme system by steroid substrates in the
fungus.
PMID- 11005663
TI - The effect of lamina propria on the growth and differentiation of urothelial
cells in vitro.
AB - The effect of lamina propria on the growth and differentiation of the mouse
urinary bladder urothelial cells in vitro has been studied by light and electron
microscopy using morphological and immunohistochemical methods. Three different
types of urothelial cultures were maintained on a porous membrane in serum-free
medium for 10 days. Our results showed that urothelial cells in culture types I
and II were organised as the multilayer epithelium showing terminal
differentiation, from the porous membrane toward the surface. On the surface of
culture type I and II, superficial urothelial cells were highly differentiated.
They formed tight junctions and had plaques of an asymmetric unit membrane, a
hallmark of terminal differentiation in bladder superficial cells. These cultured
superficial cells were also cytokeratin 20 positive. On the contrary, urothelial
cells in culture type III have shown a limited capacity for survival and have
grown as poorly differentiated monolayer. These results revealed that reciprocal
intercellular signalling between the lamina propria and urothelial cells is
essential to achieve terminal differentiation of urothelial cells in vitro.
PMID- 11005664
TI - Mouse urothelial cells in early postnatal development--proliferation and apical
plasma membrane specialization.
AB - The purpose of this work was to investigate proliferation and differentiation of
the mouse urothelial cells from the day of birth until the 5th postnatal day. The
expression of proliferating cell nuclear antigen (PCNA) was studied
immunocytochemically and the differentiation of apical plasma membrane of
superficial cells was analysed by scanning microscopy. It was established that
proliferation activity is very high during all five days since PCNA positive
cells are seen in the superficial and in basal cell layer of the urothelium.
Results of scanning microscopy show that the differentiation of superficial
urothelial cells is a nonsynchronous process, which gradually progresses from the
day of birth and leads into homogeneous population of terminally differentiated
superficial cells on the 5th postnatal day.
PMID- 11005665
TI - Reticulocyte analysis using light microscopy and two different flow cytometric
procedures.
AB - The reticulocyte count is a clinically important indirect indicator of
erythropoietic activity of the bone marrow. Reticulocyte enumeration by light
microscopy is rather inaccurate and has poor reproducibility. Automation of the
reticulocyte count by means of flow cytometry has considerably improved the
quality of this investigation. In our study, we compared three methods of
establishing the blood reticulocyte number: the microscopic brilliant cresyl blue
method and two flow cytometric procedures using thiazole orange (TO), namely
FACSort (Becton-Dickinson) and EPICS Profile (Coulter). The aims of the study
were (1) to select the most suitable TO concentration to be used with the EPICS
Profile cytometer, (2) to determine the correlation between the microscopic
method and the two flow cytometric procedures, and (3) to appraise the
suitability of flow cytometry for reticulocyte analysis in routine clinical work.
According to our results, the most appropriate TO concentration for the EPICS
Profile counter is 0.1 mg/L. We observed a good correlation between the three
methods tested; the correlation coefficients ranged from 0.82 to 0.87. The mean
intra-assay coefficients of variation for the microscopic method and the EPICS
Profile and FACSort procedures were 27.5%, 8.4% and 6.3%, respectively.
PMID- 11005666
TI - The contribution of HLA-Class II antigens in humoral non-response and delayed
response to HBsAG vaccination.
AB - The variability in the immune response modulated by HLA alleles may be an
important factor for the induction of the protective effect of HBsAg vaccines. We
present here the analysis of HLA-DRB1, DQB1 and DQA1 alleles and their
combinations in the group of 36 individuals with poor humoral immmune response to
HBsAg vaccination. Comparison with the control group, consisted of 60 randomly
choosen healthy subjects, revealed that the DRB1*1601, DQB1*0502, DQA1*0102
haplotype is overrepresented in the group of hyporesponders and may therefore be
regarded as a factor influencing poor antibody responsiveness. We observed that
after revaccination two of three individuals who failed to develop anti-HBs
antibodies carry the same phenotype DRB1*0101,DRB1*0301;DQB1*0501,DQB1*0201;DQA1+
++*0101,DQA1*0501, which supports the conjecture that immunogenicity of the HBsAg
vaccine depends on specific combination of HLA DR and DQ molecules on antigen
presenting cells.
PMID- 11005667
TI - Hypomethylation of alphoid DNA and classical satellite DNA on chromosome 1, 9, 16
and Y in extraembryonic tissue.
AB - The pattern of DNA methylation can be analyzed on methaphase chromosomes with
fluorescein labeled antibodies against 5-methylcytosine. In human extraembryonic
tissue lower overall intensity of immunofluorescence in centromeric chromosomal
regions correspond to hypomethylation of the DNA when compared with normal human
lymphocytes. Pericentromeric regions on chromosomes 1,9,16 and heterochromatin on
chromosome Y, which reveal lower levels of immunofluorescence, are rich in
classical satellite DNA type II and III. In our experiment methylation-sensitive
restriction enzymes, alphoid and classical satellite DNA probes specific for
chromosomes 1,9,16 and Y were used. Southern blot analysis on cells from
extraembryonic tissue revealed different extent of hypomethylation in different
chromosomal regions. Our results confirm overall and sequence-specific
hypomethylation of DNA in cells from extraembryonic tissue in comparison with
somatic cells.
PMID- 11005668
TI - Effect of pH on red blood cell deformability.
AB - The effect of pH on the red blood cell (RBC) deformability, which is a
consequence of a change of cell membrane elastic properties is studied
experimentally. With the intention to reduce the effects on deformability of cell
geometry and cytoplasmic viscosity, we measured the deformability of the cells
with the same volume at various pH of cell suspension from 6.2 to 8.0. Constant
cell volume was achieved by varying osmolarity. Deformability was quantified by
measuring the elongation of RBCs subjected to velocity gradient in a transparent
cone-plate rheoscope. Observed significant decrease of deformability at lower pH
leads to the conclusion that membrane elastic properties could be affected by pH
changes in the range from 6.2 to 8.0.
PMID- 11005669
TI - Weak D and partial D in Slovenian population through serology and genotyping.
AB - Weak D red cell phenotype (formerly D(II)) exhibits weaker serological reaction
with anti-D antibodies. Weak D occurs in 0.2% to 1% of whites and is caused by
qualitatively altered RhD proteins called partial D or normal, only weakly
expressed RhD proteins that are called weak D. Partial D genes are hybrid alleles
between RHD an RHCE genes. 23 partial RHD alleles are described. Weak D
phenotypes with reduced expression are likely to possess the normal RHD gene, but
the latest findings indicate that weak D alleles carry at least one point
mutation. The aim of the present work was to answer an important question how to
approach partial and weak D identification in diagnostic use and if it is
possible to distinguish between partial D and weak D using commercially available
anti-D reagents for routine use. We also wanted to evaluate D-screen kit for
partial D identification. We compared phenotypes identified by serological
testing and genotypes identified by RHD Multiplex PCR and D(VII) specific ASPA
PCR. Our results showed that it is not possible to distinguish between partial
and weak D using commercially available anti-D reagents for routine use. D-screen
proved to be useful for D(VI) and D(VII) identification, whereas for partial
D(DFR) identification we must look for another set of monoclonal antibodies or
simply use genotyping methods. In 44 samples with not interpretable serological
results out of 80 we found all RHD specific exons present and we classified the
samples as weak D. Fourteen types of weak D with at least one point mutation were
recently proposed. Designing of allele specific PCRs for identification of
proposed types of weak D is in progress.
PMID- 11005670
TI - Determining the parameters of concentration-response relationship for histamine
on the isolated portion of guinea pig stomach and guinea pig right atrium.
AB - In our previous experiments measuring acid secretion in the isolated mouse
stomach we found higher EC50 values (agonist concentration, evoking half maximal
effect) for histamine than in the experiments on the isolated guinea pig right
atrium (contraction frequency). The difference could be due to nonequilibrium
conditions in the isolated mouse stomach preparation or to species differences.
In order to check this possibility and to test the consistency of concentration
response relationship (CRR) parameter determination on an isolated secretory
organ, we compared EC50 for histamine and pA2 for famotidine on the two isolated
preparations from the same species, guinea pigs. Both, EC50 and pA2 values were
significantly different when measuring gastric acid secretion (9.7 microM and
6.07) from the parameters, found in the isolated right atrium measuring frequency
of contractions (1.6 microM and 7.06). From these results it can be concluded
that the isolated portion of guinea pig stomach is suitable for CRR
determination; but the parameters obtained are in the range of higher
concentrations than the real ones because of kinetic particularities of the
preparation.
PMID- 11005671
TI - The oxygen uptake threshold during incremental exercise test.
AB - The linear relationship between oxygen consumption (VO2) and exercise intensity
is a well established phenomenon observed during incremental exercise. Recently,
a non-linear increase in VO2 has been reported by Zoladz et al., who used a
relatively complicated method to describe the phenomenon. In this study, we tried
to ascertain whether the same phenomenon, which we named the oxygen uptake
threshold (OUT), could be described by a simple method, using the two best
fitting lines adopted for the less and more steep parts of the VO2 increase. Our
hypothesis was that the non-linear VO2 increase was the result of a continuous
VO2 increase (oxygen drift) occurring during the more intense steps only.
Therefore, we analysed the VO2 time course during each step. Six cyclists
performed an incremental exercise test on a cyclo-ergometer. The lactate
threshold (LT) was calculated by using the intersection point of the two best
fitting lines in the diagram of log LA (lactate concentration) dependence on log
P (Power). The time course of VO2 during each step was analysed by an exponential
rise to the maximum model. The results showed that OUT could be determined in
five of the six subjects, whereas LT could be determined in all six subjects. The
power output determined by OUT (168 +/- 13 W) was similar to that determined by
LT (180 +/- 25 W). The VO2 time course during each step showed steady values
during low intensity exercise. At intensities above LT and OUT, however, VO2
increased continuously, showing oxygen drift. It may be concluded that OUT is a
realistic phenomenon, which is based on oxygen drift.
PMID- 11005672
TI - Evaluation of biomechanical status of dysplastic human hips.
AB - The evaluation of the biomechanical status of human hip joint was performed.
Required parameters were assessed from standard antero-posterior rentgenographs
and the value of contact stress on the weight bearing area is calculated. We
analysed 45 dysplastic human hips and compared measured values to 81 healthy
hips. The peak contact stress on the weight bearing area is considerably and
statistically significantly higher in dysplastic hips compared to healthy hips.
The Wiberg centre-edge angle is statistically significantly smaller in group of
dysplastic hips compared to healthy hips.
PMID- 11005673
TI - The influence of the successive depolymerization and polymerization of
cytoskeleton components on the fibroblast shapes.
AB - Monitoring the influence of the cytoskeleton polymers on the shape of
fibroblasts, performing the experiments of repeated degradation and
polymerization of microtubules and microfilaments, we found out that the presence
of microtubules is necessary in order to regenerate the proper functional
structure of microfilaments, and vice versa.
PMID- 11005674
TI - Comparative toxicity of trivalent and pentavalent inorganic and methylated
arsenicals in rat and human cells.
AB - Biomethylation is considered a major detoxification pathway for inorganic
arsenicals (iAs). According to the postulated metabolic scheme, the methylation
of iAs yields methylated metabolites in which arsenic is present in both
pentavalent and trivalent forms. Pentavalent mono- and dimethylated arsenicals
are less acutely toxic than iAs. However, little is known about the toxicity of
trivalent methylated species. In the work reported here the toxicities of iAs and
trivalent and pentavalent methylated arsenicals were examined in cultured human
cells derived from tissues that are considered a major site for iAs methylation
(liver) or targets for carcinogenic effects associated with exposure to iAs
(skin, urinary bladder, and lung). To characterize the role of methylation in the
protection against toxicity of arsenicals, the capacities of cells to produce
methylated metabolites were also examined. In addition to human cells, primary
rat hepatocytes were used as methylating controls. Among the arsenicals examined,
trivalent monomethylated species were the most cytotoxic in all cell types.
Trivalent dimethylated arsenicals were at least as cytotoxic as trivalent iAs
(arsenite) for most cell types. Pentavalent arsenicals were significantly less
cytotoxic than their trivalent analogs. Among the cell types examined, primary
rat hepatocytes exhibited the greatest methylation capacity for iAs followed by
primary human hepatocytes, epidermal keratinocytes, and bronchial epithelial
cells. Cells derived from human bladder did not methylate iAs. There was no
apparent correlation between susceptibility of cells to arsenic toxicity and
their capacity to methylate iAs. These results suggest that (1) trivalent
methylated arsenicals, intermediary products of arsenic methylation, may
significantly contribute to the adverse effects associated with exposure to iAs,
and (2) high methylation capacity does not protect cells from the acute toxicity
of trivalent arsenicals.
PMID- 11005676
TI - Prediction of in vivo metabolic clearance of 25 different petroleum hydrocarbons
by a rat liver head-space technique.
AB - In vitro rates of metabolism and Michaelis-Menten constants were determined for
25 different C6 to C10 hydrocarbons using rat liver slices in a vial head-space
equilibration system. The rates of metabolism were compared with steady-state
levels obtained in vivo in the same strains of rats after inhalation. Aromates
were metabolized at a higher rate than naphthenes n-alkanes, isoalkanes and 1
alkenes. The aromates showed, in contrast to the other hydrocarbons investigated,
increased metabolism with increasing number of carbon atoms up to C8 (o-xylene,
the most extensively metabolized compound). The in vivo steady-state
concentrations of the aromates in blood were inversely related to the in vitro
efficiency of their metabolism. This explains the pattern of blood levels
observed for the C6 to C10 aromates in the rat after inhalation, with o-xylene
demonstrating the lowest concentration. In general, the extent of tissue
metabolism of the investigated hydrocarbons might be of greater importance for
their body distribution than their lipophilicity, especially for the highly
metabolized compounds. The high in vitro intrinsic liver clearances found for the
aromates indicate a flow-dependent metabolism of these hydrocarbons in vivo. The
head-space liver slice equilibration system seems to work adequately for
metabolic studies of hydrocarbons with different volatility and water solubility.
PMID- 11005675
TI - Effects of a cisplatin-chondroitin sulfate A complex in reducing the
nephrotoxicity of cisplatin.
AB - To assess the effects of a macromolecular prodrug in reducing the nephrotoxicity
of cisplatin (CDDP), chondroitin sulfate A (CSA) with a mean molecular weight of
23,000 Da was used to form a complex with CDDP, and the pharmacokinetics and
toxicology of the resulting complex were examined in rats in comparison with
those of CDDP. The total plasma platinum levels and urinary accumulation were
determined up to 3 h following a bolus injection of 2 mg/kg. The results of the
pharmacokinetic analysis showed that the complex suppressed the rapid
distribution of CDDP, decreased the renal clearance and resulted in over fivefold
higher AUC values within 3 h in comparison with CDDP treatment. In addition, the
plasma levels of the drug following administration of the complex decreased
greatly with time throughout the experimental period (3-24 h), whereas a slow
elimination was observed following CDDP administration, which was due to the
irreversible protein binding of CDDP. The tissue-to-plasma partition ratio at 10
min also indicated that the CDDP-CSA complex controlled the perfusion of CDDP to
tissues, especially to the kidney. The accumulation in various tissues was
evaluated at 3 h and 24 h following the injection of 5 mg/kg. Marked differences
in renal accumulation were found within 3 h. Significant reductions in
accumulation in the kidney, lung, muscle and whole blood were found within 24 h
of administration of the complex. The renal toxicity of the CDDP-CSA complex was
evaluated by measuring blood urea nitrogen (BUN), serum creatinine (Cr) and the
ratio of terminal kidney weight to body weight at doses of 2 mg/kg and 5 mg/kg.
The complex displayed a much lower nephrotoxicity at 5 mg/kg in comparison to
CDDP, and similar results were obtained at 2 mg/kg. This suggests that the
complex changed the toxicodynamics of CDDP. Moreover, the anticancer activity of
the CDDP-CSA complex, tested against SW 4800 human colon cancer cells and HeLa
human cervix cancer cells in vitro, showed no decrease as compared with that of
free CDDP. We conclude that the CDDP-CSA complex had the same activity as the
parent drug but showed reduced nephrotoxicity at high doses of CDDP through an
improvement in the pharmacokinetics of CDDP, which resulted from both the
minimization of entry into normal tissues and renal clearance. In addition, it is
also possible that different intracellular interactions in renal cells play a
role in protection against the nephrotoxicity of high doses of CDDP.
PMID- 11005677
TI - Invasion and distribution of methanol.
AB - After the enzyme systems responsible for methanol oxidation were blocked by
ethanol, five test persons were given methanol at a dose of approximately 10
mg/kg weight, once orally and once parenterally. Taking into account the
endogenous blood methanol levels detectable before the administration of
methanol, C0 concentrations of 11.1-15.9 mg/kg were reached. This corresponds to
a distribution volume of approximately 0.77 +/- 0.07 l/kg, which is comparable to
the 0.78 +/- 0.09 l/kg obtained for ethanol. After parenterally administering
methanol as a bolus, the distribution half-life was on average 8 min (range: 3.8
13.8 min). After oral administration of methanol diluted in 100 ml water on an
empty stomach, invasion took place with a half-life of approximately 5 min (3.8
6.9 min). In one case, however, due to vegetative disturbances the invasion half
life was 23.1 min.
PMID- 11005679
TI - Induction of N-nitrosodimethylamine metabolism in liver and lung by in vivo
pyridine treatments of rabbits.
AB - N-Nitrosodimethylamine is a procarcinogen that is activated by cytochrome P450
dependent N-nitrosodimethylamine N-demethylase to labile alpha-carbon
hydroxylated products further resulting in active methylating agents. In vivo
intraperitoneal administration of pyridine to rabbits significantly increased N
nitrosodimethylamine N-demethylase activity by 6.9- and 5.2-fold in liver and
lung microsomes, respectively. Although, p-nitrophenol hydroxylase and aniline 4
hydroxylase activities were markedly enhanced by pyridine treatment in liver
about 4.4- and 5.8-fold, respectively, no change was observed in the activities
of these enzymes in lung microsomes. Pyridine treatment also elevated P450
contents of liver and lung by 2.04- and 1.4-fold, respectively. SDS-PAGE of
pyridine-induced liver microsomes revealed a protein band of enhanced intensity
having Mr of 51,000 migrating in the region of cytochrome P4502E1. The results
obtained in this study demonstrated for the first time, a significant 5.2-fold
induction of NDMA N-demethylase activity in the rabbit lung over the controls.
Pyridine is readily absorbed by inhalation and is a constituent of tobacco and
tobacco smoke. Thus induction of NDMA N-demethylase suggests that in the lung, as
in the liver, pyridine may stimulate the metabolic activation of this nitrosamine
significantly.
PMID- 11005678
TI - Association of azinphos-methyl with rat erythrocytes and hemoglobin.
AB - To investigate whether hemoglobin might serve as a biomarker of exposure to
azinphos-methyl (AZM) encountered by agricultural workers, we exposed rats to
[14C]azinphos-methyl ([14C]AZM). We administered single doses of 1.5 mg/kg, 3
mg/kg, or 6 mg/kg of [14C]AZM by gavage to rats and collected blood 3 days later.
We found a dose-dependent association between radioactivity and erythrocytes and
hemoglobin (measured by liquid scintillation spectrometry). In another
experiment, we administered a single dose of 3 mg/kg [14C]AZM by gavage to rats
and collected blood 3, 11, 15, and 22 days after administration. Radioactivity
continued to be associated with erythrocytes and hemoglobin at all time-points.
Brain and plasma acetylcholinesterase (AChE) activities were not significantly
inhibited, nor did we observe signs of acute toxicity in any of the treated
animals. Loss of radioactivity associated with erythrocytes and hemoglobin over
the study period was consistent with the expected kinetics of erythrocyte
turnover, indicating adduct stability. Approximately 0.49%, 0.43%, 0.39%, and
0.32% of the original radioactivity was recovered in the hemoglobin 3 11, 15, and
22 days, respectively, after administration. These data support our hypothesis
that AZM may form a hemoglobin adduct and may be useful as a biomarker of AZM
exposure.
PMID- 11005680
TI - CYP1A-dependent activation of xenobiotics in endothelial linings of the
chorioallantoic membrane (CAM) in birds.
AB - Metabolic activation of the heterocyclic amine 3-amino -1,4-dimethyl-5 H
pyrido[4,3-b]indole (Trp-P-1) and 7-ethoxyresorufin O-deethylase (EROD) activity
were examined in the chorioallantoic membrane (CAM) of 15-day-old chicken and 18
day-old eider duck embryos. The embryos were pretreated with an Ah receptor
agonist, i.e. beta-naphthoflavone (BNF) or 3,3',4,4',5-pentachlorobiphenyl (PCB
126), or vehicle in ovo. BNF and PCB 126 induced EROD activity and covalent
binding of [3H]Trp-P-1 seven- to tenfold in the CAM of chicken embryos. In the
CAM of eider duck embryos, which are known to be nonresponsive to coplanar PCBs,
PCB 126 treatment had no effect on EROD activity or covalent binding of [3H]Trp-P
1 whereas BNF treatment increased these activities five- and threefold,
respectively. Light microscopic autoradiography was used to identify the cellular
localization of covalent binding of [3H]Trp-P-1 in the CAM. Preferential binding
was observed in endothelial cells in intraepithelial capillaries in the chorionic
epithelium and in blood vessels in the mesenchymal layer. The addition of the
CYP1A inhibitor ellipticine abolished the covalent binding of [3H]Trp-P-1 in the
CAM of BNF- and PCB 126-treated chicken and eider duck embryos. The results
suggest that CYP1A-dependent metabolic activity can be induced in blood vessel
endothelia in the CAM of bird embryos following exposure to Ah receptor agonists
and that the CAM may be a target tissue for CYP1A-activated environmental
pollutants. Furthermore, the highly vascularized CAM could be used as a model for
studies of Ah receptor-mediated alterations in the vasculature.
PMID- 11005681
TI - Polymorphism of the N-acetyltransferase (NAT2), smoking and the potential risk of
periodontal disease.
AB - Periodontal disease is a common multifactorial process that leads to bone
destruction and tooth loss. Interactions of environmental and genetic factors
determine the extent and severity of periodontal disease. Smoking is one of the
risk factors for periodontal disease, and the risk may be influenced by the
polymorphism of N-acetyltransferase (NAT2) via metabolism of smoke-derived
xenobiotics. We therefore hypothesized that a NAT2 genotype would be a risk
factor for periodontal disease. A total of 154 Caucasian subjects were assigned
to one of two groups (1) no or mild and (2) severe periodontal disease based on
radiographic (bone destruction) and clinical criteria (probing depth, attachment
loss) and the number of teeth. In all subjects genotyping for mutations on NAT2
was performed by means of PCR and RFLP analysis. In the less-affected group
genotyping showed a fraction of predicted slow and rapid acetylators (53.6% and
46.4%, respectively) corresponding to the normal distribution in Caucasians.
Severely affected patients were predominantly slow acetylators, the odds ratios
being between 2.38 and 5.02 for the NAT2-related risk depending on the outcome
parameters chosen. Adjustment for age had no influence on these findings. Our
data indicate that the slow acetylator phenotype is associated with a higher risk
of periodontitis, especially with respect to the severity of the disease.
Possible implications with respect to the risk associated with smoking are
discussed.
PMID- 11005682
TI - Statistics and clinical oncology.
PMID- 11005683
TI - Committee on publication ethics (COPE): guidelines on good publication practice.
PMID- 11005684
TI - Randomized trials in early prostate cancer. I: Requiem or renaissance?
PMID- 11005685
TI - Randomized trials in early prostate cancer. II: hormone therapy and radiotherapy
for locally advanced disease: a question is still unanswered. MRC PR07 Trial
Management Group.
PMID- 11005686
TI - Complications of treatment with local field external beam radiotherapy for
localized prostate cancer.
AB - We performed this analysis to document the rate and severity of complications
both during and after local field irradiation for localized prostate cancer and
to assess the influence of three-dimensional conformal radiation therapy (3DCRT)
on these complications. Bowel, urinary and cutaneous toxicities were noted in all
patients treated with primary radiotherapy (RT) for prostate cancer using
Radiation Therapy Oncology Group/European Organization for Research on Treatment
of Cancer scores. Evaluations were performed weekly during RT, 6 weeks after RT
and 3 monthly thereafter. Data on 111 were analysed. We also compared the
complications of conventional and 3DCRT. The serious complication rates
identified in this study compare favourably with those reported in the
literature. Only 3.6%, 0.8% and 0% had acute grade 3 or 4 urinary, bowel or skin
reactions respectively. Only two patients had chronic grade 3 or 4 urinary
complications. Thus far no patients have developed chronic bowel or skin
complications greater than grade 2. Despite dose escalation from 66 Gy to 70 Gy
(with 3DCRT), there was a trend towards reduced toxicity when 3DCRT was compared
with conventional radiation. RT is a well-tolerated treatment for early stage
carcinoma of the prostate and our complication rates are compatible with
international experiences. Further follow-up is required to determine the
efficacy of treatment, the incidence of impotence and the final number of late
complications.
PMID- 11005687
TI - Radiation therapy in localized prostate cancer: long-term results and late
toxicity.
AB - This study was performed to determine the long-term results of radiotherapy in
localized prostate cancer. The frequency and severity of late gastrointestinal
and genitourinary toxicities were also investigated. Between 1980 and 1991, 206
men with localized prostate cancer were treated with radiotherapy alone at our
hospital. Biopsy, transurethral resection of the prostate, or both, confirmed the
diagnosis. Overall survival, cancer-specific survival, disease-free survival,
local recurrence-free survival and metastasis-free survival were determined and
compared with age, stage, grade and diagnostic intervention. A change in
treatment policy occurred in 1987. The treatment results of the two periods are
compared. Late toxicity was registered according to the Radiation Therapy
Oncology Group scale. The 8-year overall survival rates were 60%, 44% and 29% for
Stages T1, T2 and T3 respectively (P=0.028). The 8-year cancer-specific survival
rates were 86%, 66% and 34% for Stages T1, T2 and T3 respectively (P=0.002).
Transurethral resection of the prostate had a negative influence on cancer-free
and disease-free survivals, owing especially to an increased incidence of
metastases. In the bladder and rectum, late toxicity of grade 2 or more occurred
in 26 (13%) of the 199 patients who were alive at 6 months after radiotherapy.
One of these patients developed late toxicity 5 years after the radiotherapy.
Radiation dose and field size had no detectable influence on the development of
late toxicity. The difference between overall survival and cancer-specific
survival confirms that many of these patients die without any clinical signs of
prostate cancer or metastases. This observation puts a question mark over whether
a biochemical endpoint alone is of clinical relevance. Although not statistically
significant, local recurrence-free, disease-free and cancer-specific free
survivals from 1987 onwards improved for larger tumours, which was most likely
due to the administration of higher doses of radiation.
PMID- 11005688
TI - Seminoma metastatic to the prostate resulting in a rectovesical fistula.
AB - We report an unusual presentation of metastatic seminoma within the prostate
gland. Histological diagnosis was obtained using trans-rectal ultrasound guided
prostatic biopsy. The patient developed a rectovesical fistula after ten weeks of
chemotherapy, which healed following a complete radiological response to
treatment
PMID- 11005689
TI - Rare cancers: how should we organize expertise?
PMID- 11005690
TI - Radiation-induced malignant melanoma of the cervix.
AB - We report the occurrence of a malignant melanoma of the uterine cervix in a
patient previously irradiated for a squamous cell carcinoma of the cervix. The
management of malignant melanoma of the cervix is reviewed. The risk of second
cancers in general, malignant melanoma in particular, after radiotherapy for
cervical cancer is also discussed.
PMID- 11005691
TI - Extraosseous osteosarcoma of the penis.
AB - Osteosarcomas have been reported as arising in a number of extraosseous primary
sites, most commonly in the retroperitoneum and the muscles of the thighs and
limb girdles, but also in a variety of other organs. We present a case arising in
the penis, which we believe to be only the fifth reported in the literature and
the only documented long-term survivor. Careful histopathological analysis and
surgical management remain of key importance in the management of all sarcomas
arising in soft tissue.
PMID- 11005692
TI - Oral fluoropyrimidines in the treatment of colorectal cancer.
PMID- 11005693
TI - Radiotherapy is a tolerable and potentially useful therapy in gastric cancer.
AB - The role of radiotherapy in gastric cancer remains controversial. Most previous
clinical trials have not shown any convincing benefit. However, current imaging
is probably sufficiently sophisticated to allow the stomach to be treated
adequately with radiotherapy. Three case histories are presented, which
illustrate the use of radiotherapy in both palliative and radical settings.
PMID- 11005694
TI - Antitumour activity of heparin on metastatic colon cancer.
AB - We present the case history of a 47-year-old patient with metastatic colon
cancer, whose anticoagulant treatment led to a prolonged disease-free survival.
PMID- 11005695
TI - Phase I dose escalation study of gemcitabine and paclitaxel plus colony
stimulating factors in previously treated patients with advanced breast and
ovarian cancer.
AB - Gemcitabine and paclitaxel (PTX) are among the most active new drugs in advanced
breast and ovarian cancer. In this Phase I study, we used fixed doses of
gemcitabine administered on days 1 and 8 and escalating doses of paclitaxel on
day 1 of a 21-day cycle in patients with pretreated metastatic breast or ovarian
cancer. The dose of gemcitabine was fixed at 1,000 mg/m2; PTX was commenced in
the first small patient group at a dose of 90 mg/m2, which was then escalated in
subsequent groups by 30 mg/m2 per step. From the third dose level onwards, all
patients received granulocyte colony-stimulating factor 300 microg by
subcutaneous injection on days 5 and 6, and granulocyte macrophage colony
stimulating factor on days 15-18. Cohorts of at least 3 patients were treated at
each dose level. Dose escalation was stopped if at least a third of the patients
in a given cohort had dose-limiting toxicity (DLT), which was defined as grade 4
neutropenia or thrombocytopenia, or grade 3-4 non-haematological toxicity. The
maximum tolerated dose (MTD) was defined as the dose level immediately below that
causing DLT in one-third of the patients or more. Evaluation of the tumour
response was performed every three cycles. Forty-five patients (31 with breast
cancer, 14 with ovarian cancer) were treated at seven different dose levels. Only
at the seventh PTX dose level was DLT observed after the first course of therapy:
three grade 4 neutropenia, one grade 4 thrombocytopenia, and one grade 4 anaemia.
DLT occurred in 5/6 patients at at PTX dose of 270 mg/m2; therefore dose
escalation was stopped at that level and the dose immediately before it (PTX 240
mg/m2) was considered as the MTD and recommended for further studies. No toxic
deaths occurred. Grade 3-4 uncomplicated neutropenia was observed in four
patients. Three had uncomplicated grade 3-4 thrombocytopenia. One patient had
grade 3 and one grade 4 anaemia. Nonhaematological side effects were generally
mild. Among 30 evaluable patients with metastatic breast cancer, four complete
responses (CR) (13%) and 12 partial responses (PR) (40%) were observed, for an
overall response rate of 53% (95% confidence interval (CI) 34-72). The median
duration of response was 31 weeks. Among 13 evaluable patients with advanced
ovarian cancer, one CR (8%) and five PRs (38%) were observed, for an overall
response rate of 46% (95% CI 19-78). The median duration of response was 32
weeks. Our study shows that gemcitabine and PTX can be administered in
combination in patients with breast and ovarian cancer without unexpected
toxicities and with encouraging therapeutic results.
PMID- 11005696
TI - A multicentre phase II pilot study of epirubicin and Taxol (paclitaxel) in
patients with advanced breast cancer.
AB - Anthracyclines are the gold standard monotherapy for metastatic breast cancer.
Higher response rates are seen with drug combinations, especially with newer
agents such as taxanes. The purpose of this study was to evaluate the toxicity
and activity of the combination of paclitaxel and epirubicin in patients with
advanced breast cancer. Thirty-five women with locally advanced or metastatic
breast cancer (first and second relapse) were treated with epirubicin 75 mg/m2
and paclitaxel 200 mg/m2 3-weekly. Six centres recruited 35 patients; 34 (97%)
were assessable for response. Eighteen had undergone prior chemotherapy,
including six (17%) with anthracycline-containing regimens. Grade 4 neutropenia
was found in 33 patients (94%), which was of 4 days' average duration; however,
infective complications were rare, with only nine cycles (6%) complicated by
neutropenic sepsis. There were two sepsis-related deaths. Symptomatic
cardiotoxicity was infrequent, although a >15% decline in cardiac function was
recorded in five patients (14%). Grade 3 peripheral neuropathy occurred in three
patients (9%). The overall response rate was 50% (95% confidence interval 33-67)
(complete response 12%; partial response 38%), with a median duration of response
of 31 weeks. The median time to progression was 27 weeks, with a median survival
of 48 weeks. This regimen appears to be a relatively safe, tolerable and
effective treatment for advanced breast cancer. A United Kingdom Co-ordinating
Committee for Cancer Research Phase III trial (AB-01) comparing this combination
of epirubicin and paclitaxel with cyclophosphamide and paclitaxel completed
accrual in November 1999.
PMID- 11005697
TI - Unresectable adenoid cystic carcinoma of the trachea treated with
chemoradiotherapy.
PMID- 11005698
TI - Docetaxel-induced radiation recall dermatitis and successful rechallenge without
recurrence.
PMID- 11005699
TI - Evaluation of a nurse-led telephone clinic in the follow-up of patients with
prostate cancer.
PMID- 11005700
TI - Metastatic breast cancer presenting with uveitis.
PMID- 11005701
TI - Is generic prescribing acceptable in epilepsy?
AB - There is considerable debate about the role of generic prescribing for people
with epilepsy. The arguments go beyond simple considerations of cost on one hand
and the possibility of toxicity or loss of seizure control on the other. The
concepts of bioavailability and bioequivalence require further consideration. The
measures that are currently used may not apply equally well to all situations.
For example, additional measures may be needed for controlled-release
preparations and in the other special cases. There is an extensive literature on
the bioequivalence of various phenytoin preparations. This anticonvulsant drug is
poorly soluble in water, has nonlinear kinetics and has a narrow therapeutic
range, implying that problems with bioequivalence are likely to occur. This is
borne out by clinical experience. There are a few published investigations on
carbamazepine. The systematic studies, on the whole, fail to show major
differences in bioequivalence between the various formulations. There is sparse
information on the comparison between generic and proprietary formulations of
other anticonvulsant drugs. Whatever arguments might be put forward supporting
brand name or generic prescribing, there are strong reasons for recommending
tight control on the consistency of anticonvulsant drugs, both generic and
proprietary. There is also a strong case for ensuring that the physician who
signs the prescription remains in control of the situation and that any decisions
that the physician makes should be based on accurate and reliable information.
PMID- 11005702
TI - A risk-benefit assessment of risperidone for the treatment of behavioural and
psychological symptoms in dementia.
AB - The importance of behavioural and psychological symptoms in dementia (BPSD) is
increasingly being recognised. Symptoms such as verbal and physical aggression,
agitation, sleep disturbances and wandering are common, cause great distress to
caregivers and are likely to lead to institutionalisation of patients. At
present, these symptoms are also more amenable to treatment compared with the
progressive intellectual decline caused by dementing illnesses. The care of
individuals with BPSD involves a broad range of psychosocial treatments for the
patient and his or her family. If pharmacotherapy is deemed necessary to manage
BPSD, a careful balance must be struck between the benefits of symptom control
and the inherent risks associated with most psychotropic agents in the elderly.
Elderly patients in general, and patients with dementia in particular, are more
sensitive to medication adverse effects, including anticholinergic effects,
orthostatic hypotension, sedation, parkinsonism, tardive dyskinesia and cognitive
impairment than younger patients with dementia or individuals without dementia.
To date, treatment of symptoms of aggression and psychosis has relied on the
empirical use of antidepressants, anxiolytics, typical antipsychotics
(neuroleptics) and other agents. Treatment-limiting adverse effects are
frequently reported with all of these agents. However, it is the typical
antipsychotics and the atypical antipsychotic clozapine that are associated with
the greatest risk of adverse effects in the elderly. The present review
highlights the issues that limit the use of older psychotropic agents in the
elderly, and presents an assessment of the available evidence concerning the
efficacy, safety and tolerability of the atypical antipsychotic risperidone, in
the treatment of BPSD in elderly patients with dementia. The extensive clinical
development programme for risperidone has shown the drug to be effective and well
tolerated in many fragile patients. As a result of its efficacy and safety
profile, risperidone can be used for the treatment of behavioural and
psychological symptoms in patients with dementia. Risperidone therefore
represents a significant addition to the armamentarium for BPSD. While efforts
continue in the development of treatment for the cognitive decline associated
with dementia, treatment is now available for the noncognitive symptoms. By
treating the latter, risperidone has the potential to be of substantial benefit
to patients with dementia, their carers and the costs of healthcare.
PMID- 11005703
TI - Comparative tolerability of the HMG-CoA reductase inhibitors.
AB - The availability of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
inhibitors has revolutionised the treatment of lipid abnormalities in patients at
risk for the development of coronary atherosclerosis. The relatively widespread
experience with HMG-CoA therapy has allowed a clear picture to emerge concerning
the relative tolerability of these agents. While HMG-CoA reductase inhibitors
have been shown to decrease complications from atherosclerosis and to improve
total mortality, concern has been raised as to the long term safety of these
agents. They came under close scrutiny in early trials because ocular
complications had been seen with older inhibitors of cholesterol synthesis.
However, extensive evaluation demonstrated no significant adverse alteration of
ophthalmological function by the HMG-CoA reductase inhibitors. Extensive
experience with the potential adverse effect of the HMG-CoA reductase inhibitors
on hepatic function has accumulated. The effect on hepatic function for the
various HMG-CoA reductase inhibitors is roughly dose-related and 1 to 3% of
patients experience an increase in hepatic enzyme levels. The majority of liver
abnormalities occur within the first 3 months of therapy and require monitoring.
Rhabdomyolysis is an uncommon syndrome and occurs in approximately 0.1% of
patients who receive HMG-CoA reductase inhibitor monotherapy. However, the
incidence is increased when HMG-CoA reductase inhibitors are used in combination
with agents that share a common metabolic path. The role of the cytochrome P450
(CYP) enzyme system in drug-drug interactions involving HMG-CoA reductase
inhibitors has been extensively studied. Atorvastatin, cerivastatin, lovastatin
and simvastatin are predominantly metabolised by the CYP3A4 isozyme. Fluvastatin
has several metabolic pathways which involve the CYP enzyme system. Pravastatin
is not significantly metabolised by this enzyme and thus has theoretical
advantage in combination therapy. The major interactions with HMG-CoA reductase
inhibitors in combination therapy involving rhabdomyolysis include fibric acid
derivatives, erythromycin, cyclosporin and fluconazole. Additional concern has
been raised relative to overzealous lowering of cholesterol which could occur due
to the potency of therapy with these agents. Currently, there is no evidence from
clinical trials of an increase in cardiovascular or total mortality associated
with potent low density lipoprotein reduction. However, a threshold effect had
been inferred by retrospective analysis of the Cholesterol and Recurrent Events
study utilising pravastatin and the role of aggressive lipid therapy is currently
being addressed in several large scale trials.
PMID- 11005704
TI - Cardiovascular adverse effects of antipsychotic drugs.
AB - Minor cardiovascular adverse effects from antipsychotic drugs are extremely
common. They include effects such as postural hypotension and tachycardia due to
anticholinergic or alpha1-adrenoceptor blockade, and may occur in the majority of
patients at therapeutic dosages. There are a number of pharmacological effects
that are of uncertain clinical significance, such as blockade of calmodulin,
sodium and calcium channels and alpha2-adrenoceptors in the central nervous
system. The most serious consequences of treatment, arrhythmias and sudden death,
are probably uncommon and are most likely to be caused primarily by blockade of
cardiac potassium channels such as HERG. Incomplete evidence suggests that
arrhythmias and sudden death are a particular problem with certain drugs
(thioridazine and droperidol), high risk populations (elderly, pre-existing
cardiovascular disease, inherited disorders of cardiac ion channels or of
antipsychotic drug metabolism) or people taking interacting drugs (such as drugs
that prolong the QT interval, e.g. tricyclic antidepressants, drugs that inhibit
antipsychotic drug metabolism, or diuretics). Clozapine may be unique in also
causing death from myocarditis and cardiomyopathy. Much further research is
required to more clearly identify high risk drugs and the populations that are at
risk of sudden death, as well as the mechanisms involved and the extent of the
risk.
PMID- 11005706
TI - Risk classification systems for drug use during pregnancy: are they a reliable
source of information?
AB - BACKGROUND: In several countries, risk classification systems have been set up to
summarise the sparse data on drug safety during pregnancy. However, these have
resulted in ambiguous statements that are often difficult to interpret and use
with accuracy when counselling patients on drug use in pregnancy. OBJECTIVES: The
objective of this study was to compare and analyse the consistency between and
the criteria for risk classification for medications used during pregnancy
included in 3 widely used international risk classification systems. All 3
systems use categories based on risk factors to summarise the degree to which
available clinical information has ruled out the risk to unborn offspring,
balanced against the drug's potential benefit to the patient. METHODS: Drugs
included in the risk classification systems from the US Food and Drug
Administration (FDA), the Australian Drug Evaluation Committee (ADEC) and the
Swedish Catalogue of Approved Drugs (FASS), were reviewed and compared on basis
of the risk factor category to which they had been assigned. Agreement between
the systems was calculated as the number of drugs common to all 3 and assigned to
the same risk factor category. In addition, evidence on teratogenicity and
adverse effects during pregnancy was retrieved using a MEDLINE search (from 1966
up to 1998) for common drugs classified as teratogenic. RESULTS: Differences in
the allocation of drugs to different risk factor categories were found. Risk
factor category allocation for 645 drugs classified by the FDA, 446 classified by
ADEC and 527 classified by FASS was compared. Only 61 (26%) of the 236 drugs
common to all 3 systems were placed in the same risk factor category. Analysis of
studies on the safety of common drugs during pregnancy of drugs classified as X
by the FDA indicated that the variability in category allocation was not only
attributable to the different definitions for the categories, but also depended
on how the available scientific literature was handled. CONCLUSIONS: Differences
in category allocation for the same drug can be a source of great confusion among
users of the classification systems as well as for those who require information
regarding risk for drug use during pregnancy, and may limit the usefulness and
reliability of risk classification systems.
PMID- 11005705
TI - Drug therapy for hyperthyroidism in pregnancy: safety issues for mother and
fetus.
AB - Hyperthyroidism (thyrotoxicosis) in pregnancy and the child bearing years is
usually attributable to Graves' disease. This is an autoimmune condition in which
thyroid-stimulating immunoglobulins (TSI) cause hyperthyroidism. As a rule,
pregnancy complicates the management of hyperthyroidism, rather than vice versa.
However, patients who remain thyrotoxic during pregnancy are at increased risk of
maternal and fetal complications, particularly miscarriage and stillbirth.
Therefore, bodyweight loss, eye signs and a bruit over the thyroid gland in a
pregnant woman warrant thyroid investigation. Investigations should include
measurement of serum free thyroid hormone levels [free thyroxine (T4) and free
triiodothyronine (T3)] rather than total T4 and T3 levels, because total T4 and
T3 levels may be raised in euthyroid pregnancies due to the presence of increased
levels of thyroxine binding globulin (TBG). By 20 weeks' gestational age, the
fetal thyroid is fully responsive to TSI and to antithyroid drugs. Maternal T4
and T3 and thyrotropin pass across the placenta in small and decreasing amounts
as gestation progresses, but thyrotropin releasing hormone, TSI, antithyroid
drugs, iodides and beta-blockers are readily transferred to the fetus from the
mother. Hyperthyroidism is usually treated throughout pregnancy with an
antithyroid drug, preferably propylthiouracil. The smallest dose which controls
the disease is given with careful monitoring of free T4 and T3 levels to minimise
the risk of fetal hypothyroidism and goitre. Bilateral subtotal thyroidectomy may
be an option for a small number of patients with hyperthyroidism in pregnancy.
PMID- 11005707
TI - If bone is the answer, then what is the question?
AB - In the 19th century, several scientists attempted to relate bone trabecular
morphology to its mechanical, load-bearing function. It was suggested that bone
architecture was an answer to requirements of optimal stress transfer, pairing
maximal strength to minimal weight, according to particular mathematical design
rules. Using contemporary methods of analysis, stress transfer in bones was
studied and compared with anatomical specimens, from which it was hypothesised
that trabecular architecture is associated with stress trajectories. Others
focused on the biological processes by which trabecular architectures are formed
and on the question of how bone could maintain the relationship between external
load and architecture in a variable functional environment. Wilhelm Roux
introduced the principle of functional adaptation as a self-organising process
based in the tissues. Julius Wolff, anatomist and orthopaedic surgeon, entwined
these 3 issues in his book The Law of Bone Remodeling (translation), which set
the stage for biomechanical research goals in our day. 'Wolff's Law' is a
question rather than a law, asking for the requirements of structural
optimisation. In this article, based on finite element analysis (FEA) results of
stress transfer in bones, it is argued that it was the wrong question, putting us
on the wrong foot. The maximal strength/minimal weight principle does not provide
a rationale for architectural formation or adaptation; the similarity between
trabecular orientation and stress trajectories is circumstantial, not causal.
Based on computer simulations of bone remodelling as a regulatory process,
governed by mechanical usage and orchestrated by osteocyte mechanosensitivity, it
is shown that Roux's paradigm, conversely, is a realistic proposition. Put in a
quantitative regulatory context, it can predict both trabecular formation and
adaptation. Hence, trabecular architecture is not an answer to Wolff's question,
in the sense of this article's title. There are no mathematical optimisation
rules for bone architecture; there is just a biological regulatory process,
producing a structure adapted to mechanical demands by the nature of its
characteristics, adequate for evolutionary endurance. It is predicted that
computer simulation of this process can help us to unravel its secrets.
PMID- 11005708
TI - Regression of blood vessels in the ventral velum of Xenopus laevis Daudin during
metamorphosis: light microscopic and transmission electron microscopic study.
AB - Structural changes of the ventral velum of Xenopus laevis tadpoles from late
prometamorphosis (stage 58) to the height of metamorphic climax (stage 62) were
examined by light and transmission electron microscopy. Special emphasis was
given to the blood vessel regression. Early changes of velar capillaries were
formation of luminal and abluminal endothelial cell processes, vacuolation, and
cytoplasmic and nuclear chromatin condensation. At the height of metamorphic
climax, transmission electron microscopy revealed apoptotic endothelial cells
with nuclear condensation and fragmentation, intraluminal bulging of rounded
endothelial cells which narrowed or even plugged the capillary, and different
stages of endothelial cell detachment ('shedding') into the vessel lumen. These
changes explain the 'miniaturisation' of the velar microvascular bed as well as
the typical features found in resin-casts of regressing velar vessels which have
been observed in a previous scanning electron microscopy study of the ventral
velum.
PMID- 11005709
TI - Structural and spatial organisation of brain parenchymal vessels in the lizard,
Podarcis sicula: a light, transmission and scanning electron microscopy study.
AB - The structure and 3-dimensional pattern of the intraparenchymal microvessels in
the brain of the lizard, Podarcis sicula, were studied by a combination of light
and transmission electron microscopy as well as scanning electron microscopy of
vascular corrosion casts. The angioarchitecture pattern consists of narrow
hairpin-shaped microvascular loops of different length originating from the
meningeal surface. In each loop, descending and ascending vessels are closely
apposed to one another throughout their length and are connected by a narrow U
shaped terminal loop at their tips. The 2 limbs of the vessel pairs show a
slightly different diameter but lack other structural differences. While some
paired vessels give rise to a secondary hairpin-shaped loop with 2 possible
branching patterns, there are no anastomotic intraparenchymal connections with
analogous neighbouring structures. The cerebral vascular pattern of Podarcis
sicula resembles that found in a few representatives of other vertebrate classes.
All cerebral vessels structurally appear to be capillaries. Also the observations
carried out on semithin and thin sections strongly support the capillary loop
model in the Podarcis brain vasculature and, in accordance with studies carried
out on various vertebrates, the general submicroscopic features of the brain
capillary wall suggest the presence of an endothelial type blood-brain barrier.
PMID- 11005710
TI - Innervation of the cavernous body of the human efferent tear ducts and function
in tear outflow mechanism.
AB - The lacrimal sac and nasolacrimal duct are surrounded by a wide cavernous system
of veins and arteries comparable to a cavernous body. The present study aimed to
demonstrate the ultrastructure of the nervous tissue and the localisation of
neuropeptides involved in the innervation of the cavernous body, a topic not
previously investigated. Different S-100 protein antisera, neuronal markers
(neuron-specific enolase, anti-200 kDa neurofilament), neuropeptides (substance
P, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal
polypeptide) and the neuronal enzyme tyrosine hydroxylase were used to
demonstrate the distribution pattern of the nervous tissue. The ultrastructure of
the innervating nerve fibres was also examined by means of standard transmission
electron microscopy. The cavernous body contained specialised arteries and veins
known as barrier arteries, capacitance veins, and throttle veins. Perivascularly,
the tissue was rich in myelinated and unmyelinated nerve fibres in a plexus-like
network. Small seromucous glands found in the region of the fundus of the
lacrimal sac were contacted by nerve fibres forming a plexus around their
alveoli. Many nerve fibres were positive for S-100 protein (S 100), neuron
specific enolase (NSE), anti-200 kDa neurofilament (RT 97), calcitonin gene
related peptide (CGRP), substance P (SP), tyrosine hydroxylase (TH), and
neuropeptide Y (NPY). Vasoactive intestinal polypeptide (VIP) immunoreactivity
was only demonstrated adjacent to the seromucous glands. Both the density of
nerve fibres as well as the presence of various neuropeptides emphasises the
neural control of the cavernous body of the human efferent tear ducts. By means
of this innervation, the specialised blood vessels permit regulation of blood
flow by opening and closing the lumen of the lacrimal passage as effected by the
engorgement and subsidence of the cavernous body, at the same time regulating
tear outflow. Related functions such as a role in the occurrence of epiphora
related to emotional responses are relevant. Moreover, malfunction in the
innervation of the cavernous body may lead to disturbances in the tear outflow
cycle, ocular congestion or total occlusion of the lacrimal passages.
PMID- 11005711
TI - Differential expression of proteoglycan epitopes by ovine intervertebral disc
cells.
AB - The alginate bead culture system has been utilised by several groups to examine
the in vitro proteoglycan (PG) metabolism of chondrocytes and intervertebral disc
cells, but the nature of the PGs produced has not been examined in detail. This
is largely due to the difficulty of separating the anionically charged sodium
alginate support matrix from PGs which are similarly charged. In the present
study ovine annulus fibrosus, transitional zone and nucleus pulposus cells were
dissociated enzymatically from their respective matrices by sequential digestion
with pronase/clostridial collagenase and DNAase and then cultured in alginate
beads for 10 d. The beads were solubilised and subjected to DEAE Sepharose CL6B
anion exchange chromatography to separate the sodium alginate bead support matrix
material quantitatively from the disc cell PGs. The alginate free bead PGs were
then subjected to composite agarose polyacrylamide gel electrophoresis to resolve
PG populations and the PGs were transferred to nitrocellulose membranes by
semidry electroblotting. The PGs were identified by probing the blots with a
panel of antibodies to defined PG core protein and glycosaminoglycan side chain
epitopes. Alginate beads of disc cells were also embedded in paraffin wax and 4
microm sections cut to immunolocalise decorin, biglycan, versican, and the 7-D-4
PG epitope within the beads. Decorin and biglycan had similar distributions in
the beads, being localised on the cell surface whereas versican and the 7-D-4 PG
epitope were immunolocalised interterritoriarly. This study is the first to
demonstrate that ovine disc cells synthesise versican in alginate bead culture.
Furthermore the immunoblotting studies also showed that a proportion of the 7-D-4
PG epitope was colocalised with versican.
PMID- 11005712
TI - Dynamic ultrastructure of mouse pulmonary alveoli revealed by an in vivo
cryotechnique in combination with freeze-substitution.
AB - A morphological approach to cell dynamics is usually difficult, since routine
preparative techniques for electron microscopy always induce artifacts due to
cessation of the blood supply into organs. An in vivo cryotechnique followed by
the freeze-substitution method probably reduces such problems. It was applied for
examining the pulmonary alveoli of BALB/c mice in vivo. The following
ultrastructural features were revealed. (1) A surfactant layer provided a
continuous covering to the alveolar epithelium. (2) Pleural epithelial cells,
alveolar cells and endothelial cells contained many small vesicles and pits. In
the alveolar epithelium, they were often localised near microtubules. (3) Typical
lamellar structures in large alveolar epithelial cells were rarely detected. (4)
Circulating erythrocytes with various shapes were observed in branching blood
capillaries. (5) A close association between erythrocytes and the endothelium was
seen at the peripheral alveolar septum. Such ultrastructural arrangements may be
appropriate for the physiological functions of the pulmonary alveoli, such as
exchanges of gases or materials in vivo.
PMID- 11005714
TI - Anatomical variations in the human paranasal sinus region studied by CT.
AB - A precise knowledge of the anatomy of the paranasal sinuses is essential for the
clinician. Conventional radiology does not permit a detailed study of the nasal
cavity and paranasal sinuses, and has now largely been replaced by computerised
tomographic (CT) imaging. This gives an applied anatomical view of the region and
the anatomical variants that are very often found. The detection of these
variants to prevent potential hazards is essential for the use of current of
endoscopic surgery on the sinuses. In the present work, we have studied the
anatomical variants observed in the nasal fossae and paranasal sinuses in 110
Spanish subjects, using CT in the coronal plane, complemented by horizontal
views. We have concentrated on the variants of the nasal septum, middle nasal
concha, ethmoid unciform process and ethmoid bulla, together with others of
lesser frequency. The population studied showed great anatomical variability, and
a high percentage (67%) presented one or more anatomical variants. Discounting
agger nasi air cells and asymmetry of both cavities of the sphenoidal sinus,
which were present in all our cases, the variations most often observed were, in
order, deviation of the nasal septum, the presence of a concha bullosa, bony
spurs of the nasal septum and Onodi air cells.
PMID- 11005713
TI - The growth promoting effects of bFGF, PD-ECGF and VEGF on cultured
postimplantation rat embryos deprived of serum fractions.
AB - Serum components in which embryos are cultured in vitro are very important for
normal embryonic development. In this study, rat serum was fractionated using
Macrosep filters to study the effect of a single growth factor. The fractionated
serum, both that containing only material greater than 30 kDa molecular weight (>
30 kDa) and that from which material between 30 kDa and 50 kDa had been removed
(< 30 kDa+ > 50 kDa), caused significant embryonic growth retardation. Addition
of different concentrations of basic fibroblast growth factor (bFGF, 18 kDa),
vascular endothelial growth factor (VEGF, 45 kDa) and platelet-derived
endothelial growth factor (PD-ECGF, 45 kDa), to fractionated serum (bFGF to > 30
kDa serum and VEGF or PD-ECGF to < 30 kDa+ > 50 kDa serum) partially restored
embryonic growth and development according to a morphological scoring system and
protein assay. This restoration was clear by all criteria, as well as in yolk sac
vascularisation and heart development. The growth promoting effects of all 3
factors were significant but did not reach the level seen in embryos grown in
whole rat serum. The effect of these growth factors was also investigated on
anembryonic yolk sac development using a concentration for which maximum whole
embryonic growth was seen (128 ng/ml bFGF, 1.6 ng/ml VEGF and 4 ng/ml PD-ECGF),
and significant anembryonic yolk sac development was found. These findings
suggest that the angiogenic factors may have a growth promoting effect on total
embryonic development and vascularisation.
PMID- 11005715
TI - Ultrastructure of submucosal glands in human anterior middle nasal turbinates.
AB - The abundant glands situated in the lamina propria of the human anterior middle
nasal turbinate were complex tubules that consist of serous, seromucous, and
mucous cells, either singly or in combination. Serous granules were homogeneously
dense, but could have a small lighter core. Seromucous granules had a dense rim
and a large compartment of appreciably lighter density. Gradation between serous
and seromucous granules made precise identification of these secretory cell types
difficult. Mucous cells were of conventional morphology. The secretory tubules,
which possessed a complement of myoepithelial cells, gradually transformed into
ducts or the changeover was relatively sudden. The ductular portions of the
tubules consisted either of tall prismatic cells or of shorter columnar cells,
both of which lacked secretory granules, but had many mitochondria in their
supranuclear cytoplasm. In many cases the ducts, for most of their length,
consisted of secretory cells. These glands clearly participate in the elaboration
of the glycoconjugate coat that serves to protect the nasal mucosa and keeps it
from drying out.
PMID- 11005716
TI - The morphometric changes in the gills of the estuarine crab Chasmagnathus
granulatus under hyper- and hyporegulation conditions are not caused by
proliferation of specialised cells.
AB - Chasmagnathus granulatus is a hyper-hyporegulating crab that inhabits changing
habitats of salinity in Brazil, Uruguay and Argentina. Since the gills are the
main sites for active ion transport in crabs, the adaptive changes in the gill
epithelium occurring under different conditions of salinity were studied by means
of morphological and morphometric analysis, and immunohistochemical
identification of cell proliferation (BrdU technique). In anterior (1-3) gills
the epithelium thickness from crabs acclimatised to 12, 34 and 44 g/l ranged from
1.27 to 2.46 microm, with no significant change during acclimatisation, thus
denoting a respiratory function. Medial (4-5) gill epithelium was slightly
thicker in extreme salinities, but these differences were not statistically
significant. In contrast, epithelial thickness of the posterior (6-8) gills
increased significantly up to 8.10 microm (dorsal zone of gill 8) both in hyper-
and hyposaline media compared with seawater. The dark areas measured in gill 8
treated with AgNO3 revealed putative ion transporting tissue, especially at 12
and 44 g/l, corresponding to the zones of higher epithelial thickness. Hence
these areas seem to participate both in hyper- and hyporegulation. Proliferating
cells labelled with BrdU almost never occurred in the gills/salinity combinations
studied during the initial 48 h of transfer from seawater to hyperconcentrated or
diluted media, thus suggesting an increase in cell size rather than cell
proliferation.
PMID- 11005717
TI - Main trajectories of nerves that traverse and surround the tympanic cavity in the
rat.
AB - To guide surgery of nerves that traverse and surround the tympanic cavity in the
rat, anatomical illustrations are required that are topographically correct. In
this study, maps of this area are presented, extending from the superior cervical
ganglion to the otic ganglion. They were derived from observations that were made
during dissections using a ventral approach. Major blood vessels, bones,
transected muscles of the tongue and neck and supra and infrahyoid muscles serve
as landmarks in the illustrations. The course of the mandibular, facial,
glossopharyngeal, vagus, accessory and hypoglossal nerves with their branches,
and components of the sympathetic system, are shown and discussed with reference
to data available in the literature. Discrepancies in this literature can be
clarified and new data are presented on the trajectories of several nerves. The
course of the tympanic nerve was established. This nerve originates from the
glossopharyngeal nerve, enters the tympanic cavity, crosses the promontory,
passes the tensor tympani muscle dorsally, and continues its route intracranially
to the otic ganglion as the lesser petrosal nerve after intersecting with the
greater petrosal nerve. Auricular branches of the glossopharyngeal and of the
vagus nerve were noted. We also observed a pterygopalatine branch of the internal
carotid nerve, that penetrates the tympanic cavity and courses across the
promontory.
PMID- 11005718
TI - Stereological comparison of 3D spatial relationships involving villi and
intervillous pores in human placentas from control and diabetic pregnancies.
AB - In human placenta, 3D spatial relationships between villi and the maternal
vascular bed determine intervillous porosity and this, in turn, influences
haemodynamics and transport. Recently-developed stereological methods were
applied in order to examine and quantify these relationships. Placentas were
collected after 37 wk from control pregnancies and those associated with maternal
diabetes mellitus classified according to duration and severity (White
classification scheme). Two principal questions were addressed: (1) are normal
spatial arrangements maintained in well-controlled diabetes mellitus? and (2) do
arrangements vary between diabetic groups? To answer these questions, tissue
sections cut at random positions and orientations were generated by systematic
sampling procedures. Volume densities of villi (terminal + intermediate),
intervillous spaces and perivillous fibrin-type fibrinoid deposits were estimated
by test point counting and converted to global volumes after multiplying by
placental volumes. Design-based estimates of the sizes (volume- and surface
weighted volumes) of intervillous 'pores' were obtained by measuring the lengths
of point- and intersection-sampled intercepts. From these, theoretical numbers of
pores were calculated. Model-based estimates (cylinder model) of the hydraulic
diameters and lengths of pores were also made. Second-order stereology was used
to examine spatial relationships within and between villi and pores and to test
whether pair correlation functions deviated from the value expected for 'random'
arrangements. Estimated quantities did not differ significantly between diabetic
groups but did display some departures from control values in non-insulin
dependent (type 2) diabetic placentas. These findings support earlier studies
which indicate that essentially normal microscopical morphology is preserved in
placentas from diabetic subjects with good glycaemic control. Therefore, it is
likely that fetal hypoxia associated with maternal diabetes mellitus is due to
metabolic disturbances rather than abnormalities in the quantities or
arrangements of maternal vascular spaces.
PMID- 11005719
TI - Characterisation of human soft palate muscles with respect to fibre types,
myosins and capillary supply.
AB - Four human soft palate muscles, and palatopharyngeus, the uvula, the levator and
tensor veli palatini were examined using enzyme-histochemical,
immunohistochemical and biochemical methods and compared with human limb and
facial muscles. Our results showed that each palate muscle had a distinct
morphological identity and that they generally shared more similarities with
facial than limb muscles. The palatopharyngeus and uvula muscles contained 2 of
the highest proportions of type II fibres ever reported for human muscles. In
contrast, the levator and tensor veli palatini muscles contained predominantly
type I fibres. A fetal myosin heavy chain isoform (MyHC), not usually found in
normal adult limb muscles, was present in a small number of fibres in all palate
muscles. The mean muscle fibre diameter was smaller than in limb muscles and the
individual and intramuscular variability in diameter and shape was considerable.
All palate muscles had a high capillary density and an unusually high
mitochondrial enzyme activity in the type II fibres, in comparison with limb
muscles. No ordinary muscle spindles were observed. The fibre type and MyHC
composition indicate that the palatopharyngeus and uvula muscles are functionally
involved in quick movements whereas the levator and tensor veli palatini muscles
perform slower and more continuous contractions. The high aerobic capacity and
the rich capillarisation suggest that the palate muscles are relatively fatigue
resistant. Absence of ordinary muscle spindles indicates a special proprioceptive
control system. The special morphology of the palate muscles may be partly
related to the unique anatomy with only one skeletal insertion, a feature
consistent with muscle work at low load and tension and which may influence the
cytoarchitecture of these muscles. Other important factors determining the
special morphological characteristics might be specific functional requirements,
distinct embryological origin and phylogenetic factors.
PMID- 11005720
TI - Positional relationships between the masticatory muscles and their innervating
nerves with special reference to the lateral pterygoid and the midmedial and
discotemporal muscle bundles of temporalis.
AB - For an accurate assessment of jaw movement, it is crucial to understand the
comprehensive formation of the masticatory muscles with special reference to the
relationship to the disc of the temporomandibular joint. Detailed dissection was
performed on 26 head halves of 14 Japanese cadavers in order to obtain precise
anatomical information of the positional relationships between the masticatory
muscles and the branches of the mandibular nerve. After complete removal of the
bony elements, the midmedial muscle bundle in all specimens and the discotemporal
muscle bundle in 6 specimens, derivatives of the temporalis, which insert into
the disc were observed. On the anterior area of the articular capsule and the
disc of the temporomandibular joint, the upper head of the lateral pterygoid, the
midmedial muscle bundle of temporalis and the discotemporal bundle of temporalis
were attached mediolaterally, and in 3 specimens the posterosuperior margin of
the zygomaticomandibularis was attached to the anterolateral area of the disc. It
is suggested that these muscles and muscle bundles contribute to various
mandibular movements. Although various patterns of the positional relationships
between the muscles and muscle bundles and the their innervating nerves are
observed in the present study, relative positional relationships of the muscles
and muscle bundles and of nerves of the mandibular nerve are consistent. A
possible scheme of the developmental formation of the masticatory muscles based
on the findings of the positional relationships between the muscles and the
nerves is presented.
PMID- 11005722
TI - Stereological estimation of volume-weighted mean glomerular volume from arbitrary
sections of the equine kidney.
AB - Mean glomerular volume has previously been estimated, using stereological
techniques, specifically the point-sampled intercept (PSI), either from isotropic
or from vertical sections. As glomeruli are approximately spherical structures,
the same stereological technique was carried out on vertical and arbitrary
sections to determine whether section orientation had any effect on mean
glomerular volume estimation. Equine kidneys from 10 individuals were analysed
using the PSI method of estimating volume-weighted mean glomerular volume (MGV);
for each kidney, arbitrary and vertical sections were analysed. MGVs were not
significantly different between arbitrary and vertical sections (P = 0.691) when
analysing the data with the paired t test; when plotting MGV estimates from
arbitrary sections against those from vertical sections the intercept was found
not to be significantly different from zero (P > 0.8) and the slope of the
regression line not to be significantly different from 1.0 (P > 0.4). For the
estimation of MGV in equine kidneys using PSI, arbitrary sections may be used if
it is not possible to use isotropic or vertical sections, but some caution must
be exercised in the interpretation of results so gained.
PMID- 11005721
TI - Macrophages and apoptosis in the stellate reticulum of the rat enamel organ.
AB - Tooth germs of upper first molars of 1, 3, and 5-d-old rats, fixed in
formaldehyde, were stained for the detection of apoptosis by the TUNEL method,
and by the azo-dye method for the demonstration of acid phosphatase. For
conventional light and electron microscopy the specimens were fixed in
glutaraldehyde-formaldehyde and embedded in glycol methacrylate and Araldite.
Results showed that macrophages, present in the stellate reticulum, contained
basophilic bodies and TUNEL-positive globules, i.e. apoptotic bodies, in their
interior. Macrophages also possessed strong acid phosphatase activity. Electron
microscopy showed the presence of large vacuoles inside the macrophages
containing dense fragmented material. Taken together these results suggest that
the intra-epithelial macrophages of the stellate reticulum engulf apoptotic
bodies.
PMID- 11005723
TI - Variation in shape of the lingula in the adult human mandible.
AB - The lingulae of both sides of 165 dry adult human mandibles, 131 males and 34
females of Indian origin, were classified by their shape into 4 types: 1,
triangular; 2, truncated; 3, nodular; and 4, assimilated. Triangular lingulae
were found in 226 (68.5%) sides, truncated in 52 (15.8%), nodular in 36 (10.9%)
and assimilated in 16 (4.8%) sides. Triangular lingulae were found bilaterally in
110, truncated in 23, nodular in 17 and assimilated in 7 mandibles. Of the
remaining 8 mandibles with different appearances on the 2 sides, 6 had a
combination of triangular and truncated and 2 had nodular and assimilated. The
incidence of triangular and assimilated types in the male and female mandibles
are almost equal. In the truncated type it was double in the male mandibles while
the nodular type was a little less than double in the female mandibles.
PMID- 11005724
TI - The world of oral research: how do we improve it?
PMID- 11005725
TI - Necessary correction of bacterial names?
PMID- 11005726
TI - Biodegradation of Bis-GMA.
PMID- 11005727
TI - A Philadelphia story--featuring Ned Williams: Microbiology at the University of
Pennsylvania School of Dental Medicine.
PMID- 11005728
TI - Interfacial chemistry of the dentin/adhesive bond.
AB - To date, the dentin/adhesive (d/a) bond has primarily been studied by morphologic
analysis in conjunction with bond strength measurement. Although these analyses
have enhanced our understanding, numerous questions about the chemistry have not
been answered. The purpose of this study was to determine, at the molecular
level, quantitative differences in the composition of the d/a interface formed
under "wet" bonding conditions. The occlusal one-third of the crown was removed
from 10 extracted, unerupted human third molars. The prepared dentin surfaces
were treated, per manufacturers' instructions, with either Single Bond (3M) or
One-Step adhesive (Bisco). Three-micron-thick sections of the d/a interface were
cut and stained with Goldner trichrome for light microscopy. Companion slabs were
analyzed with micro-Raman spectroscopy; the sample was placed at the focus of a
100x microscope objective, and spectra were acquired at 1-microm intervals across
the d/a interface. Reference spectra were collected on model compounds of type I
collagen and adhesive; the relative ratios of the integrated intensities of
spectral features from adhesive and collagen were determined and plotted as a
function of wt% adhesive. The same ratios were determined for the interface
samples; by comparing these ratios with the calibration curve generated from the
model compounds, we determined the percent of adhesive as a function of spatial
position across the d/a interface. The relative percent of Single Bond adhesive
was < 50% throughout more than half of the hybrid layer; One Step adhesive was >
or = 50% throughout most of the hybrid. The results from this study provide the
first direct chemical evidence of phase separation in a dentin adhesive and its
detrimental effect on the dentin/adhesive bond.
PMID- 11005729
TI - Temperature dependence of the electrical resistance of sound and carious teeth.
AB - Temperature variations are expected to influence measurement error in electrical
resistance of teeth. It was the aim of this study to determine the changes in
electrical behavior of extracted human teeth due to temperature changes in the
range of room temperature to intra-oral temperature. Nine extracted teeth were
selected, and the occlusal or an approximal surface was chosen for measurement.
Carious involvement of the surfaces ranged from sound to cavitated. Electrical
impedance spectroscopy sweeps in a frequency range of about 100 kHz to 10 Hz were
completed at selected temperatures between 22 degrees C and 40 degrees C. After
fitting the data to equivalent circuits that yielded parameter values for
components of the equivalent circuit, we calculated the dc bulk resistance (Rh).
The temperature dependence of Rb of the surfaces with different carious
involvement was very similar, and the mean drop of Rb from 20 to 35 degrees C was
45% (SD 2%). It was concluded that the electrical resistance of sound and carious
tooth surfaces is inversely related to temperature.
PMID- 11005730
TI - Clinical, radiographic, and genetic evaluation of a novel form of autosomal
dominant oligodontia.
AB - A frameshift mutation recently identified within the paired domain of the
transcription factor, PAX9, has been linked to a unique form of oligodontia in a
single, multigenerational family (Stockton et al., 2000). We now describe the
phenotypic and segregation analyses of this remarkable kindred, the initial
approach taken to identify a candidate gene involved in this form of oligodontia,
and the power of this single-family pedigree to generate significant linkage in a
genome search. Of the 43 family members enrolled in this study, 21 individuals
were affected with several congenitally missing permanent teeth. The pattern of
inheritance of the oligodontia trait suggested the involvement of a single gene
bearing a dominant mutation. To various degrees, affected members lacked
permanent first, second, and third molars in all four quadrants. Several
individuals with missing molars also lacked second premolars- most commonly,
maxillary second premolars and mandibular central incisors. To the best of our
knowledge, this pattern of non-syndromic, familial tooth agenesis has not been
previously described in the literature. Since a missense mutation in the homeobox
gene, MSX1, was previously linked to tooth agenesis in a single family lacking
second premolars and third molars, we performed a mutational analysis of MSX1 by
PCR. The absence of a mutation in exons 1 and 2 of MSX1 suggested that allelic
mutations in the coding region of MSX1 are not associated with this
phenotypically distinct form of oligodontia. Computer simulation of linkage
analysis further proved that this pedigree alone was sufficient to generate a
significant result for a total genome scan.
PMID- 11005731
TI - Unique enamel phenotype associated with amelogenin gene (AMELX) codon 41 point
mutation.
AB - Different mutations in the amelogenin gene (AMELX) result in the markedly
different enamel phenotypes that are collectively known as amelogenesis
imperfecta (AI). We hypothesize that unique phenotypes result from specific
genetic mutations. The purpose of this study was to characterize the enamel
compositional and structural features associated with a specific AMELX mutation
in three families with X-linked AI. We performed mutational analysis by
amplifying AMELX exons and sequencing the products. Permanent and primary
affected (N = 6) and normal (N = 3) teeth were collected and examined by light,
scanning, and transmission electron microscopy. Enamel proteins were evaluated by
immunolocalization of amelogenin and amino acid analysis. AI-affected individuals
all shared a common AMELX point mutation (C to A change at codon 41). The dental
phenotypic findings were remarkably consistent in all affected individuals. The
AI enamel was opaque, with numerous prism defects or holes encompassing the
entire prism width. Affected crystallites appeared more radiolucent and
morphologically less uniform, compared with that of normal enamel. Immunogold
labeling with anti-amelogenin antibodies localized amelogenin to the crystallites
but not to the inter-crystalline spaces. No immunogold labeling was seen in
normal enamel. There was an increased and amelogenin-like protein content in AI
enamel (0.95%) compared with normal enamel (0.13%). We conclude that this codon
41 C to A missense point mutation, in a highly conserved region of the AMELX
gene, results in a remarkably consistent phenotype.
PMID- 11005732
TI - Cementum attachment protein enriches putative cementoblastic populations on root
surfaces in vitro.
AB - We tested the capacity of cementum attachment protein (CAP) to recruit putative
cementoblastic populations to root surfaces in vitro by determining the
phenotypic expression of periodontal ligament cloned cell populations. The clones
were derived from cells that attached to either CAP-coated (experimental) or
uncoated (control) root slices. Root slices were co-cultured with primary human
periodontal ligament cells. Cloned and parent populations were analyzed for their
capacity to express alkaline phosphatase (AP), osteopontin, bone sialoprotein
(BSP), and CAP and to form mineralized tissue in vitro. The percentage of CAP-
and BSP-positive clones was significantly higher in the experimental clones than
in the controls. The percentage of cells positive for AP, BSP, and CAP was higher
in the experimental clones than in their control counterparts. Mineralized tissue
formation was observed only in the cell populations derived from the CAP-coated
root slices. These results indicate that CAP is capable of recruiting putative
cementoblastic populations on root slices in vitro and therefore might play an
important role in cementogenesis during periodontal homeostasis and wound
healing.
PMID- 11005733
TI - Reactive oxygen species participation in experimentally induced arthritis of the
temporomandibular joint in rats.
AB - In the temporomandibular joint (TMJ), it has been hypothesized that mechanical
stresses lead to the oxidative stress of articular tissues. It has also been
postulated that cells pertinent to arthritis-including endothelial cells and
synovial cells-when stimulated by mechanical stresses and/or pro-inflammatory
cytokines, promote oxidative damage. To determine the involvement of reactive
oxygen species (ROS) in the diseased joint, we studied the generation of ROS in
synovial fluid (SF) from interleukin-1alpha (IL-1alpha)-induced TMJ arthritis by
electron spin resonance (ESR) spectroscopy, using the spin trap 5,5-dimethyl-1
pyrroline N-oxide (DMPO). The TMJ arthritis was experimentally induced in rats by
the injection of human recombinant IL-1alpha into the TMJ; control rats were
treated with normal saline solution. We found that the detected radicals in the
collected SF were identified as a 1:2:2:1 quartet, characteristic of the hydroxyl
radical-DMPO spin adduct. The ESR signal intensity of the hydroxyl radical-DMPO
spin adduct in the SF from IL-1-treated rats was significantly higher than that
from the control rats (P < 0.01). The results of ESR study also showed that
hydroxyl radical (HO*) was increased in a time-dependent fashion in the presence
of superoxide anion radical (O2*-) scavenger superoxide dismutase (SOD); the
formation of DMPO-HO* was strongly inhibited by the iron chelater deferoxamine.
We could measure higher levels of free iron (Fe2- and Fe3-) in the SF from TMJ
arthritis than in that from controls (P < 0.05). Analysis of the data obtained
from the present study suggests that the HO* radical detected in SF from IL-1
induced TMJ arthritis is generated via a modified Haber-Weiss reaction
(biological Fenton reaction) in which O2*- can subsequently result in the
production of H2O2 through dismutation reaction by SOD. Thus, HO* may be
generated from the reaction of resultant H2O2 with free iron ions. The results
presented here provide the first evidence of involvement of ROS in IL-1-induced
TMJ arthritis.
PMID- 11005734
TI - Proviral HIV-1 DNA in gingival crevicular fluid of HIV-1-infected patients in
various stages of HIV disease.
AB - The oral cavity is rarely reported to be a site of human immunodeficiency virus
(HIV) transmission, despite detectable virus in saliva and relatively frequent
prevalence of periodontal disease in HIV-infected persons yielding increased
excretion of mononuclear-cell-enriched gingival fluid. To search for possible
sources of HIV in saliva, and using the polymerase chain-reaction technique, we
sought the presence and shedding patterns of proviral HIV-1 DNA in gingival
crevicular fluid in a group of patients previously determined as HIV-1
seropositive. Periodontal status at the collection sites was monitored by several
clinical parameters, including Plaque Index, Gingival Index, probing depth, and
clinical attachment loss. Gingival crevicular fluid samples were collected by
means of paper points. Proviral HIV-1 DNA was detected in the gingival fluid of
17 out of 35 HIV-1-infected patients. Its detection correlated significantly with
higher plasma HIV-1 RNA viral load (p = 0.03) and not with peripheral blood CD4+
cell count, the presence of blood in gingival fluid, or oral lesions. There was a
significant correlation between clinical attachment loss at the sites of fluid
collection and plasma HIV-1 RNA viral load (p = 0.002), and borderline
correlation between the latter and probing depth (p = 0.54) in the group of
patients harboring proviral HIV-1 DNA in gingival crevicular fluid. The results
of our study suggest that mononuclear cells present in gingival crevicular fluid
and harboring proviral HIV-1 DNA could represent a potential source of HIV-1 in
the presence or absence of local bleeding, especially in persons with advanced
HIV infection and increased loss of clinical attachment.
PMID- 11005735
TI - The prevalence of xerostomia and salivary gland hypofunction in a cohort of HIV
positive and at-risk women.
AB - The association of xerostomia and salivary gland hypofunction with HIV infection
has been established for men but not for women. We investigated the prevalence of
these conditions in a national cohort (n = 733) of HIV-positive and at-risk HIV
negative women. Participants in this prospective cross-sectional study were
recruited from the Women's Interagency HIV Study (WIHS) at five outpatient USA
clinics. Xerostomia was assessed based on "yes" responses to a dry-mouth
questionnaire. Samples of unstimulated whole and chewing-stimulated whole saliva
were collected under standardized conditions. The major salivary glands were also
evaluated clinically. The prevalence of dry-mouth complaint, the absence of
saliva upon palpation, and zero unstimulated whole saliva (flow rate = 0 mL/min)
were significantly (p = 0.001) higher in HIV-positive women. Adjusted odds of
zero unstimulated whole saliva were significantly (p = 0.02) higher in HIV
positive women vs. HIV-negative women (OR = 2.86; 95% CI, 1.23 to 6.63).
Significant (p = 0.03) univariate association was found between zero unstimulated
whole saliva and CD4 counts. Adjusted odds of zero unstimulated whole saliva were
significantly (p = 0.02) higher for HIV-positive women with CD4 < 200 compared
with those with CD4 > 500 (OR = 2.61; 95% CI, 1.17 to 5.85). Chewing-stimulated
flow rates were not significantly different between seropositive and seronegative
women. The prevalence of xerostomia and salivary gland hypofunction appears to be
significantly higher in HIV-positive women relative to a comparable group of at
risk seronegative women. Immunosuppression levels measured by CD4 cell counts are
significantly associated with xerostomia and salivary gland hypofunction in a
population of HIV-positive women.
PMID- 11005736
TI - Intra-oral distribution of dental fluorosis in Newburgh and Kingston, New York.
AB - Previous studies of intra-oral distribution of dental fluorosis in low-fluoride
areas reported that teeth that formed later in life were more frequently affected
compared with the early-forming teeth. The steady increase of plasma fluoride
with age, even under constant fluoride exposure, has been suggested as a possible
mechanism for this clinical manifestation. To determine the intra-oral
distribution of Dean's Index scores and the effect of fluoride exposure on early-
and late-forming teeth, we analyzed data collected on 2193 seven- to 14-year-old
lifelong residents of fluoridated or non-fluoridated areas. Logistic regression
procedures were used to determine the effects of fluoridation, early brushing,
daily supplements, and other socio-demographic variables on early- and late
forming teeth. The results show that the occurrence of very mild or greater
levels of fluorosis in the upper anterior teeth was 7 to 10% in the fluoridated
area and 5 to 9% in the nonfluoridated area. In the fluoridated area, the
occurrence of fluorosis increased from anterior to posterior teeth. Both early-
and late-forming teeth were affected by exposure to fluoridation, daily fluoride
supplement use, or brushing before the age of two years. This analysis showed
that the esthetic consequence of exposure to multiple sources of fluoride was
less dramatic, as evidenced by the lower frequency in upper anterior teeth
compared with posterior teeth. The longer maturation process of the posterior
teeth and the thicker enamel appear to be the likely explanation for the higher
occurrence of dental fluorosis in posterior teeth.
PMID- 11005737
TI - Cortical potentials associated with voluntary mandibular movements.
AB - Movement-related cortical potentials (MRCPs) are negative potentials over the
scalp, which gradually increase prior to voluntary movements, and might be
applied to elucidate the cortical efferent function of the mandibular movements.
We compared the MRCPs accompanying various mandibular movements to study the
motor control mechanism underlying these movements. Electroencephalograms (EEGs)
were recorded from 11 electrodes placed over the scalp (F3, Fz, F4, T3, C3, Cz,
C4, T4, P3, Pz, and P4), according to the International 10-20 System, and
electromyograms (EMGs) were obtained from surface electrodes over the masseter
muscle and the anterior belly of the digastric muscle. Ten healthy subjects were
requested to make brisk and self-paced mandibular movements in 4 different
directions (mouth-opening and -closing, and left and right lateral movements). We
obtained MRCPs by averaging the EEG, using the visually determined EMG onset as a
trigger signal. In all the movements, a slowly increasing, bilaterally widespread
negativity starting 1.5 to 2.0 sec before the EMG onset (Bereitschaftspotential,
or BP proper) was observed, with the maximum over the vertex region. The negative
slope (NS') occurred about 300 to 700 msec before the EMG onset. The cortical
maps of BP/NS' (BP and NS' combined), immediately prior to the mouth-opening and
closing, showed a symmetrical distribution, whereas that for the lateral
movements showed a tendency of predominance over the hemisphere ipsilateral to
the direction of the movement. BP/NS' amplitudes at the onset of movement
differed significantly or tended to do so between open, close, and lateral
movements, suggesting that MRCP recordings may thus provide a means to explore
the role of the cerebral cortex in the control of mandibular movements.
PMID- 11005738
TI - Biting and chewing in overdentures, full dentures, and natural dentitions.
AB - It has been suggested that the provision of dental implants can improve the oral
function of subjects with severely resorbed mandibles, possibly restoring
function to the level experienced by satisfied wearers of conventional complete
dentures. Nevertheless, a quantitative comparison has never been made and can be
drawn from the literature only with difficulty, since studies differ greatly in
methodology. To make such a comparison, we measured bite force and chewing
efficiency by using identical methods in subjects with overdentures, complete
full dentures, and natural dentitions. Our results indicated that bite forces
achieved with overdentures on dental implants were between those achieved with
artificial and natural dentitions. Chewing efficiency was significantly greater
than that of subjects with full dentures (low mandible), but was still lower than
that of subjects with full dentures (high mandible) and overdentures on bare
roots. Differences in the height of the mandible revealed significant differences
in chewing efficiency between the two full-denture groups. Furthermore, subjects
with a shortened dental arch exerted bite forces similar to those of subjects
with a complete-natural dentition, but their chewing efficiency was limited due
to the reduced occlusal area. For all groups combined, a significant correlation
was found between maximum bite force and chewing efficiency. Nearly half of the
variation in chewing efficiency was explained by bite force alone.
PMID- 11005739
TI - Effect of food size on the movement of the mandibular first molars and condyles
during deliberate unilateral mastication in humans.
AB - To date, the effect of food size on the movement of the mandibular first molars
and condyles during chewing has not been fully examined due to methodological
problems. The purpose of the present study was to examine the previously unknown
effect of food size on masticatory jaw movement. Using a face bow, light-emitting
diodes, and optical cameras, we recorded, in 16 young adults with good occlusion,
mandibular movement for the first 10 strokes during the unilateral chewing of
similarly shaped hard gummy jellies weighing 5 g and 10 g, respectively. The
chewing cycle time for the 10-g jelly was significantly longer than that for the
5-g jelly. The jaw-closing and -opening maximum velocities, gapes at the maximum
velocities, and maximum gape were significantly faster and larger when 10-g gummy
jellies were chewed, compared with results with 5-g jellies, at the mandibular
first molar on the chewing side and the condyle on the non-chewing side. With the
exception of the velocity, similar tendencies were observed at the molar on the
non-chewing side. However, such significant differences were not detected at the
condyle on the chewing side. The mandibular first molar on the chewing side was
that most affected by food size, and the mean value of the maximum gape coincided
approximately with the height of each jelly. These results suggest that humans
chew hard coherent food such that the mandibular teeth that come into contact
with the food open to a height equivalent to that of the food bolus, and that the
changes in movement of the other parts of the mandible are minimized, ensuring
efficient mastication.
PMID- 11005740
TI - Use of radiology practice guidelines and compliance with accreditation standards
in US and Canadian dental schools.
AB - In 1992 and 1997, all US and Canadian dental schools were surveyed by mail
regarding the preferred initial radiographic examination prescribed for non
emergency, comprehensive-care patients (dentulous adults, edentulous adults, and
children). In both survey years, a minority of US and Canadian dental schools
reported using selection criteria for dentulous adults and children, while nearly
all schools reported doing so for edentulous adults. The purpose of this
secondary analysis was to investigate the relationship between the use of
radiology selection criteria (vs. predetermined routine examinations) in US and
Canadian dental school clinics and three factors: (1) the credentials of the
chief-of-service, (2) institutional funding, and (3) geographic region.
"Credentials of the chief-of-service" is the single factor significantly related
to the distributions of radiographic examinations prescribed for dentulous adults
in both years (Fisher exact test, p < or = 0.02). There are no statistically
significant relationships for edentulous adults or children in either year.
Multivariate analyses (logistic regression) of the 1997 data reveal that
institutions with a credentialed chief-of-service are 2.39 times more likely to
report using selection criteria than institutions with a noncredentialed chief-of
service; private institutions are 1.13 times more likely than public
institutions, and Canadian schools are 3.65 times more likely than US schools. A
similar trend was identified for children. Analysis of the 1992 data revealed
similar trends for the credentials of the chief-of-service and the geographic
region, but showed no association between institutional funding source and the
use of selection criteria. Contrary to accreditation standards, most US and
Canadian dental schools obtained pre-determined routine radiographic examinations
on most new patients. However, the presence of a credentialed chief-of-service
had a positive effect on the use of selection criteria for dentulous adults and
children.
PMID- 11005741
TI - "DentalResearch2000.org".
PMID- 11005742
TI - The Leeds Assessment Scale of Handicap: its operationalisation, reliability,
validity and responsiveness in in-patient rehabilitation.
AB - PURPOSE: This paper describes the application of the handicap dimension of the
International Classification of Impairments, Disabilities and Handicaps. METHOD:
A method of assessing four of the six roles (or areas of expected competency) was
developed and applied to an in-patient population, aged 16 to 65 years, receiving
specialist rehabilitation following neurological damage. Handicap assessment was
a collaborative process by a multidisciplinary team. Difficulties were
experienced in measuring inter-rate reliability in the busy, clinical setting.
RESULTS: We conclude that handicap assessment in an in-patient rehabilitation
unit which uses a multidisciplinary approach to treating patients with complex
physical, sensory and cognitive problems is both feasible and useful. CONCLUSION:
The developed scale, The Leeds Assessment Scale of Handicap, provides a valid and
valuable summary of human disadvantage, complementing the common disability
assessments.
PMID- 11005743
TI - Coping with illness after brain diseases--a comparison between patients with
malignant brain tumors, stroke, Parkinson's disease and traumatic brain injury.
AB - PURPOSE: This study investigates coping styles in patients suffering from
different brain disorders (malignant brain tumors, stroke, Parkinson's disease
and traumatic brain injury). METHOD: In a combined analysis of four prospective
studies we investigated 21 patients with malignant glioma at the end
radiochemotherapy, 30 patients one year after ischemic stroke, 54 patients
suffering from various stages of Parkinson's disease, and 58 patients 6 to 8.5
months after traumatic brain injury. The assessment of coping with illness was
based on the Freiburg Questionnaire on Coping with illness. RESULTS: With few
exceptions, coping styles did not differ across the various brain pathologies.
Differences occurred with respect to 'active, problem-oriented coping' (decreased
in stroke patients), and coping by search for religious relief or quest for sense
(increased in patients with Parkinson's disease). CONCLUSION: Differences in
coping styles could be mainly related to age and social factors. Individual
coping strategies seem only to be little related to the type of brain pathology.
PMID- 11005744
TI - Rehabilitation of stroke patients with apraxia: the role of additional cognitive
and motor impairments.
AB - PURPOSE: The present study investigated which additional cognitive and motor
impairments were present in stroke patients with apraxia and which of these
factors influenced the effects of treatment. METHOD: A group of 33 patients with
apraxia were treated according to the guidelines of a therapy programme based on
teaching patients strategies to compensate for the presence of apraxia. Patients
were treated at occupational therapy departments in general hospitals,
rehabilitation centres and nursing homes. The outcome of the strategy training
was studied in a pre-post test design; measurements were conducted at baseline
and after 12 weeks of therapy. The pretreatment scores of the patients with
apraxia were compared to normscores and scores of a control group of patients
without apraxia (n = 36) to investigate which impairments are present. The
following variables were analysed in order to determine which factors influence
outcome: additional neuropsychological deficits (comprehension of language,
cognitive impairments due to dementia, neglect and short term memory), level of
motor functioning, severity of apraxia and performance on activities of daily
living (ADL), and some relevant patient characteristics (gender, age, type of
stroke, time since stroke, and location of treatment). RESULTS: The results
showed that the presence of apraxia is associated with the presence of additional
cognitive and motor impairments. The successful outcome of strategy training was
not negatively influenced by cognitive comorbidity. The outcome seemed to be more
prominent in patients who were more severely impaired at the start of
rehabilitation in terms of the degree of motor impairments, the severity of
apraxia and the initial ADL dependence. The ADL observations, however, displayed
a ceiling effect, which was taken into account in discussing the results.
Demographic variables, especially age, did not predict the outcome of treatment.
CONCLUSIONS: We suggest that the effect of this training is stronger in more
severely disabled patients. However, neither the presence of additional cognitive
impairments nor the severity of motor problems nor old age should be an
indication for refraining from treating apraxia.
PMID- 11005745
TI - Spiritual issues associated with traumatic-onset disability.
AB - PURPOSE: The present study used a qualitative approach to discover the concepts
used by people with a sudden-onset disability to express issues of spirituality.
Using a cross-sectional time frame, the study sought to understand how spiritual
issues were experienced at the onset of a disability from the perspective of the
disabled person him or herself. The study also compared the perceptions of brain
injury respondents to spinal cord injury respondents. METHOD: The qualitative
approach was chosen to capture a detailed understanding of perceptions about
spirituality, and the relationship of the disability to the disabled person's
spiritual beliefs. The sample consisted of 16 individuals, all of whom had
experienced a spinal cord injury or a brain injury. RESULTS: The main findings of
the study were as follows: (1) Participants recovering from a disability
described spiritual issues relating to five themes which arose directly from the
data (awareness, closeness, trust, purpose, vulnerability) and relating to three
relationships found throughout the literature on spirituality (intrapersonal,
interpersonal and transpersonal). These eight dimensions can be combined to form
a matrix, which serves as a framework for considering spiritual issues associated
with disability; and (2) There were differences in the spiritual concepts
described by the participants with brain injury compared to those with spinal
cord injury. In particular, those with brain injuries seemed to place greater
emphasis on the importance of their families, and to be more aware of the need
for trust in view of their memory deficits. CONCLUSIONS: These results represent
one of the earliest attempts to take an empirical approach to the development of
theory in the area of spirituality and disability. Building on theory developed
in other populations (palliative care and ageing), the study offers a theoretical
model for clinicians, educators and researchers to better understand spirituality
in the context of disability.
PMID- 11005746
TI - Response of prolonged flaccid paralysis to FNS rehabilitation techniques.
AB - PURPOSE: The purpose of this study was to investigate the response of muscles
with prolonged flaccid paralysis (a year after stroke) to two types of treatment:
(1) functional neuromuscular stimulation (FNS) with surface electrodes; and (2)
FNS with intramuscular (IM) electrodes (FNS-IM). A second purpose was to compare
FNS-gait versus volitional gait (no FNS activation). METHOD: We used a single
case study design; our patient was age 72, with flaccid paralysis of knee flexors
and ankle dorsiflexors. RESULTS: Following four months of treatment with surface
stimulation, there was no change in muscle function or gait. Following treatment
with FNS-IM, the patient regained partial volitional control of knee flexors and
dorsiflexors; untreated muscles did not change. CONCLUSION: FNS-gait provided
more normal knee and ankle dorsiflexion during swing phase versus volitional gait
swing phase (no FNS activation).
PMID- 11005747
TI - Severe anaemia: implications for functional recovery during rehabilitation.
AB - PURPOSE: This case report examines the hospital course and functional recovery of
a geriatric patient with severe anaemia undergoing rehabilitation following total
hip replacement. It serves to highlight the need for further study of the impact
of anaemia on recovery in the rehabilitation setting as well as the importance of
developing clinical guidelines for the appropriate medical management of anaemia
in this patient population. METHODS: Single case report. RESULTS: The course of
recovery during rehabilitation in a geriatric patient with severe post-operative
anaemia was notably different from other geriatric patients undergoing
rehabilitation following total hip replacement. The patient demonstrated a
markedly reduced tolerance for therapies and prolonged length of stay, but did
not experience cardiopulmonary complications during intensive rehabilitation. Her
hematocrit responded nicely to treatment with human recombinant erythropoietin.
Despite a prolonged recovery period, the patient ultimately progressed well and
achieved a good functional outcome. CONCLUSIONS: The impact of anaemia on
functional recovery in the acute inpatient rehabilitation setting as well as the
theoretical risk of increased morbidity and mortality during prescribed
therapeutic exercise has not been closely examined in the literature. Further
study is indicated to examine the implications for anaemia on functional recovery
and cardiopulmonary complications during rehabilitation. General guidelines
should be developed for the management of anaemia in the rehabilitation setting.
PMID- 11005748
TI - [Smoking in childhood and adolescence. Role of the pediatrician in control and
prevention].
PMID- 11005749
TI - [Pediatric cardiopulmonary resuscitation equipment in the resuscitation cart or
trolley. Spanish Group of Pediatric and Neonatal Cardiopulmonary Resuscitation].
PMID- 11005750
TI - Fibrogenesis. IV. Fibrosis and inflammatory bowel disease: cellular mediators and
animal models.
AB - The cellular mediators of intestinal fibrosis and the relationship between
fibrosis and normal repair are not understood. Identification of the types of
intestinal mesenchymal cells that produce collagen during normal healing and
fibrosis is vital for elucidating the answers to these questions. Acute injury
may cause normal mesenchymal cells to convert to a fibrogenic phenotype that is
not maintained during normal healing but may lead to fibrosis when
inappropriately sustained. Proliferation of normal or fibrogenic mesenchymal
cells may lead to muscularis overgrowth associated with fibrosis. The presence of
increased numbers of vimentin-positive cells within fibrotic, hypertrophied
muscularis in Crohn's disease suggests that changes in mesenchymal cell phenotype
and number may indeed be associated with fibrosis. Fibrosis is induced in rats by
peptidoglycan polysaccharides or trinitrobenzene sulfonic acid-ethanol
administration, but inducing fibrosis in mice has been technically challenging.
The development of current mouse models of colitis, such as dextran sodium
sulfate or trinitrobenzene sulfonic acid-ethanol administration, into models of
fibrosis will allow us to use genetic manipulation to study molecular mediators
of fibrosis.
PMID- 11005751
TI - Molecular physiology and pathophysiology of tight junctions III. Tight junction
regulation by intracellular messengers: differences in response within and
between epithelia.
AB - Tight junction permeability differs with the type of permeants, their size, and
their charge. Selective changes in permeability do occur, and they illustrate the
diversity in functional reactions of tight junctions. This suggests that special
structures in the tight junctions are involved. More and more structural
components of the tight junctions are becoming known. The divergence in behavior
of native tissue and filter-grown epithelial monolayers with respect to the
effects of intracellular messengers offers the possibility to relate structure
and function. In addition to the tools for conventional permeability studies,
probes have become available to detect changes in activation of intracellular
effector proteins such as the protein kinase C isotypes, and with in situ imaging
techniques the way is open for a functional approach in the study of tight
junctions.
PMID- 11005752
TI - Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil
adhesion to these cells.
AB - Neutrophil infiltration into the pancreas is a key event in pancreatitis. Here we
show that intercellular adhesion molecule-1 (ICAM-1), which regulates neutrophil
adhesion, is present on rat pancreatic acinar cells, is upregulated by a hormone
(cerulein) and mediates direct binding of neutrophils to acinar cells. ICAM-1 was
upregulated in pancreas of rats with experimental pancreatitis induced by
supramaximal doses of cerulein. Furthermore, cerulein time and dose dependently
stimulated expression of ICAM-1 mRNA and protein in isolated pancreatic acinar
cells. Inhibitory analysis showed that activation of transcription factor nuclear
factor-kappaB (NF-kappaB) was involved in ICAM-1 upregulation by cerulein, but NF
kappaB did not mediate basal expression of ICAM-1 mRNA in acinar cells. With an
adhesion assay, we found that neutrophils bind to isolated pancreatic acinar
cells and that cerulein upregulates the extent of adhesion. Neutralizing ICAM-1
antibody blocked neutrophil binding to both control and cerulein-stimulated
acinar cells, suggesting ICAM-1 involvement in this adhesion. Thus the acinar
cell is capable of targeting neutrophils to its surface, a process that may be
important for inflammatory and cell death responses in pancreatitis and other
pancreatic disorders.
PMID- 11005753
TI - Effects of gamma-aminobutyric acid on secretagogue-induced exocrine secretion of
isolated, perfused rat pancreas.
AB - Because GABA and its related enzymes have been determined in beta-cells of
pancreas islets, effects of GABA on pancreatic exocrine secretion were
investigated in the isolated, perfused rat pancreas. GABA, given intra-arterially
at concentrations of 3, 10, 30, and 100 microM, did not exert any influence on
spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However,
GABA further elevated CCK (10 pM)-, gastrin-releasing peptide (100 pM)-, or
electrical field stimulation-induced pancreatic secretions of fluid and amylase
dose dependently. The GABA (30 microM)-enhanced CCK-induced pancreatic secretions
were completely blocked by bicuculline (10 microM), a GABA(A) receptor
antagonist, but were not affected by saclofen (10 microM), a GABA(B) receptor
antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic
secretions were not changed by tetrodotoxin (1 microM) but were partially reduced
by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 nM), a somatostatin
antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by
secretagogues, which predominantly induce enzyme secretion, via GABA(A) receptors
in the rat pancreas. The enhancing effect of GABA is partially mediated by
inhibition of islet somatostatin release.
PMID- 11005754
TI - Endothelin-mediated vasoconstriction in postischemic newborn intestine.
AB - We previously suggested that the profound, sustained vasoconstriction noted in 3
day-old swine intestine after a moderate episode of ischemia-reperfusion (I/R)
reflects the unmasking of underlying constrictor tone consequent to a loss of
endothelium-derived nitric oxide (NO). In this study, we sought to determine
whether endothelin-1 (ET-1) was the unmasked constrictor and whether selective
loss of endothelial ET(B) receptors, which mediate NO-based vasodilation,
participated in the hemodynamic consequences of I/R in newborn intestine. Studies
were performed in innervated, autoperfused intestinal loops in 3- and 35-day-old
swine. Selective blockade of ET(A) receptors with BQ-610 had no effect on
hemodynamics under control conditions; however, when administered before and
during I/R, BQ-610 significantly attenuated the post-I/R vasoconstriction and
reduction in arteriovenous O(2) difference in the younger group. In 3-day-old
intestine, reduction of intestinal O(2) uptake to a level similar to that noted
after I/R by lowering tissue temperature had no effect on the response to BQ-610
or ET-1, indicating that the change in response to BQ-610 noted after I/R was not
simply consequent to the reduction in tissue O(2) demand. In studies in
mesenteric artery rings suspended in myographs, we observed a leftward shift in
the dose-response curve for ET-1 after selective blockade of ET(B) receptors with
BQ-788 in 3- but not 35-day-old swine. Rings exposed to I/R in vivo behaved in a
manner similar to control rings treated with BQ-788 or endothelium-denuded non
I/R rings.
PMID- 11005755
TI - Rectal sensitivity assessed by a reflexologic technique: further evidence for two
types of mechanoreceptors.
AB - We previously showed that slow-ramp rectal distensions induce graded inhibitions
of the somatic nociceptive RIII reflex recorded from the lower limb, which
correlated with both distension volume and visceral sensation. In contrast, rapid
phasic rectal distensions induced facilitatory or biphasic effects (i.e.,
facilitations followed by inhibitions) depending on the level of distension. To
examine the role of mucosal and serosal rectal mechanoreceptors in these
viscerosomatic interactions, we analyzed, in six healthy volunteers, the effects
of both types of rectal distension on the RIII reflex after topical application
of lidocaine or placebo administered in a double-blind and crossover fashion.
Inhibitions of the RIII reflex induced by both slow-ramp and rapid distensions
were strongly reduced after administration of lidocaine but not after placebo. In
contrast, facilitations of the RIII reflex observed during the initial phase of
rapid distensions were not modified after lidocaine or placebo applications.
These results suggest that inhibitions, but not facilitations, of the nociceptive
RIII reflex triggered by rectal distensions depend preferentially on the
activation of superficial mucosal receptors. This reflexologic technique might
thus represent an interesting tool for studying the role of the different rectal
mechanoreceptors involved in visceral sensations.
PMID- 11005756
TI - GH decreases hepatic amino acid degradation after small bowel resection in rats
without enhancing bowel adaptation.
AB - Growth hormone (GH) treatment in short bowel syndrome is controversial, and the
mechanisms of a possible positive effect remain to be elucidated. Rats were
randomly subjected to either an 80% jejunoileal resection or sham operation and
were given either placebo (NaCl) or biosynthetic rat GH (brGH). The in vivo
capacity of urea nitrogen synthesis (CUNS) and the expression of urea cycle
enzymes were measured and related to changes in body weight and adaptive growth
in ileal segments on days 7 and 14. Ileal segments were examined by unbiased
stereological techniques. brGH treatment decreased CUNS among the resected rats
by 19% (P<0.05) and 36% (P<0.05) on days 7 and 14, respectively. The mRNA levels
of urea cycle enzyme genes were not influenced by brGH treatment. brGH treatment
did not increase the adaptive growth in the ileal segments. In conclusion, we
found that GH treatment decreased the accelerated postoperative hepatic amino
acid degradation in experimental short bowel syndrome without enhancing the
morphological intestinal adaptation.
PMID- 11005757
TI - Intestinal ion transport in NKCC1-deficient mice.
AB - The Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) located on the basolateral membrane
of intestinal epithelia has been postulated to be the major basolateral Cl(-)
entry pathway. With targeted mutagenesis, mice deficient in the NKCC1 protein
were generated. The basal short-circuit current did not differ between normal and
NKCC1 -/- jejuna. In the -/- jejuna, the forskolin response (22 microA/cm(2);
bumetanide insensitive) was significantly attenuated compared with the bumetanide
sensitive response (52 microA/cm(2)) in normal tissue. Ion-replacement studies
demonstrated that the forskolin response in the NKCC1 -/- jejuna was HCO(3)(-)
dependent, whereas in the normal jejuna it was independent of the HCO(3)(-)
concentration in the buffer. NKCC1 -/- ceca exhibited a forskolin response that
did not differ significantly from that of normal ceca, but unlike that of normal
ceca, was bumetanide insensitive. Ion-substitution studies suggested that
basolateral HCO(3)(-) as well as Cl(-) entry (via non-NKCC1) paths played a role
in the NKCC1 -/- secretory response. In contrast to cystic fibrosis mice, which
lack both basal and stimulated Cl(-) secretion and exhibit severe intestinal
pathology, the absence of intestinal pathology in NKCC1 -/- mice likely reflects
the ability of the intestine to secrete HCO(3)(-) and Cl(-) by basolateral entry
mechanisms independent of NKCC1.
PMID- 11005758
TI - Effect of galanin and galanin antagonists on peristalsis in esophageal smooth
muscle in the opossum.
AB - Galanin, a neuropeptide that is widely distributed in the esophageal nerves, is
known to exert a neuromodulatory action in the gut. These studies examined the
effect of galanin and galanin antagonists on esophageal peristalsis in
anesthetized opossums in vivo. Intraluminal esophageal pressures were recorded at
1, 3, 5, 7, and 9 cm above the lower esophageal sphincter. Esophageal peristaltic
contractions were induced by swallow and short- (1-s) and long-train (10-s) vagal
stimulation (VS). Galanin (1 nmol/kg) inhibited the amplitude of swallow-induced
peristaltic contractions and increased peristaltic velocity by enlarging the
latency periods in the upper part of the esophagus and reducing them in the lower
part. Galinin nearly abolished esophageal contractions caused by short-train VS
at 5 Hz and inhibited the contractions at 10 Hz. Galanin increased latency
periods induced by short-train VS with little change in the velocity of
peristalsis and reduced the amplitude of both A (cholinergic) and B
(noncholinergic) contractions due to long-train VS. However, the decrease in
amplitude of B contractions was more marked. Galantide (3 nmol/kg) antagonized
the inhibitory action of exogenous galanin on esophageal contractions elicited by
short-train VS, but by itself galantide had no significant effect on esophageal
contractions. In conclusion, exogenous galanin inhibits the amplitude of swallow
induced peristaltic contractions and converts them into nonperistaltic
contractions by inhibiting both the cholinergic and noncholinergic components.
PMID- 11005759
TI - NK-1 receptor desensitization and neutral endopeptidase terminate SP-induced
pancreatic plasma extravasation.
AB - Substance P (SP) induces plasma extravasation and neutrophil infiltration by
activating the neurokinin-1 receptor (NK1-R). We characterized the mechanisms
regulating this response in the rat pancreas. Anesthetized rats were continuously
infused with SP, and plasma extravasation was quantified using Evans blue (EB)
dye. Continuous infusion of SP (8 nmol. kg(-1). h(-1)) resulted in a threshold
increase in EB at 15 min, a peak effect at 30 min (150% increase), and a return
to baseline by 60 min. The NK1-R antagonist CP-96,345 blocked SP-induced plasma
extravasation. After 60 min, the NK1-R was desensitized to agonist challenge.
Resensitization was first detected at 20 min and increased until full recovery
was seen at 30 min. Inhibition of the cell-surface protease neutral endopeptidase
(NEP) by phosphoramidon potentiated the effect of exogenous SP; therefore
endogenous NEP attenuates SP-induced plasma extravasation. Thus the continuous
infusion of SP stimulates plasma extravasation in the rat pancreas via activation
of the NK1-R, and these effects are terminated by both desensitization of the NK1
R and the cell-surface protease NEP.
PMID- 11005760
TI - Identification of gamma-aminobutyric acid receptor subunit types in human and rat
liver.
AB - GABA is a potent inhibitory neurotransmitter that binds to heterooligomeric
receptors in the mammalian brain. In a previous study, we documented specific
GABA binding to isolated rat hepatocytes that resulted in inhibition of
hepatocyte proliferation. The purpose of the present study was to define the
nature of hepatic GABA(A) receptors and to document their expression during rapid
liver growth (after partial hepatectomy). PCRs with gene-specific primers derived
from published sequences were performed with Marathon-ready human and rat liver
cDNA. Two GABA(A) receptor subunit types (beta3 and epsilon) were expressed in
human liver and one subunit type (beta3) in rat liver. PCR amplification of the
human GABA(A) receptorbeta3-subunit produced a single product (molecular mass 53
59 kDa). In the case of the epsilon-subunit, two PCR products were identified.
After partial hepatectomy, GABA(A) receptorbeta3-subunit expression inversely
correlated with regenerative activity (r = -0.527, P = 0.006). In conclusion,
these results indicate that in the human liver GABA(A) receptors consist of the
beta3- and epsilon-subunit types, whereas in the rat liver only the beta3-subunit
type is expressed. The results also support the hypothesis that GABAergic
activity serves to maintain hepatocytes in a quiescent state.
PMID- 11005761
TI - Nitrergic and purinergic regulation of the rat pylorus.
AB - The role of nitric oxide (NO) and ATP in the regulation of nonadrenergic,
noncholinergic (NANC) inhibitory transmission in the pylorus remains unclear. In
the presence of atropine and guanethidine, electric field stimulation induced
NANC relaxations in a frequency-dependent manner (1-20 Hz) in the rat pylorus.
NANC relaxations were significantly inhibited by N(G)-nitro-L-arginine methyl
ester (L-NAME; 10(-4) M). P(2X) purinoceptor antagonist pyridoxal phosphate-6
azophenyl-2',4'-disulfonic acid (PPADS; 3 x 10(-5) M) and P(2Y) purinoceptor
antagonist reactive blue 2 (2 x 10(-5) M) had no effect on NANC relaxations.
However, the combined administration of L-NAME and PPADS, but not reactive blue
2, evoked greater inhibitory effects on NANC relaxation than that evoked by L
NAME alone. alpha-Chymotrypsin and vasoactive intestinal polypeptide antagonist
did not affect NANC relaxations. ATP (10(-5)-10(-3) M) and P(2X) purinoceptor
agonist alpha, beta-methyleneadenosine 5'-triphosphate (10(-7)-10(-5) M), but not
P(2Y) purinoceptor agonist 2-methylthioadenosine 5'-triphosphate (10(-7)-10(-5)
M), induced muscle relaxations in a dose-dependent manner, and relaxations were
significantly reduced by PPADS and unaffected by TTX. These studies suggest that
NO and ATP act in concert to mediate NANC relaxation of the rat pylorus. ATP
induced relaxation appears to be mediated by P(2X) purinoceptors located on
smooth muscle cells.
PMID- 11005762
TI - Cubilin expression and posttranslational modification in the canine
gastrointestinal tract.
AB - Cubilin is an endocytic receptor of the apical brush border membrane that is
essential for intrinsic factor-mediated cobalamin absorption in small intestine.
However, cubilin is more highly expressed in kidney and yolk sac, and recent
molecular characterization of the receptor has focused on these tissues. The aim
of this investigation was to examine tissue-specific cubilin expression and
posttranslational modifications with an emphasis on the gastrointestinal tract.
Intrinsic factor-cobalamin binding activity, cubilin immunoreactivity, and
cubilin mRNA levels were determined in multiple segments of canine
gastrointestinal mucosa and other tissues. These aspects of cubilin expression
varied in parallel, suggesting that the major determinant of regional cubilin
expression in the gastrointestinal tract is modulation of cubilin mRNA. Cell
fractionation indicated that ileal cubilin is not strongly membrane associated.
An approximately 185-kDa brush border specific and two >400-kDa precursor forms
of cubilin were identified. Asparagine-linked oligosaccharide modifications
characterized by differential glycosidase digestion of affinity-purified cubilin
from ileal mucosa and renal cortex differed, but ileal and renal intracellular
cubilin comigrated on SDS-PAGE at approximately 400 kDa after oligosaccharide
removal, thus reconciling previous conflicting size estimates of the cubilin
polypeptide.
PMID- 11005763
TI - Rotavirus alters paracellular permeability and energy metabolism in Caco-2 cells.
AB - Rotaviruses infect epithelial cells of the small intestine, but the
pathophysiology of the resulting severe diarrhea is incompletely understood.
Histological damage to intestinal epithelium is not a consistent feature, and in
vitro studies showed that intestinal cells did not undergo rapid death and lysis
during viral replication. We show that rotavirus infection of Caco-2 cells caused
disruption of tight junctions and loss of transepithelial resistance (TER) in the
absence of cell death. TER declined from 300 to 22 Omega. cm(2) between 8 and 24
h after infection and was accompanied by increased transepithelial permeability
to macromolecules of 478 and 4,000 Da. Distribution of tight junction proteins
claudin-1, occludin, and ZO-1 was significantly altered during infection. Claudin
1 redistribution was notably apparent at the onset of the decline in TER.
Infection was associated with increased production of lactate, decreased
mitochondrial oxygen consumption, and reduced cellular ATP (60% of control at 24
h after infection), conditions known to reduce the integrity of epithelial tight
junctions. In conclusion, these data show that rotavirus infection of Caco-2
intestinal cells altered tight junction structure and function, which may be a
response to metabolic dysfunction.
PMID- 11005765
TI - Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate
transporter 1.
AB - The short-chain fatty acid butyrate was readily taken up by Caco-2 cells.
Transport exhibited saturation kinetics, was enhanced by low extracellular pH,
and was Na(+) independent. Butyrate uptake was unaffected by DIDS; however, alpha
cyano-4-hydroxycinnamate and the butyrate analogs propionate and L-lactate
significantly inhibited uptake. These results suggest that butyrate transport by
Caco-2 cells is mediated by a transporter belonging to the monocarboxylate
transporter family. We identified five isoforms of this transporter, MCT1, MCT3,
MCT4, MCT5, and MCT6, in Caco-2 cells by PCR, and MCT1 was found to be the most
abundant isoform by RNase protection assay. Transient transfection of MCT1, in
the antisense orientation, resulted in significant inhibition of butyrate uptake.
The cells fully recovered from this inhibition by 5 days after transfection. In
conclusion, our data showed that the MCT1 transporter may play a major role in
the transport of butyrate into Caco-2 cells.
PMID- 11005764
TI - Separate pathways for cellular uptake of ferric and ferrous iron.
AB - Separate pathways for transport of nontransferrin ferric and ferrous iron into
tissue cultured cells were demonstrated. Neither the ferric nor ferrous pathway
was shared with either zinc or copper. Manganese shared the ferrous pathway but
had no effect on cellular uptake of ferric iron. We postulate that ferric iron
was transported into cells via beta(3)-integrin and mobilferrin (IMP), whereas
ferrous iron uptake was facilitated by divalent metal transporter-1 (DMT-1; Nramp
2). These conclusions were documented by competitive inhibition studies,
utilization of a beta(3)-integrin antibody that blocked uptake of ferric but not
ferrous iron, development of an anti-DMT-1 antibody that blocked ferrous iron and
manganese uptake but not ferric iron, transfection of DMT-1 DNA into tissue
culture cells that showed enhanced uptake of ferrous iron and manganese but
neither ferric iron nor zinc, hepatic metal concentrations in mk mice showing
decreased iron and manganese but not zinc or copper, and data showing that the
addition of reducing agents to tissue culture media altered iron binding to
proteins of the IMP and DMT-1 pathways. Although these experiments show ferric
and ferrous iron can enter cells via different pathways, they do not indicate
which pathway is dominant in humans.
PMID- 11005766
TI - Systemic lipopolysaccharide influences rectal sensitivity in rats: role of mast
cells, cytokines, and vagus nerve.
AB - Intraperitoneal lipopolysaccharide (LPS) produces somatic hyperalgesia, releases
interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha), and activates
vagal afferents. The aim of this study was to evaluate the effect of peripheral
LPS on rectal sensitivity and to specify the mechanisms involved. Abdominal
muscle contractions were recorded in conscious rats equipped with intramuscular
electrodes. Rectal distension (RD) was performed at various times after LPS or
experimental treatments. In controls, RD significantly increased the number of
abdominal contractions from a threshold volume of distension of 0.8 ml. At the
lowest volume (0.4 ml), this number was increased after administration of LPS (3,
9, and 12 h later), recombinant human IL-1beta (from 3 to 9 h), recombinant
bovine TNF-alpha (from 6 to 9 h), and BrX-537A (from 6 to 12 h), a mast cell
degranulator. The effect of LPS was reduced by doxantrazole, Lys-D-Pro-Thr, and
soluble recombinant TNF receptor. Vagotomy selectively amplified the response to
LPS. We conclude that, in vivo, intraperitoneal LPS lowers visceral pain
threshold (allodynia) through a mechanism involving mast cell degranulation and
IL-1beta and TNF-alpha release and that the vagus nerve may exert a tonic
protective role against LPS-induced rectal allodynia.
PMID- 11005767
TI - Role of cyclooxygenase-2 in Helicobacter pylori- induced gastritis in Mongolian
gerbils.
AB - Cyclooxygenase (COX)-2 expression is induced in the gastric mucosa of
Helicobacter pylori-infected patients, but its role remains unclear. We examined
the effects of NS-398 and indomethacin on gastric pathology in H. pylori-infected
Mongolian gerbils. COX-1 was detected in both normal and H. pylori-infected
mucosa, whereas COX-2 was expressed only in the infected mucosa. PGE(2)
production was elevated by H. pylori infection, and the increased production was
reduced by NS-398, which did not affect PGE(2) production in normal mucosa.
Indomethacin inhibited PGE(2) production in both normal and infected mucosa.
Hemorrhagic erosions, neutrophil infiltration, lymphoid follicles, and epithelium
damage were induced by H. pylori infection. NS-398 and indomethacin aggravated
these pathological changes but did not increase viable H. pylori number. H.
pylori-increased production of neutrophil chemokine and interferon-gamma was
potentiated by NS-398 and indomethacin. Neither NS-398 nor indomethacin caused
any pathological changes or cytokine production in normal animals. These results
indicate that COX-2 as well as COX-1 might play anti-inflammatory roles in H.
pylori-induced gastritis.
PMID- 11005768
TI - Transport of procainamide via H(+)/tertiary amine antiport system in rabbit
intestinal brush-border membrane.
AB - Transport characteristics of procainamide in the brush-border membrane isolated
from rabbit small intestine were studied by a rapid-filtration technique.
Procainamide uptake by brush-border membrane vesicles was stimulated by an
outward H(+) gradient (pH(in) = 6.0, pH(out) = 7.5) against a concentration
gradient (overshoot phenomenon), and this stimulation was reduced when the H(+)
gradient was subjected to rapid dissipation by the presence of a protonophore,
FCCP. An outward H(+) gradient-dependent procainamide uptake was not caused by
H(+) diffusion potential. The initial uptake of procainamide was inhibited by
other tertiary amines with N-dimethyl or N-diethyl moieties in their structures,
such as triethylamine, dimethylaminoethyl chloride, and diphenhydramine, but not
by tetraethylammonium and thiamine. Furthermore, procainamide uptake was
stimulated by preloading the vesicles with these tertiary amines (trans
stimulation effect), indicating the existence of a specific transport system for
tertiary amines. These findings indicate that procainamide transport in the
intestinal brush-border membrane is mediated by the H(+)/tertiary amine antiport
system that recognizes N-dimethyl or N-diethyl moieties in the structures of
tertiary amines.
PMID- 11005769
TI - Role of gut-enriched Kruppel-like factor in colonic cell growth and
differentiation.
AB - Cancer cells differ from normal cells in many aspects, including
hyperproliferation and loss of differentiation. Recent research has focused on
the role of transcription factors in regulating abnormal cell growth. Gut
enriched Kruppel-like factor (GKLF) is a newly identified eukaryotic zinc finger
protein expressed extensively in the gastrointestinal tract. In the current
study, we demonstrated that GKLF mRNA levels were significantly decreased in the
dysplastic epithelium of the colon, including adenomatous polyp and cancer. GKLF
immunostains in the normal colon were higher at the surface epithelium and
gradually decreased toward the crypt, but this gradient was not present in the
adenomatous and cancerous mucosa. Constitutive overexpression of GKLF DNA in a
human colonic adenocarcinoma cell line (HT-29) decreased [(3)H]thymidine
incorporation, whereas suppression of GKLF gene increased DNA synthesis,
indicating that downregulation of the GKLF gene might contribute to cellular
hyperproliferation. Cyclin D1 (CD1) protein level and CD1-associated kinase
activity were decreased in HT-29 cell overexpressed GKLF cDNA, and CD1 promoter
activity was profoundly suppressed by GKLF. When HT-29 cells were cultured in the
presence of sodium butyrate, GKLF mRNA levels increased as cells acquired more
differentiated phenotypes. These results suggest that GKLF plays an important
role in regulating cell growth and differentiation in the colonic epithelium and
that downregulation of GKLF expression may cause colonic cells to become
hyperproliferative. Furthermore, GKLF appears to be a transcriptional repressor
of the CD1 gene.
PMID- 11005770
TI - Cell transplantation causes loss of gap junctions and activates GGT expression
permanently in host liver.
AB - Cell transplantation into hepatic sinusoids, which is necessary for liver
repopulation, could cause hepatic ischemia. To examine the effects of cell
transplantation on host hepatocytes, we transplanted Fisher 344 rat hepatocytes
into syngeneic dipeptidyl peptidase IV-deficient rats. Within 24 h of cell
transplantation, areas of ischemic necrosis, along with transient disruption of
gap junctions, appeared in the liver. Moreover, host hepatocytes expressed gamma
glutamyl transpeptidase (GGT) extensively, which was observed even 2 years after
cell transplantation. GGT expression was not associated with alpha-fetoprotein
activation, which is present in progenitor cells. Increased GGT expression was
apparent after transplantation of nonparenchymal cells and latex beads but not
after injection of saline, fragmented hepatocytes, hepatocyte growth factor, or
turpentine. Some host hepatocytes exhibited apoptosis, as well as DNA synthesis,
between 24 and 48 h after cell transplantation. Changes in gap junctions, GGT
expression, DNA synthesis, and apoptosis after cell transplantation were
prevented by vasodilators. The findings indicated the onset of ischemic liver
injury after cell transplantation. These hepatic perturbations must be considered
when transplanted cells are utilized as reporters for biological studies.
PMID- 11005771
TI - p53-dependent acinar cell apoptosis triggers epithelial proliferation in duct
ligated murine pancreas.
AB - The mechanisms linking acinar cell apoptosis and ductal epithelial proliferation
remain unknown. To determine the relationship between these events, pancreatic
duct ligation (PDL) was performed on p53(+/+) and p53(-/-) mice. In mice bearing
a wild-type p53 allele, PDL resulted in upregulation of p53 protein in both
acinar cells and proliferating duct-like epithelium. In contrast, upregulation of
Bcl-2 occurred only in duct-like epithelium. Both p21(WAF1/CIP1) and Bax were
also upregulated in duct-ligated lobes. After PDL in p53(+/+) mice, acinar cells
underwent widespread apoptosis, while duct-like epithelium underwent
proliferative expansion. In the absence of p53, upregulation of p53 target genes
and acinar cell apoptosis did not occur. The absence of acinar cell apoptosis in
p53(-/-) mice also eliminated the proliferative response to duct ligation. These
data demonstrate that PDL-induced acinar cell apoptosis is a p53-dependent event
and suggest a direct link between acinar cell apoptosis and proliferation of duct
like epithelium in duct-ligated pancreas.
PMID- 11005772
TI - Evaluation of multiple-point measurement of sphincter of Oddi motility in the
Australian brush-tailed possum.
AB - Manometric assembly diameter is a major limitation on the number of perfused
manometric recording points for recordings from the sphincter of Oddi (SO). We
evaluated novel polyimide manometric assemblies whereby four recording channels
were incorporated in an overall assembly diameter of 0.8 mm. Over the very low
range of perfusion rates tested (0.005-0.04 ml/min), the assemblies had pressure
offsets attributable to water perfusion from 2 to 23 mmHg and pressure rise rates
from 20 to 163 mmHg/s. In six anesthetized Australian brush-tailed possums,
manometric recordings from the SO showed a significant reduction in the recorded
peak amplitude of pressure waves with perfusion rates below 0.02 ml/min. The
pressure profile of the sphincter was found to be asymmetric, and phasic wave
propagation patterns were complex (antegrade 35.6%, "mixed" 64.4%). In
conclusion, accurate multipoint SO manometry in the possum can be performed with
micromanometric assemblies at very low perfusion rates to give a more complete
understanding of SO mechanics. These methods are also potentially applicable to
perfusion manometry in other small laboratory animals such as mice.
PMID- 11005773
TI - Systematic review of the cost effectiveness of prophylactic treatments in the
prevention of gastropathy in patients with rheumatoid arthritis or osteoarthritis
taking non-steroidal anti-inflammatory drugs.
AB - A systematic review on the cost effectiveness of prophylactic treatments of non
steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with
osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the
literature search and the review. Both full and partial economic evaluations
published in English, Dutch, or German were included. The criteria list published
in the textbook of Drummond was used to determine the quality of the economic
evaluations. The methodological quality of three randomised controlled trials
(RCTs) in which the economic evaluations obtained probability estimates of NSAID
induced gastropathy and adverse events was assessed by a list of internal
validity criteria. The conclusions were based on a rating system consisting of
four levels of evidence. Ten economic evaluations were included; three were based
on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one
evaluation misoprostol was studied as a fixed component in a combination with
diclofenac (Arthrotec). All economic evaluations comprised analytical studies
containing a decision tree. The three trials were of high methodological quality.
Nine economic evaluations were considered high quality and one economic
evaluation was considered of low methodological quality. There is strong evidence
(level "A") that the use of misoprostol for the prevention of NSAID induced
gastropathy is cost effective, and limited evidence (level "C") that the use of
Arthrotec is cost effective. Although the levels of evidence used in this review
are arbitrary, it is believed that a qualitative analysis is useful: quantitative
analyses in this field are hampered by the heterogeneity of economic evaluations.
Existing criteria to evaluate the methodological quality of economic evaluations
may need refinement for use in systematic reviews.
PMID- 11005774
TI - Teaching the teachers: ways of improving teaching and identifying areas for
development.
PMID- 11005776
TI - Standing committee on epidemiology and health services research: past, present,
and future
PMID- 11005777
TI - Monocyte chemoattractant protein 1 (MCP-1) in temporal arteritis and polymyalgia
rheumatica.
AB - OBJECTIVE: To examine the localisation of monocyte chemoattractant protein 1 (MCP
1) in the inflamed vessel wall in temporal arteritis (TA) and to measure MCP-1 in
plasma both in patients with TA and patients with polymyalgia rheumatica (PMR).
METHODS: By immunohistochemical techniques MCP-1 was localised to the vessel wall
in patients with TA. In TA, PMR, and healthy controls MCP-1 was quantified by
enzyme linked immunosorbent assay (ELISA) in plasma. RESULTS: MCP-1 was localised
to the majority of mononuclear cells, some smooth muscle cells, and giant cells
in the arterial biopsy specimens from 12 patients with histologically verified
TA. In all sections, including the vasa vasorum, the endothelium stained
positive. In the intima 73% (range 57-91%), in the media 49% (range 32-67%), and
in the adventitia 74% (range of 62-91%) of all cells stained positive. In plasma
MCP-1 was significantly raised in untreated TA (n=33) and untreated PMR (n=27)
compared with healthy controls (n=12). Untreated TA plasma levels of MCP-1 (mean
391 pg/ml (range 82-778 pg/ml)) were similar to untreated PMR plasma levels (mean
402 pg/ml (range 29-1153 pg/ml)), and no significant difference was found between
the two groups of patients. In both patients with TA and patients with PMR no
correlation was found between the plasma level of MCP-1 and the erythrocyte
sedimentation rate, haemoglobin concentration, and CD4/CD8 ratio. CONCLUSIONS:
These results show that MCP-1 plays a part in the disease processes of TA and
PMR.
PMID- 11005775
TI - Background for studies on the treatment of male osteoporosis: state of the art.
AB - Male osteoporosis represents an important, although long underestimated, public
health problem. Both in men and in women aging is accompanied by continuous bone
loss and by an exponential increase in the incidence of osteoporotic fracture,
with a female to male incidence ratio of about 2 to 3 to 1 in the elderly for hip
and vertebral fractures. Morbidity after osteoporotic fractures appears to be
more serious and mortality more common in men than in women. To date, no single
treatment has been proved to be effective and safe in published prospective
studies. The present report, based on a systematic search of the literature on
male osteoporosis, summarises the state of the art on the clinical consequences
of male osteoporosis and its risk factors, in relation to the present state of
knowledge about female osteoporosis. This constitutes the background for the
design of rational clinical development strategies for therapeutic interventions
in male osteoporosis. From this review of the literature it is apparent that
notwithstanding the existing sex differences in pathophysiology of osteoporosis
and the difference in age-specific incidence of osteoporotic fractures, there are
also important similarities between osteoporosis in women and men. The higher
incidence of fracture in women than in men results from quantitative differences
in risk factors rather than from different risk factors. Even though there are
sex differences in bone geometry, incidence of fracture seems to be similar in
men and women for a same absolute areal bone mineral density. However, the lack
of data on the changes in fracture rates in men resulting from pharmacological
intervention, leading to changes in bone mineral density or bone turnover,
remains the main limitation for extrapolation of established treatment outcomes
from women to men.
PMID- 11005778
TI - Effect of thrombin inhibition on synovial inflammation in antigen induced
arthritis.
AB - OBJECTIVE: To determine the effect of the thrombin inhibitor, hirudin, on the
pathogenesis of murine antigen induced arthritis (AIA). METHODS: AIA was induced
by intra-articular injection of methylated bovine serum albumin in the knee
joints of previously immunised mice. Hirudin (injected subcutaneously 3 x 200
microg/mouse/day) was given over 13 days, starting three days before arthritis
onset, and its anticoagulant effect monitored by clotting times. Arthritis
severity was evaluated by technetium-99m ((99m)Tc) uptake in the knee joints and
by histological scoring. In addition, intra-articular fibrin deposition was
examined by immunohistochemistry, and synovial cytokine mRNA expression measured
by RNase protection. RESULTS: Joint inflammation, measured by (99m)Tc uptake, was
significantly reduced in hirudin treated mice at days 7 and 10 after arthritis
onset. Histologically, synovial thickness was markedly decreased in hirudin
treated mice compared with untreated ones. By contrast, no difference in
articular cartilage proteoglycan content was found between both groups. Intra
articular fibrin deposition and synovial interleukin 1beta mRNA levels, were
slightly reduced ( approximately 20%) in arthritic joints from hirudin treated
mice compared with untreated ones at day 10 of AIA. CONCLUSION: Hirudin reduces
joint inflammation associated with AIA by fibrin-dependent and independent
mechanisms.
PMID- 11005779
TI - A population study of factors associated with general practitioner consultation
for non-inflammatory musculoskeletal pain.
AB - OBJECTIVE: To investigate factors associated with visiting a general practitioner
(GP) for non-inflammatory musculoskeletal pain, and to examine whether these
factors were affected by duration (chronic v non-chronic) or location (widespread
v regional) of pain. METHODS: From a cross sectional postal survey of 20 000
(response rate 59%) randomly selected adults in two counties of Norway, 6408
subjects who had experienced musculoskeletal pain during the past month were
included. Patients who reported inflammatory rheumatic diagnoses made by a doctor
were excluded. RESULTS: 2909 (45%) had consulted a GP for their musculoskeletal
pain during the past 12 months. The odds of consulting were significantly
increased by being a woman, by having a higher age and lower education, and by
being a pensioner or on sick leave. Patients with widespread pain were more
likely to consult than those with regional pain, as were patients with chronic
compared with non-chronic pain. Greater than median pain intensity was the factor
most prominently associated with consultation for men (odds ratio (OR)=2.4; 95%
confidence interval (95% CI) 2.0 to 2.9) and for women (OR=2.6; 95% CI 2.3 to
2.9). Overall, consultation was significantly associated with mental distress for
women but not for men. Subgroup analyses showed that consultation for chronic
pain was significantly associated with greater than median mental distress for
both women (OR=1.3; 95% CI 1.1 to 1.6) and men (OR=1.2; 95% CI 1. 0 to 1.4),
whereas consultation for non-chronic pain was not. CONCLUSION: The results show
that about half of the patients with musculoskeletal pain consult a general
practitioner (GP) each year, that demographic factors are associated with
consulting, and that the role of mental distress for consulting a GP varies with
duration of pain.
PMID- 11005781
TI - Pregnancy in patients with Wegener's granulomatosis: report of five cases in
three women.
AB - Five cases of pregnancy occurring in three women with previously diagnosed
Wegener's granulomatosis are described. The disease was diffuse in one case and
localised in the other. Initial treatment consisted of a combination of
corticosteroids and intravenous cyclophosphamide in two women, and methotrexate
in one. Four pregnancies ended in live births despite pre-eclampsia in two cases.
One therapeutic abortion was induced because of encephalocele. Comparable
reported cases were reviewed to examine the implications of immunosuppressive
treatment on the fetus. A relapse occurred during pregnancy in 40% of the cases,
but in 25% if only pregnancies beginning during inactive disease were taken into
account. No other indicator for maternal and fetal outcome was obvious. Pregnancy
should be planned after complete disappearance of disease activity. In the case
of a relapse a combination of immunosuppressive drugs and corticosteroids should
be chosen rather than corticosteroids alone because the outcome of pregnancy is
poor in cases of undertreatment. Prematurity remains common.
PMID- 11005780
TI - Socioeconomic deprivation and rheumatoid disease: what lessons for the health
service? ERAS Study Group. Early Rheumatoid Arthritis Study.
AB - OBJECTIVE: To assess how socioeconomic deprivation influences the presentation,
treatment, and outcome of patients with rheumatoid arthritis (RA). METHODS: Three
year follow up of 869 consecutive patients with RA from nine hospital
rheumatology clinics, with patients categorised by the Carstairs deprivation
score of their enumeration district of residence. Outcomes included Health
Assessment Questionnaire (HAQ), joint and pain scores, grip strength, functional
grade, radiological evidence of bony erosions, and medical/surgical
interventions. RESULTS: Patients from more deprived enumeration districts
presented with more severe disease as judged by the HAQ score and joint scores.
An increase from the 5th to the 95th centile of the Carstairs distribution was
associated with an odds ratio of 1.87 (95% confidence interval (95% CI) 1.31 to
2.66) for an above-median HAQ score and 1.77 (95% CI 1.23 to 2.54) for an above
median joint score. Statistically non-significant deprivation trends were seen
with erythrocyte sedimentation rate, pain score, and grip strength. By three
years, despite no important differences in clinical management, socioeconomic
differentials had worsened or remained unchanged such that clear deprivation
trends were then seen in HAQ (p=0.002) and joint scores (p=0.001), in grip
strength (p=0. 008), and in functional grade (p=0.003). The association between
deprivation and HAQ at three years was present after adjustment for age, sex,
treatment centre, and HAQ at presentation (adjusted odds ratio 1.74, 95% CI 1.1
to 2.74). CONCLUSIONS: Socioeconomic deprivation was associated with a worse
clinical course of rheumatoid disease, and this effect was already apparent at
presentation, but not with systematic differentials in its treatment. This
suggests that individual susceptibility and lifestyle factors contribute to
socioeconomic differentials in outcome, an observation that has implications for
clinical management.
PMID- 11005782
TI - Data driven attempt to create a clinical algorithm for identification of women
with rheumatoid arthritis at high risk of osteoporosis.
AB - OBJECTIVES: To examine relations between osteoporosis and low bone mass and
demographic and clinical variables in patients with rheumatoid arthritis (RA), in
an attempt to develop a data driven clinical tool for identification of patients
at high risk of osteoporosis. METHODS: All patients were recruited from a county
based register and were examined cross sectionally with a variety of clinical and
health status measures as well as bone density measures (anteroposterior spine L2
4, total hip, and femoral neck). Associations between osteoporosis (T score < or
= -2.5SD) and low bone mass (T score < or = -1SD), on the one hand, and
demographic and clinical measures, on the other, were examined bivariately and by
logistic regression analyses. RESULTS: 394 patients with a mean age of 54.8 years
were examined. The percentages having osteoporosis/low bone mass were 16.8/45.8,
14.7/54.5 and 14.7/55.5 in spine L2-4, total hip, and femoral neck, respectively.
Osteoporosis and low bone mass were bivariately related to age, body mass index
(BMI), disease duration, disease process measures, presence of deformed joints,
physical disability, current use of corticosteroids, and history of non-vertebral
fracture. In multivariate analyses, age >60 years, low BMI, and current use of
corticosteroids were consistently related to osteoporosis and to low bone mass at
all sites. The presence of deformed joints was associated with osteoporosis at
the total hip, and a history of previous non-vertebral fracture with osteoporosis
at the femoral neck. The Modified Health Assessment Questionnaire (MHAQ) > or =
1.5 and non-vertebral fracture were also independently associated with low bone
mass at the hip. The logistic regression analyses models could, however, only
predict osteoporosis with a sensitivity of about 50-60% and a specificity of 80
90% at the various measurement sites, and low bone mass with a sensitivity and
specificity of about 70%. CONCLUSION: Consideration of demographic and disease
markers may be of some help in predicting presence of osteoporosis or low bone
mass, but a combination of markers cannot be used as a clinical tool with
sufficient sensitivity and specificity for the identification of osteoporosis or
low bone mass in patients with RA.
PMID- 11005783
TI - Motor performance of the hand in patients with rheumatoid arthritis.
AB - OBJECTIVES: To examine the motor performance of the hand in a sample of patients
with rheumatoid arthritis (RA). SUBJECTS: The patient group comprised 21 (two
men, 19 women) patients with RA. Twenty one control subjects matched for age and
sex were selected from a larger reference group, which had been drawn from the
local population. METHODS: The measured motor performance aspects were simple
reaction time, choice reaction time, speed of movement, finger tapping speed, and
coordination (that is, speed of movement/accuracy). Results were compared for age
and sex matched pairs. The measurements were made with the Human Performance
Measurement/Basic Elements of Performance system, which is a multifunctional
system designed to measure different motor aspects of the hands, including
reaction time, movement speed, tapping speed, and coordination. RESULTS: A
comparison of the results for the patient and control groups indicated that the
motor functions of patients with RA were impaired in all the measured aspects
(with the exception of the index finger tapping test). The difference between the
groups varied between 11% and 21% for the reaction time tasks, between 12% and
18% for the speed of movement tasks, and between 15% and 17% for the coordination
task. CONCLUSION: Based on the results of our research, it seems that RA
decreases some motor performance functions of the hand expressed as simple
reaction time, choice reaction time, speed of movement, and coordination. The
changes were emphasised in movements performed with several joints.
PMID- 11005784
TI - Bilateral hip osteonecrosis: influence of hip size on outcome.
AB - OBJECTIVE: To measure the volume of osteonecrosis in 30 patients with disease in
both hips (one side with collapse and the other without at Ficat stage I).
METHOD: The volume of the osteonecrosis was measured by magnetic resonance
imaging. RESULTS: The progression to collapse was influenced by the size of the
lesion in each patient. The first collapsed hip was that with the largest volume
of osteonecrosis. CONCLUSION: The volume of the osteonecrotic lesion on the
second hip (stage I without collapse) is a good predictor of the time to collapse
of this second hip.
PMID- 11005785
TI - Expression of epidermal growth factor and transforming growth factor alpha in
interfacial membranes retrieved at revision total hip arthroplasty.
AB - BACKGROUND: The interfacial membrane between bone and implant has been shown to
be a key tissue in the process of aseptic loosening of total hip arthroplasty.
The cells within the interfacial membrane produce numerous inflammatory mediators
which, through complex mechanisms, cause periprosthetic osteolysis and aseptic
loosening. Both epidermal growth factor (EGF) and transforming growth factor
alpha (TGFalpha) have similar biological functions. They have been found to
stimulate bone resorption. OBJECTIVE: To investigate the presence, cellular
localisation, and extent of expression of EGF and TGFalpha in interfacial
membrane retrieved from revision total hip arthroplasty and compare it with that
in synovial membrane from primary total hip arthroplasty. METHODS: Ten
interfacial membranes and 10 synovial membranes were stained with avidin-biotin
peroxidase complex for EGF and TGFalpha. The staining process was done using the
Lab Vision Autostainer. The results were measured by a semiautomatic VIDAS image
analysis system. RESULTS: Immunoreactivity for both EGF and TGFalpha was found in
the endothelial cells of blood vessels, macrophages, and fibroblasts, both in
interfacial membranes and synovial membranes. However, the number of EGF (980
(370)) and TGFalpha (1070 (360)) positive cells per mm(2) was greater in
interfacial membranes than in the synovial membranes (220 (200), 270 (100);
p<0.01). CONCLUSION: It is suggested that owing to their increased expression in
interfacial membrane, EGF and TGFalpha may have an important pathogenetic role in
stimulating periprosthetic bone resorption in aseptic loosening of total hip
arthroplasty.
PMID- 11005786
TI - Serum levels of YKL-40 and C reactive protein in patients with hip osteoarthritis
and healthy subjects: a cross sectional study.
AB - BACKGROUND: YKL-40 is a 40 kDa glycoprotein secreted by chondrocytes and
synoviocytes. It has been suggested that it is a surrogate marker of synovial
inflammation and joint destruction in rheumatoid arthritis (RA) and
osteoarthritis (OA) and related to C reactive protein (CRP) serum levels in RA.
OBJECTIVE: To study serum levels of YKL-40 in patients with hip OA and its
relation with CRP. METHODS: YKL-40 and CRP were assayed in serum samples from 45
patients (24 women, 21 men, mean age 65) with symptomatic OA of the hip and 33
healthy controls. YKL-40 was assayed by immunoassay and CRP by ultrasensitive
immunonephelometry. OA severity was assessed by the measurement of joint space
width with a computer analysis system of digitised hip radiographs. Statistical
analysis was performed to determine correlations between serum markers and
radiological joint space width. RESULTS: The mean (standard error) YKL-40 level
was 90.3 (8.2) ng/ml in patients with hip OA and 66.9 (8.2) ng/ml in controls
(p=0.03). The mean CRP level was 2.93 (3.03) mg/l in OA and 1.40 (1.61) mg/l in
controls (p=0.006). The serum levels of YKL-40 and CRP increased with age and
were significantly correlated (Spearman test: r(s)=0.42, p=0.005) in patients but
not in controls. Neither YKL-40 nor CRP correlated with radiographic joint space
width. CONCLUSIONS: Serum YKL-40 was significantly increased in patients with hip
OA. The correlation between YKL-40 and CRP suggests that YKL-40 may be a marker
of joint inflammation in OA. Longitudinal studies are required to assess the
usefulness of YKL-40 in the monitoring of patients with hip OA.
PMID- 11005787
TI - Do present damage and health perception in patients with systemic lupus
erythematosus predict extent of future damage?: a prospective study.
AB - OBJECTIVE: To study whether either initial damage, disease activity, disease
duration, age, a drug score, or health status would predict an increase in damage
in patients with systemic lupus erythematosus (SLE) within the next three years.
METHODS: A three year prospective longitudinal study of a cohort of 141
consecutive patients with SLE attending a specialist lupus outpatient clinic from
their first assessment between July 1994 and February 1995. Disease activity was
assessed using the BILAG system, health status by the Medical Outcome Survey
Short Form 20 with an extra question about fatigue (SF-20+), and damage by the
SLICC/ACR Damage Index (SDI). Damage was reassessed three years later.
Statistical analysis was carried out using logistic regression analysis
(logXact). RESULTS: 133 female and 8 male patients with SLE (97 white subjects,
16 Afro-Caribbeans, 22 Asians, and 6 others) were included. Their mean (SD) age
at inclusion was 41.1 (12.5) years and their disease duration 10.2 (6. 3) years.
The mean measures at inclusion were: total BILAG 5.2 (range 0-17), total SDI 1.2
(0-7), drug score 1.2 (0-3); SF-20+: physical 58 (0-100), role 54 (0-100), social
functioning 71 (0-100), mental health 64 (16-100), health perception 44 (0-100),
pain 53 (0-100), fatigue 59 (0-100). Four patients were lost to follow up because
they had moved. At three years in 33 patients the total SDI had increased to a
mean of 1.5 (0-7) (n=130). Moreover, seven patients had the maximum damage as
they had died during the follow up period. The only variables with an independent
and significant contribution in predicting damage at three years were the total
damage score (odds ratio (OR)=1.46; 95% CI 1.04 to 2.05), and health perception
(OR=0.96; 95% CI 0.93 to 0.99) at inclusion. CONCLUSIONS: Of all the variables at
inclusion only the total damage score and SF-20+: health perception,
significantly predicted an increase in damage, for patients with SLE, three years
later.
PMID- 11005788
TI - Unusual presentation of familial Mediterranean fever: role of genetic diagnosis.
AB - OBJECTIVE: To describe the role of molecular analysis in the diagnosis of an
unusual presentation of familial Mediterranean fever (FMF). CASE REPORT: Two
patients presenting with prolonged fever without signs and symptoms of serositis
are described. FMF was diagnosed by genetic analysis, which disclosed that both
patients were homozygous for the M694V mutation of the Mediterranean fever (MEFV)
gene. CONCLUSION: Molecular analysis of FMF should complement the investigation
of patients with fever of unknown origin. This test enables a definite diagnosis
of the disease and may promote the diagnosis and treatment of patients with an
unusual or incomplete clinical picture of FMF.
PMID- 11005789
TI - Decoding the human genome sequence.
AB - The year 2000 is marked by the production of the sequence of the human genome. A
'working draft' of high quality sequence covering 90% of the genome has been
determined and a quarter is in finished form, including the first two completed
chromosomes. All sequence data from the project is made freely available to the
community via the Internet, for further analysis and exploitation. The challenge
which lies ahead is to decipher the information. Knowledge of the human genome
sequence will enable us to understand how the genetic information determines the
development, structure and function of the human body. We will be able to explore
how variations within our DNA sequence cause disease, how they affect our
interaction with our environment and ultimately to develop new and effective ways
to improve human health.
PMID- 11005790
TI - Genetics of asthma and allergic disease.
AB - Atopic (allergic) asthma is the most common disease of childhood and is strongly
genetic in origin. Many genome-wide screens for asthma and its associated traits
have now been carried out, and genetic linkage has been consistently identified
in several regions. It is probable that these loci contain major genes
influencing atopy and asthma. Candidate genes have already been identified from
the cytokine cluster on chromosome 5 and the MHC on chromosome 6. These complex
regions contain more than one susceptibility locus for allergic disease. Other
regions do not contain obvious candidate genes, and positional cloning of these
loci is likely to identify novel disease pathways. Parent-of-origin effects are
prominent at some of the loci and some also show linkage to other inflammatory
immune diseases. Several single gene disorders are associated with allergic
disease and on occasion are also linked to the same chromosomal regions. The
positional cloning of asthma genes is now feasible.
PMID- 11005791
TI - Rett syndrome: a surprising result of mutation in MECP2.
AB - The identification of mutations in the gene encoding methyl CpG binding protein 2
(MeCP2) in Rett syndrome represents a major advance in the field. The current
model predicts that MeCP2 represses transcription by binding methylated CpG
residues and mediating chromatin remodeling. A physical interaction between
MeCP2, histone deacetylases and the transcriptional co-repressor Sin3A has been
demonstrated, as well as an association of MeCP2 with the basal transcription
apparatus. It is unclear, however, whether MeCP2-mediated chromatin remodeling is
necessary for transcriptional repression in vivo. Eight recurrent missense and
nonsense mutations account for >65% of the mutations identified in Rett syndrome
probands, and as predicted from the sporadic nature of the disorder, most
mutations are de novo. The severity of the phenotype is likely to reflect the
pattern of X chromosome inactivation in relevant tissues, although the type and
position of the mutation may also play a role. Although much is known about the
biochemical function of MeCP2, the phenotype of Rett syndrome suggests that it
plays an unexplored but critical role in development and maintenance of the
nervous system.
PMID- 11005792
TI - Haemochromatosis: novel gene discovery and the molecular pathophysiology of iron
metabolism.
AB - The application of molecular genetics to haemochromatosis and experimental
mutagenesis in animals has transformed our capacity to investigate the unique
physiology of iron homeostasis-a key problem in biology and medicine. The
identification of HFE, the principal determinant of adult haemochromatosis (HFE1;
OMIM 235200) and TfR2, recently implicated in a rarer form of the inherited
disorder (HFE3; OMIM 604250), and the promise of candidate genes for juvenile
haemochromatosis (HFE2; OMIM 602390) and neonatal haemochromatosis (OMIM 231100)
provide the foundation for important studies into the control mechanism of iron
balance in humans. The rare conditions atransferrinaemia (OMIM 209300) and
acaeruloplasminaemia (OMIM 604290), each associated with tissue iron overload,
have already implicated the iron transport ligand transferrin and the copper
transporter caeruloplasmin in the control of iron homeostasis. Gene mapping
studies in animal mutants with anaemia due to defects in the uptake or tissue
transfer of iron have yielded novel proteins involved in iron transport: DMT1
(brush border transporter of ferrous iron) in the mk/mk mouse, hephaestin
(basolateral multi-copper ferroxidase) in the sex-linked anaemic mouse (sla) and
ferroportin1 (basolateral iron exporter) in zebrafish weh mutants. The discovery
of genes that determine heritable defects of iron absorption and regulation in
animals and humans thus holds promise for a complete mechanistic understanding of
the molecular pathophysiology of iron metabolism.
PMID- 11005793
TI - Transcriptional regulation of Alzheimer's disease genes: implications for
susceptibility.
AB - In recent years, important progress has been made in uncovering genes implicated
in Alzheimer's disease (AD). Three causal genes have been identified in which
mutations cause familial presenile AD: the amyloid precursor protein gene and the
presenilin 1 and 2 genes. Additionally, the epsilon 4 allele of the
apolipoprotein E gene was shown to be a major risk factor for AD. Despite the
genetic heterogeneity, all of these genes work through a common mechanism, i. e.
increasing the amount and deposition of the amyloid beta peptide (A beta) in
brain triggering AD-related neuronal degeneration. Therefore, the levels of A
beta and of the factors involved in its production and deposition are important
in the neuropathogenesis of AD. Regulation of transcription of AD genes might
therefore be an important player in the neurodegenerative process. In this
review, we describe the major features of transcriptional regulation of the known
AD genes and the implications of variable expression levels on susceptibility to
AD.
PMID- 11005794
TI - The DNA methyltransferases of mammals.
AB - The biological significance of 5-methylcytosine was in doubt for many years, but
is no longer. Through targeted mutagenesis in mice it has been learnt that every
protein shown by biochemical tests to be involved in the establishment,
maintenance or interpretation of genomic methylation patterns is encoded by an
essential gene. A human genetic disorder (ICF syndrome) has recently been shown
to be caused by mutations in the DNA methyltransferase 3B (DNMT3B) gene. A second
human disorder (Rett syndrome) has been found to result from mutations in the
MECP2 gene, which encodes a protein that binds to methylated DNA. Global genome
demethylation caused by targeted mutations in the DNA methyltransferase-1 (Dnmt1)
gene has shown that cytosine methylation plays essential roles in X-inactivation,
genomic imprinting and genome stabilization. The majority of genomic 5
methylcytosine is now known to enforce the transcriptional silence of the
enormous burden of transposons and retroviruses that have accumulated in the
mammalian genome. It has also become clear that programmed changes in methylation
patterns are less important in the regulation of mammalian development than was
previously believed. Although a number of outstanding questions have yet to be
answered (one of these questions involves the nature of the cues that designate
sites for methylation at particular stages of gametogenesis and early
development), studies of DNA methyltransferases are likely to provide further
insights into the biological functions of genomic methylation patterns.
PMID- 11005795
TI - Single nucleotide polymorphisms as tools in human genetics.
AB - The development of detailed single nucleotide polymorphism (SNP) maps of the
human genome coupled with high-throughput genotyping technologies may allow us to
unravel complex genetic traits, such as multifactorial disease or drug response,
over the next few years. Here we describe the current efforts to identify and
characterize the large numbers of SNPs required and discuss the practicalities of
association studies for the identification of genes involved in complex traits.
PMID- 11005796
TI - Counting cross-overs: characterizing meiotic recombination in mammals.
AB - Until recently, most of our understanding of meiotic recombination has come from
studies of lower eukaryotes. However, over the past few years several components
of the mammalian meiotic recombination pathway have been identified, and new
molecular and cytological approaches to the analysis of mammalian meiosis have
been developed. In this review, we discuss recent advances in three areas: the
application of new techniques to study genome-wide levels of recombination in
individual meioses; studies analyzing temporal aspects of the mammalian
recombination pathway; and studies linking the genesis of human trisomies to
alterations in meiotic exchange patterns.
PMID- 11005797
TI - The 22q11 deletion syndromes.
AB - DiGeorge syndrome, velocardiofacial syndrome and various other malformations have
been described in association with deletions and translocations involving human
chromosome 22q11. Many of the structural malformations observed are also seen in
animal models of neural crest disruption suggesting that the haplo-insufficiency
resulting from the deletion somehow affects this group of cells or their
interactions. Over the past few years it has been shown that the deletion
predisposes to a range of psychotic conditions prompting the hypothesis that the
deleted region may contain a predisposition locus for psychotic illness. The
DiGeorge chromosomal region has been entirely sequenced and many of the genes
mapping to the deletion interval have been studied in some detail. Despite these
efforts, no gene has yet been proved to play a defined role in the pathogenesis
of the syndrome. Current efforts are directed at the study of engineered
chromosome mouse models which offer the potential to dissect at least some of the
developmental pathways disrupted in this intriguing group of malformation
syndromes.
PMID- 11005798
TI - Homologous recombination as a mechanism for genome rearrangements: environmental
and genetic effects.
AB - Novel findings over the last 2 years have led to an increased emphasis on
homologous recombination (HR) as both a pathway for DNA repair and a cause for
genomic rearrangements. Indeed, environmental carcinogens increase the frequency
of HR, as can be observed when two copies of a duplicated sequence recombine to
delete the intervening sequences. Such HR events between dispersed homologous
sequences may result in not only deletions, but also gene duplications or
translocations. These types of genomic rearrangement have been observed to be the
cause of several different genetic diseases, including cancer. In reflection of
this, several genes have been identified that, when mutant, predispose an
individual to an increased frequency of cancer. These genes have been shown to be
either directly or indirectly involved in HR. In addition, HR is induced by a
wide variety of carcinogens, preferentially in proliferating cells. This fits the
most current models of recombination and its involvement in reinitiating stalled
replication forks. Thus, 'correct' HR repair may act with high fidelity, an
important issue for proliferating cells, but in the context of alternative
homologous partner sequences, 'aberrant' HR can cause genomic rearrangements with
dire consequences.
PMID- 11005799
TI - An update on genetic, structural and functional studies of arylamine N
acetyltransferases in eucaryotes and procaryotes.
AB - Arylamine N:-acetyltransferase (NAT) was first identified as the inactivator of
the anti-tubercular drug isoniazid. The enzyme was shown to catalyse the transfer
of an acetyl group from acetyl-CoA to the terminal nitrogen of the hydrazine
drug. The rate of inactivation of isoniazid was polymorphically distributed in
the population and was one of the first examples of pharmacogenetic variation.
NAT was identified recently in Mycobacterium tuberculosis and is a candidate for
modulating the response to isoniazid. Genome sequences have revealed many
homologous members of this unique family of enzymes. The first three-dimensional
structure of a member of the NAT family identifies a catalytic triad consisting
of aspartate, histidine and cysteine proposed to form the activation mechanism.
So far, all procaryotic NATs resemble the human enzyme which acetylates isoniazid
(NAT2). Human NAT2 is characteristic of drug-metabolizing enzymes: it is found in
liver and intestine. In humans and other mammals, there are up to three different
isoenzymes. If only one isoenzyme is present, it is like human NAT1. Human NAT1
and its murine equivalent specifically acetylate the folate catabolite p
aminobenzoylglutamate. NAT1 and its murine homologue each have a ubiquitous
tissue distribution and are expressed early in development at the blastocyst
stage. During murine embryonic development, NAT is expressed in the developing
neural tube. The proposed endogenous role of NAT in folate metabolism, and its
multi-allelic nature, indicate that its role in development should be assessed
further.
PMID- 11005800
TI - Zebrafish: bridging the gap between development and disease.
AB - The zebrafish has been the model of choice amongst developmental biologists for
many years. This small freshwater species offers many advantages to the study of
organ and tissue development that are not provided by other model systems.
Against this background, modern molecular genetic approaches are being applied to
expand the physical and genetic mapping of the zebrafish genome. These approaches
complement the large-scale mutagenic screens that have led to the isolation of
mutant phenotypes. Some of the phenotypes have been found to resemble human
disease states, while mapping and sequencing data have revealed zebrafish genes
with significant homology to human disease-causing genes. It is the realization
that the zebrafish offers an amenable system for understanding disease, as
opposed to development, that underpins this review. The adventitious
identification of disease phenotypes amongst zebrafish mutants and the important
area of deliberate disease modelling using transgenesis and gene targeting should
lead to a better application of the zebrafish as a vertebrate model of human
diseases.
PMID- 11005801
TI - Animal models of spinal muscular atrophy.
AB - Proximal spinal muscular atrophy (SMA) is the second most common autosomal
recessive inherited disorder in humans. It is the most common genetic cause of
infant mortality. As yet, there is no cure for this neuromuscular disorder which
affects the lower motor neurons and proximal muscles of the limbs and trunk. In
the last decade, significant advances have been made in understanding this
disease, from linkage analysis to isolating the defective gene and identifying
its protein product. This review summarizes the most recent advance in SMA
research: the development of animal models of the disease, in particular mouse
models of SMA. The SMA mice that we describe here present with symptoms similar
to those seen in SMA patients. They promise to further the understanding of the
molecular basis of this disease and demonstrate the feasibility of using the
intact SMN2 gene, found in all SMA patients, as a means of treating this
disorder.
PMID- 11005802
TI - Animal models for muscular dystrophy: valuable tools for the development of
therapies.
AB - Since the identification of dystrophin as the causative factor in Duchenne
muscular dystrophy, an increasing amount of information on the molecular basis of
muscular dystrophies has facilitated the division of these heterogeneous
disorders into distinct groups. As more light is being shed on the genes and
proteins involved in muscular dystrophy, diagnosis of patients has improved
enormously. In addition to naturally occurring animal models, a number of
genetically engineered murine models for muscular dystrophy have been generated.
These animal models have provided valuable clues to the understanding of the
pathogenesis of these disorders. Furthermore, as therapeutic approaches are being
developed, mutant animals represent good models in which they can be tested. The
present review focuses on the recent advancements of gene transfer-based
strategies, with a special emphasis on animal models for Duchenne and limb-girdle
muscular dystrophies.
PMID- 11005803
TI - Functional interaction of proliferating cell nuclear antigen with MSH2-MSH6 and
MSH2-MSH3 complexes.
AB - Eukaryotic DNA mismatch repair requires the concerted action of several proteins,
including proliferating cell nuclear antigen (PCNA) and heterodimers of MSH2
complexed with either MSH3 or MSH6. Here we report that MSH3 and MSH6, but not
MSH2, contain N-terminal sequence motifs characteristic of proteins that bind to
PCNA. MSH3 and MSH6 peptides containing these motifs bound PCNA, as did the
intact Msh2-Msh6 complex. This binding was strongly reduced when alanine was
substituted for conserved residues in the motif. Yeast strains containing alanine
substitutions in the PCNA binding motif of Msh6 or Msh3 had elevated mutation
rates, indicating that these interactions are important for genome stability.
When human MSH3 or MSH6 peptides containing the PCNA binding motif were added to
a human cell extract, mismatch repair activity was inhibited at a step preceding
DNA resynthesis. Thus, MSH3 and MSH6 interactions with PCNA may facilitate early
steps in DNA mismatch repair and may also be important for other roles of these
eukaryotic MutS homologs.
PMID- 11005804
TI - Insertion or deletion of a single residue in the strut sequence of Dictyostelium
myosin II abolishes strong binding to actin.
AB - The strut loop, one of the three loops that connects the upper and lower 50K
subdomains of myosin, plays a role as a "strut" to keep the relative disposition
of the two subdomains. A single residue was either inserted into or deleted from
this loop. The insertion or deletion mutation abolished the in vivo motor
functions of myosin, as revealed by the fact that the mutant myosins did not
complement the phenotypic defects of the myosin-null cells. In vitro studies of
purified full-length myosins and their subfragment-1s (S1s) revealed that the
insertion mutants virtually lost the strong binding to actin although their motor
functions in the absence of actin remained almost normal, showing that only the
hydrophobic actin-myosin association was selectively affected by the insertion
mutations. Unlike the insertion mutants, the deletion mutant showed defects both
in the strong-binding state and the rate-limiting step of ATPase cycle. These
results indicate the functional importance of the strut loop in establishing the
strong-binding state of myosin and thereby achieving successful power strokes.
PMID- 11005805
TI - Both the structure and DNA binding function of the barrier-to-autointegration
factor contribute to reconstitution of HIV type 1 integration in vitro.
AB - Retroviral integration is mediated by viral preintegration complexes (PICs), and
human immunodeficiency virus type 1 (HIV-1) PICs treated with high salt lose
their in vitro integration activity. Barrier-to-autointegration factor (BAF) is a
host protein that efficiently restores PIC activity, but the mechanism(s) by
which BAF participates in HIV-1 integration remains largely unknown. Here we
developed a gel shift assay to study BAF DNA binding, and analyzed 14 mutant
proteins containing substitutions of conserved residues for binding and PIC
reconstitution activities. Although wild-type BAF efficiently bound double
stranded DNA, binding to single-stranded DNA, RNA, or an RNA/DNA hybrid was not
detected, suggesting that BAF associates with retroviral cDNA relatively late
during reverse transcription. Although some of the BAF mutant proteins
efficiently bound DNA, others were defective for binding. Mutants that bound DNA
efficiently reconstituted HIV-1 integration, even though in one case binding was
just 0.2% of wild-type BAF. Although misfolded mutants did not reconstitute
integration, a structurally intact DNA binding-defective mutant displayed partial
activity at high BAF concentration. We therefore conclude that both BAF protein
structure and its DNA binding activity play roles in reconstituting HIV-1
integration in vitro.
PMID- 11005806
TI - Conformational and dynamic differences between actin filaments polymerized from
ATP- or ADP-actin monomers.
AB - Conformational and dynamic properties of actin filaments polymerized from ATP- or
ADP-actin monomers were compared by using fluorescence spectroscopic methods. The
fluorescence intensity of IAEDANS attached to the Cys(374) residue of actin was
smaller in filaments from ADP-actin than in filaments from ATP-actin monomers,
which reflected a nucleotide-induced conformational difference in subdomain 1 of
the monomer. Radial coordinate calculations revealed that this conformational
difference did not modify the distance of Cys(374) from the longitudinal filament
axis. Temperature-dependent fluorescence resonance energy transfer measurements
between donor and acceptor molecules on Cys(374) of neighboring actin protomers
revealed that the inter-monomer flexibility of filaments assembled from ADP-actin
monomers were substantially greater than the one of filaments from ATP-actin
monomers. Flexibility was reduced by phalloidin in both types of filaments.
PMID- 11005807
TI - Substrate-assisted catalysis of the PAR1 thrombin receptor. Enhancement of
macromolecular association and cleavage.
AB - Platelet activation and aggregation are mediated by thrombin cleavage of the
exodomain of the PAR1 receptor. The specificity of thrombin for PAR1 is enhanced
by binding to a hirudin-like region (Hir) located in the receptor exodomain.
Here, we examine the mechanism of thrombin-PAR1 recognition and cleavage by
steady-state kinetic measurements using soluble PAR1 N-terminal exodomains. We
determined that the primary role of the PAR1 Hir sequence is to reduce the
kinetic barriers to formation of the docked thrombin-PAR1 complex rather than to
form high affinity ground-state interactions. In addition, the exosite I-bound
Hir motif facilitates the productive interaction of the PAR1 (38)LDPR/SFL(44)
sequence with the active site of thrombin. This locking process is the most
energetically unfavorable step of the overall reaction. The subsequent
irreversible steps of peptide bond cleavage are rapid and allosterically enhanced
by the presence of the docked Hir sequence. Furthermore, the C-terminal exodomain
product of thrombin cleavage, corresponding to the activated receptor, binds
tightly to thrombin. This would suggest that an additional role of the Hir
sequence in the thrombin-activated receptor is to sequester thrombin to the
platelet surface and modulate cleavage of other platelet receptors such as the
PAR4 thrombin receptor, which lacks a functional Hir sequence.
PMID- 11005808
TI - The mechanism of heat shock activation of ERK mitogen-activated protein kinases
in the interleukin 3-dependent ProB cell line BaF3.
AB - We have investigated heat shock stimulation of MAPK cascades in an interleukin 3
dependent cell line, BaF3. Following exposure to 42 degrees C, the stress
activated JNK MAPKs were phosphorylated and activated, but p38 MAPKs remained
unaffected. Surprisingly, heat shock also activated ERK MAPKs in a potent (>60
fold), delayed (>30 min), and sustained (>/=120 min) manner. These
characteristics suggested a novel mechanism of ERK MAPK activation and became the
focus of this study. A MEK-specific inhibitor, PD98059, inhibited heat shock ERK
MAPK activation by >75%. Surprisingly, a role for Ras in the heat shock response
was eliminated by the failure of a dominant-negative Ras(Asn-17) mutant to
inhibit ERK MAPK activation and the failure to observe increases in Ras.GTP. Heat
shock also failed to stimulate activation of A-, B-, and c-Raf. Instead, a
serine/threonine phosphatase inhibitor, okadaic acid, activated ERK MAPK in a
similar manner to heat shock. Furthermore, pretreatment with suramin, generally
recognized as a broad range inhibitor of growth factor receptors, inhibited both
okadaic acid-stimulated and heat shock-stimulated ERK MAPK activity by >40%.
Inhibiting ERK MAPK activation during heat shock with PD98059 enhanced losses in
cell viability. These results demonstrate Ras- and Raf-independent ERK MAPK
activation maintains cell viability following heat shock.
PMID- 11005809
TI - Opposite functions for E2F1 and E2F4 in human epidermal keratinocyte
differentiation.
AB - Proteins of the retinoblastoma family (pRb, p107, and p130) modulate cell
proliferation, a function related to their capacity to control the activity of
the E2F transcription factor family. The Rb proteins also control cell
differentiation in different tissues. We have recently described their
involvement in human epidermal keratinocyte differentiation (Paramio, J. M.,
Lain, S., Segrelles, C., Lane, E. B. , and Jorcano, J. L. (1998) Oncogene 17, 949
957). Here we show that E2F proteins are also involved in this process. We found
that E2F1 and E2F4 are expressed differentially during the in vitro
differentiation of human epidermal keratinocytes, with the former uniformly
present throughout the process, whereas the second is predominantly expressed at
the onset of differentiation. This pattern is also observed in human skin by
confocal microscopy. Electrophoretic mobility shift assays and
immunoprecipitation experiments demonstrated that the complexes formed by E2F1
and E2F4 and Rb family proteins vary throughout in vitro keratinocyte
differentiation. In agreement with this observation, several E2F-responsive genes
are differentially regulated during this process. To test the functional
implications of these observations, we transfected HaCaT keratinocytes with
plasmids coding for E2F1 and E2F4. Transfected cells display opposite in vitro
differentiation properties. Although E2F1-transfected cells are unable to
differentiate, E2F4-transfected cells show an increased differentiation rate
compared with Neo-transfected control cells. Our data demonstrate that the
differential and coordinated expression and interaction of E2F and Rb proteins
modulate the process of epidermal differentiation and provide clear evidence that
members of the E2F family of transcription factors play specific and opposite
roles during cell differentiation.
PMID- 11005810
TI - Cks1 mediates vascular smooth muscle cell polyploidization.
AB - Vascular smooth muscle cells (VSMC) at capacitance arteries of hypertensive
individuals and animals undergo dramatic polyploidization that contributes toward
their hypertrophic phenotype. We report here the identification of a defective
mitotic spindle cell cycle checkpoint in VSMC isolated from capacitance arteries
of pre-hypertensive rats. These cells demonstrated a high predisposition to
polyploidization in culture and failed to maintain cyclin B protein levels in
response to colcemid, a mitotic inhibitor. Furthermore, this altered mitotic
spindle checkpoint status was associated with the overexpression of Cks1, a Cdc2
adapter protein that promotes cyclin B degradation. Cks1 up-regulation, cyclin B
down-regulation, and VSMC polyploidization were evidenced at the smooth muscle of
capacitance arteries of genetically hypertensive and Goldblatt-operated rats. In
addition, angiotensin II infusion dramatically increased Cks1 protein levels at
capacitance arteries of normotensive rats, and angiotensin II treatment of
isolated VSMC abrogated their ability to down-regulate Cks1 and maintain cyclin B
protein expression in response to colcemid. Finally, transduction of VSMC from
normotensive animals with a retrovirus that drives the expression of Cks1 was
sufficient to alter their mitotic spindle cell cycle checkpoint status and
promote unscheduled cyclin B metabolism, cell cycle re-entry, and
polyploidization. These data demonstrate that Cks1 regulates cyclin B metabolism
and ploidy in VSMC and may contribute to the understanding of the phenomena of
VSMC polyploidization during hypertension.
PMID- 11005811
TI - Mapping the binding site of colchicinoids on beta -tubulin. 2-Chloroacetyl-2
demethylthiocolchicine covalently reacts predominantly with cysteine 239 and
secondarily with cysteine 354.
AB - 2-Chloroacetyl-2-demethylthiocolchicine (2CTC) and 3-chloroacetyl-3
demethylthiocolchicine (3CTC) resemble colchicine in binding to tubulin and react
covalently with beta-tubulin, forming adducts with cysteine residues 239 and 354.
The adducts at Cys-239 are less stable than those at Cys-354 during formic acid
digestion. Extrapolating to zero time, the Cys-239 to Cys-354 adduct ratio is
77:23 for 2CTC and 27:73 for 3CTC. Using energy minimization modeling to dock
colchicinoids into the electron crystallographic model of beta-tubulin in
protofilaments (Nogales, E. , Wolf, S. G., and Downing, K. H. (1998) Nature 391,
199-203), we found two potential binding sites. At one, entirely encompassed
within beta-tubulin, the C2- and C3-oxygen atoms of 2CTC and 3CTC overlapped
poorly with those of colchicine and thiocolchicine, but distances from the
reactive carbon atoms of the analogs to the sulfur atoms of the cysteine residues
were qualitatively consistent with reactivity. The other potential binding site
was located at the alpha/beta interface. Here, the oxygen atoms of the analogs
overlapped well with those of colchicine, but relative distances of the reactive
carbons to the cysteine sulfur atoms did not correlate with the observed
reactivity. A significant conformational change must occur in the colchicine
binding site of tubulin in the transition from the unpolymerized to the
polymerized state.
PMID- 11005812
TI - Multiple amino acid substitutions allow DNA polymerases to synthesize RNA.
AB - DNA and RNA polymerase exhibit similarities in structures and catalytic
mechanisms, suggesting that both classes of enzymes are evolutionarily related.
To probe the biochemical and structure-function relationship between the two
classes of polymerases, a large library (200,000 members) of mutant Thermus
aquaticus DNA polymerase I (Taq pol I) was created containing random
substitutions within a portion of the dNTP binding site (motif A; amino acids 605
617), and a fraction of all selected active Taq pol I (291 of 8000) was tested
for the ability to incorporate successive ribonucleotides; 23 unique mutants that
added rNTPs into a growing polynucleotide chain were identified and sequenced.
These mutants, each containing one to four substitutions, incorporate
ribonucleotides at a efficiency approaching 10(3)-fold greater than that of wild
type Taq pol I. Several mutants added successive ribonucleotides and thus can
catalyze the synthesis of RNA. Sequence analysis of these mutants demonstrates
that at least two amino acid residues are involved in excluding ribonucleotides
from the active site. Interestingly, wild type DNA polymerases from several
distinct families selectively discriminate against rUTP. This study suggests that
current DNA and RNA polymerases could have evolved by divergent evolution from an
ancestor that shared a common mechanism for polynucleotide synthesis.
PMID- 11005813
TI - Mutational analysis of the Pyrococcus furiosus holliday junction resolvase hjc
revealed functionally important residues for dimer formation, junction DNA
binding, and cleavage activities.
AB - The Holliday junction cleavage protein, Hjc resolvase of Pyrococcus furiosus, is
the first Holliday junction resolvase to be discovered in Archaea. Although the
archaeal resolvase shares certain biochemical properties with other non-archaeal
junction resolvases, no amino acid sequence similarity has been identified. To
investigate the structure-function relationship of this new Holliday junction
resolvase, we constructed a series of mutant hjc genes using site-directed
mutagenesis targeted at the residues conserved among the archaeal orthologs. The
products of these mutant genes were purified to homogeneity. With analysis of the
activity of the mutant proteins to bind and cleave synthetic Holliday junctions,
one acidic residue, Glu-9, and two basic residues, Arg-10 and Arg-25, were found
to play critical roles in enzyme action. This is in addition to the three
conserved residues, Asp-33, Glu-46, and Lys-48, which are also conserved in the
motif found in the type II restriction endonuclease family proteins. Two aromatic
residues, Phe-68 and Phe-72, are important for the formation of the homodimer
probably through hydrophobic interactions. The results of these studies have
provided insights into the structure-function relationships of the archaeal
Holliday junction resolvase as well as the universality and diversity of the
Holliday junction cleavage reaction.
PMID- 11005814
TI - Characterization of proteoglycans of human placenta and identification of unique
chondroitin sulfate proteoglycans of the intervillous spaces that mediate the
adherence of Plasmodium falciparum-infected erythrocytes to the placenta.
AB - In pregnant women infected with Plasmodium falciparum, the infected red blood
cells (IRBCs) selectively accumulate in the intervillous spaces of placenta,
leading to poor fetal outcome and severe health complications in the mother.
Although chondroitin 4-sulfate is known to mediate IRBC adherence to placenta,
the natural receptor has not been identified. In the present study, the
chondroitin sulfate proteoglycans (CSPGs) of human placenta were purified and
structurally characterized, and adherence of IRBCs to these CSPGs investigated.
The data indicate that the placenta contains three distinct types of CSPGs:
significant quantities of uniquely low sulfated, extracellular CSPGs localized in
the intervillous spaces, minor amounts of two cell-associated CSPGs, and major
amounts of dermatan sulfate-like CSPGs of the fibrous tissue. Of the various
CSPGs isolated from the placenta, the low sulfated CSPGs of the intervillous
spaces most efficiently bind IRBCs. Based on IRBC adherence capacities and
localization patterns of various CSPGs, we conclude that the CSPGs of the
intervillous spaces are the receptors for placental IRBC adherence. The
identification and characterization of these CSPGs provide a valuable tool for
understanding the precise molecular interactions involved in placental IRBC
adherence and for the development of therapeutic strategies for maternal malaria.
In the accompanying paper (Alkhalil, A., Achur, R. N., Valiyaveettil, M.,
Ockenhouse, C. F., and Gowda, D. C. (2000) J. Biol. Chem. 275, 40357-40364), we
report the structural requirements for the IRBC adherence.
PMID- 11005815
TI - Structural requirements for the adherence of Plasmodium falciparum-infected
erythrocytes to chondroitin sulfate proteoglycans of human placenta.
AB - Plasmodium falciparum infection during pregnancy results in the accumulation of
infected red blood cells (IRBCs) in the placenta, leading to poor pregnancy
outcome. In the preceding paper (Achur, R. N., Valiyaveettil, M., Alkhalil, A.,
Ockenhouse, C. F., and Gowda, D. C. (2000) J. Biol. Chem. 275, 40344-40356), we
reported that unusually low sulfated chondroitin sulfate proteoglycans (CSPGs) in
the intervillous spaces of the placenta mediate the IRBC adherence. In this
study, we report the structural requirements for the adherence and the minimum
chondroitin 4-sulfate (C4S) structural motif that supports IRBC adherence.
Partially sulfated C4Ss with varying sulfate contents were prepared by solvolytic
desulfation of a fully sulfated C4S. These and other nonmodified C4Ss, with
different proportions of 4-, 6-, and nonsulfated disaccharide repeats, were
analyzed for inhibition of IRBC adherence to the placental CSPG. C4Ss containing
30-50% 4-sulfated and 50-70% nonsulfated disaccharide repeats efficiently
inhibited IRBC adherence; C6S had no inhibitory activity. Oligosaccharides of
varying sizes were prepared by the partial depolymerization of C4Ss containing
varying levels of 4-sulfation, and their ability to inhibit the IRBC adherence
was studied. Oligosaccharides with six or more disaccharide repeats inhibited
IRBC adherence to the same level as that of the intact C4Ss, indicating that a
dodecasaccharide is the minimum structural motif required for optimal IRBC
adherence. Of the C4S dodecasaccharides, only those with two or three sulfate
groups per molecule showed maximum IRBC inhibition. These data define the
structural requirements for the IRBC adherence to placental CSPGs with
implications for the development of therapeutics for maternal malaria.
PMID- 11005816
TI - Aminooxypentane addition to the chemokine macrophage inflammatory protein-1alpha
P increases receptor affinities and HIV inhibition.
AB - To enter its target cells, human immunodeficiency virus (HIV) must interact with
CD4 and one of a family of chemokine receptors. CCR5 is widely used by the virus
in this context, and its ligands can prevent HIV entry. Amino-terminal modified
chemokine variants, in particular AOP-RANTES (aminooxypentane-linked regulated on
activation normal T cell expressed and secreted), exhibit enhanced HIV entry
inhibition. We have previously demonstrated that a non-allelic isoform of
macrophage inflammatory protein (MIP)-1alpha, termed MIP-1alphaP, is the most
active naturally occurring inhibitor of HIV entry known. Here we report the
properties of a variant of MIP-1alphaP with an AOP group on the amino terminus.
We show that, like RANTES, the addition of AOP to MIP-1alphaP enhances its
interactions with CCR1 and CCR5, allows more effective internalization of CCR5,
and increases the ligand's potency as an inhibitor of HIV entry through CCR5.
Importantly, AOP-MIP-1alphaP is about 10-fold more active than AOP-RANTES at
inhibiting HIV entry, making it the most effective chemokine-based inhibitor of
HIV entry through CCR5 described to date. Surprisingly, the enhanced receptor
interactions of AOP-MIP-1alphaP do not translate into increased chemotaxis or
coupling to calcium ion fluxes, suggesting that this protein should be viewed as
a partial, rather than a full, agonist for CCR1 and CCR5.
PMID- 11005817
TI - Glucocorticoid receptor interaction with 14-3-3 and Raf-1, a proposed mechanism
for cross-talk of two signal transduction pathways.
AB - The glucocorticoid receptor (GR) functions as a ligand-dependent transcription
factor. In the present study we describe a specific immunoaffinity chromatography
purification of GR from liver cytosol from adrenalectomized rats that may be used
to identify hitherto unknown cytosolic GR interacting proteins. We have
identified the ubiquitously expressed 14-3-3 as well as Raf-1, a downstream
effector of Ras, as GR co-purifying proteins. In our semi-quantitative analysis
liganded/activated GR showed the strongest interaction with 14-3-3 and Raf-1, but
14-3-3 was also found to co-purify with GR in a nonliganded/nonactivated state.
By extensive salt washes we were also able to demonstrate that the glucocorticoid
induced interaction between GR, 14-3-3, and Raf-1, respectively, is remarkably
stable and withstood 2.4 m salt. The interaction between GR and 14-3-3 was also
verified by 14-3-3 co-immunoprecipitation studies. Our observations that GR and
Raf-1 are found within the same protein complex ("receptosome") in the cytoplasm
of rat liver cells could provide a mechanistic explanation for glucocorticoid
effects on the Raf-1-Ras signaling pathway.
PMID- 11005819
TI - Gene conversion (recombination) mediates expansions of CTG[middle dot]CAG
repeats.
AB - Genetic recombination is a robust mechanism for expanding CTG.CAG triplet repeats
involved in the etiology of hereditary neurological diseases (Jakupciak, J. P.,
and Wells, R. D. (1999) J. Biol. Chem. 274, 23468-23479). This two-plasmid
recombination system in Escherichia coli with derivatives of pUC19 and pACYC184
was used to investigate the effect of triplet repeat orientation on recombination
and extent of expansions; tracts of 36, 50, 80, and 36, 100, and 175 repeats in
length, respectively, in all possible permutations of length and in both
orientations (relative to the unidirectional replication origins) revealed little
or no effect of orientation of expansions. The extent of expansions was generally
severalfold the length of the progenitor tract and frequently exceeded the
combined length of the two tracts in the cotransformed plasmids. Expansions were
much more frequent than deletions. Repeat tracts bearing two G-to-A interruptions
(polymorphisms) within either 171- or 219-base pair tracts substantially reduced
the expansions compared with uninterrupted repeat tracts of similar lengths. Gene
conversion, rather than crossing over, was the recombination mechanism. Prior
studies showed that DNA replication, repair, and tandem duplication also mediated
genetic instabilities of the triplet repeat sequence. However, gene conversion
(recombinational repair) is by far the most powerful expansion mechanism. Thus,
we propose that gene conversion is the likely expansion mechanism for myotonic
dystrophy, spinocerebellar ataxia type 8, and fragile X syndrome.
PMID- 11005818
TI - Evidence for a two-electron transfer using the all-ferrous Fe protein during
nitrogenase catalysis.
AB - The nitrogenase-catalyzed H(2) evolution and acetylene-reduction reactions using
Ti(III) and dithionite (DT) as reductants were examined and compared under a
variety of conditions. Ti(III) is known to make the all-ferrous Fe protein
([Fe(4)S(4)](0)) and lowers the amount of ATP hydrolyzed during nitrogenase
catalysis by approximately 2-fold. Here we further investigate this behavior and
present results consistent with the Fe protein in the [Fe(4)S(4)](0) redox state
transferring two electrons ([Fe(4)S(4)](2+)/[Fe(4)S(4)](0)) per MoFe protein
interaction using Ti(III) but transferring only one electron
([Fe(4)S(4)](2+)/[Fe(4)S(4)](1+)) using DT. MoFe protein specific activity was
measured as a function of Fe:MoFe protein ratio for both a one- and a two
electron transfer reaction, and nearly identical curves were obtained. However,
Fe protein specific activity curves as a function of MoFe:Fe protein ratio showed
two distinct reactivity patterns. With DT as reductant, typical MoFe inhibition
curves were obtained for operation of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](1+) redox
couple, but with Ti(III) as reductant the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox
couple was functional and MoFe inhibition was not observed at high MoFe:Fe
protein ratios. With Ti(III) as reductant, nitrogenase catalysis produced
hyperbolic curves, yielding a V(max) for the Fe protein specific activity of
about 3200 nmol of H(2) min(-1) mg(-1) Fe protein, significantly higher than for
reactions conducted with DT as reductant. Lag phase experiments (Hageman, R. V.,
and Burris, R. H. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 2699-2702) were
carried out at MoFe:Fe protein ratios of 100 and 300 using both DT and Ti(III). A
lag phase was observed for DT but, with Ti(III) product formation, began
immediately and remained linear for over 30 min. Activity measurements using Av
Cp heterologous crosses were examined using both DT and Ti(III) as reductants to
compare the reactivity of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](1+) and
[Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couples and both were inactive. The results
are discussed in terms of the Fe protein transferring two electrons per MoFe
protein encounter using the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couple with
Ti(III) as reductant.
PMID- 11005820
TI - Determinants for calmodulin binding on voltage-dependent Ca2+ channels.
AB - Calmodulin, bound to the alpha(1) subunit of the cardiac L-type calcium channel,
is required for calcium-dependent inactivation of this channel. Several
laboratories have suggested that the site of interaction of calmodulin with the
channel is an IQ-like motif in the carboxyl-terminal region of the alpha(1)
subunit. Mutations in this IQ motif are linked to L-type Ca(2+) current (I(Ca))
facilitation and inactivation. IQ peptides from L, P/Q, N, and R channels all
bind Ca(2+)calmodulin but not Ca(2+)-free calmodulin. Another peptide
representing a carboxyl-terminal sequence found only in L-type channels
(designated the CB domain) binds Ca(2+)calmodulin and enhances Ca(2+)-dependent
I(Ca) facilitation in cardiac myocytes, suggesting the CB domain is functionally
important. Calmodulin blocks the binding of an antibody specific for the CB
sequence to the skeletal muscle L-type Ca(2+) channel, suggesting that this is a
calmodulin binding site on the intact protein. The binding of the IQ and CB
peptides to calmodulin appears to be competitive, signifying that the two
sequences represent either independent or alternative binding sites for
calmodulin rather than both sequences contributing to a single binding site.
PMID- 11005821
TI - SUMO-1 modification of bovine papillomavirus E1 protein is required for
intranuclear accumulation.
AB - The E1 protein is a multifunctional, origin-binding helicase that is essential
for replication of papillomaviruses. Recently, bovine papillomavirus E1 was shown
to be post-translationally modified by the addition of the SUMO-1 polypeptide.
Here we show that the site of sumoylation maps to lysine residue 514. This lysine
and the flanking sequences are well conserved in human papillomavirus (HPV) E1
proteins. Both HPV1a and HPV18 E1 proteins are substrates for sumoylation in
vitro, which is consistent with this modification being a general property of E1
proteins. Mutations, which impair the sumoylation of bovine papillomavirus E1,
prevent normal nuclear accumulation of E1 with a concomitant loss of replication
capacity. These results suggest that sumoylation plays a role in nuclear
transport and could regulate the E1 replication function by controlling access to
the nuclear replication domains.
PMID- 11005822
TI - The putative coiled coil domain of the phi 29 terminal protein is a major
determinant involved in recognition of the origin of replication.
AB - The linear double-stranded genome of phage phi29 contains a terminal protein (TP)
covalently linked at each 5' DNA end, called parental TP. Initiation of phi29 DNA
replication starts with the recognition of the origins of replication,
constituted by the parental TP-containing DNA ends, by a heterodimer containing
phi29 DNA polymerase and primer TP. It has been argued that origin recognition
involves protein-protein interactions between parental and primer TP. Analysis of
the TP sequence revealed that the region between amino acids 84 and 118 has a
high probability to form an amphipatic alpha-helix that could be involved in the
interaction between parental and primer TP. Therefore, this TP region may be
important for origin recognition. To test this hypothesis we introduced various
mutations in the predicted amphipatic alpha-helix and analyzed the functionality
of the corresponding purified TP mutants. The results obtained show that the
identified putative amphipatic alpha-helix of TP is an important determinant
involved in origin recognition.
PMID- 11005823
TI - Copper- and zinc-containing superoxide dismutase can act as a superoxide
reductase and a superoxide oxidase.
AB - The copper- and zinc-containing superoxide dismutase can catalyze the oxidation
of ferrocyanide by O(2) as well as the reduction of ferricyanide by O(2). Thus,
it can act as a superoxide dismutase (SOD), a superoxide reductase (SOR), and a
superoxide oxidase (SOO). The human manganese-containing SOD does not exert SOR
or SOO activities with ferrocyanide or ferricyanide as the redox partners. It is
possible that some biological reductants can take the place of ferrocyanide and
can also interact with human manganese-containing superoxide dismutase, thus
making the SOR activity a reality for both SODs. The consequences of this
possibility vis a vis H(2)O(2) production, the overproduction of SODs, and the
role of copper- and zinc-containing superoxide dismutase mutations in causing
familial amyotrophic lateral sclerosis are discussed, as well as the likelihood
that the biologically effective SOD mimics, as described to date, actually
function as SORs.
PMID- 11005824
TI - Molecular modeling and site-directed mutagenesis define the catalytic motif in
human gamma -glutamyl hydrolase.
AB - Human gamma-glutamyl hydrolase (hGH) is a central enzyme in folyl and
antifolylpoly-gamma-glutamate metabolism, which functions by catalyzing the
cleavage of the gamma-glutamyl chain of substrates. We previously reported that
Cys-110 is essential for activity. Using the sequence of hGH as a query,
alignment searches of protein data bases were made using the SSearch and TPROBE
programs. Significant similarity was found between hGH and the glutamine
amidotransferase type I domain of Escherichia coli carbamoyl phosphate
synthetase. The resulting hypothesis is that the catalytic fold of hGH is similar
to the folding of this domain in carbamoyl phosphate synthetase. This model
predicts that Cys-110 of hGH is the active site nucleophile and forms a catalytic
triad with residues His-220 and Glu-222. The hGH mutants C110A, H220A, and E222A
were prepared. Consistent with the model, mutants C110A and H220A were inactive.
However, the V(max) of the E222A hGH mutant was reduced only 6-fold relative to
the wild-type enzyme. The model also predicted that His-171 in hGH may be
involved in substrate binding. The H171N hGH mutant was found to have a 250-fold
reduced V(max). These studies to determine the catalytic mechanism begin to
define the three dimensional interactions of hGH with poly-gamma-glutamate
substrates.
PMID- 11005825
TI - Evidence for sequential action of cdc7 and cdk2 protein kinases during initiation
of DNA replication in Xenopus egg extracts.
AB - To investigate how the protein kinase cdc7 stimulates DNA replication in
metazoans, a soluble cell-free replication system derived from Xenopus eggs was
used. DNA was incubated in egg cytosol to form prereplication complexes and then
in nucleoplasmic extract to initiate DNA synthesis. We find that cdc7 is greatly
enriched in nucleoplasmic extract and that this high concentration is essential
for efficient DNA replication, supporting previous models that the nucleus
activates replication indirectly by sequestering essential components. cdc7 binds
to chromatin at the G(1)/S transition before initiation occurs, and it
dissociates from chromatin as S phase progresses. The chromatin association of
cdc7 requires chromatin-bound MCM. In turn, cdc7 is required to load the
initiation factor cdc45 onto the DNA. Finally, efficient replication is observed
when chromatin is exposed first to cdc7 and then to cdk2 but not when it is
exposed to cdk2 before cdc7. Therefore, the cdc7- and cdk2-dependent initiation
steps can be separated, indicating the existence of a novel, stable initiation
intermediate. Moreover, the data suggest that cdk2 can only act after cdc7 has
executed its function.
PMID- 11005826
TI - Structural basis of the drastically increased initial electron transfer rate in
the reaction center from a Rhodopseudomonas viridis mutant described at 2.00-A
resolution.
AB - It has previously been shown that replacement of the residue His L168 with Phe
(HL168F) in the Rhodopseudomonas viridis reaction center (RC) leads to an
unprecedented drastic acceleration of the initial electron transfer rate. Here we
describe the determination of the x-ray crystal structure at 2.00-A resolution of
the HL168F RC. The electron density maps confirm that a hydrogen bond from the
protein to the special pair is removed by this mutation. Compared with the wild
type RC, the acceptor of this hydrogen bond, the ring I acetyl group of the
"special pair" bacteriochlorophyll, D(L), is rotated, and its acetyl oxygen is
found 1.1 A closer to the bacteriochlorophyll-Mg(2+) of the other special pair
bacteriochlorophyll, D(M). The rotation of this acetyl group and the increased
interaction between the D(L) ring I acetyl oxygen and the D(M)-Mg(2+) provide the
structural basis for the previously observed 80-mV decrease in the D(+)/D redox
potential and the drastically increased rate of initial electron transfer to the
accessory bacteriochlorophyll, B(A). The high quality of the electron density
maps also allowed a reliable discussion of the mode of binding of the triazine
herbicide terbutryn at the binding site of the secondary quinone, Q(B).
PMID- 11005827
TI - Counting probability distributions: differential geometry and model selection.
AB - A central problem in science is deciding among competing explanations of data
containing random errors. We argue that assessing the "complexity" of
explanations is essential to a theoretically well-founded model selection
procedure. We formulate model complexity in terms of the geometry of the space of
probability distributions. Geometric complexity provides a clear intuitive
understanding of several extant notions of model complexity. This approach allows
us to reconceptualize the model selection problem as one of counting explanations
that lie close to the "truth." We demonstrate the usefulness of the approach by
applying it to the recovery of models in psychophysics.
PMID- 11005828
TI - Cooperative regulation of light-harvesting complex II phosphorylation via the
plastoquinol and ferredoxin-thioredoxin system in chloroplasts.
AB - Light induces phosphorylation of photosystem II (PSII) proteins in chloroplasts
by activating the protein kinase(s) via reduction of plastoquinone and the
cytochrome b(6)f complex. The recent finding of high-light-induced inactivation
of the phosphorylation of chlorophyll a/b-binding proteins (LHCII) of the PSII
antenna in floated leaf discs, but not in vitro, disclosed a second regulatory
mechanism for LHCII phosphorylation. Here we show that this regulation of LHCII
phosphorylation is likely to be mediated by the chloroplast ferredoxin
thioredoxin system. We present a cooperative model for the function of the two
regulation mechanisms that determine the phosphorylation level of the LHCII
proteins in vivo, based on the following results: (i) Chloroplast thioredoxins f
and m efficiently inhibit LHCII phosphorylation. (ii) A disulfide bond in the
LHCII kinase, rather than in its substrate, may be a target component regulated
by thioredoxin. (iii) The target disulfide bond in inactive LHCII kinase from
dark-adapted leaves is exposed and easily reduced by external thiol mediators,
whereas in the activated LHCII kinase the regulatory disulfide bond is hidden.
This finding suggests that the activation of the kinase induces a conformational
change in the enzyme. The active state of LHCII kinase prevails in chloroplasts
under low-light conditions, inducing maximal phosphorylation of LHCII proteins in
vivo. (iv) Upon high-light illumination of leaves, the target disulfide bond
becomes exposed and thus is made available for reduction by thioredoxin,
resulting in a stable inactivation of LHCII kinase.
PMID- 11005829
TI - Genes identified by an expression screen of the vector mosquito Anopheles gambiae
display differential molecular immune response to malaria parasites and bacteria.
AB - We performed a gene expression screen of the entire transcriptome of the major
African malaria vector Anopheles gambiae for immune response genes in adult
female mosquitoes, which is the developmental stage infected by malaria
parasites. Mosquitoes were immune-stimulated for subtractive cloning by treatment
with bacterial lipopolysaccharide, a potent and general elicitor of the innate
immune response, and by injury. The screen yielded a highly enriched cDNA library
in which more than half of the clones were immune responsive. In this paper, we
describe 23 immune-regulated genes, including putative protease inhibitors,
serine proteases, regulatory molecules, and a number of genes without known
relatives. A molecule related to the protease inhibitor alpha-2-macroglobulin
responded strongly to malaria parasite infection, but displayed little or no
response to bacteria, whereas other genes exhibited the inverse pattern. These
results indicate that the insect immune system discriminates between molecular
signals specific to infection with bacteria and malaria parasites.
PMID- 11005830
TI - A biosensor assay for studying ligand-membrane receptor interactions: binding of
antibodies and HIV-1 Env to chemokine receptors.
AB - The HIV envelope (Env) protein mediates entry into cells by binding CD4 and an
appropriate coreceptor, which triggers structural changes in Env that lead to
fusion between the viral and cellular membranes. The major HIV-1 coreceptors are
the seven transmembrane domain chemokine receptors CCR5 and CXCR4. The type of
coreceptor used by a virus strain is an important determinant of viral tropism
and pathogenesis, and virus-receptor interactions can be therapeutic targets.
However, Envs from many virus strains interact with CXCR4 and CCR5 with low
affinity such that direct study of this important interaction is difficult if not
impossible using standard cell-surface binding techniques. We have developed an
approach that makes it possible to study ligand binding to membrane proteins,
including Env-coreceptor interactions, using an optical biosensor. CCR5, CXCR4,
and other membrane proteins were incorporated into retrovirus particles, which
were purified and attached to the biosensor surface. Binding of conformationally
sensitive antibodies as well as Env to these receptors was readily detected. The
equilibrium dissociation constant for the interaction between an Env derived from
the prototype HIV-1 strain IIIB for CXCR4 was approximately 500 nM, explaining
the difficulty in measuring this interaction using standard equilibrium binding
techniques. Retroviral pseudotypes represent easily produced, stable, homogenous
structures that can be used to present a wide array of single and multiple
membrane-spanning proteins in a native lipid environment for biosensor studies,
thus avoiding the need for detergent solubilization, purification, and
reconstitution. The approach should have general applicability and can be used to
correlate Env-receptor binding constants to viral tropism and pathogenesis.
PMID- 11005832
TI - Proliferation is necessary for both repair and mutation in transgenic mouse
cells.
AB - Proliferating cells are often presumed to be more mutable than quiescent cells
because they have less time to repair DNA damage before DNA replication. Direct
tests of this hypothesis have been confounded by the need for cell division
before a mutation can be detected. We have avoided this problem by showing that
the Big Blue mouse cell line permits the dynamic quantification of both lesions
and mutations in the complete absence of cell division. These cells carry the
bacterial lacI gene in a lambda shuttle vector. Mutant plaques recovered by in
vitro packaging of the mouse DNA can arise from mutations sustained either in
mouse cells or in the bacteria. The proportion of mutant phage contained within a
mutant plaque can distinguish these two types of mutation. Mutations formed in
mouse cells yield >90% mutant phage because both DNA strands are mutant. On the
other hand, mutations formed in the bacteria from adducted DNA yield =50%
mutant phage, because one of the DNA strands is wild type. Immediately after
exposure to a test mutagen, ethylnitrosourea, all induced mutations were formed
in the bacteria, but after approximately one cell division, the reverse was true
and all mutations arose in the mouse cells. Only one-fifth as many mutations were
recovered from quiescent cells and all arose in the bacteria, showing that the
mouse cells made no mutations in the absence of proliferation. Surprisingly, the
mouse cells did not repair any of the premutagenic damage during 4 days of
quiescence. When these quiescent cells were induced to proliferate, however, both
repair and mutation fixation ensued.
PMID- 11005831
TI - Arabidopsis basic leucine zipper transcription factors involved in an abscisic
acid-dependent signal transduction pathway under drought and high-salinity
conditions.
AB - The induction of the dehydration-responsive Arabidopsis gene, rd29B, is mediated
mainly by abscisic acid (ABA). Promoter analysis of rd29B indicated that two ABA
responsive elements (ABREs) are required for the dehydration-responsive
expression of rd29B as cis-acting elements. Three cDNAs encoding basic leucine
zipper (bZIP)-type ABRE-binding proteins were isolated by using the yeast one
hybrid system and were designated AREB1, AREB2, and AREB3 (ABA-responsive element
binding protein). Transcription of the AREB1 and AREB2 genes is up-regulated by
drought, NaCl, and ABA treatment in vegetative tissues. In a transient
transactivation experiment using Arabidopsis leaf protoplasts, both the AREB1 and
AREB2 proteins activated transcription of a reporter gene driven by ABRE. AREB1
and AREB2 required ABA for their activation, because their transactivation
activities were repressed in aba2 and abi1 mutants and enhanced in an era1
mutant. Activation of AREBs by ABA was suppressed by protein kinase inhibitors.
These results suggest that both AREB1 and AREB2 function as transcriptional
activators in the ABA-inducible expression of rd29B, and further that ABA
dependent posttranscriptional activation of AREB1 and AREB2, probably by
phosphorylation, is necessary for their maximum activation by ABA. Using cultured
Arabidopsis cells, we demonstrated that a specific ABA-activated protein kinase
of 42-kDa phosphorylated conserved N-terminal regions in the AREB proteins.
PMID- 11005833
TI - Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II
tetramers.
AB - We characterized antigen-specific CD4(+) T cells in six patients with treatment
resistant Lyme arthritis, using an HLA-DRB1*0401 major histocompatibility complex
(MHC) class II tetramer covalently loaded with OspA(164-175), an immunodominant
epitope of Borrelia burgdorferi. Direct analysis of OspA-tetramer binding CD4(+)
cells in patients expressing the HLA-DRB1*0401 allele revealed frequencies of
between <0.005 and 0.1% in peripheral blood (n = 6), and between <0.005 and 3.1%
in synovial fluid (n = 3). OspA-tetramer(+)CD4(+) cells were directly cloned at 1
cell per well and expanded by mitogen and IL-2 on allogeneic feeder cells. As
measured by [(3)H]thymidine incorporation, 95% of 168 T cell clones from synovial
fluid binding the OspA-tetramer were antigen-reactive. Clones generated from
peripheral blood revealed a different pattern of responsiveness when compared
with clones generated from synovial fluid, as measured by proliferation, IFN
gamma, and IL-13 secretion. These clones, selected on the basis of their peptide
binding, also responded to whole protein, but with a different cytokine profile.
Our studies demonstrate that MHC class II tetramers can be used in humans to
directly identify, isolate, and characterize antigen-reactive T cells from an
inflammatory compartment.
PMID- 11005834
TI - Remarkable species diversity in Malagasy mouse lemurs (primates, Microcebus).
AB - Phylogenetic analysis of mtDNA sequence data confirms the observation that
species diversity in the world's smallest living primate (genus Microcebus) has
been greatly underestimated. The description of three species new to science, and
the resurrection of two others from synonymy, has been justified on morphological
grounds and is supported by evidence of reproductive isolation in sympatry. This
taxonomic revision doubles the number of recognized mouse lemur species. The
molecular data and phylogenetic analyses presented here verify the revision and
add a historical framework for understanding mouse lemur species diversity.
Phylogenetic analysis revises established hypotheses of ecogeographic constraint
for the maintenance of species boundaries in these endemic Malagasy primates.
Mouse lemur clades also show conspicuous patterns of regional endemism, thereby
emphasizing the threat of local deforestation to Madagascar's unique
biodiversity.
PMID- 11005835
TI - Ecological basis of extinction risk in birds: habitat loss versus human
persecution and introduced predators.
AB - Understanding the ecological mechanisms that underlie extinction is fundamental
to conservation. It is well established that not all taxa are equally vulnerable
to extinction, but the reasons for these differences are poorly understood. This
may be, in part, because different taxa are threatened by different mechanisms.
Theoretically, sources of extinction risk that perturb the balance between
fecundity and longevity, such as human persecution and introduced predators,
should be particularly hazardous for taxa that have slow rates of population
growth. In contrast, sources of extinction risk that reduce niche availability,
such as habitat loss, should represent a particular threat to taxa that are
ecologically specialized. Here we test these predictions by using a phylogenetic
comparative method and a database on 95 families of birds. As theory predicts,
extinction risk incurred through persecution and introduced predators is
associated with large body size and long generation time but is not associated
with degree of specialization, whereas extinction risk incurred through habitat
loss is associated with habitat specialization and small body size but not with
generation time. These results demonstrate the importance of considering
separately the multiple mechanisms that underlie contemporary patterns of
extinction. They also reveal why it has previously proven so difficult to
identify simple ecological correlates of overall extinction risk.
PMID- 11005836
TI - Differential role of transcription-coupled repair in UVB-induced G2 arrest and
apoptosis in mouse epidermis.
AB - Nucleotide excision repair (NER), apoptosis, and cell-cycle regulation are major
defense mechanisms against the carcinogenic effects of UVB light. NER eliminates
UVB-induced DNA photolesions via two subpathways: global genome repair (GGR) and
transcription-coupled repair (TCR). Defects in NER result in the human disorders
xeroderma pigmentosum (XP) and Cockayne syndrome (CS), displaying severe UV
sensitivity and in the case of XP, cancer proneness. We investigated the impact
of deficiencies in NER subpathways on apoptosis, hyperplasia, and cell cycle
progression in the epidermis of UVB-exposed CS group B (Csb(-/-)) mice (no TCR),
XP group C (Xpc(-/-)) mice (no GGR), and XP group A (Xpa(-/-)) mice (no TCR and
no GGR). On UVB treatment (250 J/m(2)), Xpa(-/-) and Csb(-/-) mice revealed an
extensive apoptotic response in the skin, a blockage of cell cycle progression of
epidermal cells, and strong hyperplasia. Interestingly, the absence of this
apoptotic response in the skin of wild-type and Xpc(-/-) mice coincided with the
ability of epidermal cells to enter the S phase. However, only epidermal cells of
Xpc(-/-) mice subsequently became arrested in the G(2) phase. Our data
demonstrate that TCR (and/or restoration of UVB-inhibited transcription) enables
damaged cells to progress through S phase and prevents the induction of apoptosis
and hyperplasia. G(2) arrest is manifest only under conditions of proficient TCR
in combination with deficient GGR, indicating that epidermal cells become
arrested in the G(2) phase as a result of persisting damage in their genome.
PMID- 11005837
TI - The state diagram for cell adhesion under flow: leukocyte rolling and firm
adhesion.
AB - Leukocyte adhesion under flow in the microvasculature is mediated by binding
between cell surface receptors and complementary ligands expressed on the surface
of the endothelium. Leukocytes adhere to endothelium in a two-step mechanism:
rolling (primarily mediated by selectins) followed by firm adhesion (primarily
mediated by integrins). Using a computational method called "Adhesive Dynamics,"
we have simulated the adhesion of a cell to a surface in flow, and elucidated the
relationship between receptor-ligand functional properties and the dynamics of
adhesion. We express this relationship in a state diagram, a one-to-one map
between the biophysical properties of adhesion molecules and various adhesive
behaviors. Behaviors that are observed in simulations include firm adhesion,
transient adhesion (rolling), and no adhesion. We varied the dissociative
properties, association rate, bond elasticity, and shear rate and found that the
unstressed dissociation rate, k(r)(o), and the bond interaction length, gamma,
are the most important molecular properties controlling the dynamics of adhesion.
Experimental k(r)(o) and gamma values from the literature for molecules that are
known to mediate rolling adhesion fall within the rolling region of the state
diagram. We explain why L-selectin-mediated rolling, which has faster k(r)(o)
than other selectins, is accompanied by a smaller value for gamma. We also show
how changes in association rate, shear rate, and bond elasticity alter the
dynamics of adhesion. The state diagram (which must be mapped for each receptor
ligand system) presents a concise and comprehensive means of understanding the
relationship between bond functional properties and the dynamics of adhesion
mediated by receptor-ligand bonds.
PMID- 11005838
TI - Classes of small-world networks.
AB - We study the statistical properties of a variety of diverse real-world networks.
We present evidence of the occurrence of three classes of small-world networks:
(a) scale-free networks, characterized by a vertex connectivity distribution that
decays as a power law; (b) broad-scale networks, characterized by a connectivity
distribution that has a power law regime followed by a sharp cutoff; and (c)
single-scale networks, characterized by a connectivity distribution with a fast
decaying tail. Moreover, we note for the classes of broad-scale and single-scale
networks that there are constraints limiting the addition of new links. Our
results suggest that the nature of such constraints may be the controlling factor
for the emergence of different classes of networks.
PMID- 11005839
TI - Worldwide DNA sequence variation in a 10-kilobase noncoding region on human
chromosome 22.
AB - Human DNA sequence variation data are useful for studying the origin, evolution,
and demographic history of modern humans and the mechanisms of maintenance of
genetic variability in human populations, and for detecting linkage association
of disease. Here, we report worldwide variation data from a approximately 10
kilobase noncoding autosomal region. We identified 75 variant sites in 64 humans
(128 sequences) and 463 variant sites among the human, chimpanzee, and orangutan
sequences. Statistical tests suggested that the region is selectively neutral.
The average nucleotide diversity (pi) across the region was 0.088% among all of
the human sequences obtained, 0.085% among African sequences, and 0.082% among
non-African sequences, supporting the view of a low nucleotide diversity (
approximately 0.1%) in humans. The comparable pi value in non-Africans to that in
Africans indicates no severe bottleneck during the evolution of modern non
Africans; however, the possibility of a mild bottleneck cannot be excluded
because non-Africans showed considerably fewer variants than Africans. The
present and two previous large data sets all show a strong excess of low
frequency variants in comparison to that expected from an equilibrium population,
indicating a relatively recent population expansion. The mutation rate was
estimated to be 1.15 x 10(-9) per nucleotide per year. Estimates of the long-term
effective population size N(e) by various statistical methods were similar to
those in other studies. The age of the most recent common ancestor was estimated
to be approximately 1.29 million years ago among all of the sequences obtained
and approximately 634,000 years ago among the non-African sequences, providing
the first evidence from a noncoding autosomal region for ancient human histories,
even among non-Africans.
PMID- 11005840
TI - Photoperiodic information acquired and stored in vivo is retained in vitro by a
circadian oscillator, the avian pineal gland.
AB - Endogenous circadian rhythms have been described in a wide range of organisms
from prokaryotes to man. Although basic circadian mechanisms at the molecular
level are genetically fixed, certain properties of circadian rhythms at the
organismic level can be modified by environmental conditions and subsequently
retained for some time, even in organisms shielded from 24-hr environmental
variations. To investigate the capacity of animals to acquire and store
photoperiodic information, we examined activity and melatonin rhythms in house
sparrows during synchronization to two different photoperiods and during
subsequent prolonged darkness. Under constant environmental conditions, intact
animals continued to have long feeding activity times when previously exposed to
long days and short feeding activity times when previously exposed to short days.
Correspondingly, significantly different durations of elevated melatonin in the
plasma directly reflected the differences in night length during synchronization
as well as during prolonged darkness. Additionally, we found a significant
difference in the amplitude of the nocturnal melatonin signal, which also was
conserved in prolonged darkness. To investigate whether the photoperiodic
experience of an intact animal can be "memorized" by an isolated component of its
circadian pacemaking system, we have investigated in vitro melatonin release
during continuous darkness from explanted pineal glands of house sparrows after
in vivo synchronization to two distinct photoperiods. Differences in the
durations of elevated melatonin occurred during the first two cycles in culture
and a difference in melatonin amplitude was detectable during the first night in
culture. Our data indicate that photoperiodic patterns imposed on sparrows during
in vivo synchronization can be maintained as an internal representation of time
within the isolated pineal gland. Hence, the pineal gland, as one of the most
significant components of the songbird circadian pacemaker, not only has the
capacity to autonomously produce circadian rhythms of melatonin release but also
is capable of storing biologically meaningful information experienced during
previous cycles.
PMID- 11005841
TI - gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol,
inhibit cyclooxygenase activity in macrophages and epithelial cells.
AB - Cyclooxygenase-2 (COX-2)-catalyzed synthesis of prostaglandin E(2) (PGE(2)) plays
a key role in inflammation and its associated diseases, such as cancer and
vascular heart disease. Here we report that gamma-tocopherol (gammaT) reduced
PGE(2) synthesis in both lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages
and IL-1beta-treated A549 human epithelial cells with an apparent IC(50) of 7.5
and 4 microM, respectively. The major metabolite of dietary gammaT, 2,7,8
trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), also exhibited an
inhibitory effect, with an IC(50) of approximately 30 microM in these cells. In
contrast, alpha-tocopherol at 50 microM slightly reduced (25%) PGE(2) formation
in macrophages, but had no effect in epithelial cells. The inhibitory effects of
gammaT and gamma-CEHC stemmed from their inhibition of COX-2 activity, rather
than affecting protein expression or substrate availability, and appeared to be
independent of antioxidant activity. gamma-CEHC also inhibited PGE(2) synthesis
when exposed for 1 h to COX-2-preinduced cells followed by the addition of
arachidonic acid (AA), whereas under similar conditions, gammaT required an 8- to
24-h incubation period to cause the inhibition. The inhibitory potency of gammaT
and gamma-CEHC was diminished by an increase in AA concentration, suggesting that
they might compete with AA at the active site of COX-2. We also observed a
moderate reduction of nitrite accumulation and suppression of inducible nitric
oxide synthase expression by gammaT in lipopolysaccharide-treated macrophages.
These findings indicate that gammaT and its major metabolite possess anti
inflammatory activity and that gammaT at physiological concentrations may be
important in human disease prevention.
PMID- 11005842
TI - Intracellular unesterified arachidonic acid signals apoptosis.
AB - Cyclooxygenase-2 (COX-2) is up-regulated in many cancers and is a rate-limiting
step in colon carcinogenesis. Nonsteroidal antiinflammatory drugs, which inhibit
COX-2, prevent colon cancer and cause apoptosis. The mechanism for this response
is not clear, but it might result from an accumulation of the substrate,
arachidonic acid, an absence of a prostaglandin product, or diversion of the
substrate into another pathway. We found that colon adenocarcinomas overexpress
another arachidonic acid-utilizing enzyme, fatty acid-CoA ligase (FACL) 4, in
addition to COX-2. Exogenous arachidonic acid caused apoptosis in colon cancer
and other cell lines, as did triacsin C, a FACL inhibitor. In addition,
indomethacin and sulindac significantly enhanced the apoptosis-inducing effect of
triacsin C. These findings suggested that unesterified arachidonic acid in cells
is a signal for induction of apoptosis. To test this hypothesis, we engineered
cells with inducible overexpression of COX-2 and FACL4 as "sinks" for
unesterified arachidonic acid. Activation of the enzymatic sinks blocked
apoptosis, and the reduction of cell death was inversely correlated with the
cellular level of arachidonic acid. Inhibition of the COX-2 component by
nonsteroidal antiinflammatory drugs restored the apoptotic response. Cell death
caused by exposure to tumor necrosis factor alpha or to calcium ionophore also
was prevented by removal of unesterified arachidonic acid. We conclude that the
cellular level of unesterified arachidonic acid is a general mechanism by which
apoptosis is regulated and that COX-2 and FACL4 promote carcinogenesis by
lowering this level.
PMID- 11005843
TI - Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated
expression of c-Myc in vivo.
AB - Overexpression of c-Myc in immortalized cells increases cell proliferation,
inhibits cell differentiation, and promotes cell transformation. Recent evidence
suggests that these effects, however, do not necessarily occur when c-Myc is
overexpressed in primary mammalian cells. We sought to determine the immediate
effects of transient overexpression of c-Myc in primary cells in vivo by using
recombinant adenovirus to overexpress human MYC in mouse liver. Mice were
intravenously injected with adenoviruses encoding MYC (Ad/Myc), E2F-1 (Ad/E2F-1),
or beta-galactosidase (Ad/LacZ). Transgene expression was detectable 4 days after
injection. Expression of ectopic c-Myc was immediately accompanied by enlarged
and dysmorphic hepatocytes in the absence of significant cell proliferation or
apoptosis. These findings were not present in the livers of mice injected with
Ad/E2F-1 or Ad/LacZ. Prominent hepatocyte nuclei and nucleoli were associated
with the up-regulation of large- and small-subunit ribosomal and nucleolar genes,
suggesting that c-Myc may induce their expression to increase cell mass. Our
studies support a role for c-Myc in the in vivo control of vertebrate cell size
and metabolism independent of cell proliferation.
PMID- 11005844
TI - Intracellular delivery of phosphoinositides and inositol phosphates using
polyamine carriers.
AB - Phosphoinositide signaling regulates events in endocytosis and exocytosis,
vesicular trafficking of proteins, transduction of extracellular signals,
remodeling of the actin cytoskeleton, regulation of calcium flux, and apoptosis.
Obtaining mechanistic insights in living cells is impeded by the membrane
impermeability of these anionic lipids. We describe a carrier system for
intracellular delivery of phosphoinositide polyphosphates (PIP(n)s) and
fluorescently labeled PIP(n)s into living cells, such that intracellular
localization can be directly observed. Preincubation of PIP(n)s or inositol
phosphates with carrier polyamines produced complexes that entered mammalian,
plant, yeast, bacterial, and protozoal cells in seconds to minutes via a
nonendocytic mechanism. Time-dependent transit of both PIP(n)s and the carrier to
specific cytosolic and nuclear compartments was readily visualized by
fluorescence microscopy. Platelet-derived growth factor treatment of NIH 3T3
fibroblasts containing carrier-delivered phosphatidylinositol 4,5-bisphosphate
[PtdIns(4, 5)P(2)]-7-nitrobenz-2-oxa-1,3-diazole resulted in the redistribution
of the fluorescent signal, suggesting that fluorescent PtdIns(4, 5)P(2) was a
substrate for phospholipase C. We also observed a calcium flux in NIH 3T3 cells
when complexes of carrier and PtdIns(4, 5)P(2) or inositol 1,4,5-trisphosphate
were added extracellularly. This simple intracellular delivery system allows for
the efficient translocation of biologically active PIP(n)s, inositol phosphates,
and their fluorescent derivatives into living cells in a physiologically relevant
context.
PMID- 11005845
TI - A structural basis for drug-induced long QT syndrome.
AB - Mutations in the HERG K(+) channel gene cause inherited long QT syndrome (LQT), a
disorder of cardiac repolarization that predisposes affected individuals to
lethal arrhythmias [Curran, M. E. , Splawski, I., Timothy, K. W., Vincent, G. M.,
Green, E. D. & Keating, M. T. (1995) Cell 80, 795-804]. Acquired LQT is far more
common and is most often caused by block of cardiac HERG K(+) channels by
commonly used medications [Roden, D. M., Lazzara, R., Rosen, M., Schwartz, P. J.,
Towbin, J. & Vincent, G. M. (1996) Circulation 94, 1996-2012]. It is unclear why
so many structurally diverse compounds block HERG channels, but this undesirable
side effect now is recognized as a major hurdle in the development of new and
safe drugs. Here we use alanine-scanning mutagenesis to determine the structural
basis for high-affinity drug block of HERG channels by MK-499, a
methanesulfonanilide antiarrhythmic drug. The binding site, corroborated with
homology modeling, is comprised of amino acids located on the S6 transmembrane
domain (G648, Y652, and F656) and pore helix (T623 and V625) of the HERG channel
subunit that face the cavity of the channel. Other compounds that are
structurally unrelated to MK-499, but cause LQT, also were studied. The
antihistamine terfenadine and a gastrointestinal prokinetic drug, cisapride,
interact with Y652 and F656, but not with V625. The aromatic residues of the S6
domain that interact with these drugs (Y652 and F656) are unique to eag/erg K(+)
channels. Other voltage-gated K(+) (Kv) channels have Ile and Val (Ile) in the
equivalent positions. These findings suggest a possible structural explanation
for how so many commonly used medications block HERG but not other Kv channels
and should facilitate the rational design of drugs devoid of HERG channel binding
activity.
PMID- 11005846
TI - Induction of photosensitivity in neonatal rat pineal gland.
AB - Pineal glands removed from neonatal rats at 5, 7, and 9 days of age and explanted
into short-term culture, synthesized melatonin when stimulated with
norepinephrine (NE); their melatonin synthesis could not be suppressed with
bright white light. Dispersed pineal cell cultures or pineal explants prepared
from 1-day-old neonates and held in culture for 7 or 9 days also synthesized
melatonin when stimulated with NE, but in these cases melatonin synthesis was
significantly suppressed by light, demonstrating that the pineals had become
photosensitive while in culture. The development of photosensitivity in culture
could be partially or completely abolished by the continuous presence of 1 or 10
microm of NE in the culture medium. The pineals of all nonmammalian vertebrates
are photoreceptive, whereas those of mammals do not normally respond to light. We
hypothesize that a mechanism to suppress pineal photosensitivity by using NE
released from sympathetic nerve endings evolved early in the history of mammals.
PMID- 11005847
TI - Bacteriocin AS-48, a microbial cyclic polypeptide structurally and functionally
related to mammalian NK-lysin.
AB - The solution structure of bacteriocin AS-48, a 70-residue cyclic polypeptide from
Enterococcus faecalis, consists of a globular arrangement of five alpha-helices
enclosing a compact hydrophobic core. The head-to-tail union lies in the middle
of helix 5, a fact that is shown to have a pronounced effect on the stability of
the three-dimensional structure. Positive charges in the side chains of residues
in helix 4 and in the turn linking helix 4 to helix 5 form a cluster that most
probably determine its antibacterial activity by promoting pore formation in cell
membranes. A similar five-helix structural motif has been found in the
antimicrobial NK-lysin, an effector polypeptide of T and natural killer (NK)
cells. Bacteriocin AS-48 lacks the three disulfide bridges characteristic of the
saposin fold present in NK-lysin, and has no sequence homology with it.
Nevertheless, the similar molecular architecture and high positive charge
strongly suggest a common mechanism of antibacterial action.
PMID- 11005848
TI - Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term
survival and late-stage therapy.
AB - Ribozyme-directed cleavage of mutant mRNAs appears to be a potentially effective
therapeutic measure for dominantly inherited diseases. We previously demonstrated
that two ribozymes targeted to the P23H mutation in rhodopsin slow photoreceptor
degeneration in transgenic rats for up to 3 months of age when injected before
significant degeneration at postnatal day (P) 15. We now have explored whether
ribozyme rescue persists at older ages, and whether ribozymes are effective when
injected later in the degeneration after significant photoreceptor cell loss.
Recombinant adeno-associated virus (rAAV) vectors incorporating a proximal bovine
rod opsin promoter were used to transfer either hairpin or hammerhead ribozyme
genes to photoreceptors. For the study of long-term survival, rAAV was
administered by subretinal injection at P15, and the rats were allowed to live up
to 8 months of age. For the study of late-stage gene transfer, rAAV was
administered at P30 or P45, when 40-45% of the photoreceptors already had
degenerated. Eyes were examined functionally by the electroretinogram and
structurally by morphometric analysis. When injected at P15, expression of either
ribozyme markedly slowed the rate of photoreceptor degeneration for at least 8
months and resulted in significantly greater electroretinogram amplitudes at
least up to P180. When injected at P30 or P45, virtually the same number of
photoreceptors survived at P130 as when injected at P15. Ribozyme rescue appears
to be a potentially effective, long-term therapy for autosomal dominant retinal
degeneration and is highly effective even when the gene transfer is done after
significant photoreceptor cell loss.
PMID- 11005849
TI - Glycosylphosphatidylinositol biosynthesis validated as a drug target for African
sleeping sickness.
PMID- 11005850
TI - Mice, microarrays, and the genetic diversity of the brain.
PMID- 11005851
TI - Breaking the affinity ceiling for antibodies and T cell receptors.
PMID- 11005852
TI - Viral interference with IL-1 and toll signaling.
PMID- 11005853
TI - Molecular mechanisms underlying differential odor responses of a mouse olfactory
receptor.
AB - The prevailing paradigm for G protein-coupled receptors is that each receptor is
narrowly tuned to its ligand and closely related agonists. An outstanding problem
is whether this paradigm applies to olfactory receptor (ORs), which is the
largest gene family in the genome, in which each of 1,000 different G protein
coupled receptors is believed to interact with a range of different odor
molecules from the many thousands that comprise "odor space." Insights into how
these interactions occur are essential for understanding the sense of smell. Key
questions are: (i) Is there a binding pocket? (ii) Which amino acid residues in
the binding pocket contribute to peak affinities? (iii) How do affinities change
with changes in agonist structure? To approach these questions, we have combined
single-cell PCR results [Malnic, B., Hirono, J., Sato, T. & Buck, L. B. (1999)
Cell 96, 713-723] and well-established molecular dynamics methods to model the
structure of a specific OR (OR S25) and its interactions with 24 odor compounds.
This receptor structure not only points to a likely odor-binding site but also
independently predicts the two compounds that experimentally best activate OR
S25. The results provide a mechanistic model for olfactory transduction at the
molecular level and show how the basic G protein-coupled receptor template is
adapted for encoding the enormous odor space. This combined approach can
significantly enhance the identification of ligands for the many members of the
OR family and also may shed light on other protein families that exhibit broad
specificities, such as chemokine receptors and P450 oxidases.
PMID- 11005854
TI - Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase:
structure-based mechanism of conversion.
AB - Mammalian xanthine oxidoreductases, which catalyze the last two steps in the
formation of urate, are synthesized as the dehydrogenase form xanthine
dehydrogenase (XDH) but can be readily converted to the oxidase form xanthine
oxidase (XO) by oxidation of sulfhydryl residues or by proteolysis. Here, we
present the crystal structure of the dimeric (M(r), 290,000) bovine milk XDH at
2.1-A resolution and XO at 2.5-A resolution and describe the major changes that
occur on the proteolytic transformation of XDH to the XO form. Each molecule is
composed of an N-terminal 20-kDa domain containing two iron sulfur centers, a
central 40-kDa flavin adenine dinucleotide domain, and a C-terminal 85-kDa
molybdopterin-binding domain with the four redox centers aligned in an almost
linear fashion. Cleavage of surface-exposed loops of XDH causes major structural
rearrangement of another loop close to the flavin ring (Gln 423Lys 433). This
movement partially blocks access of the NAD substrate to the flavin adenine
dinucleotide cofactor and changes the electrostatic environment of the active
site, reflecting the switch of substrate specificity observed for the two forms
of this enzyme.
PMID- 11005855
TI - Identification of a third distinct estrogen receptor and reclassification of
estrogen receptors in teleosts.
AB - This paper describes three distinct estrogen receptor (ER) subtypes: ERalpha,
ERbeta, and a unique type, ERgamma, cloned from a teleost fish, the Atlantic
croaker Micropogonias undulatus; the first identification of a third type of
classical ER in vertebrate species. Phylogenetic analysis shows that ERgamma
arose through gene duplication from ERbeta early in the teleost lineage and
indicates that ERgamma is present in other teleosts, although it has not been
recognized as such. The Atlantic croaker ERgamma shows amino acid differences in
regions important for ligand binding and receptor activation that are conserved
in all other ERgammas. The three ER subtypes are genetically distinct and have
different distribution patterns in Atlantic croaker tissues. In addition, ERbeta
and ERgamma fusion proteins can each bind estradiol-17beta with high affinity.
The presence of three functional ERs in one species expands the role of ER
multiplicity in estrogen signaling systems and provides a unique opportunity to
investigate the dynamics and mechanisms of ER evolution.
PMID- 11005856
TI - CXR, a chicken xenobiotic-sensing orphan nuclear receptor, is related to both
mammalian pregnane X receptor (PXR) and constitutive androstane receptor (CAR).
AB - Nuclear receptors constitute a large family of ligand-modulated transcription
factors that mediate cellular responses to small lipophilic molecules, including
steroids, retinoids, fatty acids, and exogenous ligands. Orphan nuclear receptors
with no known endogenous ligands have been discovered to regulate drug-mediated
induction of cytochromes P450 (CYP), the major drug-metabolizing enzymes. Here,
we report the cloning of an orphan nuclear receptor from chicken, termed chicken
xenobiotic receptor (CXR), that is closely related to two mammalian xenobiotic
activated receptors, the pregnane X receptor (PXR) and the constitutive
androstane receptor (CAR). Expression of CXR is restricted to tissues where drug
induction of CYPs predominantly occurs, namely liver, kidney, small intestine,
and colon. Furthermore, CXR binds to a previously identified phenobarbital
responsive enhancer unit (PBRU) in the 5'-flanking region of the chicken CYP2H1
gene. A variety of drugs, steroids, and chemicals activate CXR in CV-1 monkey
cell transactivation assays. The same agents induce PBRU-dependent reporter gene
expression and CYP2H1 transcription in a chicken hepatoma cell line. These
results provide convincing evidence for a major role of CXR in the regulation of
CYP2H1 and add a member to the family of xenobiotic-activated orphan nuclear
receptors.
PMID- 11005857
TI - Tid1/Rdh54 promotes colocalization of rad51 and dmc1 during meiotic
recombination.
AB - Two RecA homologs, Rad51 and Dmc1, assemble as cytologically visible complexes
(foci) at the same sites on meiotic chromosomes. Time course analysis confirms
that co-foci appear and disappear as the single predominant form. A large
fraction of co-foci are eliminated in a red1 mutant, which is expected as a
characteristic of the interhomolog-specific recombination pathway. Previous
studies suggested that normal Dmc1 loading depends on Rad51. We show here that a
mutation in TID1/RDH54, encoding a RAD54 homolog, reduces Rad51-Dmc1
colocalization relative to WT. A rad54 mutation, in contrast, has relatively
little effect on RecA homolog foci except when strains also contain a tid1/rdh54
mutation. The role of Tid1/Rdh54 in coordinating RecA homolog assembly may be
very direct, because Tid1/Rdh54 is known to physically bind both Dmc1 and Rad51.
Also, Dmc1 foci appear early in a tid1/rdh54 mutant. Thus, Tid1 may normally act
with Rad51 to promote ordered RecA homolog assembly by blocking Dmc1 until Rad51
is present. Finally, whereas double-staining foci predominate in WT nuclei, a
subset of nuclei with expanded chromatin exhibit individual Rad51 and Dmc1 foci
side-by-side, suggesting that a Rad51 homo-oligomer and a Dmc1 homo-oligomer
assemble next to one another at the site of a single double-strand break (DSB)
recombination intermediate.
PMID- 11005858
TI - sqv-3, -7, and -8, a set of genes affecting morphogenesis in Caenorhabditis
elegans, encode enzymes required for glycosaminoglycan biosynthesis.
AB - sqv (squashed vulva) genes comprise a set of eight independent loci in
Caenorhabditis elegans required zygotically for the invagination of vulval
epithelial cells and maternally for normal oocyte formation and embryogenesis.
Sequencing of sqv-3, sqv-7, and sqv-8 suggested a role for the encoded proteins
in glycolipid or glycoprotein biosynthesis. Using a combination of in vitro
analysis of SQV enzymatic activities, sqv(+)-mediated rescue of vertebrate cell
lines, and biochemical characterization of sqv mutants, we show that sqv-3, -7,
and -8 all affect the biosynthesis of glycosaminoglycans and therefore compromise
the function of one specific class of glycoconjugates, proteoglycans. These
findings establish the importance of proteoglycans and their associated
glycosaminoglycans in epithelial morphogenesis and patterning during C. elegans
development.
PMID- 11005859
TI - Predicting species diversity in tropical forests.
AB - A fundamental question in ecology is how many species occur within a given area.
Despite the complexity and diversity of different ecosystems, there exists a
surprisingly simple, approximate answer: the number of species is proportional to
the size of the area raised to some exponent. The exponent often turns out to be
roughly 1/4. This power law can be derived from assumptions about the relative
abundances of species or from notions of self-similarity. Here we analyze the
largest existing data set of location-mapped species: over one million,
individually identified trees from five tropical forests on three continents.
Although the power law is a reasonable, zeroth-order approximation of our data,
we find consistent deviations from it on all spatial scales. Furthermore,
tropical forests are not self-similar at areas =50 hectares. We develop an
extended model of the species-area relationship, which enables us to predict
large-scale species diversity from small-scale data samples more accurately than
any other available method.
PMID- 11005860
TI - Purifying selection and birth-and-death evolution in the ubiquitin gene family.
AB - Ubiquitin is a highly conserved protein that is encoded by a multigene family. It
is generally believed that this gene family is subject to concerted evolution,
which homogenizes the member genes of the family. However, protein homogeneity
can be attained also by strong purifying selection. We therefore studied the
proportion (p(S)) of synonymous nucleotide differences between members of the
ubiquitin gene family from 28 species of fungi, plants, and animals. The results
have shown that p(S) is generally very high and is often close to the saturation
level, although the protein sequence is virtually identical for all ubiquitins
from fungi, plants, and animals. A small proportion of species showed a low level
of p(S) values, but these values appeared to be caused by recent gene
duplication. It was also found that the number of repeat copies of the gene
family varies considerably with species, and some species harbor pseudogenes.
These observations suggest that the members of this gene family evolve almost
independently by silent nucleotide substitution and are subjected to birth-and
death evolution at the DNA level.
PMID- 11005861
TI - Roles of a conserved arginine residue of DsbB in linking protein disulfide-bond
formation pathway to the respiratory chain of Escherichia coli.
AB - The active-site cysteines of DsbA, the periplasmic disulfide-bond-forming enzyme
of Escherichia coli, are kept oxidized by the cytoplasmic membrane protein DsbB.
DsbB, in turn, is oxidized by two kinds of quinones (ubiquinone for aerobic and
menaquinone for anaerobic growth) in the electron-transport chain. We describe
the isolation of dsbB missense mutations that change a highly conserved arginine
residue at position 48 to histidine or cysteine. In these mutants, DsbB functions
reasonably well aerobically but poorly anaerobically. Consistent with this
conditional phenotype, purified R48H exhibits very low activity with menaquinone
and an apparent Michaelis constant (K(m)) for ubiquinone seven times greater than
that of the wild-type DsbB, while keeping an apparent K(m) for DsbA similar to
that of wild-type enzyme. From these results, we propose that this highly
conserved arginine residue of DsbB plays an important role in the catalysis of
disulfide bond formation through its role in the interaction of DsbB with
quinones.
PMID- 11005862
TI - Robust gut-specific gene expression in transgenic Aedes aegypti mosquitoes.
AB - Genetic modification of the vectorial capacity of mosquito vectors of human
disease requires promoters capable of driving gene expression with appropriate
tissue and stage specificity. We report on the characterization in transgenic
Aedes aegypti of two mosquito gut-specific promoters. A 1.4-kb DNA fragment
adjacent to the 5' end of the coding region of the Ae. aegypti carboxypeptidase
(AeCP) gene and a corresponding 3.4-kb DNA fragment at the 5' end of the
Anopheles gambiae carboxypeptidase (AgCP) gene were linked to a firefly
luciferase reporter gene and introduced into the Ae. aegypti germ line by using
Hermes and mariner (Mos1) transposons. Six independent transgenic lines were
obtained with the AeCP construct and one with the AgCP construct. Luciferase mRNA
and protein were abundantly expressed in the guts of transgenic mosquitoes in
four of the six AeCP lines and in the AgCP line. Expression of the reporter gene
was gut-specific and reached peak levels at about 24 h post-blood ingestion. The
AeCP and AgCP promoters can be used to drive the expression of genes that hinder
parasite development in the mosquito gut.
PMID- 11005863
TI - Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA
class I allele.
AB - NY-ESO-1 elicits frequent antibody responses in cancer patients, accompanied by
strong CD8(+) T cell responses against HLA-A2-restricted epitopes. To broaden the
range of cancer patients who can be assessed for immunity to NY-ESO-1, a general
method was devised to detect T cell reactivity independent of prior
characterization of epitopes. A recombinant adenoviral vector encoding the full
cDNA sequence of NY-ESO-1 was used to transduce CD8-depleted peripheral blood
lymphocytes as antigen-presenting cells. These modified antigen-presenting cells
were then used to restimulate memory effector cells against NY-ESO-1 from the
peripheral blood of cancer patients. Specific CD8(+) T cells thus sensitized were
assayed on autologous B cell targets infected with a recombinant vaccinia virus
encoding NY-ESO-1. Strong polyclonal responses were observed against NY-ESO-1 in
antibody-positive patients, regardless of their HLA profile. Because the vectors
do not cross-react immunologically, only responses to NY-ESO-1 were detected. The
approach described here allows monitoring of CD8(+) T cell responses to NY-ESO-1
in the context of various HLA alleles and has led to the definition of NY-ESO-1
peptides presented by HLA-Cw3 and HLA-Cw6 molecules.
PMID- 11005865
TI - Antibodies have the intrinsic capacity to destroy antigens.
AB - Research throughout the last century has led to a consensus as to the strategy of
the humoral component of the immune system. The essence is that, for killing, the
antibody molecule activates additional systems that respond to antibody-antigen
union. We now report that the immune system seems to have a previously
unrecognized chemical potential intrinsic to the antibody molecule itself. All
antibodies studied, regardless of source or antigenic specificity, can convert
molecular oxygen into hydrogen peroxide, thereby potentially aligning recognition
and killing within the same molecule. Aside from pointing to a new chemical arm
for the immune system, these results may be important to the understanding of how
antibodies evolved and what role they may play in human diseases.
PMID- 11005864
TI - T-cell receptor antagonists induce Vav phosphorylation by selective activation of
Fyn kinase.
AB - T cell receptor (TCR) antagonists inhibit antigen-induced T cell activation and
by themselves fail to induce phenotypic changes associated with T cell
activation. However, we have recently shown that TCR antagonists are inducers of
antigen-presenting cell (APC)-T cell conjugates. The signaling pathway associated
with this cytoskeleton-dependent event appears to involve tyrosine
phosphorylation and activation of Vav. In this study, we investigated the role
played by the protein tyrosine kinases Fyn, Lck, and ZAP-70 in antagonist-induced
signaling pathway. Antagonist stimulation increased tyrosine phosphorylation and
kinase activity of Fyn severalfold, whereas little or no increase in Lck and ZAP
70 activity was observed. Second, TCR stimulation of Lck(-), Fyn(hi) Jurkat cells
induced strong tyrosine phosphorylation of Vav. In contrast, minimal increase in
tyrosine phosphorylation of Vav was observed in Lck(hi), Fyn(lo) Jurkat cells.
Finally, study of T cells from a Fyn-deficient TCR transgenic mouse also showed
that Fyn was required for tyrosine phosphorylation and activation of Vav induced
by both antagonist and agonist peptides. The deficiency in Vav phosphorylation in
Fyn-deficient T cells was associated with a defect in the formation of APC-T cell
conjugates when T cells were stimulated with either agonist or antagonist
peptide. We conclude from these results that Vav is a selective substrate for
Fyn, especially under conditions of low-affinity TCR-mediated signaling, and that
this signaling pathway involving Fyn, Vav, and Rac-1 is required for the
cytoskeletal reorganization that leads to T cell-APC conjugates and the formation
of the immunologic synapse.
PMID- 11005866
TI - A first trial of retrospective collaboration for positional cloning in complex
inheritance: assay of the cytokine region on chromosome 5 by the consortium on
asthma genetics (COAG).
AB - The central problem of complex inheritance is to map oligogenes for disease
susceptibility, integrating linkage and association over samples that differ in
several ways. Combination of evidence over multiple samples with 1,037 families
supports loci contributing to asthma susceptibility in the cytokine region on 5q
[maximum logarithm of odds (lod) = 2.61 near IL-4], but no evidence for atopy.
The principal problems with retrospective collaboration on linkage appear to have
been solved, providing far more information than a single study. A multipoint lod
table evaluated at commonly agreed reference loci is required for both
collaboration and metaanalysis, but variations in ascertainment, pedigree
structure, phenotype definition, and marker selection are tolerated. These
methods are invariant with statistical methods that increase the power of lods
and are applicable to all diseases, motivating collaboration rather than
competition. In contrast to linkage, positional cloning by allelic association
has yet to be extended to multiple samples, a prerequisite for efficient
combination with linkage and the greatest current challenge to genetic
epidemiology.
PMID- 11005867
TI - Antiretroviral resistance during successful therapy of HIV type 1 infection.
AB - HIV type 1 (HIV-1) drug resistance mutations were selected during antiretroviral
therapy successfully suppressing plasma HIV-1 RNA to <50 copies/ml. New resistant
mutant subpopulations were identified by clonal sequencing analyses of viruses
cultured from blood cells. Drug susceptibility tests showed that biological
clones of virus with the mutations acquired during successful therapy had
increased resistance. Each of the five subjects with new resistant mutants had
evidence of some residual virus replication during highly active antiretroviral
therapy (HAART), based on transient episodes of plasma HIV-1 RNA > 50 copies/ml
and virus env gene sequence changes. Each had received a suboptimal regimen
before starting HAART. Antiretroviral-resistant HIV-1 can be selected from
residual virus replication during HAART in the absence of sustained rebound of
plasma HIV-1 RNA.
PMID- 11005868
TI - Microglial activation precedes acute neurodegeneration in Sandhoff disease and is
suppressed by bone marrow transplantation.
AB - Sandhoff disease is a lysosomal storage disorder characterized by the absence of
beta-hexosaminidase and storage of G(M2) ganglioside and related glycolipids in
the central nervous system. The glycolipid storage causes severe
neurodegeneration through a poorly understood pathogenic mechanism. In
symptomatic Sandhoff disease mice, apoptotic neuronal cell death was prominent in
the caudal regions of the brain. cDNA microarray analysis to monitor gene
expression during neuronal cell death revealed an upregulation of genes related
to an inflammatory process dominated by activated microglia. Activated microglial
expansion, based on gene expression and histologic analysis, was found to precede
massive neuronal death. Extensive microglia activation also was detected in a
human case of Sandhoff disease. Bone marrow transplantation of Sandhoff disease
mice suppressed both the explosive expansion of activated microglia and the
neuronal cell death without detectable decreases in neuronal G(M2) ganglioside
storage. These results suggest a mechanism of neurodegeneration that includes a
vigorous inflammatory response as an important component. Thus, this lysosomal
storage disease has parallels to other neurodegenerative disorders, such as
Alzheimer's and prion diseases, where inflammatory processes are believed to
participate directly in neuronal cell death.
PMID- 11005869
TI - Enrichment for murine keratinocyte stem cells based on cell surface phenotype.
AB - The identification and physical isolation of epithelial stem cells is critical to
our understanding of their growth regulation during homeostasis, wound healing,
and carcinogenesis. These stem cells remain poorly characterized because of the
absence of specific molecular markers that permit us to distinguish them from
their progeny, the transit amplifying (TA) cells, which have a more restricted
proliferative potential. Cell kinetic analyses have permitted the identification
of murine keratinocyte stem cells (KSCs) as slowly cycling cells that retain
[(3)H]thymidine ([(3)H]Tdr) label, termed label-retaining cells (LRCs), whereas
TA cells are visualized as rapidly cycling cells after a single pulse of
[(3)H]Tdr, termed pulse-labeled cells (PLCs). Here, we report on the successful
separation of KSCs from TA cells through the combined use of in vivo cell kinetic
analysis and fluorescence-activated cell sorting. Specifically, we demonstrate
that murine dorsal keratinocytes characterized by their high levels of alpha(6)
integrin and low to undetectable expression of the transferrin receptor (CD71)
termed alpha(6)(bri)CD71(dim) cells, are enriched for epithelial stem cells
because they represent a minor ( approximately 8%) and quiescent subpopulation of
small blast-like cells, with a high nuclear:cytoplasmic ratio, containing
approximately 70% of label-retaining cells, the latter being a well documented
characteristic of stem cells. Conversely, TA cells could be enriched in a
phenotypically distinct subpopulation termed alpha(6)(bri)CD71(bri), representing
the majority ( approximately 60%) of basal keratinocytes that are actively
cycling, and importantly contain approximately 70% of [(3)H]Tdr pulse-labeled
cells. Importantly, immunostaining of dorsal skin revealed the presence of
CD71(dim) cells in the hair follicle bulge region, a well documented location for
KSCs.
PMID- 11005870
TI - Rapid induction of senescence in human cervical carcinoma cells.
AB - Expression of the bovine papillomavirus E2 regulatory protein in human cervical
carcinoma cell lines repressed expression of the resident human papillomavirus E6
and E7 oncogenes and within a few days caused essentially all of the cells to
synchronously display numerous phenotypic markers characteristic of cells
undergoing replicative senescence. This process was accompanied by marked but in
some cases transient alterations in the expression of cell cycle regulatory
proteins and by decreased telomerase activity. We propose that the human
papillomavirus E6 and E7 proteins actively prevent senescence from occurring in
cervical carcinoma cells, and that once viral oncogene expression is
extinguished, the senescence program is rapidly executed. Activation of
endogenous senescence pathways in cancer cells may represent an alternative
approach to treat human cancers.
PMID- 11005871
TI - The essential protein encoded by the UL31 gene of herpes simplex virus 1 depends
for its stability on the presence of UL34 protein.
AB - To pursue an earlier observation that the protein encoded by the U(L)34 gene
binds to intermediate chain of dynein, we constructed a series of mutants from
which sequences encoding the entire protein (DeltaU(L)34) or amino-terminal
[U(L)34Delta(3-119)] or carboxyl-terminal [U(L)34Delta(245-275)] domains were
deleted. The mutant lacking the sequence encoding the carboxyl-terminal domain
grew in all cell lines tested. The two other mutants replicated only in cell type
dependent manner and poorly. Rescue of DeltaU(L)34 mutant with a fragment that
does not encompass the U(L)31 ORF restored wild-type phenotype. U(L)34 protein
interacts physically with U(L)31, and the U(L)31 deletion mutant appears to have
a phenotype similar to that of U(L)34 deletion mutant. Experiments designed to
determine whether the phenotypes of the deletion mutants have a common base
revealed that cells infected with the DeltaU(L)34 mutant accumulate U(L)31 RNA
but not the corresponding protein. The U(L)31 protein accumulated, however, to
near wild-type virus-infected cell levels in cells infected with DeltaU(L)34
mutant and treated with the MG132 proteosomal inhibitor at 6 h after infection.
This is evidence that the stability of an essential viral protein requires the
presence of another protein. The observation raises the bar for identification of
gene function on the basis of analyses of the phenotype of mutants in which the
gene has been deleted or rendered inoperative.
PMID- 11005872
TI - Cerebral protein synthesis in a genetic mouse model of phenylketonuria.
AB - Local rates of cerebral protein synthesis (lCPS(leu)) were measured with the
quantitative autoradiographic [1-(14)C]leucine method in a genetic mouse model
(Pah(enu2)) of phenylketonuria. As in the human disease, Pah(enu2) mice have a
mutation in the gene for phenylalanine hydroxylase. We compared adult homozygous
(HMZ) and heterozygous (HTZ) Pah(enu2) mice with the background strain (BTBR).
Arterial plasma concentrations of phenylalanine (Phe) were elevated in both HMZ
and HTZ mutants by 21 times and 38%, respectively. In the total acid-soluble pool
in brain concentrations of Phe were higher and other neutral amino acids lower in
HMZ mice compared with either HTZ or BTBR mice indicating a partial saturation of
the l-amino acid carrier at the blood brain barrier by the elevated plasma Phe
concentrations. In a series of steady-state experiments, the contribution of
leucine from the arterial plasma to the tRNA-bound pool in brain was found to be
statistically significantly reduced in HMZ mice compared with the other groups,
indicating that a greater fraction of leucine in the precursor pool for protein
synthesis is derived from protein degradation. We found reductions in lCPS(leu)
of about 20% throughout the brain in the HMZ mice compared with the other two
groups, but no reductions in brain concentrations of tRNA-bound neutral amino
acids. Our results in the mouse model suggest that in untreated phenylketonuria
in adults, the partial saturation of the l-amino acid transporter at the blood
brain barrier may not underlie a reduction in cerebral protein synthesis.
PMID- 11005873
TI - An approach to probe some neural systems interaction by functional MRI at neural
time scale down to milliseconds.
AB - In this paper, we demonstrate an approach by which some evoked neuronal events
can be probed by functional MRI (fMRI) signal with temporal resolution at the
time scale of tens of milliseconds. The approach is based on the close
relationship between neuronal electrical events and fMRI signal that is
experimentally demonstrated in concurrent fMRI and electroencephalographic (EEG)
studies conducted in a rat model with forepaw electrical stimulation. We observed
a refractory period of neuronal origin in a two-stimuli paradigm: the first
stimulation pulse suppressed the evoked activity in both EEG and fMRI signal
responding to the subsequent stimulus for a period of several hundred
milliseconds. When there was an apparent site-site interaction detected in the
evoked EEG signal induced by two stimuli that were primarily targeted to activate
two different sites in the brain, fMRI also displayed signal amplitude modulation
because of the interactive event. With visual stimulation using two short pulses
in the human brain, a similar refractory phenomenon was observed in activated
fMRI signals in the primary visual cortex. In addition, for interstimulus
intervals shorter than the known latency time of the evoked potential induced by
the first stimulus ( approximately 100 ms) in the primary visual cortex of the
human brain, the suppression was not present. Thus, by controlling the temporal
relation of input tasks, it is possible to study temporal evolution of certain
neural events at the time scale of their evoked electrical activity by
noninvasive fMRI methodology.
PMID- 11005874
TI - Prenatal stress produces learning deficits associated with an inhibition of
neurogenesis in the hippocampus.
AB - Early experiences such as prenatal stress significantly influence the development
of the brain and the organization of behavior. In particular, prenatal stress
impairs memory processes but the mechanism for this effect is not known.
Hippocampal granule neurons are generated throughout life and are involved in
hippocampal-dependent learning. Here, we report that prenatal stress in rats
induced lifespan reduction of neurogenesis in the dentate gyrus and produced
impairment in hippocampal-related spatial tasks. Prenatal stress blocked the
increase of learning-induced neurogenesis. These data strengthen
pathophysiological hypotheses that propose an early neurodevelopmental origin for
psychopathological vulnerabilities in aging.
PMID- 11005875
TI - Regional and strain-specific gene expression mapping in the adult mouse brain.
AB - To determine the genetic causes and molecular mechanisms responsible for
neurobehavioral differences in mice, we used highly parallel gene expression
profiling to detect genes that are differentially expressed between the 129SvEv
and C57BL/6 mouse strains at baseline and in response to seizure. In addition, we
identified genes that are differentially expressed in specific brain regions. We
found that approximately 1% of expressed genes are differentially expressed
between strains in at least one region of the brain and that the gene expression
response to seizure is significantly different between the two inbred strains.
The results lead to the identification of differences in gene expression that may
account for distinct phenotypes in inbred strains and the unique functions of
specific brain regions.
PMID- 11005877
TI - High phosphorylation efficiency and depression of uncoupled respiration in
mitochondria under hypoxia.
AB - Mitochondria are confronted with low oxygen levels in the microenvironment within
tissues; yet, isolated mitochondria are routinely studied under air-saturated
conditions that are effectively hyperoxic, increase oxidative stress, and may
impair mitochondrial function. Under hypoxia, on the other hand, respiration and
ATP supply are restricted. Under these conditions of oxygen limitation, any
compromise in the coupling of oxidative phosphorylation to oxygen consumption
could accentuate ATP depletion, leading to metabolic failure. To address this
issue, we have developed the approach of oxygen-injection microcalorimetry and
ADP-injection respirometry for evaluating mitochondrial function at limiting
oxygen supply. Whereas phosphorylation efficiency drops during ADP limitation at
high oxygen levels, we show here that oxidative phosphorylation is more efficient
at low oxygen than at air saturation, as indicated by higher ratios of ADP flux
to total oxygen flux at identical submaximal rates of ATP synthesis. At low
oxygen, the proton leak and uncoupled respiration are depressed, thus reducing
maintenance energy expenditure. This indicates the importance of low
intracellular oxygen levels in avoiding oxidative stress and protecting
bioenergetic efficiency.
PMID- 11005876
TI - Experimental diabetes in rats causes hippocampal dendritic and synaptic
reorganization and increased glucocorticoid reactivity to stress.
AB - We report that 9 d of uncontrolled experimental diabetes induced by
streptozotocin (STZ) in rats is an endogenous chronic stressor that produces
retraction and simplification of apical dendrites of hippocampal CA3 pyramidal
neurons, an effect also observed in nondiabetic rats after 21 d of repeated
restraint stress or chronic corticosterone (Cort) treatment. Diabetes also
induces morphological changes in the presynaptic mossy fiber terminals (MFT) that
form excitatory synaptic contacts with the proximal CA3 apical dendrites. One
effect, synaptic vesicle depletion, occurs in diabetes as well as after repeated
stress and Cort treatment. However, diabetes produced other MFT structural
changes that differ qualitatively and quantitatively from other treatments.
Furthermore, whereas 7 d of repeated stress was insufficient to produce dendritic
or synaptic remodeling in nondiabetic rats, it potentiated both dendritic atrophy
and MFT synaptic vesicle depletion in STZ rats. These changes occurred in concert
with adrenal hypertrophy and elevated basal Cort release as well as
hypersensitivity and defective shutoff of Cort secretion after stress. Thus, as
an endogenous stressor, STZ diabetes not only accelerates the effects of
exogenous stress to alter hippocampal morphology; it also produces structural
changes that overlap only partially with those produced by stress and Cort in the
nondiabetic state.
PMID- 11005878
TI - Reactivation of encoding-related brain activity during memory retrieval.
AB - Neuronal models predict that retrieval of specific event information reactivates
brain regions that were active during encoding of this information. Consistent
with this prediction, this positron-emission tomography study showed that
remembering that visual words had been paired with sounds at encoding activated
some of the auditory brain regions that were engaged during encoding. After word
sound encoding, activation of auditory brain regions was also observed during
visual word recognition when there was no demand to retrieve auditory
information. Collectively, these observations suggest that information about the
auditory components of multisensory event information is stored in auditory
responsive cortex and reactivated at retrieval, in keeping with classical ideas
about "redintegration, " that is, the power of part of an encoded stimulus
complex to evoke the whole experience.
PMID- 11005880
TI - Leadership: Challenges in the changing health care environment.
PMID- 11005881
TI - No-spill sippy cups.
PMID- 11005879
TI - Memory's echo: vivid remembering reactivates sensory-specific cortex.
AB - A fundamental question in human memory is how the brain represents sensory
specific information during the process of retrieval. One hypothesis is that
regions of sensory cortex are reactivated during retrieval of sensory-specific
information (1). Here we report findings from a study in which subjects learned a
set of picture and sound items and were then given a recall test during which
they vividly remembered the items while imaged by using event-related functional
MRI. Regions of visual and auditory cortex were activated differentially during
retrieval of pictures and sounds, respectively. Furthermore, the regions
activated during the recall test comprised a subset of those activated during a
separate perception task in which subjects actually viewed pictures and heard
sounds. Regions activated during the recall test were found to be represented
more in late than in early visual and auditory cortex. Therefore, results
indicate that retrieval of vivid visual and auditory information can be
associated with a reactivation of some of the same sensory regions that were
activated during perception of those items.
PMID- 11005882
TI - Primary health care for Hispanic children of migrant farm workers.
AB - Providing primary care to children of culturally diverse populations is a
challenge for pediatric nurse practitioners and educators. The challenge is
intensified when providing care to Hispanic children who are uprooted because
their parent(s) are migrant farm workers. The creation of health-focused academic
community partnerships is one unique strategy to improve primary care to these
children. One such partnership is the ongoing Migrant Family Health Program in
which practitioner nursing students and their faculty members provide primary
health care to children who are enrolled in a summer education program for
migrant children.
PMID- 11005883
TI - An added dimension to the pediatric health maintenance visit: the spiritual
history.
AB - The initial pediatric health maintenance visit gives the nurse practitioner (NP)
an opportunity to gather information about a family that can be used to devise an
effective and culturally sensitive plan of care. NPs have a history of exploring
spirituality as a segment of a family's culture to help children and their
parents cope with an acute or chronic illness. However, spirituality should also
be discussed with a family because it may affect their normal, everyday lives.
Religious traditions, values, and ethical concerns may provide rich insight into
a family's dynamic, which can increase an NP's understanding. The mnemonic B-E-L
I-E-F is used to guide NPs through a discussion of spirituality within a
pediatric health care maintenance context. This framework, which incorporates an
added dimension of spirituality into the health history, will further advance
efforts to assist families in fostering optimal childhood growth and development
during a routine health care maintenance visit.
PMID- 11005885
TI - Oral contraceptive pills: considerations for the adolescent patient.
AB - Combined oral contraceptive pills (OCPs) are the most commonly prescribed method
of birth control for adolescents. This article presents an overview of OCP
pharmacology and summarizes the different types of OCPs. The initial patient
evaluation and subsequent care are described, with a focus on management plans
specific to adolescents. Emergency contraception, an alternative use of OCPs, is
described as well. A thorough knowledge of OCPs and an appreciation of adolescent
specific management plans will enhance nurse practitioners' skills in preventing
pregnancy in their adolescent patients.
PMID- 11005884
TI - School-based support for urban adolescent mothers.
AB - INTRODUCTION: The purpose of this research was to examine infant birth weights
and high school completion rates for two cohorts of adolescent mothers attending
an urban school-based program, the Polly T. McCabe Center. METHOD: A
retrospective record review was conducted with two convenience samples of 47
adolescent mothers (study I) aged 16.1 +/- 1.4 years and 60 adolescent mothers
(study II) aged 15.9 +/- 1.4 years who were enrolled in the McCabe Center during
the 1992-1993 and 1996-1997 academic years. RESULTS: The incidence of low birth
weight infants born to students was 4% in study I and 13.6% in study II. High
school continuation/completion rates for study I were 79% at 3 years after
leaving the program and 80% for study II at 1 year after leaving the program.
DISCUSSION: The young mothers and infants appear to have benefitted from the
McCabe Center's intervention. Findings of the study suggest that continued
implementation of supportive school-based programs similar to the McCabe Center
may help prevent lower birth weight infants born to adolescent mothers and may
help decrease the high school drop-out rate among this population.
PMID- 11005886
TI - Perceptions of children with HIV infection when not told for so long:
implications for diagnosis disclosure.
AB - INTRODUCTION: The perceptions of school-aged children with HIV infection about
their illness were evaluated in light of parental/guardians communication about
the child's diagnosis to clarify guidelines for disclosure. METHOD: An
innovative, qualitative research design using methods of grounded theory and
projective drawings involved 12 children and 13 parents/guardians from a West
Coast Pediatric AIDS Clinical Trial treatment center. RESULTS: A specific process
of interaction between parents/guardians and children, when not told for so long,
emerged as the central phenomenon of the study. Parents/guardians kept the
children's HIV infection secret for 2 to 8 years after diagnosis. Regardless of
disclosure status, the children's drawings and conversations suggested severe
emotional distress, disturbed self-image, and social isolation. Parents and
guardians were unaware of their children's concerns. DISCUSSION: Although other
circumstances of the children's lives contributed to their poor psychosocial
adjustment, the long interval of silence about the illness also played a part in
their poor adjustment. Parents/guardians did not recognize when their children
needed more supportive information. Pediatric clinicians should therefore
continually assess children's psychosocial adjustment to guide families through
the disclosure process. The use of projective drawing techniques can facilitate
this process.
PMID- 11005887
TI - Neurofibromatosis: an elephant by another name.
PMID- 11005888
TI - Fluoride supplementation and caries prevention.
PMID- 11005889
TI - Case of a school-aged child with a limp and hip pain.
PMID- 11005890
TI - Politics set the agenda for children--and for pediatric nurse practitioners.
PMID- 11005891
TI - Getting ready for "the big talk" and beyond.
PMID- 11005892
TI - Questions & answers.
PMID- 11005894
TI - The Swiss Society for Prosthetic Dentistry-founded in 1980.
PMID- 11005893
TI - Indian Prosthodontic Society - founded in 1973.
PMID- 11005895
TI - Sectional collapsed denture for a partially edentulous patient with microstomia:
a clinical report.
PMID- 11005896
TI - Trial anterior artificial tooth arrangement for an immediate denture patient: a
clinical report.
PMID- 11005897
TI - Management of unfavorable implant placement: a clinical report.
PMID- 11005898
TI - Prosthodontic management of limited oral access after ablative tumor surgery: a
clinical report.
PMID- 11005899
TI - Corrosion-fatigue life of commercially pure titanium and Ti-6Al-4V alloys in
different storage environments.
AB - STATEMENT OF PROBLEM: Removable partial dentures are affected by fatigue because
of the cyclic mechanism of the masticatory system and frequent insertion and
removal. Titanium and its alloys have been used in the manufacture of denture
frameworks; however, preventive agents with fluorides are thought to attack
titanium alloy surfaces. PURPOSE: This study evaluated, compared, and analyzed
the corrosion-fatigue life of commercially pure titanium and Ti-6Al-4V alloy in
different storage environments. MATERIAL AND METHODS: For each metal, 33 dumbbell
rods, 2.3 mm in diameter at the central segment, were cast in the Rematitan
system. Corrosion-fatigue strength test was carried out through a universal
testing machine with a load 30% lower than the 0.2% offset yield strength and a
combined influence of different environments: in air at room temperature, with
synthetic saliva, and with fluoride synthetic saliva. After failure, the number
of cycles were recorded, and fracture surfaces were examined with an SEM.
RESULTS: ANOVA and Tukey's multiple comparison test indicated that Ti-6Al-4V
alloy achieved 21,269 cycles (SD = 8,355) against 19,157 cycles (SD = 3, 624) for
the commercially pure Ti. There were no significant differences between either
metal in the corrosion-fatigue life for dry specimens, but when the solutions
were present, the fatigue life was significantly reduced, probably because of the
production of corrosion pits caused by superficial reactions.
PMID- 11005900
TI - Differences in bonding to acid-etched or Er:YAG-laser-treated enamel and dentin
surfaces.
AB - STATEMENT OF PROBLEM: Er:YAG (erbium-doped yttrium aluminium garnet) lasers have
been effective in the removal of dental tissues. It has been suggested that they
are also useful for preparing dental surfaces for adhesion, but results to date
have been controversial. PURPOSE: This study compared the tensile strength of
bracket-tooth bonds obtained after preparation of the surface for adhesion
(dentin or enamel) by conventional acid-etching or by Er:YAG laser etching and
investigated microstructure of resin-tooth interfaces using the 2 procedures.
MATERIAL AND METHODS: Eighty healthy human premolars were used. Brackets were
cemented to acid-etched enamel, laser-etched enamel, acid-etched dentin, or laser
etched dentin (20 teeth per group). Dentin was previously exposed using a high
speed handpiece. Acid-etching was with 37% orthophosphoric acid (15 seconds for
enamel, 5 seconds for dentin). Laser etching was with Er:YAG laser (four 200 mJ
pulses per second for enamel; four 160 mJ pulses per second for dentin). Brackets
were bonded with autocuring resin paste, having first applied a primer (dentin
only) and then light-cured bonding resin. Tensile strength was determined with a
universal testing machine. Data were analyzed with 2-way ANOVA and subsequent t
test with Bonferroni correction. Fracture patterns were compared by the Wilcoxon
test with Bonferroni correction. For SEM studies of the resin-tooth interface, a
total of 12 premolars were used (3 for each tissue per treatment combination).
RESULTS: Mean tensile bond strength for acid-etched enamel (14.05 +/- 5.03 MPa)
was significantly higher (P<.05) than for laser-etched enamel (8.45 +/- 3.07
MPa), and significantly higher (P<.05) for acid-etched dentin (4.70 +/- 2.50 MPa)
than laser-etched dentin (2.48 +/- 1.94 MPa). Bond failure after laser etching
was due to microcohesive fracture of tooth tissue. SEM studies of both resin
enamel and resin-dentin interfaces indicated extensive subsurface fissuring after
laser etching. CONCLUSION: Adhesion to dental hard tissues after Er:YAG laser
etching is inferior to that obtained after conventional acid etching. Enamel and
dentin surfaces prepared by Er:YAG laser etching show extensive subsurface
fissuring that is unfavorable to adhesion.
PMID- 11005901
TI - Three-year clinical evaluation of direct and indirect composite restorations in
posterior teeth.
AB - STATEMENT OF THE PROBLEM: Objective long-term clinical data are necessary to
assess the performance of modern posterior composites as direct and indirect
restorations. PURPOSE: This prospective, long-term clinical trial evaluated
direct and indirect composite restorations for clinical acceptability as
posterior restoratives in single or multisurface cavities and provided a survey
on the 3-year results. MATERIAL AND METHODS: Under the supervision of an
experienced dentist, 9 dental students placed 88 composite restorations (Tetric,
blend-a-lux, Pertac-Hybrid Unifil), 43 direct composite restorations, and 45
indirect inlays. Clinical evaluation was performed at baseline and in yearly
intervals after placement by 2 other experienced dentists, using modified USPHS
criteria. A third follow-up of 60 restorations took place within 33 to 36 months
after placement. RESULTS: A total of 93% of indirect and 87% of direct
restorations were assessed to be clinically excellent or acceptable. During the
third year, 1 direct restoration in a molar failed because of margin opening.
Indirect inlays exhibited a significantly better anatomic form of the surface
than direct composite restorations. Premolars revealed a significantly better
marginal integrity and anatomic form of the surface than molars. Restorations in
molars exhibited a significantly higher failure rate compared with premolars.
CONCLUSION: Posterior composite restorations provided a satisfactory clinical
performance over a 3-year period, even if placed by relatively inexperienced but
supervised students.
PMID- 11005902
TI - Fracture resistance of Class II approximal slot restorations.
AB - STATEMENT OF PROBLEM: Determination of the fracture resistance of various
restorative materials in Class II approximal slot restorations has not been
studied. PURPOSE: This study evaluated the effects of retention grooves and
different restorative materials in Class II approximal slot restorations. To
explore the possibilities for further research, the probable effects of
preparation size and loading angle were investigated in a limited manner.
MATERIAL AND METHODS: Ninety sound, caries-free human maxillary premolars were
divided into 9 groups. The cavities were prepared either by hand or in a computer
controlled CNC machine with or without retention grooves. Four were restored with
adhesive amalgam, another 4 with composite, and a single group with Compomer
resin. The gingival floor depth was 1.5 mm. The specimens were loaded at an angle
of 13. 5 degrees to their longitudinal axes by using a computer-controlled
material testing machine until failure occurred. For one specific preparation of
adhesive amalgam, loading was applied at 0 and 30 degrees to determine the
probable effects of the loading angle. For a specific composite, resin
application, the effects of the change in gingival floor depth were analyzed by
assigning the depth to 2.0 mm. RESULTS: Composite and Compomer resin and
composite exhibited better performance than amalgam. The existence of the
retention grooves proved to be effective for adhesive amalgam restorations but
did not have any advantageous effect in composite and Compomer restoration.
CONCLUSION: For improved fracture resistance in small approximal restorations,
the use of composite was the appropriate choice. Compomer also gave satisfactory
results. Use of amalgam restoration should be accompanied with retention grooves
and an adhesive system to improve its performance.
PMID- 11005903
TI - Fracture resistance of posterior metal-free polymer crowns.
AB - STATEMENT OF PROBLEM: Improved mechanical properties of contemporary composites
has resulted in the extended use of composites for the restoration of posterior
teeth. Although the indication of polymers was extended to metal-free individual
crowns, the influence of tooth preparation design and cementation methods on the
stability of these artificial crowns remains unknown. PURPOSE: This in vitro
study evaluated the effect of axial tooth preparation design, occlusal dimension,
and cementation technique on the fracture resistance of metal-free posterior
Artglass crowns. MATERIAL AND METHODS: Seventy-two extracted human third molars,
assigned to experimental groups by size, received standardized tooth preparation.
Axial tooth preparation included an invasive approach with 1-mm deep shoulder and
a less invasive 0.5-mm chamfer preparation, whereas occlusal reduction was either
0.5 mm or 1.3 mm. Artglass crowns that restored the original tooth contour were
cemented with 3 cements: zinc phosphate cement (ZnP), glass ionomer cement (GIC),
or a resinous cement in combination with a dentinal bonding agent. After 10,000
thermal cycles between 5 degrees C and 55 degrees C, artificial crowns were
vertically loaded until compression to failure. Significant differences of
fracture loads between experimental groups were assessed by paired Mann-Whitney U
tests. RESULTS: Minimal fracture resistance for all combinations excluded 500 N.
However, 9 of 24 Artglass crowns cemented with ZnP loosened after thermocycling.
Adhesive cementation resulted in a significantly greater fracture resistance
compared with GIC and ZnP (P=.02). Increased occlusal thickness (0.5 to 1.3 mm)
resulted in greater stability, whereas a 1-mm deep shoulder tooth preparation did
not improve durability compared with a 0.5-mm chamfer finishing line. CONCLUSION:
A minimally invasive 0.5-mm axial chamfer tooth preparation combined with
sufficient occlusal reduction and adhesive cementation recorded the greatest
stability for posterior metal-free Artglass crowns.
PMID- 11005904
TI - Influence of metal surface finishing on porcelain porosity and beam failure loads
at the metal-ceramic interface.
AB - STATEMENT OF THE PROBLEM: Investigators suggest that metals should be finished in
1 direction before porcelain application to minimize metal irregularities and
trapped contaminants. These irregularities are thought to be focal points for
porosity and crack propagation. PURPOSE: This study investigated the influence of
metal finishing and sandblasting on (1) porosity production at the porcelain
metal interface, and (2) porcelain-metal beam failure load. MATERIAL AND METHODS:
Eighty cast metal samples were divided into 4 test groups: (A) bidirectional
finish/sandblasting; (B) unidirectional finish/sandblasting (C) bidirectional
finish only; and (D) unidirectional finish only. The porcelain applied was 1.5 mm
thick. Samples were sectioned longitudinally. Half of the samples were subjected
to a 3-point flexural test. The remaining samples were sectioned into 4 slices
and were examined with a light microscope (x500). Number and diameter of
porosities at the metal-porcelain interface were recorded. RESULTS: Mean loads at
failure (lbs) were as follows: A, 11.1 +/- 1.3 (5.03 +/- 0.58 Kg); B, 11.2 +/-
1.7 (5. 08 +/- 0.77 Kg); C, 4.0 +/- 1.8 (1.81 +/- 0.81 Kg); and D, 5.0 +/- 2. 1
(2.26 +/- 0.95 Kg). Groups A and B were significantly different from groups C and
D (P<.0001). Nonsandblasted samples (C and D) exhibited a separation at the
ceramometal interface, which prevented quantification of porosity size and
number. Average interface porosity sizes (microm) (A, 8.99 +/- 1.92; B, 10.03 +/-
1.86) showed no significant difference. The mean interface porosity number (A,
62. 3 +/- 16.02; B, 67.4 +/- 10.01) showed no significant difference. CONCLUSION:
Direction of metal finishing did not affect the porosity number and size at the
ceramometal interface or the beam failure loads. Sandblasting increased the beam
failure loads. Nonsandblasted samples showed detachment of the porcelain from the
metal.
PMID- 11005905
TI - Experimentally induced abutment strains in three types of single-molar implant
restorations.
AB - STATEMENT OF PROBLEM: The choice of single-molar implant design is difficult
because of a lack of controlled, quantitative biomechanical analyses. PURPOSE:
This study determined the effect of 3 single-molar implant designs on implant
strains under a variety of homologous loading conditions. MATERIAL AND METHODS:
On each implant abutment, 4 strain gauges were placed axially at 90 degrees to
each other on the buccal, lingual, mesial, and distal surfaces. Effects of
implant design, load location, direction, and magnitude were tested on axial and
bending (buccolingual and mesiodistal) strains of 3 single-molar implant designs:
(1) single, 3.75-mm (regular) diameter implant, (2) single, 5-mm (wide) diameter
implant, and (3) two 3.75-mm diameter (double) implants connected through a
single-molar crown. Results were analyzed with ANOVA. RESULTS: Variations in
loading conditions induced 3-dimensionally complex abutment strains on the tested
implant designs. Peak absolute strains in mesiodistal direction were 6493
microepsilon for design 1 and 3958 microepsilon on design 2, and 3160
microepsilon in buccolingual direction on design 3. For all loading conditions,
the single 3.75-mm diameter implant consistently experienced the largest strains
compared with wide-diameter and double implant designs. Changes in centric
contact location affected implant abutment strains differently among the 3
designs. Angulated force direction resulted in larger bending strains.
CONCLUSION: For single-molar implant designs, an increase in implant number and
diameter may effectively reduce experimental implant abutment strains.
PMID- 11005906
TI - Effect of anchorage systems and extension base contact on load transfer with
mandibular implant-retained overdentures.
AB - STATEMENT OF PROBLEM: Controversy exists regarding the effect of anchorage
systems and extension base contact on stress transfer to multiple implants by
mandibular overdentures. PURPOSE: This simulation study measured photoelastically
the biologic behavior of 4 implants retaining a mandibular overdenture. The
purpose of the investigation was to compare the load transfer characteristics of
different mandibular-retained overdenture designs, with and without edentulous
ridge contact. MATERIAL AND METHODS: A photoelastic model of a human edentulous
mandible was fabricated having 4 screw-type implants (3.75 x 10 mm) embedded in
the parasymphyseal area. Substructure designs utilizing a cantilevered bar, spark
erosion framework, noncantilevered bar, and solitary anchors were fabricated. A
vertical load of 30 lb was applied to the first molar unilaterally on each of the
4 standardized overdenture prostheses, with and without a silicone tissue spacer,
for a total of 8 tested conditions. Stresses that developed in the supporting
structure were monitored photoelastically and recorded photographically. RESULTS:
Without the simulated tissue contact on the posterior edentulous ridge, the
cantilevered bar framework caused the highest stresses to the terminal implant,
followed by spark erosion framework, non-cantilevered bar, and solitary anchor
design. With simulated tissue contact under the extension base, stress transfer
to the distal implant was uniformly reduced to a low level. CONCLUSION: Without
intimate extension base contact with the posterior edentulous ridge, the
cantilevered anchorage systems generated the highest stresses, under load, to the
ipsilateral terminal implant and the solitary anchor design transferred the
least. With simulated intimate extension base contact, all anchorage systems
transferred low stress to the distal implant region. For all conditions and
designs, low stress was transferred to the contralateral side of the arch.
PMID- 11005908
TI - Custom retainer for the Blom-Singer adjustable tracheostoma valve.
AB - This article presents a procedure that allows the laryngectomy patient to be
fitted with a well-sealed custom device. The custom device provides near-normal
speech during a variety of activities. The custom retainer for the Blom-Singer
adjustable tracheostoma valve can be fabricated with medical grade silicone using
routine prosthodontic techniques.
PMID- 11005907
TI - Effect of adhesive retention on maxillofacial prostheses. Part I: skin dressings
and solvent removers.
AB - STATEMENT OF PROBLEM: The success of most maxillofacial prostheses depends on
retention by medical adhesives. Products such as Smith-Nephew's Skin-Prep (SP)
are available that can be used on the skin that could improve prosthesis adhesion
protective dressing. The removal of adhesive from the skin is also problematic,
so solvents, such as Uni-Solve adhesive remover (US), are often used. PURPOSE:
This study measured the removal force of silicone elastomer strips with 2
adhesives from the skin of human subjects during the day, as affected by the use
of SP and US, and determined the site of adhesive failure. MATERIAL AND METHODS:
Silicone rubber strips were applied in a predetermined random order to the
ventral arm surfaces of 20 human subjects. US was applied to half the sites 1 day
before testing. SP was also applied to half the sites just before Epithane-3 (E3)
or Secure(2) Medical Adhesive (SMA) were used to adhere the strips. They were
peeled from the skin 6 hours later in an Instron at a rate of 10 cm/min. RESULTS:
A 3-way within-group MANOVA revealed significant differences without interactions
between adhesives (SMA=96.3 N.m, E3=24.1 N.m; P<.0005) and between use or nonuse
of SP (SP=65.8 N.m, no SP=54.6 N.m; P<.0005). The use of US was not significant
(no US=61.8 N.m, with US=58.6 N.m; P=.197). SMA adhered to the prostheses,
whereas E3 adhered to the skin, leaving a residue (Fisher exact test; P<.0003).
CONCLUSION: The combination of SMA and SP showed the highest adhesive bond
strength. Overall, SMA was 3 to 5 times more retentive than E3. SP improved
adhesion of both SMA (15%) and E3 (27%). SMA was still far more retentive. US had
no effect on retention. SMA remained on the prostheses, whereas E3 left a
difficult-to-remove residue on the skin.
PMID- 11005909
TI - Use of an ultrahigh-speed laser scanner for constructing three-dimensional shapes
of dentition and occlusion.
AB - STATEMENT OF PROBLEM: Acquisition of the 3-dimensional shape of dental casts is
useful for quantitative evaluation of the diagnosis and treatment of occlusion.
PURPOSE: This study demonstrated the acquisition of data through the use of an
ultrahigh-speed laser scanner and an originally developed goniometer, the use of
these tools to measure the entire 3-dimensional shape of the dental cast from
multiple directions, and the connection of the data measurements to reconstruct
the cast's occlusion with the use of a computer. MATERIAL AND METHODS: A
commercially available apparatus that emits a line laser and completes 1 scan in
only 0.6 seconds was used. To compensate for the unmeasured region, the cast was
measured from 4 directions on the original goniometer, and the connection of data
to obtain the entire image was carried out. Further, the reconstruction of the
occlusion between the upper and lower casts was attempted by transferring the
upper cast data to the lower cast. RESULTS: By the data connection, the entire
shape of the upper and lower casts was constructed, and the characteristic
structure was reproduced. The data connections were satisfactory for the flat
surfaces but less accurate for the inclined surfaces. Reconstruction of the
occlusion between the upper and lower casts was accomplished. It was then
possible to visualize the occlusion from arbitrary directions and sections with
computer graphics. CONCLUSION: The construction of the entire 3-dimensional shape
of a dental cast and the reconstruction of the occlusion were accomplished using
an ultrahigh-speed measurement system and original goniometer. These results will
be useful for clinical applications such as computerized diagnoses and treatment
of occlusion, and for the replacement of the stone casts in the dental office by
computerized data.
PMID- 11005910
TI - In vivo evaluation of the surface of posterior resin composite restorations: a
pilot study.
AB - STATEMENT OF PROBLEM: Several methods have been used to determine the surface
characteristics of resin composites in vivo and compare composite wear rates with
enamel wear rates. PURPOSE: This pilot study describes the surface
characteristics of resin composites and the wear of resin composites and enamel
during 1 year of in vivo service. MATERIAL AND METHODS: A single Class II
posterior resin composite restoration (Z100) was placed in 10 patients. Restored
teeth and unrestored adjacent control teeth were measured for wear 4 times within
the first year. A null point contact stylus profiler and fitting software were
used to measure epoxy casts. Maximum depth of wear, average depth of wear, and
characteristics of the restoration margin were determined. Paired t tests were
used to compare the control and restored teeth, and ANOVA was used to assess the
progression of wear over time (P<.05). RESULTS: After 1 year, maximum depth of
wear over the entire preparation region was on average 204.8 microm (+/- 129.8),
significantly greater than the 36. 8 microm (+/- 10.1) average maximum depth of
wear of enamel at occlusal contact areas on control teeth (P=.009). Maximum depth
of wear progressed over time (P=.009). Fracture of excess composite, commonly
called flash fracture, occurred in 50% of the restored teeth extending over the
preparation margin. CONCLUSION: Composite restorations wore significantly faster
than enamel contact areas on control teeth. Also of concern were the marginal
flash fractures that could facilitate secondary caries.
PMID- 11005911
TI - In vitro and in vivo corrosion evaluation of nickel-chromium- and copper-aluminum
based alloys.
AB - STATEMENT OF PROBLEM: The low resistance to corrosion is the major problem
related to the use of copper-aluminum alloys. PURPOSE: This in vitro and in vivo
study evaluated the corrosion of 2 copper-aluminum alloys (Cu-Al and Cu-Al-Zn)
compared with a nickel-chromium alloy. MATERIAL AND METHODS: For the in vitro
test, specimens were immersed in the following 3 corrosion solutions: artificial
saliva, 0.9% sodium chloride, and 1.0% sodium sulfide. For the in vivo test,
specimens were embedded in complete dentures, so that one surface was left
exposed. The 3 testing sites were (1) close to the oral mucosa (partial self
cleaning site), (2) surface exposed to the oral cavity (self-cleaning site), and
(3) specimen bottom surface exposed to the saliva by means of a tunnel-shaped
perforation (non-self-cleaning site). RESULTS: Almost no corrosion occurred with
the nickel-chromium alloy, for either the in vitro or in vivo test. On the other
hand, the 2 copper-aluminum-based alloys exhibited high corrosion in the sulfide
solution. These same alloys also underwent high corrosion in non-self-cleaning
sites for the in vivo test, although minimal attack was observed in self-cleaning
sites. CONCLUSION: The nickel-chromium alloy presented high resistance to
corrosion. Both copper-aluminum alloys showed considerable corrosion in the
sulfide solution and clinically in the non-self-cleaning site. However, in self
cleaning sites these 2 alloys did not show substantial corrosion.
PMID- 11005912
TI - Fabrication of an indirect-direct provisional fixed partial denture.
AB - This article describes a procedure for fabricating an optimal provisional
restoration before tooth preparation. The procedure involves the fabrication of
an indirect-direct provisional fixed partial denture. There are several
advantages to this procedure, such as reduced chair time, less heat generated in
the mouth, reduced contact between resin monomer and soft tissues, and optimal
esthetics.
PMID- 11005913
TI - Overdenture abutments for fixed partial dentures.
AB - Despite universal acceptance for retaining endodontically treated and filled
roots for vertical support of removable prostheses, there is little evidence for
the use of overdenture abutments with fixed prostheses. This article presents a
review of clinical situations for using these teeth to support fixed partial
dentures. These teeth provide vertical support during function and preserve
alveolar bone levels.
PMID- 11005914
TI - Simplified duplicating procedure for dental casts.
PMID- 11005915
TI - Simple technique for making custom impression trays.
PMID- 11005916
TI - Treatment outcomes of fixed or removable implant-supported prostheses in the
edentulous maxilla.
PMID- 11005917
TI - Reply
PMID- 11005918
TI - Transglycosylation by Streptococcus mutans GS-5 glucosyltransferase-D: acceptor
specificity and engineering of reaction conditions.
AB - The acceptor specificity of Streptococcus mutans GS-5 glucosyltransferase-D (GTF
D) was studied, particular the specificity toward non-saccharide compounds.
Dihydroxy aromatic compounds like catechol, 4-methylcatechol, and 3
methoxycatechol were glycosylated by GTF-D with a high efficiency.
Transglycosylation yields were 65%, 50%, and 75%, respectively, using 40 mM
acceptor and 200 mM sucrose as glucosyl donor. 3-Methoxylcatchol was also
glycosylated, though at a significantly lower rate. A number of other aromatic
compounds such as phenol, 2-hydroxybenzaldehyde, 1,3-dihydroxybenzene, and 1, 2
phenylethanediol were not glycosylated by GTF-D. Consequently GTF-D aromatic
acceptors appear to require two adjacent aromatic hydroxyl groups. In order to
facilitate the transglycosylation of less water-soluble acceptors the use of
various water miscible organic solvents (cosolvents) was studied. The flavonoid
catechin was used as a model acceptor. Bis-2-methoxyethyl ether (MEE) was
selected as a useful cosolvent. In the presence of 15% (v/v) MEE the specific
catechin transglucosylation activity was increased 4-fold due to a 12-fold
increase in catechin solubility. MEE (10-30% v/v) could also be used to allow the
transglycosylation of catechol, 4-methylcatechol, and 3-methoxycatechol at
concentrations (200 mM) otherwise inhibiting GTF-D transglycosylation activity.
PMID- 11005919
TI - Microbial sulfate reduction in a liquid-solid fluidized bed reactor.
AB - A liquid-solid fluidized bed reactor was used to carry out sulfate reduction with
a mixed culture of sulfate reducing bacteria. The bacteria were immobilized on
porous glass beads. Stable fluidized bed operation with these biofilm-coated
beads was possible. The low specific gravity of the hydrated beads allowed
operation at low liquid recirculation rates. H(2)S level in the reactor was
controlled by N(2) sparging, which also served as the location for liquid feed
and removal. Ethanol was used as the electron donor/carbon source for the
bacteria. Sulfate reduction rates up to 6.33 g sulfate L(-1) day(-1) were
attained in the reactor at a hydraulic retention time of 5.1 h. The effect of
hydraulic retention time and biomass loading on the beads, on reactor
performance, and efficiency were examined. The efficiency of sulfate reduction
increases considerably as the hydraulic retention increases, until the bacteria
became very strongly substrate-limited at 55h HRT. The effect of bead biomass
loading on bed expansion at various liquid superficial velocities was studied. A
model for the reactor was developed. Simulations of the continuous flow
experiments indicate that the model can describe the system well, and thus could
be used in the design/scale-up of such reactors. The model suggests that a
significant increase in the sulfate reduction capacity of the system is possible
by increasing the volume of the bed relative to the total liquid volume of the
system.
PMID- 11005920
TI - Studies related to the scale-up of high-cell-density E. coli fed-batch
fermentations using multiparameter flow cytometry: effect of a changing
microenvironment with respect to glucose and dissolved oxygen concentration.
AB - Multiparameter flow cytometric techniques developed in our laboratories have been
used for the "at-line" study of fed-batch bacterial fermentations. These
fermentations were done at two scales, production (20 m(3)) and bench (5 x 10(-3)
m(3)). In addition, at the bench scale, experiments were undertaken where the
difficulty of achieving good mixing (broth homogeneity), similar to that found at
the production scale, was simulated by using a two-compartment model. Flow
cytometric analysis of cells in broth samples, based on a dual-staining protocol,
has revealed, for the first time, that a progressive change in cell physiological
state generally occurs throughout the course of such fermentations. The technique
has demonstrated that a changing microenvironment with respect to substrate
concentration (glucose and dissolved oxygen tension [DOT]) has a profound effect
on cell physiology and hence on viable biomass yield. The relatively poorly mixed
conditions in the large-scale fermentor were found to lead to a low biomass
yield, but, surprisingly, were associated with a high cell viability (with
respect to cytoplasmic membrane permeability) throughout the fermentation. The
small-scale fermentation that most clearly mimicked the large-scale heterogeneity
(i.e., a region of high glucose concentration and low DOT analogous to a feed
zone) gave similar results. On the other hand, the small-scale well-mixed
fermentation gave the highest biomass yield, but again, surprisingly, the lowest
cell viability. The scaled-down simulations with high DOT throughout and locally
low or high glucose gave biomass and viabilities between. Reasons for these
results are examined in terms of environmental stress associated with an ever
increasing glucose limitation in the well-mixed case. On the other hand, at the
large scale, and to differing degrees in scale-down simulations, cells
periodically encounter regions of relatively higher glucose concentration.
PMID- 11005921
TI - Degradation of phenol and benzoic acid in a three-phase fluidized-bed reactor.
AB - Degradation of phenol and benzoic acid was studied in a fluidized-bed reactor
(liquid volume 2.17 L) under nonsterile conditions with special emphasis on
maximizing the flow through the reactor and investigating reactor performance at
fluctuating feeds. Reactor response to substrate pulses was investigated by
applying substrate square-wave inputs at a liquid flow of 1.00 L h(-1). A twofold
increase of the phenol and benzoic acid feed concentrations for 2.5 h did not
lead to accumulation and breakthrough. The cells were able to survive four to
fivefold increases of the feed concentration for 1 h without loss of viability,
although the phenol pulse lead to phenol accumulation in the reactor. Reactor
performance at constantly fluctuating loads was investigated by varying the feed
concentrations using sine wave functions. No accumulation of phenol or benzoic
acid was observed. Influence of induction was studied using shift experiments.
After 35 days of operation (369 hydrodynamic residence times) with phenol as sole
substrate (carbon source) the reactor was able to mineralize benzoic acid without
any adaptation or lag phase. The capability of phenol degradation, on the other
hand, was lost by most cells after only 3 days operation with benzoic acid as the
sole substrate. The experiments underline the importance of induction. In order
to maximize the flow through the reactor, the liquid flow was increased stepwise
while the feed concentrations were reduced correspondingly, keeping the
volumetric conversion rates of phenol (0.24 g L(-1) h(-1)) and benzoic acid (0.17
g L(-1) h(-1)) constant. By this means, liquid flow could be increased up to
13.32 L h(-1), which was more than 20-fold higher than the maximum liquid flow
achievable in a chemostat using the same conditions.
PMID- 11005922
TI - Degradation of organophosphorous nerve agents by enzyme-polymer nanocomposites:
efficient biocatalytic materials for personal protection and large-scale
detoxification.
AB - The biocatalytic destruction of organophosphates has become an important focus
area, as efficient "clean" technologies are sought for chemical weapons
decommissioning, counteracting nerve agent attacks, and protecting against
organophosphate pesticide poisoning. A novel method is advanced for immobilizing
the broad-spectrum enzyme organophosphorous hydrolase (OPH) from Pseudomonas
diminuta, based on the formation of nanocomposite protein-silicone polymers. The
resulting materials are highly active, stable, and versatile biocatalysts for the
liquid and gas phase detoxification of organophosphates, and can be fabricated as
monoliths, sheets, thick films, granulates, or macroporous foams. This approach
offers an efficient avenue to robust, high-performance biocatalytic OPH
containing polymers that outperform immobilized OPH catalysts reported to date.
The method provides for the first time a route to biocatalytic materials that may
be suitable for "active" protective wear, as well as bulk catalysts for the
destruction of large volumes of organophosphates. The preparation of OPH-silicone
biocomposites, their performances in the liquid and gas phase detoxification of
paraoxon, dichlorvos, and diisopropyl fluorophosphate, and their features are
discussed.
PMID- 11005923
TI - Enzymatic synthesis of oligosaccharides: product removal during a kinetically
controlled reaction.
AB - In this article, the enzymatic production of oligosaccharides, which is an
example of a kinetically controlled reaction, is studied. The aim is to show that
the product yield can be enhanced by continuous removal of oligosaccharides from
the reaction mixture. The oligosaccharides were removed by adsorption on
activated carbon. The absorption could be described by the multicomponent
Langmuir isotherm with different maximum saturation constants for mono-, di-, and
trisaccharides. The affinity for trisaccharides was larger (k(tri) = 3.52 l/g)
than for di- (k(di) = 0.94 l/g) and monosaccharides (k(mono) = 0.11 l/g). A model
combining kinetics, adsorption on activated carbon, and mass transfer in an
adsorption column was developed. Model calculations for the batch process with
removal showed a yield improvement of 23% compared to the batch process without
removal. Experimentally, a yield improvement of 30% was obtained. Model
calculations for the continuous process studied did not result in an increase of
the yield. The advantages of removal were masked by the negative influence of
recirculation and the relative large time between formation and removal.
PMID- 11005924
TI - Effect of insulin stimulation on the proliferation and death of Chinese hamster
ovary cells.
AB - The effect of environmental and genetic parameters on cell death was studied in
Chinese hamster ovary cell cultures. Experiments were performed using an
anchorage-dependent CHO cell line expressing gamma-IFN, and a second cell line
obtained by transfection of the previous one with bcl-2. In serum-free medium the
two cell lines showed a considerable degree of growth control entering quiescence
while maintaining high viabilities. The addition of transferrin did not have any
effect but insulin addition allowed cells arrested by serum withdrawal to reenter
the cell cycle. However, insulin supplementation also resulted in cell death,
which was possible to avoid through bcl-2 overexpression or in the presence of
serum. We propose that the expression of c-myc, shown to be induced by insulin,
plays an important role in the cell death observed after insulin addition in an
inappropriate environment, deficient in protective factors. This hypothesis is
supported by measurements of c-myc expression and cell cycle distribution.
PMID- 11005925
TI - Modeling substrate interactions during the biodegradation of mixtures of toluene
and phenol by Burkholderia species JS150.
AB - The biodegradation kinetics of toluene, phenol, and a mixture of toluene and
phenol by Burkholderia species JS150 was measured and modeled. Both of these
compounds can serve as the sole source of carbon and energy for this
microorganism. The single-substrate biodegradation kinetics was described well
using the Monod model, with model constants of mu(max,T) = 0.39 h(-1) and K(S,T)
= 0.011 mM for growth on toluene and mu(max,P) = 0.309 h(-1) and K(S,P) = 0.0054
mM for growth on phenol. Degradation of the mixture of toluene and phenol
followed simultaneous utilization kinetics with toluene being the preferred
substrate. Toluene was found to inhibit the rate of utilization of phenol while
the presence of phenol had little effect on the rate of degradation of toluene.
Of the kinetic models that were tested, one developed for microbial degradation
of multiple substrates was able to describe substrate interactions and to model
the mixture utilization by strain JS150. Simple competitive, noncompetitive, or
uncompetitive substrate kinetics were not sufficient to describe the observed
inhibitory interactions.
PMID- 11005926
TI - Use of 16S-rRNA to investigate microbial population dynamics during
biodegradation of toluene and phenol by a binary culture.
AB - Interspecies interactions and changes in the rate and extent of biodegradation in
mixed culture-mixed substrate studies were investigated. A binary mixed culture
of Pseudomonas putida F1 and Burkholderia sp. JS150 degraded toluene, phenol, and
their mixture. Both toluene and phenol can serve as sole sources of carbon and
energy for both P. putida F1 and strain JS150. To investigate the population
dynamics of this system, a fluorescent in-situ hybridization method was chosen
because of its ability to produce quantitative data, its low standard error, and
the ease of use of this method. When the binary mixed culture was grown on
toluene or phenol alone, significant interactions between the species were
observed. These interactions could not be explained by a pure-and-simple
competition model and were substrate dependent. Strain JS150 growth was slightly
inhibited when grown with P. putida F1 on phenol, and P. putida F1 grew more
rapidly than expected. Conversely, when the two species were grown together on
toluene alone, P. putida F1 was inhibited while strain JS150 was unaffected.
During growth of the mixed culture on a combination of toluene and phenol, the
interactions were similar to that observed during growth on phenol alone; P.
putida F1 growth was enhanced while strain JS150 was unaffected. Because of the
observed interspecies interactions, monoculture kinetic parameters were not
sufficient to describe the mixed culture kinetics in any experiment. This is one
of the first reports of microbial population dynamics in which molecular
microbial ecology and mathematical modeling have been combined. The use of the
16S-rRNA-based method allowed for observation and understanding of interspecies
interactions that were not observable with standard culture-based methods. These
results suggest the need for more investigations that account for both substrate
and microbial interactions when predicting the fate of organic pollutants in real
systems.
PMID- 11005927
TI - Error-prone PCR of Vitreoscilla hemoglobin (VHb) to support the growth of
microaerobic Escherichia coli.
AB - Expression of the gene encoding bacterial hemoglobin (VHb) from Vitreoscilla has
been previously used to improve recombinant cell growth and enhance product
formation under microaerobic conditions. It is very likely that the properties of
VHb are not optimized for foreign hosts; therefore, we used error-prone PCR to
generate a number of randomly mutated vhb genes to be expressed and studied in
Escherichia coli. In addition, the mutated VHb proteins also contained an
extension of eight residues (MTMITPSF) at the amino terminus. VHb mutants were
screened for improved growth properties under microaerobic conditions and 15
clones expressing mutated hemoglobin protein were selected for further
characterization and cultivated in a microaerobic bioreactor to analyze the
physiological effects of novel VHb proteins on cell growth. The expression of
four VHb mutants, carried by pVM20, pVM50, pVM104, and pVM134, were able to
enhance microaerobic growth of E. coli by approximately 22%, 155%, 50%, and 90%,
respectively, with a concomitant decrease of acetate excretion into the culture
medium. The vhb gene in pVM20 contains two mutations substituting residues
Glu19(A17) and Glu137(H23) to Gly. pVM50 expresses a VHb protein carrying two
mutations: His36(C1) to Arg36 and Gln66(E20) to Arg66. pVM104 and pVM134 express
VHb proteins carrying the mutations Ala56(E10) to Gly and Ile24(B5) to Thr,
respectively. Our experiments also indicate that the positive effects elicited by
mutant VHb-expression from pVM20 and pVM50 are linked to the peptide tail.
Removal of the N-terminal sequence reduced cell growth approximately 23% and 53%,
respectively, relative to wild-type controls. These results clearly demonstrate
that it is possible to obtain mutated VHb proteins with improved characteristics
for improving microaerobic growth of E. coli by using combined mutation
techniques, addition of a peptide tail, and random error-prone PCR.
PMID- 11005928
TI - Construction and structural modeling of a single-chain Fv-asparaginase fusion
protein resistant to proteolysis.
AB - In this study, we construct a fusion protein composed of L-asparaginase (ASNase;
from Escherichia coli AS 1.357) and a protective single-chain Fv (scFv), which
was selected from a phage-display scFv library from our previous studies. The
antibody moiety of the fusion protein was fused to the N-terminus of the enzyme
moiety via a linker peptide, (Gly(4)Ser)(6). Recombinant plasmid pET-SLA was
constructed to express scFv-ASNase fusion to high levels in E. coli and the
expressed product was found to form inclusion bodies. We obtained a soluble
fusion protein by refolding and purification. The soluble fusion protein
exhibited about 82% of the enzymatic activity of the native ASNase at the same
molar concentration, and had a K(m) value similar to that of the native enzyme
for the substrate L-asparagine. Importantly, the fusion protein was more stable
than native ASNase. In addition: (1) following treatment with trypsin, alpha
chymotrypsin, and rennet, at 37 degrees C for 30 min, scFv-ASNase fusion retained
94.0%, 88.8%, and 84.5% of its original activity, respectively, whereas native
ASNase became inactive; and (2) ScFv-ASNase fusion had a much longer in vitro
half-life (9 h) in serum than the native enzyme (2 h). The three-dimensional
structure of the fusion protein was obtained by modeling with the Homology and
Discover modules of the INSIGHT II software package. On the basis of the
structural evidence and biochemical properties, we propose that the scFv moiety
of the fusion protein may confer ASNase moiety resistance to proteolysis as a
result of both steric hindrance and a change in the electrostatic surface of the
enzyme.
PMID- 11005929
TI - High density cultivation of two strains of iron-oxidizing bacteria through
reduction of ferric iron by intermittent electrolysis.
AB - Electrolytic cultivation was applied to Leptospirillum ferrooxidans strains P3A
and CF27, which use ferrous iron to respire aerobically. Ferrous iron was
supplied to the bacteria by intermittent electrolytic reduction of ferric iron as
electron shuttle using an electrode. The yield of L. ferrooxidans and strain CF27
reached 20- and 50-fold, respectively, higher density than were achievable yields
without electrolysis. The time required to obtain high density depended not on
the growth ratio, but rather on the original growth rate of each strain.
PMID- 11005930
TI - The inhibition of Escherichia coli lac operon gene expression by antigene
oligonucleotides-mathematical modeling.
AB - Gene transcription is regulated by transcription factors that can bind to
specific regions on DNA. Antigene oligonucleotides (oligos) can bind to specific
regions on DNA and form a triplex with the double-stranded DNA. The triplex can
competitively inhibit the binding of transcription factors and, as a result,
transcription can be inhibited. A genetically structured model has been developed
to quantitatively describe the inhibition of the Escherichia coli lac operon gene
expression by triplex-forming oligos. The model predicts that the effect of
triplex-forming oligos on the lac operon gene expression depends on their target
sites. Oligonucleotides targeted to the operator are much more effective than
those targeted to other regulatory sites on the lac operon. In some cases, the
effect of oligo binding is similar to that of a mutation in the lac operon. The
model provides insight as to the specific binding site to be targeted to achieve
the most effective inhibition of gene expression. The model is also capable of
predicting the oligo concentration needed to inhibit gene expression, which is in
general agreement with results reported by other investigators.
PMID- 11005931
TI - All solid-state GFP sensor.
AB - An all-solid-state green fluorescent protein (GFP) sensor for GFP measurement was
developed. It is immune to interference from ambient light and works with
standard flow-through cuvettes. The sensor is practically insensitive to the
scattered excitation light encountered in microbial suspensions. It has a range
of 0.0002-1 g/L (7.4 x 10(-9) - 3.7 x 10(-5) M) with limit of detection 0.00019
g/L (7.0 x 10(-9) M). The sensor could be used with a UV or blue light emitting
diode (LED) as a light source, depending on required sensitivity, selectivity,
and background levels. Its very low cost makes it useful in a variety of
applications. This article describes the construction and validation of the
sensor both off- and on-line in fermentation processes.
PMID- 11005932
TI - Oral glycoprotein IIb/IIIa antagonists: new insights from the SYMPHONY trial.
AB - Platelet aggregation plays a central role in the pathophysiology of acute
coronary syndromes, and the platelet glycoprotein IIb/IIIa receptor has been
identified as the critical final mediator of this process. Antagonists of this
receptor used parenterally during both acute coronary syndromes and percutaneous
coronary interventions reduce the likelihood of subsequent major cardiac
complications. However, after the treatment period little further benefit
accrues. Based on these observations and that of the significant benefit of
aspirin in cardiovascular secondary prevention, oral glycoprotein IIb/IIIa
receptor antagonists are being evaluated with the goal of extending the benefit
of glycoprotein IIb/IIIa inhibition into chronic secondary prevention. This paper
will review the results of the SYMPHONY study of one such oral agent, sibrafiban,
and the current state of the oral glycoprotein IIb/IIIa inhibitor field.
PMID- 11005933
TI - Clopidogrel and coronary stenting: what is the next question?
AB - Today, following coronary stenting, clopidogrel has largely replaced ticlopidine
as part of combination antiplatelet therapy following coronary stenting primarily
due to its better tolerability. While there is no randomized, blinded, efficacy
trial of ticlopidine versus clopidogrel, there are ample data from a number of
observational studies, randomized non-blinded trials, and a randomized blinded
safety trial to prove that clopidogrel is not only safer than ticlopidine, but
also at least as efficacious following stenting. With over 10,000 treated
patients, pooled data suggest similar rates of stent thrombosis (clopidogrel
0.98% vs. ticlopidine 0.98%) and lower rates of major adverse cardiac events with
clopidogrel (clopidogrel 1.63% vs. ticlopidine 4.52%, p<0.001), with a clear
advantage for clopidogrel regarding adverse events (clopidogrel 5.91% vs.
ticlopidine 9.75%, p<0.001). With clopidogrel's superior safety and at least
equivalent efficacy, the question of "which thienopyridine?" post-stenting has
been answered. Now the questions "how much?", "how soon?" and "how long?" must be
addressed. The Clopidogrel for the Reduction of Events During Observation (CREDO)
trial is a multi-center, double-blind, randomized trial designed to answer these
remaining questions. CREDO will evaluate the efficacy and safety of clopidogrel
pretreatment versus no pretreatment, and prolonged (1 year), versus short-term (1
month) dual antiplatelet therapy in 2,000 patients undergoing planned or highly
probable coronary intervention with a stent.
PMID- 11005934
TI - A pharmacodynamic study of clopidogrel in chronic hemodialysis patients.
AB - Combination antiplatelet agents, particularly aspirin and ticlopidine, have found
increased use in the prevention of arterial thrombosis. Clopidogrel, a
thienopyridine derivative, like ticlopidine was recently approved by the U.S.
Food and Drug Administration (FDA) for the reduction of ischemic events in
patients with myocardial infarction, stroke, or peripheral arterial disease and
appears to have much less hematologic toxicity than ticlopidine has. Thrombosis
of hemodialysis access grafts is a major cause of morbidity in this patient
population. Combination antiplatelet agents may be particularly useful in the
prevention of hemodialysis access graft thrombosis. In preparation for such a
study, we have performed a pharmacodynamic study of the platelet inhibitory
effects of clopidogrel in patients on maintenance hemodialysis. Nine chronic
hemodialysis patients were studied. Baseline platelet aggregation studies were
performed, after which the subjects were begun on clopidogrel 75 mg daily.
Platelet aggregation studies were repeated after 14 days of therapy. Drug was
stopped and a final set of platelet aggregation studies were performed 7 days
later. Because clopidogrel acts by inhibiting adenosine diphosphate (ADP)-induced
platelet aggregation, we used ADP as the agonist in the platelet aggregation
studies. We also measured the time required to achieve hemostasis after removing
the dialysis needles at the termination of a dialysis session. Patients were
carefully monitored for any adverse reaction to clopidogrel. Fourteen days'
treatment with clopidogrel inhibited ADP-induced platelet aggregation from 48 to
23% with ADP 2 microM (P=0.0113), from 59 to 38% with ADP 5 microM (P=0. 0166),
and from 66 to 44% with ADP 10 microM (P=0. 0172). This inhibition of platelet
aggregation was reversed 7 days after stopping clopidogrel. Clopidogrel
administration did not affect the time required to achieve hemostasis after
removal of the dialysis needles. No adverse reactions were noted. No patient had
evidence of bleeding, rash or gastro-intestinal (GI) upset. Clopidogrel inhibits
ADP-induced platelet aggregation in subjects receiving chronic maintenance
hemodialysis. The magnitude of inhibition is similar to that reported in
nonuremic subjects with atherosclerosis. This inhibition is reversible within 7
days of discontinuing the drug. No adverse reactions to the drug were noted in
this short-term (14-day) trial.
PMID- 11005935
TI - Prevalence of early left ventricular thrombus after primary coronary intervention
for acute myocardial infarction.
AB - The prevalence of left ventricular (LV) thrombus after acute myocardial
infarction (AMI) has been reported high at 20-60%. Current reperfusion therapies
such as thrombolysis have shown a trend toward reducing the incidence of LV
thrombosis. However, the prevalence of LV thrombus after primary percutaneous
coronary intervention (PCI) for AMI has not been systematically studied. At
Massachusetts General Hospital 71 consecutive patients who underwent primary PCI
for acute ST elevation MI were reviewed for the prevalence of LV thrombus
evaluated by echocardiography. Echocardiography was performed within 5 days of
infarction. PCI was successful in all patients. The time delay from symptom onset
to intervention was 191 minutes. Thrombolysis in Myocardial Infarction (TIMI)
grade 3 flow was achieved in more than 80% of cases. Only 3 patients (4%) had
echocardiographic evidence of LV thrombus. All 3 patients had anterior
infarctions. The incidence among patients with anterior MI was 10% (3 of 30
patients). The prevalence of LV thrombus in patients treated with primary PCI for
AMI is low (4%).
PMID- 11005936
TI - The use of the electrocardiogram to identify epicardial coronary and tissue
reperfusion in acute myocardial infarction.
AB - The standard 12-lead electrocardiogram (ECG) gives us crucial information
concerning myocardial perfusion and the success of reperfusion therapy for ST
elevation acute myocardial infarction. Continuous monitoring has advantages over
repeated snapshot recordings. There are four electrocardiographic markers for
prediction of the perfusion status of the ischemic myocardium: (1) ST-segment
measurements, (2) T-wave configuration, (3) QRS changes, and (4) reperfusion
arrhythmias. Complete and stable (> or = 70%) resolution of ST-segment elevation
is associated with better outcome and preservation of left ventricular function
than partial (30 to 70%) or no (<30%) ST-segment resolution. Early inversion of
the T waves after initiation of reperfusion therapy is another marker of
myocardial reperfusion and a good prognostic sign. Using standard 12-lead ECG,
dynamic changes in Q-wave number, amplitude, and width; R-wave amplitude; and S
wave appearance are detected during reperfusion therapy. However, the
significance of these changes has not been clarified. Reperfusion arrhythmias,
especially bradycardia and accelerated idioventricular rhythm, are detected
occasionally during reperfusion therapy, but the value of reperfusion arrhythmias
as a marker of coronary artery patency is still debatable. Dynamic changes in the
QRS complexes, ST segments and T waves occur during reperfusion therapy and the
days after. Whereas changes in ST-segment amplitude have been extensively
studied, the significance of QRS-complex and T-wave changes is less clear, and
especially whether changes in the QRS complex and T wave may be complementary and
additive to ST-segment monitoring. It has remained unclear whether
electrocardiographic signs of reperfusion and reischemia should be used for
therapeutic decision making in the clinical setting.
PMID- 11005937
TI - Temporary reversal of anticoagulation using oral vitamin K.
AB - Brief reversal of oral anticoagulant therapy is frequently necessary prior to
minor surgery or invasive procedures. We sought to determine the effect of an
oral dose of 2.0 mg of vitamin K(1) on the international normalized ratio (INR)
among patients with a stable therapeutic INR who were maintained on their daily
dose of warfarin. We prospectively studied a convenience cohort of patients
attending an anticoagulation clinic who had either just completed treatment for
venous thromboembolism or were receiving prophylaxis for atrial fibrillation,
cardiomyopathy, or peripheral vascular disease. Each patient received an oral
dose of 2.0 mg of aqueous vitamin K(1). Serial INR measurements were taken over 1
week. There was wide variation in the INR response between patients, from no
change to complete reversal of anticoagulation. The effect also varied widely
over time. There was a significant inverse correlation between the fall in
logarithm of the INR and the daily warfarin dose required to achieve an INR value
of 2.5 (r=-0.52, p=0.011). Use of a 2.0 mg oral dose of vitamin K(1) does not
reliably reverse (correct) a therapeutic INR in patients maintained on their
daily dose of warfarin.
PMID- 11005939
TI - Epidemiology, diagnosis, and management of cardiac disease in chronic renal
disease.
AB - There is an extremely high burden of cardiovascular disease (CVD) in patients
with renal disease. Both traditional as well as uremia-related factors are
contributory. Diagnosis of CVD has limitations in patients with renal disease,
and suspicion for the presence of CVD needs to be high even in the absence of
classic symptoms. Prevention and management of CVD is similar to the general
population but important differences need to be noted.
PMID- 11005938
TI - Drug-induced thrombocytopenia in the coronary care unit.
AB - Drug-induced thrombocytopenia is a phenomenon that causes significant morbidity
and mortality among patients. Practitioners should be able to recognize the
clinical manifestations of drug-induced thrombocytopenia, differentiate it from
other causes, and manage it appropriately. Numerous case reports have documented
drug-induced causes of thrombocytopenia. The following article focuses on the
characteristics and management of drug-induced thrombocytopenia secondary to
medications commonly encountered in the coronary care unit. Pharmacotherapeutic
agents that are most commonly implicated in this setting include ticlopidine,
unfractioned heparin, glycoprotein (GP)IIb/IIIa inhibitors, H(2)-receptor
antagonists, quinidine and antibiotics. Case reports were obtained through a
comprehensive search of the Medicine database and subsequently complemented by
bibliographic reviews of the agents just specified. Reports that exhibited
possible, probable, and definite associations with drug-induced thrombocytopenia
are included in the article.
PMID- 11005940
TI - What is the required reperfusion period for assessment of myocardial infarct size
using triphenyltetrazolium chloride staining in the rat?
AB - Measurements of infarct size by use of tripenyltetrazoliumchloride (TTC) is a
widely accepted method used to delineate the extent of myocardial necrosis
following coronary occlusion and reperfusion in various animal experiments. There
is controversy, however, regarding the optimal reperfusion time for estimating
the maximally infarcted area by TTC staining in the rat. We tested six different
reperfusion times following 90 minutes of regional myocardial ischemia. Group 1
had 5 minutes of reperfusion (n=6), group 2 had 30 minutes of reperfusion (n=6),
group 3 had 1 hour of reperfusion (n=6), group 4 had 2 hours of reperfusion
(n=6), group 5 had 3 hours of reperfusion (n=6), group 6 had 4.5 hours of
reperfusion (n=6). Risk areas, measured by the use of blue dye, were similar
among the 6 study groups. Infarct size as a percent of risk area was 57+/-11% in
group 1, 74+/-7% in group 2, 61+/-9% in group 3, 71+/-5% in group 4, 70+/-5% in
group 5, and 64+/-9% in group 6 (x+/-standard error [SE]). There was no
significant difference in infarct size between the groups. However, prior to 60
minutes of reperfusion, patches of pink and white areas were observed within the
risk regions, indicating a more difficult assessment of proper delineation of
outer regions of necrotic tissue. For acute assessment of infarct size,
reperfusion for 60 minutes or more is optimal because the infarct does appear
homogeneous at that time and does not become larger with longer reperfusion
periods.
PMID- 11005942
TI - Effect of coronary thrombolysis on the plasma concentration of osteonectin
(SPARC, BM40) in patients with acute myocardial infarction.
AB - Osteonectin is a phosphoglycoprotein exclusively located in bone and platelet
alpha-granules. Human platelet-derived osteonectin is released into plasma after
thrombin-induced activation. Recognizing the unique distribution of the
osteonectin pool, we first sought to investigate whether osteonectin could serve
as a sensitive marker of platelet activity, and identify patients with acute
myocardial infarction (AMI). The second objective was to define the effects of
thrombolytic therapy in these patients on the plasma concentrations of
osteonectin at prespecified time points following attempted reperfusion.
Osteonectin levels by ELISA were determined in AMI patients before thrombolysis
and at 3, 6, 12, and 24 hours thereafter and compared with 12 healthy controls.
At baseline, soluble osteonectin plasma levels were similar between controls
(447. 7+/-20.6 ng/ml) and AMI patients (425.7+/-43.3 ng/mL; p=NS). A significant
increase of the soluble osteonectin was observed at 3 hours after thrombolysis
(519.4+/-26.9 ng/mL; p=0.03), and was followed by a decrease to baseline levels
at 6 hours after attempted reperfusion. Contrary to expectations, the plasma
osteonectin level in our pilot study was not a sensitive marker distinguishing
patients with AMI. The early peak of soluble osteonectin at 3 hours after
thrombolytic therapy is most likely not related to coronary thrombolysis per se
but rather to the phasic changes of platelet activity during myocardial ischemia
reperfusion. The unquestionable platelet origin of this protein and the lack of
elevated plasma levels of this alpha-granule constituent, challenge the postulate
of uniform platelet activation in AMI patients.
PMID- 11005941
TI - Combination of a direct thrombin inhibitor and a platelet glycoprotein IIb/IIIa
blocking peptide facilitates and maintains reperfusion of platelet-rich thrombus
with alteplase.
AB - We sought to determine the efficacy of the combination of argatroban, a direct
thrombin inhibitor, and G4120, a platelet glycoprotein (GP) IIb/IIIa blocker, to
enhance thrombolysis with alteplase. Platelet-rich thrombus in the rabbit
arterial thrombosis model is relatively resistant to alteplase despite the
addition of aspirin and heparin. The adjunctive use of either direct thrombin
inhibitors or GP IIb/IIIa inhibitors in thrombolysis has been investigated with
encouraging, but limited, success. The usefulness of combining both agents as
adjunctive therapy to thrombolysis has not been fully explored. Following
platelet-rich thrombus formation in the rabbit, argatroban (3 mg/kg), G4120 (0.5
mg/kg), G4120 plus heparin (200 U/kg), or G4120 plus argatroban were
intravenously infused over 60 minutes. Alteplase was given as intravenous boluses
(0.45 mg/kg) at 15-minute intervals up to 4 doses or until reperfusion. Blood
flow and bleeding time were monitored for 2 hours. The combination of G4120 plus
argatroban resulted in a persistent patency in 5 of 7 animals compared with 0 of
6 for argatroban alone (p=0.02), 1 of 6 for G4120 alone (p=0.08), and 2 of 6 for
G4120 plus heparin (p=0.2). Although during the infusion the bleeding times were
longer in the groups that received G4120 (26+/-7.7 minutes vs. 14+/-10 minutes,
p<0.05), by the end of the experiment there were no statistically significant
differences. Similarly, during the infusion the activated partial thromboplastin
times (aPTT) was higher in groups that received heparin or argatroban (99+/-51
seconds vs. 32+/-7.6 seconds, p<0.001), but by the end of the experiment the
aPTTs had returned to close to baseline in all groups except the G4120 plus
heparin group. These results suggest that lysis of platelet-rich thrombus with
alteplase requires the addition of both potent platelet and thrombin inhibitors.
Specifically designed agents, G4120 and argatroban, are effective without
additional increased risk for bleeding.
PMID- 11005943
TI - Changes in movement variables associated with transient overshoot of the final
position.
AB - Transient overshoot (TO), which is assessed as the distance between the movement
amplitude and the final position, was measured in a series of rapid, discrete
elbow flexion movements performed under different distance and loading conditions
by 7 participants. A positive relationship was found between kinematic variables
(peak velocity, peak acceleration and deceleration, and the symmetry ratio) and
the magnitude of TO, particularly in short movements performed against a light
load. The relationships between TO and electromyographic (EMG) variables were low
and mainly insignificant. Thus, TO contributes to the variability of rapid,
discrete movements and therefore should be taken into account as an additional
parameter in studies of the scaling of movement variables with movement
mechanical conditions. TO could also represent a consequence of mechanical
properties of the single-joint system rather than an independently programmed
primary submovement.
PMID- 11005944
TI - Developmental features of rapid aiming arm movements across the lifespan.
AB - Using a lifespan approach, the authors investigated developmental features of the
control of ballistic aiming arm movements by manipulating movement complexity,
response uncertainty, and the use of precues. Four different age groups of
participants (6- and 9-year-old boys and girls and 24- and 73-year-old men and
women, 20 participants in each age group) performed 7 types of rapid aiming arm
movements on the surface of a digitizer. Their movement characteristics such as
movement velocity, normalized jerk, relative timing, movement linearity, and
intersegment intervals were profiled. Analyses of variance with repeated measures
were conducted on age and task effects in varying movement complexity (Study 1),
response uncertainty (Study 2), and precue use (Study 3) conditions. Young
children and senior adults had slower, more variant, less smooth, and less linear
arm movements than older children and young adults. Increasing the number of
movement segments resulted in slower and more variant responses. Movement
accuracy demands or response uncertainty interacted with age so that the 6- and
74-year-old participants had poorer performances but responded similarly to the
varying treatments. Even though older children and young adults had better
performances than young children and senior adults, their arm movement
performance declined when response uncertainty increased. The analyses suggested
that young children's and senior adults' performances are poorer because less of
their movement is under central control, and they therefore use on-line
adjustments. In addition, older children and young adults use a valid precue more
effectively to prepare for subsequent movements than do young children and senior
adults, suggesting that older children and young adults are more capable of
organizing motor responses than are young children and senior adults.
PMID- 11005945
TI - Variability and noise in continuous force production.
AB - In the present 3 experiments, the authors examined the hypothesis, derived from
information theory, that increases in the variability of motor responses result
from increases in perceptual-motor noise. Three different groups of participants
(Ns = 10, 9, and 10, respectively, in Experiments 1, 2, and 3) produced
continuous isometric force under either low, intermediate, or high target force
levels. When considered together, the results showed that force variability (SD)
increased exponentially as a function of force level. However, an index of
information transmission (M/SD), as well as measures of noise in both the time
(approximate entropy) and the frequency (power spectrum) domains, changed
according to an inverted-U-shaped function over the range of force levels. The
findings provide further evidence that increased information transmission is
related to increases, and not to decreases, in the noisiness of the structure of
force output.
PMID- 11005946
TI - Performance and learning of generalized motor programs: relative (GMP) and
absolute (parameter) errors.
AB - The effects of practice (Experiment 1) and parameter variability (Experiment 2)
on the learning of generalized motor programs (GMPs) and movement
parameterization were investigated. In each experiment, 2 tasks with different
relative force-time structures were tested. Participants (N = 32, Experiment 1; N
= 40, Experiment 2) attempted to exert a pattern of force that resembled in force
and time a waveform that was displayed on a computer monitor. In both
experiments, the analysis suggested that the GMP, although refined over practice,
was relatively stable (i.e., resistant to decay and interference), even early in
practice (after 20 trials). In addition, the results indicated that constant and
variable parameter practice did not differentially affect GMP learning but did
degrade the learning of the parameter that was not varied. The data provided
additional evidence for the dissociation of the GMP and the parameterization
processes proposed in GMP theory. Contrary to schema theory, the present data
suggest an interdependence between the force and the time parameters: The
manipulation of 1 of the parameters has a negative effect on the learning of the
other parameter.
PMID- 11005947
TI - Bimanual finger tapping: effects of frequency and auditory information on timing
consistency and coordination.
AB - The authors' goal in this study was to probe the basis for an earlier, unexpected
finding that preferred-frequency finger tapping tends to have higher frequencies
and to be less stable for in-phase than for antiphase tasks. In follow-up
experiments, 3 protocols were employed: a preferred-frequency replication in both
coordination modes, a metronome-driven matching of the preferred frequencies to
each of the coordination modes, and a frequency scaling of both modes. The
original findings were affirmed for preferred frequency. Tapping to a metronome
had a differential effect on in-phase and antiphase: A more stable coupling
across frequencies was exhibited during in-phase. Under frequency scaling, the
antiphase pattern decomposed at lower frequencies than did in-phase, but no phase
transitions were observed. The loss of stable coordination in both modes was
attended by sudden increases in frequency differences between fingers and by
phase wandering. The emergence of those effects is discussed in light of
asymmetric modifications to the Haken-Kelso-Bunz model (H. Haken, J. A. S. Kelso,
& H. Bunz, 1985) and the task constraints of tapping.
PMID- 11005948
TI - Temporal precision in tapping and circle drawing movements at preferred rates is
not correlated: further evidence against timing as a general-purpose ability.
AB - Recently, researchers have discovered that individuals who are consistent timers
in a tapping task are not necessarily consistent timers when they perform a
continuous drawing task. In other words, nonsignificant correlations were found
among tapping and drawing movements for timing precision (S. D. Robertson et al.,
1999). In the present experiment, the authors investigated whether or not
consistency in timing for tapping and drawing was correlated when participants (N
= 24) were allowed to move at their preferred rate of movement. There were no
significant correlations between tapping and drawing in terms of timing
precision. That result lends further support to the notion that timing behavior
is specific to the nature of the task, and thus further weakens the idea that
timing is a generalized ability that can be imposed on a variety of different
types of tasks.
PMID- 11005949
TI - Adaptation of neuromuscular synergies during intentional constraints of space
time relationships in human gait.
AB - Tight frequency-to-amplitude relationships are observed in spontaneous human
steady gait. They can be modified, if required; that flexibility forms a
fundamental basis of the intentional adaptive capabilities of locomotion. In the
present experiments, the processes underlying that flexibility were investigated
at both the level of joint kinematics and the level of neuromuscular synergies.
Subjects (N = 4) walked at the same speed either with a preferred or a
nonpreferred frequency-to-amplitude relationship (i.e., constrained, short steps
at a high frequency [COS condition] or constrained, long steps at a low frequency
[COL condition]); their swing and stance phases were separately analyzed. In the
COS condition, increases in EMG activity were specifically required during the
swing phase. In the COL condition, several muscles required increases in EMG
activity during the stance phase, but decreases of the hamstring muscles were
needed during the swing phase. Whereas, in preferred walking, modification of the
frequency affects the EMG patterns globally (the gain increasing with the
frequency in both the stance and swing phases), the present results show that
changing the frequency in a constrained manner either affects the swing phase
specifically or affects both phases, but in the opposite direction. That finding
indicates that a separate control is needed in both the swing and the stance
phases.
PMID- 11005950
TI - Geometric phases for mixed states in interferometry.
AB - We provide a physical prescription based on interferometry for introducing the
total phase of a mixed state undergoing unitary evolution, which has been an
elusive concept in the past. We define the parallel transport condition that
provides a connection form for obtaining the geometric phase for mixed states.
The expression for the geometric phase for mixed state reduces to well known
formulas in the pure state case when a system undergoes noncyclic and unitary
quantum evolution.
PMID- 11005951
TI - Exact particle and kinetic-energy densities for one-dimensional confined gases of
noninteracting fermions.
AB - We propose a new method for the evaluation of the particle density and kinetic
pressure profiles in inhomogeneous one-dimensional systems of noninteracting
fermions, and apply it to harmonically confined systems of up to N = 1000
fermions. The method invokes a Green's function operator in coordinate space,
which is handled by techniques originally developed for the calculation of the
density of single-particle states from Green's functions in the energy domain. In
contrast to the Thomas-Fermi approximation, the exact profiles show negative
local pressure in the tails and a prominent shell structure which may become
accessible to observation in magnetically trapped gases of fermionic alkali
atoms.
PMID- 11005952
TI - Analytical results for the interaction energy of a trapped, weakly interacting
Bose-Einstein condensate.
AB - We examine the problem of a repulsive, weakly interacting and harmonically
trapped Bose-Einstein condensate under rotation. We derive a simple analytic
expression for the energy incorporating the interactions when the angular
momentum per particle is between zero and one and find that the interaction
energy decreases linearly as a function of the angular momentum in agreement with
previous numerical and limiting analytical studies.
PMID- 11005953
TI - Vortex precession in Bose-Einstein condensates: observations with filled and
empty cores.
AB - We have observed and characterized the dynamics of singly quantized vortices in
dilute-gas Bose-Einstein condensates. Our condensates are produced in a
superposition of two internal states of 87Rb, with one state supporting a vortex
and the other filling the vortex core. Subsequently, the state filling the core
can be partially or completely removed, reducing the radius of the core by as
much as a factor of 13, all the way down to its bare value of the healing length.
The corresponding superfluid rotation rates, evaluated at the core radius, vary
by a factor of 150, but the precession frequency of the vortex core about the
condensate axis changes by only a factor of 2.
PMID- 11005954
TI - Supercooling molecular hydrogen down through the superfluid transition.
AB - Recent calculations by Vorobev and Malyshenko [JETP Lett. 71, 39 (2000)] show
that molecular hydrogen may stay liquid and superfluid in strong electric fields
of the order of 4x10(7) V/cm. I demonstrate that strong local electric fields of
similar magnitude exist beneath a two-dimensional layer of electrons localized in
the image potential above the surface of solid hydrogen. Even stronger local
fields exist around charged particles (ions or electrons) if the surface or bulk
of a solid hydrogen crystal is statically charged. Measurements of the frequency
shift of the 1 --> 2 photoresonance transition in the spectrum of a two
dimensional layer of electrons above a positively or negatively charged solid
hydrogen surface performed in the temperature range 7-13.8 K support the
prediction of electric field induced surface melting. The range of surface charge
density necessary to stabilize the liquid phase of molecular hydrogen at the
temperature of superfluid transition is estimated.
PMID- 11005955
TI - Fracture and second-order phase transitions.
AB - Using the global fiber bundle model as a tractable scheme of progressive fracture
in heterogeneous materials, we define the branching ratio in avalanches as a
suitable order parameter to clarify the order of the phase transition occurring
at the collapse of the system. The model is analyzed using a probabilistic
approach suited to smooth fluctuations. The branching ratio shows a behavior
analogous to the magnetization in known magnetic systems with second-order phase
transitions. We obtain a universal critical exponent beta approximately = 0.5
independent of the probability distribution used to assign the strengths of
individual fibers.
PMID- 11005956
TI - Measurement of Newton's constant using a torsion balance with angular
acceleration feedback.
AB - We measured Newton's gravitational constant G using a new torsion balance method.
Our technique greatly reduces several sources of uncertainty compared to previous
measurements: (1) It is insensitive to anelastic torsion fiber properties; (2) a
flat plate pendulum minimizes the sensitivity due to the pendulum density
distribution; (3) continuous attractor rotation reduces background noise. We
obtain G = (6.674215+/-0.000092) x 10(-11) m3 kg(-1) s(-2); the Earth's mass is,
therefore, M = (5.972245+/-0.000082) x 10(24) kg and the Sun's mass is M =
(1.988435+/-0.000027) x 10(30) kg.
PMID- 11005957
TI - Fields over unsharp coordinates.
AB - It has been shown that space-time coordinates can exhibit only very few types of
short-distance structures, if described by linear operators: they can be
continuous, discrete, or "unsharp" in one of two ways. In the literature, various
quantum gravity models of space-time at short distances point towards one of
these two types of unsharpness. Here, we investigate the properties of fields
over such unsharp coordinates. We find that these fields are continuous--but
possess only a finite density of degrees of freedom, similar to fields on
lattices. As a special case we recover the Shannon sampling theorem of
information theory.
PMID- 11005958
TI - Search for lepton flavor violation in K+ decays into a charged pion and two
leptons.
AB - A search for lepton flavor violating decays, K+ --> mu+ mu+ pi-, K+ --> e+ e+ pi
, K+ --> pi+ e+ mu-, K+ --> mu+ e+ pi-, and pi0 --> e+ mu-, was performed using
the data collected in Experiment E865 at the Brookhaven Alternating Gradient
Synchrotron. No signal was found in any of the decay modes. At the 90% confidence
level, the branching ratios are less than 3.0x10(-9), 6.4x10(-10), 5. 2x10(-10),
5.0x10(-10), and 3.4x10(-9), respectively.
PMID- 11005961
TI - Dynamical symmetry breaking in the sea of the nucleon.
AB - We derive the nonanalytic chiral behavior of the flavor asymmetry d - u. Such
behavior is a unique characteristic of Goldstone boson loops in chiral theories,
including QCD, and establishes the unambiguous role played by the Goldstone boson
cloud in the sea of the proton. Generalizing the results to the SU(3) sector, we
show that strange chiral loops require that the s - s distribution be nonzero.
PMID- 11005959
TI - Study of charmless hadronic B meson decays to pseudoscalar-vector final states.
AB - We report results of searches for charmless hadronic B meson decays to
pseudoscalar( pi(+/-), K+/-, pi(0), or K(0)(S))-vector( rho, K(*), or omega)
final states. By using 9.7x10(6) BB pairs collected with the CLEO detector, we
report the first observation of B(-)--->pi(-)rho(0), B(0)-->pi(+/-)rho(-/+), and
B(-)-->pi(-)omega, which are expected to be dominated by hadronic b-->u
transitions. The measured branching fractions are (10.4(+3.3)(-3.4)+/-2.1)x10(
6), (27.6(+8.4)(-7.4)+/-4.2)x10(-6), and (11.3(+3.3)(-2.9)+/-1. 4)x10(-6),
respectively. Branching fraction upper limits are set for all of the other decay
modes investigated.
PMID- 11005964
TI - Chiral three-nucleon forces from p-wave pion production.
AB - Production of p-wave pions in nucleon-nucleon collisions is studied according to
an improved power counting that embodies the constraints of chiral symmetry.
Contributions from the first two nonvanishing orders are calculated. We find
reasonable convergence and agreement with data for a spin-triplet cross section
in pp-->pppi(0), with no free parameters. Agreement with existing data for a spin
singlet cross section in pp-->pnpi(+) constrains a short-range operator shown
recently to contribute significantly to the three-nucleon potential.
PMID- 11005965
TI - Shape of the 8B alpha and neutrino spectra.
AB - The beta-delayed alpha spectrum from the decay of 8B has been measured with a
setup that minimized systematic uncertainties that affected previous
measurements. Consequently the deduced neutrino spectrum presents much smaller
uncertainties than the previous recommendation [J. N. Bahcall et al., Phys. Rev.
C 54, 411 (1996)]. The 8B nu spectrum is found to be harder than previously
recommended with about (10-20)% more neutrinos at energies between 12-14 MeV. The
integrated cross sections of the 37Cl, 71Ga, 40Ar, and Super-Kamiokande detectors
are, respectively, 3.6%, 1.4%, 5.7%, and 2.1% larger than previously thought.
PMID- 11005966
TI - Giant resonances in the doubly magic nucleus 48Ca from the (e, e'n) reaction.
AB - The 48Ca(e,e(')n) reaction has been investigated for excitation energies 11-25
MeV and momentum transfers 0.22-0.43 fm(-1) at the superconducting Darmstadt
electron linear accelerator S-DALINAC. Electric dipole and quadrupole plus
monopole strength distributions are extracted from a multipole decomposition of
the spectra. Their fragmented structure is described by microscopic calculations
allowing for coupling of the basic particle-hole excitations to more complex
configurations. Comparison of the excitation spectrum of the residual nucleus
47Ca with statistical model calculations reveals a 39(5)% contribution of direct
decay to the damping of the giant dipole resonance.
PMID- 11005963
TI - Transverse asymmetry AT' from the quasielastic 3He(e,e') process and the neutron
magnetic form factor.
AB - We have measured the transverse asymmetry A(T') in 3He(e,e(')) quasielastic
scattering in Hall A at Jefferson Laboratory with high precision for Q2 values
from 0.1 to 0.6 (GeV/c)(2). The neutron magnetic form factor G(n)(M) was
extracted based on Faddeev calculations for Q2 = 0.1 and 0.2 (GeV/c)(2) with an
experimental uncertainty of less than 2%.
PMID- 11005962
TI - Three-pion interferometry results from central Pb+Pb collisions at 158A GeV/c.
AB - Three-particle correlations have been measured for identified pi(-) from central
158A GeV Pb+Pb collisions by the WA98 experiment at CERN. A substantial
contribution of the genuine three-body correlation has been found as expected for
a mainly chaotic and symmetric source.
PMID- 11005967
TI - Spectroscopy of double-beta and inverse-beta decays from 100Mo for neutrinos.
AB - Spectroscopic studies of two beta rays from 100Mo are shown to be of potential
interest for investigating both the Majorana nu mass by neutrinoless double beta
decay (0nubetabeta) and low energy solar nu's by inverse beta decay. With a
multiton 100Mo detector, coincidence studies of correlated betabeta from
0nubetabeta, together with the large Q value ( Q(betabeta)), permit
identification of the nu-mass term with a sensitivity of approximately 0.03 eV.
Correlation studies of the inverse beta decay and the successive beta decay of
100Tc, together with the large capture rates for low energy solar nu's, make it
possible to detect, in real time, individual low energy solar nu in the same
detector.
PMID- 11005968
TI - Surface plasmon dynamics in silver nanoparticles studied by femtosecond time
resolved photoemission.
AB - Multiphoton photoelectron spectroscopy reveals the multiple excitation of the
surface plasmon in silver nanoparticles on graphite. Resonant excitation of the
surface plasmon with 400 nm femtosecond radiation allows one to distinguish
between photoemission from the nanoparticles and the substrate. Two different
previously unobserved decay channels of the collective excitation have been
identified, namely, decay into one or several single-particle excitations.
PMID- 11005969
TI - Better schemes for quantum interrogation in lossy experiments.
AB - We show that several schemes exist for improving the efficiency of quantum
interrogations (or "interaction-free" measurements), which in principle are
limited by lossy experimental components. We show how one new scheme (the
"Helstrom" scheme) can efficiently detect the presence of a bomb which has been
designed to foil standard quantum interrogations by arming itself when there is
high probability of a photon being in the region. This particular new scheme can
probe a region of space with a greater probability of success than a person in
that region determining they are being probed.
PMID- 11005970
TI - Experimental real-time phase synchronization of a paced chaotic plasma discharge.
AB - Experimental phase synchronization of chaos in a plasma discharge is studied
using a phase variable lift technique (i.e., phase points separated by 2pi are
not considered as the same). Real-time observation of synchronized and
unsynchronized states is made possible through a real-time sampling procedure.
Parameter space regions of synchronization and unsynchronization are identified,
and a set of equations is suggested to model the real plasma circuit.
PMID- 11005971
TI - Negative refractive index in left-handed materials.
AB - The real part of the refractive index n(omega) of a nearly transparent and
passive medium is usually taken to have only positive values. Through an analysis
of a current source radiating into a 1D "left-handed" material (LHM)-where the
permittivity and permeability are simultaneously less than zero-we determine the
analytic structure of n(omega), demonstrating frequency regions where the sign of
Re[n(omega)] must, in fact, be negative. The regime of negative index, made
relevant by a recent demonstration of an effective LHM, leads to unusual
electromagnetic wave propagation and merits further exploration.
PMID- 11005972
TI - Pulsating, creeping, and erupting solitons in dissipative systems.
AB - We present three novel pulsating solutions of the cubic-quintic complex Ginzburg
Landau equation. They describe some complicated pulsating behavior of solitons in
dissipative systems. We study their main features and the regions of parameter
space where they exist.
PMID- 11005973
TI - Resonant formation and control of 2D symmetric vortex waves.
AB - It is shown that m-fold symmetric vortex waves in two dimensions ( V states)
preserve their functional form in a weak straining flow having appropriate
symmetry, but arbitrary time dependence. This phenomenon is used in driving the V
states into a highly nonlinear excitation by subjecting a circular vortex patch
to rotation and strain with oscillating strain rate and varying the rotation
angular velocity. The effect is due to autoresonance in the system as the excited
vortex state boundary self-adjusts its aspect ratio to synchronize with the
external flow.
PMID- 11005974
TI - Intense high-energy proton beams from Petawatt-laser irradiation of solids.
AB - An intense collimated beam of high-energy protons is emitted normal to the rear
surface of thin solid targets irradiated at 1 PW power and peak intensity
3x10(20) W cm(-2). Up to 48 J ( 12%) of the laser energy is transferred to
2x10(13) protons of energy >10 MeV. The energy spectrum exhibits a sharp high
energy cutoff as high as 58 MeV on the axis of the beam which decreases in energy
with increasing off axis angle. Proton induced nuclear processes have been
observed and used to characterize the beam.
PMID- 11005975
TI - Stabilization of neoclassical tearing modes by an externally applied static
helical field.
AB - The effect of a static helical magnetic field on the nonlinear growth of the
neoclassical tearing mode (NTM) is investigated. The NTM is found to be
stabilized by an externally applied helical field of a different helicity if the
field magnitude is sufficiently large, suggesting a very simple method for
stabilizing the NTM. The mechanism responsible for this stabilization is the
decreased fundamental harmonic pressure perturbation of the NTM in the presence
of the helical field.
PMID- 11005976
TI - Visualizing interfacial structure at non-common-atom heterojunctions with cross
sectional scanning tunneling microscopy.
AB - We describe how cross-sectional scanning tunneling microscopy (STM) may be used
to image the interfacial bonding across the nearly lattice-matched, non-common
atom GaSb/InAs heterojunction with atomic-scale precision. The method, which
takes advantage of the length difference between interfacial and bulk bonds,
appears equally applicable to AlSb/InAs and suggests how one might recover the
complete structure of either heterojunction from atomic-resolution STM data.
PMID- 11005977
TI - Shear instabilities of freely standing thermotropic smectic- A films.
AB - In this Letter we discuss theoretically the instabilities of thermotropic freely
standing smectic- A films under shear flow [3]. We show that, in Couette
geometry, the centrifugal force pushes the liquid crystal toward the outer
boundary and induces smectic layer dilation close to the outer boundary. Under
strong shear, this effect induces a layer buckling instability. The critical
shear rate is proportional to 1/sqrt[d], where d is the thickness of the film.
PMID- 11005978
TI - Pressure induces major changes in the nature of Americium's 5f electrons.
AB - Americium occupies a pivotal position in the actinide series with regard to the
behavior of 5f electrons. High-pressure techniques together with synchrotron
radiation have been used to determine the structural behavior up to 100 GPa. We
have resolved earlier controversial findings regarding americium and find that
our experimental results are in discord with recent theoretical predictions. We
have two new findings: (1) that there exists a critical, new structural link
between americium under pressure and its near neighbor, plutonium; and (2) that
the 5f electron delocalization in americium occurs in two rather than one step.
PMID- 11005960
TI - Measurement of J/psi and psi(2S) polarization in pp collisions at sqrt[s] = 1.8
TeV.
AB - We have measured the polarization of J/psi and psi(2S) mesons produced in pp
collisions at sqrt[s] = 1.8 TeV, using data collected at the Collider Detector at
Fermilab during 1992-1995. The polarization of promptly produced J/psi [psi(2S)]
mesons is isolated from those produced in B-hadron decay, and measured over the
kinematic range 4 [5.5]
axis. The 1794-cm(-1) line is assigned to bond center H in the
positive charge state, whereas the 745-cm(-1) line is ascribed to negatively
charged H located on a <111> axis close to the tetrahedral site.
PMID- 11005980
TI - Effect of inelastic deformation on crystallite size in post-shock 6H polytype
SiC.
AB - Shock-recovery experiments have been conducted on 6H polytype silicon carbide to
135 GPa and post-shock samples have been analyzed by Raman spectroscopy, x-ray
diffraction, and electron microscopy. Results indicate that at up to 25-30 GPa,
crystallite size is reduced faster than above this pressure, when reduction
slows. Shock-induced inelastic deformation of 6H-SiC is known to develop fully
for stress above 25 GPa, coinciding with the pressure range observed where
crystallite size reduction decreases. Inelastic deformation appears to be
responsible for this slowed crystallite size reduction.
PMID- 11005981
TI - Four regimes of decaying grid turbulence in a finite channel.
AB - Attenuation of second sound in helium II has been used to observe up to 6 orders
of magnitude of decaying vorticity displaying four distinctly different regimes
of decaying grid turbulence in a finite channel. A purely classical spectral
model for homogeneous and isotropic turbulence describes most of the decay of
helium II vorticity in the temperature range 1.2/=31 (chi(2) trend =
10.1). Breast-feeding for more than 1 year was associated with an OR of 0.5 (95%
CI, 0.4-0.8). Forty-two (9.5%) cases and 164 (18.9%) controls reported ever oral
contraceptive use: in comparison with never users, the multivariate OR was 0.4
(95% CI 0.3-0.6) for ever users, and the risk decreased with duration of use. The
OR for ovarian cancer was 2.9 (95% CI, 1.5-5.8) for women with a family history
of the disease. CONCLUSION: This study, conducted on a relatively low-risk
population, confirms the role of oral contraceptive on ovarian cancer risk and
the direct association with family history of ovarian cancer. It also indicates
that a later age at first birth is directly, and induced abortion and breast
feeding are inversely, related to the risk of the disease.
PMID- 11006031
TI - Retrograde seeding of malignant cells during hysteroscopy in presumed early
endometrial cancer.
AB - OBJECTIVE: The aim of this study was to determine the effect that preoperative
hysteroscopy has on the frequency of positive cytology at the time of definitive
surgical management in endometrial cancer. METHODS: Charts of 222 patients with
endometrial cancer were reviewed. Patients were divided according to whether (n =
64) or not (n = 158) they had hysteroscopy with saline infusion. Each group was
stratified into low or high risk for positive peritoneal cytology. Logistic
regression analysis was used to compare the prevalence of positive peritoneal
cytology with and without hysteroscopy, before and after the stratification,
adjusting for the confounding risk factors. RESULTS: After adjusting for
confounding variables there was a statistical difference in the frequency of
positive peritoneal cytology in those who had hysteroscopy versus those who did
not (odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.02-6.63, P = 0.05).
Even after stratifying patients into a low-risk group (OR = 2.12, 95% CI = 0.13
35.9, P = 0.6) and a high-risk group (OR = 3.46, 95% CI = 1.3-9.12, P = 0.01) the
difference in the high-risk group was statistically significant. CONCLUSION:
Hysteroscopy seems to affect the prevalence of positive peritoneal cytology,
especially in those patients with high-risk cell types. Its use in patients with
suspicion of endometrial cancer should be reconsidered.
PMID- 11006032
TI - Combined laparoscopic and vaginal radical surgery in cervical cancer.
AB - OBJECTIVE: The purpose of our study was to review our experience with
laparoscopic staging and vaginal radical surgery in the treatment of early stage
cervical cancer. STUDY DESIGN: We reviewed the charts of 102 patients who had a
laparoscopic pelvic lymphadenectomy followed by vaginal radical hysterectomy
(VRH) or vaginal radical trachelectomy (VRT). RESULTS: Patients' age ranged from
25 to 68 years (median: 36). Squamous and adenocarcinoma histology occurred in 68
and 32%, respectively. Stage Ib1 occurred in 77% of cases and the rest were stage
Ia1 (1%), 1a2 (16%), and IIa (6%). Patients were divided into three groups: VRH
(57), VRT (34), and node only (NO) (11), when positive nodes were identified on
frozen section. Median operative time for VRH and VRT were 270 and 260 min
compared to 200 min in the NO group (half also had bilateral paraaortic node
dissection, which lengthened the OR time). Hospital stay was shorter in the NO
group (2 days). For each group (VRH, VRT, and NO) the median pelvic node count
was 27, 26, and 23 and the median paraaortic node count was 3, 4, and 9. Two VRH
were converted to an abdominal procedure because of technical difficulties and
one VRT was converted to a VRH because of positive endocervical margins.
Intraoperative complications related to laparoscopy included two iliac and one
epigastric vessel injuries. Complications related to the radical surgeries
included three cystostomies, managed vaginally, and a laparotomy for parametrial
bleeding after VRT. Postoperative complications occurred in 6% of patients and
only one was considered major (an abscess which required surgical drainage).
Overall, there were only four recurrences in the vaginal surgery groups and one
in the NO group. There were no ureteral or intestinal injuries and there have
been no trocar site recurrences. CONCLUSION: Our data show that approaching
cervical cancer with a combined laparoscopic and vaginal surgery is feasible. The
overall morbidity and complication rate are low and the lymph node count is
satisfactory. Staging the nodes laparoscopically first to identify positive nodes
is advantageous, particularly since we favor the use of chemoradiation therapy in
those cases. The laparoscopic node staging thus avoids an unnecessary laparotomy
in patients with positive nodes, reduces morbidity, and allows for early
radiation therapy.
PMID- 11006033
TI - Cisplatin and pentoxifylline in advanced or recurrent squamous cell carcinoma of
the cervix: a phase II trial of the Gynecologic Oncology Group.
AB - OBJECTIVE: The aim of this study was to determine the antitumor activity and
toxicity of cisplatin and pentoxifylline in previously treated patients with
squamous cell carcinoma of the cervix. METHODS: A Gynecologic Oncology Group
(GOG) Phase II trial of recurrent squamous cell cervical cancer using standard
GOG response and toxicity criteria was performed. RESULTS: A total of 47 patients
with advanced or recurrent squamous cell carcinoma of the cervix were entered.
The starting dose was 75 mg/m(2) of cisplatin every 21 days and 1600 mg of
pentoxifylline PO every 8 h for nine doses during each course. Forty patients
were evaluable for response and 44 were evaluable for toxicity. Of the 40
evaluable patients, 37 had received prior radiotherapy and 35 had received prior
chemotherapy. A median of three courses were given (range: 1-7). Among evaluable
patients, 1 had a complete response (2.5%) and 3 had a partial response (7.5%)
for an overall objective response rate of 10%. The complete responder had not
previously had chemotherapy. Grade 3 or 4 toxicity was predominantly nausea and
vomiting (32%) and hematologic toxicity (23%). CONCLUSIONS: The combination of
cisplatin and pentoxifylline at the dose and schedule tested has limited activity
in previously treated advanced or recurrent cervical cancer.
PMID- 11006034
TI - Constitutive activation of stat 3 oncogene product in human ovarian carcinoma
cells.
AB - OBJECTIVE: Stat 3 functions in transducing signals from the cell's surface to its
nucleus and activation of gene transcription. Aberrations of Stat 3 in breast
cancer have raised the possibility of its contribution to oncogenesis. Our goal
was to examine ovarian cancer cell lines to determine whether Stat 3 plays a
relevant role in ovarian carcinogenesis. METHODS: Protein lysates were extracted
from normal ovarian surface epithelial cells and malignant cells. Western
blotting techniques were performed with phosphorylation-independent or
phosphorylation-specific Stat 3 (tyrosine 705) antibody. Confirmation of Stat 3
activation was determined by a luciferase reporter driven by a promoter
containing Stat 3-specific binding sites. Bcl-x(L) and cyclin D(1) were also
analyzed by Western blotting. RESULTS: MDAH 2774, OV-1063, Caov-3, and O.C. 22819
expressed high levels of phosphorylated Stat 3. In contrast, A2780 and normal
ovarian surface epithelial cells had little Stat 3 phosphorylation recognized.
Confirmation of persistent activation of Stat 3 activity was shown by
transfection of cells with a Stat 3 luciferase reporter. Potential downstream
mediators of Stat 3 including Bcl-x(L) and cyclin D(1) were also evaluated. In
cells expressing activated Stat 3, high levels of both Bcl-x(L) and cyclin D(1)
were detected, whereas in A2780 cells, which did not express activated Stat 3,
only low levels of Bcl-x(L) and cyclin D(1) were expressed. CONCLUSIONS:
Constitutive activation of Stat 3 is present in ovarian cancer lines but not in
normal ovarian surface epithelial cells. Activation of Stat 3 is a common event
during oncogenic transformation upstream to both Bcl-x(L) and cyclin D(1). The
relationship of this aberrancy of ovarian carcinoma harboring activated Stat 3
deserves further investigation.
PMID- 11006035
TI - Patients with double primary tumors in the breast and ovary- clinical
characteristics and BRCA1-2 mutations status.
AB - OBJECTIVE: The aim of this study was to define the prevalence, clinical
characteristics, and BRCA1-2 mutation carrier status of ovarian cancer (OvC)
patients with a previous primary malignancy in the breast (PPMBr). METHODS: The
study population comprised 1240 consecutive Jewish Israeli women with
pathologically confirmed epithelial OvC diagnosed between March 1, 1994, and
December 31, 1997. Demographic and clinical data were obtained from medical files
and from a detailed questionnaire taken through a nationwide epidemiological case
control study on OvC. Blood samples and tumor tissues were collected for analysis
of the three predominant germline BRCA1-2 Jewish founder mutations (185delAG,
5382insC, and 6174delT). RESULTS: Fifty nine (4.7%) patients with OvC had a
PPMBr. The median age at diagnosis of OvC was 60 years. The mean interval between
the two diagnoses was 104 months (range 0-363 months). In the majority of the
patients (n = 53), the diagnosis of breast cancer (BrC) preceded the OvC by more
than 1 year. The ovarian tumors were diagnosed in 47% of the cases following
investigation of patients' symptoms. In 41%, diagnosis was made as a consequence
of check-up exams performed during the routine follow-up of BrC survivors.
Patients with PPMBr were more likely to present with FIGO ovarian stage III-IV,
compared to women with solitary OvC (73% vs 60. 3%, P < 0.05), and less likely to
have borderline tumors (3.4% vs 17. 9%, P = 0.007). Family history of OvC/BrC was
recorded in 26% of this group of patients compared to 10.5% among patients with
solitary OvC (P = 0.003). Patients with PPMBr had an exceptionally high
prevalence of BRCA1-2 mutations (57%), irrespective of family history.
CONCLUSIONS: Patients with PPMBr present with more advanced disease and invasive
type epithelial ovarian tumors when compared to cases associated with solitary
OvC. The rate of BRCA1-2 mutations in Jewish women with OvC who had PPMBr is at
least twice as high as in Jewish women with OvC as the solitary disease.
PMID- 11006036
TI - Age as a prognostic factor for recurrence in patients with endometrial carcinoma.
AB - PURPOSE: The aim of this study was to evaluate age as a prognostic factor for
recurrence in endometrial cancer patients treated with primary surgery. METHODS:
Between 1983 and 1998, 455 endometrial cancer patients underwent primary surgery
at our institution. Patients were divided into three age groups based on age at
diagnosis: Group A (age <60, n = 156), B (age 60-69, n = 147), and C (age >/=70,
n = 152). Clinicopathologic, treatment factors, and outcome were compared among
the three groups. Prognostic factors were evaluated by univariate and
multivariate analysis. RESULTS: The three age groups had a similar distribution
of most pathologic features including stage, histology, cervical involvement,
positive cytology, adnexal involvement, nodal metastases, serosal involvement,
and lymphovascular invasion (LVI). Older women had a higher rate, however, of
deep (>1/2) myometrial invasion (P < 0.0001) and grade 3 tumors (P < 0.0001). The
extent of surgical staging and use of adjuvant radiation therapy were similar.
Five-year disease-free survivals (DFS) of Groups A, B, and C were 74.3, 70.2, and
60.3%, respectively (P = 0.08). A significant difference in DFS was seen when
Groups A and B were combined and compared with Group C (72.0 vs 60.3%, P = 0.03).
Multivariate analysis confirmed the significance of race, stage, grade, and LVI.
Age was not found to be associated with recurrence (HR 1.1, 95% C.I. 0.91-1.5, P
= 0.21). CONCLUSION: Our results reveal that, in a large cohort of comparably
staged and treated endometrial carcinoma patients, age is not a prognostic factor
for recurrence.
PMID- 11006037
TI - Age-specific survival of women with endometrioid adenocarcinoma of the uterus.
AB - OBJECTIVE: The purpose of this paper was to evaluate the age-specific survival
for women diagnosed with endometrioid adenocarcinoma of the uterus. METHODS: A
retrospective analysis was conducted of 328 patients diagnosed with endometrioid
adenocarcinoma of the uterus between January 1990 and December 1997. Patients
were followed for 3 to 96 months with a mean of 43 months. The impact of age on
survival was assessed using Cox proportional hazard regression and multivariate
analysis for age, stage, and grade. Stage and grade were analyzed using log-rank
tests, and survival curves were generated by the Kaplan-Meier method. RESULTS: A
total of 328 patients were evaluated. Multivariate analysis revealed age, stage,
and grade were all significant independent predictors of survival (P < 0.0001).
Age-specific survival varied from a high of 90% at age 40 to a low of 55% at age
80. Interval age-specific survival decreased below 86% at age 50. Subset analysis
of patients younger than 50 compared with older patients revealed no difference
in surgical stage or grade of tumors among these patients. Patients older than
50, however, were 41% more likely to receive adjuvant radiation therapy.
CONCLUSION: Age is a specific, significant predictor of outcome in endometrioid
adenocarcinoma of the uterus. Survival decreases significantly in patients older
than 50. This decreased survival associated with age is unrelated to surgical
stage or grade of adenocarcinoma. Decreased survival could involve molecular
differences in the developing endometrial cancer or an increased risk of death
from other non-cancer-related factors.
PMID- 11006038
TI - Chromosome 4 deletions are frequent in invasive cervical cancer and differ
between histologic variants.
AB - OBJECTIVE: Patterns of discontinuous deletion of chromosome 4 have been described
in histologic variants of lung carcinomas and may represent different "hotspot"
targets for gene-environment interactions. Since similar environmental risks
exist for cervical cancer, we investigated patterns of discontinuous deletion in
two major histologic variants. METHODS: Thirteen archival cases of squamous cell
cancer (SCCA) and 11 cases of adenocarcinoma (AC) were precisely microdissected.
Matched normal and tumor DNA were used for polymerase chain reaction (PCR) based
loss of heterozygosity (LOH) analyses using 19 polymorphic markers spanning
chromosome 4. Human papillomavirus (HPV) detection was determined by PCR using
general and type-specific primers (HPV 16, 18). Differences in LOH between
histologic tumor types and chromosomal regions were determined using Fisher's
exact test. RESULTS: Loss at any chromosome 4 locus occurred in 92% of all tumors
studied, with the majority of deletions occurring on the long arm of the
chromosome. Four discrete minimal regions of discontinuous deletion (R) were
identified. For these regions, LOH frequencies were 76% (R1, 4q34-q35), 48% (R2,
4q25-q26), 36% (R3, 4p15.1-p15.3), and 26% (R4, 4p16). Loss in SCCA predominated
at 4q (4q34-q35; 83%) and in AC at 4p (4p15.3; 50%). Overall LOH on the p arm was
significant in AC (82%) compared to SCCA (31%) (P = 0.02). HPV detection was
similar in SCCA (85%) and AC (73%), and HPV 16/18 subtypes were similarly
represented in both histologies. CONCLUSIONS: Chromosome 4 deletions are frequent
in cervical carcinomas. Different patterns of deletion between SCCA and AC may
represent gene regions targeted by different gene-environment interactions in
these tumor subtypes.
PMID- 11006039
TI - Cisplatin-paclitaxel-cyclophosphamide with G-CSF in primary advanced epithelial
ovarian cancer.
AB - INTRODUCTION: In an attempt to increase survival, we performed a prospective
trial of high-dose cisplatin-paclitaxel-cyclophosphamide with granulocyte colony
stimulating factor (G-CSF) for three cycles followed by carboplatin-paclitaxel
for three cycles after cytoreduction of primary advanced epithelial ovarian
cancer. MATERIALS AND METHODS: Thirty consecutive women with Stage 3 or 4
invasive primary epithelial ovarian cancer were treated with cytoreductive
surgery. Postoperatively patients received 100 mg/m(2) of cisplatin, 200 mg/m(2)
of paclitaxel, and 500 mg/m(2) of cyclophosphamide IV q 21 days x 3 cycles with
300 microg of G-CSF daily x5 beginning the first day following chemotherapy. This
was followed by carboplatin AUC-5 and 135 mg/m(2) of paclitaxel IV q 21 days x3.
All administration was outpatient and paclitaxel was administered over 3 h.
RESULTS: Eighty percent of tumors were Stage 3C, 77% were serous, and 60% were
Grade 3. Maximum cytoreduction to <2 cm was performed in 96%. Median follow-up is
30 months. Sixty-three percent of patients developed recurrence. Currently 50% of
patients are alive with no evidence of disease. Estimated mean survival is 61
months and estimated mean progression-free survival is 29 months. No patient
developed thrombocytopenia, neutropenic sepsis, significant neuropathy, or renal
toxicity. CONCLUSION: This treatment regimen resulted in minimal toxicity and,
following aggressive cytoreduction, produced good progression-free and overall
survival.
PMID- 11006040
TI - Absence of PTEN repeat tract mutation in endometrial cancers with microsatellite
instability.
AB - OBJECTIVE: PTEN, a tumor suppressor gene shown to be frequently mutated in
endometrial cancers, has been suggested to be a target of microsatellite
instability (MSI)-driven mutagenesis. We set out to investigate the relationship
between MSI and PTEN mutation in a large series of primary endometrial
carcinomas. METHODS: Thirty-nine MSI-positive endometrial cancers were evaluated
by single-strand conformational variant analysis and direct sequencing to screen
all nine PTEN exons for mutation. RESULTS: Fifteen specimens (38%) demonstrated
16 PTEN mutations. We observed only one alteration in the poly-adenine repeat of
exon 8 that is suggested to be a target for mutation in endometrial cancers with
MSI. Seven of 16 (44%) mutations in our series were deletions of >/=3 bp, a class
of mutation not usually associated with tumors with defective DNA mismatch
repair. To determine the significance of this high frequency of deletion, 26
additional endometrial cancers without MSI were matched with the 39 MSI-positive
cancers for the prognostic factors of tumor histology, stage, grade, and patient
race. The MSI-positive tumors had a significantly higher frequency of deletions
involving >/=3 bp when compared with the MSI-negative group (5/11 versus 0/10, P
= 0.035). CONCLUSIONS: Repeat tract mutation in PTEN is an uncommon event in MSI
positive cancers. Deletion of >/=3 bp in this gene is more common in MSI-positive
cancers when compared with tumors without MSI.
PMID- 11006041
TI - Cervical cancer outcomes analysis: impact of age, race, and comorbid illness on
hospitalizations for invasive carcinoma of the cervix.
AB - OBJECTIVE: The aim of this study was to evaluate the association of age, race,
and comorbid illness with procedures and complications in hospitalized patients
with invasive carcinoma of the cervix in a statewide population-based database
over a 3-year period. METHODS: Hospitalizations were classified into homogeneous
subgroups based on a diagnosis of invasive cervical cancer. Cancer-related
complications and comorbid diseases were evaluated. chi(2) and t tests determined
differences in means or proportions. Linear regression techniques were applied to
build models for hospitalization charges and lengths of stay (LOS). RESULTS:
There were 1009 admissions. The mean age was 49.5, with a median age of 46 (21
100, SD 15.4). Of the total, 606/1009 (60%) were white, 354/1009 (35%) were
African-American (AA), and 5% were "other" races. AAs were more likely to have
Medicaid or be uninsured (44% vs 23%, P = 0. 001) and were more likely to be
admitted for an emergency (unadjusted odds ratio (OR) = 1.6; 1.2-2.2), to have a
comorbid illness (P = 0.001), to be admitted for a cancer-related complication (P
= 0.036), to be admitted for a transfusion (P = 0. 01), and to be admitted for
radiation therapy rather than surgery (P = 0.001). The following were associated
with LOS and higher hospital costs: emergency admissions for complications of
cancer, comorbid illness, and older age. CONCLUSIONS: Racial differences exist in
patterns of admission, type of therapy, and severity of illness; however, there
were no differences in charges or LOS for similar procedures. The large
percentage of African-Americans uninsured or insured by government-supported
programs indicates the potential impact of public policy on the care of these
patients. Socioeconomic status rather than phenotypic appearance may be a more
important determinant of outcome.
PMID- 11006042
TI - Phase 2 evaluation of topotecan administered on a 3-day schedule in the treatment
of platinum- and paclitaxel-refractory ovarian cancer.
AB - PURPOSE; The aim of this study was to investigate the toxicity and efficacy of a
more convenient topotecan administration schedule (in contrast to the "standard"
1.5 mg/m(2)/day x 5 days q 21 days) in the management of platinum- and paclitaxel
refractory ovarian cancer. METHODS: Patients with clinically defined platinum-
and paclitaxel-refractory ovarian cancer participating in this phase 2 trial
conducted by the Gynecologic Cancer Program of the Cleveland Clinic Taussig
Cancer Center received topotecan at a dose of 1.5 mg/m(2)/day x 3 days on a 21
day schedule. Both dose escalations and reductions were permitted in the protocol
design. RESULTS: A total of 29 patients (median age: 61; range: 43-80) were
treated with this modified topotecan schedule. These individuals had received a
median of two prior regimens (range: 1-4) (retreatment with a platinum agent or
paclitaxel considered a single regimen). The median number of topotecan courses
delivered was 3 (range: 1-7). Major toxicity included grade 4 neutropenia (24% of
patients); neutropenic fever (10%); grade 3 thrombocytopenia (10%); and
requirement for blood transfusion (14%). Dose escalation was possible, and dose
reductions required, in 14 and 28% of patients, respectively. Two patients
exhibited evidence of a clinically relevant response to treatment. CONCLUSION:
This 3-day topotecan program is more convenient and less toxic than the standard
5-day regimen. The limited level of activity observed is not inconsistent with
that previously reported for the 5-day topotecan infusion schedule in
platinum/paclitaxel-refractory ovarian cancer. Further investigation will be
required to document the clinical utility of a 3-day topotecan schedule in a less
heavily pretreated and more chemosensitive patient population.
PMID- 11006043
TI - Low-grade endometrial stromal sarcoma of the ectocervix after therapy for breast
cancer.
AB - OBJECTIVE: Low-grade endometrial stromal sarcoma is an uncommon, indolent uterine
sarcoma that can arise in extrauterine locations. The objective of this study was
to report on a previously unpublished site of origin for a low-grade endometrial
stromal sarcoma. METHODS: A case of a low-grade endometrial stromal sarcoma
arising in the ectocervix after goserelin hormonal therapy for breast cancer was
studied. RESULTS: Low-grade endometrial stromal sarcoma can arise in the
ectocervix even in the absence of endometriosis. CONCLUSION: Low-grade
endometrial stromal sarcoma should be included in the differential diagnosis of
sarcomas of the ectocervix.
PMID- 11006044
TI - Desmoplastic small round cell tumor with primary ovarian involvement: case report
and review.
AB - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive,
malignant neoplasm that has recently been characterized. It has not been
associated with a primary visceral organ. In women, cases are even more rare and
often have some ovarian involvement. CASE: An 11-year-old girl presented with
abdominal pain, nausea, and vomiting. A CT scan revealed a large heterogeneous
pelvic mass with cystic components and an 8-cm midabdominal mass. During
exploratory laparotomy, the patient was found to have a pelvic mass measuring 12.
9 cm replacing normal ovarian tissue. The midabdominal mass was also removed.
Pathology, cytology, and immunohistochemistry confirmed a desmoplastic small
round cell tumor. Even with aggressive surgical and medical intervention, the
patient died 11 months after initial diagnosis. CONCLUSION: We present a rare
small cell tumor that is associated with ovarian involvement. The prognosis in
these patients is extremely poor and very few survivals have been reported.
PMID- 11006045
TI - Endometrial carcinoma remaining after term pregnancy following conservative
treatment with medroxyprogesterone acetate.
AB - BACKGROUND: Successful pregnancies after conservative progestin treatment to
young women with endometrial carcinoma have recently been reported. However, it
is not known for certain whether the lesion is completely eradicated in such
patients. We present a case of residual endometrial carcinoma after term
pregnancy which had been treated conservatively before the pregnancy began. CASE:
A 28-year-old woman with endometrial carcinoma received conservative treatment
with high-dose medroxyprogesterone acetate (MPA) and then conceived. After
delivery at term, atypical cells were found in the endometrial curettage
specimen. A hysterectomy was performed 6 months after delivery and revealed the
presence of a small focus of intramucosal, grade 1, endometrioid-type
adenocarcinoma. Immunohistochemically, the tumor cells were positive for estrogen
and progesterone receptors. CONCLUSION: We concluded that while MPA treatment had
been effective, it had not completely eradicated the carcinomatous lesion, which
remained during and after the term pregnancy.
PMID- 11006046
TI - Cortical bone distribution in the femoral neck of strepsirhine primates.
AB - The thickness of the inferior and superior cortices of the femoral neck was
measured on X-rays of 181 strepsirhine primate femora representing 24 species.
Neck length, neck depth and neck-shaft angle were also measured. The strength of
the femoral neck in frontal bending was estimated by modeling the neck as a
hollow cylinder, with neck depth as the outer diameter and cortical thickness
representing the superior and inferior shell dimensions. Results indicate that
the inferior cortex is always thicker than the superior cortex. The ratio of
superior to inferior cortical thickness is highly variable but distinguishes two
of the three locomotor groups in the sample. Vertical clingers and leapers have
higher ratios (i.e., a more even distribution of cortical bone) than quadrupeds.
The slow climbers tend to have the lowest ratios, although they do not differ
significantly from the leapers and quadrupeds. These results do not confirm prior
theoretical expectations and reported data for anthropoid primates that link
greater asymmetry of the cortical shell to more stereotypical hip excursions. The
ratio of superior to inferior cortical thickness is unrelated to body mass,
femoral neck length, and neck-shaft angle, calling into question whether the
short neck of strepsirhine primates acts as a cantilever beam in bending. On the
other hand, the estimated section moduli are highly correlated with body mass and
neck length, a correlation that is driven primarily by body mass. In conclusion,
we believe that an alternative interpretation to the cantilever beam model is
needed to explain the asymmetry in bone distribution in the femoral neck, at
least in strepsirhine primates (e.g., a thicker inferior cortex is required to
reinforce the strongly curved inferior surface). As in prior studies of cross
sectional geometry of long bones, we found slightly positive allometry of
cortical dimensions with body mass.
PMID- 11006047
TI - Mass change, environmental variability and female fertility in wild Propithecus
verreauxi.
AB - Accurate estimates of mass and size are important in a wide range of research
questions in population and evolutionary biology, and yet such data are still
rare for wild primates. This study presents detailed longitudinal data from a
large population of wild indriids, and demonstrates links between fluctuations in
body mass, environmental cycles, and reproduction. Understanding these links is a
necessary step toward explaining the function and evolution of distinctive
features of lemur biology and behavior. During the first 12 years of an ongoing
study of the sifaka, Propithecus verreauxi verreauxi, at Beza Mahafaly in
southwest Madagascar, 320 animals were captured and weighed throughout the year.
Adult males and females exhibit seasonal cycles of mass loss, with females losing
significantly more mass than males. In 2 drought years this pattern was
especially pronounced. Compared to lighter females, females who were heavier at
the time of the mating season were more likely to give birth in the following
birth season. By showing (1) seasonally greater mass loss in reproductive females
compared to males, particularly in drought years, (2) a close link between female
mass and fertility, and (3) an uncoupling of the periods of highest body mass and
of gestation and lactation, these results suggest that energy acquisition and
storage are critically important in the life history strategies of female sifaka,
and that "capital breeding" may be a feature of sifaka reproductive strategies.
PMID- 11006048
TI - The Iberomaurusian enigma: north African progenitor or dead end?
AB - Data obtained during an ongoing dental investigation of African populations
address two long-standing, hotly debated questions. First, was there genetic
continuity between Late Pleistocene Iberomaurusians and later northwest Africans
(e.g., Capsians, Berbers, Guanche)? Second, were skeletally-robust
Iberomaurusians and northeast African Nubians variants of the same population?
Iberomaurusians from Taforalt in Morocco and Afalou-Bou-Rhummel in Algeria,
Nubians from Jebel Sahaba in Sudan, post-Pleistocene Capsians from Algeria and
Tunisia, and a series of other samples were statistically compared using 29
discrete dental traits to help estimate diachronic local and regional affinities.
Results revealed: (1) a relationship between the Iberomaurusians, particularly
those from Taforalt, and later Maghreb and other North African samples, and (2) a
divergence among contemporaneous Iberomaurusians and Nubian samples. Thus, some
measure of long-term population continuity in the Maghreb and surrounding region
is supported, whereas greater North African population heterogenity during the
Late Pleistocene is implied.
PMID- 11006049
TI - Paleosols, stable carbon isotopes, and paleoenvironmental interpretation of
Kanapoi, Northern Kenya.
AB - This study uses the interpretation of paleosol features at Kanapoi, Kenya (4.2
3.4 Ma) to reconstruct the ecosystem occupied by Australopithecus anamensis. The
paleosols at Kanapoi provide a unique and fortuitous opportunity, in that the
bulk of the hominid specimens derive from paleosols, providing direct evidence of
the environment that the Kanapoi hominids occupied. Seven named types of
paleosols are recognized at Kanapoi, each representing a trace fossil of the
local ecosystem during soil formation. The hominid-bearing Dite paleosols provide
evidence that A. anamensis inhabited areas of semi-arid, seasonal climate regimes
with mean annual precipitation ranging from about 350-600 mm. The in situ hominid
collections from Dite paleosols show that A. anamensis at least occasionally
occupied relatively open low tree-shrub savanna vegetation formed in well drained
settings, and may have preferred these conditions over other poorly drained
soils. The relatively open conditions of Dite paleosols existed within a
spatially variable ecosystem, characterized by a mosaic of environments, ranging
from forb-dominated edaphic grassland to gallery woodland, providing a larger
view of the mixed ecosystem in which A. anamensis lived. Synthesis of
paleoenvironmental indicators of A. anamensis at Kanapoi and Allia Bay, Kenya
suggests that as early as 4 Ma hominids thrived in varied ecosystems.
PMID- 11006050
TI - A corrected reconstruction and interpretation of the Homo erectus calvaria from
Ceprano, Italy.
PMID- 11006051
TI - A re-appraisal of Ceprano calvaria affinities with Homo erectus, after the new
reconstruction.
PMID- 11006053
TI - Pesticides. A message from Preventive Medicine and your physician.
PMID- 11006052
TI - Tobacco use among Massachusetts youth: is tobacco control working?
AB - BACKGROUND: This paper examines whether the Massachusetts Tobacco Control Program
is affecting the rates of smoking and smokeless tobacco use among Massachusetts'
youth. METHODS: School survey data from the Massachusetts Prevalence Study were
analyzed to estimate differences between 1993 and 1996 rates of youth cigarette
and smokeless tobacco use, attitudes toward smoking, and awareness of cigarette
ads and promotions of antismoking messages. RESULTS: Lifetime and Current Smoking
rates declined significantly among middle school males, contrasting with stable
national trends. Among girls in this age group, Lifetime and Current Smoking did
not change significantly. Hispanic middle school students exhibited a significant
decline in Lifetime Use. There were no significant changes in Lifetime or Current
Smoking rates among high school students. Lifetime use of smokeless tobacco
declined among middle school students while Current Use declined among both
middle and high school students. Students reported declines in awareness of
cigarette ads or promotions and increases in awareness of antismoking messages.
CONCLUSIONS: These results provide evidence for cautious optimism regarding the
impact of tobacco control, but indicate that these efforts should begin earlier
and that additional research is needed to understand and address the problems of
tobacco use by girls.
PMID- 11006054
TI - Smokers with multiple behavioral risk factors: how are they different?
AB - OBJECTIVE: The first aim of the present investigation was to examine cross
sectional differences between smokers who engage in additional health risk
behaviors (i.e., high-fat diets and low physical activity levels) and those who
do not that could affect readiness for smoking cessation treatment and treatment
prognosis. The second aim was to examine prospective associations between risk
factor status and smoking outcomes (i.e., cessation and quit attempts). DESIGN:
Data were derived from baseline and 1-year follow-up surveys for the SUCCESS
project, a randomized trial of worksite smoking interventions conducted in 24
worksites in Minneapolis/St. Paul, Minnesota. Included in the analyses were 2,149
study participants who reported smoking at baseline. METHODS: Current smokers
were categorized into one of three "risk groups": the "1 additional risk factor"
group (i.e., either low physical activity level or high dietary fat intake), the
"2 additional risk factor" group (i.e., both low physical activity and high
dietary fat intake), and the "smoker only" group (i.e., neither low physical
activity nor high dietary fat intake). Mixed model regression analyses examined
cross-sectional associations between risk group status and baseline demographic
variables, smoking dependency, social environments for smoking, and health
problems. Prospective associations between baseline risk group status and 1-year
follow-up cessation attempts and quits were also examined. RESULTS: At baseline,
risk factor status was associated with smoking dependency for both men and women.
Women smokers with at least one additional risk factor reported a greater number
of cigarettes smoked per day, higher Fagerstrom Nicotine Dependence scores, and
lower self-efficacy for refraining from smoking in a variety of situations
compared with smokers with no additional risk factors. Men smokers with at least
one additional risk factor reported higher Fagerstrom Nicotine Dependence scores
compared with smokers with no additional risk factors. Women smokers with at
least one additional risk factor were more likely to report being encouraged to
quit by co-workers compared with smokers with no other risk factors. No
relationship between risk factor status and social pressure to quit was observed
among men. Prospective analyses indicated that baseline risk factor status was
marginally related to smoking outcome at 1-year follow-up; however, these
relationships were attenuated considerably when controlling for smoking
dependence. Relationships between risk factor status and smoking outcomes were
stronger for men. CONCLUSION: Results indicated that the presence of multiple
health risk behaviors was related to more serious problems with smoking. However,
the presence of additional risk factors did not strongly affect prognosis for
smoking cessation.
PMID- 11006055
TI - Hypocholesterolemic effect of soymilk supplementation with usual diet in
premenopausal normolipidemic Japanese women.
AB - BACKGROUND: The hypocholesterolemic effect of soy protein concentrates on
normolipidemic subjects still remains unclear. Our objective is to assess the
effect of soymilk supplementation, a whole soy product, with usual diet on serum
lipids in normolipidemic subjects. METHODS: We conducted a randomized controlled
trial on 60 premenopausal normolipidemic Japanese women. After excluding 8
subjects whose initial serum concentration of total cholesterol or
triacylglycerol was higher than 220 mg/dL (5.69 mmol/L) or 160 mg/dL (1.81
mmol/L), respectively, we encouraged the subjects in the soymilk-supplemented
group (n = 27) to consume 400 mL (408 g) of commercial regular soymilk daily
during two menstrual cycles. There were no significant differences in variables,
including nutrient intake, between the soymilk-supplemented and control (n = 25)
groups before the intervention. RESULTS: After the trial, we observed a
significant decrease of 10.9 mg/dL, or 5.3%, in serum concentration of total
cholesterol in the soymilk-supplemented group. During the intervention, nutrient
intake assessment showed significant increases in nutrient densities of vitamin
E, polyunsaturated fatty acids, isoflavones, and P/S ratio and decreases in total
energy and nutrient densities of vitamin C and green tea in this group. A
statistically significant decrease in serum total cholesterol could still be
observed even after excluding the estimated hypocholesterolemic effects of
soymilk's polyunsaturated fatty acids. CONCLUSIONS: Our results suggest the
hypocholesterolemic effect of soymilk, a traditional whole soy product, in Asian
countries in normolipidemic subjects.
PMID- 11006056
TI - Patient reminder letters to promote annual mammograms: a randomized controlled
trial.
AB - BACKGROUND: This study assessed the effects of a reminder letter from a physician
(relative to a mammography facility letter or no letter) on appointment
compliance among women 50-74 years of age due for an annual screening mammogram.
METHODS: A total of 1,562 women were randomly as signed to the groups. Each Group
1 subject received a reminder letter from her physician, each Group 2 subject
received a reminder letter from her mammography facility, and Group 3 served as a
control group. RESULTS: The return rates for Groups 1, 2, and 3 were 47.7, 46.6,
and 28.3%, respectively; the overall difference was significant using a chi(2)
analysis (P < 0.001). Bonferroni pairwise comparisons indicated no difference
between Groups 1 and 2 but significant differences (P < 0.001) between Group 3
and the other two groups. Logistic regression indicated that relative to Group 3,
the adjusted odds of returning for Groups 1 and 2 were 2.37 and 2.24,
respectively. CONCLUSIONS: Mammography providers and their patients likely will
benefit from in-reach reminder systems. Physicians who do not use reminder
systems should refer their patients to facilities that use these systems.
PMID- 11006057
TI - Psychosocial influences on older adults' interest in participating in bowel
cancer screening.
AB - BACKGROUND: As part of a multicenter, randomized controlled trial of the efficacy
of flexible sigmoidoscopy for the prevention of bowel cancer, an investigation of
the predictors of screening interest was carried out in a subsample of older
adults. METHOD: The aim of the study was to establish the predictive power of the
Health Belief Model (HBM) and to evaluate the contribution of HBM elements in
mediating the effect of other demographic and health variables which have been
found to be associated with screening interest and participation. A total of
5,099 participants were sent a postal questionnaire which examined screening
interest, attitudes toward screen ing (benefits and barriers), perceived bowel
cancer risk, bowel cancer worry, bowel symptoms, health status, state anxiety,
and optimism. A total of 3,648 questionnaires were returned completed, giving a
response rate of 71.5%. RESULTS: The results showed that threat, barriers, and
benefits explained 47% of the variance in interest. Demographic and health
variables were also associated with screening interest, although most of their
effect was mediated by the HBM constructs. DISCUSSION: This community study in
older adults showed a high level of interest in participating in screening. The
large sample size provided the opportunity to test the value of the HBM model and
to examine mediation of demographic and health variables. The HBM proved to be a
good model of screening interest. These results further our understanding of the
decision processes in participating in cancer screening and point to directions
to increase the level of participation in community samples.
PMID- 11006058
TI - Population frequency distributions of HDL, HDL(2), and HDL(3) cholesterol and
apolipoproteins A-I and B in healthy men and women and associations with age,
gender, hormonal status, and sex hormone use: the Stanford Five City Project.
AB - BACKGROUND: The purpose of this study is to present population-based frequency
distribution data for several lipoprotein-related variables and to examine their
associations with gender, age, menopausal status, and sex hormone use. METHODS:
High-density lipoprotein cholesterol (HDL-C), HDL(2)-C, HDL(3)-C, apolipoprotein
(Apo) A-I, and Apo B were measured in a population-based sample of 1, 027 healthy
adults from four California cities who participated in the 1989-1990 survey of
the Stanford Five City Project. These data were examined cross-sectionally with
sociodemographic and other related variables. RESULTS: Relative to men, all of
the HDL-related parameters-HDL-C, HDL(2)-C, HDL(3)-C, Apo A-I-were significantly
higher and Apo B levels were significantly lower among women (P < 0. 001).
Menopausal status was not associated with HDL-related parameters, but Apo B
levels were higher in post- versus premenopausal women (P < 0.001). Among women,
HDL-C and Apo A-I levels were higher in oral contraceptive and estrogen
replacement therapy users (P = 0.003). Most of the significant findings remained
statistically significant after adjusting for age, body mass index, smoking,
energy expenditure, and alcohol intake. CONCLUSIONS: These population-based data
indicate that gender, menopausal status, and the use of sex hormones among women
are associated with differential levels of one or more of HDL-C, HDL(2)-C, HDL(3)
C, Apo A-I, and Apo B, independent of age and a broad set of lifestyle factors.
PMID- 11006059
TI - Associations of HDL, HDL(2), and HDL(3) cholesterol and apolipoproteins A-I and B
with lifestyle factors in healthy women and men: the Stanford Five City Project.
AB - BACKGROUND: Measures of the two major high-density lipoprotein (HDL)
subfractions, HDL(2) and HDL(3), and the major apolipoproteins of HDL and low
density lipoprotein (LDL), Apo A-I and Apo B, may be etiologically important
factors in the development of coronary artery disease. The association of
lifestyle factors with these lipoprotein-related variables remains unclear.
METHODS: HDL-C, HDL(2)-C, HDL(3)-C, Apo A-I, and Apo B levels were determined in
a population-based sample of 1,027 healthy women and men aged 25-64 years, from
four California cities who participated in the 1989/1990 survey of the Stanford
Five City Project. In this cross-sectional study we examined the independent
associations of these lipoprotein-related variables with body mass index (BMI),
cigarette smoking, daily energy expenditure, alcohol intake, dietary intake, and
hormone use (oral contraceptives and estrogen replacement therapy). RESULTS: In
general, BMI and alcohol intake were the strongest independent predictors of the
lipoprotein-related variables. The negative association of BMI with HDL-C was
attributable primarily to the association with the HDL(2)-C subfraction, while
for alcohol intake the positive association with HDL-C was attributable primarily
to the association with HDL(3)-C, particularly in men. Among men, but not women,
energy expenditure was a significant independent predictor of each of the
lipoprotein-related variables, with positive associations observed for HDL-C,
HDL(2)-C, HDL(2)-C, and Apo A-I and a negative association observed for Apo B (P
< 0.005). CONCLUSIONS: Data from this population-based sample suggest that
specific lifestyle factors are more strongly associated with some lipoprotein
related variables than with others, with notable gender differences.
PMID- 11006060
TI - Telephone counseling as adjuvant treatment for nicotine replacement therapy in a
"real-world" setting.
AB - BACKGROUND: Physicians prescribing nicotine replacement therapy (NRT), or health
plans covering NRT, often want their patients to receive adjuvant behavioral
treatment. However, how to do that in a "real world" is unclear. This paper
reports results from a public health program that uses proactive telephone
counseling as support for physician advice and provides adjuvant treatment for
NRT users. METHODS: Participants were NRT users (N = 8,832) who called the
California Smokers' Helpline, a statewide cessation service that provides
proactive counseling, one session before NRT use and multisessions after the
smokers received NRT. After receiving NRT, some participants discontinued the
counseling while others continued with follow-up sessions. A subset of the 8,832
participants (n = 664) was interviewed 13 months later for quitting status.
RESULTS: After receiving NRT, 79% of the participants continued with counseling
and received 4.2 sessions on average, while 21% of them received only one
session. Overall, 82.8% of all participants made a quit attempt. Nicotine patch
users were more likely to make an attempt than nicotine gum users (85.2% vs
66.3%), but the relapse probability was the same for these attempts. Those who
received multiple counseling were more likely to make an attempt than those
receiving single counseling (84.4% vs 77.1%) and were more likely to stay quit
for 1 year (25.6% vs 16.1%). CONCLUSIONS: Proactive telephone counseling is a
promising adjuvant treatment for NRT users in a "real-world" setting: a
convenient referral service for supporting health plans or physicians who advise
their patients to quit smoking.
PMID- 11006061
TI - Smokers ages 50+: who gets physician advice to quit?
AB - BACKGROUND: Smoking-related morbidity and mortality, and benefits associated with
quitting, extend across the life span. Health care provider interventions enhance
quitting. The present study examined perceived influence of physician advice to
quit and characteristics of subjects receiving this advice. METHODS: Subjects
were 1,454 smokers ages 50+ with at least one physician visit in the past year.
Subjects were surveyed at baseline for receipt of and reactions to physician
advice to quit and for smoking, health, and demographic characteristics. RESULTS:
Over half of subjects welcomed physician advice to quit, about half said the
advice influenced their quitting decision "extremely" or "quite a lot," and about
one-third indicated that it increased their confidence in quitting. Physicians
were more likely to advise sicker patients, indicated by poorer health status, at
least one past year hospitalization, and presence of cardiovascular,
cerebrovascular, or respiratory diseases. CONCLUSIONS: Midlife and older smokers
reacted generally favorably to physician advice to quit. Physicians were more
likely to advise patients with commonly recognized smoking-related diseases.
Discrepancies were noted in advice given to sicker vs healthier patients.
Additional physician training in less commonly recognized smoking-related
illnesses, intervening with healthier patients to prevent disease, and enhancing
patients' confidence in quitting may improve outcomes.
PMID- 11006062
TI - Cardiovascular disease risk factor intervention in low-income women: the North
Carolina WISEWOMAN project.
AB - OBJECTIVES: The North Carolina WISEWOMAN project was initiated to evaluate the
feasibility of expanding an existing cancer screening program to include a
cardiovascular disease (CVD) screening and intervention program among low-income
women. METHODS: Seventeen North Carolina county health departments were
designated as minimum intervention (MI), and 14 as enhanced intervention (EI).
The EI included three specially constructed counseling sessions spanning 6 months
using a structured assessment and intervention program tailored to lower income
women. RESULTS: Of the 2,148 women screened, 40% had elevated total cholesterol
(> or = 240 mg/dL), 39% had low high-density lipoprotein cholesterol (HDL-C)
levels (< 45 mg/dL), and 63% were hypertensive (systolic blood pressure 140
and/or diastolic blood pressure > or = 90 mm Hg or on hypertensive medication).
The majority of women (86%) had at least one of these three risk factors. Seventy
six percent were either overweight or obese. After 6 months of follow-up in the
EI health departments, changes in total cholesterol levels, HDL-C levels,
diastolic blood pressure, and BMI were observed (-5.8 mg/dL, -0.9 mg/dL, -1.7 mm
Hg, and -0.3 kg/m(2), respectively), but were not significantly different from MI
health departments. A dietary score that summarized fat and cholesterol intake
improved by 2.1 units in the EI group, compared with essentially no change in the
MI group. CONCLUSIONS: Expanding existing cancer screening programs to include
CVD intervention was feasible and may be an effective means for promoting
healthful dietary practices among low-income women.
PMID- 11006063
TI - A randomized trial of a tailored, self-help dietary intervention: the Puget Sound
Eating Patterns study.
AB - BACKGROUND: This study evaluated a tailored, multiple-component self-help
intervention designed to promote lower fat and higher fruit and vegetable
consumption. METHODS: Participants were 1,459 adults selected at random,
stratified by sex and age (18-34, 35-54, 55-69), from enrollees of a large health
maintenance organization. After completing a baseline telephone survey,
participants were randomized to receive the intervention (consisting of a
computer-generated personalized letter, a motivational phone call, a self-help
manual, a package of supplementary materials, computer-generated behavioral
feedback based on a self-administered food frequency questionnaire, and
newsletters) or to receive no materials. Evaluation was based on 1,205 (86.5%)
participants who completed both a 3- and a 12-month follow up survey. RESULTS:
The intervention effect +/- SE for fat, based on a diet habits questionnaire, was
-0.10 +/- 0.02 (P < 0.001), corresponding to a reduction of approximately 0.8
percentage points of percentage energy from fat. For fruits and vegetables, the
intervention effect was 0.47 +/- 0.10 servings/day (P < 0.001). Intervention
effects were similar across age and sex groups. CONCLUSIONS: Tailored, self-help
interventions can effectively promote dietary change among both men and women and
among younger as well as older adults.
PMID- 11006064
TI - Hypercholesterolemia and 5-year risk of development of coronary heart disease
among university and school workers in Jeddah, Saudi Arabia.
AB - BACKGROUND: A study was performed among university and school employees as a step
in detecting the prevalence of coronary heart disease (CHD) risk factors among
school and university staff and the relation of the various risk factors to
hypercholesterolemia and to predict the 5-years probability of development of
CHD. METHODS: All university staff and a sample of school workers in Jeddah were
included in the study. Data were collected by interview and self-administered
questionnaires, as well as by direct observation and measurement of weight,
height, blood pressure, and total blood cholesterol. Logistic regression analysis
was performed to identify the impact of various risk factors on
hypercholesterolemia. The 5-year risk of development of CHD was calculated to
identify the proportion at highest risk. RESULTS: Some CHD risk factors were
detected among the participants as 18.8% were current cigarette smokers, around
half were classified as overweight, and 19.9% were classified as hypertensive.
Hypercholesterolemia was present in 10.1% and was significantly related to older
age (40 years and over) and place of work. The estimated risk of CHD in the
coming half-decade for those classified in the fifth quintile was 0.068. The
Q(5)/Q(1) ratio has shown that those classified in the fifth quintile were at 3.6
times more risk of developing CHD in the coming 5 years than those classified in
the first quintile. CONCLUSION: CHD risk factors are becoming prevalent in our
society. The risk of development of CHD in the coming decades is not trivial.
Short- and long-term health strategies are recommended to decrease the risk of
CHD and improve the quality of life.
PMID- 11006065
TI - Evaluation of a population-based screening for type 2 diabetes: a community-based
screening project in Puli, Taiwan.
AB - BACKGROUND: A Markov method incorporating the relationships between prevalence,
incidence, and mortality with respect to type 2 diabetes was used to assess a
population-based screening for this disease. METHODS: Data from a population
based screening project for residents of Puli, Taiwan, over 30 years of age (n=
1,219) were used to estimate the annual incidence of asymptomatic type 2
diabetes, the prevalence to incidence (P/I) ratio, and the hazard rate of death
due to type 2 diabetes. These parameters were employed to develop a Markov
process to evaluate the effects of early detection of type 2 diabetes on the risk
of death from this disease in a simulated population (n= 10,000) receiving
biennial, 5-year interval, or no screening. RESULTS: The estimated annual
incidence, average duration from asymptomatic to symptomatic type 2 diabetes (P/I
ratio), and hazard rate for death from this disease were 0.86% (95% CI 0.50
1.48), 10 years (95% CI 7.69-14.01), and 1.1% per year, respectively. This yields
an optimal screening interval of 5 years. Simulation of a 5-year interval
screening regimen versus no screen ing yielded a relative risk reduction of 31%
(95% CI 12-46%). A similar value was found for a biennial screening regime.
CONCLUSIONS: The results suggest that early detection of type 2 diabetes via a
community-based screening project in developing countries with high prevalence is
worthwhile.
PMID- 11006066
TI - 7-year stability of blood pressure in the Canadian population.
AB - BACKGROUND: The purpose of the study was to examine the 7-year stability of
systolic (SBP) and diastolic (DBP) blood pressures in the Canadian population.
METHODS: The sample included 1,503 participants 7-69 years of age from the 1981
Canada Fitness Survey who were remeasured in Campbell's Survey of 1988. Both SBP
and DBP were adjusted for the effects of body mass index (BMI) using regression
procedures. RESULTS: Interage correlations from baseline to follow-up ranged from
-0.17 to 0.61 for SBP and from -0.22 to 0. 51 for DBP. With few exceptions,
correlations were positive and significant, and were highest and most consistent
in adulthood. Further, between 27 and 39% of participants in the upper or lower
quintiles in 1981 remained there in 1988. There were few differences in adiposity
between those who remained in the upper or lower quintiles and those who did not.
One exception was that males who remained in the upper quintile of SBP had
greater values for BMI, sum of skinfolds, and waist circumference at baseline.
Among adults, the best predictor of future blood pressure was baseline blood
pressure, which accounted for between 12 and 34% of the variance in follow-up
blood pressure, followed by age, follow-up BMI, and, in females, baseline
physical activity levels. CONCLUSIONS: Blood pressure demonstrated low to
moderate stability over 7 years in Canada, and baseline level of adiposity was
related to the stability of SBP in males.
PMID- 11006067
TI - Predictors of stage of adoption for colorectal cancer screening.
AB - BACKGROUND: Although colorectal cancer is the third most common cancer in women,
little is known about predictors of adherence to screening. METHODS: A randomly
selected sample of 202 predominantly low-income and African-American women were
interviewed. Knowledge of, attitudes and beliefs about, and practices related to
flexible sigmoidoscopy (FS) screening were assessed. RESULTS: The majority of
participants were in the precontemplation stage of adoption (56%). There were
significant differences by stage of adoption for FS beliefs, FS barriers, risk of
developing colorectal cancer, worry about getting colorectal cancer, and
physician recommendation to get a FS. Predictors of adherence to FS guidelines
were perceiving fewer barriers to getting a FS and having a physician recommend a
FS. CONCLUSION: Seventy-two percent of the women in this study were nonadherent
to FS screening guidelines. Psychosocial factors play an important role in
screening for colorectal cancer. Ways of reducing barriers and increasing
physician recommendations should be explored.
PMID- 11006068
TI - Attitudes, beliefs, and knowledge as predictors of nonattendance in a Swedish
population-based mammography screening program.
AB - BACKGROUND: The effectiveness of mammography screening could be improved if
factors that influence nonattendance were better understood. METHODS: We examined
attitudes, beliefs, and knowledge in relation to nonattendance in a population
based mammography screening program, using a case-control design. Data were
collected from November 1997 to March 1998 through telephone interviews with 434
nonattenders and 515 attenders identified in a population-based mammography
register in central Sweden. The questions asked drew primarily upon the
components constituting the Health Belief Model. RESULTS: Multivariate analysis
showed that nonattendance was most common among women within the highest quartile
of perceived emotional barriers, compared to women within the lowest quartile (OR
= 4.81; 95% CI 2.96-7.82). Women who worried most about breast cancer were more
likely to attend than those who worried least (OR = 0.09; 95% CI 0.02-0.31).
Women with the highest scores of perceived benefits were more likely to attend
than women with the lowest ones (OR = 0.35; 95% CI 0.08-0.75). Other factors
associated with nonattendance were less knowledge about mammography and breast
cancer, lack of advice from a health professional to participate, and very poor
trust in health care. CONCLUSIONS: Our findings suggest that increased
participation in outreach mammography screening programs can be achieved through
enhancement of breast cancer awareness and possibly by reducing some of the
modifiable barriers. mammography; mass screening; breast cancer; attitudes;
Sweden.
PMID- 11006069
TI - Effectiveness of interventions to improve follow-up after abnormal cervical
cancer screening.
AB - OBJECTIVE: The purpose of this study was to determine the effectiveness of
interventions designed to improve follow-up after an abnormal Pap smear. METHODS:
We performed a qualitative meta-analysis of interventions designed to improve
follow-up after an abnormal Pap smear and included studies that met the following
criteria: randomized or concurrently controlled study design, defined outcomes,
and data available for abstraction. Interventions were classified as behavioral,
cognitive, sociologic, or combined strategies (e.g., behavioral and cognitive).
Abnormal Pap smears were defined as any test result requiring additional follow
up. Effectiveness was measured by the rate of compliance with recommended follow
up. RESULTS: Twenty-two interventions in 10 studies met the inclusion criteria.
Cognitive interventions utilizing interactive telephone counseling were the most
effective, improving compliance by 24 to 31%. Behavioral interventions, such as
patient reminders, were also effective, increasing follow-up by up to 18%. Not
all of these results achieved statistical significance. The single sociologic
intervention we identified used video-taped peer discussions to provide a message
about abnormal Pap smears and appropriate follow-up. This intervention was not
associated with increased follow-up after an abnormal test. The effectiveness of
interventions using multiple types of strategies to improve follow-up was
inconsistent. CONCLUSIONS: Cognitive strategies led to the greatest improvement
in compliance with follow-up of abnormal Pap smear screening tests. Extension of
similar interventions to follow-up of abnormal breast and colon cancer screening,
development of physician- and system-targeted interventions, and evaluation of
the cost-effectiveness of these strategies are important priorities for future
research.
PMID- 11006070
TI - Feasibility of a tailored intervention to improve preventive care use in women.
AB - BACKGROUND: Women age 50 years and older are in need of multiple preventive
health care services. Despite recent improvements in rates of delivery of
preventive care services, especially within managed care organizations,
substantial numbers of women are still being underscreened. Efforts to improve
delivery of preventive care services have often focused on one outstanding
service despite the fact that patients often are in need of many services.
METHODS: A total of 893 women age 50 to 55 years were mailed a self-administered
survey to identify outstanding preventive health care service needs. Patients in
need of three or more outstanding preventive health care services were identified
from survey respondents to participate in a feasibility study evaluating a
tailored, customized intervention called Tic Tac Health. RESULTS: Five-hundred
ninety-one women returned the survey (67%). Four-hundred forty-eight (76%) women
were in need of one or more preventive health services; 92 (16%) were in need of
three or more. Twenty-two patients (24%) completed the Tic Tac Health card. The
women who completed the card were similar to those who did not. CONCLUSIONS:
Despite documented physician visits, presence of managed care health insurance,
and a designated primary care provider, a significant number of women are still
in need of multiple preventive health services. An intervention targeting
multiple preventive health services was demonstrated to be both feasible and
effective. Further evaluation via a randomized controlled trial should be
conducted to determine if an intervention like Tic Tac Health would be an
effective modality for improving rates of receipt of multiple preventive health
care services.
PMID- 11006071
TI - Cancer of the colon and rectum in California: trends in incidence by
race/ethnicity, stage, and subsite.
AB - BACKGROUND: Incidence and mortality from cancer of the colon and rectum have
declined in recent years in the United States and California, but reasons for the
decline are unknown. METHODS: Age-adjusted site-specific and stage-specific
incidence rates were calculated for approximately 9,000 cases of in situ cancer
and 120,000 cases of invasive cancer of the colon and rectum diagnosed between
1988 and 1996 among California residents and reported to the California Cancer
Registry. Trends in incidence over time were measured using the estimated annual
percent change. RESULTS: Among non-Hispanic whites there was a decline in all
sites and stages, but the decrease was most pronounced for rates of in situ and
regional/distant tumors in the rectum and sigmoid which declined by about 4 to 7%
a year. For tumors in the proximal colon, the decrease was statistically
significant only for regional/distant tumors which declined about 2% a year.
Among blacks, there was an approximately 7% annual decline in the incidence of
regional/distant tumors of the rectum in women and a nearly 3% a year decrease in
regional/distant tumors of the proximal colon in men. The decline in rates for
Hispanics and Asian/Pacific Islanders was smaller and less consistent than for
non-Hispanic whites. CONCLUSIONS: The results confirm a overall decline in all
stages of cancer of the colon and rectum in California, particularly among non
Hispanic white men and women. The decrease was most pronounced for tumors in the
rectum and sigmoid colon and may be attributable to screening.
PMID- 11006072
TI - The role of regucalcin in nuclear regulation of regenerating liver.
AB - Regucalcin was discovered in 1978 as a Ca(2+)-binding protein that does not
contain EF-hand motif of Ca(2+)-binding domain [Yamaguchi, M., and Yamamoto T.,
Chem. Pharm. Bull. 26, 1915-1918, 1978]. The name regucalcin was proposed for
this Ca(2+)-binding protein, which can regulate liver cell functions related to
Ca(2+). Regucalcin has been demonstrated to play a multifunctional role in liver
and kidney cells, for which regucalcin mRNA expression and its protein content
are pronounced. Hepatic regucalcin mRNA expression has been shown to be mediated
through signaling pathway of Ca(2+)/calmodulin-dependent protein kinase, protein
kinase C, and tyrosine kinase. AP-1- and NF-1-like factors can bind to the
promotor region of the rat regucalcin gene to mediate the Ca(2+) response for
transcriptional activation. Growing evidence supports the view, moreover, that
regucalcin plays an important role in the regulation of Ca(2+) signaling from the
cytoplasm to nuclei in the proliferative cells of regenerating rat liver. Also,
regucalcin has been demonstrated to be transported to liver nucleus, and it can
inhibit nuclear protein kinase, protein phosphatase, and DNA and RNA synthesis in
regenerating liver. Regucalcin plays a physiologic role in the control for
overexpression of proliferative cells. Regucalcin has been proposed to be an
important regulatory protein in nuclear signaling system.
PMID- 11006073
TI - Synthesis of stereoisomeric analogues of endomorphin-2, H-Tyr-Pro-Phe-Phe-NH(2),
and examination of their opioid receptor binding activities and solution
conformation.
AB - All sixteen stereoisomeric analogues of endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH(2))
were synthesized by Fmoc-strategy using solid phase methods. Although synthetic
endomorphin-2 exhibited similar mu- and delta-opioid receptor-binding activity to
the natural compound, endomorphin-2 analogues containing d-amino acid isomers
exhibited lower interaction with mu-receptors depending on the particular
combination. The data clearly indicated that the three dimensional structure of
endomorphin-2 with the natural l-configuration was the most suitable for binding
within the mu receptor, but specific residues are important for activity.
Circular dichroism studies verified that changes in chirality of amino acids in
the endomorphin-2 sequence resulted in structural conformation. These alterations
significantly reduced the specificity for mu-receptor-binding sites.
PMID- 11006074
TI - A novel gene (retinovin) expressed selectively in the early stage of chick
retinal development.
AB - To understand molecular mechanisms of retinal development, genes expressed
selectively only in the early stage of retinal development were isolated by
subtractive hybridization based on suppression polymerase chain reaction. The
retina has no layered structure in 7-day chick embryos, in contrast with the
fully developed multilayered structure of neurons in 15-day embryos. The
subtraction between cDNA derived from retinal tissues at these different stages,
followed by repeat rounds of 5'-RACE (rapid amplification of cDNA ends) and 3'
RACE, led to isolation of a novel gene with an open reading frame encoding a
putative protein with 753 amino acids. Its specific expression in the 7-day
embryonic retina was confirmed by Northern blot analysis. The gene, named
"retinovin," would be used as a marker for identifying retinal stem cells present
at the early stage of retinal development.
PMID- 11006075
TI - AMP-Activated protein kinase is activated by the stimulations of G(q)-coupled
receptors.
AB - The AMP-activated protein kinase (AMPK) functions as a metabolic sensor that
monitors cellular AMP and ATP levels. Platelet-activating factor (PAF) activates
endogeneous AMPKalpha1 in Chinese hamster ovary cells expressing the PAF receptor
coupled with both G(i) and G(q), but its activity was not inhibited after
treatment with islet-activating protein. Norepinephrine and bradykinin also
activated AMPKalpha1 in cells expressing the G(q)-coupled alpha(1b)-adrenergic
receptor and bradykinin receptor, respectively. Stimulations of the G(i)-coupled
alpha(2A)-adrenergic receptor, fMet-Leu-Phe receptor, prostaglandin EP3alpha
receptor, and G(s)-coupled beta(2)-adrenergic receptor did not activate
AMPKalpha1. AMPKalpha1 thus is activated specifically by stimulation of G(q)
coupled receptors. G(q)-coupled receptors transmit the signal for GLUT4
translocation and glucose uptake through an insulin-independent pathway. However,
direct activation of AMPKalpha1 with treatment of 5-aminoimidazole-4-carboxamide
1-beta-d-ribofuranoside did not trigger GLUT4 translocation nor stimulate glucose
uptake in our cells. Thus, activation of AMPKalpha1 via G(q) is not sufficient to
trigger GLUT4 translocation or stimulate glucose uptake.
PMID- 11006076
TI - Complete amino acid sequence of Japanese chestnut agglutinin.
AB - The complete amino acid sequence of Japanese chestnut (Castanea crenata Sieb. et
Zucc.) agglutinin (CCA) was determined. Analysis by SIMS of the acidic peptide
obtained by pepsin digestion revealed that the N-terminal amino acid sequence
should be Acetyl-Met-Glu-Glu. Prior to sequence analysis, redetermination of
cysteine residues indicated the presence of one cysteine residue per subunit. The
complete sequence was determined by endoproteinase Arg-C and Achromobacter
protease I digestion, and CNBr cleavage. CCA consists of 309 amino acid residues
with a high content of glycine (16.5 mol%) and one cysteine residue. The
calculated molecular mass was 33, 387 Da including the N-terminal acetyl group. C
terminal sequence analysis of intact CCA gave only one sequence, HMEYF,
indicating that no heterogeneous CCA formed by posttranslational cleavage at the
C-terminal region, as occurs in some legume lectins. Analysis of the sequence of
CCA itself revealed that CCA could be divided into two structural domains, the N
domain and the C-domain, almost at the center. These domains share about 35%
identical residues, so CCA has a repeat sequence. Also, both domains show a
homology to jacalin-related lectins with 27-38% identity. These results suggest
that the structure of CCA resembles two molecules of jacalin-related lectin.
PMID- 11006077
TI - Edema induction by the disintegrin-like/cysteine-rich domains from a Bothrops
atrox hemorrhagin.
AB - Viperine and crotaline snake venoms contain one or more hemorrhagic
metalloproteases called hemorrhagins. The most potent hemorrhagins belong to the
P-III class and have, in addition to the protease domain, disintegrin-like and
cysteine-rich domains. Although proteolytic degradation of vascular endothelium
basement membrane has been established to be the main factor responsible for
hemorrhage, several studies reveal other factors that actually do facilitate this
process. Recent evidence has shown that the nonprotease domains of the P-III
class hemorrhagins are able to inhibit the platelet aggregation by blocking
essential procoagulant integrins on platelets. In this study we report the
identification of a hemorrhagin from Bothrops atrox venom. This enzyme, a P-III
class metalloprotease, undergoes an apparent spontaneous degradation, releasing a
proteic fragment containing the disintegrin-like/cysteine-rich domains. This
fragment shows the capability to induce an edematogenic process, suggesting the
existence of a still unknown nonenzymatic mechanism of vascular permeability
increase.
PMID- 11006078
TI - ATP synthesis and heat production during Ca(2+) efflux by sarcoplasmic reticulum
Ca(2+)-ATPase.
AB - Vesicles derived from the sarcoplasmic reticulum of rabbit white skeletal muscle
were loaded with Ca(2+) and used to measure the rates of Ca(2+) efflux, heat
production, and ATP synthesis from ADP and P(i). It was found that the Ca(2+)
ATPase can function in three different forms: (i) it absorbs heat from the medium
(5 Kcal/mol Ca(2+)) when the efflux was coupled with ATP synthesis; (ii) it
converts the energy derived from the gradient into heat (30 Kcal/mol Ca(2+)) when
Mg(2+) is removed from the medium and the synthesis of ATP is impaired; and (iii)
the ATPase becomes uncoupled when the different ligands of the enzyme are removed
from the medium. As a result, there is no ATP synthesis and no heat production or
absorption during Ca(2+) efflux. The Ca(2+) efflux, ATP synthesis, and heat
production were inhibited by thapsigargin, a specific inhibitor of the Ca(2+)
ATPase.
PMID- 11006079
TI - Suppression of CFTR-mediated Cl(-) secretion by enhanced expression of epithelial
Na(+) channels in mouse endometrial epithelium.
AB - The present study investigated the effect of enhanced expression of epithelial
Na(+) channels (ENaC) on the cystic fibrosis transmembrane conductance regulator
(CFTR)-mediated Cl(-) secretion in the mouse endometrium using the short-circuit
current technique. The amiloride sensitivity of the basal current of the cultured
endometrial epithelia was found to vary with the magnitude of the basal current,
the higher the basal current the greater its sensitivity to amiloride, indicating
possible elevation of ENaC expression. However, the magnitude of the forskolin
induced Isc, previously demonstrated to be mediated by CFTR, decreased as the
amiloride sensitivity of the basal current increased, suggesting a possible
inhibitory effect of elevated expression of ENaC on CFTR-mediated Cl(-)
secretion. The Matrigel concentration for culturing the endometrial epithelia was
found to affect the amiloride sensitivity of the basal current as well as the
forskolin-induced Isc in opposite directions. However, competitive RT-PCR
demonstrated that the expression of both ENaC and CFTR was enhanced in Matrigel
treated culture, suggesting that the reduced forskolin-induced Isc with enhanced
amiloride sensitivity was not due to a reduction in CFTR expression, but rather
suppression of CFTR function by enhanced ENaC expression. In addition to the
previously demonstrated inhibition of ENaC by activation of CFTR, the present
results reveal possible regulation of CFTR by ENaC. The interaction between the
two may be one of the underlying mechanisms for balancing Na(+) absorption and
Cl(-) secretion across epithelia.
PMID- 11006080
TI - Molecular cloning of testis-abundant finger Protein/Ring finger protein 23
(RNF23), a novel RING-B box-coiled coil-B30.2 protein on the class I region of
the human MHC.
AB - We have identified a genomic DNA fragment, using the PCR method with degenerate
oligonucleotide primers which contain the conserved sequence of the RING finger
domain. Using the DNA fragment as a probe, a novel cDNA was cloned from human and
mouse testis. The cDNA had a domain structure of the typical RING-B box-coiled
coil (RBCC)-B30.2 domain and therefore was named testis-abundant finger protein
(tfp). Indeed, the transcript was highly expressed in the testis, although it was
also found ubiquitously in various organs by Northern blot analysis. The tfp gene
was mapped at the class I region of the human MHC (major histocompatibility
complex), within which some known RBCC-B30.2 proteins such as RFP, RFB30/HERF1,
AFP, and HZF had been localized. These findings demonstrate that several RBCC
B30.2 proteins including tfp, which are non-HLA proteins, are clustered within
the class I region of the human MHC.
PMID- 11006081
TI - Multiple transcripts of the human Cu,Zn superoxide dismutase gene.
AB - We have identified five alternatively spliced transcripts of the gene for human
Cu,Zn superoxide dismutase (SOD1), a causative gene for autosomal dominant
amyotrophic lateral sclerosis (ALS). The splice variants of wild-type or mutant
SOD1 were expressed in a tissue-specific manner; therefore, their expression may
be regulated to modify SOD1 function. In addition, the expression in the brain
implies that variants may play a role in the nervous system, the region involved
in ALS. Immunoblot study of HeLa cells transfected with two variants encoding C
terminal truncated proteins did not show the proteins of expected size. However,
this observation is consistent with the previous study of C-terminal truncated
mutant proteins that cause ALS, suggesting that both variant and mutant proteins
may share certain properties, such as instability or insolubility in the cytosol.
These findings suggest that the splice variants may contribute to a physiological
function of SOD1 or to a pathological mechanism in ALS.
PMID- 11006082
TI - Inorganic Polyphosphate/ATP-NAD kinase of Micrococcus flavus and Mycobacterium
tuberculosis H37Rv.
AB - An enzyme with both inorganic polyphosphate [poly(P)]- and ATP-dependent NAD
kinase activities was isolated from Micrococcus flavus. The enzyme was a dimer
consisting of 34 kDa subunits, and was named poly(P)/ATP-NAD kinase. Internal
amino acid sequences of the enzyme showed homologies with some function-unknown
proteins released on the GenBank database. Among such proteins, hypothetical
Rv1695 protein (Accession No. Z98268-16), which was encoded by a gene named
"Rv1695" on genomic DNA of Mycobacterium tuberculosis H37Rv, was proposed to be
poly(P)-dependent NAD kinase. By cloning and expression in Escherichia coli,
Rv1695 was shown to encode poly(P)/ATP-NAD kinase and named ppnk. The ppnk
product, recombinant-poly(P)/ATP-NAD kinase (Ppnk) was purified and
characterized. The enzyme was a tetramaer consisting of 35 kDa subunits when
expressed in E. coli. Poly(P)/ATP-NAD kinases of M. flavus and Ppnk of M.
tuberculosis H37Rv specifically and completely phosphorylated NAD by utilizing
commercially available poly(P)s and nucleoside triphosphates as phosphoryl
donors.
PMID- 11006083
TI - ppGpp-dependent leuO expression in bacteria under stress.
AB - Despite the known potential transcription regulatory role of leuO gene product,
LeuO, the condition when leuO expresses during bacterial growth cycle remains
unclear. Mechanistically, leuO expression was shown to be part of promoter relay
mechanism, however, the factor(s) responsible for the regulation of leuO
expression is not known. Combining Northern and Western results, we demonstrate
in the present communication that leuO expression is normally low and enhanced
when bacteria are in transition from exponential growth to stationary phase. The
stationary phase-associated leuO expression is ppGpp dependent and rpoS (sigma(s)
factor) independent.
PMID- 11006084
TI - Enzymes leading to the nucleotide sugar precursors for exopolysaccharide
synthesis in Burkholderia cepacia.
AB - Based on the chemical composition of the exopolysaccharide produced by the cystic
fibrosis bacterial isolate Burkholderia cepacia IST408, we postulated and
confirmed, based on the specificity of enzymes detected in crude cell-free
extracts, the pathway leading to the presumptive activated sugar precursors: UDP
D-glucose, UDP-D-galactose, UDP-D-glucuronic acid, GDP-D-mannose, and GDP-D
rhamnose. Results also suggest that regulation of the expression of the mucoid
phenotype in B. cepacia does not occur at the level of synthesis of any of these
enzymes.
PMID- 11006085
TI - Induction of NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase expression by
androgens in human prostate cancer cells.
AB - Prostate cancer cells are known to express cyclooxygenases (COXs) and synthesize
prostaglandins. Catabolism of prostaglandins in these cells remains to be
determined. Induction of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase
(15-PGDH), a key metabolic inactivation enzyme, was investigated in androgen
sensitive LNCaP cells and in hormone-independent PC3 cells. 15-PGDH was found to
be induced by dihydrotestosterone or testosterone in a time- and dose-dependent
manner in LNCaP but not in PC3 cells as shown by activity assay and immunoblot
analysis. However, prostaglandin synthetic enzymes, COX-1 and COX-2, were not
found to be induced by androgens. Induction was also achieved by 17beta-estradiol
and progesterone, although to a lesser extent. Induction of 15-PGDH was not
blocked by steroid receptor antagonist, RU 486, nor by antiandrogen, flutamide.
However, induction was inhibited by tyrosine kinase inhibitor, genistein, and by
ERK kinase inhibitor, PD 98059, but not by protein kinase C inhibitor, GF109203X.
These results suggest that androgens induce 15-PGDH gene expression through an
unconventional nongenomic pathway.
PMID- 11006086
TI - Effects of carvedilol on isolated heart mitochondria: evidence for a
protonophoretic mechanism.
AB - Carvedilol (?1-[carbazolyl-(4)-oxy]-3-[2-methoxyphenoxyethyl)amino]-pro panol-(2)
?) is a novel compound used in clinical practice for the treatment of congestive
heart failure, mild to moderate hypertension, and myocardial infarction.
Carvedilol was also shown to protect cardiac mitochondria from oxidative stress
events. Because mitochondria are the main suppliers of ATP for cardiac muscle
work, a study of the effects of carvedilol in mitochondrial bioenergetics is
necessary to fully understand the basis of its protective role in myocardial
energetics. In this work we show that carvedilol acts as an uncoupler of
oxidative phosphorylation, decreasing mitochondrial electric potential (DeltaPsi)
by a weak protonophoretic mechanism. Theoretical studies were carried out to
determine the relevance of conformation and proton affinity of the protonable
amino side-chain group in the proton-shuttling activity across the inner
mitochondrial membrane. BM910228, a hydroxylated metabolite of carvedilol, was
also studied for comparison with the parent compound. Implications for the
protective role of carvedilol in heart mitochondrial bioenergetics are discussed.
PMID- 11006088
TI - Expression of the Na(+)/Ca(2+) exchanger ameliorates ionomycin-induced cell
death.
AB - PC12 cells were stably transfected with cDNA encoding the Na(+)/Ca(2+) exchanger
(NCX1.4). A robust Na(+)-dependent Ca(2+) uptake confirmed the functional
expression of the protein. When NCX1. 4 expressing cells (NO) and vector
transfected control cells (VC) were exposed to 0.5-20 microM ionomycin for 6 h, a
dose-dependent increase in LDH release was observed. LDH release was
significantly reduced in NO when compared with VC. When either VC and NO were
treated with 3 microM ionomycin and 1.1 mM EGTA, the increase in LDH release was
nearly abolished. However, when VC and NO were treated with ionomycin and then
EGTA was added 2 min later, LDH release remained elevated. These data suggest
ionomycin-induced cell death was Ca(2+) dependent and expressing NCX1.4 may have
ameliorated cell death by reducing elevated [Ca(2+)](I).
PMID- 11006087
TI - Pyrrolidine dithiocarbamate inhibits TNF-alpha-dependent activation of NF-kappaB
by increasing intracellular copper level in human aortic smooth muscle cells.
AB - Pyrrolidine dithiocarbamate (PDTC) is a metal-chelating compound that acts as
antioxidant or pro-oxidant and is widely used to study redox regulation of cell
function. In the present study, we investigated effects of PDTC and another
antioxidant, N-acetyl-l-cysteine (NAC), on TNF-alpha-dependent activation of NF
kappaB in human aortic smooth muscle cells (HASMC). Treatment of the cells with
TNF-alpha induced the activation of p65/p50 heterodimer NF-kappaB and increased
the mRNA levels of monocyte chemoattractant protein (MCP)-1. Pretreatment with
PDTC markedly suppressed the NF-kappaB activation and expression of MCP-1 by
inhibiting IkappaB-alpha degradation. In contrast, NAC had no effect. PDTC
concomitantly increased the intracellular levels of copper, and
bathocuproinedisulfonic acid, a non-cell-permeable chelator of Cu(1+), inhibited
the PDTC-induced increase in intracellular copper level and reversed the PDTC
effects on IkappaB-alpha, NF-kappaB, and MCP-1. These results indicate that TNF
alpha-dependent expression of MCP-1 in HASMC is tightly regulated by NF-kappaB
and that intracellular copper level is crucial for the TNF-alpha-dependent
activation of NF-kappaB in HASMC.
PMID- 11006090
TI - Three-hybrid strategy reveals a peptide segment that specifically binds to the 3'
untranslated region of NF-IL6 mRNA.
AB - The 3'UTR of eukaryotic mRNA is an important regulation region, on which many
trans factors act. In recent years, a series of 3'UTRs were shown to have tumor
suppressor function, including the 3'UTR of the human nuclear factor for
interleukin-6 (NF-IL6 3'UTR). To understand molecular basis for this function, we
have tried to isolate genes encoding protein factors acting on the RNA of NF-IL6
3'UTR. Here we show that, by using a yeast three-hybrid system, a cDNA fragment
was successfully isolated. This cDNA was allowed to express in E. coli, and its
expression product, a polypeptide of ca. 70 amino acids long, was shown to
specifically bind to the NF-IL6 3'UTR RNA. A search in GenBank did not reveal
homologous sequences. Therefore, this cDNA fragment may be a part of the gene of
a novel NF-IL6 3'UTR specific binding protein.
PMID- 11006089
TI - Calcium-modulating cyclophilin ligand desensitizes hormone-evoked calcium
release.
AB - The Ca(2+)-modulating cyclophilin ligand (CAML) protein causes stimulation of
transcription factors via activation of a store-operated Ca(2+) entry pathway.
Since CAML is widely expressed in mammalian tissues, it may be an important
regulator of Ca(2+) store function. In the present study, we investigated the
consequence of CAML overexpression on Ca(2+) signaling using rapid confocal
imaging of Fluo3-loaded NIH3T3 fibroblasts. Control and CAML-expressing cells
gave concentration-dependent responses to the Ca(2+) mobilizing agonist ATP. CAML
expression reduced the sensitivity of the cells so that higher concentrations of
ATP were needed to achieve global Ca(2+) waves. The amplitudes of Ca(2+) waves
were significantly reduced in CAML expressing cells, consistent with earlier
suggestions that CAML causes depletion of internal Ca(2+) stores. With low ATP
concentrations, only local Ca(2+) release events were observed. CAML did not
affect the characteristics of these local Ca(2+) signals, suggesting that it does
not directly affect Ca(2+) release channels.
PMID- 11006091
TI - Alternative splicing forms of the human CD1D gene in mononuclear cells.
AB - CD1d is a critical molecule for the presentation of lipid antigens to natural
killer (NK) T cells. To investigate the molecular complexity of CD1d,
alternatively spliced transcripts in peripheral blood mononuclear cells from
three healthy subjects were analyzed by PCR and sequencing methods. We found
eight alternatively spliced variants of the CD1D gene (V1-V8), seven of which are
newly established variants (V2-V8). V1 and V4 are in-frame; however, the other
six variants (V2, V3, V5-V8) are out-of-frame. V1, V2, V4, and V5 lack a beta(2)
microglobulin binding site (alpha3 domain), indicating the unstable presentation
of the CD1d molecule on the surface. In V2 and V5, the transmembrane region is
absent, supporting a soluble CD1d. In the V3-V8 variants, the antigen binding
region (alpha1 and alpha2 domains) is partially defective, suggesting incomplete
functional products. In contrast, the V1 and V2 transcripts bear the complete
antigen binding site, resulting in functional proteins. Especially, the V2
splicing variant might function as an inhibitory soluble CD1d molecule and
regulate the presentation of antigens on APC to NKT cells.
PMID- 11006092
TI - Characterization of NAADP(+) binding in sea urchin eggs.
AB - Nicotinic acid adenine dinucleotide phosphate (NAADP(+)) is a pyridine nucleotide
which has been shown to release Ca(2+) from intracellular membranes in
echinoderms, Ascidiae, mammals, and plants. NAADP releases Ca(2+) via a mechanism
independent of ryanodine and inositol 1,4,5-trisphosphate (IP(3)) receptors and
the NAADP(+) receptor is likely to be located on a separate organelle. We have
investigated the binding characteristics of NAADP(+) to its receptor in sea
urchin egg homogenates. NAADP(+) binds to a saturable membrane-bound site with
high affinity (K(d) = 193 +/- 35. 7 pM). NAADP(+) associates to its receptor with
a t(1/2) of approximately 7 min while dissociation does not occur during the time
course of the experiment. Furthermore, NAD(+), NAAD(+), ADP, or ATP cannot
displace NAADP(+) binding. The structurally related molecules NADP(+) and NADPH
displayed a markedly lower affinity for the binding site with K(d)'s 500- and
25,000-fold higher than NAADP(+), respectively. This discrepancy between oxidized
and reduced forms of NADP(+) might suggest that NAADP(+) signaling is itself
regulated by the redox state of the cell.
PMID- 11006093
TI - Molecular cloning and genomic organization of the mouse AE2 anion exchanger gene.
AB - The molecular organization of the AE2 (SLC4A2) gene, a member of the multigene
family encoding sodium-independent chloride/bicarbonate anion exchangers, has
previously been described in both humans and rats. In these two species, AE2
shows alternate promoter usages and tissue-specific expression of isoforms in a
similar, but not identical, fashion. Here we report the molecular cloning and
organization of the entire mouse AE2 gene. The gene consists of 23 exons and 22
introns and spans about 17 kb. Moreover, it drives transcription of N-terminal
truncated isoforms from alternate promoter sequences in a way analogous to that
described for rat and/or human orthologs. Thus, sequences within intron 2
function as overlapping alternate promoters for truncated isoforms AE2b(1) and
AE2b(2), and sequences of intron 5 drive transcription of isoforms AE2c(1) and
AE2c(2). Each of these variants has a specific alternative first exon, while
remaining exons are common to the complete form of the message AE2a, the
diversity at 5' leading to different N-termini in corresponding encoded proteins.
As expected, mouse AE2 promoter sequences and the patterns of tissue expression
of AE2 isoforms resemble rat counterparts more closely than human ones.
PMID- 11006094
TI - Genomic organization of the human kallikrein gene family on chromosome 19q13.3
q13.4.
AB - Kallikreins are a subgroup of serine proteases with diverse physiological
functions. Recently, growing evidence indicates that many kallikrein genes are
involved in malignancy. In rodents, kallikreins are encoded by a large multigene
family, but in humans only three kallikreins were thought to exist. Based on the
homology between the human and rodent kallikrein loci, we studied a 300 kb region
of genomic sequences around the putative KLK1 gene locus on chromosome 19q13.3
q13.4. By using linear sequence information, restriction analysis, end
sequencing, PCR and blotting techniques, as well as bioinformatic approaches, we
were able to construct the first detailed map of the human kallikrein gene
family. Comparative analysis of genes located in this area, provides strong
evidence that the human kallikrein gene family locus on chromosome 19 is
considerably larger than previously thought, containing at least fifteen genes.
We have established, for the first time, the common structural features that
apply to all members of the expanded kallikrein multigene family. Our map
specifies the distance between genes to one base pair accuracy, the relative
location, and the direction of transcription of all 15 genes. Determination of
the true size of the kallikrein family in humans is important for our
understanding of the contribution of the kallikreins to human biology and
pathophysiology.
PMID- 11006095
TI - Hypoxia/hypoglycemia-induced amino acid release is decreased in vitro by
preconditioning.
AB - The aim of this study was to investigate the effects of preconditioning on amino
acid neurotransmitter release, induced by hypoxia/hypoglycaemia, from rat brain
cortical slices. Tissue, perfused with artificial cerebrospinal fluid (aCSF) at
37 degrees C with zero glucose and gassed with 95% nitrogen and 5% carbon
dioxide, showed a fivefold increase in glutamate release with little effect on
gamma-aminobutyric acid (GABA) release. Preconditioning, with three 5-min periods
of hypoxia/hypoglycaemia preceding continuous hypoxia/hypoglycaemia,
significantly decreased glutamate release whilst significantly elevating GABA
release. These results suggest that GABA may reduce the release of glutamate and
consequently decrease the neurotoxic effects of glutamate.
PMID- 11006096
TI - Identification of five new isoforms of murine thrombopoietin mRNA.
AB - Thrombopoietin (Tpo) is the major physiologic regulator of platelet production.
Its gene is expressed in many organs and appears constitutive in liver and
kidney. However, inducible gene expression in the bone marrow and spleen have
been reported as well as the presence of a number of isoforms, presumably arising
from alternative splicing. We have identified five new murine Tpo isoforms,
designated Tpo 5 to Tpo 9. Alternative splicing of these isoforms, in addition to
the already-reported four isoforms, occurs around exon 7, the last exon, with
insertion of some intron sequences or deletion of exon sequences. Studies of
tissue distribution indicate that Tpo 4 is the major isoform in lymph nodes and
bone marrow. The roles of these isoforms in hematopoietic regulation are unknown,
but the presence of inducible Tpo mRNA in the marrow microenvironment may
contribute to platelet or stem cell homeostasis.
PMID- 11006097
TI - Inhibiting proteasomes in human HepG2 and LNCaP cells increases endogenous
androgen receptor levels.
AB - Treating HepG2 cells with MG132 for 4 h to inhibit proteasomal activity increased
androgen receptor immunoreactivity in two major bands with molecular weights of
102 and 110 kDa by 77% each (P < 0. 05). MG132 treatment also increased the
overall level of polyubiquitinated proteins between 66 and 220 kDa by 140% (P <
0.05). Antiubiquitin immunoreactivity comigrating with the androgen receptor
bands was also increased by MG132 treatment. Two other proteasome inhibitors,
lactacystin and epoxomycin, caused similar increases in the androgen receptor in
HepG2 cells. Proteosome-inhibition studies conducted in LNCaP cells also showed
that the two major androgen receptor bands with molecular weights of 102 and 110
kDa were increased by 85 and 115%, respectively (P < 0. 05 for both) by MG132
treatment. Overall levels of polyubiquitinated proteins with molecular weights
between 66 and 220 kDa increased 365%. Ubiquitin immunoreactivity comigrating
with the androgen receptor bands was also significantly increased. Thus
inhibiting proteasomes in two human androgen-responsive cell lines increases
endogenous androgen receptor levels as well as androgen receptor-associated
ubiquitin-modified immunoreactivity. The regulation of steady-state levels of
endogenous androgen receptor by proteasomal degradation could be involved in its
rapid turnover in the absence of ligand and would provide a mechanism for
limiting androgen responses. A PEST sequence similar to one in the vitamin D
receptor is present in the hinge region of all known mammalian androgen
receptors, suggesting that it may function in proteasome-mediated androgen
receptor turnover.
PMID- 11006099
TI - Probing the topology of the glutamate receptor GluR1 subunit using epitope-Tag
insertions.
AB - At least two different models for the transmembrane topology of the glutamate
receptor subunits have been proposed. We investigated some features of these two
models for the GluR1 subunit by inserting epitope tags between residues Lys(502)
Pro(503), Ala(632)-Glu(633), Lys(712)-Pro(713), or after the C-terminal residue
Leu(889). The accessibility of the tags then was detected using a tag-specific
antibody before and after detergent-permeabilizing oocytes expressing the tagged
subunits. The epitope tag inserted between residues Lys(712)-Pro(713) is
extracellular and after Leu(889) intracellular. Epitope tags inserted between
residues Lys(502)-Pro(503) and residues Ala(632)-Glu(633) were not detectable.
Collectively, these results provide supporting evidence for a previously proposed
topological model of GluR subunits containing an N-terminal extracellular domain,
three transmembrane domains, the first two of which are bridged by a reentrant
membrane pore-lining loop, and an intracellular C-terminal domain.
PMID- 11006098
TI - Genistein induces apoptosis of RPE-J cells by opening mitochondrial PTP.
AB - Although previous studies demonstrated that genistein-induced apoptosis of
various cell types including RPE-J cells, the involvement of mitochondrial events
in such types of apoptosis has not been demonstrated to date. In this
investigation of genistein-induced apoptosis of RPE-J cells, genistein induced
the reduction of the mitochondrial membrane potential and the release of
cytochrome c to cytosol. A mitochondrial permeability transition pore (PTP)
blocker bongkrekic acid prevented the reduction of the mitochondrial membrane
potential and cytochrome c release, and consequently abolished caspase-3
activation, nuclear condensation, and DNA fragmentation. On the other hand, zVAD
fmk did not inhibit the mitochondrial event such as the reduction of the
mitochondrial membrane potential and cytochrome c release although it prevented
caspase-3 activation, nuclear condensation, and DNA fragmentation. Taken
together, genistein induces apoptosis of RPE-J cells by opening the mitochondrial
PTP, and the mitochondrial event in this type of apoptosis is caused
independently of caspase.
PMID- 11006100
TI - Regulation of proteins involved in insulin signaling pathways in differentiating
human adipocytes.
AB - In the present study we have examined the proteins involved in the insulin
signaling cascade during and after differentiation of human adipocyte precursor
cells and their correlation with glucose uptake. The differentiation of human
adipocytes was characterized by a two- to threefold stimulation of glucose
transport in response to insulin and a marked increase protein expression for the
insulin receptor, IRS-1, GLUT-4, PI 3-kinase, and PKB, with respect to
undifferentiated cells. In contrast, there were small changes in the protein
expression of IRS-2, and no changes in PKC zeta and MAP kinases, although basal
MAP kinase activity and GLUT-1 protein were reduced during differentiation. In
conclusion, there are quantitative differences in the regulation of IRS-1 and
other proteins during differentiation which may contribute to more efficient
insulin signaling leading to glucose uptake in mature fat cells. Alterations in
this pattern may reflect or contribute to an insulin-resistant state.
PMID- 11006101
TI - Wavelength-programmed solute release from photosensitive liposomes.
AB - Liposomes of dipalmitoylphosphatidylcholine containing a photochromic lipid "Bis
Azo PC" release entrapped solutes on exposure to UV light. We have now
demonstrated that on addition of cholesterol (up to 25 mol%) to the liposomal
membrane the liposomes also release their contents in response to visible light
in the region of 470 nm, to which liposomes lacking steroid are insensitive. In a
mixed population of liposomes prepared with and without cholesterol, this enables
wavelength-dependent release of entrapped solutes on sequential exposure to
visible and UV light. Furthermore, the cholesterol-containing liposomes allow
stepped partial release of entrapped solute following multiple periods of short
visible illumination. It is suggested that the cholesterol-containing liposomes
may be potentially useful for drug delivery and for "caging" of reagents.
PMID- 11006102
TI - Hepatic copper accumulation induces DNA strand breaks in the liver cells of Long
Evans Cinnamon strain rats.
AB - Effects of accumulation of copper and iron on the production of DNA strand breaks
were investigated in Long-Evans Cinnamon (LEC) strain rats that spontaneously
develop fulminant hepatitis. Copper and iron accumulated in the liver of LEC rats
in an age-dependent manner from 4 to 15 weeks. Low-copper food prevented the
accumulation of copper in the liver, but did not prevent accumulation of iron.
When the amounts of DNA single strand breaks were estimated by comet assay, the
number of DNA strand breaks in the liver cells of rats fed standard food
increased with age from 4 to 15 weeks. The number of DNA strand breaks in the
liver cells from rats fed low-copper food were the same as those of rats at 4
weeks of age. Thus, the copper accumulation in the liver of LEC rats induced DNA
strand breaks, but accumulation of iron did not.
PMID- 11006103
TI - The subcellular location of nucleoside analog phosphorylation is a determinant of
synergistic effects of hydroxyurea.
AB - The ribonucleotide reductase inhibitor hydroxyurea exhibits synergistic
pharmacological activity with several nucleoside analogs used in antiviral and
anticancer chemotherapy. We have used a cell model system where a deoxycytidine
kinase (dCK)-deficient cell line was reconstituted with genetically engineered
dCK targeted to the cytosol, the nucleus, or the mitochondria to investigate how
the subcellular location of nucleoside analog phosphorylation affected the
synergistic effects of a ribonucleotide reductase inhibitor. Hydroxyurea showed
synergistic cytotoxicity with the nucleoside analogs 1-beta-d
arabinofuranosylcytosine and 2-chloro-2'-deoxyadenosine when dCK was expressed in
the cytosol or in the nucleus, but not when dCK was expressed in the
mitochondria. These data indicate that the synergistic effect of ribonucleotide
reductase inhibition is limited to nucleoside analogs phosphorylated in the
cytosol or the cell nucleus.
PMID- 11006104
TI - Myristoylation alters retinoic acid-induced down-regulation of MARCKS in
immortalized hippocampal cells.
AB - The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent PKC
substrate in the brain, which has been implicated in brain development,
cytoskeletal remodeling, calcium/calmodulin signaling, and neuroplasticity. The
sequence of the Macs gene codes for a protein that has three highly conserved
domains including a 5' myristoylation region and a 25-amino-acid phosphorylation
site domain (PSD), which are involved in anchoring MARCKS to the cellular
membrane. In this study, we examined the role of the myristoylation signal in the
regulation of MARCKS in transfected rat hippocampal cells (H19-7) following
retinoic acid (RA) treatment. A mutant MARCKS lacking the myristoylation signal
was engineered by substitution of alanine for glycine at position 2 of the Macs
gene and was found to be exclusively expressed in the cytosol fraction of
transfected cells. Exposure of the wild-type MARCKS-transfected cells to RA
resulted in an apparent shift of MARCKS from the membrane to the cytosol, while
the total protein of wild-type MARCKS was not significantly changed. In contrast,
RA-exposed cells transfected with the mutant MARCKS revealed a dramatic reduction
of expression of MARCKS protein in both cytosol and total protein fractions.
These data suggest that the absence of the myristoyl moiety may not only alter
the anchoring of the protein to the membrane but also play a novel role in
modulating cellular levels of MARCKS protein in response to RA.
PMID- 11006106
TI - Characterization of l-asparaginase fused with a protective ScFv and the
protection mechanism.
AB - A fusion protein of the protective scFv linked to the C-terminus of ASNase via
(Gly(4)Ser)(6) peptide was constructed. The ASNase-scFv fusion protein expressed
in Escherichia coli exists mainly in the form of inclusion bodies, and a small
amount of it was soluble. The soluble form was purified by four-step purification
and it has been demonstrated that ASNase-scFv fusion exists as a dimer. By assay
of the stability against proteolysis, the ASNase-scFv fusion was found to be more
stable than native ASNase but less stable than scFv-ASNase fusion. The results of
immunological assay indicated that the immunogenicity of the fusion proteins
increased while their binding capacity with the anti-ASNase serum decreased by
comparison to the native ASNase. Moreover, here the comparison of the basic
physical and chemical properties of the ASNase-scFv fusion, scFv-ASNase fusion,
and native ASNase is presented. Based on the structural evidence and the
biochemical analysis described in this paper, the protection mechanism proposed
in our previous study was further supported. The scFv moiety of the fusion
protein may confer the ASNase moiety resistance to proteolysis as a result of
both steric hindrance such as blocking the cleavage sites of trypsin and a change
in the electrostatic potential surface of the enzyme.
PMID- 11006105
TI - Glucocorticoid resistance in thymocytes from mice expressing a T cell receptor
transgene.
AB - A majority of thymocytes undergo apoptosis during differentiation due to lack of
survival signals provided by T cell receptor (TCR) activation. As glucocorticoids
(GC) have been suggested to be involved in this process, we have investigated the
GC sensitivity in thymocytes from mice expressing a transgenic selecting TCR. We
now report that immature CD4(+)CD8(+) double-positive thymocytes from these mice
are comparatively more resistant to corticosterone-induced apoptosis. This is
associated with reduced glucocorticoid receptor (GR) expression, increased levels
of membrane CD28, increased NF-kappaB DNA binding activity, and increased binding
to the CD28 response element in the interleukin-2 gene promoter. Analysis of NF
kappaB/Rel proteins from nuclear extracts demonstrated altered levels of some of
these proteins. Our results suggest that TCR recognition of self major
histocompatibility antigens generates intracellular signals which alter the
thymocyte GC sensitivity and thereby protect them against apoptosis induced by
endogenous GC.
PMID- 11006107
TI - Functional properties of sodium channels do not depend on the cytoskeleton
integrity.
AB - Several observations suggest an interaction of the sodium channel alpha-subunit
with the cytoskeletal structures. However, there is a wide variability in the
results of experiments of heterologous expression in Xenopus oocytes and studies
on mammalian cells are sometimes contradictory. In general, there has been no
direct demonstration that ad hoc large perturbations of the cytoskeleton modify
the intrinsic properties of the sodium channels expressed endogenously or
heterologously in plasma membranes. We have studied in CHO cells transfected with
the rat muscle sodium channel alpha-subunit the effects of two substances
expected to produce drastic perturbations of the cytoskeletal structure:
Cytochalasin-D, which depolymerizes microfilaments, and Colchicine, which
inhibits the microtubules polymerization. We observed no significant differences
in the voltage dependence, kinetic parameters and surface density of the
expressed sodium channels after treatment of the cells with these substances. We
conclude that the two known main components of the cytoskeleton do not interfere
directly with the sodium channel function or with the heterologous expression of
channels in the cell membrane.
PMID- 11006109
TI - Cysteine is the initial site of modification of alpha-crystallin by kynurenine.
AB - Tryptophan metabolites, such as kynurenine, are spontaneously unstable at neutral
pH. They undergo side-chain deamination yielding reactive alpha, beta unsaturated
ketones. In the lens, where these compounds act as UV filters, reaction of the
breakdown products with lens proteins (crystallins) may be largely responsible
for age-dependent colouration of this tissue. In previous research, where high pH
(pH 9) was used to promote deamination and conjugation with lens protein,
histidine, lysine, and cysteine residues were found to be modified. In this study
we show that, at pH 7, site of reaction with the major lens chaperone alpha
crystallin, is the single cysteine residue of the alphaA subunit. This apparent
selectivity has important ramifications because the cysteine-kynurenine adduct is
itself unstable under physiological conditions.
PMID- 11006108
TI - Evidence for the cluster model of mitochondrial steroid hydroxylase system
derived from dissociation constants of the complex between adrenodoxin reductase
and adrenodoxin.
AB - Using biotinylated adrenodoxin and avidin-Sepharose 4B, dissociation constants
for the complex between adrenodoxin reductase and adrenodoxin in the oxidized and
reduced states were determined as 50 +/- 11 and 296 +/- 44 nM, respectively.
Concentrations of adrenodoxin reductase/adrenodoxin in the matrix fraction from
bovine adrenal cortex, liver, and kidney mitochondria were determined to be 20.2
+/- 10.6 microM/120 +/- 23 microM, 0.17 +/- 0.06 microM/1.79 +/- 0.24 microM, and
0.40 +/- 0.23 microM/1.33 +/- 0.26 microM, respectively. The calculation of the
percentage of adrenodoxin reductase in the complex form in the reduced state
showed that it is higher than 99% in adrenal cortex mitochondria, providing clear
evidence for the cluster model for the mitochondrial steroid hydroxylase system.
PMID- 11006110
TI - Site-directed mutagenesis of the substrate-binding cleft of human estrogen
sulfotransferase.
AB - The sulfonation of estrogens by human estrogen sulfotransferase (humSULT1E1)
plays a vital role in controlling the active levels of these hormones in the
body. To understand more fully the structural and functional characteristics of
humSULT1E1, we have carried out site-directed mutagenesis of critical amino acids
found in the substrate-binding cleft. Three single amino acid mutations of
humSULT1E1 (V145E, H107A, and K85A) were created in this study. Kinetic studies
were used to provide information about the importance of these residues in
substrate specificity and catalysis, using a variety of substrates. Lysine at
position 85 has been proposed to be within hydrogen bonding distance to the
3alpha-phenol group of beta-estradiol, thereby stabilising the substrate in the
active site. However, substitution to a neutral alanine at this position improved
substrate specificity of humSULT1E1 for beta-estradiol, estrone, and
dehydroepiandrosterone (DHEA). The exchange of valine 145 for negatively charged
glutamic acid markedly improved the ability of humSULT1E1 to sulfonate dopamine,
but caused a reduction in specificity constants toward steroids tested, in
particular DHEA. The presence of a histidine residue at position 107 was shown to
be essential for the production of a functional protein, as substitution of this
amino acid to alanine resulted in complete loss of activity of humSULT1E1 towards
all substrates tested.
PMID- 11006111
TI - Equivalent death of P-glycoprotein expressing and nonexpressing cells induced by
the protein kinase C inhibitor staurosporine.
AB - P-glycoprotein (P-gp) is an ATP-dependent drug pump that confers multidrug
resistance. In addition to its ability to efflux toxins P-gp can also inhibit
apoptosis induced by a wide array of cell death stimuli that rely on activation
of intracellular caspases for full function. We have previously demonstrated that
stimuli including drugs such as hexamethylene bisacetamide (HMBA), the cytotoxic
lymphocyte granule protein granzyme B, and pore-forming proteins such as
perforin, kill P-gp positive cells in a caspase-independent manner. We therefore
hypothesised that drugs that are not effluxed by P-gp and which induce cell death
in the absence of caspase activation could induce death of P-gp expressing cells.
Staurosporine has been previously shown to kill cells in the absence of caspase
activation. Consistent with our hypothesis, we demonstrate here that
staurosporine can equivalently kill P-gp(+ve) and P-gp(-ve) tumor cell lines in a
caspase-independent manner.
PMID- 11006112
TI - Increase in X-ray-induced mutations by exposure to magnetic field (60 Hz, 5 mT)
in NF-kappaB-inhibited cells.
AB - It is established that extremely low frequency magnetic fields (ELFMF) at the
flux densities, i.e., 5 mT and less, are not mutagenic. However, exposure to
ELFMF enhances mutations induced by X-rays. In this study, we examined the
effects of long-term exposure to 5 mT ELFMF on mutation induction and X-ray
induced mutations in human malignant glioma cells (MO54) with different mutant
IkappaB-alpha (a critical inhibitor of NF-kappaB) genes. Cells were exposed or
sham-exposed to 5 mT ELFMF for up to 8 days with or without initial X-rays (4
Gy), and the mutant frequency of hypoxanthine-guanine phosphoribosyl transferase
(HPRT) gene was analyzed. An obvious increase in X-ray-induced mutations was
observed after treatment with ELFMF in combination with X-irradiation in MO54
cells with tyrosine mutant IkappaB-alpha gene other than with serine mutant
IkappaB-alpha gene or vector alone. Exposure to ELFMF alone increased mutations
significantly in MO54 cells with tyrosine mutant IkappaB-alpha gene. In addition,
X-ray-induced apoptoic cells were increased in MO54-V cells after exposure to
ELFMF, while an anti-apoptotic effect of magnetic field was found in MO54-SY4
cells. Our data suggest that exposure to 5 mT ELFMF may induce mutations and
enhance X-ray-induced mutations, resulting from the inactivation of NF-kappaB
through the inhibition of tyrosine phosphorylation.
PMID- 11006113
TI - Molecular cloning and chromosomal mapping of a novel five-span transmembrane
protein gene, M83.
AB - In an attempt to identify novel transmembrane molecules expressed on
hematopoietic cells, we identified a novel transmembrane protein gene, M83.
Cloning of the full-length cDNAs of human and mouse M83 revealed that M83 encodes
a type I transmembrane protein with a region containing five hydrophobic segments
within the C-terminal part of the protein, suggesting that M83 is a five-span
transmembrane molecule. The M83 protein was expressed on the cell surface as a
glycosylated protein with a molecular mass of 84 kDa. The M83 gene was localized
to human chromosome 16p13.3, mouse chromosome 17B1, and rat chromosome 10q12.3
distal. In human, M83 mRNA was highly expressed in placenta, pancreas, and
lymphohematopoietic tissues including peripheral blood, spleen, and bone marrow.
Among hematopoietic cells, it was highly expressed in resting T lymphocytes and
was downregulated by cell activation, suggestive of its biological role related
to the T cell resting status.
PMID- 11006114
TI - Peptide-mediated transcytosis of phage display vectors in MDCK cells.
AB - Delivery of therapeutic macromolecules and gene vectors to certain tissues is
hampered by endothelial or epithelial barriers. We show here that the transport
of phage particles across epithelial cells can be facilitated by peptide ligands
selected from a phage library of random peptides. Using MDCK cells, we identified
a polycationic peptide sequence, RYRGDLGRR, containing a putative integrin
binding (RGD) motif that enhanced basal-to-apical transcytosis of peptide-bearing
phage 1000- to 10,000-fold compared with phage with no peptide insert. Both the
synthetic peptide RYRGDLGRR and the integrin-binding peptide GRGDSP inhibited
phage transcytosis suggesting the involvement of integrins. Confocal
immunofluorescence microscopy showed that following internalization at the basal
cell surface, phage particles were delivered to the apical cytoplasm and released
at the apical cell surface. These data suggest the feasibility of using short
peptides for targeting transcytotic pathways and facilitating delivery of
macromolecules across cellular barriers.
PMID- 11006115
TI - Cloning, functional characterization, and expression of thyrotropin receptors in
the thyroid of amago salmon (Oncorhynchus rhodurus).
AB - Two thyrotropin receptor cDNAs (sTSH-Ra and sTSH-Rb) were cloned from thyroid
tissue of the amago salmon, Oncorhynchus rhodurus. sTSH-Ra and sTSH-Rb showed the
highest degrees of sequence homology to mammalian TSH receptors. Functional
characterization in COS-7 cells transiently transfected with sTSH-Ra or sTSH-Rb
showed the largest increase in cAMP when exposed to bovine TSH. RT-PCR analysis
demonstrated that sTSH-Ra and sTSH-Rb were expressed in the basibranchial region,
but not in the ovary, testis, liver, kidney or brain. In situ hybridization
revealed that sTSH-Ra and sTSH-Rb were exclusively expressed in thyroid
follicular epithelial cells of amago salmon undergoing smoltification. These
results indicated that the cloned cDNAs encode functional TSH receptor proteins.
This is the first report of isolation of TSH receptor molecules from nonmammalian
vertebrates.
PMID- 11006116
TI - Amplification and overexpression of TGIF2, a novel homeobox gene of the TALE
superclass, in ovarian cancer cell lines.
AB - Homeodomain transcription factors play important roles in directing cellular
proliferation and differentiation. A TALE-superclass homeodomain protein,
multifunctional repressor of TGFbeta-induced transcription. Here we report
identification of TGIF2, a novel TALE-superclass homeodomain protein that shows
distinct homology with TGIF, especially in its DNA-binding domain. TGIF2 is
expressed ubiquitously in human tissues, with the highest levels being found in
heart, kidney, and testis. The TGIF2 product contains a putative nuclear
localization signal; translocation of the protein to the nucleus was confirmed by
transfection of epitope-tagged cDNA. TGIF2 lies on chromosome 20q11.2-12. Since
amplification of 20q is often observed among ovarian cancers, we determined the
status of DNA copy-number and expression of TGIF2 in 14 ovarian-cancer cell
lines. This gene was over-expressed in all lines that showed amplification by
FISH analysis. The results suggested that TGIF2 may play an important role in the
development and/or progression of some ovarian tumors through a mechanism of gene
amplification.
PMID- 11006117
TI - Human CDK10 gene isoforms.
AB - The CDK10/PISSLRE gene has been shown to encode two different CDK-like putative
kinases. The function(s) of the gene products are unknown, although a role at the
G2/M transition has been suggested. We characterised two novel cDNAs. CDK10 mRNA
quantity was not found to be correlated with cell proliferation status in HeLa or
WI38 cell cultures or in human tissues. Relative levels of the four CDK10
isoforms were studied by RT-PCR, of which three were principally expressed. The
two initially cloned isoforms predominated in human tissues, except in brain and
muscle. Relative isoform levels did not vary during the cell cycle in culture,
except when cells entered into the cell cycle. Finally, the predominant isoforms
were shown to have different translation initiation sites and to have different
subcellular distribution, due to an alternatively spliced nuclear localisation
signal.
PMID- 11006118
TI - Norcantharidin-induced post-G(2)/M apoptosis is dependent on wild-type p53 gene.
AB - Norcantharidin (NCTD), a synthetic analogue of phosphatase type 2A inhibitors,
cantharidin, was shown to have limited effects in treating human and animal
tumors. The tumor cell killing mechanisms by norcantharidin, however, remain
unclear. In this report, we wished to investigate the mechanisms of
norcantharidin-mediated cytotoxicity. Effort was made to investigate whether
norcantharidin exerted its cytotoxicity through a p53-dependent or -independent
mechanism. RT-2 (wtp53) and U251 (mutant p53) glioblastoma cell lines were
exposed to norcantharidin at different dosages. Time-course fluorescent-activated
cell sorting (FACS) analysis showed that high doses of norcantharidin arrested
the cells at the G(2)/M phase and subsequent post-G(2)/M apoptosis in RT-2 cell
line. In comparison, the U251 cell line was found resistant to norcantharidin
induced cytotoxicity. Restoring wild-type p53 gene function in the U251 cell line
after adenoviral infections induced tumor cell cytotoxicity after exposure to
norcantharidin. These results showed that norcantharidin kills tumor cells
efficiently corresponding to their endogenous p53 gene status. The results also
showed the feasibility of using adenoviral p53 gene therapy to enhance
chemosensitivity of tumor cells to norcantharidin.
PMID- 11006119
TI - Molecular cloning of the crustacean DD4 cDNA encoding a Ca(2+)-binding protein.
AB - A cDNA, named DD4, was identified in the prawn Penaeus japonicus in a search for
genes that were expressed during calcification of the crustacean exoskeleton. DD4
transcripts were detected in the epidermal cells underlying the exoskeleton
specifically during the postmolt stage, when the calcification takes place. In
the DD4 cDNA an open reading frame of 542 amino acids was found. The deduced
protein was acidic and proline-rich, and exhibited similarity to the Drosophila
Ca(2+)-binding protein calphotin in the amino acid sequence and composition. The
DD4 cDNA was expressed in Escherichia coli to characterize Ca(2+)-binding of the
encoded protein, and Ca(2+) was found to bind to a central segment of 186 amino
acids. The DD4 protein is suggested to play a role in the calcification of the
crustacean exoskeleton.
PMID- 11006120
TI - Enzymatic modification of heparan sulfate on a biochip promotes its interaction
with antithrombin III.
AB - A heparan sulfate glycosaminoglycan chain, biotinylated at its reducing-end, was
bound to a streptavidin-coated biochip. Surface plasmon resonance spectroscopy
showed a low affinity interaction with antithrombin III (ATIII) when it was
flowed over a surface containing heparan sulfate. ATIII bound tightly with high
affinity when the same surface was enzymatically modified to using 3-O
sulfotransferase isoform 1 (3-OST-1) in the presence of 3'-phosphoadenosine 5'
phosphosulfate (PAPS). The 3-OST-1 enzyme is involved in heparan sulfate
biosynthesis and introduces a critical 3-O-sulfo group into this
glycosaminoglycan affording the appropriate pentasaccharide sequence capable of
high affinity binding to ATIII. This experiment demonstrates the specific
structural modification of a glycosaminoglycan bound to a biochip using a
biosynthetic enzyme, suggesting a new approach to rapid screening
glycosaminoglycan-protein interactions.
PMID- 11006121
TI - A novel form of gonadotropin-releasing hormone in the medaka, Oryzias latipes.
AB - The present study has identified three molecular forms of gonadotropin-releasing
hormone (GnRH) in the brain of a teleost, the medaka, by isolation of their
cDNAs. This species has a novel GnRH, which is here named medaka-type GnRH
(mdGnRH), in addition to two characterized forms, chicken-II-type GnRH (cGnRH-II)
and salmon-type GnRH (sGnRH). Phylogenetic analysis showed that mdGnRH is a
medaka homolog of and seabream-type GnRH (sbGnRH) and mammalian-type GnRH (mGnRH)
in other species, and suggested that all vertebrates have three distinct GnRHs.
Furthermore, in situ hybridization revealed that the mdGnRH gene is expressed
only in neurons clustered within the preoptic area as sbGnRH and mGnRH genes in
other species are, while the genes for cGnRH-II and sGnRH are only in the
midbrain tegmentum and nucleus olfactoretinalis, respectively. This result
suggested that mdGnRH is a hypophysiotropic factor and the other two forms are
involved in other physiological events as neuromodulators or neurotransmitters.
PMID- 11006122
TI - Biological characterization of uncleavable plasma membrane-anchored human
macrophage colony-stimulating factor.
AB - The cell-surface form of human macrophage colony-stimulating factor (CSF-1(256),
M-CSFalpha) is a plasma membrane-anchored transmembrane protein from which the
soluble CSF-1 is released by ectodomain proteolytic cleavage. We have previously
generated two forms of cell surface CSF-1 which failed to undergo the cleavage by
deleting residues 161-165 or residues 159-165 in the extracellular juxtamembrane
region (1). To determine the biologic significance of the ectodomain cleavage, we
compared the biosynthesis and biologic activities of uncleavable mutant CSF-1
forms with those of the cleavable wild-type (WT) CSF-1. We found that the
uncleavable CSF-1 forms were able to accumulate on cell surface at about
threefold higher level than the cleavable WT CSF-1 did. We further demonstrated
that the uncleavable plasma membrane-anchored forms of CSF-1 were biologically
active in mediating the proliferation of CSF-1-dependent cells as well as the
intercellular adhesion between CSF-1 receptor-bearing cells and CSF-1 expressing
cells. Furthermore, the adhesive activity of uncleavable CSF-1 forms was about
twofold stronger than that of WT CSF-1, which indicated that the ectodomain
cleavage system plays an important role in regulating the biologic activities of
membrane-anchored CSF-1.
PMID- 11006123
TI - An anion channel in guinea pig gallbladder epithelial cells is highly permeable
to HCO(-)(3).
AB - In guinea pig gallbladder epithelium, a secretion of fluid, secondary to an
electrogenic secretion of Cl(-) and HCO(-)(3), is elicited in the presence of a
high intracellular concentration of adenosine 3'-5'-cyclic monophosphate (cAMP).
The aim of this study was to analyze the effects of secretagogues on the activity
of anionic channels in isolated epithelial cells using the patch-clamp technique
and measuring the electrical potential difference of the cellular membrane
(pd(cm)). In cell-attached configuration, with the microelectrode filled with a
solution of N-methylglucamine-Cl, or in inside-out configuration (symmetrical
solution), it was possible to demonstrate the presence of an 18-pS Cl(-) channel
with linear current/voltage (I/V) relationship and voltage independence; this
channel is not activated by cAMP (cell-attached configuration). In inside-out
configuration (symmetrical solution), another anionic channel with a conductance
of 2.8 pS, voltage independence, and a linear I/V relationship was also
identified. This channel was stimulated by cAMP (cell-attached configuration) and
by PKA + ATP + cAMP (inside-out configuration). The channel was inhibited by NPPB
(10(-5) M), but not by other anionic inhibitors. Measurements of the pd(cm) value
suggested that in isolated cells, as in whole tissue, cAMP activates conductance
for both Cl(-) and HCO(-)(3). The selectivity of the channel was gluconate < SO(2
)(4) < Cl(-) < Br(-) < I(-) < HCO(-)(3) < SCN(-) and the P(HCO(3))/P(Cl) was 2.6.
Some features of the channel resemble those of the cystic fibrosis transmembrane
conductance regulator (CFTR) chloride channel and RT-PCR performed on mRNA from
isolated epithelial cells detected the presence of a CFTR homologue mRNA. The
results obtained indicate that this channel is responsible for the HCO(-)(3)
conductance activated by cAMP.
PMID- 11006124
TI - Hypoxia induces the expression of a 43-kDa protein (PROXY-1) in normal and
malignant cells.
AB - This study was designed to determine the expression of cellular factors that may
participate in phenotypic changes that occur under conditions of hypoxia. Using
the RT-PCR differential display method, we isolated a cDNA fragment corresponding
to a gene whose expression was induced in trophoblast and breast carcinoma cells
cultured under 1 or 2% oxygen vs 4% oxygen or higher. This gene encodes a 43-kDa
protein initially identified in homocysteine-treated endothelial cells and later
shown to be upregulated in various human and mouse cell types (termed RTP, Drg1,
Cap43, rit42, Ndr1). Herein we refer to this gene product as PROXY-1, for Protein
Regulated by OXYgen-1. Elevated mRNA and protein levels were first observed in
cells cultured in 1% oxygen for 8 h. Although PROXY-1 mRNA levels returned to
near-control values within 2 h of reexposure to 20% oxygen, protein levels
remained high 72 h after reexposure to 20% oxygen. Treatment of cells with
hypoxia mimics such as cobalt or iron chelators also increased PROXY-1
expression. Moreover, presence of 30% carbon monoxide in the hypoxic atmosphere
abrogated the upregulation of PROXY-1 expression. These findings suggest that
hypoxia upregulates PROXY-1 levels through a heme protein-dependent pathway and
that assessment of PROXY-1 expression may be of potential use in evaluating
tissue hypoxia.
PMID- 11006125
TI - Neuroendocrine-specific protein C, a marker of neuronal differentiation, is
reduced in brain of patients with Down syndrome and Alzheimer's disease.
AB - Neuroendocrine-specific protein C (NSP-C) is found in neural and neuroendocrine
cells and associated with the endoplasmic reticulum. Its expression was found to
correlate with the degree of neuronal differentiation. As the neuropathological
findings in Down syndrome (DS) includes deficits of differentiation, and we
detected a downregulated sequence with 100% homology with NSP-C homolog mRNA in
temporal cortex of patients with DS as well as Alzheimer's disease (AD) using
differential display-polymerase chain reaction (DD-PCR), we decided to examine
the protein levels of NSP-C in temporal, frontal cortex and cerebellum of DS and
AD. To normalize NSP-C versus neuronal density, we also determined neuron
specific enolase (NSE) levels and calculated the ratios. NSP-C was significantly
reduced in DS (temporal and frontal cortex) and AD (frontal cortex) compared to
controls. The significant decrease of NSP-C in DS was even more pronounced when
related to NSE levels. Impaired differentiation in DS brain may well be due to
absolutely and relatively decreased NSP-C levels in temporal and frontal cortex.
As NSP-C was also reduced in AD frontal cortex, NSP-C deficits in these disorders
may be reflecting neurodegenerative changes rather than a primary and specific
finding of DS or AD pathogenesis.
PMID- 11006126
TI - Identification and characterization of rat AILIM/ICOS, a novel T-cell
costimulatory molecule, related to the CD28/CTLA4 family.
AB - Activation-inducible lymphocyte immuno-mediatory molecule (AILIM) is an inducible
cell surface glycoprotein expressed on thymocytes and activated lymphocytes.
Specific monoclonal antibody to rat AILIM induced the cell aggregation of a rat
thymoma cell line and ConA-activated splenocytes. In the present study, we
identified the primary structure of two species of rat AILIM by expression
cloning. We also cloned mouse and human AILIM homologues and the predicted amino
acid sequences were identical to those of the inducible costimulator ICOS/CRP-1,
which belongs to the CD28/CTLA4 family. Although the human and mouse AILIM/ICOS
molecule is localized on T-cells, the major population of AILIM/ICOS-positive
cells in rat splenocyte was CD45RA-positive B-cells. The expression level of
AILIM/ICOS on T-cells was relatively low; however, its expression was drastically
induced by the treatment with PMA plus Ca-ionophore or the engagement of CD3 and
these costimulatory molecules. Almost all T-cells exhibited potency as to its
expression. Functional analysis of AILIM/ICOS demonstrated that AILIM-mediated
costimulation was relatively weak compared to that of human.
PMID- 11006127
TI - Enhancement of the activity of l-aspartase from Escherichia coli W by directed
evolution.
AB - l-Aspartase was modified by directed evolution. After four rounds of error-prone
PCR and three rounds of DNA shuffling, an evolved enzyme purified from the final
round showed a 28-fold increased k(cat)/K(m) and 4.6-fold decreased K(m). The
thermostability and stable pH range were also enhanced. The DNA sequence of the
evolved aspartase gene showed seven base changes, resulting in three amino acid
changes from the native enzyme: N217K, T233R, V367G. The mechanism of the
enhancement of activity was analyzed.
PMID- 11006128
TI - Receptor isoform-specific interaction of prostaglandin EP3 receptor with
muskelin.
AB - By using the yeast two-hybrid system, muskelin was found to bind with the carboxy
terminal tail of the prostaglandin EP3 receptor alpha isoform but not with either
the beta or gamma isoform. A direct interaction between the carboxy-terminal tail
of the alpha isoform and muskelin was confirmed in vitro using recombinant fusion
proteins. Analysis by confocal microscopy indicated that the isoform and muskelin
were distributed at the plasma membrane in transfected cells. When the isoform
was stimulated by agonist, the receptor was internalized in the cells expressing
the receptor alone, but this internalization was partially inhibited by the
cotransfection with muskelin. Furthermore, muskelin enhanced the Gi activity of
the isoform. Thus, muskelin appears to be an isoform-specific anchoring protein
for the EP3 receptor.
PMID- 11006129
TI - Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 ubiquitin
ligase activity.
AB - Mutations of the von Hippel-Lindau (VHL) tumor suppressor gene predispose
individuals to a variety of human tumors, including renal cell carcinoma,
hemangioblastoma of the central nervous system, and pheochromocytoma. Here we
report on the identification and characterization of the Drosophila homolog of
VHL. The predicted amino acid sequence of Drosophila VHL protein shows 29%
identity and 44% similarity to that of human VHL protein. Biochemical studies
have shown that Drosophila VHL protein binds to Elongins B and C directly, and
via this Elongin BC complex, associates with Cul-2 and Rbx1. Like human VHL,
Drosophila VHL complex containing Cul-2, Rbx1, Elongins B and C, exhibits E3
ubiquitin ligase activity. In addition, we provide evidence that hypoxia
inducible factor (HIF)-1alpha is the ubiquitination target of both human and
Drosophila VHL complexes.
PMID- 11006130
TI - Upregulation of the apoptosis-associated protein Grb3-3 in HIV-1-infected human
CD4(+) lymphocytes.
AB - The mechanism(s) by which HIV-1 infection contributes to depletion of CD4(+) T
cell is not well understood. In this report, we investigated whether a recently
identified isoform of growth factor receptor bound protein (Grb2), named Grb3-3,
a signaling molecule that is associated with the MAP kinase pathway and with
apoptosis could be involved. We find that Grb3-3 is markedly up-regulated
following HIV-1 infection of CD4(+) peripheral blood mononuclear cells undergoing
apoptosis. Although IL-2 deprived CD4(+) cells also undergo apoptosis to a
similar extent, Grb3-3 upregulation is not detected under these experimental
conditions. Transient overexpression of Grb3-3 in Jurkat T-cells also causes
apoptosis. Upon staurosporine stimulation, Grb3-3 predisposes Sup-T1 cell to
apoptosis. Finally, analysis of the HIV-1 genes responsible for Grb3-3 expression
demonstrates that Tat and Nef can independently induces its expression,
suggesting these two earliest viral gene products of HIV-1 may share some common
pathway(s) in up-regulating Grb3-3 expression.
PMID- 11006131
TI - Anti-angiogenic potential of a cancer chemopreventive flavonoid antioxidant,
silymarin: inhibition of key attributes of vascular endothelial cells and
angiogenic cytokine secretion by cancer epithelial cells.
AB - In recent studies, we have shown that silymarin, a naturally occurring flavonoid
antioxidant, exhibits anti-cancer effects against several epithelial cancers.
Here, we assessed its potential as an anti-angiogenic agent employing human
umbilical vein endothelial cells (HUVEC) and human prostate and breast cancer
epithelial cells. When sub-confluent HUVEC were treated for 48 h, adherent cell
number decreased by 50 and 90% at 50 and 100 microg/ml doses, respectively.
Apoptotic cell death principally accounted for cell loss at >50 microg/ml doses.
In biochemical analysis, silymarin treatment of HUVEC for 6 h resulted in a
concentration-dependent decrease in the secretion and cellular content of matrix
metalloproteinase (MMP)-2/gelatinase A. Silymarin also inhibited HUVEC tube
formation (in vitro capillary differentiation) on a reconstituted extracellular
matrix, Matrigel. In other studies, 5 to 6 h exposure of DU145 prostate, and MCF
7 and MDA-MB-468 breast cancer cells to silymarin resulted in a dose-dependent
decrease in the secreted vascular endothelial growth factor (VEGF) level in
conditioned media without any visible change in cell morphology. The inhibitory
effect of silymarin on VEGF secretion occurred as early as 1 h. These
observations indicate a rapid inhibitory action of silymarin on the secretion of
this primary angiogenic cytokine by cancer epithelial cells. Taken together, the
results of this study support the hypothesis that silymarin possesses an anti
angiogenic potential that may critically contribute to its cancer chemopreventive
efficacy.
PMID- 11006132
TI - The endogenous oxindoles 5-hydroxyoxindole and isatin are antiproliferative and
proapoptotic.
AB - Oxindole-core synthetic molecules are currently being developed as anticancer
drugs that target protein tyrosine kinases associated with growth factor
receptors. Oxindole, 5-Hydroxyoxindole, and 2, 3-dioxindole [isatin] are natural
molecules found in mammalian body fluids and tissues and we addressed the
question of similar properties of endogenous oxindoles. 5-Hydroxyoxindole and
isatin, but not oxindole, inhibited N1E-115, BALB/c3T3, BBC, PC12, and HL60
proliferation at submicromolar concentrations. Acute treatment with 5
hydroxyoxindole and isatin reduced the activity of extracellular signal regulated
protein kinases (ERKs) by 35% at 100 microM and ERK1 activity was strongly
inhibited by 5-Hydroxyoxindole at 10 microM. Survival of PMA-differentiated HL60
and FGF(2)-differentiated PC12 cells was not affected by 5-Hydroxyoxindole and
isatin treatment, suggesting that endogenous oxindoles interact with growth
factors signaling. The physiological implications of these data and the potential
utility of 5-Hydroxyoxindole and isatin as antitumor agents are discussed.
PMID- 11006133
TI - Physical interaction of Delta1, Jagged1, and Jagged2 with Notch1 and Notch3
receptors.
AB - The Delta/Serrate/LAG-2 (DSL) domain-containing proteins, Delta1, Jagged1, and
Jagged2, are considered to be ligands for Notch receptors. However, the physical
interaction between the three DSL proteins and respective Notch receptors
remained largely unknown. In this study, we investigated this issue through the
targeting of Notch1 and Notch3 in two experimental systems using fusion proteins
comprising their extracellular portions. Cell-binding assays showed that soluble
forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on
the cell surface. In solid-phase binding assays using immobilized soluble Notch1
and Notch3 proteins, it was revealed that each DSL protein directly bound to the
soluble Notch proteins with different affinities. All interactions between the
DSL proteins and soluble Notch proteins were dependent on Ca(2+). Taken together,
these results suggest that Delta1, Jagged1, and Jagged2 are ligands for Notch1
and Notch3 receptors.
PMID- 11006134
TI - Farnesyl transferase inhibitors: current developments and future perspectives.
AB - Ras oncogenes play an important role in carcinogenesis and are frequently found
in various human tumour types. Cellular activity of Ras oncoprotein, regulated
through the enzyme farnesyl transferase, is crucial in the process of ras
dependent carcinogenesis, and therefore, specific inhibition of this enzyme is an
attractive goal in anticancer treatment. Specific inhibitors of farnesyl
transferase have been developed in recent years, many of them showing in vitro
and in vivo growth inhibitory or cytostatic activity. Recently, results of the
first clinical studies with various farnesyl transferase inhibitors have been
presented. In the design of phase I and II studies, either single-agent or
combination studies, new endpoints have to be defined in order to properly assess
feasibility, antitumour activity and clinical valuability.
PMID- 11006135
TI - Antisense therapy in cancer.
AB - This review discusses laboratory and clinical studies of antisense
oligodeoxynucleotides as potential treatments for haematological malignancies and
solid tumours. Mechanisms of action, pharmacokinetics, toxicities and potential
clinical applications of these agents are described.
PMID- 11006136
TI - A review of angiogenesis and antiangiogenic therapy with thalidomide in multiple
myeloma.
AB - Angiogenesis is the formation of new blood vessels and occurs physiologically
during embryonal growth, wound healing and during the menstrual cycle. It is
essential for the proliferation and metastases of most malignant neoplasms.
Recent evidence suggests that angiogenesis is increased in multiple myeloma and
has prognostic value in the disease. Angiogenic cytokines such as vascular
endothelial growth factor (VEGF) and basic fibroblast growth factor are expressed
by myeloma cells and appear to play a role in the increased angiogenesis seen in
myeloma. In addition, VEGF may serve as a paracrine growth factor for myeloma
cells. Based on the increased angiogenesis observed in myeloma, thalidomide has
been studied as antiangiogenic therapy. Although its mechanism of action in
myeloma is still unclear, thalidomide appears to be active in 25-30% of patients
with refractory myeloma. Major toxicities include constipation, sedation, skin
rash, fatigue, and peripheral neuropathy. Studies are ongoing to determine its
role as initial treatment for myeloma. This paper reviews the available data on
angiogenesis in myeloma, and summarizes the role of thalidomide therapy in this
disease. The pharmacology and toxicity of thalidomide are also discussed.
PMID- 11006137
TI - The effect of chemotherapy on the growing skeleton.
AB - With the increasing use of high dose (poly)chemotherapy schedules in the
treatment of childhood cancer it is particularly important to know the adverse
effects of these treatments. Growth is a complex mechanism affected not only by
chemotherapy but also by the malignancy itself as well as nutritional status, the
use of corticosteroids and (cranial) radiation. In vitro and animal studies are
often the most useful in determining the effect of a single chemotherapeutic
agent on the growing skeleton. In vitro studies have shown doxorubicin,
actinomycin D and cisplatin to have a direct effect on growth plate chondrocytes
that in animals results in decreased growth and final height. Clinical studies
with multiagent chemotherapy have demonstrated that antimetabolites decrease bone
growth and final height. Childhood cancer survivors are at risk of a reduced bone
mineral density, mainly due to methotrexate, ifosfamide and corticosteroids. This
reduced bone mineral density persists into adult life and may increase bone
fracture risk at an older age.
PMID- 11006139
TI - Articles to appear in forthcoming issues of cancer treatment reviews
PMID- 11006138
TI - Treatment-related leukaemia--a clinical and scientific challenge.
AB - The development of a second tumour, including treatment-related leukaemia (TRL),
is the most devastating complication of intensive cancer chemotherapy. This is
especially relevant in the paediatric population as over 70% of children
diagnosed with a malignancy will now live at least 5 years. Most TRLs are myeloid
leukaemias and carry an overall poor prognosis when compared with their de novo
counterparts. Despite the well known association with specific cytotoxic agents,
improved understanding of the pathogenesis and risk factors of TRL is ultimately
essential if we are to develop successful strategies for prevention and
treatment. Here we review these aspects, together with the clinical and diverse
biological features of this complication and the efficacy of current therapy.
PMID- 11006140
TI - Metabolic factors affecting the reproductive axis in male sheep.
AB - Changes in food intake affect the reproductive axis in both sexes, and the
nutritional signals involved and the sites that receive those signals are now
beginning to be unravelled. Our studies have focussed on the mature male sheep, a
model in which high food intake stimulates GnRH-LH pulse frequency for only 10-20
days but continues to promote testicular growth over several months. Different
signals and different target organs seem to be responsible for these short- and
long-term responses. Short-term dietary treatments lead to changes in blood
concentrations of glucose, fatty acids, insulin and leptin, and concentrations of
glucose, insulin, leptin and some amino acids in cerebrospinal fluid. It seems
unlikely that amino acids affect GnRH-LH secretion directly in sheep.
Intracerebroventricular infusions of insulin specifically increase LH pulse
frequency, but intravenous, intra-abomasal or intracerebroventricular infusions
of glucose have no effect, despite their effects on cerebrospinal fluid insulin
concentrations. The addition of fatty acids to the diet also increases LH pulse
frequency, but does not affect the concentrations of insulin or leptin in the
cerebrospinal fluid. It appears that acute responses to changes in nutrition
involve a range of alternative pathways, possibly including interactions among
insulin, leptin and energy substrates. Effects of long-term dietary treatments on
testicular size are only partly dependent on the GnRH-LH system (that is, on
brain control) and so must also depend on other, as yet unknown, pathways.
Concepts of 'metabolic sensing and integration' are being developed from the
basis of existing knowledge of the central control of appetite and reproduction.
PMID- 11006141
TI - Effect of efferent duct ligation on the function of the blood-testis barrier in
rats.
AB - The function of the blood-testis barrier has been assessed from the ratio of the
Cr-EDTA space in the parenchyma to the measured interstitial volume in the testes
of rats at various times after unilateral ligation of the efferent ducts. The
barrier remained effective during the phase of fluid accumulation and testicular
mass gain, which was linear for at least 24 h, but the testis mass began to
decrease between 32 and 40 h after efferent duct ligation, and the Cr-EDTA space
at 40 and 48 h after efferent duct ligation exceeded the volume of the
interstitial tissue. This finding indicated that, at these times, the barrier to
Cr-EDTA, which is normally excluded from the tubules, had broken down and the
marker was entering the tubules. Thereafter, the Cr-EDTA space decreased again to
be less than the interstitial tissue volume, indicating a restoration of the
barrier function, although degeneration of the seminiferous epithelium continued
to become more obvious. The present study is the first report of a reversible
breakdown of the barrier, but the relevance of the breakdown to the effects on
spermatogenesis requires further study.
PMID- 11006142
TI - Effectiveness of zona pellucida protein ZPB as an immunocontraceptive antigen.
AB - Immunization of female mammals with native zona pellucida (ZP) proteins is known
to cause infertility. Since each human ZP protein is now available as a purified
recombinant protein, is it possible to compare the immunocontraceptive potential
of each ZP protein. A breeding study was conducted in cynomolgus monkeys (Macaca
fasicularis) after immunization with recombinant human ZP (rhZP) proteins (ZPA,
ZPB, ZPC) separately and in combinations. This study demonstrated that
immunization with recombinant human ZPB (rhZPB) protein caused cynomolgus monkeys
to become infertile for 9-35 months. A second study was conducted in baboons
(Papio cynocephalus), which yielded a similar result. The baboons immunized with
rhZPB became infertile for 9 to > 20 months. During the time of maximum antibody
titre, some animals experienced disruption of the menstrual cycle, but eventually
all of the animals resumed normal menstrual cycles. Control animals and animals
immunized with other rhZP proteins all became pregnant before any of the rhZPB
treated animals. This is the first study in which a recombinant ZP protein has
consistently induced infertility in a primate without permanent disruption of the
normal menstrual cycle.
PMID- 11006143
TI - Immunohistochemical localization of prostaglandin G/H synthase 1 and 2 in sheep
placenta after glucocorticoid-induced and spontaneous labour.
AB - Enhanced prostaglandin production and release by the placenta is an essential
element in the normal transition to labour in many animal species. In sheep,
expression of prostaglandin G/H synthase (PGHS) is the central enzyme regulating
this process. In this study immunohistochemistry was used to examine the
distribution of cells expressing PGHS-1 and PGHS-2 in ovine placenta in
association with spontaneous parturition (n = 6) and glucocorticoid-induced
labour (n = 5). Labour was induced in ewes after the intrafetal injection of
betamethasone on day 131 of gestation. Animals administered an intrafetal
injection of isotonic saline (n = 5) acted as non-labour controls. In placentomes
collected from all groups, immunoreactive PGHS-1 was present in the mononuclear
trophoblast cells of the fetal placenta. Cells in the maternal mesenchyme and
epithelial syncytium were weakly immunopositive for this enzyme. PGHS-1
immunoreactivity was also demonstrated in the endothelial cells of the chorionic
vessels. The PGHS-2 isozyme was localized exclusively to the trophoblast
epithelial cells. Immunoreactive PGHS-2 was not detectable in the maternal
epithelial syncytium or the stroma of the cotyledons. The binucleate cells of the
fetal placenta were consistently immunonegative for both PGHS isozymes. These
results indicate that the cellular localization of PGHS-1 and PGHS-2 in ovine
placenta does not change during the last 15 days of pregnancy. Co-localization of
these isozymes indicates that the source of arachidonic acid and the site of
prostanoid formation are the same. Quantitation of the percentage area of
positive staining for PGHS-1 and PGHS-2 using image analysis software
demonstrated a significant increase in PGHS-2 in the fetal trophoblast after
glucocorticoid-induced labour and spontaneous parturition. This finding indicates
that increased formation of the PGHS-2 isozyme is responsible for the large
increase in prostaglandin production by the ovine placenta at term labour.
PMID- 11006144
TI - Successful capacitation and homologous fertilization in vitro in Calomys
musculinus and Calomys laucha (Rodentia - sigmodontinae).
AB - Small South American rodents of the genus Calomys have been used extensively for
virology and ecological research. Previous studies have demonstrated that Calomys
musculinus and Calomys laucha have a relatively short oestrous cycle and that
superovulation and parthenogenetic activation can be induced. The purpose of this
study was to determine the requirements for in vitro manipulation of the male
gamete and in vitro fertilization. Two culture media and different concentrations
of spermatozoa were tested for their ability to support sperm motility,
hyperactivation and the acrosome reaction. The ability of capacitated Calomys
spermatozoa to penetrate zona-free hamster eggs was also evaluated. In vitro
fertilization was assessed by examining attachment and binding to the zona
pellucida, second polar body extrusion, pronucleus formation and the fertilizing
sperm tail. The results of the study showed that: (i) Tyrode's albumin lactate
pyruvate (TALP) medium was more effective than T6 medium for maintaining sperm
motility in vitro; (ii) hyperactivation was achieved with TALP but not with T6;
(iii) the acrosome reaction was easily distinguished by light microscopy and
depends on time and sperm concentration; (iv) capacitated spermatozoa are able to
penetrate zona-free hamster eggs; and (v) superovulated oocytes can be fertilized
in vitro. This is the first report of capacitation and in vitro fertilization for
Calomys sp. These results provide opportunities to use C. musculinus and C.
laucha as new laboratory animals for research into reproductive biology.
PMID- 11006145
TI - Studies of the oestrous cycle, oestrus and pregnancy in the koala (Phascolarctos
cinereus).
AB - As an integral part of the development of an artificial insemination programme in
the captive koala, female reproductive physiology and behaviour were studied. The
oestrous cycle in non-mated and mated koalas was characterized by means of
behavioural oestrus, morphology of external genitalia and changes in the
peripheral plasma concentrations of oestradiol and progestogen. The mean (+/-
SEM) duration of the non-mated oestrous cycle and duration of oestrus in 12
koalas was 32.9 +/- 1.1 (n = 22) and 10.3 +/- 0.9 (n = 24) days, respectively.
Although the commencement of oestrous behaviour was associated with increasing or
high concentrations of oestradiol, there were no consistent changes in the
morphology or appearance of the clitoris, pericloacal region, pouch or mammary
teats that could be used to characterize the non-mated cycle. As progestogen
concentrations remained at basal values throughout the interoestrous period, non
mated cycles were considered non-luteal and presumed anovulatory. After mating of
the 12 koalas, six females gave birth with a mean (+/- SEM) gestation of 34.8 +/-
0.3 days, whereas the remaining six non-parturient females returned to oestrus
49.5 +/- 1. 0 days later. After mating, oestrous behaviour ceased and the
progestogen profile showed a significant increase in both pregnant and non
parturient females, indicating that a luteal phase had been induced by the
physical act of mating. Progestogen concentrations throughout the luteal phase of
the pregnant females were significantly higher than those of non-parturient
females. Parturition was associated with a decreasing concentration of
progestogen, which was increased above that of basal concentrations until 7 days
post partum.
PMID- 11006146
TI - Natural and artificial methods for inducing the luteal phase in the koala
(Phascolarctos cinereus).
AB - An experiment was conducted in which female koalas were mated for different
durations of intromission and ejaculation to confirm that the luteal phase of the
oestrous cycle in koalas is induced by the physical act of mating. Results showed
that induction of a luteal phase in the koala usually required a complete
duration of penile thrusting behaviour from the male. It is proposed that
induction of a luteal phase in koalas may involve a copuloceptive reflex,
triggered by the thrusting of the male's penis into the female's urogenital
sinus. Although interrupted mating in koalas may be used to induce a luteal phase
in preparation for an artificial insemination programme, this study showed that
there is a 12.5% probability that pregnancy will result from semen prematurely
emitted by the teaser male. A dose of 250 iu hCG was administered intramuscularly
to eight oestrous females to determine whether it was possible to induce a luteal
phase artificially. In contrast to control females, which received sterile saline
injections, all females injected with hCG showed a significant increase in
progestogen concentration above that of basal values, indicating that a luteal
phase had been induced successfully.
PMID- 11006147
TI - Potential role of alphav and beta1 integrins as oocyte adhesion molecules during
fertilization in pigs.
AB - Integrin molecules are cell adhesion molecules that are thought to be involved in
sperm-oocyte interaction in rodents and humans. The objective of this study was
to evaluate whether integrin molecules were present on the surface of pig
oocytes, consistent with involvement in sperm-oocyte interaction in this species.
Immunocytochemistry and confocal microscopy were used to evaluate the presence of
beta1, and alpha1, alpha2, alpha3, alpha4, alpha5, alpha6 and alphav integrin
subunits on the plasma membrane of pig oocytes. The beta1 and alphav integrin
subunits were present consistently at the surface of pig oocytes; however, the
remaining alpha integrin subunits evaluated were not routinely detected. The
antibodies to the beta1 and alphav integrin subunits recognized appropriately
sized protein bands on western blots of partially purified oocyte plasma
membrane. These two antibodies also recognized oocyte plasma membrane protein
isolated from a sperm plasma membrane affinity column. Sperm plasma membrane
proteins of 137 and 93 kDa appeared to be the ligands for the beta1 integrin
subunit as revealed by a western sandwich blot. Antibody to an extracellular
domain of the beta1 integrin subunit reduced pig sperm-oocyte binding (P < 0.05),
also indicating an assisting role for a beta1 oocyte integrin subunit in sperm
oocyte interaction in pigs. These results are consistent with an alphavbeta1 pig
oocyte integrin interacting with a ligand on the sperm plasma membrane during
fertilization.
PMID- 11006148
TI - Production of tissue inhibitors of metalloproteinases (TIMPs) by pig ovarian
cells in vivo and the effect of TIMP-1 on steroidogenesis in vitro.
AB - Precisely which ovarian cells produce tissue inhibitors of metalloproteinases
(TIMPs) is unclear. Although granulosa cells are reported to produce TIMPs,
thecal TIMP production has not been investigated nor has the influence of TIMPs
on theca cells. Furthermore, although periovulatory follicles have been examined,
little is known about smaller ovarian follicles. Follicles >/= 2 mm in diameter
were collected from Large White hybrid gilts on the day before predicted oestrus
(n = 3) or after hCG treatment (n = 3) and divided into 1 mm size classes. Small
(2 to < 5 mm) follicles were kept intact, whereas follicles >/= 5 mm were
separated into follicular fluid, granulosa and theca cell compartments. After
homogenization, TIMP-1, -2 and -3 were detected by reverse zymography. Theca
cells (50 x 10(3) per well) were cultured with TIMP-1 (10, 100 or 200 ng ml(-1)
with or without long-R3 insulin-like growth factor I (IGF-I)) in a serum-free
system to investigate the effect on steroidogenesis and the number of cells. Both
large and small pig follicles produced TIMPs and TIMP-1, -2 and -3 were detected
in follicular fluid, granulosa and theca cell samples. There was a phase x tissue
type interaction for the presence of both TIMP-1 and -2 (P < 0.03, P < 0.05,
respectively), and TIMPs were detected in more granulosa and theca cell samples
after hCG than during the follicular phase. The concentrations were influenced by
the type of tissue (TIMP-1, P < 0.005; TIMP-2, P < 0.005, TIMP-3, P > 0.05), and
the highest concentrations occurred in the theca tissue. There were tissue type x
follicle size interactions for the presence of both TIMP-1 and -2 (P < 0.001). In
vitro, TIMP-1 increased thecal steroidogenesis after 144 h (oestradiol, P < 0.05,
progesterone, P < 0.001) but reduced the number of viable cells (P < 0.001). In
conclusion, TIMP-1, -2 and -3 were present in large and small pig follicles and
were produced by both granulosa and theca cells, although concentrations differed
with the type of tissue. Production was regulated by factors including follicle
size and phase of the oestrous cycle. In addition to controlling tissue
remodelling, TIMP-1 may also regulate steroidogenesis.
PMID- 11006149
TI - Immediate and delayed effects of heat stress on follicular development and its
association with plasma FSH and inhibin concentration in cows.
AB - The aim of this study was to characterize the immediate effects of heat stress on
plasma FSH and inhibin concentrations, and its involvement in follicular dynamics
during a complete oestrous cycle, and to examine a possible delayed effect of
heat stress on follicular development. Holstein dairy cows were oestrous
synchronized and randomly assigned to either cooled (n = 7) or heat-stressed (n =
6) treatment groups. During a complete oestrous cycle, control cows, which were
cooled, maintained normothermia, whereas heat-stressed cows, which were exposed
to direct solar radiation, developed hyperthermia. At the end of this oestrous
cycle (treated cycle), both groups were cooled and maintained normothermia for
the first 10 days of the subsequent oestrous cycle. Throughout this period,
follicular development was examined by ultrasonography, and plasma samples were
collected. During the second follicular wave of the treated oestrous cycle, a
significantly larger cohort of medium sized follicles (6-9 mm) was found in heat
stressed cows than in cooled cows (P < 0.05). The enhanced growth of follicles in
this wave in heat-stressed cows was associated with a higher plasma FSH increase
which lasted 4 more days (days 8-13 of the oestrous cycle; P < 0.05), and
coincided with a decrease in the plasma concentration of immunoreactive inhibin
(days 5-18 of the oestrous cycle; P < 0.05). During the follicular phase (days 17
20 of the treated cycle), heat-stressed cows showed an increase in the number of
large follicles (>/= 10 mm), and the preovulatory plasma FSH surge was
significantly higher in heat-stressed cows than in cooled cows (P < 0.01). The
effect of heat stress was also observed during the first follicular wave of the
subsequent cycle: the postovulatory plasma FSH concentration was higher (P <
0.01), but fewer medium follicles developed, and the first follicular wave
decreased at a slower rate in previously heat-stressed cows than in cooled cows
(0.40 and 0.71 follicles per day, respectively). This study shows both immediate
and delayed effects of heat stress on follicular dynamics, which were associated
with high FSH and low inhibin concentrations in plasma. These alterations may
have physiological significance that could be associated with low fertility of
cattle during the summer and autumn.
PMID- 11006150
TI - Loss of myometrial oxytocin receptors during oxytocin-induced and oxytocin
augmented labour.
AB - Oxytocin is used widely for the induction and augmentation of labour, but there
is little information about the dynamics of oxytocin receptors in human
myometrium during parturition, and the possible effect of oxytocin infusion. This
information is important because G protein-coupled receptors, such as the
oxytocin receptor, undergo desensitization after prolonged or repeated
stimulation. The concentration of myometrial oxytocin receptors and the steady
state of its mRNA were measured in patients undergoing Caesarean sections before
or during spontaneous or induced labour. The concentration of receptors before
labour was 477 (175-641) fmol mg(-1) protein (median, quartile range), and
decreased to 140 (72-206; P < 0.05) and 118 (69-75; P < 0.01) fmol mg(-1) protein
during prolonged oxytocin-augmented and oxytocin-induced labour, respectively.
The corresponding oxytocin receptor mRNA concentrations decreased by 60- and 300
fold, respectively. The decrease in receptor binding and mRNA in women receiving
oxytocin infusion indicates that homologous receptor desensitization occurs in
vivo.
PMID- 11006151
TI - A staging scheme for assessing development in vitro of organogenesis stage
embryos of the stripe-faced dunnart, Sminthopsis macroura (Marsupialia:
dasyuridae).
AB - The inaccessibility of mammalian organogenesis stage embryos has precluded their
widespread use in embryological and teratological studies. As organogenesis
occurs during the last 1.5 days of the 10. 7 days of gestation in the stripe
faced dunnart (Sminthopsis macroura), the aim of the present study was to
investigate whether day 9 and day 10 embryos and fetuses could be grown to term
in vitro. High glucose Dulbecco's modified Eagle's medium with 10% fetal calf
serum (FCS) supported embryonic growth for various periods of time, some to
within 5 h of the predicted time of parturition. A roller culture system
maintained at 35 degrees C was used to incubate organogenesis stage embryos (n =
43). Nine unincubated (control) embryos were either fixed for microscopic
analysis or frozen for microprotein determination. The results of the present
study indicate that with some optimization of the culture conditions (increasing
oxygen in the gas phase in the culture tubes, replacing FCS with rat serum), it
might be possible for organogenesis stage S. macroura embryos to be grown to
term. A scoring scheme for assessing morphological development was devised for
use as a standard in staging organogenesis stage embryos. This scheme reflects
the highly compressed schedule of developmental events that occurs mainly during
day 9 of gestation in S. macroura embryos. In comparison, during embryogenesis in
Didelphis virginiana these developmental events occur from day 8 to day 10.5 of
gestation, and birth occurs on day 13.
PMID- 11006152
TI - Insulin-like growth factor I receptor mRNA and protein expression in pig corpora
lutea.
AB - Insulin-like growth factor I (IGF-I) is believed to play a luteotrophic role in
the pig corpus luteum during the oestrous cycle. Since the actions of IGF-I in
target tissues are mediated by the type I IGF receptor, the concentrations of IGF
I receptor mRNA and protein were examined in pig corpora lutea at different
stages of the oestrous cycle. Corpora lutea were collected from normally cyclic
gilts on days 4, 7, 10, 13, 15 and 16 of the oestrous cycle (n = 4 animals per
day). Corpora lutea on days 7, 10 and 13 were dissociated with collagenase, and
large and small luteal cell sub-populations were separated by elutriation.
Northern and slot blots were used to examine mRNA, and western blots were used to
measure the concentrations of IGF-I receptor protein in the pig corpus luteum. On
northern blots, luteal IGF-I receptor mRNA was present as a single 11 kb
transcript. The slot blots showed that the steady state expression of IGF-I
receptor mRNA increased significantly (P < 0.05) from its lowest value on day 4,
to reach a maximum on days 13-16. IGF-I receptor mRNA was also expressed to a
greater extent in large compared with small luteal cells (P < 0.05). On western
blots, IGF-I receptor appeared as a 95 kDa protein band (beta-subunit) and IGF-I
receptor protein concentrations were significantly higher (P < 0.05) on days 4-10
than on days 13-16. Finally, large luteal cells appeared to contain more IGF-I
receptor protein than the small luteal cells. In conclusion, since IGF-I receptor
was detected in the pig corpus luteum, it is a likely target tissue for IGF-I,
especially during the early luteal phase. Furthermore, IGF-I receptor was
localized primarily on large luteal cells, thus it is hypothesized that IGF-I may
play a paracrine role in the pig corpus luteum.
PMID- 11006153
TI - Expression of intercellular adhesion molecule 1 (ICAM-1) on the human oviductal
epithelium and mediation of lymphoid cell adherence.
AB - The epithelium of the human oviduct expresses the major histocompatibility
complex (MHC) class II and shows endocytic properties towards luminal antigens.
Therefore, the epithelial cells might behave as antigen-presenting cells,
inducing a local immune response. The activation of antigen-specific T cells not
only requires presentation of the peptide antigen by MHC class II, but also the
presence of co-stimulatory molecules in the antigen-presenting cells. Therefore,
the expression of the intercellular adhesion molecule 1 (ICAM-1) was examined in
the epithelium of the human oviduct. Most oviducts showed epithelial ICAM-1
expression, as assessed by immunocytochemistry, western blot analysis and RT-PCR
assay, and the expression was restricted to the luminal border of ciliated and
secretory cells. Interferon gamma, interleukin 1 and lipopolysaccharide
treatments increased the percentage of ICAM-1-positive cells in primary cultures,
indicating that the expression of ICAM-1 in the oviduct might be upregulated in
vivo by inflammatory cytokines or bacterial infections. Binding assays between
allogenic phytohaemagglutinin-activated lymphocytes and epithelial monolayers
expressing ICAM-1 demonstrated that this molecule stimulated lymphocyte
adherence. The presence of ICAM-1, in addition to MHC class II, supports the
putative role of the oviductal epithelium in antigen presentation. The exclusive
apical distribution of ICAM-1 indicates that T-cell activation would occur in a
polarized manner. Binding of lymphoid cells to the surface of the oviductal
epithelium may help to retain these immune cells that are required for the
clearance of pathogens.
PMID- 11006154
TI - Expression of matrix metalloproteinases 2 and 9 in the mouse uterus during
implantation and oil-induced decidualization.
AB - During implantation, matrix metalloproteinases are believed to play roles in the
tissue remodelling that accompanies decidualization in the endometrium and in
embryo invasion. The objective of this study was to characterize further the
expression of matrix metalloproteinases 2 and 9 in the mouse uterus during early
pregnancy and oil-induced decidualization. mRNA encoding matrix metalloproteinase
2 was detected in pregnant uteri and uteri undergoing oil-induced decidualization
by northern blot analyses. The steady-state concentrations of mRNA encoding
matrix metalloproteinase 2 did not change significantly in implantation compared
with inter-implantation areas on days 5-8 of pregnancy but were significantly
lower in stimulated compared with non-stimulated uterine horns during
artificially induced decidualization. mRNA encoding matrix metalloproteinase 9
was also detected in uteri undergoing oil-induced decidualization but not in
pregnant uteri. Its concentration was significantly greater in uterine horns
undergoing oil-induced decidualization compared with control horns.
Immunoreactive matrix metalloproteinases 2 and 9 were detected in the uterus
during early pregnancy and oil-induced decidualization by immunohistochemistry,
localized to the endometrial stroma, but the staining progressively became weaker
and was absent in areas that had undergone decidualization. By day 8 of pregnancy
and 72 h after the induction of decidualization, matrix metalloproteinase 2 and 9
proteins remained mainly in the region of non-decidualized stromal cells adjacent
to the myometrium. In implantation segments, they were also localized to the
region of the trophoblast giant cells. The second objective of the present study
was to determine whether endometrial stromal cells isolated from uteri sensitized
for decidualization express matrix metalloproteinases 2 and 9. Northern blot
analyses and gelatin zymography showed that these cultured cells expressed matrix
metalloproteinase 2 and 9, and that transforming growth factor beta1
significantly increased matrix metalloproteinase 9 expression. The results of the
present study further characterize matrix metalloproteinases 2 and 9 expression
in the uterus during implantation and artificially induced decidualization.
PMID- 11006155
TI - Effects of angiotensin II on the acrosome reaction in equine spermatozoa.
AB - Angiotensin II is a hormone with a wide array of physiological effects that
exerts its effect via interaction with two major subtypes of receptor. The
results of this study show that angiotensin II (from 1 to 100 nmol l(-1))
initiates acrosomal exocytosis in equine spermatozoa that have undergone
capacitation in vitro in a TALP-TEST (Tyrode's albumin lactate pyruvate; 188.7
mmol TES l(-1), 84.8 mmol Tris l(-1)) buffer with cAMP. The acrosome reaction and
sperm viability were assessed with fluorescein isothiocyanate-Pisum sativum
agglutinin (FITC-PSA) and Hoechst 33258, respectively. The initiation of the
acrosome reaction by angiotensin II was strongly inhibited by losartan, a
specific angiotensin II type 1 receptor antagonist. Although angiotensin II as
well as progesterone both initiated the acrosome reaction in equine spermatozoa,
there was no synergistic effect when both agonists were added simultaneously.
Initiation of acrosomal exocytosis by angiotensin II was accompanied by a rapid
and transient calcium influx that was assessed in capacitated spermatozoa loaded
with Fura-2AM. In addition, the angiotensin II-mediated calcium influx was
inhibited when spermatozoa were preincubated with losartan. Western blotting with
an antibody against angiotensin II type 1 receptor detected a major sperm protein
of 60 kDa. Indirect immunofluorescence of non-capacitated spermatozoa with the
angiotensin II type 1 receptor antibody revealed labelling in the midpiece and
tail. In capacitated spermatozoa, the angiotensin II type 1 receptor was
localized mainly over the anterior region of the sperm head, the equatorial
segment and occasionally on the postacrosomal region in addition to the sperm
tail. In conclusion, this study demonstrated the ability of angiotensin II to
stimulate the acrosome reaction in capacitated equine spermatozoa. This effect is
mediated via the angiotensin II type 1 receptor and is accompanied by an increase
in intracellular calcium.
PMID- 11006156
TI - Reproductive characteristics of the african pygmy hedgehog, atelerix albiventris.
AB - To obtain further perspective on reproduction and particularly gamete function
among so-called primitive mammals presently grouped in the Order Insectivora, we
have examined the African hedgehog, Atelerix albiventris, in light of unusual
features reported in shrews and moles. Atelerix proves to share many but not all
of the characteristics seen in these other insectivores. The penis of Atelerix
has a 'snail-like' form, but lacks the surface spines common in insectivores and
a number of other mammals. Hedgehog spermatozoa display an eccentric insertion of
the tail on the sperm head, and they manifest the barbs on the perforatorium
that, in shrews, probably effect the initial binding of the sperm head to the
zona pellucida. As a possible correlate, the structural matrix of the hedgehog
acrosome comprises only two main components, as judged by immunoblotting, rather
than the complex of peptides seen in the matrix of some higher mammals. The
Fallopian tube of Atelerix is relatively simple; it displays only minor
differences in width and in the arborized epithelium between the isthmus and
ampulla, and shows no evidence of the unusual sperm crypts that characterize the
isthmus or ampulla, depending on the species, in shrews and moles. In common with
other insectivores, Atelerix appears to be an induced ovulator, as judged by the
ovulation of some 6-8 eggs by about 23 h after injection of hCG. The dense
cumulus oophorus appeared to have little matrix, in keeping with the modest
dimensions of the tubal ampulla and, while it was not quite as discrete as that
of soricids, it did show the same insensitivity to 0.5% (w/v) ovine or bovine
hyaluronidase.
PMID- 11006157
TI - Control of ovarian follicular growth and maturation by the corpus luteum and the
placenta during pregnancy in sheep.
AB - Ovarian follicular growth and maturation and its control throughout pregnancy
have not been described fully in sheep. Experiment 1 characterized the size and
maturation (steroid production in vitro and aromatase activity) of ovarian
follicles obtained at days 20, 50, 80 and 110 of pregnancy compared with those
obtained at day 12 of the oestrous cycle. There was no difference in the number
of small follicles (< 3 mm in diameter) between cyclic and pregnant ewes,
regardless of the stage of pregnancy. There was a marked reduction (P < 0.01) in
the number of medium follicles (3-5 mm) starting at day 80 of pregnancy. Large
follicles (> 5 mm) were not detected at day 110 of pregnancy. In vitro
testosterone output by follicles was constant throughout pregnancy. Oestradiol
output remained steady until day 80, but decreased markedly at day 110 of
pregnancy. This decrease was associated with a reduction in aromatase activity in
follicles obtained at this stage. Experiment 2 examined the effect of
administration of high concentrations of progesterone between day 100 and day 120
after mating on resumption of follicular growth in ewes that underwent Caesarean
section at day 99 of pregnancy. In ewes that underwent Caesarean section,
progesterone supplementation was successful in mimicking the profile found in
pregnant ewes, but did not prevent re-initiation of follicular growth, as
demonstrated by the presence of large follicles (> 5 mm) at day 120 after mating.
Experiment 3 examined the effects of PGF(2alpha)-induced regression of the corpus
luteum of day 100 of pregnancy on resumption of follicular growth. High
concentrations of PGF(2alpha) (0.28 mg kg(-1) body weight) administrated at day
100 of pregnancy were required to initiate regression of the corpus luteum. At
day 120 after mating, the mean (+/- SEM) diameter of the largest follicle in
PGF(2alpha)-treated ewes (3.40 +/- 0.47 mm) was significantly greater (P < 0.05)
than that in control pregnant ewes (2.52 +/- 0.34 mm). Experiment 4 examined the
effect of removal of the fetus and of the corpus luteum at day 100 of pregnancy
on resumption of ovulation. Removal of the corpus luteum by PGF(2alpha) treatment
at the time of removal of the fetus resulted in earlier occurrence of short
luteal phases (27.8 versus 40.6 days, PGF(2alpha)-treated versus non-treated) but
did not alter the timing of the first normal luteal phases (41 days). In
conclusion, the results from these experiments indicate that placental compounds
play a major role in inhibiting follicular growth and maturation during late
pregnancy in sheep.
PMID- 11006158
TI - Gonadotrophin secretion in prepubertal bull calves born in spring and autumn.
AB - The reproductive development of bull calves born in spring and autumn was
compared. Mean serum LH concentrations in calves born in spring increased from
week 4 to week 18 after birth and decreased by week 24. In bull calves born in
autumn, mean LH concentrations increased from week 4 to week 8 after birth and
remained steady until week 44. LH pulse amplitude was lower in bull calves born
in autumn than in calves born in spring until week 24 of age (P < 0.05). There
was a negative correlation between LH pulse frequency at week 12 after birth and
age at puberty in bull calves, irrespective of season of birth, and LH pulse
frequency at week 18 also tended to correlate negatively with age at puberty.
Mean serum FSH concentrations, age at puberty, bodyweight, scrotal circumference,
testes, prostate and vesicular gland dimensions, and ultrasonographic grey scale
(pixel units) were not significantly different between bull calves born in autumn
and spring. However, age and body-weight at puberty were more variable for bull
calves born in autumn (P < 0.05). In a second study, bull calves born in spring
received either a melatonin or sham implant immediately after birth and at weeks
6 and 11 after birth. Implants were removed at week 20. Mean LH concentrations,
LH pulse frequency and amplitude, mean FSH concentrations and age at puberty did
not differ between the two groups. No significant differences between groups in
the growth and pixel units of the reproductive tract were observed by
ultrasonography. In conclusion, although there were differences in the pattern of
LH secretion in the prepubertal period between bull calves born in autumn and
spring, the postnatal changes in gonadotrophin secretion were not disrupted by
melatonin treatment in bull calves born in spring. Reproductive tract development
did not differ between calves born in spring and autumn but age at puberty was
more variable in bull calves born in autumn. LH pulse frequency during the early
prepubertal period may be a vital factor in determining the age of bull calves at
puberty.
PMID- 11006159
TI - Effects of recent sexual experience and melatonin treatment of rams on plasma
testosterone concentration, sexual behaviour and ability to induce ovulation in
seasonally anoestrous ewes.
AB - The aim of this study was to determine whether advancing the seasonal changes
associated with rams by treatment with exogenous melatonin and allowing the rams
previous sexual experience would increase the proportion of anoestrous ewes
ovulating in early July. North Country Mule ewes (n = 225) were grouped by live
body weight and body condition score and allocated randomly to the following
treatments: (i) isolated from rams (control; n = 25); (ii) introduced to rams
(treatment 2); (iii) introduced to rams that had mated with ewes during the
previous 2 days (treatment 3); (iv) introduced to rams implanted with melatonin
(treatment 4); and (v) introduced to rams that were implanted with melatonin and
had mated with ewes during the previous 2 days (treatment 5). Treatments 2-5 were
replicated (2 x 25 ewes) and two rams were introduced to each replicate group.
Introductions began on 4 July and were completed by 11 July. The rams were
withdrawn from the ewes after 8 days. Melatonin was administered as a
subcutaneous implant (Regulin((R))) on 22 May and again on 20 June. Blood samples
were taken from all rams to determine plasma melatonin and testosterone
concentrations (19 samples in 6 h). The behaviour of the sheep was videotaped
continuously during the first 3 h after the ram was introduced. Ovulation was
detected by an increase in plasma progesterone concentrations from < 0.5 ng ml(
1) to > 0.5 ng ml(-1). Mean +/- SE plasma melatonin concentrations were 649.7 +/-
281.4 and 18.3 +/- 2.4 pg ml(-1) in rams with and without melatonin implants,
respectively (P < 0.001). Melatonin implants also increased plasma testosterone
concentrations from 4.30 +/- 1.88 to 10.10 +/- 1.10 ng ml(-1) (P < 0.01), the
libido of the rams and the proportion of ewes that ovulated in response to the
rams (43 and 56% (treatments 4 and 5) versus 24% (treatments 2 and 3)). In
conclusion, implanting rams with melatonin before introducing them to seasonally
anoestrous ewes increases the proportion of ewes that ovulate in response to
introduction of a ram, but previous sexual experience of rams appears to have
little or no effect.
PMID- 11006160
TI - Effects of bromocriptine administration during the follicular phase of the
oestrous cycle on prolactin and gonadotrophin secretion and follicular dynamics
in merino monovular ewes.
AB - Two experiments using Spanish Merino ewes were conducted to investigate whether
the secretion of prolactin during the follicular phase of the sheep oestrous
cycle was involved in the patterns of growth and regression of follicle
populations. In both experiments, oestrus was synchronized with two cloprostenol
injections which were administered 10 days apart. Concurrent with the second
injection (time 0), ewes (n = 6 per group) received one of the following
treatments every 12 h from time 0 to 72 h: group 1: vehicle injection (control);
group 2: 0.6 mg bromocriptine (0.03 mg per kg per day); and group 3: 1.2 mg
bromocriptine (0.06 mg per kg per day). In Expt 1, blood samples were collected
every 3 h from 0 to 72 h, and also every 20 min from 38 to 54 h to measure
prolactin, LH and FSH concentrations. In Expt 2, transrectal ultrasonography was
carried out every 12 h from time 0 until oestrus, and blood samples were
collected every 4 h to measure prolactin, LH and FSH concentrations. Ovulation
rates were determined by laparoscopy on day 4 after oestrus. Bromocriptine
markedly decreased prolactin secretion, but did not affect FSH concentrations,
the mean time of the LH preovulatory surge or LH concentrations in the
preovulatory surge. Both doses of bromocriptine caused a similar decrease in LH
pulse frequency before the preovulatory surge. The highest bromocriptine dose led
to a reduction (P < 0.01) in the number of 2-3 mm follicles detected in the
ovaries at each time point. However, bromocriptine did not modify the total
number or the number of newly detected 4-5 mm follicles at each time point, the
number of follicles > 5 mm or the ovulation rate. In conclusion, the effects of
bromocriptine on gonadotrophin and prolactin secretion and on the follicular
dynamics during the follicular phase of the sheep oestrous cycle indicate that
prolactin may influence the viability of gonadotrophin-responsive follicles
shortly after luteolysis.
PMID- 11006161
TI - Regulation of oxytocin receptor gene expression in sheep: tissue specificity,
multiple transcripts and mRNA editing.
AB - The increase in uterine oxytocin receptor concentrations over the late luteal
phase of the oestrous cycle in sheep is thought to play an important role in the
regulation of the duration of the cycle by facilitating the effect of oxytocin on
uterine prostaglandin release. Experiments indicated that oxytocin receptor mRNA
expression in the endometrium was high at oestrus compared with at days 2, 7 and
12 of the oestrous cycle. The amount of oxytocin receptor mRNA expression in the
pituitary gland did not show any significant differences during the oestrous
cycle. Oxytocin receptor cDNA was obtained and characterized from ovine uterine
endometrium on day 15 of the oestrous cycle, using RT-PCR techniques, to study
the mechanisms underlying the resolution of oxytocin receptor expression. The
cDNA sequence for the oxytocin receptor gene in sheep was found to be similar to
that described previously, except for a difference of seven nucleotides. These
nucleotide differences resulted in changes in four of the deduced amino acids in
the oxytocin receptor sequence. The heterogeneity of the different sized oxytocin
receptor transcripts in sheep is due, at least in part, to the alternative use of
polyadenylation sites. Northern hybridization confirmed that the oxytocin
receptor gene is expressed in ovine corpus luteum. The investigations on oxytocin
receptor gene expression indicate that the patten of oxytocin receptor gene
expression in sheep is not only tissue-specific, but also highly function
related. Evidence was obtained of mRNA editing in both the coding and the 3'
untranslated (3'UTR) regions of oxytocin receptor gene transcripts in ovine
endometrium; this was the first demonstration of this phenomenon for oxytocin
receptor mRNA. The present results indicate that the observed differences in
oxytocin receptor mRNA sequences for the different oxytocin receptor populations
in endometrium are due to mRNA editing. mRNA editing of oxytocin receptor
transcripts may be reflected in changes in the amino acid composition of the
carboxyl terminus of the receptor, which would explain the differences in the
observed responses to an oxytocin challenge.
PMID- 11006162
TI - Is the action of inhibin mediated via a unique receptor?
AB - The receptor system and the molecular mechanisms by which inhibin acts on its
target cells are poorly understood, in contrast to the situation for the
structurally related molecule, activin. On the basis of evidence that the
biological action of inhibin in a number of systems resembles that of an activin
antagonist, it has been contended that inhibin operates by competition for the
activin receptor rather than through a specific inhibin receptor. However,
mounting evidence indicates that inhibin also interacts with high affinity and
specificity with membrane-binding proteins that are likely to be the putative
inhibin receptor.
PMID- 11006163
TI - Function of steroidogenic factor 1 during development and differentiation of the
reproductive system.
AB - Intact reproductive development depends on steroids and other endocrine signals.
Although recent discoveries have elucidated important steps of sexual
differentiation, the intricate mechanisms that regulate the development of
steroid-producing tissues remain elusive. In adults, complex feedback mechanisms
determine the hypothalamic and pituitary regulation of steroid hormone
biosynthesis. Steroidogenic factor 1 (SF-1), an orphan member of the nuclear
receptor superfamily of proteins, plays a critical role in development and
differentiation of the endocrine and reproductive systems. This review provides
an overview of the function of SF-1, its mechanism of action, and a perspective
on the interaction of SF-1 with other determinants of sexual differentiation.
Whereas SF-1 is essential for the expression of numerous steroidogenic enzymes,
its presence may not correlate with steroidogenic function. Moreover, diverse co
regulators modulate the influence of SF-1 on gene transcription. The significance
of these interactions is discussed in the context of reproductive development and
function. Other orphan or ligand-dependent nuclear proteins may share similar
mechanisms.
PMID- 11006165
TI - Role of mother-young interactions in the survival of offspring in domestic
mammals.
AB - The defining characteristic of mammals is that females nurse and care for their
young; without this, the neonate has no chance to survive. Studies on wild and
domestic species show that the neonatal period is the most critical step in the
lifetime of a mammal. This review compares three well-studied species (the
rabbit, pig and sheep) that differ in their parental strategies and in the
problems that neonates have to overcome. As a general trend, mother-young
interactions vary according to the maturity of the newborn, and the size of the
litter. Neonatal survival relies to a great extent on an environment that is
ecologically appropriate for the developmental stage of the neonate, and on
optimum interactions with the mother. Adaptive maternal care supposes that the
mother provides the basic needs of the neonate: warmth (in pigs and rabbits) or
shelter, food, water and immunological protection (via colostrum) and, in some
instances, protection from predators and other conspecifics. A major risk facing
all neonates, other than the birth process itself, is inadequate colostrum intake
owing to delayed suckling or competition with siblings, which leads to
starvation, hypothermia or even crushing, as has been observed in pigs.
PMID- 11006164
TI - Roles of KIT and KIT LIGAND in ovarian function.
AB - Evidence from mouse mutants indicates that the Kit gene encoding KIT, a receptor
present on the oocyte and theca cells, and the Mgf gene encoding KIT LIGAND, the
ligand of KIT, are important regulators of oogenesis and folliculogenesis.
Recently, in vitro cultures of fetal gonads, of follicles and of oocytes have
identified specific targets for the KIT-KIT LIGAND interaction. In fetal gonads,
an anti-apoptotic effect of KIT-KIT LIGAND interactions on primordial germ cells,
oogonia and oocytes has been demonstrated. In postnatal ovaries, the initiation
of follicular growth from the primordial pool and progression beyond the primary
follicle stage appear to involve KIT-KIT LIGAND interactions. During early
folliculogenesis, KIT together with KIT LIGAND controls oocyte growth and theca
cell differentiation, and protects preantral follicles from apoptosis. Formation
of an antral cavity requires a functional KIT-KIT LIGAND system. In large antral
follicles, the KIT-KIT LIGAND interaction modulates the ability of the oocyte to
undergo cytoplasmic maturation and helps to maximize thecal androgen output.
Hence, many steps of oogenesis and folliculogenesis appear to be, at least in
part, controlled by paracrine interactions between these two proteins.
PMID- 11006166
TI - Control of the immunological environment of the uterus.
AB - The uterine immune axis holds the key to solving major problems in female
reproductive health, including infertility, many pathologies of pregnancy, and
sexually transmitted disease. The molecular determinants of tolerance and
immunity in the reproductive tract are now being identified, and the governing
principles are similar to those in other mucosal tissues. Cytokines are
implicated as pivotal regulators at important 'decision-making' points in each
phase of the induction and elicitation of a response. Indeed, the flexibility to
deal appropriately with antigens as disparate as infectious micro-organisms,
spermatozoa and the conceptus is likely to be attributable to the sophistication
of the cytokine network in driving immune deviation. A better understanding of
the factors controlling the development of immune activity in the uterus,
particularly the significance of the inductive cytokine environment in
determining the destiny of T-lymphocyte responses, will assist the rational
design of new therapeutic strategies to treat immune-based reproductive
disorders.
PMID- 11006167
TI - Growth hormone: a reproductive endocrine-paracrine regulator?
AB - Growth hormone (GH) is not classically considered as a reproductive hormone,
although a vast literature indicates that it has roles in reproductive function.
It is required for sexual differentiation and pubertal maturation and it
participates in gonadal steroidogenesis, gametogenesis and ovulation. GH is also
required for fetal nutrition and growth during pregnancy and for mammary
development and lactation. Although some of these roles reflect the action of GH
on the secretion and action of LH and FSH (Chandrashekar and Bartke, 1998), they
also reflect direct actions of GH and indirect actions mediated through the local
production of insulin-like growth factor I. Moreover, as GH is produced in
gonadal and mammary tissues, these actions may reflect local autocrine or
paracrine actions of extrapituitary GH, as well as the endocrine actions of
pituitary GH. The roles of GH in reproductive function are considered in this
review.
PMID- 11006168
TI - Advances in spermatogonial stem cell transplantation.
AB - Spermatogonial stem cell transplantation was first reported by Ralph Brinster's
laboratory in 1994. It has proven to be a technological breakthrough in the study
of both stem cells and Sertoli cell-germ cell interactions. This technique can be
used to transfer testicular stem cells successfully from one animal to another of
the same species (referred to as syngeneic transplants) and sometimes to an
animal of a different species (xenogeneic transplants). This transfer technique,
combined with developments in cryopreservation, long-term culture, and the
enrichment of stem cell populations makes more significant breakthroughs likely
in the near future. Ultimately, the application of spermatogonial stem cell
transfer will allow transplantation of cultured stem cells manipulated
genetically in vitro to give rise to functional male gametes with an altered
genotype. This achievement will have applications in basic science, human
medicine, and domestic and wild animal reproduction. Although progress toward
this goal has been swift, potentially significant barriers, such as the stable
incorporation of genetic material into stem cells and immunological responses to
the introduced germ cells, remain to be overcome. This article is a review of the
scientific advances made since the initial report of successful transplantation
in 1994.
PMID- 11006169
TI - Role of progesterone in peripheral nerve repair.
AB - Progesterone is synthesized in the peripheral nervous system in glial cells. The
functions of progesterone are indicated by the findings that it stimulates
neurite outgrowth from dorsal root ganglia sensory neurones in explant cultures,
accelerates the maturation of the regenerating axons in cryolesioned sciatic
nerve, and enhances the remyelination of regenerated nerve fibres. The formation
of myelin sheaths around axons is a sexually dimorphic process, as the sheaths
are thicker in female than in male regenerating nerves. The progesterone-induced
myelination is probably mediated by progesterone receptors, as it is impaired by
mifepristone (RU486), a progesterone antagonist. The stimulation of neurite
growth in the peripheral nervous system may be mediated by a progesterone
metabolite, 5alpha-tetrahydroprogesterone, through GABA(A) receptors.
PMID- 11006170
TI - [Recommendations for the prevention of respiratory syncytial virus infections.
Standards Committee of the Spanish Society of Neonatology. Board of Directors of
the Spanish Society of Neonatology].
AB - Premature babies < = 35 weeks gestation, with or without chronic lung disease
(CLD), should be considered high risk population for RSV infection and
rehospitalization. RSV monoclonal antibodies (palivizumab) have been found useful
in decreasing rates of RSV hospitalization in this patients. Guidelines for their
administration include: 1. Recommend their use in premature born between 29-32
weeks gestation without CLD and less than 6 months at entry of RSV station. 2.
Strongly recommend their use in premature babies < = 28 weeks gestation or
affected with CLD in treatment during last 6 months. These patients should be
prophylaxed for two RSV seasons. 3. Prophylaxis among premature babies between 32
35 weeks gestation is not recommended on routine bases. Each case has to be
individually analyzed considering risk factors.
PMID- 11006171
TI - [Recommendations for basic, advanced and neonatal cardiopulmonary resuscitation.
Post-resuscitation stabilization and transport. Spanish Group for Pediatric and
Neonatal Cardiopulmonary Resuscitation].
PMID- 11006172
TI - [Recommendations for basic, advanced and neonatal pediatric cardiopulmonary
resuscitation. Ethics and cardiopulmonary resuscitation. Spanish Group for
Pediatric and Neonatal Cardiopulmonary Resuscitation].
PMID- 11006173
TI - Publication bias in reproductive research.
AB - Publication bias is defined as any tendency on the part of investigators or
editors to fail to publish study results on the basis of the direction or
strength of the findings. This may lead to overestimation of treatment effects in
published work. Inappropriate decisions about patient management may result. We
investigated what proportion of abstracts at the European Society of Human
Reproduction and Embryology (ESHRE) annual meeting eventually reached full
publication, what was the time to publication, and which factors might have
affected publication. Among the 2691 abstracts of six ESHRE annual meetings, 151
(5.6%) reporting randomized controlled trials (RCT) were identified.
Comprehensive searches of electronic databases and handsearching of the two major
journals in the field yielded 79 full publications pertaining to these abstracts.
Kaplan-Meier analysis estimated 56% of RCT abstracts to be eventually published
in full, the median time to publication being 32.5 months. Positive outcome (i.e.
significant results) did not affect the publication rate, and neither did sample
size, the subject category, or the native language (English/non-English) of the
country of origin. Oral presentations resulted in eventual full publication
significantly more frequently (69%) than posters (42%). It is concluded that a
considerable publication deficit, but not a publication bias, exists for RCT in
reproductive research.
PMID- 11006174
TI - Clinical andrology: from evidence-base to ethics. The 'E' quintet in clinical
andrology.
AB - The management of the infertile man should be founded on consensus-based
medicine, i.e. the consensual opinion of experts considering evidence-based as
well as empirical or experience-based medicine, the effective cumulative rate of
successful deliveries, ethical and economic considerations. The apparent
contradictions between conclusions from experience-based medicine and evidence
based medicine regarding the efficacy of varicocele treatment and tamoxifen
treatment can be explained by scientific reasons. It is argued that the
suggestion not to implement these treatments is ill founded because of flawed
meta-analyses. The effective cumulative rate of successful deliveries and time to
pregnancy as observed in cohort studies should be considered the ultimate
touchstone of treatment efficacy. Based on the data of effective cumulative
delivery rate, cost per successful delivery, and the known prevalence of
aetiological diagnoses in infertile men, it is possible to estimate the number of
deliveries that can be attained thanks to an investment of, e.g. 1 million Euro.
This number is approximately 70-80 if IVF (including intracytoplasmic sperm
injection) is chosen as first line treatment, and four times higher if
conventional treatment (including intrauterine insemination) is applied. It is
concluded that the well thought out approach recommended by the World Health
Organization should generally be implemented for the management of couples in
whom infertility is (mainly) due to a male factor.
PMID- 11006175
TI - Hydrosalpinx and ART. Salpingectomy prior to IVF can be recommended to a well
defined subgroup of patients.
AB - The result of the Scandinavian multicentre study on salpingectomy prior to IVF
has promoted a discussion on whether there is a risk of unnecessary
salpingectomies being performed. We agree that physicians have to discriminate
carefully between a hydrosalpinx that should be removed and one that is suitable
for surgical repair. Tubal endoscopy is the most advanced tool for that purpose,
while transvaginal ultrasound is not appropriate in selecting patients to undergo
either salpingectomy or salpingostomy. The Scandinavian study showed that
patients with hydrosalpinges which are large enough to be visible on ultrasound
before ovarian stimulation, benefit from salpingectomy in terms of improved
fertility outcome after IVF. The result of the study does not interfere with the
management of distal tubal infertility in general, since it was concluded that
not every woman with a large hydrosalpinx should undergo salpingectomy.
Hydrosalpinges with preserved mucosa may be better treated with reconstructive
surgery as primary treatment instead of salpingectomy and IVF. The latter option
may, however, be the secondary treatment after failed conception and re-occlusion
of the tubes. Unnecessary salpingectomies should, of course, not be performed and
they may easily be avoided by appropriate evaluation of the tubal mucosa at
laparoscopy before any final decision of salpingectomy is made. We do not see a
major conflict: functional surgery to the tubes with healthy mucosa and
salpingectomy to the dilated tubes that are visible on ultrasound and have a
severely damaged mucosa.
PMID- 11006176
TI - Effect of different cyclical sequential progestins on endometrial vascularity in
postmenopausal women compared with the natural cycle: a morphometric analysis.
AB - The effect of trimegestone-based and norethisterone-based hormone replacement
therapy (HRT) regimens on the endometrial vascularity compared with that of the
endometrium of the natural cycle were evaluated using immunohistochemical
techniques. Endometrial vascular space area, diameter and number were defined in
the functionalis layer of the endometrial samples from postmenopausal women who
either completed a randomized, double blind, dose-ranging study of continuous
oral micronized oestradiol 2 mg daily with trimegestone 0.05, 0.1, 0.25 and 0.5
mg/day from day 15-28 for six treatment cycles or were given cyclical sequential
norethisterone (NET)-based HRT together with continuous 2 mg oral oestradiol
valerate for three cycles. The control samples were LH-dated endometrial
biopsies. NET-based HRT was associated with a higher number of smaller vascular
spaces compared with the trimegestone-treated endometrium or that of the natural
cycle. There was no dose-dependent effect in the four dose groups of
trimegestone. In conclusion, norethisterone may exert a different effect on
angiogenesis to that of trimegestone on endometrial vascular development.
PMID- 11006177
TI - Serum oestradiol and progesterone concentrations during prolonged coasting in 15
women at risk of ovarian hyperstimulation syndrome following ovarian stimulation
for assisted reproduction treatment.
AB - Serum oestradiol and progesterone concentrations were examined for up to 7 days
after withholding gonadotrophins whilst continuing pituitary down-regulation in
15 women at serious risk of severe ovarian hyperstimulation syndrome (OHSS)
(serum oestradiol >6000 pg/ml and >15 follicles per ovary). Serum oestradiol
concentrations rose on day 1 of coasting in all but two of the 15 women before
falling, the decrement being in the order of 40% on each day. This observation
permits a rational basis for the estimation of frequency of serum oestradiol
measurements and duration of coasting. The trends and rates of fall of serum
oestradiol do not seem to predict the occurrence of moderate and severe OHSS,
being similar in the six women who developed OHSS compared with nine women
without OHSS. The trends in progesterone concentrations were unrelated to any
aspects of the clinical outcome.
PMID- 11006178
TI - Effects of alendronate and hormone replacement therapy, alone or in combination,
on bone mass in postmenopausal women with osteoporosis: a prospective, randomized
study.
AB - The effectiveness of hormone replacement therapy (HRT) and alendronate, alone and
in combination, was evaluated in 120 postmenopausal patients with osteoporosis
with bone mineral density (BMD) measurements at least 2 SD below the mean value
for young premenopausal subjects. They had no contra-indications to HRT or
alendronate use and were randomized to three different treatment groups. Group I
was treated with micronized 17 beta-oestradiol 2 mg and norethisterone acetate 1
mg/day per os, group II received alendronate 10 mg/day per os and group III
received micronized 17 beta-oestradiol 2 mg, norethisterone acetate 1 mg/day per
os and alendronate 10 mg/day per os for 1 year. Elementary calcium 1500 mg/day
was supplied to patients in all three groups. Spinal and femoral neck BMD and
markers of bone mineral metabolism were measured on each patient before treatment
and 6 and 12 months after treatment in 95 patients. At the end of the 12th month,
significant increases in spinal and femoral neck BMD were found in all groups.
Increases in spinal BMD were significantly higher in patients treated with
alendronate and alendronate with HRT when compared with patients treated with HRT
only. No significant difference was found in femoral neck BMD changes between the
groups. Significant decreases in bone resorption and markers of bone formation
were observed in all groups. Alendronate was found to be more effective than HRT
and could have a very beneficial effect when added to the HRT regimen in patients
with postmenopausal osteoporosis. Alendronate might also be used in
postmenopausal patients with osteoporosis when HRT is contra-indicated or when
there is reluctance to use hormonal treatment.
PMID- 11006179
TI - Prospective randomized trial to evaluate the efficacy of a vaginal ring releasing
progesterone for IVF and oocyte donation.
AB - A polysyloxane vaginal ring containing 1g of natural progesterone was developed
as luteal supplementation for women treated with IVF-embryo transfer and for
agonadal women participating in an oocyte donation programme. The ring provides
continuous release of progesterone (10-20 nmol/l) for 90 days. The efficacy of
this form of progesterone supplementation was evaluated in two multicentre
prospective randomized trials. IVF-embryo transfer trial: After oocyte
aspiration, 505 women were randomly allocated to progesterone supplementation
with vaginal ring or i.m. progesterone (50 mg/day). The clinical pregnancy rate
was 36.6% in both groups. Implantation rate was 15.9% in the vaginal ring and
16.0% in i.m. progesterone. Oocyte donation trial: After endometrial
proliferation with micronized oestradiol, 153 women were allocated to
progesterone replacement with a vaginal ring or i.m. progesterone (100 mg/day).
Clinical pregnancy rate was 39.8 and 28.6% respectively. Implantation rate was
significantly higher with the vaginal ring compared with i.m. progesterone (19.9
and 11.6% respectively, P = 0.006). The vaginal ring is a novel development which
provides continuous release of progesterone for 90 days. In IVF-embryo transfer,
its effectiveness is similar to daily i.m. injections. In oocyte donation the
ring provides a progestative milieu which improves the implantation rate and
eliminates the discomfort of daily i.m. injections.
PMID- 11006180
TI - Prediction models for insulin resistance in the polycystic ovary syndrome.
AB - Women with the polycystic ovary syndrome (PCOS) have a high prevalence of insulin
resistance, with consequent increased risk of metabolic diseases later in life.
An early metabolic screening would therefore be of clinical relevance. By using
stepwise regression analysis on several variables obtained in 72 women with PCOS,
we constructed simple and reliable mathematical models predicting insulin
sensitivity, as measured by the euglycaemic hyperinsulinaemic clamp. The normal
ranges of insulin sensitivity were calculated from 81 non-hirsute, normally
menstruating women with normal ovaries, and similar body mass index (BMI) and age
as the women with PCOS. Measured variables included BMI, waist and hip
circumferences, truncal-abdominal skin folds, circulating concentrations of
gonadotrophins, androgens, sex hormone-binding globulin (SHBG), triglycerides,
total cholesterol and cholesterol subfractions, fasting insulin, C-peptide and
free fatty acids. The three best prediction models included waist circumference,
together with insulin (model I: R(2) = 0.77), serum triglycerides (model II: R(2)
= 0.65), and the subscapularis skin fold (model III: R(2) = 0. 64). Using
reference limits for insulin sensitivity obtained in the 81 normal pre-menopausal
women, the models identify insulin resistant women with PCOS. These simple and
inexpensive models are potentially useful in clinical practice as an early
screening in women with PCOS.
PMID- 11006181
TI - Reproductive hormones, cancers, and conditions in relation to a common genetic
variant of luteinizing hormone.
AB - A variant of the beta-subunit of luteinizing hormone (v-LH) is more common among
populations also at higher risk for breast and ovarian cancer. To explore the
possible relationship between these cancers and v-LH, we examined its frequency
in premenopausal women, including 100 with a family history of ovarian cancer, 94
with carcinoma- in-situ of the breast, and 153 age and residence-matched
controls. Reproductive histories were assessed and v-LH status measured by
immunological assays from plasma drawn during the early follicular phase of
cycles. For the entire study population, 283 (81.5%) were wild type; 61 (17.6%)
were heterozygous; and three (0.9%) were homozygous for v-LH. Carrier frequency
was not elevated among women with a family history of ovarian cancer or personal
history of carcinoma-in-situ of the breast compared with controls. Women with the
v-LH variant were less likely to report menstrual weight gain or ovarian cysts,
more likely to report infertility, and have higher early follicular phase LH
concentrations compared with women who were wild type. While there is no evidence
from this study that v-LH increases risk for ovarian or breast cancer, we
conclude that possession of v-LH may impact on some aspects of reproductive
history and LH concentrations.
PMID- 11006182
TI - Why are boys more likely to be preterm than girls? Plus other related conundrums
in human reproduction.
AB - The present note offers two quite different points of interest. The first
concerns the cause(s) of preterm labour. This is an important practical problem
because of the associated morbidity and mortality. The second point of interest
is theoretical. Some logically inter-related empirical propositions are
formulated: none has been established but evidence for each is apparently
evidence for all. However, as far as I know, there is no formal method of
treating such material. It would be useful if methodologists would offer an
opinion on whether the practical problem of the causes of preterm birth could be
helpfully approached by the accumulation of data on the propositions outlined
here. In my opinion, critics should not assess these propositions piecemeal, but
should consider the whole edifice of propositions simultaneously. Obstetricians
who confine their attention to the delivery of babies should extend it to the
circumstances surrounding the conception of those babies. For there may lie the
solution to the problem of why boys are more likely to be preterm than girls.
PMID- 11006183
TI - Hysteroscopic appearance of the mid-secretory endometrium: relationship to early
phase pregnancy outcome after implantation.
AB - A total of 172 patients who underwent hysteroscopic assessment of the endometrium
and then became pregnant, was analysed retrospectively to explore the
relationship between endoscopic findings and early phase pregnancy outcome after
implantation. Histological examination of the endometrium and assay of serum
progesterone and oestrogen were carried out simultaneously with hysteroscopy. Of
172 patients, 12 were excluded. Of the remaining 160 patients, 62 (38.8%) were
classified endoscopically as having 'good' mid-secretory endometrium and 98
(61.3%) as 'poor', between one and four cycles prior to the conception cycle.
There were no clinical differences between these two groups, except that the
frequency of patients with a history of early abortion was significantly higher
in the 'poor' group (25.5%) than in the 'good' group (8.1%) (P < 0.05). Of 160
pregnancies, 118 persisted successfully to live birth, but 42 ended in early
pregnancy loss. The incidence of early abortion was significantly higher in the
'poor' group (33.7%) than in the 'good' group (14.5%) (P < 0.05). Significant
differences were observed between the two groups for histological dating of the
endometrium (P < 0.05) but not for serum progesterone and oestradiol
concentrations or progesterone:oestradiol ratio. In conclusion, our data suggest
that the hysteroscopic appearance of the mid-secretory endometrium at this stage
of the menstrual cycle is a better prognostic factor for pregnancy outcome than
hormonal data.
PMID- 11006184
TI - Different patterns of structural luteolysis in the human corpus luteum of
menstruation.
AB - Structural luteolysis is a complex process responsible for the elimination of the
corpus luteum (CL). The aim of this study was to analyse the luteolytic process
of the CL of menstruation. For this, we have morphologically studied 654 ovaries
from 340 cycling women. Apoptotic cells were observed almost exclusively during
the perimenstrual period and were extremely scarce at advanced stages of
involution. Steroidogenic luteal cells surviving to the perimenstrual apoptotic
wave underwent characteristic degenerative changes, consisting of intense
cytoplasmic vacuolation, expression of macrophage markers and accumulation of
lipofuscin pigment, and they persisted for long periods of time. Accumulation of
corpora albicantia (CA) was observed in only 25% of a subset of 168 women,
whereas 28% showed involuting CL without hyalinization, consisting of clusters of
pigment-filled cells, and 46.4% showed ovaries with a mixture of CA and
involuting CL without hyalinization or involuting CL with intermediate features.
Evolution of the CL towards CA seemed to be related to the presence of a large,
blood-filled cavity. The data from this study suggested that different patterns
of structural luteolysis exist during CL involution, and that the final fate of
the involuting CL is dependent on the presence of a large, central, blood-filled
cavity.
PMID- 11006185
TI - Dehydroepiandrosterone supplementation augments ovarian stimulation in poor
responders: a case series.
AB - In patients with poor response to ovarian stimulation with gonadotrophins, growth
hormone (GH) is sometimes used to increase paracrine insulin-like growth factor-1
(IGF-1) effect. We postulated that dehydroepiandrosterone (DHEA) administration
to poor responders would augment gonado-trophin effect via a similar mechanism.
Baseline ovarian stimulation response to a cycle with DHEA in five healthy non
smoking women <41 years old was compared with day 3 FSH <20 mIU/ml. All had
documented poor response to vigorous gonadotrophin administration. After day 2
ultrasounds, DHEA-sulphate (DHEA-S), FSH, human chorionic gonadotrophin (HCG),
and testosterone were measured, and the women were given 80 mg/day of oral
micronized DHEA for 2 months. While still on DHEA, they underwent ovarian
stimulation with FSH given i.m. twice a day, and HCG (10 000 IU) at follicular
maturity, followed by intrauterine insemination. Cycle parameters assessed were
peak oestradiol, and peak oestradiol/ampoule. The DHEA/ovarian stimulation cycles
occurred between 4 and 24 months after the control cycles. After 2 months DHEA
treatment, DHEA-S increased to 544 +/- 55 microg/dl, and testosterone increased
to 67.3 +/- 6.1 ng/dl. All five subjects (six cycles; one subject had two DHEA
cycles) had increased responsiveness; peak oestradiol concentrations increased
from 266.3 +/- 69.4 pg/ml to 939.8 +/- 418.9 pg/ml. The oestradiol/ampoule ratio
increased in all six cycles, by a mean of 2.94 +/- 0.50 fold (P = 0.012). One of
the cycles resulted in a delivered twin pregnancy. In this small series, DHEA
improved response to ovarian stimulation even after controlling for gonadotrophin
dose. Supplemental DHEA treatment during ovarian stimulation may represent a
novel way to maximize ovarian response.
PMID- 11006186
TI - Oocyte and semen donation: a survey of UK licensed centres.
AB - In view of the difficulties encountered by licensed clinics in the recruitment of
oocyte and semen donors, the present survey was commissioned by the National
Gamete Donation Trust (NGDT) to provide systematic information on current
practice as a basis for planning future recruitment strategies. Sixty-four
clinics agreed to participate in the survey, of which 55 recruited oocyte donors,
30 recruited semen donors, and 24 recruited both oocyte and semen donors. Almost
all of the clinics had experienced difficulty in obtaining a sufficient supply of
donated oocytes, and many patients requiring treatment with donated oocytes were
placed on a waiting list for more than one year. Three-quarters of potential
donors changed their mind about donating after receiving information on the
procedures involved. The difficulties in recruiting semen donors were generally
less acute. In this case, the greatest problem was the high proportion of
potential semen donors who were deemed unsuitable after completing the screening
process. Clinics also reported a shortage of both oocyte and semen donors from
specific ethnic groups.
PMID- 11006187
TI - The outcome of IVF-embryo transfer treatment in patients who develop three
follicles or less.
AB - Among 828 patients undergoing IVF-embryo transfer treatment, the implantation and
pregnancy rates of patients who developed < or = 3 follicles were compared
prospectively with those patients who had a normal response. Patients who
developed 1 to 3 follicles during ovarian stimulation elected to proceed with
oocyte collection, have intrauterine insemination if appropriate, or to have
their cycle cancelled. In the group of patients who developed < or = 3 follicles
and who were aged <40 years, despite a significantly lower number of oocytes
collected [2 versus 7; median difference (MD) = 9; confidence interval (CI) = 7
11, and lower number of embryos developed and transferred (1 versus 3; MD = 2; CI
= 1-2), no difference in either implantation rate [27.8 versus 20.4%; odds ratio
(OR) = 1.58; CI = 0.46-4.54] or pregnancy rate (27.8 versus 36.7%; OR = 0.7; CI =
0.2-2.0) was noted when compared with similarly aged patients who developed >3
follicles. However, in patients aged >40 years who developed < or = 3 follicles,
a moderate, albeit non-significant decrease in implantation rate (3.8 versus
7.8%; OR = 1.91; CI = 0.4-57.0) and pregnancy rate (4.2 versus 18.3%; OR = 1.92;
CI = 0.38-57.0) was observed when compared with patients of a similar age who
developed >3 follicles. Patients aged <40 years, unlike older patients, maintain
good implantation and pregnancy rates despite a poor response to ovarian
stimulation. This study indicates that for this group of women, continuation of
IVF treatment is a better option than cancellation.
PMID- 11006188
TI - Addition of GnRH antagonist in cycles of poor responders undergoing IVF.
AB - Concern about the use of gonadotrophin-releasing hormone (GnRH) agonists in
ovarian stimulation of poor responder IVF patients has arisen from the claim that
GnRH agonists might have a direct deleterious effect through their receptors on
the ovary. In this study, we compared two ovarian stimulation protocols in which
no GnRH agonists were used. In all, 40 patients with a poor response in previous
treatment cycles were included. They were divided into two groups: group I (n =
20) received ovarian stimulation for 20 cycles, without the addition of either
GnRH agonist or antagonist; while group II (n = 20) patients received ovarian
stimulation for 20 cycles, including the administration of a GnRH antagonist
(Cetrorelix, 0.25 mg daily) during the late follicular phase. There was no
statistically significant difference between the groups for mean age, duration of
infertility, baseline FSH concentration, cancellation rate, number of ampoules of
gonadotrophin used, number of mature oocytes retrieved, oestradiol concentrations
on the day of injection of human chorionic gonadotrophin (HCG), fertilization
rate and number of embryos transferred. The clinical pregnancy and implantation
rates in group II appeared higher than in group I, but were not significantly
different (20 and 13.33% compared with 6.25 and 3.44% respectively). The addition
of GnRH antagonists to ovarian stimulation protocols might be a new hope for poor
responder IVF patients, but this report is preliminary and further controlled
randomized prospective studies with larger sample sizes are required.
PMID- 11006189
TI - Comparison of two different doses of lignocaine used in paracervical block during
oocyte collection in an IVF programme.
AB - We have recently demonstrated the efficacy of paracervical block (PCB) used in
conjunction with conscious sedation during egg collection. The dosage of
lignocaine used in various studies ranges from 50 mg to 200 mg. There are,
however, no studies evaluating the efficacy of different doses of local
anaesthetic agents used in PCB. In this prospective, double-blind and placebo
controlled study, 150 women undergoing egg collection in their first IVF cycle
were randomized to receive 200 mg and 150 mg lignocaine in PCB. No differences
were seen in the demographic data, the ovarian responses, the duration of egg
collection and the number of follicles punctured. The fertilization, implantation
and pregnancy rates were similar when either 150 mg or 200 mg lignocaine was
employed. The median pain levels during vaginal punctures were 14.0 (2.5th-97.5th
centiles: 0-75.4) and 14.0 (2.5th-97.5th centiles: 0-86.5) in patients receiving
200 mg and 150 mg lignocaine respectively, whereas the corresponding median
abdominal pain levels were 14.0 (2.5th-97.5th centiles: 0-85.6) and 14.0 (2.5th
97.5th centiles: 0-99.1). These pain levels during egg collection were not
significantly different between the two groups. The use of 200 mg lignocaine in
PCB is not justified, even in the absence of toxic effects.
PMID- 11006190
TI - Successful pregnancy and birth after IVF in a woman with cystic fibrosis.
AB - As survival increases, patients with cystic fibrosis (CF) are often confronted
with reproductive issues. Initial reports gave conflicting advice regarding the
outcome of pregnancy in CF. However a recent large longitudinal study of
pregnancies in CF women suggested that pregnancy has little impact on morbidity
or mortality. Reduced fertility in CF women has been described, possibly due to
thickened cervical mucus, and intrauterine insemination (IUI) has been used to
overcome this. We report the first woman with CF, to our knowledge, to be
successfully treated with IVF after repeated failed attempts at IUI.
PMID- 11006191
TI - Fertility preservation of boys undergoing anti-cancer therapy: a review of the
existing situation and prospects for the future.
AB - With the advancement of medical science, most cancers in children are now
treatable, the cure rate being almost 85%. In boys, one side effect of treatment
(chemotherapy and radiotherapy) is destruction of the sperm precursor cells in
the testis, resulting in the failure of sperm formation after puberty, and
consequent infertility. At the time of anti-cancer treatment, future fertility of
the boy patient is at the very bottom of the relative quality of life (RQL)
parameters list; however, in adults infertility is an important issue following
cure from cancer. In this article we have first reviewed the existing situation
with regard to the state of the art of fertility preservation in young boys with
cancer, and have then raised clinical and ethical issues and suggested a way
forward. The review concludes with the emphasis that certain important issues
still need to be resolved and, until these are, then the different techniques
available should be confined to approved, ethical clinical trials where efficacy
and safety can be fully evaluated.
PMID- 11006192
TI - Membrane fluidity predicts the outcome of cryopreservation of human spermatozoa.
AB - Semen cryopreservation is an important procedure in the treatment of human
infertility. However, the ability of spermatozoa to survive freeze/thaw processes
varies between patients. Cryopreservation-induced stress may result in membrane
injury with consequent loss of sperm motility and viability. We investigated the
relationship between the physico-chemical state of the human sperm membranes and
their tolerance to cryopreservation. Conventional characteristics of 20 semen
samples were analysed before and after cryopreservation as well as their membrane
fluidity assessed by measuring the fluorescence polarization anisotropy, which is
inversely proportional to the fluidity. Correlation between fluidity and post
thaw recoveries of motile and viable spermatozoa were examined. Results showed
that membrane anisotropy markedly varies between patients. In cryopreserved
spermatozoa, anisotropy values were significantly higher than in fresh
spermatozoa. Furthermore, recovery of motile and viable spermatozoa after
freeze/thaw was strongly correlated with anisotropy of fresh spermatozoa (P <
0.05). The higher the membrane fluidity was before freezing, the better was the
response of spermatozoa to cryopreservation. The results indicate that the
freeze/thaw process results in a rigidifying effect on the sperm membrane and
suggest that sperm adaptability to freeze/thaw-induced stress could be dependent
on their initial membrane fluidity. The latter finding has practical implications
for predicting the response of spermatozoa following freezing and thawing and for
improving the recovery of viable spermatozoa.
PMID- 11006193
TI - Frequency of hyper-, hypohaploidy and diploidy in ejaculate, epididymal and
testicular germ cells of infertile patients.
AB - The hypothesis that sperm aneuploidy and diploidy increase as a function of
spermatogenesis impairment was addressed. Ejaculated semen samples from a series
of men (n = 22) with very low total normal motile count (1 x 10(6)) was analysed
in terms of sperm aneuploidy and diploidy by in-situ hybridization and compared
with controls (n = 10). Germ cell aneuploidy was also analysed in an additional
series of infertile patients presenting unexplained infertility (n = 3),
congenital absence of the vas deferens (CAVD) (n = 6) and non-obstructive
azoospermia (n = 3) undergoing IVF, microsurgical epididymal sperm aspiration
(MESA)/ICSI and testicular sperm extraction (TESE)/ICSI cycles respectively. In
situ hybridization for chromosomes 1, 17, X and Y was performed on ejaculate,
epididymal and testicular spermatozoa. Significantly higher sperm aneuploidy and
diploidy rates where found (for the four chromosomes analysed) in spermatozoa
from oligoasthenoteratozoospermia (OAT) over controls (18 versus 2.28% and 2.8
versus 0.13% respectively; P < 0.001). Testicular germ cells had even higher
rates of sperm aneuploidy and diploidy. However, in this group it was difficult
to determine whether the cells analysed were dysmorphic spermatozoa or
spermatids. The data warrant further investigation on the cytogenetic
abnormalities found in most germ cells identified in testicular tissue biopsies
of azoospermic patients.
PMID- 11006194
TI - Improvement in motion characteristics and acrosome status in cryopreserved human
spermatozoa by swim-up processing before freezing.
AB - The purpose of this study was to examine if selecting a sperm population with
improved motion characteristics before freezing reduces the deleterious effects
of cryopreservation. Semen specimens from 15 normal donors were divided into two
equal aliquots. The first aliquot received no treatment (control), and the second
was processed by swim-up from a washed sperm preparation to select a sperm
population with better motility and motion characteristics (swim-up). Both
aliquots were cryopreserved by the liquid nitrogen vapour method. Percentage
motility and motion characteristics were evaluated by computer-assisted semen
analysis. Acrosome integrity as well as spontaneous and calcium ionophore-induced
acrosome reactions before freezing and after thawing were assessed by fluorescein
isothiocyanate conjugated peanut agglutinin combined with a supra vital dye
(Hoechst-33258). Swim-up processing enabled selection of a sperm population with
better motion characteristics, percentage motility and viability before freezing
(P < 0.001), but with no difference in percentage of acrosome-intact spermatozoa
(P = 0.63). After thawing, the swim-up specimens exhibited faster velocity and
progression than untreated specimens (P < 0.001). They also had higher
percentages of spermatozoa with intact acrosomes and spermatozoa able to undergo
acrosome reaction in response to calcium ionophore (P < 0.05). Selecting a highly
motile sperm population before freezing enhances overall post-thaw spermatozoa
quality.
PMID- 11006195
TI - Differential expression and localization of de-novo synthesized endometriotic
haptoglobin in endometrium and endometriotic lesions.
AB - Endometriosis protein-I (ENDO-I) mRNA expression and protein localization were
evaluated using in-situ hybridization and immunohistochemistry in endometriotic
lesions and eutopic endometrium from women with endometriosis, and in eutopic
endometrium from women without endometriosis (controls). When present, ENDO-I
mRNA and protein were observed in the functionalis zone of endometrial stroma and
the stroma of endometriotic lesions. Expression and localization differences were
scored and statistically analysed. During the secretory stage, ENDO-I mRNA
expression by endometriotic lesions and eutopic endometrium from women with
disease was significantly greater than ENDO-I mRNA expression by proliferative
stage eutopic endometrium from women with disease or eutopic endometrium from
controls, regardless of cycle stage (P < 0.001). More ENDO-I protein was
localized in endometriotic lesions and eutopic endometrium from women with
disease than in eutopic endometrium from controls, regardless of cycle stage (P <
0.001). Differential expression and localization of ENDO-I may help develop
minimally invasive diagnostic strategies for endometriosis. Further, as ENDO-I
shares nucleotide sequence and amino acid sequence with hepatic haptoglobin-which
in certain disease states is immunosuppressive and angiogenic-differences in ENDO
I expression and localization in the peritoneal cavity may contribute to the
pathogenesis of endometriosis and/or facilitate development of unprecedented
diagnostic or therapeutic approaches for management of this enigmatic disease.
PMID- 11006196
TI - Safety of cryopreservation straws for human gametes or embryos: a preliminary
study with human immunodeficiency virus-1.
AB - The aim of this preliminary experimental study was to test the stability of
cryopreservation straws to human immunodeficiency virus-1 (HIV-1). Three kinds of
straws were tested: four polyvinyl chloride (PVC), four polyethylene
terephthalate glycol (PETG) and 20 high-security ionomeric resin (IR). The PVC
and PETG straws were sealed ultrasonically, and the IR straw by thermosoldering.
Each sealed straw was cut in half to produce two demi-straws and then filled with
100 microl of HIV-1-containing supernatant (reverse transcriptase activity: 15
000 c.p.m./50 microl). The unsealed cotton end of PVC and PETG straws and the two
halves of the IR straws (cotton and plastic plug ends) were tested. Each demi
straw was two- thirds submerged in RPMI medium at 37 degrees C, and RPMI samples
were withdrawn on days 3, 7 and 11. Viral RNA was extracted from the medium and
then amplified by reverse transcriptase-polymerase chain reaction (RT-PCR)
followed by nested PCR using primers specific to HIV-1 protease. On day 7, no HIV
1 RNA was detected in any of the different samples of medium that had surrounded
the unsealed PVC and PETG straws with cotton ends, but three IR specimens were
positive. On day 11, PVC and PETG remained negative but HIV-1 RNA was detected in
RPMI samples for two more IR demi-straws (n = 5). In conclusion, under these
experimental conditions (at 37 degrees C), the unsealed cotton end PVC, PETG and
thermosoldered cotton end IR demi-straws appeared to be safe for HIV-1, while IR
straws, sealed or unsealed with a plastic plug and with unsealed cotton ends,
leaked.
PMID- 11006197
TI - Morphological evaluation of human embryos and derivation of an embryo quality
scoring system specific for day 3 embryos: a preliminary study.
AB - A scoring system specific for day 3 embryos has not been extensively explored.
Most IVF laboratories continue to grade embryos solely on the basis of cell
number and percentage fragmentation as was traditionally done for day 2 embryos.
Additional morphological features, some unique to day 3 embryos, may be useful in
selecting embryos most likely to blastulate and implant. The objective of this
study was to derive an embryo scoring system for day 3 transfers which is
predictive of positive pregnancy outcomes. A total of 316 transferred embryos
from 93 patients was recorded on videotape and evaluated. The following
parameters were used to grade the embryos: cell number, fragmentation pattern
(FP), cytoplasmic pitting, compaction, equal sized blastomeres, blastomere
expansion and absence of vacuoles. The clinical pregnancy rate was 41.9%, with an
implantation rate of 18% per embryo transferred. The mean number of embryos
transferred per patient was 3.4. Three formulae were derived to score embryo
quality in each transfer based on the average score of individual embryos
transferred. In the first scoring system, cell number alone was used to predict
pregnancy outcome. The second scoring system was based on blastomere number and
the observed FP. The third scoring system utilized both blastomere number and FP
but also combined this with five morphological criteria to yield a final day 3
embryo quality (D3EQ) score. We found the D3EQ score to be prognostic of
pregnancy outcome. This study suggests that although cell number and FP are
certainly predictors of positive pregnancy outcomes, additional parameters
specific to day 3 embryos should be used to stratify a cohort of embryos further.
PMID- 11006198
TI - The effect of propofol anaesthesia on oocyte fertilization and early embryo
quality.
AB - Propofol, frequently used for i.v. induction of anaesthesia in assisted
reproduction procedures, has been suspected of damaging oocytes. Concentrations
of propofol have recently been shown to increase in follicular fluid during
oocyte retrieval. Our study was designed to assess whether exposure to increasing
concentrations of propofol has a measurable effect on in-vitro fertilization,
cleavage and embryo development. A cohort of 130 women underwent i.v. anaesthesia
using propofol and fentanyl. Time of anaesthesia from i. v. injection of propofol
was measured, as were the doses of the two drugs. In 32 women expected to have
more than 15 oocytes retrieved, first, middle and last oocytes were cultured
separately. The mean time from i.v. injection to first follicle aspiration was
200 s. The mean time for the aspiration of each additional oocyte was 17.6 s. In
10 out of 11 cases where follicular fluid concentrations of propofol were
measured, there was an increase from the first to the last follicle, but no
difference was found in the ratio of mature to immature oocytes. Nor were any
differences found in fertilization, cleavage and embryo cell number. In so far as
in-vitro development reflects embryo quality, we conclude that the time elapsed
between retrieval of the first and last oocyte does not affect oocyte quality.
PMID- 11006199
TI - The use of whole rat embryo culture as a technique for investigating potential
serum toxicity in recurrent miscarriage patients.
AB - Previously, the rat embryo model has been used as an experimental technique in
investigations of the aetiology of idiopathic recurrent miscarriage. The aim of
the present study was to validate it as a tool in the investigation of the
aetiology of this condition. Subjects (n = 36) with a history of recurrent
miscarriage were recruited from two dedicated recurrent miscarriage clinics and
compared with control women with at least one previous pregnancy resulting in a
live birth (n = 23). Serum from each woman was used as culture medium in the rat
embryo model. Cultured embryos were scored for growth and differentiation. No
statistical difference was found in any parameter between the two groups.
Furthermore, patients from the recurrent miscarriage group whose serum
demonstrated a trend towards lower scores, subsequently conceived and underwent
uncomplicated pregnancies.
PMID- 11006200
TI - Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg
every 3 h) misoprostol when combined with mifepristone in termination of second
trimester pregnancy.
AB - It is known that when misoprostol is given at 200 microg every 3 h after
mifepristone pretreatment, the vaginal route is more effective than the oral
route. However, women prefer the oral route. This randomized study was to test
our hypothesis that oral misoprostol 400 microg is as effective as vaginal
misoprostol 200 microg when given every 3 h in termination of second trimester
pregnancy after priming with mifepristone. A total of 142 patients was randomly
assigned to group 1 (200 mg mifepristone + 400 microg oral misoprostol every 3 h
up to five doses) or group 2 (200 mg mifepristone + 200 microg vaginal
misoprostol every 3 h up to five doses). The incidence of side-effects and the
preference study were assessed through a standardized questionnaire during and
after the abortion. For the oral group, both the incidence of diarrhoea (40.0
versus 23.2%, P = 0.03) and the amount of drug used (1734 compared with 812
microg, P < 0.0001) were significantly higher than that of the vaginal group but
the incidence of fever appeared to be lower (not significant). There was no
significant difference in complete abortion rate: 81.4% in the oral group and
75.4% in the vaginal group. The median induction-abortion interval was similar in
the two groups (10.4 versus 10.0 h). The percentage of women who aborted in 24 h
was also similar: 57/70 (81.4%) in the oral group and 58/69 (87.0%) in the
vaginal group. Overall, 82.0% of women preferred the oral route. Oral misoprostol
(400 microg) given every 3 h up to five doses, when combined with mifepristone,
was as effective as the vaginal (200 microg) route in second trimester
termination of pregnancy. This regimen could also be offered to those women who
found repeated vaginal administration unacceptable.
PMID- 11006201
TI - Choriocarcinoma-like human chorionic gonadotrophin (HCG) and HCG bioactivity
during the first trimester of pregnancy.
AB - The objective of this study was to evaluate the distribution of choriocarcinoma
like human chorionic gonadotrophin (HCG) isoforms during first trimester
pregnancy and their relationship with in-vitro HCG bioactivity. This was done by
means of a retrospective analysis of patients' sera with first trimester normal
intrauterine and abnormal (ectopic) pregnancies. Serum samples were obtained from
38 women with an amenorrhoea of <10 weeks. From these, 19 had a normal
intrauterine pregnancy (IUP) and 19 an ectopic pregnancy (EP). Total
immunoreactive HCG (HCGi), free beta-HCGi and oestradiol were measured by enzyme
immunoassays and bioactive HCG by the mouse Leydig cell bioassay. The alterations
in HCG isoform content were measured by the combination of two immunometric
assays, B152 for choriocarcinoma-like HCG and B109 for intact HCG detection and
expressed as the B152/B109 ratio. Choriocarcinoma-like HCG isoforms ratio
measured by B152 and B109 assays was significantly higher in the low subgroups of
free beta-HCGi and gestational age (P = 0.0111 and 0.0036 respectively). Whereas
bioactive to immunoreactive HCG ratios (b/i ratio) were significantly higher when
free beta-HCGi concentrations were low (P = 0.0010), no correlation was found
between the variation of bioactivity (b/i ratio) and the proportion of
choriocarcinoma-like HCG isoforms (B159/B108). It is concluded that in first
trimester pregnancies (i) the modulation of HCG in-vitro bioactivity is not
related to the variation of choriocarcinoma-like HCG isoforms secretion and (ii)
the amount of choriocarcinoma-like HCG isoforms secreted by the early trophoblast
is predominant and may be the result of an early developmental regulation of
glycosylation enzyme.
PMID- 11006202
TI - A longitudinal study of maternal plasma insulin-like growth factor binding
protein-1 concentrations during normal pregnancy and pregnancies complicated by
pre-eclampsia.
AB - Insulin-like growth factor binding protein-1 (IGFBP-1) is synthesized by the
decidual stroma, and is thought to act locally to inhibit IGF activity and so
limit trophoblast invasion. Cross-sectional studies have reported conflicting
data on maternal circulating concentrations of IGFBP-1 in early pregnancy before
the development of pre-eclampsia. A longitudinal study was performed in 10 women
who went on to develop pre-eclampsia and a group of 12 normal pregnant controls,
chosen to be similar for maternal age, booking body mass index (BMI) and
gestational age. Maternal IGFBP-1 concentrations were measured in plasma obtained
at 16, 20, 24, 28, 32 and 36 weeks. Plasma IGFBP-1 concentrations were unchanged
over this period in normal pregnancy. In contrast, the concentrations in women
who developed pre-eclampsia increased progressively. At 16, 20, and 24 weeks the
concentrations were significantly lower compared to normal pregnancy, at 28 and
32 weeks, similar, but by 36 weeks the concentrations were significantly greater
than the normal controls. The data show that circulating IGFBP-1 concentrations
are lower in early pregnancy before the development of pre-eclampsia. Thus, it is
suggested that IGFBP-1-induced inhibition of IGF activity is unlikely to be
responsible for the impaired trophoblast invasion observed in pre-eclampsia.
PMID- 11006203
TI - Recurrent miscarriage--an aspirin a day?
AB - Recurrent miscarriage and later pregnancy complications are in some cases
associated with placental thrombosis and infarction. The aim of this study was to
assess the value of low dose aspirin (75 mg daily) in improving the subsequent
livebirth rate amongst women with either unexplained recurrent early miscarriage
(<13 weeks gestation; n = 805) or unexplained late pregnancy loss (n = 250).
Amongst women with recurrent early miscarriages, there was no significant
difference in the livebirth rate between those who took aspirin (251/367; 68.4%)
compared with those who did not take aspirin [278/438; 63.5%; odds ratio (OR)
1.24; 95% confidence interval (CI) 0.93-1.67]. This relationship was independent
of the number of previous early miscarriages. In contrast, women with a previous
late miscarriage who took aspirin had a significantly higher livebirth rate
(122/189; 64.6%) compared with those who did not take aspirin (30/61; 49.2%: OR
1.88; 95% CI 1.04-3.37). The empirical use of low dose aspirin amongst women with
unexplained recurrent early miscarriage is not justified. We are currently
investigating the role of incremental doses of aspirin in the treatment of women
both with early miscarriages associated with thrombophilic abnormalities and in
those with late pregnancy losses.
PMID- 11006204
TI - Chemical ripening of the cervix with intracervical application of sodium
nitroprusside: a randomized controlled trial.
AB - Nitric oxide (NO) has been found to be involved in the processes of cervical
ripening. In a randomized, placebo-controlled study, cervical softening by an
intracervical application of sodium nitroprusside, one of the most clinically
potent and effective NO donor agents, was evaluated. A total of 36 primigravid
women undergoing pregnancy termination between 9 and 12.5 weeks were enrolled. In
one series, 18 patients were randomized to receive intracervically either placebo
or 1% nitroprusside gel (5 mg), followed by uterine evacuation 6 h after
treatment. In another series, 18 patients received either placebo or 2%
nitroprusside gel (10 mg) into the cervical canal followed by uterine evacuation
3 h later. The cervical resistance, i.e. the force required to dilate the cervix
from 3 to 10 mm, was the main outcome variable. It was recorded using a force
sensing apparatus (dynamometer). Blood pressure was measured. Adverse events were
recorded until 2 h after surgery. Women treated with both doses of nitroprusside
gel showed values of cervical resistance significantly lower than those treated
with placebo gel, at any tested diameter. No differences were found between
subjects treated with the two different doses of nitroprusside. No significant
consistent changes in blood pressure were induced by either dose of
nitroprusside. No headaches were found in subjects treated with the NO donor.
This study demonstrates that sodium nitroprusside applied into the cervical canal
induces a rapid and significant softening of the cervix, thus reducing the force
required to dilate it, compared with placebo-treated subjects. The chemical
ripening of the cervix with sodium nitroprusside intracervical gel is an
efficacious procedure in first-trimester pregnancy.
PMID- 11006205
TI - Embryo reduction of multifetal pregnancies following assisted reproduction
treatment: a modification of the transvaginal ultrasound-guided technique.
AB - First-trimester transvaginal embryo reduction is an effective alternative for the
management of multifetal pregnancy in assisted reproduction. We have modified the
transvaginal technique by performing an intracardiac embryo puncture until
asystolia is verified, without the injection of any substances. Any aspiration of
embryo tissues or amniotic fluid was avoided. A total of 149 multifetal
pregnancies was reduced to twins (n = 134) or singletons (n = 15) at early
gestational age (7.8 +/- 0.8 weeks). Eleven cases (7.3%) of miscarriage, two
cases (1.3%) of chorioamnionitis, and 17 cases (11.4%) of transient spotting were
recorded as postoperative complications. Vanishing of one embryo occurred in four
cases (3.0%) of those reduced to twins. The baby take-home rate was 89.5% for
twins and 80.0% for singletons. Pregnancy outcome was analysed and compared with
a control group of women with non-reduced multiple pregnancies. The birth weight
of singleton pregnancies after reduction was lower (2929 +/- 160 versus 3291 +/-
422 g; P < 0.02). These studies show that early transvaginal intracardiac embryo
puncture is an effective and safe technique.
PMID- 11006206
TI - Chorioamnionitis decreased incidence of respiratory distress syndrome by
elevating fetal interleukin-6 serum concentration.
AB - Respiratory distress syndrome (RDS) of newborns is one of the most important
factors determining neonatal morbidity and mortality. The interleukin-6 (IL-6)
titre in cord sera of RDS-free neonates born to mothers with histological
chorioamnionitis was significantly higher than that in RDS-complicated neonates
without chorioamnionitis. Maternal administration of glucocorticoid suppressed
the IL-6 concentrations in the cord sera of fetuses with chorioamnionitis. The
fetuses without chorioamnionitis who suffered from RDS even after maternal
glucocorticoid administration showed a similar IL-6 titre to that of RDS-affected
neonates without chorioamnionitis. Examination of the mechanism by which IL-6
decreased the incidence of fetal RDS revealed that H441-4, a human pulmonary
adenocarcinoma cell line, stimulated with recombinant (r)-IL-6 started the
synthesis of mRNA and protein of pulmonary surfactant protein (SP)-A. The present
study shows that IL-6 elevation in fetuses with chorioamnionitis promotes fetal
lung maturation by inducing SP-A synthesis, thereby decreasing the incidence of
RDS in the preterm neonates.
PMID- 11006207
TI - ESHRE guidelines for good practice in IVF laboratories. Committee of the Special
Interest Group on Embryology of the European Society of Human Reproduction and
Embryology.
AB - Education has always been a priority for the European Society of Human
Reproduction and Embryology (ESHRE). Many efforts have been dedicated to
promoting knowledge of techniques, procedures and strategies in order to ensure
use of the highest quality practices in reproductive medicine. The need to
develop a set of guidelines was a logical consequence that found its first
expression in 1990, when Focus on Reproduction (vol. 1, pp. 10-38) published the
first guidelines which were distributed among the membership. Five years later a
new, more complete edition with several novel techniques and developments
appeared in Human Reproduction (vol. 10, pp. 1246-1271). Both have proved to be
invaluable references. Five more years have now passed. The necessity to produce
current guidelines for good IVF laboratory practice has provided the strongest
motivation. This originated from the increasing awareness that embryologists have
a duty to prevent unintentional incidents that might result from poor practice in
the laboratory. Therefore, the Embryology Special Interest Group (SIG) undertook
to draw up guidelines aimed at giving support and guidance to the laboratory
staff. All the aspects required to provide a safe working system were taken into
consideration by members of the SIG and their effort produced this document. We
hope that it will assist staff in achieving the best clinical outcome for their
patients.
PMID- 11006208
TI - Recruitment of only cytomegalovirus (CMV) negative semen donors.
PMID- 11006209
TI - The double-edged ocular immune response: the Cogan lecture.
PMID- 11006210
TI - Adipogenesis in thyroid eye disease.
AB - PURPOSE: Adipogenesis contributes to the pathogenesis of thyroid eye disease
(TED). Thyrotropin receptor (TSHR) transcripts are present in orbital fat. This
study was conducted to determine whether they are expressed as functional
protein, and if so, whether this is restricted to TED orbits or to a particular
stage in adipocyte differentiation. METHODS: Samples of fat were obtained from 18
TED-affected orbits and 4 normal orbits, and 9 were obtained from nonorbital
locations. Frozen sections were examined by immunocytochemistry using monoclonal
antibodies specific for the human TSHR. Samples were disaggregated and the
preadipocytes separated from the mature by differential centrifugation and
cultured in serum-free or DM and examined for morphologic changes, oil red O and
TSHR staining, and TSH-induced cyclic adenosine monophosphate (cAMP) production.
RESULTS: Marked immunoreactivity was observed in frozen sections from all three
TED samples and faint staining in both normal orbital fat samples. In vitro, 1%
to 5% of preadipocytes displayed TSHR immunoreactivity in five of six TED and two
of three normal orbital samples and in three of five nonorbital samples.
Differentiation, was induced in all 14 orbital samples. Three of four nonorbital
samples contained occasional differentiated cells. Fifty percent to 70% of
differentiating cells demonstrated receptor immunoreactivity. Two of three TED
and four of four nonorbital preadipocytes in DM and/or mature adipocytes
displayed a TSH-mediated increase in cAMP. CONCLUSIONS: The results indicate that
orbital fat TSHR transcripts are expressed as protein, which can be functional.
This is not aberrant in TED orbits, although expression may be upregulated. The
majority of preadipocytes undergoing differentiation express the receptor,
indicating a key role for this population in one mechanism for increasing orbital
volume.
PMID- 11006211
TI - MRI dynamic color mapping: a new quantitative technique for imaging soft tissue
motion in the orbit.
AB - PURPOSE: To investigate both feasibility and clinical potential of magnetic
resonance imaging-dynamic color mapping (MRI-DCM) in measuring the motion of soft
tissues in the orbit and in the diagnosis of orbital disorders by detecting
changes in motion. METHODS: Sequences of MRI scans were acquired (acquisition
time, 5 seconds) in a shoot-stop manner, while the patient fixated at a sequence
of 13 gaze positions (8 degrees intervals). Motion was quantified off-line (in
millimeters per degree of gaze change) using an optical flow algorithm. The
motion was displayed in a color-coded image in which color saturation of a pixel
shows the displacement and the hue the displacement's orientation. Six healthy
volunteers and four patients (two with an orbital mass and two with acrylic ball
implant after enucleation) were studied. RESULTS: The technique was found to be
clinically feasible. For a gaze change of 1 degrees, orbital tissues moved
between 0.0 and 0.25 mm/deg, depending on the type of tissue and location in the
orbit. In the patients with an orbital mass, motion of the mass was similar to
that of the medial rectus muscle, suggesting disease of muscular origin. In the
enucleated orbits, soft tissue motion was decreased. One eye showed attachment of
the optic nerve to the implant, which could be verified by biopsy. CONCLUSIONS:
MRI-DCM allows noninvasive and quantitative measurement of soft tissue motion and
the changes in motion due to pathologic conditions. In cases in which the
diagnosis of a tumor in the apex is in doubt, it may reduce the need for biopsy.
In contrast to static computed tomographic (CT) scans and MRIs, it can
differentiate between juxtaposition and continuity and may be a new and promising
tool in the differential diagnosis of intraorbital lesions.
PMID- 11006212
TI - Expression regulation of hyaluronan synthase in corneal endothelial cells.
AB - PURPOSE: Our previous study showed that hyaluronan synthase (HAS), the enzyme
protein of hyaluronan (HA) biosynthesis, is expressed in ocular tissues including
the corneal endothelium. In the current study, the mechanism that regulates HAS
expression in bovine corneal endothelial cells (BCECs) was investigated. METHODS:
Cultured BCECs were used. HAS expression in BCECs at the mRNA level was detected
by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot
analysis. The effects of transforming growth factor (TGF)-beta and platelet
derived growth factor (PDGF)-BB on HAS expression were examined by quantitative
RT-PCR. The involvement of the Smad family (intracellular signal transducer of
TGF-beta) was also investigated. The expression of HAS in BCECs at the protein
level was confirmed by immunocytochemistry and Western blot analysis. RESULTS:
Three HAS isoforms in BCECs were expressed at the mRNA level. The transcriptional
sizes of each HAS in BCECs were 4.9 kb for HAS1, 2.8 kb for HAS2, and 1.6 kb for
HAS3. The expression of HAS2 at the mRNA level was stimulated by TGF-beta1 and/or
PDGF-BB treatment. In contrast, HAS1 and HAS3 expression was not affected by
these growth factors. The additive effects of TGF-beta1 and PDGF-BB were observed
in the stimulation of the expression levels of HAS2. HAS2 upregulation by these
growth factors was also detected by Western blot analysis. The stimulation of the
expression of HAS2 at the mRNA level by TGF-beta was accelerated by the
overexpression of Smad2, Smad3, and Smad4 and inhibited by that of Smad7, all of
which were confirmed to be involved in the signal transduction from TGF-beta
through HAS expression. CONCLUSIONS: Although three HAS isoforms were expressed
in the corneal endothelial cells, the expression of HAS2 was upregulated by TGF
beta1 and/or PDGF-BB. HAS2 expression was regulated by TGF-beta through Smad
family members.
PMID- 11006213
TI - HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in
a transgenic model.
AB - PURPOSE: To investigate the function and pathogenicity of HRG4, a photoreceptor
synaptic protein homologous to the Caenorhabditis elegans neuroprotein UNC119.
METHODS: HRG4 was screened for mutations in patients with various retinopathies,
and a transgenic mouse model was constructed and analyzed based on a mutation
found. RESULTS: A heterozygous premature termination codon mutation was found in
a 57-year-old woman with late-onset cone-rod dystrophy. In some transgenic mice
carrying the identical mutation, age-dependent fundus lesions developed
accompanied by electroretinographic changes consistent with defects in
photoreceptor synaptic transmission (depressed b-wave, normal c-wave), and
retinal degeneration occurred with marked synaptic and possible transsynaptic
degeneration. CONCLUSIONS: HRG4, the only synaptic protein known to be highly
enriched in photoreceptor ribbon synapses, is now shown to be pathogenic when
mutated.
PMID- 11006214
TI - A new betaA1-crystallin splice junction mutation in autosomal dominant cataract.
AB - PURPOSE: To map the locus for autosomal dominant cataracts (ADCs) in a Brazilian
family using candidate gene linkage analyses, describe the clinical variability,
and identify potential mutations in the human betaA1-crystallin gene (CRYBA1), a
candidate gene identified through linkage studies demonstrating cosegregation
with markers on chromosome 17. METHODS: Members of a Brazilian family with ADC
were studied. Clinical examinations and linkage analyses with polymerase chain
reaction (PCR) polymorphisms of 22 anonymous markers and 2 within the
neurofibromatosis type 1 gene were performed; two-point lod scores were
calculated. DNA sequences of all 6 exons and 12 exon-intron boundaries of the
betaA1-crystallin gene, a proximal candidate gene mapped to 17q11.1-q12 in one
unaffected and two affected individuals, were screened and new variants assessed
for cosegregation with the disease. RESULTS: Affected individuals exhibited
variable expressivity of pulverulent opacities in the embryonal nucleus and
sutures; star-shaped, shieldlike, or radial opacities in the posterior embryonal
nucleus; and/or midcortical opacities. All known loci for ADC in this family on
chromosomes 1 and 13 were excluded. A positive lod score on chromosome 17 was
calculated. This ADC locus was mapped to two potential regions on the long arm
with an intervening recombination. The only known candidate gene in these regions
was betaA1-crystallin. Three previously unreported single nucleotide variants
were found in this gene, one in the donor splice junction site of intron C. This
variant was found in all affected members and is presumed to be the causative
mutation. CONCLUSIONS: An ADC locus was mapped in a Brazilian family with
variable expressivity to either 17q23.1-23.2 or 17q11.1-12 based on linkage
analyses. Analyses of DNA sequences of the betaA1-crystallin gene in this family
revealed three new variants, one of which is within a donor splice junction and
cosegregates with affected members.
PMID- 11006215
TI - Ultrastructural and molecular analysis of Bowman's layer corneal dystrophies: an
epithelial origin?
AB - PURPOSE: Two mutations (R555Q and R124L) in the BIGH3 gene have been described in
anterior or Bowman's layer dystrophies (CDB). The clinical, molecular, and
ultrastructural findings of five families with CDB was reviewed to determine
whether there is a consistent genotype:phenotype correlation. METHODS:
Keratoplasty tissue from each patient was examined by light and electron
microscopy (LM and EM). DNA was obtained, and exons 4 and 12 of BIGH3 were
analyzed by polymerase chain reaction and single-stranded conformation
polymorphism/heteroduplex analysis. Abnormally migrating products were analyzed
by direct sequencing. RESULTS: In two families with type I CDB (CDBI), the R124L
mutation was defined. There were light and ultrastructural features of
superficial granular dystrophy and atypical banding of the "rod-shaped bodies"
ultrastructurally. Patients from three families with "honeycomb" dystrophy were
found to carry the R555Q mutation and had characteristic features of Bowman's
dystrophy type II (CDBII). CONCLUSIONS: There is a strong genotype:phenotype
correlation among CBDI (R124L) and CDBII (R555Q). LM and EM findings suggest that
epithelial abnormalities may underlie the pathology of both conditions. The
findings clarify the confusion over classification of the Bowman's layer
dystrophies.
PMID- 11006216
TI - Ascorbic acid concentration and total antioxidant activity of human tear fluid
measured using the FRASC assay.
AB - PURPOSE: To evaluate a novel method (FRASC) for total ferric reducing
(antioxidant) activity and ascorbic acid concentration applied to human tears, to
investigate the stability of ascorbic acid, and to determine the antioxidant
status of human reflex tears. METHODS: Linearity, sensitivity, and precision of
FRASC and ascorbic acid loss during 7 days' storage were assessed; total
antioxidant activity and ascorbic acid and uric acid concentrations of reflex
tears from 47 healthy subjects were measured. RESULTS: FRASC has good precision,
linearity, and sensitivity. Ascorbic acid is stable for at least 7 days at
moderately acidic pH (pH 3.6) and low temperature. Total antioxidant activity and
ascorbic acid and uric acid concentrations (mean +/- SD) in reflex tears were 409
+/- 162, 23 +/- 9.6, and 68 +/- 46 microM, respectively. Ascorbic acid and uric
acid constituted around half the total antioxidant activity measured. There was a
significant correlation between uric acid and total antioxidant activity (r =
0.754; P: < 0.0001). Men had significantly (P: = 0.0045) higher tear ascorbic
acid concentrations than women. CONCLUSIONS: FRASC is suitable for measuring
total antioxidant activity and ascorbic acid in human tears. Further clinical
study is needed to investigate the male-female difference seen, to characterize
the remaining 50% antioxidant activity, and to investigate the effects of
environmental conditions, antioxidant supplementation, age, and ocular disease on
tear antioxidant status.
PMID- 11006217
TI - Elevated levels of proteolytic enzymes in the aging human vitreous.
AB - PURPOSE: To identify whether aging of human vitreous is accompanied by an
elevation in degradative enzymes within the tissue. METHODS: Human vitreous
samples from donors aged 10 to 88 years were placed in two groups based on donor
age of less than or more than 50 years. Homogenized samples were analyzed by
gelatin substrate zymography for matrix metalloproteinases (MMP). Serine
proteinases were detected by casein substrate zymography, and a specific antibody
was used to confirm the identity of, and to quantify, the serine proteinase,
plasmin. RESULTS: Progelatinase A (ProMMP-2) was present in all the vitreous
samples but did not show an age-related increase. MMP-2 was also present at low
levels. Progelatinase B (ProMMP-9) was found in approximately 80% of samples
analyzed, but neither its presence nor level of activity was age dependent. Of
the serine proteinase activities detected, an enzyme of approximately 80 kDa was
identified by Western blot analysis as plasmin(ogen). Quantitative analysis
revealed a significant increase in plasmin(ogen) with age. CONCLUSIONS: This
study shows there is an age-related increase in potential degradative activity in
human vitreous that may be responsible for degenerative changes such as vitreous
liquefaction. The data suggest that increased levels of these enzymes precede, or
are indicative of, underlying ocular disease in some individuals.
PMID- 11006218
TI - A novel resource for the study of genes expressed in the adult human retina.
AB - PURPOSE: To reconstruct the transcriptional profile of the human adult retina and
the genomic map of the genes expressed in this tissue. METHODS: Original software
was used for the retrieval and analysis of records from UniGene
(http://www.ncbi.nlm.nih. gov/UniGene/) pertaining to selected cDNA libraries
from adult human retina. RESULTS: The 4974 genes reported so far to be expressed
in retina were included in a catalog available on the Internet. For each entry,
an estimation of the level of expression of the corresponding gene in the retina
was provided. A high-resolution genomic map of the human retina was built up by
inclusion of 3152 genes showing a precise and unique map assignment. The
correspondence was established between 53 gene-orphan retinal diseases and
clusters of genes expressed in the retina. CONCLUSIONS: The in silico
reconstruction of the transcriptional profile of the adult human retina provides
preliminary information on the pattern of genomic expression in this tissue. The
chromosomal location of many retinal genes, combined with their expression data,
should speed up the identification of genes involved in retinal diseases.
PMID- 11006219
TI - Changing views on open-angle glaucoma: definitions and prevalences--The Rotterdam
Study.
AB - PURPOSE: To create a quantitative basis for diagnostic criteria for open-angle
glaucoma (OAG), to propose an epidemiologic definition for OAG based on these,
and to determine the prevalence of OAG in a general white population. METHODS: Of
the 7983 subjects 55 years of age or older participating in the population-based
Rotterdam Study, 6756 subjects participated in the ophthalmic part of this study
(6281 subjects living independently and 475 in nursing homes). The criteria for
the diagnosis of OAG were based on ophthalmoscopic and semiautomated Imagenet
estimations of the optic disc such as vertical cup-to-disc ratio (VCDR), minimal
width of neural rim, or asymmetry in VCDR between both eyes, and visual field
testing with kinetic Goldmann perimetry. All criteria for the diagnosis of OAG
were assessed in a masked way independently of each other. RESULTS: Mean VCDR on
ophthalmoscopy was 0.3 and with Imagenet 0.49, and the 97.5th percentile for both
was 0.7. The prevalence of glaucomatous visual field defects was 1.5%. Overall
prevalence of definite OAG in the independently living subjects was 0.8% (95%
confidence interval [CI] 0.6, 1.0; 50 cases). Prevalence of OAG in men was double
that in women (odds ratio 2.1; 95% CI 1.2, 3.6). Different commonly used criteria
for diagnosis of OAG resulted in prevalence figures ranging from 0.1% to 1.2%.
CONCLUSIONS: The overall prevalence of OAG in the present study was comparable to
most population-based studies. However, prevalence figures differed by a factor
of 12 when their criteria for OAG were applied to this population. A definition
for definite OAG is proposed: a glaucomatous optic neuropathy in eyes with open
angles in the absence of history or signs of secondary glaucoma characterized by
glaucomatous changes based on the 97.5 percentile for this population together
with glaucomatous visual field loss. In the absence of the latter or of a visual
field test, it is proposed to speak of probable OAG based on the 99.5th or
possible OAG based on the 97.5th percentiles of glaucomatous disc changes for a
population under study.
PMID- 11006220
TI - Influence of lutein supplementation on macular pigment, assessed with two
objective techniques.
AB - PURPOSE: Macular pigment (MP) may protect against age-related macular
degeneration. This study was conducted to determine the extent of changes in the
macular pigment density as a consequence of oral supplementation with lutein. A
second purpose was to compare two objective measurement techniques. METHODS: In
the first technique, reflectance maps were made with a scanning laser
ophthalmoscope. Digital subtraction of log reflectance maps and comparison
between the foveal area and a 14 degrees temporal site provided MP density
estimates. In the second technique, spectral fundus reflectance of the fovea was
measured with a fundus reflectometer and analyzed with a detailed optical model,
to arrive at MP density values. Eight subjects participated in this study. They
took 10 mg lutein per day for 12 weeks. Plasma lutein concentration was measured
at 4-week intervals. RESULTS: After 4 weeks, mean blood level of lutein had
increased from 0.18 to 0.90 microM. It stayed at this level throughout the intake
period and declined to 0.28 microM 4 weeks after termination. Measurement of the
density of MP showed a within-subject variation of 10% with MP maps and 17% with
spectral reflectance analysis. MP density showed a mean linear 4-week increase of
5.3% (P: < 0.001) and 4.1% (P: = 0. 022), respectively. CONCLUSIONS:
Supplementation with lutein significantly increased the density of the MP.
Analyzing reflectance maps with a scanning laser ophthalmoscope provided very
reliable estimates of MP.
PMID- 11006221
TI - Monocular versus binocular visual acuity as measures of vision impairment and
predictors of visual disability.
AB - PURPOSE: To examine the relationship between monocular and binocular visual
acuities as predictors of visual disability in a population-based sample of
individuals 65 years of age and older. METHODS: Two thousand five hundred twenty
community-dwelling residents of Salisbury, Maryland, between the ages of 65 and
84 years of age were recruited for the study. Corrected visual acuity was
measured monocularly and binocularly using ETDRS charts. Reading speed, face
discrimination, and self-reported difficulty with visual tasks were also
determined. RESULTS: Binocular acuity is predicted with reasonable accuracy by
acuity in the better eye alone, but not by the widely used American Medical
Association (AMA) weighted-average algorithm. The AMA algorithm significantly
underestimates binocular acuity when the interocular acuity difference exceeds
one line. Monocular acuity and binocular acuity were significantly better
predictors of reading speed than the AMA weighted score or a recently proposed
Functional Vision Score (FVS). Monocular acuity in the better eye, binocular
acuity, and the AMA and FVS algorithms were equally good predictors of self
reported vision disability. None of the acuity measures were good predictors of
face recognition ability. CONCLUSIONS: The binocular acuities of older
individuals can be inferred from measures of monocular acuity. There is little
evidence for binocular inhibition when the monocular acuities in the two eyes are
unequal, as opposed to the widely used AMA algorithm for computing binocular
visual impairment. For tasks that are strongly associated with visual acuity,
such as reading, this association can be captured from measures of monocular
acuity and does not require separate assessment of binocular acuity.
PMID- 11006222
TI - Photochemical keratodesmos for repair of lamellar corneal incisions.
AB - PURPOSE: To determine the efficacy of photochemical keratodesmos (PKD) for
closing surgical incisions in the cornea of enucleated rabbit eyes compared with
that achieved using sutures and self-sealing incisions. METHODS: A 3.5-mm
incision, at an angle parallel to the iris, was made in the cornea of enucleated
New Zealand White rabbit eyes. The intraocular pressure required to cause leakage
(IOP(L)) from the untreated incision was then recorded. Photochemical
keratodesmos treatment was then performed by application of a dye, Rose Bengal
(RB), in saline solution to the surfaces of the incision wound, followed by laser
irradiation at 514 nm from an argon ion laser. Immediately after treatment, the
IOP(L) was measured. Both dose and laser irradiance dependencies were studied in
five or more eyes for each condition and appropriate control eyes. The IOP(L)s
were compared with those obtained using conventional interrupted 10-0 nylon
sutures. Other dyes were tested in a similar fashion. RESULTS: The IOP(L) of 300
mm Hg was obtained using a fluence of 1270 J/cm(2) with an irradiance of 1.27
W/cm(2) (laser exposure time, 16 minutes 40 seconds). No sealing was observed
using dye or light alone where control pressures of approximately 30 mm Hg were
found. At higher dose (1524 J/cm(2)) and irradiance (3.82 W/cm(2); 6 minutes 35
seconds), PKD was less effective, which may be attributable to thermal effects.
PKD produced IOP(L)s similar to those in closure by sutures. Other dyes such as
riboflavin-5-phosphate and N:-hydroxy-pyridine thione also produced efficient
bonding after PKD. Nonphotochemically active dyes did not produce significant
increases in the IOP(L) at which leakage occurred. CONCLUSIONS: The increase in
IOP(L) after PKD treatment, comparable with that with sutures, in enucleated
rabbit eyes demonstrates the feasibility of this technique ex vivo.
PMID- 11006223
TI - The role of cytotoxic T lymphocytes in corneal allograft rejection.
AB - PURPOSE: Immunologic rejection constitutes a major barrier to the success of
allogeneic corneal transplants, but the specific mediators and mechanisms of
graft rejection are poorly understood. Several studies have implicated cytotoxic
T-lymphocyte (CTL) responses, typically associated with CD8(+) T cells, in
promoting corneal graft rejection. This study sought to test the hypothesis that
CTLs are essential in promoting corneal graft rejection. METHODS: BALB/c donor
corneas were grafted orthotopically onto C57BL/6, perforin knockout, or CD8(+) T
cell knockout mice. The tempo and incidence of graft rejection were observed for
each group. In separate experiments, donor-specific CTL and delayed-type
hypersensitivity (DTH) responses were tested at the time of graft rejection by a
standard chromium release assay and an ear swelling assay, respectively. RESULTS:
Perforin knockout and CD8(+) T-cell knockout mice were as effective as wild-type
C57BL/6 control mice in rejecting BALB/c donor corneas. Furthermore, animals in
all three groups were found to develop robust donor-specific DTH, not CTL,
responses at the time of graft rejection. Histopathologically, the rejected
corneas from all three groups contained a predominantly mononuclear cellular
infiltrate. CONCLUSIONS: This study rejects the hypothesis that CD8(+) CTLs are
essential in promoting corneal graft rejection and instead further implicates
donor-specific DTH reactions as the relevant immune response during graft
failure.
PMID- 11006224
TI - The thickness of the human precorneal tear film: evidence from reflection
spectra.
AB - PURPOSE: Interferometric methods have considerable potential for studying the
thickness of layers of the human tear film and cornea because of their ability to
make noninvasive, accurate, and rapid measurements. However, previous
interferometric studies by Prydal and Danjo yielded tear thickness values near 40
and 11 microm, respectively, considerably greater than estimates made by invasive
methods of 4 to 8 microm. Using a modified version of Danjo's method,
interference effects from the tear film and cornea were studied, with the aim of
correlation with known structure and optical properties of the cornea and hence
determining the most probable value of tear film thickness. METHODS: Reflectance
spectra from the human cornea were measured at normal incidence. These spectra
show oscillations whose maxima correspond to constructive interference between
light reflected from the air surface and from some deeper surface. The frequency
of these spectral oscillations is proportional to the thickness of the layer
between the air surface and the second surface. Therefore, Fourier analysis of
reflectance spectra can be used to determine the thickness of layers of the tear
film and cornea. In the main experiment, 36 low-resolution spectra were obtained
from six normal eyes for measuring thickness up to 100 microm. Control
experiments included measurements of the time course of thickness changes and
high-resolution spectra for measuring thickness up to 1000 microm. RESULTS: For
the main experiment, in the thickness range 1 to 100 microm, the strongest peak
in the Fourier transform was near 3 microm (range, 1.5-4.7 microm) beneath the
air surface. In the range 20 to 100 microm, the strongest peak was near 55 microm
(range, 50-59 microm) for all 36 spectra; none were in Prydal's range near 40
microm. This 55-microm peak is consistent with a reflection from the basement
membrane of the epithelium. Time course measurements after a blink show that the
3-microm peak is not an artifact. High-resolution spectra gave a peak near 510
microm, corresponding to the complete thickness of the cornea (plus tear film).
This peak had a contrast similar to that of the 3-microm peak. CONCLUSIONS: These
studies did not confirm Prydal's estimate of approximately 40 microm. Nor were
there prominent peaks near Danjo's value of approximately 11 microm, except in
cases of probable reflex tears. Because the reflection at the aqueous-mucus
boundary would be expected to be weaker than that from the epithelial surface,
the 3-microm peak is unlikely to correspond to the aqueous layer (rather than the
complete tear film). The proposal that the 3-microm peak corresponds to a
reflection from the front of the cornea is supported by the demonstration of a
peak of similar contrast from the back of the cornea. Thus, the current evidence
consistently supports a value of approximately 3 microm for the thickness of the
human precorneal tear film.
PMID- 11006225
TI - Apoptosis in shed human corneal cells.
AB - PURPOSE: To determine whether shear forces applied to the corneal epithelium by
the repeated insertion and removal of a hydrogel contact lens alter the size and
number of cells removed and to determine the contribution of apoptosis to this
process. METHODS; Human corneal cells were collected from eight healthy subjects
by sequential contact lens cytology (20 lens insertions and removals). Collected
cells were stained with acridine orange for counting and measurement of cell
size. In a separate experiment, collected cells were fixed and stained with TdT
mediated dUTP nick-end labeling (TUNEL) or labeled immediately after collection
using annexin V. Hoechst stain and propidium iodide (PI) were used as nuclear
counterstains. The proportion of cells labeled with acridine orange, TUNEL, and
annexin V was quantified by fluorescence microscopy. RESULTS; The number of cells
increased in later collections, and cells were smaller. The mean number of
positively stained cells using TUNEL was 57%. Annexin V labeling on unfixed fresh
samples showed a mean of 64%, with an increase in later collections. Apoptotic
bodies were observed in very few cells. In most cells the nucleus and cytoplasmic
membrane were intact. Structures were observed in which nuclei were missing
(Hoechst negative) but in which cytoplasm had the size and appearance of whole,
nucleated cells. These structures (cell ghosts) increased in number along with
the increase in nucleated cells in later collections. CONCLUSIONS: The sequential
removal of a soft contact lens caused a progressive increase in the number of
cells collected from the surface and a progressive decrease in their size. The
majority of nucleated cells removed by a contact lens were apoptotic in the sense
of being positively labeled by TUNEL and annexin V. Morphologically they differed
from classically apoptotic cells, in that cells showed an intact nuclear
structure and no discernible apoptotic bodies. They could represent a last stage
in a pathway of cell differentiation in which frictional forces induced by the
removal of the contact lens activate the apoptotic program and cause the cell to
be shed. There is also a pathway in which cells lose their nuclei before leaving
the epithelial surface.
PMID- 11006226
TI - Corneal opacity in lumican-null mice: defects in collagen fibril structure and
packing in the posterior stroma.
AB - PURPOSE: Gene targeted lumican-null mutants (lum(tm1sc)/lum(tm1sc)) have cloudy
corneas with abnormally thick collagen fibrils. The purpose of the present study
was to analyze the loss of transparency quantitatively and to define the
associated corneal collagen fibril and stromal defects. METHODS: Backscattering
of light, a function of corneal haze and opacification, was determined regionally
using in vivo confocal microscopy in lumican-deficient and wild-type control
mice. Fibril organization and structure were analyzed using transmission electron
microscopy. Biochemical approaches were used to quantify glycosaminoglycan
contents. Lumican distribution in the cornea was elucidated
immunohistochemically. RESULTS; Compared with control stromas, lumican-deficient
stromas displayed a threefold increase in backscattered light with maximal
increase confined to the posterior stroma. Confocal microscopy through-focusing
(CMTF) measurement profiles also indicated a 40% reduction in stromal thickness
in the lumican-null mice. Transmission electron microscopy indicated significant
collagen fibril abnormalities in the posterior stroma, with the anterior stroma
remaining relatively unremarkable. The lumican-deficient posterior stroma
displayed a pronounced increase in fibril diameter, large fibril aggregates,
altered fibril packing, and poor lamellar organization. Immunostaining of wild
type corneas demonstrated high concentrations of lumican in the posterior stroma.
Biochemical assessment of keratan sulfate (KS) content of whole eyes revealed a
25% reduction in KS content in the lumican-deficient mice. CONCLUSIONS: The
structural defects and maximum backscattering of light clearly localized to the
posterior stroma of lumican-deficient mice. In normal mice, an enrichment of
lumican was observed in the posterior stroma compared with that in the anterior
stroma. Taken together, these observations indicate a key role for lumican in the
posterior stroma in maintaining normal fibril architecture, most likely by
regulating fibril assembly and maintaining optimal KS content required for
transparency.
PMID- 11006227
TI - Erk and PI-3 kinase are necessary for collagen binding and actin reorganization
in corneal epithelia.
AB - PURPOSE: It was recently shown that phosphatidylinositol-(PI)3 kinase is
upregulated in wounded rabbit corneal epithelia. Extracellular signal-regulated
kinase (erk)-1 and -2 proteins and PI-3 kinase were activated in embryonic
corneal epithelia after 1-hour stimulation by type I collagen. In the current
investigation specific inhibitors of PI-3 kinase and mitogen-activated kinase
kinase (MEK-1 kinase) were used to determine the role of these signaling
molecules in actin reorganization and collagen binding to isolated sheets of
corneal epithelial tissue. METHODS: Effects of specific PI-3 kinase and MEK-1
inhibitors (LY294002, PD98059, respectively) were investigated in embryonic
corneal epithelial tissues. Avian embryonic corneal epithelia were isolated as
tissue sheets, organ cultured in the presence of these specific inhibitors, and
stimulated with type I collagen. The tissues were evaluated for collagen
stimulated actin reorganization, erk-1 and -2 and PI-3 kinase activity, total
filamentous actin accumulation, and collagen binding. RESULTS: The MEK-1
inhibitor PD98059 decreased erk-1 and -2 phosphorylation and blocked actin
reorganization in a dose-dependent manner. The PI-3 kinase 85-kDa subunit was
decreased 25% in LY294002-treated tissue, and collagen binding also decreased
significantly in tissues treated with MEK-1 and PI-3 kinase inhibitors compared
with control tissues. In addition, both inhibitors blocked actin cortical mat
reorganization. CONCLUSIONS; PI-3 kinase and erk-1 and -2 signaling pathways are
activated and necessary for collagen binding and integrin-mediated actin
reorganization in embryonic avian corneal epithelium.
PMID- 11006228
TI - Localization of thrombomodulin in the anterior segment of the human eye.
AB - PURPOSE: To localize thrombomodulin (TM) in the anterior segment of the human
eye. TM is a vascular endothelial cell surface glycoprotein that acts as a
cofactor for the thrombin-catalyzed activation of the anticoagulant protease
zymogen, protein C. METHODS: Immunohistochemical methods were used to detect TM
expression in corneal epithelial cells, the lens epithelial cells, and other
cells in the anterior segment of the eye. The expression of TM was also examined
in cultured human corneal epithelial cells. RESULTS: TM was expressed in corneal
epithelial cells, corneal endothelial cells, and nonpigmented ciliary epithelial
cells, which are in direct contact with the aqueous humor. TM was also expressed
in cultured corneal epithelial cells and showed cofactor activity. The amount of
the antigen in the cultured corneal cells was approximately one tenth of that in
human umbilical vein endothelial cells, but its specific cofactor activity (75%)
was comparable to that of TM in human umbilical vein endothelial cells. The
trabecular meshwork and endothelial cells lining Schlemm's canal also showed
positive staining for TM. CONCLUSIONS: The TM in the cells that are in contact
with the aqueous humor appears to be involved in maintaining the fluidity of the
aqueous humor. In contrast, TM in cells that are not in contact with the aqueous
humor may function in regulating cell proliferation and/or differentiation.
PMID- 11006229
TI - The distribution of myosin heavy chain isoforms among rat extraocular muscle
fiber types.
AB - PURPOSE: To determine the distribution of myosin heavy chain isoforms in each
extraocular muscle (EOM) fiber type. METHODS: Serial sections of adult rat EOMs
were stained with isoform-specific monoclonal antibodies against an array of
myosin heavy chains. Immunofluorescent antibody staining of whole adult rat EOMs,
examined by confocal microscopy, demonstrated the longitudinal variations of
isoforms along individual fibers. RESULTS: Each global fiber type reacted
predominantly with a single isoform-specific antibody and showed no longitudinal
variation. Two major orbital fibers were defined, and both contained multiple
myosin heavy chains. Both orbital singly and multiply innervated fibers stained
proximal and distal to the neuromuscular junction with antibody to embryonic
myosin heavy chain, but this isoform was sharply and completely excluded from the
domain of the neuromuscular junction. Orbital singly innervated fibers also
contained the EOM-specific isoform at the neuromuscular junction. Orbital
multiply innervated fibers did not contain the EOM-specific isoform, but
additionally contained a slow isoform along their entire length. CONCLUSIONS:
Adult rat EOMs show unique fiber types with arrangements of myosin heavy chain
isoforms not seen in other skeletal muscles. Moreover, unique cellular mechanisms
must exist to target each isoform to its proper domain along individual orbital
fibers.
PMID- 11006230
TI - Histologic effect of mitomycin C on strabismus surgery in the rabbit.
AB - PURPOSE: To evaluate the efficiency of mitomycin C (MMC) in limiting the
postoperative inflammatory response and scarring after strabismus surgery.
METHODS: A prospective, two-stage, masked, controlled trial was conducted. In the
first stage, the inflammatory response at the extraocular muscle reattachment
site was increased after inferior rectus recession in eight rabbits. In the
second stage, MMC (0.4 mg/ml) was applied during surgery to the eyes of 22
rabbits with inferior rectus recession. As a control, contralateral eyes were
treated with saline solution. Seven weeks later, exenteration was performed, and
the sites of muscle reattachment were processed for histologic examinations. The
sums of the areas of the granulomas in the extraocular muscle reattachment sites
of control and treated eyes were compared. RESULTS: There was no significant
inhibitory effect of MMC on the inflammatory response of treated eyes compared
with that of control eyes. CONCLUSIONS: The intraoperative use of MMC (0.4 mg/ml)
was not effective in controlling the postoperative inflammatory response in
rabbit eyes after extraocular muscle surgery. These data do not support the
hypothesis that MMC reduces postoperative adhesions after strabismus surgery.
PMID- 11006231
TI - Acute effects of the skeletal muscle-specific immunotoxin ricin-mAb 35 on
extraocular muscles of rabbits.
AB - PURPOSE: To determine the acute histologic and ultrastructural effects of a
recently developed muscle-specific immunotoxin, ricin-mAb 35. METHODS: Graduated
doses of ricin-mAb 35, composed of ricin conjugated to a monoclonal antibody
against the nicotinic acetylcholine receptor of skeletal muscle, were injected
into one superior rectus muscle in rabbits. After 3, 7, and 14 days, both
superior rectus muscles were removed and prepared for electron microscopy and
histologic examination, by using a number of immunohistochemical markers to
identify inflammatory cell infiltration, muscle fiber loss, and muscle
regeneration. RESULTS: Myotoxicity of the ricin-mAb 35 was focal and dose
related. At the highest dose tested, there was substantial inflammatory cell
infiltrate by 3 days, which largely disappeared by 7 days. Significant muscle
loss was apparent by 7 days after ricin-mAb 35 treatment. Both the inflammatory
reaction and muscle fiber loss were confined to the immediate injection site.
Surrounding muscle appeared to be normal. At 14 days after treatment, early signs
of muscle regeneration were evident within the tissue sections. No evidence of
orbital or systemic toxicity was seen in any animal. CONCLUSIONS: Direct
injection of ricin-mAb 35 into the extraocular muscles of rabbits results in a
dose-related focal injury to the muscles, with a self-limited inflammatory
component and significant muscle fiber loss. This novel immunotoxin may be useful
in the treatment of strabismus if chronic studies show a sustained histologic and
electrophysiologic effect.
PMID- 11006232
TI - Infant hyperacuity for radial deformation.
AB - PURPOSE: Poor response rates and/or the confounding of motion and offset
responses make it difficult to interpret results of previous studies of infant
hyperacuity. The aim of the present study was to design a protocol that overcomes
these limitations and to investigate the normal maturation of hyperacuity.
METHODS: Hyperacuity of 31 healthy term infants aged 4 to 12 months was measured
using radial deformation of static circular D4 patterns with a two-alternative,
forced-choice, preferential-looking (FPL) protocol and maximum likelihood
threshold estimation. FPL grating resolution acuity was assessed on the same
visit. RESULTS: Both hyperacuity and resolution acuity were 1.1 to 1.2 logMAR (12
16 minutes arc) at 4 months of age. Hyperacuity improved rapidly to approximately
0.3 logMAR (2.0 minutes arc) by 9 to 12 months of age. This 0.9 log unit
improvement in the hyperacuity still leaves the 12-month-old infant at a level
0.4 log unit poorer than adults' thresholds. Resolution acuity improved more
gradually to approximately 0.7 logMAR (5 minutes arc) by 9 to 12 months of age.
This 0.4 log unit improvement leaves the 12-month-old infant at a level 0.6 log
unit poorer than adults' resolution acuity. CONCLUSIONS: Hyperacuity measured via
radial deformation thresholds matures very rapidly between 4 and 6 months of age
and continues to mature more slowly throughout infancy and into early childhood.
The radial deformation protocol may provide a sensitive index for detecting and
monitoring abnormalities in spatial vision in cases of infantile esotropia.
PMID- 11006233
TI - Effect of general anesthetics on IOP in rats with experimental aqueous outflow
obstruction.
AB - PURPOSE: To determine the effect of several common general anesthetics on
intraocular pressure (IOP) after experimental aqueous outflow obstruction in the
rat. METHODS: A single episcleral vein injection of hypertonic saline was used to
sclerose aqueous humor outflow pathways and produce elevated IOP in Brown Norway
rats. Animals were housed in either standard lighting or a constant low-level
light environment. Awake IOPs were determined using a TonoPen (Mentor, Norwell,
MA) immediately before induction of anesthesia by either isoflurane, ketamine, or
a mixture of injectable anesthetics (xylazine, ketamine, and acepromazine). For
each anesthetic, IOPs were measured immediately after adequate sedation (time 0)
and at 5-minute intervals, up to 20 minutes. RESULTS; Awake IOPs ranged from 18
to 52 mm Hg. All anesthetics resulted in a statistically significant (P: < 0.01)
reduction in measured IOP at every duration of anesthesia when compared with the
corresponding awake IOP. With increasing duration of anesthesia, measured IOP
decreased approximately linearly for both the anesthetic mixture and isoflurane.
However, with ketamine, IOP declined to 48% +/- 11% (standard lighting) and 60%
+/- 7% (constant light) of awake levels at 5 minutes of anesthesia, where it
remained stable. In fellow eyes, the SD of the mean IOP in animals under
anesthesia was always greater than the corresponding SD of the awake mean.
Anesthesia's effects in normal eyes and eyes with elevated IOP were
indistinguishable. CONCLUSIONS: All anesthetics resulted in rapid and substantial
decreases in IOP in all eyes and increased the interanimal variability in IOPs.
Measurement of IOP in awake animals provides the most accurate documentation of
pressure histories for rat glaucoma model studies.
PMID- 11006234
TI - Localization of MYOC transcripts in human eye and optic nerve by in situ
hybridization.
AB - PURPOSE: To evaluate MYOC (myocilin) gene expression at the RNA level in normal
intact human eyes and optic nerve using in situ hybridization. METHODS: Normal
human eyes and optic nerves from donors 62 to 83 years of age with no history of
glaucoma were fixed, embedded in paraffin, and sectioned. Sections were
hybridized with (35)S-labeled sense and antisense riboprobes derived from a full
length MYOC cDNA. RESULTS: High levels of MYOC expression were observed
throughout the trabecular meshwork as well as in the most anterior nonfiltering
meshwork (Schwalbe's line), in the scleral spur, and in the endothelial lining of
Schlemm's canal. MYOC transcripts were also detected in the anterior corneal
stroma, in the ciliary muscle, beneath the anterior border of the iris, in the
iris stroma, and in the sclera. Expression in the retrolaminar region of the
optic nerve was present in the pial septa that divide the nerve fiber bundles, in
the perivascular connective tissue surrounding the central retinal vessels, and
in the dura mater, arachnoid, and pia mater of the meningeal sheath surrounding
the optic nerve. CONCLUSIONS: MYOC gene expression in the trabecular meshwork,
Schlemm's canal, scleral spur, and ciliary muscle indicates a structural or
functional role for myocilin in the regulation of aqueous humor outflow that may
influence intraocular pressure. MYOC expression in the optic nerve suggests that
changes in the structural, metabolic, or neurotropic support of the optic nerve
may influence its susceptibility to glaucomatous damage.
PMID- 11006235
TI - The long-term fluctuation of the visual field in stable glaucoma.
AB - PURPOSE: To determine, in stable glaucoma, the characteristics of the between
examination variability of the visual field recorded with the Humphrey Field
Analyser (HFA; Humphrey Systems, Dublin, CA) using the homogeneous, LF(Ho), and
heterogeneous, LF(He), components of the long-term fluctuation (LF), thereby
providing a technique for separating progressive loss from fluctuation in
sensitivity. METHODS: The LF components were calculated using a two-factor
analysis of variance (ANOVA) with replications and were determined between each
pair of three successive HFA program 30-2 fields for each patient from two
groups, each containing 30 patients with primary open-angle glaucoma. The
interval between examinations for the first group was 6 to 9 months and for the
second group was 3 weeks. RESULTS: The group mean values for LF(Ho) ranged from
1.50 to 2.19 dB and for LF(He) from 1.70 to 2.05 dB. The average difference
between examinations was within +/-0.35 dB for each component, and the 95% limits
of agreement for the two groups, respectively, were +/- 2.31 and +/- 2.39 dB for
the LF(Ho) and +/- 2.36 and +/- 2.09 dB for the LF(He). The estimate of the 90%
confidence limit for the LF(Ho) was 3.30 dB and for the LF(He), 3.60 dB. Little
relationship was present between the LF components and the modulus differences in
mean deviation (MD), the corrected pattern SD (CPSD), or the mean MD, mean short
term fluctuation, and mean CPSD, of the two fields. CONCLUSIONS: Estimation of
the LF components and of the corresponding confidence limits yields an expression
of the normal between-examination variability of two consecutive fields that can
be used as a reliability index. A value outside the confidence limits indicates
the necessity for a confirmatory follow-up field.
PMID- 11006236
TI - Modulation of pre-mRNA splicing and protein production of fibronectin by TGF
beta2 in porcine trabecular cells.
AB - PURPOSE: To determine the effect of transforming growth factor (TGF)-beta2 on the
pre-mRNA splicing pattern of fibronectin, as well as on the synthesis and
secretion of this glycoprotein by porcine trabecular cells. METHODS: First
passage porcine trabecular cells were rendered quiescent and incubated in culture
medium containing 15% newborn calf serum, in serum-free culture medium containing
either activated TGF-beta2 (concentration range: 0.2-2.7 ng/ml) or activated TGF
beta1 (1 ng/ml), or in serum-free medium alone (untreated control samples). For
investigation of alternative splicing, total RNA was extracted, and reverse
transcription-polymerase chain reaction (RT-PCR) was performed with primer pairs
located in exons flanking the exon (extra domain [ED]A, or EDB) that undergoes
alternative splicing. The polymerase chain reaction (PCR) products were verified
by Southern hybridization and quantified by using laser densitometry. The
percentage of EDA-positive (+) isoforms was compared with that of the EDB+
isoforms among the groups. To study the effect of TGF-beta2 on the synthesis and
secretion of fibronectin, total protein was extracted from both cultured cells
and conditioned medium, Western blot analysis was performed using an anti
fibronectin antibody, and the products were quantified by laser densitometry.
Immunocytochemical analysis was also performed on cultured trabecular cells to
detect fibronectin. RESULTS: Fibronectin mRNA that was detected in untreated
serum-starved control cells was EDA and EDB negative. Incubation of trabecular
cells in medium containing 1 ng/ml TGF-beta2, 1 ng/ml TGF-beta1, or 15% newborn
calf serum induced the expression of EDA+ and EDB+ mRNA to varying degrees. At
concentrations of 0.2, 0.5, 1.5, and 2.7 ng/ml, TGF-beta2 increased the
concentration of fibronectin by 2-, 3-, 3.8-, and 5-fold in the conditioned
medium, and by 3-, 3.7-, 4-, and 4.3-fold in the cell extracts, respectively. The
trabecular cells treated with TGF-beta2 exhibited strong immunoreaction for
fibronectin, whereas the cells incubated in serum-free medium showed only minimal
immunoreactivity. CONCLUSIONS: Our results demonstrate that TGF-beta2 and TGF
beta1 modified the alternative splicing pattern of fibronectin pre-mRNA and
enhanced the synthesis and secretion of this extracellular matrix molecule by
trabecular cells in a dose-dependent fashion. These findings indicate a mechanism
whereby TGF-beta2, the concentration of which is elevated in aqueous humor of
patients with primary open-angle glaucoma, contributes to the increased
deposition of extracellular matrix molecules in the outflow pathway.
PMID- 11006237
TI - Muller cell protection of rat retinal ganglion cells from glutamate and nitric
oxide neurotoxicity.
AB - PURPOSE: Low concentrations of excitotoxic agents such as glutamate and nitric
oxide decrease survival rates of purified retinal ganglion cells (RGCs). In the
retina, RGCs are ensheathed by retinal Muller glial (RMG) cell processes. The
purpose of this study was to determine whether RMG cells could protect RGCs from
these excitotoxic injuries. METHODS: RGCs were purified from 7- or 8-day-old Long
Evans rats and cultured on polylysine/laminin-coated coverslips in serum-free
medium for 2 days. The coverslips were then moved to dishes containing either
confluent RMG monolayers or no glial cells in glutamate-free medium. Some dishes
with confluent RMG cells were exposed to D,L-threo-beta-hydroxyaspartate (THA), a
blocker of glutamate uptake. Three days after exposure to various concentrations
of glutamate or the NO donor, 2, 2'-(hydroxynitroso-hydrazino)bisethanamine,
survival rates of RGCs were measured by calcein-acetoxymethyl ester staining.
Glutamate concentrations in the medium were measured using amino acid analysis.
RESULTS: Without RMG cells, the application of increasing concentrations (5-500
microM) of glutamate caused a dose-dependent increase in RGC death after 3 days.
The neurotoxic effects of glutamate were blocked in the RMG cell cocultures, even
when there was no direct contact between the cell types. The protective effect of
RMG cells was weakened by THA treatment. NO also had toxic effects on RGC. RMG
cells prevented this toxicity but only when in direct contact with the RGCs.
CONCLUSIONS: RMG cells can protect RGCs from glutamate and NO neurotoxicity. We
suggest that functional disorders of glutamate uptake in RMGs might be one of the
etiologies of glaucoma.
PMID- 11006238
TI - Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat
glaucoma model.
AB - PURPOSE: To characterize a long-term elevated intraocular pressure (IOP) glaucoma
model in the rat with respect to electroretinographic (ERG) changes and the
pattern and mechanism of retinal ganglion cell (RGC) death. METHODS; An
approximate doubling of IOP was induced in one eye (G) of female Wistar rats (150
180 g) by cautery of 3 episcleral/limbal veins. At intervals over 3 to 4 months,
measurements of IOP and ERG changes (contact-lens electrode) were made in both
the G and contralateral normal (N) eyes. At the end of 3 to 4 months of elevated
IOP, RGCs were fluorescently labeled with Fluorogold (retrogradely from the
superior colliculus), or retinas were labeled by intravitreal injection of a
mitochondrial potential indicator dye and stained for apoptotic nuclei with a DNA
dye. Flatmounts of fixed, dye-labeled retinas were examined by epifluorescence,
confocal, or interference contrast microscopy. RESULTS: Elevated IOP was
consistently maintained for up to 4 months in G eyes, but ERG a- and b-waves
showed a statistically significant decline, of 30% to 40% in amplitude, after 3
months. Loss of RGCs in G retinas was primarily focal with no statistically
significant loss demonstrable outside of the focal areas when assessed by an area
sampling method for counting RGCs, which totaled 2% to 3% of the entire retinal
area. Mitochondrial membrane potential of cells in the RGC layer was reduced by
17.5% (P: < 0.05) in regions surrounding areas of focal loss compared with
comparable locations in control N eyes. After 3.5 months' elevated IOP the G
retinas showed cell nuclei at various stages of apoptosis, from initial DNA
condensation to fragmentation. CONCLUSIONS: The three-vein episcleral/limbal vein
occlusion model for inducing glaucomatous pathology in the rat eye gives a
consistent long-term elevation of IOP. After 3 to 4 months of approximately 100%
increased IOP, the ERG responses begin to decline, there is a variable focal loss
of RGCs, and some of the remaining RGCs show characteristics of stress and
apoptosis. These changes seem consistent with retinal damage in human glaucoma
(focal field defects), and this rat model appears to mimic some features of
primary open-angle glaucoma.
PMID- 11006239
TI - Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute
IOP elevation in rats.
AB - PURPOSE: To determine whether acute experimental glaucoma in rats obstructs
retrograde transport of brain-derived neurotrophic factor (BDNF) to retinal
ganglion cells (RGCs). METHODS: Forty rats had unilateral injection of either
(125)I-BDNF (20 animals) or a mixture of (125)I-BDNF and 100-fold excess
nonradiolabeled BDNF (20 animals). In each group of 20 animals, eyes
contralateral to injection had either normal intraocular pressure (IOP; 10
animals) or IOP elevated to 25 mm Hg below the systolic blood pressure of the eye
(10 animals). In each group of 20 rats, ipsilateral eyes had IOP set at systolic
blood pressure (4 eyes), had optic nerve transection (10 eyes), or had normal IOP
(6 eyes). Six hours after injection, animals were killed and tissues were fixed,
embedded, and sectioned for autoradiography. Grain counts were performed over
retina and optic nerve using automated image analysis. RESULTS: IOP elevation to
25 mm Hg below systolic blood pressure (perfusion pressure [PP] 25) decreased
median retinal nerve fiber layer (NFL) grains by 38% compared with controls (P: <
0.001). Competition by cold BDNF reduced NFL grains by 28% (P: = 0.013).
Considering only the radioactivity representing specific retrograde transport of
BDNF, IOP elevation to PP25 reduced transport by 74%, whereas elevation to PP0
(equaling systolic blood pressure) reduced specific transport by 83%.
CONCLUSIONS: BDNF is transported retrogradely from the superior colliculus in
adult rats, and this transport is substantially inhibited by acute IOP elevation.
Deprivation of BDNF among RGCs may contribute to neuron loss in glaucoma.
PMID- 11006240
TI - Evidence that retinal pigment epithelium functions as an immune-privileged
tissue.
AB - PURPOSE: Tissues derived from immune-privileged sites sometimes possess special
characteristics that promote their own survival when transplanted to a
nonprivileged site. This study was undertaken to evaluate whether retinal pigment
epithelium (RPE) behaves as an immune-privileged tissue when transplanted
extraocularly. METHODS: RPE grafts were prepared from eyes of neonatal C57BL/6 or
C57BL/6 gld/gld (deficient in CD95 ligand expression) mice. These grafts (or
conjunctival grafts as positive controls) were transplanted into the anterior
chamber, the subretinal space, the subconjunctival space, and underneath the
kidney capsule of histoincompatible BALB/c mice. Transplant survival was
evaluated by histology at selected time points after engraftment. Recipients were
tested for acquisition of C57BL/6-specific delayed-type hypersensitivity (DH) and
for the ability to suppress DH. RESULTS: Allogeneic neonatal RPE grafts from
normal donors showed significantly enhanced survival at all graft sites compared
with conjunctival grafts. However, allogeneic RPE cell grafts from gld/gld mice
were rapidly rejected after transplantation beneath the kidney capsule.
Allogeneic RPE grafts placed in extraocular sites induced systemic DH directed at
donor alloantigens, whereas RPE allografts placed intraocularly induced
suppression of systemic DH. CONCLUSIONS: Allogeneic neonatal RPE grafts, through
constitutive expression of CD95 ligand, promote their own survival at heterotopic
sites. Paradoxically, these grafts also display immunogenicity. Thus, neonatal
RPE tissue owes its immune privilege to the capacity to prevent immune rejection
rather than to inhibit sensitization.
PMID- 11006241
TI - PCR-based evidence of bacterial involvement in eyes with suspected intraocular
infection.
AB - PURPOSE: To assess the usefulness of polymerase chain reaction (PCR) in detection
of bacteria in ocular samples. METHODS: Thirty-seven samples (aqueous and
vitreous) were collected from 25 eyes showing typical symptoms and clinical signs
of bacterial endophthalmitis. Ocular samples were also collected from 38 eyes
that underwent routine surgery and from 15 eyes with intraocular inflammation due
to nonbacterial causes. Panbacterial PCR was performed with a nested pair of 16S
rRNA gene primers. Subsequent bacterial identification was completed for 18
paired samples (nine eyes) using restriction fragment length polymorphism (RFLP)
and DNA sequencing. RESULTS: A 100% concordance was obtained between PCR and
culture-positive samples. A PCR product was amplified from all 37 intraocular
samples from eyes with suspected infection, whereas only 15 of 22 vitreous
samples and 5 of 15 aqueous samples were culture positive. Culture-negative PCR
positive samples contained a preponderance of gram-negative bacterial sequences.
Cloning and DNA analysis revealed 30 DNA sequences and included eight bacterial
16S rDNA, which currently remain unidentifiable. The presence of bacterial DNA
was associated with an inflammatory response suggestive of infection and not
colonization. All 15 samples from inflamed eyes with diverse uveitis diagnoses
were PCR negative. The false-positive rate, due to contamination during sampling,
was 5%. CONCLUSIONS: Bacterial DNA was detected in all patients with typical
clinical signs of endophthalmitis. Gram-negative organisms seem to play a much
more important role in the pathogenesis of this disease than previously thought.
PCR-based techniques have great value in the confirmation of the diagnosis of
bacterial endophthalmitis especially in culture-negative eyes.
PMID- 11006242
TI - Prospective determination of T-cell responses to S-antigen in Behcet's disease
patients and controls.
AB - PURPOSE: To prospectively determine, using two different assays, the lymphocyte
proliferative response to a retinal autoantigen (S-antigen) in patients with
Behcet's disease who are under treatment for ocular inflammation. METHODS:
Patients were evaluated at each visit for signs of ocular inflammation.
Peripheral blood leukocytes were harvested and cultured in the presence of bovine
S-antigen in a standard culture assay, as well as by limiting dilution using
multiple short-term T-cell lines. RESULTS: Five patients were observed for 2 to
10 months. During follow-up, three patients had episodes of ocular inflammation.
No consistent change in proliferative response was observed in standard
proliferation assays. However, an increase in established T-cell lines was
correlated to the presence of ocular inflammation in all three patients. Ocular
activity was associated with an increase of 9- to 30-fold in the frequency of
short-term T-cell lines. This increase returned to baseline within 1 to 3 months.
CONCLUSIONS: An increase in S-antigen-responsive lymphocytes is found in the
peripheral blood of patients with Behcet's disease during episodes of ocular
inflammation. This increase cannot be measured using standard proliferation
assays but requires the use of techniques exploiting the principles of limiting
dilution analysis.
PMID- 11006243
TI - Role and expression of CD40 on human retinal pigment epithelial cells.
AB - PURPOSE: To examine the CD40 costimulatory molecule expression on normal resting
or activated adult human retinal pigment epithelium (hRPE) cells and to evaluate
its role as an activation molecule considering the potential antigen presentation
functions of hRPE cells. METHODS: Expression of HLA-DR and costimulatory (CD40,
B7.1, B7.2, CD54, and CD58) molecules on hRPE cells was analyzed by flow
cytometry. CD40 triggering was performed using soluble CD40L or cocultures with
CD40L transfected fibroblasts. Interleukin (IL)-6, -8, -10, and -12 secretions
were measured by enzyme-linked immunosorbent assay. Antigen presentation function
of hRPE cells was assessed by coculturing hRPE cells with allogeneic T cells. T
cell proliferation was measured by [(3)H]-thymidine incorporation, and T-cell
apoptosis by measurement of caspase-3 activity. RESULTS: Interferon (IFN)gamma
activated hRPE cells expressed CD40, but not B7.1 or B7.2. Although
interferongamma enhanced IL-6 and IL-8 production, CD40 triggering of IFNgamma
activated hRPE cells did not induce IL-12 secretion. hRPE cells did not stimulate
allogeneic resting T cells and downregulated phytohemagglutinin-activated
allogeneic T cells via a cell-to-cell contact-dependent mechanism. Some induction
of apoptosis was detected. CONCLUSIONS: CD40 is expressed on IFNgamma-activated
hRPE cells. Its ligation leads to an increased production of IL-6 and IL-8 but
fails to induce B7.1 or B7. 2 expression, or to induce IL-12 secretion.
Accordingly, hRPE cells do not activate allogenic T cells but inhibit T-cell
proliferation, partly through induction of apoptosis. These results suggest that
hRPE cells could be implicated more in a deviant antigen presentation. If the
exact molecular mechanisms are unclear, it is likely that CD40-CD40L interaction
could play a role in this process.
PMID- 11006245
TI - Differential expression of N- and B-cadherin during lens development.
AB - PURPOSE: To analyze the dynamics of N- and B-cadherin cell adhesion molecule
expression and cytoskeletal interaction during embryonic chick lens development.
METHODS: Localization of N- and B-cadherin, F-actin, and connexin 56 were
determined by immunohistochemistry of developing lenses or immunocytochemistry of
differentiating primary lens cultures. Biochemical analysis of cytoskeletal
linkage of N- or B-cadherin was assessed by differential detergent extraction,
electrophoresis, and immunoblotting. RESULTS: The results indicate that although
both cadherins are expressed throughout lens development, N-cadherin expression
detected was similar in both lens epithelial and fiber cells, whereas B-cadherin
was preferentially localized to the lens fiber cells. During differentiation,
both cadherins become increasingly associated with the lens cytoskeleton, as
indicated biochemically by a transition from largely Triton X-100-soluble to
Triton X-100-insoluble pools and immunocytologically by cadherin localization to
cell-cell borders and colocalization with the actin cytoskeleton. Although a
significant fraction of N-cadherin remains Triton X-100-soluble as the lens cells
differentiate, B-cadherin becomes resistant to extraction by both Triton X-100 as
well as RIPA buffers. As detected immunocytochemically in lens cell cultures, the
temporal localization of N-cadherin to cell-cell interfaces precedes that of B
cadherin. Furthermore, temporal localization of B-cadherin, as opposed to N
cadherin, to cell-cell borders more closely parallels that of connexin 56 in
vitro as well as in vivo. CONCLUSIONS; These results suggest that while both N-
and B-cadherin are expressed during lens cell differentiation, both their
patterns of expression as well as their cytoskeletal association differ between
epithelial and fiber cells.
PMID- 11006244
TI - Chronic low level complement activation within the eye is controlled by
intraocular complement regulatory proteins.
AB - PURPOSE: To explore the role of the complement system and complement regulatory
proteins in an immune-privileged organ, the eye. METHODS: Eyes of normal Lewis
rats were analyzed for the expression of complement regulatory proteins, membrane
cofactor protein (MCP), decay-acceleration factor (DAF), membrane inhibitor of
reactive lysis (MIRL, CD59), and cell surface regulator of complement (Crry),
using immunohistochemistry, Western blot analysis, and reverse transcription
polymerase chain reaction (RT-PCR). Zymosan, a known activator of the alternative
pathway of complement system was injected into the anterior chamber of the eye of
Lewis rats. Animals were also injected intracamerally with 5 microl (25 microg)
of neutralizing monoclonal antibody (mAb) against rat Crry (5I2) or CD59 (6D1) in
an attempt to develop antibody induced anterior uveitis; control animals received
5 microl of sterile phosphate-buffered saline (PBS), OX-18 (25 microg), G-16
510E3 (25 microg), or MOPC-21 (25 microg). The role of complement system in
antibody-induced uveitis was explored by intraperitoneal injection of 35 U cobra
venom factor (CVF), 24 hours before antibody injection. Immunohistochemical
staining and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
with Western blot analysis were used to detect the presence of membrane attack
complex (MAC) and C3 activation products, respectively, in normal and antibody
injected rat eyes. RESULTS: Complement activation product MAC was present in the
normal rat eye, and intraocular injection of zymosan induced severe anterior
uveitis. The complement regulatory proteins, MCP, DAF, CD59, and Crry, were
identified in the normal rat eye. Soluble forms of Crry and CD59 were also
detected in normal rat aqueous humor. Severe anterior uveitis developed in Lewis
rats injected with a neutralizing mAb against Crry, with increased formation of
C3 split products. Systemic complement depletion by CVF prevented the induction
of anterior uveitis by anti-Crry mAb. Intracameral injection of anti-rat CD59
(6D1), anti-rat MHC class I antigen (OX-18), anti-rat Ig (G-16-510E3), or MOPC-21
caused no inflammatory reaction. CONCLUSIONS: The results suggest that the
complement system is continuously active at a low level in the normal eye and is
tightly regulated by intraocular complement regulatory proteins.
PMID- 11006246
TI - A nonsense mutation (W9X) in CRYAA causes autosomal recessive cataract in an
inbred Jewish Persian family.
AB - PURPOSE: To identify the genetic defect causing autosomal recessive cataract in
two inbred families. METHODS: Linkage analysis was performed with polymorphic
markers close to 14 loci previously shown to be involved in autosomal dominant
congenital cataract. In one of the families a gene segregating with the disease
was analyzed by single-strand conformation polymorphism (SSCP) and eventually
sequenced. RESULTS: Three polymorphic markers close to the CRYAA gene located on
chromosome 21q segregated with the disease phenotype in one of the families, but
not in the other. Sequencing of the CRYAA in this Jewish Persian family revealed
a G-to-A substitution, resulting in the formation of a premature stop codon
(W9X). CONCLUSIONS: A nonsense mutation in the CRYAA gene causes autosomal
recessive cataract in one family. This constitutes the first description of the
molecular defect underlying nonsyndromic autosomal recessive congenital cataract.
That there was no linkage to this locus in another family provides evidence for
genetic heterogeneity.
PMID- 11006247
TI - Effects of experimentally induced ametropia on the morphology and optical quality
of the avian crystalline lens.
AB - PURPOSE: To examine the effects of refractive error on avian lens morphology and
optical quality. METHODS: Hatchling white leghorn chicks were unilaterally
goggled for 7 days with either a form-deprivation goggle (n = 12), a -10 D
defocus goggle (n = 12), or a +10 D defocus goggle (n = 12) to induce myopia and
hyperopia. Optical quality of lenses (focal length and focal length variability)
from treated and contralateral control eyes was assessed using a scanning laser
apparatus. Lens morphology was examined by light and electron microscopy.
RESULTS: Although the induction of refractive errors did not significantly alter
lens size, shape, paraxial focal length, or average focal length, average focal
length variability increased. Lenses from eyes goggled with form-deprivation and
+10 D defocus goggles demonstrated a twofold increase in average focal length
variability, when compared with their contralateral controls. The morphology of
the lens is not altered by these experimental manipulations. CONCLUSIONS: This
study provides evidence that the refractive development of the chick lens is not
independent of the refractive development of the ocular globe and that chick
lenticular development is influenced by both genetics and visual experience.
PMID- 11006249
TI - Influence of exposure time for UV radiation-induced cataract.
AB - PURPOSE: It is believed that for a certain ultraviolet radiation (UVR) exposure,
the biologic effect depends on the product of irradiance and exposure time (the
reciprocity Bunsen-Roscoe law). The purpose of this study was to investigate the
validity of the reciprocity law for UVR-induced cataract. METHODS: Two
experiments were conducted. In the first one, 100 Sprague-Dawley rats were
exposed to UVR divided into five groups according to exposure time: 7.5, 15, 30,
60, and 120 minutes. In the second experiment, 80 Sprague-Dawley rats were
exposed to UVR divided into four groups according to exposure time: 5, 7.5, 11,
and 15 minutes. All the animals were unilaterally exposed to the same dose of UVR
(8 kJ/m(2)) in the 300-nm wavelength region. One week after exposure both lenses
were removed to measure the intensity of forward light scattering and for
microphotography. Groups were compared by evaluating the difference between
exposed and nonexposed eyes. RESULTS: The group exposed to UVR for 5 minutes had
the lowest intensity of forward light scattering. The highest intensity of
forward light scattering was found in the group that was exposed for 15 minutes.
With longer exposure intervals, the intensity of forward light scattering
decreased as the exposure time increased. No difference in intensity of forward
light scattering was found between the groups exposed for 60 and 120 minutes.
CONCLUSIONS; Exposure time strongly influenced cataract formation after low-dose
UVR. In this model of UVR-induced cataract, the photochemical reciprocity law was
modulated by a biologic response.
PMID- 11006248
TI - DeltaFosB-induced cataract.
AB - PURPOSE: The objective of this study was to investigate a possible relationship
between posterior subcapsular cataract (PSC) formation and expression of the
transcription factor DeltaFosB. METHODS: Western blot analysis was performed on
bitransgenic NSE-tTA, TetOp-DeltaFosB, and single-transgenic NSE-tTA control mice
to determine the pattern of DeltaFosB expression within the eye. Light and
scanning electron microscopy and biochemical analyses were also performed.
RESULTS: In mice expressing DeltaFosB, cataract developed that initially appeared
to be posterior subcapsular and gradually matured to involve the entire lens. The
enlarged posterior ends of developing secondary fibers curved away from the
visual axis to form an elevated opaque posterior plaque. As a result, posterior
suture formation did not occur. At a later time, the attenuated posterior capsule
overlying the plaque ruptured and the lens nucleus subluxated into the vitreous.
Retinal damage was also observed but only from postnatal day 65, a time when
extensive lens degeneration had already occurred. DeltaFosB expression was
observed well before the detection of morphologic change in both the lens and the
retina. Within the lens, DeltaFosB expression was found in both the epithelium
and fibers. The development of cataracts was a direct consequence of DeltaFosB
expression and was not due to the disruption of an endogenous gene by transgene
integration since cataracts could be prevented by silencing expression of
DeltaFosB by feeding bitransgenic animals doxycycline (Dox). Moreover, cataracts
were observed in bitransgenic mice derived from two independent TetOp-DeltaFosB
founder lines but not in single NSE-tTA transgenic controls. Cataractogenesis was
not a consequence of abnormal development, because mice conceived and raised on
Dox to prevent expression of DeltaFosB also were subject to formation of PSC when
expression of DeltaFosB was turned on in adult animals by removing Dox.
Examination of biochemical parameters indicated that the earliest change observed
was the disruption of calcium homeostasis with a significant increase in Ca(2+)
influx, followed by a gradual but marked decrease in protein content. Significant
changes in certain metabolic parameters and protein composition were also
observed. CONCLUSIONS: The DeltaFosB-induced cataract in which the major
morphologic early event was the disruption of normal posterior fiber formation,
may be a good model for PSC. By identifying DeltaFosB-regulated target genes, it
should be possible to achieve a better understanding of the molecular mechanisms
through which PSC is formed.
PMID- 11006250
TI - Susceptibility to TGFbeta2-induced cataract increases with aging in the rat.
AB - PURPOSE: Cataract is the most common cause of blindness in the world today, and
yet there is no generally accepted treatment other than surgical intervention.
Studies in rodent models designed to increase understanding of the molecular
basis of cataract have shown that transforming growth factor (TGF)-beta induces
morphologic and molecular changes similar to those associated with some forms of
human cataract. Because aging is the most widely recognized risk factor for
cataract, it is important that any animal model be examined in this context. This
was a study of the effects of aging on susceptibility to TGFbeta-induced
cataract. METHODS: Lenses from weanling, adult, and senile rats were cultured in
defined serum-free medium with a range of concentrations of TGFbeta2. The lenses
were cultured for up to 7 days, photographed daily, fixed, and prepared for
histology and immunolocalization. Opacification was quantified by image analysis.
RESULTS: Lenses from weanling, adult, and senile rats all underwent similar
cataractous changes when exposed to TGFbeta. This included opacification, the
formation of anterior subcapsular plaques, and accumulation of type I collagen
and alpha-smooth muscle actin. Lenses from adult and senile animals, however,
were generally more adversely affected by TGFbeta than lenses from weanlings.
This study also showed that a low dose of TGFbeta administered over a prolonged
period had an effect similar to that of a higher dose administered over a shorter
period. CONCLUSIONS: An elevation of TGFbeta activity, either acute or chronic,
and/or an age-related increase in lens cell susceptibility to TGFbeta may be
triggering factors in the etiology of certain forms of cataract.
PMID- 11006251
TI - Methazolamide 1% in cyclodextrin solution lowers IOP in human ocular
hypertension.
AB - PURPOSE: To formulate aqueous eye drops containing methazolamide 1% in
cyclodextrin solution and to evaluate their effect on intraocular pressure (IOP)
in a double-blind randomized trial in humans. Methazolamide, a carbonic anhydrase
inhibitor (CAI), has been used in oral doses in the treatment of glaucoma but
hitherto has not been successfully formulated in eye drops. In this study the
effects of methazolamide are compared with those of dorzolamide (Trusopt).
METHODS: Methazolamide 1% was formulated in a 2-hydroxypropyl-beta-cyclodextrin
with hydroxypropyl methylcellulose in aqueous solution. Eight persons with ocular
hypertension were treated with the methazolamide-cyclodextrin eye drops and eight
persons with dorzolamide (Trusopt), both groups at dosages of three times a day
for 1 week. IOP was measured before treatment was begun and on days 1, 3, and 8
at 9 AM (peak) and 3 PM (trough). RESULTS: After 1 week of treatment, the peak
IOP in the methazolamide group had decreased from 24.4 +/- 2.1 mm Hg (mean +/-
SD) to 21.0 +/- 2.0 mm Hg, which is a 14% pressure decrease (P: = 0.006). In the
dorzolamide group, the peak IOP decreased from 23.3 +/- 2.1 mm Hg to 17.2 +/- 3.1
mm Hg, which is a 26% pressure decrease (P: < 0.001). On average, the IOP
declined 3.4 +/- 1.8 mm Hg after methazolamide administration and 6.1 +/- 3.6 mm
Hg after dorzolamide. CONCLUSIONS: Through cyclodextrin complexation, it is
possible to produce topically active methazolamide eye drops that lower IOP. This
is the first double-blind clinical trial that demonstrates the efficacy of the
classic CAIs in eye drop formulation.
PMID- 11006252
TI - A retinal-derived relaxing factor mediates the hypoxic vasodilation of retinal
arteries.
AB - PURPOSE: To investigate the mechanisms involved in hypoxic vasodilation using an
in vitro setup. METHODS: Retinal arteries with and without retinal tissue were
mounted on a wire myograph. The segments were contracted with prostaglandin
(PG)F(2alpha) (30 microM) or 120 mM K(+). Hypoxia was induced by replacement of
O(2) by N(2) in the gas used to bubble the Krebs-Ringer bicarbonate organ bath
solution. RESULTS: Hypoxia induced complete relaxation of preparations with
adherent retinal tissue contracted with PGF(2alpha). Preparations without retinal
tissue were not affected by the change in oxygenation. When the retinal arteries
were contracted with 120 mM K(+), hypoxia no longer induced relaxation of the
preparation with adherent retinal tissue. The presence of an NO-synthase
inhibitor (L-NA, 0.1 mM), a cyclooxygenase inhibitor (indomethacin, 50 microM),
or an adenosine receptor antagonist (8-sulfophenyltheophylline, 1 mM) did not
affect hypoxic vasodilation. Excitatory amino acids and lactate had no or only a
limited effect on the PGF(2alpha)-induced contraction and are therefore unlikely
mediators of hypoxic vasodilation. HCl (10 mM) reduced the pH to 6.1 +/- 0.08 (n
= 4) and induced a pronounced but transient relaxation of the retinal artery
contracted with PGF(2alpha) or 120 mM K(+), whereas hypoxia induced relaxation of
the retinal artery contracted with PGF(2alpha) only in the presence of adherent
retinal tissue. CONCLUSIONS: Adherent retinal tissue mediates the hypoxic
vasodilatation of bovine retinal arteries in vitro. Neither NO, prostanoids,
adenosine, excitatory amino acids lactate or changes in pH seem to be involved in
this hypoxic response.
PMID- 11006253
TI - Altered expression of retinal occludin and glial fibrillary acidic protein in
experimental diabetes. The Penn State Retina Research Group.
AB - PURPOSE: To investigate how diabetes alters vascular endothelial cell tight
junction protein and glial cell morphology at the blood-retinal barrier (BRB).
METHODS: The distribution of the glial marker, glial fibrillary acidic protein
(GFAP), and the endothelial cell tight junction protein occludin were explored by
immunofluorescence histochemistry in flatmounted retinas of streptozotocin (STZ)
diabetic and age-matched control rats, and in BB/Wor diabetes-prone and age
matched diabetes-resistant rats. RESULTS: GFAP immunoreactivity was limited to
astrocytes in control retinas. Two months of STZ-diabetes reduced GFAP
immunoreactivity in astrocytes and increased GFAP immunoreactivity in small
groups of Muller cells. After 4 months of STZ-induced diabetes, all Muller cells
had intense GFAP immunoreactivity, whereas there was virtually none in the
astrocytes. BB/Wor diabetic rats had similar changes in GFAP immunoreactivity.
Occludin immunoreactivity in normal rats was greatest in the capillary bed of the
outer plexiform layer and arterioles of the inner retina but much less intense in
the postcapillary venules. Diabetes reduced occludin immunoreactivity in the
capillaries and induced redistribution from continuous cell border to
interrupted, punctate immunoreactivity in the arterioles. Forty-eight hours of
insulin treatment reversed the pattern of GFAP and occludin immunoreactivity in
the STZ-diabetic rats. CONCLUSIONS: Diabetes alters GFAP expression in retinal
glial cells, accompanied by reduction and redistribution of occludin in
endothelial cells. These changes are consistent with the concept that altered
glial-endothelial cell interactions at the BRB contribute to diabetic
retinopathy.
PMID- 11006254
TI - Safety and pharmacokinetics of an intraocular fluocinolone acetonide sustained
delivery device.
AB - PURPOSE: To determine the safety and pharmacokinetics of an intraocular
fluocinolone acetonide sustained drug delivery device. METHODS: Nonbiodegradable
drug delivery devices containing 2 or 15 mg of a synthetic corticosteroid,
fluocinolone acetonide, were constructed. The long-term in vitro release rates of
these devices were determined in protein-free buffer or buffer containing 50%
plasma protein. Fifteen-milligram devices were also implanted into the vitreous
cavities of rabbit eyes. Intravitreal drug levels, the amount of drug remaining
in explanted devices, and the release rate of explanted devices were determined
over a 1-year time period. Drug toxicity was assessed over this same time period
by slit lamp examination, indirect ophthalmoscopy, electroretinography, and
histologic examination. RESULTS: The drug release rates for the 2-mg device, 1.9
+/- 0.25 microg/d, and for the 15-mg device, 2.2 +/- 0.6 microg/d, remained
linear over the 6-month and 45-day testing period, respectively. The release rate
increased by approximately 20% when devices were transferred from protein-free
buffer to buffer that contained protein (P: < 0.0001). Vitreous levels remained
fairly constant (0.10-0.21 microg/ml) over a 1-year period. No drug was present
in the aqueous humor during this time period. Based on the device release rates,
the predicted life span of the 2- and 15-mg devices are 2.7 and 18.6 years,
respectively. There was no evidence of drug toxicity by clinical examination,
electroretinography, or histologic examination. CONCLUSIONS: It is feasible to
construct a nontoxic fluocinolone acetonide drug delivery device that
reproducibly releases fluocinolone acetonide in a linear manner over an extended
period. These devices show great promise in the treatment of ocular diseases such
as uveitis, which are often managed with chronic corticosteroid therapy.
PMID- 11006255
TI - Elevation of vitreous leptin in diabetic retinopathy and retinal detachment.
AB - PURPOSE: Leptin is a cytokine that regulates energy metabolism and is linked to
diabetes mellitus through its metabolic actions. Leptin is angiogenic and
promotes wound healing, and therefore this investigation was conducted to
determine whether leptin is associated with neovascular and fibrotic
complications of diabetes and other retinopathies. METHODS: Serum and vitreous
samples were collected from patients classified by the presence and type of
diabetic retinopathy or other ocular diseases. Leptin was measured in serum and
vitreous by radioimmunoassay, and leptin and leptin receptor were localized in
epiretinal membranes immunohistochemically. RESULTS: Leptin levels in serum and
vitreous were higher in patients with diabetes than in those without, and
vitreous leptin concentrations were especially elevated in patients with
proliferative diabetic retinopathy or retinal detachment. Leptin and leptin
receptor were detected in fibrovascular epiretinal membrane of patients with
diabetes. CONCLUSIONS: Leptin in human vitreous is elevated in proliferative
diabetic retinopathy, and retinal detachment and is present in fibrovascular
epiretinal tissue. These data suggest an involvement of leptin in retinal
disease.
PMID- 11006256
TI - Choroidal neovascularization in the rat induced by adenovirus mediated expression
of vascular endothelial growth factor.
AB - PURPOSE: To determine the effects of an adenovirus vector encoding vascular
endothelial growth factor(165) (Ad.VEGF) delivered to the subretinal space in the
rat. METHODS: An E1-deleted adenoviral vector encoding VEGF was injected into the
subretinal space of Long-Evans rats. Immunohistochemistry identified VEGF
expression. Histopathologic changes in the retina were determined by light and
electron microscopy, immunohistochemistry, fluorescein angiography, and
examination of wholemounts of choroid and retina. RESULTS: Increased expression
of VEGF only in the retinal pigment epithelium (RPE) was detected after Ad.VEGF
injection. Histopathology of these eyes revealed minimal subretinal exudation at
1 week followed by the appearance of vascular structures in the subretinal space
by week 2, which persisted up to 4 weeks. Shortening of photoreceptor outer
segments and reduction of the outer nuclear layer were present overlying areas of
neovascularization. Fluorescein angiography of animals injected with fluorescein
dextran revealed a deep complex of new vessels. Choroidal flatmounts showed new
vessel formation, verified by detection of endothelial cells via
immunohistochemistry, arising from the choroid with absence of change in the
overlying retinal vasculature. Electron microscopy confirmed the presence of sub
RPE endothelial cells and pericytes and the loss of integrity of Bruch's
membrane, and serial sectioning demonstrated choroidal vascular growth through
Bruch's membrane. CONCLUSIONS: These results support the hypothesis that
overexpression of VEGF from RPE cells is capable of inducing choroidal
neovascularization in the rat and provide a framework for further examining
angiogenic processes in the RPE-choroid complex.
PMID- 11006257
TI - Coordination between production and turnover of interphotoreceptor retinoid
binding protein in zebrafish.
AB - PURPOSE: Interphotoreceptor retinoid-binding protein (IRBP), which is secreted by
the photoreceptors of most vertebrates, is the major soluble protein component of
the interphotoreceptor matrix (IPM). Recent studies suggest that IRBP is short
lived in the IPM (half-life, approximately 11 hours). The mechanisms coordinating
the production and removal of IRBP are not known. Zebrafish provide a useful
system to study the regulation of these two processes, because its IRBP mRNA
levels are under circadian regulation. In the present study, the relationship
between the quantity of IRBP, the rate of its turnover, and the expression of its
mRNA in the zebrafish retina were examined. METHODS: Full-length zebrafish IRBP
was expressed in Escherichia coli and an antiserum generated against purified
recombinant IRBP. Western and protein dot blot analyses and indirect
immunofluorescence were used to define the temporal and spatial patterns of IRBP
expression in the adult zebrafish. In vivo and in vitro metabolic labeling
experiments were used to examine the regulation of IRBP turnover by both
environmental light and the light-dark cycle. RESULTS: Despite the known
rhythmicity in IRBP mRNA expression, neither the amount of IRBP nor its
localization changes significantly during the light-dark cycle. IRBP is rapidly
removed from the zebrafish eye (half life, approximately 7 hours). This rapid
turnover is independent of environmental lighting conditions during subjective
day and is more rapid during the day than at night. CONCLUSIONS: Because the
amount of IRBP remains constant throughout the day, the enhanced daytime IRBP
mRNA expression may function to compensate for an increased turnover of the
protein during the day. These findings suggest that the processes of IRBP
production and removal are coordinately regulated.
PMID- 11006258
TI - Distribution and developmental regulation of AMPA receptor subunit proteins in
rat retina.
AB - PURPOSE: To learn more about a possible functional role of alpha-amino-3-hydroxy
5-methyl-4-isoxasole-propionate (AMPA) receptors in retinal development, the
spatial distribution and temporal regulation of all AMPA receptor subunit
proteins was studied in rats. METHODS: Immunohistochemistry was performed on
retinal sections between embryonic days (E)20 and E21 and the adult stage by
using specific antibodies against AMPA subunits GluR1 to 4. RESULTS: All AMPA
subunits were expressed in the ganglion cell layer from E21 on. In the inner
plexiform layer (IPL), discernible bands of labeling appeared at distinct retinal
ages for the different subunits. GluR1 immunoreactivity (IR) was concentrated in
two broad bands by postnatal day (P)3, whereas three bands were visible beginning
on P9. Two bands were located in a region of the IPL where off-cells terminate,
and one band was found in the innermost part of the IPL where on-cells terminate.
In contrast, two bands of GluR2/3- and GluR4-IR in the IPL were only discernible
beginning on P14 and seemed to be located between the bands of GluR1-IR. GluR2/3
and GluR4 were observed both in horizontal cells and in the outer plexiform layer
from early developmental stages on. GluR1 was not found in the outer retina,
indicating that horizontal and bipolar cell processes in the rat express AMPA
receptors composed of subunits GluR2 to 4. Double-labeling experiments with cell
specific markers revealed the expression of subunits GluR1 to 4 in cholinergic
and AII amacrine cells. CONCLUSIONS: AMPA receptors are expressed before synapse
formation, indicating a role not only in fast signal transmission but also in the
establishment of inner retinal circuits. The differences in spatial and temporal
subunit expression suggest that different retinal cell types selectively express
distinct types of AMPA receptors during development of the rat retina.
PMID- 11006259
TI - Lipid peroxidation and peroxynitrite in retinal ischemia-reperfusion injury.
AB - PURPOSE: To investigate whether lipid peroxides play a role in retinal cell death
due to ischemia-reperfusion injury, whether recombinant human thioredoxin (rhTRX)
treatment reduces production of lipid peroxides of the retina, and whether such
treatment reduces the number of cells expressing c-Jun and cyclin D1. METHODS:
Retinal ischemia was induced in rats by increasing the intraocular pressure to
110 mm Hg for 60 minutes. After reperfusion, immunohistochemical staining for
lipid peroxide, peroxynitrite, c-Jun, and cyclin D1 and propidium iodide (PI)
staining were performed on retinal sections from animals treated intravenously
with and without rhTRX, a free radical scavenger. Quantitative analyses of PI-, c
Jun-, and cyclin D1-positive cells were performed after the ischemic insult.
Concentration of lipid peroxides in the retina was determined by the
thiobarbituric acid assay. RESULTS: Specific immunostaining for lipid peroxides
was seen in the ganglion cell layer at 6 hours after reperfusion, in the inner
nuclear layer at 12 hours, and in the outer nuclear layer at 48 hours. Time
course studies for PI-positive cells in the three nuclear layers coincided with
those of specific immunostaining for lipid peroxides. The specific immunostaining
was weakened by pre- and posttreatment with 0.5 mg of rhTRX. The number of PI-, c
Jun-, and cyclin D1-positive cells and the concentration of lipid peroxides were
significantly decreased by treatment with rhTRX compared with those of vehicle
treated control rats (P: < 0. 01). CONCLUSIONS: Lipid peroxides formed by free
radicals may play a role in neuronal cell death in retinal ischemia-reperfusion
injury.
PMID- 11006261
TI - Retinal degeneration is slowed in transgenic rats by AAV-mediated delivery of FGF
2.
AB - PURPOSE: We evaluated adeno-associated virus (AAV)-mediated gene transfer of
basic fibroblast growth factor (FGF-2) as a therapy for photoreceptor
degeneration in a transgenic rat model of retinitis pigmentosa. METHODS:
Recombinant adeno-associated virus vector (rAAV) incorporating a constitutive
cytomegalovirus (CMV) promoter was used to transfer the bovine FGF-2 gene to
photoreceptors. AAV was administered by subretinal injection to transgenic rats
(TgN S334ter-4) at postnatal day 15 (P15). Control eyes were uninjected, injected
with PBS, or AAV-LacZ. Eyes were examined by histopathology, morphometric
analysis, and electroretinography at P60. RESULTS: Expression of recombinant FGF
2 slowed the rate of photoreceptor degeneration. Morphologic studies demonstrated
significantly more photoreceptors surviving in eyes injected with AAV-FGF-2 than
in controls. Insignificant rescue effects were seen in retinas injected with
buffer only. No significant inflammatory response or neovascularization was
detected. Electroretinographic (ERG) responses of eyes injected with AAV-FGF-2
were increased compared with uninjected eyes; however, these amplitudes were not
significantly larger than eyes receiving an AAV-LacZ control vector. CONCLUSIONS:
Transduction of retinal cells with AAV-FGF-2 reduces the rate of photoreceptor
degeneration in an S334ter-4 animal model. Despite the lack of significantly
increased ERG amplitudes from eyes expressing FGF-2, a greater number of
surviving photoreceptors was demonstrated. Delivery of FGF-2 using recombinant
AAV has potential as a therapy for retinal degeneration.
PMID- 11006260
TI - Depression of retinal glutamate transporter function leads to elevated
intravitreal glutamate levels and ganglion cell death.
AB - PURPOSE: Elevated levels of extracellular glutamate have been implicated in the
pathophysiology of neuronal loss in both central nervous system and ophthalmic
disorders, including glaucoma. This increase in glutamate may result from a
failure of glutamate transporters (molecules that ordinarily regulate
extracellular glutamate; E:xcitatory A:mino A:cid T:ransporter; EAAT). Elevated
glutamate levels can also lead to alterations in glutamate receptor expression.
It was hypothesized that selective blockade of glutamate transporters would be
toxic to retinal ganglion cells. METHODS: Glutamate transporters were blocked
either pharmacologically or with subtype-specific antisense oligonucleotides
against EAAT1. Glutamate levels, transporter levels and ganglion cell survival
were assayed. RESULTS: Pharmacological inhibition of glutamate transporters with
either an EAAT2 specific inhibitor or a nonspecific inhibitor of all the subtypes
of transporters was toxic to ganglion cells. Treatment with oligonucleotides
against the glutamate transporter EAAT1 decreased the levels of expression of the
transporter, increased vitreal glutamate, and was toxic to ganglion cells.
CONCLUSIONS: These results demonstrate that normal function of EAAT1 and EAAT2 is
necessary for retinal ganglion cell survival and plays an important role in
retinal excitotoxicity. Manipulation of retinal glutamate transporter expression
may become a useful tool in understanding retinal neuronal loss.
PMID- 11006262
TI - Effects of hypoxemia on the a- and b-waves of the electroretinogram in the cat
retina.
AB - PURPOSE: Slow components of the electroretinogram (ERG) are sensitive to even
mild hypoxemia (60 < P(a)O(2) < 100 mm Hg) in the cat eye. However, the
electrical responses of the inner retina remain unchanged until P(a)O(2) is below
40 mm Hg. In this study, the effects of hypoxemia on photoreceptors, on which
both slow ERG components and inner retinal activity depend, were examined by
recording the a-wave of the ERG. METHODS: The ERG of dark-adapted, anesthetized
cats was recorded between an Ag-AgCl electrode in the vitreous humor and a
reference electrode near the eye. Responses to bright flashes of diffuse white
light were recorded at 3-minute intervals during hypoxemic episodes lasting 15
minutes to 2 hours. RESULTS: The cat a-wave was well described by the Lamb and
Pugh a-wave model during normoxia and hypoxemia. During mild hypoxemia (P(a)O(2)
of 50-60 mm Hg), small changes in a-wave amplitude were detected but did not
become greater during severe hypoxemia. The mean decrease in the a-wave amplitude
during severe hypoxemia (P(a)O(2) of 20-30 mm Hg) was 8.9% from the mean
amplitude during air breathing. The effects of hypoxemia were more severe on the
b-wave amplitude. The mean decrease in the b-wave was 35% at P(a)O(2) of 20-30 mm
Hg. CONCLUSIONS: The a-wave is more resistant to severe hypoxemia than the b
wave. This implies that photoreceptor transduction works almost normally during
hypoxemia and that failure of inner retinal PO(2) regulation causes the decrease
in the b-wave. Previously observed changes in the amplitudes of slow ERG
components during hypoxemia may result from changes in the ionic environment,
rather than a failure of photoreceptor energy metabolism.
PMID- 11006263
TI - The nature and extent of retinal dysfunction associated with diabetic macular
edema.
AB - PURPOSE: To evaluate the nature and extent of retinal dysfunction in the macular
and surrounding areas that occurs in patients with diabetes with clinically
significant macular edema (CSME). METHODS: Eleven patients were evaluated before
focal laser treatment. Multifocal electroretinogram (ERG) and full-field ERG
techniques were used to assess the effects of diabetic retinopathy and CSME on
macular, paramacular, and peripheral retinal function. A modified visual field
technique was used to obtain local threshold fields. The relationship between
local sensitivity changes and local ERG changes was determined. RESULTS: Local
ERG responses were significantly delayed and decreased in amplitude, and timing
changes were observed in a larger area of the retina than amplitude changes.
Visual field deficits were similarly widespread with marked sensitivity losses
occurring in retinal areas with normal ERG amplitudes and in areas that appeared
to be free of fundus abnormalities. Despite this similarity and the finding that
retinal areas with elevated thresholds have timing delays, timing delays were not
good predictors of the degree of threshold elevation. CONCLUSIONS: The results
demonstrate the widespread nature of timing deficits and visual field deficits
that are associated with CSME.
PMID- 11006265
TI - Defining ocular diseases
PMID- 11006264
TI - Retinal function in diabetic macular edema after focal laser photocoagulation.
AB - PURPOSE: To assess the effects of focal photocoagulation on retinal function in
the macular and perimacular areas in patients with diabetes who have clinically
significant macular edema. METHODS: Eleven patients were assessed after focal
laser treatment. Multifocal electroretinogram (ERG) and full-field ERG techniques
were used to evaluate the effects of treatment on macular, paramacular, and
peripheral retinal function. A modified visual field technique was used to obtain
local threshold fields. The posttreatment results were compared with pretreatment
results. Changes in local ERG response amplitudes and implicit times were
calculated for each patient and presented as difference fields. The changes in
local ERG responses were compared with the changes in local field sensitivity.
RESULTS: After treatment, the results of the psychophysical tests suggested
little or no change in visual function, but changes in retinal function were
observed with the multifocal ERG technique. Local ERG responses showed increases
in implicit time and decreases in amplitude, compared with pretreatment values.
Timing was affected more than amplitude. CONCLUSIONS: The results suggest that
focal treatment produces changes in retinal function, and these changes are not
restricted to the treated macular area.
PMID- 11006266
TI - XIST RNA associates with specific regions of the inactive X chromatin.
AB - Microscopy studies have shown that XIST RNA colocalizes with the inactive X
chromosome (Xi). However, the molecular basis for this colocalization is unknown.
Here we provide two lines of evidence from chromatin immunoprecipitation
experiments that XIST RNA physically associates with the Xi chromatin. First,
XIST RNA can be co-precipitated by antiserum against macroH2A, a histone H2A
variant enriched in the Xi. Second, XIST RNA can be co-precipitated by antisera
that recognize unacetylated, but not acetylated, isoforms of histones H3 and H4.
The specificity of XIST RNA association with hypoacetylated chromatin, together
with the previous finding that hypoacetylated histone H4 is enriched at promoters
of X-inactivated genes, raises the possibility that XIST RNA may contribute to
the hypoacetylation of specific regions of the Xi so as to alter the expression
of X-linked genes.
PMID- 11006267
TI - Chemical rescue of a mutant protein-tyrosine kinase.
AB - Protein-tyrosine kinases contain a catalytic loop Arg residue located either two
or four positions downstream of a highly conserved Asp residue. In this study,
the role of this Arg (Arg-318) in the protein-tyrosine kinase C-terminal Src
kinase (Csk) was investigated. The observed k(cat) for phosphorylation of the
random copolymer poly(Glu,Tyr) substrate by Csk R318A is approximately 3000-fold
smaller compared with that of wild type Csk, whereas the K(m) values for ATP and
poly(Glu,Tyr) are only mildly affected. The k(cat) value for poly(Glu,Tyr)
phosphorylation by the Csk double mutant A316R,R318A is 100-fold greater than the
k(cat) value for the single R318A mutant, suggesting that an Arg positioned at
the alternative location fulfills a similar function as in wild type. Csk R318A
kinase activity can also be partially recovered by several exogenous small
molecules including guanidinium and imidazole. These molecules contain key
features whose roles in catalysis can be rationalized from a known x-ray
structure of the insulin receptor tyrosine kinase. Imidazole is the best of these
activators, enhancing phosphorylation rates by Csk R318A up to 100-fold for
poly(Glu,Tyr) and significantly stimulating Csk R318A phosphorylation of the
physiologic substrate Src. This chemical rescue of mutant protein kinase activity
might find applications in cell signal transduction experiments.
PMID- 11006268
TI - Thyroid-stimulating hormone and cyclic AMP activate p38 mitogen-activated protein
kinase cascade. Involvement of protein kinase A, rac1, and reactive oxygen
species.
AB - p38 mitogen-activated protein kinases (p38-MAPKs) are activated by cytokines,
cellular stresses, growth factors, and hormones. We show here that p38-MAPKs are
activated upon stimulation by thyroid-stimulating hormone (TSH) or cAMP. TSH
caused the phosphorylation of p38-MAPK in Chinese hamster ovary cells stably
transfected with the human TSH receptor but not in wild-type Chinese hamster
ovary cells. The effect of TSH was fully mimicked by the adenylyl cyclase
activator, forskolin, and by a permeant analog of cAMP. The effect of forskolin
was reproduced in FRTL5 rat thyroid cells. TSH also stimulated the
phosphorylation of MAPK kinase 3 or 6, over the same time scale as that of p38
MAPKs. TSH and forskolin stimulated the activity of the alpha-isoform of p38-MAPK
assayed by phosphorylation of the transcription factor ATF2. The activity of MAPK
activated protein kinase-2 was stimulated by TSH and forskolin. This stimulation
was abolished by SB203580, a specific inhibitor of p38-MAPKs. The protein kinase
A inhibitor H89 inhibited the stimulation of phosphorylation of p38-MAPKs by
forskolin, whereas inhibitors of protein kinase C, p70(S6k), and
phosphatidylinositol 3-kinase were ineffective. Expression of the dominant
negative form of Rac1, but not that of Ras, blocked forskolin-induced p38-MAPK
activation. Diphenylene iodonium, a potent inhibitor of NADPH oxidase(s), and
ascorbic acid, an effective free radical scavenger, suppressed TSH- or forskolin
stimulated p38-MAPK phosphorylation, indicating that the generation of reactive
oxygen species plays a key role in signaling from cAMP to p38-MAPKs. Inhibition
of the p38-MAPK pathway with SB203580 partially but significantly, attenuates
cAMP- and TSH-induced expression of the sodium iodide symporter in FRTL-5 cells.
These results point to a new signaling pathway for the G(s)-coupled TSH receptor,
involving cAMP, protein kinase A, Rac1, and reactive oxygen species and resulting
in the activation of a signaling kinase cascade that includes MAPK kinase 3 or 6,
p38-MAPK, and MAPK-activated protein kinase-2.
PMID- 11006269
TI - Regions of prostate-specific antigen (PSA) promoter confer androgen-independent
expression of PSA in prostate cancer cells.
AB - Prostate-specific antigen (PSA) is expressed primarily by both normal prostate
epithelium and the vast majority of prostate cancers. Increases in serum PSA
during endocrine therapy are generally considered as evidence for prostate cancer
recurrence or progression to androgen independence. The mechanisms by which PSA
up-regulation occurs in androgen-refractory prostate cancer cells are unknown. In
this study, by using LNCaP and its lineage-derived androgen-independent PSA
producing subline, C4-2, we identified two cis-elements within the 5.8-kilobase
pair PSA promoter that are essential for the androgen-independent activity of PSA
promoter in prostate cancer cells. First, a previously reported 440-bp androgen
responsive element enhancer core (AREc) was found to be important for the high
basal PSA promoter activity in C4-2 cells. Both mutation analysis and supershift
experiments demonstrated that androgen receptor (AR) binds to the AREs within the
AREc and activate the basal PSA promoter activity in C4-2 cells under androgen
deprived conditions. Second, a 150-bp pN/H region was demonstrated to be a strong
AR-independent positive-regulatory element of the PSA promoter in both LNCaP and
C4-2 cells. Through DNase I footprinting and linker scan mutagenesis, a 17-bp RI
site was identified as the key cis-element within the pN/H region. Data from
electrophoretic mobility shift analysis and UV cross-linking experiments further
indicated that a 45-kDa (p45) cell-specific transcription factor associates with
RI in prostate cancer cells and may be responsible for driving the PSA promoter
activity independent of androgen and AR. Furthermore, by juxtaposing AREc and
pN/H, we produced a chimeric PSA promoter (supra-PSA) that exhibits 2-3-fold
higher activity than the wild type PSA promoter in both LNCaP and C4-2 cells.
PMID- 11006270
TI - A mutant Escherichia coli tyrosyl-tRNA synthetase utilizes the unnatural amino
acid azatyrosine more efficiently than tyrosine.
AB - Alloproteins, proteins that contain unnatural amino acids, have immense potential
in biotechnology and medicine. Although various approaches for alloprotein
production exist, there is no satisfactory method to produce large quantities of
alloproteins containing unnatural amino acids in specific positions. The tyrosine
analogue azatyrosine, l-beta-(5-hydroxy-2-pyridyl)-alanine, can convert the ras
transformed phenotype to normal phenotype, presumably by its incorporation into
cellular proteins. This provided the stimulus for isolation of a mutant tyrosyl
tRNA synthetase (TyrRS) capable of charging azatyrosine to tRNA. A plasmid
library of randomly mutated Escherichia coli tyrS (encoding TyrRS) was made by
polymerase chain reaction techniques. The desired TyrRS mutants were selected by
screening for in vivo azatyrosine incorporation of E. coli cells transformed with
the mutant tyrS plasmids. One of the clones thus isolated, R-6-A-7, showed a 17
fold higher in vivo activity for azatyrosine incorporation than wild-type TyrRS.
The mutant tyrS gene contained a single point mutation resulting in replacement
of phenylalanine by serine at position 130 in the protein. Structural modeling
revealed that position 130 is located close to Asp(182), which directly interacts
with tyrosyladenylate. Kinetic analysis of aminoacyl-tRNA formation by the wild
type and mutated F130S TyrRS enzymes showed that the specificity for azatyrosine,
measured by the ratios of k(cat)/K(m) for tyrosine and the analogue, increased
from 17 to 36 as a result of the F130S mutation. Thus, the high discrimination
against azatyrosine is significantly reduced in the mutant enzyme. These results
suggest that utilization of F130S TyrRS for in vivo protein biosynthesis may lead
to efficient production of azatyrosine-containing alloproteins.
PMID- 11006272
TI - A novel hepatointestinal leukotriene B4 receptor. Cloning and functional
characterization.
AB - Leukotriene B(4) (LTB(4)) is a product of eicosanoid metabolism and acts as an
extremely potent chemotactic mediator for inflammation. LTB(4) exerts positive
effects on the immigration and activation of leukocytes. These effects suggest an
involvement of LTB(4) in several diseases: inflammatory bowel disease, psoriasis,
arthritis, and asthma. LTB(4) elicits actions through interaction with one or
more cell surface receptors that lead to chemotaxis and inflammation. One
leukotriene B(4) receptor has been recently identified (LTB(4)-R1). In this
report we describe cloning of a cDNA encoding a novel 358-amino acid receptor
(LTB(4)-R2) that possesses seven membrane-spanning domains and is homologous
(42%) and genetically linked to LTB(4)-R1. Expression of LTB(4)-R2 is broad but
highest in liver, intestine, spleen, and kidney. In radioligand binding assays,
membranes prepared from COS-7 cells transfected with LTB(4)-R2 cDNA displayed
high affinity (K(d) = 0.17 nm) for [(3)H]LTB(4). Radioligand competition assays
revealed high affinities of the receptor for LTB(4) and LTB(5), and 20-hydroxy
LTB(4), and intermediate affinities for 15(S)-HETE and 12-oxo-ETE. Three LTB(4)
receptor antagonists, 14,15-dehydro-LTB(4), LTB(4)-3-aminopropylamide, and U
75302, had high affinity for LTB(4)-R1 but not for LTB(4)-R2. No apparent
affinity binding for the receptors was detected for the CysLT1-selective
antagonists montelukast and zafirlukast. LTB(4) functionally mobilized
intracellular calcium and inhibited forskolin-stimulated cAMP production in 293
cells. The discovery of this new receptor should aid in further understanding the
roles of LTB(4) in pathologies in these tissues and may provide a tool in
identification of specific antagonists/agonists for potential therapeutic
treatments.
PMID- 11006271
TI - Mechanism of phosphorylation of protein kinase B/Akt by a constitutively active 3
phosphoinositide-dependent protein kinase-1.
AB - Phosphorylation of Thr(308) in the activation loop and Ser(473) at the carboxyl
terminus is essential for protein kinase B (PKB/Akt) activation. However, the
biochemical mechanism of the phosphorylation remains to be characterized. Here we
show that expression of a constitutively active mutant of mouse 3
phosphoinositide-dependent protein kinase-1 (PDK1(A280V)) in Chinese hamster
ovary cells overexpressing the insulin receptor was sufficient to induce PKB
phosphorylation at Thr(308) to approximately the same extent as insulin
stimulation. Phosphorylation of PKB by PDK1(A280V) was not affected by treatment
of cells with inhibitors of phosphatidylinositol 3-kinase or by deletion of the
pleckstrin homology (PH) domain of PKB. C(2)-ceramide, a cell-permeable, indirect
inhibitor of PKB phosphorylation, did not inhibit PDK1(A280V)-catalyzed PKB
phosphorylation in cells and had no effect on PDK1 activity in vitro. On the
other hand, co-expression of full-length protein kinase C-related kinase-1
(PRK1/PKN) or 2 (PRK2) inhibited PDK1(A280V)-mediated PKB phosphorylation.
Replacing alanine at position 280 with valine or deletion of the PH domain
enhanced PDK1 autophosphorylation in vitro. However, deletion of the PH domain of
PDK1(A280V) significantly reduced PDK1(A280V)-mediated phosphorylation of PKB in
cells. In resting cells, PDK1(A280V) localized in the cytosol and at the plasma
membrane. However, PDK1(A280V) lacking the PH domain localized predominantly in
the cytosol. Taken together, our findings suggest that the wild-type PDK1 may not
be constitutively active in cells. In addition, activation of PDK1 is sufficient
to phosphorylate PKB at Thr(308) in the cytosol. Furthermore, the PH domain of
PDK1 may play both positive and negative roles in regulating the in vivo function
of the enzyme. Finally, unlike the carboxyl-terminal fragment of PRK2, which has
been shown to bind PDK1 and allow the enzyme to phosphorylate PKB at both
Thr(308) and Ser(473), full-length PRK2 and its related kinase PRK1/PKN may both
play negative roles in PKB-mediated downstream biological events.
PMID- 11006273
TI - E1A12S-mediated activation of the adenovirus type 12 E2 promoter depends on the
histone acetyltransferase activity of p300/CBP.
AB - Activation of the transcription unit early region 2 (E2) promoter of the
oncogenic adenovirus serotype 12 (Ad12), which regulates the expression of
proteins essential for viral replication, requires the assembly of a ternary
complex consisting of cAMP response element-binding protein (CREB)-1/activating
transcription factor (ATF)-1, the Ad12 12S oncogene product of early region 1A
(E1A(12S)), and the co-activator p300/CBP on the E2(Ad12) cAMP response element
(E2-CRE). Here we show that the active E2(Ad12) promoter is associated with
acetylated histone H4 whereas an E2-CRE point-mutated promoter which is
transcriptionally inactive due to its inability to assemble this ternary complex
is not bound by acetylated histone H4. The histone deacetylase 1 as well as
Roscovitine, which blocks the activation of the histone acetyltransferase (HAT)
activity of CBP by cyclin E-Cdk2, prevents E2(Ad12) promoter activation through
E1A(12S). p300/CBP counteracts the repressive function of histone deacetylase 1
in a HAT domain-dependent manner whereas the p300/CBP-associated factor PCAF
failed to rescue E2(Ad12) promoter activity. E1A(12S) bound p300/CBP displays
strong HAT activity. Most interestingly, E1A(12S)-mediated activation of the
E2(Ad12) promoter correlates well with the ability of the viral protein to
associate with the HAT activity of p300/CBP in vivo. Taken together these data
indicate that the recruitment of the HAT activity of p300/CBP by E1A(12S) plays
an important role in E2(Ad12) promoter activation.
PMID- 11006274
TI - A predicted alpha -helix mediates targeting of the proprotein convertase PC1 to
the regulated secretory pathway.
AB - The proprotein convertase PC1 is a protease whose activity is largely confined to
the dense core secretory granules of neuroendocrine cells. Efficient processing
of PC1 substrates in granules requires a mechanism that will both limit the
activity of the enzyme to these organelles and promote its targeting to the
nascent secretory granules. In the current study, we provide evidence that
targeting of PC1 to secretory granules is mediated by alpha-helical structures in
its C-terminal tail and, at least in part, is dependent on interactions with
specific components of the secretory granule membrane.
PMID- 11006275
TI - Receptor-interacting protein 140 directly recruits histone deacetylases for gene
silencing.
AB - Receptor-interacting protein 140 (RIP140) encodes a histone deacetylase (HDAC)
inhibitor-sensitive repressive activity. Direct interaction of RIP140 with HDAC1
and HDAC3 occurs in vitro and in vivo as demonstrated in co-immunoprecipitation
and glutathione S-transferase pull-down experiments. The HDAC-interacting domain
of RIP140 is mapped to its N-terminal domain, between amino acids 78 and 303
based upon glutathione S-transferase pull-down experiments. In chromatin
immunoprecipitation assays, it is demonstrated that histone deacetylation occurs
at the chromatin region of the Gal4 binding sites as a result of Gal4 DNA binding
domain-tethered RIP expression. The immunocomplexes of RIP140 from cells
transfected with RIP140 and HDAC are able to deacetylate histone proteins in
vitro. This study presents the first evidence for RIP140 as a negative
coregulator for nuclear receptor actions by directly recruiting histone
deacetylases and categorizes RIP140 as a novel negative coregulator that is able
to directly interact with HDACs.
PMID- 11006276
TI - Fidelity and processivity of DNA synthesis by DNA polymerase kappa, the product
of the human DINB1 gene.
AB - Mammalian DNA polymerase kappa (pol kappa), a member of the UmuC/DinB nucleotidyl
transferase superfamily, has been implicated in spontaneous mutagenesis. Here we
show that human pol kappa copies undamaged DNA with average single-base
substitution and deletion error rates of 7 x 10(-3) and 2 x 10(-3), respectively.
These error rates are high when compared to those of most other DNA polymerases.
pol kappa also has unusual error specificity, producing a high proportion of
T.CMP mispairs and deleting and adding non-reiterated nucleotides at
extraordinary rates. Unlike other members of the UmuC/DinB family, pol kappa can
processively synthesize chains of 25 or more nucleotides. This moderate
processivity may reflect a contribution of C-terminal residues, which include two
zinc clusters. The very low fidelity and moderate processivity of pol kappa is
novel in comparison to any previously studied DNA polymerase, and is consistent
with a role in spontaneous mutagenesis.
PMID- 11006277
TI - Structure-function relationships of a novel bacterial toxin, hemolysin E. The
role of alpha G.
AB - The novel pore-forming toxin hemolysin E (HlyE, ClyA, or SheA) consists of a long
four-helix bundle with a subdomain (beta tongue) that interacts with target
membranes at one pole and an additional helix (alpha(G)) that, with the four long
helices, forms a five-helix bundle (tail domain) at the other pole. Random amino
acid substitutions that impair hemolytic activity were clustered mostly, but not
exclusively, within the tail domain, specifically amino acids within, adjacent
to, or interacting with alpha(G). Deletion of amino acids downstream of alpha(G)
did not affect activity, but deletions encompassing alpha(G) yielded insoluble
and inactive proteins. In the periplasm Cys-285 (alpha(G)) is linked to Cys-87
(alpha(B)) of the four-helix bundle via an intramolecular disulfide. Oxidized
HlyE did not form spontaneously in vitro but could be generated by addition of
Cu(II) or mimicked by treatment with Hg(II) salts to yield inactive proteins.
Such treatments did not affect binding to target membranes nor assembly into non
covalently linked octameric complexes once associated with a membrane. However,
gel filtration analyses suggested that immobilizing alpha(G) inhibits
oligomerization in solution. Thus once associated with a membrane, immobilizing
alpha(G) inhibits HlyE activity at a late stage of pore formation, whereas in
solution it prevents aggregation and consequent inactivation.
PMID- 11006278
TI - Arachidonic acid and nonsteroidal anti-inflammatory drugs induce conformational
changes in the human prostaglandin endoperoxide H2 synthase-2 (cyclooxygenase-2).
AB - By using the technique of site-directed spin labeling combined with EPR
spectroscopy, we have observed that binding of arachidonic acid and nonsteroidal
anti-inflammatory drugs induces conformational changes in the human prostaglandin
endoperoxide H(2) synthase enzyme (PGHS-2). Line shape broadening resulting from
spin-spin coupling of nitroxide pairs introduced into the membrane-binding
helices of PGHS-2 was used to calculate the inter-helical distances and changes
in these distances that occur in response to binding various ligands. The inter
residue distances determined for the PGHS-2 holoenzyme using EPR were 1-7.9 A
shorter than those of the crystal structure of the PGHS-2 holoenzyme. However,
inter-helical distances calculated and determined by EPR for PGHS-2 complexed
with arachidonic acid, flurbiprofen, and SC-58125 were in close agreement with
those obtained from the cognate crystal structures. These results indicate that
the structure of the solubilized PGHS-2 holoenzyme measured in solution differs
from the crystal structure of PGHS-2 holoenzyme obtained by x-ray analysis.
Furthermore, binding of ligands induces a conformational change in the holo-PGHS
2, converting it to a structure similar to those obtained by x-ray analysis.
Proteolysis protection assays had previously provided circumstantial evidence
that binding of heme and non-steroidal anti-inflammatory drugs alters the
conformation of PGHS, but the present experiments are the first to directly
measure such changes. The finding that arachidonate can also induce a
conformational change in PGHS-2 was unexpected, and the magnitude of changes
suggests this structural flexibility may be integral to the cyclooxygenase
catalytic mechanism.
PMID- 11006279
TI - Identification of the substrate interaction site in the N-terminal membrane
anchor segment of thromboxane A2 synthase by determination of its substrate
analog conformational changes using high resolution NMR technique.
AB - The present studies describe an investigation for the interaction of N-terminal
membrane anchor domain of thromboxane A(2) synthase (TXAS) with its substrate
analog in a membrane-bound environment using the two-dimensional NMR technique.
TXAS and prostaglandin I(2) synthase (PGIS), respectively, convert the same
substrate, prostaglandin H(2) (PGH(2)), to thromboxane A(2) and prostaglandin
I(2), which have opposite biological functions. Our topology studies have
indicated that the N-terminal region of TXAS has a longer N-terminal endoplasmic
reticulum (ER) membrane anchor region compared with the same segment proposed for
PGIS. The differences in their interaction with the ER membrane may have an
important impact to facilitate their common substrate, PGH(2), across the
membrane into their active sites from the luminal to the cytoplasmic side of the
ER. To test this hypothesis, we first investigated the interaction of the TXAS N
terminal membrane anchor domain with its substrate analog. A synthetic peptide
corresponding to the N-terminal membrane anchor domain (residues 1-35) of TXAS,
which adopted a stable helical structure and exhibited a membrane anchor function
in the membrane-bound environment, was used to interact with a stable PGH(2)
analog,. High resolution two-dimensional NMR experiments, NOESY and TOCSY, were
performed to solve the solution structures of in a membrane-mimicking environment
using dodecylphosphocholine micelles. Different conformations were clearly
observed in the presence and absence of the TXAS N-terminal membrane anchor
domain. Through combination of the two-dimensional NMR experiments, completed
(1)H NMR assignments of were obtained, and the data were used to construct three
dimensional structures of in H(2)O and dodecylphosphocholine micelles, showing
the detailed conformation change upon the interaction with the membrane anchor
domain. The observation supported the presence of a substrate interaction site in
the N-terminal region. The combination of the structural information of and was
able to simulate a solution structure of the unstable TXAS and PGIS substrate,
PGH(2).
PMID- 11006280
TI - Spatial control of Ca2+ signaling by nicotinic acid adenine dinucleotide
phosphate diffusion and gradients.
AB - Intracellular Ca(2+) is able to control numerous cellular responses through
complex spatiotemporal organization. Ca(2+) waves mediated by inositol
trisphosphate or ryanodine receptors propagate by Ca(2+)-induced Ca(2+) release
and therefore do not have an absolute requirement for a gradient in either
inositol trisphosphate or cyclic ADP-ribose, respectively. In contrast, we report
that although Ca(2+) increases induced by nicotinic acid adenine dinucleotide
phosphate (NAADP) are amplified by Ca(2+)-induced Ca(2+) release locally, Ca(2+)
waves mediated by NAADP have an absolute requirement for an NAADP gradient. If
NAADP is increased such that its concentration is spatially uniform in one region
of an egg, the Ca(2+) increase occurs simultaneously throughout this area, and
only where there is diffusion out of this area to establish an NAADP gradient is
there a Ca(2+) wave. A local increase in NAADP results in a Ca(2+) increase that
spreads by NAADP diffusion. NAADP diffusion is restricted at low but not high
concentrations of NAADP, indicating that NAADP diffusion is strongly influenced
by binding to immobile and saturable sites, probably the NAADP receptor itself.
Thus, the range of action of NAADP can be tuned by its concentration from that of
a local messenger, like Ca(2+), to that of a global messenger, like IP(3) or
cyclic ADP-ribose.
PMID- 11006281
TI - Roles of two homotetrameric kinesins in sea urchin embryonic cell division.
AB - To improve our understanding of the roles of microtubule cross-linking motors in
mitosis, we analyzed two sea urchin embryonic kinesin-related proteins. It is
striking to note that both of these proteins behave as homotetramers, but one
behaves as a more compact molecule than the other. These observations suggest
that these two presumptive motors could cross-link microtubules into bundles with
different spacing. Both motors localize to mitotic spindles, and antibody
microinjection experiments suggest that they have mitotic functions. Thus, one of
these kinesin-related proteins may cross-link spindle microtubules into loose
bundles that are "tightened" by the other.
PMID- 11006282
TI - Ribonucleotide reductase, a possible agent in deoxyribonucleotide pool
asymmetries induced by hypoxia.
AB - While investigating the basis for marked natural asymmetries in
deoxyribonucleoside triphosphate (dNTP) pools in mammalian cells, we observed
that culturing V79 hamster lung cells in a 2% oxygen atmosphere causes 2-3-fold
expansions of the dATP, dGTP, and dTTP pools, whereas dCTP declines by a
comparable amount. Others have made similar observations and have proposed that,
because O(2) is required for formation of the catalytically essential oxygen
bridged iron center in ribonucleotide reductase, dCTP depletion at low oxygen
tension results from direct or indirect effects upon ribonucleotide reductase. We
have tested the hypothesis that oxygen limitation affects ribonucleotide
specificity using recombinant mouse ribonucleotide reductase and an assay that
permits simultaneous monitoring of the reduction of all four nucleotide
substrates. Preincubation and assay of the enzyme in an anaerobic chamber caused
only partial activity loss. Accordingly, we treated the enzyme with hydroxyurea,
followed by removal of the hydroxyurea and exposure to atmospheres of varying
oxygen content. The activity was totally depleted by hydroxyurea treatment and
nearly fully regained by exposure to air. By the criterion of activities regained
at different oxygen tensions, we found CDP reduction not to be specifically
sensitive to oxygen depletion; however, GDP reduction was specifically sensitive.
The basis for the differential response to reactivation by O(2) is not known, but
it evidently does not involve varying rates of reactivation of different
allosteric forms of the enzyme or altered response to allosteric effectors at
reduced oxygen tension.
PMID- 11006283
TI - The AROM gene, spliced mRNAs encoding new DNA/RNA-binding proteins are
transcribed from the opposite strand of the melanin-concentrating hormone gene in
mammals.
AB - Melanin-concentrating hormone (MCH) mRNA expression is induced by nerve growth
factor and lithium in PC12 cells, whereas three large MCH RNA species are found
in untreated cells. In this study, we investigated the structures, regulations of
expression, and putative functions of these transcripts. Northern blot, rapid
amplification of cDNA ends-polymerase chain reaction, reverse transcriptase
polymerase chain reaction, and sequencing experiments demonstrated that they are
antisense RNAs complementary to the MCH gene. Two classes of antisense RNAs could
be discriminated as follows: 1) non-coding unspliced RNAs that overlap mainly the
coding part of the MCH gene; 2) spliced variant mRNAs complementary to the 3'
flanking end of the MCH gene and that encode putative proteins containing DNA/RNA
binding domains. We named this new transcriptional unit AROM for antisense-RNA
overlapping-MCH gene. Spliced variant AROM mRNAs are expressed in a broad range
of rat organs. Western blot and immunohistochemistry experiments revealed several
proteins with cytoplasmic but also nuclear localization in PC12 cells. Time
course studies during nerve growth factor and lithium treatment of PC12 cells
indicated a reciprocal regulation of the MCH and AROM gene transcripts, reflected
also at the level of AROM proteins. The major translational product is a 64-kDa
protein (AROM-p64). Recombinant AROM-p64 displayed high binding to single
stranded DNA and poly(A) homopolymers suggesting that this protein could play a
role in mRNA maturation/metabolism.
PMID- 11006284
TI - The protein-tyrosine kinase fer associates with signaling complexes containing
insulin receptor substrate-1 and phosphatidylinositol 3-kinase.
AB - In a screen for 3T3-F442A adipocyte proteins that bind SH2 domains, we isolated a
cDNA encoding Fer, a nonreceptor protein-tyrosine kinase of the Fes/Fps family
that contains a functional SH2 domain. A truncated splicing variant, iFer, was
also cloned. iFer is devoid of both the tyrosine kinase domain and a functional
SH2 domain but displays a unique 42-residue C terminus and retains the ability to
form oligomers with Fer. Expression of both Fer and iFer proteins are strikingly
increased upon differentiation of 3T3-L1 fibroblasts to adipocytes. Platelet
derived growth factor treatment of the cultured adipocytes caused rapid tyrosine
phosphorylation of Fer and its recruitment to complexes containing platelet
derived growth factor receptor and the p85 regulatory subunit of
phosphatidylinositol (PI) 3-kinase. Insulin treatment of 3T3-L1 adipocytes
stimulated association of Fer with complexes containing tyrosine phosphorylated
IRS-1 and PI 3-kinase but did not stimulate tyrosine phosphorylation of Fer. PI 3
kinase activity in anti-Fer immunoprecipitates was also acutely activated by
insulin treatment of cultured adipocytes. These data demonstrate the presence of
Fer tyrosine kinase in insulin signaling complexes, suggesting a role of Fer in
insulin action.
PMID- 11006285
TI - Modeling the late steps in HIV-1 retroviral integrase-catalyzed DNA integration.
AB - Model oligodeoxyribonucleotide substrates representing viral DNA integration
intermediates with a gap and a two-nucleotide 5' overhang were used to examine
late steps in human immunodeficiency virus, type 1 (HIV-1) retroviral integrase
(IN)-catalyzed DNA integration in vitro. HIV-1 or avian myeloblastosis virus
reverse transcriptase (RT) were capable of quantitatively filling in the gap to
create a nicked substrate but did not remove the 5' overhang. HIV-1 IN also
failed to remove the 5' overhang with the gapped substrate. However, with a
nicked substrate formed by RT, HIV-1 IN removed the overhang and covalently
closed the nick in a disintegration-like reaction. The efficiency of this closure
reaction was very low. Such closure was not stimulated by the addition of HMG
(I/Y), suggesting that this protein only acts during the early processing and
joining reactions. Addition of Flap endonuclease-1, a nuclease known to remove 5'
overhangs, abolished the closure reaction catalyzed by IN. A series of base pair
inversions, introduced into the HIV-1 U5 long terminal repeat sequence adjacent
to and/or including the conserved CA dinucleotide, produced no or only a small
decrease in the HIV-1 IN-dependent strand closure reaction. These same mutations
caused a significant decrease in the efficiency of concerted DNA integration by a
modified donor DNA in vitro, suggesting that recognition of the ends of the long
terminal repeat sequence is required only in the early steps of DNA integration.
Finally, a combination of HIV-1 RT, Flap endonuclease-1, and DNA ligase is
capable of quantitatively forming covalently closed DNA with these model
substrates. These results support the hypothesis that cellular enzyme(s) may
catalyze the late steps of retroviral DNA integration.
PMID- 11006286
TI - Differential targeting of beta -adrenergic receptor subtypes and adenylyl cyclase
to cardiomyocyte caveolae. A mechanism to functionally regulate the cAMP
signaling pathway.
AB - Differential modes for beta(1)- and beta(2)-adrenergic receptor (AR) regulation
of adenylyl cyclase in cardiomyocytes is most consistent with spatial regulation
in microdomains of the plasma membrane. This study examines whether caveolae
represent specialized subdomains that concentrate and organize these moieties in
cardiomyocytes. Caveolae from quiescent rat ventricular cardiomyocytes are highly
enriched in beta(2)-ARs, Galpha(i), protein kinase A RIIalpha subunits, caveolin
3, and flotillins (caveolin functional homologues); beta(1)-ARs, m(2)-muscarinic
cholinergic receptors, Galpha(s), and cardiac types V/VI adenylyl cyclase
distribute between caveolae and other cell fractions, whereas protein kinase A
RIalpha subunits, G protein-coupled receptor kinase-2, and clathrin are largely
excluded from caveolae. Cell surface beta(2)-ARs localize to caveolae in
cardiomyocytes and cardiac fibroblasts (with markedly different beta(2)-AR
expression levels), indicating that the fidelity of beta(2)-AR targeting to
caveolae is maintained over a physiologic range of beta(2)-AR expression. In
cardiomyocytes, agonist stimulation leads to a marked decline in the abundance of
beta(2)-ARs (but not beta(1)-ARs) in caveolae. Other studies show co
immunoprecipitation of cardiomyocytes adenylyl cyclase V/VI and caveolin-3,
suggesting their in vivo association. However, caveolin is not required for
adenylyl cyclase targeting to low density membranes, since adenylyl cyclase
targets to low buoyant density membrane fractions of HEK cells that lack
prototypical caveolins. Nevertheless, cholesterol depletion with cyclodextrin
augments agonist-stimulated cAMP accumulation, indicating that caveolae function
as negative regulators of cAMP accumulation. The inhibitory interaction between
caveolae and the cAMP signaling pathway as well as domain-specific differences in
the stoichiometry of individual elements in the beta-AR signaling cascade
represent important modifiers of cAMP-dependent signaling in the heart.
PMID- 11006287
TI - A single regulatory module of the carbamoylphosphate synthetase I gene executes
its hepatic program of expression.
AB - A 469-base pair (bp) upstream regulatory fragment (URF) and the proximal promoter
of the carbamoylphosphate synthetase I (CPS) gene were analyzed for their role in
the regulation of spatial, developmental, and hormone-induced expression in vivo.
The URF is essential and sufficient for hepatocyte-specific expression,
periportal localization, perinatal activation and induction by glucocorticoids,
and cAMP in transgenic mice. Before birth, the transgene is silent but can be
induced by cAMP and glucocorticoids, indicating that these compounds are
responsible for the activation of expression at birth. A 102-bp glucocorticoid
response unit within the URF, containing binding sites for HNF3, C/EBP, and the
glucocorticoid receptor, is the main determinant of the hepatocyte-specific and
hormone-controlled activity. Additional sequences are required for a productive
interaction between this minimal response unit and the core CPS promoter. These
results show that the 469-bp URF, and probably only the 102-bp glucocorticoid
response unit, functions as a regulatory module, in that it autonomously executes
a correct spatial, developmental and hormonal program of CPS expression in the
liver.
PMID- 11006288
TI - TATA-binding protein and the Gal4 transactivator do not bind to promoters
cooperatively.
AB - The yeast Gal4 protein, like many activators, binds TATA-binding protein (TBP)
directly in vitro. It has been speculated that this protein-protein interaction
is important for Gal4p-mediated activation of transcription, but little work has
been done to test specific models involving this interaction. In this study, the
effect of Gal4p on TBP-TATA binding is addressed. Specifically, it is asked if
the Gal4p-TBP interaction can support cooperative binding of the two factors to
promoters. It is easy to see how such an event could stimulate transcription,
particularly from promoters with a non-consensus TATA box. In vitro, however, a
derivative of Gal4p (Gal4-(1-93+768-881)) containing the DNA-binding,
dimerization, and activation domains does not bind to promoter DNA cooperatively
with either recombinant, purified TBP, or with protein from a yeast crude
extract. In vivo, reporter gene experiments using promoters with differing TBP
affinities reveal no major Gal4p-mediated stimulation of TBP function from weak
TATA boxes, as would be predicted if the proteins bind cooperatively.
Furthermore, native Gal4p and a potent Gal4p-based artificial activator lacking a
TBP-binding activation domain support similar ratios of transcription from a
series of promoters identical except for mutations in the TATA box. It is
concluded that Gal4p and TBP do not bind cooperatively to promoters and that this
mechanism does not contribute substantially to Gal4p-mediated transcriptional
activation.
PMID- 11006289
TI - Active DNA topoisomerase IIalpha is a component of the salt-stable centrosome
core.
AB - Recently, we reported that the monoclonal antibody specific for human DNA
topoisomerase IIalpha, Ki-S1, stains not only the nuclei of human A431 cells but
also extranuclear structures suggestive of centrosomes (Meyer, K. N., Kjeldsen,
E., Straub, T., Knudsen, B. K., Kikuchi, A., Hickson, I. D., Kreipe, H., and
Boege, F. (1997) J. Cell Biol. 136, 775-788). Here, we confirm colocalization of
Ki-S1 with the centrosomal marker gamma-tubulin. In addition, we show labeling of
centrosomes by peptide antibodies against the N and C termini of human
topoisomerase IIalpha. Probing Western blots of isolated centrosomes with
topoisomerase IIalpha antibodies, we demonstrate a protein band of 170 kDa.
Moreover, isolated centrosomes exhibited DNA decatenation and relaxation activity
correlated to the amount of topoisomerase IIalpha protein in the same way as seen
in the pure recombinant enzyme. Topoisomerase IIalpha epitopes could not be
removed from centrosomes by salt extraction, DNase treatment, or RNase treatment,
procedures that completely removed the enzyme from nuclei. Taken together, these
observations suggest that active topoisomerase IIalpha is bound tightly to the
centrosome in a DNA-independent manner. Because such centrosomal topoisomerase
IIalpha was also present in quiescent lymphocytes devoid of topoisomerase IIalpha
in the nuclei, we assume that it might be a long-lived storage form.
PMID- 11006290
TI - Age-related macular degeneration. The lipofusion component N-retinyl-N
retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and
induces apoptosis in mammalian retinal pigment epithelial cells.
AB - 10-20% of individuals over the age of 65 suffer from age-related macular
degeneration (AMD), the leading cause of severe visual impairment in humans
living in developed countries. The pathogenesis of this complex disease is poorly
understood, and no efficient therapy or prevention exists to date. A precondition
for AMD appears to be the accumulation of the age pigment lipofuscin in lysosomes
of retinal pigment epithelial (RPE) cells. In AMD, these cells seem to die by
apoptosis with subsequent death of photoreceptor cells, and light may accelerate
the disease process. Intracellular factors leading to cell death are not known.
Here we show that the lipophilic cation N-retinyl-N-retinylidene ethanolamine
(A2E), a lipofuscin component, induces apoptosis in RPE and other cells at
concentrations found in human retina. Apoptosis is accompanied by the appearance
of the proapoptotic proteins cytochrome c and apoptosis-inducing factor in the
cytoplasm and the nucleus. Biochemical examinations show that A2E specifically
targets cytochrome oxidase (COX). With both isolated mitochondria and purified
COX, A2E inhibits oxygen consumption synergistically with light. Inhibition is
reversed by the addition of cytochrome c or cardiolipin, a negatively charged
phospholipid that facilitates the binding of cytochrome c to membranes. Succinate
dehydrogenase activity is not altered by A2E. We suggest that A2E can act as a
proapoptotic molecule via a mitochondria-related mechanism, possibly through site
specific targeting of this cation to COX. Loss of RPE cell viability through
inhibition of mitochondrial function might constitute a pivotal step toward the
progressive degeneration of the central retina.
PMID- 11006291
TI - Sequence requirements for protein-primed initiation and elongation of phage O29
DNA replication.
AB - The double-stranded linear DNA of Bacillus subtilis phage O29 is replicated by a
mechanism in which a terminal protein (TP) acts as a primer. The second 3'
terminal nucleotide of the template directs the incorporation of the 5'-terminal
nucleotide into the TP, giving rise to the initiation complex TP-dAMP. Elongation
then proceeds by a sliding-back mechanism in which the dAMP covalently linked to
the TP pairs to the 3'-terminal nucleotide of the template strand to recover full
length DNA. We have studied the sequence requirements for efficient initiation of
replication using mutated TP-free double-stranded DNA fragments. Efficient
initiation only requires the terminal repetition 5'-AA. The 3'-terminal T,
although not used as template, increases the affinity of DNA polymerase for the
initiator nucleotide; in addition, although to a minor extent, the third 3'
terminal position also directs the formation of the initiation complex and
modulates the initiation rate at the second position. Efficient elongation
requires a previous sliding-back, demanding again a repetition of two nucleotides
at the 3' end; if the sliding-back is prevented, a residual elongation can
proceed directly from the second position or after jumping back from the third to
the first position.
PMID- 11006292
TI - Human alpha (1,3)-fucosyltransferase IV (FUTIV) gene expression is regulated by
elk-1 in the U937 cell line.
AB - The alpha1,3-fucosyltransferase IV (FucTIV) encoded by its gene (FUTIV) is
responsible for synthesis of Le(x) (Galbeta4[Fucalpha3]GlcNAcbeta3Galbeta1,R),
which causes compaction in the morula stage of the preimplantation mouse embryo,
as well as alpha1,3-fucosylation at multiple internal GlcNAc of unbranched poly-N
acetyllactosamine, termed "myeloglycan," the physiological epitope of E-selectin.
Since myeloglycan-type structure is also expressed in various types of human
cancer and may mediate E-selectin-dependent metastasis, expression of FUTIV is
oncodevelopmentally regulated. The mechanisms controlling FUTIV expression remain
to be clarified. In this report, we further characterize FUTIV gene structure and
define a non-TATA box-dependent transcriptional start region just upstream from
the translational start. FUTIV promoter/reporter fusion constructs defined a
"full-length" promoter and highly active fragments in the macrophage-derived U937
and myeloid HL60 cell lines. One highly active fragment contains a consensus
binding site for the Ets-1 transcription factor (Withers, D. A., and Hakomori, S.
(1997) Glycoconj. J. 14, 764). Gel shift analysis shows specific binding to this
site in nuclear extracts from U937 cells. Mutation of the Ets consensus site
significantly reduces FUTIV promoter activity in both cell lines. Gel supershift
and dominant negative cotransfection experiments identified the Ets family member
Elk-1 as one component binding and regulating the FUTIV promoter in U937 cells.
The significance of FUTIV regulation by Elk-1 is discussed.
PMID- 11006293
TI - A general approach for identification of RNA-protein cross-linking sites within
native human spliceosomal small nuclear ribonucleoproteins (snRNPs). Analysis of
RNA-protein contacts in native U1 and U4/U6.U5 snRNPs.
AB - We describe a novel approach to identify RNA-protein cross-linking sites within
native small nuclear ribonucleoprotein (snRNP) particles from HeLa cells. It
combines immunoprecipitation of the UV-irradiated particles under semi-denaturing
conditions with primer extension analysis of the cross-linked RNA moiety. In a
feasibility study, we initially identified the exact cross-linking sites of the
U1 70-kDa (70K) protein in stem-loop I of U1 small nuclear RNA (snRNA) within
purified U1 snRNPs and then confirmed the results by a large-scale preparation
that allowed N-terminal sequencing and matrix-assisted laser desorption
ionization mass spectrometry of purified cross-linked peptide-oligonucleotide
complexes. We identified Tyr(112) and Leu(175) within the RNA-binding domain of
the U1 70K protein to be cross-linked to G(28) and U(30) in stem-loop I,
respectively. We further applied our immunoprecipitation approach to HeLa U5
snRNP, as part of purified 25 S U4/U6.U5 tri-snRNPs. Cross-linking sites between
the U5-specific 220-kDa protein (human homologue of Prp8p) and the U5 snRNA were
located at multiple nucleotides within the highly conserved loop 1 and at one
site in internal loop 1 of U5 snRNA. The cross-linking of four adjacent
nucleotides indicates an extended interaction surface between loop 1 and the 220
kDa protein. In summary, our approach provides a rapid method for identification
of RNA-protein contact sites within native snRNP particles as well as other
ribonucleoprotein particles.
PMID- 11006294
TI - Identification of ISC1 (YER019w) as inositol phosphosphingolipid phospholipase C
in Saccharomyces cerevisiae.
AB - Sphingolipids have emerged as novel bioactive mediators in eukaryotic cells
including yeast. It has been proposed that sphingomyelin (SM) hydrolysis and the
concomitant generation of ceramide are involved in various stress responses in
mammalian cells. The yeast Saccharomyces cerevisiae has inositol
phosphosphingolipids (IPS) instead of SM and glycolipids, and synthesis of IPS is
indispensable to its growth. Although the genes responsible for the synthesis of
IPS have been identified, the gene(s) for the degradation of IPS has not been
reported. Here we show that ISC1 (YER019w), which has homology to bacterial
neutral sphingomyelinase (SMase), encodes IPS phospholipase C (IPS-PLC). First,
we observed that overexpression of ISC1 greatly increased neutral SMase activity,
and this activity was dependent on the presence of phosphatidylserine. Cells
deleted in ISC1 demonstrated negligible neutral SMase activity. Because yeast
cells have IPS instead of SM, we investigated whether IPS are the physiologic
substrates of this enzyme. Lysates of ISC1-overexpressing cells demonstrated very
high PLC activities on IPS. Deletion of ISC1 eliminated endogenous IPS-PLC
activities. Labeling yeast cells with [(3)H]dihydrosphingosine showed that IPS
were increased in the deletion mutant cells. This study identifies the first
enzyme involved in catabolism of complex sphingolipids in S. cerevisiae.
PMID- 11006295
TI - Compromised energetics in the adenylate kinase AK1 gene knockout heart under
metabolic stress.
AB - Rapid exchange of high energy carrying molecules between intracellular
compartments is essential in sustaining cellular energetic homeostasis. Adenylate
kinase (AK)-catalyzed transfer of adenine nucleotide beta- and gamma-phosphoryls
has been implicated in intracellular energy communication and nucleotide
metabolism. To demonstrate the significance of this reaction in cardiac
energetics, phosphotransfer dynamics were determined by [(18)O]phosphoryl oxygen
analysis using( 31)P NMR and mass spectrometry. In hearts with a null mutation of
the AK1 gene, which encodes the major AK isoform, total AK activity and beta
phosphoryl transfer was reduced by 94% and 36%, respectively. This was associated
with up-regulation of phosphoryl flux through remaining minor AK isoforms and the
glycolytic phosphotransfer enzyme, 3-phosphoglycerate kinase. In the absence of
metabolic stress, deletion of AK1 did not translate into gross abnormalities in
nucleotide levels, gamma-ATP turnover rate or creatine kinase-catalyzed
phosphotransfer. However, under hypoxia AK1-deficient hearts, compared with the
wild type, had a blunted AK-catalyzed phosphotransfer response, lowered
intracellular ATP levels, increased P(i)/ATP ratio, and suppressed generation of
adenosine. Thus, although lack of AK1 phosphotransfer can be compensated in the
absence of metabolic challenge, under hypoxia AK1-knockout hearts display
compromised energetics and impaired cardioprotective signaling. This study,
therefore, provides first direct evidence that AK1 is essential in maintaining
myocardial energetic homeostasis, in particular under metabolic stress.
PMID- 11006296
TI - Novel catalytic mechanism of nucleophilic substitution by asparagine residue
involving cyanoalanine intermediate revealed by mass spectrometric monitoring of
an enzyme reaction.
AB - l-2-Haloacid dehalogenase from Pseudomonas sp. YL catalyzes the hydrolytic
dehalogenation, in which Asp(10) acts as a nucleophile to attack the alpha-carbon
of l-2-haloalkanoates to form an ester intermediate, which is subsequently
hydrolyzed to produce d-2-hydroxyalkanoates. Surprisingly, replacement of the
catalytic residue, Asp(10), by Asn did not result in total inactivation of the
enzyme (Kurihara, T., Liu, J.-Q., Nardi-Dei, V., Koshikawa, H., Esaki, N., and
Soda, K. (1995) J. Biochem. 117, 1317-1322). In this study, we monitored the D10N
mutant enzyme reaction by ion-spray mass spectrometry, and found that the enzyme
shows a unique structural change when it was incubated with the substrate, l-2
chloropropionate. LC/MS and tandem MS/MS analyses revealed that Asn(10) attacks
the substrate to form an imidate, and a proton and d-lactic acid are eliminated
to produce a nitrile (beta-cyanoalanine residue), followed by hydrolysis to
reproduce Asn(10). This is the first report of the function of Asn to catalyze
nucleophilic substitution through its conversion to beta-cyanoalanine residue as
an intermediate structure. Also, these results demonstrate that mass spectrometry
is remarkably useful in monitoring enzyme reactions.
PMID- 11006297
TI - Regulation of protein kinase C by the cytoskeletal protein calponin.
AB - Previous studies from this laboratory have shown that, upon agonist activation,
calponin co-immunoprecipitates and co-localizes with protein kinase Cepsilon
(PKCepsilon) in vascular smooth muscle cells. In the present study we demonstrate
that calponin binds directly to the regulatory domain of PKC both in overlay
assays and, under native conditions, by sedimentation with lipid vesicles.
Calponin was found to bind to the C2 region of both PKCepsilon and PKCalpha with
possible involvement of C1B. The C2 region of PKCepsilon binds to the calponin
repeats with a requirement for the region between amino acids 160 and 182. We
have also found that calponin can directly activate PKC autophosphorylation. By
using anti-phosphoantibodies to residue Ser-660 of PKCbetaII, we found that
calponin, in a lipid-independent manner, increased auto-phosphorylation of
PKCalpha, -epsilon, and -betaII severalfold compared with control conditions.
Similarly, calponin was found to increase the amount of (32)P-labeled phosphate
incorporated into PKC from [gamma-(32)P]ATP. We also observed that calponin
addition strongly increased the incorporation of radiolabeled phosphate into an
exogenous PKC peptide substrate, suggesting an activation of enzyme activity.
Thus, these results raise the possibility that calponin may function in smooth
muscle to regulate PKC activity by facilitating the phosphorylation of PKC.
PMID- 11006298
TI - Mechanism of chalcone synthase. pKa of the catalytic cysteine and the role of the
conserved histidine in a plant polyketide synthase.
AB - Polyketide synthases (PKS) assemble structurally diverse natural products using a
common mechanistic strategy that relies on a cysteine residue to anchor the
polyketide during a series of decarboxylative condensation reactions that build
the final reaction product. Crystallographic and functional studies of chalcone
synthase (CHS), a plant-specific PKS, indicate that a cysteine-histidine pair
(Cys(164)-His(303)) forms part of the catalytic machinery. Thiol-specific
inactivation and the pH dependence of the malonyl-CoA decarboxylation reaction
were used to evaluate the potential interaction between these two residues.
Inactivation of CHS by iodoacetamide and iodoacetic acid targets Cys(164) in a pH
dependent manner (pK(a) = 5.50). The acidic pK(a) of Cys(164) suggests that an
ionic interaction with His(303) stabilizes the thiolate anion. Consistent with
this assertion, substitution of a glutamine for His(303) maintains catalytic
activity but shifts the pK(a) of the thiol to 6.61. Although the H303A mutant was
catalytically inactive, the pH-dependent incorporation of [(14)C]iodoacetamide
into this mutant exhibits a pK(a) = 7.62. Subsequent analysis of the pH
dependence of the malonyl-CoA decarboxylation reaction catalyzed by wild-type CHS
and the H303Q and C164A mutants also supports the presence of an ion pair at the
CHS active site. Structural and sequence conservation of a cysteine-histidine
pair in the active sites of other PKS implies that a thiolate-imidazolium ion
pair plays a central role in polyketide biosynthesis.
PMID- 11006299
TI - Neuronal Ca2+ sensor-1/frequenin functions in an autocrine pathway regulating
Ca2+ channels in bovine adrenal chromaffin cells.
AB - NCS-1/frequenin belongs to a family of EF-hand-containing Ca(2+) sensors
expressed mainly in neurons. Overexpression of NCS-1/frequenin has been shown to
stimulate neurotransmitter release but little else is known of its cellular
roles. We have constructed an EF-hand mutant, NCS-1(E120Q), as a likely dominant
inhibitor of cellular NCS-1 function. Recombinant NCS-1(E120Q) showed an impaired
Ca(2+)-dependent conformational change but could still bind to cellular proteins.
Transient expression of this mutant, but not NCS-1, in bovine adrenal chromaffin
cells increased non-L-type Ca(2+) channel currents. Cells expressing NCS-1(E120Q)
no longer responded effectively to the removal of autocrine purinergic/opioid
inhibition of Ca(2+) currents but still showed voltage-dependent facilitation.
These data are consistent with the existence of both voltage-dependent and
voltage-independent pathways for Ca(2+) channel inhibition in chromaffin cells.
Our results suggest a novel function for NCS-1 specific for the voltage
independent autocrine pathway that negatively regulates non-L-type Ca(2+)
channels in chromaffin cells.
PMID- 11006300
TI - Turgor, temperature and the growth of plant cells: using Chara corallina as a
model system.
AB - Rapid changes in turgor pressure (P:) and temperature (T:) are giving new
information about the mechanisms of plant growth. In the present work, single
internode cells of the large-celled alga Chara corallina were used as a model for
plant growth. P was changed without altering the chemical environment of the wall
while observing growth without elastic changes. When P: was measured before any
changes, the original growth rate bore no relationship to the original P.
However, if P of growing cells was decreased, growth responded immediately
without evidence for rapid changes in wall physical properties. Growth occurred
only above a 0.3 MPa threshold, and increasing P caused small increases in growth
that became progressively larger as P rose, resulting in a curvilinear response
overall. The small changes in growth close to the threshold may explain early
failures to detect these responses. When T was lowered, the elastic properties of
the cell were unaffected, but growth was immediately inhibited. The lower T
caused P to decrease, but returning P to its original value did not return growth
to its original rate. The decreased P at low T occurred because of T effects on
the osmotic potential of the cell. At above-normal P, growth partially resumed at
low T Therefore, growth required a P-sensitive process that was also T-sensitive.
Because elastic properties were little affected by T, but growth was markedly
affected, the process is likely to involve metabolism. The rapidity of its
response to P and T probably excludes the participation of changes in gene
expression.
PMID- 11006301
TI - Water relations and leaf expansion: importance of time scale.
AB - The role of leaf water relations in controlling cell expansion in leaves of water
stressed maize and barley depends on time scale. Sudden changes in leaf water
status, induced by sudden changes in humidity, light and soil salinity, greatly
affect leaf elongation rate, but often only transiently. With sufficiently large
changes in salinity, leaf elongation rates are persistently reduced. When plants
are kept fully turgid throughout such sudden environmental changes, by placing
their roots in a pressure chamber and raising the pressure so that the leaf xylem
sap is maintained at atmospheric pressure, both the transient and persistent
changes in leaf elongation rate disappear. All these responses show that water
relations are responsible for the sudden changes in leaf elongation rate
resulting from sudden changes in water stress and putative root signals play no
part. However, at a time scale of days, pressurization fails to maintain high
rates of leaf elongation of plants in either saline or drying soil, indicating
that root signals are overriding water relations effects. In both saline and
drying soil, pressurization does raise the growth rate during the light period,
but a subsequent decrease during the dark results in no net effect on leaf growth
over a 24 h period. When transpirational demand is very high, however, growth
promoting effects of pressurization during the light period outweigh any
reductions in the dark, resulting in a net increase in growth of pressurized
plants over 24 h. Thus leaf water status can limit leaf expansion rates during
periods of high transpiration despite the control exercised by hormonal effects
on a 24 h basis.
PMID- 11006302
TI - Spatial distributions of expansion rate, cell division rate and cell size in
maize leaves: a synthesis of the effects of soil water status, evaporative demand
and temperature.
AB - The spatial distributions of leaf expansion rate, cell division rate and cell
size was examined under contrasting soil water conditions, evaporative demands
and temperatures in a series of experiments carried out in either constant or
naturally fluctuating conditions. They were examined in the epidermis and all
leaf tissues. (1) Meristem temperature affected relative elongation rate by a
constant ratio at all positions in the leaf. If expressed per unit thermal time,
the distribution of relative expansion rate was independent of temperature and
was similar in all experiments with low evaporative demand and no water deficit.
This provides a reference distribution, characteristic of the studied genotype,
to which any distribution in stressed plants can be compared. (2) Evaporative
demand and soil water deficit affected independently the distribution of relative
elongation rate and had near-additive effects. For a given stress, a nearly
constant difference was observed, at all positions of the leaf, between the
relative elongation rates of stressed plants and those of control plants. This
caused a reduction in the length of the zone with tissue elongation. (3) Methods
for calculating cell division rate in the epidermis and in all leaf tissues are
proposed and discussed. In control plants, the zone with cell division was 30 mm
and 60 mm long in the epidermis and in whole tissues, respectively. Both this
length and relative division rate were reduced by soil water deficit. The size of
epidermal and of mesophyll cells was nearly unaffected in the leaf zone with both
cell division and tissue expansion, suggesting that water deficit affects tissue
expansion rate and cell division rate to the same extent. Conversely, cell size
of epidermis and mesophyll were reduced by water deficit in mature parts of the
leaf.
PMID- 11006303
TI - Leaf development in Ricinus communis during drought stress: dynamics of growth
processes, of cellular structure and of sink-source transition.
AB - Dicot leaf growth is characterized by partly transient tip-to-base gradients of
growth processes, structure and function. These gradients develop dynamically and
interact with dynamically developing stress conditions like drought. In Ricinus
communis plants growing under well-watered and drought conditions growth rates
peaked during the late night and minimal values occurred in the late afternoon.
During this diurnal course the leaf base always showed much higher rates than the
leaf tip. The amplitude of this diurnal course decreased when leaves approached
maturity and during drought stress without any significant alteration of the
diurnal pattern and it increased during the first days after rewatering. Unique
relationships between leaf size and cytological structure were observed. This
provided the framework for the analysis of changes in assimilation, transpiration
and dark respiration, chlorophyll, protein, carbohydrate, and amino acid
concentrations, and of activities of sink-source-related enzymes at the leaf tip
and base during leaf development in well-watered and drought-stressed plants. Gas
exchange was dominated by physiological rather than by anatomical properties
(stomatal density). Tip-to-base gradients in carbohydrate concentrations per dry
weight and sink-source-related enzymes were absent, whereas significant gradients
were found in amino acid concentrations per dry weight. During drought stress,
growing leaves developed source function at smaller leaf size, before specific
physiological adaptations to drought occurred. The relevance of the developmental
status of individual leaves for the drought-stress response and of the structural
changes for the biochemical composition changes is discussed.
PMID- 11006304
TI - Water uptake by roots: effects of water deficit.
AB - The variable hydraulic conductivity of roots (Lp(r)) is explained in terms of a
composite transport model. It is shown how the complex, composite anatomical
structure of roots results in a composite transport of both water and solutes. In
the model, the parallel apoplastic and cell-to-cell (symplastic and
transcellular) pathways play an important role as well as the different tissues
and structures arranged in series within the root cylinder (epidermis, exodermis,
cortex, endodermis, stelar parenchyma). The roles of Casparian bands and suberin
lamellae in the root's endo- and exodermis are discussed. Depending on the
developmental state of these apoplastic barriers, the overall hydraulic
resistance of roots is either more evenly distributed across the root cylinder
(young unstressed roots) or is concentrated in certain layers (exo- and
endodermis in older stressed roots). The reason for the variability of root
Lp(r), is that hydraulic forces cause a dominating apoplastic flow of water
around protoplasts, even in the endodermis and exodermis. In the absence of
transpiration, water flow is osmotic in nature which causes a high resistance as
water passes across many membranes on its passage across the root cylinder. The
model allows for a high capability of roots to take up water in the presence of
high rates of transpiration (high demands for water from the shoot). By contrast,
the hydraulic conductance is low, when transpiration is switched off. Overall,
this results in a non-linear relationship between water flow and forces
(gradients of hydrostatic and osmotic pressure) which is otherwise hard to
explain. The model allows for special root characteristics such as a high
hydraulic conductivity (water permeability) in the presence of a low permeability
of nutrient ions once taken up into the stele by active processes. Low root
reflection coefficients are in line with the idea of some apoplastic bypasses for
water within the root cylinder. According to the composite transport model, the
switch from the hydraulic to the osmotic mode is purely physical. In the presence
of heavily suberized roots, the apoplastic component of water flow may be too
small. Under these conditions, a regulation of radial water flow by water
channels dominates. Since water channels are under metabolic control, this
component represents an 'active' element of regulation. Composite transport
allows for an optimization of the water balance of the shoot in addition to the
well-known phenomena involved in the regulation of water flow (gas exchange)
across stomata. The model is employed to explain the responses of plants to water
deficit and other stresses. During water deficit, the cohesion-tension mechanism
of the ascent of sap in the xylem plays an important role. Results are summarized
which prove the validity of the coehesion/tension theory. Effects of the stress
hormone abscisic acid (ABA) are presented. They show that there is an apoplastic
component of the flow of ABA in the root which contributes to the ABA signal in
the xylem. On the other hand, (+)-cis-trans-ABA specifically affects both the
cell level (water channel activity) and water flow driven by gradients in osmotic
pressure at the root level which is in agreement with the composite transport
model. Hydraulic water flow in the presence of gradients in hydrostatic pressure
remains unchanged. The results agree with the composite transport model and
resemble earlier findings of high salinity obtained for the cell (Lp) and root
(Lp(r)) level. They are in line with known effects of nutrient deprivation on
root Lp(r )and the diurnal rhythm of root Lp(r )recently found in roots of LOTUS.
PMID- 11006305
TI - Adaptation of roots to low water potentials by changes in cell wall extensibility
and cell wall proteins.
AB - It is common for the root/shoot ratio of plants to increase when water
availability is limiting. This ratio increases because roots are less sensitive
than shoots to growth inhibition by low water potentials. The physiological and
molecular mechanisms that assist root growth under drought conditions are
reviewed, with a focus on changes in cell walls. Maize seedlings adapt to low
water potential by making the walls in the apical part of the root more
extensible. In part, this is accomplished by increases in expansin activity and
in part by other, more complex changes in the wall. The role of xyloglucan
endotransglycosylase, peroxidase and other wall enzymes in root adaptation to low
water potential is evaluated and some of the complications in the field of study
are listed.
PMID- 11006306
TI - Growth of Arabidopsis thaliana seedlings under water deficit studied by control
of water potential in nutrient-agar media.
AB - We have characterized the growth responses of Arabidopsis thaliana seedlings to
water deficit. To manipulate the water potential, we developed a method whereby
the nutrient-agar medium could be supplemented with polyethylene glycol (PEG
8000); PEG was introduced into gelled media by diffusion, which produced media
with water potential as low as -1.6 MPa. For dark-grown plants, hypocotyl growth
had a hyperbolic dependence on water potential, and was virtually stopped by -1
MPa. In contrast, primary root elongation was stimulated by moderate deficit and
even at -1.6 MPa was not significantly less than the control. That these results
did not depend on a direct effect of PEG was attested by obtaining
indistinguishable results when a dialysis membrane impermeable to PEG was placed
between the medium and the seedlings. For light-grown seedlings, moderate deficit
also stimulated primary root elongation and severe deficit reduced elongation
only partially. These changes in elongation were paralleled by changes in root
system dry weight. At moderate deficit, lateral root elongation and initiation
were unaffected and at higher stress levels both were inhibited. Primary root
diameter increased steadily with time in well-watered controls and under water
deficit increased transiently before stabilizing at a diameter that was inversely
proportional to the deficit. Along with stimulated primary root elongation,
moderate water deficit also stimulated the rate of cell production. Thus, A.
thaliana responds to water deficit vigorously, which enhances its use as a model
to uncover mechanisms underlying plant responses to water deficit.
PMID- 11006307
TI - Control of abscisic acid synthesis.
AB - The abscisic acid (ABA) biosynthetic pathway involves the formation of a 9-cis
epoxycarotenoid precursor. Oxidative cleavage then results in the formation of
xanthoxin, which is subsequently converted to ABA. A number of steps in the
pathway may control ABA synthesis, but particular attention has been given to the
enzyme involved in the oxidative cleavage reaction, i.e. 9-cis-epoxycarotenoid
dioxygenase (NCED). Cloning of a gene encoding this enzyme in maize was first
reported in 1997. Mapping and DNA sequencing studies indicated that a wilty
tomato mutant was due to a deletion in the gene encoding an enzyme with a very
similar amino acid sequence to this maize NCED. The potential use of this gene in
altering ABA content will be discussed together with other genes encoding ABA
biosynthetic enzymes.
PMID- 11006308
TI - Endogenous ABA maintains shoot growth in tomato independently of effects on plant
water balance: evidence for an interaction with ethylene.
AB - To examine whether the reduced shoot growth of abscisic acid (ABA)-deficient
mutants of tomato is independent of effects on plant water balance, flacca and
notabilis were grown under controlled-humidity conditions so that their leaf
water potentials were equal to or higher than those of well-watered wild-type
plants throughout development. Most parameters of shoot growth remained markedly
impaired and root growth was also greatly reduced. Additional experiments with
flacca showed that shoot growth substantially recovered when wild-type levels of
ABA were restored by treatment with exogenous ABA, even though improvement in
leaf water potential was prevented. The ability of applied ABA to increase growth
was greatest for leaf expansion, which was restored by 75%. The ethylene
evolution rate of growing leaves was doubled in flacca compared to the wild type
and treatment with silver thiosulphate to inhibit ethylene action partially
restored shoot growth. The results demonstrate that normal levels of endogenous
ABA are required to maintain shoot development, particularly leaf expansion, in
well-watered tomato plants, independently of effects on plant water balance. The
impairment of shoot growth caused by ABA deficiency is at least partly
attributable to ethylene.
PMID- 11006309
TI - The effects of ABA on channel-mediated K(+) transport across higher plant roots.
AB - The transport and accumulation of K(+) in higher plant roots is regulated by ABA.
Molecular and electrophysiological techniques have identified a number of
discrete transporters which are involved in the translocation of K(+) from the
soil solution to the shoots of higher plants. Furthermore, recent reports have
shown that ABA regulates K(+) channel activity in maize and Arabidopsis roots
which suggests that ABA regulation of K(+) transport in roots is, at least in
part, ion channel-mediated. The signalling processes which underlie the ABA
regulation of K(+) channels have been investigated. The effects of ABA on the
membrane potential of intact maize root cells were also studied. It was found
that ABA regulated the membrane potential of root cells and that this regulation
is consistent with the hypothesis that ABA-induced K(+) accumulation in roots is
mediated by K(+) channels.
PMID- 11006310
TI - Sensitivity of growth of roots versus leaves to water stress: biophysical
analysis and relation to water transport.
AB - Water transport is an integral part of the process of growth by cell expansion
and accounts for most of the increase in cell volume characterizing growth. Under
water deficiency, growth is readily inhibited and growth of roots is favoured
over that of leaves. The mechanisms underlying this differential response are
examined in terms of Lockhart's equations and water transport. For roots, when
water potential (psi) is suddenly reduced, osmotic adjustment occurs rapidly to
allow partial turgor recovery and re-establishment of psi gradient for water
uptake, and the loosening ability of the cell wall increases as indicated by a
rapid decline in yield-threshold turgor. These adjustments permit roots to resume
growth under low psi. In contrast, in leaves under reductions in psi of similar
magnitude, osmotic adjustment occurs slowly and wall loosening ability either
does not increase substantially or actually decreases, leading to marked growth
inhibition. The growth region of both roots and leaves are hydraulically isolated
from the vascular system. This isolation protects the root from low psi in the
mature xylem and facilitates the continued growth into new moist soil volume.
Simulations with a leaky cable model that includes a sink term for growth water
uptake show that growth zone psi is barely affected by soil water removal through
transpiration. On the other hand, hydraulic isolation dictates that psi of the
leaf growth region would be low and subjected to further reduction by high
evaporative demand. Thus, a combination of transport and changes in growth
parameters is proposed as the mechanism co-ordinating the growth of the two
organs under conditions of soil moisture depletion. The model simulation also
showed that roots behave as reversibly leaky cable in water uptake. Some field
data on root water extraction and vertical profiles of psi in shoots are viewed
as manifestations of these basic phenomena. Also discussed is the trade-off
between high xylem conductance and strong osmotic adjustment.
PMID- 11006311
TI - Regulation of leaf and fruit growth in plants growing in drying soil:
exploitation of the plants' chemical signalling system and hydraulic architecture
to increase the efficiency of water use in agriculture.
AB - In this paper the nature of root-to-shoot signals in plants growing in drying
soil is considered in the context of their commercial exploitation in tomato
(Lycopersicon esculentum L.) and other crops. Recent findings are presented on
the effects of partial root drying (PRD) in the production of a glasshouse tomato
crop. These findings show how an understanding of both root-to-shoot signalling
mechanisms and fruit hydraulic architecture may explain observed increases in
fruit quality, the differential effects of PRD on vegetative and reproductive
production and the incidence of blossom end rot. Evidence is provided to support
the hypothesis that the success of PRD may lie, at least in part, in the relative
chemical and hydraulic isolation of the tomato fruit.
PMID- 11006312
TI - Hormonal changes induced by partial rootzone drying of irrigated grapevine.
AB - Partial rootzone drying (PRD) is a new irrigation technique which improves the
water use efficiency (by up to 50%) of wine grape production without significant
crop reduction. The technique was developed on the basis of knowledge of the
mechanisms controlling transpiration and requires that approximately half of the
root system is always maintained in a dry or drying state while the remainder of
the root system is irrigated. The wetted and dried sides of the root system are
alternated on a 10-14 d cycle. Abscisic acid (ABA) concentration in the drying
roots increases 10-fold, but ABA concentration in leaves of grapevines under PRD
only increased by 60% compared with a fully irrigated control. Stomatal
conductance of vines under PRD irrigation was significantly reduced when compared
with vines receiving water to the entire root system. Grapevines from which water
was withheld from the entire root system, on the other hand, show a similar
reduction in stomatal conductance, but leaf ABA increased 5-fold compared with
the fully irrigated control. PRD results in increased xylem sap ABA concentration
and increased xylem sap pH, both of which are likely to result in a reduction in
stomatal conductance. In addition, there was a reduction in zeatin and zeatin
riboside concentrations in roots, shoot tips and buds of 60, 50 and 70%,
respectively, and this may contribute to the reduction in shoot growth and
intensified apical dominance of vines under PRD irrigation. There is a nocturnal
net flux of water from wetter roots to the roots in dry soil and this may assist
in the distribution of chemical signals necessary to sustain the PRD effect. It
was concluded that a major effect of PRD is the production of chemical signals in
drying roots that are transported to the leaves where they bring about a
reduction in stomatal conductance.
PMID- 11006313
TI - Expression of the adrenomedullin gene in epithelial ovarian cancer.
AB - Adrenomedullin (AM) gene expression was analysed in 60 cases of epithelial
ovarian cancer, (29 serous, 14 mucinous, 13 endometrioid, three clear cell, and
one undifferentiated) using reverse transcription-polymerase chain reaction (RT
PCR); 10 of the cases were of low malignant potential; 25 were stage I; three
were stage II; 27 were stage III; and five were stage IV. The level of AM gene
expression was described in terms of the relative yield of the AM gene to the
beta2-microglobulin gene. AM gene expression ranged from 0.04 to 1.57 (median
0.36). The association between histological grade and AM gene expression was
significant (P: = 0.027), however, the association with other clinico
pathological features, i.e. patients' age at diagnosis, stage of disease,
residual tumour mass after initial surgery, and histological subtype were not
significant. Survival data were available for all patients and univariate Cox
regression analysis showed that the AM gene expression was significantly
associated with a poor prognosis (P: = 0.019). Immunohistochemical studies showed
that AM was localized in the outer cell membrane or the cytoplasm of the
carcinoma cells and in the endothelial cells of the tumour stroma. The AM gene
expression level may play a key role in the biology of epithelial ovarian cancer
and may define a more aggressive tumour phenotype.
PMID- 11006314
TI - No evidence for mutations of the leptin or leptin receptor genes in women with
polycystic ovary syndrome.
AB - Polycystic ovarian syndrome (PCOS) is often associated with obesity and insulin
resistance, both of which are features that are linked to the leptin and leptin
receptor (LEPR) genes. Analysis of the leptin gene by sequencing samples from 38
well-characterized patients with PCOS revealed no mutations of the coding exons.
In single-stranded conformational polymorphism (SSCP) analysis and subsequent
sequencing of the LEPR gene revealed previously identified amino acid variants in
exons 2, 4 and 12 as well as the pentanucleotide insertion in the 3'-untranslated
region (3'-UTR). The allele frequencies of these polymorphisms did not differ
from those in the general population, as assessed in 122 female controls.
Compared with non-carriers, serum insulin concentrations tended to be lower in
the carriers of the variant LEPR exon 12 allele as well as in the carriers of the
variant LEPR 3'-UTR allele, a marker previously suggested to be associated with
serum insulin concentrations. In conclusion, PCOS is not commonly a consequence
of mutations of the leptin or LEPR genes. However, our data support the
hypothesis that variations in the LEPR gene locus have an effect on insulin
regulation.
PMID- 11006315
TI - The effect of FSH on male germ cell survival and differentiation in vitro is
mimicked by pentoxifylline but not insulin.
AB - High concentrations of FSH have been shown to boost in-vitro differentiation of
germ cells from men with normal spermatogenesis and from some patients with in
vivo maturation arrest. This study shows that the differentiation-promoting
effect of FSH is connected to protection against germ cell apoptosis and that
both effects can be mimicked by the intracellular cyclic AMP (cAMP)-elevating
drug pentoxifylline. On the other hand, a high concentration of insulin, supposed
to act at the insulin-like growth factor I receptor, did not exert any effect
either on differentiation or apoptosis of germ cells in vitro. These data show
that the in-vitro effects of supraphysiological concentrations of FSH on human
spermatogenesis are mediated by the classical FSH signal transduction pathway
involving cAMP as a second messenger. Pentoxifylline may thus be useful as an
alternative means for intracellular cAMP elevation in men with high circulating
FSH concentrations leading to desensitization of the FSH receptor.
PMID- 11006316
TI - Prostasomes inhibit the NADPH oxidase activity of human neutrophils.
AB - Prostasomes are particular lipid vesicles secreted by the prostate in human semen
and involved in several physiological functions such as the improvement of sperm
motility or immunomodulation. We have previously shown that they reduced the
overall reactive oxygen species (ROS) production of seminal polymorphonuclear
neutrophils (PMN). The present study was conducted to define the mechanism by
which prostasomes inhibit the ROS production of blood and seminal PMN. The
luminol chemiluminescence measuring total ROS production of blood PMN stimulated
by either a phorbol ester (PMA) or a chemoattractant peptide, formyl-Met-Leu-Phe
(fMLP) was significantly inhibited by prostasomes. The NADPH oxidase activity of
the PMN was measured by 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1, 2
a]pyrazin-3-one (MCLA) chemiluminescence. Prostasomes inhibited the NADPH oxidase
activity of blood or seminal PMN and increased the lag-phase of the enzyme after
PMA stimulation. Prostasomes also inhibited significantly the NADPH oxidase
activity of fMLP stimulated blood PMN, but the inhibition was not significant for
seminal PMN. The lipid composition of blood PMN was analysed and compared to the
lipid composition of prostasomes. This showed that prostasomes had a high
cholesterol:phospholipid molar ratio and a high proportion of sphingomyelin.
Together with the fact that prostasomes can rigidify the plasma membrane of blood
PMN, these results led us to postulate that prostasomes inhibit the NADPH oxidase
activity of PMN by lipid transfer from the prostasomes to the plasma membrane of
the PMN.
PMID- 11006317
TI - Acrosome reaction of human spermatozoa is mainly mediated by alpha1H T-type
calcium channels.
AB - The objectives of this study were: (i) to investigate the possible role of T-type
Ca(2+) channels on the acrosome reaction (AR) of human spermatozoa; and (ii) to
determine the sub-type of T-type calcium channels involved in the AR. The AR was
induced in vitro by mannose-bovine serum albumin (BSA). The inhibitory effects of
mibefradil (T-type Ca(2+) channel blocker), NiCl(2), or nifedipine (L-type Ca(2+)
channel blocker) on the mannose-BSA induced AR were evaluated in capacitated
human spermatozoa. The AR was sensitively inhibited by low micromolar
concentrations of mibefradil (IC(50) = 1 micromol/l) in a dose-dependent manner.
Low concentrations of Ni(2+) (IC(50) = 40 micromol/l) also inhibited the mannose
BSA induced AR. On the contrary, higher concentrations of nifedipine were
required to block AR (IC(50) = 60 micromol/l). Reverse transcription-polymerase
chain reaction (RT-PCR) was performed to identify the sub-types of T-type
channels present in human testes. Analysis of PCR products showed that only
alpha1H subunits are expressed in testes. The expression of the alpha1H subunit
may be tissue specific since its mRNA was not detected in the human ovary. The
present study suggests that the AR of human spermatozoa is highly associated with
T-type Ca(2+) channels and is mainly mediated by calcium influx through alpha1H T
type Ca(2+) channels.
PMID- 11006318
TI - In-vitro studies of the potential role of neutrophils in the process of
menstruation.
AB - Significant numbers of neutrophils are found extravascularly within the
endometrium only during the immediate premenstrual and menstrual phases of the
cycle. In this study we investigated the effect of neutrophil products on the
synthesis and activation of matrix metalloproteinases (MMP), enzymes considered
to play a crucial role in the degradation of endometrial tissue that occurs at
menstruation. Latent MMP-2, MMP-3 and MMP-9 released by endometrial stromal
fibroblasts and peripheral blood neutrophils were activated when the two cell
types were cultured together. Tissue inhibitors of metalloproteinases (TIMP) 1
and 2 were also degraded in this system. Neutralization studies identified a role
for the serine protease, elastase, in the observed activation of MMP. Although
cultured endometrial neutrophils behaved similarly to peripheral blood
neutrophils in their ability to release latent MMP-9 and elastase, no active
forms of MMP-2. MMP-3 and MMP-9 were detected in supernatant from co-cultures
containing endometrial neutrophils and stromal fibroblasts. This appeared to be
due to an alteration in the neutrophil production of elastase and inhibitors.
e.g. alpha1-antitrypsin, in these cultures so that active elastase was not
available. Our results demonstrate that any involvement of neutrophils in the
tissue destruction occurring at menstruation may be tightly regulated by the
focal concentration of degradative enzymes and their respective inhibitors.
PMID- 11006319
TI - Expression of interleukin-11 during the human menstrual cycle: coincidence with
stromal cell decidualization and relationship to leukaemia inhibitory factor and
prolactin.
AB - Interleukin-11 (IL-11) is crucial in the decidualization response of the uterine
stroma to the implanting blastocyst in the mouse. This study examined the
localization and expression of IL-11 in human endometrium throughout the
menstrual cycle and of prolactin and leukaemia inhibitory factor (LIF) in
secretory phase endometrium. The mRNA expression of IL-11 receptor alpha and the
signalling component, gp130, in endometrial tissue were also determined.
Immunoreactive IL-11 was highest in the secretory phase and present in
decidualized stromal cells, glandular epithelial cells, endothelial and smooth
muscle cells, and the mRNA expression was verified by in-situ hybridization.
Decidual cells showed the most intense staining. IL-11 receptor alpha and gp130
mRNA were detected throughout the cycle with minimal variation. Expression of IL
11 mRNA and protein preceded that of prolactin. While immunoreactive prolactin
was found in stromal, decidual and glandular epithelial cells, prolactin mRNA was
confined to decidual cells. In contrast, endometrial LIF expression preceded IL
11 but was largely confined to the glandular epithelium. The sequence of
appearance of LIF, IL-11 and prolactin suggests a synchronized role for each in
the differentiation of the endometrium. The cyclical changes and cell type
specific expression of IL-11 suggests a potential role in the decidualization of
stromal cells.
PMID- 11006320
TI - Gene expression and tissue concentrations of IGF-I in human myometrium and
fibroids under different hormonal conditions.
AB - The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA
and protein level in myometrium and fibroids from women with and without
preoperative treatment with a gonadotrophin-releasing hormone (GnRH) agonist for
3 months, from post-menopausal women, from pregnant women and in myometrium from
women without fibroid disease. Women with menstrual periods were classified
according to the phase of the cycle. In tissues from non-treated premenopausal
women, IGF-I mRNA expression was significantly higher in fibroids than in
myometrium, with no differences related to phase of the menstrual cycle. In post
menopausal women and in GnRH agonist-treated women responding to treatment,
similar mRNA expression was seen in myometrium and fibroids but the
concentrations were lower than in untreated premenopausal women. The IGF-I mRNA
value in fibroids from pregnant women was higher than in any other group and
myometrium from pregnant women exhibited higher mRNA expression than myometrium
from non-treated premenopausal women. The IGF-I protein was more abundant in
fibroids than in myometrium of non-treated premenopausal and of pregnant women
and in both tissues the concentration was significantly higher in the group of
pregnant women. The IGF-I protein concentrations in fibroids and myometrium from
GnRH agonist-treated and post-menopausal women were similar to those from
premenopausal non-treated women. High sex steroid concentrations in pregnant and
non-pregnant women of fertile age seem to be associated with a higher expression
of IGF-I in fibroids than in myometrium, suggesting that IGF-I contributes to the
selective growth advantage of these tumours.
PMID- 11006321
TI - Differential expression of the alpha(2)-macroglobulin receptor and the receptor
associated protein in normal human endometrium and endometrial carcinoma.
AB - Extracellular matrix degradation, mediated by the activation of receptor-bound
proteolytic enzymes, is essential to the process of cellular invasion. Many
normal physiological functions such as endometrial remodelling are reliant on the
activation of these surface associated proteolytic enzymes, as are pathological
functions such as cancer-cell invasion. The internalization of proteolytic
complexes is mediated by the multi-functional clearance receptor, alpha(2)
macroglobulin receptor/LRP. The role of LRP and its ligand binding inhibitor, the
receptor-associated protein (RAP), in the advancement of invasive endometrial
carcinoma is unknown. The aim of this study was to compare the expression of LRP
and RAP mRNA in normal endometrium (n = 14) and endometrial carcinoma (n = 33) by
semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).
Expression of LRP mRNA in normal endometrium was significantly increased in the
secretory phase when compared with proliferative phase endometrium (P: < 0.05).
The expression of LRP in all carcinomas examined was significantly reduced to
about 20% of the amount in normal endometrium (P: < 0.05), whereas RAP expression
was not significantly different between endometrium and carcinoma. No significant
difference in the level of LRP or RAP expression was observed between carcinoma
grades or stages. In conclusion, we have shown that LRP expression is
differentially regulated in the normal endometrium during the menstrual cycle and
is decreased in invasive endometrial carcinomas.
PMID- 11006322
TI - Increased concentrations of soluble tumour necrosis factor receptor (sTNFR) I and
II in peritoneal fluid from women with endometriosis.
AB - Tumour necrosis factor alpha (TNFalpha), a proapoptotic cytokine, is known to be
present in peritoneal fluid from women with endometriosis. An emerging view is
that soluble TNF receptors (sTNFR) can modulate the effects of TNFalpha by acting
as TNFalpha antagonists. To assess the relevance of sTNFRs in the pathophysiology
of endometriosis, concentrations of sTNFR I, sTNFR II and TNFalpha in peritoneal
fluid from women with endometriosis (n = 53) and without endometriosis (n = 40)
were measured. Concentrations of both sTNFR I and sTNFR II in peritoneal fluid
from women with endometriosis were significantly higher than in peritoneal fluid
from women without endometriosis, both in the follicular and the luteal phases.
TNFalpha concentrations did not differ in patients with and without endometriosis
in both phases. When stratified by the stage of the disease, women with both
stages I/II and stages III/IV exhibited significantly higher concentrations of
sTNFR I and sTNFR II in peritoneal fluid, compared with women without
endometriosis, whereas no appreciable difference in the concentrations was
detected between stages I/II and stages III/IV. A significant correlation was
found between the concentrations of sTNFR I and sTNFR II; while the correlations
between TNFalpha and sTNFR I or sTNFR II, were either not significant or were
very weak. Furthermore, mRNA for the membrane-associated TNF receptor type 1 and
TNF receptor type 2, both of which convey the effects of TNFalpha, were shown to
be expressed in endometriotic tissues as well as eutopic endometrium. Together,
these findings suggest a possible involvement of sTNFRs in the pathophysiology of
endometriosis.
PMID- 11006323
TI - Expression of vascular endothelial growth factor (VEGF) and placental growth
factor (PlGF) in conceptus and endometrium during implantation in the rhesus
monkey.
AB - The aim of this study was to analyse the expression of transcripts and proteins
for vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF)
in different compartments of the early conceptus at primary implantation sites
during lacunar (n = 6), early villous (n = 9) and villous placenta (n = 6) stages
of gestation in the rhesus monkey. During the lacunar stage, VEGF expression was
observed in the cytotrophoblast cells lining the extraembryonic cavity, but these
cells did not express PlGF. With further development, cytotrophoblast cells
lining villi, forming columns, and constituting anchoring villi, expressed both
VEGF and PlGF during early villous and villous placenta stages. In addition,
chorion, amnion and villous stromal cells expressed both VEGF and PlGF proteins
and mRNA. During the lacunar stage, all epithelial cells in maternal endometrium
generally expressed VEGF, while PlGF expression was observed in the plaque
epithelium only. As gestation advanced, the expression of VEGF and PlGF from
plaque cells decreased, and in surface and glandular epithelium the expression of
VEGF increased, while the expression of PlGF remained unaltered. Decidual stromal
cells expressed VEGF and PlGF only at low levels during the lacunar stage, while
the expression of both increased during the early villous and the villous
placenta stages of implantation. It appears from the present study that the
expression of VEGF and PlGF are regulated in a temporal and spatial manner during
early stages of implantation and that their concerted actions in placental and
maternal compartments play a critical role in the evolving pregnancy in the
rhesus monkey.
PMID- 11006324
TI - Localization of E-cadherin in villous, extravillous and vascular trophoblasts
during intrauterine, ectopic and molar pregnancy.
AB - Previous reports have described down-regulation of E-cadherin in trophoblasts
differentiating to an invasive phenotype. This study shows the localization of E
cadherin in a prospective design with stereological sampling of fetal and
maternal first, second and third trimester tissue. E-cadherin was observed in
villous cytotrophoblasts, and in non-proliferating, intermediate trophoblasts
(IT) within cell columns and islands in intrauterine, ectopic and partial molar
placentas. Highly proliferating IT with cytological atypia in complete molar
placentas were also E-cadherin-positive. E-cadherin was present in trophoblasts
throughout the anchoring cell columns. Trophoblasts undergoing epithelial
mesenchymal transformation (EMT) detaching from the distal cell columns and
deeper located single extravillous interstitial trophoblasts (EVT) showed E
cadherin-negative breaches in the cell membrane. Prior to the late second
trimester, the relative number of E-cadherin-positive single EMT and EVT differed
from the total number of cytokeratin-positive trophoblasts. Intraluminal,
endovascular and perivascular trophoblasts adjacent to the maternal vessels were
also E-cadherin-positive, but a highly varying pattern was observed at different
ages of gestation. Our results indicate a temporary shift in E-cadherin
expression in extravillous trophoblasts possessing a migrating and invasive
potential. Functional E-cadherin may be restored as trophoblasts aggregate in the
decidua and the vessel wall after completion of migration.
PMID- 11006325
TI - Leptin modulates extracellular matrix molecules and metalloproteinases: possible
implications for trophoblast invasion.
AB - Leptin is a circulating hormone which plays an important role in the regulation
of energy balance, haemopoiesis and reproduction. Leptin and its receptor (leptin
R) are localized in human placental tissue but their function is not known. In
this study we have investigated the expression of leptin and leptin-R in the
human placenta with particular attention to extravillous cytotrophoblastic cell
islands and cell columns which play a pivotal role in trophoblast invasion and
placental growth. We demonstrate that leptin-R immunoreactivity shows a strong
expression in the distal extravillous cytotrophoblastic cells of cell columns
invading the basal plate, whereas leptin expression is homogeneously expressed in
all the cellular components of cell columns. Since the invasive ability of the
distally located extravillous cytotrophoblast of cell columns is known to be
regulated by a variety of proteases and some extracellular matrix molecules, we
tested the influence of leptin on the in-vitro production of matrix
metalloproteinase (MMP)-2, MMP-9 and fetal fibronectin (fFN) by cytotrophoblastic
cells. We demonstrate that leptin increases, in a dose-dependent manner, the
secretion of immunoreactive MMP-2 and fFN and enhances the activity of MMP-9 in
cultured cytotrophoblastic cells. Our results suggest that leptin and leptin-R
could have a role in the invasive processes of the extravillous cytotrophoblastic
cells by modulating the expression of MMPs. In addition, these results provide a
foundation for studying pathological conditions characterized by insufficient or
excessive trophoblast invasion.
PMID- 11006326
TI - Local fetal signal is not required for maintaining IGFBP gene expression in the
human decidua: evidence from extrauterine pregnancies.
AB - Insulin-like growth factor-II (IGF-II) from the invading extravillous
cytotrophoblasts (EVTs) and insulin-like growth factor binding proteins (IGFBPs)
from the maternal decidua interact at the feto-maternal interface and regulate
implantation and placentation. To determine whether a local stimulus from the
fetus is important in the regulation of IGFBP gene expression in the human
decidua, we compared the expression of IGFBP genes in intra- and extrauterine
(tubal) pregnancies. The expression of IGF-II and IGFBP-1 to IGFBP-6 mRNAs was
determined by in-situ hybridization in the Fallopian tubes of extrauterine
pregnancies and concurrent decidua (n = 6), and in the placentae and Fallopian
tubes of intrauterine pregnancies (n = 6). All six IGFBP mRNAs were identified in
the decidualized endometrium and decidualized Fallopian tubes of intra- and
extrauterine pregnancies, with IGFBP-1 mRNA being the predominant mRNA. IGFBP-4
was the second most predominant mRNA and was slightly more abundant in the
decidua of extrauterine pregnancies than of intrauterine pregnancies. IGF-II mRNA
was expressed mainly in cells of fetal origin. The fact that the IGFBP mRNAs were
expressed similarly in both intra- and extrauterine pregnancies indicates that
the local physical stimulus from an implanting fetus is not necessary to induce
or maintain decidual IGFBP gene expression.
PMID- 11006327
TI - Plant PtdIns 3-kinase goes nuclear.
PMID- 11006328
TI - Cell biology of plant and fungal tip growth--getting to the point.
PMID- 11006329
TI - Comparative genomics of plant chromosomes.
PMID- 11006330
TI - Overexpression of a gene encoding a cytochrome P450, CYP78A9, induces large and
seedless fruit in arabidopsis.
AB - An activation tagging screen in which the cauliflower mosaic virus 35S enhancer
was inserted randomly into an Arabidopsis genome homozygous for the floral
homeotic mutation apetala2-1 (ap2-1) resulted in a line (28-5) with
extraordinarily wide, heart-shaped ovaries. The ovary of the 28-5 ap2-1 mutant
shows an oval shape because of increased numbers of enlarged cells. When the ap2
1 mutation is crossed out of the genetic background, more elongated rather than
wider fruits are obtained. Normally, Arabidopsis fruits will develop to a normal
size only when the ovules are present and fertilized. In the 28-5 single mutant,
the siliques keep growing despite failure of fertilization and can reach nearly
normal size. When wild-type pollen was used to pollinate the mutant pistil, the
pollinated 28-5 silique became >10% longer and 40% wider than a wild-type
silique, although producing very few seeds. The enhancer insertion in line 28-5
acts by hyperactivating a cytochrome P450 gene, CYP78A9. The pistil of 28-5 ap2-1
mutant flowers shows a structure similar to that of Capsella bursa-pastoris, a
distant mustard relative of Arabidopsis, suggesting that the processes regulated
by the CYP78A9-encoded protein may be involved in evolutionary control of carpel
shape.
PMID- 11006331
TI - Phenotypic instability and rapid gene silencing in newly formed arabidopsis
allotetraploids.
AB - Allopolyploid hybridization serves as a major pathway for plant evolution, but in
its early stages it is associated with phenotypic and genomic instabilities that
are poorly understood. We have investigated allopolyploidization between
Arabidopsis thaliana (2n = 2x = 10; n, gametic chromosome number; x, haploid
chromosome number) and Cardaminopsis arenosa (2n = 4x = 32). The variable
phenotype of the allotetraploids could not be explained by cytological
abnormalities. However, we found suppression of 20 of the 700 genes examined by
amplified fragment length polymorphism of cDNA. Independent reverse transcription
polymerase chain reaction analyses of 10 of these 20 genes confirmed silencing in
three of them, suggesting that approximately 0.4% of the genes in the
allotetraploids are silenced. These three silenced genes were characterized. One,
called K7, is repeated and similar to transposons. Another is RAP2.1, a member of
the large APETALA2 (AP2) gene family, and has a repeated element upstream of its
5' end. The last, L6, is an unknown gene close to ALCOHOL DEHYDROGENASE on
chromosome 1. CNG DNA methylation of K7 was less in the allotetraploids than in
the parents, and the element varied in copy number. That K7 could be reactivated
suggests epigenetic regulation. L6 was methylated in the C. arenosa genome. The
present evidence that gene silencing accompanies allopolyploidization opens new
avenues to this area of research.
PMID- 11006332
TI - UV radiation-sensitive norin 1 rice contains defective cyclobutane pyrimidine
dimer photolyase.
AB - Norin 1, a progenitor of many economically important Japanese rice strains, is
highly sensitive to the damaging effects of UVB radiation (wavelengths 290 to 320
nm). Norin 1 seedlings are deficient in photorepair of cyclobutane pyrimidine
dimers. However, the molecular origin of this deficiency was not known and,
because rice photolyase genes have not been cloned and sequenced, could not be
determined by examining photolyase structural genes or upstream regulatory
elements for mutations. We therefore used a photoflash approach, which showed
that the deficiency in photorepair in vivo resulted from a functionally altered
photolyase. These results were confirmed by studies with extracts, which showed
that the Norin 1 photolyase-dimer complex was highly thermolabile relative to the
wild-type Sasanishiki photolyase. This deficiency results from a
structure/function alteration of photolyase rather than of nonspecific repair,
photolytic, or regulatory elements. Thus, the molecular origin of this plant DNA
repair deficiency, resulting from a spontaneously occurring mutation to UV
radiation sensitivity, is defective photolyase.
PMID- 11006333
TI - A GAL4-like protein is involved in the switch between biotrophic and necrotrophic
phases of the infection process of Colletotrichum lindemuthianum on common bean.
.
AB - Random insertional mutagenesis was conducted with the hemibiotrophic fungus
Colletotrichum lindemuthianum, causal agent of common bean anthracnose. Nine
mutants that were altered in their infection process on the host plant were
generated. One of these, H433 is a nonpathogenic mutant able to induce necrotic
spots on infected leaves rapidly. These spots are similar to those observed
during the hypersensitive reaction. Cytological observations showed that the
development of the mutant H433 is stopped at the switch between the biotrophic
and the necrotrophic phases. This mutant carries two independent insertions of
the transforming plasmid pAN7-1. Complementation studies using the wild-type
genomic regions corresponding to the two insertions showed that one is
responsible for the H433 phenotype. Sequencing analysis identified a single open
reading frame that encoded a putative transcriptional activator belonging to the
fungal zinc cluster (Zn[II](2)Cys(6)) family. The corresponding gene was
designated CLTA1 (for C. lindemuthianum transcriptional activator 1). Expression
studies showed that CLTA1 is expressed in low amounts during in vitro culture.
Targeted disrupted strains were generated, and they exhibited the same phenotype
as the original mutant H433. Complementation of these disrupted strains by the
CLTA1 gene led to full restoration of pathogenicity. This study demonstrates that
CLTA1 is both a pathogenicity gene and a regulatory gene involved in the switch
between biotrophy and necrotrophy of the infection process of a hemibiotrophic
fungus.
PMID- 11006334
TI - Loss of function of a rice brassinosteroid insensitive1 homolog prevents
internode elongation and bending of the lamina joint.
AB - Brassinosteroids (BRs) are plant growth-promoting natural products required for
plant growth and development. Physiological studies have demonstrated that
exogenous BR, alone or in combination with auxin, enhance bending of the lamina
joint of rice. However, little is known about the function of endogenous BR in
rice or other grass species. We report here the phenotypical and molecular
characterization of a rice dwarf mutant, d61, that is less sensitive to BR
compared to the wild type. We cloned a rice gene, OsBRI1, with extensive sequence
similarity to that of the Arabidopsis BRI gene, which encodes a putative BR
receptor kinase. Linkage analysis showed that the OsBRI1 gene is closely linked
to the d61 locus. Single nucleotide substitutions found at different sites of the
d61 alleles would give rise to amino acid changes in the corresponding
polypeptides. Furthermore, introduction of the entire OsBRI1 coding region,
including the 5' and 3' flanking sequences, into d61 plants complemented the
mutation to display the wild-type phenotype. Transgenic plants carrying the
antisense strand of the OsBRI1 transcript showed similar or even more severe
phenotypes than those of the d61 mutants. Our results show that OsBRI1 functions
in various growth and developmental processes in rice, including (1) internode
elongation, by inducing the formation of the intercalary meristem and the
longitudinal elongation of internode cells; (2) bending of the lamina joint; and
(3) skotomorphogenesis.
PMID- 11006335
TI - Regulation of SUP expression identifies multiple regulators involved in
arabidopsis floral meristem development.
AB - During the course of flower development, floral homeotic genes are expressed in
defined concentric regions of floral meristems called whorls. The SUPERMAN (SUP,
also called FLO10) gene, which encodes a C2H2-type zinc finger protein, is
involved in maintenance of the stamen/carpel whorl boundary (the boundary between
whorl 3 and whorl 4) in Arabidopsis. Here, we show that the regulation of SUP
expression in floral meristems is complex, consisting of two distinct phases,
initiation and maintenance. The floral meristem identity gene LEAFY (LFY) plays a
role in the initiation phase through at least two pathways, which differ from
each other in the involvement of two homeotic genes, APETALA3 (AP3) and
PISTILLATA (PI). AP3, PI, and another homeotic gene, AGAMOUS (AG), are further
required for SUP expression in the later maintenance phase. Aside from these
genes, there are other as yet unidentified genes that control both the temporal
and spatial patterns of SUP expression in whorl 3 floral meristems. SUP appears
to act transiently, probably functioning to trigger a genetic circuit that
creates the correct position of the whorl 3/whorl 4 boundary.
PMID- 11006336
TI - anthocyanin1 of petunia encodes a basic helix-loop-helix protein that directly
activates transcription of structural anthocyanin genes.
AB - The petunia loci anthocyanin1 (an1), an2, an4, and an11 are required for the
transcription of anthocyanin biosynthetic genes in floral organs. The an2 and
an11 loci were recently cloned and shown to encode a MYB-domain transcriptional
activator and a cytosolic WD40 protein, respectively. Here, we report the
isolation of an1 by transposon tagging. an1 encodes a new member of the basic
helix-loop-helix family of transcription factors that is functionally and
evolutionarily distinct from JAF13, the apparent petunia ortholog of maize RED1
and snapdragon DELILA. We provide genetic evidence that the transcription factors
encoded by an1, an2, and an4 operate in an unexpectedly complex regulatory
hierarchy. In leaves, ectopic expression of AN2 induces an1 expression, whereas
in anthers, an1 expression depends on an4, encoding (or controlling) a MYB
protein that is paralogous to AN2. Experiments with transgenic plants expressing
a post-translationally controlled AN1-GLUCOCORTICOID RECEPTOR fusion protein
indicated that independent of protein synthesis, AN1 directly activates the
expression of the dfrA gene encoding the enzyme dihydroflavonol 4-reductase and
of Pmyb27 encoding a MYB-domain protein of unknown function.
PMID- 11006337
TI - Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.
AB - Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic
acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses
to both abiotic and biotic stress factors. Earlier studies demonstrated that
ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death
pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA
and JA signaling in influencing O(3)-induced cell death. Expression of salicylate
hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me
JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA
concentrations and completely abolished O(3)-induced cell death. Cvi-0
synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited
much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of
the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic
relationship between JA- and SA-signaling pathways in controlling the magnitude
of O(3)-induced HR-like cell death.
PMID- 11006338
TI - Four genes of Medicago truncatula controlling components of a nod factor
transduction pathway.
AB - Rhizobium nodulation (Nod) factors are lipo-chitooligosaccharides that act as
symbiotic signals, eliciting several key developmental responses in the roots of
legume hosts. Using nodulation-defective mutants of Medicago truncatula, we have
started to dissect the genetic control of Nod factor transduction. Mutants in
four genes (DMI1, DMI2, DMI3, and NSP) were pleiotropically affected in Nod
factor responses, indicating that these genes are required for a Nod factor
activated signal transduction pathway that leads to symbiotic responses such as
root hair deformations, expressions of nodulin genes, and cortical cell
divisions. Mutant analysis also provides evidence that Nod factors have a dual
effect on the growth of root hair: inhibition of endogenous (plant) tip growth,
and elicitation of a novel tip growth dependent on (bacterial) Nod factors. dmi1,
dmi2, and dmi3 mutants are also unable to establish a symbiotic association with
endomycorrhizal fungi, indicating that there are at least three common steps to
nodulation and endomycorrhization in M. truncatula and providing further evidence
for a common signaling pathway between nodulation and mycorrhization.
PMID- 11006339
TI - SOS3 function in plant salt tolerance requires N-myristoylation and calcium
binding.
AB - The salt tolerance gene SOS3 (for salt overly sensitive3) of Arabidopsis is
predicted to encode a calcium binding protein with an N-myristoylation signature
sequence. Here, we examine the myristoylation and calcium binding properties of
SOS3 and their functional significance in plant tolerance to salt. Treatment of
young Arabidopsis seedlings with the myristoylation inhibitor 2-hydroxymyristic
acid caused the swelling of root tips, mimicking the phenotype of the salt
hypersensitive mutant sos3-1. In vitro translation assays with reticulocyte
showed that the SOS3 protein was myristoylated. Targeted mutagenesis of the N
terminal glycine-2 to alanine prevented the myristoylation of SOS3. The
functional significance of SOS3 myristoylation was examined by expressing the
wild-type myristoylated SOS3 and the mutated nonmyristoylated SOS3 in the sos3-1
mutant. Expression of the myristoylated but not the nonmyristoylated SOS3
complemented the salt-hypersensitive phenotype of sos3-1 plants. No significant
difference in membrane association was observed between the myristoylated and
nonmyristoylated SOS3. Gel mobility shift and (45)Ca(2)+ overlay assays
demonstrated that SOS3 is a unique calcium binding protein and that the sos3-1
mutation substantially reduced the capacity of SOS3 to bind calcium. The
resulting mutant SOS3 protein was not able to interact with the SOS2 protein
kinase and was less capable of activating it. Together, these results strongly
suggest that both N-myristoylation and calcium binding are required for SOS3
function in plant salt tolerance.
PMID- 11006340
TI - Association of phosphatidylinositol 3-kinase with nuclear transcription sites in
higher plants.
AB - The kinases responsible for phosphorylation of inositol-containing lipids are
essential for many aspects of normal eukaryotic cell function. Genetic and
biochemical studies have established that the phosphatidylinositol (PtdIns) 3
kinase encoded by the yeast VPS34 gene is essential for the efficient sorting and
delivery of proteins to the vacuole; the kinase encoded by the human VPS34
homolog has been equally implicated in the control of intracellular vesicle
traffic. The plant VPS34 homolog also is required for normal growth and
development, and although a role for PtdIns 3-kinase in vesicle trafficking is
likely, it has not been established. In this study, we have shown that
considerable PtdIns 3-kinase activity is associated with the internal matrix of
nuclei isolated from carrot suspension cells. Immunocytochemical and confocal
laser scanning microscopy studies using the monoclonal antibody JIM135 (John
Innes Monoclonal 135), raised against a truncated version of the soybean PtdIns 3
kinase, SPI3K-5p, revealed that this kinase appears to have a distinct and
punctate distribution within the plant nucleus and nucleolus. Dual probing of
root sections with JIM135 and anti-bromo-UTP antibodies, after in vitro
transcription had been allowed to proceed in the presence of bromo-UTP, showed
that SPI3K-5p associates with active nuclear and nucleolar transcription sites.
These findings suggest a possible link between PtdIns 3-kinase activity and
nuclear transcription in plants.
PMID- 11006341
TI - Genetic manipulation of isoflavone 7-O-methyltransferase enhances biosynthesis of
4'-O-methylated isoflavonoid phytoalexins and disease resistance in alfalfa.
AB - 4'-O-Methylation of an isoflavonoid intermediate is a key reaction in the
biosynthesis of the phytoalexin medicarpin in legumes. However, isoflavone O
methyltransferase (IOMT) from alfalfa converts the isoflavone daidzein to 7-O
methyl daidzein (isoformononetin) in vitro as well as in vivo in unchallenged
leaves of transgenic alfalfa ectopically expressing IOMT. In contrast,
elicitation of IOMT-overexpressing plants with CuCl(2) or infecting these plants
with Phoma medicaginis leads to greater accumulation of formononetin (4'-O-methyl
daidzein) and medicarpin in the leaves than does elicitation or infection of
control plants, and no isoformononetin is detected. Overexpression of IOMT
results in increased induction of phenylpropanoid/isoflavonoid pathway gene
transcripts after infection but has little effect on basal expression of these
genes. IOMT-overexpressing plants display resistance to P. medicaginis. The
apparently different regiospecificities of IOMT in vivo and in vitro are
discussed in relation to potential metabolic channeling at the entry point into
the isoflavonoid pathway.
PMID- 11006342
TI - MAP kinase and protein kinase A-dependent mobilization of triacylglycerol and
glycogen during appressorium turgor generation by Magnaporthe grisea.
AB - Magnaporthe grisea produces an infection structure called an appressorium, which
is used to breach the plant cuticle by mechanical force. Appressoria generate
hydrostatic turgor by accumulating molar concentrations of glycerol. To
investigate the genetic control and biochemical mechanism for turgor generation,
we assayed glycerol biosynthetic enzymes during appressorium development, and the
movement of storage reserves was monitored in developmental mutants. Enzymatic
activities for glycerol generation from carbohydrate sources were present in
appressoria but did not increase during development. In contrast, triacylglycerol
lipase activity increased during appressorium maturation. Rapid glycogen
degradation occurred during conidial germination, followed by accumulation in
incipient appressoria and dissolution before turgor generation. Lipid droplets
also moved to the incipient appressorium and coalesced into a central vacuole
before degrading at the onset of turgor generation. Glycogen and lipid
mobilization did not occur in a Deltapmk1 mutant, which lacked the mitogen
activated protein kinase (MAPK) required for appressorium differentiation, and
was retarded markedly in a DeltacpkA mutant, which lacks the catalytic subunit of
cAMP-dependent protein kinase A (PKA). Glycogen and lipid degradation were very
rapid in a Deltamac1 sum1-99 mutant, which carries a mutation in the regulatory
subunit of PKA, occurring before appressorium morphogenesis was complete. Mass
transfer of storage carbohydrate and lipid reserves to the appressorium therefore
occurs under control of the PMK1 MAPK pathway. Turgor generation then proceeds by
compartmentalization and rapid degradation of lipid and glycogen reserves under
control of the CPKA/SUM1-encoded PKA holoenzyme.
PMID- 11006343
TI - Identification and characterization of a novel microtubule-based motor associated
with membranous organelles in tobacco pollen tubes.
AB - Pollen tube growth depends on the differential distribution of organelles and
vesicles along the tube. The role of microtubules in organelle movement is
uncertain, mainly because information at the molecular level is limited. In an
effort to understand the molecular basis of microtubule-based movement, we
isolated from tobacco pollen tubes polypeptides that cosediment with microtubules
in an ATP-dependent manner. Major polypeptides released from microtubules by ATP
(ATP-MAPs) had molecular masses of 90, 80, and 41 kD. Several findings indicate
that the 90-kD ATP-MAP is a kinesin-related motor: binding of the polypeptide to
microtubules was enhanced by the nonhydrolyzable ATP analog AMP-PNP; the 90-kD
polypeptide reacted specifically with a peptide antibody directed against a
highly conserved region in the motor domain of the kinesin superfamily; purified
90-kD ATP-MAP induced microtubules to glide in motility assays in vitro; and the
90-kD ATP-MAP cofractionated with microtubule-activated ATPase activity.
Immunolocalization studies indicated that the 90-kD ATP-MAP binds to organelles
associated with microtubules in the cortical region of the pollen tube. These
findings suggest that the 90-kD ATP-MAP is a kinesin-related microtubule motor
that moves organelles in the cortex of growing pollen tubes.
PMID- 11006344
TI - A lily stylar pectin is necessary for pollen tube adhesion to an in vitro stylar
matrix.
AB - Pollen tube cells adhere to the wall surface of the stylar transmitting tract
epidermis in lily. This adhesion has been proposed as essential for the proper
delivery of the sperm cells to the ovule. An in vitro adhesion bioassay has been
used to isolate two stylar molecules required for lily pollen tube adhesion. The
first molecule was determined to be a small, cysteine-rich protein with some
sequence similarity to lipid transfer proteins and now called stigma/stylar
cysteine-rich adhesin (SCA). The second, larger, molecule has now been purified
from style fragments and characterized. Chemical composition, specific enzyme
degradations, and immunolabeling data support the idea that this molecule
required for pollen tube adhesion is a pectic polysaccharide. In vitro binding
assays revealed that this lily stylar adhesive pectin and SCA are able to bind to
each other in a pH-dependent manner.
PMID- 11006345
TI - The classical arabinogalactan protein gene family of arabidopsis.
AB - Arabinogalactan proteins (AGPs) are extracellular proteoglycans implicated in
plant growth and development. We searched for classical AGPs in Arabidopsis by
identifying expressed sequence tags based on the conserved domain structure of
the predicted protein backbone. To confirm that these genes encoded bona fide
AGPs, we purified native AGPs and then deglycosylated and deblocked them for N
terminal protein sequencing. In total, we identified 15 genes encoding the
protein backbones of classical AGPs, including genes for AG peptides-AGPs with
very short backbones (10 to 13 amino acid residues). Seven of the AGPs were
verified as AGPs by protein sequencing. A gene encoding a putative cell adhesion
molecule with AGP-like domains was also identified. This work provides a firm
foundation for beginning functional analysis by using a genetic approach.
PMID- 11006346
TI - Biogenesis of the chloroplast-encoded D1 protein: regulation of translation
elongation, insertion, and assembly into photosystem II.
AB - Regulation of translation elongation, membrane insertion, and assembly of the
chloroplast-encoded D1 protein of photosystem II (PSII) was studied using a
chloroplast translation system in organello. Translation elongation of D1 protein
was found to be regulated by (1) a redox component that can be activated not only
by photosynthetic electron transfer but also by reduction with DTT; (2) the trans
thylakoid proton gradient, which is absolutely required for elongation of D1
nascent chains on the thylakoid membrane; and (3) the thiol reactants N
ethylmaleimide (NEM) and iodosobenzoic acid (IBZ), which inhibit translation
elongation with concomitant accumulation of distinct D1 pausing intermediates.
These results demonstrate that D1 translation elongation and membrane insertion
are tightly coupled and highly regulated processes in that proper insertion is a
prerequisite for translation elongation of D1. Cotranslational and post
translational assembly steps of D1 into PSII reaction center and core complexes
occurred independently of photosynthetic electron transfer or trans-thylakoid
proton gradient but were strongly affected by the thiol reactants DTT, NEM, and
IBZ. These compounds reduced the stability of the early PSII assembly
intermediates, hampered the C-terminal processing of the precursor of D1, and
prevented the post-translational reassociation of CP43, indicating a strong
dependence of the D1 assembly steps on proper redox conditions and the formation
of disulfide bonds.
PMID- 11006348
TI - PPAR-alpha: a key to the mechanism of hepatoprotection by clofibrate.
AB - The article highlighted in this issue is "Peroxisome Proliferator-Activated
Receptor Alpha-Null Mice Lack Resistance to Acetaminophen Hepatotoxicity
Following Clofibrate Exposure" by Chuan Chen, Gayle E. Hennig, Herbert E.
Whiteley, J Christopher Corton, and Jose E. Manautou (pp. 338-344).
PMID- 11006347
TI - The bacterial elicitor flagellin activates its receptor in tomato cells according
to the address-message concept.
AB - flg22, a peptide corresponding to the most conserved domain of bacterial
flagellin, acts as a potent elicitor in plants. Here, we have used an iodinated
derivative of flg22 ((125)I-labeled Tyr-flg22) as a molecular probe for the
flagellin receptor in tomato cells. This radioligand showed rapid binding to a
single class of specific, saturable, high-affinity receptor sites in intact cells
and membrane preparations. Binding, although essentially nonreversible under
physiological conditions, was not covalent, and chemical cross-linking was
required to specifically label a single polypeptide of 115 kD. Intact flagellin
and elicitor-active flagellin peptides but not biologically inactive analogs
efficiently competed for binding of radioligand. Peptides lacking the C terminus
of the conserved domain, previously found to act as competitive antagonists of
elicitor action in tomato cells, also competed for binding of radioligand. Thus,
this novel, high-affinity binding site exhibited all the characteristics expected
of a functional receptor of bacterial flagellin. For a model of receptor
activation, we propose a two-step mechanism according to the address-message
concept, in which binding of the N terminus (address) is the first step and
activation of responses with the C terminus (message) is the second step.
PMID- 11006349
TI - Sheldon D. Murphy.
PMID- 11006350
TI - Symposium overview: mechanism of action of nicotine on neuronal acetylcholine
receptors, from molecule to behavior.
AB - Nicotine has long been known to interact with nicotinic acetylcholine (ACh)
receptors since Langley used it extensively to chart sympathetic ganglia a
century ago. It has also been used as an effective insecticide. However, it was
not until the 1990s that the significance of nicotine was increasingly recognized
from the toxicological, pharmacological, and environmental points of view. This
is partly because studies of neuronal nicotinic ACh receptors are rapidly
emerging from orphan status, fueled by several lines of research. Since
Alzheimer's disease is known to be associated with down-regulation of cholinergic
activity in the brain, a variety of nicotine derivatives are being tested and
developed for treatment of the disease. Public awareness of the adverse effects
of nicotine has reached the highest level recently. Since insect resistance to
insecticides is one of the most serious issues in the pest-control arena, it is
an urgent requirement to develop new insecticides that act on target sites not
shared by the existing insecticides. The neuronal nicotinic ACh receptor is one
of them, and new nicotinoids are being developed. Thus, the time is ripe to
discuss the mechanism of action of nicotine from a variety of angles, including
the molecular, physiological, and behavioral points of view. This Symposium
covered a wide area of nicotine studies: genetic, genomic, and functional aspects
of nicotinic ACh receptors were studied, as related to anthelmintics and
insecticides; interactions between ethanol and nicotine out the ACh receptor were
analyzed, in an attempt to explain the well-known heavy drinker-heavy smoker
correlation; the mechanisms that underlie the desensitization of ACh receptors
were studied as related to nicotine action; selective pharmacological profiles of
nicotine, and descriptions of some derivatives were described; and chronic
nicotine infusion effects on memory were examined using animal models.
PMID- 11006351
TI - Quantification of DNA adducts formed in liver, lungs, and isolated lung cells of
rats and mice exposed to (14)C-styrene by nose-only inhalation.
AB - Bronchiolo-alveolar tumors were observed in mice exposed chronically to 160 ppm
styrene, whereas no tumors were seen in rats up to concentrations of 1000 ppm.
Clara cells, which are predominant in the bronchiolo-alveolar region in mouse
lungs but less numerous in rat and human lung, contain various cytochrome P450s,
which may oxidize styrene to the rodent carcinogen styrene-7,8-oxide (SO) and
other reactive metabolites. Reactive metabolites may form specific DNA adducts
and induce the tumors observed in mice. To determine DNA adducts in specific
tissues and cell types, rats and mice were exposed to 160 ppm [ring-U
(14)C]styrene by nose-only inhalation for 6 h in a recirculating exposure system.
Liver and lungs were isolated 0 and 42 h after exposure. Fractions enriched in
Type II cells and Clara cells were isolated from rat and mouse lung,
respectively. DNA adduct profiles differed quantitatively and qualitatively in
liver, total lung, and enriched lung cell fractions. At 0 and 42 h after
exposure, the two isomeric N:7-guanine adducts of SO (measured together, HPEG)
were present in liver at 3.0 +/- 0.2 and 1.9 +/- 0.3 (rat) and 1.2 +/- 0.2 and
3.2 +/- 0.5 (mouse) per 10(8) bases. Several other, unidentified adducts were
present at two to three times higher concentrations in mouse, but not in rat
liver. In both rat and mouse lung, HPEG was the major adduct at approximately 1
per 10(8) bases at 0 h, and these levels halved at 42 h. In both rat Type II and
non-Type II cells, HPEG was the major adduct and was about three times higher in
Type II cells than in total lung. For mice, DNA adduct levels in Clara cells and
non-Clara cells were similar to total lung. The hepatic covalent binding index
(CBI) at 0 and 42 h was 0.19 +/- 0.06 and 0.14 +/- 0.03 (rat) and 0. 25 +/- 0.11
and 0.44 +/- 0.23 (mouse), respectively. The pulmonary CBIs, based on tissues
combined for 0 and 42 h, were 0.17 +/- 0.04 (rat) and 0.24 +/- 0.04 (mouse).
Compared with CBIs for other genotoxicants, these values indicate that styrene
has only very weak adduct-forming potency. The overall results of this study
indicate that DNA adduct formation does not play an important role in styrene
tumorigenicity in chronically exposed mice.
PMID- 11006352
TI - Influence of beta-naphthoflavone on 7,12-dimethylbenz(a)anthracene metabolism,
DNA adduction, and tumorigenicity in rainbow trout.
AB - Metabolism, DNA adduction, and tumor induction by 7, 12-dimethylbenz(a)anthracene
(DMBA) were examined in cultured trout liver cells and in vivo in trout.
Modulating CYP1A1 activity indicated this enzyme plays a significant role in
metabolizing DMBA to water-soluble compounds in isolated trout liver cells. The
major DMBA metabolites identified in trout liver cells were 10-, 11-, 8,9-, and
5,6-DMBA dihydrodiols, and DMBA, 2- or 3- or 4-phenol; 7-OH-methyl-12-methyl
benz(a)anthracene and 12-OH-methyl-7-methyl-benz(a)anthracene were minor
metabolites. A very small amount of DMBA-3,4-dihydrodiol was detected, and polar
metabolites, which did not migrate with any DMBA metabolite standards, were
observed. Incubating trout hepatocytes with DMBA-3, 4-dihydrodiol produced three
prominent, nonpolar adducts indistinguishable from those in mouse embryo cells.
However, DMBA-DNA adducts, formed in trout in vivo or in trout liver cells
exposed to DMBA, were predominantly more polar than those formed in mouse embryo
fibroblasts, and levels of DMBA-DNA adducts formed in trout liver cells were not
significantly altered by modulating CYP1A1 activity. No significant repair of
DMBA-DNA adducts was detected in cultured trout liver cells over a 48-h period,
supporting previous studies indicating that fish are less efficient than mammals
in repairing polyaromatic hydrocarbon DNA adducts. Compared to animals receiving
DMBA alone, beta-naphthoflavone pretreatment in vivo did not affect hepatic
CYP1A1, DMBA-DNA adducts, nor hepatic tumor response; but did significantly
reduce tumor response in two other target organs. These results collectively
indicate that DMBA bioactivation to DNA-binding metabolites in trout liver cells
and mouse embryo cells predominantly involve different metabolic pathways to form
the DNA-binding intermediates.
PMID- 11006353
TI - Developmental and tissue-specific expression of AHR1, AHR2, and ARNT2 in dioxin
sensitive and -resistant populations of the marine fish Fundulus heteroclitus.
AB - Fundulus heteroclitus is a well-characterized marine fish model for studying aryl
hydrocarbon toxicity. The F. heteroclitus population in New Bedford Harbor (NBH),
a Superfund site in southeastern Massachusetts, exhibits heritable resistance to
the toxic effects of planar halogenated aromatic hydrocarbons (PHAHs), including
2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs).
To investigate the role of the aryl hydrocarbon receptor (AHR) signal
transduction pathway in PHAH resistance, we measured the relative levels of AHR1,
AHR2, and ARNT2 mRNA in whole embryos at different developmental stages and in
dissected tissues of adults, comparing expression of these genes in NBH fish with
fish from a reference site (Scorton Creek, MA [SC]). Expression of both AHR1 and
AHR2 mRNA increased during development, achieving maximum levels prior to
hatching. Maximal embryonic expression of AHR1 was delayed relative to AHR2.
Whole NBH and SC embryos exhibited no discernable differences in expression of
these genes. As we have previously observed, adult SC fish expressed AHR2 and
ARNT2 mRNA in all tissues examined, while AHR1 was expressed predominantly in
brain, heart, and gonads. In contrast, AHR1 mRNA was widely expressed in NBH
fish, appearing with unusual abundance in gill, gut, kidney, liver, and spleen.
This AHR1 expression pattern was not observed in the lab-reared progeny of NBH
fish, demonstrating that constitutive AHR1 expression in gill, gut, kidney,
liver, and spleen is not a heritable phenotype. Furthermore, widespread AHR1
expression was not induced in reference-site fish by TCDD or PCB mixtures,
suggesting that aberrant AHR1 expression is not simply a normal physiological
response of contaminant exposure. These results identify ubiquitous AHR1
expression as an attribute unique to feral NBH F. heteroclitus, and they
represent a first step in determining the regulatory mechanisms underlying this
expression pattern and its possible role in TCDD resistance.
PMID- 11006354
TI - Altered hepatic mRNA expression of apoptotic genes during dimethylnitrosamine
exposure.
AB - The role of TNFalpha in regulating apoptotic signaling was investigated during
subacute, low-dose (5.0 mg/kg) dimethylnitrosamine (DMN)-induced hepatotoxicity.
In TNFalpha receptor (TNFR) intact (wild-type, WT) mice following 4 and 7 DMN
exposures, hepatic transcripts for TNFalpha and TNFR-1 were elevated as compared
to vehicle controls. DMN hepatotoxicity in WT and TNFR-1/TNFR-2 double knockout
(DKO) mice were then compared over a 7-d exposure period. Liver RNA was isolated
to measure hepatic expression of TNFalpha/Fas-related genes and the Bcl-2 family
of genes that impact apoptosis. Hepatic mRNA levels for Fas, the apoptosis
promoting gene Bax, and the anti-apoptotic gene, Bcl-X(L), were up regulated
following 4 and 7 DMN exposures in both WT and TNFR DKO mice as compared to
vehicle controls. Notably, hepatic transcript levels for Bax were higher in TNFR
DKO mice treated with DMN compared to identically treated WT mice. However, we
detected approximately equal DMN-induced apoptotic degradation of liver DNA
following 1, 4, and 7 exposures in WT and TNFR DKO mice. Taken together, these
data show DMN-induced hepatic TNFalpha expression and suggest that TNFR-1
signaling may be up regulated following 4 and 7 daily DMN exposures. However,
TNFalpha is not required for apoptotic signaling at the mRNA transcript level
within the liver and instead may actually decrease Bax production.
PMID- 11006355
TI - Lack of selective developmental neurotoxicity in rat pups from dams treated by
gavage with chlorpyrifos.
AB - Pregnant Sprague-Dawley rats were given chlorpyrifos (O:, O-diethyl-O:-[3,5,6
trichloro-2-pyridinyl] phosphorothioate; CPF) in corn oil by gavage from
gestation day 6 (GD 6) through lactation day 10 (LD 10) at dosages of 0, 0.3, 1,
or 5 mg/kg/day in a developmental neurotoxicity study that conformed to U.S.
Environmental Protection Agency 1991 guidelines. GD 0 was the day when evidence
of mating was observed and postnatal day 0 (PND 0) was the day of birth. Toxicity
was limited to the highest dosage level (5 mg/kg/day) and, in the dams, consisted
of muscle fasciculation, hyperpnea, and hyperreactivity. A nonsignificant overall
trend toward weight gain and feed consumption was also observed in the high
dosage dams, with a statistically significant Group x Time interaction for
reduced weight gain in the 5-mg/kg/day group near the end of gestation. Although
many developmental indices were normal, pups from high-dosage dams had increased
mortality soon after birth, gained weight more slowly than controls, and had
several indications of slightly delayed maturation. The early deaths and delayed
maturation were attributed to maternal toxicity, though a possible contributing
role of direct pup toxicity in delayed development cannot be eliminated. In spite
of the apparent delay in physical development, high-dosage pups tested just after
weaning had normal learning and memory as tested on a T-maze spatial delayed
alternation task. Habituation, a primitive form of learning, was tested in 2
tasks (motor activity and auditory startle) and was not affected. No overt
effects were noted in either dams or pups at 1 or 0.3 mg/kg/day. Based on these
data, chlorpyrifos produced maternal and developmental toxicity in the 5
mg/kg/day-dosage group. There was no evidence of selective developmental
neurotoxicity following exposure to chlorpyrifos.
PMID- 11006356
TI - Stage- and species-specific developmental toxicity of all-trans retinoic acid in
four native North American ranids and Xenopus laevis.
AB - Within the last decade, there have been increasing reports of malformed
amphibians across North America. Recently, it has been suggested that hind-limb
malformations are a consequence of xenobiotic disruption of developmental
pathways regulated by retinoids. To assess the validity of this hypothesis, the
developmental toxicity of all-trans retinoic acid (RA) was examined in Xenopus
laevis and four North American anurans, at several life stages. To determine the
effects of RA on embryogenesis, mid-blastula stage embryos were exposed to 0,
6.25, 12.5, 25, or 50 ng RA/ml for 24 h. To evaluate the effects of RA on hind
limb development, early- and mid-limb bud stage tadpoles were exposed to RA
concentrations of 0, 250, 500, 750, 1000, or 1250 ng RA/ml for 24 h. Mid-blastula
RA exposure resulted in a concentration-dependent increase in dysmorphogenesis
and mortality in the three species examined (R. clamitans, R. septentrionalis and
X. laevis). RA exposure at stage 51 in X. laevis and stage 28 in R. sylvatica
resulted in concentration-dependent increases in reductions and deletions of the
hind limb. However, RA was ineffective at inducing hind-limb abnormalities in
stages 26 and 28 of R. pipiens, stage 28 in R. clamitans, or stage 48 in X.
laevis tadpoles. These results indicate that mid-blastula stage embryos are more
sensitive to RA-induced dysmorphogenesis and mortality than limb-bud stage
tadpoles. The significance of these findings is discussed in the context of the
possible occurrence of retinoid mimics in the environment.
PMID- 11006357
TI - Tissue disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in maternal and
developing long-evans rats following subchronic exposure.
AB - Prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces
alterations in the reproductive system of the developing pups. The objective of
this study was to determine the disposition of TCDD in maternal and fetal Long
Evans (LE) rats following subchronic exposure, since the adverse reproductive and
developmental effects have been extensively characterized in this strain of rat.
LE rats were dosed by gavage with 1, 10, or 30 ng [(3)H]TCDD/kg in corn oil, 5
days/week for 13 weeks. At the end of 13 weeks, females were mated and dosing
continued every day throughout gestation. Dams were sacrificed on gestation day
(GD) 9, GD16, GD21, and post-natal day 4 and analyzed for [(3)H]TCDD-derived
activity in maternal and fetal tissues. Maternal body burdens were equivalent at
different time points, indicating that the dams were at steady state. Maternal
body burdens were approximately 19, 120, and 300 ng TCDD/kg following doses of 1,
10, and 30 ng TCDD/kg, respectively. Individual embryo concentrations on GD9 were
1.6, 7, and 16 pg TCDD/g after maternal exposure of 1, 10, and 30 ng/kg/d,
respectively. On GD 16, fetal liver, urogenital tract, head, and body
concentrations were similar and averaged 1.4, 7.8, and 16.4 pg TCDD/g after
administration of 1, 10, or 30 ng TCDD/kg/d, respectively, indicating no
preferential sequestration within the different fetal tissues. These
concentrations of TCDD within fetal tissues after subchronic exposure are
comparable to those seen after a single dose of 50, 200, or 1000 ng TCDD/kg
administered on GD15, a critical period of gestation.
PMID- 11006358
TI - Evaluation of the developmental toxicity of formamide in Sprague-Dawley (CD)
rats.
AB - Timed-pregnant CD(R) outbred albino Sprague-Dawley rats received formamide (50,
100, or 200 mg/kg/day) or vehicle (5 ml/kg deionized/distilled water, po) on
gestational days (gd) 6 through 19. Maternal food and water consumption (absolute
and relative), body weight, and clinical signs were monitored at regular
intervals throughout gestation. At termination (gd 20), confirmed-pregnant
females (21-23 per group) were evaluated for clinical status and gestational
outcome; live fetuses were examined for external, visceral, and skeletal
malformations and variations. There were no maternal deaths and no dose-related
clinical signs. At 200 mg/kg/day, maternal body weight on gd 20, weight gain, and
gravid uterine weight were significantly decreased. Maternal weight gain,
corrected for gravid uterine weight, liver weight (absolute or relative), and
food and water consumption (absolute or relative), were not affected. Formamide
did not affect prenatal viability or incidences of fetal malformations or
variations. Average fetal body weight/litter was decreased at 100 and 200
mg/kg/day. Fetal body weight was affected at lower daily doses than in previously
published studies, possibly due to the longer total exposure period and/or lack
of a recovery period between cessation of exposure and termination. In summary,
the maternal toxicity no-observed-adverse-effect level (NOAEL) was 100 mg/kg/day
and the low observed adverse effect level (LOAEL) was 200 mg/kg/day under the
conditions of this study. Similarly, the developmental toxicity NOAEL was 50
mg/kg/day and the LOAEL was 100 mg/kg/day.
PMID- 11006359
TI - Reduced levels of 1,25-dihydroxyvitamin D(3) in rat dams and offspring after
exposure to a reconstituted PCB mixture.
AB - Previous studies revealed effects of polychlorinated biphenyls (PCBs) and other
polyhalogenated hydrocarbons on steroid hormone levels and hormone-dependent
functions including behavior. In the present study serum concentrations of the
vitamin D(3) metabolites 25-hydroxycholecalciferol (25-D) and 1,25
dihydroxycholecalciferol (1,25-D) were determined in rat dams and offspring after
exposure to a PCB mixture that was reconstituted according to the congener
pattern found in human breast milk. Unmated females were exposed to diets
adulterated with 0; 5; 20; or 40 mg PCBs/kg diet. Exposure started 50 days prior
to mating and was terminated at birth. Gestational exposure reduced serum
concentrations of 1,25-D in dams in a dose-dependent manner. Concentration of 25
D was also decreased at the time of delivery, but not at weaning. Determination
of 1,25-D in offspring at weaning revealed reductions in both high-exposure
groups. Levels of 25-D were diminished only at the highest exposure level.
Internal PCB concentrations in adipose tissue and brains exhibited a linear
relation to dosages in diet. Concentrations of PCBs in brains were similar in
dams and offspring at birth, but decreased at the end of lactation in dams. In
offspring, values increased during this period because of continued exposure via
the milk. In the adipose tissue, PCB levels were much lower in offspring than in
dams. To our knowledge, this is the first report of PCB-induced effects on
vitamin D(3) metabolites. In dams, reductions were seen even at the lowest
exposure level used. Further studies are needed to evaluate the biological
significance of these reductions in pregnant dams and possible consequences for
the developing offspring.
PMID- 11006360
TI - Antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse uterus:
critical role of the aryl hydrocarbon receptor in stromal tissue.
AB - The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the role of aryl
hydrocarbon receptor (AhR) in estradiol (E(2))-induced uterine epithelial
mitogenic activity and secretory protein mRNA expression were determined.
Ovariectomized wild-type (wt) and AhR-knockout (AhRKO) mice received oil, E(2),
or 5 microg/kg TCDD+E(2). E(2) stimulated similar large increases in the uterine
epithelial labeling index (LI) and mRNA abundance for the E(2)-dependent
epithelial secretory protein, lactoferrin (LF), in both wt and AhRKO mice.
However, uterine epithelial LI and LF mRNA were significantly reduced by
TCDD+E(2) in wt but not AhRKO mice. To determine the roles of stromal and
epithelial AhR in the TCDD effect, uterine stroma and epithelium from AhRKO and
wt mice were enzymatically separated and recombined into four types of tissue
recombinants that either contained or lacked AhR in one or more tissue
compartments. Tissue recombinants were grafted into nude mice, which were later
ovariectomized and given oil, E(2), or TCDD+E(2). Epithelial LI was significantly
reduced by TCDD in grafts containing stromal AhR, regardless of epithelial AhR
status. However, LI was unaffected by TCDD in grafts lacking stromal AhR, even
when epithelial AhR was present. Thus, TCDD inhibits E(2)-induced uterine
epithelial mitogenic and secretory activity, and this requires AhR. Anti
proliferative effects of TCDD on uterine epithelia appear to be mediated
indirectly through stromal AhR, suggesting that liganded AhR alters epithelial
function by disrupting normal E(2)-induced stromal activity. This is the first
demonstration that TCDD impairs uterine epithelial function by altering normal
stromal-epithelial interactions in vivo.
PMID- 11006361
TI - Application of a hybrid CFD-PBPK nasal dosimetry model in an inhalation risk
assessment: an example with acrylic acid.
AB - The available inhalation toxicity information for acrylic acid (AA) suggests that
lesions to the nasal cavity, specifically olfactory degeneration, are the most
sensitive end point for developing a reference concentration (RfC). Advances in
physiologically based pharmacokinetic (PBPK) modeling, specifically the
incorporation of computational fluid dynamic (CFD) models, now make it possible
to estimate the flux of inhaled chemicals within the nasal cavity of experimental
species, specifically rats. The focus of this investigation was to apply an
existing CFD-PBPK hybrid model in the estimation of an RfC to determine the
impact of incorporation of this new modeling technique into the risk assessment
process. Information provided in the literature on the toxicity and mode of
action for AA was used to determine the risk assessment approach. A comparison of
the approach used for the current U.S. Environmental Protection Agency (U.S. EPA)
RfC with the approach using the CFD-PBPK hybrid model was also conducted. The
application of the CFD-PBPK hybrid model in a risk assessment for AA resulted in
an RfC of 79 ppb, assuming a minute ventilation of 13.8 l/min (20 m(3)/day) in
humans. This value differs substantially from the RfC of 0.37 ppb estimated for
AA by the U.S. EPA before the PBPK modeling advances became available. The
difference in these two RfCs arises from many factors, with the main difference
being the species selected (mouse vs. rat). The choice to conduct the evaluation
using the rat was based on the availability of dosimetry data in this species.
Once these data are available in the mouse, an assessment should be conducted
using this information. Additional differences included the methods used for
estimating the target tissue concentration, the uncertainty factors (UFs)
applied, and the application of duration and uncertainty adjustments to the
internal target tissue dose rather than the external exposure concentration.
PMID- 11006362
TI - Metabonomics: evaluation of nuclear magnetic resonance (NMR) and pattern
recognition technology for rapid in vivo screening of liver and kidney toxicants.
AB - The purpose of this study was to evaluate the feasibility of metabonomics
technology for developing a rapid-throughput toxicity screen using 2 known
hepatotoxicants: carbon tetrachloride (CCl(4)) and alpha-naphthylisothiocyanate
(ANIT) and 2 known nephrotoxicants: 2-bromoethylamine (BEA) and 4-aminophenol
(PAP). In addition, the diuretic furosemide (FURO) was also studied. Single doses
of CCl(4) (0.1 and 0.5 ml/kg), ANIT (10 and 100 mg/kg), BEA (15 and 150 mg/kg),
PAP (15 and 150 mg/kg) and FURO (1 and 5 mg) were administered as single IP or
oral doses to groups of 4 male Wistar rats/dose. Twenty-four-h urine samples were
collected pretest, daily through Day 4, and on Day 10 (high dose CCl(4) and BEA
only). Blood samples were taken on Days 1, 2, and 4 or 1, 4, and 10 for clinical
chemistry assessment, and the appropriate target organ was examined
microscopically. NMR spectra of urine were acquired and the data processed and
subjected to principal component analyses (PCA). The results demonstrated that
the metabonomic approach could readily distinguish the onset and reversal of
toxicity with good agreement between clinical chemistry and PCA data. In at least
2 instances (ANIT and BEA), PCA analysis suggested effects at low doses, which
were not as evident by clinical chemistry or microscopic analysis. Furosemide,
which had no effect at the doses employed, did not produce any changes in PCA
patterns. These data support the contention that the metabonomic approach
represents a promising new technology for the development of a rapid throughput
in vivo toxicity screen.
PMID- 11006363
TI - Peroxisome proliferator-activated receptor alpha-null mice lack resistance to
acetaminophen hepatotoxicity following clofibrate exposure.
AB - The purpose of this study was to investigate whether activation of the nuclear
receptor PPARalpha is needed for protection from acetaminophen (APAP)
hepatotoxicity produced by repeated administration of the peroxisome proliferator
clofibrate (CFB). Female wild-type and PPARalpha-null mice received corn oil
vehicle or 500 mg CFB/kg, ip, daily for 10 days. They were then fasted overnight
(18 h) and either killed at 4 or 24 h after challenge with 400 mg APAP/kg.
Controls received 50% propylene glycol vehicle only. In this model of CFB
hepatoprotection, liver injury was assessed by measuring plasma sorbitol
dehydrogenase activity and by histopathology at 24 h after APAP challenge.
Significant hepatocellular necrosis was evident in both corn oil-pretreated
PPARalpha-null and wild-type mice at 24 h after APAP challenge. In agreement with
previous studies, CFB-pretreated wild-type mice showed marked protection against
APAP toxicity. In contrast, CFB did not provide protection against APAP
hepatotoxicity in the PPARalpha-null mice. Similarly, at 4 h after APAP
challenge, hepatic glutathione depletion and selective arylation of cytosolic
proteins were reduced significantly in CFB-pretreated wild-type mice, but not in
PPARalpha-null mice. The lack of changes in APAP binding and NPSH depletion in
CFB-pretreated, PPARalpha-null mice is consistent with the presence of
significant liver injury at 24 h in this treatment group. These findings
demonstrate that the protection against APAP hepatotoxicity by peroxisome
proliferator treatment is mediated by the activation of PPARalpha.
PMID- 11006364
TI - CD4(+) T-cell activation and induction of autoimmune hepatitis following
trichloroethylene treatment in MRL+/+ mice.
AB - Exposure to relatively high levels of trichloroethylene has recently been shown
to accelerate the development of an autoimmune response in the autoimmune prone
MRL+/+ mice. The trichloroethylene-induced autoimmune response was associated
with an increase in activated CD4(+) T cells, producing Th(1)-like cytokines. The
present study was conducted to determine whether lower, more occupationally
relevant doses of trichloroethylene could also promote autoimmunity, in MRL+/+
mice, and if so, to investigate the mechanism of this accelerated autoimmune
response. In addition, histological studies were performed to determine if
trichloroethylene was capable of producing pathological markers consistent with
an autoimmune disease. Trichloroethylene was administered to mice in the drinking
water at 0, 0.1, 0.5, and 2.5 mg/ml for 4 and 32 weeks. There was a significant
increase above controls in serum antinuclear antibody (ANA) levels following 4
weeks of both 0.1 and 0.5 mg/kg/day of trichloroethylene. After 32 weeks of
treatment, ANA levels were elevated and equal in all groups. The kinetics of the
ANA response indicated that trichloroethylene accelerated the innate autoimmune
response in the MRL+/+ mice. There was a dose-related increase in the percentage
of activated CD4(+) T cells in both the spleens and lymph nodes of mice treated
for 32 weeks with trichloroethylene when compared to controls. CD4(+) T cells
isolated from MRL+/+ mice after either 4 or 32 weeks of treatment with
trichloroethylene secreted inflammatory or Th(1)-like cytokines. Following 32
weeks of trichloroethylene treatment, there was a significant increase in hepatic
mononuclear infiltration localized to the portal region, a type of hepatic
infiltration consistent with autoimmune hepatitis. Taken collectively, these data
suggest that exposure to occupationally relevant concentrations of
trichloroethylene can accelerate an autoimmune response and can lead to
autoimmune disease. The mechanism of this autoimmunity appears to involve, at
least in part, activated CD4(+) T cells that then produced inflammatory
cytokines.
PMID- 11006365
TI - Intramuscular interferon beta-1a therapy initiated during a first demyelinating
event in multiple sclerosis. CHAMPS Study Group.
AB - BACKGROUND: Treatment with interferon beta has been shown to help patients with
established multiple sclerosis, but it is not known whether initiating treatment
at the time of a first clinical demyelinating event is of value. METHODS: We
conducted a randomized, double-blind trial of 383 patients who had a first acute
clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or
brain-stem or cerebellar syndrome) and evidence of prior subclinical
demyelination on magnetic resonance imaging (MRI) of the brain. After initial
treatment with corticosteroids, 193 patients were randomly assigned to receive
weekly intramuscular injections of 30 microg of interferon beta-1a and 190 were
assigned to receive weekly injections of placebo. The study end points were the
development of clinically definite multiple sclerosis and changes in findings on
MRI of the brain. The trial was stopped after a preplanned interim efficacy
analysis. RESULTS: During three years of follow-up, the cumulative probability of
the development of clinically definite multiple sclerosis was significantly lower
in the interferon beta-1a group than in the placebo group (rate ratio, 0.56; 95
percent confidence interval, 0.38 to 0.81; P=0.002). As compared with the
patients in the placebo group, patients in the interferon beta-1a group had a
relative reduction in the volume of brain lesions (P<0.001), fewer new or
enlarging lesions (P<0.001), and fewer gadolinium-enhancing lesions (P<0.001) at
18 months. CONCLUSIONS: Initiating treatment with interferon beta-1a at the time
of a first demyelinating event is beneficial for patients with brain lesions on
MRI that indicate a high risk of clinically definite multiple sclerosis.
PMID- 11006366
TI - Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer.
Irinotecan Study Group.
AB - BACKGROUND: The combination of fluorouracil and leucovorin has until recently
been standard therapy for metastatic colorectal cancer. Irinotecan prolongs
survival in patients with colorectal cancer that is refractory to treatment with
fluorouracil and leucovorin. In a multicenter trial, we compared a combination of
irinotecan, fluorouracil and leucovorin with bolus doses of fluorouracil and
leucovorin as first-line therapy for metastatic colorectal cancer. A third group
of patients received irinotecan alone. METHODS: Patients were randomly assigned
to receive irinotecan (125 mg per square meter of body-surface area
intravenously), fluorouracil (500 mg per square meter as an intravenous bolus),
and leucovorin (20 mg per square meter as an intravenous bolus) weekly for four
weeks every six weeks; fluorouracil (425 mg per square meter as an intravenous
bolus) and leucovorin (20 mg per square meter as an intravenous bolus) daily for
five consecutive days every four weeks; or irinotecan alone (125 mg per square
meter intravenously) weekly for four weeks every six weeks. End points included
progression-free survival and overall survival. RESULTS: Of 683 patients, 231
were assigned to receive irinotecan, fluorouracil, and leucovorin; 226 to receive
fluorouracil and leucovorin; and 226 to receive irinotecan alone. In an intention
to-treat analysis, as compared with treatment with fluorouracil and leucovorin,
treatment with irinotecan, fluorouracil, and leucovorin resulted in significantly
longer progression-free survival (median, 7.0 vs. 4.3 months; P=0.004), a higher
rate of confirmed response (39 percent vs. 21 percent, P<0.001), and longer
overall survival (median, 14.8 vs. 12.6 months; P=0.04). Results for irinotecan
alone were similar to those for fluorouracil and leucovorin. Grade 3 (severe)
diarrhea was more common during treatment with irinotecan, fluorouracil, and
leucovorin than during treatment with fluorouracil and leucovorin, but the
incidence of grade 4 (life-threatening) diarrhea was similar in the two groups
(<8 percent). Grade 3 or 4 mucositis, grade 4 neutropenia, and neutropenic fever
were less frequent during treatment with irinotecan, fluorouracil, and
leucovorin. Adding irinotecan to the regimen of fluorouracil and leucovorin did
not compromise the quality of life. CONCLUSIONS: Weekly treatment with irinotecan
plus fluorouracil and leucovorin is superior to a widely used regimen of
fluorouracil and leucovorin for metastatic colorectal cancer in terms of
progression-free survival and overall survival.
PMID- 11006367
TI - Multiple complex coronary plaques in patients with acute myocardial infarction.
AB - BACKGROUND: Acute myocardial infarction is believed to be caused by rupture of an
unstable coronary-artery plaque that appears as a single lesion on angiography.
However, plaque instability might be caused by pathophysiologic processes, such
as inflammation, that exert adverse effects throughout the coronary vasculature
and that therefore result in multiple unstable lesions. METHODS: To document the
presence of multiple unstable plaques in patients with acute myocardial
infarction and determine their influence on outcome, we analyzed angiograms from
253 patients for complex coronary plaques characterized by thrombus, ulceration,
plaque irregularity, and impaired flow. RESULTS: Single complex coronary plaques
were identified in 153 patients (60.5 percent) and multiple complex plaques in
the other 100 patients (39.5 percent). As compared with patients with single
complex plaques, those with multiple complex plaques were less likely to undergo
primary angioplasty (86.0 percent vs. 94.8 percent, P = 0.03) and more commonly
required urgent bypass surgery (27.0 percent vs. 5.2 percent, P < or = 0.001).
During the year after myocardial infarction, the presence of multiple complex
plaques was associated with an increased incidence of recurrent acute coronary
syndromes (19.0 percent vs. 2.6 percent, P < or = 0.001); repeated angioplasty
(32.0 percent vs. 12.4 percent, P < or = 0.001), particularly of non-infarct
related lesions (17.0 percent vs. 4.6 percent, P < or = 0.001); and coronary
artery bypass graft surgery (35.0 percent vs. 11.1 percent, P < or = 0.001).
CONCLUSIONS: Patients with acute myocardial infarction may harbor multiple
complex coronary plaques that are associated with adverse clinical outcomes.
Plaque instability may be due to a widespread process throughout the coronary
vessels, which may have implications for the management of acute ischemic heart
disease.
PMID- 11006368
TI - Effect of growth hormone treatment on the adult height of children with chronic
renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal
Failure.
AB - BACKGROUND: Growth hormone treatment stimulates growth in short children with
chronic renal failure. However, the extent to which this therapy increases final
adult height is not known. METHODS: We followed 38 initially prepubertal children
with chronic renal failure treated with growth hormone for a mean of 5.3 years
until they reached their final adult height. The mean (+/-SD) age at the start of
treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the
mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic
renal failure who were not treated with growth hormone served as controls.
RESULTS: The children treated with growth hormone had sustained catch-up growth,
whereas the control children had progressive growth failure. The mean final
height of the growth hormone-treated children was 165 cm for boys and 156 cm for
girls. The mean final adult height of the growth hormone-treated children was
1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at
base line (P< 0.001). In contrast, the final height of the untreated children
(2.1+/-1.2 SD below normal) was 0.6 SD below their standardized height at base
line (P<0.001). Although prepubertal bone maturation was accelerated in growth
hormone-treated children, treatment was not associated with a shortening of the
pubertal growth spurt. The total height gain was positively associated with the
initial target-height deficit and the duration of growth hormone therapy and was
negatively associated with the percentage of the observation period spent
receiving dialysis treatment. CONCLUSIONS: Long-term growth hormone treatment of
children with chronic renal failure induces persistent catch-up growth, and the
majority of patients achieve normal adult height.
PMID- 11006369
TI - Liver disease in patients with hereditary hemorrhagic telangiectasia.
AB - BACKGROUND: Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease,
is an autosomal dominant disorder characterized by angiodysplastic lesions
(telangiectases and arteriovenous malformations) that affect many organs. Liver
involvement in patients with this disease has not been fully characterized.
METHODS: We studied the clinical findings and results of hemodynamic,
angiographic, and imaging studies in 19 patients with hereditary hemorrhagic
telangiectasia and symptomatic liver involvement. RESULTS: We evaluated 14 women
and 5 men who ranged in age from 34 to 74 years. All but one of the patients had
a hyperdynamic circulation (cardiac index, 4.2 to 7.3 liters per minute per
square meter of body-surface area). In eight patients, the clinical findings were
consistent with the presence of high-output heart failure. The cardiac index and
pulmonary-capillary wedge pressure were elevated in the six patients in whom
these measurements were performed. After a median period of 24 months, the
condition of three of the eight patients had improved, four were in stable
condition with medical therapy, and one had died. Six patients had manifestations
of portal hypertension such as ascites or variceal bleeding. The hepatic
sinusoidal pressure was elevated in the four patients in whom it was measured.
After a median period of 19 months, the condition of two of the six patients had
improved, and the other four had died. Five patients had manifestations of
biliary disease, such as an elevated alkaline phosphatase level and abnormalities
on bile duct imaging. After a median period of 30 months, the condition of two of
the five had improved, the condition of one was unchanged, heart failure had
developed in one, and one had died after an unsuccessful attempt at liver
transplantation. CONCLUSIONS: In patients with hereditary hemorrhagic
telangiectasia and symptomatic liver-involvement, the typical clinical
presentations include high-output heart failure, portal hypertension, and biliary
disease.
PMID- 11006370
TI - Images in clinical medicine. Mesenteric ischemia.
PMID- 11006371
TI - Multiple sclerosis.
PMID- 11006372
TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological
exercises. Case 30-2000. A 25-year-old man with asthma, cardiac failure,
diarrhea, and weakness of the right hand.
PMID- 11006373
TI - Moving beyond fluorouracil for colorectal cancer.
PMID- 11006374
TI - Correction: The Effect of Previous Coronary-Artery Bypass Surgery on the
Prognosis of Patients with Diabetes Who Have Acute Myocardial Infarction.
PMID- 11006375
TI - Correction: Lack of Effect of a High-Fiber Cereal Supplement on the Recurrence of
Colorectal Adenomas.
PMID- 11006376
TI - A fibril reinforced nonhomogeneous poroelastic model for articular cartilage:
inhomogeneous response in unconfined compression.
AB - The depth dependence of material properties of articular cartilage, known as the
zonal differences, is incorporated into a nonlinear fibril-reinforced poroelastic
model developed previously in order to explore the significance of material
heterogeneity in the mechanical behavior of cartilage. The material variations
proposed are based on extensive observations. The collagen fibrils are modeled as
a distinct constituent which reinforces the other two constituents representing
proteoglycans and water. The Young's modulus and Poisson's ratio of the drained
nonfibrillar matrix are so determined that the aggregate compressive modulus for
confined geometry fits the experimental data. Three nonlinear factors are
considered, i.e. the effect of finite deformation, the dependence of permeability
on dilatation and the fibril stiffening with its tensile strain. Solutions are
extracted using a finite element procedure to simulate unconfined compression
tests. The features of the model are then demonstrated with an emphasis on the
results obtainable only with a nonhomogeneous model, showing reasonable agreement
with experiments. The model suggests mechanical behaviors significantly different
from those revealed by homogeneous models: not only the depth variations of the
strains which are expected by qualitative analyses, but also, for instance, the
relaxation-time dependence of the axial strain which is normally not expected in
a relaxation test. Therefore, such a nonhomogeneous model is necessary for better
understanding of the mechanical behavior of cartilage.
PMID- 11006377
TI - Tensegrity architecture explains linear stiffening and predicts softening of
living cells.
AB - The problem of theoretical explanation of the experimentally observed linear
stiffening of living cells is addressed. This explanation is based on Ingber's
assumption that the cell cytoskeleton, which enjoys tensegrity architecture with
compressed microtubules that provide tension to the microfilaments, affects the
mechanical behavior of the living cell. Moreover, it is shown that the
consideration of the extreme flexibility of microtubules and the unilateral
response of microfilaments is crucial for the understanding of the living cell
overall behavior. Formal nonlinear structural analysis of the cell cytoskeleton
under external mechanical loads is performed. For this purpose, a general
computer model for tensegrity assemblies with unilateral microfilaments and
buckled microtubules is developed and applied to the theoretical analysis of the
mechanical response of 2D and 3D examples of tensegrity cells mimicking the
behavior of real living cells. Results of the computer simulations explain the
experimentally observed cell stiffening. Moreover, the theoretical results
predict the possible existence of a transient softening behavior of cells, a
phenomenon, which has not been observed in experiments yet.
PMID- 11006378
TI - Knoop microhardness anisotropy of the ovine radius.
AB - The Knoop indenter has been used to characterise fully the Knoop microhardness
(H(K)) anisotropy of compact bone. 2120 indentations were performed on mature
ovine radii and a linear relationship was found between H(K) and the angle
between the major diagonal of the indenter and the lamella boundaries (p<<0.001).
H(K) increased significantly with ash fraction (p<0.001), but decreased with
atmospheric vapour pressure (p<0.05). A significant interaction was found between
ash fraction and atmospheric vapour pressure (p<0.01). H(K) significantly varied
with indentation position along the diaphysis and around the cortex (both
p<<0.001), however radial variation in H(K) was not statistically significant.
The variation of ash fraction showed similar trends. These data show that H(K)
varies similarly to Vickers microhardness, but in addition, can provide clear
information on the anisotropy of Haversian bone without the need for excising
many different indentation planes. A large number of indentations are required to
obtain low type I and type II errors in the statistical analysis.
PMID- 11006379
TI - In vitro axial preload application during spine flexibility testing: towards
reduced apparatus-related artefacts.
AB - Presently, there is little consensus about how, or even if, axial preload should
be incorporated in spine flexibility tests in order to simulate the compressive
loads naturally present in vivo. Some preload application methods are suspected
of producing unwanted "artefact" forces as the specimen rotates and, in doing so,
influencing the resulting kinematics. The objective of this study was to
quantitatively compare four distinct types of preload which have roots in
contemporary experimental practice. The specific quantities compared were the
reaction moments and forces resulting at the intervertebral disc and specimen
kinematics. The preload types incorporated increasing amounts of caudal
constraint on the preload application vector ranging from an unconstrained dead
load arrangement to an apparatus that allowed the vector to follow rotations of
the specimen. Six human cadaveric spine segments were tested (1-L1/L2, 3-L2/L3, 1
L3/L4 and 1-L4/L5). Pure moments were applied to the specimens with each of the
four different types of compressive preload. Kinematic response was measured
using an opto-electronic motion analysis system. A six-axis load cell was used to
measure reaction forces and moments. Artefact reaction moments and shear forces
were significantly affected by preload application method and magnitude.
Unconstrained preload methods produced high artefact moments and low artefact
shear forces while more constrained methods did the opposite. A mechanical trade
off is suggested by our results, whereby unwanted moment can only be prevented at
the cost of shear force production. When comparing spine flexibility studies,
caution should be exercised to ensure preload was applied in a similar manner for
all studies. Unwanted moments or forces induced as a result of preload
application method may render the comparison of two seemingly similar studies
inappropriate.
PMID- 11006380
TI - Collagen fibril D-period may change as a function of strain and location in
ligament.
AB - The purpose of this study was to determine if the characteristic banding pattern
(D-period) of collagen fibrils from rabbit medial collateral ligaments changes as
a function of gross ligament strain and, if so, whether the changes are location
dependent (insertion versus midsubstance). Femur-medial collateral ligament-tibia
complexes were strained to 0, 8, or 12% and immediately chemically fixed in situ.
Samples were taken from the medial collateral ligament midsubstance and bony
insertions, and prepared for and observed under a transmission electron
microscope. D-period length was measured and found to increase (albeit not
significantly so, p=0. 1) as a function of gross strain for samples obtained from
the insertion sites but not for samples obtained from the ligament midsubstance.
Results suggested that ligament strains are inhomogeneous at the ultrastructural
level.
PMID- 11006381
TI - High-resolution finite element models with tissue strength asymmetry accurately
predict failure of trabecular bone.
AB - The ability to predict trabecular failure using microstructure-based
computational models would greatly facilitate study of trabecular structure
function relations, multiaxial strength, and tissue remodeling. We hypothesized
that high-resolution finite element models of trabecular bone that include
cortical-like strength asymmetry at the tissue level, could predict apparent
level failure of trabecular bone for multiple loading modes. A bilinear
constitutive model with asymmetric tissue yield strains in tension and
compression was applied to simulate failure in high-resolution finite element
models of seven bovine tibial specimens. Tissue modulus was reduced by 95% when
tissue principal strains exceeded the tissue yield strains. Linear models were
first calibrated for effective tissue modulus against specimen-specific
experimental measures of apparent modulus, producing effective tissue moduli of
(mean+/-S.D.) 18.7+/-3.4GPa. Next, a parameter study was performed on a single
specimen to estimate the tissue level tensile and compressive yield strains.
These values, 0.60% strain in tension and 1.01% strain in compression, were then
used in non-linear analyses of all seven specimens to predict failure for
apparent tensile, compressive, and shear loading. When compared to apparent yield
properties previously measured for the same type of bone, the model predictions
of both the stresses and strains at failure were not statistically different for
any loading case (p>0.15). Use of symmetric tissue strengths could not match the
experimental data. These findings establish that, once effective tissue modulus
is calibrated and uniform but asymmetric tissue failure strains are used, the
resulting models can capture the apparent strength behavior to an outstanding
level of accuracy. As such, these computational models have reached a level of
fidelity that qualifies them as surrogates for destructive mechanical testing of
real specimens.
PMID- 11006382
TI - Serum modulates the intracellular calcium response of primary cultured bone cells
to shear flow.
AB - We investigated the effect of newborn bovine serum on the intracellular calcium
[Ca(2+)](i) response of primary cultured bone cells stimulated by fluid flow. As
it has been previously established that these cells exhibit [Ca(2+)](i) responses
to fluid flow shear stress in saline media without growth factors or other
chemically stimulatory factors, we hypothesized that the addition of serum to the
flow medium would enhance the mechanosensitivity of the cells. We examined the
effect of a short-term (10-15min) exposure of the cells to 2 and 10% serum prior
to flow stimulation (pretreated) compared to not exposing the cells prior to flow
stimulation (unpretreated). The cells were subjected to a well-defined, 90-s flow
stimulus with shear stress levels ranging from 0.02 to 3.5Pa in a laminar flow
chamber using a saline medium supplemented with 2 or 10% serum. For pretreatment,
the serum concentration was the same from pre-flow to flow exposure. We observed
a differential effect in the magnitude of the peak [Ca(2+)](i) response modulated
by the concentration of serum in the pre-flow medium. Additionally, ATP
supplemented flow was examined as a comparison to the serum-supplemented flow and
exhibited a similar trend in the peak [Ca(2+)](i) flow response that was
dependent on ATP concentration and pre-flow exposure conditions. These findings
demonstrate that under the conditions of this study, chemical agonist exposure
can modulate the [Ca(2+)](i) response in bone cells subjected to fluid flow
induced shear stress.
PMID- 11006383
TI - Digital automated RSA compared to manually operated RSA.
AB - The accuracy of digital Roentgen stereophotogrammetric analysis (RSA) was
compared to the accuracy of a manually operated RSA system. For this purpose, we
used radiographs of a phantom and radiographs of patients. The radiographs of the
patients consisted of double examinations of 12 patients that had a tibial
osteotomy and of double examinations of 12 patients that received a total hip
prosthesis. First, the radiographs were measured manually with an accurate
measurement table. Subsequently, the images were digitized by a film scanner at
150 DPI and 300 DPI resolutions and analyzed with the RSA-CMS software. In the
phantom experiment, the manually operated system produced significantly better
results than the digital system, although the maximum difference between the
median values of the manually operated system and the digital system was as low
as 0.013mm for translations and 0.033 degrees for rotations. In the radiographs
of the patients, the manually operated system and the digital system produced
equally accurate results: no significant differences in translations and
rotations were found. We conclude that digital RSA is an accurate, fast, and user
friendly alternative for manually operated RSA. Currently, digital RSA systems
are being used in a growing number of clinical RSA-studies.
PMID- 11006384
TI - Quantification of fingertip force reduction in the forefinger following simulated
paralysis of extensor and intrinsic muscles.
AB - Objective estimates of fingertip force reduction following peripheral nerve
injuries would assist clinicians in setting realistic expectations for
rehabilitating strength of grasp. We quantified the reduction in fingertip force
that can be biomechanically attributed to paralysis of the groups of muscles
associated with low radial and ulnar palsies. We mounted 11 fresh cadaveric hands
(5 right, 6 left) on a frame, placed their forefingers in a functional posture
(neutral abduction, 45 degrees of flexion at the metacarpophalangeal and proximal
interphalangeal joints, and 10 degrees at the distal interphalangeal joint) and
pinned the distal phalanx to a six-axis dynamometer. We pulled on individual
tendons with tensions up to 25% of maximal isometric force of their associated
muscle and measured fingertip force and torque output. Based on these
measurements, we predicted the optimal combination of tendon tensions that
maximized palmar force (analogous to tip pinch force, directed perpendicularly
from the midpoint of the distal phalanx, in the plane of finger flexion
extension) for three cases: non-paretic (all muscles of forefinger available),
low radial palsy (extrinsic extensor muscles unavailable) and low ulnar palsy
(intrinsic muscles unavailable). We then applied these combinations of tension to
the cadaveric tendons and measured fingertip output. Measured palmar forces were
within 2% and 5 degrees of the predicted magnitude and direction, respectively,
suggesting tendon tensions superimpose linearly in spite of the complexity of the
extensor mechanism. Maximal palmar forces for ulnar and radial palsies were 43
and 85% of non-paretic magnitude, respectively (p<0.05). Thus, the reduction in
tip pinch strength seen clinically in low radial palsy may be partly due to loss
of the biomechanical contribution of forefinger extrinsic extensor muscles to
palmar force. Fingertip forces in low ulnar palsy were 9 degrees further from the
desired palmar direction than the non-paretic or low radial palsy cases (p<0.05).
PMID- 11006385
TI - Large-sliding contact elements accurately predict levels of bone-implant
micromotion relevant to osseointegration.
AB - Primary stability is recognised as an important determinant in the aseptic
loosening failure process of cementless implants. An accurate evaluation of the
bone-implant relative micromotion is becoming important both in pre-clinical and
clinical studies. If the biological threshold for micro-movements is in the range
100-200 micrometer then, in order to be discriminative, any method used to
evaluate the primary stability should have an accuracy of 10-20 micrometer or
better. Additionally, such method should also be able to report the relative
micromotion at each point of the interface. None of the available experimental
methods satisfies both requirements. Aim of the present study is to verify if any
of the current finite element modelling techniques is sufficiently accurate in
predicting the primary stability of a cementless prosthesis to be used to decide
whether the micromotion may or may not jeopardise the implant osseointegration.
The primary stability of an anatomic cementless stem, as measured in vitro, was
used as a benchmark problem to comparatively evaluate different contact modelling
techniques. Frictionless contact, frictional contact and press-fitted frictional
contact conditions were modelled using alternatively node-to-node, node-to-face
and face-to-face contact elements. The model based on face-to-face contact
elements accounting for frictional contact and initial press-fit was able to
predict the micromotion measured experimentally with an average (RMS) error of 10
micrometer and a peak error of 14 micrometer. All the other models presented
errors higher than 20 micrometer assumed in the present study as an accuracy
threshold.
PMID- 11006386
TI - Predicted region of stability for balance recovery: motion at the knee joint can
improve termination of forward movement.
AB - Earlier experimental studies on balance recovery following perturbation have
identified two discrete strategies commonly employed by humans, i.e. hip and
ankle strategies. It has hence been implied that the knee joint plays a
relatively minor role in balance recovery. The purpose of this study was to
determine whether the size of the feasible stability region (FSR) would be
affected by allowing knee motion in sagittal plane movement termination. The FSR
was defined as the feasible range of anterior velocities of the center of mass
(COM) of a human subject that could be reduced to zero with the final COM
position within the base of support (BOS) limits. The FSR was computed using a
four-segment biomechanical model and optimization routine based on Simulated
Annealing algorithm for three scenarios: unrestricted knee motion (UK),
restricted knee motion (RK), and unrestricted knee motion with an initial posture
that matches RK (UKM). We found that movement termination could benefit little
from UK condition when the COM (x(COM)) was initially located in the forefoot
region [0.00 (toe) >x(COM)>/=-0.50 (mid-foot)] with no more than a 17% increase
in FSR compared to RK. The effect of knee motion increased in the rear foot
region with a 25% increase in FSR at x(COM)=-1 (heel). Close to half of this
difference (12%) was attributable to the knee-related restriction on initial
posture and the rest to movement termination per se. These findings illustrated a
theoretical role of knee motion in standing humans' repertoire of effective
posture responses, which include hip and ankle strategies and their variants for
balance recovery with stationary BOS.
PMID- 11006387
TI - The glenohumeral joint rotation centre in vivo.
AB - Within the framework of the current call for standardization in upper extremity
research, three methods to determine the glenohumeral joint rotation centre in
vivo were tested. Therefore, subjects performed humeral movements, while a 3D
electromagnetic tracking device registered the motion of the humerus with respect
to the scapula. For the first method to estimate the glenohumeral joint rotation
centre five scapular bony landmarks served as input to regression equations. The
second method fitted a sphere through the humeral position data and the third
method calculated the rotation centre determining an optimal helical axis. The
experiment consisted of two parts, at first one subject was measured 10 times,
subsequently one observer measured 10 subjects twice and another observer
measured these subjects once. The first part of the experiment demonstrated that
all methods are capable to reproduce the rotation centre within 4mm, but the
location of the centre differed significantly between methods (p<0.001). The
second part, showed that inter- and intra-observer reliability was sufficiently
for the sphere-fitting method and for the helical-axes method. The two
observations of one observer differed significantly (p<0.008) using the
regression method. The authors prefer the helical-axes method, it is a reliable
and valid method which can be applied in movement registration of healthy
subjects and patients with a shoulder endoprosthesis, it can be applied in hinge
joints to determine a rotation axis instead of a rotation centre which is
desirable in standardized upper extremity research, and calculation time is
short.
PMID- 11006388
TI - Numerical 3D analysis of oscillatory flow in the time-varying laryngeal channel.
AB - Three-dimensional flow through an anatomically representative model of the human
larynx has been numerically simulated. This model includes the vestibular folds,
the vocal cords and the glottic and subglottic areas. Pseudo-time-varying glottic
aperture and flow conditions have been considered during quiet breathing, with a
peak volume flow rate of 0.75l/s and a frequency of 0.25Hz. Because of the severe
constriction, jet-like configurations have been observed. Minor differences have
been outlined between the inspiration and expiration profiles. Simulations
demonstrated the presence of a backflow region which may extend to 60mm from the
glottis at peak inspiration and occupy 20% of the tracheal cross section. Because
of its rolling, this backflow region appears in the sagittal plane close to the
anterior wall, only one diameter from the laryngeal constriction and extends over
about 40mm. The evolution of the streamwise velocity contours and of the
corresponding secondary vector plots at six critical stations, including the
glottic section, has also been described. A double pair of counter-rotating
vortices develops shortly downstream/upstream from the orifice respectively at
inspiration/expiration and merges near the frontal plane about 25mm from the
glottis. The effect of the incoming flow has been evaluated by including the
pharyngeal channel; no major difference has been observed in the computed flow
patterns.
PMID- 11006389
TI - Acetabular morphology and resurfacing design.
AB - The bony surfaces of 18 archaeological hemipelves were scanned using a 3D laser
surface scanner and CyDir software on a Silicon Graphics workstation. The
acetabular area was selected and point data from the approximately spherical bone
surface saved. These data were input to a MATLAB routine that calculated the
radius and centre of the best-fit sphere. The goodness of fit was estimated using
the mean and standard deviation of the distance of the bone surface points from
the sphere surface. Eight points, at approximately equal distances around the
acetabular rim, were selected with reference to bony landmarks. A plane
containing three of these points served as an orientation reference plane. The
vectors joining the eight rim points to the centre of the best-fit sphere were
found. The angles between these vectors and the normal to the reference plane
were calculated. Paired angles were summed to give the angle subtended by the
acetabular rim in four directions. The overall mean angle was 158 degrees (range
of mean angles 145 degrees -173 degrees ). The largest individual angles, some
exceeding 180 degrees, were in the superior-inferior direction, while the mean
angle in the anterior-posterior direction, i.e. that controlling flexion
extension, was 152 degrees. Males had larger subtended angles than females,
although the difference was not statistically significant. Simulated reaming
increased all angles by approximately 10 degrees. The subtended angles are
important parameters in the design of the acetabular component of a hip
replacement and particularly important in resurfacing hip replacement when the
volume available is tightly constrained.
PMID- 11006390
TI - Analysis of a femoral hip prosthesis designed to reduce stress shielding.
AB - The natural stress distribution in the femur is significantly altered after total
hip arthroplasty (THA). When an implant is introduced, it will carry a portion of
the load, causing a reduction of stress in some regions of the remaining bone.
This phenomenon is commonly known as stress shielding. In response to the changed
mechanical environment the shielded bone will remodel according to Wolff's law,
resulting in a loss of bone mass through the biological process called
resorption. Resorption can, in turn, cause or contribute to loosening of the
prosthesis. The problem is particularly common among younger THA recipients. This
study explores the hypothesis that through redesign, a total hip prosthesis can
be developed to substantially reduce stress shielding. First, we describe the
development of a new femoral hip prosthesis designed to alleviate this problem
through a new geometry and system of proximal fixation. A numerical comparison
with a conventional intramedullary prosthesis as well as another proximally fixed
prosthesis, recently developed by Munting and Verhelpen (1995. Journal of
Biomechanics 28(8), 949-961) is presented. The results show that the new design
produces a more physiological stress state in the proximal femur.
PMID- 11006391
TI - The mechanical environment of the chondrocyte: a biphasic finite element model of
cell-matrix interactions in articular cartilage.
AB - Mechanical compression of the cartilage extracellular matrix has a significant
effect on the metabolic activity of the chondrocytes. However, the relationship
between the stress-strain and fluid-flow fields at the macroscopic "tissue" level
and those at the microscopic "cellular" level are not fully understood. Based on
the existing experimental data on the deformation behavior and biomechanical
properties of articular cartilage and chondrocytes, a multi-scale biphasic finite
element model was developed of the chondrocyte as a spheroidal inclusion embedded
within the extracellular matrix of a cartilage explant. The mechanical
environment at the cellular level was found to be time-varying and inhomogeneous,
and the large difference ( approximately 3 orders of magnitude) in the elastic
properties of the chondrocyte and those of the extracellular matrix results in
stress concentrations at the cell-matrix border and a nearly two-fold increase in
strain and dilatation (volume change) at the cellular level, as compared to the
macroscopic level. The presence of a narrow "pericellular matrix" with different
properties than that of the chondrocyte or extracellular matrix significantly
altered the principal stress and strain magnitudes within the chondrocyte,
suggesting a functional biomechanical role for the pericellular matrix. These
findings suggest that even under simple compressive loading conditions,
chondrocytes are subjected to a complex local mechanical environment consisting
of tension, compression, shear, and fluid pressure. Knowledge of the local stress
and strain fields in the extracellular matrix is an important step in the
interpretation of studies of mechanical signal transduction in cartilage explant
culture models.
PMID- 11006392
TI - Intrinsic and extrinsic contributions to the passive moment at the
metacarpophalangeal joint.
AB - The purpose of this investigation was to determine whether the passive range of
motion at the finger joints is restricted more by intrinsic tissues (cross a
single joint) or by extrinsic tissues (cross multiple joints). The passive moment
at the metacarpophalangeal (MP) joint of the index finger was modeled as the sum
of intrinsic and extrinsic components. The intrinsic component was modeled only
as a function of MP joint angle. The extrinsic component was modeled as a
function of MP joint angle and wrist angle. With the wrist fixed in seven
different positions the passive moment at the MP joint of eight subjects was
recorded as the finger was rotated through its range at a constant rate. The
moment-angle data were fit by the model and the extrinsic and intrinsic
components were calculated for a range of MP joint angles and wrist positions.
With the MP joint near its extension limit, the median percent extrinsic
contribution was 94% with the wrist extended 60 degrees and 14% with the wrist
flexed 60 degrees. These percentages were 40 and 88%, respectively, with the MP
joint near its flexion limit. Our findings indicate that at most wrist angles the
extrinsic tissues offer greater restraint at the limits of MP joint extension and
flexion than the intrinsic tissues. The intrinsic tissues predominate when the
wrist is flexed or extended enough to slacken the extrinsic tissues. Additional
characteristics of intrinsic and extrinsic tissues can be deduced by examining
the parameter values calculated by the model.
PMID- 11006393
TI - Mechanical properties of compacted morselized cancellous bone graft using one
dimensional consolidation testing.
AB - Failures of orthopaedic procedures that use morselized cancellous bone (MCB)
graft for load bearing are often due to gross displacement within the graft
material. For this reason the mechanical behavior of MCB must be better
understood. Our purpose is to present a detailed testing methodology for the
mechanical characterization of MCB, and to illustrate how this methodology can be
used to study the influence of water and fat content. Complete one-dimensional
consolidation testing was performed on bovine cancellous bone processed to
represent MCB typically used in surgery (52% water, 31% fat). The one-dimensional
consolidation strain under a stress of 1.09MPa was 30.9% and the confined modulus
was 8.0MPa. The coefficient of consolidation (rate of consolidation) was 2. 2x10(
5)cm(2)/s and the coefficient of secondary strain (steady-state creep rate) was
1.9%. While reducing the water content alone had some influence on properties,
reducing the fat content improved both the static and dynamic behavior. A sample
of MCB which had fat intentionally minimized and a lower overall moisture content
(56% water, 5% fat) demonstrated 23.1% strain, a confined modulus of 9.6MPa, a
coefficient of consolidation of 3.4x10(-3)cm(2)/s, and a coefficient of secondary
strain of 0.9%. The test methods described in this technical note can be used to
evaluate the influence of fluid content on the mechanical behavior of MCB.
PMID- 11006394
TI - Chronic softening of cartilage without thickening of underlying bone in a joint
trauma model.
AB - We have recently developed a trauma model to study degradation of the rabbit
patello-femoral joint. Our current working hypothesis is that alterations in
retropatellar cartilage and underlying bone in our model are initiated
independently by acute overstresses developed in each tissue during blunt insult
to the joint, and that the processes of chronic degradation in each tissue are
not related in a mechanical sense. The current study was conducted in an attempt
to help validate our hypothesis by impacting the patello-femoral joint with a
padded interface. Based upon earlier human cadaver experiments, we believe this
would reduce the acute overstresses in patellar bone while the stresses developed
in the overlying retropatellar cartilage would be sufficient enough to initiate a
chronic softening of the tissue. Twenty-four animals received an impact to the
patello-femoral joint and were sacrificed at either 0, 4.5, or 12 months post
insult. Three acute animals were impacted to develop a simplified computational
model to estimate the stresses in joint tissues. The study showed there was a
significant softening of the retropatellar cartilage at 4.5 and 12 months post
trauma, compared to unimpacted controls. However, no thickening of the underlying
subchondral bone was documented at any timepoint. This was consistent with a
reduction of stress in the bone compared to earlier studies, which document
thickened subchondral bone post-insult at the same applied impact load. In
conclusion, this study helped validate our hypothesis by documenting chronic
softening of cartilage without remodeling of the underlying subchondral bone.
Furthermore, this study, along with our earlier studies, suggest that impact load
alone, which is currently used by the automobile industry to certify new
automobiles, is not a good predictor of chronic injuries to a diarthrodial joint,
and that simply the addition of padding to impact interfaces may not be adequate
to protect occupants from chronic injuries.
PMID- 11006395
TI - Comparison of different calculations of three-dimensional joint kinematics from
video-based system data.
AB - When skin-fixed marker trajectories are used to calculate 3D joint kinematics,
the measurement errors (i.e. the difference between the trajectories of the
external markers and those of the skeleton) influence to some extent the accuracy
of the results, depending both on the calculation method and on the axes about
which the rotations are expressed. The purpose of this paper is to compare
several expressions of joint angular variations. Two kinematic concepts are used
to calculate the changes in the orientation of the distal segment versus the
proximal one: the first method consists of computing the components of the
spatial attitude vector, the second one deals with the determination of
elementary rotations about successive axes. For each of these methods, two sets
of three axes are tested to express the results: the axes forming the reference
frame affixed to the body segment adjacent to the joint (named fixed axes), and a
set consisting of a first axis belonging to the proximal segment, a third axis
belonging to the distal segment and a second (floating) axis defined as the cross
product between the two other ones (named mobile axes). To compare these four
distinct expressions on the knee joint, numerical simulations of perturbed skin
marker trajectories are performed, based on experimental data recorded by a
Motion Analysis system during a normal gait cycle. A significant difference is
pointed out only for the internal-external rotation angle, for which the best
expression - from the viewpoint of sensitivity to experimental errors - is
obtained using the components of the attitude vector in a segment-embedded
reference frame.
PMID- 11006396
TI - An empirical approach to characterizing trunk muscle coactivation using
simulation input modeling techniques.
AB - Accurately describing trunk muscle coactivation is fundamental to quantifying the
spine reaction forces that occur during lifting tasks and has been the focus of a
great deal of research in the spine biomechanics literature. One limitation of
previous approaches has been a lack of consideration given to the variability in
these coactivation strategies. The research presented in this paper is an
empirical approach to quantifying and modeling trunk muscle coactivation using
simulation input modeling techniques. Electromyographic (EMG) data were collected
from 28 human subjects as they performed controlled trunk extension exertions.
These exertions included isokinetic (10 and 45 degrees /s) and constant
acceleration (50 degrees /s/s) trunk extensions in symmetric and asymmetric (30
degrees ) postures at two levels of trunk extension moment (30 and 80Nm). The EMG
data were collected from the right and left pairs of the erector spinae,
latissimus dorsi, rectus abdominis, external obliques and internal obliques. Each
subject performed nine repetitions of each combination of independent variables.
The data collected during these trials were used to develop marginal
distributions of trunk muscle activity as well as a 10x10 correlation matrix that
described how the muscles cooperated to produce these extension torques. These
elements were then combined to generate multivariate distributions describing the
coactivation of the trunk musculature. An analysis of these distributions
revealed that increases in extension moment, extension velocity and sagittal
flexion angle created increases in both the mean and the variance of the
distributions of the muscular response, while increases in the rate of trunk
extension acceleration decreased both the mean and variance of the distributions
of activity across all muscles considered. Increases in trunk asymmetry created a
decrease in mean of the ipsi-lateral erector spinae and an increase in the mean
of all other muscles considered, but there was little change in the variance of
these distributions as a function of asymmetry.
PMID- 11006397
TI - A method for measuring endpoint stiffness during multi-joint arm movements.
AB - Current methods for measuring stiffness during human arm movements are either
limited to one-joint motions, or lead to systematic errors. The technique
presented here enables a simple, accurate and unbiased measurement of endpoint
stiffness during multi-joint movements. Using a computer-controlled mechanical
interface, the hand is displaced relative to a prediction of the undisturbed
trajectory. Stiffness is then computed as the ratio of restoring force to
displacement amplitude. Because of the accuracy of the prediction (< 1 cm error
after 200 ms) and the quality of the implementation, the movement is not
disrupted by the perturbation. This technique requires only 13 as many trials to
identify stiffness as the method of Gomi and Kawato (1997, Biological Cybernetics
76, 163-171) and may, therefore, be used to investigate the evolution of
stiffness during motor adaptation.
PMID- 11006398
TI - The position of the rotation center of the glenohumeral joint.
AB - To validate the assumption that the center of rotation in the glenohumeral (GH)
joint can be described based on the geometry of the joint, two methods for
calculation of the GH rotation center were compared. These are a kinematic
estimation based on the calculation of instantaneous helical axes, and a
geometric estimation based on a spherical fit through the surface of the glenoid.
Four fresh cadaver arms were fixed at the scapula and fitted with electromagnetic
sensors. Each arm was moved in different directions while at the same time the
orientation of the humerus was recorded. Subsequently, each specimen was
dissected and its glenoid and humeral head surfaces were digitized. Results
indicate no differences between the methods. It is concluded that the method to
estimate the GH center of rotation as the center of a sphere through the glenoid
surface, with the radius of the humeral head, appears to be valid.
PMID- 11006399
TI - High-precision satellite positioning system as a new tool to study the
biomechanics of human locomotion.
AB - New Global Positioning System (GPS) receivers allow now to measure a location on
earth at high frequency (5Hz) with a centimetric precision using phase
differential positioning method. We studied whether such technique was accurate
enough to retrieve basic parameters of human locomotion. Eight subjects walked on
an athletics track at four different imposed step frequencies (70-130steps/min)
plus a run at free pace. Differential carrier phase localization between a fixed
base station and the mobile antenna mounted on the walking person was calculated.
In parallel, a triaxial accelerometer, attached to the low back, recorded body
accelerations. The different parameters were averaged for 150 consecutive steps
of each run for each subject (total of 6000 steps analyzed). We observed a
perfect correlation between average step duration measured by accelerometer and
by GPS (r=0.9998, N=40). Two important parameters for the calculation of the
external work of walking were also analyzed, namely the vertical lift of the
trunk and the velocity variation per step. For an average walking speed of
4.0km/h, average vertical lift and velocity variation were, respectively, 4.8cm
and 0.60km/h. The average intra-individual step-to-step variability at a constant
speed, which includes GPS errors and the biological gait style variation, were
found to be 24. 5% (coefficient of variation) for vertical lift and 44.5% for
velocity variation. It is concluded that GPS technique can provide useful
biomechanical parameters for the analysis of an unlimited number of strides in an
unconstrained free-living environment.
PMID- 11006400
TI - Hysteresis measurements in intact human tendon.
AB - Mechanical hysteresis in tendons has traditionally been quantified from tensile
testing of isolated specimens. Limitations associated with tendon displacement
measurement and clamping, and uncertainties as to whether in vitro material
represents intact tendon function necessitate measuring hysteresis under in vivo
conditions. In the present study such measurements were taken in the human
tibialis anterior (TA) tendon. Having the foot fixed on a dynamometer footplate,
the displacement of the TA tendon during stimulation and relaxation of the TA
muscle was recorded by means of ultrasonography in six men. Combining moment data
corresponding to 0, 20, 40, 60, 80 and 100% of maximum voltage moment and the
respective tendon-displacement data, a hysteresis loop was obtained between the
load-displacement curves during contraction and relaxation. Measurement of the
hysteresis loop area yielded a value of 19%. This value agrees with results from
in vitro tensile tests of low-stress tendons, suitable for tensile force
transmission and joint displacement control. In fact, the human TA tendon has
such functional characteristics. The methodology presented allows design of
longitudinal and cross-sectional experimental protocols, and in vivo assessment
of tendon function and propensity to overheat.
PMID- 11006401
TI - On the independence of time and strain effects in the stress relaxation of
ligaments and tendons.
AB - The hypothesis of variables separation, namely the time and the strain separation
in the relaxation function, is widely used in soft tissue biomechanics. Although
this hypothesis is central to several biomechanical models, only few experimental
works have tried to verify it. From these studies, contradictory results have
been found. Moreover, it has recently been noted that no such experimental
verification has been performed for ligament tissues. In this paper, an
experimental method is developed to test the hypothesis of variables separation.
This method is then used with human cruciate ligaments and patellar tendons. It
is shown that the use of the variables separation hypothesis is justified at
least for strain values lower than 16% for anterior cruciate ligament, lower than
12% for posterior cruciate ligament and lower than 6% for patellar tendon. The
method presented in this paper could be used to verify the validity of variables
separation for other tissues.
PMID- 11006402
TI - Postural control of trunk during unstable sitting.
AB - A method for quantifying postural control of the lumbar spine during unstable
sitting was developed. The unstable seat apparatus was equipped with leg and foot
supports to isolate the control of the lumbar spine and trunk from the
adjustments in the lower body joints. Polyester resin hemispheres with decreasing
diameters were attached to the bottom of the seat to achieve increasing levels of
task difficulty. The seat was placed on a force plate at the edge of a table and
the participating subjects were instructed to maintain their balance while
sitting on the seat. Coordinates of center of pressure (CoP) were recorded and
quantified with summary statistics and random walk analysis. The CoP movement
increased significantly with increased seat instability (task difficulty)
(p<0.01). Stabilogram plots of the CoP movement revealed short and long-term
regions consistent with the hypothesis that the two regions reflect open and
closed-loop postural control mechanisms. Repeatability of the CoP parameters was
excellent for the summary statistics and the short-term random walk coefficients
(0.77
or = 4-fold over vehicle control, in all studies. These data demonstrate the
reproducibility of positive control response in MN assay in our laboratory and
support the MN Assay Expert Panel's view that the use of positive control may not
be necessary in every study.
PMID- 11006412
TI - Mutation spectra in Salmonella of analogues of MX: implications of chemical
structure for mutational mechanisms.
AB - We determined the mutation spectra in Salmonella of four chlorinated butenoic
acid analogues (BA-1 through BA-4) of the drinking water mutagen 3-chloro-4
(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and compared the results with
those generated previously by us for MX and a related compound, MCF. We then
considered relationships between the properties of mutagenic potency and
mutational specificity for these six chlorinated butenoic acid analogues. In
TA98, the three most potent mutagens, BA-3, BA-4, MX, and the organic extract,
all induced large percentages of complex frameshifts (33-67%), which distinguish
these agents from any other class of compound studied previously. In TA100, which
has only GC sites for mutation recovery, >71% of the mutations induced by all of
the agents were GC-->TA transversions. The availability of both GC and TA sites
for mutation in TA104 resulted in greater distinctions in mutational specificity
than in TA100. MX targeted GC sites almost exclusively (98%); the structurally
similar BA-4 and BA-2 produced mutations at similar frequencies at both GC and AT
sites; and the structurally similar BA-3 and BA-1 induced most mutations at AT
sites (69%). Thus, large variations in structural properties influencing relative
mutagenic potency appeared to be distinct from the more localized similar
structural features influencing mutagenic specificity in TA104. Among a set of
physicochemical properties examined for the six butenoic acids, a significant
correlation was found between pK(a) and mutagenic potency in TA100, even when the
unionized fraction of the activity dose was considered. In addition, a
correlation in CLOGP for BA-1 to BA-4 suggested a role for bioavailability in
determining mutagenic potency. These results illustrate the potential value of
structural analyses for exploring the relationship between chemical structure and
mutational mechanisms. To our knowledge, this is the first study in which such
analyses have been applied to structural analogues for which both mutagenic
potency and mutation spectra date were available.
PMID- 11006413
TI - Minisatellite mutation frequency in human sperm following radiotherapy.
AB - Screening pedigrees for inherited minisatellite length changes provides an
efficient means of monitoring repeat DNA instability but has given rise to
apparently contradictory results regarding the effects of radiation on the human
germline. To explore this further in individuals with known radiation doses and
to potentially gain information on the timing of mutation induction, we have used
an extremely sensitive single molecule approach to quantify the frequencies of
mutation at the hypervariable minisatellites B6.7 and CEB1 in the sperm of three
seminoma patients following hemipelvic radiotherapy. Scattered radiation doses to
the testicles were monitored and pre-treatment sperm DNA was compared with sperm
derived from irradiated pre-meiotic, meiotic and post-meiotic cells. We show no
evidence for mutation induction in any of the patients and discuss this finding
in the context of previous population studies using minisatellites as reporter
systems, one of which provided evidence for radiation-induced germline mutation.
PMID- 11006414
TI - DNA breakage detection-FISH (DBD-FISH) in human spermatozoa: technical variants
evidence different structural features.
AB - Non-irradiated and X-irradiated (80 Gy) human spermatozoa were processed for in
situ DNA breakage detection-FISH (DBD-FISH) of the whole genome, following two
alternative variations of the basic technique. In the first, cells were initially
incubated in the alkaline unwinding solution for transformation of DNA breaks
into single-stranded DNA (ssDNA) to be hybridized, followed by the lysing
solutions for protein removal. In the second, incubation in the lysing solutions
was carried out before the denaturation step. The first approach yielded two
subpopulations. While most sperm nuclei were faintly labeled and had
chromocenters, a small subpopulation was strongly and homogeneously labeled, due
to extensive DNA breakage. X-ray exposure increased the surface and mean
fluorescence intensity. Otherwise, when the denaturation step was performed after
protein extraction, all sperm nuclei yielded strong and dispersed FISH signals.
Protein removal allows access of the unwinding solution to the DNA, which has
abundant alkali-labile sites, and thus gives rise to large areas of ssDNA that
are labeled by FISH. X-ray exposure increased the dispersion of FISH signals but
decreased their mean fluorescence intensity. A linear dose-response was generated
using the second experimental variant, being 30 Gy the lowest dose for detecting
induction of damage by X-rays in mature sperm chromatin. These results indicate
that DBD-FISH is not only useful for in situ detection of DNA breakage but also
for revealing structural features of chromatin.
PMID- 11006415
TI - DNA breakage detection-fish (DBD-FISH): effect of unwinding time.
AB - DBD-FISH is a new procedure that allows detection and quantification of DNA
breakage in situ within specific DNA target sites. Cells embedded in an agarose
matrix on a slide are treated in an alkaline unwinding solution to transform DNA
breaks into single-stranded DNA (ssDNA). After removal of proteins, DNA probes
are hybridized and detected. DNA breaks increase the ssDNA and relax supercoiling
of DNA loops, so more probe hybridizes, thereby increasing the surface area and
fluorescence intensity of the FISH signal. The probe selects the chromatin area
to be analysed. In order to restrict the extension of unwound ssDNA to a region
closer to the origin of the DNA break, human leukocytes were processed for DBD
FISH with a whole genome probe, after a 10 Gy dose of X-rays, for various
unwinding times: 5, 2 min and 30s. Two cell populations were detected after 30s,
but not with the 5 or 2 min unwinding times. One cell group had small to medium
haloes corresponding to the relaxation of DNA supercoiling after DAPI staining,
and strong DBD-FISH labelling of induced DNA breaks, whereas the other cell group
showed big haloes of DNA loop unfolding and an absence of DBD-FISH labelling. The
latter group was similar to cells processed by DBD-FISH without the unwinding
step. Thus, they should correspond to cells unaffected by the alkaline unwinding
solution, possibly because very brief unwinding times do not allow the diffusion
of the alkali into the cells deep within the gel, thus biasing the results.
Taking this into account, 2 min seems to be the minimum unwinding time required
for an accurate detection of a signal by DBD-FISH.
PMID- 11006416
TI - DNA damage in rat lymphocytes treated in vitro with iron cations and exposed to 7
mT magnetic fields (static or 50 Hz).
AB - The present study was undertaken to verify a hypothesis that exposure of the
cells to static or 50 Hz magnetic fields (MF) and simultaneous treatment with a
known oxidant, ferrous chloride, may affect the oxidative deterioration of DNA
molecules. The comet assay was chosen for the assessment of DNA damage. The
experiments were performed on isolated rat lymphocytes incubated for 3h in
Helmholtz coils at 7 mT static or 50 Hz MF. During MF exposure, part of the cell
samples were incubated with 0.01 microM H(2)O(2) and another one with 10
microg/ml FeCl(2,) the rest serving as controls. Lymphocyte exposure to MF at 7
mT did not increase the number of cells with DNA damage in the comet assay.
Incubation of lymphocytes with 10 microg/ml FeCl(2) did not produce a detectable
damage of DNA either. However, when the FeCl(2)-incubated lymphocytes were
simultaneously exposed to 7 mT MF, the number of damaged cells was significantly
increased and reached about 20% for static MF and 15% for power frequency MF. In
the control samples about 97% of the cells did not have any DNA damage. It is not
possible at present to offer a reasonable explanation for the findings of this
investigation - the high increase in the number of lymphocytes showing symptoms
of DNA damage in the comet assay, following simultaneous exposure to the
combination of two non-cytotoxic factors -10 microg/ml FeCl(2) and 7 mT MF. In
view of the obtained results we can only hypothesise that under the influence of
simultaneous exposure to FeCl(2) and static or 50 Hz MF, the number of reactive
oxygen species generated by iron cations may increase substantially. Further
studies will be necessary to confirm this hypothesis and define the biological
significance of the observed effect.
PMID- 11006418
TI - Corrigendum to "Congenital abnormalities and indicators of germinal mutations in
the vicinity of an acrylonitrile producing factory"
PMID- 11006417
TI - High plating density improves Big Blue system efficiency without loss of
sensitivity.
AB - To increase efficiency in the Big Blue system, the plating density was increased
from 15000 to 30000 or 45000 plaque forming units (pfus) per plate by increasing
the density of the E. coli lawn and decreasing individual plaque size. Small
plaque size ensured minimal overlap of the plaques. Liver from one 3- and one 25
month-old mouse (low and high mutation frequencies, respectively) was analyzed
and neither plating density nor plaque size affected mutant/mutation frequency
and pattern. The color intensity of particular mutant plaques was not affected by
plaque size or plating density. Optimal sensitivity is achieved by sequencing
mutants to calculate the mutation frequency from the mutant frequency and to
identify altered patterns of mutation. Detailed effort and cost accounting of the
Big Blue system (including mouse handling, DNA extraction, plaque screening,
plaque purification, and DNA sequencing) reveals that one-quarter of the total
effort is devoted to plating and screening of plates. This effort is reduced two
fold with high plating density. The total cost of the Big Blue system is reduced
by 17%. The total cost of the High Plating Density Big Blue system is now only
12% more costly than a selectable assay and offers an extensively validated
system with a large mutation database representing a decade of effort.
PMID- 11006419
TI - Detection of novelty by perinatal rats.
AB - This study investigated the development of fetal/neonatal rats' ability to
distinguish between a novel and familiar taste. Here, we report that neonatal
rats alter their orofacial movements (e.g., mouth movements and licks) upon
tasting saccharin (SAC) if it was experienced previously. We also sought to
determine the origins and duration of this response. Fetuses of embryonic ages
E17, E18, or E19 received an oral injection of 10 microL 0.3% SAC while in utero.
These animals were then reexposed to SAC on postnatal day 3, (P3) and
observations of orofacial motor responses were recorded. Only neonates that first
experienced SAC on E19 exhibited a SAC-induced stimulation of mouthing and
licking on P3. These data suggested that a taste-recognition memory (TRM) is
maintained for up to 5 days (i.e., E19 to P3). However, in this paradigm, the
youngest fetuses also have the longest retention interval. Could these data also
reflect the limitations of the E17 and E18 fetuses in retaining the TRM? In a
second study, we shortened the taste exposure-reexposure interval to 2 days in an
attempt to detect the TRM in younger fetuses. As expected, E19 rats exhibited a
TRM when tested on E21. However, neither the E17 nor E18 fetuses showed SAC
induced increases in mouthing and licking when tested 2 days after their initial
exposure (E19 or E20). Finally, in order to determine whether a TRM could be
detected in fetuses as well as neonates (see above), we conducted an additional
study wherein E21 fetuses were tested before parturition. Like E21 neonates, E21
rat fetuses that had received SAC on E19 showed a differential response to SAC
depending on whether it was novel or familiar. Thus, although E21 fetal orofacial
movements were less frequent than those of the E21 neonate, the fetal-testing
procedures were not sufficient to obscure the detection of a TRM. In summary, the
data indicate that E19 rat fetuses can acquire a TRM and retain it for at least 2
5 days, whereas E17 and E18 fetuses cannot.
PMID- 11006420
TI - Entrainment of the rat motor activity rhythm: effects of the light-dark cycle and
physical exercise.
AB - The circadian system is believed to be composed of a population of oscillators
that couple together and generate a single rhythm. If this coupling is not strong
enough, the circadian system can be dissociated into two or more groups of
oscillators, and this is manifested in a dissociation of the overt rhythm into at
least two circadian components. This study aims to examine the influence of
factors, such as the difference in impact between T and tau, light intensity, and
access to a running wheel, on the distribution of motor activity throughout the
light-dark (LD) cycle and the dissociation of the rhythm. Rats were submitted to
LD cycles of 23 h (T23) or 25 h. For each such cycle, half the rats were
submitted to high light intensity and the other half to low light intensity. For
each of these conditions, half the rats were kept in small cages, and the other
half were in cages with a running wheel. Rats were maintained first under LD
cycles and afterwards under constant darkness (DD). Motor activity was recorded
throughout the whole experiment by means of activity meters with infrared beams.
Results show that the distribution of motor activity throughout the cycle and the
after effects observed in the rhythm under DD depended on light intensity and
access to the wheel. Moreover, under T23, some rats showed two simultaneous
circadian components whose manifestation also depended on the experimental
conditions. The results indicate that the strength of circadian entrainment to LD
cycles in the rat depends on three factors: the period length of the LD cycle,
light intensity used during the light phase, and access to a running wheel.
PMID- 11006421
TI - Evaluation of two rodent delayed-response memory tasks: a method with retractable
levers versus a method with closing doors.
AB - The purpose of this study was to evaluate and compare two similar rodent memory
tasks developed in our laboratory that employ stimulus discrimination and delayed
response (light and tone stimuli and variable length delays) and to determine
their sensitivity to the muscarinic-acetylcholine receptor (mAChR) antagonist,
scopolamine hydrobromide (SCOP HBr), and its quaternary (methylbromide) analog
(SCOP MBr). Male Wistar rats were trained in either an open chamber that employed
retracting levers (RLM) during the delays, or a method that utilized closing
doors (CDM) that separated the rats from the levers during delays to reduce
positional (nonmnemonic) strategies. When the rats were well trained, dose-effect
studies (microg/kg doses, s.c., 30 min before test sessions) of SCOP HBr or MBr
were performed. Baseline performance was characterized by delay-dependent
decreases in accuracy in both methods except when the tone was the stimulus in
the RLM. SCOP HBr impaired performance in both tasks at the higher doses tested,
although the effects were more consistent in the CDM task and accuracy associated
with each stimulus was affected similarly. Surprisingly, SCOP MBr also impaired
performance of each task, especially when the tone was the stimulus, while
accuracy associated with the light was not affected in the CDM task. Overall, the
results indicated that the CDM was a somewhat more reliable task, appearing to
reduce positional strategies with less variability in response to the mAChR
antagonists, although some stimulus-modality specific effects were noted. It also
appears important to consider the peripheral effects of mAChR antagonists (and
potential central effects of quaternary mAChR antagonists) when interpreting
results from behavioral studies, especially those involving conditional
discrimination and delayed response.
PMID- 11006422
TI - Microinfusion of nefazodone into the basolateral nucleus of the amygdala enhances
defensive behavior induced by NMDA stimulation of the inferior colliculus.
AB - The inferior colliculus is notably associated with defensive behavior. Electrical
or pharmacological stimulation of the inferior colliculus induces aversive
reactions such as running and jumping. Lesion of the basolateral nucleus of the
amygdala decreases the threshold of aversive reactions induced by electrical
stimulation of the inferior colliculus. The present work examined the influence
of microinjections of nefazodone, a serotonin (5-HT(2)) antagonist, into the
basolateral nucleus of amygdala on aversive reactions induced by N-methyl-D
aspartate (NMDA) microinjected into the inferior colliculus. Rats implanted with
cannulae in the inferior colliculus and in the basolateral nucleus of the
amygdala were submitted to the open-field test where defensive behaviors were
observed. Results indicated that microinjection of nefazodone into the
basolateral nucleus of the amygdala increases aversive responses induced by NMDA
injections into the inferior colliculus. This result suggests that the inferior
colliculus and the basolateral nucleus of the amygdala have a functional
relationship on the neural circuitry of defensive behavior. Moreover, 5-HT(2)
receptors located at the basolateral nucleus of the amygdala seem to play an
inhibitory role on defensive behaviors induced by inferior colliculus
stimulation.
PMID- 11006423
TI - Effect of photoperiod on body weight gain, and daily energy intake and energy
expenditure in Japanese quail (Coturnix c. japonica).
AB - Effect of photoperiod and food duration on body weight gain, energy intake,
energy expenditure, and sexual development were investigated in two strains of
Japanese quail (Coturnix c. japonica), bred for meat (broilers) or egg production
(layers), from 7 to 71 days of age. In a first experiment chicks were subjected
to 18L:6D, 15L:9D, 12L:12D, 9L:15D, or 6L:18D, with ad lib food during the light
period. In a second experiment birds were exposed to a long photoperiod (18L:6D
or 15L:9D) with ad lib food during part of the light period (first 6 or 9 h,
respectively). Longer photoperiods were associated with larger weight gains. In
18L:6D broilers total body weight gain was 262 g compared to 213 g in 6L:18D
broilers. In layers, corresponding values were 182 and 131 g. This effect of
photoperiod on weight gain was primarily due to the effect of photoperiod on food
availability. The photoperiod below which detrimental effects on weight gain
occurred was 9L:15D for both strains. Chicks subjected to 9L:15D or 6L:18D
exploited crop filling to enhance energy intake. They also decreased nocturnal
metabolic rates to a greater extent compared to levels during the light phase
than chicks subjected to light periods of 12 h or more. Sexual maturation was
stimulated by photoperiod. At the age of 71 days, eight out of nine females
subjected to 18L:6D were producing eggs, but none of the 6L:18D females. It is
concluded that changes in feeding behavior and energy expenditure shown under
short photoperiods are part of a strategy that allow chicks to gain weight
continuously.
PMID- 11006424
TI - Selective depletion of bacteria alters but does not eliminate odors of
individuality in Rattus norvegicus.
AB - To determine if odors of individuality are influenced by the removal of Gram
negative or Gram-positive gut bacteria, Long-Evans rats were trained in an
operant olfactometer to discriminate between the odors of two individual
conspecifics and their operant responses to three different odors in randomly
presented probe trials were analyzed. Significantly more responses were made to
the probe odors from two known individuals than to the probe odors from known
individuals with their Gram-negative bacteria eliminated (Experiment 1) or their
Gram-positive bacteria eliminated (Experiment 2). Responses to the probe odors
from known rats with bacterial selectively depleted did not differ significantly
from responses to probe odors from unknown rats. These results support the
hypothesis that the urinary odor of an individual rat is altered by the removal
of specific gut bacteria. In Experiments 3 and 4, subjects made fewer errors in
learning to discriminate between the odors of the familiar rats whose bacteria
had been selectively depleted than between the odors of unknown rats. This
"savings effect" indicates that some components of the individual urinary odors
were retained after the removal of specific gut bacteria. Thus, the eliminated
bacteria were not totally responsible for the odors of individuality. The outcome
of Experiments 3 and 4 also indicates that conclusions regarding the recognition
of odors by rats should not be made on the outcome of probe trial experiments
alone.
PMID- 11006425
TI - Restraint stress augments antibody production in cyclophosphamide-treated mice.
AB - These studies evaluated the effects of a psychological stressor (restraint, RST)
on antibody production in male BALB/cByJ mice. In Experiment 1, mice were
immunized with keyhole limpet hemocyanin (KLH, 100 microg i.p.) 8 h prior to 15 h
of RST or food and water deprivation (FWD). RST mice exhibited higher serum anti
KLH IgM and IgG antibodies than FWD mice. In Experiment 2, mice were given either
cyclophosphamide (CY, 15 mg/kg) or saline (SAL) prior to immunization with KLH
and RST or FWD. ANOVA revealed serum anti-KLH IgG antibody titers in CY+RST
animals to be significantly higher than in CY+FWD, SAL+FWD, and SAL+RST mice.
Anti-KLH IgM titers of CY+RST mice were higher than those of other groups before
and after a second immunization with KLH. In Experiment 3, we show that these
changes in antibody production are not likely to be mediated via CY-induced
alterations in the reactivity of the hypothalamo-pituitary-adrenal axis to RST.
Together, these results indicate two potentially immunomodulatory parameters (RST
and CY) can interact to alter a humoral immune response. In addition, these data
support the hypothesis that humoral immune response of mice can be more reactive
to stress when the mice are given a low dose of an immunomodulatory drug prior to
stressor exposure.
PMID- 11006426
TI - The impact of milk-derived unconditioned and conditioned negative feedback on the
microstructure of ingestive behavior.
AB - We describe at the microstructural level the impact of unconditioned and
conditioned negative feedback on the licking behavior of the rat. Six groups of
rats were trained to ingest one of six different dilutions of sweetened milk
(0.5:1, 1:1, 2:1, 4;1, 8:1, and 16:1, water to milk ratios) under real feeding
conditions until intake was stable. Then they were given five sham-feeding tests
with the same solution. We compared the size of the clusters (SC) and their
number (NC) during the 15-min period when intake rate was declining in the real
feeding test with SC and NC during the corresponding 15-min period in the
following sham-feeding test. Intake increased significantly over the five sham
feeding tests with the two highest concentrations, indicating the extinction of
conditioned negative feedback. With these two solutions, we compared the
microstructure of licking behavior in the first with that in the fifth sham
feeding test to determine if conditioned negative feedback affected SC or NC or
both. The effect of both unconditioned and conditioned negative feedback on
licking behavior was to decrease the number of clusters without affecting their
size. We conclude that negative feedback derived from the accumulation of milk in
the gastrointestinal tract decreases the probability of initiating a bout of
licking during a pause. It has no effect on the ability to continue a bout of
licking once it has begun.
PMID- 11006427
TI - Attention to metabolic hunger and its effects on Helicobacter pylori infection.
AB - A significant decrease in the bacterial count of small intestinal mucosa has been
observed in children with recurrent diarrhea or abdominal pain in the time that
has elapsed from the previous meal. Humans may be trained to recognize metabolic
feelings of hunger that are associated with a steady and slightly lower glycemia
than baseline, between 4.7 and 3.9 mmol/L (intervention). An eating habit
associated with a decrease in preprandial glycemia prevented diarrhea relapses,
and was expected to impair intestinal microflora growth, including Helicobacter
pylori in the stomach. The development of Helicobacter pylori infection might be
prevented during childhood, and recovery from infection may be expected with
intervention. The improvement in attention to metabolic feelings consisted of
acquiring a predictive ability of glycemia by distinction between unsolicited
hunger feelings (metabolic hunger) and those associated with external cues.
Matching intake to the inbetween energy needs served to predict the subsequent
emergence of the metabolic hunger. The matching was further compensated for the
early or late emergence of metabolic hunger at the subsequent meals. Fruit and
vegetables were increased to avoid abrupt glycemia lowering. This intervention
was trained in 5-month periods. Subjects (209, 44, and 58) completed their
training during 4-year periods between 1982 and 1994, and were enrolled in a
prospective, controlled, randomized, interventional, preventive, and cohort
study. The "prevention" hypothesis was tested in a subgroup of 86 healthy infants
who were recalled in the years 1996 to 1998. A "recovery" study of approximately
a 1-year intervention was investigated in 47 healthy subjects between ages 5 and
25, who were positive for anti-H. pylori and had no need for an immediate
antibiotic treatment at entry. The following behavioral factors were recorded in
a 7-day home diary and calculated: the fraction of meals induced by metabolic
hunger out of 21 main mealtimes; average preprandial glycemia (DAP glycemia);
daily intakes, activity; and bedtime hours. The decrease in preprandial glycemia
was the objective measure of compliance with the recognition of "metabolic"
hunger. Anthropometric measures and blood tests were obtained for nutritional and
functional verifications. Average preprandial glycemia was 8.5 and 8.6% lower in
the intervention groups than the control groups in the "prevention" and
"recovery" studies, respectively, at the end of follow-up (p<0.05 and <0.001,
respectively). A 4.7% seroprevalence of H. pylori infection was observed in the
intervention group, with 30.2% in the control group at a mean age of 10 years
after approximately an 8-year follow-up in the "prevention" study (p<0.0005). The
seroprevalence decreased to 9 of 24 (37.5%) under intervention as opposed to 20
of 23 controls (87%) in the recovery study (p<0.002). A significant positive
correlation was found between DAP glycemia and the anti-H. pylori serum antibody
concentration (r = 0.52; p = 0.0002). A decrease in the level of immune
stimulation by H. pylori infection was observed due to the intervention, which
may have a preventive and therapeutic role on the infection.
PMID- 11006428
TI - The relationship between audiogenic seizure (AGS) susceptibility and forebrain
tone-responsiveness in genetically AGS-prone Wistar rats.
AB - The present study characterized the intensity-response functions of extracellular
field responsiveness of different cortical/subcortical structures of the
forebrain following the free-field presentation of tone stimuli, within a
population of genetically audiogenic seizure (AGS)-prone KM-Wistar rats. The
neural response properties of each case were compared to its propensity to
exhibit AGSs during the continuous tone stimulation (15 kHz, 90 s at max.). The
amplitudes or slope components of the evoked responses and their peak latencies
showed significant positive (amplitude and slope) and negative (peak latency)
Bolzmann's sigmoid relationships with the onset-latency of AGS. These
relationships, with areal differences in the slopes of saturation functions,
applied for the three different data sets recorded simultaneously from the
stratum radiatum dendritic layer of the hippocampal CA1 area, primary auditory
cortex layers II-IV, and frontal cortex surface. In addition, the similar type of
functions between the evoked response variables and AGS onset latency held when
all the areas were considered together. These data suggest that the neural
responsiveness to acoustic stimulation of the primary sensory, multimodal and
association cortices of the forebrain may altogether contribute to the seizure
initiation by that modality in the genetically AGS-prone rats. It has been
previously shown that there exist abundant and dispersed auditory projections
from these forebrain areas to the brain stem and spinal cord, structures that are
generally considered to be the key predisposing factors in the generation of AGS.
Hence, the types of correlation found reflect the subject-specific stage of
forebrain responsiveness, being either related or unrelated to genetic AGS
specific changes, and possibly its triggering impact upon the lower brain AGS
network. Accordingly, the mere comparison of forebrain response measures of these
AGS-prone animals with those of the AGS-resistant ones could not reveal the
result presented.
PMID- 11006429
TI - In two species, females exhibit superior working memory and inferior reference
memory on the water radial-arm maze.
AB - Male and female mice and rats were tested on a water escape version of the radial
arm maze designed to measure working and reference memory. In both species,
females exhibited superior working memory during acquisition, and were better
able to handle a higher memory load. However, male mice and rats exhibited better
reference memory than females during the asymptotic portion of testing. Our data
suggest that females may be better at working memory when both working and
reference memory information must be learned simultaneously, and males better at
reference memory when it has been differentiated from working memory.
PMID- 11006430
TI - The effect of activity history and current activity on static and dynamic
postural balance in older adults.
AB - The purpose of this study was to investigate the effects of former athleticism
and current activity status on static and dynamic postural balance in older
adults. Fifty-six subjects participated in four study groups including former
athletes, currently active (AA; n = 15; 69.1+/-4.4 years.; 77.8+/-9.8 kg), former
athletes, currently inactive (AI; n = 12; 66.7 years.; 87.2+/-15.1 kg), controls
currently active (CA; n = 14; 68.6 +/- 4.5 years.; 73.9+/-15 kg), and controls
currently inactive (CI; n = 15; 72.8+/-4.8 years; 81.1+/-14.8). All subjects were
tested for height, weight, flexibility, thigh circumference, and static
(sharpened Romberg/unipedal stance), and dynamic (step length and width) balance
tests. The sharpened Romberg (eyes open) test showed that AA (60.0+/-0 s) and CA
(59.4+/- 0.5 s) balanced significantly longer than AI (41.5+/-7.2 s), and CI
(41.8+/-6.1 s) (p<0.05). The unipedal (eyes open) test balance scores for AA, CA,
AI, and CI were respectively 40.0+/-4.5, 55.1+/- 3.4, 33.0+/-7.1, and 27.5+/-6.1
s, with CA significantly better than CI (p<0.05). In dynamic balance AA and CA
(746.1+/-28.0 and 724.6+/-24.3 mm) showed significantly longer step lengths
(p<0.05) than CI (643.7+/-26.5 mm). The eyes closed test results for relative
group comparisons were similar. Overall, two-way analysis of variance showed a
significant activity main effect for all dependent variables measured (p<0.05).
The results indicated that current activity status plays a key role on balance
performance in older adults. Furthermore, former athletic activity history
provides no protection for the age related onset of postural imbalance.
PMID- 11006431
TI - Short-term behavioral and electrophysiological consequences of underwater trauma.
AB - In a previous work we found that a 30-s underwater trauma, following 8 days of
training for a spatial memory task in the water maze, resulted in poor
performance in the spatial memory task at both 1 h and 3 weeks after the trauma.
Here we found that compared with naive animals and animals that were trained for
the spatial learning task but were not traumatized, the traumatized rats showed
impaired performance in a spatial learning task in the water maze 20 min after
the trauma and a reduced level of dentate gyrus long-term potentiation (LTP) 40
min after high-frequency stimulation to the perforant path. We also found a
positive correlation between the behavioral performance and hippocampal
plasticity. The reduced ability to induce LTP suggests that the trauma-related
behavioral impairment is mediated by hippocampal-dependent processes. The
underwater trauma may provide an important and potentially powerful model for
understanding the mechanisms underlying the relationship between stress,
cognition, and learning.
PMID- 11006432
TI - Effects of food on cortisol and mood in vulnerable subjects under controllable
and uncontrollable stress.
AB - The aim of this study was to investigate whether in stress-prone subjects,
carbohydrate-rich, protein-poor food (CR/PP) diminished depressive mood and a
cortisol response under controllable as well as uncontrollable laboratory stress.
Twenty-two subjects with high stress proneness (HS) and 23 subjects with low
stress proneness (LS) participated in a controllable- and uncontrollable-stress
experiment during either a CR/PP or protein-rich, carbohydrate-poor (PR/CP) diet.
Both controllable and uncontrollable laboratory stress significantly increased
pulse rate and skin conductance in HS and LS subjects, whereas uncontrollable
stress increased feelings of depression, anger, tension, and fatigue and
decreased feelings of vigor. Only in HS subjects, a cortisol response and
feelings of depression became lower under the CR/PP diet condition, irrespective
of the controllability of the laboratory stressor, suggesting an increased
ability to cope with stress. Because the CR/PP diet compared with the PR/CP diet
previously has been found to cause a 42% increase in plasma tryptophan/SigmaLNAA,
seen as an indirect measure of increases in brain serotonin levels, the present
results suggest that an enhanced serotonin function in HS subjects may be
involved.
PMID- 11006433
TI - Palatability and intake relationships in free-living humans. characterization and
independence of influence in North Americans.
AB - In order to investigate palatability influences on the ad lib eating behavior of
free-living humans, 564 participants were paid to maintain food intake diaries
for 7 days. They recorded their intake along with a global rating of the
palatability of the entire meal on a seven-point scale. It was found that most
meals that are self-selected are palatable and that only 9.3% are rated as
unpalatable. Meals that were highest in palatability were 44% larger than meals
that were low in palatability, but palatability only accounted for around 4% of
the variance in meal sizes. Multiple regression demonstrated that palatability
appears to act on intake independent of the levels of other influential factors.
These results were very similar to those observed for the French and suggest that
palatability operates similarly on intake regardless of culture. Palatability
appears to be an influence on the amounts ingested by free-living humans in their
natural environments but appears to be only one of many influential factors and
accounts for only a small proportion of the variance in intake.
PMID- 11006434
TI - Influence of the shape of the experimental room on spatial learning in rats.
AB - Rats and other mammals can orient themselves in their habitat and locate various
goals using different learning strategies. When a cartographic or local strategy
is used, the animals construct and store in their long-term memories a complex
representation of the extramaze space. However, exactly what constitutes the
behaviorally key components of the extramaze space is still little known. The
purpose of this study was to investigate whether the shape of the environment
that surrounds the animal is an informative factor when a cartographic strategy
is used. Two experiments were performed in which the rats were trained to find
food in the goal arm of a four-arm, plus-shaped maze. Experiment 1 shows that
lesions to the hippocampus impair the acquisition of this task, which suggests
that in fact, a cartographic strategy is necessary to solve it. In Experiment 2,
in which only one group of neurologically intact rats was used, we directly
manipulated the shape of the space around the maze. The results showed that once
the animals have learned the task, the hiding of all the extramaze single
landmarks while keeping intact the general shape of the experimental room does
not affect performance. Only when the shape of the surrounding space was modified
did the performance deteriorate significantly. These results are discussed in
relation to the different components of the extramaze environment and the
contribution of each of them to the spatial learning.
PMID- 11006435
TI - Effects of prenatal stress on defensive withdrawal behavior and corticotropin
releasing factor systems in rat brain.
AB - Exposure of pregnant rats to stress results in offspring that exhibit abnormally
fearful behavior and have elevated neuroendocrine responses to novelty and
aversive stimuli. This study examined the effects of prenatal stress on plasma
corticosterone, adrenal weight, defensive withdrawal behavior, and the density of
receptors for corticotropin releasing factor (CRF) in the amygdala. Pregnant
Sprague-Dawley rats were stressed by daily handling and saline injection (s.c.,
0.9%, 0.1 mL) during the last week of gestation. Male offspring were studied at
adulthood (60-120 days of age). Adrenal hypertrophy and increased plasma
corticosterone were observed in the prenatally stressed offspring. Defensive
withdrawal, an ethological measure of the conflict between exploratory behavior
and retreat, was quantified in naive offspring, and in offspring exposed to
restraint stress (2 h). Restraint stress increased defensive withdrawal in both
control and prenatally stressed offspring. Both naive and restraint-stressed
prenatally stressed offspring exhibited increased defensive withdrawal compared
to control offspring. There was a significant interaction between prenatal stress
and restraint stress, suggesting increased vulnerability of prenatally stressed
offspring. The effects of restraint in the defensive withdrawal test were reduced
by intracerebroventricular administration of the CRF antagonists, alpha-helical
CRF9-41 (20 microg every hour) or D-phe(12), Nle(21, 38), C(alpha)-MeLeu(37)]
CRF((12-41)) (5 microg every hour) during the restraint period. The difference
between control and prenatally stressed offspring was abolished by the CRF
antagonists, suggesting that increased activation of CRF receptors may be a
factor in the behavioral abnormalities of prenatally stressed rats. Measurement
of CRF receptors in amygdala revealed a 2.5-fold increase in binding in
prenatally stressed offspring. In light of previous work from this laboratory
demonstrating increased content and release of CRF in amygdala from prenatally
stressed offspring, the present study suggests that the increased fearfulness of
prenatally stressed rats may be a consequence of increased activity of CRFergic
systems in the amygdala.
PMID- 11006436
TI - Role of IL-6 in cytokine-induced sickness behavior: a study with IL-6 deficient
mice.
AB - Interleukin-6 (IL-6) is synthesized and released in response to the cytokine
inducer lipopolysaccharide (LPS) and IL-1, and acts as an endogenous pyrogen.
Systemic administration of LPS and IL-1 to mice induces signs of sickness,
including reduction of social exploration, immobility and body weight loss. To
assess the role of IL-6 in the induction of sickness behavior, male IL-6
deficient mice (IL-6 -/-, Balb/cAn genetic background) were used and compared to
IL-6 +/+ littermates. The depressing effects of intraperitoneal LPS (2.5
microg/mouse) and IL-1beta (1.0 microg/mouse) on behavior and change in body
weight were more marked in IL-6 +/+ than in IL-6 -/- mice. The same difference
was observed when mice were injected with LPS (5 ng/mouse) and IL-1beta (1
ng/mouse) into the lateral ventricle of the brain (i.c.v.). These results show
that IL-6 released at the periphery and /or in the central nervous system plays a
role in the behavioral response to LPS and IL-1.
PMID- 11006437
TI - Diurnal rhythms of blood pressure, heart rate, and locomotor activity in adult
and old male Wistar rats.
AB - The diurnal rhythms of systolic blood pressure (SBP), diastolic BP (DBP), heart
rate (HR), and spontaneous locomotor activity (SLA) were determined in adult (6
month-old) and old (24-month-old) male Wistar rats by using radiotelemetry. The
rhythm parameters (mesor, amplitude, acrophase, and percent rhythm) were analyzed
by Fast-Fourier Transform and Cosinor methods. We found that the 12-h mean values
of SBP, DBP, HR, and SLA were significantly (p<0.001) higher in the dark phase
than in the light phase in both adult and old rats. The nocturnal 12-h mean value
of HR was significantly (p<0.01) lower in old than in adult rats. In addition,
the differences between diurnal and nocturnal 12-h mean values of SBP and HR were
reduced in old rats. There was no significant difference in the 12-h mean values
of SBP, DBP, and SLA between old and adult rats. Otherwise, the diurnal HR rhythm
amplitude was significantly (p<0.01) reduced in old rats (32+/-2 vs. 46+/-2 bpm).
A nearly 1-h delay in SBP and DBP acrophases (03h55 +/- 00h19 vs. 02h57 +/- 00h14
and 03h17 +/- 00h13 vs. 01h53 +/- 00h22, respectively) was found in old rats
comparing to adult rats. No significant change in SLA diurnal rhythm was observed
in old rats. In conclusion, these results show a decrease in the nocturnal 12-h
mean value of HR and an alteration in cardiovascular diurnal rhythms by a 1-h
delay of SBP and DBP acrophases and a reduction of HR rhythm amplitude in old
Wistar rats.
PMID- 11006438
TI - Parabrachial lesions disrupt responses of rats to amino acid devoid diets, to
protein-free diets, but not to high-protein diets.
AB - Normal rats "reduce" intake of diets that lack an essential amino acid (THR-DEV),
are protein free (PO%), or contain a high proportion of protein (P75%). We tested
the importance of the parabrachial nuclei (PBN) in signaling such adjustments of
food intake by placing electrophysiologically guided lesions in these nuclei at
points that responded to gustatory stimuli. When fed the THR-DEV diet, rats with
PBN lesions (PBNx) decreased their food intake significantly less than the
controls (78.5 vs. 44.4%). When put on a P0% diet, PBNx animals decreased their
intake only 8% compared with 23% for our CONT group. When put on a P75% diet,
however, both groups decreased their intake in an equivalent amount. These
experiments show that the PBN is involved in the learned aversion to an amino
acid devoid diet.
PMID- 11006439
TI - The way in which the data are combined affects the interpretation of short-term
feeding behavior.
AB - Short-term feeding behavior of pigs has been analyzed using random process models
and log-normal models. Both were successful despite very different underlying
assumptions relating to the theory of control. Feeder visits of growing pigs,
housed individually from 17 to 52 kg live weight, were recorded electronically
over a continuous period of 35 days. For the combined data, intervals between
visits to the feeder greater than 30 min could be described well by the negative
exponential model. The starting probability of a visit was constant at around
0.3, suggesting randomness. Disaggregating the data for individual pigs or for
individual weeks did not change this conclusion. Intervals in the day were of a
different nature to those at night, and disaggregation of the data into these two
periods revealed that the negative exponential model was not satisfactory for
either period. The starting probability for both periods increased with time
since the last visit. This is consistent with the idea of satiety. Therefore, the
apparent randomness in the data pooled across the day and night is an artefact
caused by pooling itself, and is not in conflict with the satiety concept. The
implications of data handling are discussed with reference to studies of the
physiological control of food intake.
PMID- 11006440
TI - Spontaneous meal patterns in female rats with and without access to running
wheels.
AB - Rats display strong behavioral rhythms during the ovarian cycle. During estrus,
food intake is minimal due to a decrease in meal size, and locomotor activity is
maximal. To investigate how activity influences feeding patterns across the
ovarian cycle, we used a computerized system to monitor spontaneous meal patterns
in intact, cycling female rats with and without access to running wheels. We
found that running wheel access decreased dark meal frequency, increased dark
meal size, and increased 24-h water intake during each phase of the ovarian
cycle. In contrast, body weight, 24-h food intake, and the ovarian rhythms of
reduced food intake, meal size, and body weight during estrus were not affected
by running wheel access. In particular, the reduction in food intake during
estrus was due to a selective reduction in dark meal size, not dark meal
frequency, and this occurred independent of wheel access. These data indicate
that estrus-related changes in spontaneous meal patterns and locomotor activity
are independently controlled and that the reduction in food intake during estrus
involves a selective change in the neurobiological controls of meal size.
PMID- 11006441
TI - Failure of neonatal clomipramine treatment to alter forced swim immobility:
chronic treadmill or activity-wheel running and imipramine.
AB - We examined whether chronic running on a treadmill or activity wheel would
attenuate the increased swim immobility that has been reported after neonatal
clomipramine (CLI) treatment. Male Sprague-Dawley pups (N = 60) were injected
with the monoamine reuptake inhibitor clomipramine hydrochloride (40 mg/kg per
day i.p.) from 8 to 21 days of age. Another group (N = 12) received saline
vehicle. At age 4 weeks, the CLI pups were randomly assigned to experimental
conditions: (1) sedentary; (2) 24-h access to an activity wheel; (3) sedentary
that received the antidepressant drug imipramine hydrochloride (10 mg/kg twice
daily) during the last 10 days of the experiment; (4) activity wheel +
imipramine; (5) treadmill running (30 m/min for 1 h at 0 degrees incline, 6
days/week). At age 16 weeks, rats underwent the Porsolt swim test 48 h after the
last imipramine injection and/or the last exercise session. The increase in swim
immobility among CLI-treated rats was small (one quarter of SD) and not
statistically significant (p>0.10). The results are not consistent with our
previous finding of antidepressant-like effects of activity-wheel running based
on brain noradrenergic adaptations and enhanced male copulatory performance after
neonatal CLI treatment. The lack of change in swim performance after clomipramine
questions the generalizability of the CLI model of depression and the validity of
the forced swim test as a behavioral measure of depression when it is used after
neonatal CLI injection or chronic activity-wheel running.
PMID- 11006442
TI - Release of hypothalamic norepinephrine during MSG intake in rats fed normal and
nonprotein diet.
AB - Effects of monosodium L-glutamate (MSG) solution (0.06 M) on interstitial levels
of norepinephrine (NE) were measured in the lateral hypothalamus (LH). Wistar
male rats, housed in standard operant boxes, were fed either normal or nonprotein
diet for 3 days. Beside a daily bar-mediated drinking session (75 min), animals
were without access to fluids. Microdialysates, collected from the LH during the
75 min of drinking, were analyzed using high-pressure liquid chromatography. No
significant responses of the LH NE to the drinking of distilled water, MSG, NaCl
(0.06 M), and glucose solution (0.6 M) were found in normally fed rats. However,
a specific decline in LH NE release was detected during MSG solution-drinking in
rats fed nonprotein diet. As MSG preference indicates protein intake, it is
possible that LH NE is, at least partially, one of the brain signals that relate
MSG preference to dietary protein intake.
PMID- 11006443
TI - Different pathways of neurohormonal hypothalamic control of the adrenal cortex
function in young and old rats.
AB - The pathways of hypothalamic control of the adrenal cortex function were studied
in the experiments on young and old male Wistar rats. Immunohistochemical,
morphometric, densitometric and radioimmunoassay methods were used. It was shown
that in young rats under stress vasopressin (VP) is released into the portal
circulation and probably in this way stimulates ACTH and enhances secretion of
corticosterone in the adrenal cortex. In old rats stress-reaction is delayed and
less adequate compared to young animals. It seems likely that in old rats VP is
secreted into the general circulation mainly via the posterior pituitary lobe
(PP), exerting a direct influence on the adrenal cortex. The conclusion is made
that in old rats regulation of the adrenal cortex function is realised via the
pathway phylogenetically more ancient than in young animals.
PMID- 11006444
TI - Changes with aging in the modulation of macrophages by norepinephrine.
AB - The effect of aging on the norepinephrine (NE)-induced modulation of phagocytic
and oxygen-dependent microbicidal processes of mouse peritoneal macrophages was
studied. Phagocytosis of latex beads on culture plates and superoxide anion
production was evaluated in young (12 weeks), adult (22 weeks), mature (48 weeks)
and old (72 weeks) BALB/c mice after in vitro incubation with 10(-12), 10(-9),
10(-7), 10(-5) or 10(-3) M concentrations of NE. The results indicate that the
phagocytic response to NE is quite similar in young and mature mice, with
increased phagocytosis after incubation with 10(-7) and 10(-3) M, and decreased
phagocytosis with 10(-5) M. Macrophages from adult mice increased their
phagocytic capacity after incubation with the highest concentrations of NE (10(
5) and 10(-3) M) and macrophages from old animals only were stimulated with 10(
3) M. In addition, it was found that usually NE increased the extracellular
superoxide anion production in the absence of phagocytosis in adult mice. No
statistically significant changes were found in intracellular superoxide anion
levels, but an increase was seen after phagocytosis in macrophages from adult,
mature and old animals, especially after incubation with 10(-5) M. In conclusion,
the results obtained indicate that the modulation of macrophages by NE does not
only depend on the concentration of this neurotransmitter, but also on age.
PMID- 11006445
TI - Sponge homologue to human and yeast gene encoding the longevity assurance
polypeptide: differential expression in telomerase-positive and telomerase
negative cells of Suberites domuncula.
AB - Porifera show a characteristic Bauplan in spite of the fact that (almost) all
cells are telomerase-positive and presumably provided with an unlimited potency
for cell proliferation. Studies revealed that telomerase-positive cells can be
triggered to telomerase-negative cells by dissociating them into single cells.
Single cells from the demosponge Suberites domuncula, in contrast to cells
present in primmorphs (a special form of cell aggregates), lack the property to
proliferate and they undergo apoptosis. One gene, SDLAGL, was identified in
primmorphs that showed high sequence similarity to the longevity assurance genes
from other Metazoa. In single cells no transcripts of SDLAGL could be identified,
while high expression was seen after re-aggregation of single cells and in
proliferating cells of primmorphs. We concluded that SDLAGL is involved in the
shift of telomerase-positive, proliferating cells to telomerase-negative, non
proliferating cells.
PMID- 11006446
TI - Age-related changes in interferon-alpha/beta receptor expression, binding, and
induction of apoptosis in natural killer cells from C57BL/6 mice.
AB - Natural killer (NK) cells are a critical first line of defense against viral
infections and tumors. We showed previously that basal NK cytotoxicity was
comparable in adult (6 month) and aged (24 month) C57BL/6 (B6) mice. However, NK
activity was significantly higher in adult compared with aged B6 mice after
either in vitro or in vivo stimulation with IFN-alpha/beta. The present study
explored whether age-related decreases in inducible NK activity after stimulation
with IFN-alpha/beta were due to differences in (1) IFN-alpha/beta receptor
expression or IFN-alpha/beta binding to NK cells or (2) apoptosis of NK cells.
Flow cytometry revealed that, despite significantly higher IFN-alpha/beta
receptor expression (P=0.03) on NK cells of aged mice, IFN-alpha/beta binding
to NK cells was comparable between adult and aged mice. In addition, IFN
alpha/beta treatment significantly increased Fas (CD95) expression (P=0.05) on
NK cells from both adult and aged mice. However, after IFN-alpha/beta
stimulation, NK cells from aged mice demonstrated significantly higher CD95
expression (P=0.03) and percent apoptosis (P=0.05) relative to adult mice.
These results suggest possible mechanisms for age-associated decreases in
inducible NK cytotoxicity after IFN-alpha/beta stimulation may include altered
IFN-alpha/beta receptors and/or increased percentages of NK cells undergoing
apoptosis.
PMID- 11006447
TI - Assessment of some important anatomical variations and dangerous areas of the
paranasal sinuses by computed tomography in children.
AB - The purpose of this study is to determine important variations and areas of risk
for major complications in paranasal computed tomography (CT). We also made
specific measurements for individual differences. This study consisted of 64
children (128 sides). Eleven participants had coronal and axial, and the
remaining 53 only coronal CT. The distance of the anterior ethmoidal artery (AEA)
and the lamina cribrosa to the inferior turbinate and the orbital roof, and the
depth of the lamina cribrosa were measured. The percentages of some of the
variations were as follows: upper attachment of uncinate process 25%, freely
coursing AEA 43%, aerated anterior clinoids 8%, optic canal bulging 6% and
extreme medially coursing carotid canal 3%. The frequencies of some of these
variations and the existence of Onodi cells were significantly smaller than
compared with adults. Specific measurements varied individually. In conclusion,
children deserve more attention while evaluating CT, due to their tiny bony
structures.
PMID- 11006449
TI - Parental values in the decision about cochlear implantation.
AB - Parents of children who are deaf are required to make decisions shortly after
diagnosis that will affect the child's method of communication and educational
placement. This study examines the role of parental values and preferences in
this decision making process. Twenty families with a deaf child participated in
this study. Parents from 19 of these families completed a multi-attribute
preference study, which assesses their preference for different outcomes in four
domains, i.e. academic achievement, social life, communication, and emotional
well being. In ten of these families, the child had received a cochlear implant.
Results indicate wide variability in parental preferences, which do not appear to
correlate with the parents' decisions to choose cochlear implantation. Interview
data from the study provides some insight into the parents' motivations. The
small size of the study limits further analysis of factors that influence
parents' choices and suggests further study with larger numbers of families.
PMID- 11006448
TI - Expression of inducible nitric oxide synthase (iNOS) in middle ear epithelial
cells by IL-1beta and TNF-alpha.
AB - OBJECTIVE: The importance of nitric oxide (NO) in the development of mucoid
middle ear effusion (MMEE) has been reported, but the mechanism regulating NO
release is unclear. We hypothesized that middle ear epithelial cells (MEEC) are
an important source of NO and that cytokines may be responsible for inducible
nitric oxide synthase (iNOS) mRNA expression in middle ear epithelial cells. This
study aims to identify and localize iNOS in middle ear epithelium, and to
characterize the effects of cytokines IL-1beta and TNF-alpha on the expression
and regulation of iNOS in rat middle ear epithelial cells. METHODS: In vitro
study: 40 Healthy adult Sprague-Dawley rats weighing 200-250 g were used as
donors of MEEC. Cultured MEEC were exposed to IL-1beta (10 ng/ml), TNF-alpha (5
ng/ml) or PBS (negative control) stimulation for 16 h. In vivo study: A total of
45 healthy adult Sprague-Dawley rats weighing 200-250 grams were used for this
study. The tympanic bullae were exposed bilaterally by a submandibular approach.
Animals were equally divided into three groups and inoculated with either 250 ng
of IL-1beta, 250 ng of TNF-alpha or PBS. A PBS group served as control.
Expression of iNOS mRNA in MEEC from both in vivo and in vitro studies was
determined by RT-PCR using specific primers. Expression of iNOS protein in MEEC
was determined by immunocytochemistry and Western blot using specific anti-iNOS
antibody. RESULTS: Primary culture of rat MEEC was positively stained by
cytokeratin antibody, but not by vimentin, indicating the epithelial origin of
the cultured cells. RT-PCR revealed that cultured MEEC without treatment of IL-1
beta or TNF-alpha did not express iNOS mRNA whereas cultured MEEC treated with IL
1beta or TNF-alpha for 16 h expressed iNOS mRNA. Both immunocytochemistry and
Western blot demonstrated the expression of iNOS protein in the majority of
cultured MEEC treated with IL-1beta or TNF-alpha for 16 h, whereas the expression
of iNOS protein was not detectable in MEEC without treatment. Expression of iNOS
protein in vivo was observed in middle ear mucosa treated with IL-1beta and TNF
alpha by immunohistochemistry. CONCLUSION: Expression of iNOS mRNA and iNOS
protein is induced in MEEC following the treatment of cytokines IL-1beta or TNF
alpha both in vivo and in vitro. The results of the present study demonstrate
that rat MEEC possess the capacity to express iNOS after IL-1beta and TNF-alpha
stimulation.
PMID- 11006450
TI - Efficacy of ceftibuten in 5 versus 10 days treatment of recurrent acute otitis
media in children.
AB - OBJECTIVE: in recurrent acute otitis media (AOM) several alternative treatments
are suggested, e.g. cephalosporins. Information about the optimal duration of
treatment in recurrent AOM is sparse. The aim of the present study was to compare
the efficacy of ceftibuten in 5 versus 10 days treatment in recurrent AOM in
children. METHODS: this was a single-blind (doctor blinded), randomized,
multicentre study with two parallel groups. Eleven investigators at six centres
in the west of Sweden enrolled a total of 180 patients. Outpatients with a new
clinical AOM within 1 month were randomized to 5 or 10 days treatment with
ceftibuten, 9 mg/kg/day, as a single dose. RESULTS: the mean age of the patients
was 1.2 years (range 6 months-8 years). The patients had on average had three
antibiotic treatments during the preceding 12 months. The recurrence rates in the
5- and 10-day groups were 21.4 and 4.5%, respectively, at first follow-up visit
day 12 (P=0.001). The total recurrence rates between the two groups during the
whole follow-up period of 40 days, 35 and 30%, respectively, did not differ
significantly. The rate of recurrence did not correlate to nasopharyngeal
findings of Streptococcus pneumoniae or Haemophilus influenzae. Pneumococci with
decreased susceptibility to penicillin were found in 5% of all pneumococci, and
beta-lactamase producing H. influenzae in 8%. Adverse events were reported less
frequently in the 5- compared with the 10-day treatment group. CONCLUSION: this
study on young children with recurrent otitis media has shown no statistical
difference between ceftibuten given once daily for 5 and 10 days as determined on
day 40. The 10-day treatment was significantly better at early follow-up.
PMID- 11006451
TI - Congenital cysts and fistulas of the neck.
AB - This retrospective study describes a series of 191 children treated for
congenital cysts and fistulas of the neck between 1984 and 1999 in the pediatric
ORL Department of La Timone Children's Hospital. Preauricular fistulas and cystic
hygromas were not included. The anomalies in this series were classified as
either malformations of the midline or malformations of laterocervical region.
Malformations of the midline included the thyroglossal duct cysts (n=102) and
dermoid cysts (n=21). The most common malformations of the laterocervical region
were cysts and fistulas of the second cleft (n=37) followed by those of the first
cleft (n=20),those of the fourth pouch (n=7), and thymic cysts (n=4). Diagnosis
of malformations of the midline is usually straightforward. However, diagnosis of
malformation of the laterocervical region can be problematic. Misdiagnosis often
leads to inadequate treatment with recurrence and functional as well as cosmetic
sequelae.
PMID- 11006452
TI - Etiology of deafness in Afyon school for the deaf in Turkey.
AB - OBJECTIVE: Otolaryngologists play an important role in the evaluation of children
with a hearing impairment. The group of unknown cause still has a high incidence.
The purposes of this study were to determine the etiology of deafness in Afyon
School for the Deaf in Turkey and to compare the results with the other studies
from Turkey and other countries. METHODS: This study was a retrospective analysis
of 130 deaf students, aged 5-16 years. Medical and family histories of the
children were obtained. Clinical and laboratory examinations were carried out.
RESULTS: Etiological groups showed the following distribution: febril convulsion,
26.9%; cause unknown, 26.1%; hereditary group, 23.8%; meningitis, 10%; measles,
6.1%; and miscellaneous, 6.6%. A total of 90.3% of the students with hereditary
deafness were from consanguineous families. A marital consanguinity was noted in
the parents of 64 (49.2%) of all children in the school and this rate was higher
than the average in Turkey (P<0.05). Neither syndromic deafness nor maternal
rubella was identified. A total of 27.6% of the cases were diagnosed after the
age of 30 months. CONCLUSION: Febril convulsions and hereditary factors were the
major causes of hearing loss in the present study. The high incidence of
consanguineous marriage among the parents of the children with hereditary
deafness seemed a strong evidence of genetic origin, indicating a close
relationship between them. Congenital rubella syndrome did not appear as a
significant etiology of deafness in Turkey.
PMID- 11006453
TI - Changes in the aetiology of hearing impairment in deaf-blind pupils and deaf
infant pupils at an institute for the deaf.
AB - An aetiological study was performed on 57 pupils at the deaf-blind department of
the Institute for the Deaf at Sint-Michielsgestel, The Netherlands, in the school
year 1998-1999 and on 49 deaf-blind pupils at the same department in the school
year 1986-1987. The pupils were 5-20 years of age. In addition, the aetiologies
were studied in 55 deaf infant pupils in 1998 and compared with those of 68 deaf
infant pupils in 1988. Their age was 1-5 years. All the pupils showed hearing
impairment with thresholds of >60 dB HL. Among the deaf-blind pupils and deaf
infant pupils, there were several cases with rare hereditary syndromes. The
prevalence of acquired causes of deafness, especially congenital rubella, had
decreased over the years, whereas perinatal causes of deafness had increased.
Chromosomal anomalies were found in 15% of the infant pupils in 1998. Over the
study period, the percentage of pupils with multiple handicaps increased from 25
to 38%.
PMID- 11006454
TI - Bilateral ethmoidal mucocele in cystic fibrosis: report of a case.
AB - The purpose of this study is to report a rare and interesting case of a 10-month
old boy who presented a bilateral ethmoidal mucocele associated with cystic
fibrosis and to discuss, according to the literature, the sinonasal involvement
in this disease. Only nine pediatric patients with both disorders have been
reported previously in literature, and all of these cases were older than 1 year
4 months and presented with a unilateral mucocele.
PMID- 11006455
TI - Nasopharyngeal carcinoma in children.
AB - Nasopharyngeal carcinoma (NPC) is rare in children. We report two cases from KK
Women and Children's Hospital in Singapore, who presented with advanced
locoregional disease. The various aspects of NPC in children are discussed. It is
more common in males and black adolescents. The etiology is probably different
from that in adult. Undifferentiated NPC or lymphoepithelioma is the commonest
variety. Confusing symptoms like cervical lymphadenopathy and unilateral otitis
media with effusion (OME) are among the commonest presentations. When children
present with both conditions simultaneously, it is imperative to manage them like
adult patients and perform nasendoscopy to rule out NPC. The disease stage at
presentation is often more advanced compared with adults. These tumors are,
however, associated with a higher cure rate as they are most radiosensitive.
Radiotherapy with neo-adjuvant chemotherapy is currently the treatment of choice.
Both cases achieved satisfactory control of the disease and are presently under
close follow-up.
PMID- 11006456
TI - Prefabrication provides synapses on demand.
PMID- 11006457
TI - Does the head rule the heart?
PMID- 11006458
TI - Genotype x environment interaction: an old problem in a new field.
PMID- 11006459
TI - Adult versus embryonic stem cells: which is the way forward?
PMID- 11006460
TI - Behavioral neuroscience: challenges for the era of molecular biology.
AB - This is a great age to participate in biological inquiry. Behavioral neuroscience
offers a rich perspective for molecular biologists. However, behavioral analysis
is not simply an assay. Whereas molecular biology has become a unique tool in the
armamentarium of behavioral neuroscience, the powerful methodology of molecular
biology is no substitute for careful behavioral exploration.
PMID- 11006461
TI - Cell death in early neural development: beyond the neurotrophic theory.
AB - The important effect of cell death on projecting neurons during development is
well established. However, this mainstream research might have diverted
recognition of the cell death that occurs at earlier stages of neural
development, affecting proliferating neural precursor cells and young
neuroblasts. In this article, we briefly present observations supporting the
occurrence of programmed cell death during early neural development in a
regulated fashion that to some extent parallels the death of projecting neurons
lacking neurotrophic support. These findings raise new questions, in particular
the magnitude and the role of this early neural cell death.
PMID- 11006462
TI - Control of dorsal raphe 5-HT function by multiple 5-HT(1) autoreceptors: parallel
purposes or pointless plurality?
AB - The serotonergic cells of the dorsal raphe nucleus innervate much of the
forebrain and are thought to be involved in the mechanism of action of
antidepressants. Dysfunction of these cells might be involved in the neural
mechanisms underlying depression and suicide. The traffic in pathways emanating
from the dorsal raphe nucleus is controlled by 5-HT(1) autoreceptors. Until
recently it was thought that the autoreceptors in the dorsal raphe nucleus were
solely of the 5-HT(1A) subtype. In this article, we discuss evidence that the
situation is more complex and that multiple 5-HT(1) subtypes govern different
aspects of 5-HT function in the dorsal raphe nucleus presenting new therapeutic
opportunities.
PMID- 11006463
TI - G-protein-independent signaling by G-protein-coupled receptors.
AB - Two classes of receptors transduce neurotransmitter signals: ionotropic receptors
and heptahelical metabotropic receptors. Whereas the ionotropic receptors are
structurally associated with a membrane channel, a mediating mechanism is
necessary to functionally link metabotropic receptors with their respective
effectors. According to the accepted paradigm, the first step in the metabotropic
transduction process requires the activation of heterotrimeric G-proteins. An
increasing number of observations, however, point to a novel mechanism through
which neurotransmitters can initiate biochemical signals and modulate neuronal
excitability. According to this mechanism metabotropic receptors induce responses
by activating transduction systems that do not involve G-proteins.
PMID- 11006464
TI - Common regions of the human frontal lobe recruited by diverse cognitive demands.
AB - Though many neuroscientific methods have been brought to bear in the search for
functional specializations within prefrontal cortex, little consensus has
emerged. To assess the contribution of functional neuroimaging, this article
reviews patterns of frontal-lobe activation associated with a broad range of
different cognitive demands, including aspects of perception, response selection,
executive control, working memory, episodic memory and problem solving. The
results show a striking regularity: for many demands, there is a similar
recruitment of mid-dorsolateral, mid-ventrolateral and dorsal anterior cingulate
cortex. Much of the remainder of frontal cortex, including most of the medial and
orbital surfaces, is largely insensitive to these demands. Undoubtedly, these
results provide strong evidence for regional specialization of function within
prefrontal cortex. This specialization, however, takes an unexpected form: a
specific frontal-lobe network that is consistently recruited for solution of
diverse cognitive problems.
PMID- 11006465
TI - Live or let die - retinal ganglion cell death and survival during development and
in the lesioned adult CNS.
AB - Programmed cell death or apoptosis is a common and widespread phenomenon that is
important for proper development of the nervous system. In the adult CNS,
however, apoptosis contributes to secondary cell loss after various types of
lesions. The retino-tectal system has been successfully used as a convenient
model system to study the molecular mechanisms of neuronal apoptosis and survival
during development and in the lesioned adult CNS. This review describes the
current knowledge about the interactions of cell death and survival pathways in
general and for retinal ganglion cells specifically.
PMID- 11006467
TI - Context, state and the receptive fields of striatal cortex cells.
AB - Visual cortical cells are commonly characterized by their receptive-field
structure. Originally, a visual receptive field was defined in a purely spatial
way as that retinal area from which a change in spiking response of the regarded
cell could be elicited by visual stimulation. The first attempts to understand
receptive-field structure were based entirely on the anatomical connectivity of
the primary visual pathway. More recently, however, it has been discovered that
the spatial and temporal context in which a stimulus is presented to a cell can
strongly influence its receptive field, and this in turn is dependent on the
state of arousal and attention. Accordingly, new concepts recognize that cortical
receptive fields are highly dynamic entities embracing more than the sum of the
full spatial and temporal response properties of a cell.
PMID- 11006466
TI - New perspectives on enigmatic vanilloid receptors.
AB - In spite of the rapid advances in our understanding of vanilloid-receptor
pharmacology in the PNS, the function of vanilloid receptors in the brain has
remained elusive. Recently, the endocannabinoid anandamide has been proposed to
function as an endogenous agonist at the vanilloid receptor VR1. This is an
exciting hypothesis because the localization of VR1 overlaps with that of
anandamide and its preferred cannabinoid receptor CB(1) in various brain areas.
The interaction of anandamide and/or related lipid metabolites with these two
completely separate receptor systems in the brain clearly places VR1 in a much
broader role than pain perception. At a practical level, the overlapping ligand
recognition properties of VR1 and CB(1) might be exploited by medicinal
chemistry. For example, arvanil, a 'chimeric' ligand that combines structural
features of capsaicin and anandamide, promises to be an interesting lead for new
drugs that interact at both vanilloid and cannabinoid receptors.
PMID- 11006469
TI - The plasmodium vivax and P. berghei gene sequence tag projects
PMID- 11006468
TI - Molecular approaches to malaria: seeking the whole picture.
AB - This year, Australia hosted its first major international conference on malaria -
Molecular Approaches to Malaria in Lorne, Victoria, 2-5 February 2000 (MAM2000).
The worldwide research effort toward a better understanding of the pathogenesis
and control of malaria in the post-genomic era was discussed and debated by over
250 researchers from 18 countries during four days packed with molecular biology,
cell biology, genomics, vaccines and pathogenic mechanisms. This special malaria
edition of Parasitology Today is an attempt to capture and summarize the quality
and breadth of work presented at the conference and place this in the context of
the current global malaria research effort; eight of the nine Reviews in this
issue have been written by session chairs or presenters at MAM2000.
PMID- 11006470
TI - Rupture and drug combinations on the Web
PMID- 11006471
TI - Host cell invasion by malaria parasites.
AB - The complex life cycle of the malaria parasite includes three specialized
invasive stages, distinct both in terms of their cellular architecture and in
their choice of target host cell. Despite the dissimilarities between these
forms, there are clear parallels in the manner by which they enter their
respective host cells. Advances in the area of erythrocyte invasion by the
malaria merozoite, outlined here by Chetan Chitnis and Mike Blackman and
discussed at the Molecular Approaches to Malaria conference, Lorne, Australia, 2
5 February 2000, will undoubtedly impact on our understanding of mechanisms of
cell entry by the other invasive forms. Similarly, recent progress in dissecting
the functional role of surface proteins expressed by sporozoite and ookinete
stages has provided fascinating insights into general aspects of invasion by all
invasive stages of apicomplexan parasites.
PMID- 11006472
TI - Falciparum malaria: sticking up, standing out and out-standing.
AB - Cytoadherence is believed to be fundamental for the survival of Plasmodium
falciparum in vivo and, uniquely, is a major determinant of the virulence of this
parasite. Despite the widely professed importance of cytoadhesion in the
development of severe disease, there are a number of aspects of this highly
complex process that remain poorly understood. Recent progress in the
understanding of cytoadhesive phenomena was discussed extensively at the
Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000.
Here, Brian Cooke, Mats Wahlgren and Ross Coppel consider just how far we have
progressed during the past 30 years and highlight what is still missing in our
understanding of the mechanisms and clinical relevance of this apparently vital
process.
PMID- 11006473
TI - Traffic jams: protein transport in Plasmodium falciparum.
AB - Protein targeting in malaria parasites is a complex process, involving several
cellular compartments that distinguish these cells from more familiar systems,
such as yeast or mammals. At least a dozen distinct protein destinations are
known. The best studied of these is the vestigial chloroplast (the apicoplast),
but new tools promise rapid progress in understanding how Plasmodium falciparum
and related apicomplexan parasites traffic proteins to their invasion-related
organelles, and how they modify the host by trafficking proteins into its
cytoplasm and plasma membrane. Here, Giel van Dooren and colleagues discuss
recent insights into protein targeting via the secretory pathway in this
fascinating and important system. This topic emerged as a major theme at the
Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000.
PMID- 11006474
TI - A brief illustrated guide to the ultrastructure of Plasmodium falciparum asexual
blood stages.
AB - Interpretation of the new information arising from the Plasmodium falciparum
Genome Project requires a good working knowledge of the ultrastructure of the
parasite; however many aspects of the morphology of this species remain obscure.
Lawrence Bannister, John Hopkins and colleagues here give an illustrated overview
of the three-dimensional (3-D) organization of the merozoite, ring, trophozoite
and schizont stages of the parasite, based on available data that include 3-D
reconstruc-tion from serial electron microscope sections. The review describes
the chief organelles present in these stages, emphasizing the continuity of
structure in addition to specialized, stage-specific features developed during
the asexual erythrocytic cycle.
PMID- 11006475
TI - Malaria research in the post-genomic era.
AB - Within the next few years, the complete genomic sequences of Plasmodium
falciparum, and potentially several other Plasmodium spp, will be available to
researchers worldwide. These complete genomic sequence data are certain to
provide the foundation for nearly all malaria research in the next decades, as
discussed here by Dan Carucci.
PMID- 11006476
TI - Antimalarial drug development and new targets.
AB - The Molecular Approaches to Malaria (MAM2000) conference, Lorne, Australia, 2-5
February 2000, brought together world-class malaria research scientists. The
development of new tools and technologies - transfection, DNA microarrays and
proteomic analysis - and the availability of DNA sequences generated by the
Malaria Genome Project, along with more classic approaches, have facilitated the
identification of novel drug targets, the development of new antimalarials and
the generation of a deeper understanding of the molecular mechanism(s) of drug
resistance in malaria. It is hoped that combinations of these technologies could
lead to strategies that enable the development of effective, efficient and
affordable new drugs to overcome drug-resistant malaria, as discussed at MAM2000
and outlined here by Ian Macreadie and colleagues.
PMID- 11006477
TI - Malaria vaccines.
AB - Although the possibility of a live attenuated malaria vaccine has been
considered, current malaria vaccine development activities are dominated by
attempts to develop a subunit vaccine. Hence, it is entirely appropriate that a
session of the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5
February 2000, was devoted to vaccine development. The oral presentations in this
session and the relevant poster presentations are outlined here by Robin Anders
and Allan Saul.
PMID- 11006478
TI - Molecular approaches to epidemiology and clinical aspects of malaria.
AB - Malaria is a problem of global importance, responsible for 1-2 million deaths per
year, mainly in African children, as well as considerable morbidity manifested as
severe anaemia and encephalopathy in young children. Fundamental to the
development of new tools for malaria control in humans is an increased
understanding of key features of malaria infection, such as the diversity of
outcome in different individuals, the understanding of different manifestations
of the disease and of the mechanisms of immunity that allow clinical protection
in the face of ongoing low-grade infection (concomitant immunity or premunition).
Here, Graham Brown and colleagues review some of the ways in which molecular
approaches might be used to increase our understanding of the epidemiology and
clinical manifestations of malaria, as discussed at the Molecular Approaches to
Malaria conference (MAM2000), Lorne, Australia, 2-5 February 2000.
PMID- 11006479
TI - Pathogenesis of malaria.
AB - As the mortality rate of 20-30% for severe falciparum malaria under even the best
clinical conditions testifies, access to antimalarial drugs is not sufficient to
prevent an appreciable mortality from this disease. Understanding the cause of
death at a cellular level is essential if additional rational treatments are to
be developed. Here, Ian Clark and Louis Schofield discuss recent work presented
at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February
2000, that updates the cytokine-based concept of malarial disease.
PMID- 11006480
TI - Application of (quantitative) structure-activity relationships to progestagens:
from serendipity to structure-based design.
AB - Progestagens are drugs, which are widely used in hormonal contraception and in
hormone-replacement therapy. Since the natural hormone, progesterone, lacks oral
activity, much effort has been devoted to finding analogues with improved oral
activity and, preferably, higher potency and selectivity. A crystal structure of
the hormone binding domain (HBD) region of the progesterone receptor (PR) could
only be obtained recently. For more than forty years the process of designing new
progestagens could therefore only be guided by the knowledge of the structure of
the ligand and its corresponding in vitro/in vivo activities. While in early days
chemical intuition and simple statistics (structure-activity relationship - SAR)
were leading the drug design process, in later days more complex statistics and
visualization tools have become routinely part of quantitative structure-activity
relationship (QSAR) studies. The present review aims to provide a general
overview of the strategies, efforts and achievements of synthetic and
computational chemists in more than forty years of development of progestagens.
PMID- 11006481
TI - Synthesis of ionones and carvone analogues: olfactory properties and preliminary
toxicity assays.
AB - Vilsmeier reagents react with alpha/beta-ionones and carvone to produce aldehydes
7-11 in a one-step procedure. The indene derivative 11, which came from the
double iminoalkylation of carvone and ring closure with the elimination of
dimethylamine, was practically odourless, while all the others had peculiar
odours which were very different from the starting material. The cytotoxicity
data of 9 and 10, which are the most promising potential perfume ingredients, are
also reported.
PMID- 11006482
TI - Synthesis and cytotoxicity of gossypol related compounds.
AB - Gossypol, gossypolone, reduced gossypol and new Schiff's bases of racemic
gossypol and gossypolone were extracted or synthesized. Their cytotoxic
activities on KB human cancer cells were determined. Gossypolone and the
ethylamine derivative of gossypolone were the most active compounds (IC(50) in
the micromolar range in both cases). The cytotoxicity of gossypol and gossypolone
was increased when the tests were performed in the absence of serum and decreased
when catalase as well as mannitol were added to the culture medium.
PMID- 11006483
TI - Synthesis and beta-blocking activity of (R,S)-(E)-oximeethers of 2, 3-dihydro-1,8
naphthyridine and 2,3-dihydrothiopyrano[2, 3-b]pyridine:potential
antihypertensive agents - part IX.
AB - The synthesis of oximeethers of 2,3-dihydro-1,8-naphthyridine and 2, 3
dihydrothiopyrano[2,3-b]pyridine is described. These compounds exhibit a
selective beta-blocking activity, with a selectivity towards beta(2)-receptors.
Groups in the N(1) position giving rise to a considerable steric hindrance led to
a higher beta(2)-blocking selectivity, whereas groups creating a moderate
hindrance caused a weak but significant decrease in beta(2)-antagonist potency.
Substitution of the N(1)-R group with a sulfur atom led to compounds possessing
beta(1)-, beta(2)- and beta(3)-blocking properties. Compounds 9c(1) and 10a(1)
showed a beta(3)-antagonist activity slightly lower than that of propranolol.
PMID- 11006484
TI - Synthesis and antiproliferative activity of some variously substituted acridine
and azacridine derivatives.
AB - A group of 9-substituted acridine and azacridine derivatives (m-AMSA analogues)
were synthesised following classical procedures as potential antitumour agents
with inhibitory effects on DNA topoisomerase II. Some were found to have
noticeable cytotoxicity against human HL-60 and HeLa cells grown in culture.
Their non-covalent interactions with calf thymus DNA have been studied using
fluorescence quenching. We evaluated DNA damage produced by the tested compounds
by means of DNA filter elution and protein precipitation techniques. Catalytic
studies carried out with purified topoisomerase confirmed these agents as
antitopoisomerase inhibitors. Chemotherapy of solid-tumour-bearing mice with
tested compounds allowed an aza-analogue (compound IIIb), as potent as m-AMSA but
less toxic towards the host, to be recognised.
PMID- 11006485
TI - Synthesis of (1S,3aS)-8-(2,3,3a,4,5, 6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8
triaza-spiro[4. 5]decan-4-one, a potent and selective orphanin FQ (OFQ) receptor
agonist with anxiolytic-like properties.
AB - The development of 8-(2,3,3a,4,5, 6-hexahydro-1H-phenalen1-yl)-1-phenyl-1,3,8
triaza-spiro[4. 5]decan-4-ones 3 starting from (RS)-8-acenaphten-1-yl-1-phenyl
1,3, 8-triazaspiro[4.5]decan-4-one 1 is reported. The synthesis and the binding
affinities at human OFQ and opioid (micro, kappa, delta) receptors of the
stereoisomers 3a-f are described. In vitro the most selective compound, (1S,3aS)
8-(2,3,3a,4,5, 6-hexahydro-1H-phenalen1-yl)-1-phenyl-1,3,8-triaza-spiro[4.
5]decan-4-one 3c, was found to act as a full agonist at the OFQ receptor in the
GTPgamma(35)S binding test. It turned out to be selective versus a variety of
other neurotransmitter systems. When tested in vivo following intraperitoneal
injection, compound 3c was found to decrease neophobia in a novel environment and
to exhibit dose-dependent anxiolytic-like effects in the elevated plus-maze
procedure, thus confirming the effects observed following intracerebroventricular
infusion of the OFQ peptide in rat.
PMID- 11006486
TI - Synthesis and antibacterial activity of some 5-guanylhydrazone/thiocyanato-6
arylimidazo[2,1-b]-1,3, 4-thiadiazole-2-sulfonamide derivatives.
AB - 6-Arylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamides 3 on Vilsmeier-Haak
reaction produced 5-formyl-6-arylimidazo[2,1-b]-1,3, 4-thiadiazole-2-[N
(dimethylaminomethino)]sulfonamides 4, while 3 on treatment with potassium
thiocyanate in the presence of bromine in acetic acid produced 5-thiocyanato-2
sulfonamides 6. Interaction of 4 with aminoguanidine hydrochloride in ethanol
produced the corresponding 5-guanylhydrazone derivatives 5. Compounds 5 and 6
showed a high degree of antibacterial activity against both Escherichia coli and
Staphylococcus aureus comparable to that of sulfamethoxazole and Norfloxacin.
However, they were found to show moderate activity against Salmonella typhi,
Pseudomonas aeruginosa and Pneumococci.
PMID- 11006487
TI - Carbonic anhydrase inhibitors. Part 86. A QSAR study on some sulfonamide drugs
which lower intra-ocular pressure, using the ACE non-linear statistical method.
AB - Quantum chemical QSAR expressions have been developed for a heterogeneous group
of 36 sulfonamides which have been shown to lower intraocular pressure in in vivo
tests on animals. It was found, using the ACE statistical technique, that the
lowering of intraocular pressure correlated non-linearly with K(I) for carbonic
anhydrase inhibition and with solubility. Non-linear transformations had to be
applied to both the response variable and to solubility. Chemical variables found
to be relevant to CA inhibition included the dipole moment vector, the frontier
orbital energies, the solvation energy determined by the COSMO model, the
electrostatic potential based charges on the atoms of the sulfonamide group, and
the size and polarizability of the molecule.
PMID- 11006488
TI - Diagnostic imaging facilities for the general practitioner.
PMID- 11006489
TI - Survey of the management of deep vein thrombosis in general practice in the
Netherlands.
AB - BACKGROUND: To investigate the management of (suspected) deep vein thrombosis in
general practice. METHODS: Self completing postal questionnaire among a random
sample of 692 general practitioners in the Netherlands. RESULTS: The overall
response rate was 58%. Eighty-nine percent of the respondents initiated objective
evaluation. Less than 3% usually make the diagnosis on clinical grounds only.
Ninety-two percent initiated adequate treatment for the last patient with deep
vein thrombosis. No more than 4% usually treat patients with acenocoumarol alone.
Respondents frequently referred a patient to a specialist, 41% to confirm the
diagnosis and 85% for treatment. Already 44% feel that management of deep vein
thrombosis is a mandate of the general practitioner. For those who do not, the
availability of diagnostic and therapeutic facilities are the main obstacles.
CONCLUSION: In general practice objective diagnostic methods to evaluate
suspected deep vein thrombosis are routinely used and patients receive adequate
treatment. Although patients are frequently referred to the hospital many general
practitioners feel that they should be able to take care of these patients
themselves. (See Editorial p. 133)
PMID- 11006490
TI - Availability of diagnostic facilities in the Netherlands for patients with
suspected pulmonary embolism. ANTELOPE Study Group. Advances in New Technologies
Evaluating the Localisation of Pulmonary Embolism.
AB - Pulmonary embolism remains a complex diagnostic problem. Although accurate and
cost-effective, the 'Dutch consensus' strategy is not widely applied. We assessed
the availability and investment plans of the different facilities used in this
strategy. Furthermore, the current and future availability of new diagnostic
modalities was investigated. A questionnaire was sent to all Dutch hospitals. The
questionnaire contained separate sections with questions for the hospital
management and the medical practitioners at the departments of radiology, nuclear
medicine, internal medicine and pulmonology. Five hundred and eighty-four
questionnaires were sent out (response rate 68%). Forty-three percent of the
hospitals had no nuclear medicine facility, 11% had no pulmonary angiography
facility, and 59% had no spiral CT scan (SCTA). Forty-six percent of the
responding hospitals had a nuclear medicine facility; and 5% used Technegas for
ventilation studies. Strategies with SCTA were available in about 27% of the
hospitals. Due to future investments this number will increase to approximately
55%. Strategies with Technegas were available in 2.4% of the hospitals, this
number might increase to 25% if Technegas is proven accurate. The 'Dutch
consensus' strategy is available in two-thirds of the hospitals. All other
strategies were less feasible. Several equivalent strategies for diagnosing
pulmonary embolism should be developed. These strategies should be accurate,
widely available and accepted.
PMID- 11006491
TI - Positron emission tomography for the detection of metastases of differentiated
thyroid carcinoma.
AB - OBJECTIVE: To show the value of positron emission tomography (PET) with 18-F
fluorodeoxyglucose (18-FDG) for the detection of metastases of differentiated
thyroid carcinoma in selected patients. PATIENT HISTORIES: There were four
patients, who had undergone total thyroidectomy for papillary (two) or follicular
thyroid carcinoma (two). All patients had subsequent treatment with (131)iodine.
Three patients had an increasing serum concentration of thyroglobulin, one
patient had antibodies against thyroglobulin. A diagnostic (131)iodine
scintigraphy was negative in two patients, and uncertain in two patients.
Positron emission tomography was performed about 45 min after administration of
10 mCi 18-F-fluorodeoxyglucose. In three patients PET showed uptake in the
cervical region, caused by lymph node metastases in two (confirmed by neck
dissection) and recurrent tumor on the trachea in one patient (confirmed by
surgery). In the fourth patient uptake of 18-FDG was seen in the neck and in both
lungs. This led to discontinuation of treatment with (131)iodine because the lung
metastases did not accumulate (131)iodine. DISCUSSION: In selected patients with
differentiated thyroid carcinoma with an increasing serum concentration of
thyroglobulin, PET is an important diagnostic option when scintigraphy with
(131)iodine is negative or uncertain. In the four presented case histories, the
results of PET led to a therapeutic decision: surgery in three patients and
discontinuation of (131)iodine in one patient. The development of guidelines for
the use of PET in the diagnosis of recurrent thyroid cancer is discussed.
PMID- 11006492
TI - Normal perfusion scintigraphy in pulmonary embolism. Causes and diagnostic
alternatives.
AB - Diagnosing pulmonary embolism (PE) is a challenge for many physicians as it is a
frequently occurring disease with nonspecific symptoms and signs. Ventilation
perfusion (V/Q) scintigraphy is widely used as the first step in diagnosing PE
since it is non-invasive and highly sensitive. With a normal perfusion scan,
clinically relevant pulmonary thrombo-emboli are considered to be absent. In an
ongoing study assessing the value of spiral CT in the diagnosis of PE, we
encountered a patient who had a normal perfusion scan while a large partially
occluding thrombus in the right lower lobe artery and its branches was depicted
by spiral CT and pulmonary angiography. In this article, we discuss the
significance of normal findings in perfusion scintigraphy, the causes of false
negative perfusion scans and the role of alternative techniques such as spiral CT
and pulmonary angiography.
PMID- 11006493
TI - An Epstein-Barr virus-associated pulmonary lymphoproliferative disorder as
complication of immunosuppression.
AB - Inherited or acquired immunodeficiencies as well as autoimmune diseases treated
with cytotoxic drugs are associated with an increased incidence of lymphoma. Non
Hodgkin's lymphomas that occur in the context of drug-induced immunosuppression,
acquired or congenital immunodeficiency, are frequently associated with Epstein
Barr virus infection. This report describes the occurrence of an Epstein-Barr
virus associated pulmonary B cell lymphoma in a patient with longstanding
rheumatoid arthritis treated with methotrexate.
PMID- 11006494
TI - Disseminated intravascular coagulation as an unusual presentation of an Epstein
Barr virus infection.
AB - Epstein-Barr viral (EBV)-infection usually presents as fever, sore throat,
fatigue, lymphadenopathy and atypical lymphocytosis. We describe a patient with
disseminated intravascular coagulation as the presenting symptom caused by a
primary EBV infection.
PMID- 11006495
TI - The (non-)sense of the methionine loading test for detecting
hyperhomocysteinaemia.
PMID- 11006496
TI - Oestrogens and lower urinary tract function.
AB - There is increasing evidence from animal and human studies that sex steroids have
an important effect on the female lower urinary tract during adult life.
Oestrogen receptors have been identified throughout the brain, pontine
micturition centre and in the bladder, urethra and pelvic floor. Fluctuations in
the circulating level of oestrogens and progesterone occurring during the
menstrual cycle and in pregnancy influence the prevalence of urinary symptoms and
the results of urodynamic investigation. In addition, the menopause and
subsequent oestrogen deficiency have been implicated in the aetiology of a number
of urogenital complaints including incontinence, urgency and recurrent urinary
tract infection (UTI). However, the use of hormone replacement therapy for these
conditions has given conflicting and largely disappointing results. The aim of
this paper is to discuss the role of oestrogen in the pathogenesis and treatment
of lower urinary tract dysfunction.
PMID- 11006497
TI - Self-defined menopausal status in a multi-ethnic sample of midlife women.
AB - OBJECTIVES: This study aimed to identify factors associated with women's
perceived menopausal status and to evaluate agreement between women's self
designation and a menstrually-based classification in a multi-ethnic sample of
women. METHODS: A cross-sectional survey was conducted as part of a large, seven
site, multi-ethnic study, the Study of Women's Health Across the Nation (SWAN).
All variables were assessed by self-report in 13952 women aged 40-55 years.
Multiple linear regression was used to assess determinants of self-defined
menopausal status, stratifying by race/ethnicity within three anatomical/hormone
use strata. Kappa statistics were used to evaluate agreement between the self
defined and menstrually-based classifications. RESULTS: For women with an intact
uterus, at least one ovary and not using hormones, menstrual patterns explained
about half the variance in self-defined menopause status with older women
classifying themselves later in the transition. Disagreement between menstrually
based and self-defined menopausal status was 39, 38, 36, 32 and 29% for Hispanic,
African-American, Japanese, Caucasian, and Chinese women, respectively (kappa
statistics=0.46, 0.41, 0.40, 0.53 and 0.58). Women with vasomotor symptoms tended
to self-designate themselves as being in transition regardless of their menstrual
patterns. Age and 12 months of amenorrhea explained about 40% of the variance in
self-categorization among women using hormones with an intact uterus. Bilateral
oophorectomy, age and time since surgery explained about 20% of the variance
among post-surgical women. CONCLUSIONS: Menstrual characteristics are strong
predictors of women's self-perceived menopausal status. However, additional
factors, including symptoms and cultural differences in the meaning of specific
bleeding patterns, are also relevant and require further investigation.
PMID- 11006498
TI - Relationships between catastrophic thoughts, perceived control and distress
during menopausal hot flushes: exploring the correlates of a questionnaire
measure.
AB - OBJECTIVES: Many studies have established that highly negative or catastrophic
thoughts about chronic health problems such as pain are associated with greater
distress, lower self-efficacy for dealing with the problem and depressed mood.
This study examined whether highly negative (or 'catastrophic') appraisals of hot
flush experiences were associated with greater distress and lower perceived
control regarding this menopausal problem. DESIGN: A postal survey was carried
out, with a follow-up 12 months later. METHODS: Two questionnaires were initially
completed by a volunteer sample of 61 women currently experiencing hot flushes. A
mixture of qualitative and quantitative data were collected, including a
Catastrophic Thoughts Questionnaire (CTQ) measure of catastrophic thoughts, based
in part on Rosenstiel AK and Keefe FJ. The use of coping strategies in chronic
low back pain patients: relationship to patient characteristics and current
adjustment. Pain 1983;17:33-44. Thirty nine women who continued to report hot
flushes were followed up 12 months later. RESULTS: Ratings to each item of the
CTQ were highly intercorrelated. Women reporting more catastrophic thoughts
tended to be lower in perceived control over flushes. Respondents' reported
distress during hot flushes was more closely related to their frequency of
negative thoughts about the problem, than to perceived control, flush chronicity
or daily frequency of flushes. Over 12 months, respondents showed a highly stable
pattern of catastrophic thoughts, and continued links with levels of distress
during flush episodes. CONCLUSIONS: Cognitive appraisal processes that undermine
coping with other chronic health problems seem also relevant to understanding the
distress triggered by intermittent, unpredictable flush episodes. The findings
imply that women may develop improved tolerance for menopausal flushing through
challenging negative interpretations of the experience.
PMID- 11006499
TI - Effects of estrogen therapy on well-being in postmenopausal women without
vasomotor complaints.
AB - OBJECTIVE: To establish whether estrogen treatment affects well-being in
postmenopausal women without current or previous vasomotor symptoms. DESIGN:
Forty postmenopausal women, aged 45-59 years, without current or previous
vasomotor complaints, were included. They were randomized to masked treatment
with either transdermal 17beta-estradiol 50 microg/24 h or to placebo. At
baseline and after 12 and 14 weeks of treatment, the women completed a
questionnaire which reflects well-being, the Psychological General Well-Being
(PGWB) Index. RESULTS: The women scored high on the PGWB Index, both at baseline
and after 12 and 14 weeks of treatment. There was no significant difference in
well-being according to PGWB Index between the groups treated with estrogen and
placebo, neither at baseline, nor after therapy. Furthermore, there was no
difference in change during therapy between the treatment groups. CONCLUSION:
There is a gradual decline in estrogen during the climacteric, and it is
controversial to which extent this affects women's mental health. The PGWB scores
in this study were high before therapy, reflecting that these women without
previous or current vasomotor complaints represented a selected sample. Neither
short-term estrogen treatment over 12 weeks nor addition with medroxyprogesterone
acetate during 2 weeks improved well-being in postmenopausal women without
vasomotor symptoms who had high well-being at baseline.
PMID- 11006500
TI - Expression of estrogen receptor (ER) in oral mucosa and salivary glands.
AB - OBJECTIVES: To assess the expression of estrogen receptor (ER) in oral mucosa and
salivary glands, buccal mucosal biopsies from ten postmenopausal women (taken
before and during the hormone replacement therapy), as well as, single biopsies
from 20 healthy 19-year-old women were analyzed for ER expression. Salivary gland
biopsies were taken from the minor labial salivary glands (n=6), submandibular
glands (n=5) and parotid gland (n=1) from women at different ages. METHODS: total
RNA extracted from the tissue samples was reverse-transcripted (RT) to single
stranded cDNA, and the RT-polymerase chain reaction (RT-PCR) product was
subjected to nucleotide sequencing to confirm the match with ER cDNA.
Immunohistochemistry (IHC) with a monoclonal ER antibody (ER-ICA, Abbott) and
Western blot analysis with monoclonal antibody against ER-related antigen (ER-D5,
Amersham) were performed on the biopsies taken from the postmenopausal women.
RESULTS: ER mRNA was expressed in 18/20 (90%) and 20/20 (100%) of the mucosal
biopsies in the postmenopausal and 19-year-old women, respectively. The
expression of mRNA was detected in all the submandibular gland samples, in the
single parotid gland, as well as, in 4/6 (67%) of the labial glands. ER
expression could not be detected by IHC, indicating either a very low level of
expressed protein or difficulties in recognizing the epitopes by IHC. However,
Western blot demonstrated 8/8 (100%) of the mucosal biopsies of postmenopausal
women positive for ER-related antigen. CONCLUSIONS: the presence of ER mRNA and
immunoreactive ER protein suggests that estrogens have a biological role in oral
mucosa and salivary glands.
PMID- 11006501
TI - Effects of norethisterone acetate addition to estradiol in long term HRT.
AB - OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of
hormone replacement therapy (HRT) among postmenopausal women living in the Lund
area of Southern Sweden and to analyze treatment effects in different types or
routes of HRT administration, as well as to compare with unopposed estrogen
therapy. METHOD: in an ongoing, large population-based, prospective cohort study,
this interim analysis included 3900 women. Of them, 693 postmenopausal women were
eligible in the present analyses as they continued to use one of the four
commercial HRT products for at least 2-3 years, i.e. continuous oral estradiol
(E(2)) 2 mg+norethisterone acetate (NETA) 1 mg (CON-O), sequential oral estradiol
2 mg + norethisterone acetate 1 mg (CYC-O), sequential transdermal estradiol 50
microg + norethisterone acetate 250 microg (CYC-TRANS) and estradiol monotherapy.
These women completed one generic questionnaire and one specific 'hormonal'
questionnaire, as well as a personal interview pertaining to socio-demographics,
detailed status of HRT use, and therapeutic efficacy and untoward side-effects by
HRT. RESULTS: comparing the three combined E(2)+NETA groups with E(2)
monotherapy, the beneficial effects on sexual desire and emotional well-being
were significantly less in the combined groups than in E(2) monotherapy group.
There was no significant difference regarding the negative side-effects between
the groups. No significant difference was found between CON-O and CYC-O groups
either in positive effects or in negative side-effects. A higher prevalence of
positive effects was found in CYC-TRANS group than that in CYC-O group,
especially in amelioration of sleep and urinary symptoms. Higher odd ratios of
negative effects by HRT, such as irregular bleeds, weight gain, food craving and
skin disorders were also found in CYC-TRANS group. CONCLUSION: in long-term HRT
administration, the addition of a progestogen in HRT could compromise the
beneficial effects of estradiol, particularly, the effects on women's emotional
well being and psychosexual functioning. Administration of NETA continuously and
sequentially had similar therapeutic efficacy and tolerability. More marked
positive effects, such as improving of sleep and urinary symptoms, as well as
nuisance side-effects, i.e. irregular bleeds, weight gain, food craving and skin
disorders were encountered by the women using sequential transdermal regimen
PMID- 11006502
TI - Collagen: image processing and quantitative ultrastructural studies
PMID- 11006503
TI - Type V collagen: heterotypic type I/V collagen interactions in the regulation of
fibril assembly.
AB - Type V collagen is a quantitatively minor fibrillar collagen with a broad tissue
distribution. The most common type V collagen isoform is alpha1(V)(2) alpha2(V)
found in cornea. However, other isoforms exist, including an
[alpha1(V)alpha2(V)alpha3(V)] form, an alpha1(V)(3) homotrimer and hybrid type
V/XI forms. The functional role and fibrillar organization of these isoforms is
not understood. In the cornea, type V collagen has a key role in the regulation
of initial fibril assembly. Type I and type V collagen co-assemble into
heterotypic fibrils. The entire triple-helical domain of the type V collagen
molecules is buried within the fibril and type I collagen molecules are present
along the fibril surface. The retained NH(2)-terminal domains of the type V
collagen are exposed at the surface, extending outward through the gap zones. The
molecular model of the NH(2)-terminal domain indicates that the short alpha
helical region is a flexible hinge-like region allowing the peptide to project
away from the major axis of the molecule; the short triple-helical regions serve
as an extension through the hole zone, placing the tyrosine-rich domain at the
surface. The assembly of early, immature fibril intermediates (segments) is
regulated by the NH(2)-terminal domain of type V collagen. These NH(2)-terminal
domains alter accretion of collagen molecules onto fibrils and therefore lateral
growth. A critical density would favor the initiation of new fibrils rather than
the continued growth of existing fibrils. Other type V collagen isoforms are
likely to have an important role in non-cornea tissues. This role may be mediated
by supramolecular aggregates different from those in the corneal stroma or by an
alteration of the interactions mediated by tissue-specific type V collagen
domains generated by different isoforms or aggregate structures. Presumably, the
aggregate structure or specific domains are involved in the regionalization of
fibril-associated macromolecules necessary for the tissue-specific regulation of
later fibril growth and matrix assembly stages.
PMID- 11006504
TI - Fourier and power law analysis of structural complexity in cornea and lens.
AB - The ordered pattern of type I collagen fibrils in the transparent cornea is an
example of specialization in the formation of functional ultrastructure. In
contrast, the disordered and amorphous distribution of cytoplasmic proteins in
the transparent lens resembles the structure of most cells. While the
organization of cytoplasmic proteins is often considered to be random, the
compartmentalization of functional proteins in biological cells and the
organization provided by cytoskeletal elements suggests that non-random patterns
of organization are common. Attempts to quantify disordered, amorphous patterns
of ultrastructure in cells and tissues have been unsuccessful, in part, because
the cellular organization of structural proteins including collagen, keratin,
cytoskeletal and crystallin proteins is complex. Characterization of the complex
patterns observed in electron micrographs is a fundamental problem in structural
biology. This paper reviews the use of Fourier and power law analyses of electron
micrographs of cornea and lens as models for ordered and disordered
ultrastructure of cells and tissues.
PMID- 11006505
TI - Collagen structure and functional implications.
AB - The bio-mechanical requirements to which the connective tissue is subjected
suggest that a causal correlation exist between the substructure and the collagen
fibril function. We discuss the relationship between the inner structure of
collagen fibrils, their diameter, their spatial layout and the functional
requirements they have to withstand, and suggest that collagen fibrils may belong
to two different forms indicated as "T-type" and "C-type". The first class,
consisting of large, heterogeneous fibrils, parallely tightly packed, subjected
to tensile stress along their axis is found in highly tensile structures such as
tendons, ligaments and bone. The other class, consisting of small, homogeneous
fibrils, helically arranged, resisting multidirectional stresses, is mostly
present within highly compliant tissues such as blood vessel walls, skin and
nerve sheaths. What causes these architectures to appear is discussed in detail
in this review.
PMID- 11006506
TI - Corneal and scleral collagens--a microscopist's perspective.
AB - This paper reviews our existing understanding of the distribution and
organisation of collagen types within the corneal and scleral stroma from a
microscopical perspective. The contribution of various types of light microscopy,
electron microscopy and atomic force microscopy to this field are separately
discussed. Light microscopy was used in the earliest studies of the cornea and
lead to the first description of the lamellar structure of the stroma. More
recently polarised light microscopy has been used to obtain specific information
on fibril orientation within individual lamellae. Light microscope
immunolabelling techniques have been utilised to determine the distribution of
several collagen types within the cornea and sclera, while recent developments in
confocal microscopy have allowed detailed observations to be made on live cornea.
Scanning electron microscopy has proved useful in determining the 3D organisation
of lamellae within both corneal and scleral stroma. The transmission electron
microscope was responsible for first revealing the regular diameter and high
degree of order of the collagen fibrils present in the corneal stroma and
contrasting this with the irregular diameter of fibrils present in sclera. This
finding lead directly to the formulation of a theory of corneal transparency
based on the uniformity of fibril diameter and packing. The use of specialised
stains such as cuprolinic blue allowed direct observation of the
glycosaminoglycan chains on proteoglycan molecules in cornea and sclera. These
images allowed the binding sites of the proteoglycans along the collagen fibrils
to be identified and provided convincing evidence for the importance of the
proteoglycan molecules in collagen fibril organisation. Immunogold labelling has
been used to map the distribution of several collagen types within the corneal
and scleral stroma at the ultrastructural level and provided critical evidence
for the role of type V collagen in the regulation of fibril diameter within the
cornea. Specialised freezing-etching techniques have revealed the surface
features of the collagen fibrils in corneal stroma, indicating clearly the
presence of crossbridge structures between fibrils. The technique of rotary
shadowing has been used to determine the conformation of several collagen types.
In more recent years atomic force microscopy has been applied to the study of the
corneal stroma. It has largely confirmed the observations made by the
transmission electron microscope and provided independent evidence of crossbridge
structures between the collagen fibres in cornea and sclera. The full potential
of this technique has yet to be realised.
PMID- 11006507
TI - STEM/TEM studies of collagen fibril assembly.
AB - Quantitative scanning transmission electron microscopy (STEM), implemented on a
conventional transmission electron microscope with STEM-attachment, has been a
primary tool in our laboratory for the quantitative analysis of collagen fibril
assembly in vivo and in vitro. Using this technique, a precise measurement of
mass per unit length can be made at regular intervals along a fibril to generate
an axial mass distribution (AMD). This in turn allows the number of collagen
molecules to be calculated for every transverse section of the fibril along its
entire length. All fibrils show a near-linear AMD in their tip regions. Only
fibrils formed in tissue environments, however, show a characteristic abrupt
change in mass slope along their tips. It appears that this tip growth
characteristic is common to fibrils from evolutionarily diverse systems including
vertebrate tendon and the mutable tissues of the echinoderms. Computer models of
collagen fibril assembly have now been developed based on interpretation of the
STEM data. Two alternative models have so far been generated for fibril growth by
accretion; one is based on diffusion limited aggregation (DLA) and the other
based on an interface-limited growth mechanism. Inter-fibrillar fusion can also
contribute to the growth of fibrils in vertebrate tissues and STEM data indicates
the presence of a tight regulation in this process. These models are fundamental
for the hypotheses regarding how cells synthesise and spatially organise an
extracellular matrix (ECM), rich in collagen fibrils.
PMID- 11006508
TI - Structural variations of collagen in normal and pathological tissues: role of
electron microscopy.
AB - The spectrum of ultrastructural appearances assumed by collagen in normal and
pathological tissues is illustrated using techniques of thin section transmission
electron microscopy and computer-assisted analysis. The normal fibrillar collagen
types are described in order to provide a basis for comparing other normal and
abnormal forms. In normal tissues, the anchoring fibril and basal lamina
(basement membrane) represent tissue structures largely containing collagen but
differing significantly in organisation from normal types I to III fibrillar
collagen. In pathological tissue, deviations from normal fine structure are
reflected in abnormal aggregates of collagen fibrils (amianthoid and skeinoid
fibres) and abnormalities in fibril diameter and cross-sectional profile. Fibrous
and segment long-spacing collagen represent two further organisational variants
of collagen, the former found widely in pathological tissues, the latter very
rarely. Much remains to be discovered about these abnormal collagen variants
their mode of formation, the cells that produce them, and their roles. They also
present a challenge for the collagen biologist formulating hypotheses of collagen
fibril assembly and molecular organisation.
PMID- 11006509
TI - Collagen fibril organisation in mammalian vitreous by freeze etch/rotary
shadowing electron microscopy.
AB - Mammalian vitreous gel contains two major network-forming polymeric systems:
long, thin fibrils comprising predominantly type II collagen and a meshwork of
hyaluronan. The gel structure is maintained primarily by the collagen component,
but little is known about the mechanisms of spacing of the collagen fibrils and
of interactions between fibrils to form a stable network. In this study we have
applied the technique of freeze etching/rotary shadowing electron microscopy in
order to reveal the fibrillar network in central, cortical and basal vitreous and
to understand the structural relationship between the collagen fibrils. The
fibrils were arranged side by side in narrow bundles that frequently branched to
link one bundle to another. Only a minor part of the fibrillar network consisted
of segments that had a diameter of a single fibril (16.4nm mean diameter). In
addition, three morphologically distinct filamentous structures were observed
that appeared to form links within the collagen fibrillar network: short, single
interlinking filaments of 7.0nm mean diameter, network-forming filaments of 6.7nm
mean diameter, and longer filaments of 8.2nm mean diameter. All three types of
filamentous structure were removed by digestion of the vitreous gels with
Streptomyces hyaluronan lyase prior to freeze etching, indicating that these
structures contain or are stabilised by hyaluronan. These filamentous structures
may contribute to the structural stability of the vitreous gel.
PMID- 11006510
TI - Collagen as a model system to investigate the use of aspirin as an inhibitor of
protein glycation and crosslinking.
AB - Aspirin has been shown to be a powerful inhibitor of post-Amadori Maillard
reactions, although the exact mechanism of this action remains unclear. We have
used corneal and scleral collagen as a model system: (i) to assess how aspirin,
either alone or in combination with sugars, affects the surface charge
distribution along the collagen fibrils; (ii) to see how sugars and/or aspirin
affect the swelling properties of the cornea; and (iii) to see if sugars and/or
aspirin change the distribution of water within the corneal stroma as the tissue
swells. Charge changes were detected by examining changes in the uptake of
phosphotungstate ions as seen in the electron microscope. Swelling was measured
by monitoring the uptake of water as a function of swelling time, and water
distribution was determined by using synchrotron X-ray diffraction to follow
changes in the interfibrillar Bragg spacing as the cornea swells. Aspirin has a
marked effect on the positive staining pattern of scleral collagen. This is
different to the changes in stain uptake produced by glycation. Incubation with
both sugars and aspirin showed that the sugar binding takes precedence over the
effects of aspirin which, in turn, suggests that protein acetylation by aspirin
is unlikely under these circumstances. However, aspirin completely suppresses
corneal swelling. Even when the aspirin is removed, swelling in distilled water
is reduced, and this is accompanied by changes in the water distribution. The
results suggest that water is more evenly distributed in aspirin-treated corneas
that are subsequently swollen than in swollen glycated corneas. Fructation,
glucation and ribation on their own have little effect on the uptake of water as
the cornea swells. This suggests that any sugar-derived crosslinks formed at this
stage do not limit swelling.
PMID- 11006511
TI - The fibril structure of type V collagen triple-helical domain.
AB - Although the triple-helical structure of fibrillar collagen is regarded in
general as being quite similar, each type of collagen molecule has inherent
characteristics in the triple-helical domain. Few studies have ever been
performed in terms of the aggregate structure of the triple-helical domain of
fibrillar collagen. Reconstituted aggregates from the purified triple-helical
domain of each type of fibrillar collagen might amplify the subtle differences in
the structural characteristics of each type of collagen molecule. In this study,
the reconstituted aggregate structure of pepsin-treated type V collagen (type Vp
collagen), that is, virtually its triple-helical domain was characterized by
transmission electron microscopy. Pepsin-treated type I (type Ip) and type II
(type IIp) collagen were compared with type Vp collagen. Unique features of the
aggregate structure of the triple-helical domain of the type V collagen can be
summarized as follows:These results suggested that the lateral packing of the
triple-helical domain of type V collagen is determined by its molecular
structure. The characteristics of type Vp collagen fibrils might be explained by
their characteristic amino acid composition. A significant feature of the triple
helical domain of type V collagen is the high content of glycosylated
hydroxylysine residues. Molecular model building of the collagenous structure
suggests that a change in surface roughness is conspicuous by incorporating the
glycosylated hydroxylysine residues. More than a ten-fold content of bulky
glycosylated hydroxylysine residues in type V collagen compared to that of type I
might have a significant influence on both the intermolecular and interfibrillar
interactions of the triple-helical domain of type V collagen molecule.
PMID- 11006512
TI - Thermally labile domains in the collagen molecule.
AB - We have proposed that the denaturation kinetics of the characteristic sharp
melting point of the collagen molecules is an irreversible rate rather than an
equilibrium process as previously believed. This leads to the concept of domains
of variable thermal stability along the length of the molecule. We have
identified the major thermally labile domains from which the denaturation process
is initiated as hydroxyproline deficient sequences of 65, 65 and 59 residues near
the carboxy terminus in fibrillar collagen types I, II and III, respectively.
These domains differ in that there is a single hydroxyproline in the type II
domain and two hydroxyprolines in the type III domain. Similar sized domains are
conserved in these collagen types across species including amphibians and
invertebrates. The effective size of the domain is reduced in the fibrillar
aggregates to 26 residues due to the interaction with adjacent molecules and
because of the precise quarter-staggered alignment of the molecules the domains
are located in the gap region. This spatial confinement within the lattice of the
fibre leads to the significant increase in denaturation temperature of the fibre
compared to the molecule. These labile domains have also been located in
molecules that form the non-fibrillar type IV basement membrane collagens and the
fibril-associated aggregates such as type IX. Based on the location of the
different domains in type IX we have proposed a different arrangement of the type
IX on the type II fibril. The model stresses the importance of hydroxyproline in
stabilising the triple helix and supports the concept of hydrogen-bonded water
bridges originally proposed from X-ray diffraction studies in contrast to other
studies indicating water-bridges do not play a role in stabilising the collagen
molecule.
PMID- 11006513
TI - Diameter distributions of collagenous tissues in relation to sex. A quantitative
ultrastructural study.
AB - A number of factors have been implicated in the regulation of collagen fibril
diameter. Electron microscopy analysis was used to investigate the role of sex on
fibril diameter. Female mouse skin collagen fibrils' mean diameter values were
significantly smaller than those from the male, independent of age. In addition,
the female rabbit collagen fibrils had a marked decrease in the mean diameter
compared to male, in all the tissues examined (skin, liver, and bone). These data
suggest that the collagen fibril diameter is related to sex.
PMID- 11006514
TI - Measurement of the axial periodicity of collagen fibrils using an image
processing method.
AB - In this paper, a method is described based on a computer-aided analysis of
electron-optical images of collagen fibrils from various tissues, in order to
determine the axial periodicity of such fibrils. The method gives information at
a level of 2-3nm.
PMID- 11006515
TI - A study of fibrous long spacing collagen ultrastructure and assembly by atomic
force microscopy.
AB - Fibrous long spacing collagen (FLS) fibrils are collagen fibrils that display a
banding with periodicity greater than the 67nm periodicity of native collagen.
FLS fibrils can be formed in vitro by addition of alpha(1)-acid glycoprotein to
an acidified solution of monomeric collagen, followed by dialysis of the
resulting mixture. We have investigated the ultrastructure of FLS fibrils formed
in vitro using the atomic force microscope (AFM). The majority of the fibrils
imaged showed typical diameters of approximately 150nm and had a distinct banding
pattern with a approximately 250nm periodicity. However, we have also observed an
additional type of FLS fibril, which is characterized by a secondary banding
pattern surrounding the primary bands. These results are compared with those
obtained in past investigations of FLS ultrastructure carried out using the
transmission electron microscope (TEM). The importance of the fibril's surface
topography in TEM staining patterns is discussed. Images of FLS fibrils in
various stages of assembly have also been collected, and the implications of
these images in determining the mechanism of assembly and the formation of the
characteristic banding pattern of the fibrils is discussed.
PMID- 11006516
TI - Ultrastructure and assembly of segmental long spacing collagen studied by atomic
force microscopy.
AB - The in vitro formation of segmental long spacing (SLS) collagen as induced by the
addition of ATP to acidified Type I collagen solutions has been examined with the
atomic force microscope (AFM). AFM images obtained suggest that the assembly
proceeds in a stepwise manner, through an intermediate stage of oligomers, which
then associate laterally to form the so-called "SLS crystallites". Attempts to
induce SLS formation by the addition of other polyanionic species to monomeric
collagen solutions met with mixed success; ATP-gamma-S and GTP produced SLS
crystallites, whereas inorganic phosphate and other polyanionic dyes did not.
This indicates that the formation of SLS cannot simply be attributed to the
negation of positive charges believed to be located on the end of the collagen
monomer, but rather it is a complex function of the structure and charge of both
the collagen monomer and polyanion.
PMID- 11006517
TI - Changing trends
PMID- 11006518
TI - Targeting TGF could counter diabetic nephropathy.
PMID- 11006519
TI - Kaposi's sarcoma-associated virus mounts novel attack on immune system.
PMID- 11006520
TI - Vaccine against breast and ovarian cancer still on the horizon.
PMID- 11006521
TI - Another piece in the hypertension puzzle.
PMID- 11006522
TI - Nurture leads the race in the control of cancer.
PMID- 11006523
TI - Communication genes clustered on 7q31.
PMID- 11006524
TI - Memory cells in the immune system: how to be efficient, even in small numbers.
PMID- 11006525
TI - Peptic ulcer irony.
PMID- 11006526
TI - Ageing and the brain, a first glimpse at age-induced altered gene expression.
PMID- 11006527
TI - Protein aggregation in Huntington's and Parkinson's disease: implications for
therapy.
AB - The accumulation of highly insoluble intracellular protein aggregates in neuronal
inclusions is a hallmark of Huntington's disease (HD) and Parkinson's disease
(PD) as well as several other late-onset neurodegenerative disorders. The
aggregates formed in vitro and in vivo generally have a fibrillar morphology,
consist of individual beta-strands and are resistant to proteolytic degradation.
Although the causal relationship between aggregate formation and disease remains
to be proven, the gradual deposition of mutant protein in neurons is consistent
with the late-onset and progressive nature of symptoms. Recently, circumstantial
evidence from mouse and Drosophila model systems suggests that abnormal protein
folding and aggregation play a key role in the pathogenesis of both HD and PD.
Therefore, a detailed understanding of the molecular mechanisms of protein
aggregation and its effects on neuronal cell death could open new opportunities
for therapy.
PMID- 11006528
TI - Secretases as targets for the treatment of Alzheimer's disease.
AB - Alzheimer's disease (AD) is the major cause of dementia in most developed
countries. Treatment to modify this disease is currently unavailable, but needed
urgently. The amyloid-cascade hypothesis proposes that amyloid beta-peptide
(Abeta), found in the plaques characteristic of AD, plays an early, critical role
in the disease process. It follows that preventing the generation of Abeta could
be therapeutically useful in all cases of AD. Inhibition of the secretases that
produce Abeta from a large precursor protein is the main approach to achieve this
goal.
PMID- 11006529
TI - RAS inhibitors: potential for cancer therapeutics.
AB - As RAS oncoproteins play a major role in human malignancy, inhibiting RAS
function is a promising approach for developing anticancer therapies. Among these
approaches are agents such as farnesyltransferase inhibitors (FTIs) and the
nontoxic farnesylcysteine analogue farnesylthiosalicylic acid (FTS) that
dislodges all RAS isoforms from the membrane, as well as methods to restore
regulation of RAS-GTP levels and to alter the interaction of RAS-GTP with
downstream targets.
PMID- 11006530
TI - X-linked severe combined immunodeficiency: from molecular cause to gene therapy
within seven years.
AB - X-linked severe combined immunodeficiency (XSCID) is the most common form of
SCID. The discovery of the genetic defect in this disease, namely mutations in
the gene encoding the common cytokine receptor gamma chain, gammac, was reported
just over seven years ago. In the subsequent period, a tremendous amount of
knowledge about the biology and function of this protein has been generated.
Moreover, gammac-knockout mice have been generated and their immune systems
successfully reconstituted by gene therapy. Furthermore, initial attempts at
using gene therapy to treat patients with XSCID have been successful for more
than ten months, making this disease perhaps the most promising to date for
treatment with such a strategy.
PMID- 11006531
TI - Murine models of malignant melanoma.
PMID- 11006533
TI - Analytical techniques - from proteome analysis to mechanical phenotypes of
multiprotein assemblies. Editorial overview
PMID- 11006532
TI - Web alert.
AB - A selection of World Wide Web sites relevant to papers published in this issue of
Current Opinion in Chemical Biology.
PMID- 11006534
TI - Mass spectrometry and proteomics.
AB - Proteomics is the systematic analysis of the proteins expressed by a cell or
tissue, and mass spectrometry is its essential analytical tool. In the past two
years, incremental advances in standard proteome technology have increased the
speed of protein identification with higher levels of automation and sensitivity.
Furthermore, new approaches have provided landmark advances in determining
functionally relevant properties of proteins, including their quantity and
involvement within protein complexes.
PMID- 11006535
TI - Advances in multiple wavelength anomalous diffraction crystallography.
AB - In only a few years, multiple wavelength anomalous diffraction (MAD) phasing has
advanced from an esoteric technique used in only a few favorable cases to the
method of choice for solving new macromolecular structures. Before 1994, MAD
phasing had been used for fewer than a dozen new structure determinations. In
1999 alone, well over 100 new structures were determined by MAD phasing. The
meteoric rise in MAD applications resulted from the availability of new
synchrotron beamlines, equipped with low bandpass optics, fast readout detectors,
cryogenic cooling and user-friendly interfaces. The power of MAD phasing has been
amplified by the availability of new computer programs for locating the positions
of the anomalous scattering atoms and for calculating phases from the
experimental data. Phasing by anomalous scattering techniques has been applied to
structures as large as 640 kDa and 120 selenium atoms in the asymmetric unit. The
practical size limitation for application of MAD phasing techniques has not yet
been encountered.
PMID- 11006536
TI - Solid-state NMR as a probe of amyloid fibril structure.
AB - Amyloid fibrils are intrinsically noncrystalline, insoluble, high-molecular
weight aggregates of peptides and proteins, with considerable biomedical and
biophysical significance. Solid-state NMR techniques are uniquely capable of
providing high-resolution, site-specific structural constraints for amyloid
fibrils, at the level of specific interatomic distances and torsion angles. So
far, a relatively small number of solid-state NMR studies of amyloid fibrils have
been reported. These have addressed issues about the supramolecular organization
of beta-sheets in the fibrils and the peptide conformation in the fibrils, and
have concentrated on the beta-amyloid peptide of Alzheimer's disease. Many
additional applications of solid-state NMR to amyloid fibrils from a variety of
sources are anticipated in the near future, as these systems are ideally suited
for the technique and are of widespread current interest.
PMID- 11006537
TI - Fluorescence resonance energy transfer as a structural tool for nucleic acids.
AB - Fluorescence resonance energy transfer is a spectroscopic method that provides
distance information on macromolecules in solution in the range 20-80 A. It is
particularly suited to the analysis of the global structure of nucleic acids
because the long-range distance information provides constraints when modelling
these important structures. The application of fluorescence resonance energy
transfer to nucleic acid structure has seen a resurgence of interest in the past
decade, which continues to increase. An especially exciting development is the
recent extension to single-molecule studies.
PMID- 11006538
TI - Vibrational spectroscopy as a tool for probing protein function.
AB - Vibrational spectroscopy has become increasingly important as a tool for
understanding the mechanisms of photosystem II, phytochrome and terminal
oxidases. More general enzymatic or receptor systems have been studied, opening a
new field of applications. Femtosecond infrared pump/probe studies of the
important amide-I band seem to provide a basis for its molecular and structural
interpretation.
PMID- 11006540
TI - Mechanisms. Mechanisms Of catalysis - macroscopic and microscopic progress
PMID- 11006539
TI - Force spectroscopy with single bio-molecules.
AB - For many biological molecules, force is an important functional and structural
parameter. With the rapidly growing knowledge about the relation between
structure, function, and force, single-molecule force spectroscopy has become a
versatile analytical tool for the structural and functional investigation of
single bio-molecules in their native environments. Within the past year, detailed
insights into binding potentials of receptor ligand pairs, protein folding
pathways, molecular motors, DNA mechanics and the functioning of DNA-binding
agents (such as proteins and drugs), as well as the function of molecular motors,
have been obtained.
PMID- 11006542
TI - Computational enzymology.
AB - Recent advances in computational methods and the availability of fast, affordable
computers have made the modeling of enzymatic reactions practical. The remaining
challenges include achieving the accuracy level at which thermodynamic parameters
and kinetic constants for different substrates, mutant enzymes, or in the
presence of allosteric effectors can be predicted quantitatively.
PMID- 11006541
TI - Native disulfide bond formation in proteins.
AB - Native disulfide bond formation is critical for the proper folding of many
proteins. Recent studies using newly identified protein oxidants, folding
catalysts, and mutant cells provide insight into the mechanism of oxidative
protein folding in vivo. This insight promises new strategies for more efficient
protein production.
PMID- 11006543
TI - Cyclooxygenase mechanisms.
AB - Several advances have occurred in the past year in our understanding of
cyclooxygenase catalysis. The role of specific heme oxidation states in the
formation of catalytically competent tyrosyl radicals has been defined; the
identity of physiological hydroperoxide activators has been established; and the
participation of individual amino acids in substrate binding and oxygenation has
been elucidated.
PMID- 11006544
TI - Ribonuclease P: a ribonucleoprotein enzyme.
AB - The ribonucleoprotein ribonuclease P catalyzes the hydrolysis of a specific
phosphodiester bond in precursor tRNA to form the mature 5' end of tRNA. Recent
studies have shed light on the structures of RNase-P-RNA-P-protein and RNase-P
RNA-precursor-tRNA complexes, as well as on the positions of catalytic metal
ions, emphasizing the importance of the structure to the catalytic function.
PMID- 11006545
TI - Nitrogenase: standing at the crossroads.
AB - Nitrogenase catalyzes the ATP-dependent reduction of dinitrogen to ammonia, which
is central to the process of biological nitrogen fixation. Recent progress
towards establishing the mechanism of action of this complex metalloenzyme
reflects the contributions of a combination of structural, biochemical,
spectroscopic, synthetic and theoretical approaches to a challenging problem with
implications for a range of biochemical and chemical systems.
PMID- 11006546
TI - Modular evolution of the purine biosynthetic pathway.
AB - Structural studies, sequence alignments, and biochemistry have provided new
insights into the evolution of the purine biosynthetic pathway. The importance of
chemistry, the binding of ribose 5-phosphate (common to all purine biosynthetic
intermediates), and transient protein-protein interactions in channeling of
chemically unstable intermediates have all been examined in the past few years.
PMID- 11006547
TI - Glycosidase mechanisms.
AB - Insights into glycosidase mechanisms have come from X-ray crystallographic
studies on complexes with substrate analogs and inhibitors, representing all the
intermediate species along the reaction coordinate. Site-directed mutagenesis
continues to play a significant role in understanding mechanisms, but is also
proving important in generating glycosidases of modified mechanism or
specificity.
PMID- 11006548
TI - Mechanisms of DNA replication.
AB - Advances in recent years have led to exciting new ideas about the initiation,
regulation and coordination of DNA replication. Structural studies have yielded
fascinating glimpses of replisome action. In addition, the involvement of
replication proteins in other cellular processes has blurred the lines between
replication, repair and recombination.
PMID- 11006549
TI - Uequiv: its past, present and future.
AB - The reporting of U(equiv) and its standard uncertainty has a chequered history.
In spite of the recommendation of the IUCr Commission on Journals that authors
use the definition of U(equiv) of their own choice, possibly without standard
uncertainties, there still seems to be some confusion amongst referees and
editors about the status of this derived parameter. It is shown that neither of
the common definitions are very useful, and that the standard uncertainty
computed from the refinement normal matrix is almost worthless. A potential
alternative derived parameter is proposed.
PMID- 11006550
TI - Architecture of crystal structures from square planes.
AB - The crystal structures of ordered b.c.c. (body-centered cubic), f.c. c. (face
centered cubic) or primitive cubic alloys AxBy and related NaCl, ZnS or CaF(2)
derivative structures are characterized by the self-coordination numbers T(1),
T(2) of the A atoms with A atoms. Structures with identical T(1) and T(2) values
for all A atoms are at the corners of T(1) and T(2) structure maps, and can be
analyzed for attractive or repulsive interactions of A atoms. Most observed
structures are at the borders of the structure map and can be obtained by
approximately 10 different combinations of structural units. The different
combination mechanisms explain e.g. the shear structures of CuAu II or Nb(2)O(5)
and the occurrence of vacancies in NaCl-related structures like NbO.
PMID- 11006551
TI - Refinement of framework disorder in dehydrated CaA zeolite from single-crystal
synchrotron data.
AB - An accurate knowledge of zeolite structure is required for understanding their
selective sorption capacities and their catalytic properties. In particular, the
positions of the exchangeable cations and their interactions with the framework
are essential. The present study deals with the accurate crystal structure
determination of a fully exchanged and fully dehydrated CaA zeolite
(Ca(48)Al(96)Si(96)O(384), Fm3c, a = 24.47 A) using single-crystal high
resolution synchrotron X-ray diffraction [(sin straight theta/lambda)(max) = 1.4
A(-1)]. It is shown that cation exchange severely distorts the skeleton,
especially around the O2 atom. The high-resolution synchrotron data reveal that
this latter O atom is disordered and lies out of the mirror plane it occupies in
other A-type zeolites. This feature is related to that observed for Ca(2+)
cations.
PMID- 11006552
TI - X-ray diffraction study of K3NdSi7O17: a new framework silicate with a linear Si
O-Si bond.
AB - Hydrothermal investigations in the high-silica region of the K(2)O-Nd(2)O(3)
SiO(2) system, carried out in a search for novel fast-ion conductors (FICs),
yielded the new compound tripotassium neodymium heptasilicate, K(3)NdSi(7)O(17).
Single-crystal X-ray methods revealed that K(3)NdSi(7)O(17) crystallizes in space
group P3, has lattice constants a = 16.131 (2) and c = 7.7146 (19) A, Z = 4, and
22 atoms in the asymmetric unit. Refinement was carried out to a residual, R(F),
of 0.0253 and a weighted residual, wR(F(2)), of 0.0702 using anisotropic
displacement parameters for all atoms. The silicate anion forms an interrupted
framework, within which both Nd octahedra and K polyhedra are situated. The
structure is unusual in that it contains a symmetry-constrained Si-O-Si bond
angle of 180 degrees. No isomorphs to K(3)NdSi(7)O(17) are known.
PMID- 11006553
TI - Twinning and defects in N-Nb2O5.
AB - N-Nb(2)O(5) [C2/m (No. 12), a = 28.51, b = 3.830 and c = 17.48 A, and beta =
124.8 degrees ] has been investigated by means of selected-area electron
diffraction (SAED) and high-resolution transmission electron microscopy (HRTEM).
N-Nb(2)O(5) is domain twinned, with the twin plane perpendicular to the c* axis.
The domains are rather small and the domain twinning can sometimes be best
explained as stacking faults. A second type of coherent twinning at an angle of
90 degrees to the other two domain directions was also found. These domains are
linked together by areas containing blocks of different sizes, similar to the
disordered block arrangement observed in M-Nb(2)O(5).
PMID- 11006554
TI - Synchrotron X-ray analysis of RbTiOAsO4.
AB - Structure factors for rubidium oxotitanium arsenate, RbTiOAsO(4), were measured
at 293 K with focused synchrotron X-radiation [lambda = 0.7500 (9) A] using a
fast avalanche photodiode counter. The accurate synchrotron single-crystal data
are of sufficient quality and resolution to detect the splitting positions of the
Rb cations at room temperature. Strong accumulation of the Deltarho difference
charge density near the Rb atoms at a distance of approximately 0.5 A in the -c
direction can be attributed to the partial occupancy of additional sites related
by pseudosymmetry. This type of static and/or dynamic disorder is temperature
dependent and seems to be universal for the KTiOPO(4) family of compounds. The
best modelling of the experimental data was obtained with the Rb atom in split
positions described within the harmonic approximation and the multipole functions
for the other atoms. The Deltarho density features in the Ti-O and As-O covalent
bonds can be related to the linear and non-linear susceptibility using bond
polarization theory. The charge-density maps reflect the anisotropy of non-linear
susceptibility, which is larger for directions where locally antisymmetric
components of Deltarho are strong.
PMID- 11006555
TI - Systematic prediction of new ferroelectrics in space group P3.
AB - The current release of the Inorganic Crystal Structure Database contains a total
of 57 entries under space group P3 that correspond to 50 different materials.
There are 21 structures reported with this space group that satisfy the criteria
for ferroelectricity, at a confidence level that depends on the reliability of
the underlying structural determination. One ferroelectric discovered earlier is
also listed. In addition, the database contains 19 entries that probably should
be assigned to a centrosymmetric space group, seven that are polar but probably
not ferroelectric and two that are without atomic coordinates. Seven entries are
either duplicates or present additional structural studies of the same material.
Structures in space group P3 identified as potentially new ferroelectrics include
LiAsCu(0.93), Na(2)UF(6), BiTeI, BaGe(4)O(9), alpha-UMo(2)O(8), Cu(2)SiS(3),
Co(IO(3))(2), Sr(7)Al(12)O(25), KSn(2)F(5), YbIn(2)S(4), Na(5)CrF(2)(PO(4))(2),
Sn(ClO(2))(2)(ClO(4))(6), Eu(3)BWO(9), Li(H(2)O)(4)B(OH)(4).2H(2)O,
Mn(3)V(1/2)(SiO(4))O(OH)(2), Ca(6)(Si(2)O(7))(OH)(6), Na(6.
9(2))[Al(5.6(1))Si(6.4(1))O(24)](S(2)O(3))(1.0(1)).2H(2)O, BaCa(2)In(6)O(12),
Ni(H(2)O)(6)[Sb(OH)(6)](2), Sr(4)Cr(3)O(9) and Cu(5)O(2)(VO(4))(2).CuCl(2).
PMID- 11006556
TI - Crystal structure and charge distribution of YbFeMnO4.
AB - The structure of synthetic YbFeMnO(4) has been refined by single-crystal X-ray
diffraction. Space group R3m, a = 3.4580 (1), c = 25.647 (3) A, V = 265.59 (3)
A(3), Z = 3. Yb is in octahedral coordination, whereas Fe and Mn are disordered
on a single crystallographic type of trigonal bipyramid, in which the cation is
off-centred from the basal plane. Assuming perfect stoichiometry, R(1) = 0.0195,
but the charge distribution (CD) analysis suggests incomplete occupation of the
Yb site. Refinement of the occupancy lowers R(1) to 0.0175, resulting in
s.o.f.(Yb) = 0. 963 (3), with a significant improvement of the Fourier
difference. The electroneutrality is likely preserved through incomplete
occupancy of one of the two oxygen sites: the compound is thus non
stoichiometric, with the formula Yb(0.963)FeMnO(3.945). Another mechanism for
preserving the electroneutrality is the oxidation of a small amount of Mn(2+) to
Mn(3+), which is, however, less probable because of the reduction conditions in
which the sample was synthesized. Both models give a satisfactorily CD result,
but they cannot be definitively distinguished by X-ray data.
PMID- 11006557
TI - Two-dimensional incommensurately modulated structure of (Sr0.13Ca0. 87)2CoSi2O7
crystals.
AB - The incommensurate structure of (Sr(0.13)Ca(0.87))(2)CoSi(2)O(7) at room
temperature has been determined from single-crystal X-ray diffraction data. The
compound has a non-centrosymmetric tetragonal basic cell of a = 7.8743 (4) and c
= 5.0417 (2) A with the space group P4;2(1)m. The refinements of the basic
structure converged to R = 0.038 for 757 main reflections. The two-dimensional
incommensurate structure is characterized by the wavevectors q(1) = 0.286 (3)(a*
+ b*) and q(2) = 0.286 (3)(-a* + b*), where a*, b* are the reciprocal lattice
vectors of the basic structure. With the (3 + 2)-dimensional superspace group
P(p4mg)(P4;2(1)(m)), the refinements converged to R = 0.071 for 1697 observed
reflections (757 main and 940 satellite reflections). The structure is described
in terms of displacement of the atoms, rotation, distortion of CoO(4) and SiO(4)
tetrahedra, and the partial ordering of the Sr and Ca atoms accompanied with the
modulation. Correlated evolution of these features throughout the crystal gives
rise to various oxygen coordination around Ca/Sr. Comparison of the derived
modulated structure to that of Ca(2)CoSi(2)O(7) clarified that the partial
substitution of Ca by large alkaline-earth atoms such as Sr should decrease the
distortion of the polyhedra around the cations.
PMID- 11006558
TI - Isomorphism and pseudosymmetry in 2,6-dichloro- and 2, 6-dibromobenzonitrile.
AB - The title compounds are isomorphous, with two half-molecules in the asymmetric
unit of a monoclinic unit cell in the space group C2/m. For the chloro compound:
a = 18.0525 (8), b = 20.7374 (10), c = 3. 8334 (2) A, beta = 101.143 (1) degrees;
for the bromo compound: a = 18.2269 (15), b = 21.349 (2), c = 3.9663 (3) A, beta
= 101.446 (2) degrees. The dominant intermolecular interactions are between
halogen atoms rather than between halogen and nitrile, as is the case in the
corresponding 2,4,6-trihalobenzonitriles. The molecules pack into layers with a
fourfold pseudosymmetry. The pseudosymmetry appears to be the consequence of
halogen-halogen intermolecular interactions.
PMID- 11006559
TI - Two-dimensional packing and pseudosymmetry.
AB - It is possible to understand, or at least rationalize, the occurrence of
pseusosymmetry elements in some crystals as a consequence of a higher symmetry in
a two-dimensional layer being obscured by the three-dimensional packing of the
layers. Six examples, including both simple compounds and co-crystals and
involving six different symmetries, are described.
PMID- 11006560
TI - Packing modes of (R,R)-tartaric acid esters and amides.
AB - The molecular packing modes of a series of mono- and diamides of (R, R)-tartaric
acid are discussed on the basis of their crystal structures. Derivatives include
combinations of methylester, amide, N-methylamide and N,N-dimethylamide groups,
both symmetrically and asymmetrically substituted. The symmetrically substituted
derivatives do not utilize their C(2) symmetry in the crystal. The packing of
primary tartramides seems to be driven by NH.O=C hydrogen bonds and supplemented
by strong OH.O=C and weak NH.OH bonds. On the other hand, in derivatives
containing methylester and/or methylamide groups OH.OH.O=C hydrogen-bond patterns
seem to dominate. Types of aggregates, characteristic for the investigated
derivatives, include cyclic dimers and ring systems analogous to the dimers, but
formed by two different although complementary functional groups, as well as sets
of chains aligned in a manner resembling the helical arrangement of peptides. The
helices are formed along the screw axis with an identity period of approximately
5 A. In tartramic acids, containing in one molecule both carboxyl and amide
functions, in competition between the two groups to control the molecular
arrangement, the latter dominates, unless it is N-substituted tartramide, in
which case the carboxyl group predominates. Problems with packing, which occur in
some of the structures owing to the steric bulk of the methyl groups, are
overcome by changes in conformation (esters) or by co-crystallization with
solvent water molecules (methylamides and dimethylamides). These derivatives are
also more likely to crystallize with multiple asymmetric units.
PMID- 11006561
TI - Intramolecular hydrogen bonds: common motifs, probabilities of formation and
implications for supramolecular organization.
AB - A systematic survey of the Cambridge Structural Database (CSD) has identified all
intramolecular hydrogen-bonded ring motifs comprising less than 20 atoms with N
and O donors and acceptors. The probabilities of formation P(m) of the 50 most
common motifs, which chiefly comprise five- and six-membered rings, have been
derived by considering the number of intramolecular motifs which could possibly
form. The most probable motifs (P(m) > 85%) are planar conjugated six-membered
rings with a propensity for resonance-assisted hydrogen bonding and these form
the shortest contacts, whilst saturated six-membered rings typically have P(m) <
10%. The influence of intramolecular-motif formation on intermolecular hydrogen
bond formation has been assessed for a planar conjugated model substructure,
showing that a donor-H is considerably less likely to form an intermolecular bond
if it forms an intramolecular one. On the other hand, the involvement of a
carbonyl acceptor in an intramolecular bond does not significantly affect its
ability to act as an intermolecular acceptor and thus carbonyl acceptors display
a substantially higher inclination for bifurcation if one hydrogen bond is
intramolecular.
PMID- 11006562
TI - Graph-set and packing analysis of hydrogen-bonded networks in polyamide
structures in the Cambridge Structural Database.
AB - The hydrogen-bond networks and crystal packing of 81 unique secondary di- and
polyamides in the Cambridge Structural Database are investigated. Graph-set
analysis, as implemented in the RPluto program, is used to classify network
motifs. These have been rationalized in terms of the relative dispositions of the
amide groups. Peptide and retropeptides exhibit significant conformational
flexibility, which permits alternative hydrogen-bonding patterns. In peptides,
dihedral angles of -psi approximately varphi approximately 105 degrees allow an
antiparallel ladder arrangement, containing rings of either the same or
alternating sizes. For retropeptides, and diamides with an odd number of CH(2)
spacers, this conformation leads to a parallel ladder with rings of equal size.
If varphi approaches -60 degrees and psi 180 degrees, ladders adopt a helical
twist, and if the conformation is distorted further, a three-dimensional network
is usually adopted. Diamides with aromatic or an even number of CH(2) spacers
generally form either antiparallel ladders or sheets, although some exhibit both
polymorphs. Symmetry relationships within and between hydrogen-bonded chains,
ladders and sheets in the crystal packing have also been analysed. Polyamides
form considerably more complex networks, although many of the structural motifs
present in the diamides occur as components of these networks.
PMID- 11006563
TI - Conformational transformation coupled with the order-disorder phase transition in
2-methyl-1,3-cyclohexanedione crystals.
AB - The half-chair conformation of the dynamically disordered molecular ring of 2
methyl-1,3-cyclohexanedione, C(7)H(10)O(2), transforms to a sofa below Tc = 244
K, when the crystal undergoes a continuous phase transition induced by the onset
of halting large-amplitude vibrations of methylene groups C(4)H(2) and C(5)H(2).
The temperature dependence of the crystal structure has been investigated by X
ray diffraction. The Ibam symmetry of the crystal reduces below Tc to space group
Pccn. The mechanism of the phase transition and of the conversion of the ring
conformation is discussed.
PMID- 11006564
TI - N-(6-Amino-3,4-dihydro-3-methyl-5-nitroso-4-oxopyrimidin-2-yl) derivatives of
glycine, valine, serine, threonine and methionine: interplay of molecular,
molecular-electronic and supramolecular structures.
AB - In each of N-(6-amino-3, 4-dihydro-3-methyl-5-nitroso-4-oxopyrimidin-2-yl)valine,
C(10)H(15)N(5)O(4) (3) (orthorhombic, P2(1)2(1)2(1)), N-(6-amino-3, 4-dihydro-3
methyl-5-nitroso-4-oxopyrimidin-2-yl)serine monohydrate, C(8)H(11)N(5)O(5).H(2)O
(4) (orthorhombic, P2(1)2(1)2(1)), and N-(6-amino-3, 4-dihydro-3-methyl-5-nitroso
4-oxopyrimidin-2-yl)threonine, C(9)H(13)N(5)O(5)(5) (monoclinic, P2(1)), the C
nitroso fragments exhibit almost equal C-N and N-O bond lengths: the C-N range is
1. 315 (3)-1.329 (3) A and the N-O range is 1.293 (3)-1.326 (3) A. In each
compound there are also very short intermolecular O-H.O hydrogen bonds, in which
carboxyl groups act as hydrogen-bond donors to the nitrosyl O atoms: the O.O
distances range from 2.440 (2) to 2. 504 (4) A and the O-H.O angles lie between
161 and 163 degrees. An interpretation of the relationship between the unusual
intramolecular bond lengths and the very short intermolecular hydrogen bonds has
been developed based on database analysis and computational modelling. In each of
(3)-(5) there is an extensive network of intermolecular hydrogen bonds,
generating three-dimensional frameworks in (3) and (5), and two-dimensional
sheets in (4).
PMID- 11006565
TI - Conformational preferences and supramolecular aggregation in 2
nitrophenylthiolates: disulfides and thiosulfonates.
AB - In each of the asymmetrically substituted disulfides 2-nitro-4'-methyldiphenyl
disulfide, C(13)H(11)NO(2)S(2) (1), 2-nitro-4'-chlorodiphenyl disulfide,
C(12)H(8)ClNO(2)S(2) (2), 2, 4-dinitro-4'-methyldiphenyl disulfide,
C(13)H(10)N(2)O(4)S(2) (3), and 2,4-dinitrophenyl-2'-methoxycarbonylmethyl
disulfide, C(9)H(8)N(2)O(6)S(2) (4), and in both of the symmetrically substituted
disulfides bis(2-nitrophenyl) disulfide, C(12)H(8)N(2)O(4)S(2) (5), and bis(2
nitro-4-trifluoromethylphenyl) disulfide, C(14)H(6)F(6)N(2)O(4)S(2) (6), the 2
nitro groups are essentially coplanar with the adjacent aryl ring and the S atom
remote from the nitrated aryl ring is also essentially coplanar and transoid to
the nitro group. In S-(2-nitrophenyl) 2-nitrobenzene thiosulfonate,
C(12)H(8)N(2)O(6)S(2) (7), which contains three independent molecules in the
asymmetric unit, all six of the independent nitro groups are twisted out of the
plane of the adjacent aryl rings. The crystal structures of (1)-(3) contain
isolated molecules, that of (4) contains centrosymmetric dimers held together by
C-H.O hydrogen bonds, while in the structures of (5)-(7), respectively, the C-H.O
hydrogen bonds generate one-, two- and three-dimensional arrays. The interplay
between molecular conformation and supramolecular aggregation is discussed.
PMID- 11006566
TI - Ferroelastic structures of n-pentyl-, n- hexyl- and n-nonylammonium
dihydrogenphosphate crystals.
AB - This study reports the structure redeterminations of C(5)H(11)NH(3)(+).H(2)PO(4)(
) (n-pentylammonium dihydrogenphosphate, C5ADP), C(6)H(13)NH(3)(+).H(2)PO(4)(-)
(n-hexylammonium dihydrogenphosphate, C6ADP) and C(9)H(19)NH(3)(+).H(2)PO(4)(-)
(n-nonylammonium dihydrogenphosphate, C9ADP). The structures are monoclinic
(P2(1)/n), belonging to the series of previously studied structures C2ADP-C8ADP
and C10ADP. The structures exhibit reproducible ferroelastic switching. There are
hydrogen bonds between the dihydrogenphosphates and the n-alkylammonium groups.
Among them there are two hydrogen bonds with hydrogens which hop from the donor
to the acceptor oxygens during the ferroelastic switching. C5ADP as well as C3ADP
differ from the other members of the series by packing of the double layers of
the dihydrogenphosphates. Moreover, the packing of n-alkylammonium molecules in
all these structures depends on the parity of the number of atoms in the n
alkylammonium chains. All the samples contained two domains and their structures
were refined as twins.
PMID- 11006567
TI - Orthorhombic tau-Zn-Mg-Dy phase related to a Frank-Kasper type decagonal
quasicrystal.
AB - We report a novel Zn-Mg-Dy phase, denoted as the tau-phase, whose structure is
related to that of the Frank-Kasper type decagonal Zn-Mg-Dy phase, based on
electron diffraction and high-resolution transmission electron microscopy
studies. A plausible atomic model is proposed, which is constructed by two types
of atomic clusters related to those in the Zn(7)Mg(4) crystalline compound.
PMID- 11006568
TI - X-ray structure of barium titanate - missed opportunities.
AB - Anomalous X-ray scattering effects are quite extensive in the noncentrosymmetric
ferroelectric structure of barium titanate, and typical estimates for three
published X-ray diffraction experiments are computed. These data show that the
Bijvoet pairs should not be averaged before least-squares refinement for this
polar crystal with small atomic displacements from a higher symmetric space
group.
PMID- 11006573
TI - Changes in serum and tissue zinc levels in sex hormone-induced prostatic
carcinogenesis in the noble rat.
AB - We investigated the changes in serum and tissue zinc levels in the Noble rat
prostate gland under different pathological conditions induced by the
administration of a combination of testosterone and 17beta-estradiol. The results
showed that there were significant differences in serum zinc values between
normal and hormone-treated rats with prostatic hyperplasia, dysplasia and
prostatic carcinoma (p < 0.05), although there was no significant difference
among rats with different forms of prostatic lesions (i.e. hyperplasia, dysplasia
and prostatic adenocarcinoma). There was also a difference in zinc content
between the lateral prostate (LP), ventral prostate (VP) and dorsal prostate (DP)
in normal rats. The zinc levels of LP were several times greater than those of
either VP or DP (p < 0.01). There was also a great difference in zinc levels
between the normal and the hyperplastic/dysplastic and carcinomatous LP and VP (p
< 0. 05). The levels of zinc in both LP and VP were increased in
hyperplasia/dysplasia and carcinoma. On the other hand, the zinc levels of LP
were much higher than those of VP in hyperplasia/dysplasia and carcinoma (p <
0.01), which may be correlated with the incidence of prostate cancers in these
lobes (i. e. higher in LP and much lower in VP). In contrast, in DP, the levels
of zinc were not affected, which may be correlated with the very low incidence of
carcinoma in this lobe. Our data suggest that the difference in zinc levels among
these lobes reflect the heterogeneity in zinc content in various lobes of the rat
prostate. The growth and development of prostatic lesions in LP and VP may be
positively correlated with the significant increase in tissue zinc levels in
these lobes. On the other hand, the lack of response of DP to carcinogenesis may
be due to its relatively stable low zinc levels. It is suggested that tissue zinc
content may be used as a marker for prostatic lesions, including hyperplasia,
dysplasia and carcinoma, while serum zinc levels may be a useful indicator for
abnormal prostatic growth.
PMID- 11006572
TI - Ascitic growth of a spontaneous transplantable T cell lymphoma induces thymic
involution. 2. Induction of apoptosis in thymocytes.
AB - It has been observed that the progressive ascitic growth of a transplantable T
cell lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL),
induces inhibition of various immune responses and is associated with an
involution of the thymus accompanied by a massive depletion of the cortical
region and alteration in the distribution of thymocytes, with a decrease in
CD4+CD8+, CD4+CD8- and CD4-CD8+ thymocytes. Morphological evaluation of
thymocytes from DL-bearing mice revealed that with the progression of DL, a
majority of thymocytes exhibited morphological features characteristic of
apoptotic cell death, which included contracted cell bodies, condensed, uniformly
circumscribed and densely stained chromatin, and membrane-bound apoptotic bodies
containing one or more nuclear fragments. Quantitative and qualitative analysis
of the DNA extracted from the thymocytes of DL-bearing mice revealed DNA
fragmentation that increased concomitantly with the progression of DL and showed
an oligonucleosomal DNA ladder pattern upon agarose gel electrophoresis, a
hallmark of apoptotic cell death. Attempts to identify apoptotic factor(s) showed
that the serum of DL-bearing mice contained certain soluble factor(s) that
augmented the induction of apoptotis in thymocytes in a time- and dose-dependent
manner. Although DL cells or their products, such as DL-cell-conditioned medium
or DL-cell-free ascitic fluid, could also induce apoptosis of thymocytes in
vitro, the magnitude of the same was consistently lower than that induced by the
serum of DL-bearing mice. Further, elucidation of the mechanism of apoptosis
induction in thymocytes with respect to the involvement of apoptosis-related
genes revealed that the death pathway followed an interleukin-1 beta-converting
enzyme-dependent, Fas-mediated apoptotic cascade, with a concomitant increase in
the protein products of the bax, bad, p53, fas and fasL genes and cleavage of the
23-kD N-terminal fragment of Bcl-2 that exhibited Bax-like death effector
properties.
PMID- 11006574
TI - Synergistic cytotoxic interactions between sodium butyrate, MG132 and
camptothecin in human retinoblastoma Y79 cells.
AB - This paper studies the effects caused in human retinoblastoma Y79 cells by
treatment with combinations of sodium butyrate, the inhibitor of topoisomerase I
camptothecin and the inhibitor of 26S proteasome MG132. The combination of sodium
butyrate and camptothecin resulted in a strong synergistic cytotoxicity, as
revealed by combination indices of 0.77 and 0.52 calculated at IC(50) and IC(75).
Synergistic interactions were also demonstrated for combinations of sodium
butyrate and MG132, camptothecin and MG132 and for a combination of all three
compounds. The cytotoxic effects observed after the combined treatments can be
considered a consequence of apoptosis, as suggested by the appearance of
morphological signals of apoptosis and by the activation of caspase-3 with
degradation of poly-ADP ribose polymerase and lamin B. Treatment of Y79 cells
with sodium butyrate alone lowered the levels of p53, E2F-1 and Bcl-2. The
addition of MG132 to sodium butyrate counteracted the effect on p53 only, while
the addition of camptothecin to sodium butyrate counteracted the effect on both
p53 and E2F-1. The treatment of Y79 cells with the triple combination increased
the level of p53, decreased that of Bcl-2, while the level of E2F-1 was not
modified. We suggest that the effects exerted on the levels of these regulatory
proteins can explain the synergistic interactions demonstrated between sodium
butyrate, camptothecin and MG132.
PMID- 11006575
TI - Syndecan-1-dependent homotypic cell adhesion in HT58 lymphoma cells.
AB - OBJECTIVES: Many cellular functions are controlled by cell-cell and cell-matrix
interactions. It has recently been found that syndecans, transmembrane heparan
sulphate (HS) proteoglycans, can act as receptors or co-receptors and modulate
cell adhesion. Our aim was to study the role of syndecan-1 in the aggregation of
human lymphoma cells, and to investigate its effect on cell survival. METHODS:
Immunocytochemistry, confocal laser scanning microscopy, flow cytometry and
aggregation/reaggregation bio-assays were used on HT58, BL41/95 and Raji lymphoma
cell lines. RESULTS: Bio-assays showed that the aggregation of HT58 cells was
inhibited by heparin, HS, removal of the HS chain and binding of the anti
syndecan-1 monoclonal antibody. In the search for a counter-receptor of syndecan
1, several adhesion molecules were tested, but none of them proved to be the
adhesion partner. In the case of heparitinase/trypsin digestion with long-term
inhibition of HS synthesis (sodium chlorate treatment), the inhibited aggregation
was accompanied by cell cycle arrest and the induction of apoptosis. CONCLUSIONS:
The results obtained showed that surface syndecan-1 expression contributes to
homotypic adhesion. In addition, HS chains, including those on syndecan-1, take
part in the regulation of cell proliferation and active cell death in HT58
lymphoma cells.
PMID- 11006576
TI - Epidermal growth factor receptor immunostaining and epidermal growth factor
receptor-tyrosine kinase activity in proliferative and neoplastic human
endometrium.
AB - Epidermal growth factor receptor (EGFR) expression and EGFR-tyrosine kinase (EGFR
TK) activity were measured in proliferative (n = 12) and neoplastic (n = 31)
human endometrium. Immunoreactivity of EGFR was related to clinicopathological
features, estrogen receptor (ER) and progesterone receptor (PR) status, and
patient outcome. All proliferative and 27 neoplastic specimens expressed the
EGFR. Expression of the EGFR was higher in proliferative endometrium than in
endometrial cancer (p < 0.0001). ER immunostaining was observed in 19 of the
endometrial carcinomas, while PR expression was demonstrated in only 12
neoplastic specimens. EGFR expression was not related to the ER/PR immunostaining
in endometrial carcinomas. Clinicopathological features (age, stage, histological
type, grade or depth of invasion) and clinical outcome were unrelated to EGFR
immunoreactivity. EGFR-TK activity was detected in 29 of 31 endometrial neoplasms
with a 9 times higher mean activity in neoplastic than in proliferative
endometrial specimens. There was no relationship between the EGFR-TK activity and
EGFR immunostaining in human neoplastic endometrium (p = 0.77). A trend towards a
poorer outcome of patients with the EGFR-TK activity above 40 pmol/min/mg was
observed, but was not statistically significant. These results support the view
that the EGFR expression is downregulated in endometrial carcinomas compared to
proliferative endometrial specimens.
PMID- 11006577
TI - Antitumor activity of alpha fetoprotein and epidermal growth factor conjugates in
vitro and in vivo.
AB - Conjugates of carminomycin (Cm) with alpha-fetoprotein (AFP) and epidermal growth
factor (EGF) were prepared and their cytotoxic activities were studied in vitro.
Both conjugates showed cytotoxic activity which exceeded that of free Cm in tumor
cell cultures of MCF-7, SKOV3, QOS, P388 and B16 cells. The antitumor effects of
the conjugates were studied in vivo in mice with subcutaneous tumors of B16 and
P388 cells. The Cm-AFP and Cm-EGF conjugates inhibited tumor growth and
noticeably increased the mean life span in experimental animals. Our results
suggest that the therapeutic activity of Cm can be significantly enhanced by
conjugation to AFP or EGF.
PMID- 11006578
TI - Clinical value of tumor markers for early detection of recurrence in patients
with cervical adenocarcinoma and adenosquamous carcinoma.
AB - OBJECTIVE: The clinical value of tumor markers for early detection of recurrence
was investigated in 32 patients with cervical adenocarcinoma or adenosquamous
carcinoma who had recurrent tumors. METHODS: Serum levels of CA 125, CA 19-9,
carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC), in
addition to clinical status at the time of recurrence were investigated. RESULTS:
Among the 32 patients, 26 had no symptoms at the time of recurrence. In 20
patients, elevated serum levels of tumor markers were the first sign of
recurrence. In 21 patients with recurrent adenocarcinoma, the positive rates were
14% (CA 125), 62% (CA 19-9), 29% (CEA), and 5% (SCC). There were 71% of cases
positive for CA 19-9 and/or CEA. In 11 patients with recurrent adenosquamous
carcinoma, the corresponding positive rates were 37% (CA 125), 46% (CA 19-9), 64%
(CEA), and 55% (SCC), with 100% positive for CA 19-9, CEA, and/or SCC.
CONCLUSIONS: The combination of CA 19-9 and CEA is probably the most promising
for detection of recurrent cervical adenocarcinoma. For adenosquamous carcinoma,
the additional use of SCC is recommended.
PMID- 11006579
TI - Determination of brain and plasma drug concentrations by liquid
chromatography/tandem mass spectrometry.
AB - A method is described for the evaluation of drug concentrations in plasma and
brain from treated rats. The analyte is recovered from plasma or brain homogenate
by liquid-liquid extraction and subsequently analyzed by liquid
chromatography/tandem mass spectrometry (LC/MS/MS). A simple experimental
protocol renders the procedure valuable for obtaining information rapidly on
brain penetration and plasma exposure of specific classes of compounds. This
methodology has been applied to evaluate brain penetration with 30 different
compounds from the same discovery program. In an attempt to increase throughput
in our screening efforts, mixture dosing was evaluated. Results from single
compound administration were compared with results following administration of a
mixture of four compounds. Preliminary results, with specific classes of
compounds, show no major differences (ranking order) in brain or plasma
concentrations between mixture dosing and single compound administration,
suggesting that mixture dosing could be applicable to brain penetration studies
in the drug discovery phase.
PMID- 11006580
TI - Evaluation of the metal binding properties of the histidine-rich antimicrobial
peptides histatin 3 and 5 by electrospray ionization mass spectrometry.
AB - Electrospray ionization mass spectrometry (ESI-MS) was used to investigate metal
ion interactions with salivary peptides histatin 3 (H3) and histatin 5 (H5).
Conformational changes of these peptides in the presence of metal ions were
studied using circular dichroism spectroscopy. H3 and H5 formed high affinity
complexes with Cu(2+) and Ni(2+) and, to a lesser extent, with Zn(2+). Both
peptides show the potential for multiple binding sites for Cu(2+) and Ni(2+) and
only a single strong binding site for Zn(2+). The binding of a third Cu(2+) ion
to H3 seems to enable the binding of a fourth ion to H3. The binding of a second
and third Ni(2+) ion to H5 has a similar effect in enabling the binding of a
fourth ion. None of the metal ions examined stabilized a regular secondary
structure for either peptide. Subtle changes in overall conformation are seen
with the addition of Cu(2+) to both H3 and H5.
PMID- 11006581
TI - Regioselective synthesis and electron impact mass spectral fragmentation
differentiation of 2- or 3-isopropylthio, phenylthiosuccinic acid 4
methyl/isopropyl ethers.
AB - 2- and 3-isopropylthio/phenylthiosuccinic acid 4-methyl/isopropyl esters were
synthesized regioselectively by Michael additions of isopropylthiol/thiophenol to
maleic anhydride, followed by alcoholysis with methanol/isopropanol. Their mass
spectrometric behavior has been studied with the aid of mass-analyzed ion kinetic
energy spectrometry and accurate mass measurements under electron impact
ionization. All compounds show a tendency to eliminate an alkoxy group, an
alcohol, or an alkoxycarbonyl group from the respective molecular ion. Some
molecular ions also show a tendency to eliminate a molecule of water, propene or
CO(2). The [M - MeCH = CH(2)](+) ions could further lose H(2)O to form
substituted succinic anhydride ions, or lose CO(2) to form 3-substituted
propionic acid ions. Both of these ions could further yield other small fragment
ions by loss of CO(2)H, CO or other small fragments. It has been found that 2
isopropylthio- and 3-phenylthiosuccinic acid 4-esters show more abundant [M -
H(2)O](+) peaks than their 3-isopropylthio and 2-phenylthio isomers in their mass
spectra.
PMID- 11006582
TI - A new method for the accurate determination of the isotopic state of single amide
hydrogens within peptides using Fourier transform ion cyclotron resonance mass
spectrometry.
AB - A new method is presented to accurately determine the probability of having a
deuterium or hydrogen atom on a specific amide position within a peptide after
deuterium/hydrogen (D/H) exchange in solution. Amide hydrogen exchange has been
proven to be a sensitive probe for studying protein structures and structural
dynamics. At the same time, mass spectrometry in combination with physical
fragmentation methods is commonly used to sequence proteins based on an amino
acid residue specific mass analysis. In the present study it is demonstrated that
the isotopic patterns of a series of peptide fragment ions obtained with
capillary-skimmer dissociation, as observed with a 9.4 T Fourier transform ion
cyclotron resonance (FTICR) mass spectrometer, can be used to calculate the
isotopic state of specific amide hydrogens. This calculation is based on the
experimentally observed isotopic patterns of two consecutive fragments and on the
isotopic binomial distributions of the atoms in the residue constituting the
difference between these two consecutive fragments. The applicability of the
method is demonstrated by following the sequence-specific D/H exchange rate in
solution of single amide hydrogens within some peptides.
PMID- 11006583
TI - The need for chromatographic and mass resolution in liquid chromatography/tandem
mass spectrometric methods used for quantitation of lactones and corresponding
hydroxy acids in biological samples.
AB - Because of the potential in-source conversion between a lactone and the
corresponding hydroxy acid, it has been recognized that a liquid
chromatography/tandem mass spectrometric (LC/MS/MS) method developed for
quantitation of a lactone drug in the presence of its hydroxy acid metabolite (or
vice versa) must incorporate chromatographic separation between the two
compounds, unless in-source conversion between the two compounds has been
eliminated by the appropriate selection of the LC/MS/MS parameters. We now report
that chromatographic separation between a lactone and its hydroxy acid will be
required under certain LC/MS/MS conditions used even in the absence of in-source
conversion. This is due to the fact that the 18-mass-unit difference between a
lactone and its hydroxy acid is, by coincidence, different by only one mass unit
from the 17-mass-unit difference between the [M + H](+) and [M + NH(4)](+) ions
of the lactone or the hydroxy acid. Thus, the [M + H](+) ion of a hydroxy acid is
higher than the [M + NH(4)](+) ion of its lactone by only one mass unit.
Therefore, in a method developed for quantitation of a hydroxy acid drug
utilizing a selected-ion-monitoring (SRM) scheme that incorporates its [M + H](+)
ion as the precursor ion, the quantitation would be inaccurate due to the
interference by the contribution of the A + 1 isotope response from the [M +
NH(4)](+) ion of the lactone metabolite present in the sample, unless there is a
chromatographic separation between the two compounds. This is true even if Q1 is
operated under a unit-mass resolution. The implication of this type of
interference, arising from the presence of both the [M + H](+) and [M + NH(4)](+)
ions of a drug and its metabolite, to the selection of LC and MS conditions
(including mass resolution) will be discussed using the data obtained with a
model lactone drug and its hydroxy acid metabolite.
PMID- 11006584
TI - Pyrolysis-gas chromatography/mass spectrometry of a coal extract and its
fractions separated by planar chromatography: correlation of structural features
with molecular mass
AB - The structural characterisation of a coal liquefaction extract and its three
fractions separated by planar chromatography has been described. Size exclusion
chromatography showed the molecular mass distributions to become progressively
larger with decreasing mobility on the plate. UV-fluorescence spectroscopy of the
fractions indicated parallel increases in the sizes of polynuclear aromatic ring
systems. Analysis by probe-mass spectrometry of the 'whole' coal extract showed
the expected array of small polynuclear aromatic groups extending to m/z 450. The
probe mass spectra of the lightest fraction ('mobile in pyridine and
acetonitrile') showed similar features, except for effects due to vacuum drying
to remove solvent. In sharp contrast, the two heaviest fractions ('mobile in
pyridine and immobile in acetonitrile' and 'immobile in pyridine') showed no
significant ions other than those from residual NMP solvent (m/z 98 and 99).
Pyrolysis-gas chromatography/mass spectrometry of these two heaviest fractions
showed only traces of aromatic compounds or fragments. The aromatic pyrolysis
products of these fractions were too large and involatile to pass through the GC
column. The major components observed in the pyrolysis-gas chromatography/mass
spectrometry of the two heavy fractions were alkanes and alkenes, ranging between
C10-C25. Since none of the samples contained free alkanes, alkenes or
cycloalkanes before pyrolysis, they were generated during the pyrolysis step. The
shifts of UV-fluorescence spectral intensity to shorter wavelengths with
decreasing size indicated by size exclusion chromatography (SEC) provide direct
evidence of differences in structure with changing molecular mass. This evidence
strongly suggests that species identified as being of large molecular mass in
this extract sample are not composed of molecular aggregates. It remains
difficult to establish whether and when it would be legitimate to invoke
molecular aggregates to explain the large molecular masses (MMs) identified here
and in other work. Copyright 2000 John Wiley & Sons, Ltd.
PMID- 11006585
TI - Mass spectra of new substituted 2-amino-4H-pyrans: a retro-Diels-Alder reaction
pattern.
AB - New substituted 2-amino-3-cyano-4H-pyrans have been studied by electron
ionization (EI), chemical ionization (CI) and electrospray ionization (ESI) mass
spectrometry. The retro-Diels-Alder reaction (RDA) is the main fragmentation
pattern observed in the EI spectra forming an unsaturated ketone as the diene
fragment. In contrast, a different RDA reaction takes place yielding an
unsaturated amide as diene fragment together with the unsaturated ketone in the
CI spectra. The MS/MS spectra obtained using an ESI source reveal that the
favoured fragmentation by collision induced dissociation (CID) is the elimination
of the substituent at the C4 position with formation of a stable pyrilium cation.
PMID- 11006586
TI - Evaluation of automated single mass spectrometry to tandem mass spectrometry
function switching for comprehensive drug profiling analysis using a quadrupole
time-of-flight mass spectrometer.
AB - A liquid chromatographic mass spectrometric strategy for systematic toxicological
analysis (STA) is presented using the automatic 'on-the-fly' single mass
spectrometry mode to tandem mass spectrometry mode (MS to MS/MS) switching
abilities of a quadrupole time-of-flight (Q-TOF) instrument. During the
chromatographic run, the quadrupole is initially set to transmit all masses until
(an) ion(s) reaches a certain set threshold. Thereupon, the quadrupole
automatically switches to the MS/MS mode, selecting the ion(s), which are
subsequently fragmented in the high-efficiency hexapole collision cell, thus
generating product ions that are further mass analyzed by the TOF. By limiting
the TOF spectral accumulation time in the MS/MS mode to a statistically
acceptable minimum, the quadrupole almost instantly switches back to the MS mode.
Qualitative information, comprising the complementary MS ([M + H](+) ion mass)
and MS/MS (informative product ion profile) data, as well as quantitative
information obtained by integration of the MS extracted ion chromatogram(s), can
be obtained in one single acquisition. Optimization of the automatic switching
parameters, such as threshold, TOF spectral accumulation time, detection window
and collision energy, was carried out by injection of a mix of 17 common drugs
which were not necessarily baseline separated in the chromatographic system used.
Indeed, the complete separation of the drugs is not deemed necessary since up to
8 different ions can 'simultaneously' be selected for MS/MS if they reach the
preset criteria. In addition, the quantitative performance of the method was
defined. In a second phase, the developed method was field-tested. To that end,
the resulting data from extracts of urine samples were compared with and found to
be in close concordance with those obtained by a standard toxicological analysis.
This innovative approach clearly holds the potential for a substantial advance in
the introduction of LC/MS in STA.
PMID- 11006587
TI - Electron capture dissociation of singly and multiply phosphorylated peptides.
AB - Analysis of phosphotyrosine and phosphoserine containing peptides by nano
electrospray Fourier transform ion cyclotron resonance (FTICR) mass spectrometry
established electron capture dissociation (ECD) as a viable method for
phosphopeptide sequencing. In general, ECD spectra of synthetic and native
phosphopeptides appeared less complex than conventional collision activated
dissociation (CAD) mass spectra of these species. ECD of multiply protonated
phosphopeptide ions generated mainly c- and z(.)-type peptide fragment ion
series. No loss of water, phosphate groups or phosphoric acid from intact
phosphopeptide ions nor from the c and z(.) fragment ion products was observed in
the ECD spectra. ECD enabled complete or near-complete amino acid sequencing of
phosphopeptides for the assignment of up to four phosphorylation sites in
peptides in the mass range 1400 to 3500 Da. Nano-scale Fe(III)-affinity
chromatography combined with nano-electrospray FTMS/ECD facilitated
phosphopeptide analysis and amino acid sequencing from crude proteolytic peptide
mixtures.
PMID- 11006588
TI - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of
oligosaccharides derivatized by reductive amination and N,N-dimethylation.
AB - Oligosaccharides were derivatized by reductive amination with benzylamine
followed by N,N-dimethylation with methyl iodide and analyzed by matrix-assisted
laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and
MALDI post-source decay (PSD) TOFMS. The resulting derivatives have a positive
charge localized to the modified reducing end. The derivatization methodology was
tested on maltoheptaose and three different human milk oligosaccharides. The
approximate detection limit for the resulting carbohydrate derivatives was
determined to be 50 fmol of the derivative loaded onto the target, corresponding
to a tenfold increase in sensitivity compared with underivatized
oligosaccharides. When the derivatives were analyzed by MALDI-PSD TOFMS the
observed fragmentation pattern was dominated by fragment ions retaining the
modified reducing terminus, thus simplifying the interpretation of the mass
spectral data.
PMID- 11006589
TI - Characterization of mesogen-jacketed liquid crystalline polymers by matrix
assisted laser desorption/ionization time-of-flight mass spectrometry
AB - For synthetic polymers, a proper sample preparation method is essential for
successful characterization by matrix-assisted laser desorption/ionization time
of-flight (MALDI-TOF) mass spectrometry. In this work, six synthetic mesogen
jacketed liquid crystalline polymers (MJLCPs) with different main-chain, spacer
and mesogenic units were investigated by MALDI-TOF mass spectrometry. Several
factors that affect the analysis of these polymers were examined. These factors
include matrices used, cationization salts used, the concentration of polymers,
and the ratio of sample to matrix. After testing different conditions, we found a
suitable sample preparation method for these six polymers. The number average
molecular weight (M(n)), weight average molecular weight (M(w)) and
polydispersity (PD) were calculated using data obtained in the linear mode. The
end groups of the polymers were proposed using data obtained in reflectron mode.
Copyright 2000 John Wiley & Sons, Ltd.
PMID- 11006590
TI - Electrospray ionization mass spectra of amino acid phosphoramidates of adenosine.
AB - Amino acid phosphoramidates of adenosine were synthesized and determined by
positive and negative ion electrospray ionization mass spectrometry (ESI-MS) in
conjunction with tandem mass spectrometry (MS/MS). The fragmentation pathways
were investigated. In the positive ion mass spectra abundant characteristic
fragment ions appeared, and many complementary ions were found. In the negative
ion mass spectra only a few fragment ions were observed, and most of them
contained phosphoryl groups. The results show that ESI-MS is a useful tool for
structural determination of amino acid phosphoramidates of nucleosides.
PMID- 11006591
TI - Application of matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry to insoluble glucose oligomers in decomposed cellulose.
AB - An analytical approach is described for the molecular weight characterization of
glucose oligomers from cellulose which had been decomposed by hot-compressed
water (HCW). Microcrystalline cellulose was decomposed to 18% of water insoluble
fraction (WI) plus 82% of water soluble fraction (WS) by HCW (295 degrees C, 10
mL/min). The glucose oligomers in the WI were analyzed by pericullar anion
exchange chromatography, and oligomers longer than pentamers were detected. These
results were also confirmed by matrix-assisted laser desorption/ionization time
of-flight mass spectrometry (MALDI-TOFMS). Many peaks derived from glucose
oligomers with molecular weights less than 4000 Da were detected in the spectra.
Mass differences between peaks were 162 Da, as expected for polymers composed of
glucose units. This appears to be the first report concerning molecular weight
determination of water or organic solvent insoluble compounds like glucose
oligomers from cellulose using MALDI-TOFMS.
PMID- 11006592
TI - Advantages of using nested collision induced dissociation/post-source decay with
matrix-assisted laser desorption/ionization time-of-flight mass spectrometry:
sequencing of novel peptides from wasp venom.
AB - We have examined the applicability of the 'nested' collision induced
dissociation/post-source decay (CID/PSD) method to the sequencing of novel
peptides from solitary wasps which have neurotoxic venom for paralyzing other
insects. The CID/PSD spectrum of a ladder peptide derived from an exopeptidase
digest was compared with that of the intact peptide. The mass peaks observed only
in the CID/PSD spectrum of a ladder peptide were extracted as C-terminal fragment
ions. Assignment of C-terminal fragment ions enabled calculation of N-terminal
fragment masses, leading to differentiation between N-terminal fragment ions and
internal fragment ions. This methodology allowed rapid and sensitive
identification by removing ambiguity in the assignment of the fragment ions, and
proved useful for sequencing unknown peptides, in particular those available as
natural products with a limited supply.
PMID- 11006593
TI - Measurement of 19-nortestosterone and its esters in equine plasma by high
performance liquid chromatography with tandem mass spectrometry.
AB - A high-performance liquid chromatographic-tandem mass spectrometric (HPLC/MS/MS)
method for the determination of 19-nortestosterone and its esters
(cyclopentanepropionate, phenylpropionate, and decanoate) in equine plasma is
achieved using an atmospheric pressure chemical ionization (APCI) interface in
selected reaction monitoring (SRM) mode. The two internal standards used were
16,16, 17-(2)H(3)-19-nortestosterone for 19-nortestosterone and methenolone
acetate for its esters. The steroids studied were extracted from plasma samples
with a mixture of diethyl ether/n-hexane (9:1, v/v). The quantification limits
for 19-nortestosterone, 19-nortestosterone cyclopentanepropionate, 19
nortestosterone phenylpropionate, and 19-nortestosterone decanoate were 0.16,
5.0, 0.1, and 2.0 ng/mL, respectively, when 2 mL of plasma were used. The
recoveries of most of the steroids were 71.6-101.0% except for the decanoate,
which could be recovered to about 39.8%. The responses were linear, with
correlation coefficients varying from 0.9897 to 0.9999 in the concentration range
of 0.1 to 50.0 ng/mL for the steroids studied. When applied to equine (mare)
plasma samples, the present method allowed detection of 19-nortestosterone up to
23 days after an intra-muscular injection of 400 mg as the decanoate.
PMID- 11006594
TI - Effect of sample preparation methods on the analysis of dispersed polysaccharides
by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB - Effect of sample preparation methods on the matrix-assisted laser
desorption/ionization (MALDI) analysis of dispersed polysaccharides is reported.
By using the conventional drop-drying method, the measured number-averaged
molecular weights were found to differ significantly from the values obtained
from gel-permeation chromatography (GPC). These discrepancies were found to
increase as the average masses of the polysaccharides increased. To understand
the impact of the sample preparation method on the MALDI measurement, a dispersed
dextran sample was separated into ten narrow-distribution fractions. Mixtures of
different mass fractions were prepared and analyzed by using different mixing and
preparation methods. By using the ratio of the signal intensity for the low-mass
fraction to that of the high-mass fraction as an indicator, the impact of sample
preparation conditions on the enhancement of low-mass components (or suppression
of high-mass components) was determined. From the results obtained, it is
postulated that the difference in solubilities between the low-mass and high-mass
components for dispersed polymers might be large enough to induce an enhancement
of low-mass components (or suppression of high-mass components) at the surface of
the crystals during sample crystallization in the drop-drying method.
PMID- 11006595
TI - A liquid chromatography tandem mass spectrometric method for in vivo dose
monitoring of diepoxybutane, a metabolite of butadiene.
AB - 1,3-Butadiene, a common air pollutant formed in the combustion of organic matter,
has been assessed by the U.S. EPA to be a strongly carcinogenic compound. This
risk assessment is very uncertain because of the lack of information on the dose
of the powerful carcinogenic metabolite diepoxybutane (DEB). This report presents
an analytical method for in vivo dose monitoring of a unique marker for DEB. For
a large number of alkylating agents in vivo doses are monitored by measurement by
gas chromatography/mass spectrometry (GC/MS) of adducts to N-terminal valine in
hemoglobin (Hb), using a modified Edman degradation method. This method is
applicable to monofunctional epoxides from butadiene. However, in reaction with N
terminal valine, DEB forms an adduct which is ring-closed to a pyrrolidine, N,N
(2,3-dihydroxy-1,4-butadiyl)valine, with a tertiary amino group that prevents
detachment of the alkylated valine by the Edman reagent. Therefore a method has
been developed based on the analysis by liquid chromatography/electrospray
ionization mass spectrometry (LC/ESI-MS) of the N-modified N-terminal peptides
enriched after trypsin digestion of globin. In this study Hb samples from mice
injected intraperitoneally with (+/-)-DEB were examined qualitatively and
quantitatively with regard to the ring-closed adduct. The N-terminal pyrrolidine
heptapeptide was identified in treated mice. The highest adduct levels were
obtained in samples from animals given the highest dose of DEB and the adduct
levels were below the detection level in control mice.
PMID- 11006596
TI - Using a superconducting tunnel junction detector to measure the secondary
electron emission efficiency for a microchannel plate detector bombarded by large
molecular ions
AB - An energy-sensitive superconducting tunnel junction (STJ) detector was used to
measure the secondary electron emission efficiency, epsilon(e), for a
microchannel plate (MCP) detector bombarded by large (up to 66 kDa), slow moving
(<40 km/s) molecular ions. The method used is new and provides a more direct
procedure for measuring the efficiency of secondary electron emission from a
surface. Both detectors were exposed simultaneously to nearly identical ion
fluxes. By exposing only a small area of the MCP detector to ions, such that the
area exposed was effectively the same as the size of the STJ detector, the number
of ions detected with each detector were directly comparable. The STJ detector is
100% efficient for detecting ions in the energy regime investigated and therefore
it can be used to measure the detection efficiency and secondary electron
emission efficiency of the MCP. The results are consistent with measurements made
by other groups and provide further characterization of the loss in sensitivity
noted previously when MCP detectors have been used to detect high-mass ions.
Individual molecular ions of mass 66 kDa with 30 keV kinetic energy were measured
to have about a 5% probability of producing one or more electrons when impacting
the MCP. When ion energy was reduced to 10 keV, the detection probability
decreased to 1 %. The secondary electron yield was calculated from the secondary
electron emission efficiency and found to scale linearly with the mass of the
impinging molecular ion and to about the fourth power of ion velocity. Secondary
electrons were observed for primary ion impacts >5 km/s, regardless of mass, and
no evidence of a velocity (detection) threshold was observed. Copyright 2000 John
Wiley & Sons, Ltd.
PMID- 11006597
TI - Effects of ultraviolet irradiation on melanogenesis from tyrosine, Dopa and
dopamine: a matrix-assisted laser desorption/ionization mass spectrometric study.
AB - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry experiments
were applied to study the influence of ultraviolet (UV) irradiation in
melanogenesis. Samples were prepared starting from three different precursors,
tyrosine, Dopa and dopamine, in the presence or absence of tyrosinase, the enzyme
responsible for the synthesis of melanin. Enzymatic reactions were carried out
for 10, 30, 60 and 120 min under UV irradiation at 365 nm, and aliquots were then
immediately ultrafiltered and lyophilized. Samples obtained by irradiation of
tyrosine solution revealed the formation of 5,6-dihydroxyindole (DHI) oligomers
up to pentamers at 120 min; the reaction kinetics were markedly enhanced in the
presence of tyrosinase. In the case of Dopa, UV irradiation favored melanogenesis
only in the presence of the enzyme; in this case, many reaction pathways were
activated, originating various oligomeric species of Dopa, DHI and 5,6
dihydroxyindole-2-carboxylic acid (DHICA). Conversely, when dopamine was used as
tyrosinase substrate under UV light, mechanisms of melanogenesis different from
those generated by simple enzymatic reaction without irradiation were not
activated, as the same oligomeric species were present.
PMID- 11006598
TI - Characterization of zirconium complexes of interest in spent nuclear fuel
reprocessing by electrospray ionization mass spectrometry
AB - Liquid-liquid extraction of zirconium, one of the most important fission
products, was followed using electrospray ionization mass spectrometry under
conditions simulating reprocessing of nuclear spent fuel. Zr(IV) can precipitate
from the organic phase after extraction by dibutylphosphoric acid (HDBP), the
most common degradation product of tributylphosphate (TBP) radiolysis. Different
complexes were detected with electrospray used in positive or negative ion modes,
according to the extraction conditions such as the ligand/metal ratio.
Stoichiometry of the Zr(IV) complexes was determined by combining isotopic
labeling [H(15)NO(3)] of the aqueous phase in the extraction system and tandem
mass spectrometry experiments. These results were compared with the species
observed using other techniques reported in the literature. The mechanisms of
ionization/desorption of these complexes are proposed depending on the organic
ligand character (neutral (L) such as TBP, or acidic (HL') such as HDBP), and the
ionization mode used. Copyright 2000 John Wiley & Sons, Ltd.
PMID- 11006599
TI - Oxygen attachment to metal complex ions during their collision induced
dissociation in ion trap
PMID- 11006600
TI - Editorial
PMID- 11006601
TI - Tandem mass spectrometry: dissociation of ions by collisional activation
AB - This review presents a brief historical introduction to the development of tandem
mass spectrometry and its principal applications. It is placed in the context of
the general principles underlying mass spectrometry, particularly the
relationships between internal energy and fragmentation kinetics. The center-of
mass framework is presented as a convenient means of applying conservation of
momentum to the energy transfer problem in tandem mass spectrometry as a means of
deducing energy transfer in the collisional activation step and kinetic energy
release as activated ions dissociate into fragment ions and neutrals. The
principles of molecular beam methods are summarized and illustrative examples are
given for which definitive information on reaction dynamics is available. The
importance of scattering-very little appreciated in early discussions of tandem
mass spectrometry-is shown to be the natural consequence of impulsive collisions,
which appears to be a general mechanism for energy exchange in collisional
activation. It is shown that the average energy transferred in single collisions
is much less than the theoretical maximum given by the center-of-mass collision
energy and the Massey criterion is presented as a simplistic rationale for
understanding the essentially exponential decline in the energy transfer function
above and below the relative velocity at which the probability for energy
transfer is maximized. The issues of energy transfer in collisions of large
molecular ions with low-mass neutrals are reviewed and a general description of
energy transfer in multiple collisions is presented. It is shown that the center
of-mass and Massey criterion limitations are pragmatically overcome by multiple
collision activation in ion traps. Surface-induced dissociation is presented as a
viable alternative to multiple collision activation which is especially
attractive for activation of large molecular ions. Finally, a few of the emerging
dynamics principles governing energy transfer and dissociation of peptides are
summarized. Copyright 2000 John Wiley & Sons, Ltd.
PMID- 11006602
TI - Determination of phenothiazines in human body fluids by solid-phase
microextraction and liquid chromatography/tandem mass spectrometry.
AB - Eleven phenothiazine derivatives with heavy side-chains were found to be
extractable from human whole blood and urine samples by solid-phase
microextraction (SPME) with a polyacrylate-coated fiber. The fiber was then
injected into the desorption chamber of an SPME-liquid chromatography (LC)
interface for LC/tandem mass spectrometry (MS/MS) with positive ion electrospray
(ES) ionization. All compounds formed base peaks due to [M + 1](+) ions by LC/ES
MS/MS. By use of LC/ES-MS/MS, the product ions produced from each [M + 1](+) ion
showed base peaks due to side-chain liberation. Selected reaction monitoring
(SRM) and selected ion monitoring (SIM) were compared for the detection of the 11
phenothiazine derivatives from human whole blood and urine. SRM showed much
higher sensitivity than SIM for both types of sample. Therefore, a detailed
procedure for the detection of drugs by SRM with SPME-LC/MS/MS was established
and carefully validated. The extraction efficiencies of the 11 phenothiazine
derivatives spiked into whole blood and urine were 0. 0002-0.12 and 2.6-39.8%,
respectively. The regression equations for the 11 phenothiazine derivatives
showed excellent linearity with detection limits of 0.2-200 ng ml(-1) for whole
blood and 4-22 pg ml(-1) for urine. The intra- and inter-day precisions for whole
blood and urine samples were not greater than 15.1%. The data obtained after oral
administration of perazine or flupentixol to a male subject are presented.
PMID- 11006603
TI - Negative ion chemical ionization for the determination of methylphenidate in
human plasma by stable isotope dilution gas chromatography/mass spectrometry.
AB - A sensitive and specific method for the determination of methylphenidate in human
plasma is presented. Methylphenidate was extracted from plasma by solvent
extraction with hexane at pH 9.3 and derivatized to its heptafluorobutyrate
derivative. The derivative was measured by gas chromatography/negative ion
chemical ionization mass spectrometry without any further purification. Using
this detection mode, a diagnostically useful fragment ion at m/z 369 was obtained
at high relative abundance. (18)O(2)-labelled methylphenidate was used as an
internal standard and its rapid and facile preparation from the unlabeled
compound is described. Calibration graphs were linear within the range 0.14-18.25
ng ml(-1). The inter-assay precision was 8.7% (0.14 ng ml(-1)) and 3.1% (4.56 ng
ml(-1)) and the intra-assay variability was 1.3% (0.14 ng ml(-1)) and 0.4% (4.56
ng ml(-1)). Accuracy determinations showed deviations of +0.7% (0.14 ng ml(-1))
and -2.5% (4.56 ng ml(-1)). The method is rugged, rapid and robust and has been
applied to the batch analysis of methylphenidate during pharmacokinetic profiling
of the drug.
PMID- 11006604
TI - Comparison of a jet separator and an open splitter as an interface between a
multi-capillary gas chromatographic column and a time-of-flight mass spectrometer
AB - A gas chromatographic/time-of-flight mass spectrometric (GC/TOFMS) interface is
being developed for fast on-line analysis utilizing multi-capillary column
technology. A variable gap-distance jet separator has been constructed and its
performance compared with that of a commercially supplied post-column open
splitter recommended for use between the multi-capillary column and a mass
spectrometer. Both interfaces were found to be compatible with the GC/TOFMS
system at high carrier gas flow-rates, facilitating high-speed and high
resolution separations. The systems were investigated and tested with a mixture
of volatile organic compounds (VOCs) with molecular masses from 85 to 166:
dichloromethane, toluene, m-dichlorobenzene, o-dichlorobenzene and
tetrachloroethylene. The optimum tip-to-tip gap distance corresponding to the
highest efficiency of the jet separator was found to be 0.030 mm for each
compound at carrier gas flow-rates of 20, 40 and 60 ml min(-1) giving, in the ion
source housing, ion gauge pressure readings of 1.6 x 10(-6), 5.0 x 10(-6) and 5.8
x 10(-6) mbar, respectively. The efficiency of the jet separator (10-30% yields)
was significantly higher than that of the open splitter (6-9% yields). The
observation that the open splitter did not provide a constant flow-rate to the
ion source was not in agreement with the manufacturer's specifications. A method
for measuring the gas flow-rates in all parts of the equipment is described. The
correlation between yield in the jet separator and molecular mass for the
heterogeneous set of compounds studied was found to be less linear than usually
reported for homologous series of compounds in jet separator studies. The result
suggests that the pressure conditions in the jet may be sufficient for the
separation process to be partly controlled by diffusion rather than predominately
by effusion. Copyright 2000 John Wiley & Sons, Ltd.
PMID- 11006606
TI - Characterization of isopoly metal oxyanions using electrospray time-of-flight
mass spectrometry
AB - Electrospray time-of-flight mass spectrometry was used to study dilute (10(-3) M)
solutions of tungstate, vanadate and perrhenate oxyanions under acidic and basic
conditions. The electrospray mass spectra of tungstate and vanadate solutions
indicate the presence of protonated monomeric oxyanions in basic solution (pH
approximately 10) and protonated polymeric species in acidic solutions (pH
approximately 4). Monomeric perrhenate was the only species detected in both
acidic and basic perrhenate solutions. For all three systems, the core metalate
species detected by electrospray were consistent with reported speciation in
aqueous solutions. Copyright 2000 John Wiley & Sons, Ltd.
PMID- 11006605
TI - Isolation from rat urine and human liver microsomes and identification by
electrospray and nanospray tandem mass spectrometry of new malagashanine
metabolites.
AB - Malagashanine has been isolated from indigenous madagascan Strychnos myrtoides
alkaloids used traditionally to treat malaria. This alkaloid was found to enhance
the action of chloroquine against chloroquine-resistant strains of Plasmodium
falciparum when combined with classical antimalarial drugs (chloroquine,
quinine). The present study was carried out in order to investigate by
electrospray mass and tandem mass spectrometry and NMR spectroscopy the structure
of two new metabolites isolated from rat urine and human liver microsomes. We
were able to demonstrate the presence of two new metabolites of malagashanine
corresponding to a malagashanine N-demethylated metabolite and to the oxidation
of malagashanine in the alpha-position of the N-methyl group to produce a
carbinolamine function. The latter metabolite may be subject to ring and open
chain tautomerism effects and dimeric species were detected in the electrospray
mass spectrum.
PMID- 11006607
TI - Use of an automated chromium reduction system for hydrogen isotope ratio analysis
of physiological fluids applied to doubly labeled water analysis.
AB - The doubly labeled water method is commonly used to measure total energy
expenditure in free-living subjects. The method, however, requires accurate and
precise deuterium abundance determinations, which can be laborious. The aim of
this study was to evaluate a fully automated, high-throughput, chromium reduction
technique for the measurement of deuterium abundances in physiological fluids.
The chromium technique was compared with an off-line zinc bomb reduction
technique and also subjected to test-retest analysis. Analysis of international
water standards demonstrated that the chromium technique was accurate and had a
within-day precision of <1 per thousand. Addition of organic matter to water
samples demonstrated that the technique was sensitive to interference at levels
between 2 and 5 g l(-1). Physiological samples could be analyzed without this
interference, plasma by 10000 Da exclusion filtration, saliva by sedimentation
and urine by decolorizing with carbon black. Chromium reduction of urine
specimens from doubly labeled water studies indicated no bias relative to zinc
reduction with a mean difference in calculated energy expenditure of -0.2 +/-
3.9%. Blinded reanalysis of urine specimens from a second doubly labeled water
study demonstrated a test-retest coefficient of variation of 4%. The chromium
reduction method was found to be a rapid, accurate and precise method for the
analysis of urine specimens from doubly labeled water.
PMID- 11006609
TI - Collision-induced dissociation spectra versus collision energy (collision-induced
dissociation curve) using a quadrupole ion trap mass spectrometer. II.(1) loss of
CO from ionized o-, m- and p-anisoyl fluoride, CH(3)OC(6)H(4)COF(+.)
PMID- 11006608
TI - Quantitation of simvastatin and its beta-hydroxy acid in human plasma by liquid
liquid cartridge extraction and liquid chromatography/tandem mass spectrometry.
AB - A sensitive and reliable procedure for the simultaneous determination of
simvastatin (SV) and its active beta-hydroxy acid metabolite (SVA) in human
plasma was developed and validated. The analytes were extracted simultaneously
from 0.5 ml aliquots of human plasma samples by methyl tert-butyl ether (MTBE)
via Chem Elut cartridge extraction [also called liquid-solid extraction (LSE) or
liquid-liquid cartridge extraction (LLCE)], separated through a Kromasil C(18)
column (50 x 2 mm i.d. 5 microm) and detected by tandem mass spectrometry with a
turbo ionspray interface. Stable isotope-labeled SV and SVA, (13)CD(3)-SV and
(13)CD(3)-SVA, were used as internal standards. SV and SVA were detected in
positive and negative ion modes, respectively, via within-run polarity switching.
The use of Chem Elut cartridges not only provided a simple and efficient means of
plasma sample extraction but also successfully reduced the interconversion
between SV and SVA to an undetectable (for lactonization of SVA) or negligible
(<0.07%, for hydrolysis of SV) level. The method showed excellent
reproducibility, with intra- and inter-assay precisions <4.5% (RSD), and intra-
and inter-assay accuracy between 94% and 107% of nominal values, for both
analytes. The extraction recoveries were 78% and 87% on average for SV and SVA,
respectively. The analyte was found to be stable in plasma through three freeze (
70 degrees C)-thaw (4 degrees C) cycles and for at least 3 h under bench-top
storage condition in an ice-bath (4 degrees C), and also in the reconstitution
solution at 4 degrees C for at least 24 h. The method has a lower limit of
quantitation (LOQ) of 50 pg ml(-1) with a linear calibration range of 0.05-50 ng
ml(-1) for both analytes, and has proved to be very reliable for the analysis of
clinical samples.
PMID- 11006610
TI - Current literature in mass spectrometry.
AB - In order to keep subscribers up-to-date with the latest developments in their
field, John Wiley & Sons are providing a current awareness service in each issue
of the journal. The bibliography contains newly published material in the field
of mass spectrometry. Each bibliography is divided into 11 sections: 1 Books,
Reviews & Symposia; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion
Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins;
Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural
Products; 7 Analysis of Organic Compounds; 8 Analysis of
Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11
Elemental Analysis. Within each section, articles are listed in alphabetical
order with respect to author (3 Weeks journals - Search completed at 28th. June
2000)
PMID- 11006611
TI - Prion diseases.
PMID- 11006612
TI - Future employment of allopathic medical graduates.
PMID- 11006613
TI - Doctor-population ratios.
PMID- 11006614
TI - Thalassaemia control in developing countries--the Sri Lankan perspective.
AB - Beta thalassaemia is a Mendelian recessive disorder. The economic and social cost
of the disease is high due to patients' life long need for monthly blood
transfusions and treatment with desferrioxamine, an iron chelating agent. Wider
availability of cheaper drugs is on the horizon. If there is no concomitant
reduction in the number of new thalassaemia major births, there will be a
cumulative increase in numbers requiring treatment. The frequency and severity,
and the economic and social costs of thalassaemia, support the case for the
introduction of a carrier screening and counselling program in Sri Lanka. A three
pronged plan emphasising professional, political and public education in
outlined.
PMID- 11006615
TI - Suicide in Sri Lanka: points to ponder.
PMID- 11006616
TI - Suicide: a Socratic revenge.
AB - 2400 years have passed since the occurrence in Athens, Greece of one of the
famous suicides recorded in human history. This autobiographical essay provides a
montage on the history of suicide, with snippets from the final hours of
Socrates, as described by Plato. Suicide in contemporary Japanese culture is also
explored briefly, with reference to the deaths of internationally acclaimed movie
directors Akira Kurosawa and Juzo Itami. The author also questions why no
researcher has yet been honoured for the past 99 years with a Medicine Nobel
prize for his or her work on suicidology or thanatology.
PMID- 11006617
TI - Paradoxical progression of intracranial tuberculous lesions during treatment.
PMID- 11006618
TI - A case of hereditary sensory and autonomic neuropathy (HSAN) type II.
AB - We describe a case of hereditary sensory and autonomic neuropathy (HSAN) type II
in a child with a penetrating foot ulcer, acral sensory impairment, and
anhidrosis. This is the first documentation of HSAN in Sri Lanka.
PMID- 11006619
TI - Mixed medullary follicular carcinoma--an unusual thyroid neoplasm.
PMID- 11006620
TI - Acute primary axonal Guillain-Barre syndrome.
PMID- 11006621
TI - Sleeping sickness and teaching of medical students.
PMID- 11006622
TI - Sleeping sickness in Sri Lanka.
PMID- 11006623
TI - Sleeping sickness in Sri Lanka.
PMID- 11006624
TI - Inhaled steroids for childhood asthma.
PMID- 11006625
TI - Metformin in diabetes mellitus: are we choosing the right patients?
PMID- 11006626
TI - Heat stroke in young adults: in reply.
PMID- 11006627
TI - A cautionary tale: intra-amniotic injection of methylene blue.
PMID- 11006628
TI - Impact of new diagnostic criteria for diabetes on its prevalence in a hospital
population.
PMID- 11006629
TI - The Neurospora am gene and NADP-specific glutamate dehydrogenase: mutational
sequence changes and functional effects--more mutants and a summary.
AB - A further series of mutant am alleles, encoding potentially active NADP-specific
glutamate dehydrogenase (GDH) and capable of complementation in heterocaryons,
have been characterized with respect to both GDH properties and DNA sequence
changes. Several mutants previously studied, and some of their same-site or
second-site revertants, have also been sequenced for the first time. We present a
summary of what is known of the properties of all am mutants that have been
defined at the sequence level.
PMID- 11006630
TI - Temperature-induced alteration of the polytene X chromosome structure in male
larvae of the strain In(1)BM2 (reinverted) of Drosophila melanogaster.
AB - In Drosophila melanogaster, the polytene X chromosome of male third instar larva
appears twice as wide as an unpaired female X chromosome or an autosome. This
characteristic morphology of the male X chromosome is correlated with the
increased rate of transcription of the sex-linked genes, which ensures gene
dosage compensation. In male third instar larvae of the strain In(1)BM2
(reinverted), polytene nuclei manifest unusually puffy X chromosomes at 18 +/- 1
degrees C. Such 'puffy X' chromosomes are pompons, that is, despite the increased
width of the chromosome, transcription remains at the wild-type level. This
characteristic is a caveat to the invariable correlation between polytene
chromosome puffs and transcription, and suggests that the mutant X chromosomes
arise due to perturbation of a pathway that controls the structure but not the
transcription of the polytene X chromosome. In this report we present evidence
that the pompons of In(1)BM2 (reinverted) arise due to spiralization of the male
X chromosome, which results in condensing of the chromosome. This unusual
structural alteration can be induced only in male larvae of this strain, at the
third instar larval stage, through temperature shifts from 24 +/- 1 degrees C to
18 +/- 1 degrees C and during recovery from cold shock. Furthermore, extract from
male adult, pupae and third instar larvae can induce chromosome condensation in
wild-type larvae in vitro. This new evidence not only explains the absence of
correlation between chromosome width and transcription of the pompons of In(1)BM2
(reinverted), but also suggests that the chromosomal rearrangement perturbs a
pathway that regulates the condensation of chromosomes.
PMID- 11006631
TI - Polymorphism of M factors in populations of the housefly, Musca domestica L., in
Turkey.
AB - M factors, which determine maleness in Musca domestica, were found on the second,
third, fourth and fifth linkage groups in housefly populations of Turkey. As in
European populations, the male-determining factor was more frequently located on
linkage group III (MIII). Some males homozygous or double heterozygous for M
factors were identified. Deviations from a 1:1 sex ratio in favour of males, as
well as mosaics for somatic marker mutations and sexual mosaics (gynandromorphs),
were also observed. The results reveal an extensive polymorphism in the sex
determining system.
PMID- 11006632
TI - Quantitative trait loci for directional but not fluctuating asymmetry of mandible
characters in mice.
AB - Non-directional variation in right minus left differences in bilateral
characters, referred to as fluctuating asymmetry (FA), often has been assumed to
be largely or entirely environmental in origin. FA increasingly has been used as
a measure of developmental stability, and its presumed environmental origin has
facilitated the comparisons of populations believed to differ in their levels of
stability. Directional asymmetry (DA), in which one side is consistently larger
than the other, has been assumed to be at least partially heritable. Both these
assumptions were tested with interval mapping techniques designed to detect any
quantitative trait loci (QTLs) affecting FA or DA in 15 bilateral mandible
characters in house mice resulting from a cross of the F1 between CAST/Ei (wild
strain) and M16i (selected for rapid growth rate) back to M16i. For purposes of
the analysis, all mandibles were triply measured and 92 microsatellite markers
were scored in a total of 350 mice. No significant QTLs were found for FA, but
three QTLs significantly affected DA in several characters, confirming both
assumptions. The QTLs for DA were similar in location to those affecting the size
of several of the mandible characters, although they accounted for an average of
only 1% of the total phenotypic variation in DA.
PMID- 11006634
TI - The effect of subdivision on variation at multi-allelic loci under balancing
selection.
AB - Simulations are used to investigate the expected pattern of variation at loci
under different forms of multi-allelic balancing selection in a finite island
model of a subdivided population. The objective is to evaluate the effect of
restricted migration among demes on the distribution of polymorphism at the
selected loci at equilibrium, and to compare the results with those expected for
a neutral locus. The results show that the expected number of alleles maintained,
and numbers of nucleotide differences between alleles, are relatively insensitive
to the migration rate, and differentiation remains low even under very restricted
migration. However, nucleotide divergence between copies of functionally
identical alleles increases sharply when migration decreases. These results are
discussed in relation to published surveys of allelic diversity in MHC and plant
self-incompatibility systems, and to the possibility of inferring ancient
population genetic events and processes. In addition, it is shown that, for
sporophytic self-incompatibility systems, it is not necessarily true in a
subdivided population that recessive alleles are more frequent than dominant
ones.
PMID- 11006633
TI - Characterization and differential expression of a human gene family of
olfactomedin-related proteins.
AB - Olfactomedin-related proteins are secreted glycoproteins with conserved C
terminal motifs. Olfactomedin was originally identified as the major component of
the mucus layer that surrounds the chemosensory dendrites of olfactory neurons.
Homologues were subsequently found also in other tissues, including the brain and
in species ranging from Caenorhabditis elegans to Homo sapiens. Most importantly,
the TIGR/myocilin protein, expressed in the eye and associated with the
pathogenesis of glaucoma, is an olfactomedin-related protein. The prevalence of
olfactomedin-related proteins among species and their identification in different
tissues prompted us to investigate whether a gene family exists within a species,
specifically Homo sapiens. A GenBank search indeed revealed an entire human gene
family of olfactomedin-related proteins with at least five members, designated
hOlfA through hOlfD and the TIGR/myocilin protein. hOlfA corresponds to the rat
neuronal AMZ protein. Phylogenetic analyses of 18 olfactomedin-related sequences
resolved four distinct subfamilies. Among the human proteins, hOlfA and hOlfC,
both expressed in brain, are most closely related. Northern blot analyses of 16
human tissues demonstrated highly specific expression patterns: hOlfA is
expressed in brain, hOlfB in pancreas and prostate, hOlfC in cerebellum, hOlfD in
colon, small intestine and prostate and TIGR/myocilin in heart and skeletal
muscle. The link between TIGR/myocilin and ocular hypertension and the expression
of several of these proteins in mucus-lined tissues suggest that they play an
important role in regulating physical properties of the extracellular
environment. Future studies can now assess whether other members of this gene
family, like TIGR/myocilin, are also associated with human disease processes.
PMID- 11006635
TI - The effect of hitch-hiking on genes linked to a balanced polymorphism in a
subdivided population.
AB - The effect of multi-allelic balancing selection on nucleotide diversity at linked
neutral sites was investigated by simulations of subdivided populations. The
motivation is to understand the behaviour of self-recognition systems such as the
MHC and plant self-incompatibility. For neutral sites, two types of subdivision
are present: (1) into demes (connected by migration), and (2) into classes
defined by different functional alleles at the selected locus (connected by
recombination). Previous theoretical studies of each type of subdivision
separately have shown that each increases diversity, and decreases the relative
frequencies of low-frequency variants, at neutral sites or loci. We show here
that the two types of subdivision act non-additively when sampling is at the
whole population level, and that subdivision produces some non-intuitive results.
For instance, in highly subdivided populations, genetic diversity at neutral
sites may decrease with tighter linkage to a selected locus or site. Another
conclusion is that, if there is population subdivision, balancing selection leads
to decreased expected FST values for neutral sites linked to the selected locus.
Finally, we show that the ability to detect balancing selection by its effects on
linked variation, using tests such as Tajima's D, is reduced when genes in a
subdivided population are sampled from the total population, rather than within
demes.
PMID- 11006636
TI - Effects of population structures and selection strategies on the purging of
inbreeding depression due to deleterious mutations.
AB - Stochastic simulations were run to compare the effects of nine breeding schemes,
using full-sib mating, on the rate of purging of inbreeding depression due to
mutations with equal deleterious effect on viability at unlinked loci in an
outbred population. A number of full-sib mating lines were initiated from a large
outbred population and maintained for 20 generations (if not extinct). Selection
against deleterious mutations was allowed to occur within lines only, between
lines or equal within and between lines, and surviving lines were either not
crossed or crossed following every one or three generations of full-sib mating.
The effectiveness of purging was indicated by the decreased number of lethal
equivalents and the increased fitness of the purged population formed from
crossing surviving lines after 20 generations under a given breeding scheme. The
results show that the effectiveness of purging, the survival of the inbred lines
and the inbreeding level attained are generally highest with between-line
selection and lowest with within-line selection. Compared with no crossing, line
crossing could lower the risk of extinction and the inbreeding coefficient of the
purged population substantially with little loss of the effectiveness of purging.
Compromising between the effectiveness of purging, and the risk of extinction and
inbreeding coefficient, the breeding scheme with equal within- and between-line
selection and crossing alternatively with full-sib mating is generally the most
desirable scheme for purging deleterious mutations. Unless most deleterious
mutations have relatively large effects on fitness in species with reproductive
ability high enough to cope with the depressed fitness and thus increased risk of
extinction with inbreeding, it is not justified to apply a breeding programme
aimed at purging inbreeding depression by inbreeding and selection to a
population of conservation concern.
PMID- 11006637
TI - Fine-mapping of quantitative trait loci in half-sib families using current
recombinations.
AB - Two groups of methods are being developed to fine-map quantitative trait loci
(QTLs): identity-by-descent methods or methods using historical recombinations,
and genetic chromosome dissection methods or methods utilizing current
recombinations. Here we propose two methods that fall into the second group:
contrast mapping and substitution mapping. A QTL has previously been detected via
linkage mapping in a half-sib design (granddaughter or daughter design), and
sires (grandsires) likely to be heterozygous at the QTL have been identified. A
sire (grandsire) and its recombinant offspring are then genotyped for a series of
ordered markers spanning the initial marker interval. Offspring are grouped by
paternal multi-marker haplotype with haplotypes differing in the location of the
recombination event. In the contrast method, contrasts between the phenotypic
averages of haplotypes or offspring groups are calculated which correspond to
marker intervals within the original interval. The expected value of the contrast
for the true QTL interval is always maximum, hence the interval with maximum
observed contrast is assumed to contain the QTL. Alternative statistics for
determining the interval most likely to contain a QTL are presented for contrast
mapping, as well as a bootstrap estimation of the probability of having
identified the correct interval. For an initial marker bracket of 20 cM and 10
additional equidistant markers, the probability of assigning the QTL to the
correct 2 cM marker interval or to a combined 4 cM interval was calculated. For
substitution effects of 0.093, 0.232, 0.464, 0.696 and 0.928 (in additive genetic
SD), power values near 0.14, 0.26, 0.48, 0.67 and 0.80 (0.25, 0.53, 0.86, 0.97
and 0.99) are achieved for a family of 200 (1000) sons, respectively. In
substitution mapping, QTL segregation status of recombinant sons must be
determined using daughter genotyping. Combinations of two haplotypes with their
segregation status are required to assign the QTL to an interval. Probabilities
of correct QTL assignment were calculated assuming absence of the mutant QTL
allele in dams of sons. For a 2 cM interval and a QTL at the midpoint of an
interval, power near 0.95 (0.90) is reached when the number of recombinant sons
is 70 (60), or total number of sons is 424 (363). For QTL positions away from the
midpoint, power decreases but can be improved by combining marker intervals. For
a QTL located halfway to the midpoint, and 182 sons in a family resulting in 30
recombinant sons, probability is 0.94 for assignment to either a 2 cM or a
combined 4 cM interval. Effect of type I and type II errors in segregation status
determination on power of QTL assignment was found to be small. Errors in
segregation status due to QTL segregation in dams have an impact if the frequency
of the mutant QTL allele is intermediate to high.
PMID- 11006638
TI - Mapping quantitative trait loci in tetraploid populations.
AB - Knowledge of quantitative trait locus (QTL) mapping in polyploids is almost void,
albeit many exquisite strategies of QTL mapping have been proposed and extensive
investigations have been carried out in diploid animals and plants. In this paper
we develop a simple algorithm which uses an iteratively reweighted least square
method to map QTLs in tetraploid populations. The method uses information from
all markers in a linkage group to infer the probability distribution of QTL
genotype under the assumption of random chromosome segregation. Unlike QTL
mapping in diploid species, here we estimate and test the compound 'gametic
effect', which consists of the composite 'genic effect' of alleles and higher
order gene interactions. The validity and efficiency of the proposed method are
investigated through simulation studies. Results show that the method can
successfully locate QTLs and separates different sources (e.g. additive and
dominance) of variance components contributed by the QTLs.
PMID- 11006639
TI - High copy numbers of multiple transposable element families in an Australian
population of Drosophila simulans.
AB - Sudden mobilization of transposable elements in Drosophila is a well-reported
phenomenon but one that usually affects no more than a few elements (one to
four). We report here the existence of a D. simulans natural population
(Canberra) from Australia, which had high copy numbers for various transposable
elements (transposons, LTR retrotransposons and non-LTR retrotransposons). The
impact of transposable elements on the host genome and populations is discussed.
PMID- 11006640
TI - [Frequency of colicin and hemolysins in Escherichia coli isolated from pregnant
patients with urinary tract infection, symptomatic and asymptomatic].
AB - Colicin production was studied among 137 Escherichia coli strains isolated from
pregnant patients with symptomatic or asymptomatic, urinary tract infection
(IVU). The observed colicinogeny frequency was 72.92% (n = 96), among the
symptomatic patients and 29.26% (n = 41) among the asymptomatic group. The most
frequently identified colicins from symptomatic patients were: V (23.9%), A
(18.7%) and E1 (17.7%) and within the patients with asymptomatic IVU the most
frequently observed colicins were A (9.7%), E1 (17.0%) y V (2.4%). The major
frequency of colicin V among the E. coli strains isolated from the symptomatic
group against the asymptomatic one, was statistical significant (p > or = 0.025).
The results on the observed frequencies of colicins E1 and A were not statistical
significant. Among the 137 studied E. coli strains, 37.2% were hemolytic. 83.3%
of the colicin V producing strains (n = 24) were hemolytic, among the strains
producing other colicin different than colicin V 34% (n = 58) were hemolytic and
12.0% of non colicinogenic strains were hemolytic. These results were statistical
significant (p > 0.05). The present data, suggest that colicins production is an
important pathogenicity factor among the E. coli strains, specially for those
strains producing colicin V. The observed association among hemolysin and colicin
V production may be an interesting pathogenicity factor which suggests an
increasing ability of uropathogenic strains to produce symptomatic urinary tract
infections.
PMID- 11006641
TI - [Non-immunologic hydrops. Report of 2 cases].
AB - Non immune hydrops is an uncommon entity, it is observed in one per 2,000 to
3,500 alive birth. It can be idiopathic or secondary to different pathologies,
the most important examples are: congenital malformations, cromosompathies or
viral infections. OBJECTIVE: To show our therapeutic and diagnostic experience in
two cases of non immune hydrops. STUDY DESIGN: To present a case of spontaneous
reversion of non immune hydrops secondary to parvovirus B 19 infection and other
case secondary to congenital cardiopathy. RESULTS: We found spontaneous reversion
of a case of non immune hydrops due to a parvovirus B 19 infection and infant was
normal but the infant with congenital cardiopathy died ten minutes after birth.
CONCLUSIONS: Two of the most important causes of non immune hydrops are
cardiopathies and infections, specially parvovirus which is responsible of poor
perinatal outcome but there is a remote possibility of spontaneous reversion
because it is important to make a specific diagnose and to make the expected
management.
PMID- 11006642
TI - [Methods of pedicle hemostasis in laparoscopically-assisted vaginal hysterectomy
(VAVH). Evaluation of results].
AB - The objective was to evaluate whether use of different techniques of hemostasia
have effect on laparoscopically assisted vaginal hysterectomy (LAVH) morbidity.
Was performed a review of 53 LAVH cases, parameters analyzed were type of
hemostasia method and surgical complications. There were five patients with
transoperative bleeding and two with incidental bladder lesion, that were managed
successfully without complications. There were no significant differences between
types of hemostasia with respect to transoperative bleeding. There were no mayor
surgical complications in the studied patients. As conclusion LAVH allows
patients a expedite recovery with low postoperative complications. All the
methods used in this work to perform hemostasia in LAVH are safe and effective
for patients with habitual hysterectomy indications.
PMID- 11006643
TI - [Prenatal corticosteroids. Use and attitudes of the gynecology-obstetrics medical
staff].
AB - OBJECTIVES: 1. To evaluate the frequency of use of antenatal corticosteroids (AC)
and the reasons for withholding them. 2. To estimate the knowledge and attitudes,
regarding AC, from obstetricians, in a large Women and Babies Hospital. METHODS:
Through a prospective, observational and transversal study we evaluated: 1. The
frequency of use of AC in pregnant with preterm labor (PL) and in mothers of
preterm infants (P1). When AC were not given, the reasons were recorded. 2. With
an anonymous inquiry we assessed the knowledge and attitude of obstetricians
regarding AC, exploring different concepts such as usefulness, frequency of use,
indications, risks and contraindications. Descriptive statistics was used.
RESULTS: We studied 364 patients (240 mothers of Pl and 124 pregnant women). The
mean gestational age (GA) was 28.9 + 2.4 weeks. The AC were used only in 136 out
of 364 (37.4%) women, and diminished to 30.9% (102/330), if are excluded 34
patients who did not receive AC because imminent delivery. Another reasons for
not using AC were irregular uterine activity (18.9%), prolonged rupture of
membranes without chorioamnioitis (11.4%), and GA lower than 27 weeks (11.4%) and
toxemia (9.6%). Only in 43 out of 136 patients (31.6%) who were on tocolytic
drugs, received AC. The schedule and doses were correct. According to the
inquiry, 48/68 (0.71) of obstetricians considered AC as definitively useful,
although only 22/68 (0.32) as very effective. The knowledge level was acceptable,
except in signaling with precision the neonatal problems that could be prevented,
as well as the lowest gestational age for use the AC. CONCLUSIONS: We considered
the use of AC in our institution as suboptimal. We found that the reasons for not
using them were not valid in most cases. Physician's attitudes to AC are positive
but it is not reflected on their clinical practice. It is necessary a strong
promotion of the usefulness of the AC for the preterm infant.
PMID- 11006644
TI - [Impact of prenatal steroids on morbimortality of eutrophic premature newborns].
AB - Although there is evidence that the use of prebirth steroids promote maturity of
premature newborn, in the United States of America it has been estimated that
only 50% of the women who have had a premature delivery (with babies with weight
between 501 and 1500 g) have been treated with steroids. We analyzed the
morbimortality and the need of assisted ventilation in 91 premature newborns with
gestational age of less than 34 weeks and weight of 1,500 g or less. They were
divided in two groups: one group included 50 newborns whose mothers received at
least one full course of steroids and the other group included 41 newborns whose
mothers did not receive it. Newborn pathologies, the need of assisted ventilation
and the mortality were higher in the group that did not receive prebirth
steroids. We conclude that the use of prebirth steroids diminishes the
morbimortality of the premature newborn.
PMID- 11006645
TI - [Flexible vaginal cast covered with oxidated cellulose. Surgical option in
neovagina for patients with Rokitansky-Kuster-Hauser syndrome].
AB - The alterations in differentiation of the mullerian derivatives and urogenital
sinus are a frequent cause of demanding attention in the gynecologist office.
Vaginal agenesis and hypoplasia are the representative events of alterations of
human sexual differentiation. Handling such conditions is in direct relationship
to the magnitude of the anatomical damage and the biopsychosocial consequences of
such pathologies. From historical perspective, several surgical techniques of
neovagina to correct such alterations have been described. We are presenting our
experience in surgical treatment of vaginal agenesis, as well as the aesthetic
functional outcomes obtained from a highly specialized hospital of the Health
Sector in Mexico City. Our patients attended the gynecologist office mainly
because of primary amenorrhea, anatomical alterations and sexual dysfunction. Tbe
age range varied between 19 and 28 years. Basic laboratory tests were conducted.
Urography, genetic studies, and a laparoscopic procedure were included. All the
women received psychological support. The diagnosis in all the cases was
Rokitansky Kuster-Hauser Syndrome with agenesis of the 2 proximal thirds of
vagina. A neovagina assisted by laparoscopy using a technique previously modified
was conducted. In such technique we use a flexible vaginal mould and oxide
cellulose to prevent fibrosis and surgical retraction. Cosmetic outcome was
satisfactory and dysfunction sexual was all improved. We conclude that our
procedure that includes the neovagina assisted by laparoscopy and the use of a
vaginal mould and oxide cellulose is a surgical option in those patients
presenting with vaginal agenesis and hypoplasia. This procedure improves the
aesthetic and sexual performances that are profoundly altered in such patients.
PMID- 11006646
TI - [Risk factors for cesarean section: epidemiologic approach].
AB - The increase in frequency of cesareans that has been noted through 70's, not
diminished--like it was expected--perinatal morbidity and mortality. The most
important indications to cesarean are distocias, previous cesarean and fetal
stress. In 1998 frequency of cesarean deliveries in our hospital was 35% of the
pregnancy attended. The claim of this study was to determine risks factors to
cesarean in our hospital. A case-control study was performed, selecting 165 cases
(cesareans) and 328 controls (via vaginal). It was determined OR of the risks
factors and atribuible fraction. Data were analyzed by X2. The most important
indications to cesarean delivery were: distocias (39%, n = 64); previous cesarean
(23%, n = 41) and fetal stress (11%, n = 21). There was not significative
differences in age, height and rupture membrane time in both groups. History of
cesarean delivery gave major risk to another surgical intervention (OR = 12.7, p
= < 0.0001, atribuible fraction 92%). Nuliparous (OR = 6.6, p < 0.00000,
atribuible fraction 85%), second gestation (OR = 1.8, p = 0.002) or history of
abortion (OR = 1.8, p = 0.04) were factors mainly associated to cesarean
delivery. We concluded that the precise 'medications of this surgical
intervention specially in nuliparous or previous cesarean delivery cases must be
replanteated to diminish its elevated frequency.
PMID- 11006647
TI - [Prognosis factors associated with the progression of preeclampsia to eclampsia].
AB - This study was undertaken to determine the prognosis value of laboratory and
clinical findings in the progression of preeclampsia to eclampsia. Nausea and
vomiting and glucose level > 105 mg/dL, serum creatinine level > 1.0 mg/dL,
aspartate aminotransferase level > 35 IU/L, alanine aminotransferase level > 40
IU/L and lactate deshiydrogenase level > 450 IU/L can be used to estimate the
risk for the advancement to eclampsia. This information could be helpful to the
clinician for management purposes.
PMID- 11006648
TI - [Obesity, arterial hypertension, metabolic disorders, and polycystic ovary
syndrome].
AB - OBJECTIVE: To determine the prevalence of central and general obesity, arterial
hypertension, and alterations in cholesterol, triglycerids, glycaemia and uric
acid levels in patients with PCOS and to compare them with women who do not
present this syndrome. To establish the possible association of this with the
PCOS. MATERIALS AND METHODS: This is a transversal analytic study. It includes
fifty-five cases of PCOS and fifty-five healthy controls from gynecologic and
familiar medicine consultation during the period from May 2nd to November 30th,
1999. It excludes patients with the Cushing disease, congenital suprarenal
hyperplasia, pregnant women or women under hormonal treatments until three months
prior the beginning of the study. The diagnostic of PCOS was established when the
patient presents three of the following characteristics: menstrual disturbances,
hirsutism, a LH/FSH relation > or = than 1.5 and ultrasound with polycystic
ovaries. Their weight and height was taken in order to calculate the body mass
index (BMI) and the waist/hip index (WHI) Blood samples in fasting where obtained
to determine the FSH, LH, cholesterol, triglycerids, glycaemia and uric acid
levels. Descriptive statistics where applied as well as the SPSS software along
with the Saphiro-Francia test, the Mann Whitney test and logistic regression.
RESULTS: The age of the patients with PCOS varied between 18 and 39 years old,
average 26.6 years old and that of the controls from 19 to 39 years old, average
28.2 years old, (p = 0.165). The prevalence of general obesity (BMI > or = 30)
was of 50.9% in the group of PCOS and of 18.2% in the group of controls. The
systolic hypertension (BP > or = 140 mm Hg) was of 9% against 7.3%. A diastolic
hypertension (BP > or = 90 mm Hg) of 25.5% against 7.3%. A hypercholesterolemia
(> or = 220 mg/dL) of 30.9% against 10.9%. A hypertriglyceridemia (> or = 160
mg/dL) of 30.9% against 16.4%. A hyperglycaemia(> or = 115 mg/dL) of 5.5% against
3.6% and a hyperuricemia(> or = 6.5 mg/L) of 23.6% against 3.6%. The OR
calculated through cross products showed that patients with PCOS have the
possibility of presenting obesity, hypercholesterolemia, hypertriglyceridemia,
hyperuricemia and diastolic hypertension, 4.6, 3.7, 2.3, 8.2 and 4.4 times more
than the controls. The comparison of the average of the variables of both groups
showed significant differences (p < 0.5) for the BMI, WHI, systolic BP,
cholesterol and uric acid. The multiple logistic regression showed a consistent
association between PCOS and hyperuricemia (MR = 5.23, = 1.4-26.26), obesity (MR
= 3.26, CI = 1.33-8.01) and hypercholesterolemia (RM = 3.04, CI = 1.02-9.08).
CONCLUSIONS: The study showed a higher prevalence of obesity,
hypercholesterolemia, hypertriglyceridemia, hyperuricemia and diastolic
hypertension in patients with PCOS than in the controls. No such thing for
hyperglycaemia and systolic hypertension. Nevertheless, there are significant
differences between both groups related to the BMI, WHI, systolic hypertension,
hypercholesterolemia and hyperuricemia. A consistent association among the PCOS
and hypercholesterolemia, obesity and hyperuricemia was found.
PMID- 11006649
TI - Physicians' greatest enemy--complacency!
PMID- 11006650
TI - Epidemiology of neural tube defects, Hawaii, 1986-1997.
AB - Neural tube defects (NTDs) in Hawaii between 1986 and 1997 were examined using
data from a statewide birth defects surveillance system. The prevalence increased
significantly over the twelve-year period. NTD prevalence did not appear to vary
by place of residence. The relationship of type of defect, maternal age, and
infant/fetus sex was similar to that reported in the literature.
PMID- 11006652
TI - Emphysematous pyelonephritis.
AB - Emphysematous pyelonephritis is a rare, severe, necrotizing form of renal
infection characterized by the presence of gas within the renal parenchyma or
perinephric space. In patients suspected of emphysematous pyelonephritis,
computed tomography scan should be done promptly. Based on the available data and
this case, surgical intervention appears to be the preferred treatment.
PMID- 11006651
TI - Alcohol use in Hawaii.
AB - This article provides a review of the existing literature on alcohol use in
Hawaii (i.e., epidemiology, reasons for use, associated problems, and
intervention) and offers clinical implications of the findings and suggestions
for further areas of research. In general, Caucasians, Hawaiians, younger
Filipinos, males, adolescents, young adults, and those with lower educational
attainment were found to be at higher risk. Overall, Hawaii's rates were either
comparable or lower than those for the entire United States. Factors associated
with different rates of alcohol use included accessibility, ability to resist
offers, parent use and sanctions, peer influence and use, attitudes and beliefs
(e.g., perceived normal drinking, dangerousness), religious affiliation, social
occasions, and school intervention. Variable rates and trends in help-seeking
behaviors, treatment admissions, and treatment utilization reflected the socio
cultural diversity in Hawaii. Perceived effectiveness of different treatments
were generally consistent across ethnic groups, but did not necessarily represent
actual efficacy. There is a clear need for additional prevention, screening, and
intervention programs in Hawaii, including socio-culturally appropriate ones, as
well as a need for further research.
PMID- 11006653
TI - Symptomatic human rotavirus subgroups, serotypes & electropherotypes in
Hyderabad, India.
AB - A total of 352 stool specimens obtained from children under 2 yr of age with
acute diarrhoea, between January 1998 and March 1999, were screened for the
presence of rotavirus by RNA-PAGE. Symptomatic human rotaviruses were detected in
57 of 352 (16.19%) specimens by RNA-PAGE. These 57 samples were tested for
rotavirus double stranded RNA pattern and among these, 46 samples were tested for
subgroup and serotype specificities. Among the 46 strains tested, 29 strains were
found to be subgroup II and remaining 17 strains were subgroup I, indicating that
subgroup II strains are more predominant than subgroup I strains. Subgroup I and
II strains were circulating concurrently throughout the study period. Seventeen
strains with 'short' RNA pattern and subgroup I specificity could not be assigned
as serotype 2 strains as they exhibited cross-reactivity to MAbs specific for
more than one serotype. Of the 29 subgroup II strains with 'long' RNA pattern, 16
(55.17%) were serotype 1, 8 (27.58%) were serotype 4. Five (17.24%) showed dual
reactivity to serotypes 1 and 3. Our results indicated that serotype 1 and G2
like strains are predominant in Hyderabad. None of the virus strains showed an
unusual RNA pattern.
PMID- 11006654
TI - Detection of faecal leucocytes & erythrocytes from stools of cholera patients
suggesting an evidence of an inflammatory response in cholera.
AB - BACKGROUND & OBJECTIVES: Detection of faecal leucocytes and RBCs in stool samples
of cholera patients has been reported in a small number of studies. This study
extends these observations by examining stool samples of cholera patients in
Calcutta. METHODS: Out of 1562 diarrhoeal stool samples, Vibrio cholerae was
isolated in 266 cases. Stool samples obtained were examined microscopically
within two hours of collection. RBCs and faecal leucocytes were examined by
normal saline and methylene blue stain. Stool culture was performed using
selective and differential media for isolation of V. cholerae. RESULTS: Among 266
cholera patients, RBCs was detected in 58 per cent and faecal leucocytes in 88
per cent respectively. The extent of the changes correlated with clinical
severity. INTERPRETATION & CONCLUSION: This study showed the presence of RBCs and
faecal leucocytes in stools of patients of cholera caused by V. cholerae 01 and
0139 which indicates some inflammatory changes in the gut mucosa. Further study
is required to elucidate the inflammatory mechanism involved in the underlying
process(es).
PMID- 11006655
TI - Role of the male partner in the lower genitourinary tract infection of female.
AB - We studied the relationships of selected microbes and the role of consorts in the
causation of vaginal discharge which may be due to cervicitis or vaginitis. A
total of 93 consecutive patients in the reproductive age group with symptoms of
vaginal discharge along with their sexual partners were studied. Samples were
collected from the cervix and posterior fornix of the female patients and from
the urethra and sub-prepucial area of the male partner for culture of Neisseria
gonorrhoeae, Gardnerella vaginalis, Mycoplasma hominis, ureaplasma, candida,
aerobic and anaerobic organisms. Apart from cultures, KOH and Gram stain of the
discharge were made. Predominant pathogen isolated was Ureaplasma urealyticum
from 40 (43.01%) females and 23 (24.7%) males. The next common pathogenic
organisms isolated were candida species from 11 (11.8%) females and 5 (5.4%)
males and Chlamydia trachomatis in 3 (3.2%) females and 1 (1.1%) male. Various
organisms were more frequently isolated from the 29 of 43 (67.4%) couples who had
had sexual intercourse 7 days prior to the recruitment as compared to 14 of 43
(32.6%) who had had coitus more than 7 days prior to their recruitment. This may
be due to the spontaneous disappearance or decrease in the number of organisms to
the level that they could be detected by culture. In our study, 6 (6.5%) of male
partners carrying pathogenic organisms were asymptomatic, indicating that their
screening and treatment is vital.
PMID- 11006656
TI - The effects of clofazimine, niclosamide & amphotericin B, on electron transport
of Leishmania donovani promastigotes.
AB - BACKGROUND & OBJECTIVES: The study was undertaken to explore the locus of
interaction of clofazimine and niclosamide which showed substantial growth
inhibition property in Leishmania donovani promastigotes. METHODS: The uptake of
final electron acceptor oxygen and 2,6-dichlorophenolindophenol (DCPIP) reduction
in the electron transport chain were measured by constant volume Warburg
respirometer and monitoring absorbance at 600 nm, respectively. Irreversibility
of O2 uptake inhibition by clofazimine and niclosamide was determined by dilution
of cell suspension followed by centrifugation. RESULTS: Clofazimine and
niclosamide showed their minimum inhibitory concentration (MIC) at 33 and 150
micrograms/ml, respectively. Oxygen uptake inhibition by clofazimine and
niclosamide was not reversed by removal of the drug by centrifugation. Rotenone,
a potent inhibitor of mammalian electron transport chain showed no inhibition on
the electron transport chain of L. donovani promastigotes. Cyanide at 1 mM
concentration showed partial inhibition in L. donovani promastigotes. Oxygen
uptake and DCPIP reduction by L. donovani promastigotes were highly sensitive to
sulphhydryl group inhibitors. Strong inhibition of oxygen uptake (80-100%) by L.
donovani promastigotes was achieved by clofazimine, niclosamide and amphotericin
B. Amphotericin B failed to inhibit DCPIP reduction by L. donovani promastigotes,
whereas DCPIP reduction was inhibited by clofazimine and niclosamide,
respectively. INTERPRETATION & CONCLUSION: DCPIP reduction was mediated by
transplasma membrane electron transport as evidenced by its inhibition with
membrane impermeable quinone 1,2-naphthoquinone-4-sulphonic acid (NQSA).
Transplasma membrane electron transport requires b-cytochromes and sulphhydryl
groups for its function and was inhibited by clofazimine and niclosamide.
PMID- 11006657
TI - Air pollution in Calcutta elicits adverse pulmonary reaction in children.
AB - BACKGROUND & OBJECTIVE: Pulmonary responses of children chronically exposed to
ambient air pollution in Calcutta have been investigated. METHODS: A total number
of 153 children from Calcutta and 116 from rural West Bengal in the age group of
6-17 yr were included in this study. Respiratory symptom complex, sputum cytology
and micronucleus (MN) count of buccal epithelial cells were evaluated. Blood
smears were examined for WBC differential count and RBC morphology. RESULTS:
Marked rise in respiratory symptoms (43% in urban vs 14% in rural) and sputum
alveolar macrophage (AM) number was observed in urban children compared to their
rural counterparts (14.2 +/- 1.4 AM/hpf vs 6.7 +/- 1.4 AM/hpf, mean +/- SE, P <
0.001). The urban group also demonstrated increased numbers of neutrophils,
eosinophils and iron-laden AM in their sputum. Besides, buccal epithelial cells
of urban children exhibited higher MN frequency than their rural counterparts
(0.22 vs 0.17%, P < 0.05). While sputum neutrophilia and eosinophilia suggest
inflammatory and allergic lung reactions, elevated MN count is indicative of
greater genotoxic effect on the exposed tissues of urban children. Hypochromic
red cells in peripheral blood smear was a common finding in both urban and rural
groups, but eosinophils and monocytes were present in elevated frequencies in the
rural children. INTERPRETATION & CONCLUSION: The study demonstrated that children
inhaling grossly polluted air of Calcutta suffer from adverse lung reactions and
genetic abnormality in the exposed tissues.
PMID- 11006658
TI - Dimensions & shape of the trachea in the neonates, children & adults in northwest
India.
AB - Measurements of the trachea and the two main bronchi including the subcarinal
angle and the angles of the bronchi with the vertical were taken in specimens
obtained from 370 adults, 60 children and adolescents up to 17 yr and 27 dead
newborns. These measurements showed a gradual increase with age up to a certain
point (often 31-35 yr in males and 26-30 yr in females) and stabilised
thereafter. There was no sexual dimorphism in measurements till the age of 17 yr
and thereafter, the measurements were greater in males than in females (P <
0.001). In adults the body weight and supine body length had a significant
correlation with certain measurements of the trachea. The subcarinal angle and
the angles of the two main bronchi with the vertical were variable but the angle
of the right bronchus with the vertical was always found to be smaller than that
of the left. The incidence of different shapes of the trachea at transversely cut
upper end was also studied. A U-shaped trachea was present in 33.2 per cent male
adults but was not seen in females. This may have some medico-legal importance.
PMID- 11006659
TI - Should infantile hypertrophic pyloric stenosis be managed in specialist centres?
PMID- 11006660
TI - Preoperative anaesthesia information--what do patients need to know?
PMID- 11006661
TI - Thrombolytic therapy in acute myocardial infarction: Third Irish Working Party
Consensus. Irish Thrombolysis Concenus Group.
PMID- 11006662
TI - Infantile hypertrophic pyloric stenosis in a regional centre.
AB - BACKGROUND: It has been suggested that only specialist paediatric surgeons should
manage infantile hypertrophic pyloric stenosis (IHPS). AIM: The aim of this
retrospective study was to ascertain whether the majority of these infants might
be managed in a well-equipped regional centre. METHODS: Using the Hospital
Inpatient Enquiry database, all cases of IHPS within a single administrative
health region were identified over a six-year period. A chart review was
performed to obtain demographic and clinical information for each patient.
Reports from the Central Statistics Office were used to obtain data on population
and live births for the region. RESULTS: Seventy patients with IHPS were
identified from this region from 1991 to 1996, 63 (90%) of which were treated in
the region. Of the remaining seven, four were referred directly to specialised
paediatric surgical hospitals because of prematurity (n = 1), low birth weight (n
= 1), capillary haemangioma (n = 1) and severe metabolic derangement (n = 1)
while three were assessed and treated in general hospitals outside the region. Of
the 63 infants undergoing pyloromyotomy in this region, the duodenal mucosa was
breached in four (6%); there were wound complications in three (5%); and one
required a re-pyloromyotomy. The mean postoperative stay was eight days (range 2
42 days). CONCLUSION: The majority of infants with IHPS may be safely managed in
regional centres with transfer to specialist paediatric centres reserved for
'high risk' cases. The management of IHPS at a regional level has important
implications and presents opportunities for surgical training.
PMID- 11006663
TI - Management of head injury in a regional hospital.
AB - BACKGROUND: Concern about delay in the treatment of serious head injury may
result in unnecessary transfer to neurosurgical units for scanning and
neurosurgical assessment. AIMS: This study assessed the management of head
injuries in a regional hospital with computed tomographic (CT) and 'image-link'
facilities allowing instantaneous transmission of CT scans to the regional
neurosurgical unit for specialist assessment. METHODS: A retrospective study was
carried out of all head injuries presenting to Limerick Regional General Hospital
in a single year. Data gathered included mechanism of injury, mode of transfer,
requirement for admission and length of stay. Neurological status was assessed
using the Glasgow Coma Scale (GCS) and functional status using the Glasgow
Outcome Scale. RESULTS: Between January and December 1995, 1,564 patients
presented with head injuries to the accident and emergency (A/E) department of
Limerick Regional General Hospital. Twenty (1%) were dead on arrival, 12%
required hospital admission and the remainder were discharged after assessment.
Seventy-six per cent were males and 74% under 40 years of age. Among the 194
patients requiring hospital admission, 14% had a skull fracture and 22 had a
severe head injury. CT brain scans were performed in 43 patients and were
abnormal in 42%. On the basis of CT and clinical findings, six patients were
transferred immediately for a neurosurgical procedure and one was transferred
later following clinical deterioration. CONCLUSIONS: A CT scan and image-link
facility permitting remote neurosurgical advice allows the majority of patients
with head injury to be safely managed in well-equipped regional units without
onsite neurosurgical expertise.
PMID- 11006664
TI - Regional vascular surgical units: a practical means of providing specialist
services.
AB - BACKGROUND: A comprehensive regional emergency and elective vascular surgical
service was established in Limerick Regional General Hospital between 1994 and
1996 following the appointment of three surgeons with vascular training. AIM: To
compare vascular surgical activity before and after the establishment of a
regional vascular service. METHODS: This study used local and national
computerised databases, clinic letters, theatre registers and radiology records
to compare vascular surgical activity before (1992) and after (1997) this service
was established. RESULTS: Total outpatient activity increased almost six-fold and
total number of inpatient vascular procedures (including radiological) increased
from 146 to 432, but the venous proportion declined from 70% to 36%. The number
of major arterial procedures increased from 37 to 165 in 1997 including 10
carotid endarterectomies, 24 aortic reconstructions and 54 lower limb
reconstructions representing rates of 3/100,000, 8/100,000 and 17/100,000
population respectively. CONCLUSION: As substantial changes in disease patterns
are unlikely, these data indicate that patients previously diverted elsewhere for
therapy are now cared for within the health board region and that further
increases in workload may be expected. We suggest that these data mandate the
reallocation of resources to fund appropriately staffed and audited regional
vascular units.
PMID- 11006665
TI - Prevalence and aetiology of leg ulcers in Ireland.
AB - BACKGROUND: The prevalence of leg ulcer disease in Ireland has been poorly
documented. AIMS: This study aimed to investigate the aetiology and prevalence of
leg ulcers in one health district. METHODS: All patients receiving healthcare for
an active leg ulcer in the Mid-Western Health Board (MWHB) region of Ireland
(population: 317,069) were identified in a defined two-month period. A cross
sectional survey of all healthcare workers providing care to patients with leg
ulceration was carried out. Patients with leg ulcers of uncertain cause were
invited for follow-up assessment to establish the underlying cause. RESULTS:
There were 389 patients with leg ulcers with a mean (standard deviation [SD]) age
of 72.3 (11.1) years. The prevalence was 0.12% but it was 1.03% in patients aged
70 years and over. Women were twice as likely to be affected. Venous disease
accounted for 81% of ulcers, and arterial disease for 16.3%, while ulceration due
to diabetic neuropathy and rheumatoid vasculitis was unusual. CONCLUSION: Leg
ulcers are an important source of morbidity in our ageing population. Effective
treatment programmes could diminish the impact of this debilitating disease on
the health service.
PMID- 11006666
TI - Patients' knowledge of perioperative care.
AB - BACKGROUND: Patient knowledge of perioperative care, particularly the role of the
anaesthetist, appears limited. AIM: This study investigated patients' knowledge
of common medical terms, of their surgical care, of the role of the anaesthetist,
and their preoperative fears and concerns about postoperative pain. We examined
the changes in their knowledge base as a result of the pre-anaesthetic visit and
their inpatient stay. METHODS: Three hundred patients were surveyed on three
separate occasions, before a routine pre-anaesthetic visit, two to three hours
after this visit and on the day of discharge from hospital. RESULTS: Patients'
knowledge of medical terms, their surgical procedure, and the role of the
anaesthetist in their perioperative care were limited. There was little change
following either the pre-anaesthetic visit or postoperative convalescence.
Misconceptions, about such issues as postoperative pain, appeared to increase by
the end of their hospital stay. Male patients, older patients and patients in
lower socio-economic groups had poorer knowledge. A significant proportion of
patients remained unaware that the anaesthetist was medically qualified.
CONCLUSIONS: Patients' knowledge of perioperative care is limited, with very
little change during hospital stay. Novel educational approaches may be required
to increase basic medical knowledge.
PMID- 11006667
TI - The management of ureteric calculi without extracorporeal shock-wave lithotripsy.
AB - BACKGROUND: Extracorporeal shock-wave lithotripsy (ESWL) is a relatively new
technological adjunct in the treatment of renal calculi, but availability is
limited. AIM: The aim of this study was to assess the outcome of ureteroscopic
procedures in a unit without on-site ESWL facility. METHODS: A retrospective
study of all cases of ureteric calculi presenting to this hospital during the
period 1991 to 1997 was performed. RESULTS: One hundred and thirty five patients
with a mean age of 46.8 years were evaluated. Ninety-four (69.5%) had their stone
successfully manipulated and/or extracted at ureteroscopy. Using strict criteria,
41 patients (30.5%) had failed ureteroscopies. Fourteen (10.4%) suffered
complications related to their ureteroscopy, thirteen had their complications
treated conservatively and three (2.3%) needed open procedures. CONCLUSION:
Ureteroscopy has a high success rate and low morbidity. We continue to advocate
ureteroscopy in the initial management of ureteric calculi.
PMID- 11006668
TI - Profile of attendance at a maternity hospital emergency room.
AB - BACKGROUND: Direct presentations to secondary care that could have been managed
in primary care have been the subject of much study. Social factors may influence
the decision to present directly to secondary care services. AIM: To determine
the profile and primary care service use of patients attending a maternity
hospital emergency room (ER). METHODS: A self-administered, questionnaire based,
cross-sectional study was performed over a period of one month. RESULTS: Of 350
patients attending the ER, 343 (98%) completed a questionnaire. Mean age of
patients attending was 28 years (range 16-65). Thirty seven per cent were
eligible for free medical care and 39% belonged to socio-economic group six.
Fifty nine per cent attended outside normal hours, 31% had a female general
practitioner (GP) and 38% were referred by a GP to the ER. Twenty eight per cent
had seen their GP in the previous three days, 31% had consulted a GP with their
current problem and 58% felt "comfortable" or "very comfortable" attending their
GP with a gynaecological complaint. CONCLUSIONS: This study indicates that the
service is responsible for a considerable workload, with a low level of use of
primary care services by those attending.
PMID- 11006669
TI - Need-based waiting lists for hip and knee arthroplasty.
AB - BACKGROUND: Need-based waiting lists have been shown to offer advantages over
traditional time-based waiting lists. This study investigated the effect of their
introduction in our orthopaedic practice. METHODS: Each patient on the waiting
list for total hip replacement (n = 240) and total knee replacement (n = 98) was
invited to attend a dedicated assessment clinic. At the clinic each patient had a
joint score (Harris Hip Score or American Knee Society Score) calculated.
Patients with the lowest joint scores were moved to the top of the waiting lists.
Scores were repeated postoperatively. RESULTS: Validation of the hip replacement
and knee replacement waiting lists reduced them by 20% and 11% respectively. The
efficiency and transparency of the service were increased. CONCLUSION: Need-based
waiting lists are easily introduced and offer significant advantages over time
based waiting lists. We advocate their introduction in other centres.
PMID- 11006670
TI - A comparison of outcome scores in os calcis fractures.
AB - BACKGROUND: Of over 20 different scoring systems to evaluate outcome following
calcaneal fracture, the Maryland Foot Score has broad current acceptance. A
general health survey, the Short Form 36 (SF 36) has also been used. AIMS: The
study compared two scoring systems for assessing the outcome of open reduction
and internal fixation of displaced intra-articular calcaneal fractures. METHODS:
Over a four-year period, 31 displaced intra-articular calcaneal fractures were
categorised by the Sanders classification and treated by open reduction and
internal fixation. Outcome was assessed by the Maryland Foot Score and by the
Short Form 36 (SF 36) general health questionnaire. RESULTS: Thirty-five per cent
of fractures were Sanders class 2, 57% were class 3 and 8% were class 4. The
average follow-up was 2.5 years (range 1-4 years). Using the Maryland Foot Score,
seven fractures had an excellent result, 13 had a good result, six had a fair
result and one was a failure. There was a correlation between pain (coefficient =
0.780, p < 0.001) and physical function (coefficient = 0.638, p < 0.001) with the
appropriate sections of the SF 36. CONCLUSION: The Maryland Foot Score measures
what it attempts to measure and therefore it has content validity for pain and
physical function.
PMID- 11006671
TI - Assessment of hepatitis C infection in injecting drug users attending an
addiction treatment clinic.
AB - BACKGROUND: Injecting drug users represent a high risk group for hepatitis C
(HCV) infection. Currently, screening of this group for HCV is inconsistently
implemented. AIM: We designed a HCV assessment algorithm and sought to determine
the frequency with which injecting drug users completed the assessment process.
METHODS: Prospective study of a HCV assessment algorithm in the setting of a
specialist outpatient addiction treatment clinic. Participants consisted of
consecutive new attenders over a six-month period with a history of injecting.
RESULTS: Only 21 (18%) of 119 patients reached a satisfactory endpoint of
assessment. Forty-eight injectors were tested for antibody to HCV, of whom 26
(54%) tested positive. Thirteen of those with positive test results were no
longer attending when the test result became available. Only four of the 19
patients who were referred, attended the on-site hepatology clinic. CONCLUSIONS:
Thorough screening of injecting drug users for HCV within one treatment service
is difficult. There is a need for explicit policies on this issue involving co
operation between primary care providers and addiction services and hepatology
services.
PMID- 11006672
TI - Methadone maintenance in general practice: impact on staff attitudes.
AB - BACKGROUND: The evaluation of a structured protocol for the discharge of
stabilised patients on methadone maintenance to general practice provided an
opportunity to evaluate the impact on the attitudes of general practitioners
(GPs) and practice staff. AIM: To assess attitudes, expectations and experience
among GPs and practice staff before the introduction of structured methadone
maintenance and six months after its introduction. METHODS: A postal
questionnaire was sent to 31 GPs and 23 receptionists in 23 Dublin general
practices before the patient's first visit and six months later at the end of the
study period. Outcome measures were staff attitudes, incidence of disruption,
perceived difficulties in providing care and in prescribing methadone, and stress
levels. RESULTS: There was a generally positive attitude to provision of
methadone in general practice for stabilised patients, although it was not
anticipated to be problem free. Following six months involvement attitudes were
similar; stress levels were unchanged, but fewer GPs anticipated problems in
delivering the service. All continued to participate in the scheme. CONCLUSION:
GPs and receptionists in this sample had mixed views about methadone maintenance
which were unchanged by six months experience of the service. The study
illustrates important issues in the recruitment and support of general practice
in meeting this need.
PMID- 11006673
TI - Population characteristics of Irish Helicobacter pylori isolates: a tRNA
associated locus.
AB - BACKGROUND: A strain-variable transfer RNA-associated-locus (trl) was present in
50% of Irish Helicobacter pylori (H. pylori), isolates and did not correlate with
the origin of the isolates. AIM: To associate a particular genotype or phenotype
to trl status in H. pylori by further screening the isolates from the original
study for the presence of known genotypic and phenotypic characteristics.
METHODS: Forty two clinical isolates were screened for the presence of the cagA,
vacA, iceA1 and vapD genes by Southern or DNA dot blot analysis. Western blot
analysis was performed using antibodies to CagA, VacA, Lewis X (Le(x)) and Lewis
Y (Le(y)). Plasmids were identified by the alkaline lysis method. RESULTS: The
cagA gene was present in 29 (69%) of isolates screened and 21 (50%) produced the
CagA protein. The vacA gene was detected in all of the isolates while VacA was
expressed in 71.4%. The iceA1 and vapD loci were detected in 73.8% and 71.4%
respectively. Le(x) was expressed in 42.9% and Le(y) in 38.1% of the isolates.
Expression of both Lewis antigens was detected in 7.1% while in 30.9% neither
antigen was detected. Plasmids were present in 47.6%. There was no association
between the trl status of isolates and any of the above. There were no
significant associations between the phenotypic and genotypic characteristics
studied and peptic ulcer disease or non-ulcer dyspepsia. CONCLUSION: The strain
variable tRNA-associated locus is independent of the vacA/VacA, cagA/CagA, Lewis
X, Lewis Y, iceA1, vapD and plasmid status in the population of Irish H. pylori
isolates studied.
PMID- 11006674
TI - Acute forearm compartment syndrome: report of three cases and a review of the
literature.
PMID- 11006675
TI - The Irish Journal of Medical Science--a historical outline.
PMID- 11006676
TI - Idiopathic mesenteric thrombosis following caesarean section.
PMID- 11006678
TI - Intussusception in adults: a rare entity.
PMID- 11006679
TI - The roots of youth violence.
PMID- 11006677
TI - Unusual case of pilomatricoma.
PMID- 11006680
TI - Reaching communities of children.
PMID- 11006681
TI - Troubled kids, troubled times.
PMID- 11006682
TI - Boys and their toys.
PMID- 11006683
TI - Babes in arms. Juvenile access to guns in Minnesota.
PMID- 11006684
TI - Striking back.
PMID- 11006685
TI - Media violence. The harsh reality.
PMID- 11006686
TI - Interactive media violence and children.
PMID- 11006687
TI - Protecting youth from harm.
PMID- 11006688
TI - Promising approaches to youth violence prevention.
PMID- 11006689
TI - Beyond treating the wounds. The physician's role in preventing gun violence.
PMID- 11006690
TI - Listening to rural Minnesota.
PMID- 11006691
TI - Pediatric firearm injury in Minnesota, 1998. Fatal and nonfatal firearm injuries
among Minnesota youth.
AB - OBJECTIVE: Minnesota hospitals began to assign E-codes (external cause of injury)
to hospital discharge data in 1998. It is now possible to describe the
epidemiology of medically treated firearm injury (FI) cases in Minnesota by
combining hospital discharge data with injury data from other sources. This
population-based investigation provides a preliminary epidemiologic description
of fatal and nonfatal firearm injuries in children and adolescents in Minnesota
during 1998. METHODOLOGY: Pediatric firearm injury cases were identified from the
Minnesota Department of Health's Minnesota Trauma Data Bank, a population-based
data system for injury surveillance in Minnesota. To qualify for the study, the
patients had to be Minnesota residents, younger than 20 years old at the time of
injury, and injured by a firearm in 1998. RESULTS: The 175 cases identified
yielded on overall FI rate of 12.5/100,000, a mortality rate of 2.4/100,000, and
a nonfatal to fatal ratio of 4.1:1. Eighty-five percent of patients were male;
15% female. The largest proportion of firearm injuries were assault-related
(45%), followed by unintentional (34%), and self-inflicted (15%). Adolescents
aged 15-19 years accounted for 79% of the injuries, and children 14 or younger,
21%, yielding rates of 37.6/100,00 and 3.5/100,000, respectively. Twenty-two
percent of 15-19-year-olds and 11% of children 0 to 14 died, yielding mortality
rates of 8.1/100,000 and 0.4/100,000, respectively. Where race was documented,
whites represented 53% of the cases; African Americans, 32%; Native Americans,
8%; and Asian/Pacific Islanders, 7%; yielding race-specific rates of 4.1/100,000,
54.3/100,000, 30.5/100,000, and 12.1/100,000, respectively. Sixty-six percent of
the patients were residents of the Minneapolis/St. Paul metro area and 33% were
residents of Greater Minnesota, yielding rates of 16.0/100,000 and 8.6/100,000,
respectively. In the Twin Cities metro area 24% of injury cases were
unintentional, 5% were self-inflicted, 65% were assaultive, and 6% were
undetermined. In Greater Minnesota 53% were unintentional, 33% were self
inflicted, 9% were assaultive, and 5% were undetermined. CONCLUSIONS: Minnesota's
1998 rates for firearm injury were less than half the 1997 national rate. The
state's FI rates show significant disparities by race and region of residence.
More FI data will have to be collected over more years to describe and identify
trends and multifactor relationships. Policymakers need to ensure that firearm
injury continues to be monitored and assessed in Minnesota.
PMID- 11006692
TI - Firearm-related suicide in Minnesota. A picture of morbidity and mortality.
PMID- 11006693
TI - Calculating the costs of gun injuries. A new methodology.
AB - A new method for assessing the costs of gun injuries to a health system examines
data on paid amounts, comprehensive medical expenses, and expenses over time. The
authors extracted claims using injury diagnosis codes from billing forms and
medical charts. The study demonstrates that a claims database can be used to
accurately measure health care costs associated with gun injuries. The study is
the first to include gun-related injuries treated in ambulatory care settings and
to track actual payments over time.
PMID- 11006694
TI - [Recurrent thoracic pain without findings. Let the endoscope evaluate the
situation!].
PMID- 11006695
TI - [Space-occupying lesion in the liver? Don't immediately refer for expensive CT
examination!].
PMID- 11006696
TI - [More rapid recovery after fracture. When can ultrasound accelerate healing?.
Interview by Petra Eiden].
PMID- 11006697
TI - [Sports or hormones for aging men? When Adam suffers from PADAM (partial androgen
deficit of the aging man)].
PMID- 11006698
TI - [After-care in breast carcinoma. Medical examination and mammography compared].
PMID- 11006699
TI - [New therapeutic approaches in advanced breast carcinoma. Palliative measures are
increasingly more tolerable].
AB - Advances in palliative chemotherapy are based on the development of new
substances or new treatment strategies, such as, for example, high-dose
chemotherapy. New cytostatic agents are developed with the aim of improving
therapeutic efficacy and tolerability. Taxanes rapidly became part of standard
treatment, and their combination with the anthracyclines represents the most
effective treatment currently available. Liposomal encapsulation of
anthracyclines can reduce their cardiotoxicity without loss of efficacy. Recent
antimetabolites and the vinca alkaloid, vinorelbine, combine a good antitumoral
effect with a favorable toxicity profile. The use of the monoclonal antibody,
trastuzumab, has made specific immunotherapy possible for the first time. The
role of high-dose chemotherapy remains uncertain, and further randomized studies
are urgently needed.
PMID- 11006700
TI - [Resection of the sentinel lymph node in breast carcinoma. Substitution for
axillary lymph node excision?].
PMID- 11006701
TI - [With hypobaric pressure to diagnosis. Vacuum punch biopsy allows for minimally
invasive sample study].
PMID- 11006702
TI - [Internet addresses on the main topic. Breast carcinoma].
PMID- 11006703
TI - [New guidelines for resuscitation. Mouth-to-mouth resuscitation and 100
compressions per minute].
PMID- 11006704
TI - [Human granulocytic ehrlichiosis. New tick bite disease lies in wait also in
German forests].
AB - HGE is an uncommon zoonosis, transmitted to humans by ticks (Ixodes ricinus).
Heavily exposed persons, such as foresters and forestry workers, are most at risk
of infection. HGE usually runs an asymptomatic and self-limiting course. Symptoms
include acute pyrexial illness, frequently accompanied by muscle pain, headache,
nausea and vomiting. Treatment is with doxycycline/tetracycline or rifampicin. In
a study in Hesse of 128 heavily exposed subjects, 19.5% had serum antibodies (IFA
test) against HGE versus 4.4% in a control group. This difference is
statistically significant. The prevalence of both symptoms and the seropositivity
differ significantly between locations. HGE should be considered in the
differential diagnosis of fever of unknown origin following tick bite exposure,
at least in the North Hesse region.
PMID- 11006705
TI - [Guidelines for lowering lipids are too infrequently observed. Results of a
retrospective study of coronary heart disease patients].
AB - The aim of this retrospective analysis was to investigate adherence to treatment
guidelines in the secondary prevention of coronary heart disease. 3720 CHD
patients treated in 591 doctor's offices throughout Germany were investigated.
End points were serum lipid levels at week-6, i.e. screening investigation, and 5
weeks after discontinuation of the lipid-lowering medication (week-1). 3383 of
the 3720 (90.9%) patients had LDL-C levels > = 115 mg/dl, and 3563 (95.8%) > =
100 mg/dl. At week-6 mean LDL-C was 167.7 +/- 43.5 and mean total cholesterol was
258.8 +/- 47.8 mg/dl. 5 weeks after discontinuation of lipid-lowering treatment,
mean LDL-C increased by 5.6%, and mean total cholesterol by 3.7% in comparison
with baseline at week-6. 2346 (69.3%) of the patients with LDL-C > = 115 at week
6 did not receive any prior lipid-lowering medication. Also, patients receiving
lipid-lowering medication demonstrated an insufficient lipid decrease (only 14.4%
of all treated patients had LDL-C levels < 115 mg/dl, and only 6.8% had levels <
100 mg/dl. CONCLUSION: So far, lipid-lowering guidelines for the secondary
prevention of CHD are not being adequately implemented. Appropriate action to
remedy this situation (e.g. establishment of Disease Management Programs) is
needed. The aggressive use of lipid-lowering drugs is a must if the goals of the
treatment guidelines are to be met, and morbidity and mortality of CHD lowered.
PMID- 11006706
TI - [Thrombosis ABC, 19: Lung embolism. When thrombosis becomes an emergency].
PMID- 11006707
TI - [Diagnostic quiz. Thoracic pain in a young woman. Acute posterior wall infarct].
PMID- 11006708
TI - [Senile macular degeneration. Photodynamic therapy stabilizes vision].
PMID- 11006710
TI - [Therapy of allergic conjunctivitis].
AB - Among the several eye diseases (or diseases involving the eye) based on
hypersensitivity reactions, the most frequent is allergic conjunctivitis.
Recently six types of allergic conjunctivitis/keratoconjunctivitis are
distinguished: 1. seasonal, 2. perennial, 3. vernal, 4. giant papillary, 5.
atopic and 6. of contact origin. Their treatment is generally local. In the most
frequent seasonal ("hay fever") and perennial forms the elimination of the
allergen or when it is impossible antihistamines (with or without
vasoconstrictors), "weak" steroids or hyposensitisation are offered. In vernal
and atopic keratoconjunctivitis mast cell stabilizers are the most effective,
with special effect of lodoxamide in the vernal type. In giant papillary and
contact allergic inflammations the elimination of the causative agent is the
first method of choice. In resistant cases "strong" steroids, in extreme forms
immunosuppressive, cytostatic and systemic treatment may become necessary. The
paper gives a review of currently applied medicines (mainly eyedrops) and other
methods of treatment, and includes therapeutic principles applying to various
forms of allergic conjunctivitis.
PMID- 11006709
TI - [Pathogenesis and types of neonatal diabetes].
AB - Studies on pathogenesis of neonatal diabetes may lead to better understanding of
pancreatic beta-cell maturation and regulation of insulin secretion. The purpose
of this study was to examine the clinical course, immunologic and genetic
background of the transient and permanent form of neonatal diabetes. Clinical
data (onset and duration of diabetes, C peptide levels, duration of insulin
treatment, associated disorders) were collected, islet cell specific antibodies
(islet cell antibody and glutamate decarboxylase antibody) were determined and
genetic analyses (HLA DQA1-DQB1 typing and microsatellite mapping on chromosome
6) were performed in three patients with permanent and three patients with
transient neonatal diabetes. None of the six patients had HLA DQ diabetes
susceptibility alleles and most infants were negative for islet cell
autoantibodies indicating that no pancreatic islet-cell specific autoimmunity
exists in the two forms of neonatal diabetes mellitus. Complete paternal
uniparental isodisomy of chromosome 6 has been identified in a transient neonatal
diabetes case with macroglossia. The permanent neonatal diabetes cases and the
other two cases with transient form did not possess this chromosome anomaly. It
is concluded, that none of the two forms neonatal diabetes is of autoimmune
origin. They have different genetic background and represent different disease
entities. Transient neonatal diabetes is probably caused by alteration of
expression of an imprinted gene on chromosome 6 which might play role in fetal
growth and pancreatic beta-cell maturation and insulin secretion. Permanent
neonatal diabetes is probably a more heterogenous phenotype, the cause of which
remains to be clarified in the future.
PMID- 11006711
TI - [Effectiveness of Lisinopril in the treatment of heart failure].
AB - A prospective study was performed in patients (30 M, 16 F, mean age of 56.0 +/-
9.2 [42-73] years) with congestive heart failure to assess the efficacy of
lisinopril during a 16 weeks treatment period. Changes in clinical signs,
functional capacity, blood pressure, heart rate, echocardiographic parameters,
exercise duration, laboratory data and quality of life were measured. After a 2
week run-in period starting daily dose of study drug was 5 mg, and an increase of
medication was considered at 4 weeks. At the end of the study mean daily dose of
lisinopril was 15.1 +/- 6.2 mg. Improvement of NYHA status by 2 grades was
observed in 4 cases (9%), by 1 grade in 24 cases (51%), there was no change in 17
cases (38%), and worsening was observed in 1 case (2%). During the study both
systolic (p = 0.001) and diastolic blood pressure (p = 0.0006) decreased
significantly, the changes in pulse rate were not significant. Left ventricular
end systolic (p = 0.001) and end diastolic (p = 0.003) dimensions decreased,
ejection fraction rose by 4.4% (p = 0.0002). One patient was removed from the
study because of drug-induced cough. Comparison of all the laboratory data for
pre and post-study periods did not reveal any significant difference. Patients
treated with lisinopril improved significantly for clinical, haemodynamic,
echocardiographic and quality of life parameters, with few adverse experiences,
good tolerability and once-daily dose.
PMID- 11006712
TI - [22q11.2 chromosome deletion and velo-cardio-facial syndrome in a patient with
tetralogy of Fallot].
AB - Velo-cardio-facial syndrome includes the following clinical features: congenital
heart anomaly, velo-pharyngeal malformations and dysmorphic facial features. In
80% of the patients microdeletion of the long arm of chromosome 22 can be
detected. Many patients with DiGeorge syndrome have the same underlying
chromosomal etiology, however the same deletion results in severe dysmorphic
features, immune defect, hypocalcaemia and in severe mental retardation. In
isolated heart defects deletion can be detected in about 15% of the patients. We
report the detection of the microdeletion in a patient with tetralogy of Fallot,
minimal dysmorphic facial features and normal psychomotor development. Early
diagnosis of 22q11.2 chromosomal deletion is important for genetic counseling and
further rehabilitation. We emphasize the importance of genetic screening in
patients with isolated congenital heart defects.
PMID- 11006713
TI - [Anniversary of the first brain tumor removal in Hungary -- remembering Mor
Lipscher].
PMID- 11006714
TI - [Remembering a medical historian, Ferenc Kolos Mayer, on his birth centennial].
PMID- 11006716
TI - [Ethical problems of continuing medical education and self-education].
PMID- 11006717
TI - [Hungarian medical writings -- Castleman disease].
PMID- 11006715
TI - [Treatment of laryngeal constriction. By Professor Mihaly Groszmann of Vienna,
1875].
PMID- 11006718
TI - Does the type of judgement required modulate cue competition?
AB - According to the comparator process hypothesis (Matute, Arcediano, & Miller,
1996), cue competition in the learning of between-events relationships arises if
the judgement required involves a comparison between the probability of the
outcome given the target cue and the probability of the outcome given the
competing cue. Alternatively, other associative accounts (the Rescorla-Wagner
model: Rescorla & Wagner, 1972) conceive cue competition as a learning deficit
affecting the target cue-outcome association. Consequently, the comparator
process hypothesis predicts that cue competition occurs in inference judgements
but not in contiguity ones, for only the first type of judgement implicitly
involves such a comparison. On the other hand, the Rescorla-Wagner model predicts
cue competition in both inference and contiguity judgements, because it
establishes no relevant role for the type of judgement in producing cue
competition. In Experiments 1 and 2 we manipulated the relative validity of cues
and the type of question (inference vs. contiguity) in a predictive learning
task. In both experiments we found a cue competition effect, but no interaction
between the relative validity of cues and the type of question, suggesting that
the Rescorla-Wagner theory suffices to explain cue competition.
PMID- 11006719
TI - Stimulus representations in human Pavlovian conditioning: implications of missing
negative transfer across response systems.
AB - Three Pavlovian conditioning experiments with human participants are reported,
which investigated whether common or separate stimulus representations are
involved in solving nonlinear discrimination tasks in different response systems.
In our experiments we made use of a negative transfer effect between positive and
negative patterning. Experiment 1 specified the conditions under which such a
negative transfer effect occurs in human eyelid conditioning. Experiments 2 and 3
investigated whether a similar effect also occurs if two response systems--the
eyelid and the skin conductance response system--are trained with trials of both
types being randomly interleaved. The presence or absence of a negative transfer
effect indicates whether or not the stimulus representations involved in the two
conditioning processes overlap. The findings are discussed within the framework
of a neuropsychological model of hippocampal function. The results suggest that
the representations are distinct and thus support the idea of acquired
equivalence and distinctiveness of stimulus representations.
PMID- 11006720
TI - Rapid visual learning in the rat: effects at the 5-HT1a receptor subtype.
AB - The 5-hydroxytryptamine1a (5-HT1a) receptor agonist 8-hydroxy-2-(di-n
propylamino) tetralin (8-OH-DPAT; 0.15 mg/kg) impaired rats' rapid visual
learning on a computerized maze. This treatment also increased decision time (DT)
but the learning impairment was not necessarily a side-effect of slower
responding because, in this task, responses made at long DT are more accurate
than those at short DT. The selective 5-HT1a receptor antagonist WAY-100635 (0.3
mg/kg) was itself without effect on accuracy, but was effective in reversing
effects of 8-OH-DPAT (on both accuracy and DT). Within problems (i.e., over the
40-60 trials of a single discrimination), performance was reduced by treatment
with 8-OH-DPAT at all stages of learning. We conclude that this effect is
mediated through the 5-HT1a receptor site (rather than through some other
serotonergic receptor site or non-specific mechanism) as it was reversible by
treatment with WAY-100635. Although it could still arise from behaviourally non
specific effects, the performance deficit finds its best account in terms of the
psychological processes necessary to visual learning. Its reversal with WAY
100635 offers support to the hypothesis that 5-HT1a receptor antagonists could
improve cognitive function, under conditions of pre-existing impairment due to
overactive serotonergic inhibition, as is thought to occur in Alzheimer's
disease.
PMID- 11006721
TI - Is the context specificity of latent inhibition a sufficient explanation of
learned irrelevance?
AB - In three experiments, rats were pre-exposed either to uncorrelated presentations
of a light and sucrose pellets (group CS/US) or to equivalent presentations of
the light and pellets in separate sessions (control). In Experiment 1, subsequent
conditioning to the light proceeded more slowly in group CS/US than in the
control group, whether this conditioning was excitatory, with the light
signalling the delivery of pellets, or inhibitory, with the light signalling
their absence. Bonardi and Hall (1996) have argued that this learned irrelevance
effect may be reducible to latent inhibition, which would be stronger in group
CS/US because they are both pre-exposed and conditioned to the CS in the presence
of traces of previous USs occurring in the same session. This analysis implies
that group CS/US should have conditioned more rapidly to the CS than controls on
the first trial of each session in Experiment 1, but this did not happen. It also
implies that the learned irrelevance effect should be reversed if conditioning
trials are given at a rate of one per day. Experiments 2 and 3 found no support
for this prediction. We conclude that learned irrelevance effects cannot always
be reduced to latent inhibition.
PMID- 11006722
TI - Common coding in symbolic matching tasks with humans: training with a common
consequence or antecedent.
AB - The present experiments explored the importance of training with a common
antecedent or consequence for common coding in symbolic matching-to-sample tasks
with human subjects using reversal and transfer tests. Experiment 1 assessed
common coding following training in many-to-one (MTO) and one-to-many (OTM)
symbolic matching-to-sample tasks by comparing learning of partial and total
reversals of these contingencies. Experiment 2 assessed common coding in MTO and
OTM tasks by comparing performances in transfer tests when the common coding
relations in the transfer phase were either consistent or inconsistent with those
present during initial training. Evidence for common coding in the MTO and OTM
discriminations was obtained in both experiments, although the amount of common
coding was greater in the MTO discrimination in Experiment 1. These data are
discussed in terms of associative mediational approaches to common coding
phenomena. It is suggested that a basic requirement of an associative theory is
that common coding should be more likely to occur when the stimuli are trained
with a common consequence than when they are trained with a common antecedent,
and that this requirement has been at least partly satisfied in the present
studies.
PMID- 11006723
TI - [Capital punishment].
PMID- 11006724
TI - [Challenges in forensic psychiatry].
PMID- 11006725
TI - [A votre sante!].
PMID- 11006726
TI - [Referral to a specialist].
PMID- 11006727
TI - [Should optometrists be able to refer patients to ophthalmologists?].
AB - BACKGROUND: Today optometrists in Norway can refer patients directly to
ophthalmologists. Our article evaluates the quality of this practice. MATERIALS
AND METHODS: 198 referrals from optometrists and 208 from general practitioners
were evaluated. RESULTS: We found the referrals to be relevant to the
ophthalmologist for nearly 95% in both groups. INTERPRETATION: The existing
practice in which optometrists can refer their patients directly to
ophthalmologists should be continued.
PMID- 11006728
TI - [Hidden motor dysfunctions in children with epilepsy].
AB - BACKGROUND: At the National Center for Epilepsy, many years of clinical
experience with children with difficult-to treat epilepsy has left the impression
that many of these children may have motor difficulties in addition to their
seizures. The aim of this prospective, uncontrolled study was to investigate if
this impression could be confirmed. MATERIAL AND METHODS: In 41 children with
"epilepsy only", i.e. without mental retardation or cerebral palsy, their motor
performance was evaluated by means of the ABC test (Movement Assessment Battery
for Children). RESULTS: More than half of the children had test results
consistent with motor difficulties. The motor problems were most pronounced among
those with MRI-detectable brain lesions and symptomatic localisation-related
epilepsy. Gender, type and number of antiepileptic drugs or seizure frequency did
not influence the test results. INTERPRETATION: Hidden motor dysfunctions, which
may be caused by the aetiology of the epilepsy, the epilepsy itself, or the
epilepsy treatment may easily be overlooked and may represent an extra burden for
the children both at school and in their leisure time. We recommend that motor
function should be tested in children with severe epilepsy as part of a
comprehensive multiprofessional evaluation. Those with poor motor performance
should be offered sensory motor stimulation.
PMID- 11006729
TI - [Exposure therapy for anxiety disorders in a psychiatric ward].
AB - Exposure treatment is efficient as a treatment for some anxiety disorders.
Briefly described, it consists in letting the patient expose himself to an
anxiety-inducing situation without running away from it. In the author's
experience, this mode of treatment is too seldom used. This article exemplifies
conditions in which this form of therapy can be useful. The method is easily
learnt by general practitioners. The article describes the treatment of five
patients with these psychiatric diagnoses: agoraphobia, social phobia, compulsive
disorder, and post-traumatic stress disorder.
PMID- 11006730
TI - [Torsion of the Fallopian tube causing acute abdominal pain in a young virgin
girl].
AB - BACKGROUND: Acute abdominal pain in female patients is a common condition often
involving a gynaecological examination in order to establish an aetiological
diagnosis. MATERIAL: The case of a 14-year-old girl with acute abdominal pain
caused by isolated torsion of the right tube is presented. The literature is
reviewed according to the discussion on whether an undiseased tube can undergo
torsion. Theories concerning the pathogenesis of torsion and the premises for
accepting the fallopian tube as previously undiseased, are presented. RESULTS AND
INTERPRETATION: On the background of these premises we conclude that our patient
might be the eighth case referred in the literature.
PMID- 11006731
TI - [Forensic psychiatric risk assessment is ethically defensible. The dangerousness
and risk of relapse are possible to judge with more precision than random
assessment].
PMID- 11006732
TI - [Water channels of the cell--aquaporins].
AB - BACKGROUND: Several mechanisms in the body regulate the water transport within
the cells up and down during physiological and pathological conditions. The
discovery of aquaporins, water channel proteins, has brought more insight into
and understanding of how water crosses plasma membranes within cells in body
tissue. MATERIAL AND METHODS: The functions of aquaporins are not fully
understood; this paper summarise current knowledge of various aquaporins.
RESULTS: Known aquaporins are discussed in relation to some physiological,
pathological and clinical conditions. INTERPRETATION: In the future, measurements
of aquaporin concentrations in urine and possibly in other samples will give us a
broader picture of water exchange and a better understanding of the mechanisms
underlying water production in clinical states like renal and heart failure and
liver insufficiency. Moreover, by manipulating water channel proteins by
compounds developed for this purpose, one may have a tool for treating some
clinical disorders in which water depletion or water overload is an important
factor.
PMID- 11006733
TI - [Drug therapy of patients with emotionally unstable personality].
AB - BACKGROUND: Most patients with borderline personality disorders are treated with
psychotropic medication. There are, however, no clear clinical guidelines
concerning optimal treatment of the disorder. MATERIAL AND METHODS: This article
reviews the data on the efficacy of treatment with different classes of
psychopharmacological drugs. The emphasis is on clinical trials published after
1981, as most placebo-controlled double-blind studies have been done in the last
two decades. Furthermore, studies conducted before 1980 are more difficult to
interpret because of changes in clinical diagnostic criteria. RESULTS:
Neuroleptics have been studied most extensively followed by antidepressants.
Neuroleptics have a modest, but broad therapeutic effect on symptoms in all
domains. Doses are lower than those used for treating schizophrenia.
Antidepressants have a more inconsistent effect. Tricyclics have been the least
successful, whereas irreversible MAO inhibitors and selective serotonin reuptake
inhibitors (SSRIs) have been effective in treating mood symptoms and impulsivity.
Lithium has a possible effect in diminishing anger and suicidal symptoms.
INTERPRETATION: As there is no "drug of choice" for the treatment of borderline
personality disorder, a more rational clinical approach might be to treat
different symptom clusters (cognitive/schizotypal, affective, impulsive) rather
than the disorder itself. Finally, some practical guidelines for drug treatment
of the disorder are proposed.
PMID- 11006734
TI - [Relapse as quality indicator in psychiatric treatment].
AB - BACKGROUND: Efficiency and productivity expressed by length of hospitalisation,
number of admissions, treated patients per time unit, and cost in NOK are
incomplete measures for quality in a medical context. These measures should be
supplemented by measures of results based on the course of illness for specific
diagnostic categories. Few psychiatric institutions, including outpatient units,
record the course of illness on a regular basis. MATERIAL AND METHODS: A review
of the literature shows that rough measures of results, for instance readmission
rates, often form the basis for evaluation of course/treatment results. The
article gives examples of measures like readmission rates and more scientific
measures such as Positive and negative syndrome scale (PANSS) used to measure
results in a Norwegian psychiatric hospital. RESULTS: Of all first time admitted
patients to Rogaland Psychiatric Hospital in 1985 and 1990, 40% of patients
diagnosed with schizophrenia were readmitted after one year. For first time
admitted patients from 1993 and 1994, the remission rate was 56% measured by
PANSS. INTERPRETATION: The results of the treatment of first time admitted
patients with a schizophrenia diagnosis were poorer than what is suggested
possible through studies of optimal treatment, where the remission percentage is
estimated to be 80% after one year. Rough measures of results, like readmission,
do not seem to differ considerably from the results measured by PANSS. Norwegian
psychiatric institutes are recommended to monitor the quality of treatment
through a systematic recording of relapse among patients with a first time
schizophrenia diagnosis.
PMID- 11006735
TI - [Driving under the influence of medication and various substances other than
alcohol].
PMID- 11006736
TI - [Screening for psychiatric disorders among prison inmates].
AB - BACKGROUND: Prison inmates have high frequencies of psychiatric disorders. Most
prisons have little health-personnel resources, and methods to help focus
resources towards those with serious health-care needs would be useful. The
Global Symptom Index (GSI) of the Symptom Check List-90 (SCL-90) has performed
well in other populations. MATERIAL AND METHODS: Prisoners at Kristiansand County
Prison, Norway were asked to participate in the study, and 187 of 206 (91%)
consented. All filled in the SCL-90 during the first four days of incarceration,
and were examined clinically by a psychiatrist. RESULTS: Clinical examination
revealed 40 persons with psychiatric disorder. Of these, 37 had a GSI score > or
= 1. There were three false negatives and two false positives. Based on various
cut-off levels for the GSI, we found a GSI cut-off value at 1.5 to perform best
with sensitivity = 0.78, specificity = 0.87, and Number Needed to Diagnose =
1.55. INTERPRETATION: SCL-90 performs well as a screening instrument for
psychiatric disorders among prison inmates.
PMID- 11006737
TI - [Freedom as a medical problem--forensic psychiatry in a philosophical
perspective].
PMID- 11006738
TI - [Preventive detention or custody--reflections over the new legal reactions].
PMID- 11006739
TI - [Serving a sentence on medical basis].
PMID- 11006740
TI - [Telemedicine--organizational consequences more than just talk?].
AB - In the telemedicine community, the possibility of organisational consequences of
the technology have been mentioned frequently. But little has been published on
the subject. We may speak of five categories of application of the new
technology: clinical use, medical service functions, extramural applications,
skills enhancement; and management and administration. Organisational
consequences may be of four types: changes in distribution of tasks between
levels of care and between organisations at the same levels, new division of work
and change in skills; groups of individuals who are not co-located may co-operate
in problem-solving, and the technology may become a tool of co-ordination for
organisations. Empirical studies of the impact on organisation are few, but a
Norwegian study confirmed that telemedicine already has such impact on the health
service.
PMID- 11006741
TI - [Telepathology at the Norwegian Radium Hospital].
AB - BACKGROUND: The article gives an overview of the telepathology activity at the
Norwegian Radium Hospital from the service was launched in 1994 and up until
today. We show the development during these years and discuss telepathology in
general terms. We also discuss those aspects that determine how well a
telepathology service functions. MATERIAL AND METHODS: 74 frozen section slides
were diagnosed by two different telepathology systems. One of these systems was
used for examining its appropriateness as a tool for second opinion in pathology.
A new Internet-based system was developed that provided additional functionality.
RESULTS: A telepathology system with a digital camera outperforms one with an
analog camera with respect to diagnostic accuracy. INTERPRETATION: Image quality
determines the precision of a telepathology service. Telepathology is a feasible
tool for second opinion in pathology.
PMID- 11006742
TI - [Telemedicine as means to recruit physicians to the districts].
PMID- 11006743
TI - [Stigma and stigmatization in psychiatry--a field which requires achievements?].
PMID- 11006744
TI - [European survey at the Center of Child and Adolescent Psychiatry].
PMID- 11006745
TI - [Hemovigilance--a new name or an old, unfulfilled need].
PMID- 11006746
TI - [Ovarian cancer screening of high risk groups].
PMID- 11006747
TI - [Unnuanced on cancer risk using snuff].
PMID- 11006748
TI - [Cardiologic procedures at a smaller Norwegian hospital--educational potential
for assistant residents].
PMID- 11006749
TI - [New diagnostic criteria for diabetes mellitus].
PMID- 11006750
TI - [About the diagnostics of obturator hernia].
PMID- 11006751
TI - [Practice from Germany not sanctioned as specialist education in Norway].
PMID- 11006752
TI - [Latin in Norway and the Nordic countries].
PMID- 11006754
TI - Ecosystem evasion and health.
PMID- 11006753
TI - [Pain relief and euthanasia].
PMID- 11006755
TI - A step toward putting a genie back in its bottle.
PMID- 11006756
TI - Research ethics and a patient in her 70s.
PMID- 11006757
TI - Jehovah's Witnesses and artificial blood.
PMID- 11006758
TI - Comparing international infant mortality rates.
PMID- 11006759
TI - The last trial of a Nazi doctor.
PMID- 11006760
TI - Prevalence and predictors of human papillomavirus infection in women in Ontario,
Canada. Survey of HPV in Ontario Women (SHOW) Group.
AB - BACKGROUND: Human papillomavirus (HPV) is thought to be the primary cause of
cervical intraepithelial neoplasia and cervical cancer. We determined the age
specific prevalence of HPV infection and its risk factors in Ontario women.
METHODS: We obtained 2 cervical specimens from randomly selected women (in 5-year
age categories, from 15 to 49 years) who were being seen in 32 family practices
for cytologic screening. The specimens were tested for carcinogenic HPV by the
hybrid capture II assay (Digene Corp., Silver Spring, Md.) and by polymerase
chain reaction (PCR) and genotyping. RESULTS: Of 1004 women eligible to
participate, samples were obtained from 955 (95.1%). The prevalence of HPV (as
determined by the hybrid capture II method) was highest, at 24.0% (95% confidence
interval [CI] 16.5% to 31.5%), among women 20 to 24 years of age and was
progressively lower in older age groups, reaching 3.4% (95% CI 0.1% to 6.7%) in
women 45 to 49 years old. The prevalence of HPV (any type) as determined by PCR
showed a similar pattern but was significantly higher (p = 0.01) among women 45
to 49 years old than among those 40 to 44 years old (13.0% [95% CI 6.4% to 19.6%]
v. 3.3% [95% CI 0.1% to 6.5%]). Risk factors for positivity with the hybrid
capture II method were never-married status, divorced or separated status, more
than 3 lifetime partners, more than 1 partner in the preceding year, cigarette
smoking and current use of oral contraceptives. The presence of squamous
intraepithelial lesions on cytologic examination was strongly associated with
positivity with the hybrid capture II assay (odds ratio 96.0, 95% CI 22.3 to
413.4; p < 0.01). INTERPRETATION: The highest prevalence of HPV was 24.0%, in
women 20 to 24 years old. Risk factors supported a sexual mode of transmission,
and there was a strong association between HPV and abnormal cervical cytologic
results.
PMID- 11006761
TI - Comparison of self-collected vaginal, vulvar and urine samples with physician
collected cervical samples for human papillomavirus testing to detect high-grade
squamous intraepithelial lesions.
AB - BACKGROUND: Certain types of human papillomavirus (HPV) in cervical samples are
strongly associated with squamous intraepithelial lesions (SIL) and invasive
cervical carcinoma. We determined and compared the test characteristics of
testing for HPV with samples obtained by patients and with samples obtained by
their physicians. METHODS: In a consecutive series of women referred to a
colposcopy clinic at a teaching hospital because of abnormalities on cervical
cytologic screening, 200 agreed to collect vulvar, vaginal and urine samples for
HPV testing. The physician then collected cervical samples for HPV testing, and
colposcopy, with biopsy as indicated, was performed. Presence of HPV was
evaluated using the hybrid capture II assay (Digene Corp., Silver Spring, Md.)
with a probe cocktail for 13 carcinogenic types. Cervical specimens were also
tested for HPV by polymerase chain reaction and hybridization with type-specific
probes. Cervical smears for cytologic examination were obtained from all women.
RESULTS: High-grade lesions (high-grade squamous intraepithelial lesions [HSIL],
equivalent to cervical intraepithelial neoplasia [CIN] grade 2 or 3, and
adenocarcinoma) were found in 58 (29.0%) of the 200 women. Carcinogenic types of
HPV were detected in the self-collected vaginal samples of 50 (86.2%) of these 58
women, in the self-collected vulvar samples of 36 (62.1%) and in the self
collected urine samples of 26 (44.8%). Carcinogenic types of HPV were detected in
the cervical samples collected by physicians for 57 (98.3%) of these 58 women.
The remaining 142 women (71.0%) had normal findings or low-grade squamous
intraepithelial lesions (LSIL, CIN grade 1). Test results were negative or
noncarcinogenic types of HPV were detected in the self-collected vaginal samples
of 76 (53.5%) of these 142 women, in the self-collected vulvar samples of 89
(62.7%) and in the self-collected urine samples of 99 (69.7%). The sensitivity
for self-collected samples ranged from 44.8% to 86.2%, and the specificity from
53.5% to 69.7%. For the samples collected by physicians, the sensitivity was
98.3% and the specificity 52.1%. The self-sampling methods were generally
acceptable to the women: 98.4% of respondents (126/128) deemed urine sampling
acceptable, 92.9% (118/127) found vulvar sampling acceptable, and 88.2% (112/127)
found vaginal sampling acceptable. INTERPRETATION: Self-collection of samples for
HPV testing was acceptable to women attending a colposcopy clinic for
investigation of suspected cervical lesions and shows sufficient sensitivity to
warrant further evaluation as a screening test for cervical cancer prevention
programs.
PMID- 11006762
TI - Evaluating the benefits of antimicrobial prophylaxis to prevent urinary tract
infections in children: a systematic review.
AB - BACKGROUND: The recurrence rate for urinary tract infections in children is
estimated at between 30% and 40%. The use of low doses of antibiotics as
prophylaxis for recurrent urinary tract infections is common clinical practice.
However, prolonged antimicrobial therapy has the potential to contribute to
problems of bacterial resistance and antimicrobial side effects. The aim of this
review was to systematically examine the available evidence for the effectiveness
of this intervention. METHODS: We conducted a literature search of 3 electronic
databases for the period 1966 to 1999. We also searched bibliographies from
conference proceedings and contacted content experts to ensure completeness of
our database. Each trial was evaluated on the basis of the following inclusion
criteria: target population (children), intervention (antibiotic v. no
antibiotic), outcome (number of urinary tract infections) and study design
(randomized controlled trial). Quality was assessed for the studies that met
these criteria. RESULTS: Most of the studies identified were case series and
cohort studies. Only 6 randomized trials fulfilled the inclusion criteria. All
were of low quality (median 2, range 0 to 2 [maximum quality score 5]). Three
trials dealt with children who had anatomically normal urinary tracts, and three
included children with neurogenic bladder. The rate of infections for patients
with normal urinary tracts ranged from 0 to 4.0 per 10 patient-years for the
treatment groups and from 4.0 to 16.7 for the control groups. The recurrence
rates for patients with neurogenic bladders in 2 trials were 2.9 and 17.1 per 10
patient-years for the treatment groups and 1.5 and 33.0 for the control groups.
INTERPRETATION: The available evidence for using antimicrobial prophylaxis to
prevent urinary tract infection in children with normal urinary tracts or
neurogenic bladder is of low quality. This suggests that the magnitude of any
benefit should at best be questioned. The surprising lack of data for children
with reflux is of concern. Well-designed trials are needed to optimize the use of
antimicrobials in children with recurrent urinary tract infection.
PMID- 11006763
TI - Environment and health: an overview.
PMID- 11006764
TI - Screening for cervical cancer: should we test for infection with high-risk HPV?
PMID- 11006765
TI - Colorectal cancer screening: now is the time.
PMID- 11006766
TI - Population-based fecal occult blood screening for colon cancer: will the benefits
outweigh the harm?
PMID- 11006767
TI - Environment and health: 1. Population, consumption and human health.
PMID- 11006769
TI - Postoperative tetanus: a case report.
PMID- 11006768
TI - Type 2 diabetes mellitus in Canada's first nations: status of an epidemic in
progress.
AB - This review provides a status report on the epidemic of type 2 diabetes mellitus
that is affecting many of Canada's First Nations. We focus on the published
literature, especially reports published in the past 2 decades, and incorporate
data from the Aboriginal Peoples Survey and the First Nations and Inuit Regional
Health Survey. We look at the extent and magnitude of the problem, the causes and
risk factors, primary prevention and screening, clinical care and education, and
cultural concepts and traditional knowledge. The epidemic of type 2 diabetes is
still on the upswing, with a trend toward earlier age at onset. Genetic
environmental interactions are the likely cause. Scattered intervention projects
have been implemented and evaluated, and some show promise. The current health
and social repercussions of the disease are considerable, and the long-term
outlook remains guarded. A national Aboriginal diabetes strategy is urgently
needed.
PMID- 11006770
TI - FDA considering restricted access to "abortion pill".
PMID- 11006771
TI - More net-savvy MDs surfing the Web.
PMID- 11006772
TI - MDs get jail terms, fines as new police squad targets health fraud.
PMID- 11006773
TI - RNs seek broader prescribing powers in quest for more autonomy.
PMID- 11006774
TI - COX-2 inhibitors and renal function in elderly people.
PMID- 11006775
TI - Utility of the clinical examination for carpal tunnel syndrome.
PMID- 11006776
TI - Anthrax: of bison and bioterrorism.
PMID- 11006777
TI - Benchmarking: a prescription for healthcare.
PMID- 11006778
TI - Assurance services and healthcare.
PMID- 11006779
TI - The nursing shortage. A difficult conversation.
PMID- 11006780
TI - Is now the time to design new care delivery models?
PMID- 11006781
TI - Linking practice and education.
PMID- 11006782
TI - Nursing administrative practicum. Enhancing communication between staff nurses
and nursing leadership.
PMID- 11006783
TI - Organizational trust and empowerment in restructured healthcare settings. Effects
on staff nurse commitment.
AB - In today's dramatically restructured healthcare work environments, organizational
trust is an increasingly important element in determining employee performance
and commitment to the organization. The authors used Kanter's model of workplace
empowerment to examine the effects of organizational trust and empowerment on two
types of organizational commitment. A predictive, nonexperimental design was used
to test Kanter's theory in a random sample of 412 Canadian staff nurses.
Empowered nurses reported higher levels of organizational trust, which in turn
resulted in higher levels of affective commitment. However, empowerment did not
predict continuance commitment--that is, commitment to stay in the organization
based on perceived lack of other job opportunities. Because past research has
linked affective commitment to employee productivity, these results suggest that
fostering environments that enhance perceptions of empowerment and organizational
trust will have positive effects on organizational members and increase
organizational effectiveness.
PMID- 11006784
TI - Building community in the healthcare workplace. Part 2, Envisioning the reality.
AB - Squeezed between mounting budget pressures and staffing demands, healthcare
managers have little room to maneuver as they are buffeted by incessant new
strategies. So what is the constant that they can use to keep a steady course
through all the chaos? We suggest that the overarching constant is "community in
the workplace." Although community building may have both short- and long-term
benefits, it is not a strategy but a career-long philosophy, structure, and
approach to help managers tie together all the facets of their daily work into a
more meaningful and satisfying purpose. This article, part 2 in a 4-part series,
explores the principles and characteristics of community and provides material
for further study and discussion. Four conceptual cornerstones--philosophy,
influence, culture, and inner transformation--are considered in relation to the
community approach. Part 1 (April) described the negative dynamics that obstruct
sustainable change and reasons for moving to community at work. Part 3 (October)
will describe how to build community and will give options for implementing
change in complex adaptive systems. The final article (November) presents case
studies and discusses how community can be built in a unionized environment.
PMID- 11006785
TI - Skills needed for promotion in the nursing profession.
AB - OBJECTIVE: This research was designed to identify skills (interpersonal versus
technical) important to promotion within the nursing profession. Also studied was
the difference between actual and perceived importance of the skills. BACKGROUND:
For many technical and academic professions, career advancement is attained
through promotions. These promotions often take one further away from the front
line; thus, the technical skills so important in one's early career become less
important. Interpersonal skills, on the other hand, increase in importance when
one is supervising other professionals. Though research has described this
phenomenon, it is not known exactly where the shift in importance occurs or what
the precise nature of the shift may be. Further research in this area is
particularly important to management development programs in technical,
scientific professions. METHODS: A policy-capturing approach was used to identify
the skills important to managerial advancement in the nursing profession. Two
hundred nineteen nurse administrators from a large Southeastern United States
hospital rated hypothetical candidates for managerial positions. At the lowest
level management position studied, a greater number of technical skills
significantly influenced promotion decisions than at middle management.
Significant differences were found between decision-makers' perceptions of skill
importance and the skills' actual importance to promotion decisions. RESULTS: The
present research indicate that a greater number of technical skills are important
for promotion to CN3 than for promotion to ANM. The results also suggest decision
makers are not always 100% accurate in their insight regarding the specific
factors influencing their personnel decisions.
PMID- 11006786
TI - Development of a nursing management practice atlas. Part 2, Variation in use of
nursing and financial resources.
AB - Developing mechanisms for making benchmark comparisons among hospital
organization is a challenge that has been embraced by nurse executives. A
methodologic approach for ensuring data congruency when using available secondary
data bases for making benchmark comparisons was detailed in part one
(July/August) of this two-part series. This second article analyzes nursing
management data using a set of nursing and financial resource variables
identified by senior nurse executives of the hospital sites involved in this
study.
PMID- 11006788
TI - Treatment of diffuse parenchymal lung disease. Part 2.
PMID- 11006789
TI - Tinzaparin is newest entry into low-molecular-weight heparin market.
PMID- 11006790
TI - Argatroban approved for heparin-induced thrombocytopenia.
PMID- 11006791
TI - Iowa Medicaid to begin paying pharmacists in case management project.
PMID- 11006792
TI - Better outcomes, higher costs associated with patient-centered hospital units.
PMID- 11006787
TI - The diagnosis, assessment and treatment of diffuse parenchymal lung disease in
adults. Introduction.
PMID- 11006793
TI - Analysis finds modest effect for antimicrobials in acute otitis media.
PMID- 11006794
TI - Pharmacy technician's role in an ambulatory care infusion clinic.
PMID- 11006796
TI - Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced
emesis.
AB - The theoretical basis for and clinical experience with using oral serotonin type
3 (5-HT3)-receptor antagonists for preventing chemotherapy-induced emesis are
discussed. Evidence supports the idea that antineoplastic drugs and irradiation
can initiate emesis by releasing serotonin from enterochromaffin cells in the gut
mucosa, which activates peripheral vagal afferent nerves. In view of the GI site
of serotonin release and vagal afferent activation, the proximity of neuronal 5
HT3 receptors, and the pharmacologic properties of 5-HT3-receptor antagonists,
the oral use of these agents is rational. Oral granisetron 2 mg once daily or 1
mg twice daily has been evaluated in more than 4500 patients receiving highly or
moderately emetogenic chemotherapy. Rates of total control of emesis ranged from
44% to 60%, and complete-response rates ranged from 70% to 94%. Oral ondansetron
8 mg three times daily has proven effective in patients receiving antineoplastics
with moderate or moderately high emetogenic potential. Two double-blind studies
demonstrated the efficacy of a single 24-mg oral dose of ondansetron administered
approximately 30 minutes before cisplatin-based chemotherapy. Patients randomized
to oral ondansetron had higher total-control and complete-response rates than
patients receiving intravenous granisetron or ondansetron. Oral dolasetron 100 or
200 mg once daily also prevented emesis. Oral administration of 5-HT3-receptor
antagonists for the prevention of acute emesis associated with chemotherapy is
rational and appears to be effective.
PMID- 11006795
TI - Raloxifene hydrochloride.
AB - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and
therapeutic role of raloxifene hydrochloride are reviewed. Raloxifene is a
selective estrogen-receptor modulator (SERM) that has been approved for use in
the prevention and treatment of osteoporosis in postmenopausal women. A SERM
interacts with estrogen receptors, functioning as an agonist in some tissues and
an antagonist in other tissues. Because of their unique pharmacologic properties,
these agents can achieve the desired effects of estrogen without the possible
stimulatory effects on the breasts or uterus. Raloxifene is rapidly absorbed from
the gastrointestinal tract and undergoes extensive first-pass glucuronidation.
Approximately 60% of a dose is absorbed; however, absolute bioavailability is
only 2%. The volume of distribution is 2348 L/kg for a single oral dose of 30-150
mg, and the elimination half-life averages 32.5 hours. In clinical trials in
postmenopausal women, raloxifene had an estrogen-like effect on bone turnover and
increased bone mineral density. It reduced the risk of fractures in women with
osteoporosis. Raloxifene also seemed to reduce the risk of breast cancer and
positively influenced blood lipid markers of cardiovascular disease. Raloxifene
is generally well tolerated; the most common adverse effects are hot flashes and
leg cramps. A serious adverse effect is venous thromboembolism. The recommended
dosage is 60 mg/day orally without regard to meals. Ultimately, it will be
information on cardiovascular or breast cancer benefits that will determine the
future role of raloxifene. Raloxifene is an alternative to traditional hormone
replacement therapy for the prevention and treatment of osteoporosis in selected
postmenopausal women. More study is needed to verify possible benefits related to
heart disease and breast cancer.
PMID- 11006797
TI - Comparison of three a priori methods and one empirical method in predicting
lithium dosage requirements.
AB - The precision and bias of three a priori methods and an empirical method for
predicting lithium dosage requirements were studied. Data on serum lithium
concentrations were collected from inpatient medical records at a state
psychiatric hospital. Predicted daily lithium doses were calculated by using a
priori methods proposed by Zetin et al., Jermain et al. and Pepin et al., and an
empirical method and compared with the patients' actual dosages. Similar
comparisons were made with respect to serum lithium concentrations at steady
state. Absolute mean error and mean error were calculated to assess the precision
and bias of each a priori method. The records of 47 patients were used in the
study. Average mean error for dosage predictions was -130.41, -187.69, 170.80,
and -357.23 mg/day for the Jermain, Pepin, Zetin, and empirical methods,
respectively. Average mean error for serum lithium concentration predictions was
0.11, -0.09, and 0.37 meq/L for the Jermain, Pepin, and empirical methods,
respectively. The Jermain and empirical methods significantly overpredicted
concentration and underpredicted dosage. The Zetin method overpredicted dosage.
The Pepin method underpredicted dosage but not concentration. The average
difference in dosage error among the methods was only 73.3 mg/day. Three a priori
dosing methods were similar to an empirical method in their ability to predict
lithium dosages. All methods were biased. Although all a priori methods were more
precise than the empirical method, the clinical significance is unclear.
PMID- 11006798
TI - Conversion of patients from simvastatin to lovastatin in an outpatient pharmacy
clinic.
PMID- 11006799
TI - Variations in finishing time of 24-hour chemotherapy infusions.
PMID- 11006800
TI - Thinking out of the box.
PMID- 11006801
TI - Costs and bacterial susceptibility after therapeutic interchange of
fluoroquinolones.
PMID- 11006802
TI - Cost of cerivastatin in cost-effectiveness study.
PMID- 11006803
TI - Muscle relaxants and renal failure.
PMID- 11006804
TI - Under renovation: incorporating change.
PMID- 11006805
TI - Evolving narratives in the course of retirement: a longitudinal study.
AB - This paper presents results from the second phase of a longitudinal study of
retirement. Data were gathered through interviews with 29 participants (65 to 66
years of age) who had previously been interviewed when they were 63 to 64 years
of age and still working. Data were analyzed by characterizing each subject's
narrative about retirement in terms of its narrative slope--progressive,
stability, or regressive. These current narratives also were compared with the
earlier narratives these participants told. It was found that, while anticipatory
narratives may predispose persons toward action, they are not so much a fixed
"script for action" as an orientation to act within circumstances. While
participants' narratives anticipating retirement often turned out as expected,
they were sometimes reshaped as a consequence of personal action, external
events, and unexpected experiences within new retirement occupations. The study
suggests that, while narratives play a role in shaping the direction of persons
lives, they also interweave with and change directions as a result of ongoing
life events and experiences.
PMID- 11006806
TI - The predictive power of narrative data in occupational therapy evaluation.
AB - OBJECTIVE: This study examined whether adding the Canadian Occupational
Performance Measure (COPM) to existing occupational therapy evaluation measures
used in a subacute skilled nursing facility unit enhanced the accuracy of
therapists' predictions of the functional status of clients at discharge. METHOD:
This study utilized a prospective comparison design. Two independent predictive
variables were developed using the standard Functional Independent Measure (FIM),
and an enhanced FIM that included narrative information from the Canadian
Occupational Performance Measure (FIM/COPM). These variables were subsequently
compared with the actual FIM discharge (DFIM) scores for 31 clients. The primary
author (D.S.) gathered data from chart review and conducted the statistical
analysis. The data were analyzed using descriptive correlations (Pearson r) and
comparison statistics (Wilcoxon signed rank test). RESULTS: Comparison statistics
(Wilcoxon signed rank test) revealed a statistically significant difference
between the standard FIM predictive score and the discharge FIM score. No
statistically significant difference was found between the FIM/COPM predictive
score and the discharge FIM score. These findings suggest that predictive scores
based solely on information attained from the standard FIM resulted in less
accuracy in outcome predictions. Correlational analyses further supported these
conclusions. CONCLUSION: The findings support the study hypothesis that use of
the COPM in combination with the FIM enhances accuracy in prediction of outcomes
for rehabilitative services for persons in adult physical disabilities settings.
PMID- 11006807
TI - The effects of hands-on occupation versus demonstration on children's recall
memory.
AB - OBJECTIVE: Hands-on learning has been an important aspect of the profession of
occupational therapy since its founding. The purpose of this study was to
determine whether children engaged in hands-on learning would be able to recall
more of the steps and more of the correct order of the steps of an occupation
than children engaged in a demonstration teaching method. METHOD: After being
randomly assigned, 73 healthy third-graders (42 girls and 31 boys) either
participated in making a model of a volcano or observed the making of a model of
a volcano. Following task completion, both groups were asked to recall and state
as many of the 41 syntactical units as possible in their proper order. The
children's responses were audiotaped and scored in a blind fashion according to
predetermined criteria. Interrater reliability was excellent. RESULTS: A t-test
revealed a significant difference between conditions in terms of free recall
scores, with children in the hands-on condition having a greater recall score, t
(71) = 2.63, p < .005. The effect size d equaled .62. A MannWhitney U Test
revealed no significant difference between conditions in terms of remembering the
steps in proper order (the lack of a significant difference may have been due to
a problem of measurement). CONCLUSION: The results of this study demonstrated
that participants were able to recall more information when engaged in a hands-on
teaching method as compared with a demonstration method. It is suggested that the
learning advantages of hands-on occupation are related to the enhanced
sensory/perceptual experiences and the feelings of success that are
characteristic of hands-on learning, as opposed to passive forms of learning.
PMID- 11006808
TI - Reliability and validity of a parent questionnaire on childhood motor skills.
AB - OBJECTIVE: As the consequences of clumsiness in children become better
understood, the need for valid measurement tools is apparent. Parent report has
the potential for providing historical knowledge of the child's motor skills, as
well as perceptions of their children's motor difficulties. The objective was to
develop a parent questionnaire to identify motor difficulties in children.
METHOD: A sample of 306 children participated in the development of a 17-item
parent questionnaire, called the Developmental Coordination Disorder
Questionnaire (DCDQ). Internal consistency, concurrent and construct validity
were examined. RESULTS: The DCDQ proved capable of distinguishing children who
had motor problems (as measured by standardized tests) from children without
motor problems. Correlations with standardized tests were significant. Two other
studies confirmed the construct validity of the DCDQ. Factor analysis revealed
four distinct factors, useful in defining the nature of the difficulties.
CONCLUSION: The DCDQ is a succinct and useful measure for use by occupational
therapists.
PMID- 11006809
TI - The evaluation of sensory processing: a validity study using contrasting groups.
AB - The purpose of this study was to examine the validity of a sensory history
questionnaire using contrasting groups. Specifically, the goal was to identify
items on the Evaluation of Sensory Processing that differentiate between parent
ratings of children with sensory integrative dysfunction and parent ratings of
typically developing children. Data were collected from 30 parents of children
with sensory integrative dysfunction and 59 parents of typically developing
children. Items were analyzed using a Wilcoxon signed rank test to detect the
difference between the parent ratings for the 30 children with sensory
integrative dysfunction and 30 of the typically developing children who were
matched to the dysfunctional children on age, ethnicity, gender, geographic
location, and socioeconomic status. Eighty-four of the 200 items significantly (p
< .05) distinguished between parents' ratings of children with and without
sensory integrative dysfunction.
PMID- 11006810
TI - Relationship between choice and quality of life among residents in long-term-care
facilities.
AB - OBJECTIVE: This study tested the association between perceptions of personal
control and quality of life among older persons. METHOD: Two self-report
instruments. The Quality of Life Rating (QOLR) and the Duncan Choice Index (DCI),
were administered to 21 residents in a long-term-care facility. The DCI was
developed for this study to measure the amount of choice available in 29 self
care and leisure activities. RESULTS: A significant positive correlation (r =
.54; p = .01) between the amount of choice residents perceive they have and their
quality of life was found. The DCI was shown to be reliable with preliminary
evidence of construct validity. CONCLUSION: Enhancing personal control in
everyday life may be associated with improved quality of life. Occupational
therapy strategies to empower residents through increasing choice and control
include increasing community in the facility emphasizing personal responsibility,
and enabling choices in everyday tasks.
PMID- 11006811
TI - Role perceptions of occupational therapists providing support and education for
caregivers of persons with dementia.
AB - OBJECTIVE: This pilot study explored occupational therapists' perceptions of
their roles as interventionists providing education and support for caregivers of
persons with dementia. The intervention was provided in caregivers' homes as part
of a larger funded study. METHOD: Interviews were conducted with four
occupational therapists to elicit their reflections on practice and their views
on occupational therapy services on the basis of their experiences providing
support and education for caregivers in the funded study. RESULTS: Key themes
consisted of the contrasts between the therapists' roles in the study and their
customary practices and the professional and personal impact of their role in the
study. Their recommendations for occupational therapy services emphasized the
need to (a) collaborate with patients, families, and other health care staff
members to solve problems; (b) acknowledge others as experts; (c) include family
perspectives; and (d) fully address the needs of patients and families in their
home environments. CONCLUSION: Providing support and education for caregivers in
the community can be a major transition for therapists accustomed to practicing
in more traditional settings. Additional research is needed to explore the ways
in which specific practice contexts influence delivery of occupational therapy
services.
PMID- 11006812
TI - The Joint Protection Behavior Assessment: a reliability study.
AB - OBJECTIVE: Of the various measures developed for studying persons with rheumatoid
arthritis, only one that focuses on joint protection has undergone extensive
testing, the Joint Protection Behavior Assessment (JPBA). The purpose of the
present study was to examine the interrater and intrarater reliability of the
JPBA. METHOD: Six healthy participants performed the JPBA under three test
conditions (uninformed, informed, completely guided joint protection behavior).
The 18 test performances were videotaped and scored by nine independent raters.
RESULTS: Analysis of these data showed that interrater reliability (intraclass
correlation coefficient [ICC]) was .90 or higher, and intrarater reliability was
.95 or higher (ICC). The correlation between the JPBA and its two shortened
versions was .95 or higher (ICC). Internal consistency was also high, with a
coefficient alpha of 0.95 for the complete JPBA. Kappa values showed that for
most subtasks, there was fair to excellent agreement between raters and
consistency of raters over time. CONCLUSION: Our data suggest that the complete
JPBA has excellent clinimetric properties and that the shortened versions are
adequate for clinical situations. Some improvements in the test manual suggested
by the present study may further improve the measure. A repeat of this study
under real-world circumstances would provide an estimate of JPBA reliability in
clinical practice.
PMID- 11006813
TI - Perceived risk as a constraint on occupational performance during hot and cold
water pouring.
AB - OBJECTIVE: Occupational therapists are interested in quality of movement under
different environmental conditions. It has been shown that during reaching tasks,
the physical aspects of the objects to be grasped can influence the quality of
movement. This study investigated whether perceived risk (water temperature)
affected the quality of movement during a pouring task. METHOD: In a
counterbalanced, repeated measures design, 56 participants (M = 27.1 years, SD =
7.4 years) poured hot, then cold water to prepare hot and cold beverages.
Dependent variables included movement time, displacement, peak velocity,
percentage of movement time to peak velocity, and movement units. Data were
analyzed with paired t tests. RESULTS: Participant performance in displacement
and movement time was significantly different when considering the entire pouring
task for both the hot and the cold conditions (ps < .05). In addition,
significant differences were found in the discrete movement "sub-portions" of the
pouring task (ps < .05). CONCLUSION: Perceived risk is an element of meaning that
the occupational therapist can consider in providing the person with just enough
challenge to facilitate successful performance. By varying the amount of
perceived risk in the occupational form, the therapist can help the person
experience and develop the range of movement strategies required by everyday
occupations. Future research is needed to corroborate these findings in simple
and more complex occupations as well as to examine perceived risk in special
populations.
PMID- 11006814
TI - Perspectives on faculty clinical practice: views of occupational therapy
curriculum chairpersons and faculty members.
AB - OBJECTIVE: This study investigated whether and how faculty clinical practice
(FCP) was being implemented in occupational therapy professional education
programs. METHOD: Chairpersons and faculty members from all accredited entry
level occupational therapy curricula in the United States were asked to complete
questionnaires about their involvement in FCP. The chairperson questionnaire
consisted of primarily closed-ended questions that addressed the organization of
faculty practice within their programs, whereas the faculty questionnaire was
primarily open-ended and addressed faculty members' individual involvement in FCP
as well as the perceived benefits and drawbacks. Responses were analyzed for 39
program chairpersons and 136 faculty members were analyzed. RESULTS: Twenty-five
chairperson respondents reported that their educational program had FCP, and 44
faculty respondents indicated involvement in FCP during the past year. FCP was
more prevalent in public-funded institutions and academic health centers. Faculty
members primarily engaged in FCP in order to stay current, enhance teaching, and
develop networks. They reported increased credibility with students as an
important benefit of clinical practice. The primary reasons faculty members did
not engage in clinical practice were insufficient time and institutional
policies. CONCLUSION: Although many faculty members in occupational therapy
education programs value clinical practice as a part of their educator role, it
is necessary to negotiate responsibilities and rewards to prevent role overload
and comply with institutional policies.
PMID- 11006815
TI - Can we improve outcomes research by expanding research methods?
AB - Therapeutic process occurs individually and in groups. The outcome of
intervention, however, is demonstrated through changes in client performance in
treatment sessions, that is, in individuals. Individual function, then, is both
the target of intervention and the measure of effectiveness of occupational
interventions. Reporting occupational therapy outcomes necessitates culling
functional performances of individuals to describe the overall outcomes of an
occupational therapy program (Johnson, 1996). In a summary report, a manager
might combine outcomes from inpatient and outpatient services to depict the
overall impact of occupational therapy services. For example, the manager might
conclude that clients receiving occupational therapy services have an 85% rate of
regaining independent living in the community. The challenge in reporting overall
outcome is to find ways to demonstrate more clear links between individual
treatment and function. Conclusions about groups of clients are often presented
in the form of baseline and discharge comparisons that are easy to summarize. But
relying on pre- and posttesting may deprive us of valuable information that can
be gained by session-based analyses. Although it might appear cumbersome to
examine individual session outcomes, collecting outcomes data is done informally
by every therapist and client at the end of a treatment session. We suggest that
this informal procedure become a formal part of outcomes research and a more
routine part of occupational interventions.
PMID- 11006816
TI - The use of nerve blocks in conjunction with occupational therapy for complex
regional pain syndrome type I.
PMID- 11006817
TI - Occupational therapy in early intervention: applying concepts from infant mental
health.
PMID- 11006818
TI - Test-retest reliability of the Purdue Pegboard Test.
PMID- 11006819
TI - Teaching evidence-based practice.
PMID- 11006820
TI - [Forensic medicine experiences with methadone substitution in the Geneva canton].
AB - Methadone treatment for heroin addiction has followed three distinct periods in
Geneva, Switzerland. The first period (1970-1979) corresponds to the beginning of
the heroin addiction epidemic. Treatment was restricted to detoxification and did
not succeed in reducing fatal overdoses. During the second period (1980-1989),
methadone maintenance program was favoured but access to this program was
limited. This period has brought a decrease of illegal heroin consumption and
criminality but not of fatal overdoses. Finally, during the third period (since
1990), legislation was changed to allow easier access to methadone maintenance
program. As a consequence there was a significant drop in lethal heroin overdoses
and in deaths attributed to HIV.
PMID- 11006821
TI - [Alcohol stove as a source of CO poisoning in a camper].
AB - Although the number of deaths from fatal CO poisoning has strongly declined since
the change from coal gas to natural gas, accidental and suicidal carbon monoxide
intoxications still have to be expected. In motor vehicles the exhaust gases from
the engine and a stationary heating are the major sources of intoxication. In
closed campers and caravans the operation of gas and spirit cooking stoves etc.
may also lead to an accumulation of carbon monoxide due to incomplete combustion.
PMID- 11006822
TI - [Similar skin lesions in victim and perpetrator caused by a knife with a serrated
blade].
AB - Reported in this paper is an attack of two adolescents on a man who was killed in
the fight, with several kitchen knives being used, including two with grooved and
wave-grooved blades. One of the offenders held the victim tight from behind and
was injured by his attacking accomplice++. A grid mark on the left side of the
victim's face and the left forearm of the second offender in the back supported
the assumption of a knife with simple wave profile. Skin lesions of finer
structure below the left ear and on the left forearm of the victim suggested
involvement of a smaller kitchen knife with groove-milled wave profile. Offender
victim position and course of offence were verified and confirmed by evaluation
of these specific findings.
PMID- 11006823
TI - [Fatal hunting injuries in North Rhine-Westphalia].
AB - The investigation covers 14 fatal hunting accidents which occurred in North Rhine
Westphalia in the last 23 years, among them 13 firearm fatalities. All the
accidents happened during the statutory hunting season reaching a peak in the
main small game season. 86% of the persons causing the accidents and 73% of the
victims were over 41 years and experienced hunters. 36% of the accidents were
caused by the victims themselves. The fatal gunshot injuries were inflicted by
rifle bullets in 7 cases (54%) and shotgun pellets in six cases (46%). No
accidents were due to shotgun slugs or handgun ammunition. The main factors
responsible for the fatalities were: covering the victim while swinging on the
game (31%), failure to discharge the firearm while descending from the raised
hide or transporting the weapon in vehicles (31%), mistaking the victim for game
(15%), failure to discharge the weapon during a hunting break or while pressing
down obstacles or careless handling of the weapon (23%). In no case was the
accident caused by a defective weapon or ammunition. In conclusion aspects of
preventing fatal hunting accidents are discussed.
PMID- 11006824
TI - [Postmortem dog bites after sexually motivated homicide with multiple stab wounds
-differential diagnostic aspects].
AB - The body of a 20-year-old woman that had undergone significant putrefaction was
found lying on the bed of her apartment in a supine position. The legs were
straddled and apart from a T-shirt, she was naked. The inner side of the right
thigh showed a circumscribed 20 cm x 40 cm defect exposing the underlying
muscles. The wound margin was ragged and superficial scratch-type abrasions were
found in the vicinity of the injury margin. The investigating police officers
classified the injuries to be caused postmortem by a crossbreed dog that was
inside the apartment. No other signs of external force were found on the body at
the death scene and due to the previous history of the deceased, a drug death was
assumed. Autopsy revealed 13 vital stab wounds in the neck and aspiration of
blood in the lungs as well as signs of manual strangulation. The observed
coincidence of injuries due to postmortem animal depredation and stab wounds,
although in different localization, can be regarded as a rare entity in the light
of the literature. The morphological appearance of traumatic injuries due to
other causes can be modified by the simultaneous presence of postmortem injuries
caused by animals and difficulties can arise concerning the differential
diagnosis especially under poor conditions (e.g. advanced putrefaction) at the
death scene.
PMID- 11006825
TI - [Distribution of morphine and morphine glucuronides in body tissue and fluids-
postmortem findings in brief survival].
AB - An intoxication following administration of morphine, tramadol and atracurium in
a suicide case is reported. The route of administration and the amount of the
particular drug were known from the investigation of the death scene and the
findings of the postmortem examination. Tramadol was present in the gastric
contents as well as in blood, liver, kidney and brain samples, whereas the drug
could not be detected in muscle. All body fluids and tissues investigated
contained morphine as well as its 3- and 6-glucuronides with the exception of
muscle tissue. The concentrations of morphine and its glucuronide metabolites
were determined by LC/MS following solid phase extraction. Interestingly, the
concentration of M6G in brain, liver and kidney were close to the concentration
of M3G in the particular tissue. This phenomenon might be explained by a
preferential hydrolysis of M3G or by a preferential formation of M6G postmortem.
Measurement of morphine and M6G in femoral blood and cerebrospinal fluid may be a
useful indicator in rapid deaths.
PMID- 11006826
TI - [Significance of mitochondrial DNA for forensic stain analysis, identification
and forensic lineage determination].
AB - DNA testing using conventional STR systems may produce insufficient results, if
the genomic DNA in the specimen is either highly degraded or the available
quantity is very small (e.g. skin particles, hair shafts or ancient bones). In
some of these cases the examination of mitochondrial DNA, which is present in
considerably larger copy numbers in the cytoplasm, is more successful than that
of nuclear DNA. Identification of unknown corpses by conventional DNA typing
sometimes remains doubtful, if only samples from presumably distant relatives or
putative brothers or sisters are available for comparison. Since mitochondrial
DNA is generally transmitted in maternal lineages, its sequence pattern can be
directly compared with those of other individuals and, in case of the same
maternal lineage, corresponding sequence chromatograms are to be expected. In
connection with nuclear DNA typing methods certain sequence motives may furnish
clues to ethnic groups. The report presents three cases illustrating the
application possibilities of mtDNA typing in forensic practice.
PMID- 11006827
TI - Dietary carbohydrates affect caecal fermentation and modify nitrogen excretion
patterns in rats. I. Studies with protein-free diets.
AB - In a two-factorial experiment on 96 young male rats, the effects of substituting
10% raw potato starch (PS), pectins (PEC), or cellulose (CEL) for corn starch
(CS) were studied using an unsupplemented protein-free (PF) diet or a PF diet
supplemented either with DL-methionine or urea. The pH and the short chain fatty
acids (SCFA) content in caecal digesta, as well as caecal digesta and tissue
weights were determined and used as the criteria of caecal fermentation
intensity. Blood urea level, amount of N excreted via faeces and urine, DAPA
content, and amino acid composition of faecal protein were analyzed as indices of
protein metabolism. A 10-day adaptation period to the carbohydrates fed with the
casein diet preceded the experimental period of feeding the respective
carbohydrates with protein-free diets. Dietary carbohydrates significantly
influenced total and individual SCFA content in caecal digesta, as well as other
parameters related to the intensity of fermentation. Potato starch and pectins
were more intensively fermented than cellulose. Supplementation of the PF diet
with methionine and urea affected only caecal isobutyric and valeric acid content
in a way dependent on the carbohydrates present in the diet. Carbohydrates
significantly altered the routes of N excretion. Faecal excretion was increased
by all carbohydrates studied compared to corn starch, pectins had the most marked
effect. Urinary excretion was significantly increased by cellulose (as compared
with the PEC and PS groups) and decreased by pectins as compared with all other
groups. There was an interaction between the effects of carbohydrates and type of
protein-free diet on faecal and urinary excretion. The sum of amino acids in
faecal protein was the lowest on the PEC diet, but the amino acid composition
expressed as a per cent of total amino acid content was similar in all groups. It
can be concluded that dietary carbohydrates alter the excretion patterns of
endogenous nitrogen in rats in different ways and that this effect is related to
the intensity of their fermentation in the hind gut.
PMID- 11006828
TI - Effects of vitamin B6 supplementation in rats during lactation on vitamin B6
concentration and transaminase activities in the offspring.
AB - The aim of the present investigation was to study the effect of a varying
maternal vitamin B6 supplementation during lactation period on vitamin B6 levels
in blood, liver and total body, and on the activity of two transaminase enzymes
in the offspring. Therefore, eighty female Sprague-Dawley rats were fed a semi
synthetic diet (0.2 mg vitamin B6 per kg) which was supplemented during gravidity
with 5 mg vitamin B6 per kg diet. During the following lactation period the rats
were assigned to one of 10 vitamin B6 treatment groups (supplementation of 0, 3,
6, 9, 12, 15, 18, 36, 360, 3600 mg vitamin B6 per kg diet). At day 14 of
lactation the pubs of all dams were decapitated and blood, liver, and carcass
were used for analysis of vitamin B6 concentration, activities of two
transaminases, aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) in plasma, erythrocytes, and liver, and of haematological parameters. While
the liver and total body wet weights as well as the haematological parameters
(red blood cells, haemoglobin concentration, hematocrit, middle corpuscular cell
volume, middle corpuscular haemoglobin, middle corpuscular haemoglobin
concentration) did not differ within the experimental groups, the present data
clearly show that in blood, liver and total body of the offspring exists a slight
dose-response relationship between the maternal dietary vitamin B6
supplementation and the vitamin B6 concentration. Concerning the activities of
the transaminases a dietary supplementation above 3 mg vitamin B6 per kg diet had
no influence on the AST and ALT activities in offspring plasma. In the
erythrocytes no statistical significant influence of the vitamin B6
supplementation during lactation on the activities of AST and ALT was found. The
activities of ALT and AST in liver were not consistently altered by the vitamin
B6 supplementation of the dams during lactation. In conclusion these results
indicate that a minimal maternal dietary vitamin B6 supply of 3.1 mg per kg diet
is necessary with regard to health and development of their offspring. But not
all of the analysed parameters as the liver and total body weights, the
activities of AST and ALT in the erythrocytes, and the haematological parameters
were influenced by a deficient maternal dietary vitamin B6 supply.
PMID- 11006829
TI - Fermentation of carbohydrates and yield of microbial protein in mixed cultures of
rabbit caecal microorganisms.
AB - Fermentation pattern and yields of microbial protein were investigated in
cultures of the rabbit caecal contents supplied with glucose, xylose, starch,
pectin and xylan. Rabbits at the age of 4 weeks (before weaning) and 3 months
were slaughtered, their caecal contents added at 1.1% to growth media and
incubated anaerobically at 39 degrees C for 18 h. Caecal microorganisms of 4-week
old rabbits produced no methane and caproate, less butyrate, but more propionate
than microorganisms of 3-month-old rabbits. In both groups of rabbits,
fermentation of xylose produced significantly more propionate and less butyrate
than fermentation of glucose. More propionate and less acetate was formed from
starch than from pectin. In caecal cultures from 4-week-old rabbits with pectin,
the molar percentages of acetate was significantly higher and percentages of
other short-chain fatty acids (SCFA) lower than in cultures with starch or xylan.
In cultures from 3-month-old rabbits, fermentation of pectin and xylan produced
similar SCFA profiles, different from SCFA molar composition in cultures with
starch. Average production of microbial protein was 129 mg per 1 g of
carbohydrate digested (range 110 to 141 mg/g). Protein yields were the same on
glucose and xylose, but nonsignificantly higher on starch than on pectin and
xylan. It can be concluded that the characteristics of substrate affected
fermentation pattern in mixed cultures of rabbit caecal microorganisms. Substrate
effects on protein yields were not statistically significant, due to high
variation.
PMID- 11006830
TI - Estimation of net nutrient oxidation and lipogenesis in growing pigs.
AB - Data from previous series of trials were reevaluated in order to quantify the net
nutrient oxidation and lipogenesis by combining data from balance experiments and
indirect calorimetry measurements. The experiments were carried out with eight
castrated males of Danish Landrace measured individually from 30 to 100 kg BW.
All pigs were fed alternately on high feeding level, near ad libitum and on low
feeding level, near maintenance. Oxidation of carbohydrate (OXCHO) and fat (OXF)
was calculated from gas exchange measurements. On high feeding level the
contribution from OXCHO and OXF to the total heat production was 55 and 30%,
respectively, at 30 kg BW and fairly constant from 60 kg BW with OXCHO around 80%
and no net OXF. At low feeding level the contribution from OXCHO and OXF was 28
and 63%, respectively, at 30 kg BW, increasing to 52% for OXCHO and decreasing to
37% for OXF at 95 kg BW. The lipogenesis on high feeding level increased from 2.4
to 11.9 MJ/d, while on low feeding level it increased from 2.5 to 3.6 MJ/d at 30
to 95 kg BW. The intake of carbohydrate was too low to cover energy requirement
by OXCHO on low feeding level and in the first periods on high feeding level and
OXF occurred. In spite of a deficit of carbohydrate for oxidation a part of
carbohydrate (2.6 MJ/d, approximately 150 g/d) was used for fat synthesis,
indicating an importance of lipogenesis in growing pigs.
PMID- 11006831
TI - The influence of potato fibre on exocrine pancreatic secretions and on plasma
levels of insulin, secretin and cholecystokinin in growing pigs.
AB - The effect of a potato fibre preparation on exocrine pancreatic secretions and on
gastrointestinal hormone levels in plasma was studied in three 8 weeks old
piglets that were surgically fitted with a jugular vein catheter for blood
sampling, a pancreatic duct catheter and a T-shaped duodenal cannula for
collection of pancreatic juice. The animals were fed for 2 weeks a control diet
(experimental period 1), thereafter for 2 weeks the control diet supplemented
with 2% potato fibre (experimental period 2) and for another 2 weeks the control
diet again (experimental period 3). Additionally, intraduodenal (i.d.) infusions
of the experimental diet, the control diet and potato fibre as well as i.v.
infusions of a solution containing cholecystokinin (CCK) and secretin were
administered. Potato fibre in the diet evoked in tendency an increase in the
volume of secretion of pancreatic juice and a significant increase both in the
mean values of the total protein content and total activities of lipase, trypsin
and alpha-amylase when compared to the control diet. The i.d. infusion of the
control diet, experimental diet and fibre infusate as well as the i.v.
administration of the hormone infusate led to a spontaneous secretory response of
the exocrine pancreas. Besides gastrointestinal hormones, such as CCK, other
factors such as short chain fatty acids may be involved in the regulation of the
exocrine pancreas.
PMID- 11006832
TI - Development of an in vitro incubation technique for the estimation of the
utilizable crude protein (uCP) in feeds for cattle.
AB - An in vitro incubation technique based on the first stage of the in vitro
digestion technique published by Tilley and Terry (1963) was developed to
estimate the utilizable crude protein (uCP) of single feeds and feed mixtures as
non ammonia-N after 24 h of incubation. The results of 25 feed samples showed
that there was a significant relationship between the uCP values calculated by
regression based on in vivo data sets (Y, CP [g.kg-1 DM]) and those measured by
the in vitro incubation technique (X, CP [g.kg-1 DM], 24 h incubation): y = 0.85x
+ 18.0, r2 = 0.84, P < or = 0.001. It was concluded that it can be possible to
determine the uCP value of single feeds or feed mixtures by this in vitro
incubation technique and to estimate the uCP value of feeds by this regression
equation.
PMID- 11006833
TI - Investigations on the influence of duodenal histidine infusion on nitrogen and
amino acid turnover of growing German Holstein bulls.
AB - The effect of a continuous duodenal infusion of L-histidine (His) (8 g/d) on the
retention of nitrogen was investigated in two experiments (I, II), each of which
was carried out using two young bulls. In Exps. I and II, the animals (150-250 kg
BW) were fitted with a re-entrant cannula in the proximal duodenum and were fed
diets containing 125 g CP/kg DM and 11.5 MJ ME/kg DM. A third experiment (III)
using two young bulls (140-200 kg BW) fitted with a simple T-cannula was carried
out infusing 6 g L-His. The animals were fed a low protein diet (94 g CP/kg DM
and 11 MJ ME/kg DM). The study was done to find out whether or not L-His is the
first limiting amino acid (AA) for growing ruminants. N retention was 28 and 31,
38 and 38, 22 and 24 g/d without L-His infusion and with L-His infusion for Exps.
I, II and III, respectively. Both in the experiments with a standard protein
supply (I, II) and in the experiment with reduced protein supply (III), no
significant differences were found between periods with and without infusion of L
His. The utilisation of duodenal NAN varied between 39% and 50% and was also not
significantly influenced by the duodenal infusion of L-His. No significant effect
was observed on the flow of AA into the duodenum. The faecal excretion of AA was
also not significantly influenced by the infusion of L-His. The utilisation of
individual amino acids as calculated by the ratio of retained AA to intestinal
apparently digested AA, did not differ significantly following the duodenal
infusion of L-His. As expected, the utilisation of His decreased. Of the
different essential AA, L-His was the most utilised (80%) followed by Arg (72%),
Met (60%), Leu (45%) and Lys (44%), during periods without supplementation of L
His. It is concluded that the intestinal supply of L-His from the basal diet was
sufficient for the potential growth level of animals under these experimental
conditions. In all AA present at the proximal duodenum, L-His could have at first
a limiting effect on the performance of growing young bulls with high body gain.
Arg and Met, but not Lys, could be second or co-limiting AA.
PMID- 11006834
TI - Use of health economics for decision-making in complex emergencies. Report of a
WHO-FICOSSER meeting. Paris, 16-18 December, 1999.
PMID- 11006835
TI - [Comparison of databases of the medical profession: an example in anatomy and
pathological cytology].
AB - Medical demographic regulation policy is supported by statistical descriptive and
prospective studies on the actual and future supply of medical practitioners. Two
main data bases are available in France for these analyses one at the Ministry of
Health and the other at the French Medical Council. While both are supposed to be
exhaustive and reliable, the official publications of the two institutions
provide different data. It is difficult to assess the actual number of French
doctors. The task is even more problematic for each individual medical or
surgical specialty. Using the medical specialty Pathology as an example, this
article compares the quality of the different data bases and underlines some of
the structural and dynamic problems which could interfere with the validity of
the information. Better cooperation between the different institutions involved
would be helpful to contribute to the quality of the data bases and the
organization of the medical specialty.
PMID- 11006836
TI - [Malaria at the dawn of the millennium: lessons taken from the literature].
AB - The entomological approach has dominated in the past the geographical-
epidemiological study of malaria. Nowadays, new approaches are considering
aspects such as representations, attitudes to adopt, change in the transmission
process according to the ecosystems. The geographical approach here highlighted
implies firstly the knowledge of the geo-epidemiology at the small areas love.
This approach should also consider the entomological parameters, the
environmental factors and the therapeutic behaviors in order to evaluate the
efficiency of the action programmes.
PMID- 11006837
TI - Phenotypic and genetic characterization of Paecilomyces lilacinus strains with
biocontrol activity against root-knot nematodes.
AB - Efficient selection of fungi for biological control of nematodes requires a
series of screening assays. Assessment of genetic diversity in the candidate
species maximizes the variety of the isolates tested and permits the assignment
of a particular genotype with high nematophagous potential using a rapid novel
assay. Molecular analyses also facilitate separation between isolates, allowing
the identification of proprietary strains and trace biocontrol strains in the
environment. The resistance of propagules to UV radiation is an important factor
in the survival of a biocontrol agent. We have analyzed 15 strains of the
nematophagous fungus Paecilomyces lilacinus using these principles. Arbitrarily
primed DNA and allozyme assays were applied to place the isolates into genetic
clusters, and demonstrated that some genetically related P. lilacinus strains
exhibit widespread geographic distributions. When exposed to UV radiation, some
weakly nematophagous strains were generally more susceptible than effective
isolates. A microtitre tray-based assay used to screen the pathogenic activity of
each isolate to Meloidogyne javanica egg masses revealed that the nematophagous
ability varied between 37%-100%. However, there was no clear relationship between
nematophagous ability and genetic clusters. Molecular characterizations revealed
sufficient diversity to allow tracking of strains released into the environment.
PMID- 11006838
TI - Stoichiometry of diauxic growth of a xylanase-producing Bacillus strain.
AB - In this work, the establishment of material balances and stoichiometry of the
growth of Bacillus sp. was undertaken. This strain produces high quantities of a
xylanase suitable for use as bleach boost agent in chlorine-free bleaching
sequences of paper pulp. As carbon dioxide plays an important role as a growth
factor, bacterial growth in two fermentations, one fed with air and another fed
with carbon-dioxide-enriched air, were compared. For this purpose, a method
permitting the determination of the consumption of the two carbon sources, xylan
and peptone, was proposed. The material balances revealed that in both cases, the
bacteria first use peptone as their carbon source, and then xylan in the second
part of the growth phase. The aerated culture showed diauxic growth on these two
substrates, whereas carbon-dioxide-enriched air caused disappearance of the
metabolic adaptation phase, and rendered biomass production more economic. The
fermentation fed with air needed 30% more xylan than the fermentation fed with
carbon-dioxide-enriched air for the same quantity of biomass produced.
PMID- 11006839
TI - Effects of experimental conditions on mycorrhizal relationships between Pinus
sylvestris and Lactarius deliciosus and unprecedented fruit-body formation of the
Saffron milk cap under controlled soilless conditions.
AB - The mycorrhizal relationships between pines and two edible species of Lactarius
sect. Dapetes were investigated by optimizing the experimental conditions of
mycelial growth and of mycorrhizal colonization of pine seedlings. In vitro
mycelial growth of Lactarius deliciosus and L. sanguifluus was improved on a
buffered medium containing glucose, amino acids, and vitamins. Two methods of
mycorrhization of pines with Lactarius deliciosus were tested. The mycorrhizal
colonization was rapid and intense under non-aseptic conditions with a low
nutrient supply and without exogenous glucose. A positive influence of
mycorrhizal colonization on Pinus sylvestris growth was subsequently observed.
Under axenic conditions and with a high nutrient supply, mycorrhization was
stimulated at 10 g/L of exogenous glucose, irrespective of the phosphorus
concentration. At high phosphorus level (1 mM) and 0.1, 1.0, or 10.0 g/L glucose,
growth of Pinus sylvestris was reduced by inoculation. Stability and development
of Pinus spp./Lactarius deliciosus symbioses were assayed in a climatic chamber
using containers filled with a synthetic substrate. Over a 2-year culture period,
the root systems of the pine seedlings were heavily colonized by Lactarius
deliciosus. One year following inoculation, Lactarius deliciosus fruit-body
primordia appeared associated with Pinus sylvestris seedlings. Six months later,
two mature basidiomata were obtained. This is the first report of soilless fruit
body formation of this edible mushroom.
PMID- 11006840
TI - Localization of fungal fimbriae by immunocytochemistry in pathogenic and
nonpathogenic isolates of Venturia inaequalis.
AB - Pathogenic and nonpathogenic isolates of Venturia inaequalis were grown in liquid
culture. Hyphae were treated with two types of fimbrial antiserum (AU- and AV-1)
and examined by immunofluorescent microscopy, in order to establish the
distribution of fimbrial epitopes in whole cell mounts. The AV-1 antiserum was
specific for the glycoprotein subunits while the AU-antiserum was specific for
the protein moieties present on the fimbriae of Mycobotryum violaceum. The use of
fimbrial antiserum with immunocytochemistry and transmission electron microscopy
demonstrated a clear distinction between pathogenic and nonpathogenic isolates of
V. inaequalis, based on the appearance of the fungal cell wall and the
distribution of fimbrial epitopes labeled with AV-1 antiserum and immunogold
complex. In actively growing hyphae of the pathogenic isolate, characterized by
distinct cellular organelles, small vacuoles, and lipid bodies, fimbrial epitopes
were concentrated in the fungal cell wall and were present minimally on the outer
surface. In contrast, actively growing hyphae of the nonpathogenic isolate of V.
inaequalis had extensive fine hair-like protrusions in the fungal cell wall which
labeled with the AV-1 antiserum and immunogold. The distribution of fimbrial
epitopes in V. inaequalis was highly dependent on the developmental growth stage
of the fungal mycelium. Aging mycelia in both the pathogenic and nonpathogenic
isolates of V. inaequalis were characterized by a large central vacuole and no
label. In the pathogenic and nonpathogenic isolates of V. inaequalis grown in
vitro, the distribution of fimbrial glycoprotein epitopes provided a more complex
profile than that seen in M. violaceum.
PMID- 11006842
TI - Physical degradation of wheat straw by the in-vessel and windrow methods of
mushroom compost production.
AB - Mushroom compost manufacturers in Ireland are moving away from the traditional
outdoor phase I windrow method, favouring in-vessel production. Composters and
growers have reported better quality compost with faster spawn run and higher
yields produced by this process. In the present study, physical examination of
samples highlighted differences when comparing the windrow and in-vessel methods
of compost production. Observations using scanning electron microscopy suggest
that the cuticle of wheat straw from in-vessel production is damaged during phase
I, peeling away from the surface in fragments, and exposing the epidermis.
Changes in silicon levels on the straw surface acted as a marker for cuticle
damage when comparing both composting systems. Cuticle damage may be important
during composting and afterwards, as substrate colonisation is faster, and
consequently spawn run is shorter. The phase I compost microbial community is
altered by the in-vessel technique, producing a predominantly thermophilic
bacterial flora in contrast to the mesophilic and thermophilic bacteria and fungi
found in windrow phase I compost. These differences may be significant in
mushroom compost production.
PMID- 11006841
TI - Development of formulations of biological agents for management of root rot of
lettuce and cucumber.
AB - The effect of various carrier formulations of Bacillus subtilis and Pseudomonas
putida were tested on germination, growth, and yield of lettuce and cucumber
crops in the presence of Pythium aphanidermatum and Fusarium oxysporum f.sp.
cucurbitacearum, respectively. Survival of B. subtilis and P. putida in various
carriers under refrigeration (about 0 degree C) and at room temperature (about 22
degrees C) was also studied. In all carrier formulations, B. subtilis strain BACT
0 survived up to 45 days. After 45 days of storage at room temperature (about 22
degrees C), populations B. subtilis strain BACT-0 were significantly higher in
vermiculite, kaolin, and bacterial broth carriers compared with other carriers.
Populations of P. putida were significantly higher in vermiculite, peat moss,
wheat bran, and bacterial broth than in other carriers when stored either under
refrigeration (about 0 degree C) or at room temperature (about 22 degrees C) for
15 or 45 days. Germination of lettuce seed was not affected in vermiculite, talc,
kaolin, and peat moss carriers, but germination was significantly reduced in
alginate and bacterial broth carriers of B. subtilis compared to the non-treated
control. Germination of cucumber seed was not affected by any of the carriers.
Significantly higher fresh lettuce and root weights were observed in vermiculite
and kaolin carriers of B. subtilis compared with P. aphanidermatum-inoculated
control plants. Lettuce treated with vermiculite, and kaolin carriers of B.
subtilis, or non-inoculated control lettuce plants had significantly lower root
rot ratings than talc, peat moss, bacterial broth, and P. aphanidermatum
inoculated control plants. Growth and yield of cucumber plants were significantly
higher in vermiculite-based carrier of P. putida than the other carriers and
Fusarium oxysporum f.sp. cucurbitacearum-inoculated plants.
PMID- 11006843
TI - Cholesterol is accumulated by mycobacteria but its degradation is limited to non
pathogenic fast-growing mycobacteria.
AB - In this report we show that fast-growing non-pathogenic mycobacteria degrade
cholesterol from liquid media, and are able to grow on cholesterol as a sole
carbon source. In contrast, slow-growing mycobacteria, including pathogenic
Mycobacterium tuberculosis and bacillus Calmette-Guerin (BCG), do not degrade and
use cholesterol as a carbon source. Nevertheless, pathogenic mycobacteria are
able to uptake, modify, and accumulate cholesterol from liquid growth media, and
form a zone of clearance around a colony when plated on solid media containing
cholesterol. These data suggest that cholesterol may have a role in mycobacterial
infection other than its use as carbon source.
PMID- 11006844
TI - A physical and genetic map of the Mycoplasma hyopneumoniae strain J genome.
AB - A macrorestriction map of the genome of Mycoplasma hyopneumoniae strain J, the
type strain of the causative agent of enzootic pneumonia in pigs, was constructed
using pulsed-field gel electrophoresis (PFGE) and DNA hybridization. The size of
the genome as determined by PFGE was approximately 1070 kb. Assembly of the M.
hyopneumoniae genomic map was facilitated and complimented by the simultaneous
construction of an ordered cosmid library. Five contigs of overlapping cosmids
were assembled, which together represent coverage of approximately 728 kb. Forty
two genetic markers (including three types of repeated elements) were placed on
the M. hyopneumoniae map. Closer examination of an ApaI restriction fragment
contained entirely within a single cosmid insert suggests that the genome size
may be overestimated by PFGE.
PMID- 11006845
TI - High-frequency interconversion of turbid and clear plaque strains of
bacteriophage f1 and associated host cell death.
AB - Under normal cultivation conditions, a mixture of turbid and clear plaques is
often apparent in cultures of bacterial cells infected with filamentous
bacteriophages. Beginning with a culture of wild-type filamentous phage f1, which
itself produces turbid plaques, a clear plaque strain (c1) was isolated. From c1,
the turbid plaque strain t1 was isolated; from t1, the clear plaque strain c2 was
isolated; and from c2, the turbid plaque strain t2 was isolated. Each of these
strains was generated with a frequency of approximately 1 x 10(-4). Although
filamentous phages have been thought not to induce host cell death, both turbid
and clear plaque strains of f1 killed host bacteria. Plating of bacterial cells 1
h after infection revealed that colonies produced by cells infected with either
wild-type f1 or strain c2 were smaller than those derived from uninfected cells,
and that colony formation by infected cells was reduced by 15% and 38%,
respectively. The time course of bacterial growth revealed that, at 4 h after
infection, the number of CFU per milliliter of culture of cells infected with
wild-type f1 or with strain c2 was reduced by 27% and 95%, respectively, compared
with that for uninfected cells. Microculture analysis also revealed that the
percentages of nondividing cells in f1 or c2 infected were 19% and 52%,
respectively, 4 h after infection with wild-type f1 or with strain c2; no such
cells were detected in cultures of uninfected cells. Negative staining and
electron microscopy showed that 20% and 61% of cells infected with wild-type f1
or with strain c2 were dead 4 h postinfection. Finally, although the rates of DNA
synthesis were similar for infected and uninfected cells, the rates of RNA and
protein synthesis were markedly reduced in infected cells.
PMID- 11006846
TI - Cloning of the histidine biosynthetic genes from Corynebacterium glutamicum:
organization and analysis of the hisG and hisE genes.
AB - The physically linked hisG and hisE genes, encoding for ATP
phosphoribosyltransferase and phosphoribosyl-ATP-pyrophosphohydrolase were
isolated from the Corynebacterium glutamicum gene library by complementation of
Escherichia coli histidine auxotrophs. They are two of the nine genes that
participate in the histidine biosynthetic pathway. Molecular genetics and
sequencing analysis of the cloned 9-kb insert DNA showed that it carries the hisG
and hisE genes. In combining this result with our previous report, we propose
that all histidine biosynthetic genes are separated on the genome by three
unlinked loci. The coding regions of the hisG and hisE genes are 279 and 87 amino
acids in length with a predicted size of about 30 and 10 kDa, respectively.
Computer analysis revealed that the amino acid sequences of the hisG and hisE
gene products were similar to those of other bacteria.
PMID- 11006847
TI - Purification and characterization of a 4-hydroxybenzoate decarboxylase from an
anaerobic coculture.
AB - The oxygen-sensitive 4-hydroxybenzoate decarboxylase (4OHB-DC) activity from a
phenol-carboxylating coculture, consisting of Clostridium-like strain 6 and an
unidentified strain 7, was studied. Assays done with cell extracts showed that
the optimal pH was 5.0-6.5 and the Km was 5.4 mM. The activity decreased by 50%
in the presence of 5 mM EDTA, and it was restored and even enhanced by the
addition of Mg++, Mn++, Zn++, or Ca++. After purification, the molecular mass of
the enzyme was estimated as 420 kDa by gel chromatography, and as 119 kDa by SDS
PAGE, suggesting a homotetrameric structure. Its pI was 5.6. The N-terminal amino
acid sequence showed 95% and 76% homology with the pyruvate-flavodoxin
oxidoreductase (nifJ gene product) from Enterobacter agglomerans and Klebsiella
pneumoniae, respectively. The purified enzyme also slowly catalyzed the reverse
reaction, that is the phenol carboxylation. These characteristics suggest that
this enzyme is different from other known decarboxylases. This includes the 4OHB
DC from Clostridium hydroxybenzoicum, which is the only one that had been
purified before.
PMID- 11006848
TI - Production of cellulases and xylanases by low-temperature basidiomycetes.
AB - Three of four isolates, representing phylogenetically distinct groupings of low
temperature basidiomycetes (LTB), were capable of utilizing wheat straw, and to a
lesser extent conifer wood at 15 degrees C. A cottony snow mould LTB (LRS 013)
and a fruit rot LTB (LRS 241) grown on straw significantly degraded filter paper,
carboxymethylcellulose (CMC), p-nitrophenyl beta-glucopyranoside (i.e., beta
glucosidases), and xylan. Enzymes produced by Coprinus psychromorbidus (LRS 067)
were limited to xylanases from straw and wood and beta-glucosidases from wood. A
sclerotia-forming LTB (LRS 131) exhibited poor growth on both substrates, and did
not produce detectable quantities of extracellular enzymes. None of the LTB
isolates tested degraded avicel. The temperature optima of CMCases and xylanases
in the filtrates from the straw medium ranged from 25 degrees C to 55 degrees C,
and with the exception of LRS 067, significant activity was observed at 5 degrees
C. Two cellulases (25 and 31 kDa) and two xylanases (24 and 34 kDa) were observed
on zymograms for LRS 013 and 241. Reduction of enzymes with 2-mercaptoethanol
adversely affected their activity on zymograms, and an additional cellulase band
was observed for non-reduced samples. This study indicates that LTB produce an
array of cellulolytic and xylanolytic enzymes, and that some of these enzymes
possess low-temperature optima which may facilitate degradation of plant fibre
under low-temperature conditions.
PMID- 11006849
TI - Photo quiz: urticaria pigmentosa.
PMID- 11006850
TI - What's eating you? Pulex irritans.
PMID- 11006851
TI - Multiple fire ant stings: report of 3 cases and review of the literature.
AB - Imported fire ant sting reactions are becoming an increasing problem in the
United States. It is important for clinicians to be familiar with their possible
cutaneous and noncutaneous presentations. We present 3 cases with multiple fire
ant stings, followed by a review of the literature.
PMID- 11006852
TI - Subacute cutaneous lupus erythematosus: report of a patient who subsequently
developed a meningioma and whose skin lesions were treated with isotretinoin.
AB - Cancer has been reported in patients with systemic lupus erythematosus (SLE). A
possible association of the development of hematologic malignancies in patients
with SLE has been suggested. In some patients, subacute cutaneous lupus
erythematosus, a distinct subset of lupus erythematosus, has appeared, resolved,
or both as a solid tumor-related paraneoplastic syndrome. A woman in whom a
meningioma was diagnosed 44 years following the onset of subacute cutaneous lupus
erythematosus is described; her skin lesions improved after starting isotretinoin
therapy. The relationship between lupus erythematosus and neoplasia is summarized
and the management of subacute cutaneous lupus erythematosus with retinoids is
reviewed.
PMID- 11006853
TI - Spiny keratoderma.
AB - Spiny keratoderma is a descriptive term used to encompass a variety of unusual,
disparate keratodermas. Spiny keratoderma has been associated with lipid
abnormalities and has been limited to the palms and soles in some individuals. We
describe an acquired case of spiny keratoderma in which an adult woman developed
filiform lesions predominating on the trunk and proximal extremities. Treatment
with topical emollients and keratolytic agents was unsuccessful, but topical
tazarotene led to long periods of resolution. She has had no other associated
abnormalities. The clinical features and differential diagnosis of spiny
keratoderma are reviewed.
PMID- 11006854
TI - Rapidly progressive fatal cutaneous T cell lymphoma with a trauma-related
presentation.
AB - A case of rapidly progressive cutaneous T cell lymphoma with a trauma-related
presentation in a 73-year-old man is reported. Clinically, the patient presented
with an ulcerated cutaneous mass at the site of trauma-related hematoma of the
leg. The histopathology was that of tumor phase cutaneous T cell lymphoma with
involvement of the skin and subcutis. The diagnostic challenge of this clinical
presentation and the rapidly progressive course are highlighted.
PMID- 11006855
TI - Kimura's disease presenting as subcutaneous facial plaque in an African American.
AB - Kimura's disease is a benign, uncommon, chronic inflammatory condition that
usually presents with painless subcutaneous nodules or plaques in the head and
neck region. Although the disease is predominantly found in Asian populations,
there are occasional cases reported among Caucasians and rare occurrences in
African populations. The etiology and pathogenesis of the disease are unknown and
the clinical presentation can mimic several benign and malignant disease states.
The accurate diagnosis of Kimura's disease is based on clinical and
histopathological findings. There is no evidence of malignant transformation and
occasional spontaneous resolution occurs. Various treatment modalities have been
suggested in the management of this condition. Oral corticosteroids have been the
mainstay of therapy, even though steroid withdrawal can result in lesion
recurrence.
PMID- 11006856
TI - Disseminated cryptococcosis presenting as pseudofolliculitis in an AIDS patient.
AB - We report the case of a 42-year-old man with AIDS and an unusual presentation of
disseminated cutaneous cryptococcosis. The eruption was characterized by
excoriated papules of the upper body and was initially diagnosed as folliculitis.
A pseudofollicular eruption is a rare presentation for disseminated
cryptococcosis.
PMID- 11006857
TI - Multiple onychocryptosis following treatment of onychomycosis with oral
terbinafine.
AB - The authors report an unusual case of multiple onychocryptosis, which developed
following treatment of onychomycosis with oral terbinafine. With new growth of
the healthy nail plate, the distal aspect of multiple toenails became ingrown
with periungual inflammation. This required several minor surgical procedures to
alleviate the onychocryptosis. The authors present this case report as a
potential complication of oral antifungal therapy.
PMID- 11006858
TI - Superficial granulomatous pyoderma.
AB - We report the case of a 30-year-old man who, from the age of 16, presented with
abscess-type lesions that turned into ulcers with a torpid course and with
histopathologic characteristics of superficial granulomatous pyoderma. The
patient has been followed for 6 years, during which time the only treatment
necessary to prevent recurrence of lesions has been the administration of
different doses of minocycline.
PMID- 11006859
TI - Herpes zoster in the medically healthy child and covert severe child abuse.
AB - Herpes zoster is associated with depressed cell-mediated immunity and occurs
rarely in the medically healthy nonimmunocompromised child. We report 4 cases of
childhood-onset herpes zoster in the absence of a medical disorder. All 4
patients reported experiencing severe, chronic child abuse when the herpes zoster
first appeared. It is possible that the severe chronic psychologic stress
resulting from the abuse depressed the patients' cell-mediated immune status and
thereby predisposed them to herpes zoster. Our findings suggest that the
clinician's suspicion should be heightened for the possibility of covert child
abuse and secondary stress when managing an otherwise apparently healthy child
with herpes zoster.
PMID- 11006860
TI - [Johann Nepomuk Czermak as a neurophysiologist in Leipzig].
AB - Johann Nepomuk Czermak (1828-1873) gained a lasting reputation in the fields of
laryngology, rhinology and dentistry. However, his works in the discipline he
liked most--neurophysiology--have almost been forgotten. This paper focuses on
those articles, which Czermak wrote during his last years in Leipzig (from 1869).
Also it was here that he was finally able to fulfill his dream of a
"spectatorium", a perfect place for both research and teaching at that time. This
institution was the perfect expression of Czermak's uncompromisingly scientific
approach, his views in social as well as matters of teaching. It is part of his
tragedy though, that Czermak died too early in Leipzig, the place where he could
finally realize many of his scientific visions, and that his inheritance was soon
forgotten.
PMID- 11006861
TI - [Positron emission tomography in diagnosis and prognosis of postanoxic cerebral
dysfunctions].
AB - Clinical signs, laboratory tests, EEG or evoked potentials only permit an
indirect estimation of the extent of structural brain damage following severe
global brain anoxia. Positron emission tomography (PET) permits additional
insights into the extent of neuronal damage in acute and persistent postanoxic
vegetative states (VS). PET documents a severe and irreversible damage of
supratentorial cortical structures in postanoxic VS and allows its differential
diagnosis from related disorders, e.g. the locked-in-syndrome. PET clearly
distinguishes functional alterations in VS from those in non-REM sleep and
documents that patients in VS are not in a sleep-like condition, but in a state
closely related to deep anesthesia. Furthermore, the extent of impairment of the
residual cortical glucose consumption yields information concerning the possible
recovery of consciousness and neuronal function in VS. In combination with
clinical, laboratory and neurophysiological findings, PET may be helpful to
establish the individual prognosis in acute VS.
PMID- 11006862
TI - [The EEG as an indicator of cholinergic deficit in Alzheimer's disease].
AB - There are tight relationships between the EEG and the activity of the cholinergic
system. The excitability of cortical neurons is increased by the ascending
cholinergic projections of the nucleus basalis of Meynert. Cholinergic
deafferentiation of the cortex leads to an increase of slow-wave EEG activity.
Cholinergic deficit is a typical feature of Alzheimer's disease. It is goes along
with characteristic EEG alterations, mainly increased activity in the slow
frequency bands. The amount of EEG alterations increases as the disease
progresses. It is correlated with the severity of symptoms, neuropsychological
performance, cerebral perfusion, cerebral glucose utilization and the extent of
histopathological changes. EEG alterations are a valuable diagnostic tool in
Alzheimer's disease. They may be suited for early diagnosis and may allow the
prediction of the therapeutic response to cholinergic drugs.
PMID- 11006863
TI - [The effect of the menstruation cycle on manifestations of pychiatric diseases].
AB - In the present study we investigated whether a correlation exists between
menstrual cycle phase on the day of an acute psychiatric admission and diagnostic
entities. Therefore we assessed the menstrual cycle phase in 155 women at the
time of acute admission for any non-organic psychiatric disorder. A specific
diagnosis according to ICD-10-criteria and to Leonhard's nosology was established
without knowledge of the menstrual cycle phase. Independent of diagnosis and
classification, the majority of patients (57%) was admitted during the pre
menstrual/menstrual period. Comparing the frequencies of admission before
(increasing blood-estrogen-level) and after ovulation (decreasing blood-estrogen
level) we found using ICD-10 criteria there were no significant differences
between affective psychoses (F3), acute polymorphous psychotic disorder (F23),
schizophrenia/schizoaffective psychoses (F20 and F25) and patients suffering from
neuroses or personality disorders (F4-F6). Applying Leonhard's criteria we found
no significant differences between endogeneous psychoses and personality
disorders and no significant differences between cycloid psychoses and affective
psychoses or affective psychoses and schizophrenias as well. However, patients
with cycloid psychoses were significantly more frequently admitted to hospital
during the luteal-/menstrual phase than patients with schizophrenia (chi 2-Test,
p = 0.02). These findings do not confirm a specificity of a pre-menstrual
exacerbation of psychotic symptoms for schizophrenia. Rather we found cycloid
psychoses to be significantly more frequently associated with premenstrual
exacerbation of symptoms.
PMID- 11006864
TI - [Normative needs for care of schizophrenics: a useful concept for community
psychiatric planning?].
AB - One step in a public health research project focuses on the analysis of the
individual (expert-based) normative needs for mental health care of chronic
schizophrenic patients (n = 115) in the Dresden Region during the first year post
hospital release and the extent to which this can be met by the current
established level of complementary care. It is an exemplary contribution to the
evaluation of community psychiatry as restructured in the Free State of Saxony
following German reunification. The results of the study can be condensed to the
following interpreting essential statements. Schizophrenics' normative needs for
care are not a statistical issue. The single case analysis corroborates a high
rate of relevant fluctuations, above all within the clinical sector (e.g.
concerning "dyskinesias and other side effects"), that pose a particular
challenge to the flexibility of a system of community psychiatry. This includes
that the consequence for the practice of care implies then that when diagnosing
course, attention must be paid to shifts in the content of the needs for mental
health care (e.g. increasing importance of factors, which contain impairments of
basic social competences) in order to orient to them any health care measures
already initiated.--With the aid of the used research instrument (Needs for Care
Assessment) deficits in meeting the needs for care can be identified. In the
Dresden Region considerable deficits persist apparently in the subsections
recreational activities and occupational and communication skills, which can be
ascribed to the lack of appropriate institutions of care in the area.--The
normative needs for care of schizophrenic patients cannot be determined simply on
the basis of a few, quickly identifiable markers. Rather it demands
individualized analysis incorporating variables pertaining to psychopathology,
subjective coping, social competence and the course of the disorder. The
development of the needs for care over the period of one year can apparently be
predicted by trends in the social sector that are already visible within the
first months. With regard to aspects of care planning this finding illustrates
the limited ability of cross-section surveys to make definitive statements, as
well as the predominance of social disabilities over the entire spectrum of the
normative needs for psychiatric care.
PMID- 11006866
TI - [Communications of the Viktor von Weizscker Society e.V].
PMID- 11006865
TI - [Political change in East Germany 1989-90 in the lives of chronic schizophrenic
patients].
AB - Theoretical models suggest a higher vulnerability of chronic schizophrenic
patients for critical life events and rapid change of objective living
circumstances. On the basis of these models one may hypothesise that the
political change in East Germany in 1989/90 was objectively or subjectively
distressing to such patients and had a negative impact on their illness. In a
retrospective longitudinal study, we investigated patients' assessment of
political change, life events that were potentially related to the political
changes, impact of the changes on subjective quality of life, and hospitalization
rates during five year periods prior to and following the change. 120 patients
with chronic schizophrenia in East Berlin and 70 in Chemnitz were examined using
quantitative and qualitative methods. Patients reported more individual freedom
and better care after 1989. They complained about stress due to loss of
employment, financial disadvantages and rising crime rates. Despite the
occurrence of potentially change-related life events after 1989, patients stated
very little impact of the changes on their illness. Retrospectively, patients in
East Berlin reported a significantly better subjective quality of life in 1994
than in 1984. Hospitalization rates did not increase after 1989. The findings are
not consistent with the hypothesis and do not suggest that political changes in
East Germany in 1989/90 had--subjectively or objectively--a substantial negative
effect on the illness of patients with chronic schizophrenia.
PMID- 11006867
TI - [Gastrointestinal oncology].
PMID- 11006868
TI - [Barrett esophagus: diagnosis and treatment].
PMID- 11006869
TI - [Gastric carcinoma].
PMID- 11006870
TI - [Gastrointestinal lymphoma: etiology, pathogenesis and therapy].
PMID- 11006871
TI - [Gallbladder and bile duct carcinoma].
PMID- 11006872
TI - [Pancreatic carcinoma].
PMID- 11006873
TI - [Colon carcinoma: early detection and endoscopic prevention].
PMID- 11006874
TI - [Primary prevention of sporadic colorectal carcinoma by diet modification and
drugs?].
PMID- 11006876
TI - [Emergencies due to drug abuse].
PMID- 11006875
TI - [Colon carcinoma. Consensus of therapeutic strategies].
PMID- 11006877
TI - [Multiple muscle abscesses in a Tibetan woman].
PMID- 11006878
TI - [Initial diagnosis of Caroli disease in a 71-year old man].
PMID- 11006879
TI - [Seeding metastasis caused by fine needle biopsy?].
PMID- 11006880
TI - [High HbA1c level in presence of good blood glucose control].
PMID- 11006881
TI - [Angiotensin-II-receptor antagonists for cardiac insufficiency].
PMID- 11006882
TI - [Peripheral neuropathy in diabetes mellitus from the perspective of internist].
PMID- 11006883
TI - [28-year old patient requiring reanimation for heart arrest after hospitalization
for deep vein thrombophlebitis].
PMID- 11006884
TI - Wall stress and the heart.
PMID- 11006885
TI - Experimental studies on myocardial stretch and ventricular arrhythmia in
hypertrophied and non-hypertrophied hearts.
AB - Hypertension affects about 5% of western populations and in the majority of cases
it is of unknown aetiology. It exposes the heart to greater levels of myocardial
stretch as a result of increased systolic pressure and peripheral resistance.
Under certain circumstances myocardial stretch may trigger arrhythmias but the
mechanisms and clinical importance of this phenomenon are unclear. This article
outlines the risks of sudden cardiac death conferred by hypertension and left
ventricular hypertrophy, presents the results of experiments using an animal
model of myocardial stretch and discusses some possible mechanisms underlying
stretch-induced arrhythmias which may be important in hypertensive patients.
PMID- 11006886
TI - Mechanoelectric coupling as a fundamental surrogate in ventricular arrhythmia?
PMID- 11006887
TI - Wall stress and hypertension.
AB - The precise role that abnormal wall stress may play in the pathophysiology of
hypertensive heart disease is not known. Hypertension is almost unique in that it
ultimately affects all parts of the law of Laplace equation, i.e.
intraventricular pressure changes and with the advent of left ventricular
hypertrophy both internal radius and wall thickness alter. If heart failure
supervenes the components of the equation change once more. This article will
discuss the implications of abnormal wall stress at these various stages in
hypertensive heart disease.
PMID- 11006888
TI - Combined seropositivity for H. pylori and C. pneumoniae is associated with age,
obesity and social factors.
AB - BACKGROUND: Manifestations of cardiovascular disease (CVD) have been associated
with chronic infection by Helicobacter pylori and Chlamydia pneumoniae both in
cross-sectional and in prospective follow-up cohort studies. This association may
be partly due to an increase in metabolic risk factors for CVD, secondary to low
grade inflammation caused by infections. OBJECTIVE: To investigate for subjects
classified according to serology titres for infection with C. pneumoniae and H.
pylori associations between seropositivity and the degree of obesity and fasting
insulin levels, as well as social factors. METHODS: Using methods based on those
in earlier investigations of hypertensive patients in the Dalby primary-health
care district, southern Sweden, we investigated frozen samples from serum of 310
middle-aged treated hypertensives and 288 age-matched and sex-matched
normotensive controls from a defined population. The baseline examination
included the measurement of weight, height and blood pressure as a mean of two
office readings with the subject supine. The body mass index (BMI) was calculated
as kg/m2. Fasting blood samples were drawn for measurements of levels of serum
lipids, blood glucose, plasma insulin and serum lipids, including total
cholesterol and triglycerides. The serology titres for H. pylori were determined
by an enzyme-linked immunosorbent assay. The titres for C. pneumoniae were
determined by a micro-immunofluorescence method. Self-reported factors concerning
social and lifestyle backgrounds were recorded. RESULTS: The group (n = 245) of
subjects with combined positive serology for H. pylori and C. pneumoniae differed
from the group without any positive serology (n = 57) in age (61.6 versus 57.4
years, P < 0.05) and BMI (27.3 versus 25.8 kg/m2, P < 0.05). The seropositive
group also differed in terms of fasting levels of insulin (12.7 versus 11.6
pmol/l, P < 0.05), but this difference did not remain significant after
adjustment for age and BMI. We detected no intergroup difference in blood
pressure and levels of glucose and lipids. Members of the group with combined
seropositivity reported having a lower social-class position (educational level)
than that of members of the seronegative group. CONCLUSION: Subjects with
combined positive serology for H. pylori and C. pneumoniae are characterized by
greater age, lower social class and higher BMI, as well as higher fasting levels
of insulin than those of seronegative subjects. Obesity might be a marker not
only for lower social class but also for greater than normal susceptibility to
such infections.
PMID- 11006889
TI - A common polymorphism in methionine synthase reductase increases risk of
premature coronary artery disease.
AB - BACKGROUND: Methionine synthase reductase (MTRR) catalyzes the regeneration of
methylcobalamin, a cofactor of methionine synthase, an enzyme essential for
maintaining adequate intracellular pools of methionine and tetrahydrofolate, as
well as for maintaining homocysteine concentrations at nontoxic levels. We
recently identified a common A-->G polymorphism at position 66 of the cDNA
sequence of MTRR; this variant was associated with a greater than normal risk for
spina bifida in the presence of low levels of cobalamin. OBJECTIVE: To
investigate whether the polymorphism was associated with alterations in levels of
homocysteine, folate, and vitamin B12, and with risk of developing premature
coronary artery disease (CAD), in a population of individuals presenting for
cardiac catheterization procedures. METHODS: We screened 180 individuals aged <
58 years with angiographically documented coronary-artery occlusions or occlusion
free major arteries for the presence of the 66A-->G MTRR polymorphism using a
polymerase-chain-reaction-based assay. RESULTS: We identified a trend in risk of
premature CAD across the genotype groups (P = 0.03) with a sex-adjusted relative
risk of premature CAD equal to 1.49 (95% confidence interval 1.10-2.03) for the
GG versus AA genotype groups. There was no difference in fasting levels of plasma
total homocysteine, serum folate, and vitamin B12 among the three MTRR genotypes.
CONCLUSIONS: Our findings suggest that the GG genotype of MTRR is a significant
risk factor for the development of premature CAD, by a mechanism independent of
the detrimental vascular effects of hyperhomocysteinemia. This association needs
to be confirmed in other studies.
PMID- 11006890
TI - Multifactorial approach to the prevention of coronary heart disease: from
computer to paper and pencil?
AB - BACKGROUND: In Europe the multifactorial clinical approach to the prevention of
coronary heart disease is based on the Framingham equation presented in graphical
form including age, sex, level of total serum cholesterol, systolic blood
pressure and smoking. OBJECTIVE: To propose a straightforward paper-and-pencil
score (Global Coronary Risk Score) including level of high-density lipoprotein
cholesterol for the Belgian or more broadly western European population derived
from 10-year follow-up mortality of a Belgian national population sample.
RESULTS: This score has the same predictive power as the Framingham equation both
for men aged 35-74 years and for women aged 50-74 years. It gives a ranking of
subjects into four groups according to their relative risks. CONCLUSION: Coronary
Risk Score is user friendly and probably has pedagogical virtues.
PMID- 11006891
TI - High prevalence of seropositivity for antibodies to Chlamydia-specific
lipopolysaccharide in patients with acute coronary syndrome.
AB - BACKGROUND: Results of recent studies have demonstrated that there is an
association between infection with Chlamydia pneumoniae and coronary artery
disease (CAD). Inflammatory response caused by chlamydial infection has been
considered to contribute to the development of atherosclerosis in coronary
arteries. OBJECTIVE: The aim of this study was to investigate the specific
relations between chlamydial infection and coronary events in patients with CAD.
METHODS: We measured serum levels of immunoglobulin A and G antibodies against
Chlamydia spp.-specific lipopolysaccharide in 155 patients with CAD and 60 age
matched and sex-matched healthy controls by enzyme-linked immunosorbent assay.
CAD patients were divided into groups of the patients with acute coronary
syndrome [(ACS), n = 35], old myocardial infarction [(OMI), n = 60] and chronic
coronary heart disease [(CCHD), n = 60]. RESULTS: Prevalence of both seropositive
antibodies in the control group and CCHD group were not different. In contrast,
in ACS group there were significantly higher prevalences of seropositive
immunoglobulin A (46 versus 12%, P = 0.0001) and G (74 versus 45%, P = 0.005)
antibodies and in OMI group there was a significantly higher prevalence of
seropositive immunoglobulin A antibodies (28 versus 12%, P = 0.02). Furthermore,
compared with CCHD group, in ACS group there were significantly higher
prevalences of seropositive immunoglobulin A (P = 0.00006) and G (P = 0.002)
antibodies and in OMI group there was a higher prevalence of seropositive
immunoglobulin A (P = 0.01). Adjustment for confounding factors did not change
these findings. CONCLUSIONS: Infection with Chlamydia is significantly associated
with ACS and OMI, but not with CCHD. These findings suggest that chronic and
reactive infection with Chlamydia can lead to disruption of vulnerable plaque in
patients with ACS.
PMID- 11006892
TI - Risk factors for atherosclerosis in young individuals.
AB - Atherosclerosis starts in childhood, and is accelerated in some individuals. A
cluster of clinical and biochemical factors constitute the risk profile for many
of them, perhaps most important being metabolic insulin resistance syndrome.
Insulin resistance and its components for children and adolescents, especially
obesity and dyslipidemia, are generators of hypertension, glucose intolerance and
complications of atherosclerosis in adulthood. Some individuals are genetically
predisposed, particularly those with the family history of such disorders. For
many subjects, there is 'tracking' of metabolic and lifestyle factors from early
age to adulthood. Several new risk factors of atherosclerosis (e.g. level of
lipoprotein (a), procoagulant state, hyperhomocysteinemia, low birth weight and
adverse in-utero environment, and possibly inflammatory markers) are current and
potentially future areas of research concerning children and young individuals.
Definition of and research on new and hitherto not investigated factors and
formulation of strategies to neutralize the known factors are of paramount
importance for primary prevention of atherosclerosis. Simple and effective
measures for prevention include increasing awareness of the diseases, maintenance
of ideal body weight, regular physical exercise, avoidance of smoking and chewing
of tobacco, eating a balanced diet, and early periodic monitoring of blood
pressure and metabolic status. These measures, starting from childhood, should be
applied to all and in particular to the susceptible offspring, predisposed
individuals, and populations.
PMID- 11006893
TI - Bibliography. Current world literature.
PMID- 11006894
TI - Hyperlipidaemia and primary prevention of coronary heart disease: are the right
patients being treated?
AB - BACKGROUND: In 1997, the Standing Medical Advisory Committee report suggested
that patients with a coronary heart disease risk of 3% per year or greater should
be considered appropriate for lipid-lowering medication. The report stated that
cholesterol concentration alone is a poor predictor of absolute risk of coronary
heart disease and recommended the Sheffield table as a method of estimating the
coronary heart disease risk. OBJECTIVE: To assess the impact of the Standing
Medical Advisory Committee report on the management of patients with
hyperlipidaemia in the primary prevention of coronary heart disease in primary
care. METHOD: A survey questionnaire giving the clinical details of 20 patients
with various coronary heart disease risk factors was sent to 200 general
practitioners in the West Midlands, UK. RESULTS: Forty-eight percent of the
respondents used clinical assessment/perception as the sole means of risk
assessment and 26% used the Sheffield table. In patients who did not require
treatment, 40.1% of the decisions were inappropriate and, in patients who
required treatment, 35.1% of the decisions were inappropriate. Overall,
inappropriate decisions were made in 37.9% of the responses. Despite the clear
advice in the Standing Medical Advisory Committee report on the importance of
incorporating multiple risk factors in estimating absolute coronary heart disease
risk, only total cholesterol and triglycerides were significant in influencing
treatment decisions. CONCLUSIONS: The Standing Medical Advisory Committee
recommendations on the management of hyperlipidaemia in primary prevention of
coronary heart disease are not widely used. Large savings could be made by
correctly identifying and treating individuals at high risk. We recommend use of
the full Framingham risk score in assessment of coronary heart disease risk in
primary care.
PMID- 11006895
TI - Re-survey of the Whitehall study of London civil servants: changes in risk
factors for cardiovascular disease during 29 years of follow-up.
AB - BACKGROUND: Substantial uncertainty persists about the relevance of blood
pressure and cholesterol to the risk of cardiovascular disease in the elderly.
OBJECTIVE: To investigate the determinants of cardiovascular risk in old age, and
the relevance of such risk factors when recorded in middle and old age. METHODS:
A re-survey in 1997 of 8537 survivors of a cohort of men who were originally
examined in 1967-1970 when aged 40-69 years. RESULTS: Completed questionnaires
were received from 7050 (82%) of the survivors, and blood pressure and blood
samples from 5427 (64%). The response rate declined with increasing age, was
inversely related to markers of socioeconomic status in 1967-70 and in 1997, and
was lower in those who had been current smokers or had a higher blood pressure
level in 1967-70. After excluding those with reported cardiovascular disease (25%
of respondents), the mean levels of total cholesterol and apolipoprotein B were
lower in older age groups, whereas apolipoprotein A1 levels did not vary much
with age. Among those with risk factors recorded both in 1967-70 and 1997, the
prevalence of smoking had declined by two-thirds (32% in 1970 and 12% in 1997),
the prevalence of diabetes had increased (0.3% versus 4.5%), and the mean
systolic blood pressure had increased by 16 mmHg (130 versus 146 mmHg), but the
diastolic blood pressure had not changed materially (80 versus 81 mmHg), and the
measured levels of total cholesterol had increased by 0.5 mmol/l (although that
change may be artefactual). CONCLUSION: Follow-up of vital status in this cohort
should permit an assessment of the relevance of risk factors recorded in middle
and old age to cardiovascular disease in old age.
PMID- 11006896
TI - Leisure-time physical activity and coronary risk factors in women.
AB - BACKGROUND: Evidence that physical activity is cardioprotective in women is not
as strong as that observed in men. Furthermore, the extent to which exercise
protects against coronary heart disease via its influence on classical risk
factors remains unclear. This study examines the relationship between reported
physical activity, a range of coronary heart disease risk factors and a 10-year
predicted coronary heart disease risk score. METHODS: A cross-sectional study of
14,077 female employees aged 30-64 years who were screened between 1988 and 1991
was employed. Measurements included systolic and diastolic blood pressure, body
mass index, serum total cholesterol, high-density lipoprotein cholesterol, total
cholesterol:high-density lipoprotein cholesterol ratio, low-density lipoprotein
cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein a
and fasting blood glucose. Participants were divided into three groups according
to reported average frequency of vigorous leisure-time physical activity, that is
zero, one to two, or three or more episodes per week. RESULTS: Increasing
activity frequency was associated with lower systolic and diastolic blood
pressure, total cholesterol, total cholesterol:high-density lipoprotein
cholesterol ratio, triglycerides and body mass index (all P < 0.001), low-density
lipoprotein cholesterol (P = 0.003), apolipoprotein B (P = 0.04) and blood
glucose (P = 0.01) and higher high-density lipoprotein cholesterol (P < 0.001)
and apolipoprotein A1 (P = 0.03). There was no association with lipoprotein a.
After controlling for possible confounders, these relationships remained
statistically significant except for apolipoprotein B and glucose. The odds
ratios for being in the top quintile of predicted 10-year coronary heart disease
risk for individuals in each category of activity were 1.0 (inactive), 0.70 (one
to two episodes of activity per week) and 0.77 (three or more episodes of
activity per week). CONCLUSION: Women engaging in vigorous, leisure-time physical
activity have a less atherogenic coronary heart disease risk factor profile than
those who do not, which translates into a potential reduction of approximately
30% in coronary heart disease risk.
PMID- 11006897
TI - Respiratory decline in smokers and ex-smokers--an independent risk factor for
cardiovascular disease and death.
AB - BACKGROUND AND OBJECTIVE: Although smoking is associated with an increased
incidence of cardiovascular disease and death, many smokers remain healthy after
many years of smoking. Our objective was to assess whether this variation is
related to rate of decline of respiratory function. DESIGN: This was a population
based cohort study, its subjects being men born in 1914 from Malmo, Sweden.
METHODS: All 291 smokers who since the baseline examination in 1969 had remained
in Malmo were invited to a follow-up examination in 1982. Of the 242
participants, 199 men without history of myocardial infarction or stroke were
included in the study. Eighty-four of them had quit smoking. The incidence of
cardiovascular disease and death during 14 years was studied in relation to the
decline in lung function [forced expiratory volume during 1 second (FEV1.0) and
vital capacity] between 55 and 68 years of age. RESULTS: Fifty-nine (51%) smokers
and 43 (51%) ex-smokers died. Forty-four (38%) smokers and 29 (35%) ex-smokers
suffered a cardiovascular event. The mortality rate among smokers in the high,
middle and low thirds with regard to the decline in FEV1.0 was 66.5, 44.0, and
37.6, respectively, per 1000 person-years (P for trend = 0.04). The corresponding
figures in ex-smokers were 88.7, 42.0, and 35.1 (P for trend = 0.002). The
cardiovascular event rate among smokers in these three groups was 56.0, 41.0, and
22.7 events, respectively, per 1000 person-years (P for trend = 0.01). The
association remained significant after adjustments for potential confounders. A
change in vital capacity was associated with a similar pattern of disease and
death. CONCLUSION: Although smoking is associated with an accelerated respiratory
decline, there are marked differences between smokers. The increased
cardiovascular event and death rates among those whose lung function declined the
most suggests that the change in respiratory function can be used as a measure of
individual susceptibility.
PMID- 11006898
TI - Work stress and coronary heart disease.
AB - BACKGROUND: Coronary heart disease (CHD) has been often regarded as a
psychosomatic illness; one of the psychosocial variables influencing the onset or
course of disease is stress. Work stress in particular may therefore be a
significant factor influencing CHD. METHOD: This descriptive review derives from
those predictive studies of work stress and CHD published from 1990-2000 based on
structured literature searches. RESULTS: There is reasonably robust and
consistent empirical evidence indicating some causal relationship between work
stress and CHD risk. CONCLUSIONS: Work stress has clear implications for the
health and welfare of employees and medico legal implications for employers.
PMID- 11006899
TI - Socioeconomic status, ABO phenotypes and risk of ischaemic heart disease: an 8
year follow-up in the Copenhagen Male Study.
AB - OBJECTIVES: The association of socioeconomic status with the risk of ischaemic
heart disease is only partly explained by the uneven distribution of conventional
risk factors. We tested the hypothesis that an uneven socioeconomic distribution
of ABO phenotypes could contribute to the explanation. DESIGN: A prospective
study controlling for age and other relevant potential confounders: smoking,
physical activity, wine consumption, height, weight, serum lipids, blood
pressure, hypertension, type II diabetes, serum selenium concentration and
soldering fumes exposure. SETTING: The Copenhagen Male Study, Denmark. STUDY
PARTICIPANTS: Two thousand, nine hundred and ninety-three men aged 53-74 years
without overt ischaemic heart disease. MAIN OUTCOME MEASURE: Incidence of
ischaemic heart disease in an 8-year follow-up. RESULTS: Two hundred and forty
two men (8.1%) had a first ischaemic heart disease event. There was no
association between socioeconomic status and the ABO blood group phenotypes and,
in accordance with this, ABO phenotype was not a confounder for the association
of socioeconomic status with the risk of ischaemic heart disease. However, ABO
blood group was a strong risk or effect modifier. Only among men with the O
phenotype was socioeconomic status (social classes IV and V versus social classes
I, II and III) associated with a significant excess risk (relative risk 1.7, 95%
confidence interval 1.1-2.7 and P = 0.02 after adjustment for confounders; the
corresponding relative risks among the A and B/AB phenotypes comparing low social
classes with the higher social classes were 1.08 (P = 0.77) and 1.08 (P = 0.89),
respectively). CONCLUSION: ABO phenotypes did not contribute directly to the
explanation of socioeconomic inequalities in the risk of ischaemic heart disease.
However, the finding of ABO phenotypes being effect modifiers for the association
of socioeconomic status with the risk of ischaemic heart disease may open up new
possibilities of clarifying the roles of socioeconomic status and ABO blood group
as cardiovascular disease risk factors.
PMID- 11006901
TI - Bibliography. Current world literature.
PMID- 11006900
TI - Plasma-induced endothelial activation associated with incident atherosclerosis:
prospective results from the Bruneck Study.
AB - BACKGROUND: Whether systemic inflammation is an epiphenomenon of atherosclerosis
or whether it is part of the atherosclerosis causal pathway requires further
study. DESIGN: As part of a prospective population survey on the course and
aetiology of atherosclerosis, we investigated the effects of plasma on the
endothelial monolayers inducing activation for leukocyte transmigration. METHODS:
An age- and sex-stratified random sample of inhabitants of Bruneck (Italy) with
and without atherosclerotic disease aged 50-69 years was selected. Carotid
arteries were evaluated by duplex sonography at baseline (1990). Carotid arteries
were re-evaluated for the development of new plaques 5 years later (1995). Frozen
plasma samples from baseline were available for a random sample of 152 men.
Monolayers of endothelial cells cultured in micropore filter insets were pre
treated with plasma, then normal human neutrophils were added to the endothelial
cells and subsequent transmigration through the monolayers and micropore filters
was measured. RESULTS: The endothelial monolayers were activated for
transmigration of leukocytes more potently by plasma from participants with
carotid artery plaques than participants without it. Increased endothelial
activation with plasma at baseline was associated with the development of new
atherosclerotic lesions during a period of 5 years. CONCLUSIONS: Plasma from
individuals with prevalent atherosclerosis of the carotid arteries activates the
endothelium for leukocyte transmigration, suggesting the presence of systemic pro
inflammatory mediators. In an epidemiological survey, follow-up data on new
lesion formation after 5 years indicated that plasma-mediated endothelium
activation for interaction with leukocytes precedes the development of
atherosclerotic lesions.
PMID- 11006902
TI - Music perception and octave generalization in rhesus monkeys.
AB - Two rhesus monkeys were tested for octave generalization in 8 experiments by
transposing 6- and 7-note musical passages by an octave and requiring same or
different judgments. The monkeys showed no octave generalization to random
synthetic melodies, atonal melodies, or individual notes. They did show complete
octave generalization to childhood songs (e.g., "Happy Birthday") and tonal
melodies (from a tonality algorithm). Octave generalization was equally strong
for 2-octave transpositions but not for 0.5- or 1.5-octave transpositions of
childhood songs. These results combine to show that tonal melodies form musical
gestalts for monkeys, as they do for humans, and retain their identity when
transposed with whole octaves so that chroma (key) is preserved. This conclusion
implicates similar transduction, storage, processing, and relational memory of
musical passages in monkeys and humans and has implications for nature-nurture
origins of music perception.
PMID- 11006903
TI - Switching tasks and attention policies.
AB - The determinants and costs of control were studied in 6 experiments examining the
performance costs of changing stimulus dimension (digit value/number of elements)
or attention strategies (speed/accuracy) on the first trial after task
transition. Costs were compared for task shift and reconsideration only.
Preparation ability was studied by presenting all transition information at the
beginning of a 2-part block or only prior to each part. Results showed pronounced
first-trial transition costs. Different factors were associated with stop-start
and task-switching requirements. Transition costs were separate from those of
basic task performance. Costs were sensitive to global control considerations and
were larger for task dimension changes than for attention strategy shifts. Costs
involving task dimension change, but not strategy shifts, were reduced with
advanced preparation. These results are discussed in relation to contemporary
models of control. A new distinction is proposed between activation and execution
of control strategies.
PMID- 11006904
TI - The task dependence of staged versus cascaded processing: an empirical and
computational study of Stroop interference in speech production.
AB - The authors investigated the on-line relationship between overt articulation and
the central processes of speech production. In 2 experiments manipulating the
timing of Stroop interference in color naming, the authors found that naming
behavior can shift between exhibiting a staged or cascaded mode of processing,
depending on task demands: An effect of Stroop interference on naming durations
arose only when there was increased pressure for speeded responding. In a simple
connectionist model of information processing applied to color naming, the
authors accounted for the current results by manipulating a single parameter,
termed "gain," modulating the rate of information accrual within the network.
Results are discussed in relation to mechanisms of strategic control and the link
between cognition and action.
PMID- 11006905
TI - Language-dependent recall of autobiographical memories.
AB - Two studies of autobiographical memory explored the hypothesis that memories
become more accessible when the linguistic environment at retrieval matches the
linguistic environment at encoding. In Experiment 1, Russian-English bilinguals
were asked to recall specific life experiences in response to word prompts. The
results supported the hypothesis of language-dependent recall: Participants
retrieved more experiences from the Russian-speaking period of their lives when
interviewed in Russian and more experiences from the English-speaking period of
their lives when interviewed in English. In Experiment 2, the language of the
interview was varied independently from the language of the word prompts. Both
variables were found to influence autobiographical recall. These findings show
that language at the time of retrieval, like other forms of context, plays a
significant role in determining what will be remembered.
PMID- 11006906
TI - Color categories are not universal: replications and new evidence from a stone
age culture.
AB - The authors sought to replicate and extend the work of E. Rosch Heider (1972) on
the Dani with a comparable group from Papua, New Guinea, who speak Berinmo, which
has 5 basic color terms. Naming and memory for highly saturated focal, non-focal,
and low-saturation stimuli from around the color space were investigated.
Recognition of desaturated colors was affected by color vocabulary. When response
bias was controlled, there was no recognition advantage for focal stimuli. Paired
associate learning also failed to show an advantage for focal stimuli.
Categorical Perception effects for both English and Berinmo were found, but only
at the boundaries of existing linguistic categories. It is concluded that
possession of linguistic categories facilitates recognition and influences
perceptual judgments.
PMID- 11006907
TI - A sampling approach to biases in conditional probability judgments: beyond base
rate neglect and statistical format.
AB - Conditional probability judgments of rare events are often inflated. Early
accounts assumed a general deficit in using statistical base rates. More recent
approaches predict improvement when problems are presented in frequency format or
refer to natural categories. The present theory focuses on sampling processes.
Experiment 1 showed that a seeming advantage of frequency over probability
formats is due to a confounded factor, the need to mentally transform stimulus
samples. An information search paradigm was used in Experiment 2. When sampling
by the predictor, the probability to be estimated, p(criterion/predictor), was
conserved in the samples and judgments were quite accurate. However, when
sampling by the criterion, the low base-rate event was strongly overrepresented,
accounting for the entire bias. Judgments were quite sensitive to the sampled
data, but failed to take sampling constraints into account, as shown in
Experiments 3 and 4.
PMID- 11006908
TI - [Hearing screening in newborn infants. Comparative studies and cost analysis with
different instruments].
AB - BACKGROUND: The necessity of screening examinations in newborns today cannot be
denied. Up to now, it has only been achieved in a few countries to introduce a
general hearing screening for newborns. METHODS: We examined 100 newborns (200
ears) at their third day of life. All ears were evaluated with the TEOAE
screening-device ECHOSCREEN. In addition, we carried out BERA screening
examinations with the ALGO PORTABLE or with the EVOFLASH on 100 of these 200
ears. As a reference method, we utilized TEOAE-examinations with the ILO-88 for
all ears. RESULTS: 4.5% of the 200 ears examined with the ECHOSCREEN were
conspicuous due to accumulation of earwax problems. With the ALGO-system, none of
the ears was conspicuous. Among the 100 ears examined with the EVOFLASH we found
negative results with seven ears (4 children). These findings will be discussed
in detail. Furthermore, we analyzed the costs for one-step- and two-step
screenings. Costs for a one-step-screening of both ears would be DM 14.27 with
Echoscreen, DM 44.69 with ALGO, DM 32.19 with Evoflash for one patient including
material and personnel costs. Costs for a two-step-screening would be DM 16.28
with Echoscreen and ALGO, DM 15.72 with Echoscreen and Evoflash, calculated per
child on the basis of 812,173 newborn children in the year 1997 in Germany.
CONCLUSION: On the basis of all these results, we recommend a two-step-screening
with TEOAE and BERA-devices.
PMID- 11006909
TI - ["Vibrant Soundbridge" middle ear implant for auditory rehabilitation in sensory
hearing loss. I. Clinical aspects, indications and initial results].
AB - BACKGROUND: The adequate therapy for patients suffering from a sensory hearing
loss consists of fitting electronic hearing devices. Conventional hearing aids,
however, present with significant inherent drawbacks such as insufficient
amplification in the high frequency range, problems with the ear mold (feed back,
occlusion, external otitis), or distortion of sound with an "unnatural" hearing
impression. METHODS: The partially implantable middle ear device Vibrant
Soundbridge provides a sound wave conversion into mechanical vibrations at the
middle ear ossicles using the Floating Mass Transducer (FMT). The audiological
advantages are due to a direct moving force to the perilymph via incus and
stapes. The Vibrant Soundbridge system is indicated in patients with a medium to
severe symmetrical sensory hearing loss and a normal middle ear. Candidates need
previous experience with conventional hearing aids without satisfactory results.
RESULTS: The eight operated patients report a "natural" quality of sound and
speech, a better hearing perception at high frequencies and the absence of feed
back phenomena. Audiological evaluation and questionnair results support the
patients subjective hearing impression. CONCLUSIONS: The Vibrant Soundbridge
improves hearing quality in patients with sensory hearing loss. The hearing
implant is indicated in particular in patients that are unable to wear
conventional hearing aids.
PMID- 11006910
TI - [Studies of the histomorphology and function of the uvula].
AB - BACKGROUND: Alternations in pharyngeal structure and function are considered
fundamental in the pathogenesis of snoring or obstructive sleep apnea (OSA). The
physiological function of the uvula as a dynamic sealing of the nasopharynx
prevents a "craniocaudal aspiration" during deglutition. The oropharyngeal soft
tissues and the uvula are known to play an important role in affecting the
oropharyngeal airflow resistance but studies about alterations in the
histomorphological uvula structure are controversial. METHODS: We studied the
histomorphological tissue composition of the uvula (midsagittal and transversal
sections) in 142 patients who underwent uvulopalatopharyngoplasty (UPPP) or
uvulopalatoplasty (UPP) for snoring and by autopsy in 30 normal subjects not
known to have been snoring. Statistical comparisons were controlled for
differences caused by age and body mass index. RESULTS: The uvula was found to be
significantly longer in patients with snoring than in control subjects. Patients
with snoring had a significantly greater percentage of fat content and connective
tissue in combination with a muscle atrophy in the uvula than did normal
subjects. CONCLUSIONS: The disturbance of the specific muscular composition and
formation causes a reduction of muscular tonus and a loss of muscular
contraction. The uvula is destabilized on the basis of a missing skeletal and
cartilaginous brace. The uvula destabilization causes a narrowing of the
pharyngeal airway that could lead to an increased oropharyngeal airflow
resistance with an intensified passive uvula movement and vibration during mouth
breathing.
PMID- 11006911
TI - [Parotid involvement in cat scratch disease: a differential diagnosis with
increased significance].
AB - BACKGROUND: Bartonella henselae is the causative agent of cat-scratch disease
(CSD), an inflammatory infection of the lymph nodes. So far, only few cases of
atypical manifestations in the head and neck, especially manifestations in the
parotid gland have been reported. PATIENTS AND METHODS: Between January 1997 and
June 1999 seven patients with manifestations of CSD in the parotid gland were
observed at the ENT-department Freiburg. The positive diagnosis was confirmed
serologically by an indirect immunofluorescence assay and by detection of
Bartonella henselae-DNA with PCR-amplification and subsequent hybridization or
sequencing. RESULTS: An intraglandular abscessed lymphadenitis was found in five
patients, two of these cases were based on a Parinaud's oculoglandular syndrome.
A diffuse affection of the parotid gland, initially misinterpreted as a parotid
tumor, was seen in two patients. CONCLUSIONS: Antibiotic treatment is recommended
in order to reduce the duration of the disease, in cases of pain and lymph node
abscesses. In uncommon manifestations of CSD, the nosological assignment can be
difficult on the basis of the heterogeneous symptomatic in the individual patient
and the CSD diagnosis can only be confirmed by serology or PCR-based techniques.
CSD should be considered in the differential diagnosis of all equivocal masses in
the head and neck, even in unusual localisations like the parotid gland.
PMID- 11006912
TI - [Second carcinomas in cancers of the mouth cavity, pharynx and larynx. Clinical,
histopathologic and cell kinetic findings].
AB - BACKGROUND: The mortality because of malicious tumours of the oral cavity, of the
pharynx and of the larynx has considerably increased in the Federal Republic of
Germany during the last two decades. The prognosis not only shows a high ratio of
recidivations and formation of metastases, but also a typical field canceration.
There is a high rate of incidence of multiple primary, resp. secondary tumours
that may occur synchronously or metachronously. Up to now we have learnt only
little about the mechanisms concerning the development of tumours and their
spread on the cellular molecular level. METHOD: The subject of the present
retrospective study was the analysis of patients suffering from an epithelioma of
the oral cavity, the pharynx and the larynx and the following secondary
carcinomatas. The control group were patients suffering from primary tumours of
the same location and subsequent recidivation or metachronous metastasis. By
determination of the degree of malignity and keratinisation of the DNA ploidy, of
the immunohistological expression of p53 and the immunohistological proliferation
marker MIB1 conclusions had to be drawn with regard to the biological behaviour
of tumours. RESULTS: The evaluation of the clinical parameters of the 122
patients on the whole revealed a clear increase of new disease as well as a
shifting to the younger age within the last five years. Surprisingly, most common
were secondary tumours in case of larynx carcinomatas. Patients suffering from
secondary tumours show a bad prognosis, however, their maximum survival does not
differ considerably from that of patients suffering from recidivations, resp.
metastases. Because of the early diagnosis of the secondary carcinomatas the
prognosis will depend on the primary carcinoma in most of the cases. The
prognosis data indicate that independently from the fact whether there is a
primary or a subsequent tumour, the therapy to be applied can only be a combined
therapy consisting of operation and ray-therapy. The present examinations confirm
reports with regard to disturbance of the p53 regulation that also play an
important role in case of the head-neck area. The parallel analysis of MIB1 as a
proliferation marker showed in case of the primary carcinomatas a correlation of
positive p53-immunocolour with moderate and strong proliferation. Tumours in the
hypopharynx and larynx showed a significantly smaller proliferation than that of
the oral cavity and oropharynx. In case of the primary and secondary tumours the
proliferation is more common in case of the G3-tumours. CONCLUSIONS: The in total
modest differences between the primary and secondary carcinoma with regard to the
DNA-ploidy; the proliferation and the p53-expression presumably originate in
their formation within the scope of a so-called field canceration. Because of the
field canceration supposed for the mucous membranes of the upper aerodigestive
tract, the check-ups of these patients performed in regular intervals must not be
limited in any case to the area of the primary tumour. They will have to consider
the entire visible area of the upper respiratory and esophageal tract.
PMID- 11006913
TI - [Lymph node metastases in the neck of unknown primary tumor].
AB - BACKGROUND: Cervical lymph nodes represent the most frequent manifestation of
lymph node metastases of unknown primary. Nearly 3% of all malignant ENT-tumors
are cervical lymph nodes metastases of unknown primary. This disease is a
challenge for clinical working physician in diagnosis and therapy. MATERIAL AND
METHOD: In a retrospective study we investigated 99 patients with the diagnosis
cervical lymph node metastases of unknown primary, which were treated and
observed in our department between 1975 and 1995. Within this group we observed
the course of 83 patients completely. RESULTS AND CONCLUSIONS: The tumor
dependent 5 year-survival-rate was 11%. This is very low, but similar to the
literature. 40% of patients, that were operated on neck dissection with or
without postoperative irradiation survived tumor-dependent 5 years. In 42 cases
we could find a primary tumor. 14 of these primaries were located in the upper
aero-digestive-tract, 28 in other regions of the body. The identification of the
primary did not improve the prognosis of the patients. A good prognosis was
associated with further occult primary, location of the lymph nodes in the upper
or middle level of the neck or parotid region and a histology of squamous cell or
undifferentiated carcinoma. Signs of poor prognosis were metastasis in the
supraclavicular region, of adenocarcinoma and inoperability of the lymph node.
The combination therapy of neck dissection and irradiation proved to be best. The
extended field radiation of the complete upper aero-digestive-tract did not cause
a improvement of tumor-dependent 5-year-survival. We discovered a primary in 5 of
27 patients in this group within the irradiated area. In conclusion extended
field radiation must be discussed critically for patients with lymph node
metastasis of unknown primary.
PMID- 11006915
TI - [Interesting case no. 37. Jaffe-Lichtenstein fibrous dysplasia (osteodystrophia
fibrosa)].
PMID- 11006914
TI - [Median sagittal mandibulotomy in head-neck tumors].
AB - BACKGROUND: Histologically proven radical resections are the goal in patients
with head and neck cancer because of improved survival rates. The frequency of
histologically radical resections using the median mandibulotomy and the
morbidity of this approach for tumors of the oropharynx and the parapharyngeal
space are described in a patients series. METHODS: The follow-up includes 16
consecutive patients who were operated on by a median mandibulotomy approach
between 1995 and 1998. The oncological benefit (tumor free margins),
complications and the functional results (ability of opening the mouth
mastication, swallowing, speech, cosmesis and pain) were reviewed. RESULTS: In
15/16 cases a histological radical resection was achieved. 14 patients were
irradiated postoperatively. In this group 3 patients had an osteoradionecrosis,
one an osteomyelitis of the mandible. The functional results were worse in more
advanced tumors. CONCLUSION: The indications for a median mandibulotomy are
primarily T3 and T4 tumors of the oral cavity and oropharynx, rarely expansive
benign parapharyngeal tumors. In most cases a histological radical resection is
achieved even in advanced tumors, probably due to the wide exposure of the
involved area. In contrast this approach is associated with a high morbidity.
PMID- 11006916
TI - [Plastic surgery reconstructions in the neck area. Superficial neck soft tissue
skin loss II].
PMID- 11006917
TI - Beyond the UKPDS: in search of the optimal strategy for the treatment of type 2
diabetes.
PMID- 11006918
TI - Clinical effects of virgin olive oil polyphenols: between myth and reality.
PMID- 11006919
TI - Evidence of postprandial absorption of olive oil phenols in humans.
AB - BACKGROUND AND AIM: Olive oil phenols are potent antioxidants in vitro. If this
were to be also demonstrated in vivo, it would help to explain the beneficial
effects of this typical ingredient of the Mediterranean diet. This study was
designed to determine the presence in lipoprotein fractions of two phenolic
compounds peculiar to extra virgin olive oil, namely tyrosol and OH-tyrosol, and
whether their absorption induces an antioxidant effect in vivo. METHODS AND
RESULTS: Two trials were performed. In the first (Long-term), 14 healthy
volunteers followed two diets, each for one month. The only difference between
the diets was that the first supplied 50 g of extra virgin olive oil per day,
where-as the second one supplied 50 g of refined olive oil with no simple
phenols, as demonstrated by GC-MS analysis. There were no changes in LDL
oxidizability and tyrosol and OH-tyrosol were not recovered in lipoproteins and
plasma from fasting samples drawn at the end of each diet period. In the second
study (Postprandial), eight healthy volunteers received an oral fat load
consisting of 100 g of extra virgin olive oil. Blood was drawn at times 0', 30',
60', 120', 240', 360', and major plasma lipoprotein classes were separated. The
concentration of tyrosol, OH-tyrosol and vitamin E was determined in lipoprotein
fractions. Plasma antioxidant capacity was measured by a crocin-bleaching test
and expressed as mM Trolox C equivalents. Tyrosol and OH-tyrosol were recovered
in all lipoprotein fractions, except VLDL, with concentrations peaking between
60' and 120'. However, a very high variability in tyrosol and OH-tyrosol
absorption was observed among subjects. Vitamin E content of LDL and HDL did not
vary significantly throughout the study. Plasma antioxidant capacity increased
significantly at time 120' (baseline 0.96 mM Trolox; 120' 1.19 mM Trolox; p =
0.02), and then returned almost to baseline values after 360' (1.1 mM Trolox).
CONCLUSIONS: These findings suggest that phenolic compounds in olive oil are
absorbed from the intestine, though not through a pathway dependent on
chylomicron formation, and may exert a significant antioxidant effect in vivo,
probably in the postprandial phase.
PMID- 11006920
TI - The fatty acid composition of chylomicrons influences the rate of their lipolysis
in vivo.
AB - BACKGROUND AND AIMS: Previous work in our laboratory has shown that chylomicron
triacylglycerol is lipolysed in vitro by lipoprotein lipase more rapidly when the
particles are enriched with n-6 polyunsaturated as compared to saturated,
monounsaturated or n-3 polyunsaturated fatty acids. It is possible, however, that
this does not reflect the situation in vivo, where the active enzyme is bound to
the vascular endothelium. The aim of the present study is to investigate the
effect of the fatty acid composition of chylomicrons on their lipolysis in the
rat in vivo. METHODS AND RESULTS: [3H]Oleate-labelled chylomicrons derived from
palm, olive, corn or fish oil (enriched in saturated, monounsaturated, n-6
polyunsaturated and n-3 polyunsaturated fatty acids respectively) containing >
90% of the label in triacylglycerol were injected intravenously into functionally
hepatectomised rats and blood samples were taken at time intervals up to 40 min.
The radioactivity in serum triacylglycerol decreased significantly more rapidly
when corn oil as compared to palm, olive or fish oil chylomicrons were used.
Conversely, the radioactivity in serum free fatty acid derived from corn oil
chylomicrons showed a faster increase than that derived from the other three
types of particles. CONCLUSIONS: These results indicate that chylomicrons
enriched with n-6 polyunsaturated fatty acids are converted to chylomicron
remnants in vivo more rapidly than those enriched with saturated, monounsaturated
or n-3 polyunsaturated fatty acids. This provides a partial explanation for the
differential rate of removal from the blood of cholesterol carried in
chylomicrons of different fatty acid composition demonstrated in previous work
from this laboratory.
PMID- 11006922
TI - Complement activation in hypercholesterolemia.
AB - BACKGROUND AND AIM: Inflammatory and lipid factors share an important role in
atherosclerosis. This study evaluates their relations in dyslipidemic subjects.
METHODS AND RESULTS: We compared the complement system (serum hemolytic activity
CH50, C3 and C4 fractions and terminal complex sC5b-9) in 30 hypercholesterolemic
patients with elevated cholesterol and decreased HDL-cholesterol levels, 30
normolipemic patients with clinical atherosclerosis and 30 matched normal
subjects. In addition we evaluated the circulating immune complexes containing
cholesterol (chol-CIC) on the assumption that they might be important in
complement activation, and the circulating levels of the adhesion molecule ICAM-1
(sICAM-1) as a sign of endhotelial dysfunction. We found a significant increase
of sC5b-9 (but not of CH50 and C3, C4) in the hypercholesterolemics compared with
the other groups. The plasma sC5b-9 level was inversely and significantly related
to HDL-chol (regression analysis), whereas no direct significant relation was
found between sC5b-9 and cholesterol. Chol-CIC were also significantly increased
in this group. The atherosclerosis patients also presented a significant increase
of sC5b-9. Lastly, both patient groups displayed a significant increase of sICAM
1. CONCLUSIONS: We suggest that complement activation in dyslipidemics may be
induced by their increased immune complexes. However, the decrease of complement
regulatory proteins carried by HDL is another important factor, while complement
changes may be related to variations of other humoral and cell systems
(endothelium, coagulative/fibrinolytic system), whose involvement is suggested in
our study by the changes of sICAM-1.
PMID- 11006921
TI - Dietary fatty acid composition influences the degree of human LDL oxidation, but
has only minor effects on vascular tone in a bioassay system.
AB - BACKGROUND AND AIM: Oxidized LDL has been detected in atherosclerotic vessels and
presumed to be one of the major risk factors in atherosclerosis and
cardiovascular diseases. The aims of the present study were to clarify whether
the oxidation degree of LDL influences arterial tone and whether different long
lasting dietary habits have effects on biological variables. METHODS AND RESULTS:
The lag phase of LDL oxidation was shorter (117 +/- 6 min) in the fish diet group
than in the vegetarian (153 +/- 5 min) or the control diet group (152 +/- 10
min). The rat mesenteric arterial rings, which were preincubated with LDL
oxidized to 1-30%, from the vegetarian and the fish diet groups showed (p < 0.05)
decreased NA-induced maximal contraction forces when compared to the control
diet. The LDL oxidation degrees of 31-60% and 61-90% had no effect on NA- and KCl
induced maximal contraction forces when compared to native LDL, nor were there
differences between the diet groups. Endothelium-dependent and independent
relaxation responses behaved similarly in all groups and were independent of the
degree of oxidation. CONCLUSIONS: Dietary habits change the fatty acid
composition of LDL, but have only minor effects on the vasoactive properties of
oxidized LDL.
PMID- 11006923
TI - Primary prevention of coronary heart disease: from controversy to consensus.
AB - In recent years, interest has tended to focus on prevention of coronary events in
high-risk groups, particularly those with established coronary heart disease.
While this is understandable, it has led to a lack of emphasis on primary
prevention. Yet it is only by means of primary or even pri-mordial prevention
that a substantial reduction in coronary mortality on a population level will be
achieved. This becomes clear when we consider that half of all persons who suffer
a first myocardial infarction will die within the first month thereafter.
Nevertheless, major progress has been made in primary prevention. Reliable risk
algorithms have been constructed in Europe (PROCAM) and the U.S., and preliminary
analyses on both sides of the Atlantic indicate that these algorithms can be
useful applied to populations which are geographically and ethnically distinct
from those in which they were derived. A notable trend in recent years is the
increasing recognition of the metabolic syndrome with its key components of
abdominal obesity, hypertriglyceridemia hypertension, low HDL-C, small, dense
LDL, insulin resistance and hyperinsulinemia as being perhaps the most common and
dangerous metabolic abnormality of all. Newer risk markers are being evaluated.
The position of homocysteine remains unclear. Despite a strong association of
elevated homocysteine with risk in case-control studies, prospective
investigations have been less convincing. Evidence is beginning to accumulate
from cross-sectional and prospective studies that markers of inflammation such as
C-reactive peptide may improve our ability to predict risk of coronary events.
While these data are encouraging, results of further studies must be awaited
before the true place of these markers can be determined. The same can be said of
many genetic markers of risk. Though a very large number of association studies
have indicated links between a variety of genetic markers and coronary risk,
these effects have tended to disappear after controlling for epigenetic and
confounding factors and with increasing sample sizes. Finally, much attention is
being devoted to non-invasive imaging of the coronary arteries. Such methods hold
much promise as a screening test to exclude coronary stenosis in low-risk
individuals. However, the measurement of calcium content of the arterial wall by
EBCT has yet to prove its usefulness as a predictor of coronary events.
PMID- 11006924
TI - Phyto-oestrogens and cardiovascular disease risk.
AB - AIM: To present the currently available evidence on the cardiovascular benefits
and risks associated with phyto-oestrogens. DATA-SYNTHESIS: Medline search from
1966-1999 updated with cross-check of references of papers with keywords such as
phyto-oestrogens, isoflavones, lignans, genistein, daidzein, enterolactone,
enterodiol, cardiovascular disease, cardiovascular disease risk factors.
CONCLUSIONS: Phyto-oestrogens are plant chemicals divided into three main
classes: isoflavones, coumestans, and lignans that display oestrogen-like
activity due to their ability to bind to the oestrogen receptor. They are found
in grains, beans, green vegetables, fruits, nuts, and grasses. Isoflavones are
primarily found in soybeans and soy foods. For epidemiological studies of the
relation between phyto-oestrogen intake and disease parameters, intake is
estimated with several measures, such as biomarkers (concentrations in urine or
blood) or dietary questionnaires, though the optimal method is not yet clear.
Phyto-oestrogens are considered to act as selective oestrogen receptor modulators
(SERM), exerting both oestrogen agonist and antagonist action. Supplementation
with isolated soy protein containing the isoflavones genistein and daidzein
reduces serum total and LDL-cholesterol and triglycerides in animals and in
humans. Vascular reactivity might be improved by supplementation with isolated
soy protein or isoflavones isolated from red clover. Studies on atherosclerosis
in animals indicate a potential for risk reduction. Evidence in humans is still
scanty. The little we know of the effects of regular dietary phyto-oestrogen
intake comes from studies in which phyto-oestrogens were added to the usual diet.
Most supplementation studies have been conducted with soy isoflavones, whereas
the importance of lignans has not been determined, though they could be more
important sources than isoflavones in Western populations. Research has been
focused on risk factors. Studies of clinically manifest endpoints are urgently
needed.
PMID- 11006925
TI - The salt epidemic: old and new concerns.
AB - Salt is the most suspected environmental factor which may influence arterial
pressure. The recent demonstration that in the chimpanzee there is a strict dose
response relationship between salt added to food and arterial pressure and that
the large majority of these animals are "salt-sensitive" is solid proof that salt
has a central importance in arterial hypertension. The behavioral complexity of
mankind is such that the issue of salt sensitivity is very difficult to study in
man. This is probably the main reason why all attempts to validate the arterial
pressure response to tests of salt sensitivity based on changes in salt intake
have produced negative or inconclusive results. However our inability to reliably
identify salt-sensitive individuals in no way implies that the pressor effect of
salt is evenly distributed in the population or that it is intrinsically so
variable that the scientific efforts aimed at defining its nature are bound to
fail. We envisage that in the near future the individual "salt-sensitive risk
profile" will be calculated on the basis of new scientific knowledge about
hypertension genes and environmental risk factors influencing the pressor
response to salt. The link between target organ damage and salt is even stronger
than that between arterial pressure and salt. Left ventricular mass is closely
related to salt intake. In the kidney there is evidence that high salt intake
induces hyperfiltration and raises glomerular pressure. Of note the damaging
potential of salt to the heart and the kidney seems to be largely independent of
the ongoing arterial pressure response. A widespread reduction in salt intake at
population level might in theory produce major health benefits but it seems
unlikely that major public health actions will be undertaken in the near future.
PMID- 11006926
TI - [The pathologist as a discover of patterns. Perspectives in disease morphology].
PMID- 11006927
TI - [History of histopathology].
PMID- 11006928
TI - [Pituitary necrosis. Decreasing incidence due to modern intensive therapy?].
AB - Pituitary necroses develop from the interruption of circulation in the pituitary
stalk, especially due to shock, trauma, etc. We studied the incidence, extent,
and outcome of necroses in postmortem series from 1991 to 1998 and compared these
with the findings in our own study in the 1970s. Necroses were classified into
four degrees based on the proportion of anterior pituitary volume: grade I, up to
5%; grade II, 5-10%; grade III, 10-50%; grade IV, more than 50%. The data show a
decreased incidence of necrosis, from 7.7% in the 1970s to 3.1% in the 1990s.
Scars, indicating former necroses, decreased in incidence from 11.4% to 3.6%. The
changes in the four grades of necrosis were: a decrease in grade I from 60% to
41%, a decrease in grade II from 24% to 22%, an increase in grade III from 9% to
17%, and an increase in IV from 8% to 20%. These figures reveal that pituitary
necroses became less frequent but more extensive. Necroses of grade IV are
generally caused by more than a single cause. The decreased incidence appears to
be the consequence of progress in intensive care over the past 20 years, as
patients can now survive severe shock longer. The increased frequency of
intensive necroses is probably due to the longer period for greater extent of
necrosis to develop during intensive care.
PMID- 11006929
TI - [Diagnostic importance of flow cytometry in staging malignant lymphoma].
AB - Bone marrow biopsy plays an important role in the clinical diagnosis of malignant
lymphoma. Further diagnostic methods need to be established to increase accuracy
in the light of advances over recent years in the immunophenotypical
characterization of discrete lymphatic bone marrow lesions and the continuing
difficulty in classifying them. This study compared the diagnostic value of flow
cytometry to that of conventional bone marrow biopsy in 156 patients with 191
marrow biopsy specimens or bone marrow aspirates. The most important findings
were that up to one-third of lymphomas could not be diagnosed by flow cytometry,
and that the degree of infiltration was estimated as less than two-thirds.
However, flow cytometric results were more satisfactory in acute lymphoblastic
leukemia, lymphoblastic lymphoma, hairy cell leukemia, and chronic lymphocytic
leukemia. In summary, flow cytometry has a complementary role in the staging of
lymphoma but cannot fully replace conventional trephine biopsy.
PMID- 11006930
TI - [Spontaneous complete rupture of a thrombotic aneurysm of the tibiofibular
trunk].
AB - True arterial aneurysms of the infrapopliteal vessels are a rare finding. During
surgical treatment of convergent aneurysms of the popliteal artery and the
tibiofibular trunk we discovered a complete spontaneous rupture of the thrombotic
aneurysm of the right tibiofibular trunk. We describe the special features of
diagnosis, histology, and the surgical treatment of aneurysms of the crural
arteries. We recommend that even asymptomatic aneurysms be electively operated on
to prevent further complications.
PMID- 11006931
TI - [Acardius or "twin-reversed arterial prefusion" sequence. Report of four cases
and review of current therapeutic possibilities].
AB - We describe four cases of acardius (one of hemiacardius, two of holoacardius
acephalus, and one of the holacardius amorphus) and present the current range of
therapeutic possibilities: control of amniotic fluid by repeated amniocentesis or
indomethacin therapy, administration of digoxin to the mother, selective preterm
delivery of the acardiac twin by hysterotomy, interruption of the anastomoses by
injection of thrombogenic coils, sclerosing agents, umbilical cord ligation,
fetoscopic laser coagulation, and thermocoagulation.
PMID- 11006932
TI - [Serous cystadenofibroma of the epiploic appendix. A tumor of the secondary
mullerian system: case report and review of the literature].
AB - We present a case of serous cystadenofibroma 2 cm in diameter in the epiploic
appendix of the sigmoid as incidental finding in a 72-year-old patient who
underwent hysterectomy and oophorectomy for endometrial carcinoma. The tumor
showed the same histology as analogous tumors of the ovary and was associated
with endosalpingiosis. Further findings were large adhesions between the epiploic
appendices of the sigmoid and the parietal peritoneum and atypical cells in the
peritoneal washings. Both may be explained by occult peritoneal endosalpingiosis.
The histogenesis, histology, and locations of extraovarian mullerian tumors are
reviewed.
PMID- 11006933
TI - [Sudden cardiac death during sports due to coronariitis].
AB - A case of sudden and unexpected death of a 29-year-old man during a basketball
game is reported. Six years before death a transient ischemic attack and a
membranous glomerulonephritis were diagnosed. The autopsy revealed as cause of
death to be a severe lymphoplasmocytic coronariitis and, in addition, a small
single focus of a lymphoplasmocytic aortitis, indicating a systemic disease. A
suspected syphilitic vasculitis could not be confirmed. In the literature there
are few cases of similar coronary arteriitis are described, such as Takayasu's
type of arteriitis in men of young and middle age.
PMID- 11006934
TI - [Endemic syphilis in the recognized relics..... Letter to Der Pathologe (5/99)
20:292-296].
PMID- 11006935
TI - [In Process Citation]
PMID- 11006936
TI - [Bone marrow involvement in hematologic neoplasms and solid tumors].
AB - Bone marrow involvement is often observed in patients with hematological
malignancies and solid tumors. Sensitive immunological and molecular biological
methods allow the detection of isolated transformed cells in bone marrow samples.
Like normal hematopoietic cells, tumor cells interact with bone marrow stroma
through adhesion molecules. Since adhesion molecules play an essential role in
the invasion and proliferation of malignant cells, new therapeutic approaches
involving the inhibition of cell-cell and cell-matrix interactions are
conceivable.
PMID- 11006937
TI - [Micrometastatic cells in the bone marrow of patients with breast carcinoma].
AB - BACKGROUND: The immunocytological detection of disseminated epithelial cells in
bone marrow in patients with breast cancer has been performed at many hospitals
and institutes since the early 1980s. Despite numerous publications in this
field, it has not been possible to standardize the method and establish the ideal
antibody, either nationally or internationally. Molecular biological methods
using PCR technology could extend the diagnostic spectrum. However, one of the
major problems in breast cancer is the lack of a disease-specific marker gene. As
a result, immunocytology is still the standard procedure for tumour cell
detection. METHODS: The detection of disseminated single cells in bone marrow in
primary breast cancer (also known as minimal residual disease) is a new
prognostic factor for disease-free and overall survival. This has been
demonstrated in three large (N > 300) groups and several small to medium groups
(N = 50-300). As a marker of dissemination in a target organ for metastasis this
prognostic factor corresponds much more closely to the tendency of breast cancer
to early haematogenic spread. Tumour cell detection may predict the course of the
disease better than the axillary lymph node status. Bone marrow aspiration and
detection of disseminated cells might replace lymph node dissection, at least in
those patients with small tumours and no clinical signs of lymph node
involvement. This strategy will soon be investigated in appropriate studies.
Another possible clinical use might be deciding on whether or not to give
adjuvant systemic therapy to node-negative patients. Patients with positive
tumour cell detection are at a higher risk of subsequent metastasis, even if the
axillary nodes are histologically normal. APPLICATION OF METHODS: The
immunohistological or molecular biological detection of tumour cells in axillary
lymph nodes might also be very useful, now that is has been shown that a
considerable subset of patients determined to be node-negative by means of
conventional methods, are positive according to these new techniques. These
methods could be a useful supplement to sentinel node biopsy. A further potential
use of this method is in monitoring therapy with new treatment modalities such as
gene therapy and immunotherapy. Repeated bone marrow aspiration can provide
information on the success of therapy in minimal residual disease
(cytoreduction). Immunocytochemical investigation of individual cells may be
useful in studying the pathogenesis of metastasis, in particular in the skeleton.
Phenotyping of cells might allow statements to be made in the metastatic
potential of cells and the question of cell dormancy. It remains to be hoped that
this aspect of minimal residual disease will be granted more attention in future.
PMID- 11006938
TI - [The normal bone marrow and its variations in MRT].
AB - Physiology and age-dependent changes of human bone marrow are described. The
resulting normal distribution patterns of active and inactive bone marrow
including the various contrasts on different MR sequences are discussed.
PMID- 11006939
TI - [Proton-MR spectroscopy of the spinal bone marrow. An analysis of physiological
signal behavior].
AB - BACKGROUND: Magnetic resonance imaging has shown to be a sensitive method for
diagnostics of the red bone marrow, the composition of which changes
physiologically and during pathological processes. However, the interpretation of
MRI in patients with disorders of the red bone marrow is very difficult. The aim
of this study was the characterization of the proton spectrum of healthy bone
marrow and its age- and sex-dependent changes to obtain a data basis for
measurements in patients. METHODS: 154 healthy volunteers have been examined.
After imaging, a spectroscopic measurement was performed to determine the
relative intensities of fat and water, and their respective T2 times. RESULTS:
While T2 (water: 46.9 ms and fat: 75.4 ms) does not depend on age or sex, the
relative signal intensity of fat increases by about 6% per decade. In the age
groups between 31 and 50 years it diverges significantly between men (43.5%) and
woman (32.5%) (p < or = 0.01, Mann-Whitney-Test. CONCLUSIONS: Proton spectroscopy
can increase the reliability of diagnosis by offering information on composition
of the marrow. The analysis of spectroscopic measurements requires exact
knowledge about normal physiological values.
PMID- 11006940
TI - [The MR characterization of the composition of the hematopoietic bone marrow. The
findings in generalized neoplasms and the monitoring of therapy].
AB - PURPOSE: Methodological work was performed in the field of magnetic resonance
imaging (MRI) and spectroscopy (MRS) in order to develop suitable tools for non
invasive characterization of hematopoietic bone marrow. The methods were applied
for the assessment of normal values in healthy persons and to examine patients
with generalized hematological diseases or to monitor effects of therapies
influencing the composition of bone marrow. METHODS: Besides standard techniques
of MRI as T1- or T2-weighted methods, chemical shift techniques for selective
visualization of water or lipid components were applied. The method of
magnetization transfer (MT) contrast was used with the intention to differentiate
between multiple water containing tissue compartments (intra- vs. extracellular
space). A further approach was the determination of the magnetic field
distribution within spongy bone marrow. Besides investigations in healthy
volunteers, prospective clinical studies were carried out in patients suffering
from acute leukemia during their initial treatment and in patients who underwent
high-dose therapy with following peripheral blood stem cell transplantation
(PBSCT). RESULTS: Especially MR techniques for selective imaging of water of fat
signals and proton spectroscopy yielded a high sensitivity to primarily
pathological or therapeutically induced changes of hematopoietic bone marrow.
Application of MT allowed an improved differentiation of the tissue compartments
under PBSCT, which might result in temporary edema. Storage of hemosiderin in
bone marrow after blood transfusions and simultaneous hematopoietic insufficiency
could be revealed by methods sensitive to magnetic field inhomogeneities.
CONCLUSIONS: Methods of MRI and MRS allow to non-invasively characterize
hematopoietic bone marrow in the course of hematological diseases and during
therapy. Marked changes in the composition of hematological bone marrow are
detectable for extensive marrow areas. The prognostic relevance of the findings
has to be evaluated in future follow-up studies.
PMID- 11006941
TI - [The diagnostic problems in magnetic resonance tomography of the bone marrow in
patients with malignomas under G-CSF therapy].
AB - AIM: To study the effect of G-CSF therapy directly by MRI and 1H MRS in the
lumbar and femoral bone marrow and differentiate between malignant bone marrow
infiltration (MBMI) and reconversion of red marrow. METHODS: Thirteen patients
could be examined twice, before and during G-CSF medication and another six only
during treatment. T1 weighted spin-echo and opposed-phase gradient-echo images as
well as the spectroscopic data (T2 values, water content) were analysed. RESULTS:
After G-CSF a pathologic bone marrow signal intensity was seen in 8/13 (lumbar)
and 11/13 (femoral) patients respectively. The majority of the signal alterations
were diffuse (6 and 8), the minority focal (2 and 3). If a patient was
successfully stimulated, a significant increase in water content occurred (21%
lumbar, 34% femoral). T2 values did not change significantly, nor did they
correlate with the stimulation success. CONCLUSIONS: MR tomography and
spectroscopy are suitable to detect lumbar and femoral bone marrow stimulation by
G-CSF quantitatively and qualitatively. The changes may simulate MBMI. The
adequate judgement of G-CSF treated bone marrow without pretherapeutic images is
not possible.
PMID- 11006942
TI - [The diagnosis of plasmocytoma with MRT].
AB - BACKGROUND: In multiple myeloma 5 different infiltration patterns can be
differentiated: 1. normal appearance of bone marrow, 2. focal involvement, 3.
homogeneous diffuse infiltration, 4. combined diffuse and focal infiltration, 5.
"salt- and pepper" pattern with inhomogeneous bone marrow with interposition of
fat islands. METHODS: For the fast and total acquisition of all patterns a
combination of a T1-weighted spin echo sequence and a fat suppression technique
is superior. The focal involvement is clearly demonstrated as areas of high
signal intensity on e.g. STIR images. Diffuse involvement can be quantified
objectively by calculation of the percentage of signal intensity increase after
contrast material injection. MRI is superior to X-ray in focal and diffuse
involvement. With ultrafast sequences a "screening" of the whole red bone marrow
as for myeloma infiltration is possible. PROGNOSIS: In prognosis studies diffuse
infiltration is inferior to focal involvement. Patients without bone marrow
infiltration have a significantly longer survival than patients with bone marrow
infiltration in MRI at the time of diagnosis. However, even patients in stage one
of disease (Durie and Salmon) and negative X-ray films can show bone marrow
infiltration in MRI. Those patients often show an early disease progression. Good
response to therapy in focal involvement are: reduction of signal intensity on T2
weighted spin echo images, lack or rim-like enhancement after contrast material
injection or even a normalisation of bone marrow signal. In case of diffuse
involvement a partly patchy reconversion to fatty marrow can be seen.
PMID- 11006943
TI - [Functional magnetic resonance tomography in the diagnosis and therapy monitoring
in multiple myeloma].
AB - AIM OF THE STUDY: Investigation of the quantitative microcirculation parameters
amplitude A and exchange rate constant k21 determined by contrast-enhanced
dynamic magnetic resonance imaging (d-MRI) in multiple myeloma (MM). METHODS: d
MRT of lumbar spine and right spina iliaca superior posterior of 16 controls
(ctr) and 35 patients with active MM. Generation of colour-coded images of
microcirculation parameters superimposed onto static MRI images. RESULTS:
Amplitude A and k21 parameters were significantly increased in patients with MM
and down modulated by therapy in 7 of 8 MM cases in a follow-up investigation [p
< 0.01; median Actr = 0.2 (0.09-0.4); median AMM = 0.93 (0.2-1.52); median k21ctr
= 0.09 min-1 (0.03-0.9); median k21MM = 4.57 min-1 (0.21-23.8)]. Thirteen
patients revealed a "diffuse" and 22 a "focal" pattern of distribution of
microcirculation parameters. Bone marrow biopsies in 8 cases revealed an
correlation between bone marrow plasma cell infiltration and increased
microcirculation parameters. CONCLUSION: Identification of microcirculation
changes by d-MRI is a novel imaging technique for the detection and monitoring of
MM bone lesions.
PMID- 11006945
TI - [Bone manifestations in non-Hodgkin's lymphoma in childhood and adolescence].
AB - PURPOSE: Skeletal manifestation of Non-Hodgkin's lymphoma is rare in pediatric
patients. Objective of the study was to determine imaging features, before and
after treatment, and to correlate these features with clinical outcome. METHODS:
A retrospective analysis of 1246 patients from two therapy studies (NHL-BMF-90
and 95) was performed. Imaging studies of 63 patients with bone involvement of
lymphoma were reevaluated. RESULTS: Incidence of initial bone involvement in Non
Hodgkin's lymphoma was 6.8%. Distribution was best assessed by bone scan, MRI
revealed larger areas of marrow involvement and detected additional lesions.
Sites of predilection were long bones of the lower extremities with epiphyseal
involvement in 39%. Residual signal alterations in MRI after successful therapy
remained in 71%. Osteonecrosis after therapy was a common finding. Clinical
outcome war not correlated to the presence of bone involvement. CONCLUSIONS:
Since clinical outcome is not effected by bone involvement in childhood NHL,
value of screening may be limited. Knowledge of imaging characteristics is
mandatory for initial evaluation of primary osseous lymphomas and symptomatic
lesions as well as for therapy controls.
PMID- 11006944
TI - [The value of diffusion-weighted MRT in assessing the bone marrow changes in
vertebral metastases].
AB - AIM OF THE STUDY: The aim of the study was the evaluation of the diffusion
coefficient (ADC) of vertebral metastasis and regular vertebral bodies with
diffusion weighted MRI (DWI). DWI evaluates the tissue-specific molecular
diffusion of protons. In tissues with high cell densities (neoplasm) a decreased
ADC can be expected due to restricted diffusion according to an exaggerated
amount of intra- and intercellular membranes (i.e. diffusion barriers). METHODS:
In 5 breast cancer patients the ADC of both known vertebral metastases and of
adjacent regular vertebral bodies were measured with DWI (1.0 T; Phased-Array
Body-Coil; b: 880 and 440 s/mm2). RESULTS: The ADC of regular vertebral bodies
(1.3 +/- 0.23 x 10(-3) s/mm2) was significantly (p < or = 0.0002) higher than in
vertebral metastases (0.39 +/- 0.11 x 10(-3) s/mm2). CONCLUSIONS: These data
demonstrate that the ADC can be reliably measured in vertebral bodies. The
quantitative evaluation of the ADC in vertebral bodies seems to be an objective
and comparable parameter for differentiating malign from benign vertebral tissue.
PMID- 11006946
TI - [Ischemia of the lower extremity due to a persistent a. ischiadica--a possible
interventional therapeutic approach].
AB - The sciatic artery is a rarely seen variant of the vessels of the lower limb.
Anatomically it is the prolongation of the inferior gluteal artery and
accompanies the sciatic nerve from the sciatic foramen to the knee. More than
other vessels, the sciatic artery shows vasculopathies like diffuse dilatation or
aneurysms. This report describes an interesting case of embolic acute ischemia,
caused by a persistent sciatic artery with an aneurysm. We treated the ischemia
with intra-a. lysis and bridged the aneurysm with an covered stent.
PMID- 11006947
TI - [Sellink is not "by" Sellink. A letter on the work of S. Feuerbach and J.
Scholmerich, Radiologe (2000) 40: 324-38].
PMID- 11006948
TI - [Intraspinal, epidural space-occupying lesion].
PMID- 11006949
TI - [Interventions in hemodialysis shunts].
PMID- 11006950
TI - NMDA blockade attenuates caspase-3 activation and DNA fragmentation after
neonatal hypoxia-ischemia.
AB - The aim was to study the effects of an NMDA receptor antagonist on caspase-3
activation and DNA fragmentation after hypoxia-ischemia (HI) in 7-day-old rats.
Animals were treated with vehicle or MK-801 (0.5 mg/kg) directly after HI and
sacrificed 8, 24 or 72h later. MK-801 reduced injury (by 53%), cells positive for
active caspase-3 (by 39%) and DNA fragmentation (by 79%) in the cerebral cortex.
Furthermore, MK-801 significantly decreased caspase-3 activity, and Western blots
revealed a tendency towards decreased proteolytic cleavage of the caspase-3
proform. The data imply that NMDA receptors are involved in the activation of
apoptotic processes in the immature brain after HI.
PMID- 11006951
TI - Growth regulation of astrocytes and C6 cells by TGFbeta1: correlation with gap
junctions.
AB - Transforming growth factor (TGF) beta1 enhanced in vitro [3H]thymidine
incorporation into C6 cells and reduced that of astrocytes in the presence of a
high serum concentration. It concomitantly raised the gap junction intercellular
communication (GJIC) in normal astrocytes but reduced the coupling of C6 cells,
and respectively increased or decreased the proportion of P2-phosphorylated
connexin (Cx) 43 isoform in these cells. Finally, octanol, which inhibited GJIC
in both cell types, increased the thymidine incorporation in C6 cells, but
neither altered the proliferation of astrocytes nor their response to TGFbeta1.
These data indicate that an inhibition of gap junction intercellular
communication, due to an altered phosphorylation of connexin 43, may contribute
to the proliferative response of C6 glioblastoma cells to TGFbeta1.
PMID- 11006952
TI - Visually induced activity in human frontal motor areas during simple visuomotor
performance.
AB - Visuomotor tasks elicit neuronal activity in primate motor areas at relatively
short latencies. Although this early activity embodies features of visual
responses (short latency, stimulus-dependency), its sensory nature has been
questioned. We investigated neural correlates of visuomotor performance in human
motor areas using scalp and intracranial event-related potential measures. A
simple visuomanual reaction-time task evoked early potentials at 133-145 ms post
stimulus which occurred much earlier than the motor potentials of the same
region. The amplitude of the early potentials covaried with stimulus location and
was independent of parameters of the motor response. Because of their timing,
stimulus-dependency and characteristics of our behavioral task, the early
potentials are suggested to reflect neuronal responses of sensory nature rather
than processing related to pure motor aspects of the task.
PMID- 11006953
TI - Effects of serotonergic 5-HT1A and 5-HT1B ligands on ventral pallidal neuronal
activity.
AB - To clarify the role of the 5-HT system in limbic outputs, the present study
compared the effects of the 5-HT1A agonist 8-OH-DPAT and the 5-HT1B agonist CP
94253 with the non-selective 5-HT agonist TFMPP on the firing rate of ventral
pallidal (VP) neurons recorded in chloral hydrate-anesthetized rats. 8-OH-DPAT
(0.25-256 microg/kg i.v.) dose-dependently enhanced (9/26 neurons) or suppressed
(8/26) activity, and the 5-HT1A antagonist (+)WAY-100135 often attenuated these
responses. TFMPP (0.011-1.453 mg/kg i.v.) dose-dependently reduced the firing
rate of 7/8 VP neurons tested. In contrast, CP-94253 (0.013-12.8 mg/kg i.v.) had
little or no effect. In sum, these data suggest that the 5-HT1A receptor appears
to be particularly important in influencing limbic outputs mediated via the VP.
PMID- 11006954
TI - Expression of intercellular adhesion molecule-1 in C6 glioma cells is up
regulated by thyroid hormone.
AB - ICAM-1 is a cell surface adhesion glycoprotein playing an essential role in
inflammatory responses. We have investigated the effects of the thyroid hormone
T3 on the expression of the ICAM-1 gene in C6 glioma cells. In these cells, T3
stimulated the ICAM-1 protein expression significantly after 24 h of treatment.
The induction of ICAM-1 by cytokines such as interleukin 1beta or tumour necrosis
factor TNF as well as by lipopolysaccharide or T3 can be suppressed by the two
anti-inflammatory compounds dexamethasone and parthenolide. The C6 glioma cell
line could then be a useful model for studying the effect of T3 hormone on the
expression of specific genes in glial cells, especially genes involved in
lymphocyte-glial cell interactions.
PMID- 11006955
TI - PET shows that odors are processed both ipsilaterally and contralaterally to the
stimulated nostril.
AB - The olfactory nerve is the only cranial nerve with established ipsilateral
primary cerebral anatomical projections. Whether these projections correspond to
the functional pathways for monorhinal processing of odor perception is, however,
unknown. We therefore studied cerebral blood flow (rCBF) with [15O]butanol-PET in
18 healthy females during monorhinal smelling of single odors (OS) and odorless
air (AS). Compared with AS, OS activated right amygdala and piriform cortex
(confluent cluster), right orbitofrontal cortex, left insula, right thalamus, and
anterior cingulate. A post hoc analysis showed that the first three regions were
activated independently of the stimulated side, but that right orbitofrontal rCBF
was higher during the right nostril stimulations. Left insula was activated
mainly by the right nostril stimuli, and right thalamus by the left nostril
stimuli. Odors seem to be processed both ipsi and contralaterally, with a right
hemisphere preponderance irrespective of the stimulated nostril.
PMID- 11006956
TI - A study of the apparent diffusion coefficient of grey and white matter in human
ischaemic stroke.
AB - We examined whether there was any difference in the value, and temporal
evolution, of the apparent diffusion tensor trace (ADC) in acute and subacute
grey and white matter lesions. Thirty-seven patients underwent diffusion imaging
once (up to 3 days), 15 patients were scanned twice (up to 7 days), and seven
patients were scanned three times (up to 14 days) after stroke. Values of the
ratio of ischaemic to contralateral ADC (ADCr) were reduced on average by 30%
(p<0.001) in the whole hyperintense region up to 7 days post-ictus. No difference
was seen between ADCr values of grey and white matter in individual subjects
within the patient groups scanned up to 7 days. However, in the subgroup of
patients scanned beyond 7 days, ADCr for grey matter rose significantly (p=0.02)
from ADCr approximately 0.7 (< 7 days) to 0.95 (> or = 10 days). This increase
did not occur in white matter whose ADCr remained fairly constant (ADCr
approximately 0.7) over the time course of the study.
PMID- 11006957
TI - Causal influences in primate cerebral cortex during visual pattern
discrimination.
AB - Anatomical studies of the visual cortex demonstrate the existence of feedforward,
feedback and lateral pathways among multiple cortical areas. Yet relatively
little evidence has previously been available to show the causal influences of
these areas on one another during visual information processing. We
simultaneously recorded event-related local field potentials (LFPs) from surface
to-depth bipolar electrodes at six sites in the ventral region of the right
hemisphere visual cortex in a highly trained macaque monkey during performance of
a visual pattern discrimination task. Applying a new statistical measure, the
short-time directed transfer function (STDTF), to the LFP data set, we charted
the changing strength and direction of causal influence between these cortical
sites on a fraction-of-a-second time scale. We present results showing, for the
first time, the dynamics of distinct feedforward, feedback and lateral influences
in the ventral portion of the primate visual cortex during visual pattern
processing.
PMID- 11006958
TI - Global and local processing of visual patterns in macaque monkeys.
AB - Human subjects generally perceive the global form of hierarchically organized
visual patterns faster than the local form. To test whether macaque monkeys show
a similar precedence for global processing, two monkeys were trained to
discriminate either the global or local form of hierarchical visual patterns. The
response time to discriminate the global form was shorter than that to
discriminate the local form. Consistent patterns, in which the global and local
forms were identical, were discriminated faster than inconsistent ones, in which
the two forms were different from each other, both in discrimination of the
global form and of the local form. Similar results were obtained in two human
subjects who were subjected to the identical tests. The results suggest that,
both in monkeys and humans, the global form is processed faster than the local
form with a temporal overlap which allows bidirectional interactions between the
two processes.
PMID- 11006960
TI - Simultaneous bilateral mismatch response to right- but not leftward sound
lateralization.
AB - Magnetoencephalography (MEG) was used to compare mismatch responses between
hemispheres to changes in sound-source direction. Sixteen adults listened
passively to two types of complex non-language sounds presented in separate
blocks with midline standards and right- and left-lateralized deviants. Mismatch
dipole amplitudes were larger contra- than ipsilaterally to the deviants. Both
hemispheres processed right deviants simultaneously, whereas to left deviants,
the left dipole peaked 20 ms later than the right dipole. A second experiment
using the same standards but midline spectral deviants showed no interhemispheric
differences. Here mismatch latencies were about 60 ms longer than in the location
mismatch experiment. This suggested both fast, contralaterally dominant location
mismatch responses and facilitated detection of auditory spatial deviance in the
right hemifield.
PMID- 11006959
TI - Involvement of the sigma1 receptor in the cocaine-induced conditioned place
preference.
AB - The sigma1 (sigma1) receptor constitutes a particular target of cocaine believed
to be involved in some of its behavioral effects. In the present study, its
involvement in the rewarding effect of cocaine was examined using the conditioned
place preference (CPP) procedure. CPP was induced in C57Bl/6 mice injected
repeatedly with cocaine (20 mg/kg, i.p.). The selective sigma1 receptor
antagonists NE-100 and BD1047 (1-10 mg/kg, i.p.) significantly attenuated or
blocked the cocaine-induced CPP. Animals treated centrally with a sigma1 receptor
antisense oligodeoxynucleotide failed to develop cocaine-induced CPP, unlike
mismatch controls. The sigma1 receptor thus appears to be critically involved in
the development of the cocaine-induced CPP and, in consequence, may constitute a
promising approach to blocking cocaine reward.
PMID- 11006961
TI - Auditory cortex evoked magnetic fields and lateralization of speech processing.
AB - Potential use of different auditory evoked brain responses for determining
cerebral lateralization of speech function was evaluated. Cortical magnetic
fields elicited by plosive syllables or complex non-speech sounds analogous to
them were recorded with 122-channel magnetometer. We estimated parameters of
magnetic P1, N1 and P2 responses to both stimuli in the two hemispheres and found
no hemispheric asymmetry for any of the responses. No correlation between the
right-ear advantage, determined with dichotic listening test, and any of
asymmetry indexes, calculated for the speech-elicited responses, was observed.
These results suggest that P1, N1 and P2 responses to speech signals do not
indicate lateralization of speech function in the brain. The results are
discussed in relation to previous studies suggesting that the mismatch negativity
(MMN) seems to be the only early auditory cortex response sensitive to the
lateralization of speech function.
PMID- 11006962
TI - Mossy fiber sprouting is dissociated from kindling of generalized seizures in the
guinea-pig.
AB - Controversy surrounds whether aberrant mossy fiber sprouting in the hippocampus
is necessary for the establishment of seizure states. We investigated the
association between mossy fiber sprouting and kindling in guinea-pigs, using
either single-site or alternate-site stimulation. Kindling with single-site
amygdaloid stimulation did not induce significant sprouting, despite the
development of partial seizures. In contrast, single-site septal and alternating
amygdaloid-septal stimulation produced moderate but significant sprouting in
about 60% of animals that failed to develop stage 5 generalized seizures. Since
the magnitude of sprouting was similar despite striking differences in the
intensity of seizures that developed, we conclude that mossy sprouting is not
causally associated with seizure development.
PMID- 11006963
TI - Rapidly turned over protein maintains metabotropic synaptic transmission in
Purkinje cells.
AB - It has generally been thought that protein synthesis is required for relatively
slow cellular processes such as synaptogenesis and synaptic plasticity. In this
study on rat cerebellar slices, we found that metabotropic glutamate receptor
mediated synaptic transmission to cerebellar Purkinje cells was quickly and
persistently depressed by brief (5 min) applications of translational inhibitors,
which were confirmed to induce quick and persistent depression of protein
synthesis in cerebellar tissues. Brief applications of transcriptional inhibitors
also depressed metabotropic synaptic transmission, but progressively over 1 h,
presumably due to depletion of mRNAs in the dendrites. Results of this study
indicate the presence of a unique protein(s) that is dynamically involved in
metabotropic synaptic transmission.
PMID- 11006964
TI - Language functional neuro-imaging changes following focal left thalamic
infarction.
AB - The involvement of the left thalamus in language function has been largely
demonstrated through the effects of thalamic lesion and/or stimulation upon
language. However, the pathophysiological mechanisms underlying thalamic aphasias
remain a matter of debate. We report here on changes in the pattern of brain
activity in auditory word processing, verb generation and visual lexical decision
in a patient who sustained left thalamic infarct following the surgery of
intractable mesio-temporal epilepsy with left hippocampal sclerosis. To some
extent, our findings exemplify the way the left thalamus brings on line the
cortical networks involved in language processing, suggested in the term
'selective engagement'.
PMID- 11006965
TI - Cytoplasmic residues influence the voltage-dependence of the gating of human K+
channels.
AB - Shaker type potassium channels are strongly voltage dependent and potassium
selective. Kv1.4 channels from a variety of sources exhibit a much shallower
voltage-dependence of activation than other members of the family. We have made a
chimeric construct consisting of the N-terminal chain of hKv1.1 spliced onto the
transmembrane portion of hKv1.4 (IN/4). When expressed in Xenopus oocytes, the
chimeric channel exhibits a voltage dependence that is similar to hKv1.1 although
the voltage sensing and transduction machinery presumably reside in the
transmembrane portion of the channel. Loss of the N-terminal ball and chain from
hKv1.4 is not responsible for this as a truncation construct, starting close to
the splice junction, has the same voltage-dependence as full length hKv1.4. We
suggest that residues from the N-terminal chain of hKv1.1 interact with the
machinery that transduces movement of the voltage sensor into channel opening. If
so, this chimeric construct could provide a handle to the identification of
elements of this transduction machinery.
PMID- 11006966
TI - A systematic representation of interaural intensity differences in the auditory
cortex of the pallid bat.
AB - The current model of cortical processing of auditory spatial information is based
on an orthogonal representation of frequency and binaural response properties,
but how this arrangement leads to representation of space in the auditory cortex
is unclear. This study describes the first evidence of a cortical substrate for
the systematic representation of space in a region of primary auditory cortex of
the pallid bat that subserves passive sound localization. The organizational
feature of this region is a systematic shift in sensitivity to interaural
intensity differences across the cortical surface, suggesting a topographic
representation of horizontal space based on the distribution of activity within
the neuron population.
PMID- 11006967
TI - Chronic repetitive transcranial magnetic stimulation induces subsensitivity of
presynaptic serotonergic autoreceptor activity in rat brain.
AB - Repetitive transcranial magnetic stimulation (rTMS) is a novel procedure which
has proven effective in the treatment of major depression. We administered rTMS
chronically to rats in order to determine whether this procedure affected
serotonergic neurotransmission in the prefrontal cortex. Basal 5-HT levels, and
the effects of challenges with the 5-HT1A receptor agonist 8-OH-DPAT and the 5
HT1B antagonist GR 127935 on 5-HT levels were determined using in vivo
microdialysis. Rats which had undergone chronic rTMS showed reduced responses to
both challenges, indicating subsensitivity of both the presynaptic 5-HT1A
autoreceptors situated somatodendritically in the raphe nuclei and the 5-HT1B
autoreceptors situated on nerve terminals. Since such subsensitivity has been
demonstrated after other antidepressant treatments, our results indicate that
these treatments and rTMS may have a common mechanism of action.
PMID- 11006968
TI - Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of
autism.
AB - In this study we report a convergence of behavioural and neuroanatomical evidence
in support of an amygdala hypothesis of autism. We find that people with high
functioning autism (HFA) show neuropsychological profiles characteristic of the
effects of amygdala damage, in particular selective impairment in the recognition
of facial expressions of fear, perception of eye-gaze direction, and recognition
memory for faces. Using quantitative magnetic resonance (MR) image analysis
techniques, we find that the same individuals also show abnormalities of medial
temporal lobe (MTL) brain structure, notably bilaterally enlarged amygdala
volumes. These results combine to suggest that developmental malformation of the
amygdala may underlie the social-cognitive impairments characteristic of HFA.
This malformation may reflect incomplete neuronal pruning in early development.
PMID- 11006969
TI - Ca2+-dependent desensitization of AMPA receptors.
AB - The effect of changes in the external concentrations (0.4-10 mM) of Ca2+ ions on
AMPA receptors (AMPARs) of different subunit composition was studied on freshly
isolated rat brain neurones. Ca2+ produces rapid and reversible voltage
independent inhibition of AMPARs. Ca2+-permeable and Ca2+-impermeable AMPARs are
equally sensitive to external Ca2+ suggesting that the effect is not addressed to
the ion channel. The inhibition of responses evoked by AMPA is significantly
larger than those evoked by kainate or glutamate. Cyclothiazide and aniracetam,
which are known to prevent AMPAR desensitization, both greatly diminish
inhibition of AMPARs by Ca2+. Cyclothiazide is more potent than aniracetam in
both preventing of AMPAR desensitization and protecting against the Ca2+
inhibitory effect on hippocampal pyramidal cells. On giant cholinergic
interneurones of striatum, aniracetam but not cyclothiazide significantly
prevents inhibition by Ca2+. This agrees with available data on relative
abundance of flip and flop splice variants in these cell types. The results
suggest that Ca2+ may allosterically increase AMPA receptor desensitization
independently on subunit composition and splice variants.
PMID- 11006971
TI - Two distinct components of initial glutamate release synchronized with anoxic
depolarization in rat global brain ischemia.
AB - Numerous reports have suggested that anoxic depolarization is a critical event in
the pathogenesis of cerebral ischemia. Extracellular glutamate concentration
([Glu]e) is closely related to the pathogenesis of ischemia. Therefore, these
pathogenic mechanisms merit study, especially the relationship between [Glu]e
elevation and the ionic basis of early changes in membrane potential after
ischemic insult in vivo. It is often presumed from electrophysiological studies
that a causal relationship exists between impaired glutamate uptake and/or
progressive glutamate increase and anoxic depolarization, but few in vivo reports
have found any sign of a progressive increase of [Glu]e elevation preceding
anoxic depolarization. Recently, we reported the application of an oxygen
independent real-time technique for monitoring glutamate levels in the
extracellular space during in vivo ischemia, and demonstrated that the massive
glutamate release during ischemia is biphasic. In the present study, using this
real-time monitoring system, we carried out a more detailed analysis of the
initial events in the first phase of glutamate release during ischemia-induced
anoxic depolarization. The shape of the rising slope that forms the peak of the
first phase suggested two components. The second component was approximately 10
times steeper than the first, with two different components of the rise on the
way to the peak of the biphasic [Glu]e elevation. This is the first report to
demonstrate these components of the initial glutamate peak, and suggests a
progressive second component of the [Glu]e increase preceding Ca2+-dependent
release from synaptic vesicles with anoxic depolarization, in vivo.
PMID- 11006970
TI - nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but
not hyperthermia in mice.
AB - Methamphetamine (METH)-induced dopaminergic neurotoxicity is associated with
hyperthermia. We investigated the effect of several neuronal nitric oxide
synthase (nNOS) inhibitors on METH-induced hyperthermia and striatal dopaminergic
neurotoxicity. Administration of METH (5 mg/kg; q. 3 h x 3) to Swiss Webster mice
produced marked hyperthermia and 50-60% depletion of striatal dopaminergic
markers 72 h after METH administration. Pretreatment with the nNOS inhibitors S
methylthiocitrulline (SMTC; 10 mg/kg) or 3-bromo-7-nitroindazole (3-Br-7-NI; 20
mg/kg) before each METH injection did not affect the persistent hyperthermia
produced by METH, but afforded protection against the depletion of dopaminergic
markers. A low dose (25 mg/kg) of the nNOS inhibitor 7-nitroindazole (7-NI) did
not affect METH-induced hyperthermia, but a high dose (50 mg/kg) produced
significant hypothermia. These findings indicate that low dose of selective nNOS
inhibitors protect against METH-induced neurotoxicity with no effect on body
temperature and support the hypothesis that nitric oxide (NO) and peroxynitrite
have a major role in METH-induced dopaminergic neurotoxicity.
PMID- 11006972
TI - A moderate but not total decrease of mitochondrial membrane potential triggers
apoptosis in neuron-like cells.
AB - The effects of various degrees of perturbation of the mitochondrial membrane
potential (mt delta psi) on apoptosis was investigated by intensified
fluorescence digital-imaging microscopy on neuron-like cells, ND7. Mt delta psi
was either decreased by 40% by the protonophore carbonyl cyanide p
trifluoromethoxyphenylhydrazone (FCCP 100 nM, 15 min) or completely collapsed
(FCCP 10 microM, 60 min). A moderate decrease of mt delta psi induced a reduction
of mitochondrial NADH, followed by exposure of phosphatidyl serine and then by
chromatin condensation, 36% of nuclei being condensed 60 min after FCCP
treatment. During these stages, mitochondrion morphology was fully preserved. In
contrast, no chromatin condensation was observed after a rapid and total
dissipation of mt delta psi. These results suggest that a partial decrease of mt
delta psi would allow mitochondrial functions required to trigger apoptosis to be
sustained.
PMID- 11006973
TI - In vivo imaging of activated microglia using [11C]PK11195 and positron emission
tomography in patients after ischemic stroke.
AB - Neuroprotective strategies are currently being developed for stroke patients.
Although the focus is on the development of early treatment the importance of
late pathogenetic events is increasingly recognized. To investigate the
microglial reaction in stroke we used a marker for activated microglia,
[11C]PK11195, and PET in five patients with ischemic stroke 5-53 days after
infarction. In one patient serial measurements were made. We demonstrated in each
individual and at each point in time that a microglial reaction takes place in
the area where T1 weighted MRI (magnetic resonance imaging) shows intensity
changes. We consider this PET method as a promising tool to study the late
pathogenetic consequences of cerebral infarction and to evaluate neuroprotective
strategies with respect to the consequences of the microglial activation.
PMID- 11006974
TI - Ischemic tolerance preserves propagation of membrane depolarization.
AB - The functional integrity of the synaptic connections within the hippocampus in
gerbils that had acquired ischemic tolerance was investigated. The propagation of
membrane depolarization across the hippocampus in response to electrical
stimulation of CA1 was monitored with the use of a high speed optical recording
technique. In comparison to control slices, propagation was significantly
depressed and depolarization was shortened in slices from gerbils subjected to 5
min of ischemia. Hippocampal slices from gerbils who were preconditioned with
prior sublethal ischemia demonstrated only a slight reduction in propagation. The
duration of depolarization was longer than that of ischemia group. These findings
suggest that ischemia induces a functional disturbance of synaptic transmission
and membrane depolarization. Ischemic preconditioning significantly reduced the
extent of this functional disturbance.
PMID- 11006975
TI - Immunohistochemical study of nucleoporin p62 in the hippocampus and hypothalamus
of the rat brain.
AB - We immunohistochemically studied the distribution of nucleoporin p62 in the
hippocampus and hypothalamus of rat brain. Previous reports have shown the
presence of p62-immunoreactivity (ir) in the nuclear rim in the non-neuronal
cells, but the present study showed that of p62-ir within the nucleus in addition
to the nuclear rim in the neuronal cells of the hippocampus and hypothalamic
nuclei; in these areas the glucocorticoid receptor (GR) undergoes
nucleocytoplasmic translocation determined by ligand. We analyzed the expression
of p62-ir after adrenalectomy (ADX). ADX changed the localization of GR-ir from
the nucleus to the cytoplasm, but did not change the localization or
immunoreactivity of p62, suggesting that nucleoporin p62 is stable regardless of
intracellular signal transduction between the cytoplasm and the nucleus.
PMID- 11006976
TI - A cortical region sensitive to auditory spectral motion.
AB - The functional architecture of human auditory cortex is still poorly understood
compared with that of visual cortex, yet anatomical and electrophysiological
studies in non-human primates suggest that the auditory cortex also might be
functionally specialized, in a model of parallel and hierarchical organization.
In particular, spectral changes such as the formant transitions of speech, or
spectral motion (SM) by analogy with visual motion, could be processed in
specialized cortical regions. In this study, positron emission tomography (PET)
was used to identify which auditory cortical region are involved in SM analysis.
We found that a bilateral secondary auditory cortical region, located in the
caudal-lateral belt of auditory cortex, was more sensitive to auditory stimuli
containing spectral changes than to matched stimuli with a stationary spectral
profile. This result suggests that analogies between sensory systems could prove
useful in the research into the functional organization of the auditory cortex.
PMID- 11006977
TI - p53 and Bax implication in NMDA induced-apoptosis in mouse hippocampus.
AB - Seven days after in vivo intrahippocampal administration of NMDA, 3'-OH DNA
fragmentations and Bax protein expression were detected in hippocampal neurons of
p53+/+ but not p53-/- transgenic mice. Interestingly, neurons showing pycnosis,
an early apoptotic phenomena, were present in all genotypes. These results
confirm that apoptotic 3'OH DNA fragmentations and Bax protein induction during
NMDA-induced apoptosis in adult hippocampal neurons are p53 dependent.
PMID- 11006978
TI - Activity patterns of human somatosensory cortex adapt dynamically to stimulus
properties.
AB - Long-term synchronous tactile stimulation of two sites of the body results in
integrated, overlapping cortical representations whereas asynchronous stimulation
leads to segregated representations. To investigate the cortical capacity to
adapt dynamically to stimulation properties 22 subjects were stimulated at digits
1, 3 and 5 of both hands in either random or fixed order. Changes in the
functional organization of the somatosensory cortex were inferred by
neuromagnetic source analysis based on somatosensory evoked magnetic fields.
Compared to the stimulation in random sequence, the stimulation in fixed order
revealed a reduction in distance between the cortical representation of D1 and
D3. We conclude that the pattern of activation in the somatosensory cortex adapts
dynamically to the spatio-temporal characteristics of the stimuli.
PMID- 11006979
TI - Fish inner ear otoliths stop calcium incorporation after vestibular nerve
transection.
AB - Previous investigations revealed that the growth of fish inner ear otoliths
(otolith size and calcium incorporation) depends on the amplitude and the
direction of gravity, suggesting the existence of a (negative) feedback
mechanism. In a search for the regulating unit, the vestibular nerve was
unilaterally transected in neonatal swordtail fish (Xiphophorus helleri) which
were subsequently incubated in the calcium-tracer alizarin-complexone. Calcium
incorporation and thus otolith growth ceased on the operated head sides,
indicating that the brain is significantly involved in regulating otolith growth.
PMID- 11006981
TI - Role of nitric oxide in rat locus coeruleus in hypoxia-induced hyperventilation
and hypothermia.
AB - The locus coeruleus modulates the ventilatory and thermoregulatory response to
hypoxia and contains nitric oxide synthase. Therefore, we examined the effects of
L-NAME unilaterally microinjected into the locus coeruleus on hypoxic
hyperventilation and hypothermia. Ventilation and body temperature were measured
before and after microinjection of L-NAME (100 nmol/0.5 microl) into the locus
coeruleus, followed by hypoxia. Control rats received microinjection of D-NAME
(an inactive enantiomer of L-NAME). Under normoxia, L-NAME treatment did not
affect ventilation or body temperature. D-NAME did not affect hypoxia-induced
hyperventilation and hypothermia. L-NAME treatment reduced the ventilatory
response to hypoxia but did not affect hypoxia-induced hypothermia. These data
suggest that nitric oxide in the locus coeruleus is involved in the ventilatory
response to hypoxia, exercising an inhibitory modulation on the locus coeruleus
neurons, but plays no role in hypoxia-induced hypothermia.
PMID- 11006980
TI - The representation of articulation in the primary sensorimotor cortex.
AB - Bilabial, alveolar and velar sounds are produced at different locations around
the oral cavity. fMRI was used to localize cortical representation of
articulation in seven healthy subjects during repetitive lip and vertical tongue
movements as well as repetitive articulation of /pa/ (bilabial), /ta/ (alveolar),
/ka/ (velar consonants) and a combination of all three in /pataka/. Centers of
gravity (COG) analysis of fMRI activation in the primary motor (M1) and sensory
cortex (S1) revealed /pa/- adjacent to lip representation and /ta/- articulation
to tongue representation. The articulation of /pataka/ showed an activation
pattern with a combination of the two M1/S1-components and additional activation
in the supplementary motor area.
PMID- 11006982
TI - Remote discharges in the posterior language area during basal temporal
stimulation.
AB - A 23-year-old woman with refractory complex partial seizures underwent
implantation of subdural grid electrodes over the left hemisphere to map
epileptic foci and language function. Aphasic symptoms occurred during
stimulation of the basal temporal area, which were always associated with
intrastimulus remote discharges (ISRDs) in the classical posterior language area.
No sequential language deficits occurred after anterior temporal lobectomy
including the basal temporal area. These results suggest a close functional
relationship between the basal temporal area and posterior language area in
patients with temporal lobe epilepsy. ISRDs may explain the paradoxical
observation that resection of the basal temporal language area results in no
language deficits.
PMID- 11006983
TI - Spinal cord injury in rat: treatment with bone marrow stromal cell
transplantation.
AB - We tested the hypothesis that transplantation of bone marrow stromal cells (MSCs)
into the spinal cord after a contusion injury promotes functional outcome. Rats
(n = 31) were subjected to a weight driven implant injury. MSCs or phosphate
buffered saline was injected into the spinal cord 1 week after injury. Sections
of tissue were analyzed by double-labeled immunohistochemistry for MSC
identification. Functional outcome measurements using the Basso-Beattie-Bresnehan
score were performed weekly to 5 weeks post-injury. The data indicate significant
improvement in functional outcome in animals treated with MSC transplantation
compared to control animals. Scattered cells derived from MSCs expressed neural
protein markers. These data suggest that transplantation of MSCs may have a
therapeutic role after spinal cord injury.
PMID- 11006984
TI - Neurite outgrowth in developing mouse spinal cord neurons is modulated by glycine
receptors.
AB - The effect of glycine receptor activation on neurite outgrowth and survival was
studied in 5 DIV (days in vitro) spinal neurons. These neurons were depolarized
by spontaneous synaptic activity and by glycine, but not by glutamate. These
responses were accompanied by increases in intracellular calcium concentration
measured with Indo-1 and Fluo-3. Glycine (100 microM, 48 h) increased (46 +/- 6%)
the number of primary neurites and total neuritic length. This effect was
mediated by synaptic activity and calcium influx because TTX (1 microM) and
nimodipine (4 microM) blocked the stimulatory effect of glycine. Neuronal
survival, on the other hand, was not affected. This study shows for the first
time the modulatory effect of glycine receptors on spinal neuron development.
PMID- 11006985
TI - The neural correlates of orienting: an integration of fMRI and skin conductance
orienting.
AB - In fMRI studies, the averaging of neural activity across multiple trials might
obscure important psychophysiological subprocesses. The orienting response (OR)
is a distinctive subprocess signalling the active orientation of attention
towards potentially significant events. We sought to elucidate fMRI activity
associated with visual stimuli that did or did not evoke simultaneously recorded
electrodermal ORs (using customised skin conductance recording). 'With-OR'
stimuli were associated with significant activity in the hippocampus, anterior
cingulate and ventromedial prefrontal cortex. Averaged analysis revealed activity
only in the expected visual circuits. Our results suggest that potentially
significant stimuli (with-OR) activate different functional networks to familiar
(without-OR) stimuli, and that orienting may therefore be an informative
subprocess to consider in cognitive fMRI studies.
PMID- 11006986
TI - PTX-sensitive and -insensitive synaptic modulation at the frog neuromuscular
junction.
AB - Pharmacological manipulations were used to examine the role of G proteins in
modulating synaptic transmission at the frog neuromuscular junction. Pertussis
toxin (PTX, a G protein antagonist) increased end-plate potential (epp) amplitude
but had no effect on the amplitude or frequency of miniature end-plate
potentials. Mastoparan (a G protein agonist) decreased epp amplitude, while
suramin (an antagonist) increased epp amplitude. The results suggest that PTX
sensitive G proteins tonically modulate synaptic transmission by reducing the
amount of transmitter released in response to presynaptic action potentials. We
also showed that endogenous ATP decreased transmitter release via P2 receptor in
a PTX-insensitive manner. Thus, at least two distinct mechanisms regulate
neuromuscular transmission; one is coupled to PTX-sensitive G proteins and the
other is not.
PMID- 11006987
TI - Two mirror-image sensory maps with domain organization in the mouse main
olfactory bulb.
AB - The glomerular sheet in the olfactory bulb (OB) provides an olfactory sensory map
identifying which odorant receptors (ORs) in the nose are activated by inhaled
odorants. How are the glomeruli spatially arranged in the OB? Using OCAM and
neuropilin-1 (NP1) as molecular markers for target glomeruli of distinct subsets
of olfactory axons, we demonstrate here that glomeruli are parceled into
topographically distinct domains. Spatial arrangement of these domains suggests
that each OB contains two mirror-image maps of the glomeruli. In situ
hybridization shows that the glomeruli representing the same OR are symmetrically
arranged; one in a domain in the lateral hemisphere and the other in a
corresponding domain in the medial hemisphere of the OB. These results suggest
that OB contains two symmetrical OR maps with similar domain organization.
PMID- 11006988
TI - Conduction velocity of the human spinothalamic tract as assessed by laser evoked
potentials.
AB - To study the conduction velocity of the spinothalamic tract (STT) we delivered
CO2 laser pulses, evoking pinprick sensations, to the skin overlying the
vertebral spinous processes at different spinal levels from C5 to T10 and
recorded evoked potentials (LEPs) in 15 healthy human subjects. These stimuli
yielded large-amplitude vertex potentials consisting of a negative wave at a peak
latency of about 200 ms followed by a positive wave at a peak latency of about
300 ms. The mean conduction velocity of the STT was 21 m/s, i.e. higher than the
reported velocity of the corresponding primary sensory neurons (type II AMH).
Because dorsal stimulation readily yields reproducible brain LEPs, we expect this
technique to be useful as a diagnostic tool for assessing the level of spinal
cord lesions.
PMID- 11006989
TI - Age-related decline in the functional response of striatal group I mGlu
receptors.
AB - In order to verify whether striatal group I metabotropic glutamate (mGlu)
receptors undergo functional alteration in ageing, the effects induced by the
selective agonist 3,5-dihydroxyphenylglycine (DHPG) in the striatum of young (3
months) and aged (24-25 months old) rats were compared. The ability of DHPG to
stimulate phosphoinositide (PI) hydrolysis (striatal slices), to influence
striatal dopamine release (in vivo microdialysis) and to potentiate the effects
of NMDA on extracellular field potential amplitude (extracellular recordings on
striatal slices) was reduced in the striatum of old vs young rats. These results
show an age-dependent reduction in the functional response of striatal group I
mGlu receptors, which may be one of the factors underlying the reduced ability
aged striatum to integrate information.
PMID- 11006990
TI - Frontal lobe damage and thalamic volume changes.
AB - The aim of this study was to investigate whether frontal lobe damage affects
thalamic volume in humans. Ipsilateral and contralateral thalamic areas were
measured in 0.5T T1-weighted sagittal magnetic resonance images in 12 patients,
first at the time of their surgery for relief of a unilateral frontal lobe brain
tumor and at follow-up approximately 2 years later. A 5% decrease in ipsilateral
and 4.5% increase in contralateral thalamic area was found over time (F(1,11) =
6.15, p < 0.05). We conclude that unilateral frontal lobe damage results in a
decrease in the ipsilateral thalamus and an increase in the contralateral
thalamus in humans in vivo. The findings may have implications for the
interpretation of the reported changes in thalamic volume in neuropsychiatric
diseases.
PMID- 11006991
TI - Inhibition of return and oculomotor control in the blind.
AB - Our attentional systems orient reflexively to novel environmental stimuli. Such
attentive orienting is typically followed by a prolonged period of inhibition,
known as inhibition of return (IOR), thought to be linked to the eye movement
system. It is widely believed that IOR may provide a tagging mechanism that
prevents perseveration, and thus facilitates attentional search. Using a tactile
variant of the peripheral spatial cuing paradigm, we show IOR in congenitally
blind adults and in an individual who had no eyes. These results demonstrate for
the first time that spatial IOR can occur in the absence of oculomotor control.
PMID- 11006992
TI - Is there a distortion of body projection in extracorporeal space in neglect
patients?
AB - Neglect patients often present with a rightward shift of the direction straight
ahead of body midline. We investigated whether directions ahead of other body
parts were similarly shifted or were differentially affected. Right brain-damaged
patients, with and without neglect, and normal subjects had to indicate by manual
pointings, the directions straight-ahead of the navel, the nose, the left and
right shoulders. In neglect patients, constant errors varied across directions
with a decrease in magnitude from left to right, suggesting a compression of body
projection in extracorporeal space. Moreover, the projection of the left hemibody
was smaller than the right in all subjects, with and without neglect. This
unexpected finding is discussed with regard to other spatial asymmetries observed
in normal subjects.
PMID- 11006993
TI - A case of musical agraphia.
AB - Damage to the left upper parietal lobule causes pure agraphia. However, we
experienced a patient who exhibited musical agraphia following such a lesion
after the agraphia improved. The patient was a 53-year-old female piano teacher.
After surgery, she exhibited agraphia and musical agraphia. There was no
expressive amusia, receptive amusia, aphasia, agnosia or apraxia. Fifteen months
post-surgery, when her agraphia had resolved, her abilities to read, write, and
copy music were evaluated. She could read and write single notes and musical
signs, but her ability to write a melody was seriously impaired. Furthermore, the
salient impairment was in writing rhythm rather than pitch. She could copy music,
but only slowly. We consider her a case of pure musical agraphia.
PMID- 11006994
TI - What is extinguished in auditory extinction?
AB - Extinction is a frequent sequel of brain damage, whereupon patients disregard
(extinguish) a contralesional stimulus, and report only the more ipsilesional
stimulus, of a pair of stimuli presented simultaneously. We investigated the
possibility of a dissociation between the detection and the identification of
extinguished phonemes. Fourteen right hemisphere damaged patients with severe
auditory extinction were examined using a paradigm that separated the
localization of stimuli and the identification of their phonetic content.
Patients reported the identity of left-sided phonemes, while extinguishing them
at the same time, in the traditional sense of the term. This dissociation
suggests that auditory extinction is more about acknowledging the existence of a
stimulus in the contralesional hemispace than about the actual processing of the
stimulus.
PMID- 11006995
TI - The antifungal activity of natamycin toward molds isolated from commercially
manufactured poultry feed.
AB - The antifungal activity of natamycin, a polyene antifungal compound, was
evaluated on molds isolated from commercial poultry feed. The antifungal activity
was measured by determination of the minimal inhibitory concentration (MIC) for
natamycin on molds growing on semisolid microbiological medium (potato dextrose
agar) containing pure natamycin at concentrations ranging from 0 to 200 mg/liter.
Natamycin exhibited a high degree of antifungal activity against the 191 isolates
of aspergilli used in this study, with average MIC values ranging from 5.08 to
40.1 mg/liter for Aspergillus fumigatus and Aspergillus parasiticus,
respectively. Natamycin was also equally effective in inhibiting the growth of
nonaflatoxigenic compared with aflatoxigenic isolates of Aspergillus flavus and
A. parasiticus. Natamycin was also efficacious against molds other than
aspergilli, with MIC values ranging from 2.15 to 5.80 mg/liter for Paecilomyces
and Rhizopus spp., respectively. Natamycin exhibited apparent sporicidal activity
against spores of toxigenic strains of Fusarium moniliforme and A. parasiticus
but not Penicillium rubrum. This sporicidal activity was evident only when spores
were exposed to an in vitro concentration of natamycin of 25 mg/liter or higher
for a period of time of at least 12 hr. The growth inhibiting activity of
natamycin was more pronounced compared with the sporicidal activity.
PMID- 11006996
TI - Detection of antibody to turkey coronavirus by antibody-capture enzyme-linked
immunosorbent assay utilizing infectious bronchitis virus antigen.
AB - An antibody-capture enzyme-linked immunosorbent assay (ELISA) for detection of
antibody to turkey coronavirus (TCV) utilizing infectious bronchitis virus (IBV)
antigen was developed. Anti-TCV hyperimmune turkey serum and normal turkey serum
were used as positive or negative control serum for optimization of the ELISA
system. Goat anti-turkey immunoglobulin G (light plus heavy chains) conjugated
with horseradish peroxidase was used as detector antibody. The performance of the
ELISA system was evaluated with 45 normal turkey sera and 325 turkey sera from
the field and the cutoff point was determined. Serum samples of turkeys
experimentally infected with TCV collected sequentially from 1 to 63 days
postinfection were applied to the established antibody-capture ELISA using IBV
antigens. The optimum conditions for differentiation between anti-TCV hyperimmune
serum and normal turkey serum were serum dilution at 1:40 and conjugate dilution
at 1:1600. Of the 325 sera from the field, 175 were positive for TCV by
immunofluorescent antibody (IFA) assay. The sensitivity and specificity of the
ELISA relative to IFA test were 93.1% and 96.7%, respectively, based on the
results of serum samples from the field turkey flocks using the optimum cutoff
point of 0.18 as determined by the logistic regression method. The ELISA values
of all 45 normal turkey sera were completely separated from that of IFA-positive
sera. The ELISA results of serum samples collected from turkeys experimentally
infected with TCV were comparable to that of the IFA assay. Reactivity of anti
rotavirus, anti-reovirus, anti-adenovirus, or anti-enterovirus antibodies with
the IBV antigens coated in the commercially available ELISA plates coated with
IBV antigens could be utilized for detection of antibodies to TCV in antibody
capture ELISA.
PMID- 11006997
TI - Morphologic observations on respiratory tracts of chickens after hatchery
infectious bronchitis vaccination and formaldehyde fumigation.
AB - The histologic changes in the respiratory tracts of chickens were evaluated after
hatchery fumigation with 40% formaldehyde vapors and vaccination against
infectious bronchitis virus with live attenuated vaccine (Massachusetts
serotype). One-day-old chickens were housed in four isolation units in controlled
environmental conditions, fed and watered ad libitum, and separated into four
groups: 1) fumigated and vaccinated birds (FV group); 2) nonfumigated and
vaccinated birds (NFV group); 3) fumigated and nonvaccinated birds (FNV group);
and 4) control group (C group). All birds were tested to be free from Mycoplasma
gallisepticum and Mycoplasma synoviae. After necropsy on the first, eighth, and
twenty-sixth days after birth, samples from tracheal upper portion and lungs were
conventionally processed for light, scanning, and transmission electron
microscopy. Tissue response was monitored by microscopic examination of trachea
and lung. On the first day of observation, fumigated and vaccinated birds (FV
group) showed extensively damaged tracheal epithelium with exfoliated areas and
some active glands with electrodense granules, and in the lung, the primary
bronchi epithelium had disorganized cilia and abundant lymphocytes, with
emphysematous areas in tertiary bronchus. On day 8 after vaccination, cubical and
cylindrical tracheal cell proliferation was observed, and on day 26, ciliated
columnar epithelium was almost regenerated with heterophil corion infiltration,
and hyaline cartilage nodules appeared in parabronchi. The nonfumigated and
vaccinated birds (NFV) revealed less injury on the epithelial surface and a more
rapid response to epithelial regeneration than the in only fumigated animals
(FNV). The control group did not show remarkable morphologic changes.
Postvaccinal and fumigation effects on the upper respiratory tract were
temporary, whereas in lungs, increased emphysema, cartilage nodules in the
interchange zone, and general lymphocyte infiltration had caused intensive
injury.
PMID- 11006998
TI - A case study on Salmonella enteritidis (SE) origin at three egg-laying farms and
its control with an S. enteritidis bacterin.
AB - In the early 1990s, three egg-laying farms (farms S, T, and B) were thought to
have the possibility of Salmonella enteritidis (SE) contamination because
positive liquid egg samples originated from those farms. The present study was
therefore conducted. The first clarification for SE contamination was the study
on the origin of SE contamination including its vertical transmission. The
results of SE contamination profiling with dust and manure, food materials, dead
embryos, and residual yolks on hatch day in regular monitoring over a few years
were clearly negative. Therefore, we concluded the SE transmission/infection was
attributed to horizontal infection in the egg-laying farms but not vertical
transmission from parental stock, hatcheries, growth, or food materials during a
7-yr experimental period. Second, we attempted to clarify if administration of an
SE bacterin (Layermune SE) to growth flocks for the egg-laying farms could reduce
SE incidence in liquid egg samples from each egg-laying farm. In the first
experiment, we compared SE incidence in liquid egg samples from vaccinated and
nonvaccinated flocks (similar age flocks). SE incidence from vaccinated and
nonvaccinated flocks showed negative and <2 most probable number (MPN)/100 ml for
farm B, <2 and >1600 MPN/100 ml for farm S, and negative and >1600 MPN/100 ml for
farm T, respectively. In the second experiment, we compared the SE isolation
incidence in the liquid egg samples from nonvaccinated and newly replaced
vaccinated flocks in the same chicken houses from each of the three egg-laying
farms. SE incidence in the liquid egg samples was similar to that in the first
experiment. Therefore, the SE bacterin may play an important role in reducing the
SE incidence of liquid egg samples.
PMID- 11006999
TI - Sequence analysis of the hemagglutinin gene of H9N2 Korean avian influenza
viruses and assessment of the pathogenic potential of isolate MS96.
AB - Sequence analysis of the hemagglutinin (HA) gene of five Korean H9N2 avian
influenza virus (AIV) isolates showed that these viruses were closely related and
possibly came from the same source. Phylogenetic analysis of the HA1 subunit of
H9 subtype isolates revealed that Korean AIV isolates were different from
isolates from the poultry markets in Hong Kong in 1997. None of the Korean AIVs
had multiple basic amino acids at the HA cleavage site that confer high
pathogenicity to some H5 and H7 AIVs. Phylogenetic analysis of the nucleoprotein
and matrix gene demonstrated that Korean isolates cluster with Eurasian origin
AIVs. The pathogenic potential of one of the isolates (MS96) was assessed after
several passages in 14-day-old embryonated chicken eggs (ECE). Fourteen-day-old
ECE derivatives of MS96 showed increased HA titer and embryo mortality in eggs;
this was apparent after the third passage in 14-day-old ECE. Sequence analysis of
the cleavage site of MS96 after the third and tenth passages in 14-day-old ECE
revealed no changes in the amino acid sequence. The pathogenicity of MS96 after
the tenth passage in 14-day-old eggs (MS96p10(ECE14)) was tested with 4-wk-old
specific-pathogen-free chickens. The 14-day-old derivative, MS96p10(ECE14),
showed wider tissue tropism and induced more severe clinical signs than the
parent virus. Furthermore, after intranasal inoculation of 86-wk-old broiler
breeders and 30-wk-old layers, the MS96p10(ECE14) derivative induced more severe
signs of depression than the parent virus as well as a transient drop in egg
production.
PMID- 11007000
TI - Protective immunity to infectious bronchitis in broilers vaccinated against
Marek's disease either in ovo or at hatch and against infectious bronchitis at
hatch.
AB - Two experiments were conducted using commercial broiler chickens to determine if
Marek's disease (MD) vaccines HVT/SB-1 and HVT plus CVI-988 given either in ovo
or at hatch adversely affected the efficacy of infectious bronchitis (IB)
vaccines (Ark and Mass serotypes) given by eyedrop on the day of hatch.
Nonvaccinated negative controls and controls that received only IB vaccines were
included in each study. Birds were challenged with either infectious bronchitis
virus (IBV) Mass-41 or IBV Ark-99 on either day 26 or 27 of age. Protection was
assessed 5 days post-IBV challenged by virus isolation from the trachea. The day
of hatch mean antibody titer to IBV was 12,668 +/- 4704 and 2503 +/- 3243 by
enzyme-linked immunosorbent assay in experiments 1 and 2, respectively. In each
study, nonvaccinated controls had a significantly higher (P < or = 0.05)
incidence (88%-100%) of IBV challenge virus isolation than did controls
vaccinated for IB but not for MD. Analysis of data from both studies showed that
protection to IB in groups that received only IB vaccines at hatch ranged from
55.0% to 77.3%, whereas protection to IB in groups receiving both MD and IB
vaccines ranged from 50.0% to 95.5%. In both experiments and within IBV challenge
serotype, broilers given MD vaccines (in ovo or at hatch) and IB vaccines at
hatch had protection rates to IBV challenges that were not significantly less (P
< or = 0.05) than IB protection rates of groups that received only IB vaccines at
hatch. Analysis of these data shows that administration of high-titered MD
vaccines either in ovo or at hatch did not affect the efficacy of an IB
vaccination (serotypes Ark and Mass) given by eyedrop at hatch.
PMID- 11007001
TI - Importance of Escherichia coli infection in ascites in broiler chickens shown by
experimental production.
AB - Common commercial strain male broilers aged 14 days were intratracheally
inoculated with 0.2 ml of 1.2 x 10(6) colony-forming units of Escherichia coli in
nutrient broth and kept in a cool environment during the experiment. Ascites was
produced in five surviving and two dead birds out of 50 but not in 50 mock
infected control birds. Among the 40 survivors that were infected, the
erythrocyte packed cell volume (PCV) of the 10 birds with pericarditis was the
same as in 21 grossly normal birds, although that of the four birds with enlarged
right ventricle (RV) was high. The pericarditis caused by E. coli septicemia was
not the primary cause of ascites. However, the PCV was high in some of the
survivors with an enlarged RV without pericarditis, indicating overload due to
the lung lesion. These data suggested that some of the birds with an enlarged RV,
caused by supplying blood that was insufficiently oxygenated for the body size,
suffered from ascites.
PMID- 11007002
TI - Ornithobacterium rhinotracheale infection in turkeys: immunoprophylaxis studies.
AB - Ornithobacterium rhinotracheale has been shown to cause serious clinical illness
and is a significant concern to the turkey industry because of its potential
economic impact. In this study, 6-wk-old turkeys were vaccinated intranasally
with a live or subcutaneously with a killed O. rhinotracheale vaccine. At 14 or
21 wk of age, the birds were challenged intratracheally with live O.
rhinotracheale. Airsacculitis and pneumonia occurred less frequently in
vaccinated birds than in unvaccinated birds after challenge with O.
rhinotracheale. Ornithobacterium rhinotracheale was recovered from unvaccinated,
challenged birds but not from vaccinated, challenged or from unchallenged birds.
Thus, turkeys inoculated with live or killed O. rhinotracheale vaccine were
protected from pathologic changes.
PMID- 11007003
TI - A comparative study of the pathogenesis of malabsorption syndrome in broilers.
AB - Five malabsorption syndrome (MAS) homogenates from The Netherlands and Germany
were used to reproduce MAS in broilers. We studied the histopathology after
inoculation of 1-day-old broiler chicks and the agents that might be involved.
Generally, the MAS homogenates induced signs that differed in severity and
pathobiology. We could distinguish and classify the inoculated groups best by
histopathology: proventriculitis, lesions in the small intestines in combination
with proventriculitis, or lesions of the small intestines only. Lesions in the
small intestine had more impact on weight gain depression than lesions in the
proventriculus. In three out of five inoculated groups, microscopic lesions of
the pancreas were found. Reovirus was detected in the inoculated groups by virus
isolation and seroconversion, and reoviral antigen was detected by
immunohistochemistry of the small intestine. Also, enteroviruslike particles were
detected in three of the five inoculated groups, although not in the most
affected group. Additionally, bacteriophages and bacteria (hemolytic Escherichia
coli, Pasteurella hemolytica, and Enterococcus durans) were isolated from
inoculated chicks. The role these agents play in pathogenesis of MAS is still
unsolved.
PMID- 11007004
TI - Emergence of subtype strains of the Arkansas serotype of infectious bronchitis
virus in Delmarva broiler chickens.
AB - Infectious bronchitis virus (IBV) field isolates of the Arkansas (Ark) serotype
were identified by reverse transcription-polymerase chain reaction (RT-PCR) as
the most common serotype isolated from 1993 to 1997. These isolates were
recovered from broiler flocks with respiratory disease raised on the Delmarva
peninsula in spite of Ark vaccination in the region. For the purposes of
investigating this apparently paradoxical finding, five RT-PCR Ark-positive field
isolates recovered in 1995 and 1996 were selected for further characterization.
The isolates were compared with Ark reference strains by reciprocal virus
neutralization (VN) in embryonated eggs, S-1 gene sequence analysis, and
challenge of immunity studies in specific-pathogen-free (SPF) chickens. Antigenic
(VN) comparisons and S-1 gene analysis confirmed that the five RT-PCR Ark
positive field isolates were of the Ark serotype but also revealed that the
viruses could be readily distinguished from Ark reference strains. Four of the
isolates (Ark/213/96, Ark/15C/96, Ark/1529/95, Ark/1534/95) were found to have
higher antigenic relatedness percentages to each other (95%-100%) than to Ark
reference strains DPI (52%-72%) and Georgia variant (Georgia var) (53%-68%) by
VN. Another isolate, Ark/1535/95, was found to differ antigenically from the
other four RT-PCR Ark-positive field isolates (34%-61%), Ark DPI (44%), and
Georgia var (43%) strains. The trends in the S-1 gene sequencing results were
similar to those observed for the VN findings. Isolates Ark/213/96, Ark/15C/96,
Ark/1529/95, and Ark/1534/95 demonstrated a higher degree of predicted S-1 amino
acid similarity to each other (96.5%-98.7%) than to Ark DPI (92.4%-93.7%), Ark 99
(93.2%-94.7%), and Georgia var (89.3%-90.8%). Ark/1535/95 S-1 amino acid
similarity values were lower compared with those of the other four RT-PCR Ark
positive field isolates (93.4%-94.8%), Ark DPI (91.9%), Ark 99 (93.0%), and
Georgia var (88.7%). Furthermore, the isolates could be distinguished from the
Ark reference strains by a characteristic sequence polymorphism, a six-nucleotide
deletion encoding amino acids 57 (Asp) and 58 (Asp) in hypervariable region 1 of
S-1. On the basis of the VN and sequencing findings, isolates Ark/213/96,
Ark/15C/96, Ark/1529/95, and Ark/1534/95 were considered to be a single subtype
of the Ark serotype. The fifth isolate, Ark/1535/95, may constitute another
subtype of the Ark serotype. Vaccination of SPF chickens with a high-titering
commercially available live vaccine containing the Ark DPI strain provided solid
protection (>90%) against challenge with the RT-PCR Ark-positive field isolates.
Immunization of SPF chickens with Ark/213/96 produced 100% protection against
challenge with the homologous strain, as well as isolates Ark/1535/95 and Ark 99
but lower levels of protection against Ark DPI (58%) and Georgia var (55%).
Primers for RT-PCR were designed to distinguish between the Ark subtypes and the
Ark reference strains on the basis of the characteristic six-nucleotide deletion
identified in the S-1 gene of the Ark subtypes. Retrospective analysis of RT-PCR
Ark-positive isolates found that the Ark subtypes existed as early as 1992 in
Delmarva broilers and became prevalent by 1995. With RT-PCR, restriction fragment
length polymorphism analysis, and DNA sequencing techniques, the presence of Ark
subtype viruses was demonstrated in two commercial Ark DPI strain vaccines and in
our Ark DPI laboratory stocks that were the original source of the virus used for
vaccine development. The demonstration of the Ark subtype and reference strains
in the Ark DPI strain is evidence of the existence of IBV quasispecies. Factors
possibly influencing the emergence of the Ark subtype in commercial broilers are
discussed.
PMID- 11007005
TI - Characterization of infectious bronchitis viruses isolated from outbreaks of
disease in commercial flocks in Brazil.
AB - Fifteen isolations of infectious bronchitis (IB) virus were made from a total of
126 Brazilian poultry flocks of all ages that were examined. These flocks (14
chicken and 1 quail) were experiencing a variety of IB-like conditions including
respiratory disease, digestive and kidney problems, and drops in egg production.
One of the isolates was of the Massachusetts serotype. The remainder were
examined by means of cross-neutralization tests in tracheal organ cultures and
were shown to belong to at least four antigenic groups, all different from ones
described previously in other countries. Some, but not all, of the flocks from
which they were isolated had been vaccinated against IB with vaccines of the
Massachusetts serotype. In vivo protection studies showed that the MA5 vaccine
(of the Massachusetts serotype) protected well against challenge with four of
these isolates, representing the different serotypes reported in this study.
PMID- 11007006
TI - Pathogenicity of a low-virulence duck virus enteritis isolate with apparent
immunosuppressive ability.
AB - Duck enteritis virus (DEV) was isolated from commercial 2-to-6-wk-old white Pekin
ducks experiencing 25%-30% mortality and high morbidity. Secondary infections
with Pasteurella multocida, Riemerella anatipestifer, and Escherichia coli were
frequently seen in affected ducks. The isolated virus was identical to the
prototype DEV by virus neutralization test but differed from the classic DEV by
causing lymphoid organ atrophy and inconsistent hemorrhagic lesions in the
intestinal annular bands. Attempts to reproduce the disease in white Pekin ducks
were unsuccessful until the virulence of the virus was increased by three
passages in Muscovy ducklings. Significant thymic atrophy (P < or = 0.001) was
detected during the first 10 days postinfection (DPI), but thymus size returned
to normal by 17-24 DPI. However, bursal atrophy increased significantly (P < or =
0.001) from 4 DPI until the end of the experiment (39 DPI). Reduction in body
weight was significant (P < or = 0.05) between 4 and 6 DPI. There was massive
depletion of thymic and bursal lymphocytes with lymphoid necrosis in the thymus,
bursa, spleen, and Harderian gland. Eosinophilic intranuclear inclusions were
observed in thymus, bursa, spleen, esophagus, cloaca, liver, conjunctiva, and
Harderian gland. Occasional intracytoplasmic inclusions were also found scattered
in the epithelial cells of conjunctiva, esophagus, bursa of Fabricius, and
cloaca. Virus was recovered from experimentally infected ducks from thymus,
bursa, spleen, liver, kidneys, trigeminal ganglion, and cloaca during the first
10 days of infection. These findings suggest that a low-virulent DEV can cause a
massive lymphoid atrophy and can sustain immunosuppression as noted by the
secondary bacterial infection.
PMID- 11007007
TI - Characterization of a small round virus associated with the poult enteritis and
mortality syndrome.
AB - A small round virus (SRV) identified and isolated in our laboratory from
intestinal samples of poults affected with the poult enteritis and mortality
syndrome was further characterized. The SRV was propagated in turkey embryos and
purified by differential and isopycnic ultracentrifugation. The size of the SRV
was 30-32 nm in diameter. The buoyant density of the SRV in cesium chloride was
between 1.34 and 1.36 g/cm3. It was resistant to chloroform treatment, stable at
pH 3.0, and resistant to heat treatment. Attempts to propagate the SRV in turkey
embryo kidney, turkey kidney, Caco-2, Vero, and BGM-70 cells were unsuccessful.
Analysis of the SRV capsid proteins by sodium dodecyl sulfate-polyacrylamide gel
electrophoresis revealed three polypeptides with molecular weights of 34.5, 31,
and 28 kD. Genome analysis of the SRV showed that the SRV had a single-strand RNA
genome about 7500 nucleotides in length. Reverse transcription-polymerase chain
reactions (RT-PCRs) with primers specific to conserved sequences of enteroviruses
yielded products with expected sizes. However, sequence analysis of the RT-PCR
products showed that there was no similarity between the sequences and that of
enteroviruses. RT-PCR with primers specific to the 3' end of a SRV RNA genome
yielded products with expected sizes. These products were sequenced and found to
contain 669 nucleotides, excluding the polyadenylated tail. Sequence analysis
indicated that the SRV shared 38.18% amino acid identity in the C-terminal capsid
precursor protein and 41.26% nucleotide identity of the 3' end of turkey
astrovirus RNA genome (Genbank accession no. Y15936). We concluded that the SRV
is a member of the astrovirus family.
PMID- 11007008
TI - Significance of infectious bursal disease serology in an integrated quality
control program under European epidemiologic conditions.
AB - In this study performed between 1993 and 1997, infectious bursal disease virus
(IBDV) antibody titers and performance data were recorded in a vertically
integrated monitoring scheme in order to make a follow-up from day-old parents
down to the broilers at slaughter. All measured data were used two by two in a
simple correlation study to calculate the degree to which they were linearly
correlated. It appeared that high and/or uniform antibody titers in the parents
were correlated with increased daily weight gain and decreased mortality and
slaughterhouse condemnation in the broilers. Antibody titers and their CVs were
negatively correlated in broiler parents and their offspring at day-old and even
at slaughter. Results indicate that high and uniform antibody titers against IBDV
in broiler parents are important for good performance of the broiler offspring,
at least under the epidemiologic conditions of this study, which included the
presence of very virulent IBDV strains in the field and the sole use of live
intermediate vaccines in broilers as well as broiler parents.
PMID- 11007009
TI - The effects of ts-11 strain Mycoplasma gallisepticum vaccination in commercial
layers on egg production and selected egg quality parameters.
AB - Live Mycoplasma gallisepticum (MG) vaccines have been USDA approved and licensed
for use in commercial layer chickens since 1988; however, egg production and egg
quality data exist only for the F strain of MG. Information pertinent to the
effects of ts-11 MG on egg and eggshell quality parameters, as well as egg size
distribution, is lacking. In this study, pullets were inoculated at 10 wk of age
with ts-11 strain MG and placed in biological isolation units at 10 birds/unit.
Hen-day egg production, eggshell strength, Haugh unit score, pimpling incidence,
and blood/meat spot incidence were monitored and recorded in each trial through a
45-wk production cycle. Further, eggs from all treatments were collected daily,
Monday-Thursday, and individually weighed. Results of this study indicate that no
significant difference was observed between the treatments for the parameters
measured or for egg size distribution. Therefore, these data should lessen
producers' concerns pertaining to the impact of ts-11 strain MG on egg
production, egg and eggshell quality parameters, and egg size distribution.
PMID- 11007010
TI - Comparison of virus isolation, immunohistochemistry, and reverse transcriptase
polymerase chain reaction procedures for detection of turkey coronavirus.
AB - A reverse transcriptase-polymerase chain reaction (RT-PCR) procedure and two
monoclonal antibody (MAb)-based immunohistochemical procedures were developed for
detection of turkey coronavirus (TCV) in tissues and intestinal contents/dropping
samples. The RT-PCR, MAb-based fluorescent antibody (FA), and MAb-based
immunoperoxidase (IP) procedures were compared with virus isolation (VI) for
detection of TCV in experimentally infected turkeys. TCV was detected in
experimentally infected turkeys as early as day 1 postexposure (PE) by each of
the four detection procedures. TCV was detected as late as day 35 PE by FA or IP
and days 42 and 49 PE by VI and RT-PCR, respectively. With VI as a reference,
sensitivity and specificity of RT-PCR were 93% and 92%, respectively; specificity
of both FA and IP was 96%, and sensitivities were 69% and 61%, respectively. Each
of the examined procedures was highly specific, but the RT-PCR procedure was also
highly sensitive. These findings demonstrate the utility of both
immunohistochemistry and RT-PCR for detection of TCV. In addition, the findings
indicate that RT-PCR is a highly sensitive and specific alternative to
conventional diagnostic procedures.
PMID- 11007011
TI - The commercial production of specific-pathogen-free eggs and chickens: the
evolution of an industry.
PMID- 11007012
TI - The history of avian reovirus.
PMID- 11007014
TI - Redesign of primer and application of the reverse transcriptase-polymerase chain
reaction and restriction fragment length polymorphism test to the DE072 strain of
infectious bronchitis virus.
AB - Diagnosis of the DE072 strain of infectious bronchitis virus (IBV) by the reverse
transcriptase-polymerase chain reaction (RT-PCR) and restriction fragment length
polymorphism (RFLP) serotype identification test was not possible because the
primer used in the RT-PCR did not amplify the S1 gene of the DE072 strain. The 3'
end of the polymerase gene and the 5' end of the S2 gene of the DE072 strain were
sequenced and compared with the forward and reverse RT-PCR primers, respectively.
A 2-bp mismatch at the 3' end of the reverse primer was found. On the basis of
these data, a degenerate primer that could amplify the S1 gene of the DE072
strain as well as eight other serotypes of the virus was synthesized. In
addition, we were able to differentiate the DE072 strain from all of the other
IBV strains examined by RFLP analysis of the RT-PCR product.
PMID- 11007013
TI - Pathogenicity of West Nile virus in chickens.
AB - In the fall of 1999, West Nile virus (WNV) was isolated for the first time in the
Western Hemisphere during an outbreak of neurologic disease in humans, horses,
and wild and zoo birds in the northeastern United States. Chickens are a
potential reservoir for WNV, and little is known about the pathogenicity of WNV
in domestic chickens. Seven-week-old chickens derived from a specific-pathogen
free flock were inoculated subcutaneously with 1.8 x 10(3) 50% tissue culture
infectious dose of a crow isolate of WNV in order to observe clinical signs and
evaluate the viremic phase, gross and microscopic lesions, contact transmission,
and immunologic response. There were no observable clinical signs in the WNV
inoculated chickens during the 21-day observation period. However,
histopathologic examination of tissues revealed myocardial necrosis, nephritis,
and pneumonitis at 5 and 10 days postinoculation (DPI); moderate to severe
nonsuppurative encephalitis also was observed in brain tissue from one of four
inoculated birds examined at 21 DPI. WNV was recovered from blood plasma for up
to 8 DPI. Virus titers as high as 10(5)/ml in plasma were observed at 4 DPI.
Fecal shedding of virus was detected in cloacal swabs on 4 and 5 DPI only. The
WNV also was isolated from myocardium, spleen, kidney, lung, and intestine
collected from chickens euthanatized at 3, 5, and 10 DPI. No virus was isolated
from inoculated chickens after 10 DPI. Antibodies specific to WNV were detected
in inoculated chickens as early as 5 DPI by the plaque reduction neutralization
test and 7 DPI by the indirect fluorescent antibody test. Chickens placed in
contact with inoculated chickens at 1 DPI lacked WNV-specific antibodies, and no
WNV was isolated from their blood plasma or cloacal swabs throughout the 21 days
of the experiment.
PMID- 11007015
TI - Newcastle disease and avian influenza A virus in wild waterfowl in South Africa.
AB - In an intensive ostrich farming area in South Africa with a history of ostrich
influenza outbreaks, we conducted a survey of avian influenza virus (AIV) and
Newcastle disease virus (NDV) in wild aquatic birds. During late autumn and
winter 1998, the time of year when outbreaks in ostriches typically start to
occur, 262 aquatic birds comprising 14 species were sampled and tested for both
virus infections. From eight samples, AIV, serotype H10N9, could be isolated. All
isolates were apathogenic as determined by the intravenous pathogenicity index
(0.00). Conversely, none of 33 sera of these wild birds showed antibodies against
H10. However, one bird was found serologically positive for H6 AIV. This AIV
serotype was later isolated from ostriches during an avian influenza outbreak in
this area. No NDV was isolated although 34 of 46 serum samples contained NDV
specific antibodies. This is the first H10N9 isolate to be reported from Africa.
In addition, our data support the notion that wild aquatic birds may function as
a reservoir for AIV and NDV in South Africa.
PMID- 11007016
TI - Humoral immune responses to chicken infectious anemia virus in three strains of
chickens in a closed flock.
AB - This is a comparative study on seroconversion to chicken infectious anemia virus
(CIAV) in a closed flock of specific-pathogen-free chickens undergoing a natural
outbreak and after vaccination of some of these flocks with a commercial, live
vaccine. The N2a strain (B21B21 haplotype) had the highest seroconversion after
natural infection (94%) or vaccination (100%), followed by the P2a strain
(B19B19) at 75%-82% seroconversion after natural infection and 85% seroconversion
after vaccination. The S13 (B13B13) chickens were 26% seropositive after natural
infection and 75% seropositive after vaccination. N2a chickens with polymerase
chain reaction (PCR)-positive tissues were 97% seropositive compared to 80%-83%
PCR-positive and seropositive for the P2a chickens and only 8% seropositive and
PCR-positive for the S13 chickens. Seroconversion occurred at or near sexual
maturity after natural infection in seven flocks studied.
PMID- 11007018
TI - Bumblefoot and lack of exercise among wild and captive-bred falcons tested in the
United Arab Emirates.
AB - In the 1990s, bumblefoot posed a major health problem to the falcons in the
United Arab Emirates. This retrospective study based on statistical field
research showed that in captivity wild falcons need a training frequency of twice
a day to reduce the bumblefoot morbidity rate. In this context, they responded
very well to free flight in aviaries during the molting season. In contrast,
captive-bred falcons did not show a highly significant difference regarding
training frequencies. Wild falcons tested fed with pigeons, bustards, and ducks
suffered significantly less from bumblefoot compared with those fed a diet of
quail. Apart from the disease-reducing impact of beef and mice, captive-bred
falcons tested did not show any significant difference regarding the influence of
diet on the bumblefoot occurrence.
PMID- 11007017
TI - Drag swab efficiency factors when sampling chicken manure.
AB - This study examines drag swabbing distance, media for moistening the drag swabs,
and site selection when sampling a laying facility by drag swabbing manure piles.
Manure piles at a laying facility in California's San Joaquin Valley were sampled
with drag swabs over various distances. Samples were cultured for Salmonella spp.
with standard laboratory methods, and most probable number calculations.
Salmonella spp. counts were expected to be highly variable because of reported
clustering. Therefore, total bacteria and Escherichia coli, which were assumed to
have a more uniform distribution on the surface of the manure, were additionally
used as proxies for Salmonella. Media for moistening the swabs were compared by
seeding postswabbing samples with Salmonella typhimurium, and culturing at
different delay times. Total bacterial counts were compared between samples that
were obtained from either wet or dry surfaces. Numbers of Salmonella spp. and
total bacteria peaked within 120 feet of swabbing distance. Higher total bacteria
counts were obtained by swabbing wet areas rather than dry areas, but the
distance that could be swabbed effectively was shorter in wet areas. Moistening
media selected for the swab resulted in statistically different culture counts,
but did not show any important difference in maintaining Salmonella viability
over a 48-hr period when the samples were kept at refrigerated temperatures. Once
swabs became fully loaded with fecal material, bacterial numbers failed to
increase with further use. Overuse of a swab may result in failure to detect
Salmonella enteritidis on chicken manure if the distribution of this organism is
clustered.
PMID- 11007019
TI - The sensitivity and specificity of a reverse transcription-polymerase chain
reaction assay for the avian pneumovirus (Colorado strain).
AB - A reverse transcription-polymerase chain reaction (RT-PCR) assay for the
detection of avian pneumovirus (APV), Colorado strain (US/CO), was evaluated for
sensitivity and specificity. The single-tube RT-PCR assay utilized primers
developed from the matrix (M) gene sequence of the US/CO APV. The RT-PCR
amplified the US/CO APV but did not amplify other pneumoviruses, including the
avian pneumoviruses subgroups A and B. The RT-PCR was capable of detecting
between 10(0.25) mean tissue culture infective dose (TCID50) and 10(-0.44) TCID50
of the US/CO APV. These results have demonstrated that the single-tube RT-PCR
assay is a specific and sensitive assay for the detection of US/CO APV.
PMID- 11007020
TI - Characterization of a lentogenic Newcastle disease virus isolated from broiler
chickens in Japan.
AB - Newcastle disease virus (NDV), named MET95, was isolated from a non-vaccinated
broiler flock in Japan in 1995. The MET95 strain was determined to be a
lentogenic NDV. The strain has the properties of eluting rapidly at 4 C and has
low thermostability in hemagglutinating activity with chicken erythrocytes. In
these studies, no difference could be found between the MET95 strain and the
Hitcher B1 vaccine strain. However, the chickens inoculated with the MET95
strain, as well as chickens that they were in contact with, had a much higher
hemagglutination-inhibition antibody response than those inoculated with the B1
strain. Accordingly, the MET95 strain is thought to be a promising candidate as a
live ND vaccine strain. In Japan, this is the first report on the isolation of
lentogenic NDV from chickens since the paper on the Ishii strain isolated in
1966.
PMID- 11007021
TI - Sequence of precursor polyprotein gene (segment A) of infectious bursal disease
viruses isolated in Korea.
AB - The coding regions of segment A of two recent Korean very virulent (vv)
infectious bursal disease virus (IBDV) isolates (KK1 and KSH) and one atypical
IBDV isolate (K310) were amplified by reverse transcriptase-polymerase chain
reaction, sequenced, and compared with published sequences for IBDV. The overall
amino acid sequence similarity of the KK1 and KSH strains compared with foreign
vvIBDV strains was between 97.43% and 98.02%. The KK1 and KSH strains, like
vvIBDV strains, share unique amino acid residues at positions 222(A), 256(I),
294(I), and 299(S). The sequence of K310 strain was markedly different from other
IBDV strains. The K310 strain had 12, 2, and 1 unique amino acid substitutions in
the VP2 hypervariable region, VP4, and VP3 gene, respectively, and 3 of 12
substitutions in a VP2 hypervariable region were found in two hydrophilic regions
known to be involved in antigenic determination. Also, the K310 strain had 222(S)
and 254(S), which were found in variant IBDV strains. The SWSASGS heptapeptide is
conserved in all Korean IBDV isolates. By phylogenetic analysis, KK1 and KSH were
categorized in one group with foreign vvIBDV isolates, but K310 isolate was
categorized in a separate group that was differentiated from the other IBDV
strains compared. The K310 strain seemed to be evolved from a separate lineage of
IBDV strain.
PMID- 11007022
TI - Preparation of a heterogeneous conjugate to detect Mycoplasma iowae by
immunofluorescence.
AB - Fluorescent antibody technique has been used as a diagnostic tool for the
identification of pathogenic avian Mycoplasma species. Fluorescein-conjugated
antisera for Mycoplasma iowae prepared from rabbit hyperimmune serum against one
serotype (I) has not always been reliable, giving false-negative results. A
fluorescein-conjugated antisera was prepared with antibody against the six
identified serotypes (I, J, K, N, Q, and R) that comprise the species M. iowae.
This heterogeneous conjugate was used to positively identify M. iowae in field
isolates and lab strains, while maintaining specificity. Polymerase chain
reaction specific for M. iowae was used to determine specificity.
PMID- 11007023
TI - The effect of vitamin E on cellulitis in broiler chickens experiencing scratches
in a challenge model.
AB - Two experiments are described; each experiment contained five treatments with
each treatment consisting of a specific diet and vitamin E at 8.82 mg, 41.89 mg,
74.96 mg, 108.03 mg, or 141.10 mg vitamin E per kilogram of feed. Birds were
raised with continuous feed containing the various levels of vitamin E available
throughout the experiment. At 4 wk of age, the birds were scratched on the breast
and placed onto avian cellulitis Escherichia coli-seeded litter. One week later,
the birds were euthanatized and lesion presence was noted. There appeared to be a
positive correlation between vitamin E and the inhibition of cellulitis formation
when the birds were fed a diet containing 74.96 mg vitamin E/kg feed. Conflicting
results were seen in the two experiments when the birds were fed 41.89 and 108.03
mg vitamin E/kg feed. Both experiments had a high incidence of cellulitis in
birds whose diets consisted of 141.10 mg vitamin E/kg feed.
PMID- 11007024
TI - Deposition of phage type 4 and 13a Salmonella enteritidis strains in the yolk and
albumen of eggs laid by experimentally infected hens.
AB - Because egg yolk and albumen differ substantially in their abilities to support
bacterial growth, the initial level and location of Salmonella enteritidis
deposition are critical for determining whether proposed standards for
refrigerating eggs are likely to protect public health by preventing extensive
microbial multiplication. In the present study, three groups of laying hens were
infected with oral doses of approximately 10(9) cells of different S. enteritidis
strains (two were phage type 4 and one was phage type 13a) in two replicate
trials. For all three S. enteritidis strains, the incidence of yolk contamination
(approximately 2.5% overall) was significantly greater than the incidence of
albumen contamination (approximately 0.5% overall). The phage type 13a strain was
less often isolated from fecal samples at 2 wk post-inoculation than were the
phage type 4 strains, but no significant differences between strains were
observed in the incidence of egg contamination. Most freshly laid contaminated
eggs contained fewer than 1 S. enteritidis cell/ml of egg yolk or albumen, and no
sample contained more than 67 S. enteritidis cells/ml.
PMID- 11007025
TI - Eimeria brunetti and Eimeria necatrix in chickens of Argentina and confirmation
of seven species of Eimeria.
AB - Ten poultry farms (broiler breeder pullets, layer pullets, and broilers) in the
provinces of Entre Rios and Buenos Aires in Argentina were examined for presence
of Eimeria spp. Litter samples obtained from flocks 7-11 wk old were taken to the
laboratory for oocyst counting and sporulation, then concentrated for inoculation
into coccidia-free chickens. Species were identified by prepatent period, oocyst
size, location and appearance of lesions in the intestine, microscopic
examination of mucosal smears, and histology (to confirm Eimeria brunetti). On
this basis, Eimeria praecox was found in two samples, Eimeria mitis in two,
Eimeria acervulina in nine, Eimeria maxima in seven, Eimeria necatrix in three,
Eimeria tenella in seven, and E. brunetti in four. These results confirm the
presence of all seven recognized species of Eimeria in chickens in the Republic
of Argentina.
PMID- 11007026
TI - Determination of the incidence of Salmonella spp., Campylobacter jejuni, and
Clostridium perfringens in wild birds near broiler chicken houses by sampling
intestinal droppings.
AB - Several methods were evaluated for collecting fecal and intestinal samples from
wild birds found near broiler chicken houses. A few intestinal samples and
cloacal swabs were obtained from European starlings and house sparrows. Most of
the samples collected consisted of wild bird droppings found on or near the
houses. Samples were collected from each of four farms of a broiler integrator
during a grow-out cycle: a cycle in the summer for farm A, fall for farm B, and
spring, summer, fall, and winter for farms C and D. Of the 25 wild bird
intestinal and fecal samples collected from a broiler house on farm A during a
grow-out cycle in July-August 1997, 24% were positive for Salmonella spp., 4% for
Campylobacter jejuni, and 28% for Clostridium perfringens. Of the nine fecal
samples collected from broiler house B in a grow-out cycle in September-November
1997, 33% were positive for Salmonella spp., 11% for C. jejuni, and 22% for C.
perfringens. For farms C and D, of the 23 samples collected in March-April 1998,
0 were positive for Salmonella spp., 11% for C. jejuni, and 52% for C.
perfringens; of 27 samples collected in June-July 1998, 4% were positive for
Salmonella spp., 0 for C. jejuni, and 13% for C. perfringens; of 24 samples
collected in August-October 1998, 14% were positive for Salmonella spp., 5% for
C. jejuni, and 4% for C. perfringens; of 14 samples collected December 1998
January 1999, 0 were positive for Salmonella, 50% for C. jejuni, and 14% for C.
perfringens. The incidence of these bacterial enteropathogens in wild birds near
the broiler chicken houses suggests that wild birds that gain entry to poultry
grow-out houses have the potential to transmit these pathogens to poultry.
PMID- 11007027
TI - An outbreak of erysipelas in 2-day-old poults.
AB - Systemic erysipelas infection was seen in 2-to-4-day-old poults from three
separate ranches owned by the same company. The affected poults were all from the
same breeder source; poults from other breeder sources were seemingly unaffected.
Mortality increased on days 2 and 3, ranging from 2% to 8.5%. Birds submitted
were dehydrated and very weak, with one half of the poults submitted having died
during transport to the lab. Gross lesions included swollen, congested livers and
spleens, as well as hemorrhagic breast muscle in one case. Toes were swollen and
reddish-purple in color. The poults had been toe-trimmed during hatchery
processing using a commercial microwave. Histologically, periportal inflammation
with heterophilic infiltration in the liver was noted. Spleens showed
hyalinization of arteries, lymphoid depletion, and necrosis. Toe joints showed
purulent synovitis and cellulitis. Gram stains done on impression smears of liver
and spleen showed rare to moderate numbers of small gram-positive rods.
Erysipelothrix rhusiopathiae was isolated from 18 of 22 livers cultured, five of
six toe joints cultured, and from the yolk sac in two birds.
PMID- 11007028
TI - Ornithobacterium rhinotracheale infection in commercial laying-type chickens.
AB - Ornithobacterium rhinotracheale is a gram-negative, rod-shaped, pleomorphic
bacterium that has been isolated from flocks of turkeys and broilers from around
the world. Infections cause respiratory disease, mortality, and growth
suppression, or clinical signs of infection may be absent. In layers, there have
been few reports of disease caused by O. rhinotracheale. This is the first report
of O. rhinotracheale infection in United States layer flocks.
PMID- 11007029
TI - Turkey knockdown in successive flocks.
AB - Turkey knockdown was diagnosed in three of five flocks of hen turkeys on a single
farm within a 12-mo period. The age of birds in the flocks affected ranged from 6
wk 2 days to 7 wk 4 days. The attack rate ranged from 0.02% to 0.30% with a case
fatality rate in affected birds ranging from 0 to 74%. The diagnosis was made on
the basis of clinical signs and histopathologic lesions associated with
knockdown. The feed in all flocks contained bacitracin methylene disalicylate and
monensin (Coban). Affected birds were recumbent, demonstrated paresis, and were
unable to vocalize. Postmortem examination revealed few significant lesions
although pallor of the adductor muscles and petechiation in adductor and
gastrocnemius muscles were noted. Birds that had been recumbent for extended
periods were severely dehydrated. Consistent microscopic lesions included
degeneration, necrosis, and regeneration of adductor, gastrocnemius, and
abdominal muscles. No lesion in cardiac tissue was noted. Results of our
investigation indicated that changes in water consumption, vitamin E status, and
brooder to finisher movement correlated with the occurrence of knockdown. Turkey
knockdown was defined in 1993 as any condition identified in a turkey flock that
has affected the neuromuscular system to a degree that a turkey is unable to walk
or stand. This definition was later modified to...neuromuscular or skeletal
systems to a degree that a turkey is unable to walk or stand properly. Knockdown
may be associated with numerous feed, management, or disease factors alone or in
combination. Dosage of monensin, feed restriction/gorging, water restriction,
heat stress, copper, mycotoxins, sodium chloride in feed, and sulfa drugs have
all been suggested as contributing factors; however, laboratory studies to
duplicate this have not been successful. This report presents observations from a
single farm at which three of five hen flocks in a single year experienced
knockdown. When a flock was reported as affected, a detailed investigation was
initiated within 3 hr. The fifth flock was followed on a twice weekly basis from
0 to 8 wk of age to determine if initiating events were evident, but knockdown
did not occur.
PMID- 11007030
TI - Isolation of avian influenza virus (H10N7) from an emu (Dromaius novaehollandiae)
with conjunctivitis and respiratory disease.
AB - Avian influenza virus was isolated from the conjunctiva of a male emu chick.
Clinical observations included ocular discharge, dyspnea, and mild respiratory
signs. Lesions included conjunctivitis, tracheitis, bronchopneumonia, and
airsacculitis. Escherichia coli was isolated from the conjunctiva and the sinus,
and Staphylococcus sp. was isolated from the conjunctiva. Influenza A viral
nucleoprotein was detected immunohistochemically in epithelial cells of the
bronchi, lung parenchyma and tracheal mucosa, and mononuclear inflammatory cells
within the exudate of the bronchial lumen; conjunctiva, air sacs, kidney,
intestine, and liver were negative for the viral nucleoprotein. The isolated
influenza virus was typed as H10N7 and was determined to be nonpathogenic for
chickens.
PMID- 11007031
TI - Expression of matrix metalloproteinase-1 in human colorectal carcinoma.
AB - Matrix metalloproteinases are considered to play an important role in tumor
invasion and metastasis. To elucidate the involvement of MMP-1 in human
colorectal carcinoma, we performed immunohistochemical analysis on tissues from
20 colorectal adenomas and 142 colorectal adenocarcinomas, including 27
intramucosal carcinomas and 115 invasive carcinomas. MMP-1 was not expressed in
any of the 20 cases of colorectal adenoma examined. In contrast, 108 of 142 cases
(76.1%) with colorectal adenocarcinoma showed immunoreactivity for MMP-1 in the
carcinoma cells themselves. Expression of MMP-1 was also identified in stromal
cells around the carcinoma. We investigated the relationship between pathological
features in colorectal carcinoma and MMP-1 immunoreactivity of the tumor cells.
MMP-1 expression was less frequent in intramucosal carcinomas and weaker than
that in invasive carcinomas (P < .0001). Among the 115 cases of invasive
carcinomas, MMP-1 immunoreactivity was significantly correlated with the depth
grading of tumor invasion (P < .05), tumor growth pattern (P < .05), the presence
of lymphatic invasion (P < .05), venous invasion (P < .05), neural invasion (P <
.05), lymph node metastasis (P < .005), hepatic metastasis (P < .05), and
increasing stages of Dukes' classification (P < .05). In situ hybridization,
using an MMP-1 oligonucleotide probe, confirmed the presence of MMP-1 mRNA in
colorectal carcinoma cells themselves. Expression of MMP-1 mRNA was detected by
the reverse transcription polymerase chain reaction method in cultured human
colorectal carcinoma cell lines and colon carcinoma tissue obtained at surgery.
These findings suggest that the expression of MMP-1 is one of the important
factors related to tumor invasion and metastasis in colorectal carcinoma.
PMID- 11007032
TI - Nodular amyloidoma and primary pulmonary lymphoma with amyloid production: a
differential diagnostic problem.
AB - Nodular amyloidomas (NA) of the lung are non-neoplastic inflammatory nodules
containing eosinophilic amyloid deposits and a lymphoplasmacytic infiltrate. In
some instances, the extensive amyloid deposits may obscure an underlying
lymphoproliferative disorder. The histologic and immunohistologic features that
discriminate these two differential diagnostic possibilities were studied in this
series of six cases of NA and five cases of primary low-grade malignant lymphomas
of lung with secondary amyloid deposits (ML). Two of lymphoma cases showed
histopathologic and immunophenotypic features of B-cell chronic lymphocytic
leukemia/small lymphocytic lymphoma (B-cell CLL/SLL), and three cases were low
grade B-cell lymphoma derived from mucosa associated lymphoid tissue (MALT
lymphoma). Key discriminating morphologic features between NA and ML included
lymphatic tracking of the cellular infiltrate (3/5 ML; 1/6 NA), pleural
infiltration (3/5 ML; 0/6 NA), sheet-like masses of plasma cells (5/5 ML; 0/6 NA)
and reactive follicles (4/5 ML; 1/6 NA). Lesional circumscription, vascular and
bronchial destruction, lymphoepithelial lesions, and granulomas were not helpful
discriminators. Immunohistochemical features indicating a dominant CD20+, CD79a+
B-cell population (5/5 ML; 0/6 NA), light chain restriction (4/5 ML; 0/6 NA), and
aberrant antigen expression of CD20/CD43 (2/5 ML; 0/6 NA) were helpful. Amyloid
tumors with a reactive lymphoplasmacytic infiltrate can be separated from low
grade malignant lymphomas utilizing both histologic and immunohistochemical
features.
PMID- 11007033
TI - What levels of agreement can be expected between histopathologists assigning
cases to discrete nominal categories? A study of the diagnosis of hyperplastic
and adenomatous colorectal polyps.
AB - AIMS: To assess the levels of agreement between histopathologists for a two-class
nominal categorization process--the discrimination between hyperplastic and
adenomatous colorectal polyps. METHODS: Fifty hyperplastic and 50 adenomatous
polyps received consecutively in the laboratory were categorized by nine
histopathologists, and the level of agreement between all observers and the
original diagnosis was assessed using kappa statistics. RESULTS: For the eight
observers with 11 months or more experience in histopathology, there was a high
level of agreement with kappa statistics ranging from 0.84 to 0.98. This process
was performed rapidly with an average of 13 to 22 seconds spent on each case. One
observer with only 6-weeks' experience of histopathology had a lower overall
level of agreement with kappa statistics ranging from 0.46 to 0.54, but the
performance on the later cases was much higher. CONCLUSIONS: The level of
agreement in the distinction between hyperplastic and adenomatous colorectal
polyps is high among histopathologists with at least moderate amounts of
experience in histopathology. The one virtually naive observer showed a marked
learning response during the study without feedback on case outcome. This
suggests that histopathologists are very reliable in assigning cases to distinct
nominal categories and that learning of these processes occurs early in a
histopathologist's career.
PMID- 11007034
TI - Abnormal expression of cell cycle regulatory proteins in ductal and lobular
carcinomas of the breast.
AB - In a previous study, we demonstrated that the G1 cell cycle checkpoint in
carcinomas of the breast is frequently abrogated by loss of p16, the product of
the CDKN2/INK4A gene, and, to a lesser extent, by loss of pRB, the product of the
retinoblastoma gene. The purpose of the present study was to determine whether
other mechanisms of cell cycle deregulation exist in breast cancers which have
retained RB and p16 function. Paraffin sections of 81 invasive breast carcinomas
(49 ductal, 26 lobular, 6 mixed) were reacted with monoclonal antibodies against
cyclin D1 and p53, using optimized immunohistochemical staining protocols. The
staining results were correlated with the expression of p16 and pRB, and with a
variety of pathological parameters and DNA ploidy. Twenty-five tumors (31%)
accumulated (presumably mutant) p53 and 28 (35%) overexpressed cyclin D1; 7
carcinomas (not including any pure lobular cancers) abnormally expressed both
proteins. p53 accumulation correlated with nuclear, mitotic, and overall grade,
but not with tumor size, lymph node involvement, or DNA ploidy. Overexpression of
cyclin D1 was not associated with any of the patho-biological variables. There
was an inverse correlation between loss of p16 and high levels of p53, but not
cyclin D1. The G1 cell cycle checkpoint, which is controlled by RB, cyclin D1,
and p16, was abrogated in 65% of carcinomas, and only p53 was abnormal in an
additional 17%. The number of abnormally expressed genes correlated with mitotic
activity and overall tumor grade, but not with tumor histology, size, or nodal
status, suggesting that cell cycle deregulation is an early event in breast
tumorigenesis. Only 18% of the carcinomas showed a normal level of expression of
the four genes tested, and p16 appeared to be the most common target of cell
cycle deregulation. These data point to the importance of cell cycle regulatory
protein abnormalities in human breast cancer.
PMID- 11007036
TI - Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of
435 cases.
AB - Cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) are low molecular weight
cytokeratins. Their anatomic distribution is generally restricted to epithelia
and their neoplasms. We surveyed 435 epithelial neoplasms from various organ
systems by immunohistochemistry using CK 7 and CK 20 monoclonal antibodies.
Expression of CK 7 was seen in the majority of cases of carcinoma, with the
exception of those carcinomas arising from the colon, prostate, kidney, and
thymus; carcinoid tumors of the lung and gastrointestinal tract origin; and
Merkel cell tumor of the skin. The majority of cases of squamous cell carcinoma
of various origins were negative for CK 7, except cervical squamous cell
carcinoma, in which 87% of cases were positive. Approximately two thirds of cases
of malignant mesothelioma were CK 7-positive. CK 20 positivity was seen in
virtually all cases of colorectal carcinomas and Merkel cell tumors. CK 20
positive staining was also observed in cases of pancreatic carcinomas (62%),
gastric carcinoma (50%), cholangiocarcinomas (43%), and transitional cell
carcinomas (29%). The expression of CK 20 was virtually absent in carcinomas from
other organ systems and in malignant mesothelioma. CK 7- and CK 20-negative
epithelial neoplasms included adrenal cortical carcinoma, germ cell tumor,
prostate carcinoma, renal cell carcinoma, and hepatocellular carcinoma.
PMID- 11007035
TI - Pathologic, cytogenetic and molecular assessment of acute promyelocytic leukemia
patients treated with arsenic trioxide (As2O3).
AB - Arsenic trioxide (As2O3) shows great promise as an effective therapy for patients
with all-trans retinoic acid (ATRA)-resistant acute promyelocytic leukemia (APL).
Little data is available addressing the pathology of As2O3 treated APL and
whether the antileukemic mechanism of As2O3 is primarily cytolysis or through
stimulation of cell differentiation. In this report, we made a morphologic,
cytogenetic, and molecular evaluation of five ATRA-refractory APL patients who
were treated with As2O3. Four of the five patients had morphologic responses
after one or two cycles of As2O3 treatment. Of the four responders based on bone
marrow morphology, two achieved molecular remission (negative RT-PCR for PML- RAR
alpha fusion transcripts) by the end of the second and third cycles of As2O3
therapy. Two patients exhibited marked leukocytosis during the first cycle of
As2O3, and at that time point the APL cells were largely replaced by the cells
showing partial differentiation towards myelocytes with co-expression of CD11b
and CD33. Nevertheless, these "myelocyte-like" cells that showed the t(15;17)
translocation eventually disappeared with continuous As2O3 therapy. As2O3
treatment appears to be effective therapy for the patients with relapsed APL
after the failure of conventional chemotherapy and ATRA therapy. The pathologic
findings in these five cases suggest that at low doses As2O3 primarily induces
differentiation of the APL cells, generating abnormal myelocytes resembling APL
cells treated with ATRA, whereas at higher doses AS2O3 induces marrow necrosis.
PMID- 11007037
TI - Missense mutation of the MET gene detected in human glioma.
AB - Multiple mechanisms, such as gene mutations, amplifications, and rearrangements,
as well as perturbed mitogen and receptor function, are likely to contribute to
glioma formation. The MET (also known as c-met proto-oncogene located at 7q31-34
has been shown to be amplified in human gliomas, and activating mutations within
the tyrosine kinase domain of MET have been causally related to tumorigenesis in
hereditary papillary renal cell carcinoma. To elucidate the role of MET gene in
glioma formation, sporadic gliomas from 11 patients were examined for MET gene
mutations and allelic duplications or deletions by polymerase chain reaction
single strand conformational polymorphism analysis and fluorescence in situ
hybridization. Three of 11 sporadic gliomas showed a deletion of one copy of the
MET gene, and a specific METgene missense mutation in the remaining gene copy was
detected in one of those tumors. The corresponding sequence in non-tumor DNA was
normal in all cases. Three of 11 sporadic gliomas showed duplication of one copy
of the MET gene, but none of them contained mutations. One tumor showed
METamplification without mutation. Three showed neither allelic change nor
mutation. These data suggest that somatic MET gene mutation may play a role in
the development of a subgroup of sporadic gliomas. However, MET mutations appear
to be absent in the majority of sporadic gliomas.
PMID- 11007038
TI - Splenic angiosarcoma: a clinicopathologic and immunophenotypic study of 28 cases.
AB - Primary angiosarcoma of the spleen is a rare neoplasm that has not been well
characterized. We describe the clinical, morphologic, and immunophenotypic
findings of 28 cases of primary splenic angiosarcoma, including one case that
shares features of lymphangioma/lymphangiosarcoma. The patients included 16 men
and 12 women, aged 29 to 85 years, with a mean of 59 years and median of 63
years. The majority of patients (75%) complained of abdominal pain, and 25%
presented with splenic rupture. The most common physical finding was splenomegaly
(71%). Seventeen of 21 patients were reported to have anemia. Macroscopic
examination showed splenomegaly in 85% cases. Sectioning revealed discrete
lesions in 88% of cases, ranging from well-circumscribed firm nodules to poorly
delineated foci of necrosis and hemorrhage associated with cystic spaces.
Microscopically, the tumors were heterogenous; however, all cases demonstrated at
least a focal vasoformative component lined by atypical endothelial cells. Solid
sarcomatous, papillary, and epithelioid growth patterns were observed. The solid
sarcomatous component resembled fibrosarcoma in two cases and malignant
fibroushistiocytoma in one case. Hemorrhage, necrosis, hemosiderin,
extramedullary hematopoiesis, and intracytoplasmic hyaline globules were
frequently identified. A panel of immunohistochemical studies revealed that the
majority of tumors were immunoreactive for at least two markers of vascular
differentiation (CD34, FVIIIRAg, VEGFR3, and CD31) and at least one marker of
histiocytic differentiation (CD68 and/or lysozyme). Metastases developed in 100%
of patients during the course of their disease. Twenty-six patients died of
disease despite aggressive therapy, whereas only two patients are alive at last
follow-up, one with disease at 8 years and the other without disease at 10 years.
In conclusion, primary splenic angiosarcoma is an extremely aggressive neoplasm
that is almost universally fatal. The majority of splenic angiosarcomas coexpress
histiocytic and endothelial markers by immunohistochemical analysis, which
suggest that some tumors may originate from splenic lining cells.
PMID- 11007039
TI - Myogenin is a specific marker for rhabdomyosarcoma: an immunohistochemical study
in paraffin-embedded tissues.
AB - Myogenin belongs to a group of myogenic regulatory proteins whose expression
determines commitment and differentiation of primitive mesenchymal cells into
skeletal muscle. The expression of myogenin has been demonstrated to be extremely
specific for rhabdomyoblastic differentiation, which makes it a useful marker in
the differential diagnosis of rhabdomyosarcomas (RMS) from other malignant small
round cell tumors of childhood. Commercially available antibodies capable of
detecting myogenin in routinely processed formalin-fixed paraffin-embedded (FFPE)
tissue are now available. In this study, we evaluated myogenin expression using
the monoclonal myf-4 antibody (Novocastra Labs) on FFPE in a large number of
pediatric tumors in order to define the clinical utility of this marker. A total
of 119 tumors were studied. These included 48 alveolar RMS (ARMS), 20 embryonal
RMS (ERMS), one spindle cell RMS, 16 Ewing's sarcomas (ES), six nephroblastomas,
two ectomesenchymomas, seven precursor hematopoietic neoplasms, five olfactory
neuroblastomas, three neuroblastomas, six desmoplastic small round cell tumors,
and five rhabdoid tumors. Distinct nuclear staining for myogenin was noted in all
69 RMS. Notably, the number of positive tumor cells differed between the ARMS and
ERMS. In ARMS, the majority of tumor cells (75 to 100%) were positive, in
contrast to ERMS, in which the positivity ranged from rare + to 25% in all but
three tumors. Additionally, myogenin positivity was seen in two of two
ectomesenchymomas and in two nephroblastomas with myogenous differentiation. All
other tumors were clearly negative. Our results indicate that staining for
myogenin is an extremely reliable and specific marker for rhabdomyoblastic
differentiation. It gives consistent and easily interpretable results in
routinely fixed tissues.
PMID- 11007040
TI - Molecular abnormalities of p53, MDM2, and H-ras in synovial sarcoma.
AB - Forty-nine cases of synovial sarcoma were evaluated for mutation of the p53 gene,
amplification of the MDM2 gene and mutation of the H-ras gene, and for the
relation of these factors to overall survival and clinicopathologic parameters.
All investigations were carried out on formalin-fixed paraffin-embedded
materials. Furthermore, we evaluated the expression of p53 protein, MDM2, and
p21(WAF1/CIP1) immunohistochemically in these cases, together with an assessment
of proliferative activities using monoclonal antibody MIB-1. Nine of the 49 cases
(18.4%) had p53 gene alteration detected by polymerase chain reaction-single
strand conformation polymorphism (PCR-SSCP) and direct sequencing. Eleven cases
(24%) showed nuclear accumulation of p53 protein in more than 10% of the tumor
cells. Among them, only three cases contained gene mutations. There was no
correlation between p53 nuclear accumulation and p53 gene alteration. MDM2 gene
amplification, as shown by differential PCR, was observed in 19 out of 47 cases
(40%). Nineteen out of 49 cases (38.8%) showed immunoreactivity for MDM2. MDM2
gene amplification and the expression of MDM2 protein showed a significant
positive relationship (P = 0.0004). Moreover, MDM2 immunoreaction was
significantly correlated with nuclear accumulation of p53 protein (P = 0.023).
Positive immunoreaction for p21(WAF1/CIP1) was observed in 21 out of 48 cases
(43.8%). p21(WAF1/CIP1) expression was correlated with p53 protein expression. H
ras gene mutations were seen in only three cases (6.1%). All mutations were in
codon 12 (one GGC-to-AGC [Gly-to-Ser] mutation and two GGC-to-GAC [Gly-to-Ap]
mutations). The gene alteration of p53, MDM2, and H-ras did not affect the
patients' prognosis. Although the cases with positive immunoreaction for p53
tended to have a worse prognosis, the difference was not statistically
significant (P = 0.13). No correlation was observed between MIB-1 LI and the
immunohistochemical expression of p53, MDM2, and p21(WAF1/CIP1) or the mutation
status of p53 and H-ras. On the other hand, high MIB-1 LI (more than 10)
significantly correlated with poor prognosis (P < 0.0001). Our results suggest
that p53 gene mutation does not appear to be a major prognostic factor and H-ras
mutations are infrequent in synovial sarcoma.
PMID- 11007041
TI - Beta-catenin in soft tissue sarcomas: expression is related to proliferative
activity in high-grade sarcomas.
AB - Besides its role in cell adhesion, beta-catenin exerts a function as an
oncoprotein. The aim of this study was the characterization of its expression,
possible mutation, and the assessment of beta-catenin as a prognostic indicator
for soft tissue sarcomas. A total of 115 soft tissue sarcomas were analyzed using
immunohistochemistry, immunogold-electron microscopy, and DNA analysis.
Information from 56 patients was available for follow-up. A statistically
significant correlation was found between intracellular distribution of beta
catenin and the proliferative activity (MIB-1 expression) in high-grade sarcomas
(P = .0008). Beta-catenin was identified with intracytoplasmic and nuclear
accumulation, showing additional membranous staining in sarcomas with epithelioid
pattern. Ultrastructurally, a colocalization between beta-catenin and nuclear
heterochromatin was demonstrated. In 22 analyzed tumors, only one (yet
undescribed) mutation of the beta-catenin gene (C-A transversion) could be
detected. Prognostic validity of the cellular expression of beta-catenin,
however, was not proven. Apart from its membranous function as an effective
molecule for cell-adhesion in sarcomas with epithelioid pattern, beta-catenin may
act as an oncoprotein in sarcomas with intracytoplasmic and nuclear localization
with binding to nuclear DNA. A previously discussed stimulation of cell
proliferation caused by an increased beta-catenin level can also be postulated
for high-grade soft tissue sarcomas in correlation with the rate of
proliferation. Mutations of the beta-catenin gene are probably of lesser
importance for the accumulation of beta-catenin in soft tissue sarcomas.
PMID- 11007042
TI - p27kip1 expression distinguishes papillary hyperplasia in Graves' disease from
papillary thyroid carcinoma.
AB - In most cases, the histopathologic and cytologic distinction between Graves'
disease and papillary thyroid carcinoma is relatively easy, but on occasion
Graves' disease may simulate a thyroid papillary carcinoma. For example,
papillary fronds with fibrovascular cores may be present in both Graves' disease
and papillary carcinoma. p27kip1 (p27) is a cyclin-dependent kinase inhibitory
protein that has been shown to be an independent prognostic factor in a variety
of human tumors. Our previous studies of p27 expression in hyperplastic and
neoplastic endocrine lesions showed that the level of p27 was quite different in
these two conditions. To determine if this distinction could also be made between
Graves' disease and papillary carcinoma, we analyzed expression of p27 and other
cell cycle proteins in a series of cases of Graves' disease with papillary
hyperplasia and a series of papillary thyroid carcinomas. Formalin-fixed paraffin
embedded tissues from 61 randomly selected patients with thyroid disease,
including 29 cases of Graves' disease with papillary architectural features and
32 cases of papillary carcinoma, were analyzed for expression of p27, Ki-67, and
DNA topoisomerase II alpha (topo II alpha) by immunostaining. The distribution of
immunoreactivity was analyzed by quantifying the percentage of positive nuclei
that was expressed as the labeling index (LI) plus or minus the standard error of
the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 +/-
3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 +/- 2.5
(range, 12 to 70) (P < .0001). No significant differences in Ki-67 or topo II
alpha expression were identified between papillary hyperplasia in Graves' disease
and papillary carcinoma. These results indicate that p27 protein expression is
significantly higher in papillary hyperplasia of Graves' disease compared to
papillary carcinoma, which may be diagnostically useful in difficult cases.
PMID- 11007044
TI - Recommendations for the reporting of surgical specimens containing uterine
cervical neoplasms.
PMID- 11007043
TI - Increased density of interstitial mast cells in amyloid A renal amyloidosis.
AB - Renal interstitial fibrosis is the final common pathway leading to end-stage
renal disease in various nephropathies including renal amyloidosis. However, the
role of mast cells (MCs) in the fibrotic process of renal amyloidosis is not
fully understood. We compared the distribution of MCs in renal biopsies from 30
patients with AA type renal amyloidosis and 20 control cases. Immunoreactivity of
renal MCs to anti-tryptase and anti-chymase was studied. Interstitial
myofibroblasts were stained with anti-alpha-smooth muscle actin (alpha-SMA)
antibody, and inflammatory cells were identified by anti-CD45, -CD20, and -CD68
mAbs. Positively stained cells were counted, and the relative interstitial and
fractional areas of anti-alpha-SMA stained cells were measured. Anti-CD29 mAb was
used to detect beta1 integrin and anti-basic fibroblast growth factor (bFGF) mAb
for the growth factor on MCs. MCs were rarely found in control samples. In
contrast, samples showing amyloid deposition contained numerous tryptase-positive
(MCT) (940.17 +/- 5.4 versus 6.74 +/- 1.1/mm2) but fewer chymase-positive (MCTC)
cells (20.7 +/- 2.86 versus 1.7 +/- 0.76/mm2) in the renal interstitium. There
was a significant relationship between interstitial MCT and creatinine clearance
(r = -0.72), and between interstitial MCT and glomerular amyloid-index (GAI) (r =
0.723) and interstitial amyloid area (r = 0.824). Accumulation of MCs correlated
significantly with the number of T lymphocytes (MCT: r = 0.694). There was also a
significant relationship between mast cell (MC) number and the fractional area of
alpha-SMA positive interstitium (r = 0.733) and interstitial fibrotic area (r =
0.6). Double immunostaining demonstrated intracytoplasmic presence of beta1
integrin on 87% of MCT and correlated significantly with the interstitial amyloid
area (r = 0.818, P = .001) and T-cell number (r = 0.639, P = .002). bFGF was also
detected on 85.5% of MCTC correlating well with the interstitial alpha-SMA-area
(r = 0.789). Our results indicate that MCs constitute an integral part of the
overall inflammatory process and play a crucial role in interstitial fibrosis in
renal amyloidosis.
PMID- 11007045
TI - Recommendations for the reporting of resected esophageal carcinomas.
PMID- 11007046
TI - Recommendations for the reporting of specimens containing oral cavity and
oropharynx neoplasms.
PMID- 11007047
TI - Recommended reporting format for thyroid carcinoma.
PMID- 11007048
TI - Protocol for malignant and potentially malignant neoplasms of the testis and
paratestis.
PMID- 11007049
TI - The importance of documenting the appearance and status of breast implants at
time of explantation.
PMID- 11007050
TI - Acute clinical events in 299 homozygous sickle cell patients living in France.
French Study Group on Sickle Cell Disease.
AB - A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the
cohort of the French Study Group on sickle cell disease (SCD), was investigated
in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr)
of first generation immigrants from Western and Central Africa, the others
originated from the French West Indies (20.2%). We report the frequency of the
main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of
meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute
chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%)
developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy
two patients (58%) suffered from one or more painful sickle cell crises, while
the others (42.5%) never suffered from pain. The overall frequency of acute
anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic
sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr).
Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia
strongly reduced the risk of stroke (p <0.001) and increased that of painful
crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas
chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03).
Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27
patients (p < 0.02). The patients come from a population of unmixed immigrants in
whom the beta-globin gene haplotype strongly reflects the geographic origin and
identifies subgroups with a homogenous genetic background. Thus the observed
effects might result more from differences in as yet unidentified determinants in
the genetic background than from the direct linkage with differences in the beta
globin gene locus.
PMID- 11007051
TI - Pregnancy in essential thrombocythaemia: treatment and outcome of 17 pregnancies.
AB - OBJECTIVE: To evaluate treatment and outcome of 17 pregnancies in nine patients
with essential thrombocythaemia (ET) seen at our institution from 1988 to 1998.
METHODS: Treatment and outcome of 17 pregnancies in nine ET patients were
retrospectively analyzed. RESULTS: Seventeen pregnancies in nine patients with ET
resulted in 11 (65%) live births and ended in six (35%) spontaneous abortions.
Abortion could not be predicted from ET-associated complications before (p= 0.23)
or during (p = 0.39) pregnancy. Maternal complications occurred during six
pregnancies (35%): Three major bleedings in two patients with an acquired von
Willebrand disease and two minor bleedings in patients treated with low-dose
acetylsalicylic acid (ASA) were observed during pregnancy or at term; one patient
suffered from transient visual loss while pausing low-dose ASA. Platelet counts
prior to pregnancy were significantly higher as compared to the platelet nadir
observed during pregnancy (p = 0.0017). Postpartum clinical course was uneventful
in all patients. No specific treatment was given during 11 pregnancies. Six women
received low-dose ASA during pregnancy followed by low-molecular-weight heparin
until the end of the sixth week postpartum in five cases. This treatment was
correlated with a favourable outcome (live birth versus abortion) when compared
to no treatment (p=0.04). CONCLUSION: Pregnancy in ET can be complicated by first
trimester abortion and/or maternal haemorrhage. Our limited observation suggest a
positive impact of low-dose ASA during pregnancy followed by low-molecular-weight
heparin postpartum on pregnancy outcome in ET; nevertheless, confirmation by
prospective documentation is mandatory.
PMID- 11007052
TI - Megakaryocyte c-Mpl expression in chronic myeloproliferative disorders and the
myelodysplastic syndrome: immunoperoxidase staining patterns and clinical
correlates.
AB - The objectives of this study were to expand on recent observations that have
suggested decreased thrombopoietin receptor (c-Mpl) expression in megakaryocytes
of patients with polycythemia vera (PV) and agnogenic myeloid metaplasia (AMM).
We applied an immunoperoxidase method with anti-c-Mpl antibody to 55 bone marrow
sections from previously untreated patients with chronic myeloproliferative
disorder (CMPD) or myelodysplastic syndrome (MDS). These included 8 patients with
PV, 15 with AMM, 9 with essential thrombocythemia, 5 with chronic myelocytic
leukemia, 9 with the 5q-syndrome and 9 with MDS with fibrosis. The findings were
compared with those in four patients with reactive erythrocytosis (RE), six with
immune thrombocytopenic purpura (ITP) and five normal controls. Staining
intensity (SI) was moderate to strong both in normal controls and in patients
with RE or ITP. In contrast, SI was weak in variable proportions of the
megakaryocytes in every one of the aforementioned clonal myeloid disorders. The
staining pattern (SP) was relatively uniform in MDS and heterogeneous in CMPD.
Neither SI nor SP was significantly correlated with certain clinical or
laboratory parameters. We concluded that altered megakaryocyte c-Mpl expression
may be a nonspecific phenomenon in various subtypes of both CMPD and MDS.
However, the characteristic staining patterns may complement the morphological
distinction between clonal and reactive myeloproliferation.
PMID- 11007053
TI - Renal failure in multiple myeloma: reversibility and impact on the prognosis.
Nordic Myeloma Study Group.
AB - The purpose of the present study was to analyse the importance and prognostic
value of renal failure in multiple myeloma patients. The frequency and
reversibility of renal failure in 775 multiple myeloma patients diagnosed between
1984-86 and 1990-92 in the Nordic countries were studied. Renal failure, defined
as plasma creatinine > 130 micromol/l, was observed in 29% of the cases at the
time of diagnosis. During the first year after diagnosis 58% achieved
normalisation of p-creatinine, and this was achieved mainly during the first 3
months. Reversibility of renal failure was more frequently observed in patients
with moderate renal failure, hypercalcaemia and low Bence-Jones protein
excretion. In a multivariate analysis renal failure, high age, stage III disease
and hypercalcaemia were independent prognostic factors for survival. Patients who
needed dialysis had a poor prognosis, with a median survival of 3.5 months. A 12
months landmark analysis showed that reversibility of renal failure was a more
important prognostic factor than response to chemotherapy. It is concluded that
renal failure in multiple myeloma is reversible in about half the cases, and
reversibility of renal failure improves long-term survival.
PMID- 11007054
TI - Triple Philadelphia chromosomes with major-bcr rearrangement in hypotriploid
erythroleukaemia.
AB - The Philadelphia (Ph) chromosome is observed in approximately 1% of patients with
acute myeloblastic leukaemia (AML), especially subtypes M1 and M2 in the French
American-British classification. We describe here a cytogenetic and molecular
investigation of a rare case with Ph-positive AML M6 (erythroleukaemia). A 63-yr
old woman was diagnosed as having erythroleukaemia. Leukaemic cells were positive
for CD4 and CD7 as well as CD13, CD33, CD34 and HLA-DR. They were analyzed by G
banding, fluorescence in situ hybridization (FISH), Southern blot and reverse
transcriptase polymerase chain reaction analyses. The karyotypes at diagnosis
were as follows: 61, XX, -X, -1, -2, -3, -4, -5, -7, t(9;22)(q34;q11)x 2, -15,
16, -17, -18, + 19, +21, +22 [3]/61, idem, -22, +der(22)t(9;22) [36]. FISH with
BCR/ABL probes showed that 39% and 57% of interphase nuclei had double and triple
BCR/ABL fusion signals, respectively. Chromosome analysis in complete remission
showed a normal karyotype in all 20 metaphases, confirming the diagnosis as Ph
positive-acute leukaemia. FISH at relapse showed that 92% of interphase nuclei
had triple fusion signals. Rearrangement of major breakpoint cluster region (M
bcr) in the BCR gene and coexpression of p210-type (b2a2) and p190-type (e1a2)
BCR/ABL fusion transcripts due to alternative splicing were also detected. We
conclude that clonal evolution from double to triple Ph chromosomes may be
implicated in the disease progression. Considering other two reported cases, Ph
positive erythroleukaemia appears to be correlated with coexpression of myeloid/T
lymphoid markers and hyperdiploidy with double or triple Ph chromosomes, although
breakpoints in the BCR gene are heterogenous.
PMID- 11007055
TI - CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin,
prednisolone) regimen with granulocyte colony-stimulating factor (G-CSF) for
patients with aggressive non-Hodgkin's lymphoma: a pilot study. The Adult
Lymphoma Treatment Study Group (ALTSG).
AB - We conducted a multi-institutional collaborative study to examine the usefulness
and safety of third-generation chemotherapy CyclOBEAP (cyclophosphamide,
vincristine, bleomycin, etoposide, doxorubicin, prednisolone) combined with
granulocyte colony-stimulating factor (G-CSF) in the treatment of aggressive non
Hodgkin's lymphoma (NHL). Subjects included patients with aggressive NHL who were
60 yr of age or younger and had been diagnosed as having a low-intermediate, high
intermediate, or high risk using the International Prognostic Index (IPI). A
total of 24 patients were enrolled in the study between May 1997 and March 1998,
including 9 low-intermediate-risk cases, 13 high-intermediate-risk cases and 2
high-risk cases. Although all 24 patients were originally enrolled in the study,
one adult T-cell leukemia/lymphoma case was subsequently excluded. Thus, in the
end, 23 cases were evaluated. Evaluation of the efficacy of therapy revealed
complete remission in 20 patients (87%). Of these 20 patients, 8 were low
intermediate-risk cases (89%) and 12 were either high-intermediate- or high-risk
cases (86%). Partial remission was achieved in 2 patients (8.7%). The 2-yr
survival rate was 91.3%, and the 2-yr disease-free survival rate was 81.8%. Grade
3 or higher adverse reactions were granulocytopenia (87%), thrombocytopenia
(17.4%) and liver dysfunction (4.3%). CyclOBEAP therapy has been associated with
a high remission rate for aggressive NHL. When combined with G-CSF, a high
relative dose intensity was maintained for each drug administered (0.94-0.97).
Furthermore, although the observation period was short, both the survival rate
and disease-free survival rate were good. Hence, we concluded that there were no
problems associated with the procedure in terms of safety.
PMID- 11007056
TI - Elevated serum levels of soluble CD44 variant 6 are correlated with shorter
survival in aggressive non-Hodgkin's lymphoma.
AB - A variant form of CD44 that has additional amino acids in the common protein
backbone (CD44-v6) seems to play a role in the metastasis of malignancies. We
measured soluble CD44-v6 (sCD44-v6) by ELISA in 201 patients with malignant
lymphoma. The sCD44-v6 level was significantly elevated in patients with non
Hodgkin's lymphoma (NHL) (n = 184). The sCD44-v6 level was correlated
significantly with the standard sCD44 and soluble interleukin-2 receptor levels,
but only weakly with serum lactate dehydrogenase (LDH). In 149 patients with
aggressive NHL, the sCD44-v6 level was elevated in the subgroups with a high LDH
level, stage III/IV disease, T-cell lymphoma, and high-intermediate or high risk
group as identified by the International Prognostic Index (IPI). When the sCD44
v6 level was > or = 800 ng/ml the overall survival rate was significantly
decreased (p = 0.0001). In the low + low-intermediate risk group (IPI) both
overall survival rates (log-rank p = 0.0005, Wilcoxon p =0.002) were
significantly decreased when the sCD44-v6 level was > or = 800 ng/ml. In
multivariate analysis, sCD44-v6 was shown to be independent of the five
prognostic factors in the IPI (age, performance status, number of extranodal
sites, Ann Arbor stage and LDH level), so it may be useful for predicting the
outcome of aggressive NHL.
PMID- 11007057
TI - Molecular and cytogenetic remission in a case of subtype M4E acute myelogenous
leukemia with minimal monochemotherapy: high sensitivity or spontaneous
remission?
AB - Complete remission was observed in an adult patient with acute myelogenous
leukemia after minimal monochemotherapy. Remission occurred after a severe
febrile pneumonia and was accompanied by cytogenetic and molecular remission. The
hypothesis of spontaneous remission was raised, even if a high sensitivity to low
dose cytostatics cannot be excluded. Such spontaneous complete remissions, often
associated with bacterial infections and blood transfusions, are extremely rare,
and are usually of short duration. Previous cases are summarized, and the role of
etiologic factors is discussed.
PMID- 11007058
TI - Interferon alpha is an effective therapy for congenital dyserythropoietic anaemia
type I.
AB - The efficacy of interferon-alpha (IFN) was reported in three patients with
congenital dyserythropoietic anaemia (CDA) type I. We describe two additional
cases treated with IFN, which normalized the haemoglobin level in both patients
with a dramatic decrease in the size of the spleen in one. Haemoglobin remained
stable more than 6 months after discontinuation of treatment. IFN induced more
than 50% decrease in the number of BFU-E in both patients' bone marrow cultures,
suggesting an indirect effect of IFN on erythropoiesis in vivo. We conclude that
a trial of IFN therapy should be considered in patients with CDA type I.
PMID- 11007059
TI - The pathogenetic mechanism of myeloid malignancies associated with deletions of
the long arm of chromosome 20 can not be explained by a "one hit" model. An acute
myeloid leukemia patient who developed with 20q- clone during complete remission
for 9 years.
PMID- 11007060
TI - Chronopharmaceutical drug delivery from a pulsatile capsule device based on
programmable erosion.
AB - We report the development of a chronopharmaceutical capsule drug delivery system
capable of releasing drug after pre-determined time delays. The drug formulation
is sealed inside the insoluble capsule body by an erodible tablet (ET). The
release time is determined by ET erosion rate and increases as the content of an
insoluble excipient (dibasic calcium phosphate) and of gel-forming excipient
(hydroxypropylmethylcellulose; HPMC) increases. The time-delayed release of a
model drug (propranolol HCI) was investigated by dissolution testing (USP XXIII
paddle method). Both composition and weight of ET influence the time of drug
release. Moreover it was found that drug release was controlled by the quantity
of HPMC, irrespective of lactose content within the tablet weight range 80-160
mg, when above a threshold concentration of 20% HPMC. Programmable pulsatile
release has been achieved from a capsule device over a 2-12-h period, consistent
with the demands of chronotherapeutic drug delivery. The time of drug release can
be controlled by manipulation of tablet formulation.
PMID- 11007061
TI - Improvement of subcutaneous bioavailability of insulin by sulphobutyl ether beta
cyclodextrin in rats.
AB - The objective of this study was to examine and compare how hydrophilic beta
cyclodextrin derivatives (beta-CyDs) improve the bioavailability of insulin
following subcutaneous injection of insulin solution in rats. When insulin
solutions in the absence of beta-CyDs were injected into the dorsal subcutaneous
tissues of rats, the absolute bioavailability of insulin calculated from plasma
immunoreactive insulin (IRI) levels was approximately 50%. When maltosyl-beta
cyclodextrin was added to the solutions, there was no change in the plasma IRI
levels and hypoglycaemia compared with those of the insulin-alone solution.
Dimethyl-beta-cyclodextrin decreased the bioavailability of insulin, although it
increased the maximal concentration of IRI in plasma and the capillary
permeability of the fluorescein isothiocyanatedextran 40, a non-degraded
permeation marker. When insulin solutions containing sulphobutyl ether-beta
cyclodextrin with a degree of substitution of the sulphobutyl group of 3.9 (SBE4
beta-CyD) were injected, the IRI level rapidly increased and maintained higher
IRI levels for at least 8 h. The bioavailability of the insulin/SBE4-beta-CyD
system was about twice that of insulin alone and approached 96%. The enhancing
effects of SBE4-beta-CyD may be in part due to the inhibitory effects of SBE4
beta-CyDs on the enzymatic degradation and/or the adsorption of insulin onto the
subcutaneous tissue at the injection site, although this does not apparently
facilitate capillary permeability. These results suggest that SBE4-beta-CyD in
aqueous insulin injection for subcutaneous administration is useful for improving
the bioavailability and the hence the pharmacological effects of insulin.
PMID- 11007062
TI - Ion-pair formation as a strategy to enhance topical delivery of salicylic acid.
AB - An in-vitro study was carried out to determine the possibility of improving the
efficiency of transdermal delivery of salicylate through human epidermis by ion
pair formers (alkylamines and quaternary ammonium ions). Further, the
relationship between the physicochemical properties of the counter-ions and
salicylate flux was examined. It was found that flux can be related to the
conductivity associated with the penetrant solution, molecular size of the
counter-ion and lipophilicity expressed as either octanol/water partition
coefficient of the ion pairs or the carbon chain-length of the counter-ions.
Equations have been developed to predict salicylate flux from these
physicochemical parameters.
PMID- 11007064
TI - An investigation into the low temperature thermal behaviour of vitamin E
preparation USP using differential scanning calorimetry and low frequency
dielectric analysis.
AB - The thermal and dielectric responses of Vitamin E Preparation USP have been
examined to further understand the melting and solidification of this material. A
TA Instruments 2920 Differential Scanning Calorimeter was used to examine the
thermal response of the sample at a range of scanning speeds. Isothermal
dielectric studies were performed using a Novocontrol Dielectric Spectrometer
over a range of temperatures down to -70 degrees C and a frequency range of 10(6)
10(-2) Hz. The differential scanning calorimetry (DSC) studies showed an
anomalous response whereby at slow heating rates (2 degrees C min(-1)) a small
exotherm followed immediately by an endotherm was observed. This response was
considerably diminished in magnitude at higher rates (5 degrees C min(-1)) and
was not observed at the fastest heating rate of 10 degrees C min(-1). No thermal
events were seen on cooling the sample to -60 degrees C. It was suggested that
the material formed a glass on cooling, with a predicted transition temperature
of approximately -100 degrees C. Further studies using a liquid nitrogen cooling
system indicated that the system did indeed exhibit a glass transition, albeit at
a higher temperature than predicted (ca -63 degrees C). Low frequency dielectric
analysis showed a clear relaxation peak in the loss component, from which the
relaxation time could be calculated using the Havriliak-Negami model. The
relationship between the relaxation time and the temperature was studied and was
found to follow the Vogel-Tammann-Fulcher (VTF) modification of the Arrhenius
equation. It is therefore concluded that Vitamin E Preparation USP is a glass
forming material that exhibits kinetically-hindered recrystallisation and melting
behaviour. The study has also indicated that DSC and low frequency dielectric
analysis may be powerful complementary tools in the study of the low temperature
behaviour of pharmaceuticals.
PMID- 11007063
TI - Effect of ion pairing with alkylamines on the in-vitro dermal penetration and
local tissue disposition of salicylates.
AB - Hydrophilic ionic drugs can be rendered lipophilic by ion-pair formation with
hydrophobic counter-ions. This study examines the value of forming ion pairs
between anionic salicylate and a series of amines as model cationic counter-ions
to facilitate topical delivery and skin penetration. The in-vitro translocation
of salicylate ions from a nonaqueous vehicle through human epidermis was
estimated in the presence or absence of amines. The distribution into, and
accumulation of the salicylate ion in various tissues following topical
application to anaesthetised rats were also investigated. Although the epidermal
permeation constants of the salicylate-amine ion pairs were lower than that of
salicylate itself (enhancement ratios: 0.74-0.87), salicylate retention and
localisation in the underlying rat tissues increased in the presence of some of
the counter-ions studied. Salicylate concentrations (microg (g tissue)(-1)) in
the dermis were 877.2+/-78.6 for salicylate alone and 1098+/-121.9-2586+/-332.5
for salicylate-amine ion pairs. The levels of salicylate in tissues up to the top
muscle layer were 1.2-3.7-fold higher in the presence of the counter-ions. It is
concluded that, although amine counter-ions have the ability to influence the
penetration of salicylate, in-vitro permeability studies do not reflect the in
vivo increases in tissue concentrations resulting from probable changes in
systemic clearance.
PMID- 11007065
TI - Solid dispersion of hydroxypropyl beta-cyclodextrin and ketorolac: enhancement of
in-vitro dissolution rates, improvement in anti-inflammatory activity and
reduction in ulcerogenicity in rats.
AB - Ketorolac, is a non-steroidal anti-inflammatory drug, with strong analgesic
activity. It is practically insoluble in water and has been implicated in causing
gastrointestinal ulceration. This study describes the formulation of solid
dispersions of ketorolac using hydroxypropyl beta-cyclodextrin (HPbeta-CyD) and
beta-cyclodextin (beta-CyD) as carriers, to improve the aqueous solubility of the
drug, thus enhancing its bioavailability. Also, reduction in ulcerogenicity was
anticipated. Differential scanning calorimetry and X-ray diffraction studies
indicated loss of crystalline nature of the drug, in the dispersions prepared
with HPbeta-CyD. NMR studies revealed a strong interaction between drug and
HPbeta-CyD. Solid dispersions of drug with beta-CyD retained the crystalline
nature of the drug. All the solid dispersions showed a remarkable improvement in
the rate and extent of dissolution of ketorolac. The kneaded dispersion with
HPbeta-CyD prepared using a 1:1 alcohol-water mixture showed promise in reducing
the ulcer-inducing effect of ketorolac in rats. Oral administration of this
dispersion was found to inhibit carrageenan-induced paw oedema in rats to a
significantly greater extent compared with ketorolac or its trometamol salt.
Though beta-CyD as a carrier for ketorolac gave faster release of the poorly
soluble drug, HPbeta-CyD proved to be superior to beta-CyD, as a carrier in the
kneaded dispersion prepared using 1:1 alcohol-water mixture. These results
suggest that solid dispersions of ketorolac with HPbeta-CyD aid in faster
dissolution and better bioavailability of the drug. The higher solubility of the
drug in the presence of HPbeta-CyD also reduces local gastrointestinal side
effects of the drug.
PMID- 11007066
TI - Estimation of oral bioavailability in the rat by the accelerated infusion
technique.
PMID- 11007067
TI - Simultaneous determination of unbound cefoperazone in rat blood and brain using
microdialysis.
AB - A sensitive microbore HPLC method was developed for the simultaneous
determination of unbound cefoperazone in rat blood and brain using microdialysis.
Two microdialysis probes were inserted into the jugular vein/right atrium and
brain striatum of Sprague-Dawley rats. Cefoperazone (50 mgkg(-1), i.v.) was then
administered via the femoral vein. Blood and brain dialysates were collected and
eluted with a mobile phase containing methanol-100 mM monosodium phosphoric acid
(30:70, v/v, pH 5.5). The wavelength of the UV detector was set at 254 nm. The
detection limit of cefoperazone was 20 ng mL(-1). Isocratic separation of
cefoperazone was achieved within 10 min. The intra- and inter-assay accuracy and
precision of the analyses were < or =10% in the range of 0.05-10 microg mL(-1).
The ratio of the area under the concentration curve of cefoperazone in rat brain
and blood was estimated to be about 7-8%. It is concluded that cefoperazone is
capable of penetrating the blood-brain barrier.
PMID- 11007068
TI - Ventricular function and cardiac hypertrophy after coronary thrombolysis with
tissue-type plasminogen activator (t-PA) in dogs with coronary artery thrombi.
AB - Subacute prognosis of cardiac function after thrombolysis with a modified tissue
type plasminogen activator (t-PA) YM866 was determined in dogs with coronary
artery thromboses induced by injection of a thrombin, fibrinogen and autogenous
blood mixture. The left ventricular ejection fraction (LVEF) decreased 30 min
after occlusion and had not improved 1 week later. Examination after sacrifice
revealed myocardial infarction as well as increases in both the left ventricular
myocardial area and heart mass. Occluded coronary arteries reperfused by YM866
(0.1 mg kg(-1) i.v.) treatment 30 min after occlusion, by contrast, had improved
LVEF and inhibited myocardial infarction development. In addition, the left
ventricular myocardial area and heart mass were significantly reduced compared
with the vehicle control group 1 week after administration. Although occluded
coronary arteries reperfused by YM866 (0.1 mg kg(-1) i.v.) treatment 3 h after
occlusion did not show an improvement in the LVEF or inhibition of myocardial
infarction development, the left ventricular myocardial area and heart mass
decreased significantly compared with the vehicle control group 1 week after
administration. In conclusion, early reperfusion by t-PA treatment 30 min after
occlusion improved the ventricular function and cardiac hypertrophy, whereas late
reperfusion by t-PA treatment 3 h after occlusion did not improve the ventricular
function but did inhibit hypertrophy in dogs with coronary artery thrombi.
PMID- 11007069
TI - Tiospirone and the reinforcing effects of cocaine in the conditioned place
preference paradigm in rats.
AB - Tiospirone (TSP) is an atypical antipsychotic drug. It has 5HT-2 antagonistic
properties as well as affinity for D2, 5HT-1a, 5HT-6 and sigma receptors.
Behavioural studies in our laboratory, which used a 24h free access to food and
fluids paradigm, showed a decreased alcohol and increased food intake after twice
daily administration of TSP; the maximal effect was obtained at a dose of 0.48 mg
kg(-1). This study used the conditioned place preference paradigm to determine
the effect of TSP on the reinforcing properties of cocaine. Intraperitoneal
administration of 5.0 mg kg(-1) cocaine, but not saline, increased the time rats
spent in the drug-paired compartment of a three-compartment shuttle box by
104.9%. Two doses of TSP, 0.143 and 0.48 mgkg(-1), were tested subcutaneously 60
min before saline or cocaine administration during the conditioning phase only. A
dose-response effect was observed with a significant reduction in the time rats
spent in the cocaine-paired compartment on the drug-free test day produced by the
dose of 0.48 mg kg(-1) (an increase of only 38.1% when post-conditioned times
were compared with preconditioned times). These findings suggest that TSP reduces
the reinforcing properties of cocaine exhibited in the conditioned place
preference paradigm.
PMID- 11007070
TI - The effects of potassium channel blockers on progesterone-induced suppression of
rat portal vein contractility.
AB - The suppression of contractility of rat portal vein caused by progesterone
appears to be due to the potassium (K+) channel opening effect of this hormone.
The identity of the specific K+ channels involved has been investigated using a
variety of K+ channel blockers. Incubation with 100 nM iberiotoxin antagonised
the progesterone-induced inhibition of spontaneous and 20 mM K+-induced phasic
activity of the portal vein such that the contractions resembled those of the non
progesterone, non-iberiotoxin control tissues treated with the corresponding
solvent vehicles. Incubation with barium chloride (20 and 100 microM), 4
aminopyridine (1 mM), tetraethylammonium chloride (1 mM), glibenclamide (1
microM) or apamin (1 microM) did not, however, have the same antagonistic effect.
These results suggest that progesterone's selective suppression of rat portal
vein contractility is mediated by the opening of BKCa channels.
PMID- 11007071
TI - Effect of Aegle marmelos on biotransformation enzyme systems and protection
against free-radical-mediated damage in mice.
AB - The effect of hydroalcoholic (80% ethanol, 20% water) extract of leaves of Aegle
marmelos was examined on carcinogen-metabolizing phase-I and phase-II enzymes,
antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid
peroxidation, using two doses of dried extract (50 and 100 mg kg(-1) daily for 14
days), in the liver of mice. The modulatory effect of the extract was also
examined on extrahepatic organs (lung, kidney and fore-stomach) for effects on
the activity of glutathione S-transferase, DT-diaphorase, superoxide dismutase
and catalase. Extract treatment significantly increased the basal levels of acid
soluble sulphydryl (-SH) content, cytochrome P450, NADPH-cytochrome P450
reductase, cytochrome b5, NADH-cytochrome b5 reductase, glutathione S
transferase, DT-diaphorase, superoxide dismutase, catalase, glutathione
peroxidase and glutathione reductase in the liver. Aegle acted as a bifunctional
inducer since it induced both phase-I and phase-II enzyme systems. Both doses
significantly decreased the activity of lactate dehydrogenase and formation of
malondialdehyde in liver, suggesting a role in cytoprotection as well as
protection against pro-oxidant-induced membrane damage. Butylated hydroxyanisole
(positive control) induced almost all the antioxidative parameters measured in
this study. The extract was effective in inducing glutathione S-transferase, DT
diaphorase, superoxide dismutase and catalase in lung, glutathione S-transferase,
DT-diaphorase and superoxide dismutase in fore-stomach, and DT-diaphorase and
superoxide dismutase in lung. These significant changes in the levels of drug
metabolizing enzymes and antioxidative profiles are strongly indicative of the
chemopreventive potential of this plant, especially against chemical
carcinogenesis.
PMID- 11007072
TI - The effect of acute ethanol exposure on the chronotropic and inotropic function
of the rat right atrium.
AB - Consumption of ethanol (CH2CH3OH), both acutely and chronically, is known to
affect cardiac function and may alter the autonomic control of the heart. This
study investigated the effects of two modes of acute exposure to ethanol on the
chronotropy and inotropy of the rat right atrium with emphasis on alterations in
the adrenergic responses. Atria from rats infused with an anesthetizing level of
ethanol for 21 h showed a tendency for a greater increase of the unstimulated
beating rate with isoproterenol (ISO), while both unstimulated inotropy and the
inotropic response to ISO were significantly decreased compared with the control.
Right atria in the presence of ethanol in-vitro demonstrated decreased basal
active tension development and decreased inotropic responses to ISO. No
alteration of the chronotropic response to ISO was evident with any concentration
of ethanol. These results demonstrate both an immediate as well as a persistent
effect of ethanol on right atrial chronotropy and inotropy. Alterations in the G
stimulatory subunit of the adenylate cyclase system and alterations in
myofilament binding of Ca2+ are consistent with these observed ethanol effects.
PMID- 11007073
TI - Uptake and dispersion of metformin in the isolated perfused rat liver.
AB - Although metformin is a widely used oral antihyperglycaemic, the exact mechanisms
of its cellular uptake and action remain obscure. In this study the hepatic
extraction and disposition kinetics of metformin were investigated by use of an
isolated in-situ rat liver preparation. The liver was perfused in single-pass
mode with protein-free Krebs bicarbonate medium at a flow rate of 20 mL min(-1).
During constant infusion with 1 mg L(-1) metformin hydrochloride the hepatic
uptake of metformin approached equilibrium within 10 min. The steady-state
availability, F, determined from the ratio of outflow concentration to input
concentration, was 0.99+/-0.02 (mean +/- s.d., n = 4). The outflow profile of
metformin resulting from a bolus injection of 25 microg into the portal vein, had
a sharp peak then a slower declining terminal phase. The mean transit time (MTT;
49.5+/-14.5, n = 6) and normalized variance (CV2; 4.13+/-0.05) of the hepatic
transit times of metformin were estimated by numerical integration from the
statistical moments of the outflow data. The volume of distribution of metformin
in the liver (1.58+/-0.28 mL (g liver)(-1)) was estimated from its MTT. The
volume of distribution is greater than the water space of liver, indicating that
metformin enters the hepatic aqueous space and becomes distributed among cellular
components. The magnitude of CV2 for metformin is greater than for the vascular
marker sucrose, suggesting that distribution of metformin into hepatic tissue is
not instantaneous. In conclusion, hepatic uptake of metformin is rate-limited by
a permeability barrier. Although metformin is accumulated in the liver, the organ
does not extract it.
PMID- 11007074
TI - Does dihydrohonokiol, a potent anxiolytic compound, result in the development of
benzodiazepine-like side effects?
AB - The aims of this study were to assess whether dihydrohonokiol, 3'-(2-propenyl)-5
propyl-(1,1'-biphenyl)-2,4'-diol (DHH-B), a potent anxiolytic compound, developed
benzodiazepine-like side effects. A 1 mg kg(-1) dose of diazepam, almost
equivalent to the minimum dose for the anxiolytic effect, disrupted the traction
performance, potentiated hexobarbital-induced sleeping and impaired learning and
memory performance. DHH-B, even at a dose of 1 mg kg(-1) (i.e. five times higher
than the minimum dose for significant anxiolytic effect) neither developed
diazepam-like side effects nor enhanced the side effects of diazepam. Rather, the
potentiation by diazepam of hexobarbital-induced sleeping was reduced by 1 mg kg(
1) DHH-B. Furthermore, mice treated with 10 daily administrations of 1 and 5 mg
kg(-1) diazepam, but not 0.2-5 mg kg(-1) DHH-B, showed precipitated withdrawal
symptoms characterized by hyper-reactivity, tremor and tail-flick reaction when
they were challenged with flumazenil (10 mg kg(-1) i.p.). These results suggest
that, unlike the benzodiazepine anxiolytic diazepam, DHH-B is less likely to
induce motor dysfunction, central depression, amnesia or physical dependence at
the effective dose required for the anxiolytic effect.
PMID- 11007076
TI - Radish extract stimulates motility of the intestine via the muscarinic receptors.
AB - The effects of radish (Brassica oleraceae, Cruciferae) on gastrointestinal
motility were examined using rat intestinal segments with myenteric plexus in
vitro and measuring the intestinal transit of charcoal in-vivo. Radish extract
(10 microg mL(-1) to 2 mg mL(-1)) caused a dose-dependent increase in
contractions of the duodenum, jejunum and ileum, and 1 mg mL(-1) was the maximum
effective dose. The largest contraction by the extract was found in ileal
segments. The extract-induced (0.5 mg mL(-1)) ileal contraction was remarkably
inhibited by pretreatment of segments with atropine (10(-7) M) for 10 min, but
not by hexamethonium (0.5 mM). Moreover, antagonists of the muscarinic receptor
reduced the radish-induced ileal contraction by a different ratio. The rank order
of inhibitory effects was 4-diphenylacetoxy-N-methyl-(2-chloroethyl)-piperidine
methiodide (90.5% of control) > tropicamide (67.4%) > pirenzepine (42.8%) >
methoctramine (16.7%). Oral administration of radish extract (300-500 mg kg(-1)
body weight) to mice remarkably improved the intestinal transit of charcoal, and
this was significantly attenuated by co-administration of atropine (50 mg kg(
1)). Taken together, these results suggest that radish extract stimulates
gastrointestinal motility through activation of muscarinic pathways.
PMID- 11007075
TI - Interaction of drugs and Chinese herbs: pharmacokinetic changes of tolbutamide
and diazepam caused by extract of Angelica dahurica.
AB - The inhibitory effects of Angelica dahurica root extract on rat liver microsomal
cytochrome P450 and drug-drug interactions were studied. The 2alpha- and 16alpha
hydroxylase activity of testosterone were most strongly inhibited, with 17.2% and
28-5% of their activity remaining, respectively, after oral administration of A.
dahurica extract at a 1 g kg(-1) dose. 6beta-Hydroxylase activity was also
inhibited, with 70% of its activity remaining, under the same conditions. In
addition, treatment with the extract inhibited the metabolism of tolbutamide,
nifedipine and bufuralol. These results showed that the extract inhibited the
various isoforms of cytochrome P450 such as CYP2C, CYP3A and CYP2D1. The A.
dahurica extract delayed elimination of tolbutamide after intravenous
administration at a 10 mg kg(-1) dose to rats. Thus, the extract altered the
liver intrinsic clearance. It had little effect, however, on the pharmacokinetic
parameters of diazepam after intravenous administration at 10 mg kg(-1). Since
diazepam showed high clearance, it underwent hepatic blood flow rate-limited
metabolism. Therefore, the change of intrinsic clearance had little effect on
hepatic clearance. However, the Cmax value after oral administration of diazepam
with extract treatment was four times that with non-treatment. It was suggested
that the first-pass effect was changed markedly by the extract. High-dose (1 g
kg(-1)), but not low dose (0.3 g kg(-1)), administration of A. dahurica extract
increased significantly the duration of rotarod disruption following intravenous
administration of diazepam at 5 mg kg(-1). It was concluded that administration
of A. dahurica extract has the potential to interfere with the metabolism, by
liver cytochrome P450, of other drugs.
PMID- 11007077
TI - Induction of apoptosis in human leukaemic cell lines K562, HL60 and U937 by
diethylhexylphthalate isolated from Aloe vera Linne.
AB - We investigated the effect of diethylhexylphthalate (DEHP) from Aloe vera Linne
on the apoptosis of human leukaemic cell lines K562, HL60 and U937 to examine its
pharmacological activity. At a level of 10 microg mL(-1) DEHP a significant anti
leukaemic effect was observed for all three cell lines, as measured by clonogenic
assay. After treatment with 10 microg mL(-1) DEHP for 4 h, agarose gel
electrophoresis and flow cytometric analysis confirmed the occurrence of
apoptosis. These results indicate that DEHP isolated from Aloe vera Linne has a
potent antileukaemic effect, and thus represents a new type of pharmacological
activity with respect to human leukaemic cells.
PMID- 11007079
TI - Prevention of accidental childhood strangulation. A clinical study.
AB - Accidental strangulation is a preventable problem, and there is limited
scientific understanding of its mechanism in children. If the amount of external
pressure that occludes the airway can be determined, design changes may be made
to allow for production of household objects that would break apart at safe
pressure levels. A force gauge was applied to the suprahyoid region in 90
children under standardized anesthesia. Three blinded observers performed the
study. The anesthesiologist maintained the airway and used a stethoscope to
auscultate for breath sounds and monitor the CO2 curves to evaluate obstruction.
The recorder noted the numbers from the gauge. A single observer applied the
force gauge. Age was the most significant variable in occluding the airway.
Obstruction appears to occur at the level of the larynx. Increased knowledge
regarding the external pressure required for airway occlusion would allow for the
design and manufacture of products with a reduced potential for accidental
strangulation.
PMID- 11007078
TI - Experience with percutaneous dilational tracheostomy.
AB - Percutaneous dilational tracheostomy (PDT) has gained popularity among critical
care specialists in the past 10 years. The initial studies in our specialty
resulted in essentially banning the procedure as a dangerous substitute for
standard operative tracheostomy. Despite this action, more than 1,100 cases of
percutaneous tracheostomy have been reported with details on complications. We
reviewed all published data and studied 311 patients of our own. A prospective
study was performed in 3 groups of patients: 1) 50 patients scheduled for PDT
performed in the operating room by a head and neck surgeon (group 1); 2) 50
patients who underwent standard operative tracheostomy performed by the same
surgeon (group 2); and 3) 211 patients who underwent bedside PDT by critical care
physicians (group 3). The intraoperative complication rates were 0% in group 1,
2% in group 2, and 4% in group 3; the postoperative complication rates were 13%,
4%, and 12%, respectively. There were 2 deaths in group 3, and none in groups 1
or 2. The statistically significant differences among the groups were the
superiority of group I over group 3 in intraoperative complications, as well as
the lower postoperative complication rate of the standard tracheostomy group.
These results show that PDT can be performed with acceptable morbidity rates in
relation to published complication rates of standard tracheostomy, but it has no
advantage over standard tracheostomy with respect to postoperative morbidity.
When they are performed by a head and neck surgeon, the morbidity associated with
both standard and percutaneous tracheostomies can be reduced.
PMID- 11007080
TI - Dilatational versus standard tracheostomy: a meta-analysis.
AB - The advent of percutaneous dilatational tracheostomy (PDT) was initially viewed
by otolaryngologists with great skepticism. The purpose of this study was to
compare the complications of PDT with those of standard tracheostomy (ST) by a
meta-analysis of randomized studies. We found that ST had a fivefold higher rate
of complications than did PDT, and these complications were often more severe. We
conclude that PDT is a safer procedure for elective tracheostomy in carefully
selected patients, ie, those with normal-sized necks.
PMID- 11007081
TI - Perioperative airway complications following pharyngeal flap palatoplasty.
AB - This study was performed to determine the incidence and types of perioperative
airway complications after pharyngeal flap palatoplasty. We conducted a
retrospective chart review of 88 patients who underwent correction of
velopharyngeal insufficiency between April 30, 1983, and April 30, 1997, in a
tertiary care hospital. Some degree of airway obstruction developed in 7
patients. One child developed laryngobronchospasm and required immediate
endotracheal intubation. He was successfully extubated without sequelae. Another
patient developed severe obstructive sleep apnea and required flap revision. A
third patient was found asystolic and apneic. She was immediately intubated;
however, she subsequently died. Two patients aspirated blood, presumably
resulting in pneumonia. They were managed with parenteral antibiotics. Another
child developed worsening sleep apnea and required flap revision. One patient
developed nasal obstruction that resolved with time. Airway compromise in
patients who undergo pharyngeal flap palatoplasty can be a potentially fatal
complication. Careful surveillance should be maintained over patients with
underlying neurologic, craniofacial, or cardiopulmonary disorders.
PMID- 11007082
TI - Tracheobronchial extension of recurrent respiratory papillomatosis.
AB - Endobronchial and pulmonary dissemination reportedly occurs in 5% of patients
with laryngeal papillomatosis. It is more frequently observed in the juvenile
form, and carries significant implications for treatment. In this study, we
review our experiences with pulmonary and endobronchial extension of laryngeal
papillomatosis. The records of the 52 patients with laryngeal papillomas treated
at our institution since 1980 were reviewed. Twenty-nine percent of the patients
(N = 15) developed tracheobronchial extension; 7% (N = 4) demonstrated pulmonary
involvement. The birth history, race, sex, age at onset of symptoms, presenting
symptoms, site and type of papillomas, surgical procedures, other methods of
treatment, complications, and mortality data were analyzed. Eighty percent of the
patients with tracheobronchial involvement were born to mothers with a positive
history of vaginal condylomas. Pulmonary changes in 4 patients were observed on
either chest radiographs or computed tomography and were manifested as multiple
parenchymal nodules in 3 of the 4 patients. Pneumatoceles, cavitary empyema, and
multiple recurrent pneumonias were the predominant complications of pulmonary
involvement. Of the 15 patients with tracheobronchial extension, 80% (N = 12)
required tracheotomy before their presentation to us. The number of multiple
surgical procedures performed to remove papillomas ranged from 7 procedures in 1
patient with a solitary tracheobronchial lesion to more than 100 procedures in 2
patients with diffuse bronchopulmonary papillomatosis. As our study shows,
tracheobronchial involvement continues to complicate surgical treatment in this
challenging disease process.
PMID- 11007083
TI - Outcomes assessment following treatment of spasmodic dysphonia with botulinum
toxin.
AB - Spasmodic dysphonia (SD), a disabling focal dystonia involving the laryngeal
musculature, is most commonly treated by the intramuscular injection of botulinum
toxin (BTX). Although the treatment is well tolerated and generally produces
clinical voice improvement, it has never been statistically shown to alter the
patient's perception of voice quality or general health. Declining resources for
medical care mandate that treatment outcomes be documented. A prospective
analysis of the effects of BTX on the patient's perception of voice and general
health was undertaken. The Voice Handicap Index (VHI) and Short Form 36 (SF-36)
surveys were administered to patients before treatment and 1 month after.
Pretreatment and posttreatment scores were analyzed with a Student's t-test. On
the VHI, improvements in the patients' perception of their functional, physical,
and emotional voice handicap reached statistical significance (p < or = .0005).
On the SF-36, patients had statistically significant improvements in mental
health (p < or = .03) and social functioning (p < or = .04). Treatment of SD with
BTX significantly lessened the patients' perception of dysphonia. In addition, it
improved their social functioning and their perception of their mental health.
These outcome measures justify the continued treatment of SD with BTX.
PMID- 11007084
TI - Acoustic, aerodynamic, and videostroboscopic features of bilateral vocal fold
lesions.
AB - Successful treatment of bilateral vocal fold lesions depends on the accuracy of
the diagnosis. For example, the preferred treatment for vocal fold nodules is
voice therapy: in contrast. treatment for a unilateral vocal fold lesion with a
contralateral reactive vocal fold lesion (UVFL/RL) usually involves phonosurgery
and voice therapy. Differentiation between vocal fold nodules and a UVFL/ RL is
often challenging. The purpose of this study was to facilitate diagnostic
accuracy and improve treatment for patients with bilateral vocal fold lesions by
attempting to identify distinct features of patients with either vocal fold
nodules or a UVFL/RL with acoustic, aerodynamic, stroboscopic, and patient self
perception measures. The objective voice analysis, Voice Handicap Index, and
laryngovideostroboscopic examinations of 85 patients with bilateral vocal fold
lesions were reviewed. The results indicated that the patients with a UVFL/RL
presented a diagnostic profile that was significantly different from that of
patients with vocal fold nodules. Statistically significant differences were
found for 1) symmetry of vocal fold vibration, 2) amplitude perturbations, 3)
estimated subglottic pressure, and 4) Voice Handicap Index. These results suggest
that a composite assessment of acoustic, aerodynamic, and videostroboscopic
phonatory features facilitates differentiation between patients with vocal fold
nodules and those with a UVFL/RL. The improved diagnostic accuracy afforded by
multiparametric assessment provides a comprehensive framework for the treatment
of these two distinct vocal fold disorders.
PMID- 11007085
TI - Photography of severe laryngeal obstruction.
AB - Thirty-five-millimeter photography using rigid rod lens telescopes at direct
laryngoscopy is the most versatile and reliable method of laryngeal
documentation. Photography of severe laryngeal obstruction, whether in pediatric
or adult patients, mandates a method of anesthesia chosen for maximum patient
safety, a laryngoscope selected for optimal exposure, confidence in controlling
the airway, and a technique that does not jeopardize the safety of the patient.
PMID- 11007086
TI - Critical evaluation of neurolaryngological disorders.
AB - Otolaryngological examinations, videostroboscopic image analysis, and laryngeal
electromyography were used as a test battery for a critical evaluation in 80
patients. Vocal fold movements were categorized into mobility, restricted
mobility, immobility with different positions, and overactive movement. Laryngeal
electromyographic examinations were conducted in all patients, and the results
were classified into normal, neuropathic, and myopathic patterns. The
electromyographic data were integrated with videostroboscopic findings,
interpreted with knowledge of biomechanical and electrophysiological mechanisms
of the larynx, and correlated clinically with underlying diseases. It is
suggested that neurolaryngological procedures are most clinically useful when
dictated by a decision-making algorithm.
PMID- 11007087
TI - Argon plasma coagulation for inferior turbinate reduction.
AB - Surgical reduction of the inferior turbinate remains a widely used therapy for
nasal obstruction caused by hyperplastic turbinates. Current methods are costly
and time-consuming, require nasal packing, and cause extended postoperative
swelling. Argon plasma coagulation (APC) is a new, innovative technique in
otorhinolaryngological surgery that is based on high-frequency electrical
current. The current is transmitted through ionized argon gas (plasma) contact
free to the tissue surface and creates a coagulation and devitalization zone with
limited penetration. Forty-five patients with nasal obstruction were treated
under local anesthesia for reduction of the inferior turbinates with APC. Seventy
six percent of the patients reported an improvement of postoperative swelling
within the first week. After 3 months, 86% reported having better nasal airflow
than they had before the operation. Macroscopically, after 4 weeks the turbinate
was covered by normal mucosa in 51% of the patients. Crust formation was minimal,
and no bleeding occurred. Turbinate reduction with APC is an alternative
technique with many advantages, and the results are comparable to those of
standard techniques. Ninety-five percent of the patients were satisfied with the
operation.
PMID- 11007088
TI - Postoperative radiotherapy in patients with positive nodes after functional neck
dissection.
AB - A study was designed to assess the usefulness of postoperative radiotherapy (RT)
in patients with surgically treated laryngeal and hypopharyngeal cancer with
histologically proven positive neck nodes. Patients underwent operation between
1984 and 1995, with functional neck dissection (FND) being part of the treatment
in all cases. The selection criteria included squamous cell carcinoma, negative
margins for the primary tumor, and no previous treatment. For evaluation
purposes, patients were divided into 2 groups: surgery alone versus surgery with
postoperative RT. Eighty-three patients fulfilled the inclusion criteria and
entered the study. All but 1 of the patients were men. The mean age was 58 years
(range, 35 to 77 years). A multivariate analysis was used to analyze the
prognostic parameters selected by univariate analysis, eg, age, alcohol, tumor
location, T and N stages, and presence or absence of extracapsular spread and a
desmoplastic pattern. Postoperative RT was not selected by univariate analysis as
a prognostic factor, but was included in the multivariate analysis in order to
assess its impact on survival and recurrence rates. Using the statistical method
of multivariate analysis, we could not find evidence of a benefit to survival or
local recurrence rates with postoperative RT in this series. Patients younger
than 55 years and those with extracapsular spread had a decreased survival rate
and a higher neck recurrence rate, irrespective of the treatment method.
PMID- 11007089
TI - Facial nerve: vascular-related anatomy at the stylomastoid foramen.
AB - We dissected 30 facial nerves in fresh cadavers after arterial casting with red
latex to provide specific information about the arterial-related anatomy of the
trunk of the facial nerve from the stylomastoid foramen to its bifurcation. We
found that a wide anatomic variability does exist. The trunk of the facial nerve
was in proximity to the stylomastoid artery, which originated from the posterior
auricular artery in 70% of the specimens (21/30), from the occipital artery in
20% (6/30), and directly from the external carotid artery in 10% (3/30). The
stylomastoid artery passed medially to the trunk of the facial nerve in 63 of the
specimens (19/30) and laterally in 37% (11/30). Among these 11 specimens, 8 were
large-caliber stylomastoid arteries. During parotid surgery, the main trunk of
the facial nerve may be difficult to identify, because a large-caliber
stylomastoid artery can mask it. Therefore, it is important to dissect this
artery with caution.
PMID- 11007090
TI - Postoperative headache after surgery for vestibular schwannoma.
AB - Postoperative headache was studied among 251 patients who underwent operation for
vestibular schwannoma. A questionnaire based on the McGill Pain Questionnaire and
the Finnish Pain Questionnaire was sent to the patients. Twenty-one expressions
describing postoperative headache were extracted with a factor analysis. The pain
intensity was expressed on a visual analog scale, and the risk factors for
postoperative headache were evaluated. Immediately after the operation, 154
subjects reported headache. Eighty-nine of the patients had had headache before
operation, whereas 65 patients experienced headache only after operation. An
average of 8.9 years after surgery, 93 patients still reported headache. Headache
was a major problem for 27 subjects; 18 of the 27 had suffered from headache
before operation. A retrosigmoidal approach, postoperative gait problems,
preoperative headache, and small tumor size predicted postoperative problems with
headache. When headache is present before operation, it tends to continue after
operation, and if headache continues for 1 year, it usually persists without
being reduced.
PMID- 11007091
TI - Artifactual thickening of the sinus walls on computed tomography: a phantom model
and clinical study.
AB - Measuring sinus wall thickness on computed tomography may be important for
distinguishing between acute and chronic inflammation of the paranasal sinuses or
in cases of a suspected neoplasm. The objective of this study was to investigate
the effects of opacified and aerated sinuses on the appearance of sinus wall
thickness. A phantom model consisting of a skull half-immersed in water was
scanned, and various slice thicknesses and different windows were used. The sinus
walls of the water-immersed side appeared to be thicker than those of the aerated
side. Bone windows did not completely eliminate this partial volume effect. It
was concluded that comparison between a fluid- or tissue-filled sinus and an air
filled counterpart is not accurate enough for evaluating sinus wall thickness.
Bone windows do not completely eliminate the artifactual thickening of the bony
wall of a filled sinus.
PMID- 11007092
TI - Management of large Mohs defects.
AB - This study was performed to determine the appropriateness and relative merits of
closing Mohs defects of the head and neck at the time of surgery or after
surgery, in contrast with allowing defects to heal spontaneously. For 185
patients who had large Mohs wounds of the head and neck (scalp, nose, cheek,
forehead, lip, chin, ear, or neck) that healed spontaneously and who underwent
postoperative reconstruction as required, we recorded wound location, size, and
depth. We then evaluated the cosmesis and functional result periodically and > or
= 6 months after operation by chart review, interview, or both. We found that
large wounds of the scalp, neck, and ear (except through-and-through defects)
often heal spontaneously with acceptable cosmesis. Large defects of the nose
usually require prompt reconstruction. Large defects of the central cheek, lip,
and chin usually heal spontaneously with poor cosmesis. However, we often reserve
surgery for an unacceptable cosmetic result, because repairing a small scar is
often less complex than reconstructing a large Mohs defect. We conclude that
spontaneous healing of selected Mohs wounds of the head and neck can result in
satisfactory cosmesis and function, thus obviating or minimizing the need for
complex surgical repair. Surgeons can select management of Mohs wounds
effectively and efficiently by accurately predicting the final cosmetic and
functional result of spontaneous healing, thus reserving surgery for unfavorable
cosmetic or functional results.
PMID- 11007093
TI - Treatment of nasal polyposis in Byzantine times.
AB - The goal of this study was to describe the therapeutic methods and surgical
techniques used during Byzantine times (AD 324-1453) for a disease that has
occupied physicians since antiquity: nasal polyps. The original Greek-language
texts of the Byzantine medical writers, most of which were published after the
17th century, were studied in order to identify the early knowledge of the
definition, symptoms, conservative treatments, and surgical intervention in cases
of this disease. A considerable number of conservative treatments, etiologic and
local (with inunctions or blowing of caustic substances), with evident influence
from Roman medicine, were identified even in the early Byzantine medical texts
(4th century). Further, some surgical techniques were described that seem to
constitute evolution of the Hippocratic tradition. From the study of the original
texts of Byzantine medical writers, their interest in the rhinological diseases
is evident; in the case of nasal polyps, new techniques were mentioned. The first
meticulous intranasal surgical removal of polyps was described. These techniques,
obviously developed during the Hellenistic period, initially influenced European
medicine and later the rest of the world.
PMID- 11007094
TI - Meningitis due to acute otitis media and arachnoid granulations.
PMID- 11007095
TI - Malignant triton tumor of the ethmoid sinus and nasal cavity.
PMID- 11007096
TI - Delayed gastric emptying in human immunodeficiency virus infection: correlation
with symptoms, autonomic function, and intestinal motility.
AB - Gastric emptying may be delayed in HIV infection. We aimed to characterize the
pattern of gastric emptying in HIV seropositive subjects and correlate the
findings with symptoms, as well as to identify possible etiological factors.
Solid gastric emptying was measured using scintigraphy in 54 HIV seropositive
subjects and 12 HIV seronegative controls. Gastrointestinal symptoms were
evaluated using a standardized numerical score, and autonomic function was
assessed using spectral analysis of heart rate variability. Fasting and
postprandial duodenojejunal activity was recorded using strain gauge manometry
catheters. Gastric emptying rate, but not lag phase, was significantly delayed in
HIV-infected subjects, particularly those with enteric infections and more
advanced disease. Delayed gastric emptying did not correlate with symptoms,
autonomic dysfunction, or small intestinal motility. In conclusion, abnormalities
found in autonomic function and gastric emptying in HIV infection are
multifactorial in nature. The contribution of upper gastrointestinal motor
dysfunction to gastric symptoms in such individuals is unclear.
PMID- 11007097
TI - Histomorphometry and strain distribution in pig duodenum with reference to zero
stress state.
AB - The morphometry at no-load and zero-stress states and residual circumferential
strains were determined along the pig duodenum in vitro in seven pigs. The no
load state was obtained by cutting eleven 2-mm-wide rings at 10% intervals along
the duodenum. The zero-stress state was obtained by cutting the rings radially.
The zero-stress state provides a standard morphological state to describe tissue
since internal and external forces do not affect the tissue. The morphometric
measures were obtained from digitized images, and the layer thicknesses were
measured from histological sections. The mucosal and serosal circumferences, the
wall thickness, and the wall thickness-to-mucosal radius ratio were largest in
the proximal end of the duodenum (f > 1.9, P < 0.05). The thickness of the
submucosal stratum compactum layer and the opening angle increased in distal
direction (f = 2.3, P < 0.05 and = 6.5, P < 0.001). The residual strain at the
mucosal surface was negative, indicating that the mucosa-submucosa layers of
duodenum in no-load state are in compression. Distension experiments showed that
the residual strain makes the stress distribution through the wall more uniform
in the pressurized state. In conclusion, the large circumferential residual
strains must be taken into account in the study of physiological problems, in
which the stresses and strains are important, eg, the bolus transport function.
PMID- 11007098
TI - Determinants of occurrence and volume of transpyloric flow during gastric
emptying of liquids in dogs: importance of vagal input.
AB - The precise factors and their relative contributions that lead to individual flow
pulses across the pylorus during liquid gastric emptying remain unclear. Our
objective was to determine the factors leading to individual flow pulses, their
relative contributions and the role of the vagus nerve in their modulation.
Proximal gastric tone had a strong positive correlation with the volume of the
corresponding transpyloric flow pulse whereas pyloric tone had an inverse
correlation. Antral contractions were associated with the presence but not the
volume of the pulse. Acute vagal blockade retarded emptying via loss of proximal
gastric tone and increased outflow resistance and loss of propagating antral
pressure waves. In conclusion, the major determinants of the volume of pulsatile
transpyloric flow are proximal gastric and pyloric tone. The vagus nerve plays a
key role in regulating both proximal gastric and pyloric tone as well as
moderating propagating antral contractions.
PMID- 11007099
TI - Alterations of GTP-binding proteins (Gsalpha and Gq/11alpha) in gastric smooth
muscle cells from streptozotocin-induced and WBN/Kob diabetic rats.
AB - We investigated possible impairment of the signal transduction system in gastric
myocytes of streptozotocin-induced diabetic (STZ) and spontaneous diabetic
WBN/Kob (WBN/Kob) rats. Gastric motility 10 weeks after the onset of diabetes
mellitus was significantly reduced in both diabetic rats compared with control,
and the decreased motility was not recovered by the administration of insulin to
maintain normal blood glucose levels. There was no significant difference between
both types of diabetic rats and control rats in total number of [3H]quinuclidinyl
benzilate ([3H]QNB) binding sites (Bmmax: 545-587 fmol/mg protein) on gastric
smooth muscle cell membranes or in the affinity of [3H]QNB for the binding sites
(Kd: 0.06-0.07 nM). Immunoblot analysis using polyclonal anti-G-protein
antibodies indicated increased expression of Gsalpha in gastric smooth muscle
cell membranes, but no significant change in Gialpha or Gq/11alpha expression in
STZ rats, and decreased expression of Gq/11alpha with no significant change in
Gsalpha and Gialpha in WBN/Kob rats. The cAMP production in gastric smooth muscle
cell membranes was augmented in the absence and presence of 100 microM
isoproterenol, and 100 microM forskolin in STZ rats, whereas no significant
change of cAMP production was observed in WBN/Kob rats irrespective of the
presence of the stimulants. These findings suggest that long-standing diabetes
may induce alterations in signal transduction at downstream receptors in gastric
myocytes, resulting in the impairment of gastric motility, although the mechanism
of reduced contractile activity may differ between STZ and WBN/Kob rats.
PMID- 11007100
TI - Distal gastrectomy and Roux-Y limb in the rat: plasma motilin, pancreatic
polypeptide concentrations, and duodenojejunal motility.
AB - After gastrectomy, Roux-Y limb reconstruction leads to duodenojejunal motor
disturbances. Because motilin and pancreatic polypeptide (PP) play a role in the
regulation of digestive motility, their plasma concentrations were determined in
rats after Roux-Y gastrectomy. Three months after a distal Roux-Y gastrectomy,
coupling of electromyographic recordings and jugular samples were used to perform
motilin and PP radioimmunoassays during and between activity fronts (AFs)
occurring in the limb and in the duodenojejunum, 20, 40, and 60 min after
intragastric instillation of a standard meal (5 ml Realmentyl). Animals that
underwent a simple laparotomy, animals having isolated jejunal transection, and
animals with Billroth I gastrectomy (BI group) served as control groups. After
Roux-Y gastrectomy, the number of AFs in the limb (P < 0.01) and in the duodenum
(P < 0.001) was reduced compared to laparotomized rats and the BI group, but did
not differ from the number in the Tr group. In the limb, AFs were incompletely
propagated or were retrograde in 9 and 3 of 20 animals, respectively. After Roux
Y gastrectomy, motilin concentrations occurred at the same time as each duodenal
AF, and as in controls, and were independent from AFs in the limb. Plasma motilin
concentrations were higher after Roux-Y reconstruction than in control groups (P
< 0.03), and PP level concentrations were not different. After the meal, the
interruption of AFs was shorter in Roux-Y reconstruction than in laparotomized
and transected animals (P < 0.05) and than in BI group, with no significant
difference in the latter. In all groups, plasma motilin and PP concentrations
were decreased (P < 0.05) and increased (P < 0.001), respectively, after the meal
compared to the interdigestive period. After Roux-Y gastrectomy, plasma motilin
and PP levels were higher (P < 0.05) and lower (P < 0.05), respectively, compared
to controls. In conclusion, AFs in the Roux-Y limb were not associated with
plasma motilin concentrations, suggesting a lack of influence of motilin on the
interdigestive motor status. The decrease in postprandial plasma PP
concentrations may play a role in the shorter interruption of AFs after a meal.
PMID- 11007101
TI - Association of Zollinger-Ellison syndrome with pancreatitis: report of five
cases.
AB - In a retrospective analysis, five cases of Zollinger-Ellison syndrome were found
in a typical urban inner-city teaching hospital. Chronic alcohol abuse and heavy
smoking characterized these patients, and four of them also had pancreatitis,
suggesting an association of gastrin-producing tumors and pancreatic
inflammation. Ductal obstruction by neuroendocrine tumors has been reported to
cause pancreatitis in a few cases. In this analysis, however, a nonobstructive
gastrinoma was the surgical diagnosis in three patients, and it was suggested by
imaging studies in the two other cases. The potential other pathomechanisms for a
dual cause-effect relationship of gastrinoma and pancreatitis are discussed.
PMID- 11007102
TI - P-selectin expression and Kupffer cell activation in rat acute pancreatitis.
AB - This work studied the activation of hepatic macrophages during acute pancreatitis
and the involvement of these cells in the lung inflammatory response.
Pancreatitis was induced in Wistar rats by intraductal administration of 5%
sodium taurocholate. Three hours after pancreatitis induction, the degree of
pulmonary inflammation, TNF-alpha levels, and P-selectin expression were
evaluated. The generation of TNF-alpha by Kupffer cells was also measured.
Pancreatitis increases the serum concentration of TNF-alpha, neutrophil
infiltration, and P-selectin expression in pancreas and lung. In addition,
Kupffer cells generate increased levels of TNF-alpha. When Kupffer cells were
inhibited, the increase in serum TNF-alpha levels and the infiltration of
neutrophils in the lung were prevented, but P-selectin expression remained
unmodified. We conclude that pulmonary inflammation induced by acute pancreatitis
is mediated by Kupffer cell activation and that pancreatitis induces the
expression of P-selectin on pulmonary endothelial cells but this effect is not
mediated by Kupffer cells.
PMID- 11007103
TI - Chronic hyperlipasemia caused by sarcoidosis.
AB - A chronically elevated lipase is a rare biochemical finding and has only
previously been described in patients with malignancy and macrolipasemia. We
report a case of chronic hyperlipasemia caused by sarcoidosis. The literature on
pancreatic sarcoidosis is reviewed and the significance of lipase isoforms is
discussed. Sarcoidosis needs to be considered in patients presenting with chronic
hyperlipasemia.
PMID- 11007104
TI - Efficacy of lactulose in cirrhotic patients with subclinical hepatic
encephalopathy.
AB - To investigate the role of lactulose in the treatment of cirrhotic patients with
subclinical hepatic encephalopathy (SHE), 40 cirrhotic patients, 33 males and 7
females, were included in the study. The diagnosis of SHE was made by
quantitative psychometric tests including the number connection test (NCT),
figure connection test (FCT) parts A and B, and two performance subtests of
Wechsler adult intelligence scale, ie, picture completion (PC) and block design
(BD) tests. SHE was diagnosed in 26 (65%) of 40 patients. Of these 26 patients,
14 patients were randomized to treatment group (lactulose 30-60 ml/day for three
months, SHE-L) and 12 patients to no treatment group (no lactulose, SHE-NL).
Psychometric tests were repeated in all patients in both groups and in six
patients with no SHE (group NSHE, N = 14) after three months. The mean scores and
number of the abnormal psychometric tests at entry were significantly higher in
patients in groups SHE-L and SHE-NL than in patients in group NSHE; however,
there was no significant difference between SHE-L and SHE-NL. The mean number of
the abnormal psychometric tests decreased in patients in group SHE-L after three
months of treatment with lactulose (2.9 +/- 0.9 vs 0.8 +/- 1.2; P = 0.004);
however, there was no change in patients in group SHE-NL after three months (3.7
+/- 1.5 vs 3.5 +/- 1.3; P = NS). While SHE improved in 8 of 10 patients in group
SHE-L, none of the patients in group SHE-NL improved after three months of follow
up (P < 0.001). Two patients in group SHE-NL also developed overt encephalopathy
during the study period. We conclude that lactulose treatment in cirrhotic
patients with SHE is effective.
PMID- 11007105
TI - Acetaminophen hepatoxicity.
AB - To determine the influence of psychosocial factors in accidental and deliberate
acetaminophen overdose, we reviewed the charts of 207 overdose patients, and 48
met our criteria for acetaminophen toxicity. Two patients died. A psychiatric
history was present in 75%, and 25% had a previous or subsequent suicide attempt.
A substance abuse history was elicited from 46% and 36% of adolescent teenagers
had a teen pregnancy. The mean time to starting N-acetylcysteine was 18.5 hr.
Delayed N-acetylcysteine administration led to higher transaminase levels.
Alcohol abuse was associated with a longer hospital stay. Mean AST was 8,860
IU/liter in the accidental and 3,013 IU/liter in the suicide groups. We concluded
that management of acetaminophen toxicity can be optimized by early
identification, obtaining a complete drug screen, starting N-acetylcysteine early
or whenever toxic acetaminophen levels or elevated transaminases are identified,
and referring patients with acetaminophen toxicity to a liver center.
PMID- 11007106
TI - Ursodeoxycholic acid treatment in abdominal sarcoidosis.
PMID- 11007107
TI - Hyperplastic liver nodules associated with early-stage primary biliary cirrhosis
mimicking hepatocellular carcinoma.
PMID- 11007108
TI - Electrochemotherapy for colorectal cancer with commonly used chemotherapeutic
agents in a mouse model.
AB - We examined here the usefulness of electrochemotherapy against colorectal cancer
(CRC) using a mouse model. Electropermeabilization profoundly increased the
sensitivity of murine CRC, Colon 26, and MC38 cells to bleomycin (BLM) but not to
5-fluorouracil (5-FU) or to cisplatin (CDDP) in vitro. In vivo experiments
revealed that electrochemotherapy with 5-FU, CDDP, or BLM was much more effective
against CRC compared with the treatment of the drug alone. Electrochemotherapy
with BLM or CDDP exhibited profound antitumor effects on subcutaneously
established CRC in mice, and complete tumor regression was observed in five and
four of eight animals, respectively. Electrochemotherapy with 5-FU also had an
impact on CRC development, and complete cure was observed in one of eight
animals. Subsequent analyses revealed that electropermeabilization significantly
increased intratumoral amounts of BLM and CDDP but not 5-FU. These results
indicate that electrochemotherapy may be a promising treatment modality against
CRC.
PMID- 11007109
TI - 5-aminosalicyclic acid and olsalazine inhibit tumor growth in a rodent model of
colorectal cancer.
AB - The ability of 5-aminosalicylic acid and olsalazine to inhibit colonic aberrant
crypts and tumors was investigated in 1,2-dimethylhydrazine-treated rats. The
effect of these drugs on the rates of tumor apoptosis and proliferation was
studied as potential mechanisms for their action. 5-Aminosalicylic acid reduced
the number of aberrant crypt foci by over one third, while olsalazine had no
effect on this parameter. However, both agents effectively reduced tumor number
and load, increased the rate of tumor apoptosis, and reduced the rate of tumor
cell proliferation. In conclusion, 5-aminosalicylic acid and olsalazine are both
ultimately effective chemopreventive agents in this model; however, only 5
aminosalicylic acid inhibited the formation of aberrant crypt foci. The
inhibitory effect of these agents in tumors is related to the inhibition of
proliferation and the induction of apoptosis.
PMID- 11007110
TI - Palliative decompression of obstructive hilar malignancies utilizing an
extrahilar biliary approach.
AB - Hilar cancers carry a dismal prognosis. Palliation of obstructive jaundice in
patients with hilar cancer can be achieved by either surgical or nonsurgical
means. Selection of the appropriate palliative measures is a challenging problem.
Segmental bilioenteric anastomosis procedures were performed on 19 patients with
hilar cancer. Seventeen of the bypasses were done to the segment III duct, known
as the ligamentum teres approach, and two bypasses were to the segment V duct.
Five patients, who had already been stented percutaneously or endoscopically,
were operated on after the stents were clogged and a duodenal obstruction ensued.
There were two postoperative deaths (10.5%) and four postoperative complications
(21%). All of the 17 surviving patients experienced improvement in the level of
jaundice postoperatively and the levels of serum total and direct bilirubin
decreased by 78.9% and 84.2%, respectively. Two patients developed late
cholangitis before death and were treated by external biliary drainage; one
developed duodenal obstruction and was treated by gastrointestinal anastomosis.
The mean length of hospital stay was 15.2 days. Mean survival was 8.2 months and
the mean period of well-being was 7.8 months. Median survival was 7 months and
median period of well being was 7 months. Three patients are still alive at 8, 8,
and 24 months. These data suggest that the ligamentum teres approach offers
effective palliation for patients with unresectable hilar cancer.
PMID- 11007111
TI - Influence of disease site and activity on peripheral neutrophil function in
inflammatory bowel disease.
AB - Reactive oxygen species, released by phagocytes, are involved in tissue injury in
inflammatory bowel diseases. The aim of our study was to evaluate peripheral
neutrophil function in patients with ulcerative colitis (N = 66) and Crohn's
disease (N = 62) with respect to disease activity and extent, using
chemiluminometry after three stimuli. Twenty-seven healthy subjects were enrolled
as controls. Neutrophils from ulcerative colitis and Crohn's disease patients had
a significantly higher response than those from controls following phorbol
myristate acetate (86.6 +/- 6.5, 173.8 +/- 11.9, 167.5 +/- 12.2 mV, P < 0.0001),
formyl-methionyl-leucyl-phenylalanine (39.5 +/- 3.4, 41.3 +/- 2.7, 58.6 +/- 4.7
mV, P < 0.001), and zymosan (142.6 +/- 10.4, 223.7 +/- 8.9, 231.2 +/- 9.5 mV, P <
0.0001) administration. The increased response was observed during both active
disease and remission. The highest chemiluminescence values were found in
patients with active ulcerative pancolitis and ileal Crohn's disease. The
activation of circulating neutrophils may indicate persistent intestinal
inflammation or may be triggered by luminal factors even in the absence of
symptoms.
PMID- 11007112
TI - Sequential group trial to determine gastrointestinal site of absorption and
systemic exposure of azathioprine.
AB - Azathioprine (AZA) is used in the treatment of patients with refractory
inflammatory bowel disease; however, its use is limited because of systemic
toxicity associated with long-term use. Ileocecal delivery of AZA might be
advantageous if local intestinal therapeutic effects could be provided with
decreased systemic side effects. Decreased cecal systemic absorption would allow
higher dosages of AZA to be administered. A two-phase study was performed to
compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following
administration of AZA into the stomach, jejunum, and cecum and to compare the
systemic exposure to AZA and 6-MP following administration of three different
dosages of AZA into the cecum. In phase I, six healthy male volunteers received
three 50 mg sequential doses of AZA via an oral tube directly placed into the
stomach, jejunum, and cecum, respectively. In phase II, six healthy male
volunteers received three different dosages (50, 300, 600 mg of AZA) into the
cecum. Plasma concentrations of AZA and 6-MP at various times were quantified and
area under the plasma concentration-time curve (AUC) and mean residence time
(MRT) were determined. No significant differences in the AUC of AZA were seen at
the different sites. The AUC of 6-MP following administration of AZA into the
jejunum (67.0 +/- 30.1 ng x hr/ml) was higher compared to the stomach (39.9 +/-
38.1 ng/hr/ml) and cecum (29.2 +/- 10.9 ng x hr/ml). Jejunal absorption was 68%
higher than absorption from the stomach and 129% higher than that of the cecum.
Gastric absorption was 27% higher than that of the cecum. Increased dosages given
into the cecum resulted in increased AUCs of AZA and 6-MP. The AUCs of AZA
following 50, 300, and 600 mg dosages were 16.9 +/- 7.4, 52.3 +/- 67.2, and 132
+/- 151 ng x hr/ml, respectively, and the AUCs of 6-MP were 22.2 +/- 14.9, 63.4
+/- 50.6, and 104 +/- 115 ng x hr/ml, respectively. Systemic exposure to 6-MP is
reduced following administration of AZA into the cecum, most likely secondary to
reduced absorption of 6-MP from the colon. Higher dosages of AZA presented to the
cecum do result in increased systemic absorption, but may still allow more drug
to be administered with less toxicity than the same dose received orally.
PMID- 11007113
TI - Rebamipide, an antiulcer drug, prevents DSS-induced colitis formation in rats.
AB - This study was conducted to investigate the efficacy of rebamipide against
experimental colitis induced by dextran sulfate sodium (DSS) in a rat model of
inflammatory bowel disease. Experimental colitis was induced in male Wistar rats
by oral administration of 3% DSS solution for one week. The rats were provided
with standard diet containing 0.105% rebamipide (160 mg/kg/day) for 1 week. In
rats treated with rebamipide, clinical (body weight loss, bloody diarrhea,
reduced physical activity, severe anemia, shortened colonic length, and perianal
injury) and histopathological (pathological lesion score) findings of DSS colitis
were significantly less than in rats with DSS colitis not treated with
rebamipide. Rebamipide thus inhibited the induction of colitis. Rebamipide
significantly reduced concentrations of both interleukin-1alpha and GRO/CINC-1
(IL-8-like substance) and cell infiltrates in colonic wall, in parallel with
decreased activity of myeloperoxidase. It also reduced expression of IL-1 mRNA
but did not influence expression of GRO/CINC-1 mRNA. The attenuation of colonic
indices of colitis by rebamipide in this rat model suggests that this drug might
have beneficial effects in the treatment of human ulcerative colitis. These
effects of rebamipide are attributable to its inhibition of inflammatory cytokine
mediated granulocyte (neutrophil) infiltration into the colon.
PMID- 11007114
TI - Antioxidative effect of intestinal bacteria Bifidobacterium longum ATCC 15708 and
Lactobacillus acidophilus ATCC 4356.
AB - The antioxidative effect of intact cells and intracellular cell-free extracts of
intestinal lactic acid bacteria B. longum (ATCC 15708) and L. acidophilus (ATCC
4356) was investigated. Both intact cells and intracellular cell-free extracts of
10(9)cells of B. longum and L. acidophilus demonstrated antioxidative activity,
inhibiting linoleic acid peroxidation by 28-48%. This indicated that these two
strains demonstrated excellent antioxidative activity. B. longum and L.
acidophilus also showed the ability to scavenge alpha,alpha-diphenyl-beta
picrylhydrazyl (DPPH) free radical, scavenging 21-52%. The intact cells of these
two intestinal bacteria demonstrated a high inhibitory effect on the cytotoxicity
of 4-nitroquinoline-N-oxide (4NQO). Cytotoxicity of 4NQO was reduced by L.
acidophilus by approximately half and by almost 90% by B. longum. Nevertheless,
no inhibition of cytoxicity observed for intracellular cell-free extracts of
10(9) cells of B. longum and L. acidophilus. The effect of B. longum and L.
acidophilus on inhibiting plasma lipid peroxidation was also evaluated. The
results showed that both intestinal strains were able to protect plasma lipid
from oxidation at different degrees. The inhibition rates on plasma lipid
peroxidation ranged from 11 to 29% for 10(9) cells of B. longum and L.
acidophilus. Generally speaking, B. longum demonstrated better antioxidative
ability than L. acidophilus in this study.
PMID- 11007115
TI - Short-chain fatty acids induce cytoskeletal and extracellular protein
modifications associated with modulation of proliferation on primary culture of
rat intestinal smooth muscle cells.
AB - Short-chain fatty acids are the main end products of bacterial fermentation of
carbohydrates. Their role on the metabolism and biology of colonocytes is now
well characterized. However, the functional consequences of their presence on
intestinal smooth muscle cells remain poorly studied. We aimed to assess the
effect of different short-chain fatty acids on ileal and colonic smooth muscle
cells in primary culture and on A7R5 line. Butyrate (above 0.1 mM) inhibited A7R5
cell proliferation, while at low concentration (0.05 to 0.5 mM) butyrate
significantly stimulated the proliferation of ileal and colonic myocytes in
primary culture. An inhibition was observed at higher concentrations. Collagenous
and noncollagenous protein synthesis was stimulated by butyrate. Moreover,
butyrate stimulated actin and myosin expression. Thus, butyrate, which is
produced by dietary fiber fermentation, may affect intestinal muscles by directly
acting at the molecular level on myocytes.
PMID- 11007116
TI - Reaggregation of rat dissociated myenteric plexus in extracellular matrix gels.
AB - The aim of this study was to investigate the growth behavior of freshly
dissociated myenteric plexus in a three-dimensional extracellular matrix (ECM)
environment with and without stimulation of glial cell line-derived neurotrophic
factor (GDNF). Therefore, cell suspensions of the dissected myenteric plexus of
newborn rats were cultured in freshly prepared gels of commercially available
mixtures of collagen, laminin, and hepatoglycans as a first step towards
mimicking the natural environment of the myenteric plexus. The cultures were kept
either in chemically defined serum-free medium alone or supplemented with GDNF.
Cultures on polylysinc-coated glass cover slips served as controls. Dissociated
myenteric plexus grown on polylysine formed dense clusters of neurons with
radially outgrowing nerve fibers, while the neurons cultured in the gel
reaggregated to much smaller clusters. These contained, depending on the culture
conditions, 2-10 neurons. The morphology of the network that was seen in the gels
after a few days in vitro resembled very closely the in situ situation of the
submucous plexus and the myenteric plexus in hypoganglionic children. Electron
microscope investigations showed a high degree of organization with fiber bundles
and vesicle-containing varicosities and growth cones. Independent of the method
of culturing, GDNF obviously influenced the growth behavior of the dissociated
plexus. The size of the ganglia was larger, and the secondary network denser when
GDNF was supplemented. Moreover, the enteric neurons in the gel cultures tended
to be larger in size when treated with GDNF. Three-dimensional cultures of
dissociated myenteric plexus in an ECM gel might be a valuable tool towards the
understanding of the formation of the enteric nervous system during development,
especially considering pathological conditions such as Hirschsprung's disease or
other dysganglionic diseases.
PMID- 11007117
TI - Diagnosis and removal of cecal whipworm infection: case report and review.
PMID- 11007118
TI - Acute on chronic intestinal pseudoobstruction responds to neostigmine.
PMID- 11007119
TI - Influence of smoking and Helicobacter pylori on gastric phospholipids.
AB - Smokers show higher rates of peptic ulcer disease (PUD) than nonsmokers, probably
due to detrimental effects on the gastric mucosa. Surface-active phospholipids
(SPL) are believed to play a key part in gastric cytoprotection. The aim of this
study was to determine the chronic effects of smoking on the gastric SPL and to
relate them to H. pylori (Hp) -induced effects. Gastric juice was aspirated in 52
patients, with normal findings at planned upper gastrointestinal endoscopy, and
concentrations of seven phospholipid subclasses were analyzed. Concentrations of
lysophosphatidylethanolamine (1-PE) were increased (P = 0.006) in smokers
compared to nonsmokers in non-Hp-infected samples. Nonsmokers infected with Hp
showed increased levels of 1-PE (P = 0.01) and phosphatidylinositol (PI) (P =
0.02) compared to subjects not infected. In human gastric juice PI seems to be
the dominating PL subclass, in contrast to the composition in biopsy specimens.
We also found both Hp-infected and smoking subjects to have higher concentrations
of more polar phospholipid subclasses, ie, 1-PE, making the mucosa more
vulnerable to acid attack as the gastric surfactant becomes less hydrophobic.
PMID- 11007120
TI - Helicobacter pylori seroconversion in asymptomatic blood donors: a five-year
follow-up.
AB - Several techniques have been developed to diagnose Helicobacter pylori infection
and two noninvasive methods are available: carbon 13-urea breath test (UBT) and
serology. Measurement of IgG serum antibodies by enzyme-linked immunosorbent
assay (ELISA) is a reliable and inexpensive method for detection of infection.
The aim of this study was to assess the seroconversion by different techniques
after five to eight years. In 1990, 588 of 1,010 asymptomatic donors were found
to be seronegative by ELISA, based on an H. pylori whole-cell suspension lysate
(sensitivity and specificity: 92% and 97%). In 1995 serum samples from 418 of 588
seronegative donors were collected and retested using the same antigen. 411 of
418 samples were frankly negative, and 7 donors were found to be seroconverted.
This group of seven sera represents the object of the study. They were retested
by ELISA and western blotting using a different antigen (NCTC). To standardize
our techniques, sera from 43 H. pylori positive and 47 H. pylori negative
patients according to culture, histology, urease test, and UBT were used. The
cutoff for ELISA-NCTC was 0.53 AI (absorbance index) (mean value + 2 SD), and for
western blotting was negativity for CagA or <10 bands (sensitivity and
specificity: 95% and 96%; 98% and 81% for ELISA and western blotting
respectively). According to the results obtained in 1990 and 1995, seven donors
were found to be seroconverted by ELISA using sonicated antigen; in five the
seroconversion was confirmed by ELISA using NCTC antigen and in two there was
concordance with WB. Four of the seven donors were contacted and asked to undergo
UBT and a further serum sample was drawn to be reassessed in 1998. A
seroconversion was found in all four donors by ELISA, while WB and UBT confirmed
the seroconversion in only three of four donors. In conclusion the in-house ELISA
used performed well compared to other theoretically better serologic assays and
confirmed the low seroconversion rate for H. pylori infection in adult
populations living in developed countries.
PMID- 11007121
TI - Use of simultaneous high-resolution endoluminal sonography (HRES) and manometry
to characterize high pressure zone of distal esophagus.
AB - The purpose of this investigation was to separate the high pressure zone (HPZ) of
the distal esophagus into its two components, the intrinsic lower esophageal
sphincter (LES) and the extrinsic crural diaphragm (CD), using simultaneous
esophageal manometry and high-resolution endoluminal sonography. Five normal
subjects were studied during end inspiration using a dual manometry/ultrasound
catheter. The HPZ in the distal esophagus was characterized ultrasonographically
as the CD distally and as an overlap of CD and LES proximally. In four of five
volunteers, the initial distal rise in pressure at the HPZ corresponded to
imaging of CD rather than imaging of the LES. In all subjects, peak pressure
corresponded to an overlap of CD and LES. In conclusion, it is possible to divide
the HPZ into its two components, the LES and CD using simultaneous high
resolution endoluminal sonography and esophageal manometry. During end
inspiration, the CD contributes to the initial distal rise in pressure at the
HPZ. Peak pressure of the HPZ corresponds to an overlap of the LES with the CD.
PMID- 11007122
TI - Method to obtain endoscopic esophageal samples for primary cell culture: focus on
infectious contamination.
AB - Cell culture techniques hold great importance for the development of molecular
biology. However, when used to study oncology, most of the samples come from
surgical specimens. Endoscopy is a interesting alternative to get samples for
culture. We studied a protocol to allow the control of infectious contamination
potentially related to endoscopy, which could preclude it as a method to obtain
cells for culture. Esophageal biopsies from 30 patients were taken through upper
gastrointestinal endoscopy, using a previously flamed forceps, and were
cultivated with and without amphotericin. Our results showed contamination in
3.3% of the wells without the antifungal and in 0.8% of those with it. Regarding
the 30 cases studied, the described protocol was able to provide samples free of
contamination in all of them.
PMID- 11007123
TI - Barrett's esophagus.
AB - Barrett's esophagus occurs more frequently than previously anticipated. Detection
of Barrett's esophagus is by endoscopic biopsy in which normal squamous
epithelium of the esophagus is replaced by a specialized columnar epithelium of
any length. Patients with more than five years of gastroesophageal reflux
symptoms, particularly those 50 years of age or older, should have upper
endoscopy to detect Barrett's esophagus. With recognition of Barrett's esophagus
as a premalignant lesion, the crucial issue is surveillance for detection of
dysplasia. Although the natural history of dysplasia is incompletely defined, it
is clear that patients with dysplasia have a higher risk for adenocarcinoma than
those without dysplasia. Dysplasia is not the ideal marker for selecting patients
at high risk for adenocarcinoma, however; recent studies have shown that p53
protein accumulation appears to be earlier and more specific/sensitive marker of
malignant potential in Barrett's esophagus. Management of Barrett's esophagus
often involves a multidisciplinary evaluation and its current status is reviewed.
PMID- 11007124
TI - Geranylgeranylacetone protects cultured guinea pig gastric mucosal cells from
indomethacin.
AB - One of the major side effects of nonsteroidal antiinflammatory drugs, such as
indomethacin, is gastropathy. The purpose of this study was to search for a
therapeutic drug to prevent this side effect in vitro. We found that
geranylgeranylacetone, a unique antiulcer drug with a heat-shock protein-inducing
ability, protected cultured guinea pig gastric mucosal cells from cell damage
caused by indomethacin. This cytoprotective effect of geranylgeranylacetone
required concentrations of more than 10(-6) M and incubation periods of longer
than 2 hr. Pretreatment of cells with an inhibitor of protein synthesis
completely abolished the cytoprotective effect of geranylgeranylacetone,
suggesting that some proteins induced by the drug are responsible for the
cytoprotection. Since pretreatment of cells with low concentrations of ethanol,
which also induced the heat-shock proteins, made cells resistant to indomethacin,
heat-shock proteins are candidates for the proteins that are involved in the
cytoprotective effect of geranylgeranylacetone against indomethacin.
PMID- 11007125
TI - Evaluation of individual symptoms cannot predict presence of gastric
hypersensitivity in functional dyspepsia.
AB - Recently, the concept of gastric hypersensitivity was introduced as an important
factor in the pathophysiology of functional dyspepsia (FD), but it is unclear
which symptoms can predict the presence of gastric hypersensitivity. Therefore,
we evaluated the relationship between common symptoms of FD and various
parameters measured by gastric barostat in FD patients. Gastric barostat tests
were performed in 64 FD patients and 20 healthy control subjects without
gastrointestinal symptoms. Individual symptoms such as early satiety,
postprandial fullness, sense of delayed emptying, nausea, vomiting, and
epigastric soreness were collected and graded as mild to severe. Basal tone,
gastric compliance, and postprandial receptive relaxation were similar in
controls and patients, the threshold of abdominal discomfort was lower in FD
patients than in controls (8.9 +/- 3.6 mm Hg and 14.5 +/- 3.7 mm Hg,
respectively, P < 0.05). However, there were no significant differences in the
threshold of abdominal discomfort according to the severity of individual
symptoms. In conclusion, a simple evaluation of individual symptoms could not
predict the presence of gastric hypersensitivity.
PMID- 11007126
TI - Cyclic nucleotide-gated channels in non-sensory organs.
AB - Cyclic nucleotide-gated channels represent a class of ion channels activated
directly by the binding of either cyclic-GMP or cyclic-AMP. They carry both mono
and divalent cations, but select calcium over sodium. In the majority of the
cases studied, binding of cyclic nucleotides to the channel results in the
opening of the channel and the influx of calcium. As a consequence, cytosolic
free calcium levels increase leading to the modifications of calcium-dependent
processes. This represents and important link in the chain of events leading to
the physiological response. Cyclic nucleotide-gated channels were discovered in
sensory cell types, in the retina, and in olfactory cells, and were extensively
studied in those cells. However, it is becoming increasingly evident that such
channels are present not only in sensory systems, but in most, if not all, cell
types where cyclic nucleotides play a role in signal transduction. A hypothesis
is presented here which attributes physiological importance to these channels in
non-sensory organs. Four examples of such channels in non-sensory cells are
discussed in detail: those in the liver, in the heart, in the brain, and in the
testis with the emphasis on the possible physiological roles that these channels
might have in these organs.
PMID- 11007127
TI - Histamine evoked sustained elevations of cytosolic Ca2+ in bovine adrenal
chromaffin cells independently of Ca2+ entry.
AB - Whole-cell patch-clamp experiments and optical measurements with the Ca2+
fluorescent dye fura-2 were performed to examine histamine induced cytosolic Ca2+
changes in bovine adrenal chromaffin cells. The purpose of this study was to find
out whether the sustained plateau phase, which followed the rapid transient
increase, was due to Ca2+ influx. The extracellular Ca2+ dependence appeared to
be minor, because substitution of Ca2+ with EGTA or BAPTA did not cause obvious
changes in the biphasic Ca2+ response. Application of histamine in a Mn2+
containing external solution did not quench the fura-2 signal. It was neither
possible to detect a histamine induced depolarisation, nor a Ca2+ permeable
current. Changing the driving force for Ca2+ during the plateau phase did not
result in a correlating fura-2 signal. Metal ions like Cd2+, La3+ and Co2+ which
are known to block Ca2+ influx were unable to abolish the typical histamine
induced Ca2+ response. These results suggest that primarily intracellular Ca2+
was responsible for generating the characteristic biphasic Ca2+ response due to
histamine in bovine adrenal chromaffin cells.
PMID- 11007128
TI - Spatial and temporal aspects of ACh-induced [Ca2+]i oscillations in porcine
tracheal smooth muscle.
AB - This study evaluated the relationship between regional elevation in intracellular
calcium concentration ([Ca2+]i) induced by acetylcholine (ACh) and the global
cellular responses in porcine tracheal smooth muscle (TSM) cells. Regional
(approximately 1.5 microm3) and global (whole cell) changes in [Ca2+]i were
measured in fluo-3 loaded TSM cells using real-time confocal microscopy. Regional
responses appeared as propagating [Ca2+]i oscillations whereas global responses
reflected the spatiotemporal integration of these regional responses. Within a
region, [Ca2+]i oscillations were 'biphasic' with initial higher frequencies,
followed by slower steady-state oscillations. With increasing ACh concentration,
the peak (maximum value relative to 0 nM) of regional [Ca2+]i oscillations
remained relatively constant, whereas both frequency and propagation velocity
increased. In contrast, the global spatiotemporal integration of the regional
oscillatory responses appeared as a concentration-dependent increase in peak as
well as mean cellular [Ca2+]i. We conclude that the significance of ACh-induced
[Ca2+]i oscillations lies in the establishment of mean [Ca2+]i level for slower
Ca2+-dependent physiological processes via modulation of oscillation frequency
and propagation velocity.
PMID- 11007129
TI - Norepinephrine acts on the KATP channel and produces different effects on [Ca2+]i
in oscillating and non-oscillating HIT-T15 cells.
AB - Norepinephrine (NE) is an inhibitor of insulin secretion that acts, in part, by
decreasing intracellular free calcium ([Ca2+]i). We examined the effects of NE on
[Ca2+]i in individual HIT-T15 cells loaded with indo 1. Cells were categorized as
oscillators or non-oscillators on the basis of the pattern of the calcium
response to glucose and the effect of NE on [Ca2+]i was subsequently measured in
each cell. NE caused a simple decrease in [Ca2+]i in nonoscillators. In
oscillators, NE decreased the amplitude and frequency of the oscillations.
Furthermore, the duration of the NE effect in oscillators was longer than in non
oscillators. NE did not affect the rise in [Ca2+]i elicited by depolarizing
concentrations of 20 mM or 35 mM KCl alone, or in the presence of 20 mM KCl, 100
microM diazoxide, and 10 mM glucose. In other experiments, NE had no effect on
[Ca2+]i when the KATP channels were fully clamped with diazoxide or tolbutamide.
We conclude that the action of NE to decrease [Ca2+]i in both oscillators and non
oscillators is mediated via activation of the KATP channel. Despite this common
mechanism, NE exerts different effects on oscillating and non-oscillating cells.
PMID- 11007130
TI - Effects of elevated cytoplasmic calcium and protein kinase C on endoplasmic
reticulum structure and function in HEK293 cells.
AB - In human embryonic kidney (HEK) cells stably transfected with green fluorescent
protein targeted to the endoplasmic reticulum (ER), elevation of intracellular
Ca2+ ([Ca2+]i) altered ER morphology, making it appear punctate. Electron
microscopy revealed that these punctate structures represented circular and
branched rearrangements of the endoplasmic reticulum, but did not involve obvious
swelling or pathological fragmentation. Activation of protein kinase C with
phorbol 12-myristate 13-acetate (PMA), prevented the effects of ionomycin on ER
structure without affecting the elevation of [Ca2+]i. These results suggest that
protein kinase C activation alters cytoplasmic or ER components underlying the
effects of high [Ca2+]i on ER structure. Treatment of HEK cells with PMA also
reduced the size of the thapsigargin-sensitive Ca2+ pool and inhibited Ca2+ entry
in response to thapsigargin. Thus, protein kinase C activation has multiple
actions on the calcium storage and signalling function of the endoplasmic
reticulum in HEK cells: (1) reduced intracellular Ca2+ storage capacity, (2)
inhibition of capacitative Ca2+ entry, and (3) protection of the endoplasmic
reticulum against the effects of high [Ca2+]i.
PMID- 11007131
TI - Evaluation of the effectiveness of a specialist nurse in the management of
inflammatory bowel disease (IBD).
AB - OBJECTIVE: To determine the effect of a specialist nurse on the management
outcome of patients with inflammatory bowel disease (IBD). DESIGN: Audit of the
management of a cohort of patients in the year prior to the employment of the
specialist nurse and the year immediately after. SUBJECTS: 339 patients, both
male and female, with either Crohn's disease or ulcerative colitis, resident in
the Cambridge health district. SETTING: Addenbrooke's Hospital NHS Trust
Outpatient Centre. MAIN OUTCOME MEASURE: Health status was measured by blood
tests (C-reactive protein, albumin and haemoglobin) throughout the year, symptom
indices, number of clinic attendances, admissions to hospital and length of stay.
Quality of life was measured via a postal questionnaire. RESULTS: Hospital visits
were reduced from 1377 to 853 (38% reduction) and in-patient length of stay
measured in bed-days from 516 to 417 (19% reduction). The number of patients in
remission increased from 63 to 69%. Patient satisfaction improved in key areas,
in particular, access to information on IBD and advice on avoidance of illness
and maintaining health. Of a total of 251 calls to the telephone helpline, only
19 patients were referred for a medical opinion and five patients required
hospital admission. CONCLUSION: The IBD nurse specialist is a valuable and cost
effective member of the gastroenterology team.
PMID- 11007132
TI - Passive smoking in patients with inflammatory bowel disease: an Israeli
multicentre case-control study.
AB - BACKGROUND: The association between smoking and inflammatory bowel disease (IBD)
is well established. There are, however, no large scale studies of passive
smoking in inflammatory bowel disease and this has never been surveyed in the
Jewish population of Israel. AIM: To study the passive smoking exposure of Jewish
IBD patients in Israel in a large scale multicentre study. METHODS: Patients with
established IBD, aged 18-70 years, were interviewed regarding smoking and other
habits. Two controls, one clinic and one neighbourhood, matched by age, sex,
community group, and education, were sought for each subject. RESULTS: Five
hundred and thirty-four patients (273 ulcerative colitis (UC) and 261 Crohn's
disease (CD)), 478 clinic controls and 430 community controls were interviewed.
There were no significant differences in the passive smoking habits between IBD
patients and their controls. Fifty-one percent of UC patients, 50% of the clinic
controls and 58% of the community controls were exposed to passive smoking at
home (NS); similar results were found among CD patients (50%, 55% and 56%,
respectively). When a quantitative exposure index was used UC patients were
significantly less exposed to passive smoking than were their community controls
(7.46 +/- 8.40 vs 9.36 +/- 9.46, n = 229, P< 0.031). There was no difference in
the exposure to passive smoking among CD patients and their controls. No
differences in exposure to passive smoking were found when UC patients who had
never smoked were compared with their controls. When the quantitative index was
used 'never-smoked' CD patients tended to be less exposed to passive smoking at
home than their community controls (5.40 +/- 7.60 vs 8.04 +/- 8.72, P < 0.05).
CONCLUSION: There is a lack of association between passive smoking and IBD in
Jewish patients in Israel. When a quantitative exposure index was used UC
patients were found to be less exposed to passive smoking than their community
controls.
PMID- 11007133
TI - Symptoms discriminate irritable bowel syndrome from organic gastrointestinal
diseases and food allergy.
AB - BACKGROUND: The value of specific gastrointestinal symptoms in discriminating
irritable bowel syndrome (IBS) from organic disease has been documented. In
contrast, there have been few attempts to identify symptoms that discriminate
irritable bowel syndrome from food allergy, despite similarities in their
respective symptom complexes. We aimed to investigate the value of symptoms in
discriminating irritable bowel syndrome from organic disease and food allergy.
METHODS: Subjects (n = 288) were recruited from consecutive patients presenting
to the Internal Medicine, Gastroenterology and Allergy Units in Chieti. Patients
completed the validated Bowel Disease Questionnaire (BDQ) prior to an independent
diagnostic evaluation, which included endoscopy when appropriate. Food allergy
was diagnosed using a 2-week elimination diet, followed by a placebo-controlled
food challenge test, a skin prick test and serum RAST for specific IgE for
suspected foods or additives. The results of the BDQ were not considered in
formulating a diagnosis. In total, 99 patients were diagnosed with the IBS, 79
patients were diagnosed with organic disease and 22 patients were diagnosed with
food allergy. A further 88 patients with extraintestinal allergies were included
as a control group. RESULTS: Based on logistic regression analysis, six symptom
items discriminated IBS from organic disease, while five symptoms discriminated
patients with IBS from control subjects. A diagnosis of IBS compared to organic
disease was positively associated with straining on defaecation (P=0.0001),
diarrhoea (P=0.001) and abdominal bloating (P=0.01), but was negatively
associated with pain in the upper abdomen (P=0.0004), reflux (P=0.0001) and
appetite loss (P=0.004). A diagnosis of IBS compared to extraintestinal allergy
was positively associated with pain relieved by bowel movement (P=0.0001), pain
in the lower abdomen (P=0.0006), pain in both the upper and lower abdomen
(P=0.003), frequent pain (P=0.001) and abdominal bloating (P=0.0009). In
comparison between IBS and food allergy patients, a diagnosis of IBS was
positively associated with pain in the lower abdomen (P=0.001), pain relieved by
bowel movements (P=0.001), frequent pain (P=0.02) and abdominal bloating
(P=0.03). CONCLUSION: Symptoms appear to be useful for discriminating IBS from
organic gastrointestinal disease and food allergy.
PMID- 11007134
TI - Chondrex (YKL-40), a potential new serum fibrosis marker in patients with
alcoholic liver disease.
AB - OBJECTIVES: Chondrex (YKL-40) is a mammalian member of a protein family that
includes bacterial chitinases. The pattern of its expression in certain tissues
such as human liver or cartilage suggests a function in remodelling or
degradation of extracellular matrix. The purpose of this study was to assess
whether circulating YKL-40 might be a serum fibrosis marker in alcoholics.
METHODS: Plasma YKL-40 was determined in 146 consecutive heavy drinkers (106 men,
40 women; mean age, 49.2 +/- 9.0 years). Liver biochemical parameters and serum
fibrosis markers such as hyaluronate were also measured. Fibrosis and
inflammation in liver biopsy were evaluated using a semi-quantitative scoring
system. RESULTS: Plasma YKL-40 increased in parallel with the severity of
fibrosis (P<0.00001). YKL-40 also increased in the presence of hepatic
inflammation (P<0.01). Receiver operating characteristic curves of Chondrex
revealed that a threshold of 330 microg/l gave a specificity of 88.5%; however,
the sensitivity was only 50.8%. Only 11.5% of patients without severe fibrosis
displayed a Chondrex plasma level above this threshold. A positive correlation
was found between Chondrex and hyaluronate (r=0.40, P<0.0001), and a negative
correlation was shown between Chondrex and the prothrombin index (r=-0.37,
P<0.0001). CONCLUSIONS: The severity of liver fibrosis is associated with
elevated circulating Chondrex levels. The overlap in YKL-40 values prevents use
of Chondrex in a screening programme. High levels of Chondrex (above 330
microg/l) are predictive of severe liver fibrosis. Increased plasma YKL-40 may
reflect the remodelling of liver fibrosis in alcoholics.
PMID- 11007135
TI - The impact of chronic hepatitis B viral infection on gastrointestinal motility.
AB - OBJECTIVES: Disturbed gastrointestinal (GI) motility probably exists in alcoholic
cirrhotic patients; however, the influence of chronic hepatitis B virus (HBV)
infection on GI motility remains unknown. The purpose of this prospective study
was to determine the impact of chronic HBV infection on human GI transit, and to
explore the possible patient factors modulating GI motility. METHODS: We used a
non-invasive hydrogen breath test measuring the oro-caecal transit time (OCTT) to
assess the GI motility in 45 asymptomatic HBV carriers, 26 patients with chronic
hepatitis B, 23 patients with HBV-related liver cirrhosis, and 45 age- and sex
matched healthy volunteers. Their clinical symptoms and various blood parameters,
such as platelet count, prothrombin time, etc. were recorded. Plasma substance P,
nitrate/nitrite and endothelin-1 levels were also measured. RESULTS: The OCTTs in
controls, HBV carriers, chronic hepatitis B and liver cirrhosis patients were
(mean +/- SEM) 78.4 +/- 5.8, 80.9 +/- 4.2, 93.9 +/- 8.8 and 106.5 +/- 12.4 min,
respectively. The OCTT was delayed in patients with HBV-related liver cirrhosis
compared to that of controls (P=0.039). Among the cirrhotic patients,
presentation with ascites delayed OCTT (145.7 +/- 27.2 versus 91.3 +/- 11.9 min,
P=0.039). Neither Child- Pugh grade, portal hypertension, various blood
parameters, plasma substance P, nitrate/nitrite or endothelin-1 levels had any
influence on OCTT. CONCLUSIONS: HBV infection alone does not alter GI motility,
whereas the patients with liver cirrhosis may have delayed GI motility. Ascites
is most likely a factor responsible for the delayed GI transit among chronic HBV
infected subjects.
PMID- 11007136
TI - Decrease of regional cerebral blood flow in liver cirrhosis.
AB - OBJECTIVE: Alterations of regional cerebral blood flow (rCBF) in subjects with
liver cirrhosis have not been fully evaluated. We evaluated quantitative changes
in rCBF using single photon emission computed tomography (SPECT). METHODS: Twenty
eight Japanese patients with liver cirrhosis were enrolled in this study. None of
them exhibited advanced hepatic encephalopathy at the time of examination. The
cause of liver cirrhosis was viral infection in 26 patients; the cause was
unknown in two patients. Child-Pugh classification of the patients was as
follows: Group A, 12 patients; Group B, 12 patients; and Group C, four patients.
The control group consisted of 25 age-matched healthy subjects. Radionuclide
angiography was performed by rapid injection of Tc-99m ethyl cysteinate dimer
(ECD) (740 MBq) via the right cubital vein, and then SPECT brain images were
taken. Using the Patlak graphical method, rCBF values (ml/100 g per min) were
calculated in the frontal, parietal, temporal and occipital lobes and cerebellum
on SPECT images. RESULTS: The rCBF values were lower in cirrhotic patients than
in controls, i.e. by 15% in the frontal lobe, by 12% in the parietal lobe, by 10%
in the temporal and occipital lobes, and by 7% in the cerebellum. They decreased
concomitantly with the severity of liver disease. A significant negative
correlation was noted between rCBF values and Child-Pugh score in the frontal
(P<0.01), parietal (P<0.05) and occipital lobes (P<0.01). rCBF values of each
region were not correlated with age or with results of neuropsychological test.
The degree of association between rCBF values and results of laboratory
examination was generally poor. CONCLUSION: Patients with liver cirrhosis without
advanced encephalopathy showed widespread reduction in rCBF; this reduction was
particularly evident in the frontal lobe. Tc-99m ECD SPECT may be useful for
evaluating cerebral functional changes in patients with liver cirrhosis.
PMID- 11007137
TI - Liver injury due to tetrabamate (Atrium): an analysis of 11 cases.
AB - BACKGROUND: Tetrabamate (Atriums), widely used in the treatment of tremor and
ethanol-withdrawal symptoms, has been incriminated as a potential cause of
reversible acute hepatitis. OBJECTIVE: We report here on 11 patients who
experienced tetrabamate-related liver injury, in order to evaluate their
clinical, histopathological and evolutive features. PATIENTS AND METHODS: Between
1987 and 1998, 34 cases of tetrabamate-associated acute hepatitis were
spontaneously reported to the regional pharmacovigilance center of Lyon. Eleven
cases were considered probably to be drug-induced. RESULTS: There were three
males and eight females aged 31-82 years (mean, 57 years). The duration of
treatment ranged from 33 to 206 days, and indication for treatment was depressive
disorders, tremor or prevention of alcohol withdrawal symptoms. Clinical symptoms
were asthenia (n = 9), jaundice (n = 3) and/or diffuse rash (n = 3). The pattern
of liver injury was cytolytic (n = 10) or cholestatic (n = 1). Three patients
presented biological features of hepatic failure. A percutaneous liver biopsy was
performed in six patients. Histological examination of the liver specimen showed
a large spectrum of lesions: massive hepatocellular necrosis (n = 1),
centrilobular and nonconfluent hepatocyte necrosis (n = 2), intracellular
cholestasis (n = 3), and granulomatous hepatitis (n = 1). Tetrabamate was
discontinued in all patients. In seven patients, a complete recovery was observed
3 weeks to 3 months after drug withdrawal. Two patients, despite a rapid
improvement of liver function tests, died from unrelated causes. The remaining
two patients died from irreversible hepatic failure. CONCLUSIONS: Our data
strongly suggest that tetrabamate may induce acute liver injury, which may
eventually result in life-threatening liver failure.
PMID- 11007138
TI - Soda bread provocation test for subjects with transient serology for coeliac
disease 3 years after a population screening survey.
AB - BACKGROUND: We have previously reported that IgA antigliadin antibodies (IgA-AGA)
in the majority of healthy subjects are transient and do not indicate
enteropathy, and also that an increased intake of gluten in the form of soda
bread may be part of the explanation for this phenomenon. OBJECTIVE: The aim of
the study was to determine whether gluten challenge with soda bread in subjects
with transiently positive IgA-AGA could induce a significant titre of IgA-AGA.
DESIGN: Food challenge study. METHODS: All subjects with positive IgA-AGA on
screening at the time of the MONICA project in 1991 (T0) who developed negative
serology at 3-year follow-up (T1) were invited to participate in a 'soda bread
challenge' (1 loaf per day) for 1 month. Analysis of food intake was carried out
prior to the challenge (T2) and compared to the analysis at the time of screening
(T0). IgA-AGA and IgA antiendomysial antibodies (EMA) were checked pre- (T2) and
post-challenge (T3). RESULTS: Ten subjects agreed to participate. Quantities of
food ingested for the various categories did not differ significantly from T0 to
T2. IgA-AGA titres did not differ significantly from T1 to T2 (20.2 versus 35.0,
P=0.085). Mean IgA-AGA titres rose significantly between T2 and T3 (35.0 versus
40.3, P=0.005), although none of the subjects developed a significant titre of
IgA-AGA. None of the subjects were positive for IgA-EMA. CONCLUSIONS: Intake of
soda bread does not appear to be an important explanation as to why subjects may
have a transient rise in IgA-AGA titre since none of the subjects developed a
significant titre of IgA-AGA.
PMID- 11007139
TI - Evidence for existence of coeliac disease autoantigens apart from tissue
transglutaminase.
AB - BACKGROUND: The pathogenesis of coeliac disease (CD) and of dermatitis
herpetiformis (DH) is strongly associated with production of autoantibodies,
defined by indirect immunohistology. Recently, tissue transglutaminase (tTG) was
identified as a prominent autoantigen. It would be important to investigate if
further molecules apart from tTG are involved in autoimmunity. METHODS: Tissue
sections of human foetal intestine were used to compare the distribution of tTG
with the autoantibody binding patterns of 14 sera samples from patients with CD
or DH. Double label experiments were performed using monoclonal as well as
polyclonal tTG antibodies (anti-tTG) and patient sera. The staining was
investigated by using conventional light and confocal laser scanning microscopy.
RESULTS: Most autoantibody binding sites were matched by tTG. Further, the
binding of autoantibodies could be inhibited by preincubation with monoclonal
anti-tTG. However, in nine serum samples (64%) autoantibody staining suggested a
few distinct binding sites apart from tTG. In three sera (21 %) autoantibody
binding fibres were detected which definitely did not match monoclonal anti-tTG
signals. Distinctly stained fibres were confirmed by applying polyclonal anti
tTG. This indicates the existence of autoantigenic epitopes not related to tTG.
PMID- 11007140
TI - Idiopathic fibrosing pancreatitis and Crohn's disease: an interesting
association.
AB - Idiopathic fibrosing pancreatitis is an uncommon condition in children and
adolescents of unknown aetiology. This syndrome has been reported in 36 cases so
far. To our knowledge none of these cases was definitively associated with
Crohn's disease. In this report we describe a young female patient who developed
Crohn's disease of the colon 5 years after having been diagnosed with idiopathic
fibrosing pancreatitis. The differential diagnosis between this syndrome
associated with Crohn's disease and pancreatic Crohn's disease or fibrosing
colonopathy, an entity related to pancreatic enzyme therapy, is discussed.
PMID- 11007141
TI - A case of haemosuccus pancreaticus.
AB - Haemosuccus pancreaticus (Wirsungorrhagia or pseudohaemobilia) is a rare
complication of chronic pancreatitis. We describe a 48-year-old patient with
alcohol-induced chronic calcific pancreatitis and recurrent episodes of severe
upper gastrointestinal bleeding but without abdominal pain. Upper
gastrointestinal endoscopy revealed fresh blood oozing from the ampulla of Vater.
No pseudoaneurysms or pseudocysts were detected by arteriography or computerized
tomography. The bleeding was attributed to pancreatic lithiasis. Following
conservative treatment, there was no evidence of recurrence during a 24-month
follow-up period. In conclusion, although a rare occurrence, haemosuccus
pancreaticus should be considered in the differential diagnosis of all cases of
obscure upper gastrointestinal bleeding in patients with chronic pancreatitis,
whether or not accompanied by pain. A highly suggestive clinical history or X-ray
findings and an endoscopic visualization of blood coming from the ampulla of
Vater may suffice for the diagnosis, thus avoiding diagnostic and therapeutic
errors. When haemosuccus pancreaticus occurs in patients without pseudoaneurysms
or pseudocysts, it can be treated conservatively, thus obviating the need for
pancreatectomy or arteriographic embolization.
PMID- 11007142
TI - Development of small hepatocellular carcinoma 80 months after clearance of
hepatitis C virus with interferon therapy.
AB - We describe a patient who had a complete and sustained response to interferon
(IFN) therapy for chronic hepatitis C but developed small hepatocellular
carcinoma (HCC) 80 months later. A 55-year-old Japanese man with hepatitis C
virus (HCV) infection and histological features of chronic active hepatitis was
treated with recombinant IFN alpha-2a, 9,000,000 U daily for 2 weeks followed by
three times a week for 22 weeks. He successfully responded to IFN therapy with a
normalization of serum alanine aminotransferase and continuous disappearance of
serum HCV-RNA. However, 80 months after the cessation of IFN therapy, the
patient's alpha-fetoprotein (AFP) level became elevated for the first time and
HCC, 12 mm in diameter, was detected by routine ultrasonographic screening.
Laparotomy revealed a small HCC with no metastasis, and the nontumorous liver
demonstrated chronic inactive hepatitis. This case indicates the need for careful
follow-up using ultrasonography and AFP testing for at least 7 years after
completing IFN therapy in all patients with chronic hepatitis C, even if the
patients have a complete response to the therapy.
PMID- 11007143
TI - Gastric adenocarcinoma in a patient with X-linked agammaglobulinaemia.
AB - Patients with primary immunodeficiencies are at high risk for developing
haematological malignancies and, to a lesser degree, carcinoma. We report a
patient with ascertained X-linked agammaglobulinaemia who developed a gastric
carcinoma involving the distal part of the stomach associated with chronic
atrophic gastritis and intestinal metaplasia. These latter conditions are
considered to be precursor conditions and the role of chronic infections is
likely. Patients with X-linked agammaglobulinaemia, as with other primary
immunodeficiencies, could benefit from regular gastrointestinal evaluation,
leading to early diagnosis and treatment of carcinoma.
PMID- 11007144
TI - Multivisceral eosinophilic fibrosis: a new clinical presentation.
AB - We describe a patient who was referred to us with the diagnosis of pancreatic
cancer but who had eosinophilic fibrosis of the pancreas and other organs,
including the sub-mandibular salivary glands, retro-orbital tissue, liver,
kidneys, and surrounding the abdominal aorta. He had no pain or other symptoms.
After treatment with methylprednisolone, all lesions disappeared and now he seems
to be cured of this apparently immune-mediated disorder. To our knowledge,
involvement of all these particular organs by eosinophilic fibrosis in the
absence of symptoms has never before been described.
PMID- 11007145
TI - Cushing's syndrome in an 81-year-old patient treated with budesonide and
amiodarone.
AB - This is the first report of Cushing's syndrome under oral budesonide treatment.
An 81-year-old man known for paroxysmal atrial fibrillation and chronic renal
insufficiency, treated with 6 mg budesonide for collagenous colitis, developed
Cushing's syndrome under co-administration of amiodarone. The Cushing's syndrome
disappeared after discontinuation of the amiodarone treatment. Metabolism of the
two medications by hepatic cytochrome P 450 3A may explain the development of
Cushing's syndrome.
PMID- 11007146
TI - Epidemiology and interventiaonl studies. Helicobacter pylori and gastric cancer:
progression/regression of histopathological lesions.
PMID- 11007147
TI - Transdermal slow-release long-acting isosorbide dinitrate for 'nutcracker'
oesophagus: an open study.
PMID- 11007148
TI - English language use as a risk factor for smoking initiation among Hispanic and
Asian American adolescents: evidence for mediation by tobacco-related beliefs and
social norms.
AB - Acculturation increases the risk of smoking among Hispanic and Asian American
adolescents, but the underlying mechanisms are not understood. This study
examined associations between English language use and smoking among 4,167
Hispanic and 2,836 Asian American adolescents in California. Potential mediators
were assessed, including access to cigarettes, perceived consequences, friends'
smoking, cigarette offers, refusal self-efficacy, and prevalence estimates of
peer smoking. English language use was associated with increased risk of lifetime
smoking in both groups. This association became nonsignificant after access,
perceived consequences, friends' smoking, and offers were controlled for. The
acculturation process (as indicated by English language use) may be associated
with smoking-related psychosocial variables, which may lead to an increased risk
of experimentation with smoking.
PMID- 11007149
TI - Sociodemographic and psychological predictors of changes in dietary fat
consumption in adults with high blood cholesterol following counseling in primary
care.
AB - The associations between sociodemographic variables, psychological factors, and
changes in dietary fat consumption over 4 months were assessed in a randomized
controlled trial of behavioral counseling versus standard advice. Patients were
141 men and 150 women, with an average age of 52.1 years and total cholesterol
level of 7.27 mmol/l (278 mg/dl). Smokers, younger patients, and those with
greater body mass index had higher fat intake at baseline. Behavioral counseling
led to greater reductions in fat intake than did standard advice. Self-efficacy
and ratings of benefits of low-fat diets were related to fat consumption at
baseline, and changes in these measures were correlated with changes in fat
intake. Family support, baseline anticipated regret, and (for the behavioral
counseling group only) baseline behavioral intentions predicted reductions in fat
intake. The results indicated that psychosocial variables associated cross
sectionally with fat consumption do not necessarily predict change and that
factors involved in the process of change and the prediction of change need to be
differentiated.
PMID- 11007150
TI - Gender-linked personality traits predict mental health and functional status
following a first coronary event.
AB - Three gender-linked traits were examined with respect to adjustment to a coronary
event: agency, a focus on the self; communion, a focus on others; and unmitigated
communion, an extreme focus on others to the exclusion of the self. Participants
(n = 65) were interviewed 1 week and 4 months after a 1st coronary event.
Hypotheses were that agency should predict improved health, communion should be
unrelated to health, and unmitigated communion should predict worse health over
time. Outcomes included depression, anxiety, and well-being (as measured by the
Profile of Mood States; D. McNair, M. Lorr, & L. Droppleman, 1971); mental and
physical functioning (SF-36; J. E. Ware, K. K. Snow, M. Kosinski, & B. Gandek,
1993); and cardiac symptoms. Results confirmed hypotheses. In addition,
unmitigated communion was linked with poor health behavior and negative social
interactions, which partly explained the link of unmitigated communion with
depression and cardiac symptoms.
PMID- 11007151
TI - Job strain and risk indicators for cardiovascular disease in young female nurses.
AB - This study examined the possible effects of job demands, decision latitude, and
job-related social support on risk indicators for cardiovascular disease (CVD) in
165 female nurses. Job strain was measured with the Job Content Questionnaire;
CVD risk was measured with insulin, total cholesterol, triglyceride (TG), high
density lipoprotein cholesterol (HDL-C), fibrinogen, tissue-type plasminogen
activator (tPA) antigen, tPA activity, plasminogen activator inhibitor-1 antigen,
and blood pressure. Multivariate analysis of covariance and regression analyses
revealed no effects of either job strain or social support on these risk
indicators. All risk indicators deteriorated with age and body mass index. Oral
contraceptive use improved fibrinolytic potential and increased HDL-C but had
adverse effects on TG levels. Results suggest that in healthy young women job
strain is not associated with an unfavorable metabolic or fibrinolytic risk
profile.
PMID- 11007152
TI - Psychological response styles and cardiovascular health: confound or independent
risk factor?
AB - Using results from 2 large cardiovascular studies, the authors examined the
utility of treating psychological response styles as confounds (e.g., factors
undermining relationships with other self-report variables) versus distinct
personality traits in the prediction of cardiovascular health. Study 1 consisted
of a 3-year prospective study of ambulatory blood pressure levels in healthy
adults (N = 125). Study 2 comprised a 12-week drug treatment program for ischemic
heart disease patients (N = 95). Participants completed measures of psychological
factors and self-deception and impression management in each study. Results
consistently favored using response styles as direct predictors. Self-deception
scores predicted elevated 3-year diastolic and systolic blood pressure changes in
Study 1 and poorer treatment outcomes in Study 2. Statistically controlling for
response style effects within the psychological factors generally did not improve
predictions. These findings argue against the conceptualization of response
styles as stylistic confounds.
PMID- 11007153
TI - Motivation and dietary self-care in adults with diabetes: are self-efficacy and
autonomous self-regulation complementary or competing constructs?
AB - This study examined constructs drawn from social-cognitive theory (A. Bandura,
1986) and self-determination theory (E. L. Deci & R. M. Ryan, 1985, 1991) in
relation to dietary self-care and life satisfaction among 638 individuals with
diabetes. A motivational model of diabetes dietary self-care was proposed, which
postulates direct links between self-efficacy/autonomous self-regulation, and
adherence/ life satisfaction. Structural equation modeling showed that both self
efficacy and autonomous self-regulation were associated with adherence (betas =
.54 and .21, respectively) and with life satisfaction (betas = .15 and .34,
respectively). Constraint analyses confirmed that self-efficacy was significantly
more associated with adherence, whereas autonomous self-regulation was
significantly more associated with life satisfaction. According to the model,
interventions for dietary self-care and life satisfaction should focus on
increasing self-efficacy and autonomous self-regulation.
PMID- 11007154
TI - Structure of outcome beliefs in condom use. The Project RESPECT Study Group.
AB - To study the structure of beliefs about condom use outcomes, the authors derived
and tested 4 psychosocial hypothetical models: (a) a 2-factor model of the
personal and social outcomes of condom use; (b) a 2-factor model of the pros and
cons of the behavior; (c) a 3-factor model (i.e., physical, self-evaluative, and
social) of outcome expectancies; and (d) a thematic 4-factor model of the
protection, self-concept, pleasure, and interaction implications of the behavior.
All 4 models were studied with a confirmatory factor analysis approach in a
multisite study of 4,638 participants, and the thematic solution was consistently
the most plausible. Self-concept and pleasure were most strongly associated with
attitudes toward using condoms, intentions to use condoms, and actual condom use,
whereas protection and interaction generally had little influence.
PMID- 11007155
TI - A psychosocial model of sun protection and sunbathing in young women: the impact
of health beliefs, attitudes, norms, and self-efficacy for sun protection.
AB - A psychosocial model of sun protection and sunbathing as distinct behaviors was
developed on 202 young Caucasian women and replicated in an independent sample (n
= 207). Proximal outcomes were intention to sun protect and intention to
sunbathe; distal outcomes included sun protection and sunbathing behavior
measured 5 months later. Objective risk for skin cancer plus 4 classes of
psychosocial variables (sun-protective health beliefs, self-efficacy for sun
protection, attitudes toward sunbathing, and norms for sunbathing and sun
protection) served as predictors. Sun-protective norms and self-efficacy for sun
protection predicted only intention to sun protect; sunbathing norms predicted
only intention to sunbathe. Susceptibility and advantages of tanning predicted
both intention constructs, which, in turn, predicted behavior. These findings
distinguish sun protection from sunbathing and provide a basis for intervention
design.
PMID- 11007156
TI - Social-cognitive determinants of nutrition behavior among supermarket food
shoppers: a structural equation analysis.
AB - A social-cognitive model of nutrition behavior (A. Bandura, 1997) was tested
using structural equation modeling of data from 307 food shoppers recruited from
5 supermarkets in Southwest Virginia. The shoppers were participating in the
baseline phase of an ongoing nutrition promotion program. As part of the
evaluation, data were collected on the self-efficacy and outcome-expectations
components of social-cognitive theory as well as on food purchases and intake.
The structural analyses presented here support the social-cognitive model. Self
efficacy, physical outcome expectations, age, socioeconomic status, and number of
children were important predictors of nutrition behavior among shoppers.
Implications for interventions using social-cognitive variables to improve the
nutritional content of food purchases and intake are discussed.
PMID- 11007157
TI - Social-cognitive predictors of health behavior: action self-efficacy and coping
self-efficacy.
AB - The effects of social-cognitive variables on preventive nutrition and behavioral
intentions were studied in 580 adults at 2 points in time. The authors
hypothesized that optimistic self-beliefs operate in 2 phases and made a
distinction between action self-efficacy (preintention) and coping self-efficacy
(postintention). Risk perceptions, outcome expectancies, and action self-efficacy
were specified as predictors of the intention at Wave 1. Behavioral intention and
coping self-efficacy served as mediators linking the 3 predictors with low-fat
and high-fiber dietary intake 6 months later at Wave 2. Covariance structure
analysis yielded a good model fit for the total sample and 6 subsamples created
by a median split of 3 moderators: gender, age, and body weight. Parameter
estimates differed between samples; the importance of perceived self-efficacy
increased with age and weight.
PMID- 11007158
TI - Conscientiousness, perceived risk, and risk-reduction behaviors: a preliminary
study.
AB - Participants (N = 343) from an Oregon community completed surveys at baseline, 3
months, and 12 months to assess personality, the perceived health risk of radon
in combination with smoking, and changes in smoking behavior. Conscientiousness
predicted instituting a more restrictive household smoking rule (p < .01), and
perceived risk predicted reduction in cigarettes smoked per day for men (p <
.001). Perceived risk predicted a reduction in the proportion of cigarettes
smoked in the home for those who had high (p < .05) but not low or moderate
levels of Conscientiousness, a dimension in one personality model. The results
demonstrate the importance of Conscientiousness in the prediction of health
behavior, particularly behavior that affects others as well as oneself.
PMID- 11007159
TI - Hypomethylation of the retrotransposon LINE-1 in malignancy.
PMID- 11007160
TI - Levels of beta-human chorionic gonadotropin in cerebrospinal fluid of patients
with malignant germ cell tumor can be used to detect early recurrence and monitor
the response to treatment.
AB - BACKGROUND: Tumor marker-producing germ cell tumors of the central nervous system
are malignant and require radiation and/or chemotherapy. Although serum beta
human chorionic gonadotropin (hCG) has been used to monitor the course of
treatment, the levels of beta-hCG in the cerebrospinal fluid (CSF) have not been
measured routinely in the clinic. To determine whether they can be used to
evaluate parameters of tumor status, such as progression or response to therapy,
levels of beta-hCG in the serum and CSF of patients with germ cell tumors were
studied. METHODS: Fifty-four paired samples of CSF and serum were taken from
seven patients with germ cell tumor and their beta-hCG levels were measured. Beta
hCG was negative in both serum and CSF in 11 instances and the levels in the
other 43 paired samples were analyzed for any correlation or relationship to
therapy. They were also compared with the clinical courses. RESULTS: The mean CSF
beta-hCG level was 11.5 mIU/ml, which was significantly higher than the level in
serum (3.5, p = 0.002). In all the paired samples except for one time point, the
level in CSF was higher than that in serum. Out of 43 instances where the beta
hCG level in CSF was elevated, the level in serum was elevated in only 16
(37.2%). Among cases of recurrent malignant germ cell tumor, there were nine
instances of recurrence or progression despite therapy. In all five instances
where beta-hCG CSF levels were measured, the levels were elevated prior to any
increase or detectability of the serum values. CONCLUSION: It seems likely that
the level of beta-hCG in CSF is a good marker for monitoring tumor recurrence or
evaluation of treatment results.
PMID- 11007161
TI - Heterogeneous response patterns of alveolar macrophages from patients with lung
cancer by stimulation with interferon-gamma.
AB - BACKGROUND: Macrophages are considered to play an important role in the host
defense against malignant tumors. In this study, cytotoxic activity of alveolar
macrophages (AM) derived from 32 patients with lung cancer was investigated.
METHODS: AM were aseptically obtained by lavage from resected lung and
subsequently tested for cytolytic activity against QG56, a lung squamous cell
line, following treatment with recombinant interferon-gamma (IFN-gamma). RESULTS:
In seven patients (21.9%), AM showed no cytotoxicity even though AM were
incubated with IFN-gamma. In 20 (62.5%), AM showed substantial cytotoxicity in
response to IFN-gamma in a dose-dependent manner. In the other five (15.6%),
relatively strong cytotoxicity was observed even without preincubation with IFN
gamma. Such a heterogeneous profile of the cytotoxicity of AM might be a
reflection of various activated states of AM since the potential of cytotoxicity
and that of IL-1 secretion were almost parallel. Both IFN-gamma dependent and
independent cytotoxicity were partially blocked either by anti-tumor necrosis
factor-alpha (TNF-alpha) antibody or by the inhibitor of nitric oxide synthesis.
However, those activities were completely abrogated by both treatments. Since the
supernatant of AM culture exhibited TNF-alpha-mediated but not NO-mediated
cytolysis, TNF-alpha could mediate a bystander killing whereas NO acts in close
contact with tumor cells. CONCLUSION: The AM have anti-tumor cytotoxicity in lung
cancer although the cytolytic potential is heterogeneous and that the tumor lysis
by AM is mediated by both TNF-alpha and NO production.
PMID- 11007162
TI - Characterization of intracellular cytokine profile of CD4(+) T cells in
peripheral blood and tumor-draining lymph nodes of patients with gastrointestinal
cancer.
AB - BACKGROUND: Analysis of serum cytokine levels has shown that cancer-bearing hosts
have lower levels of IL-2 and IFN-gamma, suggesting that Th1-type immunity is
impaired by cancer. However, the mechanisms of the Th1 dysfunction are not
clearly understood. METHOD: The frequencies of Th1 cells in CD4(+) helper T cells
were evaluated with an intracytoplasmic cytokine staining method in peripheral
blood lymphocytes (PBL) and lymph node lymphocytes (LNL) of patients with
gastrointestinal cancer. RESULTS: Activation of lymphocytes with PMA + Ionomycin
induced the expression of IL-2 and IFN-gamma in each lymphocyte population.
Compared with PBL of non-malignant donors, PBL in cancer patients contained
significantly lower frequencies of CD4(+) T cells that produced IL-2 and IFN
gamma. LNL in cancer patients also contained lower levels of IL-2- and IFN-gamma
producing CD4(+) T cells, although the percentages did not show significant
differences from those of PBL in the same patients. CONCLUSION: Our data suggest
that suppression of Th1 cytokine in cancer patients is, at least in part, due to
the decreased frequency of Th1 cells with CD4(+) phenotype.
PMID- 11007163
TI - Hypomethylation of LINE1 retrotransposon in human hepatocellular carcinomas, but
not in surrounding liver cirrhosis.
AB - BACKGROUND: Cytosine methylation of LINE1 (L1) elements, some of which are
capable of retrotransposition in human cells, is known to play important roles in
transcriptional repression of these retrotransposons. We have previously
identified consistent hypomethylation of L1 elements in mouse liver tumors by a
genome-wide search technique for aberrant methylations. In this study, we
analyzed the methylation status of the L1 elements in human hepatocellular
carcinomas (HCCs). METHODS: Nine pairs of an HCC and its surrounding tissue were
obtained from clinical cases. Genomic DNA was digested with HpaII, a methylation
sensitive restriction enzyme, and hybridized with a probe derived from the
promoter region of the L1 elements. RESULTS: Hypomethylation of the L1 elements
was detected in eight of the nine HCCs, but never in the surrounding liver
tissues, whether or not liver cirrhosis was present. CONCLUSION: Specific
occurrence of the hypomethylation of the L1 elements in the HCCs indicated its
diagnostic value for malignancy. The hypomethylation could also lead to increased
incidence of retrotransposition and resultant genomic instability in HCCs.
PMID- 11007164
TI - Essential thrombocythemia transformed to acute myelogenous leukemia with
t(3;17)(p24; q12), del(5)(q13q34) after treatment with carboquone and
hydroxyurea.
AB - In 1991, a 52-year-old woman was diagnosed as having essential thrombocythemia
(ET). She was doing well with continuous medication with carboquone (CQ) and
subsequently hydroxyurea (HU). However, substantial leukocytosis with leukemic
blast cells, anemia and thrombocytopenia developed in 1996. Analysis of
peripheral blood showed 4.4 x 10(3)/microl white blood cells with 82% of leukemic
blast cells. These blasts showed negative staining with myeloperoxidase by
immunostaining, but the myeloperoxidase was positive by electron microscopic
analysis. Cytogenetic analysis of bone marrow cells revealed a t(3;17)(p24; q12),
del(5)(q13q34). On the basis of these findings, the leukemic blast cells were
classified as acute myelogenous leukemia (AML:M0) in the FAB classification. The
causative agent, CQ and HU in secondary leukemia from ET and chromosomal
abnormality related to ET blastic crisis (BC) are discussed.
PMID- 11007165
TI - Primary extracranial meningioma of the foot: a case report.
AB - We present a rare case of primary extracranial meningioma in a 36-year-old man,
who had a solitary multinodular mass located in the plantar muscle of the foot.
The histology of specimens from simple excision was typical of meningioma,
showing bland spindle cell proliferation with a whorl pattern.
Immunohistochemical analysis demonstrated that the tumor cells showed diffuse and
strong positivity for epithelial membrane antigen as well as moderate reactivity
for cytokeratin and vimentin. Ultrastructurally, the tumor cells were
characterized by thin bipolar cytoplasmic processes and joined by multiple small
desmosomes. There were frequent pinocytotic vesicles and a distinct external
lamina on the cell surface. These findings suggest that this primary ectopic
meningioma, arising in the soft tissue, may have been derived from perineurial
cells of the peripheral nerve, but was morphologically distinguishable from
perineurioma. Primary extracranial meningioma should be included in the
differential diagnosis of soft-tissue spindle cell tumors, especially those of
peripheral nerve origin.
PMID- 11007166
TI - Cancer incidence and incidence rates in Japan in 1995: estimates based on data
from nine population-based cancer registries. The Research Group for Population
based Cancer Registration in Japan.
PMID- 11007167
TI - Report of the Thirteenth International Symposium of the Foundation for Promotion
of Cancer Research: cancer screening-past, present and future.
PMID- 11007168
TI - Cancer statistics digest. Pancreas cancer mortality rates by prefectures in
Japan.
PMID- 11007169
TI - Nutrition and energetics of the canary (Serinus canarius).
AB - Canaries appear to be primarily seed-eaters, although there are no reports of
their feeding ecology in the wild. In captivity, they are offered seed-based
diets, preferring to consume seeds such as canary, rapeseed and millet. The mean
daily dry-matter intake ranges from 3 to 4 g, which corresponds to a mean gross
energy intake of approximately 70 kJ per bird per day. The efficiency of dietary
metabolism is high (0.85), which equates to individual metabolizable energy
intakes of 45-75 kJ per bird per day. For a canary of average body weight (22 g)
the data can be fitted to a regression equation to predict a requirement of 62 kJ
ME per day. This corresponds to published information on the energy requirements
of other passerine species, but deviates from the predictive equation for
poultry. The digestibility values for protein, fat and carbohydrate are similar
to those obtained for the budgerigar, although it is likely that the
digestibility coefficient is dependent upon the seed type and alimentary tract
lipase and amylase activities. Nutrient requirements of canary chicks have not
yet been determined, although recent studies have provided data on the nutrient
intakes of developing chicks. The newly-hatched canary chick has a rapid growth
rate, achieving 90% of its asymptotic body mass by 11 days of age. Gross energy
intake is approximately 3 kJ per day following hatching and by day 10 is
equivalent to that of an adult canary. It appears that the protein intake should
lie between 16.5 and 21.9% of the diet (as is), with peak intake occurring
between 8 and 10 days of age.
PMID- 11007170
TI - Kinetic characterization of outer-ring deiodinase activity (ORD) in the liver,
gill and retina of the killifish Fundulus heteroclitus.
AB - Conversion of T4 to T3 is the first step in TH action and deiodinases are the
major determinants of TH tissue availability and disposal. We here report the
kinetic characterization of the outer-ring deiodinating (ORD) enzymes in the
liver, gill and retina of sea water-adapted killifish, by using both rT3 and T4
as substrates. In liver, by using rT3, we detected a high Km (84 nM) and a low Km
(1.3 nM) component with kinetic characteristics similar to mammalian deiodinases
DI and DII. In contrast, T4-ORD only generated a low Km (0.5 nM) component. As
judged by its Vmax (920 fmol 125I/mg per h) this DII enzyme is very abundant,
approximately five and 20 times higher than that found in trout liver and
hypothyroid rat, respectively. Kinetic analysis in killifish gill showed only one
enzymatic component, with a high rT3 Km (430 nM) and a relatively low Vmax (4.3
pmol 125I/mg per h). Our results in killifish retina show the expression of a T4
low Km (0.6 nM) deiodinase with high cofactor requirements akin to the mammalian
DII. The Vmax value for this enzyme is 182 fmol 125I/mg per h, five times lower
than the one found in killifish liver, but comparable to that in hypothyroid rat
pituitary. The biochemical similarities between fish and mammalian deiodinases
could reflect their high conservation during vertebrate evolution and thus their
importance in the regulation of thyroid hormone action.
PMID- 11007171
TI - Expression of porcine adipocyte transcripts during differentiation in vitro and
in vivo.
AB - Transcript concentrations for the transcription factors, CCAAT enhancer binding
protein beta and alpha (C/EBPbeta and C/EBPalpha), plus the adipocyte
characteristic proteins, fatty acid synthase (FAS), glucose transporter 4 (Glut
4), hormone-sensitive lipase (HSL), insulin receptor (InsR), lipoprotein lipase
(LPL), and leptin were measured during differentiation of porcine stromal
vascular (S/V) cells in vitro. These same transcripts, excluding FAS and InsR,
were measured in porcine adipose tissue from birth to 7 weeks of age. In S/V
cells, C/EBPbeta and InsR were continuously elevated. At day 0, C/EBPalpha was
approximately 20% of the day 9 value. The LPL increased gradually from day 0 to
9, whereas most other transcripts had a lag period of several days. In tissue,
C/EBPbeta was substantial at birth and increased gradually. The C/EBPalpha was
relatively low at birth and increased at day 17. The LPL and leptin increased
continuously. The Glut 4 was low at birth and increased at day 28. The HSL was
relatively low at birth, increased at day 10, and plateaued at day 28.
Transcripts in porcine S/V cells develop somewhat differently from adipocyte
differentiation models established in clonal cells, but the porcine cells
represent a model that should be more applicable to pigs.
PMID- 11007172
TI - Characterization of (Na+, K+)-ATPase in gill microsomes of the freshwater shrimp
Macrobrachium olfersii.
AB - To better understand the adaptive strategies that led to freshwater invasion by
hyper-regulating Crustacea, we prepared a microsomal (Na+, K+)-ATPase by
differential centrifugation of a gill homogenate from the freshwater shrimp
Macrobrachium olfersii. Sucrose gradient centrifugation revealed a light fraction
containing most of the (Na+, K+)-ATPase activity, contaminated with other
ATPases, and a heavy fraction containing negligible (Na+, K+)-ATPase activity.
Western blotting showed that M. olfersii gill contains a single alpha-subunit
isoform of about 110 kDa. The (Na+, K+)-ATPase hydrolyzed ATP with Michaelis
Menten kinetics with K5, = 165+/-5 microM and Vmax = 686.1+/-24.7 U mg(-1).
Stimulation by potassium (K0.5 = 2.4+/-0.1 mM) and magnesium ions (K0.5 = 0.76+/
0.03 mM) also obeyed Michaelis-Menten kinetics, while that by sodium ions (K0.5 =
6.0+/-0.2 mM) exhibited site site interactions (n = 1.6). Ouabain (K0.5 = 61.6+/
2.8 microM) and vanadate (K0.5 = 3.2+/-0.1 microM) inhibited up to 70% of the
total ATPase activity, while thapsigargin and ethacrynic acid did not affect
activity. The remaining 30% activity was inhibited by oligomycin, sodium azide
and bafilomycin A. These data suggest that the (Na+, K+)-ATPase corresponds to
about 70% of the total ATPase activity; the remaining 30%, i.e. the ouabain
insensitive ATPase activity, apparently correspond to F0F1- and V-ATPases, but
not Ca-stimulated and Na- or K-stimulated ATPases. The data confirm the recent
invasion of the freshwater biotope by M. olfersii and suggest that (Na+, K+)
ATPase activity may be regulated by the Na+ concentration of the external medium.
PMID- 11007173
TI - Trypsin-like enzymes from two morphotypes of the 'living fossil' Triops
(Crustacea: Branchiopoda: Notostraca).
AB - Trypsin-like enzymes from two morphotypes (here called short and long) of the
'living fossil' Triops of Baja California Sur, Mexico were studied. Adults of
both morphotypes were obtained from outdoor static cultures using dry soil from
the natural habitats as a source of cysts and culture substrate. Individual and
pooled extracts were made from dissected digestive tubes. The effect of pH and
temperature on the trypsin activity was studied using N-alpha-benzoyl-DL-Arg-p
nitroanilide (BAPNA) as substrate. The highest proteolytic activity was found at
the same pH with extracts of both morphotypes. At this pH, there was greater
proteolytic activity at a lower temperature with the short morphotype extract
than with the long morphotype extract. Substrate-SDS-PAGE zymograms showed bands
of activity. Short morphotype extracts produced six bands; five of them were
serine proteases of which three were trypsin-like enzymes. Long morphotype
extracts revealed eight bands; six of them were serine proteases of which three
were trypsin-like enzymes.
PMID- 11007174
TI - Characterization of the MTF-1 transcription factor from zebrafish and trout
cells.
AB - The metal response element (MRE)-binding transcription factor-1, MTF-1, is a zinc
responsive protein that controls transcription of metallothionein (MT) genes in
many cell types. In addition, MTF-1 is also hypothesized to regulate
transcription of a battery of genes involved in the defense against oxidative
stress. Manipulating the Zn concentration in the low microM range reversibly
modulates the DNA-binding activity of the mammalian MTF-1; this effect is
inhibited at low temperature. This report examines the presence and binding
properties of MTF-1 in cell lines derived from warm- and cold-water fishes
(zebrafish and trout, respectively). We found that both species of fish express
MRE-specific binding activities that are immunologically similar to mouse MTF-1.
MTF-1-binding from the cells of both species of fish was activated when cells
were treated with Zn but not with Cd. Zebrafish cells contained a single isoform
of MTF-1 with binding properties similar to mammalian MTF-1. Trout cells, on the
other hand, contained two isoforms of MTF-1: MTF-1H and MTF-1L. Zn reversibly
modulated MTF-1H binding in a temperature-dependent manner. Similarly, Zn
reversibly modulated MTF-1L binding, but, in contrast, such modulation occurred
readily at 4 degrees C. This data demonstrate the conservation of binding
specificity, binding properties, and regulation of MTF-1 in fishes.
PMID- 11007175
TI - Properties of lactate dehydrogenase from the isopod, Saduria entomon.
AB - Saduria entomon lactate dehydrogenase (LDH-A4*) from thorax muscle was purified
about 89 fold to specific activity 510 micromol NADH/min/mg using Cibacron Blue
3GA Agarose and Oxamate-Agarose chromatographies. The enzyme is a tetramer, with
molecular weight of 140 kDa for the native enzyme and 36 kDa for the subunit. The
isoelectric point was at pH 5.7. The enzyme possesses high heat stability (T50 =
71.5 degrees C). The optimum pH for pyruvate reduction reaction was 6.5, while
for lactate oxidation one, the maximum activity was at pH 9.1. The Km for
pyruvate was minimal at 5 degrees C, the average environmental temperature of the
isopod. The Km values determined at 30 degrees C and optimal pH for pyruvate
reduction and lactate oxidation were 0.18 and 90.04 mM, respectively. Amino acid
compositional analyses showed the strongest resemblance of the isopod isoenzyme
to cod (Gadus morhua) LDH-C4.
PMID- 11007176
TI - Astaxanthin is the major carotenoid in tissues of white storks (Ciconia ciconia)
feeding on introduced crayfish (Procambarus clarkii).
AB - We studied the carotenoid pigments in plasma, skin and body fat of white storks
(Ciconia ciconia) from a colony in Spain feeding mainly on the recently
introduced red swamp crayfish (Procambarus clarkii). In control colonies, where
crayfish was absent, plasma was collected for comparison. Our objective was to
determine whether the astaxanthin contained in the crayfish reached the blood,
accumulated in fat, and finally was deposited in the red-colored bill and legs.
If that was true, the visual cues provided by those tegumentary areas would be
altered, with potential behavioral consequences. Plasma carotenoids were directly
extracted with acetone, whereas skin and fat samples needed harsher conditions,
i.e. grinding, sonication and extraction with diethyl ether. The extracts were
analyzed by thin-layer chromatography (TLC) and UV/Vis spectroscopy. In crayfish
eating storks, astaxanthin was confirmed to be the dominant pigment in all
analyzed tissues. This red pigment was absorbed unchanged in the gut, and was
responsible for the red color of plasma and the abnormal orange pigmentation of
the feather-covered skin. It was also present in large quantities in the exposed
bill and tarsi, which are typically red-colored in the stork. Control storks with
no crayfish in the diet only presented lutein in their plasma.
PMID- 11007177
TI - Effects of rabbit gastrointestinal mucins and dextran on hydrochloride diffusion
in vitro.
AB - We compared a viscous fingering formation of hydrochloric acid (HCl) in rabbit
corpus, antral and duodenal mucins and with dextran under neutral and acidic
conditions with respect to relative viscosity, molecular mass, and carbohydrate
composition. The effect of desialyzation of duodenal mucin on the viscous
fingering formation of HCl was also examined. HCl (0.1 N) was injected into 1%
solutions of mucins and dextran and a subsequent viscous fingering formation was
assessed based on an influx volume rate of HCl. A low influx volume rate
indicates a high ability of the solutions to produce viscous fingers. The influx
volume rate of HCl was lowest in duodenal mucin followed bl corpus mucin, antral
mucin, and dextran at pH 7. The influx volume rate of HCl was inversely
correlated with the relative viscosity of the solution. Maximum molecular masses
were large in the order of corpus, antral, and duodenal mucins, and they were
larger than dextran T2000. Rabbit gastrointestinal mucins were very polydisperse
system. Duodenal mucin contains more sialic acid than gastric mucins; the influx
volume rate of HCl increased in desialylated duodenal mucin. It is suggested that
the higher ability of gastric mucins to prevent HCl diffusion than dextran were
due to the differences in the molecular mass. The ability of duodenal mucin to
prevent HCl diffusion was probably attributed to its high sialic acid content,
which may reflect a physiological role of duodenal mucin in the duodenum that has
to deal with HCl influx from the stomach.
PMID- 11007178
TI - Oxygen transport proteins: III. Structural studies of the scorpion (Buthus
sindicus) hemocyanin, partial primary structure of its subunit Bsin1.
AB - The hemocyanin (Hc) from Buthus sindicus, studied in the native state,
demonstrated to be an aggregate of eight different types of subunits arranged in
four cubic hexamers. Both, the 'top' and the 'side' views of the native molecule
have been identified from the negatively stained specimens using transmission
electron microscopy. Out of these, eight different polypeptide chains, the
partial primary structure (68%) of a subunit Bsin1 (Mr = 72422.7 Da) was
established using a combination of automated Edman degradation and mass
spectrometry. A multiple sequence alignment with other closely related
cheliceratan Hc subunits revealed average identities of ca. 60%. Most of the
structurally important residues, i.e. copper and calcium-binding ligands, as well
as the residues involved in the presumed oxygen entrance pathway, proved to be
strictly conserved in Bsin1. Sequence variations have been observed around the
functionally important chloride-binding site, not only for the B. sindicus
subunit Bsin1, but also for the subunit Aaus-6 of the scorpion A. australis and
the subunit Ecal-a from the spider Eurypelma californicum Hcs. Deviation in the
primary structure related to the chloride-binding site suggest that the effect of
chloride ions may vary in different hemocyanins. Furthermore, the secondary
structural contents of the Hc subunit Bsin1 were determined by circular dichroism
revealing ca. 33% alpha-helix, 18%, beta-sheet, 19% beta-turn, and 30% random
coil composition. These values are in good agreement with the crystal structure
of the closely related Hc subunit Lpol-II from horseshoe crab L. polyphemus.
Electron microscopic studies of the purified Hc subunit under native conditions
revealed that Bsin1 has self aggregation properties. Results of these studies are
discussed.
PMID- 11007179
TI - Cross-reactivities of polyclonal antibodies against factor V activating enzyme, a
serine proteinase from Vipera lebetina (snake) venom.
AB - Antibodies to the factor V activating enzyme from Vipera lebetina venom were
produced by immunizing a rabbit with chromatographically purified factor V
activating enzyme probes. The antibodies cross-reacted with different protein
fractions in 23 snake venoms (ten viperid, eight crotalid, and five elapid
venoms) as demonstrated by western immunoblotting. In the venom of Vipera
russelli the antibodies recognized only one protein band which probably belonged
to factor V activating enzyme.
PMID- 11007180
TI - In vitro polymerization of mussel polyphenolic proteins catalyzed by mushroom
tyrosinase.
AB - The in vitro enzymatic polymerization of the polyphenolic protein purified from
the mussels Aulacomya ater, Mytilus edulis chilensis and Choromytilus chorus was
studied. Mushroom tyrosinase was used to oxidize the dopa residues present in
these proteins, and polymerization was monitored by acid-urea polyacrylamide gel
electrophoresis. The protein from A. ater polymerized at a faster rate than the
other two. Amino acid analysis of the crosslinked protein showed a notable
decrease in the content of dopa, but no significant change of other amino acids.
This suggests that crosslink formation may be limited to the oxidized dopa
derivatives of the protein molecules.
PMID- 11007181
TI - Metabolites from a marine bacterium Pseudomonas/Alteromonas, associated with the
sponge Dysidea fragilis.
AB - The lipophylic extract from a Black Sea bacterium, associated with the sponge
Dysidea fragilis, was investigated. Saturated hydrocarbons and fatty acids of the
lipids were identified. The concentrations of the polycyclic compounds appeared
to be negligible. The main components appeared to be phosphatidyl ethanolamine,
followed by phosphatidyl serine. The first was investigated by FAB mass
spectrometry and a series of molecular species partially identified.
PMID- 11007182
TI - Partial characterization of vitellin and localization of vitellogenin production
in the terrestrial isopod, Armadillidium vulgare.
AB - Vitellins were purified separately from ovaries and eggs of the isopod,
Armadillidium vulgare. Ovarian vitellin consisted of at least six proteins with
relative molecular masses of 205, 200, 185, 180, 122 and 112 kDa. The larger four
proteins disappeared in eggs within a week after oviposition and a 59-kDa protein
appeared thereafter. The amino-terminal amino acid sequences of these vitellin
proteins were identical except for the ovarian 112 kDa, egg 112 kDa and 59 kDa
proteins, and showed considerable similarity to those of known vitellogenins from
other animals. Comparison of tryptic peptide maps of the 122 and 112 kDa proteins
from eggs on reversed-phase HPLC and sequence identification of two randomly
selected peaks having the same retention times indicated that two peptides were
mostly similar in sequence. PCR-assisted cloning of the 5' region of a cDNA (591
bp) encoding vitellogenin revealed the presence of a signal peptide consisting of
16 amino acid residues and clarified the structural relationship among the
protein components except for the ovarian 112 kDa and the egg 59 kDa proteins.
Northern blot analysis revealed that the fat body is the main vitellogenin
producing organ.
PMID- 11007183
TI - Succinate and alanine as anaerobic end-products in the diving turtle (Chrysemys
picta bellii).
AB - The western painted turtle is an extremely anoxia-tolerant vertebrate capable of
tolerating blood lactate levels of 150-200 mM. Since lactate increases to such
high levels, other fermentation end-products such as succinate and alanine, which
have not been previously measured in this species, might also be expected to
increase. Therefore, I measured turtle heart, liver, and blood concentrations of
lactate, succinate, and alanine following a 28-day anoxic dive at 5 degrees C.
Succinate and lactate concentrations increased significantly in all three
compartments while alanine increased significantly in the liver only. Lactate was
found to accumulate by a similar amount in all three compartments (66.4-80.5
micromol g or ml(-1) in the blood compartment) and was used as a reference to
which alanine and succinate concentrations could be compared. Succinate and
alanine levels increased by 2 and 0.9% of lactate in liver, approximately 0.3 and
0.04% of lactate in blood, and 0.6 and 0.07% of lactate in heart, respectively.
The contribution of each to the total anoxic heat production was calculated and
accounted for an additional 1.5% of the previously measured exothermic gap. I
conclude that succinate and alanine concentrations do increase in the anoxic
turtle but are minor anaerobic end-products.
PMID- 11007184
TI - Differential expression of sialic acid on porcine organs during the maturation
process.
AB - Sialylated structures play important roles in cell communication, and change in a
regulated manner during development and differentiation. In this work, we report
the main glycosidic modifications that occur during the maturation of porcine
tissues, involving the sialylation process as determined with lectins. Sialic
acids were identified at several levels in a broad range of cell types of
nervous, respiratory, genitourinary and lymphoid origin. Nevertheless, the most
contrasting was the type of glycosidic linkage between 5-N-acetyl-neuraminic acid
(Neu5Ac) and galactose (Gal) expressed in central nervous system (CNS). Newborn
CNS abundantly expressed Neu5Acalpha2,3Gal, but weakly or scarcely expressed
Neu5Acalpha2,6Gal/GalNAc. Maturation of CNS induced drastic changes in sialic
acid expression. These changes include decrease or complete loss of
NeuAcalpha2,3Gal residues, mainly in olfactory structures and brain cortex, which
were replaced by their isomers Neu5Acalpha2,6Gal/GalNAc. In the brain cortex and
cerebellum, the increase of Neu5Acalpha2,6Gal/GalNAc molecules was paralleled by
an increase of 5-N-acetyl-9-O-acetyl-neuraminic acid (Neu5,9Ac2). In addition,
terminal Gal and N-acetyl-D-galactosamine (GalNAc) residues also increased their
expression in adult CNS tissues, but this was more significant in structures
forming the encephalic trunk. Our results show that sialylation of porcine CNS is
finely modulated throughout the maturation process.
PMID- 11007185
TI - Digestive amylase from the larger grain borer, Prostephanus truncatus Horn.
AB - A combination of ion-exchange chromatography, preparative electrophoresis and gel
filtration chromatography allowed a 1209-fold purification of one of the two
major digestive alpha-amylases from larvae of the larger grain borer,
Prostephanus truncatus Horn. The purified enzyme showed a molecular mass of 60.2
kDa, an isoelectric point of 4.7 and an optimal pH for activity of 6.0. The
enzyme was heat labile and it was recognized by proteinaceous inhibitors from
amaranth seeds (Amaranthus hypochondriacus), whereas extracts from maize (Zea
mays) and tepary bean (Phaseolus acutifolius) produced very low inhibition. When
the enzyme was measured at different stages of development, maximal activity was
found in the second instar larvae. Activity drastically decreased to a very low
level during the pupae stage and increased again at the adult stage. A zymogram
of the different developmental stages showed two main bands of alpha-amylase
activity, which almost disappeared at the pupae stage to increase again during
the adult stage, revealing a new, smaller band. This new band may be required for
a better adaptation of the adult insect to its new environment.
PMID- 11007186
TI - Gene products from LUQ neurons in the abdominal ganglion are present at the renal
pore of Aplysia californica.
AB - The L2-4,6 and L5 cells located in the left upper quadrant of the abdominal
ganglion of Aplysia californica express the L5-67 and LUQ-1 genes, respectively,
in a nonoverlapping manner. These cells send major neurites to the kidney and at
least some of them were shown to innervate the renal pore closer muscle, and
thereby control its function. By using in-situ hybridization and
immunofluorescence, the presence of L5-67 and LUQ-1 mRNAs and peptides was
studied in the kidney, with emphasis on the region of the renal pore. We detected
immunoreactive materials in many small varicose nerve fibers running along the
central epithelium in the inner parts of the kidney, and in neurites located
within a large nerve associated with muscles inside the renal pore. Our
observations represent the first direct evidence of the presence of gene products
from LUQ cells at the renal pore, suggesting that they may be responsible for
mediating LUQ cell signals. Furthermore, mRNAs coding for the L5-67 and LUQ-1
peptides were also found in the nerve structure inside the renal pore. Our report
documents a striking example of neuropeptide mRNA targeting nerve terminals that
are very distant from their cell bodies.
PMID- 11007187
TI - Phosphatidylcholine-specific phospholipase C-mediated induction of phospholipase
D activity in Fas-expressing murine cells.
AB - We have previously reported that Fas cross-linking resulted in the activation of
phosphatidylcholine-specific phospholipase C (PC-PLC) and the subsequent
activation of protein kinase C (PKC) and phospholipase D (PLD) in A20 cells. In
an attempt to correlate the existence of PC-PLC activity and activation of PLD by
Fas activation among various Fas-expressing murine cell lines, we have
investigated the effect of anti-Fas monoclonal antibody on PC-PLC and PLD
activities in A20, P388D1 and YAC-1 cell lines. Upon treatment of anti-Fas
monoclonal antibody to these three cell lines, the activation of PLD was only
observed in A20 cells. When the effect of anti-Fas monoclonal antibody on PKC and
PC-PLC activities in Fas-expressing clones were investigated, the activation of
PKC and PC-PLC was detected only in A20 clones. Results presented here also show
that exogenous addition of Bacillus cereus PC-PLC activates PC hydrolysis, PKC
and PLD in all three murine cell lines. These findings suggest that the
activation of PC-PLC is a necessary requirement for the activation of PLD by Fas
cross-linking and cell lines devoid of functional PC-PLC activity could exhibit
enhanced PLD activity by exogenous addition of PC-PLC.
PMID- 11007188
TI - Introduction to the Margaux Conference on Critical Illness: activation of the
coagulation system in critical illnesses.
PMID- 11007189
TI - Pathophysiologic basis of sepsis: considerations for future strategies of
intervention.
AB - OBJECTIVE: To analyze the implications for therapeutic advances in the treatment
of sepsis and septic shock based on the mechanisms underlying the response to
microbial infection. DATA SOURCES: Clinical trials and experimental models
designed to determine the key mechanisms involved in cellular and molecular
processes of inflammatory reactions. STUDY SELECTION: Analyses of normal immune
reactions to microbial infection, processes involved in the development of
sepsis, and reasons for frequent failure of regimens based on current therapeutic
rationales. DATA EXTRACTION/SYNTHESIS: Review of the data suggests that the
dysregulation of the immune system resulting in sepsis/septic shock is
ineffectually blocked by interfering with the action of inflammatory mediators or
cascades, as these processes may be too complex to be easily antagonized. Rather,
blockade of the action of microbial products or of the intracellular processes
activated by receptor interaction with these products may provide a more
promising therapeutic alternative. CONCLUSIONS: The sepsis syndrome induced by
microbial pathogens reflects excessive stimulation of the processes of innate
immunity. Bacterial components reacting with specific receptors activate
intracellular processes, resulting in the release of excessive amounts of
mediators of inflammation as well as triggering multiple complex proteolytic
cascades. Blockade or antagonism of the actions of individual intermediary
messenger molecules has proved therapeutically unsuccessful, because blockade of
mediators alone does not block the direct activation of processes such as
coagulation and complement. The dysregulation that characterizes sepsis may be
amenable to blockade of the bacterial components or to the intracellular pathways
triggered by these products.
PMID- 11007190
TI - Pathophysiology of disseminated intravascular coagulation in sepsis.
AB - Disseminated intravascular coagulation (DIC) is an acquired syndrome
characterized by intravascular fibrin formation occurring in the course of a
variety of severe diseases. In gram-negative sepsis, endotoxin is the bacterial
component eliciting a cascade of tissue factor dependent hypercoagulable
reactions mediated by cytokines, including tumor necrosis factor-alpha and
interleukin-6. Fibrinolysis is activated in this process by the action of tumor
necrosis factor-alpha, but its activity is impaired by the predominant inhibitory
effect of plasminogen activator inhibitor-1. Natural inhibitory mechanisms
include antithrombin, the protein C system, and tissue factor pathway inhibitor.
Each of these defense systems counteracts the harmful effects of DIC, and its
acquired deficiency is associated with increased mortality in observational
studies. The generation of several proteases in DIC, including factor Xa and
thrombin, has potential interactions with inflammatory pathways that may
potentiate the systemic inflammatory syndrome that often accompanies DIC.
Experimental studies support the notion that defects in the protein C pathway
modulate the inflammatory response, and illustrate that coagulation and
inflammation are coupled systems in DIC.
PMID- 11007192
TI - Novel approaches to the management of disseminated intravascular coagulation.
AB - OBJECTIVE: Disseminated intravascular coagulation (DIC) is a syndrome
characterized by systemic intravascular activation of coagulation, leading to
widespread deposition of fibrin in the circulation. We addressed the issue of
whether there is evidence that this fibrin deposition contributes to multiple
organ failure. We also explored the current knowledge on the pathogenesis of DIC
and reviewed current and future treatment for DIC. DATA SOURCES: We searched and
reviewed published articles on experimental studies of DIC models in animals and
clinical studies in patients with DIC. DATA SYNTHESIS: There is ample
experimental and clinical evidence that DIC contributes to morbidity and
mortality. Recent knowledge on important pathogenetic mechanisms that may lead to
DIC has resulted in novel preventive and therapeutic approaches to patients with
DIC. Although the trigger for the activation of the coagulation system may vary
depending on the underlying condition, it is usually mediated by several
cytokines. Thrombin generation proceeds via the (extrinsic) tissue factor/factor
VIIa route and simultaneously occurring depression of inhibitory mechanisms, such
as antithrombin III and the protein C-protein S system. Also, impaired fibrin
degradation, because of high circulating levels of plasminogen activator
inhibitor, type 1, contributes to enhanced intravascular fibrin deposition.
CONCLUSIONS: Although the cornerstone of DIC management is the specific and
vigorous treatment of the underlying disorder, strategies aimed at inhibiting
coagulation activation may theoretically be justified. Such strategies have been
found to be beneficial in experimental and initial clinical studies. These
strategies, which follow from our current understanding of the pathophysiology of
DIC, involve inhibition of tissue factor-mediated activation of coagulation or
restoration of physiologic anticoagulant pathways by means of the administration
of antithrombin concentrate or (activated) protein C concentrate. Although no
complete evidence from controlled clinical trials is available for most of the
proposed therapeutic interventions, these novel strategies are being studied.
PMID- 11007191
TI - Description of compensated and uncompensated disseminated intravascular
coagulation (DIC) responses (non-overt and overt DIC) in baboon models of
intravenous and intraperitoneal Escherichia coli sepsis and in the human model of
endotoxemia: toward a better definition of DIC.
AB - OBJECTIVE: Work toward a better definition of disseminated intravascular
coagulation (DIC) by characterizing the difference between compensated and
uncompensated responses of the hemostatic system to inflammatory stress in
baboons and human subjects using global coagulation and molecular marker assays
of hemostatic, inflammatory, and endothelial perturbation. DESIGN: We conducted
prospective evaluation of the response of baboons to increasing concentrations of
intravenous Escherichia coli, human subjects to intravenous endotoxin, and
baboons to intraperitoneal E. coli. SETTING: Animal laboratory and medical
intensive care facilities, University of Oklahoma Medical School laboratories.
SUBJECTS: Cynocephalus baboons; normal healthy male human subjects (age, 24-37
yrs). MEASUREMENTS AND MAIN RESULTS: Global coagulation assays, white blood cell
counts, and molecular marker assays (ELISA) of components of the inflammatory and
hemostatic systems, neutrophil release products, and endothelial injury. A fall
in both fibrinogen concentration and platelet counts indicated a decompensated
hemostatic response to inflammatory stress (ie, overt DIC). These responses were
observed 2-6 hrs after intravenous infusion of 10(9) and 10(10) colony-forming
units (CFU)/g of E. coli and after implantation of 10(11) CFU/g of E. coli into
the peritoneal cavity. However, 6 hrs after E. coli challenge, these tests were
much less reliable as markers of overt DIC because the fibrinogen underwent an
acute phase response and the platelet count fell and remained depressed for 48
hrs in the face of a coagulopathic response that was already beginning to
resolve, as reflected by a rising fibrinogen concentration. This lack of
reliability was particularly evident in the E. coli peritonitis studies, in which
one third of the animals recovered, one third remained sick for up to 14 days,
and one third died. In contrast, fibrin degradation products and the molecular
markers thrombin/antithrombin, soluble fibrin monomer, protein C, and activated
protein C/inhibitor complexes responded consistently in a dose-dependent manner
regardless of the length of time after challenge. These variables exhibited this
dose response to 106 and 108 CFU/g of E. coli in absence of a fall in fibrinogen
concentration. This was defined as a compensated hemostatic response to
inflammatory stress (ie, non-overt DIC). The values of these variables correlated
closely with rising concentrations of markers of neutrophil activation
(elastase/alpha 1 antitrypsin) and endothelial injury (soluble thrombomodulin).
This was particularly evident in the human response to endotoxin, in which there
was abundant evidence of hemostatic marker response in absence of a fall in
platelet or fibrinogen concentration, both immediately after endotoxin infusion
(first stage, 0-8 hrs after endotoxin) and later (second stage, 12-48 hrs after
endotoxin). CONCLUSION: Global coagulation tests are most useful in detecting
overt consumptive coagulopathy (overt DIC) near the time of challenge or injury
(1 to 6 hrs). Molecular markers can detect and grade the degree of hemostatic
stress of a non-overt consumptive coagulopathy (nonovert DIC). These markers
correlate with degree of endothelial cell injury and reveal a reperfusion injury
stage (second stage) in the human endotoxin model of compensated hemostatic
stress after all clinical symptoms have subsided and the subjects have returned
to work.
PMID- 11007193
TI - Tissue factor pathway of coagulation in sepsis.
AB - OBJECTIVE: To review the role of the tissue factor pathway of coagulation in
experimental sepsis. DATA SOURCES: Studies published in biomedical journals.
STUDY SELECTION: Studies on the role of the tissue factor pathway in animal or
human models for sepsis. DATA EXTRACTION AND SYNTHESIS: Variables reflecting
tissue factor pathway activation in the various models are discussed; the effects
of administration of tissue factor pathway inhibitors on these and inflammatory
variables, as well as on the course and outcome, are analyzed. CONCLUSION:
Activation of coagulation during experimental sepsis occurs mainly, if not
exclusively, via the tissue factor pathway; inhibitors of this pathway improve
mortality, presumably by a combined attenuating effect on coagulative and
inflammatory responses.
PMID- 11007194
TI - Tissue factor inhibition and clinical trial results of tissue factor pathway
inhibitor in sepsis.
AB - Tissue factor mediated pathways leading to microvascular thromboses and
endothelial activation appear to play an important role in the development of
multiple organ failure associated with severe sepsis. Tissue factor pathway
inhibitor (TFPI) is an endogenous inhibitor of tissue factor associated
coagulation cascades. In experimental models of severe sepsis, treatment with
TFPI results in significant reduction in mortality. Similarly, a recently
completed Phase II 210-patient study comparing placebo and infusions of TFPI
showed trends toward a relative reduction in day 28 all-cause mortality in TFPI
treated patients. These data suggest that coagulation cascades involving tissue
factor contribute to organ dysfunction in critically ill septic patients. TFPI
may be a useful therapy in improving outcome of severe sepsis.
PMID- 11007195
TI - Therapeutic rationale for antithrombin III in sepsis.
AB - OBJECTIVE: To review the preclinical evidence that provides the therapeutic
rationale for antithrombin as a novel treatment for human sepsis. DATA SOURCES: A
summary of published medical literature from MEDLINE search files and other
reviews published about antithrombin use in sepsis. DATA SUMMARY: Antithrombin
has a variety of antiinflammatory properties in addition to its functions as an
endogenous anticoagulant that appear to have an important therapeutic role in the
prevention of microvascular dysfunction and multiple organ injury in sepsis.
Appropriate timing and dosing of antithrombin III is critical to realize its full
therapeutic potential as an anti-sepsis therapy. CONCLUSIONS: Antithrombin is a
potent inhibitor of thrombin-mediated vascular injury in the microcirculation in
severe sepsis. This endogenous anticoagulant is rapidly depleted in the early
phases of sepsis as a result of decreased synthesis, increased destruction, and
enhanced clearance by thrombin-antithrombin complex formation. The therapeutic
efficacy of antithrombin in experimental sepsis is readily demonstrable in
numerous animal systems. Appropriately defined patient populations with early
onset severe sepsis and/or septic shock may benefit from antithrombin therapy if
it is administered in adequate doses at the optimal time interval.
PMID- 11007196
TI - Clinical trial results with antithrombin III in sepsis.
AB - OBJECTIVE: To present and discuss the rationale and results of clinical trials
using antithrombin (AT) supplementation in patients with sepsis. DATA
SOURCES/STUDY SELECTION: Review of all controlled (open or double-blind) studies
of patients with severe sepsis or septic shock who were treated with AT
concentrates to obtain better control of coagulation activation and inflammation.
DATA EXTRACTION: AT is a major inhibitor of the coagulation cascade. Recent
experimental studies have also shown that it can modulate the inflammatory
reactions that occur during sepsis. An early and prolonged decrease in AT
activity is well documented during sepsis-induced disseminated intravascular
coagulation and during the systemic inflammatory response. Thus, supplementation
with AT concentrates has been proposed as a potential therapy in sepsis patients.
DATA SYNTHESIS: Numerous uncontrolled studies of AT supplementation in sepsis
patients have been reported in the last 20 yrs. Since 1993, four placebo
controlled randomized studies have been performed in France, Germany,
Northwestern Europe, and Italy. Three of these studies were subjected to a meta
analysis of 122 patients. Results showed a nonsignificant 22% reduction in the 30
day all-cause mortality and a reduction in the length of stay in the intensive
care unit in the AT treated group. The Italian study of 120 patients demonstrated
that the overall mortality was similar in the placebo and treated groups.
However, post hoc analysis according to the Cox regression model showed that in
patients with septic shock, AT supplementation significantly decreased the risk
of death. CONCLUSIONS: Together, these studies are consistent with the positive
effect seen with AT supplementation in patients with severe sepsis. A multicenter
phase III trial is currently in progress to definitively document its effect on
mortality.
PMID- 11007197
TI - The protein C pathway.
AB - OBJECTIVE: To examine the role of the protein C anticoagulant pathway in the
regulation of microvascular thrombosis. The mechanisms by which inflammation
impairs the function of this pathway are also reviewed; conversely, we will
survey emerging knowledge of the multiple mechanisms by which the protein C
anticoagulant pathway can control the inflammatory response. DATA SOURCES: The
information reviewed here was taken from the primary literature, including recent
abstracts. STUDY SELECTION: All studies that bear directly on the
interrelationship between the protein C anticoagulant pathway and inflammation
were included, as was a summary of the initial clinical experience with protein
C/activated protein C therapy in sepsis. DATA EXTRACTION AND SYNTHESIS: The
results from each of the experimental approaches are summarized. Clinical
experience with protein C supplementation in sepsis, although promising, is still
in the early stages of study. CONCLUSIONS: The protein C anticoagulant pathway is
a major mechanism in controlling microvascular thrombosis. Protein C deficiency
that can occur in sepsis facilitates thrombin generation in the microvasculature,
probably augmenting inflammatory responses and contributing to endothelial cell
dysfunction. Animal studies and preliminary clinical results suggest that protein
C/activated protein C supplementation may be useful in reversing microvascular
dysfunction.
PMID- 11007198
TI - Protein C levels as a prognostic indicator of outcome in sepsis and related
diseases.
AB - OBJECTIVE: To consider the appropriateness of protein C levels as a prognostic
indicator for sepsis and related diseases. DATA SOURCES/STUDY SELECTION:
Published research and review articles related to protein C deficiency in
patients with sepsis and related diseases. DATA EXTRACTION AND SYNTHESIS: All
applicable data were extracted, and relevant literature was cited to support
factual statements in the text. The protein C pathway represents one of the major
regulatory systems of hemostasis, exhibiting antithrombotic, profibrinolytic, and
anti-inflammatory properties. Numerous studies have shown that acquired protein C
deficiency is prevalent in the majority of septic patients (>85%) and is
associated with increased morbidity and mortality in patients with severe sepsis
and septic shock. This deficiency in protein C is not simply a transient marker
for sepsis, but parallels the progress of the disease. In addition, protein C
deficiency occurs in the presence of a wide range of pathogens and develops early
in the disease process. CONCLUSIONS: A review of the relevant literature suggests
that protein C levels may serve as a useful prognostic indicator of outcome in
sepsis and related diseases.
PMID- 11007199
TI - Meningococcemia as a model for testing the hypothesis of antisepsis therapies.
AB - OBJECTIVE: To critically review the advantages and disadvantages of pediatric
meningococcemia as a model for testing antisepsis therapies. DATA SOURCES:
Research and review articles on the pathogenesis and treatment of human
meningococcemia, as well as editorial commentaries discussing the failure of
clinical trials for adult sepsis or Systemic Inflammatory Response Syndrome. Data
from these sources are presented in the context of the author's experience as
principal investigator in a large, randomized trial on children with invasive
meningococcal disease. STUDY SELECTION AND DATA EXTRACTION: Studies were selected
to include aspects of epidemiology, pathophysiology, outcome prediction, and
therapeutic trials. DATA SYNTHESIS: Compared with an adult sepsis population,
meningococcemia is a single disease, diagnosed clinically with high reliability.
Patients are previously healthy, without underlying medical or surgical
conditions. In contrast to sepsis trials, nearly all patients with meningococcal
disease receive effective antibiotics. Finally, meningococcemia most closely
resembles animal models of endotoxin infusion, in which most antisepsis therapies
have been highly effective. However, the meningococcal model carries major
disadvantages, among them that meningococcemia is rare and rapidly progressive
and patients are widely dispersed geographically. In addition, a wide range of
experimental therapies is routinely provided in an attempt to preserve life or
limbs. CONCLUSIONS: Meningococcemia is an ideal model of a rapidly progressive
bacterial infection associated with marked endotoxemia. Problems with the model
can be overcome by extensive pretrial logistic planning, as well as close
coordination and cooperation with national regulatory agencies.
PMID- 11007200
TI - Do new strategies in meningococcemia produce better outcomes?
AB - Meningococcal septic shock (MSS) has high mortality and morbidity rates. In
addition to the traditional prompt antibiotics and respiratory and circulatory
support, new treatment strategies have been proposed. AGAINST THE INFLAMMATORY
CASCADE: Immunotherapy, such as antiserum to Escherichia coli J5 and human
antilipid A monoclonal antibodies/centoxin (HA-1A), did not significantly alter
the mortality rate of MSS; we are awaiting the results of the
bactericidal/permeability-increasing protein multicenter trial. Two series
reported the effects of hemofiltration and hemodiafiltration in MSS, but the true
benefits remain unknown. TO TREAT HEMOSTATIC ABNORMALITIES: In MSS, heparin is
still controversial and antithrombin concentrate use has been reported in only
one child. Several case reports on protein C and recombinant tissue plasminogen
activator have been published; the efficacy (improvement in shock and organ
dysfunction and reduction in amputation rate) and safety (intracerebral
hemorrhage with recombinant tissue plasminogen activator) of these treatments
need further evaluation. Blood and plasma exchange appear to be safe and are
supposed to reduce mortality, but it is difficult to draw firm conclusions from
published studies. Finally, local application of medicinal leeches has been
reported to improve purpuric lesions. TO INDUCE VASODILATION: Prostacyclin, or
epoprostenol, infusion, sodium nitroprussiate infusion, sympathetic blockade, and
topical nitroglycerin have been reported to improve distal perfusion; however,
these reports are all anecdotal. OTHER STRATEGIES: Improvement in limb perfusion
was achieved after hyperbaric oxygenation in patients with purpura fulminans
caused by different pathogens. Most authors recommend monitoring of compartment
pressures and performing fasciotomy as indicated. Finally, extracorporeal
membrane oxygenation was recently proposed to support seven children with
intractable MSS. CONCLUSIONS: There is no proof that unconventional treatments
have a significant impact on outcome in MSS; prospective multicenter trials are
needed. At present, early recognition of meningococcal sepsis and appropriate
treatment seem to be the optimal methods of improving outcome. Efforts to find an
effective meningococcal vaccine must be continued.
PMID- 11007201
TI - Meningococcal disease as a model to evaluate novel anti-sepsis strategies.
AB - OBJECTIVE: To consider the appropriateness of meningococcemia as a clinical
entity for the evaluation of anti-endotoxin agents. DATA SOURCES: English
language published literature concerning meningococcemia, sepsis, and endotoxin.
STUDY SELECTION: The purpose of this work is to consider some of the practical
and scientific issues that arise in designing clinical trials to evaluate anti
endotoxin agents. A selected review of recently published articles was
undertaken. DATA EXTRACTION AND SYNTHESIS: Relevant literature has been cited to
support factual statements in the text. CONCLUSION: Meningococcemia as a paradigm
of endotoxin-mediated Gram-negative sepsis has many advantages. It is a
homogeneous population, and it represents a single, measurable, bacterial target
that is unequivocally implicated in the pathogenesis of the disease. However, it
is an uncommon disease that may develop so quickly that attempts to intervene may
be too late to have an effect. There is considerable morbidity, but how best to
measure the outcome and the extent to which the results can be extrapolated to
adult populations with sepsis secondary to nosocomial infection remain unclear.
PMID- 11007202
TI - Coagulation inhibitor replacement in sepsis is a potentially useful clinical
approach.
AB - In sepsis, levels of the endogenous coagulation inhibitors antithrombin III and
protein C are lowered as a result of complex formation with multiple activated
clotting factors. In addition, their activity can further be curtailed by
proteolytic inactivation. Loss of antithrombin III and protein C activity blocks
the endogenous control mechanism for thrombin generation resulting in a state of
systemic activation of coagulation and inflammatory processes. Levels of tissue
factor pathway inhibitor, a third endogenous coagulation inhibitor, are increased
in sepsis rather than decreased, probably reflecting a depletion of the
endothelial cell bound tissue factor pathway inhibitor pool with loss of its
endothelial protective function. Administration of any of these three inhibitors
in various animal species and sepsis models reduces morbidity and mortality. In
addition to their anticoagulant effects, these inhibitors also have various anti
inflammatory activities that may contribute to their protective effects. Phase II
studies in patients with severe sepsis using coagulation inhibitors have
indicated that this therapeutic approach may be useful. Large-scale phase III
trials will ultimately decide whether adjunctive coagulation inhibitor
replacement will have a place in the treatment of patients with severe sepsis.
PMID- 11007203
TI - Coagulation inhibitor replacement during sepsis: useless?
AB - OBJECTIVE: Because coagulatory activation in sepsis is triggered mainly by tissue
factor release from endothelial cells and blood monocytes during their activation
via proinflammatory cytokines, inhibition of coagulation by exogenous
administration of coagulation inhibitors has been proposed. These strategies
should allow us to prevent and treat excessive coagulatory activation, thereby
potentially preventing sepsis-induced organ dysfunction. Potential therapies
include the natural coagulation inhibitors antithrombin, activated protein C, and
tissue factor pathway inhibitor, as well as direct thrombin inhibition by
recombinant hirudin. DATA SOURCES: A limited review of the published literature
using all sources was undertaken. STUDY SELECTION: Selected clinical and
experimental studies with coagulatory inhibitors were analyzed. CONCLUSIONS: The
biological properties of coagulatory activation during sepsis (coagulation as a
protective mechanism to control the septic focus, e.g., fibrin deposition during
peritonitis) are not completely understood. Therefore, one has to be careful when
administering coagulatory inhibitors, especially because patients with multiple
organ dysfunction syndrome often do not show the widespread fibrin deposition in
nutritive blood vessels that have been seen experimentally. How might these
patients benefit from thrombin inhibition? Coagulatory activation per se seems
unlikely to directly cause deterioration of organ function, although it is
involved in generalized endothelial activation with consecutive mediator release
and increased leukocyte-endothelial cell interaction. Antagonism of inflammatory
mediators and, consecutively, endothelial cell activation might be a better
target in adjunctive sepsis therapy, with improvement in septic microcirculatory
disturbances. Administration of natural pleiotropic coagulation inhibitors that
are documented positive effects on the microcirculation, (such as activated
protein C, antithrombin) seems to be promising.
PMID- 11007204
TI - Phylogenetic and functional relationships between coagulation and the innate
immune response.
AB - Activation of the coagulation system frequently accompanies systemic inflammatory
states and is an almost invariable consequence of septic shock. The simultaneous
activation of the innate immune response and the coagulation system after injury
is a phylogenetically ancient, adaptive response that can be traced back to the
early stages of eukaryotic evolution. Most invertebrate species lack
differentiated phagocytic cells and platelets. They possess a common cellular and
humoral pathway of inflammation and clotting after a breach in their internal
milieu by either trauma or infection. The close linkage between clotting and
inflammation has been preserved throughout vertebrate evolution and is readily
demonstrable in human physiologic responses to a variety of potentially injurious
stimuli. The same proinflammatory stimuli that activate the human clotting
cascade also activate the phagocytic effector cells (neutrophils, monocytes, and
macrophages). The complex and highly integrated linkage between systemic
inflammation and coagulation are reviewed in this article.
PMID- 11007205
TI - Roundtable I: relationships between coagulation and inflammatory processes.
PMID- 11007206
TI - New therapeutic implications of anticoagulation mediator replacement in sepsis
and acute respiratory distress syndrome.
AB - OBJECTIVE: To examine the relationship between the coagulation and immune systems
in sepsis and acute respiratory distress syndrome and to review published
experimental and clinical studies that use anticoagulation mediator replacement
strategies in these conditions. DATA SOURCES: MEDLINE database and bibliographies
of relevant articles. STUDY SELECTION: Articles (both original and review)
relating to coagulation abnormalities and anticoagulation mediator replacement
therapy in sepsis and acute respiratory distress syndrome. DATA EXTRACTION: All
applicable data were extracted. CONCLUSIONS: Coagulation abnormalities are common
in the critically ill. Early studies using anticoagulation mediator replacement
in patients with sepsis have suggested beneficial effects on organ function and
outcome. The results from larger, randomized controlled trials are eagerly
anticipated.
PMID- 11007207
TI - Roundtable II: clinical implications of anticoagulation mediator replacement in
sepsis and acute respiratory distress syndrome.
PMID- 11007208
TI - Concluding discussion of the Margaux Conference on Critical Illness: activation
of the coagulation system in critical illnesses.
PMID- 11007209
TI - Esophagogastric cancer--time to change the paradigm.
PMID- 11007210
TI - Autism and the gastrointestinal tract.
PMID- 11007211
TI - The effect of alcohol on body composition.
PMID- 11007212
TI - Management of recurrent hepatitis C after liver transplantation: a concise
review.
AB - Recurrent hepatitis C infection and subsequent graft failure are increasingly
recognized problems after orthotopic liver transplantation. Although many
prospective therapeutic, controlled trials in primary hepatitis C disease have
been reported, large-scale studies are yet to be performed in patients with
posttransplant recurrent hepatitis C after liver transplantation. In this review,
we summarize the current literature on the therapeutic approaches for recurrent
hepatitis C and discuss the results of published studies on therapy with
ribavirin or interferon (IFN) alone and on combination therapy with IFN plus
ribavirin. Further, we discuss results of prophylactic approaches to the problem
of recurrent hepatitis C after transplant. Finally, we discuss additional aspects
of anti-hepatitis C virus therapy after liver transplantation.
PMID- 11007213
TI - Herpes simplex virus esophagitis in the immunocompetent host: an overview.
AB - OBJECTIVE: The aim of this study was to delineate the characteristics of herpes
simplex virus esophagitis (HSVE) in the immunocompetent host. METHODS: The study
entailed a case report and a review of relevant literature through a MEDLINE
search back to 1966. All cases with documented HSVE in patients without
immunosuppression were selected and their characteristics defined. RESULTS: A
total of 38 cases were identified. The age range was 1-76 yr and the male/female
ratio 3.2/1. Antecedent exposure to HSV disease was described in eight cases
(21.1%). A prodrome of systemic manifestations preceded the onset of esophageal
symptoms in nine subjects (23.6%). Manifestations included acute odynophagia
(76.3%), heartburn (50%), and fever (44.7%). Concurrent oropharyngeal lesions
were uncommon (n = 8, 21.1%). Endoscopically, extensive involvement was common,
showing friable mucosa (84.2%), numerous ulcers (86.8%), and whitish-exudates
(39.5%). The distal esophagus was most commonly affected (63.8%). Microscopic
examination showed characteristic viral cytopathology in 26 (68.4%) cases. Virus
was recovered from esophageal-brushes or biopsies in 23 of 24 (95.8%) patients
and immunocytochemistry was positive in seven of eight (87.5%) cases. Immune
status was consistent with primary HSV infection in eight (21.1%) cases. The
disease was self-limiting, although esophageal perforation and upper GI bleeding
were reported in one case each. CONCLUSIONS: HSVE in the immunocompetent host is
a rare but distinct entity, and is significantly more common in male subjects. It
represents either primary infection or reactivation, and is characterized by
acute onset, systemic manifestations, and extensive erosive-ulcerative
involvement of the mid-distal esophagus. Histopathological examination alone may
miss the diagnosis; adding tissue-viral culture optimizes the diagnostic
sensitivity. It is usually self-limiting; whether antiviral therapy is beneficial
remains unknown.
PMID- 11007214
TI - Results of photodynamic therapy for ablation of dysplasia and early cancer in
Barrett's esophagus and effect of oral steroids on stricture formation.
AB - OBJECTIVE: The primary goal of this study was to investigate whether oral
steroids would reduce the incidence of stricture formation after photodynamic
therapy (PDT) in Barrett's patients. The effect of balloon window length,
pretreatment of nodules, retreatment of skipped areas, and subsequent PDT on the
incidence of strictures was also investigated. The ultimate goal of treatment was
elimination of dysplasia, early cancer, and Barrett's mucosa. METHODS: A total of
60 patients were injected with Photofrin (2 mg/kg). Patients were randomized to
receive PDT (n = 30) or PDT and oral prednisone (n = 30). Two days later, 630 nm
light (KTP/dye laser) was delivered using a 5- or 7-cm windowed balloon at a
light dose of 200 or 175 J/cm. The majority of patients received 200 J/cm using a
7-cm balloon. Nodules were pretreated with a short diffuser at a dose of 50-75
J/cm. Additional light was delivered to skipped areas 2-3 days later. Endoscopies
were conducted every 3-6 months to evaluate the response. Residual or recurrent
Barrett's was treated using neodymium:aluminum-yttrium-garnet (Nd:YAG) laser
(small areas) or was retreated with PDT. RESULTS: The effect of steroids on the
incidence of strictures was analyzed in patients receiving a single treatment
with a light dose of 200 J/cm using a 7- cm balloon. There was no reduction in
the incidence of strictures in patients receiving PDT and steroids (29%) compared
to those receiving PDT alone (16%). Treatment using a 7-cm balloon caused more
strictures (31%) than treatments using a 5-cm balloon (7%). Pretreatment of
nodules or retreatment of skipped areas did not increase strictures. Patients
receiving subsequent PDT had a higher incidence of strictures. Cancer was
eliminated in all patients. High-grade dysplasia was eliminated in 41 of 43
patients (96%). Barrett's mucosa was totally eliminated in 25 of 60 patients
(42%). CONCLUSIONS: Oral prednisone after PDT did not reduce the incidence of
strictures. Subsequent PDT and longer balloon window were associated with higher
incidence of strictures. PDT followed by thermal ablation of small islands
eliminated dysplasia, early cancer, and Barrett's mucosa.
PMID- 11007215
TI - Expandable metal stents in achalasia--is there a role?
AB - OBJECTIVE: Achalasia is treated with pneumatic dilation or myotomy, and botulinum
toxin injections are occasionally used. We review our community's experience with
expandable metal stents in six patients who failed medical treatment or were poor
surgical candidates. METHODS: Eight stents were placed in six patients between
July 1995 and November 1997. Four patients had achalasia and two pseudoachalasia.
Four patients underwent successive botulinum toxin injections. One patient only
agreed to periodic Maloney dilatations or a stent. Pneumatic dilation was
performed in one patient and considered high risk in the rest. All were poor
surgical candidates. Three different stents were used: Gianturco Rosch Z stent,
Wallstent I, and Wallstent II. RESULTS: One-month mortality and morbidity were
33% and 50%, respectively. Two patients were asymptomatic on a liquid diet for >
or =6 months but required repeat endoscopy for recurrent dysphagia because of
food bolus impaction and proximal stent migration in each. CONCLUSIONS:
Expandable metal stents in achalasia or pseudoachalasia do not provide sustained
symptom relief, and their use is associated with unacceptably high morbidity and
mortality. We do not recommend the use of these devices in patients who have
failed medical therapy or who are poor surgical candidates.
PMID- 11007216
TI - Intraesophageal acid perfusion sensitizes the esophagus to mechanical distension:
a Barostat study.
AB - OBJECTIVE: The pathogenesis of noncardiac chest pain is unclear. Increased
gastroesophageal reflux and decreased pain thresholds to intraesophageal balloon
distension have been demonstrated in a proportion of such patients. We aimed to
investigate whether acid exposure sensitizes esophageal mechanoreceptors in
healthy volunteers. METHODS: After an overnight fast, an infinitely compliant
balloon, 4.5 cm in length and mounted on a multilumen transnasal manometry
catheter, was placed 8.5 cm above the lower esophageal sphincter in 12 healthy
male volunteers aged 18-39 yr. After determination of the minimal distending
pressure, the balloon was inflated up to 48 mm Hg by means of a computer
controlled barostat (G & J Electronics, Canada). Graded stepwise distensions were
interspersed with random decreases in pressure to two-thirds of the previous
value. At each pressure level, the subjects were asked to report on sensation and
the presence of pain. Baseline distension was repeated to determine
reproducibility of the pressure/volume relationship and also the perception and
pain thresholds. After the baseline distension sequence, the esophagus was
perfused for 20 min (at 7 ml/min) with either normal saline (control) or 0.1 N
hydrochloric acid at 37 degrees C on a random basis. RESULTS: Basal sensory
thresholds varied widely (first perception 5-36 mm Hg, pain 8 > or = 43 mm Hg).
Two subjects did not experience pain up to the maximum distending pressure (42
and 43 mm Hg, respectively, after correction for the minimal distending
pressure). Esophageal body compliance was similar on repeat distension. Sensory
thresholds were reproducible with different distensions (perception r = 0.99,
pain r = 0.95). Saline resulted in no significant changes in perception or pain
thresholds. Acid perfusion reduced first perception (median before and after
acid, 15 mm Hg and 8 mm Hg, respectively, p = 0.05) and pain threshold (median
before and after acid, 32.5 mm Hg and 26.5 mm Hg, respectively, p = 0.05). When
compared to changes after saline perfusion, acid perfusion reduced the perception
threshold (median change, -3.8 mm Hg vs 0 mm Hg, p = 0.04) and tended to reduce
the pain threshold (median change, -3.75 mm Hg vs +0.75 mm Hg, p = 0.09).
CONCLUSIONS: Intraesophageal balloon distension using a barostat is a
reproducible method of measuring esophageal body compliance and sensory
thresholds. Acute exposure to acid seems to sensitize the esophagus to perception
from intraluminal balloon distension.
PMID- 11007217
TI - Endoscopic and histological comparison of nonulcer dyspepsia with and without
Helicobacter pylori infection evaluated by the modified Sydney system.
AB - OBJECTIVE: Our aim was to identify endoscopic features associated with
Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia.
METHODS: A total of 50 infected patients with nonulcer dyspepsia who underwent
endoscopy with antral and corporal biopsies and 50 patients matched for age and
sex but with nonulcer dyspepsia without H. pylori were reviewed retrospectively
by three endoscopists blinded to the H. pylori status and the patient's history.
The endoscopic findings of gastritis, classified by a modification of the Sydney
system as present or absent, were evaluated, and the histological severity was
graded by the updated Sydney system. RESULTS: For endoscopic features, the odds
ratio was 53.1 (95% confidence interval, 6.8-414.9) for edema, 18.8 (5.8-60.5)
for erythema with reddish streaks excluded, 0.0275 (0.0002-0.477) for reddish
streaks, 17.4 (0.97-313.7) for friability, 14.2 (5.1-40.0) for exudate, 17.2 (2.2
137.6) for flat erosions, 2.54 (0.81-7.94) for raised erosions, 40.1 (2.3-694.5)
for rugal hypertrophy, 19.1 (2.4-151.6) for rugal atrophy, 96.2 (23.4-395.9) for
a vascular pattern, 0.125 (0.010-1.06) for bleeding spots, and 21.0 (2.6-166.5)
for nodularity. The histological severity of inflammation, neutrophil activity,
and atrophy in the antrum and corpus and of metaplasia in the antrum was greater
in the infected patients than in the noninfected patients. CONCLUSIONS:
Endoscopic features associated with H. pylori were a vascular pattern, edema,
rugal hypertrophy, nodularity, rugal atrophy, erythema with reddish streaks
excluded, flat erosions, and exudate. These endoscopic features were associated
with the histological findings of inflammation, neutrophil activity, atrophy, and
metaplasia.
PMID- 11007218
TI - Accuracy of an enzyme immunoassay for the detection of Helicobacter pylori in
stool specimens in the diagnosis of infection and posttreatment check-up.
AB - OBJECTIVE: The aim of this study was to assess the reliability of a newly
developed enzyme immunoassay for Helicobacter pylori-specific antigen detection
in stools (HpSA) compared to other standardized diagnostic techniques such as
histology (H), rapid urease test (RUT) and 13C-urea breath test (UBT) to diagnose
H. pylori infection and to evaluate its usefulness in determining H. pylori
status after treatment. METHODS: One hundred eighty-eight patients referred to
our department for upper gastrointestinal endoscopy were included. H. pylori
infection was confirmed in all patients by HpSA test in stools, RUT, UBT, and H.
Patients were defined as positive for H. pylori if RUT and UBT or H were
positive. A total of 142 symptomatic patients received eradication treatment and
were reassessed 6 wk after therapy; for 70 of these patients, stool samples were
also collected at 24 h and 6 months after finishing eradication treatment. In the
posttreatment follow-up, UBT was used as gold standard. RESULTS: The sensitivity
of HpSA test for the diagnosis of H. pylori infection using a cut-off value of
0.130 was 89.5% and its specificity 77.8%. This specificity was lower than that
obtained with UBT, H, and RUT. In the early follow-up the sensitivity of HpSA
test was null. At 6 weeks and at 6 months post-treatment its sensitivity was
70.4% and 50% and its specificity was 81.6% and 79.3%, respectively. CONCLUSIONS:
The HpSA stool test, using a cut-off value of 0.130, may be useful for the
primary diagnosis of H. pylori infection, with sensitivity similar to that
obtained with other standard tests, but with less specificity. HpSA test is not
useful for early monitoring of treatment efficacy. At 6 wk and at 6 months
posttreatment, HpSA test lacks accuracy as compared to UBT for evaluating the
outcome of the eradication treatment.
PMID- 11007219
TI - CagA-positive strains of Helicobacter pylori may protect against Barrett's
esophagus.
AB - OBJECTIVE: Helicobacter pylori (H. pylori) colonization is associated with
chronic gastritis, peptic ulcer disease, and adenocarcinoma of the distal
stomach. However, the role of H. pylori strain variation in complicated
gastroesophageal reflux disease, especially Barrett's esophagus, is unknown.
Therefore, the aim of this study was to evaluate the prevalence of colonization
by cagA+ and cagA- H. pylori strains in the spectrum of gastroesophageal reflux
disease, including Barrett's esophagus. METHODS: A total of 251 patients
undergoing endoscopy were categorized into four groups: controls, patients with
gastroesophageal reflux disease alone, and patients with short- and long-segment
Barrett's esophagus. All patients underwent upper endoscopies with biopsies and
serum collections. H. pylori and degree of mucosal inflammation in gastric
biopsies were assessed and serological assessment made for H. pylori and cagA
status. RESULTS: The overall prevalence of H. pylori colonization in the study
population was 35% (95% confidence interval = 29.5-41.4%) which did not differ
significantly among the groups. However, colonization by cagA+ H. pylori strains
was significantly more prevalent among controls (11/25; 44%) and patients with
gastroesophageal reflux disease (13/36; 36%) than in patients with short-segment
(2/10; 20%) or long-segment Barrett's esophagus (0/18; 0%). Patients with
Barrett's esophagus were less likely to be colonized by cagA+ H. pylori strains
than reflux patients without Barrett's esophagus (odds ratio = 0.27, 95%
confidence interval = 0.11-0.67, p = 0.004). CONCLUSIONS: Colonization by cagA+
H. pylori strains may be protective against the formation of short- and long
segment Barrett's esophagus and its malignant complications.
PMID- 11007220
TI - Treatment of uninvestigated dyspepsia with cisapride for patients with negative
Helicobacter pylori serologies.
AB - OBJECTIVE: The aim of this study was to compare symptoms for patients with
uninvestigated dyspepsia and a negative Helicobacter pylori serology who were
treated with cisapride or placebo. METHODS: Helicobacter pylori-seronegative
patients with chronic dyspepsia were randomized to receive cisapride 10 mg t.i.d.
or placebo t.i.d. for 30 days. Symptom scores were performed 1 month and 3 months
after randomization. Outcomes measured were dyspepsia symptom scores and a
treatment "success" variable defined as absence of symptoms or decrease in the
most severe individual symptom by two grades. RESULTS: A total of 60 patients
were randomized; 56 completed the 1-month follow-up and 40 completed the 3-month
follow-up interview. The mean score for all patients at the time of entry was
11.0 and declined to 8.3 and 8.2 at 1 and 3 months, respectively, after
randomization. At 1 month and 3 months after randomization, there was no
significant difference in the number of patients meeting the "success" variable
for patients receiving cisapride as compared to placebo. The mean decline in
symptom severity scores was not significantly different for patients receiving
placebo or cisapride at 1 month (mean, -2.8 vs -3.1; difference = 0.3, p = 0.74)
or 3 months (-3.1 vs -2.6, difference = -0.5, p = 0.58) after randomization.
CONCLUSIONS: No significant difference in the severity of dyspeptic symptoms was
found for patients receiving cisapride as compared to placebo in the setting of
uninvestigated dyspepsia and a negative Helicobacter pylori serology.
PMID- 11007221
TI - Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin.
AB - OBJECTIVE: Aspirin products are known to cause irritation and injury to the
gastric mucosa. We examined the risk of hospitalization for upper
gastrointestinal bleeding with use of low-dose aspirin. METHODS: This was a
cohort study based on record linkage between a population-based prescription
database and a hospital discharge registry in North Jutland County, Denmark, from
January 1, 1991, to December 31, 1995. Incidence rates of upper gastrointestinal
bleeding in 27,694 users of low-dose aspirin were compared with the incidence
rates in the general population in the county. RESULTS: A total of 207 exclusive
users of low-dose aspirin experienced a first episode of upper gastrointestinal
bleeding with admission to the hospital during the study period. The standardized
incidence rate ratio was 2.6 (95% confidence interval, 2.2-2.9), 2.3 in women and
2.8 in men. The standardized incidence rate ratio for combined use of low-dose
aspirin and other nonsteroidal anti-inflammatory drugs was 5.6 (95% confidence
interval, 4.4-7.0). The risk was similar among users of noncoated low-dose
aspirin (standardized incidence rate ratio, 2.6; 95% confidence interval, 1.8
3.5) and coated low-dose aspirin (standardized incidence rate ratio, 2.6; 95%
confidence interval, 2.2-3.0). CONCLUSIONS: Use of low-dose aspirin was
associated with an increased risk of upper gastrointestinal bleeding, with still
higher risks when combined with other nonsteroidal anti-inflammatory drugs.
Enteric coating did not seem to reduce the risk. The findings from this
observational study raise the possibility that prophylactic use of low-dose
aspirin may convey an increased risk of gastrointestinal bleeding, which may
offset some of its benefits.
PMID- 11007222
TI - Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage--a
long-term randomized, controlled study.
AB - OBJECTIVE: Eradication of Helicobacter pylori (H. pylori) in patients with
uncomplicated duodenal ulcers prevents long-term recurrence of ulcers. We aimed
to study whether treatment of H. pylori prevents the long-term recurrence of
duodenal ulcer hemorrhage. METHODS: Patients with duodenal ulcer bleeding and
confirmed H. pylori infection were recruited. A total of 120 patients were
randomly assigned to triple therapy (DeNoltab 120 mg, amoxycillin 500 mg, and
metronidazole 300 mg four times daily) or DeNoltab 120 mg four times daily alone.
No maintenance therapy was given during the follow-up period. The endpoints were
the cumulative rates of symptomatic and bleeding duodenal ulcer recurrences.
RESULTS: Of the patients receiving the triple regimen, 85.1% had H. pylori
eradicated as compared to 2.0% of patients receiving DeNoltab (p < 0.05). More
patients in the DeNoltab group than those in the Triple group had recurrence of
ulcer bleeding, but this did not reach statistical significance (12/60 vs 6/60, p
= 0.20). Logistic regression analysis on clinical, personal, and endoscopic
characteristics identified persistent H. pylori infection as the only independent
predictor of recurrence of duodenal ulcer bleeding. CONCLUSIONS: Treatment of H.
pylori alone with the present bismuth-based triple therapy in patients with
duodenal ulcer hemorrhage did not result in significant reduction in further
bleeding episodes, although a trend was seen for the group that was given triple
therapy. On the other hand, posttreatment H. pylori status was found to be an
independent predictor of bleeding recurrence.
PMID- 11007223
TI - The stimulation of antral motility by erythromycin is attenuated by
hyperglycemia.
AB - OBJECTIVE: Diabetic gastroparesis is usually treated with prokinetic drugs, of
which the most potent, when given intravenously during euglycemia, is
erythromycin. Recent studies have demonstrated that the gastrokinetic effects of
erythromycin are attenuated by hyperglycemia. The aim of this study was to
determine whether the effects of erythromycin on antropyloroduodenal motility,
including the organization of antral pressure waves, are modified by
hyperglycemia. METHODS: A total of eight healthy male volunteers (median age 24
yr) were studied on 2 days each in randomized order. A manometric assembly,
incorporating six antral, two pyloric, and seven duodenal sideholes and a pyloric
sleeve sensor, was positioned with the sleeve spanning the pylorus. The blood
glucose concentration was stabilized at about 5 mmol/L (euglycemia) or 15 mmol/L
(hyperglycemia). After 30 min (T = 0), an intraduodenal lipid infusion (1.5
kcal/min) was commenced and continued until the end of the study. At T = 20
minutes, erythromycin (200 mg) as the lactobionate was infused intravenously over
20 min, followed by 100 mg over the next 40 min. RESULTS: Intravenous
erythromycin increased the amplitude of antral waves during intraduodenal lipid
infusion at both blood glucose concentrations (p < 0.01 for euglycemia and p <
0.05 for hyperglycemia). After erythromycin (T = 20 to T = 80), the frequency (p
< 0.05) and amplitude (p < 0.01) of antral waves were less during hyperglycemia
than euglycemia. Both propagated (p < 0.0005) and nonpropagated (p < 0.01) antral
waves were decreased by hyperglycemia, but the suppression of propagated waves
was greater (p < 0.05). Erythromycin reduced the frequency (p = 0.09) but
increased the amplitude (p < 0.05) of phasic pyloric pressures, and decreased
basal pyloric pressure (p < 0.0005). The frequency (p = 0.06) and amplitude (p <
0.05) of phasic pyloric waves during erythromycin infusion were slightly less
during hyperglycemia than euglycemia, whereas there was no effect of the blood
glucose concentration on basal pyloric pressure. Erythromycin increased the
amplitude (p < 0.001) but not the frequency of duodenal waves; the frequency and
amplitude of duodenal waves did not differ between the two blood glucose
concentrations. CONCLUSIONS: Hyperglycemia attenuates the stimulation of antral
pressures and propagated antral sequences by erythromycin, but not the effects of
erythromycin on pyloric or duodenal motility.
PMID- 11007224
TI - Sedation for colonoscopy using a single bolus is safe, effective, and efficient:
a prospective, randomized, double-blind trial.
AB - OBJECTIVE: Practice guidelines call for the careful titration of sedatives and
analgesics during endoscopy, with time taken between incremental doses to assess
effect. This approach is time-consuming and has never been validated in a
prospective trial. The aim of this study was to compare the safety and efficacy
of titration, as outlined in practice guidelines, with a single, rapid bolus of
sedatives before colonoscopy. METHODS: Consecutive colonoscopy outpatients were
randomized to a single, rapid bolus of meperidine and midazolam or to a titration
of doses every 3 min until predefined levels of somnolence were achieved. The
colonoscopist was not present during sedation and remained blinded as to which
technique was used. Supplemental O2 was given for SaO2 <90% on three or more
occasions. Total physician time was calculated from the first injection of
sedatives to the removal of the colonoscope. Patient assessments of pain and
tolerance were obtained at the time of discharge using visual analog scales of
100 mm (0 = excellent and 100 = unbearable). RESULTS: A total of 101 patients
were randomized (49 bolus, 52 titration). Demographic features were similar for
both groups. Titration required more physician time than did bolus (32.2 min vs
20.1 min, p < 0.001) and was associated with an increased need for supplemental
O2 (44% vs 14%, p = 0.002). Mean tolerance scores were similar (titration 16.3 vs
bolus 15.3, p = 0.72). CONCLUSIONS: Rapid bolus sedation for colonoscopy saves
significant endoscopist time, is associated with less O2 desaturation, and
provides equivalent levels of patient comfort. A revision of the guidelines for
sedation and analgesia during endoscopy should be considered.
PMID- 11007225
TI - Impact of endoscopic ultrasound on the management and outcome of pancreatic
carcinoma.
AB - OBJECTIVE: Although endoscopic ultrasound and endoscopic ultrasound-guided fine
needle aspiration have been shown to aid in the diagnosis and staging of
pancreatic carcinoma, whether the general use of these new techniques impacts the
overall management and survival of pancreatic cancer, is less clear. METHODS:
Clinical data on all patients diagnosed with pancreatic carcinoma were assessed
for two equal time periods during which computerized tomography-guided fine
needle aspiration and biopsy was used (1/93-5/95) and then during which
endoscopic ultrasound-guided fine needle aspiration was used (8/95-12/97) for the
primary diagnosis of these patients. RESULTS: Comparative data for the
computerized tomography era versus the endosonography era showed that 1)
pancreatic carcinomas diagnosed: 52 versus 84 patients (stage I-III at diagnosis:
33% vs 54%; p < 0.05); 2) diagnosis by aspiration or biopsy of a pancreatic mass,
nodes, liver metastasis, or by operation: 46%, 0%, 19%, 29% versus 52%, 8% (p =
0.02 nodes plus pancreatic masses), 20%, 7% (p = 0.002); 3) pancreatic
resections: 13% versus 14%; 4) median survival without liver metastases: 102
versus 205 days (p < 0.02, log-rank test). Endoscopic ultrasound detected
carcinomas that were either not seen or only possibly seen by computed tomography
in 34%. CONCLUSIONS: More patients (62%) were diagnosed with pancreatic carcinoma
when using endoscopic ultrasound and 75% fewer required operations for diagnosis.
The 3-month improvement in median survival is probably multifactorial but most
likely represents lead bias because of the greater sensitivity of endoscopic
ultrasound for pancreatic carcinoma. Using endoscopic ultrasound with endoscopic
ultrasound-guided fine needle aspiration in patients with pancreatic carcinoma
significantly affects their management and outcomes.
PMID- 11007226
TI - Endosonography-guided, fine-needle aspiration cytology extending the indication
for organ-preserving pancreatic surgery.
AB - OBJECTIVE: Organ preserving pancreatic resections are considered whenever
malignant disease is ruled out. In tumors of low malignant potential such as
cystadenomas and neuroendocrine tumors, the diagnosis is rarely established
preoperatively. We studied the feasibility of cytodiagnosis using endosonography
guided fine-needle aspiration in determining the operative approach. METHODS: A
total of 78 patients (16 female, 62 male; mean age 61.4 yr, range 31-82 yr) with
focal pancreatic lesions underwent EUS-FNA. Final diagnosis was confirmed by
histology, cytology, or clinical follow up (>9 months). Patients with tumors of
low malignant potential were managed by customized pancreatic resections.
RESULTS: Final diagnosis was malignant tumors in 36 patients, tumors of low
malignant potential in nine (six, neuroendocrine, two, borderline mucinous
cystadenomas, one, borderline adenocarcinoma), and benign in 31 (two inadequate
smears). No complications occurred. With six false-negative and no false-positive
results, the accuracy, sensitivity, specificity, and positive and negative
predictive values were 92%, 84%, 100%, 100%, and 86%, respectively. Five patients
with low malignant tumors underwent duodenum-preserving pancreatic head
resection, three mid segment resection, and one pylorus-preserving
pancreatoduodenectomy. CONCLUSIONS: EUS-FNA is useful in the preoperative
cytodiagnosis of pancreatic tumors of low malignant potential. It extends the
indication for organ-preserving pancreatic resections and avoids the unnecessary
sacrifice of adjacent organs.
PMID- 11007227
TI - Modern imaging methods versus clinical assessment in the evaluation of hospital
in-patients with suspected pancreatic disease.
AB - OBJECTIVE: Various modern imaging procedures such as endoscopic retrograde
cholangiopancreatography (ERCP), computed tomography (CT), and endoscopic
ultrasonography (EUS) have been shown to be highly accurate in the diagnosis of
specific disorders of the pancreas. However, prior information often causes bias
in the interpretation of these results. Little information is available
concerning the value of these examinations in the primary and differential
diagnosis of suspected pancreatic disease-particularly in comparison with
clinical evaluation, including laboratory tests and transabdominal ultrasound
(TUS). METHODS: Clinical and imaging information (EUS, ERCP, and CT) was
collected for 184 inpatients who were referred over a 5-yr period for evaluation
of suspected pancreatic disease. On the basis of patient history, laboratory
tests, and the results of routine TUS, one gastroenterologist, who was unaware of
any of the other procedures or the final diagnosis, made a presumptive clinical
diagnosis. CT and ERCP images and EUS videotapes were then analyzed by three
different and independent examiners, who had the same clinical information except
for the TUS results, but were completely blinded to the results of the other
examinations and the patients' diagnoses. The final diagnoses were obtained by
surgery, histology, and cytology, plus a follow-up of at least 1 yr (mean 35
months) in all noncancer cases. RESULTS: The final diagnoses were: normal
pancreas (n = 36), chronic pancreatitis without a focal inflammatory mass (n =
53) or with a focal inflammatory mass (n = 18), and pancreatic malignancy (n =
77). Clinical evaluation, including ultrasonography, achieved a sensitivity for
pancreatic disease of 94% but a specificity of only 35%. The figures for the
sensitivity and specificity of the three imaging procedures were 93% and 94%,
respectively, for EUS; 89% and 92% for ERCP; and 91% and 78% for CT (p < 0.05 for
the specificity of clinical assessment vs all three imaging tests, p > 0.05 for
comparison of the three imaging procedures). In the differential diagnosis
between cancer and chronic pancreatitis as well as between malignant and
inflammatory tumors, there was no difference among clinical assessment and the
three imaging tests. CONCLUSIONS: In a group of patients with a high suspicion of
pancreatic disease, little additional sensitivity in the diagnosis of pancreatic
disease is provided by sophisticated imaging procedures such as EUS, ERCP, and
CT, in comparison with clinical assessment including laboratory values and TUS.
However, the specificity can be substantially improved. To confirm the diagnosis,
one of the three examinations is needed, depending on the suspected disease and
local expertise. The imaging procedures should be performed in a stepwise fashion
for specific purposes, such as exclusion of pancreatic disease and the planning
of treatment in chronic pancreatitis and pancreatic cancer.
PMID- 11007228
TI - Endoscopic ultrasound is highly accurate and directs management in patients with
neuroendocrine tumors of the pancreas.
AB - Preoperative localization of pancreatic neuroendocrine tumors with traditional
imaging fails in 40-60% of patients. Endoscopic ultrasound (EUS) is highly
sensitive in the detection of these tumors. Previous reports included relatively
few patients or required the collaboration of multiple centers. We report the
results of EUS evaluation of 82 patients with pancreatic neuroendocrine tumors.
METHODS: We prospectively used EUS early in the diagnostic evaluation of patients
with biochemical or clinical evidence of neuroendocrine tumors. Patients had
surgical confirmation of tumor localization or clinical follow-up of >1 yr.
RESULTS: Eighty-two patients underwent 91 examinations (cases). Thirty patients
had multiple endocrine neoplasia syndrome type 1. One hundred pancreatic tumors
were visualized by EUS in 54 different patients. The remaining 28 patients had no
pancreatic tumor or an extrapancreatic tumor. Surgical/pathological confirmation
was obtained in 75 patients. The mean tumor diameter was 1.51 cm and 71% of the
tumors were < or =2.0 cm in diameter. Of the 54 explorations with surgical
confirmation of a pancreatic tumor, EUS correctly localized the tumor in 50
patients (93%). Twenty-nine insulinomas, 18 gastrinomas, as well as one
glucagonoma, one carcinoid tumor, and one somatostatinoma were localized. The
most common site for tumor localization was the pancreatic head (46 patients).
Most tumors were hypoechoic, homogenous, and had distinct margins. EUS of the
pancreas was correctly negative in 20 of 21 patients (specificity, 95%). EUS was
more accurate than angiography with or without stimulation testing (secretin for
gastrinoma, calcium for insulinoma), transcutaneous ultrasound, and CT in those
patients undergoing further imaging procedures. EUS was not reliable in
localizing extrapancreatic tumors. CONCLUSIONS: In this series, the largest
single center experience reported to date, EUS had an overall sensitivity and
accuracy of 93% for pancreatic neuroendocrine tumors. Our results support the use
of EUS as a primary diagnostic modality in the evaluation and management of
patients with neuroendocrine tumors of the pancreas.
PMID- 11007229
TI - Mediastinal lymphadenopathy in patients with or without previous malignancy: EUS
FNA-based differential cytodiagnosis in 153 patients.
AB - OBJECTIVE: Mediastinal lymphadenopathy (ML) is a cause for concern, especially in
patients with previous malignancy. The investigation of choice is thoracic CT
with a variable sensitivity and specificity requiring tissue diagnosis. We used
endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for cytodiagnosis
of ML in patients with and without previous malignancy. The cause, distribution
of lesions, and incidence of second cancers were investigated. METHODS: Linear
echoendoscopes and 22-gauge needles for cytology were used for EUS-FNA. A
cytological diagnosis of malignancy was accepted, and histology or consistent
follow-up of at least 9 months confirmed benign results. RESULTS: One hundred
fifty-three patients underwent EUS-FNA between November 1997 and November 1999
(mean age, 60 yr; range, 13-82 yr; 105 men). Cytology was adequate in 150
patients. Final diagnosis was malignancy in 84 and benign in 66 patients
(sensitivity, specificity, and diagnostic accuracy: 92%, 100%, 95%,
respectively). In 101 patients without previous cancer cytology identified 48
malignant (lung, 41; extrathoracic, 7) and 51 benign lesions (inflammation, 35;
various, 9; sarcoidosis, 7) (sensitivity, specificity, accuracy: 88%, 100%, 94%).
Fifty-two patients had prior malignancy, mostly in extrathoracic sites. Cytology
revealed recurrences in 21 patients, second cancer in 9 and benign lesions in 21
patients (inflammatory, 11; sarcoidosis, 8; tuberculosis, 1; abscess, 1)
(sensitivity, specificity, accuracy: 97%, 100%, 98%). CONCLUSIONS: In patients
without previous cancer malignant ML originates from the lung >80%. In those with
previous malignancy recurrence of extrathoracic sites is the major cause. Benign
lesions and treatable second cancers occur in a significant frequency,
emphasizing the need for tissue diagnosis. EUS-FNA is a safe and minimally
invasive alternative for cytodiagnosis in the mediastinum.
PMID- 11007230
TI - Enterocolitis in children with developmental disorders.
AB - OBJECTIVE: Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia
(LNH) and mucosal inflammation, has been described in children with developmental
disorders. This study describes some of the endoscopic and pathological
characteristics in a group of children with developmental disorders (affected
children) that are associated with behavioral regression and bowel symptoms, and
compares them with pediatric controls. METHODS: Ileocolonoscopy and biopsy were
performed on 60 affected children (median age 6 yr, range 3-16; 53 male).
Developmental diagnoses were autism (50 patients), Asperger's syndrome (five),
disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD)
(one), schizophrenia (one), and dyslexia (one). Severity of ileal LNH was graded
(0-3) in both affected children and 37 developmentally normal controls (median
age 11 yr, range 2-13 yr) who were investigated for possible inflammatory bowel
disease (IBD). Tissue sections were reviewed by three pathologists and scored on
a standard proforma. Data were compared with ileocolonic biopsies from 22
histologically normal children (controls) and 20 children with ulcerative colitis
(UC), scored in an identical manner. Gut pathogens were sought routinely.
RESULTS: Ileal LNH was present in 54 of 58 (93%) affected children and in five of
35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%)
affected children and in two of 37 (5.4%) controls (p < 0.01). Histologically,
reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies
from affected children and in four of 14 (29%) with UC, but not in non-IBD
controls (p < 0.01). Active ileitis was present in four of 51 (8%) affected
children but not in controls. Chronic colitis was identified in 53 of 60 (88%)
affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%)
with UC. Scores of frequency and severity of inflammation were significantly
greater in both affected children and those with UC, compared with controls (p <
0.001). CONCLUSIONS: A new variant of inflammatory bowel disease is present in
this group of children with developmental disorders.
PMID- 11007231
TI - Do male sex hormones protect from irritable bowel syndrome?
AB - OBJECTIVE: Irritable bowel syndrome (IBS) is more common in women and it is
frequently assumed that being female may predispose to the development of this
disorder. Alternatively, being male could offer some degree of protection and if
so, this might be mediated by testosterone. The aim of this study was to assess
whether male patients with IBS have lower levels of testosterone and related
gonadotrophins than their unaffected counterparts and if this relates to rectal
sensitivity. METHODS: Fifty secondary care, male outpatients with IBS (aged 19-71
yr) were compared with 25 controls (aged 22-67 yr). Each subject had serum
testosterone, free testosterone, sex hormone-binding globulin, follicle
stimulating hormone, and luteinizing hormone (LH) measured, together with rectal
sensitivity to balloon distension. Anxiety and depression were also assessed.
RESULTS: The only difference in the hormone levels between patients and controls
that reached statistical significance was the lower value for LH in the IBS
patients (p = 0.014). Although patients were more anxious and depressed than the
controls (p < 0.001), this could not solely account for the reduced level of LH,
as adjusting for these (analysis of variance) still tended to show that LH values
were lower in men with rather than without IBS [F(1,70) = 2.74; p = 0.10]. Men
with IBS were more sensitive to balloon distension of the rectum, with the
distension volumes required for "urgency" (p < 0.001) and "discomfort" (p =
0.001) significantly lower than controls. Paradoxically, the patient's sensory
thresholds negatively correlated with levels of testosterone (p < 0.05) and free
testosterone (p < 0.002), and positively with levels of sex hormone-binding
globulin (p < 0.05). Finally, there was a tendency for IBS symptomatology to be
inversely related to testosterone levels (p = 0.15). CONCLUSIONS: These results
support the need for further exploration of the role of male sex hormones in the
pathophysiology of IBS.
PMID- 11007232
TI - High frequencies of telomeric associations, chromosome aberrations, and sister
chromatid exchanges in ulcerative colitis.
AB - OBJECTIVE: Chromosome instability provides a predisposing background to
malignancy, contributing to the crucial genetic changes in multistep
carcinogenesis. The aim of this work was to analyze chromosome instability in
patients with ulcerative colitis (UC) to achieve a better understanding of the
increased risk for colorectal cancer. METHODS: Peripheral blood lymphocyte
cultures from 20 untreated UC patients and 24 controls were used to study
chromosome instability by assessing telomeric associations (TAS), chromosome
aberrations (CA), and sister chromatid exchanges (SCE). RESULTS: Mean frequencies
of TAS and CA were significantly increased in UC patients compared to controls (p
< 0.001). Chromosomes 10, 11, 21, 16, and 19 were the most frequently involved in
TAS. A total of 104 CA clustered in 66 breakpoints could be exactly localized.
Seven nonrandom bands significantly affected in UC patients were found (p <
0.004), showing a significant correlation with the location of cancer breakpoints
(p < 0.003), particularly with colorectal carcinoma rearrangements. SCE analysis
showed higher levels in patients compared to controls (p < 0.006), but no
differences were observed in cell cycle kinetics. CONCLUSIONS: Our results
demonstrate the presence of an unstable genome in UC patients that could be
related to the cancer development observed in this disease.
PMID- 11007233
TI - Risk of lymphoma in inflammatory bowel disease.
AB - OBJECTIVE: Inflammatory bowel disease with a subsequent diagnosis of non
Hodgkin's lymphoma has been reported. There is concern that the risk of
developing lymphoma will rise with increasing use of immune modifier therapy. We
determined the risk of non-Hodgkin's lymphoma in an U.S. population-based
inception cohort, and evaluated the association between inflammatory bowel
disease and lymphoma in our referral practice. METHODS: The records of all
incidence cases of inflammatory bowel disease in Olmsted County, Minnesota,
between 1950 and 1993 were reviewed for the diagnosis of lymphoma. Standardized
incidence ratios (observed/expected) were used to estimate relative risk. In
addition, the clinical features and outcomes of all patients with inflammatory
bowel disease and lymphoma seen at Mayo Clinic between 1976 and 1997 were
reviewed. RESULTS: Among 454 county residents diagnosed with inflammatory bowel
disease, a single non-Hodgkin's lymphoma occurred in a patient with Crohn's
disease. No cases were seen with ulcerative colitis. The estimated relative risk
of lymphoma was 2.4 in Crohn's disease (95% confidence interval, 0.1-13), 0 in
ulcerative colitis (0-6), and 1.0 in inflammatory bowel disease overall (0.03-6).
Between 1976 and June 1997, 61 patients with inflammatory bowel disease and
lymphoma (approximately 0.41%) were seen in the referral practice. In four
patients with Crohn's disease (13%), potential neoplastic risk factors were
identified-therapeutic radiation in 1, and use of purine analogs in 3 (median
length of use, 11 months). CONCLUSIONS: Our population-based cohort study
demonstrated that the absolute risk of non-Hodgkin's lymphoma remains quite small
(0.01% per person-year). This risk may not exceed that in the general population.
In our referral practice, immune modifier therapy could be potentially implicated
in only 5% of cases of lymphoma occurring in the setting of inflammatory bowel
disease.
PMID- 11007234
TI - Allelic variants of the thiopurine S-methyltransferase deficiency in patients
with ulcerative colitis and in healthy controls.
AB - OBJECTIVE: Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that
catalyzes the inactivation of mercaptopurine, azathioprine, and thioguanine. The
genetic polymorphisms in the TPMT gene that regulate TPMT activity are inherited
as an autosomal recessive trait and patients with genetically determined low
levels of TPMT activity develop severe myelosuppression when treated with
standard doses of the above-mentioned drugs. We have analyzed the frequencies of
the allelic variants of the TPMT gene in a white European population of healthy
blood donors from Spain and The Netherlands, and in a group of patients suffering
from ulcerative colitis (UC) with a similar genetic background. METHODS: Two
hundred and thirteen unrelated healthy individuals (HC) and 146 UC patients were
typed for the polymorphic sites at positions 460 (G-->A) and 719 (A-->G) of the
TPMT gene using specific polymerase chain reaction-restriction fragment-length
polymorphism (PCR-RFLP) methods. RESULTS: There were no significant differences
between the allele frequencies observed in the group of UC patients and those of
the control group (10% of cases were heterozygous carriers of a TPMT mutant
allele). The most frequent mutant allele in both UC and HC groups was TPMT3A
(A460-->G719) (60% of carriers). TPMT3B (A460-->A719) and TPMT3C (G460-->G719)
alleles were more often found in our study than in previously reported studies,
reflecting the different genetic backgrounds of the European populations
analyzed. CONCLUSIONS: Genotyping methods provide a simple and reliable screening
to identify patients with a high risk of developing severe bone marrow toxicity
if treated with thiopurine drugs. In UC patients, TPMT genotype should be
determined before the initiation of azathioprine therapy.
PMID- 11007236
TI - Body composition changes induced by chronic ethanol abuse: evaluation by dual
energy X-ray absorptiometry.
AB - OBJECTIVE: Nutritional disorders in alcoholics remain one of the most relevant
medical problems in Western societies. As ethanol can supply >50% of the dietary
energy in alcoholics, body composition alterations may easily occur. The aim of
the present study was to evaluate the influence of chronic alcohol consumption on
body composition in alcoholics compared to healthy social drinkers. METHODS: A
total of 34 alcoholics defined according to DSM III R criteria, aged 41.6 +/- 9.3
yr and with a body mass index (BMI) 23.8 +/- 3.2 kg/m2, were consecutively
enrolled in the study. In addition, 43 healthy male social drinkers were used as
controls. Body composition was assessed using dual energy x-ray absorptiometry
(DXA), and dietary habits were determined by a 3-day food diary. RESULTS: Mean
daily alcohol intake was 194 +/- 62.4 g/day in alcoholics and 35.7 +/- 5.2 in
healthy subjects (p < 0.0001). Body weight did not differ between alcoholics and
controls (70.1 +/- 9.9 vs 71.8 +/- 6.4 kg). Alcoholics had a lower percent body
fat (PBF) than control subjects (18.7 +/- 3.7 vs 23.9 +/- 3.9%; p < 0.01), as
well as a lower fat mass content (13.4 +/- 3.8 vs 17.0 +/- 3.7 kg; p < 0.01). BMI
was highly correlated with PBF in the patient population studied (R = 0.79; p <
0.0001). Significantly higher waist-to-hip ratios were found in alcoholics than
in healthy subjects (p < 0.01). No correlation was found between dose of ethanol
or duration of alcohol abuse and any of the variables examined. CONCLUSIONS:
Alcoholics showed a reduced fat mass and a good preservation of lean body mass
with respect to control subjects, and duration of alcohol use and alcohol dose
did not seem to influence body composition. These data suggest that, unlike
control subjects, alcoholics cannot store the calories provided by ethanol as fat
deposits.
PMID- 11007235
TI - Tissue transglutaminase antibodies in celiac disease: assessment of a commercial
kit.
AB - OBJECTIVE: Tissue transglutaminase was identified as the autoantigen eliciting
endomysial antibody. A homemade enzyme-linked immunosorbent assay (ELISA)-based
test was recently developed to determine quantitative titers of IgA antitissue
transglutaminase antibody. Our objective in this study was to assess the
suitability of a newly developed commercial kit for quantitative determination of
antibody in patients with untreated celiac disease. MATERIALS: We tested serum
samples from 79 untreated celiac patients, 42 healthy blood donors, and 18
patients with nonceliac intestinal disorders evaluated in two different centers.
Samples were tested for antitissue transglutaminase, and antiendomysial and
antigliadin antibodies in the center where diagnosis was performed. To assess
interlaboratory variability of methods, 24 samples randomly selected were blindly
tested in both centers. Antitissue transglutaminase antibodies were determined
using a commercial kit (INOVA Diagnostics, Inc., San Diego, CA). RESULTS:
Untreated celiac patients had significantly higher titers of antitissue
transglutaminase than healthy and disease controls (p < 0.00001). According to
the cut-off provided by the manufacturers (20 AU/mL), overall sensitivity was 92%
(85% for one center and 100% for the other) and specificity was 98% (100% and
95%, respectively). Antiendomysial antibody was 86% sensitive and 100% specific.
Discordance between antitissue transglutaminase and antiendomysial antibodies was
detected in 13% of patients. Although two antitissue transglutaminase-negative
cases had a positive antiendomysial antibody, the inverse situation was found in
eight cases. A blind determination of antitissue transglutaminase on the same
samples evidenced a good agreement (kappa statistic: 0.66) between both centers
when assessment was qualitative (based on the decision of positive or negative).
Although correlation of titers for both determinations was highly significant (r:
0.902, p < 0.00001), a very wide interlaboratory variability (median: 50%) was
detected when absolute values were considered. CONCLUSIONS: The quantitative
determination of antitissue transglutaminase using a commercial kit was highly
sensitive and specific for detection of celiac disease. We observed an incomplete
overlapping with antiendomysial antibody. The very high variability of values
between laboratories still remains to be solved so as to propose the commercial
ELISA assay for the screening of celiac disease.
PMID- 11007237
TI - Need for validation of clinical decision aids: use of the AST/ALT ratio in
predicting cirrhosis in chronic hepatitis C.
AB - OBJECTIVE: A value of > or = 1 for the ratio of aspartate amino-transferase to
alanine aminotransferase (the AST/ALT ratio or AAR) has been shown to have a
positive predictive value of 100% for the diagnosis of cirrhosis in patients with
chronic hepatitis C. If validated on separate cohorts, an AAR > or = 1 might
obviate the need for liver biopsy in some patients with hepatitis C. METHODS: We
attempted to validate the AAR by abstracting demographic and clinical data from a
database of consecutive patients with hepatitis C who had a liver biopsy between
1993 and 1998. We used definitions, methods of data collection, and analyses
comparable to those of the published study. A hepatopathologist blindly reviewed
49 liver biopsies for histological grade and stage. RESULTS: The current cohort
of 177 patients and the previous cohort of 139 patients were comparable in mean
age (42.3 vs 43.8 yr), percentage of men (63 vs 67), percentage with an AAR > or
=1 (20 vs 17), and Child-Pugh distribution, but differed in substantial use of
ethanol (11% vs 3.6%; p = 0.01) and in the prevalence of cirrhosis (23% vs 34%, p
= 0.06). Respective sensitivities of the AAR were 56% and 53%. An AAR > or =1 had
a positive predictive value of 64% (95% confidence interval 48-78%) for the
current cohort. Thirteen of 36 patients (36%) with an AAR > or =1 were
incorrectly identified as having cirrhosis. Of these 13 patients, 6 had a normal
AST and ALT, 5 had a minimally elevated AST or ALT, and 1 had advanced fibrosis
without cirrhosis. CONCLUSIONS: These results suggest that an AAR > or =1 may not
be as useful for predicting cirrhosis in chronic hepatitis C as previously
thought, and emphasizes the need for validation of clinical decision aids on
independent patient cohorts.
PMID- 11007238
TI - Oral budesonide in the treatment of primary sclerosing cholangitis.
AB - OBJECTIVE: This study was designed to evaluate the safety and estimate the
efficacy of oral budesonide in patients with primary sclerosing cholangitis
(PSC). METHODS: Twenty-one patients with PSC were treated with 9 mg daily of oral
budesonide for 1 yr. RESULTS: Significant, but marginally important, improvement
in serum alkaline phosphatase (1,235 +/- 190 vs 951 +/-206 U/L, p = 0.003) and
AST levels (119 +/- 14 vs 103 +/- 19 U/L, p = 0.02) was noted at the end of the
treatment period. Serum bilirubin levels increased significantly in the 18
patients who completed 1 yr of treatment (1.1 +/- 0.1 vs 1.4 +/- 0.3, p = 0.01)
and no significant changes in liver tests were noted 3 months after budesonide
was discontinued. The Mayo risk score did not change significantly, and although
a significant improvement in the degree of portal inflammation was noted at the
end of the treatment period, the degree of fibrosis and stage of disease were not
significantly affected. There was a marked loss of bone mass of the femoral neck
(0.851 +/- 0.02 vs 0.826 +/- 0.02 g/cm2, p = 0.002) and lumbar spine (1.042 +/-
0.02 vs 1.029 +/- 0.02 g/cm2, p = 0.09) at 1 yr of treatment with budesonide. Two
patients required evaluation for liver transplantation during treatment, and two
patients developed cosmetic side effects. CONCLUSIONS: Oral budesonide appears to
be of minimal, if any, benefit and it is associated with a significant worsening
of osteoporosis in patients with PSC.
PMID- 11007239
TI - A pilot study of pentoxifylline for the treatment of primary sclerosing
cholangitis.
AB - OBJECTIVE: There is no effective therapy for patients with primary sclerosing
cholangitis (PSC). Rats with experimental small bowel bacterial overgrowth
develop hepatobiliary injury similar to PSC. The hepatobiliary injury results
from peptidoglycan-polysaccharide-mediated activation of Kupffer cells, release
of cytokines such as tumor necrosis factor (TNF-alpha), and is prevented by
pentoxifylline. Our aims were to assess the safety and effects of pentoxifylline
on symptoms and biochemical liver tests in patients with PSC. METHODS: A total of
20 patients with clinical, cholangiographic, and histological features of PSC of
varying severity were treated with pentoxifylline sustained release (SR) tablets
(400 mg q.i.d.) for < or = 1 yr. Serum alkaline phosphatase, aspartate
aminotransferase, and bilirubin were monitored every 3 months for 1 year; serum
TNF-alpha and TNF receptor subtypes I and II were assessed at baseline and 1
year. RESULTS: Of 20 patients, 16 tolerated pentoxifylline and completed the
study. Two patients were withdrawn because of severe nausea, and two patients
were noncompliant with medication and withdrew. Pentoxifylline did not
significantly alter symptoms of fatigue or pruritus, serum liver tests, serum TNF
alpha or TNF receptor levels. CONCLUSIONS: In the current regimen, pentoxifylline
alone does not significantly improve symptoms or liver tests in patients with
PSC.
PMID- 11007240
TI - Bone density and metabolism in patients with viral hepatitis and cholestatic
liver diseases before and after liver transplantation.
AB - OBJECTIVE: Osteoporosis is frequently found in patients with cholestatic liver
disease (primary biliary cirrhosis/primary sclerosing cholangitis) and chronic
viral hepatitis. There is limited information about the long-term effect of liver
transplantation (OLT) on bone metabolism. The aim of this study was to
investigate the effect of liver transplantation on bone metabolism in patients
with cholestatic and viral liver diseases. METHODS: We randomly recruited 193
patients with chronic viral hepatitis or cholestatic liver diseases. Bone density
(Z-score) and markers of bone metabolism (intact parathyroid hormone [iPTH], PTH
70-84, osteocalcin, procollagen, telopeptide, and vitamin D) were determined
before and at time points (< and > 24 months) post-OLT. RESULTS: Before OLT, bone
density (Z-score) was decreased in patients with cholestatic (-1) and viral (
0.4) liver diseases. In both groups bone density continued to decrease in the
periods up to and more than 24 months after OLT. In the cholestatic group, bone
density decreased significantly compared to pre-OLT (p < 0.05) and to the viral
hepatitis group (p < 0,001). Markers of bone metabolism showed that after OLT,
bone metabolism was enhanced and shifted versus bone resorption.
Immunosuppressive drug therapy (glucocorticoids, cyclosporin, FK 506) directly
correlated with increased bone metabolism post-OLT. CONCLUSIONS: Bone loss is a
long-term problem after OLT, particularly in patients with cholestatic liver
diseases. Drug therapy is a main factor of bone loss. Pre- and post-OLT therapy
to reduce bone loss is recommended.
PMID- 11007241
TI - Changing pattern of esophageal cancer incidence in New Mexico.
AB - OBJECTIVE: Multiple reports indicate that esophageal adenocarcinoma incidence has
increased during the past 20 yr, especially in non-Hispanic white men. We
retrospectively reviewed adenocarcinoma and squamous cell carcinoma cases in our
heterogeneous state population to determine the effect of ethnicity on histology.
METHODS: We searched the New Mexico Tumor Registry for all cases of esophageal
cancer from 1973 to 1997. Inclusion criteria included histological diagnosis of
adenocarcinoma or squamous cell carcinoma, self-reported ethnicity, and gender.
Age-adjusted incidence rates for both adenocarcinoma or squamous cell carcinoma
were compared among ethnic groups in 5-yr intervals. RESULTS: Six hundred fifteen
patients met inclusion criteria. Esophageal adenocarcinoma age-adjusted incidence
rates/100,000 increased significantly during the 25-yr period: 1973-1977, 0.25
cases; 1978-1982, 0.33 cases; 1983-1987, 0.45 cases; 1988-1992, 0.85 cases; and
1993-1997, 1.19 cases; p < 0.001. In comparison, squamous cell carcinoma age
adjusted incidence rates did not increase significantly during the study period.
In non-Hispanic whites, the histological age-adjusted incidence rate changed
during the 1993-1997 period compared to other periods: 1993-1997, squamous cell
carcinoma 1.01 and adenocarcinoma 1.42, p < 0.001. In Hispanics, the age-adjusted
incidence rate of adenocarcinoma increased significantly in the fifth period
compared to other periods, p < 0.001. In all minority groups, squamous cell
carcinoma remained the predominant type. CONCLUSIONS: Esophageal adenocarcinoma
age-adjusted incidence increased in New Mexico from 1973 to 1997. This increase
was found in non-Hispanic whites and Hispanics and became predominant in non
Hispanic whites. Squamous cell carcinoma remains the primary type in minorities.
This study suggests that ethnicity may influence esophageal cancer histology or
ethnic background may place an individual at increased risk for certain types of
esophageal cancer.
PMID- 11007242
TI - Nonvariceal upper gastrointestinal bleeding: differences in outcome for patients
admitted to internal medicine and gastroenterological services.
AB - OBJECTIVE: It has been suggested that admission to a gastroenterology service
(GAS) is associated with a better prognosis and lower cost for treatment of
gastrointestinal (GI) diseases, such as upper GI bleeding (UGB). However, a large
potential bias by higher comorbidity on internal medicine services (MED) could
not be excluded from these studies. We therefore compared patients with upper GI
bleeding admitted to a gastroenterology or internal medicine department, with
special emphasis on prognostic factors, such as comorbidity, and outcome.
METHODS: Between 1991 and 1995, 322 patients were admitted to our hospital for
UGB. Forty-five patients had variceal and 277 patients had nonvariceal upper GI
bleeding (NUGB). Of 232 patients with primary NUGB, 125 were admitted to GAS and
93 to MED. The charts of these patients were revised, comorbidity was carefully
recorded, and the Rockall risk score was calculated. All deaths were individually
classified as unavoidable, mostly due to severe underlying illness, or
potentially avoidable. RESULTS: No differences in delay for endoscopy or
treatment were observed between GAS and MED. The rebleeding, surgery, and
mortality rates in GAS and MED patients were 11.6% versus 11.5% (NS), 7.8% versus
7.3% (NS), and 2.4% versus 10.8% (p = 0.02), respectively. Rockall scores
differed between GAS and MED patients (3.1 +/- 1.8 vs 3.7 +/- 1.7, p = 0.02). The
mortality rate stratified by Rockall score was lower for the GAS patients.
However, individual analysis revealed that only three of 13 deaths were
potentially avoidable: two of 10 at the MED and one of three at the GAS.
CONCLUSION: The lower mortality among nonvariceal upper GI bleeding patients
admitted to a gastroenterological service compared to an internal medicine
service was mainly due to lesser comorbidity. This effect was not detected by
stratification according to Rockall, but shown with analysis of individual
patient charts only. The latter underscores the potential pitfalls when comparing
outcome or cost of treatment between different medical services.
PMID- 11007243
TI - Pill silverer.
PMID- 11007244
TI - Microsporidial AIDS cholangiopathy due to Encephalitozoon intestinalis: case
report and review.
AB - Microsporidia are increasingly recognized as opportunistic infections in
immunodeficient patients, predominantly patients with AIDS. The two microsporidia
most commonly associated with disease in AIDS patients are Enterocytozoon
bieneusi and Encephalitozoon intestinalis (previously known as Septata
intestinalis). The most common clinical presentation of microsporidiosis in AIDS
patients is diarrhea, most commonly caused by the Enterocytozoon bieneusi
species. Encephalitozoon intestinalis is a recently described species that has
been reported to cause disseminated human infection including cholangitis. We
report a case of AIDS cholangiopathy that presented with abdominal pain and
cholestatic liver tests. Ultrasound examination and ERCP revealed a picture of
sclerosing cholangitis. Bile samples obtained at ERCP were negative for
microsporidia; stool studies for microsporidia and cryptosporidia were also
negative. No organisms were identified on routine light microscopy of the biopsy
specimens from the duodenum, ampulla, and bile duct. E. intestinalis spores were
demonstrated in the bile duct biopsies, by methylene blue and azure 11 staining
and confirmed by electron microscopy. Albendazole therapy was successful in
eradicating E. intestinalis with clinical improvement and improvement in CD4
count. However, the cholangiographic picture did not improve and repeat
cholangiography revealed progressive bile duct injury. Albendazole therapy was
delayed and may have been too late to prevent bile duct damage; the drug had to
be approved by the US Food and Drug Administration for compassionate use. This is
an unusual case of sclerosing cholangitis caused by an unusual organism and
requiring biliary sphincterotomy and stent placement for progressive stricturing
despite eradication of the infection.
PMID- 11007245
TI - Solitary pelvic nodule: diagnosis of metastatic prostate cancer by endoscopic
ultrasound-guided, fine-needle aspiration.
AB - Prostate cancer manifesting as an isolated perirectal mass is a rare occurrence.
The following is a report of a single pelvic nodule that was determined to be
metastatic prostate cancer by endoscopic ultrasound-guided, fine-needle
aspiration.
PMID- 11007246
TI - Liver biopsies in adult hemophiliacs with hepatitis C: a United States center's
experience.
AB - We report a case series of 13 adult hemophiliacs with serological evidence of
hepatitis C who underwent percutaneous liver biopsies without major
complications. We also briefly review the recent literature on safety of liver
biopsies in this population, and conclude that these patients may be safely
biopsied using appropriate precautions regardless of the severity of hemophilia.
PMID- 11007248
TI - Algorithm for the treatment of Crohn's disease: incorporation of emerging
therapies.
PMID- 11007247
TI - A case of primary hepatic lymphoma with hepatitis C liver cirrhosis.
AB - Primary hepatic lymphoma is rare. The usual type is a large-cell, high-grade
malignant B-cell lymphoma, although T-cell types have been described. Several
cases of primary hepatic lymphoma of B-cell origin developing in patients with
chronic hepatitis C virus infection have been reported. Recently, new findings
have raised the question of the induction of lymphoma by hepatitis C virus.
However, the causal relationship between hepatitis C viral infection and primary
hepatic lymphoma remains obscure. This article reports a case of histologically
proven primary hepatic lymphoma of T-cell origin, which was confined to the
liver, in the setting of hepatitis C liver cirrhosis. This association has not
previously been reported.
PMID- 11007249
TI - Further evolution of hepatitis C treatment: individualized therapy.
PMID- 11007250
TI - Re: Kilgore et al., The gastric cardia: fact or fiction?
PMID- 11007251
TI - 6MP for fathers with IBD at the time of conception: the value of a large clinical
experience over unrelated controls.
PMID- 11007252
TI - Successful nonsurgical treatment of primary mucosa-associated lymphoid tissue
lymphoma of colon presenting with multiple polypoid lesions.
PMID- 11007253
TI - New mutation in the hMSH2 gene in a Spanish Muir-Torre syndrome.
PMID- 11007254
TI - Whipple's disease: acquired resistance to trimethoprim-sulfamethoxazole.
PMID- 11007255
TI - Autoimmune pancreatitis and hepatitis: an uncommon association.
PMID- 11007256
TI - Prevention of pancreatitis by weekly amylase assay in patients with Crohn's
disease treated with azathioprine.
PMID- 11007257
TI - Frequency of thrombophilic abnormalities in Turkish children with inflammatory
bowel disease.
PMID- 11007258
TI - Severe anaphylactic reaction to infliximab: report of a case.
PMID- 11007259
TI - Primary biliary cirrhosis exacerbated by a course of acute hepatitis C and
subsequent interferon therapy.
PMID- 11007260
TI - Endoscopic stent pretzel.
PMID- 11007261
TI - Is the risk alkaline reflux a risk factor for laryngeal lesions?
PMID- 11007262
TI - Biochemical and virological changes in serum of nonresponder or relapser chronic
hepatitis C patients retreated with interferon and ribavirin followed by
interferon alone.
PMID- 11007263
TI - An unusual cause of massive gastric bleeding in a young patient.
PMID- 11007264
TI - Percutaneous microwave coagulation therapy for superficial hepatocellular
carcinoma on the liver surface.
PMID- 11007265
TI - Successful treatment of lymphoid follicular proctitis with sulfasalazine
suppositories.
PMID- 11007266
TI - Artificial ascites method: percutaneous treatments for hepatocellular carcinoma
located just beneath the diaphragm.
PMID- 11007267
TI - Transitory ischemic attack and acute hepatitis C.
PMID- 11007268
TI - Selective and facile cyclization of N-chloroacetylated peptides from the C4
domain of HIV Gp120 in LiCl/DMF solvent systems.
AB - Lithium salts have been reported to mediate the solubilization of peptides in
organic solvents in 1989 (Seebach, D., Thaler, A. & Beck, A. K. Helv. Chim. Acta
1989; 72, 857-867). The use of Li salts in an organic solvent to influence
cyclization of a reactive peptide that only polymerizes in an aqueous solvent,
has not been reported. Here, the selective and facile cyclization of N
chloroacetylated, C-cysteine amide peptides from the C4 domain of HIV-1 gp120 in
LiCl/DMF solvent systems is demonstrated. The addition of stoichiometric amounts
of Tris base to 1 mg/mL peptide in LiCl/DMF solutions was sufficient to drive the
cyclization to completion within 3 h at ambient temperatures. Cyclic peptides
were the only detectable reaction products and these were confirmed using
reversed-phase HPLC and mass spectrometric analyses of the final products. In
aqueous solutions at pH 7.4, only polymers were obtained as judged by HPLC and
SDS-PAGE. The method of using Li salts in an organic solvent to enhance the
cyclization of unprotected amphipathic peptides may be useful in many situations
beyond those described here.
PMID- 11007269
TI - Influence of the hydrophilic face on the folding ability and stability of alpha
helix bundles: relevance to the peptide catalytic activity.
AB - Although not the sole feature responsible, the packing of amino acid side chains
in the interior of proteins is known to contribute to protein conformational
specificity. While a number of amphipathic peptide sequences with optimized
hydrophobic domains has been designed to fold into a desired aggregation state,
the contribution of the amino acids located on the hydrophilic side of such
peptides to the final packing has not been investigated thoroughly. A set of self
aggregating 18-mer peptides designed previously to adopt a high level of alpha
helical conformation in benign buffer is used here to evaluate the effect of the
nature of the amino acids located on the hydrophilic face on the packing of a
four alpha-helical bundle. These peptides differ from one another by only one to
four amino acid mutations on the hydrophilic face of the helix and share the same
hydrophobic core. The secondary and tertiary structures in the presence or
absence of denaturants were determined by circular dichroism in the far- and near
UV regions, fluorescence and nuclear magnetic resonance spectroscopy. Significant
differences in folding ability, as well as chemical and thermal stabilities, were
found between the peptides studied. In particular, surface salt bridges may form
which would increase both the stability and extent of the tertiary structure of
the peptides. The structural behavior of the peptides may be related to their
ability to catalyze the decarboxylation of oxaloacetate, with peptides that have
a well-defined tertiary structure acting as true catalysts.
PMID- 11007270
TI - Solution conformational study of Scyliorhinin I analogues with conformational
constraints by two-dimensional NMR and theoretical conformational analysis.
AB - Two analogues of Scyliorhinin I (Scyl), a tachykinin with N-MeLeu in position 8
and a 1,5-disubstituted tetrazole ring between positions 7 and 8, introduced in
order to generate local conformational constraints, were synthesized using the
solid-phase method. Conformational studies in water and DMSO-d6 were performed on
these peptides using a combination of the two-dimensional NMR technique and
theoretical conformational analysis. The algorithm of conformational search
consisted of the following three stages: (i) extensive global conformational
analysis in order to find all low-energy conformations; (ii) calculation of the
NOE effects and vicinal coupling constants for each of the low energy
conformations; (iii) determining the statistical weights of these conformations
by means of a nonlinear least-squares procedure, in order to obtain the best fit
of the averaged simulated spectrum to the experimental one. In both solvents the
three-dimensional structure of the analogues studied can be interpreted only in
terms of an ensemble of multiple conformations. For [MeLeu8]Scyl, the C-terminal
6-10 fragment adopts more rigid structure than the N-terminal one. In the case of
the analogue with the tetrazole ring in DMSO-d6 the three-dimensional structure
is characterized by two dominant conformers with similar geometry of their
backbones. They superimpose especially well (RMSD = 0.28 A) in the 6-9 fragments.
All conformers calculated in both solvents superimpose in their C-terminal
fragments much better than those of the first analogue. The results obtained
indicate that the introduction of the tetrazole ring into the Scyl molecule
rigidifies its structure significantly more than that of MeLeu.
PMID- 11007271
TI - Structure-bioactivity of C-terminal pentapeptide of osteogenic growth peptide
[OGP(10-14)].
AB - The amino acid sequence of osteogenic growth peptide (OGP) consists of 14
residues identical to the C-terminal tail of histone H4. Native and synthetic OGP
are mitogenic to osteoblastic and fibroblastic cells and enhance osteogenesis and
hematopoiesis in vivo. The C-terminal truncated pentapeptide of OGP, H-Tyr-Gly
Phe-Gly-Gly-OH [OGP(10-14)], is a naturally occurring osteoblastic mitogen,
equipotent to OGP. The present study assesses the role of individual amino acid
residues and side chains in the OGP(10-14) mitogenic activity which showed a very
high correlation between osteoblastic and fibroblastic cell cultures. Truncation
of either Tyr10 or its replacement by Ala or D-Ala resulted in substantial, but
not complete, loss of activity. Nevertheless, only a small loss of activity was
observed following removal of the Tyr10 amino group. No further loss occurred
consequent to the monoiodination of desaminoTyr10 on meta-position. However, a
marked decrease in proliferative activity followed removal of the Tyr10 phenolic
or the Phe12 aromatic group. Loss of activity of a similar magnitude also
occurred subsequent to replacing Gly11 with L- or D-Ala. Approximately 50% loss
of mitogenic activity occurred subsequent to truncation of Gly14 or blocking the
C-terminal group as the methyl ester. All other modifications of the C-terminus
and L- or D-Ala substitution of Gly13 resulted in 70-97% decrease in activity.
Collectively, these data suggest that the integrity of the pharmacophores
presented by Tyr and Phe side chains, as well as the Gly residues at the C
terminus, are important for optimal bioactivity of OGP(10-14).
PMID- 11007272
TI - Chaperone-like activity of a synthetic peptide toward oxidized gamma-crystallin.
AB - alphaA-Crystallin can function like a molecular chaperone. We recently reported
that the alphaA-crystallin sequence, KFVIFLDVKHFSPEDLTVK (peptide-1, residues 70
88) by itself possesses chaperone-like (anti-aggregating) activity during a
thermal denaturation assay. Based on the above data we proposed that the peptide
1 sequence was the functional site in alphaA-crystallin. In this study we
investigated the specificity of peptide-1 against gamma-crystallin aggregation in
the presence of H2O2 and CuSO4. Peptide-1 was able to completely protect against
the oxidation-induced aggregation of gamma-crystallin. Removal of N-terminal Lys
or the replacement of Lys with Asp (DFVIFLDVKHFSPEDLTVK, peptide-2) did not alter
the anti-aggregation property of peptide-1. However, deletion of KF residues from
the N-terminus of peptide-1 resulted in a significant loss of its anti
aggregation property. Bio-gel P-30 size-exclusion chromatography of gamma
crystallin incubated with peptide-2 under oxidative conditions revealed that a
major portion of the peptide elutes in the void volume region along with gamma
crystallin, suggesting the binding of the peptide to the protein. Peptide-1 and
2 were also able to prevent the UV-induced aggregation of gamma-crystallin. These
data indicate that the same amino acid sequence in alphaA-crystallin is likely to
be responsible for suppressing the heat-denatured, oxidatively modified and UV
induced aggregation of proteins.
PMID- 11007273
TI - Reactivity toward deamidation of asparagine residues in beta-turn structures.
AB - Mimetics of beta-turn structures in proteins have been used to calibrate the
relative reactivities toward deamidation of asparagine residues in the two
central positions of a beta-turn and in a random coil. N-Acetyl-Asn-Gly-6
aminocaproic acid, an acyclic analog of a beta-turn mimic undergoes deamidation
of the asparaginyl residue through a succinimide intermediate to generate N
acetyl-Asp-N-Gly-6-aminocaproic acid (6-aminocaproic acid, hereafter Aca) and N
acetyl-L-iso-aspartyl (isoAsp)-Gly-Aca (pH 8.8, 37 degrees C) approximately 3
fold faster than does the cyclic beta-turn mimic cyclo-[L-Asn-Gly-Aca] with
asparagine at position 2 of the beta-turn. The latter compound, in turn,
undergoes deamidation approximately 30-fold faster than its positional isomer
cyclo-[Gly-Asn-Aca] with asparagine at position 3 of the beta-turn. Both cyclic
peptides assume predominantly beta-turn structures in solution, as demonstrated
by NMR and circular dichroism characterization. The open-chain compound and its
isomer N-acetyl-Gly-Asn-Aca assume predominantly random coil structures. The
latter isomer undergoes deamidation 2-fold slower than the former. Thus the order
of reactivity toward deamidation is: asparagine in a random coil approximately
3x(asparagine) in position 2 of a beta-turn approximately 30x (asparagine) in
position 3 of a beta-turn.
PMID- 11007274
TI - Structural study of the sodium channel inactivation gate peptide including an
isoleucine-phenylalanine-methionine motif and its analogous peptide
(phenylalanine/glutamine) in trifluoroethanol solutions and SDS micelles.
AB - In order to gain insight into the gating mechanisms of Na+ channels, in
particular their inactivation mechanisms, we studied the structures of the Na+
channel inactivation gate related peptide which includes the IFM (Ile-Phe-Met)
motif (Ac-KKKFGGQDIFMTEEQKK-NH2; K1480-K1496 in rat brain type-IIA Na+ channels,
MP-3A) and its F/Q(Gln) substituted one (MP-4A) in trifluoroethanol (TFE)
solutions and sodium dodecyl sulfate (SDS) micelles using circular dichroism (CD)
and 1H-NMR spectroscopies. Based on observed nuclear Overhauser effect
constraints, three-dimensional structures of MP-3A and MP-4A were determined
using simulated annealing molecular dynamics/ energy minimization calculations.
In TFE solutions, no appreciable differences in the structure were observed using
either CD or NMR spectra. In SDS micelles, however, the two peptides exhibited
definitely different structures from each other. It was found that in MP-3A,
residues 11488 and T1491 were spatially proximate with each other owing to
hydrogen bonding between the amide proton of 11488 and the hydroxyl oxygen atom
of T1491, whereas in MP-4A, F/Q substitution separated them owing to
conformational changes. The solvent-accessible surfaces calculated for the
structures of MP-3A and MP-4A showed that the former has a smoother interaction
surface to the hydrophobic docking site than the latter. In conclusion, the
conformational changes, as well as decreased hydrophobicity around the IFM motif
owing to the F/Q mutation, may be one reason why F1489Q mutated channels cannot
inactivate almost completely.
PMID- 11007275
TI - TBT--towards a better way to regulate pollutants.
PMID- 11007276
TI - Cost-benefit analysis of the use of TBT: the case for a treatment approach.
AB - The current climate of hostility towards the use of tributyltin (TBT) as an
active ingredient in ship anti-fouling paint appears to be based on a very biased
assessment of its environmental impact. While many national and international
regulatory agencies are moving towards further restriction, and a complete ban is
under active discussion, a number of factors appear to have been ignored. The
economic impact of a ban on TBT when no adequate substitute exists could be
substantial. Environmentally, consequences would include a substantial increase
in the consumption of fossil fuel, with corresponding increases in carbon dioxide
and sulphur dioxide emissions; the construction of more vessels; the transfer of
ship-building, ship-repairing and ship-breaking activities from well-regulated to
unregulated or under-regulated areas in the developing world; and a shift from
sea transport to less environmentally acceptable forms of transport. Experience
in Europe and other parts of the developed world shows that existing
restrictions, where they are properly enforced, are probably adequate to
alleviate the environmental damage associated with TBT. Some existing legislation
acts to inhibit the search for effective substitutes. The environmental benefits
of TBT have been ignored. Little thought has been given to a technical, rather
than a legislative solution to controlling TBT inputs to the environment. A
method is described for treating TBT-contaminated wastewaters, which has been
successfully tested in prototype at full scale. Legislative measures against TBT
will do nothing to address the problem of the existing backlog of contaminated
material, nor even to permit the IMO proposal for the removal of TBT from all
ships by 2008 to be successfully concluded in an environmentally safe manner,
since no provision has been made for the disposal of the existing TBT; most
probably it will be dumped in environmentally sensitive, unregulated areas in the
developing world.
PMID- 11007278
TI - The use of imposex to assess tributyltin contamination in coastal waters and open
seas.
AB - Imposex in muricid gastropods has been used to monitor tributyltin (TBT)
contamination worldwide. Pollution was severe during the 1980s but regulations
prohibiting the use of TBT-based antifoulants on vessels < 25 m in length have
been highly effective in reducing TBT levels in coastal waters. Large vessels are
still sources of TBT and major ports, especially those with dry docking and
repair facilities, continue to be hot-spots of contamination. Measures of imposex
suggest that severe pollution is normally localised to within a few kilometres of
them. Mild imposex, possibly as a result of TBT pollution (although other causes
have not been ruled out), has been described in whelks Buccinum undatum from
offshore waters of the southern and central North Sea. However, the species is
still abundant there and the occurrence of imposex does not seem to have affected
its breeding performance. Imposex was mild or absent in populations of dogwhelks
from open oceanic sites around the north Atlantic Ocean, suggesting that the
oceans are free of contamination at biologically significant levels.
PMID- 11007277
TI - A review of organotin regulatory strategies, pending actions, related costs and
benefits.
AB - Achieving consensus on equitable and effective national and global regulation(s)
for the use of organotins as biocides in antifouling boat bottom paints has
proven to be very complex and difficult for a variety of reasons as discussed in
this paper. There appears to be broad agreement among stakeholders about the
effectiveness of tributyltin (TBT) in antifouling paints. A draft Assembly
Resolution prepared by the Marine Environmental Protection Committee (MEPC) of
the International Maritime Organization (IMO) to propose a global ban on the use
of organotins in antifouling paints was approved by the IMO at its 21st regular
session (November 1999). In approving the Resolution, the Assembly agreed that a
legally binding instrument (global convention--an international treaty) be
developed by the Marine Environmental Protection Committee that should ensure by
1 January 2003, a ban on the application of tributyltin (TBT)-based antifouling
paints; and 1 January 2008 as the last date for having TBT-based antifouling
paint on a vessel. The Assembly also agreed that a diplomatic conference be held
in 2001 to consider adoption of the international legal instrument. Monitoring,
policing, enforcement, fines and record-keeping are yet to be defined. In
addition, the MEPC has also proposed that IMO promotes the use of environmentally
safe anti-fouling technologies to replace TBT. Existing national regulations in
the US and Europe have: (1) restricted the use of TBT in antifouling boat bottom
paints by vessel size (less than 25 m in length), thus eliminating TBT from the
smaller and recreational vessels that exist in shallow coastal waters where the
impacted oysters species grow; (2) restricted the release rates of TBT from co
polymer paints; and (3) eliminated the use of free TBT in paints. The present
movement toward a global ban suggests that the above regulatory approach has not
been sufficient in some countries. Advocates of the ban cite international
findings of: (1) higher levels of TBT in surface waters of ports and open waters;
(2) imposex still occurring and affecting a larger number of snail species; (3)
TBT bioaccumulation in selected fisheries; and (4) the availability of
'comparable' alternatives (to TBT) with less environmental impact. The global ban
has been absent of a policy debate on the: (1) lack of 'acceptable and approved'
alternatives in many nations; (2) appreciation of market forces in nations
without TBT regulations; (3) full consideration of the economic benefits from the
use of TBT; (4) 'acceptance' of environmental impacts in marinas, ports and
harbors; and (5) realization of the 'real' time period required by ships for
antifoulant protection (is 5-7 years necessary or desirable?). Estimates of fuel
savings range from $500 million to one billion. In assessing the environmental
impact from TBT, there are two sources: the shipyard painting vessels and the
painted vessel itself. Today vessels can be painted with regulated or banned
antifouling materials by boatyards in a country that does not have TBT
regulations and subsequently travel in international and regulated national
waters and thus bringing the impact back to the country which was trying to
prevent it. Worse, local and national regulations for TBT have proven to be the
antithesis of the popular environmental cliche--'Think Globally and Act Locally.'
Legislative policies enacted by 'regulated' countries to regulate the use of TBT
to protect (their) local marine resources have subsequently had far reaching
environmental and economic impacts which have in essence transferred TBT
contamination to those countries least able to deal with it. Market forces are
selective for cheap labor and cheap environments. 'Unregulated' countries have
unknowingly accepted the environmental and human health risks to gain the
economic benefits from painting TBT on ships. (ABSTRACT TRUNCATED)
PMID- 11007279
TI - Analytical aspects of the gas chromatographic determination of tributyltin and
metabolites in environmental samples.
AB - Tributyltin and its metabolites were determined in environmental samples by gas
chromatography using a flame photometric detection method. The analytical method
involved the propylation of the organotins and the use of a recovery standard to
correct for inefficient recovery. A detection limit of 5 ng Sn l(-1) for
seawater, and 5 ng Sn g(-1) for sediments, was obtained when the detector was
equipped with an optical filter; however, this concentration limit, which is
higher than the environmental quality standard for TBT, could be improved by a
factor of 100 on removing the filter. The limitations imposed by the choice of
recovery and internal standards were discussed and it was shown that the possible
presence of Sn(II) had no effect on the total extractable inorganic tin, as
determined by the analytical protocol. The identification of unexpected mixed
methylbutyltins in TBT-contaminated sediments was described, and the implications
of the existence of such compounds were discussed.
PMID- 11007280
TI - Evaluation of environmental levels and biological impact of TBT in Malta (central
Mediterranean).
AB - Chemical monitoring for butyltins in bulk seawater, surface microlayer and
superficial sediments determined that the two main local sources of marine
contamination by tributyltin (TBT) compounds in Malta are ship-repairing
dockyards and marinas. In bulk seawater, TBT values ranged from below the
detection limit of 5 ng Sn l(-1) to 300 ng Sn l(-1); in sediments derived from
the most polluted areas, TBT concentrations as high as 1500 ng Sn g(-1) were
measured. At TBT levels found in local harbours, several sublethal biological
responses are possible and were observed, including a significant reduction in
MFO enzyme system activities of fish; digestive cell atrophy in the oyster Ostrea
edulis; and induction of imposex in the snail Hexaplex trunculus. The latter two
responses are evident at TBT concentrations below the environmental quality
standard (20 ng TBT l(-1)). The ecological implications of these results are
discussed and it is concluded that exposure of marine organisms to TBT in local
harbours may be expected to lead to a reduction in the long-term survival of a
number of such organisms. For these reasons, both the use of TBT-based
antifouling paints for pleasure boats as well as drydock practices need to be
controlled by appropriate regulations and their enforcement.
PMID- 11007281
TI - Environmental impact of TBT: the French experience.
AB - The deleterious effects of TBT released by antifouling paints were first
documented in Arcachon Bay (France) at the end of the 1970s. As a result of the
high level of water contamination, the production of Pacific oysters was severely
affected by a complete lack of reproduction and the appearance of calcification
anomalies which were responsible for a strong decline in the marketable value of
the remaining stock. Regulations that had been successively adopted from January
1982 had positive effects on the recovery of the oyster grounds by reducing
ambient water concentrations. Most antifouling paints act by releasing toxicants
into the water which avoid the fixation of the organisms responsible for fouling.
The use of these paints results in significant inputs of biocides in the waters.
The harmful effects on non-target organisms were first evidenced in the bay of
Arcachon (France) where the most acute disturbances were recorded following
tributyltin (TBT) contamination.
PMID- 11007282
TI - Sea-nine antifoulant: an environmentally acceptable alternative to organotin
antifoulants.
AB - This article reviews previously reported data on the performance, environmental
fate, and environmental modeling of Sea-Nine 211 antifoulant (4,5-dichloro-2-n
octyl-4-isothiazolin-3-one). Since organotins are an industry standard, the
environmental fate and environmental modeling results of tributyltin (TBT) are
compared to those of the Sea-Nine antifoulant for reference. Laboratory and field
tests results have shown Sea-Nine antifoulant to be highly effective. Five years
of commercial use has confirmed this. Sea-Nine antifoulant and TBT were compared
in an environmental risk assessment to predict their effects on the environment.
Sea-Nine antifoulant was degraded rapidly in the environment by microorganisms.
Its half-life in aerobic and anaerobic microcosm studies was less than 1 h. TBT
degraded slowly under aerobic and anaerobic conditions with half-lives ranging
from 6 to 9 months. The degradation products of Sea-Nine antifoulant were ring
opened compounds with greatly reduced toxicity. TBT degraded to dibutyltin
species, which were still toxic and persistent in the environment.
Bioaccumulation studies in fish showed essentially no bioaccumulation of the Sea
Nine biocide. The bioaccumulation of TBT was significant, with bioconcentration
factors as high as 10000. The Sea-Nine antifoulant showed no chronic or
reproductive toxicity to marine species, while TBT showed a wide range of effects
on growth, development, and reproduction at levels as low as 2 parts per trillion
(ppt). Computer modeling using the Exposure Analysis Modeling System (EXAMS)
predicted maximum concentrations of Sea-Nine biocide of up to 10 ppt, far below
the maximum acceptable environmental concentration (MAEC) of 630 ppt. The maximum
predicted concentrations of TBT were as high as 345 ppt, far above the UK
Environmental Standard in seawater of 2 ppt.
PMID- 11007283
TI - The second order effects on commercial shipping of restrictions on the use of
TBT.
AB - Increased hull roughness reduces vessel speed and increases fuel consumption.
These are first order effects of restricting or prohibiting the use of
antifouling paints. Reduced transport capacity and increased capital costs are
frequently recognised as second order effects of such reductions in fleet
efficiency. This paper focuses on other second order effects of prohibiting or
restricting the use of TBT-based antifoulings. The potential cost increases will
affect high-speed vessels most severely. These vessels are the segment of the
shipping industry that is most relevant to the political drive in Europe towards
shifting the balance of transport of goods towards sea rather than road transport
for environmental reasons. Any decision to restrict or prohibit these paints
would tend also to induce a shift from local to global environmental problems,
which would be more difficult to manage.
PMID- 11007284
TI - Microbial interactions with tributyltin compounds: detoxification, accumulation,
and environmental fate.
AB - While inorganic forms of tin are of relatively low toxicity towards
microorganisms, the more lipid-soluble organotins can be highly toxic. Generally,
trisubstituted (R3SnX) organotins are more toxic than di- (R2SnX2) and
monosubstituted (RSnX3) compounds; the anion (X) apparently having little
influence on toxicity. However, many microorganisms exhibit resistance to
organotins, a phenomenon of relevance to the environmental cycling of organotins
and also to novel biological methods of treatment. Organotin degradation can
involve the sequential removal of organic moieties to yield less toxic
derivatives, e.g. debutylation of tributyltin compounds to di- and monobutylins.
Such degradation is known to take place in bacteria, algae and fungi, and this
provides one route for detoxification. In addition, microorganisms are capable of
accumulating tributyltin compounds, and this is another mechanism of removal from
solution. The high lipid solubility of organotins ensures cell penetration and
association with intracellular sites, while cell wall components also play an
important role. Of the fungal wall components, melanin pigments are capable of
TBT binding, and the addition of melanin to growing cultures can remove toxicity;
melanised strains are also more sensitive than albino strains of the same
species. To date, little attention has been paid to the biotechnological
exploitation of these interactions for the degradation of tributyltin or its
removal from solution. This paper describes some interactions of microorganisms
(bacteria, cyanobacteria, microalgae, and fungi) with tributyltin compounds, with
particular reference to toxicity, bioaccumulation and detoxification. Such
processes should receive due consideration in any environmental management
programme.
PMID- 11007285
TI - An alternative approach to antifouling based on analogues of natural processes.
AB - A number of marine organisms are able to resist fouling pressure and remain
essentially free of fouling. Some organisms are totally devoid of even the first
stages of biofilm formation involving bacteria and microalgae. A key feature in
recent research has been the realisation that previous low adherence technology
is an insufficient technical solution and that natural models, based on marine
and other organisms, incorporate other passive techniques for fouling resistance.
These characteristics may be incorporated into physical analogues of the natural
processes. This paper describes ways of producing physical analogues of some such
characteristics, the application of such techniques to surfaces in the marine
environment and the environmental impact. The paper includes some results of
recent trials and a cost comparison.
PMID- 11007286
TI - Leaching, runoff and speciation of arsenic in a laboratory mesocosm.
AB - Leaching and runoff of arsenic (As) from the contaminated soil of an old wood
impregnation plant, and fate in a recipient freshwater ecosystem, was studied in
soil-water-sediment mesocosms in laboratory (0.9 m3; total water volume 200 l).
During the 4-month experiment total leaching and discharge of As from regularly
irrigated soil was approximately 40 mg, i.e. approximately 0.6% of total initial
As content in the soil. Of the total As load, 7.5% remained in the water; 44%
settled down to the shallow (water depth 5-30 cm) sediment zone; and 48.5% to the
deeper (water depth 80 cm) sediment zone. The different arsenic species; arsenite
[As(III)], arsenate [As(V)], monomethylarsonic acid (MMAA) and dimethylarsinic
acid (DMAA), were analysed from irrigation and discharge water; mesocosm pool
water; and sediment pore water using ion chromatography-inductively coupled
plasma-mass spectrometry (IC-ICP-MS). The total amounts of arsenic in soil, water
and sediment were determined by ICP-MS. Arsenic was leached out from the soil as
As(V). In mesocosm water As(V) was the predominant dissolved species, but DMAA
and particle bound species, were also detected. In shallow sediment, As(V) was
the most abundant species together with some DMAA, whereas in deep sediment
As(III) was the dominant species.
PMID- 11007287
TI - Selective chemical extraction and grainsize normalisation for environmental
assessment of anoxic sediments: validation of an integrated procedure.
AB - An integrated selective extraction and size normalisation procedure for use in
metal partitioning and diagenetic studies of anoxic sediments and soils is
presented. Data obtained by this procedure can readily be combined with other
primary data (e.g. sulfur concentrations, carbonate concentrations, cation
exchange capacity, etc.) and derived parameters (e.g. degrees of pyritisation and
sulfidisation) that enhance interpretation of the behaviour of trace metals in
anoxic sediments. Achieving size normalisation during extraction, allows direct
comparison of sediments from dissimilar sedimentary environments, and simplifies
assessment of the processes that determine whether a sediment is a source of or a
sink for trace metals. Aspects of a study of trace metals in sediments from the
Brisbane River estuary, Australia, are used to illustrate applications of the
integrated procedure.
PMID- 11007288
TI - Long-term monitoring of arsenic and selenium species in contaminated groundwaters
by HPLC and HG-AAS.
AB - The long-term concentration and distribution of species of arsenic and selenium
in contaminated groundwaters from Kelheim was monitored. Most of the groundwater
wells contained elevated concentrations of iron, manganese and sulfur. Arsenic
(III), arsenic (V), selenium (IV) and selenium (VI) were separated using high
performance liquid chromatography (HPLC) based on phosphate buffers and collected
in fractions. Due to the complex matrix, the fractions were analyzed element
specifically by hydride-generating atomic absorption spectrometry (HG-AAS). The
combination of HPLC and HG-AAS was selected due to the authors' intention of
developing an easy-to-handle, but nonetheless reliable, method suitable for the
long-term monitoring of species distribution in an almost routine way, and taking
account of the threshold values of 10 microg/l for each element, indicated by
German drinking water regulations. To enhance the reliability of the method,
analytical quality control experiments were carried out. When applied to
groundwater wells from Kelheim (Germany) they revealed that arsenic (V) and
selenium (VI) were the dominating species. The presence of arsenic (III) and
selenium (IV) was assumed to be supported by organic matter.
PMID- 11007289
TI - Speciation of aluminium in forest soil extracts by size exclusion chromatography
with UV and ICP-AES detection and cation exchange fast protein liquid
chromatography with ETAAS detection.
AB - Aluminium speciation was studied in forest soil extracts by size exclusion
chromatography (SE) with UV and inductively coupled plasma-atomic emission
spectrometric (ICP-AES) detection and cation exchange fast protein liquid
chromatography (FPLC) with ETAAS detection. Size exclusion chromatography was
performed on a Superdex HR75 10/30 column. Isocratic clution with 0.15 mol dm(-3)
NaCl in TRIS-HCl buffer (pH = 5.5) was applied over 100 min at a flow rate of
0.35 cm(3) min(-1). The chromatographic run was followed at 278 nm and separated
Al species also determined 'off line' in 0.875 cm3 fractions by ICP-AES. The
analytical procedure enabled speciation of high molecular weight Al complexes.
Cation exchange FPLC was performed on a Mono S HR 5/5 column. Aqueous 8 mol dm(
3) NH4NO3 linear gradient elution was applied over 10 min at a flow rate of 1 cm3
min(-1). Separated Al species were collected in 0.5 cm3 fractions and Al
determined 'off line' by ETAAS. The analytical procedure enabled speciation of
some positively charged monomeric Al species. Negatively charged species were
eluted with the solvent front. The combination of the two analytical techniques
was successfully employed in speciation of Al in forest soil extracts. Water was
used as an extracting solution. It was found experimentally that 80-95% of Al in
aqueous extracts of forest soils exists in monomeric Al forms. Water soluble Al
(30-40%) is bound to high molecular weight complexes with humic substances. The
remaining monomeric Al in the low molecular weight fraction exists as AIF2+, Al
oxalate and Al-citrate species.
PMID- 11007290
TI - Phosphorus cycling through phosphine in paddy fields.
AB - Phosphine emission fluxes from paddy fields, phosphine ambient levels in air, and
the vertical profile of matrix-bound phosphine in soil have been measured
throughout the growing season of rice in Beijing, China. It was found that both
the seasonal and diurnal emission fluxes and ambient levels fluctuate
significantly. During the drainage period, phosphine released from the soil with
the highest diurnal average flux on the first period of drainage (approx. 17.7 ng
m(-2) h(-1)), whereas its highest ambient level (approx. 250 ng m(-3)) occurred
at 06.00 h. During the flooded period, phosphine emission was low, and the peaks
of phosphine emissions occurred at midnight. The average flux of PH3 emission for
the whole season was found to be approximately 1.78 ng m(-2) h(-1). The mass
fraction of matrix-bound phosphine is approximately 0.18 approximately 1.42 x 10(
7) (m/m) part of organic phosphorus or 3.4 approximately 9.2 x 10(-9) (m/m) part
of total phosphorus in paddy soil. The amount of phosphine emitted to the
atmosphere was only a small fraction of the phosphine that remained in the soil
in the matrix-bound form. Soil serves both as the source and the sink of PH3.
PMID- 11007291
TI - Nutrient elements of commercial tea from Nigeria by an instrumental neutron
activation analysis technique.
AB - A prototype miniature neutron source reactor (MNSR) with a thermal neutron flux
of 3.0 x 10(11) n cm(-2) s(-1) has been used to determine the concentrations of
some nutrient elements leading to short-lived activation products in commercial
tea leaf samples from Nigeria. A total of eight elements Al, Ca, Cl, Cu, K, Mg,
Mn and Na, that can be routinely used for quality control purposes, were analyzed
in this study. Two biological reference materials, tomato leaves (NIST-1573) and
citrus leaves (NIST-1572) were used as the standard and quality control
materials, respectively. The analytical results show that the average
concentrations of Al, Ca, Cl, Cu, K, Mg, Mn and Na in Nigerian tea are slightly
higher when compared with a Chinese herbal tea analyzed in this study. The
concentration ratios of K/Ca were found to be high in all the samples analyzed
suggesting cultivation in potash-rich soils.
PMID- 11007292
TI - Radiological consequences of Chernobyl accident: UN Scientific Committee on
Effects of Atomic Radiation confirms earlier IAEA assessments.
PMID- 11007293
TI - Navigation in biological and artificial systems.
PMID- 11007294
TI - How honeybees make grazing landings on flat surfaces.
AB - Freely flying bees were filmed as they landed on a flat, horizontal surface, to
investigate the underlying visuomotor control strategies. The results reveal that
(1) landing bees approach the surface at a relatively shallow descent angle; (2)
they tend to hold the angular velocity of the image of the surface constant as
they approach it; and (3) the instantaneous speed of descent is proportional to
the instantaneous forward speed. These characteristics reflect a surprisingly
simple and effective strategy for achieving a smooth landing, by which the
forward and descent speeds are automatically reduced as the surface is approached
and are both close to zero at touchdown. No explicit knowledge of flight speed or
height above the ground is necessary. A model of the control scheme is developed
and its predictions are verified. It is also shown that, during landing, the bee
decelerates continuously and in such a way as to keep the projected time to
touchdown constant as the surface is approached. The feasibility of this landing
strategy is demonstrated by implementation in a robotic gantry equipped with
vision.
PMID- 11007295
TI - Wide-field, motion-sensitive neurons and matched filters for optic flow fields.
AB - The receptive field organization of a class of visual interneurons in the fly
brain (vertical system, or VS neurons) shows a striking similarity to certain
self-motion-induced optic flow fields. The present study compares the measured
motion sensitivities of the VS neurons (Krapp et al. 1998) to a matched filter
model for optic flow fields generated by rotation or translation. The model
minimizes the variance of the filter output caused by noise and distance
variability between different scenes. To that end, prior knowledge about distance
and self-motion statistics is incorporated in the form of a "world model". We
show that a special case of the matched filter model is able to predict the local
motion sensitivities observed in some VS neurons. This suggests that their
receptive field organization enables the VS neurons to maintain a consistent
output when the same type of self-motion occurs in different situations.
PMID- 11007296
TI - Combined space-variant maps for optical-flow-based navigation.
AB - A robot navigating in an unstructured environment needs to avoid obstacles in its
way and determine free spaces through which it can safely pass. We present here a
set of optical-flow-based behaviors that allow a robot moving on a ground plane
to perform these tasks. The behaviors operate on a purposive representation of
the environment called the "virtual corridor" which is computed as follows: the
images captured by a forward-facing camera rigidly attached to the robot are
first remapped using a space-variant transformation. Then, optical flow is
computed from the remapped image stream. Finally, the virtual corridor is
extracted from the optical flow by applying simple but robust statistics. The
introduction of a space-variant image preprocessing stage is inspired by
biological sensory processing, where the projection and remapping of a sensory
input field onto higher-level cortical areas represents a central processing
mechanism. Such transformations lead to a significant data reduction, making real
time execution possible. Additionally, they serve to "re-present" the sensory
data in terms of ecologically relevant features, thereby simplifying the
interpretation by subsequent processing stages. In accordance with these
biological principles we have designed a space-variant image transformation,
called the polar sector map, which is ideally suited to the navigational task. We
have validated our design with simulations in synthetic environments and in
experiments with real robots.
PMID- 11007297
TI - The turn-back-and-look behaviour: bee versus robot.
AB - Honeybees and social wasps departing from a novel food source perform stereotype
flight manoeuvres, termed the turn-back-and-look behaviour (TBL). Based on
results of behavioural studies, it is proposed that the image motion generated by
the TBL provides the insect with information about the three-dimensional
structure of the goal's surroundings, thus enabling it to select reliable
landmarks that will guide it to the goal upon return. The colour, shape, and size
of landmarks, on the other hand, are learned mainly during arrival at the food
source. However, when bees are prevented from learning these cues on arrival,
they learn them during the TBL, despite the fact that this performance does not
require the use of image motion. A recently developed model shows that landmark
learning can indeed be accomplished during the TBL by exploiting cues others than
image motion. A mobile robot equipped with the appropriate software selects,
during the TBL, reliable marks and returns to the site of departure from
different locations by accomplishing image matching along a two-dimensional
vector field.
PMID- 11007298
TI - Insect visual homing strategies in a robot with analog processing.
AB - The visual homing abilities of insects can be explained by the snapshot
hypothesis. It asserts that an animal is guided to a previously visited location
by comparing the current view with a snapshot taken at that location. The average
landmark vector (ALV) model is a parsimonious navigation model based on the
snapshot hypothesis. According to this model, the target location is
unambiguously characterized by a signature vector extracted from the snapshot
image. This article provides threefold support for the ALV model by synthetic
modeling. First, it was shown that a mobile robot using the ALV model returns to
the target location with only small position errors. Second, the behavior of the
robot resembled the behavior of bees in some experiments. And third, the ALV
model was implemented on the robot in analog hardware. This adds validity to the
ALV model, since analog electronic circuits share a number of information
processing principles with biological nervous systems; the analog implementation
therefore provides suggestions for how visual homing abilities might be
implemented in the insect's brain.
PMID- 11007299
TI - How do insects use path integration for their navigation?
AB - We combine experimental findings on ants and bees, and build on earlier models,
to give an account of how these insects navigate using path integration, and how
path integration interacts with other modes of navigation. At the core of path
integration is an accumulator. This is set to an initial state at the nest and is
updated as the insect moves so that it always reports the insect's current
position relative to the nest. Navigation that uses path integration requires, in
addition, a way of storing states of the accumulator at significant places for
subsequent recall as goals, and a means of computing the direction to such goals.
We discuss three models of how path integration might be used for this process,
which we call vector navigation. Vector navigation is the principal means of
navigating over unfamiliar terrain, or when landmarks are unavailable. Under
other conditions, insects often navigate by landmarks, and ignore the output of
the vector navigation system. Landmark navigation does not interfere with the
updating of the accumulator. There is an interesting symmetry in the use of
landmarks and path integration. In the short term, vector navigation can be
independent of landmarks, and landmark navigation needs no assistance from path
integration. In the longer term, visual landmarks help keep path vector
navigation calibrated, and the learning of visual landmarks is guided by path
integration.
PMID- 11007300
TI - Triple-loop model of path control by head direction and place cells.
AB - Arthropods as well as mammals are able to return straight home after a random
search excursion under conditions that are designed to exclude all external cues.
After a brief clarification of the terminology, two principal systems of
information processing that can achieve this performance are introduced and
analysed: Polar versus Cartesian path integration. The different demands and
achievements of the two systems are confronted with neurophysiological findings
on the functioning of the hippocampus, and with a recent comprehensive model of
how the hippocampal place cells perform path integration. To connect the
neurophysiological findings with the behavior of the animal, a new model is
developed. It achieves three functionally diverse performances: maintenance and
control of a compass direction, navigation by path integration, and formation of
goals by connecting non-spatial features with their location. This is done by
three interconnected feedback loops, set by a common reference variable. Their
information-processing structure enables the animal not only to home but also to
go straight from any stored goal to any other, without explicit representation of
the distance between them, and without a topological arrangement of the store.
The model explains behaviors not yet understood and predicts still undiscovered
performances. Because it allows the isolation of orienting from storing functions
yet also shows how they can be connected, the model may help to reconcile
conflicting views on the function of the hippocampus.
PMID- 11007301
TI - Animat navigation using a cognitive graph.
AB - This article describes a computational model of the hippocampus that makes it
possible for a simulated rat to navigate in a continuous environment containing
obstacles. This model views the hippocampus as a "cognitive graph", that is, a
hetero-associative network that learns temporal sequences of visited places and
stores a topological representation of the environment. Calling upon place cells,
head direction cells, and "goal cells", it suggests a biologically plausible way
of exploiting such a spatial representation for navigation that does not require
complicated graph-search algorithms. Moreover, it permits "latent learning"
during exploration, that is, the building of a spatial representation without the
need of any reinforcement. When the rat occasionally discovers some rewarding
place it may wish to rejoin subsequently, it simply records within its cognitive
graph, through a series of goal and sub-goal cells, the direction in which to
move from any given start place. Accordingly, the model implements a simple
"place-recognition-triggered response" navigation strategy. Two implementations
of place cell management are studied in parallel. The first one associates place
cells with place fields that are given a priori and that are uniformly
distributed in the environment. The second one dynamically recruits place cells
as exploration proceeds and adjusts the density of such cells to the local
complexity of the environment. Both implementations lead to identical results.
The article ends with a few predictions about results to be expected in
experiments involving simultaneous recordings of multiple cells in the rat
hippocampus.
PMID- 11007302
TI - Spatial cognition and neuro-mimetic navigation: a model of hippocampal place cell
activity.
AB - A computational model of hippocampal activity during spatial cognition and
navigation tasks is presented. The spatial representation in our model of the rat
hippocampus is built on-line during exploration via two processing streams. An
allothetic vision-based representation is built by unsupervised Hebbian learning
extracting spatio-temporal properties of the environment from visual input. An
idiothetic representation is learned based on internal movement-related
information provided by path integration. On the level of the hippocampus,
allothetic and idiothetic representations are integrated to yield a stable
representation of the environment by a population of localized overlapping CA3
CA1 place fields. The hippocampal spatial representation is used as a basis for
goal-oriented spatial behavior. We focus on the neural pathway connecting the
hippocampus to the nucleus accumbens. Place cells drive a population of locomotor
action neurons in the nucleus accumbens. Reward-based learning is applied to map
place cell activity into action cell activity. The ensemble action cell activity
provides navigational maps to support spatial behavior. We present experimental
results obtained with a mobile Khepera robot.
PMID- 11007303
TI - Predictions derived from modelling the hippocampal role in navigation.
AB - A computational model of the lesion and single unit data from navigation in rats
is reviewed. The model uses external (visual) and internal (odometric)
information from the environment to drive the firing of simulated hippocampal
place cells. Constraints on the functional form of these inputs are drawn from
experiments using an environment of modifiable shape. The place cell
representation is used to guide navigation via the creation of a representation
of goal location via Hebbian modification of synaptic strengths. The model
includes consideration of the phase of firing of place cells with respect to the
theta rhythm of hippocampal EEG. A series of predictions for behavioural and
single-unit data in rats are derived from the input and output representations of
the model.
PMID- 11007304
TI - The endothelial surface layer.
AB - The endothelial lining of blood vessels presents a large surface area for
exchange of materials between blood and tissues, and is critically involved in
many other processes such as regulation of blood flow, inflammatory responses and
blood coagulation. It has long been known that the luminal surface of the
endothelium is lined with a glycocalyx, a layer of membrane-bound macromolecules
which has been determined by electron microscopy to be several tens of nanometers
thick. However, investigations in vivo have indicated the presence of a much
thicker endothelial surface layer (ESL), with an estimated thickness ranging from
0.5 microm to over 1 microm, that restricts the flow of plasma and can exclude
red blood cells and some macromolecular solutes. The evidence for the existence
of the ESL, hypotheses about its composition and biophysical properties, its
relevance to physiological processes, and its possible clinical implications are
considered in this review.
PMID- 11007305
TI - Na+/H+ and CI-/HCO3-antiporters of bovine pigmented ciliary epithelial cells.
AB - Medical therapy of glaucoma commonly aims at slowing aqueous humor formation by
the ocular ciliary epithelial bilayer, but underlying mechanisms are poorly
understood. The first step in secretion is NaCl uptake from the stroma into the
pigmented ciliary epithelial (PE) cell layer by electroneutral transporters.
After crossing gap junctions into the nonpigmented ciliary epithelial (NPE) cell
layer, solute is released into the aqueous humor. Published data have indicated
that both paired Na+/H+ and Cl-/HCO3- antiporters and the Na+-K+-2Cl- symporter
are involved in net uptake. The molecular identities of the paired antiporters
have not been elucidated. We have studied continuously cultured bovine PE cells.
Acid-activated 22Na+ uptake was inhibited by cariporide, EIPA (ethyl-isopropyl
amiloride) and amiloride, at concentrations characteristic of the NHE-1 isoform.
Videomicroscopy of BCECF-loaded PE cells verified the presence of an EIPA
inhibitable Na+/H+ antiporter. Removing external Cl- also triggered an
alkalinization, which was Na+-independent and could be inhibited by 4,4'
diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Application of hypotonicity
followed by return to isotonicity triggered a regulatory volume increase, which
was pharmacologically similar to the uptake mechanisms described for intact
rabbit ciliary epithelium. Reverse transcriptase polymerase chain reaction (RT
PCR) amplification of RNA from the human ciliary body detected expression of the
AE2 Cl-/HCO3- exchanger, but not of AE1, cAE3 or bAE3. Immunostaining of bovine
PE cells also revealed the presence of AE2 epitope. We conclude that paired NHE-1
Na+/H+ and AE2 Cl-/HCO3- antiporters are important components in the initial step
in aqueous humor formation.
PMID- 11007306
TI - Structural requirements for determining the substrate affinity of peptide
transporters PEPT1 and PEPT2.
AB - Peptide transporters PEPT1 and PEPT2 transport numerous compounds including small
peptides, peptide-like drugs and nonpeptidic compounds such as valacyclovir.
PEPT1 and PEPT2 show low and high affinity for most substrates, respectively, but
beta-lactam antibiotics without an alpha-amino group are the only known
substrates that prefer PEPT1 to PEPT2. The aim of this study was to compare the
recognition and affinity of various substrates between rat PEPT1 and rat PEPT2,
and to determine the structural requirements influencing the substrate affinity.
[14C]Glycylsarcosine uptake by PEPT1- or PEPT2-expressing transfectant was
inhibited by di- and tripeptides, but not by amino acids, tetrapeptides or most
cyclic dipeptides. All dipeptides and tripeptides examined showed more potent
inhibition of [14C]glycylsarcosine uptake via PEPT2 than via PEPT1, irrespective
of their charge and structure. Modification of the alpha-amino group of
dipeptides reduced their substrate affinity to both transporters, as compared to
unmodified dipeptides, but these dipeptides still showed potent inhibitory
effects on PEPT2. Among the nonpeptidic substrates tested, only the eight-amino
octanoic acid displayed stronger inhibition of [14C]glycylsarcosine uptake in
PEPT1 than in PEPT2. These findings suggest that alpha- or beta-amino carbonyl
function is the key structure responsible for the higher affinity for PEPT2 than
for PEPT1.
PMID- 11007307
TI - Differential calcium responses to the pituitary adenylate cyclase-activating
polypeptide (PACAP) in the five main cell types of rat anterior pituitary.
AB - We have compared the effects of pituitary adenylate cyclase-activating
polypeptide (PACAP-27) on the five main cell types of rat anterior pituitary in
primary culture by monitoring changes in cytosolic Ca2+ concentration ([Ca2+]i)
in single fura-2-loaded cells. Cells were typed by multiple sequential primary
immunocytochemistry at the end of the Ca2+ measurements. PACAP-27 increased
[Ca2+]i by three different mechanisms, each one dominant in a given cell type.
These involved Ca2+ entry or release from the stores and mediation through
different second messenger pathways: (1) stimulation of Ca2+ entry mediated by
cAMP was the main mechanism in somatotrophs; (2) Ca2+ release from the
intracellular Ca2+ stores mediated by phospholipase C (PLC) was the dominant
modality in gonadotrophs; (3) stimulation of Ca2+ entry not mediated by cAMP was
the main mechanism in lactotrophs. A minor fraction of somatotrophs (11%) may
also use mechanism 3. Corticotrophs and thyrotrophs exhibited weak responses to
PACAP (<10% of the cells responded), which in all cases were mediated by
mechanism 1. Mechanism 3 represents a novel effect of PACAP which cannot be
explained by interaction with the conventional PACAP receptor families.
PMID- 11007308
TI - The properties of the Kir6.1-6.2 tandem channel co-expressed with SUR2A.
AB - Functional ATP-sensitive K (KATP) channels have an octameric subunit structure
with four pore-forming subunits (Kir6.x) and four sulfonylurea receptors (SURx).
In the present study, the properties of the heteromeric KATP channel whose pore
subunits are composed of Kir6.1 and Kir6.2 were examined using a heterologous
expression system. In COS7 cells co-transfected with Kir6.1, Kir6.2 and SUR2A at
a ratio of 1:1:2, KATP channels showed various unitary conductances between those
of Kir6.1/SUR2A (33.6+/-4.2 pS) and Kir6.2/ SUR2A (67.1+/-1.6 pS). Kir6.1-6.2
tandem protein, constructed by fusing the C-terminus of Kir6.1 to the N-terminus
of Kir6.2 with a ten glutamine linker sequence, also formed a channel with an
intermediate conductance (58.9+/-1.5 pS). Kir6.2 and Kir6.1-6.2 showed similar
sensitivity to ATP4-: half-maximal inhibition (IC50) was obtained at 14.1+/-12.8
microM and 17.6+/-9.6 microM, respectively. In the presence of Mg2+, Kir6. 1-6.2
was significantly less sensitive than Kir6.2 to MgATP (IC50=95.5+/-49.6 microM
versus 18.9+/-5.0 microM). These results suggest that Kir6.1 and Kir6.2 are
endowed with the potential to form a heteromeric KATP channel, which has a low
sensitivity to MgATP.
PMID- 11007309
TI - Orexin A activates leptin-responsive neurons in the arcuate nucleus.
AB - Orexins, also named hypocretins, are newly described neuropeptides, which are
produced almost exclusively in neurons of the lateral hypothalamus and have been
shown to increase food intake after intracerebroventricular injection. Leptin,
the ob-gene product released from white adipocytes, is suspected to reduce food
intake mainly by acting on neurons in the arcuate nucleus of the hypothalamus.
Application of orexin A activated 85% (66 out of 78) of all neurons of the rat
arcuate nucleus investigated electrophysiologically in an in vitro slice
preparation, by a direct excitatory postsynaptic effect. Leptin inhibited
electrical activity in 10 out of 22 orexin-sensitive neurons in this brain region
and excited only 3 neurons. These data give the first indication as to where and
how orexin might interact with the leptin-responsive hypothalamic network.
PMID- 11007310
TI - Modulation of fetal and adult acetylcholine receptors by Ca2+ and Mg2+ at
developing mouse end-plates.
AB - It has long been known that extracellular Ca2+ and Mg2+ modulate synaptic
transmission at the neuromuscular junction, acting both pre- and post
synaptically. Relevant questions concerning the modulation of acetylcholine (ACh)
receptors (AChRs) are however still open: are the fetal (gamma-AChR) and adult
(epsilon-AChR) receptors modulated differently? Does the ACh concentration
influence the effect of divalent cations? Is the effect on channel open duration
dependent on type and concentration of divalent cation? These questions were
addressed by studying the modulation of the single-channel behaviour of gamma-
and epsilon-AChRs by Ca2+ and Mg2+ at the endplate of muscle fibres acutely
dissociated from 12- to 14-day-old mice. Ca2+ reduced the conductances of the two
receptor channels comparably. Mg2+ had a stronger effect than Ca2+ and reduced
the conductance of epsilon-AChR significantly more than that of gamma-AChR. With
0.1 microM ACh, Ca2+ and Mg2+ increased the mean open duration of gamma- and
epsilon-AChR channels comparably. At 100 microM ACh, gamma- and epsilon-AChR
channels opened in bursts of strikingly similar duration, which was unaffected by
divalent cations. These findings indicate that Ca2+, and even more so Mg2+, may
regulate synaptic transmission by modulating the function of AChRs in addition to
the well-established effects on transmitter release.
PMID- 11007311
TI - Nitric oxide uncouples gap junctions of supporting Deiters cells from Corti's
organ.
AB - Supporting cells of Corti's organ are electrically coupled via gap junctions.
They probably serve to maintain the unique cochlear environment that is required
for normal sensory function. In this study we used input capacitance measurements
under whole-cell voltage-clamp conditions to evaluate the effects of nitric oxide
on gap junctional communication between pairs of isolated supporting Deiters
cells. We show that the nitric oxide (NO) donor sodium nitroprusside causes the
uncoupling of Deiters cells, and that an NO synthase inhibitor blocks the effect.
The cGMP analogue 8-bromo-cGMP also uncouples Deiters cells. With either
treatment, the input capacitance of pairs of Deiters cells drops to single-cell
levels within minutes of application, indicative of electrical uncoupling. We
surmise that the NO/cGMP pathway may serve to modulate normal cochlear
homeostasis and possibly plays a role in ototoxic mechanisms.
PMID- 11007312
TI - Intracellular pH regulatory mechanism in a human renal proximal cell line (HKC
8): evidence for Na+/H+ exchanger, CI-/HCO3- exchanger and Na+-HCO3-
cotransporter.
AB - In the present study we investigated whether an immortalized human renal proximal
cell line, HKC-8, expresses a recently cloned Na+-HCO3- cotransporter (NBC-1)
and, if so, which isoform (kNBC-1 from kidney or pNBC-1 from pancreas) is
expressed in this cell line. Cell pH (pHi) measurements using a pH-sensitive
fluorescence probe in the absence of HCO3-/CO2 revealed the presence of a Na+/H+
exchanger that required high concentrations of amiloride for full inhibition. In
the presence of HCO3-/CO2 another pHi recovery process, dependent on Na+ but
independent of Cl-, was identified. This process was electrogenic and was
inhibited by 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulphonic acid (DIDS),
being consistent with the Na+-HCO3- cotransporter. In addition, the pHi responses
to Cl- removal were compatible with the presence of a Na+-independent Cl-/HCO3-
exchanger that was also inhibited by DIDS. Reverse transcriptase polymerase chain
reaction (RT-PCR) using primers designed for specific and common regions detected
mRNAs of both kNBC-1 and pNBC-1 and Western blot analysis confirmed the
expression of NBC-1 protein. These results indicate that HKC-8 has transport
activities similar to intact proximal tubules and also suggest that both kNBC-1
and pNBC-1 may contribute to the Na+-HCO3- cotransport activity in this cell
line.
PMID- 11007313
TI - Effect of glycolysis on pancreatic microcirculation and cellular functions in
anesthetized rats.
AB - It has been reported that aerobic glycolysis in the pancreas contributes less
than 10% to oxidative phosphorylation based on in vitro experiments using
pancreatic tissue segments. However, its contribution to aerobic glycolysis in
vivo remains uncertain. We investigated the effect of inhibiting glycolysis on O2
metabolism in microvessels, exocrine enzyme secretion, and the blood glucose
level in the pancreas of anesthetized rats in vivo. Inhibition of glycolysis, by
superfusing the pancreas of anesthetized rats with 2-deoxyglucose (10 mM) or
sodium fluoride (2 mM), significantly decreased O2 release from erythrocytes
flowing in the microvessels by 30-40%. Inhibiting glycolysis did not affect the
exocrine secretion of pancreatic juice but decreased the secretion of total
protein by approximately or = to 40%. Inhibiting glycolysis decreased blood
glucose levels by approximately or = to 40% and increased glucagon release
twofold. Aerobic glycolysis may play more important roles in the regulation of
O2, metabolism, pancreatic exocrine enzyme secretion and the blood glucose level
in rat pancreas.
PMID- 11007314
TI - Hypoxia and fatigue-induced modification of function and proteins in intact and
skinned murine diaphragm muscle.
AB - Fatigue studies of isolated, intact muscles typically utilize solutions saturated
with O2. However, under in vivo fatiguing conditions, less oxygen is delivered to
the muscles and they actually experience hypoxia. No studies to date have
correlated the effects of acute hypoxia on the isometric contractile properties
of intact muscles, skinned fibers isolated from the same muscles, and the
cellular content of specific muscle proteins. Therefore, we have studied the
effects of in vitro acute hypoxia on the fatigability of intact diaphragm muscle
strips and on the isometric contractile properties of single Triton-skinned
fibers isolated from control and hypoxic diaphragm muscles. We found that hypoxia
and fatiguing stimulation per se affect the tetanic force of intact muscle strips
without exhibiting any significant deleterious effects on the calcium-activated
force of skinned muscle fibers dissected from the intact muscles. In contrast,
fatiguing stimulation under hypoxic conditions decreased both the tetanic force
of muscle strips and the calcium-activated force of skinned muscle fibers. Gel
electrophoresis of muscles subjected to hypoxia and hypoxic-fatigue revealed that
there is a significant reduction in three protein bands when compared to control
muscles. Protein modification may be the underlying mechanism of muscle fatigue
under physiologic conditions.
PMID- 11007315
TI - Na/K pump alpha subunit expression in rabbit ventricle and regional variations of
intracellular sodium regulation.
AB - We examined the isoform distribution and expression of the alpha subunit of the
Na/K-ATPase in the left ventricular muscle of rabbit heart in order to determine
whether previously reported regional differences in intracellular sodium
regulation derive from differences in pump expression. Immunohistochemical
techniques show that only the alpha1 isoform is present in rabbit ventricle;
therefore, regional variation in isoform distribution is not possible. Western
blots of samples taken from subendocardial and sub-epicardial regions confirm the
absence of alpha2 and alpha3 isoforms but also show that levels of the alpha1
isoform do not differ significantly in the two regions. The ratio of
densitometric readings from blot bands was 1.18+/-0.17 (epicardial:endocardial;
mean +/-SEM). Measurements of fully activated pump current in voltage-clamped
cells were achieved by dialysing the cell via the patch pipette with 50 mM Na and
applying 1 mM dihydroouabain. The current measured was 0.16+/-0.02 pA/pF in
epicardial cells and 0.17+/-0.02 pA/pF in endocardial cells. These results
indicate that the capacity of cells from the two regions to generate sodium
efflux is identical. Regional differences in intracellular sodium regulation,
therefore, are more likely to arise from differences in influx of sodium.
PMID- 11007316
TI - Cs+ block of the cardiac muscarinic K+ channel, GIRK1/GIRK4, is not dependent on
the aspartate residue at position 173.
AB - Cs+ block of GIRK1/GIRK4 expressed in Xenopus oocytes has been investigated. It
has been reported that a negatively charged aspartate residue at position 172 in
IRK1 is responsible for Cs+ block of the channel. IRK1, a homotetramer, has four
aspartate residues at this position. GIRK1/GIRK4 is a heterotetramer and has two
aspartate residues at the equivalent position (GIRK1-D173) and, consequently, it
should be less sensitive to Cs+. Cs+ caused voltage-dependent block of
GIRK1/GIRK4 current (measured with the two-microelectrode voltage-clamp
technique). The apparent fraction of the electrical field through which Cs+ moves
in order to reach its site of block (delta approximately equals 1.66) is
comparable to that in IRK1, suggesting that Cs+ binds to a similar site in the
two channels. GIRK1/GIRK4 was less sensitive than IRK1 to Cs+ -the Kd was 3.0-8.5
times greater and at potentials more negative than approximately or = to 130 mV
there was voltage-dependent relief of block of GIRK1/GIRK4 (not the case with
IRK1). However, the mutations GIRK1-D173A and GIRK1-D173Q increased the
sensitivity of the channel to Cs+, while adding a negatively charged aspartate
residue to GIRK4 at the equivalent position (GIRK4-N 79D) decreased Cs+
sensitivity. GIRK1-D173 cannot be the site of Cs+ block of GIRK1/GIRK4.
PMID- 11007317
TI - Changes in the Ca2+-activation characteristics of demembranated rat single muscle
fibres after prolonged incubation at room temperature in the presence and absence
of DTT and protease inhibitors.
AB - Prolonged incubation (24 h) of chemically skinned rat muscle preparations in
rigor solutions at room temperature and in the absence of reducing agents and
protease inhibitors modified the Ca2+-activation characteristics of the
contractile machinery. In the absence of reducing agents and protease inhibitors,
the contraction threshold for incubated fibres was shifted to lower Ca2+
concentrations and the steepness of the steady-state force-pCa (-log10)[Ca2+])
curve was decreased compared to that of control muscle fibres. Mean myosin ATPase
activity under these conditions was significantly lowered by a factor of 2.7.
Fibres incubated in the presence of 10 mM dithiothreitol (DTT) and protease
inhibitors (100 microM pepstatin A/200 microM leupeptin) produced a maximum Ca2+
activated force per cross-sectional area that compared favourably with that of
freshly dissected muscle fibres and there were no changes in the other
contractile activation characteristics. Intermediate responses were obtained when
fibres were incubated in the presence of either DTT or protease inhibitors.
MgATPase activities of incubated preparations increased significantly following
the addition of protease inhibitors and/or DTT to the incubation medium. Taken
together, these results suggest that in the presence of DTT and protease
inhibitors, most contractile properties are maintained at levels seen in fresh
mechanically skinned fibres. The extended viability of this preparation and its
closely related properties with fresh muscle fibres make it a useful model for
experiments requiring longer term incubations with biological agents.
PMID- 11007318
TI - Volume-sensitive KCI cotransport associated with human cervical carcinogenesis.
AB - This study investigates the volume-sensitive KCI cotransporter (KCC) in various
types of human cervical epithelial cell, testing the hypothesis that cervical
malignancy is accompanied by differential expression of volume-sensitive KCC.
Normal human cervical epithelial cells have KCCs which are quiescent in normal
physiological conditions and are relatively refractory to hypotonic stress. By
contrast, cervical cancer cells have KCCs which are also nearly quiescent in
normal physiological conditions but high transport rates are observed in response
to hypotonic challenge. Using isoform-specific primers, mRNA transcripts of KCC1,
KCC3 and KCC4 were identified by reverse transcriptase polymerase chain reaction
(RT-PCR) in several types of cervical cell, and confirmed by digestion with
specific restriction endonucleases. By semiquantitative RT-PCR with beta-actin as
the internal standard, the results indicate that cervical carcinogenesis is
accompanied by the up-regulation of mRNA transcripts in KCC1, KCC3 and KCC4.
[(Dihydroindenyl)oxy] alkanoic acid (DIOA), a KCC inhibitor, blocked both the
regulatory volume decrease (RVD) process and volume-sensitive 86Rb+ efflux from
cervical cancer cells in a dose-dependent manner. The volume-sensitive 86Rb+
efflux from cervical cancer cells was also blocked by two protein phosphatase
inhibitors, calyculin A and okadaic acid, with IC50 values of 0.8 and 6 nM,
respectively. Conversely, protein kinase inhibitors, chelerythrine and
staurosporine, increased Cl- dependent 86Rb+ efflux. NEM (1 mM) led to a fivefold
stimulation of 86Rb+ efflux which was totally Cl- dependent in cervical cancer
cells. Hypotonicity could not stimulate any further 86Rb+ efflux after NEM
treatment. These results indicate that the volume-sensitive KCC in cervical
cancer cells plays a significant role in volume regulation and that the
activities are modulated by a phosphorylation cascade. Taken together with our
previous studies, we suggest the volume-regulatory ion channels and the co
transport systems work synergistically for volume regulation in human cervical
cancer cells.
PMID- 11007319
TI - Ornithine metabolism along the female mouse nephron: localization of ornithine
decarboxylase and ornithine aminotransferase.
AB - The fate of ornithine in the nephron of the female OF-1 Swiss mouse remains
unknown. The aim of the present study was to identify the nephron segments
containing the key enzymes involved in ornithine metabolism: ornithine
decarboxylase (ODC) and ornithine aminotransferase (OAT). Viable tubules isolated
by microdissection were incubated with [1-14C]ornithine to study the oxidative
pathway. Other tubules were permeabilized to measure the ODC activity. Ornithine
was decarboxylated in all intact tubules. Gabaculine, a suicide inhibitor of OAT,
and rotenone sharply decreased the production of 14CO2 from [1-14C]ornithine. No
ODC activity was found in permeabilized tubules isolated from untreated mice.
Testosterone increased ODC activity in the proximal tubule substantially and to a
minor extent in other nephron segments. In situ hybridization showed ODC
messenger ribonucleic acid (mRNA) to be absent in kidneys of untreated females
but abundant in the cortex and the outer stripe of the outer medulla of
testosterone-treated female mice. The whole proximal tubule contained a great
density of silver grains corresponding to ODC mRNA. In conclusion, no basal ODC
activity was found in the nephron of female mice. The testosterone-inducible ODC
is localized mainly in the proximal tubule, but is also present in distal tubules
and collecting ducts. OAT is distributed along the whole nephron, but its
activity is higher in proximal tubules than in distal tubules.
PMID- 11007320
TI - Potassium efflux triggered by P2Y purinoceptor activation in cultured pituicytes.
AB - We have previously investigated the effects of extracellular ATP on the
concentration of free cytosolic calcium ([Ca2+]i) from rat cultured
neurohypophysial astrocytes (pituicytes). We demonstrated that ATP acts via a P2Y
receptor to increase [Ca2+]i. In the present study, we examine the effect of ATP
on K+ efflux using 86Rb+ as an isotopic tracer, in order to characterize the
possible presence of a Ca2+-activated K+ conductance and to establish the
implications of pituicytes in the regulation of stimulus-secretion coupling. ATP
evoked an increase in 86Rb+ efflux from cultured pituicytes. This effect was Ca2+
dependent, as indicated by the unresponsiveness of cells loaded with BAPTA/AM (20
microM). Furthermore, the effect of ATP was mimicked by 2-methylthio-adenosine-5'
triphosphate (2MeSATP), a P2 purinoceptor agonist, and abolished by Reactive Blue
2 (RB-2), a selective P2Y antagonist, implying a role for the P2Y purinoreceptor.
A pharmacological study revealed that Ba2+ and tetraethylammonium (TEA), two
inhibitors of K+ channels, both strongly reduced the ATP-stimulated 86Rb+ efflux.
In addition, the effect of ATP was modulated by different peptidic toxins. Apamin
(100 nM), an inhibitor of the small-conductance Ca2+-activated K+ channels,
partly blocked ATP-induced 86Rb+ efflux. Leiurus quinquestriatus hebraeus (LQH)
scorpion venom (20 microg/ml) and Buthus tamulus (BT) scorpion venom (20-200
microg/ml) inhibited ATP-induced 86Rb+ efflux. The specificity of the effects of
the crude venoms was checked using charybdotoxin (100 nM) and iberiotoxin (1 pM),
which are the active toxins extracted from the LQH and BT venoms, respectively.
These data indicate the involvement of several types of Ca2+-activated K+
channels in the ATP-dependent K+ efflux, and lead to the proposal that, in the
neurohypophysis, extracellular ATP released by nerve terminals may act directly
on the pituicytes and induce a K+ efflux via a P2Y purinoreceptor.
PMID- 11007321
TI - Determinants of the difference between expired and core temperatures: effect of a
breath-hold.
AB - After a 30-s breath-hold (BH), expired temperature (TE) does not reach core
temperature. One explanation is that the gas in the airways is not in thermal
equilibrium with the airway walls. This possibility was eliminated by comparing
TE in six subjects breathing either helium-oxygen or air after a BH. Another
possibility is that the airway walls and surrounding tissues have sufficient
thermal inertia to slow down thermal equilibrium during BH. This was checked by
measuring oral and upper esophageal temperatures after cooling or heating the
airways. It took more than 2 min for these temperatures to recover their steady
state value. Six subjects were requested to perform a long apnea after
hyperventilating for 1 min and then taking a single breath of 100% oxygen. TE was
still lower than core temperature after a 1-min BH, and there was no difference
after a 2-min BH. The difference between expired and core temperatures during BH
thus appears to be due to the thermal inertia of the airways and their
surrounding tissues.
PMID- 11007322
TI - Modulation of a cloned human A-type voltage-gated potassium channel (hKv1.4) by
the protein tyrosine kinase inhibitor genistein.
AB - A cloned, human, A-type, voltage-gated potassium channel (hKv1.4) was expressed
transiently in Chinese hamster ovary cells and the effects of the broad-spectrum
tyrosine kinase inhibitor genistein on hKv1.4 were studied using the whole-cell
patch-clamp recording method. Genistein (up to 50 microM) reversibly reduced the
peak currents of hKv1.4 by 44.9+/-12%. In addition, genistein markedly slowed the
activation kinetics (time constant tau(a)) of hKv1.4. At +50 mV, tau(a) increased
from 1.8+/-0.3 to 5.0+/-0.6 ms (P<0.01). The effect of genistein on the channel
inactivation kinetics (time constant tau(i)) was more complex, in that tau(i) was
increased significantly at lower step potentials but unaltered at +50 mV or more
depolarized potentials. Tail current analysis showed that genistein had no effect
on the kinetics of deactivation (time constant tau(d)), but shifted the steady
state activation curve significantly to the right by about 15 mV (potential for
half-maximal activation, V1/2, changed from -7.4+/-4.4 to +7.7+/-2.7 mV) with a
moderate change in the slope (k) of the curve (from 17.4+/-2.2 to 23+/-1.0 mV,
P<0.05). Genistein slightly altered the slope of the steady-state inactivation
curve from -5.5+/-0.4 to -7.5+/-0.4 mV (P<0.01). The recovery rate from
inactivation was not altered by genistein. The tyrosine phosphatase inhibitor
orthovanadate (1 mM) alone had little impact on current amplitude or channel
kinetics. However, orthovanadate significantly, but not completely, blocked the
effect of genistein on current amplitude (by 25.5%) and kinetics (by 67.1%).
Daidzein (up to 50 microM), an inactive analogue of genistein, had no effect on
current amplitude or kinetics. In contrast to genistein, another tyrosine kinase
inhibitor, herbimycin A, had little effect on the channel peak amplitude or
kinetics. In addition, genistein had a similar impact on the channel peak current
amplitude and kinetics in cells with or without pre-treatment with herbimycin A
(10 microM). The data suggest that genistein-induced inhibition of tyrosine
phosphorylation may not be the exclusive mechanism by which hKv1.4 is down
regulated and channel gating affected. Genistein may produce a non-catalytic
blockade of this channel.
PMID- 11007324
TI - A new arthropod from the Silurian Konservat-Lagerstatte of Herefordshire, UK.
AB - A small, non-biomineralized, macrophagous arthropod with chelicerate affinities,
Offacolus kingi gen. et sp. nov., from the Silurian (Wenlock Series) of
Herefordshire, UK, is described. The dorsal exoskeleton comprises an arch-like
cephalic shield, a thorax of three free tergites and a triangular posterior tagma
of five fused tergites, the last with a stout postero-dorsally directed medial
spine. Seven pairs of appendages beneath the cephalic shield surround a postero
medially sited oral cavity on the ventral surface of the head. Appendages I and,
probably II are uniramous and project antero-ventrally; I was sensory and II
sensory and/or ambulatory. Appendages III-VI are biramous, each with an antero
ventrally projecting ramus and a robust, highly geniculate, horizontally oriented
ramus that projects through an anterior gape. The former rami were ambulatory and
the latter have spinose terminal podomeres and functioned as a unit for trapping
food and transferring it towards the oral cavity. Appendage VII, which is
probably uniramous, is posteroventrally directed and flap like. Each tergite of
the thorax and posterior tagma covers at least a pair (probably two pairs) of
probably biramous appendages with each ramus flap like and setose.
PMID- 11007323
TI - Evolutionary novelties in islands: Drosophila santomea, a new melanogaster sister
species from Sao Tome.
AB - The finding of new melanogaster sister species may help us in understanding more
about how the emergence of genetic novelties, particularly in insular habitats,
can result in speciation. Here we report on the discovery of Drosophila santomea,
which is the first melanogaster sibling found off West-equatorial Africa, on Sao
Tome, one of the Gulf of Guinea islands. Although the eight other melanogaster
sister species are remarkably conservative in their morphology except for their
terminalia, the new find has a morphological trait distinguishing it from all of
these: a pure yellow body coloration of both sexes without the normal black
abdominal banding. Evidence from the terminalia, polytene and mitotic
chromosomes, period gene and allozymes are provided indicating that it is
nonetheless the nearest relative of Drosophila yakuba with which it coexists on
the island. The new find is a clear-cut taxon as shown by the production of
sterile male hybrids, eventually with developmental defects, in both directions
of cross with yakuba and by the existence of an altitudinal divide accompanied by
a hybrid zone at mid-elevation on the island. Molecular and karyotypic data
further support this conclusion. In contrast to the significant divergence of
their nuclear DNAs, an intriguing similarity in their cytochrome b sequences was
observed indicating a recent coalescence common to santomea, yakuba and also
teissieri cytoplasms. These were shown to harbour the same Wolbachia
endosymbiotic bacteria which could possibly be responsible for mitochondrial DNA
hitchhiking across the species barrier.
PMID- 11007325
TI - Non-random dispersal in the butterfly Maniola jurtina: implications for
metapopulation models.
AB - The dispersal patterns of animals are important in metapopulation ecology because
they affect the dynamics and survival of populations. Theoretical models assume
random dispersal but little is known in practice about the dispersal behaviour of
individual animals or the strategy by which dispersers locate distant habitat
patches. In the present study, we released individual meadow brown butterflies
(Maniola jurtina) in a non-habitat and investigated their ability to return to a
suitable habitat. The results provided three reasons for supposing that meadow
brown butterflies do not seek habitat by means of random flight. First, when
released within the range of their normal dispersal distances, the butterflies
orientated towards suitable habitat at a higher rate than expected at random.
Second, when released at larger distances from their habitat, they used a non
random, systematic, search strategy in which they flew in loops around the
release point and returned periodically to it. Third, butterflies returned to a
familiar habitat patch rather than a non-familiar one when given a choice. If
dispersers actively orientate towards or search systematically for distant
habitat, this may be problematic for existing metapopulation models, including
models of the evolution of dispersal rates in metapopulations.
PMID- 11007326
TI - Developmental trade-offs and life histories: strategic allocation of resources in
caddis flies.
AB - Resource allocation trade-offs during development are potentially very important
in the evolution of organism morphology and life-history strategy However, they
have rarely been demonstrated empirically. To what extent the division of limited
resources between growing organs is a consequence of particular developmental
pathways or varies strategically in line with life-history predictions is
unknown. It has been demonstrated in a number of holometabolous insects that
altering the resources available at pupation changes the pattern of allocation to
adult tissues, but this has not been examined in a life-history context. Using
caddis flies (Trichoptera), we show here that the effect of depleted larval
resources on the pattern of somatic and reproductive investment is not fixed but
varies between species with different life-history patterns. In particular, we
demonstrate that, in a long-lived species, thorax size is preserved, which
contrasts with the pattern previously observed in a short-lived species. That the
adult body can be differentially altered by the same resource depletion in the
larvae demonstrates that the allocation of resources amongst body parts is not a
consequence of fixed pathways during development. Rather, the allocation of
resources during development can occur in a manner consistent with the
minimization of the effects on adult fitness.
PMID- 11007327
TI - Lifetime success and interactions of farm salmon invading a native population.
AB - Farm Atlantic salmon escape and invade rivers throughout the North Atlantic
annually, which has generated growing concern about their impacts on native
salmon populations. A large-scale experiment was therefore undertaken in order to
quantify the lifetime success and interactions of farm salmon invading a
Norwegian river. Sexually mature farm and native salmon were genetically
screened, radio tagged and released into the River Imsa where no other salmon had
been allowed to ascend. The farm fishes were competitively and reproductively
inferior, achieving less than one-third the breeding success of the native
fishes. Moreover, this inferiority was sex biased, being more pronounced in farm
males than females, resulting in the principal route of gene flow involving
native males mating with farm females. There were also indications of selection
against farm genotypes during early survival but not thereafter. However,
evidence of resource competition and competitive displacement existed as the
productivity of the native population was depressed by more than 30%. Ultimately,
the lifetime reproductive success (adult to adult) of the farm fishes was 16%
that of the native salmon. Our results indicate that such annual invasions have
the potential for impacting on population productivity, disrupting local
adaptations and reducing the genetic diversity of wild salmon populations.
PMID- 11007328
TI - Differential effects of endoparasitism on the expression of carotenoid- and
melanin-based ornamental coloration.
AB - The striking diversity of sexual dimorphisms in nature begs the question: Why are
there so many signal types? One possibility is that ornamental traits convey
different sets of information about the quality of the sender to the receiver.
The colourful, pigmented feathers of male birds seem to meet the predictions of
this hypothesis. Evidence suggests that carotenoid pigmentation reflects the
nutritional condition of males during moult, whereas in many instances melanin
pigmentation is a reliable indicator of social status. However, as of yet there
have been no experimental tests to determine how these two ornament types respond
to the same form of environmental stress. In this study, we tested the effect of
endoparasitic infection by intestinal coccidians (Isospora sp.) on the expression
of both carotenoid- and melanin-based ornamental coloration in captive male
American goldfinches (Carduelis tristis). We found that the carotenoid-based
plumage and bill coloration of parasitized males was less saturated than that
developed by unparasitized males, but that the brightness and size of melanin
based black caps did not differ between the groups. These findings provide the
most robust empirical support to date for the notion that carotenoid and melanin
ornaments reveal different information to conspecifics.
PMID- 11007329
TI - Androgen levels and female social dominance in Lemur catta.
AB - Morphological and behavioural traits which improve agonistic power are subject to
intrasexual selection and, at the proximate level, are influenced by circulating
androgens. Because intrasexual selection in mammals is more intense among males,
they typically dominate females. Female social dominance is therefore unexpected
and, indeed, rare. Ring-tailed lemurs (Lemur catta) are sexually monomorphic
primates in which all adult females dominate all males. The goal of our study was
to test the prediction that female dominance in this species is associated with
high androgen levels. Using two captive groups, we collected data on agonistic
behaviour and non-invasively assessed their androgen concentrations in faeces and
saliva by enzyme immunoassay. We found that adult female L. catta do not have
higher androgen levels than males. However, during the mating season there was a
twofold increase in both the androgen levels and conflict rates among females.
This seasonal increase in their androgen levels was probably not due to a general
increase in ovarian hormone production because those females showing the
strongest signs of follicular development tended to have low androgen
concentrations. At the individual level neither the individual aggression rates
nor the proportion of same-sexed individuals dominated were correlated with their
androgen levels. We conclude that female dominance in ring-tailed lemurs is
neither based on physical superiority nor on high androgen levels and that it is
equally important to study male subordination and prenatal brain priming effects
for a complete understanding of this phenomenon.
PMID- 11007330
TI - Strategic allocation of ejaculates by male Adelie penguins.
AB - Sperm competition theory suggests that males should strategically allocate sperm
to those females that will bring them the best possible genetic returns. Although
males of a number of species of insects and fishes have been shown to allocate
sperm strategically, we provide, to our knowledge, the first evidence that an
avian species is also capable of allocating ejaculates. Male Adelie penguins
(Pygoscelis adeliae) are more likely to transfer sperm during extra-pair
copulations (EPCs) than during pair copulations. We investigated the question of
how males allocate ejaculates within the constraints of limited sperm
availability and found (i) that males that engaged in EPC attempts ejaculated
less often when copulating with their social partner than males that made no EPC
attempts, and (ii) that there was no difference between males that were involved
in failed EPC attempts and those that were involved in successful EPCs in the
proportion of copulations that resulted in sperm transfer. These results indicate
that males achieve strategic allocation of sperm within the constraints of
limited sperm availability by withholding ejaculates from their social partners.
PMID- 11007331
TI - Sperm competition games played by dimorphic male beetles: fertilization gains
with equal mating access.
AB - Alternative mating tactics can generate asymmetry in the sperm competition risk
between males within species. Theory predicts that adaptations to sperm
competition should arise in males facing the greater risk. This prediction is met
in the dung beetle Onthophagus binodis where minor males which sneak copulations
have a greater expenditure on the ejaculate. In its congener Onthophagus taurus
there is a reduced asymmetry in sperm competition risk such that both tactics
have equal ejaculate expenditure. We used the irradiated male technique to test
whether adaptations to sperm competition in minor males result in higher
paternity. We found that for both species, on average, each of two males gained
equal numbers of fertilizations, confirming the assumption that sperm compete in
a raffle. There were no differences in the sperm competition success of major and
minor males in O. taurus as predicted from their equal expenditure on their
ejaculate. Contrary to expectations, there were also no differences in
fertilization success between the male tactics in O. binodis. Thus, in O. binodis
minor males must expend more on their ejaculate in order to obtain the same
fertilization gains as major males.
PMID- 11007332
TI - Sexually transmitted diseases in polygynous mating systems: prevalence and impact
on reproductive success.
AB - Studies of disease in relation to animal mating systems have focused on sexual
selection and the evolution of sexual reproduction. Relatively little work has
examined other aspects of ecological and evolutionary relationships between host
social and sexual behaviour, and dynamics and prevalence of infectious diseases;
this is particularly evident with respect to sexually transmitted diseases
(STDs). Here, we use a simulation approach to investigate rates of STD spread in
host mating systems ranging from permanent monogamy to serial polygyny or
polyandry and complete promiscuity. The model assumes that one sex (female) is
differentially attracted to the other, such that groups of varying size are
formed within which mating and disease transmission occur. The results show that
equilibrium disease levels are generally higher in females than males and are a
function of variance in male mating success and the likelihood of a female
switching groups between mating seasons. Moreover, initial rates of disease
spread (determining whether an STD establishes in a population) depend on
patterns of host movement between groups, variance in male mating success and
host life history (e.g. mortality rates). Male reproductive success can be
reduced substantially by a sterilizing STD and this reduction is greater in males
that are more 'attractive' to females. In contrast, females that associate with
more attractive males have lower absolute fitness than females associating with
less attractive males. Thus, the potential for STDs to act as a constraint on
directional selection processes leading to polygyny (or polyandry) is likely to
depend on the details of mate choice and group dynamics.
PMID- 11007333
TI - Egg maturation, egg resorption and the costliness of transient egg limitation in
insects.
AB - Although there is widespread agreement that the cost of oviposition underlies
selective oviposition in insects, there is no consensus regarding which factors
mediate the cost of oviposition. Models have suggested that egg costs are often
paramount in those insects that do not continue to mature eggs during the adult
stage (pro-ovigenic insects). Here we address the hypothesis that egg costs are
generally less significant in synovigenic insects, which can replenish oocyte
supplies through continuous egg maturation. A dynamic optimization model based on
the biology of a highly synovigenic parasitoid, Aphytis aonidiae, suggests that
the maximum rate of egg maturation is insufficient to balance the depletion of
eggs when opportunities to oviposit are abundant. Transient egg limitation
therefore occurs, which imposes opportunity costs on reproducing females. Thus,
whereas the most fundamental constraint acting on the lifetime reproductive
success of pro-ovigenic species is the fixed total number of eggs that they carry
at eclosion, the most fundamental constraint acting on a synovigenic species is
the maximum rate of oocyte maturation. Furthermore, the ability of synovigenic
species to reverse the flow of nutrients from the soma to oocytes (i.e. egg
resorption) has a dramatic influence on the cost of oviposition. Whereas females
in hostrich environments may experience oviposition-mediated egg limitation,
females in host-poor environments may experience oosorption-mediated egg
limitation. Both forms of egg limitation are costly. Contrary to initial
expectations, the flexibility of resource allocation that typifies synovigenic
reproduction actually appears to broaden the range of conditions under which
costly egg limitation occurs. Egg costs appear to be fundamental in mediating the
trade-off between current and future reproduction, and therefore are an important
factor favouring selective insect oviposition.
PMID- 11007334
TI - A modelling approach to vaccination and contraception programmes for rabies
control in fox populations.
AB - In a previous study, three of the authors designed a one-dimensional model to
simulate the propagation of rabies within a growing fox population; the influence
of various parameters on the epidemic model was studied, including oral
vaccination programmes. In this work, a two-dimensional model of a fox population
having either an exponential or a logistic growth pattern was considered. Using
numerical simulations, the efficiencies of two prophylactic methods (fox
contraception and vaccination against rabies) were assessed, used either
separately or jointly. It was concluded that far lower rates of administration
are necessary to eradicate rabies, and that the undesirable side-effects of each
programme disappear, when both are used together.
PMID- 11007335
TI - Host specificity in avian blood parasites: a study of Plasmodium and Haemoproteus
mitochondrial DNA amplified from birds.
AB - A fragment of the mitochondrial cytochrome b gene of avian malaria (genera
Haemoproteus and Plasmodium) was amplified from blood samples of 12 species of
passerine birds from the genera Acrocephalus, Phylloscopus and Parus. By
sequencing 478 nucleotides of the obtained fragments, we found 17 different
mitochondrial haplotypes of Haemoproteus or Plasmodium among the 12 bird species
investigated. Only one out of the 17 haplotypes was found in more than one host
species, this exception being a haplotype detected in both blue tits (Parus
caeruleus) and great tits (Parus major). The phylogenetic tree which was
constructed grouped the sequences into two clades, most probably representing
Haemoproteus and Plasmodium, respectively. We found two to four different
parasite mitochondrial DNA (mtDNA) haplotypes in four bird species. The
phylogenetic tree obtained from the mtDNA of the parasites matched the
phylogenetic tree of the bird hosts poorly. For example, the two tit species and
the willow warbler (Phylloscopus trochilus) carried parasites differing by only
0.6% sequence divergence, suggesting that Haemoproteus shift both between species
within the same genus and also between species in different families. Hence, host
shifts seem to have occurred repeatedly in this parasite host system. We discuss
this in terms of the possible evolutionary consequences for these bird species.
PMID- 11007336
TI - Fatal attraction in rats infected with Toxoplasma gondii.
AB - We tested the hypothesis that the parasite Toxoplasma gondii manipulates the
behaviour of its intermediate rat host in order to increase its chance of being
predated by cats, its feline definitive host, thereby ensuring the completion of
its life cycle. Here we report that, although rats have evolved anti-predator
avoidance of areas with signs of cat presence, T. gondii's manipulation appears
to alter the rat's perception of cat predation risk, in some cases turning their
innate aversion into an imprudent attraction. The selectivity of such behavioural
changes suggests that this ubiquitous parasite subtly alters the brain of its
intermediate host to enhance predation rate whilst leaving other behavioural
categories and general health intact. This is in contrast to the gross
impediments frequently characteristic of many other host parasite systems. We
discuss our results in terms of their potential implications both for the
epidemiology of toxoplasmosis and the neurological basis of anxiety and cognitive
processes in humans and other mammals.
PMID- 11007337
TI - Solvent related chronic encephalopathy.
PMID- 11007338
TI - Criteria for solvent-induced chronic toxic encephalopathy: a systematic review.
AB - In 1985, a WHO Working Group presented diagnostic criteria and a classification
for solvent-induced chronic toxic encephalopathy (CTE). In the same year, the
"Workshop on neurobehavioral effects of solvents" in Raleigh, N.C., USA
introduced a somewhat different classification for CTE. The objective of this
review is to study the diagnostic procedures that are used to establish the
diagnosis of CTE, and the extent to which the diagnostic criteria and
classification of the WHO, and the classification of the Raleigh Working Group,
are applied. A systematic search of studies on CTE was performed, and the
diagnostic criteria and use of the WHO and Raleigh classifications were listed.
We retrieved 30 original articles published in English from 1985 to 1998, in
which CTE was diagnosed. Only two articles did not report the duration of solvent
exposure. The type of solvent(s) involved was described in detail in four
articles, poorly in 17 articles, and not at all in nine articles. Tests of
general intelligence were used in 19 articles, and tests of both attention and
mental flexibility and of learning and memory were used in 18 articles.
Exclusion, by interview, of potentially confounding conditions, such as somatic
diseases with central nervous effects and psychiatric diseases, was reported in
21 and 16 articles, respectively. In only six of the articles were both the WHO
diagnostic criteria and the WHO or Raleigh classifications used. In the future,
parameters of exposure, psychological test results, and use of medication that
possibly affects psychological test results should always be described. We list
some advantages and disadvantages of the Raleigh and WHO classifications. To aid
inter-study comparisons, the diagnosis of CTE should be categorized and reported
according to an internationally accepted classification.
PMID- 11007339
TI - Exposure and acute exposure-effects before and after modification of a
contaminated humidification system in a synthetic-fibre plant.
AB - OBJECTIVE: Follow-up study of exposure and acute exposure-effects after
modification to steam humidification of a contaminated cold water system which
had caused an outbreak of humidifier fever in a synthetic-fibre plant. METHODS:
Before and after modification of the system aerobiological measurements were
performed. Concentrations of fungi and bacteria, in colony forming units (cfu)
per m3, were measured by stationary air sampling with an Andersen sampler.
Endotoxin levels (pg/m3) were determined by Limulus Amoebocyte Lysate (LAL) assay
in pooled dust from personal air sampling. An indication of exposure levels of
oil-mist was obtained by monitoring with a direct reading optical photometer.
Changes as acute exposure-effects in spirometry and white blood cell count,
during an afternoon shift were compared in exposed and non-exposed workers before
and after modification. RESULTS: Measured levels of fungi, total bacteria, Gram
negative bacteria and endotoxins both before and after modification were below
levels which would be expected to be associated with the exposure-effects.
However, after modification, we found that the statistically significant
differences in levels of bacteria and endotoxins with a department without
humidification no longer existed. Mean oil-mist concentrations were below 1
mg/m3, with short-time peak exposure during certain tasks of up to 5 mg/m3.
Before modification, in exposed workers there was significantly more decline of
spirometry, and more increase of white blood cell count during the first
afternoon shift, compared with non-exposed workers. In exposed workers, the white
blood cell count increase was positively associated with decline of spirometry.
After modification, differences between exposed and non-exposed workers no longer
existed. CONCLUSION: Follow-up investigation of acute exposure-effects
demonstrated the effectiveness of remedial actions taken against a contaminated
humidification system. Follow-up of exposure-effects in particular is recommended
when there is doubt about the interpretation of exposure measurements.
PMID- 11007340
TI - Follow-up study of workers in a nylon carpet yarn plant after remedial actions
taken against a contaminated humidification system.
AB - OBJECTIVE: To investigate the effectiveness of remedial actions taken against a
contaminated humidification system, after an outbreak of humidifier disease in a
nylon carpet yarn plant. METHODS: Two and 6 years after modification, a follow-up
investigation of a stratified (age, smoking habits) sample of exposed (n = 75)
and non-exposed (n = 56) workers was carried out. Outcome-parameters were:
respiratory symptoms, spirometry, skin tests and serology with various humidifier
fungi. In addition, the yearly incidence of work-disability because of chronic
respiratory disease during the 2 years before, and 11 years after the
modification was compared. RESULTS: At follow-up, exposed workers, who remained
at the same workplace no longer had significantly more frequent chronic
respiratory symptoms. The prevalence of positive serology was still higher (P <
0.05) in exposed workers after 2 years, but at the 6 year follow-up
investigation, the difference was no longer significant. Prevalence of positive
skin tests after 2 years no longer differed from that of the non-exposed workers.
Slopes (ml/years) of the graphs of forced vital capacity (FVC) and one-second
forced expiratory volume (FEV1) during the 6 year follow-up after the first
investigation did not differ between exposed and non-exposed workers, both before
and after adjustment for age, smoking habits and results of skin tests and
serology before modification. Before modification, exposed workers with a
positive late skin test had a lower FVC than non-exposed workers. After 6 years
of follow-up their FVC was still lower, but the difference was no longer
significant. There were no indications of selective loss to follow-up. After
remedial actions no new cases of humidifier disease occurred. Moreover, the
yearly incidence of work-disability in this plant because of chronic respiratory
disease, decreased from 1.30% to 0.27% compared with a decrease from 0.30% to 0.
12% in other synthetic fibre plants. CONCLUSION: Follow-up investigation of
exposure-effects demonstrated the effectiveness of remedial actions taken against
a contaminated humidification system.
PMID- 11007341
TI - Homozygous gene deletions of the glutathione S-transferases M1 and T1 are
associated with thimerosal sensitization.
AB - OBJECTIVE: Thimerosal is an important preservative in vaccines and ophthalmologic
preparations. The substance is known to be a type IV sensitizing agent. High
sensitization rates were observed in contact-allergic patients and in health care
workers who had been exposed to thimerosal-preserved vaccines. There is evidence
for the involvement of the glutathione system in the metabolism of thimerosal or
its decomposition products (organomercury alkyl compounds). Thus detoxification
by polymorphically expressed glutathione S-transferases such as GSTT1 and GSTM1
might have a protective effect against sensitization by these substances.
METHODS: To address this question, a case control study was conducted, including
91 Central European individuals with a positive patch-test reaction to
thimerosal. This population was compared with 169 healthy controls and
additionally with 114 individuals affected by an allergy against para-substituted
aryl compounds. The latter population was included in order to test whether
possible associations were due to substance-specific effects, or were a general
feature connected with type IV immunological diseases. Homozygous deletions of
GSTT1 and GSTM1 were determined by polymerase chain reaction. RESULTS:
Glutathione S-transferase M1 deficiency was significantly more frequent among
patients sensitized to thimerosal (65.9%, P = 0.013) compared with the healthy
control group (49.1%) and the "para-compound" group (48%, P = 0.034). Glutathione
S-transferase T1 deficiency in the thimerosal/mercury group (19.8%) was barely
elevated versus healthy controls (16.0%) and the "para-compound" group (14.0%).
The combined deletion (GSTT1-/GSTM1-) was markedly more frequent among thimerosal
sensitized patients than in healthy controls (17.6% vs. 6.5%, P = 0.0093) and in
the "para-compound" group (17.6% vs. 6.1%, P =0.014), revealing a synergistic
effect of these enzyme deficiencies (healthy controls vs. thimerosal GSTM1
negative individuals, OR = 2.0 [CI = 1.2-3.4], GSTT1-, OR = 1.2 [CI = 0.70-2.1],
GSTM1/T1-, OR = 3.1 [CI = 1.4-6.5]). CONCLUSIONS: Since the glutathione-dependent
system was repeatedly shown to be involved in the metabolism of thimerosal
decomposition products, the observed association may be of functional relevance.
PMID- 11007342
TI - Comparison between blood and urinary toluene as biomarkers of exposure to
toluene.
AB - OBJECTIVES: To compare blood toluene (TOL-B) and urinary toluene (TOL-U) as
biomarkers of occupational exposure to toluene, and to set a suitable procedure
for collection and handling of specimens. METHOD: An assay based on headspace
solid-phase microextraction (SPME) was used both for the determination of toluene
urine/air partition coefficient (lambdaurine/air) and for the biological
monitoring of exposure to toluene in 31 workers (group A) and in 116 non
occupationally exposed subjects (group B). Environmental toluene (TOL-A) was
sampled during the work shift (group A) or during the 24 h before specimen
collection (group B). Blood and urine specimens were collected at the end of the
shift (group A) or in the morning (group B) and toluene was measured. RESULTS:
Toluene lambdaurine/air was 3.3 +/- 0.9. Based on the specimen/air partition
coefficient, it was calculated that the vial in which the sample is collected had
to be filled up to 85% of its volume with urine and 50% with blood in order to
limit the loss of toluene in the air above the specimen to less than 5%.
Environmental and biological monitoring of workers showed that the median
personal exposure to toluene (TOL-A) during the work-shift was 80 mg/m3, the
corresponding TOL-B was 82 microg/l and TOL-U was 13 microg/l. Personal exposure
to toluene in environmentally exposed subjects was 0.05 mg/m3, TOL-B was 0.36
microg/l and TOL-U was 0.20 microg/l. A significant correlation (P < 0.05) was
observed between TOL-B or TOL-U and TOL-A (Pearson's r = 0.782 and 0.754) in
workers, but not in controls. A significant correlation was found between TOL-U
and TOL-B both in workers and in controls (r = 0.845 and 0.681). CONCLUSION: The
comparative evaluation of TOL-B and TOL-U showed that they can be considered to
be equivalent biomarkers as regards their capacity to distinguish workers and
controls and to correlate with exposure. However, considering that TOL-U does not
require an invasive specimen collection, it appears to be a more convenient tool
for the biological monitoring of exposure to toluene.
PMID- 11007343
TI - Study of some immunological parameters in workers occupationally exposed to
benzene.
AB - OBJECTIVE: The aim of the study was to investigate the immunotoxicity of benzene
exposure, to establish the correlation between the exposure biomarkers and some
immunological parameters, and to assess the possible influence of confounding
factors on the results of immunological assay applicable in routine medical
surveillance of benzene-exposed workers. METHODS: Forty-nine female workers in
the shoemaking industry who were exposed to solvent mixtures and 27 nonexposed
controls were examined. Workers were exposed to benzene concentrations of up to
15 ppm, and to toluene of up to 50 ppm. RESULTS: Significant differences in the
levels of benzene and toluene in blood and phenols in post-shift urine between
the exposed and the control group confirmed solvent exposure. The number of B
lymphocytes (P = 0.01) was lower in the shoe workers than in the controls.
Significant correlation was found between the level of immunoglobulin G and
benzene in the work atmosphere, while confounding factors had no impact on
immunological values. CONCLUSION: According to these results, exposure to benzene
concentration lower than 15 ppm can induce depression of the circulating B
lymphocyte level and therefore this fact could be used to develop a promising
method for health surveillance of benzene-exposed workers. However, considerably
more effort in the research on benzene immunotoxicity, especially in the search
for suitable health surveillance methods, is still required.
PMID- 11007344
TI - Experimental exposure to methylformate and its neurobehavioral effects.
AB - OBJECTIVES: The aim of the study was to investigate the acute effects of
experimental methylformate exposure on the nervous system. METHODS: In an
exposure chamber, 20 subjects were exposed to methylformate at 100 ppm [Swiss
maximum allowable concentration (MAC)] for 8 h. The same number of subjects with
the same ages (between 20 and 30 years), gender and education level (university)
were examined by the same procedure as a control group. The subjects did not know
if they were exposed or not. Three times (morning, noon, evening) during these 8
h, mood [Profile of Mood States (POMS)], neurobehavioral performance (reaction,
Stroop, nonverbal learning, determination, tracking; Wiener Test System), vision
(visual acuity, contrast sensitivity, color sensitivity) and postural sway were
tested. During an undemanding test (POMS) and a demanding performance task
(determination test), pulse, electromyography (EMG) of the forehead and of the
neck were recorded. In the morning and evening spirometry [forced vital capacity
(FVC), forced one-second expiration volume (FEV), medium expiration flow (MEF)
and peak expiration flow (PEF)] and the odor perception threshold were measured.
RESULTS: In the evening, in the exposed group, fatigue was significantly
increased and the EMG of the forehead during a demanding task showed a different
development during exposure. The other tests showed no significant solvent
effect, but 16 of 43 test parameters showed a significant effect of time.
CONCLUSIONS: The results of this study indicate a possible effect of
methylformate exposure on the subjective feeling of fatigue after 8 h exposure at
100 ppm in young and healthy subjects, without measurable impairment of
neurobehavioral performance. We assume that a similar effect in normal work,
combined with a heavy workload and shift work, can lead to an impairment of
productivity, and increase the risk of accidents.
PMID- 11007345
TI - Urinary methanol and formic acid as indicators of occupational exposure to methyl
formate.
AB - OBJECTIVE: To evaluate the validity of methanol (MeOH) and formic acid (FA) in
urine as biological indicators of methyl formate (MF) exposure in experimental
and field situations. METHODS: The subjects were 28 foundrymen and two groups of
volunteers (20 control and 20 exposed). Exposure assessment of the workers was
performed by personal air and biological monitoring. Methyl formate vapour
collected on charcoal tube was analysed by gas chromatography. The concentration
of MF in the exposure chamber (volunteer-study) was monitored by two independent
methods [flame ionisation detection (FID) and Fourier transformation infra-red
detection (FTIR)]. Urinary metabolites (MeOH and FA) were analysed separately by
headspace gas chromatography. RESULTS: The volunteers exposed to 100 ppm MF
vapour at rest for 8 h excreted 3.62 +/- 1.13 mg MeOH/l (mean +/- SD) at the end
of the exposure. This was statistically different (P < 0.001) from pre-exposure
MeOH excretion (2.15 +/- 0.80 mg/1), or from that of controls (1.69 +/- 0.48
mg/l). The urinary FA excretion was 32.2 +/- 11.3 mg/g creatinine after the
exposure, which was statistically different (P < 0.001) from pre-exposure
excretion (18.0 +/- 9.3 mg/g creatinine) or that of controls (13.8 +/- 7.9 mg/g
creatinine). In foundrymen, the urinary FA excretion after the 8 h workshift
exposure to a time weighted average (TWA) concentration of 2 to 156 ppm MF showed
a dose-dependent increase best modelled by a polynomial function. The highest
urinary FA concentration was 129 mg/g creatinine. The pre-shift urinary FA of the
foundrymen (18.3 +/- 5.6 mg/g creatinine) did not differ from that of controls
(13.8 +/- 7.9 mg/g creatinine). The urinary MeOH excretion of the foundrymen
after the shift, varied from < 1 to 15.4 mg/l, while the correlation with the
preceding MF exposure was poor. The foundrymen excreted more (P = 0.01) FA (2.12
+/- 3.56 mg/g creatinine) after the workshift than experimentally, once-exposed
volunteers (0.32 +/- 0.11 mg/g creatinine) at a similar inhaled MF level of 1
ppm). CONCLUSIONS: In spite of its high background level in non-exposed subjects,
urinary FA seems to be a useful biomarker of methyl formate exposure. The
question remains as to what is the reason for the differences in chronic and
acute exposure respectively.
PMID- 11007346
TI - Skin absorption of some vaporous solvents in volunteers.
AB - OBJECTIVES: To determine the dermal absorption rates of vaporous 1,1,1
trichloroethane (111TRI), trichloroethene (TRI), tetrachloroethene (TETRA),
hexane (HEX), toluene (TOL) and m-xylene (XYL) in humans. The determined
absorption data were used for the validation of two published models for
prediction of non-steady-state skin absorption. METHODS: Five volunteers were
dermally exposed on an area of about 1,000 cm2 (forearm and hand) for 20 or 30
min. An inhalation exposure with a known dose rate served as a reference. Using
the solvent concentrations in exhaled air, measured after both inhalation and
dermal exposure, we calculated the maximum absorption rate into the blood, and
the average absorption rates into the skin throughout the exposure, using the
linear system dynamics method. RESULTS: The absorption rates into the skin,
normalised for exposure concentration, amounted to 0.021 cm/h (111TRI), 0.049
cm/h (TRI), 0.054 cm/h (TETRA), 0.013 cm/h (HEX), 0.14 cm/h (TOL), and 0.12 cm/h
(XYL). The maximum absorption rates into the blood ranged from 0.005 nmol/h for
111TRI and HEX to 0.050 nmol/hr for TOL. The ratios between the predicted and
experimental values of the absorption rates into the skin ranged, for the model
of Cleek and Bunge [4], from 0.3 (HEX) to 1.1 (TRI and TETRA), and for the model
of Wilschut and Ten Berge [22], from 1.1 (HEX) to 4.7 (XYL). CONCLUSION: The
linear system dynamics method allowed us to calculate not only the total amount
absorbed by the skin but also the maximum absorption rate into the blood. The
steady-state absorption rate, usually described by a permeability constant, will
be below the absorption rate into the skin and above the maximum absorption rate
into the blood. The skin absorption rates predicted by the models showed a good
agreement with the experimental values. A comparison of the estimated whole-body
skin uptake with the inhalatory uptake from the same atmosphere, revealed that
the dermal uptake contributed from 0.1% (HEX) to 1% (TOL and XYL) to the total
uptake.
PMID- 11007347
TI - Quaternary ammonium compounds and occupational asthma.
AB - OBJECTIVE: Quaternary ammonium compounds, among which benzalkonium chloride is
one of the best-known, are commonly used as antiseptics, disinfectants,
detergents and preservatives. They can cause occupational asthma, which however,
has been rarely reported so far, despite wide use of these products. We report
three such cases. Possible mechanisms causing asthma are discussed, taking into
account their characteristics. METHODS AND RESULTS: Our patients, all female
nurses, manifested asthma symptoms upon handling disinfectant solutions
containing benzalkonium chloride. Work-related fall in PEFR was observed in all
of them. The diagnosis was confirmed by challenge tests where the patients were
exposed, in a closed chamber, to suspected disinfectant contained in a tray. All
of the women developed early or delayed symptoms upon exposure. Similar challenge
tests to placebo or other disinfectants devoid of quaternary ammonium compound
were negative. CONCLUSION: These three cases, in addition to others reported in
the literature, point out an as yet poorly known etiology of occupational asthma
to quaternary ammonium compounds in hospital employees. The exact mechanism of
the action remains unexplained.
PMID- 11007349
TI - Web alert. Transplantation cancer.
PMID- 11007348
TI - Recommendations for the categorization of germ cell mutagens.
AB - Germ cell mutagens are currently classified into three categories in the German
List of MAK and BAT Values. These categories have been revised and extended by
analogy with the new categories for carcinogenic chemicals. Germ cell mutagens
produce heritable gene mutations, and heritable structural and numerical
chromosome aberrations in germ cells. The original categories 1 and 2 for germ
cell mutagens remain unchanged. Two new categories 3A and 3B are proposed for
chemicals suspected to be germ cell mutagens. A new category 5 is proposed for
germ cell mutagens with low potency that contribute negligibly to human genetic
risk provided the MAK value is observed.
PMID- 11007350
TI - The impact of preprint servers and electronic publishing on biomedical research.
PMID- 11007351
TI - Xenotransplantation: reappraising the risk of retroviral zoonosis.
PMID- 11007352
TI - Chemokines and their receptors in allograft rejection.
AB - Despite current recognition of over 40 chemokines and more than 18 chemokine
receptors, understanding of their role in transplant immunobiology and transplant
rejection is extremely limited and fragmentary. Recent literature has
demonstrated the presence of chemokines and their receptors in transplants and
some studies demonstrate important functional roles.
PMID- 11007353
TI - Mechanisms of chronic rejection.
AB - Chronic rejection remains the major obstacle to long-term allograft survival.
Detailed understanding of putative etiologic risk factors, both antigen-dependent
and -independent, is important for designing effective therapeutic strategies to
ameliorate this process. Cell senescence may be an important factor in chronic
rejection.
PMID- 11007354
TI - The role of T cell apoptosis in transplantation tolerance.
AB - Rejection of fully MHC-mismatched allografts entails the direct recognition of
donor MHC molecules (direct antigen presentation) and the activation of an
unusually large mass of alloreactive T cells. There is compelling evidence that
apoptotic cell death of activated T cells is a critical initial step in the
induction of peripheral allograft tolerance with regimens that are not inherently
lymphoablative and that therapies that block T cell activation and T cell
apoptosis also block the acquisition of tolerance. Thus, T cell apoptosis may
play an important role in reducing the size of cytopathic T cell clones and this
process may also promote the development and expansion of immune regulatory cells
that are essential in the maintenance of allograft tolerance.
PMID- 11007355
TI - Dendritic cells and prospects for transplantation tolerance.
AB - The past year has witnessed the resolution of some long-standing enigmas
surrounding the immunobiology of dendritic cells, illuminating their opposing
roles in peripheral tolerance and allograft rejection. Nevertheless these
advances have posed many new questions, the answers to which may subtly influence
our approach to the treatment of rejection while bringing ever closer the
prospect of donor-specific transplanation tolerance.
PMID- 11007356
TI - Tolerance induction by 'megadose' transplants of CD34+ stem cells: a new option
for leukemia patients without an HLA-matched donor.
AB - Early studies in murine models and more recent clinical data in heavily pre
treated leukemia patients have shown that escalation of the dose of hematopoietic
progenitor cells can overcome major genetic barriers and enable rapid and durable
engraftment of haploidentical, three-locus-mismatched transplants without graft
versus-host disease. In vitro studies suggest that veto cells within the
progenitor population most probably mediate this facilitating effect.
PMID- 11007357
TI - New strategies for bone marrow transplantation.
AB - Adoptive immunotherapy of hematologic malignancies and metastatic solid tumors by
donor lymphocyte infusion following induction of host-versus-graft
transplantation tolerance against can best be achieved following nonmyeloablative
stem-cell transplantation (NST). Induction of mixed chimerism may represent the
best approach for induction of transplantation tolerance to donor alloantigens.
Thus NST may become the optimal approach for the treatment of nonmalignant
diseases, where replacement of host with donor hematopoietic cells is indicated:
for correction of genetic or stem cell deficiency diseases; as a platform for
immunotherapy of autoimmune or infectious diseases; or for induction of tolerance
to organ allografts.
PMID- 11007358
TI - Knowledge about transplantation tolerance gained in primates.
AB - Research in transplantation tolerance relies on application of successful
strategies in a nonhuman-primate organ transplant model for preclinical testing.
Three principal approaches are being evaluated: hematopoietic chimerism,
lymphocyte depletion and costimulation blockade. Interactive work in these three
areas has yielded much new information on mechanisms of tolerance and opened the
door to pilot clinical trials. Clinical application of xenotransplantation is
likely to depend on such strategies.
PMID- 11007359
TI - Pharmacodynamics of immunosuppressive drugs.
AB - The inability to measure the effects of immunosuppressive drugs on immune cells
in vivo has always severely limited preclinical drug development, the design and
interpretation of clinical trials and the optimal clinical use of this drug class
in transplantation. Now, new technologies using microliter samples of whole blood
and exploiting the specificity, sensitivity and versatility of flow cytometry
have been developed. These novel techniques not only are illuminating the 'black
box' that has obscured the pharmacodynamic effects of immunosuppressants but also
are uncovering new mechanisms of action of these drugs. Pharmacodynamic assays
measure biologically relevant events in vivo, since changes in lymphocyte
functions in blood collected from immunosuppressed graft recipients faithfully
reflect histopathologic events within allograft tissue.
PMID- 11007360
TI - Prospects for xenotransplantation.
AB - Pig-to-primate organ survival has been extended from a few minutes to weeks and
occasionally months, following the development of transgenic pigs that express
human complement-regulatory proteins, efficient antibody removal technologies and
immunosuppressive strategies. The current limitation to the clinical application
of this technology is acute vascular rejection, and an understanding of the
mechanisms of this process and the development of modalities to overcome it are
key to making significant progress at solving the critical shortage of organs for
transplantation. Approaches that address this issue are underway in a number of
laboratories.
PMID- 11007361
TI - Cytokine-secreting tumor cell vaccines.
AB - Modification of the tumor microenvironment with gene transfer techniques
stimulates two immune mechanisms that effectuate tumor destruction. One involves
improved tumor-antigen presentation for the development of specific cellular and
humoral immunity. The second involves compromise of the tumor vasculature by
soluble factors and leukocytes.
PMID- 11007362
TI - Design and evaluation of antigen-specific vaccination strategies against cancer.
AB - After studies in preclinical mouse models, the efficacy and safety of tumor
specific vaccination strategies is currently being evaluated in cancer patients.
The first wave of clinical trials has shown that in general such vaccination
strategies are safe. However examples of clinical responses, especially in
conjunction with vaccine-induced immune responses, are still scarce. The fact
that most trials have so far been performed with end-stage cancer patients can
largely account for this deficit. Greater efficacy of anticancer vaccines is
expected in patients with less-progressed disease. In addition, the detection of
both natural and vaccine-induced T cell immunity needs further improvement.
PMID- 11007363
TI - The dendritic cell and human cancer vaccines.
AB - Over the past ten years, the identification of the critical role that dendritic
cells (DCs) play in stimulating a specific immune response has led to their use
in cancer and HIV therapy. Interesting responses have been reported but the most
effective approach and the duration of these responses are still unclear. The
quality of DCs, the means by which tumor antigens are delivered to DCs and the
problems associated with monitoring the immune response have made individual
studies difficult to compare. Much work is still needed to determine the role
that DC-based cancer vaccines will have, the most effective way to deliver DCs to
patients and the most relevant antigens to provide to DCs.
PMID- 11007364
TI - Costimulatory wars: the tumor menace.
AB - Advances in our understanding of T cell costimulatory molecules have provided a
vast array of novel approaches to tumor immunotherapy. In the past year,
combinatorial immunotherapy based on earlier studies of CTLA-4 blockade, the
identification of novel B7-family members, the modulation of CD40 to reverse
tolerance to tumor-associated antigens and the use of OX40 to enhance antitumor
responses of CD4+ T cells have all contributed to the development of more
powerful immunomodulatory cancer therapies.
PMID- 11007366
TI - The role of peritoneal dialysis as the first-line renal replacement modality.
AB - Twenty years after its introduction, peritoneal dialysis (PD) is a well
established alternative to hemodialysis (HD) as a modality of renal replacement
therapy. Much debate and research is apparent in the literature, comparing
hemodialysis and PD as "opposite" modalities and trying to ascertain which
modality should be more optimal. In our opinion, HD and PD are two distinct
modalities, each with its own advantages and disadvantages. In addition, it is
clear that for both HD and PD, rates of technique failure are high, causing
patients to transfer between modalities. The question is thus not which modality
is best, but rather, which flow-chart of modalities makes best use of the
advantages of each modality, while avoiding its disadvantages. In this respect,
HD and PD appear to be complementary modalities. The better preservation of
residual renal function, lower risk of infection with hepatitis B and C, better
outcome after transplantation, preservation of vascular access, and lower costs
are arguments to promote PD as a good initial treatment. When PD-related problems
arise (adequacy, ultrafiltration, peritonitis, patient burnout), a timely
transfer to HD has to be planned. This editorial tries to review arguments
supporting the complementary nature of both modalities, and especially the role
of PD as the first-line renal replacement therapy.
PMID- 11007365
TI - Building better vaccines: how apoptotic cell death can induce inflammation and
activate innate and adaptive immunity.
AB - The immunological consequences of apoptosis have been hotly debated. Apoptosis
was originally described as a set of cellular morphological changes that occur in
the absence of inflammation but the term has been redefined on the basis of a set
of conserved molecular events that include the activation of caspases. Though the
apoptosis occurring during normal development is immunologically bland or even
tolerizing, the apoptotic death after viral infection or after the ligation of
Fas can trigger powerful innate and adaptive immune responses. The molecular
machinery at the nexus of apoptosis and inflammation includes caspase-1 --an
activator of IL-1beta and IL-18 - as well as the double-stranded-RNA-dependent
protein kinase pathway and RNaseL pathway, which are key effectors of antiviral
immunity. New proapoptotic vaccines induce immune responses that may be able to
prevent or treat infectious disease and cancer.
PMID- 11007367
TI - Treatment of peritonitis: update or new course.
PMID- 11007368
TI - Early start to peritoneal dialysis: to start or not to start?
PMID- 11007369
TI - Sclerosing encapsulating peritonitis: what approach should be taken with
children?
PMID- 11007370
TI - Preservation of residual renal function--an important goal.
PMID- 11007371
TI - Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000
update.
PMID- 11007372
TI - Preliminary evaluation of incremental peritoneal dialysis in 25 patients.
AB - BACKGROUND: Incremental dialysis has been suggested for patients with some
residual renal function. However, very little published clinical data exist on
the feasibility of this schedule. OBJECTIVES: To assess feasibility of
incremental dialysis, with regard to its effect, complications, and impact on
quality of life. DESIGN: Pilot prospective study, not controlled. SETTING:
Nephrology division, public clinical research hospital. PATIENTS: Twenty-five
patients (19 men, mean age 61+/-13 years, body weight 63+/-11 kg) began
peritoneal dialysis (the first treatment of uremia) with a single nightly
exchange lasting 10 hours or 2 daily exchanges over 12 hours according to
creatinine clearance and Kt/N. Patients gave informed consent and reported their
work activity, degree of rehabilitation, and their quality of life by answering a
questionnaire prepared for this purpose. OUTCOME MEASURES: Survival rate,
complications related to peritoneal dialysis, and residual renal and peritoneal
clearances. RESULTS: During the study period no patient died. Complications
related to dialysis were peritonitis (0.41 episodes/year) and exit-site infection
(0.32 episodes/year). All patients continued to work with full rehabilitation and
considered 1 or 2 exchanges per day less troublesome than 3 or 4. CONCLUSIONS:
Incremental dialysis is well accepted by patients and staff. This technique does
not involve a high risk of complications and is economical. Therefore incremental
dialysis is feasible.
PMID- 11007373
TI - Incremental initiation of dialysis: one center's experience over a two-year
period.
AB - OBJECTIVE: This pilot study describes our center's experience with peritoneal
dialysis (PD) over the past 2 years using a "healthy start" dialysis protocol
with an incremental approach to prescription management. DESIGN: Nonrandomized,
prospective pilot study. SETTING: Single PD unit of a university teaching
hospital. PATIENTS: Thirteen PD patients who initiated dialysis at our center
from April 1997 to June 1999. METHODS: Patients initiating PD with residual renal
Kt/V of 1.0 - 2.0/week were invited to participate. They were given an initial
dialysis prescription so that total (residual renal + dialysis) weekly Kt/V
exceeded 2.0. The dialysis prescription was "incrementally" increased as residual
renal function (RRF) declined. Data collected for all patients included monthly
serum chemistries, residual renal weekly Kt/V and creatinine clearance (CCr) at 1
to 2-month intervals, and peritoneal weekly Kt/V and CCr at 3-month intervals
and 1 month after each prescription change. RESULTS: To date, we have followed 13
patients on our incremental PD protocol for a total of 159.3 patient-months. Mean
serum albumin concentration and mean normalized protein equivalent of nitrogen
appearance (nPNA) were stable throughout the study. Mean total Kt/V and CCr
remained above the recommended targets of 2.0/wk and 60 L/wk, respectively.
Residual renal function declined rather slowly in our PD patients. One patient
died from complications of aortic valve surgery and a second died from pneumonia.
A third patient died from peritonitis. One patient required a new Tenckhoff
catheter after catheter migration. Three patients were temporarily switched to
hemodialysis after a hernia repair, a pleural leak, and elective
native/transplant nephrectomies, respectively. Two patients were permanently
switched to hemodialysis: one after an episode of peritonitis, the second after
accidentally damaging his PD catheter. CONCLUSIONS: Providing incremental
dialysis to maintain adequate total small solute clearance has been technically
feasible in our patient population. However, a larger than expected number of
complications was seen in our study. Fortunately, complications were easier to
manage due to the presence of RRF. Because this study was not designed to compare
outcome with that observed after traditional initiation of dialysis, further
large-scale studies are needed.
PMID- 11007374
TI - Continuous adaptation of the dialysis prescription maintains adequate Kprt/V in
CAPD patients.
AB - OBJECTIVE: To analyze the effect of individual adaptation of the dialysis
prescription in continuous ambulatory peritoneal dialysis (CAPD), as compensation
for the decline of residual renal function (RRF), on peritoneal (Kpt/V) and total
(Kprt/V) urea clearance as well as on peritoneal (Kpcr) and total weekly
creatinine clearances (CCr). DESIGN: Retrospective analysis of a 2-year period.
PATIENTS: We analyzed 18 patients [15 male, 3 female; mean age 58.2 (24 - 80)
years]. MAIN OUTCOME MEASURES: Correlations between increased dialysis
prescription and Kpt/V, Kprt/V, and Kpcr. Kprt/V and CCr measurements were based
on a 24-hour dialysate and urine collection. Measurements were performed over a
time period of 3 to 6 months. RESULTS: The results show a linear correlation
between Kpt/V and Kpcr and the prescribed volume by kilogram body weight. Kprt/V
was increased slightly by increasing the dialysis prescription. Dialysate-to
plasma (D/P) ratios of urea and creatinine remained unchanged. The mean
prescribed dialysate volume increased from 7.4+/-1.1 L to 10.6+/-2.5 L. Mean
Kprt/V could be maintained on a stable level for a 36-month period. CONCLUSION:
By adapting the dialysis prescription on an individual basis to the continuous
decline of RRF, and taking the patient's body weight into account in the
prescription decision, the increases in Kpt/V offset the decline in RRF. We
recommend early individualization of prescription for patients on CAPD.
PMID- 11007375
TI - Rate of decline of residual renal function in patients on continuous peritoneal
dialysis and factors affecting it.
AB - OBJECTIVE: We analyzed residual renal function (RRF) in a large number of new
peritoneal dialysis (PD) patients to prospectively define the time course of
decline of RRF and to evaluate the risk factors assumed to be associated with
faster decline. STUDY DESIGN: Single-center, prospective cohort study. SETTING:
Home PD unit of a tertiary care University Hospital. PATIENTS: The study included
242 patients starting continuous PD between January 1994 and December 1997, with
a minimum follow-up of 6 months and at least three measurements of RRF.
MEASUREMENT: All patients had data on demographic and laboratory variables,
episodes of peritonitis and the use of aminoglycoside (AG) antibiotics, temporary
hemodialysis, and number of radiocontrast studies. Adequacy of PD was measured
from 24-hour urine and dialysate collection and peritoneal equilibration test
using standard methodology. Further data on RRF was collected every 3 to 4 months
until the patient became anuric (urine volume < 100 mL/day or creatinine
clearance < 1.0 mL/min) or until the end of study in December 1998. OUTCOME
MEASURE: The slope of the decline of residual glomerular filtration rate (GFR)
(an average of renal urea and creatinine clearance) was the main outcome measure.
Risk factors associated with faster decline were evaluated by a comparative
analysis between patients in the highest and the lowest quartiles of the slopes
of GFR, and a multivariate analysis using a stepwise option within linear
regression and general linear models. RESULTS: There was a gradual deterioration
of residual GFR with time on PD, with 40% of patients developing anuria at a mean
of 20 months after the initiation of PD. On multivariate analysis, use of a
larger volume of dialysate (p = 0.0001), higher rate of peritonitis (p = 0.0005),
higher use of AG (p = 0.0006), presence of diabetes mellitus (p = 0.005), larger
body mass index (BMI) (p = 0.01), and no use of antihypertensive medications (p =
0.04) independently predicted the steep slope of residual GFR. Male gender,
higher grades of left ventricular dysfunction, and higher 24-hour proteinuria
were associated with faster decline on univariate analysis only. CONCLUSION:
Faster decline of residual GFR corresponds with male gender, large BMI, presence
of diabetes mellitus, higher grades of congestive heart failure, and higher 24
hour proteinuria. Higher rate of peritonitis and use of AG for the treatment of
peritonitis is also associated independently with faster decline of residual GFR.
Whether the type of PD (CAPD vs CCPD/NIPD) is associated with faster decline of
residual GFR remains speculative.
PMID- 11007376
TI - Residual renal function in a large cohort of peritoneal dialysis patients: change
over time, impact on mortality and nutrition.
AB - OBJECTIVE: Residual renal function contributes importantly to total solute
clearance in peritoneal dialysis (PD) patients. This study was designed to
examine the progression of residual renal function over time and its impact on
nutrition and mortality in PD patients in the six New England states (ME, NH, VT,
CT, MA, RI) comprising End Stage Renal Disease (ESRD) Network 1. DESIGN: As part
of the ESRD Clinical Indicators Project, data on 990 PD patients in Network 1
were abstracted from data supplied by dialysis units in the fourth quarter of
1997. This included demographic information; dose of PD in L/day; weekly renal,
dialysis, and total Kt/V urea; weekly renal, dialysis, and total creatinine
clearance (CCr); serum albumin level; and mortality and transplantation
information. Data collection was repeated in the second and fourth quarters of
1998 and in the second quarter of 1999. PATIENTS: 990 PD patients in Network 1.
OUTCOME MEASURES: The change in total and renal solute clearances over time, the
relationship between renal clearance and mortality, and the relationship between
renal clearance and nutritional status, as represented by serum albumin. RESULTS:
Over the 2-year period, mean weekly renal Kt/V urea and weekly renal CCr dropped
significantly. To examine the effect of residual renal function on mortality,
patients were divided into high and low (above and below the median) weekly renal
Kt/V urea and weekly renal CCr groups. Patients above the median levels of both
weekly renal Kt/V urea and weekly renal CCr had a significantly decreased risk of
dying during the observation period, after controlling for age, gender, serum
albumin level, and diabetic status [OR for high vs low renal Kt/V urea 0.54 (CI
0.34 - 0.84), OR for high vs low renal CCr 0.61 (CI 0.40 - 0.94)]. The mean
weekly renal Kt/V urea was significantly and directly correlated with the mean
serum albumin level by Spearman rank correlation (R = 0.133, p < 0.001), as was
the mean weekly renal CCr (R = 0.115, p < 0.001). CONCLUSIONS: Residual renal
function is an important contributor to total solute clearance in PD patients.
Even at low levels it is linked to decreased mortality and better nutritional
status.
PMID- 11007377
TI - Long-term peritoneal dialysis is a risk factor of sclerosing encapsulating
peritonitis for children.
AB - OBJECTIVE: Sclerosing encapsulating peritonitis (SEP) is a clinical syndrome with
a high mortality rate and is a serious complication of peritoneal dialysis (PD).
Peritoneal sclerosis (PS) is a histological diagnosis. PS is usually observed in
the peritoneal specimens of patients with SEP. Avoiding SEP is considered to be
extremely important for pediatric patients who may require long-term PD. In this
study, the characteristics of patients with PS were investigated to determine
when to perform peritoneal biopsies and how long PD can be performed safely.
DESIGN: A retrospective single-center study. SETTING: Tokyo Metropolitan Kiyose
Children's Hospital. PATIENTS: A total of 109 children younger than 16 years have
received chronic PD in our unit since 1981. Among these children, 16 patients had
been on PD for more than 5 years (mean 7.4+/-2.5 years) from May 1992 to March
1999. Peritoneal biopsies were performed in 14 of the 16 patients, who were
divided into two groups based on the histological diagnoses: a PS and a
peritoneal fibrosis (PF) group. RESULTS: The 14 patients were on PD for a mean of
7.8+/-2.5 years. There were 8 patients with PS and 6 patients with PF. SEP was
observed in 2 patients in the PS group. The risk of PS increased with the
duration of PD: 57% (8/14) > 5 years, 80% (4/5) > 8 years, and 100% (3/3) > 10
years. All patients in the PS group showed both peritoneal calcifications on
abdominal CT scan and poor ultrafiltration at the time of diagnoses. CONCLUSION:
Long-term PD was the important risk factor of SEP. If both peritoneal
calcification on abdominal CT scan and poor ultrafiltration are observed in a
patient on PD more than 5 years, a peritoneal biopsy should be performed. If PS
is detected, PD should be discontinued.
PMID- 11007378
TI - Peritoneal accumulation of AGE and peritoneal membrane permeability.
AB - BACKGROUND: In continuous ambulatory peritoneal dialysis (CAPD), the peritoneal
membrane is continuously exposed to high-glucose-containing dialysis solutions.
Abnormally high glucose concentration in the peritoneal cavity may enhance
advanced glycosylation end-product (AGE) formation and accumulation in the
peritoneum. Increased AGE accumulation in the peritoneum, decreased
ultrafiltration volume, and increased peritoneal permeability in long-term
dialysis patients have been reported. AIM: The purpose of the study was to
evaluate the relation between peritoneal membrane permeability and peritoneal
accumulation of AGE. METHODS: Peritoneal membrane permeability was evaluated by
peritoneal equilibration test (PET) using dialysis solutions containing 4.25%
glucose. Serum, dialysate, and peritoneal tissue levels of AGE were measured by
ELISA method using polyclonal anti-AGE antibody. Peritoneal biopsy was performed
during peritoneal catheter insertion [new group (group N), n = 18] and removal
[long-term group (group LT), n = 10]. Peritoneal catheters were removed due to
exit-site infection not extended into the internal cuff (n = 6) and
ultrafiltration failure (n = 4) after 51.6+/-31.5 months (13 - 101 months) of
dialysis. PET data obtained within 3 months after the initiation of CAPD or
before catheter removal were included in this study. Ten patients in group N and
4 patients in group LT were diabetic. Patients in group LT were significantly
younger (46.5+/-11.1 years vs 57.5+/-1.3 years) and experienced more episodes of
peritonitis (3.5+/-2.1 vs 0.2+/-0.7) than group N. RESULTS: Peritoneal tissue AGE
level in group LT was significantly higher than in group N, in both nondiabetic
(0.187+/-0.108 U/mg vs 0.093+/-0.08 U/mg of hydroxyproline, p < 0.03) and
diabetic patients (0.384+/-0.035 U/mg vs 0.152+/-0.082 U/mg of hydroxyproline, p
< 0.03), while serum and dialysate levels did not differ between the groups in
both nondiabetic and diabetic patients. Drain volume (2600+/-237 mL vs 2766+/-222
mL, p = 0.07) and D4/D0 glucose (0.229+/-0.066 vs 0.298+/-0.081, p < 0.009) were
lower, and D4/P4 creatinine (0.807+/-0.100 vs 0.653+/-0.144, p< 0.0001) and D1/P1
sodium (0.886+/-0.040 vs 0.822+/-0.032, p < 0.0003) were significantly higher in
group LT than in group N. On linear regression analysis, AGE level in the
peritoneum was directly correlated with duration of CAPD (r = 0.476, p = 0.012),
number of peritonitis episodes (r = 0.433, p = 0.0215), D4/P4 creatinine (r =
0.546, p < 0.027), and D1/P1 sodium (r = 0.422, p = 0.0254), and inversely
correlated with drain volume (r = 0.432, p = 0.022) and D4/D0 glucose (r = 0.552,
p < 0.0023). AGE level in the peritoneal tissue and dialysate were significantly
higher in diabetics than in nondiabetics in group LT, while these differences
were not found in group N. Serum AGE level did not differ between nondiabetics
and diabetics in either group N or group LT. Drain volume and D4/D0 glucose were
lower and D4/P4 creatinine and D1/P1 sodium higher in diabetics than in
nondiabetics in both groups. CONCLUSION: Peritoneal accumulation of AGE increased
with time on CAPD and number of peritonitis episodes, and was directly related
with peritoneal permeability. Peritoneal AGE accumulation and peritoneal
permeability in diabetic patients were higher than in nondiabetic patients from
the beginning of CAPD.
PMID- 11007379
TI - Left ventricular hypertrophy and clinical outcome in CAPD patients.
AB - OBJECTIVE: To determine the clinical outcome of left ventricular hypertrophy
(LVH) (left ventricular wall diastole thickness > or = 1.2 cm) detected by
echocardiography in nondiabetic, continuous ambulatory peritoneal dialysis (CAPD)
patients without dilated cardiomyopathy. DESIGN: A prospective, descriptive study
was conducted between 1 July 1995 and 31 January 1998. Patients were followed up
for 24 months. SETTING: Peritoneal dialysis unit in a medical school hospital.
PATIENTS AND METHODS: Baseline and yearly echocardiograms were carried out on 66
patients receiving CAPD. Cardiac death was assessed. LVH was correlated with
outcome. RESULTS: Of 66 nondiabetic CAPD patients without dilated cardiomyopathy,
20 had a normal echocardiogram (LV wall thickness < 1.2 cm), 21 had mild
hypertrophy, and 25 severe hypertrophy (LV wall thickness > 1.4 cm in diastole).
In the first two groups, 21% were admitted with congestive heart failure (CHF)
after starting dialysis. The 1-year cumulative survival was 85% among those with
mild hypertrophy and 91% in the normal group. In the group with severe
hypertrophy, 57% were admitted at least once with CHF, and the 1-year cumulative
survival was 56%. Eighty-two percent of those who died in the severe group, which
accounted for the significantly worse survival (p = 0.003), died from cardiac or
cerebrovascular causes, compared with none of those with a normal echocardiogram.
CONCLUSIONS: Severe LVH was found in a third of our CAPD patients and was
associated with a significantly high cardiovascular morbidity and mortality.
PMID- 11007380
TI - Insulin efficacy with a new bicarbonate/lactate peritoneal dialysis solution.
PMID- 11007381
TI - Prevalence of hepatitis G virus infection in a hemodialysis and a peritoneal
dialysis (CAPD) population.
PMID- 11007382
TI - Catheter cuff shaving using a novel technique: a rescue treatment for persistent
exit-site infections.
PMID- 11007383
TI - Peritoneal permeability of Asian Indian patients does not differ from that of non
Indian patients (in Toronto, Canada).
PMID- 11007384
TI - Literature. July-August 2000.
PMID- 11007385
TI - Breast cancer following breast reduction surgery in Sweden.
AB - Women undergoing breast reduction surgery have been reported to be at low
subsequent risk of breast cancer, especially when the surgery is performed after
age 40. To evaluate the age and time-related patterns of cancer risk following
surgical removal of breast tissue, we identified 31,910 women who underwent
breast reduction surgery from 1965 to 1993 in Sweden using hospital discharge
register data. There were 19,975 women (63 percent) under age 40 at surgery.
Linkages with Swedish registries for cancer, death, and emigration were based on
unique national registration numbers assigned to each Swedish resident. Cancer
incidence was contrasted with that expected in the general population based on
age- and calendar year-specific data from the nationwide cancer registry.
Overall, 161 incident breast cancers were identified during 238,765 person-years
of observation (mean, 7.5 years) compared with 223.9 expected (standardized
incidence ratio = 0.72; 95 percent confidence interval = 0.61 to 0.84). The
reduction in risk of breast cancer was most pronounced for women whose operations
were performed after age 50 (SIR = 0.57) and for those followed for more than 5
years (SIR = 0.68). Among women operated on before age 40, risk was
nonsignificantly elevated within the first 5 years after surgery (SIR = 1.47; 95
percent CI = 0.89 to 2.30) but tended to be reduced thereafter (SIR = 0.80; 95
percent CI = 0.55 to 1.13). The magnitude of the reduction in risk thus appears
directly related to age at surgery. Women followed for an average of 7.5 years
after bilateral breast reduction surgery, were at a statistically significant 28
percent decreased risk of breast cancer. The current study is thus consistent
with a protective effect following partial removal of breast glandular tissue.
PMID- 11007386
TI - Modified autogenous latissimus breast reconstruction and the box top nipple.
AB - During the past 3 years, the authors have been using the modified autogenous
latissimus myocutaneous flap (MALF) for breast reconstruction in increasing
numbers because of occasional patient and surgeon dissatisfaction with other
methods of breast reconstruction. They have found this method to have
unprecedented reliability, making it preferable to other forms of reconstruction
in many patients. Considering the very low morbidity, the high patient
satisfaction, and current economic factors, the authors are strong advocates of
this form of reconstruction. A procedural outline proposed by McCraw and
coworkers is followed, with some useful modifications. An elliptical transverse
skin paddle is centered over the back fat roll. The area of the skin ellipse
measures approximately 8 +/- 2 cm vertically and 30 +/- 5 cm transversely. After
making the skin incision, a feathering technique is used in all directions
through the fatty layer overlying the latissimus and in the tissue beyond the
anteroposterior borders of the latissimus (not beyond 5 cm from the skin
incision). By means of feathering, the shape of a breast mound can be created in
the allowable tissue supported by the latissimus. A 180-degree rotation of the
flap allows dependentvenous drainage and more bulk in the inferior outer
quadrant, where it is needed. In the current series of 47 modified autogenous
latissimus breast reconstructions, seromas were common. Other complications
included one wound infection, one ulnar neuropraxia, and one fat necrosis. There
were no flap necroses (partial or complete) or hematomas. The rarity of
complications supports the use of this technique in selected patients. An
innovative new technique for nipple reconstruction is also described. The "box
top technique" of nipple reconstruction consists of four deepithelialized local
flaps covered with a skin graft from the groin.
PMID- 11007387
TI - Determinants of patient satisfaction in postmastectomy breast reconstruction.
AB - In today's increasingly competitive health care marketplace, consumer
satisfaction has become an important measure of quality. Furthermore, measures of
satisfaction with treatment inteerventions are influential factors in determining
patients' and payers' choices of health care. This study sought to evaluate
satisfaction with postmastectomy breast reconstruction and to assess the effects
of procedure type and timing on patient satisfaction. As part of the Michigan
Breast Reconstruction Outcome Study, patients undergoing first-time mastectomy
reconstruction were prospectively evaluated, including cohorts of women choosing
expander/implant, pedicle TRFAM flap, and free TRAM flap procedures.
Preoperatively and 1 year postoperatively, participants completed a questionnaire
that collected a variety of health status information. The postoperative
questionnaire had an additional seven items assessing both general satisfaction
with reconstruction (five items) and aesthetic satisfaction (two items) as
separate subscales. Patients were asked to respond to each item using a five
point Likert scale. Item responses ranged from 1, indicating high satisfaction,
to 5, reflecting low satisfaction. In the data analysis, only patients responding
with a 1 or 2 for all of the items within a subscale were classified as
"satisfied" for the subscale. To assess the effects of procedure type (implant,
pedicle TRAM flap, and free TRAM flap) and timing (immediate versus delayed) on
satisfaction and to control for possible confounding effects from other
independent variables, multiple logistic regression was employed. In our
analysis, odds ratios and associated 95 percent confidence intervals were
calculated for each independent variable in the regression. Statistical
significance was designated at the p < or = 0.05 level. A total of 212 patients
were followed during the period of 1994 to 1997, including 141 immediate and 71
delayed reconstructions. The study population consisted of 49 expander/implant,
102 pedicle TRAM flap, and 61 free TRAM flap reconstruction patients. The
analysis showed a significant association between procedure type and patient
satisfaction. TRAM flap patients (both free and pedicle) appeared to have
significantly greater general and aesthetic satisfaction compared with
expander/implant patients (p = 0.03 and 0.001, respectively). Furthermore,
pedicle TRAM flap patients were more aesthetically satisfied than those with free
TRAM flaps (p = 0.072). The other independent variables of age and procedure
timing did not appear to significantly affect either general or aesthetic
satisfaction. However, preoperative physical activity was positively correlated
with general satisfaction at the p = 0.034 level. The choice of procedure seems
to have a significant effect on both aesthetic and general patient satisfaction
with breast reconstruction. In this study, autogenous tissue reconstructions
produced higher levels of patient aesthetic and general satisfaction compared
with implant techniques. Pedicle and free TRAM flap patients do not seem to
differ significantly in general satisfaction. However, women receiving pedicle
TRAM flaps reported greater aesthetic satisfaction compared with patients
undergoing free TRAM flaps. Furthermore, patient age and procedure timing may not
have an effect on patient satisfaction with breast reconstruction.
PMID- 11007388
TI - A new technique of scarless expanded forehead flap for reconstructive surgery.
AB - The forehead flap is an ideal flap for reconstructive surgery, especially for
that involving reconstruction of the face and neck. However, it is usually
limited to use in nasal reconstruction, even when performed in conjunction with
tissue expansion, because of the severe visible morbidity of the donor site. In
this article, the author discusses his development of a new technique of forehead
flap, performed in conjunction with tissue expansion, for reconstructive surgery
without visible scarring at the donor site. The technique involved positioning a
tissue expander in the forehead pocket under the occipitofrontal muscle and
serially inflating the expander over a period of approximately 4 to 6 weeks.
Thereafter, an expanded forehead flap was created from the frontal hairline area
on the basis of the location of the superficial temporal vessels and transferred
into 16 recipient sites in 13 patients as an island flap (n = 8), a free flap (n
= 1), or a local random flap (n = 7). The donor site was closed directly into the
frontal hairline, without any visible scar. With the author's experience in the
use of the island flap for nasal, facial, and neck reconstruction and of the free
flap for reconstruction in the extremities, the flap could be as large as 8 x 18
cm without inducing flap necrosis or problems with donor-site closure. All
patients (n = 13) had acceptable donor-site aesthetic results, without visible
scarring. The results indicate that the flap could be a safe, ample, and color
matched flap for reconstruction of the face and neck and could also diminish
donor-site morbidity to a minimum, without an unsightly visible scar.
Furthermore, the flap could be formed into a customized free flap, with the above
mentioned advantages, to be transferred to any part of the body.
PMID- 11007389
TI - Ten-year review of a prospective randomized controlled trial of textured versus
smooth subglandular silicone gel breast implants.
AB - Although textured silicone breast implants have been shown to reduce the
incidence of capsular contracture, there is little evidence if this effect is
maintained in the long term. It has been 10 years since the double-blind
randomized trial in which 53 patients received either Mentor smooth (26) or
textured silicone gel implants (27). Of the 14 patients who were not known to
have developed a contracture in the smooth group, 11 were reviewed. Three had
bilateral contractures. In the textured group, 18 of the 24 patients not known to
have contractures were reviewed. None had developed contractures. At 10 years,
the incidence of capsular contracture was 65 percent of patients with smooth
implants (an increase of 6 percent on the 3-year results) and 11 percent for the
textured implant patients (no change on the 3-year results). A database
containing the details of 1100 patients reinforces these results by examining the
differences in contracture rates of textured, smooth, and polyurethane-coated
implants. The effect of submuscular placement on reducing contracture rates
regardless of texturing is discussed, as is the apparent increase in capsular
contracture in patients who smoke.
PMID- 11007390
TI - Recurrence of subglandular breast implant capsular contracture: anterior versus
total capsulectomy.
AB - The objective of this study was to determine whether the type of capsulectomy,
anterior or total, affects the recurrence of capsular contracture around
subglandular silicone-gel breast implants. A retrospective analysis was performed
of patients who underwent either anterior or total capsulectomy for Baker grade 3
or 4 subglandular capsular contracture in our unit. All patients were invited to
a review clinic where their capsular status was assessed. There were 100 anterior
disc capsulectomies in 60 patients between 1988 and 1997 and 99 total
capsulectomies in 60 patients between 1990 and 1998. The follow-up in the former
group was a median of 7 years and mean 6.9 years, compared with median 2.5 and
mean 3.1 years in the latter group. Eighty-six percent of the implants removed
from both groups at capsulectomy were smooth-walled gel-filled implants. Sixty
nine breasts in the anterior group received textured gel implants at
capsulectomy; the remaining 31 received polyurethane-coated Meme implants. In the
total capsulectomy group, all but two breasts (one patient) received textured gel
implants. After review, the capsular status was known in 80 percent of the
anterior and 92 percent of the total capsulectomy group. The review clinic found
eight new contractures in five patients to have developed in the anterior
compared with none in the total group. Recurrent contractures affected 50 percent
of patients (46 percent of breasts) in the anterior and 11 percent of patients
(10 percent of breasts) in the total capsulectomy group. Kaplan-Meier survival
analysis was applied to the data. By including only patients who received
textured gel implants at capsulectomy, the Logrank found a statistical difference
between the two treatment groups (0.01 < p < 0.5). We believe that this study
provides some evidence that total capsulectomy for subglandular silicone breast
implant capsular contracture results in a lower capsular recurrence than anterior
disc capsulectomy. The pattern and risk of recurrence after total capsulectomy
and exchange for a modern textured prosthesis appear to approach those following
primary augmentation.
PMID- 11007391
TI - Lip reconstruction following Mohs' surgery: the role for composite resection and
primary closure.
AB - Surgical outcomes and patient satisfaction with composite resection and primary
closure for the management of upper-lip defects following Mohs' surgery were
evaluated. Twenty-seven patients underwent upper-lip reconstruction following
Mohs' surgery from 1993 to 1997. Twelve of these patients were selected for this
report based on adequate follow-up examinations and photographs. There were nine
women and three men with a mean age of 46 years (range, 33 to 70 years). Eleven
patients underwent Mohs' surgery for basal cell carcinoma and one patient for
squamous cell carcinoma of the upper lip. The defects varied in size and
location, often extending beyond a single aesthetic subunit. The reconstruction
was performed an average of 7 days after Mohs' surgery (range, 1 to 23 days). In
50 percent of the cases, a full-thickness excision was performed, which included
orbicularis oris and inner-lip mucosa. The functional results were graded as near
normal to normal in all cases. There were no observed changes in oral continence,
eating or speech. Two patients experienced numbness medial to the operative site,
but this had no adverse affect on lip function. The aesthetic results were graded
as very good to excellent in all cases. Eleven of the 12 patients were satisfied
with their lip appearance and function. Conventional wisdom dictates that during
reconstruction of upper-lip defects, one should attempt to maintain a majority of
the uninvolved tissue for the best result. Although these techniques result in
wound closure, they fail to consider lip aesthetics. By using a vertically
oriented composite resection of the tipper lip with the additional resection of
uninvolved tissue, normal lip architecture is maintained. In our experience, this
results in a superior aesthetic and functional result.
PMID- 11007392
TI - Abdominal wall closure after intestinal transplantation.
AB - Successful surgical closure of the abdominal wall after either combined or
isolated intestinal transplantation may present a challenging dilemma for the
plastic and reconstructive surgeon because of the following factors: restricted
volume of the recipient abdominal cavity; donor-recipient size discrepancies as
expressed by the donor to recipient weight ratio; and significant intraoperative
edema. The purpose of this investigation is to present clinical experience with
51 consecutive patients who underwent a total of 57 sequential intestinal
transplantations at the University of Miami-Jackson Memorial Hospital. A
retrospective chart review of 36 pediatric (63 percent) and 21 adult (37 percent)
transplantations was performed. Age of the pediatric population ranged from 1
month to 13 years (mean, 2.4 years) and of the adult population from 22 to 55
years (mean, 33.5 years). Several diagnostic classifications necessitated organ
transplantation. Because of insufficient donor graft size for the recipient
abdominal cavity in 19 transplantations (33 percent), several technical
modifications were used to achieve anatomic and functional abdominal wall closure
in all patients. In summary, the plastic and reconstructive surgeon should have a
significant role in the comprehensive planning and management of abdominal wall
closure in this challenging group of patients.
PMID- 11007393
TI - Treatment of diabetic neuropathy by decompression of the posterior tibial nerve.
AB - A series of 58 operations on 36 patients were performed for decompression of the
posterior tibial nerve for the treatment of diabetic neuropathy. Preoperative
symptoms included lack of sensation, pain, or both. Eleven of the 36 patients had
neurotrophic ulcers, which were treated simultaneously. The operation was found
to be effective for relief of pain in 24 of the 28 patients with that complaint
(86 percent). Restoration of sensation was less consistent with improvement noted
in 18 of the 36 patients (50 percent). The follow-up period ranged from 12 to 84
months (mean, 32 months) and five patients had some degree of recurrent symptoms.
No patient has developed a new ulcer after nerve decompression. Wound
complications were minimal (12 percent), even though ulcers were treated
simultaneously. No patient required surgical treatment for the decompression
incision, although one did require hospital admission for treatment of a wound
infection. In general, the procedure seemed to be a worthwhile treatment, which
should be considered ill selected diabetics with symptomatic neuropathy.
PMID- 11007394
TI - Results of decompression of peripheral nerves in diabetics: a prospective,
blinded study.
AB - Diabetic neuropathy traditionally is considered progressive and irreversible and
will result in lower extremity ulceration and amputation in a segment of the
diabetic population, despite the best efforts to control serum glucose levels.
Restoration of sensation to the diabetic may prevent these complications of
neuropathy. The present study was designed to evaluate whether decompression of a
peripheral nerve at a known site of anatomic narrowing can restore sensibility to
that nerve in the diabetic. Twenty diabetic patients ( 14 type I, 6 type II, with
a mean duration of diabetes of 14.8 years) had surgical decompression of a median
nerve at the wrist and an ulnar nerve at the elbow, or a decompression of the
posterior tibial nerve at the ankle (total of 31 nerves). A therapist, in a
manner blind to the operative site, evaluated two-point discrimination in the
pulp of the appropriate digit. The postoperative sensibility was compared with
that of the nontreated, contralateral extremity. At a mean of 23.3 months, 69
percent of the lower-extremity nerves and 88 percent of the upper-extremity
nerves (79 percent overall) had improvement in sensibility. In comparison, 32
percent of the control (not decompressed) contralateral nerves had measurable
progression of neuropathy. The hypothesis that decompression of a peripheral
nerve in the diabetic will improve sensibility was confirmed at the p < 0.001
level.
PMID- 11007395
TI - Forefoot reconstruction by reversed island flaps in diabetic patients.
AB - Soft-tissue coverage of the foot is often difficult, especially when the distal
third of the foot (dorsal or plantar aspects) is involved. The clinical situation
can be further complicated when diabetic patients are affected by painful and
unstable wounds of this kind because of the familiar phenomenon of vasculopathy.
The purpose of this study was to evaluate the possibility of using distally based
foot flaps to cover forefoot defects in diabetic patients. Preoperative selection
of patients was the key to this study; those who had other major disease, chronic
infection, bone involvement, and/or insufficient foot vascularization were
excluded from the study. The authors report a series of 12 diabetic patients in
whom the reconstruction of medium-sized defects (ranging from 1.5 x 2.0 cm to 3.0
x 7.0 cm) of the forefoot was performed using distally based dorsalis pedis flaps
or medial plantar flaps. The transferred flaps survived and adapted well to the
defects, except for one flap in a patient who had a slight venous insufficiency
at outset. Wearing their own footwear, patients could walk after 20 to 30 days.
After the follow-up period (3 months to 3 years), no skin breakdown in the
treated areas was observed. Temporary donor-site pain was reported by medial
plantar flap patients, and partial skin graft loss at the donor site occurred in
some of the dorsalis pedis patients. The authors suggest that in selected cases,
medium-sized soft-tissue defects involving the dorsal aspects or the weight
bearing areas of the diabetic foot can be successfully covered with distally
based island flaps.
PMID- 11007396
TI - A reverse ulnar hypothenar flap for finger reconstruction.
AB - A reverse-flow island flap from the hypothenar eminence of the hand was applied
in 11 patients to treat palmar skin defects, amputation injuries, or flexion
contractures of the little finger. There were three female and eight male
patients, and their ages at the time of surgery averaged 46 years. A 3 x 1.5 to 5
X 2 cm fasciocutaneous flap from the ulnar aspect of the hypothenar eminence,
which was located over the abductor digiti minimi muscle, was designed and
transferred in a retrograde fashion to cover the skin and soft-tissue defects of
the little finger. The flap was based on the ulnar palmar digital artery of the
little finger and in three patients was sensated by the dorsal branch of the
ulnar nerve or by branches of the ulnar palmar digital nerve of the little
finger. Follow-up periods averaged 42 months. The postoperative course was
uneventful for all patients, and all of the flaps survived without complications.
The donor site was closed primarily in all cases, and no patient complained of
significant donor-site problems. Satisfactory sensory reinnervation was achieved
in patients who underwent sensory flap transfer, as indicated by 5 mm of moving
two-point discrimination. A reverse island flap from the hypothenar eminence is
easily elevated, contains durable fasciocutaneous structures, and has a good
color and texture match to the finger pulp. This flap is a good alternative for
reconstruction of palmar skin and soft-tissue defects of the little finger.
PMID- 11007397
TI - The boomerang flap in managing injuries of the dorsum of the distal phalanx.
AB - Finding an appropriate soft-tissue grafting material to close a wound located
over the dorsum of a finger, especially the distal phalanx, can be a difficult
task. The boomerang flap mobilized from the dorsum of the proximal phalanx of an
adjacent digit can be useful when applied as an island pedicle skin flap. The
vascular supply to the skin flap is derived from the retrograde perfusion of the
dorsal digital artery. Mobilization and lengthening of the vascular pedicle are
achieved by dividing the distal end of the dorsal metacarpal artery at the
bifurcation and incorporating two adjacent dorsal digital arteries into one. The
boomerang flap was used in seven individuals with injuries involving the dorsal
aspect of the distal phalanx over the past year. Skin defects in all patients
were combined with bone,joint, or tendon exposure. The authors found that the
flap was reliable and technically simple to design and execute. This one-step
procedure preserves the proper palmar digital artery to the fingertip and has
proven valuable for the coverage of wide and distal defects because it has the
advantages of an extended skin paddle and a lengthened vascular pedicle. When
conventional local flaps are inadequate, the boomerang flap should be considered
for its reliability and low associated morbidity.
PMID- 11007398
TI - Buried penis release in adults with suction lipectomy and abdominoplasty.
AB - The buried penis in adults who had substantial weight gain was treated with a
combination of suction lipectomy of the abdomen and pubic area and the release of
the suspensory ligament of the penis and with abdominoplasty with suture
anchoring of the pubic and penile skin base dermis to the rectus fascia
superiorly. This procedure was performed in 11 patients over the past 10 years
with satisfactory results. One patient required additional excess skin excision
from the side of the pubic and scrotal area to improve the results.
PMID- 11007399
TI - Can dog-ear formation be decreased when an S-shaped skin resection is used
instead of a spindle skin resection? A three-dimensional analysis of skin surgery
techniques using the finite element method.
AB - Dog-ear formation is often unavoidable with resection and suturing of the skin,
including spindle excision. Regarding dog-ear formation after basic spindle skin
resection during removal of a round tumor of the skin, we quantitatively analyzed
the frequency of dog-ear formation with respect to the following three
techniques: previous spindle skin resection, S-shaped skin resection, which has
been experientially considered to induce limited deformity, and mosque-shaped
skin resection for control. To date, by using paper models or sponges, various
techniques of skin resection have been simulated in the field of plastic surgery.
In the present study, we performed three-dimensional simulation and analyzed
three different techniques of skin resection by using the finite element method.
As a result, image simulation demonstrated that the frequency of dog-ear
formation was limited by S-shaped, spindle, and mosque-shaped skin resection, in
descending order.
PMID- 11007400
TI - A molecular analysis of the isolated rat posterior frontal and sagittal sutures:
differences in gene expression.
AB - Although it is one of the most commonly occurring craniofacial congenital
disabilities, craniosynostosis (the premature fusion of cranial sutures) is
nearly impossible to prevent because the molecular mechanisms that regulate the
process of cranial suture fusion remain largely unknown. Recent studies have
implicated the dura mater in determining the fate of the overlying cranial
suture; however, the molecular biology within the suture itself has not been
sufficiently investigated. In the murine model of cranial suture fusion, the
posterior frontal suture is programmed to begin fusing by postnatal day 12 in
rats (day 25 in mice), reliably completing bony union by postnatal day 22 (day 45
in mice). In contrast, the sagittal suture remains patent throughout the life of
the animal. Using this model, this study sought to examine for the first time
what differences in gene expression--if any--exist between the two sutures with
opposite fates. For each series of experiments, 35 to 40 posterior frontal and
sagittal suture complexes were isolated from 6-day-old Sprague-Dawley rat pups.
Suture-derived cell cultures were established, and ribonuicleic acid was derived
from snap-frozen, isolated suture tissue. Results demonstrated that molecular
differences between the posterior frontal and sagittal suture complexes were
readily identified in vivo, although these distinctions were lost once the cells
comprising the suture complex were cultured in vitro. Hypothetically, this change
in gene expression resulted from the loss of the influence of the underlying dura
mater. Significant differences in the expression of genes encoding extracellular
matrix proteins existed in vivo between the posterior frontal and sagittal
sutures. However, the production of the critical, regulatory cytokine
transforming growth factor beta-1 was equal between the two suture complexes,
lending further support to the hypothesis that dura mater regulates the fate of
the overlying cranial suture.
PMID- 11007401
TI - Crossover replantation and fillet flap coverage of the stump after ectopic
implantation: a case of bilateral leg amputation.
AB - A successful case of crossover replantation of the left foot to the stump of the
right leg and temporary ectopic implantation of the right amputated foot on the
forearm is described. The ectopically implanted right foot was used as a free
fillet flap for the late reconstruction of the left leg stump. At the latest
follow-up examination, 18 months after the accident, the patient was able to walk
independently with a prosthesis on the stump of the left leg. Both the cross
replanted foot and the free filleted foot flap, used for the reconstruction of
the left leg stump, have maintained adequate protective sensation. The importance
of utilization of amputated parts for functional reconstruction is stressed.
Crossover replantations and ectopic implantations should be considered in
bilateral amputations for the salvage of at least one extremity.
PMID- 11007402
TI - Medial plantar flap based distally on the lateral plantar artery to cover a
forefoot skin defect.
AB - The authors report a simple, single-step procedure to promote the distal transfer
of the instep island flap for coverage of the submetatarsal weight-bearing zone.
First described in 1991 by Martin et aI, this procedure remained unknown. As
opposed to the medial plantar flap, this technique proposes an instep island flap
based on the lateral plantar artery. The inflow and outflow of blood is assured
by the anastomosis between the dorsalis pedis and lateral plantar vessels. This
approach allows for the transfer of similar tissue and provides adequate coverage
of the weight-bearing zone of the distal forefoot.
PMID- 11007403
TI - Minimally invasive approach to familial multiple lipomatosis.
AB - Thirty-five abdominal wall lipomas were removed from a patient with familial
multiple lipomatosis using a minimally invasive approach in a cost-effective,
reliable, and cosmetically pleasing manner. The surgical technique used is
described in this case report. Clinical findings and prior excisions provided the
preoperative diagnosis. The abdominal wall was dissected through two small,
vertical midline incisions in the suprafascial plane with the aid of a lighted
breast retractor. A complete excision of all palpable lipomas was achieved with
this approach. The patient had excellent cosmetic results with minimal
postoperative scarring.
PMID- 11007404
TI - Treatment of finger avulsion injuries with innervated arterialized venous flaps.
AB - Complete degloving injury of the digits not amenable to revascularization may
leave poor cosmetic and functional results. We used innervated venous flaps from
the dorsum of the foot in two patients with traumatic finger degloving injuries.
All the flaps successfully provided coverage over the denuded fingers. Good
sensation and nearly full rage of motion of the fingers were obtained. There were
no donor-site problems. The advantages of this flap are preservation of a major
artery of the donor site, easy elevation without deep dissection, and providing a
thin, nonbulky tissue and good sensation. The innervated arterialized venous flap
is a useful method that provides functional and cosmetic coverage to the severe
avulsion injury of the finger.
PMID- 11007405
TI - Establishing cleft malformation surgery in developing nations: a model for the
new millennium.
AB - This three-stage model outlines a safe and effective method for achieving a local
cleft board in a developing region. Maintaining local culture and guaranteeing
patient safety are paramount concerns. Success is rooted in the constant
assessment and recognition of negative forces, including misdirection and
stagnation. The key factors are the identification of an interested local host
and a source of funding as the site evolves toward independence. As of June 30,
2000, 501 cases had been performed independently and free of charge by the host
healthcare provider in Nepal. There had been no major morbidities or mortalities.
PMID- 11007406
TI - Facial sensibility testing: a clinical update.
PMID- 11007407
TI - Efficacy of preoperative decontamination of the oral cavity.
AB - This two-part study consisted of: (1) a survey to assess current practice
patterns, and (2) an experiment designed to assess the results of varying
intraoral preparations. A 48 percent response rate was obtained from the survey
of the 318 active members of the American Society of Maxillofacial Surgeons. This
survey demonstrated that significant controversy continues regarding the efficacy
of preoperative decontamination of the oral cavity. This prospective, randomized
experimental study of 30 patients (saline, 10; povidone-iodine, 10; no
preparation, 10) demonstrates a significant and sustained reduction of both
anaerobic and aerobic bacteria after intraoral preparation with povidone-iodine
solution but not saline. The patient's age, use of preoperative intravenous
cephalosporin, and type and length of procedure did not influence the
postoperative bacterial counts. Although none of the patients in this study
developed an infection, recommendations are provided for standardized
preoperative treatment of the oral cavity.
PMID- 11007408
TI - The FDA approves saline-filled breast implants: what does this mean for our
patients?
PMID- 11007409
TI - Management of the bulbous nose.
AB - "Bulbous nose" is a term patients often use to describe a "ball" on the end of
their nose. This ball can be caused by the abnormal anatomy of alar cartilage or
by the overlying soft-tissue coverage. The purpose of this article is to analyze
the different causes of bulbous noses and their treatment options. An analysis
was done based on four decades of experience and long-term follow-up. We included
10 patients for our discussion. The relationship of the tip to the vault must be
analyzed, because it can create optical illusions. For instance, a low bridge
makes the tip appear larger; therefore, a bulbous nose may be relative.
Similarly, excessive narrowing of the nasal base by alar wedges makes the tip
appear wider. Intrinsic causes of a bulbous nose include skin, subcutaneous
tissue (including the nasal superficial musculoaponeurotic system, ligaments, and
fat), and the shape and direction of the individual crus. Nasal skin varies as to
volume and ability to contract; therefore, the shape, direction, or divergence of
the individual crura cannot undergo unlimited modifications. There are several
surgical possibilities for a given problem. Making the diagnosis of the
underlying abnormal anatomy is the most important step; then the most appropriate
operation can be selected. Struts, sutures, resection, dome division, and/or
dorsal augmentation are all viable options for the management of the bulbous
nose.
PMID- 11007410
TI - The use of resorbable spacers for nasal spreader grafts.
AB - The concept and technique of the use of resorbable synthetic material for nasal
spreader grafts are presented. The material is felt to be particularly useful in
revision rhinoplasty, in which the likelihood of internal valve collapse is high
and the septum (the most common source of material for spreader grafts) often has
already been harvested. The material used is a commercially available polymer of
polylactic and polyglycolic acid, Lactosorb. It is supplied as a mesh sheet that
can be cut to an appropriate size for spreader grafts. Although the material
absorbs after approximately 12 months, it is believed that this is sufficient
time for the upper lateral cartilages to be stabilized by fibrosis in their new
position and to maintain the appropriate internal valve angle. This material was
used on 10 patients with valvular collapse undergoing secondary rhinoplasty. In
follow-up observations ranging from 12 to 18 months, there has been no recurrence
of airway obstruction.
PMID- 11007411
TI - In situ split costal cartilage graft harvesting through a small incision using a
gouge.
AB - A costal cartilage graft is one of the most useful materials in reconstructive
plastic surgery. In this article, a technique of in situ split costal cartilage
graft harvesting through a small incision (2 to 3 cm) using a gouge is described.
The technique used has many advantages: it is a simple technique, is easy to
learn, and can be performed quickly through a small incision. By avoiding
complete costal cartilage graft harvesting, the associated potential
complications such as pleural perforation, chest wall deformities, long-lasting
postoperative pain, and incisional scar length are reduced. This technique will
be useful in selected cases for which a complete block of costal cartilage graft
is not needed.
PMID- 11007412
TI - Surgical treatment of the senile upper lip.
AB - Aesthetic changes in the aging upper lip constitute a troublesome problem for
modern women. During the process of aging, the following alterations appear in
the upper lip: (1) vertical wrinkles, (2) reduction in height of the vermilion
border along with lengthening of the skin area of the lip, and (3)
"disappearance" of the Cupid's bow. In 1993, Guerrissi and Sanchez described a
surgical technique that allowed them to correct the effects of these senile
changes in 19 patients. With the use of this surgical technique, a strip of skin
on the vermilion border was deepithelialized. The remaining dermal flap was
buried in the pocket, which was performed by undermining the superior third of
the skin of the upper lip. The short-term results were satisfactory, although a
slight reduction in height of the vermilion border and a decrease in the
thickness of the lip were observed in five patients (26 percent) 4 years
postoperatively. Beginning in 1994, the authors began using a new approach
combining dermal flap reshaping with simultaneous lip augmentation using dermal
fat grafts, Gore-Tex (W. L. Gore and Associates, Flagstaff, Ariz.) or AlloDerm
(LifeCell Corp., Branchburg, NJ.). No serious or definitive complications were
observed. Scars on the vermilion border were not conspicuous. A peel was
necessary at the same time for complete elimination of rhytids. With this method,
both the patients and the surgeons were satisfied with the results.
PMID- 11007413
TI - Privacy: wanted or unwanted?
PMID- 11007414
TI - Rejuvenation of the midface.
PMID- 11007415
TI - Facial palsy after abdominal liposuction.
PMID- 11007416
TI - Hospital-acquired pressure ulcers: an epidemic.
PMID- 11007417
TI - Reducing the hazard of burns and bovie pads.
PMID- 11007418
TI - Dermoid cyst on the auriculotemporal area.
PMID- 11007419
TI - A surgical technique for the correction of all types of prominent ears?
PMID- 11007420
TI - Frontal sinus expansion from an uncommon cause.
PMID- 11007421
TI - Intranasal Kirschner Wire Splinting of nasal fractures.
PMID- 11007422
TI - Alloderm lip augmentation.
PMID- 11007423
TI - New problems in precertifying breast reduction surgery.
PMID- 11007424
TI - Desmoid tumor of the hand.
PMID- 11007425
TI - The development of the distally based radial forearm flap in hand reconstruction
with preservation of the radial artery.
PMID- 11007426
TI - Preputial neurofibroma with hypospadias.
PMID- 11007427
TI - A nonanimal model for microsurgical training with adventitial stripping.
PMID- 11007428
TI - Plastic surgery at the turn of the century.
PMID- 11007429
TI - Primum non nocere.
PMID- 11007431
TI - W.I.N.: what's in a name?
PMID- 11007430
TI - Patient selection in cosmetic surgery.
PMID- 11007432
TI - New approaches to molecular profiling of tissue samples.
PMID- 11007433
TI - Reconstruction of axial tomographic high resolution data from confocal
fluorescence microscopy: a method for improving 3D FISH images.
AB - Fluorescent confocal laser scanning microscopy allows an improved imaging of
microscopic objects in three dimensions. However, the resolution along the axial
direction is three times worse than the resolution in lateral directions. A
method to overcome this axial limitation is tilting the object under the
microscope, in a way that the direction of the optical axis points into different
directions relative to the sample. A new technique for a simultaneous
reconstruction from a number of such axial tomographic confocal data sets was
developed and used for high resolution reconstruction of 3D-data both from
experimental and virtual microscopic data sets. The reconstructed images have a
highly improved 3D resolution, which is comparable to the lateral resolution of a
single deconvolved data set. Axial tomographic imaging in combination with
simultaneous data reconstruction also opens the possibility for a more precise
quantification of 3D data. The color images of this publication can be accessed
from http://www.esacp.org/acp/2000/20-1/heintzmann.++ +htm. At this web address
an interactive 3D viewer is additionally provided for browsing the 3D data. This
java applet displays three orthogonal slices of the data set which are
dynamically updated by user mouse clicks or keystrokes.
PMID- 11007434
TI - Heterogeneous chromosomal aberrations in intraductal breast lesions adjacent to
invasive carcinoma.
AB - There is evidence that breast cancer is a heterogeneous disease phenotypically as
well as molecular biologically. So far, heterogeneity on the molecular biological
level has not been investigated in potential precursor lesions, such as ductal
hyperplasia (DH) and ductal carcinoma in situ (DCIS). In this study we applied
comparative genomic hybridization (CGH) to formalin-fixed, paraffin-embedded
breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC), to
screen these potential precursor lesions for whole genomic chromosomal
imbalances. Laser-microdissection was used to select pure cell populations from
the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR
(DOP-PCR) and further processed for CGH analysis. Investigating multiple samples
(n = 25) from four patients we found an average of 5.6 +/- 0.9 (mean +/- SEM)
chromosomal imbalances already present in DH. In the twelve DCIS lesions an
average of 10.8 (+/- 0.9) aberrations was identified with 14.8 (+/- 0.8)
aberrations in the four adjacent IDC lesions. The increasing number of
chromosomal changes in parallel with the histopathological sequence corroborate
the hypothesis, that the carcinomas may have developed through a sequential
progression from normal to proliferative epithelium and eventually into
carcinoma. However, heterogeneous results were identified in the multiple samples
per entity from the same patient, demonstrated mainly in the DCIS samples in the
chromosomal regions 6p, 9p, 11q, 16p and 17q, in the DH samples by 3p, 16p and
17q. This heterogeneous findings were most pronounced within the DH and was less
in the DCIS and IDC samples. The only aberration consistently found in all
samples-even in all DH sample-was amplification of the 20q13 region. Our results
demonstrate, that the applied combination of laser-microdissection, DOP-PCR and
CGH, may serve to analyse breast carcinogenesis pathways in suitable histological
material. However, so far, it is unclear how to handle heterogeneous results and
these make identification of relevant changes more difficult. Setting a threshold
and evaluating only those chromosomal changes which are present in a majority of
samples may be one possibility. This involves however, the risk that infrequent
but possibly significant aberrations may be missed. Figures on
http://www.esacp.org/acp/2000/20-1/aubele. htm.
PMID- 11007435
TI - Evaluation of c-erbB-2 overexpression and Her-2/neu gene copy number
heterogeneity in Barrett's adenocarcinoma.
AB - Amplification of the Her-2/neu gene is accompanied by overexpression of its cell
surface receptor product, c-erbB-2 protein. To investigate the degree of
intratumoural heterogeneity we applied immunohistochemistry in primary Barrett's
adenocarcinoma (BCA) (n = 6) and dysplasia adjacent to the carcinoma (n = 4). In
addition, fluorescence in situ hybridisation (FISH) was performed in primary BCA
(n = 5) and dysplastic areas (n = 4). For an objective evaluation digital image
analysis and laser scanning microscopy were used. Five of six BCA showed a marked
intratumoral heterogeneous staining pattern ranging from areas in which the
tumour cells were negative or faintly positive to tumour areas with a strong
staining of the entire membrane. Among the two dysplastic areas also a
heterogeneous staining pattern was observed. FISH analysis revealed marked
heterogeneity of intratumoral gene copy number changes in all BCA showing
populations with different fractions of cells with polysomy, low level
amplification and high level amplification. One dysplasia showed a minor
population with Her-2/neu signal clusters. In conclusion, we observed marked
intratumoural heterogeneity of c-erbB-2 protein overexpression and Her-2/neu gene
copy number in the majority of the primary BCA analyzed. Digital image analysis
and laser scanning microscopy were helpful in quantifying the variations in
protein expression and DNA copy number in individual tumour cells. The observed
heterogeneity could hamper the exact diagnostic determination of the c-erbB-2
status in small biopsies and possibly influence the effectiveness of a potential
c-erbB-2 targeting therapy. Figures on http://www.esacp.org/acp/2000/20
1/walch.htm+ ++.
PMID- 11007436
TI - Combining dynamic and static robotic telepathology: a report on 184 consecutive
cases of frozen sections, histology and cytology.
AB - The aim of this paper is to describe the experiments carried out to evaluate the
diagnostic efficacy of a dynamic-robotic telepathology system for the delivery of
pathology services to distant hospitals. The system provides static/dynamic
features and the remote control of a robotized microscope over 4 ISDN lines. For
evaluation purposes, 184 consecutive cases of frozen sections (60),
gastrointestinal pathology (64), and urinary cytology (60) have been diagnosed at
a distance using the system, and the telediagnosis obtained in this way has been
compared with the traditional microscopic diagnosis. Diagnostic agreement ranged
from 90% in urinary cytology to 100% in frozen sections. The results obtained
suggest that such a system can be considered a useful tool for supporting the
pathology practice in isolated hospitals.
PMID- 11007437
TI - Nuclear DNA content and chromatin pattern of rat rhabdomyosarcoma cell sublines
with different metastatic potentials.
AB - There is a constant need of features able to characterize potentially metastatic
cells among the heterogeneous cell subpopulations which constitute a tumor. Image
cytometry of metastatic tumor cells give rise to variable results, partly because
of a heterogeneous origin of cells, or potential drug effects. The aim of this
work was to characterize nuclear changes observed in metastatic cell clones
issued in vitro from the same parental cell population The nuclear phenotypes of
6 cell sublines isolated from a rat rhabdomyosarcoma cell line and differing in
their metastatic ability were evaluated by image cytometry on Feulgen-stained
preparations. Densitometric [5], geometric [3] and textural [9] features were
computed from each nuclear image. For each cell subline, a metastatic score,
ranging from 0 to 10, was calculated on the basis of in vivo invasivity data, by
measuring the number of pulmonary metastases observed after s.c. graft of tumor
cells in rats. Data obtained were compared to karyotype, growth characteristics,
and oncogene expressions of cell lines. The nuclear DNA content, the chromosome
numbers, the cell sublines doubling times, and the distribution of cells within
the cell cycle appear unrelated with this score. On the contrary, increase in
metastatic ability is accompanied by changes in chromatin pattern as assessed by
textural features. Progressive increase in chromatin condensation can be observed
in cell sublines with increasing metastatic score. These results were confirmed
by an unsupervised multivariate partitioning of rhabdomyosarcoma cells which
identified two separate subsets whose distributions within the analyzed cell
lines correlate with their metastatic ability. These data suggest that, in rat
rhabdomyosarcoma cell sublines, metastatic ability could be associated with
nuclear morphological changes at the level of chromatin texture.
PMID- 11007438
TI - Evaluation of tumor heterogeneity of prostate carcinoma by flow- and image DNA
cytometry and histopathological grading.
AB - BACKGROUND: Heterogeneity of prostate carcinoma is one of the reasons for
pretreatment underestimation of tumor aggressiveness. We studied tumor
heterogeneity and the probability of finding the highest tumor grade and DNA
aneuploidy with relation to the number of biopsies. MATERIAL AND METHODS:
Specimens simulating core biopsies from five randomly selected tumor areas from
each of 16 Bocking's grade II and 23 grade III prostate carcinomas were analyzed
for tumor grade and DNA ploidy by flow- and fluorescence image cytometry (FCM,
FICM). Cell cycle composition was measured by FCM. RESULTS: By determination of
ploidy and cell cycle composition, morphologically defined tumors can further be
subdivided. Heterogeneity of tumor grade and DNA ploidy (FCM) was 54% and 50%.
Coexistence of diploid tumor cells in aneuploid specimens represents another form
of tumor heterogeneity. The proportion of diploid tumor cells decreased
significantly with tumor grade and with increase in the fraction of proliferating
cell of the aneuploid tumor part. The probability of estimating the highest tumor
grade or aneuploidy increased from 40% for one biopsy to 95% for 5 biopsies
studied. By combining the tumor grade with DNA ploidy, the probability of
detecting a highly aggressive tumor increased from 40% to 70% and 90% for one and
two biopsies, respectively. CONCLUSION: Specimens of the size of core biopsies
can be used for evaluation of DNA ploidy and cell cycle composition.
Underestimation of aggressiveness of prostate carcinoma due to tumor
heterogeneity is minimized by simultaneous study of the tumor grade and DNA
ploidy more than by increasing the number of biopsies. The biological
significance of coexistent diploid tumor cell in aneuploid lesions remains to be
evaluated.
PMID- 11007440
TI - EEG bands during wakefulness, slow-wave and paradoxical sleep as a result of
principal component analysis in man.
AB - Human electroencephalogram (EEG) has been divided in bands established by visual
inspection that frequently do not correspond with EEG generators nor with
functional meaning of EEG rhythms. Power spectra from wakefulness, stage 2, stage
4 and paradoxical sleep of 8 young adults were submitted to Principal Component
Analyses to investigate which frequencies covaried together. Two identical
eigenvectors were identified for stage 2 and stage 4: 1 to 8 Hz and 5 to 15 Hz
(87.95 and 84.62 % of the total variance respectively). Two eigenvectors were
extracted for PS: 1 to 9 Hz and 10 to 15 Hz (81.62% of the total variance). Three
eigenvectors were obtained for W: with frequencies between 1 to 7 Hz, 7 to 11 Hz,
and 12 to 15 Hz (78.32% of the total variance). Power for all frequencies showed
significant differences among vigilance states. These results indicate that slow
wave activity can oscillate at higher frequencies, up to 8 Hz, and that spindle
oscillations have a wider range down to 5 Hz. No theta band was independently
identified, suggesting either that delta and theta oscillations are two rhythms
under the same global influence, or that the traditional division of theta band
in the human cortical EEG is artificial. Alpha as a band was identified only
during wakefulness. Principal component analysis upon spectral densities
extracted broad bands different for each vigilance state and from traditional
bands, consistent with functional significance of EEG and with frequencies of
generators of rhythmic activity obtained in cellular studies in animals.
PMID- 11007439
TI - Development of disturbing dreams during adolescence and their relation to anxiety
symptoms.
AB - STUDY OBJECTIVES: This work assesses the prevalence and development of disturbing
dreams among adolescents and the association of these dreams with anxiety.
DESIGN: Sex differences in prevalence were analyzed with chi-square analyses.
Changes over time were assessed with Wilcoxon tests and cross-tabulation tables.
Associations with anxiety and DSM-III-R symptoms were assessed with ANOVA
designs. SETTING: N/A. PARTICIPANTS: A total of 610 boys and girls rated their
recall of disturbing and normal dreams at both 13 and 16 years of age. Subgroups
of subjects were evaluated for anxiety symptoms at age 13 and for DSM-III-R
symptoms of separation anxiety (SA), overanxious disorder (OD) and generalized
anxiety disorder (GAD) at age 16. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS:
The recall of disturbing dreams was more prevalent for girls than for boys at
both ages, and increased over time for girls while it decreased for boys. The
recall of normal dreams was also more prevalent for girls at both ages, but this
difference could not fully account for the difference in recall of disturbing
dreams. Normal dream recall increased from age 13 to 16 for both sexes. The
frequent occurrence of disturbing dreams was associated with anxiety at age 13
and with GAD, SA and OD symptoms at age 16 for both sexes. Evidence of more
numerous OD symptoms for girls with frequent disturbing dreams suggests that this
form of anxiety may partially account for the observed sex difference in
disturbing dream prevalence. CONCLUSIONS: The findings highlight a prevalence of
disturbing dreams that is especially marked for adolescent girls. Unlike previous
cross-sectional studies, which have found the same sex difference, this
longitudinal design also calls attention to within-subjects changes in disturbing
dream recall. The results also confirm that the frequent recall of disturbing
dreams is associated with pathological symptoms of trait anxiety-apparently even
as young as 13 years of age. Further study of disturbing dreams may contribute to
understanding of associated pathophysiological factors which, too, vary by sex
(e.g., PTSD, insomnia, depression).
PMID- 11007441
TI - Spectral features of EEG alpha activity in human REM sleep: two variants with
different functional roles?
AB - Evidence suggests that an important contribution of spectral power in the alpha
range is characteristic of human REM sleep. This contribution is, in part, due to
the appearance of well-defined bursts of alpha activity not associated with
arousals during both tonic and phasic REM fragments. The present study aims at
determining if the REM-alpha bursts constitute a different alpha variant from the
REM background alpha activity. Since previous findings showed a selective
suppression of background alpha activity over occipital regions during phasic REM
fragments and, on the other hand, the density of alpha bursts seem to be
independent of the presence or absence of rapid eye movements, one expects to
find the same spectral power contribution of alpha bursts in tonic and phasic REM
fragments. The results indicated that REM-alpha bursts showed a similar power
contribution and topographic distribution (maximum energy over occipital regions)
both in tonic and phasic REM fragments. This suggests that two variants of alpha
activity with different functional roles are present during the human REM sleep:
i) background alpha activity, modulated over occipital regions by the presence of
rapid eye movements, which may be an electrophysiological correlate of the visual
dream contents; and ii) REM-alpha bursts, independent of the presence of rapid
eye movements, which could be facilitating the connection between the dreaming
brain and the external world, working as a micro-arousal in this brain state.
PMID- 11007442
TI - Dynamics of slow-wave activity during the NREM sleep of sleepwalkers and control
subjects.
AB - STUDY OBJECTIVE: To compare the number and distribution of awakenings from slow
wave sleep (SWS) and both the power and dynamics of EEG slow-wave activity (SWA)
in sleepwalkers and controls. Somnambulism is considered to be a disorder of
arousal from NREM sleep and related to anomalous SWS and SWA. Power spectral
analyses have never been used to quantify patients' SWA across sleep cycles.
DESIGN: N/A SETTING: N/A PATIENTS: A polysomnographic study was performed on 15
adult sleepwalkers and 15 age- and sex-matched controls. INTERVENTIONS: N/A
MEASUREMENTS & RESULTS: Sleepwalkers had a significantly greater number of
awakenings from SWS than did control subjects. Controls showed a greater decrease
in SWA across NREM cycles. Sleepwalkers had a significantly lower level of SWA
during the first NREM period, where most awakenings take place. CONCLUSION:
Sleepwalkers appear to suffer from an abnormality in the neural mechanisms
responsible for the regulation of SWS.
PMID- 11007443
TI - Non-Invasive detection of respiratory effort-related arousals (REras) by a nasal
cannula/pressure transducer system.
AB - STUDY OBJECTIVES: The published AASM guidelines approve use of a nasal
cannula/pressure transducer to detect apneas/hypopneas, but require esophageal
manometry for Respiratory Effort-Related Arousals (RERAs). However, esophageal
manometry may be poorly tolerated by many subjects. We have shown that the shape
of the inspiratory flow signal from a nasal cannula identifies flow limitation
and elevated upper-airway resistance. This study tests the hypothesis that
detection of flow limitation events using the nasal cannula provides a non
invasive means to identify RERAs. DESIGN: N/A. SETTING: N/A. PATIENTS: 10
UARS/OSAS and 5 normal subjects INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All
subjects underwent full NPSG. Two scorers identified events from the nasal
cannula signal as apneas, hypopneas, and flow limitation events. Two additional
scorers identified events from esophageal manometry. Arousals were scored in a
separate pass. Interscorer reliability and intersignal agreement were assessed
both without and with regard to arousal. The total number of respiratory events
identified by the two scorers of the nasal cannula was similar with an Intraclass
Correlation (ICC) =0.96, and was essentially identical to the agreement for the
two scorers of esophageal manometry (ICC=0.96). There was good agreement between
the number of events detected by the two techniques with a slight bias towards
the nasal cannula (4.5 events/hr). There was no statistically significant
difference (bias 0.9/hr, 95%CI -0.3-2.0) between the number of nasal cannula flow
limitation events terminated by arousal and manometry events terminated by
arousal (RERAs). CONCLUSION: The nasal cannula/pressure transducer provides a non
invasive reproducible detector of all events in sleep disordered breathing; in
particular, it detects the same events as esophageal manometry (RERAs).
PMID- 11007445
TI - Supine cephalometric study on sleep-related changes in upper-airway structures in
normal subjects.
AB - The purpose of this study was to examine sleep-related changes in the upper
airway and surrounding structures including the mandible, hyoid bone, and
cervical vertebra in normal subjects using lateral cephalograms in the supine
position. Eleven male and nine female healthy adults participated in this study.
Supine cephalograms were taken at end-expiration during wakefulness and in stage
1-2 non-rapid-eye-movement (NREM) sleep judged from the electroencephalogram and
respiratory monitoring. A paired t-test was used to compare differences between
the values measured during wakefulness and sleep. A significant increase in the
amount of jaw opening was observed during sleep. The anteroposterior width of the
upper airway was significantly decreased during sleep. The distances between the
hyoid bone and the mandibular symphysis and between the cervical vertebra and the
hyoid bone were significantly decreased during sleep. Consequently, the distance
between the cervical vertebra and the mandibular symphysis was significantly
decreased. These results suggest that the upper-airway dimension is significantly
decreased and relatively small structural changes are induced during sleep in
normal subjects.
PMID- 11007444
TI - Erectile dysfunction in men with obstructive sleep apnea: an early sign of nerve
involvement.
AB - Erectile dysfunction (ED) is common in men with obstructive sleep apnea (OSAS)
but no completely convincing hypotheses about the underlying pathogenic
mechanisms have been published in the literature. The aims of the present study
were to assess the presence of ED in a group of OSAS patients without daytime
respiratory failure and to determine whether this dysfunction was related to
peripheral nerve involvement. Evaluation of the bulbocavernosus reflex (BCR) and
the somato-sensory evoked potentials of pudendal nerve (PSEPs), the most widely
established method of documenting pudendal neuropathies as being the cause of
impotence, was performed in 25 patients. Data on BCR were compared with those of
25 healthy males volunteers matched for age. BCR was altered in 17 patients: in 6
it was elicited while in 11 it had a prolonged latency and reduced amplitude.
Patients with altered BCR presented an higher AHI, an higher percentage of sleep
time spent with SaO2 <90% (TST90) and a lower daytime PaO2. Six patient had
clinically silent neurophysiological signs of mild polyneuropathy. The degree of
OSAS and gas exchange alteration was more severe in patients with polyneuropathy
than in those with isolated BCR alteration. ED is a common finding in OSAS
patients and this alteration seems to be related to a nerve dysfunction. The
development of nerve dysfunction is associated with a more severe degree of OSAS
and nocturnal hypoxia.
PMID- 11007447
TI - Voluntary oculomotor performance upon awakening after total sleep deprivation.
AB - The potential impact of sleep inertia on measures of voluntary oculomotor control
have been surprisingly neglected. The present study examined the effects of 40
hours of sleep deprivation on saccadic (SAC) and smooth pursuit (SP) performance,
attentional/visual search performance (Letter Cancellation Task, LCT) and
subjective sleepiness (Sleepiness Visual Analog Scale, SVAS) recorded immediately
after awakening. Standard polysomnography of nine normal subjects was recorded
for 3 nights (1 adaptation, AD; 1 baseline, BSL; 1 recovery, REC); BSL and REC
were separated by a period of 40 h of continuous wakefulness, during which
subjects were tested every two hours. Within 30 s of each morning awakening, a
test battery (SAC, SP, LCT, SVAS) was administered to subjects in bed. For data
analysis, mean performance obtained during the day preceding the sleep
deprivation night was considered as "Diurnal Baseline" and compared to
performance upon awakening from nocturnal sleep. As a consequence of sleep
deprivation, SWS percentage was doubled during REC. Saccade latency increased and
velocity decreased significantly upon awakening from REC as compared to the other
three conditions (Diurnal baseline, AD awakening, BSL awakening); accuracy was
unaffected. As regards SP, phase did not show any impairment upon awakening,
while velocity gain upon awakening from REC was significantly lower as compared
to the other conditions. Finally, number of hits on LCT upon awakening from REC
was significantly lower and subjective sleepiness higher as compared to Diurnal
Baseline. It is concluded that 40 h of sleep deprivation significantly impaired
performance to SAC and SP tasks recorded upon awakening from recovery sleep. This
performance worsening is limited to the measures of speed, while both SAC
accuracy and SP phase do not show a significant decrease upon awakening. Since
saccadic velocity has recently been found to negatively correlate with simulator
vehicle crash rates, it is suggested that the adverse effects of sleep
deprivation on sleep inertia magnitude should be avoided by any personnel who may
have to perform critical tasks involving high oculomotor control immediately
after awakening.
PMID- 11007446
TI - Effects of sleep loss on waking actigraphy.
AB - STUDY OBJECTIVES: To assess the effect of sleep loss and the effect of a sedating
drug on waking actigraphy DESIGN: N/A SETTING: N/A PARTICIPANTS: Seventeen
healthy volunteers, aged 19-35 yrs INTERVENTIONS: Four night-day treatments
presented in a Latin Square Design: placebo-8 hr time-in-bed (TIB), placebo-4 hr
TIB, placebo-0 hr TIB, and diphenhydramine 50 mg-8 hr TIB. MEASUREMENTS AND
RESULTS: After the appropriate TIB, medication was administered at 09:00 hr, the
Multiple Sleep Latency Test at 09:30, 11:30, 13:30, 15:30, and 17:30 hr, and a 45
min performance battery at 10:30, 14:30, and 16:30 hr. Each day the volunteers
wore actigraphs from 0700-1800 hrs. Decreasing TIB was associated with decreased
daily mean sleep latency on the MSLT with 4 and 0 hrs differing from 8 hrs and
each other. Daytime activity also was reduced by the reduced prior TIB. Increased
inactivity relative to the 8 hr TIB developed between the 4 hr and 0 hr TIBs,
with 4 hrs differing from 0 hrs, but not 8 hrs. Diphenhydramine 50 mg reduced
mean daily sleep latency and increased percent inactive time relative to placebo.
On the MSLT diphenhydramine was intermediate to 4 hr and 0 hr TIB and on
actigraphy it was similar to 0 hr TIB. CONCLUSIONS: The difference in the effect
of diphenhydramine on these actigraphy and MSLT may reflect the different
sensitivities of the measures.
PMID- 11007448
TI - Maintenance of alertness and performance by a brief nap after lunch under prior
sleep deficit.
AB - We examined the effects of a 15-min nap after lunch on subsequent alertness,
performance, and autonomic function following a short sleep the preceding night.
Subjects were 12 healthy students who had slept for only 4 hours the night before
being tested. They experienced both nap and no-nap conditions in a
counterbalanced order, at least a week apart. The nap condition included a 15-min
nap opportunity (12:30-12:45) in bed with polygraphic monitoring. We measured the
P300 event-related potential, subjective sleepiness (Visual Analog Scale), and
electrocardiogram (ECG) at 10:00, 13:15, and 16:15, and task performance (logical
reasoning and digit span) at 10:00, 11:30, 13:15, 14:45, 16:15, and 17:45. Mean
home sleep measured by actigraphy was 3.5 hours under both conditions. At 13:15,
the P300 latency after the nap was significantly shorter than after no nap, but
its amplitude was not affected by napping. Subjective sleepiness at 13:15 and
14:45 was significantly lower, and accuracy of logical reasoning at 13:15 was
significantly higher after the nap than after no nap. No other performance
measures or the ECG R-R interval variability parameters differed significantly
between the nap and no-nap conditions. Mean total sleep time during the nap was
10.2 min, and no stage 3 and 4 sleep was observed. The above results suggest that
under prior sleep deficit, a 15-min nap during post-lunch rest maintains
subsequent alertness and performance, particularly in the mid-afternoon.
PMID- 11007449
TI - Automatic auditory information processing in sleep.
AB - STUDY OBJECTIVES: The mismatch negativity (MMN) component of the event-related
potentials reflects the automatic detection of sound change. Only a few
researchers have investigated the MMN elicitation during sleep in adult human and
some of them reported that MMN amplitude was decreased in sleep compared to in
waking. However, it is not clear that the decrease of MMN amplitude was due to
increased drowsiness or long-term response decrement. Two experiments were
conducted to clarify whether or not the MMN was elicited in each sleep stage. We
presented auditory stimuli to subjects continuously from waking until sleep state
(Experiment 1). Using the same experimental condition, we examined whether or not
MMN amplitude was influenced by long-term stimulus presentation (80min.) and by
vigilance level (Experiment 2). DESIGN: N/A SETTING: N/A PARTICIPANTS: N/A
INTERVENTIONS: N/A MEASUREMENTS & RESULTS: Experiment 1: MMN was obtained in both
drowsiness and REM sleep. MMN was significantly smaller in amplitude and shorter
in latency in the both stages than in the waking state. However, MMN was not
found in another sleep stage. Experiment 2: Amplitudes were no different among 0
20 min., 20-40 min., 60-80 min. But it was decreased in 40-60 min. and power
value of alpha-wave was decreased in 40-60 min. CONCLUSIONS: To obtain the
reliable data, by using the automatic spectral analysis, we confirmed that MMN
was elicited in REM sleep. MMN was not influenced by long-term stimulation. The
result suggested that auditory stimuli could be processed in the pre-attentive
sensory memory even in REM sleep.
PMID- 11007450
TI - A possible role for nitric oxide at the sleep/wake interface.
AB - Cholinergic neurotransmission is known to have important arousal/activating
functions. The neurons responsible for those actions also release the atypical
neuromodulator nitric oxide (NO), which has been shown in previous studies to be
involved in the modulation of sleep/wake states. The present investigation, using
an animal model (anesthetized cat) tests the hypothesis that NO cooperates with
ACh in controlling rhythmic neuronal activity, which may play a role in
sleep/wake transition. We have used extracellular singleunit recording of neurons
in the dorsal thalamus and visual cortex with simultaneous iontophoretic
application of drugs acting upon the NO system: the nitric oxide synthase (NOS)
inhibitor NG-nitro-L-arginine (L-NOArg), NO donors, and 8-bromo-cGMP (which
mimics the action of NO). Local inhibition of NOS significantly reduced the
activity of recorded cells in both thalamus and visual cortex. The opposite
effect was achieved with NO donors application. In cortex, ejection of 8-bromo
cGMP or the NO donor diethylamine-nitric oxide (DEA-NO) increased cell firing.
Furthermore, the rhythmic firing pattern present in these cortical neurons was
disrupted. Taken together, these findings suggest that the NO system collaborates
with cholinergic neurotransmission. This collaboration might be involved in the
control of different patterns of electrogenic activity during various states of
the sleep-wake cycle, via the ability of the NO system to modify rhythmic
activity of neurons.
PMID- 11007451
TI - Aberrant regulation and function of wild-type p53 in radioresistant melanoma
cells.
AB - Sporadic human tumors and the hereditary cancer predisposition syndrome Li
Fraumeni are frequently associated with mutations in the p53 tumor suppressor
gene that compromise its ability to function as a DNA damage checkpoint. A subset
of Li-Fraumeni patients with wild-type p53 alleles have mutations in chk2/hcds1,
one of the genes signaling the presence of DNA damage to the p53 protein. This
suggests that p53 may be kept inactive in human cancer by mutations targeting DNA
damage signaling pathways. Melanoma cells are highly radioresistant, yet they
express wild-type p53 protein, raising the possibility of defects in the pathways
that activate p53 in response to DNA damage. We have described a chk2/hcds1
independent DNA damage signaling pathway that targets Ser-376 within the COOH
terminus of p53 for dephosphorylation and leads to increased p53 functional
activity. We now report that in several human melanoma cell lines that express
wild-type p53, the phosphorylation state of Ser-376 was not regulated by DNA
damage. In these cell lines, neither the endogenous wild-type p53 protein nor
high levels of ectopic wild-type p53 led to cell cycle arrest or apoptosis. Thus,
defective activation of p53 in response to DNA damage may underlie the
radioresistance of human melanoma cells.
PMID- 11007452
TI - p202 levels are negatively regulated by serum growth factors.
AB - p202 is an IFN-inducible phosphoprotein (Mr 52,000) whose expression in
transfected cells retards proliferation. Interestingly, the reduced levels of
p202 in fibroblasts (in consequence of the expression of antisense to 202 RNA),
under reduced serum conditions, increase the susceptibility of cells to
apoptosis. To identify the functional role of p202 in cell growth regulation, we
tested whether serum growth factor levels in the culture medium affect p202
levels. Here we report that, under reduced serum conditions, the p202 levels were
increased in fibroblasts, and the increase was seen at both the mRNA and protein
levels. Moreover, an increase in p202 levels was correlated with cell growth
arrest in the G1 phase of the cell cycle. Interestingly, the presence of platelet
derived growth factor AB, basic fibroblast growth factor, or transforming growth
factor beta1 in the culture medium abrogated the increase in p202 levels seen
under reduced serum conditions. We found that the increase in p202 levels was
accompanied by an increase in JunD/activation protein 1(AP-1) levels, and
transfection of a JunD-encoding plasmid along with a reporter plasmid in which
transcription of the reporter gene (luciferase) was driven by the 5'-regulatory
region of the 202 gene resulted in an increase in the activity of luciferase.
Additionally, stable overexpression of JunD in cells, under reduced serum
conditions, also resulted in an increase in p202 levels. Interestingly, one of
the AP-1-like DNA-binding sequences present in the 5'-regulatory region of the
202 gene could selectively bind to the JunD/AP-1 transcription factor. Taken
together, our observations reported herein suggest that in fibroblasts, under
reduced serum conditions, the increased levels of JunD/AP-1 contribute to the
transcriptional up-regulation of p202 levels, which may be important for the
regulation of apoptosis.
PMID- 11007453
TI - Inhibition of progesterone-induced Xenopus oocyte maturation by Nm23.
AB - The Nm23 protein has been implicated in a wide variety of biological processes,
including suppression of metastasis, phytochrome responses in plants, and
regulation of differentiation. Here we examine whether Nm23 is involved in
Xenopus laevis oocyte maturation. We found that Nm23 is present in oocytes,
indicating that it has the potential to be a regulator of maturation.
Furthermore, modest overexpression of Nm23 inhibited progesterone-induced oocyte
maturation. This maturation-inhibitory activity was shared by both the acidic
Nm23-H1 isoform and the basic Nm23-H2 isoform and by Nm23 mutants that lack
nucleoside diphosphate kinase activity (Nm23-H1 H118F and Nm23-H2 H118F).
Expression of Nm23 proteins delayed the accumulation of Mos and the activation of
p42 mitogen-activated protein kinase (MAPK) in progesterone-treated oocytes but
had no discernible effect on Mos-induced p42 MAPK activation. Therefore, Nm23
appears to act upstream of the Mos/mitogen-activated protein/extracellular signal
regulated kinase kinase/p42 MAPK cascade. These findings suggest a novel
biological role for Nm23.
PMID- 11007454
TI - Protein kinase C inhibitor and irradiation-induced apoptosis: relevance of the
cytochrome c-mediated caspase-9 death pathway.
AB - Caspases are a family of cysteine proteases that constitute the apoptotic cell
death machinery. We report the importance of the cytochrome c-mediated caspase-9
death pathway for radiosensitization by the protein kinase C (PKC) inhibitors
staurosporine (STP) and PKC-412. In our genetically defined tumor cells,
treatment with low doses of STP or the conventional PKC-specific inhibitor PKC
412 in combination with irradiation (5 Gy) potently reduced viability, enhanced
mitochondrial cytochrome c release into the cytosol, and specifically stimulated
the initiator caspase-9. Whereas treatment with each agent alone had a minimal
effect, combined treatment resulted in enhanced caspase-3 activation. This was
prevented by broad-range and specific caspase-9 inhibitors and absent in caspase
9-deficient cells. The tumor suppressor p53 was required for apoptosis induction
by combined treatment but was dispensable for dose-dependent STP-induced caspase
activation. These results demonstrate the requirement for an intact caspase-9
pathway for apoptosis-based radiosensitization by PKC inhibitors and show that
STP induces apoptosis independent of p53.
PMID- 11007455
TI - K562 cells resistant to phorbol 12-myristate 13-acetate-induced growth arrest:
dissociation of mitogen-activated protein kinase activation and Egr-1 expression
from megakaryocyte differentiation.
AB - The K562 cell line undergoes megakaryocytic differentiation in response to
phorbol 12-myristate 13-acetate (PMA) stimulation. This event correlates with
mitogen-activated protein kinase activation, cell cycle arrest, and expression of
the Egr-1 transcription factor. We have isolated K562 cells that are resistant to
the growth-inhibitory action of PMA. Molecular characterization demonstrates that
PMA resistance is downstream from PMA-induced activation of the mitogen-activated
protein kinase pathway. Although the levels of Egr-1 expression and cyclic AMP
responsive element-binding protein phosphorylation are comparable in wild-type
and PMA-resistant clones in response to PMA, the expression of megakaryocytic
cell surface marker CD41 is detected only in the wild-type cells. The lack of
differentiation of the PMA-resistant clones correlates with a failure of the PMA
treated cells to induce dephosphorylation and down-regulation of the
retinoblastoma protein. These cells may provide a useful model system to
distinguish those events that are connected to cell cycle arrest from those
involved in the differentiation program initiated by PMA.
PMID- 11007456
TI - Internal exposure from the ingestion of foods contaminated by 137Cs after the
Chernobyl accident--report 2. Ingestion doses of the rural population of Ukraine
up to 12 y after the accident (1986-1997).
AB - Doses from the ingestion of 134Cs and 137Cs during 12 y following the Chernobyl
accident have been estimated for approximately 3 million persons living in rural
areas of the Zhitomir, Rivne, and Kyiv Oblasts of northern Ukraine. This
assessment is based upon an extensive monitoring campaign that provided
measurements of 137Cs in more than 120,000 samples of milk and in more than
100,000 persons; such measurements were made in approximately 4,500 locations.
Two approaches were used for the dose assessment. In the first approach a so
called reference dose is estimated for each settlement on the basis of measured
137Cs concentration in milk, determination of the milk equivalent of diet, and
consumption rates; a further assumption is that a high fraction of the food
consumed is produced locally. The reference dose is used as the official dose
estimate, which is the basis for any decision on possible financial compensation
and economic privileges. In a second step, the so-called real age-dependent dose
is estimated from the results of whole body counter measurements and the kinetics
of radiocesium in the human body. Real doses above 0.5, 5, and 50 mSv were
received by about 40%, 10%, and 0.2%, respectively, of the considered population.
With the exception of 1986, for which the monitoring results were limited, the
real individual doses derived from whole-body counting are consistently lower
than the reference doses. However, this difference declined from a factor of 3-4
in 1987-1989 to a factor of approximately 1.5 in the mid 1990's. The difference
between reference and real doses is attributed to the effectiveness of
countermeasures implemented after the accident. The effectiveness of these
countermeasures decreased with time due to increasing economic problems in
Ukraine. The collective reference and real doses of the rural population due to
the intake of 134Cs and 137Cs are estimated to be 13,300 and 5,300 person-Sv,
respectively. Thus, about 8,000 person-Sv is estimated to have been averted by
countermeasures.
PMID- 11007457
TI - Accelerator mass spectrometry of 63Ni at the Munich Tandem Laboratory for
estimating fast neutron fluences from the Hiroshima atomic bomb.
AB - After the release of the present dosimetry system DS86 in 1987, measurements have
shown that DS86 may substantially underestimate thermal neutron fluences at large
distances (>1,000 m) from the hypocenter in Hiroshima. This discrepancy casts
doubts on the DS86 neutron source term and, consequently, the survivors'
estimated neutron doses. However, the doses were caused mainly by fast neutrons.
To determine retrospectively fast neutron fluences in Hiroshima, the reaction
63Cu(n, p)63Ni can be used, if adequate copper samples can be found. Measuring
63Ni (half life 100 y) in Hiroshima samples requires a very sensitive technique,
such as accelerator mass spectrometry (AMS), because of the relatively small
amounts of 63Ni expected (approximately 10(5)-10(6) atoms per gram of copper).
Experiments performed at Lawrence Livermore National Laboratory have demonstrated
in 1996 that AMS can be used to measure 63Ni in Hiroshima copper samples.
Subsequently, a collaboration was established with the Technical University of
Munich in view of its potential to perform more sensitive measurements of 63Ni
than the Livermore facility and in the interest of interlaboratory validation.
This paper presents the progress made at the Munich facility in the measurement
of 63Ni by AMS. The Munich accelerator mass spectrometry facility is a
combination of a high energy tandem accelerator and a detection system featuring
a gas-filled magnet. It is designed for high sensitivity measurements of long
lived radioisotopes. Optimization of the ion source setup has further improved
the sensitivity for 63Ni by reducing the background level of the 63Cu isobar
interference by about two orders of magnitude. Current background levels
correspond to a ratio of 63Ni/Ni<2x10(-14) and suggest that, with adequate copper
samples, the assessment of fast neutron fluences in Hiroshima and Nagasaki is
possible for ground distances of up to 1500 m, and--under favorable conditions-
even beyond. To demonstrate this capability, we have measured successfully 6Ni/Ni
ratios as low as (3.5 +/- 0.6) x 10(-13). The latter are, based on DS86,
representative of a ratio expected from a typical Hiroshima copper sample at
about 1,300-m ground range.
PMID- 11007458
TI - Radon progeny exposure and lung cancer risk among non-smoking uranium miners.
AB - Studies of miners provide the basis for public health efforts to reduce
residential radon progeny exposure. Because the preponderance of households do
not have members who smoke indoors, studies of non-smoking miners contribute
essential data for risk assessments for residential radon progeny exposure. We
studied a cohort of 2,209 never-smokers who were underground uranium miners
employed in the western U.S. from 1956 to the early 1990's and who participated
in a screening program for lung cancer conducted by Saccomanno and colleagues.
After determining the vital status and cause of death in the cohort, we conducted
a nested case-control study of 55 lung cancer deaths in males and 3 age-matched
controls for each case. The relative risk of lung cancer was 29.2 (95% CI 5.1,
167.2) for miners with greater than 1,450 WLM compared with those exposed to less
than 80 WLM. Temporal factors affected risk, including average dose rate, which
was inversely associated with lung cancer risk, and the length of time since last
exposure, which was directly associated with decreased risk. As in studies of non
smokers and smokers combined, the exposure response relationship in never-smokers
was consistent with a decreased slope at higher WLM, which resulted, in part,
from an inverse dose rate effect.
PMID- 11007459
TI - Restricting exposure to pulsed and broadband magnetic fields.
AB - A general procedure is described for application of the new ICNIRP exposure
guidelines to pulsed and broadband magnetic fields below 100 kHz. The procedure
involves weighting of the spectral components with a function that takes into
account the basic restrictions and reference levels. A simple first-order RC
response or its piecewise linear equivalent is proposed for the weighting
function. The weighting can be performed either on the Fourier transformed sample
of the measured signal or in real time by processing the signal with an analog or
digital filter circuit. The cut-off frequency of the filter is 820 Hz. The
occupational exposure criteria are exceeded when the weighted peak magnetic flux
density exceeds 43 microT or equivalently the weighted peak dB/dt exceeds 0.22 T
s(-1). The maximal peak exposures allowed by the proposed approach are compared
with the stimulation thresholds computed with a stimulation model. The results
strongly suggest that the safety margin to the stimulation is greater for non
sinusoidal than for sinusoidal waveforms, and at low frequencies it is higher
than at high frequencies. The increase of the low-frequency safety margin is
desirable to avoid magnetophosphenes and possible CNS effects that may occur
below the level predicted by the classical nerve models. Measurement techniques
and examples of measured magnetic fields are presented. Particularly high
exposures were measured inside MRI equipment and anti-theft gates.
PMID- 11007460
TI - Theoretical study of the relation between radon and its long-lived progeny in a
room.
AB - We present a theoretical study of the complex relation between radon and its long
lived progeny implanted in glass surfaces. The well known (extended) Jacobi room
model, which is normally used to describe radon and its progeny in a room, was
transformed into a two-parameter model revealing a linear correlation between
long term radon exposure and surface activity due to implanted radon decay
products. Furthermore, this new approach made integration into a Monte Carlo
simulation possible so that the large variation of different room model
parameters could be taken into account. This allowed the calculation of a
probability distribution for radon exposure from the measurement of the implanted
210Po activity. The availability of a 95% confidence interval for the radon
exposure is valuable in the application of retrospective radon assessment in
epidemiological studies.
PMID- 11007461
TI - In situ hot spot measurements with HPGe detector 0.1 M above ground.
AB - The objective of this study was to examine the feasibility of an accurate in situ
measurement of radioactive hot spots by a HPGe detector located at a height of
0.1 m above the surface, thus sparing the awkward use of a heavy collimator
required at the standard 1 m height. Radioactivity concentrations of primordial
naturally occurring 40K, 232Th, 238U and of anthropogenic 137Cs in a sand plot
were measured in situ at the two heights. Independently, six fractions of a soil
profile collected in the site were measured in the laboratory. Good agreement was
found between the results of the two geometries and the soil samples. Good
agreement between measured and predicted radioactivity concentration values was
obtained for hot spots simulated by uniform planar sources of 40K, 60Co and 137Cs
having a circular pattern 0.5 m in diameter. The study shows that an in situ
measurement without a collimator but close to a hot spot can provide a reliable
result.
PMID- 11007462
TI - Using measured 30-150 kVp polychromatic tungsten x-ray spectra to determine ion
chamber calibration factors, Nx (Gy C(-1)).
AB - Two methods for determining ion chamber calibration factors (Nx) are presented
for polychromatic tungsten x-ray beams whose spectra differ from beams with known
Nx. Both methods take advantage of known x-ray fluence and kerma spectral
distributions. In the first method, the x-ray tube potential is unchanged and
spectra of differing filtration are measured. A primary standard ion chamber with
known Nx for one beam is used to calculate the x-ray fluence spectrum of a second
beam. Accurate air energy absorption coefficients are applied to the x-ray
fluence spectra of the second beam to calculate actual air kerma and Nx. In the
second method, two beams of differing tube potential and filtration with known Nx
are used to bracket a beam of unknown Nx. A heuristically derived Nx
interpolation scheme based on spectral characteristics of all three beams is
described. Both methods are validated. Both methods improve accuracy over the
current half value layer Nx estimating technique.
PMID- 11007463
TI - On the application of a radiation weighting factor for alpha particles in
protection of non-human biota.
AB - Radiation protection standards for non-human biota have been expressed in terms
of absorbed dose. In calculating dose to biota, some investigators have modified
the absorbed dose due to alpha particles by a factor of 20, based on the
radiation weighting factor used in protection of humans, to account for the
greater effectiveness of these radiations in producing biological damage.
However, this value is intended to apply to stochastic health effects, primarily
cancers, whereas deterministic effects have been the primary concern in
protection of biota. Based on an analysis by the International Commission on
Radiological Protection, the deterministic radiation weighting factor for alpha
particles appears to lie in the range of about 5-10. Given the potential
importance of this weighting factor in determining allowable levels of alpha
emitting radionuclides in the environment, regulatory authorities must be
impressed with the need to develop an appropriate value for use in protection of
biota. There also is a need to express doses and dose limits for biota in terms
of a quantity other than absorbed dose and to develop an appropriate name for the
biologically significant dose to biota.
PMID- 11007464
TI - The LNT-controversy and the concept of "controllable dose".
AB - There is no firm scientific information on the potential health effects, such as
increased cancer rates, due to low doses of ionizing radiation. In view of this
uncertainty ICRP has adopted as a prudent default option the linear no-threshold
(LNT) assumption and has used it to derive nominal risk coefficients. Subsequent
steps, such as the comparison of putative fatality rates in radiation workers
with observed accident rates in other professions, have given the risk estimates
a false appearance of scientific fact. This has encouraged meaningless
computations of radiation-induced fatalities in large populations and has caused
a trend to measure dose limits for the public not against the magnitude of the
natural radiation exposure and its geographic variations, but against the
numerical risk estimates. In reaction to this development, opposing claims are
being made of a threshold in dose for deleterious health effects in humans. In
view of the growing polarization, ICRP is now exploring a new concept
"controllable dose" that aims to abandon the quantity collective dose,
emphasizing, instead, individual dose and, in particular, the control of the
maximum individual dose from single sources. Essential features of the new
proposal are here examined, and it is concluded that the control of individual
dose will still have to be accompanied by the avoidance of unnecessary exposures
of large populations, even if their magnitude lies below that acceptable to the
individual. If a reasonable cut-off at trivial doses is made, the collective dose
can remain useful. Misapplications of collective dose are not the deeper cause of
the current controversy; the actual root is the misrepresentation of the LNT
assumption as a scientific fact and the amplification of this confusion by loose
terminology. If over-interpretation and distortion are avoided, the current
system of radiation protection is workable and essentially sound, and there is no
need for a fruitless LNT-controversy. The new concept of controllable dose
promises simplifications and improvements, but any major change of principles
needs to be carefully considered in a broad discussion that ICRP is presently
seeking.
PMID- 11007465
TI - Internal dosimetry of plutonium using the late urinary excretion.
AB - An attempt has been made to standardize the methodology of internal dose
computation from the late urinary excretion data. The methodology was selected
keeping in mind the most recent ICRP publications and the results of internal
dosimetry intercomparison studies reported in literature. The key element of this
methodology is the PC-based computational software LUDEP 2.05, which implements
the new model of the human respiratory tract. Late urinary excretion data of
three male subjects involved in accidental intakes of plutonium aerosols more
than 25 years ago were interpreted in terms of intakes and internal doses with
the aid of the standardized methodology. An important implication of this work is
that late urinary excretion data of the occupational workers of any plutonium
handling facility could be used to show the compliance with the life-time dose
limit.
PMID- 11007466
TI - Self absorption of alpha and beta particles in a fiberglass filter.
AB - Environmental air sampling uses fiberglass filters to collect particulate matter
from the air and then a gas flow detector to measure the alpha and beta activity
on the filter. When counted, the filter is located close to the detector so the
alpha and beta particles emerging from the filter travel toward the detector at
angles ranging from zero to nearly 90 degrees to the normal to the filter
surface. The particles at small angles can readily pass through the filter, but
particles at large angles pass through a significant amount of filter material
and can be totally absorbed. As a result, counting losses can be great. For 4 MeV
alpha particles, the filter used in this experiment absorbs 43% of the alpha
particles; for 7.5 MeV alphas, the absorption is 13%. The measured beta
activities also can have significant counting losses. Beta particles with maximum
energies of 0.2 and 2.0 MeV have absorptions of 44 and 2%, respectively.
PMID- 11007467
TI - Revision of guidelines on limits of exposure to laser radiation of wavelengths
between 400 nm and 1.4 microm. International Commission on Non-Ionizing Radiation
Protection.
PMID- 11007468
TI - Nuclear power plant operating experiences: an international report.
PMID- 11007470
TI - U.K. mobile phone base station study.
PMID- 11007469
TI - NRPB advice on constraints and limits.
PMID- 11007471
TI - A novel cytidine deaminase affects antibody diversity.
PMID- 11007472
TI - BIRinging chromosomes through cell division--and survivin' the experience.
PMID- 11007473
TI - RING finger proteins: mediators of ubiquitin ligase activity.
PMID- 11007474
TI - Class switch recombination and hypermutation require activation-induced cytidine
deaminase (AID), a potential RNA editing enzyme.
AB - Induced overexpression of AID in CH12F3-2 B lymphoma cells augmented class
switching from IgM to IgA without cytokine stimulation. AID deficiency caused a
complete defect in class switching and showed a hyper-IgM phenotype with enlarged
germinal centers containing strongly activated B cells before or after
immunization. AID-/- spleen cells stimulated in vitro with LPS and cytokines
failed to undergo class switch recombination although they expressed germline
transcripts. Immunization of AID-/- chimera with 4-hydroxy-3-nitrophenylacetyl
(NP) chicken gamma-globulin induced neither accumulation of mutations in the NP
specific variable region gene nor class switching. These results suggest that AID
may be involved in regulation or catalysis of the DNA modification step of both
class switching and somatic hypermutation.
PMID- 11007475
TI - Activation-induced cytidine deaminase (AID) deficiency causes the autosomal
recessive form of the Hyper-IgM syndrome (HIGM2).
AB - The activation-induced cytidine deaminase (AID) gene, specifically expressed in
germinal center B cells in mice, is a member of the cytidine deaminase family. We
herein report mutations in the human counterpart of AID in patients with the
autosomal recessive form of hyper-IgM syndrome (HIGM2). Three major abnormalities
characterize AID deficiency: (1) the absence of immunoglobulin class switch
recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3)
lymph node hyperplasia caused by the presence of giant germinal centers. The
phenotype observed in HIGM2 patients (and in AID-/- mice) demonstrates the
absolute requirement for AID in several crucial steps of B cell terminal
differentiation necessary for efficient antibody responses.
PMID- 11007476
TI - Activation of a membrane-bound transcription factor by regulated
ubiquitin/proteasome-dependent processing.
AB - Processing of integral membrane proteins in order to liberate active proteins is
of exquisite cellular importance. Examples are the processing events that govern
sterol regulation, Notch signaling, the unfolded protein response, and APP
fragmentation linked to Alzheimer's disease. In these cases, the proteins are
thought to be processed by regulated intramembrane proteolysis, involving site
specific, membrane-localized proteases. Here we show that two homologous yeast
transcription factors SPT23 and MGA2 are made as dormant ER/nuclear membrane
localized precursors and become activated by a completely different mechanism
that involves ubiquitin/proteasome-dependent processing. SPT23 and MGA2 are
relatives of mammalian NF-kappaB and control unsaturated fatty acid levels.
Intriguingly, proteasome-dependent processing of SPT23 is regulated by fatty acid
pools, suggesting that the precursor itself or interacting partners are sensors
of membrane composition or fluidity.
PMID- 11007478
TI - Molecular structure of human TFIIH.
AB - TFIIH is a multiprotein complex required for both transcription and DNA repair.
Single particles of human TFIIH were revealed by electron microscopy and image
processing at a resolution of 3.8 nm. TFIIH is 16 x 12.5 x 7.5 nm in size and is
organized into a ring-like structure from which a large protein domain protrudes
out. A subcomplex assembled from five recombinant core subunits also forms a
circular architecture that can be superimposed on the ring found in human TFIIH.
Immunolabeling experiments localize several subunits: p44, within the ring
structure, forms the base of the protruding protein density which includes the
cdk7 kinase, cyclin H, and MAT1. Within the ring structure, p44 was flanked on
either side by the XPB and XPD helicases. These observations provide us with a
quartenary organizational model of TFIIH.
PMID- 11007477
TI - Global role for chromatin remodeling enzymes in mitotic gene expression.
AB - Regulation of eukaryotic gene expression requires ATP-dependent chromatin
remodeling enzymes, such as SWI/SNF, and histone acetyltransferases, such as
Gcn5p. Here we show that SWI/SNF remodeling controls recruitment of Gcn5p HAT
activity to many genes in late mitosis and that these chromatin remodeling
enzymes play a role in regulating mitotic exit. In contrast, interphase
expression of GAL1, HIS3, PHO5, and PHO8 is accompanied by SWI/SNF-independent
recruitment of Gcn5p HAT activity. Surprisingly, prearresting cells in late
mitosis imposes a requirement for SWI/SNF in recruiting Gcn5p HAT activity to the
GAL1 promoter, and GAL1 expression also becomes dependent on both chromatin
remodeling enzymes. We propose that SWI/SNF and Gcn5p are globally required for
mitotic gene expression due to the condensed state of mitotic chromatin.
PMID- 11007479
TI - Electron crystal structure of the transcription factor and DNA repair complex,
core TFIIH.
AB - Core TFIIH from yeast, made up of five subunits required both for RNA polymerase
II transcription and nucleotide excision DNA repair, formed 2D crystals on
charged lipid layers. Diffraction from electron micrographs of the crystals in
negative stain extended to about 13 angstrom resolution, and 3D reconstruction
revealed several discrete densities whose volumes corresponded well with those of
individual TFIIH subunits. The structure is based on a ring of three subunits,
Tfb1, Tfb2, and Tfb3, to which are appended several functional moieties: Rad3,
bridged to Tfb1 by SsI1; SsI2, known to interact with Tfb2; and Kin28, known to
interact with Tfb3.
PMID- 11007480
TI - Structure of functionally activated small ribosomal subunit at 3.3 angstroms
resolution.
AB - The small ribosomal subunit performs the decoding of genetic information during
translation. The structure of that from Thermus thermophilus shows that the
decoding center, which positions mRNA and three tRNAs, is constructed entirely of
RNA. The entrance to the mRNA channel will encircle the message when a latch-like
contact closes and contributes to processivity and fidelity. Extended RNA helical
elements that run longitudinally through the body transmit structural changes,
correlating events at the particle's far end with the cycle of mRNA translocation
at the decoding region. 96% of the nucleotides were traced and the main fold of
all proteins was determined. The latter are either peripheral or appear to serve
as linkers. Some may assist the directionality of translocation.
PMID- 11007481
TI - Structural basis for relief of autoinhibition of the Dbl homology domain of proto
oncogene Vav by tyrosine phosphorylation.
AB - Rho-family GTPases transduce signals from receptors leading to changes in cell
shape and motility, mitogenesis, and development. Proteins containing the Dbl
homology (DH) domain are responsible for activating Rho GTPases by catalyzing the
exchange of GDP for GTP. Receptor-initiated stimulation of Dbl protein Vav
exchange activity involves tyrosine phosphorylation. We show through structure
determination that the mVav1 DH domain is autoinhibited by an N-terminal
extension, which lies in the GTPase interaction site. This extension contains the
Tyr174 Src-family kinase recognition site, and phosphorylation or truncation of
this peptide results in stimulation of GEF activity. NMR spectroscopy data show
that the N-terminal peptide is released from the DH domain and becomes
unstructured upon phosphorylation. Thus, tyrosine phosphorylation relieves
autoinhibition by exposing the GTPase interaction surface of the DH domain, which
is obligatory for Vav activation.
PMID- 11007482
TI - Src tyrosine kinase is a novel direct effector of G proteins.
AB - Heterotrimeric G proteins transduce signals from cell surface receptors to
modulate the activity of cellular effectors. Src, the product of the first
characterized proto-oncogene and the first identified protein tyrosine kinase,
plays a critical role in the signal transduction of G protein-coupled receptors.
However, the mechanism of biochemical regulation of Src by G proteins is not
known. Here we demonstrate that Galphas and Galphai, but neither Galphaq,
Galpha12 nor Gbetay, directly stimulate the kinase activity of downregulated c
Src. Galphas and Galphai similarly modulate Hck, another member of Src-family
tyrosine kinases. Galphas and Galphai bind to the catalytic domain and change the
conformation of Src, leading to increased accessibility of the active site to
substrates. These data demonstrate that the Src family tyrosine kinases are
direct effectors of G proteins.
PMID- 11007483
TI - The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase
B/MMP-9 in vivo.
AB - We have identified the key protein substrate of gelatinase B/MMP-9 (GB) that is
cleaved in vivo during dermal-epidermal separation triggered by antibodies to the
hemidesmosomal protein BP180 (collagen XVII, BPAG2). Mice deficient in either GB
or neutrophil elastase (NE) are resistant to blister formation in response to
these antibodies in a mouse model of the autoimmune disease bullous pemphigoid.
Disease develops upon complementation of GB -/- mice with NE -/- neutrophils or
NE -/- mice with GB -/- neutrophils. Only NE degrades BP180 and produces dermal
epidermal separation in vivo and in culture. Instead, GB acts upstream to
regulates NE activity by inactivating alpha1-proteinase inhibitor (alpha1-PI).
Excess NE produces lesions in GB -/- mice without cleaving alpha1-PI. Excess
alpha1-PI phenocopies GB and NE deficiency in wild-type mice.
PMID- 11007484
TI - The polar T1 interface is linked to conformational changes that open the voltage
gated potassium channel.
AB - Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1.
Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel
gating. However, structural alterations of these mutants leave open the question
concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that
gating depends critically on residues at complementary T1 surfaces in an
unusually polar interface. An isosteric mutation in this interface causes
surprisingly little structural alteration while stabilizing the closed channel
and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric
coiled-coil destabilizes the closed channel. Together, these data suggest that
structural changes involving the buried polar T1 surfaces play a key role in the
conformational changes leading to channel opening.
PMID- 11007485
TI - A novel genetic pathway for sudden cardiac death via defects in the transition
between ventricular and conduction system cell lineages.
AB - HF-1 b, an SP1 -related transcription factor, is preferentially expressed in the
cardiac conduction system and ventricular myocytes in the heart. Mice deficient
for HF-1 b survive to term and exhibit normal cardiac structure and function but
display sudden cardiac death and a complete penetrance of conduction system
defects, including spontaneous ventricular tachycardia and a high incidence of AV
block. Continuous electrocardiographic recordings clearly documented cardiac
arrhythmogenesis as the cause of death. Single-cell analysis revealed an anatomic
substrate for arrhythmogenesis, including a decrease and mislocalization of
connexins and a marked increase in action potential heterogeneity. Two
independent markers reveal defects in the formation of ventricular Purkinje
fibers. These studies identify a novel genetic pathway for sudden cardiac death
via defects in the transition between ventricular and conduction system cell
lineages.
PMID- 11007486
TI - A FRET-based sensor reveals large ATP hydrolysis-induced conformational changes
and three distinct states of the molecular motor myosin.
AB - The molecular motor myosin is proposed to bind to actin and swing its light-chain
binding region through a large angle to produce an approximately 10 nm step in
motion coupled to changes in the nucleotide state at the active site. To date,
however, direct dynamic measurements have largely failed to show changes of that
magnitude. Here, we use a cysteine engineering approach to create a high
resolution, FRET-based sensor that reports a large, approximately 70 degree
nucleotide-dependent angle change of the light-chain binding region. The
combination of steady-state and time-resolved fluorescence resonance energy
transfer measurements unexpectedly reveals two distinct prestroke states. The
measurements also show that bound Mg.ADP.Pi, and not bound Mg.ATP, induces the
myosin to adopt the prestroke states.
PMID- 11007488
TI - Why is there late replication?
AB - It has been known for about 40 years that the S phase of the cell cycle is
regulated and that parts of the genome are replicated early, while others are
replicated late. Numerous studies in the past two decades have revealed that
while expressed genes, such as those coding for housekeeping proteins, are
usually replicated early, genes not expressed in a particular cell and
heterochromatic regions of the genome, such as the centromeres or the inactivated
X chromosome of females, are usually replicated late. As details of the
mechanisms leading to the formation of replication complexes were worked out, in
particular for the budding yeast, Saccharomyces cerevisiae, new insights into the
control of the order of replication of genes were obtained that indicate that
this process is highly regulated. It is coordinated with transcription,
epigenetic changes in chromatin structure, regulation of precursor pools and
surveillance mechanisms.
PMID- 11007487
TI - CLIP170-like tip1p spatially organizes microtubular dynamics in fission yeast.
AB - Rod-shaped fission yeast cells grow in a polarized manner, and unlike budding
yeast, the correct positioning of the growth sites at cell ends requires
interphase microtubules. Here we describe a microtubule guidance mechanism that
orients microtubules in the intracellular space along the long axis of the cell,
guiding them to their target region at the cell ends. This mechanism involves
tip1p, a CLIP170-like protein that localizes to distal tips of cytoplasmic
microtubules. In the absence of tip1p, microtubular catastrophe is no longer
restricted to cell ends but occurs when microtubules reach any region of the
cellular cortex. Thus, tip1p enables microtubules to discriminate different
cortical regions and regulates their dynamics accordingly.
PMID- 11007489
TI - The chromosomal distribution of phosphorylated histone H3 differs between plants
and animals at meiosis.
AB - Plant (Secale cereale, Triticum aestivum) and animal (Eyprepocnemis plorans)
meiocytes were analyzed by indirect immunostaining with an antibody recognizing
histone H3 phosphorylated at serine 10, to study the relationship between H3
phosphorylation and chromosome condensation at meiosis. To investigate whether
the dynamics of histone H3 phosphorylation differs between chromosomes with a
different mode of segregation, we included in this study mitotic cells and also
meiotic cells of individuals forming bivalents plus three different types of
univalents (A chromosomes, B chromosomes and X chromosome). During the first
meiotic division, the H3 phosphorylation of the entire chromosomes initiates at
the transition from leptotene to zygotene in rye and wheat, whereas in E. plorans
it does so at diplotene. In all species analyzed H3 phosphorylation terminates
toward interkinesis. The immunosignals at first meiotic division are identical in
bivalents and univalents of A and B chromosomes, irrespective of their equational
or reductional segregation at anaphase I. The grasshopper X chromosome, which
always segregates reductionally, also shows the same pattern. Remarkable
differences were found at second meiotic division between plant and animal
material. In E. plorans H3 phosphorylation occurred all along the chromosomes,
whereas in plants only the pericentromeric regions showed strong immunosignals
from prophase II until telophase II. In addition, no immunolabeling was
detectable on single chromatids resulting from equational segregation of plant A
or B chromosome univalents during the preceding anaphase I. Simultaneous
immunostaining with anti-tubulin and anti-phosphorylated H3 antibodies
demonstrated that the kinetochores of all chromosomes interact with microtubules,
even in the absence of detectable phosphorylated H3 immunosignals. The different
pattern of H3 phosphorylation in plant and animal meiocytes suggests that this
evolutionarily conserved post-translational chromatin modification might be
involved in different roles in both types of organisms. The possibility that in
plants H3 phosphorylation is related to sister chromatid cohesion is discussed.
PMID- 11007490
TI - A neocentromere in the DAZ region of the human Y chromosome.
AB - We describe a novel rearranged human Y chromosome consisting of an inverted
duplication of the long arm heterochromatin and a small amount of euchromatin:
rea(Y)(qter-q11.2::q11.2-qter). The normal centromere has been deleted and a
neocentromere containing CENP-A, -C, -E and Mad2 but not CENP-B has formed close
to the breakpoint. A 2.7 Mb yeast artificial chromosome contig spanning the
breakpoint was constructed and the breakpoint was localised to a region of <120
kb close to the DAZ gene cluster. Combined immunofluorescence and fluorescence in
situ hybridisation showed that the centromeric protein-binding domain of the
neocentromere was located near the breakpoint and within the DAZ cluster.
PMID- 11007491
TI - CENP-G in neocentromeres and inactive centromeres.
AB - CENP-G is a novel constitutive centromere-specific protein localized to the
kinetochore inner plate and subjacent region. It has been identified as
associating specifically with the alpha-1 subfamily of alpha-satellite DNA. In
the present work, the localization of CENP-G was compared with that of other
CENPs by immunofluorescence and fluorescence in situ hybridization. Studies were
carried out on four abnormal human centromeres: two neocentromeres and two
inactive centromeres. CENP-G was detected in one of the two inactive centromeres
but not in the other that shows a partial deletion of the alphoid DNA.
Interestingly, CENP-G is also present in neocentromeres, which lack alphoid DNA
sequences, and in the human Y chromosome, which lacks the alpha-1 type of
satellite DNA. These data provide further evidence that CENP-G may be an
essential factor in centromeric function and that in centromeres lacking the
alpha-1 subfamily of alphoid DNA, other DNA sequences are able to bind CENP-G.
PMID- 11007492
TI - A modifier screen of ectopic Kruppel activity identifies autosomal Drosophila
chromosomal sites and genes required for normal eye development.
AB - Irregular facets (If) is a dominant gain-of-function allele of the Drosophila
segmentation gene Kruppel (Kr) that interferes with eye development. In a search
for genes that interact with Kr activity, we recently performed a systematic
genetic screen to identify dominant enhancers and suppressors of the If eye
phenotype that are located on the third chromosome. Here we describe locations
and candidate genes of the second chromosome that act as dominant modifiers of
ectopic Kr activity during eye development. The collection of more than 40
modifiers of Kr activity located on the second and third chromosomes, from which
a total of 16 genes were identified, includes genes encoding transcription
factors and components of signal transduction pathways that may regulate or be
regulated by Kr activity. We also identified genes coding for more general
cellular factors that could interfere with the intracellular transport or the
half-life of the Kr protein. The data demonstrate that the If mutation provides a
means to screen the Drosophila genome for functional components of developmental
pathways that depend on or can be modified by Kr activity. Owing to the bias of
the screening system applied, these modifier genes will be expressed and are
likely to be required during Drosophila wild-type eye development.
PMID- 11007493
TI - Structural evolution of the germ line-limited chromosomes in Acricotopus.
AB - The elimination of chromatin or whole chromosomes from the future somatic nuclei
during germ line-soma differentiation in early embryogenesis is a genetic
phenomenon found in a wide variety of animal species. Less is known about the
origin, structure, and function of the germ line-limited chromosomes. In the
chironomid Acricotopus lucidus fluorescence in situ hybridization (FISH) with
labeled soma DNA to "Keimbahn" chromosomes (Ks) and soma chromosomes (Ss) of
spermatogonial mitoses revealed that each of the nine different K types possesses
large S-homologous sections, mostly in the distal parts of both chromosome arms.
Painting probes of the three Ss and of each of their chromosome arms were
generated by microdissection of polytene salivary gland chromosomes and
subsequent amplification by the degenerate oligonucleotide-primed polymerase
chain reaction. Multicolor FISH demonstrated that each of the Ks, with the
exception of one K type, was painted by only one of the three S probes.
Furthermore, in seven Ks, one chromosome arm was painted by the long-arm probe
and the other by the short-arm probe of the S concerned. The hybridization
pattern strongly suggests that each of these K types is derived from a specific
S. One function of the S-homologous K sections is thought to be determination of
the regular occurrence of crossover events, with the resulting chiasmata in these
sections ensuring correct segregation of the K homologs during meiosis. Reverse
chromosome painting on polytene S sets with a probe generated from metaphase Ks
corroborates the above results and produces conclusive evidence for the
hypothesis that during evolution the Ks have developed from the Ss by
endopolyploidization and rearrangements followed by the accumulation of germ line
specific repetitive DNA sequences in the centromeric regions.
PMID- 11007494
TI - Invasion of Drosophila virilis by the Penelope transposable element.
AB - The Penelope family of transposable elements (TEs) is broadly distributed in most
species of the virilis species group of Drosophila. This element plays a pivotal
role in hybrid dysgenesis in Drosophila virilis, in which at least four
additional TE families are also activated. Here we present evidence that the
Penelope family of elements has recently invaded D. virilis. This evidence
includes: (1) a patchy geographical distribution, (2) genomic locations mainly
restricted to euchromatic chromosome arms in various geographical strains, and
(3) a high level of nucleotide similarity among members of the family. Two
samples from a Tashkent (Middle Asia) population of D. virilis provide further
support for the invasion hypothesis. The 1968 Tashkent strain is free of Penelope
sequences, but all individuals collected from a 1997 population carry at least
five Penelope copies. Furthermore, a second TE, Ulysses, has amplified and spread
in this population. These results provide evidence for the Penelope invasion of a
D. virilis natural population and the mobilization of unrelated resident
transposons following the invasion.
PMID- 11007495
TI - Genetic induction of chromosomal rearrangements in barley chromosome 7H added to
common wheat.
AB - Chromosome 2C of Aegilops cylindrica induces chromosomal rearrangements in alien
chromosome addition lines, as well as in euploid lines, of common wheat. To
induce chromosomal rearrangements in barley chromosome 7H, reciprocal crosses
were made between a mutation-inducing common wheat line that carries a pair of 7H
chromosomes and one 2C chromosome and a 7H disomic addition line of common wheat.
Many shrivelled seeds were included in the progeny, which was an indication of
the occurrence of chromosome mutations. The chromosomal constitution of the
viable progeny was examined by FISH (fluorescence in situ hybridization) using
the barley subterminal repeat HvT01 as a probe. Structural changes of chromosome
7H were found in about 15% of the progeny of the reciprocal crosses. The aberrant
7H chromosomes were characterized by a combination of N-banding, FISH and genomic
in situ hybridization. Mosaicism for aberrant 7H chromosomes was observed in
seven plants. In total, 89 aberrant 7H chromosomes were identified in 82 plants,
seven of which had double aberrations. More than half of the plants carried a
simple deletion: four short-arm telosomes, one long-arm telosome, and 45 terminal
deletions (23 in the short arm, 21 in the long arm, and one involving both arms).
About 40% of the aberrations represented translocations between 7H and wheat
chromosomes. Twenty of the translocations had wheat centromeres, 12 the 7H
centromere, with translocation points in the 7HS (five) and in the 7HL (seven),
and the remaining four were of Robertsonian type, three involving 7HS and one
with 7HL. In addition, one translocation had a barley segment in an intercalary
position of a wheat chromosome, and two were dicentric. The breakpoints of these
aberrations were distributed along the entire length of chromosome 7H.
PMID- 11007496
TI - Prof. Anthony J. Raimondi.
PMID- 11007497
TI - History of the Korean Neurosurgical Society and future prospects: how should we
educate trainee pediatric neurosurgeons?
PMID- 11007498
TI - Reprint of "Concerning Surgical Intervention for the Intracranial Hemorrhages of
the New-born" by Harvey Cushing, M.D. 1905.
AB - This paper was first presented at a meeting in 1905 and gives an insight into the
problems faced in early neurosurgical operations in newborns and the way they
were approached by an adventurous surgeon.
PMID- 11007499
TI - Sub-galeal coiling of the proximal and distal components of a ventriculo
peritoneal shunt. An unusual complication and proposed mechanism.
AB - We describe the case of a child in whom proximal migration of the peritoneal
catheter and extrusion of the ventricular catheter resulted in the entire
ventriculo-peritoneal shunt along with the shunt chamber (Orbis Sigma II valve)
lying in a sub-galeal pocket in the occipital region in a tightly coiled fashion.
This coiling was very similar in appearance to that of the pre-insertion shunt in
the packaging when it is supplied; hence it is postulated that the migration was
secondary to retained 'memory' of the shunt tubing. This is a rare complication
of ventriculo-peritoneal shunt, which has not been described before.
PMID- 11007500
TI - Basilar artery occlusion in a child: "clot angioplasty" followed by thrombolysis.
AB - Basilar artery occlusions are rare but have a very poor prognosis. Intra-arterial
thrombolysis may produce recanalization and better clinical outcome. A short
delay between the onset of symptoms and thrombolysis is considered essential for
successful recanalization and for the smallest possible risk of haemorrhagic
complications. We present a case of basilar artery occlusion in an 8-year-old
child, which was treated by "clot angioplasty" followed by intra-arterial
thrombolysis. Thirty hours after progressive alteration of consciousness, speech
disturbances and left arm paresis, the child became comatose with decerebrate
rigidity. A CT scan showed parenchymal ischaemic lesions. Angiography (performed
36 h after the onset of symptoms) showed a total occlusion of the basilar artery.
A clot angioplasty was performed by placing a balloon catheter within the
thrombus and inflating it several times in the occluded segment of the basilar
artery. Thrombolysis was then performed through the balloon catheter. The basilar
artery was only partially recanalized at the end of the procedure, but the
perforating arteries of the brain stem had reappeared on angiography. Three
months later the child had completely recovered to a normal clinical status. In
conclusion, the very poor natural prognosis of basilar artery occlusion requires
aggressive management. Recanalization of the basilar artery may be performed even
late after the onset of symptoms. Clot angioplasty allows partial recanalization,
which may increase the efficiency of thrombolysis.
PMID- 11007501
TI - Congenital brain tumor in a neonate conceived by in vitro fertilization.
AB - Congenital brain tumors are very rare; their incidence is estimated at 0.34 per
million live births. We report a case of congenital gliosarcoma in a neonate
conceived by in vitro fertilization (IVF). One other case of brain tumor
(medulloblastoma) is reported in a child born after assisted conception. Whether
these tumors are causally related to the IVF remains obscure.
PMID- 11007502
TI - Craniocerebral injury resulting from transorbital stick penetration in children.
AB - OBJECTS: Two children were admitted to hospital for treatment of craniocerebral
injury with transorbital penetration. METHODS: One child aged 6 years and 6
months had poked a chopstick in his orbit. There was no report of either a
palpebral or an ocular wound. He had subsequently developed a meningeal syndrome
with a cerebral abscess managed by needle aspiration biopsy and intravenous
antibiotics. The other child, aged 4, had fallen onto a metal rod. He presented
with a palpebral wound, motor disorders and coma, all due to a frontal
intracerebral hematoma. There was an improvement in outcome without complications
of an infectious nature or motor sequelae. CONCLUSIONS: Such head injuries are
rare. Clinical, radiological and ophthalmological investigations must be
performed, including computed tomography (CT) scan or cerebral magnetic resonance
imaging (MRI) with antibiotic treatment for suspected microorganisms.
PMID- 11007503
TI - Spinal type IV arteriovenous malformations (perimedullary fistulas) in children.
AB - OBJECTS: Intradural perimedullary spinal arteriovenous fistula (AVF) is a synonym
for type IV spinal arteriovenous malformation (AVM). It is an important clinical
differential diagnosis in all patients with slowly progressive or acute spinal
symptoms. Perimedullary AVFs are rare in the paediatric age group. We report the
treatment regimen and the clinico-radiological findings for these malformations
at our institution. METHODS: Of four paediatric patients, three individuals with
persistent fistulas after endovascular treatment were operated on. The
malformations were obliterated completely in all patients without any morbidity.
In three patients previously documented neurological symptoms resolved during
follow-up. CONCLUSIONS: If slowly progressive or acute radicular or medullary
symptoms arise in children, a spinal arteriovenous malformation should be ruled
out by MRI. A combined endovascular and surgical treatment of paediatric spinal
AVM type IV (perimedullary AVFs) carries a low risk of morbidity and is
reasonably effective.
PMID- 11007504
TI - Aberrant expression of neurotrophic factors in the ventricular progenitor cells
of infant congenitally hydrocephalic rats.
AB - OBJECTS: This study was conducted to investigate the roles of neurotrophic
factors in the development of hydrocephalus in HTX rats. METHODS: Expressions of
brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and fibroblast
growth factor (FGF)-1 were examined immunohistochemically in the cerebral cortex
and ventricular zone of 6-day-old rats with congenital hydrocephalus (HTX rats).
In the ventricular zone of hydrocephalic rats, potent BDNF-like immunoreactivity
(-LI) and weak but significant signals for NT-3- and FGF-1-LIs were observed.
However, no significant signals were detected in non-HTX rats. A small
subpopulation of ventricular cells was positive for microtubule-associated
protein 2 in HTX and non-HTX rats. The positive cells in the HTX rats had
neurites much longer than those in the non-HTX animals, suggesting that some
ventricular cells of the hydrocephalics had ectopically differentiated into
mature neurons. CONCLUSIONS: This abnormal differentiation may have been
responsible for the aberrant expressions of neurotrophic factors. In contrast,
the cerebral neuronal layers did not show such prominent alterations in
neurotrophic factor expression.
PMID- 11007505
TI - Diagnostic steps and staged operative approach in Currarino's triad: a case
report and review of the literature.
AB - The Currarino triad is a combination of a presacral mass, a congenital sacral
bony abnormality and an anorectal malformation. It mostly presents with
constipation. Rectal examination, plain radiographs and magnetic resonance
imaging are the main tools for the diagnosis. If the mass is a meningocele,
colostomy and neurosurgical exploration should precede anoplasty due to the risk
of meningitis. A 14-month-old female patient with anal stenosis, a sacral
scimitar defect and an anterior meningocele is presented in this report.
PMID- 11007506
TI - Nuclear medicine in the next decade. EANM Working Party.
PMID- 11007507
TI - Combination of clinical and V/Q scan assessment for the diagnosis of pulmonary
embolism: a 2-year outcome prospective study.
AB - With the aim of evaluating the efficiency of our diagnostic approach in patients
with suspected acute pulmonary embolism (PE), we prospectively studied 143
patients investigated by means of a ventilation/perfusion (V/Q) lung scan. A pre
test clinical probability of PE (Pclin) was assigned to all patients by the
clinicians and scans were interpreted blinded to clinical assessment. A 2-year
follow-up of our patients was systematically performed and possible in 134 cases.
Distribution of clinical probabilities was high Pclin in 22.5%, intermediate
Pclin in 24% and low Pclin in 53.5%, whereas the distribution of scan categories
was high Pscan in 14%, intermediate Pscan in 18%, low Pscan in 57% and normal
Pscan in 11%. The final prevalence of PE was 24.5%. High Pscan and normal Pscan
were always conclusive (19 and 15 cases respectively). Low Pscan associated with
low Pclin could exclude PE in 43/45 cases (96%). None of the patients in whom the
diagnosis of PE was discarded had a major event related to PE during the 2-year
follow-up. Overall, the combined assessment of clinical and scintigraphic
probabilities allowed confirmation or exclusion of PE in 80% of subjects
(107/134) and proved to be a valuable tool for selecting patients who needed
pulmonary angiography, which was required in 20% of our patients (27/134).
PMID- 11007508
TI - Radioiodine therapy for Plummer's disease based on the thyroid uptake of
technetium-99m pertechnetate.
AB - The aim of this retrospective study was the evaluation of a TcTUs (global
technetium-99m pertechnetate thyroid uptake under suppression)-based approach in
370 patients with thyroid autonomy (Plummer's disease) treated by radioiodine
therapy (RIT) under standardised conditions. The analysis included 370 patients
(309 females, 61 males; mean age 64+/-11.6 years) treated for thyroid autonomy
[unifocal (UFA), 36.8%; multifocal (MFA), 55.7%; disseminated (DISA), 7.6%].
During RIT all patients were under thyroid suppression (TSH< 0.1 microU/ml) and
without thionamide treatment. Of the 370 patients, 73% (n=271) were manifestly
hyperthyroid and 27% (n=99) subclinically hyperthyroid. A dosimetric study
included uptake measurements 24, 48, and 96 h p.i. For dose estimation the
Marinelli algorithm was used. For retrospective definition of the target volume
we used the equation: Autonomous volume = TcTUs x 5. The spectrum of doses given
in our patients ranged from 81 to 1933 Gy. After 18 months of follow-up, RIT was
successful (TSH>0.5 microqU/l and/or TcTUs<1.6%) in 310 patients (84%). Of these
patients, 291 (94%) were euthyroid (with or without L-thyroxine) and 19 (6%)
subclinically hypothyroid (TSH>4 microU/ml). A dose of 350-450 Gy to the
autonomous tissue resulted in a success rate of 97% in the UFA group and 81% in
the MFA/DISA group. Decrease in total thyroid volume and TcTUs did not differ
significantly between successfully treated patients and patients with persistent
autonomy. Multivariate analysis of all 370 patients identified four independent
factors that negatively influenced the therapeutic success: high pretherapeutic
thyroid volume (P=0.0001; odds ratio: 1.017), high pretherapeutic TcTUs values
(P=0.0001; odds ratio: 1.378), multifocal/disseminated autonomy (P=0.0056; odds
ratio: 3.245) and low target dose (P=0.017; odds ratio: 0.997). It is concluded
that the high success rate in the treatment of UFA indicates the concept of TcTUs
based RIT to be valid, but that in the therapy of MFA/DISA the target dose has to
be corrected if the total thyroid volume exceeds a critical threshold.
PMID- 11007509
TI - Changes in myocardial perfusion after catheter-based percutaneous laser
revascularisation.
AB - This study investigated the effect of percutaneous laser revascularisation (PMR)
on regional myocardial blood flow. PMR is a new therapeutic modality for patients
suffering from angina pectoris due to coronary artery disease (CAD) that is not
amenable to revascularisation. Initial clinical studies discovered reduced angina
pectoris and increased exercise capacity after PMR. There are no previous
clinical studies reporting the impact of PMR on perfusion. Thirty-six patients
with end-stage CAD underwent thallium-201 single-photon emission tomography
studies on four different occasions: immediately before PMR and 3, 6 and 12
months following PMR. Each study consisted of pharmacological stress and rest
scintigraphy. Semiquantitative evaluation was performed by use of 14 standardised
wall segments which were classified (a) according to the localisation of the PMR
target region into treated segments, segments adjacent to the treated area and
non-treated segments and (b) according to the pre-therapeutic local perfusion
into four groups: no (0), slight (I), moderate (II) or severe (III) perfusion
deficit. At stress in treated segments of groups II and III local scintigraphic
count densities increased from 60.1% and 34.7% at baseline to 65.3% and 48.3%
after 12 months (P<0.05) while they decreased in segments of group 0 from 94.2%
to 85.7% (P<0.05). In rest studies no changes occurred. Thus, the local rest
stress differences within the target areas become smaller after PMR. In the PMR
target area but not in the nontreated area an improvement in regional myocardial
flow reserve occurs in wall segments with initially severely or moderately
reduced stress perfusion. This effect is consistent with the clinical improvement
after PMR.
PMID- 11007510
TI - 99mTc-MIBI radio-guided minimally invasive parathyroid surgery planned on the
basis of a preoperative combined 99mTc-pertechnetate/99mTc-MIBI and ultrasound
imaging protocol.
AB - The aims of this study were: (a) to define the accuracy of a preoperative
parathyroid imaging protocol based on the combination of technetium-99m
pertechnetate/technetium-99m methoxyisobutylisonitrile (99mTcO4/ 99mTc-MIBI) scan
and neck ultrasound (US) in selecting patients with primary hyperparathyroidism
(pHPT) eligible for a limited neck exploration, and (b) to investigate the
potential role of the intraoperative gamma probe (IGP) in radio-guided minimally
invasive surgery. 99mTcO4/99mTc-MIBI subtraction scan was performed by means of
potassium perchlorate administration with the aim of effecting rapid 99mTcO4 wash
out from the thyroid. Minimally invasive surgery using an IGP was commenced some
minutes following the injection of a low, 70 MBq, 99mTc-MIBI dose. Intraoperative
PTH (i-PTH) was measured. On the basis of preoperative imaging, 21 pHPT
consecutive patients were selected for a limited neck dissection. In 18 of them,
a single parathyroid adenoma was found at surgery and IGP allowed performance of
parathyroidectomy through a small, 2-2.5 cm, skin incision with a relatively
short surgical duration (mean 38 min). i-PTH rapidly normalised in all cases. In
two patients, a parathyroid carcinoma was diagnosed at surgery; consequently, a
wide neck exploration associated with a near-total thyroidectomy was performed.
No loco-regional metastatic lesions were found and i-PTH rapidly normalised after
carcinoma excision. In one patient, i-PTH remained elevated after removal of the
enlarged parathyroid gland which was localised by 99mTcO4/99mTc-MIBI scan and US.
A bilateral exploration was needed to remove a contralateral enlarged parathyroid
gland. Combined, 99mTcO4/99mTc-MIBI scan and US imaging correctly localised a
single parathyroid gland in 20/21 patients (95.2%); thus, this protocol appears
to be accurate enough for the preoperative selection of pHPT patients eligible
for limited neck surgery. Moreover, in these selected patients the IGP seems to
be helpful in performing radio-guided minimally invasive surgery.
PMID- 11007511
TI - FDG-PET for detection of osseous metastases from malignant primary bone tumours:
comparison with bone scintigraphy.
AB - The purpose of this study was to compare positron emission tomography using
fluorine-18 fluorodeoxyglucose (FDG-PET) and technetium-99m methylene
diphosphonate (MDP) bone scintigraphy in the detection of osseous metastases from
malignant primary osseous tumours. In 70 patients with histologically proven
malignant primary bone tumours (32 osteosarcomas, 38 Ewing's sarcomas), 118 FDG
PET examinations were evaluated. FDG-PET scans were analysed with regard to
osseous metastases in comparison with bone scintigraphy. The reference methods
for both imaging modalities were histopathological analysis, morphological
imaging [additional conventional radiography, computed tomography (CT) or
magnetic resonance imaging (MRI)] and/or clinical follow-up over 6-64 months
(median 20 months). In 21 examinations (18%) reference methods revealed 54
osseous metastases (49 from Ewing's sarcomas, five from osteosarcomas). FDG-PET
had a sensitivity of 0.90, a specificity of 0.96 and an accuracy of 0.95 on an
examination-based analysis. Comparable values for bone scintigraphy were 0.71,
0.92 and 0.88. On a lesion-based analysis the sensitivity of FDG-PET and bone
scintigraphy was 0.80 and 0.72, respectively. Analysing only Ewing's sarcoma
patients, the sensitivity, specificity and accuracy of FDG-PET and bone scan were
1.00, 0.96 and 0.97 and 0.68, 0.87 and 0.82, respectively (examination-based
analysis). None of the five osseous metastases from osteosarcoma were detected by
FDG-PET, but all of them were true-positive using bone scintigraphy. In
conclusion, the sensitivity, specificity and accuracy of FDG-PET in the detection
of osseous metastases from Ewing's sarcomas are superior to those of bone
scintigraphy. However, in the detection of osseous metastases from osteosarcoma,
FDG-PET seems to be less sensitive than bone scintigraphy.
PMID- 11007512
TI - Cholecystokinin receptor imaging using an octapeptide DTPA-CCK analogue in
patients with medullary thyroid carcinoma.
AB - Cholecystokinin (CCK)-B receptors have been demonstrated on a high percentage of
medullary thyroid carcinomas (MTC) in vitro. After encouraging results both in
vitro and in animal studies, we studied the efficacy of an octapeptide [111In
DTPA]-CCK analogue in seven patients with MTC. In four of five patients in whom
serum calcitonin levels were monitored, a significant rise was found following
the injection, indicating retained biological activity of the radiopeptide. In
all patients there was visualization of the CCK-B receptor-positive stomach. In
one of two patients with known MTC lesions, some of the lesions were visualized;
in addition some lesions were visualized in one of the five other patients who
had elevated serum tumour markers but negative localizing studies. Radioactivity
in the presumed tumour sites was still present at 48 h p.i. The uptake in the
presumed tumour sites and stomach was low. Background radioactivity dropped
rapidly owing to urinary excretion. After 1 h, breakdown products of the labelled
analogue predominated both in urine and in serum, and virtually no intact peptide
was present. IN CONCLUSION: (1) the CCK-B receptor-positive gastric mucosa and
presumed MTC lesions could be visualized in patients using an octapeptide [111In
DTPA]-CCK analogue that is probably internalized, proving the feasibility of CCK
B receptor imaging in vivo; (2) there was a relatively low uptake of the CCK
analogue in the strongly CCK receptor positive stomach, and rapid degradation of
the peptide in serum.
PMID- 11007513
TI - 99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging
somatostatin receptor-positive tumours; first clinical results and intra-patient
comparison with 111In-labelled octreotide derivatives.
AB - [111In-diethylene triamine penta-acetic acid-D-Phe1]-octreotide (DTPA-octreotide)
scintigraphy has gained widespread acceptance as a diagnostic clinical procedure
in oncology for imaging somatostatin receptor-positive tumours. However, indium
111 as a radiolabel has several drawbacks, including limited availability,
suboptimal gamma energy and high radiation burden to the patient. We have
recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new
octreotide derivative which showed promising results both in vitro and in vivo.
We now report our initial clinical experiences with this new radiopharmaceutical
in ten oncological patients. The clinical diagnoses were: carcinoid syndrome
(n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1).
The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those
of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five
cases. With the new tracer tumours were imaged within 15 min after injection and
showed the highest target/non-target ratios 4 h after injection. Tumour uptake
persisted up to 20 h p.i. The rate of blood clearance was similar to that of
111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary
excretion was lower compared with the 111In derivatives. Semi-quantitative region
of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher
tumour/organ (target/non-target) ratios than the 111In derivatives, especially in
relation to heart and muscle. Significantly more lesions could be detected in
99mTc images. We conclude that 99mTcEDDA/HYNIC-TOC shows better imaging
properties for the identification of somatostatin receptor-positive tumour sites
than currently available 111In-labelled octreotide derivatives.
PMID- 11007514
TI - Biodistribution and dosimetry of [123I]iodo-PK 11195: a potential agent for SPET
imaging of the peripheral benzodiazepine receptor.
AB - The highest concentrations of the peripheral benzodiazepine receptor (PBR) are
found in the kidneys and heart. In addition, the PBR has been reported to reflect
neuro-inflammatory damage by co-localisation with activated microglia. PK 11195
is a high-affinity ligand for the PBR. The aim of this study was to investigate
in humans the biodistribution and dosimetry of [123I]iodoPK 11195, a potential
single-photon emission tomography tracer for the PBR. Five healthy volunteers
were injected with 112 MBq of [123I]iodo-PK 11195. Sequential whole-body scans
were performed up to 72 h post injection. Multiple blood samples were taken, and
urine was collected to measure the fraction voided by the renal system. Decay
corrected regions of interest of the whole-body images were analysed, and
geometric mean count rates were used to determine organ activity. Organ absorbed
doses and effective dose were calculated using the MIRD method. [123I]iodo-PK
11195 was rapidly cleared from the blood, mainly by the hepatobiliary system.
Approximately 22% was voided in urine after 48 h. Average organ residence times
were 0.74, 0.44 and 0.29 h for the liver, upper large intestine and lower large
intestine, respectively. The testes received the highest dose, 109.4 microGy/MBq.
All other organs investigated received doses of less than 50 microGy/MBq. The
effective dose was 40.3 microSv/MBq. In conclusion, [123I]iodo-PK 11195 is a
suitable agent for the visualisation of the PBR and indirectly for the imaging of
neuro-inflammatory lesions. Taking into account the radiation burden of 7.46 mSv
following an administration of 185 MBq, a [123I]iodo-PK 11195 investigation has
to be considered an ICRP risk category IIb investigation.
PMID- 11007515
TI - Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with
markedly high specific activity with minimal loss of immunoreactivity.
AB - For the purpose of radioimmunotherapy, labelling of monoclonal antibody with high
specific activity is often necessary, especially when using a radionuclide with a
shorter half-life. Polyamine dendrimers (PAMAM) are novel synthetic polymeric
molecules with large numbers of amine residues on their spherical surface. In
order to bind large numbers of radiometals to single antibody molecules, the
generation-4 PAMAM (G4), which has 64 amines, was conjugated with 43 molecules of
2-(p-isothiocyanatobenzyl)-6-methyl-diethylene triamine penta-acetic acid (1B4M),
a derivative of DTPA. This product [G4-(1B4M)43] was then conjugated with OST7, a
murine monoclonal IgG1. We evaluated the achievable specific activity for 111In
labeling, immunoreactivity, biodistribution, and tumor targeting in mice of the
111In- or 153Gd-OST7-G4-(1B4M)43 as compared with radiolabeled OST7-1B4M or 56C
1B4M. The maximum specific activity of 111In-OST7-G4-(1B4M)43 and 111In-OST7-1B4M
was 470 and 8.7 GBq/mg (12,700 and 263 mCi/mg), respectively. Immunoreactivity of
radiolabeled OST7-G4-(1B4M)43 and OST7-1B4M, as determined by the binding to
KT005 cells expressing the antigen, was respectively 91% and 84% of that of 125I
labelled OST7. Biodistribution studies for preparations with maximum specific
activity in normal mice 3 h after injection showed that 111In- or 153Gd-OST7-G4
(1B4M)43 cleared faster from the blood and accumulated more in the liver than did
111In- or 153Gd-OST7-1B4M. The dendrimer 1B4M [G4-(1B4M)64] itself showed similar
saturation effects with metals. The radioactivity in all the other organs
reflected the rapid clearance of radioactivity from the blood. 153Gd-OST7-G4
(1B4M)43 showed specific accumulation in the KT005 tumor. In conclusion, we could
successfully bind 49 times as many metal atoms to an antibody molecule as is
possible with conventional metal labeling for indium and gadolinium, and did so
with minimal loss of immunoreactivity. When we achieved radiolabeling with
maximum specific activity, Gd conjugate showed better biodistribution than In
conjugate.
PMID- 11007517
TI - Influence of arm positioning on tomographic thallium-201 myocardial perfusion
imaging and the effect of attenuation correction.
AB - Lateral attenuation in single-photon emission tomography (SPET) myocardial
perfusion imaging (MPI) has been attributed to the left arm if it is held by the
patient's side during data acquisition. As a result MPI data are conventionally
acquired with the arms held above the head. The aims of this study were to
determine the effect of imaging arms down on reconstructed tomographic images
depicting regional myocardial thallium-201 distribution and to assess whether
attenuation-corrected (AC) myocardial perfusion images acquired arms down could
replace uncorrected (NC) images acquired arms up for routine clinical service.
Twenty-eight patients referred for routine MPI underwent sequential 180 degrees
emission/transmission imaging for attenuation correction using an L-shaped dual
headed gamma camera (GE Optima) fitted with two gadolinium-153 scanning line
sources. Delay data were acquired twice: once supine with the arms up and then
supine with the arms down. Detector radius of rotation (ROR) for arms up and arms
down studies was recorded. For each data set, count density was measured in 17
segments of a polar plot and segmental uptake expressed relative to study
maximum. Oblique images were assessed qualitatively by two observers blinded to
study type for tracer distribution and overall quality. Transmission maps were
assessed for truncation. Mean detector ROR was 190 mm for arms-up studies and 232
mm for arms-down studies (P<0.05). Population mean segmental relative uptake
values for NC arms-up studies were higher than for NC arms-down studies, with the
greatest difference seen anterolaterally. Nevertheless, the majority (24/28) of
oblique NC arms-up and NC arms-down images appeared similar and only four (14%)
NC arms-down studies showed additional areas of reduced count density (one
anterior and three lateral). Corresponding AC arms-down studies showed that count
density within the anterior defect improved to normal but the lateral reductions
persisted, and in two of these three studies the arms-down transmission map was
distorted. Population mean segmental relative uptake values for NC arms-down
studies were lower than for AC arms-down studies apart from three anterolateral
segments where NC arms-down values were higher. Of 28 AC arms-down studies, 11
(39%) were of reduced quality compared with NC arms-up studies because of poorer
spatial resolution and because AC enhances liver activity compared with NC. It is
concluded that arm positioning influences reconstructed tomographic images
depicting regional 201T1 distribution, particularly anterolaterally. There is
lateral undercorrection in approximately 10% of AC arms-down studies, possibly
because of attenuation map truncation. Image quality is reduced in about one
third of AC armsdown studies compared with NC arms-up studies. These data suggest
that this attenuation correction method is not sufficiently robust to allow
routine acquisition of MPI data with the arms down.
PMID- 11007516
TI - Significant regional heterogeneity of coronary flow reserve in paediatric
hypertrophic cardiomyopathy.
AB - Previous studies have indicated that cardiac events in young patients with
hypertrophic cardiomyopathy (HCM) are related to ischaemia rather than to
arrhythmia. We measured coronary flow reserve in paediatric HCM and compared the
values with those in adult HCM. We studied 12 patients with HCM including six
paediatric (<20 years old; mean 13 years) and six adult patients (>20 years old:
mean 62 years), and six healthy young adults (mean 29 years) as controls. Every
patient underwent magnetic resonance imaging (MRI) for anatomical assessment.
Myocardial blood flow at rest and after dipyridamole infusion was measured with
dynamic nitrogen-13 ammonia positron emission tomography (PET). Partial volume
effect was corrected for using the anatomical data obtained with MRI. In adult
patients with HCM, coronary flow reserve in the hypertrophied septal region was
not significantly different from that in the non-hypertrophied lateral wall
(1.38+/-0.29 vs 1.77+/-0.39, respectively). In the paediatric patients, coronary
flow reserve in the hypertrophied septal region was significantly lower than in
the non-hypertrophied lateral wall (0.84+/-0.33 vs 2.74+/-0.90, respectively,
P<0.01). In addition, coronary flow reserve in adult patients was lower than in
control subjects both in the septal wall (1.38+/-0.29 vs 2.94+/-0.35,
respectively, P<0.0001) and in the lateral wall (1.77+/-0.39 vs 2.85+/-0.69,
respectively, P<0.05). In contrast, coronary flow reserve in paediatric patients
was not significantly different from that in control subjects in the lateral wall
(2.74+/-0.90 vs 2.85+/-0.69, respectively), while absolute reduction of
myocardial blood flow was noted after pharmacological vasodilatation in the
hypertrophied septal region. In conclusion, significant regional differences of
coronary flow reserve were present in the paediatric patients with HCM. These
results suggest that paediatric patients with HCM intrinsically have the
potential to experience significant regional ischaemia even in the absence of
coronary stenosis.
PMID- 11007518
TI - Should scatter be corrected in both transmission and emission data for accurate
quantitation in cardiac SPET?
AB - Ideally, reliable quantitation in single-photon emission tomography (SPET)
requires both emission and transmission data to be scatter free. Although scatter
in emission data has been extensively studied, it is not well known how scatter
in transmission data affects relative and absolute quantitation in reconstructed
images. We studied SPET quantitative accuracy for different amounts of scatter in
emission and transmission data using a Utah phantom and a cardiac Data Spectrum
phantom including different attenuating media. Acquisitions over 180 degrees were
considered and three projection sets were derived: 20% images and Jaszczak and
triple-energy-window scatter-corrected projections. Transmission data were
acquired using gadolinium-153 line sources in a 90-110 keV window using a narrow
or wide scanning window. The transmission scans were performed either
simultaneously with the emission acquisition or 24 h later. Transmission maps
were reconstructed using filtered backprojection and mu values were linearly
scaled from 100 to 140 keV. Attenuation-corrected images were reconstructed using
a conjugate gradient minimal residual algorithm. The mu value underestimation
varied between 4% with a narrow transmission window in soft tissue and 22% with a
wide window in a material simulating bone. Scatter in the emission and
transmission data had little effect on the uniformity of activity distribution in
the left ventricle wall and in a uniformly hot compartment of the Utah phantom.
Correcting the transmission data for scatter had no impact on contrast between a
hot and a cold region or on signal-to-noise ratio (SNR) in regions with uniform
activity distribution, while correcting the emission data for scatter improved
contrast and reduced SNR. For absolute quantitation, the most accurate results
(bias <4% in both phantoms) were obtained when reducing scatter in both emission
and transmission data. In conclusion, trying to obtain the same amount of scatter
in emission and transmission data, in addition to being impractical because of
the difficulty in knowing the precise scatter components, did not yield such
accurate absolute activity quantitation as when emission and transmission scatter
were reduced.
PMID- 11007519
TI - Impact of attenuation correction on the accuracy of FDG-PET in patients with
abdominal tumors: a free-response ROC analysis.
AB - The aim of this study was to evaluate image quality and lesion detectability with
and without attenuation correction in patients with abdominal tumors, using a
free-response receiver operating characteristic (FROC) methodology. Thirty-four
patients with various abdominal tumors were evaluated (11 men, 23 women, median
age 48 years). Whole-body emission scans were performed 68 min (35-102 min) after
intravenous injection of 4.3 MBq/kg fluorine-18 fluorodeoxyglucose (FDG). Images
were reconstructed using the OS-EM algorithm and corrected for attenuation either
using postinjection singles transmission (n=27) or by calculation and body
outline (n=7). Total scan duration did not exceed 70 min. Studies were read
independently by four observers unaware of any clinical data. The uncorrected
(UC) images were systematically read before the attenuation-corrected (AC)
images. All studies were given an image quality score ranging from 1 (unreadable)
to 5 (excellent). Each focus of increased activity was then localized and given a
probability of malignancy using a five-point scale. The average image quality
score was similar for both UC and AC images. At the time of the positron emission
tomography (PET) scans, 127 lesions (63 liver metastases, 9 retroperitoneal
lesions, 50 peritoneal or bowel lesions, and 5 pancreatic carcinomas) were
revealed by pathological or correlative studies. The areas under the FROC curves
were consistently greater for AC images (range 0.8663-0.8867) than for UC images
(range 0.7774 -0.8613). Overall, the difference between the AC images and the UC
images was significant (P=0.019). In particular, correction for attenuation
increased the sensitivity regardless of the location of the lesions. In
conclusion, correction for attenuation significantly improves the diagnostic
accuracy of FDG-PET for abdominal staging of neoplasms, without impairing the
image quality.
PMID- 11007520
TI - Gated SPET quantification of small hearts: mathematical simulation and clinical
application.
AB - Quantification of gated single-photon emission tomography (SPET) in small hearts
has been considered to be inaccurate. To evaluate the validity of gated SPET in a
small chamber volume, mathematical simulation and clinical application to
paediatric patients were performed. Myocardium with various chamber sizes from 14
ml to 326 ml was generated assuming an arbitrary resolution (6.9-15.7 mm in full
width at half-maximum), noise and zooming factors. The cut-off frequency of the
Butterworth filter for preprocessing was varied from 0.16 to 0.63 cycles/cm. The
chamber volume was calculated by quantitative gated SPET software (QGS). The
patients, aged 2 months to 19 years (n=27), were studied by gated technetium-99m
methoxyisobutylisonitrile or tetrofosmin SPET. Image magnification as large as
possible was performed during data acquisition to include the whole chest using
1.25-2.0 zooming. Based on the simulation study, an underestimation of the
chamber volume occurred below a volume of 100 ml. The degree of underestimation
for a 37-ml volume was 49% without zooming, but it improved to 3% with 2x
zooming. Filters with a higher cut-off frequency, better system resolution and
hardware zooming during acquisition improved quantitative accuracy in small
hearts. For the subjects under 7 years old (n=7), quantification of volume and
ejection fraction (EF) was possible in 72% of the patients. In those over 7 years
old, gated SPET quantification was feasible in all cases. The correlation between
gated SPET end-diastolic volume (SPET EDV) and both echocardiographic end
diastolic dimension (EDD) and echocardiographic EDV was good (r=0.84 between SPET
EDV and echo EDD, r=0.85 between SPET EDV and echo EDV, P<0.0001 for both). The
correlation between gated SPET EF and both echocardiographic fractional
shortening (FS) and echocardiographic EF was fair (r=0.69 between SPET EF and
echo FS, r=0.72 between SPET EF and echo EF, P<0.0001 for both). In conclusion,
quantification of gated SPET of small hearts can be improved by means of a SPET
filter with a high cut-off frequency, high system resolution and appropriate
zooming. Gated SPET should be attempted not only in patients with small hearts
but also in paediatric patients.
PMID- 11007521
TI - Improvement of brain perfusion SPET using iterative reconstruction with scatter
and non-uniform attenuation correction.
AB - Filtered back-projection (FBP) is generally used as the reconstruction method for
single-photon emission tomography although it produces noisy images with apparent
streak artefacts. It is possible to improve the image quality by using an
algorithm with iterative correction steps. The iterative reconstruction technique
also has an additional benefit in that computation of attenuation correction can
be included in the process. A commonly used iterative method, maximum-likelihood
expectation maximisation (ML-EM), can be accelerated using ordered subsets (OS
EM). We have applied to the OS-EM algorithm a Bayesian one-step late correction
method utilising median root prior (MRP). Methodological comparison was performed
by means of measurements obtained with a brain perfusion phantom and using
patient data. The aim of this work was to quantitate the accuracy of iterative
reconstruction with scatter and non-uniform attenuation corrections and post
filtering in SPET brain perfusion imaging. SPET imaging was performed using a
triple-head gamma camera with fan-beam collimators. Transmission and emission
scans were acquired simultaneously. The brain phantom used was a high-resolution
three-dimensional anthropomorphic JB003 phantom. Patient studies were performed
in ten chronic pain syndrome patients. The images were reconstructed using
conventional FBP and iterative OS-EM and MRP techniques including scatter and
nonuniform attenuation corrections. Iterative reconstructions were individually
post-filtered. The quantitative results obtained with the brain perfusion phantom
were compared with the known actual contrast ratios. The calculated difference
from the true values was largest with the FBP method; iteratively reconstructed
images proved closer to the reality. Similar findings were obtained in the
patient studies. The plain OS-EM method improved the contrast whereas in the case
of the MRP technique the improvement in contrast was not so evident with post
filtering.
PMID- 11007522
TI - Comparison of internal radiation doses estimated by MIRD and voxel techniques for
a "family" of phantoms.
AB - The aim of this study was to use a new system of realistic voxel phantoms, based
on computed tomography scanning of humans, to assess its ability to specify the
internal dosimetry of selected human examples in comparison with the well
established MIRD system of mathematical anthropomorphic phantoms. Differences in
specific absorbed fractions between the two systems were inferred by using organ
dose estimates as the end point for comparison. A "family" of voxel phantoms,
comprising an 8-week-old baby, a 7-year-old child and a 38-year-old adult, was
used and a close match to these was made by interpolating between organ doses
estimated for pairs of the series of six MIRD phantoms. Using both systems, doses
were calculated for up to 22 organs for four radiopharmaceuticals with widely
differing biodistribution and emission characteristics (technetium-99m
pertechnetate, administered without thyroid blocking; iodine-123 iodide; indium
111 antimyosin; oxygen-15 water). Organ dose estimates under the MIRD system were
derived using the software MIRDOSE 3, which incorporates specific absorbed
fraction (SAF) values for the MIRD phantom series. The voxel system uses software
based on the same dose calculation formula in conjunction with SAF values
determined by Monte Carlo analysis at the GSF of the three voxel phantoms.
Effective doses were also compared. Substantial differences in organ weights were
observed between the two systems, 18% differing by more than a factor of 2. Out
of a total of 238 organ dose comparisons, 5% differed by more than a factor of 2
between the systems; these included some doses to walls of the GI tract, a
significant result in relation to their high tissue weighting factors. Some of
the largest differences in dose were associated with organs of lower significance
in terms of radiosensitivity (e.g. thymus). In this small series, voxel organ
doses tended to exceed MIRD values, on average, and a 10% difference was
significant when all 238 organ doses were considered as a single group. In 12
comparisons of effective dose, the mean voxel to MIRD ratio was 1.07 (range 0.72
1.32). It was shown for the majority of cases that, whereas some large
differences in SAF values exist, differences in source organ and effective dose
values between the MIRD and voxel methods were largely accounted for by the
respective organ mass differences. The reasons for various organ dose differences
with the selected radiopharmaceuticals are discussed. Taking biological variation
into account, there is reasonable agreement between the two methods but some
significant differences exist that warrant further investigation. More extensive
comparisons involving a wide variety of voxel phantoms are required to establish
whether realistic voxel phantoms should eventually replace the MIRD system.
PMID- 11007523
TI - Detecting the sentinel lymph node in patients with differentiated thyroid
carcinoma.
AB - The aim of this study was to evaluate sentinel lymph node mapping in patients
with differentiated thyroid carcinoma. Nine patients with suspected thyroid
carcinoma who were scheduled to undergo thyroidectomy underwent scintigraphic
localization of sentinel lymph nodes (SLNs). On the day of surgery we injected 37
MBq technetium-99m nanocolloid intratumourally. Dynamic data up to 10 min
followed by planar anterior and lateral oblique images up to 1 h after tracer
administration were recorded. At surgery the primary tumour was excised first,
then the SLNs were removed using a gamma probe. Four patients had papillary
carcinoma, two follicular carcinoma, one an oncocytic tumour and two benign
tumours. An SLN was identified in all four patients with papillary carcinoma. In
the two patients with follicular carcinoma, SLN detection failed. Five patients
had one radioactive node, one had three and one had four. In one patient, no SLN
was visible with scintigraphic imaging but at surgery three SLNs could be clearly
identified using the gamma probe after removal of the primary tumour. There were
no false-negative findings. This initial study indicates that in patients with
papillary thyroid carcinoma detection of the SLN is possible, whereas the
technique failed in two patients with follicular carcinoma. A study on a larger
patient sample is now warranted.
PMID- 11007524
TI - Technetium-99m DTPA inhalation scintigraphy in patients treated with fluoxetine
and maprotiline: preliminary results.
AB - Drug-metabolising enzymatic activities have been detected in tracheobronchiolar,
bronchiolar and alveolar regions in the lungs. Induction of phospholipidosis by
amine drugs such as clorphentermine has also been shown. This study aimed to
investigate the effect of fluoxetine and maprotiline, which contain amine groups
in their structure, on pulmonary epithelial membrane permeability. Twenty-seven
patients (mean age 36+/-12 years) with various psychiatric problems, of whom 17
were treated with fluoxetine and 10 with maprotiline, were included in this
study. Technetium-99m diethylene triamine penta-acetic acid (DTPA) aerosol
inhalation scintigraphy was performed before and after 4-6 weeks of therapy.
Following the inhalation of 1480 MBq 99mTc-DTPA for 3 min, lung images in a 64x64
matrix were obtained every minute for 30 min. Regions of interest were drawn
around the periphery of the lungs and on the major airways. Clearance half-times
(T 1/2) were calculated by placing a mono-exponential fit on the curves.
Penetration index (PI) was calculated on the first-minute image. There was no
difference between the clearance rates of 99mTc-DTPA before and after therapy for
either the fluoxetine or the maprotiline group. After therapy, a significant
decrease in PI was found in patients treated with fluoxetine (PI values before
and after therapy: 0.53+/-0.03 and 0.49+/-0.05 respectively, P< or =0.05). This
finding might have been due to the induction of increased synaptic serotonin (5
HT) by fluoxetine, which acts by inhibiting the re-uptake of 5-HT on presynaptic
membranes. Bronchoconstriction of small and medium airways may be caused by
direct and indirect effects of 5-HT on smooth muscle contraction.
PMID- 11007525
TI - 99mTc(V)DMSA quantitatively predicts 188Re(V)DMSA distribution in patients with
prostate cancer metastatic to bone.
AB - Rhenium-188 dimercaptosuccinic acid complex [188Re(V)DMSA], a potential
therapeutic analogue of the tumour imaging agent 99mTc(V)DMSA, is selectively
taken up in bone metastases in patients with prostate cancer. It would be helpful
in planning palliative radionuclide therapy if 99mTc(V)DMSA could be used to
predict tumour and kidney retention of 188Re(V)DMSA. The aim of this study was to
determine the correlation between tumour-to-normal tissue ratios and kidney-to
soft tissue ratios of 99mTc(V)DMSA and 188Re(V)DMSA. This would determine whether
a scan with 99mTc(V) DMSA could be used to identify patients for whom
188Re(V)DMSA treatment would be contra-indicated, and enable prediction of
relative kidney and tumour radiation absorbed dose in 188Re(V)DMSA treatment. Ten
patients with prostate carcinoma were recruited following observation of
disseminated bone metastases on a recent 99mTc-hydroxydiphosphonate bone scan.
Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and
injection of 600 MBq 99mTc(V)DMSA, and a week later, at similar times after
hydration and injection of 370 MBq 188Re(V)DMSA. A triple-energy window (TEW)
scatter correction was applied to the 188Re scans. Counts per pixel were
determined in regions of interest drawn over metastatic sites, kidneys and normal
soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor
of approximately 0.8 after the TEW was applied) on 188Re scans than on 99mTc
scans, but the two were highly linearly correlated both in all individual
patients and in tumours pooled from all patients together both at 4 h and at 24
h. Kidney-to-soft tissue ratios were similarly correlated and were lower for
188Re than for 99mTc by a similar factor. Both tumour- and kidney-to-soft tissue
ratios increased between 4 and 24 h but the latter increased more. In conclusion,
only minor differences were seen between 99mTc and 188Re scans, and kidney-to
background ratios on 188Re scans were not higher than on 99mTc scans. These
differences are insufficient to infer that they are due to a real difference in
biodistribution, and they may be due only to different physical imaging
characteristics. Thus 99mTc(V)DMSA scans are predictive of 188Re(V)DMSA
biodistribution and could be used to estimate tumour and renal dosimetry and
assess suitability of patients for 188Re(V)DMSA treatment.
PMID- 11007526
TI - Impaired dopaminergic neurotransmission in patients with traumatic brain injury:
a SPECT study using 123I-beta-CIT and 123I-IBZM.
AB - Structural imaging suggests that traumatic brain injury (TBI) may be associated
with disruption of neuronal networks, including the nigrostriatal dopaminergic
pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic
neurotransmission have not been demonstrated in TBI using functional imaging. We
therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta
carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide
(IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score
(+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average
141 days (SD +/-92) after TBI. The SPET images were compared with structural
images using cranial computerised tomography (CCT) and magnetic resonance imaging
(MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity
ratios of striatal to cerebellar uptake were used as a semiquantitative parameter
of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared
with age-matched controls, patients with TBI had significantly lower
striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the
DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed
varying cortical and subcortical lesions, with the frontal lobe being most
frequently affected whereas the striatum appeared structurally normal in all but
one patient. Our findings suggest that nigrostriatal dysfunction may be detected
using SPET following TBI despite relative structural preservation of the
striatum. Further investigations of possible clinical correlates and efficacy of
dopaminergic therapy in patients with TBI seem justified.
PMID- 11007527
TI - Experience with carbon-11 choline positron emission tomography in prostate
carcinoma.
AB - We investigated the potential of carbon-11 choline positron emission tomography
(PET) for the detection of lymph node and bone metastases in prostate cancer. A
total of 23 patients were studied (known metastases: 8; suspicion of metastases:
3; primary staging: 12). Whole-body PET imaging was performed 5 min after
injection of the tracer and completed within 1 h. Focally increased tracer uptake
in bone or abdominal lymph node regions was interpreted as representing tumour
involvement. All known bone and lymph node metastases could be recognized by
[11C]choline PET. One out of ten negative scans for primary staging was false
negative (lymph node <1 cm) and one out of two positive scans was false-positive
with regard to lymph node involvement (focal bowel activity). It is concluded
that [11C]choline PET is a promising new tool for the primary staging of prostate
cancer, with lymph node and bone metastases demonstrating high tracer uptake.
Therapeutic management could be influenced by these results in that the technique
may permit avoidance of surgical lymph node exploration.
PMID- 11007528
TI - The importance of the control group in functional brain imaging.
PMID- 11007529
TI - Radiolabeled estradiol derivatives to predict response to hormonal treatment in
breast cancer: a review.
AB - Several radiolabeled steroidal and nonsteroidal estradiol derivatives of which
the tumoral uptake is believed to relate quantitatively to the content and
binding characteristics of the alpha-estrogen receptor (alphaER) receptor in the
target tissue have been synthesized and their imaging potential and clinical
usefulness evaluated in vivo in humans. Due to the use of different methodologies
and cut-off values for the measurement of alphaER positivity, the use of both
quantitative positron emission tomography and semiquantitative single-photon
emission tomography, and the difference in patient populations studied, direct
comparison of these data is not possible. Individual data, however, fail to
substantiate a direct relationship between these radiolabeled estradiol
derivatives and alphaER status, in keeping with recent pathophysiological
findings demonstrating (1) estradiol sequestration and retention through other
than alphaER-mediated, either membrane- or non-membrane-related, mechanisms and
(2) an inverse relationship between estradiol uptake and local biosynthesis
through aromatization and interconversion in alphaER-positive tumors.
Additionally, given the discovery of very high affinity alphaER-like binding
sites (Kd, dissociation constant, <0.1 nM), and the potential for underestimation
of aER Kd when using ligand binding assays, at least part of the radiolabeled
estradiol derivative uptake reflects tumoral perfusion rather than the ligand
receptor binding process. However, the reduction in cellular uptake, membrane
sequestration and local biosynthesis of estradiol following tamoxifen treatment
in alphaER-responsive tumors should allow early prediction of response to therapy
through rapid sequential radiolabeled estradiol scintigraphy with higher accuracy
than conventional alphaER estimations, as supported by recent data.
PMID- 11007531
TI - Effects of soybean lipoxygenase on Na+/K+-ATPase activity in vitro.
AB - Oxidized metabolites of polyunsaturated fatty acids produced by lipoxygenase are
among the endogenous regulators of Na+/K+-ATPase. The direct effect of
lipoxygenase on Na+/K+-ATPase activity was assessed in vitro using soybean
lipoxygenase. Treatment of 4.2 microg/mL Na+/K+-ATPase (from dog kidneys) with
4.2 microg/mL of soybean lipoxygenase caused 20+/-2% inhibition of ATPase
activity. A 10-fold increase in lipoxygenase concentration (41.6 microg/mL) led
to 30+/-0.3% inhibition. In the presence of 12 microg/mL phenidone (a
lipoxygenase inhibitor) and 15.4 microg/mL glutathione (a tripeptide containing a
cysteine residue) inhibition of Na+/K+-ATPase activity was blocked and an
increase in ATPase activity was observed. The presence of lipoxygenase enhanced
the inhibition of Na+/K+-ATPase activity caused by 20 ng/mL ouabain (31+/-2 vs.
19+/-2) but had little or no effect with higher concentrations of ouabain. These
findings suggest that lipoxygenase may regulate Na+/K+-ATPase by acting directly
on the enzyme.
PMID- 11007530
TI - The negative inotropic action of catecholamines: role of beta3-adrenoceptors.
AB - There is now evidence for the involvement of four beta-adrenoceptor populations
in the regulation of cardiac function by catecholamines. Beta1- and beta2
adrenoceptor stimulation classically produces an increase in contractility. A
fourth beta-adrenoceptor, as yet uncloned and designated provisionally as a beta4
adrenoceptor, also mediates a positive inotropic effect. Beta3-adrenoceptors,
which had been cloned at the end of the eighties, has been extensively studied as
a potential target for antiobesity and antidiabetic drugs. Its characterization
in the heart has opened new fields of investigations for the understanding of the
cardiac adrenergic regulation. This review describes the cardiac electrical and
mechanical effects induced by Beta3-adrenoceptor stimulation in different species
(including human), as well as the signaling pathway. It also analyzes the role of
these receptors in the abnormal responsiveness of catecholamines in heart
failure.
PMID- 11007532
TI - Tetraethylammonium-evoked oscillatory contractions of rat tail artery: a K-K
model.
AB - Spontaneously rhythmic contraction of peripheral blood vessels actively modulates
the peripheral circulation and blood pressure. However, the underlying mechanisms
for the complex rhythmic contraction patterns of various vascular tissues are not
yet fully understood. In the present study, the tetraethylammonium (TEA)-induced
spontaneously oscillatory contractions of isolated rat tail artery tissues were
examined. It was found that TEA evoked arterial oscillatory contractions in a
concentration-dependent, but endothelium-independent manner. The voltage
dependent K+ (Kv) channel specific blocker, 4-aminopyridine (4-AP), induced a
sustained, but not oscillated, vascular contraction. The presence of 4-AP had no
effect on the TEA-induced oscillatory contractions. The blockade of KCa channels
with charybdotoxin or apamin did not affect the basal force of vascular tissues.
Neither the TEA-induced oscillatory contraction was affected by these blockers.
The opening of KATP channels by levcromakalim or their blockade by glybenclamide
ceased or increased, respectively, the oscillation of TEA-induced contractions.
The absence of Ca2+ or the presence of nifedipine in the bath solution completely
abolished the effects of TEA. The inhibition of Ca2+-ATPase in the sarcoplasmic
reticulum with micromolar concentrations of thapsigargin or cyclopiazonic acid
either abolished or enhanced, respectively, the TEA-induced oscillatory
contractions. Ryanodine did not affect the TEA-induced oscillatory contraction.
In conclusion, the TEA-induced oscillatory contraction may be initiated by the
blockade of the TEA-sensitive delayed rectifier K+ channels and maintained by the
TEA-insensitive but ATP-sensitive K+ channels. This K-K model presents a novel
mechanism for the depolarization-induced rhythmic contractions of small arteries.
PMID- 11007533
TI - Selective potentiating effect of RS14203 on a serotoninergic pathway in
anesthetized rats.
AB - The usefulness of selective inhibitors of type 4 phosphodiesterase (PDE4) in the
treatment of inflammation and pulmonary diseases is limited by their side
effects: nausea and vomiting. We studied the effect of three structurally diverse
PDE4 inhibitors on the vagal nerve afferent and efferent fibers in anesthetized
rats. The effects of RS14203, (R)-rolipram, and CT-2450 were evaluated on the von
Bezold-Jarisch reflex (vagal afferent fibers) and in a model of vagal electrical
stimulation (vagal efferent fibers). All three PDE4 inhibitors were administered
at 1, 10, or 100 microg/kg (iv) 15 min prior to the induction of bradycardia by
an iv injection of 2-methyl-5-HT (von Bezold-Jarisch reflex) or by vagal
electrical stimulation. At 100 microg/kg, RS14203 significantly potentiated the 2
methyl-5-HT response. No statistically significant effects were observed with (R)
rolipram or CT-2450 at the doses studied. RS14203, (R)-rolipram, or CT-2450 (1
100 microg/kg iv) did not affect the bradycardia induced by vagal electrical
stimulation. Consequently, our results show that RS14203 selectively facilitates
serotoninergic neurotransmission in vagal afferent fibers. The emetic action of
RS14203 may be mediated by this mechanism.
PMID- 11007534
TI - Influence of T-type Ca2+ (mibefradil) and Cl- (indanyloxyacetic acid 94) channel
antagonists on alpha1-adrenoceptor mediated contractions in rat aorta.
AB - The effects of the T-type and L-type Ca2+ channel antagonists, mibefradil and
nifedipine, respectively, and those of a Cl- channel antagonist, indanyloxyacetic
acid 94, on mechanical responses elicited by selective activation of alpha1
adrenoceptors using cirazoline were examined in rat isolated aortic rings. The
presence of mibefradil (300 nM), indanyloxyacetic acid, 94 (30 microM) and
nifedipine (300 nM) alone inhibited mechanical responses elicited by cirazoline.
The concentration-response curves to cirazoline were displaced to the right with
significant increases in the EC50 and significant depressions of the maximal
responses in the presence of the individual agents mibefradil, indanyloxyacetic
acid 94, or nifedipine. A combination of mibefradil and indanyloxyacetic acid 94
further inhibited the mechanical activity produced by cirazoline. The further
reduction in the maximal response to cirazoline, in the presence of mibefradil
and nifedipine, was insignificant when compared with the effects of nifedipine
alone. In addition, maximal mechanical responses produced by cirazoline were not
significantly affected by a combination of nifedipine and indanyloxyacetic acid
94 when compared with either nifedipine alone or mibefradil and indanyloxyacetic
acid 94 combined. Our current findings indicate that mibefradil, indanyloxyacetic
acid 94, and nifedipine can inhibit cirazoline-induced contractions to a varying
degree. Moreover, based on our present data it would be reasonable to suggest
that the contribution of T-type versus L-type Ca2+ channels to contractile
responses obtained with cirazoline are approximately 21% and 35%, respectively,
of the Emax. It would appear that L-type Ca2+ channels play a greater role in
processes that are involved in excitation-contraction coupling subsequent to
stimulation of alpha1-adrenoceptors. In addition, Cl- channels also appear to be
involved in the process of contraction following alpha1-adrenoceptor activation.
PMID- 11007535
TI - Radiotelemetric monitoring of blood pressure and mesenteric arterial bed
responsiveness in rats with streptozotocin-induced diabetes.
AB - We investigated the changes in arterial blood pressure (BP) and of mesenteric
arterial bed (MAB) responsiveness that accompany streptozotocin (STZ)-induced
diabetes. BP was recorded by radiotelemetry in conscious animals before and
during a 4-week period following induction of the diabetic state with STZ. At the
end of this period, the MAB was isolated and perfused under constant flow
conditions: perfusion pressure (PP, mmHg) was taken as an index of arteriolar
tone. BP was lower (P < 0.05) in STZ-treated diabetic rats (82.9+/-5.0 mmHg) than
in vehicle-treated rats (108.9+/-6.3 mmHg). Basal perfusion pressure of the MAB
was lower in STZ-treated rats than in control rats and inhibition of nitric oxide
(NO) synthesis with N(G)-nitro-L-arginine-methyl-ester and N(G)-nitro-L-arginine
(100 microM each) failed to change this relationship. Increases in PP of MAB to
phenylephrine (Phe), norepinephrine (NE), and potassium chloride (KCl) were
reduced in STZ-treated rats compared with control rats. Inhibition of NO
synthesis reduced responses to Phe, NE, and KCL in both STZ and control rats. The
reduced responsiveness of STZ rats to Phe, NE, and KCl persisted after inhibition
of NO synthesis. Acetylcholine (ACh) evoked relaxation of the MAB in a dose
dependent fashion. Maximal responses to ACh, but not sodium nitroprusside, were
lower in STZ rats than in vehicle treated rats. Inhibition of NO synthesis
reduced responses to ACh in both STZ and control rats. The reduced responsiveness
of STZ rats to ACh persisted after inhibition of NO synthesis. The data
demonstrate that STZ-induced diabetes is associated with a fall in blood pressure
when pressure is recorded with radiotelemetry. The fall in blood pressure may be
related to a non-specific decrease in responsiveness to vasoconstrictor stimuli
mediated at least in part by NO-independent mechanisms. A decrease in
responsiveness to endothelial dependent vasodilator mechanisms appeared
insufficient to restore responsiveness to vasoconstrictor stimuli.
PMID- 11007536
TI - Activation of Rho signaling contributes to lysophosphatidic acid-induced
contraction of intact ileal smooth muscle of guinea-pig.
AB - To elucidate the possible role of Rho A/Rho-kinase on lysophosphatidic acid (LPA)
induced contraction in intact guinea-pig ileal smooth muscle, we examined effects
of pretreatment with a specific inhibitor of Rho-kinase (Y-27632) on the LPA
induced contraction and MLC20 phosphorylation. In addition, we investigated
whether LPA actually elicits an activation of Rho A by studying subcellular
distribution of Rho A in unstimulated and stimulated smooth muscles by LPA. LPA
induced a less intense, but sustained, contraction compared with ACh, and was
accompanied by significant increases in MLC20 phosphorylation. The effects of LPA
on tension and MLC20 phosphorylation were inhibited by Y-27632. The ACh-induced
contraction, but not increases in MLC20 phosphorylation, was partially inhibited
by Y-27632. High K+-induced contraction was unaffected by the inhibitor. LPA
stimulated translocation of Rho A from the cytosol to the membrane fraction of
the muscle. Translocation of Rho A was also induced by ACh and high K+. These
results suggest that LPA-induced contraction of intact ileal smooth muscle is
dominated through activation of Rho A and Rho-kinase and subsequent increases in
MLC20 phosphorylation.
PMID- 11007537
TI - Effect of stevioside on PAH transport by isolated perfused rabbit renal proximal
tubule.
AB - Stevioside, a non-caloric sweetening agent, is used as a sugar substitute. An
influence of stevioside on renal function has been suggested, but little is known
about its effect on tubular function. Therefore, the present study was designed
to explore the direct effect of stevioside on transepithelial transport of p
aminohippurate (PAH) in isolated S2 segments of rabbit proximal renal tubules
using in vitro microperfusion. Addition of stevioside at a concentration of 0.45
mM to either the tubular lumen, bathing medium, or both at the same time had no
effect on transepithelial transport of PAH. Similarly, a concentration of 0.70 mM
(maximum solubility in the buffer) when present in the lumen, had no effect on
PAH transport. However, this concentration in the bathing medium inhibited PAH
transport significantly by about 25-35%. The inhibitory effect of stevioside was
gradually abolished after it was removed from the bath. Addition of 0.70 mM
stevioside to both lumen and bathing medium at the same time produced no added
inhibitory effect. Stevioside at this concentration has no effect on Na+/K+
ATPase activity as well as cell ATP content. These findings suggest that
stevioside, at a pharmacological concentration of 0.70 mM, inhibits
transepithelial transport of PAH by interfering with the basolateral entry step,
the rate-limiting step for transepithelial transport. The lack of effect of
stevioside on transepithelial transport of PAH on the luminal side and its
reversible inhibitory effect on the basolateral side indicate that stevioside
does not permanently change PAH transport and should not harm renal tubular
function at normal human intake levels.
PMID- 11007538
TI - Inhibition of Ca2+-activated K+ channels by tyrosine phosphatase inhibitors in
rat mesenteric artery.
AB - To investigate the possible regulation of large-conductance Ca2+-activated K+
channels (BKCa) by tyrosine phosphatases (Tyr-PPs), single-channel currents of
myocytes from rat mesenteric artery were recorded in open cell-attached patches.
Two structurally different Tyr-PP inhibitors, sodium orthovanadate (Na3VO4) and
dephostatin, were used. The channels (236 pS) evoked at +40 mV and pCa 6, were
significantly inhibited by 1 mM Na3VO4 (-81+/-3%, n = 10; P < 0.005). Similarly,
100 microM dephostatin strongly inhibited the BKCa channels (-80+/-7%, n = 7 ; P
< 0.05). Therefore, BKCa channels in vascular smooth muscle cells may be
regulated by tyrosine phosphatase-dependent signal transduction pathways, whose
inhibition could attenuate the channel activity.
PMID- 11007539
TI - Block of inwardly rectifying K+ currents by extracellular Mg2+ and Ba2+ in bovine
pulmonary artery endothelial cells.
AB - Using whole-cell patch clamp technique, we investigated the blocking effects of
extracellular Ba2+ and Mg2+ on the inwardly rectifying K+ (KIR) currents of
bovine pulmonary artery endothelial cells (BPAEC). The BPAEC KIR channel has
recently been identified as Kir2.1 of the Kir2.0 subfamily. Block of KIR currents
by Mg2+ (3-30 mM) was instantaneous, and increased with hyperpolarization
slightly (Kd at -160 and 0 mV was 9.5 and 23.2 mM, respectively). The apparent
fractional electrical distance (delta) of the Mg2+ binding site is calculated to
be 0.07 from the outer mouth of the channel pore. Ba2+ (0.3-10 microM) time
dependently blocked the KIR currents with a much higher potency and stronger
voltage-dependence (Kd at -160 and 0 mV was 1.0 and 41.6 microM, respectively).
The Ba2+ binding site had a delta value of 0.34. Our data suggest that Mg2+ binds
to a very superficial site of the KIR channel, while Ba2+ binds to a much deeper
site, sensing much more of the membrane electric field. Thus, the BPAEC Kir2.1
appears to be pharmacologically different from the Kir2.1 reported before in
bovine aortic endothelial cells (BAEC), which has 2 sites for Mg2+ block (a deep
site in addition to a shallow one), and a superficial and low-sensitivity site
for Ba2+ block.
PMID- 11007540
TI - Variation in the vitreous phenotype of Stickler syndrome can be caused by
different amino acid substitutions in the X position of the type II collagen Gly
X-Y triple helix.
AB - Stickler syndrome is a dominantly inherited disorder characterized by
arthropathy, midline clefting, hearing loss, midfacial hypoplasia, myopia, and
retinal detachment. These features are highly variable both between and within
families. Mutations causing the disorder have been found in the COL2A1 and
COL11A1 genes. Premature termination codons in COL2A1 that result in
haploinsufficiency of type II collagen are a common finding. These produce a
characteristic congenital "membranous" anomaly of the vitreous of all affected
individuals. Experience has shown that vitreous slit-lamp biomicroscopy can
distinguish between patients with COL2A1 mutations and those with dominant
negative mutations in COL11A1, who produce a different "beaded" vitreous
phenotype. Here we characterize novel dominant negative mutations in COL2A1 that
result in Stickler syndrome. Both alter amino acids in the X position of the Gly
X-Y triple-helical region. A recurrent R365C mutation occurred in two unrelated
sporadic cases and resulted in the membranous vitreous anomaly associated with
haploinsufficiency. In a large family with linkage to COL2A1, with a LOD score of
2.8, a unique L467F mutation produced a novel "afibrillar" vitreous gel devoid of
all normal lamella structure. These data extend the mutation spectrum of the
COL2A1 gene and help explain the basis for the different vitreous phenotypes seen
in Stickler syndrome.
PMID- 11007542
TI - Dendritic mechanisms in brain function and developmental disabilities.
PMID- 11007541
TI - Small evolutionarily conserved RNA, resembling C/D box small nucleolar RNA, is
transcribed from PWCR1, a novel imprinted gene in the Prader-Willi deletion
region, which Is highly expressed in brain.
AB - Prader-Willi syndrome is a complex neurodevelopmental disorder caused by the
inactivation or deletion of imprinted, paternally expressed genes in chromosome
band 15q11.2. We report the identification and characterization of PWCR1, a novel
imprinted gene within that region, and its mouse orthologue, Pwcr1, which was
mapped to the conserved syntenic region on mouse chromosome 7. Expressed only
from the paternal allele, both genes require the imprinting-center regulatory
element for expression and are transcribed from the same strand. They are
intronless and do not appear to encode a protein product. High human/mouse
sequence similarity (87% identity) is limited to a 99-bp region called "HMCR"
(for "human-mouse conserved region"). The HMCR sequence has features of a C/D box
small nucleolar RNA (snoRNA) and is represented in an abundant small transcript
in both species. Located in nucleoli, snoRNAs serve as methylation guidance RNAs
in the modification of ribosomal RNA and other small nuclear RNAs. In addition to
the nonpolyadenylated small RNAs, larger polyadenylated PWCR1 transcripts are
found in most human tissues, whereas expression of any Pwcr1 RNAs is limited to
mouse brain. Genomic sequence analysis reveals the presence of multiple copies of
PWCR1 and Pwcr1 that are organized within local tandem-repeat clusters. On a
multispecies Southern blot, hybridization to an HMCR probe encoding the putative
snoRNA is limited to mammals.
PMID- 11007543
TI - Regulation of dendritic spine morphology by the rho family of small GTPases:
antagonistic roles of Rac and Rho.
AB - Dendritic spines mediate most excitatory transmission in the mammalian CNS and
have been traditionally considered stable structures. Following the suggestion
that spines may 'twitch', it has been recently shown that spines are capable of
rapid morphological rearrangements. Because of the role of the small GTPases from
the Rho family in controlling neuronal morphogenesis, we investigated the effects
of several members of this biochemical signaling pathway in the maintenance of
the morphology of extant dendritic spines by combining biolistic transfection of
pyramidal neurons in cultured cortical and hippocampal slices with two-photon
microscopy. We find a variety of effects on the density and morphology of
dendritic spines by expressing either constitutively active or dominant negative
forms of several small GTPases of the Rho family, by blocking the entire pathway
with Clostridium difficile toxin B or by blocking Rho with C3 transferase. We
propose a model where Rac promotes spine formation, while Rho prevents it. We
conclude that the small GTPases provide antagonistic control mechanisms of spine
maintenance in pyramidal neurons.
PMID- 11007544
TI - Thyroid hormone action in neural development.
AB - Effects of thyroid hormone on development of the brain have been documented for
over a century. Although in many respects the hypothyroid brain appears
morphologically normal, functional impairments include mental retardation, ataxia
and spasticity. Keyed by the discovery of nuclear receptors for thyroid hormone
that function as transcription factors, recent work has examined the mechanism of
thyroid hormone action in brain development. The prediction that gene expression
regulated by thyroid hormone is important for mediating brain development has
spurred the search for thyroid hormone-responsive genes. Here we review some of
the identified genes whose expression patterns correlate with the functional
deficits observed in the hypothyroid brain. Recently identified thyroid hormone
responsive genes include synaptotagmin-related gene 1 (Srg1), a putative mediator
of synaptic structure and/or activity, and hairless, a transcriptional cofactor
that may influence the expression of other thyroid hormone-responsive genes.
PMID- 11007545
TI - Role of afferent innervation and neuronal activity in dendritic development and
spine maturation of fascia dentata granule cells.
AB - By using slice cultures of hippocampus as a model, we have studied the
development of dendritic spines in fascia dentata granule cells. We raised the
question as to what extent spine development is dependent on a major afferent
input to these neurons, the fibers from the entorhinal cortex and neuronal
activity mediated by these axons. Our results can be summarized as follows: (i)
the entorhino-hippocampal projection develops in an organotypic manner in co
cultures of entorhinal cortex and hippocampus. Like in vivo, entorhinal fibers,
labeled by anterograde tracing with biocytin, terminate in the outer molecular
layer of the fascia dentata. (ii) The layer-specific termination of entorhinal
fibers is not altered by the blockade of neuronal activity with tetrodotoxin.
Likewise, the differentiation of the dendritic arbor of postsynaptic granule
cells does not require neuronal activity. Blockade of neuronal activity did not
affect the mean spine number of granule cell dendrites in entorhino-hippocampal
co-cultures, but led to a relative increase in thin, long filiform spines that
are characteristic of immature neurons. (iii) The maturation of the granule cell
dendritic arbor is, however, controlled by the afferent fibers from the
entorhinal cortex in an activity-independent manner. In single slice cultures of
hippocampus lacking entorhinal input, Golgi-impregnated granule cells have much
shorter, less branched dendrites when compared with granule cells in entorhino
hippocampal co-cultures. This reduction in dendritic length in granule cells
lacking entorhinal input results in a lower mean total number of spines per
neuron, but the mean number of spines per microm is not reduced in the absence of
entorhinal innervation. These results indicate that innervation by fibers from
the entorhinal cortex, but not neuronal activity mediated via these axons, is
essential for the normal development of the granule cell dendritic arbor.
Neuronal activity is required, however, for the maturation of dendritic spines.
PMID- 11007546
TI - Structural synaptic modifications associated with hippocampal LTP and behavioral
learning.
AB - An important problem in the neurobiology of memory is whether cellular mechanisms
of learning and memory include the formation of new synapses or the remodeling of
existing ones. To elucidate this problem, numerous studies have examined
alterations in the number and structure of synapses following behavioral learning
and hippocampal long-term potentiation (LTP), which is viewed as a synaptic model
of memory. The data reported in the literature and obtained in this laboratory
are analyzed here to evaluate what kind of structural modification is likely to
account for synaptic plasticity associated with learning and memory. It has been
demonstrated that LTP induction elicits the formation of additional synapses
between activated axon terminals and newly emerging dendritic spines. Similarly,
some forms of learning have been shown to increase the number of synapses.
Although many ultrastructural studies examining the effect of LTP or learning
failed to find a change in total synapse number, this population measure might
not detect an increase in a small proportion of synapses established by activated
terminals. LTP and learning have also been shown to induce a remodeling of
synapses. This process is proposed to involve the transformation of certain
synaptic subtypes into more efficacious ones, including the conversion of
'silent' synapses into functional synapses. It appears, therefore, that cellular
mechanisms of learning and memory are likely to include both synaptogenesis and
synapse remodeling.
PMID- 11007547
TI - Cellular and molecular mechanisms of dendrite growth.
AB - Proper growth and branching of dendrites are crucial for nervous system function;
patterns of dendritic arborization determine the nature and amount of innervation
that a neuron receives and specific dendritic membrane properties define its
computational capabilities. Until recently, there was relatively little known
about the cellular and molecular mechanisms of dendritic growth, perhaps because
dendrites were historically considered to be intrinsically determined, passive
elements in the formation of connections in the nervous system. In the last few
years, however, overwhelming evidence has accumulated indicating that dendritic
growth is remarkably dynamic and responsive to environmental signals, including
guidance molecules and levels and patterns of activity. This manuscript reviews
our current understanding of the cellular and molecular mechanisms of dendritic
growth, the influence of activity in sculpting specific patterns of dendritic
arbors, and a potential integral role for dendrites in activity-dependent
development of circuits in the nervous system.
PMID- 11007548
TI - Serotonin induces EPSCs preferentially in layer V pyramidal neurons of the
frontal cortex in the rat.
AB - The effect of serotonin (5-HT) on the release of glutamate was examined in
pyramidal cells in layers II-VI of the frontal cortex. The intracellular
recording electrode contained 1% biocytin so the neurons could later be
visualized with an avidin-biotin peroxidase method. Pyramidal cells in layer V of
the frontal cortex showed the greatest 5-HT-induced increase in both the
frequency and amplitude of 'spontaneous' (non-electrically evoked) excitatory
post-synaptic currents (EPSCs). A small proportion of neurons in layer II/III
showed an increase in EPSC frequency, whereas cells in layer VI showed no
significant change in either EPSC frequency or amplitude. The physiological
response to 5-HT mirrors the high density of 5-HT(2A) receptors in layer V, as
well as the pattern of thalamic projections in frontal cortex. The specific
induction of EPSCs in layer V neurons suggests that 5-HT preferentially modulates
the output neurons of the frontal cortex.
PMID- 11007549
TI - Dendritic anomalies in disorders associated with mental retardation.
AB - Dendritic abnormalities are the most consistent anatomical correlates of mental
retardation (MR). Earliest descriptions included dendritic spine dysgenesis,
which was first associated with unclassified MR, but can also be found in genetic
syndromes associated with MR. Genetic disorders with well-defined dendritic
anomalies involving branches and/or spines include Down, Rett and fragile-X
syndromes. Cytoarchitectonic analyses also suggest dendritic pathology in
Williams and Rubinstein-Taybi syndromes. Dendritic abnormalities appear to have
syndrome-specific pathogenesis and evolution, which correlate to some extent with
their cognitive profile. The significance of dendritic pathology in synaptic
circuitry and the role of animal models in the study of MR-associated dendritic
abnormalities are also discussed. Finally, a model of genotype to neurologic
phenotype pathway in MR, centered in dendritic abnormalities, is postulated.
PMID- 11007550
TI - Dendritic cytoskeletal protein expression in mental retardation: an
immunohistochemical study of the neocortex in Rett syndrome.
AB - Many syndromes associated with mental retardation (MR) are characterized by
cortical dendritic anomalies. Despite their morphological similarity, these
changes appear to involve different stages of dendritic development. The neuronal
cytoskeleton, which includes microfilaments, neurofilaments and microtubules, is
essential for these developmental processes. Levels and phosphorylation of
microtubule-associated proteins (MAPs), which stabilize microtubules, seem to
determine different stages of dendritic formation with certain MAPs (e.g. MAP-2)
appearing to mediate the effects of external modulators upon these processes.
Early studies on neuronal cytoskeleton in MR, which have shown a selective
reduction in MAP-2 expression, have focused on Rett syndrome (RS). Here, by a
semiquantitative immunohistochemical analysis of the pericentral cortex, we
examine the contribution of specific neuronal populations to these changes in
cytoskeletal proteins. Decreased MAP-2 staining in RS was more marked in layers V
VI, while increased nonphosphorylated neurofilament immunoreactivity was found in
layers II-III in RS. Age-related increases in dendritic MAP-2 immunoreactivity in
layers V-VI were also absent in RS. The specificity of these cytoskeletal protein
changes, their significance for RS pathogenesis and plasticity, as well as their
implications for other MR-associated disorders, are also discussed.
PMID- 11007551
TI - Connectivity of ectopic neurons in the molecular layer of the somatosensory
cortex in autoimmune mice.
AB - Approximately 50% of New Zealand Black mice (NZB/BINJ) and 80% of NXSM-D/EiJ mice
prenatally develop neocortical layer I ectopias, mostly in somatosensory
cortices. These cortical anomalies are similar to those seen in the brains of
individuals with dyslexia. Neurofilament staining revealed a radial column of
tightly packed fiber bundles in the layers underlying ectopias. This suggested
that the connectivity of the ectopic neurons was aberrant. The present study used
the tracers 1,1'-dioctadecyl- 3,3,3',3'-tetramethylindo- carbocyanine perchlorate
(DiI) and biotinylated dextran amine (BDA) to more thoroughly explore the
cortical and thalamic connectivity of the ectopias. DiI placement into ectopias
again revealed a distinct bundle of fibers extending from the ectopic neurons to
the deep cortical layers. This bundle split in the white matter with some fibers
traveling to the corpus callosum and others to the internal capsule. Thalamic
connections were concentrated in the ventrobasal com- plex (VB) and posterior
thalamic nucleus group (Po). Injections of BDA into VB revealed reciprocal
connections between VB and the ectopic cortical neurons. Ipsilateral
corticocortical projections were seen between ectopias in primary somatosensory
and motor and secondary somatosensory cortices, but no contralateral connections
of the ectopic neurons were seen. These findings confirm the notion that layer I
ectopias are anomalously connected by comparison to neurons in homologous cortex,
which may underlie widespread dysfunction of brains containing ectopias.
PMID- 11007552
TI - Convergence and plasticity of monoaminergic systems in the medial prefrontal
cortex during the postnatal period: implications for the development of
psychopathology.
AB - A variety of observations have suggested that the dopamine and serotonin systems
may play a role in the pathophysiology and treatment of major mental disorders of
childhood, adolescence and early adulthood. A recent triple immunofluorescence
study has demonstrated a convergence of serotonin and dopamine fibers onto both
pyramidal cells and GABAergic interneurons in the rat medial prefrontal cortex
(mPFCx). These findings are consistent with the results of an
electrophysiological study conducted in another laboratory that suggested such a
relationship exists in the pyriform cortex of the rodent brain. During postnatal
development, the dopamine system shows a progressive ingrowth of fibers into this
region that continues until the early adult period. In contrast, GABAergic
neurons appear to complete their postnatal maturation by the fourth postnatal
week (the early post-weanling period). As dopamine fibers infiltrate the rat
mPFCx, they progressively increase their interaction with neural elements within
the neuropil and with the cell bodies of both pyramidal cells and GABAergic
interneurons. This process appears to be influenced by the serotonin system,
since lesioning of the nucleus raphe dorsalis during the neonatal period results
in a significant increase of dopamine fibers. This finding suggests that lesions
of the serotonin system induce plasticity of the cortical dopamine system;
however, it is not known whether this inferred suppressive effect of serotonin
fibers occurs at brainstem levels or within the mPFCx itself. Taken together,
these various studies suggest that the convergence of dopamine and serotonin
fiber systems on intrinsic cortical neurons shows considerable plasticity during
postnatal life that could theoretically contribute to the development of
'miswired' circuits in individuals with neuropsychiatric disorders.
PMID- 11007553
TI - Gangliosides as modulators of dendritogenesis in normal and storage disease
affected pyramidal neurons.
AB - Pyramidal cells initiate the formation of dendritic arbors in a prolific burst of
neurite outgrowth during early cortical development. Although morphologically
mature pyramidal neurons do not normally sprout additional primary dendrites, the
discovery of ectopic dendritogenesis in neuronal storage diseases has revealed
that these cells do retain this ability under appropriate stimulation. The
capacity for renewal of dendritogenesis has been found to exhibit a species
gradient with human > cat, dog, sheep > mouse. A consistent metabolic feature of
ectopic dendrite-bearing pyramidal neurons is a heightened intracellular
expression of GM2 ganglioside. Elevated expression of this same glycosphingolipid
has also been found to correlate with normal dendritogenesis. Immature neurons in
developing cat and ferret cortex exhibit high levels of GM2 ganglioside
immunoreactivity coincident with normal dendritic sprouting and a similar
relationship has now been shown for human cortical development. Ultrastructural
studies of all three species revealed GM2 localized to vesicles in a manner
consistent with Golgi synthesis and exocytic trafficking to the somatic-dendritic
plasmalemma. We propose that GM2 ganglioside functions in glycosphingolipid
enriched microdomains (lipid rafts) in the plasmalemma to promote dendritic
initiation through modulation of specific membrane proteins and/or their
associated second messenger cascades.
PMID- 11007554
TI - Dendritic spine structural anomalies in fragile-X mental retardation syndrome.
AB - Fragile-X syndrome is the most common single-gene inherited form of mental
retardation. Morphological studies suggest a possible failure of the synapse
maturation process. Cerebral cortical spine morphology in fragile-X syndrome and
in a knockout mouse model of it appears immature, with long, thin spines much
more common than the stubby and mushroom-shaped spines more characteristic of
normal development. In human fragile-X syndrome there is also a higher density of
spines along dendrites, suggesting a possible failure of synapse elimination.
While variously misshapen spines are characteristic of a number of mental
retardation syndromes, the overabundance of spines seen in fragile-X syndrome is
unusual. Taken with evidence of neurotransmitter activation of the synthesis of
the fragile-X protein (FMRP) at synapses in vitro and evidence for behaviorally
induced FMRP expression in vivo, and with evidence compatible with a role for
FMRP in regulating the synthesis of other proteins, it is possible that FMRP
serves as an 'immediate early protein' at the synapse that orchestrates aspects
of synaptic development and plasticity.
PMID- 11007555
TI - FMRP involvement in formation of synapses among cultured hippocampal neurons.
AB - Fragile-X, the main cause of inherited human mental retardation is associated
with the absence of a recently identified fragile-X mental retardation protein
(FMRP). Mice in which this protein is lacking due to a knockout (KO) mutation are
reported to express altered dendritic spines on their cortical neurons compared
with wild type (WT) controls. We have used tissue-cultured neurons to examine
differences in morphology and synaptic connectivity between WT and FMRP-deficient
mice. Hippocampal neurons taken from KO mice and grown in culture for 3 weeks
have shorter dendrites and fewer dendritic spines than their WT counterparts.
Also, KO cells tend to express fewer functional synaptic connections, which
develop more slowly and produce smaller excitatory synaptic currents than WT
controls. These observations may have important implications for the
understanding of mental retardation associated with the absence of FMRP.
PMID- 11007556
TI - Highlighted topics series: cellular responses to mechanical stress.
PMID- 11007557
TI - Beta-adrenergic agonist therapy accelerates the resolution of hydrostatic
pulmonary edema in sheep and rats.
AB - To determine whether beta-adrenergic agonist therapy increases alveolar liquid
clearance during the resolution phase of hydrostatic pulmonary edema, we studied
alveolar and lung liquid clearance in two animal models of hydrostatic pulmonary
edema. Hydrostatic pulmonary edema was induced in sheep by acutely elevating left
atrial pressure to 25 cmH(2)O and instilling 6 ml/kg body wt isotonic 5% albumin
(prepared from bovine albumin) in normal saline into the distal air spaces of
each lung. After 1 h, sheep were treated with a nebulized beta-agonist
(salmeterol) or nebulized saline (controls), and left atrial pressure was then
returned to normal. beta-Agonist therapy resulted in a 60% increase in alveolar
liquid clearance over 3 h (P < 0.001). Because the rate of alveolar fluid
clearance in rats is closer to human rates, we studied beta-agonist therapy in
rats, with hydrostatic pulmonary edema induced by volume overload (40% body wt
infusion of Ringer lactate). beta-Agonist therapy resulted in a significant
decrease in excess lung water (P < 0.01) and significant improvement in arterial
blood gases by 2 h (P < 0.03). These preclinical experimental studies support the
need for controlled clinical trials to determine whether beta-adrenergic agonist
therapy would be of value in accelerating the resolution of hydrostatic pulmonary
edema in patients.
PMID- 11007558
TI - Increased spinal monoamine concentrations after chronic thoracic dorsal rhizotomy
in goats.
AB - In goats, bilateral thoracic dorsal rhizotomy (TDR) causes severe ventilatory
failure during exercise, followed by progressive functional recovery. We
investigated spinal neurochemical changes associated with TDR and/or functional
recovery by measuring spinal concentrations of the monoamines serotonin (5-HT),
norepinephrine, and dopamine via HPLC. Changes in 5-HT and calcitonin gene
related peptide were visualized with immunohistochemistry. Goat spinal cords were
compared 4-15 mo after TDR from T(2) to T(12) (n = 7) with sham-operated (n = 4)
or unoperated controls (n = 4). TDR increased the concentration of cervical 5-HT
(C(5)-C(6); 122% change), caudal thoracic norepinephrine (T(7)-T(11); 53%
change), and rostral thoracic dopamine (T(3)-T(6); 234% change). TDR increased 5
HT-immunoreactive terminal density (dorsal and ventral horns) and nearly
eliminated calcitonin gene-related peptide immunoreactivity in the superficial
laminae of the dorsal horn in rostral thoracic segments; both effects became less
pronounced in caudal thoracic segments. Thus TDR elevates monoamine
concentrations in discrete spinal regions, including possible compensatory
changes in descending serotonergic inputs to spinal segments not directly
affected by TDR (i.e., cervical) but associated with functionally related motor
nuclei (i.e., phrenic nucleus).
PMID- 11007559
TI - Upper airway muscle responsiveness to rising PCO(2) during NREM sleep.
AB - Although pharyngeal muscles respond robustly to increasing PCO(2) during
wakefulness, the effect of hypercapnia on upper airway muscle activation during
sleep has not been carefully assessed. This may be important, because it has been
hypothesized that CO(2)-driven muscle activation may importantly stabilize the
upper airway during stages 3 and 4 sleep. To test this hypothesis, we measured
ventilation, airway resistance, genioglossus (GG) and tensor palatini (TP)
electromyogram (EMG), plus end-tidal PCO(2) (PET(CO(2))) in 18 subjects during
wakefulness, stage 2, and slow-wave sleep (SWS). Responses of ventilation and
muscle EMG to administered CO(2) (PET(CO(2)) = 6 Torr above the eupneic level)
were also assessed during SWS (n = 9) or stage 2 sleep (n = 7). PET(CO(2))
increased spontaneously by 0.8 +/- 0.1 Torr from stage 2 to SWS (from 43.3 +/-
0.6 to 44.1 +/- 0.5 Torr, P < 0.05), with no significant change in GG or TP EMG.
Despite a significant increase in minute ventilation with induced hypercapnia
(from 8.3 +/- 0.1 to 11.9 +/- 0.3 l/min in stage 2 and 8.6 +/- 0.4 to 12.7 +/-
0.4 l/min in SWS, P < 0.05 for both), there was no significant change in the GG
or TP EMG. These data indicate that supraphysiological levels of PET(CO(2)) (50.4
+/- 1.6 Torr in stage 2, and 50.4 +/- 0.9 Torr in SWS) are not a major
independent stimulus to pharyngeal dilator muscle activation during either SWS or
stage 2 sleep. Thus hypercapnia-induced pharyngeal dilator muscle activation
alone is unlikely to explain the paucity of sleep-disordered breathing events
during SWS.
PMID- 11007560
TI - Altered airway surfactant phospholipid composition and reduced lung function in
asthma.
AB - Pulmonary surfactant in bronchoalveolar lavage fluid (BALF) and induced sputum
from adults with stable asthma (n = 36) and healthy controls (n = 12) was
analyzed for phospholipid and protein compositions and function. Asthmatic
subjects were graded as mild, moderate, or severe. Phospholipid compositions of
BALF and sputum from control subjects were similar and characteristic of
surfactant. For asthmatic subjects, the proportion of dipalmitoyl
phosphatidylcholine (16:0/16:0PC), the major phospholipid in surfactant,
decreased in sputum (P < 0.05) but not in BALF. In BALF, mole percent 16:0/16:0PC
correlated with surfactant function measured in a capillary surfactometer, and
sputum mole percent 16:0/16:0PC correlated with lung function (forced expiratory
volume in 1 s). Neither surfactant protein A nor total protein concentration in
either BALF or sputum was altered in asthma. These results suggest altered
phospholipid composition and function of airway (sputum) but not alveolar (BALF)
surfactant in stable asthma. Such underlying surfactant dysfunction may
predispose asthmatic subjects to further surfactant inhibition by proteins or
aeroallergens in acute asthma episodes and contribute to airway closure in
asthma. Consequently, administration of an appropriate therapeutic surfactant
could provide clinical benefit in asthma.
PMID- 11007562
TI - Postexercise rehydration: effect of Na(+) and volume on restoration of fluid
spaces and cardiovascular function.
AB - Our purpose was to study the interaction between Na(+) content and fluid volume
on rehydration (RH) and restoration of fluid spaces and cardiovascular (CV)
function. Ten men completed four trials in which they exercised in a 35 degrees C
environment until dehydrated by 2. 9% body mass, were rehydrated for 180 min, and
exercised for an additional 20 min. Four RH regimens were tested: low volume
(100% fluid replacement)-low (25 mM) Na(+) (LL), low volume-high (50 mM) Na(+)
(LH), high volume (150% fluid replacement)-low Na(+) (HL), and high volume-high
Na(+) (HH). Blood and urine samples were collected and body mass was measured
before and after exercise and every hour during RH. Before and after the
dehydration exercise and during the 20 min of exercise after RH, cardiac output
was measured. Fluid compartment (intracellular and extracellular) restoration and
percent change in plasma volume were calculated using the Cl(-) and hematocrit/Hb
methods, respectively. RH was greater (P < 0.05) in HL and HH (102.0 +/- 15.2 and
103.7 +/- 14.7%, respectively) than in LL and LH (70.7 +/- 10.5 and 75.9 +/-
6.3%, respectively). Intracellular RH was greater in HL (1.12 +/- 0.4 liters)
than in all other conditions (0.83 +/- 0.3, 0.69 +/- 0.2, and 0.73 +/- 0.3 liter
for LL, LH, and HH, respectively), whereas extracellular RH (including plasma
volume) was greater in HL and HH (1.35 +/- 0.8 and 1.63 +/- 0.4 liters,
respectively) than in LL and LH (0.83 +/- 0.3 and 1.05 +/- 0.4 liters,
respectively). CV function (based on stroke volume, heart rate, and cardiac
output) was restored equally in all conditions. These data indicate that greater
RH can be achieved through larger volumes of fluid and is not affected by Na(+)
content within the range tested. Higher Na(+) content favors extracellular fluid
filling, whereas intracellular fluid benefits from higher volumes of fluid with
lower Na(+). Alterations in Na(+) and/or volume within the range tested do not
affect the degree of restoration of CV function.
PMID- 11007561
TI - Role of convective O(2) delivery in determining VO(2) on-kinetics in canine
muscle contracting at peak VO(2).
AB - A previous study (Grassi B, Gladden LB, Samaja M, Stary CM, and Hogan MC, J Appl
Physiol 85: 1394-1403, 1998) showed that convective O(2) delivery to muscle did
not limit O(2) uptake (VO(2)) on-kinetics during transitions from rest to
contractions at approximately 60% of peak VO(2). The present study aimed to
determine whether this finding is also true for transitions involving
contractions of higher metabolic intensities. VO(2) on-kinetics were determined
in isolated canine gastrocnemius muscles in situ (n = 5) during transitions from
rest to 4 min of electrically stimulated isometric tetanic contractions
corresponding to the muscle peak VO(2). Two conditions were compared: 1)
spontaneous adjustment of muscle blood flow (Q) (Control) and 2) pump-perfused Q,
adjusted approximately 15-30 s before contractions at a constant level
corresponding to the steady-state value during contractions in Control (Fast O(2)
Delivery). In Fast O(2) Delivery, adenosine was infused intra-arterially. Q was
measured continuously in the popliteal vein; arterial and popliteal venous O(2)
contents were measured at rest and at 5- to 7-s intervals during the transition.
Muscle VO(2) was determined as Q times the arteriovenous blood O(2) content
difference. The time to reach 63% of the VO(2) difference between resting
baseline and steady-state values during contractions was 24.9 +/- 1.6 (SE) s in
Control and 18.5 +/- 1.8 s in Fast O(2) Delivery (P < 0.05). Faster VO(2) on
kinetics in Fast O(2) Delivery was associated with an approximately 30% reduction
in the calculated O(2) deficit and with less muscle fatigue. During transitions
involving contractions at peak VO(2), convective O(2) delivery to muscle,
together with an inertia of oxidative metabolism, contributes in determining the
VO(2) on-kinetics.
PMID- 11007563
TI - Differences in airway structure in immature and mature rabbits.
AB - Our laboratory has previously demonstrated that maximal bronchoconstriction
produces a greater degree of airway narrowing in immature than in mature rabbit
lungs (33). To determine whether these maturational differences could be related
to airway structure, we compared the fraction of the airway wall occupied by
airway smooth muscle (ASM) and cartilage, the proportion of wall area internal to
ASM, and the number of alveolar attachments to the airways, from mature and
immature (6-mo- and 4-wk-old, respectively) rabbit lungs that were formalin fixed
at total lung capacity. The results demonstrate that the airway walls of immature
rabbits had a greater percentage of smooth muscle, a lower percentage of
cartilage, and fewer alveolar attachments compared with mature rabbit airways;
however, we did not find maturational differences in the airway wall thickness
relative to airway size. We conclude that structural differences in the airway
wall may contribute to the greater airway narrowing observed in immature rabbits
during bronchoconstriction.
PMID- 11007564
TI - Venoarterial CO(2) difference during regional ischemic or hypoxic hypoxia.
AB - To test the role of blood flow in tissue hypoxia-related increased veno-arterial
PCO(2) difference (DeltaPCO(2)), we decreased O(2) delivery (&Ddot;O(2)) by
either decreasing flow [ischemic hypoxia (IH)] or arterial PO(2) [hypoxic hypoxia
(HH)] in an in situ, vascularly isolated, innervated dog hindlimb perfused with a
pump-membrane oxygenator system. Twelve anesthetized and ventilated dogs were
studied, with systemic hemodynamics maintained within normal range. In the IH
group (n = 6), hindlimb DO(2) was progressively lowered every 15 min by
decreasing pump-controlled flow from 60 to 10 ml. kg(-1). min(-1), with arterial
PO(2) constant at 100 Torr. In the HH group (n = 6), hindlimb DO(2) was
progressively lowered every 15 min by decreasing PO(2) from 100 to 15 Torr, when
flow was constant at 60 ml. kg(-1). min(-1). Limb DO(2), O(2) uptake (VO(2)), and
DeltaPCO(2) were obtained every 15 min. Below the critical DO(2), VO(2)
decreased, indicating dysoxia, and O(2) extraction ratio (VO(2)/DO(2)) rose
continuously and similarly in both groups, reaching a maximal value of
approximately 90%. DeltaPCO(2) significantly increased in IH but never differed
from baseline in HH. We conclude that absence of increased DeltaPCO(2) does not
preclude the presence of tissue dysoxia and that decreased flow is a major
determinant in increased DeltaPCO(2).
PMID- 11007565
TI - A predictive model of fatigue in human skeletal muscles.
AB - Fatigue is a major limitation to the clinical application of functional
electrical stimulation. The activation pattern used during electrical stimulation
affects force and fatigue. Identifying the activation pattern that produces the
greatest force and least fatigue for each patient is, therefore, of great
importance. Mathematical models that predict muscle forces and fatigue produced
by a wide range of stimulation patterns would facilitate the search for optimal
patterns. Previously, we developed a mathematical isometric force model that
successfully identified the stimulation patterns that produced the greatest
forces from healthy subjects under nonfatigue and fatigue conditions. The present
study introduces a four-parameter fatigue model, coupled with the force model
that predicts the fatigue induced by different stimulation patterns on different
days during isometric contractions. This fatigue model accounted for 90% of the
variability in forces produced by different fatigue tests. The predicted forces
at the end of fatigue testing differed from those observed by only 9%. This model
demonstrates the potential for predicting muscle fatigue in response to a wide
range of stimulation patterns.
PMID- 11007566
TI - Neurocirculatory consequences of intermittent asphyxia in humans.
AB - We examined the neurocirculatory and ventilatory responses to intermittent
asphyxia (arterial O(2) saturation = 79-85%, end-tidal PCO(2) =3-5 Torr above
eupnea) in seven healthy humans during wakefulness. The intermittent asphyxia
intervention consisted of 20-s asphyxic exposures alternating with 40-s periods
of room-air breathing for a total of 20 min. Minute ventilation increased during
the intermittent asphyxia period (14.2 +/- 2.0 l/min in the final 5 min of
asphyxia vs. 7.5 +/- 0.4 l/min in baseline) but returned to the baseline level
within 2 min after completion of the series of asphyxic exposures. Muscle
sympathetic nerve activity increased progressively, reaching 175 +/- 12% of
baseline in the final 5 min of the intervention. Unlike ventilation, sympathetic
activity remained elevated for at least 20 min after removal of the chemical
stimuli (150 +/- 10% of baseline in the last 5 min of the recovery period).
Intermittent asphyxia caused a small, but statistically significant, increase in
heart rate (64 +/- 4 beats/min in the final 5 min of asphyxia vs. 61 +/- 4
beats/min in baseline); however, this increase was not sustained after the return
to room-air breathing. These data demonstrate that relatively short-term exposure
to intermittent asphyxia causes sympathetic activation that persists after
removal of the chemical stimuli. This carryover effect provides a potential
mechanism whereby intermittent asphyxia during sleep could lead to chronic
sympathetic activation in patients with sleep apnea syndrome.
PMID- 11007567
TI - Effects of beta-hydroxy-beta-methylbutyrate on muscle damage after a prolonged
run.
AB - This study examined the effects of supplemental beta-hydroxy-beta-methylbutyrate
(HMB) on muscle damage as a result of intense endurance exercise. Subjects (n =
13) were paired according to their 2-mile run times and past running experience.
Each pair was randomly assigned a treatment of either HMB (3 g/day) or a placebo.
After 6 wk of daily training and supplementation, all subjects participated in a
prolonged run (20-km course). Creatine phosphokinase and lactate dehydrogenase
(LDH) activities were measured before and after a prolonged run to assess muscle
damage. The placebo-supplemented group exhibited a significantly greater
(treatment main effect, P = 0.05) increase in creatine phosphokinase activity
after a prolonged run than did the HMB-supplemented group. In addition, LDH
activity was significantly lower (treatment main effect, P = 0.003) with HMB
supplementation compared with the placebo-supplemented group. In conclusion,
supplementation with 3.0 g of HMB results in a decreased creatine phosphokinase
and LDH response after a prolonged run. These findings support the hypothesis
that HMB supplementation helps prevent exercise-induced muscle damage.
PMID- 11007568
TI - No evidence for long-term facilitation after episodic hypoxia in spontaneously
breathing, anesthetized rats.
AB - Repeated electrical or hypoxic stimulation of peripheral chemoreceptors has been
shown to cause a persistent poststimulus increase in respiratory motoneuron
activity, termed long-term facilitation (LTF). LTF after episodic hypoxia has
been demonstrated most consistently in anesthetized, vagotomized, paralyzed,
artificially ventilated rats. Evidence for LTF in spontaneously breathing animals
and humans after episodic hypoxia is equivocal and may have been influenced by
the awake state of the subjects in these studies. The present study was designed
to test the hypothesis that LTF is evoked in respiratory-related tongue muscle
and inspiratory pump muscle activities after episodic hypoxia in 10 spontaneously
breathing, anesthetized, vagotomized rats. The animals were exposed to three (5
min) episodes of isocapnic hypoxia, separated by 5 min of hyperoxia (50% inspired
oxygen). Genioglossus, hyoglossus, and inspiratory intercostal EMG activities,
along with respiratory-related tongue movements and esophageal pressure, were
recorded before, during, and for 60 min after the end of episodic isocapnic
hypoxia. We found no evidence for LTF in tongue muscle (genioglossus, hyoglossus)
or inspiratory pump muscle (inspiratory intercostal) activities after episodic
hypoxia. Rather, the primary poststimulus effect of episodic hypoxia was
diminished respiratory frequency, which contributed to a reduction in ventilatory
drive.
PMID- 11007569
TI - Dynamic viscoelastic behavior of lower extremity tendons during simulated
running.
AB - The aim of this project was to see whether the tendon would show creep during
long-term dynamic loading (here referred to as dynamic creep). Pig tendons were
loaded by a material-testing machine with a human Achilles tendon force profile
(1.37 Hz, 3% strain, 1,600 cycles), which was obtained in an earlier in vivo
experiment during running. All the pig tendons showed some dynamic creep during
cyclic loading (between 0.23 +/- 0.15 and 0.42 +/- 0.21%, means +/- SD). The pig
tendon data were used as an input of a model to predict dynamic creep in the
human Achilles tendon during running of a marathon and to evaluate whether there
might consequently be an influence on group Ia afferent-mediated length and
velocity feedback from muscle spindles. The predicted dynamic creep in the
Achilles tendon was considered to be too small to have a significant influence on
the length and velocity feedback from soleus during running. In spite of the
characteristic nonlinear viscoelastic behavior of tendons, our results
demonstrate that these properties have a minor effect on the ability of tendons
to act as predictable, stable, and elastic force transmitters during long-term
cyclic loading.
PMID- 11007570
TI - Differential effects of furosemide on porcine bronchial arterial and airway
smooth muscle.
AB - Furosemide attenuates airway obstruction in asthmatic subjects when administered
as an aerosol pretreatment. This protective effect of furosemide could be related
to relaxation of bronchial smooth muscle or to increased bronchial blood flow. To
determine whether furosemide dilates bronchial smooth muscle, isometric
contractile responses in distal bronchi from young pigs were studied. In
bronchial smooth muscle rings that were precontracted with 10(-5) M
acetylcholine, significant relaxation occurred with 10(-8) to 3 x 10(-6) M
isoproterenol but not with 10(-8) to 10(-3) M furosemide. In contrast, bronchial
arteries that were precontracted with either 10(-4) M norepinephrine or 10(-8) M
vasopressin significantly relaxed in response to 10(-4) to 3 x 10(-3) M and 10(
3) to 3 x 10(-3) M furosemide, respectively. We conclude that furosemide, under
the described experimental conditions, relaxes airway vascular smooth muscle but
not bronchial smooth muscle. These results are consistent with previous
suggestions that inhaled furosemide increases blood flow to airway tissues
(Gilbert IA, Lenner KA, Nelson JA, Wolin AD, and Fouke JM. J Appl Physiol 76: 409
415, 1994).
PMID- 11007571
TI - IGF-I restores satellite cell proliferative potential in immobilized old skeletal
muscle.
AB - One of the key factors responsible for the age-associated reduction in muscle
mass may be that satellite cell proliferation potential (number of doublings
contained within each cell) could become rate limiting to old muscle regrowth. No
studies have tested whether repeated cycles of atrophy-regrowth in aged animals
deplete the remaining capacity of satellite cells to replicate or what measures
can be taken to prevent this from happening. We hypothesized that there would be
a pronounced loss of satellite cell proliferative potential in gastrocnemius
muscles of aged rats (25- to 30-mo-old FBN rats) subjected to three cycles of
atrophy by hindlimb immobilization (plaster casts) with intervening recovery
periods. Our results indicated that there was a significant loss in gastrocnemius
muscle mass and in the proliferative potential of the resident satellite cells
after just one bout of immobilization. Neither the muscle mass nor the satellite
cell proliferation potential recovered from their atrophied values after either
the first 3-wk or later 9-wk recovery period. Remarkably, application of insulin
like growth factor I onto the atrophied gastrocnemius muscle for an additional 2
wk after this 9-wk recovery period rescued approximately 46% of the lost muscle
mass and dramatically increased proliferation potential of the satellite cells
from this muscle.
PMID- 11007572
TI - Lower limb skeletal muscle mass: development of dual-energy X-ray absorptiometry
prediction model.
AB - Although magnetic resonance imaging (MRI) can accurately measure lower limb
skeletal muscle (SM) mass, this method is complex and costly. A potential
practical alternative is to estimate lower limb SM with dual-energy X-ray
absorptiometry (DXA). The aim of the present study was to develop and validate
DXA-SM prediction equations. Identical landmarks (i.e., inferior border of the
ischial tuberosity) were selected for separating lower limb from trunk. Lower
limb SM was measured by MRI, and lower limb fat-free soft tissue was measured by
DXA. A total of 207 adults (104 men and 103 women) were evaluated [age 43 +/- 16
(SD) yr, body mass index (BMI) 24.6 +/- 3.7 kg/m(2)]. Strong correlations were
observed between lower limb SM and lower limb fat-free soft tissue (R(2) = 0.89,
P < 0.001); age and BMI were small but significant SM predictor variables. In the
cross-validation sample, the differences between MRI-measured and DXA-predicted
SM mass were small (-0.006 +/- 1.07 and -0.016 +/- 1.05 kg) for two different
proposed prediction equations, one with fat-free soft tissue and the other with
added age and BMI as predictor variables. DXA-measured lower limb fat-free soft
tissue, along with other easily acquired measures, can be used to reliably
predict lower limb skeletal muscle mass.
PMID- 11007573
TI - Effects of prior heavy exercise on phase II pulmonary oxygen uptake kinetics
during heavy exercise.
AB - We tested the hypothesis that heavy-exercise phase II oxygen uptake (VO(2))
kinetics could be speeded by prior heavy exercise. Ten subjects performed four
protocols involving 6-min exercise bouts on a cycle ergometer separated by 6 min
of recovery: 1) moderate followed by moderate exercise; 2) moderate followed by
heavy exercise; 3) heavy followed by moderate exercise; and 4) heavy followed by
heavy exercise. The VO(2) responses were modeled using two (moderate exercise) or
three (heavy exercise) independent exponential terms. Neither moderate- nor heavy
intensity exercise had an effect on the VO(2) kinetic response to subsequent
moderate exercise. Although heavy-intensity exercise significantly reduced the
mean response time in the second heavy exercise bout (from 65.2 +/- 4.1 to 47.0
+/- 3.1 s; P < 0.05), it had no significant effect on either the amplitude or the
time constant (from 23.9 +/- 1.9 to 25.3 +/- 2.9 s) of the VO(2) response in
phase II. Instead, this "speeding" was due to a significant reduction in the
amplitude of the VO(2) slow component. These results suggest phase II VO(2)
kinetics are not speeded by prior heavy exercise.
PMID- 11007574
TI - Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin
mediated mechanism.
AB - Neutrophil elastase has been linked to inflammatory lung diseases such as chronic
obstructive pulmonary disease, adult respiratory distress syndrome, emphysema,
and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil
elastase causes bronchoconstriction, but the mechanism by which this occurs is
not completely understood. Our laboratory previously showed that human neutrophil
elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK
has been identified as the major kininogenase of the airway and cleaves both high
and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled
bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic
patients and allergic sheep, we hypothesized that elastase-induced
bronchoconstriction could be mediated by bradykinin. To test this hypothesis, we
measured lung resistance (RL) in sheep before and after inhalation of porcine
pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B(2)
antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the
histamine H(1)-antagonist diphenhydramine hydrochloride, the cysteinyl
leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor
indomethacin. Inhaled PPE (125-1,000 microg) caused a dose-dependent increase in
RL. Aerosol challenge with a single 500 microg dose of PPE increased RL by 132 +/
8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI
200,355 (n = 6; P < 0.001), whereas treatment with diphenhydramine hydrochloride,
montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction.
Consistent with pharmacological data, TK activity in bronchial lavage fluid
increased 134 +/- 57% over baseline (n = 5; P < 0.02). We conclude that, in
sheep, PPE-induced bronchoconstriction is in part mediated by the generation of
bradykinin. Our findings suggest that elastase-kinin interactions may contribute
to changes in bronchial tone during inflammatory diseases of the airways.
PMID- 11007575
TI - Comparison of thermoregulatory responses between men and women immersed in cold
water.
AB - Eleven women (age = 24.4 +/- 6.3 yr, mass = 65.0 +/- 7.8 kg, height = 167 +/- 8
cm, body fatness = 22.4 +/- 5.9%, mean +/- SD) were immersed to neck level in 18
degrees C water for up to 90 min for comparison of their thermal responses with
those of men (n = 14) in a previous similarly conducted protocol. Metabolic rate
increased about three times resting levels in men and women, whereas the rate of
rectal temperature cooling (DeltaT(re)/Deltat) in women (0.47 degrees C/h) was
about one-half that in men. With use of all data, DeltaT(re)/Deltat correlates
with the ratio of body surface area to size and the metabolic rate of shivering
correlates inversely to the square root of body fatness. No significant gender
differences in total metabolic heat production normalized for body mass or
surface area were found among subjects who completed 90 min of immersion (9 women
and 7 men). Nor was there a gender difference in the overall percent contribution
( approximately 60%) of fat oxidation to total heat production. Blood
concentrations of free fatty acids, glycerol, beta-hydroxybutyrate, and lactate
increased significantly during the 90-min immersion, whereas muscle glycogen
sampled from the right quadriceps femoris vastus lateralis decreased (free fatty
acids, glycerol, and beta-hydroxybutyrate were higher in women). When the
subjects were subgrouped according to similar body fatness and 60 min of
immersion (6 women and 5 men), no significant gender differences emerged in
DeltaT(re)/Deltat, energy metabolism, and percent fat oxidation. These findings
suggest that no gender adjustments are necessary for prediction models of cold
response if body fatness and the ratio of body surface area to size are taken
into account and that a potential gender advantage with regard to carbohydrate
sparing during cold water immersion is not supported.
PMID- 11007576
TI - Insulin and exercise differentially regulate PI3-kinase and glycogen synthase in
human skeletal muscle.
AB - The purpose of this study was to determine the separate and combined effects of
exercise and insulin on the activation of phosphatidylinositol 3-kinase (PI3
kinase) and glycogen synthase in human skeletal muscle in vivo. Seven healthy men
performed three trials in random order. The trials included 1) ingestion of 2
g/kg body wt carbohydrate in a 10% solution (CHO); 2) 75 min of semirecumbent
cycling exercise at 75% of peak O(2) consumption; followed by 5 x 1-min maximal
sprints (Ex); and 3) Ex, immediately followed by ingestion of the carbohydrate
solution (ExCHO). Plasma glucose and insulin were increased (P < 0.05) at 15 and
30 (Post-15 and Post-30) min after the trial during CHO and ExCHO, although
insulin was lower for ExCHO. Hyperinsulinemia during recovery in CHO and ExCHO
led to an increase (P < 0.001) in PI3-kinase activity at Post-30 compared with
basal, although the increase was lower (P < 0. 004) for ExCHO. Furthermore, PI3
kinase activity was suppressed (P < 0.02) immediately after exercise (Post-0)
during Ex and ExCHO. Area under the insulin response curve for all trials was
positively associated with PI3-kinase activity (r = 0.66, P < 0.001). Glycogen
synthase activity did not increase during CHO but was increased (P < 0.05) at
Post-0 and Post-30 during Ex and ExCHO. Ingestion of the drink increased (P <
0.05) carbohydrate oxidation during CHO and ExCHO, although the increase after
ExCHO was lower (P < 0.05) than CHO. Carbohydrate oxidation was directly
correlated with PI3-kinase activity for all trials (r = 0.63, P < 0.001). In
conclusion, under resting conditions, ingestion of a carbohydrate solution led to
activation of the PI3-kinase pathway and oxidation of the carbohydrate. However,
when carbohydrate was ingested after intense exercise, the PI3-kinase response
was attenuated and glycogen synthase activity was augmented, thus facilitating
nonoxidative metabolism or storage of the carbohydrate. Activation of glycogen
synthase was independent of PI3-kinase.
PMID- 11007577
TI - Decrease in maximal voluntary contraction by tonic vibration applied to a single
synergist muscle in humans.
AB - The purpose of the study was to examine the effect of prolonged tonic vibration
applied to a single synergist muscle on maximal voluntary contraction (MVC) and
maximal rate of force development (dF/dt(max)). The knee extension MVC force and
surface electromyogram (EMG) from the rectus femoris (RF), vastus lateralis (VL),
and vastus medialis (VM) during MVC were recorded before and after vibration of
RF muscle at 30 Hz for 30 min. MVC, dF/dt(max), and the integrated EMG (iEMG) of
RF decreased significantly after prolonged tonic vibration in spite of no changes
in iEMG of VL and VM. The present results indicate that MVC and dF/dt(max) may be
influenced by the attenuated Ia afferent functions of a single synergist muscle.
PMID- 11007578
TI - Hypoxia inhibits amino acid uptake in human lung fibroblasts.
AB - Hypoxia and amino acid deprivation downregulate expression of extracellular
matrix genes in lung fibroblasts. We examined the effect of hypoxia on amino acid
uptake and protein formation in human lung fibroblasts. Low O(2) tension (0%
O(2)) suppressed incorporation of [(3)H]proline into type I collagen without
affecting [(35)S]methionine labeling of other proteins. Initial decreases in
intracellular [(3)H]proline incorporation occurred after 2 h of exposure to 0%
O(2), with maximal suppression of intracellular [(3)H]proline levels at 6 h of
treatment. Hypoxia significantly inhibited the uptake of radiolabeled proline, 2
aminoisobutyric acid (AIB), and 2-(methylamino)isobutyric acid (methyl-AIB) while
inducing minor decreases in leucine transport. Neither cycloheximide nor
indomethacin abrogated hypoxia-related suppression of methyl-AIB uptake. Efflux
studies demonstrated that hypoxia inhibited methyl-AIB transport in a
bidirectional fashion. The downregulation of amino acid transport was not due to
a toxic effect; function recovered on return to standard O(2) conditions. Kinetic
analysis of AIB transport revealed a 10-fold increase in K(m) accompanied by a
small increase in maximal transport velocity among cells exposed to 0% O(2).
These data indicate that low O(2) tension regulates the system A transporter by
decreasing transporter substrate affinity.
PMID- 11007579
TI - Ischemic exercise and the muscle metaboreflex.
AB - In exercising muscle, interstitial metabolites accumulate and stimulate muscle
afferents. This evokes the muscle metaboreflex and raises arterial blood pressure
(BP). In this report, we examined the effects of tension generation on muscle
metabolites and BP during ischemic forearm exercise in humans. Heart rate (HR),
BP, P(i), H(2)PO(4)(-), and pH ((31)P-NMR spectroscopy) data were collected in 10
normal healthy men (age 23 +/- 1 yr) during rhythmic handgrip exercise. After
baseline measurements, the subjects performed rhythmic handgrip for 2 min. At 2
min, a 250-mmHg occlusion cuff was inflated, and ischemic handgrip exercise was
continued until near fatigue (Borg 19). Measurements were continued for an
additional 30 s of ischemia. This protocol was performed at 15, 30, 45, and 60%
of the subjects' maximum voluntary contraction (MVC) in random order. As tension
increased, the time to fatigue decreased. In addition, mean arterial pressure and
HR were higher at 60% MVC than at any of the other lower tensions. The NMR data
showed significantly greater increases in H(2)PO(4)(-), P(i), and H(+) at 60%
than at 15 and 30% MVC. Therefore, despite the subjects working to the same
perceived effort level, a greater reflex response (represented by BP and HR data)
was elicited at 60% MVC than at any of the other ischemic tensions. These data
are consistent with the hypothesis that, as tension increases, factors aside from
insufficient blood flow contribute to the work effect on muscle metabolites and
the magnitude of the reflex response.
PMID- 11007580
TI - Diaspirin cross-linked hemoglobin improves oxygen extraction capabilities in
endotoxic shock.
AB - We studied the effects of diaspirin cross-linked hemoglobin (DCLHb), a cell-free
hemoglobin derived from human erythrocytes, on blood flow distribution and tissue
oxygen extraction capabilities in endotoxic shock. Eighteen pentobarbital sodium
anesthetized, mechanically ventilated dogs received 2 mg/kg of E. coli endotoxin,
followed by saline resuscitation to restore cardiac filling pressures to baseline
levels. The animals were randomly divided into three groups: six served as
control, six received DCLHb at a dose of 500 mg/kg (group 1) and six DCLHb at a
dose of 1,000 mg/kg (group 2). Cardiac tamponade was then induced by saline
injection in the pericardial sac to progressively reduce cardiac index and
thereby allow study of tissue oxygen extraction capabilities. DCLHb had a dose
dependent vasopressor effect but did not significantly alter cardiac index or
regional blood flow. During cardiac tamponade, critical oxygen delivery was 12.8
+/- 0.7 ml. kg(-1). min(-1) in the control group, but 8.6 +/- 0.9 and 8.2 +/- 0.7
ml. kg(-1). min(-1) in groups 1 and 2, respectively (both P < 0.05 vs. control
group). The critical oxygen extraction ratio was 39.1 +/- 3.1% in the control
group but 58.7 +/- 12.8% and 60.2 +/- 9.0% in groups 1 and 2, respectively. We
conclude that DCLHb can improve whole body oxygen extraction capabilities during
endotoxic shock in dogs.
PMID- 11007581
TI - Echocardiographic criteria for detection of postinfarction congestive heart
failure in rats.
AB - We evaluated postinfarction myocardial function in rats and determined
echocardiographic criteria for congestive heart failure (CHF) using high
performance echocardiography. Extensive myocardial infarction (MI) was induced in
rats by left coronary occlusion. Sham-operated animals served as controls. Five
weeks later, high-frame rate ( approximately 200 Hz), fully digitized, shallow
focus (10-25 mm), two-dimensional, M-mode and Doppler echocardiography was
performed. A J-tree cluster analysis was performed using parameters indicative of
CHF. Reproducibility was examined. The cluster analysis joined the animals into
one Sham and two MI clusters. One of the MI clusters had clinical characteristics
of CHF and elevated left ventricular end diastolic pressure. Among the
echocardiographic variables, only posterior wall shortening velocity separated
the failing and nonfailing MI clusters. We conclude that, by high frame rate
echocardiography, it is possible to obtain high- quality recordings in rats. It
is feasible to distinguish MI rats with CHF due to myocardial dysfunction from
those without failure and to perform longitudinal studies on myocardial function.
PMID- 11007583
TI - Collagen gene expression in rat left ventricle: interactive effect of age and
exercise training.
AB - Whether or not exercise training of sufficient intensity and duration to produce
left ventricle (LV) hypertrophy also regulates deposition of interstitial
collagen and cross-linking at the pretranslational level is unknown. Therefore,
the effects of exercise training on gene expression for the two principal
fibrillar collagens in LV, types I and III, were assessed in young adult (5 mo),
middle-aged (15 mo), and old (26 mo) rats. We also evaluated the potential
interaction of changes in mRNA for these procollagens with alterations in LV
extracellular matrix characteristics by simultaneously measuring collagen
concentration (hydroxyproline) and extent of mature collagen cross-linking
(hydroxylysylpyridinoline, HP). Ten weeks of treadmill running resulted in LV
hypertrophy and an increased maximal oxygen uptake in all three age groups of
trained rats compared with sedentary controls. Percent collagen in rat LV almost
doubled (P < 0.0001) from 5 to 26 mo of age, an increase unaffected by exercise
training. With aging, a significant decline in expression of mRNAs for both
collagen type I (P < 0.005) and type III (P < 0.001) was observed in LV free wall
(LVF) but not septum (LVS). Training prevented this decline in LVF mRNAs for the
two principal fibrillar collagens in middle-aged rats whereas it attenuated the
decline in senescent animals. HP concentration increased significantly with aging
in both LVF (P < 0.005) and LVS (P < 0.01). Training modulated this effect, but
again only in LVF, so that HP was significantly lower (P < 0.05) in this region
of the LV in old trained rats compared with sedentary counterparts. We conclude
that exercise training modulates the effects of aging on collagen gene mRNAs and
HP cross-linking regionally within the LV.
PMID- 11007582
TI - Effects of aortic nerve on hemodynamic response to obstructive apnea in sedated
pigs.
AB - In this study we test the hypothesis that aortic nerve traffic is responsible for
the pressor response to periodic apneas. In nine intubated, sedated chronically
instrumented pigs, periodic obstructive apneas were caused by occlusion of the
endotracheal tube for 30 s, followed by spontaneous breathing for 30 s. This was
done under control (C) conditions, after section of the aortic nerve (ANS), and
after bilateral cervical vagotomy (Vagot). Blood-gas tensions and airway pressure
changed similarly under all conditions: PO(2) decreased to 50-60 Torr, PCO(2)
increased to approximately 55 Torr, and airway pressure decreased by 40-50 mmHg
during apnea. With C, mean arterial pressure (MAP) increased from 111 +/- 4 mmHg
at baseline to 120 +/- 5 mmHg at late apnea (P < 0.01). After ANS and Vagot,
there was no change in MAP with apneas compared with baseline. Relative to
baseline, cardiac output and stroke volume decreased with C but not with ANS or
Vagot during apneas. Increased MAP was due to increased systemic vascular
resistance. Heart rate behaved similarly with C and ANS, being greater at early
interapnea than late apnea. With Vagot, heart rate increased throughout the apnea
interapnea cycle relative to baseline. We conclude that, in sedated pigs, aortic
nerve traffic mediates the increase in MAP and systemic vascular resistance
observed during periodic apneas. Increase in MAP is responsible for decreased
cardiac output and stroke volume. Additional vagal reflexes, most likely
parasympathetic efferents, are responsible for interacting with sympathetic
excitatory influences in modulating heart rate.
PMID- 11007584
TI - Synergist muscle ablation and recovery from nerve-repair grafting: contractile
and metabolic function.
AB - After nerve-repair grafting of medial gastrocnemius muscle, there is incomplete
recovery of specific force and sustainable power, perhaps due to overcompensation
by synergistic muscles. We hypothesized that increased workload due to synergist
ablation would enhance graft recovery. Contractile and metabolic properties of
control and nerve-repair grafted muscles, with and without synergist ablation,
were determined after 120 days recovery. Specific force (N/cm(2)) and normalized
power (W/kg) were less in the experimental groups compared with controls.
Sustained power (W/kg) in the synergist-ablated nerve-repair grafted muscle was
higher than nerve-repair grafted muscle, returning to control values. GLUT-4
protein was higher and glycogen content was diminished in both synergist-ablated
groups. In summary, synergist ablation did not enhance the recovery of specific
force or normalized power, but sustained power did recover, suggesting that
metabolic and not mechanical parameters were responsible for this recovery. The
enhanced endurance after synergist ablation was accompanied by increased GLUT-4
protein, suggesting a role for increased uptake of circulating glucose during
contraction.
PMID- 11007585
TI - Hyperbaric oxygen improves contractile function of regenerating rat skeletal
muscle after myotoxic injury.
AB - There is growing interest in hyperbaric oxygen (HBO) as an adjunctive treatment
for muscle injuries. This experiment tested the hypothesis that periodic
inhalation of HBO hastens the functional recovery and myofiber regeneration of
skeletal muscle after myotoxic injury. Injection of the rat extensor digitorum
longus (EDL) muscle with bupivacaine hydrochloride causes muscle degeneration.
After injection, rats breathed air with or without periodic HBO [100% O(2) at
either 2 or 3 atmospheres absolute (ATA)]. In vitro maximum isometric tetanic
force of injured EDL muscles and regenerating myofiber size were unchanged
between 2 ATA HBO-treated and untreated rats at 14 days postinjury but were
approximately 11 and approximately 19% greater, respectively, in HBO-treated rats
at 25 days postinjury. Maximum isometric tetanic force of injured muscles was
approximately 27% greater, and regenerating myofibers were approximately 41%
larger, in 3 ATA HBO-treated rats compared with untreated rats at 14 days
postinjury. These findings demonstrate that periodic HBO inhalation increases
maximum force-producing capacity and enhances myofiber growth in regenerating
skeletal muscle after myotoxic injury with greater effect at 3 than at 2 ATA.
PMID- 11007586
TI - Hindlimb unweighting alters endothelium-dependent vasodilation and ecNOS
expression in soleus arterioles.
AB - The purpose of this study was to test the hypothesis that endothelium-dependent
dilation is impaired in soleus resistance arteries from hindlimb-unweighted (HLU)
rats. Male Sprague-Dawley rats (300-350 g) were exposed to HLU (n = 14) or weight
bearing control (Con, n = 14) conditions for 14 days. After the 14-day treatment
period, soleus first-order (1A) arterioles were isolated and cannulated with
micropipettes to assess vasodilator responses to an endothelium-dependent
dilator, ACh (10(-9)-10(-4) M), and an endothelium-independent dilator, sodium
nitroprusside (SNP, 10(-9)-10(-4) M). Arterioles from HLU rats were smaller than
Con arterioles (maximal passive diameter = 140 +/- 4 and 121 +/- 4 microm in Con
and HLU, respectively) but developed similar spontaneous myogenic tone (43 +/- 3
and 45 +/- 3% in Con and HLU, respectively). Arteries from Con and HLU rats
dilated in response to increasing doses of ACh, but dilation was impaired in
arterioles from HLU rats (P = 0.03), as was maximal dilation to ACh (85 +/- 4 and
65 +/- 4% possible dilation in Con and HLU, respectively). Inhibition of nitric
oxide (NO) synthase (NOS) with N(omega)-nitro-L-arginine (300 microM) reduced ACh
dilation by approximately 40% in arterioles from Con rats and eliminated dilation
in arterioles from HLU rats. The cyclooxygenase inhibitor indomethacin (50
microM) did not significantly alter dilation to ACh in either group. Treatment
with N(omega)-nitro-L-arginine + indomethacin eliminated all ACh dilation in Con
and HLU rats. Dilation to sodium nitroprusside was not different between groups
(P = 0.98). To determine whether HLU decreased expression of endothelial cell NOS
(ecNOS), mRNA and protein levels were measured in single arterioles with RT-PCR
and immunoblot analysis. The ecNOS mRNA and protein expression was significantly
lower in arterioles from HLU rats than in Con arterioles (20 and 65%,
respectively). Collectively, these data indicate that HLU impairs ACh dilation in
soleus 1A arterioles, in part because of alterations in the NO pathway.
PMID- 11007587
TI - Effects of 2-G exposure on temperature regulation, circadian rhythms, and
adiposity in UCP2/3 transgenic mice.
AB - Altered ambient force environments affect energy expenditure via changes in
thermoregulation, metabolism, and body composition. Uncoupling proteins (UCPs)
have been implicated as potential enhancers of energy expenditure and may
participate in some of the adaptations to a hyperdynamic environment. To test
this hypothesis, this study examined the homeostatic and circadian profiles of
body temperature (T(b)) and activity and adiposity in wild-type and UCP2/3
transgenic mice exposed to 1 and 2 G. There were no significant differences
between the groups in the means, amplitudes, or phases of T(b) and activity
rhythms at either the 1- or 2-G level. Percent body fat was significantly lower
in transgenic (5.2 +/- 0. 2%) relative to the wild-type mice (6.2 +/- 0.1%) after
2-G exposure; mass-adjusted mesenteric and epididymal fat pads in transgenic mice
were also significantly lower (P < 0.05). The data suggest that 1) the actions of
two UCPs (UCP2 and UCP3) do not contribute to an altered energy balance at 2 G,
although 2) UCP2 and UCP3 do contribute to the utilization of lipids as a fuel
substrate at 2 G.
PMID- 11007588
TI - Exercise elevates plasma levels but not gene expression of IL-1beta, IL-6, and
TNF-alpha in blood mononuclear cells.
AB - Physical activity induces a subclinical inflammatory response, mediated in part
by leukocytes, and manifested by elevated concentrations of circulating
proinflammatory cytokines, including interleukin (IL)-1beta, IL-6, and tumor
necrosis factor-alpha (TNF-alpha). However, the source of the cytokines that
appear during exercise remains unknown. In this study, we examined exercise
induced changes in plasma cytokine concentrations and their corresponding mRNA
expression in peripheral blood mononuclear cells. Ten healthy [peak oxygen uptake
= 48.8 +/- 6.5 (SD) ml. kg(-1). min(-1)] but untrained men [age = 25 +/- 5 (SD)
yr] undertook 3 h of exercise (cycling and inclined walking) at 60-65% peak
oxygen uptake. Circulating leukocyte subset counts were elevated during and 2 h
postexercise but returned to normal within 24 h. Plasma concentrations of IL
1beta, IL-6, and TNF-alpha peaked at the end of exercise and remained elevated at
2 h (IL-6) and up to 24 h (IL-1beta and TNF-alpha) postexercise. Cytokine gene
expression in circulating mononuclear cells was measured by using the reverse
transcriptase-polymerase chain reaction; mRNA accumulation did not change with
exercise. In conclusion, mRNA accumulation of IL-1beta, IL-6, and TNF-alpha in
circulating mononuclear cells is not affected by 3 h of moderate endurance
exercise and does not seem to account for the observed increases in plasma
cytokines.
PMID- 11007589
TI - Vascular perturbations in the chronic orthostatic intolerance of the postural
orthostatic tachycardia syndrome.
AB - Chronic orthostatic intolerance is often related to the postural orthostatic
tachycardia syndrome (POTS). POTS is characterized by upright tachycardia.
Understanding of its pathophysiology remains incomplete, but edema and
acrocyanosis of the lower extremities occur frequently. To determine how arterial
and venous vascular properties account for these findings, we compared 13
patients aged 13-18 yr with 10 normal controls. Heart rate and blood pressure
were continuously recorded, and strain-gauge plethysmography was used to measure
forearm and calf blood flow, venous compliance, and microvascular filtration
while the subject was supine and to measure calf blood flow and calf size change
during head-up tilt. Resting venous pressure was higher in POTS compared with
control (16 vs. 10 mmHg), which gave the appearance of decreased compliance in
these patients. The threshold for edema formation decreased in POTS patients
compared with controls (8.3 vs. 16.3 mmHg). With tilt, early calf blood flow
increased in POTS patients (from 3.4 +/- 0.9 to 12.6 +/- 2.3 ml. 100 ml(-1). min(
1)) but did not increase in controls. Calf volume increased twice as much in POTS
patients compared with controls over a shorter time of orthostasis. The data
suggest that resting venous pressure is higher and the threshold for edema is
lower in POTS patients compared with controls. Such findings make the POTS
patients particularly vulnerable for edema fluid collection. This may signify a
redistribution of blood to the lower extremities even while supine, accounting
for tachycardia through vagal withdrawal.
PMID- 11007590
TI - Unilateral lung edema: effects on pulmonary gas exchange, hemodynamics, and
pulmonary perfusion distribution.
AB - Two types of unilateral lung edema in sheep were characterized regarding their
effects on pulmonary gas exchange, hemodynamics, and distribution of pulmonary
perfusion. One edema type was induced with aerosolized HCl (0.15 M, pH 1.0) and
the other with NaCl (0.15 M, pH 7.4). Both aerosols were nebulized continuously
for 4 h into left lungs. In HCl-treated animals, pulmonary gas exchange
deteriorated [from a partial arterial O(2) pressure-to-inspired O(2) fraction
ratio (Pa(O(2))/FI(O(2))) of 254 at baseline to 187 after 4 h HCl]. In addition,
pulmonary artery pressure and total pulmonary vascular resistance increased (from
16 to 19 mmHg and from 133 to 154 dyn. s. cm(-5), respectively). In NaCl-treated
animals, only the central venous pressure significantly increased (from 7 to 9
mmHg). Distribution of pulmonary perfusion (measured with fluorescent
microspheres) changed differently in both groups. After HCl application, 6% more
blood flow was directed to the treated lung, whereas, after NaCl, 5% more blood
flow was directed to the untreated lung. HCl and NaCl treatment both induce an
equivalent lung edema, but only HCl treatment is associated with gas exchange
alteration and tissue damage. Redistribution of pulmonary perfusion maintains gas
exchange during NaCl treatment and decreases it during HCl inhalation.
PMID- 11007591
TI - Scientific approach to the 1-h cycling world record: a case study.
AB - The purpose of this study was to describe the physiological and aerodynamic
characteristics and the preparation for a successful attempt to break the 1-h
cycling world record. An elite professional road cyclist (30 yr, 188 cm, 81 kg)
performed an incremental laboratory test to assess maximal power output (W(max))
and power output (W(OBLA)), estimated speed (V(OBLA)), and heart rate (HR(OBLA))
at the onset of blood lactate accumulation (OBLA). He also completed an
incremental velodrome (cycling track) test (VT1), during which V(OBLAVT1) and
HR(OBLAVT1) were measured and W(OBLAVT1) was estimated. W(max) was 572 W, W(OBLA)
505 W, V(OBLA) 52.88 km/h, and HR(OBLA) 183 beats/min. V(OBLAVT1), HR(OBLAVT1),
and W(OBLAVT1) were 52.7 km/h, 180 beats/min, and 500.6 W, respectively. Drag
coefficient and shape coefficient, measured in a wind tunnel, were 0. 244 and
0.65 m(2), respectively. The cyclist set a world record of 53,040 m, with an
estimated average power output of 509.5 W. Based on direct laboratory data of the
power vs. oxygen uptake relationship for this cyclist, this is slightly higher
than the 497. 25 W corresponding to his oxygen uptake at OBLA (5.65 l/min). In
conclusion, 1) the 1-h cycling world record is the result of the interaction
between physiological and aerodynamic characteristics; and 2) performance in this
event can be predicted using mathematical models that integrate the principal
performance-determining variables.
PMID- 11007592
TI - 5-Hydroxytryptophan-induced respiratory recovery after cervical spinal cord
hemisection in rats.
AB - The present study investigates the role of serotonin in respiratory recovery
after spinal cord injury. Experiments were conducted on C(2) spinal cord
hemisected, anesthetized, vagotomized, paralyzed, and artificially ventilated
rats in which end-tidal CO(2) was monitored and maintained. Before drug
administration, the phrenic nerve ipsilateral to hemisection showed no
respiratory-related activity due to the disruption of the descending bulbospinal
respiratory pathways by spinal cord hemisection. 5-Hydroxytryptophan (5-HTP), a
serotonin precursor, was administrated intravenously. 5-HTP induced time- and
dose-dependent increases in respiratory recovery in the phrenic nerve ipsilateral
to hemisection. Although the 5-HTP-induced recovery was initially accompanied by
an increase in activity in the contralateral phrenic nerve, suggesting an
increase in descending respiratory drive, the recovery persisted well after
activity in the contralateral nerve returned to predrug levels. 5-HTP-induced
effects were reversed by a serotonin receptor antagonist, methysergide. Because
experiments were conducted on animals subjected to C(2) spinal cord hemisection,
the recovery was most likely mediated by the activation of a latent respiratory
pathway spared by the spinal cord injury. The results suggest that serotonin is
an important neuromodulator in the unmasking of the latent respiratory pathway
after spinal cord injury. In addition, the results also suggest that the
maintenance of 5-HTP-induced respiratory recovery may not require a continuous
enhancement of central respiratory drive.
PMID- 11007593
TI - Alveolar epithelial integrity in athletes with exercise-induced hypoxemia.
AB - The effect of incremental exercise to exhaustion on the change in pulmonary
clearance rate (k) of aerosolized (99m)Tc-labeled diethylenetriaminepentaacetic
acid ((99m)Tc-DTPA) and the relationship between k and arterial PO(2) (Pa(O(2)))
during heavy work were investigated. Ten male cyclists (age = 25 +/- 2 yr, height
= 180.9 +/- 4.0 cm, mass = 80.1 +/- 9.5 kg, maximal O(2) uptake = 5. 25 +/- 0.35
l/min, mean +/- SD) completed a pulmonary clearance test shortly (39 +/- 8 min)
after a maximal O(2) uptake test. Resting pulmonary clearance was completed >/=24
h before or after the exercise test. Arterial blood was sampled at rest and at 1
min intervals during exercise. Minimum Pa(O(2)) values and maximum alveolar
arterial PO(2) difference ranged from 73 to 92 Torr and from 30 to 55 Torr,
respectively. No significant difference between resting k and postexercise k for
the total lung (0.55 +/- 0.20 vs. 0. 57 +/- 0.17 %/min, P > 0.05) was observed.
Pearson product-moment correlation indicated no significant linear relationship
between change in k for the total lung and minimum Pa(O(2)) (r = -0.26, P >
0.05). These results indicate that, averaged over subjects, pulmonary clearance
of (99m)Tc-DTPA after incremental maximal exercise to exhaustion in highly
trained male cyclists is unchanged, although the sampling time may have
eliminated a transient effect. Lack of a linear relationship between k and
minimum Pa(O(2)) during exercise suggests that exercise-induced hypoxemia occurs
despite maintenance of alveolar epithelial integrity.
PMID- 11007594
TI - pH(i) responses to osmotic cell shrinkage in the presence of open-system buffers.
AB - Changes in plasma volume in vivo cause rapid changes in extracellular pH by
altering the plasma bicarbonate concentration at a constant Pco(2) (Garella S,
Chang BS, and Kahn SI. Kidney Int 8: 279, 1975). Few studies have examined the
possibility that changes in cell volume produce comparable changes in
intracellular pH (pH(i)). In the present study, alveolar macrophages were exposed
to hyperosmotic medium in the absence or presence of the open-system buffers
CO(2)-HCO(3)(-), propionic acid-propionate, or NH(3)-NH(4)(+). In the absence of
open-system buffers, exposure to twice-normal osmolarity (2T) produced a slow
cellular alkalinization [change in pH(i) (DeltapH(i)) approximately 0.38;
exponential time constant (tau) approximately 120 s]. In the presence of 5%
CO(2), 2T caused a biphasic pH(i) response: a rapid increase (DeltapH(i)
approximately 0.10, tau approximately 15 s) followed by a slower pH(i) increase.
Identical rapid pH(i) increases were produced by 2T in the presence of propionic
acid (20 mM). Conversely, 2T caused a rapid pH(i) decrease (DeltapH(i)
approximately -0.21, tau approximately 10 s) in the presence of NH(3) (20 mM).
Thus osmotic cell shrinkage caused rapid pH(i) changes of opposite direction in
the presence of a weak acid buffer (contraction alkalosis with CO(2) or propionic
acid) vs. a weak base buffer (contraction acidosis with NH(3)). Graded DeltapH(i)
were produced by varying extracellular osmolarity in the presence of open-system
buffers; osmolarity increases of as little as 5-10% produced significant
DeltapH(i). The rapid pH(i) responses to 2T were insensitive to inhibitors of
membrane H(+) transport (ethylisopropylamiloride and bafilomycin A(1)). The
results are consistent with shrinkage-induced disequilibria in the total cellular
buffer system (i.e., intrinsic buffers plus added weak acid-base buffer).
PMID- 11007595
TI - A novel cell culture model for studying ischemia-reperfusion injury in lung
transplantation.
AB - Many cell culture models have been developed to study ischemia-reperfusion
injury; however, none is specific to the conditions of lung preservation and
transplantation. The objective of this study was to design a cell culture model
that mimics clinical lung transplantation, in which preservation is aerobic and
hypothermic. A549 cells, a human pulmonary epithelial cell line, were preserved
in 100% O(2) at 4 degrees C for varying periods in low-potassium dextran glucose
solution, simulating ischemia, followed by the introduction of warm (37 degrees
C) DMEM plus 10% fetal bovine serum to simulate reperfusion. Cultures were
assayed for cell attachment and viability. Sequential extension of ischemic times
to 24 h showed a time-dependent loss of cells. There was a further decrease in
cell number after simulated reperfusion. Cell detachment was due mainly to cell
death, as determined by cell viability. The effects of chemical components such
as dextran 40 and calcium in the preservation solution and various preservation
gas mixtures were examined by use of this model system. With its design and
validation, this model could be used to study mechanisms related to ischemia
reperfusion injury at the cellular and molecular level.
PMID- 11007596
TI - Systemic hypoxia increases leukocyte emigration and vascular permeability in
conscious rats.
AB - We recently observed that acute systemic hypoxia produces rapid increases in
leukocyte adherence in the mesenteric microcirculation of the anesthetized rat
Wood JG, Johnson JS, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 1734-1740,
1999; Wood JG, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 873-881, 1999.
Hypoxia-induced leukocyte adherence is associated with an increase in reactive
oxygen species (ROS) generation and is attenuated by antioxidants or
interventions that increase tissue levels of nitric oxide (NO). These results
suggest that the acute effects of hypoxia on leukocyte-endothelial interactions
are caused by a change in the ROS-NO balance. The present experiments were
designed to extend our observations of the initial microcirculatory response to
hypoxia; specifically, we wanted to determine whether the response to systemic
hypoxia involves increased microvascular permeability and leukocyte emigration
and whether ROS generation and decreased NO levels contribute to these responses.
At this time, there is conflicting evidence, from in vitro studies, regarding the
effect of hypoxia on these indexes of vascular function. Our studies were carried
out in the physiological setting of the conscious animal, in which a prolonged
hypoxic exposure is possible without the adverse effects that may develop under
anesthesia. The central observation of these studies is that conscious animals
exposed for 4 h to environmental hypoxia show increased microvascular
permeability and emigration of leukocytes into the extravascular space of the
mesenteric circulation. Furthermore, these events are dependent on increased ROS
generation and, possibly, a subsequent decrease in tissue NO levels during
systemic hypoxia. Our results show that systemic hypoxia profoundly affects
vascular endothelial function through changes in the ROS-NO balance in the
conscious animal.
PMID- 11007597
TI - Electrical admittance for filling of the heart during lower body negative
pressure in humans.
AB - To evaluate whether electrical admittance of intracellular water is applicable
for monitoring filling of the heart, we determined the difference in
intracellular water in the thorax (Thorax(ICW)), measured as the reciprocal value
of the electrical impedance for the thorax at 1.5 and 100 kHz during lower body
negative pressure (LBNP) in humans. Changes in Thorax(ICW) were compared with
positron emission tomography-determined C(15)O-labeled erythrocytes over the
heart. During -40 mmHg LBNP, the blood volume of the heart decreased by 21 +/- 3%
as the erythrocyte volume was reduced by 20 +/- 2% and the plasma volume declined
by 26 +/- 2% (P < 0.01; n = 8). Over the heart region, LBNP was also associated
with a decrease in the technetium-labeled erythrocyte activity by 26 +/- 4% and,
conversely, an increase over the lower leg by 92 +/- 5% (P < 0.01; n = 6). For 15
subjects, LBNP increased thoracic impedance by 3.3 +/- 0.3 Omega (1.5 kHz) and
3.0 +/- 0.4 Omega (100 kHz), whereas leg impedance decreased by 9.0 +/- 3.3 Omega
(1.5 kHz) and 6.1 +/- 3 Omega (100 kHz; P < 0.01). Thorax(ICW) was reduced by 7.1
+/- 1.9 S. 10(-4) (P < 0.01) and intracellular water in the leg tended to
increase (from 37.8 +/- 4.6 to 40.9 +/- 5.0 S. 10(-4); P = 0.08). The correlation
between Thorax(ICW) and heart erythrocyte volume was 0.84 (P < 0.05). The results
suggest that thoracic electrical admittance of intracellular water can be applied
to evaluate changes in blood volume of the heart during LBNP in humans.
PMID- 11007598
TI - Description and validation of a novel liquid metal-free device for venous
congestion plethysmography.
AB - We present a newly developed electromechanical sensor with automated calibration
for strain-gauge plethysmography (filtrass) and compare it to a conventional
mercury-in-Silastic strain-gauge plethysmograph (MSG). Fluid filtration capacity
(K(f)) and isovolumetric venous pressure (Piv) of the limb were assessed
noninvasively with both devices in 29 healthy volunteers. We found significantly
higher K(f) and Piv values with MSG [4.6 +/- 2.0 x 10(-3) ml. min(-1). mmHg(-1).
100 ml tissue(-1) (K(f) units; K(f)U) and 21.2 +/- 8.1 mmHg for Pvi], than with
filtrass, giving values of 3.1 +/- 0.8 K(f)U and 15.1 +/- 7.1 mmHg. Because K(f)
and Piv are profoundly influenced by the calibration, we investigated the quality
of the calibration signal and its impact on the obtained values. We could show
that the reproducibility of repeated calibrations was higher with filtrass (58%
lower mean +/- SD). The data were grouped according to the quality of
calibration, and we found no significant difference in K(f) and Piv between
filtrass (3.0 +/- 0.7 K(f)U and 15.9 +/- 6.9 mmHg, respectively) and MSG with
good calibration signal (3.3 +/- 0. 8 K(f)U and 18.6 +/- 7.1 mmHg, respectively;
no significant difference). However, we obtained significantly higher MSG values
(5. 6 +/- 2.0 K(f)U and 23.1 +/- 8.4 mmHg, respectively; P < 0.001) in the group
with a bad calibration signal. We suggest that the filtrass sensor, which
performs an automatic, standardized calibration procedure and shows a linear
signal response to stretch, gives highly reproducible and reliable results and
thus is more suitable for routine application.
PMID- 11007599
TI - Effect of transpulmonary pressure on airway diameter and responsiveness of
immature and mature rabbits.
AB - We previously demonstrated that airway responsiveness is greater in immature than
in mature rabbits; however, it is not known whether there are maturational
differences in the effect of transpulmonary pressure (Ptp) on airway size and
airway responsiveness. The relationship between Ptp and airway diameter was
assessed in excised lungs insufflated with tantalum powder. Diameters of
comparable intraparenchymal airway segments were measured from radiographs
obtained at Ptp between 0 and 20 cmH(2)O. At Ptp > 8 cmH(2)O, the diameters were
near maximal in both groups. With diameter normalized to its maximal value,
changing Ptp between 8 and 0 cmH(2)O resulted in a greater decline of airway
caliber in immature than mature airways. The increases in lung resistance (RL) in
vivo at Ptp of 8, 5, and 2 cmH(2)O were measured during challenge with
intravenous methacholine (MCh: 0.001-0.5 mg/kg). At Ptp of 8 cmH(2)O, both groups
had very small responses to MCh and the maximal fold increases in RL did not
differ (1.93 +/- 0.29 vs. 2.23 +/- 0.19). At Ptp of 5 and 2 cmH(2)O, the fold
increases in RL were greater for immature than mature animals (13.19 +/- 1.81 vs.
3.89 +/- 0.37) and (17.74 +/- 2.15 vs. 4.6 +/- 0.52), respectively. We conclude
that immature rabbits have greater airway distensibility and this difference may
contribute to greater airway narrowing in immature compared with mature rabbits.
PMID- 11007600
TI - Influence of lung volume on pulmonary microvascular pressure-volume
characteristics.
AB - The pressure-volume (P-V) characteristics of the lung microcirculation are
important determinants of the pattern of pulmonary perfusion and of red and white
cell transit times. Using diffuse light scattering, we measured capillary P-V
loops in seven excised perfused dog lobes at four lung volumes, from functional
residual capacity (FRC) to total lung capacity (TLC), over a wide range of
vascular transmural pressures (Ptm). At Ptm 5 cmH(2)O, specific compliance of the
microvasculature was 8.6%/cmH(2)O near FRC, decreasing to 2.7%/cmH(2)O as lung
volume increased to TLC. At low lung volumes, the vasculature showed signs of
strain stiffening (specific compliance fell as Ptm rose), but stiffening
decreased as lung volume increased and was essentially absent at TLC. The P-V
loops were smooth without sharp transitions, consistent with vascular distension
as the primary mode of changes in vascular volume with changes in Ptm. Hysteresis
was small (0.013) at all lung volumes, suggesting that, although surface tension
may set basal capillary shape, it does not strongly affect capillary compliance.
PMID- 11007601
TI - Influence of microgravity on crystal formation in biomineralization.
AB - Biomineralized tissues are widespread in animals. They are essential elements in
skeletons and in statocysts. The function of both can only be understood with
respect to gravitational force, which has always been present. Therefore, it is
not astonishing to identify microgravity as a factor influencing
biomineralization, normally resulting in the reduction of biomineralized
materials. All known biominerals are composite materials, in which the organic
matrix and the inorganic materials, organized in crystals, interact. If, during
remodeling and turnover processes under microgravity, a defective organization of
these crystals occurs, a reduction in biomineralized materials could be the
result. To understand the influence of microgravity on the formation of
biocrystals, we studied the shell-building process of the snail Biomphalaria
glabrata as a model system. We show that, under microgravity (space shuttle
flights STS-89 and STS-90), shell material is built in a regular way in both
adult snails and snail embryos during the beginning of shell development.
Microgravity does not influence crystal formation. Because gravity has constantly
influenced evolution, the organization of biominerals with densities near 3 must
have gained independence from gravitational forces, possibly early in evolution.
PMID- 11007602
TI - Effects of voluntary activity and genetic selection on muscle metabolic
capacities in house mice Mus domesticus.
AB - Selective breeding is an important tool in behavioral genetics and evolutionary
physiology, but it has rarely been applied to the study of exercise physiology.
We are using artificial selection for increased wheel-running behavior to study
the correlated evolution of locomotor activity and physiological determinants of
exercise capacity in house mice. We studied enzyme activities and their response
to voluntary wheel running in mixed hindlimb muscles of mice from generation 14,
at which time individuals from selected lines ran more than twice as many
revolutions per day as those from control (unselected) lines. Beginning at
weaning and for 8 wk, we housed mice from each of four replicate selected lines
and four replicate control lines with access to wheels that were free to rotate
(wheel-access group) or locked (sedentary group). Among sedentary animals, mice
from selected lines did not exhibit a general increase in aerobic capacities: no
mitochondrial [except pyruvate dehydrogenase (PDH)] or glycolytic enzyme activity
was significantly (P < 0.05) higher than in control mice. Sedentary mice from the
selected lines exhibited a trend for higher muscle aerobic capacities, as
indicated by higher levels of mitochondrial (cytochrome-c oxidase, carnitine
palmitoyltransferase, citrate synthase, and PDH) and glycolytic (hexokinase and
phosphofructokinase) enzymes, with concomitant lower anaerobic capacities, as
indicated by lactate dehydrogenase (especially in male mice). Consistent with
previous studies of endurance training in rats via voluntary wheel running or
forced treadmill exercise, cytochrome-c oxidase, citrate synthase, and carnitine
palmitoyltransferase activity increased in the wheel-access groups for both
genders; hexokinase also increased in both genders. Some enzymes showed gender
specific responses: PDH and lactate dehydrogenase increased in wheel-access male
but not female mice, and glycogen phosphorylase decreased in female but not in
male mice. Two-way analysis of covariance revealed significant interactions
between line type and activity group; for several enzymes, activities showed
greater changes in mice from selected lines, presumably because such mice ran
more revolutions per day and at greater velocities. Thus genetic selection for
increased voluntary wheel running did not reduce the capability of muscle aerobic
capacity to respond to training.
PMID- 11007603
TI - Biology lessons from oscillatory cell mechanics.
PMID- 11007604
TI - Mechanical properties of cultured human airway smooth muscle cells from 0.05 to
0.4 Hz.
AB - We investigated the rheological properties of living human airway smooth muscle
cells in culture and monitored the changes in rheological properties induced by
exogenous stimuli. We oscillated small magnetic microbeads bound specifically to
integrin receptors and computed the storage modulus (G') and loss modulus (G")
from the applied torque and the resulting rotational motion of the beads as
determined from their remanent magnetic field. Under baseline conditions, G'
increased weakly with frequency, whereas G" was independent of the frequency. The
cell was predominantly elastic, with the ratio of G" to G' (defined as eta) being
approximately 0. 35 at all frequencies. G' and G" increased together after
contractile activation and decreased together after deactivation, whereas eta
remained unaltered in each case. Thus elastic and dissipative stresses were
coupled during changes in contractile activation. G' and G" decreased with
disruption of the actin fibers by cytochalasin D, but eta increased. These
results imply that the mechanisms for frictional energy loss and elastic energy
storage in the living cell are coupled and reside within the cytoskeleton.
PMID- 11007605
TI - Brief commentary on coronary wave-intensity analysis.
PMID- 11007606
TI - Wave-intensity analysis: a new approach to coronary hemodynamics.
AB - In 10 anesthetized dogs, we measured high-fidelity left circumflex coronary
(P(LCx)), aortic (P(Ao)), and left ventricular (P(LV)) pressures and left
circumflex velocity (U(LCx); Doppler) and used wave-intensity analysis (WIA) to
identify the determinants of P(LCx) and U(LCx). Dogs were paced from the right
atrium (control 1) or right ventricle by use of single (control 2) and then
paired pacing to evaluate the effects of left ventricular contraction on P(LCx)
and U(LCx). During left ventricular isovolumic contraction, P(LCx) exceeded
P(Ao), paired pacing increasing the difference. Paired pacing increased DeltaP(X)
(the P(LCx)-P(Ao) difference at the P(Ao)-P(LV) crossover) and average dP(LCx)/dt
(P < 0.0001 for both). During this time, WIA identified a backward-going
compression wave (BCW) that increased P(LCx) and decreased U(LCx); the BCW
increased during paired pacing (P < 0.0001). After the aortic valve opened, the
increase in P(Ao) caused a forward-going compression wave that, when it exceeded
the BCW, caused U(LCx) to increase, despite P(LV) and (presumably) elastance
continuing to increase. Thus WIA identifies the contributions of upstream
(aortic) and downstream (microcirculatory) effects on P(LCx) and U(LCx).
PMID- 11007608
TI - commentary
PMID- 11007607
TI - Invited review: mechanisms of ventilator-induced lung injury: a perspective.
AB - Despite advances in critical care, the mortality rate in patients with acute lung
injury remains high. Furthermore, most patients who die do so from multisystem
organ failure. It has been postulated that ventilator-induced lung injury plays a
key role in determining the negative clinical outcome of patients exposed to
mechanical ventilation. How mechanical ventilation exerts its detrimental effect
is as of yet unknown, but it appears that overdistension of lung units or shear
forces generated during repetitive opening and closing of atelectatic lung units
exacerbates, or even initiates, significant lung injury and inflammation. The
term "biotrauma" has recently been elaborated to describe the process by which
stress produced by mechanical ventilation leads to the upregulation of an
inflammatory response. For mechanical ventilation to exert its deleterious
effect, cells are required to sense mechanical forces and activate intracellular
signaling pathways able to communicate the information to its interior. This
information must then be integrated in the nucleus, and an appropriate response
must be generated to implement and/or modulate its response and that of
neighboring cells. In this review, we present a perspective on ventilator-induced
lung injury with a focus on mechanisms and clinical implications. We highlight
some of the most recent findings, which we believe contribute to the generation
and propagation of ventilator-induced lung injury, placing a special emphasis on
their implication for future research and clinical therapies.
PMID- 11007609
TI - Invited review: effects of flow on vascular endothelial intracellular calcium
signaling of rat aortas ex vivo.
AB - To study the effects of flow on in situ endothelial intracellular calcium
concentration ([Ca(2+)](i)) signaling, rat aortic rings were loaded with fura 2,
mounted on a tissue flow chamber, and divided into control and flow-pretreated
groups. The latter was perfused with buffer at a shear stress of 50 dyns/cm(2)
for 1 h. Endothelial [Ca(2+)](i) responses to ACh or shear stresses were
determined by ratio image analysis. Moreover, ACh-induced [Ca(2+)](i) elevation
responses were measured in a calcium-free buffer, or in the presence of SKF
96365, to elucidate the role of calcium influx in the flow effects. Our results
showed that 1) ACh increased endothelial [Ca(2+)](i) in a dose-dependent manner,
and these responses were incremented by flow-pretreatment; 2) the differences in
ACh-induced [Ca(2+)](i) elevation between control and flow-pretreated groups were
abolished by SKF-96365 or by Ca(2+)-free buffer; and 3) in the presence of 10(-5)
M ATP, shear stress induced dose-dependent [Ca(2+)](i) elevation responses that
were not altered by flow-pretreatment. In conclusion, flow-pretreatment augments
the ACh-induced endothelial calcium influx in rat aortas ex vivo.
PMID- 11007610
TI - Opposing views on tensegrity as a structural framework for understanding cell
mechanics.
PMID- 11007611
TI - The foreign body reaction to a biodegradable biomaterial differs between rats and
mice.
AB - Before a biomaterial can be applied in the clinic, biocompatibility must be
tested in in vivo models, by monitoring the foreign body reaction. In this study,
we compared the foreign body reaction (FBR) to the biodegradable biomaterial
hexamethylenediisocyanate crosslinked dermal sheep collagen (HDSC) between
several strains of rats and mice. HDSC disks were implanted subcutaneously on the
backs of AO, BN, F344, LEW, and PVG rats and on the backs of 129 SVEV, BALB/c,
and C57BL/6 mice. Materials were explanted after 7, 14, 21, and 28 days and
processed for (immuno) light and transmission electron microscopic evaluation. In
all rat strains, giant cell formation and phagocytosis of HDSC bundles were
comparable. In addition, in the PVG rat, many plasma cells infiltrated the HDSC
disks. Only a few T cells were present in AO and PVG rats, whereas, in F344 and
LEW rats, the presence of T cells was more pronounced. BN rats showed an
intermediate T-cell infiltration. In mice, the FBR to HDSC was comparable between
the different strains. Compared with rats, giant cell formation was limited,
whereas stroma formation was more abundant. Phagocytosis of HDSC bundles rarely
occurred in mice, whereas calcification was observed more often. It is concluded
that the FBR to HDSC clearly differs between rats and mice. This has consequences
for assessment studies on biocompatibility and also on fundamental biomaterial
research.
PMID- 11007612
TI - Surface morphology and wear mechanisms of four clinically relevant biomaterials
after hip simulator testing.
AB - The surfaces of worn components hold clues to the underlying wear mechanisms.
Previous evidence suggested that the absolute wear rates of acetabular components
in a hip simulator were related to mechanical behavior; we hypothesized that the
surface morphology of the liners might also be sensitive to mechanical
properties. A noncontact, three-dimensional surface topography measurement system
based on white light interferometry was used to quantify the surface morphology
of ultra-high molecular weight polyethylene, polytetrafluoroethylene, high
density polyethylene, and polyacetal liners, and their corresponding femoral
heads, after 3 million cycles in a multi-directional hip simulator. Comparisons
were made with the fatigue soaked and control (as machined) components.
Statistically significant power law relationships were observed between the
arithmetic mean surface roughness (R(a)) of the worn acetabular liners and the
volumetric wear rate in the hip simulator (p < 0.01, r(2) = 0.52). Significant
relationships were also observed between R(a) and the elastic and large
deformation mechanical behavior of the liner materials, measured directly from
the wear-tested liners using the small punch test (p < 0.01, r(2) = 0.54-0.81).
The results support the hypothesis that wear mechanisms of acetabular liners
during hip simulator testing are related to surface morphology in conjunction
with the mechanical behavior of the polymeric materials.
PMID- 11007613
TI - The expression of bone matrix protein mRNAs around beta-TCP particles implanted
into bone.
AB - Tissue response around beta-tricalcium phosphate (beta-TCP) particles (150-300
microm in diameter) implanted into rat tibiae was analyzed by in situ
hybridization with digoxigenin-labeled procollagen alpha1(I) (COL), osteonectin,
osteocalcin, and osteopontin (OPN) RNA probes. Specimens were collected at 3, 5,
7, and 10 days after the operation. Holes without implantation were used as
control. In both the beta-TCP implanted and control groups, new bone was formed
centripetally and all four kinds of mRNA were expressed in activated osteoblasts.
A COL signal was expressed most strongly and widely, and was detected at the
peripheral region of the hole at day 3. The other three mRNAs were also expressed
in bone forming osteoblasts by day 7. However, in the earlier cell reaction
stage, OPN expression in the beta-TCP implanted group was different than that in
the control group: OPN mRNA was seen exclusively in the cells on the particles,
and an OPN signal was detected not only in COL-positive cells, but also in COL
negative cells. The former cells may be osteoblasts and reflect the early process
of bone formation on biomaterials. The latter cells may be macrophages and
reflect foreign body reactions. Expression of these OPN mRNAs induced by
implantation of beta-TCP may play a role in bone formation on the materials and
in determining their biocompatibility.
PMID- 11007614
TI - Biocompatibility of electroactive polymers in tissues.
AB - The biocompatibility of ethylene-vinyl acetate copolymer (EVAc), polyethylene
(PE), and polyaniline (PANi) films in the emeraldine (EM), nigraniline (NA) and
leucoemeraldine (LM) intrinsic oxidation states were assessed through
subcutaneous implantation into male Sprague-Dawley rats beneath the dorsal skin,
for a period ranging from 19 to 90 weeks. Histological examination, interstitial
pressure measurement, and X-ray photoelectron spectroscopy (XPS) were employed to
determine the biocompatibility of the polymers. The polymers did not provoke
inflammatory responses in the subcutaneous tissues over the entire implantation
period. Characteristics features associated with tissue-implant incompatibility
were not evident near the implantation. Interstitial pressure was measured to
evaluate the development of tissue. Low interstitial pressure readings on the
region of implantation confirmed the biocompatibility of these polymer types. The
surface composition of the electroactive aniline polymers before and after the
implantation was characterized by XPS.
PMID- 11007615
TI - Biocompatibility evaluation of dental metal alloys in vitro: expression of
extracellular matrix molecules and its relationship to cell proliferation rates.
AB - The biocompatibility in vitro of dental biomaterials has been widely studied,
with consideration of cell viability and cell proliferation rates. In the present
study we evaluated the biocompatibility in vitro of three single-phase dental
metal alloys, all provided by the same manufacturer. To this aim, we considered
the percentage of proliferating cells revealed by 5-bromodeoxyuridine
incorporation in human fibroblast cultures in the presence of these biomaterials,
performing a short time test (72 h). These data were correlated with
immunocytochemical expression of four molecules of the extracellular matrix,
i.e., fibronectin, type I collagen, beta(1)-integrin subunit, and chondroitin
sulfate, because the capability of cells to adhere to substrata is widely related
to cell proliferation rates. Alloys presenting higher amounts of noble elements
were more biocompatible even when they contained significant amount of both Ag
and Cu. As regards the expression of the extracellular matrix molecules, the
organization level of fibronectin in fibrils was correlated with higher cell
proliferation rates, whereas no difference was detected for the expression of the
other antigens. On these bases, we assume that expression of fibronectin could be
a useful parameter in evaluation of biocompatibility in addition to cell
proliferation capability.
PMID- 11007616
TI - Cyclic fatigue-crack propagation in sapphire in air and simulated physiological
environments.
AB - Single-crystal aluminas are being considered for use in the manufacture of
prosthetic heart valves. To characterize such materials for biomedical
application, subcritical crack growth by stress corrosion (static fatigue) and by
cyclic fatigue has been examined in sapphire along (1100) planes in 24 degrees C
humid air and 37 degrees C Ringer's solution (the latter as a simulated
physiological environment). The relationships between crack-propagation rates and
the linear-elastic stress intensity have been determined for the first time in
sapphire for both modes of subcritical cracking. It was found that growth rates
were significantly faster at a given stress intensity in the Ringer's solution
compared to the humid air environment. Mechanistically, a true cyclic fatigue
effect was not found in sapphire as experimentally measured cyclic fatigue-crack
growth rates could be closely predicted simply by integrating the static fatigue
crack growth data over the cyclic loading cycle.
PMID- 11007617
TI - Novel beta-emitting poly(ethylene terephthalate) surface modification.
AB - Restenosis after percutaneous interventions in coronary and peripheral arteries
leads to repeat procedures and surgery in a significant number of patients. We
have previously demonstrated that irradiation of an arterial site using an
endovascular source (brachytherapy) is highly effective in preventing the
restenotic process. To this end, a novel beta radiation delivery system was
developed, based on the adsorption of (32)P (o-phosphoric acid) by pH-sensitive
chitosan hydrogel on a poly(ethylene terephthalate) (PET) balloon surface. The
PET balloon surface was treated with oxygen plasma and coated with chitosan
hydrogel. Covalent bonds, ionic bonds, and hydrogen bonds all contribute to the
adhesion between chitosan hydrogel and PET. In the aqueous phosphoric acid (PA)
solution, the -NH(2) groups of chitosan were protonated by PA and the adsorption
of PA occurred at the same time. The effect of PA concentration and temperature
on adsorption efficiency and kinetics were studied. More than 70% PA was adsorbed
on the sample surface in 0.2 mM PA solution. The surface of samples was also
investigated by attenuated total reflection-Fourier transform infrared
spectroscopy and scanning electron microscopy. PET surface may be modified to
carry high activity beta emitters; such materials may be useful in a therapeutic
setting
PMID- 11007618
TI - Evaluation of calcium phosphates and experimental calcium phosphate bone cements
using osteogenic cultures.
AB - In this study, rat bone marrow cells (RBM) were used to evaluate two
biodegradable calcium phosphate bone cements and bioactive calcium phosphate
ceramics. The substances investigated were: two novel calcium phosphate cements,
Biocement F and Biocement H, tricalcium phosphate (TCP), surface-modified alpha
tricalcium phosphate [TCP (s)] and a rapid resorbable calcium phosphate ceramic
consisting of CaKPO(4) (sample code R5). RBM cells were cultured on disc-shaped
test substrates for 14 days. The culture medium was changed daily and also
examined for calcium, phosphate, and potassium concentrations. Specimens were
evaluated using light microscopy, and morphometry of the cell-covered substrate
surface, scanning electron microscopy, and energy dispersive X-ray analysis and
morphometry of the cell-covered substrate surface. Areas of mineralization were
identified by tetracyline labeling. Except for R 5, rat bone-marrow cells
attached and grew on all substrate surfaces. Of the different calcium phosphate
materials tested, TCP and TCP (s) facilitated osteoblast growth and extracellular
matrix elaboration to the highest degree, followed by Biocements H and F. The
inhibition of cell growth encountered with R 5 seems to be related to its high
phosphate and potassium ion release.
PMID- 11007619
TI - Effect of anti-inflammatory medication on monocyte response to titanium
particles.
AB - Cytokines produced by macrophages in the periprosthetic membranes surrounding
joint replacements have been implicated as causal agents in osteolysis and
prosthetic loosening. The present study characterizes the response of human
peripheral blood monocytes to titanium particles. Monocytes were obtained from
donated blood and were cultured in the presence of different-sized titanium
particles. Exposure to titanium-aluminum-vanadium particles significantly changed
the release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and
interleukin-1 (IL-1), whereas there was no significant effect on the release of
prostaglandin E(2) (PGE(2)). When monocytes were cultured with particles, the
titanium alloy particles induced significantly more release of TNF-alpha and less
IL-1 secretion. Ciprofloxacin inhibited production of TNF-alpha, IL-6, IL-1, and
PGE(2) in human monocytes exposed to titanium particles. In contrast to
ciprofloxacin, indomethacin was not a potent inhibitor of TNF-alpha production
but potentiated IL-6 production in titanium-stimulated monocytes. Indomethacin
had no effect on the production of IL-1 and was a potent inhibitor of PGE(2)
production in titanium-stimulated monocytes. Pentoxifylline had an inhibitor
effect on TNF-alpha production in titanium-stimulated monocytes. Pentoxifylline
potentiated IL-6 and IL-1 production in monocytes exposed to titanium particles
and had a biphasic effect on the PGE(2) production. The results of this study
support our hypothesis that human monocytes release bone resorption mediators
after in vitro exposure to TiAlV alloy particles. The results also demonstrate
the differences of bone-resorbing mediators in response to different wear
particle size. The pharmacologic agents (ciprofloxacin, pentoxifylline, and
indomethacin) that can modulate the release of bone resorbing mediators such as
PGE(2), TNF-alpha, IL-1, and IL-6 release from human monocytes. The results help
to elucidate the differences in cellular response to wear particles but may not
be directly transposed to the human situation.
PMID- 11007620
TI - Acute cellular interaction with textured surfaces in blood contact.
AB - Textured blood-contacting surfaces can promote the formation of a blood
compatible pseudo-neointima. We hypothesized that by controlling the surface
texturing, the pseudo-neointima thickness could be controlled. The hypothesis was
tested experimentally by fabricating the polyurethane textured surfaces with
three different fiber lengths, and exposing them simultaneously to the flowing
blood in an ovine ex vivo carotid-jugular series shunt for periods up to 4 h. The
textured surface consisted of regularly spaced tapered micro-fibers of defined
length on a smooth base-plane surface. Because of the simple surface topography,
detailed computational fluid-dynamic modeling of the surface could be obtained as
a parallel study. Experimental results showed that white cell was the predominant
cell type deposited on the textured surfaces, whereas macroscopic thrombus
formation occurred only in one of nine blood-contacting experiments. White cell
density on the textured base-plane surface was subsequently quantified by image
analyzing the electron micrographs of blood-contacted textured surfaces. The
statistical analysis of cell densities on individual textured surfaces showed
effects of wall shear stress on the textured base plane (which was obtained from
the fluid-dynamic modeling), the longitudinal position of the test section in the
series shunt, and blood-contact time.
PMID- 11007621
TI - Tissue reactions after subcutaneous and intraosseous implantation of mineral
trioxide aggregate and ethoxybenzoic acid cement.
AB - Biocompatibility of mineral trioxide aggregate and ethoxybenzoic acid cement was
investigated by subcutaneous and intraosseous implantation of the materials in
rats. Tissue reactions were studied at 15, 30, and 60 days after implantation.
Subcutaneous implantation of mineral trioxide aggregate initially elicited severe
reactions with coagulation necrosis and dystrophic calcification; the reactions,
however, subsided to mostly moderate with time. Subcutaneous implantation of
ethoxybenzoic acid cement initially elicited mostly moderate reactions that
subsided to mild in time. Osteogenesis was not observed with either material upon
subcutaneous implantation indicating that neither material is osteoinductive.
Reactions to intraosseous implants of both materials were less intense than with
subcutaneous implantation. Osteogenesis occurred in association with intraosseous
implants indicating that both materials are osteoconductive.
PMID- 11007622
TI - Modulation of mechanical properties in multiple-component tissue adhesives.
AB - In vitro, ex vivo, and in vivo studies were performed to investigate the effect
of mixing upon the mechanical properties of a two-component tissue adhesive. The
hypothesis investigated was that a more complete mixing of the two components
would yield an increase in the mechanical performance of the adhesive. This in
turn would be demonstrated by improved outcomes in models of clinical sealant
application. In vitro stereological analysis of tissue adhesive mixed and
delivered by several different applicators demonstrated variation in the amount
of mixing provided by each type of delivery system. Ex vivo tensile adhesive
strength showed that there was a correlation between the amount of mixing and
bonding strength; that is, more thorough mixing demonstrated higher adhesive
strength. No significant difference was seen, however, between the different
applicator types and impact on in vivo dermal incisional closure strength. There
was a correlation, though, in amount of mixing and in vivo hemostasis. In a
rabbit spleen incision model, a more thoroughly mixed sealant corresponded with a
decrease in time to obtain complete hemostasis, as well as less sealant used. The
effects of mixing on tissue-adhesive mechanical performance were influenced
somewhat by the amount of mixing provided by the applicator. This effect,
however, was dependent upon the sealant formulation and the type of in vivo
application.
PMID- 11007623
TI - The influence of transforming growth factor beta1 on mesenchymal cell repair of
full-thickness cartilage defects.
AB - To repair full-thickness articular cartilage defects in rabbit knees, we
transplanted periosteal cells in a fibrin gel and determined the influence of
transforming growth factor beta (TGF-beta) in vitro. Alginate served as a
temporary supportive matrix component and was removed prior to transplantation.
The defects were analyzed macroscopically, histologically, and electron
microscopically, and evaluated with a semi-quantitative score system. Periosteal
cell transplants showed a chondrogenic differentiation, which results in the
development of embryonic-like cartilage tissue after 4 weeks and complete
resurfacing of the patellar groove after 12 weeks. In the control groups, no
repair was observed. Under the influence of TGF-beta1 we observed a reduction of
the cartilage layer, whereas the osteochondral integration and the zonal
architecture were improved. Periosteal cell-beads are stable cartilage
transplants and have stiffness and elasticity enough for easy and sufficient
transplant fixation. Further investigations are necessary to optimize the
application of TGF-beta1 for cartilage repair.
PMID- 11007624
TI - Bioactive macroporous titanium surface layer on titanium substrate.
AB - A macroporous titanium surface layer is often formed on titanium and titanium
alloy implants for morphological fixation of the implants to bone via bony
ingrowth into the porous structure. The surface of titanium metal was recently
shown to become highly bioactive by being subjected to 5.0 M-NaOH treatment at 60
degrees C for 24 h and subsequent heat treatment at 600 degrees C for 1 h. In the
present study, the NaOH and heat treatments were applied to a macroporous
titanium surface layer formed on titanium substrate by a plasma spraying method.
The NaOH and heat treatments produced an uniform amorphous sodium titanate layer
on the surface of the porous titanium. The sodium titanate induced a bonelike
apatite formation in simulated body fluid at an early soaking period, whereby the
apatite layer grew uniformly along the surface and cross-sectional macrotextures
of the porous titanium. This indicates that the NaOH and heat treatments lead to
a bioactive macroporous titanium surface layer on titanium substrate. Such a
bioactive macroporous layer on an implant is expected not only to enhance bony
ingrowth into the porous structure, but also to provide a chemical integration
with bone via apatite formation on its surface in the body.
PMID- 11007625
TI - Possible explanation for the white band artifact seen in clinically retrieved
polyethylene tibial components.
AB - Studies have focused attention on the appearance of a subsurface white band in
clinically retrieved polyethylene components and the possible contribution of
this phenomenon to early polyethylene delamination. Unconsolidated polyethylene
particles and oxidation have been suggested as possible reasons for the
appearance of the white band. Calcium stearate and other additives used in
processing ultra-high molecular weight polyethylene may also contribute to
formation of the white band. A quantitative investigation was conducted on 11
retrieved tibial components that exhibited a subsurface white band to determine
whether the amount of calcium stearate particles and additives were greater in
the white band region when compared with the mid-portion of the same section of
polyethylene. Calcium stearate particles and other additives were quantified
using backscattered electron imaging with correlated elemental analysis. The
particles were identified based on morphology and elemental patterns similar to
reference calcium stearate particles and known additives. Significantly more (p <
0. 0001) calcium stearate particles and additives were present in the white band
region (4578 +/- 418 particles/mm(2); mean +/- standard error) than the mid
portion region (1250 +/- 147 particles/mm(2)) of the sectioned tibial inserts.
The percent area occupied by calcium stearate particles and additives was five
times higher (p < 0.0001) within the white band region (0.81 +/- 0.10%) than the
mid-portion region (0.16 +/- 0.03%). The increased presence of calcium stearate
and other additives in the white band region suggests that they may play a role
in the formation of the white band. In future investigations it may be important
to consider how calcium stearate and other additives in polyethylene resins
affect white band formation and the possible contribution to crazing, early
delamination, and osteolysis in total joint replacement.
PMID- 11007626
TI - Adsorption of peroxidase on titanium surfaces: A pilot study.
AB - The present study demonstrates the in vitro and in vivo adsorption of peroxidase
onto titanium surfaces. Titanium foils (mean +/- SEM: 365 +/- 2 mm(2), n = 114)
were incubated during 30 min with lactoperoxidase (4 mg in 5 mL 100 mM phosphate
buffer pH 7). After 15 washings by H(2)O, titanium foils were incubated with o
phenylenediamine (6 mg/mL) and H(2)O(2) (7 mM) during 30 min. The reaction was
then stopped by the addition of HCI 1M and the absorbance of the liquid phase was
read on a spectrophotometer at 492 nm. In vitro adsorbed lactoperoxidase onto
titanium surfaces was 0.70 +/- 0.05 ng/mm(2) (mean +/- SEM, n = 30). X-ray
photoelectron spectroscopy confirmed the incorporation of protein nitrogen onto
titanium surfaces: the nitrogen atomic percentage increased from 0.9 +/- 0.3 to
12.7 +/- 0.2% (n = 3) and from 3.7 +/- 0.1 to 14.4 +/- 0. 4% (n = 5) when
titanium foils were incubated in the lactoperoxidase solution during 30 min and
24 h respectively. In vivo, oral peroxidases adsorbed on titanium healing
abutments from 0.01 to 0.58 ng/mm(2) (n = 19) after 2 weeks in the oral
environment.
PMID- 11007627
TI - Effect of vapor-flame treatment on plasma sprayed hydroxyapatite coatings.
AB - A vapor-flame treatment was developed to modify the crystallinity of the as
sprayed hydroxyapatite (HA) coatings. The effects of the treatment on
composition, structure, and properties of HA coatings were investigated. Results
showed that the vapor-flame treatment is simple and efficient to adjust the
crystallinity of as-sprayed HA coating. Its crystallinities can be raised from
53.5 to 98.7% in 3-7 min. The porosities of coatings increased with an increase
in the vapor-flame treating time. The microhardness of coating decreased as a
result of this treatment. It may be explained in terms of the extent of
microcracks caused by recrystallization of amorphous HA and relaxation of stress
of the coating. The porosity, bonding strength, and hardness of HA coatings
treated for 7 min were 15.7%, 32.0 MPa (300 microm thickness), and 1.9 GPa,
respectively.
PMID- 11007628
TI - Comparative study of seeding methods for three-dimensional polymeric scaffolds
PMID- 11007629
TI - Total intravenous anesthesia with midazolam, remifentanil, propofol and
cistracurium in morbid obesity.
AB - BACKGROUND: According to physical impairments of massive obesity, cardiac,
respiratory and gastrointestinal physiology must be considered as much as
pharmacokinetic behavior. Anesthetic management of morbidly obese patients has to
be carefully planned, in order to minimize the increased risks of aspirative
pneumonitis, hemodynamic instability and delay in recovery. The ideal anesthesia
should provide a smooth and quick induction, allowing rapid airway control,
prominent hemodynamic stability, and rapid emergence from anesthesia. To approach
these ideal conditions, a Total Intravenous Anesthesia (TIVA) with midazolam,
remifentanil, propofol and cisatracurium was designed and analyzed. METHODS: 10
consenting morbidly obese patients scheduled for elective Laparoscopic Adjustable
Gastric Banding participated in the study. TIVA with midazolam, remifentanil,
propofol and cisatracurium was used in all cases. Time to loss of consciousness,
tracheal intubation, perianesthetic physiological parameters and complications,
incidence of awareness with recall, recovery times, postoperative analgesia and
costs of drugs were evaluated. RESULTS: The analyzed data showed adequate time
and physiological conditions for induction and tracheal intubation, stable
maintenance with easy handling of deepness, low incidence of perianesthetic
complications, excellent recovery performance and institutional efficiency.
CONCLUSIONS: TIVA with midazolam, remifentanil, propofol and cisatracurium was
found to be effective, secure, predictable and economic for the anesthetic
management of morbidly obese patients.
PMID- 11007630
TI - Laparoscopic Roux-en-Y gastric bypass: transoral or transgastric anvil placement?
AB - BACKGROUND: Laparoscopic techniques have been used to perform the Roux-en-Y
gastric bypass (RYGBP). The gastrojejunostomy may be constructed using an end-to
end anastomosis (EEA) stapler. Most reports describe passing the EEA anvil
transorally using an esophagogastroscope and a pull-wire technique. METHOD: We
describe problems experienced using this technique and present an alternative
method. RESULTS: Esophageal injury may occur during laparoscopic RYGBP (LRYGBP)
using the transoral anvil placement technique. When the anvil is retrieved into
the gastric pouch, the anvil may become lodged at the cricopharngeus muscle.
Dislodgment can be problematic and time-consuming. We present a case of mild
esophageal injury which occurred during transoral anvil placement. The patient
had transient postoperative dysphagia and recovered without sequelae. We present
an alternative method in which the anvil is passed through a gastrotomy.
CONCLUSION: Transgastric anvil placement alleviates the need for endoscopy,
thereby saving time and resources. This technique eliminates the potential for
esophageal injury. The transgastric anvil placement technique has proven
reliable. The transgastric method may make the LRYGBP operation safer and easier
to perform.
PMID- 11007631
TI - Silastic ring vertical gastroplasty by minilaparotomy.
AB - BACKGROUND: The incision length has significant influence on the postoperative
course after silastic ring vertical gastroplasty (SRVG). METHODS: A technique is
described in which SRVG can be performed through a minilaparotomy incision.
RESULTS: 110 patients were operated with this technique during 1996. No
remarkable intraoperative or postoperative complications were encountered.
Postoperative weight loss has been satisfactory. CONCLUSIONS: Performance of SRVG
through a minilaparotomy is feasible. The technique is recommended for surgeons
familiar with the operation through the formal incision.
PMID- 11007632
TI - Laparoscopic silicone adjustable gastric band: initial experience in finland.
AB - BACKGROUND: The Swedish adjustable gastric band (SAGB) was introduced in 1985 and
rapidly gained popularity. Today more than 21,000 gastric banding procedures have
been performed in Europe. The reported results of gastric banding operations are
mainly good, although the method is not without controversies and risks. We
report here our initial experience with the SAGB. METHODS: 60 patients (44 women,
16 men) were treated surgically for morbid obesity between the years 1996 and
1999, with SAGB. Median age of the patients was 44 years (range 21-64) and
preoperative median Body Mass Index (BMI, kg/m(2)) was 45 (range 35-55). 3
patients were operated by an open approach, and the remaining 57
laparoscopically. RESULTS: Operative time was 62-206 minutes (median 97 minutes).
Only one operation was converted to open approach (1.8%), due to extensive
adhesions. No intraoperative complications occurred. At 1 year follow-up, mean
weight loss was 30 kg, mean excess weight loss was 50%, and median BMI was 35. 4
patients have been reoperated so far (6.7%) due to slippage of the band (2
patients), infection of the band (1 patient), and leaking of the filling system
(1 patient). Median postoperative hospital stay was 3 days (range 2-53).
Mortality was 0%. Immediate postoperative morbidity-rate was 12% (7/60), although
serious morbidity occurred in only 1 patient (1.7%). CONCLUSIONS:
Laparoscopically placed adjustable gastric band is a good option for the morbidly
obese patient.
PMID- 11007633
TI - Influence of metabolic state and diabetes on the outcome at the end of first year
after gastric banding.
AB - BACKGROUND: The influence of metabolic state and the presence of diabetes before
surgery on the weight changes following non-adjustable gastric banding, were
studied. METHODS: The total of 50 patients referred for gastric banding had the
following parameters measured: insulinemia, glycemia, total cholesterol,
triglycerides (TAG), dehydroepiandrostendione (DHEA) and its sulphate (DHEA-S),
triiodothyronine, thyroxine, and thyroxine-stimulating hormone. We evaluated 28
of these, who completed at least 6 months of follow-up. 12 of these patients had
diet-treated non-insulin dependent diabetes mellitus (NIDDM) and 16 were non
diabetics, and 9 of them had a positive family history of NIDDM (FH DM). We
compared the change in weight of the diabetics, non-diabetics and those with
positive FH DM, at 3, 6 and 12 months after the operation. Multiple linear
regression tested the influence of the measured parameters on patients' weight.
RESULTS: Weight loss was greatest in the group of patients without a positive
family history of diabetes, and lowest in the diabetic group. Due to the high
dispersion, differences in the t-test are not significant. When individual
factors and their influence on weight development were tested by multiple linear
regression, weight loss was greatest in patients with high TAG and low insulin
levels and lowest in patients with diabetes or positive FH DM. CONCLUSIONS:
Although post-operative weight can be influenced by other factors, eg.
psychological ones, it is advisable to test each patient pre-operatively for
insulin and TAG levels, and to establish family history of diabetes and presence
of diabetes to give an idea of the prognosis of weight change.
PMID- 11007634
TI - Laparoscopic gastric bypass: endostapler transoral or transabdominal anvil
placement.
PMID- 11007635
TI - Warning signals, receiver psychology and predator memory.
AB - This review identifies four receiver psychology perspectives that are likely to
be important in the design and evolution of warning signals. Three of these
perspectives (phobia, learning and prey recognition) have been studied in detail,
and I include a brief review of recent work. The fourth, a memory perspective,
has received little attention and is developed here. A memory perspective asks,
'how might warning signals function to reduce forgetting of avoidances between
encounters?'. To answer this question I review data from psychology literature
that describe important features of animal long-term memory. These data suggest
that components of warning signals may function to reduce forgetting (and
therefore increase memorability) by (1) preventing forgetting of learnt prey
discriminations; (2) jogging the memories of forgetful predators; and (3) biasing
forgetting in favour of prey avoidance when the warning signal of a defended
aposematic species is copied by an edible Batesian mimic. A combination of a
learning and a memory perspective suggests that the features of aposematic prey
that accelerate avoidance learning may also be the features that decelerate
forgetting processes. If correct, this would have important implications for the
comprehension of signal design. Finally, I suggest that the cryptic appearance of
an edible prey may decelerate predator learning and accelerate predator
forgetting, to the benefit of the prey. In terms of learning and memory, crypsis
may be an antisignal. Copyright 2000 The Association for the Study of Animal
Behaviour.
PMID- 11007636
TI - Re-expression of songs deleted during vocal development in white-crowned
sparrows, Zonotrichia leucophrys.
AB - White-crowned sparrows learn and produce multiple song types as juveniles, but
most individuals stop singing all except one by the end of the first singing
season. This single song type is generally maintained throughout adulthood. We
demonstrate that, at the start of the second and subsequent singing seasons, this
species can recall songs that had been deleted during the first singing season.
The re-expression of song occurred in both the oriantha and the gambelii
subspecies. Although all our males recrystallized the original song in the second
year, our results indicate a mechanism for seasonal song change without new song
memorization. The traditional dichotomy of closed-ended versus open-ended
learning is inadequate for birds that learn early in life but can change their
song output seasonally. We suggest that species can exhibit a closed sensitive
period for song memorization and first production, with the ability to recall
deleted songs later in life. This type of learning, selective attrition followed
by subsequent re-expression, may be used by some species currently considered
open-ended learners. Copyright 2000 The Association for the Study of Animal
Behaviour.
PMID- 11007637
TI - MHC-mediated fetal odourtypes expressed by pregnant females influence male
associative behaviour.
AB - Mice can recognize one another by individually characteristic phenotypic body
odours (odourtypes) that reflect their genetic constitution at the highly
polymorphic major histocompatibility complex (MHC) of genes on chromosome 17. We
have shown previously that MHC-determined odours are produced by fetuses: house
mice, Mus domesticus, can be trained to discriminate between genetically
identical pregnant females carrying 9-18-day-old fetuses of differing MHC type.
Theoretically, it should be possible for a mouse to determine the MHC type of the
sire based on the odourtype of the pregnant female. In the current study we
investigated whether untrained male mice show spontaneous discrimination between
such pregnant mice. In experiment 1, sexually inexperienced male mice spent more
time near pregnant females that carried fetuses most genetically different from
the males themselves. Experiment 2, designed to evaluate possible experiential
effects on this preference, tested males that were cohabiting and had impregnated
a female that was either genetically identical to the test male (excepting X and
Y chromosomes) or differed from him only at the MHC. Males in the former case
performed virtually identically to those tested in experiment 1. In contrast
males in the latter group did not display this preference. These studies reveal
that among untrained male mice, fetal MHC type influences choice behaviour
presumably via fetal odourtypes expressed in maternal secretions/excretions and
that previous housing and/or mating experience modulates male choice. Copyright
2000 The Association for the Study of Animal Behaviour.
PMID- 11007638
TI - A species-specific acoustic cue for selective song learning in the white-crowned
sparrow.
AB - Song learning in birds is paradoxical. Without tutoring, songbirds do not develop
normal songs. Yet despite this inability, birds possess extensive foreknowledge,
in a mechanistic sense, about the normal song of their species. When given a
choice of tape recordings, young, naive songbirds select sounds of their own
species for imitation. We tape-tutored white-crowned sparrows, Zonotrichia
leucophrys oriantha, with a set of manipulated songs to investigate whether the
introductory whistle universally present in white-crowned sparrow song guides
selective song learning in this species. Our results confirm that this whistle
serves as a cue for song learning, enabling acquisition of normally rejected
sounds of other species, including hermit thrush, Catharus guttatus, notes, which
have a sound quality distinct from that of natural white-crowned sparrow phrases.
Our results support the conclusion that sensory mechanisms rather than motor
constraints are primarily responsible for the selectivity seen in song learning.
Copyright 2000 The Association for the Study of Animal Behaviour.
PMID- 11007639
TI - Survival regression analysis: a powerful tool for evaluating fighting and
assessment.
AB - Theoretical models of animal contests frequently generate predictions about how
asymmetries (e.g. differences in size, residence status) between contestants
affect fight duration. Linear regression and nonparametric correlation analyses
are commonly used to test the fit of data to such models. We show how survival
regression analysis (SRA) is a powerful technique for studying the effect of
asymmetries on the duration of contests. SRA, which is under-utilized by students
of animal behaviour, offers several advantages over more frequently used
procedures. It provides unbiased parameter estimates even when including censored
data (i.e. results of contests that have not ended at the time when observations
are stopped). The analysis of hazard functions, which is a component of SRA, is
an easy way to test for consistency with predictions of the sequential assessment
game model. These and other advantages of SRA are illustrated by using SRA and
more conventional methods to analyse the effect of asymmetries on contest
duration for encounters between female Mediterranean tarantulas, Lycosa tarentula
(L.). It is hoped that this example of the advantages of SRA will encourage more
widespread use of this powerful technique. Copyright 2000 The Association for the
Study of Animal Behaviour.
PMID- 11007640
TI - Chemically mediated predator inspection behaviour in the absence of predator
visual cues by a characin fish.
AB - Animals commonly approach (i.e. 'inspect') potential predators. Glowlight tetras,
Hemigrammus erythrozonus, have previously been shown to inspect the combined
chemical and visual cues originating from novel predators and to modify their
inspection (approach) behaviour depending upon the predator's diet. We conducted
two experiments to determine whether tetras would inspect the chemical cues of
injured prey or the dietary cues of a novel predator in the absence of any visual
cues. Shoals of glowlight tetras were exposed to either distilled water (control)
or the skin extract of swordtail (lacking ostariophysan alarm pheromones) or the
skin extract of tetra (with alarm pheromones). There was no significant
difference in the frequency of predator inspection behaviour towards swordtail or
tetra skin extract compared to the distilled water controls. In the second
experiment, we exposed shoals of tetras to either distilled water or the odour of
Jack Dempsey cichlids, Cichlasoma octofasciatum, which had been food deprived, or
fed a diet of swordtails or tetras. There was no significant difference in the
frequency of predator inspection behaviour towards the odour of the starved
cichlids and the odour of the fed cichlids in either of the two diet treatments.
However, when tetras were exposed to the odour of cichlids fed tetras, they took
significantly longer to initiate an inspection visit, remained further from the
source of the chemical cues and inspected in smaller groups, compared with the
odour of a starved cichlid or a cichlid fed swordtails. These data strongly
suggest that tetras will inspect chemical cues alone, but only if the cue
contains information about the predator. Copyright 2000 The Association for the
Study of Animal Behaviour.
PMID- 11007641
TI - Mechanisms of maternal rank 'inheritance' in the spotted hyaena, Crocuta crocuta.
AB - Maternal rank 'inheritance', the process by which juveniles attain positions in
the dominance hierarchy adjacent to those of their mothers, occurs in both
cercopithecine primates and spotted hyaenas. Maternal rank is acquired in
primates through defensive maternal interventions, coalitionary support and
unprovoked aggression ('harassment') directed by adult females towards offspring
of lower-ranking individuals. Genetic heritability of rank-related traits plays a
negligible role in primate rank acquisition. Because the social lives of Crocuta
and cercopithecine primates share many common features, we examined whether the
same mechanisms might operate in both taxa to promote maternal rank
'inheritance'. We observed a large clan of free-living spotted hyaenas in Kenya
to test predictions of four mechanistic hypotheses. Hyaena rank acquisition did
not appear to be directly affected by genetic heritability. Unprovoked aggression
from adult female hyaenas was not directed preferentially towards low-ranking
cubs. However, high-ranking mothers intervened on behalf of their cubs more
frequently and more effectively than low-ranking mothers. Maternal interventions
and supportive coalitions appeared to reinforce aggression directed at
'appropriate' conspecific targets, whereas coalitionary aggression directed at
cubs apparently functioned to extinguish their aggressive behaviour towards
'inappropriate' targets. Young hyaenas and primates thus appear to 'inherit'
their mothers' ranks by strikingly similar mechanisms. Copyright 2000 The
Association for the Study of Animal Behaviour.
PMID- 11007642
TI - The influence of age and size on temporal mate signalling behaviour.
AB - I investigated how male size, condition and age influence both time spent calling
and how signals are apportioned throughout the night (i.e. temporal calling
pattern) in the Texas field cricket, Gryllus integer. I quantified male calling
time and temporal calling pattern using an electronic apparatus that continuously
monitored male calling/noncalling behaviour throughout the night. Male condition,
measured using the residuals from an allometric regression of male mass on
overall body size, did not explain any variation in either time spent calling or
temporal calling pattern. However, some intrapopulation variation in time spent
calling and temporal calling pattern was explained by differences in male size
and age. Large males called more often than small males. Young and very old adult
males called significantly less often than middle-age males. As males aged they
initiated calling earlier in the evening, probably increasing their
susceptibility to parasitism by the tachinid parasitoid Ormia ochracea. Overall,
age and size differences explained 10-40% of signalling variation in male G.
integer. Copyright 2000 The Association for the Study of Animal Behaviour.
PMID- 11007643
TI - Experimental evidence that group foragers can converge on predicted producer
scrounger equilibria.
AB - When foraging together, animals are often observed to feed from food discoveries
of others. The producer-scrounger (PS) game predicts how frequently this
phenomenon of food parasitism should occur. The game assumes: (1) at any moment
all individuals can unambiguously be categorized as either playing producer
(searching for undiscovered food resources) or scrounger (searching for
exploitation opportunities), and (2) the payoffs received from the scrounger
tactic are negatively frequency dependent; a scrounger does better than a
producer when the scrounger tactic is rare, but worse when it is common. No study
to date has shown that the payoffs of producer and scrounger conform to the
game's assumptions or that groups of foragers reach the predicted stable
equilibrium frequency (SEF) of scrounger, whereby both tactics obtain the same
payoff. The current study of three captive flocks of spice finches, Lonchura
punctulata, provides the first test of the PS game using an apparatus in which
both assumptions of the PS game are met. The payoffs to the scrounger, measured
as feeding rate (seeds/s), were highly negatively frequency dependent on the
frequency of scrounger. The feeding rate for scrounger declined linearly while
the rate for producer either declined only slightly or not at all with increasing
scrounger frequency. When given the opportunity to alternate between tactics, the
birds changed their use of each, such that the group converged on the predicted
SEF of scrounger after 5-8 days of testing. Individuals in this study, therefore,
demonstrated sufficient plasticity in tactic use such that the flock foraged at
the SEF of scrounger. Copyright 2000 The Association for the Study of Animal
Behaviour.
PMID- 11007644
TI - Using video playbacks to study visual communication in a marine fish, Salaria
pavo.
AB - Video playbacks have been successfully applied to the study of visual
communication in several groups of animals. However, this technique is
controversial as video monitors are designed with the human visual system in
mind. Differences between the visual capabilities of humans and other animals
will lead to perceptually different interpretations of video images. We
simultaneously presented males and females of the peacock blenny, Salaria pavo,
with a live conspecific male and an online video image of the same individual.
Video images failed to elicit appropriate responses. Males were aggressive
towards the live male but not towards video images of the same male. Similarly,
females courted only the live male and spent more time near this stimulus. In
contrast, females of the gynogenetic poecilid Poecilia formosa showed an equal
preference for a live and video image of a P. mexicana male, suggesting a
response to live animals as strong as to video images. We discuss differences
between the species that may explain their opposite reaction to video images.
Copyright 2000 The Association for the Study of Animal Behaviour.
PMID- 11007645
TI - Individual mares bias investment in sons and daughters in relation to their
condition.
AB - The Trivers-Willard hypothesis (TWH) predicts that a mother will treat a son or
daughter differently depending on her ability to invest and the impact of her
investment on offspring reproductive success. Although many studies have
investigated the hypothesis, few have definitively supported or refuted it
because of confounding factors or an inappropriate level of analysis. We studied
maternal investment in sons and daughters in feral horses, Equus caballus, which
meet the assumptions of the TWH with a minimum of confounding variables.
Population level analyses revealed no differences in maternal behaviour towards
sons and daughters. When we incorporated mare condition, we found that sons were
more costly to mares in good condition, whereas daughters were more costly to
mares in poor condition, although no differences in maternal behaviour were
found. However, since the TWH makes predictions about individual mothers, we
examined investment by mares who reared both a son and a daughter in different
years of the study. Mares in good condition invested more in their sons in terms
of maternal care patterns, costs to maternal body condition and costs to future
reproduction. Conversely, mares in poor condition invested more in daughters.
Therefore, with an appropriate level of analysis in a species in which
confounding variables are minimal, the predictions of the Trivers-Willard
hypothesis are supported. Copyright 2000 The Association for the Study of Animal
Behaviour.
PMID- 11007646
TI - Diet of a polyphagous arthropod predator affects refuge seeking of its thrips
prey.
AB - Antipredator behaviour of prey costs time and energy, at the expense of other
activities. However, not all predators are equally dangerous to all prey; some
may have switched to feeding on another prey species, making them effectively
harmless. To minimize costs, prey should therefore invest in antipredator
behaviour only when dangerous predators are around. To distinguish these from
harmless predators, prey may use cues related to predation on conspecifics, such
as odours released by a predator that has recently eaten conspecific prey or
alarm pheromones released by attacked prey. We studied refuge use by a
herbivorous/omnivorous thrips, Frankliniella occidentalis, in response to odours
associated with a generalist predatory bug, Orius laevigatus, fed either with
conspecific thrips or with other prey. The refuge used by thrips larvae is the
web produced by its competitor, the two-spotted spider mite, Tetranychus urticae,
where thrips larvae experience lower predation risk because the predatory bug is
hindered by the web. Thrips larvae moved into this refuge when odours associated
with predatory bugs that had previously fed on thrips were present, whereas
odours from predatory bugs that had fed on other prey had less effect. We discuss
the consequences of this antipredator behaviour for population dynamics.
Copyright 2000 The Association for the Study of Animal Behaviour.
PMID- 11007647
TI - Effect of maternal and paternal line on spatial and temporal marine distribution
in Atlantic salmon.
AB - We examined the inheritance of the sea migration pattern of Atlantic salmon,
Salmo salar, in a crossing and tagging experiment in the Baltic Sea. Individuals
from the parental stocks, Neva and Iijoki, and their reciprocal hybrids were
released as 2-year-old smolts, into the same estuary of the Bothnian Sea in 1994.
Two thousand smolts from each of the four groups were marked with Carlin tags.
The recapture rate of the tags was nearly 10%. We used log-linear models to
analyse the marine distribution of the salmon groups from the tag recovery data.
The pure stocks and their pooled hybrid groups all showed statistically
significant differences between each other in spatial and temporal sea
distribution. The Iijoki salmon were more frequently (9%) caught outside the
Bothnian Sea than were the Neva salmon (2%). The majority of the Iijoki salmon
(55%), but fewer Neva salmon (40%), were caught in the second sea year. In
spatial distribution, the hybrids seemed to be intermediate between the parental
stocks, with no differences between reciprocal female and male lines. In duration
of sea migration and age at maturity, however, the hybrids were very similar to
their maternal line, the effect of which was thus clearly stronger than that of
the paternal line. Copyright 2000 The Association for the Study of Animal
Behaviour.
PMID- 11007648
TI - Diversity of behaviour during novel object tests is reduced in pigs housed in
substrate-impoverished conditions.
AB - Modern intensive farming conditions lack the diversity of substrates present in
more natural environments and offer young animals fewer opportunities for
interaction. Evidence exists that this may affect the organization of interactive
patterns of behaviour, but shifts in behavioural diversity have not been measured
directly. We investigated the effect of the substrate in the home pen on the
diversity of behaviour in young growing pigs, Sus scrofa. Over 5 months, 26 pigs
were housed singly in either substrate-impoverished (SI) or substrate-enriched
(SE) conditions. Once every month we recorded the behaviour of these pigs in
detail both in the home pens and in two novel object tests. In addition, we
calculated the diversity of behaviour shown by SI and SE pigs in the home pen and
in the novel object tests, using a relative behavioural diversity index. In the
two novel object tests, SI pigs were less mobile than SE pigs and focused their
behaviour on particular substrates. In addition, SI pigs showed less diverse
behaviour than SE pigs. Our results show that the less diverse behaviour of SI
pigs previously recorded in their home pens persists under novel conditions,
supporting the hypothesis that substrate-impoverished housing conditions
structurally affect the organization of behaviour in young growing pigs.
Copyright 2000 The Association for the Study of Animal Behaviour.
PMID- 11007649
TI - Individual food-hoarding decisions in a nonterritorial coal tit population: the
role of social context.
AB - Among the Paridae, food hoarding is thought to be strongly associated with the
exclusive use of territories by winter groups, although it has also been
described in populations with loose social systems. However, detailed data on
such populations are scarce. To identify the mechanisms underlying individual
storing decisions, I studied hoarding behaviour in a nonterritorial, high-density
coal tit, Parus ater, population in a subalpine forest. The presence of close
neighbours (within 5 m) had the strongest, negative influence on caching
probability, whereas more distant neighbours foraging in the same flock did not
affect the probability of caching. Adults concentrated their stores in the centre
of their home ranges. Caching location, but not caching intensity, was affected
by the time of day. Coal tits took longer, and travelled further, to cache food
in the inner parts of trees than in the outer parts. Resident adults stored in
inner, safer caching locations more often than juvenile residents and transients.
Differences in hoarding effort according to the storing substrate, and the daily
storing location pattern of juvenile residents and transients, suggest that
stores have a different use depending on where they are located. Therefore, my
results show that hoarding is compatible with a nonterritorial, nonbreeding
social system; hoarding could thus have originated in an ancient, nonterritorial,
but sedentary, tit species. Copyright 2000 The Association for the Study of
Animal Behaviour.
PMID- 11007650
TI - Pigs shift too: foraging strategies and spatial memory in the domestic pig.
AB - In a previous experiment, we showed that domestic pigs, Sus scrofa, unlike many
other species, performed accurately in a spatial memory task, where visits to a
previously baited food trough were rewarded (win-stay). We investigated whether
pigs have a predisposition for this strategy, by comparing their performance in a
radial arm maze under either win-stay (N=10) or win-shift (N=10) reward
contingencies. Contrary to our earlier results, only one of the animals in the
win-stay condition was able to reach the imposed criterion level of accuracy. The
performances of the other win-stay pigs did not deviate from random. All pigs in
the win-shift condition reached criterion by day 25 of the experiment, and
performed better than expected by chance. Analysis of the types of errors made
matched our a priori predictions that shift movements would occur more
frequently, especially within visits to the maze. We suggest that the difference
in learning rates may reflect the fact that win-stay pigs needed to use two
different rules, stay between trials and shift within trials, while win-shift
pigs only needed to use the shift rule. In our previous study, win-stay pigs did
not experience a conflict of rules and this may have facilitated stay learning.
We found evidence of a recency effect in win-shift animals and a primacy effect
in the win-stay group. However, we discuss the unsuitability of these specific
terms in this type of experiment, and propose an alternative interpretation of
the results. Copyright 2000 The Association for the Study of Animal Behaviour.
PMID- 11007651
TI - Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in
complex with pterin monophosphate: new insight into the enzymatic mechanism and
sulfa-drug action.
AB - The enzyme 7,8-dihydropteroate synthase (DHPS) catalyzes the condensation of para
aminobenzoic acid (pABA) with 6-hydroxymethyl-7, 8-dihydropterin-pyrophosphate to
form 7,8-dihydropteroate and pyrophosphate. DHPS is essential for the de novo
synthesis of folate in prokaryotes, lower eukaryotes, and in plants, but is
absent in mammals. Inhibition of this enzyme's activity by sulfonamide and
sulfone drugs depletes the folate pool, resulting in growth inhibition and cell
death. Here, we report the 1.7 A resolution crystal structure of the binary
complex of 6-hydroxymethylpterin monophosphate (PtP) with DHPS from Mycobacterium
tuberculosis (Mtb), a pathogen responsible for the death of millions of human
beings each year. Comparison to other DHPS structures reveals that the M.
tuberculosis DHPS structure is in a unique conformation in which loop 1 closes
over the active site. The Mtb DHPS structure hints at a mechanism in which both
loops 1 and 2 play important roles in catalysis by shielding the active site from
bulk solvent and allowing pyrophosphoryl transfer to occur. A binding mode for
pABA, sulfonamides and sulfones is suggested based on: (i) the new conformation
of the closed loop 1; (ii) the distribution of dapsone and sulfonamide resistance
mutations; (iii) the observed direction of the bond between the 6-methyl carbon
atom and the bridging oxygen atom to the alpha-phosphate group in the Mtb
DHPS:PtP binary complex; and (iv) the conformation of loop 2 in the Escherichia
coli DHPS structure. Finally, the Mtb DHPS structure reveals a highly conserved
pterin binding pocket that may be exploited for the design of novel
antimycobacterial agents.
PMID- 11007652
TI - Pitfalls in homozygosity mapping.
AB - There is much interest in use of identity-by-descent (IBD) methods to map genes,
both in Mendelian and in complex disorders. Homozygosity mapping provides a rapid
means of mapping autosomal recessive genes in consanguineous families by
identifying chromosomal regions that show homozygous IBD segments in pooled
samples. In this report, we point out some potential pitfalls that arose during
the course of homozygosity mapping of the enhanced S-cone syndrome gene,
resulting from (1) unexpected allelic heterogeneity, so that the region
containing the disease locus was missed as a result of pooling; (2)
identification of a homozygous IBD region unrelated to the disease locus; and (3)
the potential for inflation of LOD scores as a result of underestimation of the
extent of inbreeding, which Broman and Weber suggest may be quite common.
PMID- 11007653
TI - Chromosomal duplication involving the forkhead transcription factor gene FOXC1
causes iris hypoplasia and glaucoma.
AB - The forkhead transcription factor gene FOXC1 (formerly FKHL7) is responsible for
a number of glaucoma phenotypes in families in which the disease maps to 6p25,
although mutations have not been found in all families in which the disease maps
to this region. In a large pedigree with iris hypoplasia and glaucoma mapping to
6p25 (peak LOD score 6.20 [recombination fraction 0] at D6S967), no FOXC1
mutations were detected by direct sequencing. However, genotyping with
microsatellite repeat markers suggested the presence of a chromosomal duplication
that segregated with the disease phenotype. The duplication was confirmed in
affected individuals by FISH with markers encompassing FOXC1. These results
provide evidence of gene duplication causing developmental disease in humans,
with increased gene dosage of either FOXC1 or other, as yet unknown genes within
the duplicated segment being the probable mechanism responsible for the
phenotype.
PMID- 11007654
TI - Commentary. monitoring tobacco use in canada: the need for a surveillance
strategy.
AB - Smoking behaviour has been monitored nationally through population surveys for 35
years in Canada, but these surveys have not been as consistent or rigorous as the
magnitude of the smoking problem demands. Inconsistent methods and irregular
survey intervals are just two of the characteristics that have made it difficult
to know exactly how smoking is changing. Further, an absence of routine data on
tobacco control policies (other than the price of cigarettes) has hampered
understanding of the determinants of changing prevalence. The advent of two
survey series--Canadian Tobacco Use Monitoring Survey (CTUMS) and Canadian
Community Health Survey (CCHS) promises to change this situation for the better.
We suggest that both are critical elements of a national smoking surveillance
system and that, with a commitment to CTUMS in particular, Health Canada could
set a new international standard for surveillance.
PMID- 11007655
TI - Predictors of smoking cessation in an incentive-based community intervention.
AB - The Quit and Win Challenge, an incentive-based intervention, was implemented in
two counties in Eastern Ontario to encourage adult smokers to quit smoking.
Participants (n = 231) were compared with adult smokers selected at random (n =
385) from a larger, four-county area. Baseline characteristics were assessed by
telephone interview, including socio-demographic and smoking-related factors.
Follow-up interviews were also conducted by telephone. Initial and follow-up
response rates were high (over 84%) in both groups. Compared with the random
survey group, Quit and Win participants tended to be younger, more educated,
employed and heavier smokers, with fewer friends or co-workers who smoked. After
one year, 19.5% of them reported that they were smoke-free, whereas less than 1%
of the random group had achieved cessation. This translates into an impact rate
of 0.17%, affecting 1 in 588 adult smokers. With the exception of the smokers'
baseline "stage of change," none of the socio-demographic or smoking factors was
predictive of cessation. We conclude that this intervention achieved only limited
success and attracted certain sectors of the community disproportionately, i.e.
smokers who were highly motivated to quit. We argue that increased access to
proven cessation therapies would improve the impact of such interventions.
PMID- 11007656
TI - School-based smoking prevention: economic costs versus benefits.
AB - The objective of this study was to conduct a cost-benefit analysis to compare the
costs of developing and delivering an effective school-based smoking prevention
program with the savings to be expected from reducing the prevalence of smoking
in the Canadian population over time. A smoking prevention program that meets
published criteria for effectiveness, implemented nationally in Canada, would
cost $67 per student (1996 dollars). Assuming such a program would reduce smoking
by 6% initially and 4% indefinitely, lifetime savings on health care would be
$3,400 per person and on productivity, almost $14,000. The benefit-cost ratio
would be 15.4 and the net savings $619 million annually. Sensitivity analyses
reveal that considerable economic benefits could accrue from an effective smoking
prevention program under a wide range of conditions.
PMID- 11007657
TI - Performance of the composite international diagnostic interview short form for
major depression in a community sample.
AB - Recently, short-form versions of structured psychiatric diagnostic interviews
have been developed for epidemiologic and survey research. These short forms can
reduce research costs in large-scale studies; however, their accuracy is likely
to be less than that of a full diagnostic interview. We evaluated the positive
and negative predictive values of a short-form interview derived from the
Composite International Diagnostic Interview (CIDI). Samples of subjects who
scored both positively (n = 277) and negatively (n = 136) on the CIDI Short Form
for Major Depression (CIDI-SFMD) were administered the full depressive disorders
section of the CIDI. Almost all subjects who were negative on the short form were
similarly classified as not having major depression by the CIDI. Approximately
25% of subjects had false positive results; these subjects tended to be older and
less educated than true positives. Approximately 75% of subjects scoring five or
more on the CIDI-SFMD had major depression according to the full CIDI, and a
proportion of the remainder had less severe depressive syndromes. Some CIDI- SFMD
positive subjects may have had depressive symptoms attributable to organic or
other etiologies excluded under the definition of major depression.
PMID- 11007658
TI - Health-adjusted life expectancy at the local level in ontario.
AB - Health expectancy measures are becoming a common method of combining information
on mortality and health-related quality of life into one summary population
health measure. However, health expectancy measures are infrequently measured at
the local level, despite a shift toward health service planning to that level.
Using a modified Sullivan method, we calculated health-adjusted life expectancy
(HALE) for the 42 public health units in Ontario using life tables that were
derived from mortality and population data for 1988-1992 and the Health Utilities
Index from the 1990 Ontario Health Survey. There were large variations among
health units in HALE at age 15 for both men (range: 51.3-58.2 years) and women
(range: 56.6-62.9 years). Generally, rural and northern areas had the lowest
HALE. Local differences in male HALE were greater than for life expectancy (7.1
versus 6.0 years). Despite a relatively large health survey (45,583 respondents,
range: 729-1,746 per health unit), few HALE differences deviated significantly
from the Ontario mean, raising concerns about the feasibility of estimating local
health expectancy measures with adequate precision. Nevertheless, the wider local
differences and different geographic distribution of local HALE compared with
mortality measures, along with the additional benefit of being able to model the
complex interaction of mortality and morbidity, suggest that HALE may be a useful
population health measure.
PMID- 11007661
TI - [ [In Process Citation]
PMID- 11007659
TI - Ontario familial colon cancer registry: methods and first-year response rates.
AB - The Ontario Familial Colon Cancer Registry (OFCCR) is a novel registry that
collects family history information, epidemiologic data, blood samples and tumour
specimens from a population-based sample of colorectal cancer patients and their
families. Families are classified as either high familial risk, intermediate
familial/other risk or low (sporadic) risk for colorectal cancer. Obtaining high
response rates in genetic family studies is especially challenging because of
both the time commitment required and issues of confidentiality. The first-year
response rate was 61%, resulting in 1,395 participating probands. In an attempt
to assess potential response bias, we compared participants with non
participants. The age and sex of participants did not differ from non
participating probands; however, cases in rural areas were somewhat more likely
to participate. To date, 57% of 1,587 relatives participated; females were more
likely to participate, and relatives of low familial risk were least likely to
participate. The OFCCR is an excellent resource that will facilitate the study of
genetic and environmental factors associated with colorectal cancer.
PMID- 11007662
TI - [Thrombus remodeling. Key factor in the progression of coronary atherosclerosis].
AB - The mechanism of the progression of atherosclerosis involves the rupture of a
plaque with thrombus formation, followed by an invasion of monocytes that induce
the formation of tissue factor and a second thrombus. This is followed by
activation of the smooth muscle cells of the arterial wall with formation of
connective tissue that infiltrates both thrombi. We can try to prevent
atherosclerosis progression by inhibiting thrombosis with an inhibitor of tissue
factor, inhibiting the process of scarring with Rapamycin, or both. Nowadays, we
can study these processes using highly sensitive techniques to monitorize the
formation and evolution of the thrombus, and magnetic resonance imaging that
allow us to study the growth of the connective tissue. With these techniques we
can study the natural history of atherosclerosis and the efficacy of different
drugs to prevent its progression.
PMID- 11007663
TI - [Biochemical diagnosis of hypertensive myocardial fibrosis].
AB - A substantial increase in fibrillar collagen has been observed in the left
cardiac ventricle of animals and humans with arterial hypertension. Hypertensive
myocardial fibrosis is the result of both increased collagen types I and III due
to the fact that its synthesis by fibroblasts and myofibroblasts is stimulated
and its extracellular collagen degradation unchanged or decreased extracellular
collagen degradation. Hemodynamic and non-hemodynamic factors may be involved in
the disequilibrium between collagen synthesis and degradation that occurs in
hypertension. As shown experimentally and clinically, an exaggerated rise in
fibrillar collagen content promotes abnormalities of cardiac function,
contributes to the decrease in coronary reserve and facilitates alterations in
the electrical activity of the left ventricle. Although microscopic examination
of cardiac biopsies is the most reliable method for documenting and measuring
myocardial fibrosis, the development of non-invasive methods to indicate the
presence of myocardial fibrosis in hypertensive patients would be useful. We have
therefore applied a biochemical method based on the measurement of serum peptides
derived from the tissue formation when synthesized and degradation of fibrillar
collagens to monitor the turnover of these molecules in rats with spontaneous
hypertension and patients with essential hypertension.
PMID- 11007664
TI - [Heart failure: the electrophysiological connection. Myocardial stunning and
heart failure: mechanisms in common?].
AB - The delayed recovery of function after brief episodes of ischemia is known as
stunning. Myocardial stunning and heart failure would, at first glance, appear to
have little in common other than the obvious contractile dysfunction in both
settings. Here I describe studies which shed new light on the underlying
mechanisms of these two forms of contractile dysfunction, revealing unexpected
fundamental similarities.
PMID- 11007665
TI - [Dilated cardiomyopathy: recent advances and current treatment].
AB - The combination of dilatation and systolic dysfunction of the left or both
ventricles from idiopathic or specific origin define dilated cardiomyopathy (DC).
It is an important cause of cardiac morbidity through congestive heart failure
(CHF) or arrhythmias. Prevalence studies estimate a rate of left ventricular
systolic dysfunction of 2% to 3% or more, and of 1.5% of CHF among the general
population. Genetic studies on familial DC have identified at least 5 genetic
locus. In addition, the role of virus, genetic abnormalities, immunologic
responses and increased myocardial apoptosis are factors recognized factors that
play a significant role in the pathogenesis of idiopathic DC. Mortality in severe
CHF may reach 50% at 2 years after diagnosis. The introduction of "triple"
therapy combining diuretics, digoxin and angiotensin converting enzyme inhibitors
(ACEI) has significantly decreased this high mortality. Recent large,
multicentric clinical trials on drugs aimed to diminish the neuroendocrine
hyperactivity of patients in stable chronic CHF (betablockers and spirolactone)
have resulted in an additional reduction in total mortality of about 35% in
relation with control groups. Betablockers, compared to ACEI, also diminish the
rate of sudden death prompting their almost mandatory indication in the absence
of contraindications. Cardiac transplantation presently offers a survival rate of
66% at 5 years but donor scarcity has stabilized the number of procedures. In
patients resuscitated from malignant arrhytmias the implantation of
defibrillators offers a better survival than drugs. Future advances in the
knowledge of the pathogenesis and especially of genetic mechanisms, may
substantially change the understanding and treatment of these disorders.
PMID- 11007666
TI - [Aortic valve replacement with pulmonary autograft (the Ross procedure) in adult
and pediatric patients].
AB - Aortic valve replacement with pulmonary autograft was first performed by Donald
Ross in 1967. Initially, the procedure was not widely accepted, by Cardiologists
and Cardiac surgeons fundamentally due to its complexity and demanding surgical
technique, and because innumerous series two cardiac valves were at risk. The
results published in the last 10-15 years established the pulmonary autograft as
one of the best methods of aortic valve replacement, especially in pediatric
patients and young adults. In the present article, we reviewed present
indications and contraindications, and our clinical experience with 26 patients
(pediatrics and adults). Analysis of the first 22 the patients with a minimum of
6 months of follow-up (180-620 days) was performed. Follow-up is complete (100%).
Mean age was 31.4 +/- 12.6 years. Five patients were pediatrics (<= 14 years).
Three patients (11%) with previous percutaneous procedures and 4 patients (14%)
with previous surgical procedures. There was no early or late mortality. In the
last follow-up, 19 of 22 (86.36%) had no autograft insufficiency (>= grade 1),
and in one patient it was moderate (grade 2). The 2 remaining patients developed
severe autograft insufficiency (grade 4) and were reoperated on, with
satisfactory postoperative outcome. Mean maximal gradient was 7.85 +/- 5 mmHg at
18 months (3-29). Patients with preoperative aortic stenosis showed a significant
reduction in myocardial mass index (208.7 +/- 32 a 95.8 +/- 28.8 g/m2) at 18
months. In these patients, septal and posterior wall thickness decreased
significantly, in the first month. Two pediatric patients have developed
transpulmonar gradient > 50 mmHg. One of them underwent successful stent
implantation. We have not observed significant homograft insufficiency in any of
our patients. All our patients remain asymptomatic (functional class I) without
medical treatment. We have not observed either thromboembolic or haemorrhagic
episodes, nor endocarditis. No patient is receiving anticoagulants. Clinical and
echocardiographic mid term results in pulmonary autograft and homograft in our
series, are excellent after the Ross procedure.
PMID- 11007667
TI - [The heart transplantation in Spain. Organization and results].
AB - Heart transplantation has achieved a great development in Spain. With 8 heart
transplantation procedures per million of inhabitants per year, we are the second
ranking country, after the U.S.A., in this therapeutic activity. A relative
adequacy between the number of available donors and the number of receptors
included on the waiting list help to reduce the delays and the mortality rates in
expecting patients, compare to other countries, which demonstrated the efficiency
of the system. From 1984 to 1998, 2,756 heart transplantations were performed in
Spain, in 16 authorized hospitals. In 56 cases (2%) the procedures were re
transplantation. Cardiomyopathy with ischemic origin was the most frequent
pathology in determining the intervention, affecting to the 37% of the receptors,
followed by idiopathic dilated cardiomyopathy with a 35%. Compared to other
countries, a high proportion of cardiopathies (11%) of rheumatic origin stands
out.20% of the heart transplantations were performed in a maximum emergency
situation of the receptors. Assigning donors priority on a national scale. In a
2, 9% of the cases, extra procedures of circulatory assistance devises were used.
The actuarial survival of the whole series is 74% at the end of the first year;
62% after five years and 46% after ten years. The mean survival of the grafts was
9.5 years. These data do not differ substantially from those of the Registry of
the International Society of Heart and Lung Transplantation. The most important
causes of early mortality were the graft primary failure, the infections and the
rejection. Among the causes of late morbidity, cancer, with a prevalence of 6,1%,
and vascular disease of the graft, present in 8,4% of the receptors, stand out.
These results support the so-called Spanish Model for Solid Organ
Transplantation, which, according to the health authorities of the European
Union, should be implemented in all the member countries. The keys to the success
of the Spanish Model are based on three factors, in order of importance: a) to
have a public professionalized institution for the detection of donors, the
allocation of the grafts, and the coordination of the extraction and
transportation force. The Transplant National Organization is the name of this
complex force in our country; b) the high rates of road and labour mortality in
Spain, and c) to provide incentives for the professionals in charge of the whole
process.
PMID- 11007668
TI - Ethical selection of living kidney donors.
AB - Renal transplant centers vary markedly in their rates of living donor kidney
transplantation. Recent surveys also document marked differences among centers in
both appreciation of medical risk for donation and what constitutes ethical donor
selection. Because of this marked variability, some donors likely are being
inappropriately denied or others are being inappropriately accepted. In addition
to defensible donor education about risk and benefit, three fundamental
obligations of the center are identified: (1) to recognize that it is often
ethical to participate in acts of individual risk and sacrifice that are
performed to benefit others; (2) to not deny transplantation without good reason
to donors and recipients who apply to the center; and (3) to neutralize, but not
overreact to, center self-interest, which stems from the professional benefits of
transplantation and the center's desire to help potential transplant recipients.
The basic medical facts surrounding donation must be understood by all parties as
part of ethical decision making. Donor risk can be presented quantitatively using
US Renal Data System data as a baseline. Confirmation of accurate donor
understanding of risks, benefits, and alternatives is always a fundamental center
obligation. Donors should not be rejected except for the general reasons we
identify, and when these reasons do not seem to apply, the decision to deny
transplantation should be reconsidered.
PMID- 11007669
TI - Soluble Fas and soluble Fas-ligand in children with Escherichia coli O157:H7
associated hemolytic uremic syndrome.
AB - We measured soluble Fas-ligand (sFas-L) and soluble Fas (sFas) levels by sandwich
enzyme-linked immunosorbeny assay and compared them among (1) healthy controls (n
= 11), (2) children with hemorrhagic colitis (HC) caused by a non-verotoxin
producing pathogen (n = 23), (3) patients with uncomplicated Escherichia coli
O157:H7 HC (n = 14), and (4) children with O157:H7-associated hemolytic uremic
syndrome (HUS) (n = 24). Children with uncomplicated E coli O157:H7 HC and HUS
were matched for duration of enteric prodrome before blood sample collection. We
also compared sFas-L and sFas levels among patients with HUS according to
severity of renal dysfunction; abnormally increased sFas-L levels were noted in
only 4% of the children (n = 3). Abnormally high concentrations of sFas were
noted in 9% of the children with HC caused by a non-verotoxin-producing pathogen,
29% of the patients with uncomplicated E coli O157:H7 HC, and 69% of the children
with O157:H7-associated HUS. Compared with healthy controls, patients with HUS
had twofold greater concentrations of sFas (P: < 0.0001). Levels of sFas were not
statistically different between 14 patients with uncomplicated O157:H7 HC and 14
children with HUS (8.2 +/- 4.7 versus 11.0 +/- 4.6 U/mL, respectively; P: < 0.07)
when matched for time after onset of enteritis (7.0 +/- 3.7 versus 7.3 +/- 3.8
days, respectively). Greater concentrations of sFas were noted in patients with
HUS who developed oligoanuria (n = 10; P: < 0.007), required peritoneal dialysis
(n = 10; P: < 0.007), or had a decreased glomerular filtration rate (n = 5; P: <
0.002) 1 year later. Our data show that plasma concentrations of sFas but not
sFas-L are abnormally increased in children with O157:H7 infections. Levels of
sFas are associated with severity of renal dysfunction during HUS. Further
studies are needed to clearly determine the role and origin of circulating sFas
among children with infections caused by E coli O157:H7.
PMID- 11007670
TI - A novel interpretation of the role of von Willebrand factor in thrombotic
microangiopathies based on platelet adhesion studies at high shear rate flow.
AB - Clinical manifestations of thrombotic microangiopathies (TMA) are secondary to
platelet aggregation and thrombotic occlusion of the microvasculature of the
affected organs. Abnormalities in von Willebrand factor (vWF) in these patients
were considered instrumental in promoting the process leading to microvascular
thrombosis. We evaluated the capacity of plasma in these patients to induce
adhesion of normal platelets and thrombus formation under conditions of
controlled fluid shear stress. We also studied vWF multimeric distribution to
establish whether abnormalities of this glycoprotein correlate with platelet
adhesion and thrombus formation. Plasma from patients in the acute phase and
remission showed the same capacity to induce platelet adhesion and thrombus
formation at a low level of shear rate (600 sec(-1)) as plasma from control
subjects. At a high shear rate (1,500 sec(-1)), platelet adhesion and thrombus
dimensions were significantly increased (P: < 0.05) by plasma from patients with
TMA compared with controls. The capacity to enhance thrombus formation at high
shear stress was present during the acute phase and disease remission and did not
correlate with the presence of unusually large vWF multimers. Increased thrombus
formation with patient plasma is completely normalized by blocking the
interaction of vWF with the platelet receptors, glycoprotein (GP)Ib and GPIIb
IIIa, suggesting that the phenomenon is completely mediated by vWF. Our results
suggest the possibility of an intrinsically altered vWF molecule in these
patients that is probably more effective than normal vWF in mediating platelet
adhesion and thrombus formation.
PMID- 11007671
TI - Characterization of early IgA nephropathy.
AB - Histological grading of 45 patients with clinical early immunoglobulin A (IgA)
nephropathy was correlated with disease progression over a median follow-up of
123 months. Clinical early IgA nephropathy was defined as a serum creatinine
level of 1.3 mg/dL or less, proteinuria of 0.4 g/d or less of protein, and the
absence of hypertension at the time of renal biopsy. Disease progression was
related to the occurrence of impaired renal function, increased proteinuria, and
hypertension. We applied a previously described chronicity-based histological
grading to the renal biopsy specimen and also assessed acute glomerular lesions.
Disease progression was observed in 44.4% of these patients. Forty patients (89%)
showed glomerular grade 1 (GG1) and 5 patients (11%) showed GG2, but this grading
did not correlate with disease progression. However, when GG1 was subdivided into
GG1a (mean sclerosis per glomerulus <10%) and GG1b (mean sclerosis per glomerulus
10% to <25%), GG1a correlated with nonprogressive disease. Tubulointerstitial
grade also correlated with disease progression but was associated with a low
sensitivity for predicting nonprogressive disease. Hyaline arteriolosclerosis and
acute glomerular lesions did not correlate with disease progression. The
chronicity-based histological grading is not only applicable to clinical early
IgA nephropathy, but also more importantly, it characterizes GG1a in a subset of
patients with a very low risk for disease progression, which can be regarded as
genuine early IgA nephropathy.
PMID- 11007672
TI - ANCA-associated crescentic glomerulonephritis with mesangial IgA deposits.
AB - Antineutrophil cytoplasmic autoantibodies (ANCA) are commonly associated with a
necrotizing and crescentic glomerulonephritis (GN) that is pauci-immune, with few
or no glomerular immune complex deposits detectable by immunofluorescence (IF) or
electron microscopy (EM). Immunoglobulin A (IgA) nephropathy may also be manifest
as a crescentic GN, but it is characterized by mesangial immune complex deposits
containing IgA and is rarely associated with myeloperoxidase (MPO)- or proteinase
3 (PR3)-specific ANCA when an enzyme immunoassay is used to detect these
antibodies. This report describes six patients with severe crescentic GN with
mesangial IgA deposits by IF and mesangial electron-dense deposits by EM in
patients with positive ANCA serological test results (four patients, anti-PR3;
one patient, anti-MPO; one patient, anti-PR3 and anti-MPO). Patients presented
with acute or progressive renal insufficiency, hematuria, proteinuria (nephrotic
range in two patients), and hypertension. Three patients had evidence of systemic
vasculitis: two patients at initial presentation and one patient later in the
clinical course. Renal biopsy specimens showed crescents in greater than 50% of
glomeruli in all cases, but only mild, focal and segmental mesangial and
endocapillary hypercellularity, more typical of ANCA-associated crescentic GN
than of crescentic IgA nephropathy without associated ANCA. Semiquantitative
analysis of mesangial and endocapillary cellularity performed on renal biopsy
slides from these six patients and from eight ANCA-negative patients with IgA
nephropathy and crescents in greater than 50% of glomeruli showed significantly
greater hypercellularity in the ANCA-negative cases. Three of five ANCA-positive
patients for whom follow-up clinical data were available showed improved renal
function after treatment with cyclophosphamide and corticosteroids and have not
developed end-stage renal disease 17, 20, and 25 months postbiopsy. The remaining
two patients were dialysis dependent at the time of biopsy and have remained so
despite treatment with cyclophosphamide and corticosteroids. The findings suggest
an overlap syndrome of ANCA-associated crescentic GN and IgA nephropathy that
resembles the former both histologically and in its potential to respond to
aggressive therapy if detected relatively early in its course.
PMID- 11007673
TI - Effect of posture on sodium excretion and diuretic efficacy in nephrotic
patients.
AB - It is well known that posture affects natriuresis in cirrhosis and heart failure.
This study evaluates the role of posture on spontaneous urinary salt excretion
(U(Na)V) and diuretic-induced natriuresis in nephrotic patients with mild renal
impairment. U(Na)V and plasma concentrations of the main hormones involved in
sodium regulation were evaluated at baseline (Baseline) and after furosemide
administration (20 mg intravenously at 8:00 AM [Diuretic]) in seven nephrotic
patients with mild renal impairment (creatinine clearance, 68.5 +/- 7.6 mL/min)
in either the supine or upright position for 6 hours (from 8:00 AM to 2:00 PM).
At baseline, U(Na)V was greater in the supine than upright position (sodium, 51.8
+/- 6.2 versus 38.3 +/- 6.1 mEq/d; P: < 0.01). Similarly, furosemide was more
effective in increasing U(Na)V in the supine (sodium, 51.8 +/- 6.2 to 87.4 +/-
9.1 mEq/d; P: < 0.005) than upright position (sodium, 38.3 +/- 6.1 to 59.0 +/-
6.8 mEq/d; P: = not significant). Consequently, body weight decreased in the
supine but not the upright position (-0.73 +/- 0.15 versus -0.17 +/- 0.22 kg; P:
< 0. 05). Peripheral renin activity (PRA) and plasma aldosterone (Aldo)
concentrations were greater in the upright than supine position at both Baseline
and Diuretic. A similar pattern was observed for hematocrit, used as an index of
plasma volume. In addition, a positive correlation was detected between
hematocrit and PRA (r = 0.89; P: < 0.001) in the upright position. Postural
changes did not influence plasma concentrations of atrial natriuretic peptide.
These data indicate that in nephrotic patients with mild impairment of glomerular
filtration rate, the upright position causes a reduction in plasma volume; this
hypovolemia activates the renin-Aldo system responsible for sodium retention in
unstimulated conditions and a blunted natriuretic response to furosemide.
PMID- 11007674
TI - Increased prevalence of polycystic kidney disease type 2 among elderly polycystic
patients.
AB - Autosomal dominant polycystic kidney disease (ADPKD) is genetically
heterogeneous, with at least three chromosomal loci (PKD1, PKD2, and PKD3)
accounting for the disease. Mutations in the PKD2 gene, on the long arm of
chromosome 4, are estimated to be responsible for 15% of the cases of ADPKD,
based on linkage studies. PKD2 is a milder form of the disease, with a mean age
of end-stage renal disease (ESRD) approximately 20 years later than PKD1. The
object of this study is to determine the proportion of elderly patients with
ADPKD with ESRD who harbor mutations in the PKD2 gene. We analyzed all exons and
intron-exon boundaries of the PKD2 gene by single-strand conformation
polymorphism analysis and silver staining technique in 46 patients with ADPKD who
reached ESRD after the age of 63 years or were not yet undergoing renal
replacement therapy (RRT) by that age. We performed exactly the same studies in a
control group of 40 patients with ADPKD with unknown gene status aged younger
than 63 years. In 22 patients, a mutation in the PKD2 gene was defined: 18 of 46
patients from the elderly group and 4 of 40 patients from the control group. We
identified 14 different mutations: 4 nonsense mutations, 1 missense mutation, 5
small deletions, 2 insertions, 1 deletion of the whole PKD2 gene, and 1 splicing
mutation. Five of these mutations previously were described by our group. Three
of the mutations reported in the present study are recurrent. The prevalence of
PKD2 disease among elderly patients with ADPKD undergoing RRT is 39.1%, almost
three times the prevalence of the disease in the general ADPKD population.
PMID- 11007675
TI - Cytotoxicity of myeloma light chains in cultured human kidney proximal tubule
cells.
AB - We evaluated the effect of eight species of light chains on cultured human kidney
proximal tubule cell proliferation. Exposure to light chains for 48 hours caused
dose-dependent inhibition in tritium ((3)H)-thymidine incorporation by simian
virus 40 immortalized human proximal tubule cells, although the effect was
variable among different species of light chains. We studied cytotoxic effects of
selected toxic light chains in further detail. Two of these light chains caused
significant DNA degradation. A lambda-light chain caused lactate dehydrogenase
release from exposed cells at 48 hours, but not at 24 hours. Cytomorphological
and electron microscopic examination of cells exposed to light chains for 24
hours showed condensed nuclei, cell detachment, paucity of mitotic activity, and
apoptosis, and at 48 hours of exposure, changes consistent with necrosis.
Apoptosis assay by terminal deoxynucleotidyl transferase-mediated deoxyuridine
triphosphate nick-end labeling method showed a sixfold increase in the number of
apoptotic cells exposed to the same lambda-light chain for 24 hours. Rhodamine
phalloidin staining showed variable but significant disruptions in the actin
cytoskeleton. These studies show that some myeloma light chains are toxic to
cultured human proximal tubule cells and induce cytoskeletal injury and DNA
damage consistent with apoptosis followed by secondary necrosis. Direct proximal
tubule cell toxicity may be an important mechanism of renal involvement in
multiple myeloma.
PMID- 11007676
TI - Evidence that chronicity of hyponatremia contributes to the high urate clearance
observed in the syndrome of inappropriate antidiuretic hormone secretion.
AB - The high fractional excretion (FE) of uric acid observed in hyponatremia
associated with the syndrome of inappropriate secretion of antidiuretic hormone
(SIADH) is commonly attributed to the volume-expanded state, although volume
expansion in normonatremic volunteers is unable to increase urate clearance to a
degree similar to that in SIADH. The goal of the present study is to analyze
whether hyponatremia by itself could influence the FE of uric acid, as well as
the effects of intravascular volume and glomerular filtration rate on FE of uric
acid in SIADH. This study examines the effects of a 2-L infusion of isotonic
saline over 24 hours on FE of uric acid in 9 normonatremic volunteers and 17
hyponatremic patients with SIADH. We also studied the FE of uric acid in 6
patients with SIADH with only mild water retention and the urate and creatinine
clearances in 18 hyponatremic patients with SIADH before and after normalization
of serum sodium levels by water restriction. When infusing 2 L of isotonic saline
over 24 hours in healthy subjects, there was a decrease in plasma protein
concentration of 8%, suggesting a similar degree of volume expansion than in
patients with SIADH. The FE of uric acid did not increase to the same extent (9%
+/- 1.5% versus 17% +/- 1.5%; P: < 0.01). Conversely, in 6 hyponatremic patients
with mild water retention (1 L), the FE of uric acid was still high despite
indirect signs of only a small increase in plasma volume. The mainstay of these
observations is that chronicity of hyponatremia by itself could affect urate
excretion. We also observed that in the patients with SIADH, high FE of uric acid
inversely correlated with glomerular filtration rate (r = -0.66; P: < 0.01) only
during the hyponatremic state. These data suggest that hyponatremia by itself,
combined with mild volume expansion and glomerular filtration rate, has a role in
the high FE of uric acid in the SIADH.
PMID- 11007677
TI - Revascularization of renal artery stenosis in patients with renal insufficiency.
AB - The incidence and prevalence of end-stage renal disease (ESRD), particularly in
the elderly population, have continued to increase in the United States. It is
estimated that 10% to 20% of the elderly patients with ESRD have potentially
remediable renal vascular disease. The purpose of the present study is to examine
the results of renal artery revascularization in 20 patients aged older than 55
years with chronic renal failure (serum creatinine level >2 mg/dL) with proximal
renal artery stenosis (RAS) diagnosed by magnetic resonance angiography (MRA) who
underwent surgical or percutaneous revascularization. Patients were followed up
closely in the postrevascularization period; renal function was monitored and
potential complications of the procedure were carefully noted. Four of the 20
patients developed serious complications, including 3 patients with clinically
significant atheroembolic disease and 1 patient with renal artery dissection.
Seven patients developed greater than 5% eosinophilia. Five of the 20 patients
had a deterioration in renal function 3 to 6 months after the procedure, and only
5 patients had a reduction in serum creatinine concentration 3 to 6 months after
the procedure. The present study suggests that in elderly patients with chronic
renal failure and proximal RAS, revascularization of renal vessels is associated
with a high complication rate, and improvement in renal function occurs in only
25% of the patients. Whether revascularization can slow the rate of progression
of renal failure remains uncertain and can only be answered by a large
prospective trial.
PMID- 11007678
TI - Renal cell carcinoma in acquired cystic kidney disease: volume growth rate
determined by helical computed tomography.
AB - The aim of this study is to determine the growth rate and behavior of renal cell
carcinoma in chronic hemodialysis patients with acquired cystic kidney disease
(ACKD). Renal cell carcinomas in 17 hemodialysis patients (mean age, 52 +/- 11
years; mean hemodialysis duration, 7.2 +/- 3.3 years) with ACKD were examined
with helical computed tomography (CT) for 0.5 to 6.0 years (mean, 2.1 +/- 1.9
years). The 17 renal cell carcinomas were histologically proven and graded after
nephrectomy (16 patients) or autopsy (1 patient). Tumor volume was estimated by
counting the number of pixels in the tumor and a 1-cm(2) area on helical computed
tomographic scan using a personal computer. Estimated volume growth rates and
doubling times of the carcinoma were correlated with histological grades. Fifteen
of the 17 neoplasms (88%) were less than 3 cm in diameter at initial CT. The
overall volume growth rate was 0.07 to 17.34 cm(3)/y (mean, 4.14 +/- 5.66
cm(3)/y), and the estimated volume-doubling time was 0. 08 to 23.31 years (mean,
5.09 +/- 6.99 years). The mean growth rate of the 3 grade 3 carcinomas was 6.01
+/- 4.50 cm(3)/y (range, 0.88 to 9.28 cm(3)/y), which was significantly greater
than that of the 9 grade 1 carcinomas (0.40 +/- 0.40 cm(3)/y; range, 0.09 to 1.37
cm(3)/y) or the 5 grade 2 tumors (0.79 +/- 0.74 cm(3)/y; range, 0.12 to 2.00
cm(3)/y). Eleven of the 17 carcinomas (65%) had more than a 1-year volume
doubling time. The 3 grade 3 neoplasms and 1 of the grade 2 lesions had less than
a 0.5-year doubling time.
PMID- 11007679
TI - Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal
Failure Study Group.
AB - Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the
cardiac atria, has been shown to improve renal function in multiple animal models
of acute renal failure. In a recent multicenter clinical trial of 504 patients
with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need
for dialysis only in the oliguric patients. In the present study, 222 patients
with oliguric acute renal failure were enrolled into a multicenter, randomized,
double-blind, placebo-controlled trial designed to assess prospectively the
safety and efficacy of ANP compared with placebo. Subjects were randomized to
treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min;
synthetic form of human ANP) or placebo. Dialysis and mortality status were
followed up for 60 days. The primary efficacy end point was dialysis-free
survival through day 21. Dialysis-free survival rates were 21% in the ANP group
and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of
the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and
9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed
dialysis but did not receive it. Although a trend was present, there was no
statistically significant beneficial effect of ANP in dialysis-free survival or
reduction in dialysis in these subjects with oliguric acute renal failure.
Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups,
respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%)
patients in the ANP and placebo groups had systolic blood pressures less than 90
mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease
in systolic blood pressure was significantly greater in the anaritide group than
placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized
population with oliguric acute renal failure had an overall high morbidity and
mortality.
PMID- 11007680
TI - Intravenous iron dextran treatment in predialysis patients with chronic renal
failure.
AB - Iron deficiency anemia is common in patients with chronic renal failure not
undergoing hemodialysis. Current therapy consists of oral or intravenous (IV)
iron dextran (IVID). The standard IV regimen is 100 to 200 mg/dose for a 1-g
total dose. We hypothesized that 500 mg/wk of IVID for two doses would be less
costly and equally effective as 200 mg/wk for five doses. We prospectively
studied 22 patients with creatinine clearances less than 50 mL/min who were not
undergoing dialysis and had anemia and evidence of iron deficiency (ferritin
level <100 ng/mL or transferrin saturation [TSAT] <20%). Patients were randomized
into two groups: group I (n = 8), 200 mg/wk of IVID for 5 weeks, and group II (n
= 14), 500 mg/wk of IVID for 2 weeks. All patients tolerated IVID infusions
without serious adverse reactions. Over the 6-month follow-up, both groups
experienced an increase in hemoglobin levels from baseline. Ferritin levels in
both groups increased (P < 0.005), peaked at 2 weeks, then declined thereafter.
Over the 6-month follow-up, both groups experienced significant improvement,
although the beneficial effects of group II declined at a significantly faster
rate than group I (P = 0.003). There was no significant difference in change in
ferritin levels between groups. TSAT peaked at 2 weeks in both groups (P < 0.
001). Group I experienced a significant increase in TSAT throughout the 6-month
follow-up (P < 0.03), and group II achieved a significant increase in TSAT at 2
weeks, but not at 3 and 6 months. There was no significant difference in
pretreatment to posttreatment change in TSAT. Treatment in group II was 35.2%
more cost-effective than in group I ($965 versus $1,490, respectively). We
conclude that IVID, 500 mg/wk, for 2 weeks is as effective and safe as 200 mg/wk
for 5 weeks, but much less costly.
PMID- 11007681
TI - Prevalence of sleep disturbances in chinese patients with end-stage renal failure
on continuous ambulatory peritoneal dialysis.
AB - Patients with end-stage renal failure (ESRF) are reported to have a high
prevalence of sleep disorders, such as daytime sleepiness, insomnia, restless
legs syndrome (RLS), and obstructive sleep apnea syndrome (OSAS). However, there
are few published data from Southeast Asia. A sleep questionnaire was
administered to 201 patients (103 men) at the continuous ambulatory peritoneal
dialysis (CAPD) outpatient clinic to assess sleep problems. Patients had a mean
age of 56.7 +/- 12 (SD) years, with a mean body mass index (BMI) of 23.6 +/- 3.5
kg/m(2). Daytime sleepiness was the most frequent symptom (77.1%), and frequent
awakening occurred in 69% of the patients. Sleep-onset insomnia and sleep
maintenance insomnia occurred in 73% and 60% of the patients, respectively. Sixty
two percent of the patients reported symptoms of RLS, which significantly
correlated with sleep-onset insomnia (odds ratio [OR], 2.9; 95% confidence
interval [CI], 1.5 to 5.5; P = 0.001) and sleep-maintenance insomnia (OR, 2.1;
95% CI, 1.2 to 3.8; P = 0.014). The prevalence of OSAS was estimated by the
frequency of the following symptoms: extremely loud snoring, 7 patients (3.5%);
observed choking, 21 patients (10.5%); witnessed apnea, 11 patients (5.6%);
snoring and witnessed apnea, 6 patients (3%); disruptive snoring, 29 patients
(14.4%); and disruptive snoring and witnessed apnea, 3 patients (1.5%). This
questionnaire survey confirmed a high prevalence of daytime sleepiness, insomnia,
and RLS in patients with ESRF undergoing CAPD but showed a relatively low
prevalence of OSAS of up to 14.4%, which may be related to the low BMI of these
patients with ESRF compared with other populations. Whether this contributes to
the overall better survival observed in some Asian patients with ESRF undergoing
dialysis needs further investigation.
PMID- 11007682
TI - Effect of the vitamin D analogues paricalcitol and calcitriol on bone mineral in
vitro.
AB - Paricalcitol (19-nor-1,25-dihydroxyvitamin D(2)), a new vitamin D analogue,
recently became available for the treatment of hyperparathyroidism in patients
with end-stage renal disease. It is safe and effective in suppressing parathyroid
hormone, with apparently less propensity for hypercalcemia than calcitriol (1, 25
dihydroxyvitamin D(3)). However, the mechanism of action on bone has not been
fully elucidated. This study compares the effects of paricalcitol and calcitriol
on the bone mineral. Neonatal (5- to 7-day-old) mouse calvariae were incubated in
the absence or presence of either paricalcitol or calcitriol for 48 hours, and
calcium flux, osteocalcin and acid and alkaline phosphatase activity, and
interleukin-6 (IL-6) release were determined. Increasing concentrations of both
calcitriol and paricalcitol increased calcium efflux. At lower concentrations,
paricalcitol had no effect on acid phosphatase activity; however, at 10(-8)
mol/L, paricalcitol caused a significant increase similar to that of calcitriol
at 10(-9) mol/L. Increasing concentrations of paricalcitol had no effect on
alkaline phosphatase activity, whereas calcitriol (10(-8) mol/L) caused
significant inhibition. At low concentrations, paricalcitol had no effect on
osteocalcin release; however, at 10(-8) mol/L, both compounds significantly
increased osteocalcin production. Neither compound had an effect on IL-6 release.
These data show that: (1) at low concentrations, both compounds induce a similar
calcium efflux from cultured bone; (2) at low concentrations, paricalcitol has no
effect on osteocalcin or acid and alkaline phosphatase activity; (3) at greater
concentrations, paricalcitol and calcitriol have similar effects on acid
phosphatase and osteocalcin activity; (4) calcitriol, but not paricalcitol,
inhibits alkaline phosphatase release; and (5) the bone-resorbing effect of both
compounds is independent of IL-6 release. Thus, although both compounds have
similar effects on calcium efflux from bone, at therapeutic concentrations,
paricalcitol does not seem to inhibit osteoblast activity. This may explain, in
part, the lower calcemic effect of paricalcitol.
PMID- 11007683
TI - Assessment of sonographic venous peak systolic velocity in detecting hemodialysis
arteriovenous graft stenosis.
AB - There is no single effective means of assessing arteriovenous access function,
although monitoring hemodialysis venous pressure (VP) or measuring access
recirculation may be of some benefit. The present study assesses prospectively
the efficacy of following the peak systolic velocity (PSV) as a single measure to
detect arteriovenous graft (AVG) stenosis. PSV was measured in 12 patients after
new AVG placement and at approximately 2-month intervals. Angiography was also
performed after new graft placement and when PSV was elevated to greater than 200
cm/sec, hemodialysis access VP increased to greater than 150 mm Hg on three
consecutive readings, or access recirculation increased to greater than 11%. PSV
was then compared with results from angiography, VP monitoring, and access
recirculation. The 12 patients underwent 34 PSV studies, followed by angiography
on 25 occasions. Each patient underwent at least one angiogram. Each abnormal PSV
value was confirmed with the finding of stenosis on angiogram, except for two
patients with PSVs greater than 400 cm/sec and normal angiography results. VP and
recirculation were not elevated. During this period, two patients developed
thrombosis of the AVG, and two patients underwent angioplasty with improvement in
PSV. We conclude that elevations in PSV measured at the venous anastomosis are an
effective means of screening for AVG stenosis, AVG stenosis can occur early after
AVG placement, and elevated VP and recirculation are late findings in AVG
dysfunction.
PMID- 11007684
TI - Salvage of occluded autologous arteriovenous fistulae.
AB - Well-functioning vascular access is essential to optimizing outcomes in
hemodialysis patients. Initial placement of greater numbers of autologous
arteriovenous fistulae (AVFs) is needed, as is more attention to salvage of such
accesses when they become occluded. In this study, thrombolysis with small doses
of thrombolytic agents in combination with balloon angioplasty was attempted in
15 patients with 16 autologous AVFs (7 forearm AVFs, 8 upper-arm AVFs). Either
urokinase (UK; mean dose, 109,375 U) or tissue plasminogen activator (tPA; mean
dose, 7.1 mg) was used for thrombolysis. The technical success rate was 94%,
whereas long-term patency was achieved in 81% of the accesses. Failure to achieve
long-term patency was caused by the inability to achieve adequate drainage in 2
patients. In 1 patient, technical inability to cannulate the access and penetrate
the venous end of a basilic vein transposed fistula occurred. One patient was
successfully declotted and angioplastied twice. Successful salvage of thrombosed
AVFs can be safely performed with much lower doses of thrombolytic agents than
previously reported. In addition, tPA is effective in this setting, in addition
to UK. Salvage of occluded autologous AVFs should be attempted more frequently
than is currently practiced and would result in improved hemodialysis patient
outcomes.
PMID- 11007685
TI - Anthropometric measures and risk of death in children with end-stage renal
disease.
AB - We evaluated the association between anthropometric measurements and death among
pediatric patients with end-stage renal disease (ESRD) using data from the
Pediatric Growth and Development Special Study (PGDSS) from the US Renal Data
System. Height, growth velocity, and body mass index (BMI) were used for the
analysis of 1,949 patients in the PGDSS. To standardize these measurements, SD
scores (SDSs) were calculated using population data from the Third National
Health and Nutrition Examination Survey. Using Cox proportional hazards models,
we assessed the association between anthropometric measures and death,
controlling for demographic factors and stratifying by age. Multivariate analysis
showed that each decrease by 1 SDS in height was associated with a 14% increase
in risk for death (adjusted relative risk [aRR], 1.14; 95% confidence interval
[CI], 1.02 to 1.27; P = 0.017). For each 1 SDS decrease in growth velocity among
patients in our sample, the risk for death increased by 12% (aRR, 1.12; 95% CI,
1.00 to 1.25; P = 0.043). There was a statistically significant U-shaped
association between BMI and death (P = 0.001), with relatively low and high BMIs
associated with an increased risk for death. In children with ESRD, growth delay
and extremes in BMI are associated with an increased risk for mortality.
PMID- 11007686
TI - Long-term prognosis and incidence of acute myocardial infarction in patients on
chronic hemodialysis. The Okinawa Dialysis Study Group.
AB - Mortality from cardiovascular disease is high in chronic dialysis patients. We
observed the occurrence of acute myocardial infarction (AMI) in the chronic
dialysis population in Okinawa, Japan. A total of 3,741 chronic dialysis patients
(2,073 men, 1,668 women) were followed up for 10 years from April 1, 1988, to
March 31, 1998. Only definite cases of AMI were registered. Data were compared
with AMI registry data obtained from the general population of the same district.
The total duration of observation was 15,748.8 patient-years. During the study
period, 61 patients (40 men, 21 women) had AMI. The incidence of AMI was
3.9/1,000 patient-years (men, 4.4/1,000 patient-years; women, 3.1/1,000 patient
years). Twenty-four percent of the AMI cases occurred at 12 months after starting
dialysis therapy. Mean age at onset of AMI was 60.9 +/- 11. 4 (SD) years; 58.9 +/
11.4 years in men and 64.7 +/- 10.7 years in women. Survival rates after AMI
were 50.8% at 1 month, 45.0% at 6 months, 36.5% at 12 months, and 13.0% at 44
months. Patients with diabetes mellitus (DM) had a greater incidence of AMI and a
worse prognosis than patients without DM. The long-term prognosis of AMI was poor
in chronic dialysis patients.
PMID- 11007687
TI - Effect of apolipoprotein E polymorphism on serum lipid, lipoproteins, and
atherosclerosis in hemodialysis patients.
AB - Atherosclerosis and cardiovascular disease are the main causes of death in
hemodialysis patients. Possession of the apolipoprotein E4 (ApoE4) allele has
been associated with increased levels of serum lipids and with coronary and
carotid artery atherosclerosis. We investigated the possible relationship between
ApoE polymorphism and atherosclerosis risk factors in hemodialysis patients. Two
hundred sixty-nine hemodialysis patients (115 women, 154 men) were included in
our study. The mean patient age and mean hemodialysis duration were 45.8 +/- 15.3
years and 52.6 +/- 40.6 months, respectively. Testing was done on all patients to
determine ApoE genotype and serum levels of total cholesterol (T-Cho), low
density lipoprotein (LDL-C), high-density cholesterol (HDL-C), triglyceride (TG),
lipoprotein (a) (Lp[a]), intact parathormone (iPTH), and fibrinogen. ApoE
genotype was identified with the polymerase chain reaction. Ultrasonographic
measurement of carotid artery intima media thickness (IMT) was used to diagnose
atherosclerosis. We also analyzed ApoE polymorphism and risk factors such as age,
gender, duration of hemodialysis, smoking, and hypertension in relation to the
presence of atherosclerosis. Serum T-Cho and LDL-C levels were higher in patients
with the ApoE4/3 phenotype than in those with ApoE3/3 and ApoE3/2 phenotypes (P <
0.05). However, there was no statistically significant link between ApoE
polymorphism and serum levels of TG, HDL-C, or Lp(a) (P > 0.05). Apart from a
relationship with age and duration of hemodialysis (P < 0.05), we found no
significant association between atherosclerosis and ApoE polymorphism or the
other risk factors analyzed (P > 0.05). In conclusion, although ApoE polymorphism
significantly affects serum levels of T-Cho and LDL-C in hemodialysis patients,
this study indicates that ApoE polymorphism is not associated with the presence
of atherosclerosis in these individuals. The high incidence of atherosclerosis in
these patients underlines the need for further research on other possible
causative factors.
PMID- 11007688
TI - Renal arterial intervention and angiotensin blockade in atherosclerotic
nephropathy.
AB - Atherosclerotic renal arterial disease (ARAD) is becoming a more important cause
of end-stage renal failure. Diagnosis is more easily achieved because of greater
clinical suspicion and more refined screening tools. However, the medical and
interventional management of patients with ARAD is not well defined in the
literature because there have been few randomized trials. Because the use of
angiotensin-converting enzymes (ACE) inhibitors, and more recently angiotensin
antagonists, has become much more widespread, it is inevitable that we should,
knowingly or not, give these drugs to patients with ARAD. We describe 2 case
studies in which the angiotensin-antagonist irbesartan was given to 2 patients
with effectively single-functional kidneys after successful renal arterial
radiologic intervention. The rationale for the use of irbesartan was to control
BP, which had not responded to the initial arterial intervention, and took place
in patients both refractory to, and intolerant of, many other anti-hypertensive
drugs. Irbesartan successfully and safely reduced systemic BP, measured by use of
ambulatory BP, without prejudicing renal function (measured by use of individual
kidney function GFR).
PMID- 11007689
TI - Cyclosporine and tacrolimus-associated thrombotic microangiopathy.
AB - The development of thrombotic microangiopathy (TMA) associated with the use of
cyclosporine has been well documented. Treatments have included discontinuation
or reduction of cyclosporine dose with or without concurrent plasma exchange,
plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion.
However, for recipients of organ transplantation, removing the inciting agent is
not without the attendant risk of precipitating acute rejection and graft loss.
The last decade has seen the emergence of tacrolimus as a potent
immunosuppressive agent with mechanisms of action virtually identical to those of
cyclosporine. As a result, switching to tacrolimus has been reported to be a
viable therapeutic option in the setting of cyclosporine-induced TMA. With the
more widespread application of tacrolimus in organ transplantation, tacrolimus
associated TMA has also been recognized. However, literature regarding the
incidence of the recurrence of TMA in patients exposed sequentially to
cyclosporine and tacrolimus is limited. We report a case of a living donor renal
transplant recipient who developed cyclosporine-induced TMA that responded to the
withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen
plasma replacement therapy. Introduction of tacrolimus as an alternative
immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss
of the renal allograft. Patients who are switched from cyclosporine to tacrolimus
or vice versa should be closely monitored for the signs and symptoms of recurrent
TMA.
PMID- 11007690
TI - Endocapillary proliferative glomerulonephritis in a patient with parvovirus B19
infection.
AB - A 45-year-old woman developed acute nephritic syndrome after erythema
infectiosum. Laboratory data on admission showed decreased serum C3, C4, and CH50
levels and the presence of both immunoglobulin (Ig) M and IgG antibodies to human
parvovirus B19 (HPV). A renal biopsy showed diffuse endocapillary proliferative
glomerulonephritis. Immunofluorescence microscopy indicated 2+ granular staining
for IgG, IgM, and C3 over the mesangial area and along glomerular capillary
walls. HPV antigen was also detected in glomeruli by immunohistochemistry.
Electron microscopy showed electron-dense deposits in the subendothelial space
and the paramesangial area. These findings suggest that immune complex-type
glomerulonephritis is caused by glomerular deposition of HPV antigen-antibody
complexes in some patients with HPV infection.
PMID- 11007691
TI - Choroidal calcifications in patients with Gitelman's syndrome.
AB - Gitelman's syndrome is a renal tubular disorder characterized by a sodium and
chloride reabsorption defect in distal tubular cells that determines hypokalemia,
metabolic alkalosis, hypomagnesemia, and low calcium excretion. The presence of
choroidal calcifications was sought in five patients with Gitelman's syndrome by
ophthalmic examination, fluorescein angiography, indocyanine green angiography,
and ocular ultrasonography. Calcifications observed in the choroid of two
patients were shown by ultrasonography in both patients. Ophthalmic and
fluorangiographic examinations detected this alteration in one of the two
subjects. Chondrocalcinosis was found in one patient with choroidal
calcifications. These findings suggest that precipitation of calcium salts can
occur in the choroidal tissue of patients with Gitelman's syndrome. Deposits
appeared to be well seen by ultrasonography because of their depth in ocular
tissues. Sclerochoroidal calcifications may be favored by the low calcium
excretion, which is associated with normal intestinal calcium absorption in
patients with Gitelman's syndrome.
PMID- 11007692
TI - Mediators, markers, and modulators in the hemolytic uremic syndrome.
PMID- 11007693
TI - Toward more rational management of ischemic nephropathy: the need for clinical
evidence.
PMID- 11007694
TI - Understanding how aldosterone increases sodium transport.
PMID- 11007695
TI - A 14-year-old boy with kidney allograft failure in the first month after
transplantation.
PMID- 11007696
TI - Ace inhibitors and erythropoietin response in hemodialysis patients.
PMID- 11007697
TI - Indinavir nephropathy
PMID- 11007698
TI - Continuing medical education exercise, october 2000
PMID- 11007699
TI - Pauci-immune ANCA-positive crescentic glomerulonephritis associated with
metastatic adenocarcinoma of the lung.
AB - A 66-year-old woman developed rapidly progressive renal failure several days
after she was diagnosed with non-small cell carcinoma of the lung. Antineutrophil
cytoplasmic antibody test performed as an indirect immunofluorescence assay was
positive with a perinuclear pattern of staining (pANCA). The patient did not
improve with hemodialysis treatment and died on the second day after admission to
the hospital. A complete autopsy was performed and showed metastatic
adenocarcinoma of the lung and pauci-immune crescentic glomerulonephritis. A
literature search showed only 7 previously reported cases of malignant tumors
associated with ANCA-positive pauci-immune crescentic glomerulonephritis. The
clinicopathologic findings of the current and all previously reported cases and
possible relationship between ANCA-positive glomerulonephritis and malignancy are
discussed.
PMID- 11007700
TI - Familial interstitial nephritis with progressive renal failure.
AB - We describe a 53-year-old woman with chronic interstitial nephritis and
asymptomatic impairment of renal function. Seven members of her family were
suffering from renal failure and underwent hemodialysis. At the time of their
hospital admissions, they had shown evidence of end-stage renal failure at 40 to
50 years of age. Lack of proteinuria, hematuria, hypertension, hyperuricemia,
hearing loss, and visual impairment were present before the deterioration of the
renal function. Renal biopsy of the presented case indicated chronic interstitial
nephritis without glomerular basement membrane abnormalities. Progressive decline
of renal function and the inheritance pattern of autosomal dominance in this
family suggested the diagnosis of familial interstitial nephritis.
PMID- 11007701
TI - Parathyroid carcinoma in a dialysis patient.
AB - A 75-year-old woman who had been receiving dialysis for 3 years and had a long
history of chronic renal failure attributable to reflux nephropathy was
investigated for progressive hypercalcemia in the context of very high intact
parathormone (iPTH) levels. Imaging showed two functional parathyroid glands in
the neck. At parathyroidectomy, four variously enlarged parathyroid glands were
found and completely resected, without autotransplantation. The histology of one
of the glands showed invasive parathyroid carcinoma. Parathyroid carcinoma is a
very rare condition, with only 16 previous cases involving dialysis patients
described in the literature. We review the literature to draw together
presentational and therapeutic information on the management of this problem in
the setting of renal replacement therapy.
PMID- 11007702
TI - Granulomatous tubulointerstitial nephritis in the renal allograft.
AB - Granulomatous tubulointerstitial nephritis has rarely been described in renal
allografts. Of 1,574 renal allograft tissue specimens obtained from 514 patients
in the period 1993 to 1998, we report three cases (0.6%) with interstitial
nephritis containing multiple noncaseating granulomas. Biopsy specimen 1 was
obtained from a 44-year-old woman with a 6-day history of systemic Candida
albicans infection and showed multiple granulomas containing budding yeasts.
Biopsy specimen 2 was from a 33-year-old man who presented with miliary spread of
Mycobacterium tuberculosis 12 days before the allograft biopsy. Biopsy specimen 3
was from a 23-year-old woman who presented with Escherichia coli urinary
infection and bacteremia that was treated with antibiotics for 10 days before the
biopsy. Granulomatous inflammation in reponse to infectious agents or drugs in
immunosuppressed kidney transplant recipients can rarely give rise to allograft
interstitial nephritis that is distinct from acute rejection. To our knowledge,
there are no prior reports of granulomatous tubulointerstitial nephritis
associated with C albicans and E coli infection or antibiotic therapy in human
renal allografts.
PMID- 11007703
TI - In pursuit of novel therapies based on an understanding of renal growth
PMID- 11007704
TI - Adolescent depression: window of (missed?) opportunity.
PMID- 11007705
TI - Genetic epidemiology of major depression: review and meta-analysis.
AB - OBJECTIVE: The authors conducted a meta-analysis of relevant data from primary
studies of the genetic epidemiology of major depression. METHOD: The authors
searched MEDLINE and the reference lists of previous review articles to identify
relevant primary studies. On the basis of a review of family, adoption, and twin
studies that met specific inclusion criteria, the authors derived quantitative
summary statistics. RESULTS: Five family studies met the inclusion criteria. The
odds ratios for proband (subjects with major depression or comparison subjects)
versus first-degree relative status (affected or unaffected with major
depression) were homogeneous across the five studies (Mantel-Haenszel odds
ratio=2.84, 95% CI=2.31-3.49). No adoption study met the inclusion criteria, but
the results of two of the three reports were consistent with genetic influences
on liability to major depression. Five twin studies met the inclusion criteria,
and their statistical summation suggested that familial aggregation was due to
additive genetic effects (point estimate of heritability of liability=37%, 95%
CI=31%-42%), with a minimal contribution of environmental effects common to
siblings (point estimate=0%, 95% CI=0%-5%), and substantial individual-specific
environmental effects/measurement error (point estimate=63%, 95% CI=58%-67%). The
literature suggests that recurrence best predicts the familial aggregation of
major depression. CONCLUSIONS: Major depression is a familial disorder, and its
familiality mostly or entirely results from genetic influences. Environmental
influences specific to an individual are also etiologically significant. Major
depression is a complex disorder that does not result from either genetic or
environmental influences alone but rather from both. These findings are notably
consistent across samples and methods and are likely to be generally applicable.
PMID- 11007706
TI - Cost-effectiveness of services for mentally ill homeless people: the application
of research to policy and practice.
AB - OBJECTIVE: About one-quarter of homeless Americans have serious mental illnesses.
This review synthesizes research findings on the cost-effectiveness of services
for this population and their relevance for policy and practice. METHOD: Service
interventions for seriously mentally ill homeless people were grouped into three
overlapping categories: 1) outreach, 2) case management, and 3) housing placement
and transition to mainstream services. Data were reviewed both from experimental
studies with high internal validity and from observational studies, which better
reflect typical community practice. RESULTS: In most studies, specialized
interventions are associated with significantly improved outcomes, most
consistently in the housing domain, but also in mental health status and quality
of life. These programs are also associated with increased use of many types of
health service and housing assistance, resulting in increased costs in most
cases. The value of these programs to the public thus depends on whether their
greater effectiveness is deemed to be worth their additional cost. CONCLUSIONS:
Innovative programs for seriously mentally ill homeless people are effective and
are also likely to increase costs in many cases. Their value ultimately depends
on the moral and political value society places on caring for its least-well-off
members.
PMID- 11007707
TI - Neural networks: neural systems III.
PMID- 11007708
TI - Respect from our medical colleagues: how much is too much?
PMID- 11007709
TI - Naltrexone treatment for a 3-year-old boy with self-injurious behavior.
PMID- 11007710
TI - William James, 1842-1910.
PMID- 11007711
TI - Natural course of adolescent major depressive disorder in a community sample:
predictors of recurrence in young adults.
AB - OBJECTIVE: The primary purpose was to identify factors related to the recurrence
of major depressive disorder during young adulthood (19-23 years of age) in a
community sample of formerly depressed adolescents. METHOD: A total of 274
participants with adolescent-onset major depressive disorder were assessed twice
during adolescence and again after their 24th birthday. Lifetime psychiatric
information was obtained from their first-degree relatives. Adolescent predictor
variables included demographic characteristics, psychosocial variables,
characteristics of adolescent major depressive disorder, comorbidity, family
history of major depressive disorder and nonmood disorder, and antisocial and
borderline personality disorder symptoms. RESULTS: Low levels of excessive
emotional reliance, a single episode of major depressive disorder in adolescence,
low proportion of family members with recurrent major depressive disorder, low
levels of antisocial and borderline personality disorder symptoms, and a positive
attributional style (males only) independently predicted which formerly depressed
adolescents would remain free of future psychopathology. Female gender, multiple
major depressive disorder episodes in adolescence, higher proportion of family
members with recurrent major depressive disorder, elevated borderline personality
disorder symptoms, and conflict with parents (females only) independently
predicted recurrent major depressive disorder. Comorbid anxiety and substance use
disorders in adolescence and elevated antisocial personality disorder symptoms
independently distinguished adolescents who developed recurrent major depressive
disorder comorbid with nonmood disorder from those who developed pure major
depressive disorder. CONCLUSIONS: Formerly depressed adolescents with the risk
factors identified in this study are at elevated risk for recurrence of major
depressive disorder during young adulthood and therefore warrant continued
monitoring and preventive or prophylactic treatment.
PMID- 11007712
TI - Identifying risk factors and key strategies in linkage to outpatient psychiatric
care.
AB - OBJECTIVE: The substantial failure of psychiatric patients to engage in
outpatient specialty mental health care after an acute hospitalization at a time
when managed care companies and others increasingly hold hospitals accountable
for outcomes underscores the importance of identifying patients at high risk for
not completing referrals. This study explored patient risk factors for not
completing referrals and examined the success of several interventions targeted
to achieving linkage with outpatient care. METHOD: A clinically detailed,
structured form was used in abstracting information from the medical records of
229 inpatients with a primary psychiatric diagnosis. Clinicians and staff at
outpatient programs were contacted to determine whether patients completed their
referrals. RESULTS: Approximately two-thirds (65%) of the patients failed to
attend scheduled or rescheduled initial outpatient mental health appointments
after a hospital discharge. At high risk for unsuccessful linkage to outpatient
care were patients with a persistent mental illness and those who had no prior
public psychiatric hospitalization, were admitted involuntarily, and had longer
lengths of stay. Controlling for risk factors, three clinical interventions used
during the hospital stay more than tripled the odds of successful linkage to
outpatient care: communication about patients' discharge plans between inpatient
staff and outpatient clinicians, patients' starting outpatient programs before
discharge, and family involvement during the hospital stay. CONCLUSIONS:
Effective clinical bridging strategies can be used to avoid unnecessary gaps in
the delivery of psychiatric services. Incorporating these strategies into routine
care would enhance continuity of care, especially for some high-risk patients.
PMID- 11007713
TI - Methods to improve diagnostic accuracy in a community mental health setting.
AB - OBJECTIVE: This study determined the extent to which adding structured procedures
improved diagnostic accuracy for outpatients with severe mental illness in a
community mental health setting. METHOD: The Structured Clinical Interview for
DSM-III-R (SCID) was used to interview 200 psychiatric outpatients. A research
nurse reviewed medical records and amended the SCID diagnoses accordingly. A
research psychiatrist or psychologist reviewed the diagnostic data and
interviewed each patient to verify or further modify the previous findings.
Diagnostic outcomes at each step of the procedure were compared to determine
whether adding additional data improved diagnostic accuracy. The additional time
required for each element of the diagnostic procedure was also assessed. RESULTS:
Kappa comparisons of the different diagnostic levels showed that adding
additional data significantly improved accuracy. Diagnoses rendered by combining
the SCID and review of the medical record were the most accurate, followed by the
SCID alone, and then diagnoses made by psychiatrists during routine care. In
addition, the SCID alone identified five times as many current and past secondary
diagnoses as were documented routinely in patients' charts. CONCLUSIONS:
Combining structured interviewing with a review of the medical record appears to
produce more accurate primary diagnoses and to identify more secondary diagnoses
than routine clinical methods. The patients' knowledge of their diagnoses was
limited, suggesting a need for patient education in this setting. Whether use of
structured interviewing in routine practice improves patient outcomes deserves
further study.
PMID- 11007714
TI - Disability and quality of life in social phobia: epidemiologic findings.
AB - OBJECTIVE: Social phobia in clinical studies is vividly associated with extensive
disability and reduced quality of life. It is difficult to obtain a clear
portrayal of the impairment associated with social phobia in community samples.
Furthermore, it has been unclear in prior studies to what extent indices were
attributable to social phobia as opposed to comorbid major depression. The
authors examined relevant data from the Ontario Health Survey Mental Health
Supplement. METHOD: The Ontario Health Survey Mental Health Supplement, a survey
of more than 8,000 residents of Ontario, Canada, aged 15-64, used the University
of Michigan Composite International Diagnostic Interview to assign DSM-III-R
diagnoses. Several indicators of disability and quality of life were included.
The authors compared these indices for persons with and without social phobia and
adjusted where indicated for the effects of major depression and relevant
sociodemographic factors. RESULTS: Persons with social phobia were impaired on a
broad spectrum of measures, ranging from dropping out of school to experiencing
disability in one's main activity. They were also significantly more likely than
persons without social phobia to rate themselves as "low functioning" on the
Quality of Well-Being Scale and to report dissatisfaction with many aspects of
life. Depressive comorbidity seemed to contribute only modestly to these
outcomes. CONCLUSIONS: Social phobia can be a serious, disabling anxiety disorder
associated with marked reduction in quality of life. Impairment in social phobia
is substantial, even in the absence of comorbid major depression.
PMID- 11007715
TI - Anxiety in major depression: relationship to suicide attempts.
AB - OBJECTIVE: This study was an examination of the relationship of lifetime panic
disorder and anxiety symptoms at index hospitalization to a history of a suicide
attempt in patients with a major depressive episode. METHOD: A total of 272
inpatients with at least one major depressive episode, with or without a history
of a suicide attempt, were entered into the study. They were given structured
diagnostic interviews for axis I and axis II disorders. Suicide attempt history,
current psychopathology, and traits of aggression and impulsivity were also
assessed. RESULTS: The rates of panic disorder did not differ in the suicide
attempters and nonattempters. Agitation, psychic anxiety, and hypochondriasis
were more severe in the nonattempter group. A multivariate analysis confirmed
that this effect was independent of aggression and impulsivity. CONCLUSIONS:
Comorbid panic disorder in patients with major depression does not seem to
increase the risk for lifetime suicide attempt. The presence of greater anxiety
in the nonattempters warrants further investigation.
PMID- 11007716
TI - High vesicular monoamine transporter binding in asymptomatic bipolar I disorder:
sex differences and cognitive correlates.
AB - OBJECTIVE: It has been hypothesized that anomalies in monoaminergic function
underlie some of the manifestations of bipolar disorder. In this study the
authors examined the possibility that trait-related abnormalities in the
concentration of monoaminergic synaptic terminals may be present in patients with
asymptomatic bipolar disorder type I. METHOD: The concentration of a stable
presynaptic marker, the vesicular monoamine transporter protein (VMAT2), was
quantified with (+)[(11)C]dihydrotetrabenazine (DTBZ) and positron emission
tomography. Sixteen asymptomatic patients with bipolar I disorder who had a prior
history of mania with psychosis (nine men and seven women) and individually
matched healthy subjects were studied. Correlational analyses were conducted to
examine the relationship between regional VMAT2 binding, cognitive function, and
clinical variables. RESULTS: VMAT2 binding in the thalamus and ventral brainstem
of the bipolar patients was higher than that in the comparison subjects. VMAT2
concentrations in these regions correlated with performance on measures of
frontal, executive function. In addition, sex differences in VMAT2 binding were
detected in the thalamus of the bipolar patients; the male patients had higher
binding than the women. No sex differences in binding were observed in the
healthy comparison group. CONCLUSIONS: These initial results suggest that higher
than normal VMAT2 expression and, by extension, concentration of monoaminergic
synaptic terminals, may represent a trait-related abnormality in patients with
bipolar I disorder and that male and female patients show different patterns.
Also, VMAT2 concentrations may be associated with some of the cognitive deficits
encountered in euthymic bipolar disorder.
PMID- 11007717
TI - Factor analysis of the DSM-III-R borderline personality disorder criteria in
psychiatric inpatients.
AB - OBJECTIVE: The goal of this study was to examine the factor structure of the DSM
III-R criteria for borderline personality disorder in young adult psychiatric
inpatients. METHOD: The authors assessed 141 acutely ill inpatients with the
Personality Disorder Examination, a semistructured diagnostic interview for DSM
III-R personality disorders. They used correlational analyses to examine the
associations among the different criteria for borderline personality disorder and
performed an exploratory factor analysis. RESULTS: Cronbach's coefficient alpha
for the borderline personality disorder criteria was 0.69. A principal components
factor analysis with a varimax rotation accounted for 57.2% of the variance and
revealed three homogeneous factors. These factors were disturbed relatedness
(unstable relationships, identity disturbance, and chronic emptiness); behavioral
dysregulation (impulsivity and suicidal/self-mutilative behavior); and affective
dysregulation (affective instability, inappropriate anger, and efforts to avoid
abandonment). CONCLUSIONS: Exploratory factor analysis revealed three homogeneous
components of borderline personality disorder that may represent personality,
behavioral, and affective features central to the disorder. Recognition of these
components may inform treatment plans.
PMID- 11007719
TI - Selective relationship between prefrontal N-acetylaspartate measures and negative
symptoms in schizophrenia.
AB - OBJECTIVE: Certain cognitive, behavioral, and emotional deficits (so-called
negative symptoms) in patients with schizophrenia have often been attributed to
prefrontal cortical pathology, but direct evidence for a relationship between
prefrontal neuronal pathology and negative symptoms has been lacking. The authors
hypothesized that an in vivo measure of prefrontal neuronal pathology (N:
acetylaspartate [NAA] levels) in patients with schizophrenia would predict
negative symptoms. METHOD: Proton magnetic resonance spectroscopic imaging ((1)H
MRSI) and rating scales for negative and positive symptoms were used to study 36
patients with schizophrenia. Magnetic resonance spectra were analyzed as
metabolite ratios, and parametric correlations were performed. RESULTS: A
regionally selective negative correlation was found between prefrontal NAA
creatine ratio and negative symptom ratings in this group of patients with
schizophrenia. CONCLUSIONS: Lower prefrontal NAA-and by inference greater
neuronal pathology-predicted more severe negative symptoms in patients with
schizophrenia. These data demonstrate a relationship between an intraneuronal
measure of dorsolateral prefrontal cortex integrity and negative symptoms in vivo
and represent further evidence for the involvement of the dorsolateral prefrontal
cortex in negative symptoms associated with schizophrenia.
PMID- 11007718
TI - Brain activation patterns in schizophrenic and comparison volunteers during a
matched-performance auditory recognition task.
AB - OBJECTIVE: The biological characteristics of schizophrenia are often studied by
using functional imaging techniques. However, since volunteers with schizophrenia
routinely fail to perform as accurately or as quickly as healthy volunteers, it
is difficult to ascertain whether a particular deficit in blood flow to a brain
region is due to behavior or to the underlying illness. In this report,
investigators used an auditory recognition task to assess brain blood flow
patterns and behavioral correlates of schizophrenic patient volunteers trained on
the task. METHOD: Twelve healthy volunteers and 18 volunteers with schizophrenia
were trained to make tone frequency recognitions. Accuracy and stimuli were
matched between groups. Participants were required to press a button to indicate
whether a briefly presented tone was the high-frequency (1500 Hz) reference tone
or one of a lower frequency level (level chosen to elicit an 80% accuracy score).
Subjects underwent bolus [(15)O]H(2)O blood flow positron emission tomography
during inactive rest, a sensory motor control condition, and the decision task.
Blood flow patterns were assessed between conditions and between groups. RESULTS:
As a group, the patients with schizophrenia (who performed as quickly and
accurately as the comparison subjects) exhibited significantly less change in
regional cerebral blood flow (rCBF) to the anterior cingulate and supplementary
motor cortices when switching from the sensory motor control to the decision
condition. There were also marked between-group differences in correlations
between rCBF and response time. Whereas the comparison subjects exhibited
progressively greater blood flow to the frontal cortex in association with longer
response times, the schizophrenic patients exhibited progressively lower blood
flow in conjunction with extended response times. CONCLUSIONS: The failure to
appropriately enhance cingulate activity when engaged in a demanding task and the
progressive, time-dependent decline in frontal blood flow suggest that patients
with schizophrenia are unable to make optimal use of frontocingulate systems when
maximally engaged in high-error tasks.
PMID- 11007720
TI - Adult outcomes of child- and adolescent-onset schizophrenia: diagnostic stability
and predictive validity.
AB - OBJECTIVE: The goal of the study was to establish the predictive validity of a
diagnosis of schizophrenia in childhood and early adolescence by examining
diagnostic continuity into adult life and comparing social and symptomatic
outcomes of child- and adolescent-onset schizophrenia with those of
nonschizophrenic psychoses. METHOD: A total of 110 consecutive patients with
first-episode child- or adolescent-onset psychosis (mean age at onset=14.2 years)
presenting to the Maudsley Hospital in London between 1973 and 1991 were followed
up an average of 11.5 years after first contact. Ninety-three (84.5%) of 110
patients were successfully followed-up, 51 with a first-episode diagnosis of DSM
III-R schizophrenia and 42 with nonschizophrenic psychoses. Consensus best
estimate DSM-III-R diagnoses were made at follow-up, and course and outcome were
assessed blind to first-episode diagnosis. RESULTS: Diagnostic stability was high
for child- and adolescent-onset DSM-III-R schizophrenia (positive predictive
value=80%) and affective psychoses (positive predictive value=83%) but much lower
for schizoaffective and atypical psychoses. Compared with other psychoses, child-
or adolescent-onset schizophrenia was associated with significantly worse
symptomatic and social outcomes, which were characterized by a chronic illness
course and severe impairments in social relationships and independent living.
CONCLUSIONS: The diagnosis of DSM-III-R schizophrenia in childhood and
adolescence has good predictive validity. The high level of diagnostic stability
suggests etiological continuity with adult schizophrenia, with onset in childhood
and adolescence associated with a particularly malignant course and outcome.
PMID- 11007721
TI - Modulation of the startle response and startle laterality in relatives of
schizophrenic patients and in subjects with schizotypal personality disorder:
evidence of inhibitory deficits.
AB - OBJECTIVE: Patients with schizophrenia spectrum disorders have been shown to have
deficits in sensorimotor gating as assessed by prepulse inhibition of the startle
response. The authors hypothesized that nonschizophrenic relatives of patients
with schizophrenia would also have prepulse inhibition deficits, thereby
reflecting a genetically transmitted susceptibility to sensorimotor gating
deficits. METHOD: Twenty-five comparison subjects, 23 patients with
schizophrenia, 34 relatives of the schizophrenic patients, and 11 subjects with
schizotypal personality disorder were assessed in an acoustic startle paradigm.
The eye-blink component of the startle response was assessed bilaterally by using
electromyographic recordings of orbicularis oculi. RESULTS: The patients with
schizophrenia, their relatives, and subjects with schizotypal personality
disorder all had reduced prepulse inhibition relative to comparison subjects, and
these deficits were more evident in measures of right eye-blink prepulse
inhibition. Comparison subjects demonstrated greater right versus left eye-blink
prepulse inhibition, whereas the probands, their relatives, and subjects with
schizotypal personality disorder showed less asymmetry of prepulse inhibition.
CONCLUSIONS: These data suggest a genetically transmitted deficit in prepulse
inhibition (sensorimotor gating) in patients with schizophrenia spectrum
disorders, including subjects with schizotypal personality disorder and relatives
of patients with schizophrenia.
PMID- 11007722
TI - Relationship between climate and psychiatric inpatient length of stay in Veterans
Health Administration hospitals.
AB - OBJECTIVE: The study examined whether climate has an impact on inpatient
psychiatric length of stay in Veterans Health Administration hospitals (VHA).
METHOD: Data from the National Weather Service for eight climate variables for
the locations of 134 VHA hospitals nationwide were factor analyzed, resulting in
two climate factors representing temperature and precipitation. Factor scores
were correlated with psychiatric mean lengths of stay from 1994 to 1998 for 99
VHA hospitals with inpatient psychiatric services and for the 22 VHA regional
divisions (Veterans Integrated Service Networks). RESULTS: Climate factors
correlated modestly but significantly with length of stay, with correlations
ranging from -0. 25 to -0.37 at the hospital level and from -0.38 to -0.45 at the
VHA regional level; hospitals in warmer and drier climates had shorter lengths of
stay. Medical centers in colder climates had the longest lengths of stay in
winter and fall. The significant correlation between climate and length of stay
was not affected by recent reductions in length of stay in VHA hospitals.
CONCLUSIONS: Higher clinical costs associated with longer lengths of stay in
colder climates have implications for budget planning. Climate factors must also
be recognized for their potential effect on performance monitoring systems
focused on hospital utilization. Researchers must continue to consider broader
contextual variables such as climate if they are to fully understand the
determinants of health care utilization and psychiatric hospitalization costs.
PMID- 11007723
TI - Seasonal variation of violence in Norway.
AB - OBJECTIVE: Seasonal variations of violence have been the subject of some
controversy. Norway, situated between latitudes 58 degrees and 72 degrees N, has
considerable seasonal variations of light and provides a good opportunity for
studies of seasonality. METHOD: The monthly numbers of police reports of violent
incidents in 1991-1997 were obtained for the entire Norwegian population of
4,450,000 inhabitants and separately for each of seven Norwegian cities at
different latitudes. RESULTS: A total of 82,537 episodes of violence were
recorded. There was a significant variation in violent incidents between months,
with a minimum daily frequency of 28.7 in March and a maximum daily frequency of
35.1 in June. The frequency curve had one significant peak in May through June
and another significant peak in October through November. The monthly frequency
of violence correlated with the absolute value of monthly change in length of day
from the previous month. In the seven cities the highest monthly ratio of
observed to expected frequencies increased with latitude. With increasing
latitude, the months with the largest increase in violence came later both in the
spring and in the fall. CONCLUSIONS: There is a distinct pattern of seasonal
variation in the frequency of violence that varies systematically with latitude.
This pattern resembles the seasonal pattern of some forms of suicide,
hospitalization for affective disorders, and mood and activity in the general
population.
PMID- 11007724
TI - Associations between bipolar disorder and other psychiatric disorders during
adolescence and early adulthood: a community-based longitudinal investigation.
AB - OBJECTIVE: The study investigated cross-sectional and longitudinal associations
between bipolar disorder and other psychiatric disorders during adolescence and
early adulthood. METHOD: Psychiatric interviews were administered to a
representative community sample of 717 youths and their mothers in 1983 (mean age
of youths=14 years) and again in 1985-1986, and 1991-1993. RESULTS: A wide range
of psychiatric disorders co-occurred with bipolar disorder during adolescence and
early adulthood. Adolescent anxiety disorders were uniquely associated with
increased risk for early adulthood bipolar disorder after adolescent bipolar
disorder was accounted for. Manic symptoms during adolescence were associated
with increased risk for anxiety and depressive disorders during early adulthood
after adolescent anxiety and depressive disorders were accounted for.
CONCLUSIONS: Adolescents with anxiety disorders may be at increased risk for
bipolar disorder or clinically significant manic symptoms during early adulthood.
Adolescents with manic symptoms may be at increased risk for anxiety and
depressive disorders during early adulthood.
PMID- 11007725
TI - Elevation in late-life depression of intercellular adhesion molecule-1 expression
in the dorsolateral prefrontal cortex.
AB - OBJECTIVE: Late-life depression may be associated with vascular disease. The
authors investigated this association by determining whether intercellular
adhesion molecule-1 (ICAM-1), a marker of ischemia-induced inflammation, is
elevated in the dorsolateral prefrontal cortex in depression. METHOD: The authors
studied postmortem tissue from 20 depressed subjects and a matched comparison
group of 20 nondepressed subjects. They used immunocytochemistry to stain ICAM-1
in blood vessels on sections of the dorsolateral prefrontal cortex and occipital
cortex and quantitative true color image analysis to measure the proportion of
vessels expressing ICAM-1. RESULTS: ICAM-1 was significantly higher in both the
gray and white matter of the depressed subjects' dorsolateral prefrontal cortex
than the comparison subjects' dorsolateral prefrontal cortex. The difference
between these groups was much smaller in the gray and white matter of the
occipital cortex. CONCLUSIONS: These findings support the vascular depression
hypothesis, which has important implications for the understanding and management
of late-life depression.
PMID- 11007726
TI - Use of no-suicide contracts by psychiatrists in Minnesota.
AB - OBJECTIVE: The no-suicide contract is widely recommended as an important
intervention in the care of suicidal patients; however, there are no data
demonstrating its effectiveness or its acceptance in the professional community.
This study examines the use of no-suicide contracts by psychiatrists in
Minnesota. METHOD: A postcard questionnaire was mailed to 514 psychiatrists in
Minnesota inquiring about their practices and experiences with no-suicide
contracts. RESULTS: There were 267 responses, yielding a response rate of 52%. No
suicide contracts were used by 152 (57%) of the respondents. Within this group,
62 (41%) of the psychiatrists had patients who committed suicide or made serious
attempts after entering into a no-suicide contract. CONCLUSIONS: Among the
respondents to the questionnaire, slightly more than half used no-suicide
contracts, indicating that such contracts are not universally accepted as
standard practice among these psychiatrists. More data are needed to determine
the effectiveness of no-suicide contracts in preventing suicide.
PMID- 11007727
TI - Randomized, placebo-controlled, double-blind clinical trial of sertraline in the
treatment of depression complicating Alzheimer's disease: initial results from
the Depression in Alzheimer's Disease study.
AB - OBJECTIVE: This study evaluated the efficacy and safety of sertraline in the
treatment of major depression in 22 outpatients with Alzheimer's disease. METHOD:
Twelve of the 22 patients were given sertraline and 10 were given placebo by
random group assignment for 12 weeks. Response to treatment was measured by using
the Cornell Scale for Depression in Dementia. The patients were also assessed
with the Hamilton Depression Rating Scale, the activities of daily living
subscale of the Psychogeriatric Dependency Rating Scales, and the Mini-Mental
State. RESULTS: After 12 weeks of double-blind, placebo-controlled treatment,
nine of the patients given sertraline and two of those given placebo were at
least partial responders. Patients given sertraline had significantly greater
mean declines from baseline in Cornell Scale for Depression in Dementia scores;
the bulk of antidepressant response occurred by the third week of treatment.
CONCLUSIONS: Sertraline is superior to placebo in reducing depression in patients
with Alzheimer's disease who also suffer from major depression.
PMID- 11007728
TI - Thyroid hormone levels and recurrence of major depression.
AB - OBJECTIVE: The relationship between basal thyroid hormone levels and acute
antidepressant response has been studied, but any relationship between basal
thyroid hormone levels and long-term course of depressive illness has not been
evaluated. METHOD: The authors used a Cox regression survival analysis to
evaluate the relationship between life course of depressive illness and basal
levels of thyroid hormones (triiodothyronine [T(3)], thyroxine [T(4)], and
thyrotropin) in 75 outpatients with unipolar major depressive disorder. RESULTS:
Time to recurrence of major depression was inversely related to T(3) levels but
not to T(4) levels. CONCLUSIONS: These data may be of clinical interest in view
of the fact that T(3) is used to augment antidepressant response.
PMID- 11007729
TI - Functional anatomy of auditory verbal imagery in schizophrenic patients with
auditory hallucinations.
AB - OBJECTIVE: This study investigated the functional neuroanatomy of inner speech
and auditory verbal imagery in schizophrenic patients predisposed to auditory
hallucinations. METHOD: Eight patients with schizophrenia with a history of
prominent auditory hallucinations and six comparison subjects underwent
functional magnetic resonance imaging while generating inner speech or imagining
external speech. RESULTS: Patients showed no differences while generating inner
speech but experienced a relatively attenuated response in the posterior
cerebellar cortex, hippocampi, and lenticular nuclei bilaterally and the right
thalamus, middle and superior temporal cortex, and left nucleus accumbens during
auditory verbal imagery. CONCLUSIONS: Patients with schizophrenia who were prone
to auditory hallucinations show attenuated activation when processing inner
speech in areas implicated in verbal self-monitoring.
PMID- 11007730
TI - Preliminary evidence of improved verbal working memory performance and
normalization of task-related frontal lobe activation in schizophrenia following
cognitive exercises.
AB - OBJECTIVE: The authors' goal was to evaluate the possibility of treating brain
and behavioral aspects of verbal memory dysfunction in patients with
schizophrenia through cognitive exercises. METHOD: Eight patients did daily
verbal memory exercises that became progressively more difficult over a 10-week
training period. Memory performance and regional brain activations during a
verbal memory task were assessed before and after these exercises. RESULTS:
Verbal but not nonverbal memory performance improved after training; three
patients made substantial gains, and five showed little change. Performance gains
were correlated with increases in task-related activation of the left inferior
frontal cortex. One patient given 5 extra weeks of training 6 weeks after the
initial training period showed maintenance of initial performance gains 6 weeks
after training, further improvement after the second period of training, and
normalization of task-related activation of the left inferior frontal cortex.
CONCLUSIONS: Verbal memory deficits can be ameliorated by memory exercises in
some patients with schizophrenia. Performance improvements are associated with
increased task-related activation of the same brain region that is activated
during verbal memory tasks in healthy individuals.
PMID- 11007731
TI - Effects of methylphenidate on functional MRI blood-oxygen-level-dependent
contrast.
AB - OBJECTIVE: The authors' goal was to determine potential hemodynamic consequences
of methylphenidate on functional magnetic resonance imaging (MRI) blood-oxygen
level-dependent (BOLD) contrast. METHOD: BOLD and perfusion changes were recorded
from the motor cortex of six healthy subjects while they performed flexion
extension movements of the right index finger (finger tapping) at varying rates
before and after oral methylphenidate administration. RESULTS: Functional MRI
signals increased monotonically with faster movement rates. Subjects' heart rates
increased modestly after methylphenidate administration, but no changes in finger
tapping performance or functional MRI signals were observed. CONCLUSIONS:
Methylphenidate does not alter BOLD neural-hemodynamic coupling. Consequently,
functional MRI can be used to map neural systems that subserve cognitive
operations (e.g., attention and executive processes) in subjects taking
methylphenidate.
PMID- 11007733
TI - High doses of levothyroxine for refractory rapid cycling.
PMID- 11007732
TI - Prediction of dopamine transporter binding availability by genotype: a
preliminary report.
AB - OBJECTIVE: Evidence of a relationship between genotype and binding availability
was assessed for the dopamine and serotonin transporter genes. METHOD: The
authors assessed dopamine transporter genotype at the SLC6A3 3' variable number
of tandem repeats (VNTR) polymorphism and serotonin transporter genotype at the
SLC6A4 promotor VNTR polymorphism in 30 healthy subjects who also underwent
single photon emission computed tomography with [(123)I]beta-CIT. RESULTS:
Subjects homozygous for the 10-repeat allele at the SLC6A3 locus demonstrated
significantly lower dopamine transporter binding than carriers of the nine-repeat
allele. There was no effect of SLC6A4 genotype upon serotonin transporter
binding. CONCLUSIONS: These findings suggest that genetic variation at the SLC6A3
3' VNTR polymorphism may modify dopamine transporter function.
PMID- 11007735
TI - Agranulocytosis associated with lamotrigine.
PMID- 11007736
TI - Delirium with autoimmune thyroiditis induced by interferon alpha.
PMID- 11007737
TI - Citalopram and haloperidol for psychotic depression.
PMID- 11007738
TI - gamma-Hydroxybutyrate withdrawal and chloral hydrate.
PMID- 11007739
TI - Adenosine and antidepressant effects of sleep deprivation.
PMID- 11007740
TI - Psychological defense styles and childhood sexual abuse.
PMID- 11007741
TI - Measuring dopamine D(2) receptors.
PMID- 11007744
TI - Serotonin 2A receptor polymorphisms and [(3)H]Ketanserin binding.
PMID- 11007745
TI - Treatment of patients with delirium.
PMID- 11007754
TI - Immunological transitions in response to antigenic mutation during viral
infection.
AB - Antigenic variation is an important factor in viral persistence and disease
progression. We analyze immunological changes which occur in response to
antigenic mutation during chronic viral infection. Using an established model of
viral and immune system dynamics, we determine which qualitative shifts in the
immune response can be elicited by the appearance of a new mutant. We find that
antigenic mutation can cause dramatic shifts in the magnitude and type of anti
viral immune response. For example, the appearance of a mutant can elicit a new
immune response which recognizes the original viral strain. We also find that
novel strains of the virus which replicate more slowly than existing viral
strains are able to invade and survive, even when the immune system is capable of
mounting an immune response against the mutant.
PMID- 11007755
TI - Tumor necrosis factor receptor-1 is critically involved in the development of
experimental autoimmune myasthenia gravis.
AB - Tumor necrosis factor receptor-1 (TNFR1, CD120a) has been implicated in the
pathogenesis of several experimental models of T cell-mediated autoimmune
disorders, but its role in antibody-mediated autoimmune diseases has not been
addressed. Experimental autoimmune myasthenia gravis (EAMG), an autoantibody
mediated T cell-dependent neuromuscular disorder, represents an animal model for
myasthenia gravis in human. To investigate the role of TNFR1 in the pathogenesis
of EAMG, TNFR1(-/-) and wild-type mice were immunized with TORPEDO: acetylcholine
receptor (AChR) in complete Freund's adjuvant. TNFR1(-/-) mice failed to develop
EAMG. Lymphoid cells from TNFR1(-/-) mice produced low amounts of T(h)1 (IFN
gamma, IL-2 and IL-12)-type cytokines, but elevated levels of T(h)2 (IL-4 and IL
10)-type cytokines compared with lymphoid cells of wild-type mice. Accordingly,
the levels of anti-AChR IgG2 antibodies were severely reduced and the level of
anti-AChR IgG1 antibodies were moderately reduced. Co-injection of recombinant
mouse IL-12 with AChR in adjuvant restored T cell responses to AChR and promoted
development of EAMG in TNFR1(-/-) mice. These results demonstrate that the
TNF/TNFR1 system is required for the development of EAMG. The lack of a
functional TNF/TNFR1 system can, at least in part, be substituted by IL-12 at the
stage of initial priming with AChR and adjuvant.
PMID- 11007756
TI - The Pim-1 kinase stimulates maturation of TCRbeta-deficient T cell progenitors:
implications for the mechanism of Pim-1 action.
AB - We demonstrate that overexpression of Pim-1, a cytoplasmic serine/threonine
kinase of poorly defined function, results in the development of substantial
numbers of CD4(+)CD8(+) double-positive thymocytes in two independent knock-out
mouse models (i.e. the RAG-1-deficient and TCRbeta gene enhancer-deleted mice) in
which production of a functionally rearranged TCRbeta gene (hence the pre-TCR) is
impaired. This activity of Pim-1, however, does not affect signaling through the
Ras/Raf/MAP kinase cascade nor signaling which mediates suppression of TCRbeta
gene recombination (i.e. allelic exclusion). While overexpression of Pim-1
positively affects cell cycle progression in selected CD4(-)CD8(-) double
negative precursors, it did not affect expression of components of the cell cycle
machinery, with the exception of the G(1)-specific phosphatase Cdc25A upon
antigen receptor stimulation. We propose that Pim-1 acts downstream, or in
parallel, to pre-TCR-mediated selection as one factor involved in the
proliferative expansion of beta-selected pre-T cells.
PMID- 11007757
TI - Identification and characterization of a molecule, BAM11, that associates with
the pleckstrin homology domain of mouse Btk.
AB - Bruton's tyrosine kinase (Btk) is required for normal B cell development and
signal transduction through cell surface molecules, and its defects lead to X
linked immune deficiency in mice and X-linked agammaglobulinemia in humans. In
this report, we will describe the identification and characterization of a
molecule, BAM11, which binds to the pleckstrin homology domain of Btk. A sequence
homology search revealed that BAM11 has 89% homology, at the amino acid level, to
human LTG19/ENL, that was originally identified as one of the fusion partners
involved in chromosomal translocations of 11q23, MLL/ALL-1/HRX, in leukemia
cells. Deletion mutants demonstrated that the region of BAM11 required for
binding to Btk was localized between amino acid residues 240 and 256. Forced
expression of a truncated form of BAM11 (amino acids 246-368) inhibited IL-5
induced proliferation by 50%, whereas forced expression of full-length BAM11 in
Y16 cells did not affect the IL-5 responsiveness. We have also shown that BAM11
(amino acids 246-368) inhibited the kinase activity of Btk. These results suggest
that the binding of BAM11 to Btk plays a regulatory role in the Btk signal
transduction pathway. A cell fractionation study and analysis using EGFP-fused
Btk protein demonstrated that a proportion of Btk is present within the nucleus.
PMID- 11007758
TI - Blocked transport of soluble K(b) molecules containing connecting peptide segment
involved in calnexin association.
AB - The molecular event governing the assembly of the MHC class I heavy chain-beta(2)
microglobulin-peptide complex is still not fully understood. In order to
characterize the transport properties of MHC class I molecules, several truncated
H-2K(b) genes were constructed and expressed in COS7 cells. Surprisingly, the
expressed soluble molecule containing connecting peptide (CP) segment (sK(b)(CP))
did not secrete as efficiently as the one without CP (sK(b)(CYT)). When the
sK(b)(CP) gene was transfected into a calnexin-deficient cell line CEM.NK(R), the
amount of soluble K(b) molecules in the supernatant was comparable with
sK(b)(CYT)-transfected CEM.NK(R). To further demonstrate the different transport
of sK(b)(CP) and sK(b)(CYT) within living cells, we attached green fluorescent
protein (GFP) to the C-termini of both molecules and, as a comparison, to the
full-length transmembrane counterpart (mK(b)-GFP). While the mK(b)-GFP
transfected cells showed the green fluorescence in the reticular network and the
nuclear envelope, sK(b)(CP)-GFP showed obviously lump fluorescence of high
intensity within cells. However, the distribution of sK(b)(CYT)-GFP was fairly
uniform. Furthermore, GFP-tagged molecules allow us to analyze their interaction
with other proteins in a direct, simple and quantitative method, designated
immunofluorescence precipitation. The results showed that 60% of sK(b)(CP)-GFP
molecules were associated with calnexin, while <10% with tapasin. Taken together
with the results from sK(b)(CYT)-GFP and mK(b)-GFP, it is reasonable to deduce
that the CP segment is involved in the association of class I molecules with
calnexin and the transmembrane region might play a dynamic role in the
dissociation from calnexin. The suggested kinetic association of class I
molecules with calnexin is likely to contribute to the different maturation rate
between several class I alleles.
PMID- 11007759
TI - Negative regulation of B cell receptor-mediated signaling in B-1 cells through
CD5 and Ly49 co-receptors via Lyn kinase activity.
AB - CD5(+) B-1 cells are known to be unresponsive to B cell receptor (BCR)-mediated
growth signals but instead undergo apoptosis. However, the B-1 cells from Lyn
kinase-deficient (Lyn-/-) mice exhibited an enhanced proliferative response upon
BCR cross-linking. It has been reported that BCR-mediated signaling in B-1 cells
is negatively regulated by signals from CD22, CD5 and CD72 co-receptors, and that
Lyn kinase plays a crucial role in tyrosine phosphorylation of immunoreceptor
tyrosine-based inhibitory motifs on the CD22 and CD72, which recruits SHP-1 to
the BCR complex. We found that Lyn kinase is also essential for the tyrosine
phosphorylation of CD5 and subsequent recruitment of SHP-1 in B-1 cells upon
cross-linking of BCR. Moreover, a distinct subpopulation of B-1 cells was found
to express cell surface Ly49, which is known as a MHC class I-binding negative
regulatory receptor on NK cells. Ly49 was rapidly tyrosine phosphorylated upon
cross-linking of BCR and SHP-1 was found to recruit to the phosphorylated Ly49.
Addition of F(ab')(2) fragments of anti-Ly49 antibodies partially blocked
negative signals in B-1 cells. Thus two co-receptors, CD5 and Ly49, which are
unique to B-1 cells, play a role in the regulation of B-1 cell activation. These
results indicate that BCR-mediated signals in B-1 cells are strictly and
negatively regulated through multiple pathways, that are dependent on Lyn kinase
activity.
PMID- 11007760
TI - Contribution of H-2 and non-H-2 genes in the control of mercury-induced
autoimmunity.
AB - Mercury-induced autoimmunity is characterized by a T cell-dependent B cell
activation (mainly of IgG1 and IgE isotypes), production of anti-nucleolar
autoantibodies (ANolA) and the formation of renal IgG deposits. The autoimmunity
is to a large extent controlled by genetic factors. We studied 15 different
inbred mouse strains of seven H-2 (mouse MHC) genotypes to determine the
importance of H-2 and non-H-2 background genes in mercury-induced autoimmunity.
The tested strains exhibited a diverse autoimmune response to mercury. In each H
2 genotype, there was at least one strain which responded to mercury by the
production of high levels of IgG1 and IgE Ig as well as by the development of
high titers of renal IgG1 deposits. Only mouse strains with H-2(s) and H-2(q)
genotypes, irrespective of their background genes, produced ANolA after mercury
treatment. Only SJL (H-2(s)) and A.SW (H-2(s)) mice were highly susceptible to
all characteristics of mercury-induced autoimmunity. NZB (H-2(d)) mice were also
highly susceptible, but they did not develop ANolA. Only the DBA/2 (H-2(d))
strain was found to be resistant to all tested mercury-induced autoimmune
manifestations, suggesting that non-responsiveness to mercury in DBA/2 mice was
largely influenced by non H-2 genes. These findings imply that H-2 genes mainly
determine the susceptibility to mercury-induced ANolA production, whereas non-H-2
genes control the susceptibility to and the severity of the B cell activation and
renal IgG deposition.
PMID- 11007761
TI - Differences in specificities of anti-centromere sera for the monomeric and
dimeric C-terminal peptides of human centoromere protein C.
AB - Centromere protein-C (CENP-C), one of the centromere autoantigens and components
of the inner plate of the kinetochore, is suggested to make a dimer at the C
terminus. In order to investigate the presence of conformation-specific anti
centromere antibodies (ACA) to the dimer form, the C-terminal 124 amino acids (CF
124) were expressed in Escherichia coli, affinity purified and chemically cross
linked. Immunoblotting was utilized to compare the reactivities between the
dimers and the monomers against 58 ACA(+) sera. The reactivities of the dimers
were obviously higher in both IgG and IgM responses. The dimer was still more
reactive than the glutathione S-transferase-fused monomer in some sera. Two kinds
of CF-124 mutant (each contained one amino acid change at the N-terminal region
of CF-124) and two cut segments of CF-124 (67 N-terminal amino acids and 58 C
terminal amino acids) were also examined. The former two mutants decreased the
dimerization activity. The latter two mutants lost both activities except for the
faint dimerization activity of the N-terminal half. Affinity-purified antibodies
with CF-124 in a liquid phase containing the co-purified GroE protein of E. coli,
GroEL, reacted to the centromere in culture cells. In conclusion, there are
heterogeneous autoepitopes including some conformational epitopes at the C
terminal CENP-C.
PMID- 11007762
TI - Characterization of a new human B7-related protein: B7RP-1 is the ligand to the
co-stimulatory protein ICOS.
AB - Optimal T cell activation requires the interactions of co-stimulatory molecules,
such as those in the CD28 and B7 protein families. Recently, we described the co
stimulatory properties of the murine ligand to ICOS, which we designated as B7RP
1. Here, we report the co-stimulation of human T cells through the human B7RP-1
and ICOS interaction. This ligand-receptor pair interacts with a K:(D)
approximately 33 nM and an off-rate with a t((1/2)) > 10 min. Interestingly,
tumor necrosis factor (TNF)-alpha differentially regulates the expression of
human B7RP-1 on B cells, monocytes and dendritic cells (DC). TNF-alpha enhances
B7RP-1 expression on B cells and monocytes, while it inhibits it on DC. The human
B7RP-1-Fc protein or cells that express membrane-bound B7RP-1 co-stimulate T cell
proliferation in vitro. Specific cytokines, such as IFN-gamma and IL-10, are
induced by B7RP-1 co-stimulation. Although IL-2 levels are not significantly
increased, B7RP-1 co-stimulation is dependent on IL-2. These experiments define
the human ortholog to murine B7RP-1 and characterize its interaction with human
ICOS.
PMID- 11007763
TI - Oral administration of cholera toxin B subunit conjugated to myelin basic protein
protects against experimental autoimmune encephalomyelitis by inducing
transforming growth factor-beta-secreting cells and suppressing chemokine
expression.
AB - The efficacy and mechanism of immunosuppression against experimental autoimmune
encephalomyelitis (EAE) by oral low-dose administration of myelin basic protein
(MBP) conjugated to cholera toxin B subunit (CTB) were investigated in Lewis rats
immunized with MBP together with complete Freund's adjuvant 4 days before the
start of treatment. Oral treatment with CTB-MBP conjugate gave almost complete
protection against disease, an effect that was totally abrogated by including a
low dose of cholera holotoxin (CT). The protection by CTB-MBP was associated with
a dramatic reduction in the number of leukocytes staining for CD4, CD8, IL-2R or
MHC class II in the spinal cord as examined by immunohistochemistry. The mRNA
expressions of T(h)1 cytokines IFN-gamma, IL-12 and tumor necrosis factor-alpha,
as well as of chemokines monocyte chemotactic protein (MCP)-1 and RANTES in the
spinal cord were also reduced by 76-94%, as assessed by in situ hybridization. In
contrast, transforming growth factor (TGF)-beta mRNA-expressing cells were
strongly increased in the spinal cord from animals treated orally with the CTB
MBP conjugate. In the draining peripheral lymph nodes, the number of MBP-specific
TGF-beta mRNA-expressing cells was also increased, whereas there was a decrease
in cells expressing T(h)1 or T(h)2 cytokine mRNA. Protection against EAE could be
transferred by injection of cells from the mesenteric lymph nodes of animals fed
with CTB-MBP into naive animals exposed to encephalitogenic T cells. The results
indicate that the protective anti-inflammatory effect by oral treatment with CTB
MBP conjugate is, to a large extent, due to the induction of TGF-beta-secreting
suppressive-regulatory T cells and to local down-regulation of MCP-1 and RANTES
in the spinal cord.
PMID- 11007764
TI - The level of expression of mu heavy chain modifies the composition of peripheral
B cell subpopulations.
AB - The B cell receptor (BCR) has a decisive role in transducing signals required for
the development of B cells and their survival in the periphery. However, the
processes that initiate these signals remain unclear and concepts of constitutive
and ligand-dependent signaling have been proposed. Using a mu-transgenic mouse
model, we have analyzed the impact of high surface IgM expression on the
composition of the splenic B cell population. kappa-deficient mice homozygous for
the H3-mu transgene have B cells with a higher BCR surface density than H3
heterozygous mice. This higher BCR expression is associated with an increase in
the percentage and the total number of splenic B cells. In addition, an important
proportion of CD23(-)CD21(+) marginal zone (MZ) B cells can be observed in H3
homozygous mice. However, these modifications operate in the absence of
impairment of the positive selection process of the H3-mu/lambda1 combination
over the H3-mu/lambda2 + 3 ones. These results suggest that (i) a constitutive
BCR signaling directly correlated with BCR surface density is responsible for the
efficient B cell colonization of the periphery with an accumulation of B cells in
the MZ and (ii) a ligand-dependent BCR signal is responsible for the clonotype
composition of the mature B cell repertoire.
PMID- 11007765
TI - Neonatal induction of tolerance to T(h)2-mediated autoimmunity in rats.
AB - Brown-Norway (BN) rats are highly susceptible to drug-induced immune
dysregulations and when injected with mercuric chloride (HgCl(2)) or sodium
aurothiopropanolsulfonate (ATPS), they develop a syndrome characterized by a
polyclonal B cell activation depending upon CD4(+) T(h)2 cells that recognize
self-MHC class II molecules. Since peripheral tolerance of T(h)2 cells might be
crucial in the prevention of immunological manifestations such as allergy,
establishing conditions for inducing tolerance to HgCl(2)- or ATPS-mediated
immune manifestations appeared to be of large interest. We report here that BN
rats neonatally injected with HgCl(2): (i) do not develop the mercury disease,
(ii) remain resistant to HgCl(2)-induced autoimmunity at 8 weeks of age and
later, provided they are regularly exposed to HgCl(2), (iii) are still
susceptible to ATPS-induced immune manifestations, and (iv) exhibit spleen cells
that adoptively transfer tolerance to HgCl(2)-induced autoimmunity in naive,
slightly irradiated, syngeneic recipients. These findings demonstrate that
dominant specific tolerance can be neonatally induced using a chemical otherwise
responsible for T(h)2-mediated autoimmunity.
PMID- 11007766
TI - In vivo cytotoxicity of the prion protein fragment 106-126.
AB - Transmissible spongiform encephalopathies are fatal neurological diseases
characterized by astroglyosis, neuronal loss, and by the accumulation of the
abnormal isoform of the prion protein. The amyloid prion protein fragment 106-126
(P106-126) has been shown to be toxic in cultured hippocampal neurons (). Here,
we show that P106-126 is also cytotoxic in vivo. Taking advantage of the fact
that retina is an integral part of the central nervous system, the toxic effect
of the peptide was investigated by direct intravitreous injection. Aged solutions
of P106-126 induced apoptotic-mediated retinal cell death and irreversibly
altered the electrical activity of the retina. Neither apoptosis nor
electroretinogram damages were observed with freshly diluted P106-126, suggesting
that the toxicity is linked to the aggregation state of the peptide. The retina
provides a convenient in vivo system to look for potential inhibitors of
cytotoxicity associated with spongiform encephalopathies.
PMID- 11007767
TI - A positive role for the PP2A catalytic subunit in Wnt signal transduction.
AB - Protein phosphatase-2A (PP2A) is a multisubunit serine/threonine phosphatase
involved in intracellular signaling, gene regulation, and cell cycle progression.
Different subunits of PP2A bind to Axin and Adenomatous Polyposis Coli,
components of the Wnt signal transduction pathway. Using early Xenopus embryos,
we studied how PP2A functions in Wnt signal transduction. The catalytic subunit
of PP2A (PP2A-C) potentiated secondary axis induction and Siamois reporter gene
activation by Dishevelled, a component of the Wnt pathway, indicating a positive
regulatory role of this enzyme in Wnt signaling. In contrast, small t antigen, an
antagonist of PP2A-C, inhibited Dishevelled-mediated signal transduction, as did
the regulatory PP2A-B'epsilon subunit, consistent with the requirement of PP2A
function in this pathway. Although Wnt signaling is thought to occur via
regulation of beta-catenin degradation, PP2A-C did not significantly affect beta
catenin stability. Moreover, the pathway activated by a stabilized form of beta
catenin was sensitive to PP2A-C and its inhibitors, suggesting that PP2A-C acts
downstream of beta-catenin. Because previous work has suggested that PP2A can act
upstream of beta-catenin, we propose that PP2A regulates the Wnt pathway at
multiple levels.
PMID- 11007768
TI - Reversal of autocrine and paracrine effects of interleukin 1 (IL-1) in human
arthritis by type II IL-1 decoy receptor. Potential for pharmacological
intervention.
AB - Interleukin 1 (IL-1), produced by both synovial cells and chondrocytes, plays a
pivotal role in the pathogenesis of cartilage destruction in osteoarthritis (OA).
We examined the specific expression and function of IL-1 receptor family-related
genes in human joint tissues. Gene array analysis of human normal and OA-affected
cartilage showed mRNA expression of IL-1 receptor accessory protein (IL-1RAcp)
and IL-1 type I receptor (IL-1RI), but not IL-1 antagonist (IL-1ra) and IL-1 type
II decoy receptor (IL-1RII). Similarly, human synovial and epithelial cells
showed an absence of IL-1RII mRNA. Functional genomic analyses showed that
soluble (s) IL-1RII, at picomolar concentrations, but not soluble TNF
receptor:Fc, significantly inhibited IL-1beta-induced nitric oxide (NO) and/or
prostaglandin E(2) production in chondrocytes, synovial and epithelial cells. In
OA-affected cartilage, the IC(50) for inhibition of NO production by sIL-1RII was
2 log orders lower than that for sIL-1RI. Human chondrocytes that overexpressed
IL-1RII were resistant to IL-1-induced IL-1beta mRNA accumulation and inhibition
of proteoglycan synthesis. In osteoarthritis, deficient expression by
chondrocytes of innate regulators or antagonists of IL-1 such as IL-1ra and IL
1RII (soluble or membrane form) may allow the catabolic effects of IL-1 to
proceed unopposed. The sensitivity of IL-1 action to inhibition by sIL-1RII has
therapeutic implications that could be directed toward correcting this
unfavorable tissue(s) dependent imbalance.
PMID- 11007769
TI - Goodpasture antigen-binding protein, the kinase that phosphorylates the
goodpasture antigen, is an alternatively spliced variant implicated in autoimmune
pathogenesis.
AB - The non-collagenous C-terminal domain of the alpha(3) chain of collagen IV is the
autoantigen in Goodpasture disease, an autoimmune disorder described only in
humans. Specific N-terminal phosphorylation is a biological feature unique to the
human domain when compared with other homologous domains lacking immunopathogenic
potential. We have recently cloned from a HeLa-derived cDNA library a novel
serine/threonine kinase (Goodpasture antigen-binding protein (GPBP)) that
phosphorylates the N-terminal region of the human domain (Raya, A. Revert, F,
Navarro, S. and Saus J. (1999) J. Biol. Chem. 274, 12642-12649). We show here
that the pre-mRNA of GPBP is alternatively spliced in human tissues and that the
most common transcript found encodes GPBPDelta26, a molecular isoform devoid of a
26-residue serine-rich motif. Recombinantly expressed GPBPDelta26 exhibits lower
activity than GPBP, due at least in part to a reduced ability of GPBPDelta26 to
interact and to form very active high molecular weight aggregates. In human
tissues, GPBP shows a more limited expression than GPBPDelta26 but displays a
remarkable preference for the small vessels and for histological structures
targeted by natural autoimmune responses including alveolar and glomerular
basement membranes, the two main targets in Goodpasture disease. GPBP expression
is, in turn, up-regulated in the striated muscle of a Goodpasture patient and in
other autoimmune conditions including cutaneous lupus erythematosus, pemphigoid,
and lichen planus.
PMID- 11007770
TI - Synergistic cooperation between Sp1 and Smad3/Smad4 mediates transforming growth
factor beta1 stimulation of alpha 2(I)-collagen (COL1A2) transcription.
AB - Transforming growth factor-beta1 (TGFbeta) is a strong activator of extracellular
matrix accumulation. TGFbeta stimulates the gene coding for human alpha2(I)
collagen (COL1A2) by inducing binding of an Sp1-containing complex to an upstream
promoter element (TGFbeta responsive element or TbRE) that contains a CAGA box.
Here we report that the CAGA box of the TbRE is the binding site of the
Smad3/Smad4 complex, and that the binding of the complex is required for TGFbeta
induced COL1A2 up-regulation. Recombinant Smad3 and Smad4 bind in vitro to the
CAGA box of COL1A2; TGFbeta treatment of cultured fibroblasts induces Smad3/Smad4
binding to the TbRE; transient overexpression of Smad3 and Smad4 in fibroblasts
transactivates TbRE-driven transcription; and COL1A2 gene up-regulation by
TGFbeta is abolished in cells stably transfected with plasmids that express
dominant negative forms of Smad3 or Smad4. In Sp1-deficient Drosophila Schneider
cells, there was cooperative synergy between Smad3/Smad4 and Sp1 at the TbRE
site. The analysis also emphasized the requirement of both Sp1- and Smad-binding
sites for optimal promoter transactivation. In cells stably transfected with a
plasmid expressing a dominant negative form of Sp1, the synergy was shown to be
promoter-specific and dependent on the binding of Sp1 to the TbRE. Interestingly,
overexpression of dominant negative Sp1 was found to block the antagonistic
signal of tumor necrosis factor-alpha on COL1A2 transcription, as well. These
results provide the first linkage between the Smad3 and Smad4 proteins and
TGFbeta stimulation of type I collagen biosynthesis.
PMID- 11007771
TI - Cell adhesion regulates ubiquitin-mediated degradation of the platelet-derived
growth factor receptor beta.
AB - Cross-talk between integrin-mediated adhesion and growth factors has been
described in many recent studies; however, the underlying mechanisms remain
incompletely understood. We report here that detachment of cells from the
extracellular matrix induced a decrease in both the autophosphorylation and
protein levels of the platelet-derived growth factor receptor beta (PDGF-R beta),
which was completely reversed upon replating cells on fibronectin. The effect
occurred in all cells examined but to a greater extent in primary fibroblasts
compared with established cell lines. Decreased PDGF-R levels in suspended cells
correlated with ubiquitination of the PDGF-R and was blocked by treatment with
inhibitors of the proteasome pathway. Unlike PDGF-induced down-regulation,
detachment-induced degradation did not require receptor autophosphorylation,
internalization, or tyrosine kinase activity. We conclude that cell detachment
results in cellular desensitization to PDGF that is mediated by degradation of
the PDGF-R via a novel ubiquitin-dependent pathway.
PMID- 11007772
TI - Expression of constitutively active phosphatidylinositol 3-kinase inhibits
activation of caspase 3 and apoptosis of cardiac muscle cells.
AB - Apoptosis of cardiac muscle cells contributes to the development of
cardiomyopathy. Recent studies showed that insulin-like growth factor I (IGF-I)
inhibits apoptosis of cardiac muscle cells and improves myocardial function in
experimental heart failure. This study was carried out to elucidate the role of
phosphatidylinositol 3-kinase (PI 3-kinase) in the anti-apoptotic actions of IGF
I in cardiomyocytes and to explore whether expression of constitutively active PI
3-kinase can inhibit apoptosis in cardiomyocytes. Apoptosis of primary
cardiomyocytes was induced by doxorubicin treatment and serum withdrawal.
Transduction of cardiomyocytes with constitutively active PI 3-kinase
specifically lead to serine phosphorylation of Akt, whereas phosphorylation of
IGF-I receptor, IRS1/2 and p44/42 mitogen-activated protein kinase were not
increased. In the cardiomyocytes transduced with constitutively active PI 3
kinase, activation of the pro-apoptotic caspase 3 was attenuated and
fragmentation of DNA was reduced. Preincubating cells with PI 3-kinase inhibitor
LY294002 was associated with loss of anti-apoptotic actions of IGF-I and PI 3
kinase. Neither IGF-I nor constitutively active PI 3-kinase lead to serine
phosphorylation of Bad, suggesting that the anti-apoptotic effects of PI 3-kinase
are not mediated through Bad phosphorylation in cardiac muscle cells. To
determine whether activation of caspase 3 is sufficient to induce apoptosis in
cardiomyocytes, an engineered TAT-caspase 3 protein was introduced to
cardiomyocytes. Significant reduction of cell viability occurred in the
cardiomyocytes transduced with active caspase 3, indicating that activation of
caspase 3 is sufficient to cause cardiomyocyte death. These findings indicate the
existence of an IGF-I receptor-PI 3-kinase-caspase 3 pathway in cardiomyocytes
that plays an important role in the anti-apoptotic actions of IGF-I in heart.
Moreover, these data suggest that modulation of PI 3-kinase activities may
represent a potential therapeutic strategy to counteract the occurrence of
apoptosis in cardiomyopathy.
PMID- 11007773
TI - Transcriptional activities of reovirus RNA polymerase in recoated cores.
Initiation and elongation are regulated by separate mechanisms.
AB - The particle-associated reovirus polymerase synthesizes mRNA within only certain
viral particle types. Reovirus cores, subviral particles lacking outer capsid
proteins mu1, sigma3, and sigma1, produce mRNA and abortive transcripts. Reovirus
virions, which contain complete outer capsids, cannot produce mRNA and produce
few abortive transcripts. Recoated cores are virion-like particles generated by
the addition of recombinant outer capsid proteins to cores. We used recoated
cores to analyze transcriptional regulation by reovirus outer capsid proteins.
Partially recoated particles, containing less than virion amounts of mu1 and
sigma3, synthesized mRNA at levels inversely proportional to outer capsid protein
levels. Fully recoated cores exhibited undetectable mRNA synthesis levels, as did
virions. However, recoated cores produced high levels of abortive transcripts.
Recoated core abortive transcripts remained particle-associated and appeared to
inhibit further abortive transcript production. Proteolysis of recoated cores
removing mu1 and sigma3 released accumulated abortive transcripts and relieved
inhibition of mRNA and abortive transcript synthesis. These results suggest
transcriptional elongation, but not initiation, is blocked by virion-like amounts
of mu1 and sigma3. Particle-associated abortive transcripts may down-regulate
transcriptional initiation. Minor outer capsid protein sigma1 had no demonstrable
effect on transcriptional activities. Transcriptional regulation may ensure
progeny virions do not compete with transcribing particles for ribonucleoside
triphosphates.
PMID- 11007774
TI - Identification of protein-tyrosine phosphatase 1B as the major tyrosine
phosphatase activity capable of dephosphorylating and activating c-Src in several
human breast cancer cell lines.
AB - c-Src tyrosine kinase activity is elevated in several types of human cancer, and
this has been attributed to elevated c-Src expression levels, increased c-Src
specific activity, and activating mutations in c-Src. We have found a number of
human breast cancer cell lines with elevated c-Src specific activity that also
possess elevated phosphatase activity directed against the carboxyl-terminal
negative regulatory domain of Src family kinases. To identify this phosphatase,
cell extracts from MDA-MB-435S cells were chromatographed and the fractions were
assayed for phosphatase activity. Four peaks of phosphatase activity directed
against the nonspecific substrate poly(Glu/Tyr) were detected. One peak also
dephosphorylated a peptide modeled against the c-Src carboxyl-terminal negative
regulatory domain and intact human c-Src. Immunoblotting and immunodepletion
experiments identified the phosphatase as protein-tyrosine phosphatase 1B
(PTP1B). Examination of several human breast cancer cell lines with increased c
Src activity showed elevated levels of PTP1B protein relative to normal control
breast cells. In vitro c-Src reactivation experiments confirmed the ability of
PTP1B to dephosphorylate and activate c-Src. In vivo overexpression of PTP1B in
293 cells caused a 2-fold increase of endogenous c-Src kinase activity. Our
findings indicate that PTP1B is the primary protein-tyrosine phosphatase capable
of dephosphorylating c-Src in several human breast cancer cell lines and suggests
a regulatory role for PTP1B in the control of c-Src kinase activity.
PMID- 11007775
TI - TatC is a specificity determinant for protein secretion via the twin-arginine
translocation pathway.
AB - The recent discovery of a ubiquitous translocation pathway, specifically required
for proteins with a twin-arginine motif in their signal peptide, has focused
interest on its membrane-bound components, one of which is known as TatC. Unlike
most organisms of which the genome has been sequenced completely, the Gram
positive eubacterium Bacillus subtilis contains two tatC-like genes denoted tatCd
and tatCy. The corresponding TatCd and TatCy proteins have the potential to be
involved in the translocation of 27 proteins with putative twin-arginine signal
peptides of which approximately 6-14 are likely to be secreted into the growth
medium. Using a proteomic approach, we show that PhoD of B. subtilis, a
phosphodiesterase belonging to a novel protein family of which all known members
are synthesized with typical twin-arginine signal peptides, is secreted via the
twin-arginine translocation pathway. Strikingly, TatCd is of major importance for
the secretion of PhoD, whereas TatCy is not required for this process. Thus, TatC
appears to be a specificity determinant for protein secretion via the Tat
pathway. Based on our observations, we hypothesize that the TatC-determined
pathway specificity is based on specific interactions between TatC-like proteins
and other pathway components, such as TatA, of which three paralogues are present
in B. subtilis.
PMID- 11007776
TI - A single dose of methamphetamine leads to a long term reversal of the blunted
dopamine D1 receptor-mediated neocortical c-fos responses in mice deficient for
D2 and D3 receptors.
AB - Dopamine D(1) receptors play an essential role in the induction of expression of
the immediate-early gene c-fos in response to pharmacological stimuli. In the
forebrain of wild-type mice, administration of a D(1) receptor agonist leads to c
fos mRNA expression levels that are substantially higher than corresponding
levels expressed after indirect stimulation of dopamine receptors with
methamphetamine. In mice deficient for D(2) and D(3) receptors, c-fos mRNA levels
expressed in response to D(1) agonist administration are significantly blunted.
However, a single dose of methamphetamine (5 mg/kg) leads to a long lasting
reversal of the blunted c-fos responses in these mutants. In the forebrain, this
reversal is restricted to the neocortex. Moreover, methamphetamine also enhances
c-fos expression levels in preadolescent wild-type mice that normally express low
c-fos mRNA in response to D(1) agonist stimulation. Thus, a single dose of
methamphetamine leads to a long term increase in D(1) receptor-dependent c-fos
responses in brains with either low (preadolescent mice) or blunted (adult D(2)
and D(3) mutant mice) c-fos expression levels. A similar long term reversal of
the blunted c-fos responses is achieved with a single dose of a full D(1)
agonist. These results indicate that the constitutive inactivation of D(2) and
D(3) receptors leads to a decrease in agonist-promoted D(1) receptor activity
that can be reversed by intermittent agonist stimulation.
PMID- 11007777
TI - Molecular cloning, expression, functional characterization, chromosomal
localization, and gene structure of junctate, a novel integral calcium binding
protein of sarco(endo)plasmic reticulum membrane.
AB - Screening a cDNA library from human skeletal muscle and cardiac muscle with a
cDNA probe derived from junctin led to the isolation of two groups of cDNA
clones. The first group displayed a deduced amino acid sequence that is 84%
identical to that of dog heart junctin, whereas the second group had a single
open reading frame that encoded a polypeptide with a predicted mass of 33 kDa,
whose first 78 NH(2)-terminal residues are identical to junctin whereas its COOH
terminus domain is identical to aspartyl beta-hydroxylase, a member of the alpha
ketoglutarate-dependent dioxygenase family. We named the latter amino acid
sequence junctate. Northern blot analysis indicates that junctate is expressed in
a variety of human tissues including heart, pancreas, brain, lung, liver, kidney,
and skeletal muscle. Fluorescence in situ hybridization analysis revealed that
the genetic loci of junctin and junctate map to the same cytogenetic band on
human chromosome 8. Analysis of intron/exon boundaries of the genomic BAC clones
demonstrate that junctin, junctate, and aspartyl beta-hydroxylase result from
alternative splicing of the same gene. The predicted lumenal portion of junctate
is enriched in negatively charged residues and is able to bind calcium. Scatchard
analysis of equilibrium (45)Ca(2+) binding in the presence of a physiological
concentration of KCl demonstrate that junctate binds 21.0 mol of Ca(2+)/mol
protein with a k(D) of 217 +/- 20 microm (n = 5). Tagging recombinant junctate
with green fluorescent protein and expressing the chimeric polypeptide in COS-7
transfected cells indicates that junctate is located in endoplasmic reticulum
membranes and that its presence increases the peak amplitude and transient
calcium released by activation of surface membrane receptors coupled to InsP(3)
receptor activation. Our study shows that alternative splicing of the same gene
generates the following functionally distinct proteins: an enzyme (aspartyl beta
hydroxylase), a structural protein of SR (junctin), and a membrane-bound calcium
binding protein (junctate).
PMID- 11007778
TI - The enoyl-[acyl-carrier-protein] reductases FabI and FabL from Bacillus subtilis.
AB - Enoyl-[acyl-carrier-protein] (ACP) reductase is a key enzyme in type II fatty
acid synthases that catalyzes the last step in each elongation cycle. The FabI
component of Bacillus subtilis (bsFabI) was identified in the genomic data base
by homology to the Escherichia coli protein. bsFabI was cloned and purified and
exhibited properties similar to those of E. coli FabI, including a marked
preference for NADH over NADPH as a cofactor. Overexpression of the B. subtilis
fabI gene complemented the temperature-sensitive growth phenotype of an E. coli
fabI mutant. Triclosan was a slow-binding inhibitor of bsFabI and formed a stable
bsFabI.NAD(+). triclosan ternary complex. Analysis of the B. subtilis genomic
data base revealed a second open reading frame (ygaA) that was predicted to
encode a protein with a relatively low overall similarity to FabI, but contained
the Tyr-Xaa(6)-Lys enoyl-ACP reductase catalytic architecture. The purified YgaA
protein catalyzed the NADPH-dependent reduction of trans-2-enoyl thioesters of
both N-acetylcysteamine and ACP. YgaA was reversibly inhibited by triclosan, but
did not form the stable ternary complex characteristic of the FabI proteins.
Expression of YgaA complemented the fabI(ts) defect in E. coli and conferred
complete triclosan resistance. Single knockouts of the ygaA or fabI gene in B.
subtilis were viable, but double knockouts were not obtained. The fabI knockout
was as sensitive as the wild-type strain to triclosan, whereas the ygaA knockout
was 250-fold more sensitive to the drug. YgaA was renamed FabL to denote the
discovery of a new family of proteins that carry out the enoyl-ACP reductase step
in type II fatty-acid synthases.
PMID- 11007780
TI - Targeting of Rac1 to the phagocyte membrane is sufficient for the induction of
NADPH oxidase assembly.
AB - The superoxide (O(2))-generating NADPH oxidase complex of phagocytes consists of
a membrane-associated flavocytochrome (cytochrome b(559)) and four cytosolic
proteins, p47(phox), p67(phox), p40(phox), and the small GTPase Rac (Rac1 or -2).
NADPH oxidase activation (O(2) production) is elicited as the consequence of
assembly of some or all cytosolic components with cytochrome b(559). This process
can be reproduced in an in vitro system consisting of phagocyte membranes,
p47(phox), p67(phox), and Rac, activated by an anionic amphiphile. We now show
that post-translationally processed (prenylated) Rac1 initiates NADPH oxidase
assembly, expressed in O(2) production, in a cell-free system containing
phagocyte membrane vesicles and p67(phox), in the absence of an activating
amphiphile and of p47(phox). Prenylated Cdc42Hs, a GTPase closely related to Rac,
is inactive under the same conditions. Results obtained with phagocyte membrane
vesicles can be reproduced fully by replacing these with partially purified
cytochrome b(559), incorporated in phosphatidylcholine vesicles. Prenylated, but
not nonprenylated, Rac1 binds spontaneously to phagocyte membrane vesicles and
also to artificial, protein-free, phosphatidylcholine vesicles, a process
counteracted by GDP dissociation inhibitor for Rho. Binding of prenylated Rac1 to
membrane vesicles is accompanied by the recruitment of p67(phox) to the same
location and the formation of an assembled NADPH oxidase complex, producing O(2)
upon the addition of NADPH. Amphiphile and p47(phox)-independent NADPH oxidase
activation by prenylated Rac1 is inhibited by Rho GDP dissociation inhibitor and
by phosphatidylcholine vesicles, both competing with membrane for prenylated
Rac1. We conclude that, in vitro, targeting of Rac to the phagocyte membrane is
sufficient for the induction of NADPH oxidase assembly, suggesting that the
principal or, possibly, the only role of Rac is to recruit cytosolic p67(phox) to
the membrane environment, to be followed by the interaction of p67(phox) with
cytochrome b(559).
PMID- 11007779
TI - Calmodulin differentially modulates Smad1 and Smad2 signaling.
AB - The members of the Smad protein family are intracellular mediators of
transforming growth factor beta (TGF-beta) signaling. Smad1 transduces bone
morphogenetic protein signals, inducing formation of ventral mesoderm in Xenopus
embryos, whereas Smad2 transduces activin/TGF-beta signals, generating dorsal
mesoderm. Calmodulin directly binds to many Smads and was shown to down-regulate
Smad2 activity in a cell culture system (Zimmerman, C. M., Kariapper, M. S. T.,
and Mathews, L. S. (1997) J. Biol. Chem. 273, 677-680). Here, we extend those
data and demonstrate that calmodulin alters Smad signaling in living embryos,
increasing Smad1 activity while inhibiting Smad2 function. To characterize this
regulation, we undertook a structure-function analysis and found that calmodulin
binds to two distinct and conserved regions in both Smad1 and Smad2. Receptor
tyrosine kinase signaling also modifies Smad activity (Kretzschmar, M., Doody,
J., and Massague, J. (1997) Nature 389, 618-622; Kretzschmar, M., Doody, J.,
Timokhina, I., and Massague, J. (1999) Genes Dev. 13, 804-816; de Caestecker, M.
P., Parks, W. T., Frank, C. J., Castagnino, P., Bottaro, D. P., Roberts, A. B.,
and Lechleider, R. J. (1998) Genes Dev. 12, 1587-1592). We show that calmodulin
binding to Smads inhibits subsequent Erk2-dependent phosphorylation of Smads and
vice versa. These observations suggest the presence of a cross-talk between three
major signaling cascades as follows: Ca(2+)/calmodulin, receptor tyrosine kinase,
and TGF-beta pathways.
PMID- 11007781
TI - Radicicol binds and inhibits mammalian ATP citrate lyase.
AB - Six different biotinylated radicicol derivatives were synthesized as affinity
probes for identification of cellular radicicol-binding proteins. Derivatives
biotinylated at the C-17 (BR-1) and C-11 (BR-6) positions retained the activity
of morphological reversion in v-src-transformed 3Y1 fibroblasts. Two radicicol
binding proteins, 120 and 90-kDa in size, were detected in HeLa cell extracts by
employing BR-1 and BR-6, respectively. The 90-kDa protein bound to BR-6 was
identified to be Hsp90 by immunoblotting. The 120-kDa protein bound to BR-1 was
purified from rabbit reticulocyte lysate, and its internal amino acid sequence
was identical to that of human and rat ATP citrate lyase. The identity of the 120
kDa protein as ATP citrate lyase was confirmed by immunoblotting. Interaction
between BR-1 and ATP citrate lyase was blocked by radicicol but not by herbimycin
A that interacts with Hsp90. These results suggest that radicicol binds the two
proteins through different molecular portions of its structure. BR-1-bound ATP
citrate lyase isolated from rabbit reticulocyte lysate showed no enzymatic
activity. The activity of rat liver ATP citrate lyase was inhibited by radicicol
and BR-1 but not by BR-6. Kinetic analysis demonstrated that radicicol was a non
competitive inhibitor of ATP citrate lyase with K(i) values for citrate and ATP
of 13 and 7 microm, respectively.
PMID- 11007782
TI - Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the
axonopathy in the central nervous system of human four-repeat tau transgenic
mice.
AB - Protein tau filaments in brain of patients suffering from Alzheimer's disease,
frontotemporal dementia, and other tauopathies consist of protein tau that is
hyperphosphorylated. The responsible kinases operating in vivo in neurons still
need to be identified. Here we demonstrate that glycogen synthase kinase-3beta
(GSK-3beta) is an effective kinase for protein tau in cerebral neurons in vivo in
adult GSK-3beta and GSK-3beta x human tau40 transgenic mice. Phosphorylated
protein tau migrates slower during electrophoretic separation and is revealed by
phosphorylation-dependent anti-tau antibodies in Western blot analysis. In
addition, its capacity to bind to re-assembled paclitaxel (Taxol((R)))-stabilized
microtubules is reduced, compared with protein tau isolated from mice not
overexpressing GSK-3beta. Co-expression of GSK-3beta reduces the number of axonal
dilations and alleviates the motoric impairment that was typical for single
htau40 transgenic animals (Spittaels, K., Van den Haute, C., Van Dorpe, J.,
Bruynseels, K., Vandezande, K., Laenen, I., Geerts, H., Mercken, M., Sciot, R.,
Van Lommel, A., Loos, R., and Van Leuven, F. (1999) Am. J. Pathol. 155, 2153
2165). Although more hyperphosphorylated protein tau is available, neither an
increase in insoluble protein tau aggregates nor the presence of paired helical
filaments or tangles was observed. These findings could have therapeutic
implications in the field of neurodegeneration, as discussed.
PMID- 11007783
TI - Singlet oxygen induces oxidation of cellular DNA.
AB - The aim of the present work was to evaluate the potential for (1)O(2) to induce
oxidation of cellular DNA. For this purpose cells were incubated in the presence
of a water-soluble endoperoxide whose thermal decomposition leads to the
formation of singlet oxygen. Thereafter, DNA was extracted and the level of
several modified DNA bases was determined by HPLC analysis coupled to a tandem
mass spectrometric detection. A significant increase in the level of 8-oxo-7,8
dihydro-2'-deoxyguanosine was observed upon incubation of the cells with the
chemical generator of (1)O(2), whereas the level of the other DNA bases measured
remained unchanged. To demonstrate that singlet oxygen is directly involved in
the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine, the corresponding (18)O
labeled endoperoxide was used. Incubation of the cells with such a generator of
(18)O-labeled singlet oxygen results in the formation of (18)O-labeled 8-oxo-7,8
dihydro-2'-deoxyguanosine in the nuclear DNA. This result clearly demonstrates
that singlet oxygen, when released within cells, is able to directly oxidize
cellular DNA.
PMID- 11007785
TI - The C-terminal polylysine region and methylation of K-Ras are critical for the
interaction between K-Ras and microtubules.
AB - After synthesis in the cytosol, Ras proteins must be targeted to the inner
leaflet of the plasma membrane for biological activity. This targeting requires a
series of C-terminal posttranslational modifications initiated by the addition of
an isoprenoid lipid in a process termed prenylation. A search for factors
involved in the intracellular trafficking of Ras has identified a specific and
prenylation-dependent interaction between tubulin/microtubules and K-Ras. In this
study, we examined the structural requirements for this interaction between K-Ras
and microtubules. By using a series of chimeras in which regions of the C
terminus of K-Ras were replaced with those of Ha-Ras and vice versa, we found
that the polylysine region of K-Ras located immediately upstream of the
prenylation site is required for binding of K-Ras to microtubules. Studies in
intact cells confirmed the importance of the K-Ras polylysine region for
microtubule binding, as deletion or replacement of this region resulted in loss
of paclitaxel-induced mislocalization of a fluorescent K-Ras fusion protein. The
additional modifications in the prenyl protein processing pathway also affected
the interaction of K-Ras with microtubules. Removal of the three C-terminal amino
acids of farnesylated K-Ras with the specific endoprotease Rce1p abolished its
binding to microtubules. Interestingly, however, methylation of the C-terminal
prenylcysteine restored binding. Consistent with these results, localization of
the fluorescent K-Ras fusion protein remained paclitaxel-sensitive in cells
lacking Rce1, whereas no paclitaxel effect was observed in cells lacking the
methyltransferase. These studies show that the polylysine region of K-Ras is
critical for its interaction with microtubules and provide the first evidence for
a functional consequence of Ras C-terminal proteolysis and methylation.
PMID- 11007784
TI - Ras inactivation of the retinoblastoma pathway by distinct mechanisms in NIH 3T3
fibroblast and RIE-1 epithelial cells.
AB - Although Ras and Raf cause transformation of NIH 3T3 fibroblasts, only Ras causes
transformation of RIE-1 intestinal epithelial cells. To determine if the
inability of Raf to transform RIE-1 cells is due to a failure to deregulate cell
cycle progression, we evaluated the consequences of sustained Ras and Raf
activation on steady state levels of cyclin D1, p21(CIP/WAF), and p27(KIP1). Both
Ras- and Raf-transformed NIH 3T3 cells showed up-regulated expression of cyclin
D1, p21, and p27 protein, increased retinoblastoma (Rb) hyperphosphorylation, and
increased activation of E2F-mediated transcription. Similarly, Ras-transformed
RIE-1 cells also showed up-regulation of cyclin D1, p21, and hyperphosphorylated
Rb. In contrast, Ras-mediated down-regulation of p27 was seen in RIE-1 cells.
Conversely, stable expression of activated Raf alone caused only a partial up
regulation of p21 and Rb hyperphosphorylation but no activation of E2F-responsive
transcription or down-regulation of p27 in RIE-1 cells. Moreover, we found that
the AP-1 site was dispensable for Ras-mediated stimulation of the cyclin-D1
promoter in NIH 3T3 cells but was essential for Ras-mediated stimulation in RIE-1
cells. Thus, up-regulation of p21, rather than the down-regulation seen in
previous transient expression studies, is seen with sustained Ras activation.
Additionally, p27 may serve a positive (NIH 3T3) or negative (RIE-1) regulatory
role in Ras transformation that is cell type-dependent. The involvement of Raf
and phosphatidylinositol 3-kinase in mediating Ras changes in cyclin D1, p21, and
p27 was also very distinct in NIH 3T3 and RIE-1 cells. Taken together, these
results demonstrate the importance of Raf-independent pathways in mediating
oncogenic Ras deregulation of cell cycle progression in epithelial cells.
PMID- 11007786
TI - Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is
the lung scavenger receptor cysteine-rich protein gp-340.
AB - Salivary agglutinin is a high molecular mass component of human saliva that binds
Streptococcus mutans, an oral bacterium implicated in dental caries. To study its
protein sequence, we isolated the agglutinin from human parotid saliva. After
trypsin digestion, a portion was analyzed by matrix-assisted laser/desorption
ionization time-of-flight mass spectrometry (MALDI-TOF MS), which gave the
molecular mass of 14 unique peptides. The remainder of the digest was subjected
to high performance liquid chromatography, and the separated peptides were
analyzed by MALDI-TOF/post-source decay; the spectra gave the sequences of five
peptides. The molecular mass and peptide sequence information showed that
salivary agglutinin peptides were identical to sequences in lung (lavage) gp-340,
a member of the scavenger receptor cysteine-rich protein family. Immunoblotting
with antibodies that specifically recognized either lung gp-340 or the agglutinin
confirmed that the salivary agglutinin was gp-340. Immunoblotting with an
antibody specific to the sialyl Le(x) carbohydrate epitope detected expression on
the salivary but not the lung glycoprotein, possible evidence of different
glycoforms. The salivary agglutinin also interacted with Helicobacter pylori,
implicated in gastritis and peptic ulcer disease, Streptococcus agalactiae,
implicated in neonatal meningitis, and several oral commensal streptococci. These
results identify the salivary agglutinin as gp-340 and suggest it binds bacteria
that are important determinants of either the oral ecology or systemic diseases.
PMID- 11007787
TI - Coregulation of neurite outgrowth and cell survival by amphoterin and S100
proteins through receptor for advanced glycation end products (RAGE) activation.
AB - Amphoterin is a protein enhancing process extension and migration in embryonic
neurons and in tumor cells through binding to receptor for advanced glycation end
products (RAGE), a multiligand transmembrane receptor. S100 proteins, especially
S100B, are abundantly expressed in the nervous system and are suggested to
function as cytokines with both neurotrophic and neurotoxic effects. However, the
cell surface receptor for the cytokine function of S100B has not been identified.
Here we show that two S100 family proteins, S100B and S100A1, activate RAGE in
concert with amphoterin inducing neurite outgrowth and activation of
transcription factor NF-kappaB. Furthermore, activation of RAGE by amphoterin and
S100B promotes cell survival through increased expression of the anti-apoptotic
protein Bcl-2. However, whereas nanomolar concentrations of S100B induce trophic
effects in RAGE-expressing cells, micromolar concentrations of S100B induce
apoptosis in an oxidant-dependent manner. Both trophic and toxic effects are
specific for cells expressing full-length RAGE since cells expressing a
cytoplasmic domain deletion mutant of RAGE are unresponsive to these stimuli.
These findings suggest that activation of RAGE by multiple ligands is able to
promote trophic effects whereas hyperactivation of RAGE signaling pathways
promotes apoptosis. We suggest that RAGE is a signal-transducing receptor for
both trophic and toxic effects of S100B.
PMID- 11007788
TI - Altered distribution of the yeast plasma membrane H+-ATPase as a feature of
vacuolar H+-ATPase null mutants.
AB - The effect of vacuolar H(+)-ATPase (V-ATPase) null mutations on the targeting of
the plasma membrane H(+)-ATPase (Pma1p) through the secretory pathway was
analyzed. Gas1p, which is another plasma membrane component, was used as a
control for the experiments with Pma1p. Contrary to Gas1p, which is not affected
by the deletion of the V-ATPase complex in the V-ATPase null mutants, the amount
of Pma1p in the plasma membrane is markedly reduced, and there is a large
accumulation of the protein in the endoplasmic reticulum. Kex2p and Gef1p, which
are considered to reside in the post-Golgi vesicles, were suggested as required
for the V-ATPase function; hence, their null mutant phenotype should have been
similar to the V-ATPase null mutants. We show that, in addition to the known
differences between those yeast phenotypes, deletions of KEX2 or GEF1 in yeast do
not affect the distribution of Pma1p as the V-ATPase null mutant does. The
possible location of the vital site of acidification by V-ATPase along the
secretory pathway is discussed.
PMID- 11007789
TI - The enigma of cobalamin (Vitamin B12) biosynthesis in Porphyromonas gingivalis.
Identification and characterization of a functional corrin pathway.
AB - The ability of Porphyromonas gingivalis to biosynthesize tetrapyrroles de novo
has been investigated. Extracts of the bacterium do not possess activity for 5-
aminolevulinic-acid dehydratase or porphobilinogen deaminase, two key enzymes
involved in the synthesis of uroporphyrinogen III. Similarly, it was not possible
to detect any genetic evidence for these early enzymes with the use of degenerate
polymerase chain reaction. However, the bacterium does appear to harbor some of
the enzymes for cobalamin biosynthesis since cobyric acid, a pathway
intermediate, was converted into cobinamide. Furthermore, degenerate polymerase
chain reaction with primers to cbiP, which encodes cobyric-acid synthase,
produced a fragment with a high degree of identity to Salmonella typhimurium
cbiP. Indeed, the recently released genome sequence data confirmed the presence
of cbiP together with 14 other genes of the cobalamin pathway. A number of these
genes were cloned and functionally characterized. Although P. gingivalis harbors
all the genes necessary to convert precorrin-2 into cobalamin, it is missing the
genes for the synthesis of precorrin-2. Either the organism has a novel pathway
for the synthesis of precorrin-2, or more likely, it has lost this early part of
the pathway. The remainder of the pathway may be being maintained to act as a
salvage route for corrin synthesis.
PMID- 11007790
TI - High glucose inhibits glucose-6-phosphate dehydrogenase via cAMP in aortic
endothelial cells.
AB - Recent studies have shown that hyperglycemia is a principal cause of cellular
damage in patients with diabetes mellitus. A major consequence of hyperglycemia
is increased oxidative stress. Glucose-6-phosphate dehydrogenase (G6PD) plays an
essential role in the regulation of oxidative stress by primarily regulating
NADPH, the main intracellular reductant. In this paper we show that increased
glucose (10-25 mm) caused inhibition of G6PD resulting in decreased NADPH levels
in bovine aortic endothelial cells (BAEC). Inhibition was seen within 15 min.
High glucose-induced inhibition of G6PD predisposed cells to cell death. High
glucose via increased activity of adenylate cyclase also stimulated an increase
in cAMP levels in BAEC. Agents that increased cAMP caused a decrease in G6PD
activity. Inhibition of cAMP-dependent protein kinase A ameliorated the high
glucose-induced inhibition of G6PD. Finally, high glucose stimulated
phosphorylation of G6PD. These results suggest that, in BAEC, high glucose
stimulated increased cAMP, which led to increased protein kinase A activity,
phosphorylation of G6PD, and inhibition of G6PD activity. We conclude that these
changes in G6PD activity play an important role in high glucose-induced cell
damage/death.
PMID- 11007791
TI - The crystal structure of 3alpha -hydroxysteroid dehydrogenase/carbonyl reductase
from Comamonas testosteroni shows a novel oligomerization pattern within the
short chain dehydrogenase/reductase family.
AB - The crystal structure of 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase
from Comamonas testosteroni (3alpha-HSDH) as well as the structure of its binary
complex with NAD(+) have been solved at 1.68-A and 1.95-A resolution,
respectively. The enzyme is a member of the short chain dehydrogenase/reductase
(SDR) family. Accordingly, the active center and the conformation of the bound
nucleotide cofactor closely resemble those of other SDRs. The crystal structure
reveals one homodimer per asymmetric unit representing the physiologically active
unity. Dimerization takes place via an interface essentially built-up by helix
alphaG and strand betaG of each subunit. So far this type of intermolecular
contact has exclusively been observed in homotetrameric SDRs but never in the
structure of a homodimeric SDR. The formation of a tetramer is blocked in 3alpha
HSDH by the presence of a predominantly alpha-helical subdomain which is missing
in all other SDRs of known structure.
PMID- 11007792
TI - Detection of large pKa perturbations of an inhibitor and a catalytic group at an
enzyme active site, a mechanistic basis for catalytic power of many enzymes.
AB - Delta(5)-3-Ketosteroid isomerase catalyzes cleavage and formation of a C-H bond
at a diffusion-controlled limit. By determining the crystal structures of the
enzyme in complex with each of three different inhibitors and by nuclear magnetic
resonance (NMR) spectroscopic investigation, we evidenced the ionization of a
hydroxyl group (pK(a) approximately 16.5) of an inhibitor, which forms a low
barrier hydrogen bond (LBHB) with a catalytic residue Tyr(14) (pK(a)
approximately 11.5), and the protonation of the catalytic residue Asp(38) with
pK(a) of approximately 4.5 at pH 6.7 in the interaction with a carboxylate group
of an inhibitor. The perturbation of the pK(a) values in both cases arises from
the formation of favorable interactions between inhibitors and catalytic
residues. The results indicate that the pK(a) difference between catalytic
residue and substrate can be significantly reduced in the active site environment
as a result of the formation of energetically favorable interactions during the
course of enzyme reactions. The reduction in the pK(a) difference should
facilitate the abstraction of a proton and thereby eliminate a large fraction of
activation energy in general acid/base enzyme reactions. The pK(a) perturbation
provides a mechanistic ground for the fast reactivity of many enzymes and for the
understanding of how some enzymes are able to extract a proton from a C-H group
with a pK(a) value as high as approximately 30.
PMID- 11007793
TI - Characterization of variants altered at the N-terminal proline, a novel heme
axial ligand in CooA, the CO-sensing transcriptional activator.
AB - CooA, the carbon monoxide-sensing transcription factor from Rhodospirillum
rubrum, binds CO through a heme moiety resulting in conformational changes that
promote DNA binding. The crystal structure shows that the N-terminal Pro(2) of
one subunit (Met(1) is removed post-translationally) provides one ligand to the
heme of the other subunit in the CooA homodimer. To determine the importance of
this novel ligand and the contiguous residues to CooA function, we have altered
the N terminus through two approaches: site-directed mutagenesis and regional
randomization, and characterized the resulting CooA variants. While Pro(2)
appears to be optimal for CooA function, it is not essential and a variety of
studied variants at this position have substantial CO-sensing function.
Surprisingly, even alterations that add a residue (where Pro(2) is replaced by
Met(1)-Tyr(2), for example) accumulate heme-containing CooA with functional
properties that are similar to those of wild-type CooA. Other nearby residues,
such as Phe(5) and Asn(6) appear to be important for either the structural
integrity or the function of CooA. These results are contrasted with those
previously reported for alteration of the His(77) ligand on the opposite side of
the heme.
PMID- 11007794
TI - Interaction between 4-hydroxy-2,3-alkenals and the platelet-derived growth factor
beta receptor. Reduced tyrosine phosphorylation and downstream signaling in
hepatic stellate cells.
AB - Hepatic stellate cells (HSC) undergo activation toward myofibroblast-like cells
during early stages of liver injury associated with fibrogenesis. Platelet
derived growth factor (PDGF), particularly its BB isoform, has been identified as
the most potent mitogen for HSC. 4-Hydroxy-2,3-nonenal and related 4-hydroxy-2, 3
alkenals (HAKs) have been suggested to modulate the process of HSC activation. In
this study we investigated the relationship between HAKs and PDGF receptor
activation in human HSC. By employing noncytotoxic concentrations (10(-6) m) of
HAKs, we observed a significant inhibition of PDGF-BB-dependent DNA synthesis.
HAKs inhibited relevant pathways of PDGF-BB-dependent mitogenic signaling,
including autophosphorylation of PDGF receptor (PDGF-R) beta subunits and
activation of phosphatidylinositol 3-kinase and extracellular regulated kinases
1/2. Inhibition of DNA synthesis was reversible, and recovery of PDGF-mediated
mitogenic signaling occurred within 24-48 h and was associated with HAKs-induced
up-regulation of PDGF-R beta gene expression. 4-Hydroxy-2,3-nonenal, used as a
model HAK, inhibited the intrinsic tyrosine kinase activity associated with the
PDGF-R beta subunit, whereas binding of PDGF to its receptor was unaffected. This
study identifies a novel regulatory mechanism of reactive aldehydes on PDGF
receptor signaling and biologic actions, which may be relevant in several
pathophysiological conditions, including liver fibrosis.
PMID- 11007795
TI - The amino-terminal part of PRELP binds to heparin and heparan sulfate.
AB - PRELP (proline, arginine-rich end leucine-rich repeat protein) is an
extracellular matrix leucine-rich repeat protein. The amino-terminal region of
PRELP differs from that of other leucine-rich repeat proteins in containing a
high number of proline and arginine residues. The clustered proline and basic
residues are conserved in rat, bovine, and human PRELP. Although the function of
PRELP is not yet known, the clustered arginine residues suggest a heparan
sulfate/heparin-binding capacity. We show here that PRELP indeed binds heparin
and heparan sulfate. Truncated PRELP without the amino-terminal region does not
bind heparin. The dissociation constant for the interaction of PRELP with heparin
was determined by an in solution binding assay and by surface plasmon resonance
analysis to be in the range of 10-30 nm. A 6-mer heparin oligosaccharide was the
smallest size showing binding to PRELP. The binding increased with increasing
length up to an 18-mer and depended on the degree of sulfation of heparin as well
as heparan sulfate. Sulfate groups at all positions were shown to be of
importance for the binding. Fibroblasts bind PRELP, and this interaction is
inhibited with heparin, suggesting a function for PRELP as a linker between the
matrix and cell surface proteoglycans.
PMID- 11007796
TI - Glucose activates mitogen-activated protein kinase (extracellular signal
regulated kinase) through proline-rich tyrosine kinase-2 and the Glut1 glucose
transporter.
AB - Glucose serves as both a nutrient and regulator of physiological and pathological
processes. Presently, we found that glucose and certain sugars rapidly activated
extracellular signal-regulated kinase (ERK) by a mechanism that was: (a)
independent of glucose uptake/metabolism and protein kinase C but nevertheless
cytochalasin B-inhibitable; (b) dependent upon proline-rich tyrosine kinase-2
(PYK2), GRB2, SOS, RAS, RAF, and MEK1; and (c) amplified by overexpression of the
Glut1, but not Glut2, Glut3, or Glut4, glucose transporter. This amplifying
effect was independent of glucose uptake but dependent on residues 463-468,
IASGFR, in the Glut1 C terminus. Accordingly, glucose effects on ERK were
amplified by expression of Glut4/Glut1 or Glut2/Glut1 chimeras containing IASGFR
but not by Glut1/Glut4 or Glut1/Glut2 chimeras lacking these residues. Also,
deletion of Glut1 residues 469-492 was without effect, but mutations involving
serine 465 or arginine 468 yielded dominant-negative forms that inhibited glucose
dependent ERK activation. Glucose stimulated the phosphorylation of tyrosine
residues 402 and 881 in PYK2 and binding of PYK2 to Myc-Glut1. Our findings
suggest that: (a) glucose activates the GRB2/SOS/RAS/RAF/MEK1/ERK pathway by a
mechanism that requires PYK2 and residues 463-468, IASGFR, in the Glut1 C
terminus and (b) Glut1 serves as a sensor, transducer, and amplifier for glucose
signaling to PYK2 and ERK.
PMID- 11007797
TI - The acceptor and site specificity of alpha 3-fucosyltransferase V. High
reactivity of the proximal and low of the distal galbeta 1-4GlcNAc unit in i-type
polylactosamines.
AB - We report here on in vitro acceptor and site specificity of recombinant alpha3
fucosyltransferase V (Fuc-TV) with 40 oligosaccharide acceptors. Galbeta1-4GlcNAc
(LN) and GalNAcbeta1-4GlcNAc (LDN) reacted rapidly; Galbeta1-3GlcNAc (LNB)
reacted moderately, and GlcNAcbeta1-4GlcNAc (N, N'-diacetyl-chitobiose) reacted
slowly yet distinctly. In neutral and terminally alpha3-sialylated
polylactosamines of i-type, the reducing end LN unit reacted rapidly and the
distal (sialyl)LN group very slowly; the midchain LNs revealed intermediate
reactivities. The data suggest that a distal LN neighbor enhances but a proximal
LN neighbor reduces the reactivity of the midchain LNs. This implies that Fuc-TV
may bind preferably the tetrasaccharide sequence Galbeta1-4GlcNAcbeta1-3Galbeta1
4GlcNAc for transfer at the underlined monosaccharide. Terminal alpha3
sialylation of i-type polylactosamines almost doubled the reactivities of the LN
units at all positions of the chains. We conclude that, in comparison with human
Fuc-TIV and Fuc-TIX, Fuc-TV reacted with a highly distinct site specificity with
i-type polylactosamines. The Fuc-TV reactivity of free LNB resembled that of
LNBbeta1-3'R of a polylactosamine, contrasting strongly with the dissimilarity of
the reactivities of the analogous pair of LN and LNbeta1-3'R. This observation
supports the notion that LN and LNB may be functionally bound at distinct sites
on Fuc-TV surface. Our data show that Fuc-TV worked well with a very wide range
of LN-glycans, showing weak reactivity only with distal (sialyl)LN units of i
type polylactosamines, biantennary N-glycans, and I branches of polylactosamines.
PMID- 11007798
TI - Localization of the death domain of tissue inhibitor of metalloproteinase-3 to
the N terminus. Metalloproteinase inhibition is associated with proapoptotic
activity.
AB - The tissue inhibitors of metalloproteinases (TIMPs) are a family of four secreted
inhibitors of matrix metalloproteinases (MMPs). Recently, additional functions
have been attributed to the TIMPs, including cell growth and inhibition of
angiogenesis. In particular, we demonstrated that TIMP-3 overexpression using
gene transfer induces apoptosis in a variety of cell types and can inhibit
vascular neointima formation in vivo. However, little is know about the
mechanisms underlying TIMP-3-mediated apoptosis. Here, using both purified
recombinant proteins and novel adenoviral vectors we demonstrate that the
prodeath domain of TIMP-3 is located within the N-terminal three loops of TIMP-3.
Although both wild type and N-terminal TIMP-3 proteins promoted apoptosis, a T
2/T-3 chimera, in which the N-terminal three loops of TIMP-3 are replaced by
those of TIMP-2, failed to induce cell death. Furthermore, a point mutation at
residue 1 of TIMP-3 totally abolished MMP-inhibitory activity of TIMP-3 and also
failed to promote apoptosis. This study demonstrates, using multiple apoptosis
assays, that the prodeath function of TIMP-3 is located within the N-terminal
three loops and the presence of functional metalloproteinase-inhibitory activity
is associated with the induction of apoptosis.
PMID- 11007799
TI - cDNA cloning and expression of a human aldehyde dehydrogenase (ALDH) active with
9-cis-retinal and identification of a rat ortholog, ALDH12.
AB - This report describes the isolation of a heretofore uncharacterized aldehyde
dehydrogenase (ALDH) with retinal dehydrogenase activity from rat kidney and the
cloning and expression of a cDNA that encodes its human ortholog, the previously
unknown ALDH12. The human ALDH12 cDNA predicts a 487-residue protein with the 23
invariant amino acids, four conserved regions, cofactor binding motif
(G(209)XGX(3)G), and active site cysteine residue (Cys(287)) that typify members
of the ALDH superfamily. ALDH12 seems at least as efficient (V(m)/K(m)) in
converting 9-cis-retinal into the retinoid X receptor ligand 9-cis-retinoic acid
as two previously identified ALDHs with 9-cis-retinal dehydrogenase activity, rat
retinal dehydrogenase (RALDH) 1 and RALDH2. ALDH12, however, has approximately 40
fold higher activity with 9-cis- retinal than with all-trans-retinal, whereas
RALDH1 and RALDH2 have equivalent and approximately 4-fold less efficiencies for
9-cis-retinal versus all-trans-retinal, respectively. Therefore, ALDH12 is the
first known ALDH to show a preference for 9-cis-retinal relative to all-trans
retinal. Evidence consistent with the possibility that ALDH12 could function in a
pathway of 9-cis-retinoic acid biosynthesis in vivo includes biosynthesis of 9
cis-retinoic acid from 9-cis-retinol in cells co-transfected with cDNAs encoding
ALDH12 and the 9-cis-retinol/androgen dehydrogenase, cis-retinoid/androgen
dehydrogenase type 1. Intense ALDH12 mRNA expression in adult and fetal liver and
kidney, two organs that reportedly have relatively high concentrations of 9-cis
retinol, reinforces this notion.
PMID- 11007800
TI - p53 amino acids 339-346 represent the minimal p53 repression domain.
AB - The p53 tumor suppressor protein functions as an activator and also as a
repressor of gene transcription. Currently, the mechanism of transcriptional
repression by p53 remains poorly understood. To help clarify this mechanism, we
carried out studies designed to identify the minimal repression domain that
inhibits p53 transcriptional activities. We found only eight amino acids (339) of
the COOH-terminal domain (termed P53MRD) that possess activities of repression.
The exact location of this minimal domain is on the E6-binding region, and it
lacks the ability of tetramerization. P53MRD is able to repress the transcription
of p53 while not affecting VP16. The mutants (amino acids M340P and F341D) of
native p53 also lost transcriptional repression of the thymidine kinase
chloramphenicol acetyltransferase promoter. These results suggest that this eight
amino acid element is required for the repression of p53.
PMID- 11007801
TI - Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent
death effector domain.
AB - Huntington disease is a devastating neurodegenerative disease caused by the
expansion of a polymorphic glutamine tract in huntingtin. The huntingtin
interacting protein (HIP-1) was identified by its altered interaction with mutant
huntingtin. However, the function of HIP-1 was not known. In this study, we
identify HIP-1 as a proapoptotic protein. Overexpression of HIP-1 resulted in
rapid caspase 3-dependent cell death. Bioinformatics analyses identified a novel
domain in HIP-1 with homology to death effector domains (DEDs) present in
proteins involved in apoptosis. Expression of the HIP-1 DED alone resulted in
cell death indistinguishable from HIP-1, indicating that the DED is responsible
for HIP-1 toxicity. Furthermore, substitution of a conserved hydrophobic
phenylalanine residue within the HIP-1 DED at position 398 eliminated HIP-1
toxicity entirely. HIP-1 activity was found to be independent of the DED
containing caspase 8 but was significantly inhibited by the antiapoptotic protein
Bcl-x(L), implicating the intrinsic pathway of apoptosis in HIP-1-induced cell
death. Co-expression of a normal huntingtin fragment capable of binding HIP-1
significantly reduced cell death. Our data identify HIP-1 as a novel proapoptotic
mediator and suggest that HIP-1 may be a molecular accomplice in the pathogenesis
of Huntington disease.
PMID- 11007803
TI - Journal of pediatric psychology: A brief history (1969-1999)
PMID- 11007802
TI - Glucose residues as key determinants in the biosynthesis and quality control of
glycoproteins with N-linked oligosaccharides.
PMID- 11007804
TI - Family rituals as a protective factor for children with asthma.
AB - OBJECTIVE: To examine how one aspect of family life, notably family rituals and
routines, may protect children with asthma from anxiety-related symptoms.
METHODS: Eighty-six families (43 children with asthma, 43 healthy comparison
children) participated in the study. Children completed measures of anxiety
(Revised Child Manifest Anxiety Scale) and health. Parents completed measures of
stress (Parenting Stress Index), family rituals (Family Routines Questionnaire),
and family health. RESULTS: Families that reported more meaning in their family
routines had children who reported lower levels of anxiety. Mother endorsement of
family ritual meaning and father endorsement of family ritual routine were most
strongly related to lower levels of anxiety. Support for the protective function
of meaningful family rituals was stronger when a general health stress model was
used rather than the presence or absence of asthma alone. CONCLUSIONS: Family
rituals may serve a protective function for children with asthma under conditions
of heightened parenting stress.
PMID- 11007805
TI - The influence of parent-child relatedness on depressive symptoms in children with
asthma: tests of moderator and mediator models.
AB - OBJECTIVE: To examine the influence of parent-child relationship quality on the
association between illness-related functional status and depressive symptoms in
children with asthma. METHODS: Questionnaire data were collected from the child,
caregiver, and physician. Fifty-five children with asthma (8-17 years of age),
their caregivers, and physicians participated. RESULTS: Regression analyses
suggest that patterns of mother-child relatedness (secure vs. insecure) mediate
the relationship between functional status and depressive symptoms. CONCLUSIONS:
The parent-child relationship may be an important pathway by which illness
influences symptoms of depression in children with asthma. This study suggests
that impaired functional status does not directly contribute to symptoms of
depression, but rather influences the parent-child relationship in ways that may
promote the development of depressive symptoms in the child.
PMID- 11007806
TI - Aggression, antisocial behavior, and substance abuse in survivors of pediatric
cancer: possible protective effects of cancer and its treatment.
AB - OBJECTIVE: To examine aggression, antisocial behavior, and substance abuse in
young adult survivors of pediatric cancer (PCS) relative to case control peers
(CC). METHODS: We obtained self-reports of current aggression, antisocial
behavior, and lifetime substance use from 26 PCS (time off-treatment, M: = 56
months) and 26 CC using the Antisocial Behavior Checklist and the Drinking and
Drug History. A report of current aggression and antisocial behavior also was
obtained from primary caregivers using the Child Behavior Checklist. RESULTS: PCS
self-reported significantly less illegal drug use and experimentation than CC. No
significant differences emerged between groups for use of alcohol and tobacco nor
for aggression and antisocial behavior. CONCLUSIONS: PCS are functioning as well
as, or better than, CC in terms of aggression, antisocial behavior, and substance
abuse. However, given the compromised health status of survivors, efforts should
focus on further reduction of drug-related risk behaviors that may amplify organ
damage or increase risk for further malignancies in this population.
PMID- 11007807
TI - Neurocognitive functioning and magnetic resonance imaging in children with sickle
cell disease.
AB - OBJECTIVE: To examine neurocognitive functioning in children classified with
overt cerebral vascular accidents (CVAs), silent infarcts, or without central
nervous system (CNS) pathology on magnetic resonance imaging. METHODS:
Participants were 63 children and adolescents with sickle cell disease (SCD).
RESULTS: Children with overt CVAs and silent infarcts differed from their peers
without CNS pathology on measures of attention and executive functioning.
CONCLUSIONS: We consider these deficits the result of the high frequency of
frontal lobe deficits incurred by children with SCD. Recommendations include the
use of tests designed to measure attention and executive functioning as a way of
screening children with SCD for possible CNS pathology. We also suggest that
future research examine the mechanism underlying frontal lobe involvement for
individuals with SCD.
PMID- 11007808
TI - Brief report: speed of information processing in children with insulin-dependent
diabetes mellitus.
AB - OBJECTIVE: To determine whether children with insulin-dependent diabetes mellitus
(IDDM) process information more slowly than children who do not have diabetes.
METHODS: We tested 31 children with early onset and longer duration of IDDM, 35
with later onset and briefer duration of IDDM, and 36 comparison children without
diabetes. They were administered five tasks requiring rapid responding that
assessed a range of cognitive processes. RESULTS: On most tasks, children in the
three groups were quite similar in the accuracy and speed of performance.
Furthermore, for children in the diabetic groups, disease-related variables were
unrelated to accuracy and speed of performance. CONCLUSIONS: The results suggest
that children with IDDM do not have a pervasive deficit in speed of information
processing, although more circumscribed deficits in processing speed are
possible.
PMID- 11007809
TI - Pioneers in pediatric psychology: a career in pediatric psychology.
PMID- 11007810
TI - Microvascular disease--the Cinderella of uraemic heart disease.
AB - It has been known for a long time that atherosclerosis, particularly plaques in
the epicardiac coronary conduit arteries, are more frequent in patients with
chronic renal failure than in non-uraemic patients. It has been only recently,
however, that modification of post-stenotic remodelling of cardiac arteries as
well as abnormalities of the arterioles and the capillaries in the myocardium of
uraemic animals and uraemic patients have been recognized and analysed. These
lesions can be dissociated from changes in blood pressure and may be an important
cause contributing to reduced ischaemia tolerance and cardiac malfunction (pump
failure, arrhythmia) thus predisposing to cardiac death. Recent insights into
angiogenesis, particularly adaptive angiogenesis in response to hypoxia, may
potentially provide novel approaches to the understanding and management of
cardiac microangiopathy in renal failure.
PMID- 11007811
TI - Macula densa signalling--a potential role of cyclooxygenase-2 (COX-2)?
PMID- 11007812
TI - Is there a role for locally produced complement in renal disease?
PMID- 11007813
TI - Smoking and the kidney.
PMID- 11007814
TI - Pastis and hypertension--what is the molecular basis?
PMID- 11007815
TI - Hypertensive nephrosclerosis-a cause of end-stage renal disease?
PMID- 11007816
TI - Acute renal failure related to the crush syndrome: towards an era of seismo
nephrology?
PMID- 11007817
TI - Malnutrition and the acute-phase reaction in dialysis patients-how to measure and
how to distinguish.
PMID- 11007818
TI - End-stage renal disease and erectile dysfunction. Is there any hope?
PMID- 11007819
TI - The management of chronic renal insufficiency in the conservative phase.
PMID- 11007820
TI - Effects of pentoxifylline, pentifylline and gamma-interferon on proliferation,
differentiation, and matrix synthesis of human renal fibroblasts.
AB - BACKGROUND: Kidneys that progress to end-stage renal failure are almost
invariably characterized by the presence of tubulointerstitial fibrosis.
Therapeutic interventions to halt the progressive deterioration of renal function
are still limited. Pentoxifylline, pentifylline, and gamma-interferon have shown
a potential benefit in the treatment of fibrotic processes in the skin and lung.
Thus, the aim of the present study was the analysis of potential anti-fibrotic
effects of these substances on human kidney fibroblasts in vitro. METHODS:
Primary renal fibroblasts were established from human kidney biopsies and were
studied in addition to two renal fibroblast cell lines. Cells were first growth
arrested by withdrawal of fetal calf serum (FCS) and subsequently stimulated with
10% FCS in the presence of different concentrations of pentoxifylline (PTX),
pentifylline (PTF), or gamma-interferon (IFN-gamma). Fibroblast proliferation was
determined by bromodeoxyuridine incorporation and cell counts. Northern and
western blot hybridizations for basic fibroblast growth factor (FGF)-2 and
transforming growth factor (TGF)-beta1 were performed to analyse inhibitory
effects. The effects of all three substances on matrix synthesis were evaluated
by immunoblot analyses and ELISA for collagen type I and fibronectin after
stimulation with TGF-beta1. Finally, differentiation into myofibroblasts was
examined by double immunofluorescence staining for alpha-smooth-muscle actin and
Hoechst dye H33258. RESULTS: PTX and PTF resulted in a dose- and time-dependent
inhibition of proliferation in all fibroblast lines (maximum 78.9+/-6.2% at 500
microg/ml PTX). Conversely, IFN-gamma had only modest effects on fibroblast
proliferation, resulting in a maximum of 36.0+/-6.1% inhibition at 500 U/ml.
Northern blot hybridizations determined that FGF-2 mRNA levels in fibroblasts
were decreased up to 73.7 and 91.5% by PTX (1000 microg/ml) and PTF (100
microg/ml), whereas IFN-gamma led to a reduction of 46.2% at 1000 U/ml,
indicating that the inhibitory effects of all three substances may be mediated
through inhibition of FGF-2 synthesis. These findings were corroborated by
immunoblot analyses where again PTX and PTF had the strongest inhibitory effects.
No change in TGF-beta1 mRNA levels was noted. Synthesis of cellular and secreted
collagen type I was robustly inhibited by PTX and PTF, whereas IFN-gamma exerted
the strongest inhibitory effect on fibronectin synthesis and secretion. In
addition, IFN-gamma down-regulated the expression of alpha-smooth-muscle actin up
to 73.3% (at 1000 U/ml) whereas PTX and PTF resulted in a down-regulation of up
to 49.7+/-1.8 and 80.0+/-4.4% (at 1000 and 100 microg/ml) respectively. PTF was
in all experiments about 10 times more potent than equimolar concentrations of
PTX. CONCLUSIONS: PTX and PTF exerted robust inhibitory effects on fibroblast
proliferation, extracellular matrix synthesis, and myofibroblastic
differentiation. Conversely, IFN-gamma caused strong inhibition of fibronectin
synthesis and alpha-smooth-muscle cell actin expression but had only weak
inhibitory influences on fibroblast proliferation and collagen type I synthesis.
Inhibitory effects of all three substances on proliferation may be mediated
through inhibition of FGF-2 synthesis.
PMID- 11007821
TI - Glomerular function and morphology in puromycin aminonucleoside nephropathy in
rats.
AB - BACKGROUND: The most characteristic manifestation of minimal-change nephropathy
is podocyte cell process broadening. In a previous study in children from our
unit, we found an inverse correlation between foot process width, glomerular
filtration rate (GFR), and filtration fraction. The aim of the present study was
to determine whether this relationship also existed in the puromycin
aminonucleoside (PAN) experimental model. METHODS: Sixteen Munich-Wistar-Fromter
male rats initially weighing median 247 g (range 171-286) were used. Four rats
served as controls. The other 12 rats were divided into three groups receiving
daily subcutaneous injections of 1, 1.67, and 2.5 mg PAN/100 g body weight
respectively, for 6 days. GFR was determined by clearance of inulin and the
fractional urine albumin excretion was measured. Standard stereological methods
were used to estimate the glomerular volume, the mean foot process width and the
length density of slit pores. RESULTS: GFR decreased with increasing PAN doses.
The glomerular volume was increased in the group receiving the lowest PAN dose,
while it was decreased in the group with the highest PAN dose, compared with
controls. The fractional albumin excretion and the foot process width increased
and the total slit pore length decreased with increasing doses of PAN. GFR
correlated directly with the glomerular volume as did the foot process width with
the fractional albumin excretion. The foot process width correlated inversely
with the glomerular volume as did the glomerular volume with the fractional
albumin excretion, and GFR with foot process width. CONCLUSIONS: The decreased
GFR found in the nephrotic rats was inversely related to foot process width and
directly related to glomerular volume, confirming our previous results in
children in an early stage of the nephrotic syndrome.
PMID- 11007822
TI - Antibody-induced modulation of the leukocyte CD11b integrin prevents mild but not
major renal ischaemic injury.
AB - BACKGROUND: CD11/CD18 beta(2) integrins are involved in leukocyte adhesion to the
activated endothelium, and therefore represent a possible therapeutic target in
the prevention of ischaemic acute renal failure (ARF). METHODS: To assess the
effect of an anti-CD11b monoclonal antibody (mAb) in ischaemic ARF,
uninephrectomized Fischer rats were subjected to 45 or 60 min of warm renal
ischaemia, then received 1 mg of anti-CD11b mAb 5 min before reperfusion.
RESULTS: After 45 min of ischaemia, renal function tests at 24 and 48 h were less
altered in mAb-treated than in control rats, but after 60 min of ischaemia the
same level of renal insufficiency was observed in the two groups. In parallel,
milder tubular necrosis and less leukocyte infiltration were observed in the
treated group after 45 min of ischaemia, but no difference was seen after 60 min
compared to the control group. The mAb was detected on blood neutrophils up to 48
h after infusion and a marked down-regulation of CD11b expression on neutrophil
surfaces was documented by flow cytometry. CONCLUSION: These results indicate
that anti-CD11b mAb administered prior to reperfusion decreases moderate
ischaemic ARF but fails to prevent renal injury secondary to prolonged ischaemia
in this model.
PMID- 11007823
TI - Identification and kinetics of leukocytes after severe ischaemia/reperfusion
renal injury.
AB - BACKGROUND: Leukocyte adhesion/infiltration in response to renal
ischaemia/reperfusion (I/R) injury is a well-known but poorly understood
phenomenon. The identification, kinetics, and exact role of these inflammatory
cells in I/R injury and regeneration are still matters of debate. METHODS:
Uninephrectomized rats were submitted to 60 min renal ischaemia by clamping of
renal vessels. RESULTS: Severe acute renal failure was observed, with maximum
functional impairment on day 2. By 12 h after the ischaemic event, up to 80% of
proximal tubular cells in the outer stripe of outer medulla (OSOM) were already
severely damaged. Proliferation (proliferating cell nuclear antigen (PCNA)
staining) started after 24 h, reaching maximum activity on day 3. Regeneration of
tubular morphology started on the 3rd day, and after 10 days 50% of tubules had
regenerated completely. Interstitial leukocytes (OX-1 immunohistochemical
staining) were already prominent at day 1, thereafter gradually increasing with
time. The so-called neutrophil-specific identification methods (myeloperoxidase
(MPO), chloroacetate esterase, mAb HIS-48) proved to be non-specific, since they
also stained for macrophages, as demonstrated by flow cytometry and the
combination of these stainings with the macrophage-specific ED-1 staining. MPO
activity was already significantly increased at 1 h post-I/R (439+/-34%,
P<0.005), reaching its maximum activity after 12 h of I/R (1159+/-138%,
P<0.0005), declining thereafter. On the other hand, neutrophil presence
investigated by H&E staining revealed only a few neutrophils in glomeruli,
medullary rays, and OSOM at 24 h after the ischaemic event (4.7+/-4.2 cells/mm(2)
vs controls=2.3+/-2.0 cells/mm(2) (n.s.)), and remained unchanged over the next
10 days. In contrast, significant monocyte/macrophage adhesion/infiltration (ED-1
staining) occurred at the OSOM at 24 h post-ischaemia (at 24 h, 120+/-46
cells/mm(2) vs. sham=18+/-4 cells/mm(2) (P<0.05)), became prominent at day 5
(1034+/-161 cells/mm(2) vs sham=18+/-18 cells/mm(2) (P<0.05)), and almost
disappeared after 10 days. CD4(+) cells (W3/25) gradually increased from day 5,
reaching a maximum at day 10. A few CD8(+) cells (OX-8) were apparent from days 3
until 10, but no B-cells (OX-33) were observed. CONCLUSIONS: After severe warm
I/R renal injury, a pronounced acute tubular necrosis occurs during the first 12
24 h in the absence of a marked cellular infiltrate, but with an important renal
MPO activity, reflecting the activation of the adhering inflammatory cells
(polymorphonuclear cells (PMNs) and mainly monocytes/macrophages). Only later at
the time and site (OSOM) of regeneration a sequential accumulation of
monocytes/macrophages and T cells becomes prominent, in contrast with the low
number of neutrophils found in the kidney during the 10-day post-ischaemic
period. The non-specificity of the so-called neutrophil-specific identification
methods (MPO activity, naphthol AS-D chloroacetate esterase, or mAb HIS-48
staining), cross-reacting with monocytes/macrophages, explains the controversy in
literature concerning the number of PMNs in post-ischaemic injury.
PMID- 11007824
TI - Renal function of children exposed to cyclosporin in utero.
AB - BACKGROUND: The use of cyclosporin (CsA) has improved graft survival in
transplant (Tx) patients despite its potential nephrotoxicity. Children born to
transplanted women may present with intrauterine growth retardation (IUGR). On
the basis of potential reduced nephron mass both in IUGR and in newborn
experimental animals exposed to CsA in utero, we investigated the renal function
of children >1 year of age born to women under maintenance immunosuppression,
including CsA. METHODS: Fourteen children born to 12 Tx women (nine kidney, one
pancreas-kidney, one heart, one liver) were investigated using inulin clearance
(C(in)), para-aminohippuric acid clearance (C(PAH)), microalbuminuria, and
electrolyte reabsorption rate. RESULTS: Gestational age of the 14 infants was
34+/-3 weeks and birth weight 2018+/-620 g. During pregnancy, CsA trough blood
level was 234+/-115 microg/l and plasma creatinine range was 96-136 micromol/l.
Two children were excluded from the study because renal investigation led to a
diagnosis of hereditary nephritis (one Alport syndrome, one familial dominant
focal segmental glomerulosclerosis) that was retrospectively completed in the
mother. Renal function tests were finally performed in 12 children at 2.6+/-1.8
years of age: BP 94+/-7/55+/-5 mmHg, C(in) 117+/-28 ml/min/1.73 m(2), C(PAH)
545+/-124 ml/min/1.73 m(2), filtration fraction 0.23+/-0.03, microalbuminuria
4.2+/-3.5 mg/mmol. Electrolyte tubular reabsorption rates and urine concentrating
capacity were normal. CONCLUSION: These results suggest that in children born to
transplanted women taking CsA, renal function develops normally despite prolonged
exposure in utero.
PMID- 11007825
TI - Determinants of urinary excretion of Tamm-Horsfall protein in non-selected kidney
stone formers and healthy subjects.
AB - BACKGROUND: The aim of the study was to measure urinary excretion of Tamm
Horsfall protein (THP), an important inhibitor of crystallization, and to
identify possible determinants of urinary THP excretion in non-selected kidney
stone formers (SF) and healthy subjects (C). METHODS: By means of a commercially
available ELISA (Pharmacia and Upjohn/Elias, Germany), we measured THP in 24-h
urines of 104 SF (74 males/30 females, age 16-74 years) who had formed 8.7+/-2.4
stones (range 1-240), and of 71 C (41 males/30 females, age 22-62 years). Types
of stones formed by SF were 88 calcium, eight uric acid, six infection, and two
cystine. All values are means+/-SE. RESULTS: The normal range (5th to 95th
percentile) of U(THP)xV was 9.3-35.0 mg/day in males and 9.0-36.3 mg/day in
females respectively. Mean U(THP)xV was 21.3+/-1.2 mg/day (range 3. 4-51.6) in
male and 15.2+/-1.6 mg/day (range 1.8-32.3) in female SF (P=0.008 vs male SF).
Since U(THP)xV was positively correlated with C(Crea) (r=0.312, P=0.001) in SF as
well as with U(Crea)xV (r=0.346, P=0.0001) and with body surface (r=0.271,
P=0.0003) in all study subjects, mean THP/Crea (mg/mmol) was used for all further
calculations. Overall, THP/Crea was lower in SF (1.42+/-0.07 vs 1. 68+/-0.08,
P:=0.015), mainly due to increased THP/Crea in female C (2.08+/-0.11, P=0.0036 vs
female SF, P=0.0001 vs male C and vs male calcium SF), which also explains
decreased THP/Crea values in calcium SF (1.46+/-0.08, P=0.041 vs C). In addition,
THP/Crea was reduced in uric acid SF (1.11+/-0.21, P=0.049 vs C). Whereas
THP/Crea was not related to age, urine volume, intake of dairy calcium, or
urinary markers of protein intake, either in C or in SF, it correlated
significantly with urinary Citrate/Crea, both in C (r=0.523, P=0.0001) and in SF
(r=0.221, P=0.025). In C only, but not in SF, THP/Crea was correlated with
urinary Calcium/Crea (r=0. 572, P=0.0001) and with Oxalate/Crea (r=0.274,
P=0.022). CONCLUSIONS: Both in C and SF, urinary THP excretion is related to body
size, renal function and urinary citrate excretion, whereas dietary habits
apparently do not affect THP excretion. Uric acid and calcium stone formation
predict reduced THP excretion in comparison with C, whereas female gender goes
along with increased urinary THP excretion in C. Possibly most relevant to kidney
stone formation is the fact that THP excretion rises only in C in response to
increasing urinary calcium and oxalate concentrations, whereas this self
protective mechanism appears to be missing in SF.
PMID- 11007826
TI - Intestinal protein loss in patients with haemorrhagic fever with renal syndrome.
AB - BACKGROUND: In haemorrhagic fever with renal syndrome (HFRS) vascular dysfunction
has been observed in various organs, but the involvement of the intestine has not
yet been reported. This study was performed to evaluate the association of
intestinal protein loss in this disease with other clinical parameters reflecting
vascular permeability or disease severity. METHODS: Twenty patients with HFRS
were included in this study. Intestinal protein loss was measured by (99m)Tc
human serum albumin ((99m)Tc-HSA) scintigraphy in the acute stage, and
quantitative analysis of protein loss was measured by the faecal clearance of
alpha 1-antitrypsin (C(AT)) in the acute and the recovery stages. C(AT) was then
compared with clinical parameters reflecting disease activity and vascular
permeability. RESULTS: (99m)Tc-HSA scintigraphy was positive in 13 (65%)
patients, and C(AT) in the acute stage was significantly increased as compared
with C(AT) in the recovery stage (40.5+/-24.1 vs 9.2+/-4.2 ml/day, P<0.001).
C(AT) was associated with serum albumin levels, frequency of hypotensive
episodes, severity of acute renal failure, and degree of thrombocytopenia.
CONCLUSIONS: Our data suggest that the increased vascular permeability of HFRS is
associated with the increased intestinal loss of plasma proteins, which might
represent one of the parameters of disease severity in HFRS.
PMID- 11007827
TI - Incidence and outcome of pauci-immune rapidly progressive glomerulonephritis in
Wessex, UK: a 10-year retrospective study.
AB - BACKGROUND: The Wessex Renal Unit serves a large stable population (2.5 million).
Pauci-immune rapidly progressive glomerulonephritis (RPGN) is a frequent cause of
acute renal failure requiring admission to our unit ( approximately 8%). At a
population level, little is known of the epidemiology and outcome of RPGN.
METHODS: Between 1 April 1986 and 31 March 1996, 141 cases of biopsy proven pauci
immune RPGN were seen in the Wessex region. The records of 128 patients were
reviewed. Median (range) follow-up was 1.8 (0.9-9.64) years from diagnosis.
RESULTS: The incidence of 4 per million was stable throughout the period. No
clustering was seen. The diagnosis was made (median, 25th, 75th centile) 78.5
(45, 166) days after symptom onset. Co-morbidity (mostly hypertension) was seen
in 47% of patients. Other organs affected were lungs 63%, nose/sinuses 50%,
joints 42%, muscle 33%, skin 22% and nervous system 14%. Anti-neutrophil
cytoplasmic antibody (ANCA) was positive in 73%; cytoplasmic ANCA 34%, peri
nuclear ANCA 26% and undifferentiated 14%. Twenty-seven per cent tested ANCA
negative. The differences between the groups were small; time to diagnosis was
shorter in the ANCA negative (-ve) group (P=0.02) and there were more airway
symptoms in the ANCA positive (+ve) group (P:<0.05). All biopsies demonstrated a
necrotizing process; crescents were seen in 96% involving (mean+/-SD) 54+/-26% of
the glomeruli. Creatinine concentration (mean+/-SD) at diagnosis was 806+/-540
micromol/l. Treatment followed established immunosuppressive regimens. Initial
dialysis was required by 59%, 36% needing long-term dialysis. At 1 year 68% were
alive. The need for dialysis (P=0.0004) and age (P=0. 004) were poor prognostic
markers. Ten per cent were transplanted, graft survival was 90% at 1 year, no
recurrence was seen. CONCLUSIONS: This study, looking at a large cohort, has
established the incidence and outcome of ANCA +ve and ANCA -ve RPGN in a defined
stable population. It stresses the similarities between ANCA +ve and ANCA -ve
cases and supports the notion that pauci-immune RPGN is part of a continuum of
vasculitic illness. In this series transplantation is a safe option.
PMID- 11007828
TI - Anti-laminin auto antibodies in ANCA-associated vasculitis.
AB - BACKGROUND: Endothelial cell damage occurs during vasculitic processes in vivo.
With the alteration of the endothelium, exposure to basement membrane components
may occur with induction of humoral immunity. METHODS: In the present study, we
evaluated the prevalence of antibodies against the basement membrane antigen
laminin (LMN) in patients with ANCA-associated systemic vasculitis (AASV),
pathologic controls (systemic lupus erythematosus, mixed cryoglobulinaemia,
Henoch-Schonlein purpura, primary glomerulonephritis) and normal individuals.
RESULTS: By ELISA, 21.6% of AASV (16/74) and 10% of pathologic controls (3/30),
but only one of the normal controls (2. 8%) had these antibodies (P=0.02). When
AASV patients were divided into two groups according to diagnosis and ANCA
antigen specificity, antibodies to LMN were found in 27.5% of MPO-ANCA positive
microscopic polyangiitis patients (11/40) vs. only 14.7% of PR3-ANCA positive
Wegener granulomatosis patients (5/34). There was no correlation between the
presence or titre of anti-LMN antibodies and the main clinical and laboratory
parameters. CONCLUSION: These results indicate that basement membrane antigens
may become immunogenic in patients with AASV, especially in those with MPO-ANCA
positivity. These antibodies are most likely the result of endothelial damage
secondary to the initial inflammatory process but may well perpetuate further
vascular damage in some patients.
PMID- 11007829
TI - Predictors of renal outcome in diffuse proliferative lupus nephropathy: data from
repeat renal biopsy.
AB - BACKGROUND: Diffuse proliferative lupus nephropathy (DPLN) is the most frequent
and severe form of renal disease in patients with systemic lupus erythaematosus.
Histological parameters at the initial biopsy of patients with DPLN that would
predict the progression of renal pathology or function at the second biopsy are
not clearly defined. METHODS: The prognostic significance of renal histological
indices, such as glomerular activity index and volume density of cortical
interstitium [Vv(int/cortex)], was evaluated from successive renal biopsies in 21
patients with DPLN. RESULTS: At the time of the second biopsies, performed an
average of 43 months after the first biopsies, seven patients (33%) showed
progressive renal insufficiency. Only three cases (14%) transformed to World
Health Organization class I or III. The seven patients with clinical progression
exhibited a higher frequency of hypertension, higher percent glomerulosclerosis,
and larger Vv(int/cortex) at the time of second biopsy as compared with the 14
patients without renal insufficiency. At the first biopsy, patients with clinical
progression showed a higher glomerular activity index (2.9+/-1.2 vs 1.3+/-0.8,
P<0.05) and larger Vv(int/cortex) (0.13+/-0.07 microm(3)/microm(3) vs 0.05+/-0.03
microm(3)/microm(3), P<0.05) than the patients without progression. The
glomerular activity index at the first biopsy correlated directly with per cent
glomerulosclerosis, Vv(int/cortex), and serum creatinine level at the second
biopsy. Vv(int/cortex) in the first biopsy also showed a significant relation
with per cent glomerulosclerosis and serum creatinine level at the second biopsy.
CONCLUSIONS: These results suggest that higher glomerular activity and larger
interstitial volume density at the initial biopsy can predict future progression
of renal pathology or function in DPLN.
PMID- 11007830
TI - Follow-up study of glomerular dimensions and cortical interstitium in
microalbuminuric type 1 diabetic patients with or without antihypertensive
treatment.
AB - BACKGROUND: A decrease in urinary albumin excretion is regularly seen with
antihypertensive treatment in patients with diabetic nephropathy. Our study
concerns structural data obtained by light microscopy in baseline and follow-up
biopsies in antihypertensive treated patients and in a reference group. METHODS:
Microalbuminuric type 1 diabetic patients with diabetes duration of 6-16 years
were studied. Two groups, allocated to treatment with either angiotensin
converting enzyme-inhibitor (group 1, n=6) or beta-blocker (group 2, n=6) after
the baseline biopsy, were studied in parallel, whereas the reference group (group
3, n=9), without antihypertensive treatment, was part of a previously completed
study. The renal plastic-embedded biopsies were serially sectioned (1 microm),
the sections being used for determining glomerular volume, vascular pole area,
and interstitial space expressed as fraction of tubular cortex. RESULTS: A
significant increase in glomerular volume (P=0.04) was seen in group 3 only.
Vascular pole area (VPA) and VPA relative to calculated glomerular surface did
not show significant changes in any of the groups, only a tendency to increase in
VPA in group 3 (P=0.051). The increase in VPA correlated with systolic blood
pressure during the study period (r=0.49, P=0.03). Glomerular volume did not
correlate with HbA(1C), current diabetic glomerulopathy, or ensuing worsening of
glomerulopathy. In group 3 every case showed an increase in interstitium
(P=0.0009), group 2 showed a decrease (P=0.03), and group 1 showed no change.
Increase in interstitial fractional volume correlated with diastolic blood
pressure during the study (r=0.54, P=0.01). CONCLUSIONS: In early
microalbuminuria, type 1 diabetic patients show glomerular growth, probably
compensatory to the developing glomerulopathy. The increase in interstitial
volume fraction, demonstrable in early nephropathy, is further augmented over a
few years, but is arrested by antihypertensive treatment.
PMID- 11007831
TI - ACE DD genotype is more susceptible than ACE II and ID genotypes to the
antiproteinuric effect of ACE inhibitors in patients with proteinuric non-insulin
dependent diabetes mellitus.
AB - BACKGROUND: ACE polymorphism, especially genotype DD or D allele, may be involved
in the progression of diabetic nephropathy. It may also have different effects on
the reduction of proteinuria by ACE inhibitors in patients with proteinuria. We
investigated the relationship between ACE gene polymorphism and antiproteinuric
effect of ACE inhibitors (Benazepril 10 mg/day or Perindopril 4 mg/day) in 83
NIDDM patients with overt proteinuria (urinary protein excretion over 500
mg/day). METHODS: We recruited NIDDM patients with overt proteinuria from our
renal clinic. Before entry, previously used ACE inhibitors were withdrawn for at
least 2 weeks and baseline proteinuria and albuminuria were measured. Patients
were classified into three groups in accordance with ACE genotypes (17 DD; 33 ID;
33 II) and prospectively followed up for 3 months. Various clinical parameters
including age, DM duration, body mass index (BMI), 24-h urine sodium, protein and
albumin, BUN, serum creatinine, creatinine clearance (Ccr), mean arterial
pressure (MAP), and HbA(1c) were measured in the pre- and post-treatment periods.
ACE genotypes were determined by polymerase chain reaction. RESULTS: There were
no significant differences in the clinical parameters such as age, DM duration,
BMI, BUN, serum creatinine, Ccr, MAP, HbA(1c), and daily urinary excretion of
sodium, protein and albumin among three groups (P>0.05). After the 3-month
treatment period using ACE inhibitors, there were no significant differences in
the reduction of MAP and Ccr among the three groups (P>0.05). However, the
percentage reductions in urinary excretion of protein and albumin for DD genotype
were significantly higher than in ID and II genotypes (50.9+/-19.2% vs 19.2+/
16.0%, 20.2+/-20.4%; 52.6+/-23.6% vs. 13.5+/-51.8%, 24.8+/-23.9%, P<0.05). There
were no statistically significant correlations between the levels of baseline
proteinuria and albuminuria and the magnitudes of the reduction of proteinuria
and albuminuria under ACE inhibition (P>0.05). CONCLUSIONS: Our results suggest
that the ACE gene polymorphism might have a role in determining the
responsiveness to the antiproteinuric effect of ACE inhibition in proteinuric
NIDDM patients.
PMID- 11007832
TI - Elevated serum levels of soluble adhesion molecules predict death in pre-dialysis
patients: association with malnutrition, inflammation, and cardiovascular
disease.
AB - BACKGROUND: Atherosclerotic cardiovascular disease, malnutrition, and increased
levels of pro-inflammatory cytokines are common features in patients with chronic
renal failure, and contribute to the high mortality rate observed in these
patients. A diverse group of soluble cellular adhesion molecules (CAM) (sVCAM-1,
sICAM-1 and sE-selectin) are expressed on the surface of vascular endothelial
cells in response to pro-inflammatory cytokines and may play an important role in
the atherogenic process. METHODS: Serum levels of sVCAM-1, sICAM-1 (n=87) and sE
selectin (n=71) were analysed in a cohort of 88 patients (50+/-1 years) with
chronic renal failure. The presence of malnutrition (subjective global assessment
(SGA) and serum albumin), inflammation (C-reactive protein (CRP), tumour necrosis
factor-alpha (TNF-alpha), and serum hyaluronan), and cardiovascular disease (CVD)
were assessed at a time-point close to the start of dialysis treatment (GFR 7+/-1
ml/min). Blood lipid parameters were also assessed. RESULTS: Significant
correlations were observed between Log high-sensitivity CRP (hsCRP) and sVCAM-1
(R=0.39; P<0.01) and sICAM-1 (R=0.47; P:<0.001) levels but not between Log hsCRP
and sE-selectin levels in 60 patients examined with a hsCRP assay. Also serum
concentrations of Log hyaluronan correlated significantly to sVCAM-1 (R=0.34;
P<0.01) and sICAM-1 (R=0.29; P<0.05) levels. Malnourished patients (SGA>1) had
elevated serum concentrations of sVCAM-1 (1436+/-94 vs. 1105+/-53 ng/ml; P<0.01)
compared to well-nourished patients (SGA 1). Patients with clinical signs of CVD
(n=26) had elevated serum levels of sICAM-1 (282+/-18 vs. 242+/-9 ng/ml; P<0.05)
compared to 61 patients without signs of CVD. Plasma Log lipoprotein (a) (Lp(a))
levels correlated significantly with sVCAM-1 (R=0.30; P<0.01). Survival analysis
by the Cox regression model showed that elevated sICAM-1 was, independent of age,
SGA, CVD, and Log CRP, significantly related to an increased mortality rate.
CONCLUSIONS: Elevated serum concentrations of soluble adhesion molecules are
found in pre-dialysis patients who are malnourished, inflamed, and have signs of
cardiovascular disease. These data also suggest that sICAM-1 is an independent
predictor of mortality in pre-dialysis patients. Further studies are needed to
determine if inflammation causes accelerated atherogenesis via effects on soluble
adhesion molecules or if elevated serum levels of soluble adhesion molecules are
merely markers of endothelial activation in patients with chronic renal failure.
PMID- 11007833
TI - Heparins and blood polymorphonuclear stimulation in haemodialysis: an expansion
of the biocompatibility concept.
AB - BACKGROUND: At the concentrations used in haemodialysis and in a dose-dependent
way, unfractionated heparin (UFH) and, to a lesser degree, a low-molecular-weight
heparin (LMWH) stimulate polymorphonuclear cells (PMN) in vitro, and could act in
synergy with the stimulatory effect of dialysis membranes in vivo. To examine
this hypothesis, we studied the effects of different heparin types and regimens
on blood PMNs during haemodialysis sessions. METHODS: Ten haemodialysed patients
were studied during regular dialysis sessions on a cellulose triacetate membrane
(CT 110 G; 1.10 m(2); Baxter), with four different random heparin protocols: one
high-UFH regimen (HHR) at 90 IU/kg body-weight (b.w.) and one low-UFH regimen
(LHR) at 50 IU/kg b.w., and with a LMWH (nadroparin calcium) at 85 (HHR) or 45
(LHR) IU/kg b.w. Blood granulocytes, platelet counts, and plasma granulocyte
degranulation products (elastase, lactoferrin) were measured serially during 4 h
dialysis sessions. RESULTS: After 10 min, the reduction in PMNs with UFH was
29.5% for HHR (P<0.01) and 28.5% for LHR (P<0.01), and only 16.8 and 18.6% with
LMWH (NS), significantly higher for HHR with UFH than with LMWH (P<0.01). At 60
min, the elastase increase with HHR was greater, 61% with UFH (P<0.01) and 37.8%
with LMWH (P<0.01), significantly higher than LHR for UFH (P<0.05) or LMWH
(P<0.05). The overall decrease in platelets (with LMWH P<0.01) and the overall
increase in lactoferrin (P<0.001) were not different between heparinization
procedures. CONCLUSION: Under a conventional heparin regimen, the PMN variation
during the course of the dialysis session suggests a more biocompatible effect of
LMWH over UFH. In addition, the variation of elastase favours the lower dose,
whatever the type of heparin. Heparin type and dose should therefore be
considered in studies addressing biocompatibility in haemodialysis: a low dose of
LMWH may be viewed as a better biocompatible treatment with regard to leukocyte
stimulation.
PMID- 11007835
TI - Stewardship or clinical freedom? variations in dialysis decision making.
AB - BACKGROUND: It is generally agreed that acceptance criteria for dialysis have
varied and changed over time and that implicit rationing, to some extent forced
on clinicians by limited capacity, has been widely practised. Our objective was
to study the basis and extent of variation in dialysis decision making among
nephrologists in one NHS region. DESIGN AND METHODS: In a clinical judgement
analysis, linear regression models were employed to reflect the impact of
clinical and non-clinical cues on nephrologists' decisions to offer dialysis to
60 'paper patients' under current capacity constraints and under an assumption of
no capacity limit. A short questionnaire was also completed by eight
nephrologists to elicit their expressed decision drivers, which were subsequently
compared with those tacitly derived from the appraisal of the 60 clinical
vignettes. RESULTS: Doctors showed substantial variation in their propensity to
offer dialysis and in their perceptions of the benefits of dialysis. Even for the
five patients where the discordance in propensity to offer dialysis was least,
the range in perceived gain in life expectancy was from 24 to 264 months (mean 91
months). The decision models had relatively good explanatory power with an
average r(2) of 0.67 (0.39-0.90) and 0.70 (0.47-0.95) for decisions made under
current capacity constraints and under an assumption of no limit capacity
respectively. Surprisingly, for most doctors, the patient's age had very little
impact on dialysis decisions but the magnitude of the beta-coefficients for the
patient's mental state (mean -30.7) was of a similar order of magnitude to the
coefficient for the principal 'renal' drivers (e.g. the mean coefficient for
uraemic symptomatology under current capacity constraints was 47.7). The
influence of other non-renal factors on the doctor's likelihood to offer dialysis
was largely independent of the capacity assumption. A comparison of the doctor's
stated decision drivers with those tacitly derived from their decision models
showed only modest correlation. CONCLUSIONS: The extent to which doctors vary in
their propensity to offer dialysis is substantial. Very few non-clinical cues
appear to influence the decision to offer dialysis. The most important non-renal
factor in determining dialysis decisions was the patient's mental state.
PMID- 11007834
TI - Role of complement and platelet-activating factor in the stimulation of
phagocytosis and reactive oxygen species production during haemodialysis.
AB - BACKGROUND: Neutrophil phagocytic functions have been studied extensively in
haemodialysis (HD) patients; however, results are contradictory and the
mechanisms that modulate phagocytosis and oxidative burst during dialysis are not
completely understood. METHODS: The present study investigated neutrophil
functions in a selected population of patients before and during clinical
dialysis with cuprophane, and polyacrylonitrile (AN69) membranes. We measured
phagocytosis of Escherichia coli and intracellular hydrogen peroxide (H2O2)
production by flow cytometry in whole blood. RESULTS: Before dialysis,
neutrophils from HD patients showed normal phagocytic capability and H2O2
formation. Phagocytosis of FITC-E. coli was significantly stimulated in
cuprophane but not AN69-treated patients. Spontaneous and stimulated H2O2
production was enhanced with both cuprophane and AN69 membranes. We then
investigated in vitro the role of complement and platelet-activating factor (PAF)
in the activation of neutrophils. Incubation of whole blood with C5a increased
phagocytosis but not H2O2 production. On the contrary, the addition of synthetic
PAF showed a markedly stimulated H2O2 production without increase in
phagocytosis. Moreover, during dialysis with formaldehyde-reused cuprophane,
complement activation was abolished and phagocytosis was no longer enhanced,
while the stimulation of H2O2 production persisted. In addition, we also excluded
a particular role of the membrane itself in the activation of neutrophils.
CONCLUSION: We demonstrated that in a selected population of HD patients,
neutrophils exhibit normal phagocytic capability and normal intracellular H2O2
production. During dialysis, the stimulation of phagocytosis observed with
cuprophane is complement dependent, whereas the enhanced H2O2 production observed
with both cuprophane and AN69 membranes might be related to PAF production.
PMID- 11007836
TI - Impaired glucose oxidation and glucose-induced thermogenesis in renal transplant
recipients.
AB - BACKGROUND: Renal transplant recipients often show various metabolic
abnormalities including reduced glucose tolerance, impaired insulin sensitivity
and altered lipid metabolism. However, the acute effects of carbohydrate
ingestion on substrate utilization and energy expenditure have not been fully
elucidated. METHODS: We evaluated: (i) basal energy expenditure (EE) and
substrate utilization, (ii) metabolic fate of an oral glucose load, and (iii)
substrate-induced thermogenesis in: (a) 15 non-diabetic renal transplant
recipients (Tx) (BMI 25+/-1) on triple immunosuppressive therapy, (b) 11 patients
with primary glomerulonephritis (BMI 25+/-1) (Cort) receiving prednisone
treatment, and (c) 12 healthy subjects (BMI 26+/-1) (N). Continuous indirect
calorimetry was performed in the basal post-absorptive state for 60 min and
continued for an additional 180 min following an oral glucose load (75 g).
RESULTS: In the basal state, EE was similar in the three study groups. It
averaged 14.6+/-0.7, 15.7+/-1.3, and 14.1+/-0.8 cal/kg/min in Tx, Cort, and N
respectively. Glucose oxidation was higher in N (1.3+/- 0.2 mg/kg/min) than in Tx
(0.7+/-0.2) and Cort (1.0+/-0.2) (P<0.05 in N vs. Tx and vs. Cort), whereas lipid
oxidation was lower in N (0.6+/-0.1 mg/kg/min) than in Tx (0.9+/-0.1) and Cort
(0.9+/-0.05) (P<0.03 in N vs. Tx and vs. Cort). After glucose ingestion, total
carbohydrate oxidation averaged 21.2+/-2, 31.0+/-3, and 29.6+/-3 g, which
represented 28+/-3, 41+/-3 and 39+/-2% of the total glucose load in Tx, Cort and
N respectively (P<0.01 Tx vs Cort and N). The cumulative increase of EE (180 min)
was 9.7+/-2, 13.2+/-3 and 13+/-3 kcal in Tx, Cort, and N respectively.
CONCLUSIONS: The present data show that in non-diabetic renal transplant
recipients basal EE is normal. However, basal lipid oxidation is higher and
glucose oxidation is lower than in healthy subjects. In addition, the oxidative
disposal of a glucose load and substrate-induced thermogenesis are impaired.
PMID- 11007837
TI - The 825C/T polymorphism of the G-protein subunit beta3 does not influence blood
pressure and renal function in kidney transplant recipients.
AB - BACKGROUND: Recently, a polymorphism at position 825 (C-->T) of the cDNA that
encodes the beta3 subunit of heterotrimeric G proteins (Gbeta3) was found to be
associated with essential hypertension. The T allele leads to the formation of a
truncated splice variant (Gbeta3-s) with enhanced activity, promoting
hypertension. We examined whether the T allele had an influence on blood pressure
(BP) and early renal function after renal transplantation. METHODS: We determined
the Gbeta3 genotype and T allele frequencies in renal transplant patients and
examined associations with BP, BP medications, and renal function in the first
year after transplantation. RESULTS: In renal transplant recipients (n=216) the
frequency of the T allele was marginally increased (0.34 vs 0.29) compared with
normal healthy blood donors (n=163). Age, sex and body mass index were similar in
patients with the CC, CT and TT genotype. BP, number of BP medications, and serum
creatinine levels were also similar for the three genotypes within the first year
after transplantation. Significantly more patients with the TT genotype (48%) had
glomerulonephritis as the underlying renal disease, compared with the CT (29%)
and CC (27%) genotypes. CONCLUSIONS: The T allele of Gbeta3 does not have a
negative impact on BP and early renal function in recipients of a renal
allograft. The T allele might play a role in the pathogenesis of chronic
glomerulonephritides.
PMID- 11007838
TI - Workload generated by a living donor programme for renal transplantation.
AB - BACKGROUND: The ethical and medical implications of live kidney donation result
in a comprehensive work-up process. The aim of this study was to determine the
magnitude of the workload and the yield of renal transplants generated by a live
donor programme. METHODS: Referrals to the Leicester live donor programme over
the five-year period 1994-1998 were retrospectively assessed. These were
initiated by nephrology referral and subsequently investigated in a stepwise
manner. Patients were counselled and baseline tests performed prior to consultant
surgeon review and assessment of donor renal function/anatomy. RESULTS: One
hundred and fifty referrals consisting of 150 recipients with 269 potential
donors were originally made. This resulted in 32/120 (27%) related and 3/30 (10%)
unrelated recipients (P=0.06) and 32/220 (15%) related and 3/49 (6%) unrelated
donors proceeding to live donor transplantation, with a mean work-up time (+/-SD)
of 9 (+/-7) months. One hundred and fifteen recipients (77%) and 234 (87%) donors
failed to proceed at various stages of assessment, for a variety of
immunological, medical and social reasons. A large number of expensive
immunological investigations were required for potential donors, the majority of
which did not proceed to transplantation. However as a result of performing these
in the early stages of assessment the number of more invasive tests is kept to a
minimum. CONCLUSIONS: There is a relatively low yield of transplants from live
donor referrals, particularly those between unrelated individuals. The vast
majority of referrals fail to proceed for legitimate reasons, but as a result,
create a significant workload with notable staffing and financial implications.
PMID- 11007839
TI - Prevention of acute rejection with antithymocyte globulin, avoiding
corticosteroids, and delaying cyclosporin after renal transplantation.
AB - BACKGROUND: Despite their well-known side-effects, corticosteroids (Cs) are
currently used after kidney transplantation. Avoidance of Cs may improve patient
quality of life and eventual long-term survival. We report on a regimen using
antithymocyte globulin (ATG) and mycophenolate mofetil (MMF) for induction, and
cyclosporin (CsA) plus MMF for maintenance treatment of recipients of primary
kidney transplantation. METHODS: We studied 11 consecutive, non-sensitized renal
transplant patients (nine cadaver and two living donors). Initial
immunosuppression consisted of ATG (1.5 mg/kg/day, i.v.) given for 10 days and
MMF (1.0 g/b.i.d.). CsA (8 mg/kg, in two divided doses) was started on post
operative day 11. Cs were only allowed in the case of MMF discontinuation, for
the treatment of acute rejection, and in the event of recurrence of the primary
glomerulonephritis. RESULTS: All patients completed the entire 10-day ATG course.
Main side-effects included fever (>38 degrees C) and serum sickness, observed in
73 and 27% of the patients respectively. The incidence of acute rejection was 27%
(three of 11 patients). In two patients with acute rejection, serum sickness was
concomitantly diagnosed and renal histology was partially compatible with immune
complex disease. The remaining patient had two episodes of low-grade rejection.
All rejection episodes were rapidly reversed. Two patients (18%) were treated
with ganciclovir for cytomegalovirus (CMV) infection. Two patients (18%) are
currently receiving Cs for recurrence of the native glomerulonephritis and two
rejection episodes respectively. All patients are currently alive with
functioning kidneys (average follow-up of 8.4 months; average creatinine level of
128 micromol/l). CONCLUSION: This pilot study suggests that ATG induction in
combination with MMF and delayed introduction of CsA, in the absence of Cs, is
not well tolerated in recipients of kidney transplants. An earlier introduction
of calcineurin inhibitors and/or a shorter course of ATG may reduce the incidence
of fever and serum sickness secondary to ATG.
PMID- 11007840
TI - Mnemotechnical note on the use of Cockcroft creatinine clearance formula for the
validation of a 24-h urine collection.
PMID- 11007841
TI - Fibrillary/immunotactoid glomerulonephritis in HIV-positive patients: a report of
three cases.
PMID- 11007842
TI - Acute tubular necrosis in a patient with Waldenstrom's macroglobulinaemia and
hyperviscosity syndrome.
PMID- 11007843
TI - Absent pubertal development in a child with chronic renal failure: the case of
Frasier syndrome.
PMID- 11007844
TI - Tumoral calcinosis associated with pyrexia and systemic inflammatory response in
a haemodialysis patient: successful treatment using intravenous pamidronate.
PMID- 11007845
TI - The child with haematuria and dysphagia.
PMID- 11007847
TI - Cake kidney drained by single ureter: MAG3 renogram for diagnosis and function
follow-up.
PMID- 11007846
TI - Nephrotic syndrome after renal percutaneous transluminal angioplasty.
PMID- 11007848
TI - The simple renal cyst.
PMID- 11007849
TI - Unexplained hypertension in a previously normotensive dialysis patient.
Diagnosis: pheochromocytoma.
PMID- 11007850
TI - Hyponatraemia with natriuresis in neurosurgical patients.
PMID- 11007851
TI - Association of Bartter's syndrome with vasculitis.
PMID- 11007852
TI - C-reactive protein and cardiovascular disease: linked by complement?
PMID- 11007853
TI - Focal sclerosis with tip lesions secondary to polycythaemia vera.
PMID- 11007854
TI - Morphology of coronary atherosclerotic lesions in patients with end-stage renal
failure.
PMID- 11007855
TI - Renal infarction in a patient with von Willebrand disease.
PMID- 11007856
TI - Regression of nephrotic syndrome in amyloidosis of familial mediterranean fever
following colchicine treatment.
PMID- 11007857
TI - Elevating nephrology to a 'stenting' specialty.
PMID- 11007858
TI - Successful use of cyclosporin A in progressive anti-glomerular basement membrane
nephritis.
PMID- 11007859
TI - Haematological toxicity of midodrine in haemodialysis patients.
PMID- 11007860
TI - Hepatitis C and holiday dialysis. A postal survey of UK renal units.
PMID- 11007861
TI - The utility of AST/ALT ratio as a non-invasive demonstration of the degree of
liver fibrosis in chronic HCV patients on long-term haemodialysis.
PMID- 11007862
TI - Intravenous ascorbic acid in haemodialysis patients with functional iron
deficiency.
PMID- 11007863
TI - Changing relationships between serum IL-1, IL-6, and TNF-alpha and dynamic tests
of parathyroid gland function in haemodialysis patients with severe
hyperparathyroidism in response to calcitriol therapy.
PMID- 11007864
TI - Successful treatment of MRSA endocarditis in a haemodialysis patient.
PMID- 11007865
TI - Coinfection with leprosy and tuberculosis in a renal transplant recipient.
PMID- 11007866
TI - Tacrolimus/itraconazole interactions: a case report of ABO-incompatible living
related renal transplantation.
PMID- 11007867
TI - Renal transplantation in a patient with Barraquer-Simons disease and
mesangiocapillary glomerulonephritis type II.
PMID- 11007868
TI - Active hair bundle motion linked to fast transducer adaptation in auditory hair
cells.
AB - During transduction in auditory hair cells, hair bundle deflection opens
mechanotransducer channels that subsequently reclose or adapt to maintained
stimuli, a major component of the adaptation occurring on a submillisecond time
scale. Using a photodiode imaging technique, we measured hair bundle motion in
voltage-clamped turtle hair cells to search for a mechanical correlate of fast
adaptation. Excitatory force steps imposed by a flexible glass fiber attached to
the bundle caused an initial movement toward the kinocilium, followed by a fast
recoil equivalent to bundle stiffening. The recoil had a time course identical to
adaptation of the transducer current, and like adaptation, was most prominent for
small stimuli, was slowed by reducing extracellular calcium, and varied with hair
cell resonant frequency. In free-standing hair bundles, depolarizations positive
to 0 mV evoked an outward current attributable to opening of transducer channels,
which was accompanied by a sustained bundle deflection toward the kinocilium.
Both processes were sensitive to external calcium concentration and were
abolished by blocking the transducer channels with dihydrostreptomycin. The
similarity in properties of fast adaptation and the associated bundle motion
indicates the operation of a rapid calcium-sensitive force generator linked to
the gating of the transducer channels. This force generator may permit stimulus
amplification during transduction in auditory hair cells.
PMID- 11007869
TI - Selective regulation of N-type Ca channels by different combinations of G-protein
beta/gamma subunits and RGS proteins.
AB - We examined the effects of G-protein beta and gamma subunit heterodimers on human
alpha(1B) (N-type) Ca channels expressed in HEK293 cells. All of the known beta
subunits (beta1-beta5) produced voltage-dependent inhibition of alpha(1B) Ca
channels, depending on the gamma subunit found in the heterodimer. beta1-beta4
subunits inhibited Ca channels when paired with gamma1-gamma3. However, beta5
subunits only produced inhibition when paired with gamma2. In contrast,
heterodimers between beta5 subunits and RGS (regulators of G-protein signaling)
proteins containing GGL domains did not produce inhibition of Ca channels.
However, GGL domain-containing RGS proteins (e.g., RGS6 and RGS11) did block the
ability of Gbeta5/gamma2 heterodimers to inhibit Ca channels. Because all of the
G-protein beta subunits are found in the nervous system, we conclude that they
may all potentially participate in Ca channel inhibition. The interaction of GGL
containing RGS proteins with Gbeta5gamma2 suggests a novel way in which Ca
channels can be regulated.
PMID- 11007870
TI - Pigment epithelium-derived factor supports normal development of photoreceptor
neurons and opsin expression after retinal pigment epithelium removal.
AB - Dysfunction of the retinal pigment epithelium (RPE), its loss, or separation from
the underlying neural retina results in severe photoreceptor degeneration.
Pigment epithelium-derived factor (PEDF) is a glycoprotein with reported
neuroprotective and differentiation properties that is secreted in abundance by
RPE cells. The "pooling" of PEDF within the interphotoreceptor matrix places this
molecule in a prime physical location to affect the underlying neural retina. The
purpose of this study was to analyze the morphogenetic activity of PEDF in a
model of photoreceptor dysmorphogenesis induced by removal of the RPE. Eyes were
dissected from embryonic Xenopus laevis, and the RPE was removed before culturing
in medium containing PEDF, PEDF plus anti-PEDF antibodies, or medium alone.
Control retinas were maintained with an adherent RPE. Light and electron
microscopic analysis was used to examine retinal ultrastructure. Opsin was
localized immunocytochemically and quantified as an index of outer segment
membranous material and photoreceptor protein expression. Removal of the RPE
resulted in an aberrant assembly of photoreceptor outer segments, loss of fine
subcellular ultrastructure in photoreceptors, and a reduction in opsin protein
levels when compared with control retinas. The addition of PEDF prevented the
dysmorphic photoreceptor changes induced by RPE removal. In particular,
photoreceptor ultrastructure, outer segment membrane assembly, and steady-state
levels of opsin were equivalent to control conditions. Anti-PEDF antibodies
completely blocked the morphogenetic activity of PEDF. These results indicate
that PEDF is able to mimic the supportive role of the RPE on photoreceptors
during the final stages of retinal morphogenesis.
PMID- 11007871
TI - AMPA receptor current density, not desensitization, predicts selective motoneuron
vulnerability.
AB - Spinal motoneurons are more susceptible to AMPA receptor-mediated injury than are
other spinal neurons, a property that has been implicated in their selective
degeneration in amyotrophic lateral sclerosis (ALS). The aim of this study was to
determine whether this difference in vulnerability between motoneurons and other
spinal neurons can be attributed to a difference in AMPA receptor desensitization
and/or to a difference in density of functional AMPA receptors. Spinal
motoneurons and dorsal horn neurons were isolated from embryonic rats and
cultured on spinal astrocytes. Single-cell RT-PCR quantification of the relative
abundance of the flip and flop isoforms of the AMPA receptor subunits, which are
known to affect receptor desensitization, did not reveal any difference between
the two cell populations. Examination of AMPA receptor desensitization by patch
clamp electrophysiological measurements on nucleated and outside-out patches and
in the whole-cell mode also yielded similar results for the two cell groups.
However, AMPA receptor current density was two- to threefold higher in
motoneurons than in dorsal horn neurons, suggesting a higher density of
functional AMPA receptors in motoneuron membranes. Pharmacological reduction of
AMPA receptor current density in motoneurons to the level found in dorsal horn
neurons eliminated selective motoneuron vulnerability to AMPA receptor
activation. These results suggest that the greater AMPA receptor current density
of spinal motoneurons may be sufficient to account for their selective
vulnerability to AMPA receptor agonists in vitro.
PMID- 11007872
TI - Muscarinic stimulation of alpha1E Ca channels is selectively blocked by the
effector antagonist function of RGS2 and phospholipase C-beta1.
AB - Neuronal alpha1E Ca channel subunits are widely expressed in mammalian brain,
where they are thought to form R-type Ca channels. Recent studies have
demonstrated that R-type channels contribute to neurosecretion and dendritic Ca
influx, but little is known concerning their modulation. Here we show that
alpha1E channels are strongly stimulated, and only weakly inhibited, through M1
muscarinic acetylcholine receptors. Both forms of channel modulation are mediated
by pertussis toxin-insensitive G-proteins. Channel stimulation is blocked by
regulator of G-protein signaling 2 (RGS2) or the C-terminal region of
phospholipase C-beta1 (PLCbeta1ct), which have been previously shown to function
as GTPase-activating proteins for Galphaq. In contrast, RGS2 and PLCbeta1ct do
not block inhibition of alpha1E through M1 receptors. Inhibition is prevented,
however, by the C-terminal region of beta-adrenergic receptor kinase 1, which
sequesters Gbetagamma dimers. Thus, stimulation of alpha1E is mediated by a
pertussis toxin-insensitive Galpha subunit (e.g., Galphaq), whereas inhibition is
mediated by Gbetagamma. The ability of RGS2 and PLCbeta1ct to selectively block
stimulation indicates these proteins functioned primarily as effector
antagonists. In support of this interpretation, RGS2 prevented stimulation of
alpha1E with non-hydrolyzable guanosine 5'-0-(3-thiotriphosphate). We also report
strong muscarinic stimulation of rbE-II, a variant alpha1E Ca channel that is
insensitive to voltage-dependent inhibition. Our results predict that Galphaq
coupled receptors predominantly stimulate native R-type Ca channels. Receptor
mediated enhancement of R-type Ca currents may have important consequences for
neurosecretion, dendritic excitability, gene expression, or other neuronal
functions.
PMID- 11007873
TI - Low-affinity blockade of neuronal N-type Ca channels by the spider toxin omega
agatoxin-IVA.
AB - The recognition of neuronal Ca channel diversity has led to considerable efforts
to identify useful classification criteria. Here, we revisit the pharmacological
definition of P- and Q-type Ca channels, which is based on their respective high
and low sensitivity to the spider omega-agatoxin-IVA (omega-Aga-IVA), using whole
cell recordings of the Ca channel currents carried by 5 mM Ba(2+) in isolated rat
subthalamic and sympathetic neurons. In subthalamic neurons, omega-Aga-IVA (1
microM) targeted multiple Ca channels. One population was blocked with high
potency. These channels carried 50.4 +/- 3.4% (n = 5) of the control current and
showed the same inactivation kinetics and voltage-dependent high affinity for
omega-Aga-IVA as do prototypic P-type Ca channels. Other Ca channels were
targeted with weaker potency. This heterogeneous population contributed to 14.0
+/- 1.7% (n = 5) of the control current. It included N-type Ca channels as well
as high-threshold Ca channels that displayed the pharmacological signature of Q
type Ca channels but resembled P-type Ca channels in their gating properties. N
type Ca current block by omega-Aga-IVA (1 microM) was further investigated in
sympathetic neurons, which mainly express this Ca channel type. Block was
incomplete ( approximately 30% of the control current). Its relief at positive
potentials was consistent with omega-Aga-IVA acting as a channel-gating modifier.
These effects did not reflect a complete loss of selectivity, because omega-Aga
IVA (1 microM) had no effect on subthalamic Na and K currents or their T- and L
type Ca currents. Our data confirm that omega-Aga-IVA is a selective P-type Ca
channel blocker. However, its diminished selectivity in the micromolar range
limits its usefulness for functional studies of Q-type Ca channels.
PMID- 11007874
TI - Transient NMDA receptor inactivation provides long-term protection to cultured
cortical neurons from a variety of death signals.
AB - NMDA receptor antagonists, such as (+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]
cyclohepten-5,10-imine maleate (MK-801), potently block glutamate-induced
neuronal death in myriad in vitro cell models and effectively attenuate ischemic
damage in vivo. In this report, a novel role for MK-801 and other NMDA receptor
antagonists in preconditioning neurons to withstand a wide range of subsequent
lethal insults is described. A brief 30 min exposure to 0.1 microM MK-801,
applied up to 96 hr before a "lethal" insult, protected primary cortical neurons
from a diverse group of neurotoxic agents, including NMDA, beta-amyloid,
staurosporine, etoposide, and oxygen-glucose deprivation. This neuroprotective
preconditioning by MK-801 arose from transient NMDA receptor inactivation,
because the noncompetitive NMDA receptor antagonists memantine and nylindin and
the competitive antagonist AP-5 gave similar effects. MK-801 protection was
dependent on new protein synthesis during the first 2 hr, but not from 2 to 5 hr,
after MK-801 exposure. The MK-801 transient did not alter the ability of NMDA to
trigger normally lethal [Ca(2+)](i) influx 48 hr later, but it did block early
downstream signaling events coupled to NMDA neurotoxicity, including PKC
inactivation and the activation of calpain. Moreover, MK-801 protected neurons
from staurosporine-induced apoptosis, although caspase activation in these cells
was unimpeded. It is likely that the stress associated with transient
inactivation of NMDA receptors triggered a rapid compensatory survival response
that provided long-term protection from a spectrum of insults, inducing apoptotic
and nonapoptotic death. The possibility that MK-801 preconditioning blocks an
event common to seemingly diverse death mechanisms suggests it will be an
important tool for obtaining a clearer understanding of the salient molecular
events at work in neuronal death and survival pathways.
PMID- 11007875
TI - Coordinated gating of TRP-dependent channels in rhabdomeral membranes from
Drosophila retinas.
AB - Using a newly developed dissociation procedure, we isolated the specialized
rhabdomeral membranes from Drosophila retinal photoreceptors. From these
membranes, we have recorded spontaneous active currents in excised patch, voltage
clamp recordings. We observed rapid opening events that closely resembled those
ascribed to one class of light-activated channels, TRP. All activity exhibited
Ba(2+) permeability, little voltage dependence, and sensitivity to La(3+) block.
Mutational analysis indicated that the spontaneous activity present in these
membranes was TRP-dependent. Excised patches from wild-type rhabdomeral membranes
exhibited a wide range of conductance amplitudes. In addition, large conductance
events exhibited many conductance levels in the open state. Block of activity by
La(3+) both developed and recovered in a stepwise manner. Our results indicate
that TRP-dependent channels have a small unitary conductance and that many
channels can be gated coordinately.
PMID- 11007876
TI - Protein phosphatase-mediated regulation of protein kinase C during long-term
depression in the adult hippocampus in vivo.
AB - The neural substrates of learning and memory are thought to involve use-dependent
long-term changes in synaptic function, including long-term depression (LTD) of
synaptic strength. One biochemical event hypothesized to contribute to the
maintenance and expression of LTD is decreased protein phosphorylation, caused by
a decrease in protein kinase activity and/or an increase in protein phosphatase
activity. We tested whether the activity of protein kinase C (PKC) decreases
after the induction of LTD in area CA1 of the adult hippocampus in vivo, and then
investigated the mechanism responsible for the LTD-associated alteration in PKC
activity. We found that LTD was associated with a significant decrease in both
autonomous and cofactor-dependent PKC activity. The decrease in PKC activity was
prevented by NMDA receptor blockade and was not accompanied by a decrease in the
level of either PKCalpha, beta, gamma, or zeta. Western blot analysis with
phosphospecific antibodies revealed that phosphorylation of Ser-657 on the
catalytic domain of PKCalpha (Ser-660 on PKCbetaII) was decreased significantly
after the induction of LTD, and that this dephosphorylation was prevented by the
protein phosphatase inhibitor okadaic acid. The decrease in autonomous and
cofactor-dependent PKC activity likewise was prevented by okadaic acid. These
findings suggest that LTD in the adult hippocampus in vivo involves a decrease in
PKC activity that is mediated, at least in part, by dephosphorylation of the
catalytic domain of PKC by protein phosphatases activated after LTD-inducing
stimulation. Our findings are consistent with the idea that protein
dephosphorylation contributes to the expression of LTD.
PMID- 11007877
TI - Mitochondrial membrane potential and glutamate excitotoxicity in cultured
cerebellar granule cells.
AB - The relationship between changes in mitochondrial membrane potential
(Deltapsi(m)) and the failure of cytoplasmic Ca(2+) homeostasis, delayed
Ca(2+)deregulation (DCD), is investigated for cultured rat cerebellar granule
cells exposed to glutamate. To interpret the single-cell fluorescence response of
cells loaded with tetramethylrhodamine methyl ester (TMRM(+)) or rhodamine-123,
we devised and validated a mathematical simulation with well characterized
effectors of Deltapsi(m) and plasma membrane potential (Deltapsi(P)). Glutamate
usually caused an immediate decrease in Deltapsi(m) of <10 mV, attributable to
Ca(2+) accumulation rather than enhanced ATP demand, and these cells continued to
generate ATP by oxidative phosphorylation until DCD. Cells for which the
mitochondria showed a larger initial depolarization deregulated more rapidly. The
mitochondria in a subpopulation of glutamate-exposed cells that failed to extrude
Ca(2+) that was released from the matrix after protonophore addition were
bioenergetically competent. The onset of DCD during continuous glutamate exposure
in the presence or absence of oligomycin was associated with a slowly developing
mitochondrial depolarization, but cause and effect could not be established
readily. In contrast, the slowly developing mitochondrial depolarization after
transient NMDA receptor activation occurs before cytoplasmic free Ca(2+)
([Ca(2+)](c)) has risen to the set point at which mitochondria retain Ca(2+). In
the presence of oligomycin no increase in [Ca(2+)](c) occurs during this
depolarization. We conclude that transient Ca(2+) loading of mitochondria as a
consequence of NMDA receptor activation initiates oxidative damage to both plasma
membrane Ca(2+) extrusion pathways and the inhibition of mitochondrial
respiration. Depending on experimental conditions, one of these factors becomes
rate-limiting and precipitates DCD.
PMID- 11007878
TI - Potentiation of a voltage-gated proton current in acidosis-induced swelling of
rat microglia.
AB - Microglia are equipped with a strong proton (H(+)) extrusion pathway, a voltage
gated H(+) channel, probably to compensate for the large amount of H(+) generated
during phagocytosis; however, little is known about how this channel is regulated
in pathological states. Because neural damage is often associated with
intracellular and extracellular acidosis, we examined the regulatory mechanisms
of the H(+) current of rat spinal microglia in acidic environments. More than 90%
of round/amoeboid microglia expressed the H(+) current, which was characterized
by slow activation kinetics, dependencies on both intracellular and extracellular
pH, and blockage by Zn(2+). Extracellular lactoacidosis, pH 6.8, induced
intracellular acidification and cell swelling. Cell swelling was also induced by
intracellular dialysis with acidic pipette solutions, pH 5.5-6.8, at normal
extracellular pH 7.3 in the presence of Na(+). The H(+) currents were increased
in association with cell swelling as shown by shifts of the half-activation
voltage to more negative potentials and by acceleration of the activation
kinetics. The acidosis-induced cell swelling and the accompanying potentiation of
the H(+) current required nonhydrolytic actions of intracellular ATP and were
inhibited by agents affecting actin filaments (phalloidin and cytochalasin D).
The H(+) current was also potentiated by swelling caused by hypotonic stress.
These findings suggest that the H(+) channel of microglia can be potentiated via
cell swelling induced by intracellular acidification. This potentiation might
operate as a negative feedback mechanism to protect microglia from cytotoxic
acidification and hence acidosis-induced swelling in pathological states of the
CNS.
PMID- 11007879
TI - Phosphatidylinositol 3-kinase is required for the trophic, but not the survival
promoting, actions of NGF on sympathetic neurons.
AB - Nerve growth factor (NGF) supports target-dependent survival of sympathetic and
other neurons during development; however, the NGF-regulated signaling pathways
required for survival are not fully understood. Sympathetic neurons are able to
abort acutely the cell death pathway initiated by NGF deprivation at early, as
well as late, time points after readdition of NGF. We found that NGF-dependent
phosphatidylinositol 3-kinase (PI-3-K) activity inhibited an early cell death
event proximal to c-Jun phosphorylation. However, PI-3-K activity was not
required for NGF to inhibit the translocation of Bax from the cytoplasm to the
mitochondria, nor was it required for NGF to inhibit the subsequent release of
mitochondrial cytochrome c, two events required for NGF deprivation-induced
apoptosis. MEK/MAPK activity did not account for any of these NGF-dependent
events. When subjected to long-term PI-3-K inhibition in the presence of NGF, the
majority of sympathetic neurons did not die. Those that did die exhibited
significant differences in the characteristics of death caused by PI-3-K
inhibition as compared with NGF deprivation. Additionally, PI-3-K inhibition in
the presence of NGF did not induce release of mitochondrial cytochrome c,
indicating that these neurons were unable to complete the apoptotic program. In
contrast to its modest effects on survival, inhibition of PI-3-K induced marked
decreases in somal diameter and metabolic function, as measured by 3-(4,5
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, suggesting
that PI-3-K is required for the trophic effects of NGF. Therefore, although PI-3
K is important for the trophic effects of NGF, it is not required for survival.
Other, or at least additional, signaling pathways contribute to NGF-mediated
survival of sympathetic neurons.
PMID- 11007880
TI - Homer proteins regulate coupling of group I metabotropic glutamate receptors to N
type calcium and M-type potassium channels.
AB - Group I metabotropic glutamate receptors (mGluR1 and 5) couple to intracellular
calcium pools by a family of proteins, termed Homer, that cross-link the receptor
to inositol trisphosphate receptors. mGluRs also couple to membrane ion channels
via G-proteins. The role of Homer proteins in channel modulation was investigated
by expressing mGluRs and various forms of Homer in rat superior cervical ganglion
(SCG) sympathetic neurons by intranuclear cDNA injection. Expression of cross
linking-capable forms of Homer (Homer 1b, 1c, 2, and 3, termed long forms)
occluded group I mGluR-mediated N-type calcium and M-type potassium current
modulation. This effect was specific for group I mGluRs. mGluR2 (group II)
mediated inhibition of N-channels was unaltered. Long forms of Homer decreased
modulation of N- and M-type currents but did not selectively block distinct G
protein pathways. Short forms of Homer, which cannot self-multimerize (Homer 1a
and a Homer 2 C-terminal deletion), did not alter mGluR-ion channel coupling.
When coexpressed with long forms of Homer, short forms restored the mGluR1a
mediated calcium current modulation in an apparent dose-dependent manner. Homer
2b induced cell surface clusters of mGluR5 in SCG neurons. Conversely, a uniform
distribution was observed when mGluR5 was expressed alone or with Homer short
forms. These studies indicate that long and short forms of Homer compete for
binding to mGluRs and regulate their coupling to ion channels. In vivo, the
immediate early Homer 1a is anticipated to enhance ion channel modulation and to
disrupt coupling to releasable intracellular calcium pools. Thus, Homer may
regulate the magnitude and predominate signaling output of group I mGluRs.
PMID- 11007881
TI - Calcineurin-mediated BAD dephosphorylation activates the caspase-3 apoptotic
cascade in traumatic spinal cord injury.
AB - We report here that activation of the caspase-3 apoptotic cascade in spinal cord
injury is regulated, in part, by calcineurin-mediated BAD dephosphorylation. BAD,
a proapoptotic member of the bcl-2 gene family, is rapidly dephosphorylated after
injury, dissociates from 14-3-3 in the cytosol, and translocates to the
mitochondria of neurons where it binds to Bcl-x(L). Pretreatment of animals with
FK506, a potent inhibitor of calcineurin activity, or MK801, an NMDA glutamate
receptor antagonist, blocked BAD dephosphorylation and abolished activation of
the caspase-3 apoptotic cascade. These findings extend previous in vitro
observations and are the first to implicate the involvement of glutamate-mediated
calcineurin activation and BAD dephosphorylation as upstream, premitochondrial
signaling events leading to caspase-3 activation in traumatic spinal cord injury.
PMID- 11007882
TI - PICK1 interacts with and regulates PKC phosphorylation of mGLUR7.
AB - The G-protein-coupled metabotropic glutamate receptor subtype 7a (mGluR7a) is a
member of group III metabotropic glutamate receptors that plays an important role
as a presynaptic receptor in regulating transmitter release at glutamatergic
synapses. Here we report that the protein interacting with C-kinase (PICK1) binds
to the C terminus (ct) of mGluR7a. In the yeast two-hybrid system, the extreme ct
of mGluR7a was shown to interact with the PSD-95/Discs large/ZO-1 (PDZ) domain of
PICK1. Pull-down assays indicated that PICK1 was retained by a glutathione S
transferase fusion of ct-mGluR7a. Furthermore, recombinant and native
PICK1/mGluR7a complexes were coimmunoprecipitated from COS-7 cells and rat brain
tissue, respectively. Confocal microscopy showed that both PICK1 and mGluR7a
displayed synaptic colocalization in cultured hippocampal neurons. PICK1 has
previously been shown to bind protein kinase C alpha-subunit (PKCalpha), and
mGluR7a is known to be phosphorylated by PKC. We show a relationship between
these three proteins using recombinant PICK1, mGluR7, and PKCalpha, where they
were co-immunoprecipitated as a complex from COS-7 cells. In addition, PICK1
caused a reduction in PKCalpha-evoked phosphorylation of mGluR7a in in vitro
phosphorylation assays. These results suggest a role for PICK1 in modulating
PKCalpha-evoked phosphorylation of mGluR7a.
PMID- 11007883
TI - Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its
interaction with PDZ domain-containing proteins.
AB - PSD-95, DLG, ZO-1 (PDZ) domain-mediated protein interactions have been shown to
play important roles in the regulation of glutamate receptor function at
excitatory synapses. Recent studies demonstrating the rapid regulation of AMPA
receptor function during synaptic plasticity have suggested that AMPA receptor
interaction with PDZ domain-containing proteins may be dynamically modulated.
Here we show that PKC phosphorylation of the AMPA receptor GluR2 subunit
differentially modulates its interaction with the PDZ domain-containing proteins
GRIP1 and PICK1. The serine residue [serine-880 (Ser880)] in the GluR2 C-terminal
sequence (IESVKI) critical for PDZ domain binding is a substrate of PKC and is
phosphorylated in vivo. In vitro binding and coimmunoprecipitation studies show
that phosphorylation of serine-880 within the GluR2 PDZ ligand significantly
decreases GluR2 binding to GRIP1 but not to PICK1. Immunostaining of cultured
hippocampal neurons demonstrates that the Ser880-phosphorylated GluR2 subunits
are enriched and colocalized with PICK1 in the dendrites, with very little
staining observed at excitatory synapses. Interestingly, PKC activation in
neurons increases the Ser880 phosphorylation of GluR2 subunits and recruits PICK1
to excitatory synapses. Moreover, PKC stimulation in neurons results in rapid
internalization of surface GluR2 subunits. These results suggest that GluR2
phosphorylation of serine-880 may be important in the regulation of the AMPA
receptor internalization during synaptic plasticity.
PMID- 11007884
TI - Huntingtin expression stimulates endosomal-lysosomal activity, endosome
tubulation, and autophagy.
AB - An expansion of polyglutamines in the N terminus of huntingtin causes
Huntington's disease (HD) and results in the accrual of mutant protein in the
nucleus and cytoplasm of affected neurons. How mutant huntingtin causes neurons
to die is unclear, but some recent observations suggest that an autophagic
process may occur. We showed previously that huntingtin markedly accumulates in
endosomal-lysosomal organelles of affected HD neurons and, when exogenously
expressed in clonal striatal neurons, huntingtin appears in cytoplasmic vacuoles
causing cells to shrink. Here we show that the huntingtin-enriched cytoplasmic
vacuoles formed in vitro internalized the lysosomal enzyme cathepsin D in
proportion to the polyglutamine-length in huntingtin. Huntingtin-labeled vacuoles
displayed the ultrastructural features of early and late autophagosomes
(autolysosomes), had little or no overlap with ubiquitin, proteasome, and heat
shock protein 70/heat shock cognate 70 immunoreactivities, and altered the
arrangement of Golgi membranes, mitochondria, and nuclear membranes. Neurons with
excess cytoplasmic huntingtin also exhibited increased tubulation of endosomal
membranes. Exogenously expressed human full-length wild-type and mutant
huntingtin codistributed with endogenous mouse huntingtin in soluble and membrane
fractions, whereas human N-terminal huntingtin products were found only in
membrane fractions that contained lysosomal organelles. We speculate that mutant
huntingtin accumulation in HD activates the endosomal-lysosomal system, which
contributes to huntingtin proteolysis and to an autophagic process of cell death.
PMID- 11007885
TI - Changes in expression of two tetrodotoxin-resistant sodium channels and their
currents in dorsal root ganglion neurons after sciatic nerve injury but not
rhizotomy.
AB - Two TTX-resistant sodium channels, SNS and NaN, are preferentially expressed in c
type dorsal root ganglion (DRG) neurons and have been shown recently to have
distinct electrophysiological signatures, SNS producing a slowly inactivating and
NaN producing a persistent sodium current with a relatively hyperpolarized
voltage-dependence. An attenuation of SNS and NaN transcripts has been
demonstrated in small DRG neurons after transection of the sciatic nerve.
However, it is not known whether changes in the currents associated with SNS and
NaN or in the expression of SNS and NaN channel protein occur after axotomy of
the peripheral projections of DRG neurons or whether similar changes occur after
transection of the central (dorsal root) projections of DRG neurons. Peripheral
and central projections of L4/5 DRG neurons in adult rats were axotomized by
transection of the sciatic nerve and the L4 and L5 dorsal roots, respectively.
DRG neurons were examined using immunocytochemical and patch-clamp methods 9-12 d
after sciatic nerve or dorsal root lesion. Levels of SNS and NaN protein in the
two types of injuries were paralleled by their respective TTX-resistant currents.
There was a significant decrease in SNS and NaN signal intensity in small DRG
neurons after peripheral, but not central, axotomy compared with control neurons.
Likewise, there was a significant reduction in slowly inactivating and persistent
TTX-resistant currents in these neurons after peripheral, but not central,
axotomy compared with control neurons. These results indicate that peripheral,
but not central, axotomy results in a reduction in expression of functional SNS
and NaN channels in c-type DRG neurons and suggest a basis for the altered
electrical properties that are observed after peripheral nerve injury.
PMID- 11007886
TI - Stimulation-evoked increases in cytosolic [Ca(2+)] in mouse motor nerve terminals
are limited by mitochondrial uptake and are temperature-dependent.
AB - Increases in cytosolic [Ca(2+)] evoked by trains of action potentials (20-100 Hz)
were recorded from mouse and lizard motor nerve terminals filled with a low
affinity fluorescent indicator, Oregon Green BAPTA 5N. In mouse terminals at near
physiological temperatures (30-38 degrees C), trains of action potentials at 25
100 Hz elicited increases in cytosolic [Ca(2+)] that stabilized at plateau levels
that increased with stimulation frequency. Depolarization of mitochondria with
carbonylcyanide m-chlorophenylhydrazone (CCCP) or antimycin A1 caused cytosolic
[Ca(2+)] to rise to much higher levels during stimulation. Thus, mitochondrial
Ca(2+) uptake contributes importantly to limiting the rise of cytosolic [Ca(2+)]
during repetitive stimulation. In mouse terminals, the stimulation-induced
increase in cytosolic [Ca(2+)] was highly temperature-dependent over the range 18
38 degrees C, with greater increases at lower temperatures. At the lower
temperatures, application of CCCP continued to depolarize mitochondria but
produced a much smaller increase in the cytosolic [Ca(2+)] transient evoked by
repetitive stimulation. This result suggests that the larger amplitude of the
stimulation-induced cytosolic [Ca(2+)] transient at lower temperatures was
attributable in part to reduced mitochondrial Ca(2+) uptake. In contrast, the
stimulation-induced increases in cytosolic [Ca(2+)] measured in lizard motor
terminals showed little or no temperature-dependence over the range 18-33 degrees
C.
PMID- 11007887
TI - Synaptic vesicle transporter expression regulates vesicle phenotype and quantal
size.
AB - While the transporters that accumulate classical neurotransmitters in synaptic
vesicles have been identified, little is known about how their expression
regulates synaptic transmission. We have used adenoviral-mediated transfection to
increase expression of the brain vesicular monoamine transporter VMAT2 and
presynaptic amperometric recordings to characterize the effects on quantal
release. In presynaptic axonal varicosities of ventral midbrain neurons in
postnatal culture, VMAT2 overexpression in small synaptic vesicles increased both
quantal size and frequency, consistent with the recruitment of synaptic vesicles
that do not normally release dopamine. This was confirmed using
noncatecholaminergic AtT-20 cells, in which VMAT2 expression induced the quantal
release of dopamine. The ability to increase quantal size in vesicles that were
already competent for dopamine release was shown in PC12 cells, in which VMAT2
expression increased the quantal size but not the number of release events. These
results demonstrate that vesicle transporters limit the rate of transmitter
accumulation and can alter synaptic strength through two distinct mechanisms.
PMID- 11007888
TI - GluR3 autoantibodies destroy neural cells in a complement-dependent manner
modulated by complement regulatory proteins.
AB - GluR3 autoantibodies have been implicated in the development of Rasmussen's
encephalitis, a rare neurodegenerative disease of humans characterized by
epilepsy and degeneration of a single cerebral hemisphere. GluR3 autoantibodies
are found in some Rasmussen's encephalitis patients, and GluR3 antibodies raised
in rabbits destroy cultured cortical cells in a complement-dependent manner. In
this study, the cellular targets of anti-GluR3 antisera-mediated cytotoxicity
were examined in mixed primary neuronal-glial cultures of rat cortex.
Unexpectedly, astrocytes were the principal target of the cytotoxic effects as
assessed by immunohistochemistry and lactate dehydrogenase activity; neurons were
destroyed to a lesser extent. Astrocyte vulnerability was rescued by transfection
with complement regulatory proteins, and neuronal resistance was defeated by
impairing complement regulatory protein function. Astrocyte death may occur in
Rasmussen's encephalitis, and destruction of this cell type may play a critical
role in the progression of this disorder. The present findings suggest complement
regulatory protein expression may in part determine the nature and severity of
Rasmussen's encephalitis and other complement-dependent nervous system diseases
and thus underscore the need for a systematic investigation of the expression of
all known complement regulatory proteins in healthy and diseased nervous system
tissues.
PMID- 11007889
TI - The architectural transcription factor high mobility group I(Y) participates in
photoreceptor-specific gene expression.
AB - The nonhistone chromosomal proteins high mobility group I(Y) [HMG I(Y)] have been
shown to function as architectural transcription factors facilitating
enhanceosome formation on a variety of mammalian promoters. Specifically, they
have been shown to act as a "molecular glue" mediating protein-protein and
protein-DNA contacts within the enhanceosome complex. HMG I(Y) proteins are
expressed at high levels in embryonic and transformed cells and have been
implicated in transcriptional regulation in these cells. Terminally
differentiated cells, however, have been reported to express only minimal, if
any, HMG I(Y). In contrast to these observations, we show here that adult mouse
retinal photoreceptors, which are terminally differentiated cells, express high
levels of these proteins. Using retinoblastoma cells as an approximate model, we
further demonstrate in transiently transfected cells that inhibition of HMG I(Y)
expression and mutation of HMG I(Y) binding sites significantly reduce rhodopsin
promoter activity. DNase I footprint analysis indicates that HMG I protein
interacts with a discrete site within the rhodopsin proximal promoter. This site
overlaps with the binding site for Crx, a paired-like homeodomain transcription
factor that is essential for photoreceptor functioning and that when mutated
causes several forms of human photoreceptor degeneration. Both biochemical and
functional experiments demonstrate that HMG I(Y) physically associate with Crx
and that their interaction with DNA is required for high-level transcription of
the rhodopsin gene. These data provide the first demonstration that HMG I(Y) can
be important for gene activation in terminally differentiated cells.
PMID- 11007890
TI - NGF signals through TrkA to increase clathrin at the plasma membrane and enhance
clathrin-mediated membrane trafficking.
AB - Neurotrophin (NT) signals may be moved from axon terminals to neuron cell bodies
via signaling endosomes-organelles in which NTs continue to be bound to their
activated receptors. Suggesting that clathrin-coated membranes serve as one
source of signaling endosomes, in earlier studies we showed that nerve growth
factor (NGF) treatment increased clathrin at the plasma membrane and resulted in
colocalization of clathrin with TrkA, the receptor tyrosine kinase for NGF.
Strikingly, however, we also noted that most clathrin puncta at the surface of
NGF-treated cells did not colocalize with TrkA, raising the possibility that NGF
induces a general increase in clathrin-coated membrane formation. To explore this
possibility further, we examined the distribution of clathrin in NGF- and BDNF
treated cells. NGF signaling in PC12 cells robustly redistributed the adaptor
protein AP2 and the clathrin heavy chain (CHC) to surface membranes. Using
confocal and epifluorescence microscopy, as well as biochemical assays, we showed
the redistribution of clathrin to be attributable to the activation of TrkA.
Significantly, NGF signaled through TrkA to induce an increase in clathrin
mediated membrane trafficking, as revealed in the increased endocytosis of
transferrin. In that BDNF treatment increased AP2 and clathrin at the surface
membranes of hippocampal neurons, these findings may represent a physiologically
significant response to NTs. We conclude that NT signaling increases clathrin
coated membrane formation and clathrin-mediated membrane trafficking and
speculate that this effect contributes to their trophic actions via the increased
internalization of receptors and other proteins that are present in clathrin
coated membranes.
PMID- 11007891
TI - Biogenesis of regulated exocytotic carriers in neuroendocrine cells.
AB - Ca(2+)-triggered exocytosis is a hallmark of neurosecretory granules, but the
cellular pathway leading to the assembly of these regulated exocytotic carriers
is poorly understood. Here we used the pituitary AtT-20 cell line to study the
biogenesis of regulated exocytotic carriers involved in peptide hormone
secretion. We show that immature secretory granules (ISGs) freshly budded from
the trans-Golgi network (TGN) exhibit characteristics of unregulated exocytotic
carriers. During a subsequent maturation period they undergo an important switch
to become regulated exocytotic carriers. We have identified a novel sorting
pathway responsible for this transition. The SNARE proteins, VAMP4 and
synaptotagmin IV (Syt IV), enter ISGs initially but are sorted away during
maturation. Sorting is achieved by vesicle budding from the ISGs, because it can
be inhibited by brefeldin A (BFA). Inhibition of this sorting pathway with BFA
arrested the maturing granules in a state that responded poorly to stimuli,
suggesting that the transition to regulated exocytotic carriers requires the
removal of a putative inhibitor. In support of this, we found that overexpression
of Syt IV reduced the stimulus-responsiveness of maturing granules. We conclude
that secretory granules undergo a switch from unregulated to regulated secretory
carriers during biogenesis. The existence of such a switch may provide a
mechanism for cells to modulate their secretory activities under different
physiological conditions.
PMID- 11007892
TI - The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's
disease-associated neurodegeneration and oxidative stress.
AB - In Alzheimer's disease (AD) brains, selected populations of neurons degenerate
heavily, whereas others are frequently spared from degeneration. To address the
cellular basis for this selective vulnerability of neurons in distinct brain
regions, we compared gene expression between the severely affected inferior
temporal lobes and the mostly unaffected fronto-parietal cortices by using an
mRNA differential display. We identified seladin-1, a novel gene, which was
downregulated in large pyramidal neurons in vulnerable regions in AD but not
control brains. Seladin-1 is a human homolog of the DIMINUTO/DWARF1 gene
described in plants and Caenorhabditis elegans. Its sequence shares similarities
with flavin-adenin-dinucleotide (FAD)-dependent oxidoreductases. In human control
brain, seladin-1 was highly expressed in almost all neurons. In PC12 cell clones
that were selected for resistance against AD-associated amyloid-beta peptide
(Abeta)-induced toxicity, both mRNA and protein levels of seladin-1 were
approximately threefold higher as compared with the non-resistant wild-type
cells. Functional expression of seladin-1 in human neuroglioma H4 cells resulted
in the inhibition of caspase 3 activation after either Abeta-mediated toxicity or
oxidative stress and protected the cells from apoptotic cell death. In apoptotic
cells, however, endogenous seladin-1 was cleaved to a 40 kDa derivative in a
caspase-dependent manner. These results establish that seladin-1 is an important
factor for the protection of cells against Abeta toxicity and oxidative stress,
and they suggest that seladin-1 may be involved in the regulation of cell
survival and death. Decreased expression of seladin-1 in specific neurons may be
a cause for selective vulnerability in AD.
PMID- 11007893
TI - Mechanisms mediating pituitary adenylate cyclase-activating polypeptide
depolarization of rat sympathetic neurons.
AB - The direct effects of pituitary adenylate cyclase-activating polypeptides (PACAP)
on sympathetic neurons were investigated using rat superior cervical ganglion
neurons. Electrophysiological and pharmacological analyses were used to evaluate
PACAP modulation of sympathetic neuron membrane potentials and to investigate
potential ionic and intracellular signaling mechanisms mediating the responses.
More than 90% of the sympathetic neurons were depolarized by the PACAP peptides
even when stimulated release was blocked, indicating that the PACAP peptides
elicited primary responses in the postganglionic neurons. The response profile
was consistent for activation of PACAP-selective PAC(1) receptors: nanomolar
concentrations of PACAP27 and PACAP38 were required to stimulate depolarization,
whereas vasoactive intestinal peptide failed to evoke any response. Furthermore,
depolarizations elicited by PACAP27 were reduced by the PAC(1) receptor
antagonist PACAP(6-38). Both sodium influx and inhibition of a potassium current
contributed to the peptide-induced depolarizations. Activation of neither
pertussis toxin- nor cholera toxin-sensitive G-proteins was required for
generation of the depolarizations. cAMP and diacylglycerol production and
activation of protein kinase A or protein kinase C also were not requisite for
the responses. By contrast, phospholipase C (PLC)-dependent inositol 1,4,5
triphosphate (IP(3)) synthesis was crucial to the PACAP-mediated depolarizations.
Although calcium release from IP(3)-sensitive stores was not required for the
PACAP-induced responses, inhibition of IP(3) receptors reduced the
depolarizations. Thus, among the many signal transduction pathways coupled to the
PAC(1) receptor, the PACAP-induced depolarization of sympathetic neurons appears
to require activation of PLC and subsequent generation of IP(3).
PMID- 11007894
TI - Catecholamines are required for the acquisition of secretory responsiveness by
sweat glands.
AB - The sympathetic innervation of sweat glands undergoes a developmental change in
transmitter phenotype from catecholaminergic to cholinergic. Acetylcholine
elicits sweating and is necessary for development and maintenance of secretory
responsiveness, the ability of glands to produce sweat after nerve stimulation or
agonist administration. To determine whether catecholamines play a role in the
development or function of this system, we examined the onset of secretory
responsiveness in two transgenic mouse lines, one albino and the other pigmented,
that lack tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine
synthesis. Although both lines lack TH, their catecholamine levels differ because
tyrosinase in pigmented mice serves as an alternative source for catecholamine
synthesis (Rios et al., 1999). At postnatal day 21 (P21), 28 glands on average
are active in interdigital hind footpads of albino TH wild-type mice. In
contrast, fewer than one gland is active in albino TH null mice, which lack
catecholamines in gland innervation. Treatment of albino TH null mice with DOPA,
a catecholamine precursor, from P11 to P21 increases the number of active glands
to 14. Pigmented TH null mice, which have faint catecholamine fluorescence in the
developing gland innervation, possess 12 active glands at P21, indicating that
catecholamines made via tyrosinase, albeit reduced from wild-type levels, support
development of responsiveness. Gland formation and the appearance of cholinergic
markers occur normally in albino TH null mice, suggesting that catecholamines act
directly on gland cells to trigger their final differentiation and to induce
responsiveness. Thus, catecholamines, like acetylcholine, are essential for the
development of secretory responsiveness.
PMID- 11007895
TI - Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal
differentiation by isolated neural crest stem cells.
AB - Isolated neural crest stem cells (NCSCs) differentiate to autonomic neurons in
response to bone morphogenetic protein 2 (BMP2) in clonal cultures, but these
neurons do not express sympathoadrenal (SA) lineage markers. Whether this
reflects a developmental restriction in NCSCs or simply inappropriate culture
conditions was not clear. We tested the growth and differentiation potential of
NCSCs at approximately 5% O(2), which more closely approximates physiological
oxygen levels. Eighty-three percent of p75(+)P(0-) cells isolated from embryonic
day 14.5 sciatic nerve behaved as stem cells under these conditions, suggesting
that this is a nearly pure population. Furthermore, addition of BMP2 plus
forskolin in decreased oxygen cultures elicited differentiation of thousands of
cells expressing tyrosine hydroxylase, dopamine-beta-hydroxylase, and the SA
lineage marker SA-1 in nearly all colonies. Such cells also synthesized and
released dopamine and norepinephrine. These data demonstrate that isolated
mammalian NCSCs uniformly possess SA lineage capacity and further suggest that
oxygen levels can influence cell fate. Parallel results indicating that reduced
oxygen levels can also promote the survival, proliferation, and catecholaminergic
differentiation of CNS stem cells (Studer et al., 2000) suggests that neural stem
cells may exhibit a conserved response to reduced oxygen levels.
PMID- 11007896
TI - Enhanced proliferation, survival, and dopaminergic differentiation of CNS
precursors in lowered oxygen.
AB - Standard cell culture systems impose environmental oxygen (O(2)) levels of 20%,
whereas actual tissue O(2) levels in both developing and adult brain are an order
of magnitude lower. To address whether proliferation and differentiation of CNS
precursors in vitro are influenced by the O(2) environment, we analyzed embryonic
day 12 rat mesencephalic precursor cells in traditional cultures with 20% O(2)
and in lowered O(2) (3 +/- 2%). Proliferation was promoted and apoptosis was
reduced when cells were grown in lowered O(2), yielding greater numbers of
precursors. The differentiation of precursor cells into neurons with specific
neurotransmitter phenotypes was also significantly altered. The percentage of
neurons of dopaminergic phenotype increased to 56% in lowered O(2) compared with
18% in 20% O(2). Together, the increases in total cell number and percentage of
dopaminergic neurons resulted in a ninefold net increase in dopamine neuron
yield. Differential gene expression analysis revealed more abundant messages for
FGF8, engrailed-1, and erythropoietin in lowered O(2). Erythropoietin
supplementation of 20% O(2) cultures partially mimicked increased dopaminergic
differentiation characteristic of CNS precursors cultured in lowered O(2). These
data demonstrate increased proliferation, reduced cell death, and enhanced
dopamine neuron generation in lowered O(2), making this method an important
advance in the ex vivo generation of specific neurons for brain repair.
PMID- 11007897
TI - Tumor necrosis factor receptor-associated factor 6 (TRAF6) deficiency results in
exencephaly and is required for apoptosis within the developing CNS.
AB - Tumor necrosis factor receptor-associated factors (TRAFs) are adaptor proteins
important in mediating intracellular signaling. We report here that targeted
deletion of traf6 greatly increases the frequency of failure of neural tube
closure and exencephaly in traf6 (-/-) mice. The penetrance of this defect is
influenced by genetic background. Neural tube fusion requires the coordination of
several biological processes, including cell migration invoked by contact
dependent signaling, cell proliferation, and programmed cell death (PCD). To gain
greater insight into the role of TRAF6 in these processes, neural development and
migration within the CNS of traf6 (-/-) mice and controls were assessed through
temporal examination of a number of immunohistochemical markers. In addition,
relative levels of cellular proliferation and PCD were examined throughout
embryonic development using bromodeoxyuridine (BrdU) and in situ terminal
deoxynucleotidyl transferase-mediated dUTP biotinylated nick end labeling
(TUNEL), respectively. The data suggest that loss of TRAF6 does not significantly
alter the level of cellular proliferation or the pattern of neural
differentiation per se, but rather regulates the level of PCD within specific
regions of the developing CNS. Substantial reductions in TUNEL were observed
within the ventral diencephalon and mesencephalon in exencephalic traf6 (-/-)
embryos. Our results demonstrate a novel and prominent role for TRAF6 in the
regional control of PCD within the developing CNS.
PMID- 11007898
TI - L-Type calcium channels mediate calcium oscillations in early postnatal Purkinje
neurons.
AB - Ca(2+) signaling is important in many fundamental neuronal processes including
neurotransmission, synaptic plasticity, neuronal development, and gene
expression. In cerebellar Purkinje neurons, Ca(2+) signaling has been studied
primarily in the dendritic region where increases in local Ca(2+) have been shown
to occur with both synaptic events and spontaneous electrical activity involving
P-type voltage-gated Ca(2+) channels (VGCCs), the predominant VGCC expressed by
Purkinje neurons. Here we show that Ca(2+) signaling is also a prominent feature
of immature Purkinje neurons at developmental stages that precede expression of
dendritic structure and involves L-type rather than P-type VGCCs. Immature
Purkinje neurons acutely dissociated from postnatal day 4-7 rat pups exhibit
spontaneous cytoplasmic Ca(2+) oscillations. The Ca(2+) oscillations require
entry of extracellular Ca(2+), are blocked by tetrodotoxin, are communicated to
the nucleus, and correlate closely with patterns of endogenously generated
spontaneous and evoked electrical activity recorded in the neurons.
Immunocytochemistry showed that L-, N-, and P/Q-types of VGCCs are present on the
somata of the Purkinje neurons at this age. However, only the L-type VGCC
antagonist nimodipine effectively antagonized the Ca(2+) oscillations; inhibitors
of P/Q and N-type VGCCs were relatively ineffective. Release of Ca(2+) from
intracellular Ca(2+) stores significantly amplified the Ca(2+) signals of
external origin. These results show that a somatic signaling pathway that
generates intracellular Ca(2+) oscillations and involves L-type VGCCs and
intracellular Ca(2+) stores plays a prominent role in the Ca(2+) dynamics of
early developing Purkinje neurons and may play an important role in communicating
developmental cues to the nucleus.
PMID- 11007900
TI - Activity-dependent release of endogenous brain-derived neurotrophic factor from
primary sensory neurons detected by ELISA in situ.
AB - To define activity-dependent release of endogenous brain-derived neurotrophic
factor (BDNF), we developed an in vitro model using primary sensory neurons and a
modified ELISA, termed ELISA in situ. Dissociate cultures of nodose-petrosal
ganglion cells from newborn rats were grown in wells precoated with anti-BDNF
antibody to capture released BDNF, which was subsequently detected using
conventional ELISA. Conventional ELISA alone was unable to detect any increase in
BDNF concentration above control values following chronic depolarization with 40
mM KCl for 72 hr. However, ELISA in situ demonstrated a highly significant
increase in BDNF release, from 65 pg/ml in control to 228 pg/ml in KCl-treated
cultures. The efficacy of the in situ assay appears to be related primarily to
rapid capture of released BDNF that prevents BDNF binding to the cultured cells.
We therefore used this approach to compare BDNF release from cultures exposed for
30 min to either continuous depolarization with elevated KCl or patterned
electrical field stimulation (50 biphasic rectangular pulses of 25 msec, at 20
Hz, every 5 sec). Short-term KCl depolarization was completely ineffective at
evoking any detectable release of BDNF, whereas patterned electrical stimulation
increased extracellular BDNF levels by 20-fold. In addition, the magnitude of
BDNF release was dependent on stimulus pattern, with high-frequency bursts being
most effective. These data indicate that the optimal stimulus profile for BDNF
release resembles that of other neuroactive peptides. Moreover, our findings
demonstrate that BDNF release can encode temporal features of presynaptic
neuronal activity.
PMID- 11007899
TI - Transplanted neuroblasts differentiate appropriately into projection neurons with
correct neurotransmitter and receptor phenotype in neocortex undergoing targeted
projection neuron degeneration.
AB - Reconstruction of complex neocortical and other CNS circuitry may be possible via
transplantation of appropriate neural precursors, guided by cellular and
molecular controls. Although cellular repopulation and complex circuitry repair
may make possible new avenues of treatment for degenerative, developmental, or
acquired CNS diseases, functional integration may depend critically on
specificity of neuronal synaptic integration and appropriate
neurotransmitter/receptor phenotype. The current study investigated
neurotransmitter and receptor phenotypes of newly incorporated neurons after
transplantation in regions of targeted neuronal degeneration of cortical callosal
projection neurons (CPNs). Donor neuroblasts were compared to the population of
normal endogenous CPNs in their expression of appropriate neurotransmitters
(glutamate, aspartate, and GABA) and receptors (kainate-R, AMPA-R, NMDA-R. and
GABA-R), and the time course over which this phenotype developed after
transplantation. Transplanted immature neuroblasts from embryonic day 17 (E17)
primary somatosensory (S1) cortex migrated to cortical layers undergoing
degeneration, differentiated to a mature CPN phenotype, and received synaptic
input from other neurons. In addition, 23.1 +/- 13.6% of the donor-derived
neurons extended appropriate long-distance callosal projections to the
contralateral S1 cortex. The percentage of donor-derived neurons expressing
appropriate neurotransmitters and receptors showed a steady increase with time,
reaching numbers equivalent to adult endogenous CPNs by 4-16 weeks after
transplantation. These results suggest that previously demonstrated changes in
gene expression induced by synchronous apoptotic degeneration of adult CPNs
create a cellular and molecular environment that is both permissive and
instructive for the specific and appropriate maturation of transplanted
neuroblasts. These experiments demonstrate, for the first time, that newly
repopulating neurons can undergo directed differentiation with high fidelity of
their neurotransmitter and receptor phenotype, toward reconstruction of complex
CNS circuitry.
PMID- 11007901
TI - Effect of dexamethasone treatment on maturational changes in the NMDA receptor in
sheep brain.
AB - The objective of the present study was to examine the effect of antenatal or
postnatal treatment with corticosteroids on the NMDA receptor, one of the
mediators of both normal brain development and hypoxic-ischemic injury, by
determining the characteristics of the receptor MK-801 binding site in untreated
and corticosteroid-treated fetal and newborn lambs. (3)H-MK-801 binding was
performed in cerebral cortical cell membranes from fetal sheep at 88, 120, and
136 d gestation (term = 150 d), and from 5-d-old lambs and adult ewes. Animals
were randomized to receive dexamethasone [fetuses: 6 mg, i.m. every 12 hr for
four doses to mother; lambs: 0.01 mg/kg (low dose) or 0.25 mg/kg (high dose)
every 12 hr for four doses] or placebo. During development, B(max) (apparent
number of receptors) increased, reaching a maximum in 5-d-old lambs (p < 0.05)
and decreasing in the adult brain. K(d) (dissociation constant) did not change,
suggesting that receptor affinity was not altered during maturation.
Dexamethasone treatment had no effect on MK-801 binding in the fetus or adult,
but in lambs was associated with a significant decrease in B(max) from 2.17 +/-
0.18 pmol/mg protein in placebo-treated animals to 1.65 +/- 0.8 and 1.62 +/- 0.07
pmol/mg protein in low-dose and high-dose animals, respectively. Affinity for
(3)H-MK-801 decreased 20% after dexamethasone treatment in lambs only (p < 0.05).
Thus, dexamethasone treatment appears to modify the NMDA receptor only during a
specific period of brain development.
PMID- 11007902
TI - Severe hypomyelination of the murine CNS in the absence of myelin-associated
glycoprotein and fyn tyrosine kinase.
AB - The analysis of mice deficient in the myelin-associated glycoprotein (MAG) or
Fyn, a nonreceptor-type tyrosine kinase proposed to act as a signaling molecule
downstream of MAG, has revealed that both molecules are involved in the
initiation of myelination. To obtain more insights into the role of the MAG-Fyn
signaling pathway during initiation of myelination and formation of
morphologically intact myelin sheaths, we have analyzed optic nerves of MAG-, Fyn
and MAG/Fyn-deficient mice. We observed a slight hypomyelination in optic nerves
of MAG mutants that was significantly increased in Fyn mutants and massive in
MAG/Fyn double mutants. The severe morphological phenotype of MAG/Fyn mutants,
accompanied by behavioral deficits, substantiates the importance of both
molecules for the initiation of myelination. The different severity of the
phenotype of different genotypes indicates that the MAG-Fyn signaling pathway is
complex and suggests the presence of compensatory mechanisms in the single
mutants. However, data are also compatible with the possibility that MAG and Fyn
act independently to initiate myelination. Hypomyelination of optic nerves was
not related to a loss of oligodendrocytes, indicating that the phenotype results
from impaired interactions between oligodendrocyte processes and axons and/or
impaired morphological maturation of oligodendrocytes. Finally, we demonstrate
that Fyn, unlike MAG, is not involved in the formation of ultrastructurally
intact myelin sheaths.
PMID- 11007903
TI - Expectation of pain enhances responses to nonpainful somatosensory stimulation in
the anterior cingulate cortex and parietal operculum/posterior insula: an event
related functional magnetic resonance imaging study.
AB - Although behavioral studies suggest that pain distress may alter the perception
of somatic stimulation, neural correlates underlying such alteration remain to be
clarified. The present study was aimed to test the hypothesis that expectation of
pain might amplify brain responses to somatosensory stimulation in the anterior
cingulate cortex (ACC) and the region including parietal operculum and posterior
insula (PO/PI), both of which may play roles in regulating pain-dependent
behavior. We compared brain responses with and subjective evaluation of
physically identical nonpainful warm stimuli between two psychologically
different contexts: one linked with pain expectation by presenting the nonpainful
stimuli randomly intermixed with painful stimuli and the other without. By
applying the event-related functional magnetic resonance imaging technique, brain
responses to the stimuli were assessed with respect to signal changes and
activated volume, setting regions of interest on activated clusters in ACC and
bilateral PO/PI defined by painful stimuli. As a result, the uncertain
expectation of painful stimulus enhanced transient brain responses to nonpainful
stimulus in ACC and PO/PI. The enhanced responses were revealed as a higher
intensity of signal change in ACC and larger volume of activated voxels in PO/PI.
Behavioral measurements demonstrated that expectation of painful stimulus
amplified perceived unpleasantness of innocuous stimulus. From these findings, it
is suggested that ACC and PO/PI are involved in modulation of affective aspect of
sensory perception by the uncertain expectation of painful stimulus.
PMID- 11007904
TI - Definition of neuronal circuitry controlling the activity of phrenic and
abdominal motoneurons in the ferret using recombinant strains of pseudorabies
virus.
AB - During a number of behaviors, including vomiting and some postural adjustments,
activity of both the diaphragm and abdominal muscles increases. Previous
transneuronal tracing studies using injection of pseudorabies virus (PRV) into
either the diaphragm or rectus abdominis (RA) of the ferret demonstrated that
motoneurons innervating these muscles receive inputs from neurons in
circumscribed regions of the spinal cord and brainstem, some of which have an
overlapping distribution in the magnocellular part of the medullary reticular
formation (MRF). This observation raises two possibilities: that two populations
of MRF neurons provide independent inputs to inspiratory and expiratory
motoneurons or that single MRF neurons have collateralized projections to both
groups of motoneurons. The present study sought to distinguish between these
prospects. For this purpose, recombinant isogenic strains of PRV were injected
into these respiratory muscles in nine ferrets; the strain injected into the
diaphragm expressed beta-galactosidase, whereas that injected into RA expressed
green fluorescent protein. Immunofluorescence localization of the unique
reporters of each virus revealed three populations of infected premotor neurons,
two of which expressed only one virus and a third group that contained both
viruses. Dual-infected neurons were predominantly located in the magnocellular
part of the MRF, but were absent from both the dorsal and ventral respiratory
cell groups. These data suggest that coactivation of inspiratory and expiratory
muscles during behaviors such as emesis and some postural adjustments can be
elicited through collateralized projections from a single group of brainstem
neurons located in the MRF.
PMID- 11007905
TI - Parallel streams for the relay of vibrissal information through thalamic
barreloids.
AB - This study investigated the organization of a vibrissal pathway that arises from
the interpolar division of the spinal trigeminal complex (SP5i), transits through
the ventral posterior medial nucleus (VPM), and innervates the somatosensory
cortical areas in the rat. Using Fluoro-Gold and biotinylated dextran amine,
respectively, as retrograde and anterograde tracers, the following organization
plan was disclosed. The SP5i projection arises from a population of small-sized
neurons that selectively innervate the ventral lateral part of VPM. In cytochrome
oxidase-stained material, this region does not display any barreloid arrangement,
but Fluoro-Gold injections in single barrel columns labeled rods of cells that
extend caudally into the ventral lateral division of VPM. Thus, on the basis of
retrograde labeling, barreloids were divided into core and tail compartments,
which correspond to the rod segments running across the dorsal and ventral
lateral parts of VPM, respectively. Double-labeling experiments revealed that
SP5i afferents innervate the tail of barreloids. The anterograde labeling of
thalamocortical axons show that most "core cells" project to a single barrel
column, whereas some "tail cells" give rise to branching axons that innervate the
second somatosensory area and the dysgranular zone of the barrel field.
Injections that straddled the transition zone between the core and tail regions
disclosed cells projecting to a single barrel column and to the surrounding
dysgranular zone. These results suggest that the projection of "barreloids cells"
to the granular and/or dysgranular zones relates to the class of prethalamic
input(s) they receive.
PMID- 11007906
TI - The involvement of recurrent connections in area CA3 in establishing the
properties of place fields: a model.
AB - Strong constraints on the neural mechanisms underlying the formation of place
fields in the rodent hippocampus come from the systematic changes in spatial
activity patterns that are consequent on systematic environmental manipulations.
We describe an attractor network model of area CA3 in which local, recurrent,
excitatory, and inhibitory interactions generate appropriate place cell
representations from location- and direction-specific activity in the entorhinal
cortex. In the model, familiarity with the environment, as reflected by activity
in neuromodulatory systems, influences the efficacy and plasticity of the
recurrent and feedforward inputs to CA3. In unfamiliar, novel, environments,
mossy fiber inputs impose activity patterns on CA3, and the recurrent collaterals
and the perforant path inputs are subject to graded Hebbian plasticity. This
sculpts CA3 attractors and associates them with activity patterns in the
entorhinal cortex. In familiar environments, place fields are controlled by the
way that perforant path inputs select among the attractors. Depending on the
training experience provided, the model generates place fields that are either
directional or nondirectional and whose changes when the environment undergoes
simple geometric transformations are in accordance with experimental data.
Representations of multiple environments can be stored and recalled with little
interference, and these have the appropriate degrees of similarity in visually
similar environments.
PMID- 11007907
TI - Cortical feedback controls the frequency and synchrony of oscillations in the
visual thalamus.
AB - Thalamic circuits have an intrinsic capacity to generate state-dependent
oscillations of different frequency and degrees of synchrony, but little is known
of how synchronized oscillation is controlled in the intact brain or what
function it may serve. The influence of cortical feedback was examined using
slice preparations of the visual thalamus and computational models. Cortical
feedback was mimicked by stimulating corticothalamic axons, triggered by the
activity of relay neurons. This artificially coupled network had the capacity to
self-organize and to generate qualitatively different rhythmical activities
according to the strength of corticothalamic feedback stimuli. Weak feedback (one
to three shocks at 100-150 Hz) phase-locked the spontaneous spindle oscillations
(6-10 Hz) in geniculate and perigeniculate nuclei. However, strong feedback (four
to eight shocks at 100-150 Hz) led to a more synchronized oscillation, slower in
frequency (2-4 Hz) and dependent on GABA(B) receptors. This increase in synchrony
was essentially attributable to a redistribution of the timing of action
potential generation in lateral geniculate nucleus cells, resulting in an
increased output of relay cells toward the cortex. Corticothalamic feedback is
thus capable of inducing highly synchronous slow oscillations in physiologically
intact thalamic circuits. This modulation may have implications for a better
understanding of the descending control of thalamic nuclei by the cortex, and the
genesis of pathological rhythmical activity, such as absence seizures.
PMID- 11007908
TI - Dissociation in conditioned dopamine release in the nucleus accumbens core and
shell in response to cocaine cues and during cocaine-seeking behavior in rats.
AB - The dopaminergic innervation of the nucleus accumbens is generally agreed to
mediate the primary reinforcing and locomotor effects of psychostimulants, but
there is less consensus on conditioned dopamine (DA) release during drug-seeking
behavior. We investigated the neurochemical correlates of drug-seeking behavior
under the control of a drug-associated cue [a light conditioned stimulus (CS+)]
and to noncontingent presentations of the CS+ in the core and shell subregions of
the nucleus accumbens. Rats self-administered cocaine under a continuous
reinforcement schedule in which a response on one of two identical levers led to
an intravenous cocaine infusion (0.25 mg/infusion) and a 20 sec light CS+.
Response requirements for cocaine and the CS+ were then progressively increased
until stable responding was established under a second-order schedule of
reinforcement. During microdialysis, rats were presented noncontingently with a
set of 10 sec CS+ and neutral tone stimuli (CS-) before and after a 90 min period
during which they responded for cocaine under a second-order schedule. Results
showed the following: (1) nucleus accumbens DA increased in both the core and
shell during intravenous cocaine self-administration; (2) noncontingent
presentations of a cocaine-associated CS+ led to increased DA release selectively
in the nucleus accumbens core; and (3) extracellular DA levels were unaltered in
both core and shell during a protracted period of drug-seeking behavior under the
control of the same cocaine-associated cue. These results indicate that the
mesolimbic dopamine system is activated after exposure to drug-associated stimuli
under specific conditions.
PMID- 11007909
TI - Dissociable roles of mid-dorsolateral prefrontal and anterior inferotemporal
cortex in visual working memory.
AB - Functional neuroimaging in human subjects and studies of monkeys with lesions
limited to the mid-dorsolateral (MDL) prefrontal cortex have shown that this
specific region of the prefrontal cortex is involved in visual working memory,
although its precise role remains a matter of debate. The present study compared
the effect on visual working memory of lesions restricted to the mid-dorsolateral
prefrontal cortex of the monkey with that of lesions to the anterior
inferotemporal cortex, a region of the temporal cortex specialized for visual
memory. Increasing the delay during which information had to be maintained in
visual working memory impaired performance after lesions of the anterior
inferotemporal cortex, but not after mid-dorsolateral prefrontal lesions. By
contrast, increasing the number of stimuli that had to be monitored impaired the
performance of animals with mid-dorsolateral prefrontal lesions, but not that of
animals with anterior inferotemporal lesions. This demonstration of a double
dissociation between the effects of these two lesions provides strong evidence
that the role of the mid-dorsolateral prefrontal cortex in visual working memory
does not lie in the maintenance of information per se, but rather in the
executive process of monitoring this information. In addition, the present study
demonstrated that lesions limited to area 9, which constitutes the superior part
of the mid-dorsolateral prefrontal region, give rise to a mild impairment in the
monitoring of information, whereas lesions of the complete mid-dorsolateral
prefrontal region yield a very severe impairment.
PMID- 11007914
TI - Interrupting the inhibiton of normal hematopoiesis in myelogenous leukemia: a
hypothetical approach to therapy.
PMID- 11007915
TI - Suppression of gene expression by targeted disruption of messenger RNA: available
options and current strategies.
AB - At least three different approaches may be used for gene targeting including: A)
gene knockout by homologous recombination; B) employment of synthetic
oligonucleotides capable of hybridizing with DNA or RNA, and C) use of polyamides
and other natural DNA-bonding molecules called lexitropsins. Targeting mRNA is
attractive because mRNA is more accessible than the corresponding gene. Three
basic strategies have emerged for this purpose, the most familiar being to
introduce antisense nucleic acids into a cell in the hopes that they will form
Watson-Crick base pairs with the targeted gene's mRNA. Duplexed mRNA cannot be
translated, and almost certainly initiates processes which lead to its
destruction. The antisense nucleic acid can take the form of RNA expressed from a
vector which has been transfected into the cell, or take the form of a DNA or RNA
oligonucleotide which can be introduced into cells through a variety of means.
DNA and RNA oligonucleotides can be modified for stability as well as engineered
to contain inherent cleaving activity. It has also been proven that because RNA
and DNA are very similar chemical compounds, DNA molecules with enzymatic
activity could also be developed. This assumption proved correct and led to the
development of a "general-purpose" RNA-cleaving DNA enzyme. The attraction of
DNAzymes over ribozymes is that they are very inexpensive to make and that
because they are composed of DNA and not RNA, they are inherently more stable
than ribozymes. Although mRNA targeting is impeccable in theory, many additional
considerations must be taken into account in applying these strategies in living
cells including mRNA site selection, drug delivery and intracellular localization
of the antisense agent. Nevertheless, the ongoing revolution in cell and
molecular biology, combined with advances in the emerging disciplines of genomics
and informatics, has made the concept of nontoxic, cancer-specific therapies more
viable then ever and continues to drive interest in this field.
PMID- 11007916
TI - The role of cytokines and adhesion molecules for mobilization of peripheral blood
stem cells.
AB - CD34(+) hematopoietic stem cells from peripheral blood are commonly used for
autologous or allogeneic transplantation following high-dose therapy in malignant
diseases. The introduction of hematopoietic growth factors such as G-CSF has
greatly facilitated the mobilization of CD34(+) cells. The mechanism of stem cell
mobilization is not yet clear. It seems to be a multistep process with a
crosstalk between cytokines and adhesion molecules. In this review, the role of
hematopoietic growth factors, chemokines, and adhesion molecules for mobilization
and homing of CD34(+) cells is summarized. In addition, factors influencing the
cytokine-induced mobilization in patients and healthy donors are described. The
review closes with an overview of new classes of mobilizing drugs such as
monoclonal antibodies, specific peptides, or antisense oligonucleotides targeting
adhesion molecules.
PMID- 11007917
TI - Thrombopoietin and chemokine mRNA expression in patient post-chemotherapy and in
vitro cytokine-treated marrow stromal cell layers.
AB - CD34(+) cells and megakaryocyte progenitors were lower in marrow from patients
after hematological recovery from the first cycle of 5-fluorouracil, leucovorin,
adriamycin, cyclophosphamide (FLAC) chemotherapy plus PIXY321 (GM-CSF/interleukin
3; IL-3 hybrid) than in FLAC + GM-CSF or pre-FLAC marrows. Marrow stromal layers,
an in vitro model of the marrow microenvironment, express a combination of
stimulatory and inhibitory factors that modulate hematopoietic progenitor cell
proliferation and differentiation. The TaqMan assay and quantitative reverse
transcriptase-polymerase chain reaction were used to measure monocyte
chemoattractant protein-1 (MCP-1), melanoma stimulatory growth activity, and
monokine inducible by interferon-gamma (Mig) (inhibitory chemokines for primitive
or megakaryocyte progenitors) mRNA levels in in vitro PIXY and GM-CSF-treated and
patient post-FLAC marrow stromal layers. Chemokine mRNA was increased after in
vitro GM-CSF and to a lesser extent after PIXY treatment. MCP-1 mRNA levels were
fivefold higher in FLAC + PIXY than in FLAC + GM-CSF layers, and Mig mRNA was
elevated in FLAC + GM-CSF layers. Thrombopoietin (TPO), insulin-like growth
factor I (IGF-I), and IGF-II (stimulatory factors for primitive and megakaryocyte
progenitors) mRNA were also measured. TPO mRNA levels were 30% lower in GM-CSF
and PIXY-pretreated than in control layers with no decrease in IGF mRNA. TPO mRNA
in stromal layers of patients who developed grade 3 thrombocytopenia (platelets <
20 x 10(9)/l) during the third cycle of FLAC was only 24% of levels in stromal
layers of marrow from other post-FLAC patients. Results demonstrate that patient
and in vitro treatment had modulatory effects on TPO and chemokine mRNA
expression in marrow stromal layers.
PMID- 11007918
TI - New strategies in the treatment of acute myelogenous leukemia: mobilization and
transplantation of autologous peripheral blood stem cells in adult patients.
AB - During the last decade high-dose Ara-C (HIDAC; single doses of 3 g/m(2)) and
autologous stem cell transplantation have been increasingly used as postremission
therapy in adult acute myelogenous leukemia (AML). Controlled clinical trials
have demonstrated a long-term disease-free survival of 40%-50% for patients
treated with at least two courses of HIDAC. Other studies have demonstrated that
postremission autologous bone marrow transplantation results in a disease-free
survival equal to or better than conventional chemotherapy. However,
autotransplantation with mobilized peripheral blood stem cells (PBSC) would now
be preferred instead of autologous bone marrow, due to the shorter hematopoietic
reconstitution period. The results reviewed in the present article suggest that
HIDAC and autologous PBSC transplantation can be combined in the postremission
treatment of adult AML, and this combination therapy may also reduce minimal
residual disease and the risk of posttransplant relapse. From the available
studies it cannot be concluded whether graft purging further reduces the relapse
risk. However, the possible advantage of combination therapy with repeated
courses of HIDAC and autologous PBSC transplantation needs to be demonstrated in
prospective clinical trials before it can be recommended as a part of the routine
treatment in AML.
PMID- 11007919
TI - Lentiviral vector transduction of hematopoietic stem cells that mediate long-term
reconstitution of lethally irradiated mice.
AB - Lentiviral vectors efficiently transduce human CD34(+) cells that mediate long
term engraftment of nonobese diabetic/severe combined immunodeficient mice.
However, hematopoiesis in these animals is abnormal. Typically, 95% of the human
cells in peripheral blood are B lymphocytes. To determine whether lentiviral
vectors efficiently transduce stem cells that maintain normal hematopoiesis in
vivo, we isolated Sca-1(+)c-Kit(+)Lin(-) bone marrow cells from mice without 5
fluorouracil treatment, and transduced these cells in the absence of cytokine
stimulation with a novel lentiviral vector containing a GFP (green flourescent
protein) reporter gene. These cells were transplanted into lethally irradiated
C57Bl/6 mice. In fully reconstituted animals, GFP expression was observed in 8.0%
of peripheral blood mononuclear cells for 20 weeks posttransplantation. Lineage
analysis demonstrated that a similar percentage (approximately 8.0%) of GFP
positive cells was detected in peripheral blood B cells, T cells, granulocytes
and monocytes, bone marrow erythroid precursor cells, splenic B cells, and thymic
T cells. In secondary transplant recipients, up to 20% of some lineages expressed
GFP. Our results suggest that quiescent, hematopoietic stem cells are efficiently
transduced by lentiviral vectors without impairing self-renewal and normal
lineage specification in vivo. Efficient gene delivery into murine stem cells
with lentiviral vectors will allow direct tests of genetic therapies in mouse
models of hematopoietic diseases such as sickle cell anemia and thalassemia, in
which corrected cells may have a selective survival advantage.
PMID- 11007920
TI - The pharmacokinetics and pharmacodynamics of GW395058, a peptide agonist of the
thrombopoietin receptor, in the dog, a large-animal model of chemotherapy-induced
thrombocytopenia.
AB - GW395058, a PEGylated peptide agonist of the thrombopoietin receptor, stimulates
megakaryocytopoiesis and has previously been shown to increase platelet counts in
vivo. The pharmacokinetics and pharmacodynamics of GW395058 were characterized
using a randomized, crossover study in a large-animal model (dog) of chemotherapy
induced thrombocytopenia. Nine beagle dogs received i.v. carboplatin (350
mg/m(2)) on day 0 and day 28. GW395058 (1.31 mg/kg) (n = 6) or vehicle control (n
= 3) was administered on day 1 and day 29 either as an i.v. bolus or s.c.
injection. After i.v. administration, peak concentrations of GW395058 occurred
rapidly, while the half-life averaged approximately 56 h. Bioavailability (+/-
standard deviation) of GW395058 given s.c. was 78.2% (20.9%). GW395058 (i.v. and
s.c.) ameliorated the platelet nadir (p = 0.0086) and resulted in a shorter time
to recovery compared to the control group. The mean nadir platelet counts
following carboplatin administration were 197,000 cells/microl (80,000) for the
i.v. GW395058-dose group, 183,000 cells/microl (72,000) for the s.c.-dose group
and 71,000 cells/microl (38,000) for the vehicle-alone group. GW395058 reduced
the thrombocytopenic effects of carboplatin in dogs. No GW395058-related adverse
side effects were observed.
PMID- 11007921
TI - Signaling induced by erythropoietin and stem cell factor in UT-7/Epo cells:
transient versus sustained proliferation.
AB - UT-7/Epo cells are human factor-dependent erythroleukemic cells, requiring
erythropoietin (Epo) for long-term growth. Stem cell factor (SCF) stimulates
proliferation of UT-7/Epo only transiently, for three to five days. An
investigation of the signal transduction pathways activated by these cytokines in
UT-7/Epo cells may identify those signals specifically required for sustained
growth. Proliferation assays demonstrate that SCF generates a substantial growth
response in UT-7/Epo cells; however, the cells do not multiply or survive past
five to seven days. While Epo induces the activation of JAK2 and STAT5, SCF
stimulation shows no activation of JAK2 or STATs 1, 3, or 5. The activation of
MAPK (p42/44) by SCF was transient, lasting only 30 min, in contrast to Epo,
which stimulated phosphorylation of p42/44 for up to 2 h. The expression of the
early response genes c-fos, egr1, and cytokine-inducible SH2 protein (CIS) in
response to SCF or Epo stimulation demonstrated that the transient expression of
p42/44 correlated with the transient expression of c-fos and egr1. In addition,
CIS was activated by Epo but not SCF. These data indicate that EpoR, JAK2, and
STAT5 activation are not required for the initiation of proliferation of these
erythroid cells, that the transient activation of p42/44 correlates with the
transient gene expression of c-fos and egr1, and sustained expression of c-fos
and egr1 as seen in UT-7/Epo cells continuously grown in Epo may be necessary for
long-term proliferation.
PMID- 11007922
TI - Characterization of chemokine receptors expressed in primitive blood cells during
human hematopoietic ontogeny.
AB - Chemokines are capable of regulating a variety of fundamental processes of
hematopoietic cells that include proliferation, differentiation, and migration.
To evaluate potential chemokine signaling pathways important to the regulation of
primitive human hematopoietic cells, we examined chemokine receptor expression of
highly purified subpopulations of uncommitted human blood cells. CXCR1-, CXCR2-,
CXCR4-, and CCR5-expressing cells were detected by flow cytometry among human
blood subsets depleted of lineage-restricted cells (Lin(-)) derived from adult
bone marrow, mobilized peripheral blood, cord blood (CB), and circulating fetal
blood. Although these chemokine receptors could be detected on Lin(-) cells
throughout human development, only CXCR4 could be detected in CD34(-)CD38(-)Lin(
) and CD34(+)CD38(-)Lin(-) subfractions enriched for stem cell function,
suggesting that independent of ontogeny, CXCR4-mediated signals are critical to
primitive hematopoiesis. Distinct to other stages of human hematopoietic
development, primitive CB cells expressed higher levels of CXCR1, CXCR2, CCR5,
and CXCR4 on both CD34(-)CD38(-)Lin(-) and CD34(+)CD38(-)Lin(-) subsets.
Isolation of these fractions revealed expression of additional chemokine
receptors CCR7, CCR8, and Bonzo (STRL133), whereas BOB (GPR15) could not be
detected. Our study illustrates that rare uncommitted hematopoietic cells express
chemokine receptors not previously associated with primitive human blood cells.
Based on these results, we suggest that signaling pathways mediated by chemokine
receptors identified here may play a fundamental role in hematopoietic stem cell
regulation and provide alternative receptor targets for retroviral pseudotyping
for genetic modification of repopulating cells.
PMID- 11007923
TI - The molecular perspective: microtubules and the taxanes.
PMID- 11007924
TI - Immunotoxin-induced apoptosis.
PMID- 11007925
TI - Potential role for NGF in breast cancer.
PMID- 11007926
TI - SODD-silencer of death domains.
PMID- 11007927
TI - A challenge to solve "Lichtman's riddles".
PMID- 11007928
TI - Melanocyte development and malignant melanoma.
AB - Malignant melanoma is a notoriously aggressive disease that can affect relatively
young individuals and whose incidence is rising at an alarming rate. Unlike many
cancers, metastatic melanoma is poorly responsive to current therapies and
mutations affecting p53, the retinoblastoma gene product or Ras which occur
frequently in many other cancer types, appear to be rare or at least relatively
late events in the progression of the disease. Recent advances in our
understanding of the disease at the molecular level have indicated that in
addition to the loss of cell cycle checkpoints which may be common to all
cancers, malignant melanoma shares many characteristics in common with
developmental precursors to melanocytes, the mature pigment producing cells of
the skin and hair follicles which are responsible for skin and hair colour. This
review therefore focuses on the signalling pathways that play a crucial role in
the development of the melanocyte lineage which are subject to deregulation in
malignant melanoma namely signalling by receptor tyrosine kinases, the Wnt
signalling pathway, as well as loss of the p16INK4a cyclin-dependent kinase
inhibitor. Intriguingly all three pathways impact on the expression or function
of the microphthalmia-associated transcription factor which plays an essential
role in melanocyte development.
PMID- 11007929
TI - Gene-environment interaction in melanoma.
AB - Gene-environment interaction can be defined as a different effect of an
environmental exposure in people with different genotypes, or a different effect
of a genotype in people with different histories of environmental exposure.
Interaction applies when one stratum (high risk) responds differently to an
exposure (sun) than another stratum (low risk). Genetic predisposition would
appear to be a very important modifier of risk. This paper discusses the concept
of gene-environment interaction applied to cutaneous melanoma through discussion
of highly penetrant genes and their interaction with sun exposure, through
discussion of low penetrant genes and their interaction with sun exposure, and by
suggesting a new model for investigation of gene-environment interaction in
melanoma. It is stressed that this area of investigation is extremely early in
its development.
PMID- 11007930
TI - Cytokine-based therapy for melanoma: pre-clinical studies.
AB - Incidence and mortality of human malignant melanoma has risen rapidly over recent
decades. Systemic therapies for metastatic cutaneous melanoma, the most
aggressive of all skin cancers, remain disappointing although immunological
treatment has been more successful for melanoma than for most other tumours. With
the availability of recombinant cytokines, immunotherapy for melanoma has entered
a new era and a growing body of evidence suggests the efficacy of these
approaches in pre-clinical models. Cytokine gene transfer to tumour cells has
been demonstrated to induce tumour rejection in different murine melanoma models
suggesting that vaccination with tumour cells genetically engineered to produce
cytokines is an attractive strategy to enhance anti-tumour immune responses in
patients with melanoma. Taken together, these data may hold significant promise
for the development of effective ex vivo and in vivo systemic and gene therapy
modalities to counter the highly metastatic nature of human melanoma.
PMID- 11007931
TI - Update on the role of adjuvant interferon for high risk melanoma.
AB - Major prognostic factors for melanoma include thickness of the primary lesion,
ulceration and presence or absence of regional lymph node metastases. These
parameters form the basis for the American Joint Committee on Cancer staging
system and the determination of the appropriateness of post-surgical adjuvant
therapy. Among the numerous agents tested for the adjuvant therapy of high-risk
melanoma, interferon-alpha 2b (IFN-alpha2b) administered at maximally tolerated
doses is the only one to demonstrate an improvement in relapse-free and overall
survival for these patients. This high-dose IFN-alpha2b regimen comprising an
intensive intravenous induction phase followed by a more prolonged subcutaneously
administered phase has now been tested in three, large, randomised trials done
through the United States Cooperative Groups, and has shown consistent benefit in
preventing relapse and improving survival for patients with thick primary
melanomas and those with regional lymph node metastases. The relative importance
of the induction component of this treatment regimen is being addressed in an
ongoing intergroup trial for intermediate-risk melanoma. Data from completed and
ongoing studies using high-dose IFN-alpha for the adjuvant therapy of melanoma
are presented.
PMID- 11007932
TI - Immunologically-mediated tumour cell apoptosis: the role of TRAIL in T cell and
cytokine-mediated responses to melanoma.
AB - Immune responses against human melanoma are common and are believed to influence
the natural history of the disease. In particular, CD4 T cell infiltrates are
associated with regression of primary melanoma and with responses to treatment
with interferon-alpha2 (IFN-alpha2). Our studies have shown that CD4 T cells
appear to kill melanoma by means of a member of the tumour necrosis factor (TNF)
family expressed on their surface and called TNF related apoptosis inducing
ligand (TRAIL). Moreover, sensitivity to TRAIL also predicts responsiveness of
melanoma to CD4 T cells. TRAIL is not expressed on resting lymphocytes but is
expressed at high levels after exposure to IFN-alpha2 and on activated T cells.
Lymphocytes from melanoma patients in early stages of the disease show high
levels of expression after exposure to IFN-alpha2 and IFN-gamma but expression
was less on lymphocytes from stage IV patients. This may be due to factors from
melanoma cells in that supernatants from some melanoma cultures suppressed IFN
alpha2 upregulation of TRAIL. Sensitivity of melanoma cells to TRAIL can be
increased by inhibition of the activation of NF-kappaB and anti-apoptotic events
downstream of NF-kappaB. These results suggest that TRAIL may be an important
mediator of responses against melanoma induced by immunotherapy or by treatment
with IFN-alpha2 and interleukin-2. Studies on surgical biopsies of melanoma
however show that fresh isolates appear less sensitive to TRAIL-induced apoptosis
and effective therapy may involve combinations with other agents.
PMID- 11007933
TI - Melanoma antigens recognised by CD8+ and CD4+ T cells.
AB - The field of melanoma immunobiology has made tremendous strides in the past
decade, resulting in the molecular identification of a vast array of tumour
expressed antigens that contain determinants that are recognised by patient T
cells or immunoglobulins. The integration of these antigens, their derivative
peptides or improved analogues in vaccine trials allows for the augmentation of
melanoma-specific CD4+ and CD8+ T cells in situ that may prove clinically
efficacious in the adjuvant or therapeutic setting. Indeed, melanoma peptide
based immunotherapies targeting the activation of anti-tumour CD8+ cytotoxic T
lymphocytes have proven successful (i.e. yielding objective clinical responses),
particularly when combined with T cell growth factors or potent antigen
presenting cells, such as dendritic cells. Vaccine approaches implementing poly
epitope and/or melanoma peptides recognised by CD4+ T cells are anticipated to
yield still better clinical outcomes due to the in vivo promotion and maintenance
of a diversified, poly-specific effector T cell repertoire directed against
resident tumours.
PMID- 11007934
TI - New cytotoxic agents for the treatment of metastatic malignant melanoma:
temozolomide and related alkylating agents in combination with guanine analogues
to abrogate drug resistance.
AB - The chloroethylating nitrosoureas (lomustine, fotemustine, cystemustine (BCNU)
and methylating agents temozolomide (TMZ), dacarbazine (DTIC), procarbazine) have
documented activity in metastatic malignant melanoma with single agent response
rates of 15-25%. Chloroethylating agents form chloroethyl adducts at the O6
position of guanine, resulting in N1-guanine, N3-cytosine interstrand crosslinks
which are cytotoxic. Methylating agents attack DNA at multiple sites, although
most of their cytotoxic activity is due to the formation of methyl adducts at the
O6 position of guanine. The presence of these adducts results in a futile
recycling of the mismatch repair pathway resulting in DNA strand breaks and
apoptotic cell death. An intact mismatch repair system is required to achieve
their cytotoxic effect. Repair of adducts by the DNA repair protein O6
alkylguanine DNA alkyltransferase (AGT) impairs the cytotoxic action of both
methylating and chloroethylating agents, and mediates a major resistance pathway
to these drugs. During DNA repair, irreversible inactivation of AGT occurs. To
regenerate AGT activity, synthesis of new molecules is required. Increased but
variable AGT activity is found in malignant melanoma, is higher in metastatic
lesions than in primary tumours, and is higher in tumours than normal skin.
Expression of AGT activity, is higher in melanoma metastases after DTIC
chemotherapy compared to expression prior to therapy. TMZ alone depletes human
AGT in tumour tissue and peripheral blood progenitor cells. As the t1/2 of TMZ
via the oral route is short (approximately 1.8 hours), and the anti-tumour
activity of the drug is known to be schedule-dependent, twice daily or prolonged
administration schedules of TMZ prevent regeneration of AGT, and render tumour
cells more sensitive to the drug. O6-benzylguanine (BG) is a potent AGT
inactivating agent. BG and its analogues reduce AGT activity, and increase the in
vitro and in vivo efficacy of both methylating and chloroethylating agents. In
clinical trials, non-toxic doses of BG deplete AGT to undetectable levels. AGT
depleting agents in combination with methylating and chloroethylating agents are
now in clinical testing, and may result in greater clinical efficacy in
metastatic malignant melanoma.
PMID- 11007935
TI - Protein recruitment systems for the analysis of protein-protein interactions.
AB - Following the completion of genome projects in a number of organisms, it is
becoming evident that a relatively large proportion of the genes identified
encode for proteins that have no sequence homology with known proteins. One
possible approach towards understanding protein function is to identify the
proteins with which a particular protein associates. Although very powerful, the
most commonly used genetic method, the two-hybrid system, is limited in its
ability to detect all possible protein-protein interactions. The development of
novel approaches, such as the protein recruitment systems, provides attractive
alternatives towards identification of protein-protein interactions where other
methods have failed to function.
PMID- 11007936
TI - c-Jun and the transcriptional control of neuronal apoptosis.
AB - There has been considerable interest in the molecular mechanisms of apoptosis in
mammalian neurons because this form of neuronal cell death is important for the
normal development of the nervous system and because inappropriate neuronal
apoptosis may contribute to the pathology of human neurodegenerative diseases.
The aim of recent research has been to identify the key components of the cell
death machinery in neurons and understand how the cell death programme is
regulated by intracellular signalling pathways activated by the binding of
neurotrophins or death factors to specific cell surface receptors. The aim of
this commentary was to review research that has investigated the role of the Jun
N-terminal kinase (JNK)/c-Jun signalling pathway in neuronal apoptosis, focusing
in particular on work carried out with developing sympathetic neurons.
Experiments with sympathetic neurons cultured in vitro, as well as with
cerebellar granule neurons and differentiated PC12 cells, have demonstrated that
JNK/c-Jun signalling can promote apoptosis following survival factor withdrawal.
In addition, experiments with Jnk(-/-) knockout mice have provided evidence that
Jnk3 may be required for apoptosis in the hippocampus in vivo following injection
of kainic acid, an excitotoxin, and that Jnk1 and Jnk2 are required for apoptosis
in the developing embryonic neural tube. However, in the embryonic forebrain,
Jnk1 and Jnk2 have the opposite function and are necessary for the survival of
developing cortical neurons. These results suggest that JNKs and c-Jun are
important regulators of the cell death programme in the mammalian nervous system,
but that their biological effects depend on the neuronal type and stage of
development.
PMID- 11007937
TI - Therapeutic RNA and DNA enzymes.
AB - Recent progress in understanding how gene products interact in the control of
cell proliferation has engendered high hopes for the rational design of specific
therapeutic strategies. The demonstration that certain RNA and DNA nucleic acids
can enzymatically cleave mRNAs has offered the possibility of inactivating
abnormal gene expression. In principle, this technology is applicable to any
disease where a specific gene product can be linked to the initiation and/or
perpetuation of the disease. Here, a brief description of the technology that can
be useful for the design of therapeutic DNA and RNA agents capable of inducing
apoptosis in cancer cells is presented. Furthermore, such agents can be a
valuable tool for probing gene function.
PMID- 11007939
TI - Apoptosis and nuclear factor-kappa B: a tale of association and dissociation.
AB - It is not clear why on treatment with certain killer cytokines or
chemotherapeutic agents, some cells undergo apoptosis while others do not. The
delineation of sensitivity/resistance pathways should provide a more specific
therapy for cancer and other hyperproliferative diseases. Most cells die either
by apoptosis or by necrosis. The biochemical pathway that mediates these two
modes of cell death has recently been described. The nuclear factor (NF)-kappa B
and the genes regulated by this transcription factor have been shown to play a
critical role in induction of resistance to killer agents. Thus, inhibitors of NF
kappa B activation have a potential in overcoming resistance to apoptosis induced
by various agents. The evidence for and against such a notion is discussed.
PMID- 11007938
TI - Regulation of the peroxisomal beta-oxidation-dependent pathway by peroxisome
proliferator-activated receptor alpha and kinases.
AB - The first PPAR (peroxisome proliferator-activated receptor) was cloned in 1990 by
Issemann and Green (Nature 347:645-650). This nuclear receptor was so named since
it is activated by peroxisome proliferators including several drugs of the
fibrate family, plasticizers, and herbicides. This receptor belongs to the
steroid receptor superfamily. After activation by a specific ligand, it binds to
a DNA response element, PPRE (peroxisome proliferator response element), which is
a DR-1 direct repeat of the consensus sequence TGACCT x TGACCT. This mechanism
leads to the transcriptional activation of target genes (Motojima et al., J Biol
Chem 273:16710-16714, 1998). After the first discovery, several isoforms were
characterized in most of the vertebrates investigated. PPAR alpha, activated by
hypolipidemic agents of the fibrate family or by leukotrienes; regulates lipid
metabolism as well as the detoxifying enzyme-encoding genes. PPAR beta/delta,
which is not very well known yet, appears to be more specifically activated by
fatty acids. PPAR gamma (subisoforms 1, 2, 3) is activated by the prostaglandin
PGJ2 or by antidiabetic thiazolidinediones (Vamecq and Latruffe, Lancet 354:411
418, 1999). This latter isoform is involved in adipogenesis. The level of PPAR
expression is largely dependent on the tissue type. PPAR alpha is mainly
expressed in liver and kidney, while PPAR beta/delta is almost constitutively
expressed. In contrast, PPAR gamma is largely expressed in white adipose tissue.
PPAR is a transcriptional factor that requires other nuclear proteins in order to
function, i.e. RXRalpha (9-cis-retinoic acid receptor alpha) in all cases in
addition to other regulatory proteins. Peroxisomes are specific organelles for
very long-chain and polyunsaturated fatty acid catabolism. From our results and
those of others, the inventory of the role of PPAR alpha in the regulation of
peroxisomal fatty acid beta-oxidation is presented. In relation to this, we
showed that PPAR alpha activates peroxisomal beta-oxidation-encoding genes such
as acyl-CoA oxidase, multifunctional protein, and thiolase (Bardot et al., FEBS
Lett 360:183-186, 1995). Moreover, rat liver PPAR alpha regulatory activity is
dependent on its phosphorylated state (Passilly et al., Biochem Pharmacol 58:1001
1008, 1999). On the other hand, some signal transduction pathways such as protein
kinase C are modified by peroxisome proliferators that increase the
phosphorylation level of some specific proteins (Passilly et al. Eur J Biochem
230:316-321, 1995). From all these findings, PPAR alpha and kinases appear to
play an important role in lipid homeostasis.
PMID- 11007940
TI - Regulation of nuclear factor-kappa B, activator protein-1, and glutathione levels
by tumor necrosis factor-alpha and dexamethasone in alveolar epithelial cells.
AB - The development of an oxidant/antioxidant imbalance in lung inflammation may
activate redox-sensitive transcription factors such as nuclear factor-kappa B (NF
kappa B) and activator protein-1 (AP-1), which regulate the genes for
proinflammatory mediators and protective antioxidant genes. GSH, a ubiquitous
tripeptide thiol, is a vital intra- and extracellular protective antioxidant
against oxidative stress, which plays a key role in the control of
proinflammatory processes in the lungs. The rate-limiting enzyme in GSH synthesis
is gamma-glutamylcysteine synthetase (gamma-GCS), which consists of a catalytic
heavy and a regulatory light subunit. The promoter regions of the human gamma-GCS
subunits contain AP-1, NF-kappa B, and antioxidant response elements and are
regulated by oxidants, growth factors, inflammatory cytokine tumor necrosis
factor-alpha (TNF-alpha), and anti-inflammatory agent (dexamethasone) in lung
cells. TNF-alpha depletes intracellular GSH, concomitant with an increase in
oxidised glutathione levels in alveolar epithelial cells. TNF-alpha also induces
the activation of NF-kappa B and AP-1 and the subsequent increase in gamma-GCS
heavy subunit transcription in these cells. Dexamethasone depleted both basal and
TNF-alpha-stimulated GSH levels by down-regulating the gamma-GCS-heavy subunit
transcription via a mechanism involving AP-1 (c-Jun). The existence of this fine
tuning between the redox GSH levels and the activation of transcription factors
may determine the balance of transcription for proinflammatory and antioxidant
gamma-GCS genes in inflammation. More studies are required to understand the
signalling mechanism of the redox regulation of NF-kappa B and AP-1 and gene
transcription in inflammation. This could lead to the development of therapeutic
strategies based on the pharmacological manipulation of the production of this
important antioxidant in inflammation.
PMID- 11007941
TI - Cell signaling and regulators of cell cycle as molecular targets for prostate
cancer prevention by dietary agents.
AB - Prostate cancer (PCA) is the most common invasive malignancy and leading cause
(after lung) of cancer deaths in males. Since PCA is initially androgen
dependent, strategies are targeted toward androgen depletion for its control.
However, tumor re-growth mostly occurs following this modality, and is androgen
independent. A loss of functional androgen receptor and an enhanced expression of
growth factor receptors (e.g. erbB family members) and associated ligands have
been shown to be the causal genetic events in PCA progression. These genetic
alterations lead to an epigenetic mechanism where a feed-back autocrine loop
between membrane receptor (e.g. epidermal growth factor receptor [erbB1] and
associated ligand (e.g. transforming growth factor-alpha) results in an enhanced
activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) as an
essential component of the uncontrolled growth of PCA at an advanced and androgen
independent stage. Together, we rationalized that inhibiting these epigenetic
events would be useful in controlling advanced PCA growth. Dietary polyphenolic
flavonoids and isoflavones are being studied extensively as cancer-preventive and
interventive agents. Therefore, we focused our attention on silymarin, genistein,
and epigallocatechin 3-gallate (EGCG), present in milk thistle, soy beans, and
green tea, respectively. The effect of these agents was assessed on the erbB1-Shc
ERK1/2 signal transduction pathway, cell cycle regulatory molecules, and cell
growth and death. In androgen-independent human prostate carcinoma DU145 cells,
silymarin, genistein, and EGCG resulted in a significant to complete inhibition
of transforming growth factor-alpha-caused activation of membrane receptor erbB1
followed by inhibition of downstream cytoplasmic signaling target Shc activation
and a decrease in its binding with erbB1, without an alteration in their protein
expression. Silymarin and genistein also inhibited ERK1/2 activation, suggesting
that these agents impair the activation of erbB1-Shc-ERK1/2 signaling in DU145
cells. In the case of EGCG, a further increase in ERK1/2 activation was observed
that was related to its pro-oxidant and apoptotic activities. Silymarin,
genistein, and EGCG also resulted in a significant induction of Cip1/p21 and
Kip1/p27 and a decrease in cyclin-dependent kinase (CDK) 4, but a moderate
inhibition of CDK2, cyclin D1, and cyclin E was observed. An enhanced level of
Cip1/p21 and Kip1/27 also led to an increase in their binding to CDK4 and CDK2.
Treatment of cells with silymarin, genistein, and EGCG also resulted in strong
cell growth inhibition at lower doses, and complete inhibition at higher doses.
In contrast to silymarin, higher doses of genistein also showed cell death. A
more profound cytotoxic effect was observed in the case of EGCG, with strong cell
death at lower doses and complete loss of viability at higher doses. Together,
these results suggest that cell signaling and regulators of cell cycle are
potential epigenetic molecular targets for prostate cancer prevention by dietary
agents. More studies, therefore, are needed with these agents to explore their
anticarcinogenic potential against human prostate cancer.
PMID- 11007942
TI - Inhibitors of prenylation of Ras and other G-proteins and their application as
therapeutics.
AB - Anchoring of small G-proteins to cellular membranes via a covalently bound
lipophylic prenyl group is essential for the functioning of these proteins. For
example, the farnesylation of Ras by the action of the enzyme protein:farnesyl
transferase (PFT) is pivotal for its signalling function in cell growth and
differentiation. The development of inhibitors of PFT was triggered by the role
of mutated Ras in certain types of cancer and by the observation that non
farnesylated Ras is inactive. Besides the screening of existing compounds for PFT
inhibition, rational drug design has also led to new inhibitors. Our research is
in the field of atherosclerosis and concerns the development of inhibitors of the
growth of vascular smooth muscle cells. The latter process gives rise to
reocclusion of the coronary artery (restenosis) after balloon angioplasty. We and
others have developed several analogues of the two substrates of PFT, i.e.
farnesyl pyrophosphate (FPP) and the so-called CAAX peptide consensus sequence,
which were tested in vitro for the inhibition of PFT and of other enzymes
involved in protein prenylation, such as protein:geranylgeranyl transferase-1
(PGGT-1). The FPP analogue TR006, a strong inhibitor of PFT (IC(50) of 67 nM),
blocked the proliferation of cultured human smooth muscle cells and inhibited
platelet-derived growth factor- and basic fibroblast growth factor-induced DNA
synthesis. Similar but more highly charged compounds failed in this respect,
probably because of an impaired uptake in the cells. Less charged derivatives
were designed to circumvent this problem. The effect on the GF-induced activation
of intermediates in signal transduction pathways was investigated in order to
gain insight into the mechanism of action within the cells. TR006 decreased the
bFGF activation of extracellular signal-regulated kinase 1 (ERK1), suggesting its
involvement in inhibiting Ras activity. Although other analogues inhibited DNA
synthesis, they affected neither ERK1 activation nor p38/stress-activated protein
kinase 2 or Jun N-terminal kinase 1 activation. Since some of these compounds
were also shown to be inhibitors of in vitro PGGT-1 activity, the
geranylgeranylation of other G-proteins may be decreased by these compounds. Rho
seems to be a good candidate as a target for inhibitors of PGGT-1. This
uncertainty as to the mechanism of action within non-transformed as well as
transformed cells applies to all prenylation inhibitors, but is not holding back
their further development as drugs. Their current and possible future application
as therapeutics in cancer, restenosis, angiogenesis, and osteoporosis is briefly
discussed.
PMID- 11007943
TI - The integrin alpha IIb/beta 3 in human platelet signal transduction.
AB - Platelets are critical for the maintenance of the integrity of the vascular
system and are the first line of defence against haemorrhage. When they encounter
a subendothelial matrix exposed by injury to a vessel, platelets adhere, are
activated, and become adhesive for other platelets so that they aggregate. alpha
IIb/beta 3, a platelet-specific integrin, is largely prominent amongst the
adhesion receptors and is essential for platelet aggregation. The ligands for
alpha IIb/beta 3 are the multivalent adhesive proteins fibrinogen and von
Willebrand factor. In resting platelets, alpha IIb/beta 3 is normally in a low
activation state, unable to interact with soluble fibrinogen. Stimulation of
platelets with various agonists will induce a conformational change in alpha
IIb/beta 3 (inside-out signalling), which is then able to bind soluble fibrinogen
resulting in the onset of platelet aggregation. However, fibrinogen binding to
its membrane receptor is not simply a passive event allowing the formation of
intercellular bridges between platelets. Indeed, a complex signalling pathway
triggered by integrin ligation and clustering (outside-in signalling) will
regulate the extent of irreversible platelet aggregation and clot retraction.
Amongst the signalling enzymes activated downstream of alpha IIb/beta 3
engagement, phosphoinositide 3-kinase plays an important role in the control of
the irreversible phase of aggregation.
PMID- 11007944
TI - Oxidative stress interference with the nuclear factor-kappa B activation
pathways.
AB - While intracellular redox balance is tightly controlled in many cell types, its
modification leads to important cellular changes derived, in part, from a
modification of the pattern of gene expression. This modification relies on many
transcription factors whose activities are either increased or reduced by a
disbalance of the redox environment. Among these transcription factors, nuclear
factor-kappa B (NF-kappa B) plays a pivotal role in inducing genes involved in
the control of the immune system as well as in the response to injury and
infection. Because NF-kappa B can be induced in many cells by a diverse set of
stimulating agents, it has been proposed that agents activating it do so by
increasing oxidative stress within the cell. However, this model was not found to
be universal, since the dependence between NF-kappa B activation and
intracellular reactive oxygen species (ROS) generation was only detected in
certain cell lines. The origin of this dependency is still unknown, but could
very well be situated in a particular kinase or in adaptator molecules of the
signaling cascade, leading to inhibitor kappa B alpha (I kappa B alpha
phosphorylation. On the other hand, NF-kappa B can be activated by oxidants in
many cell types, but this activation is well characterized only in lymphocytes.
This activation is distinct from that of classical activators such as
proinflammatory cytokines and phorbol esters, because the activation mechanisms
appear to converge on a particular tyrosine residue of I kappa B-alpha instead of
the two classical N-terminal serines. The nature of the protein kinases or
protein phosphatases involved in this process is still undetermined. It will be a
challenge in the future to identify the kinases/phosphatases activated by
oxidants and to discover why ROS are required in some cells to turn on the
transduction pathway leading to NF-kappa B activation by physiological stimuli.
PMID- 11007945
TI - Nuclear factor-kappa B, cancer, and apoptosis.
AB - The role of nuclear factor (NF)-kappa B in the regulation of apoptosis in normal
and cancer cells has been extensively studied in recent years. Constitutive NF
kappa B activity in B lymphocytes as well as in Hodgkin's disease and breast
cancer cells protects these cells against apoptosis. It has also been reported
that NF-kappa B activation by tumor necrosis factor (TNF)-alpha, chemotherapeutic
drugs, or ionizing radiations can protect several cell types against apoptosis,
suggesting that NF-kappa B could participate in resistance to cancer treatment.
These observations were explained by the regulation of antiapoptotic gene
expression by NF-kappa B. However, in our experience, inhibition of NF-kappa B
activity in several cancer cell lines has a very variable effect on cell
mortality, depending on the cell type, the stimulus, and the level of NF-kappa B
inhibition. Moreover, in some experimental systems, NF-kappa B activation is
required for the onset of apoptosis. Therefore, it is likely that the NF-kappa B
antiapoptotic role in response to chemotherapy is cell type- and signal-dependent
and that the level of NF-kappa B inhibition is important. These issues will have
to be carefully investigated before considering NF-kappa B as a target for
genetic or pharmacological anticancer therapies.
PMID- 11007946
TI - Induction and regulation of epithelial-mesenchymal transitions.
AB - Herein we discuss the factors that bring about the transformation of epithelial
cells into cells of fibroblastic phenotype. This type of transformation, referred
to as epithelium-to-mesenchyme transition (EMT), allows cells to dissociate from
the epithelial tissue from which they originate and to migrate freely. EMT is
therefore thought to play a fundamental role during the early steps of invasion
and metastasis of carcinoma cells. Among biological agents which have been
identified as inducers of EMT are a number of cytokines and extracellular matrix
macromolecules. The coordinated changes in cell morphology, associated with the
induction of cell motility and the disruption of intercellular junctions, are the
consequence of a signaling cascade emanating from the plasma membrane and leading
to changes in gene expression. Understanding the mechanisms regulating EMT of
normal and transformed epithelial cells may offer new perspectives for designing
therapies for the treatment of metastatic cancers of epithelial origin.
PMID- 11007947
TI - Inhibition of the type I insulin-like growth factor receptor expression and
signaling: novel strategies for antimetastatic therapy.
AB - The receptor for the type 1 insulin-like growth factor (IGF-1R) plays a critical
role in the acquisition of the malignant phenotype. Using a highly metastatic
murine lung carcinoma model, it was demonstrated that this receptor regulates
several cellular functions that can impact on the metastatic potential of the
cells, including cellular proliferation, anchorage-independent growth, cell
migration, and invasion. The tumor model was used to develop several strategies
for altering receptor expression and function as means of abrogating the
metastatic potential of the cells. They include stable expression in the tumor
cells of IGF-1R antisense RNA and dominant negative receptor mutants in which
tyrosines in the kinase domain were substituted with phenylalanine. In addition,
a novel strategy was used based on altering post ligand-binding receptor
turnover. This led to inhibition of receptor re-expression and signaling and
resulted in increased tumor cell apoptosis. When combined with the development of
viral vectors designed to deliver genetic information with high efficiency, these
strategies could form the basis for development of highly specific,
antimetastatic therapy in tumors with known IGF-IR involvement.
PMID- 11007948
TI - Nuclear factor-kappa B activation and innate immune response in microbial
pathogen infection.
AB - Human pathogenic microorganisms have developed a variety of strategies to infect
the host organism successfully, whereas the host has evolved a series of defense
mechanisms. In most cases, the epithelial cell layer represents the first barrier
for the bacterial pathogen and triggers the innate and inflammatory responses in
the host. Epithelial cells release proinflammatory mediators including cytokines
and chemokines, leading to the subsequent attraction of monocytes/macrophages.
Therefore, epithelial cells represent an immediate-early warning system in the
host organism. Subsequent to the colonization of the epithelial layer, invasive
microbial pathogens often induce an acute inflammatory response, which functions
to activate residential macrophages and recruits blood leukocytes to the site of
infection. Distinct receptors of the Toll family on the cell surface of immune
cells mediate antibacterial responses in mammals as well as in Drosophila. One of
the most important cellular factors involved in the regulation of the host innate
antimicrobial response is the immediate-early response transcription factor
nuclear factor (NF)-kappa B. Microbial pathogens activate cellular signal
transduction pathways that induce NF-kappa B activation, but pathogens also find
ways to overcome the innate immune response through active manipulation of the NF
kappa B signal transduction pathways. Exploration of the mechanisms that
influence NF-kappa B activity could contribute to a better understanding of the
molecular pathogenesis of microbial infections and could be important for
potential therapeutic intervention that may be relevant in a wide variety of
inflammatory diseases.
PMID- 11007949
TI - Integrin-linked kinase (ILK): a "hot" therapeutic target.
AB - Integrin-mediated cell adhesion is known to regulate gene expression through the
activation of transcription factors. We have recently revealed that these
activations are mediated through integrin-linked kinase (ILK). ILK is an ankyrin
repeat-containing serine-threonine protein kinase that can interact directly with
the cytoplasmic domain of the beta1 and beta3 integrin subunits and whose kinase
activity is modulated by cell-extracellular matrix interactions. We have shown
that ILK overexpression results in the translocation of beta-catenin to the
nucleus, which then forms a complex formation with the lymphoid enhancer binding
factor 1 (LEF-1) transcription factor, subsequently activating the
transcriptional activity of promoters containing LEF-1 response elements. ILK
phosphorylates the glycogen synthase kinase-3 (GSK-3), which inhibits GSK-3
activity. We have demonstrated that ILK stimulates activator protein-1
transcriptional activity through GSK-3 and the subsequent regulation of the c-Jun
DNA interaction. ILK also phosphorylates protein kinase B (PKB/Akt) and
stimulates its activity. We have shown that ILK is an upstream effector of the
phosphatidylinositol 3-kinase-dependent regulation of PKB/Akt. ILK has been shown
to phosphorylate PKB/Akt on Ser-473 in vitro and in vivo. Our results clearly
indicate that ILK is a key element in the regulation of integrin signaling as
well as growth factor and Wnt signaling pathways. PTEN (phosphatase and tensin
homolog detected on chromosome 10) is a tumor suppressor gene located on
chromosome 10q23 that encodes a protein and phospholipid phosphatase. It is now
estimated that inactivation mutants of PTEN exist in 60% of all forms of solid
tumors. Loss of expression or mutational inactivation of PTEN leads to the
constitutive activation of PKB/Akt via enhanced phosphorylation of Thr-308 and
Ser-473. We have demonstrated that the activity of ILK is constitutively elevated
in PTEN mutant cells. A small molecule ILK inhibitor suppresses the
phosphorylation of PKB at the Ser-473 but not the Thr-308 site in the PTEN mutant
cells. These results indicate that inhibition of ILK may be of significant value
in solid tumor therapy.
PMID- 11007950
TI - Gene regulation of heme oxygenase-1 as a therapeutic target.
AB - Heme oxygenase (HO)-1 is the inducible isoform of the rate-limiting enzyme of
heme degradation. HO regulates the cellular content of the pro-oxidant heme and
produces catabolites with physiological functions. HO-1 is induced by a host of
oxidative stress stimuli, and the activation of HO-1 gene expression is
considered to be an adaptive cellular response to survive exposure to
environmental stresses. Since overexpression of the HO-1 gene is also protective
against the deleterious effects of experimental injuries, the specific induction
of HO-1 by 'non-stressful' stimuli, eg. stimuli that are not associated with
oxidative stress, such as adenosine 3', 5'-cyclic monophosphate or cyclic
guanosine 3',5'-monophosphate, may have important clinical implications. This
review summarizes recent advances in the understanding of regulatory mechanisms
of HO-1 gene expression, in particular the role of various redox-dependent and
redox-independent signaling pathways. Models of experimental injuries are
highlighted in which specific overexpression of the HO-1 gene either by targeted
gene transfer or by pharmacological modulation has been demonstrated to provide
therapeutic effects.
PMID- 11007952
TI - A20 and A20-binding proteins as cellular inhibitors of nuclear factor-kappa B
dependent gene expression and apoptosis.
AB - Proper gene expression and cell growth are critical for the survival of all
organisms. Nuclear factor-kappa B (NF-kappa B)-dependent gene expression and
apoptosis play crucial roles in numerous cellular processes, and defects in their
regulation may contribute to a variety of diseases including inflammation and
cancer. Although there has recently been tremendous progress in our understanding
of the signaling pathways that lead to NF-kappa B activation and apoptosis,
signaling mechanisms that negatively regulate these processes are only partially
understood. This review deals with the zinc finger protein A20, which has been
characterized as a dual inhibitor of NF-kappa B activation and apoptosis. Its
inducible expression by a wide variety of stimuli, including cytokines such as
tumor necrosis factor, interleukin-1, and CD40, as well as bacterial and viral
products such as lipopolysaccharide, Epstein-Barr virus latent membrane protein
1, and human T-cell leukemia virus type I Tax, suggests that it is involved in
the negative feedback regulation of signaling. We will discuss the possible
underlying mechanisms, placing emphasis on the role of several A20-binding
proteins that have recently been described. Moreover, evidence is presented that
A20 and A20-binding proteins are potential novel therapeutic tools in the
treatment of a variety of diseases.
PMID- 11007951
TI - The transcriptional signature of dioxin in human hepatoma HepG2 cells.
AB - We have used a high density microarray hybridization approach to characterize the
transcriptional response of human hepatoma HepG2 cells to 2,3,7,8
tetrachlorodibenzo-p-dioxin (TCDD). We find that exposure to 10 nM TCDD for 8 hr
alters by at least a factor of 2.1 the expression of 310 known genes and of an
equivalent number of expressed sequence tags. Treatment with TCDD in the presence
of 20 microg/mL of cycloheximide blocked the effect on 202 of these genes,
allowing us to distinguish between primary effects of TCDD exposure, which take
place whether cycloheximide is present or not, and secondary effects, which are
blocked by inhibition of protein synthesis. Of the 310 known genes affected by
TCDD, 30 are up-regulated and 78 are down-regulated regardless of cycloheximide
treatment, and 84 are up-regulated and 118 are down-regulated only when protein
synthesis is not inhibited. Functional clustering of genes regulated by TCDD
reveals many potential physiological interactions that might shed light on the
multiple biological effects of this compound. Our results, however, suggest that
arriving at a sound understanding of the molecular mechanisms governing the
biological outcome of TCDD exposure promises to be orders of magnitude more
complicated than might have been previously imagined.
PMID- 11007953
TI - New insights into p53 regulation and gene therapy for cancer.
AB - Due to its critical involvement in cell cycle control and apoptotic signaling,
the transcription factor p53 has become the most important tumor suppressor
currently under investigation. TP53 is the most frequently mutated gene in human
cancers and is thought to play a crucial role in malignant transformation.
Therefore, p53 appears to be an appealing target for gene therapy. Adenoviral
based p53 gene transfection is now being introduced in large clinical trials.
Viral cell entry was found to be the rate-limiting step of gene delivery and thus
of therapeutic efficiency. Attachment of adenoviruses to the target cell surface
is mediated through the coxsackie-adenovirus receptor, and internalization is
achieved via interactions with integrins of the alpha v beta(3) and alpha v
beta(5) class. The assumption that the restitution of the p53-dependent apoptotic
pathway results in a higher responsiveness of solid tumors to cytostatic agents
remains a major matter of debate. Combinations of p53-based gene therapy with
other components involved in apoptosis, such as tumor necrosis factor-related
apoptosis-inducing ligand (TRAIL)/APO2L, or agents neutralizing tumor-promoting
antiapoptotic signals, such as humanized anti-growth factor antibodies, should
further improve the effectiveness of cancer treatment in the future.
PMID- 11007954
TI - Inhibitors of Ras signal transduction as antitumor agents.
AB - Anarchic cell proliferation, observed in some leukemia and in breast and ovarian
cancers, has been related to dysfunctioning of cytoplasmic or receptor tyrosine
kinase activities coupled to p21 Ras. The growth factor receptor-bound protein 2
(Grb2) adaptor when complexed with Sos (Son of sevenless), the exchange factor of
Ras, conveys the signal induced by tyrosine kinase-activated receptor to Ras by
recruiting Sos to the membrane, allowing activation of Ras. This review shows how
it is possible to stop the Ras-deregulated signaling pathway to obtain potential
antitumor agents. Grb2 protein is comprised of one SH2 surrounded by two SH3
domains and interacts by means of its Src homology (SH2) domain with
phosphotyrosine residues of target proteins such as the epidermal growth factor
(EGF) receptor or the Shc adaptor. By means of its SH3 domains, Grb2 recognizes
proline-rich sequences of Sos, leading to Ras activation. Inhibitors of SH2 and
SH3 domains were designed with the aim of interrupting Grb2 recognition. On the
one hand, using structural data and molecular modeling, peptide dimers or
"peptidimers", made up of two proline-rich sequences from Sos linked by an
optimized spacer, were developed. On the other, using the structure of the Grb2
SH2 domain complexed with a phosphotyrosine (pTyr)-containing peptide and
molecular modeling studies, a series of N-protected tripeptides containing two
phosphotyrosine or mimetic residues, with one pTyr sterically constrained, were
devised. These compounds show very high affinities for Grb2 in vitro. They have
been targeted into cells showing selective antiproliferative activity on tumor
cells. These results suggest that inhibiting SH2 or SH3 domains of signaling
proteins might provide antitumor agents.
PMID- 11007955
TI - Signaling angiogenesis via p42/p44 MAP kinase and hypoxia.
AB - Angiogenesis is associated with a number of pathological situations. In this
study, we have focused our attention on the role of p42/p44 MAP (mitogen
activated protein) kinases and hypoxia in the control of angiogenesis. We
demonstrate that p42/p44 MAP kinases play a pivotal role in angiogenesis by
exerting a determinant action at three levels: i) persistent activation of
p42/p44 MAP kinases abrogates apoptosis; ii) p42/p44 MAP kinase activity is
critical for controlling proliferation and growth arrest of confluent endothelial
cells; and iii) p42/p44 MAP kinases promote VEGF (vascular endothelial growth
factor) expression by activating its transcription via recruitment of the AP
2/Sp1 (activator protein-2) complex on the proximal region (-88/-66) of the VEGF
promoter and by direct phosphorylation of hypoxia-inducible factor 1 alpha (HIF-1
alpha). HIF-1 alpha plays a crucial role in the control of HIF-1 activity, which
mediates hypoxia-induced VEGF expression. We show that oxygen-regulated HIF-1
alpha protein levels are not affected by intracellular localization (nucleus
versus cytoplasm). Finally, we propose a model which suggests an autoregulatory
feedback mechanism controlling HIF-1 alpha and therefore HIF-1-dependent gene
expression.
PMID- 11007956
TI - Cyclin A2 transcriptional regulation: modulation of cell cycle control at the
G1/S transition by peripheral cues.
AB - Several types of cyclins have been identified and among these, cyclin A2 is
synthesized in somatic cells at the onset of DNA synthesis as well as during the
G2/M transition associated with cyclin-dependent protein kinases 1 and 2.
Modulation of cyclin A transcription is due to the interplay between a cell cycle
dependent periodic relief of a transcriptional repression and signals transduced
through adenosine 3',5'-cyclic monophosphate, transforming growth factor-beta,
and the integrin-mediated pathways. Using primary mouse embryonic fibroblasts
from embryos where the genes coding for the protein responsible for
susceptibility to retinoblastoma (pRB) and the related p107 and p130 proteins had
been individually inactivated, we showed that cyclin A is a functional target of
pRB-mediated cell cycle arrest. The factors involved are discussed.
PMID- 11007957
TI - Signal transduction by tumor necrosis factor and gene regulation of the
inflammatory cytokine interleukin-6.
AB - Interleukin (IL)-6 is a multifunctional cytokine that can be induced by a
plethora of chemical or physiological compounds, including the inflammatory
cytokines tumor necrosis factor (TNF) and IL-1. The molecule TNF has a trimeric
configuration and thus binds to membrane-bound, cellular receptors to initiate
cell death mechanisms and signaling pathways leading to gene induction.
Previously, we showed that induced clustering of the intracellular domains of the
p55 TNF receptor, or of their respective 'death domains' only, is sufficient to
activate the nuclear factor kappa B (NF-kappa B) and several mitogen-activated
protein kinase (MAPK) pathways. NF-kappa B is the exclusive transcription factor
for induction of the IL-6 gene in response to TNF and functions as the final
trigger to activate a multiprotein complex, a so-called 'enhanceosome', at the
level of the IL-6 promoter. Furthermore, the enhanceosome displays histone
acetylation activity, which turned out to be essential for IL-6 gene activation
via NF-kappa B. However, activation of NF-kappa B alone is not sufficient for IL
6 gene induction in response to TNF, as inhibition of the coactivated
extracellular signal-regulated kinase and p38 MAPK pathways blocks TNF-mediated
gene expression. Nevertheless, the transactivating NF-kappa B subunit p65 is not
a direct target of MAPK phosphorylation. Thus, we postulated that other
components of the enhanceosome complex are sensitive to MAPK cascades and found
that MAPK activity is unequivocally linked to the histone acetylation capacity of
the enhanceosome to stimulate gene expression in response to TNF. In contrast,
glucocorticoid repression of TNF-driven IL-6 gene expression does not depend on
abrogation of histone acetyltransferase activity, but originates from
interference of the liganded glucocorticoid receptor with the contacts between NF
kappa B p65 and the promoter configuration around the TATA box.
PMID- 11007958
TI - The promyelocytic (PML) nuclear compartment and transcription control.
AB - Wild-type promyelocytic leukemia (PML) protein and an increasingly documented
number of cellular proteins are localized within discrete nuclear structures
known as PML nuclear bodies or PODs (potential oncogenic domains). Even though
POD function remains elusive, the integrity, topology, and molecular composition
of these nuclear compartments have been associated with certain human diseases,
including cancer, autoimmunity, neurodegenerative disorders, and viral
propagation. At the molecular level, PML protein has been shown to be a
coactivator of nuclear hormone receptors, whereas its oncogenic counterpart PML
retinoic acid receptor alpha, which promotes POD disaggregation, has been found
to activate activator protein-1 transcription in a retinoic acid-dependent
manner. Recently, we demonstrated that the CREB-binding protein (CBP) associates
with PML protein in vitro and is recruited to the PODs in vivo in a signal
dependent manner. In exploring the consequence of this association, we proposed
that POD nuclear bodies are regulatory cellular domains where proteins such as
the CBP and CBP-interacting molecules may be activated or inactivated to
coordinate signal-activated cellular response. This paper discusses the
association of PML nuclear bodies with transcription control and underscores the
pharmacological aspects of such an observation.
PMID- 11007959
TI - Nuclear tyrosine phosphorylation: the beginning of a map.
AB - Tyrosine phosphorylation is usually associated with cytoplasmic events. Yet, over
the years, many reports have accumulated on tyrosine phosphorylation of
individual molecules in the nucleus, and several tyrosine kinases and
phosphatases have been found to be at least partially nuclear. The question
arises as to whether nuclear tyrosine phosphorylation represents a collection of
loose ends of events originating in the cytoplasm or if there may be intranuclear
signaling circuits relying on tyrosine phosphorylation to regulate specific
processes. The recent discovery of a mechanism causing nuclear tyrosine
phosphorylation has prompted us to review the cumulative evidence for nuclear
tyrosine phosphorylation pathways and their possible role. While we found that no
complex nuclear function has yet been shown to rely upon intranuclear tyrosine
phosphorylation in an unambiguous fashion, we found a very high number of
compelling observations on individual molecules that suggest underlying networks
linking individual events. A systematic proteomics approach to nuclear tyrosine
phosphorylation should help chart possible interaction pathways.
PMID- 11007960
TI - Role of conformational alteration in the epidermal growth factor receptor (EGFR)
function.
AB - This mini-review addresses the effect of glycosylation and phosphorylation on the
conformational alterations of the epidermal growth factor receptor (EGFR). Based
on studies with full-length and truncated EGFRs, we propose a model to suggest
that receptor-receptor self-association, which occurs in the truncated receptor
and depends on core glycosylation, is prevented in intact receptor by a certain
extracellular domain and that the function of the ligand is to remove the
negative constraint. We also propose, based on works with a conformation-specific
antibody directed to an unphosphorylated peptide, that the interactions among
negatively charged phosphotyrosine residues in the receptor molecule result in
bringing two epitopes separated by a long stretch of amino acids close to each
other to form an antibody-binding site. The implications of these
posttranslational modifications on receptor functions are also discussed in this
article.
PMID- 11007961
TI - Type 2A protein phosphatase, the complex regulator of numerous signaling
pathways.
AB - Type 2A protein phosphatase (PP2A) comprises a diverse family of phosphoserine-
and phosphothreonine-specific enzymes ubiquitously expressed in eukaryotic cells.
Common to all forms of PP2A is a catalytic subunit (PP2Ac) which can form two
distinct complexes, one with a structural subunit termed PR65/A and another with
an alpha4 protein. The PR65/A-PP2Ac dimer may further associate with a regulatory
subunit and form a trimeric holoenzyme. To date, three distinct families of
regulatory subunits, which control substrate selectivity and phosphatase activity
and target PP2A holoenzymes to their substrates, have been identified. Other
molecular mechanisms that regulate PP2Ac function include phosphorylation,
carboxyl methylation, inhibition by intracellular protein inhibitors (I(1)(PP2A)
and I(2)(PP2A)), and stimulation by ceramide. PP2A dephosphorylates many proteins
in vitro, but in vivo protein kinases and transcription factors appear to
represent two major sets of substrates. Several natural compounds can inhibit
PP2A activity and are used to study its function. Mutations in genes encoding
PR65/A subunits have been identified in several different human cancers and the
PP2A inhibitor, termed fostriecin, is being tested as an anticancer drug. Thus, a
more thorough understanding of PP2A structure and function may lead to the
development of novel strategies against human diseases.
PMID- 11007962
TI - Phosphorylation of the cap-binding protein eIF4E by the MAPK-activated protein
kinase Mnk1.
AB - The purpose of this review is to summarize recent experimental data describing
the regulation of the phosphorylation of eIF4E, the cap-binding protein, by the
MAPK-activated protein kinase Mnk1. Mnk1 does not interact directly with eIF4E,
but uses a docking site in eIF4G, a partner of eIF4E. Consequently, control of
eIF4E phosphorylation may not strictly depend on changes in Mnk1 activity. The
possibility that integrity of the eIF4E/eIF4G/Mnk1 complex also impinges upon
eIF4E phosphorylation is discussed.
PMID- 11007963
TI - Role of the peroxisome proliferator-activated receptors (PPAR) in
atherosclerosis.
AB - Peroxisome proliferator-activated receptors (PPAR) are ligand-activated
transcription factors which form a subfamily of the nuclear receptor gene family.
PPAR activators have effects on both metabolic risk factors and on vascular
inflammation related to atherosclerosis. PPAR have profound effects on the
metabolism of lipoproteins and fatty acids. PPAR alpha binds hypolipidemic
fibrates, whereas PPAR gamma has a high affinity for antidiabetic glitazones.
Both PPAR are activated by fatty acids and their derivatives. Activation of PPAR
alpha increases the catabolism of fatty acids at several levels. In the liver, it
increases uptake of fatty acids and activates their beta-oxidation. The effects
that PPAR alpha exerts on triglyceride-rich lipoproteins is due to their
stimulation of lipoprotein lipase and repression of apolipoprotein CIII
expression, while the effects on high-density lipoproteins depend upon the
regulation of apolipoproteins AI and AII. PPAR gamma has profound effects on the
differentiation and function of adipose tissue, where it is highly expressed.
PPAR are also expressed in atherosclerotic lesions. PPAR are present in vascular
endothelial cells, smooth muscle cells, monocytes, and monocyte-derived
macrophages. Via negative regulation of nuclear factor-kappa B and activator
protein-1 signalling pathways, PPAR alpha inhibits expression of inflammatory
genes, such as interleukin-6, cyclooxygenase-2, and endothelin-1. Furthermore,
PPAR alpha inhibits expression of monocyte-recruiting proteins such as vascular
cell adhesion molecule (VCAM)-1 and induces apoptosis in monocyte-derived
macrophages. PPAR gamma activation in macrophages and foam cells inhibits the
expression of activated genes such as inducible nitric oxide synthase, matrix
metalloproteinase-9 and scavenger receptor A. PPAR gamma may also affect the
recruitment of monocytes in atherosclerotic lesions as it is involved in the
expression of VCAM-1 and intracellular adhesion molecule-1 in vascular
endothelial cells. The involvement of PPAR in atherosclerosis, a disease with a
chronic inflammatory character, suggests that they may play a role in other
inflammatory-related diseases as well.
PMID- 11007964
TI - Geranylgeranylated RhoB is sufficient to mediate tissue-specific suppression of
Akt kinase activity by farnesyltransferase inhibitors.
AB - Farnesyltransferase inhibitors (FTIs) induce apoptosis by elevating the levels of
geranylgeranylated RhoB (RhoB-GG) in cells. However, the mechanism by which RhoB
GG acts is unclear. Here we report that RhoB-GG is sufficient to mediate the
suppressive effects of FTIs on the activity of the survival kinase Akt-1 in
epithelial cells. This mechanism is tissue-specific insofar as it does not
operate in fibroblasts. We discuss how the cell survival functions of RhoB and
Akt may be linked biochemically in certain cell types.
PMID- 11007965
TI - AMP-activated protein kinase counteracted the inhibitory effect of glucose on the
phosphoenolpyruvate carboxykinase gene expression in rat hepatocytes.
AB - The effect of AMP-activated protein kinase (AMPK) in the regulation of the
phosphoenolpyruvate carboxykinase (PEPCK) gene expression was studied in isolated
rat hepatocytes. Activation of AMPK by AICAR counteracted the inhibitory effect
of glucose on the PEPCK gene expression, both at the mRNA and the transcriptional
levels. It is proposed that a target for AMPK is involved in the inhibitory
effect of glucose on PEPCK gene transcription.
PMID- 11007966
TI - Desethylamiodarone interferes with the binding of co-activator GRIP-1 to the beta
1-thyroid hormone receptor.
AB - Ligand binding to the thyroid hormone nuclear receptor beta1 (TRbeta(1)) is
inhibited by desethylamiodarone (DEA), the major metabolite of the widely used
anti-arrhythmic drug amiodarone. Gene expression of thyroid hormone
(triiodothyronine, T(3))-regulated genes can therefore be affected by amiodarone
due to less ligand binding to the receptor. Previous studies have indicated the
possibility of still other explanations for the inhibitory effects of amiodarone
on T(3)-dependent gene expression, probably via interference with receptor/co
activator and co-repressor complex. The binding site of DEA is postulated to be
on the outside surface of the receptor protein overlapping the regions where co
activator and co-repressor bind. Here we show the effect of a drug metabolite on
the interaction of TRbeta(1) with the co-activator GRIP-1 (glucocorticoid
receptor interacting protein-1). The T(3)-dependent binding of GRIP-1 to the
TRbeta(1) is disrupted by DEA. A DEA dose experiment showed that the drug
metabolite acts like an antagonist under 'normal' conditions (at 10(-7) M T(3)
and 5x10(-6)-->10(-3) M DEA), but as an agonist under extreme conditions (at 0
and 10(-9) M T(3) and >10(-4) M DEA). To our knowledge, these results show for
the first time that a metabolite of a drug which was not devised for this purpose
can interfere with nuclear receptor/co-activator interaction.
PMID- 11007967
TI - A novel role for protein phosphatase 2A in the dopaminergic regulation of Na,K
ATPase.
AB - Stimulation of dopaminergic type 1 (D(1)) receptors increases lung edema
clearance by regulating Na,K-ATPase function in the alveolar epithelium. We
studied the role of serine/threonine protein phosphatases in the Na,K-ATPase
regulation by D(1) agonists in A549 cells. We found that low doses of the type
1/2A protein phosphatase inhibitor okadaic acid as well as SV40 small t antigen
transiently transfected into A549 cells prevented the D(1) agonist-induced
increase in Na,K-ATPase activity and translocation from intracellular pools to
the plasma membrane. This was associated with a rapid and transient increase in
protein phosphatase 2A activity. We conclude that D(1) stimulation regulates Na,K
ATPase activity by promoting recruitment of Na,K-ATPases from intracellular pools
into the basolateral membranes of A549 cells via a type 2A protein phosphatase.
PMID- 11007969
TI - Elevated expression of membrane type 1 metalloproteinase (MT1-MMP) in reactive
astrocytes following neurodegeneration in mouse central nervous system.
AB - Reactive astrocytes occurring in response to neurodegeneration are thought to
play an important role in neuronal regeneration by upregulating the expression of
extracellular matrix (ECM) components as well as the ECM degrading
metalloproteinases (MMPs). We examined the mRNA levels and cellular distribution
of membrane type matrix metalloproteinase 1 (MT1-MMP) and tissue inhibitors 1-4
of MMPs (TIMPs) in brain stem and spinal cord of wobbler (WR) mutant mice
affected by progressive neurodegeneration and astrogliosis. MT1-MMP, TIMP-1 and
TIMP-3 mRNA levels were elevated, whereas TIMP-2 and TIMP-4 expression was not
affected. MT1-MMP was expressed in reactive astrocytes of WR. In primary
astrocyte cultures, MT1-MMP mRNA was upregulated by exogeneous tumor necrosis
factor alpha. Increased plasma membrane and secreted MMP activities were found in
primary WR astrocytes.
PMID- 11007968
TI - Functional involvement of a deoxy-D-xylulose 5-phosphate reductoisomerase gene
harboring locus of Synechococcus leopoliensis in isoprenoid biosynthesis.
AB - The present work aimed to proof the functionality of the non-mevalonate pathway
in cyanobacteria. It was intended to isolate the 1-deoxy-D-xylulose 5-phosphate
(DXP) reductoisomerase gene (dxr), as this gene encodes the enzyme which
catalyzes a pathway-specific, indicative step of this pathway. For this purpose,
a segment of dxr was amplified from Synechococcus leopoliensis SAUG 1402-1 DNA
via PCR using oligonucleotides for conserved regions. Subsequent hybridization
screening of a genomic cosmid library of S. leopoliensis with the PCR segment led
to the identification of a 26. 5 kbp locus on which a dxr homologous gene and two
adjacent open reading frames organized in one operon were localized by DNA
sequencing. The functionality of the gene was demonstrated expressing the gene in
Escherichia coli and using the purified gene product in a photometrical NADPH
dependent test based on the substrate DXP generating system. While the content of
one of the central intermediates of the isoprenoid biosynthesis (dimethylallyl
diphosphate=DMADP) was significantly (P=0.001) increased in E. coli cells
overexpressing the DXP synthase gene (dxs) of S. leopoliensis, overexpression of
dxr does not lead to an elevated DMADP level. Since even in strains harboring an
expression fusion of dxs the additional overexpression of dxr does not influence
the DMADP content, it is concluded that Dxs but not Dxr catalyzes a rate limiting
step of the non-mevalonate isoprenoid biosynthesis.
PMID- 11007970
TI - Greater diversity than previously thought of chromaffin cell Ca2+ channels,
derived from mRNA identification studies.
AB - Using reverse transcription followed by PCR amplification (RT-PCR), we have
identified multiple messenger RNAs encoding for the neuronal pore-forming Ca(2+)
channel subunits alpha(1A) (P/Q channel), alpha(1B) (N channel), alpha(1D)
(neuronal/endocrine L channel), alpha(1E) (R channel), alpha(1G-H) (T channel)
and alpha(1S) (skeletal muscle L channel) in bovine chromaffin cells. mRNAs for
the auxiliary beta(2), beta(3), beta(4), alpha(2)/delta and gamma(2) subunits
were also identified. In agreement with these molecular data, perforated patch
clamp recordings of whole-cell Ca(2+) currents reveal the existence of functional
R-type Ca(2+) channels in these cells that were previously undetected with other
techniques. Our results provide a molecular frame for a much wider functional
diversity of Ca(2+) channels in chromaffin cells than that previously established
using pharmacological and electrophysiological approaches.
PMID- 11007971
TI - Inositol(1,4,5)trisphosphate production in plant cells: an early response to
salinity and hyperosmotic stress.
AB - Salinity and hyperosmotic stress are environmental factors that severely affect
the growth and development of plants. Adaptation to these stresses is known to be
a complex multistep process, but a rise in cytoplasmic Ca(2+) and increased
polyphosphoinositide turnover have now been identified as being amongst the early
events leading to the development of tolerance. To determine whether a causal
link exists between these two events we have investigated the effects of several
salts and osmotic agents on levels of inositol(1, 4,5)trisphosphate
(Ins(1,4,5)P(3)) in plant cells. Our data show that salts as well as osmotic
agents induce a rapid and up to 15-fold increase in cellular Ins(1,4,5)P(3)
levels. The increase in Ins(1,4,5)P(3) occurs in a dose-dependent manner and
levels remain elevated for at least 10 min. These data indicate that increased
Ins(1,4,5)P(3) production is a common response to salt and hyperosmotic stresses
in plants and that it may play an important role in the processes leading to
stress tolerance.
PMID- 11007972
TI - Control of interleukin-18 secretion by dendritic cells: role of calcium influxes.
AB - Here we show that dendritic cells accumulate the precursor form of the leaderless
secretory protein interleukin-18 (pro-interleukin-18) in the cell cytosol and in
organelles co-fractionating with endolysosomes. Upon antigen specific contact
with T lymphocytes, particulated pro-interleukin-18 decreases rapidly, and the
cytokine appears extracellularly, suggesting that exocytosis of pro-interleukin
18-containing organelles is induced. Exocytosis of secretory lysosomes is
modulated by calcium: in agreement with this, calcium influx results in secretion
of pro-interleukin-18. In turn, pro-interleukin-18 secretion induced by T cells
is prevented by the calcium channel blocker nifedipine. Our results demonstrate a
novel, calcium-mediated mechanism of post-translational regulation of secretion
for interleukin-18, that allows a fast release of the cytokine.
PMID- 11007973
TI - Structural diversity of human class II histocompatibility molecules induced by
peptide ligands.
AB - SDS-PAGE analyses of stable HLA-DR1 complexes indicate that the binding of T cell
epitopes can lead to multiple conformational variants. Whereas short T epitopes
(<14-mer) induce complexes with apparent MW ranging from 47 to 57 kDa, longer
peptides form generally high mobility complexes (44-45 kDa). The generation of
HLA-DR1 conformational variants appears dependent on core peptide residues
fitting inside the groove but can additionally be attributed to the presence of N
and C-terminal flanking residues (PFRs) acting as a complementary mechanism.
These PFRs can jointly affect major histocompatibility complex class II
conformation and stability, supporting the existence of alternative contacts at a
distance from the classical binding site.
PMID- 11007974
TI - Coordinate expression of Ca2+-ATPase slow-twitch isoform and of beta calmodulin
dependent protein kinase in phospholamban-deficient sarcoplasmic reticulum of
rabbit masseter muscle.
AB - Modulation of sarcoplasmic reticulum (SR) Ca(2+) transport by endogenous
calmodulin-dependent protein kinase II (CaM K II) involves covalent changes of
regulatory protein phospholamban (PLB), as a common, but not the only mechanism,
in limb slow-twitch muscles of certain mammalian species, such as the rabbit.
Here, using immunofluorescent techniques in situ, and biochemical and
immunological methods on the isolated SR, we have demonstrated that rabbit
masseter, a muscle with a distinct embryological origin, lacks PLB. Accommodating
embryological heterogeneity in the paradigm of neural-dependent expression of
specific isogenes in skeletal muscle fibers, our results provide novel evidence
for the differential expression in the SR of 72 kDa beta components of CaM K II,
together with the expression of a slow-twitch sarcoendoplasmic reticulum Ca(2+)
ATPase isoform, both in limb muscle and in the masseter.
PMID- 11007975
TI - Identification of further important residues within the Glut4 carboxy-terminal
tail which regulate subcellular trafficking.
AB - The insulin-responsive glucose transporter, Glut4, exhibits a unique subcellular
distribution such that in the absence of insulin >95% of the protein is stored
within intracellular membranes. In response to insulin, Glut4 exhibits a large
mobilisation to the plasma membrane. Studies of the amino acid motifs which
regulate the unique trafficking of Glut4 have identified several key residues
within the soluble cytoplasmic N- and C-terminal domains of Glut4. Of particular
note is a Leu-498Leu-499 motif within the C-terminal domain that has been
proposed to regulate both internalisation from the plasma membrane and sorting to
an insulin-sensitive compartment. In this study, we have examined the role of the
adjacent amino acids (Glu-491, Gln-492 and Glu-493) by their sequential
replacement with Ala. Our results are consistent with the notion that Glu-491 and
Glu-493 play an important role in the sub-endosomal trafficking of Glut4, as
substitution of these residues with Ala results in increased levels of these
proteins at the cell surface, reduced insulin-stimulated translocation and
increased susceptibility to endosomal ablation. These residues, together with
other identified sequences within the C-terminus of Glut4, are likely to be
crucial targeting elements that regulate Glut4 subcellular distribution.
PMID- 11007976
TI - Molecular identification of a glucose transporter from fish muscle.
AB - In mammals and birds, several isoforms of facilitative glucose transporters have
been identified (GLUT1-4), but no information is available regarding the
molecules involved in glucose transport in other vertebrates. Here we report the
cloning of a GLUT molecule from fish muscle with high sequence homology to GLUT4
and containing features characteristic of a functional GLUT. Fish GLUT is
expressed predominantly in skeletal muscle, kidney and gill, which are tissues
with known high glucose utilization. These results indicate that fish GLUT is
structurally, and perhaps functionally, similar to the other known GLUTs
expressed in muscle in mammalian and avian species.
PMID- 11007977
TI - Selective stimulation of somatostatin receptor subtypes: differential effects on
Ras/MAP kinase pathway and cell proliferation in human neuroblastoma cells.
AB - In previous studies we have showed that somatostatin (SST) inhibits cell
division, mitogen-activated protein (MAP) kinase and Ras activity in the human
neuroblastoma cell line SY5Y. In the present study, we have assessed the role of
a series of SST analogs, three of which were selective for SSTR1, SSTR2 or SSTR5,
in these cellular events. All the analogs inhibited forskolin-induced cAMP
accumulation. Selective stimulation of SSTR1 or SSTR2 but not of SSTR5 inhibited
platelet-derived growth factor (PDGF)-induced [(3)H]thymidine incorporation. The
three analogs inhibited PDGF-stimulated MAP kinase activity, at least at an early
time. In contrast, none of the analogs used individually was able to inhibit PDGF
stimulated Ras activity. A combined stimulation of SSTR2 and SSTR5 was necessary
to obtain a significant inhibitory effect, suggesting the possibility of receptor
heterodimerization. These results indicate that SST inhibition of Ras and MAP
kinase activities takes place via different pathways and that SST inhibition of
PDGF-induced cell proliferation occurs via a Ras-independent pathway.
PMID- 11007978
TI - Cleavage of yeast tRNAPhe with complementary oligonucleotide conjugated to a
small ribonuclease mimic.
AB - An oligonucleotide conjugate bearing a chemical construct mimicking the catalytic
center of ribonuclease A has been designed and studied. The conjugate efficiently
cleaves yeast tRNAPhe at a single site adjacent to the target complementary
sequence.
PMID- 11007979
TI - Interaction of sigma 70 with Escherichia coli RNA polymerase core enzyme studied
by surface plasmon resonance.
AB - The interaction between the core form of bacterial RNA polymerases and sigma
factors is essential for specific promoter recognition, and for coordinating the
expression of different sets of genes in response to varying cellular needs. The
interaction between Escherichia coli core RNA polymerase and sigma 70 has been
investigated by surface plasmon resonance. The His-tagged form of sigma 70 factor
was immobilised on a Ni2+-NTA chip for monitoring its interaction with core
polymerase. The binding constant for the interaction was found to be 1.9x10(-7)
M, and the dissociation rate constant for release of sigma from core, in the
absence of DNA or transcription, was 4x10(-3) s(-1), corresponding to a half-life
of about 200 s.
PMID- 11007980
TI - MECP2 mutation in male patients with non-specific X-linked mental retardation.
AB - In contrast to the preponderance of affected males in families with X-linked
mental retardation, Rett syndrome (RTT) is a neurological disorder occurring
almost exclusively in females. The near complete absence of affected males in RTT
families has been explained by the lethal effect of an X-linked gene mutation in
hemizygous affected males. We report here on a novel mutation (A140V) in the
MECP2 gene detected in one female with mild mental retardation. In a family
study, the A140V mutation was found to segregate in the affected daughter and in
four adult sons with severe mental retardation. These results indicate that MECP2
mutations are not necessarily lethal in males and that they can be causative of
non-specific X-linked mental retardation.
PMID- 11007981
TI - Characterization of the active site thiol group of rhinovirus 2A proteinase.
AB - Picornains 2A are cysteine proteases of picornaviruses, a virus family containing
several human and animal pathogens. The pH dependencies of the alkylations of
picornain 2A of rhinovirus type 2 with iodoacetamide and iodoacetate show two
reactive thiol forms, namely the free thiolate ion at high pH and an imidazole
assisted thiol group at low pH. Kinetic deuterium isotope effects do not support
general base catalysis by the imidazole group, but rather the existence of a
catalytically competent thiolate-imidazolium ion-pair. The nature of the ion-pair
differs from that of papain, the paradigm of cysteine proteases. The ion-pair is
confined to the same, unusually narrow pH range in which the enzyme exhibits
catalytic activity.
PMID- 11007983
TI - Nitric oxide synthases catalyze superoxide formation.
PMID- 11007982
TI - Functional identification of the glycerol permease activity of Arabidopsis
thaliana NLM1 and NLM2 proteins by heterologous expression in Saccharomyces
cerevisiae.
AB - NLM proteins (NOD26-like major intrinsic proteins) from plants contain amino acid
sequence signatures which can be found in aquaporins including plant plasma
membrane intrinsic proteins and tonoplast intrinsic proteins and glycerol
permeases such as the Escherichia coli GlpF and the yeast FPS1 proteins.
Heterologous expression of two members of the NLM subgroup from Arabidopsis
thaliana (AtNLM1 and AtNLM2) in baker's yeast demonstrated the glycerol permease
activity in addition to the previously described aquaporin activity of AtNLM1.
The transport was non-saturable up to 100 mM extracellular glycerol
concentration. Longer-chain sugar alcohols did not compete with the transport of
radiolabelled glycerol and hexoses were also not transported through the pore.
PMID- 11007984
TI - Clonidine induces upper airway closure in awake goats.
AB - We examined the effects of the alpha(2)-adrenoceptor (alpha(2)-AR) agonist
clonidine on pressure-flow relationships in the upper airway. Inspired and
expired airflows, subglottic tracheal pressure (PTR), mask pressure and middle
pharyngeal constrictor (MPC) and diaphragm electromyogram (EMG) activities were
recorded in awake standing goats. Clonidine-induced central apneas were always
associated with continuous tonic activation of the MPC. Subglottic PTR during
expiration increased progressively in a dose-dependent manner after clonidine
administration. In all cases, positive subglottic PTR was maintained throughout
the duration of clonidine-induced apneas and was sufficient to retard or prevent
expiratory flow during early and mid-expiration indicating complete airway
closure. The effects of clonidine were reversed by selective alpha(2)-AR blockade
with SKF-86466. Central apneas after spontaneous augmented breaths (sighs) were
associated with continuous tonic activation of the MPC throughout the duration of
the prolonged TE intervals. However, subglottic PTR during expiration was not
significantly different from control breaths and there was no evidence of
increased expiratory airway resistance or delayed expiratory flow. We conclude
that continuous tonic activation of pharyngeal adductor muscles appears to be a
constant feature of central apnea in the awake goat independent of the initiating
cause of the apnea. However, our data suggest that MPC activation alone may not
be sufficient to cause complete closure of the upper airway during central apnea.
PMID- 11007986
TI - Developmental changes in cardio-respiratory responses to hypoxia and hypercapnia
in anesthetized low-birth-weight rats.
AB - The present study compared the developmental changes in the cardio-respiratory
responses to hypoxia and hypercapnia between full-term low-birth-weight (LBW) and
control rats during the postnatal period. The heart rate (HR), respiratory
frequency (fR) and amplitude (aR) were measured during hypoxia (10% O(2) for 10
min) and hypercapnia (5% CO(2) for 10 min) in rats aged 7, 14 and 21 days,
anesthetized with urethane. During hypoxia, HR was not significantly modified in
the younger rats of both groups. In the older rats, aged 14 and 21 days, HR was
markedly diminished, with a more pronounced decrease in LBW rats. The HR recovery
was never observed in the older LBW rats. The fR and aR showed an age-related
increase in both groups: a biphasic fR pattern observed on day 7 was replaced by
a sustained increase on days 14 and 21. In contrast to controls, LBW rats never
displayed a fR recovery during reoxygenation. In controls, aR shifted from a
biphasic pattern in the younger rats to a sustained increase in the older ones.
The LBW rats only displayed a decrease of aR in the younger, while in the older
ones, a transient and slight increase preceded this decrease. During hypercapnia,
the only significant difference detected between these two groups was that aR
increased in LBW rats to a greater extent than in controls on days 14 and 21.
Altogether, our results revealed a markedly attenuated cardio-respiratory
response to hypoxia in LBW rats, but no such effect in response to hypercapnia.
PMID- 11007985
TI - Changes in dopamine D(2)-receptor modulation of the hypoxic ventilatory response
with chronic hypoxia.
AB - Modulation of the hypoxic ventilatory response (HVR) by dopamine D(2)-receptors
(D(2)-R) in the carotid body (CB) and central nervous system (CNS) are
hypothesized to contribute to ventilatory acclimatization to hypoxia. We tested
this with blockade of D(2)-R in the CB or CNS in conscious rats after 0, 2 and 8
days of hypoxia. On day 0, CB D(2)-R blockade significantly increased VI and
frequency (fR) in hyperoxia (FI(O(2))=0.30), but not hypoxia (FI(O(2))=0.10). CNS
D(2)-R blockade significantly decreased fR in hypoxia only. On day 2, neither CB
nor CNS D(2)-R blockade affected VI or fR. On day 8, CB D(2)-R blockade
significantly increased hypoxic VI and fR. CNS D(2)-R blockade significantly
decreased hypoxic VI and fR. CB and CNS D(2)-R modulation of the HVR decreased
after 2 days of hypoxia, but reappeared after 8 days. Changes in the opposing
effects of CB and CNS D(2)-R on the HVR during chronic hypoxia cannot completely
explain ventilatory acclimatization in rats.
PMID- 11007987
TI - Characterizations of eupnea, apneusis and gasping in a perfused rat preparation.
AB - In vivo mammalian preparations can exhibit eupnea, apneusis and gasping. In vitro
mammalian preparations exhibit only a single invariant pattern, which appears
identical to gasping. We characterized the patterns of ventilatory activity of a
perfused heart-brainstem preparation of the juvenile rat. In this preparation,
phrenic activity has a 'ramp-like' rise similar to eupnea in vivo. Peak phrenic
activity declines and ultimately disappears in hypocapnia. In hypercapnia, both
frequency and peak of phrenic bursts increase. In hypoxia, such increases are
transient. The phrenic burst is terminated by electrical stimulation of the
pontile 'pneumotaxic center' and, as in apneusis, is prolonged by lesions in this
region. With severe hypoxia or ischemia, the 'ramp-like' phrenic activity is
replaced by the 'decrementing' pattern of gasping. Variables of phrenic activity
in gasping produced in hypoxia and ischemia are identical. We conclude that the
perfused juvenile rat preparation exhibits patterns of eupnea, apneusis and
gasping which are similar to in vivo mammalian preparations.
PMID- 11007988
TI - Sensitivities of eupnea and gasping to alterations in temperature of in vivo and
perfused rat preparations.
AB - Severe hypoxia or ischemia causes an alteration from eupnea to gasping. At body
temperatures approximating 37 degrees C in vivo, the frequency of gasping is much
less than that of eupnea. However in a perfused juvenile rat preparation, which
is maintained at 30-31 degrees C, the frequency of eupnea and gasping is the
same. We hypothesized that brainstem mechanisms responsible for the neurogenesis
of eupnea and gasping might have different sensitivities to alterations in
temperature. In both decerebrate adult rats in vivo and in a perfused juvenile
rat preparation, eupnea and gasping had different frequencies at rectal or
perfusate temperatures in excess of 34 degrees C, whereas, at lower temperatures,
eupnea and gasping had identical frequencies in both preparations. These findings
support the conclusion that different brainstem mechanisms underlie the
neurogenesis of eupnea and gasping. In addition, these findings have implications
for interpretation of results from in vitro mammalian preparations, which are
examined at temperatures at which the frequency of eupnea and gasping are
indistinguishable.
PMID- 11007989
TI - Estimation of diaphragm length in patients with severe chronic obstructive
pulmonary disease.
AB - In patients with advanced chronic obstructive pulmonary disease (COPD) diaphragm
function may be compromised because of reduced muscle fibre length. Diaphragm
length (L(Di)) can be estimated from measurements of transverse diameter of the
rib cage (D(Rc)) and the length of the zone of apposition (L(Zapp)) in healthy
subjects, but this method has not been validated in patients with COPD. Postero
anterior chest radiographs were obtained at total lung capacity (TLC), functional
residual capacity (FRC) and residual volume (RV) in nine male patients with
severe COPD (mean [S.D.]; FEV(1), 23 [6] %pred.; FRC, 199 [15] %pred.).
Radiographs taken at TLC were used to identify the lateral costal insertions of
the diaphragm (L(Zapp) assumed to approach zero at TLC). L(Di) was measured
directly and also estimated from measurements of L(Zapp) and D(Rc) using a
prediction equation derived from healthy subjects. The estimation of L(Di) was
highly accurate with an intraclass correlation coefficient of 0.93 and 95% CI of
approximately +/-8% of the true value. L(Di) decreased from 426 (64) mm at RV to
305 (31) mm at TLC. As there were only small and variable changes in D(Rc) across
the lung volume range, most of the L(Di) changes occurred in the zone of
apposition. Additional studies showed that measurements of L(Di) from PA and
lateral radiographs performed at different lung volumes were tightly correlated.
These results suggest that non-invasive measurements of L(Zapp) in the coronal
plane (e.g. using ultrasonography) and D(Rc) (e.g. using magnetometers) can be
used to provide an accurate estimate of L(Di) in COPD patients.
PMID- 11007990
TI - Arterial hypoxaemia in endurance athletes is greater during running than cycling.
AB - The effect of both training discipline and exercise modality on exercise-induced
hypoxaemia (EIH) was examined in seven runners and six cyclists during 5 min high
intensity treadmill and cycle exercise. There were no significant interactions
between training discipline, exercise modality and arterial P(O(2)) (Pa(O(2)))
when subject groups were considered separately but when pooled there were
significant differences between exercise modalities. After min 2 of exercise
arterial hydrogen ion concentration, minute ventilation, alveolar P(O(2))
(PA(O(2))) and Pa(O(2)) were all lower with treadmill running with the largest
differential for the latter occurring at min 5 (treadmill, 80.8+/-1.8; cycle,
90.2+/-2.5, mmHg, N=13, P< or = 0.05). At every min of exercise, the differences
in Pa(O(2)) between the ergometers were strongly associated with similar
differences in PA(O(2)) and alveolar to arterial P(O(2)) (PA(O(2))-Pa(O(2))). It
is concluded that the greater EIH with treadmill running is a consequence of the
combined effect of a reduced lactic acidosis-induced hyperventilation and greater
ventilation-perfusion inequality with this exercise mode.
PMID- 11007991
TI - Preface
PMID- 11007992
TI - Dinucleoside polyphosphates-friend or foe?
AB - Despite being known for over 30 years, the functions of the dinucleoside
polyphosphates, such as diadenosine 5',5"'-P(1), P(4)-tetraphosphate (Ap(4)A) and
diadenosine 5',5"'-P(1), P(3)-triphosphate (Ap(3)A), are still unclear. On the
one hand, they may have important signalling functions, both inside and outside
the cell (friend), while on the other hand, they may simply be the unavoidable by
products of certain biochemical reactions, which, if allowed to accumulate, would
be potentially toxic through their structural similarity to ATP and other
essential mononucleotides (foe). Here, the occurrence, synthesis, degradation,
and proposed functions of these compounds are briefly reviewed, along with some
new data and recent evidence supporting roles for Ap(3)A and Ap(4)A in the
cellular decision making processes leading to proliferation, quiescence,
differentiation, and apoptosis. Hypotheses are forwarded for the involvement of
Ap(4)A in the intra-S phase DNA damage checkpoint and for Ap(3)A and the pFhit
(fragile histidine triad gene product) protein in tumour suppression. It is
concluded that the roles of friend and foe are not incompatible, but are
distinguished by the concentration range of nucleotide achieved under different
circumstances.
PMID- 11007993
TI - Synthesis of dinucleoside polyphosphates catalyzed by firefly luciferase and
several ligases.
AB - The findings presented here originally arose from the suggestion that the
synthesis of dinucleoside polyphosphates (Np(n)N) may be a general process
involving enzyme ligases catalyzing the transfer of a nucleotidyl moiety via
nucleotidyl-containing intermediates, with release of pyrophosphate. Within this
context, the characteristics of the following enzymes are presented. Firefly
luciferase (EC 1.12. 13.7), an oxidoreductase with characteristics of a ligase,
synthesizes a variety of (di)nucleoside polyphosphates with four or more inner
phosphates. The discrepancy between the kinetics of light production and that of
Np(n)N synthesis led to the finding that E*L-AMP (L = dehydroluciferin), formed
from the E*LH(2)-AMP complex (LH(2) = luciferin) shortly after the onset of the
reaction, was the main intermediate in the synthesis of (di)nucleoside
polyphosphates. Acetyl-CoA synthetase (EC 6.2.1.1) and acyl-CoA synthetase (EC
6.2.1. 8) are ligases that synthesize p(4)A from ATP and P(3) and, to a lesser
extent, Np(n)N. T4 DNA ligase (EC 6.5.1.1) and T4 RNA ligase (EC 6.5.1.3)
catalyze the synthesis of Np(n)N through the formation of an E-AMP complex with
liberation of pyrophosphate. DNA is an inhibitor of the synthesis of Np(n)N and
conversely, P(3) or nucleoside triphosphates inhibit the ligation of a single
strand break in duplex DNA catalyzed by T4 DNA ligase, which could have
therapeutic implications. The synthesis of Np(n)N catalyzed by T4 RNA ligase is
inhibited by nucleoside 3'(2'),5'-bisphosphates. Reverse transcriptase (EC
2.7.7.49), although not a ligase, catalyzes, as reported by others, the synthesis
of Np(n)ddN in the process of removing a chain termination residue at the 3'-OH
end of a growing DNA chain.
PMID- 11007995
TI - Specific and nonspecific enzymes involved in the catabolism of mononucleoside and
dinucleoside polyphosphates.
AB - This review concerns enzymes that can degrade nucleoside 5'-tetra- and
pentaphosphates (p(4)N and p(5)N) and those that can degrade various dinucleoside
polyphosphates (Np(3-6)N'). Most of these enzymes are hydrolases, and they occur
in all types of organisms. Certain fungi and protozoa also possess specific
Np(n)N' phosphorylases. Specific p(4)N hydrolases have been demonstrated in
mammals and in plants. In yeast, p(4)N and p(5)N are hydrolyzed by
exopolyphosphatases. Among other hydrolases that can degrade these minor
mononucleotides are phosphatases, apyrase, and (asymmetrical) Np(4)N' hydrolase,
as well as the nonspecific adenylate deaminase. Np(n)N's are good substrates for
Type I phosphodiesterases and nucleotide pyrophosphatases, and diadenosine
polyphosphates are easily deaminated to diinosine polyphosphates by nonspecific
adenylate deaminases. Specific Np(3)N' hydrolases occur in both prokaryotes and
eukaryotes. Interestingly, the human fragile histidine triad (Fhit) tumor
suppressor protein appears to be a typical Np(3)N' hydrolase. Among the specific
Np(4)N' hydrolases are asymmetrically cleaving ones, which are typical of higher
eukaryotes, and symmetrically cleaving enzymes found in Physarum polycephalum and
in many bacteria. An enzyme that hydrolyzes both diadenosine tetraphosphate and
diadenosine triphosphate has been found in the fission yeast Schizosaccharomyces
pombe. Its amino acid sequence is similar to that of the human Fhit/Np(3)N'
hydrolase. Very recently, a typical (asymmetrical) Np(4)N' hydrolase has been
demonstrated for the first time in a bacterium-the pathogenic Bartonella
bacilliformis. Another novelty is the discovery of diadenosine 5', 5"'-P(1),P 6
hexaphosphate hydrolases in budding and fission yeasts and in mammalian cells.
These enzymes and the (asymmetrical) Np(4)N' hydrolases have the amino acid motif
typical of the MutT (or Nudix hydrolase) family. In contrast, the
Schizosaccharomyces pombe Ap(4)A/Ap(3)A hydrolase, the human Fhit protein, and
the yeast Np(n)N' phosphorylases belong to a superfamily GAFH, which includes the
histidine triad proteins.
PMID- 11007994
TI - Diadenosine polyphosphate receptors. from rat and guinea-pig brain to human
nervous system.
AB - Diadenosine polyphosphates are a family of naturally occurring nucleotidic
compounds present in secretory vesicles together with other chemical messengers.
The exocytotic release of these compounds permits them to stimulate receptors
termed "purinoceptors" or "ATP receptors." Purinoceptors for nucleotides are
named P2 in contrast with those sensitive to nucleosides (P1). P2 receptors are
further subdivided into metabotropic P2Y receptors, further divided into 5
subtypes, and ionotropic P2X receptors, with 7 different subtypes. Diadenosine
polyphosphates can activate recombinant P2Y(1), P2Y(2), and P2Y(4) and
recombinant homomeric P2X(1), P2X(2), P2X(3), P2X(4), and P2X(6). Heteromeric P2X
receptors change their sensitivity to diadenosine polyphosphates when co-assembly
between different subunits occurs. Diadenosine polyphosphates can activate
specific receptors termed dinucleotide receptors or P4 receptors, which are
insensitive to other nucleosides or nucleotides. The P4 receptor is a receptor
operated Ca(2)+ channel present in rat brain synaptic terminals, stimulated by
diadenosine pentaphosphate and diadenosine tetraphosphate. This receptor is
strongly modulated by protein kinases A and C and protein phosphatases. The
dinucleotide receptor is present in different brain areas, such as midbrain (in
rat and guinea-pig), cerebellum (in guinea-pig), and cortex (in human).
PMID- 11007996
TI - The role of adenosine in preconditioning.
AB - Preconditioning is a powerful form of (myocardial) protection that follows brief
sublethal ischemia. G-protein-coupled receptors constitute the trigger for
entrance to the preconditioned state. In conjunction with other receptors,
various membrane adenosine receptors play an important role in the transduction
of extracellular signals, leading to protection by preconditioning, lasting 1-3
hr. Adenosine A(1)- and A(3)-receptors mediate inhibition of adenylate cyclase
via a guanine nucleotide binding inhibitory protein (G(i/o)). A(2)-receptors
couple to a comparable stimulatory protein (G(s)). Adenosine receptors are
especially abundant in the central nervous system; in lesser numbers, they are
found in many tissues, including the heart. A(1)-receptors are located on
cardiomyocytes and vascular smooth muscle cells, A(2)-receptors on endothelial
and vascular smooth muscle cells, and A(3)-receptors on ventricular myocytes.
Ischemic preconditioning by endogenous adenosine takes place through A(1)- and
A(3)-receptors. A(2A/B)-receptor activation results in vasodilation. The
relevance of cellular mediators, such as 5'-nucleotidase, to generate adenosine
for preconditioning is controversial. In contrast, the role of protein kinase C
(PKC) is clearly established. Signals from different receptors converge at PKC,
reaching a threshold activation of the kinase necessary to induce protection.
Tyrosine and mitogen-activated protein kinases may play a role in addition to
PKC. The exact products downstream responsible for the memory of preconditioning
are elusive. A prime candidate for the end-effector of preconditioning is the
K(ATP) channel. Preconditioning with adenosine-receptor agonists offers the
possibility for treatment of coronary artery disease, but research in this field
is still in its infancy.
PMID- 11007997
TI - The adenosine-induced mechanism for the acquisition of ischemic tolerance in
primary rat neuronal cultures.
AB - Neurons can be preconditioned by various procedures to resist ischemic insult.
The preconditioning mechanism induced by adenosine ("the adenosine mechanism")
was characterized in primary rat neuronal cultures, employing a model of chemical
ischemia. The protective mechanism, initiated by activation of adenosine
receptors, consists of a signal transduction pathway, involving activation of
protein kinase C (PKC) and opening of ATP-sensitive potassium (K(ATP)) channels.
Direct activation (and inhibition) of PKC, as well as opening of K(ATP) channels,
also confers protection. The opening of the K(ATP) channels mediates the signal
activated by the adenosine receptors, and probably also that activated by PKC.
The acquired ischemic resistance lasts up to 5 days, depending on the activating
substance. The adenosine-activated cascade of events leading to ischemic
tolerance in neurons is similar to that operating in cardiomyocytes.
PMID- 11007998
TI - Tumor-promoting functions of adenosine.
AB - Tumor growth is a multifactorial process that, in addition to mutations leading
to dysregulated expression of oncogenes and tumor suppressive genes, requires
specific conditions that provide a supportive physiological environment at the
primary and metastatic sites of the disease. Adenosine is one of the factors
potentially contributing to tumor growth that thus far has not received adequate
attention, despite evidence for a broad range of cytoprotective, growth
promoting, and immunosuppressive activities. Adenosine accumulates in solid
tumors at high concentrations, and has been shown to stimulate tumor growth and
angiogenesis and to inhibit cytokine synthesis, adhesion of immune cells to the
endothelial wall, and the function of T-cells, macrophages, and natural killer
cells. However, the mechanisms whereby adenosine accumulates in cancer and the
specific effects that result from this accumulation are not well understood. This
article surveys the available evidence that supports an important role of
adenosine in cancer.
PMID- 11008000
TI - Phosphorylation of nucleosides and nucleoside analogs by mammalian nucleoside
monophosphate kinases.
AB - Nucleoside monophosphate kinases catalyze the reversible phosphotransferase
reaction between nucleoside triphosphates and monophosphates, i.e.,
monophosphates are converted to their corresponding diphosphate form. These
enzymes play an important role in the synthesis of nucleotides that are required
for a variety of cellular metabolic processes, as well as for RNA and DNA
synthesis. Human tissues contain a thymidylate kinase, a uridylate-cytidylate
kinase, five isozymes of adenylate kinase, and several guanylate kinases.
Nucleoside monophosphate kinases are also required for the pharmacological
activation of therapeutic nucleoside and nucleotide analogs. This overview is
focused on the substrate specificity, tissue distribution, and subcellular
location of the mammalian monophosphate kinases and their role in the activation
of nucleoside and nucleotide analogs.
PMID- 11007999
TI - Effect of antimetabolite drugs of nucleotide metabolism on the anti-human
immunodeficiency virus activity of nucleoside reverse transcriptase inhibitors.
AB - A number of attempts are currently underway to combine antimetabolite drugs of
nucleotide metabolism with a nucleoside reverse transcriptase inhibitor (NRTI)
targeting human immunodeficiency virus (HIV) to improve the antiviral efficacy of
the NRTIs and to better control HIV drug resistance. Hydroxyurea, a
ribonucleotide reductase inhibitor, is currently combined with the NRTI
didanosine (2',3'-dideoxyinosine) in clinical trials. However, other cellular
target enzymes, including thymidylate synthase, inosinate dehydrogenase, cytidine
5'-triphosphate synthetase, and other enzymes from the de novo nucleotide
biosynthesis pathway, can also be considered to potentiate the antiviral action
of NRTIs. The underlying reasons for the potentiation of the antiviral activity
of the NRTIs by antimetabolite drugs of nucleotide metabolism can be multiple.
Decreased endogenous 2'-deoxynucleoside-5'-triphosphate (dNTP) pools result in a
better competition of the NRTI (as its triphosphate derivative), with the dNTPs
for the virus-encoded reverse transcriptase to be recognized as a substrate for
the DNA polymerization reaction and subsequently to be incorporated into the
growing viral DNA chain. Also, an increased metabolism (phosphorylation) of the
NRTI by stimulatory enzyme feedback mechanisms may result in the production of
higher levels of NRTI triphosphate. Thus, higher intracellular ratios of NRTI
triphosphate/dNTP created by well-defined combinations of NRTIs and
antimetabolite drugs enable a more profound inhibitory effect of the NRTI against
the reverse transcriptase (and thus, against the virus) and a better suppression
of resistant (mutant) virus strains. A profound evaluation of this relatively new
concept in the clinical setting will reveal whether this approach will establish
a place in future treatment modalities of HIV infections.
PMID- 11008001
TI - Cyclic nucleotide analogs as biochemical tools and prospective drugs.
AB - Cyclic AMP (cAMP) and cyclic GMP (cGMP) are key second messengers involved in a
multitude of cellular events. From the wealth of synthetic analogs of cAMP and
cGMP, only a few have been explored with regard to their therapeutic potential.
Some of the first-generation cyclic nucleotide analogs were promising enough to
be tested as drugs, for instance N(6),O(2)'-dibutyryl-cAMP and 8-chloro-cAMP
(currently in clinical Phase II trials as an anticancer agent). Moreover, 8-bromo
and dibutyryl analogs of cAMP and cGMP have become standard tools for
investigations of biochemical and physiological signal transduction pathways. The
discovery of the Rp-diastereomers of adenosine 3',5'-cyclic monophosphorothioate
and guanosine 3',5'-cyclic monophosphorothioate as competitive inhibitors of cAMP
and cGMP-dependent protein kinases, as well as subsequent development of related
analogs, has proven very useful for studying the molecular basis of signal
transduction. These analogs exhibit a higher membrane permeability, increased
resistance against degradation, and improved target specificity. Furthermore,
better understanding of signaling pathways and ligand/protein interactions has
led to new therapeutic strategies. For instance, Rp-8-bromo-adenosine 3',5'
cyclic monophosphorothioate is employed against diseases of the immune system.
This review will focus mainly on recent developments in cyclic nucleotide-related
biochemical and pharmacological research, but also highlights some historical
findings in the field.
PMID- 11008002
TI - Basis for effective combination cancer chemotherapy with antimetabolites.
AB - Most current chemotherapy regimens for cancer consist of empirically designed
combinations, based on efficacy and lack of overlapping toxicity. In the
development of combinations, several aspects are often overlooked: (1) possible
metabolic and biological interactions between drugs, (2) scheduling, and (3)
different pharmacokinetic profiles. Antimetabolites are used widely in
chemotherapy combinations for treatment of various leukemias and solid tumors.
Ideally, the combination of two or more agents should be more effective than each
agent separately (synergism), although additive and even antagonistic
combinations may result in a higher therapeutic efficacy in the clinic. The
median-drug effect analysis method is one of the most widely used methods for in
vitro evaluation of combinations. Several examples of classical effective
antimetabolite-(anti)metabolite combinations are discussed, such as that of
methotrexate with 6-mercaptopurine or leucovorin in (childhood) leukemia and 5
fluorouracil (5FU) with leucovorin in colon cancer. More recent combinations
include treatment of acute-myeloid leukemia with fludarabine and
arabinosylcytosine. Other combinations, currently frequently used in the
treatment of solid malignancies, include an antimetabolite with a DNA-damaging
agent, such as gemcitabine with cisplatin and 5FU with the cisplatin analog
oxaliplatin. The combination of 5FU and the topoisomerase inhibitor irinotecan is
based on decreased repair of irinotecan-induced DNA damage. These combinations
may increase induction of apoptosis. The latter combinations have dramatically
changed the treatment of incurable cancers, such as lung and colon cancer, and
have demonstrated that rationally designed drug combinations offer new
possibilities to treat solid malignancies.
PMID- 11008003
TI - Delivery systems for antisense oligonucleotides.
AB - In vitro, the efficacy of the antisense approach is strongly increased by systems
delivering oligodeoxyribonucleotides (ODNs) to cells. Up to now, most of the
developed vectors favor ODN entrance by a mechanism based on endocytosis. Such is
the case for particulate systems, including liposomes (cationic or non-cationic),
cationic polyelectrolytes, and delivery systems targeted to specific receptors.
Under these conditions, endosomal compartments may represent a dead end for ODNs.
Current research attempts to develop conditions for escaping from these
compartments. A new class of vectors acts by passive permeabilization of the
plasma membrane. It includes peptides, streptolysin O, and cationic derivatives
of polyene antibiotics. In vivo, the interest of a delivery system, up to now,
has appeared limited. Development of vectors insensitive to the presence of serum
seems to be a prerequisite for future improvements.
PMID- 11008004
TI - Towards an understanding of the functional significance of N-terminal domain
divergence in human AMP deaminase isoforms.
AB - Human AMP deaminase (AMPD; EC 3.5.4.6) isoforms are encoded by a multigene family
and have conserved C-terminal domains that contain catalytic residues and an ATP
binding site. N-terminal domains diverge dramatically, yet are conserved when
compared across mammalian species. Cross-species conservation of entire gene
specific polypeptides (e.g., rat versus human AMPD1) suggests that divergent N
terminal domains may play a role in isoform-specific properties of the enzyme. It
now has become evident that the majority of published data used to characterize
purified AMPD isoforms were likely derived from preparations lacking significant
portions of their N-terminal domains (up to nearly 100 residues). Accumulating
evidence indicates that divergent N-terminal sequences do influence catalytic
behavior, protein-protein interactions, and intracellular distributions of this
enzyme.
PMID- 11008005
TI - Five year survival and later outcome of patients with X-ray occult lung cancer
detected by sputum cytology.
AB - BACKGROUND: A cohort of 51 consecutive patients with roentgenographically occult
lung cancer, identified by sputum cytology and confirmed by bronchoscopy was
reported previously. METHODS: All patients have now been followed beyond 5 years
and the causes of death ascertained. RESULTS: The actual 5-year survival of 27
patients who were resected for cure was 74% including death for all causes. The 5
year survival of all patients who received either surgery or radiation in an
attempt to cure was 54.3%. Twelve secondary cancers were found by sputum
cytology; eight of these patients have died. CONCLUSIONS: Sputum cytology can be
useful in the identification of early stage lung cancer in patients at high-risk
where the chances of cure are favorable.
PMID- 11008006
TI - Characteristics of lung cancer in Korea, 1997.
AB - The high proportion of smokers and the incidence of advanced, unresectable lung
cancer in Korea were examined to aid the development of a national anti-smoking
program and the early detection of lung cancer. Koreans are a single racial group
with a high smoking rate among men and a contrastingly low smoking rate among
women. This report documents a retrospective investigation conducted by The
Korean Academy of Tuberculosis and Respiratory Disease into the characteristics
of all lung cancers diagnosed between 1 January 1997 and 31 December 1997 in
Korea. Among the 3794 patients included in this study, 76.8% were smokers and, in
particular, 89.8% of the males were smokers. Squamous cell carcinoma was the most
frequent type of lung cancer encountered (44.7%), followed by adenocarcinoma
(27.9%). The smoking rate in the case of adenocarcinoma was significantly lower
than that found in both squamous cell carcinoma and small cell cancer. The most
common symptom was a cough. Only 7.2% of patients were asymptomatic.
Bronchoscopic biopsy has a primary role in the diagnosis of squamous cell
carcinoma and small cell cancer, but percutaneous needle biopsy has a more
important role in the case of adenocarcinoma. Two-thirds of the nonsmall cell
lung cancer patients were detected in the unresectable advanced stages (IIIB and
IV). In contrast to other countries, squamous cell carcinoma is still the most
frequent type of lung cancer in Korea. The high proportion of smokers and the
incidence of advanced, unresectable lung cancer at diagnosis have urged
development of a national anti-smoking program to promote the cessation of
smoking and the early detection of lung cancer.
PMID- 11008007
TI - A systematic review of the role of etoposide and cisplatin in the chemotherapy of
small cell lung cancer with methodology assessment and meta-analysis.
AB - PURPOSE: Cisplatin (CDDP) and etoposide (VP16) are considered major standard
cytotoxic drugs for small cell lung cancer (SCLC). The present systematic review
had as its objective the evaluation of their role, as components of chemotherapy
regimens, on survival. METHODS: Published randomised clinical trials (from 1980
to 1998) were selected comparing, in SCLC patients, chemotherapy regimens, given
as first-line therapy. One arm (the experimental arm) had to include CDDP and/or
VP16, while another had to omit the same drug(s). Trials quality was assessed by
two published scores (Chalmers and European Lung Cancer Working Party (ELCWP)).
For each individual trial, the hazard ratio (HR) of the survival distributions
was estimated on the basis of reported statistics or, if not available, by
extracting, from the survival graphical representations, the data required to
construct the difference between expected and observed numbers of events as
calculated in the log-rank statistic. A combined hazard ratio was obtained by the
Peto method (a value < 1 meaning a benefit for CDDP and/or VP16). RESULTS: Thirty
six trials eligible for our systematic review were identified, classified into
four groups (I-IV): group I, 1 trial testing a CDDP-based regimen (without VP16)
against another arm not including either CDDP or VP16; group II, 17 trials
testing a VP16-based regimen (without CDDP) against a regimen without VP16 and
CDDP; group III, nine trials comparing a regimen including CDDP and VP16 with a
regimen using neither drug; and, finally, group IV, nine trials comparing a
regimen based on both drugs with a regimen based on VP16 only. Overall, Chalmers
and ELCWP scores correlated well (r(S) = 0.76, P < 0. 001) and had respective
median scores of 50.3 and 63.7%. The number of eligible patients did not have a
significant impact on the scores as well as the trials group, the trial
positivity (a positive trial defined as showing itself a statistically
significant survival benefit for the experimental regimen), overall or in
categories, and the year of publication. Combined hazard ratios with 95%
confidence intervals were: 0.70 (0.41-1.21) for group I, 0.72 (0.67-0.78) for II,
0.57 (0.51-0.64) for III, and 0.74 (0.66-0.83) for IV, showing a survival benefit
in favour of regimens including etoposide alone or in combination with cisplatin,
justifying with high significance levels the use of each of these drugs. Overall
survival benefits could also be shown for regimens including CDDP (HR = 0.61;
confidence interval (CI), 0.57-0.66), as well as for those including VP16 (HR =
0. 65; CI, 0.61-0.69). Robustness of these results has to be confirmed with
appropriate randomised trials.
PMID- 11008008
TI - Serum biomarkers of non-neuron-endocrine origin in small-cell lung cancer: a 16
year study on carcinoembryonic antigen, tissue polypeptide antigen and lactate
dehydrogenase.
AB - BACKGROUND: Biomarkers of non-neuron-endocrine origin are measured only
occasionally in the sera of patients with small-cell lung cancer (SCLC). An
exception to this rule is carcinoembryonic antigen (CEA), for which, however,
there is no consistent evidence. Based on such a premise, we decided to review
the Cuneo Lung Cancer Study Group 16-year-experience with non-neuron-endocrine
markers in SCLC. METHODS: a total of 619 CEA, 621 tissue polypeptide antigen
(TPA), and 616 lactate dehydrogenase (LDH) serum assays were obtained from 160
consecutive SCLC at diagnosis, during, and after treatment. Demographic,
clinical, laboratory, and tumoral correlates were also available for another 25
pretreatment and 14 posttreatment variables. RESULTS: bivariate correlation
analyses showed that LDH and TPA were significantly related to each other, and
both of them were also correlated with disease extent, and treatment response.
LDH correlation indexes were higher than that of TPA, especially those regarding
the parameters of disease extent. CEA was correlated only with the category of
treatment response. Receiver-operating characteristic (ROC) analysis confirmed
the correlation between stage disease at diagnosis and both LDH (P = 0.000) and
TPA (P = 0.002), while the treatment failure was better recognized by TPA (P =
0.000). In univariate analysis, both LDH and TPA were correlated with survival (P
= 0.000 and 0.092, respectively); however, only LDH remained significant in
multivariate analysis (P = 0.012). CONCLUSIONS: the evidence from this study does
not suggest a routine CEA test in SCLC. LDH remains particularly useful and it
should be kept in use. Finally, data on TPA is insufficient to advocate its
systematic use in this type of malignancy.
PMID- 11008009
TI - LDH or NSE or LDH and NSE as pretreatment prognostic factors in small cell lung
cancer? A commentary.
PMID- 11008010
TI - Mechanisms of the release of CYFRA21-1 in human lung cancer cell lines.
AB - The CYFRA 21-1 assay which detects cytokeratin 19 (CK19) fragment is widely used
as a tumor marker for lung cancer. However, the reason why some lung cancer cell
lines release CK19 fragment in culture supernatants and others do not, remains
unclear. It was hypothesized that the release of CK19 fragment may be elucidated
by the expression of mRNA for CK19. In order to prove this, the mRNA for CK19 was
quantitatively evaluated by the competitive reverse transcriptase-polymerase
chain reaction (competitive RT-PCR). The level of CYFRA 21-1 in the culture
supernatant was measured by an immunoradiometric assay. CK19 protein synthesis
was evaluated by a Western blotting and immunohistochemistry. Fourteen lung
cancer cell lines were evaluated, and the amount of mRNA correlated well with the
level of CYFRA 21-1 in culture supernatants. Analysis of genomic DNA for CK19
demonstrated that three cell lines which could not produce CYFRA 21-1,
conjectured that some abnormalities in exon 1 or the 5'-region upstream from exon
1. In conclusion, it was demonstrated that the release of CK19 fragment was
closely related to the expression of mRNA for CK19, and the possibility that
genomic change of CK19 DNA down-regulated the expression of mRNA for CK19 was
suggested.
PMID- 11008011
TI - The thin red line: angiogenesis in normal and malignant hematopoiesis.
AB - This review describes the current knowledge about cell subsets involved in
vasculogenesis (i.e., differentiation of endothelial cells from mesodermal
precursors) and angiogenesis (i.e., blood vessel generation from pre-existing
vessels), together with recent findings about angiogenesis and antiangiogenic
therapies in hematopoietic malignancies such as leukemia, lymphoma, myeloma, and
myelodysplastic syndromes.
PMID- 11008012
TI - Granulocyte-macrophage colony-stimulating factor is not responsible for residual
thrombopoiesis in mpl null mice.
AB - OBJECTIVE: To examine the role of granulocyte-macrophage colony-stimulating
factor (GM-CSF) in thrombopoiesis. MATERIALS AND METHODS: Thrombopoietin
unresponsi ve mice (mpl null mice), which have a profound reduction in platelets
and mature megakaryocytes, were interbred with mice that do not respond to GM-CSF
or interleukin 5 (betac null mice), and hematopoiesis was examined. In initial
experiments on a mixed genetic background, double mutant mice (betac/mpl null
mice) showed an unexpected amelioration of the thrombocytopenia seen in mpl null
mice. Platelet counts were elevated approximately twofold in betac/mpl null mice
compared with mpl null mice (mpl null 73+/-31; betac/mpl null 164+/-70; n = 10 to
29 mice per genotype, p<0.00001). This was associated with lessening of the
deficit of megakaryocytes, progenitor cells, and colony-forming units spleen seen
in mpl null mice. This amelioration of the mpl null phenotype in betac/mpl null
mice on a mixed genetic background was highly statistically significant. To
determine whether this amelioration of phenotype was solely the consequence of
loss of betac signaling, progeny of a second intercross on a C57BL/6 background
(B6betac/mpl null mice) were examined. When the resulting B6betac/mpl null mice
were analyzed and compared with B6mpl null littermates, the increase in platelet
count, hematopoietic progenitor cell number, and colony-forming units spleen
number was no longer observed. CONCLUSION: There was no additional effect seen as
a result of loss of betac signaling. GM-CSF did not play a significant role in
thrombopoiesis, even in combination with the absence of thrombopoietin signaling.
These results highlight problems that can be encountered when studying introduced
mutations in mice. They exemplify the importance of eliminating the influence of
modifying genes when attributing biologic differences to specific introduced
genetic alterations.
PMID- 11008013
TI - Tumor necrosis factor-alpha-induced proliferation requires synthesis of
granulocyte-macrophage colony-stimulating factor.
AB - OBJECTIVE: Tumor necrosis factor- alpha (TNF-alpha) induces a variety of cellular
responses, some of them being at least seemingly contradictory. Thus, we set out
to find differences in the modes of proliferative and apoptotic responses to TNF-
alpha. MATERIALS AND METHODS: We screened a panel of acute myeloid leukemia
derived cell lines for TNF- alpha-responsiveness. In two lines (OCI-AML-1, OCI
AML-11), TNF- alpha acted as an apoptotic agent; in others (HU-3, M-07e, TF-1),
it had the opposite effect, preventing apoptosis and inducing proliferation.
Direct and indirect signaling mechanisms, including NF-kappaB activation and
cytokine synthesis, were analyzed. RESULTS: All cell lines tested expressed TNF-
alpha receptors I and II and responded to TNF- alpha by upregulation of
intercellular adhesion molecule-1. In contrast to granulocyte-macrophage colony
stimulating factor (GM-CSF), TNF- alpha did not activate the MAP kinase and p70S6
kinase pathways. Nevertheless, inhibitors of these pathways clearly reduced the
TNF-alpha-induced cell growth, indicating that TNF- alpha-proliferative cells
produced a growth factor that induced proliferation upon stimulation of the above
pathways. Anti-GM-CSF antibodies inhibited the TNF-alpha-induced growth,
suggesting the presence of an autocrine loop for cell proliferation mediated by
GM-CSF. Supporting this notion, TNF-alpha-induced upregulation of GM-CSF mRNA
levels and protein secretion in the TNF-alpha-proliferative, but not in the TNF
alpha-apoptotic cell lines. CONCLUSION: These data identify GM-CSF synthesis as
an early and essential step in TNF- alpha-induced proliferation. We show for the
first time that TNF-alpha-treated cell lines producing no or only minimal amounts
of GM-CSF demonstrate an apoptotic phenotype, while cell lines with high GM-CSF
expression rates can escape from growth arrest or even apoptosis. In this
context, we discuss arguments pointing at NF-kappaB as regulator of GM-CSF
synthesis and thus indirectly as regulator for the escape of TNF-alpha-induced
apoptosis.
PMID- 11008014
TI - Dynamic model of ex vivo granulocytic kinetics to examine the effects of oxygen
tension, pH, and interleukin-3.
AB - OBJECTIVE: Evaluating kinetics in hematopoietic cultures is complicated by the
distribution of cells over various stages of differentiation and by the presence
of cells from different lineages. Thus, an observed response is an integral
response from distributed cell populations. Growth factors and other parameters
can greatly affect the lineage and maturation stage of the culture outcome. To
resolve the kinetics and more clearly define the differential effects of O(2)
tension (pO(2)), pH, and interleukin-3 (IL-3) on granulopoiesis, a mathematical
model-based approach was undertaken. MATERIALS AND METHODS: Granulocytic
differentiation is described within a continuous, deterministic framework in
which cells develop from primitive granulocytic progenitors to mature
neutrophils. The model predicts two distributed populations-quiescent and cycling
cells-by incorporating rates of growth, death, differentiation, and transition
between quiescence and active cycling. The response of these four model processes
to changes in the culture environment was examined. RESULTS: Model simulations of
experimental data revealed the following: 1) pO(2) effects are exerted only on
the growth rate but not maturation times. 2) pH effects between pH 7.25 and 7.4
on growth and differentiation are coupled; however, with increasing pH values,
especially at pH 7. 6, the death rate for cells in the early stages of
differentiation becomes increasingly significant. 3) The absence of IL-3
increases the death rate for primitive cells only minimally but markedly enhances
the rate of differentiation through the myeloblast window in the differentiation
pathway. The combined effects of these environmental factors can be predicted
based on changes in the model parameters derived from the individual effects.
CONCLUSIONS: Experimental data combined with mathematical modeling can elucidate
the mechanisms underlying the regulation of granulopoiesis by pO(2), pH, and IL
3. The model also can be readily adapted to evaluate the effects of other culture
conditions. The increased understanding of experimental results gained with this
approach can be used to modify culture conditions to optimize ex vivo production
of neutrophil precursors.
PMID- 11008015
TI - Enhanced proteolysis of pre-mRNA splicing factors in myeloid cells.
AB - OBJECTIVE: Molecular identification and characterization of the bone marrow
nuclear protein detected by the B92 monoclonal antibody. MATERIALS AND METHODS:
The protein was purified to homogeneity from acute myeloid leukemia cells and was
subjected to peptide digestion and amino acid sequencing. Identified sequences
were used to screen a bone marrow cDNA library in search of matching transcripts.
The protein was further studied in different cells and tissues by examination of
protease inhibitors and harsh lytic conditions and during apoptosis in HL-60
cells. RESULTS: We found that the apparent bone marrow specific protein is a 47
kD proteolytic cleavage product of PSF, an essential pre-mRNA splicing factor.
PSF is completely cleaved to p47 during lysis of immature myeloid cells due to
potent proteolytic activity found in these cells but is rare in other cells and
tissues. Furthermore, p47 is abundant in intact normal and tumor myeloid cells
while in other cell types it is undetectable. The cleavage of PSF is accompanied
by digestion of the PTB splicing regulator but not other proteins tested. In
contrast, during apoptosis PTB is degraded while PSF remains intact. CONCLUSIONS:
The bone marrow 47 kD protein is a fragment constituting the N-terminal, protease
resistant half of the splicing factor PSF. Proteolytic degradation of PSF
specifically occurs in intact myeloid cells and this process is enhanced upon
myeloid cell lysis.
PMID- 11008016
TI - Quantitation of minimal residual disease in multiple myeloma using an allele
specific real-time PCR assay.
AB - OBJECTIVE: To develop a real-time PCR method, based on the 5'nuclease TaqMan
technology, for quantitation of clonal cells in multiple myeloma (MM). MATERIALS
AND METHODS: The real-time quantitative PCR method incorporates both an allele
specific oligonucleotides (ASO) primer and an ASO dual-labeled fluorogenic probe
(ASO TaqMan probe). The ASO primer and probe corresponded to the complementary
determining region 3 (CDR3) of the rearranged immunoglobulin heavy chain gene
(IgH). With the use of a sequence detector, PCR product accumulation was measured
through the ASO TaqMan probe. The real-time PCR method was compared with flow
cytometric quantitation of myeloma plasma cells. RESULTS: The application of the
real-time quantitative ASO IgH PCR method is illustrated by a sequential analysis
of minimal residual disease (MRD) in bone marrow (BM) samples from myeloma
patients undergoing peripheral blood stem cell (PBSC) transplantation. The real
time PCR method was able to quantitate residual malignant cells in BM samples
from patients who were considered to be in complete remission. Further, it was
illustrated that a potential problem in determining tumor cell content in myeloma
BM samples is the heterogeneous infiltration of the marrow. CONCLUSION: The
application of the real-time PCR method provides a sensitive, highly specific,
and reproducible quantitation of myeloma cells.
PMID- 11008017
TI - Transplantation and growth characteristics of human fetal lymph node in
immunodeficient mice.
AB - OBJECTIVE: The lymph node is an integral component of the immune system and the
major site of antigen-dependent lymphocyte proliferation and differentiation.
Development of animal models possessing functional primary human lymph nodes will
have a significant impact on research in lymphopoiesis and immune response. To
date, successful transplantation of primary human lymph nodes in rodents has not
yet been reported. This work was undertaken to develop a reliable methodology to
engraft primary human fetal lymph nodes in immunodeficient mice. MATERIALS AND
METHODS: Three different sets of parameters, including three different
transplantation sites in the mice, two different strains of immunodeficient mice,
and two different preconditioning regimens, were evaluated. The growth
characteristics of the implanted primary human fetal lymph nodes were examined 3
months after transplantation by histologic, immunocytochemical, and flow
cytometric methods. RESULTS: Transplantation of primary human fetal lymph nodes
into subcutaneous pouches in the ears in severe combined immunodeficiency (SCID)
mice preconditioned with etoposide reproducibly give rise to >80% engraftment.
The engrafted primary human fetal lymph nodes undergo massive growth (>200-fold)
and retain the same histology and cellular composition as fresh human fetal lymph
nodes from the same donors. CONCLUSIONS: We report, for the first time, the
development of a reliable methodology to successfully engraft human fetal lymph
node in SCID mice. The engrafted human lymph nodes are visible and accessible to
experimental manipulations. This SCID-hu mouse model with human lymph node should
provide a physiologically relevant system to investigate lymphopoiesis,
immunologic response, and virus-mediated immunosuppression.
PMID- 11008018
TI - Differences in megakaryocyte expansion potential between CD34(+) stem cells
derived from cord blood, peripheral blood, and bone marrow from adults and
children.
AB - OBJECTIVE: Reinfusion of ex vivo expanded autologous megakaryocytes together with
stem cell transplantation may be useful to prevent or reduce the period of
chemotherapy-induced thrombocytopenia. We compared the megakaryocyte expansion
potential of CD34(+) stem cells derived from different sources: cord blood (CB),
peripheral blood (PB), bone marrow from adults (ABM), and bone marrow from
children (ChBM). Three different growth factor combinations were tested to
identify the best combination for each of the sources. MATERIALS AND METHODS:
CD34(+) cells were isolated from CB, PB, ABM, or ChBM and cultured in an in vitro
liquid culture system in the presence of thrombopoietin (Tpo), Tpo + interleukin
(IL-1), or Tpo + IL-3. After 8 days, proliferation was determined and the
cultured cells were identified with lineage-specific surface markers by flow
cytometry. RESULTS: Cultures with ChBM-derived CD34(+) cells showed the lowest
level of expansion of megakaryocytes and gave rise to more profound formation of
myeloid and monocytic cells. In cultures with BM- or PB-derived cells, presence
of IL-3 reduced the number of immature megakaryocytes (CD34(+)CD41(+) cells).
However, in CB cultures, the number of CD34(+)CD41(+) cells was highest in
cultures with Tpo + IL-3. Overall, cultures with CB CD34(+) cells yielded the
highest number of megakaryocytes, but these cells showed reduced ploidization and
lower level of CD41 expression, suggesting less maturation. CONCLUSIONS: Each of
the different CD34(+) cell sources responded differently to cytokine stimulation.
For PB and ABM, the cytokine combination Tpo + IL-1 is most suitable to obtain
high numbers of both immature and mature megakaryocytes for transfusion purposes.
For CB, Tpo + IL-3 is better.
PMID- 11008019
TI - Effects of the protein tyrosine phosphatase CD45 on FcgammaRIIa signaling and
neutrophil function.
AB - OBJECTIVE: Neutrophil receptors for the Fc portion of IgG (FcgammaR) trigger
immune responses following cross-linking by IgG-coated foreign particles or
immune complexes. Membrane-associated CD45, a protein tyrosine phosphatase termed
leukocyte common antigen, has been shown to be essential for antigen receptor
kinase mediated signaling in lymphocytes, and we hypothesized that CD45 may play
a similar role in FcgammaR-mediated signaling and immune function in human
neutrophils. METHODS: The experimental approach was that of cell surface molecule
ligation via cross-linking with specific antibodies. Antibody dependent cellular
cytotoxicity (ADCC) was assessed using a single-cell plaque assay and IL-6
production measured using ELISA. Tyrosine phosphorylation levels were assessed
with anti-phospho-tyrosine blots and F-actin polymerization by flow cytometry and
confocal microscopy. RESULTS: Neutrophils pretreated with anti-CD45 had a reduced
ability to perform ADCC compared to untreated neutrophils. FcgammaRIIa cross
linking resulted in significantly increased concentrations of secreted IL-6
compared to untreated neutrophils, and IL-6 production was further enhanced by
cocross-linking CD45 with FcgammaRIIa. Cross-linking CD45 alone also induced IL-6
production. FcgammaRIIa cross-linking resulted in increased protein tyrosine
phosphorylation and F-actin polymerization in neutrophils. Cocross-linking CD45
with FcgammaRIIa resulted in abrogation of FcgammaRIIa mediated tyrosine
phosphorylation and F-actin polymerization. CONCLUSIONS: These data provide
evidence that CD45 can regulate or enhance the stimulation and function of human
neutrophils mediated through FcgammaR(s). In addition, CD45 ligation may play an
essential role in cytokine induction pathways that lead to inflammatory reactions
in vivo.
PMID- 11008020
TI - Kinetics of engraftment of CD34(-) and CD34(+) cells from mobilized blood differs
from that of CD34(-) and CD34(+) cells from bone marrow.
AB - OBJECTIVE: Mobilized peripheral blood (PB) progenitors are increasingly used in
autologous and allogeneic transplantation. However, the short- and long-term
engraftment potential of mobilized PB or bone marrow (BM) has not been directly
compared. Although several studies showed that BM-derived Lin(-)CD34(-) cells
contain hemopoietic progenitors, no studies have addressed whether Lin(-)CD34(-)
cells from mobilized PB contain hemopoietic progenitors. Here, we compared the
short- and long-term engraftment potential of CD34(+) cells and Lin(-)CD34(-)
cells in BM and PB of normal donors who received 5 days of granulocyte colony
stimulating factor (G-CSF). MATERIALS AND METHODS: 35 x 10(3) CD34(+) or Lin(
)CD34(-) cells from G-CSF mobilized BM and PB of normal donors were transplanted
in 60-day-old fetal sheep. Animals were evaluated 2 and 6 months after
transplantation for human hemopoietic cells. In addition, cells recovered after 2
months from fetal sheep were serially passaged to secondary and tertiary
recipients to assess long-term engrafting cells. RESULTS: Mobilized PB CD34(+)
cells supported earlier development of human hemopoiesis than BM CD34(+) cells.
When serially transferred to secondary and tertiary recipients, earlier
exhaustion of human hematopoiesis was seen for PB than BM CD34(+) cells. A
similar degree of chimerism was seen for Lin(-)CD34(-) cells from PB or BM in
primary recipients. We again observed earlier exhaustion of human hemopoiesis
with serial transplantation of PB than BM Lin(-)CD34(-) cells. CONCLUSIONS:
Differences exist in the short- and long-term repopulating ability of cells in PB
and BM from G-CSF mobilized normal donors, and this is independent of the
phenotype. Studies are ongoing to examine if this reflects intrinsic differences
in the repopulating potential between progenitors from PB and BM, or a lower
frequency of long-term repopulating cells in PB than BM CD34(+) and Lin(-)CD34(-)
cells, that may not be apparent if larger numbers of cells are transplanted.
PMID- 11008021
TI - High frequency of long-term culture-initiating cells retain in vivo repopulation
and self-renewal capacity.
AB - OBJECTIVE: We wished to test if the long-term culture initiating cell (LTC-IC)
assay measures primitive hematopoietic stem cells. An LTC-IC is defined by its
ability to repopulate a stromal layer by forming colonies of myeloid cells. A
negative well should never have received a stem cell, whereas a positive well
should have been initiated by a stem cell. If these colonies were derived from
stem cells, then a subset of the positive wells should retain stem cell activity.
MATERIALS AND METHODS: Limiting dilution cultures were initiated on the stromal
cell line S17. Individual clonal cultures from LTC-IC assays were assessed for
repopulation capacity in W(14)W(41) mice. RESULTS: In long-term repopulation
experiments, little activity was found in the negative wells, whereas 50% of the
positive wells contained repopulating stem cells. The diverse in vivo
repopulation patterns of the clonally derived stem cells suggest that this assay
detects the full spectrum of stem cell types. Secondary transfers show that the
clonally derived stem cells have self-renewal capacity. Experiments with mixtures
of genetically distinguished cells showed that most (>90%) of the cultures were
clonal. CONCLUSIONS: Our data present the first formal link between LTC-IC and
repopulating stem cells. Moreover, the culture system presents a new way of
generating a high frequency of clonally repopulating stem cells.
PMID- 11008022
TI - Multi-lineage expansion potential of primitive hematopoietic progenitors:
superiority of umbilical cord blood compared to mobilized peripheral blood.
AB - OBJECTIVE: The majority of studies assessing ex-vivo expansion of primitive
hematopoietic cells only address production of myeloid progeny whereas it may be
more appropriate to maintain or expand progenitors that retain capacity for
multilineage differentiation. In this study, we assessed the capacity of the
murine fetal liver cell line AFT024 to expand primitive myeloid progenitors (LTC
IC) and lymphoid progenitors (NK-IC) from umbilical cord blood (CB) and mobilized
peripheral blood (PB) CD34(+)lin(-)38(-) cells. METHODS: Sorted cells were
established in expansion cultures in direct contact with the feeder or in a
transwell above the feeder (noncontact culture) and various combinations of Flt
3L (FL), stem cell factor, interleukin 7, thrombopoietin (Tpo), and macrophage
inflammatory protein-1alpha added. Frequency of LTC-IC and NK-IC was assessed at
day 0 and following 2 and 5 weeks expansion culture. RESULTS: CB contained
significantly more LTC-IC and NK-IC at day 0 and showed an enhanced capacity for
expansion compared to PB. The combination of FL and Tpo showed maximal expansion
of CB LTC-IC and NK-IC at 5 weeks in both contact and noncontact conditions. In
contrast, expansion of PB LTC-IC and NK-IC was maximal at 2 weeks and required
multiple cytokines. CONCLUSIONS: These results demonstrate that AFT024 can expand
primitive hematopoietic progenitors from CB and PB and expanded cells retain the
capacity for myeloid and lymphoid differentiation. These findings emphasize the
importance of assessing multi-lineage differentiation capacity following ex-vivo
expansion. Elucidation of specific factors necessary for ex-vivo expansion will
contribute to the development of a clinically applicable system.
PMID- 11008023
TI - Second allogeneic stem cell transplantation using nonmyeloablative conditioning
for patients who relapsed or developed secondary malignancies following
autologous transplantation.
AB - OBJECTIVE: Second allogeneic stem cell transplants for hematological malignancies
are associated with a high incidence of transplant-related mortality due to the
cumulative incidence of toxicity of the high-dose chemoradiotherapy traditionally
used as an essential component of the conditioning. We have demonstrated
previously that nonmyeloablative conditioning for primary allogeneic transplants
from both sibling and unrelated donors results in minimal transplant-related
toxicity and excellent stem cell engraftment. This study explores the possibility
of using nonmyeloablative conditioning to minimize transplant-related toxicity in
patients who have undergone second allogeneic transplants. PATIENTS AND METHODS:
Twelve high-risk, heavily treated patients-five with acute myelogenous leukemia
(AML); five with non-Hodgkin's lymphoma (NHL); one with Burkitt's lymphoma, and
one with acute lymphoblastic leukemia (ALL)-underwent second allogeneic
nonmyeloablative stem cell transplantation (NST) from human leukocyte antigen
(HLA)-matched donors, 29 (median) (range 3-57) months following their first
transplantation procedure. The conditioning consisted of fludarabine 30 mg/m(2)
daily for 6 days, busulfan 4 mg/kg daily for 2 days, and anti-T-lymphocyte
globulin 10 mg/kg daily for 4 days. Anti-graft-vs-host disease (anti-GVHD)
prophylaxis consisted of cyclosporine A alone, 3 mg/kg. RESULTS: Engraftment was
observed in all recipients, with complete and stable chimerism. None of the
patients developed veno-occlusive disease of the liver or multi-organ failure.
Five very high-risk patients with NHL (n = 3), Burkitt's lymphoma (n = 1), and
AML (n = 1) relapsed 2 to 6 months post-transplant, and four of them died. Six
patients appear to be disease-free after median follow-up of 23 months. One
additional patient died from grade IV hemorrhagic cystitis. Actuarial survival
and disease-free survival at 34 months are 56% and 50% respectively, with 95%
confidence interval (25-78%). CONCLUSION: These results suggest that
nonmyeloablative conditioning significantly reduces transplant-related toxicity,
thus making a second transplant feasible.
PMID- 11008024
TI - Refractive surgery for keratoconus: a new approach.
PMID- 11008025
TI - Consultation section: refractive surgical problem.
PMID- 11008026
TI - Refractive surgical problem
PMID- 11008027
TI - Refractive surgical problem
PMID- 11008028
TI - Refractive surgical problem
PMID- 11008029
TI - Refractive surgical problem
PMID- 11008030
TI - Refractive surgical problem
PMID- 11008031
TI - Refractive surgical problem
PMID- 11008032
TI - Refractive surgical problem
PMID- 11008033
TI - Refractive surgical problem
PMID- 11008034
TI - Refractive surgical problem
PMID- 11008035
TI - Refractive surgical problem
PMID- 11008036
TI - Cataract in enucleated goat eyes: training model for phacoemulsification.
AB - We developed an inexpensive, reproducible technique of inducing cataract in
enucleated animal eyes for phacoemulsification training. Injection of 0.3 to 0.5
mL of formalin 20% in the central and paracentral portion of the crystalline lens
in a goat's eye induced cataract in about 5 to 10 minutes. Varying the interval
would enable novice surgeons to practice different techniques of
phacoemulsification based on cataract hardness.
PMID- 11008037
TI - Correcting keratoconus with intracorneal rings.
AB - PURPOSE: To evaluate the potential of intrastromal corneal ring technology
(Intacs, KeraVision) to correct keratoconus without central corneal scarring.
SETTING: Department of Ophthalmology, Brest University Hospital, Brest, France.
METHODS: In this prospective, noncomparative, interventional case series, Intacs
segments were implanted in 10 keratoconic eyes with clear central corneas and
contact lens intolerance after corneal pachymetry was checked. Segment
thicknesses varied based on corneal topography analysis. RESULTS: No
intraoperative complications occurred. The mean follow-up was 10.6 months.
Postoperative results revealed a reduction in astigmatism and spherical
correction and an increase in topographical regularity and increased uncorrected
visual acuity. CONCLUSION: Intacs technology can reduce the corneal steepening
and astigmatism associated with keratoconus.
PMID- 11008038
TI - Theoretical analysis of ablation depths and profiles in laser in situ
keratomileusis for compound hyperopic and mixed astigmatism.
AB - PURPOSE: To compare the theoretical ablation depths and profiles of 4 treatment
strategies for compound hyperopic and mixed astigmatism. SETTING: Theoretical
analysis. METHODS: Corneal contour drawings of theoretical corneal ablation
profiles during laser in situ keratomileusis (LASIK) and photoastigmatic
refractive keratectomy were made. The depths of tissue ablation in 4 treatment
strategies for compound hyperopic astigmatism (Groups 1 to 4) and for mixed
astigmatism (Groups 5 to 8) were compared: (1) combined hyperopic spherical and
myopic cylindrical treatments (Groups 1 and 5); (2) combined spherical and
hyperopic cylindrical treatments (Groups 2 and 6); (3) combined cylindrical
treatments (Groups 3 and 7); (4) combined cross-cylinder and spherical equivalent
treatments (Groups 4 and 8). RESULTS: In compound hyperopic astigmatism, the 4
approaches resulted in identical final curvatures, but the ablation depths were
greatest in Group 1 (combined hyperopic spherical and myopic cylindrical
treatments). The smallest amount of ablation occurred in Group 2 (combined
hyperopic spherical and hyperopic cylindrical treatments) and Group 3 (combined
hyperopic cylindrical treatments), which had similar tissue ablation patterns. In
mixed astigmatism, the greatest ablation depth was in Group 5, followed by Group
8, and Groups 6 and 7. The tissue ablation depths and profiles were similar in
Groups 6 and 7. CONCLUSION: The treatment approaches in Groups 2, 3, 6, and 7
(which avoided the use of minus cylinder) resulted in the smallest degree of
stromal ablation. Patients with compound hyperopic or mixed astigmatism may
benefit from reduced ablation depths by deferring treatment until hyperopic
cylindrical and/or combined cylindrical treatments are available.
PMID- 11008039
TI - Comparison of optical zones in hyperopic laser in situ keratomileusis: 5.9 mm
versus smaller optical zones.
AB - PURPOSE: To compare the results of hyperopic laser in situ keratomileusis (LASIK)
with a 5.9 mm optical zone (OZ) with those with smaller zones (4.4 to 5.5 mm).
SETTING: Instituto de la Vision, Buenos Aires, Argentina. METHODS: The results of
LASIK with a 5.9 mm OZ (147 cases) were compared with those in a previously
reported group treated with OZs of 4.4 to 5.5 mm (679 cases). In the 5.9 mm
group, 31.3% (46 eyes) had low hyperopia, 46.9% (69 eyes) had moderate hyperopia,
and 21.8% (32 eyes) had high hyperopia. In the smaller OZ group, follow-up was 1
month in 79.4% (539 eyes), 3 months in 75.5% (501 eyes), 6 months in 68.5% (465
eyes), and 1 year in 38.3% (260 eyes). The hyperopic population studied was
divided into 3 subgroups based on the preoperative spherical equivalents of the
manifest refraction: subgroup A, low hyperopia: < or = +2.0 diopters (D);
subgroup B, moderate hyperopia: +2.0 to +3.0 D; and subgroup C, high hyperopia: >
+3.0 D. The following parameters were measured postoperatively: uncorrected
visual acuity (UCVA), best corrected visual acuity (BCVA), refraction (evolution
and distribution), and visual acuity lines gained and lost. RESULTS: The
preoperative mean spherical equivalents in the 5.9 mm OZ group were +1.47 +/-
0.41 (SD) (subgroup A); +2.98 +/- 0.41 (subgroup B); and +5.13 +/- 0.61 (subgroup
C). In the smaller OZ group, they were +1.31 +/- 0.74, +2.56 +/- 0.28, and +5.28
+/- 0. 69, respectively. At 12 months, the distribution of eyes in the 5.9 mm OZ
group with refractions within +/-1.0 D were as follows: subgroup A, 100%;
subgroup B, 100%; and subgroup C, 94.2%. In the smaller OZ group, the
distributions were 100%, 95.3%, and 71.4%. In the 5.9 mm and the smaller OZ
groups, the UCVA was 20/40 or better in 92.0% and 81.8% of eyes, respectively, in
subgroup A; 94.6% and 100%, respectively, in subgroup B; and 76.5% and 77.9%,
respectively, in subgroup C. The percentage of eyes with 0 +/- 1 line of BCVA 12
months after the procedure was also determined in the 5.9 mm OZ group and
compared with the percentages in the smaller OZ group. CONCLUSION: Results of
hyperopic LASIK with a 5.9 mm OZ in eyes with low, moderate, and high hyperopia
are more stable, predictable, and safe than those in eyes with OZs smaller than
5.9 mm.
PMID- 11008040
TI - Accuracy and predictability of intraocular lens power calculation after
photorefractive keratectomy.
AB - PURPOSE: To investigate the accuracy and predictability of intraocular lens (IOL)
power calculation in postoperative photorefractive keratectomy (PRK) eyes.
SETTING: Gimbel Eye Centre, Calgary, Alberta, Canada. METHODS: The results in 5
cataract surgery eyes that had had PRK were analyzed retrospectively. Target
refractions based on actual and refraction-derived keratometric values were
compared with postoperative achieved refractions. The target refractions
calculated using 5 IOL formulas and 2 A-constants were also compared with the
achieved refractions. RESULTS: In postoperative PRK eyes, the power calculation
was more accurate and predictable when the smaller of either the actual or
refraction-derived keratometric value was used to calculate the IOL power. The
difference between target and achieved refractions appeared smaller when the
Binkhorst formula was used. No significant hyperopic shift was observed after
cataract surgery. CONCLUSION: The smaller of the actual or the refraction-derived
keratometric value is recommended for calculating IOL power in post-PRK eyes.
PMID- 11008041
TI - Laser in situ keratomileusis to correct residual myopia and astigmatism after
radial keratotomy.
AB - PURPOSE: To evaluate the safety and efficacy of laser in situ keratomileusis
(LASIK) in selected post-radial-keratotomy (RK) eyes with residual myopia and
astigmatism. SETTING: TLC-The Brea Laser Eye Center, Brea, California, USA.
METHODS: Nine eyes of 6 patients who had had RK but had residual myopia and/or
astigmatism had LASIK. All RK eyes had 8 radial incisions, were more than 1 year
post-RK, had no epithelial inclusion cysts or corneal disease, and had had no
subsequent ocular surgery. Follow-up was a minimum of 13 months, at which time
uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), manifest
refraction, cycloplegic refraction, keratometry, central and peripheral
pachymetries, intraocular pressure, and a subjective assessment of visual
function were obtained. RESULTS: At the last follow-up, the mean spherical
equivalent (SE) was -0.156 diopter (D) +/- 0.174 (SD). All eyes treated for
distance vision had a UCVA of 20/25 or better. No patient lost BCVA. No
intraoperative or postoperative complications occurred. Seven eyes had morning
and evening measurements. The mean change in manifest SE from morning to evening
was -0.143 D. Six of the 7 eyes (86%) had 0 to 1 Snellen line change in UCVA from
morning to evening. The subjective questionnaire revealed a high degree of
satisfaction with overall vision, minimal glare, and less fluctuation in daily
vision than before LASIK. CONCLUSION: Laser in situ keratomileusis is safe and
efficacious for reducing residual myopia and astigmatism in properly selected RK
patients.
PMID- 11008042
TI - Outcome of flap subluxation after laser in situ keratomileusis: results of 6
month follow-up.
AB - PURPOSE: To evaluate the long-term outcome in cases with flap subluxation after
laser in situ keratomileusis (LASIK). SETTING: Private clinic in Turkey. METHODS:
Data of all patients who had LASIK were documented and the follow-ups of those
who had flap subluxation evaluated. The number of LASIK cases was 1481 and the
number of flap subluxations, 21. Laser in situ keratomileusis was performed with
the Moria microkeratome and the VISX Twenty/Twenty B excimer laser using a
multizone profile and the sutureless hinged corneal flap technique. RESULTS: The
incidence of flap subluxation was 1.42%. Statistical analysis of uncorrected
visual acuities, best corrected visual acuities, and mean spherical equivalents
in eyes with and without flap subluxation was performed. No significant
differences were found, although the results in eyes with flap subluxation were
worse than those in eyes without flap subluxation. Additional complications were
also higher in eyes with flap subluxation. CONCLUSION: Flap subluxation is a
serious but manageable complication of LASIK. If it is detected early, the visual
prognosis is as good as that in eyes without flap subluxation.
PMID- 11008043
TI - Multicenter study of the Artisan phakic intraocular lens.
AB - PURPOSE: To assess the Artisan intraocular lens to correct myopia in phakic eyes.
SETTING: European multicenter study sponsored by Ophtec BV, Groningen, The
Netherlands. METHODS: In this prospective multicenter clinical study, the Artisan
lens was implanted in 518 eyes between September 1991 and October 1999. The power
of the lenses ranged from -5.0 to -20.0 diopters (D). Follow-up examinations were
performed at 6 months and 1, 2, and 3 years. Follow-up ranged from 6 months (n =
454) to 3 years (n = 249). The preoperative uncorrected visual acuity (UCVA) was
not recorded but was estimated to be worse than 0.1. The preoperative mean best
spectacle-corrected visual acuity (BSCVA) was 0.67 +/- 0.26 (SD). Endothelial
cell counts were done at 6 months and 1, 2, and 3 years in a subgroup of 129
eyes. RESULTS: A UCVA of 20/40 or better was observed in 76.8% of eyes regardless
of the postoperative goal. A BSCVA of 20/40 or better was observed in 93.9% of
eyes and remained stable throughout the follow-up. Of the eyes with extremely
high myopia (>-15.0 D), 63.3% gained 2 or more lines of BSCVA; of those with
moderate myopia (-5.0 to -10.0 D), 23.5% gained 2 or more lines. The mean
endothelial cell density change was 4.8% at 6 months, 2.4% at 1 year, 1.7% at 2
years, and 0.7% at 3 years. The incidence of persistent adverse events at 3 years
was relatively low. Secondary surgical interventions included repositioning of
the lens because of poor initial placement and lens exchange because of
preoperative power calculation errors. Glare and halo effects during night
driving were noted and were related to large pupils in young patients.
CONCLUSION: The Artisan lens is a safe, stable, efficacious, and predictable
method to correct -5.0 to -20.0 D of myopia. This study suggests that the corneal
endothelial cell loss is stabilized to the physiologically normal level after 3
years.
PMID- 11008044
TI - Long-term results of the foldable CeeOn Edge intraocular lens.
AB - PURPOSE: To determine the long-term efficacy and safety of the foldable silicone
CeeOn Edge(R) model 911 intraocular lens (IOL). SETTING: Eye Clinic, Klinikum
Minden, Germany. METHODS: A high-refractive-index silicone lens with a sharp edge
was implanted after phacoemulsification in 42 eyes of 36 patients. Best corrected
visual acuity (BCVA) and occurrence of complications were evaluated during a 3
year follow-up. RESULTS: No significant postoperative complications were seen. At
3 years, 26 eyes of 22 patients were available for examination. The BCVA was 0.5
(20/40) or better in 92% of eyes and 1.0 (20/20) or better in 39%. No posterior
capsule opacification (PCO) was observed, and neodymium:YAG capsulotomy was not
indicated in any patient. CONCLUSIONS: This pilot study indicates that the
performance and safety of the foldable silicone CeeOn Edge lens are excellent.
The results support the theory that a sharp edge on the IOL prevents the
development of PCO.
PMID- 11008045
TI - Posterior capsule opacification 3 years after implantation of an AcrySof and a
MemoryLens in fellow eyes.
AB - PURPOSE: To compare the rates of lens epithelial cell (LEC) migration and
posterior capsule opacification (PCO) 1 and 3 years after sutureless small
incision phacoemulsification and in-the-bag implantation of 2 acrylic polymer
intraocular lenses (IOLs)-the AcrySof and MemoryLens-in fellow eyes of patients.
SETTING: Eye Clinic, Beyoglu Education and Research Hospital, Istanbul, Turkey.
METHODS: Fifty patients with no systemic or ocular problems that would interfere
with postoperative visual acuity were included in this prospective study. Each
patient had in-the-bag implantation of an AcrySof IOL in 1 eye and a MemoryLens
in the fellow eye in a randomized fashion after uneventful phacoemulsification
through a sutureless clear corneal incision. RESULTS: At 1 year (n = 32
patients), there was no significant difference between fellow eyes in
postoperative best corrected visual acuity (BCVA) and contrast sensitivity. In
the MemoryLens group, 10 eyes (31.3%) had PCO and 9 (28.1%), LEC migration. In
the AcrySof group, no eye had PCO and 2 eyes (6.3%) had LEC migration (P <.001).
At 3 years (n = 21 patients), 1 eye (4.7%) in the AcrySof group had PCO and 3
eyes (14.4%) had LEC migration without PCO. In the MemoryLens group, 1 eye (4.7%)
had a clear posterior capsule, 11 eyes (52.4%) had LEC migration, and 9 eyes
(42.9%) had PCO (P <.001). A neodymium:YAG capsulotomy was required in 4 eyes
(19.0%) in the MemoryLens group but no eye in the AcrySof group. At 3 years, BCVA
was lower in the MemoryLens group than in the AcrySof group (P <.05). CONCLUSION:
The 3 year clinical data of fellow eyes indicate that the AcrySof IOL causes less
PCO than the MemoryLens.
PMID- 11008046
TI - Influence of laser posterior capsulotomy on anterior chamber depth, refraction,
and intraocular pressure.
AB - PURPOSE: To evaluate the effect of neodymium:YAG (Nd:YAG) laser posterior
capsulotomy on anterior chamber depth (ACD), intraocular pressure (IOP), and
refraction, including spherical equivalent (SE) and various forms of astigmatism.
SETTING: Taipei Municipal Yang-Ming Hospital, Taipei, Taiwan. METHODS: Fifty
three eyes of 46 patients with posterior capsule opacification were included in
this prospective study. An Nd:YAG laser was used to perform posterior
capsulotomy. Patients' ACD, IOP, and refraction were measured before the
capsulotomy and 30 minutes, 1 week, and 1 and 3 months after. RESULTS: There were
no statistically significant differences in ACD, IOP, or SE (P =.201, P =.465,
and P =.109, respectively). However, there were significant decreases in the
magnitudes of refractive astigmatism and residual astigmatism after laser
treatment (P =.012 and P <.001, respectively). CONCLUSIONS: Although an Nd:YAG
laser posterior capsulotomy did not significantly change ACD, IOP, or SE, it
decreased the magnitudes of refractive astigmatism and residual astigmatism 1
week postoperatively. These stabilized thereafter.
PMID- 11008047
TI - Retinal breaks before and after neodymium:YAG posterior capsulotomy.
AB - PURPOSE: To determine the frequency of asymptomatic retinal breaks before and
after neodymium:YAG (Nd:YAG) laser posterior capsulotomy. SETTING: Department of
Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS:
Of 350 consecutive patients referred for their first laser Nd:YAG posterior
capsulotomy, 235 eligible eyes were enrolled and 220 eyes completed the study. A
vitreoretinal surgeon looked for retinal breaks using binocular indirect
ophthalmoscopy with scleral indentation. The eyes were examined 1 week before and
1 hour and 1 month after the posterior capsulotomy. The number, type, and
location of retinal breaks were recorded. RESULTS: The median age of eligible
patients who did not participate in the study was higher than that of enrolled
patients (79.6 versus 74.4 years; P =.0005). The mean axial length, median time
from cataract surgery, and the course of cataract surgery were comparable in both
groups. Before the posterior capsulotomy, an untreated retinal break was
diagnosed in 4 of the 235 eyes (1.7%; 95% confidence interval [CI] 0 to 4)
scheduled for surgery and an undiagnosed retinal detachment was present in 2
additional eyes (0.9%; 95% CI 0 to 3). An asymptomatic retinal break was also
present in 4 fellow eyes (1.7%, 95% CI 0 to 4). No new breaks developed during
Nd:YAG posterior capsulotomy using a median total energy of 51 mJ (range 10 to
901 mJ) and a median number of 22 applications (range 4 to 341 applications) and
resulting in an opening with a median largest diameter of 3.4 mm (range 2.0 to
4.6 mm). In 1 treated eye (0.4%; 95% CI 0 to 2), a new retinal break had
developed by 1 month postoperatively. CONCLUSIONS: The observed 2.1% frequency of
asymptomatic retinal breaks that had escaped the attention of the referring
ophthalmologist or had developed by 1 month after Nd:YAG posterior capsulotomy
can be contrasted with the 0.5% to 2.0% frequency of retinal detachment reported
in the literature. However, it is not known which proportion of such asymptomatic
breaks, if any, will progress to detachment after Nd:YAG laser posterior
capsulotomy.
PMID- 11008048
TI - Diplopia after cataract surgery.
AB - PURPOSE: To evaluate the cause of diplopia after cataract surgery. SETTING:
Cataract surgery at 7 hospitals and examination of diplopia at a central eye
hospital. METHODS: This study comprised 18 eyes of 17 patients with diplopia that
developed after cataract surgery in which retrobulbar anesthesia was used. The
Hess screen test was done to diagnose oculomotor dysfunction. RESULTS: Several
cases showed superior or inferior deviation of the globe, but most patients had
nonuniform disturbances of eye movement. Examination of 3 patients by the Hess
chart within 1 week after surgery showed paralysis of eye muscles but an
overaction at a later stage, evident by reversal of eye position 1 month later.
Surgery for strabismus was performed in 6 cases. One case with diplopia improved
spontaneously 3 months after cataract surgery and achieved good alignment.
CONCLUSIONS: The Hess screen test was useful for comparing changes in oculomotor
function before and after surgery. Oculomotor dysfunction after cataract surgery
may be caused directly by traumatic injury during administration of anesthesia or
surgery using bridle sutures or indirectly from sensitivity to anesthetic agents.
PMID- 11008049
TI - Incidence of ocular misalignment and diplopia after uneventful cataract surgery.
AB - PURPOSE: To evaluate the incidence of ocular misalignment and diplopia after
uneventful cataract surgery. SETTING: An outpatient private practice eye
institute. METHODS: One hundred thirty-eight patients referred to 1 cataract
surgeon were prospectively evaluated. Orthoptic evaluations were performed within
1 month before and then 1 day, 1 week, and 1 month after cataract surgery.
Anesthesia was by retrobulbar injection, and cataract extraction was done by
phacoemulsification. RESULTS: Cataract surgery was performed in 118 patients.
Preoperatively, 16 patients had ocular misalignment; 10 were phoric, 4 were
intermittently tropic, and 2 were tropic. Follow-up evaluation was obtained for
101 patients (86%) at 1 day, 91 (77%) at 1 week, and 88 (75%) at 1 month. A
change in ocular alignment occurred in 22 of 101 patients (22%) at 1 day, 9 of 91
(10%) at 1 week, and 6 of 88 (7%) at 1 month. Only 1 patient who had a change in
alignment at 1 month was symptomatic. CONCLUSIONS: A persistent change in ocular
alignment after uneventful cataract surgery occurred in 7% of patients. However,
symptomatic diplopia was uncommon (1 in 118; 0.85%) in this relatively small
series.
PMID- 11008050
TI - Phacoemulsification in eyes with a small pupil.
AB - PURPOSE: To evaluate the intraoperative difficulties and long-term outcome of
phacoemulsification through a small pupil using minimal iris manipulation.
SETTINGS: Iladevi Cataract & IOL Research Centre, Ahmedabad, India. METHODS: This
prospective study included 30 consecutive eyes with a maximally dilated pupil
size of 4.0 mm or smaller. Except synechiolysis and occasional pupil retraction
with a chopper, no iris manipulation was performed. The phacoemulsification
technique included creation of deep central space, use of a low aspiration flow
rate with appropriate vacuum, and step-by-step chop in situ and lateral
separation of the nucleus. Patients were examined 1 day, 1 week, 1 and 3 months,
and 1 year postoperatively. Specular microscopy was performed at 1 month and 1
year. RESULTS: Fourteen eyes had chronic iritis, 12 had glaucoma surgery, 2 had
pseudoexfoliation, and 2 had a rigid pupil. Mean follow-up was 13.6 months.
Eighteen eyes (60%) had hard cataract. Mean preoperative pupil size was 2.80 mm
+/- 0.75 (SD). Mean pupil size before the capsulorhexis was initiated was 4.42 +/
0.58 mm. The iris was bruised in 10 eyes during cortex removal. Trace amounts of
cortex were left in 4 cases. Two eyes had increased intraocular pressure in the
early postoperative period. Six patients had a minimal amount of retained
viscoelastic material (pseudofibrin), and 2 patients developed a sterile
hypopyon. Sixteen eyes had cell deposits on the IOL surface and 12 eyes, fine
uveal pigments. In 2 eyes with previous glaucoma surgery and in all eyes with
iritis except 2, posterior synechias reformed. CONCLUSIONS: Successful
phacoemulsification was done with minimal or no pupil-widening maneuvers,
restoring the preoperative pupil configuration.
PMID- 11008051
TI - Surgical management of congenital cataract associated with severe microphthalmos.
AB - PURPOSE: To report the results of cataract surgery in children with severe
microphthalmos and congenital cataract. SETTING: Seoul National University,
Department of Ophthalmology, Seoul, Korea. METHODS: Retrospective studies were
conducted by reviewing the charts of 20 eyes of 11 patients with severe
microcornea and microphthalmos or severe microcornea with a corneal diameter
smaller than 9.0 mm. The patient pool was divided according to surgical method,
specifically by incision site: an anterior group that had corneal limbal
incisions and a posterior group treated via pars plicata incisions. Preoperative
examinations included bilaterality, corneal diameter, axial length, and eye and
systemic abnormalities. Postoperative results and complications of the 2
operative methods were compared. RESULTS: All 11 patients had bilateral
congenital cataract and microphthalmos. Except in 1 case, surgeries were done in
patients ranging in age from 2 to 16 months. Mean follow-up was 2 years. Corneal
diameter was smaller than 9.0 mm in all 20 eyes and smaller than 7.5 mm in 11
eyes. Ten eyes were categorized into the anterior group, and the other 10 eyes
were placed in the posterior group. Postoperative complications included
secondary membranes in 3 eyes in the posterior group and corneal opacity in 3
eyes in the anterior group. CONCLUSION: The surgical management of children with
congenital cataract and severe microphthalmos is recommended as a way to improve
vision but must be performed carefully to avoid complications.
PMID- 11008052
TI - Acular as a single agent for use as an antimiotic and anti-inflammatory in
cataract surgery.
AB - PURPOSE: To assess the safety and effectiveness of ketorolac tromethamine 0. 5%
(Acular) as a cost-efficient single agent to prevent intraoperative miosis and
postoperative inflammation in cataract surgery. METHODS: Both eyes of 26 patients
were randomized to receive Acular preoperatively and postoperatively or
flurbiprofen sodium (Ocufen) preoperatively and prednisolone acetate 1% (Pred
Forte) postoperatively. Time scheduled between procedures was from 2 weeks to 1
month. Pupil dilation was measured preoperatively, intraoperatively, and at the
end of surgery. Cell and flare were measured 1 day, 1 week, and 1 month
postoperatively. RESULTS: A comparison of the Acular and the Ocufen/Pred Forte
groups (n=22) showed no statistically significant differences in dilation
(preoperative versus postpostoperative) or cell and flare postoperatively.
CONCLUSIONS: Using Acular as a single agent was as effective as the combination
of preoperative Ocufen and postoperative Pred Forte in preventing intraoperative
miosis and postoperative inflammation in cataract surgery. The use of Acular as a
single agent could save the expense of using separate anti-inflammatory and
antimiotic preparations preoperatively and postoperatively, enhancing convenience
for the surgeon and surgical facility.
PMID- 11008053
TI - Gentian violet solution for staining the anterior capsule.
AB - PURPOSE: To evaluate the histopathological changes after injecting gentian violet
solution into the anterior chamber of rats and to describe a technique that uses
gentian violet to allow a clear view of the anterior capsule during continuous
curvilinear capsulorhexis (CCC) in human eyes with white mature cataract.
SETTING: Department of Ophthalmology, University of Dicle, Diyarbakir, Turkey.
METHODS: In this masked, experimental study (first stage), 0.05 mL of gentian
violet 0.01% or 0.001% solution or balanced salt solution (BSS) (control group)
was injected into the anterior chamber of 30 eyes of 30 Wistar albino rats. One,
24, and 48 hours after injection, 4 eyes in each group and 2 eyes in the control
group were enucleated, and histopathological examination was performed. In the
second stage, these solutions were used for staining the anterior capsule in the
18 human eyes with white mature cataract. The success rate of CCC and
intraoperative and postoperative complications were evaluated. RESULTS:
Histopathological examination revealed no pathology in any group. A CCC was
completed in all cases. No intraoperative or postoperative complications were
observed in human eyes except mild corneal edema and mild inflammatory reaction
in the anterior chamber that improved within 1 week. Mean follow-up was 3.4
months. Visualization of the anterior capsule was better with gentian violet
0.01% solution. CONCLUSIONS: Gentian violet solutions at 0.01% and 0.001%
concentrations had no evident toxic effect that caused significant
histopathological changes. The staining technique was practical and helped the
surgeon visualize the anterior capsule. However, gentian violet may have adverse
effects that lead to corneal edema.
PMID- 11008054
TI - Clinical results using the Holladay 2 intraocular lens power formula.
AB - PURPOSE: To analyze the accuracy of the Holladay 2 formula, which has been
proposed as an improvement over the original Holladay formula. METHODS: This
retrospective analysis comprised 317 eyes operated on by 1 surgeon using 1
technique and 1 intraocular lens style in a specialty practice. Because the
Holladay 2 formula has yet to be published, its accuracy can only be analyzed
using the commercially available Holladay IOL Consultant computer program to
compare it to the Holladay 1, Hoffer Q, and SRK/T formulas. Defined axial length
ranges were analyzed individually. RESULTS: A lower mean absolute error (MAE)
trend was found for the average length eye (22.0 to 24.5 mm) by the Holladay 1
and Hoffer Q formulas. For short eyes (< 22.0 mm), the Hoffer Q and Holladay 2
perform better. The SRK/T consistently showed a trend toward the lowest MAE in
all long eyes (>24.5 mm) as well as the subdivisions of medium long (24.5 to 26.0
mm) and very long (>26.0 mm). The Holladay 2 trended toward the least accurate
(MAE) of the 4 formulas in all ranges of axial length except the shortest and the
very longest. It appears to perform poorer in average and medium long eyes.
CONCLUSIONS: Although the Holladay 2 formula has improved its MAE accuracy in
short eyes, it was not more accurate than the Hoffer Q. The changes made in the
formula to effect this improvement in MAE seem to have sacrificed the accuracy of
the original Holladay formula in eyes with average and medium long axial lengths.
PMID- 11008055
TI - Potential acuity meter accuracy in cataract patients.
AB - PURPOSE: To determine potential acuity meter (PAM) accuracy in patients with
cataract as the only ocular disease. SETTING: Hospital de Clinicas de Porto
Alegre, Brazil. METHODS: This prospective study comprised 74 eyes with cataract.
Patients with other ocular pathology diagnosed before or after surgery, as well
as those with complicated surgeries, were excluded. All patients had PAM
evaluation before surgery; these results were compared to the final postoperative
visual acuity. Patients were divided into 4 cataract groups based on the Lens
Opacity Classification System II: Group 1, early cataracts (nuclear opalescence
[NO] 1 and/or posterior subcapsular cataracts [P] 1 and/or cortical opacity [C] <
2); Group 2, definite cataracts (NO2 and/or C2, with or without P1); Group 3,
posterior cataracts (P2 or P3); Group 4, mature cataracts (N3 and/or C > or = 3,
with or without P1). The PAM result was considered accurate if it was within 2
lines of the postoperative best spectacle-corrected visual acuity (BSCVA) 3
months after surgery. RESULTS: All patients had a BSCVA of 20/20. Accuracy of the
PAM was 58.3% in Group 1, 50.0% in Group 2, 27.8% in Group 3, and 6.7% in Group 4
(P =.000 017). Patient age did not influence the results. CONCLUSIONS: The PAM
may be used as a complementary tool in evaluating early and nondense cataracts;
however, patients should not be excluded as candidates for cataract surgery based
solely on PAM results.
PMID- 11008056
TI - Osmolality of various viscoelastic substances: comparative study.
AB - PURPOSE: To determine the osmolality of various viscoelastic substances. SETTING:
Department of Ophthalmology, Johannes Gutenberg-University, Mainz, and Institute
for Medical Device Testing, Memmingen, Germany. METHODS: The analysis was carried
out according to the European Pharmacopoeia by means of a calibrated osmometer
using the freezing-point depression method. Each syringe was analyzed as a
duplicate analysis. RESULTS: Mean osmolalities (mOsmol/kg) of the sodium
hyaluronate viscoelastic substances were Allervisc 299; Allervisc Plus 307;
Amvisc Plus 335; AMO Vitrax 284; Biolon 279; Dispasan 311; Dispasan Plus 314;
Healon 295; Healon GV 312; Healon5 322; HYA-Ophtal 376; Microvisc 313; Microvisc
Plus 341; Provisc 307; Rayvisc 312; Viscoat 340; Visko 296; Visko Plus 319. Mean
osmolarities of the hydroxypropyl methylcellulose viscoeslatic substances were
Adatocel 278; HPMC Ophtal L 358; HPMC Ophtal H 360; La Gel 317; OcuCoat 309;
Visco Shield 376. CONCLUSIONS: There were significant differences in osmolality
among viscoelastic substances, which may explain the differences in corneal
thickness after cataract surgery. A viscoelastic substance with an osmolality of
305 mOsmol/kg or slightly higher is preferable, especially in patients with a
compromised corneal endothelium.
PMID- 11008057
TI - Intraocular pressure development in the rabbit eye after aqueous exchange with
ophthalmic viscosurgical devices.
AB - PURPOSE: To evaluate an animal model used to study intraocular pressure (IOP)
development after aqueous exchange with several commercially available ophthalmic
viscosurgical devices (OVDs). SETTING: Department of Preclinical Ophthalmology,
Pharmacia & Upjohn, Uppsala, Sweden. METHODS: Albino rabbits (New Zealand White)
were used. Aqueous humor (50 microL) was exchanged with 8 OVDs. The IOP was
measured every second hour for 12 hours and then 24, 48, and 72 hours after
aqueous exchange using a pneumotonometer (Modular One, Bio-Rad Digilab Inc). A
minimum of 7 eyes was used for each OVD. Healon was used as control in 1 eye in
all experiments. The OVDs were Viscoat (chondroitin sulfate-sodium hyaluronate),
Provisc (sodium hyaluronate), Biolon (sodium hyaluronate), Healon GV, Healon5,
Ophthalin (sodium hyaluronate), Ocucoat (hydroxypropyl methylcellulose), and
Ivisc (sodium hyaluronate). RESULTS: All OVDs caused a postoperative increase in
IOP. At 24 hours, the IOP was at the preoperative levels. However, there was
considerable variation in the maximum IOP value and when this value occurred. The
maximum value appeared to depend on the concentration of the rheologically active
substance in the product and the time of the average molecular mass. There was
also an increase in central corneal thickness, with a maximum increase 24 hours
after the exchange but a large variation among animals. CONCLUSION: The animal
model appears to be useful for comparing various OVDs, and the results may serve
as a guide for the design of clinical studies of new products.
PMID- 11008058
TI - Arteriovenous fistula induced by a peribulbar nerve block.
AB - Arteriovenous fistula (AVF) of the head and neck region is an uncommon clinical
condition that can be of congenital or acquired etiology. We report a case of AVF
of the left supraorbital vessels that developed after a peribulbar nerve block
was given for cataract surgery.
PMID- 11008059
TI - Black intraocular lens for leukocoria.
AB - We describe a 33-year-old man with leukocoria and no visual potential who
obtained an excellent cosmetic result after cataract extraction and implantation
of an intraocular lens with an entirely black optic.
PMID- 11008060
TI - Phacoemulsification in a patient with marked cervical kyphosis.
AB - A patient with long-standing ankylosing spondylitis and chronic uveitis needed
cataract extraction in his only eye. Extensive spinal deformities, including
cervical kyphosis, prevented him from being positioned satisfactorily for surgery
using a routine head-end or temporal position for the surgeon. The best possible
position for surgery was achieved using an orthopedic operating table, which
allowed the patient's head to be reclined to a position of 60 degrees to the
horizontal. Successful combined phacoemulsification and trabeculectomy was then
performed, although the angle of approach for the surgeon and the operating
microscope was awkward.
PMID- 11008061
TI - Dimerization of G-protein-coupled receptors: implications for drug design and
signaling.
PMID- 11008062
TI - Dimerization of G-protein coupled receptors.
PMID- 11008063
TI - Opioids and their complicated receptor complexes.
AB - No field more eagerly awaits a molecular clarification for G-protein coupled
receptor (GPCR) dimerization than the opioid receptor field. Extensive evidence
of pharmacological and functional interactions between opioid receptor types has
primed this field for such a resolution. In retrospect, much of the data
collected on synergy between different opioid receptor types may represent the
functional correlate for the newly found opioid receptor dimerization. While
previous reports of functional synergy have been, for the most part, consistent
in demonstrating cross-regulation between two receptor types, the lack of highly
receptor-selective ligands allowed skeptics to remain doubtful over the
interpretations of these results. Today, two important developments in the opioid
receptor field help reinvigorate the hypothesis of functional, cross-modulating
opioid receptor complexes: (1) The existence of highly selective ligands which
eliminate any possibility of cross-reactivity between receptor types, and (2) the
discovery that opioid receptors and a number of other GPCRs exist as dimers in
biochemical, functional and pharmacological assays. It is with these new tools
that we seek to understand the mechanisms and implications of dimerization.
Initial results of these studies have demonstrated that the dimerization of
opioid receptors may help consolidate several pharmacological findings that have
remained unanswered. In this review we present biochemical, pharmacological and
functional evidence for opioid receptor complexes and add evidence from our
recent studies on opioid receptor dimerization. We believe a thorough
understanding of receptor dimerization is crucial in clarifying the mechanism of
action of opioids and other drugs and may serve a more practical purpose in
aiding the development of novel therapeutic drugs.
PMID- 11008064
TI - Molecular aspects of muscarinic receptor dimerization.
AB - The five muscarinic acetylcholine receptors (M(1)-M(5)) are prototypical members
of the superfamily of G-protein-coupled receptors (GPCRs). During the past
decade, this laboratory has used different members of this receptor subfamily as
model systems to study the molecular mechanisms involved in GPCR function. This
article reviews recent investigations dealing with molecular aspects of M(3)
muscarinic receptor assembly and dimerization/oligomerization. Studies with
coexpressed M(3) receptor fragments and M(3) muscarinic/alpha(2C)-adrenergic
hybrid receptors showed that muscarinic receptors, like other GPCRs, are composed
of multiple autonomous folding domains. Moreover, biochemical studies have
provided direct evidence for the formation of M(3) receptor dimers/oligomers.
These high molecular mass receptor species are expressed on the cell surface and
can bind muscarinic ligands. M(3) receptor dimerization/oligomerization appears
to be receptor subtype-selective and involves both non-covalent interactions as
well as disulfide-crosslinking of receptor monomers. These studies add to the
growing number of reports suggesting the existence of GPCR dimers or multimers.
The precise functional characteristics of such receptor aggregates remain to be
elucidated.
PMID- 11008065
TI - Oligomerization of dopamine and serotonin receptors.
AB - Until recently, it has largely been assumed that G protein-coupled receptors
(GPCRs) function as monomeric entities. However, over the past few years, we and
others have documented that GPCRs can form dimers and oligomers, leading to a re
evaluation of the mechanisms thought to mediate GPCR function. Despite the
growing number of investigations into dimerization, little is known about the
structural basis of receptor-receptor interactions and the functional
consequences of dimer formation. Here, we present a brief review of some insights
we have gained into the dimerization of dopamine and serotonin receptors. We have
demonstrated that agonist-regulated trafficking is identical for receptor
monomers and dimers, however, agonist treatment appears to stabilise the receptor
oligomers. An investigation of the structural assembly between receptors involved
in dimerization showed that there are several sites of interaction including
hydrophobic transmembrane domain interactions and intermolecular disulphide
bonds. We have also examined receptor hetero-oligomerization and demonstrated the
potential for novel functions as a result of these associations. Finally, as a
result of these observations, we have been able to present evidence that GPCRs
function as oligomers in the cell.
PMID- 11008066
TI - Signal transduction by GABA(B) receptor heterodimers.
AB - GABA(B) receptors are G-protein-coupled receptors that mediate inhibition
throughout the central and peripheral nervous systems. A single cloned receptor,
GABA(B)R1, which has at least three alternatively spliced forms, appears to
account for the vast majority of binding sites in the brain for high-affinity
antagonists. In heterologous expression systems GABA(B)R1 is poorly expressed on
the plasma membrane and largely fails to couple to ion channels. A second gene,
GABA(B)R2, which exhibits moderately low homology to GABA(B)R1, permits surface
expression of GABA(B)R1 and the appearance of baclofen-sensitive K(+) and Ca(+1)
currents. We review the data that supports a model of the native GABA(B) receptor
as a heterodimer composed of GABA(B)R1 and GABA(B)R2 proteins. New data from
mutagenesis experiments are presented that point to amino acid residues on
GABA(B)R1 critical for ligand activation of the heterodimer. The possible role of
GABA(B)R2 in signal transduction is also discussed. The interdependent nature of
the two subunits for receptor function makes the GABA(B) receptor a useful model
to explore the larger significance of GPCR dimerization for G-protein activation.
PMID- 11008067
TI - Evidence for adenosine/dopamine receptor interactions: indications for
heteromerization.
AB - Evidence has been obtained for adenosine/dopamine interactions in the central
nervous system. There exists an anatomical basis for the existence of functional
interactions between adenosine A(1)R and dopamine D(1)R and between adenosine
A(2A) and dopamine D(2) receptors in the same neurons. Selective A(1)R agonists
affect negatively the high affinity binding of D(1) receptors. Activation of
A(2A) receptors leads to a decrease in receptor affinity for dopamine agonists
acting on D(2) receptors, specially of the high-affinity state. These
interactions have been reproduced in cell lines and found to be of functional
significance. Adenosine/dopamine interactions at the behavioral level probably
reflect those found at the level of dopamine receptor binding and transduction.
All these findings suggest receptor subtype-specific interactions between
adenosine and dopamine receptors that may be achieved by molecular interactions
(e.g., receptor heterodimerization). At the molecular level adenosine receptors
can serve as a model for homomeric and heteromeric protein-protein interactions.
A1R forms homodimers in membranes and also form high-order molecular structures
containing also heterotrimeric G-proteins and adenosine deaminase. The occurrence
of clustering also clearly suggests that G-protein- coupled receptors form high
order molecular structures, in which multimers of the receptors and probably
other interacting proteins form functional complexes. In view of the occurrence
of homodimers of adenosine and of dopamine receptors it is speculated that
heterodimers between these receptors belonging to two different families of G
protein-coupled receptors can be formed. Evidence that A1/D1 can form
heterodimers in cotransfected cells and in primary cultures of neurons has in
fact been obtained. In the central nervous system direct and indirect receptor
receptor interactions via adaptor proteins participate in neurotransmission and
neuromodulation and, for example, in the establishment of high neural functions
such as learning and memory.
PMID- 11008068
TI - Dimerization and domain swapping in G-protein-coupled receptors: a computational
study.
AB - In recent years there has been an increasing number of reports describing G
protein-coupled receptor (GPCR) dimerization and heterodimerization. However, the
evidence on the nature of the dimers and their role in GPCR activation is
inconclusive. Consequently, we present here a review of our computational studies
on G protein-coupled receptor dimerization and domain swapping. The studies
described include molecular dynamics simulations on receptor monomers and dimers
in the absence of ligand, in the presence of an agonist, and in the presence of
an antagonist (or more precisely an inverse agonist). Two distinct sequence-based
approaches to studying protein interfaces are also described, namely correlated
mutation analysis and evolutionary trace analysis. All three approaches concur in
supporting the proposal that the dimerization interface includes transmembrane
helices 5 and 6. These studies cannot distinguish between domain swapped dimers
and contact dimers as the models used were restricted to the helical part of the
receptor. However, it is proposed that for the purpose of signalling, the domain
swapped dimer and the corresponding contact dimer are equivalent. The
evolutionary trace analysis suggests that every GPCR family and subfamily (for
which sufficient sequence data is available) has the potential to dimerize
through this common functional site on helices 5 and 6. The evolutionary trace
results on the G protein are briefly described and these are consistent with GPCR
dimerization. In addition to the functional site on helices 5 and 6, the
evolutionary trace analysis identified a second functional site on helices 2 and
3. Possible roles for this site are suggested, including oligomerization.
PMID- 11008069
TI - Expression of proinflammatory cytokines in the failing human heart: comparison of
recent-onset and end-stage congestive heart failure.
AB - BACKGROUND: Plasma levels of proinflammatory cytokines, including tumor necrosis
factor (TNF)-alpha and interleukin (IL)-6, are elevated in patients with
congestive heart failure (CHF). Recent studies suggest that the failing human
heart is a source of proinflammatory cytokines in the end-stage failing heart.
However, the relevance of plasma levels to those of the myocardium remains
undefined. We sought to compare cytokine expression in early and end-stage CHF,
and to evaluate the correlation of tissue expression to plasma levels. METHODS:
Two patient populations were studied: patients with recent-onset CHF, all with
symptoms less than 6 months (n = 17, duration of symptoms 2.1 +/- 1.6 months,
range of New York Heart Association (NYHA) 1 to 3), and end-stage heart-failure
patients (n = 7) who underwent left-ventricular assist-device (LVAD) implantation
(Duration of symptoms 47.1 +/- 28.0 months, all NYHA class 4). Plasma levels of
TNF-alpha and IL-6 proteins were evaluated by an Enzyme-Linked Immuno-Sorbent
Assay (ELISA), while myocardial levels of cytokine transcripts were assessed by
ribonuclease (Rnase) protection assay. RESULTS: In patients with end-stage heart
failure, TNF-alpha and IL-6 were increased in the plasma as well as in the
myocardium (plasma: TNF-alpha = 7.7 +/- 2.3 pg/ml, IL-6 = 45.0 +/- 47.1 pg/ml;
myocardium: TNF-alpha = 0.31 +/- 0.15% of glyceraldehyde 3-phosphate
dehydrogenase (GAPDH) expression, IL-6 = 1.56 +/- 1.54% ). In contrast, despite
elevated plasma levels of TNF-alpha and IL-6, the myocardium of patients with the
recent onset of symptoms demonstrated minimal expression of TNF-alpha and IL-6
messenger ribonucleic acid (mRNA) (plasma: TNF-alpha = 4.3 +/- 1.7 pg/ml, IL-6 =
3.3 +/- 1.8 pg/ml; myocardium: TNF-alpha = 0.13 +/- 0. 04%, IL-6 = 0.02 +/-
0.04%). Plasma levels of TNF-alpha were significantly correlated with those in
the myocardium when both populations were combined. (r = 0.69, p < 0.001).
CONCLUSIONS: Cytokines are expressed in the myocardium in end-stage heart failure
to a much greater degree than in patients with the recent-onset of symptoms. This
suggests that induction of cytokines in the myocardium is a relatively late event
in the pathogenesis of CHF. Furthermore, plasma levels of TNF-alpha correlates
with mRNA expression in the myocardium and thus may serve as an appropriate
marker of myocardial cytokine activation. Whether the production of cytokines in
the failing human heart precedes the elevation of cytokines in the plasma remains
undefined. Therefore, we studied expression of TNF-alpha and IL-6 in the
myocardium as well as in the plasma in patients with early and end-stage CHF. The
results have demonstrated that cytokines are expressed in the myocardium in end
stage heart failure to a much greater degree than in patients with the recent
onset of symptoms. This suggests that induction of cytokines in the myocardium is
a relatively late event in the pathogenesis of CHF.
PMID- 11008070
TI - Growth and pubertal development following pediatric heart transplantation: a 15
year experience at Ste-Justine Hospital.
AB - BACKGROUND: Thirty-one children and adolescents have undergone allograft heart
transplantation at Ste-Justine Hospital from July 1984 to August 1996. Twenty
five patients were followed prospectively more than 3 years to document their
growth and pubertal development. METHODS: Parameters surveyed were clinical
(height, weight, pubertal staging, and bone age) and biochemical (luteinizing
hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol,
dehydroepiandrosterone sulphate (DHEAS), IGF-1, and fasting insulin). RESULTS: At
surgery, there were 18 boys and 7 girls aged 11 months to 17 years (median 13
years); 14 had congenital heart defects (CHDs) and 11 had a cardiomyopathy (CM).
Immunosuppressive therapy included cyclosporine, azathioprine, and prednisone.
Eighteen patients were still growing (15 boys, 3 girls): 8 had a retarded bone
age and 6 with CHD had severe growth failure. Following surgery, most patients
maintained their height within one sodium dodecyl sulfate (SDS) score of that
initially observed. Patients reaching their target heights do so mainly in the
lower range. Three patients not reaching target height had a CHD. Weight was
greatest 1 year postoperatively (113 +/- 27% ideal body weight) with
normalization at 2 years (100 +/- 18%). Of the 13 prepubertal patients, menarche
occurred at age 12 in 1 girl, while 3 boys began puberty at age 12 years. In both
sexes, serum levels of gonadotropins and IGF-1 increased during puberty, moderate
hyperinsulinism was observed, and DHEAS levels decreased. CONCLUSIONS: Our
results indicate that children and adolescents grow normally following cardiac
transplantation and that they attain their target height despite a lack of catch
up growth. They gain weight significantly in the first postoperative year with
normalization of their weight at 2 years. Furthermore, the clinical and
biochemical indices of puberty are overall within the norms. However, the
severity of growth delay at the time of transplantation inherent to the cardiac
pathology has a major impact on adult height.
PMID- 11008071
TI - Utility of extracorporeal membrane oxygenation for early graft failure following
heart transplantation in infancy.
AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is widely used for
postcardiotomy cardiogenic shock in children. However, the efficacy of ECMO for
early post-heart transplant graft failure in infants has not been reported. Our
aims were to determine: (1) the utility of ECMO in infants with severe donor
heart dysfunction, (2) predictors for requiring ECMO, and (3) the long-term
outcome of surviving ECMO patients. METHODS: All infants (age < 6 months at
listing) undergoing heart transplantation were reviewed. Diagnostic categories
were hypoplastic left heart syndrome (HLHS) and non-HLHS (complex congenital
heart disease and cardiomyopathies). Continuous and categorical comparisons were
by Wilcoxon's rank sum test and Fisher's exact test respectively. RESULTS: 14 (12
HLHS, 2 non-HLHS) of 63 (46 HLHS, 17 non-HLHS) infants were placed on ECMO. Ten
patients (71%) were successfully weaned from ECMO and 8 (57%) were discharged
alive. All ECMO hospital survivors remain alive (mean follow-up 36.2 +/- 21.4
months, range 13.1-77.6 months). Mean duration of ECMO support was 68 hours in
weaned patients vs 144 hours (p = 0.19) in nonweaned patients, and 64 hours in
survivors vs 123 hours (p = 0.35) in nonsurvivors. ECMO deaths were due to sepsis
(n = 3), intractable pulmonary hypertension (n = 2), and intracranial bleed (n =
1). Neurologic deficits occurred in 2 survivors. Median ICU and hospital stays
for ECMO survivors were 29 and 33 days vs 7 (p = 0.0003) and 9 (p = 0.0004) days
for non-ECMO patients. Age listed, age transplanted, wait time, body weight,
donor/recipient weight ratio, total ischemia time, and diagnosis did not predict
the need for ECMO. CONCLUSIONS: (1) ECMO is useful for post-heart transplant
circulatory support in infants with early graft failure. (2) All survivors were
weaned in fewer than 4 days. (3) Three-year survival of ECMO hospital survivors
has been high, but neurologic complications are prevalent.
PMID- 11008072
TI - Glucocorticoid-induced osteopenia in adolescent heart transplant recipients.
AB - BACKGROUND: Glucocorticoid-induced cushingoid symptoms, including osteopenia and
osteoporosis are well-documented in adult heart transplant recipients (HTR). Bone
mineral density (BMD) of the axial skeleton is diminished by 10% to 20% within 60
days after transplantation (Tx) and most adult HTR fulfill World Health
Organization criteria for osteoporosis (BMD > 2.5 SD below norm). At present, we
do not know whether glucocorticoids have similar deleterious effects in
adolescent HTR. METHODS: To determine the consequences of glucocorticoid
immunosuppression on regional bone mineral density (BMD) and biochemical markers
of bone metabolism in adolescent HTR, we studied 19 patients (aged 16 +/- 3) at
19 months (group mean) after Tx. We measured BMD (hydroxyapatite g/cm(2)) of the
total body, lumbar spine, and pelvis using dual-energy X-ray absorptiometry
(Lunar). Serum levels of bone-specific alkaline phosphatase and pyridinoline
cross-links were determined by enzyme immunoassay in serum kits. RESULTS: The BMD
of the lumbar spine (-12%), femur neck (-13%), femur trochanter (-12%), and
ward's triangle (-16%) were significantly (p < 0.05) lower in adolescent HTR than
age- and gender-matched norms. Serum levels of alkaline phosphatase (29 +/- 6 vs
22 +/- 3 U/liter) and pyridinoline cross-links (5.3 +/- 1.1 vs 3.8 +/- 0.7
mmol/liter) were significantly (p < 0.05) elevated in adolescent HTR, compared
with age- and gender-matched controls studied in our laboratory. CONCLUSIONS: Our
cross-sectional results demonstrate that BMD of the axial skeleton in adolescent
HTR is significantly lower (-10% to 20%) than age-matched norms and that serum
biochemical markers of bone metabolism are significantly elevated, suggesting
accelerated bone turnover.
PMID- 11008073
TI - Lung allocation in the United States, 1995-1997: an analysis of equity and
utility.
AB - BACKGROUND: Waiting time for organ transplantation varies widely between programs
of different sizes and by geographic regions. The purpose of this study was to
determine if the current lung-allocation policy is equitable for candidates
waiting at various-sized centers, and to model how national allocation based
solely on waiting time might affect patients and programs. METHODS: UNOS provided
data on candidate registrations; transplants and outcomes; waiting times; and
deaths while waiting for all U.S. lung-transplant programs during 1995-1997.
Transplant centers were categorized based on average yearly volume: small (< or =
10 pounds sterling transplants/year; n = 46), medium (11-30 transplants/year; n =
29), or large (>30 transplants/year; n = 6). This data was used to model national
organ allocation based solely on accumulated waiting time for candidates listed
at the end of 1997. RESULTS: Median waiting time for patients transplanted was
longest at large programs (724-848 days) compared to small and medium centers
(371-552 days and 337-553 days, respectively) and increased at programs of all
sizes during the study period. Wait-time-adjusted risk of death correlated
inversely with program size (365 vs 261 vs 148 deaths per 1,000 patient-years-at
risk at small, medium, and large centers, respectively). Mortality as a
percentage of new candidate registrations was similar for all program categories,
ranging from 21 to 25%. Survival rates following transplantation were equivalent
at medium-sized centers vs large centers (p = 0.50), but statistically lower when
small centers were compared to either large- or medium-size centers (p < or =
0.05). Using waiting time as the primary criterion lung allocation would acutely
shift 10 to 20% of lung-transplant activity from medium to large programs.
CONCLUSIONS: 1) Waiting list mortality rates are not higher at large lung
transplant programs with long average waiting times. 2) A lung-allocation
algorithm based primarily on waiting-list seniority would probably disadvantage
candidates at medium-size centers without improving overall lung-transplant
outcomes. 3) If fairness is measured by equal distribution of opportunity and
risk, we conclude that the current allocation system is relatively equitable for
patients currently entering the lung-transplant system.
PMID- 11008074
TI - The utility of open lung biopsy following lung transplantation.
AB - BACKGROUND: Most pulmonary complications associated with lung transplantation
have non-specific clinical characteristics. Furthermore, common diagnostic
modalities, including bronchoscopy with transbronchial biopsy (TBB), often do not
render a definitive diagnosis. In this study, we reviewed our experience with
open lung biopsy (OLB) following lung transplantation, specifically regarding its
ability to safely provide clinically relevant information that affects
therapeutic decisions. METHODS: From October 1989 to March 2000, 202 patients
underwent lung transplantation at our institution. We reviewed the clinical
course of the 42 patients who received 48 OLBs. Of these patients, we determined
the pre-operative clinical condition, preceding TBB histologic information, OLB
histology, treatment changes, and procedural complications as a result of the
OLB. RESULTS: A new, clinically unsuspected diagnosis was made in 14 biopsies
(29% of all OLB), and all of these resulted in therapy changes. Thirty-two
biopsies (67% of all OLB) confirmed our clinical suspicions, and new therapy was
initiated in 30 of these patients. Two patients (4% of all OLB) had non
diagnostic OLB. Four biopsies (8% of all OLB), including the 2 non-diagnostic
OLBs, did not result in any therapy changes or initiation of new therapy.
Complications occurred in 3 patients, all of whom had an air leak for >7 days.
CONCLUSION: Open lung biopsy in lung transplant patients renders a new,
unsuspected diagnosis in nearly one third of patients and leads to specific,
directed therapy in the vast majority of patients. Open-lung biopsy can be
performed safely and should be considered when diagnosis is uncertain in
clinically deteriorating patients.
PMID- 11008075
TI - Increased expression of inflammatory cytokines and adhesion molecules by alveolar
macrophages of human lung allograft recipients with acute rejection: decline with
resolution of rejection.
AB - BACKGROUND: Alveolar macrophages (AM) are the major population in bronchoalveolar
lavage (BAL) cells; we assessed their role in human lung allograft recipients by
correlating the expression of adhesion molecules and inflammatory cytokines with
clinical outcome of allograft. METHODS: We obtained BAL samples from patients and
enriched them for AM in plastic petri dish for 2 hours at 37 degrees C in 5%
CO(2). Expression of intercellular adhesion molecule-1 (ICAM-1, CD54), platelet
endothelial cell adhesion molecule-1 (PECAM-1, CD31), and CD11c was assessed by
flow cytometry using monoclonal antibodies. We assessed cytokine profile using
Multi-Probe RNase protection assay. RESULTS: Alveolar macrophages that express
CD11c, CD31 and CD54 were increased in patients with either rejection or
infection compared with those without rejection and infection. The difference in
the percentage of AM expressing CD11c and CD31 between the rejection group and
patients without rejection and infection group was statistically significant
(CD11c, p < 0.01; CD31, p < 0.03). Interleukin (IL)-1 alpha, IL-1 beta, IL-1
receptor antagonist (IL-1Ra), and IL-6 expression was higher in the rejection
group than in patients without rejection. Five out of 9 patients in the rejection
group expressed high levels of IL-15 and tumor necrosis factor-alpha compared
with patients without rejection and infection. The increased number of AM
expressing adhesion molecules and elevated expression of cytokines observed
during acute rejection declined to basal levels after successful treatment and
resolution of rejection. This study demonstrates that lung allograft rejection is
associated with increased expression of adhesion molecules and inflammatory
cytokines by AM, which could facilitate mononuclear cell adhesion and
extravasation contributing to the allograft injury in lung transplant recipients.
PMID- 11008076
TI - Renal failure after clinical heart transplantation is associated with the TGF
beta 1 codon 10 gene polymorphism.
AB - BACKGROUND: To determine whether genetic factors are involved in the development
of renal dysfunction due to cyclosporine nephrotoxicity, we analyzed 2
polymorphisms in the signal sequence of the transforming growth factor (TGF)-beta
1 gene; codon 10 (Leu(10) --> Pro) and codon 25 (Arg(25) --> Pro). METHOD: Using
sequence specific oligonucleotide probing, we analyzed both TGF-beta1 gene
polymorphisms in cardiac allograft recipients (n = 168) who survived at least 1
year with minimal follow-up of 7 years. Patients received cyclosporine and
steroids as maintenance immunosuppressive therapy. Renal dysfunction was defined
as a serum creatinine > or = 250 micromol/liter. RESULTS: Renal dysfunction was
observed in 2% (3/168) of the patients at 1 year, in 7% (11/160) at 3 years, in
12% (18/152) at 5 years, and in 20% (26/131) at 7 years post-transplantation. The
genotypic distributions for TGF-beta1 codon 10 were 7% Pro/Pro, 61% Pro/Leu, and
32% Leu/Leu, and for codon 25 these percentages were 1% Pro/Pro, 12% Pro/Arg, and
87% Arg/Arg. We found an association between the TGF-beta 1 genotype encoding
proline at codon 10 and renal dysfunction. At 7 years post-transplantation, 26%
(23/89) of the patients with the heterozygous Pro/Leu or homozygous Pro/Pro
genotype had renal dysfunction vs only 7% (3/42) of the patients with the
homozygous Leu/Leu genotype (p = 0.017). For the TGF-beta1 codon 25 genotypes, we
found no association between TGF-beta 1 genotypes and renal dysfunction.
CONCLUSION: Our data support the hypothesis that TGF-beta 1 is involved in the
process leading to renal insufficiency in cyclosporine-treated cardiac allograft
recipients. In these patients the presence of TGF-beta 1 Pro(10) might be a risk
factor.
PMID- 11008077
TI - Myocardial perfusion scintigraphy as a screening method for significant coronary
artery stenosis in cardiac transplant recipients.
AB - BACKGROUND: Several studies have explored the feasibility of using myocardial
perfusion imaging to detect allograft vasculopathy after heart transplantation.
We undertook the present prospective consecutive study to comparatively evaluate
the role of serial myocardial perfusion single-photon emission computed
tomography (SPECT) scanning and coronary arteriography (CAG) in detecting
coronary artery stenosis suitable for coronary angioplasty in heart transplant
recipients. METHODS: Within a 2-week interval during a follow-up period of 5.6
(95% confidence limits 2.1 to 12) years, 255 serial CAGs and myocardial perfusion
scintigraphies were performed in 67 patients. Arteriography and scintigraphy were
performed once yearly after heart transplantation. We retrospectively analyzed
the data. RESULTS: Myocardial scintigraphy showed pathologic reversible defects
in 9 out of 67 patients. Four of these patients had significant (>50% and also
>70%) focal segmental stenosis in the middle and proximal parts of the coronary
arteries (Type A lesions), 1 had diffuse and circumferential narrowing in the
distal parts (Type B lesions), whereas CAG showed no lesions in the remaining 4
patients. The patients with significant Type A lesions were revascularized with
percutaneous coronary angioplasty. Coronary arteriography showed that 1 patient
had extensive Type A and Type B lesions, whereas myocardial perfusion scans
detected no. The predictive value of a negative (normal) SPECT was 98% (95%
confidence limits 94% to 100%) for the detection of lesions suited for
revascularization. CONCLUSIONS: Annual myocardial SPECT seems well suited to
screen for significant coronary artery stenosis. A SPECT study without reversible
defects virtually excludes lesions suitable for coronary artery
revascularization.
PMID- 11008078
TI - FR167653 ameliorates pulmonary damage in ischemia-reperfusion injury in a canine
lung transplantation model.
AB - BACKGROUND: Interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha) are
recognized as important factors in ischemia-reperfusion (I/R) injury. FR167653
has been characterized as a potent suppressant of IL-1 and TNF-alpha production.
We previously reported that FR167653 suppressed the expression of IL-1 beta mRNA
after reperfusion and ameliorated pulmonary I/R injury following 3-hour left lung
warm ischemia in dogs. The aim of this study was to investigate the effects of
FR167653 on I/R injury in a canine left, single, lung transplantation model.
METHODS: We used 10 pairs of weight-matched dogs. We assigned 5 pairs to the FR
group, in which each animal received FR167653 (1 mg/kg/hr) IV from 30 minutes
before ischemia until 2 hours after reperfusion; we treated the transplanted
lungs with FR167653 after the onset of reperfusion. The others were assigned to
the control group. After 8-hour preservation with 4 degrees C Euro-Collins
solution, orthotopic left, single, lung transplantation was performed. During a 5
minute clamping test at the right pulmonary artery of each recipient, the left
(transplanted) pulmonary arterial pressure (L-PAP), left (transplanted) pulmonary
vascular resistance (L-PVR), arterial oxygen pressure (PaO(2)), and alveolar
arterial oxygen pressure difference (A-aDO(2)) were measured. We harvested
transplanted lung specimens for histologic study, and we counted
polymorphonuclear neutrophils (PMNs), which were identified by staining with
naphthol AS-D cholroacetate esterase. Pulmonary perfusion and ventilation
scintigraphy (Tc-99m-MAA and Xe-133) were performed. We observed the animals for
3 days after transplantation. RESULTS: The PAP, L-PVR, PaO(2), and A-aDO(2)
revealed significantly (p < 0.05) better function in the FR group than in the
control group. Histologically, lung edema was milder, and PMN infiltration was
significantly (p < 0.05) lower in the FR group than in the control group. Xe-133
and Tc-99m-MAA were widely distributed throughout the graft lung in the FR group.
Three-day survival rates in FR and control groups were 60% and 20%, respectively.
CONCLUSIONS: FR167653 appears to generate a protective effect on I/R injury in
lung transplantation in dogs.
PMID- 11008079
TI - Effects of EP4 solution and LPD solution vs Euro-Collins solution on Na(+)/K(+)
ATPase activity in rat alveolar type II cells and human alveolar epithelial cell
line A549 cells.
AB - BACKGROUND: Intact alveolar epithelial Na(+)/K(+)- adenosinetriphosphatase
(ATPase) function is important in preventing alveolar fluid accumulation after
lung transplantation. We examined whether the type of preservation solution used
influences Na(+)/K(+)-ATPase activity in alveolar epithelial cells. METHODS: Rat
alveolar type II cells were preserved with EP4, low-potassium dextran (LPD), or
Euro-Collins solution at 7 degrees C for 5 and 20 hours. To assess cell toxicity,
we measured cell viability and lactate dehydrogenase release. Na(+)/K(+)-ATPase
activity was measured as ouabain-sensitive ATPase hydrolysis. We also examined
the effect of terbutaline (10(-3) mol/liter) and dibutyryl cyclic adenosine
monophosphate (dbcAMP) (10(-3) mol/liter) on Na(+)/K(+)-ATPase activity in A549
cells preserved for 5 hours. RESULTS: All solutions caused significant damage of
rat alveolar type II cells at 20 hours. However, Na(+)/K(+)-ATPase activity was
preserved at normal levels with EP4 and LPD over 20 hours. Terbutaline and dbcAMP
significantly increased Na(+)/K(+)-ATPase activity in A549 cells preserved with
EP4 and LPD solutions for 5 hours. However, we observed no activation in the
cells preserved with Euro-Collins solution. We found no significant difference in
intracellular cAMP levels after terbutaline challenge among the types of
preservation solution. CONCLUSIONS: We conclude that extracellular-type solutions
such as EP4 and LPD may be preferable for maintaining not only the basal activity
but also the ability to activate Na(+)/K(+)-ATPase in response to beta-adrenergic
agonists, in alveolar epithelial cells.
PMID- 11008080
TI - Lung transplantation from dialysis dependent donors.
AB - Lung transplantation from a donor with chronic renal failure has never been
reported. This paper reports our successful experience with 2 transplants from
donors with end-stage renal disease who were on chronic hemodialysis, and reviews
the relevant literature on the effects of renal failure on pulmonary function and
on the use of marginal donors.
PMID- 11008081
TI - Orthotopic heart transplantation with concurrent aortic valve replacement and
coronary artery bypass grafting.
AB - We report a case of successful orthotopic heart transplantation of a donor heart
with normal ventricular function, 2-vessel coronary artery disease, and a
bicuspid aortic valve, which required concurrent aortic valve replacement and
coronary artery bypass grafting. In confronting the disparities in demand and
supply, we must consider the so-called marginally acceptable heart for either
critically ill recipients or those who may be disadvantaged on the waiting list.
PMID- 11008082
TI - Dactylaria gallopava infection presenting as a pulmonary nodule in a single-lung
transplant recipient.
AB - We describe the first case of a pulmonary nodule caused by Dactylaria gallopava
in a lung-transplant recipient. An asymptomatic lung-allograft recipient was
found to have a 2-cm nodule in the native lung 450 days after transplantation.
Culture of a transthoracic needle biopsy of the solitary pulmonary nodule
revealed Dactylaria gallopava. Treatment was initiated with amphotericin B for a
period of 21 days followed by oral itraconazole for an 8-month period.
PMID- 11008083
TI - Isoniazid prophylaxis in lung transplantation.
AB - The incidence of tuberculous disease (TD) is higher in lung-transplant patients
than in the general population. During a 7-year period, we included 61 patients
who underwent lung transplantation in a prospective isoniazid prophylaxis
protocol. Isoniazid was prescribed to infected and anergic patients not
previously treated when added to the waiting list. Six of 61 patients (10%)
developed tuberculosis. We observed no differences in tuberculous disease
incidence between infected-anergic and non-infected patients. In our tuberculous
endemic area, isoniazid prophylaxis is safe and offers protection from TD to
infected and anergic patients who must be enrolled in a lung transplantation
program.
PMID- 11008084
TI - Research and practice in adolescent medicine: "both-and" not "either-or" for
clinicians.
PMID- 11008085
TI - Social cognitions associated with pubertal development in a sample of urban, low
income, African-American and Latina girls and mothers.
AB - PURPOSE: To assess girls' acquisition of new sex-related social cognitions at
puberty and the social meanings they attribute to changes in their primary social
relationships. METHODS: As part of a larger study assessing sociosexual
cognitions of urban girls, 57 African-American and Latina mothers and 57 girls
(aged 10-13 years) participated in one of 16 focus groups. Thematic analyses were
conducted on transcripts of the mothers' and daughters' focus group sessions.
RESULTS: Analyses revealed four major themes related to pubertal development: (1)
physical maturation provides new social status of maturity; (2) puberty is
associated with changes in sexual expectations and roles; (3) girls develop
social meanings to feelings of sexual arousal; and (4) puberty prompts changes in
mother-daughter relationship control. Representative quotations are used to
illustrate each of these themes. CONCLUSIONS: Our analyses provide insight into
the ways in which late childhood and early adolescent urban girls interpret
sexuality and sexual relations, perceive changes in their social relationships,
and develop expectations regarding their roles in sexual and romantic
relationships.
PMID- 11008086
TI - Postponing sexual intercourse among urban junior high school students-a
randomized controlled evaluation.
AB - PURPOSE: To describe a randomized, controlled evaluation of a school-based
intervention to delay sexual intercourse among urban junior high school students.
METHODS: Six Washington, D.C., junior high schools were randomly assigned to the
intervention or nonintervention control condition for an educational program.
During the first school year, seventh graders (n = 582) from the six schools
obtained written parental consent to participate. Three health professionals (one
per intervention school) implemented the program, which consisted of reproductive
health classes, the Postponing Sexual Involvement Curriculum, health risk
screening, and "booster" educational activities during the following (eighth
grade) school year. Cross-sectional surveys were administered at baseline, the
end of the seventh grade, and the beginning and end of the eighth grade.
Intervention and control group differences in virginity, attitudes toward delayed
sex and childbearing, and sexual knowledge and behavior were assessed at all four
time points. RESULTS: At baseline, 44% of the seventh grade males and 81% of the
seventh grade females reported being virgins. At the end of the seventh grade
(first follow-up), after controlling for baseline study group differences,
intervention-group females were more likely to report virginity, self-efficacy to
refuse sex with a boyfriend, and the intention to avoid sexual involvement during
the following 6 months. At the end of the eighth grade, significantly more
intervention- than control-group females reported virginity, birth control use at
last intercourse (for nonvirgins), and knowledge of adolescent reproductive
health and confidentiality rights. No changes in virginity, self-efficacy to
refuse sex, or sexual intent for the next 6 months were observed among male
participants at any time during the study. However, on all three follow-up
surveys, intervention-group males scored significantly higher than their control
group counterparts in knowledge of birth control method efficacy. No change in
attitudes toward abstinence was observed for either gender at any follow-up
point. CONCLUSIONS: Gender differences in baseline sexual activity rates and in
various study outcomes suggest a possible need for separate, gender-specific
intervention activities that can adequately address the social and cognitive
needs of both sexes.
PMID- 11008087
TI - Exposure to, and perceived usefulness of, school-based tobacco prevention
programs: associations with susceptibility to smoking among adolescents.
AB - PURPOSE: To examine the relationships of exposure to school-based tobacco
prevention programs and perceived usefulness of such programs to smoking
susceptibility. METHODS: An ethnically representative sample of 6929 Grade 10
students participated in a cross-sectional survey of tobacco-related activities
and behaviors. Perceived usefulness of prevention programs was investigated
according to two dimensions: perceived helpfulness of information received at
school with regard to making decisions about tobacco use and perceived
availability of social resources that might help students cope with tobacco
related issues. RESULTS: The extent of exposure to school prevention programs and
both dimensions of perceived usefulness of these programs were inversely
associated with susceptibility to smoking. In addition, perceived information
helpfulness mediated the effect of program exposure on susceptibility status,
whereas perceived availability of social resources moderated that effect. The
study also presented evidence suggesting ethnic/cultural variability in the
status of susceptibility to smoking at this age. CONCLUSIONS: The study indicates
a need to examine the perceptions of students receiving school prevention
programs. Perceived usefulness of school prevention programs may be used to
identify youth at high risk for smoking susceptibility. Future studies, however,
should investigate other dimensions of perceived usefulness as well as
intrapersonal, interpersonal, and environmental correlates of this construct.
PMID- 11008088
TI - Psychosocial determinants of the onset and escalation of smoking: cross-sectional
and prospective findings in multiethnic middle school samples.
AB - PURPOSE: To investigate a broad range of social influence-related and global
determinants of smoking to aid in the design of comprehensive multiethnic
interventions by testing the most important factors of initiation and escalation
of smoking across various subgroups. METHODS: Cross-sectional (N = 2546) and
cohort (N = 736) samples of multiethnic middle school students near a large
Southwestern metropolis were surveyed through self-report questionnaires. The
confidential questionnaires included information on demographics, risk factors,
and smoking behavior and were administered in class by trained data collectors.
Multivariable logistic regression analysis was used to examine the statistical
significance and strength of the factors. RESULTS: Those lower in self-esteem and
higher in social assertiveness appeared to be most at risk for the onset of
smoking, whereas those low in optimism appeared to be the most at risk for the
escalation of smoking. Attitudes, friends' norms, parents' norms, perceived
behavioral control, and perceived prevalence were consistent predictors of all
smoking status outcomes. CONCLUSIONS: The behavioral-specific determinants of
smoking appear to be important predictors of smoking status outcomes in all
demographic subgroups. The relationships of the global determinants were more
dependent on the smoking outcome variable and subgroup examined. The findings may
serve to help facilitate the targeting of comprehensive interventions aimed at
reducing adolescent smoking in multiethnic and ethnic group-specific populations.
PMID- 11008089
TI - Prevalence of adolescent injury from recreational exercise: an Australian
perspective.
AB - PURPOSE: To report the prevalence of recent adolescent recreational and sporting
activities and associated injury. METHODS: Data were collected during three
school terms in 1997 using a validated questionnaire administered once only to
3538 girls and boys aged 11-12 years and 15-16 years. These students comprised
97.5% of the students in these age ranges in randomly selected state and private
schools in the Adelaide metropolitan area (South Australia). Participants
identified up to three recreational and/or sporting activities in which they had
participated in the previous week. Data were collected on the nature and extent
of participation, and on associated injuries. Participation and injury reports
were summarized descriptively in gender strata in the two adolescent age groups
and stratum specific odds ratios were used to explore injury risk. RESULTS:
Subjects reported participating in 8997 sporting and/or recreational activities
in the preceding week (an average of 2.5 participations per student). Over 140
sports and recreational pursuits were represented, incorporating organized and
nonorganized activities undertaken in teams, social groups, or alone.
Approximately 25% of adolescents reported at least one recreational injury.
Injuries were mostly minor, reflecting soft tissue trauma and skin abrasions.
Organized group sport incurred the highest risk of injury. There were marked
gender and year level differences in injury risk in a number of common
activities. CONCLUSIONS: These findings support the need for ongoing education
regarding injury prevention and management.
PMID- 11008090
TI - Reliability of adolescents' self-report of recent recreational injury.
AB - PURPOSE: To assess the reliability of adolescents' self-report of recent
recreational injury. METHOD: Identical written questionnaires were administered
twice in a 3-week period to 75 randomly selected adolescents (aged 11-12 years
and 15-16 years) in state primary and secondary schools in South Australia,
Australia. The questionnaires sought information on injury sustained in the
previous week. Parents of 60 of the adolescents were contacted in the same week
as one of the questionnaire administrations, to verify their adolescent's most
recent injury self-report. Intraclass and Pearson correlation coefficients
provided evidence of agreement between responses, and stability of measure.
RESULTS: There was high stability and good agreement between the parent and
adolescent responses provided in the same week, suggesting that adolescents
accurately reported recent recreational injury. The poor stability and low
agreement between repeated adolescent responses over the 3-week period indicated
not poor recall, but the changing nature of mostly minor recreational injury.
These findings suggest that the nature of the injury reported in the first
questionnaire had changed by the time of the second questionnaire administration,
and that this was accurately reported. CONCLUSION: Confidence can be placed in
adolescents' self-reports of recreational injury in the preceding week.
PMID- 11008091
TI - Sexual practices in Malaysia: determinants of sexual intercourse among unmarried
youths.
AB - This paper describes findings on selected determinants of sexual intercourse
among 468 unmarried adolescents from a survey in Malaysia. Data on respondents'
background, sexual experience, contraceptive use, and sexual attitudes are
provided. Based on multiple logistic regressions, factors significantly
predictive of sexual experience are gender, employment, and sexual attitudes.
PMID- 11008093
TI - Cytokine therapy in renal cell cancer.
AB - Despite extensive investigations with many different treatment modalities,
metastatic renal cell carcinoma (RCC) remains a disease highly resistant to
systemic therapy. The outlook for patients with metastatic RCC is poor, with a 5
year survival rate of less than 10%. Late relapses after nephrectomy, prolonged
stable disease in the absence of systemic therapy, and rare spontaneous
regression are clinical observations that suggest host immune mechanisms could be
important in regulating tumor growth. Interleukin-2 (IL-2) and interferon-alpha
(IFN-alpha) have been extensively studied in advanced RCC with responses in the
10 to 20% range. Two randomized trials suggest that treatment with IFN-alpha
compared with vinblastine or medroxyprogesterone results in a small improvement
in survival. Prolonged responses with high-dose IL-2 is significant but is
accompanied by formidable toxicity. Although the combination of IFN-alpha and IL
2 compared with monotherapy with IFN-alpha or IL-2 increases the response
proportion, no improvement in survival could be demonstrated in a recent
randomized trial. In addition, three randomized trials showed no survival benefit
associated with IFN-alpha therapy given as adjuvant therapy following complete
resection of locally advanced RCC. Small numbers of patients exhibit complete or
partial responses to IFN-alpha and/or IL-2, but most patients do not respond and
there are few long-term survivors. Clinical investigation of new agents and
treatment programs to identify improved antitumor activity against metastases
remain the highest priorities in this refractory disease.
PMID- 11008092
TI - Cigarette smoking in multicultural, urban high school students.
AB - PURPOSE: To profile patterns of cigarette use among a multiethnic population of
high school students, and identify important factors associated with cigarette
use by ethnicity, in order to plan effective health promotion strategies.
METHODS: This cross-sectional study involved the completion of a lifestyle
questionnaire by 1236 Grade 9-13 students (86% response rate) from 62 randomly
selected classrooms in three urban high schools in Toronto. Chi-square analysis
of the association between tobacco use and other variables took account of the
clustered sample using CSAMPLE in Epi Info. RESULTS: The students self-identified
their ethnicity as follows: 388 Canadian, 269 European, 171 East Indian, 137
Asian, 76 West Indian, and 194 "other." Students who identified themselves as
Canadians were significantly more likely to be current smokers (29%) than
students reporting other ethnicities (13%). There was no apparent increase in
smoking rates for immigrants after 2 or more years in Canada. Current drinking,
sexual activity, and especially friends smoking was most strongly associated with
current smoking for most ethnic groups, although the relative importance of these
variables was not identical for all groups. CONCLUSIONS: Prevention programs may
benefit from a focus on the influence of peer smoking and on the grouping
together of lifestyle factors associated with smoking for students in all ethnic
groups in this multicultural city.
PMID- 11008094
TI - Prostate tumor progression and prognosis. interplay of tumor and host factors.
AB - The prognosis for prostate cancer is largely dependent on the probability of
metastatic dissemination. Prognostic markers currently in use are very poor
predictors of metastatic potential, and as of yet none of the battery of new
molecular markers has proven greatly superior. This may be due in part to their
inability to assess the degree of interaction of subpopulations of prostate
cancer cells with each other and with their microenvironment. A growing body of
evidence indicates that these types of interactions are a major factor in the
eventual genesis of cancer cells capable of metastasis. Recent research has
demonstrated that specialized components of prostate tumors may play a critical
supporting role for the overall growth of the larger tumor. The multifocal nature
and apparent polyclonal origins of prostate tumors suggest that carcinogenesis
and tumor progression are promoted by global influences or "field effects." It
appears that these effects extend beyond the proliferating epithelial component
to the tissue stroma. Prostate cancer cells and stromal cells seem to act in
concert to modify the microenvironment, leading to metastasis. An understanding
of this synergy may provide a new class of prognostic markers which more
accurately measure the complex set of interactions that determine tumor behavior.
PMID- 11008095
TI - Clinical trials of immunotherapy for advanced prostate cancer.
AB - There is a lack of effective therapeutic regimens for advanced hormone-refractory
prostate cancer (HRPC). Recent combination regimens of chemotherapy have improved
management of HRPC. Neither systemic chemotherapy nor radiation regimens have
significantly improved survival. Conventional systemic cytokine therapy has had
limited efficacy in the treatment of advanced prostate cancer patients and its
toxicity is severe. Combinations of multiple biological response modifiers for
treatment of this disease also have limited efficacy. Results from phase II
trials have shown that the combination of interferon-alpha and interleukin-2
therapy and the infusion of dendritic cells primed with peptides of prostate
specific membrane antigen are promising. The former showed 31% response using the
National Prostatic Cancer Project criteria, and the latter showed 27% of
objective partial response with a reduction of >50% prostate specific antigen
level. The toxicity of these two regimens was tolerated by patients. New
approaches with tumor vaccines in conjunction with cytokine gene therapy have
also been investigated. The clinical responses of these trials have been limited
but promising. Immunotherapy may become an effective modality of prostate cancer
treatment in the future.
PMID- 11008096
TI - Comparative studies of prostate cancer in Japan versus the United States. A
review.
AB - This article reviews the available data on prostate cancer in Japan compared with
that in the United States, with emphasis on epidemiologic, pathologic, and
molecular aspects. Previous studies have demonstrated ethnic/racial differences
in the incidence of prostate cancer between the two countries. Recent
investigations indicate that different genetic alterations or polymorphisms are
related to carcinogenesis in the prostate. Comparative geographic-pathologic
autopsy studies suggest that different promoting factors including genetic,
epigenetic, and environmental influences may be responsible for ethnic variations
in the postinduction progression of prostate cancer.
PMID- 11008097
TI - Quantitative Imaging of Yttrium-86 with PET. The Occurrence and Correction of
Anomalous Apparent Activity in High Density Regions.
AB - Purpose: Yttrium-86 has been proposed for use as a quantitative positron emission
tomography imaging agent to determine the in vivo distribution of therapeutic
pharmaceuticals labeled with yttrium-90, a pure beta minus emitter. This study
identifies, and proposes a solution for, an artifact, which interferes with
quantitation.Procedures: Yttrium-86 is a 14.7-hour halflife positron emitter (33%
abundance) with multiple high energy gamma rays in cascade. Phantom measurements
with a GE Advance PET scanner using standard attenuation and scatter corrections,
demonstrated anomalous apparent activity in inactive higher density
regions.Results: Apparent activity up to 30% of the surrounding true activity was
observed in a bone equivalent material. Even higher activities were observed if
the scatter correction was omitted. This phenomenon was determined to result from
the effect of attenuation correction on true coincidences between one gamma ray
and a second gamma ray or annihilation photon.Conclusion: A simple additional
correction based on sinogram tail subtraction improves accuracy significantly.
PMID- 11008098
TI - Evaluation of Abdominal Tumors with
AB - Purpose: The purpose of this study was to evaluate the diagnostic usefulness of
fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET).Procedures:
We performed FDG-PET in 22 patients with suspected primary or recurrent cancer
(23 cases). The FDG-PET findings were compared with the final diagnosis, which
was obtained by histological examination of resected, or biopsy specimens and the
clinical course.Results: In all patients, the sensitivity, specificity, and the
accuracy of FDG-PET were 93.8%, 85.7%, 91.3%, respectively. In the patients with
colo-rectal cancer, the sensitivity, specificity, and accuracy were 92.9%, 100%,
94.4%, respectively.Conclusions: FDG-PET was considered to be clinically useful
for the detection of primary or recurrent malignant tumors, and for
differentiating recurrent tumors from inflammatory scars.
PMID- 11008099
TI - Comparison of FDG-PET and Bone Scans for Detecting Skeletal Metastases in
Patients with Non-small Cell Lung Cancer.
AB - Purpose: Positron Emission Tomography (PET) with F18-fluorodeoxyglucose has been
proven useful for staging non-small cell lung cancer. Bone scans are frequently
performed for suspected skeletal metastases. The purpose of this study was to
evaluate if bone scans compared to PET scans provide additional information that
changes the stage of disease.Procedures: Nineteen patients with non-small cell
lung cancer had PET and bone scans done for staging of the malignancy. The
results of both studies were compared.Results: Bone and PET scans agreed on the
presence or absence of skeletal metastases in all nineteen patients. The addition
of a bone scan to a PET scan did not change the stage of the disease or the
management in any of the patients. Bone scans allowed for more precise
localization of the lesions in some patients.Conclusions: Bone scans do not
change the stage of disease when performed in addition to PET scans, but provide
more precise localization of skeletal abnormalities.
PMID- 11008100
TI - Whole-Body FDG-PET in Patients with Recurrent Colorectal Carcinoma. A Comparative
Study with CT.
AB - Purpose: To assess the clinical accuracy of whole-body 2-[F-18]-fluoro-2-deoxy-D
glucose-positron emission tomography (FDG-PET) in the diagnosis of recurrent
colorectal carcinoma in comparison to conventional computed tomography
(CT).Materials and methods: Forty patients with suspected recurrent colorectal
carcinoma based on either progressive serial carcinoemrbyonic antigen (CEA) serum
elevation or positive/equivocal CT findings underwent whole-body FDG-PET. PET
results were compared with those of CT and correlated to the final
histopathological and clinical findings.Results: A final diagnosis was obtained
at 93 sites in 35 patients by histology and in 5 patients by clinical follow up
of at least 6 months. Of the 93 sites, 53 were determined to be malignant and 40
benign. FDG-PET evaluated on a 5-point scale (0-4) showed a positive and negative
predictive value in the range of 96-98% and 83-93% respectively as the threshold
for positivity was moved from 0 through 3. By comparison, CT, also evaluated on a
5-point scale showed a positive and negative predictive value in the range of 75
88% and 67-71% respectively. The area under the fitted receiver operating
characteristic curve for PET: A(PET) = 0.96 +/- 0.02 was significantly greater (P
< 0.001) than that observed for CT: A(CT) = 0.77 +/- 0.06. The distribution of
maximum standardized uptake value (SUVmax) showed that all negative lesions have
SUVmax below 5.0 whereas 75% of positive lesions were above 5.0 pointing to the
fact that disease positivity is more likely in lesions with high SUV
values.Conclusion: The results of this study confirm that whole-body FDG-PET is
more accurate than conventional CT in the staging of patients with suspected
recurrent colorectal carcinoma.
PMID- 11008101
TI - 18F-FDG Uptake in the Anterior Mediastinum. Physiologic Thymic Uptake or Disease?
AB - Purpose: We reviewed 18F-fluorodeoxyglucose (18F-FDG) studies to determine the
frequency of thymic visualization, to characterize this uptake to facilitate
differentiation from disease, and to ascertain effects of therapy on
visualization.Methods: Hybrid positron emission tomography images performed on 14
patients with known or suspected malignancy before therapy, and on six of the
patients after treatment, were reviewed. Mediastinal uptake was characterized by
location, contour and intensity.Results: Thymic uptake seen in five patients, 13
16-years-old, was characterized by an anterior midline location, regular
contours, and a mean uptake ration of 2.5, and involved large glands. In five
patients with mediastinal disease, 16-23-years-old, uptake was more posterior and
eccentric in location with irregular borders and a mean uptake ratio of 4.3. One
patient had anterior (thymic) and posterior (disease) mediastinal uptake. Three
patients, 15-22-years-old, without disease and small thymus glands had no uptake.
Five patients, including two with baseline uptake, showed no thymic uptake
subsequently. One patient, negative initially, had thymic uptake five months
after therapy.Conclusions: Thymic 18F-FDG uptake occurs in younger patients,
before or after treatment, and is associated with larger glands. Its midline
anterior mediastinal location and mild intensity should facilitate discrimination
from disease.
PMID- 11008102
TI - Occupational Exposure in Nuclear Medicine and PET.
AB - Purpose: With the increasing use of 18F-fluorodeoxyglucose (FDG) positron
emission tomography (PET) for scanning in oncology in our center, a radiation
dose survey was performed to determine the impact on staff exposure. Conventional
nuclear medicine procedures such as gallium scan, bone scans, and sestamibi
cardiac scans are used for comparative purposes.Procedure: Patients were measured
using a hand-held radiation monitor (Victoreen 450-P) at various distances and
times that replicate typical patient contact scenarios in the Diagnostic Imaging
Department.Results: We present our findings from the survey and the implications
these have on staff radiation exposure. The data suggest that emerging oncologic
techniques such as PET, high dose gallium-67, and high dose Tl-201 do not
represent a significantly greater occupational radiation hazard than conventional
nuclear medicine procedures.
PMID- 11008103
TI - Mice unresponsive to GM-CSF are unexpectedly resistant to cutaneous Leishmania
major infection.
AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to play
a protective role in leishmanial infection. Mice with a null mutation in the gene
for the beta common (beta c) chain of the receptors for GM-CSF, interleukin(IL)-3
and IL-5 (beta c-null mice) display normal steady state hemopoiesis and develop
lung disease similar to the human condition, alveolar proteinosis, due to a lack
of signaling by GM-CSF. We therefore expected to observe a heightened sensitivity
to Leishmania major in the beta c-null mice. Surprisingly, the beta c-null mice
were more resistant to cutaneous infection than wild-type (wt) mice. Upon
intradermal injection of L. major promastigotes, fewer beta c-null mice developed
cutaneous lesions than wt mice and these lesions were smaller and healed more
rapidly than in wt mice. This resistance to disease was associated with a reduced
percentage of in vitro infected beta c-null macrophages. Macrophages from beta c
null mice displayed a more activated phenotype and produced increased amounts of
nitric oxide following infection with L. major, both in vivo and in vitro.
Paradoxically, however, the parasite burden in the draining lymph nodes was
similar in both beta c-null and wt mice, suggesting that at least a subpopulation
of cells was susceptible to the parasite. The mechanism preventing normal lesion
development remains to be elucidated.
PMID- 11008104
TI - Passage of human T-cell leukemia virus type-1 during progression to cutaneous T
cell lymphoma results in myelopathic disease in an HTLV-1 infection model.
AB - Studies comparing functional differences in human T-cell leukemia virus type 1
(HTLV-1) clones that mediate distinct outcomes in experimentally infected
rabbits, resulted in a dermatopathic smoldering adult T-cell leukemia/lymphoma
following chronic infection with HTLV-1 strain RH/K34. During the 3.5 years'
follow-up, HTLV-1 skin disease progressed to cutaneous T-cell lymphoma. When
infection was passed to several naive rabbits, progressive paraparesis due to
myelopathic neurodegeneration, analogous to HTLV-associated myelopathy, resulted
in one of 4 transfusion recipients. Similar proviral loads were detected in the
two diseases, regardless of stage of progression or tissue compartment of
infection. Complete proviral sequences obtained from the donor and affected
recipient aligned identically with each other and with the inoculated virus
clone. Existence of disparate pathogenic outcomes following infectious
transmission further extends the analogy of using rabbits to model human
infection and disease. Although the experimental outcomes shown are limited by
numbers of animals affected, they mimic the infrequency of HTLV-1 disease and
authenticate epidemiological evidence of virus sequence stability regardless of
disease phenotype. The findings suggest that further investigation of a possible
role for HTLV-1 in some forms of cutaneous T-cell lymphoma is warranted.
PMID- 11008105
TI - Lipopolysaccharide-like molecules derived from Wolbachia endobacteria of the
filaria Onchocerca volvulus are candidate mediators in the sequence of
inflammatory and antiinflammatory responses of human monocytes.
AB - The majority of Onchocerca volvulus-infected persons show signs of cellular
anergy, and long-time survival of adult and larval parasites in subcutaneous
tissue is observed. The mechanisms leading to immunological hyporesponsiveness
are poorly understood. Monocytes/macrophages represent a link between the innate
and acquired immune system and are candidate cells to promote inflammatory and
antiinflammatory processes. In the present study we have shown that products of
microfilarial (O. volvulus) and adult (O. volvulus and O. ochengi) parasites
affect monocytes in vitro. An early production of TNF-alpha by exposed monocytes
was followed by the production of IL-10 and a reduced expression of HLA-DR and
the costimulatory molecules B7-1 and B7-2, while other adhesion receptors
remained unaffected. Downregulation of the functional membrane receptors failed
to occur after treatment of the cells with anti-IL-10 antibodies. The engagement
of CD14, a dominant membrane receptor on monocytes and major binding protein for
lipopolysaccharides, was indicated by partial blocking of monocyte modulation by
neutralizing antibodies to CD14 and by the antagonistic lipid A analog compound
406. Lipopolysaccharide-like molecules were detected in sterile products of O.
volvulus stages which could originate from Wolbachia bacteria related to Gram
negative Rickettsiales, known to be abundant in the hypodermis and the female
reproductive organs of O. volvulus. The present results indicate that the
monocyte/macrophage may be a major target cell for immunomodulatory parasite
derived and intraparasitic, bacteria-derived molecules, thereby contributing to
the host's cellular hyporesponsiveness.
PMID- 11008106
TI - Helicobacter pylori inhibits gastric cell cycle progression.
AB - Helicobacter pylori infection of the gastric mucosa is associated with changes in
gastric epithelial cell proliferation. In vitro studies have shown that exposure
to H. pylori inhibits proliferation of gastric cells. This study sought to
investigate the cell cycle progression of gastric epithelial cell lines in the
presence and absence of H. pylori. Unsynchronized and synchronized gastric
epithelial cell lines AGS and KatoIII were exposed to H. pylori over a 24-h
period. Cell cycle progression was determined by flow cytometry using propidium
iodide (PI), and by analysis of cyclin E, p21, and p53 protein expression using
Western blots. In the absence of H. pylori 40, 45, and 15% of unsynchronized AGS
cells were in G(0)-G(1), S, and G(2)-M phases, respectively, by flow cytometry
analysis. When AGS cells were cultured in the presence of H. pylori, the S phase
decreased 10% and the G(0)-G(1) phase increased 17% after 24 h compared with the
controls. KatoIII cells, which have a deleted p53 gene, showed little or no
response to H. pylori. When G1/S synchronized AGS cells were incubated with media
containing H. pylori, the G(1) phase increased significantly (25%, P < 0.05)
compared with controls after 24 h. In contrast, the control cells were able to
pass through S phase. The inhibitory effects of H. pylori on the cell cycle of
AGS cells were associated with a significant increase in p53 and p21 expression
after 24 h. The expression of cyclin E was downregulated in AGS cells following
exposure of AGS cells to H. pylori for 24 h. This study shows that H. pylori
induced growth inhibition in vitro is predominantly at the G(0)-G(1) checkpoint.
Our results suggest that p53 may be important in H. pylori-induced cell cycle
arrest. These results support a role for cyclin-dependent kinase inhibitors in
the G(1) cell cycle arrest exerted by H. pylori and its involvement in changing
the regulatory proteins, p53, p21, and cyclin E in the cell cycle.
PMID- 11008107
TI - Mechanisms of disposal of bacterial lipopolysaccharides by animal hosts.
AB - Much of the very extensive literature describing the (bio)chemistry and biology
of bacterial lipopolysaccharides (LPS, endotoxin) has dealt with the properties
of these molecules as potent triggers of host responses. This brief review will
focus on what has been learned recently about mechanisms by which the host can
dispose of LPS and counter its often excessive stimulatory effects.
PMID- 11008108
TI - The role of immune responses in bone loss during periodontal disease.
AB - A network of cytokines and other soluble mediators unites the immune system and
bone; bacterial infections induce immune responses which may perturb this
network. Periodontal diseases are Gram-negative infections resulting in bone loss
in the jaw. Evidence is presented that immune responses to these infections
produces net resorption of bone.
PMID- 11008109
TI - Bartonella henselae, B. quintana, and B. bacilliformis: historical pathogens of
emerging significance.
AB - Bartonella species were virtually unrecognized as modern pathogens of humans
until the last decade. However, identification of Bartonella species as the
agents of cat-scratch disease, bacillary angiomatosis, urban trench fever, and
possible novel presentations of Carrion's disease has left little doubt of the
emerging medical importance of this genus of organisms. The three primary human
pathogenic bartonellae, Bartonella bacilliformis (Carrion's disease), B. henselae
(cat-scratch disease), and B. quintana (trench fever), present noteworthy
comparisons in the epidemiology, natural history, pathology, and host-microbe
interaction that this review will briefly explore.
PMID- 11008110
TI - Helicobacter pylori motility.
AB - Motility is essential for Helicobacter pylori colonization. This review discusses
the biochemistry, genetics and genomics of the H. pylori flagellum, and compares
these features with well-characterized bacteria.
PMID- 11008111
TI - Using genetics to probe host-virus interactions; the mouse mammary tumor virus
model.
AB - It is clear that there is genetic variation among different individuals in their
susceptibility to infection by viruses and other pathogens. Identification of the
genes involved in conferring resistance or susceptibility to viral infection will
allow us to understand both mechanisms of infection and pathogenesis and to
develop reagents for treating or preventing them. Because of the large number of
genetically well-characterized inbred mouse strains and the ability to generate
targeted germ line mutations, this species is particularly well-suited for such
analysis. This review focuses on how the use of genetics to study the retrovirus
mouse mammary tumor virus allowed the dissection of both the viral infection
pathway and the response of the host to this infection.
PMID- 11008112
TI - Version 2000: the new beta-lactamases of Gram-negative bacteria at the dawn of
the new millennium.
AB - beta-lactamases of Gram-negative bacteria are evolving dynamically. New
developments include the production of enzymes with novel substrate profiles,
reduced susceptibility to beta-lactamase inhibitors, and the simultaneous
production of multiple types of beta-lactamases. The changes represent
evolutionary upgrades which provide modern pathogens with a greater potential to
resist beta-lactam antibiotics and cause formidable therapeutic, infection
control, and diagnostic challenges. This review is a clinically oriented outline
of recent developments in the beta-lactamase production of Gram-negative
bacteria.
PMID- 11008113
TI - Bacterial penetration across the blood-brain barrier during the development of
neonatal meningitis.
AB - Bacterial pathogens may breach the blood-brain barrier (BBB) and invade the
central nervous system through paracellular and/or transcellular mechanisms.
Transcellular penetration, e.g., transcytosis across the BBB has been
demonstrated for Escherichia coli K1, group B streptococcus, Listeria
monocytogenes, Citrobacter freundii and Streptococcus pneumonia strains. Genes
contributing to invasion of brain microvascular endothelial cells include E. coli
K1 genes ompA, ibeA, ibeB, and yijP. Understanding the mechanisms of bacterial
penetration across the BBB may help develop novel approaches to preventing
bacterial meningitis.
PMID- 11008114
TI - Expression and role of superoxide dismutases (SOD) in pathogenic bacteria.
AB - This review will be limited to the expression and roles of the family of
metalloenzymes superoxide dismutases in pathogenic bacteria. Only animal
pathogens will be described, with particular emphasis on those causing disease in
man.
PMID- 11008115
TI - Interleukin-18 (IL-18) and infectious diseases, with special emphasis on diseases
induced by intracellular pathogens.
AB - Interleukin-18 (IL-18) is a novel cytokine mainly produced by activated
macrophages. IL-18 was originally called interferon-gamma inducing factor, due to
its action in inducing IFN-gamma secretion from Th1 cells, NK cells and NKT
cells. It has been reported that IL-18 may play important roles in various
diseases including cancer and infectious diseases. This review deals with the
roles of IL-18 in infectious diseases, with special emphasis on IL-18 in
infectious diseases caused by intracellular pathogens including Mycobacterium
tuberculosis, Mycobacterium leprae, Listeria monocytogenes and Salmonella
typhimurium.
PMID- 11008116
TI - Overview of the epidemiology, microbiology, and pathogenesis of Leptospira spp.
in humans.
AB - Leptospirosis is probably the world's most widespread zoonosis. It remains
underdiagnosed largely due to the broad spectrum of signs and symptoms
attributable to this spirochetal pathogen. Leptospira spp. cause a diversity of
diseases from flu-like illness to Weil's syndrome with multi-organ failure.
Recent epidemics may herald a change in virulence or an alteration in the balance
between humans and their interactions with other host species and the
environment.
PMID- 11008117
TI - Structure and function of clostridial phospholipases C.
AB - A range of clostridial species produce phospholipases C. The zinc metallo
phospholipases C have related sequences but different properties. All of these
enzymes may be arranged, like alpha-toxin as two-domain proteins. Differences in
enzymatic, haemolytic and toxic properties may be explained by differences in
amino acids at key positions.
PMID- 11008118
TI - The divergent role of tumor necrosis factor receptors in infectious diseases.
AB - Tumor necrosis factor (TNF) receptor types 1 and 2 are broadly expressed by most
cell types and are activated by binding of either TNF or lymphotoxin-beta. TNF
receptor-mediated immune reactions are critically important in the pathogenesis
and control of a variety of infections caused by bacteria, viruses, protozoa, and
fungi. This review summarizes recent findings on the role of TNF receptors in
infectious diseases and discusses the divergent functions of these receptors in
immune responses.
PMID- 11008119
TI - Structure-based drug design of non-nucleoside inhibitors for wild-type and drug
resistant HIV reverse transcriptase.
AB - The generation of anti-HIV agents using structure-based drug design methods has
yielded a number of promising non-nucleoside inhibitors (NNIs) of HIV reverse
transcriptase (RT). Recent successes in identifying potent NNIs are reviewed with
an emphasis on the recent trend of utilizing a computer model of HIV RT to
identify space in the NNI binding pocket that can be exploited by carefully
chosen functional groups predicted to interact favorably with binding pocket
residues. The NNI binding pocket model was used to design potent NNIs against
both wild-type RT and drug-resistant RT mutants. Molecular modeling and score
functions were used to analyze how drug-resistant mutations would change the RT
binding pocket shape, volume, and chemical make-up, and how these changes could
affect inhibitor binding. Modeling studies revealed that for an NNI of HIV RT to
be active against RT mutants such as the especially problematic Y181C RT mutant,
the following features are required: (a) the inhibitor should be highly potent
against wild-type RT and therefore capable of tolerating a considerable activity
loss against RT mutants (i.e. a picomolar-level inhibitor against wild-type RT
may still be effective against RT mutants at nanomolar concentrations), (b) the
inhibitor should maximize the occupancy in the Wing 2 region of the NNI binding
site of RT, and (c) the inhibitor should contain functional groups that provide
favorable chemical interactions with Wing 2 residues of wild-type as well as
mutant RT. Our rationally designed NNI compounds HI-236, HI-240, HI-244, HI-253,
HI-443, and HI-445 combine these three features and outperform other anti-HIV
agents examined.
PMID- 11008120
TI - The stimulatory effects of cationic amphiphilic drugs on human platelets treated
with thrombin.
AB - The actions of eight cationic amphiphilic drugs on human platelets displayed
three different effects according to drug concentration ranges. At lower
concentrations (below approximately 25 microM), the drugs stimulated secretory
responses induced by 0.2 U/mL of thrombin, while at concentrations in the 25-50
microM range they inhibited these responses. Above 50-100 microM, the drugs
caused permeabilization of the platelet plasma membrane as measured by leakage of
cytoplasmic adenine nucleotides. The effects of these agents on phosphoinositide
metabolism were monitored in platelets prelabeled with (32)P-inorganic phosphate,
such that phosphatidic acid (PA), phosphatidylinositol 4-phosphate (PIP), and
phosphatidylinositol 4,5-bisphosphate (PIP(2)), but not phosphatidylinositol
(PI), were labeled to equilibrium. In unstimulated platelets, the level of
labeled PA decreased slightly (about 25%), with corresponding increases in PIP(2)
labeling up to drug concentrations of about 50 microM. In contrast to the
relatively small changes in PI and PIP(2), the levels of labeled PIP, precursor
to PIP(2), increased 2- to 4-fold in both resting and thrombin-treated platelets
from 5 microM up to about 50-100 microM of drugs and remained elevated throughout
the permeabilization concentrations. [(32)P]PA increased 20-fold over control
upon thrombin activation and 5-30 microM of drugs caused [(32)P]PA to increase 30
37 times over that seen in control, resting platelets; the concentration of drugs
that potentiated thrombin-induced [(32)P]PA elevation corresponded to that
causing the potentiation of platelet secretion. Higher drug concentrations
decreased [(32)P]PA elevation. [(32)P]PIP(2) levels increased about 25% in
response to thrombin treatment alone; low concentrations of drugs led to another
25% elevation. A significant decrease in [(32)P]PIP(2) was seen above 30 microM,
corresponding to inhibition of platelet secretion. Concentrations of 5-30 microM
of several psychoactive agents, both neuroleptics and antidepressants,
potentiated the thrombin-induced activation of platelets as measured by dense
granule secretion and increased turnover of phosphoinositides. Remarkably, all of
the drugs increased the levels of PIP even in resting platelets, indicating that
they have common effects apart from the specific receptor interactions currently
attributed to them. These common effects, e.g. an increase in membrane fluidity
such as is known to be caused by amphipathic agents, may be in part responsible
for the observed overlapping psychotropic effects of tricyclic antidepressants
and phenothiazines.
PMID- 11008121
TI - Differential effects of fluoxetine on murine B-cell proliferation depending on
the biochemical pathways triggered by distinct mitogens.
AB - The effect of fluoxetine on mitogen-induced B-cell proliferation was studied. In
particular, we analyzed the influence of fluoxetine on the signal transduction
pathways triggered after stimulation with lipopolysaccharide (LPS) and anti
immunoglobulin M antibodies (anti-IgM). We showed that fluoxetine had a dual
effect on anti-IgM-stimulated B-cell proliferation: at optimal anti-IgM
concentration, fluoxetine inhibited proliferation, whereas at suboptimal anti-IgM
concentration, the drug enhanced proliferation. Fluoxetine exerted only an
inhibitory effect on LPS-induced B-cell proliferation. Calcium influx seemed to
be involved in these effects.
PMID- 11008122
TI - Profiles of antioxidant/electrophile response element (ARE/EpRE) nuclear protein
binding and c-Ha-ras transactivation in vascular smooth muscle cells treated with
oxidative metabolites of benzo[a]pyrene.
AB - Activation of nuclear protein binding to the antioxidant/electrophile response
element (ARE/EpRE) by benzo[a]pyrene (BaP) in vascular smooth muscle cells
(vSMCs) is associated with transcriptional deregulation of c-Ha-ras. This
response may be mediated by oxidative intermediates of BaP generated during the
course of cellular metabolism. To test this hypothesis, the profile of ARE/EpRE
protein binding and transactivation elicited by BaP was compared with that of 3
hydroxy BaP (3-OH BaP) (0.03 to 3.0 microM), BaP 7,8-dihydrodiol (BaP 7,8-diol)
(0.03 to 3.0 microM), BaP 3,6-quinone (BaP 3,6-Q) (0.0003 to 3.0 microM), and
H(2)O(2) (25 to 100 microM). Specific protein binding to the consensus c-Ha-ras
ARE/EpRE was observed in vSMCs treated with all BaP metabolites at concentrations
considerably lower than those required for the parent compound. H(2)O(2), a by
product of BaP 3,6-Q redox cycling, also increased binding to the ARE/EpRE.
Treatment of vSMCs with oxidative BaP metabolites or H(2)O(2) transactivated the
c-Ha-ras promoter in all instances, but the response was consistently half of the
maximal induction elicited by BaP. Similar proteins cross-linked specifically to
the consensus c-Ha-ras ARE/EpRE sequence in cells treated with BaP or its
oxidative intermediates. The protein binding profile in the c-Ha-ras promoter was
similar to that in the NADPH:quinone reductase gene (NQO(1)) and the glutathione
S-transferase Ya gene (GSTYa) promoters, but the relative abundance of individual
complexes was promoter-specific. We conclude that oxidative intermediates of BaP
mediate activation of nuclear protein binding to ARE/EpRE and contribute to
transcriptional de-regulation of c-Ha-ras in vSMCs.
PMID- 11008123
TI - Peroxide-like oxidant response in lungs of newborn guinea pigs following the
parenteral infusion of a multivitamin preparation.
AB - The multivitamin solution is a major component responsible for the photo-induced
generation of peroxides in parenteral nutrition. The lung is a target of oxidant
injury; however, the specific role of infused peroxides is unknown. The aim of
this study was to determine if parenteral multivitamins induce in the lung an
oxidant challenge similar to that of peroxides. Newborn guinea pigs were infused
with dextrose plus relevant concentrations of H(2)O(2) (0,250,500 microM) or
multivitamins (0,1%), as well as parenteral nutrition supplemented with
multivitamins (0,1%). After 4 days, total glutathione, glutathione-related
enzymes, and oxidant-sensitive eicosanoids were measured in the lungs. Peroxides
as well as multivitamins led to a significant decrease in glutathione and the
activity of glutathione synthase, indicating that infused peroxides were not
entirely transformed into free radicals, which would have stimulated glutathione
synthesis. The multivitamin solution induced a response in oxidant-sensitive
eicosanoids similar to the response to peroxides, suggesting an oxidant stress
that was not alleviated by the antiradical properties of its components. The
effects on prostaglandins occurred independently from the stimulation in
glutathione levels induced by parenteral nutrition. The multivitamin solution
carries an oxidant load and causes effects similar to those of peroxides in the
lungs of newborn guinea pigs.
PMID- 11008124
TI - Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells:
role of ERCC1-XPF.
AB - Increased platinum-DNA adduct removal has been shown by several DNA repair assays
to be associated with cisplatin resistance in the A2780/C-series human ovarian
cancer model system. In the present study, we provide further evidence that the
resistance phenotype of these cell lines is due, in part, to enhanced nucleotide
excision repair (NER). Cisplatin resistance was found to be associated with
increased UV resistance. Northern blot analysis revealed that increased
expression of ERCC1 was also associated with cisplatin resistance in this panel.
Several other NER genes were found to be constitutively overexpressed in the most
resistant cell line, C200, as compared with the parental A2780 cells. A plasmid
substrate containing a site-specific cisplatin adduct was used to measure the
nucleotide excision activity of cell extracts prepared from cisplatin-sensitive
and -resistant cells. Using this in vitro assay, extracts prepared from C200
cells exhibited approximately 3-fold more activity than extracts prepared from
A2780 cells, similar to the difference in UV sensitivity. Complementation of
A2780 extracts with ERCC1-XPF protein resulted in approximately 2-fold increased
activity, but had little effect on excision in C200 extracts. Overall, these
results support a role for the ERCC1-XPF endonuclease as a determinant of
increased NER in this cisplatin resistance model.
PMID- 11008125
TI - Inverse agonist properties of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4
dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR141716A) and 1-(2
chlorophenyl)-4-cyano-5-(4-methoxyphenyl)-1H-pyrazole-3-carboxyl ic acid
phenylamide (CP-272871) for the CB(1) cannabinoid receptor.
AB - Two subtypes of cannabinoid receptors are currently recognized, CB(1), found in
brain and neuronal cells, and CB(2), found in spleen and immune cells. We have
characterized 1-(2-chlorophenyl)-4-cyano-5-(4-methoxyphenyl)-1H-pyrazole-3
carboxyl ic acid phenylamide (CP-272871) as a novel aryl pyrazole antagonist for
the CB(1) receptor. CP-272871 competed for binding of the cannabinoid agonist
(3)H-labeled (-)-3-[2-hydroxy-4-(1, 1-dimethylheptyl)-phenyl]-4-[3
hydroxypropyl]cyclohexan-1-ol ([(3)H]CP-55940) at the CB(1) receptor in rat brain
membranes with a K(d) value 20-fold greater than that of N-(piperidin-1-yl)-5-(4
chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl
(SR141716A). CP-272871 also competed for binding with the aminoalkylindole
agonist (3)H-labeled (R)-(+)-[2, 3-dihydro-5-methyl-3-[(4
morpholinyl)methyl]pyrrolo[1,2,3-de]1, 4-benzoxazin-6-yl](1-naphthyl)methanone
([(3)H]WIN-55212-2), as well as the aryl pyrazole antagonist [(3)H]SR141716A.
Inverse agonist as well as antagonist properties were observed for both SR141716A
and CP-272871 in signal transduction assays in biological preparations in which
the CB(1) receptor is endogenously expressed. SR141716A augmented secretin
stimulated cyclic AMP (cAMP) accumulation in intact N18TG2 neuroblastoma cells,
and this response was reversed by the agonist desacetyllevonantradol. CP-272871
antagonized desacetyllevonantradol-mediated inhibition of adenylyl cyclase in
N18TG2 membranes, and increased adenylyl cyclase activity in the absence of
agonist. SR141716A and CP-272871 antagonized desacetyllevonantradol-stimulated
(35)S-labeled guanosine-5'-O-(gamma-thio)-triphosphate ([(35)S]GTPgammaS) binding
to brain membrane G-proteins, and decreased basal [(35)S]GTPgammaS binding to G
proteins. K(+) enhanced CP-272871 and SR141716A inverse agonist activity compared
with Na(+) or NMDG(+) in the assay. These results demonstrated that the aryl
pyrazoles SR141716A and CP-272871 behave as antagonists and as inverse agonists
in G-protein-mediated signal transduction in preparations of endogenously
expressed CB(1) receptors.
PMID- 11008126
TI - CYP3A-inducing agents and the attenuation of uroporphyrin accumulation and
excretion in a rat model of porphyria cutanea tarda.
AB - An experimental model of porphyria cutanea tarda (PCT) can be achieved in 3 weeks
by a single injection of a mixture of polychlorinated biphenyls (Aroclor 1254)
into iron-loaded female Fischer 344 rats maintained continuously on delta
aminolevulinic acid-supplemented drinking water. In this model, daily treatment
with 5-pregnen-3 beta-ol-20-one-16 alpha-carbonitrile (pregnenolone 16 alpha
carbonitrile) attenuated uroporphyrin and heptacarboxylporphyrin accumulation and
excretion by 75%. Pregnenolone 16 alpha-carbonitrile treatment had only a minor
effect on hepatic iron stores, and it had no effect on the induction of CYP1A
activities by Aroclor 1254. In the absence of Aroclor 1254, pregnenolone 16 alpha
carbonitrile had no effect on the accumulation and excretion of highly
carboxylated porphyrins. Attenuation of porphyrin accumulation could also be
demonstrated with daily troleandomycin treatment. Troleandomycin increased CYP3A
dependent erythromycin demethylase activity, but to a lesser extent than
pregnenolone 16 alpha-carbonitrile. Much of the CYP3A induced by troleandomycin
was sequestered as a catalytically inactive metabolic-intermediate complex. In
the absence of Aroclor 1254, troleandomycin had no effect on the accumulation and
excretion of highly carboxylated porphyrins, nor did troleandomycin alter the
induction of CYP1A by Aroclor 1254. The results suggest that the major
attenuation of hepatic accumulation and urinary excretion of uro- and
heptacarboxylporphyrins in the rat PCT model by pregnenolone 16 alpha
carbonitrile and troleandomycin is due to an enhancement of CYP3A catalytic
activity.
PMID- 11008127
TI - Characterization and effects of methyl-2- (4-aminophenyl)-1, 2-dihydro-1-oxo-7-
(2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate
sulfate (T-1032), a novel potent inhibitor of cGMP-binding cGMP-specific
phosphodiesterase (PDE5).
AB - An isoquinolone derivative, methyl-2-(4-aminophenyl)-1, 2-dihydro-1-oxo-7-(2
pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate
(T-1032), was found to be a novel potent inhibitor of cyclic GMP (cGMP)-binding
cGMP-specific phosphodiesterase (PDE5). We investigated the inhibitory effects of
T-1032 on six PDE isozymes isolated from canine tissues. T-1032 specifically
inhibited the hydrolysis of cGMP by PDE5 partially purified from canine lung, at
a low concentration (IC(50) = 1.0 nM, K(i) = 1.2 nM), in a competitive manner. In
contrast, the IC(50) values of T-1032 for PDE1, PDE2, PDE3, and PDE4 were more
than 1 microM. T-1032 also inhibited PDE6 from canine retina with an IC(50) of 28
nM, which is of the same order of magnitude as the IC(50) of sildenafil. cGMP
hydrolytic activities of two alternative splice variants of canine PDE5 expressed
in COS-7 cells were inhibited by this compound to a similar extent. T-1032
increased the intracellular concentration of cGMP in cultured rat vascular smooth
muscle cells in the presence and absence of C-type natriuretic peptide, an
activator of membrane-bound guanylate cyclase, whereas the compound did not
change cyclic AMP levels. These data indicated that T-1032, which belongs to a
new structural class of PDE5 inhibitors, is a potent and selective PDE5
inhibitor. This compound may be useful in pharmacological studies to examine the
role of a cGMP/PDE5 pathway in tissues.
PMID- 11008128
TI - Prevention of cisplatin-DNA adduct repair and potentiation of cisplatin-induced
apoptosis in ovarian carcinoma cells by proteasome inhibitors.
AB - Histones H2A and H2B are known to be reversibly post-translationally modified by
ubiquitination. We previously observed in cultured tumor cells that proteasome
inhibition stabilizes polyubiquitinated proteins, depletes unconjugated
ubiquitin, and thereby promotes the deubiquitination of nucleosomal histones in
chromatin. Provocative indirect evidence suggests that histone
ubiquitination/deubiquitination cycles alter chromatin structure, which may limit
accessibility of DNA repair proteins to damaged sites. In the present study, we
focused on the relationship between the ubiquitination status of histone H2A, the
structure of chromatin, and the efficiency of nucleotide excision repair (NER) of
cisplatin-DNA adducts in human ovarian carcinoma cells exposed to the antitumor
drug cisplatin. Pretreating cells with the proteasome inhibitor lactacystin (LC)
or N-acetyl-leucyl-leucyl-norleucinal (ALLnL) induced deubiquitination of
ubiquitinated histone H2A (uH2A) and concomitantly promoted chromatin
condensation, increased the extent of cisplatin-DNA adducts, and diminished NER
dependent repair of cisplatin-DNA lesions, compared with control cells treated
with cisplatin alone. Both proteasome inhibitors also prevented the increase in
ERCC-1 mRNA expression that occurs in cells exposed to cisplatin. Cells treated
with the combination of ALLnL and cisplatin underwent apoptosis, as indicated by
caspase-dependent poly(ADP-ribose) polymerase (PARP) cleavage, more quickly than
cells treated with either agent alone. Additionally, the combination of ALLnL and
cisplatin potently increased p53 levels in cell lysates and stimulated the
binding of p53 to chromatin. Together, these observations suggest that proteasome
inhibition may be exploited therapeutically for its potential to sensitize
ovarian tumor cells to cisplatin.
PMID- 11008129
TI - Effects of resveratrol on the autophosphorylation of phorbol ester-responsive
protein kinases: inhibition of protein kinase D but not protein kinase C isozyme
autophosphorylation.
AB - The natural product resveratrol is a potent antagonist of phorbol ester-mediated
tumor promotion and in vitro cellular responses to phorbol-ester tumor promoters,
but it is only weakly inhibitory against the phosphorylation of conventional
exogenous substrates by phorbol ester-responsive protein kinase C (PKC) isozymes.
In this report, we compare the effects of resveratrol against the
autophosphorylation reactions of PKC isozymes versus the novel phorbol ester
responsive kinase, protein kinase D (PKD). We found that resveratrol inhibits PKD
autophosphorylation in a concentration-dependent manner, but has only negligible
effects against the autophosphorylation reactions of representative members of
each PKC isozyme subfamily (cPKC-alpha, -beta(1), and -gamma, nPKC-delta and
epsilon, and aPKC-zeta). Resveratrol was comparably effective against PKD
autophosphorylation (IC(50) = 52 microM) and PKD phosphorylation of the exogenous
substrate syntide-2 (IC(50) = 36 microM). The inhibitory potency of resveratrol
against PKD is in line with the potency of resveratrol observed in cellular
systems and with its potency against other purified enzymes and binding proteins
that are implicated in the cancer chemopreventive activity of the polyphenol.
Thus, PKD inhibition may contribute to the cancer chemopreventive action of
resveratrol.
PMID- 11008130
TI - Correlation of a unique 220-kDa protein with vitamin D sensitivity in glioma
cells.
AB - We have investigated the antitumor and apoptotic effects of 1, 25
dihydroxyvitamin D(3) (VD(3)) in glioma cell lines and in primary cultures
derived from surgical specimens from patients. Our results showed that certain
glioma cells underwent apoptosis, whereas others were resistant. In an attempt to
search for parameters that dictate VD(3) sensitivity, we discovered a unique 220
kDa protein in glioma cells that were sensitive to VD(3). This protein was not a
classical vitamin D receptor (VDR), but was recognized by two different anti-VDR
monoclonal antibodies. Furthermore, the level of the 220-kDa protein was
inversely correlated with the IC(50) of VD(3) in these glioma cells. This 220-kDa
protein was also present in frozen brain tumor samples, and the level of
expression appeared to correlate with their corresponding primary cultures. Thus,
our findings suggest that this 220-kDa protein may play an important role in
determining VD(3) sensitivity in malignant glioma.
PMID- 11008131
TI - Novel mechanisms of DNA topoisomerase II inhibition by pyranonaphthoquinone
derivatives-eleutherin, alpha lapachone, and beta lapachone.
AB - Pyranonaphthoquinones have diverse biological activities against Gram-positive
bacteria, fungi, and mycoplasms, and, recently, there has also been an increasing
interest in their anti-cancer activity. This study includes three derivatives:
eleutherin (compound 1), beta lapachone (compound 2), and its structural isomer,
alpha lapachone (compound 3). The mechanism of topoisomerase II inhibition by the
three derivatives was examined systematically with respect to the steps of the
catalytic cycle of the enzyme. Etoposide, the prototypical enzyme poison, was
used as a control and in combination with compounds 1-3 to localize their
mechanism of action. The study revealed that eleutherin (1) and beta lapachone
(2) inhibited topoisomerase II by inducing religation and dissociation of the
enzyme from DNA in the presence of ATP. Whereas compound 2 was an "irreversible"
inhibitor of topoisomerase II, compound 1 merely slowed the catalytic cycle of
the enzyme. alpha Lapachone (3), on the other hand, inhibited initial non
covalent binding of topoisomerase II to DNA and, in addition, induced religation
of DNA breaks (even in pre-established ternary complexes) before dissociating the
enzyme from DNA. Compound 3 was an "irreversible" inhibitor of topoisomerase II.
The diverse and unique mechanisms of topoisomerase II inhibition by
pyranonaphthoquinone derivatives reveal novel ways to target the enzyme with
potential for anti-cancer drug design.
PMID- 11008132
TI - Phospholipids as multidrug resistance modulators of the transport of epirubicin
in human intestinal epithelial Caco-2 cell layers and everted gut sacs of rats.
AB - Phospholipids have been increasingly used as carriers for the delivery of a
variety of drugs. Studies using cancer chemotherapeutic agents such as epirubicin
encapsulated in liposomes, which are made of phospholipids and other ingredients,
have generally shown reduced toxicity and enhanced therapeutic efficacy. The
recent investigation of the role of P-glycoprotein (P-gp) in phospholipid
translocation has opened a new area of research on the possible use of
phospholipids as multidrug resistance (MDR) modulators. This study investigated
the effects of liposomal encapsulation, empty liposome pretreatment, or free
lipid pretreatment on the uptake and transport of epirubicin in the human colon
adenocarcinoma cell line Caco-2 and in everted gut sacs of rat jejunum and ileum.
Epirubicin uptake experiments, using a flow cytometer, showed that both liposomal
encapsulation and empty liposome pretreatment increased the intracellular
accumulation of epirubicin in Caco-2 cells significantly. These two treatments
substantially increased apical-to-basolateral absorption of epirubicin across
Caco-2 monolayers and markedly improved mucosal-to-serosal absorption of
epirubicin in rat jejunum and ileum. Enhancement also was observed with both
liposome encapsulation and empty liposome pretreatment in the reduction of
basolateral-to-apical efflux of epirubicin across Caco-2 monolayers. However,
because diffusion of free dipalmitoyl phosphatidylcholine (DPPC) or dipalmitoyl
phosphatidylethanolamine (DPPE) lipids across the cell membrane is very slow,
these free lipids showed marginal effects on absorption and/or secretion of
epirubicin in both Caco-2 cells and rat gut sacs. The study suggests that
inhibition of P-gp or other transporter proteins located in the intestines may be
partially involved in the reduction of epirubicin efflux. In conclusion, the
therapeutic efficacy of epirubicin may be improved by using phospholipids as
excipients and MDR modulators in the formulations. Liposomal formulations may
have important applications to circumvent drug resistance in cancer chemotherapy.
PMID- 11008133
TI - Promitogenic effects of ethanol, methanol, and ethanolamine in insulin-treated
fibroblasts.
AB - The zinc-dependent potentiating effect of ethanol (EtOH) on insulin-stimulated
DNA synthesis was studied with a focus on the possible site of EtOH action and
the ability of other alcohols to elicit similar promitogenic effects. In serum
starved (27 hr) NIH 3T3 fibroblasts, 200-300 mM methanol (MeOH) and 0.1-1.5 mM
ethanolamine (Etn), but not 3- to 9-carbon normal alcohols, enhanced the effect
of insulin on DNA synthesis to varying extents. The promitogenic effects of EtOH
and MeOH, but not that of Etn, required the presence of 15-25 microM zinc. The
potentiating effects of Etn were enhanced by 5 mM choline (Cho) and inhibited by
1-3 mM hemicholinium-3 (HC-3), an inhibitor of Cho transporter and Cho kinase. In
the presence of 15 microM zinc, 40 mM EtOH, which had no effect on its own,
inhibited the potentiating effects of Cho and enhanced the inhibitory effects of
HC-3 on synergistic stimulation of DNA synthesis by Etn and insulin. On the other
hand, both Cho and HC-3 partially inhibited the promitogenic effect of 80 mM EtOH
in the presence of 25 microM zinc. After a 10-min incubation, EtOH decreased the
amount of cell-associated [(14)C]Cho in the absence but not in the presence of HC
3. After a 40-min incubation, Cho (5 mM) partially inhibited the cellular uptake
as well as the metabolism of [(14)C]Etn. Whereas after the 40-min incubation 80
mM EtOH had no effects on Etn metabolism, in the absence of Cho it decreased the
amount of cell-associated [(14)C]Etn. However, EtOH had no detectable effects on
cell association of [(14)C]Etn after the 10-min incubation. The results suggest
that in NIH 3T3 fibroblasts EtOH is a remarkably specific promitogen, and that it
may act via a cell membrane site(s), also regulated by Cho (agonist) and HC-3
(antagonist), which can influence membrane binding and the promitogenic activity
of Etn.
PMID- 11008135
TI - What limits simultaneous discrimination accuracy?
AB - Discrimination accuracy decreases when viewers simultaneously monitor two
perceptually distinct stimulus components for changes in a common property, e.g.
contrast [Magnussen & Greenlee (1997). Journal of Experimental Psychology: Human
Perception and Performance, 23, 1603-1616; Olzak & Wickens (1997). Perception,
26, 1101-1120]. We ask whether the limitation is in monitoring two components or
in making dual decisions about a single property. Using the same uncertainty
paradigm as Magnussen and Greenlee, we find no evidence of a processing
limitation when viewers simultaneously monitor one component (1.25 c/d) for a
possible change in contrast and a second component (5 c/d) for a possible change
in spatial frequency, regardless of whether the components are spatially
separated or superimposed. The limitation is in making dual decisions about a
single property.
PMID- 11008134
TI - Inhibition of agonist-induced p42 and p38 mitogen-activated protein kinase
phosphorylation and CD40 ligand/P-selectin expression by cyclic nucleotide
regulated pathways in human platelets.
AB - Platelet activation and adhesion to endothelial cells and extracellular matrix
proteins are crucial events in the development of arterial cardiovascular
diseases. Platelet activation is initiated by stimulation of intracellular
signaling cascades, including the p42 mitogen-activated protein kinase (MAPK) and
p38 MAPK pathways, followed by major changes in the platelet cytoskeleton and
expression and activation of platelet surface receptors, such as P-selectin
(CD62P) and CD40 ligand (CD40L). Activated platelets directly bind to vascular
endothelial cells via CD40L/CD40 interactions and induce inflammatory reactions
that initiate or aggravate atherosclerotic lesions. The aim of this study was to
investigate effects of two known platelet inhibitors-the cAMP-elevating
prostaglandin E(1) (PG-E(1)) and the cGMP-elevating sodium nitroprusside (SNP)-on
platelet p42 MAPK and p38 MAPK activation as well as on surface expression of
CD62P and CD40L. MAPK activation was analyzed by Western blot experiments using
phosphorylation-specific antibodies, and surface CD40L and CD62P expression was
determined by flow cytometry analysis. PG-E(1) and SNP strongly inhibited p42 and
p38 MAPK phosphorylation as well as CD40L and CD62P expression in response to
thrombin, a thromboxane A(2) analog, and ADP. These data indicate that adenosine
and guanosine 3',5'-cyclic monophosphate-dependent protein kinases not only
inhibit platelet pathways leading to activation and aggregation, but also those
resulting in enhanced surface expression of protein ligands involved in
inflammation. Expression of CD40L and CD62P was found to be independent of MAPK
activation, since it was not inhibited by specific MAPK inhibitors. Inhibition of
platelet-induced inflammatory responses including CD62P- and CD40L-mediated
interaction of platelets with leukocytes and endothelial cells, respectively, is
suggested to be an important component of the long-term vasoprotective effects of
cyclic nucleotide-elevating prostaglandins and NO donors.
PMID- 11008136
TI - A central mechanism of chromatic contrast.
AB - The color appearance of a light can be altered by introducing a second,
surrounding field. This phenomenon, called chromatic induction, is attenuated by
chromatic variation within a remote region outside the surround [Shevell & Wei
(1998). Vision Research, 38, 1561-1566]. We now consider the locus of the neural
mechanism mediating the attenuation caused by the remote chromatic contrast. In
the first experiment, the magnitude of chromatic variation within the remote
region is changed either: (i) in the same eye that views the patch judged in
color; or (ii) in only the opposite eye. The measurements are virtually the same
in both cases, which implies attenuation of chromatic induction is mediated by a
central, binocular mechanism. In the second experiment, the patch with its
immediate inducing surround is changed in binocular disparity relative to the
remote region with chromatic variation. The patch and surround, seen together in
one depth plane, are perceived to be in front of, behind, or in the same plane as
the remote region with chromatic variation. Attenuation of chromatic induction is
strongest when the patch and surround are in the same depth plane as the remote
region. This change of color appearance with disparity is consistent with a
central binocular process. Overall, the color-appearance measurements are
explained by monocular encoding of chromatic differences at edges, and a central
binocular mechanism of chromatic-contrast gain control.
PMID- 11008137
TI - Salience from feature contrast: variations with texture density.
AB - The salience of popout targets was measured in regular line arrays as a function
of texture density. Test targets (singletons with orientation, motion, or
luminance contrast) presented at different raster widths were compared with
reference lines (lines brighter than surrounding lines) presented at fixed raster
width. The luminance at which the reference target appeared as salient as the
particular test target was taken as a measure of the relative salience of the
test target. For orientation or motion contrast, targets at medium to small
raster widths were far more salient than targets in sparse or very dense line
arrangements. For targets defined by luminance contrast, salience variations with
texture density were less pronounced. Some subjects also reported salience for
lines in sparse arrangements even when these did not display feature contrast.
When such non-specific saliency effects were subtracted from the actual
measurements, salience curves for orientation or motion contrast revealed peaks
of increased sensitivity at line spacings below 2-3 deg and flat curves at larger
grid sizes. In an additional experiment, saliency effects from orientation
contrast were measured using texture lines of different size. Salience variations
were commonly observed. However, the curves were not found to scale with the
different sizes of texture elements but were constantly related to the free space
between neighbouring lines. This suggests that peaks in the salience profiles
reflect the limited spatial extent of the underlying neural mechanisms.
PMID- 11008138
TI - Exposure duration affects the perceived direction of cyclopean type II plaids.
AB - This study investigated the effect of exposure duration on the perceived
direction of cyclopean Type I and Type II plaids moving in the X/Y plane. The
cyclopean plaids were created from grating components defined by binocular
disparity embedded in a dynamic random-dot stereogram. The results showed that
the cyclopean Type I plaid appeared to move in the intersection-of-constraints
(IOC) direction across the range of exposures tested. However, the cyclopean Type
II plaids appeared to move in a direction different from the IOC with short
exposures but near the IOC with long exposures. This perceived directional shift
was also obtained with luminance-defined Type II plaids. A common pattern-motion
mechanism that processes cyclopean and luminance motion signals appears
responsible for the perceived directional shift of the Type II plaids.
PMID- 11008139
TI - Perceptual learning for a pattern discrimination task.
AB - Our goal was to differentiate low and mid level perceptual learning. We used a
complex grating discrimination task that required observers to combine
information across wide ranges of spatial frequency and orientation. Stimuli were
'wicker'-like textures containing two orthogonal signal components of 3 and 9
c/deg. Observers discriminated a 15% spatial frequency shift in these components.
Stimuli also contained four noise components, separated from the signal
components by at least 45 degrees of orientation or approximately 2 octaves in
spatial frequency. In Experiment 1 naive observers were trained for eight
sessions with a four-alternative same-different forced choice judgment with
feedback. Observers showed significant learning, thresholds dropped to
approximately 1/3 of their original value. In Experiment 2 we found that
observers showed far less learning when the noise components were not present.
Experiment 3 found, unlike many other studies, almost complete transfer of
learning across orientation. The results of Experiments 2 and 3 suggest that,
unlike many other perceptual learning studies, most learning in Experiment 1
occurs at mid to high levels of processing rather than within low level analyzers
tuned for spatial frequency and orientation. Experiment 4 found that performance
was more severely impaired by spatial frequency shifts in noise components of the
same spatial frequency or orientation as the signal components (though there was
significant variability between observers). This suggests that after training
observers based their responses on mechanisms tuned for selective regions of
Fourier space. Experiment 5 examined transfer of learning from a same-sign task
(the two signal components both increased/decreased in spatial frequency) to an
opposite-sign task (signal components shifted in opposite directions in frequency
space). Transfer of learning from same-sign to opposite-sign tasks and vice versa
was complete suggesting that observers combined information from the two signal
components independently.
PMID- 11008140
TI - Spatial color contrast matching: broad-bandpass functions and the flattening
effect.
AB - The contrast matching function (CMF) is the reciprocal of test contrast that
perceptually matches the contrast of standard pattern, measured as a function of
test spatial frequency (SF). Achromatic CMFs usually flatten as the contrast of
the standard is raised, and are broader than the achromatic, bandpass, contrast
sensitivity function (CSF). This report investigates whether chromatic CMFs have
similar characteristics. For this purpose, the red-green color channel was
defined using minimum flicker and hue cancellation techniques. Spatially
localized (D6), vertical, equiluminant patterns (SFs: 0.063-8 cpd; contrast: 3
80%) were used to measure the CSF and CMF of isoluminant patterns presented with
a temporal Gaussian envelope. CMFs were measured using a randomized double
staircase procedure and the two-interval forced choice technique. Two color
normal observers, whose task was to select the interval that had higher color
contrast, participated in experiments. Results show that: (a) the color CMFs are
lowpass functions of SF at low standard contrasts (3-12.5%), broad-bandpass at
intermediate contrasts (6.25-60%), and near-flat at high contrasts (80%); and (b)
isoluminant CMFs have higher upper cut-off frequencies than isoluminant CSFs. It
is concluded that: (i) color-contrast-constancy (CMF independent of SF) is partly
achieved at high contrasts because color CMFs flatten as contrast increases; (ii)
the information processing at suprathreshold levels is different from that at the
threshold levels; and (iii) the model that explained achromatic CMFs using
achromatic threshold mechanisms could not explain chromatic CMFs using chromatic
threshold mechanisms.
PMID- 11008141
TI - Relative contributions of sustained and transient pathways to human
stereoprocessing.
AB - It has been proposed [Hubel & Livingstone (1987) Journal of Neuroscience, 7, 3378
3415] that stereopsis is mediated solely by magnocellular pathway in primates.
This hypothesis was evaluated for humans in psychophysical experiments with
dynamic random-noise stimuli, based on the sustained/transient relationship of
behavior mediated by the two divisions of the LGN [Merigan & Maunsell (1993)
Annual Review of Neuroscience, 16, 369-402]. The stereoscopic limits show that
stereoscopic system is more sensitive to sustained random-dot stimuli than to
transient ones. Quantitative modeling of the result implied a weak role for
magnocellular input, suggests that human stereopsis is more strongly influenced
by parvocellular input through the LGN.
PMID- 11008142
TI - Spectral tuning of dichromats to natural scenes.
AB - Multispectral images of natural scenes were collected from both forests and coral
reefs. We varied the wavelength position of receptors in hypothetical dichromatic
visual systems and, for each receptor pair estimated the percentage of
discriminable points in natural scenes. The optimal spectral tuning predicted by
this model results in photoreceptor pairs very like those of forest dwelling,
dichromatic mammals and of coral reef fishes. Variations of the natural
illuminants in forests have little or no effect on optimal spectral tuning, but
variations of depth in coral reefs have moderate effects on the spectral
placement of S and L cones. The ratio of S and L cones typically found in
dichromatic mammals reduces the discriminability of forest scenes; in contrast,
the typical ratio of S and L cones in coral reef fishes achieves nearly the
optimal discrimination in coral reef scenes.
PMID- 11008143
TI - Optical correction of form deprivation myopia inhibits refractive recovery in
chick eyes with intact or sectioned optic nerves.
AB - The finding that the eyes of young chicks recover quickly from form deprivation
myopia (FDM) has been interpreted as indirect evidence for active
emmetropization. More direct evidence would be the demonstration that correction
of FDM with spectacle lenses, thereby removing the defocus signal, prevents
recovery. We investigated this issue in eyes with intact and sectioned (ONS)
optic nerves. Previous studies suggest that an intact optic nerve is necessary
for accurate emmetropization. Seventy day-old male chicks were monocularly
deprived using velcro-mounted diffusers, which were removed after 5-6 days and in
some (n=51), but not all cases, replaced by spectacle lenses (-5, -10 or -15 D).
Approximately half (n=34) of the chicks also underwent ONS on day 1. Refractive
errors and axial ocular dimensions were measured when the diffusers were first
removed and thereafter at 2-4 day intervals over the following 1-2 weeks. In one
case, measurements were continued at less regular intervals to 33 days. Lens
powers were selected to either approximately correct or under-correct the
refractive errors present when the diffusers were removed. Form deprivation in
normal chicks produced large myopic shifts in refraction (means for groups range
from -9.20 to -16.07 D). When the deprivation treatment was terminated, the
myopia quickly decreased to negligible levels unless optically corrected.
Correcting lenses stabilized the myopia to a level consistent with the lens power
used. Interocular differences in axial length were consistent with an axial
origin to the refractive changes. Results for the ONS groups exhibited similar
trends although there was increased variability in the data. The findings support
the interpretation that recovery from FDM is a product of active emmetropization.
That ONS increased the variability of such responses implies that an intact optic
nerve is required for accurate emmetropization.
PMID- 11008144
TI - Influence of monocular deprivation during infancy on the later development of
spatial and temporal vision.
AB - Using the method of limits, we measured spatial and temporal vision in 15
patients, aged 4-28 years, who had been monocularly deprived of patterned visual
input during infancy by a dense cataract. All patients showed losses in both
spatial and temporal vision, with greater losses in spatial than in temporal
vision. Losses were smaller when there had been more patching of the non-deprived
eye. The results indicate that visual deprivation has smaller effects on the
neural mechanisms mediating temporal vision than on those mediating spatial
vision.
PMID- 11008146
TI - In this issue
PMID- 11008145
TI - Amblyopic deficits in detecting a dotted line in noise.
AB - We compared detectability of a dotted line masked by random-dot noise for the
amblyopic versus non-amblyopic eye of two strabismic amblyopes. Small but
consistent deficits in the amblyopic eye of these observers were found, and shown
to be limited to dotted-line targets composed of greater than seven dots (with
performance being normal for targets of less than seven dots). These deficits
were unrelated to impaired visual acuity, impaired sensitivity to dot density,
and differential positional uncertainty between the eyes of our observers. The
deficits were also unlikely to be due to CSF losses due to abnormal low-spatial
frequency filters involved in detecting long chains of collinear dots. Instead,
the results of simulations indicate that the inefficiency in utilising large
numbers of dots is due to deficits of global, integrative processes in strabismic
amblyopes. These simulations also show that while neither undersampling nor
positional uncertainty of inputs into integrative processes can themselves
account for the amblyopic deficits, if such abnormal inputs lead to the
development of stunted integrative processes then impaired sensitivity to long
chains of collinear dots is indeed predicted.
PMID- 11008147
TI - Harold Hillman MBBS MRCS LRCP BSc PhD.
PMID- 11008148
TI - Aminophylline in the treatment of atropine-resistant bradyasystole.
PMID- 11008149
TI - Anaesthesia and critical care considerations in nerve agent warfare trauma
casualties.
AB - Nerve agents (NA) (tabun, sarin, suman, VX) have been stocked around the world
for some time and still present a major threat to civilian as well as to military
populations. Since NA can be delivered through both an aerial spray system and a
ballistic system, victims could suffer both NA intoxication and multiple trauma
necessitating urgent surgical intervention followed by intensive care. These
patients can be expected to be extremely precarious neurologically, respiratorily
and haemodynamically. Moreover, their clinical signs can be misleading. Further
exacerbating the problem is the fact that interactions of NA with the
pharmacological agents used for resuscitation and/or during anaesthesia can
aggravate organ instability even more and possibly cause systemic collapse. There
are no protocols for perioperative critical care and early assessment or for the
administration of anaesthesia for surgical interventions in such combined
multiple trauma and intoxicated casualties. We propose a scheme for the
administration of critical care and anaesthesia based on the scant anecdotal
reports that have emerged after the occurrence of local accidents involving NA
intoxication and on the neuropharmacological knowledge of the pesticide
organophosphate poisoning database, these compounds being related chemical
substances.
PMID- 11008150
TI - Outcome after cardiac arrest in adults in UK hospitals: effect of the 1997
guidelines.
AB - AIM: To assess the effectiveness of the ILCOR Advisory Statements on Advanced
Life Support adopted by the Resuscitation Council (UK), as the standard for
resuscitation following cardiac arrest. METHOD: Over the period May to November
1997, data on the process and outcome of cardiopulmonary resuscitation following
in-hospital cardiac arrest were collected from 49 hospitals throughout the UK.
RESULTS: Of 2074 audit forms submitted, 1368 were included in the final analysis.
The initial rhythm monitored was ventricular fibrillation (VF) or pulseless
ventricular tachycardia (VT) in 429 patients, of whom 181 (42.2%) were discharged
alive, compared to 6. 2% when the initial rhythm was non-VF/VT. Overall, 240
(17.6%) patients were discharged alive. At 6 months after discharge 195 (82. 3%)
of 237 patients were still alive. Successful initial resuscitation, defined as
return of spontaneous circulation lasting longer than 20 min (ROSC>20 min), was
significantly associated with VF/VT as the initial arrest rhythm, return of
circulation in less than 3 min, age less than 70 years and the use of an advanced
airway (P<0.01). There was a significant increased likelihood of survival to
discharge when the circulation was restored in less than 3 min and age was less
than 70 years (P<0.05). The administration of any adrenaline (epinephrine) was
significantly associated with a reduced likelihood of ROSC>20 min or alive
discharge (P<0.0001). CONCLUSION: Compared to the last major multiple hospital
study published in 1992, the results of this study suggest that there appears to
have been an improvement in survival of in-hospital patients in the UK who have a
VF/VT cardiac arrest. How much of this is directly attributable to the adoption
of the latest guidelines is uncertain.
PMID- 11008151
TI - One-year survival after out-of-hospital cardiac arrest in Copenhagen according to
the 'Utstein style'.
AB - OBJECTIVE: To determine survival after out-of-hospital cardiac arrest (CA) in
Copenhagen, according to the Utstein recommendations, and compare this with other
emergency medical services systems. DESIGN: Register-based cohort study. SETTING:
Copenhagen, population 465000, area 90 km(2). PATIENTS: Consecutive group of
patients with out-of-hospital CA occurring between January 1 1991 and December 31
1993, followed up via the hospital database systems. MATERIALS: Two specially
equipped advanced life support (ALS) units, staffed with an anaesthesiologist and
a specially trained fireman, operating to support basic life support units.
RESULTS: Of 2225 patients who were unconscious without a pulse or breathing, 1461
were declared dead by the anaesthesiologist. Advanced cardiac life support was
initiated in 764, 61 of which were of non-cardiac aetiology. The presumed
aetiology was cardiac in 703: in 235 the event was unwitnessed, in 464 witnessed
and in four the information was missing. Of 464 witnessed CA the initial rhythm
was asystole in 72 cases, in 302 ventricular fibrillation (VF) or ventricular
tachycardia (VT), and in 90 were in other rhythms. In these subgroups discharged
rates were 5 (7%), 62 (21%) and 1 (1%), and 1-year survival rates were 4 (6%), 49
(16%) and 1 (1%), respectively. The median ALS call-response interval was 6 min.
CONCLUSIONS: Survival after CA is more likely if the collapse was witnessed and
in patients with VF/VT of cardiac aetiology.
PMID- 11008152
TI - The attitudes of cardiac arrest survivors and their family members towards CPR
courses.
AB - OBJECTIVES: to evaluate self-assessment of first aid knowledge, readiness to make
use of it in case of a medical emergency and judgement of a 1-day CPR course by
cardiac arrest survivors, their family members and friends as compared to the
general public. BACKGROUND: the recurrence rate of a cardiac arrest after
successful resuscitation is high and most of out-of-hospital cardiac arrests
occur at the patient's home. METHODS: medical students trained in basic and
advanced life support provided 101 members of the target group and 94 of a sex
and age matched control group with a 1-day course in CPR. RESULTS: after the
course, half of the participants in both groups considered their knowledge of
first aid to be very good or good. The readiness to perform first aid in a
medical emergency increased significantly. Of the target group 96% of the
participants as compared with the control group where 91% felt confident to
recognise a cardiac arrest; 79 versus 68% considered themselves capable to
perform CPR if needed. The course was judged as very good in 71 versus 69% and as
good in 25 versus 27% with no differences between groups. CONCLUSION: one-day CPR
courses are well accepted by cardiac arrest survivors, their family members and
friends and help to reduce fears of reacting in medical emergencies. They seem to
be more motivated to gain and use first aid knowledge than others.
PMID- 11008153
TI - Successful out-of-hospital cardiopulmonary resuscitation: what is the optimal in
hospital treatment strategy?
AB - The aim of the study was to evaluate prognostic factors in patients after
successful out-of-hospital resuscitation (sOHR) within 30 min after admission. A
prognostic scoring scale in patients surviving OHR was analysed. We also studied
the effect of these predictive factors and the in-hospital treatment
(percutaneous transluminal coronary angioplasty (PTCA) vs. thrombolysis) on
mortality. We performed a retrospective analysis of the emergency medical system
forms and medical files of 72 consecutive patients aged > or =18 years with sOHR.
Of these 72 patients 37 (51%) met the electrocardiographic and enzymatic criteria
for acute myocardial infarction (AMI). Ten of the 37 AMI patients (27%) underwent
acute PTCA as primary treatment and seven patients (19%) received thrombolytic
therapy for AMI despite prolonged (mean 24+/-13 min) cardiopulmonary
resuscitation (CPR). The remaining 20 patients had no specific infarct treatment.
Despite successful PTCA, in eight out of ten patients, their mortality in
hospital was 60% (6/10). Mortality in the thrombolysis group was 57% (4/7). For
the remaining 20 MI-patients the mortality was 65% (13/20). Univariate and
multivariate analyses were performed to design a weighted prognostic scoring
system. The Glasgow coma scale (GCS) was the strongest independent predictor
(r=0.76, P< or =0.001) for in-hospital death. CONCLUSIONS: in-hospital mortality
after successful OHR seems to largely depend on neurological status at admission
and much less on the specific treatment of myocardial infarction. The prognostic
scoring system accurately predicted the in-hospital mortality and can be used for
early treatment stratification; however, it should be proven in a prospective
study.
PMID- 11008154
TI - Ventricular fibrillation exhibits dynamical properties and self-similarity.
AB - Electrocardiographic recordings of ventricular fibrillation (VF) appear chaotic.
Previous attempts to characterize the chaotic nature of VF have relied on peak-to
peak intervals [Witkowski et al., Phys. Rev. Lett. 1995;75(6):1230-3; Garfinkel
et al., J. Clin. Investig. 1997;99(2):305-314; Hastings et al., Proc. Natl. Acad.
Sci. USA 1996;93:10495-9], the frequency spectrum [Goldberger et al., 1986;19:282
289] or other derived measures [Kaplan and Cohen, Circ. Res. 1990;67:886-92],
with results that demonstrate some characteristics of chaos. We have sought to
determine whether VF is chaotic rather than random and whether the waveform can
be described quantitatively using the tools of fractal geometry. We have
constructed an attractor, measured the correlation dimensions, estimated the
embedding dimension and measured Lyapunov exponents. When the digitized waveform
is analyzed directly, VF exhibits nonrandom, chaotic behavior over a decade of
sampling frequency. Within the scaling range we have estimated the Hurst
exponent, and the self-similarity dimension of the VF waveform, supporting the
presence of chaotic dynamics. Furthermore, these characteristics are measurable
in a porcine model of VF under different recording conditions, and in VF
recordings taken from human subjects immediately prior to defibrillation.
Analyses of the Hurst exponents and self-similarity dimensions are correlated
with the duration of VF, which may have clinical applications.
PMID- 11008155
TI - Ventilation volumes with different self-inflating bags with reference to the ERC
guidelines for airway management: comparison of two compression techniques.
AB - The 1998 ERC-guidelines for airway-management recommend an tidal volume of 400
600 ml for adults undergoing CPR. As commercially available self-inflating bags
were designed to meet former recommendations (800-1200 ml) we investigated how to
meet the latest recommendations with these bags. We combined the head of a
training manikin (Laerdal Medical) and a standard lung (VTTL; Michigan
Instrument), adjusted to a physiological compliance and resistance. Volume was
measured with a Wright spirometer (BOC). Seven self-inflating bags were
investigated. Tests were carried out by ten people (five female and five male)
for 5 min each using two different techniques. Technique 1: standard ventilation
with one hand without compression of the self-inflating bag against the rescuers
knee. Technique 2: modified open palm technique with total squeezing of the self
inflating bag by compression against the rescuers knee. The average tidal volumes
for technique 1 ranged from 438 to 604 ml. Applying technique 2 the volumes
ranged from 888 to 1192 ml. The latest recommendations were met using a single
hand technique without compression against the rescuers knee for all seven bags
tested. The modified open palm technique produced larger tidal volumes which were
more in line with previous recommendations.
PMID- 11008156
TI - Cardiopulmonary resuscitation skills in nurses and nursing students.
AB - The purpose of this study is to describe the basic cardiac life-support (BLS)
skills of nurses and nursing students in southern Finland and Hungary, and to
assess the influence of resuscitation teaching and other group characteristics on
performance. The data for the study were collected in the spring and autumn of
1997. The study group consisted of 75 nurses from Helsinki University Central
Hospital's medical outcome unit, 188 final term students in four nursing
institutes in Uusimaa county and 35 final term students in a Hungarian institute
of nursing. A total of 298 people (34 men and 264 women) participated in the
study. Background information was collected using a structured questionnaire
devised specifically for this study. Resuscitation skills were measured using the
Skillmeter Anne manikin. The manikin was placed supine during the test. After
completing the questionnaire, every participant attempted resuscitation on the
manikin - which was supplied with a printer - for 4 min. The results were printed
out and attached to the questionnaires. The data were analysed using two-way
frequency tables and logistic regression. Statistical differences were calculated
using the chi(2)-test. The results showed that 53% of the participants had
studied resuscitation during the last 6 months, but 7% had never participated in
resuscitation teaching. Before testing, 55% of the participants estimated that
their resuscitation skills were good. The results showed that 36% first assessed
the patient's response, 67% opened the airway but only 3% determined
pulselessness before starting to resuscitate. Twenty-one percent of the
participants compressed correctly for at least half of the test and 33%
ventilated correctly at least half of the time. Logistic regression showed that
the best predictors for good response assessment skills went to those who were
nursing students who had studied resuscitation skills sometime during the
previous 6 months. The best predictor of the skill to open the airway was a
positive attitude towards personal cardiopulmonary resuscitation (CPR) skills,
i.e. self-confidence. The predictor for adequate skills in artificial ventilation
was that they belonged in the group of nursing students who had benefited from
recent resuscitation training (<6 months). In conclusion, the skills of the
participants of the study can not be considered adequate in terms of an adequate
and prompt assessment of the need for resuscitation, and a 50% success rate in
artificial ventilation and chest compression.
PMID- 11008157
TI - Effects of endothelin-1 on resuscitation rate during cardiac arrest.
AB - OBJECTIVES: Endothelin-1 (ET-1) is a potent peripheral and coronary artery
vasoconstrictor and has been shown to improve coronary perfusion pressure (CPP)
during cardiac arrest. The effect of ET-1 on return of spontaneous circulation
(ROSC) following cardiac arrest has not been studied. Our hypothesis was that ET
1 does not improve ROSC from cardiac arrest when compared to placebo. METHODS: A
total of 11 immature swine were used in this laboratory study. Animals were
randomized to receive 300 microg ET-1 and standard dose epinephrine (SDE) or
placebo and SDE during arrest. After a 10-min period of no-flow ventricular
fibrillation (VF), CPR was performed for 3 min followed by ET-1/SDE or
placebo/SDE administration. Following drug administration, standard ACLS was
followed with SDE given every 3 min. Aortic pressure was monitored during
resuscitation. ROSC was defined as any perfusing rhythm with a systolic pressure
greater than 60 mmHg for 60 s. Animals received post-ROSC care as needed for 2 h
post-ROSC. CPP and ROSC were analyzed using repeated measures ANOVA and Fischer's
exact test respectively. P<0.05 was considered significant. RESULTS: Pre-arrest
variables and CPP prior to ET-1 administration were not different between groups.
Following ET-1 administration, CPP was significantly increased at all time points
in ET-1/SDE versus placebo/SDE animals. ROSC was achieved in 1/5 (20%) ET-1/SDE
versus 1/6 (16.7%) placebo/SDE animals (P>0.05). The resuscitated ET-1/SDE animal
survived 6.5 min compared to 120 min for the resuscitated placebo/SDE animal.
CONCLUSIONS: In our study, ET-1 administration during cardiac arrest increases
CPP but does not improve ROSC.
PMID- 11008158
TI - Pentoxifylline improves circulatory and metabolic recovery after cardiopulmonary
resuscitation.
AB - BACKGROUND: To evaluate the effectiveness of a bolus application of
pentoxifylline (PTXF) at the beginning of CPR in a standardized resuscitation
animal model. METHODS AND RESULTS: In a laboratory model of cardiac arrest, 12
Wistar rats (382-413 g) were randomized into two groups. Both groups underwent 4
min of cardiopulmonary arrest induced by a transthoracic application of a
fibrillating current of 10 mA. At the beginning of CPR, group one (n=6) received
a bolus injection of 10 mg kg(-1) body weight PTXF versus sodium chloride in
group two (controls: n=6). All animals developed a severe lactate acidosis during
and after CPR but in PTXF treated animals acid-base values returned to baseline
pattern. During return of spontaneous circulation (ROSC) in the PTXF group
lactate concentration decreased from 13.4+/-2.1 to 1.9+/-0.7 mmol l(-1) within 60
min (P<0.01). In control animals, lactate values remained high (10.8+/-3.5 by 60
min, P<0.01). After bolus injection of PTXF pH increased from 6.93+/-0.06 to
7.29+/-0.13 within 60 min of ROSC versus 6.85+/-0.05 to 6.97+/-0.23 in sodium
chloride treated animals (P<0.01). Within 5 min of ROSC, PTXF treated animals
achieved higher oxygenation values (PTXF P(a)O(2)=216.9+/-62.5 mmHg, control 132.
2+/-15.1 mmHg, P<0.01). CONCLUSIONS: Administration of PTXF at the beginning of
CPR improved macrocirculation, acid-base status and arterial oxygenation.
PMID- 11008159
TI - Alteration of dopamine transport and dopamine D(2) receptor binding in the brain
induced by early and late consequences of global ischaemia caused by cardiac
arrest in the rat.
AB - This study was designed to determine the effects of global cerebral ischaemia
caused by temporary cardiac arrest and the early and late consequences of this
ischaemia on dopamine transport and dopamine D(2) receptor binding in rat brain.
The effects of 10 min of global ischaemia were measured immediately and after 1 h
and 7 days post-resuscitation. A decrease of dopamine uptake in the rats by
synaptosomes was noted immediately following global ischaemia and 1 h after
resuscitation. However, at 7 days post-resuscitation, the dopamine uptake
returned to control values. Reversibility of the changes in the synaptosomal
dopamine uptake is undoubtedly a favourable sign. Global ischaemia and
reperfusion after 1 h or 7 days did not show altered rates of dopamine release
but did affect the dopamine D(2) receptor. An observed increase of receptor
affinity may be an adaptive response to the reduction in binding capacity. The
reduction of visible D(2) receptor binding sites in the early post-resuscitation
phase, which was extended to the period of 7 days after resuscitation without
recovery, is probably associated with neuronal necrotic damage.
PMID- 11008160
TI - Catecholamines in cardiac arrest: role of alpha agonists, beta-adrenergic
blockers and high-dose epinephrine.
PMID- 11008161
TI - A persistent reduction in short-term facilitation accompanies long-term
potentiation in the CA1 area in the intact hippocampus.
AB - Exploration of the nature of the relationship between short-term and long-term
synaptic plasticity should aid our understanding of their roles in brain
function. The effects of inducing long-term potentiation on short-term
facilitation at CA1 synapses in the stratum radiatum of the intact hippocampus
were examined by recording the slope of the field excitatory postsynaptic
potential in both urethane and freely behaving adult rats. Facilitation of the
second synaptic response to paired-pulse stimulation (40ms interstimulus
interval) was monitored before and after the induction of long-term potentiation
by high-frequency stimulation (10 trains of 20 pulses at 200Hz). The tetanus
triggered a rapid overall reduction in paired-pulse facilitation that persisted
for at least 2h. In the anaesthetized animals a detailed correlation analysis
revealed that initial paired-pulse facilitation level correlated strongly with
the subsequent reduction in paired-pulse facilitation and the magnitude of long
term potentiation. The reduction in paired-pulse facilitation also correlated
with long-term potentiation magnitude. These relationships were not observed in
animals with low initial degrees of paired-pulse facilitation. It was concluded
that the relative contribution of different expression mechanisms of long-term
potentiation varies depending on the initial facilitation characteristics of the
synapses. Furthermore, the temporal selectivity and gain control of synapses can
be altered persistently in the intact hippocampus. This suggests that there is
considerable variation in the fidelity of temporal information storage at
different synapses during learning and memory in the CA1 area.
PMID- 11008162
TI - Re-structuring of synapses 24 hours after induction of long-term potentiation in
the dentate gyrus of the rat hippocampus in vivo.
AB - In male rats, long-term potentiation was induced unilaterally in the dentate
gyrus, either by high frequency (200Hz) or theta rhythm stimulation. Structural
synaptic changes were examined 24h after induction using quantitative electron
microscopy. A disector technique was employed in order to estimate the density of
synapses (using 70-80-nm sections) and of granule cell nuclei (using 2-microm
sections) in the middle, and inner molecular layer in both hemispheres. Synaptic
height and total lateral areas of synaptic active zones per unit tissue volume
were assessed via assumption-free stereological techniques coupled with image
analysis. The results obtained indicated that both synaptic density and number
(corrected per neuron) of axo-spinous, but not axo-dendritic, synapses were
approximately 40% higher in the middle, but not inner molecular layer of the
potentiated hemisphere compared to the contralateral (control hemisphere). No
significant inter-hemispheric difference was found in the volume densities of
lateral areas of active zones. These data suggest that 24h after long-term
potentiation induction, active zones of existing axo-spinous synapses either
split forming separate contacts, or decrease in size while new synapses are
formed.
PMID- 11008163
TI - Temporal regularity of neurotransmitter release at single terminal in cultured
hippocampal neurons.
AB - The whole-cell GABA-mediated inhibitory postsynaptic currents were studied using
the patch-clamp technique on synaptically connected cultured hippocampal neurons.
The stimulus-evoked inhibitory postsynaptic currents were recorded in the
tetrodotoxin-containing solution in response to the low-amplitude long (10-20ms)
extracellular depolarization of a single presynaptic terminal. During each
depolarization the postsynaptic response in a form of several superimposed
independent events was recorded. The amplitudes of these responses fluctuated
randomly, irrespective of the number of the event. In all the investigated
neurons the distributions of delays revealed regularly spaced multiple peaks. The
number of peaks increased with the duration of stimulus. The distance between the
peaks was on average 2.97+/-0.86ms (n=58). The mean intervals between successive
releases were distributed exponentially indicating the independence of the
release sites. Thus neurotransmitter release might occur with maximal probability
at the most probable times irrespective of the presence or failure of the
previous event. The increase in stimulating pulse amplitude led to a decrease in
the number of clearly detectable peaks in distributions. The decrease in the
number of peaks in the distribution of delays was not accompanied with a decrease
in the distance between peaks within the range of reliable resolution of the
peaks. The amplitude distribution also revealed regularly spaced multiple peaks.
The absence of significant correlation between the amplitude of the first and the
second event demonstrated the independence of the succeeding release on the
preceding release during long stimulation. Results of statistical analysis of our
experimental data supports the hypothesis of multiquantal neurotransmitter
release in a single inhibitory hippocampal synapse. Neurotransmitter release
during long stimulation may occur at certain times with maximal probability,
keeping the mean inter-release interval constant. Thus the interval is not
determined directly by the depletion of vesicles and the number of vesicles which
may be released at the most probable time is random.
PMID- 11008164
TI - Accumulation of 4-hydroxynonenal-modified proteins in hippocampal CA1 pyramidal
neurons precedes delayed neuronal damage in the gerbil brain.
AB - It has been proposed that reactive oxygen species and lipid peroxidation have a
role in the delayed neuronal death of pyramidal cells in the CA1 region. To
explore the in situ localization and serial changes of 4-hydroxy-2-nonenal
modified proteins, which are major products of membrane peroxidation, we used
immunohistochemistry of the gerbil hippocampus after transient forebrain ischemia
with or without preconditioning ischemia. The normal gerbil hippocampus showed
weak immunoreactivity for 4-hydroxy-2-nonenal-modified proteins in the cytoplasm
of CA1 pyramidal cells. 4-hydroxy-2-nonenal immunoreactivity showed no marked
changes after preconditioning ischemia. In the early period after ischemia and
reperfusion, there was a transient increase of nuclear 4-hydroxy-2-nonenal
immunoreactivity in CA1 pyramidal neurons. In contrast, cytoplasmic
immunoreactivity transiently disappeared during same period and then increased
markedly from 8h to seven days. One week after ischemia, 4-hydroxy-2-nonenal
immunoreactivity was observed within reactive astrocytes in the CA1 region. Early
nuclear accumulation of 4-hydroxy-2-nonenal in CA1 neurons may indicate a
possible role in signal transduction between the nucleus and
cytoplasm/mitochondria, while delayed accumulation of 4-hydroxy-2-nonenal
modified proteins in the cytoplasm may be related to mitochondrial damage. We
conclude that 4-hydroxy-2-nonenal may be a key mediator of the oxidative stress
induced neuronal signaling pathway and may have an important role in modifying
delayed neuronal death.
PMID- 11008165
TI - The hippocampus in spontaneously hypertensive rats: a quantitative
microanatomical study.
AB - The influence of hypertension on the morphology of hippocampus was assessed in
spontaneously hypertensive rats of two, four and six months and in age-matched
normotensive Wistar-Kyoto rats. Values of systolic pressure were slightly
increased in two-month-old spontaneously hypertensive rats in comparison with age
matched Wistar-Kyoto rats and augmented progressively with age in spontaneously
hypertensive rats. No microanatomical changes were observed in the hippocampus of
spontaneously hypertensive rats of two months in comparison with age-matched
Wistar-Kyoto rats, whereas a decrease of white matter volume was observed in the
CA(1) subfield and in the dentate gyrus of four-month-old spontaneously
hypertensive rats. In the hippocampus of six-month-old spontaneously hypertensive
rats a reduction of grey matter volume both in the CA(1) subfield and in the
dentate gyrus, a loss of neurons affecting to a greater extent the CA(1) subfield
and an increase of glial fibrillary acid protein-immunoreactive astrocytes was
found. The occurrence of apoptosis and/or necrosis identified using the terminal
deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick end labelling
technique was also observed in the CA(1) subfield and to a lesser extent in the
dentate gyrus. The only change noticeable in the CA(3) subfield of six-month-old
spontaneously hypertensive rats was a slight increase in the number of glial
fibrillary acid protein-immunoreactive astrocytes. These findings indicate the
occurrence of neuronal loss and of astrocyte changes in the hippocampus of
spontaneously hypertensive rats of six months, being the CA(1) subfield the area
most affected. The relevance of these neurodegenerative changes in hypertension
and the possible occurrence of apoptosis and/or necrosis as expression of
hypertensive brain damage is discussed.
PMID- 11008166
TI - Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F
beta-amyloid precursor protein--initial observations.
AB - Immunohistochemistry was used to analyse 18- and 26-month-old transgenic mice
overexpressing the human beta-amyloid precursor protein under the platelet
derived growth factor-beta promoter with regard to presence and distribution of
neuropeptides. In addition, antisera/antibodies to tyrosine hydroxylase,
acetylcholinesterase, amyloid peptide, glial fibrillary acidic protein and
microglial marker OX42 were used. These mice have been reported to exhibit
extensive amyloid plaques in the hippocampus and cortex [Masliah et al. (1996) J.
Neurosci. 16, 5795-5811]. The most pronounced changes were related to
neuropeptides, whereas differences between wild-type and transgenic mice were
less prominent with regard to tyrosine hydroxylase and acetylcholinesterase. The
main findings were of two types; (i) involvement of peptide-containing neurites
in amyloid beta-peptide positive plaques, and (ii) more generalized changes in
peptide levels in specific layers, neuron populations and/or subregions in the
hippocampal formation and ventral cortices. In contrast, the parietal and
auditory cortices were comparatively less affected. The peptide
immunoreactivities most strongly involved, both in plaques and in the generalized
changes, were galanin, neuropeptide Y, cholecystokinin and enkephalin. This study
shows that there is considerable variation both with regard to plaque load and
peptide expression even among homozygotes of the same age. The most pronounced
changes, predominantly increased peptide levels, were observed in two 26-month
old homozygous mice, for example, galanin-, enkephalin- and cholecystokinin-like
immunoreactivities in stratum lacunosum moleculare, and galanin, neuropeptide Y,
enkephalin and dynorphin in mossy fibers. Many peptides also showed elevated
levels in the ventral cortices. However, decreases were also observed. Thus,
galanin-like immunoreactivity could not any longer be detected in the diffusely
distributed (presumably noradrenergic) fiber network in all hippocampal and
cortical layers, and dynorphin-like immunoreactivity was decreased in stratum
moleculare, cholecystokinin-like immunoreactivity in mossy fibers and substance P
like immunoreactivity in fibers around granule cells. The significance of
generalized peptide changes is at present unclear. For example, the increase in
the mainly inhibitory peptides galanin, neuropeptide Y, enkephalin and dynorphin
and the decrease in the mainly excitatory peptide cholecystokinin in mossy fibers
(and of substance P fibers around granule cells) indicate a shift in balance
towards inhibition of the input to the CA3 pyramidal cell layer. Moreover, it may
be speculated that the increase in levels of some of the peptides represents a
reaction to nerve injury with the aim to counteract, in different ways, the
consequences of injury, for example by exerting trophic actions. Further studies
will be needed to establish to what extent these changes are typical for
Alzheimer mouse models in general or are associated with the V717F mutation
and/or the platelet-derived growth factor-beta promoter.
PMID- 11008167
TI - Differential regulation of adult and embryonic glutamate decarboxylases in rat
dentate granule cells after kainate-induced limbic seizures.
AB - In adult brain, the inhibitory GABAergic neurons utilize two distinct molecular
forms of the GABA-synthesizing enzyme glutamate decarboxylase (GAD), GAD65 and
GAD67. During embryonic development, two truncated forms of GAD67 are also
expressed (GAD25 and GAD44), which are translated from two embryonic-specific
splice variants of GAD67 messenger RNA. It has recently been established that the
excitatory dentate granule cells, in addition to the neurotransmitter glutamate,
also contain low levels of GABA and GAD67, which are increased after limbic
seizures. To study the seizure-induced activation of glutamate decarboxylase, we
investigated the expression of both embryonic and adult glutamate decarboxylase
messenger RNAs in the adult rat hippocampus after kainic acid administration by
semi-quantitative reverse transcription-coupled polymerase chain reaction, in
situ hybridization and immunoblotting. We observed a rapid induction of the
embryonic glutamate decarboxylase messenger RNA in the granule cells of dentate
gyrus. The expression of embryonic glutamate decarboxylase transcripts,
identified here as the splice variant that contains exon 7/B, peaked at about 2h
after kainic acid injection and gradually returned to nearly basal levels by 24h.
Strikingly, this transient induction of embryonic glutamate decarboxylase
messenger RNA was not accompanied by concomitant synthesis of its corresponding
protein product GAD25. In contrast, the adult GAD67 messenger RNA and protein
were both clearly up-regulated in granule cells, albeit with a certain delay,
reaching a maximum around 4-6h after kainic acid injection and gradually returned
to control levels by 24h. GAD65 remained unchanged at both messenger RNA and
protein levels during the studied period. These characteristic and highly
reproducible changes in the synthesis of glutamate decarboxylases indicate that
GAD67 is the predominant form of glutamate decarboxylases involved in the
elevated synthesis of GABA during seizures and suggest that the transient
induction of the embryonic GAD67 messenger RNA that contains exon 7/B, but not
GAD25 protein, may exert a role solely in the subsequent up-regulation of adult
GAD67 transcription. Expression of the messenger RNA encoding for an
alternatively spliced, truncated form of the GABA-synthesizing enzyme glutamate
decarboxylase was detected in dentate granule cells briefly after kainic acid
induced seizures. Just as during embryonic development, expression of the
alternatively spliced messenger RNA was transient and followed by transcription
of its adult form, indicating a possible recapitulation of an embryonic program
of gene expression in adult granule cells after epileptic seizures.
PMID- 11008168
TI - Expression of cholecystokinin, enkephalin, galanin and neuropeptide Y is markedly
changed in the brain of the megencephaly mouse.
AB - Megencephaly, enlarged brain, is a major sign in several human neurological
diseases. The mouse model for megencephaly (mceph/mceph) has an enlarged brain,
presumably due to brain cell hypertrophy, and exhibits neurological and motor
disturbances with seizure-like activity, as well as disturbances in the insulin
like growth factor system. Here, we report that expression of the neuropeptides
cholecystokinin, enkephalin, galanin and neuropeptide Y is dramatically changed
in mceph/mceph brains compared to wild type, as revealed by in situ hybridization
and immunohistochemistry. The changes were confined to discrete brain regions and
occurred in a parallel fashion for peptides and their transcripts. For
cholecystokinin, mceph/mceph brains had region-specific up- and down-regulations
in several layers of the hippocampal formation and increased levels in,
especially ventral, cortical regions. Enkephalin messenger RNA expression was up
regulated in the dentate gyrus granular layer and in ventral cortices, but down
regulated in the CA1 pyramidal layer. Enkephalin-like immunoreactivity was
elevated in mossy fibers of the hippocampus and the ventral cortices. Galanin
expression was increased in several layers and interneurons of the hippocampal
formation, as well as in ventral cortices. Galanin-like immunoreactivity was
reduced in nerve terminals in the forebrain. Neuropeptide Y expression was
increased in the hippocampal formation and ventral cortices. Whether the mainly
increased peptide levels contribute to the excessive growth of the brain or
represent a consequence of this growth and/or of the neurological and motor
disturbances remains to be elucidated.
PMID- 11008169
TI - Maternal corticosterone during lactation permanently affects brain corticosteroid
receptors, stress response and behaviour in rat progeny.
AB - The long-term consequences of a physiological-range increase of maternal
corticosterone during lactation were investigated on the 15-month-old progeny.
The offspring of rats drinking water supplemented with corticosterone (200
microgram/ml of corticosterone hemisuccinate) from day 1 postpartum to weaning
exhibited: (i) better performance in a conditioned learning test; (ii) reduction
of fearfulness in two conflict situations; (iii) lower stress-induced
corticosterone secretion and (iv) higher number of corticosteroid receptors in
the hippocampus. The results of this study show that the effects of maternal
physiological-range hypercorticosteronemia during lactation are lifelong.
Moreover, these data suggest that corticosteroids, secreted during neonatal life,
may constitute a factor directing the neurobiological development of the infant.
In line with this hypothesis, glucocorticoid-induced early events have
consequences on the behavioral and physiological status of adulthood. These
consequences may be either "beneficial" or "detrimental" depending on the plasma
levels of corticosterone induced by the early life occurrences, as well as on the
kind of the stimulus and the developmental stage at which the neonate experiences
the event. The present study demonstrates that, when the increase of
corticosterone in infancy is moderate, the adult rats show reduced anxiety,
improved learning and a better coping strategy to deal with stressful situations.
PMID- 11008170
TI - Reduced number of neurons in the hippocampus and the cerebellum in the postnatal
guinea-pig following intrauterine growth-restriction.
AB - Intrauterine growth restriction is a risk factor for neurological and behavioural
deficits in children although the precise underlying biological correlate for
this is unclear. The present study shows that animals with intrauterine growth
restriction, induced by a period of reduced placental blood flow during the
second half of pregnancy, demonstrate reduced numbers of neurons in the
hippocampus and the cerebellum in conjunction with retarded dendritic and axonal
growth within these structures. Intrauterine growth restriction was induced at 30
days gestational age by unilateral uterine artery ligation in pregnant guinea
pigs. At one week of age, the total number of CA1 pyramidal neurons in the
hippocampus and the Purkinje neurons in the cerebellum were determined using the
combined fractionator/optical disector technique. The Cavalieri Principle was
used to determine the volume of specific regions within the hippocampus and
cerebellum. The body weight of animals that were classified as intrauterine
growth-restricted was reduced by 42% (n=8) compared with control animals (n=8,
P<0.001), while there was a smaller effect on brain weight (16% reduction,
P<0.01). Estimates of the total number of neurons showed a reduction in CA1
pyramidal neurons in growth-restricted animals (4.19+/-0.43x10(5)) compared with
control (5.20+/-0.44x10(5), P<0.01), and the volume of the stratum oriens layer
above the CA1 region, which contains the apical dendrites of the CA1 pyramidal
neurons, was reduced by 21% (P<0.01) in growth-restricted animals. In the
cerebellum there was a reduction in the number of Purkinje neurons in growth
restricted animals (3.97+/-0.50x10(5)) compared with control (5.13+/-0.52x10(5),
P<0.01), and in the volume of the molecular layer (17%, P<0.05), the internal
granular layer (22%, P<0.01) and in the volume of the cerebellar white matter
(23%, P<0.01). These results show that a period of placental insufficiency during
the second half of pregnancy can effect brain development in a way which could
lead to neurological and behavioural deficits in the postnatal animal.
PMID- 11008171
TI - Dopamine in the striatum modulates seizures in a genetic model of absence
epilepsy in the rat.
AB - Inhibition of the substantia nigra pars reticulata has been shown to suppress
seizures in different animal models of epilepsy. The striatum is the main input
of the substantia nigra pars reticulata. The aim of the present study was to
examine the role of dopaminergic neurotransmission within the striatum in the
control of absence seizures in a genetic model in the rat. Injections of mixed
dopaminergic D1/D2 or of selective D1 or D2 agonists or antagonists in the dorsal
parts of the striatum led to suppression of absence seizures associated with
strong behavioral and electroencephalographic side-effects. When injected in the
ventral part of the striatum (i.e. the nucleus accumbens core), all these
agonists and antagonists respectively decreased and increased absence seizures
without behavioral or electroencephalographic side-effects. Combined injections
of low doses of a D1 and a D2 agonist in the core of the nucleus accumbens had an
additive effect in absence seizures suppression. Furthermore, combined injections
of low doses of a GABA(A) agonist and a N-methyl-D-aspartate antagonist in the
substantia nigra also had cumulative effects in absence seizures suppression.
These results show that dopamine neurotransmission in the core of the nucleus
accumbens is critical in the control of absence seizures. The modulatory and
additive effects on absence seizures of dopaminergic neurotransmission through
both the D1 and D2 receptors in the core of the nucleus accumbens further suggest
that ventral pathways of the basal ganglia system are involved in the modulation
of absence seizures.
PMID- 11008172
TI - Activated phosphorylation of cyclic AMP response element binding protein is
associated with preservation of striatal neurons after focal cerebral ischemia in
the rat.
AB - Phosphorylation of the DNA-binding transcription factor, cyclic AMP response
element binding protein, has recently been suggested to provide neuroprotective
signals in times of cellular stress. Medium-sized striatal neurons are among the
cells that are most vulnerable to ischemic stress in the brain. In the present
study, phosphorylation of cyclic AMP response element binding protein was
immunohistochemically evaluated in rat striatum in order to examine the ischemic
vulnerability of each striatal region from the standpoint of cyclic AMP response
element binding protein. Rats were subjected to 90-min focal cerebral ischemia
followed by various periods of recirculation. Focal ischemia was induced by
occlusion of the middle cerebral artery by the intraluminal suture method. Local
cerebral blood flow measured by the 14C-iodoantipyrine method in the lateral and
the medial striatal regions during occlusion was 5.0+/-7. 1 and 42.5+/
8.1ml/100g/min, respectively. Cerebral blood flow in each region was restored to
the control level during the recirculation period. The lateral and the medial
regions of the striatum in the sham animals showed hardly any immunoreactivity
with the specific antibody against phosphorylated cyclic AMP response element
binding protein. By contrast, at 3.5h of recirculation, a number of
phosphorylated cyclic AMP response element binding protein-positive neurons were
detected in the medial striatal region on the occluded side, and the increase in
the number of immunopositive cells continued until two weeks of recirculation
with gradual decline. The lateral striatal region on the ischemic side showed
only a mild increase in phosphorylated cyclic AMP response element binding
protein-positive cells at 3.5h of recirculation, and the immunoreactivity rapidly
disappeared during the subsequent recirculation period. Appreciable increase in
immunoreactive cells was also noted in the contralateral striatum during the
early phase of recirculation, and this increase seemed to be associated with
spontaneous circling movements of the animals. Cresyl Violet staining revealed
that striatal neurons in the medial region remained intact until two weeks of
recirculation, whereas neurons in the lateral striatal region soon showed
ischemic damage, followed by complete neuronal loss, and evolution of a frank
infarct. Immunoreactivity for bcl-2, apoptosis-suppressive protein, was clearly
detected in many neurons in the medial striatal region, but no such
immunoreactivity was detected in the lateral striatal region. These findings
suggest that persistently activated phosphorylation of cyclic AMP response
element binding protein in the striatum during post-ischemic recirculation may be
closely associated with protection of striatal neurons on the ischemic side,
while it may be associated with spontaneous circling movements on the
contralateral side.
PMID- 11008173
TI - Facilitation of learning and long-term ventral pallidal-cortical cholinergic
activation by proteoglycan biglycan and chondroitin sulfate C.
AB - We have shown previously in the rat that biglycan, a recently discovered
chondroitin sulfate proteoglycan, has neurotrophic effects which are mediated by
its chondroitin/dermatan sulfate chains. Here we report that biglycan has
neurochemical effects when injected into the nucleus basalis magnocellularis of
the ventral pallidum, a site of dense cholinergic cell bodies. The effects on the
cholinergic output in the frontal cortex are long lasting, indicating profound
neuroactive function akin to that expected of a long-acting hormone. Injected
into the same area of the brain, as well as into the ventricles in behaviorally
impaired old animals, we found that biglycan can improve learning and memory in
several behavioral paradigms. Furthermore, we show that both the neurochemical
effectiveness as well as the promotion of learning is carried not by the
proteoglycan per se, but rather by its chondroitin sulfate moiety, thus,
demonstrating for the first time memory-promoting and neuroactive effects of a
glycosaminoglycan, namely, chondroitin sulfate C. The results suggest that
biglycan and other extracellular matrix molecules can have neurobehavioral and
pharmacological functions for beyond those traditionally attributed to this class
of molecules.
PMID- 11008174
TI - Impaired spatial learning in aged rats is associated with loss of p75-positive
neurons in the basal forebrain.
AB - We investigated age-related changes in the number and size of neurons positive
for the p75 neurotrophin receptor in the cholinergic basal forebrain of female
Dark Agouti rats. Since the integrity of these neurons is known to be closely
associated with performance in tests of spatial learning ability, we also
investigated the incidence of age-related spatial learning impairments, using the
Barnes maze. Spatial learning impairments occurred with increasing frequency with
age. No rats showed impairment at six months, but 50% were impaired at 14 months
and 71% at 26 months. There was no correlation between age and decreased number
of p75-positive neurons in the rostral basal forebrain, which consists of the
medial septum and vertical limb of the diagonal band of Broca. In the caudal
basal forebrain, which consists of the horizontal limb and the nucleus of
Meynert, there was a 13% reduction in the number of p75-positive neurons at 17
months compared to six months, and a 30% reduction at 26 months. There was a
strong correlation between the presence of spatial learning impairment and a
reduction in the number of p75-positive neurons. This correlation was most
evident in the rostral basal forebrain, but was also present in the caudal basal
forebrain. In the rostral basal forebrain, all learning impaired rats had fewer
p75-positive neurons than the average number in unimpaired rats. A close
correspondence between the presence of p75 and choline acetyltransferase was
evident in basal forebrain neurons of learning-impaired and unimpaired rats.
Gross pathological changes to the morphology of p75-positive neurons were
relatively frequent in learning-impaired rats. These changes consisted of
hypertrophy, appearance of vacuoles, and marginalisation of the cytoplasm. The
results indicate the susceptibility of p75-positive neurons to degenerative
changes with aging, and show that the loss of these neurons in the basal
forebrain was strongly correlated with impairment in spatial learning.
PMID- 11008175
TI - Contributions of mGlu1 and mGlu5 receptors to interactions with N-methyl-D
aspartate receptor-mediated responses and nociceptive sensory responses of rat
thalamic neurons.
AB - The nociceptive responses of rat ventrobasal thalamus neurons can be reduced by N
methyl-D-aspartate antagonists and by selective metabotropic glutamate receptor
mGlu1 antagonists. The recent development of the mGlu5-selective antagonist 6
methyl-2-(phenylethynyl)-pyridine now allows the direct probing of the possible
involvement of mGlu5 receptors in thalamic nociceptive responses. Extracellular
recordings were made from single neurons in the ventrobasal thalamus and
immediately overlying dorsal thalamic nuclei of adult urethane-anaesthetized rats
using multi-barrel electrodes. Responses of neurons to iontophoretic applications
of the mGlu5-selective agonist (R,S)-2-chloro-5-hydroxyphenylglycine were
selectively reduced during continuous iontophoretic applications of 6-methyl-2
(phenylethynyl)-pyridine. Similar applications of 6-methyl-2-(phenylethynyl)
pyridine reduced neuronal responses to noxious thermal stimuli to 53+/-9.5% of
control responses. Co- application by iontophoresis of N-methyl-D-aspartate and
metabotropic glutamate receptor agonists resulted in a mutual potentiation of
excitatory responses. This effect could be reduced by either 6-methyl-2
(phenylethynyl)-pyridine or the mGlu1 antagonist LY367385. These results, taken
together with previous data, suggest that acute thalamic nociceptive responses
are mediated by a combination of mGlu1, mGlu5 and N-methyl-D-aspartate receptor
activation, and that co-activation of these receptors produces a synergistic
excitatory effect. Thus blockade of any of these receptor types would have a
profound effect on the overall nociceptive response.
PMID- 11008176
TI - Calcitonin gene-related peptide receptor expression in the neurons and glia of
developing rat cerebellum: an autoradiographic and immunohistochemical analysis.
AB - Quantitative autoradiography (using [125I]human alpha-calcitonin gene-related
peptide as a ligand) and immunofluorescence (using monoclonal antibodies directed
against a purified receptor) followed by confocal analysis were applied to
analyse the distribution and cellular localization of the calcitonin gene-related
peptide receptor in the rat cerebellum during development. From late embryonic
days to the end of the second postnatal week, during the time window of
calcitonin gene-related peptide expression in climbing fibers, high levels of
calcitonin gene-related peptide binding sites were found in the white matter,
where immunolabeling was present in oligodendrocytes. Lower levels were found in
the cerebellar cortex, where receptor immunolabeling was found in Bergmann glia
in a presumptive cell surface location and, during the second postnatal week,
also in the cytoplasm of Purkinje cells. From the end of the second postnatal
week to adulthood, when calcitonin gene-related peptide is no longer present in
climbing fibers, the number of calcitonin gene-related peptide binding sites
increased in the molecular layer, where not only Bergmann glia but also Purkinje
cell distal dendritic branchlets were immunolabeled in a presumptive cell surface
location. Concomitantly, the number of calcitonin gene-related peptide binding
sites sharply decreased in the white matter. The developmental expression of the
calcitonin gene-related peptide receptor and the previously described
proliferating/differentiating effects of the peptide on glial cells suggest that
calcitonin gene-related peptide and its receptor may promote a coordinated
development of cerebellar glial cells, an effect driven mainly by the calcitonin
gene-related peptide released by climbing fibers. As a result of glia-neuron
interactions, an indirect effect on the differentiation of the cerebellar
neuronal circuitry is also likely to occur.
PMID- 11008177
TI - Group II and group III metabotropic glutamate receptor agonists depress synaptic
transmission in the rat spinal cord dorsal horn.
AB - The effects of group II and group III metabotropic glutamate receptor agonists on
synaptic responses evoked by primary afferent stimulation in the dorsal horn, but
mostly substantia gelatinosa, neurons were studied in the spinal cord slice
preparation using conventional intracellular recording technique. Bath
application of a potent metabotropic glutamate receptor 2- and 3-selective
agonist (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine reversibly
suppressed monosynaptic and polysynaptic excitatory postsynaptic potentials
evoked by A primary afferent fibers stimulation, the effect likely mediated by
mGlu3 receptor subtype. This suppressing effect of (2S,1'R,2'R,3'R)-2-(2',3'
dicarboxycyclopropyl) glycine on primary afferent neurotransmission was dose
dependent and reduced by (S)-alpha-ethylglutamate, a group II metabotropic
glutamate receptor antagonist. (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)
glycine suppressed excitatory postsynaptic potentials without inducing detectable
changes of postsynaptic membrane potential and neuronal input resistance in
dorsal horn neurons. The paired-pulse depression at excitatory synapses between
primary afferent fibers and dorsal horn neurons was reduced by (2S,1'R,2'R,3'R)-2
(2', 3'-dicarboxycyclopropyl) glycine application, suggesting a presynaptic site
of action. The selective group III metabotropic glutamate receptor agonist (S)-2
amino-4-phosphonobutanoate also depressed A afferent fibers-evoked monosynaptic
and polysynaptic excitatory postsynaptic potentials in a dose-dependent and
reversible manner. The concentration-dependence of (S)-2-amino-4
phosphonobutanoate-mediated depression was most consistent with activation of
mGlu receptor subtypes 4 and 7. However, on the basis of anatomical distribution
of mGlu 4 and 7 subtypes, it is also possible that the (S)-2-amino-4
phosphonobatanoate effect is due to interaction with mGlu 7 receptor alone. (RS)
alpha-cyclopropyl-4-phosphonophenylglycine a preferential antagonist at group III
metabotropic glutamate receptors, completely reversed the depressant effects of
(S)-2-amino-4-phosphonobutanoate on both monosynaptic and polysynaptic responses.
(S)-2-amino-4-phosphonobutanoate reduced the paired-pulse depression at
excitatory synapses between primary afferent fibers and dorsal horn neurons, but
did not alter their postsynaptic membrane potential and input resistance. A clear
facilitation of the (S)-2-amino-4-phosphonobutanoate-induced depression of
monosynaptic and polysynaptic excitatory postsynaptic potentials in the absence
of gamma-aminobutyric acid-subtype A receptor- and glycine-mediated synaptic
inhibition was shown. Besides the depressant effect on excitatory synaptic
transmission, inhibitory actions of group II and III metabotropic glutamate
receptor agonists on the inhibitory postsynaptic potentials evoked by primary
afferent stimulation in dorsal horn neurons were observed. These results suggest
that group II and group III metabotropic glutamate receptors are expressed at
primary afferent synapses in the dorsal horn region, and activation of the
receptors suppresses synaptic transmission by an action on the presynaptic site.
PMID- 11008178
TI - Mitogen activated protein kinase inhibition by PD98059 blocks nerve growth factor
stimulated axonal outgrowth from adult mouse dorsal root ganglia in vitro.
AB - Nerve growth factor stimulated axonal outgrowth from explanted mouse dorsal root
ganglia is dependent on mitogen activated protein kinase. PD98059 ([2-(2'amino-3'
methoxyphenyl)-oxanaphthalen-4-one]) blocks mitogen activated protein kinase by
inhibiting its immediate upstream activator, mitogen activated protein kinase
kinase (also known as MEK). Here we used PD98059 to study the role of mitogen
activated protein kinase in the axonal outgrowth of adult dorsal root ganglia
explants. Whereas PD98059 at 50 microM left spontaneous axonal outgrowth
unaffected, it markedly inhibited nerve growth factor stimulated axon growth when
assessed after two days in culture. A mitogen activated protein kinase assay and
immunoblotting using antibodies discriminating between activated and inactivated
kinase, both confirmed that PD98059 reduced the amount of activated enzyme in
nerve growth factor stimulated preparations, while the total amounts of the
kinase remained unchanged. Immunohistochemistry revealed the presence of neuronal
mitogen activated protein kinase kinase and mitogen activated protein kinase
itself. The latter enzyme was found to be activated in the growing axons, as seen
by whole-mount labelling. At the ganglionic level activated mitogen activated
protein kinase was preferentially detected in satellite cells. The results show
that nerve growth factor stimulated axonal outgrowth in vitro from adult mouse
dorsal root ganglia utilizes the mitogen activated protein kinase pathway.
PMID- 11008179
TI - Nerve growth factor maintains potassium conductance after nerve injury in adult
cutaneous afferent dorsal root ganglion neurons.
AB - Whole-cell patch-clamp techniques were used to study the effects of nerve growth
factor on voltage-dependent potassium conductance in normal and axotomized
identified large cutaneous afferent dorsal root ganglion neurons (48-50
micrometer diameter) many of which probably give rise to myelinated Abeta fibers.
K-currents were isolated by blocking Na- and Ca-currents with appropriate ion
replacement and channel blockers. Separation of current components was achieved
on the basis of response to variation in conditioning voltage. Cutaneous
afferents were labeled by the retrograde marker hydroxy-stilbamide (FluoroGold)
which was injected into the skin of the foot. The sciatic nerve was either
ligated or crushed with fine forceps five to seven days later. Neurons were
dissociated 14-17 days after injury. The cut ends of the sciatic nerves were
positioned into polyethylene tubes, which were connected to mini-osmotic pumps
filled with either nerve growth factor or sterile saline. Control neurons
displayed a prominent sustained K-current and the transient potassium currents
"A" and "D". Nerve ligation, which blocks target reconnection resulted in near
50% reduction of total outward current; isolated sustained K-current and
transient A-current were reduced by a comparable amount. Nerve crush, which
allows regeneration to peripheral targets and exposure of the regenerating nerve
to the distal nerve segment, resulted in a small reduction in sustained K-current
but no reduction in transient A-current compared to controls. Levels of transient
A-current and sustained K-current were maintained at control levels after nerve
growth factor treatment. These results indicate that the large reduction in
transient A-current, and in sustained K-current, observed in cutaneous afferent
cell bodies after nerve ligation is prevented by application of nerve growth
factor.
PMID- 11008180
TI - Fmr1 knockout mouse has a distinctive strain-specific learning impairment.
AB - The Fmr1 gene knockout mouse is a model for the human Fragile X mental
retardation syndrome. Fmr1 knockout mice with a C57BL/6-129/OlaHsd hybrid
background have been reported to have only a very mild deficiency in learning the
Morris water maze task. We compared the effect of this knockout mutation on
learning in mice with either an FVB/N-129/OlaHsd hybrid background or a C57BL/6
background. When FVB-129 mice were tested in a cross-shaped water maze task, the
knockout mice showed a pronounced deficiency in their ability to learn the
position of a hidden escape platform in comparison to normal littermates. In
contrast, knockout mice with a C57BL/6 background learned the maze just as well
as their normal littermates. Fear conditioning did not reveal differences between
knockout and normal mice in either background. These results show that silencing
the Fmr1 gene clearly interfered with learning a specific visuospatial task in
FVB/N-129 hybrid mice but not in C57BL/6 mice. The strain dependence may model
the influence of genetic background in the human Fragile X syndrome.
PMID- 11008181
TI - pH modulation of an inward rectifier chloride current in cultured rat cortical
astrocytes.
AB - The effects of changes in extra- and intracellular pH in the pathophysiological
range (6.0-8.0) on astroglial plasma membrane ionic currents were investigated
with the whole-cell patch-clamp technique. In cultured rat neocortical type-1
astrocytes differentiated by a long-term treatment with dibutyryl cyclic-AMP,
exposure to an extracellular pH of 6.4 induced, as compared with the control
extracellular pH at 7.3, a sustained and reversible increase in the holding
current at -60mV. The rise in current was accompanied by a decrease in the
apparent input resistance. Ion substitution experiments indicated that
extracellular pH 6.4 upregulated the resting Cl(-) conductance, whereas an
opposite effect could be observed at extracellular pH 8.0. Recordings of isolated
Cl(-) currents showed that this modulation occurred on the previously identified
hyperpolarization-activated, inwardly rectifying Cl(-) current, I(Clh).
Extracellular acidification to pH 6.4 shifted the voltage dependence of I(Clh)
activation by approximately 20mV towards more positive potentials, whereas a
approximately 20mV opposite shift was observed upon exposure to extracellular pH
8.0. These effects were paralleled by an increase (extracellular pH 6.4) or
decrease (extracellular pH 8.0) in the maximal conductance. Decreasing (6.0) or
increasing (8.0) the intracellular pH shifted the steady-state activation of
I(Clh) towards more negative or positive potentials, respectively, leaving
unchanged the current sensitivity to extracellular pH modifications. The
modulation of the inward rectifier Cl(-) current expressed by differentiated
cultured neocortical astrocytes indicates that extra- and intracellular changes
in pH occurring in a pathophysiological range may contribute to regulating Cl(-)
accumulation in astroglial cells.
PMID- 11008182
TI - Association of persistent falcine sinus with different clinicoradiologic
conditions: MR imaging and MR angiography.
AB - Nine pediatric patients are reported with persistent falcine sinuses associated
with a variety of clinicoradiologic conditions and disorders. Besides MR imaging
studies four patients had MR angiography examinations. Persistent falcine sinus
was associated with arteriovenous malformations in three patients. In two cases
persistent falcine sinus was an incidental finding. In the remaining four
patients persistent falcine sinus was associated with total absence of the corpus
callosum, acrocephalosyndactyly (Apert's syndrome), osteogenesis imperfecta,
Chiari II malformation. The straight sinuses were either absent or rudimentary or
entirely normal in these cases. It can be concluded that a mesenchymal disorder
can be the primary cause for an open falcine sinus either in isolation or in
association with variable changes in the straight sinus.
PMID- 11008183
TI - MRI brain image segmentation by multi-resolution edge detection and region
selection.
AB - Combining both spatial and intensity information in image, we present an MRI
brain image segmentation approach based on multi-resolution edge detection,
region selection, and intensity threshold methods. The detection of white matter
structure in brain is emphasized in this paper. First, a multi-resolution brain
image representation and segmentation procedure based on a multi-scale image
filtering method is presented. Given the nature of the structural connectivity
and intensity homogeneity of brain tissues, region-based methods such as region
growing and subtraction to segment the brain tissue structure from the multi
resolution images are utilized. From the segmented structure, the region-of
interest (ROI) image in the structure region is derived, and then a modified
segmentation of the ROI based on an automatic threshold method using our
threshold selection criterion is presented. Examples on both T1 and T2 weighted
MRI brain image segmentation is presented, showing finer brain tissue structures.
PMID- 11008184
TI - Wavelet based multiresolution expectation maximization image reconstruction
algorithm for positron emission tomography.
AB - Maximum Likelihood (ML) estimation based Expectation Maximization (EM) [IEEE
Trans Med Imag, MI-1 (2) (1982) 113] reconstruction algorithm has shown to
provide good quality reconstruction for positron emission tomography (PET). Our
previous work [IEEE Trans Med Imag, 7(4) (1988) 273; Proc IEEE EMBS Conf, 20(2/6)
(1998) 759] introduced the multigrid (MG) and multiresolution (MR) concept for
PET image reconstruction using EM. This work transforms the MGEM and MREM
algorithm to a Wavelet based Multiresolution EM (WMREM) algorithm by extending
the concept of switching resolutions in both image and data spaces. The MR data
space is generated by performing a 2D-wavelet transform on the acquired tube data
that is used to reconstruct images at different spatial resolutions. Wavelet
transform is used for MR reconstruction as well as adapted in the criterion for
switching resolution levels. The advantage of the wavelet transform is that it
provides very good frequency and spatial (time) localization and allows the use
of these coarse resolution data spaces in the EM estimation process. The MR
algorithm recovers low-frequency components of the reconstructed image at coarser
resolutions in fewer iterations, reducing the number of iterations required at
finer resolution to recover high-frequency components. This paper also presents
the design of customized biorthogonal wavelet filters using the lifting method
that are used for data decomposition and image reconstruction and compares them
to other commonly known wavelets.
PMID- 11008185
TI - Comparison of septal defects in 2D and 3D echocardiography using active contour
models.
AB - Three-dimensional ultrasound is emerging as a viable resource for the imaging of
internal organs. Quantitative studies correlating ultrasonic volume measurements
with MRI data continue to validate this modality as a more efficient alternative
for 3D imaging studies. However, the processing required to form 3D images from a
set of 2D images may result in a loss of spatial resolution and may give rise to
artifacts. This paper examines a method of automatic feature extraction and data
quantification in 3D data sets as compared with original 2D data. This work will
implement an active contour algorithm to automatically extract the endocardial
borders of septal defects in echocardiographic images, and compare the size of
the defects in the original 2D images and the 3D data sets.
PMID- 11008186
TI - Advances in three-dimensional reconstruction of the experimental spinal cord
injury.
AB - Three-dimensional (3D) computer reconstruction is an ideal tool for evaluating
the centralized pathology of mammalian spinal cord injury (SCI) where multiple
anatomical features are embedded within each other. Here, we evaluate three
different reconstruction algorithms to three-dimensionally visualize SCIs. We
also show for the first time, that determination of the volume and surface area
of pathological features is possible using the reconstructed 3D images
themselves. We compare these measurements to those calculated by older
morphometric approaches. Finally, we demonstrate dynamic navigation into a 3D
spinal cord reconstruction.
PMID- 11008187
TI - A case of Streptococcus pneumoniae meningitis showing a marked contrast
enhancement effect of whole arachnoid membrane on MRI.
AB - We have experienced the adult case of meningitis caused by the Streptococcus
pneumoniae, which showed the most aggressive clinical course. The peculiar and
unique magnetic resonance images are reported. The whole arachnoid membrane was
prominently enhanced following the contrast material injection, however, no
contrast enhancement was observed in subarachnoid space, ependyma,
intraventricular cerebrospinal fluid, and dura mater. This implies the superacute
phase of the bacterial meningitis, in which inflammation is localized in the
whole arachnoid membrane. The contrast enhancement effect in the meningitis may
vary depending on the phase and severity, because it is a time-progressive
disease.
PMID- 11008188
TI - Semi-automated color segmentation of anatomical tissue, C. Imielinska, M. S.
Downes, W. Yuan. Computerized medical imaging and graphics 2000;24(3):173-80
PMID- 11008189
TI - Preface to: Proceedings of the Fourth International Symposium on the Treatment of
Parkinson's Disease.
PMID- 11008190
TI - Parkinson's disease is not one disease.
PMID- 11008191
TI - The role of D1-dopamine receptors in working memory-guided movements mediated by
frontal cortical areas.
AB - Like the striatum, the frontal motor cortices receive dopaminergic fibers from
midbrain dopamine cells and contain high levels of dopamine receptors. Among
frontal cortical areas, the dorsolateral PFC (PFd1) and the dorsal premotor
cortex (PMd) have strong neural connections and play a major role for working
memory-guided directional movements. To reveal the role of dopamine in this
cognitive motor function, dopamine antagonists (SCH23390 for D1 receptors and
sulpiride for D2 receptors) were applied locally or iontophoretically to the PFd1
and PMd in monkeys that performed delayed-response tasks with memory-guided
directional movements. Applications of SCH23390, but not sulpiride, to these
areas had significant effects at both the behavioral and neuronal levels. In the
PFd1 and at the behavioral level, local injections of SCH23390 induced specific
errors for memory-guided saccades, whereas it had no effects on visually guided
saccades. In the PMd, local injections of SCH23390 induced directional errors and
increased reaction time and movement time in memory-guided reaching movements. At
the neuron level, iontophoretic applications of SCH23390 attenuated directional
tuning of neurons of the PFd1 and PMd, which showed directional activities during
the delay-and/or response-period(s). These findings suggest that the activation
of D1-dopamine receptors in these frontal cortical areas plays a facilitating
role in a series of neuronal processes of working memory-guided directional
movements; the working memory process for guiding motor act in the PFd1 and
preparation/control of directional manual movements in the PMd. In addition, our
findings may provide insight into symptoms of schizophrenia and Parkinson's
disease; the dysfunction of D1-dopamine receptors in the PMd1 and PMd may
contribute to some symptoms, such as bradyphrenia and bradykinesia, in these
disorders.
PMID- 11008192
TI - Restless legs syndrome and its treatment by dopamine agonists.
AB - The restless legs syndrome (RLS) characteristically presents with an irresistible
urge to move that is most often accompanied by creeping sensations deep in the
limbs. Occasionally the upper limbs can also be affected. RLS symptoms occur at
rest and are typically more intense at night and at bedtime. Some patients
complain about involuntary leg movements, so-called periodic limb movements
(PLM), while at rest or PLM have been observed by the bed partner. Often,
patients have to get out of bed several times at night, to relieve themselves of
their disagreeable sensations.The prevalence of RLS is estimated to be about 5%.
Up to now only three classes of drugs have been systematically evaluated for
treatment of RLS: benzodiazepines, opioids and dopaminergic agents.The most
consistent results have been obtained with dopaminergic drugs. Several studies
have shown that L-dopa given with a peripheral decarboxylase inhibitor at a 10:4
ratio is effective in treating RLS. Controlled studies using polysomnographic
recordings in a double-blind design showed that L-dopa administered at night
produces a significant reduction of RLS occurring at bedtime and of PLM, which
are often associated with nocturnal arousals. In most cases, L-dopa 100mg, in
conjunction with the decarboxylase inhibitor carbidopa or benserazide 25mg,
suppresses RLS although a rebound of PLM may be observed in the last part of the
night. The two major adverse effects frequently seen in patients treated with L
dopa are:Augmentation is one of the limiting factors of L-dopa therapy; thus,
alternative treatment options are of major interest. In several open treatment
trials performed with pergolide, patients reported a marked improvement of RLS
symptoms including sleep problems. Mild symptoms of augmentation under pergolide
treatment have been reported from single patients. In another 6-month open label
trial, pergolide proved to be effective in patients who developed augmentation
under L-dopa by relieving daytime symptoms after switching to pergolide.Most
recently, the results of these open label trials have been replicated in a
randomized, placebo-controlled, double-blind multicenter trial. Treatment with a
single evening dose of 0.25-0.75mg pergolide resulted in a significant
improvement of almost all subjective and objective parameters. Under pergolide,
patients rated their RLS symptoms and sleep disturbances much less severe and
polysomnographic recordings also revealed a significant improvement of all
important sleep parameters. To prevent peripheral side-effects such as nausea or
orthostatic hypotension, pergolide should be slowly up-titrated or domperidone
should be added. Under these conditions, no major side-effects have been observed
in treatment trials with pergolide in dosages up to 1.25mg.Pergolide with a half
life of 12-16h thus appears to be an appropriate drug in the therapy of RLS
especially in those patients who developed augmentation under L-dopa therapy.
Owing to the remarkable therapeutic effect of pergolide on RLS symptom control,
other dopamine agonists are presently being tested for the treatment of RLS.
PMID- 11008193
TI - The early treatment of Parkinson's disease: levodopa, dopamine agonists or both.
AB - Much has been written about the pharmacologic management of Parkinson's disease
(PD) because of an expanding arsenal of antiparkinson drugs and our quest to
alter the natural history of disease. Choice of initial therapy may prove
fundamental to a treatment strategy that maximizes symptomatic control while
minimizing the chances for long-term complications such as motor fluctuations and
dyskinesias. Dopamine agonists (DA) have assumed a primary role in the early
therapy of PD because of their antiparkinson effectiveness and low propensity to
induce fluctuations and dyskinesias. Four available DA in the United States and
an array of recent studies supporting their utility in early PD have shaped
current PD management. Moreover, DA have neuroprotective properties in vivo.
Nevertheless, levodopa remains the most effective drug for symptomatic control in
PD. There is conflicting evidence regarding the putative neurotoxicity of
levodopa and the mechanisms for levodopa-related motor fluctuations are not
entirely known. Clinicians must therefore weigh the available evidence as they
initiate therapy in PD. Clearly, both DA and levodopa will remain essential
components of the early management of PD.
PMID- 11008194
TI - Double blinded evaluation of the effects of pallidal and subthalamic nucleus
stimulation on daytime activity in advanced Parkinson's disease.
AB - The results of a double blinded evaluation of the effects of globus pallidus
(GPi; n=7) and subthalamic nucleus (STN; n=11) stimulation in patients with
advanced Parkinson's disease are summarized. The patients were evaluated at 6
8months after surgery. In order to determine the benefits afforded by the
stimulation to the actual daily activities, the patients were maintained on
medication with optimal doses and schedules. The stimulation was turned off
overnight for at least 12h. It was turned on in the morning (or maintained turned
off), and the best and worst scores during daytime activity were recorded, as on
period and off-period scores, respectively. A reduction in total motor score on
the Unified Parkinson's Disease Rating Scale was clearly elicited by GPi and STN
stimulation at both the off-period (-57 and -29%, respectively) and the on-period
(-36 and -25%, respectively). The difference in effects between GPi and STN
stimulation appeared to be due largely to an unintended difference in the
patients' preoperative symptoms. The benefits provided by stimulation to the
actual daily activities appears to be limited in patients who have become
unresponsive to a large dose of levodopa. Two advantages of GPi and STN
stimulation were identified. Firstly, the stimulation can supplement a reduced
action of levodopa during the off-period. It thus improves the patient's daily
activities through attenuation of the motor fluctuations. Secondly, the
stimulation can replace part of the action of levodopa during the on-period. It
thus attenuates dopa-induced dyskinesia through a reduced dose of medication.
More importantly, the stimulation improves the daily activities in dopa
intolerant patients who are being administered a small dose of levodopa because
of unbearable side effects. In addition, GPi stimulation has its own inhibitory
effect on dopa-induced dyskinesia. Clinically important improvement was observed
in severe gait freezing in 2 patients following unilateral anterodorsal GPi
stimulation on the right side alone.
PMID- 11008195
TI - Management of behavioral and psychiatric problems in Parkinson's disease.
AB - Behavioral and psychiatric problems associated with idiopathic Parkinson's
disease (PD) include cognitive dysfunction, drug-related psychosis, depression,
anxiety, apathy, fatigue and sleep disturbance. These nonmotor symptoms are a
significant cause of disability at all stages of illness. Cognitive dysfunction
spans a continuum from circumscribed cognitive impairments to severe global
dementia which can occur in up to 10-30% of advanced PD patients. Psychosis
develops in 20-30% of PD patients receiving chronic antiparkinsonian therapy.
Visual hallucinations and paranoid delusions are the most frequent symptoms. The
gradual elimination of drugs of lesser priority that may affect cognition and/or
cloud the sensorium constitutes the first step in the management of cognitive and
psychotic symptoms. Atypical neuroleptic agents are an invaluable tool in those
cases in which maximum drug regimen simplification is not adequate or results in
unacceptable immobility. Depression and anxiety often go unrecognized although
they are eminently treatable and may be important contributors to the morbidity
of PD. They are present in 30-40% of PD patients and frequently occur together in
association with other nonmotor symptoms such as apathy, fatigue and sleep
disturbance. A combination of early recognition, counseling, antidepressant
therapy, antianxiety and well-balanced antiparkinsonian therapy sets the stage
for improved quality of life for patients with PD.
PMID- 11008196
TI - Dopamine agonists: the treatment for Parkinson's disease in the XXI century?
AB - Levodopa combined with a peripheral dopa-decarboxylase inhibitor (DCI) has been
considered the therapy of choice for Parkinson's disease (PD). Levodopa is nearly
always effective, but has a high incidence of adverse effects with long term use,
including response fluctuations (on/off phenomena) and dyskinesias. Dopaminergic
agonists, acting directly at the receptor level, would be able to decrease the
incidence of these motor complications.In progressive neurodegenerative diseases,
such as PD, modification of the rate of disease progression (often referred to as
neuroprotection) is currently a highly debated topic. Increased oxidative stress
is thought to be involved in nigral cell death, that is characteristic of PD.
This oxidative stress may be further exacerbated by levodopa therapy. These
mechanisms have been proven in vitro and animal models, but it's relevance in
humans remains speculative.Based on the considerations above, the emerging
therapeutic strategies for PD advocate early use of dopamine agonists in the
treatment of PD. A number of recent well-controlled studies have proven the
efficacy of dopamine agonists used as monotherapy. Moreover, as predicted by
animal studies, on the long term, dopaminergic agonists induce significantly less
motor complications than levodopa.In the last 2years, three new dopamine agonists
have been launched, including ropinirole, pramipexole and cabergoline. These new
agonists have been added, as therapeutical options to well-established drugs,
like pergolide, bromocriptine or talipexole. The recently launched compounds have
proven efficacy in monotherapy and as adjunctive therapy to levodopa.
Unfortunately, only a very limited amount of comparative data among the different
agonists is available. Pergolide has proven to be a superior drug to
bromocriptine as adjunctive therapy to levodopa in a significant number of
studies and is considered the gold standard dopamine agonist. Nevertheless, none
of the recently launched compounds has compared itself against pergolide.A
comparison of monotherapy trials is difficult, because of differences in design
and populations. In a recently completed trial pergolide was statistically
significantly better than placebo in all the efficacy parameters tested, with 57%
of pergolide treated patients improving over 30% in the motor section of the
UPDRS, as compared to 17% in the placebo arm. Interestingly, these results were
obtained in the absence of any other antiparkinsonian drug during the trial.
Recent monotherapy trials done with ropinirole and pramipexole achieved also
significant improvements as monotherapy, but in these cases selegeline, a drug
that causes a symptomatic improvement in PD, was allowed as co-medications during
the trial. Not all trials used the same efficacy measures, i.e. monotherapy
trials with pergolide and ropinirole used a "responder" based analysis (responder
were all patients that improved 30% or more on the motor section of UPDRS), as
well as a baseline to endpoint improvement in motor scores. Pramipexole
monotherapy trials used only the latter approach, which is clinically less
powerful than a responder analysis.Even with the difficulties mentioned above,
all the recent trials with dopamine agonists have proven that these drugs are a
useful symptomatic long term treatment for PD with or without levodopa and that
the early use of dopamine agonists reduces the incidence of motor complications
as compared to levodopa.
PMID- 11008197
TI - Treatment of early Parkinson's disease.
AB - Levodopa is still the most effective therapeutic agent for the treatment of
Parkinson's disease (PD). Initially, levodopa provides a stable therapeutic
response but, during long-term treatment its beneficial effect declines and a
gradually increasing number of patients experience fluctuations in motor
response. Therefore, in the management of PD it is important to minimise the
risks for the development of motor fluctuations. In this context, recent double
blind long-term studies have confirmed the earlier results, suggesting that it
appears advisable to initiate dopaminergic treatment in early PD by initially
using a dopamine agonist and by adding levodopa when the benefit is no longer
adequate with dopamine agonist alone. Another alternative would be to start with
selegiline alone, then depending on the disability of the patient, add a dopamine
agonist and finally levodopa.
PMID- 11008198
TI - Diagnosis and differential diagnosis of Parkinson's disease and parkinsonism.
AB - In the clinic setting, most cases represent either Parkinson's disease (PD) or
one of the other neurodegenerative disorders that make up the parkinsonism-plus
syndromes. The major parkinsonism-plus syndromes include progressive supranuclear
palsy, multiple system atrophy, corticobasal degeneration, as well as
parkinsonism occurring in the context of Alzheimer's disease or one of the other
primary dementing disorders. There are a variety of other conditions, however,
that occasionally come into the differential diagnosis. These fall into the
categories of secondary parkinsonism (due to drugs, toxins, structural lesions,
etc.), another tremor syndrome such as essential tremor, or a hereditary disorder
with parkinsonism. This broad differential diagnosis is reviewed.
PMID- 11008199
TI - Treatment of Parkinson's disease in Japan.
AB - In this paper, the course of therapy for Parkinson's disease is outlined. The
rationale for the use of DA-receptor-agonist (DA agonist) monotherapy or early
combination therapy using levodopa and a DA agonist is that these therapies are
asociated with a lower incidence of motor complications. However, the disease
progresses, the use of levodopa in combination with a DA agonist results in motor
complications and development of levodopa dependency in parkinsonian patients,
because the effect of levodopa on parkinsonism is very strong. In this study, a
positive correlation between the Hoehn-Yahr severity score at off-periods and
duration of illness was observed in parkinsonian patients with long duration of
illness. This indicates that responsiveness to dopaminergic therapy still exists
even in patients in advanced stages of Parkinson's disease, indicating that
continuous stimulation of DA receptors and reducing the excessive fluctuation in
the plasma levodopa level possibly improve motor complications. If the dose of
the DA agonist is simply increased without reduction of levodopa doses,
dyskinesia worsens. Although levodopa therapy is essential in the case of
patients in advanced stages of Parkinson's disease, the therapeutic principle,
which depends on levodopa efficacy, must be changed. Reduction of the levodopa
dose and administration of a sufficient dose of a DA agonist, which is equivalent
to levodopa dose reduction, is one of the possible means of effective therapy of
the disease.
PMID- 11008200
TI - C-MYC expression in medulloblastoma and its prognostic value.
AB - To identify prognostic factors in medulloblastoma, a common malignant brain tumor
of childhood, expression of the oncogene c-myc was examined at the mRNA level by
in situ hybridization. c-myc mRNA expression was observed in 30 of 72 tumors
(42%). The c-myc gene copy number was determined by quantitative PCR from genomic
DNA of paraffin-embedded tumors. c-myc gene amplification was present in 5 of 62
cases (8.3%). Therefore, c-myc amplification was obviously not the cause of c-myc
mRNA expression in most samples. Kaplan-Meier estimation revealed a significant
correlation between c-myc mRNA expression and survival (total mean follow-up 4.6
+/- 3.6 years, log-rank p = 0.02). Multivariate logistic regression analysis
including sex, age, histological type, degree of surgical resection and
expression of synaptophysin, GFAP and c-myc, was carried out on 54 patients who
received both radiotherapy and chemotherapy. The analysis identified expression
of c-myc as an independent predictive factor of death from disease.
PMID- 11008201
TI - Gene amplifications detected by fluorescence in situ hybridization in pure
intraductal breast carcinomas: relation to morphology, cell proliferation and
expression of breast cancer-related genes.
AB - Investigation of early breast carcinogenesis is limited by the difficulty in
obtaining cell cultures or adequate fresh frozen material and by the fact that
available data from in situ techniques are interpreted in terms of various
classification systems. Our studies in a series of pure ductal carcinomas in situ
(DCIS) were conducted in accordance with the recommendations of the international
Consensus Conference (Hum. Pathol., 28, 122-125, 1997) relative to processing,
determination of lesion extent, and histological stratification primarily on
nuclear grade (NG). A multifactorial study performed in 15 low- and 16 high-NG
DCIS (68% detected by mammography) included the following: (1) morphological
analysis of NG, necrosis, and architectural pattern; (2) detection of numerical
genomic abnormalities at ERBB2, MYC, CCND1, Xq1.2 and 20q13 loci by fluorescence
in situ hybridization on interphase nuclei; and (3) immunohistochemical
determination of cell proliferation, p53 accumulation, hormonal receptors and bcl
2 expression on serial sections of formalin-fixed, paraffin-embedded specimens.
High NG, comedo/solid pattern and necrosis were significantly associated with
amplification at one or more loci, the number of amplified loci, amplification at
the ERBB2 locus, absence of bcl-2 and hormonal receptor expression and high cell
proliferation (p < 0.05). High NG and comedo/solid pattern were significantly
associated with MYC amplification and p53 accumulation, and necrosis with CCND1
amplification (the only gene amplification detected in low NG DCIS). These data
provide additional information on the early steps of breast carcinogenesis, in
accordance with currently recognized criteria of histological classification.
PMID- 11008202
TI - Rapid quantitative detection of carcinoembryonic antigen-expressing free tumor
cells in the peritoneal cavity of gastric-cancer patients with real-time RT-PCR
on the lightcycler.
AB - Detection of free cancer cells in the peritoneal cavity by RT-PCR using
carcinoembryonic antigen (CEA) as a target gene is a more sensitive predictor of
peritoneal dissemination than conventional cytology in gastric-cancer patients.
Difficulties with this method are the lack of quantitative assessment of free
cancer cells and the length of time before completion. To overcome these
problems, we have established a rapid and quantitative detection method using a
novel real-time fluorescence PCR system (LightCycler). Using this device with
hybridization probes as fluorophores, we detected CEA mRNA in peritoneal washes
during surgery (within 3 hr) without any post-PCR procedure. This method could
reproducibly quantitate 10 to 10(6) CEA-expressing colon carcinoma cells per
10(7) peripheral blood leukocytes, a comparable sensitivity to conventional RT
PCR with a wide dynamic range. Analysis of peritoneal washes from 109 gastric
cancer patients with this assay revealed relative values of CEA transcripts that
correlated well with the depth of tumor invasion (p < 0.01). Average values of
CEA transcript in peritoneal washes in patients with cytology (-)/RT-PCR(-),
cytology (-)/RT-PCR(+) and cytology (+)/RT-PCR(+) results were 0.64, 1,525 and
6,715, respectively. Moreover, CEA transcripts in peritoneal washes in patients
with synchronous peritoneal metastasis were more than 50-fold higher than in
those without metastasis. These results suggest a positive correlation between
CEA mRNA levels in peritoneal washes and prognosis. We conclude that real-time RT
PCR with hybridization probes is a sensitive, quantitative, specific and rapid
method to detect free cancer cells in peritoneal washes. This clinically relevant
system is a powerful technique to evaluate the risk of peritoneal recurrence in
patients with gastric cancer.
PMID- 11008203
TI - Expression of glypican 3 (GPC3) in embryonal tumors.
AB - Embryonal tumors, such as neuroblastoma, medulloblastoma and Wilms' tumor, have
their peak incidence in the first 4 years of life. These neoplasias exhibit
genetic and clinical heterogeneity, but little is known about their molecular
pathogenesis. Application of the differential-display PCR approach led to the
identification of a gene, glypican 3 (GPC3), that is differentially expressed in
cancer cells. Expression of this gene is usually limited to fetal mesodermal
tissue, and its inactivation has been found to be responsible for the X-linked
Simpson-Golabi-Behmel overgrowth syndrome. Here, we show that GPC3 mRNA is
present in several neuroblastomas and all Wilms' tumors tested to date but not in
medulloblastoma. GPC3 was not expressed in normal kidney tissues obtained from
the corresponding Wilms' tumor patients, suggesting that in these cancer cells
expression was not repressed (or was activated). No correlation was found between
expression of GPC3 and the known indicator of neuroblastoma prognosis MYCN mRNA.
However, all samples that expressed GPC3 also expressed IGF-II, coding for a
growth factor important in the survival and growth of many cancer types. Although
the biological significance of this relationship remains unclear, our results
suggest that GPC3 may be implicated in the development of embryonal tumors
through a signaling pathway that appears to involve IGF-II.
PMID- 11008204
TI - Bcl-2 expression is associated with improved prognosis in patients with distal
colorectal adenocarcinomas.
AB - Several recent studies have suggested that the anatomic location of the tumor and
ethnicity of the patient should be considered in the evaluation of prognostic
markers of colorectal neoplasia. The phenotypic expression of Bcl-2 has been
reported to be a useful prognostic marker in colorectal adenocarcinoma (CRC).
However, its prognostic importance in CRCs based on their anatomic location and
on the ethnicity of the patients has not been reported. Therefore, we evaluated
Bcl-2 expression by immunohistochemistry in CRCs collected from 107 African
American and 149 Caucasian patients from a southern U.S. population. In
univariate Kaplan-Meier survival analyses, Bcl-2 expression was associated with
better overall survival of both African-American (log-rank, p = 0.040) and
Caucasian (log-rank, p = 0.032) patients with distal but not with proximal CRCs.
In multivariate Cox regression analyses, when the pathologic features of tumors
were not included, the expression of Bcl-2 was associated with better survival in
either ethnic patient populations with distal CRCs after adjusting for other
confounding variables and p53(nac) status; however, it was not significant in
either race when tumor stage was included in multivariate analyses. Thus, these
studies suggest that the expression of Bcl-2 in CRCs is a valuable indicator of
good prognosis in either race when CRCs are located in the distal colorectum.
Also, these studies suggest that the expression of Bcl-2 is useful in determining
prognosis before pathologic-clinical staging and it can aid in selection of
treatment after evaluation of diagnostic biopsy specimens of patients with distal
colorectal adenocarcinomas.
PMID- 11008205
TI - Urokinase-type plasminogen activator and its receptor in colorectal cancer:
independent prognostic factors of metastasis and cancer-specific survival and
potential therapeutic targets.
AB - Urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plasminogen
(Plg), and plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) have been
observed in many cancers and may contribute to progression and metastasis. In our
study, we examined the expression of the 5 proteins by immunohistochemistry in 59
consecutive primary colorectal cancers (CRC) and correlated the protein
expression with patient outcome. In addition, we determined the effect of down
regulation of uPAR on the invasive/metastatic capability of CRC cells, by
measuring antisense-uPAR transfected HCT116 and control cell lines, in terms of
uPAR expression, uPA-binding activity, invasiveness through Matrigel in vitro and
metastasis after cecal orthotopic implantation in nude mice in vivo. We found
that higher expression of uPA or uPAR in primary tumor tissues was positively
correlated with distant metastasis of CRC (Mann-Whitney, p < 0.02) and negatively
correlated with both patient overall survival (OS) and cancer-specific survival
(CSS; Cox model, p < 0.04). The prognostic value of uPA and uPAR for both OS and
CSS was independent of other variables (multivariate Cox model, p < 0. 007).
Antisense-uPAR transfected HCT116 cells, which expressed significantly lower
levels of total cellular and cell surface uPAR proteins and uPA-binding activity
compared with either wild-type or cells transfected with vector alone
(Bonferroni, p < 0.05/3), consistently showed decreased invasiveness through
Matrigel (Bonferroni, p < 0.05/3) and decreased metastasis formation in nude mice
(Fisher, p < 0.05). Our data suggest that uPAR and uPA are independent prognostic
factors in CRC; anti-uPAR treatment, which affects both uPAR and uPA levels, may
have potential for new treatment of the disease.
PMID- 11008206
TI - Nucleolus organizer regions (AgNORs) and total tumor mass are independent
prognostic parameters for treatment-free period in chronic lymphocytic leukemia.
AB - The aim of our study was to evaluate whether the nucleolus organizer regions
(AgNOR) of circulating lymphocytes in chronic lymphocytic leukemia (CLL) could
predict the duration of the stable phase (treatment-free period) of this disease.
Age, sex, peripheral lymphoctes, hemoglobin, platelet count, Binet's stage, total
tumor mass (TTM) and AgNOR pattern at diagnosis were assessed in 57 patients and
compared with the time from diagnosis until patients fulfilled the criteria to
start chemotherapy. In univariate Cox regression, Binet's stage, hemoglobin,
number of peripheral lymphocytes, TTM and the percentage of lymphocytes
containing one AgNOR cluster (circulating proliferative fraction) had predictive
value. In the multivariate Cox model, only TTM and the percentage of cells with
one AgNOR cluster were independent factors predicting the duration of the stable
phase. Repetition of these analyses in 500 data sets created by bootstrap
resampling confirmed the results. Summing up the percentage of lymphocytes with
an AgNOR cluster and the TTM value, a simple prognostic index could be created to
give information about the duration of the stable phase in CLL.
PMID- 11008207
TI - Microsatellite instability, prognosis and metastasis in gastric cancers from a
low-risk population.
AB - We examined 169 cases of gastric adenocarcinoma for microsatellite instability
(MSI), using a panel of 8 microsatellite markers. Of these cases, 142 were from
the United States, a country of relatively low risk for gastric cancer. Comparing
microdissected tumors to normal cells from the same patient, we classified tumors
as being microsatellite-stable (MSS) or having a low frequency of MSI (MSI-L, up
to 30% of markers different in the tumor) or a high frequency of MSI (MSI-H, 30%
or more of markers different). Among our American cases, we identified 26 (18.2%)
showing MSI-H and 15 (10.6%) showing MSI-L. Twenty cases were from Korean
patients, and they showed no significant differences in proportions of MSI-H and
MSI-L from the American cases. MSI-H tumors in the American patients were
characterized by elevated frequencies of band shifts in repeat sequences of the
BAX (50%), transforming growth factor-beta receptor type II (TGFbetaRII, 68.9%),
beta(2)-microglobulin (21.4%) and E2F4 (51.7%) genes. Alterations in E2F4 in MSI
H tumors were always integral multiples of 3 nucleotides lost or gained, which
would not cause a frameshift mutation, and within the range of normal
polymorphisms for this sequence. North American patients (n = 127) with MSI-H and
MSI-L tumors had a longer median survival of 541 days and 587 days, respectively,
compared to 265 days for patients with MSS tumors (p = 0.027). This survival
difference may result from a significantly greater tendency for metastases in the
MSS group (p = 0.031).
PMID- 11008208
TI - ERCC1 expression as a molecular marker of cisplatin resistance in human cervical
tumor cells.
AB - Cisplatin is a valuable adjuvant to radiotherapy for the treatment of cervical
cancer. Because the advantage of combining cisplatin with radiotherapy is likely
to be attributable to additive cell killing by these 2 agents, such protocols
should primarily benefit patients who have inherently cisplatin-sensitive tumors.
Development of a molecular assay to rapidly evaluate the cisplatin responsiveness
of cervical tumors would thus be extremely valuable. We investigated whether high
pre-treatment mRNA levels of the ERCC1 nucleotide excision repair gene are
predictive of cisplatin resistance in early-passage human cervical cancer cells,
as they are in several other tumor types. Expression of the ERCC1 gene at the
mRNA and protein levels was established by Northern and Western blotting,
respectively, in a panel of single-cell-derived cervical carcinoma cell lines
that exhibited a wide range of inherent sensitivity to cisplatin. There was a
significant (p = 0.011) correlation between ERCC1 mRNA levels and cisplatin
resistance in these cell lines. However, there was no obvious relationship
between ERCC1 protein levels and cisplatin resistance. Thus, the association
between high ERCC1 mRNA levels and cisplatin resistance might be an
epiphenomenon. Nonetheless, pre-treatment ERCC1 mRNA levels may be a useful
molecular marker for identifying cervical tumors likely to be refractory to
cisplatin, and further investigation in clinical biopsy material is warranted.
PMID- 11008209
TI - Genetic polymorphisms of p53 and GSTP1,but not NAT2,are associated with
susceptibility to squamous-cell carcinoma of the esophagus.
AB - The interaction of genetic and environmental factors can determine an
individual's susceptibility to various cancers. We present a hospital-based case
control study, which included 90 patients of esophageal squamous-cell carcinoma
(ESCC) and 254 healthy people in Taiwan, to investigate the effects of genetic
polymorphisms of p53, GSTP1 and NAT2 on the risk of ESCC. Polymorphisms of p53,
NAT2 and GSTP1 were determined by PCR-RFLP. The codon 72 p53 Pro allele was more
frequently found in ESCC patients [odds ratio (OR) 1.86, 95% confidence interval
(CI) 1.04-3.35 for Arg/Pro genotype and OR 2.56, 95% CI 1.29-5.08 for Pro/Pro
genotype]. In cigarette smokers, the frequency of GSTP1 Ile/Ile genotype was
higher in ESCC patients (OR 2.8, 95% CI 1.4-5.7). Among alcohol drinkers,
borderline significance was also found for GSTP1 Ile/Ile genotype (OR 2.0, 95% CI
0.9-4.4). Results were not similar for the NAT2 genetic polymorphism. Using
logistic analyses, we found that individuals with p53 Pro/Pro genotype had a
significantly higher risk of developing ESCC than those with Arg/Arg genotype (OR
2.3, 95% CI 1. 1-5.1), after adjusting for other significant environmental risk
factors. This result remained similar (OR 2.2, 95% CI 1.0-4.8 for p53 Pro/Pro vs.
Arg/Arg), even after further adjustment for NAT2 and GSTP1 polymorphisms. The
codon 72 p53 Pro/Pro genotype in the general population and GSTP1 Ile/Ile in
cigarette smokers may predict a higher risk of developing ESCC.
PMID- 11008210
TI - BCAR1/p130Cas expression in untreated and acquired tamoxifen-resistant human
breast carcinomas.
AB - High BCAR1/p130Cas expression in primary breast tumour cytosol predicts a poor
chance of response recurrent disease to tamoxifen treatment in patients with
oestrogen receptor (ER)-positive breast carcinomas. In this study, we assessed
whether BCAR1/p130Cas expression is altered during acquisition of anti-oestrogen
resistance. BCAR1/p130Cas protein was quantitatively measured by chemiluminescent
Western blot analysis in the cytosol of 34 predominantly ER(+) carcinomas that
initially responded to primary tamoxifen treatment and subsequently progressed (n
= 22 ) or developed during adjuvant tamoxifen treatment (n = 12) and compared to
54 untreated ER(+) human breast carcinomas. We did not detect significant
differences in the level of BCAR1/p130Cas protein in untreated and acquired
tamoxifen-resistant carcinomas. Our results indicate that in tumour progression
towards tamoxifen resistance, increase of BCAR1/p130Cas may be only one of the
molecular mechanisms. Thus, high BCAR1/p130Cas protein levels appear to be a
hallmark for intrinsic resistance to tamoxifen in breast carcinomas.
PMID- 11008211
TI - Influence of laminin-2 on Schwann cell-axon interactions.
AB - The dy/dy mouse suffers from a form of muscular dystrophy caused by a substantial
reduction in laminin alpha2-chain protein, a major component of both muscle and
Schwann cell basal laminae. This article examines the effect of laminin alpha2
deficiency on Schwann cell-axon interactions both in vivo at varying intervals
after nerve crush, and in vitro, in cocultures of neurons and Schwann cells. The
morphological spectrum of aberrant Schwann cell-axon associations seen in
uncrushed dy/dy sciatic nerves was recapitulated during regeneration: myelination
of regenerating axons was delayed compared with the process in unaffected mice
and the relatively few myelin sheaths which were formed in dy/dy distal nerve
stumps were often uncompacted. In vitro, Schwann cells dissociated from adult
dy/dy sciatic nerves predictably failed to express detectable laminin alpha2
chain and displayed an unusual multipolar morphology. Branching of neurites, in
terms both of numbers of terminal branches and of complexity of branching, from
dorsal root ganglia neurons grown on dy/dy Schwann cells, was significantly less
extensive than that seen when neurons were cocultured with Schwann cells from
unaffected littermates, but this effect was reversed by exogenous laminin-2. Our
results lend strong support to the view that laminin-2 is essential for
establishing and/or maintaining Schwann cell-axon interactions, in normal and in
regenerating nerves.
PMID- 11008212
TI - Hydrostatic pressure stimulates synthesis of elastin in cultured optic nerve head
astrocytes.
AB - Elastin is a major component of the extracellular matrix (ECM) of the lamina
cribrosa in the optic nerve head in humans and nonhuman primates. The lamina
cribrosa appears to be the site of damage to the retinal ganglion cell axons in
glaucomatous optic neuropathy, characterized in many patients by elevated
intraocular pressure (IOP). Type 1B astrocytes are the major cell type in the
lamina, synthesize elastic fibers during development, express increased elastin
mRNA, and synthesize abnormal elastin in glaucoma. In this study, we determined
the effect of elevated hydrostatic pressure on the synthesis of elastin by type
1B astrocytes in culture. Type 1B astrocytes were exposed to gradients of
hydrostatic pressure and tested for proliferation, morphology, synthesis, and
deposition of elastin. Trichloroacetic acid (TCA) and immunoprecipitation of
radiolabeled protein determined total new protein and elastin synthesis. Proteins
from the conditioned media were analyzed by Western blot. Levels of elastin mRNA
were determined by in situ hybridization. Cell proliferation increased
approximately 2-fold after exposure to pressure for one day, approximately 5-fold
after 3 and 5 days of exposure to pressure. Confocal and electron microscopic
cytochemistry showed a marked increase in intracellular elastin in astrocytes
exposed to pressure, as compared with controls. Intracellular elastin was
associated with the RER-Golgi region and with the cytoskeleton. Total protein and
elastin synthesis increased significantly (P < 0.05) at 3- and 5-day exposure to
pressure, as well as the level of elastin mRNA. Elastin protein in the media
increased with the level of pressure. These results indicate that hydrostatic
pressure stimulates type 1B astrocytes to synthesize and secrete soluble elastin
into the media. In glaucoma, type 1B astrocytes may respond to IOP-related stress
with increased expression of elastin and formation of elastotic fibers leading to
loss of elasticity and tissue remodeling.
PMID- 11008213
TI - Biomodulatory role of ceramide in basic fibroblast growth factor-induced
proliferation of cerebellar astrocytes in primary culture.
AB - To evaluate the role of ceramide in glial growth, primary cultures of quiescent
astrocytes from rat cerebellum were stimulated to proliferate by mitogenic doses
of basic fibroblast growth factor (bFGF). Parallel to the bFGF mitogenic effect
was a marked, and persistent, decrease in cellular ceramide levels. Both in vitro
and in culture metabolic studies have led us to exclude both sphingomyelinase and
ceramidase involvement in ceramide level variation. Instead, we found evidence of
a functional connection between the decrease in ceramide levels and astrocyte
proliferation. In fact, cell growth in bFGF-stimulated astrocytes was inhibited
by exogenous ceramide and C2-ceramide, maximal inhibition being obtained at a
ceramide concentration of 5-10 microM. Under the same conditions, the
dihydroderivatives of ceramides were without effect. Following ceramide
treatment, the phosphorylation of the MAP kinase isoforms ERK1/2, key components
in bFGF-induced cell proliferation, was examined. The administration of
antiproliferative doses of ceramide or C2-ceramide, but not of their
dihydroderivatives, resulted in a significant inhibition of ERK1/2 activation. In
conclusion, our data indicate that the prompt modulation of ceramide levels by
bFGF is an early step associated with the signaling pathways responsible for the
mitogenic activity of bFGF in astrocytes.
PMID- 11008214
TI - Growth and migration markers of rat C6 glioma cells identified by serial analysis
of gene expression.
AB - Tumors derived from rat C6 cell implants into rat brain exhibit similar
morphological characteristics and degree of vascularization to human
glioblastomas. To establish a molecular basis for C6 gliosarcoma malignancy, we
have constructed a molecular profile of the most abundantly expressed genes,
using serial analysis of gene expression (SAGE). Sequence tags (1168)
representing 738 individual transcripts were collected and tag-to-gene mapping
was carried out using the UniGene data set for rat. Differentially expressed C6
transcripts were identified by comparison of tags collected for C6 cells with a
similar number (1002) of tags from a rat primary astrocyte library. Genes found
to be expressed at increased levels in C6 cells are associated with cell surface
interactions, migration, or metastasis formation and proliferation. These include
the receptor for hyaluronan-mediated motility (RHAMM), S-100 related protein 42A,
galectin I, preproenkephalin, osteopontin, autocrine motility factor, alpha
tubulin, ad1 antigen, and cofilin. In addition, a tag with no database match
probably representing a previously uncharacterized transcript was differentially
expressed in C6 cells. Transcripts showing reduced expression in C6 cells
relative to astrocytes included the extracellular matrix glycoprotein
osteonectin/SPARC (secreted protein, acidic, rich in cysteine), actin-binding
proteins thymosins beta-4 and beta-10, the cysteine protease inhibitor cystatin
C, the actin-gelling protein SM22/transgelin, and ferritin-H. SAGE results were
confirmed by Northern blot for all transcripts tested, reaffirming the value of
the SAGE technique for expression profiling in cancer biology.
PMID- 11008215
TI - Production of macrophage inflammatory protein-2 following hypoxia/reoxygenation
in glial cells.
AB - Polymorphonuclear neutrophils (PMNs) are known to mediate brain inflammation
following hypoxia/reoxygenation (H/R), but the precise mechanisms leading to PMN
recruitment are undefined. The alpha-chemokine macrophage inflammatory protein-2
(MIP-2) has specificity for the recruitment of PMNs. In this study, we found that
8 or 12 h of hypoxia followed by 24-h reoxygenation (H8/R24 or H12/R24) induced
MIP-2 secretion in cultures of enriched microglia or mixed glia, respectively.
Microglia, however, could not survive longer duration (>12 h) of hypoxia.
Astrocytes did not produce any significant amount of MIP-2 even though astrocytes
maintained 98-99% viability following H12/R24. We also found that microglia
survived the H/R treatment better (following H24) in the presence of astrocytes
(mixed glial culture) than in microglia-enriched culture. Reoxygenation for
prolonged periods (3 and 5 days) following H24 resulted in progressively larger
increases in MIP-2 production (20- and 60-fold, respectively) in mixed glial
cultures. Immunocytochemical staining revealed that the cells expressing MIP-2 in
response to H/R were microglia rather than astrocytes in mixed glial cultures.
Examination of MIP-2 mRNA expression showed that H/R upregulated MIP-2 gene
expression. Taken together, our data suggest that microglial cells are an
important source of MIP-2 production and suggest a potential injury mechanism
involving brain-derived production of MIP-2 in H/R.
PMID- 11008216
TI - Gene expression of the transporters and biosynthetic enzymes of the osmolytes in
astrocyte primary cultures exposed to hyperosmotic conditions.
AB - Sorbitol, myo-inositol, betaine, and taurine are held as organic osmolytes. When
cells are exposed to a hyperosmotic medium, they accumulate these organic
compounds and thus achieve osmotic equilibrium with the medium while maintaining
their volume. In astrocyte primary cultures adapted to a chemically defined
medium and then exposed to a medium made 30% hyperosmotic by adding sodium
chloride or raffinose, we have comparatively investigated the expression of the
genes encoding the proteins that control the cellular accumulation of these
osmolytes, namely sorbitol biosynthetic enzyme, aldose reductase (AR), taurine
biosynthetic enzymes, cysteine dioxygenase (CDO), and cysteine sulfinic acid
decarboxylase (CSD), and the transporters of taurine (TauT), myo-inositol (SMIT),
and betaine (BGT1) by assaying the corresponding mRNA levels through relative
quantitative RT-PCR. When exposed to the hyperosmotic medium the astrocytes
shrank rapidly and then slowly regained their initial volume after several hours.
CDO- and CSD-mRNA remained unchanged, whereas AR-mRNA appeared increased only
with the medium made hyperosmotic with sodium chloride. The mRNA levels of the
transporters only showed significant and comparable increases in both
hyperosmotic conditions. They were all significantly higher after 4-h exposure
and back or close to normal values after 24-h exposure. The maximum level
occurred at around 4 h (SMIT), 8 h (BGT1), and 12 h (TauT). The amplitude of BGT1
mRNA increase was much larger. When taurine was added to the hyperosmotic medium
the cell volume recovery was greatly accelerated and the osmo-induced
overexpression of TauT-, SMIT-, and BGT1-mRNA was fully prevented. The activation
of the genes encoding the osmolyte transporters appears to be triggered when the
cell shrinks below a certain volume threshold and prolonged once the cell volume
has regained this threshold value most likely as a result of a marked inertia of
the transducing pathway. Since the upregulation pattern of the transporters of
the different osmolytes notably differs, we speculate that the activation
threshold varies from one gene to another.
PMID- 11008217
TI - Subcommissural organ/Reissner's fiber complex: characterization of SCO-spondin, a
glycoprotein with potent activity on neurite outgrowth.
AB - In the developing vertebrate nervous system, several proteins of the
thrombospondin superfamily act on axonal pathfinding. By successive screening of
a SCO-cDNA library, we have characterized a new member of this superfamily, which
we call SCO-spondin. This extracellular matrix glycoprotein of 4,560 amino acids
is expressed and secreted early in development by the subcommissural organ (SCO),
an ependymal differentiation located in the roof of the Sylvian aqueduct.
Furthermore, SCO-spondin makes part of Reissner's fiber (RF), a thread-like
structure present in the central canal of the spinal cord. This novel protein
shows a unique arrangement of several conserved domains, including 26
thrombospondin type 1 repeats (TSR), nine low-density lipoprotein receptor (LDLr)
type A domains, two epidermal growth factor (EGF)-like domains, and N- and C
terminal von Willebrand factor (vWF) cysteine-rich domains, all of which are
potent sites of protein-protein interaction. Regarding the huge number of TSR,
the putative function of SCO-spondin on axonal guidance is discussed in
comparison with other developmental molecules of the CNS exhibiting TSR. To
correlate SCO-spondin molecular feature and function, we tested the effect of
oligopeptides, whose sequences include highly conserved amino acids of the
consensus domains on a neuroblastoma cell line B 104. One of these peptides
(WSGWSSCSRSCG) markedly increased neurite outgrowth of B 104 cells and this
effect was dose dependent. Thus, SCO-spondin is a favorable substrate for neurite
outgrowth and may participate in the posterior commissure formation and spinal
cord differentiation during ontogenesis of the central nervous system.
PMID- 11008218
TI - Targeted disruption of Muller cell metabolism induces photoreceptor
dysmorphogenesis.
AB - Within the retina, the Muller cells and photoreceptors are in close physical
proximity and are metabolically coupled. It is unknown, however, whether Muller
cells affect photoreceptor differentiation and outer segment membrane assembly.
The objective of this study was to determine whether targeted disruption of
Muller cell metabolism would induce photoreceptor dysmorphogenesis. Intact
isolated Xenopus laevis embryonic eyes were cultured in medium with or without
Muller cell-specific inhibitors (i.e., alpha-aminoadipic acid and fluorocitrate).
To assess Muller cell injury, the gross retinal morphology was examined along
with immunocytochemical assessment of Muller cell-specific protein expression
patterns. The steady-state levels of opsin were quantified to determine whether
the Muller cell inhibitors negatively affected photoreceptor protein synthesis.
Muller and photoreceptor cell ultrastructure was scrutinized and the organization
of the outer segment membranes was graded. In control retinas, there was no
swelling of Muller cell cytoplasm. Glial fibrillary acidic protein (GFAP) was
undetectable, whereas glutamine synthetase was abundant. The steady-state level
of opsin was high and photoreceptors elaborated properly folded outer segments.
Exposure to both Muller cell-specific inhibitors induced swelling of Muller cell
endfeet, cytoplasmic paling and alterations of Muller cell-specific protein
expression patterns. The steady-state level of opsin in retinas exposed to alpha
aminoadipic acid was unchanged compared with control eyes, whereas, in eyes
exposed to fluorocitrate, opsin levels were slightly reduced. The most
significant finding was that targeted disruption of Muller cell metabolism
adversely affected photoreceptor outer segment membrane assembly, causing
dysmorphogenesis of nascent outer segments. These results suggest that the
termination signal(s) necessary for proper outer segment folding were disrupted
by targeted inhibition of Muller cells and support the hypothesis that Muller
cells interact with photoreceptors through mechanisms that may regulate, at least
in part, the assembly of photoreceptor outer segment membranes.
PMID- 11008219
TI - Epidemiology of nosocomial candidiasis: the importance of molecular typing.
AB - Modern epidemiology studies now require that nosocomial pathogens be
characterized to the subspecies level whenever possible to better define
infectious processes and modes of transmission. In general, if isolates are
classified as different by at least one molecular typing method, they may be
assumed to represent different strains and to reflect independent infections. If
the isolates are the same, it may be assumed that cross infection has occurred or
that the patients were infected by exposure to a common source. Typing methods
may also be used to address clinical problems related to distinguishing
reinfection versus relapse of an infection, and to examine the development of
antifungal resistance among fungal pathogens during the course of antifungal
therapy. Determining DNA fingerprints of sequential isolates from patients
undergoing antifungal therapy has been useful in demonstrating the potential for
the development of antifungal resistance in previously susceptible strains and
for detecting the substitution of a more resistant strain for a more susceptible
strain in the face of intense antimicrobial pressure. In order to be useful as an
epidemiological typing method, a DNA fingerprinting system must effectively
distinguish between genetically unrelated strains, identify the same strain in
separate samples, and reflect genetic relatedness or unrelatedness (genetic
distance) among strains.
PMID- 11008220
TI - Candiduria in hospitalized patients: a review.
AB - The presence of Candida species in the urine is frequent among hospitalized
patients. It represents a major challenge to the physician because it is unclear
whether candiduria represents colonization or infection, whether the bladder or
the kidney is involved in infection, or whether it represents a surrogate marker
for systemic infection. This picture is more complicated because there are few
prospective studies addressing the issue of when and how to treat a patient with
candiduria. Strategies for management are based on the presence or absence of
other features such as anatomic genitourinary abnormalities, renal transplant,
and fever. If treatment is considered, fluconazole is the drug of choice,
provided the agent is not Candida krusei or Candida glabrata.
PMID- 11008221
TI - Assessing efficacy by measuring CD(4) counts and quality of life of AIDS patients
treated with ritonavir, AZT and 3TC.
AB - Lamivudine and zidovudine are proving to be an important antiretroviral
combination against HIV that is superior to monotherapy. Recently, with the
appearance of protease inhibitors, ritonavir has been shown to be a powerful drug
when used in combination with reverse transcriptase inhibitors. The objective of
this study was to observe the efficacy, adverse events, and changes in the
quality of life of AIDS patients receiving treatment for the first time using
AZT, 3TC and ritonavir as combination therapy. We selected 36 patients diagnosed
with AIDS due to opportunistic infections and evaluated them by assessing their
score on quality of life scales (Karnofsky, uniscale - Quality of Life, and
Quality of Life Scale), T CD(4) and CD(8) lymphocyte counts, bodyweight and
symptoms during a 6 month period. Assessments were made at 2 month intervals. One
patient was excluded from the trial, therefore, 35 were assessed during 6 months.
RESULTS: Bodyweight increased an average of 7.2%, CD(4) increased 260 cells/mm(3)
and CD(8) increased 198 cells/mm(3). The Karnofsky and uniscale QOL scales
reached 100% on the fourth visit. The Quality of Life Scale showed an important
increase during this study from 5.5+/-2.3 to 9.7+/-0.5. Adverse events were
observed in 25.0% of the patients, most being slight. One patient had to stop
taking ritonavir due to nausea and vomiting. We conclude that AZT, 3TC, and
ritonavir restored the quality of life for the AIDS patients studied in terms of
psychosocial aspects and overall health conditions during 6 months of treatment.
The adverse events were probably related to ritonavir, but they were slight and
disappeared after 2 weeks. There was a significant increase in the average number
of CD(4) lymphocytes during 6 months of treatment.
PMID- 11008222
TI - A prospective and randomized study using ribavirin as monotherapy for the
treatment of naive patients with chronic hepatitis C.
AB - In order to evaluate the response to ribavirin in previously untreated patients
with chronic hepatitic C, 39 patients were selected for a double-blind
prospective and randomized trial, and divided into two groups: ribavirin-group
(19 patients) and placebo-group (20 patients). Ribavirin was administered orally
for 24 weeks (600 mg/day, followed by 1,000 mg/day and 1,200 mg/day each one for
8 weeks). After 3 months of drug administration, the patients were evaluated by
measuring biochemical, virologic and histologic responses. After this phase,
ribavirin was offered to the patients who had received placebo (second phase).
The results showed that the patients who received ribavirin showed a higher
reduction in serum alanine aminotransferase (ALT) activity than patients in the
placebo group. Among the patients in the ribavirin-group, a complete biochemical
response (ALT levels normalized) was observed in 3 patients (16%), and a partial
response (reduction greater than 50% of the initial value of ALT activity) in 4
(21%). In the 20 patients in the placebo group, only 1 showed a partial response
(5%). In the second phase of the study, among 16 patients who received ribavirin,
4 (25%) showed a complete and 5 (31%) a partial biochemical response. HCV-RNA did
not become negative in any patient during the two phases. A reduction in the
score of portal and lobular activity was observed in patients who received
ribavirin, but statistical analysis did not identify differences. This study
showed that ribavirin alone induces a biochemical response (ALT reduction) in
some patients with chronic hepatitis C, which may be associated with a reduction
in hepatic inflammatory activity reduction, but the changes are not sufficient to
recommend initial monotherapy with ribavirin.
PMID- 11008223
TI - Hepatitis B and hepatitis C prevalence among blood donors and HIV-1 infected
patients in Florianopolis--Brazil.
AB - Information is scarce on the prevalence of hepatitis B (HBV) and hepatitis C
(HCV) among voluntary blood donors and patients infected with the human
immunodeficiency virus (HIV) in Florianopolis, Brazil. A total of 2,678 serum
samples from 2,583 blood donors and 95 HIV-infected patients, collected between
April, 1994, and March, 1995, were examined for markers of HBV and HCV. All the
samples were analyzed to detect HBV and HCV markers (HBsAg, anti-HBc, and anti
HCV). Hepatitis B and C prevalence among the studied blood donors reached 9.3%
and 1.0%, respectively; 0.7% being seropositive for HBsAg and 9.2% for anti-HBc.
It was also verified that 0.1% of blood donors were seropositive for HBsAg alone,
8.6% seropositive for the anti-HBc alone, and 0.6% presented a positive reaction
for both of the HBV markers studied. Among HIV-infected patients, prevalence of
69.5% and 54.7% for hepatitis B and hepatitis C, respectively, were observed. Of
these patients, 18.9% were seropositive for HBsAg, and 66.3% for the anti-HBc.
The prevalence of a reaction for HBsAg alone, and for anti-HBc alone was 3.1% and
50.5%, respectively, for HIV-infected patients, whereas 15.8% were seropositive
for both of the studied markers. HBV and HCV coinfection was 0.1% in blood
donors, and 40% of those patients tested seropositive for HIV. Results show
prevalence of HBV and HCV infection to be significantly greater among HIV
infected patients than among blood donors. These observations confirm the high
frequency of HIV-infected patients exposure to these other viruses.
PMID- 11008224
TI - Tissue pharmacokinetics of amoxicillin. An experimental design in rats.
AB - Amoxicillin is used as the drug of first choice in many situations in medicine
and dentistry, in spite of several reports regarding bacterial resistance. There
is little data about the tissue concentration of this antimicrobial agent. Serum
levels of amoxicillin have been evaluated in detail, but tissue levels have not.
This study was carried out to determine the tissue concentration of amoxicillin
during the first 10 h after administration. Four polyurethane sponges were
implanted in the backs of 54 male rats. After 14 days, they received 40 mg/kg of
po amoxicillin suspension. The animals were killed in groups of 6 at 15, 30, 60,
90, 120, 240, 360, 480 and 600 min after the administration. Serum, placed on
paper discs, and granulomatous tissue were assayed by a microbiological method
using Mueller Hinton agar inoculated with 108 cfu of Staphylococcus aureus (ATCC
25923). After 18 h of incubation, the inhibition zones were measured. It was
observed that the drug in the serum and the tissue reached higher concentrations
than MIC and MBC within a period of 30 min and 8 h following administration. We
conclude that this method can allow determination of antibiotic tissue
concentration without the need for infecting the animal and, therefore, without
the associated animal pain and suffering in presently used models.
PMID- 11008225
TI - Kikuchi's disease: report of 2 cases and a brief review of the literature.
AB - Kikuchi's lymphadenitis is a histiocytic necrotizing lymphadenitis without
granulocytic infiltration, with fever and generally with a benign course, despite
its pathologic resemblance to malignant lymphoma. The illness usually begins with
localized cervical adenopathy in young adult females, predominantly before the
fourth decade of life. Clinically, several agents could be the cause of such an
illness--toxoplasmosis, herpes group viral infection, cat scratch disease,
lymphoma, SLE and other infectious agents. The diagnosis is made by using a
histological technique. The lymph node biopsy reveals fibrinoid necrosis, loss of
lymph node structure with many histiocytes and an absence of granulomatous
reaction. The immunohistochemical analysis shows that the main affected cellular
components are the T cells. Laboratory exams show an erythrocyte sedimentation
increase, neutropenia, leukopenia and lymphocytosis. We describe two cases that
were followed since 1994 and 1996, respectively. Both were females under 25 years
old, who developed a febrile disease with lymphadenopathy. Lymph node biopsies
showed necrotizing lymphadenitis without granulocytic infiltrations. The patients
had no evidence of other systemic diseases. Our objectives are to present a rare
cause of febrile disease with enlargement of cervical lymph nodes, to review
Kikuchi's disease, and to alert the medical community to this rare cause of fever
and lymphadenopathy.
PMID- 11008226
TI - Publication of presentations made at The Brazilian Congress of Infectious
Diseases: a note of appreciation to the authors.
PMID- 11008228
TI - Commentary on 'Colorectal Cancer' by rodriguez-bigas et al
PMID- 11008227
TI - Colorectal cancer: how does it start? How does it metastasize?
AB - Colorectal carcinogenesis is a multistep process with an apparently orderly
progression from benign tissue to invasive malignancy and metastases. Yet at the
genome level, a considerably more chaotic situation exists, with order arising
through the process of natural selection in the midst of genomic instability.
Major pathways for colorectal carcinogenesis begin with suppressor loss or
acquisition of a mutator phenotype, but there are other pathways known and yet to
be described. These pathways result in the natural selection of cells with
unstable genomes leading to malignancy and metastases.
PMID- 11008230
TI - Commentary on 'Primary Prevention' by friedlich and stern
PMID- 11008229
TI - Primary prevention: what can you tell your patient?
AB - Colorectal cancer, with its high incidence and significant morbidity and
mortality, remains one of the leading causes of cancer-related deaths worldwide.
Primary prevention of colorectal cancer may be more cost-effective and practical
than secondary prevention. The primary prevention of colorectal cancer involves
dietary and environmental modifications, chemoprevention, and in some cases
prophylactic surgery.
PMID- 11008231
TI - Average-risk screening: is public policy compatible with individual needs?
AB - The issue of the appropriateness of population-based screening for colorectal
cancer has been much debated in the literature. The purpose of screening is to
find early-stage disease among average-risk members of the population so that
timely treatment may be implemented and mortality reduced. The goal of public
policies regarding screening should be to facilitate this result. The adequacy of
current public policy for reduction of colorectal cancer mortality is the main
focus of this article.
PMID- 11008232
TI - Commentary on 'Average-risk Screening' by levin and hawley
PMID- 11008234
TI - Commentary on 'Familial adenomatous polyposis, hereditary nonpolyposis colon
cancer, and familial Risk' by thorson and faria
PMID- 11008233
TI - Familial adenomatous polyposis, hereditary nonpolyposis colon cancer, and
familial risk: what are the implications for the surgeon?
AB - Recent advances in the understanding of the molecular biology of colorectal
cancer have resulted in many new implications for surgeons. To continue providing
sound patient care, surgeons must familiarize themselves with associated issues
that include genetic counseling and its role in patient and family management.
Issues related to genetic counseling are reviewed in this article.
Recommendations for surgical therapy and surveillance methods are summarized for
each of the hereditary syndromes. Failure to use these patient management tools
in an effective way may be a source of future litigation.
PMID- 11008235
TI - Staging: what makes sense? Can the pathologist help?
AB - The staging of colorectal cancer continues to be an interesting and evolving
process. Accurate staging can predict overall prognosis and helps to select
appropriate treatment options. This article addresses the clinical and pathologic
staging of colon and rectal cancer. The use of endorectal ultrasound in the
preoperative clinical staging of rectal cancer is reviewed. The importance of
surgical resection margins, lymph node retrieval rates, and tumor markers is
discussed.
PMID- 11008236
TI - Commentary on 'Staging' by bernick and wong
PMID- 11008238
TI - Commentary on 'Current protocols and outcomes for colonic Cancer' by guleserian
and bland
PMID- 11008237
TI - Current protocols and outcomes for colonic cancer: why do we fail?
AB - As the second leading cause of cancer-related deaths, colorectal cancer remains a
significant health problem for American men and women. Advances in diagnosis,
screening, surgical techniques, and adjuvant therapy have improved survival over
the past 30 years. Although most novel therapies are in early stages of
development, they offer potential for major advances in the management of
colorectal cancer. Continued efforts focused on disease prevention, along with a
better understanding of the tumor biology, cancer immunotherapy, and gene therapy
will certainly yield more sophisticated and effective treatment strategies for
all patients who are either at risk for or have already been diagnosed with
colorectal cancer. As increasing numbers of clinicians, scientists, and health
care professionals continue to address these issues, better interventions and
therapies are likely to emerge.
PMID- 11008240
TI - Commentary on 'Radical surgery for rectal Cancer' by cohen
PMID- 11008239
TI - Radical surgery for rectal cancer: why we fail and rationale for current clinical
trials of adjuvant therapy.
AB - The major goals in the treatment of patients with rectal cancer are overall cure,
maximizing local control, and maintaining quality of life. Quality of life issues
include avoidance of a permanent stoma and maintaining adequate bowel, sexual,
and urinary function. Optimizing the surgical technique with a more selective
application of adjuvant therapy will meet these goals. This article describes the
likely explanations for local and distant recurrence and delineates current
clinical trials of adjuvant therapy directed toward minimizing failure despite
potentially curative surgical resection.
PMID- 11008241
TI - Current protocols and outcomes of local therapy for rectal cancer.
AB - Rectal cancer is a devastating disease, with patients fearing the disease and the
potential treatments that may alter sexual function, genitourinary function, and
overall body image. Defining the precise role for less morbid approaches to this
disease, such as local excision, is of critical importance in providing optimal
care in the future. This article discusses endocavitary radiation and
fulguration, local excision, and prospective studies.
PMID- 11008242
TI - Commentary on 'Current protocols and outcomes of local therapy for rectal Cancer'
by bleday and steele
PMID- 11008244
TI - Commentary on 'Laparoscopic resection for colorectal Cancer' by lee et al
PMID- 11008243
TI - Laparoscopic resection for colorectal cancer: is it justified?
AB - Controversy remains regarding the appropriateness of laparoscopic methods for the
curative resection of colonic neoplasms. Long-term results after minimally
invasive resection must be shown to be equivalent or better than those after open
resection in order to justify the new technique in the setting of cancer. This
article discusses adequacy of resection and short-term results, long-term outcome
data, port and abdominal wound tumors, oncologic and immunologic basic science
data, and the role of laparoscopy in the treatment of rectal cancers.
PMID- 11008245
TI - Operative techniques for radical surgery for rectal carcinoma: can surgeons
improve outcomes?
AB - Local recurrence rates following resection of rectal cancer with curative intent
are extremely variable. An appropriate anatomic dissection of the rectum is
essential to accomplish a complete removal of the tumor and has been described
since the 1940s. In the last two decades, increased emphasis has been placed on
the concept of total mesorectal excision as the fundamental technical step to
minimize local recurrence rates. It is currently accepted, however, that complete
removal of the mesorectum is not necessary for all rectal cancer cases. On the
other hand, measurement of the free radial margins should be routinely performed
to evaluate the local aggressiveness of the disease and assess the potential for
a curative resection.
PMID- 11008246
TI - Commentary on 'Operative techniques for radical surgery for rectal Carcinoma' by
stocchi and wolff
PMID- 11008248
TI - Commentary on 'Rectal cancer adjuvant therapy Controversies' by rakinic and Fry
PMID- 11008247
TI - Rectal cancer adjuvant therapy controversies: When? What? Why?
AB - Although the need for adjuvant therapy in high-risk rectal cancer is widely
accepted, controversies continue regarding timing, mode, and agents employed. The
current recommended practice and its scientific basis are reviewed. Studies of
induction therapy are discussed. Evidence of efficacy of new anticancer agents
and modes of drug delivery are presented.
PMID- 11008249
TI - New adjuvant therapy for colon cancer: justified hope or commercial hype.
AB - This article discusses the role of adjuvant chemotherapy for colon cancer. Six
months of adjuvant 5-FU/leucovorin represent the standard of care for resected
stage III colon cancer patients. The role of adjuvant chemotherapy for stage II
patients remains controversial. Future directions in the adjuvant treatment of
colon cancer include incorporation of newer agents such as irinotecan,
oxaliplatin, oral fluorinated pyrimidines, and immunotherapeutic approaches.
PMID- 11008250
TI - Commentary on 'New adjuvant therapy for colon Cancer' by galanis et al
PMID- 11008251
TI - Follow-up: does it work? Can we afford it?
AB - Follow-up of patients with colorectal cancer has been controversial. This is
largely because studies have been small and inadequate to assess results. A
recently performed meta-analysis confirms a very significant benefit to the
follow-up of patients following curative resection of colorectal cancer. This
article outlines the rationale and cost-effectiveness of a follow-up policy.
PMID- 11008252
TI - Commentary on 'Follow-Up' by beart
PMID- 11008253
TI - Decision-making: what tests to do? What choices to consider?
AB - The treatment of recurrent colorectal cancer confronts the surgeon with a
diagnostic and therapeutic challenge, particularly in cases involving the pelvis.
Investigation and treatment in each case is tailored to the individual patient.
Treatment is divided into those cases where an attempt at cure is possible and
those where only palliation of symptoms is possible. This article seeks to help
the surgeon confronted with this problem answer the following questions: Which
patients with recurrent colorectal cancer are suitable for consideration of
curative resection? What is the extent of disease recurrence? Is the disease
resectable? The aim of this article is to offer advice in the logical and
appropriate investigation and treatment of patients considered for curative or
palliative therapy.
PMID- 11008254
TI - Commentary on 'Decision-Making' by fazio and harris
PMID- 11008255
TI - Current management of colorectal liver metastases.
AB - Colorectal cancer metastatic to the liver represents an uncommon situation in
surgical oncology in which metastasectomy can effect longevity and may lead to
cure. Liver resection can be done safely and has drastically improved 5-year
survival rates to upwards of 35%, but only a minority of patients is eligible.
Advances in imaging techniques facilitate detection of metastases and improve
patient selection. For unresectable patients, and as an adjunct to resection,
local disease control may be achieved with cryosurgery, radiofrequency ablation,
or regional chemotherapy delivered by way of infusion through the hepatic artery.
Areas of ongoing investigation include regional gene therapy and interference
with tumor growth by inhibition of angiogenesis.
PMID- 11008256
TI - Commentary on 'Current management of colorectal liver Metastases' by martin and
warren
PMID- 11008257
TI - Pontocerebellar hypoplasia--how many types?
AB - An original article describes a sibship with early fatal pontocerebellar
hypoplasia of a yet unclassified type, with the accompanying features of
polyhydramnios and neonatal myoclonus. Autopsy in one patient excluded spinal
anterior horn involvement, which argues against pontocerebellar hypoplasia type I
(PCH-1). The present PCH classification and literature are briefly reviewed. Four
previous publications bear similarity to the present report. Definite
classification as a genetically separate entity, however, remains elusive pending
localization and identification of the gene(s) involved.
PMID- 11008258
TI - What's new in congenital disorders of glycosylation?
PMID- 11008259
TI - Provocation of non-convulsive status epilepticus by tiagabine in three adolescent
patients.
AB - Three girls, two aged 12 years and one aged 17 years with refractory localization
related epilepsy were treated on an add-on basis with tiagabine. At dosages 22.5
30 mg/day (0.45-0.57 mg/kg/day) longstanding non-convulsive status epilepticus
was noted in all three patients. The events of non-convulsive status epilepticus
subsided following reduction in tiagabine dosages. In two cases, tiagabine was
withdrawn, whereas it was continued at a lower dosage in one case. This is the
first report of non-convulsive status epilepticus provoked by tiagabine in
adolescent patients.
PMID- 11008260
TI - Early fatal pontocerebellar hypoplasia in premature twin sisters.
AB - We report clinical, neuroradiological and neuropathological findings of
monozygotic twin sisters born at 30 weeks' gestation, with pontocerebellar
hypoplasia (PCH) similar but not identical to type 2 PCH. They presented with
hypertonia, jitteriness, spontaneous and provoked myoclonic jerks
(hyperekplexia), apnoeic episodes, and progressive microcephaly. They died at 7
weeks of age from respiratory failure.
PMID- 11008261
TI - Retinitis and dementia in a pregnant girl: an unusual case.
AB - A 14-year-old pregnant Caucasian girl presented with a 1-week history of
dementia. She had presented 1 year prior with acute unilateral visual impairment
and was noted to have macular degeneration of presumed infective aetiology. This
evolved to a pigmentary macular lesion. During the course of the current
presentation she developed myoclonic jerks. An electroencephalogram revealed
periodic spike and slow wave complexes at 1-2 second intervals. Blood and
cerebrospinal fluid examination showed raised anti-measles IgG antibody titres.
Intrathecal synthesis of anti-measles virus antibody was demonstrated
unequivocally and a diagnosis of subacute sclerosing panencephalitis was made. A
healthy male infant was delivered by elective caesarean section at 33 weeks'
gestation. She continued to deteriorate clinically despite treatment with
intraventricular alpha-interferon. She had not had primary immunization against
measles.
PMID- 11008262
TI - Mesenteric angina complicating a mesodermal anomaly.
AB - A child with macrocephaly-cutis marmorata developed severe abdominal pain thought
to represent mesenteric angina. There were abnormalities of the aortic and
mesenteric vasculature not previously reported in this condition. Angina therapy
afforded amelioration of his symptoms. Mesenteric angina should be considered as
a cause for abdominal pain in children with mesodermal anomalies.
PMID- 11008263
TI - Moyamoya syndrome with protein S deficiency.
AB - Moyamoya disease is a cerebrovascular disease with progressive occlusion of both
internal carotid arteries and of their branches and formation of a new vascular
network at the base of the brain. Because of the angiographic appearance, it is
named as moyamoya. The clinical features are cerebral ischaemia, recurrent
transient ischaemic attacks, sensorimotor paralysis, convulsions and migraine
like headaches. A 10-year-old child who acutely developed hemiparesis, weakness
and aphasia was found to have moyamoya disease and heterozygous protein S
deficiency. This case shows us that during the thromboembolic events the
coexistence of protein S deficiency and moyamoya should be investigated.
PMID- 11008265
TI - Forthcoming meetings
PMID- 11008264
TI - Septo-optic dysplasia in combination with a pigmented skin lesion: a case report
with nosological discussion.
AB - In this case report a patient with bilateral optic nerve hypoplasia,
schizencephaly and a pigmented skin lesion is described. The diagnosis of de
Morsier syndrome or septo-optic dysplasia is put forward on the basis of the
diagnosis of optic nerve hypoplasia. The differential diagnosis with Jadassohn's
naevus phakomatosis is discussed. The importance of direct ophthalmoscopy of
optic nerve abnormalities is stressed, as well as of magnetic resonance imaging,
which has become a guideline in the classification of this syndrome.
PMID- 11008266
TI - Advantages of rhythmic movements at resonance: minimal active degrees of freedom,
minimal noise, and maximal predictability.
AB - Using time delay embedding, the authors applied phase space reconstruction to the
time series of rhythmic movements of a hand-held pendulum. Subjects (N = 6)
produced the manual oscillations about the wrist at the pendulum's resonant
frequency and at a higher and a lower frequency. The number of active degrees of
freedom required to capture the dynamics of the rhythmic behavior was 3 for the
resonant frequency and 4 for each of the nonresonant frequencies. The residual
high-dimensional noise was similarly lowest for the resonant frequency. Whereas
33% and 20%, respectively, of the vectors in the phase spaces of the dynamics
higher and lower than resonance were unpredictable, only 12% were unpredictable
at resonance. Finally, the predictability of the evolving dynamics extended
farther into the future for oscillations at the resonant frequency. At resonance,
the prediction horizon was 5 times farther than the prediction horizon for the
higher than resonance behavior and 2.5 times farther than that for the lower than
resonance behavior. The results suggest that, in pendular oscillations of a limb
or limb segment, attunement of the central nervous system to the resonant
frequency minimizes the variables to be controlled and maximizes the
predictability of the rhythmic movement's chaotic dynamics.
PMID- 11008267
TI - Changes in movement symmetry associated with strengthening and fatigue of agonist
and antagonist muscles.
AB - The hypothesis that strengthening or fatiguing procedures applied on active
muscles can affect the symmetry of rapid, discrete movements was tested. Subjects
(N = 12) performed rapid, consecutive elbow flexions and extensions between 2
targets before and after (a) applying a strength training program, (b) fatiguing
elbow flexors, and (c) fatiguing elbow extensors. The results demonstrated that
an increase in strength of elbow extensors caused by applied strength training is
associated with an increase in the symmetry ratio (i.e., acceleration time
divided by deceleration time) of elbow flexion movements. The symmetry ratio also
increased and decreased in movements when agonists and antagonists were fatigued,
respectively. Because the strength training and fatiguing procedures are both
known to affect muscle force, the data are interpreted as changes in muscles'
ability to exert the force while acting as agonists or antagonists. Namely,
muscles need equal impulses of force (torque multiplied by time) to accelerate
and, thereafter, to decelerate the limb while performing a rapid, discrete
movement. The symmetry ratio may therefore be changed so that more time will be
provided for muscles that become relatively weaker (compared with their
antagonists) because a strengthening or fatiguing procedure has been applied,
whereas a shorter time period should be sufficient for action of their stronger
antagonists. Although, in the literature, the studied phenomenon has been
discussed as a predominantly motor control phenomenon, the present data suggest
that the movement symmetry could also be related to agonists' and antagonists'
ability to exert force, particularly while performing rapid, discrete movements.
PMID- 11008268
TI - Visual dominance in amending the directional parameter of feedforward control.
AB - The authors examined visual dominance between trials in which the movement
program was amended (i.e., off-line processing). Weighting between visual and
proprioceptive feedback was examined in a trial-by-trial analysis of the
directional parameter of feedforward control. Eight participants moved a cursor
to a target displayed on a computer screen by manipulating a hand-held stylus on
a digitizing tablet. In the first 30 trials, the cursor followed the stylus
movement (practice condition). In the next 30 trials, the directional error of
the stylus movement was presented in the opposite direction (reversal condition).
Subjects knew the presence and the nature of the reversal. In the last 10 trials,
the reversal was withdrawn (transfer condition). Directional error of feedforward
control was relatively small in the practice condition, and it increased
gradually in 1 of 2 directions as trials proceeded in the reversal condition.
Positive aftereffect was observed in the transfer condition. A constant increment
of the directional error indicated that both visual and proprioceptive feedback
are registered, with higher weight on vision, and that weighting between those
inputs is determined automatically or is fixed without any strategic control.
PMID- 11008269
TI - Physical and observational practice afford unique learning opportunities.
AB - In 2 experiments, the authors studied the effectiveness of physical and
observational practice on learning and the effect on learning of combining
physical practice and observation, as compared with providing physical practice
alone. In Experiment 1, retention and transfer performance of 30 university
students after physical, observational, or no practice were contrasted.
Consistent with findings from other studies, the retention results indicated that
observational practice is inferior to physical practice. The transfer data
indicated no differences between observation and physical practice groups. In
Experiment 2, retention and transfer performance of 30 participants in physical
and combined (alternating physical and observational) practice groups were
contrasted. The retention results showed no differences between the combined and
physical practice groups, but the combined group performed significantly better
than the physical practice group on the transfer test. Those findings suggest
that a combination of observation and physical practice permits unique
opportunities for learning beyond those available via either practice regimen
alone.
PMID- 11008270
TI - A perception-action coupling type of control in long jumping.
AB - The authors' goal was to identify the control mechanisms used by long jumpers (N
= 6) to precisely position their foot at the board. In addition to the intertrial
method usually used in previous research, an original method based on a trial-by
trial analysis was also implemented. If the approach to the board in long jumping
encompasses two distinct sequences separated by a key step that marks the
initiation of visual control, then a trial-by-trial analysis should reveal those
sequences, regardless of the amount of adjustment: The step number at which
regulation is initiated should be the same irrespective of the amount of
adjustment. If, in contrast, a perception-action coupling mechanism operates,
then the step number at which regulation is initiated should be a function of the
amount of adjustment: A linear relation between those 2 variables should emerge.
The results of the present study are compatible with continuous control
mechanisms based on a perception-action coupling.
PMID- 11008271
TI - Effect of sex and joystick experience on pursuit tracking in adults.
AB - Using a joystick, adults (n = 39 males, 40 females in Experiment 1; n = 35 males,
40 females in Experiment 2; and n = 18 males, 18 females in Experiment 3)
performed a computerized pursuit tracking task. Contrary to previously reported
findings, the males were not more accurate than the females when performance was
adjusted for prior perceptual-motor experience. Although no sex differences were
found in a speeded tracking task, in an inverted tracking task the males
exhibited a significant performance advantage; that advantage remained after
several blocks of practice. Because participants' performance was adjusted
statistically for prior perceptual-motor experience, the male advantage in
inverted tracking was not related to experience. Rather, more proficient inverted
tracking performance was associated with higher 3-dimensional mental rotations
scores. In sum, sex differences in normal pursuit tracking may be better
explained by differences in perceptual-motor experience. Inverted tracking,
however, may depend on proficiency with spatial transformations.
PMID- 11008272
TI - Bernstein's theory of movement behavior: historical development and contemporary
relevance.
AB - In present-day movement science, N. A. Bernstein's formulation of the problems of
motor control is often taken as the starting point. The reliance on Bernstein has
not brought agreement among his followers, however. In this article, the authors
pose the following question: Does the disagreement arise from the structure of
his work itself or from incomplete exploitation of his thinking? By using, inter
alia, Bernstein's 24 English and German articles, the authors present an analysis
of the development of Bernstein's theory of movement behavior, against the
backdrop of the scientific progress in the Soviet Union in Bernstein's time and
the clashes between Soviet politics and science. Bernstein addressed in his early
articles the measurement and biomechanical analysis of movements. His
experimental data soon indicated the need for a new understanding of the
organization of movements, which he formulated in terms of coordination. Because
of political problems, his work was interrupted; but after being "rehabilitated"
and again allowed to work, Bernstein aimed to explain how animals find and
optimize the solutions to motor problems. The structure of the theory that ensued
was comprehensive exactly by virtue of his repeatedly shifting focus between the
different aspects of the organization of movement: More important than the
answers he gave were the questions he asked. Moreover, the way he approached
those questions may help scientists solve pressing problems in present-day
movement science.
PMID- 11008273
TI - Coordination of grip configurations as a function of force output.
AB - In this investigation, the authors examined the coordination and control of force
production by the digits of the hand as a function of criterion force level and
grip configuration. Each adult participant (N = 6: 3 men and 3 women) was
required to place the thumb and a finger (or fingers) upon load cells that were
fixed to a grasping apparatus that was clamped to a table. In the task,
participants had to match a criterion continuous constant total force level
displayed on a computer screen. There were 10 trials at each grip configuration
and criterion force level combination on each of 3 consecutive days. The results
showed that (a) different grip configurations minimized error at each force
level; (b) there was a specific digit pairing within a given grip configuration
that produced the highest correlation of force output; (c) the correlation
between the force output of digits generally increased at higher force levels;
(d) error was reduced at each force level and grip configuration over the
practice period; and (e) the organization of the force output of each digit
varied as a function of digit, force level, grip configuration, and practice. The
findings are consistent with the hypothesis that coordination of the digits in
prehension is reflective of an adaptive, task-specific solution that is modified
with practice.
PMID- 11008274
TI - Prism exposure aftereffects and direct effects for different movement and
feedback times.
AB - The effects of movement time and time to visual feedback (feedback time) on prism
exposure aftereffects and direct effects were studied. In Experiment 1, the
participants' (N = 60) pointing limb became visible early in the movement (.2-s
feedback time), and eye-head aftereffects increased with increasing movement time
(.5 to 3.0 s), but larger hand-head aftereffects showed little change. Direct
effects (terminal error during exposure) showed near-perfect compensation for the
prismatic displacement (11.4 diopters) when movement time was short but
decreasing compensation with longer movement times. In Experiment 2,
participants' (N = 48) eye-head aftereffects increased and their larger hand-head
aftereffects decreased with increasing movement time (2.0 and 3.0 s), especially
when feedback time increased (.25 and 1.5 s). Direct effects showed increasing
overcompensation for longer movement and feedback times. Those results suggest
that aftereffects and direct effects measure distinct adaptive processes, namely,
spatial realignment and strategic control, respectively. Differences in movement
and feedback times evoke different eye-hand coordination strategies and
consequent direct effects. Realignment aftereffects also depend upon the
coordination strategy deployed, but not all strategies support realignment.
Moreover, realignment is transparent to strategic control and, when added to
strategic correction, may produce nonadaptive performance.
PMID- 11008275
TI - The development of compensatory stepping skills in children.
AB - The development of the ability to use the step for balance recovery was studied
among twenty-five 9- to 19-month-old children. The children were grouped
according to walking experience (4 levels) and exposed to backward support
surface translations, 8 cm in amplitude, under 3 velocity conditions: 15, 20, and
25 cm/s. New walkers (up to 2 weeks' walking experience) used the step
infrequently and ineffectively in response to threats to balance. Intermediate
walkers (1-3 months' walking experience) showed an increasing use of the step and
significant improvement in step execution compared with new walkers. Advanced
walkers (>3; months' walking experience) experienced no falls throughout the
protocol, capturing balance with feet-in-place or step responses under all
perturbation conditions. A significant developmental transition in the emergence
of the compensatory step occurred between the new walker and the intermediate
walker experience levels, that is, within the first 3 months of walking
experience. Three to 6 months' experience was required for the development of an
effective stepping response. A concomitant change in mediolateral stability
paralleled the emergence of compensatory stepping.
PMID- 11008276
TI - [Effect strength variation in the single group pre-post study design: a critical
review].
AB - In Germany, studies in rehabilitation research--in particular evaluation studies
and examinations of quality of outcome--have so far mostly been executed
according to the uncontrolled one-group pre-post design. Assessment of outcome is
usually made by comparing the pre- and post-treatment means of the outcome
variables. The pre-post differences are checked, and in case of significance, the
results are increasingly presented in form of effect sizes. For this reason, this
contribution presents different effect size indices used for the one-group pre
post design--in spite of fundamental doubts which exist in relation to that
design due to its limited internal validity. The numerator concerning all effect
size indices of the one-group pre-post design is defined as difference between
the pre- and post-treatment means, whereas there are different possibilities and
recommendations with regard to the denominator and hence the standard deviation
that serves as the basis for standardizing the difference of the means. Used
above all are standardization oriented towards the standard deviation of the pre
treatment scores, standardization oriented towards the pooled standard deviation
of the pre- and post-treatment scores, and standardization oriented towards the
standard deviation of the pre-post differences. Two examples are given to
demonstrate that the different modes of calculating effect size indices in the
one-group pre-post design may lead to very different outcome patterns.
Additionally, it is pointed out that effect sizes from the uncontrolled one-group
pre-post design generally tend to be higher than effect sizes from studies
conducted with control groups. Finally, the pros and cons of the different effect
size indices are discussed and recommendations are given.
PMID- 11008277
TI - [Clinical studies in rehabilitation research--problems and solutions from
biometrical perspective].
AB - Methodology of clinical studies is highly sophisticated in drug research. But
clinical trials are also necessary to demonstrate efficacy and safety of
rehabilitation treatment. The call for evidence based medicine has also reached
rehabilitation. However, in rehabilitation medicine it is much more difficult to
design and conduct clinical trials with a high methodological standard. Among the
reasons are: A comparable control group is necessary because spontaneous healing
and unspecific measures contribute to therapeutic success, too. But what could
"placebo rehabilitation" look like? The masking of therapies (blinded studies)
will hardly ever be possible. Therefore, it is more difficult to achieve the same
treatment and observation for the treatment and control group. Treatments in
rehabilitation take longer to become effective than a drug and maybe the success
will disappear after some time. Therefore, long-term trials and follow-ups are
necessary. Such studies are expensive, need a strong organisation, and drop-outs
are unavoidable. An appropriate outcome variable does not always exist. "Return
to work" is an important, reliable and valid variable, but it delivers only one
bit of information per patient. As a consequence, smaller progress in
rehabilitation can only be demonstrated with large sample sizes. Outcome
variables based on time enable studies with reasonable sample sizes. Sometimes it
is more difficult to obtain acceptance of randomisation in rehabilitation
patients than in acute patients. Some rehabilitation hospitals have only recently
begun to take an interest in controlled clinical trials, hence are not so
experienced. Nevertheless, controlled clinical trials delivering convincing
results are possible in rehabilitation medicine as well. But biometrical
consultation is necessary e.g. for study design, study conduction and evaluation.
Most important points are the methodology of the study design and its
practicability. Especially in these topics rehabilitation physicians and
biometrician have to cooperate.
PMID- 11008278
TI - [Patient expectations regarding methods and outcomes of their rehabilitation--a
controlled study of back pain- and cancer patients].
AB - Although patient expectations are important factors of the success of
rehabilitation, they have not yet received much attention in research. In the
present cross-sectional study, n = 248 rehabilitation patients, n = 160 suffering
from chronic back pain and n = 88 suffering from oncological diseases (breast
cancer, cervical cancer, ovarian cancer, colorectal cancer), were assessed at the
time of admission to a rehabilitation clinic, using a newly developed self-report
questionnaire to evaluate their expectations regarding the process and outcome of
their rehabilitation. Results show on an item level that non-specific process
expectations such as balneophysical treatments or features of the surroundings of
the clinic were most prevailing. Across both diagnostic groups, common goals of
rehabilitation such as reduction of complaints, physical fitness and recreation
scored highest. On the basis of factor analysis, 10 scales of process
expectations were constructed: medical attention, physical training, vocational
counselling, balneophysical treatment, health information, stress management
training, support groups, relief from the strains of everyday life, alternative
medicine, and pleasant surroundings. Nine dimensions of outcome expectations were
detected: ability for work, physical fitness, reduction of complaints, behaviour
change, reduction of body weight, positive body feeling, vitality, enjoyment of
life, and social contact. In the univariate analysis, orthopaedical patients
scored higher on balneophysical treatments and vocational counselling (process
expectations) as well as reduction of complaints and ability for work (outcome
expectations). However, there were effects of age, gender and working status,
too. Thus these differences between diagnostic groups turned out to be
nonsignificant after controlling for the effects of age, gender, and working
status. On the other hand, some effects of the medical condition had been hidden
in the univariate comparison and were only revealed when adjusting for the
moderator variables. Those differences show that oncological patients had higher
expectations than back pain patients. Patients' expectations were correlated with
functional status and, to a lesser degree, emotional distress and locus of
control. To conclude, our study demonstrated that medical condition,
sociodemographic factors, working status and functional capacity are important
determinants of patient expectations regarding the process and outcome of
rehabilitation.
PMID- 11008279
TI - [High-mountain climate therapy for skin diseases and allergies-- mode of action,
therapeutic results, and immunologic effects].
AB - Dermatological-allergologic climatotherapy is interpreted as a therapy within a
specific climate with proven therapeutic benefits, immediate and longterm.
Intensive classical dermatological in-patient therapy is combined with specific
climatic effects. Primarily, the climate of the high mountains (1560 m) and of
the North Sea islands is of proven efficacy for dermatoses and allergic diseases
such as atopic dermatitis (neurodermatitis), eczema, psoriasis, T-cell lymphoma,
bronchial asthma. Specialized therapeutic utilities exist. Directly influencing
climatic factors such as insolation, thermic-hygric and aerosol conditions
without or with diminished allergic potency and nonspecific stimulating climate
factors change immune functions and effect stabilization. The therapeutic
immediate and longterm efficacy of the high mountain climate is proven by
excellent follow-up results. Its superiority to the dermatological therapy
applied at home is evident. Measurement and analysis of climate efficacy has
however proven difficult because of its complexity. The findings of several
recent clinical and biochemical studies are presented.
PMID- 11008280
TI - [Causes and correction of abnormal gait patterns due to prosthesis in above-knee
amputees].
AB - Abnormal gait patterns cause an increase in the energy cost of walking in above
knee amputees. Disturbances of the walking pattern are often caused both by the
amputated patient himself and by incorrect prosthetic fitting. The early
detection and correction of causative factors is of great importance for
successful rehabilitation of these amputees. During the follow-up examinations
the prosthesis must be inspected for a correct fitting and individually
appropriate knee stabilizing components. Prior to any corrective measures it must
be excluded that the artificial limb has been put on incorrectly by the amputee
himself.
PMID- 11008281
TI - [Rehabilitation networking illustrated by case management after occupational
accidents].
AB - No net without a spider! After work accidents the victims can rely on the
infrastructure created by the German accident insurance scheme
(Berufsgenossenschaften). A surgeon, a so-called transit physician, is
responsible after acute treatments also for all phases of rehabilitation. A Case
Manager (Berufshelfer), an employee of the Berufsgenossenschaften, advises the
victim in all matters, including vocational rehabilitation and personal concerns.
Both factors combine to form a network that orientates on the social needs of the
injured worker, on the financial tasks of the insurance agency and on incentives
to the rehabilitation facilities. The goals comprise "rehabilitation before
compensation" and "job retention instead of job loss".
PMID- 11008282
TI - [Report on the symposium "Patient education--perspectives from patient-oriented
medicine" Bremen, Jan. 20-21, 2000].
PMID- 11008283
TI - [Workshop on "Work-related procedures within the framework of medical
rehabilitation" Wurzburg, Jan. 25-6, 2000].
PMID- 11008284
TI - [Cerebral seizures in neonatal period: semiology, evolution and factors of
influence].
AB - INTRODUCTION: In spite of their incidence being much greater than at any other
period during life, seizures occurring during the neonatal period are difficult
to identify, since their patterns are not well organized on account of
insufficient anatomical, physiological and/or biochemical development. OBJECTIVE:
To analyse the semiology of seizures during the neonatal period, their
classification and subsequent evolution. PATIENTS AND METHODS: We made a
retrospective study of 60 patients who had convulsions during the neonatal
period, selected from amongst the children admitted to the Neonatology Department
of the Hospital Infantil Universitario Virgen de Rocio in Sevilla, between 1990
and 1998. We investigated 22 medical variables related to the clinical history,
neurological examination, neuroimaging studies, EEG and drugs used. RESULTS:
Anomalies were found on the initial examination in 83.3% of the cases. The
hypoxic-ischemic syndrome was the commonest etiology, followed by hemorrhages,
metabolic disorders, cardiopathies, malformations and infectious diseases. From
the semiological angle, the seizures were seen as partial or generalised increase
in muscle tone, followed by clonias, hypotonias and subtle seizures. Cerebral
angiography was the most commonly used diagnostic imaging technique. There was a
statistically significant relationship between the appearance of sequelae and the
earliness of the occurrence of the seizures, but not with the duration, semiology
or frequency. CONCLUSIONS: Seizures in the newborn are habitually seen in the
hypoxic-ischemic syndrome, and usually present as alterations in muscle tone.
Phenobarbitone is still the drug of choice for the treatment of seizures in the
neonatal period.
PMID- 11008285
TI - [Type I neurofibromatosis presenting as a progressive cervical myelopathy. The
first case reported in Kaxinawa Indians].
AB - INTRODUCTION: Type I neurofibromatosis is an autosomal dominant disorder with an
estimated prevalence of 1/3,000. Half of the new cases are due to mutations;
their penetration is complete in adults and may affect any ethnic group. We
describe the first reported case of type I neurofibromatosis in a Kaxinawa Indian
from the state of Acre, Brazil, in whom the presenting symptoms were of
progressive tetraparesis due to multiple paraspinal neurofibromata. CLINICAL
CASE: A 16 year old indigenous Kaxinawa boy presented with progressive myelopathy
for the past six months. On neurological examination he had hyperreflexive
spastic tetraparesia, predominantly on the right side, with the sensory level at
C3/C4, multiple medullary automatisms and respiratory difficulty. He also had
diffuse cafe-au-lait stains, including one particularly prominent one measuring
15 cm on his right buttock. MR of the spine showed many hypo-intense lesions at
T1 and hyperintense lesions at T2, which took up contrast and were present at all
the conjugation foramens bilaterally. These lesions originated at the roots and
were suggestive of neurofibromata. On mediastinal tomography there were several
neurofibromata in the mediastinum. The patient had a surgical operation for
spinal decompression, with a laminectomy at C1/C2 and removal of the
neurofibromata on the spinal cord at C1 and C2. The patient has a sister with
multiple cafe-au-lait stains. CONCLUSIONS: Because of the traditional isolation
of the Kaxinawa Indians, with whom contact was made at the beginning of the
twentieth century, this first case reported of type I neurofibromatosis may be
due to a new mutation which presented as a florid form of the disease with
multiple spinal neurofibromata.
PMID- 11008286
TI - [Cerebral arteritis and psychic involution in children. A report of one case with
a good response to treatment].
AB - OBJECTIVE: To show the importance of the cerebral arteritis as etiology of the
language and the intellectual involution in children. CLINICAL CASE: A boy
started to show psychic and language involution since 18 months of life to arrive
to an autistic behavior. After showing normal results in all the studies
performed in order to investigate the possible etiologies, cerebral arteriography
was performed. Cerebral arteritis affecting especially the right opercular artery
was disclosed. Oral nicardipine administration was follow-up of a complete
recuperation. CONCLUSIONS: Cerebral arteritis is very seldom managed as the cause
of intellectual and/or language involution in children as it also occurs with the
syndrome of acquired aphasia. However, this pathology has a good response not
only to corticoids but also to calcium channel antagonists as it occurred in our
patient.
PMID- 11008287
TI - [Risk factors for ischemic stroke. I. Conventional risk factors].
AB - INTRODUCTION: Stroke, together with ischemic cardiopathy, may be considered to be
a vascular epidemic in the developed world, where it is a major social and health
problem. In Spain it is the commonest cause of death in women and the second
commonest in men. DEVELOPMENT AND CONCLUSIONS: In this article we review the risk
factors which cannot be modified (age, sex, inheritance, race, geography and
climate) and the well-established risk factors which can be modified (arterial
hypertension, cardiopathies with a high risk of embolization, markers for
atherosclerosis, diabetes mellitus and transient ischemic accidents). A wide
understanding of these risk factors permits the identification of persons with a
high risk of having an ischemic stroke. Therefore preventive and therapeutic
measures to reduce individual risk from strokes (and their recurrence) and hence
reduce morbimortality from this, can be designed.
PMID- 11008288
TI - [Diseases of mitochondrial DNA].
AB - INTRODUCTION: Human diseases caused by disorders of the mitochondrial metabolism
have been described more than 30 years ago. Some of these are associated to
defects in the oxidative phosphorylation system (OXPHOS system), the final
pathway of the mitochondrial energetic metabolism, that leads to the synthesis of
ATP. DEVELOPMENT: Part of the polypeptide subunits involved in the OXPHOS system
are codified by the mitochondrial DNA (mtDNA). In the last 12 years, mutations
(point mutations or deletions) in the mtDNA have been described and associated to
well defined clinical syndromes caused by defects in the OXPHOS system. The
clinical features of these diseases are very heterogeneous affecting in most
cases to a great variety of organs and tissues. CONCLUSIONS: The correct
diagnosis of these mitochondrial disorders require precise clinical,
morphological, biochemical, and genetic data. The rapid advances in genetic
analysis allow the rapid detection of mutations, even before the obtention of
other type of analysis.
PMID- 11008289
TI - [Cysteine proteinase and neurodegeneration].
AB - OBJECTIVE: This is a review of the part played by the cysteine proteases in
different physiological and pathological processes. DEVELOPMENT: Apoptotic
processes have a crucial function in control of the number of cells in
multicellular organisms, both during development and throughout life. Alterations
in these are closely related to different pathological processes, from cancer
(with fewer apoptotic processes) to the degenerative disorders in which apoptosis
is increased. Although the stimuli which may induce apoptosis are very varied,
the apoptotic phenotypes are similar. Different metabolic routes are involved in
apoptosis and in these changes, both in transcription and postranscription. The
latter form the basis of this paper. We review the role of the cysteine protease
family, in which the caspases and calpains are the best representatives, which
have been related to different degenerative models. In this review we describe
the stimuli and cascades of intracellular signalling which occur on activation.
CONCLUSION: These proteases are involved in many situations involving the
development and maintenance of the number of cells in the tissues, both
physiological and pathological. They may be considered to be possible therapeutic
targets in neurodegenerative diseases such as Alzheimer's disease, amyotrophic
lateral sclerosis, Parkinson's disease and Huntington's chorea.
PMID- 11008290
TI - [Practical considerations regarding the diagnosis and treatment of disorders of
movement in childhood].
AB - OBJECTIVE: Disorders of movement in children frequently cause difficulties with
both the semiology and the diagnostic approach. DEVELOPMENT: Based on our
experience, we analyze useful strategies to overcome these difficulties and
consider the clinical semiology, use of complementary tests and therapeutic
approach. CONCLUSION: Correct clinical identification is the essential basis for
differential diagnosis and therapeutic management of the disorders of movement.
PMID- 11008291
TI - [Gilles de la Tourette syndrome].
AB - OBJECTIVE: To make a specific review of the definition and symptomatology of
Gilles de la Tourette syndrome. DEVELOPMENT AND CONCLUSION: We made an basic
syndrome evaluation and at the same time established a relationship with/between
the most significant co-morbid features. We also refer briefly to current drug
treatment and dosage and mention some of the most relevant side-effects of these
drugs. The exact etiology of this disorder is still not fully understood but it
is thought to be due to autosomal dominant inheritance, with marked penetration
in males.
PMID- 11008292
TI - [Does the cerebellum play a part in cognitive processes?].
AB - OBJECTIVE AND DEVELOPMENT: We review the different cognitive and behaviour
disorders in whose genesis the cerebellum has been thought to play a part. These
disorders include infantile autism, Williams' syndrome, attention-deficit
hyperactivity disorder and congenital cerebellar hypoplasia. We also consider the
consequences of an acquired cerebellar lesion in the light of the following
neuropsychological sequelas. It would seem that the cerebellum is involved in the
functioning of the executive system due to its relationship with the prefrontal
operative system and in the function of the working memory, and may share some of
the characteristics of the acquired frontal syndrome.
PMID- 11008293
TI - [Right hemisphere syndrome in children: functional and maturity correlation of
non-verbal learning disabilities].
AB - INTRODUCTION: This review presents the maturational model of the right hemisphere
syndrome in children, its clinical manifestations and its relationship with non
verbal learning disabilities. DEVELOPMENT AND CONCLUSIONS: The white matter model
proposed by Rourke is presented and the clinical symptoms that are generally
associated with right hemisphere dysfunction, independent of which hemisphere is
affected, are highlighted. It has been proposed that the right hemisphere have
proportionally more white matter than the left hemisphere which implies different
adaptation processes for each one after brain lesions. There are different
factors that determine these results: brain plasticity acts in different ways in
each hemisphere; early brain injuries, affect specially right hemispheric
functioning in its abilities to be in charge of new material processing and
building new schemes that are also used by the left hemisphere. Some pathologies
that are related with the clinical manifestations of non-verbal learning
disabilities are presented. According with this model, they display basic
neuropsychological features, even though their clinical manifestations could
change between them. The Attention Deficit Hyperactivity disorder is specially
considered as the most recent evidence of right hemispheric dysfunction, although
results in this pathology are controversial, from the neuropsychological point of
view. In general, the right hemisphere lesion in children has different
implications when it is compared with adult's lesions. The white matter model
could explain different processes in the plasticity brain mechanism. Preservation
of basic language aspects is observed, but a deficit in non-verbal abilities that
interferes with normal functioning is a rule. A specific clinical profile of
assets and deficits is presented in most of the cases. These characteristics
should be considered in treatment implementations.
PMID- 11008294
TI - [Controversial or arguable therapies in neurodevelopmental disorders].
AB - OBJECTIVE: To analyze the therapies and methods not scientifically documented
that more frequently are offer and used for the treatment of neurodevelopmental
disorders. DEVELOPMENT: These therapies are divided into three main groups: a)
Therapies directed upon brain functioning; b) Therapies directed upon nutritional
needs, and c) Others. Parents and close relatives of children with developmental
disorders are vulnerable to any person, institution or method that offers a quick
and easy solution to their problem. It is a priority that all health
professionals are familiar with the unproven therapies, that are offered for the
therapy of developmental disorders, so that they can inform, educate and advise
correctly to parents and close relatives of their patients. To deal with unproven
treatments involves more than analyzing the available scientific data. It is
required a comprehension and understanding of the personal and family dynamics in
front of a threat of illness or disfunction. CONCLUSION: Responsible and well
informed parents in relation to an unproven therapy should be free and have the
right to decide whether or not to use a controversial procedure prior to a
scientific determination of its validity; they also must keep in mind that at
least some procedures, beside of not been useful, could be harmful for the
physical, emotional and economical well-being of the patient and/or his family.
PMID- 11008295
TI - [Risks and benefits of new antiepileptic agents in children].
AB - INTRODUCTION AND DEVELOPMENT: New antiepileptic drugs (AED) have generally a good
pharmacokinetic profile. Their mode of action remains imperfectly known.
Gabapentin (GBP), oxcarbazepine (OCBZ), topiramate (TPM), vigabatrin (VGB) and
tiagabine (TGB) are mostly effective for partial seizures; lamotrigine (LTG) is
efficacious for both partial and generalized seizures, it is also active in
treatment of Lennox-Gastaut syndrome for which felbamate (FBM) is also effective.
West syndrome often responds to VGB. The tolerance of the new AED is generally
satisfactory but some serious, late side-effects have become apparent. Because of
such possible toxicity, of the cost and of the remaining uncertainties about
indications, the new AED are used mostly as add-on therapy for epilepsies
resistant to conventional AED or as secondary monotherapy following withdrawal of
other drugs used as monotherapy. Some new AED (LTG, GBP, TPM, OCBZ) have proved
equal or sometimes superior to conventional agents. CONCLUSION: They may be
especially useful in the treatment of certain resistant epilepsy syndromes such
as Lennox-Gastaut and West syndromes for which conventional drugs often fail.
PMID- 11008296
TI - [Epilepsy and learning disorders].
AB - INTRODUCTION: Children with epilepsy have more behavioral and cognitive problem
than children with other chronic illness and children in the general population.
Risk factors are multiple probably involving a combination of seizure, family and
child variable, behavioral problems (depression, occur frequently but may be
unrecognized). Anxiety disorders and psychoses are less common. DEVELOPMENT: The
learning and behavioral found in epileptic children is multifactorial, first the
effects of the conditions causing the epilepsy, in addition the epilepsy itself
may cause, change in the nervous system through the metabolic and excitatory
effects of the seizure and the neurotransmitter elements involved at the membrane
level. The effects of the treatment modality, be it pharmacology or surgical may
also play havoc with cognition function. CONCLUSION: The neurobehavioral effects
of antiepileptic drug although probably less important with the newer agent than
in the past, must be considered especially in polypharmacy as recent report have
in dictated.
PMID- 11008297
TI - [Atypical evolutions of benign partial epilepsy of infancy with centro-temporal
spikes].
AB - OBJECTIVES: To stress that different atypical evolutions occur in the course of
disease in some patients with the so called benign partial epilepsies of
childhood (BPEC). To promote interest in finding clinical and/or
electroencephalographic clues to recognize which patients might be prone to
present these risks. METHODS: Follow up of 26 pediatric patients who started with
typical clinical and EEG features of benign childhood epilepsy with centro
temporal spikes (BCECTS) but presented reversible or persistent serious epileptic
events including status epilepticus and language, cognitive or behavioral
impairments. Repeated neurological examinations, EEG records and
neuropsychological evaluations were done in the course of up to 14 years. Brain
imaging studies (CAT and/or MRI) were obtained in all patients. RESULTS: Four
groups of patients were recognized: 11 children with atypical benign partial
epilepsy of childhood (ABPEC) followed during 4 to 13 years. All have finally
recovered and attend normal schools, although five have learning difficulties.
Three patients met diagnostic criteria for Landau-Kleffner syndrome (LKS). Two of
them recovered from aphasia and in one, some language difficulties persist. Seven
children showed status epilepticus of BCECTS but all of them are now normal after
3 to 14 years of follow-up. Five children showed mixed features of the three
groups mentioned above and three of them fulfilled the criteria for diagnosis of
the syndrome of continuous spike-wave during slow sleep (CSWS). CONCLUSIONS: A
small proportion of cases starting with BCECTS evolve into either ABPEC, LKS,
status of BCECTS or the syndrome of CSWS. Then, BCECTS is not always benign.
Clinical and EEG markers should be sought to predict these atypical evolutions.
PMID- 11008298
TI - [Staphylococcus aureus-related meningitis].
PMID- 11008299
TI - [Transient bilateral paralysis of abducens nerve in a newborn. A case report].
PMID- 11008300
TI - [Fukuyama type congenital muscular dystrophy (cerebro-muscular disease). A case
report].
PMID- 11008301
TI - [Purple glove syndrome].
PMID- 11008302
TI - [HIV superinfection: myth or reality?].
AB - Most viral infections result in lifelong immunity against the virus, which
prevents subsequent superinfection. In the light of recent findings on
recombination of different viral clades, infection with two different HIV strains
is unlikely to occur during primary infection. However, it is unclear whether
true superinfection occurs during chronic HIV infection. If it does occur,
superinfection could constitute a risk for HIV-concordant couples, since
transmission of drug-resistant or more virulent viruses may result in worsening
of the disease or treatment failure. We review the available data on
superinfection and conclude that HIV-discordant couples should be informed of the
theoretical risk of superinfection, especially where only one partner is
receiving effective antiretroviral treatment.
PMID- 11008303
TI - Intrathoracic tumours in von Recklinghausen's neurofibromatosis.
AB - We review our cases of a rare pathology, intrathoracic tumours in von
Recklinghausen's neurofibromatosis, involving 6 patients operated upon in our
Surgery Department for intrathoracic neurogenic tumors. All had had a positive
history of von Recklinghausen's neurofibromatosis prior to thoracic surgery. The
management of this rare condition is discussed. We describe the presentation of
the symptoms, the operative technique and the long-term outcome, when obtainable.
Our results are compared with those of other authors, and the management of these
cases is reconsidered. In conclusion, we recommend that thoracic surgery should
only be considered when the patient becomes symptomatic, since malignant changes
in the tumour are possible due to operative trauma.
PMID- 11008304
TI - [Frequency of HFE gene mutations and genotype-phenotype correlations in patients
with hereditary hemochromatosis in Switzerland].
AB - Hereditary haemochromatosis is one of the most common genetic disorders affecting
populations of European ancestry. Isolation of a strong candidate gene, the HFE
gene, allows genetic diagnosis in a large number of cases. However, different
mutation frequencies have been reported in hereditary haemochromatosis patient
populations from various geographic regions. Such data and phenotype-genotype
correlations from Swiss patients with hereditary haemochromatosis are lacking.
The objective of our study was to determine the frequency of HFE gene mutations
in Swiss patients with hereditary haemochromatosis and to describe the clinical
phenotype of patients with either a homozygous C282Y mutation or compound
heterozygotes. 71 patients with a clinical diagnosis of hereditary
haemochromatosis were identified through a questionnaire sent to physicians
caring for hereditary haemochromatosis patients. Pertinent clinical data, in
particular those reflecting iron body stores, were collected. Genotyping for the
C282Y and H63D mutation of the HFE gene was performed. In 90% of the cases a
mutation of the HFE gene was found. 86% of the patients were homozygous for the
C282Y mutation, 4% were compound heterozygotes for the C282Y and the H63D
mutation. Patients with the homozygous C282Y mutation showed a broad phenotypic
spectrum that could not be accounted for by age or sex differences only. Our
results demonstrate that within the Swiss population genetic testing can also
identify the vast majority of patients with hereditary haemochromatosis. However,
the diagnosis is not ruled out by a negative genetic test. Furthermore, a broad
phenotypic spectrum is associated with the homozygous C282Y mutation in Swiss
hereditary haemochromatosis patients. The implications of these findings for
planning of widespread genetic screening for hereditary haemochromatosis in the
general population are discussed.
PMID- 11008305
TI - [Primary bilateral adrenal lymphoma].
AB - When abdominal imaging reveals the existence of unsuspected adrenal masses, a
diagnostic strategy is necessary. We report the case of a woman presenting with
pulmonary embolism, in whom abdominal ultrasound revealed voluminous masses in
both adrenals without clinical or biological signs of hormone hypersecretion, but
with mild primary adrenal failure. From a CT scan-directed needle biopsy of the
right adrenal mass and subsequent staging we were able to diagnose a primary
bilateral adrenal lymphoma, diffuse large B-cell type (REAL/WHO). On CHOP
chemotherapy both adrenal masses decreased dramatically and the patient is in
remission 18 months later. Primary adrenal lymphoma is a rare condition, since 65
cases have been reported to date. Histological diagnosis is nevertheless
important, in view of the excellent response to specific therapy observed in some
cases.
PMID- 11008306
TI - [Unmasking an atrial flutter].
PMID- 11008307
TI - [Expert Health Promotion Panel of the Swiss Society of Prevention and Public
Health. Total health promotion policy].
PMID- 11008308
TI - [Health and human rights--development of a questionnaire for measuring perceived
human rights status].
AB - Health and human rights as interlinked concepts are a promising new avenue in
public health. The aim of this study was the development of a reliable and valid
instrument for the measurement of the human right status. The reliability and
validity of this new questionnaire for human rights (HRS = human right scale) was
measured within a group of Public Health students (n = 42) and the participants
of the KORA-fracture-study. Test-retest-reliability was 0.73 (ICC: 0.69) and
Cronbach's alpha was 0.66-0.79. The evaluation of the validity with the help of a
factor analysis and a reconstruction study pointed out, that the perceived human
rights status has to be treated as an interlinked and not divisible concept. Both
study groups showed deficits for items in the dimension justice and
participation.
PMID- 11008309
TI - [Prevalence of smoking habits of Upper Austria students of the 7th and 8th grade
and effect of smoking habits of family and peers].
AB - The aim of the study was to explore the prevalence of different smoking habits in
a population of Austrian pupils, 12 to 15 years old, and the relationship of
familial and peer group smoking customs with these habits. In 1997 a population
based survey (International Study of Asthma and Allergies in Childhood, ISAAC)
was conducted of all 7th and 8th grade school children of a district of Upper
Austria. Information on the smoking habits of the adolescents, the family
members, and of the peer as well as smoking habits of the teacher, gender, and
age of the children was collected. The overall-prevalence of having ever smoked
in this population is 57.8%. The percentage of eversmokers among the 12-year-olds
is 50%. This amount increases to 63.8% among the 14- to 15-year-olds. The odds
ratios for smoking daily is highest among those whose best friend smokes (OR:
70.63, CI: 9.19, 542.40). The risk of daily smoking increases also if the
siblings of the juvenile (OR: 4.71, CI: 1.15, 19.35) or the mother (OR: 4.95, CI:
1.67, 14.70) smoke. If the father smokes the risk to smoke monthly is increased
(OR: 2.09, CI: 1.28, 3.40). These results point to the fact that smoking
prevention programes should take into account the influence of peers and family
of the adolescents.
PMID- 11008310
TI - A survey of institutional influenza vaccination in Switzerland.
AB - In June 1998, a questionnaire was sent to evaluate the influenza vaccination
practices in Switzerland: 429 health care institutions were to assess the level
of influenza vaccination and the coverage of specific groups; each institution
was required to specify whether vaccination coverage was known precisely (based
on recorded data) or estimated. The response rate was 42.4%. Among institutions
which responded, the mean accurate vaccination coverage rate for all patients was
40% and the estimated rate was 29%; these rates were slightly higher for people
older than 65 years. For the entire staff, the accurate vaccination rate was 16%
(14% estimated) whilst for the medical staff, the mean coverage was higher at 30%
(measured) and 16% (estimated). The mean vaccination rate for patients and
residents was 59% in the French speaking region of Switzerland, 54% in the
Italian speaking canton, but only 37% in the German speaking region. The same
ranking was found for vaccination coverage of medical staff: 21% in the French
speaking region, 15% in the Italian speaking canton, and 13% in German speaking
areas. These results suggest that cultural differences could play an important
role in the attitudes and behaviour of the population regarding influenza
vaccination programmes among the linguistic regions in Switzerland.
PMID- 11008311
TI - [Congress report. 11. Clinical conference. Ultrasonography 2000-- trials,
advances and trends].
PMID- 11008312
TI - [Boredom and diagnostic dilemma of splenic ultrasonography].
PMID- 11008313
TI - [Frequency, pattern and differential diagnosis of echogenic splenic changes:
sonographic follow-up study].
AB - AIM: This study analyzes frequency, sonographic pattern and differential
diagnosis of echogenic splenic foci and the value of ultrasound follow-up
examinations. METHOD: Clinical data and ultrasound examinations of 137 patients
with echogenic splenic foci were evaluated. Patients with uncertain diagnosis
were identified and underwent a second examination (n = 31). RESULTS: Echogenic
splenic foci are extremely rare. We found 137 cases in 12 1/2 years (12.2 of
10,000 ultrasound examinations). 5 sonographic patterns with differing but
characteristic differential diagnosis were seen (round echogenic, round echogenic
with halo and/or central liquefaction, round predominantly echogenic with
hypoechoic parts, echogenic wedge-form, calcifications or gas). In patients with
underlying malignant disorders the splenic foci were benign in 26 cases (34.7%),
malignant in 36 cases (48.0%), and in 13 cases (17.3%) the diagnosis was
uncertain. In patients with benign disorders the foci themselves were benign in
59 cases (95%), and in 3 cases (5%) the diagnosis was uncertain. CONCLUSION:
Echogenic splenic foci are rare. Distinguishing between benign and malignant foci
based upon sonographic patterns alone is only possible in exceptional cases.
Short term follow-up ultrasound examinations taking into consideration the
patients' underlying disease lead to the correct diagnosis in most cases.
PMID- 11008314
TI - [Results of doppler sonography in normally functioning transjugular portosystemic
shunts].
AB - PURPOSE: The objective of this study was to evaluate blood flow changes inside
normally functioning transjugular intrahepatic portosystemic shunts (TIPS), using
Colour Doppler ultrasound (CDUS) and pulsed Doppler ultrasound (PDUS). MATERIAL
AND METHODS: In a prospective study 72 patients (mean age 54, range 36-78 years)
underwent TIPS placement, portal angiography, CDUS and PDUS examinations. Along
the TIPS Doppler measurements were taken at the portal in the central part and at
the venous end of the TIPS. RESULTS: In well functioning TIPS the mean peak
velocity (PV) on the portal side was 39 cm/s (range 22-72 cm/s), in the area of
the incoming right portal end, branch 62 cm/s (range 40-109 cm/s) and at the site
of the incoming hepatic vein 139 cm/s (range 88-220 cm/s). In the punctured
portal and hepatic vein the mean PV was 25 cm/s (range 15-30 cm/s) and 18 cm/s
(15-22 cm/s) respectively. CONCLUSION: A velocity gradient between the portal and
the venous side of the TIPS is a normal finding, caused by the branches of the
portal and hepatic vein, joining the TIPS from the side and is characteristic of
a normally functioning TIPS.
PMID- 11008315
TI - Comparison of portal venous flow in cirrhotic patients with and without
paraumbilical vein patency using duplex-sonography.
AB - AIM: In a prospective study we examined the effect of paraumbilical vein patency
on the portal venous blood flow in patients with liver cirrhosis by Duplex
sonography. In this context we investigated the influence of the aetiology and
the severity of cirrhosis on the development of venous paraumbilical shunts.
METHOD: In 70 patients (Child A: 16; Child B: 27; Child C: 27) with cirrhosis of
different aetiologies the portal venous flow velocity, the blood flow volume, and
the diameter of the portal vein were examined by Duplex sonography after an
overnight fast. RESULTS: 16 patients had a patent paraumbilical vein. The mean
portal venous flow velocity (19.2 +/- 7.8 cm/s) and the flow volume (1.29 +/-
0.50 l/min) were significantly higher in patients with paraumbilical vein patency
than in patients without paraumbilical shunts (14.4 +/- 4.6 cm/s; p = 0.029 and
0.88 +/- 0.34 l/min; p = 0.007 respectively). The prevalence of shunts of the
paraumbilical vein in cirrhotics was significantly lower in category Child A
(6.3%) than in Child B (25.9%; p = 0.011) and Child C (33.3%; p = 0.006).
CONCLUSION: The occurrence of relatively high portal blood flow velocities in
cirrhotics must remind the examiner of the potential existence of spontaneous
portosystemic shunts. Those shunts must be carefully looked for with colour
Doppler ultrasound. In order to assess the true parenchymal blood flow we suggest
to perform additional measurements of the right portal trunk and the left portal
vein distal to the shunt. With an increase in the severity of liver cirrhosis the
incidence of paraumbilical vein patency rises.
PMID- 11008316
TI - [Hypertrophic pyloric stenosis: sonographic monitoring of conservative therapy
with intravenous atropine sulfate].
AB - AIM: Ultrasound is the method of choice for the diagnosis of hypertrophic pyloric
stenosis (HPS). The purpose of this study was to evaluate the usefulness of
sonography in monitoring the efficacy of conservative therapy of HPS with
intravenous atropine sulfate. METHOD: 21 infants with HPS under i.v. treatment
with atropine sulfate were included. Pyloric sonomorphology, channel width and
passage of gastric contents through the pyloric channel were monitored daily. The
latter was examined with colour Doppler, too. If no clinical improvement was
observed after 6-8 days, sonography and colour Doppler sonography played a
crucial role in the decision whether to continue the conservative therapy or to
perform pyloromyotomy. RESULTS: Conservative treatment was effective in 13/21
infants. In 8 patients therapy was continued as sonography demonstrated the
passage of gastric contents despite lack of clinical improvement. In 4 patients,
due to the sonographic findings, impending surgery could be cancelled. Colour
Doppler sonography proved to be extremely useful in demonstrating passage of
liquid through the narrowed pyloric channel. No significant change in pyloric
morphology was seen. CONCLUSION: In HPS a conservative therapeutic approach with
atropine sulfate is justified considering a success rate of 62% (13/21). During
sonographic monitoring the detection of the passing of gastric content may be
crucial for continuation and success of conservative therapy. In those cases
colour Doppler sonography is a very useful method.
PMID- 11008317
TI - [Imaging of intra-arterial hepatic port catheter systems by power-doppler
sonography using contrast media--preliminary results].
AB - AIM: This study was designed to determine whether intra-arterial hepatic port
catheter systems can be adequately detected by contrast-enhanced power-Doppler
sonography. METHOD: 15 patients with a liver port system were investigated before
chemotherapy. Examinations were performed with short bolus injections of the
contrast medium Levovist in addition to angiographic imaging. RESULTS: Liver port
systems were easily detected by the contrast-enhanced power-Doppler method. In 11
out of 15 patients a correct flow of the contrast medium via the port system was
seen with both examination methods. One partially occluded hepatic artery was not
identified by power-Doppler despite correct flow of the contrast fluid. In one of
three patients showing an incorrect flow of the contrast medium the blood
circulated primarily through the splenic artery due to a dislocation of the
catheter tip. Circulation through both the hepatic and the splenic arteries was
shown in a second patient and an occluded right hepatic artery was demonstrated
in a third. All these findings were observed with both examination techniques.
CONCLUSION: Power-Doppler sonography provides a reliable image of the port
catheter system. This method can be used as a follow-up procedure to determine
the state of arterial hepatic circulation during chemotherapy.
PMID- 11008318
TI - [Three-dimensional ultrasound evaluation of the rotator cuff. Preliminary results
of clinical application].
AB - AIM: Accurate sonographic diagnosis of rotator cuff lesions mainly depends on
image quality and on the experience of the examiner. The present study was
performed to determine whether the use of three dimensional (3D) sonography
further increases the diagnostic yield of ultrasound examinations. METHOD: In a
prospective study 25 patients who later underwent shoulder surgery of the rotator
cuff were examined pre-operatively by ultrasound with two and three dimensional
ultrasound. RESULTS: With three dimensional ultrasound rotator cuff lesions were
more often correctly diagnosed (sensitivity of 100%) than with conventional 2D
sonography (sensitivity of 91.7%). Specificity with both methods was 84.6%
predictive value 92% and 88% respectively. In partial thickness tears, false
negative results were twice as common with 2D imaging. CONCLUSION: Although our
results are preliminary and have to be verified in a larger study, three
dimensional ultrasound appears to facilitate diagnosing of rotator cuff lesions
and partial thickness tears, in particular.
PMID- 11008319
TI - [Biliary-digestive fistula with gallstone ileus--a sonographic diagnosis].
AB - We demonstrate a patient with a fistula between the gallbladder and the small
intestine combined with a gallstone ileus of the small bowel, diagnosed by
ultrasound. Plain abdominal X-ray only revealed small bowel obstruction. All the
typical diagnostic criteria of a biliodigestive fistula could be detected by
ultrasound. The patient was operated and discharged a few days later. We
demonstrate that biliodigestive fistulas can be diagnosed by ultrasound.
PMID- 11008320
TI - [On the fate of lost gallstones].
AB - The spilling of stones during laparoscopic cholecystectomy occurs in 10% of the
operations. Late complications associated with this type of surgical procedure
are abscesses and fistulas in the abdominal cavity and abdominal wall. The time
elapsing between laparoscopy and clinical manifestation may be as long as 12
months. We present a case of a patient with localised abdominal pain in the upper
right abdomen two months after laparoscopic cholecystectomy. Sonography and CT
revealed a fat necrosis posterior of the rectus muscle. Examination of the
histological specimen confirmed a fat necrosis caused by two small pigmented
stones, spilled during laparoscopic cholecystectomy.
PMID- 11008321
TI - From food constituent to dietary supplement and drug. Is there a role for
antioxidants in treatment strategies?
PMID- 11008322
TI - Therapeutic potential of glutathione.
AB - Reactive oxygen species, formed in various biochemical reactions, are normally
scavenged by antioxidants. Glutathione in its reduced form (GSH) is the most
powerful intracellular antioxidant, and the ratio of reduced to oxidised
glutathione (GSH:GSSG) serves as a representative marker of the antioxidative
capacity of the cell. Several clinical conditions are associated with reduced GSH
levels which as a consequence can result in a lowered cellular redox potential.
GSH and the redox potential of the cell are components of the cell signaling
system influencing the translocation of the transcription factor NF kappa B which
regulates the synthesis of cytokines and adhesion molecules. Therefore, one
possibility to protect cells from damage caused by reactive oxygen species is to
restore the intracellular glutathione levels. Cellular GSH concentration can be
influenced by exogenous administration of GSH (as intravenous infusion or as
aerosol), of glutathione esters or of GSH precursors such as glutamine or
cysteine (in form of N-acetyl-L-cysteine, alpha-lipoic acid). The modulation of
GSH metabolism might present a useful adjuvant therapy in many pathologies such
as intoxication, diabetes, uremia, sepsis, inflammatory lung processes, coronary
disease, cancer and immunodeficiency states.
PMID- 11008323
TI - Glutathione in the prevention of cisplatin induced toxicities. A prospectively
randomized pilot trial in patients with head and neck cancer and non small cell
lung cancer.
AB - PURPOSE: Glutathione has been shown to be an effective chemoprotector against
cisplatin-induced side effects in patients with ovarian cancer. In view of this
fact, we performed a randomized clinical pilot-trial in the management of other
solid tumors in order to compare application of Glutathione to intensive
hydration in patients undergoing chemotherapy with a regimen including cisplatin.
PATIENTS AND METHODS: Twenty patients suffering from advanced non small cell lung
cancer (n = 6) or head- and neck cancer (n = 14) were enrolled in the study. All
patients received 80 mg/m2 cisplatin along with etoposide or 5-fluorouracil every
4 weeks. Patients randomized to application of Glutathione (n = 11) received 5 g
of Glutathione immediately before application of cisplatin followed by 2000 ml of
normal saline. Patients in the control group (n = 9) received 2000 ml electrolyte
infusion before and 2000 ml of normal saline with forced diuresis after
cisplatin. RESULTS: The intensity of hematologic toxicity was significantly less
pronounced in patients treated with Glutathione than in the control group
(hemoglobin: 10.7 vs 9.5 mg% respectively, p = 0.039; white blood cell count 3.3
vs 2.2 x 103/microliter respectively, p = 0.004; platelets 167 vs 95 x
103/microliter respectively, p = 0.02), whereas in terms of non-hematologic
toxicity no difference was observed. Objective remission occurred in 6 out of 11
evaluable patients from the group receiving Glutathione (55%; complete remission:
9%; partial remission: 46%), and in 4 out of 8 evaluable patients from the
control group (partial remission: 50%). However, there was no statistical
difference in terms of response and overall survival (13.5 months vs. 10.5
months) between the two groups. CONCLUSIONS: Application of Cisplatin and
Glutathione seems to be safe and feasible and the antitumoral efficacy of
cisplatin is apparently not impaired by the concomitant use of Glutathione in
patients with solid tumors.
PMID- 11008324
TI - Efficacy of standard treatment in patients with Hodgkin's disease--a single
center experience.
AB - Sixty-two consecutive patients with newly diagnosed Hodgkin's Disease (HD) were
treated at our institution between 1991 and 1998 in accordance with protocols
which we considered as optimal standard therapy. In patients with localised
disease, extended field irradiation alone was used initially but short duration
chemotherapy followed by involved field irradiation was given later. Initially,
MOPP/ABV chemotherapy was considered the standard treatment regimen for advanced
HD, subsequently it was replaced by ABVD treatment. At 5 years patients with
localised HD have a projected overall survival of 95% and a failure-free survival
of 72%. Relapses in patients treated with radiotherapy alone (6/16 cases) could
be successfully managed with chemotherapy in most cases (5/6). In advanced HD,
projected 5-year survival and failure-free survival are 100% and 80%,
respectively. No treatment-related deaths or secondary malignancies were
registered.
PMID- 11008325
TI - [Hormone replacement therapy with a transdermal estradiol gel and oral micronized
progesterone. Effect on menopausal symptoms and lipid metabolism].
AB - In a multicenter observational study, the efficacy and acceptance of two
different regimens of postmenopausal hormone replacement therapy in the form of a
combination of 17 beta-estradiol in percutaneous gel application and micronized
oral progesterone were evaluated. Forty-eight patients (aged 40-66 years)
received 2.5 g estradiol gel plus either continuously micronized progesterone 100
per day (group A) or, sequentially, 200 mg per day between day 16 and 25 of a
monthly cycle (group B) for two months. A significant reduction in typical
menopausal symptoms, especially vasomotor complaints like hot flushes or
sweating, was observed in both groups (score average at the beginning for hot
flushes: 2.0 in group A and 1.8 in group B; after two months of treatment, 0.7 in
group A and 0.4 in group B). Cholesterol levels were slightly reduced but
statistically significant (235.9 +/- 49.55 mg/dl vs. 226.3 +/- 52.24 mg/dl; p <
0.05) only in group A; a trend towards lower cholesterol was observed in group B
(236.5 +/- 47.82 mg/dl vs. 227.4 +/- 44.72 mg/dl). Lipoprotein (a) was also
significantly reduced in group A (32.57 +/- 36.52 mg/dl vs. 28.28 +/- 31.03 mg/dl
in group A; 31.7 +/- 28.42 mg/dl vs. 28.34 +/- 23.71 in group B; p < 0.05). The
overall acceptance of this therapy was excellent or good in 91.3% of group A and
92.8% of group B patients.
PMID- 11008326
TI - L-Tryptophan does not influence acute ventilatory response at moderate altitude.
AB - Altitude induced insomnia is a very common symptom in mountaineering.
Conventional hypnotics such as benzodiazepines potentially can be associated with
untoward side effects because they can impair ventilatory adaptation to hypoxia
at altitude. The objective of our study was to evaluate the effect of a
alternative potentially sedative drug, L-tryptophan on ventilation at moderate
altitude. STUDY DESIGN, METHODS AND RELEVANT RESULTS: Randomised, double blind,
placebo controlled crossover trial. Blood gas analysis of 8 healthy subjects was
performed before and one hour after oral administration of 500 mg L-tryptophan or
placebo at altitudes of 171 m and at 3,000 m. PaO2 and PaCO2 before and after L
Tryptophan or placebo medication did not change significantly at neither level of
altitude investigated. CONCLUSION: L-tryptophan does not impair ventilatory
adaptation to mild hypoxia at moderate altitude.
PMID- 11008327
TI - Successful use of continuous intravenous prostacyclin in a patient with severe
portopulmonary hypertension.
AB - INTRODUCTION: Portopulmonary hypertension, defined by a mean pulmonary artery
pressure > 25 mm Hg in the presence of normal pulmonary capillary wedge pressure
and portal hypertension, is a known complication of end-stage liver disease that
has been associated with high morbidity and mortality at the time of liver
transplantation. DESIGN: Descriptive case report. PATIENT: A 32 year old male
patient suffering from end-stage hepatitis C liver cirrhosis presented with
severe portopulmonary hypertension. At presentation the following pulmonary
hemodynamics were measured: systolic pulmonary artery pressure (PAP) 76 mm Hg,
mean PAP 42 mm Hg, pulmonary vascular resistance index (PVRI) 931, pulmonary
capillary wedge pressure (PCWP) 9 mm Hg, and cardiac output (CO) 4.03 l/min.
INTERVENTION: After acute hemodynamic testing the patient received 8 ng/kg/min
epoprostenol (prostacyclin) by continuous intravenous infusion with an infusion
pump. Hemodynamic evaluation was performed monthly by transthoracic
echocardiography and right heart catheterisation after 5 months. RESULTS: After 5
months of continuous therapy right heart catheterisation revealed the following
hemodynamics: systolic pulmonary artery pressure (PAP) 59 mm Hg, mean PAP 32 mm
Hg, pulmonary vascular resistance index (PVRI) 561, pulmonary capillary wedge
pressure (PCWP) 7 mm Hg, and cardiac output (CO) 6.95 l/min. This presents a
decrease in systolic pulmonary artery pressure of approximately 22%, a decrease
in mean pulmonary artery pressure of approximately 30%, a decrease in pulmonary
vascular resistance of approximately 40% and an increase in cardiac output of
approximately 73%. Echocardiography demonstrated a decrease in estimated systolic
pulmonary artery pressure of about 37% after 8 months of therapy. No
complications were observed during epoprostenol therapy. CONCLUSION: In this
adult patient suffering from end-stage liver disease and portopulmonary
hypertension, administration of continuous intravenous epoprostenol resulted in
significant reduction of pulmonary hypertension and therefore in acceptance for
orthotopic liver transplantation. Utilisation of this new therapeutic strategy
might be a helpful pharmacological tool for patients with portopulmonary
hypertension to make them acceptable for orthotopic liver transplantation.
PMID- 11008328
TI - [Hitler and the anti-smoking movement in the time of national socialism].
PMID- 11008329
TI - [Effect of ACE-inhibitors on left ventricular remodeling after acute anterior or
posterior myocardial infarct. Cine- magnetic resonance tomography study].
AB - The question whether patients with posterior infarctions (PMI) have a comparable
benefit of an ACE-inhibitor therapy to those with anterior infarction (AMI) is
still open. The study was undertaken to investigate the different influence of
ACE inhibitors on the remodeling of the left ventricle after AMI or PMI. 52
patients (Pt.) (17 female, 38-73 years) were randomized to receive either 25-75
mg/day captopril (C) or 5-20 mg/day fosinopril (F) beginning on day 7 after acute
myocardial infarction. 28 Pt. had AMI, 24 Pt. PMI. Infarct size was determined by
the creatine kinase integral method. 50 Pt. were examined by cine magnetic
resonance imaging 1 and 26 weeks after infarction. We determined: left
ventricular end-diastolic (LVEDVI) and end-systolic (LVESVI) volume index,
ejection fraction (EF), infarction weight (IW), left ventricular muscle mass
(MM), systolic wall thickening (SWT) and motility (MOT) of the vital myocardium,
and clinical behavior according to the guidelines of the New York Heart
Association (NYHA). The results were compared with those of a sample (V) without
ACE inhibitor therapy (10 females, 21 males, 36-75 years, 19 AMI, 12 PMI). There
were no significant differences between C and F. Without ACE-inhibition therapy
LVEDVI increased by 28.2% in AMI, by 18.4% in PMI (p < 0.001), with ACE
inhibition by 13.7% in AMI and by 9.9% in PMI (p < 0.001). LVESVI increased in V
by 40.1% in AMI, by 28.5% in PMI (p < 0.001). With ACE-inhibitor we found an
increase of 11.2% in AMI and 5.3% in PMI (p < 0.001). EF decreased without ACE
inhibitor by 18.7% in AMI and by 10.2% in PMI (p < 0.001), with ACE-inhibition
increased by 4.3% in AMI and PMI, respectively (n. s.). NYHA got better in all
groups, by 17.4% in AMI and 20.8% in PMI without ACE-inhibitor (n.s.), by 45.5%
in AMI and 31.6% in PMI with ACE-inhibitor (p < 0.001). IG increased by 15.5% in
AMI and 8.8% in PMI in V (p < 0.001), by 11.2% in AMI and 5.3% in PMI with C or F
(p < 0.001). MM got bigger in V by 16.6% in AMI and 12.7% in PMI (p < 0.05), with
ACE-inhibitor by 11.7% in AMI and 8.0% in PMI (p < 0.05). sWD increased by 12.9%
in AMI and by 6.7% in PMI in V (p < 0.01), by 37.1% in AMI and 88.0% in PMI with
C or F (p < 0.001). MOT decreased by 39.6% in AMI and 14.9% in PMI without ACE
inhibition (p < 0.001) and increased by 4.3% in AMI and by 5.0% in PMI with ACE
inhibitor (n. s.). All differences between V and the ACE-inhibitor groups were
significant. Even patients with PMI clearly benefit from ACE-inhibitor therapy,
but less than those with AMI. Captopril and fosinopril show no different effects
after myocardial infarction.
PMID- 11008330
TI - [Certain aspects of plastic surgery in the head and neck area].
AB - The spectrum of plastic surgery in the head and neck area is wide. The
indications for as well as potentials and limits too, aesthetic surgery cannot be
pressed into a rigid framework. The operative strategy will substantively depend
on several factors, including objectivated local findings from, as well as
general situation and motivation, of the patient. In plastic surgery the
psychological situation of the patient is very often paramount, especially as
regards cosmetic aspects. Sometimes the declared motives of the patient hide
emotional disorders. Several examples show the practicability and limits. The
possibilities of corrective action depend not only on the local findings but also
on the surgeon's experience and skill.
PMID- 11008331
TI - [Osteoporosis in Turner syndrome with chromosomal mosaicism (45,XO/46,XY). A case
report].
AB - We report a rare case of Turner's syndrome (UTS) due to a gonosomal mosaic
45,X0/46,XY with the main clinical feature of several fractures in the course of
osteoporosis. The bone mineral density (BMD) of the lumbar spine and the hip
measured by DXA showed osteoporosis. The other clinical investigations including
laboratory parameters presented beside an estrogen deficiency due to primary
amenorrhea, a small thyroid with hypothyroidism, increased renal calciuria and
increased markers of bone metabolism. Beside the supplementation of estrogen and
thyroid hormone deficits, only a combination of different bone-associated drugs
could normalize the bone mineral density and the bone turnover. During a two
years' follow-up period no further fractures occurred. Furthermore, theories
regarding the occurrence of osteoporosis and other complex pathologies in UTS are
discussed with the conclusion that osteopenia in UTS is probably based on a
multifactorial genesis. Due to these complex pathologies during adulthood,
patients with UTS should get multidisciplinary care in order to reduce morbidity
and preserve quality of life.
PMID- 11008332
TI - [History of neurosurgical treatment of gunshot wounds].
AB - The provision of neurosurgical managing care in the German field hospital during
the IFOR- and SFOR-mission in the former Yugoslavia is a novum within the NATO.
Penetrating head trauma is by far the most common type of central nervous system
trauma observed in a military combat setting. There is a distinct advantage
realized by early intervention following penetrating head trauma with increased
intracranial pressure. As well as the experience of Ernst von Bergmann a hundred
years ago during the Prussian-Austrian-War as the reports of the operation Desert
Storm confirm the advantage of an early neurosurgical intervention of gunshot
wounds of the head. The decision of the German Armed Forces to provide forward
located neurosurgical maintenance is justified and will lead to major reduction
of time between injury and surgery. In the future neurosurgical managing care in
combat settings will be supplemented and improved by peer-to-peer networks
through the World Wide Web.
PMID- 11008333
TI - [Cesarean section by patient request--permissive obstetrics or acceptable as self
determined delivery?].
PMID- 11008334
TI - [Nausea and vomiting in early pregnancy/hyperemesis gravidarum. Current status of
psychosomatic factors].
AB - BACKGROUND: Although Hyperemesis gravidarum (HG) is still a disease of unknown
aetiology psychosocial aspects are involved in the genesis of this disease.
MATERIALS AND METHODS: Based on experiences in our department and on actual
literature psychosocial aspects and therapeutic approaches of HG are presented.
RESULTS: Predisposing factors of HG are stress, inadequate information about
pregnancy or delivery and problems in the marital relationship. Feelings of
ambivalence towards pregnancy, a distorted perception of reality, the unconscious
refusing of a wanted child and the worry about a relation between nutrition of
the foetus and the HG have influence on the development of the HG. The role of
the social context, especially the mother, of expectations towards vomiting and
of secondary gain in the genesis and the evaluation of HG is explained.
Therapeutical approaches beside the known somatic therapies are acupuncture, the
electric stimulation of the N. vestibularis and different methods of
psychotherapy, which can include the partner or other persons from the social
context. In some cases an intensified therapy under in-patient conditions can
improve therapeutic results. DISCUSSION: Psychosocial factors are involved not
only in the genesis of HG, but also in the duration and intensity of symptoms as
well as in the resistance especially, towards isolated somatic therapeutical
approaches. CONCLUSIONS: When psychosocial factors are taken into account in the
search for a cause and the treatment of HG results of treatment are more
successful and persist over a longer time.
PMID- 11008335
TI - [Doppler ultrasound examination of fetal umbilical arteries of the intra
abdominal segment in normal singleton pregnancies].
AB - BACKGROUND: In the management of high risk pregnancies, blood flow measurements
in the umbilical arteries (Aa. umb) have reduced perinatal morbidity and
mortality. No consensus has been reached about the optimal location of
measurements along the umbilical cord. The present study analyses the blood flow
in both umbilical arteries where they pass by the fetal bladder. PATIENTS AND
METHODS: In 48 normal pregnancies, Doppler examinations were used to measure the
pulsatility indices (PI). From the 20th week of pregnancy onward, the PI were
measured once every four weeks in the intraabdominal segments of the right and
the left Aa. umb. lateral to the fetal bladder. Measurements were also done in a
free loop and at the placental insertion. RESULTS: For all locations, normal
ranges were calculated. The PI at all four sites decreased as the pregnancies
were approaching term. In the III. trimester, the standard deviations of PI were
smaller than in the II. trimester. The PI at the intraabdominal segment of the
right and the left umbilical arteries turned out to be similar to each other and
exceeded the values measured at the free loop and at the placental insertion
respectively. CONCLUSION: The intraabdominal segments of the umbilical arteries
were defined as a new location for PI measurements. When adopting a fixed place
of measurement, it is likely that the reproducibility of PI measurements will be
increased. DISCUSSION: The higher PI at the intraabdominal segment of the
umbilical arteries are caused by the more central location compared to the
placental insertion.
PMID- 11008336
TI - [Intercellular adhesion molecular 1, a diagnostic serum marker in
chorioamnionitis, pre-eclampsia and HELLP syndrome].
AB - INTRODUCTION: Chorioamnionitis and pregnancy-induced hypertension both are
extremely feared complications of human pregnancy. Activation or disturbance of
normal endothelial cell function may be involved in the pathogenesis of both
kinds of disease. The aim of our study was to compare the diagnostic value of
soluble intercellular-adhesion-molecule-1 (ICAM-1) with that of C-reactive
protein (CRP) and white blood cell count for the detection of chorioamnionitis in
patients with preterm labor. In addition, we examined if concentrations of ICAM-1
were also increased in case of preeclampsia or HELLP-syndrome. MATERIALS AND
METHODS: ICAM-1, CRP and leucocyte count were estimated in 50 cases of normal
term delivery, 97 cases of uncontrollable preterm labor, 16 cases of preeclampsia
and 9 cases of HELLP-syndrome before delivery. RESULTS: From 97 women delivering
preterm, chorioamnionitis was histologically confirmed for 48 women. Maternal
serum levels of ICAM-1 (p < 0.001), CRP (p < 0.001) and leucocyte count (p <
0.02) were significantly higher in the group of preterm delivering patients (< 37
weeks gestation) with histologically confirmed chorioamnionitis in comparison to
preterm delivering patients in the absence of chorioamnionitis. In the group of
patients delivering preterm (< 37 weeks gestation) because of preeclampsia or
HELLP-syndrome, ICAM-1 (p < 0.001), as well as CRP (p < 0.006) concentrations
were also significantly increased in comparison to patients delivering preterm in
the absence of chorioamnionitis. CONCLUSIONS: Elevated levels of ICAM-1 in the
serum of pregnant women may be considered as an important risk factor for the
development of complications in pregnancy associated with inflammatory induced
changes of maternal endothelial cell functions.
PMID- 11008337
TI - [Significance of uterine contractions for adaptation of the newborn infant before
cesarean section].
AB - There are quite a few publications on the influence of labour on the adaptation
of neonates after elective cesarean sections. Many authors recommend the
induction of labor prior to the cesarean section. They found that this improves
the adaptation of the infants. MATERIAL AND METHOD: All cesarean sections between
1991 and 1996 are recorded. Mature neonates (> 36 weeks of pregnancy) were
evaluated separately from premature infants (< 36 weeks of pregnancy). As target
parameters we chose 1. the condition of the neonates (characterized by the Apgar
Score, the pH of the umbilical cord artery, and the requirement of artificial
respiration). 2. the necessity of transfer to the neonatologic intensive care
unit. Concerning these parameters, the immature neonates (> 36 weeks of
pregnancy) were evaluated separately from the mature infants (< 36 weeks of
pregnancy). In the latter group we finally evaluated the data of those who were
not delivered by a cesarean section because of intrauterine fetal distress.
RESULTS: The adaptation of the premature neonates was so closely related to the
gestational age that all the other variables were of no statistically significant
influence. Thus also the factor "labour" was of no influence. The results in the
group of the mature infants were completely different. Between week 36 und 42 of
pregnancy the gestational age was of no influence on the adaptation of the
neonates. Statistically noticeable however was the influence of preoperative
labour: The adaptation of infants delivered by cesarean-section after labour was
remarkably worse than the adaptation of those who were delivered without labour
prior to the operation. This statement is also correct when one rules out those
infants who were delivered by a so called emergency cesarean section. When
evaluating the group of neonates in which the cesarean section was not performed
because of intrauterine fetal distress we could find no influence of preoperative
labour on the adaptation of the infants. All other variables examined (e.g.
maternal age, parity, duration of labour, method of anaesthesia, twin-pregnancy)
were no factors of influence on the adaptation of the babies. CONCLUSION: From
our results we cannot support the recommendation to induce labour prior to any
elective cesarean section by infusion of oxytocin or to wait for the spontaneous
onset of labour. There ist no reason to change our policy to perform an elective
cesarean section as near as possible to term before the onset of labour.
PMID- 11008338
TI - [Fetal complications after failed pregnancy termination in the first trimester].
AB - BACKGROUND: Two different methods are in use for induction of abortion: either
dilation and curettage (D & C) or medical termination with antigestagens and/or
prostaglandins. The risk of continuing pregnancy after D & C ranges from 0.023 to
1% and is inversely correlated with gestational age. METHODS AND RESULTS: Several
authors reported fetal anomalies (limb and oro-facial defects) in such cases. For
the medical induction of abortion a combination of Mifepristone and Misoprostole
is the treatment of choice in order to reduce the risk of ongoing pregnancy.
Using single drug therapy carries an increased risk of failure and of subsequent
fetal anomaly. There seems to be an increased incidence of limb defects and
Mobius' syndrome in fetuses born after failed termination of pregnancy, but
normal fetal development is entirely possible. CONCLUSION/DISCUSSION: The
patients concerned must be informed in detail of the risks and probable
consequences which must be included in the counselling concept of the treating
gynaecologist.
PMID- 11008339
TI - [Malignant melanoma and pregnancy].
AB - BACKGROUND: Incidence of malignant melanoma has more than doubled in the past 10
years. Two thirds of malignant melanoma arise from melanocytes, the pigmented
cells of epidermis and dermis, in one third of the cases from preexisting nevi.
CASE REPORT: We report on a 39 year-old pregnant woman with liver metastases
after surgical removal of a malignant melanoma two years before. The mother died
in the course of progredient liver insufficiency, a male baby had been delivered
with a gestational age of 26 weeks + 4 days via cesarean section 11 days before
and developed normally. RESULTS: Early diagnosis and operative excision are
decisive for survival, in advanced stages chemotherapy does not prolong survival.
CONCLUSIONS: Interdisciplinary co-operation of the pediatrician, obstetrician,
and oncologist is of utmost importance. DISCUSSION: Melanoma and pregnancy
represent a difficult situation for the patient, her partner and the treating
physicians. Here the wish to have a child meets the potentially deadly cancer
disease.
PMID- 11008340
TI - [Are guidelines needed for diagnostic psychological testing in child- and
adolescent psychiatry?].
PMID- 11008341
TI - [Utilization of psychological tests for diagnosis in German child and adolescent
psychiatry: results of a survey].
AB - 92 inpatient and outpatient child and adolescent psychiatric institutions all
over Germany were surveyed on practice and attitude towards psychological tests.
Leading psychologists were contacted by mail and given a 15 item questionnaire.
All institutions reported keeping at least a small test-inventory and using
psychological tests in diagnostics. Half of the clinics carried out individual
tests obligatory in the routine. Additionally, one third applied self-constructed
instruments, which in the minority of cases had been psychometrically
investigated or published. Computer-aided testing was established in one third of
the institutions. Colleagues, test-compendia, scientific journals and the
internet are quite often consulted for test-information. Intelligence measures
are the most frequently administered test in child and adolescent psychiatry,
while structured interviews are applied rarely. Among the highly frequent used
individual tests were the Wechsler-Intelligence-Scales for children and adults,
the CFT-scales, the projective Sceno-test and the d2-attention endurance test.
One forth of the surveyed clinics reported refusal of individual or groups of
tests, including projective and cognitive assessments. Thereby, ethic aspects
were never mentioned as a reason for rejection. A range of diagnosticians
reported to miss adequate measures for diverse constructs, e.g. learning
disabilities. Furthermore, new norms and up-dates for regularly used instruments
were often demanded. Some single survey-results also give reason for critically
reviewing aspects of test-usage in German child and adolescent psychiatry.
PMID- 11008342
TI - [Psychological testing in theory and practice exemplified by intelligence
testing].
AB - OBJECTIVES: The U.S.-American standards of quality for psychological diagnostics
tests were published in 1998 in German translation under the title "Standards fur
padagogisches und psychologisches Testen". The relevance of these Standards for
studies of psychological testing in child and adolescent psychiatry is discussed.
Important intelligence tests will be assessed on the basis of these standards for
studies of psychological testing in children and adolescents. METHODS: Relevant
standards were presented and discussed. The intelligence tests HAWIK-R, HAWIK
III, K-ABC, AID, PSB, I-S-T 70, SPM, CFT 20, CMM-LB, SON-R 2 1/2-7, SON-R 5 1/2
17 were analyzed with regard to whether or not they fulfilled the Standards under
inclusion of the test manuals, test reviews, and empirical studies from the
literature. RESULTS: The intelligence tests listed differ widely in the extent to
which they meet the Standards. CONCLUSIONS: The Standards appear, at least in
part, to be relevant to studies of psychological testing in child and adolescent
psychiatry. The intelligence tests used in such studies should be critically
examined with regard to their quality and whether or not they are suitable for
the issues to be resolved. Given their completely outdated standard, it is
recommended to refrain from further use of PBS and I-S-T 70.
PMID- 11008343
TI - [Neuropsychological testing in childhood and adolescence].
AB - Among a number of issues and disorder pictures neuropsychological diagnostics
should occupy a solid position, both in the initial assessment, as well as in
that of the course. With an eye towards its use in child and adolescent
psychiatry, a descriptive definition of this area of psychological diagnostics
must be provided. In so doing, several essentially different approaches arise,
whose effects on psychometrics and interpretation must be examined. Regardless of
the fact that the current availability of standardized neuropsychological
diagnostics is satisfactory only in certain areas, the methods used in clinical
practice and/or research are presented. In addition to the individual test
batteries, individual test methods for the areas of visual and auditory memory
functions, attention functions, functions associated with speech, and executive
functions are discussed. The current status of neuropsychological diagnostics
generates essential tasks towards its further development. This is true with
regard to goals attainable in the short term, such as adaptation or
standardization of available instruments, as well as for long-term research
tasks.
PMID- 11008344
TI - [Diagnostic testing methods for skill assessment in reading, writing, and
arithmetic. A critical review].
AB - OBJECTIVES: The diagnosis of a specific developmental disorder of reading,
writing and arithmetic can be made based upon individually applied standardized
methods for testing scholastic achievement and IQ. To make the choice of suitable
methods easier for the administrator of the test, a critical survey of German
language methods for assessing skills in reading, writing and arithmetic is
presented. METHODS: Test intention and psychometric properties for scholastic
achievement are summarized. The methods are assessed with regard to their utility
in the diagnosis of congenital alexia and dyscalculia. Supplementary suggestions
for clinical assessment are given. RESULTS: In summary, beyond the primary school
area there is a lack of current standardized methods that meet the current
standards of quality. Particularly the assessment of arithmetic skills above
those of the 4th grade level require resorting to methods of dubious curricular
validity. Coverage is once again better for the upper elementary and middle
school levels. CONCLUSIONS: There is a need for new constructions, respectively a
need to update published scholastic achievement tests.
PMID- 11008345
TI - [Gottinger Form Reproduction Test (GFT)--results from an unselected sample].
AB - The Gottingen Form Reproduction Test (GFT) is a relatively old method of
assessing visuo-motor coordination that is still often performed in clinical
practice. Based on a sample of 72 unselected second-graders, it was shown that
the mean percent ranks are too high. GFT percent ranks then should be interpreted
with extreme caution in the course of clinical diagnosis.
PMID- 11008346
TI - [Are eight-year olds already suffering from panic disorder? Investigation of
prevalence with focus on panic disorder and agoraphobia].
AB - A representative sample of 826 eight-year-old second-graders in Dresden was
examined in a two-stage procedure to ascertain the 6-month prevalence of DSM-IV
anxiety disorders. Particular care was taken to assess panic disorder. The eight
year-olds had already been interviewed personally in a screening session and in
230 children an individual diagnostic examination with a structured diagnostic
interview was carried out. The total prevalence of anxiety disorder was 9.5%. No
case of either panic disorder or agoraphobia was found. For the diagnosis of
agoraphobia the DSM-IV diagnostic criterion was lacking in which situations
typical to agoraphobia are feared or avoided because escape would be difficult or
it would be difficult to reach help. Eight-year-olds do not forge this cognitive
link. In agoraphobic situations 2.5% of the children (almost exclusively, girls)
suffer from a specific phobia. The prevalence of anxiety disorders is markedly
higher among girls than in boys.
PMID- 11008347
TI - [The autopsy in crisis].
AB - In the Western world the autopsy rate is declining at an alarming rate. In the
United States of America the rate in some academic hospitals is less than 7% of
all hospital deaths. This decline has been documented and deplored in many
countries, articles and books. Suggestions on how to resuscitate the autopsy
range from mandatory in all hospital deaths to economic bonuses to the doctors
obtaining the highest autopsy rate. All in vain, the autopsy decline continues.
Pathologists deploring this decline blamed clinical colleagues, new social
attitudes, the litigious nature of modern society, but few have questioned a
procedure little changed in more than a century. Perhaps the time has come to
abandon the "classic" autopsy and rethink the procedure so as to make it useful,
alluring and indispensable for the contemporary, concerned clinician.
PMID- 11008348
TI - [Evaluation of acute effect of GnRH administration on leptin secretion in normal
and hyperandrogenic women].
AB - BACKGROUND: Several studies suggest that leptin modulates the reproductive axis
function. Leptin may stimulate release of GnRH from hypothalamus and of
gonadotrophins from the pituitary. A synchronicity of LH and leptin pulses has
been described in healthy women and in patients with polycystic ovarian syndrome
(PCOS), suggesting a relationship between the episodic secretion of LH and
leptin. In vitro experimental studies have demonstrated that leptin
administration promotes GnRH-LH release. However it is not established whether
GnRH promotes the episodic secretion of leptin. AIM: To assess the response of LH
and leptin to the administration of a GnRH bolus in hyperandrogenic and healthy
women. PATIENTS AND METHODS: Eleven hyperandrogenic and eleven healthy women of
similar age and body mass index (BMI) were studied. Under basal conditions three
blood samples were collected every 30 min before and after the administration of
a GnRH bolus (100 micrograms). LH and leptin concentrations were measured in all
samples. Testosterone, SHBG and estradiol were determined in the first sample.
For data analysis, the increment of LH and leptin between 0-30 and 0-60 min was
calculated. The LH and leptin areas under the curve (AUC) before and after GnRH
administration were also calculated in both groups. RESULTS: After GnRH
administration an increment in LH concentrations was observed in both groups;
however, leptin concentrations were not modified. In both groups LH area under
the curve increased after GnRH administration; however, the leptin area was not
modified. CONCLUSIONS: These results suggest that circulating leptin
concentration is not modulated by GnRH-LH.
PMID- 11008349
TI - [Improvement in inspiratory muscle function in patients with mitral stenosis
after percutaneous mitral valvuloplasty. Preliminary communication].
AB - BACKGROUND: It has been proved that there is an inspiratory muscle dysfunction in
mitral stenosis; Although its causes still remain unknown. AIM: To evaluate the
effect of percutaneous balloon mitral valvuloplasty (PMV) on inspiratory muscle
performance (IMP) in patients with mitral stenosis (mitral area < 1.5 cm2).
PATIENTS AND METHODS: We studied IMP in 8 patients (35 +/- 10 years) before and 3
months after successful PMV. Inspiratory muscle strength was studied by measuring
maximal statistical inspiratory mouth pressure (MIP). Endurance was evaluated
using a two minute incremental threshold loading test in order to obtain the
maximal sustainable inspiratory pressure (SIP), with the maximal sustainable load
(MSL) the patients could sustain for 2 minutes. RESULTS: Mitral valvuloplasty
increased mean cardiac index from 3.1 +/- 0.3 to 4.15 +/- 0.3 l/min/m2 (p <
0.01), and significantly decreased mean pulmonary and capillary pressures. The
MIP value(118 +/- 6 cmH2O), similar to that of normal group, increased to 137 +/-
7 cmH2O (p < 0.01). SIP and maximal sustainable load were 52 +/- 3 cmH2O and 294
+/- 29 g respectively, lower than normal subjects (p < 0.05). They increased
after PMV to 80 +/- 3 cmH2O and 463 +/- 26 g respectively (p < 0.001).
CONCLUSIONS: PMV improved inspiratory muscle function in patients with severe
mitral stenosis, probably secondary to a decrease work of breath and improvement
of ventricular function.
PMID- 11008350
TI - [Antihypertensive effects of valsartan. National multicentric study].
AB - BACKGROUND: Valsartan is an angiotensin AT1 receptor antagonist. Clinical studies
have shown that this is an effective and well tolerated drug. AIM: To compare
valsartan with other commonly used antihypertensives in a National multicentric
study. MATERIAL AND METHODS: Between 1997 and 1998, a pharmacological
surveillance of patients with mild or moderate hypertension, coming from
different regions of the country, was carried out. Patients were followed during
8 weeks. In the group treated with valsartan, the initial dose was 80 mg/day.
After four weeks of therapy, and according to patient's response the dose of
valsartan or of the other antihypertensives was modified. RESULTS: Five hundred
ninety three patients, aged 59 years old as a mean, were included in the study.
Of these 434 (265 female) received valsartan and 159 (101 female) other
antihypertensive drugs. Fifteen percent of patients treated with valsartan and
25% of patients with other medications required a dose change at four weeks, due
to lack of response (p < 0.01). At week eight, 1.5% of patients with valsartan
and 17.4% of patients with other medications reported adverse effects such as
cough, headache, edema or flushing (p < 0.01). CONCLUSIONS: In this Chilean
observational multicentric study, valsartan proved to be more effective and to
cause less adverse effects than commonly used medications in hypertensive
patients.
PMID- 11008351
TI - [Variability determination in chromatin condensation and seminal alpha
glucosidase with relation with the spermiogram].
AB - BACKGROUND: Sperm functional tests as an addition to semen analysis have been
used to study the fertilization ability of spermatozoa. Besides the usual
variability of the seminal analysis an individual variability in the results of
functional tests has been recently found. AIM: To evaluate in a three months
period, the individual variability of sperm parameters and sperm maturation using
the chromatin condensation test and epidydime a-glucosidase (that allows to
discriminate obstructive processes). MATERIAL AND METHOD: The evaluation was
carried out in two donors (12 samples) apparently in good health. One of them
presented evident semen analysis alterations (donor 1) and the other was
considered normal under the WHO standards (donor 2). RESULTS: The averages for
donor 1 were: Sperm count 24 x 106 sperm/ml (range 10-58 x 106 sperm/ml),
morphology 31.8% (range 30-35%), total motility 33% (range 20-42%), sperm
maturation 38% (range 28-78%), a-glucosidase 8.65 (U/ml (range 5-10 (U/ml). The
averages for donor 2 were: Sperm count 96 x 106 sperm/ml (range 50-140 x 106
sperm/ml), morphology 32.2% (range 30-35%), total motility 69% (range 58-78%),
sperm maturation 17% (range 7-30%), a-glucosidase 36.9 (U/ml (range 20-82 (U/ml).
CONCLUSIONS: These results show that significant variations can be found in the
sperm parameters and in seminal plasma a-glucosidase; however these variations
are generally maintained at the normal or abnormal ranges for each individual,
except the sperm morphology that was constant and with low variation in both
donors. The determination of the chromatin condensation in the semen analysis
gives an additional information about the grade of sperm maturation and would be
of great value for differentiating between sperm samples that show similar
morphology values.
PMID- 11008352
TI - [Clinical and molecular characterization of autosomal recessive chronic
granulomatous disease caused by p47-phox deficiency].
AB - BACKGROUND: The cytosolic protein p47-phox (phagocyte oxidase) is one of the
essential components of the superoxide generating system in phagocytes and its
defect causes approximately 30% of the chronic granulomatous disease (CGD) cases.
AIM: Two patients were studied, belonging to the same family, without a
consanguinous background, in which deficiency or absence of superoxide generation
was found together with recurrent and severe infections in one case and benign
infections in the second. METHODS: The presence of gp91-, p67- and p47-phox in
patients and controls was determined by Western Blot analysis of granulocytes.
Sequencing of PCR amplified DNA was performed by an enzymatic method. RESULTS:
Western Blot analysis showed normal expression of gp91 and p67 and absence of p47
phox. The molecular genetic study demonstrated a homocygotic dinucleotide GT (GT)
deletion at the beginning of exon 2 of the p47-phox gene. The same mutation has
been found in European, American and Japanese patients. CONCLUSIONS: The
molecular characterization of this pathology done for the first time in Chile is
important for diagnostic classification, patient prognosis, and adequate genetic
advice and a possible future therapy.
PMID- 11008353
TI - [Treatment of hyperthyroidism with radioiodine: effects of administered dose on
complications and thyroid function].
AB - BACKGROUND: Radio-iodine is a definite therapy for Graves disease
hyperthyroidism. However, the optimal dosage is still debatable. AIM: To assess
the effects of different radioiodine doses on thyroid function and complications
in patients with hyperthyroidism. MATERIAL AND METHODS: A retrospective analysis
of 139 patients with hyperthyroidism, treated with ratio-iodine between 1988 and
1998. Radio iodine dose used was classified as low (< 10 mCi), intermediate (10
14.9 mCi) or high (> or = 15 mCi). RESULTS: Thirty-five patients were treated
with low doses, 33 with intermediate doses and 71 with high doses. There were no
differences between these patients in age, disease severity, frequency of post
treatment euthyroidism or complications. Patients treated with low doses had a
higher frequency of persistent hyperthyroidism than patients treated with high
doses (25.7 and 4.2% respectively, p < 0.001). Likewise, the frequency of
subsequent hypothyroidism was 60% in patients treated with low doses and 84.5% of
those with high doses, in whom it also appeared earlier. Associated complications
were clinically irrelevant. In seven patients, Graves ophthalmopathy progressed
after treatment, but this progression was not associated with the dose used.
CONCLUSIONS: Radio iodine in high doses is useful, safe and effective for the
treatment of Graves hyperthyroidism.
PMID- 11008354
TI - [Triple therapy of short-term with azithromycin, amoxycillin and omeprazole for
the eradication of Helicobacter pylori].
AB - BACKGROUND: The high cost and complexity of therapeutic schemes for the
eradication of Helicobacter pylori has stimulated the search of simpler and
cheaper treatment options. AIM: To evaluate the efficacy of 3 days of
azithromycin 500 mg od, 7 days of amoxycillin 750 mg tid and omeprazole, 20
(Group A) or 40 mg (Group B) on randomization, as a treatment for Helicobacter
pylori infection in patients with endoscopically diagnosed peptic ulcer. METHODS:
H. pylori status of peptic ulcer patients was pathologically confirmed by the
examination of five gastric biopsies using the Giemsa stain and by rapid urease
testing in two gastric biopsies. H. pylori status was reassessed not less than 28
days after completing treatment. Adverse events and compliance were evaluated.
RESULTS: Fifty four patients (29 men, 25 women, mean age 48 years) were enrolled,
28 in Group A and 27 in Group B. Per protocol the infection was cured in 58.8% of
patients (30/51; 95% CI: 45-73%). On an intention to treat basis, H pylori
infection was cured in 55%. Minor side effects including diarrhea and nausea were
reported by 32% of patients. Ninety-five per cent of patients consumed more than
95% of prescribed medications. H. pylori was successfully eradicated in 61% of
group A and 57% of group B patients (p = NS). CONCLUSION: Short term therapy with
azithromycin was poorly effective in curing H. pylori infection. The compliance
was excellent. Increasing Omeprazole from 20 to 40 mg/day did not improve
treatment effectiveness.
PMID- 11008355
TI - [BICAP tumor probe in the palliative treatment of malignant esophageal stenosis].
AB - BACKGROUND: BICAP tumor probe is a device that consists in an energy source and
olives that deliver bipolar electricity. It can be used for the fulguration of
esophageal tumors after endoscopic dilatation. AIM: To report the experience in
the treatment of malignant esophageal stenoses using the BICAP tumor probe.
PATIENTS AND METHODS: Patients with advanced esophageal tumors in aphagia, that
were not candidates for palliative surgery were included in this study. After
endoscopic dilatation, the tumor was fulgurated with the BICAP tumor probe.
RESULTS: Twenty one patients (nine male, aged 43 to 91 years old) were treated
with the device. A mean of 1.3 sessions with BICAP were necessary to obtain tumor
permeabilization, which was obtained in all patients. One patient died of
pneumonia 15 days after the procedure. All other patients were ingesting liquid
or semisolid diets after two months of follow up. Mean survival after the
procedure was 3.8 months. CONCLUSIONS: Electrical fulguration of esophageal
tumors is a valid therapeutic alternative in aphagic patients.
PMID- 11008356
TI - [Anorectal congenital malformations and their preferential associations.
Experience of the Clinical Hospital of the University of Chile. Period 1979
1999].
AB - BACKGROUND: Anorectal atresia is a relatively frequent malformation in the
newborn. According to the Latin American Collaborative Study for Congenital
Malformations (ECLAMC), its frequency is 4.1 per 10,000 born alive. AIM: To
determine the frequency of anorectal malformations at birth, and compare the
figures with those of other maternity hospitals in Chile participating in ECLAMC,
with the figures of the whole ECLAMC and with figures from other worldwide
monitoring systems. PATIENTS AND METHODS: All births occurred in the University
of Chile Clinical Hospital between January 1979 and August 1999, were reviewed.
RESULTS: During the study period, 70,242 children were born, 4,486 had a
malformation and 54 had an anorectal malformation (7.7 per 10,000 born alive).
Fifty nine percent had other associated malformations (of the urinary tract in
42.5%, skeletal in 26% and cardiovascular in 18.5%). Five stillborn babies had
other severe malformations. Twenty one children had a fistula. Forty three % were
male, 39% female and 18% had ambiguous sex. When compared with normal controls,
malformed newborns had a lower birth weight, lower gestational age and a higher
mean maternal age, a higher frequency of metrorrhagia during the first trimester
of pregnancy, a higher number of siblings with malformations and a higher degree
of consanguinity among parents. CONCLUSIONS: The participation of recessive genes
in the etiology of anorectal malformations is suggested.
PMID- 11008357
TI - [Nocardia asteroides infection in a patient with systemic lupus erythematosus].
AB - Nocardia asteroides infection are unusually observed in systemic Lupus
erithematous (SLE) patients. They are generally associated to steroidal and
immunosuppressive therapy. We report a 24 years old female with SLE diagnosed in
1994 who developed a severe preeclampsia in her first pregnancy requiring
emergency caesarean section. Post partum acute renal failure and type IV lupus
nephropathy were treated with hemodialysis, methylprednisolone, cyclophosphamide
and prednisone. Three months later, while she was receiving the fourth
cyclophosphamide dose, she presented with a pleuro pneumonia and occipital
abscess, both caused by Nocardia asteroides. She was treated with cotrimoxazole +
cefixime and pleural decortication was required. Five months later, she developed
Meningitis caused by Nocardia asteroides and hydrocephalus. She was treated with
ceftriaxone, vancomycin, cotrimoxazole and ventricular shunting procedure. Two
months later, a retroperitoneal abscess was diagnosed and surgically drained but
the patient died, due to a methicillin-resistant Staphylococcus aureus
septicemia.
PMID- 11008358
TI - [Traumatic rupture of thoracic aorta and non operative treatment of concomitant
splenic lesion. Case report].
AB - We report a 26 years old male that suffered a motorcycle accident resulting in a
traumatic aortic rupture and splenic laceration. He was subjected to a surgical
repair of the aortic lesion under complete heparinization. The splenic rupture
was non operatively managed successfully.
PMID- 11008359
TI - [Reflections on the current state of anatomic pathology in Chile].
AB - The present article reviews the most relevant aspects of the practice of Anatomic
Pathology in Chile. The importance of biopsy and autopsy are analysed, in
particular the consequences of the fall in the number of autopsies performed in
our hospitals, in the recent decades. The modern pathologist is confronted with
two situations: the renovation of the value of the autopsy and the acquisition of
new diagnostic technologies, both not usually considered in the classical
morphologic approach of Pathology. The ways to solve these problems in a
discipline that is still a fundamental specialty in modern medicine are analyzed.
PMID- 11008360
TI - [Tumorogenesis and mdm2 protein].
AB - Tumorogenesis is associated with several events by which a normal cell transforms
itself into a tumour cell with an increased proliferation rate. One of the most
important research initiatives in this area is the characterization of the
molecular mechanisms involved in tumorogenesis and cancer. Oncogenes and tumour
suppressor genes are directly involved in the cell cycle, differentiation, and
apoptosis. The cellular oncogene MDM2 seems to be abnormally elevated in several
human tumours, specially in sarcomas. The MDM2 gene product, mdm2 protein, pS3
and retinoblastoma (Rb) proteins, play crucial roles in the control of the cell
cycle. The molecular interactions between mdm2, pS3 and Rb in cancer, are
associated with a loss of control in the G1 phase of the cell cycle leading to
uncontrolled cell proliferation. Studies by gene amplification appear to show an
incomplete picture of mdm2 protein levels in tumour cells. The simultaneous
determination of mdm2 protein and mRNA levels seems to give a more accurate
interpretation of the abnormal function of the mdm2 protein. Thus, in addition to
gene amplification, different mechanisms by which mdm2 is overexpressed in cancer
cells also play an important role in tumorogenesis.
PMID- 11008361
TI - [The terminally ill patient. Grupo de Estudios de Etica Cliinica de la Sociedad
Medica de Santiago].
AB - The classification of a patient as terminally ill is based on an expert diagnosis
of a severe and irreversible disease and the absence of an effective available
treatment, according to present medical knowledge. Terminal diseases must not be
confused with severe ones, since the latter may be reversible with an adequate
and timely treatment. The physician assumes a great responsibility at the moment
of diagnosing a patient as terminally ill. The professional must assume his care
until the moment of death. This care must be oriented to the alleviation of
symptoms and to provide the best possible quality of life. Also, help must be
provided to deal with personal, legal and religious issues that may concern the
patient.
PMID- 11008362
TI - [Evidence based medicine].
PMID- 11008363
TI - The testicular descent in human. Origin, development and fate of the gubernaculum
Hunteri, processus vaginalis peritonei, and gonadal ligaments.
AB - Testicular descent has to be divided into the turn-out of the testis and
epididymis from the abdomen proper and an inner abdominal descent of genital
organs. Both events are closely related to and depend on the development and
reorganisation of ligaments, mainly the gubernaculum Hunteri. These seemingly
unambiguous events are controversially described since the first description of
the gubernaculum, and results and specifics of other species were intermingled
with data from humans, thus giving more confusion than lucidity in this important
step of gonadal development. Here, we concentrate on human embryos,
chronologically investigated by serial sections, scanning electron microscopy,
three-dimensional reconstructions, microdissection and immunohistochemistry. The
first question to be answered was whether a real inner descent of gonads occurs.
We demonstrated this inner descent by showing the relations of the gonads,
mesonephros, cranial mesonephric ligament and the anlage of the diaphragm with
the vertebral segments. No explosion-like increase in certain vertebral segments
was observed which might simulate a gonadal descent. The inner descent is coupled
with the growth of the gonad (ovary or testis), the involution of mesonephros,
the descending septum transversum or the anlage of the diaphragm, and the
intercalated cranial mesonephric ligament. This ligament always inserts medially
at the border between the gonad and mesonephros in close relationship to the
abdominal ostium of the mullerian duct, a region where hydatides often occur. In
contrast to the testes, the ovaries arrive very early--20-25 mm CRL--at their
definitive position of S2/3 (level of linea terminalis pelvis), yet, are
transversally oriented. The cranial gonadal ligament does not exhibit notable
increase in length during inner descent. It does not contain blood vessels. While
regressing in both sexes, it will be replaced by the plica formed by the ovarian
vessels, that is the suspensorium ligament of the ovary as known in adults. The
second point to be investigated was the origin, development, structure and fate
of the gubernaculum Hunteri as well as the processus vaginalis peritonei. Their
arrangement and composition is crucial for testicular descent. We discriminated
five phases of their development and differentiation. Phase I characterises the
early development of the gubernaculum of stage 14 CC (5-7 mm CRL) embryos. It
arises as conus inguinalis and connects the abdominal wall lateral to the
umbilical artery with the caudal part of the mesonephric fold. It is in this
early stage that the localisation of the inner inguinal ring is defined. In phase
II, stage 20-23 CC (21-30 mm CRL), three parts of the gubernaculum--abdominal,
interstitial and subcutaneous--can be distinguished. The processus vaginalis
peritonei appears with its dorsal layer firmly adhering to the ventral side of
the gubernaculum. The gubernaculum inserts cranially into the mesenchyme of the
genital ducts at their crossing-over. Opposite to it, but at some distance, a
ligament connects the caudal pole of the testis with the dorsal mesenchyme of the
genital ducts. In female embryos, the analge of the ovarian ligament appears as a
U-shaped, double peritoneal fold. Phase II is subdivided in phase IIa (32-55 mm
CRL), characterised by an enormous increase in length and volume of the
gubernaculum and also an enlargement of the processus vaginalis peritonei. In
phase III, sex-specific differences in gonadal position and gubernacular
structure can be observed for the first time. Testes increase in volume and come
close to the mesenchyme of the genital ducts. The caudal pole of the testis
overlaps both ducts. We also subdivide this phase into phase IIIa (about 100 mm
CRL) where two very important events occur in male foetuses: 1, the swelling of
the gubernaculum, and 2, the gliding of the testis across the genital ducts. This
gliding is permitted by both, the regression of the mullerian duct and t
PMID- 11008364
TI - [The claw of the domestic cat (Felis catus)--analysis of its shape].
AB - The feline claws in the forepaw and hind paw are very different in shape. An
objective method of comparison will be described. The differences in function and
the factors with regard to the shape are discussed.
PMID- 11008365
TI - Characterization of the swimming muscle of the anchovy Engraulis anchoita (Hubbs
and Martini 1935).
AB - The lateral muscle characteristics of individual female anchovies (Engraulis
anchoita) were studied by histochemical and ultrastructural techniques. Red, pink
and white fibres were discerned on the basis of the activity of the metabolic
enzymes succinic dehydrogenase, phosphorylase and myofibrilar ATPase, and the
usage of Sudan and periodic-acid Schiff staining techniques. Red fibres were
located at the surface, white fibres deep inside and pink fibres in between. The
red fibres appeared flattened or ribbon-shaped in transverse section and they
were located in rows separated by myosepta of connective tissue. The red and pink
fibres were multi-innervated whereas the white fibres were terminally innervated.
The relative proportion of the red muscle increased toward the caudal region, the
white muscle diminished toward that region, whereas the proportion of pink muscle
did not vary according to region, being scarce throughout. The distribution of
capillaries was also investigated, and as a result, the vascular supply proved to
be scarce in both white and pink muscle.
PMID- 11008366
TI - [Representation of the nerves of the wing of psittacines (Amazon, gray parrot}
using a digital photographic technique].
AB - In four blue-fronted Amazon and five African grey parrots, the nerves innervating
the muscles of the wings were carefully dissected and described. The preparation
steps were recorded with a digital camera. This technique has now advanced so far
that the image quality is almost the same as that of a normal camera. The
pictures are stored in a computer. They can be enhanced and published via the
Internet.
PMID- 11008367
TI - Effects of retinoic acid exposure in utero on mouse vibrissal follicle
development.
AB - It is known that topical all-trans-retinoic acid (RA) modulates growth and
differentiation of skin and its cutaneous appendages. To examine whether a pre
natal exposure to a potentially non-teratogenic dosage of all-trans-RA had any
effect on vibrissal follicle development, the histologic and immunohistochemical
responses to RA during its morphogenesis in NMRI mouse were investigated. After a
single oral dose of 30 mg/kg body weight of all-trans-RA on day 11.5 of
gestation, no fetal malformations were detected and the histological features and
the distribution of keratin (K) proteins in comparable stages of vibrissal
development were similar for the untreated, vehicle-treated and RA-treated mice.
The absence of teratogenic response and of adverse effects on the vibrissae under
the experimental conditions indicates that this protocol may be useful for
investigation of the effects of pre-natal exposure to RA on the post-natal
development of experimental tumours in the mouse skin.
PMID- 11008368
TI - Histochemical and morphometric aspects of the lateral musculature of different
species of teleost marine fish of the Percomorphi order.
AB - Cross-sections of the lateral musculature of 19 species of teleost fish of the
Percomorphi order were studied histochemically and morphometrically. The red,
pink and white muscles were observed in all the species except in Seriola
dumerilii and Scomber japonicus, in which no pink muscle was found. The red
fibres were the smallest due to their minimal diameters. Histochemically and
according to their location at least five types were found in the same species:
typical red, in rosette, of the border, infiltrated pink and in mosaic. The pink
fibres were larger than the red but smaller than the white. The form and
disposition of the pink muscle varied according to the species. This muscle is
made up by fibres of medium size, moderate m-ATPase and intermediate oxidative
activities. Their histochemical properties change near red and white muscles,
where they acquire the histochemical characteristics of the typical red fibres or
the low m-ATPase activity of white fibres, respectively. The white muscle is the
widest muscular layer. All of the species, except Thalassoma pavo are made up by
three fibre types (small with high m-ATPase activity, medium with moderate m
ATPase activity, and large with low m-ATPase activity). They are mixed and show a
histochemical and morphometric mosaic form. The extent of this mosaic depends on
the species. In most of the analysed species it was observed in areas close to
the pink muscle, but in three of them (Liza aurata, Seriola dumerilii and Coris
julis) it occupied all of the myotome.
PMID- 11008369
TI - Megakaryocytes and platelets in the spleen of the dromedary camel (Camelus
dromedarius).
AB - This study was carried out on spleens of clinically healthy camels (n = 35) of
both sexes (0.5-15 years) by routine histology, electron microscopy and
immunohistochemistry using 12 anti-bovine platelet antibodies. Megakaryocytes
were observed in the red pulp. Their number decreased with age: they were found
in the spleens of all camels under 8 years old but only in 57% of camels over 8
years old. Only two antibodies (IVA37 and IVA38) cross-reacted with camel
platelets. A large number of platelets were found in the splenic cords and the
marginal zone. Ultrastructurally, the platelets were oval in shape surrounded by
a plasma membrane, and their cytoplasm was rich in glycogen and contained less
dense granules. Microtubules and microfilaments were found at their periphery.
Several platelets were observed in the red pulp. There are similarities in some
surface antigens of bovine and camel platelets. The presence of megakaryocytes in
the camel spleen indicates a thrombopoietic function of the spleen until
adulthood but that this decreases with age thereafter.
PMID- 11008370
TI - Growth-promoting effects of different fractions of extra-embryonic coelomic fluid
on embryonic development.
AB - In the early stages of embryonic development, many growth-promoting molecules
must be provided by the maternal system. These factors may be supplied locally to
the embryo, by the decidua, the placenta, or the yolk sac. In this study the
growth-promoting potential of extra-embryonic coelomic fluid (EECF) and its
fractions was investigated. The embryonic requirement of growth-promoting
molecules may be studied by reducing the growth-supporting capacity of serum.
Thus, ultrafiltration of rat serum was carried out for 8 h using Millipore
filters with a molecular weight exclusion of 30 kDa. Rat embryos at 9.5 days of
age were cultured for 8 days for anembryonic yolk sacs, and then EECF was
collected and divided into three different molecular weight fractions by
ultrafiltration. Rat embryos were cultured for 48 h in whole rat serum and the
serum retenate (which has low growth-supporting capacity) in the presence and
absence of EECF, its fractions, or in EECF only. Embryos grown in retenate showed
severe growth retardation, and the addition of EECF significantly improved
embryonic growth. The fraction which contained the molecules with molecular
weight between 10 and 30 kDa had significantly more effect on embryonic
development than the other fractions. This fraction of EECF was analysed by gel
electrophoresis. Three of the four protein bands observed in this fraction were
identified by amino-terminal sequencing as alpha-fetoprotein precursor (22 kDa),
apolipoprotein A1 precursor (24 kDa) and fetal haemoglobin Y2 chain (14 kDa),
none of which are likely to be responsible for the growth-promoting activity. To
further investigate growth-promoting proteins, EECF was Western-blotted to
nitrocellulose membranes and probed with antisera against rat prolactin,
epidermal growth factor, insulin-like growth factors I and II and human placental
lactogen. No immunoreactive bands were detected in the EECF, suggesting that
either these proteins are not present or are present at levels too low to be
detected. Although the growth-promoting effect of the EECF was demonstrated in
this study, the molecules responsible remain uncharacterized.
PMID- 11008371
TI - Temperature effect on muscle growth of the axial musculature of the sea bass
(Dicentrarchus labrax L.).
AB - In order to determine the temperature effect on the axial muscle growth of sea
bass, a stock of larvae was subjected to the following incubation and cultivation
temperatures, respectively: 15 degrees C/ambient, 15/17 degrees C, 17 degrees
C/ambient and 17/17 degrees C. In all groups the cross-sectional area of white
and red muscles and the number and average area of the white and red muscle
fibres were quantified. Results showed that the embryonic period, pre-larval
phase and the end of metamorphosis were accelerated at higher temperatures.
During the endogenous feeding period, muscle growth took place by fibrillar
hypertrophy, and was not influenced by the temperature. Thereafter (external
feeding) muscular hyperplasia began, and growth of all the muscular parameters
was favoured by the effect of high incubation and cultivation temperatures, with
the latter having higher influence. High incubation temperature had an slight
effect on muscle growth and body length, which was only observed from 15 days.
Metamorphosis finished at 3 +/- 0.4 cm in all the larvae, but this length was
earlier reached at higher temperatures. At 120 days, the largest growth was
obtained in the larvae maintained at a higher temperature.
PMID- 11008372
TI - On the morphology of the liver in the two-humped camel (Camelus bactrianus).
AB - The liver of a two-humped camel (Camelus bactrianus) was examined by means of
gross anatomy and histology. The liver appeared characteristically as an enlarged
triangle in visceral aspect, and showed the following lobation: the left lateral
and medial lobes, the right lobe, the caudate lobe and the quadrate lobe. These
findings were similar to those for the one-humped camel. Histologically, a
distinct lobulation, a typical arrangement of the interlobular connective tissue,
and the trias was confirmed.
PMID- 11008373
TI - Has active immunization against gonadotrophin-releasing hormone any effect on
testis innervation in the pig? An immunohistochemical study.
AB - The innervation of porcine testes was studied in intact animals and in boars
undergoing active immunization against gonadotrophin-releasing hormone (GnRH) by
means of immunohistochemistry using antibodies to tyrosine hydroxylase (TH),
dopamine beta-hydroxylase (D beta H), vasoactive intestinal polypolypeptide
(VIP), neuropeptide Y (NPY), synaptosome-associated protein of 25 kDa (SNAP-25)
and protein gene product 9.5 (PGP 9.5). Moreover, the distribution of luteinizing
hormone (LH) receptors in clusters of Leydig cells was also investigated. To
identify these cells easily, either the NADPH-diaphorase histochemical technique
or the Mayer counter-staining procedure was applied. Differences in the
distribution pattern and relative density of particular subsets of
intratesticular nerve fibres were observed in immunized boars as compared to
those found in the intact animals. In the testes of non-treated animals, only
single TH-immunoreactive (TH-IR) nerve fibres were observed. However, many D beta
H-IR nerve terminals surrounded blood vessels in the tunica albuginea and
parenchyma. Very scarce VIP-IR nerves occurred only in the tunica albuginea,
mainly in close vicinity to blood vessels. Immunoreactivity to NPY occurred in
single nerve fibres. Immunoreactivity to SNAP-25 and PGP 9.5 was found in single
nerve fibres distributed mainly in the tunica albuginea. The interstitial cells
were heavily stained for LH-receptors and NADPH-diaphorase. In the testes of
immunized animals, only single TH-IR nerve fibres, scattered mainly in the tunica
albuginea, were observed. Some TH-IR nerve terminals were also encountered in the
parenchyma of the organ, where they were always associated with blood vessels. D
beta H-IR nerve fibres formed a dense network distributed throughout the testis
in association with the capsule, vasculature and interstitium. Some fibres were
observed to run between seminiferous tubules. VIP-IR nerve fibres were located in
the neighbourhood of blood vessels in the tunica albuginea and parenchyma. Only
single VIP-IR nerves were found between seminiferous tubules. Numerous NPY-IR
nerve fibres occurred in the tunica albuginea and parenchyma of the organ. SNAP
25-IR and PGP 9.5-IR nerve terminals formed a dense network distributed
throughout the testis and many fibres were observed between seminiferous tubules.
Interstitial cells were very weakly stained for LH receptors or NADPH-diaphorase.
PMID- 11008374
TI - beta-Lactam derivatives as enzyme inhibitors: 1-peptidyl derivatives of 4
phenylazetidin-2-one as inhibitors of elastase and papain.
AB - N-Peptidyl substituted azetidin-2-ones were synthesized and evaluated as
inhibitors of the serine protease elastase, and the cysteine protease papain. All
compounds were synthesized from 4-phenylazetidin-2-one, either from the racemate
or from the pure enantiomers. The (S)-enantiomer was prepared by enantioselective
synthesis from (S)-beta-phenyl-beta-alanine, while the (R)-enantiomer was
obtained by enzymatic resolution with alpha-chymotrypsin. N-Alkylation with
bromoacetates introduced a spacer group which, after hydrolysis to the free acid,
was acylated with amino acid esters or di- or tripeptide esters. The enzymatic
assays proved some derivatives to be effective inhibitors of PPE and/or papain. N
BOC protected amino acid derivatives without a spacer group inhibited PPE
reversibly, while derivatives with spacer group showed either weak or no
inhibitory properties. On the other hand, papain was inactivated irreversibly by
ethyl (RS)-2-oxo-4-phenylazetidin-1-acetate. The highest inhibitory activity
against papain was found for the diastereomers of N-(2-oxo-4-phenylazetidin-1
acetyl)-L-alanyl-L-valine benzyl ester, a compound with a spacer group.
PMID- 11008375
TI - A qualitative model for the histamine H3 receptor explaining agonistic and
antagonistic activity simultaneously.
AB - A pharmacophore model for histamine H3 ligands is derived that reveals the
putative interaction of both H3 agonists and antagonists with an aspartate
residue of the receptor. This interaction is determined by applying the density
functional theory implemented in a program package adapted for parallel
computers. The model reveals a molecular determinant explaining efficacy as the
conformation of the aspartic acid residue differs according to whether it is
binding to agonists or antagonists. The differences in structure-activity
relationships (SAR) observed for the lipophilic tails of different classes of H3
antagonists are now explained, since the model reveals two distinct lipophilic
pockets available for antagonist binding.
PMID- 11008376
TI - Synthesis and anticonvulsant activity of acetylenic quinazolinone derivatives.
AB - Acetylenic derivatives of quinazolinones and quinazolinediones were synthesized
and evaluated for their anticonvulsant activity. Most compounds displayed seizure
antagonizing activity in the maximal electroschock test (MES test) in most cases
associated with little or no acute neurotoxicity determined in the rotorod test.
Only three compounds exhibited significant activity in the seizure threshold test
with subcutaneous pentylenetetrazole (scMet test). Based on the ED50 in the MES
test, 1,3-bis-(prop-2-ynyl)-quinazoline-2,4-(1H,3H)-dione(9a) was about ten-fold
less active than phenytoin or carbamazepine but about as active as mesuximide.
PMID- 11008377
TI - A novel series of 2-carboxytetrahydroquinolines provides new insights into the
eastern region of glycine site NMDA antagonists.
AB - A series of potent 4-substituted tetrahydroquinolines has been synthesized and
biologically tested in order to refine the eastern region of the pharmacophore
model for glycine site NMDA antagonists concerning the assessment of
lipophilicity, flexibility, and hydrogen bonding. Displacement studies on rat
cortical membranes using [3H]-5,7-dichlorokynurenic acid as a radioligand
indicated that binding affinities are markedly enhanced when additional hydrogen
accepting groups are introduced into the eastern region of the 2
carboxytetrahydroquinolines. Among the most potent ligands were some urea,
sulfonylurea, and crown ether compounds as interesting leads for new diagnostics,
especially for the evaluation of PET tracers, which allow biodistribution studies
and NMDA receptor studies in the living organism.
PMID- 11008379
TI - Training. A key issue for the future of general practice.
PMID- 11008378
TI - A new flavonoid from Limonium axillare.
AB - A new flavonol glycoside identified as myricetin 3-O-beta-D-sorboside (1) has
been isolated from the leaves of L. axillare. The new compound showed a moderate
inhibition of Ehrlich ascites carcinoma cells.
PMID- 11008380
TI - Aboriginal health. Can leadership and innovation make a difference? Part 2.
PMID- 11008381
TI - Medial forefoot pain.
PMID- 11008382
TI - Not every child who coughs has asthma.
PMID- 11008383
TI - Irritable bowel syndrome. Practical management.
AB - BACKGROUND: Irritable bowel syndrome (IBS) is a common problem affecting one in
six Australians. In any patient complaining of chronic or recurrent abdominal
pain, chronic diarrhoea or constipation or bloating, IBS should top the list of
possibilities. OBJECTIVE: To outline an approach to the practical management of
patients with IBS. DISCUSSION: A positive diagnosis can be made if a few simple
questions are asked, and the diagnosis can be confirmed by a small number of
tests to exclude structural disease. Improved understanding of the differences in
gut function in patients with IBS is likely to result in the development of some
exciting new therapies.
PMID- 11008384
TI - Rectal bleeding.
AB - BACKGROUND: Rectal bleeding, although common, is frequently alarming to patients
because of its association with bowel cancer. An understanding of the causes of
rectal bleeding and a systematic approach to diagnosis provides the basis for
preventive measures and appropriate treatment. OBJECTIVE: This article discusses
the causes, history, examination and investigation of rectal bleeding according
to the age of the patient. Treatment of the various conditions is outlined.
DISCUSSION: Although haemorrhoids are the commonest cause of rectal bleeding,
most patients over 40 years old presenting with this symptom require colonoscopy
in order to screen for and treat premalignant polyps and colorectal cancer.
PMID- 11008385
TI - Coeliac disease. Update 2000.
AB - BACKGROUND: Coeliac disease is increasingly recognised as a cause of nutritional
disturbance in the Australian community. Diagnosis may be delayed because the
presentation is highly variable. OBJECTIVE: To outline an approach to diagnosis
and management of coeliac disease. DISCUSSION: Newer, more specific serological
testing is helpful in screening asymptomatic individuals but endoscopic small
intestinal biopsy is required for diagnostic certainty. A gluten free diet
induces remission but not cure. Lifelong adherence reduces the risk of
complications, including malignancy. All patients diagnosed with coeliac disease
require expert dietetic assessment and counselling and all should be encouraged
to join their state Coeliac Society. Excellent internet based sites now offer
appropriate information for patients and their families.
PMID- 11008386
TI - Anal fissures.
AB - BACKGROUND: Anal fissures are common conditions, presenting with bleeding,
itching, and pain of varying severity. Pain and bleeding is frequently attributed
to haemorrhoids, which may delay commencement of appropriate therapy. Other
causes for bleeding must also be excluded, with investigations taking into
account the clinical findings and the age of the patient. OBJECTIVE: To discuss
the pathogenesis and management of anal fissures. DISCUSSION: Recent studies have
changed our understanding of the pathophysiology of anal fissures. It is now
known that the majority of fissures are caused by internal sphincter spasm and
resulting in ischaemia of the anal mucosa. Pharmacological agents that relax the
sphincter have provided a novel approach to treatment, allowing surgery to be
avoided in some patients.
PMID- 11008388
TI - Casting acute fractures. Part 1--Commonly asked questions.
AB - BACKGROUND: Correct splinting of acute fractures offers comfort and is often the
definitive treatment for many simple injuries. The use of a cast is a common
method of splinting. The best methods for application of casts and their
rationale are poorly understood by many doctors and not detailed well in standard
texts. OBJECTIVE: This series will attempt to address some common initial casting
techniques suitable for general practice. Specific time and cost saving
manoeuvres will be given. Common pitfalls will be identified. DISCUSSION: The
primary care physician traditionally applies the first cast. This coincides with
the time of greatest risk as fractures are potentially unstable, and swelling is
often anticipated rather than actually present. The swelling and associated
morbidity from a cast can be considerable. Optimising comfort, function and
safety in the initial cast is multifactorial. Attention to these factors gives a
far better short and long term outcome for the patient. This also reduces
medicolegal risk and the cost of unplanned return visits due to unnecessary
morbidity.
PMID- 11008387
TI - COX-2 inhibitors. What is their place?
AB - BACKGROUND: Nonsteroid anti-inflammatory drugs (NSAIDs) are widely used in
Australia for the treatment of arthritis and the relief of pain. However, side
effects, particularly those affecting the gastrointestinal tract, are of
considerable cost to the individual and the community. OBJECTIVE: To examine the
role of selective cyclo-oxygenase-2 (COX-2) inhibitors in the anti-inflammatory
armamentarium. DISCUSSION: COX-2 inhibitors are of similar clinical efficacy to
nonselective NSAIDs. They cause significantly fewer endoscopic ulcers, but these
lesions are usually clinically asymptomatic. Dyspepsia rates are 1-2% lower. The
frequency of serious gastrointestinal complications (symptomatic ulceration,
bleeding, perforation) appears to be reduced by 0.5-1.0%. As these problems occur
infrequently, routine use of COX-2 inhibitors would not be cost effective.
Although no data are yet available, patients at high risk of NSAID induced
gastrointestinal complications may be the group for whom COX-2 inhibitors will
provide most clinical benefit.
PMID- 11008389
TI - Patient education. Caring for your plaster.
PMID- 11008390
TI - Acute sore throat and bronchitis. How effective are antibiotics?
PMID- 11008391
TI - Sudden loss of vision in an elderly woman.
PMID- 11008392
TI - Sudden onset of breathlessness. What are the possibilities in the pregnant
patient?
PMID- 11008393
TI - Midfoot pain.
PMID- 11008395
TI - Screening for bilharzia.
PMID- 11008394
TI - Pulmonary embolism.
PMID- 11008396
TI - To be or not to be. Evidence in support of contemplative practices--Part 1.
PMID- 11008397
TI - Is it all black magic?
PMID- 11008398
TI - Methodological/ethical issues and general practice research.
PMID- 11008399
TI - The end of full time general practice.
PMID- 11008400
TI - Chinese attitudes to institutional care of their aged. A study of members from
the Chung Wah Association, Western Australia.
AB - OBJECTIVE: To examine Chinese attitudes to institutional care of their aged and
to identify the factors that influence these attitudes. METHOD: A cross sectional
survey of 815 randomly selected members of the Chung Wah Association, Western
Australia was undertaken in 1997 using a mailed self administered questionnaire.
The survey instrument was developed through a literature review, interviews and
pilot testings and consisted of categorical and noncategorical items. The data
were analysed using the SAS (V 6.12) software package. Factor analysis, logistic
regression and Chi-square analysis were used on the data. The statistical
significance level was set at p < or = 0.05. RESULTS: A total of 431 (53%)
completed responses were received. The study showed that 86% of the respondents
agreed that the disabled elderly should be institutionalised. Age contributed
mainly to the respondents' attitudes to institutionalising the disabled elderly,
while the respondents' sex, education, occupation, country of origin and length
of residence in Australia did not. Social responsibilities together with the
health factors of the elderly had important effects on these attitudes. About 55%
of respondents agreed that their Chinese culture influenced their attitude. Only
21% of the respondents agreed that the nondisabled elderly should be
institutionalised, 54% disagreed, while 24% remained neutral. Respondents who
were likely to institutionalise their disabled elderly were also unlikely to live
with their children when they became disabled. A majority of respondents were in
favour of government funding of institutions and care givers of the elderly.
CONCLUSION: The study provided several important observations and information for
health planners and general practitioners to identify the aged at risk of
institutionalisation and make arrangements for community support for effected
families so that the aged can be encouraged to remain with their families.
PMID- 11008401
TI - Are part timers real GPs? Attitudes of general practitioners toward those who
work part time.
AB - BACKGROUND: Current attitudes within the medical profession suggest that one
cannot be a 'real' doctor unless one works full time. The aim of this study was
to determine the views and attitudes of a sample of GPs toward part time
practice. METHOD: As part of a larger study, GPs in two divisions in metropolitan
Melbourne were sent a questionnaire based survey. GPs were asked to rate
statements about part time practice using a Likert scale. RESULTS: The response
rate was 55% (n = 246). The majority of GPs disagreed with the statement 'part
time GPs are not real GPs' but feelings were mixed about whether part timers
covered the same range of clinical content as full timers. One fifth of
respondents questioned the competence of part time GPs. Male GPs, those over 55
years and full timers were more likely to hold negative views toward part time
general practice. DISCUSSION: Our results show a 'generational' pattern toward
part time practice. With the increasing numbers of women entering general
practice, these attitudes will need to change to accommodate the fact that more
GPs will be choosing to work part time in the future.
PMID- 11008402
TI - Publicly-funded influenza and pneumococcal immunization programs in Canada: a
progress report.
PMID- 11008403
TI - [Bases and future perspectives of oncologic surgery in the integral treatment of
advanced neoplasms].
PMID- 11008404
TI - [Neoadjuvant chemo-radiotherapy in the treatment of rectal cancer: preliminary
results].
AB - Many studies in the literature have confirmed the role of combined therapy in the
treatment of rectal neoplasms. Aim of the Authors' study was to evaluate the
efficacy of preoperative neoadjuvant radiochemotherapy in these patients. The
study group consisted of 15 patients, affected by rectal adenocarcinoma T < 4 M0
with age < 75 years, observed from January to August 1998, who underwent to RT of
pelvis with three fields--total dose 32 Gy- in ten days associated with 5 FU(500
mg/m2) during the first five. After restaging the patients were operated on.
Anterior resections (AR) were followed by mechanical colorectal anastomosis in 10
patients, coloendoanal anastomosis in 4, while in 1 case an abdominoperineal
resection (APR) was performed. The protocol was well tolerated in every patient
and perioperative complications were similar to those in the control group. A
considerable reduction of the mass was obtained in a great percentage of patients
studied, confirmed by pathologic examination like "down staging" of cancer. In no
case a complete response to the therapy was observed (pT0N0). Survival in the
patients operated on for rectal adenocarcinoma in about 50% and local relapse is
the most important site of recurrent disease. The aim of neoadjuvant protocol is
the control of lymphatic spread and reduction rectal neoplasm allowing coloanal
anastomosis in the treatment of the 1/3 inferior rectal cancer. Literature data
confirm a significant decrease of local relapse, probably with a better survival.
The Authors study confirms that combined preoperative therapy is well tolerated
in most of the cases and it represents the protocol of choice in the patient
affected by rectal cancer.
PMID- 11008405
TI - [Guidelines for routine assessment of cardiologic surgical risk:
electrocardiogram].
AB - Cardiac complications are the main cause of perioperative mortality. A
preoperative electrocardiogram and cardiologist's consultation are usually
performed to get information about cardiac state of patients undergoing surgery
and to prevent complications. In their study the Authors applied to 1715 patients
undergoing surgery an evaluation schedule for the cardiac surgical risk,
including an ECG as first-level test, performed systematically on the whole
sample. The aim was to assess predictive value of this preoperative examination
to verify its efficacy as routine test. Basing on results achieved,
electrocardiogram is not routinely indicated before noncardiac elective surgery,
but it should be requested for the patients having high risk of cardiac
complications at an accurate clinical-anamnestic examination. Therefore, clinical
judgement, that is the first level of any preoperative evaluation, should be the
basis for ordering an ECG to be considered a second-level test.
PMID- 11008406
TI - [Isolated cystic cervical lymphatic metastasis from occult papillary carcinoma of
the thyroid: unusual and rather difficult diagnosis].
AB - Thyroid papillary carcinoma, exceptionally, can appear with cervico-lateral
metastases in absence of thyroid evident disease. In that case we can have an
infected branchial cyst, therefore is very important a correct preoperative
diagnosis with FNAB. In literature were described 30 cases of cervico-lateral
cystic masses that the histology revealed as occult papillary carcinoma
metastases. Our experience is about 80 cases of papillary carcinoma, in only 2
cases the cancer was evident as a tight-elastic tumour in cervico-lateral region,
hypoechogenic to the US scan with irregular and thick wall: one of the patient
had multinodular goiter; the other one didn't have clinical of US scan character
of thyroid disease. FNAB on lymph nodes shows doubtful cells evidence. Both
patient had a total thyroidectomy with functional cervico-lateral and MAS
lymphadenectomy. In one patient histology showed a papillary carcinoma of 4 mm in
the right lobe, in the other patient the cancer was unknown. FNAB, in all
doubtful cases, is the most important diagnosis test.
PMID- 11008407
TI - [Surgical treatment of arterial hypertension: experience and results].
AB - Hypertension is a wide spread disease. In a small percentage of cases
(nephrosclerosis, renovascular hypertension, endocrine hypertension) surgical
treatment could be resolutive. The Authors describe their experience of the last
five years about the subject, emphasize the technical detail taken and the
results achieved; they outline the necessity to give the indications for surgery
in wise manner considering clinical, laboratory and instrumental findings.
PMID- 11008408
TI - [Total versus subtotal thyroidectomy for multiple node goiter: experience with
350 surgically treated cases].
AB - The surgical treatment of benign thyroid pathology and in particular the
multinodular form is controversial. This controversy exists and one must choose
either perform conservative surgical therapy such as lobectomy or sub-total
thyroidectomy or total thyroidectomy. From January 1985 to July 1999, the Authors
observed 534 cases of benign thyroid pathology. Of these 534, 330 were diagnosed
with primitive goiter, and 20 with recurrent goiter; 13 cases of the primitive
goiter type were found to have microfoci of carcinoma inside the goiter on the
definitive histologic exam. There were 275 patients who underwent total
thyroidectomy and the remaining 75 cases with ultrasound proven multinodular
goiter were treated with lobectomy or sub-total thyroidectomy, depending on the
appearance at the time of the operation as well as the macroscopic and
microscopic exams of the integrity of the glandular parenchyma performed while in
the operating room. The Authors demonstrated that in multinodular goiter there is
a high percentage of cases with disease involving the entire gland. Many areas of
apparently healthy tissue are found to be microscopically involved with a
variable grade of chronic lymphocytic thyroiditis or follicular hyperplasia or
even lobular dysplasia with the tendency to form nodules. These signs of disease
of this organ tend to recur if not treated.
PMID- 11008409
TI - Neck hibernoma: case report and literature review.
AB - The case history of a 23 year old man with a large hibernoma of the cervical
region is reported. Th tumour showed all the clinical and pathologic
characteristic of these rare benign neoplasms. A review of the most recent
literature supports the Authors' conclusion that local excision is curative.
PMID- 11008410
TI - [Diaphragm rupture caused by closed trauma. A more and more frequent condition].
AB - The Authors report a case of rupture of the diaphragm in blunt trauma of the
abdomen, to examine the more significant features of this condition whose
incidence proves to be increasing, after a review of the literature data,
parallel to the increase of accidents on the road and at work. They examine the
most important pathogenic problems and these related to the mechanism leading to
diaphragmatic lesion and they highlight the deeper pathophysiological changes
suffered from the patient with such a condition. They draw attention to what they
consider to be the most important aspect, and therefore the diagnosis. In fact,
in accordance with the various series of cases reported in the literature, it is
crucial in the diagnostic problem is when the possible cause of the rupture is
suspected and necessary diagnostic cascade (Rx, echotomography, TC) is activated
so to highlight the lesion. Therefore a quick diagnostic fitting is necessary for
the survival of the acute patient with hernia of the thorax cavity, as well as
quick surgical correction of the lesion that, as in the case described, serves to
achieve the best possible anatomic-functional results.
PMID- 11008411
TI - [Gastric epithelial dysplasia].
AB - Gastric epithelial dysplasia represents the only true histological marker of
gastric cancer. In this bringing up to date, such subject is reproposed in
consideration of taking into account the most recent acquisitions, subdividing
gastric dysplasia into two degrees only: moderate and severe. For the first time
an immunophenotypic study is made by means of the evaluation of gastric-entero
pancreatic antigens, which better identify the evolutive potential of the two
degrees of gastric dysplasia and, furthermore, the clinical development is
evaluated, thus showing the necessity of a strict endoscopic surveillance of such
lesion.
PMID- 11008412
TI - Correlation between cytochrome P-450 system and liver function tests during
experimental liver transplantation.
AB - The aims of this investigation are: 1) to assess the function of the hepatocyte
in transplanted porcine liver, immediately after reperfusion, by monitoring both
LFTs and the MEGX levels; 2) to search for correlation between MEGX and LFTS, in
an effort to evaluate the metabolic mechanisms occurring in the early liver
transplantation revascularization phase. The MEGX test was found to be less than
50 micrograms/ml in all the recipients and all the LFTS tested have been reported
to be out the normal range. Furthermore our data has shown a statistically
significant correlationship between the MEGX values and those of alkaline
phosphatase and prothrombin and a highly significant correlationship with
cholinesterase.
PMID- 11008413
TI - [Surgical indications in pulmonary tuberculosis].
AB - Since the begin of the century, the surgery for treatment of pulmonary
tuberculosis showed an important evolution. The procedure has proved to be useful
in the 20% of patients. It appears that the percentage is drug-resistant or
complicated. The authors describe their experience in the years from 1992 to 1997
and, in accordance with the literature in this field, outline the good prognosis
to 5 years, with a percentage of 90-96% of non-infected patients. Very important
is the time of surgical intervention, the compliance of the medical treatment in
the previous 6 months, excepting in the emergency, and the perfect obliteration
of pleural cavity to avoid next reinfection and the development of broncopleural
fistulas.
PMID- 11008414
TI - Nonlinear Markov process amplitude EEG model for nonlinear coupling interaction
of spontaneous EEG.
AB - To develop an appropriate model for representing spontaneous
electroencephalography (EEG) is an important and necessary work in the field of
neuroscience. The Markov process amplitude (MPA) EEG model has been proposed in
our previous work for representing the features of the EEG in terms of a few
parameters. However, being a linear model, the linear MPA EEG model cannot
perfectly describe the spontaneous EEG that displays nonlinear phenomena. In this
paper, the nonlinear Markov process amplitude (nonlinear MPA) EEG model that
includes nonlinear components is introduced. The consistent consideration of the
nonlinear features of the EEG investigated by N. Wiener and P. L. Nunez can be
seen from the nonlinear MPA EEG model. The similarity in the time domain and the
goodness of fitting in the frequency domain with respect to the ongoing EEG are
shown. As a result, the EEG power spectrum can be decomposed into the spontaneous
components and the nonlinearly coupled components by use of the nonlinear MPA EEG
model, which is useful for a better understanding the mechanism of the EEG
generation.
PMID- 11008415
TI - Threshold modeling of autonomic control of heart rate variability.
AB - Even in the absence of external perturbation to the human cardiovascular system,
measures of cardiac function, such as heart rate, vary with time in normal
physiology. The primary source of the variation is constant regulation by a
complex control system which modulates cardiac function through the autonomic
nervous system. Here, we present methods of characterizing the statistical
properties of the underlying processes that result in variations in ECG R-wave
event times within the framework of an integrate-and-fire model. We first present
techniques for characterizing the noise processes that result in heart rate
variability even in the absence of autonomic input. A relationship is derived
that relates the spectrum of R-R intervals to the spectrum of the underlying
noise process. We then develop a technique for the characterization of the
dynamic nature of autonomically related variability resulting from exogenous
inputs, such as respiratory-related modulation. A method is presented for the
estimation of the transfer function that relates the respiratory-related input to
the variations in R-wave event times. The result is a very direct analysis of
autonomic control of heart rate variability through noninvasive measures, which
provides a method for assessing autonomic function in normal and pathological
states.
PMID- 11008416
TI - Adaptive noise cancellation in a multimicrophone system for distortion product
otoacoustic emission acquisition.
AB - This study focuses on adaptive noise cancellation (ANC) techniques for the
acquisition of distortion product otoacoustic emissions (DPOAEs). Otoacoustic
emissions (OAEs) are very low level sounds produced by the outer hair cells of
normal cochleas, spontaneously or in response to sound stimulation as a byproduct
of a frequency and threshold sensitivity increasing mechanism. Current OAE
recording systems rely on test probe noise attenuation and synchronous ensemble
averaging for increasing signal-to-noise ratios (SNRs). The efficiency of an ANC
algorithm for noise suppression was investigated using three microphones: one
placed in the test ear, one in the nontest ear for internal noise reference; one
near the subject's head for external noise reference. The system proposed was
tested with simulations, off-line averaging and real-time implementation of the
ANC algorithm. Simulation results showed that the technique had a potential noise
reduction capability of 24 dB for complex multifrequency noise signals. Off-line
results were positive, with a mean SNR improvement of 4.9 dB. Real-time results
indicated that the use of an ANC algorithm in combination with standard averaging
methods can reduce noise levels by as much as 10 dB beyond that obtained with
standard noise reduction methods and probe attenuation alone.
PMID- 11008417
TI - An orthogonal least squares-based fuzzy filter for real-time analysis of lung
sounds.
AB - Pathological discontinuous adventitious sounds (DAS) are strongly related with
the pulmonary dysfunction. Its clinical use for the interpretation of respiratory
malfunction depends on their efficient and objective separation from vesicular
sounds (VS). In this paper, an automated approach to the isolation of DAS from
VS, based on their nonstationarity, is presented. The proposed scheme uses two
fuzzy inference systems (FISs), operating in parallel, to perform the task of
adaptive separation, resulting in the orthogonal least squares-based fuzzy filter
(OLS-FF). By applying the OLS-FF to fine/coarse crackles and squawks, selected
from three lung sound databases, the coherent structure of DAS is revealed and
they are efficiently separated from VS. The important time domain DAS features,
related to diagnostic information, are preserved and their true location and
structural morphology are automatically identified. When compared to previous
works, the OLS-FF performs quite similarly, but with significantly lower
computational load, resulting in a faster real-time clinical screening of DAS.
PMID- 11008418
TI - New aspects to event-synchronous cancellation of ECG interference: an application
of the method in diaphragmatic EMG signals.
AB - An "event-synchronous interference canceller" (ESC) for cancellation of
electrocardiographic (ECG) interference in diaphragmatic electromyographic
(EMGdi) signals is addressed in this paper. ESC pursues the concept of the "event
synchronous adaptive interference canceller" (ESAIC), which was proposed in [1]
as a specific application of the well known "adaptive noise canceller" (ANC)
paradigm, but ESC uses a simple adaptive gain control (AGC) instead of the
complex adaptive filter of the ANC. The proposed ESC method is evaluated using
both computer simulations and real EMGdi data, and its efficiency in interference
cancellation is compared to that of ESAIC. Of particular interest is the result
that the ESC can replace the ESAIC providing better performance as well as a
considerable reduction of computational costs.
PMID- 11008419
TI - Analysis of a sleep-dependent neuronal feedback loop: the slow-wave
microcontinuity of the EEG.
AB - Increasing depth of sleep corresponds to an increasing gain in the neuronal
feedback loops that generate the low-frequency (slow-wave) electroencephalogram
(EEG). We derived the maximum-likelihood estimator of the feedback gain and
applied it to quantify sleep depth. The estimator computes the fraction (0%-100%)
of the current slow wave which continues in the near-future (0.02 s later) EEG.
Therefore, this percentage was dubbed slow-wave microcontinuity (SW%). It is not
affected by anatomical parameters such as skull thickness, which can considerably
bias the commonly used slow-wave power (SWP). In our study, both of the
estimators SW% and SWP were monitored throughout two nights in 22 subjects. Each
subject took temazepam (a benzodiazepine) on one of the two nights. Both
estimators detected the effects of age, temazepam, and time of night on sleep.
Females were found to have twice the SWP of males, but no gender effect on SW%
was found. This confirms earlier reports that gender affects SWP but not sleep
depth. Subjectively assessed differences in sleep quality between the nights were
correlated to differences in SW%, not in SWP. These results demonstrate that slow
wave microcontinuity, being based on a physiological model of sleep, reflects
sleep depth more closely than SWP does.
PMID- 11008420
TI - Automatic detection of ST-T complex changes on the ECG using filtered RMS
difference series: application to ambulatory ischemia monitoring.
AB - A new detector is presented which finds changes in the repolarization phase (ST-T
complex) of the cardiac cycle. It operates by applying a detection algorithm to
the filtered root mean square (rms) series of differences between the beat
segment (ST segment or ST-T complex) and an average pattern segment. The detector
has been validated using the European ST-T database, which contains ST-T complex
episodes manually annotated by cardiologists, resulting in sensitivity/positive
predictivity of 85/86%, and 85/76%, for ST segment deviations and ST-T complex
changes, respectively. The proposed detector has a performance similar to those
which have a more complicated structure. The detector has the advantage of
finding both ST segment deviations and entire ST-T complex changes thereby
providing a wider characterization of the potential ischemic events. A post
processing stage, based on a cross-correlation analysis for the episodes in the
rms series, is presented. With this stage subclinical events with repetitive
pattern were found in around 20% of the recordings and improved the performance
to 90/85%, and 89/76%, for ST segment and ST-T complex changes, respectively.
PMID- 11008421
TI - The effect of anisotropy on the potential distribution in biological tissue and
its impact on nerve excitation simulations.
AB - We present a finite difference solution of the potential distribution associated
with electrical current stimulation in an anisotropic in-homogeneous tissue
environment and compare it to the isotropic case. The results demonstrate that
there can be significant errors associated with the assumption of isotropic
tissue properties in calculating the potential distribution along an axon in
nerve excitation simulations. These errors can have a significant impact on
predicted nerve fiber recruitment patterns when evaluating the efficacy of
specific surface or intramuscular stimulus electrode configurations. The results
of this study also suggest when a more comprehensive tissue model should be
implemented in an electrode design study. Simulation results indicate that the
isotropy assumption is worst under bipolar electrode stimulation as opposed to
monopolar stimulation and that the bipolar error increases as the distance
between electrodes decreases. In light of these results, it is concluded that in
order to avoid large errors in the calculated potential distribution along an
axon, the isotropy assumption should only be used when the transverse depth from
the electrode to the nerve is relatively small.
PMID- 11008422
TI - Pacemaker interference and low-frequency electric induction in humans by external
fields and electrodes.
AB - The possibility of interference by low-frequency external electric fields with
cardiac pacemakers is a matter of practical concern. For pragmatic reasons,
experimental investigations into such interference have used contact electrode
current sources. However, the applicability to the external electric field
problem remains unclear. The recent development of anatomically based
electromagnetic models of the human body, together with progress in computational
electromagnetics, enable the use of numerical modeling to quantify the
relationship between external field and contact electrode excitation. This paper
presents a comparison between the computed fields induced in a 3.6-mm-resolution
conductivity model of the human body by an external electric field and by several
electrode source configurations involving the feet and either the head or
shoulders. The application to cardiac pacemaker interference is also indicated.
PMID- 11008423
TI - A statistical mechanical analysis of postural sway using non-Gaussian FARIMA
stochastic models.
AB - In this paper, postural sway is modeled using a fractional autoregressive
integrated moving average (FARIMA) family of models: the center-of-pressure (COP)
motion is viewed in terms of a self-similar, anti-persistent random-walk process,
obtained by fractionally summating non-Gaussian random variables, whose
correlation structure for small time lags is shaped by a linear time-invariant
low-pass filter. The model parameters are: the strength of the stochastic
driving, e.g., the root mean square (rms) value of the time-difference COP
motion; the DC gain, damping ratio and natural frequency of the filter; the Hurst
exponent, which measures the random-walk antipersistence magnitude. In the
proposed modeling procedure, a graphical estimator for determining the Hurst
exponent is cascaded to a method for matching autoregressive (AR) models to
fractionally difference COP motion via higher order cumulants. The effect of the
presence or absence of vision on the model parameter values is discussed with
regard to data from experiments on healthy young adults.
PMID- 11008424
TI - Functional reentry's influence on intracellular calcium in the LRd membrane
equations.
AB - This paper examines relationships between transmembrane potential (Vm), [Ca2+]i
dependent membrane ionic currents, and [Ca2+]i handling by the sarcoplasmic
reticulum (SR) in a two-dimensional model of cardiac tissue. Luo-Rudy dynamic
(LRd) membrane equations were used because they include detailed formulations for
triggered SR Ca2+ release dependent on membrane Ca2+ influx (CICR) and for
spontaneous SR Ca2+ release following calsequestrin buffer overload (SCR).
Reentry's rapid rate (110-ms cycle length) elevated [Ca2+]i and limited CICR,
which in turn promoted SCR that occurred at intervals of 320-350 ms, was
preferential at sites located inside the functional center, and destabilized the
reentrant activation sequence. Although adjustment of LRd parameters for SR Ca2+
modified SCR interval and peak [Ca2+]i in voltage clamp simulations with a
command waveform representing Vm time course within the functional center, SCR
persisted. Using the same command waveform, SCR also occurred with an alternate
SR Ca2+ formulation that represented subcellular details underlying CICR. LRd
parameter adjustments to promote CICR and limit SCR in subsequent reentry
simulations failed to eliminate SCR completely, as they modulated SCR intervals
in a manner consistent with the voltage clamp simulations. Taken together, our
findings support a destabilizing influence of functional reentry on [Ca2+]i
handling. However, [Ca2+]i instabilities did not always fractionate
depolarization wavefronts during reentry. Fractionation depended, in part, upon
CICR and SCR parameters in the LRd formulation for SR Ca2+ release.
PMID- 11008425
TI - The effect of geometric and topologic differences in boundary element models on
magnetocardiographic localization accuracy.
AB - This study was performed to evaluate the changes in magnetocardiographic (MCG)
source localization results when the geometry and the topology of the volume
conductor model were altered. Boundary element volume conductor models of three
patients were first constructed. These so-called reference torso models were then
manipulated to mimic various sources of error in the measurement and analysis
procedures. Next, equivalent current dipole localizations were calculated from
simulated and measured multichannel MCG data. The localizations obtained with the
reference models were regarded as the "gold standard." The effect of each
modification was investigated by calculating three-dimensional distances from the
gold standard localizations to the locations obtained with the modified model.
The results show that the effect of the lungs and the intra-ventricular blood
masses is significant for deep source locations and, therefore, the torso model
should preferably contain internal inhomogeneities. However, superficial sources
could be localized within a few millimeters even with nonindividual, so called
standard torso models. In addition, the torso model should extend long enough in
the pelvic region, and the positions of the lungs and the ventricles inside the
model should be known in order to obtain accurate localizations.
PMID- 11008426
TI - Paired MEG data set source localization using recursively applied and projected
(RAP) MUSIC.
AB - An important class of experiments in functional brain mapping involves collecting
pairs of data corresponding to separate "Task" and "Control" conditions. The data
are then analyzed to determine what activity occurs during the Task experiment
but not in the Control. Here we describe a new method for processing paired
magnetoencephalographic (MEG) data sets using our recursively applied and
projected multiple signal classification (RAP-MUSIC) algorithm. In this method
the signal subspace of the Task data is projected against the orthogonal
complement of the Control data signal subspace to obtain a subspace which
describes spatial activity unique to the Task. A RAP-MUSIC localization search is
then performed on this projected data to localize the sources which are active in
the Task but not in the Control data. In addition to dipolar sources, effective
blocking of more complex sources, e.g., multiple synchronously activated dipoles
or synchronously activated distributed source activity, is possible since these
topographies are well-described by the Control data signal subspace. Unlike
previously published methods, the proposed method is shown to be effective in
situations where the time series associated with Control and Task activity
possess significant cross correlation. The method also allows for straightforward
determination of the estimated time series of the localized target sources. A
multiepoch MEG simulation and a phantom experiment are presented to demonstrate
the ability of this method to successfully identify sources and their time series
in the Task data.
PMID- 11008427
TI - Simultaneous optical and nuclear magnetic resonance spectroscopy for monitoring
cardiac energetics in vivo.
AB - There are a number of applications in which it is useful to simultaneously
collect data from what are traditionally separate instrumentation modalities. In
particular, in vivo physiological investigations in which data from parallel
experiments must be correlated would benefit from simultaneous data collection
through 1) elimination of subject variability, 2) elimination of treatment
variability, and 3) a reduction in the number of animal preparations required.
Here we describe the simultaneous collection of fluo-3 optical fluorescence and
31P nuclear magnetic resonance (NMR) spectra to measure intracellular calcium
levels and high-energy phosphate metabolism, respectively, in vivo. This work is
part of ongoing research into the profound anoxia tolerance exhibited by the
hearts of certain turtle species. An NMR compatible optical fluorescence
spectrometer was constructed and tested. In the 31-cm bore of a 2 T
superconducting magnet, NMR and optical spectra were collected every 10-15 min
from the in situ, in vivo hearts of anesthetized turtle subjects prior to and
during one to three hours of anoxia. It was found that while PCr stores became
significantly depleted during anoxia, beta-adenosine triphosphate (ATP) levels
remained within 20% of control values, and intracellular diastolic calcium levels
did not vary by more than 10%. The ability to make simultaneous phosphorus and
calcium measurements on a single subject is important to understanding the exact
relationship between phosphorus energy state and maintenance of calcium
homeostasis.
PMID- 11008428
TI - In vitro simultaneous measurement of refractive index and thickness of biological
tissue by the low coherence interferometry.
AB - We proposed and demonstrated in vitro simultaneous measurement of refractive
index and thickness of biological tissue. The technique is based on the low
coherence interferometry combined with precise translation stages. Refractive
indices were determined with the accuracy of less than 1% for tissue samples of a
few hundred micron thickness, including chicken tissue, human tooth and nail.
Simultaneous measurement of refractive index and thickness of multilayer tissue
are also demonstrated.
PMID- 11008429
TI - A maximum-likelihood base caller for DNA sequencing.
AB - The procedures used to sequence the human genome involve the electrophoretic
separation of mixtures of dioxyribonucleic acid (DNA) fragments tagged with
reporting groups, usually fluorescent dyes. Each fluorescent pulse which arrives
from an optical detector corresponds to a nucleotide (base) in the DNA sequence,
and the subsequent process of base detection is known as base calling. Generating
longer and more accurate sequences in the base-calling process will reduce the
high cost of DNA sequencing. This paper presents an automated base-calling
algorithm, referred to as maximum-likelihood base caller (MLB), which is based on
maximum likelihood equalization for digital communication channels. Based on 125
experimental datasets, MLB averaged up to 40% fewer errors than the widely used
ABI base caller from the Applied Biosystems Division of PE Corporation. MLB's
accuracy rivaled that of another well-known base caller, Phred, surpassing it on
datasets with high background noise.
PMID- 11008430
TI - An improved configuration for the reduction of EMG in electrode cuff recordings:
a theoretical approach.
AB - A theoretical investigation of different electroneurogram recording techniques
using electrode cuffs is presented. A new screened tripole arrangement is
proposed with a higher inherent signal to interference ratio than the true
tripole, which also allows the nulling of the residual electromyogram signal. The
reduction in interference is small because the electrode impedance is large
compared to the source resistance.
PMID- 11008431
TI - How electrode size affects the electric potential distribution in cardiac tissue.
AB - We investigate the effect of electrode size on the transmembrane potential
distribution in the heart during electrical stimulation. The bidomain model is
used to calculate the transmembrane potential in a three-dimensional slab of
cardiac tissue. Depolarization is strongest under the electrode edge. Regions of
depolarization are adjacent to regions of hyperpolarization. The average ratio of
peak depolarization to peak hyperpolarization is a function of electrode radius,
but over a broad range is close to three.
PMID- 11008432
TI - Sensitivity and versatility of an adaptive system for controlling cyclic
movements using functional neuromuscular stimulation.
AB - This study evaluated an adaptive control system (the PG/PS control system [2])
that had been designed for generating cyclic movements using functional
neuromuscular stimulation (FNS). Extensive simulations using computer-based
models indicated that a broad range of control system parameter values performed
well across a diverse population of model systems. The fact that manual tuning is
not required for each individual makes this control system particularly
attractive for implementation in FNS systems outside of research laboratories.
PMID- 11008433
TI - Selecting the corner in the L-curve approach to Tikhonov regularization.
AB - The performance of two methods for selecting the corner in the L-curve approach
to Tikhonov regularization is evaluated via computer simulation. These methods
are selecting the corner as the point of maximum curvature in the L-curve, and
selecting it as the point where the product of abcissa and ordinate is a minimum.
It is shown that both these methods resulted in significantly better
regularization parameters than that obtained with an often-used empirical
Composite REsidual and Smoothing Operator approach, particularly in conditions
where correlated geometry noise exceeds Gaussian measurement noise. It is also
shown that the regularization parameter that results with the minimum-product
method is identical to that selected with another empirical zero-crossing
approach proposed earlier.
PMID- 11008434
TI - Using evidence-based practice for managing clinical outcomes in advanced practice
nursing.
AB - Preparation of advanced practice nurses to assume leadership positions for
clinical decision making requires that traditional ways of solving clinical
problems be augmented with information from relevant, research-derived evidence.
In this article, the authors describe how one graduate program prepares advanced
practice nurses to use the best scientific evidence with clinical expertise to
influence patient outcomes. The assignments that students complete in their
program provide examples of evidence-based practice that apply quality
improvement principles and science-based nursing interventions to create best
practices.
PMID- 11008435
TI - Satisfaction with managed care.
AB - This article reports the findings of 1996, 1997, and 1998 patient satisfaction
surveys administered to managed care enrollees in Utah. More than 14,000 managed
care enrollees (both Medicaid and commercial) were selected randomly and
contacted by telephone. The 38-question survey was based on Health Plan Employer
Data and Information Set (HEDIS) and the National Committee for Quality Assurance
(NCQA) measures. Demographic differences between the commercial and Medicaid
population were identified. Medicaid enrollees were found to be higher users of
health care services. Individuals reporting the greatest health plan satisfaction
tended to be healthier. However, Medicaid enrollees reported greater overall
health plan satisfaction than commercial enrollees.
PMID- 11008436
TI - Linking nursing care interventions with client outcomes: a community-based
application of an outcomes model.
AB - This article describes a conceptual model that provides an organizing framework
for assessing client outcomes in community-based settings. The "Outcomes Model
for Community-Based Settings" (OMCBS) examines the relationships among structure,
process, and outcomes juxtaposed to the dimensions of client, provider, and
setting including sample measures for each variable. OMCBS incorporates the Omaha
System including its comprehensive list of client health problems, nursing
interventions, and an outcome rating scale assessing client knowledge, behavior,
and health status to standardize nursing care and client outcomes. The OMCBS
provides a strategy to evaluate the effectiveness of nursing interventions for
clients in a variety of milieus.
PMID- 11008437
TI - Critical care admissions criteria in community based hospitals: a pilot study
with implications for quality management.
AB - Critical care nurses are increasingly vulnerable to crises of decision-making.
Lack of enforcement or vague admission guidelines in many critical care units-
including physician coverage and time limits for newly admitted patients--might
lead to quality of care concerns. Managers struggle with staffing shortages,
decreasing resources to provide high-technology care, and in many instances the
lack of administrative support to enforce criteria for utilization of critical
care beds. This pilot study addresses quality of care concerns and other issues
that are a great source of frustration for critical care nursing staff.
PMID- 11008438
TI - Medication error reporting: a survey of nursing staff.
AB - The objective of this article is to describe findings from a medication error
(ME) survey, to estimate the extent of ME underreporting by comparison of survey
results with written incident reports (IRs), and to determine factors associated
with IR reporting of MEs. Participants were registered nurses from the 38-bed
infant unit of a pediatric hospital. Most recent ME in each of four stages of the
medication process was classified as to: timing, nature, whether the error was
prevented from the patient, patient injury, and completed IR. Surveys were
administered to nurses during mandatory skills session and were compared with IRs
for MEs for the previous 6 months. The survey response rate was 93.5 percent; 72
nurses described 177 errors, 40.3 percent observed an ME in the previous week,
62.1 percent were prevented from reaching the patient and the likelihood of
prevention was reduced in the later stages of the medication process. About 30
percent of MEs resulted in IRs. Administration errors were more likely to result
in IRs compared with ordering errors, especially when the error was not prevented
from the patient. There were 51 IRs for MEs. A multivariate logistic regression
with completed IRs as the dependent variable showed a decreased likelihood of IRs
for ordering than administration errors. IRs were more likely for wrong
medication or dose errors and IRs were less likely for errors prevented from
reaching the patient. The study found that by augmenting IR reporting of MEs and
classifying errors by stage, anonymous ME surveys can be used for monitoring and
guiding improvements to hospital medication systems.
PMID- 11008439
TI - Performance improvement through clinical research utilization: the linkage model.
AB - Performance improvement offers tremendous opportunities for research utilization
in the clinical setting. The linkage model of research utilization is
characterized by a user system that accesses a resource system, adapting research
findings to clinical practice. A performance improvement consultant can be the
link between these systems. Research application can be instrumental in improving
care delivery as demonstrated in a project concentrating on the management of
individuals experiencing a cerebrovascular accident.
PMID- 11008440
TI - Nonlinear dynamics: chaos and catastrophe theory.
AB - Nonlinear relationships are attracting much attention in nursing. Nonlinear
dynamics are used abstractly as theory and also may be applied in a concrete
sense to explain data. There is often confusion and misunderstanding about
aspects of nonlinear dynamics. This article explores two of the more well known
areas of nonlinear dynamics--chaos and catastrophe theory. A summary of each is
given, areas of commonality and distinction are explored, and guidelines for
application are identified.
PMID- 11008441
TI - Tubular contents of equine dentin: a scanning electron microscopic study.
AB - The dentinal tubules of 20 permanent equine incisors were investigated by
scanning electron microscopy. Occlusal surfaces and longitudinal fracture planes
of both etched and undecalcified teeth were examined. Three different types of
structure were observed inside the dentinal tubular lumen. Odontoblastic
processes could only be visualized in the circumpulpal parts of the tubules. The
more peripheral parts were empty or housed cylindrical structures that probably
correspond to the laminae limitantes. Collagen fibres were frequently observed in
the tubular lumina and were most numerous in the circumpulpal parts of the
tubules.
PMID- 11008442
TI - Inheritance of disc calcification in the dachshund.
AB - The occurrence of intervertebral disc calcification was investigated by
conventional spinal radiography in eight families of wirehaired dachshunds, with
each family comprising one sire, two dams and one litter from each dam. Each
offspring was examined radiographically once at 24-35 months of age. The
occurrence of disc calcification was rated according to four different scales. A
strong correlation was found in the occurrence of disc calcification between
offspring and mean parent (P < 0.001) and between offspring and dams (P < 0.005)
on an either/or scale. Statistically significant estimates of heritability of
0.60 and 0.87 were found based on the offspring-sire relationship using the total
score and three-class scale, respectively. Higher correlation estimates were
found based on the dam-offspring relationship than based on the sire-offspring
relationship, suggesting an effect of maternal environmental factors.
PMID- 11008443
TI - Cardiopulmonary side-effects and pharmacokinetics of an emulsion of propofol
(Disoprivan) in comparison to propofol solved in polysorbate 80 in goats.
AB - The aim of this study was to determine whether any pharmacokinetic or
pharmacodynamic differences exist in goats between propofol in its currently
licensed form (Disoprivan) and a new 1% solution of propofol (NSP) containing
polysorbate 80. Nine goats received, on two different occasions in a randomized
double-blinded order, 4 mg/kg propofol intravenously (i.v.; Disoprivan or NSP).
To detect differences in cardiopulmonary effects and pharmacokinetics, the
Wilcoxon signed rank test for paired data was used. In the NSP group the duration
of initial apnoea was significantly longer, and 6 and 12 min after drug
application PaO2 levels were significantly lower than in the Disoprivan group.
Mean cardiovascular parameters did not differ significantly between the groups
but in the NSP group in six goats marked changes in blood pressure occurred:
systolic arterial pressures fell to a minimum of 40-60 mmHg within the first 10
min. This was followed by a marked increase in blood pressure, with maxima
exceeding 300 mmHg. In the NSP group the half-life of propofol was significantly
longer, the clearance rate was smaller and the areas under the drug concentration
time curves were larger than in the Disoprivan group. The cardiopulmonary side
effects of NSP suggest that propofol dissolved in polysorbate 80 is not a
suitable alternative to the current formulation of propofol.
PMID- 11008444
TI - Clinical experiences of treating septic arthritis in the equine by repeated joint
lavage: a series of 39 cases.
AB - The condition of septic arthritis was treated in 12 foals with 21 affected joints
(Group I) and in 27 adult horses. The adult horses were divided into three
groups, based on aetiology of the condition: haematogenous (Group II, n = 6),
iatrogenic (Group III, n = 6), and perforating trauma (Group IV, n = 15). The
treatment consisted of an initial systemic antibiotic that anticipated the
microbial agents that were considered most likely per group, repeated through-and
through joint lavages every other day and non-steroidal anti-inflammatory drugs.
The antibiotics were adjusted to the results of bacteriological culture and
susceptibility tests. Joint lavages were continued until the white blood cell
count dropped below 15 G/l and bacteriological culture was negative, after which
a single dose of a short-acting corticosteroid was administered intra
articularly. Joint recovery rate in group I was 71%. Patient recovery rate of the
foals, however, was lower (42%). Three foals were killed for reasons other than
arthritis; one foal because of an arthritis-related problem and three foals
because of persistent arthritis. Overall joint recovery rate, equalling patient
recovery rate, in the adult horses was 81%. The expected predominance of
Streptococcus spp. in haematogenous arthritis in adult horses was not confirmed,
indicating that in these cases also, an initial antibiotic treatment with a broad
spectrum combination is preferable. It is concluded that with intensive
treatment, the prognosis of septic arthritis in the adult horse can be classified
as fair to even good. Results in the foals are not as good, but this seems to be
more due to the specific problems surrounding the equine neonate than to
unresponsiveness to the treatment.
PMID- 11008445
TI - Effect of calcium supplements to a maize-soya diet on the bioavailability of
minerals and trace elements and the accumulation of heavy metals in growing rats.
AB - Thirty-five (five groups with seven animals each) male albino rats (initial
average weight = 44 g) were fed phytate-rich diets (analysed phytic acid
concentration = 6.9 g/kg) based on maize and soy bean meal (5 g Ca, 3 g P, 1.2 g
Mg, 23 mg Zn, 10 mg Pb, 5 mg Cd/kg diet). Experimental diets were supplemented
with 0, 2, 4, 6 and 8 g calcium from CaCO3 per kg. The supplementation of
increasing amounts of calcium resulted in a dose-dependent decrease in the
apparent absorption of phosphorus. Furthermore, apparent zinc absorption and
femur zinc concentration were moderately decreased due to the calcium
supplementation. Kidney Cd concentration was significantly lower in rats that
were fed the high calcium diets in comparison with the control animals. Femur
lead concentration and hepatic delta-aminolevulinic acid dehydratase, which are
known to be sensitive parameters of lead accumulation remained unchanged by the
different dietary treatments. Magnesium absorption as well as liver and plasma
zinc concentration and activity of plasma alkaline phosphatase were also
unaffected. Although calcium supplementation may lead to a decrease in the
accumulation of certain heavy metals such as cadmium, the carry-over of lead was
not affected under the given experimental conditions. Furthermore, calcium
phytate-zinc interactions may adversely affect zinc bioavailability in growing
rats.
PMID- 11008446
TI - Stability of tetracycline in water and liquid manure.
AB - The objective of this study was to establish a suitable model for the prediction
of the environmental stability of antibiotics in water and liquid manure. The
model consists of incubation systems for solutions with installations for
stirring ventilation. It was used to examine the stability of tetracycline in
ventilated and unventilated Ringer's solution and liquid pig manure for a period
of 8 days. Tetracycline concentrations decreased significantly during the
experiment. The fastest degradation was observed in ventilated liquid manure. The
test might be used as a screening test for the determination of the degradation
half-life of antibiotics in the first phase of an environmental safety study
according to directive 92/18/EEC.
PMID- 11008447
TI - [Lawyers and journalists].
PMID- 11008448
TI - [Ketolides].
PMID- 11008449
TI - [Arthrosis and arthritis].
PMID- 11008450
TI - [Common colds and their complications].
PMID- 11008451
TI - [Nose drops. Applications, indications, alternatives].
PMID- 11008452
TI - Pepper spray just won't go away.
PMID- 11008453
TI - Medical malpractice: 'fixing' is not so simple.
PMID- 11008454
TI - Public health, safety, and financial problems posed by domestic violence (DV)
PMID- 11008455
TI - Physician assistants. A young profession celebrates the 35th anniversary of its
birth in North Carolina.
PMID- 11008456
TI - Brainwashing and battering fatigue. Psychological abuse in domestic violence.
AB - Intimate partner violence occurs often in the United States; it involves an
interrelated combination of physical, sexual, and psychological abuse, usually
directed against women. The psychological aspect deserves special attention
because victims who lose their independence, self-esteem, and dignity tend to
remain in abusive situations. The abuse is perpetrated by a domestic partner to
maintain power and control in the relationship. To assert control, the abuser
uses "brainwashing tactics" similar to those used on prisoners of war, hostages,
or members of a cult. Common features of brainwashing include isolation,
humiliation, accusation, and unpredictable attacks. The abusive environment
produces real and anticipated fear, which contributes to the battered woman's
belief that her situation is hopeless and that she must depend on her abuser. She
develops coping strategies to deal with her oppressive environment, but
eventually exhibits symptoms of "battering fatigue," similar to the battle
fatigue of soldiers in combat who, like battered women, live in fear of being
killed or severely injured. Recognizing the state of mind of these women can help
us understand why it is difficult for them to flee their traumatic environment
and why they may resort to suicide or homicide. For healthcare providers to
screen and treat their patients adequately, it is imperative that they appreciate
the complex and devastating psychological aspects of domestic violence.
PMID- 11008457
TI - The doctor as witness. How good medical records can help victims of domestic
violence, minimize time in court, and maximize effective testimony.
PMID- 11008458
TI - Domestic violence and children. A review.
PMID- 11008459
TI - Emergency medical services personnel and domestic violence.
PMID- 11008460
TI - Lethal domestic violence in eastern North Carolina.
AB - Strategies for preventing domestic violence can be tailored to a particular
geographic or socioeconomic area if the patterns of domestic violence in the area
are known. National statistics, although widely available, may not be applicable
to a specific region. We reviewed homicide deaths in Eastern North Carolina
between 1978 and 1999 to identify patterns in this rural area. Approximately 20%
of the homicide deaths in eastern North Carolina are caused by intimate partners.
Women accounted for 53% of the victims in 1976, similar to national figures but
not rising to 72% as seen nationally in 1998. Latinos are an increasing presence
in the area, but had only one recorded episode of lethal violence against an
intimate partner. Gunshots accounted for most of the deaths (59% in men, 72% in
women). Knowledge of such patterns can assist in selecting prevention strategies
for this particular area. Over the last 25 years increasing attention has been
devoted to domestic violence (DV), initially defined as abuse committed against a
spouse, former spouse, fiancee, boy- or girlfriend, or cohabitant. As time has
passed, the definition has been broadened to include other family members-
elders, children, and siblings. The Centers for Disease Control and Prevention
(CDC) now uses the term "intimate partner violence" for intentional emotional or
physical abuse inflicted by a spouse, ex-spouse, a present or former boy- or
girlfriend, or date. For the purposes of this paper, we consider DV
interchangeable with intimate partner violence. There has been a national concern
that abusive events are under-reported. The National Crime Victimization Survey,
an anonymous household survey, indicated nearly 1 million incidents of non-lethal
intimate partner violence per year between 1992 and 1996. The number decreased
from 1.1 million in 1993 to 840,000 in 1996. Attempts to validate such data for a
given geographic area often require subjects to violate anonymity--this may
account for lower reports of violence. A recent national report from the Justice
Department found a decline in both lethal and non-lethal DV. The number of men
murdered by wives or girlfriends "plunged 60% from 1976 through 1998". FBI data
on homicides showed that "intimate partners committed fewer murders each year
during 1996, 1997, and 1998 than in any other year since 1976". Nationally,
intimate partners caused 3000 deaths in 1976, 1590 (53%) in women; in 1998, they
caused 1830 deaths, 1320 (73%) in women. But fatal cases of DV are only the tip
of the iceberg, and may pertain only to a particular geographic area. We
undertook the present study to assess the prevalence of lethal domestic violence
in the 29 counties of eastern North Carolina (ENC) that make up the catchment
area for the University Health Systems of Eastern Carolina (UHSEC). UHSEC
includes the Brody School of Medicine at East Carolina University (BSM-ECU;
previously known as East Carolina University-SOM) and Pitt County Memorial
Hospital.
PMID- 11008461
TI - Elder mistreatment. A guide for medical professionals.
PMID- 11008462
TI - [Photodynamic therapy in pneumology].
PMID- 11008463
TI - [Effect of ambroxol on surfactant secretion and synthesis in isolated type II
alveolar cells].
AB - The effect of ambroxol is attributed in part to an effect on surfactant synthesis
and secretion. Evidence supporting this hypothesis is largely indirect; a direct
effect of ambroxol on surfactant synthesis and secretion remains to be
demonstrated. In this study a direct effect of ambroxol was evaluated using
isolated alveolar type II cells. Secretion of labelled phosphatidylcholine was
measured following the addition of increasing concentrations (10(-8) M to 10(-4)
M) of ambroxol to the culture medium for increasing time intervals. There was no
significant increase in surfactant secretion with increased ambroxol
concentration or prolonged exposure time. Uptake of 3H-choline and synthesis into
3H-phosphatidylcholine was analyzed as an indicator of surfactant synthesis.
Again, increasing concentrations of ambroxol (10(-7) M to 10(-5) M) were followed
for 1, 2, 4, 8 and 24 h. There was no significant effect on synthesis at any time
point. Concentrations higher than those mentioned here resulted in LDH release
from cultured cells. Ambroxol which also has anti-oxidative and anti-inflammatory
effects does not exhibit direct stimulatory effects on surfactant synthesis and
secretion in isolated (rat) alveolar type II cells as has been demonstrated e.g.
for beta 2-adrenergic stimulation. A specific pharmacologic way to stimulate the
surfactant system remains to be developed.
PMID- 11008464
TI - [Indications for corticosteroid therapy and sarcoidosis and the assessment of the
results].
PMID- 11008465
TI - [Protective vaccination against pneumococci].
PMID- 11008466
TI - [Methods for the costing process in the field of economic evaluation of a
rehabilitation program for patients with chronic obstructive lung diseases].
AB - Studies in health economics especially economic evaluations of health care
technologies and programmes are getting more and more important. However, in
Germany there are no established, validated and commonly used instruments for the
costing process. For the economic evaluation of a rehabilitation programme for
patients with chronic lung diseases such as asthma and chronic bronchitis we
developed methods for identification, measurement and validation of resource use
during the inpatient rehabilitation programme and during the outpatient follow-up
period. These methods are based on methodological considerations as well as on
practical experience from conducting a pilot study. With regard to the inpatient
setting all relevant diagnostic and therapeutic resource uses could be measured
basing on routine clinical documentation and validated by using the cost
accounting of the clinic. For measuring the use of resources during the follow-up
period in an outpatient setting no reliable administrative data are accessible.
Hence, we compared a standardised retrospective patient questionnaire used in a
20-minute interview (n = 50) and a cost diary for the continuing documentation by
the patient over a period of 4 weeks (n = 50). Both tools were useful for
measuring all relevant resource uses in sufficient detail, but because of higher
participation rates and lower dropouts the structured interview appears to be
more suitable. Average total costs per month were 1591 DM (interview),
respectively 1867 DM (cost diary). Besides productivity loss, costs for
medication and GP visits caused the relatively highest resource uses. Practicable
instruments were developed for the costing process as part of an economic
evaluation in a German rehabilitation setting for pulmonary diseases. After
individual modification, these could also be used for different indications and
in other institutional settings.
PMID- 11008467
TI - [Individualized, modular structured patient behavioral training in obstructive
airway diseases during inpatient rehabilitation].
PMID- 11008468
TI - [COPD--a diagnostic and therapeutic challenge. Congress report on the workshop of
Boehringer Ingelheim Pharma KG on March 3 20000 in Hamburg in the framework of
the 20th congress of the German Society of Pneumology].
PMID- 11008469
TI - [Long-term oxygen therapy--from whom and how? Results of expert discussion in the
framework of Pneumology Workships "COPD--an inventory at the beginning of the
21st century by Boehringer Ingelheim Pharma KG, Ingelheim on January 21 2000 in
Seefeld, Tyrol].
PMID- 11008470
TI - [An invasive bronchoscopic strategy in the treatment of patients with suspected
ventilator-associated pneumonia is not a superior clinical strategy].
PMID- 11008471
TI - lGradation of sideropneumoconiosis.
AB - Pathological-anatomical analyses of biopsy and autopsy samples of 43 men with
anamnestically established occupational exposure to welding fumes showed in 38
specimens (88%) characteristic alterations of varying degrees of sidero
pneumokonioses. Based on recurrent histological findings of increase and
activation of iron storing macrophages (siderophages) and varying degrees of
fibrosis, sidero pneumokonioses are classified into three grades.
Intraindividually and also toporegionally different degrees may well be present.
Based on morphological criteria of the three grades, seven samples were
classified as grade I, 21 specimens as grade II, and 10 samples as grade III. The
results show that exposure to welding fumes may well cause pulmonary alterations
reaching an impairment level, depending on length, extent and special
circumstances of the respective exposure. In cases of so-called welders lungs, an
obliging statement in an expert's opinion on the degree of functional impairment,
however, can only be given when histological findings, detailed information on
the occupational history and clinical functional parameters are combined.
PMID- 11008472
TI - [Role of surgical procedures in the diagnosis and therapy of tuberculosis].
AB - Over the last decades the annual number of surgical intervention for treatment of
pulmonary tuberculosis has steadily declined. Despite effective antituberculotic
medication, there are still indications for thoracic surgery. The aim of the
present study was to give an account of the diagnostic and therapeutic role of
surgery of pulmonary tuberculosis. Therefore we analysed all operated patients
with pulmonary tuberculosis between 1988 and 1999. In 2% of all patients with
pulmonary tuberculosis surgical intervention was performed (n = 35). Their main
indication was resection for suspected carcinoma, multi-drug resistance or non
compliance to the medical treatment, decortication because of cavern rupture or
empyema, hemoptoe and destroyed lung. A additional indication for surgery was
pulmonary aspergilloma caused by superinfection of postspecific cavities.
Postoperative complications like bleeding (> 1000 ml) or broncho-pleural fistula
occurred in 37%, none of the patients died. Surgery is still a valid option fur
the treatment of pulmonary tuberculosis. Before surgical intervention, a long
term antituberculotic chemotherapy is essential. Patients have to be selected
individually because of an increased morbidity. In 10% of all operated patients
(n = 1132) with preoperative unidentifiable pulmonary mass the infiltrate was
specific aetiology.
PMID- 11008473
TI - [The state of tuberculosis in Germany 1998].
PMID- 11008474
TI - [Aspects of tuberculosis].
PMID- 11008475
TI - [nCPAP therapy does not affect respiratory mechanics of patients with sleep
related respiratory disturbances].
AB - We investigated in patients with sleep disordered breathing the influence of long
term nCPAP-therapy on airway mechanics and capillary blood gases. 109 patients
(19 women, 90 men, age [mean +/- standard deviation] 59 +/- 10 years, apnea
hypopnea-index 34 +/- 24/h) were treated for 27 +/- 33 months, with a mean
pressure of 7.7 +/- 2 mbar, mean usage 5.6 +/- 1.9 h/night. Vital capacity, FEV1,
thoracic gas volume and capillary blood gases did not change during therapy,
irrespective of the smoking history. However, in a subgroup of 6 patients who
were hypoxemic before therapy, there was a significant increase of PaO2 from 63
+/- 4 to 70 +/- 6 mm Hg (p < 0.01). Neither the height of the pressure nor the
duration of therapy did influence the course of lung function data.
PMID- 11008476
TI - [The driving simulation test "carsim" for assessing vigilance. Effect of driving
practice and other factors in health subjects and in patients with sleep apnea
syndrome].
AB - Among other factors, obstructive sleep apnoea (OSAS) patients suffer from
impaired continuous attention. For registration and objectification as well as
observation of the course of therapy, driving simulation programmes are
particularly suitable. "Carsim", a driving simulation newly developed by us,
simulates a bendy road via a screen where a vehicle is supposed to be kept on the
right lane by operating a steering wheel. Apart from examination of quality
criteria (objectivity, reliability, validity) and establishment of standard
values, the influence of significant variables (age, gender, school education,
profession, duration of disorder, AHI, BMI, visual and motor functionability,
driving license, driving experience, Epworth score, accident frequency) on
patients and healthy controls requires to be evaluated. For this purpose, 100
healthy controls, 200 OSAS patients and 30 patients under nCPAP were analysed. In
healthy persons and patients under nCPAP, driving experience had no impact on the
driving simulation results. OSAS patients with no driving license and no driving
experience achieved lower marks for tracking than patients with driving license
or a lot of driving experience (no driving license: x = 8058 +/- 10,878 track
deviations; with driving licence: x = 2111 +/- 6564 track deviations; p < .001).
According to our findings, untreated OSAS severely interferes with patients'
attention capacity as well as their coping strategies.
PMID- 11008477
TI - [From physiopathology to new developments in pharmacotherapy of bronchial asthma-
a look into the future].
PMID- 11008478
TI - [Isolated tumor cells in bone marrow predicts reduced survival in lymph node
negative non-small-cell lung cancer].
AB - BACKGROUND: It became recently evident that isolated tumor cells undetectable by
conventional tumor staging are frequently present in bone marrow of patients with
apparently localized non-small cell lung cancer (NSCLC). The clinical relevance
of this minimal hematogenous tumor cell dissemination is under vigorous debate.
METHODS: For tumor cell detection in the bone marrow we used monoclonal antibody
CK2 against the epithelial intermediate filament protein cytokeratin 18. The
influence of a positive bone marrow finding on clinical outcome was studied in
139 patients with NSCLC postoperatively staged as pT1-4, pN0-2, M0, R0 after a
median follow up of 66 months (48-74). FINDINGS: Cytokeratin-18-positive cells in
bone marrow were demonstrated in 83 (59.7%) patients at the time of primary
surgery and in 6 of 12 representative patients analyzed twice 3-18 months after
surgery. In patients without histopathological lymph node metastases (pN0; n =
66) the occurrence of > or = 2 tumor cells in bone marrow at primary surgery was
a strong and independent predictor for overall survival (p = 0.007) in univariate
analysis. The multivariate analysis showed a 2.8 times increased risk for shorter
survival in patients with disseminated tumor cells versus patients without such
cells. Four of the six patients with a positive CK status after surgery developed
a tumor recurrence 11-44 months after the operation, while in none of the
patients with a negative bone marrow at all times intervals showed a tumor
relapse. CONCLUSIONS: Minimal residual bone marrow involvement is an independent
prognostic factor for overall survival in patients with node-negative NSCLC,
which may help to identify patients in need of an adjuvant systemic therapy. The
postoperative persistence or re-appearance of tumor cells in bone marrow
indicates that these are not only shredded cells but rather represent true
micrometastasis.
PMID- 11008479
TI - [Recommendations on the diagnosis of bronchial carcinoma. German Pneumology
Society].
PMID- 11008480
TI - [Effects of significantly increased perinatal risks on developmental status in
adolescence].
AB - In a 13-years-catamnesis a sample of 50 children with severe perinatal risks was
assessed with regard to their physical, cognitive and behavioral development;
selective drop-outs were analysed. In accordance with the results of other
prospective studies there are deficits in visual-motor functioning, higher rates
of somatic complaints, social withdrawal and attention deficits; a large number
of these children attend special schools. The study presents predicative
relations between risk factors of birth-time and the developmental status at
youth. In comparison with typical single risks (e.g. gestational age or
respiratory distress syndrome) a complex index for the perinatal risk, the so
called birth-optimality offers no substantial advantage. A significant influence
of social factors is shown for school achievement. Children of fathers with
higher educational level are attending schools of a higher grade. The combination
of biological and social factors improves the reliability of developmental
prognosis; the Mental Developmental Index of the Bayley Scales of Infant
Development provides additional prognostic accuracy. For compensating
developmental disadvantages especially parents with lower educational level
should be informed about beneficial care. Even children of these families, who
scored low in early cognitive assessments should receive early intervention or
therapeutic support.
PMID- 11008481
TI - [Differences in linguistic representation of 10- to 12-year-old boys of divorced
and not divorced parents].
AB - Twenty-eight 10- to 14 years old boys from divorced families (separation of the
parents was two years before the investigation) were compared with 26 10- to 14
years old boys from two-parent families on the basis of interviews about
attachment related themes and daily situations, and by means of the California
Child Q-Sort (CCQ). The interviews were analyzed with regard to coherence of
language, emotional problems, reflectivity, supportive representation of their
parents, verbal and nonverbal emotional openness and social network, as well as
for personality variables. The boys of the divorced group did barely talk about
relations, had problems in coping with emotional stress, and were less reflective
about themselves and others. They felt insufficiently supported by their parents
and did not show their emotions openly. They talked about themselves as dependent
from their social environment and as less adaptive to new situations. These
indications suggest an insecure attachment representation predominantly as a
result of the parents' behavior leading to divorce (Table 1). The results show
that separations and family disruptions, as a group effect, strongly affect pre
adolescent boys' state of mind. A minority of boys from the parental divorce
group, however, show secure mental representations, comparable to a majority in
the control group. Tables 2-5 show, independent of parental divorce, the major
differences between boys with secure and boys with insecure mental
representations.
PMID- 11008482
TI - [The General Depression Scale in diagnosis of adolescents].
AB - A German version of the Center for Epidemiological Studies Depression Scale (CES
D) was used in the Zurich Epidemiological Study of Child and Adolescent
Psychopathology (ZESCAP). Psychometric analyses revealed clear evidence of a
central factor of depression as reflected by the CES-D. Due to good reliability,
a total score of the CES-D should be used in clinical diagnostics. The first
cross-sectional wave of assessment within ZESCAP found that gender, nationality
(indigenous vs. migrants) and residence (urban vs. rural) are important
determinants of the total score. The article provides norms for adolescents. The
study of the validity of the CES-D warrants further research.
PMID- 11008483
TI - [As index patient into therapeutic alternatives?--Children in systemic family
therapy and counseling].
AB - Since systemic therapy and counseling approaches have become established in child
guidance, and children and adolescent psychiatry the understanding for children
in the therapeutic context has also changed. They are part of the family system
who, with their symptoms, point to restricting reality constructions and
interaction patterns which create suffering (index patients). They are often
treated correspondingly in the family setting. On this background this article
investigates the special situation of children in the practice of systemic family
therapy. The few results from studies from practice research dealing with this
subject are compared with system-theoretical basic assumptions. The results
indicate that the children are only insufficiently integrated into the therapy
sessions and are excluded partly. They often experience the family discussions as
being adult-oriented and feel that their needs and views are considered only
slightly. Possible causes for this may be expecting too much emotionally and/or
cognitively especially from younger children with family-oriented methods (such
as circular questioning) as well as deficits in the training of family
therapists. The closing thoughts on the therapeutic implications from the
presented results include suggestions on methodical approaches more suitable for
children and a reflected therapeutic attitude (transparency, participation,
respect) towards children.
PMID- 11008484
TI - Cyclic nucleotide phosphodiesterases: relating structure and function.
AB - Cyclic nucleotide phosphodiesterases (PDEs) comprise a superfamily of
metallophosphohydrolases that specifically cleave the 3',5'-cyclic phosphate
moiety of cAMP and/or cGMP to produce the corresponding 5'-nucleotide. PDEs are
critical determinants for modulation of cellular levels of cAMP and/or cGMP by
many stimuli. Eleven families of PDEs with varying selectivities for cAMP or cGMP
have been identified in mammalian tissues. Within these families, multiple
isoforms are expressed either as products of different genes or as products of
the same gene through alternative splicing. Regulation of PDEs is important for
controlling myriad physiological functions, including the visual response, smooth
muscle relaxation, platelet aggregation, fluid homeostasis, immune responses, and
cardiac contractility. PDEs are critically involved in feedback control of
cellular cAMP and cGMP levels. Activities of the various PDEs are highly
regulated by a panoply of processes, including phosphorylation events,
interaction with small molecules such as cGMP or phosphatidic acid, subcellular
localization, and association with specific protein partners. The PDE superfamily
continues to be a major target for pharmacological intervention in a number of
medically important maladies.
PMID- 11008485
TI - Thyroid hormone regulation of apoptotic tissue remodeling: implications from
molecular analysis of amphibian metamorphosis.
AB - Organogenesis and tissue remodeling are critical processes during postembryonic
animal development. Anuran metamorphosis has for nearly a century served as an
excellent model to study these processes in vertebrates. Frogs not only have
essentially the same organs with the same functions as higher vertebrates such as
humans, but also employ similar organogenic processes involving highly conserved
genes. Development of frog organs takes place during metamorphosis, which is free
of any maternal influences but absolutely dependent on the presence of thyroid
hormone. Furthermore, this process can be easily manipulated both in intact
tadpoles and in organ cultures by controlling the availability of thyroid
hormone. These interesting properties have led to extensive morphological,
cellular, and biochemical studies on amphibian metamorphosis. More recently, the
cloning of thyroid hormone receptors and the demonstration that they are
transcription factors have encouraged enormous interest in the molecular pathways
controlling tissue remodeling induced by thyroid hormone during metamorphosis.
This article summarizes some of the recent studies on the mechanisms of gene
regulation by thyroid hormone receptors and isolation and functional
characterization of genes induced by thyroid hormone during Xenopus
metamorphosis. Particular focus is placed on the remodeling of the animal
intestine, which involves both apoptosis (programmed cell death) of larval cells
and de novo development of adult tissues, and the roles of thyroid hormone
induced genes that encode matrix metalloproteinases during this process.
PMID- 11008486
TI - Role of S6 phosphorylation and S6 kinase in cell growth.
AB - This article reviews our current knowledge of the role of ribosomal protein S6
phosphorylation and the S6 kinase (S6K) signaling pathway in the regulation of
cell growth and proliferation. Although 40S ribosomal protein S6 phosphorylation
was first described 25 years ago, it only recently has been implicated in the
translational up-regulation of mRNAs coding for the components of protein
synthetic apparatus. These mRNAs contain an oligopyrimidine tract at their 5'
transcriptional start site, termed a 5'TOP, which has been shown to be essential
for their regulation at the translational level. In parallel, a great deal of
information has accumulated concerning the identification of the signaling
pathway and the regulatory phosphorylation sites involved in controlling S6K
activation. Despite this knowledge we are only beginning to identify the direct
upstream elements involved in growth factor-induced kinase activation. Use of the
immunosupressant rapamycin, a bacterial macrolide, in conjunction with dominant
interfering and activated forms of S6K1 has helped to establish the role of this
signaling cascade in the regulation of growth and proliferation. In addition,
current studies employing the mouse as well as Drosophila melanogaster have
provided new insights into physiological function of S6K in the animal. Deletion
of the S6K1 gene in mouse cells led to an animal of reduced size and the
identification of the S6K1 homolog, S6K2, whereas loss of dS6K function in
Drosophila demonstrated its paramount importance in development and growth
control.
PMID- 11008487
TI - Molecular characterization of monoamine oxidases A and B.
AB - Monoamine oxidase A and B (MAO A and B) are the major neurotransmitter-degrading
enzymes in the central nervous system and in peripheral tissues. MAO A and B
cDNAs from human, rat, and bovine species have been cloned and their deduced
amino acid sequences compared. Comparison of A and B forms of the enzyme shows
approximately 70% sequence identity, whereas comparison of the A or B forms
across species reveals a higher sequence identity of 87%. Within these sequences,
several functional regions have been identified that contain crucial amino acid
residues participating in flavin adenine dinucleotide (FAD) or substrate binding.
These include a dinucleotide-binding site, a second FAD-binding site, a
fingerprint site, the FAD covalent-binding site, an active site, and the membrane
anchoring site. The specific residues that play a role in FAD or substrate
binding were identified by comparing sequences in wild-type and variants of MAO
with those in soluble flavoproteins of known structures. The genes that encode
MAO A and B are closely aligned on the X chromosome (Xp11.23), and have identical
exon-intron organization. Immunocytochemical localization studies of MAO A and B
in primate brain showed distribution in distinct neurons with diverse
physiological functions. A defective MAO A gene has been reported to associate
with abnormal aggressive behavior. A deleterious role played by MAO B is the
activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a
proneurotoxin that can cause a parkinsonian syndrome in mammals. Deprenyl, an
inhibitor of MAO B, has been used for the treatment of early-stage Parkinson's
disease and provides protection of neurons from age-related decay.
PMID- 11008488
TI - Squalene synthase: structure and regulation.
AB - Squalene synthase (SQS) catalyzes the first reaction of the branch of the
isoprenoid metabolic pathway committed specifically to sterol biosynthesis.
Regulation of SQS is thought to direct proximal intermediates in the pathway into
either sterol or nonsterol branches in response to changing cellular
requirements. The importance of SQS in cholesterol metabolism has stimulated
research on the mechanism, structure, and regulation of the enzyme. SQS produces
squalene, a C30 isoprenoid, in a two-step reaction in which two molecules of
farnesyl diphosphate are condensed head to head. Site-directed mutagenesis of rat
SQS has identified conserved Tyr, Phe, and Asp residues that are essential for
function. The aromatic rings of Tyr and Phe are postulated to stabilize
carbocation intermediates of the first and second half-reactions, respectively;
the acidic Asp residues may be required for substrate binding. SQS activity,
protein level, and gene transcription are strictly and coordinately regulated by
cholesterol status, decreasing with cholesterol surfeit and increasing with
cholesterol deficit. The human SQS (hSQS) gene has an unusually complex promoter
with multiple binding sites for the sterol regulatory element binding proteins
SREBP-1a and SREBP-2, and for accessory transcription factors known to be
involved in the control of other sterol-responsive genes. SREBP-1a and SREBP-2
require different subsets of hSQS regulatory DNA elements to achieve maximal
promoter activation. Current research is directed at elucidating the precise
contribution made by individual SREBPs and accessory transcription factors to
hSQS transcriptional control.
PMID- 11008489
TI - Yeast chromatin structure and regulation of GAL gene expression.
AB - Yeast genomic DNA is covered by nucleosome cores spaced by short, discrete length
linkers. The short linkers, reinforced by novel histone properties, create a
number of unique and dynamic nucleosome structural features in vivo: permanent
unpeeling of DNA from the ends of the core, an inability to bind even full 147 bp
core DNA lengths, and facility to undergo a conformational transition that
resembles the changes found in active chromatin. These features probably explain
how yeast can maintain most of its genome in a transcribable state and avoid
large-scale packaging away of inactive genes. The GAL genes provide a closely
regulated system in which to study gene-specific chromatin structure. GAL
structural genes are inactive without galactose but are highly transcribed in its
presence; the expression patterns of the regulatory genes can account for many of
the features of GAL structural gene control. In the inactive state, GAL genes
demonstrate a characteristic promoter chromosomal organization; the major
upstream activation sequence (UASG) elements lie in open, hypersensitive regions,
whereas the TATA and transcription start sites are in nucleosomes. This
organization helps implement gene regulation in this state and may benefit the
organism. Induction of GAL expression triggers Gal4p-dependent upstream
nucleosome disruption. Disruption is transient and can readily be reversed by a
Gal80p-dependent nucleosome deposition process. Both are sensitive to the
metabolic state of the cell. Induction triggers different kinds of nucleosome
changes on the coding sequences, perhaps reflecting the differing roles of
nucleosomes on coding versus promoter regions. GAL gene activation is a complex
process involving multiple Gal4p activities, numerous positive and negative
cofactors, and the histone tails. DNA bending and chromosomal architecture of the
promoter regions may also play a role in GAL regulation. Regulator-mediated
competition between nucleosomes and the TATA binding protein complex for the TATA
region is probably a central aspect of GAL regulation and a focal point for the
numerous factors and processes that contribute to it.
PMID- 11008490
TI - A coordinated interplay: proteins with multiple functions in DNA replication, DNA
repair, cell cycle/checkpoint control, and transcription.
AB - In eukaryotic cells, DNA transactions such as replication, repair, and
transcription require a large set of proteins. In all of these events, complexes
of more than 30 polypetides appear to function in highly organized and
structurally well-defined machines. We have learned in the past few years that
the three essential macromolecular events, replication, repair, and
transcription, have common functional entities and are coordinated by complex
regulatory mechanisms. This can be documented for replication and repair, for
replication and checkpoint control, and for replication and cell cycle control,
as well as for replication and transcription. In this review we cover the three
different protein classes: DNA polymerases, DNA polymerase accessory proteins,
and selected transcription factors. The "common enzyme-different pathway
strategy" is fascinating from several points of view: first, it might guarantee
that these events are coordinated; second, it can be viewed from an evolutionary
angle; and third, this strategy might provide cells with backup mechanisms for
essential physiological tasks.
PMID- 11008491
TI - Signal transduction pathways and the modification of chromatin structure.
AB - Mechanical and chemical signaling pathways are involved in transmitting
information from the exterior of a cell to its chromatin. The mechanical
signaling pathway consists of a tissue matrix system that links together the
three-dimensional skeletal networks, the extracellular matrix, cytoskeleton, and
karyoskeleton. The tissue matrix system governs cell and nuclear shape and forms
a structural and functional connection between the cell periphery and chromatin.
Further, this mechanical signaling pathway has a role in controlling cell cycle
progression and gene expression. Chemical signaling pathways such as the
Ras/mitogen-activated protein kinase (MAPK) pathway can stimulate the activity of
kinases that modify transcription factors, nonhistone chromosomal proteins, and
histones. Activation of the Ras/MAPK pathway results in the alteration of
chromatin structure and gene expression. The tissue matrix and chemical signaling
pathways are not independent and one signaling pathway can affect the other. In
this chapter, we will review chromatin organization, histone variants and
modifications, and the impact that signaling pathways have on chromatin structure
and function.
PMID- 11008492
TI - RGS proteins: lessons from the RGS9 subfamily.
AB - RGS proteins enhance the time resolution of G protein signaling cascades by
accelerating GTP hydrolysis of G alpha subunits of heterotrimeric G proteins.
RGS9-1, a photoreceptor-specific RGS protein, is the first vertebrate member of
this sizeable family whose physiological function in a well-defined G protein
pathway has been identified. It is essential for normal subsecond recovery
kinetics of the light responses in retinal photoreceptors. Understanding this
role allows RGS9-1 to serve as a useful model for understanding how specificity
and regulation of RGS function are achieved. In addition to the catalytic RGS
domain, shared among all members of this family, RGS9-1 contains several other
domains, which are also found in a closely related subset of RGS proteins, the
RGS9 subfamily. One of these domains, the G gamma-like (GGL) domain, has been
identified as the attachment site for G beta 5 proteins, which act as obligate
subunits for this subfamily. Results from RGS9-1 and other subfamily members
suggest that specificity is achieved by cell type-specific transcription, RNA
processing, and G beta 5-dependent protein stabilization. In addition, membrane
localization via specific targeting domains likely plays an important role.
PMID- 11008494
TI - [Will refractive surgery replace glasses?].
PMID- 11008493
TI - Regulation of mammalian cell membrane biosynthesis.
AB - This review explores current information on the interrelationship between
phospholipid biochemistry and cell biology. Phosphatidylcholine is the most
abundant phospholipid and it biosynthesis has been studied extensively. The
choline cytidylyltransferase regulates phosphatidylcholine production, and recent
advances in our understanding of the mechanisms that govern cytidylyltransferase
include the discovery of multiple isoforms and a more complete understanding of
the lipid regulation of enzyme activity. Similarities between phosphatidylcholine
formation and the phosphatidylethanolamine and phosphatidylinositol biosynthetic
pathways are discussed, together with current insight into control mechanisms.
Membrane phospholipid doubling during cell cycle progression is a function of
periodic biosynthesis and degradation. Membrane homeostasis is maintained by a
phospholipase A-mediated degradation of excess phospholipid, whereas insufficient
phosphatidylcholine triggers apoptosis in cells.
PMID- 11008495
TI - [Tuberculosis eradication: realist perspective or utopia?].
PMID- 11008496
TI - [Epidemiology and physiopathology of chronic venous leg diseases].
AB - Chronic venous disorders of the lower limbs include a wide range of clinical
manifestations involving more than one half of the population in the industrial
countries. Varicose veins have a multifactorial origin, linked to ageing,
environment (life habits, pregnancies...) and heredity. Their development is
related to an increased distensibility of the venous wall and to haemodynamic
dysfunction secondary to valvular incompetence. Cutaneous trophic changes and leg
ulcers are the final result of severe primary varicose disease or post-thrombotic
disease. Elder people are mostly concerned. Skin disease results from ambulatory
venous hyperpressure due to several types of reflux involving superficial, deep
and perforator veins. Its development is linked to a cutaneous microangiopathy,
the central element of which is a decreased capillary density. Venous symptoms
are quite widespread and women are more concerned than men; they are also of a
multifactorial origin, varicose veins being only one of the causative factors.
Their pathogenesis remains unclear, involving venous stasis and probably a
functional insufficiency of the lymphatic system.
PMID- 11008498
TI - [Primary varices of the legs].
AB - Varicose veins are a very common reason for medical referral. Diagnosis is made
on clinical examination. The disease is generally benign, but can be complicated
by cutaneous ulcers. Duplex ultrasound give informations on the superficial, deep
and perforating venous systems. Treatment is not straightforward. Recurrences are
common after surgery and sclerotherapy. Medical treatment consists in compression
hosiery and symptomatic drugs.
PMID- 11008497
TI - [Heavy and swollen legs].
AB - Painful sensation of heavy or swollen legs are non-specific symptoms frequently
associated with chronic venous insufficiency. Clinical evaluation is the first
step in defining the cause of the complaint and offering adequate treatment. When
a heavy or swollen leg is associated with oedema, venous insufficiency, lymphatic
or systemic disease must be considered. If symptoms occur during walking a
vascular or nervous disease must be suspected. Associated erythema suggests
infection (erysipelas). If clinical data are the cornerstone of diagnosis,
difficulty may arise from the high frequency of superficial venous insufficiency
and the readiness of linking too quickly any non specific complaint to this
particular venous disease.
PMID- 11008499
TI - [Drugs for veno-lymphatic insufficiency].
AB - Treatment of venous and lymphatic insufficiency of the lower limbs is based on 3
components: elastic support, venotonic drugs and radical treatments (surgery or
sclerotherapy) of insufficient veins. Venotonic drugs have specific indications
limited to functional impairment: heavy feeling in the legs, pain and impatience
in the evening. There are different categories of venolymphatic drugs. Flavonoids
have various pharmacological actions, most notably an increase in venous tone,
reduction of capillary permeability and increase of capillary resistance. Choice
of a venotonic drug is funded on knowledge of pharmacodynamics and
pharmacokinetics of the molecule, critical evaluation of clinical studies,
physician's personal experience and drug cost. Venotonic drugs are useful when
venous insufficiency leads to functional manifestations. They are especially the
treatment of heavy leg syndromes during warm seasons when elastic support is
uncomfortable.
PMID- 11008500
TI - [Manual lymphatic drainage].
AB - Manual physiotherapy of lymphoedema is the best treatment for chronic venous and
lymphatic stasis of the lower limbs. It consists in handlings of the limb for the
appeal and the resorption of the lymph but it cannot be used alone. It must be
associated with other techniques: defibrosing, skin care, compressive bandages,
muscular exercise. Contensive and compressive bandagings prolong the action of
lymphatic drainage. The main indication of manual physiotherapy is primary or
secondary lymphoedema but also chronic venous disease, and in some selected cases
acute venous thrombosis and traumatic or post-traumatic pains.
PMID- 11008501
TI - [Esthetic treatment of varicosities].
AB - Telangiectasia is dilatation of the subpapillary venous plexus of the epidermis
of the lower limbs, which can lead to aesthetic embarrassment. Before treating
telangiectasia, patient history and clinical examination help establishing its
origin. It can be with isolated, associated reticular drainage veins, or be part
of superficial venous insufficiency. Several types of treatment have been
proposed. Microsclerotherapy is the most effective and least costly. Muller's
phlebectomy can be performed when telangiectasia is fed by large reticular veins,
either afferent or efferent. Treatment by laser and pulsed light appear best
reserved to treatment of finer venous dilatations, either complementary or after
failure of sclerotherapy.
PMID- 11008502
TI - [Support and compression of the legs].
AB - Physical methods are essential in the treatment of venolymphatic insufficiency.
The available materials have two modes of action, support and compression; they
may be used alone or in association. Clinical experience and a few scientific
works formed the basis for establishing protocols adapted to each situation. Like
any major treatment, these should be under the full responsibility of physicians.
Prescriptions should be precise and, in particular, evaluated for each patient by
the physician himself.
PMID- 11008503
TI - [Heat therapy in chronic venous insufficiency of the legs].
AB - Water cures have long been advocated for venous and lymphatic disorders. Spa
therapy combines hydrotherapy, physical therapy and education. Immersion
increases central blood volume, diuresis and natriuresis. These effects are
independent of the mineral characteristics of the water. Hydrotherapy is viewed
as a complementary treatment of venous and lymphatic insufficiency whatever its
stage of development; but this has not been formally proved.
PMID- 11008504
TI - [Perils in the Americas: five commentaries and an editorial].
PMID- 11008505
TI - [Exophthalmos. Diagnostic orientation].
PMID- 11008506
TI - [Hypertension in pregnancy. Diagnosis, complications, treatment].
PMID- 11008507
TI - [Chronic delusions. Diagnosis, development, treatment].
PMID- 11008508
TI - [Gait disorders and falls in the elderly. Diagnostic orientation].
PMID- 11008509
TI - [Infectious mononucleosis. Epidemiology, diagnosis, development].
PMID- 11008510
TI - [Disorders of acid-balance balance. Physiopathology, diagnosis, treatment].
PMID- 11008511
TI - [Drug utilization. Different sectors and determining factors].
PMID- 11008514
TI - [Bovine herpes mammillitis: clinical symptoms and serologic course].
AB - Bovine herpes mammillitis was diagnosed in a dairy herd with udder and teat skin
lesions. Clinical symptoms seen in 6 cows consisted of round dry areas at the
teats as well as large red and painful areas with crust formation at the teats,
the teat basis and the udder. Diagnosis was verified by demonstrating numerous
virus particles with the typical herpes structure and by BHV-2 serum
neutralization test. Prevalence of BHV-2 in the herd was determined by using BHV
2 SNT at 7 occasions during a period of 15 months. The relatively low BHV-2 SNT
titres as well as the seasonal increase of BHV-2 titres and seroprevalence in the
month of September were indicative of a chronic and latent BHV-2 infection in the
herd.
PMID- 11008513
TI - [Ehrlichiosis in Switzerland--significance for veterinary medicine].
AB - Ehrlichiosis is a rickettsial disease of animals and humans caused by various
species of Ehrlichia. These obligate intracellular microorganisms infect
granulocytes or monocytes of mammalian hosts and are transmitted mostly by ticks.
The febrile disease is often undiagnosed and characterized by leukopenia, anemia
and thrombocytopenia. The diagnosis of ehrlichiosis is based on clinical
findings, tick infestation, direct or indirect detection of the agent, and
serology. The role of native and imported ehrlichiae of animals in Switzerland is
discussed.
PMID- 11008515
TI - [Prevention of pregnancy in bitches with the progesterone antagonist
anglepristone (alizone)].
AB - A study was carried out between April 1997 and October 1998 to determine the
effect of the progesterone antagonist, Aglepristone (Alizine), for the prevention
of pregnancy. 93 bitches were treated, because of mismating, with Aglepristone.
The owners were then contacted 2 weeks and 6 to 12 months after treatment to
gather any information on effects noted over this period. The major questions
were, was pregnancy prevented and if so what side effects were observed, if any,
and whether any metropathies were diagnosed. Also noted was the beginning of the
next heat and, if the bitch was mated, the fertility rate. Pregnancy was seen in
only one bitch. In 51 bitches minor side effects, either singularly or in
combination, such as a transient itch, vaginal discharge, reduced appetite,
tiredness or attachment were observed. The fertility was not influenced by the
treatment and the incidence of metropathies was unchanged.
PMID- 11008516
TI - [Isolation of Listeria spp. and Aspergillus fumigatus--two case reports from
mastitis diagnosis].
AB - Two rare cases of a bovine listeria mastitis and a mould mastitis are being
described and discussed. The L. monocytogenes strains isolated from milk as well
as silage samples were further genotyped by means of Pulsed-Field Gel
Electrophoresis (PFGE) and macrorestriction analysis (ApaI). Three strains from
the silage and four strains from quarter milking showed an identical PFGE
pattern.
PMID- 11008517
TI - [Torsio uteri as the differential diagnosis for gestational ketosis in sheep].
PMID- 11008518
TI - [Disintegration of the Nordic countries?].
PMID- 11008519
TI - [The Nordic countries--closest cooperators when it comes to research?].
PMID- 11008520
TI - [Social medicine should bite the dust!].
PMID- 11008521
TI - [A difficult problem without an easy solution].
PMID- 11008522
TI - [Tattooing--a cultural expression].
PMID- 11008523
TI - [Ophthalmology and cosmetics].
PMID- 11008524
TI - [A potential for prevention of bicycling-related head injuries].
AB - BACKGROUND: Bicycle helmets prevent head injury in bicycle riders. Still, only a
portion of bicycle riders in Norway use bicycle helmets. The aim of this study
was to estimate the number of head injuries among bicycle riders that might be
prevented by increased helmet use in Norway. MATERIAL AND METHODS: We used data
from the Norwegian National Injury Register for the years 1995 and 1996 to
estimate the number of bicycle injuries in Norway. In order to estimate the
number of bicycle users and helmet users in different age groups, we used data
from earlier surveys of bicycle use. Data on the effectiveness of helmet
promotion interventions have been obtained from a systematic review of the
literature. RESULTS: The overall annual incidence rate was 92 injuries per
100,000 bicycle users. The incidence varied with age and was highest among
children. If every rider used a helmet, about 1,600 head injuries would be
avoided every year, of these, 800 among children aged 0-14. Currently available
helmet promotion interventions may improve the use among children by about 40%,
thus preventing about 1,500 head injuries over a period of three years.
Successful helmet promotion interventions use a combination of health education
and helmet distribution strategies. INTERPRETATIONS: There is a significant
health improvement potential in promoting bicycle helmets in Norway by
implementation of evaluated modes of intervention.
PMID- 11008526
TI - [Centrally acting muscle relaxants and traffic hazards].
AB - BACKGROUND: An increasing number of the centrally acting muscle relaxants were
withdrawn from the Norwegian market during the 1988-98 period. The only drug in
this group now marketed in Norway is carisoprodol. The National Institute of
Forensic Toxicology in Norway analyses all blood samples from suspected drugged
drivers. In later years there has been a marked increase in the number of blood
samples testing positive for carisoprodol or meprobamate (the major metabolite).
MATERIAL AND METHODS: 480 cases testing positive for central muscle relaxants in
the years 1984-1998 were further studied. RESULTS: Compared with blood samples
positive primarily for benzodiazepines, there were more women in the group (39%
vs. 15%), and fewer drugs and less alcohol were detected. INTERPRETATION: The
positive samples may indicate misuse or abuse due to the fact that high drug
concentrations and concomitant use of benzodiazepines were frequent. This
knowledge should have implications for doctors prescribing centrally acting
muscle relaxants.
PMID- 11008525
TI - [Treatment of patients with acute head injury in Vestfold 1987-96].
AB - BACKGROUND: In Norway, patients with severe head injuries are transported to a
regional, neurosurgical department for surgery, but some are operated on by
surgeons without neurosurgical training in local hospitals. MATERIAL AND METHODS:
Data were retrospectively collected from the records of all patients (n = 161)
hospitalised alive with a severe head injury occurring within Vestfold County
(1987-96). RESULTS: Overall lethality was 27%. 54 patients (34%) underwent
decompressive surgery. 31 patients were operated in the local hospital, by 13
different surgeons. 30 of these patients had extracerebral haematomas. These
patients had a significantly worse outcome than the 23 patients operated in a
regional neurosurgical department. Patients with an epidural haematoma had a
better outcome than patients with an acute subdural haematoma. We retrospectively
classified ten operations in the local hospital as inadequate. INTERPRETATION: In
Norway and countries with a similar hospital system, local hospitals should
establish guidelines for safe and swift transport of head injury patients to the
nearest neurosurgical department, and should not try to perform neurosurgical
decompression in such patients.
PMID- 11008527
TI - [Evaluation by public health physicians of collaboration and workload within
municipal health services].
AB - BACKGROUND: We wanted to explore the quality and importance of the collaboration
between public health physicians and selected groups of professionals and
politicians. MATERIAL AND METHODS: The study was a cross-sectional survey based
on self-administered questionnaires with closed questions. Response came from 218
public health doctors who worked in the municipalities throughout the study
period (1988-91), and from 98 doctors who left public health during the same
period (81% and 86% of the study populations respectively). RESULTS: The doctors
reported good and important collaboration with other health professionals, but
less good and less important collaboration with other professionals and with
politicians. With increased administrative distance between the doctor and other
municipality staff, the perceived quality of the collaboration decreased.
INTERPRETATION: Closer collaboration between public health doctors and important
decision makers in the municipality promotes job satisfaction among doctors and
may reduce turn-over.
PMID- 11008528
TI - [Tryggve Gran--the first Norwegian heroic pilot].
AB - Tryggve Gran grew up in an affluent family in Bergen, Norway. The German emperor,
William II, often visited the families of his friends. Gran became a good skier,
hence well prepared for Robert Scott's second expedition to the Antartic in 1910.
Gran deeply regretted the Scott-Amundsen competition, and was cut off from the
team heading for the South Pole. In 1913, Gran trained in England and France as
an air pilot. On 30 July 1914 he became the first pilot to cross the North Sea
from Scotland to Norway. He joined the Royal Air Force in 1916 under the
pseudonym of Teddy Grant, passing himself off as a Canadian, and received the
Military Cross for distinguished war service. During the Second World War, Gran
was a member of Quisling's pro-German National Party. A commemorative stamp was
issued in 1944 on the 30th anniversary of his North Sea flight, and a meeting
held in his honour with Quisling and German officers present. In this article,
the author discusses some psychological aspects of Tryggve Gran's choice of tasks
and of his politics. Gran lost his father when he was only five and when he was
11 he was sent off to a pension in Switzerland for a year. Strongly ambivalent
feelings from the oedipal period and from the latency may later have been
released through hazardous activities, certainly with self-destructive aspects.
His membership in Quisling's party might be seen in this context.
PMID- 11008529
TI - [Sound and unsound around the Sound. A congress report on health differences
between Denmark and Sweden].
AB - During the past 10 years, researchers on both sides of The Sound in the so-called
Oresund region have worked together to analyze the causes of the observed
differences in life expectancy between Denmark and Sweden. The region includes
Copenhagen and North Zealand and the county of Scania in southern Sweden, with
Malmo as its largest city. Both Denmark and Sweden held top rankings among OECD
countries in 1970 regarding life expectancy at birth. In 1990 Denmark had fallen
to a bottom ranking, while Sweden was still at the top. At a scientific meeting
in Malmo on January 26-27, 2000, some 60 presentations were made concerning
differences and similarities in health measures on the two sides of the sound
which divides the two countries. On the Swedish side, life expectancy is 3-4
years longer than on the Danish side. Paramount among explanations are higher
mortality figures due to smoking and alcohol-related diseases on the Danish side,
both in men and women (most pronounced). Minor contributions to the differences
are suicides and traffic accidents. Historically, Denmark and Sweden have much in
common. Until 1658, Scania, the Swedish county to the east of The Sound was part
of Denmark. During the past 150 years rather impressive cultural differences have
developed. Smoking prevalence and alcohol consumption are more than twice as high
on the Danish side of the sound. In coming years, researchers, representatives
for the health service systems and others will work together in order to prevent
disease and promote health in the Oresund region. The conference was arranged by
the Medicon Valley Academy, an EU-supported enterprise seeking to stimulate
research and development within the health sector in the Oresund region (also
known as Medicon Valley).
PMID- 11008530
TI - [Scandinavian guidelines for management of minimal, mild and moderate head
injuries].
AB - The Scandinavian Neurotrauma Committee (SNC) was initiated by the Scandinavian
Neurosurgical Society to develop evidence-based guidelines for improved care of
neurotrauma patients. A MEDLINE search identified 475 papers dealing with the
management of minimal, mild and moderate head injuries. Fourty-two studies
presenting Class II evidence on the initial management of such injuries were
reviewed and management guidelines were developed. Implementation of the Head
Injury Severity Scale is advocated. Patients with minimal injuries (no loss of
consciousness (LOC), Glasgow Coma Scale (GCS) score 15) can be safely discharged.
Routine early CT scan is recommended in cases with mild injuries (history of LOC,
GCS 14-15) and patients with normal scans may be discharged. CT scan and
admission is mandatory in moderate injuries (GCS < or = 13). All patients
harbouring additional risk factors should be scanned and admitted. A flow chart
for clinical decision making and a Head Injury Instruction card are introduced.
PMID- 11008531
TI - [Norwegian tourists' use of medical services abroad].
AB - BACKGROUND: Previous studies have shown that one in three holidaymakers
experienced illness on their trip abroad. We wanted to find out what happens to
Norwegian tourists. MATERIAL AND METHODS: We have collected data from the
Association of Norwegian Tour/Operators on travel patterns, and from a travel
insurance company on illness and expenses. RESULTS: Between 1.5% and 5% of
travellers get so ill that they need medical assistance. The number of
consultations that results in hospitalisation vary from less than 5% in one
country to more than 30% in neighbouring territories. Average cost of
hospitalisation differ considerably from one country to another. INTERPRETATION:
It appears that cultural differences, differing treatment facilities, and varying
required rates of return are decisive for whether or not a patient is referred to
hospital.
PMID- 11008532
TI - [Long term effects o gastric banding for weight reduction].
AB - BACKGROUND: Obesity is defined as body weight exceeding normal weight by 30%, or
a body mass index (BMI) > 30. Various surgical procedures have been introduced to
treat obesity. Gastric banding is a variant of the gastroplastic method. Our aim
was to study the long term effect of this procedure. MATERIAL AND METHODS: Over
the years 1982 to 1988, gastric banding was performed at the county hospital of
Haugesund in 26 patients with a mean age of 35.7 years and a mean preoperative
BMI of 41.2. Data were obtained from patient files and from questionnaires
returned by 24 patients, on average 14 years after the operation. RESULTS: Mean
BMI for 16 patients with an intact banding device at follow-up was 35.2. Mean
weight reduction was 15 kilograms. 58% of the patients regretted the procedure.
Only a few were completely satisfied. INTERPRETATION: Long term results of
gastric banding are not satisfactory.
PMID- 11008533
TI - [The obesity epidemics--do diet pills have a place in the treatment?].
AB - BACKGROUND: Many experts consider obesity a chronic disease that may require long
term therapy. A loss of 5-15% of body weight is associated with improvements in
cardiovascular risk factors and morbidity. However, most studies show that the
majority of patients who lose weight relapse. Patients may be unable to maintain
a low energy intake when confronted with an almost limitless supply of food.
Moreover, a number of physiological mechanisms favour a set point for body
weight, that may be altered with anti-obesity drugs. MATERIAL AND RESULTS: In the
current paper we describe actions and effects of current anti-obesity drugs. The
centrally acting drug, sibutramine, is an adrenaline and serotonine re-uptake
inhibitor which was recently approved in the USA for obesity. The USA, the
European Union and Norway have approved orlistat, a pancreatic lipase inhibitor
for weight reduction for up to two years. Patients must maintain a low fat intake
in order to avoid gastrointestinal discomfort. In recent studies, orlistat and
diet reduced body weight by 9% versus 6% on placebo and diet. No studies have
documented long-term safety of anti-obesity drugs. INTERPRETATION: Treatment of a
lifestyle-related disease like obesity with medications is controversial,
however, such treatment may not differ substantially from treatment of type II
diabetes, hyperlipidaemia or hypertension.
PMID- 11008534
TI - [Is the benefit of organized mass screening for cervix cancer and breast cancer
in Norway scientifically justified?].
AB - BACKGROUND: It has been argued that mass screening may reduce mortality from
cervical cancer and breast cancer in Norway by 50% and 39%, respectively.
However, some authors doubt that mass screening for breast cancer is justifiable.
This article discusses whether mass screening for cervical cancer in Norway is
more effective than opportunistic screening. MATERIAL AND METHODS: The scientific
methods used to justify organised mass screening for cervical cancer are reviewed
and discussed, as are the randomised trials used to justify screening by
mammography. The author is especially critical of the use of descriptive
statistics to justify screening, on the assumption that there is a basic constant
incidence or mortality rate. RESULTS: The incidence rates of pre-malignant
conditions and cervical cancer in Norway are presented. There is no essential
increase in the number of pre-malignant conditions after three years of organised
mass screening compared to the previous three-year of unorganized screening.
However, the number of pre-malignant conditions did increase from 1987 to 1992
due to a national recommendation for testing every three years. By contrast,
incidence rates for cervical cancer remained almost constant in the 1987-97
period. INTERPRETATION: There is no scientific proof of organised mass screening
for cervical cancer being preferable to unorganized screening. The author warns
against only comparing observed rates with historic rates and rates in other
countries; alternatively, rates among those who participate in the screening
might be compared in a simultaneous analysis to rates among those who do not
respond to the invitation. The author also suggests estimating correlation
coefficients between individual test results to identify high-risk individuals.
PMID- 11008536
TI - [Painful neuropathies].
PMID- 11008535
TI - [Subacute abdominal pain in a very old woman].
PMID- 11008537
TI - [Gastric lavage and activated charcoal in acute poisonings].
PMID- 11008538
TI - [What is specifically Nordic in medicine?].
AB - Nordic health professionals often hear the term "the Nordic model" when visiting
countries outside the Nordic area. This Nordic model is usually related to
selected aspects like the doctor-patient-relationship, the structures and
functions of the Nordic health systems, and the independent, nationwide control
systems in the Nordic countries which deal with research ethics and integrity in
research within the biomedical sciences. In this essay the concept of
specifically Nordic characteristics within medicine and health services is
evaluated through an observation window. The conclusion is that the most
components of the Nordic health sectors, including education and research, are by
their very nature global, but that their weighting and the projection to clinical
work and research show decisive traits, especially related to patients' rights
and ethics. On this background, it seems legitimate to accept the surrounding
world's impression of a special Nordic model.
PMID- 11008539
TI - [Differences in health status--policy, life style and genes].
AB - BACKGROUND: The five Nordic countries seem rather homogeneous when assessed from
abroad. They do have a lot in common: similar political systems, same standard of
living, and even a common language root for a large part of the population. The
Nordic countries have collaborated quite closely after the Second World War in
fields like the labour market, pension rights and passport control. However, the
health status has varied considerably during the twentieth century, even though
death rates from some of the most common diseases such as cardiovascular disease
are starting to converge. MATERIAL AND METHODS: Vital statistics have been
compared with regard to some common diseases. The differences are described
according to current knowledge on preventive programmes such as breast cancer
screening and screening for cardiovascular risk. The prevalence of some lifestyle
variables such as alcohol, smoking, physical activity and fat consumption are
reported. RESULTS AND INTERPRETATION: Lung cancer and cancer of the stomach still
show substantial variation between the countries. Both discrepancies and
similarities must be related to lifestyle, culture, politics and to some extent
genetics. The five countries have their own viewpoints on tobacco, alcohol and
nutrition policy, with the Danes the more liberal, and Swedes, Finns and
Norwegians pursuing a stricter policy. These differences are to some extent
reflected in the incidence of lung cancer, which are more positive in Finland,
and the high death rates from liver cirrhosis in Denmark. The relatively
unsatisfactory development in Denmark may be a consequence of a much longer
period of structural unemployment than the other countries, as well as a more
liberal attitude towards alcohol and smoking.
PMID- 11008540
TI - [Health care systems in the Nordic countries--more similarities than
differences?].
AB - The aim of this paper is to explore similarities and differences of the Nordic
health care systems. The analysis is based on a three-part model involving
patients, providers and the financing third party. In all Nordic countries, about
80% of the funding come from public sources. In Iceland, central government is
providing most of the health care services, while the county councils are central
in Denmark, Norway and Sweden. In Finland, the municipalities are providing most
of the health care. Salary is the only payment system for general practitioners
in Iceland, while it is used for some GPs in Finland, Norway and Sweden.
Capitation in combination with service fees is used for all Danish GPs and the
majority of the Finnish, while various fee-for-service systems are used for the
others. All Nordic countries had global hospital budgeting in the 1980s; since
then, Finland, Norway and Sweden have implemented others systems, predominantly
combinations of diagnosis-related group financing and global budgets. The amounts
of resources devoted to health care are about the same in all five countries
whether measured by the proportion of GDP devoted to health care, or by hospital
beds or doctor/patient ratios. In monetary terms, Denmark, Iceland and Norway
spend more than Finland and Sweden. Despite similar amounts of resources, they
are quite differently used across the countries. Differences of a factor of two
or more are observed for hip operations, gal bladder operations and
pharmaceuticals. Danes and Finns are very satisfied with their health care
system; the Swedes are not. All the Nordic countries have increased patient co
payments during the 1990s. Finnish patients may pay an extra free to get a one
bed room. Finland also has the greatest number of private hospitals. Despite all
these differences, the Nordic health care systems are quite similar when seen in
a global perspective.
PMID- 11008541
TI - [The manpower market for physicians in the Nordic countries 1980-2000].
AB - The ratio between population and active physicians in the Nordic countries has
improved from 488 inhabitants per physician in 1980 to 315 in 2000. There is a
large mobility of physicians between the countries, contributing to levelling out
swings in demand and supply of manpower. Language and culture being similar,
physicians can easily adjust to working in a neighbouring country. Iceland is
special in this respect, as a surplus of Icelandic physicians has always found
work in the other Nordic countries. Of course, their numbers are small relative
to the total number of active physicians in the Nordic countries, now
approximately 76,000. The number of students admitted to Nordic medical faculties
has changed in line with swings in estimated future demand for manpower. Today,
numbers are increasing again; this year, approximately 2,900 students will be
admitted. Norway stands apart from the other Nordic countries in terms of medical
manpower needs. During the last 20 years there has been a continuous shortage of
physicians while all the other countries have been through periods of surplus and
unemployment among physicians. Manpower forecasts in the early 1980s
underestimated the growth in the health care system and hence the demand for
medical manpower.
PMID- 11008542
TI - [Continuing education in the Nordic countries].
AB - The Nordic Labour Market Agreement gives Nordic medical specialist the right to
be certified in the other Nordic countries. The agreement also provides for
cooperation on specialist training between the five countries. This article is
mainly based on published statements from the joint working group for medical
manpower forecasts and specialist training in the Nordic countries. There are
great differences between the countries in the way specialist training is
organised. An underlying assumption in the Nordic agreement is that the level and
quality of specialist training is the same in all five countries; however, there
does not seem to be a corresponding coordination between the training systems
adopted.
PMID- 11008543
TI - [Surgery of strabismus--"cosmetic indication"?].
PMID- 11008544
TI - [Is carisoprodol justified as a muscle relaxant?].
PMID- 11008545
TI - [Physicians and alcohol--differences between the Nordic countries?].
PMID- 11008546
TI - [Whistleblowers--are they "difficult persons"--or are they forced to be
difficult?].
PMID- 11008547
TI - [Hospital ship--it's there when needed].
PMID- 11008548
TI - [Greetings from the Mecca of epidemiology].
PMID- 11008549
TI - [Norwegian health services as seen from Stockholm].
PMID- 11008550
TI - [Ultrasonography early in pregnancy].
PMID- 11008551
TI - [The National Board of Health and Welfare recommends an inefficient method].
PMID- 11008552
TI - [X-Ray upper airway changes in individuals suffering from obstructive respiratory
disorders during sleep].
AB - Obstructive respiratory disorders during sleep present an important medical and
social problem. Serious dysfunctions of cardiovascular, nervous, endocrine and
other vital systems of the body reduce longevity and life quality. On the other
hand, load nocturnal snore and abnormal diurnal sleepiness cause great damage to
family life, reduce working capacity and induce accidents. X-ray visualization of
the upper airways is essential in diagnosing obstructive upper airway states and
selecting patients for surgical treatment. The paper presents the authors' own
experience in using various X-ray diagnostic methods in patients with chronic
snore and obstructive sleep apnea-hypopnea syndrome.
PMID- 11008553
TI - [Radiation diagnosis of Langerhans cell histiocytosis (LCH) of lung].
AB - The authors studied the pattern of X-ray changes detectable in the lungs of 41
patients with LCH. The results of classical X-ray study were supplemented by the
data of computed tomography, ultrasonography, and 99mTc and 67Ga citrate
radioisotopic studies. The diagnostic values of these techniques were compared. X
ray syndromes of changes in the lung in LCH were found to be interstitial,
interstitial and granulomatous, tumorous (focal). The authors emphasize the
multisystematic character of a lesion, the phasic nature and progression of the
disease into fibrosis.
PMID- 11008554
TI - [Chronic occlusions in patients with coronary heart disease: results of
recanalization].
AB - The paper analyzes the results of endovascular treatment in 298 patients with
chronic occlusions or subtotal stenoses of coronary arteries. The authors show
that balloon coronary angioplasty for chronic coronary occlusions is an effective
and relatively safe techniques of myocardial revascularization. Successful
endovascularization has been achieved in 68.1% of patients with chronic coronary
occlusions and in 97.5% of those with subtotal coronary stenoses. The results
show a high incidence of restenosis and asymptomatic reocclusion.
PMID- 11008555
TI - [Use of radial artery as an access during coronary angiography: experience and
further prospects].
AB - The authors present their own experience in using the radial artery for
diagnostic coronarography. Twenty two transradial studies were made during a year
and a half. Following the studies, complications were as follows: failure at
puncture in 1 (4.5%) patient, local and cardial complications being absent. The
authors concluded that the radial access is a promising alternative to the
routine femoral one now. The use of the radial access opens up new vistas for
coronary angiography performed in the outpatient setting, by making this
technique accessible to patients with coronary heart disease who need to be
thoroughly studied.
PMID- 11008556
TI - [Interventional radiology in congenital and acquired cardiovascular diseases].
AB - The paper outlines the present-day achievements in interventional radiology in
cardiovascular diseases: balloon valvuloplasty in cardiac diseases (isolated
pulmonary arterial stenosis, aortic and mitral stenosis), balloon vasodilatation
(peripheral pulmonary arterial stenosis, aortic coarctation), embolization of the
vessels and pathological communications, atrioseptostomy, transcatheter closure
of atrial septal defects.
PMID- 11008557
TI - [Current approach to treating borderline coronary stenosis: clinical case].
PMID- 11008558
TI - [Up-to-date positions of prophylactic fluorographic examinations of chest (review
of literature)].
PMID- 11008559
TI - [Radiation diagnosis of biliary system before laparoscopic cholecystectomy. Part
II: non-ultrasonic techniques].
PMID- 11008560
TI - ["Diamag" is a new magnetic resonance tomograph ("Az" firm)].
PMID- 11008561
TI - [To applicability of foreign medical radiographic films during various
chemophotographic treatments].
PMID- 11008562
TI - [Recovery processes in the cerebral cortex, myocardium and thymus of rats with
experimental atherosclerosis exposed to low-frequency electromagnetic fields on
the head].
AB - Studies of animals with experimental sclerosis has shown that a course of 10
procedures of alternative magnetic field (AMF) (50 Hz, 30 mT, 3 min daily)
promotes partial recovery of the lipid spectrum and corrects vasomotor-metabolic
disturbances in the cerebral cortex, myocardium and thymus caused by
atherosclerosis. Combination of AMF with constant magnetic field in the same
regime and location does not produce a hypolipidemic effect in atherosclerotic
animals and this, in combination with increased vascular permeability may
aggravate the condition. Activated microcirculation, antioxidant and
antiproteinase effects in activation of biosynthetic processes in the cerebral
cortex reflect inhibition in the CNS in this combined effect and create
conditions for a hypotensive effect.
PMID- 11008564
TI - [The combined effect of potable mineral waters and mid-alpine factors on hormonal
status (clinico-experimental research)].
AB - Hormonal status was examined in 30 intact male Wistar rats (body mass 200-220 g)
and 10 healthy male volunteers aged 25-35 years. Hormonal status and influence of
exercise were assessed in human males after 2, 10 and 19 days of stay in the
sanatorium situated 2000 m above the sea level. The animals were decapitated on
day 24 of their stay in the mountains. Blood from the rats' cervical vessels was
examined for glucose, beta-lipoproteins, triiodothyronine, thyroxine, TTH,
hydrocortisone. The findings indicate that stay in conditions of medium-height
mountains climate aroused adaptation reactions in the hormonal systems, i.e.
activation of thyroid hormones. An additional course of mineral water contributed
to further rise of the blood hormones. Hormonal trends in the volunteers were
similar. There was also a rise in the levels of beta-lipoproteins which was
arrested by physical exercise.
PMID- 11008563
TI - [Pain relief by low-intensity frequency-modulated millimeter waves acting on the
acupuncture points].
AB - Analgetic effect of low-intensive frequency-modulated millimetric waves (MW) was
studied in mice with formalin induced nociceptive behavior reaction (licking of
defeat hindpaw). MW were applied to the acupoint E 36 of the defeat hindpaw. The
following MW were used: 60 GHz (1) and 118 GHz (2) which were modulated by 4 Hz;
noise MW within the range of 42-95 GHz (3) and 90-140 GHz (4) which were
modulated in accidental order by frequencies 1-60 Hz; combinations of fixed
frequencies with noise - 60 GHz + noise 42-95 GHz (5) and 118 GHz + noise 90-140
GHz (6). All used MW combinations suppressed licking of the defeat hindpaw and
increased duration of sleep and eating. The strongest analgesia was achieved in
series 1-3 (42.4-69.7%), the weakest in series 6 and 4 of the experiment (12.2
19.7%).
PMID- 11008565
TI - [An evaluation of the effect of sodium bicarbonate-chloride mineral water on the
rat immune system].
AB - Mineral water Uralochka tried in rats is obtained from the spring in the
territory of the sanatorium Ural (Chelyabinsk Province). The mineral water
contains chloride, hydrocarbonate ions and sodium cations, mineralization is 4.13
g/dm3. A 15-day course of Uralochka drinking did not influence much reaction of
delayed hypersensitivity, but increased the absolute number of antibody-forming
cells by 95.86%, raised the ability of peritoneal macrophages to absorb latex
particles. Thus, mineral water Uralochka can raise intensity of humoral immune
response and the ability of macrophages for phagocytosis of the latex particles.
Phagocytosis activity and intensity increased by 48.27 and 62.13%, respectively.
PMID- 11008566
TI - [Carbonate mineral baths in the combined treatment at a piedmont health resort of
patients operated on for rheumatic heart defects].
AB - The response of the cardiovascular system of 64 patients operated for rheumatic
heart disease to mineral carbon dioxide baths was studied in the course of
rehabilitation in low-mountain health resort. It was found that the above baths
have a training effect on the cardiac muscle, improve myocardial metabolism. They
are an essential factor in combined sanatorium treatment of patients after
surgical correction of valvular defects. Baths-induced changes in the central and
peripheral hemodynamics depend on cardiovascular function. Therefore, they
require an individual approach. If the exposition increases to 15 minutes,
mineral carbon dioxide baths have more potent training effect on the myocardium
and raise effectiveness of the sanatorium treatment.
PMID- 11008567
TI - [The efficacy of combined treatment in patients with chronic mycotic bronchitis
using baro-laser therapy].
PMID- 11008568
TI - [The methodological aspects of using cryomassage on patients operated on for
discogenic neuropathies].
AB - Cryomassage in combined treatment of 100 patients operated for discogenic
neuropathy produced a pronounced vasotropic effect. The authors have determined
optimal zones for cryomassage application and order of its usage with some
physical factors.
PMID- 11008569
TI - [The use of physical factors in the rehabilitative treatment of patients with
stone fragments in the upper urinary tract after extracorporeal shockwave
lithotripsy].
AB - 155 patients with fragments of the crushed stones in the upper urinary tract
after lithotripsy were divided into 3 groups. 60 patients of group 1 received
dynamic amplipulse therapy, oral mineral water, iodobromine baths. Elimination of
the fragments was observed in 91.7% of the patients. Group 2 patients (n = 60)
were exposed to local vibration, ultrasound and iodobromine baths. The effect
occurred in 96.7% of the cases. 35 patients of group 3 were exposed to impulse
low-frequency magnetic field and took iodobromine baths. The elimination of the
fragments occurred in 62.9% of the cases after a single treatment course.
PMID- 11008570
TI - [The combined use of pelotherapy, ultrasound and sinusoidal modulated currents in
chronic prostatitis and proctosigmoiditis].
PMID- 11008571
TI - [A comparative assessment of different cryotherapy methods for patients with
chronic nonspecific salpingo=oophoritis].
AB - 97 females at reproductive age with chronic nonspecific salpingo-oophoritis
(CNSO) were examined and treated. The results of the treatment (vaginal and
external impact) demonstrate positive effects of various cryotherapeutic
techniques on CNSO clinical course, on hormonal and immune unbalance, functional
activity of the uterine tubes, regional hemodynamics, psychoemotional status.
Thus, cryotherapy is an effective adjuvant in combined therapy of CNSO.
PMID- 11008572
TI - [An experimental and clinical validation of a method for treating acute
inflammatory diseases of the adnexa uteri by using the electrophoresis of a
therapeutic mud preparation].
AB - Experimental and clinical investigations have demonstrated that the addition of
abdominal-sacral electrophoresis of esobel 1% solution to combined therapy of
acute inflammation of the uterine appendages improves treatment results.
Bioantioxidants bring about the antiinflammatory action of the mud preparation
esobel while its high-polar lipids prevent structural-metabolic impairment of the
appendages' tissue elements as shown by a pronounced antiexudative effects and
weak secondary alteration.
PMID- 11008573
TI - [The new potentials of magneto-laser therapy and electrostimulation in children
with cleft palate and upper lip].
AB - The paper presents rationale for design of new procedures of physiotherapy in
children with expanded palate and upper lip; morphofunctional features of
prenatal and early postnatal formation of central nervous system; a multilayer
technique of magneto-laser radiation to the projection of the anterior central
gyrus and the technique of electrostimulation by the system of the wink reflex
which can influence central mechanisms of regulation and adaptation before and
early after uranoplasty and cheiloplasty.
PMID- 11008574
TI - [The sauna in the treatment of children with atopic dermatitis].
AB - Complex sauna therapy for children with atopic dermatitis gives positive clinical
results and improves the condition of their autonomic nervous system. Marked
clinical response but unsatisfied autonomic nervous system regulation necessitate
long-term sauna treatment to cure this disease.
PMID- 11008575
TI - [The health resort and recreational potential of Moscow Province].
PMID- 11008576
TI - [The regulation of the sanatorium-health resort market].
PMID- 11008577
TI - [Endonasal electrophoresis in ophthalmology].
PMID- 11008578
TI - [The biorhythmological regulation of external breathing in bronchial asthma
patients by using intermittent normobaric hypoxia therapy].
PMID- 11008579
TI - [The treatment of ENT diseases in children of the indigenous nationalities of the
North with local mineral waters from Zavodoukovski spring].
PMID- 11008580
TI - [The use of hydrocortisone combined with ultrasound with gonarthrosis patients].
PMID- 11008581
TI - [A patent review on the problem of the transfer of the informational properties
of therapeutic factors].
PMID- 11008582
TI - [The effect of physical factors on the skin permeability of normal white rats and
in the modelling of pathological processes].
PMID- 11008583
TI - African trypanosomiasis, tuberculosis and dengue research.
PMID- 11008584
TI - American Society of Critical Care Anesthesiologists 13th annual meeting. San
Francisco, California, USA. October 13, 2000. Abstracts.
PMID- 11008585
TI - Psychotropic drugs and preschoolers.
PMID- 11008586
TI - Ischaemic heart disease: across the social and geographic divides.
PMID- 11008587
TI - SIDS: facts and controversies.
PMID- 11008588
TI - Falls in the elderly: what can be done?
PMID- 11008589
TI - Characteristics and outcomes of older patients presenting to the emergency
department after a fall: a retrospective analysis.
AB - OBJECTIVES: To study older patients presenting to the emergency department after
a fall--factors associated with the fall, injuries sustained and outcome. DESIGN:
A retrospective analysis using the Emergency Department Information System
(EDIS), the Trauma Registry and the patient information database (CCIS), in
addition to the patient's emergency and inpatient medical records. SETTING:
Emergency department of a major inner city teaching hospital, 1 June-30 November
1997. PATIENTS: All patients over 65 years presenting to the emergency department
(ED) after a fall, for whom complete medical records were available. RESULTS: Of
803 patients over 65 years presenting to the ED after a fall, complete records
were available for 733 (91.3%) (283 men and 450 women). Extrinsic (accidental)
causes were implicated in more than a third of falls (313 patients [42.7%]). A
high proportion of the patients were living at home (520; 70.9%) and walking
unaided (389; 53.1%). Although absolute numbers of women increased with age, men
were as likely as women to present after a fall. Many patients had fallen before-
39% of the men (111/283) and 24% of the women (110/450). In 78 patients (10.6%),
alcohol misuse may have been a direct cause of the fall. The overall injury rate
was 70.5% (517/733 patients), the most common injury being an isolated fracture
(269/517 patients; 52.0%). In all, 419 patients (57.2%) were admitted to
hospital, 48% (200/419) with a fracture and 52% (219/419) for investigation of
the medical cause of the fall. The median length of hospital stay was 6 days
(mean, 10.4 days; range, 1-129 days); 35% (146/419) of patients were in hospital
for more than 10 days. CONCLUSION: Older patients presenting to the ED after a
fall had high injury rates, high admission rates and often prolonged
hospitalisation. About a third had fallen before. Patients at risk can be
identified in the ED and referred to falls prevention programs.
PMID- 11008590
TI - Predictors of bone mass in healthy older men in the community.
AB - OBJECTIVES: To determine the predictors of bone mass (in lumbar spine and femoral
neck) in healthy older men living in the community. DESIGN: Cross-sectional
study. Bone mineral density (BMD) was measured and known predictors of bone mass
and bone turnover were assessed. SUBJECTS AND SETTING: 113 independent, healthy
men (70 years and over), not taking glucocorticoid therapy and without medical
conditions known to affect bone mass and bone turnover, were recruited from
recreational and sports clubs in southern Sydney in April/May 1997. MAIN OUTCOME
MEASURES: BMD (measured by dual-energy x-ray absorptiometry); known predictors of
bone mass (height; weight; body mass index; calcium level; serum 25
hydroxyvitamin D and free testosterone levels); and markers of bone turnover
(serum bone Gla protein and procollagen-1 concentrations, and urinary
deoxypyridinoline excretion rates). RESULTS: The mean age of the men was 76.6
years (range, 70-92 years). Mean (SE) BMD of the lumbar spine was 1.143 (0.019)
g/cm2 and that of the femoral neck was 0.897 (0.013) g/cm2. BMD values indicating
osteoporosis were found in the lumbar spine in 13 men (11.5%) and in the femoral
neck in 35 men (31%). The best predictor of lumbar spine BMD was weight (R =
0.37; P = 0.001), and weight- and age-predicted femoral-neck BMD (R = 0.49; P <
0.001). The study group was analysed in two groups with BMD higher or lower than
median bone mass corrected for age. Men with lower femoral-neck BMD for age had
significantly lower weight, lower lean mass and higher bone Gla protein
concentrations. In addition, men with lower lumbar spine BMD for age also had
significantly lower fat mass. CONCLUSIONS: These data indicate that measures of
body composition, such as weight and lean mass, are the main predictors of bone
mass in healthy, community-dwelling older men.
PMID- 11008591
TI - Prevalence of Huntington disease in New South Wales in 1996.
AB - OBJECTIVE: To estimate the prevalence of Huntington disease (HD) in New South
Wales on Australian Census Day (6 August) 1996. DESIGN: Survey of records of the
Huntington Disease Service and major hospitals, and of neurologists,
psychiatrists, clinical geneticists and genetic counsellors. SUBJECTS AND
SETTING: All patients in NSW who, on Census Day 1996, either had a definite
diagnosis of HD (motor signs of chorea or ataxia and family history of HD or
positive DNA test result) or would have had signs and later received a definite
diagnosis (assessed 1 April 1997 to 1 July 1999). MAIN OUTCOME MEASURES:
Prevalence (HD patients per 100,000 population); patient characteristics; year
and basis of diagnosis. RESULTS: 380 patients with definite HD were identified,
giving a prevalence of HD in NSW in 1996 of 6.29 per 100,000 population (95% CI,
5.68-6.96). A third of HD patients were aged 60 years or older. Diagnosis was
confirmed by DNA testing for 171 patients (45%), including 30 (8%) with no
recorded family history. Average numbers of new diagnoses per year were 11.8
(1984-1988), 21.8 (1989-1993) and 28.6 (1994-1998). Estimated number of people
with a 50% risk of inheriting the HD mutation was 25.2 per 100,000 population.
Estimated incidence of HD in 1996 was 0.65 per 100,000 population. CONCLUSIONS:
Prevalence of HD in NSW is similar to estimated prevalence in other Australian
and Western populations. Increasing numbers of cases are being diagnosed, and the
18 chronic care beds currently designated for HD patients in NSW are unlikely to
be sufficient.
PMID- 11008592
TI - Driveway motor vehicle injuries in children.
AB - OBJECTIVES: To describe the frequency, nature and outcome of driveway injuries in
children. DESIGN: Retrospective case series of driveway-related injuries in
children under 16 years of age admitted to the New Children's Hospital (NCH), New
South Wales, from November 1995 to February 2000, and deaths reported to the New
South Wales Paediatric Trauma Death (NPTD) Registry from January 1988 to December
1999. MAIN OUTCOME MEASURES: Circumstances of injury; type and number of injuries
identified. RESULTS: 42 children were admitted to our institution with driveway
related injuries over four years and four months. These represent 12% of all
children admitted with pedestrian motor vehicle injuries. Fourteen deaths
(including one of the children admitted to NCH) were reported to the NPTD
Registry over 12 years, accounting for 8% of all paediatric pedestrian motor
vehicle deaths reported to the registry. Typically, the injury involved a parent
or relative reversing a motor vehicle in the home driveway over a toddler or
preschool-age child in the late afternoon or early evening. Four-wheel-drive or
light commercial vehicles were involved in 42% of all injuries, although they
accounted for just 30.4% of registered vehicles in NSW. These vehicles were
associated with a 2.5-times increased risk of fatality. In 13 of the 14 deaths,
the cause was a severe head injury not amenable to medical intervention.
CONCLUSIONS: Driveway injuries in children account for a significant proportion
of paediatric pedestrian motor vehicle injuries and deaths in NSW. Prevention
represents the only effective approach to reducing deaths from this cause.
PMID- 11008593
TI - Wasp sting mortality in Australia.
AB - Wasp sting fatalities have rarely been reported in Australia. We used data from
the Australian Bureau of Statistics and State coronial authorities to investigate
deaths from wasp stings in Australia from 1979 through 1998. Seven cases were
identified, all involving men in rural settings. Five of the seven victims had
prior histories of wasp or bee venom allergy, or both, but none carried
injectable adrenalin. All patients with a history of systemic Hymenoptera sting
allergy should undergo assessment for immunotherapy and carry adrenalin.
PMID- 11008594
TI - Delay times and management of acute myocardial infarction in indigenous and non
indigenous people in the Northern Territory.
AB - OBJECTIVES: To investigate differences in presentation and management of
Indigenous and non-Indigenous patients hospitalised with acute myocardial
infarction (AMI). DESIGN: Retrospective review of hospital medical records.
PARTICIPANTS AND SETTING: 122 patients with definite or possible AMI admitted to
hospitals in the Top End of the Northern Territory (NT) in 1996. MAIN OUTCOME
MEASURES: Percentage receiving thrombolytic therapy; delays from symptom onset to
primary and emergency department presentations, first and diagnostic
electrocardiograms, thrombolytic therapy and aspirin; drugs prescribed during
hospitalisation. RESULTS: Thrombolytic therapy was given to 12/41 Indigenous
patients (29%) and 38/81 non-Indigenous patients (47%) (P = 0.06). Presentation
delay over 12 hours was the reason for not giving thrombolytic therapy for 14/29
Indigenous patients (48%) and 8/43 non-Indigenous patients (19%) (P < 0.01).
Median delay times were longer for Indigenous patients for all six categories of
delay, although the difference was significant only for delay to emergency
department presentation (10:00 versus 3:26 hours; P < 0.01) and to diagnostic
electrocardiogram (8:10 versus 3:50 hours; P < 0.01). Delays were also longer for
patients from rural compared with urban areas. Once diagnosed, Indigenous
patients were as likely as non-Indigenous patients to receive aspirin (93% versus
96%) and beta-blockers (70% versus 69%) and more likely to receive angiotensin
converting enzyme inhibitors (60% versus 40%; P = 0.03). CONCLUSIONS: Delays in
presentation affect Indigenous people living in rural and urban areas as well as
non-Indigenous people living in rural areas. Concerted efforts are needed to
improve health service access in rural areas and to encourage Indigenous people
with persistent chest pain to present earlier.
PMID- 11008595
TI - Imagined ugliness: a symptom which can become a disorder.
AB - Concern regarding physical appearance is normal, but can sometimes reach an
intensity which renders it a "disorder" (body dysmorphic disorder, or BDD). The
rate of BDD in the general population is not clear, but sufferers are over
represented in psychiatric populations and in those seeking cosmetic surgery. BDD
shows extensive psychiatric comorbidity, including depression, social phobia, and
obsessive-compulsive disorder. BDD is treatable, with serotonergic
antidepressants (e.g., selective serotonin reuptake inhibitors) and cognitive
behavioural treatments being the most effective.
PMID- 11008596
TI - The clinical role of quantitative ultrasound in assessing fracture risk and bone
status.
AB - Quantitative ultrasound (QUS) analysis of calcaneal bone is useful to quantify
fracture risk, and in monitoring response to treatment and identifying bone
changes associated with disease and medication. However, diagnosis of
osteoporosis by QUS measurements remains contentious, but the problems are due to
the limitations of the present T-scores rather than the technique. QUS offers the
potential for the widespread detection of low bone mass and subsequent management
and prevention of fracture.
PMID- 11008597
TI - The new health insurance rebate: an inefficient way of funding public hospitals.
PMID- 11008598
TI - Use of diagnosis codes to understand variations in hysterectomy rates: a pilot
study.
PMID- 11008599
TI - Aeromonas hydrophila infection secondary to an electrical burn.
PMID- 11008600
TI - The hospitalist: a third alternative.
PMID- 11008601
TI - Use of antibiotics in the management of prelabour rupture of the membranes at
term.
PMID- 11008602
TI - Universal periconceptional folate supplementation: chasing a dream?
PMID- 11008603
TI - The Declaration of Helsinki and research in vulnerable populations.
PMID- 11008604
TI - Caring in healthcare.
PMID- 11008605
TI - Is there a place for a graduate entry medical course in New Zealand?
PMID- 11008606
TI - Inequalities: a challenge to science and politics.
PMID- 11008607
TI - Plastic wrapping of cot mattresses: results from a pilot study.
AB - AIM: To assess the prevalence of plastic wrapping of cot mattresses and their
thickness. METHODS: Mothers of infants less than six months attending Plunket
clinics in Central Auckland were interviewed. The thickness of the plastic was
measured. RESULTS: 99 of 110 (90%) mothers invited to participate were visited at
home. The sample was socioeconomically advantaged. Most infants were breastfed
and few slept prone. The prevalence of plastic wrapped cot mattresses was 23.2%,
of which sixteen (out of 23) used BabeSafe and seven used other types. The mean
thickness of the BabeSafe was 0.15 mm (range 0.12-0.19 mm) and the other types
were 0.10 mm (range 0.04-0.13 mm). One sample of plastic was 0.04 mm. CONCLUSION:
Thin plastic wrapping is being used and is potentially dangerous.
PMID- 11008608
TI - A decade of intensive care unit trauma admissions in Auckland.
AB - AIMS: To describe the demographics, nature and severity of injury of trauma
admissions to a New Zealand urban Intensive Care Unit (ICU) over a ten year
period; to determine differences in injury characteristics between patients
received from inside and outside the local trauma catchment area; and to
calculate incidence rates in the local population served, to identify high risk
groups of patients. METHODS: We carried out a cross-sectional analysis of a
prospective ICU patient registry. Data on all trauma admissions from 1988 to 1997
to the ICU of a large New Zealand urban hospital were studied with respect to
age, gender, ethnicity, injury type and severity, and referral status. National
Census data for the ICU catchment area were used to calculate incidence rates for
local admissions. RESULTS: A total of 2305 trauma patients were admitted over the
period of the study, accounting for 25% of all ICU admissions. The median age was
28 years and 75% were males. Blunt trauma, mostly due to motor vehicle crashes,
accounted for 95% of admissions and penetrating trauma was very rare. The median
Injury Severity Score (ISS) was 26 and most life threatening injuries occurred in
the head region. Referred admissions were more severely injured and had a higher
prevalence of severe head injury than local admissions. The ICU trauma admission
rate for local patients was 34.6 per 100,000 person-years. Males had a higher
rate than females in all age groups. New Zealand Europeans made up the majority
of admissions, but Maori and Pacific Island males had the highest incidence
rates. CONCLUSIONS: This study identified trauma as a major component of the ICU
population. ICU trauma admissions were characterised by young males with head
injuries resulting from motor vehicle crashes. Referred admissions were more
severely injured than local admissions and would thus distort the estimated
incidence of trauma in the local geographic region served. Calculation of
incidence rates highlighted a significantly higher risk of ICU trauma admission
amongst Maori and Pacific Islands people than New Zealand Europeans.
PMID- 11008609
TI - Risk assessment in upper gastrointestinal haemorrhage: implications for resource
utilisation.
AB - AIMS: Acute upper gastrointestinal (GI) bleeding is a common and serious problem
with an associated mortality of some 10%. It is desirable, both for optimising
outcomes and for the efficient use of resources, that some form of risk
assessment be made early and management be stratified accordingly. A risk scoring
system was recently proposed and validated by Rockall and colleagues from the UK.
We wished to assess its validity in a New Zealand setting. METHODS: 565
consecutive patients treated for acute upper gastrointestinal bleeding at
Wellington Hospital between 1988 and 1991 were the subject of a major prospective
study. All patients were retrospectively assigned a score of 0-7 based on
presentation criteria as suggested by Rockall and colleagues. The score is a
composite one having regard to age, haemodynamic variables on presentation and
associated serious co-morbidity. Correlation was sought between the score and the
in hospital mortality risk. RESULTS: The overall 30-day mortality was 11%. Of the
60.5% of patients with a total score of less than 4 ('low risk'), the group
mortality was 3.2%. Of the 39.5% of patients with a total score of 4-7 ('high
risk'), the group mortality was 22.4%. CONCLUSIONS: The scoring system appears as
valid in a New Zealand patient population as in the UK. We suggest that this
scoring system be adopted in hospitals for patients with acute upper GI bleeding
to efficiently direct the use of 'intensive care' type facilities to those most
at risk, and thereby optimise management.
PMID- 11008610
TI - Posterior urethral valves: failure of antenatal diagnosis.
PMID- 11008611
TI - Work capacity evaluation.
PMID- 11008612
TI - Inhaled steroids for chronic obstructive pulmonary disease--where are we now?
PMID- 11008613
TI - Market testing the testers: lessons from recent New Zealand clinical laboratory
management strategy.
PMID- 11008614
TI - Report of the Cancer Control Workshop '99. Members of the National Cancer Control
Steering Committee.
PMID- 11008615
TI - Queensland tick typhus infection acquired whilst on holiday in Queensland.
PMID- 11008616
TI - The effectiveness of postal dissemination of evidence-based clinical guidelines.
PMID- 11008617
TI - British Toxicology Society Annual Congress. University of York, 26-28 March 2000.
Abstracts.
PMID- 11008618
TI - 31st Malaysia-Singapore Congress of Medicine. 20-24 August 1997. Abstracts.
PMID- 11008619
TI - 3rd Meeting of the Asian Society of Cardiothoracic Anesthesia and 11th ASEAN
Congress of Anesthesiologists. 7-11 July 1999. Abstracts.
PMID- 11008620
TI - International Conference in Gastroenterology. 23-25 July 1999. Abstracts.
PMID- 11008621
TI - Annual meeting of the Canadian Society for Clinical Investigation, The Royal
College of Physicians and Surgeons of Canada, and participating societies.
Edmonton, Alberta, Canada. September 21-24, 2000. Abstracts.
PMID- 11008622
TI - 36th Annual meeting of the European Association for the Study of Diabetes.
Jerusalem, Israel, 17-21 September 2000. Abstracts.
PMID- 11008623
TI - 15th Annual meeting of the European Society of Human Reproduction and Embryology
and annual meeting of the French Federation for the Study of Reproduction. Tours,
France, 26-30 June 1999. Abstracts.
PMID- 11008624
TI - 22nd Annual meeting of the American Society for Bone and Mineral Research.
Toronto, Ontario, Canada. September 22-26, 2000. Abstracts.
PMID- 11008625
TI - VIII International Conference on Inborn Errors of Metabolism. Cambridge, United
Kingdom, 13-17 September 2000. Abstracts.
PMID- 11008626
TI - Psychoanalysis at the millennium.
AB - This article explains and discusses the immense complexity of the psychoanalytic
process as it is becoming increasingly understood at the millennium, and offers
the possibility that it can be viewed from at least five channels of
psychoanalytic listening. The careful ongoing examination of the transference
countertransference interactions or enactments, and their "analytic third" (32)
location in the transitional space is extremely important in psychoanalytic
practice. We must be careful in our interpretations of the clinical data not to
stray any farther from the fundamental concepts of Freud than is necessary, lest
we end up with a set of conflicting speculative metaphysical systems and become a
marginalized esoteric cult. Freud's work remains our basic paradigm, the core of
psychoanalysis, even though his papers on technique and his emphasis on the
curative power of interpretation are from a one-person psychology standpoint and
his view of psychoanalysis as just another empirical 19th-century science
requires proper understanding and emendation in the light of accumulated clinical
experience since his time.
PMID- 11008627
TI - Cognitive therapy of schizophrenia: a new therapy for the new millennium.
AB - Over the past decade, major advances have been made in extending the principles
and therapeutic strategies of cognitive therapy to the treatment of
schizophrenia. In a number of large-scale outcome studies with cognitive therapy
for schizophrenia, cognitive therapy has been shown to offer significant gains
for those patients who have not been wholly helped with medications. It may even
serve to prevent the consolidation of the illness if delivered with those in the
early stage of the illness. We first outline the "state-of-the-art"
conceptualization and strategies employed by cognitive therapists to treat
positive and negative symptoms and then review the clinical trials.
PMID- 11008628
TI - Preserving the "psychosocial" in an era of biological psychiatry.
AB - For psychodynamic thinking and understanding to feel relevant to psychiatric
residents in current training programs, it must focus on the clinical problems
they encounter with patients. It must be presented in everyday language and in a
form applicable to their own clinical experience. Abstract theory or "deep"
formulation may alienate rather than attract interest.
PMID- 11008629
TI - The application of computerized content analysis of natural language in
psychotherapy research now and in the future.
AB - For many years the author and his colleagues have been involved in studying the
roots and processes of the conveyance of semantic messages via spoken language
and verbal texts. After establishing that reliable and valid measurements of
highly relevant neuropsychiatric categories, such as anxiety, depression, and
cognitive impairment, can be made by identifying and counting the occurrence per
grammatical clause of language content and form categories typifying specific
content-analysis scales, the research focus has turned towards computerizing this
process of content analysis. This report summarizes the achievements and
applications of the current empirical status of this method of computerized
content analysis of natural language to psychotherapy research, and it speculates
on possible future applications in the millennium.
PMID- 11008630
TI - New trends for a new millennium.
AB - Six new trends leading us into the new millennium are described. They include
psychotherapy integration, specialization, managing care, the expanding scope of
practice, cultural diversity, and psychotherapy without walls. We are entering an
age of greater public access to psychotherapeutic interventions, and more control
of our professional field. Changes will be revolutionary.
PMID- 11008631
TI - Object relations and intersubjectivity in depression.
AB - Starting with a clinical vignette the authors discuss Freud's thesis from
"Mourning and Melancholia" (1917) that depression is a defense against the
experience of loss: Whilst a part of the self remains identified with the lost
object another part directs all the aggression against it that originally had
been directed against the object. As a result the relationship between self and
object becomes replaced by a pathological relationship between parts of the self.
As psychoanalytical and phenomenological-hermeneutical approaches congruently
show, one reason why mourning cannot proceed and feelings of guilt cannot be
worked through lies in the fact that depressive patients need a symbiotic,
idealizing type of identification with their objects in order to stabilize their
identity. Because of their narcissistic vulnerability changes, personal failures,
and disappointment by their objects, which may provoke unconscious aggression and
fear of loss, can easily threaten their psychic equilibrium. This gives rise to
considerable difficulties within the transference-countertransference
relationship. The authors argue that to establish a feeling of autonomy in
depressive patients, a secure framework within therapy has to be offered and at
the same time the negative transference must thoroughly be worked through.
PMID- 11008632
TI - Neurological dysfunction, psychic conflict, and psychotherapy.
AB - Clinical experience of psychotherapists is getting more and more circumscribed by
the boundaries of theoretical references. The Freudian "psychic treatment" for
neurosis got its impetus from the friendship between Sigmund Freud and Ludwig
Binswanger, the phenomenological psychiatrist. This relationship laid the
foundation for the references of psychoanalytic psychotherapy in Europe. Then,
the Freudian conception of actual neurosis led to a psychosomatic approach.
Later, the study of narcissistic neurosis opened up to borderline patients.
Today, scientific and medical progress greatly influence psychopathological
research and the way we look at our patients and their requests. These changes
come from the patients' sayings and their expectancy of well-being. At the same
time psychotherapists have to take a new look at their theoretical references. On
the one hand, a dynamic concept for psychotherapy is necessary for integrating
the phenomenologic approach into psychoanalysis, and providing the understanding
of situations emerging in neurological dysfunction. On the other hand,
psychotherapists pay more attention to the different actors contributing to a
pathology (Who is suffering? What about the life-partner or the relatives?).
These changes lead to a new look into the processes of identification as well as
the notion of identity. This article discusses these influences on psychotherapy
and clinical research showing how clinical situations get ahead of theoretical
references.
PMID- 11008633
TI - Presentness: an intersubjective dimension of the therapeutic act.
AB - In this article, the author discusses a mode of the therapist's presence as an
important dimension within the intersubjective framework. She seeks to introduce
the term presentness to denote dimensions of the therapist's explicit usage of
her implicit knowledge and the role of her unformulated experiences within the
therapeutic situation. The emphasis is on the power of these shared states of
mutual reverie and moments of spontaneous responsiveness on the part of the
therapist. The author wants to emphasize again that this term describes an
important, though not exclusive, dimension of the therapeutic interaction. It
does not replace such psychic functions as observation, distancing, empathy, or
such modes of object-relating as transference, countertransference or projective
identification. The term presentness illuminates the symmetrical dimension of the
therapeutic interaction, and its contribution to the construction of
"meaningfulness" for both patient and therapist.
PMID- 11008634
TI - The birth of reality: psychoanalytic developmental considerations.
AB - In this article, utilizing an emended version of Winnicott's notion of
transitional objects and recent parent-infant research, the author offers a
perspective on the development of individuals' experience of being alive and real
in relation to objects and persons. Primary transitional objects, which represent
parent-infant interactions, facilitate the infant's transition from early
undifferentiated, bodily, and global experiences of being real and alive to the
infant's yoking and extending these subjective organizations to recognized not-me
objects. Secondary transitional objects make their appearance when the child
begins to acquire the capacities for self-reflexivity, symbolization, and
language. These objects provide the child with opportunities to gain confidence
and courage in extending, yoking, and making use of his/her subjective
experiences of being alive and real in relation to cultural symbols and rituals.
More importantly, secondary transitional objects are paths toward mutual
recognition, acceptance, and sharing experiences of being alive and real.
PMID- 11008635
TI - Second generation to Holocaust survivors: enhanced differentiation of trauma
transmission.
AB - "Second generation to Holocaust Survivors" is a description of a segment of
society, as well as an attempt at characterizing these individuals. It is common
to speak of mechanisms of transmission of trauma as characterizing the dynamics
of the second generation. This paper intends to advance differentiation between
two kinds of transmission of trauma: direct transmission (also called
transposition) and indirect transmission. There seems to be some confusion in
this realm, since there is some discrepancy between clinical and the experimental
publications: Whereas the first usually presents evidence of direct transmission
of trauma in the second generation, the second mostly demonstrates indirect
transmission. We shall present a clinical account of group therapy demonstrating
indirect transmission, proposing a distinction between second-generation
individuals owing to the relative dominance of each of the mechanisms in their
mental structuring. This distinction has significant clinical consequences.
PMID- 11008636
TI - Psychotherapy with older adults.
AB - The scope of need and possible benefit of psychosocial interventions in late life
far exceeds the scientific evidence of efficacy. Most studies have been conducted
in academic settings with self-selected, relatively independent older adults for
whom measures of benefit were narrowly defined. In reviewing the existing
literature concerning individual, group, and couples therapies in the geriatric
population, we find that with appropriate adaptations for medical comorbidity,
cognitive and sensory impairment, caregiver inclusion, and realistic modification
of treatment goals, psychotherapeutic endeavors with the senior patient can prove
to be highly successful.
PMID- 11008637
TI - Transpersonal psychotherapy.
AB - The history, theory, and practice of Transpersonal (or Spiritual) Psychotherapy
are presented. The author describes his own evolution from a traditional
psychoanalyst to a psychotherapist who uses the tools and wisdom from spiritual
traditions to enhance traditional psychotherapy while, at the same time,
improving the self system of the therapist. Dangers as well as benefits of the
spiritual approach are outlined. The creation and holding of a spiritual or
transpersonal context is described and ways to ascertain, in the clinical
situation, the appropriateness of such an approach are explained. The use of
bibliotherapy to help transform and expand the worldview of the patient is
outlined. Prayer and meditational systems also have a healing role in this
approach. To illustrate the uses of Transpersonal Psychotherapy in practice, four
cases are presented: 1) a paranoid schizophrenic man, 2) a well-functioning
borderline person, 3) a very poorly functioning borderline person, and 4) a high
functioning neurotic man who had been in psychoanalysis.
PMID- 11008638
TI - Narrative lessons for the psychotherapist: Kafka's the metamorphosis.
PMID- 11008639
TI - [Periodate oxidation in chemistry of nucleic acid. Dialdehyde derivatives of
nucleosides, nucleotides, and oligonucleotides].
AB - The employment of periodate oxidation in the chemistry of nucleic acids and their
components is reviewed. The reaction mechanism, structural requirements to
substrates, and synthesis of dialdehyde derivatives of nucleosides, nucleotides,
and oligonucleotides are discussed in the first part. The second part involves
chemical, physicochemical, and biological properties of the dialdehyde
derivatives, as well as their use for the affinity modifications of proteins.
PMID- 11008640
TI - [Biologically active fragment of the differentiation factor from HL-60 cell line.
Identification and properties].
AB - Six-membered peptide fragment TGENHR (HLDF-6) was identified in the HL-60 cell
culture of human promyelocyte leukemia treated with retinoic acid when studying
the differentiation factor HLDF of this cell line. HLDF-6 retains the ability of
the full-size factor to induce the differentiation and arrest the proliferation
of the starting HL-60 cells. It was shown that the synthetic peptide HLDF-6 has
no specific receptors on the surface of the HL-60 cells but can affect the
binding of interleukin IL-1 beta, a cytokine involved in proliferation, to the
cell surface. It was found on a model of transplantable NSO myeloma that HLDF-6
has an antitumor activity.
PMID- 11008641
TI - [Solid phase catalytic hydrogen isotope exchange in dalargin].
AB - A [3H]Dalargin preparation with a molar radioactivity of 52 Ci/mmol was obtained
by the high temperature solid-state catalytic isotope exchange (HSCIE) of tritium
for hydrogen at 150 degrees C. This tritium-labeled peptide was shown to
completely retain its biological activity in the test of binding to opioid
receptors from rat brain. The dissociation constant of the Dalargin-opioid
receptor complex was found to be 4.3 nM. The dependencies of the chemical yield
and the molar radioactivity on the reaction time and temperature of HSCIE were
determined. The activation energy of the HSCIE reaction for the peptide was
calculated to be 32 kcal/mol. The amino acid analysis showed that tritium is
distributed between all the amino acid residues of [3H]Dalargin at the HSCIE
reaction, with the temperature growth significantly increasing the total tritium
incorporation and, especially, enhancing the radioactivity incorporation into
aromatic residues.
PMID- 11008642
TI - [Analytical biotechnology of recombinant peptides and proteins. II. Primary
structure of the fusion protein containing human proinsulin and optimization of
its proteolysis by trypsin].
AB - The kinetics of trypsin proteolysis of the fusion protein (FP) containing human
proinsulin was studied by a set of analytical micromethods. These were the
microcolumn reversed-phase HPLC and the qualitative identification by MALDI-TOF
mass spectrometry and amino acid sequencing. The first stage of the proteolysis
was shown to be the cleavage of FP into the leader fragment and proinsulin. The
subsequent splitting off of C-peptide from proinsulin results in the formation of
ArgB31-ArgB32-insulin. The effect of temperature on the formation of de-ThrB30
insulin, a by-product, was also studied. The structure of FP was confirmed by the
peptide mapping technique, and the leader fragment was shown to contain no N
terminal Met residue.
PMID- 11008643
TI - [Hydrolysis of chimeric proteins by enteropeptidase at the specific linker
(Asp)4Lys depending on refolding conditions].
AB - Refolding from inclusion bodies of chimeric proteins containing the
enteropeptidase-specific linker (Asp)4Lys was carried out. It was shown that,
depending on the refolding conditions, chimeric proteins function as substrates
or inhibitors of the enteropeptidase. The efficiency of the enteropeptidase
hydrolysis of chimeric proteins containing the (Asp)4Lys linker may depend not
only on the amino acid sequence of the protein binding site for the enzyme but
also on the site conformation.
PMID- 11008644
TI - [Coupling of proteolysis with ATP hydrolysis by Escherichia coli Lon proteinase.
I. Kinetic aspects of ATP hydrolysis].
AB - Some aspects of the ATPase function of the Escherichia coli Lon protease were
studied around the optimum pH value. It was revealed that, in the absence of the
protein substrate, the maximum ATPase activity of the enzyme is observed at an
equimolar ratio of ATP and Mg2+ ions in the area of their millimolar
concentrations. Free components of the substrate complex (ATP-Mg)2- inhibit the
enzyme ATPase activity. It is hypothesized that the effector activity of free
Mg2+ ions is caused by the formation of the "ADP-Mg-form" of the ATPase centers.
It was shown that the activation of ATP hydrolysis in the presence of the protein
substrate is accompanied by an increase in the affinity of the (ATP-Mg)2- complex
to the enzyme, by the elimination of the inhibiting action of free Mg2+ ions
without altering the efficiency of catalysis of ATP hydrolysis (based on the kcat
value), and by a change in the type of inhibition of ATP hydrolysis by the (ADP
Mg)- complex (without changing the Ki value). Interaction of the Lon protease
protein substrate with the enzyme area located outside the peptide hydrolase
center was demonstrated by a direct experiment.
PMID- 11008645
TI - [Isotyping of human C4 complement using differences in the functional activity of
C4A and C4B isotypes].
AB - The difference in the functional activity of the isotypes A and B of component C4
of human complement was used to determine their ratio and to detect the inherited
deficiency of the isotypes. ELISA methods were developed for the quantitative
assay of component C4 (conventional sandwich method) and its functional activity.
When determining the functional activity, the classic pathway of the complement
and therefore of component C4 was activated by activators sorbed on ELISA
microplates (immunoglobulin IgG3 or liposaccharide of the Shigella sonnei cell
walls, which activates the complement by binding component C1). The nascent
fragment C4b is covalently bound to the target activator; C4Ab binds better to
the target protein (immunoglobulin), and C4Bb to the target carbohydrate
(liposaccharide). Therefore, when immunoglobulin is a target activator, isotype
C4A is bound and determined; and when the complement is activated by
liposaccharide, isotype C4B is determined. The ratio of the activities determined
by the two methods indicates a deficiency in the individual isotypes of component
C4 or its absence. The rabbit polyclonal monospecific antibodies against the
human component C4 and the conjugates of these antibodies with horseradish
peroxidase were used in the methods described.
PMID- 11008646
TI - [Turbidimetric study of latex agglutination in 2,4-dichlorophenoxyacetic acid
analysis].
AB - By the example of 2,4-dichlorophenoxyacetic acid (2,4-D) assay by the inhibition
of latex agglutination, new synthetic polymer microspheres for the conjugation
with antibodies to 2,4-D and agglutinators based on ovalbumin and polyacrylamide
were developed and characterized. The effect of various parameters (the
concentration of reagents, the type and the degree of modification of the
microsphere surface, and the nature of the carrier in the composition of the
agglutinator) on the rate of agglutination and the maximal optical absorption
observed during the reaction were studied by turbidimetry. The optimal parameters
were found for the assay of 2,4-D by the inhibition of latex agglutination with
turbidimetric registration of the results.
PMID- 11008648
TI - Social networks and the elderly: conceptual and clinical issues, and a family
consultation.
AB - After a general introduction to the construct "social networks," this article
discusses the progressive transformation of the personal social network--family,
friends and acquaintances, work and leisure relationships, et cetera--as
individuals reach an advanced age. This is followed by a summary and discussion
of a clinical consultation, with an emphasis on the reciprocal influence between
individual and social network.
PMID- 11008649
TI - Tales full of sound and fury: a cultural approach to family therapeutic work and
research in rural Scandinavia.
AB - The concept of "culture" figured prominently in the development of family
therapy. Recent conceptualizations, however, have tended to focus primarily on
the ideational dimensions of culture. While not disputing that meanings and other
ideas constitute significant features of group lifeways, this article proposes a
return to earlier anthropological framings that incorporate material and
ideational dimensions of cultures. To illustrate how his expanded concept may
serve as a guide for therapeutic work, the article describes therapy with one
family at a clinic in rural Scandinavia. We especially focus on the place of key
symbols as historical links between the ideational and material dimensions of
cultures. The perspective developed here is one of seeing cultures as sets of
interpenetrating actions and ideas shaped by as well as shaping their
practitioners.
PMID- 11008650
TI - The deconstruction of magic: rereading, rethinking Erickson.
AB - This article examines the case history writings of Milton Erickson as literary
texts. A deconstructive analysis reveals that the modernist assumption of
therapist as magical healer disguises the role clients play in their own change.
Hypothetically constructed case transcripts contrasted with excerpts from
Erickson (see Rossi, 1980) illustrate how the inclusion of client voice enriches
understanding of therapeutic change.
PMID- 11008651
TI - Evolving the biobehavioral family model: the fit of attachment.
AB - The 1993 Biobehavioral Family model (BBFM) posits that family relational patterns
and biobehavioral reactivity interact so as to influence the physical and
psychological health of the children. The revised 1999 BBFM incorporates parent
child attachment as a pivotal construct. The current study tests the 1999 BBFM by
predicting, in asthmatic children, that child perception of parental relationship
quality, triangulation of child in marital conflict, and parent-child security of
relatedness will be associated with hopelessness and vagal activation (one
mechanism of airway compromise in asthma). In this study, 22 children with asthma
(11 males/11 females, aged 8 to 16), watched, alone, an emotionally challenging
movie, then engaged in family discussion tasks (problem solving, loss, conflict,
cohesion) and completed the Children's Perception of Interparental Scale, the
Relatedness Questionnaire, The Multidimensional Scale of Anxiety in Children, and
the Hopelessness Scale for Children. Heart rate variability, measured at baseline
and throughout the movie and family tasks, was used to compute respiratory sinus
arrhythmia (RSA)--an inferential measure of vagal activation. The child's
perception of parental conflict showed trends of association with triangulation
and insecure father-child relatedness. Triangulation and hopelessness also were
associated with insecure father-child relatedness, all of which were associated
with vagal activation. Insecure mother-child relatedness was correlated only with
hopelessness. Anxiety was not related to any variables. These findings lend
support to the 1999 BBFM, and suggest a key role for parent-child attachment.
PMID- 11008652
TI - Empathy in families of women with borderline personality disorder, anorexia
nervosa, and a control group.
AB - This is a study of empathy in the families of 27 women with borderline
personality disorder (BPD), 28 women with restricting anorexia nervosa (AN), and
27 women without a clinical diagnosis (NC). The daughters and both parents
responded to the Interpersonal Reactivity Index (IRI), an instrument for
assessing four dimensions of empathy. In addition, they were personally
interviewed, with the Family Interview for Protectiveness and Empathy (FIPE),
about the extent of empathy expressed by the parents to their daughter during her
development. On the IRI, women with BPD scored highest on the immature and lowest
on the mature aspects of empathy, whereas scores of AN and NC women were all
within normal limits. Parents of BPDs had the lowest IRI scores, while parents of
AN and NC groups were similar to each other and to criterion group scores. IRI
scores of AN daughters were positively correlated with their parents' scores
whereas BPDs' scores were negatively correlated with those of their parents.
There were no correlations between the IRI scores of NC subjects and their
parents. On the FIPE, borderline daughters and parents agreed about the relative
absence of empathic parenting, whereas AN and NC daughters and parents agreed as
to the presence of empathic parenting. The theoretical and clinical implications
of these contrasting findings are discussed.
PMID- 11008653
TI - Family perception of interpersonal behavior as a predictor in eating disorders: a
prospective, six-year followup study.
AB - This study assessed family perception patterns of interpersonal behavior in
families with a daughter diagnosed with an eating disorder 6 years after
treatment that used a prospective design. Family perception patterns of patients
found to have a poor outcome at followup (n = 15) were compared with patients
with a good outcome (n = 23), as well as a control group (n = 36). Using the
system of multiple level observation of groups (SYMLOG), all 238 family members
evaluated themselves and each other. The index patients with a poor outcome
perceived themselves as friendlier and more positive than they were perceived by
their families. In comparison to parents of daughters with a good outcome and the
control group, parents of daughters in the poor outcome group perceived
themselves to be less friendly than their partners perceived them to be. A rigid
polarization of the perception of the index patient by family members and a
discrepancy in this perception between the index patient and the rest of the
family were found to be indicative of a poor prognosis. Implications for
treatment based on family perception patterns of interpersonal behavior are
discussed.
PMID- 11008654
TI - Further evidence that the family assessment device should be reorganized:
response to Miller and colleagues.
AB - Ridenour, Daley, and Reich's (1999) factor analyses of the Family Assessment
Device (FAD) indicated that the FAD be reorganized. Miller and colleagues (2000)
contend that the FAD be used in its original format based on the FAD's
theoretical foundation; however, this does not preclude the importance of
scientific scrutiny of an instrument's construct validity to determine how well
an instrument represents its theoretical base. Subscale factor analyses
(exploratory and confirmatory), item-level factor analysis, and the clinical and
psychometric studies cited by Miller and colleagues suggest a more parsimonious
FAD configuration and were consistent with Ridenour and colleagues' factor
analyses.
PMID- 11008655
TI - Why fix what isn't broken? A rejoinder to Ridenour, Daley, & Reich.
AB - Ridenour, Daley, & Reich (2000) suggest that the Family Assessment Device should
be reorganized. We disagree and provide further reasons why such a reorganization
is unwise.
PMID- 11008656
TI - M. leprae-HIV co-infection: pattern of immune response in vivo and in vitro.
PMID- 11008657
TI - The source of infection: an unsolved issue.
PMID- 11008658
TI - Cytokine patterns using molecular tools.
PMID- 11008659
TI - Prospects for chemotherapy of leprosy.
PMID- 11008660
TI - Clinical leprosy through the last seventy-five years.
PMID- 11008661
TI - An epidemiological analysis of leprosy from 1951-1996 in Sichuan.
AB - Through the leprosy surveillance system established in 1990s the authors analysed
the epidemiology of leprosy in Sichuan province from 1951 to 1996. By the end of
1996, the total number of registered cases was 32,772, the peak incidence rate
(2.44/100,000) was in 1958. The annual average progressively decreasing speed
(AAPDS) of the number of new cases, incidence rate, incidence rate among
children, number of newly detected patients, detection rate, number of registered
cases and registered prevalence rates were 4.7% (xg = 0.9534), 5.9% (xg =
0.9407), 7.4% (xg = 0.9263), 6.7% (xg = 0.9326), 8.1% (xg = 0.9195), 10.9% (xg =
0.8913) and 11.7% (xg = 0.8828) respectively. Among newly detected cases, the
proportion of children gradually declined with an AAPDS of 2.9% (xg = 0.9712),
but that of household contacts gradually increased, showing a gradual decline of
source of infection. The multibacillary (MB) rate among new cases, newly
registered cases and active cases also increased gradually. The MB rate among
child cases was much lower than that among adults. The disability rates among
newly registered cases tended to decline. The peak incidence was in the 20 to 35
years age group, the average age at onset being 31.92 years. Average age at onset
gradually increased to 34.19 during 1991-1995. The average interval between onset
of symptoms and diagnosis was 4.89 years and that had reduced gradually to 3.24
years during 1991-1995. The authors conclude that: (1) the epidemiological trend
of leprosy in Sichuan province shows decline; (2) the case-finding activities
have improved and intensified; but (3) the disability rate among newly detected
cases is still high (> 20%) and the average delay in diagnosis is still too long,
showing that early case finding is still not satisfactory.
PMID- 11008662
TI - Techniques for covering soft tissue defects resulting from plantar ulcers in
leprosy: Part V. Use of the flap in the inguinal region and latissimus dorsi
musculocutaneous flap.
AB - The area of distribution of the superficial circumflex iliac, superficial
epigastric and superficial external pudental arteries is large and flaps based on
them can meet the requirement of different recipient sites. We have transplanted
free flaps based on the superficial epigastric artery for repairing plantar soft
tissue defects in six leprosy patients. During the follow-up examination 58 to
118 months later there has been no recurrence of ulceration in any of these
cases. The latissimus dorsi muscle, is mainly nourished by the thoracadorsal
artery and the latissimus dorsi musculocutaneous flap is a large sized, composite
structure with abundant blood provision and strong anti-infectious property. The
latissimus dorsi flap can be used as an artery-pedicled island flap or as a free
flap besides its use as a muscle graft, because of its constant vascular
position, wide outer-diameter of the vessels and long pedicle. It can therefore
be utilized for repairing soft tissue defect or replacement of paralyzed muscle.
We have used the latissimus dorsi musculocutaneous free flap for repairing large
skin and soft tissue defects resulting from plantar ulceration in three leprosy
patients. During the follow-up period, one patient who had complete drop-foot and
had refused corrective surgery had recurrence of the ulcer in the 12th post
operative month. No ulcers had recurred in the other two cases during the follow
up at 48 and 114 months.
PMID- 11008663
TI - Leprosy presenting as macrocheilia.
PMID- 11008664
TI - Modification of the "wrap around" tendon anastomosis of fascia lata graft with a
slim double tendon of palmaris longus.
PMID- 11008665
TI - Chemotherapy in paucibacillary leprosy.
PMID- 11008666
TI - Leprosy patients and their spouses.
PMID- 11008668
TI - Alternative strategy to total population survey.
PMID- 11008667
TI - Community based leprosy survey in U.T. Chandigarh.
PMID- 11008669
TI - Elimination of leprosy--what should it mean and what should we do: a personal
view.
PMID- 11008670
TI - Where's the line?
PMID- 11008672
TI - Improving mental health professional-client relationships.
PMID- 11008671
TI - Storytelling: using an ancient art to work with groups.
PMID- 11008673
TI - Resiliency is key for children to overcome adversity.
PMID- 11008674
TI - Fall incidence in a state psychiatric hospital in Singapore.
AB - The results of a retrospective study of fall incidence during a 1-year period in
a psychiatric hospital in Singapore are reported, involving 309 patients who fell
one or more times during their stay. The profile of inpatients involved in falls
was identified. Data were derived from standard incident forms completed whenever
patients had a fall. A total of 348 falls were identified for the 1-year period.
Results revealed higher fall rates in younger male epileptic patients; elderly
female patients, age 70 and older with depression or dementia; individuals with
concomitant medical conditions; and patients taking three types of medication.
The majority of falls occurred when the activity level was high in the ward.
Young epileptic patients and elderly depressed patients were prone to repeated
falls. These results have the potential to assist in identifying patients at high
risk and in designing and implementing strategies to prevent such incidents.
PMID- 11008675
TI - Facilitating a multidisciplinary parent support & education group guided by
Allen's developmental health nursing model.
AB - Parents are generally the primary source of support and nurturing for children
experiencing an eating disorder; yet, they often feel blamed for the illness.
Guided by the developmental health model, the group focused on parents'
competence and helped them share solutions; reframed situations related to
development in adolescence and mid-life; and shifted the emphasis to process to
help parents understand behaviors. Parents became partners in helping their
children recover by sharing solutions and creating learning opportunities from
adversity.
PMID- 11008676
TI - The history, economics, and financing of mental health care. Part 1: 17th to 19th
centuries.
AB - Families in colonial times cared for their mentally ill members at home, with
little assistance from their communities. Community treatment is an old idea, not
a new one. Early laws about containing the disturbances created by individuals
with mental illness made no mention of clinical dimensions. The focus was
strictly on the social and economic consequences of the mental disorders.
Legislation about public mental hospitals in the mid-19th century was hardly
enlightened. There were no particular plans, other than not to expend more
dollars than actually necessary.
PMID- 11008678
TI - What psychiatric nurses should teach the public above mental health?
PMID- 11008677
TI - Combined group process-psychoeducation model for psychiatric clients and their
families.
PMID- 11008679
TI - [Structure and function of microbial communities in soil from the southern
Taiga].
AB - General regularities in the structure of the microbial communities of southern
taiga soil ecosystems and taxonomic differences between the microbial communities
of soils with different hydrothermal characteristics are discussed with reference
to the main types of soils of the Central State Forest Biosphere Reserve.
PMID- 11008680
TI - [Synthesis of osmoprotectors by halophilic and alkalophilic methanotrophs].
AB - The 1H-NMR analysis of methanol extracts of halophilic and halotolerant
alkaliphilic methanotrophs isolated from the soda lakes of Southern Transbaikal
and Tuva showed that bacterial cells grown at an optimum salinity accumulated
mainly sucrose and 5-oxo-1-proline, whereas cells adapted to 0.5-1.0 M NaCl
additionally synthesized ectoine. A more detailed study showed that nitrogen
deficiency in the growth medium of Methylobacter alcaliphilus 20Z decreased the
synthesis of nitrogen-containing osmoprotectants, ectoine and 5-oxo-1-proline. M.
alcaliphilus 20Z cells exhibited activities of UDP-glucose pyrophosphorylase and
sucrose-phosphate synthase involved in sucrose synthesis. Glutamine synthetase in
vitro did not require NH4+ ions, which implies that this enzyme is involved in 5
oxo-1-proline synthesis. Cells grown at high salinity exhibited elevated levels
of aspartate kinase, aspartate-semialdehyde dehydrogenase, and ectoine synthase.
This suggests that ectoine is synthesized via aspartate and aspartate
semialdehyde, i.e., via the route earlier established for extremely halophilic
bacteria.
PMID- 11008681
TI - [Manganese-dependent ribonucleotide reductase of Propionibacterium freudenreichii
subsp. shermanii: partial purification, characterization, and role in DNA
biosynthesis].
AB - Like Lactobacillus leichmanii, Rhizobium meliloti, and Euglena gracilis, P.
freudenreichii implicates cobalamin in DNA anabolism via adenosylcobalamin
dependent ribonucleotide reductase. However, in the absence of corrinoids, P.
freudenreichii is able to synthesize DNA with the involvement of an alternative
ribonucleotide reductase, which is independent of adenosylcobalamin. This enzyme
is localized in both the cytoplasm (80% of activity) and the cytoplasmic membrane
(20% of activity), being loosely bound to the latter. Experiments with crude
ribonucleotide reductase isolated from extracts of corrinoid-deficient cells
showed that manganese specifically stimulates this enzyme and that it is composed
of two protein subunits, a feature that is typical of all metal-containing
reductases activated by molecular oxygen. Low concentrations of manganese ions
enhanced DNA synthesis in corrinoid-deficient manganese-limited cells. This
effect was prevented by the addition of 80 mM hydroxyurea, a specific inhibitor
of metal-containing aerobic ribonucleotide reductases. It was concluded that, in
adenosylcobalamin-deficient P. freudenreichii cells, DNA synthesis is provided
with deoxyribosyl precursors through the functioning of manganese-dependent
aerobic ribonucleotide reductase composed of two subunits.
PMID- 11008682
TI - [Dependence of the effect of RNAase from Bacillus intermedius on the growth of
baker's yeast on the concentration of the exogenous enzyme].
AB - Bacillus intermedius RNase added at a low concentration (0.001 microgram/ml)
stimulated yeast growth, while a high RNase concentration (1500 micrograms/ml)
was inhibitory to yeast growth. The inhibitory effect of RNase was transient and
correlated with the increase in the trehalose pool of yeast cells. The number of
unbudded cells in the yeast population tended to decrease under the action of low
concentrations of bacillar RNase and to increase under the action of high
concentrations of this enzyme.
PMID- 11008683
TI - [Destruction of chlorinated derivatives of phenol: ortho-chlorophenol, para
chlorophenol, and 2,4-dichlorophenoxyacetic acid by bacteria communities in
anaerobic sludge].
AB - The bacterial community of anaerobic sludge could degrade ortho-chlorophenol,
para-chlorophenol, and 2,4-dichlorophenoxyacetic acid at concentrations as high
as 100 mg/l. The time needed for the degradation of a given chlorinated phenol
derivative increased 1.5- to 2-fold upon a twofold increase in its concentration
(from 50 to 100 mg/l). The duration of the adaptation period depended on the
compound studied and on its concentration. The degradation of 2,4
dichlorophenoxyacetic acid proceeded via 2,4-dichlorophenol and p-chlorophenol as
intermediates; the degradation of o-chlorophenol occurred with the formation of
phenol. The dynamics of p-chlorophenol degradation and chloride ion accumulation
were studied.
PMID- 11008684
TI - [Growth of Rhodococcus opacus on mixtures of monohalogenated benzenes and
phenols].
AB - The growth of Rhodococcus opacus GM-14 on mixtures of 2-chloro- and 2
bromophenol, of 4-chloro, 4-bromo-, and 4-iodophenol, and of chloro-, bromo-, and
iodobenzenes was accompanied by consumption of the substrates and excretion of
halogen ions to the medium. During the growth on monochlorophenols, the
substrates were consumed sequentially in the following order: 4-chloro-, 3-chloro
, and then 2-chlorophenol. Chlorine ions were excreted in a two-phase manner in
amounts comprising 79% of the theoretical yield. The diauxic growth of R. opacus
GM-14 can be explained by the existence in this bacterium of two modified
metabolic pathways for the ortho-cleavage of halogenated pyrocatechols. The first
pathway included 4-halogeno- or dihalogenopyrocatechols as intermediates, whereas
the second pathway included 3-halogenopyrocatechols.
PMID- 11008685
TI - [Preparation and characteristics of mutant strains of Penicillium funiculosum-
producers of glucose oxidase].
AB - After the mutagenesis of Penicillium funiculosum with UV light and N-nitroso-N
methylurea, 83 of 2237 grown colonies were surrounded with increased zones of
glucose oxidase diffusion. Analysis of the glucose oxidase activity of selected
mutant strains grown in submerged cultures allowed 18 mutant strains to be
obtained whose glucose oxidase activity was 5-153% higher (in a medium with
glucose) and 4-83% higher (in a medium with sucrose) than that of the parent
strain. Two of these mutant strains, UV6.31 and NMU95-132, possessed high glucose
oxidase activity when grown in media with glucose or sucrose and produced large
amounts of mycelia. The active and morphologically stable mutant P. funiculosum
NMU95-132 was chosen for further selection work.
PMID- 11008686
TI - [Inorganic polyphosphates and phosphohydrolases from Halobacterium salinarium].
AB - Halobacterium salinarium grown in a liquid medium consumed up to 75% of
phosphates originally present in the growth medium and accumulated up to 100
mumol Pi/g wet biomass by the time it entered the growth retardation phase. The
content of acid-soluble oligophosphates in the biomass was maximum at the early
stage of active growth and drastically decreased when cells reached the growth
retardation phase. The total content of alkali-soluble and acid-insoluble
polyphosphates changed very little throughout the cultivation period (five days).
The polyphosphate content of H. salinarium cells was close to that of yeasts and
eubacteria. The pyrophosphatase, polyphosphatase, and nonspecific phosphatase
activities of H. salinarium cells were several times lower than those of the
majority of eubacteria. The specific activity of pyrophosphatase, the most active
hydrolase of H. salinarium, gradually increased during cultivation, reaching 540
mU/mg protein by the end of the cultivation period. Half of the total
pyrophosphatase activity of this halobacterium was localized in the cytosol. The
molecular weight of pyrophosphatase, evaluated by gel filtration, was 86 kDa. The
effective Km of this enzyme with respect to pyrophosphate was 115 microM.
PMID- 11008687
TI - [Features of phospholipid composition of marine proteobacteria of
Pseudoalteromonas species].
AB - The study of the phospholipid composition of 14 type strains of marine
proteobacteria of the genus Pseudoalteromonas showed that phospholipids are the
main polar lipid constituents of membranes in these proteobacteria. The
phospholipid patterns of the strains studied were found to be similar and
involved five phospholipids typical of gram-negative bacteria, namely,
phosphatidylethanolamine, phosphatidylglycerol, bisphosphatidic acid,
lysophosphatidylethanolamine, and phosphatidic acid. The major phospholipids were
phosphatidylethanolamine and phosphatidylglycerol, which add up to 89-97% of
total phospholipids; bisphosphatidic acid was dominant among minor phospholipids.
The prevalence of phosphatidylethanolamine (62-77% of total phospholipids) and
the absence of diphosphatidylglycerol are the characteristic features of most
bacteria of this genus. As in Escherichia coli, the phospholipid composition of
the marine proteobacteria depended on the presence of magnesium in the medium.
PMID- 11008688
TI - [Changes in the carbohydrate composition of cytosol from fungal spores in
connection with environmental temperature and during storage].
AB - Differences in the carbohydrate composition were revealed among spores of fungi
belonging to Zygomycetes, Ascomycota, Basidiomycota, and Oomycota, part of the
novel kingdom Chromista. It was shown for the first time that Phytophthora
infestans contains arabitol in addition to glucose and trehalose. Sucrose was
detected in Pleurotus ostreatus basidiospores. It was established that Blakeslea
trispora stylospores contain inositol. The dependence of the spore carbohydrate
composition on the temperature of the habitat of the corresponding species is
discussed. It was shown that the cytosol of the conidia is dominated by trehalose
and inositol under hypothermic conditions and by mannitol and glucose under
hyperthermic conditions. Neomycota and Eomycota were shown to differ in their
responses to stress (starvation), which correlated with the differences in the
carbohydrate composition of the spore cytosols. Assuming that cytosol
carbohydrates perform a protective function, we explain the higher viability of
conidia compared to stylo- and sporangiospores.
PMID- 11008689
TI - [Effect of nitrogen sources on biosynthesis, chemical composition, and structure
of exopolysaccharides from Aureobasidium pullulans (de Bary) Arnaud].
AB - The effect of the nitrogen source and the C/N ratio of the growth medium on the
biosynthesis, composition, and structure of the exopolysaccharides (EPSs) of
Aurebasidium pullulans (de Bary) Arnaud var. aubasidani Yurlova var. nov. and A.
pullulans var. pullulans was studied. A. pullulans var. pullulans and A.
pullulans var. aubasidani strains synthesized the maximum amounts of EPSs in the
presence of, respectively, a reduced nitrogen source ((NH4)2SO4) and an oxidized
nitrogen source (NaNO3) in the medium. The data presented confirm the validity of
using the chemical composition and structure of the major cetavlon-precipitated
fraction of A. pullulans EPSs for the characterization of intraspecies taxa.
PMID- 11008690
TI - [Microbiological processes at the interface of aerobic and anaerobic waters in
the deep-water zone of the Black Sea].
AB - Chemical and key microbiological processes (assimilation of carbon dioxide,
oxidation and formation of methane, and sulfate reduction) occurring at the
boundary between the aerobic-anaerobic interface in the deep-water zone of the
Black Sea were investigated. Measurements were taken at depths from 90 to 300 m
at intervals of 5-10 m. The integral rate of the dark assimilation of carbon
dioxide varied from 120 to 207 mg C/(m2 day) with a maximum at the boundary of
cyclonic currents. The organic matter (OM) formed from methane comprised less
than 5% of the OM formed from carbon dioxide. A comparison between the rates of
methane oxidation and methane production suggests that methane that is oxidized
at depths from 100 to 300 m was formed in deeper water horizons. The maximum rate
of sulfate reduction (1230 mg S/(m2 day)) was observed in the western halistatic
region, and the minimum rate (490 mg S/(m2 day)), in the eastern halistatic
region. The average rate of hydrogen sulfide production measured at three deep
sea stations amounted to 755 mg S/(m2 day), or 276 g S/(m2 year).
PMID- 11008691
TI - [Effect of microorganisms and seasonal factors on the isotope composition of
organic carbon from Black Sea suspensions].
AB - The isotopic composition of particulate organic carbon (POC) from the Black Sea
deep-water zone was studied during a Russian-Swiss expedition in May 1998. POC
from the upper part of the hydrogen sulfide zone (the C-layer) was found to be
considerably enriched with the 12C isotope, as compared to the POC of the
oxycline and anaerobic zone. In the C-layer waters, the concurrent presence of
dissolved oxygen and hydrogen sulfide and an increased rate of dark CO2 fixation
were recorded, suggesting that the change in the POC isotopic composition occurs
at the expense of newly formed isotopically light organic matter of the biomass
of autotrophic bacteria involved in the sulfur cycle. In the anaerobic waters
below the C-layer, the organic matter of the biomass of autotrophs is consumed by
the community of heterotrophic microorganisms; this results in weighting of the
POC isotopic composition. Analysis of the data obtained and data available in the
literature allows an inference to be made about the considerable seasonable
variability of the POC delta 13C value, which depends on the ratio of terrigenic
and planktonogenic components in the particulate organic matter.
PMID- 11008692
TI - [Potential activity of methane and ammonia oxidation by methanotropic communities
from soda lakes of the southern Transbaikal].
AB - Radioisotopic measurements of the methane consumption by mud samples taken from
nine Southern Transbaikal soda lakes (pH 9.5-10.6) showed an intense oxidation of
methane in the muds of lakes Khuzhirta, Bumalai Nur, Gorbunka, and Suduntuiskii
Torom, with the maximum oxidation rate in the mud of lakes Khuzhirta (33.2
nmol/(ml day)). The incorporation rate of the radioactive label from 14CH4 into
14CO2 was higher than into acid-stable metabolites. Optimum pH values for methane
oxidation in water samples were 7-8, whereas mud samples exhibited two peaks of
methane oxidation activity (at pH 8.15-9.4 and 5.8-7.0). The majority of samples
could oxidize ammonium to nitrites; the oxidation was inhibited by methane. The
PCR amplification analysis of samples revealed the presence of genes encoding
soluble and particulate methane monooxygenase and methanol dehydrogenase. Three
alkaliphilic methanotrophic bacteria of morphotype I were isolated from mud
samples in pure cultures, one of which, B5, was able to oxidize ammonium to
nitrites at pH 7-11. The data obtained suggest that methanotrophs are widely
spread in the soda lakes of Southern Transbaikal, where they actively oxidize
methane and ammonium.
PMID- 11008693
TI - [Characteristics of bacterioplankton in the Loess-containing Lake Khanka].
AB - Some characteristics of bacterioplankton--generation time, daily (P) and specific
(P/B) bacterioplankton production, and bacterial metabolic coefficient K2--in the
loess-containing Lake Khanka were determined using five modifications of the
bacterial-count procedure with the fluorescent dyes fluorescamin and erythrosin.
Experiments showed that the organomineral complex (OMC) in this lake is broken
down by chemoorganoheterotrophic bacteria. The increase in the loess content of
the lake water intensified bacterial growth and the cycles of potassium, silicon,
and other biogenic elements. The addition of starch to a loess suspension
activated the breakdown of OMC due to the adsorption of starch on the OMC/water
interface and stimulation of the metabolism of attached bacteria.
PMID- 11008694
TI - [Spatial integration of partners and heteromorphism of cyanobacterium Nostoc
muscoum CALU 304 in mixed culture with Rauwolfia].
AB - A comparative morphological study was conducted of Nostoc muscorum CALU 304 grown
either as a pure culture on standard media or as a mixed culture with Rauwolfia
callus tissue on a medium for plant tissue cultivation. The interaction of the
cyanobacterial and plant partners results in their spatial integration into
aggregates of specific anatomy, which arise periodically during the mixed culture
growth. The morphology of the cyanobacterial cells varies depending on their
localization in the combined aggregate. The degree of cyanobacterial
heteromorphism increases with time of growth of the association. Evidence of the
plant origin of the factors inducing heteromorphic changes in N. muscorum was
obtained, as well as evidence indicating that these factors can rapidly diffuse
in agarized medium. A conclusion is inferred that the heteromorphic cells
correspond to bacterial forms that appear during unbalanced growth as an
adaptation to altered environmental conditions.
PMID- 11008695
TI - [Microbiological database UNIQEM: problems and prospects].
AB - The UNIQEM database, designed to accumulate microbiological data of a general
nature, is currently used to store and make available information about
microorganisms studied and maintained at the Institute of Microbiology, Russian
Academy of Sciences. UNIQEM is composed of two related databases. The first one
is a catalogue database, used to accumulate and maintain list-form information on
a wide range of microorganisms. The second one is a property database, which
facilitates collecting, processing, and publishing diverse data having to do with
these microorganisms and their properties. The database supports the retrieval of
microorganisms by specifying an arbitrary set of their properties and has the
potential for eventually evolving into a computer instrument for unattended
identification of microorganisms.
PMID- 11008696
TI - [Microsampling of rhizosphere soil and laboratory artefacts].
AB - A parallel analysis of the microsamples of surrounding soil and microsamples of
rhizosphere soil did not reveal the so-called rhizospheric effect. The data
obtained showed that dilution significantly influences the results of
determination of the number of soil microorganisms. The actual number of
microorganisms revealed in soil samples greatly differed from the theoretically
predicted values. The enumeration of microorganisms in soil microsamples by
direct count and, especially, by the plating method with the use of conversion
coefficients based on the degree of sample dilution gave erroneous results.
PMID- 11008697
TI - [Glucuronate media for isolating tremelloid yeasts].
AB - D-Glucuronate-containing agar is suggested for evaluation the population density
and diversity of tremelloid yeasts in natural cenoses. This medium is superior to
the commonly used wort agar on which many representatives of tremelloid yeasts
cannot be revealed.
PMID- 11008698
TI - Endocrine disruptors: present issues, future directions.
AB - A variety of natural products and synthetic chemicals, known collectively as
endocrine-disrupting compounds (EDCs), mimic or interfere with the mechanisms
that govern vertebrate reproductive development and function. At present,
research has focused on (i) the morphological and functional consequences of
EDCs; (ii) identifying and determining the relative potencies of synthetic and
steroidal compounds that have endocrine-disrupting effects; (iii) the mechanism
of action of EDCs at the molecular level; and (iv) the recognition that in "real
life," contamination usually reflects mixtures of EDCs. Future research must
examine (i) the interactive nature of EDCs, particularly whether the threshold
concept as developed in traditional toxicological research applies to these
chemicals; (ii) when and how EDCs act at the physiological level, particularly
how they may organize the neural substrates of reproductive physiology and
behavior; (iii) the various effects these compounds have on different species,
individuals, and even tissues; and (iv) how adaptations may evolve in natural
populations with continued exposure to EDCs. Several predictions are offered that
reflect these new perspectives. Specifically, (i) the threshold assumption will
be found not to apply to EDCs because they mimic the actions of endogenous
molecules (e.g., estrogen) critical to development; hence, the threshold is
automatically exceeded with exposure. (ii) Behavior can compound and magnify the
effects of EDCs over successive generations; that is, bioaccumulated EDCs
inherited from the mother not only influence the morphological and physiological
development of the offspring but also the offsprings' reproductive behavior as
adults. This adult behavior, in turn, can have further consequences on the sexual
development of their own young. (iii) The sensitivity of a species or an
individual to a compound is related to species (individual)-typical
concentrations of circulating gonadal steroid hormones. Related to this is the
recent finding that alternate forms of the putative receptors are differentially
distributed, thereby contributing to the different effects that have been
observed. (iv) Except in extraordinary situations, populations often continue to
exist in contaminated sites. One possible explanation for this observation that
needs to be considered is that animals can rapidly adapt to the nature and level
of contamination in their environment. It is unlikely that successive generations
coincidentally become insensitive to gonadal steroid hormones fundamentally
important as biological regulators of development and reproduction. Rather,
adaptive alterations in the genes that encode steroid receptors may occur with
chronic exposure to EDCs, allowing the sex hormone receptor to discriminate
natural steroids from EDCs.
PMID- 11008699
TI - Kin selection and parasite evolution: higher and lower virulence with hard and
soft selection.
AB - Conventional models predict that low genetic relatedness among parasites that
coinfect the same host leads to the evolution of high parasite virulence. Such
models assume adaptive responses to hard selection only. We show that if soft
selection is allowed to operate, low relatedness leads instead to the evolution
of low virulence. With both hard and soft selection, low relatedness increases
the conflict among coinfecting parasites. Although parasites can only respond to
hard selection by evolving higher virulence and overexploiting their host, they
can respond to soft selection by evolving other adaptations, such as
interference, that prevent overexploitation. Because interference can entail a
cost, the host may actually be underexploited, and virulence will decrease as a
result of soft selection. Our analysis also shows that responses to soft
selection can have a much stronger effect than responses to hard selection. After
hard selection has raised virulence to a level that is an evolutionarily stable
strategy, the population, as expected, cannot be invaded by more virulent
phenotypes that respond only to hard selection. The population remains
susceptible to invasion by a less virulent phenotype that responds to soft
selection, however. Thus, hard and soft selection are not just alternatives.
Rather, soft selection is expected to prevail and often thwart the evolution of
virulence in parasites. We review evidence from several parasite systems and find
support for soft selection. Most of the examples involve interference mechanisms
that indirectly prevent the evolution of higher virulence. We recognize that hard
selection for virulence is more difficult to document, but we take our results to
suggest that a kin selection model with soft selection may have general
applicability.
PMID- 11008700
TI - The diversity of parasites.
AB - Parasitism is one of the most successful modes of life displayed by living
organisms, as measured by how often it evolved and how many parasitic species are
presently in existence. Studying the diversity of parasites is particularly
relevant because sympatric diversification may be important in some parasite
taxa, and because of the opportunity for independent tests of evolutionary
hypotheses in the many separate lineages in which parasitism evolved. Our
incomplete knowledge of existing parasite species--the result of a range of
phenomena that includes inadequate sampling effort or the lumping of different
cryptic species under one name--is not always a major obstacle for the study of
parasite diversity. Patterns in the diversity of parasites may be associated with
either host or parasite characteristics. The distribution of parasite diversity
among host taxa does not simply reflect the species diversity of the host taxa
themselves; life history and ecological traits of hosts appear to play important
roles. These may determine the likelihood that hosts are colonized by parasite
species over evolutionary time. It is not yet clear whether some host traits also
favor intrahost speciation and diversification of parasites, and the formation of
new parasite species. Certain features of parasites may also be associated with
speciation and diversification. Only parasite body size has received much
attention; the patterns observed are not greatly different from those of free
living species, with small-bodied parasite taxa being more speciose than related
large-bodied taxa. Epidemiological parameters such as the basic reproductive rate
of parasites, or R0, can also generate predictions regarding the distribution or
evolution of parasite diversity. For instance, parasite taxa characterized by
high R0 values may be more speciose than related taxa with lower values of R0;
such predictions remain untested. Large-scale biogeographical patterns of
diversity have only been well studied for metazoan parasites of marine fish; for
these parasites, latitudinal patterns can be explained by effects of temperature
on speciation rates and epidemiological variables, though other causes are
possible. The emphasis for future research must shift from pattern description to
the elucidation of the processes responsible for the structure and diversity of
parasite faunas. A better integration of ecological and historical (or
phylogenetic) approaches to the study of parasite diversity should make this
objective possible.
PMID- 11008701
TI - Rapid diagnosis of pseudorabies virus infection in swine tissues using the
polymerase chain reaction (PCR).
AB - In Argentina pseudorabies is an endemic disease. Routine diagnosis is made by
virus isolation. It is a very long procedure to carry out and gives variable
results depending on the quality of sample, hence the need for effective
techniques, which are rapid and not dependent on the isolation of infectious
virus. The polymerase chain reaction (PCR) technique has provided a sensitive,
specific and rapid mean to detect DNA sequences. This study describes a PCR
method for detection of pseudorabies virus sequences in swine tissues. In order
to determine the presence of suid herpesvirus-1 DNA and antigens, 36 tissue
samples collected from 19 dead pigs, with signs of pseudorabies infection, were
examined by PCR, virus isolation and indirect immunofluorescence, respectively.
Fifteen out of 19 pigs were positive at least for one tissue by PCR (15/19) while
only three pseudorabies virus strains were isolated (3/19). All the amplified
products were identified by digestion with Sa/l and hybridization. The method
described herein circumvents tedious viral isolation and DNA purification and
would be a valuable tool for rapid diagnosis, since it would take less than 5 h
to reach an accurate result even in poorly preserved tissue samples.
PMID- 11008702
TI - [In vitro infection by different strains of Paracoccidioides brasiliensis].
AB - We analyzed the in vitro infection process by P. brasiliensis and the effect of
extracellular factor(s) produced on monolayers of mammalian Vero cell lines. The
yeast phase of four strains was studied: B339 (avirulent or slightly virulent),
U, (intermediate virulence), 93745 and 63265 (both highly virulent). Strains of
intermediate and high virulence had higher adherence at first contact (about
16%). Strain B339 had a slower adherence at first contact (8%) than the others
during the same period. The production of extracellular proteases, soluble
extracellular factor(s) and extracellular antigen gP43 showed no correlation with
the in vitro physiopathogenicity of the analyzed strains. We demonstrate that the
Vero model presented in this paper is a suitable system to study infection and
virulence in vitro. We are currently assessing its usefulness as a tool for the
analysis of the interaction between pathogen, host and antifungal agents.
PMID- 11008703
TI - Criteria for Candida albicans numerical analysis based on electrophoretic protein
patterns.
AB - Even in normalized gels, some problems with the choice and position of protein
bands always have hindered the processing of electrophoretic data. We have
developed a way to establish which criterion best fits the necessities in order
to maximize the similarity indexes for numerical analysis. Some repetitions of a
Candida albicans strain were carried out in eleven different gels. After
staining, the bands were scored in numbers within ranges of +/- n values with
increases of one quarter steps (+/- 0.25 kDa, +/- 0.5 kDa, +/- 0.75 kDa, +/- 1.0
kDa, +/- 1.25 kDa) that will limit the possibility of variation for the same
bands that will appear on the repetitions. Using this criterion, we have
determined that values scored within +/- 1.25 kDa could optimize the minimum
limiting value of similarity in different dendrograms built.
PMID- 11008704
TI - [Mucocutaneous leishmaniasis in naturally infected dogs in Salta, Argentina].
AB - The objective of the present study is to describe two cases of dogs with
mucocutaneous lesions caused by Leishmania spp. Both dogs presented destruction
of the nasal septum, hyperemia with soft palate edema and barking alteration due
to laryngeal compromise. Biopsies were taken from the lesion border and
Leishmania spp. amastigotes were seen in the imprints. The dogs presented
positive serology when complex soluble antigen from Leishmania mexicana was used.
One of the dogs was also suspected to be infected by Trypanosoma cruzi as
suggested by its positive reaction with a purified specific antigen, Ag163B6
cruzipain. Most of the studies concerning leishmaniosis in dogs have described
the cutaneous form of this disease in close association with human cases of
Leishmania infection instead of the mucocutaneous form described herein. The
presence of dogs with mucocutaneous leishmaniosis alerts on an increase of the
prevalence of this form in humans, which can cause deforming lesions, alterations
of the speech and even an inadequate nutrition due to difficulties in
deglutition.
PMID- 11008706
TI - [Comparison of 2 techniques for the laboratory diagnosis of influenza virus
infections].
AB - The clinical or epidemiological influenza diagnosis require fast, sensitive and
accessible techniques for small laboratories. In order to investigate the
sensitivity of the methods currently used in Argentina, the rapid diagnosis by
indirect immunofluorescent assay (IF) was compared to the rapid viral culture in
MDCK cells. The diagnosis of influenza virus infection was performed on 81 nasal
and pharyngeal swabs collected from outpatients with upper respiratory infection,
influenza-like syndrome. The samples were collected during 1998 winter season and
both techniques were tested. The IF specificity and sensitivity obtained were
91.9% and 59.5%, respectively. In the selection of the assay to be used for
influenza diagnosis, the limitations of the simplest techniques such as IF should
be considered. Furthermore, it is advisable to set up an optimized culture method
in complex laboratories since culture is the only technique which allows the
reference centers to perform the full characterization of the isolates.
PMID- 11008705
TI - Inactivation of Trypanosoma cruzi dihydrolipoamide dehydrogenase by leukocyte
myeloperoxidase systems: role of hypochloride and nitrite related radicals.
AB - Dihydrolipoamide dehydrogenase (LADH) from Trypanosoma cruzi, the causative agent
of Chagas' disease, was inactivated by treatment with myeloperoxidase (MPO)
dependent systems. LADH lipoamide reductase and diaphorase activities decreased
as a function of incubation time and composition of the MPO/H2O2/halide system, a
transient increase preceding the loss of diaphorase activity. Iodide, bromide,
thiocyanide and chloride were effective components of MPO/H2O2 or MPO/NADH
systems. Catalase prevented LADH inactivation by the MPO/NADH/halide systems in
agreement with H2O2 production by NADH-supplemented LADH. Thiol compounds (L
cysteine, N-acetylcysteine, penicillamine, N-(2-mercaptopropionylglycine) and
Captopril prevented LADH inactivation by the MPO/H2O2/NaCl system and by NaOCl,
thus supporting HOCl as agent of the MPO/H2O2/NaCl system. MPO/H2O2/NaNO2 and
MPO/NADH/NaNO2 inactivated LADH, the reaction being prevented by MPO inhibitors
and thiol compounds. T. cruzi LADH was affected by MPO-dependent systems like
myocardial LADH, allowance being made for the variation of the diaphorase
activity and the greater sensitivity of the T. cruzi enzyme to MPO/H2O2/halide
systems.
PMID- 11008707
TI - [Blood cultures: use of presumptive antiobiograms].
AB - Mortality associated to bacteremia varies between 20 and 40% depending upon
several factors, such as focus of infection, microorganism, host conditions, etc.
It has also been documented that mortality may double when the patient does not
receive antibiotic treatment to which the microorganism is susceptible. The
objective of our work has been to determine the correlation between disk
diffusion antibiogram according to NCCLS guidelines, from isolated colonies, and
the one performed directly from the blood culture flask. During 1996, in the
Institute of Cardiology and Cardiovascular Surgery (ICYCC) in Buenos Aires City,
81 episodes of bacteremia were studied. In every case, an antibiogram was carried
out: 1) from the bottle: a- Directly (D), harvesting 20 microliters in Mueller
Hinton agar, b- Diluted (d), previous centrifugation and Gram staining to adjust
turbidity equivalent to 0.5 Mc Farland; 2) from isolated colonies, according to
NCCLS guidelines. There were almost no major errors, except with two strains of
Enterobacter cloacae versus cephalotin. The diluted method was not so convenient
to read inhibition zones, especially with staphylococci. With gram-positive
bacteria, the main problems appeared in the direct method with erythromycin,
oxacillin and ciprofloxacin because of minor errors. With gram-negative bacteria,
major errors were observed in the direct method, mainly with piperacillin (7%)
and to a lesser extent with piperacillin tazobactam (2%). Except for imipenem,
trimethoprim sulfamethoxazoie and cefotaxime, all antimicrobial agents presented
minor errors with both methodologies. Based upon the high rate of minor errors,
we consider it is important to confirm results obtained with the standard
technique (NCCLS), considering as presumptive those results from the blood
culture bottles (D and d).
PMID- 11008708
TI - [Thermophilic endospores in the environment of a sugar mill in Jujuy].
AB - Twenty six samples from green and scorched sugarcane stems and leaves, sugarmill
air dust and raw sugar were analyzed. Thirty nine thermophilic bacilli strains
were isolated. Physiological and morphological examinations were carried out
according to Bergey's Manual. The strains were identified as B. licheniformis
(66.7%), B. coagulans (17.9%), B. stearothermophilus (10.3%) y B. subtilis
(5.1%).
PMID- 11008709
TI - [Relationship between rhodamine 6G accumulation and fluconazole resistance in
Saccharomyces cerevisiae S288c].
AB - Severe mycotic infections are a source of concern in immunocompromised patients
or in those who receive chemotherapy for hematological malignant diseases. One of
the causes is referred to the appearance of antimycotic resistant microorganisms.
Fluconazole is one of the antimycotic used for invasive mycoses treatment.
Therefore it is necessary to evaluate the factors that originate this resistance.
In the present report the yeast Saccharomyces cerevisiae S288c was used as a
model system. In resistant strains the accumulation of the lipophilic cation
Rhodamine 6G, L-leucine uptake and growth inhibition by crystal violet dye were
determined. The results presented herein demonstrate the correlation between the
membrane potential and the resistance to fluconazole presented by S. cerevisiae
strain S288c.
PMID- 11008711
TI - Membership directory 2000-2001 of the Missouri State Medical Association.
PMID- 11008710
TI - [Isolation of Escherichia coli O157:H7 in storm drains in the city of Mar del
Plata with bacterial contamination of fecal origin].
AB - The present study was focused on the isolation and characterization of
Escherichia coli, particularly the serotype O157:H7, from five combined-sewer
outflows waters, which drain into the beaches of Mar del Plata. Seventeen
hemolytic uremic syndrome cases were reported in Mar del Plata during the
sampling period (May 1995-April 1996) in children between 9 month- and 5 year
old, and 3 deaths were recorded. E. coli identification was carried out by
biochemical tests. E. coli was detected in 75% of the samples and a total of 98
strains were selected, with 11 sorbol non-fermenting strains. The strains
belonged to the O1, O6, O44, O86a, O119 and O168 serogroups. As none of the known
virulence factors was detected, strains could not be grouped within any of the
diarrheagenic E. coli categories. None of the E. coli strains belonged to the
O157:H7 serotype, but E. coli isolation showed fecal contamination in the
combined-sewer outflows. Since their waters drain into beaches for recreational
use, it is necessary to emphasize the detection of E. coli that would cause
severe human illness. Bacterial pollution in combined-sewer outflows draining
into Mar del Plata coasts might represent a high risk for human health.
PMID- 11008712
TI - [98th Meeting of the German Ophthalmology Society. 21-24 September 2000, Berlin,
Germany. Abstracts].
PMID- 11008713
TI - Index 1921-1999.
PMID- 11008714
TI - Pennsylvania Medical Society 2000-2001 membership directory.
PMID- 11008715
TI - 5th Italian Association of Nuclear Medicine (AIMN) Congress. Pesaro, June 17-20,
2000. Abstracts.
PMID- 11008716
TI - [XXVII National Congress of the Spanish Society of Digestive Pathology. La
Coruna, 17-20 June 2000. Abstracts].
PMID- 11008717
TI - Microsatellite instability in colorectal adenomas: relevance and clinical
importance.
AB - A number of investigations have recently been published on the role of
microsatellite instability (MSI) in the process of colorectal carcinogenesis. The
data concerning colorectal adenomas are difficult to compare (due to differences
in the tumor collection, selection and number of analyzed loci, definition of
high and low instability and histological types), and this review therefore
examines the significance of the results of these publications. We then discuss
the extent to which MSI and its effects on the integrity of the genome are early
or late events in the malignant transformation, and which clinicopathological
features are presented by MSI-positive adenomas. Finally, we consider the
clinical importance of microsatellite status for the diagnosis of hereditary
nonpolyposis colorectal cancer and the possibility of preventing adenomas and
carcinomas by nonsteroidal anti-inflammatory drugs.
PMID- 11008718
TI - Increase in the immunostimulatory effect of dendritic cells by pulsing with serum
derived from pancreatic and colorectal cancer patients.
AB - Both we and others have observed a relative resistance of solid tumor cells to
immunological effector cells in vitro, which may be one reason for the clinical
phenomenon of resistance of patients with pancreatic carcinoma or other solid
tumors to immunological therapeutic approaches. Dendritic cells (DC) are
professional antigen-presenting cells which can process and present tumor
associated antigens such as CA 19-9. Here we tested DC pulsed with serum
containing CA 19-9 for their capacity to stimulate immunological effector cells
against pancreatic carcinoma cells. Coculture of immunological effector cells
with DC led to a significant increase in cytotoxic activity as measured by a
lactic dehydrogenase release assay. Most interestingly, cytotoxic activity
against tumor cells was further increased using DC pulsed with patient-derived CA
19-9 containing serum. Similar results have been obtained using either autologous
or allogeneic serum from patients with pancreas carcinoma. The effect of serum on
the cytotoxicity of effector cells increased in a dose-dependent manner.
Interestingly, heat inactivation led to a significant loss of immunostimulatory
capacity of the serum. Cytotoxicity was partially inhibited by using an antibody
directed against CA 19-9 on the surface of the target cells. Best results were
obtained when adding CA 19-9 protein to CA 19-9 containing serum for pulsing of
DC. In conclusion, DC pulsed with CA 19-9 containing serum increased the
cytotoxic activity of immunological effector cells against pancreatic cancer
cells. DC pulsed with CA 19-9 containing serum with or without additional
exogenous CA 19-9 protein may have an impact on immunotherapeutic protocols for
patients with CA 19-9 secreting tumors.
PMID- 11008719
TI - Frequently relapsing Crohn's disease is characterized by persistent elevation in
interleukin-6 and soluble interleukin-2 receptor serum levels during remission.
AB - We examined immune and inflammatory activation during remission in patients with
Crohn's disease who presented with various clinical profiles (prolonged remission
vs. relapsing disease). Thirty-six patients with at least 3 years' follow-up
starting from a remission period were studied retrospectively. Relapses were
defined by a retrospective calculation of the Crohn's disease activity index or
by the clinical judgement of the physicians in charge of the patients. Disease
course over the study period was assessed by the mean number of annual relapses.
Analysis used measurements during remission of the following: erythrocytes
sedimentation rate, relative lymphocytosis, acid alpha1-glycoprotein, interleukin
6 (IL-6), and soluble interleukin-2 receptor (sIL-2R) serum levels. During the
study period 21 patients experienced at least one relapse and 15 did not. Mean
serum levels of sIL-2R and mean relative lymphocytosis in remission significantly
discriminated between relapsing and nonrelapsing patients. Only the mean sIL-2R
serum level was selected by multivariate analysis, with a cutoff value of 82 pM/1
(sensitivity of 76% and specificity of 80%). The only features correlated with
mean number of annual relapses in the relapsing patients were mean serum levels
of sIL-2R (r=0.58, P=0.015) and IL-6 in remission (r=0.45, P=0.039). Multivariate
analysis demonstrated statistical significance only for the mean serum level of
IL-6 (P=0.014). In Crohn's disease the persistent elevation in sIL-2R serum
levels during remission corresponds to chronic active disease, while high serum
levels of IL-6 in these patients is associated with a high frequency of relapse.
PMID- 11008720
TI - Enterovesical fistulas complicating Crohn's disease: clinicopathological features
and management.
AB - Enterovesical fistula is a relatively rare condition in Crohn's disease. This
study was undertaken to examine clinicopathological features and management of
enterovesical fistula complicating Crohn's disease. Thirty patients with
enterovesical fistula complicating Crohn's disease, treated between 1970 and
1997, were reviewed. Urological symptoms were present in 22 patients; pneumaturia
in 18, urinary tract infection in 7, and haematuria in 2. In 5 patients clinical
symptoms were successfully managed by conservative treatment, and they required
no surgical treatment for enterovesical fistula. Twenty-five patients required
surgery. All the patients were treated by resection of diseased bowel and
pinching off the dome of the bladder. No patients required resection of the
bladder. The Foley catheter was left in situ for an average of 2 weeks after
operation. Three patients developed early postoperative complications; two bowel
anastomotic leaks, and one intra-abdominal abscess. All these complications were
associated with sepsis and multiple fistulas at the time of laparotomy. After a
median follow-up of 13 years, 3 patients having postoperative sepsis (anastomotic
leak or abscess) developed a recurrent fistula from the ileocolonic anastomosis
to the bladder, which required further surgery. In the other 22 patients without
postoperative complications there has been no fistula recurrence. In conclusion,
the majority of patients with enterovesical fistula required surgical treatment:
resection of the diseased bowel and oversewing the defect in the bladder. The
fistula recurrence was uncommon, but the presence of sepsis and multiple fistulas
at the time of laparotomy increased the incidence of postoperative complications
and fistula recurrence.
PMID- 11008721
TI - G protein levels and function as an objective measure of depression in patients
with functional bowel disorders.
AB - Heterotrimeric G proteins play a pivotal role in postreceptor information
transduction. These proteins have been implicated in the pathophysiology,
diagnosis, and treatment of mood disorders and proposed as a state-dependent
biochemical mood marker in mononuclear leukocytes. Irritable bowel syndrome (IBS)
is associated with changes in mood, affecting patients' illness perceptions and
behavior. We examined whether mononuclear leukocytes of patients with IBS have
altered G protein measures. We undertook G protein functional measurements
through agonist-enhanced [3H]Gpp(NH)p binding capacity and quantitative measures
by immunoblot analysis using anti-Galpha antibodies in mononuclear leukocytes
obtained from 19 IBS patients (Rome criteria) and 19 healthy matched subjects.
The study groups were similar in age, gender, and years of education. Mononuclear
leukocyte functions of G(s) (21.3+/-8.3%) and G(i) (22.2+/-6.7%) proteins in IBS
patients were similar to healthy subjects (24.8+/-4.7 and 25.2+/-4.0%,
respectively). The relative immunoreactivities of the G(sa) (98.9+/-10.2%) and
the G(ia) (104.2+/-11.5%) subunit proteins in mononuclear leukocytes of IBS
patients were also similar to those in healthy subjects. Two patients clinically
diagnosed as depressed were detected by the G protein assay. The results lend
objective support to the contention that major depression is not a causative
factor in IBS, nor associated with its severity. The G protein assay may provide
an objective biochemical tool for detecting depression in IBS, differentiating it
from psychological distress that is commonly diagnosed by subjective tests.
PMID- 11008722
TI - Vascular organization in the mesorectum: angiography of rectal resection
specimens.
AB - The technical advances in rectal cancer surgery are known as the total mesorectal
excision. The resection in an anatomically defined plane under direct vision and
with sharp dissection distinguishes it conventional rectal surgery. The result
must be a complete mesorectum without deep gouges. We performed specimen
angiography to confirm completeness of the removed mesorectum. Thirteen total
mesorectal excision specimens were examined by angiography after continence
preserving resection of rectal carcinoma. In 11 of the 13 cases the vascular
supply was exclusively via the superior rectal artery. In two cases with
hypoplastic left terminating branches of the superior rectal artery there was
additional perfusion via a caudally ascending vessel or via smaller vessels
connected laterally. In all specimens both arterial supply and venous outflow
were located within the mesorectal fascial sheath. There was no radio-opaque
substance leaking from the mesorectal surface in the case of a complete
mesorectal specimen. Tiny vascular branches running laterally occurred in 7 of
the 13 cases. We found no larger vascular connections branching off in the
lateral direction. The rectal blood supply comes almost exclusively through the
superior rectal vessels. Thus the fascia covering the mesorectum forms, as far as
rectal vascularization is concerned, a closed compartment. The mesorectal vessels
are enclosed in the fibrous avascular mesorectal fascia. They run close above the
fascia. In the case of an incomplete mesorectal excision the specimen angiography
shows a stain leaking from the mesorectal fascia. Our method can be used to
confirm the completeness of the removed mesorectum.
PMID- 11008723
TI - In vitro peritonitis: basic inflammatory reactions in a two-chamber coculture
model of human peritoneum.
AB - We developed an in vitro model of the peritoneum by coculturing human umbilical
vein endothelial cells (HUVEC) and human peritoneal mesothelial cells (HPMC) to
gather information on peritoneal physiology and to closer reflect the in vivo
situation in humans. HUVEC and HPMC were seeded on collagen-coated
polytetraflourethylene-insert membranes of pore size 3 microm. HUVEC were grown
on the bottom of the membrane and HMPC on the top. The confluent cells were
monitored by measuring transepithelial resistance and by confocal microscopy. The
transmigration of PMNs as an important mechanism during secondary peritonitis was
studied in this two-chamber model. PMNs were isolated by density separation.
After stimulation of HMPC with the complement factor 5 split product C5a (1
ng/ml) or tumor necrosis factor-alpha (TNF-alpha; 10 or 50 microg/ml) for 1 h, 1
x 10(6) PMN were given to the lower compartment. Controls were cocultured cells
without stimulation. After 1, 2, and 6 h nonadherent PMNs in the upper
compartment were harvested and counted, interleukin-8 was measured in each
compartment, and cells on the membrane were paraffin-embedded for
immunohistochemistry. Each experiment was performed four times. Cells grew to
confluence within 2-5 days and were detected on their respective seeding side by
CD34 and cytokeratin 18 counterstaining. Transmigration of PMNs after C5a or TNF
alpha stimulation showed a significant time-dependent increase between 1 h and 6
h (P<0.05). PMNs were found in significantly higher numbers after stimulation
with either C5a or TNF-alpha at 1, 2, and 6 h than without stimulation. After
stimulation of HPMC, interleukin-8 secretion to the apical compartment increased
in a time-dependent fashion, resulting in a gradient between the two chambers.
Linear regression analysis revealed significant correlation between transmigrated
PMN and interleukin-8 in stimulated cocultures; no correlation was found in
controls. This new in vitro peritoneum consisting of cocultured mesothelial and
endothelial cells may allow more detailed assessment of peritoneal
pathophysiology. Generation of an interleukin-8 gradient affecting the migration
of PNMs across the cocultured membrane represents a parameter which may be
addressed in further studies.
PMID- 11008724
TI - Efficiency of combined colonoscopy and computed tomography for diagnosis of
colonic actinomycosis: a retrospective evaluation of eight consecutive patients.
AB - The preoperative diagnosis of colonic actinomycosis is accurate in fewer than 20%
of patients. Colonoscopy and computed tomography (CT) findings were analyzed to
ascertain their diagnostic value and their role in determining therapeutic
modality and outcome. Before and after treatment we retrospectively evaluated
eight consecutive patients with colonic actinomycosis, all of whom were women
with a previous history of intrauterine contraceptive device use. Median follow
up period was 20 months (7-57). Localized nodules were found in all cases by
colonoscopy; half of these nodules included umbilication at the apex. The colonic
mucosa demonstrated normal to moderate inflammation as well as hyperemia and
edema. Mucosal ulceration was found in only one case. All cases showed some
degree of stenosis. These findings differ from those in other inflammatory or
neoplastic diseases of the colon. Abdominopelvic CT revealed extramural
involvement of heterogeneous lesions all cases. Contrast enhancement also
indicated severe thickening of the colonic wall (7-20 mm) with focal and dense
enhancement in six cases. Seven of eight patients required surgery for diagnostic
or therapeutic purposes. Complete resolution was determined using both
colonoscopy and CT. As more than half of these cases could have been safely
managed using an adequate antibiotic treatment, diagnostic studies indicating a
high likelihood of colonic actinomycosis should be evaluated to avoid unnecessary
surgeries carried out for diagnostic purposes. A combination of colonoscopy and
CT appears to be important for both diagnosis and management because of their
compensatory findings of mucosal and extramucosal lesions, respectively.
PMID- 11008725
TI - A randomized trial of glyceryl trinitrate ointment and nitroglycerin patch in
healing of anal fissures.
AB - Mean maximum anal resting pressure is directly related to the activity of the
smooth muscles of the internal and external sphincters and has been found to be
increased in the patients of anal fissure. It has been shown that blood flow at
the posterior midline of anoderm is inversely related to the mean maximum anal
resting pressure, and topical application of glyceryl trinitrate (GTN) ointments
is a very successful treatment. This randomized study was designed to evaluate
the relative value of a nitroglycerin patch applied at a distance from the
fissure site in healing anal fissure compared to GTN ointment and compared to
surgical treatment. Forty-two consecutive patients with chronic anal fissure of
more than 4 months' duration were randomized into two equally sized groups: those
in group A received 0.2% GTN ointment while those in group B received a 10-mg
nitroglycerin patch for 8 weeks. Patients were also asked to rate their pain
intensity on a scale of 0-10. Five patients were excluded for various reasons;
results were analyzed for the remaining 37 patients (group A, n=18; group B,
n=19). A control group C consisted of 12 patients who underwent surgical
treatment. Fissures healed completely in 12 of 18 (66.7%) patients in group A, 12
of 19 (63.2%) in group B and 11/12 (91.7%) in group C. The healing rates in
groups A and B did not differ significantly (P=0.7), nor was there a difference
between these and surgical group C (P=0.13). The local application of GTN
ointment and the nitroglycerin patch are both effective, economical, and
alternative treatment options for most patients with anal fissures.
PMID- 11008726
TI - Glyceryl trinitrate for fissures: patch or paste?
PMID- 11008727
TI - Effects of colectomy on bile composition, cholesterol saturation and cholesterol
crystal formation in humans.
AB - Total or subtotal colectomy is the surgical treatment of choice for patients with
ulcerative colitis. Recently it has been reported that colectomy may lead to
increased lithogenicity of bile, short nucleation time, cholesterol crystal
formation, and gallstone disease. We examined whether colectomy in patients with
ulcerative colitis leads to changes in bile composition that predisposes to
cholesterol crystal formation and cholesterol gallstone disease. Ten consecutive
patients who had previously undergone ileostomy and colectomy because of
ulcerative colitis were admitted for ileal pouch surgery. At operation bile was
obtained by puncture of the gallbladder. Controls were 35 patients undergoing
cholecystectomy (23 for cholesterol gallstone disease and 12 for reasons other
than gallstone disease). The gallbladder bile was analyzed for cholesterol
crystals, bile acid, and biliary lipid composition, cholesterol saturation, and
nucleation time. The colectomized patients had normal biliary lipid composition,
normal cholesterol saturation, and normal nucleation time, in contrast to
gallstone patients who displayed highly supersaturated bile with a short
nucleation time. Thus patients with ileostomy after colectomy because of
ulcerative colitis have normal cholesterol saturation and nucleation time of
bile.
PMID- 11008728
TI - Treatment of acute strangulated internal hemorrhoids by topical application of
isosorbide dinitrate ointment.
AB - Exogenous nitric oxide has been shown useful in decreasing the internal anal
sphincter tone. This study investigated the role of isosorbide dinitrate in the
treatment of patients with acute strangulated internal hemorrhoids, thereby
avoiding the risk of continence disturbances following conventional surgical
treatment. Four male patients (median age 35 years, range 30-42) with acute
strangulated hemorrhoids were treated with 1% isosorbide dinitrate. The ointment
was applied to the anoderm. This application was repeated every 3 h during
daytime for 2 weeks. Significant pain relief was achieved within 1 day, while
transient mild headache was experienced during the first 2 days. Within 1 week
the hemorrhoids became reducible. Thereafter the hemorrhoids could be treated
adequately by rubber band ligation. The alternative treatment of patients with
acute strangulation of prolapsed internal hemorrhoids is effective. This
nonsurgical, i.e., reversible reduction of sphincter tone is an attractive
alternative.
PMID- 11008729
TI - Congenital coxa vara: computed tomographic analysis of femoral retroversion and
the triangular metaphyseal fragment.
AB - Three patients with congenital coxa vara studied with two- and three-dimensional
computed tomographic (2DCT and 3DCT) methods are reported. In all cases, the
femoral retroversion was documented and subsequently corrected by proximal
femoral osteotomy. In two patients with isolated coxa vara, the physeal-femoral
neck angle was decreased as seen in slipped capital femoral epiphysis in
adolescents. Our studies suggest that the triangular metaphyseal fragment
reflects a Salter-Harris type II separation pattern through the defective femoral
neck. The epiphysis and attached triangular fragment slip from the normal
superoanterior portion of the neck in an inferior-posterior direction. The
treating surgeon should be aware of the often marked femoral retroversion
component present in severe congenital coxa vara. This knowledge allows surgical
planning for corrective osteotomies that will better normalize hip mechanics. A
combination of marked valgus and flexion with internal rotation of the distal
fragment are required to fully correct the deformity.
PMID- 11008730
TI - Classification of metaphyseal change with magnetic resonance imaging in Legg
Calve-Perthes disease.
AB - Seventy-eight patients (85 affected hips and 71 unaffected hips) with Legg-Calve
Perthes disease were included in this study to evaluate the metaphyseal change in
radiographs and magnetic resonance imaging (MRI) and to define the type of the
metaphyseal cyst according to presence or absence of the epiphyseal involvement.
The content of the metaphyseal cyst was evaluated by using T1,T2, proton, and
gadolinium-enhanced T1-weighted MRI scans. Among 85 hips, there were no changes
in 32 hips, marrow edema in 13 hips, false cyst with epiphyseal involvement in 28
hips, and true cyst without epiphyseal involvement in 12 hips. Granulation tissue
was found in the false cysts and water-rich fibrotic tissue was found in the true
cysts based on the MRI scans. The metaphyseal change in MRI scans was shown in
71% of groups 3 and 4 and in 35% of groups 1 and 2 according to the Catterall
classification, and 52% of group A, 56% of group B, and 86% of group C according
to the Herring classification. Of the 30 hips at the avascular stage, 33% showed
metaphyseal cyst in MRI scans. Of the 53 hips at the fragmentation stage, 60%
showed the metaphyseal cyst.
PMID- 11008731
TI - The effect of pediatric orthopaedic experience on interobserver and intraobserver
reliability of the herring lateral pillar classification of Perthes disease.
AB - An analysis was done of the effect of surgeons' pediatric orthopaedic experience
on the classification of Perthes disease according to the lateral pillar
classification described by Herring. Five observers with varied pediatric
orthopaedic experience reviewed anteroposterior (AP) pelvis radiographs of 33
patients in the fragmentation phase of Perthes disease and classified each case
on three separate occasions at least 24 hours apart. Frog-leg lateral-view
radiographs taken at the same time were also classified using the same criteria
based on the femoral head anterior column. Kappa statistics showed good agreement
for intra- and interobserver reliability of classification for both AP and frog
lateral radiographs. There were no statistically significant variations among the
reviewers. Twenty-four percent of the cases had a classification one grade worse
on the lateral radiograph compared to the AP view. The lateral pillar
classification provides a reproducible radiographic technique for Perthes disease
characterization independent of pediatric orthopaedic experience.
PMID- 11008732
TI - Radiographic results of proximal femoral varus osteotomy in Legg-Calve-Perthes
disease.
AB - A retrospective review of 116 Legg-Calve-Perthes patients with varus osteotomy
for Herring group B and C disease involvement was conducted. Preoperative
assessment consisting of anteroposterior pelvis and frog leg lateral radiographs
and an arthrogram was performed on all patients. Radiographic extent of disease
was classified using Herring's lateral pillar classification system. Radiographic
outcome was assessed utilizing Stulberg's classification to grade residual
deformity. Follow-up averaged 6 years 9 months (range, 3 years to 15 years 3
months). Stulberg class I and II (spherically congruent) results were obtained in
86% of patients younger than 9 years old with Herring class B disease. Patients 9
years and older with Herring class B disease had spherically congruent results in
67% of cases. Patients with Herring class C disease 9 years and older had
spherically congruent results in 30% of cases and 43% spherically congruent
results in those younger than 9 years.
PMID- 11008733
TI - Limited magnetic resonance imaging examination after surgical reduction of
developmental dysplasia of the hip.
AB - We evaluated the utility of limited magnetic resonance imaging (MRI) after
surgical reduction and spica casting for developmental dysplasia of the hip (DDH)
with respect to feasibility, time, need for sedation, and charge. Eighteen
limited MRI examinations were performed in 10 children (mean age, 9 months) with
a 1.5-T magnet. Twenty-eight dysplastic hips were imaged within 4 hours of
surgery. Mean imaging time for two sequences was approximately 3 minutes. All
examinations were interpretable, although three were degraded by motion. No child
required sedation, additional sequences, or repeat study. Two thirds of the
dysplastic hips had no proximal femoral ossification center on MRI. A reduced
charge was assigned to the examination. We conclude that using limited MRI to
confirm intraoperative reduction for DDH is feasible and desirable. The lack of
radiation or need for sedation, the reduced charge that reflects the short time
needed for imaging, and the superb visualization of nonosseous structures have
made it our preferred method to evaluate surgical reduction of DDH.
PMID- 11008734
TI - Intraoperative instability for developmental dysplasia of the hip in children 12
to 18 months of age as a guide to Salter osteotomy.
AB - There is still debate on the necessity of Salter osteotomy for developmental
dysplasia of hip (DDH) between 12 and 18 months of age. The goals of this study
were to investigate the correlating factors of intraoperative instability as a
guide to the additional Salter osteotomy and to evaluate the radiographic and
clinical results. Stability could not be achieved in 63% of 84 hips with soft
tissue releases alone. The existence of three pathologic findings (grade of
dislocation, inverted labrum, and excessive anteversion) and absence of two
surgical procedures (transverse acetabular ligament incision and iliopsoas
osteotomy) significantly correlates with instability. At follow-up, the
acetabular remodeling with or without Salter osteotomy was similar. We conclude
that the Salter osteotomy does not interfere with the acetabular remodeling and
has no major disadvantages for children at that age but can help to improve the
stability of the hip.
PMID- 11008735
TI - Preliminary traction as a single determinant of avascular necrosis in
developmental dislocation of the hip.
AB - The role of preliminary traction before closed reduction in the treatment of
developmental dysplasia of the hip has been questioned by many authors lately.
However, the studies advocating or opposing the use of this treatment modality
include several other parameters besides traction. Thus, it is unclear whether
the affection is the result of preliminary traction or concurrent variables such
as the "human position." This study aimed to put forward the effect of
preliminary traction as a single determinant of avascular necrosis. We had two
groups of patients who had developmental dislocation of the hip. The first group
consisted of 52 patients treated with preliminary traction before closed
reduction and the other group comprised 40 patients treated with closed reduction
without preliminary traction. Both groups were similar in age, gender, side,
level of dislocation, and method and duration of immobilization. Three patients
from the first group developed avascular necrosis, which was not statistically
significant. Preliminary traction did not affect the rate of avascular necrosis.
PMID- 11008736
TI - Total hip arthroplasty after childhood septic hip in patients younger than 25
years of age.
AB - Childhood septic hip should usually be treated immediately by arthrotomy and
antibiotic. Even if treated correctly, the affected hip may become osteoarthritic
and functionally disabling. Usually the literature is not in favor of total hip
arthroplasty in young patients, and the reports are on patients older than 32
years of age. We present here a unique group of very young patients with early
coxarthrosis caused by septic hip in childhood, with an average age of 19.14
years (range, 14-25) at the time of the arthroplasty. The Harris hip score
improved from a preoperative mean of 58.43 to a postoperative mean of 94.14. The
follow-up period ranged between 2 and 24 years, with an average of 8.14 years. We
conclude that total hip arthroplasty in young people with early coxarthrosis
caused by septic hip in childhood provides good functional results.
PMID- 11008737
TI - Ultrasonographic evaluation of hip morphology in osteochondrodysplasias.
AB - The developing hip in children with osteochondrodysplasias has not been well
described because of delayed ossification and limitations of conventional
radiologic techniques. Twenty-four children with various osteochondrodysplasias
were evaluated by ultrasonography. Variation in the configuration of the
acetabulum included a horizontal acetabular roof owing to delayed iliac
development and a notched acetabular roof with lateral bone deficiency. All
children had thickened acetabular cartilage except for one child with
osteogenesis imperfecta. Coxa vara was a common finding. All neonates displayed a
very small beta angle (mean, 42 degrees) because the labrum lay more vertically,
secondary to deep engagement of the femoral head in the acetabulum. Proximal
femoral ossification was delayed in most children, which allows use of
ultrasonography at a later age than is possible in the normal pediatric
population. Hip ultrasonography in children with skeletal dysplasias can aid in
early diagnosis and is useful in assessing hip morphology and development.
PMID- 11008738
TI - The genetic basis of the osteochondrodysplasias.
AB - The osteochondrodysplasias are a heterogeneous group of disorders characterized
by abnormal growth and remodeling of cartilage and bone, affecting from 2 to 4.7
per 10,000 individuals. Most osteochondrodysplasias are heritable and many have
elaborate patterns of genetic transmission. Affected individuals generally
require management by multidisciplinary teams of specialists. In this review, we
divide the osteochondrodysplasias into groups based on their genetic
relationships, including mutations in various types of collagen, fibroblast
growth factor, cartilage oligomeric matrix protein, parathyroid hormone receptor,
the diastrophic dysplasia sulfate transporter, enzymes such as steroid
sulfatases, transcription factor SOX9, and a cysteine proteinase, cathepsin K. We
describe the major osteochondrodysplasias, define their causes and clinical
manifestations, and provide the orthopaedic surgeon with an understanding of the
underlying molecular defects as well as the anatomical aspects of these
disorders.
PMID- 11008739
TI - Treatment of late-onset tibia vara using afghan percutaneous osteotomy and
orthofix external fixation.
AB - The Afghan osteotomy was combined with external fixation on 19 patients (23
extremities) with late-onset tibia vara. The average weight was 258 lb and all
patients weighed >95th percentile. The average preoperative deformity was 28.2
degrees. The average intraoperative correction was 27.6 degrees. Average healing
time was 141 days. The mean follow-up was 2.7 years. Based on radiographic
correction, at long-term follow-up, there were 15 excellent, two fair, and six
poor results. The quality of the initial correction was the only significant
variable, and it was borderline (p = 0.0587). Complications included loss of
alignment, peroneal nerve palsy, superficial pin tract infection, deep infection,
and fracture. This method offers a technically simple procedure with a relatively
low complication rate. It allows early mobilization and provides the ability to
manipulate the correction postoperatively. An excellent long-term outcome is
predicated on achieving an acceptable initial correction as determined by
intraoperative mechanical axis radiographs.
PMID- 11008740
TI - Early characteristic findings in bowleg deformities: evaluation using magnetic
resonance imaging.
AB - We used magnetic resonance imaging (MRI) to evaluate bowleg deformities in
infancy. Twenty-five tibiae of 13 infants were examined and divided into two
groups based on MRI findings: group A had high intensity area in the medial
epiphyseal cartilage on T2-weighted images. Group B had depression of medial
physis and abnormal signal in the perichondrial region in addition to the
epiphyseal lesion. At the final follow-up, all cases in group A demonstrated
normal lower leg alignments, whereas five cases in group B showed characteristic
roentogenographic findings of Blount's disease. The improvement rate of
metaphyseal-diaphyseal angle was correlated with this classification. These
findings suggested that abnormal findings in physis and perichondrial region
might be preliminary findings in early stage of Blount's disease. The high
intensity areas in the medial epiphyseal cartilage were commonly found among the
cases with bowing deformities, which suggested that there might be a common
pathomechanism between physiologic bowing and infantile Blount's disease.
PMID- 11008741
TI - Tibial hemimelia of a different class.
AB - A variant of tibial hemimelia, previously undescribed in the literature and not
classifiable by either of the established classification systems, is described.
The features of this condition include a short, deformed tibia; proximal
subluxation of the fibula at the knee; a normal knee joint and an ankle joint
that may look abnormal but falls short of true diastasis of the joint. Treatment
of two cases by differential lengthening of the tibia and fibula using the
Ilizarov device is described. This form of tibial hemimelia should be recognised
as a separate variant as preservation of the foot and ankle with expected
excellent function should be possible, unlike the more severe forms of this
condition.
PMID- 11008742
TI - Internal derotation osteotomy of the tibia: pre- and postoperative gait analysis
in persons with high sacral myelomeningocele.
AB - Rotational deformities of the lower extremities are common in patients with
myelomeningocele. In these situations, surgical correction is often necessary. We
conducted a retrospective review of eight ambulatory patients with high sacral
myelomeningocele and external tibial torsion who underwent 10 distal tibia and
fibular internal derotation osteotomies. All patients had an increased valgus
knee stress preoperatively. Pre- and postoperative three-dimensional gait
analysis was used to evaluate coronal plane knee moments and dynamic sagittal
plane knee motion. Postoperatively, a significant improvement in the abnormal
internal knee varus moment (p < 0.005) as well as a significant increase in the
stance phase knee extension (p < 0.01) was seen. Three patients had resolution of
preoperative knee pain. We believe that patients with increased knee stress
secondary to excessive external tibial torsion will benefit from a tibial
derotation osteotomy that could delay or prevent the onset of late degenerative
changes about the knee.
PMID- 11008743
TI - An examination of the knee function during gait in children with
myelomeningocele.
AB - In this retrospective study, 37 patients with myelomeningocele who had undergone
gait analysis were examined. Patients were divided into groups based on the level
of involvement (29 sides: L4; 26 sides: L5; 19 sides: S1-2). Results showed
increased knee flexion and associated knee extensor moments with increasing level
of neurologic involvement. The mean coronal plane knee position in stance was
normal in all groups and not related to coronal plane knee moment. However, there
was an increased incidence of a net knee adductor moment in stance with
increasing involvement (mean, 0.02 +/-0.18 N.m/kg for the L4 group). The presence
of a visual valgus thrust based on video records was not reliable in predicting
an abnormal knee coronal plane moment. An abnormal knee adductor moment in stance
was most highly related to coronal plane trunk motion (r = -0.62) and not tibial
torsion (r = -0.340). Increased transverse plane range of motion of the knee was
most highly related to transverse plane trunk motion (r = 0.67).
PMID- 11008744
TI - Radiographic abnormalities and clinical symptoms associated with patella alta in
ambulatory children with cerebral palsy.
AB - One hundred seventeen randomly selected, skeletally immature, ambulatory children
with spastic cerebral palsy were evaluated with clinical examination and lateral
radiographs of the knee. Radiographic abnormalities within either the patella or
the proximal tibia were present in 21% (41 knees) of the 193 affected knees. The
most common radiographic findings were elevation of the tibial tubercle in 34
knees and fragmentation of one pole of the patella in seven knees. Clinical
symptoms including pain, swelling, and tenderness were present in 32% of those
children with radiographic findings (13 of 41 knees). Patella alta was seen in
nearly all children in the study. The radiographic findings appeared to be
chronic, were usually asymptomatic, and have required no treatment to date.
PMID- 11008745
TI - Broomstick plaster with a removable abduction bar: a simple technique that
facilitates early postoperative physical therapy and handling.
AB - We present a simple technique utilising a broomstick plaster with a removable
abduction bar. This facilitates early postoperative physical therapy and handling
after surgery for lower limb problems in patients with cerebral palsy.
PMID- 11008746
TI - Evaluation of the walking pattern in clubfoot patients who received early
intensive treatment.
AB - The walking pattern in a group of nine adult male subjects who had received early
intensive treatment for congenital clubfoot was evaluated and compared to the
walking pattern in a control group of 15 adult healthy male subjects. All
subjects were filmed with a five-camera video system as they walked across two
force plates. A three-dimensional inverse dynamics approach was used to calculate
average joint angles, moments, power, and work. The results showed that there
were no differences in the joint angles between the two groups. The overall
patterns of the joint moments were very similar in the two groups. However,
analysis revealed a smaller ankle joint moment and larger knee and hip joint
moments in those with clubfoot. It was concluded that the larger knee and hip
joint moments served as compensation for the smaller ankle moment. The reduced
ankle moment and work developed about the ankle joint in the clubfeet could
possibly be owing to weaker plantar flexors. In conclusion, gait analysis can be
an important tool when evaluating treatment for clubfoot. However, further
investigation is needed to determine whether the higher hip and knee joint
moments observed in subjects with clubfoot may lead to the development of knee or
hip joint pathologies.
PMID- 11008747
TI - Comparison of the soft-tissue release methods in idiopathic clubfoot.
AB - The aim of this study was to compare the clinical and radiologic results of three
different surgical procedures (posterior release with lengthening of the tendo
calcaneus and posterior capsulotomy, Turco's technique of posteromedial release,
and Simons' technique of complete subtalar release) in idiopathic clubfoot in 77
patients who were operated on at 10 months of age or younger. The clinical
examination alone is not sufficient to determine the type of the surgical
intervention needed in idiopathic clubfoot; the decision must be supported by the
radiologic parameters (anteroposterior and lateral talocalcaneal, first
metatarsal-talar, and lateral tibiotalar angles) and all the components of the
multiplanar deformity must be corrected at the same time. Simons' technique of
complete subtalar release was found to be the most efficient method of surgery
both functionally and radiologically in cases of idiopathic clubfoot in infants.
The overcorrection of the deformity as a consequence of the concern that the
tarsal alignment did not improve adequately is a mistake we make not infrequently
and in our opinion this may be avoided by taking perioperative radiographs.
PMID- 11008748
TI - Talectomy for clubfoot in arthrogryposis.
AB - We reviewed the results of 101 talectomies in 56 patients with arthrogrypotic
clubfeet. The average age at the time of surgery was 4.3 years and the mean
follow-up was 6 years. Talectomy was performed as a primary procedure in 16 feet
and as a salvage procedure in 85 feet that underwent other surgical procedures
before talectomy. We graded our results as good when the foot was plantigrade,
able to wear regular shoes, pain free, and, very important, patient satisfaction.
We used a chi2 statistical test and, after comparing results with age <4 to >4
years at time of surgery, tendo Achilles tenotomy, time of casting, radiological
complete excision of talus, and transcalcaneal pin placement, only the
immobilization time needed to be statistically significant to achieve a good
result. We conclude that feet must be individualized for treatment and that,
after reduction of the calcaneus in the mortise, a short leg cast must be placed
for 8 weeks to maintain position and alignment.
PMID- 11008749
TI - Scoliosis in arthrogryposis multiplex congenita: results after nonsurgical and
surgical treatment.
AB - Forty-six patients (25 male and 21 female) with arthrogryposis multiplex
congenita who were seen at the Alfred I. duPont Hospital for Children between the
years 1940 and 1997 were evaluated to assess the prevalence and patterns of
scoliosis and the long-term results after both nonsurgical and surgical treatment
methods. We found the prevalence of scoliosis to be 65.9% (32 of 46 patients). A
single thoracolumbar curve was the predominant curve pattern. No congenital curve
types or vertebral anomalies were seen in our group of patients. In the
nonsurgical group, the mean curve was <30 degrees at follow-up. In the surgical
group, the mean primary curve before spinal arthrodesis was 78.5 degrees. Three
patients in the surgical group who were nonambulators have become household
ambulators at the most recent follow-up. We recommend bracing in patients who are
ambulators and have a curve of <30 degrees. Combined anterior and posterior
spinal arthrodesis gave the best results.
PMID- 11008750
TI - The induction of congenital spinal deformities in mice by maternal carbon
monoxide exposure.
AB - Carbon monoxide (CO) has been shown to be teratogenic in mice. High altitude
hypoxia has also been shown to induce congenital vertebral anomalies in mice. The
purpose of this study was to investigate the effect of maternal hypoxia owing to
CO exposure and the production of congenital spinal deformities in the offspring.
Sixty DBA-1J mice were bred using polygamous timed breeding methods. Pregnant
females were exposed to 200, 400, or 600 ppm CO using a custom-designed gas
blender system. Seven-hour exposures were performed on day 8.5, 9.5, or 10.5 of
the 21-day gestation cycle. The neonates were euthanized at birth; the specimens
were fixed, eviscerated, and radiographed. Congenital spinal deformities were
observed (wedge, hemi, fused, and missing vertebrae; fused ribs) and were located
in all regions of the spine. There was a statistically significant difference in
the number of spinal deformities between all groups, with no defects in the
controls and a 77% incidence at 600 ppm (p < 0.0001). There was no apparent
correlation between the time of exposure and defect location. The most sensitive
time of gestation was 9.5 days. We identified an animal model of congenital
spinal deformities that compares favorably with the evidence of human congenital
spinal deformities in cases of maternal exposure to CO and other gas and chemical
fumes.
PMID- 11008751
TI - Analysis of the STIF technique for spino-pelvic fixation: clinical results in 19
patients with neuromuscular scoliosis.
AB - The STIF (spinopelvic transiliac fixation) technique for lumbosacral fusion was
developed by the authors as an alternative to the Luque-Galveston technique. The
results observed in this initial series of 27 neuromuscular scoliosis patients
treated with the STIF technique are reported. With a minimum of 24 months of
radiographic follow-up in 19 patients, the percentage of correction of scoliosis
curvature and pelvic obliquity was superior to that reported in the literature.
The rates of complications and pseudarthrosis in this series are typical for this
patient population. The STIF technique facilitates compression across the
sacroiliac joints, which promotes sacroiliac joint fusion and can provide a
stable base for curvature correction and lumbosacral fusion. Despite the severe
coronal and sagittal plane curves in this group of patients, total operative time
also compares favorably to that reported in the literature. The STIF technique
requires a well-developed posterior iliac apophysis, which may not be present in
younger pediatric patients.
PMID- 11008752
TI - Cervical spondylolysis in children: is it posttraumatic?
AB - Cervical spondylolysis is a rare defect of unknown etiology. Five cases of
cervical spondylolysis as well as two cases of fractures of the pedicles of C2 in
infants are presented. Comparison of the cases suggests that a fracture at birth
or in infancy may be the cause of some cases of cervical spondylolysis.
PMID- 11008754
TI - Relationship of factors affecting age of onset of independent ambulation.
AB - Despite the standard available pediatric developmental scales and popular lore
that girls walk at an earlier age than boys, no large-scale evaluation of the age
of onset of independent ambulation has been previously published. The purpose of
this study was the prospective epidemiologic evaluation of a large heterogeneous
group of normal children to determine the effect of gender, race, birth order,
and socioeconomic status on the age of onset of independent ambulation. The study
cohort consisted of 986 children (575 male, 471 female). A multivariable analysis
of covariance model was used to examine the effects of race, gender, income, and
birth order on age at ambulation. After controlling for the other variables in
the model, race was the only statistically significant predictor of age at
ambulation (p < 0.0001), with black children walking at a younger age (10.9 +/-
2.1 months) than white children (11.6 +/- 2.3 months). Overall, the independent
variables included in the model were only able to explain 2.5% of the variance of
age at ambulation.
PMID- 11008753
TI - Retrospective review of osteoarticular infections in a pediatric sickle cell age
group.
AB - Patients with sickle cell disease have been documented to be particularly
susceptible to osteoarticular infections. Controversy exists concerning the
bacteriology, etiology, and clinical presentation in differentiating
osteoarticular infections from bone infarct. We retrospectively reviewed all
cases from our institution over the past 22 years of osteoarticular infections in
children who carry the diagnosis of sickle cell disease. Two thousand consecutive
patient charts of children enrolled in the Pediatric Sickle Cell Clinic of our
institution between 1973 and 1995 were evaluated. There were 14 cases of bone or
joint infections (10 osteomyelitis, four septic arthritis). There was one case of
multicentric osteomyelitis and one case of meningitis complicating the septic
arthritis. There were nine male and five female patients with ages ranging from 6
months to 17 years (mean, 8.0). All patients were noted to have hemoglobin SS.
The predominant presenting symptoms were pain (79% of cases) and swelling (71% of
cases). The most frequent physical findings were fever >38.2 degrees C (71% of
cases) and tenderness (86% of cases). Ninety-three percent of the children had a
white blood count exceeding 15,000/mm3 (range, 7,900-32,300). Westergren
sedimentation rates ranged from 14 to 89 mm/h with 93% of the children exceeding
the normal value in our hospital. Cultures were positive in 75% of tissue
biopsies, 58% of the blood cultures, and 70% of the bone or joint aspirates. The
most common offending organism found in osteomyelitis was Salmonella (eight of 10
cases); however, no predominant organism found was identified in cases of septic
arthritis. Radiographs and bone scans were of limited value in the differential
diagnosis between osteoarticular infections and bone infarction. Early diagnosis
and treatment of osteoarticular infections is key to satisfactory outcome. This
study suggests that an ill-appearing patient with a fever >38.2 degrees C, pain,
and swelling should prompt the physician to aspirate or biopsy the area and not
rely on diagnostic studies that we found to be unreliable.
PMID- 11008755
TI - Spontaneous regression of osteochondromatosis of the radius after lengthening of
the ulna: a case report.
AB - Despite the high incidence, the natural biologic behavior of the osteochondroma
is not yet known. In particular, the spontaneous regression of the exostosis is
very rare and as yet an undefined phenomenon. Since the first description by
Hunter in 1835, only 11 cases have been reported. On reviewing the reports in the
literature, all cases were regressed spontaneously without significant mechanical
stimuli such as surgical procedures. The reasons for the spontaneous regression
were not explained sufficiently. This study describes one additional case of the
spontaneous regression of osteochondromatosis of the radius and ulna after change
of the mechanical strain or stress with lengthening of the ulna in a patient with
multiple hereditary exostosis. The radiographic findings in this study are
presented with some hypotheses explaining this interesting phenomenon.
PMID- 11008756
TI - Abnormalities in the uninvolved lower limb in children with spastic hemiplegia:
the effect of actual and functional leg-length discrepancy.
PMID- 11008757
TI - A selective optical sensor based on [9]mercuracarborand-3, a new type of
ionophore with a chloride complexing cavity.
AB - A highly selective optical sensor for chloride, based on the multidentate Lewis
acid ionophore [9]mercuracarborand-3, is described herein. This sensor is
constructed by embedding the mercuracarborand ionophore, a suitable pH-sensitive
lipophilic dye, and lipophilic cationic sites in a plasticized polymeric
membrane. The multiple complementary interactions offered by the preorganized
complexing cavity of [9]mercuracarborand-3 is shown to control the anion
selectivity pattern of the optical film. The film exhibits a significantly
enhanced selectivity for chloride over a variety of lipophilic anions such as
perchlorate, nitrate, salicylate, and thiocyanate. Furthermore, the optical
selectivity coefficients obtained for chloride over other biologically relevant
anions are shown to meet the selectivity requirements for the determination of
chloride in physiological fluids, unlike previously reported chloride optical
sensors. In addition, the optical film responds to chloride reversibly over a
wide dynamic range (16 microM-136 mM) with fast response and recovery times.
PMID- 11008758
TI - Modeling interparticle and intraparticle (perfusive) electroosmotic flow in
capillary electrochromatography
AB - A model to estimate the extent of intraparticle, or perfusive, electroosmotic
flow (EOF) in CEC capillaries packed with macroporous particles has been
developed. Nucleosil packings (d(p) = 7 microm) having nominal pore sizes of 500,
1000, and 4000 A were studied. Intraparticle pores ranging from 50 to 10000 A in
diameter were partitioned into 995 intervals of 10 A. Using pore size
distribution data for the sorbents obtained by mercury intrusion porosimetry,
fractions of the total column void volume contributed by pores in the range of
interest were determined. The average channel diameter of the interstitial space
was estimated from the d(p) of the packing; its fraction of total column volume
was determined from the interstitial porosity. Estimations of relative EOF
velocity in the intraparticle and interstitial channels were made by treating the
channels as parallel cylindrical capillary tubes. Relative EOF values were
combined with the volume fraction data and used as weighting factors in
calculating an effective particle diameter (d(p,eff)) for each set of conditions
(i.e., packing type, ionic strength of eluent). Values of d(p,eff) generated by
the model correctly predict the trends observed in the experimental data. At the
lowest ionic strength, plate height correlated inversely with the pore size of
packing (h4000 A < h1000 A < h500 A). Rate curves for each column tended toward
lower plate heights with increasing eluent ionic strength before converging at
some limiting point. The point of convergence was reached at moderate ionic
strengths for the larger pore media (1000 and 4000 A) and higher ionic strength
for the 500 A.
PMID- 11008759
TI - Subfemtomole MS and MS/MS peptide sequence analysis using nano-HPLC micro-ESI
fourier transform ion cyclotron resonance mass spectrometry.
AB - Subfemtomole peptide sequence analysis has been achieved using microcapillary
HPLC columns, with integrated nanoelectrospray emitters, coupled directly to a
Fourier transform ion cyclotron resonance mass spectrometer. Accurate mass (+/
0.010 Da) peptide maps are generated from a standard six-protein digest mixture,
whose principle components span a concentration dynamic range of 1000:1.
Iterative searches against approximately 189000 entries in the OWL database
readily identify each protein, with high sequence coverage (20-60%), from as
little as 10 amol loaded on-column. In addition, a simple variable-flow HPLC
apparatus provides for on-line tandem mass spectrometric analysis of tryptic
peptides at the 400-amol level. MS/MS data are searched against approximately
280000 entries in a nonredundant protein database using SEQUEST. Accurate
precursor and product ion mass information readily identifies primary amino acid
sequences differing by asparagine vs aspartic acid (deltam = 0.98 Da) and
glutamine vs lysine (deltam = 0.036 Da).
PMID- 11008761
TI - Multichannel mode-filtered light detection based on an optical fiber for small
volume chemical analysis
AB - A novel mode-filtered light detection method is described in which an unjacketed
optical fiber is inserted into a transparent capillary tube and three or more
detection channels are set on the capillary side for different distances from the
port of the fiber. This new method is the basis of synchronization of separation
and analysis, with which a modern multidimensional analysis apparatus will be
constructed. For samples of different concentration, the more close to the laser
incidence port of the fiber the detector has been set up, the greater the change
of the intensity profile of mode-filtered light (deltaI(F)) that is obtained.
Vice versa, if a parameter alpha = I0/In is established and, instead of a mode
filtered light signal, the reversed alteration trend of deltaalpha is found in
comparison with the alteration trend of deltaI(F), the reason is that the
background rapidly lowers with the increasing distance to the laser incidence
port of the fiber; moreover, the mode-filtered light signal decreases slowly with
it. With the present method and apparatus, glucose and glycerol have been
determined, with good reproducibility and stability and a small sample volume.
Furthermore, a real sample of glucose injection is measured for a detection
volume of 5 microL, and an acceptable result is observed.
PMID- 11008760
TI - A mass spectrometry method for the determination of enantiomeric excess in
mixtures of D,L-amino acids.
AB - A mass spectrometry method based on ion/molecule reactions for determining
enantiomeric excess in mixtures of amino acids is illustrated. Protonated
complexes of amino acids with beta-cyclodextrin are produced in the gas phase
using electrospray ionization. Under a background pressure of N-propylamine, the
amino acid is replaced by the alkylamine. The rates of the guest exchange
reaction vary with the chirality of the amino acid. A calibration curve employing
varying mixtures of D- and L-amino acids is produced and the fractions of the D
isomer in the test mixtures are determined. The quality of the curve is compared
to the chiral selectivity of the reaction. In general, the best calibration
curves are obtained in systems with the greatest selectivity.
PMID- 11008762
TI - Detection and quantification of metals in organic materials by laser-SNMS with
nonresonant multiphoton ionization.
AB - We have shown that the sensitive detection and in favorable cases the
quantification of metals in organic materials by laser-SNMS with nonresonant
multiphoton ionization (NRMPI) is possible. As a model system, sputter-deposited
submonolayer coverages of metals on polymer surfaces (polycarbonate,
poly(vinylidene chloride), polyimide) were investigated. By use of these samples,
relative sensitivity factors and detection limits of several metals (Be, Cr, Mn,
Fe, Co, Ni, Mo, W) were determined using laser-SNMS with NRMPI. The relative
sensitivity factors for this kind of sample show a high level of agreement with
those for metals sputtered from alloys. The detection limits ( 1 ppm of a
monolayer) are almost the same as for inorganic matrixes such as Si or GaAs.
Laser-SNMS with NRMPI was also used for the determination of the elemental
composition of the active centers of metalloproteins (namely, the purple acid
phosphatases extracted from sweet potatoes and from red kidney beans). These
results have shown the ability of laser-SNMS to detect metal atoms bound to
organic macromolecules with an atom concentration as low as 1 ppm. In comparison
to TOF-SIMS, laser-SNMS is more sensitive for metal detection in organic
matrixes, since the secondary ion yields observed for these matrixes are reduced
compared to matrixes optimized for high secondary ion emission, such as, for
example, highly oxidized surfaces.
PMID- 11008763
TI - An assay for ascorbic acid based on polyaniline-coated microplates.
AB - A technique for modification of the microtiter reader plates well with a
polyaniline (PANI) film sensitive for ascorbic acid is presented. The principle
of the analyte detection is based on monitoring the changes in optical absorption
of the PANI film resulting from the reduction process initiated by ascorbic acid.
The detection limit for ascorbic acid is 1 mg/L. Testing with real samples (soft
drinks, fruit juices) gave good correlation of the method with iodimetric
titration. High sensitivity, stability, and good reproducibility of the
measurements make the proposed system an attractive alternative to traditional
assays, used in medicine, ecology, and biotechnology.
PMID- 11008764
TI - Fabrication, characterization, and enzymatic activity of encapsulated fungal
protease--fatty lipid biocomposite films.
AB - Encapsulation of an aspartic protease from the fungus Aspergillus saitoi (F-prot)
in thermally evaporated fatty acid films by a simple beaker-based immersion
technique under enzyme-friendly conditions is described. The approach is based on
diffusion of the enzyme from aqueous solution, driven primarily by attractive
electrostatic interaction between charged groups on the enzyme surface and
ionized lipid molecules in the film. The encapsulated enzyme molecules could be
"pumped out" of the biocomposite film into solution by modulating the
electrostatic interaction between the enzyme and fatty acid molecules via
solution pH variation. The kinetics of F-prot diffusion into the acid films was
followed using quartz crystal microgravimetry measurements while the secondary
and tertiary structure of the enzyme in the lipid matrix was studied using
Fourier transform infrared (FT-IR) and fluorescence spectroscopies. FT-IR and
fluorescence measurements indicated little perturbation to the native structure
of the enzyme. A chemical analysis of the F-prot-fatty acid biocomposite film was
also performed using X-ray photoelectron spectroscopy. The encapsulated F-prot
molecules showed catalytic activity (as estimated by reaction with hemoglobin)
comparable to free enzyme molecules in solution, indicating facile access of
biological analytes/reactants in solution to the enzyme molecules. The
advantages/disadvantages of this approach vis-a-vis methods currently used for
encapsulation of biomolecules are briefly discussed.
PMID- 11008765
TI - Multielement analysis of polyethylene using solid sampling electrothermal
vaporization ICP mass spectrometry
AB - Next to laser ablation (LA) also electrothermal vaporization (ETV) from a
graphite furnace as a means of sample introduction opens possibilities for direct
analysis of solid samples using inductively coupled plasma mass spectrometry
(ICPMS). In this paper, it is demonstrated that solid sampling ETV-ICPMS is very
well suited for the determination of metal traces in polyethylene. A limited
multielement capability is often cited as an important drawback of ETV-ICPMS.
However, by studying the effect of monitoring an increasing number of mass-to
charge ratios on the signal profile (integrated signal intensity and
repeatability) of selected analyte elements, the multielement capability of
(solid sampling) ETV-ICPMS was systematically evaluated, and the results obtained
suggest that, with a quadrupole-based ICPMS instrument, at least 11 elements can
be determined "simultaneously" (from the same vaporization step), in essence
without compromising the sensitivity or the precision of the results obtained. In
this work, the "simultaneous" determination of Al, Ba, Cd, Cu, Mn, Pb, and Ti in
a polyethylene candidate reference material has been accomplished, despite the
large variation in analyte concentration (from 5 ng/g for Mn to 500 microg/g for
Ti) and in furnace behavior (volatility) they exhibit. To avoid premature losses
of Cd during thermal pretreatment of the samples, Pd was used as a chemical
modifier. Two different calibration methods--external calibration using an
aqueous standard solution and single standard addition--were studied and the
results obtained were compared with those obtained using neutron activation
analysis (NAA) and/or with the corresponding (candidate) certified values (if
available). Single standard addition was shown to be preferable (average
deviation between ICPMS result and reference value < 3%), although--except for Ba
-acceptable results could also be obtained with external calibration.
PMID- 11008766
TI - Monitoring electroosmotic flow by periodic photobleaching of a dilute, neutral
fluorophore
AB - Electroosmotic flow has been monitored in a capillary using a method based on
periodic photobleaching of a neutral, fluorescent buffer additive. Rhodamine B
was determined to be neutral between pH 6.0 and 10.8 and was added to the running
buffer at a concentration of 400 nM. Rhodamine B was photobleached by opening a
shutter under computer control for 250 ms every 5.00 s, to expose the dye to a
laser beam and create a photobleached zone. The time was measured for the
photobleached zone to migrate 6.13 mm to a downstream laser-induced fluorescence
detector, to determine the rate of electroosmotic flow in the entire capillary.
The flow rate was sampled every 5.00 s, and the precision of the flow
measurements was 0.7% or better. Three fluorescent compounds were separated and
detected by capillary electrophoresis with laser-induced fluorescence detection,
while simultaneously monitoring the electroosmotic flow rate.
PMID- 11008767
TI - Analysis of alkylphenol ethoxylate metabolites in the aquatic environment using
liquid chromatography-electrospray mass spectrometry.
AB - A quantitative method is described for the analysis of the metabolites of
alkylphenol ethoxylate (APEO) surfactants in estuarine water and sediment samples
using reversed-phase high-performance liquid chromatography with electrospray
mass spectrometry detection. Nonyl- and octylphenols, nonyl- and octylphenol mono
, di-, and triethoxylates, halogenated nonylphenols, and nonylphenol
ethoxycarboxylates were concentrated from water samples using a C18 solid-phase
extraction procedure. A novel, continuous-flow, high-temperature, sonicated
extraction system was developed to isolate APEO metabolites from sediment
samples. Quantitative LC-MS was performed in the negative ion mode for
nonylphenols, octylphenols, and halogenated nonylphenols and in the positive ion
mode for nonyl- and octylphenol ethoxylates using selected ion monitoring with
isotopically labeled surrogate standards. Recoveries for sediment and water
analyses ranged between 78 and 94%, and detection limits for APEO metabolites
were between 1 and 20 pg injected on column. This is a significant improvement
over previously reported methods. Suppression of analyte response was encountered
in the presence of matrix components in sediment samples, but this effect was
eliminated by careful selection of surrogate and internal standards. Individual
APEO metabolite concentrations of 1-320 ng/L and 5-2000 ng/g are reported for
water and sediment samples, respectively, from Jamaica Bay, NY.
PMID- 11008768
TI - Modeling of sample dynamics in rectangular asymmetrical flow field-flow
fractionation channels
AB - We model the evolution of the concentration field of macromolecules in a
rectangular asymmetrical flow field-flow fractionation channel using center
manifold techniques. The deviation of the primary flow from a parabolic profile
influences the concentration field and this is investigated to complement
previously known results. The long-term evolution of the components of the sample
is shown to be well described by a one-dimensional advection-diffusion equation.
The coefficients of this equation are determined by the rigorous analysis of the
complete set of equations governing the two-dimensional fluid flow. This model
gives quantitative predictions of the elution time of the samples, the width of
the concentration pulse, and the resolution of the apparatus. The influence of
initial sample width and effects of the secondary relaxation from focusing to
elution conditions are discussed. Reported theoretical predictions are in
agreement with experimental results published previously.
PMID- 11008769
TI - Comprehensive two-dimensional gas chromatography via differential flow modulation
AB - A novel comprehensive two-dimensional gas chromatograph has been developed that
utilizes differential flow modulation. This technique uses a 6-port valve to
collect effluent from a primary column and periodically inject the effluent into
a secondary column. The flow in the secondary column is kept 20 times larger than
the flow in the primary column so the contents of the sample loop can be flushed
into the secondary column in 5% of the collection time. Peaks widths at half
maximum of approximately 0.06 s are generated for a 1.0 Hz secondary injection
frequency. Sensitivity is not compromised, as 80% of the sample passes through
both columns and reaches the detector. This simple yet effective technique has
been used to analyze mixtures of alkanes, alkenes, aldehydes, alcohols,
aromatics, esters, and ketones with high speed and high resolution.
PMID- 11008770
TI - Monte Carlo model of nonlinear chromatography
AB - A stochastic approach to the nonlinear chromatography theory, based on the Monte
Carlo simulation method, is presented. A computer program, acting as a "virtual
chromatograph" and performing a discrete event simulation, is described. Such a
program allows one to choose the column type, operating conditions, sample
composition, injection method, mobile-phase dispersion model, and stationary
phase sorption-desorption kinetics. Nonlinearity is accounted for by continuously
monitoring and updating both the column and the solute status and by moving
individual molecules step by step along the column according to specific random
modes. The program has been validated through a series of statistical tests and
comparing the results with the well-known achievements of the classical
stochastic theory. A first application is presented, referred to a real case
benzene elution on a gas solid capillary column, where the Langmuir adsorption
isotherm is assumed. The effect of both the sorption modes and the site capacity
are investigated. Possible applications to investigate open problems in several
fields of separation science are emphasized. In addition, several specific points
such as the down-scaling of a real case and the correspondence of specific
adsorption dynamics with the equilibrium Langmuir isotherm are described.
PMID- 11008771
TI - Resolving and quantifying overlapped chromatographic bands by transmutation
AB - A new chemometric technique called "transmutation" is developed for the purpose
of sharpening overlapped chromatographic bands in order to quantify the
components. The "transmutation function" is created from the chromatogram of the
pure component of interest, obtained from the same instrument, operating under
the same experimental conditions used to record the unresolved chromatogram of
the sample mixture. The method is used to quantify mixtures containing toluene,
ethylbenzene, m-xylene, naphthalene, and biphenyl from unresolved chromatograms
previously reported. The results are compared to those obtained using window
factor analysis, rank annihilation factor analysis, and matrix regression
analysis. Unlike the latter methods, the transmutation method is not restricted
to two-dimensional arrays of data, such as those obtained from HPLC/DAD, but is
also applicable to chromatograms obtained from single detector experiments.
Limitations of the method are discussed.
PMID- 11008772
TI - Multidimensional analysis of poly(ethylene glycols) by size exclusion
chromatography and dynamic surface tension detection
AB - Substantial improvements in a multidimensional dynamic surface tension detector
(DSTD) are presented. Rapid, online calibration and measurement of the dynamic
surface tension for high-performance liquid chromatography separations is
achieved. Dynamic surface tension is determined by measuring the differential
pressure across the liquid-air interface of repeatedly growing and detaching
drops. Continuous surface tension measurement throughout the entire drop growth
(50 ms to 2 s) is achieved, for each eluting drop, providing insight into the
kinetic behavior of molecular orientation processes at the liquid-air interface.
Three-dimensional data are obtained, with surface tension first converted to
surface pressure, which is plotted as a function of elution time axis versus drop
time axis. Two key innovations will be reported. First, a novel calibration
procedure is described and implemented. Differential pressure signals from three
drops (mobile phase, standard in mobile phase, and analyte in mobile phase) are
utilized to make the dynamic surface tension measurement, thereby eliminating the
need for optical imaging, and viscosity and hydrostatic pressure corrections, as
required by other methods. Only pressure signals from one mobile-phase drop and
one standard drop pressure signal are required, while the analyte drop pressure
signal is measured along the chromatographic time axis. Second, corrections for
drop elongation are not required, because the drops are precisely detached by an
air burst actuation method in a regime were the surface tension forces
significantly dominate gravitational forces. Drops that would fall with a volume
of approximately 10 microL due to gravity are precisely and repeatedly detached
earlier at a volume of 2 microL. The sensitivity and unique selectivity of the
DSTD opens up new possibilities in the analysis of small molecular weight
polymers of varying degrees of surface activity, as illustrated for the size
exclusion chromatography analyses of complex poly(ethylene glycol) (PEG) samples.
Using partial least squares for data analysis, polydispersity of complex PEG
samples is determined at a relative precision of approximately 1%.
PMID- 11008773
TI - Chemical grafting of molecularly imprinted homopolymers to the surface of
microplates. Application of artificial adrenergic receptor in enzyme-linked assay
for beta-agonists determination.
AB - A technique for coating of microplate wells with a molecularly imprinted polymer
(MIP), specific for epinephrine, is presented. 3-Aminophenylboronic acid was
polymerized in the presence of epinephrine using oxidation of the monomer by
ammonium persulfate. This process resulted in the grafting of a thin polymer
layer onto the polystyrene surface of the microplates. The polymer affinity was
determined by an enzyme-linked assay using a conjugate of horseradish peroxidase
and norepinephrine (HRP-N). It was found that imprinting resulted in increased
affinity of the polymer toward HRP-N and epinephrine. Influence of the buffer pH
and concentration on the polymer affinity was analyzed. It was shown that the MIP
coated microplates could be used for assay development and drug screening. The
high stability of the polymers and good reproducibility of the measurements make
MIP coating an attractive alternative to traditional antibodies or receptors,
used in ELISA.
PMID- 11008774
TI - High-performance liquid chromatography-electrospray ionization mass spectrometry
of single- and double-stranded nucleic acids using monolithic capillary columns.
AB - Monolithic capillary columns were prepared by copolymerization of styrene and
divinylbenzene inside a 200-microm i.d. fused silica capillary using a mixture of
tetrahydrofuran and decanol as porogen. With gradients of acetonitrile in 100 mM
triethylammonium acetate, the synthesized columns allowed the rapid and highly
efficient separation of single-stranded oligodeoxynucleotides and double-stranded
DNA fragments by ion-pair reversed-phase high-performance liquid chromatography
(IP-RP-HPLC). Compared with capillary columns packed with micropellicular,
octadecylated poly-(styrene/divinylbenzene) particles, an improvement in column
performance of approximately 40% was obtained, enabling the analysis of an 18-mer
oligodeoxynucleotide with a column efficiency of more than 190000 plates per
meter. The chromatographic separation system was on-line-coupled to electrospray
ionization mass spectrometry (ESI-MS). To improve the mass spectrometric
detectabilities, 25 mM triethylammonium bicarbonate was utilized as an ion-pair
reagent at the cost of only little reduction in separation performance and
acetonitrile was added postcolumn as the sheath liquid through the triaxial
electrospray probe. High-quality mass spectra of femtomole amounts of 3-mer to 80
mer oligodeoxynucleotides were recorded showing very little cation adduction.
Double-stranded DNA fragments ranging in size from 51 to 587 base pairs were
separated and detected by IP-RP-HPLC-ESI-MS. Accurate mass determination by
deconvolution of the mass spectra was feasible for DNA fragments up to the 267
mer with a molecular mass of 165 019, whereas the spectra of longer fragments
were too complex for deconvolution because of incomplete separation due to
overloading of the column. Finally, on-line IP-RP-HPLC tandem MS was applied to
the sequencing of short oligodeoxynucleotides.
PMID- 11008775
TI - Evaluation of a vancomycin chiral stationary phase in capillary
electrochromatography using polar organic and reversed-phase modes.
AB - A vancomycin chiral stationary phase (CSP) was fully evaluated in capillary
electrochromatography (CEC) in reversed-phase and polar organic modes for a
number of racemic pharmaceutical compounds. High efficiency and resolution values
were obtained for a number of compound classes including thalidomide in both the
polar organic mode (190000 plates meter(-1) and Rs = 13.8) and reversed-phase
mode (125000 plates meter(-1) and Rs = 13.0). Experimental parameters, including
organic modifier, organic solvent ratio, ionic strength, pH, temperature, and
voltage, were examined in both the aqueous and nonaqueous modes to deduce their
effect on the resultant EOF, retention times, resolution, and efficiency of
chiral separations. All results were consistent with and found to be a
combination of what is known from existing literature on CEC theory and
experience obtained with macrocyclic antibiotic CSPs in LC. Column stability was
excellent, and each column packed was found to offer repeatable separations even
when switching from the aqueous to the nonaqueous mode.
PMID- 11008776
TI - Determination of arsenic compounds by high-performance liquid chromatography
ultrasonic nebulizer-high power nitrogen-microwave-induced plasma mass
spectrometry: an accepted coupling.
AB - To establish a sensitive, accurate, and precise determination of arsenic
compounds, a high power nitrogen microwave-induced plasma (1.3 kW) mass
spectrometer (N2-MIP-MS) has been successfully coupled with an ultrasonic
nebulizer (HPLC-USN) that is attached to a high-performance liquid chromatograph.
It is examined as an element-specific detector for its applicability to the
optimization and determination of seven arsenic compounds [arsenic acid,
methylarsonic acid (MA), dimethylarsinic acid (DMA), arsenobetaine (AB),
arsenocholine (AC), trimethylarsine oxide (TMAO), and tetramethylarsonium ion
(CMI)]. This HPLC-USN-MIP-MS coupling is an encouraging combination as an
alternative method for mass spectroscopy for elemental speciation analysis.
Interchanging of the MIP-MS fabricated nebulizer (concentric) with an ultrasonic
nebulizer, increases 3-6 times the ion signals for the anionic and 6-12 times
those for the cationic arsenic compounds as compared to traditional methods. The
HPLC-USN-MIP-MS combination used is excellent, amplifying the ion signals about
1.5-2 times for cationic and 1.3-2.8 times for the anionic arsenic compounds as
compared to the HPLC-ICPMS coupling. The detection limits for As(V), MA, DMA, AB,
TMAO, AC, and TMI (in Milli-Q-water) obtained with the optimized HPLC-USN-N2-MIP
MS system are 0.46, 0.36, 0.73, 0.21, 3.64, 0.39, and 0.32 microg L(-1),
respectively, about 13-50 times lower than the HPLC-MIP-MS and about 3-11 times
lower than the HPLC-ICPMS. The detection limits of As(V), MA, DMA, AB, TMAO, AC,
and TMI, which spike in the urine, are deteriorated by 1.7-4.2 times compared
with the detection limits of the seven different As compounds, which are prepared
in the Milli-Q-water. The repeatability (RSD for three successive analyses) and
reproducibility (RSD for three successive analyses performed on three different
days), considering peak area and peak height, achieved for seven different
arsenic compounds are 0.5-7 and 0.7-8%, comparable with the HPLC-ICPMS (0.3-8.5%;
4-12%) and HPLC-MIP-MS (0.4-9%; 5-12%) systems. The combined HPLC-USN-N2-MIP-MS
has been adequately applied to the determination of AB in NIES Candidate Human
Urine CRM. The results agree with the HPLC-ICPMS values. Chloride interference as
40Ar35Cl+ is not found in the urine and with the high chloride matrix (10000 mg
L(-1)).
PMID- 11008777
TI - Quaternized trimethylaminated polystyrene-coated zirconia as a strong anion
exchange material for HPLC.
AB - The synthesis and characterization of a new, base-stable, strong anion exchange
phase by amination of polystyrene-coated zirconia (PS-ZrO2) are described. Even
though the ion exchange capacity of the quaternized trimethylaminated PSZrO2
(QTMA-PS-ZrO2) is only 0.07 mequiv/g, it is able to separate various inorganic
anions, benzoic acid derivatives, and nucleotides in their deprotonated states.
The effects of ionic strength, eluent pH, and counterion type are discussed. In
the presence of both phosphate and fluoride ions in the eluent, band broadening
caused by Lewis acid/base interactions between zirconia and analytes is greatly
suppressed. The mixed retention modes (ion exchange, hydrophobic interaction, and
Lewis acid/base interactions) on QTMA-PS-ZrO2 offer a different selectivity
toward various anionic analytes than do other zirconia- and nonzirconia-based ion
exchangers.
PMID- 11008778
TI - Functionalization of a poly(amidoamine) dendrimer with ferrocenyls and its
application to the construction of a reagentless enzyme electrode.
AB - Poly(amidoamine) dendrimers having various degrees of modification with the redox
active ferrocenyls were prepared by controlling the molar ratio of
ferrocenecarboxaldehyde to amine groups of dendrimers. By alternate layer-by
layer depositions of partial ferrocenyl-tethered dendrimers (Fc-D) with periodate
oxidized glucose oxidase (GOx) on a Au surface, an electrochemically and
enzymatically active multilayered assembly of enzyme was constructed. The
resulting GOx/Fc-D multilayer-associated electrodes were electrochemically
analyzed, and the surface concentration of ferrocenyl groups, active enzyme
coverage, and sensitivity were estimated. A 32% dendrimer modification level of
surface amines to ferrocenyls was found to be an optimum in terms of enzyme
dendrimer network formation, electrochemical interconnectivity of ferrocenyls,
and electrode sensitivity. With the prepared Fc(32%)-tethered dendrimers, mono-
and multilayered GOx/Fc-D electrodes were constructed, and their electrochemical
and catalytic properties were characterized. The bioelectrocatalytic signals from
the multilayered GOx/Fc-D electrodes were shown to be directly correlated to the
number of deposited bilayers. From this result, it seems that the electrode
sensitivity is directly controllable, and the multilayer-forming strategy with
partial ferrocenyl-tethered dendrimers is useful for the construction of
reagentless biosensors.
PMID- 11008779
TI - Nanoparticle characterization in nanoliter volumes by grating light reflection
spectroscopy
AB - We present both theoretical and experimental results demonstrating that grating
light reflection spectroscopy (GLRS) can provide information about the
concentration and average size of particles of nanometer dimensions distributed
in liquid-phase media. To demonstrate this, we have performed experiments on
various concentrations of dendrimeric oligomers in water. Our results show that,
with GLRS, we can determine the mean radius of particles with sizes on the order
of molecular dimensions. The measurements were carried out in a continuous-flow
format using a microchannel flow system and in a detection volume of less than
200 nL
PMID- 11008780
TI - Reduction of mass bias and matrix effects in inductively coupled plasma mass
spectrometry with a supplemental electron source in a negative extraction lens
AB - Electrons from a heated tungsten filament are created inside the extraction lens
and driven out toward the skimmer. These electrons move through the ion path and
reduce space charge effects between positive ions in the beam. The ion
transmission efficiency is improved by factors of two (for Pb+) to 27 (for Li+).
The greater sensitivity improvement for low-mass ions leads to a substantial
reduction in mass bias. With the additional electrons, MO+/M+ and M2+/M+
abundance ratios increase but can be minimized with a small reduction in aerosol
gas flow rate. No new background ions are observed with this technique. Matrix
effects can be significantly diminished when the electron source is operated
under the high electron current mode. The mass dependence of matrix-induced
suppression of analyte signals is essentially eliminated. Using flow injection
analysis to minimize solid deposition, the technique can tolerate Na matrix up to
10000 ppm (1%) with only approximately 15% loss of analyte sensitivity.
PMID- 11008781
TI - Electrochemical characterization of electrodes with submicrometer dimensions
AB - The construction and electrochemical characterization of electrodes with
submicrometer dimensions (2 nm < r(app) < 1000 nm) is reported. Electrodes are
prepared by insulating etched Pt wires with electrophoretic paint, as recently
reported by Slevin et al. (Electrochem. Commun. 1999, 1, 282). The voltammetric
behavior of these electrodes was evaluated using nine different redox systems;
well-defined and stable diffusion-limited responses were obtained in all but two
cases. The behavior of these electrodes was investigated in aqueous
ferrocenylmethyltrimethylammonium (FcTMA+) solutions in the presence and absence
of excess supporting electrolyte to determine the influence of diffusion and
migration on molecular transport in the nanometer spatial regime. Our findings
indicate that the voltammetric behavior of these electrodes can be described
using classical transport theory for r(app) > 10 nm.
PMID- 11008782
TI - Direct in situ measurements of labile inorganic and organically bound metal
species in synthetic solutions and natural waters using diffusive gradients in
thin films.
AB - The emerging technique of DGT (diffusive gradients in thin films) is shown to be
capable of performing new speciation measurements in situ in natural waters. In
DGT, metals are bound to a resin layer after passing through a well-defined
diffusion layer. Cd was measured in solutions containing glycine, EDTA, and
fulvic (FA) and humic acids (HA) by atomic absorption spectroscopy (AAS), anodic
stripping voltammetry (ASV), and DGT. DGT measured similar labile fractions to
ASV, with detailed differences being consistent with a thicker diffusion layer
allowing more dissociation of labile complexes and a slower diffusion of FA and
HA complexes through the gel. When single measurements are made in complex
solutions with DGT, precise quantification is impossible due to uncertainties
concerning the distribution of species with different diffusion coefficients. A
new procedure was proposed based on the advantage of DGT of being able to control
the pore size of the diffusive gel layer. Small (inorganic) species diffuse
freely through all gels but larger FA and HA (organic) complexes diffuse less
freely in more constrained gels. When measurements were made on known solutions
of Cu and FA or HA, it was possible to quantify the inorganic and organic species
separately. They agreed well with predictions made using the WHAM speciation
code. Multiple DGT units were also deployed in situ in a stream with high
dissolved organic carbon (14.6 mg/L). The systematic differences between the
devices with different gel compositions enabled determination, for the first
time, of the in situ concentrations of both labile inorganic and organic species
in natural water. A single DGT device with a constrained gel can be used to
quantify inorganic species directly, providing absolute accuracy is not required.
This ability of DGT to measure well-defined fractions of metals in situ using a
simple device gives it considerable potential as a regulatory tool. A direct
speciation measurement may be preferable to modeling approaches which require
diverse input data that are difficult to determine.
PMID- 11008783
TI - Determination of hydroxytyrosol in plasma by HPLC.
AB - Hydroxytyrosol (2-(3,4-dihydroxyphenyl)ethanol), a phenolic compound present in
extravirgin olive oil, has been reported to contribute to the prevention of
cardiovascular disease. The present study describes an accurate and reproducible
reversed-phase HPLC method to measure hydroxytyrosol in plasma. This compound was
extracted from acidified plasma by solid-phase extraction using an Oasis HLB
copolymer. The plasma sample was rinsed with water and methanol in water (5:95;
v/v). Hydroxytyrosol was eluted with methanol, which was subsequently evaporated
under a nitrogen stream. Analysis by HPLC with diode array-UV detection was
carried out using a C18 column and a gradient elution with acidified water and
methanol/acetonitrile (50:50; v/v). The method was validated by the analyses of
plasma samples spiked with pure hydroxytyrosol, obtaining a linear correlation
(0.9986) and precision with a coefficient of variation ranging from 0.79 to
6.66%. The recovery was approximately 100%, and the limit of detection was 37
ng/mL. The oral administration of hydroxytyrosol to rats and its subsequent
detection in plasma showed that the method is suitable for pharmacokinetic
studies.
PMID- 11008784
TI - Continuous-flow microextraction exceeding 1000-fold concentration of dilute
analytes
AB - A novel liquid-liquid microextraction method, that we have termed continuous-flow
microextraction (CFME), is described. In a 0.5-mL glass chamber, an organic drop
(1-5 microL) is held at the outlet tip of a polyetheretherketone (PEEK)
connecting tubing which is immersed in a continuously flowing sample solution and
acts as the fluid delivery duct and as a solvent holder. Extraction takes place
between the organic drop and the flowing sample solution that is continuously
ejected out of the PEEK tubing. Concentration factors of between 260- to 1600
fold are achieved within 10 min of extraction. Aspects relevant to CFME were
studied. In combination with gas chromatography-electron capture detection, CFME
allows analytes to be detected at femtogram-per-milliliter levels. The
performance of this technique was evaluated on the basis of the analysis of trace
nitroaromatic compounds and chlorobenzenes in environmental samples.
PMID- 11008785
TI - A planar pCO2 sensor with enhanced electrochemical properties.
AB - To develop planar microchemical pCO2 sensing devices with improved
electrochemical properties, we combined two advanced technologies. One is a
differential sensor arrangement to simplify the microfabrication procedure by
employing pH-sensitive gas-permeable membranes, and the other is the use of an
enzyme (carbonic anhydrase) to shorten total measurement time by accelerating the
rate of CO2 hydration. The adhesion of the polyurethane-matrix gas-permeable
membrane is enhanced significantly by incorporating a silanizing reagent (silicon
tetrachloride), improving the stability and extending sensor lifetime. The
proposed differential pCO2 microelectrodes exhibited significantly improved
performance in their preconditioning period, response and recovery times,
stability, response slope, and lifetime.
PMID- 11008786
TI - Rapid identification of the bacterial pathogens responsible for urinary tract
infections using direct injection CE.
AB - The use of high-performance capillary electrokinetic techniques for the
separation, identification, and quantitation of intact microbes represents a new
frontier for separation science. In this work, it is demonstrated that pathogens
most responsible for urinary tract infections can be distinguished from one
another after direct injection of untreated urine. High efficiencies (often
exceeding 1000000 plates/m) and short analysis times (< 10 min) are
characteristics of this approach. The concentration of the urine matrix appears
to be able to cause a small, but definite, change in the electroosmotic flow
velocity. This high-efficiency separation-based approach could prove to be
invaluable for the diagnosis and tracking of certain diseases. It also could form
the basis for a variety of rapid microbial assays.
PMID- 11008787
TI - Environmental mass spectrometry.
PMID- 11008788
TI - Dynamic electrochemistry: methodology and application.
PMID- 11008790
TI - Kenneth Stevens receives National Medal of Science
PMID- 11008792
TI - Reviews of acoustical patents
PMID- 11008789
TI - Chiral separations.
PMID- 11008791
TI - ASA presents special awards to young scientists at the 51st annual International
Science and Engineering Fair (ISEF). Acoustical Society of America
PMID- 11008793
TI - A three-dimensional, two-way, parabolic equation model for acoustic
backscattering in a cylindrical coordinate system
AB - A new PE model for solving three-dimensional, forward and backward sound
propagation in a cylindrical coordinate system is presented. The model marches a
wave field in the radial direction including the azimuthal diffraction effects,
and solves for a backscattered field based on a three-dimensional, single
scattering approach. A periodic sidewall boundary condition is applied for
computations in a 360-degree sector, while an approximate sidewall boundary
condition is used for calculation in a sector less than 360 degrees. These two
sidewall boundary conditions are verified by the numerical results. The major
drawback of using the cylindrical coordinate system, when the backscattering
solution is valid within a limited area, is analyzed using a geometrical-optical
interpretation. The model may be useful for studying three-dimensional
backscattering phenomena comprising azimuthal diffraction effects.
PMID- 11008794
TI - Quantitative imaging using a time-domain eigenfunction method
AB - An inverse scattering method that uses eigenfunctions of a scattering operator at
a single frequency is extended to include the full range of frequencies present
in the incident pulse waveform. The resulting so-called time-domain eigenfunction
method is shown to yield a modulated version of the scattering potential. The
potential is recovered by a demodulation process using cross correlation with a
reference. Including an adaptive delay in the reference is shown to compensate
partially for the linearization of the Born approximation and to extend its valid
range. The k-space window of the time-domain solution is expressed in terms of
the incident waveform and shown to be smoother than that of a single-frequency
solution. The time-domain method is examined using both calculated and measured
data. In the calculations, an exact solution for scattering from one or multiple
nonconcentric cylinders is used to obtain the scattered field. In the
measurements, a novel ring-transducer system was employed to obtain the incident
and total fields. The results of simulations and experiments show that the method
is robust and accurate for the size of objects considered and that the point
resolution approaches one-half the wavelength at the pulse center frequency.
PMID- 11008795
TI - Scattering of antiplane shear waves by a circular cylinder in a traction-free
plate
AB - Following a well-established formula used by many researchers, the scattering of
an anti-plane shear wave by an infinite elastic cylinder of arbitrary relative
radius centered in a traction-free two-dimensional isotropic plate has been
examined. The plate is divided into three regions by introducing two imaginary
planes located symmetrically away from the surface of the cylinder and
perpendicular to surfaces of the plate. The wave field is expanded into cylinder
wave modes in the central bounded region containing the cylinder, while the
fields in the other two outer regions are expanded into plate wave modes. A
system of equations determining the expansion coefficients is obtained according
to the traction-free boundary conditions on the plate walls and the stress and
displacement continuity conditions across the imaginary planes. By taking an
appropriate finite number of terms of the infinite expansion series and a few
selected points on the two properly chosen virtual planes and the surfaces of the
plate through convergence and precision tests, a matrix equation to numerically
evaluate the expansion coefficients is found. The method of how to choose the
locations of the imaginary planes and the terms of the expansion series as well
as the points on each respective boundary is given in Sec. III in detail. Curves
of the reflection and transmission coefficients against the relative radius of
the cylinder in welded and slip or cracked interfacial conditions are shown.
Analysis on the contrast variations of the reflection and transmission
coefficients for a cylinder in bonded and debonded interfacial situations is
made. The relative errors estimated by the deviation of the numerical results
from the principle of the conservation of energy are found to be less than 2%.
PMID- 11008796
TI - On approximating guided waves in plates with thin anisotropic coatings by means
of effective boundary conditions
AB - In this paper, effective boundary conditions for elastic wave propagation in
plates with thin coatings are derived. These effective boundary conditions are
used to obtain an approximate dispersion relation for guided waves in an
isotropic plate with thin anisotropic coating layers. The accuracy of the
effective boundary conditions is investigated numerically by comparison with
exact solutions for two different material systems. The systems considered
consist of a metallic core with thin superconducting coatings. It is shown that
for wavelengths long compared to the coating thickness there is excellent
agreement between the approximate and exact solutions for both systems.
Furthermore, numerical results presented might be used to characterize coating
properties by ultrasonic techniques.
PMID- 11008797
TI - Acoustic streaming in annular thermoacoustic prime-movers
AB - The theory of acoustic streaming in an annular thermoacoustic prime-mover is
developed. It is predicted that above the threshold for traveling wave excitation
the device considered (which does not contain any moving parts or externally
imposed pressure gradients) produces circulation of fluid. The heat flux carried
by this directional mass flow inside the thermoacoustic stack exceeds (or is
comparable with) the heat flux associated with the acoustically induced increase
of thermal diffusivity of the gas. The effects investigated are important for
optimization of the performance of thermoacoustic devices.
PMID- 11008798
TI - Measurement of a third-order elastic constant in silicon by a comparison method
AB - The third-order elastic constant C111 of silicon is measured with a comparison
method, based on the interaction between longitudinal acoustic waves. The value
is in good agreement with published values and demonstrates the validity of the
method.
PMID- 11008799
TI - Effective impedance of rough porous ground surfaces
AB - Laboratory measurements at grazing angles of the impedance of sand surfaces
containing artificial two-dimensional (2D) roughness are compared with
predictions of an extended boss theory, which allows for incoherent scatter,
randomness, and finite impedance effects. The data and predictions are found to
be in reasonable agreement. The rough surface impedance model may be used, as an
alternative to layering, to explain measurements where the reactance exceeds the
resistance at low frequencies. The model also explains instances where the
measured ground impedance tends to zero at higher frequencies. In addition, the
model is found to predict features of measurements made with an elevated source
and vertically separated receivers at a range of 30 m over cultivated ground
surfaces.
PMID- 11008800
TI - Acoustic field variability induced by time evolving internal wave fields
AB - A space- and time-dependent internal wave model was developed for a shallow water
area on the New Jersey continental shelf and combined with a propagation
algorithm to perform numerical simulations of acoustic field variability. This
data-constrained environmental model links the oceanographic field, dominated by
internal waves, to the random sound speed distribution that drives acoustic field
fluctuations in this region. Working with a suite of environmental measurements
along a 42-km track, a parameter set was developed that characterized the
influence of the internal wave field on sound speed perturbations in the water
column. The acoustic propagation environment was reconstructed from this set in
conjunction with bottom parameters extracted by use of acoustic inversion
techniques. The resulting space- and time-varying sound speed field was
synthesized from an internal wave field composed of both a spatially diffuse
(linear) contribution and a spatially localized (nonlinear) component, the latter
consisting of solitary waves propagating with the internal tide. Acoustic
simulation results at 224 and 400 Hz were obtained from a solution to an elastic
parabolic equation and are presented as examples of propagation through this
evolving environment. Modal decomposition of the acoustic field received at a
vertical line array was used to clarify the effects of both internal wave
contributions to the complex structure of the received signals.
PMID- 11008801
TI - Tomographic inversion for sediment parameters in shallow water
AB - This article discusses inversions for bottom geoacoustic properties using
broadband acoustic signals obtained from explosive sources. The experimental data
used for the inversions are SUS charge explosions acquired on a vertical
hydrophone array during the Shelf Break Primer Experiment conducted south of New
England in the Middle Atlantic Bight in August 1996. The SUS signals were
analyzed for their time-frequency behavior using wavelets. The group speed
dispersion curves were obtained from the wavelet scalogram of the SUS signals. A
genetic algorithm (GA) was used for the inversion of sound speeds in the water
column and compressional wave speeds in the sediment layers. The variations in
the sound speeds in the water column were represented using empirical orthogonal
functions (EOFs). A range-independent normal mode routine was used to construct
the replica fields corresponding to the parameters. Comparison of group speeds
for modes 1 to 9 and for a range of frequencies 8 to 200 Hz was used to arrive at
the best parameter fit. An efficient hybrid optimization scheme using the GA and
a Levenberg-Marquardt algorithm is presented. Linear perturbation methods were
also used to "fine tune" the inversions and to obtain resolution and variance
estimates. Analysis was also done to compute the degree of convergence of each of
the parameters by explicitly calculating the Hessian matrices numerically. A
posteriori estimation of mean and covariance was also done to obtain error
estimates. Group speeds for the inverted sound speed fields provide an excellent
match to the experimental data. The inverted sediment compressional speed profile
compares well with in situ measurements.
PMID- 11008802
TI - In situ estimation of sediment sound speed and critical angle
AB - Understanding the basic physics of sound penetration into ocean sediments is
essential for the design of sonar systems that can detect, localize, classify,
and identify buried objects. In this regard the sound speed of the sediment is a
crucial parameter as the ratio of sound speed at the water-sediment interface
determines the critical angle. Sediment sound speed is typically measured from
core samples using high frequency (100's of kHz) pulsed travel time measurements.
Earlier experimental work on subcritical penetration into sandy sediments has
suggested that the effective sound speed in the 2-20 kHz range is significantly
lower than the core measurement results. Simulations using Biot theory for
propagation in porous media confirmed that sandy sediments may be highly
dispersive in the range 1-100 kHz for the type of sand in which the experiments
were performed. Here it is shown that a direct and robust estimate of the
critical angle, and therefore the sediment sound speed, at the lower frequencies
can be achieved by analyzing the grazing angle dependence of the phase delays
observed on a buried array. A parametric source with secondary frequencies in the
2-16 kHz range was directed toward a sandy bottom similar to the one investigated
in the earlier study. An array of 14 hydrophones was used to measure penetrated
field. The critical angle was estimated by analyzing the variations of signal
arrival times versus frequency, burial depth, and grazing angle. Matching the
results with classical transmission theory yielded a sound speed estimate in the
sand of 1626 m/s in the frequency range 2-5 kHz, again significantly lower the
1720 m/s estimated from the cores at 200 kHz. However, as described here, this
dispersion is consistent with the predictions of the Biot theory for this type of
sand.
PMID- 11008803
TI - Measurement technique for bottom scattering in shallow water
AB - Sonar performance predictions of reverberation in shallow water rely upon good
estimates of the bottom-scattering strength. However, little is understood about
bottom scattering in shallow water in the frequency range 400-4000 Hz,
particularly its dependency upon frequency and its relationship to the physical
properties of the seafloor. In order to address these issues, a new measurement
technique has been developed to probe the frequency and angular dependency of
bottom-scattering strength. The experimental technique is described which employs
either coherent or incoherent sources (lightbulbs). In addition, measurement and
modeling results for two diverse shallow water sites are presented. At one site,
the scattering appears to arise at or near the water-sediment interface. At the
other site, scattering from a 23-m sub-bottom horizon is clearly apparent in the
data at and below 1800 Hz. The fact that our measurement technique can directly
reveal the presence of sub-bottom scattering is a significant advance in the
development of methods to explore the physical mechanisms that control bottom
scattering.
PMID- 11008804
TI - Low-grazing-angle monostatic acoustic reverberation from rough and heterogeneous
seafloors
AB - Numerical wavefield modeling, based on time domain finite difference solutions to
the full elastic wave equation, is used to quantitatively predict the sensitivity
of monostatic backscatter to variations in geological properties of the seabed.
This article addresses the hypothesis that observed backscatter signals from the
seafloor are produced by a combination of seafloor (interface) and subseafloor
(volume) scattering from structures having variations at scale lengths comparable
to the wavelength of the insonifying acoustic field. Wavelength-scale seafloor
roughness and subseafloor volume heterogeneity parameters are defined using
stochastic spatial probability functions having Gaussian autocorrelations. The
range of the variations in these parameters is constrained to realistic values
based on estimates derived from seafloor bathymetry and other geologic data.
Modeling results show that backscattering from rough, basaltic (hard) bottoms, in
the absence of large-scale seafloor slope, is dominated by rough surface
scattering with little contribution from volume scattering. Contrary to this,
sediment (soft) bottoms with subseafloor volume heterogeneity, with or without
seafloor roughness, produce significant backscattering signals compared to a
homogeneous sediment bottom.
PMID- 11008805
TI - Resonant response of complex shell structures
AB - Resonances of shell structures play a prominent role in determining their
acoustic characteristics. Among the most important of such characteristics are
radiated noise, scattering, and self-noise levels. The nature of the structural
resonances, for example the number of modes within a particular frequency band or
the overall spatial dependence of the response, determines the importance of
these phenomena in various contexts and what steps may be taken to modify their
acoustic impact. In the past, knowledge of the resonant response of highly
idealized systems has been used to guide the development of quiet platforms. The
results of a scale model investigation of the effects of increased complexity on
the nature of the resonances of submerged shell structures are reported. Effects
presented here are flexural Bloch mode resonances, localized resonances resulting
from structural irregularity, and the effects of non-axisymmetry on these
phenomena. The implications of these results on acoustic design and the
development of systems is discussed.
PMID- 11008806
TI - Sensor scheme design for active structural acoustic control
AB - Efficient sensing schemes for the active reduction of sound radiation from plates
are presented based on error signals derived from spatially weighted plate
velocity or near-field pressure. The schemes result in near-optimal reductions as
compared to weighting procedures derived from eigenvector or singular vector
analysis of the radiation operator. Efficient control configurations are
suggested using a, possibly analog, front-end implementing a bank of spatial
weighting functions and a digital controller with a minimized number of input and
output channels. The performance of different weighting functions is compared, as
well as the performance of different frequency-dependent filtering functions.
Design rules are given for the sensor spacing, the number of weighting functions,
the number of actuators, and the corresponding controller dimensionality.
PMID- 11008807
TI - The vibration behavior of railway track at high frequencies under multiple
preloads and wheel interactions
AB - The track foundation is preloaded by multiple wheel loads due to the train weight
and, as the pad and ballast are nonlinear, their stiffness depends upon the
preload in them. Due to the influence of these resilient components of the track,
the track vibration is affected by the wheel loads. It is also affected by the
wheel/rail interactions. In this article the preloads in the pad and ballast are
calculated by considering the nonlinear properties of the track foundation, and
thus the preloaded pad and ballast stiffnesses are determined. The vibration
properties are explored for the track under multiple wheel loads and multiple
wheel/rail interactions by comparing the results from different track models with
and without these effects. It is found that the point receptance of the track is
reduced and the vibration decay rate is enhanced at low frequencies due to the
wheel loads. The effects of the wheel/rail interactions are most significant for
frequencies 400-2000 Hz. Because of the wheel/rail interactions, the point
receptance fluctuates and the vibration decay is enhanced in the regions around
the wheels.
PMID- 11008808
TI - European methodology for testing the airborne sound insulation characteristics of
noise barriers in situ: experimental verification and comparison with laboratory
data
AB - In the frame of the 1994-1997 Standard, Measurement and Testing program, the
European Commission funded a research project, named Adrienne, to define new test
methods for measuring the intrinsic characteristics of road traffic noise
reducing devices in situ. The research team produced innovative methods for
testing the sound reflection/absorption and the airborne sound insulation
characteristics of noise barriers. These methods are now under consideration at
CEN (European Committee for Standardization), to become European standards. The
present work reports a detailed verification of the test method for airborne
sound insulation over a selection of 17 noise barriers, representative of the
Italian and European production. The samples were tested both outdoors, using the
new Adrienne method, and in laboratory, following the European standard EN 1793
2. In both cases the single number rating for airborne sound insulation
recommended by the European standard was calculated. The new method proved to be
easy to use and reliable for all kinds of barriers. It has been found sensitive
to quality of mounting, presence of seals, and other details typical of outdoor
installations. The comparison between field and laboratory results shows a good
correlation, while existing differences can be explained with the different sound
fields and mounting conditions between the outdoor and laboratory tests. It is
concluded that the Adrienne method is adequate for its intended use.
PMID- 11008809
TI - The effect of high-amplitude sound on the attenuation of perforated tube
silencers
AB - A time-domain computational approach is applied to investigate the behavior of
perforated tube silencers at high sound levels. The one-dimensional computational
technique employs a lumped parameter model for the perforate flows. The lumped
parameter perforate model is based on time-invariant approximations for the
equivalent length l(eq) and resistance R, consistent with the use of a nonlinear
perforate impedance. Empirical expressions for l(eq) and R are developed
experimentally using nondimensional scaling parameters. The model is applied to
geometries representative of automotive resonators and multiple-duct mufflers.
Conditions are simplified from those in an actual automotive system by
considering single-frequency excitation and zero mean flow. Simulations with
linear perforate behavior are compared to experimental data obtained with an
extended impedance tube system. Simulations with nonlinear perforate behavior for
one concentric tube resonator are compared to published experimental data.
PMID- 11008810
TI - Interference from degraded auditory stimuli: linear effects of changing-state in
the irrelevant sequence.
AB - Cognitive performance, particularly on a number of tasks involving short-term
memory for order, is impaired by the mere presence of irrelevant background
sound. The current study examines the features of the irrelevant sound that
determine its disruptive potency. Previous research suggests that the amount of
variability in an irrelevant stream is related to the degree of disruption of
memory. The present experiments used a parametric approach to manipulate degree
of change more precisely. Increasing levels of degradation, effected either by
low-pass filtering (speech) or by digital manipulation (speech and nonspeech),
monotonically decreased the degree of interference. The findings support the
following propositions: (i) the degree of physical change within an auditory
stream is the primary determinant of the degree of disruption; and, (ii) the
effects of irrelevant speech and irrelevant nonspeech sounds are functionally
similar.
PMID- 11008811
TI - Acoustic optic hybrid (AOH) sensor
AB - The ability of laser vibrometers to receive and process acoustic echoes from the
water surface above a submerged target is established and evaluated. Sonar echoes
from a submerged target are collected from the water surface by a laser
vibrometer. Feasibility of this approach to sensing underwater sound is
demonstrated. If the acoustic excitation at an otherwise undisturbed water
surface is 195 to 168 dB re: 1 microPa, signal-to-noise ratio (SNR), at the
vibrometer output, is shown to range from about 46 to 6 dB. Capillary waves and
gravity waves at the water surface are expected and shown to have some
destructive effect on the process of echo retrieval. A series of experiments to
quantify the surface wave effects is described. The wave experiment results are
reported. A successful attempt to acquire echoes from a submerged target over a
grid of points for further processing into a three-dimensional image is made and
described. The data acquisition and beamforming techniques constitute a three
dimensional, acoustic optic, synthetic aperture sonar (SAS). Beamformed images
are included. For an aircraft towing acoustic sensors through the water with a
mechanical link, this technique holds the promise of increased safety and
improved fuel efficiency.
PMID- 11008812
TI - Acoustic impedances at the oval window, and sound pressure transformation of the
middle ear in Norwegian cattle.
AB - In 15 cadaver ears from Norwegian cattle, sound pressure transfer functions have
been measured (1) for sound input to the tympanic membrane, (2) for sound input
to the oval window with the footplate in place, but with the ossicular chain
removed, and (3) for sound input to the oval window with also the footplate
removed. The output pressure was measured in an enclosure cemented to the round
window. The data allow calculation of equivalent sound pressures at the input
positions, as well as the acoustic input impedances at the oval window with
intact footplate, Z(sc), and with the footplate removed, Z(c). The difference
Z(s)=Z(sc)-Z(c) is the acoustic impedance contribution of the footplate and
annular ligament. Z(sc) is mainly determined by the stiffness of the annular
ligament at low frequencies, and by the cochlear input impedance Z(c) at higher
frequencies. Z(c) is predominately resistive, a minor reactive part at low
frequencies is attributed to the stiffness of the round window membrane. Z(s) and
Z(c) are equal in magnitude at about 0.4 kHz. Rather close RLC fits have been
obtained for all the three impedances, Z(sc), Z(s), and Z(c). The fitted values
for the resistive parts of Z(sc) and Z(c) are 62.9 and 58.2 acoustic Gomega,
respectively. The relatively small difference, 4.7 Gomega, is attributed to the
resistance of the annular ligament. The fitted resistance of Z(s) is somewhat
larger, 8.6 Gomega, but is anyway of minor importance relative to the dynamic
stiffness of the annular ligament. This stiffness depends on the static pressure
difference across the footplate. Each of the averaged Z(sc) corresponds to
minimum stiffness. The fitted acoustic compliance is 6.89 x 10(-15) m3/Pa. The
acoustic inertance plays a minor role. It is attributed to the mass of the
footplate and the co-vibrating liquid in the inner ear, and has a fitted value of
4.7 x 10(5) Pa s2/m3. A sound pressure at the eardrum is equivalent to a larger
pressure at the footplate, about 16 dB larger at frequencies below 100 Hz,
increasing to about 30 dB at 10 kHz. In the vestibulum at the inner side of the
footplate, the sound pressure at 20 Hz is about 20 dB below the equivalent
pressure at the outer side. The two pressures approach toward higher frequencies,
and above 1 kHz they are nearly equal.
PMID- 11008813
TI - An automated procedure for identifying spontaneous otoacoustic emissions.
AB - An algorithm is described for objectively identifying and measuring spontaneous
otoacoustic emissions (SOAEs) using the spectrum that results from transformation
of the acoustic waveform measured in the outer ear canal. Prior to spectral
analysis, the rms level is calculated for successive short segments of the
waveform and only the weakest 25% of the segments are retained for the spectral
analysis [the quietest 150 when using 16k-point fast Fourier transforms (FFTs)].
The resulting initial spectrum is scanned for peaks (potential SOAEs) which are
then deleted from the spectrum. New values are estimated for the deleted values
using linear extrapolations from frequency ranges on either side of the deleted
values. The end result is a smoothed spectrum devoid of all local peaks. The
initial spectrum is then compared peak-by-peak with the smoothed spectrum, and
those peaks having differences that exceed an objectively determined decision
criterion are identified as likely SOAEs. The effects of varying some of the
important parameter values of the algorithm are described, and the sensitivity of
the procedure is evaluated by measuring the detection rate for a Lorentzian peak
of known amplitude added to a spectrum otherwise devoid of SOAEs.
PMID- 11008814
TI - On the spectral periodicity of transient-evoked otoacoustic emissions from normal
and damaged cochleas.
AB - The spectral quasi-periodicity of transient-evoked otoacoustic emissions (TEOAE)
is well acknowledged since Zwicker described a preferred spacing of 0.4 bark
between consecutive peaks in the spectrum of otoacoustic emissions from normal
ears. While there is scarce evidence of any anatomical reason for this
regularity, several functional models of the cochlea have predicted that the
structure of emission spectra reflects important characteristics of cochlear
filters. In an attempt to check such predictions, the average regularity of TEOAE
spectra was studied in three groups of human subjects, normally hearing adults,
healthy neonates, and adults suffering from noise-induced hearing loss.
Significant differences in emission periodicities were found. Around 1 kHz, the
preferred spacing was close to 130 Hz in normally hearing adult ears and
neonates. In contrast, no clear periodicity was found in the group of damaged
ears, even though they had clinically normal pure-tone audiometry below 2 kHz.
Around 4 kHz, the preferred spacing was close to 240 Hz in normal adults and
neonates, whereas TEOAEs were absent in many impaired ears. A phenomenological
model assuming that TEOAEs stem from the responses of a slightly disarrayed bank
of highly tuned filters predicts that the filter width would be the same in
healthy young adults and neonates. In contrast, ears suffering from high
frequency hearing loss could exhibit early damaged filters. The proposed method
might provide an objective assessment of parameters otherwise difficult to
evaluate, especially in neonatal cochleas.
PMID- 11008815
TI - A noninvasive method for estimating acoustic admittance at the tympanic membrane.
AB - The acoustic admittance at the tympanic membrane (TM), Y(TM), describes the
linear acoustic properties of the ear. Here, a noninvasive measurement procedure
is developed for estimating Y(TM) in intact ears. The method consists of (1)
measuring the admittance in the ear canal Y(EC) with a commercially available
earphone-and-microphone system, and (2) estimating Y(TM) via a uniform-tube
approximation of the space between the measurement point and the TM. The
dimensions of this space are estimated from Y(EC) via an area-estimation
algorithm [Keefe et al., J. Acoust. Soc. Am. 91, 470 (1992)] and measurements
made with controlled static pressures in the canal. Measurements in artificial
loads are used to test the accuracy of the measurement system and to determine
sources of error. For accurate admittance measurements: (1) extension of the
microphone tube medially beyond the earphone's port is necessary for frequencies
above 2 kHz; (2) the acoustic system must be calibrated in known loads with
diameters within 15% of the canal diameter, because the source's output
characteristics vary with load diameter. The method is applied to intact ears of
anesthetized domestic cats; for frequencies below 5 kHz, the estimated Y(TM) in
four ears have features that are similar to those of previous measurements made
at the cat TM. Sources of error include nonuniform waves generated at the
earphone's narrow port, inaccuracy in estimation of canal dimensions, irregular
geometry of the canal, and earphone-microphone cross talk.
PMID- 11008816
TI - Tests of some common assumptions of ear-canal acoustics in cats.
AB - The accuracy of ear-canal admittance and reflectance as measures of the ear's
properties depends on the acoustic effects of the canal. Here, measurements of
acoustic admittance at different canal locations in domestic cats are used to
test three common assumptions. (1) Can a uniform-tube model of the canal
represent spatial variations in admittance? Data from cats support this
assumption for frequencies below 3 kHz, where the admittance inferred at the
tympanic membrane (TM) based on a uniform-tube model differs by less than 3 dB in
magnitude and 0.07 periods in angle from the admittance measured at the TM; for
higher frequencies greater differences occur. (2) Do large static air pressures
in the canal make the middle ear rigid without affecting the properties of the
canal space? The measurements reported indicate that large negative static
pressures reduce the low-frequency compliance of the cat middle ear to about 10%
of the compliance of the canal air volume. Static displacements of the acoustic
probe, TM, and canal walls with static pressure may affect estimates of the canal
volume and middle-ear compliance by as much as 15% to 20%. (3) Is the acoustic
reflectance magnitude constant with position along the canal? Reflectance data
from cat ear canals generally support this idea, except within a frequency region
near 0.5 kHz for which there is evidence of energy loss. These results
demonstrate that noninvasive measurements in the canal describe middle-ear
acoustic properties to within tolerances that depend on the effects of the canal.
PMID- 11008817
TI - Perceived continuity and pitch perception.
AB - Three experiments investigated the importance of perceived stimulus continuity
for the perception of the fundamental frequency (F0) of an unresolved complex
tone. The F0 of the complex was 250 Hz and the harmonics were bandpass filtered
between 5500 and 7500 Hz. In the first experiment, F0 discrimination was measured
for single-burst tones with durations of 20, 40, and 80 ms, and for stimuli
containing two 20- or 40-ms tone bursts separated by an 8- or 16-ms gap. For the
single-burst conditions, there was a large decrease in threshold as the duration
was increased from 20 to 40 ms. However, performance in the gapped conditions was
much worse than that for the single-burst condition with the same cumulative
duration (e.g., two 20-ms bursts separated by 8 ms produced higher thresholds
than one 40-ms burst). Adding a bandpass noise (with the same spectral envelope
as the tone) in the gap between the two tone bursts improved performance to the
level of the single-burst condition. When the noise was added, the two discrete
tone bursts were perceived as one single tone burst interrupted by the noise, and
this seemed to facilitate discrimination. In a second experiment, the effects on
pitch of an envelope delay (phase shift) of 0.75 periods between two tone bursts
separated by an 8-ms gap were investigated. If the gap was silent, the pitch of
the pair was unaffected by the phase shift. However, if the gap contained the
bandpass noise, the phase shift between the bursts did produce a significant
downward shift in the pitch of the pair. Finally, the third experiment showed
that presenting a noise before a single 20-ms burst may improve discrimination
performance in some listeners, but not sufficiently to account for the results of
the first experiment purely in terms of an improvement in the discriminability of
the second tone burst in the pair. The experiments suggest that a level decrease
between two tone bursts may disrupt or reset a long integration mechanism,
decreasing performance. When there is no level decrease between the bursts, the
auditory system may assume that the two bursts belong to the same single tone and
analyze them together in order to derive F0.
PMID- 11008818
TI - The lower limit of pitch as determined by rate discrimination.
AB - This paper is concerned with the lower limit of pitch for complex, harmonic
sounds, like the notes produced by low-pitched musical instruments. The lower
limit of pitch is investigated by measuring rate discrimination thresholds for
harmonic tones filtered into 1.2-kHz-wide bands with a lower cutoff frequency,
F(c), ranging from 0.2 to 6.4 kHz. When F(c) is below 1 kHz and the harmonics are
in cosine phase, rate discrimination threshold exhibits a rapid, tenfold decrease
as the repetition rate is increased from 16 to 64 Hz, and over this range, the
perceptual quality of the stimuli changes from flutter to pitch. When F(c) is
increased above 1 kHz, the slope of the transition from high to low thresholds
becomes shallower and occurs at progressively higher rates. A quantitative
comparison of the cosine-phase thresholds with subjective estimates of the
existence region of pitch from the literature shows that the transition in rate
discrimination occurs at approximately the same rate as the lower limit of pitch.
The rate discrimination experiment was then repeated with alternating-phase
harmonic tones whose envelopes repeat at twice the repetition rate of the
waveform. In this case, when F(c) is below 1 kHz, the transition in rate
discrimination is shifted downward by almost an octave relative to the transition
in the cosine-phase thresholds. The results support the hypothesis that in the
low-frequency region, the pitch limit is determined by a temporal mechanism,
which analyzes time intervals between peaks in the neural activity pattern. It
seems that temporal processing of pitch is limited to time intervals less than 33
ms, corresponding to a pitch limit of about 30 Hz.
PMID- 11008819
TI - Characterizing frequency selectivity for envelope fluctuations.
AB - Three experimental paradigms were used to specify the auditory system's frequency
selectivity for amplitude modulation (AM). In the first experiment, masked
threshold patterns were obtained for signal-modulation frequencies of 4, 16, 64,
and 256 Hz in the presence of a half-octave-wide modulation masker, both applied
to the same noise carrier with a bandwidth ranging from 1 to 4 kHz. In the second
experiment, psychophysical tuning curves (PTCs) were obtained for signal
modulation frequencies of 16 and 64 Hz imposed on a noise carrier as in the first
experiment. In the third experiment, masked thresholds for signal-modulation
frequencies of 8, 16, 32, and 64 Hz were obtained according to the "classical"
band-widening paradigm, where the bandwidth of the modulation masker ranged from
1/8 to 4 octaves, geometrically centered on the signal frequency. The first two
experiments allowed a direct derivation of the shape of the modulation filters
while the latter paradigm only provided an indirect estimate of the filter
bandwidth. Thresholds from the experiments were predicted on the basis of an
envelope power-spectrum model (EPSM) which integrates the envelope power of the
modulation masker in the passband of a modulation filter tuned to the signal
modulation frequency. The Q-value of second-order bandpass modulation filters was
fitted to the masking patterns from the first experiment using a least-squares
algorithm. Q-values of about 1 for frequencies up to 64 Hz suggest an even weaker
selectivity for modulation than assumed in earlier studies. The same model also
accounted reasonably well for the shape of the temporal modulation transfer
function (TMTF) obtained for carrier bandwidths in the range from 1 to 6000 Hz.
Peripheral filtering and effects of peripheral compression were also investigated
using a multi-channel version of the model. Waveform compression did not
influence the simulated results. Peripheral bandpass filtering only influenced
thresholds for high modulation frequencies when signal information was strongly
attenuated by the transfer function of the peripheral filters.
PMID- 11008820
TI - The use of visible speech cues for improving auditory detection of spoken
sentences.
AB - Classic accounts of the benefits of speechreading to speech recognition treat
auditory and visual channels as independent sources of information that are
integrated fairly early in the speech perception process. The primary question
addressed in this study was whether visible movements of the speech articulators
could be used to improve the detection of speech in noise, thus demonstrating an
influence of speechreading on the ability to detect, rather than recognize,
speech. In the first experiment, ten normal-hearing subjects detected the
presence of three known spoken sentences in noise under three conditions:
auditory-only (A), auditory plus speechreading with a visually matched sentence
(AV(M)) and auditory plus speechreading with a visually unmatched sentence
(AV(UM). When the speechread sentence matched the target sentence, average
detection thresholds improved by about 1.6 dB relative to the auditory condition.
However, the amount of threshold reduction varied significantly for the three
target sentences (from 0.8 to 2.2 dB). There was no difference in detection
thresholds between the AV(UM) condition and the A condition. In a second
experiment, the effects of visually matched orthographic stimuli on detection
thresholds was examined for the same three target sentences in six subjects who
participated in the earlier experiment. When the orthographic stimuli were
presented just prior to each trial, average detection thresholds improved by
about 0.5 dB relative to the A condition. However, unlike the AV(M) condition,
the detection improvement due to orthography was not dependent on the target
sentence. Analyses of correlations between area of mouth opening and acoustic
envelopes derived from selected spectral regions of each sentence (corresponding
to the wide-band speech, and first, second, and third formant regions) suggested
that AV(M) threshold reduction may be determined by the degree of auditory-visual
temporal coherence, especially between the area of lip opening and the envelope
derived from mid- to high-frequency acoustic energy. Taken together, the data
(for these sentences at least) suggest that visual cues derived from the dynamic
movements of the fact during speech production interact with time-aligned
auditory cues to enhance sensitivity in auditory detection. The amount of visual
influence depends in part on the degree of correlation between acoustic envelopes
and visible movement of the articulators.
PMID- 11008821
TI - Effects of frequency and level on auditory stream segregation.
AB - This study examined the effect of center frequency and level on the perceptual
grouping of rapid tone sequences. The sequence ABA-ABA-...was used, where A and B
represent sinusoidal tone bursts (10-ms rise/fall, 80-ms steady state, 20-ms
interval between tones) and - represents a silent interval of 120 ms. In
experiment 1, tone A was fixed in frequency at 62, 125, 250, 500, 1000, 2000,
4000, 6000, or 8000 Hz. Both tones had a level of approximately 40 dB SL. Tone B
started with a frequency well above that of tone A, and its frequency was swept
toward that of tone A so that the frequency separation between them decreased in
an exponential manner. Subjects were required to indicate when they could no
longer hear the tones A and B as two separate streams, but heard only a single
stream with a "gallop" rhythm. This changeover point between percepts is called
the fission boundary. The separation between tones A and B at the fission
boundary was roughly independent of the frequency of tone A when expressed as the
difference in number of equivalent rectangular bandwidths (ERBs) between A and B,
but varied more with frequency when the difference was expressed in barks or
cents. In experiment 2, the center frequency was fixed at 250, 1000, or 4000 Hz,
and the level of the A and B tones was 40, 55, 70, or 85 dB SPL. The frequency
separation of the A and B tones at the fission boundary tended to increase
slightly with increasing level, in a manner consistent with the broadening of the
auditory filter with increasing level. The results support the "peripheral
channeling" explanation of stream segregation advanced by Hartmann and Johnson
[Music Percept. 9, 155-184 (1991)], and indicate that the perception of fusion or
fission in alternating-tone sequences depends partly upon the degree of overlap
of the excitation patterns evoked by the successive sounds in the cochlea, as
assumed in the theory of Beauvois and Meddis [J. Acoust. Soc. Am. 99, 2270-2280
(1996)].
PMID- 11008822
TI - Neural system identification model of human sound localization.
AB - This paper examines the role of biological constraints in the human auditory
localization process. A psychophysical and neural system modeling approach was
undertaken in which performance comparisons between competing models and a human
subject explore the relevant biologically plausible "realism constraints." The
directional acoustical cues, upon which sound localization is based, were derived
from the human subject's head-related transfer functions (HRTFs). Sound stimuli
were generated by convolving bandpass noise with the HRTFs and were presented to
both the subject and the model. The input stimuli to the model were processed
using the Auditory Image Model of cochlear processing. The cochlear data were
then analyzed by a time-delay neural network which integrated temporal and
spectral information to determine the spatial location of the sound source. The
combined cochlear model and neural network provided a system model of the sound
localization process. Aspects of humanlike localization performance were
qualitatively achieved for broadband and bandpass stimuli when the model
architecture incorporated frequency division (i.e., the progressive integration
of information across the different frequency channels) and was trained using
variable bandwidth and center-frequency sounds. Results indicate that both issues
are relevant to human sound localization performance.
PMID- 11008823
TI - Complex tactile waveform discrimination.
AB - Complex vibrotactile waveforms consisting of two superimposed sinusoids at
varying phases were presented to the fingertip, and observers made "same
different" judgments. It was found that the low-frequency (10Hz+30Hz) waveforms
were discriminable from one another while discrimination of the high-frequency
(100Hz+300Hz) vibrations was poor. High-frequency adaptation did not impair
discrimination of the low-frequency waveforms, suggesting that the RA channel
mediated discrimination. Low-frequency adaptation impaired discrimination of the
high-frequency stimuli, suggesting that the RA channel likewise mediated the
modest level of performance observed in the absence of an adapting stimulus. The
results indicate that this channel encodes complex waveforms temporally. A simple
model for low-frequency waveform discrimination is proposed. The results obtained
with the high-frequency complex waveforms are compatible with the hypothesis that
the PC channel integrates stimulus energy over time.
PMID- 11008824
TI - Perceptual calibration of F0 production: evidence from feedback perturbation.
AB - Hearing one's own speech is important for language learning and maintenance of
accurate articulation. For example, people with postlinguistically acquired
deafness often show a gradual deterioration of many aspects of speech production.
In this manuscript, data are presented that address the role played by acoustic
feedback in the control of voice fundamental frequency (F0). Eighteen subjects
produced vowels under a control (normal F0 feedback) and two experimental
conditions: F0 shifted up and F0 shifted down. In each experimental condition
subjects produced vowels during a training period in which their F0 was slowly
shifted without their awareness. Following this exposure to transformed F0, their
acoustic feedback was returned to normal. Two effects were observed. Subjects
compensated for the change in F0 and showed negative aftereffects. When F0
feedback was returned to normal, the subjects modified their produced F0 in the
opposite direction to the shift. The results suggest that fundamental frequency
is controlled using auditory feedback and with reference to an internal pitch
representation. This is consistent with current work on internal models of speech
motor control.
PMID- 11008825
TI - Acoustic characteristics of English fricatives.
AB - This study constitutes a large-scale comparative analysis of acoustic cues for
classification of place of articulation in fricatives. To date, no single metric
has been found to classify fricative place of articulation with a high degree of
accuracy. This study presents spectral, amplitudinal, and temporal measurements
that involve both static properties (spectral peak location, spectral moments,
noise duration, normalized amplitude, and F2 onset frequency) and dynamic
properties (relative amplitude and locus equations). While all cues (except locus
equations) consistently serve to distinguish sibilant from nonsibilant
fricatives, the present results indicate that spectral peak location, spectral
moments, and both normalized and relative amplitude serve to distinguish all four
places of fricative articulation. These findings suggest that these static and
dynamic acoustic properties can provide robust and unique information about all
four places of articulation, despite variation in speaker, vowel context, and
voicing.
PMID- 11008826
TI - Intelligibility of bandpass speech: effects of truncation or removal of
transition bands.
AB - An intelligibility of over 90% was reported for keywords in "everyday" 1/3-octave
sentences centered on 1500 Hz and having steep transition band slopes of 100
dB/octave [Warren et al., Percept. Psychophys. 57, 175-182 (1995)]. A subsequent
study by Warren and Bashford [J. Acoust. Soc. Am. 106, L47-L52 (1999)] found that
it was not the 1/3-octave passband, but the transition bands that were chiefly
responsible for this high intelligibility: When the passband and transition bands
were segregated using filter slopes of 1000 dB/octave, the isolated passband had
an intelligibility score of only 24%, while the pair of transition bands had a
score of over 80%. In the present study, experiment 1 examined the distribution
of information along the transition bands' slopes by truncation at graded
downpoints: Truncation at downpoints of 40 dB or more produced no significant
change in intelligibility. Experiment 2 closed the gap separating the transition
bands so that their slopes intersected at 1500 Hz. This triangular band had a
negligible passband (as defined conventionally by 3-dB downpoints) and an
intelligibility score of 60%; truncation at downpoints of 50 dB or more produced
no significant change in intelligibility. Experiment 3 determined the
intelligibilities of rectangular bands (1000-dB/octave slopes) centered on 1500
Hz. Their bandwidths ranged from 3 to 12 semitones in 1-semitone steps, resulting
in intelligibility scores increasing monotonically from 14% to 94%. Calculations
based upon experiments 2 and 3 showed that the triangular band truncated at 30-dB
downpoints had half the intelligibility of a rectangular band having the same
frequency range.
PMID- 11008827
TI - The relationship between speech perception and electrode discrimination in
cochlear implantees.
AB - Speech Intelligibility Index (SII) procedures were used to measure the amount of
speech information perceived in five frequency bands (170-570, 570-1170, 1170
1768, 1768-2680, and 2680-5744 Hz) by 15 users of the Cochlear Ltd. CI-22M
implant and Spectra-22/SPEAK processor. The speech information perceived was
compared to that perceived by normal-hearing listeners. The ability of these
subjects to discriminate between stimulation on adjacent electrodes corresponding
to each frequency band was also investigated, using a 4IFC procedure with random
current level variations of between 0% and 60% of the dynamic range. Relative to
normal-hearing listeners, speech information was, on average, significantly more
reduced in the four frequency regions between 170 and 2680 Hz than in the region
2680-5744 Hz. There was a significant correlation between electrode
discrimination ability (when the random level variation encompassed 20% or more
of the dynamic range) and the amount of speech information perceived in the four
frequency regions between 170 and 2680 Hz. There was no such correlation in the
region 2680-5744 Hz, regardless of the extent of random level variation. These
results indicate that speech information in the low to medium frequencies is more
difficult for implantees to perceive, that this difficulty is correlated with the
difficulty in discriminating electrode place in the presence of random loudness
variations, and that fine spectral discrimination may be relatively more
important in the vowel-formant regions than in higher frequency regions.
PMID- 11008828
TI - In vitro measurement of the frequency-dependent attenuation in cancellous bone
between 0.2 and 2 MHz.
AB - Our goal was to evaluate the frequency dependence of the ultrasonic attenuation
coefficient in cancellous bone. Estimates were obtained in immersion, using a
substitution method in the through-transmit mode, by scanning 14 human bone
specimens (calcaneus). Measurements were performed with three pairs of focused
transducers with a center frequency of 0.5, 1.0, and 2.25 MHz, respectively in
order to cover an extended frequency bandwidth (0.2-1.7 MHz). When the
experimental attenuation coefficient values were modeled with a nonlinear power
fit alpha(f)=alpha0 +alpha(I)f(n), the attenuation coefficient was found to
increase as f(1.09+/-0.3) over the measurement bandwidth. However, a substantial
variation of the exponent n (0.4-2.2) within specimens and also between specimens
was observed. The acoustical parameters were compared to bone mineral density. A
highly significant relationship was noted between alpha1 and BMD (r2= 0.75, p<
10(-4)). No correlation was found between n and BMD. Several attenuation
mechanisms are discussed as well as the potential impact these results may have
in in vivo quantitative measurements.
PMID- 11008829
TI - Ultrasound-induced lung hemorrhage is not caused by inertial cavitation.
AB - In animal experiments, the pathogenesis of lung hemorrhage due to exposure to
clinical diagnostic levels of ultrasound has been attributed to an inertial
cavitation mechanism. The purpose of this article is to report the results of two
experiments that directly contradict the hypothesis that ultrasound-induced lung
hemorrhage is caused by inertial cavitation. Elevated hydrostatic pressure was
used to suppress the involvement of inertial cavitation. In experiment one, 160
adult mice were equally divided into two hydrostatic pressure groups (0.1 or 1.1
MPa), and were randomly exposed to pulsed ultrasound (2.8-MHz center frequency, 1
kHz PRF, 1.42-micros pulse duration, 10-s exposure duration). For the two
hydrostatic pressure groups (80 mice each), 8 in situ peak rarefactional pressure
levels were used that ranged between 2.82 and 11.8 MPa (10 mice/group). No effect
of hydrostatic pressure on the probability of hemorrhage was observed. These data
lead to the conclusion that lung hemorrhage is not caused by inertial cavitation.
Also, the higher hydrostatic pressure enhanced rather than inhibited the impact
of ultrasonic pressure on the severity (hemorrhage area, depth, and volume) of
lesions. These counterintuitive findings were confirmed in a second experiment
using a 2 x 5 factorial design that consisted of two ultrasonic pressure levels
and five hydrostatic pressure levels (100 mice, 10 mice/group). If inertial
cavitation were the mechanism responsible for lung hemorrhage, then elevated
hydrostatic pressures should have resulted in less rather than more tissue damage
at each ultrasonic pressure level. This further supports the conclusion that the
pathogenesis of ultrasound-induced lung hemorrhage is not caused by inertial
cavitation.
PMID- 11008830
TI - Acoustic flow perception in cf-bats: extraction of parameters.
AB - The narrow-band portions of the echolocation pulses seen in cf-bats are a
hypothetical substrate for target localization. This localization could be based
on estimates of echo envelope amplitude and carrier frequency together with their
derivatives. Evaluation of these parameters is referred to as "acoustic flow" in
loose analogy to optic flow. It is assessed whether the requirements for this
task may be reconciled with known principles of auditory function. For the
evaluation of a single echo, this seems to be the case: auditory filter shapes
provide sufficient frequency resolution; at the same time envelopes are preserved
well and some noise removal is achieved. Nevertheless, should bats not be endowed
with additional capabilities for noise removal, analysis of acoustic flow would
be limited to favorable signal-to-noise ratios. Multiple, temporally overlapping
echoes are probable in any realistic echolocation scenario. In this case,
additional auditory processing steps have to be postulated, which allow
simultaneous estimation of multiple carrier frequencies and reduction of
demodulation distortions.
PMID- 11008831
TI - A mathematical analysis of the peripheral auditory system mechanics in the
goldfish (Carassius auratus).
AB - The dynamic response of the goldfish peripheral auditory system has been analyzed
using lumped-parameter mechanical and fluid system models for the swimbladder,
Weberian apparatus, and saccule. The swimbladder is treated as a two degree-of
freedom mechanical system consisting of two coupled mass-spring-damper
arrangements. The swimbladder is coupled to the Weberian ossicles using a
phenomenological analysis of the anterior swimbladder tunica externa which
permits both stretching and sliding. Analysis of the saccule features only a
single degree of freedom, corresponding to the direction of orientation of the
ciliary bundles. Inputs to the saccule consist of the transverse canal fluid
motion and the motion of the animal's head (assumed to match the local acoustic
particle motion). Mechanical properties required for the system equations were
estimated from published literature, direct measurements, and curve fits to
experimental data for the motions of the swimbladders. The results indicate that
the Weberian apparatus has a significant impact on hearing ability over the
entire auditory bandwidth, not just at higher frequencies, and that the saccule
functions as a displacement sensor above approximately 300 Hz.
PMID- 11008833
TI - A software model to estimate zones of impact on marine mammals around
anthropogenic noise.
AB - Anthropogenic noise impacts marine mammals in a variety of ways. In order to
estimate over which ranges this happens, we first need to understand the
propagation of noise through the ocean away from the noise source, and, second,
understand the relationship between received noise levels and impact thresholds.
A software package combining both aspects is presented. (1) A sound propagation
model based on ray theory was developed to calculate received noise levels as a
function of range, depth, and frequency. (2) Current knowledge of noise impact
thresholds for marine mammals was gathered and included in software routines
predicting zones of impact on marine mammals around industrial underwater noise
sources. As input parameters, this software package requires the source level and
spectrum of the noise of interest; physical oceanography data about the local
ocean environment such as bathymetry, bottom and surface loss data, and sound
speed profiles; and bioacoustical information about the target species in the
form of an audiogram, critical auditory bandwidths, spectra of typical animal
vocalizations, reported sound levels of disturbance, and criteria for hearing
damage. As output, the software produces data files and plots of the zones of
audibility, masking, disturbance, and potential hearing damage around a noise
source.
PMID- 11008832
TI - Masking in three pinnipeds: underwater, low-frequency critical ratios.
AB - Behavioral techniques were used to determine underwater masked hearing thresholds
for a northern elephant seal (Mirounga angustirostris), a harbor seal (Phoca
vitulina), and a California sea lion (Zalophus californianus). Octave-band white
noise maskers were centered at five test frequencies ranging from 200 to 2500 Hz;
a slightly wider noise band was used for testing at 100 Hz. Critical ratios were
calculated at one masking noise level for each test frequency. Above 200 Hz,
critical ratios increased with frequency. This pattern is similar to that
observed in most animals tested, and indicates that these pinnipeds lack
specializations for detecting low-frequency tonal sounds in noise. However, the
individual pinnipeds in this study, particularly the northern elephant seal,
detected signals at relatively low signal-to-noise ratios. These results provide
a means of estimating zones of auditory masking for pinnipeds exposed to
anthropogenic noise sources.
PMID- 11008834
TI - Zones of impact around icebreakers affecting beluga whales in the Beaufort Sea.
AB - A software model estimating zones of impact on marine mammals around man-made
noise [C. Erbe and D. M. Farmer, J. Acoust. Soc. Am. 108, 1327-1331 (2000)] is
applied to the case of icebreakers affecting beluga whales in the Beaufort Sea.
Two types of noise emitted by the Canadian Coast Guard icebreaker Henry Larsen
are analyzed: bubbler system noise and propeller cavitation noise. Effects on
beluga whales are modeled both in a deep-water environment and a near-shore
environment. The model estimates that the Henry Larsen is audible to beluga
whales over ranges of 35-78 km, depending on location. The zone of behavioral
disturbance is only slightly smaller. Masking of beluga communication signals is
predicted within 14-71-km range. Temporary hearing damage can occur if a beluga
stays within 1-4 km of the Henry Larsen for at least 20 min. Bubbler noise
impacts over the short ranges quoted; propeller cavitation noise accounts for all
the long-range effects. Serious problems can arise in heavily industrialized
areas where animals are exposed to ongoing noise and where anthropogenic noise
from a variety of sources adds up.
PMID- 11008835
TI - Application of a multiple-beam model for lateral vibration analysis of a
discretely supported rail at high frequencies
AB - In this paper a multiple-beam model of the rail, which allows all the essential
deformations caused by the lateral vibration, has been applied for studying the
lateral vibration behavior related to the discrete supports. Detailed
investigation of the lateral vibration of a discretely supported rail has been
carried out using a Green's function matrix and the superposition principle. Good
agreement between the predictions and measurement data has been reached in terms
of accelerance.
PMID- 11008836
TI - Active control design for acoustic radiation using mixed-norm optimization
AB - Linear matrix inequalities were applied to design a mixed H2/H(infinity) feedback
control compensator for a structural acoustic system. The compensator was
designed to minimize the H2 norm of radiation filters while constraining the
H(infinity) norm through the control path to be less than unity. A trade-off
between minimizing sound power radiated and maximum rms gain in the control path
resulted in a reliable and robust means of designing compensators for structural
acoustic control.
PMID- 11008837
TI - Finding the right cross-correlation peak for locating sounds in multipath
environments with a fourth-moment function
AB - To locate calling animals in reverberant environments from recordings on widely
separated receivers, a fourth-moment "Augmented-Template Correlation Function"
(ATCF) helps identify which of many peaks in each cross-correlation function is
that corresponding to the difference in travel times for the first arrivals
(reference-lag). This peak may not be the largest. The ATCF, by providing an
approximate correlation between auto- and cross-correlation functions, can be
orders of magnitude more efficient in selecting the reference-lag than the
alternative of randomly selecting peaks. The ATCF's efficacy increases with the
number of paths and their signal-to-noise ratios.
PMID- 11008838
TI - A method for individual identification of echolocation signals in free-ranging
finless porpoises carrying data loggers.
AB - Echolocation click events of a free-ranging juvenile and an adult finless
porpoise (Neophocaena phocaenoides) were recorded with an acoustic data logger.
Additionally, dive depth and swim speed of the juvenile were recorded with a
behavior data logger. Echoes of echolocation signals from the water surface were
clearly detected in shallow dives approximately less than 2 m. The delay time
between a surface echo and a direct signal corresponded with the two-way
transmission time for the animal's depth, indicating that the signals originated
from the animal wearing the data loggers. The finless porpoises produced
echolocation signals frequently and were thought to be able to detect their depth
by listening to echoes from the water surface.
PMID- 11008839
TI - Introduction: the happiness in all our lives.
PMID- 11008840
TI - The measurement of happiness.
AB - Happiness has been defined either as a broad notion of how one feels about their
life in general or as an emotional or affective state. Depending on the way
researchers define the concept, there have been variable attempts at measurement.
With decades of research, we have a better understanding of how to measure the
happiness of others. A combination of quantitative and qualitative methods
appears to be most productive. If we assume that individuals with disabilities
are made happy in the same way as are people without disabilities, then we have a
good idea of how to proceed with practical and policy matters.
PMID- 11008841
TI - On the continuous calibration of happiness.
AB - The nature of happiness is considered. A model is reviewed in which the affect
system is continuously recalibrated regarding a given domain of experiences as a
function of the dominant affective tone those experiences have over time. In this
view, people who experience repeated negative affect in a domain undergo an
adjustment such that they become less demanding about the quality of experience
producing happiness; people who experience repeated positive affect in a domain
undergo an adjustment such that they become more demanding about the quality of
experience required for happiness. Each results in a re-balancing of the system.
As objective circumstances vary, the person still experiences both happiness and
unhappiness. Implications are considered for large life changes and for
individuals with disabilities.
PMID- 11008842
TI - From function to felicitude: physical disability and the search for happiness in
health services research.
AB - Historically, research and practice in physical disability have emphasized the
destructive and disabling consequences of illness and injury. More recently, we
have begun to measure outcomes related to health, satisfaction, and quality-of
life. There has been little systematic attention to the study of happiness,
felicitude, but data show that even for many of the people with most notable
impairment, levels of happiness are high. The quest for felicitude requires
methodological changes and, more significantly, greater professional humility to
appreciate that people with both physical and intellectual impairments are able
to experience and articulate their own satisfaction, pleasure, and joy. Fortified
with this unpretentiousness, we can find happiness and begin to incorporate it as
an outcome of clinical and public health programs.
PMID- 11008843
TI - Happiness as a treatment goal.
AB - Happiness is a concept reflecting general satisfaction with one's life and with
oneself, not necessarily congruent with objective indicators. A most important
ingredient is a positive self-image, depending, in turn, on positive perception
of self as compared to one's peers and to the expectations of important figures
in one's life. This requires understanding of personal strengths and constructive
acceptance of limitations. Helping individuals develop subjective self
satisfaction should be the goal in any treatment program, achieved through direct
therapeutic interventions as well as environmental supports (e.g., provision of
opportunities for success). It is essential that service providers differentiate
between their own values, goals, and administrative requirements and the
individual's personal preferences and wishes.
PMID- 11008844
TI - Williams syndrome and happiness.
AB - Williams syndrome is a genetic disorder resulting in a variety of medical and
developmental features, one of which is a frequent outward presentation of
substantial happiness. In this paper we describe the unique expression of
happiness in people with Williams syndrome, with several anecdotes and a frame by
frame conversational analysis. We then discuss this happiness in the context of
other dimensions of the impact of Williams syndrome, especially anxiety. We
conclude with a discussion of the role of genetics in emotions.
PMID- 11008845
TI - Learning about happiness from persons with Down syndrome: feeling the sense of
joy and contentment.
AB - One well-known stereotype about persons with Down syndrome is that they are
relentlessly "happy." Although some individuals with Down syndrome seem to
possess an unusual personality aspect that calls out the best in others, this
aspect should be viewed as distinct from the traditional stereotype. Many people
with Down syndrome have shattered popular expectations of what they might
accomplish, society still has lowered expectations for them. In this paper I seek
to identify those characteristics that offer genuine and thoughtful joyfulness
among these individuals. Happiness is closely aligned with a sense of peace, well
being, and/or contentment. A more appropriate contention is the idea that a rare
and potent trait holds within it true enrichment and peace among individuals with
Down syndrome.
PMID- 11008846
TI - Strategic planning for employee happiness: a business goal for human service
organizations.
AB - Employee happiness can impact substantially on an organization's performance. It
can influence employee retention, absenteeism, and work performance. Because of
this importance, such happiness is inseparable from the real business of the
organization and should be considered a business goal. Implementation and
development of the strategic plan associated with this goal becomes the
responsibility of a highly placed project team that has as its mission ensuring
employee satisfaction. The strategic plan includes procedures that allow
management to listen effectively to employees, assessing and responding to their
values and needs. In this paper we discuss the workforce and environmental
characteristics that are involved planning for employee happiness and the steps
in creating an organizational culture in which this can become a business goal.
PMID- 11008847
TI - Increasing independent decision-making skills of women with mental retardation in
simulated interpersonal situations of abuse.
AB - The effectiveness of two decision-making training approaches in increasing
independent decision-making skills of 36 women with mild mental retardation in
response to hypothetical social interpersonal situations involving abuse was
evaluated. Participants were randomly assigned to a control or one of two
training conditions (a decision-making training approach that either addressed
both cognitive and motivational aspects of decision-making or included only
instruction on the cognitive aspect of decision-making). Although both approaches
were effective relative to a control condition, the combined cognitive and
motivational training approach was superior to the cognitive only training
approach. The superiority of this approach was also reflected on a verbally
presented generalization task requiring participants to respond to a decision
making situation involving abuse from their own perspective and on a locus of
control scale that measured perceptions of control.
PMID- 11008848
TI - Quantifying the process and outcomes of person-centered planning.
AB - Although person-centered planning is a popular approach in the field of
developmental disabilities, there has been little systematic assessment of its
process and outcomes. To measure person-centered planning, we developed three
instruments designed to assess its various aspects. We then constructed variables
comprising both a Process and an Outcome Index using a combined rational
empirical method. Test-retest reliability and measures of internal consistency
appeared adequate. Variable correlations and factor analysis were generally
consistent with our conceptualization and resulting item and variable
classifications. Practical implications for intervention integrity, program
evaluation, and organizational performance are discussed.
PMID- 11008849
TI - Mental health of refugees, internally displaced persons and other populations
affected by conflict.
PMID- 11008850
TI - Juvenile bipolar disorder.
AB - OBJECTIVE: Bipolar disorder in children and adolescents is less well studied than
bipolar disorder in adults. This review addresses issues related to its
underdiagnosis, precursors of bipolarity, comorbidity, natural course and
treatment. METHOD: Literature from Medline and other searches, and earlier
relevant articles including references from recent review articles on juvenile
bipolarity were reviewed. RESULTS: Bipolar disorder in juveniles is
underdiagnosed and misdiagnosed on various counts. Few recent studies have
reported high rates of comorbid attention deficit and disruptive disorders,
prompting some researchers to consider them as probable developmental precursors
of juvenile bipolarity. There is also evidence to suggest that some juvenile
depression could be pre-bipolar, and that certain temperamental predispositions
are probable precursors to bipolarity. Limited data on the natural course and
outcome suggest that juvenile bipolar disorder is a highly recurring illness as
in adults, and that it is associated with significant functional impairment. The
psychopharmacological treatment of juvenile bipolar disorder is remarkably
understudied, and treatment is often based on studies of adults. CONCLUSION:
There is a need for epidemiological studies of juvenile bipolar disorder.
Similarly, there is an urgent need for the methodologically rigorous studies to
establish the efficacy of various antimanic drugs. Finally, issues related to
comorbidity and temperamental predispositions to juvenile bipolarity need greater
clarity, as they may have important treatment and research implications.
PMID- 11008851
TI - The prevalence of mental health problems in Rwandan and Burundese refugee camps.
AB - OBJECTIVE: We examined the prevalence of mental health problems in refugees
living in camps that emerged in Tanzania during the Rwanda crisis that started in
1994. METHOD: Using the 28-item version of the General Health Questionnaire (GHQ
28), we examined two samples: a random sample (n = 854) and a sample of clients
of a psychosocial support programme in these camps (n = 23). Sensitivity,
specificity and positive- and negative predictive values were estimated for
several cut-off scores of the GHQ-28. RESULTS: The prevalence of serious mental
health problems was estimated at 50% (SE 12%). When using the GHQ-28 as a
screener, a cut-off score of 14 is recommended. CONCLUSION: Given the high
prevalence of mental health problems, psychosocial programmes for large refugee
populations should aim at strengthening community structures and supporting
groups instead of focusing at individuals. The screening capacity of the GHQ-28
could be used to identify mentally vulnerable groups.
PMID- 11008852
TI - The 12-month prevalence and risk factors for major depressive episode in Finland:
representative sample of 5993 adults.
AB - OBJECTIVE: This study reports the 12-month prevalence of major depressive episode
and its risk factors in a representative nationwide sample. METHOD: A random
sample of non-institutionalized Finnish individuals aged 15-75 years (N = 5993)
was interviewed in 1996. Major depressive episode during the last 12 months was
assessed using the Short Form of the University of Michigan version of the
Composite International Diagnostic Interview (the UM-CIDI Short Form). RESULTS:
The population prevalence of major depressive episode was 9.3% [95% CI 8.5,10.0],
and the age-adjusted prevalences for females and males were 10.9% [95% CI
9.7,12.0] and 7.2 [95% CI 6.2,8.2], respectively. In logistic regression analyses
the factors associated with major depressive episode after adjustment for age
were urban residency, smoking, alcohol intoxication and chronic medical
conditions. In addition, being single and obese were found to be risk factors for
males. CONCLUSION: The female to male risk ratio for major depressive episode was
smaller than in many previous studies. The sex-specific risk factor associations
warrant further investigation into sex differences in depression.
PMID- 11008853
TI - Dissociative disorders in the Sultanate of Oman.
AB - OBJECTIVE: To study the clinical manifestations and psychosocial aspects of
dissociative (conversion) disorders (DD) in the Sultanate of Oman. METHOD: A
retrospective analysis was made of data derived from case records of patients
admitted as in-patients to the Sultan Qaboos University Hospital, Oman, over a
period of 8 years. RESULTS: A higher prevalence of DD was noted in Oman compared
to western countries. The female preponderance was less marked in Oman. The most
common presentations were dissociative convulsions, dissociative motor and
dissociative trance disorders. Interpersonal difficulties with family and
academic problems were the important identified precipitants. CONCLUSION: The
study highlights the characteristic clinical and psychosocial features of the
dissociative phenomena in Oman.
PMID- 11008854
TI - Social phobia treated as a problem in social functioning: a controlled comparison
of two behavioural group approaches.
AB - OBJECTIVE: Treatments for social phobia result typically in significant anxiety
and avoidance reduction; the repercussions in terms of social functioning,
however, are not clear. This controlled study compared two approaches designed to
improve the social functioning of social phobics. METHOD: Sixty-eight socially
phobic patients were randomly assigned to two treatments focused on improving
interpersonal relationships either with or without social skills training or a
waiting list; 60 completed treatment and 59 a 1-year follow-up. Treatment was
administered in small groups, 14 sessions altogether. RESULTS: No clinically
meaningful change was observed during the waiting period. A statistically
significant and equivalent improvement obtained in both treatment conditions.
CONCLUSION: Both treatments resulted in reduced anxiety, avoidance, general
psychopathology and better social functioning that maintained over follow-up.
Continuing improvement in remission rates was noted; fully 60% of the patients no
longer fulfilled criteria for social phobia at the end of 1-year follow-up.
PMID- 11008855
TI - Relation of factor-analyzed symptom dimensions of obsessive-compulsive disorder
to personality disorders.
AB - OBJECTIVE: To assess the relation between symptom dimensions of obsessive
compulsive disorder (OCD) and comorbid personality disorders (PDs). METHOD: The
scores of 75 OCD outpatients on five previously identified symptom dimensions
were entered into multiple regression models as predictors of: 1) the presence of
any type of PD; 2) the number of PDs; 3) the presence of any cluster A, B or C
PD; and 4) the presence of each individual PD. RESULTS: Twenty-eight patients
(37.3%) met criteria for one or more PDs. High scores on the 'Hoarding' dimension
were strongly related to the presence of any Axis II diagnosis, and to the number
of PDs. Cluster C PDs (especially obsessive-compulsive and avoidant) had the
highest partial correlations with 'Hoarding'. These results were independent of
OCD symptom severity. CONCLUSION: Previous conflicting findings about the
prevalence of certain PDs in OCD might be due in part to differences in the
constitution of the particular patient groups studied.
PMID- 11008856
TI - Medication adherence in psychosis: predictors and impact on outcome. A 2-year
follow-up of first-admitted subjects.
AB - OBJECTIVE: To assess the baseline characteristics predicting poor medication
adherence following a first admission for psychosis, and the impact of poor
medication adherence on outcome. METHOD: First-admitted subjects with psychosis
(n = 65) were assessed at 6-month intervals over a 2-year follow-up. Medication
adherence was assessed using multiple sources of information. RESULTS: Baseline
lower occupational status, alcohol misuse and the intensity of delusional
symptoms and suspiciousness predicted poor medication adherence during the 2-year
follow-up. Over this period, subjects with poor medication adherence presented
more frequently with an episodic course of illness and were more frequently
readmitted, especially with regard to involuntary readmission. CONCLUSION: In
naturalistic conditions one out of two subjects with psychosis interrupts his/her
treatment in the months following his/her first discharge from hospital.
Therapeutic programmes aimed at improving medication adherence should be
implemented early in the course of psychosis to reduce the deleterious
consequences of poor medication adherence on clinical outcome.
PMID- 11008857
TI - The relationship between insight and medication adherence in severely mentally
ill clients treated in the community.
AB - OBJECTIVE: To study the relationship between aspects of insight and medication
adherence and elements of psychopathology. METHOD: Clients completed insight and
adherence measures in interview; doctors and case managers independently
completed ratings of adherence and psychopathology. Other client information was
obtained from the clinical file. RESULTS: The subscale structure of the insight
scale was well reproduced. Clients endorsed items relating to need for treatment
more than items relating to relabelling of symptoms and awareness of illness.
Self-reported insight was lower in those clients for whom either the treating
doctor or the case manager or both thought the client was non-adherent. Insight
was related positively to clinician ratings of depressed mood, and negatively to
clinician ratings of personal functioning. CONCLUSION: Our data support the
subscale structure of the insight questionnaire used, and previous suggestions
that insight is positively related to depressive affect, and inversely related to
impaired psychosocial functioning.
PMID- 11008858
TI - Swedish universities Scales of Personality (SSP): construction, internal
consistency and normative data.
AB - OBJECTIVE: A thorough revision of the Karolinska Scales of Personality (KSP) was
made by reducing the number of items and improving the psychometric quality as
concerns face validity, internal consistency and response differentiation. The
revised version was labelled The Swedish universities Scales of Personality (SSP)
and now include 91 items divided into 13 scales. METHOD: The SSP were evaluated
in a normative, randomly drawn sample (n = 741). All scales were found to be
approximately normally distributed. RESULTS: The Cronbach's alpha coefficients
ranged from 0.59 to 0.84. The mean inter-item correlations (MIIC) ranged from
0.17 to 0.43. The scale intercorrelation matrix yielded a three-factor solution
with Factor 1 reflecting Neuroticism; Factor 2 Aggressiveness; and Factor 3
reflecting Extraversion. CONCLUSION: The original KSP scales were revised,
shortened, modernized and psychometrically evaluated. The psychometric properties
and the usefulness of the test battery were found to be substantially improved.
PMID- 11008859
TI - Prospective evaluation of circulatory levels of catecholamines and serotonin in
neuroleptic malignant syndrome.
AB - OBJECTIVE: Neuroleptic malignant syndrome (NMS) may be associated with a
dysregulation of the catecholaminergic and serotonergic systems. The objective of
the present study was to evaluate prospectively the circulatory levels of
serotonin (5-HT), epinephrine (E) and dopa in patients suffering from NMS.
METHOD: Platelet-poor plasma (PPP) levels of serotonin, epinephrine and dopa in
eight NMS patients were measured twice: in the acute state and in the state of
remission. RESULTS: PPP dopa concentration was significantly lower in acute NMS
state compared to the remission state (P = 0.023). In contrast, PPP E level was
significantly higher (P = 0.019) in the acute NMS state and PPP 5-HT
concentrations in the acute state tended to be higher than those at remission (P
= 0.078). 5-HT/dopa ratio was significantly higher in the acute NMS (P = 0.015).
CONCLUSION: These results may reflect reduction in dopaminergic function and
increase in adrenergic and serotonergic activity in the acute NMS state.
PMID- 11008860
TI - Neuroleptic malignant syndrome during olanzapine and levomepromazine treatment.
AB - OBJECTIVE: To date only five reports of neuroleptic malignant syndrome (NMS)
related to olanzapine exist. The first case report was published in November
1998. METHOD: We report the case of a 78-year-old woman suffering from chronic
schizophrenia who developed a NMS while being treated with olanzapine and
levomepromazine. Before this her medication had been unchanged for more than 2
years. RESULTS: When treated with olanzapine and levomepromazine, the patient had
a fulminant NMS which was complicated with pneumonia. When the neuroleptic drug
treatment was discontinued, the patient recovered. However, when this combination
was restarted later due to severe agitation and hallucinations, the symptoms of
NMS reappeared. CONCLUSION: This case report shows that the neuroleptic malignant
syndrome can occur during olanzapine treatment as well as during treatment with
conventional neuroleptics. This syndrome may develop even after a long and stable
neuroleptic treatment.
PMID- 11008861
TI - Neurological abnormalities in schizophrenia--a 5-year follow-up study: comment on
Madsen et al.
PMID- 11008862
TI - A simple splinting technique for the mallet finger.
PMID- 11008863
TI - Pediatric analgesia and sedation for the management of orthopedic conditions.
AB - Orthopedic injuries are common in the emergency department; this is especially
true in children. The orthopedist must often supervise sedation and analgesia for
the injured child. While the techniques of conscious sedation have improved, the
therapeutic index between adequate and excessive sedation is much narrower in
children than adults, especially for painful procedures. The purpose of this
review is to outline a reasonable approach to sedation and analgesia in the
pediatric patient. In addition, current monitoring guidelines are reviewed, as
well as the basic pharmacology of the most commonly used drugs.
PMID- 11008864
TI - Total ankle replacement: a surgical discussion. Part II. The clinical and
surgical experience.
PMID- 11008865
TI - The relationship between dementia score and ambulatory level after hip fracture
in the elderly.
AB - Dementia or mental status has been considered a significant prognosticating
factor for the outcome of hip fracture in the elderly; however, the relationship
between dementia level and ambulatory level has not been investigated directly.
This study was designed to investigate the relationship between ambulatory level
and dementia level after hip fracture in the elderly. A retrospective study was
performed of 162 hip fracture patients over 65 years old. We measured the
dementia score (mini mental state test) of all patients and evaluated their
ambulatory status (divided into three groups: dependent, partially dependent, and
independent). We then investigated the relationship between ambulatory level and
dementia level. Mean dementia score for each group was as follows: dependent
group, 6.6 +/- 0.9; partially dependent group, 17.9 +/- 0.8; and independent
group, 24.6 +/- 0.4 (+/- SE). There was a significant relationship between
ambulatory level and dementia level (P< .0001).
PMID- 11008866
TI - Construct stiffness of different fixation methods for supracondylar femoral
fractures above total knee prostheses.
AB - Supracondylar fracture of the femur after total knee arthroplasty has an
estimated frequency of 0.6%-2.5% among total knee recipients and presents an
extremely difficult problem when encountered. The goal of this study is to
determine the most stable method of fixation of these supracondylar fractures
among currently available devices. Synthetic composite femurs with properties
similar to human bone were used, and identical, unstable supracondylar fractures
were created in each. Osteotomized specimens were placed into four groups of
five. Each group was then tested with one of four devices: the Green-Seligson
Henry (GSH) intramedullary nail, AO 95 degrees blade plate, dynamic condylar
screw and sideplate, and condylar buttress plate. After stabilization with the
different types of fixation, the constructs were tested individually for bending
stiffness in four modes: flexion, extension, varus, and valgus bending. The
stiffest fixation was determined in each of the four bending planes. Resistance
to all tested directions was greatest for the condylar screw and sideplate
construct. Resistance to flexion (stiffness = 30.96 N/mm), extension (stiffness =
36.36 N/mm), varus (stiffness = 35.46 N/mm), and valgus forces (stiffness = 32.26
N/mm) was highest in the group fixed with the dynamic condylar screw. This may be
due to the purchase gained by the large lag screw into the distal femur, or it
may be the result of the total rigidity of the implant. Although the femoral
samples used in this study do not duplicate the typical osteopenic bone
encountered at the site of a total knee arthroplasty, they do allow direct
comparison of the fixation devices by removing the variability associated with
cadaveric bone samples.
PMID- 11008867
TI - Quantitative anatomical study of the posterior interosseous nerve.
AB - An anatomic study of the posterior interosseous nerve (PIN) in 20 cadaver upper
limbs was performed to measure different segments of the PIN and its relationship
with radius and ulna (results given as mean +/- SD). The length of the PIN from
radial head to the arcade of Frohse (AF) was 26.5 +/- 1.6 mm and 25.3 +/- 1.1 mm
in male and female cadavers, respectively. The length of the PIN from radial head
to the PIN exit point from the supinator was 66.7 +/- 4.7 mm and 64.0 +/- 2.5 mm
in male and female cadavers, respectively. The overall length of the PIN
underlying the supinator muscle was 44.0 +/- 0.5 mm and 37.0 +/- 0.5 mm in male
and female cadavers, respectively. The distance between the PIN exit point from
the supinator and the radial margin of the radius was 15.0 +/- 0.9 mm and 14.5 +/
0.9 mm in male and female cadavers, respectively. The distance between the PIN
exit point from the supinator and ulnar margin of ulna was 18.2 +/- 0.6 mm and
17.9 +/- 0.7 mm in male and female cadavers, respectively. In 70% (n = 14) of the
cadavers, the AF was tendinous and in 30% (n = 6), it was membranous. The length,
width, and thickness of AF in males and females, respectively, were 18.6 +/- 1.2
mm / 18.5 +/- 1.3 mm; 2.8 +/- 0.4 mm / 2.5 +/- 0.4 mm; and, 0.8 +/- 0.08 mm / 0.7
+/- 0.07 mm. In all specimens, the PIN exited through the distal supinator muscle
by penetrating the muscle. The PIN exit point from the supinator belly was about
11-19 mm from distal border of the latter. The mean distances between PIN exit
point from the supinator and the origin of the extensor digitorum communis,
abductor pollicis longus, and extensor pollicis longus branches were 7.5 mm, 31
mm, and 58 mm, respectively.
PMID- 11008868
TI - Achilles tendon rupture associated with ankle fracture.
AB - The case of a 40-year-old man who sustained a medial malleolar fracture with
extension of the fracture into the tibial plafond is discussed. Before surgery,
the physical examination revealed an Achilles tendon rupture. Surgical treatment
to repair the bone and tendon injury was performed. Achilles tendon rupture is
not an uncommon injury, but it is rarely associated with a fracture. When a
fracture is present, the Achilles tendon injury can be overlooked, which may
result in a delay of treatment or residual morbidity.
PMID- 11008869
TI - A solitary osteochondroma of the pediatric thoracic spine: a case report and
review of the literature.
AB - The objective of this study design is to describe the diagnosis and successful
treatment of a pediatric patient with an osteochondroma of the thoracic spine. An
osteochondroma is a bone tumor that rarely occurs in the thoracic spine,
especially in the pediatric population. A simple painless mass may be the only
presenting symptom. The laboratory findings are usually nonspecific. Radiographs
may be nondiagnostic in certain cases, and computed tomography is the imaging
modality of choice. The diagnosis, treatment, and outcome of a pediatric patient
with an osteochondroma of the thoracic spine, including a possible genetic
predisposition, are reviewed, along with a complete review of the literature.
Anteroposterior and lateral plain radiographs illustrated a well-defined solid
mass arising from the posterior elements of the tenth thoracic vertebrae. A
computed tomography (CT) scan further delineated that the mass arose from the
spinous process with no obvious impingement of the nerve roots. After excision of
the lesion, gross pathological and histologic evaluation was consistent with an
osteochondroma. The use of CT allowed accurate diagnosis of the osteochondroma.
This led to appropriate surgical intervention, resulting in definitive treatment.
PMID- 11008870
TI - Type II Monteggia lesion with fracture-separation of the distal physis of the
radius.
AB - We report a rare case of a type II Monteggia lesion with fracture-separation of
the distal physis of the radius in a 12-year-old boy and discuss the mechanism of
this injury.
PMID- 11008871
TI - Contributing factors influencing the functional outcome of floating knee
injuries.
AB - The purpose of the present study was to retrospectively review the floating knee
injuries treated at our institute and to determine various factors, such as
severity of soft-tissue or skeletal injuries, site of fractures, and treatment
methods that may significantly influence the final functional result in these
injuries. Between 1986 and 1996, 65 patients with 66 floating knee injuries were
treated in our institution. Among 66 fractures of the femur, 19 (29%) were open.
There were 43 open tibial fractures. Fifty cases were Fraser type I floating knee
fractures, 7 were type IIa, 2 were type IIb, and 7 were type IIc. In 63 cases
(95%), both bones had been surgically stabilized with interlocked nails, Ender
pins, plates, screws with/without pinning, or external fixations. Final
functional results were evaluated according to Karlstrom and Olerud's criteria.
Satisfactory results were rated as cases with excellent or good results. The mean
follow-up time was 16.6 months range, (12-50 months). We assessed various factors
influencing functional results, including Fraser type, severity of open injury
grade (Gustilo) in both fractures, combination of open/closed injuries, fracture
types (AO/ASIF type), existence of multiple trauma, neurovascular injuries,
polyskeletal trauma, and stabilizing method or operation timing of both
fractures. Satisfactory rates in Fraser type I and type II were 64% and 25%,
respectively (P= .02). The satisfactory rate in closed, grade I+II, and grade III
injuries of the femoral fractures was 53.2%, 81.8%, and 25%, respectively (grade
I+II vs. grade III: P < .03). There were no significant correlations between the
functional result and the following factors: soft-tissue injuries of the tibia;
the fracture pattern of both fractures; the combination of open/closed injuries
in each fracture; injury severity score; the existence of neurovascular injuries
and double femoral fractures; treatment methods; and operation timing. Severity
of damage to the knee joint and open injuries in the thigh were found to be
significant factors contributing to the functional outcome in floating knee
injuries.
PMID- 11008872
TI - Targeting device for pinning finger fractures.
AB - An inexpensive targeting system for pinning phalangeal fractures is described.
PMID- 11008873
TI - Cervical spine trauma.
PMID- 11008874
TI - Semicarbazide-sensitive amine oxidases: widespread occurrence and many names and
faces.
PMID- 11008875
TI - Semicarbazide-sensitive amine oxidases in heart and bovine serum.
AB - In guinea pig dorsal skin the semicarbazide-sensitive amine oxidase (SSAO) is
localised in fibroblasts. Fibroblasts in culture lose the ability to express this
enzymatic activity with doublings, thus suggesting that the SSAO expression needs
some factors which are not present in the 10% bovine serum culture medium. Fresh
bovine serum of adult animals contains two SSAO activities, one with high
affinity for benzylamine and one with lower affinity. The enzyme with lower
affinity for benzylamine was identified as spermine oxidase, the oxidation of
[14C]-benzylamine was inhibited by semicarbazide, alpha-aminoguanidine and B24, a
specific inhibitor of benzylamine oxidase and spermine oxidase, both SSAO
enzymes. The enzymatic activity of bovine serum was partially purified, the
kinetic properties and sensitivity to inhibitors studied. A mathematical
procedure for the analysis of the kinetics resulting from the activity of two
enzymes acting on the same substrate seems to give better results than the
methods previously described.
PMID- 11008876
TI - On the primary structure of membrane-bound semicarbazide-sensitive amine oxidase
(SSAO).
AB - Mammalian semicarbazide-sensitive amine oxidase (SSAO) activities are a diverse
group of copper dependent enzymes within the classification EC 1.4.3.6.
[amine:oxygen oxidoreductase (deaminating) (copper-containing)]. They include
plasma amine oxidase and the membrane-bound enzyme. Although soluble plasma SSAO
from several species have been successfully purified and cloned, relatively
little work has been carried out on the molecular properties of the tissue-bound
enzyme. At present there is not conclusive evidence that allows to conclude
whether or not plasma SSAO is released from the tissue-bound enzyme. This review
focuses upon recent progress made in determining the primary structure of the
membrane-bound SSAO.
PMID- 11008877
TI - Age-related changes of MAO-A and -B distribution in human and mouse brain.
AB - Age-related changes of MAO-A and -B were studied in human and BL/C57 mouse brain
areas (substantia nigra, putamen and cerebellum). [3H]Ro41-1049 and
[3H]lazabemide were used as selective radioligands to image and quantify MAO-A
and MAO-B respectively by enzyme autoradiography. MAO-A binding was higher in
mouse, whereas MAO-B binding was higher in human. With aging, mouse MAO-A was
significantly reduced between 4 and 8 weeks and remained unchanged until 19
months followed by a slight increase between 19 and 25 months. In contrast, no
clear variation was observed in humans between the age of 17-93 years. In most of
the structures studied a clear age-related increase in MAO-B was observed
beginning in mouse brain at 4 weeks, whereas in human tissue this increase
started at the age of 50-60 years. These results show marked differences in the
levels and variations of mouse and human MAO-A and -B associated with aging and
should be taken into account when extrapolating experimental data from mouse to
human.
PMID- 11008878
TI - N-methyl(R)salsolinol and a neutral N-methyltransferase as pathogenic factors in
Parkinson's disease.
AB - The pathogenesis of Parkinson's disease is still an enigma. As an endogenous MPTP
like neurotoxin, N-methyl(R)salsolinol was proved to induce parkinsonism in rats
and apoptosis in dopaminergic neurons. It is synthesized in the human brain by
two enzymes; an (R)salsolinol synthase and an N-methyltransferase, and
accumulates in the nigro-striatum in human brains. The activity of a neutral N
methyltransferase in the striatum was found to determine the level of MPP+-like
1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, an oxidation product of N
methyl(R)salsolinol in the substantia nigra. The activity of this N
methyltransferase was found to increase significantly in lymphocytes prepared
from parkinsonian patients. In cerebrospinal fluid from untreated parkinsonian
patients, N-methyl(R)-salsolinol increases significantly. These results suggest
that N-methyl(R)salsolinol and a neutral N-methyltransferase may be endogenous
factors in the pathogenesis of Parkinson's disease.
PMID- 11008879
TI - Anti-apoptotic function of L-(-)deprenyl (Selegiline) and related compounds.
AB - (-)Deprenyl has been proposed to be neuroprotective to dopamine neurons in the
parkinsonian brains. To clarify the mechanism, the effects of (-)deprenyl and
structurally related compounds on apoptosis induced by a neurotoxin, N-methyl(R)
salsolinol, and reactive oxygen species, nitric oxide and peroxynitrite, were
examined in dopaminergic SH-SY5Y cells. DNA damage was quantified by the single
cell gel electrophoresis (comet) assay. (-)-Deprenyl protected the cells from
apoptosis in a dose-dependent way, which required pre-treatment at least for 20
min. The effect was confirmed even after washing out of (-)deprenyl, indicating
that (-)-deprenyl initiates the intracellular process to antagonize the apoptotic
death program. The studies on the structure-activity relationship reveal that N
propargyl residue with hydrophobic structure is essential for the anti-apoptotic
function. These results suggest that (-)deprenyl and related compounds may be
applicable as neuroprotective agents in neurodegenerative diseases.
PMID- 11008880
TI - Molecular interaction between reversible MAO-A inhibitors and the enzyme.
Application to aryloxazolidinone, a prototype series.
AB - Among the various chemical classes of monoamine oxidase A inhibitors,
phenyloxazolidinone represent one of the major series. The purpose of this paper
is to review the experimental (X-ray diffraction, NMR, electronic absorption
spectroscopy, lipophilicity studies) and theoretical (quantum chemistry,
molecular mechanics, molecular dynamics) studies which have led to the
description of the mode of interaction between phenyloxazolidinone inhibitors and
the MAO-A enzyme.
PMID- 11008881
TI - Possible different fates for the hydrogen peroxide produced by rat white
adipocyte amine oxidases.
AB - Monoamine oxidase (MAO) and benzylamine oxidases (Bz-SSAO) of rat white
adipocytes, deaminating benzylamine and tyramine produce hydrogen peroxide at
different cellular levels. The peroxide produced by their activity has a very
short half-life in adipocyte suspension. The addition of a catalase inhibitor
allows for the recovery of the intact peroxide within the first 10-min of its
production. Thus, benzylamine and tyramine-dependent peroxide recovery is
different, suggesting that the fate of the peroxide produced by the two amine
oxidases might be different depending on the cellular site of its production.
PMID- 11008882
TI - Unusual pattern of beta-phenylethylamine deamination in the rat heart.
AB - The present study was aimed to determine type A and B MAO activities in rat heart
and renal cortex homogenates and evaluate the sensitivity of deamination of 3H-5
HT and 14C-beta-PEA to selective MAO-A and MAO-B inhibitors, respectively Ro 41
1049 and lazabemide. Deamination of beta-PEA in the rat heart was not affected
(Vmax = 53+/-10 vs 42+/-6 nmol mg protein(-1) h(-1)) by lazabemide (250 nM), but
was significantly reduced (Vmax = 10+/-1 nmol mg protein(-1) h(-1)) by Ro 41-1049
(250 nM). Deamination of beta-PEA in the rat heart is a low affinity process
(when compared with that in the kidney) with high Km values (244+/-98 vs 18.6+/
5.8 microM). On the other hand, deamination of 5-HT in the rat heart and renal
cortex revealed high Km values, which were similar to those for beta-PEA in the
heart. Deamination of beta-PEA (1000 microM) in the rat heart was inhibited in a
concentration-dependent manner by Ro 41-1049 with a Ki value of 32 nM (22, 48;
95% confidence limits), but not by the selective MAO-B inhibitor lazabemide (up
to 500 nM). Inhibition of 5-HT (1000 microM) deamination in the rat heart by Ro
41-1049 was also a concentration-dependent process with a Ki value of 21 (16, 26)
nM. Deamination of 5-HT (1000 microM) in the rat renal cortex, was inhibited in a
concentration-dependent manner by Ro 41-1049 with a Ki value of 12 (8, 17) nM.
Deamination of beta-PEA in the renal cortex was inhibited by lazabemide with a Ki
of 5 (3, 7) nM. In the rat heart, in contrast to that in the renal cortex, the
specific MAO-B substrate beta-PEA is deaminated by a form of MAO which most
probably corresponds to MAO-A.
PMID- 11008883
TI - Structural approach of human MAO-A using fold recognition (threading) techniques.
AB - The major goal of the present work is to further approach the structure of human
monoamine oxidase A (MAO-A). A first partial three-dimensional model of human MAO
A has already been established using secondary structure predictions and fold
recognition methods [Wouters and Baudoux, 1998]. In this modeled structure, a
segment of the sequence (residues 369-393) located near the covalent linkage to
the essential flavin cofactor, and potentially involved in the structure of the
active site of the protein, could not be modeled. We here propose a possible fold
for that segment, based on threading techniques. The identification of regions of
the protein potentially involved in its dimerization was also undertaken by
studying hydrophobic areas present at the surface of the structure.
PMID- 11008884
TI - Steroid binding by antibodies and artificial receptors: exploration of
theoretical methods to determine the origins of binding affinities and
specificities.
AB - Binding mode calculations for complexes between an artificial paracyclophane
receptor and digoxins, cholic acids as well as cortisone steroids show
encapsulation of different ring combinations. Docking experiments were performed
between the 26-10 antibody and digoxins. Coordination affinity arises from
hydrophobic desolvation and van der Waals interactions rather than from hydrogen
bonds. The specificity and affinity arises mainly from shape complementarity.
Computed binding free energies and Kohonen neural network computations both point
to physicochemical and structural similarities of natural antibodies and
artificial receptors.
PMID- 11008885
TI - Localization and quantification of hydrophobicity: the molecular free energy
density (MolFESD) concept and its application to sweetness recognition.
AB - A method for the localization, the quantification, and the analysis of
hydrophobicity of a molecule or a molecular fragment is presented. It is shown
that the free energy of solvation for a molecule or the transfer free energy from
one solvent to another can be represented by a surface integral of a scalar
quantity, the molecular free energy surface density (MolFESD), over the solvent
accessible surface of that molecule. This MolFESD concept is based on a model
approach where the solvent molecules are considered to be small in comparison to
the solute molecule, and the solvent can be represented by a continuous medium
with a given dielectric constant. The transfer energy surface density for a 1
octanol/water system is empirically determined employing a set of atomic
increment contributions and distance dependent membership functions measuring the
contribution of the increments to the surface value of the MolFESD. The MolFESD
concept can be well used for the quantification of the purely hydrophobic
contribution to the binding constants of molecule-receptor complexes. This is
demonstrated with the sweeteners sucrose and sucralose and various halogen
derivatives. Therein the relative sweetness, which is assumed to be proportional
to the binding constant, nicely correlates to the surface integral over the
positive, hydrophobic part of the MolFESD, indicating that the sweetness receptor
can be characterized by a highly flexible hydrophobic pocket instead of a
localized binding site.
PMID- 11008887
TI - Hydration of beta-cyclodextrin: a molecular dynamics simulation study.
AB - We study by molecular dynamics simulations the hydration of beta-cyclodextrin.
Our simulations show that within these barrel-shaped molecules hydrophobicity
dominates, while at the top and bottom sides of the barrel interactions with
water are mostly hydrophilic in nature. These results agree with crystallographic
data at 120 K and, in particular, with the spontaneous hydration process of a
cyclodextrin crystal in wet atmosphere. The predicted structure of the hydration
shells is discussed and compared with previous molecular mechanics calculations
which report an overall hydrophobic behavior. Moreover, the temperature
dependence of the hydration process is discussed.
PMID- 11008888
TI - Classical QSAR and comparative molecular field analyses of the host-guest
interaction of organic molecules with cyclodextrins.
AB - The application of classical QSAR and molecular modeling analysis using
Comparative Molecular Field Analysis (CoMFA) to the complexation of some natural
and modified cyclodextrins (CDs) with guest molecules was examined. For 1:1
complexation systems between natural beta-CD, modified alpha-, beta-, and gamma
CD that bear one p-(dimethylamino)benzoyl (DMAB) moiety (DMAB-alpha-, beta-, and
gamma-CDs) and guest molecules of widely varying chemical structures and
properties, the binding constants of the complexes were successfully fitted using
multiple linear regression (MLR) with hydrophobic descriptor log P (the partition
coefficient between 1-octanol and water phases) and molecular connectivity
indices. A non-linear dependency of binding constants on the zero-th and/or first
order molecular connectivity index as a measure of size becomes apparent. The
modeling performance of the CoMFA models with steric/electrostatic fields to DMAB
alpha- and beta-CD systems was comparable to those of MLR models. However,
statistically significant CoMFA models for gamma-CD systems which have higher
conformational flexibility of the ring could not be obtained. The CoMFA models
obtained for DMAB-alpha- and beta-CD systems showed that the predominant effects
were steric for the DMAB-alpha-CD system and electrostatic for the DMAB-beta-CD
system, respectively.
PMID- 11008886
TI - 3D-QSAR using 'multiconformer' alignment: the use of HASL in the analysis of 5
HT1A thienopyrimidinone ligands.
AB - The observed 5-HT1A and alpha1-adrenergic receptor (alpha1-AR) receptor binding
properties of a series of 23 thienopyrimidinones were used to develop HASL 3D
QSAR models. A single, low energy conformer of the most active analogue in the
series, which was consistent with NMR structural studies, was chosen as a
template molecule. Alignments of all the molecules to the template were provided
by an Amber/MM2 superposition force field. In this manner, each molecule was
represented by five separate low energy conformers which were subsequently used
in the generation of HASL 3D-QSAR models. Models derived from multiple conformers
were found to exhibit enhanced predictivity compared to models based on single,
low energy conformers. In addition, the use of contour imaging of HASL multi
conformer model interactions was found to lead to a more consistent
interpretation of those molecular features most significant for 5-HT1A receptor
binding.
PMID- 11008889
TI - Indices of differences of path lengths: novel topological descriptors derived
from electronic interferences in graphs.
AB - Novel topological descriptors, namely indices of differences of path lengths
(DPs), are deduced from the physical model of wave interferences. Two electrons,
moving through a circuit graph within a diffraction experiment, interfere in a
given vertex of the graph. It is demonstrated that the overall sum of the inverse
of the squares of the differences of topological distances between all pairs of
vertices of the graph is a measure of the mean global kinetic energy of the
electrons which are able to produce a constructive interference. New topological
indices, namely indices of differences of path lengths are thus introduced as
derived from such a diffraction pattern. These indices, according to the above
expressed, should be a measure of the electron mobility within the molecule. As a
consequence, a good prediction is to be expected for properties related to such
mobility, such as resonance energy in aromatic hydrocarbons. Our results confirm
that in fact, the resonance energies are well predicted by this means. Moreover,
the new indices demonstrate to be very useful in the evaluation of biological
properties such as antibacterial activities of a wide set of heterogeneous
compounds.
PMID- 11008891
TI - Primary non familial amyloidosis of the vitreous and subretinal amyloid bodies.
AB - We report a case of primary non familial amyloidosis of the vitreous and
subretinal amyloid bodies. Pars plana vitrectomy and subretinal numerable
clusters of cystic-like glistering material were extracted. The diagnosis was
confirmed only by histological findings.
PMID- 11008890
TI - Conformational properties of amphotericin B amide derivatives--impact on
selective toxicity.
AB - Even though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene
macrolide antibiotic, is used in the treatment of severe systemic fungal
infections as a life-saving drug. To examine the influence of conformational
factors on selective toxicity of these compounds, we have investigated the
conformational properties of five AmB amide derivatives. It was found that the
extended conformation with torsional angles (phi,psi)=(290 degrees,180 degrees)
is a common minimum of the potential energy surfaces (PES) of unsubstituted AmB
and its amide derivatives. The extended conformation of the studied compounds
allows for the formation of an intermolecular hydrogen bond network between
adjacent antibiotic molecules in the open channel configuration. Therefore, the
extended conformation is expected to be the dominant conformer in an open AmB (or
its amide derivatives) membrane channel. The derivative compounds for
calculations were chosen according to their selective toxicity compared to AmB
and they had a wide range of selective toxicity. Except for two AmB derivatives,
the PES maps of the derivatives reveal that the molecules can coexist in more
than one conformer. Taking into account the cumulative conclusions drawn from the
earlier MD simulation studies of AmB membrane channel, the results of the
potential energy surface maps, and the physical considerations of the molecular
structures, we hypothesize a new model of structure-selective toxicity of AmB
derivatives. In this proposed model the presence of the extended conformation as
the only well defined global conformer for AmB derivatives is taken as the
indicator of their higher selective toxicity. This model successfully explains
our results. To further test our model, we also investigated an AmB derivative
whose selective toxicity has not been experimentally measured before. Our
prediction for the selective toxicity of this compound can be tested in
experiments to validate or invalidate the proposed model.
PMID- 11008892
TI - Changes in optic nerve head blood flow and retrobular hemodynamics following
calcium-channel blocker treatment of normal-tension glaucoma.
AB - BACKGROUND: Because calcium channel blockers reduce vascular resistance, they may
have a clinical application in the treatment of normal-tension glaucoma (NTG).
This study investigates changes in both the optic disc blood flow and the
hemodynamics of retrobulbar vessels in NTG patients after the systemic
administration of a calcium channel blocker. METHODS: Twelve eyes of 12 NTG
patients (mean age 57.6 +/- 15.3 years) were examined before and after a 4-week
treatment with 2 mg b.i.d. oral nilvadipine, an L-typc calcium channel blocker.
By scanning laser-Doppler flowmetry (SLDF), we obtained the velocity, flow, and
volume from within a 10 x 10 pixel window placed on the temporal rim region of
the optic disc perfusion map. By ultrasound color Doppler imaging (CDI), we
measured the peak systolic velocity (PSV) and the end diastolic velocity (EDV) of
the ophthalmic artery (OA), central retinal artery (CRA), nasal posterior ciliary
artery (NPCA), and temporal posterior ciliary artery (TPCA). We then calculated a
resistance index (RI) for each vessel. RESULTS: After treatment, the flow and
velocity of the optic disc blood flow significantly increased (P < 0.05).
Nilvadipine also significantly reduced RIs of the CRA, NPCA, and TPCA (P < 0.05),
and increased both the PSV of the NPCA and the EDVs of the CRA, NPCA, and TPCA.
The percent change in velocity correlated significantly with the percent changes
of the CRA RI and NPCA RI. CONCLUSIONS: Oral nilvadipine appears to reduce
orbital vascular resistance, which consequently increases the optic disc blood
flow.
PMID- 11008893
TI - Orbital color Doppler imaging of optic nerve tumors.
AB - OBJECTIVE: To report changes in retinal arterial and venous blood flow pattern in
two patients with tumors involving the entire optic nerve. METHODS: Retrospective
review of one patient with clinical and neuroimaging characteristics typical of
bilateral optic nerve gliomas and one patient with a probable meningioma of the
left optic nerve sheath. RESULTS: The optic nerve glioma patient had reduced peak
systolic velocity of central retinal arteries bilaterally, while the patient with
an optic nerve sheath meningioma had relatively low central retinal artery flow
velocity and intermittent blood flow in the central retinal vein on the affected
side. CONCLUSIONS: Reduced retinal arterial flow velocities in the setting of
optic nerve gliomas may correlate with the presence of optic nerve disease.
Phasic blood flow in the central retinal vein with optic nerve sheath meningioma
may be the reason that some patients with this tumor develop retinal choroidal
venous anastomoses.
PMID- 11008894
TI - Perfluorohexyloctane as a long-term vitreous tamponade in the experimental
animal. Experimental perfluorohexyloctane substitution.
AB - BACKGROUND: Perfluorocarbon liquids are established tools for intraoperative
hydrokinetic retinal manipulation. Because of their high specific gravity,
however, they may well cause mechanical damage to the retina when applied as a
long-term vitreous substitute. Perfluorohexyloctane, a semi-fluorinated liquid
fluorocarbon of low specific gravity (1.35 g/cm3), was developed as a long-term
vitreous substitute. The current study was performed to investigate intraocular
tolerance to perfluorohexyloctane as a long-term vitreous substitute in the
experimental animal. METHODS: 34 vitrectomised eyes of pigmented rabbits
underwent intravitreal injection of 1.0-1.2 ml perfluorohexyloctane or balanced
salt solution. In 5 eyes the anterior chamber was filled. During the follow-up
period of 3 months, the eyes were examined by slit lamp biomicroscopy, by
fluorescein angiography and by electroretinography. The eyes were then enucleated
and processed for light- and electron microscopy. RESULTS: Perfluorohexyloctane
depicted dispersion beginning between the first and third week. Over a period of
9 weeks no toxic effect on retina, lens and cornea was noticed. At 14 weeks ERG
showed a slight decrease in amplitude and early morphological changes in the
retina. CONCLUSION: Our findings suggest that perfluorohexyloctane is tolerated
in the rabbit eye for 9 weeks. Since avascular rabbit retina is more susceptible
to mechanical and toxic damage than vascularized primate retina, we suggest
proceeding from here, and investigating tolerance and quality of tamponade of
perfluorohexyl octane in man for up to 9 weeks.
PMID- 11008895
TI - Fludrocortisone in the treatment of systemic hypotension in primary open-angle
glaucoma patients.
AB - BACKGROUND: Fludrocortisone is a potent mineralocorticoid, which has no known
direct vasoactive properties, and is the first-line drug for treatment of
orthostatic hypotension. The present study evaluated the systemic hemodynamic
effects of fludrocortisone treatment in glaucoma patients. PATIENTS AND METHODS:
A retrospective analysis of the charts of glaucoma patients of the University Eye
Clinic Basel was performed. Twenty-two patients with open-angle glaucoma under
treatment with fludrocortisone were selected. The selected patients had one 24-h
blood pressure recording immediately prior to treatment with fludrocortisone and
one recording at least 2 months after starting the treatment. Parallel to blood
pressure recordings, diurnal intraocular tension curve recordings and visual
field testings were carried out. In addition, twelve patients also had nail-fold
video-capillaroscopy. RESULTS: IOP and visual fields remained stable. The average
values for all systemic blood-pressure readings showed an improvement in the
follow-up compared to primary examination. Mean (+/- SD) night-to-day ratio
('nocturnal dips') of systolic, diastolic and mean arterial blood pressure
decreased from 13.6 +/- 4.3%, 16.9 +/- 5.2% and 15.9 +/- 3.5%, respectively, to
9.9 +/- 5.9% (p = 0.01), 13.2 +/- 4.3% (p = 0.044) and 11.7 +/- 3.9% (p =
0.0004). Baseline capillary blood-flow velocity increased and capillary blood
flow standstill time after cold provocation decreased significantly under
fludrocortisone therapy. CONCLUSION: Hemodynamic parameters show a tendency
towards improvement in a magnitude which might be of clinical relevance.
PMID- 11008896
TI - Contrast sensitivity in patients recovered from central serous chorioretinopathy.
AB - OBJECTIVE: To study contrast sensitivity in patients who have recovered from
central serous chorioretinopathy (CSC). PATIENTS AND METHODS: Thirty-one patients
who had recovered from CSC were examined with the Vistech and Pelli-Robson
contrast sensitivity charts. The time from the onset of the active disease varied
from 10 to 166 months (mean 60.4 +/- 42.0, SD). The visual acuity was 1.0 (logMar
0) or better. RESULTS: Contrast sensitivity of the affected eyes was
significantly worse in the intermediate spatial frequencies of 3 and 6 cycles per
degree (cpd) in the Vistech test compared to the fellow eyes (p = 0.032, 0.013,
respectively). Contrast sensitivity of the affected eyes was significantly worse
in all 5 spatial frequencies of the Vistech test and in the Pelli-Robson test
compared to age-matched normal eyes (p = 0.006, 0.000, 0.000, 0.018, 0.000,
0.000, respectively). Contrast sensitivity of the fellow eyes was significantly
worse in the spatial frequencies of 3 and 18 cpd in the Vistech test and in the
Pelli-Robson test compared to age-matched normal eyes (p = 0.020, 0.019, 0.000,
respectively). CONCLUSIONS: Contrast sensitivity does not seem to recover in all
eyes after CSC even if the visual acuity has returned to normal. Therefore,
contrast sensitivity testing is recommended for the patients complaining of
visual impairment in spite of good visual acuity.
PMID- 11008897
TI - Electrocardiographic changes during subconjunctival injections.
AB - Electrocardiographic changes were investigated in 53 patients during
subconjunctival drug injections. Decrease in heart-rate of more than 10% or
arrhythmia was observed in 25 (47.2%) of the patients, who were considered to
have a positive oculocardiac reflex. In the control group of 35 patients, only 3
(8.6%) were found to have a significant decrease in heart rate during blood
sampling from antecubital vein (p = 0.000). Young age was a significant risk
factor for oculocardiac reflex during injections (p = 0.01). Patient gender,
verbal pain score, satiety, experience of periocular injections, injected drug
type were not found to be risk factors. All patients with oculocardiac reflex
were asymptomatic; however, it is still wise to have emergency supplies ready for
any circulatory derangement during subconjunctival injections.
PMID- 11008898
TI - Ophthalmologic outcome of transvenous embolization of spontaneous carotid
cavernous fistulas: a preliminary report.
AB - We give a preliminary report of the ophthalmologic outcome of four patients with
transvenous embolization studied for their spontaneous carotid-cavernous
fistulas. One of them is a direct type while three of them are indirect dural
shunts. In indirect dural shunts, traditional transarterial embolization rarely
achieves a complete clinical cure in a short period of time. All cases had an
ophthalmologic disturbance justified for endovascular intervention. We performed
catheterization, and subsequently embolization with Guglielmi Detachable coils,
to the cavernous sinus via the femoral vein and inferior petrosal sinus/superior
ophthalmic vein. All four patients achieved clinical and angiographic improvement
with a follow-up period range from two to sixteen months except for one patient
who had residual bilateral sixth nerve palsy. The transvenous approach offers an
effective and safe alternative for the management of spontaneous carotid
cavernous fistula.
PMID- 11008899
TI - Visual outcomes after cataract surgery and cataract surgical coverage in India.
AB - Visual outcomes of 2369 cataract operated persons(3655 eyes) across seven major
Indian states were assessed in 1998. This is the largest ever study over the past
decade in the country. 9.54 per cent of the examined population had undergone
operation for cataract in one or both eyes. Intra-capsular cataract extraction
was the commonest surgical modality adopted (91.62%). Intraocular lens implants
resulted in better visual outcomes with 71.4 per cent of such patients achieving
a good visual outcome (> or = 6/18 in operated eyes). Visual outcome was also
good if ICCE operated patients were provided good quality aphakic spectacles.
There were no gender differentials in surgical uptake rates. The risk of poor
postsurgical visual outcome was strongly associated by type of surgery (Adjusted
OR for ICCE-2.78; 95% CI: 1.41-5.49) and the non-availability or poor quality
aphakic spectacles (Adjusted OR for poor/no spectacles 4.59-95% CI: 3.53-5.97).
Duration since surgery and the source of surgery did not influence visual
outcomes. Half the cataract blind remained unoperated in the study population.
PMID- 11008901
TI - Epidemiological research at the American Cancer Society.
PMID- 11008900
TI - Visual outcome and complications after posterior capsule rupture during
phacoemulsification surgery.
AB - PURPOSE: To determine the visual outcome and incidence of complications after
posterior capsule rupture during phacoemulsification surgery. METHODS: Forty-four
eyes of 43 patients which sustained posterior capsule rupture or zonulysis during
phacoemulsification surgery between April 1993 and May 1996 were retrospectively
studied. Eyes With pseudoexfoliation syndrome, traumatic cataract and myopia > 6
dioptres were excluded from the study. The mean postoperative follow-up period
was 26 months (range 3 to 47 months). RESULTS: Forty-one eyes had posterior
capsule rupture and 3 eyes had zonulysis. Of these 44 eyes, 41 eyes had vitreous
loss and anterior vitrectomy at the time of surgery or subsequently. Excluding 2
eyes with pre-existing conditions that precluded good vision, 36 out of 42 eyes
(85.7%) achieved spectacle corrected visual acuity of 6/12 or better post
operatively. Of all 42 eyes, 20 had anterior chamber intraocular lens (ACIOL)
implantation while the others had posterior chamber intraocular lens (PCIOL)
implantation. For eyes with ACIOL, 17 out of 20 eyes (85.0%) had best corrected
visual acuity of 6/12 or better. For eyes with PCIOL, 19 out of 22 eyes (86.4%)
had best corrected visual acuity of 6/12 or better. CONCLUSIONS:
Phacoemulsification surgery, even if complicated by posterior capsule rupture or
zonulysis, is compatible with good visual outcome. This is provided prompt
attention is paid to the management of complications.
PMID- 11008902
TI - Cancer and Mediterranean dietary traditions.
AB - The incidence of cancer overall in Mediterranean countries is lower than in
Scandinavian countries, the United Kingdom, and the United States. This is mostly
accounted for by the lower incidence among Mediterranean countries of cancer of
the large bowel, breast, endometrium, and prostate. These forms of cancer have
been linked to dietary factors, particularly low consumption of vegetables and
fruit, and to a certain extent, high consumption of meat. The traditional
Mediterranean diet is characterized by high consumption of foods of plant origin,
relatively low consumption of red meat, and high consumption of olive oil, which
in several studies has been reported to be more beneficial against cancer than
other forms of added lipids. By taking into account the established or presumed
nutritional causation of major forms of cancer and the composition of the
traditional Mediterranean diet, estimates can be derived concerning the fraction
of cancer occurrence in highly developed Western countries that could be
attributed to their diets in comparison with the healthy traditional
Mediterranean diet. Although estimates can only be crude, it can be calculated
that up to 25% of the incidence of colorectal cancer, approximately 15% of the
incidence of breast cancer, and approximately 10% of the incidence of prostate,
pancreas, and endometrial cancer could be prevented if the populations of highly
developed Western countries could shift to the traditional healthy Mediterranean
diet.
PMID- 11008903
TI - Prostate cancer risk in relation to anthropometry and physical activity: the
National Health and Nutrition Examination Survey I Epidemiological Follow-Up
Study.
AB - We studied the relationship of prostate cancer to anthropometry and self-reported
physical activity among 5377 African-American and Caucasian participants in the
National Health and Nutrition Examination Survey I cohort. The cohort was first
examined between 1971 and 1975 and then followed prospectively through the
Epidemiologic Follow-up Study in 1982-1984, 1986, 1987, and 1992. Men who
reported low levels of nonrecreational physical activity had increased risk of
prostate cancer compared with very active men. These findings were unchanged
after adjustment for potential confounders and were stronger for African
Americans (relative risk, 3.7; 95% confidence interval, 1.7-8.4) than for
Caucasians (relative risk, 1.7; confidence interval, 0.8-2.3). Lower levels of
recreational activity were weakly associated with increased prostate cancer risk
among African-Americans but not among Caucasians. Prostate cancer risk was
unrelated to a variety of anthropometric variables. These results suggest that
inactive men are at increased risk of prostate cancer.
PMID- 11008904
TI - Serum selenium and subsequent risk of prostate cancer.
AB - It is suspected that selenium is protective against prostate cancer. To test this
hypothesis, we conducted a nested case-control study in a cohort of 9345 Japanese
American men examined between 1971 and 1977. At the time of examination, a blood
specimen was obtained, and the serum was frozen. After a surveillance period of
more than 20 years, 249 tissue-confirmed incident cases of prostate cancer were
identified. Their stored sera and those of 249 matched controls were measured for
selenium levels. Odds ratios for prostate cancer, based on quartiles of serum
selenium levels, were determined using the General Estimating Equations approach.
The multivariate odds ratio for the highest quartile was 0.5 (95% confidence
interval, 0.3-0.9) with a two-sided P for trend of 0.02. The inverse association
was more notable for cases with advanced disease and for cases diagnosed 5-15
years after phlebotomy. However, the association was mainly present in current or
past cigarette smokers rather than nonsmokers, which leads to caution in the
interpretation of the results.
PMID- 11008905
TI - Gene-covariate interaction between dysplastic nevi and the CDKN2A gene in
American melanoma-prone families.
AB - The CDKN2A gene has been implicated in cutaneous malignant melanoma pathogenesis.
Although CDKN2A mutations confer substantial risk for melanoma,
clinicoepidemiological covariates including dysplastic nevi (DN), total nevi, and
solar injury also enhance melanoma risk. To examine the relationship between
CDKN2A and these three risk factors, we conducted combined segregation/linkage
analysis using the class D regressive logistic model, as implemented in the
computer program REGRESS. Genetic and covariate data were collected on 20
American melanoma-prone families, 13 of which had cosegregating CDKN2A mutations.
Two types of analyses were conducted. The missing-indicator method used a missing
value indicator, set to 1 for unknown and 0 for known covariate status, and a
second variable set to 1 for exposed and 0 for unexposed or unknown. The second
method, complete-cases method, coded subjects with missing covariates as unknown
for the affection status. The results for both analyses were very similar.
Overall, there was a significant improvement in the likelihood when DN, total
nevi or both covariates were added to the base model, which included dominant
transmission of the CDKN2A gene and a linear increase of risk with the logarithm
of age on the logit scale. In contrast, inclusion of solar injury did not
significantly improve the likelihood for the base model. Significant evidence for
a gene-covariate interaction was detected between DN and CDKN2A when DN was the
only covariate in the model (missing-indicator method or complete-cases method)
or when both DN and total nevi were in the model (complete-cases method only).
Interestingly, in both methods, the odds ratio (OR) for DN was greater in
subjects without mutations (OR, 20.1; 95% confidence interval, 4.8-92.8) versus
those with CDKN2A mutations (OR, 3.3; 95% confidence interval, 1.1-10.0; complete
cases method). The CDKN2A-DN interaction illustrates the complex etiology of
melanoma and needs to be confirmed in a larger sample of families.
PMID- 11008906
TI - Empirical Bayes adjustments for multiple results in hypothesis-generating or
surveillance studies.
AB - Traditional methods of adjustment for multiple comparisons (e.g., Bonferroni
adjustments) have fallen into disuse in epidemiological studies. However,
alternative kinds of adjustment for data with multiple comparisons may sometimes
be advisable. When a large number of comparisons are made, and when there is a
high cost to investigating false positive leads, empirical or semi-Bayes
adjustments may help in the selection of the most promising leads. Here we offer
an example of such adjustments in a large surveillance data set of occupation and
cancer in Nordic countries, in which we used empirical Bayes (EB) adjustments to
evaluate standardized incidence ratios (SIRs) for cancer and occupation among
craftsmen and laborers. For men, there were 642 SIRs, of which 138 (21%) had a P
< 0.05 (13% positive with SIR > 1.0 and 8% negative with SIR < or = 1.0) when
testing the null hypothesis of no cancer/occupation association; some of these
were probably due to confounding by nonoccupational risk factors (e.g., smoking).
After EB adjustments, there were 95 (15%) SIRs with P < 0.05 (10% positive and 5%
negative). For women, there were 373 SIRs, of which 37 (10%) had P < 0.05 before
adjustment (6% positive and 4% negative) and 13 (3%) had P < 0.05 after
adjustment (2% positive and 1% negative). Several known associations were
confirmed after EB adjustment (e.g., pleural cancer among plumbers, original SIR
3.2 (95% confidence interval, 2.5-4.1), adjusted SIR 2.0 (95% confidence
interval, 1.6-2.4). EB can produce more accurate estimates of relative risk by
shrinking imprecise outliers toward the mean, which may reduce the number of
false positives otherwise flagged for further investigation. For example, liver
cancer among chimney sweepers was reduced from an original SIR of 2.2 (range, 1.1
4.4) to an adjusted SIR of 1.1 (range, 0.9-1.4). A potentially important future
application for EB is studies of gene-environment-disease interactions, in which
hundreds of polymorphisms may be evaluated with dozens of environmental risk
factors in large cohort studies, producing thousands of associations.
PMID- 11008907
TI - N-Acetyltransferase-2 genetic polymorphism, well-done meat intake, and breast
cancer risk among postmenopausal women.
AB - Heterocyclic amines found in well-done meat require host-mediated metabolic
activation before initiating DNA mutations and tumors in target organs.
Polymorphic N-acetyltransferase-2 (NAT2) catalyzes the activation of heterocyclic
amines via O-acetylation, suggesting that NAT2 genotypes with high O
acetyltransferase activity (rapid/intermediate acetylator phenotype) increase the
risk of breast cancer in women who consume well-done meat. To test this
hypothesis, DNA samples and information on diet and other breast cancer risk
factors were obtained from a nested case-control study of postmenopausal women.
Twenty-seven NAT2 genotypes were determined and assigned to rapid, intermediate,
or slow acetylator groups based on published characterizations of recombinant
NAT2 allozymes. NAT2 genotype alone was not associated with breast cancer risk. A
significant dose-response relationship was observed between breast cancer risk
and consumption of well-done meat among women with the rapid/intermediate NAT2
genotype (trend test, P = 0.003) that was not evident among women with the slow
acetylator genotype (trend test, P = 0.22). These results suggest an interaction
between NAT2 genotype and meat doneness, although a test for multiplicative
interaction was not statistically significant (P = 0.06). Among women with the
rapid/intermediate NAT2 genotype, consumption of well-done meat was associated
with a nearly 8-fold (odds ratio, 7.6; 95% confidence interval, 1.1-50.4)
elevated breast cancer risk compared with those consuming rare or medium-done
meats. These results are consistent with a role for O-acetylation in the
activation of heterocyclic amine carcinogens and support the hypothesis that the
NAT2 acetylation polymorphism is a breast cancer risk factor among postmenopausal
women with high levels of heterocyclic amine exposure.
PMID- 11008908
TI - Tamoxifen and mammographic breast densities.
AB - The extent of breast tissue density on mammograms is one of the strongest risk
factors for breast cancer. The aim of this analysis was to evaluate whether
tamoxifen can affect mammographic breast density. Subjects were participants in
the National Surgical Adjuvant Breast Project Breast Cancer Prevention Trial
(BCPT), recruited and followed at the Breast Center of Saint-Sacrement Hospital
in Quebec City, Canada. The Breast Cancer Prevention Trial is a double-blind
trial in which women at high risk of breast cancer were randomized to receive
either 20 mg tamoxifen per day or placebo. Mammograms were taken before treatment
began and yearly thereafter. For the purpose of this analysis, Wolfe's
parenchymal pattern and the percentage of the breast showing tissue densities
were assessed by review of pre- and posttreatment mammograms without knowledge of
treatment assignment. Among the 69 women included in this analysis, 36 received
tamoxifen and 33 received placebo for an average of 3.3 and 3.5 years,
respectively. Among women receiving tamoxifen, 16 of 36 (44.4%) changed to a
parenchymal pattern of lower density compared with 5 of 33 (15.2%) women
receiving placebo (P = 0.010). Moreover, in the tamoxifen-treated group, the
difference in the percentage of the breast showing tissue densities between the
pre- and posttreatment mammograms reached -9.4% on average compared with a
reduction of -3.6% in the placebo group (P = 0.010). Our data show that tamoxifen
can reduce high-risk mammographic features. Breast densities should be evaluated
as possible early markers of the preventive effect of selective estrogen receptor
modulators.
PMID- 11008909
TI - Effect of tamoxifen on mammographic density.
AB - There are strong data showing that increased breast cancer risk is associated
with increased mammographic density. Tamoxifen has been shown to decrease the
risk of invasive breast cancer and decrease breast density. We sought to
demonstrate and calculate the extent of change in mammographic density in women
who have taken tamoxifen for up to 2 years. We evaluated mammograms from 28 high
risk women who were taking tamoxifen. Four different methods of evaluation were
used: (a) two qualitative methods (Wolfe criteria and the American College of
Radiology Breast Imaging and Reporting Data System criteria); (b) one
semiquantitative method (mammograms were assigned one of five semiquantitative
scores by visual inspection); and (c) one quantitative method (computer-aided
calculation of fibroglandular area from digitized mammograms). The Wolfe criteria
showed a 0.03 category decrease per year (P = 0.50). The American College of
Radiology Breast Imaging and Reporting Data System criteria showed a 0.1 category
decrease per year (P = 0.12). Semiquantitative criteria showed a 0.2 category
decrease per year (P = 0.039). Digitized scores showed a 4.3% decrease per year
(P = 0.0007). In conclusion, tamoxifen causes a decrease in mammographic density
with use, an effect that is better quantitated with semiquantitative criteria or
digitized images. Density change might become useful as a surrogate end point for
the effect of tamoxifen and other chemopreventive measures, although our data do
not predict an individual's degree of risk reduction.
PMID- 11008910
TI - Effectiveness and cost-effectiveness of multiple outcalls to promote mammography
among low-income women.
AB - A multiple outcall approach based on the Transtheoretical Model was used to
encourage mammography behavior in low-income women in the state of Colorado.
Women (n = 983) were recruited in person at grocery and discount stores and were
then called over the telephone to receive the multiple outcall intervention.
These women were compared with 3,080 women who were recruited by telephone and
randomly assigned to three study groups: health survey only (control); single
outcall; or advance card + single outcall. Subsequent mammography behavior was
assessed through a telephone interview conducted 6 months after initiation of the
protocol. After controlling for baseline differences between groups in age,
education, income, health status, and previous mammography behavior, the multiple
outcall intervention was significantly related to mammography behavior among
women nonadherent at baseline (odds ratio, 2.58; 95% confidence interval, 1.45
4.60). Furthermore, women who received the multiple outcall intervention had
higher "stage of change" at follow-up and more positive attitudes toward
mammography. Cost-effectiveness analysis indicated that although the multiple
outcall intervention was more costly to deliver ($14.84 per subject compared with
about $7.00 for the single outcall interventions), it cost considerably less per
subject converted from nonadherent to adherent. Despite study design limitations,
the multiple outcall intervention appears to be an effective method of promoting
mammography among previously nonadherent women. The results suggest that a
combined approach, in which nonadherent women receive multiple calls promoting
screening behavior, followed by single calls at the appropriate intervals to
promote repeat screening, may be a useful strategy in defined populations.
PMID- 11008911
TI - A case-control study of analgesic use and ovarian cancer.
AB - A recent case-control study raised the hypothesis that acetaminophen use 1 day or
more per week for at least 6 months reduces the risk of epithelial ovarian
cancer. We assessed analgesic use in relation to epithelial ovarian cancer risk
using data from our case-control surveillance study of medication use and cancer.
Patients were interviewed in hospitals in Baltimore, Boston, New York, and
Philadelphia during 1976-1998. We compared 780 women with epithelial ovarian
cancer to 2053 cancer controls and 2570 noncancer controls. For acetaminophen use
1 day or more per week for at least 6 months, the odds ratio estimate was 0.9
(95% confidence interval, 0.6-1.4) derived with cancer controls and 1.0 (0.6-1.5)
with noncancer controls. Estimates for more frequent and longer term use were
also compatible with 1.0. The odds ratios among patients with metastatic ovarian
cancer were reduced but not statistically significant. The odds ratio for use of
nonsteroidal anti-inflammatory drugs 4 or more days per week for at least 5
years, 0.5, was statistically significant. The present results provide only weak
support for a reduction in the risk of epithelial ovarian cancer among
acetaminophen users. They raise the possibility of an inverse association with
long-term nonsteroidal anti-inflammatory drug use.
PMID- 11008912
TI - Precision and bias of food frequency-based measures of fruit and vegetable
intakes.
AB - Accurate assessment of fruit and vegetable intakes is critical for cancer control
research and public health surveillance. This report examines the bias and
precision of two commonly used food frequency questionnaire methods to assess
fruit and vegetable intakes: (a) the 5 A Day method, based on seven items; and
(b) the summation method, based on adding total servings of all fruit and
vegetable items on a comprehensive (100+ item) food frequency questionnaire. Data
are from three studies in which 24-h dietary recalls, food records, or serum
carotenoid concentrations could be used as criterion measures (n = 260, 1031, and
342). Studies differed markedly in distributions of participants' age,
race/ethnicity, sex, and socioeconomic status. Mean intakes of total fruit and
vegetables based on the 5 A Day method were consistently lower than those from
either the summation method (3.11 versus 4.06), 24-h recalls (3.32 versus 4.07),
or food records (3.11 versus 3.46; all P < 0.01), and this was due primarily to
underestimates of vegetable intake. Correlations of the 5 A Day and summation
measures with all criterion measures were similar and were consistently higher
for fruit (range, 0.33-0.57) than for vegetables (range, 0.24-0.32). These
results, which were consistent across diverse participant samples, suggest that
the 5 A Day method yields both biased and imprecise measures of vegetable intake
and that research to improve this measure is needed.
PMID- 11008913
TI - Human papillomavirus testing for primary screening of cervical cancer precursors.
AB - Our objective was to determine whether the addition of human papillomavirus (HPV)
testing to screening cytology improves the detection of cervical cancer
precursors. Women of ages 18-69 years underwent conventional Pap cytology and HPV
DNA testing in a multicenter study in Newfoundland, Canada. Those with positive
cytology and/or HPV and a random sample of those with dual negative results were
referred for colposcopy. The study enrolled 2098 women. The relative sensitivity
of HPV testing was significantly higher than cytology for all-grade squamous
intraepithelial lesions [SILs; 73%; 95% confidence interval (CI), 62-82] and high
grade SILs (HSILs; 90%; 95% CI, 74-97) but had lower relative specificity (62%
for all-grade SILs and 51% for HSILs) than most cytological cutpoints. The rate
of combined correct results for all-grade lesions was higher for HPV testing
(68.8%) than for any cytological cutpoint (equivocal, 52.3%; LSILs, 51.6%; HSILs,
44.5%). The combination of HPV and an LSIL cutpoint had a negative predictive
value of 68% (95% CI, 52-80) for all SILs and 100% (95% CI, 91-100) for HSILs,
while referring for colposcopy only 12% of the women. We concluded that HPV
testing in conjunction with cytology improved the screening efficacy of cytology
alone and may allow for a more effective and safe primary screening program with
increased screening intervals.
PMID- 11008914
TI - Correlates of the spread of human papillomavirus infection.
AB - Knowledge of the correlates of human papillomavirus (HPV) seropositivity is of
interest for planning of preventive measures and for evaluation of possible
confounding in epidemiological studies. The epidemiological determinants for
seropositivity for oncogenic and benign HPV types were assessed using a
serosurvey of 275 healthy Swedish women, stratified by age and lifetime number of
sexual partners. Seroprevalences were compared with 17 behavioral variables
obtained by interview and 3 laboratory-diagnosed microbiological exposures. In
univariate analysis, history of gonorrhea and condylomatosis, human herpesvirus
type 8 and herpes simplex virus 2 seropositivities, lifetime number of sexual
partners, and current partner's lifetime number of sexual partners were
associated with oncogenic HPV seropositivity. Noteworthy lack of correlations
included smoking habits and oral contraceptive use. In multivariate analysis,
only the number of lifetime sexual partners [odds ratio (OR), 8.7; 95% confidence
interval (CI), 3.3-22.6] and seropositivity for benign HPV types remained
significant (OR, 2.9; 95% CI, 1.6-5.3). Seropositivity for benign HPV was
primarily associated with condyloma history (OR, 3.6; 95% CI, 1.2-10.8) and
seropositivity for oncogenic HPV (OR, 2.9; 95% CI, 1.6-5.2). An association with
sexual history lost significance in the multivariate model. In conclusion,
lifetime number of sexual partners is the major determinant of acquisition of
oncogenic HPV. By contrast, benign HPV infection associates more strongly with
condyloma history than with sexual history per se.
PMID- 11008915
TI - Helicobacter pylori and stomach cancer: a case-control study in Venezuela.
AB - The role of Helicobacter pylori infection in gastric cancer was evaluated in a
high-risk population in Venezuela using serological assays in a study of 302
cases and 483 neighborhood controls. To investigate the claim that assays for H.
pylori should use antigens derived from local strains, four different assays
derived from Venezuelan and European strains were used. Prevalence of IgG H.
pylori antibodies in controls was very high, with estimates between 72 and 92%.
Prevalence was similar in cases and controls. However, cases had lower antibody
titers. This effect was observed only in subjects with low pepsinogen (PG) levels
PGI/PGII <3.0), which suggested that extensive atrophy in cases causes a loss of
H. pylori infection, with a consequent reduction in antibody titer. In addition,
advanced cases (stage II or higher) had lower antibody titers than less advanced
cases, which indicated that the lower antibody titers in cases may be
attributable partially to a diminished immune response. All of the four assays
for anti-H. pylori antibodies gave similar results. No evidence was found for the
superiority of the assay based on Venezuelan strains. These results are
consistent with other case-control studies in high-risk populations and highlight
the difficulties of investigating H. pylori infection in retrospective studies.
PMID- 11008916
TI - Parental smoking and alcohol consumption and risk of neuroblastoma.
AB - Previous studies and animal evidence have suggested a relationship between
parental tobacco or alcohol use and the risk of some childhood cancers, including
neuroblastoma. A case-control study was conducted to investigate the relationship
between parental tobacco smoking, alcohol consumption, and risk of neuroblastoma.
Cases were children diagnosed with neuroblastoma over the period 1992-1994 at
Children's Cancer Group and Pediatric Oncology Group institutions throughout the
United States and Canada. One matched control was selected using random-digit
dialing. Information on parental smoking and drinking history was obtained from
504 case and 504 control parents by telephone interview. Overall, there was no
consistent pattern of association with parental smoking and alcohol consumption.
For example, both maternal smoking and drinking during the period from 1 month
before pregnancy through breastfeeding had adjusted odds ratios (ORs) of 1.1 [95%
confidence interval (CI), 0.8-1.4]. There was no association with paternal
smoking (OR, 1.2; 95% CI, 0.8-1.6) or paternal drinking 1 month before conception
(OR, 1.0; 95% CI, 0.7-1.4). There was no consistent increase in risk by the
amount of smoking or drinking during any time period relative to pregnancy. There
was no suggestion of an increased risk when only one parent smoked. Smoking or
drinking among both parents did not jointly increase the risk of neuroblastoma in
their offspring. The child's age at diagnosis, stage, or MYCN oncogene
amplification status did not materially alter the OR estimates. It is concluded
that the results from this study do not indicate any evidence for a relationship
between neuroblastoma and parental tobacco or alcohol use.
PMID- 11008917
TI - Relationships among breast cancer perceived absolute risk, comparative risk, and
worries.
AB - When trying to predict breast cancer screening, it may be important to understand
the relationships between perceived breast cancer risks and worries about getting
breast cancer. This study examines the extent to which women's worries about
breast cancer correlate with perceptions of both absolute (assessment of own) and
comparative (self versus other) 10-year and lifetime risks. As part of a larger
randomized intervention trial concerning hormone replacement therapy, 581 women
participated in a telephone baseline survey to assess their perceptions of breast
cancer risks and worries. Worries about getting breast cancer in the next 10
years and in one's lifetime were related positively to both absolute and
comparative 10-year and lifetime risks. The magnitude of these relationships did
not differ by time frame. Worry about breast cancer is a function of both how a
woman views her own risk and how she compares her risk with that of other women.
Some practitioners may encourage women to get screened for breast cancer by using
emotional appeals, such as heightening women's worries about breast cancer by
using risk information. Our data suggest that they should give careful
consideration how best to combine, if at all, information about absolute and
comparative risks. For example, if the motivation to screen is based on a
sequential assessment of risk beginning with comparative and then absolute risk,
creating communications that heighten perceived risk on both of these risk
dimensions may be needed to evoke sufficient worry to initiate breast cancer
screening.
PMID- 11008918
TI - Consumer perception of risk associated with filters contaminated with glass
fibers.
AB - The filters in Eclipse, a new cigarette-like smoking article marketed by R. J.
Reynolds Tobacco Company, are contaminated with glass fibers, fragments, and
particles. Reported herein are the results of a study in which consumers were
questioned about their opinions as to whether exposure to glass fibers in such a
filter poses an added health risk beyond that from smoking and whether the
manufacturer has an obligation to inform consumers about the glass contamination
problem. The study queried 137 adults who were interviewed while waiting at a
Division of Motor Vehicles office in Erie County, New York in 1997. All but one
person expressed the view that the presence of glass fibers on the filters poses
an added health risk beyond that associated with exposure to tobacco smoke alone.
Nearly all expressed the position that the cigarette manufacturer has a duty to
inform the public about the potential for glass exposure.
PMID- 11008919
TI - Helicobacter pylori strain types and risk of gastric cancer: a case-control
study.
AB - The aim of this novel endoscopy clinic-based case-control study was to explore
the influence of different Helicobacter pylori strain types on the risk of
gastric adenocarcinoma using isolated bacterial strains, tissue samples, and
sera. We included 72 cases with gastric adenocarcinoma and 324 age- and sex
matched controls. Histological characterization, culture, molecular typing of H.
pylori genes by PCR (cagA/vacA), conventional IgG ELISA, and immunoblotting
(Western blot) for the CagA and VacA proteins were performed. With four tests
combined, H. pylori infection was detected in 57 (79%) cases and 213 (66%)
controls. A positive association between H. pylori infection and gastric cancer
risk was found [odds ratio (OR), 2.1; 95% confidence interval, 1.1-3.9]. Type I
(OR, 1.8), intermediate (OR, 2.0), and type H (OR, 0.2) strains of H. pylori
presented different serum antibody levels and different levels of association
with gastric cancer. Our case-control study, based on molecular characterization
and serology, provides further evidence that infection by more virulent strains
of H. pylori and the presence of antibodies toward the CagA protein can be used
as markers for an increased risk of gastric adenocarcinoma and that the strain
types of H. pylori could be used in the future to determine disease outcome.
PMID- 11008920
TI - CYP1A1 I462V genetic polymorphism and lung cancer risk in a cohort of men in
Shanghai, China.
AB - Cytochrome P450 (CYP) CYP1A1 activates tobacco-related carcinogens. A point
mutation at codon 462 in exon 7 of CYP1A1 results in a substitution of isoleucine
by valine near the heme binding site. This mutation is rare in Caucasians but
common in Japanese populations, in which association with increased risk of lung
cancer has been reported. There are few data in other Asian populations. We
investigated this I462V polymorphism using DNA from 214 incident cases of lung
cancer and 669 controls in a prospective cohort study of 18,244 middle-aged and
older men in Shanghai, China. The valine allele frequency was 0.138 among the
control population. The I462V genotype was not appreciably associated with lung
cancer risk overall. There was some suggestion that having at least one valine
allele might be related to increased risk of lung cancer among smokers of <20
cigarettes/day (odds ratio, 1.72; 95% confidence interval, 0.82-3.62),
particularly among those with homozygous deletion of GSTM1 (odds ratio, 2.80; 95%
confidence interval, 1.07-7.33), which is involved in the detoxification of
activated tobacco carcinogens. In this Chinese cohort, with CYP1A1 valine allele
frequency intermediate between Japanese and Caucasian populations, the I462V
polymorphism is not related to lung cancer overall, but it might play a role at
lower levels of cigarette smoking among subjects with impaired carcinogen
detoxification as assessed by the GSTM1-null genotype.
PMID- 11008921
TI - Expression of protein mediators of type I interferon signaling in human squamous
cell carcinoma of the skin.
AB - IFN-based therapy has been shown to be active in the treatment of squamous cell
carcinoma (SCC) of the skin and has promise for chemoprevention and treatment of
several other cancers. In an effort to better understand the molecular mechanism
of this activity, we have determined the expression pattern of several of the
protein mediators of type I IFN signaling by immunohistochemistry in cutaneous
SCC, SCC metastases, and adjacent nonmalignant epithelium from patient biopsies.
All of the proteins, signal transducer and activator of transcription (STAT)
1alpha/beta, STAT2, p48, STAT3a, and STAT3beta, are expressed at varying levels
in the adjacent epidermis, as well as in other epidermal and dermal cell types.
For the majority of samples tested, the expression of one or more of these
proteins was reduced in SCC primary tumors compared with the adjacent
nonmalignant epithelial cells, as determined by manual scoring. Quantitative
densitometry of several samples revealed differences that are statistically
significant. Our study provides the first direct evidence for the expression of
the IFN-stimulated gene factor 3 (STAT1alpha/beta, STAT2, and p48) and STAT3alpha
and STAT3beta mediators of IFN-alpha/beta signaling in human skin and skin
derived SCCs. These data have led to the hypothesis that the loss of IFN
sensitivity may contribute to the development and progression of skin SCC.
PMID- 11008923
TI - Hydrochloric attack of serpentinites: Mg2+ leaching from serpentinites.
AB - This paper presents the hydrochloric attack of serpentinites. Romanian
serpentinites are part of the Danubian crystalline complex. These serpentinites
contain mineral serpentine (magnesium silicate) and a small amount of other
minerals along with calcium, iron, aluminium, nickel, cobalt, chrome and
manganese. For processing, the serpentinite was attacked by hydrochloric acid
from two provinces (p.a. and residual hydrochloric acid), using different
experimental conditions: acid concentrations between 15-23 per cent HCl, the
temperature range of 70-90 degrees C, with stoichiometric ratio between reactants
and with acid excess, the extraction time being up to 180 min. In optimum
conditions, the magnesium extraction is almost total (99.5 per cent). A well
balanced processing of these serpentinites looks for both the silica residue
utilization and the chloride solutions, in order to separate the prevalent
magnesium as well as the valuable microcomponents--nickel and cobalt.
PMID- 11008922
TI - Predictors of inactivation and reasons for participant inactivation during a skin
cancer chemoprevention study.
AB - Maintaining good compliance is a major challenge in long-term cancer
chemoprevention trials. Minimizing the number of inactive participants during a
trial is an important factor in maximizing compliance. Identifying reasons for
and predictors of inactivation is the first step in being able to reduce
participant inactivation. In this skin cancer chemoprevention trial, the 2,297
participants were randomized to receive 25,000 IU of retinol daily or a placebo.
Median follow-up time was 3.8 years. The reason for inactivation was determined
for each participant who stopped taking the study capsules. Six hundred and
seventy-seven (29.7%) participants became inactive during the 5-year study. There
was no significant difference between the number of participants inactivating by
treatment group or sex. The most common reasons for inactivation were illness of
subject, spouse, or a close relative (18.6%) and experience of a clinical symptom
consistent with vitamin A ingestion (17.1%). Participants in the vitamin A group
(10.1%) more frequently cited symptoms coded as "not consistent with vitamin A"
as the reason for inactivation compared with those in the placebo group [5.4% (P
< 0.05)]. The inactivation rate was highest in the first month of the trial and
declined thereafter. A low education level (hazard ratio, 1.59) and unmarried
status (hazard ratio, 1.29) were the only significant predictors of inactivation.
These findings may be useful in developing targeted strategies to decrease
inactivation and thereby increase compliance in future chemoprevention trials.
However, these findings need to be confirmed because published research in this
area is very limited.
PMID- 11008924
TI - Association effects of vitamin B6 and various magnesium salts on a
pharmacological model: the human amniotic membrane.
AB - The effects of the association of vitamin B6 and Mg salts: aspartate, citrate,
lactate, pidolate, sulfate, were studied on the ionic transfer through a
membraneous pharmacological model: the isolated human amniotic membrane. The
ionic transfer was evaluated by measure of the total conductance in the maternal
to fetal way (GtM) and in the fetal to maternal way (GtF), of the ionic fluxes
(F1 on the maternal side, F2 on the fetal side) and of the ratio F1/F2. The
results were explained in terms of monophasic (decrease: screening or increase:
binding interactions with the polar surface moities) or biphasic (decrease then
increase) action. The results indicated: Mg aspartate decreased GtF, F1, F2
whatever concentration and had a concentration-dependent effect on GtM, F1/F2.
The addition of vitamin B6 induced a new concentration-dependent effect (biphasic
action: decrease then increase) on GtF, F1 and also modified F2, F1/F2. Mg
citrate decreased GtM, GtF, F2 whatever the concentration and had a concentration
dependent effect on F1, F1/F2. The addition of vitamin B6 induced a new biphasic
effect on GtM and GtF. Mg lactate decreased GtM, F1, F2, F1/F2 whatever the
concentration but had a concentration-dependent effect on GtF. The addition of
vitamin B6 induced a new biphasic effect on GtM, F1, F2, F1/F2. Mg pidolate had
no effect on GtM, GtF, F2, F1/F2 and decreased F1. The addition of vitamin B6 did
not induce variation. Mg sulfate had no effect on GtM, increased GtF and
decreased F1, F2, F1/F2. The addition of vitamin B6 induced a new concentration
dependent effect on F2. The association between vitamin B6 and Mg salts
implicated a new action on components of the amniotic ionic transfer
characterized by a biphasic action (decrease then increase concentration
dependent effect). This effect was dependent on the anion associated with
magnesium. The magnesium salts may be classified with regard to the beneficial
effect due to the association with vitamin B6 in the following decreasing order:
aspartate and lactate, citrate, pidolate, sulfate.
PMID- 11008925
TI - Importance of decreased intracellular phosphate and magnesium concentrations and
reduced ATPase activities in spontaneously hypertensive rats.
AB - A decrease in total magnesium content is not a direct proof of a decreased
magnesium ion concentration. It could reflect a phosphate alteration or an ATP
metabolism disorder. Plasma phosphate levels are lower in spontaneously
hypertensive rats (SHRs) than in Wistar-Kyoto (WKY) rats, and defects in membrane
regulation or mitochondrial ATP synthase occur. Only sparse data exist concerning
cellular magnesium and phosphate concentrations in hypertensive cells. In aortic
smooth muscle cells from 10 SHRs of the Munster strain and 10 age-matched
normotensive WKY rats, the intracellular phosphate and magnesium content was
measured by electron probe X-ray microanalysis (Camscan CS 24 apparatus,
Cambridge, U.K.). The Mg++ content was 0.90+/-0.15 g/kg dry weight in SHRs versus
1.15+/-0.10 g/kg dry weight in WKY rats (p<0.05). Vascular smooth muscle
phosphate content was 23.6+/-0.79 g/kg dry weight in WKY rats versus 15.81+/-1.22
g/kg dryweight in SHRs (p<0.01). In seven animals, erythrocytic ATP content was
180.2+/-102 in SHRs vs. 432+/-72 micromol/L cells in WKY rats (p< 0.01). The
Na+/K+-ATPase activity was significantly decreased in hypertensive animals as
compared to controls (6.49+/-2.3 vs. 12.64+/-2.9 nmol inorganic phosphate/mg
protein/min (p< 0.01)). Aortic smooth muscle cells from SHRs are characterized by
markedly lowered cellular phosphate and magnesium concentrations and an altered
ATP metabolism, possibly due to a membrane defect or a magnesium deficit in
hypertensive cells.
PMID- 11008926
TI - Disturbances of magnesium concentrations in various brain areas in Alzheimer's
disease.
AB - Our first project aimed at the determination of the average values of Mg in
normal human brain (20 individuals, mean age 70 years). Ten brain parts were
selected from both hemispheres. Determinations were carried out by inductively
coupled plasma atomic emission spectrometry, inductively coupled plasma mass
spectrometry and instrumental neutron activation analysis methods. In order to
investigate the precision and the accuracy of the methods five biological
standard reference materials were analyzed. The present results show a non
homogeneous distribution of Mg in normal human brain. Regions corresponding to
each other in both hemispheres show almost identical concentration. The second
goal was to study the possible Mg concentration changes in Alzheimer's disease
(nine patients, ten brain parts). Mg values are found to be significantly
decreased in brain regions of diseased patients compared to the controls.
PMID- 11008927
TI - Are low magnesium levels in type 1 diabetes associated with electromyographical
signs of polyneuropathy?
AB - OBJECTIVE: Our aim was to study the relationship between the magnesium status in
type 1 diabetic patients and disturbances in nerve conduction velocity.
Furthermore we wanted to investigate whether repletion of magnesium depletion
could improve the decreased nerve conduction velocity measurements. In a cross
sectional study, 154 type 1 diabetic patients were screened for their erythrocyte
magnesium content and an electrophysiological measurement of the peripheral
nervous system was carried out. In a subsequent intervention study, out of this
screened population, 23 type 1 patients, with disturbed nerve conduction velocity
measurements and low erythrocyte magnesium levels [< 2.3 mmol/L) were given oral
magnesium supplements, during 1 year. Twenty type 1 patients with identical
characteristics served as controls. In the cross-sectional study disturbed nerve
conduction velocities were found in the older patients, in patients with a longer
duration of diabetes and a worse metabolic control. EMG polyneuropathy signs were
significantly more frequent in diabetic patients with low erythrocyte Mg. The
intervention study demonstrated that under unchanged metabolic control,
supplementation with magnesium could improve nerve conduction, especially in
younger patients with a shorter duration of diabetes. Erythrocyte Mg was lower in
type 1 diabetic patients with polyneuropathy. Mg supplementation increasing Mg
RBC might (possibly?) improve nerve conduction measured by electromyography at
least in younger patients with a short duration of diabetes and presenting early
signs of the neurological complication.
PMID- 11008928
TI - A review of the status of magnesium and related minerals in the sudden infant
death syndrome (SIDS).
AB - Sudden infant death syndrome (SIDS) is the sudden death of an infant under 1 year
of age that remains unexplained after a thorough case investigation, including
performance of a complete autopsy. Despite recent reductions in the SIDS rate
attributed to placing the baby to sleep on his back, SIDS remains the most common
cause of infant mortality between 1 month and 1 year of age in developed
countries. This review concerns the current state of a hypothesis (1972) that
magnesium deficiency, which causes sudden death in young mammals, is the major
cause of SIDS. Numerous investigators have compared the concentration of
magnesium, and other minerals from soft tissues and bone in SIDS with non-SIDS
controls (normal infants who died suddenly of known cause such as trauma).
Because of rapid shifts of minerals during early development, SIDS and control
infants must be matched for gestational and postnatal age. About 95 per cent of
SIDS occurs between 1-6 months of life, with peak incidence at 2-4 months, when
vitreous magnesium is high. There is little change in magnesium in the relatively
inert vitreous despite extremes in dietary magnesium. All values fall within a
small range, with scatter. Magnesium rapidly increases in foetal cartilage with
ossification of the bone. Early in magnesium deficiency, liver magnesium may be
increased or unchanged, but it does not increase during magnesium excess. Lead
accumulation is increased in magnesium deficiency. Among infants with high
environmental exposure to lead, those who die of SIDS rather than non-SIDS
infants have the greater lead burden. Soft water with low magnesium and calcium
and with high concentration of sodium have been linked to higher SIDS rates,
which have been attributed to low magnesium. It is concluded that the SIDS
hypothesis has neither been proved nor disproved.
PMID- 11008929
TI - The Windscale accident--some memories and reflections.
PMID- 11008930
TI - Epidemiological studies of the Sellafield workforce.
PMID- 11008931
TI - Mortality and cancer registration experience of the Sellafield employees known to
have been involved in the 1957 Windscale accident.
AB - The mortality and cancer morbidity experience of the 470 male Sellafield
employees known to be involved in the 1957 Windscale accident is reported. All
these employees are known to have been involved in dealing with the fire itself,
or in the clean-up operation afterwards. The size of the study population is
small, leading to predicted low power to reveal any effects, but the cohort is of
interest because of the involvement of the workers in the accident. For 1957-97,
using rates for England and Wales to calculate the expected numbers, the all
causes standardised mortality ratio (SMR) is 100 (observed = 258, expected =
258.80), and the all malignant neoplasms SMR is 79 (observed = 58, expected =
73.12) which is not significantly different from 100. For 1971-91, the all
malignant neoplasms standardised registration ratio (SRR) of 85 (observed = 59,
expected = 69.23) is not significantly different from 100. Significant excesses
of deaths from diseases of the circulatory system (SMR = 121) and from ischaemic
heart disease (SMR = 128), and a significant deficit of deaths from cancer of the
genito-urinary organs (SMR = 31), were found. There were no significant
differences in mortality rates between workers who had received high recorded
external doses during the fire and those who had received low doses, though the
power of this comparison was low. Comparison of the mortality rates of workers
directly involved in the accident with workers in post, but not so involved,
showed no significant differences. This study has been unable to detect any
effect of the 1957 fire upon the mortality and cancer morbidity experience of
those workers involved in it.
PMID- 11008932
TI - The assessment of organ doses from plutonium for an epidemiological study of the
Sellafield workforce.
AB - An epidemiological study of mortality and cancer rates in plutonium workers at
the Sellafield nuclear installation has been carried out by researchers at the
London School of Hygiene and Tropical Medicine. The study required the assessment
of organ-specific doses from plutonium for more than 5000 workers over a period
of 40 years. This was a major undertaking as it involved the reconstruction of
annual received doses from the results of some 223,000 urine samples that had
been provided by the workers in the study. This paper outlines the techniques and
strategies adopted in order to generate best estimates of dose from the available
data, and presents summaries of these doses.
PMID- 11008933
TI - An optical method for three-dimensional dosimetry.
AB - Accurate determination of the spatial distribution of the absorbed dose of
ionising radiation plays an important role in radiotherapy, industrial radiation
processing and many other applications. Computer calculations have frequently
been used to estimate three-dimensional (3D) dose distributions in complex
geometries and it becomes important to validate these by accurate 3D
measurements. For this purpose we have been investigating the use of gelatin gels
loaded with a modified Fricke solution which are pale orange in appearance and
which, upon irradiation, become increasingly purple when viewed in normal light.
This ferrous sulphate xylenol orange in gelatin gel (FXG) system displays very
good properties, such as sensitivity, linearity and dynamic range, that make it
suitable for 3D dosimetry applications. A high-speed optical tomography readout
technique has been developed enabling two-dimensional projections of optical
absorption data to be recorded rapidly. From these data the 3D absorbed dose
distribution can quickly be derived with minimal degradation due to ion
diffusion.
PMID- 11008934
TI - Prominent artificial radionuclide activity in the environment of coastal
Karnataka on the southwest coast of India.
AB - Studies on radiation level and radionuclide distribution in the environment of
coastal Karnataka were undertaken to provide baseline data for the future
assessment of the impact of the nuclear and thermal power stations that are being
set up in the region and to understand the behaviour of radionuclides in the
environment. As part of the programme the concentrations of two important
artificial radionuclides, namely 90Sr and 137Cs, have been measured in a number
of environmental samples. The concentration of 90Sr is very low in most of the
samples. Among the samples analysed for the concentration of 137Cs, soil samples
showed elevated levels of activity in some sampling stations. Among the
vegetables, brinjal (Solanum melongena. L) showed considerable activity. The
internal dose due to intake of 90Sr through diet was 0.42 microSv year(-1) for
the vegetarian population and 0.32 microSv year(-1) for the non-vegetarian
population. The internal dose due to dietary intake of 137Cs was found to be 0.34
microSv year(-1) and 0.26 microSv year(-1) respectively for the vegetarian and
non-vegetarian population. The results are discussed in the light of the
literature values reported for other environs of India and abroad and appropriate
inferences are drawn.
PMID- 11008935
TI - Contaminated land liability issues: legal perspective.
AB - Until recently, companies that contaminated land faced little prospect of being
prosecuted or having claims made against them for any personal injuries or
property damage arising from the contamination. Most companies would have
considered it to be inconceivable that they could be required to clean up
contamination resulting from an historic disposal, particularly if the disposal
had been neither negligent nor unlawful. Current environmental law differs
significantly, however, from the law which existed even 10 years ago. This paper
examines liabilities arising from contaminated land. First, it discusses the new
contaminated land regime and a parallel regime to remediate sites that are
contaminated with radioactive substances. Second, it discusses remediation
liabilities for water pollution. Such liabilities may well involve the
remediation of contaminated land when groundwater is polluted. Finally, the paper
examines liabilities for property damage and personal injuries arising from
contamination by radioactive substances.
PMID- 11008936
TI - Application of regulations to cosmetic lasers in private practice.
AB - Recent years have seen a growth in the number of non-NHS premises, for example
beauty salons, offering cosmetic laser treatments such as laser hair removal. By
law, such practices are subject to registration and monitoring by Health
Authorities. However, a national consensus on appropriate standards is urgently
required, particularly on interpretation of the legal requirements for medical
direction and operator training, in order to ensure consistency of standards in
private practice with lasers across the country. This paper outlines the
difficulties experienced in the inspection and registration process, and makes
recommendations on appropriate interim standards, pending formal guidance from
professional bodies and the promulgation of revised regulations. Until such
guidance is in place, it may be wise for Health Authorities to include within
their inspection protocols a requirement that applicants for laser registrations
produce a statement as to the exact form which medical direction of laser
treatment will take, to enable the Health Authority to consider and take advice
on its suitability. Similarly a requirement that laser operators are state
registered health professionals will ensure that these potentially hazardous
devices are only used by properly qualified operators, whilst professional bodies
work towards a consensus on minimum training standards.
PMID- 11008937
TI - Stillbirths and male irradiation.
PMID- 11008938
TI - On collective dose.
PMID- 11008939
TI - The 'controllable dose' debate: results of the IRPA consultation exercise.
PMID- 11008940
TI - Study of childhood cancer and paternal preconceptional irradiation at USA nuclear
facilities.
PMID- 11008941
TI - Japanese atomic bomb survivors.
PMID- 11008942
TI - SRP meeting: Surface and airborne contamination. AWE Aldermaston, 26-27 June
2000.
PMID- 11008943
TI - Conference on medical physics and its applications. Zarka-Jordan, 24-26 April
2000.
PMID- 11008944
TI - Commentary: the controversy between the IAEA Code of Practice and the TG-51
protocol.
PMID- 11008945
TI - Power frequency electromagnetic fields and health. Where's the evidence?
AB - Twenty years ago concerns were raised that exposure to power frequency (or
extremely low frequency (ELF)) electromagnetic fields (EMFs) may be associated
with an increased risk of cancer or other health hazards. Subsequently no
associations have been shown between laboratory magnetic field exposures and
carcinogenesis in either animal or cellular models. Indeed, studies have
demonstrated that magnetic fields are not associated with cancer. However, the
puzzle remains that the results of some epidemiological studies may be
interpreted as suggesting that living close to high-voltage transmission (HVT)
lines appears to increase slightly the risk of childhood leukaemia.
Alternatively, these results could result from small biases and errors in
individual studies, which might not necessarily be the same in each study. The
nature of the epidemiological studies (power-line, wire code, magnetic field or
appliance based) appears to determine whether and how the EMFs associated with
HVT lines might be a risk factor. It is possible that a simple association with
either magnetic or electric field exposure may not be the whole answer, and an
alternative mechanism is always a possibility. Although the interpretation of the
available evidence by most expert bodies has led them to conclude that exposure
to power frequency electric and magnetic fields is not a human health hazard, a
working group under the auspices of the US National Institute of Environmental
Health Sciences (NIEHS) concluded that there was a possible low risk associated
with certain exposures to ELF magnetic fields. NIEHS itself interpreted the
finding as insufficient to warrant aggressive regulatory concern but stated that,
because virtually everyone is routinely exposed to ELF EMFs, passive regulatory
action is warranted, such as a continued emphasis on educating both the public
and the regulated community on means aimed at reducing exposures. These analyses,
conclusions and advice are not contradicted by subsequent studies, and therefore
the conclusion of the World Health Organisation that further research is needed
seems valid.
PMID- 11008946
TI - A comparison between calculated and experimental kQ photon beam quality
correction factors.
AB - To validate the calculated values of kQ for high-energy photon beams given in the
International Code of Practice for radiotherapy dosimetry based on water-absorbed
dose standards, a comparison with experimental values derived in standards
laboratories and in clinical beams has been made. The study includes a
compilation of experimental values for ionization chambers of the type
NE2561/2611, NE2571, PTW30001 and PR06. The energy dependence of the G(Fe3+)
ratio of high-energy x-rays to 60Co gamma-rays by Klassen et al is taken into
account for all the Fricke-derived values. For three of the chamber types
analysed, the comparison shows that the calculated values are a very good
estimate of the average values of kQ in the entire range of photon beam qualities
available for clinical use. For the NE2571 chamber type a difference which
increases with energy between calculated and experimental kQ factors has been
observed; however, the largest difference with a fit describing the entire set of
experimental data is always smaller than 0.4%. It is concluded that if the
recommendation of the Code of Practice for an individual calibration of the
user's chamber at a range of photon beam qualities is not available, the use of
calculated kQ factors will yield absorbed dose to water determinations accurate
within the uncertainty limits of the majority of experimental data available. The
good agreement between calculated and measured values, obtained for practically
all the experimental data using TPR(20,10) as photon beam quality specifier, is
not satisfied in some cases for two high-energy soft beams used at the Canadian
NRC. There appears to be no justification for a change to a different photon beam
quality specifier solely on the grounds that such a limited set of data is not
described by the same distributions as the rest of the experimental data.
PMID- 11008947
TI - First human transvenous coronary angiography at the European Synchrotron
Radiation Facility.
AB - The first operation of the European Synchrotron Radiation Facility (ESRF) medical
beamline is reported in this paper. The goal of the angiography project is to
develop a reduced risk imaging technique, which can be used to follow up patients
after coronary intervention. After the intravenous injection of a contrast agent
(iodine) two images are produced with monochromatic beams, bracketing the iodine
K-edge. The logarithmic subtraction of the two measurements results in an iodine
enhanced image, which can be precisely quantified. A research protocol has been
designed to evaluate the performances of this method in comparison with the
conventional technique. Patients included in the protocol have previously
undergone angioplasty. If a re-stenosis is suspected, the patient is imaged both
at the ESRF and at the hospital with the conventional technique, within the next
few days. This paper reports the results obtained with the first patients. To
date, eight patients have been imaged and excellent image quality was obtained.
PMID- 11008948
TI - IPEM guidelines on dosimeter systems for use as transfer instruments between the
UK primary dosimetry standards laboratory (NPL) and radiotherapy centres.
AB - United Kingdom dosimetry codes of practice have traditionally specified one
electrometer for use as a secondary standard, namely the Nuclear Enterprises (NE)
2560 NPL secondary standard therapy level exposure meter. The NE2560 will become
obsolete in the foreseeable future. This report provides guidelines to assist
physicists following the United Kingdom dosimetry codes of practice in the
selection of an electrometer to replace the NE2560 when necessary. Using an
internationally accepted standard (BS EN 60731:1997) as a basis, estimated error
analyses demonstrate that the uncertainty (one standard deviation) in a charge
measurement associated with the NE2560 alone is approximately 0.3% under
specified conditions. Following a review of manufacturers' literature, it is
considered that modern electrometers should be capable of equalling this
performance. Additional constructural and operational requirements not specified
in the international standard but considered essential in a modern electrometer
to be used as a secondary standard are presented.
PMID- 11008949
TI - Comparison of conformal radiation therapy techniques within the dynamic
radiotherapy project 'Dynarad'.
AB - The objective of the dynamic radiotherapy project 'Dynarad' within the European
Community has been to compare and grade treatment techniques that are currently
applied or being developed at the participating institutions. Cervical cancer was
selected as the tumour site on the grounds that the involved organs at risk,
mainly the rectum and the bladder, are very close to the tumour and partly
located inside the internal target volume. In this work, a solid phantom
simulating the pelvic anatomy was used by institutions in Belgium, France,
Greece, Holland, Italy, Sweden and the United Kingdom. The results were evaluated
using both biological and physical criteria. The main purpose of this parallel
evaluation is to test the value of biological and physical evaluations in
comparing treatment techniques. It is demonstrated that the biological objective
functions allow a much higher conformality and a more clinically relevant scoring
of the outcome. Often external beam treatment techniques have to be combined with
intracavitary therapy to give clinically acceptable results. However, recent
developments can reduce or even eliminate this need by delivering more conformal
dose distributions using intensity modulated external dose delivery. In these
cases the reliability of the patient set-up procedure becomes critical for the
effectiveness of the treatment.
PMID- 11008950
TI - Monte Carlo verification of IMRT dose distributions from a commercial treatment
planning optimization system.
AB - The purpose of this work was to use Monte Carlo simulations to verify the
accuracy of the dose distributions from a commercial treatment planning
optimization system (Corvus, Nomos Corp., Sewickley, PA) for intensity-modulated
radiotherapy (IMRT). A Monte Carlo treatment planning system has been implemented
clinically to improve and verify the accuracy of radiotherapy dose calculations.
Further modifications to the system were made to compute the dose in a patient
for multiple fixed-gantry IMRT fields. The dose distributions in the experimental
phantoms and in the patients were calculated and used to verify the optimized
treatment plans generated by the Corvus system. The Monte Carlo calculated IMRT
dose distributions agreed with the measurements to within 2% of the maximum dose
for all the beam energies and field sizes for both the homogeneous and
heterogeneous phantoms. The dose distributions predicted by the Corvus system,
which employs a finite-size pencil beam (FSPB) algorithm, agreed with the Monte
Carlo simulations and measurements to within 4% in a cylindrical water phantom
with various hypothetical target shapes. Discrepancies of more than 5% (relative
to the prescribed target dose) in the target region and over 20% in the critical
structures were found in some IMRT patient calculations. The FSPB algorithm as
implemented in the Corvus system is adequate for homogeneous phantoms (such as
prostate) but may result in significant under or over-estimation of the dose in
some cases involving heterogeneities such as the air-tissue, lung-tissue and
tissue-bone interfaces.
PMID- 11008951
TI - Monte Carlo simulation of dose distributions from a synchrotron-produced
microplanar beam array using the EGS4 code system.
AB - Microbeam therapy is established as a general concept for brain tumour treatment.
A synchrotron based x-ray source was chosen for experimental research into
microbeam therapy, and therefore new simulations were essential for investigating
the therapy parameters with a proper description of the synchrotron radiation
characteristics. To design therapy parameters for tumour treatments, the newly
upgraded LSCAT (Low energy SCATtering) package of the EGS4 Monte Carlo simulation
code was adapted to develop an accurate self-written user code for calculating
microbeam radiation dose profiles with a precision of 1 microm. LSCAT is highly
suited to this purpose due to its ability to simulate low-energy x-ray transport
with detailed photon interactions (including bound electron incoherent scattering
functions, and linear polarized coherent scattering). The properties of the
synchrotron x-ray microbeam, including its polarization, source spectrum and beam
penumbra, were simulated by the new user codes. Two concentric spheres, an inner
sphere, defined as a brain, and a surrounding sphere, defined as a skull,
represented the phantom. The microbeam simulation was tested using a 3 x 3 cm
array beam for small treatment areas and a 6 x 6 cm array for larger ones, with
different therapy parameters, such as beam width and spacing. The results showed
that the microbeam array retained an adequate peak-to-valley ratio, of five times
at least, at tissue depths suitable for radiation therapy. Dose measurements
taken at 1 microm resolution with an 'edge-on' MOSFET validated the basics of the
user code for microplanar radiation therapy.
PMID- 11008952
TI - Wall correction factors for calibration of plane-parallel ionization chambers
with high-energy photon beams.
AB - Most dosimetry protocols recommend that calibration of plane-parallel ionization
chambers be performed in an electron beam of sufficiently high energy by
comparison with cylindrical chambers. For various plane-parallel chambers, the
1997 IAEA TRS-381 protocol includes an overall perturbation factor pQ for
electron beams, a wall correction factor p(wall) for a 60Co beam and the product
of two wall corrections k(att)k(m) for 60Co in-air calibration. The recommended
values of p(wall) for plane-parallel chambers, however, are limited to certain
phantom materials and a 60Co beam, and are not given for other phantom materials
and x-ray beams. In this work, the p(wall) values of the commercially available
NACP, PTW/Markus and PTW/Roos plane-parallel chambers in a solid water phantom
have been determined with 60Co and 4 and 10 MV photon beams. The k(att)k(m)
values for the NACP and PTW/Markus chambers have also been obtained. The wall
correction factors p(wall) and k(att)k(m) have been determined by intercomparison
with a calibrated Farmer chamber. The average value of p(wall) for these plane
parallel chambers was 1.005 +/- 0.1% (1 SD) for 60Co beams and 1.007 +/- 0.2% (1
SD) for both 4 MV and 10 MV photons. The k(att)k(m) values for the NACP and
PTW/Markus chambers were about 1.5% lower than other published data.
PMID- 11008953
TI - The value of the PinPoint ion chamber for characterization of small field
segments used in intensity-modulated radiotherapy.
AB - Volume averaging and lack of electronic equilibrium complicate accurate dosimetry
of small photon fields. In this paper the performance of the PinPoint ion chamber
for characterizing small fields used in intensity-modulated radiotherapy (IMRT)
was investigated and the results were compared with those obtained using the
Markus ion chamber and a diamond detector. Sharp beam penumbras were measured for
a 5 x 5 cm field defined using a cerrobend block mounted on the accelerator head.
In addition, output factors were measured for a 6 MV photon beam and a variety of
small rectangular fields collimated widthwise using the multileaf collimator
(MLC) in combination with the back-up jaws. From this study, a reference field of
5 x 5 cm and a measuring depth of 5 cm are recommended. This is related to the
over-response of the PinPoint chamber to low-energy Compton scattered photons, an
effect that was investigated rigorously and turned out to limit the scope of this
ionization chamber. However, taking into account some limitations, the PinPoint
chamber is an excellent detector for output measurements in small fields down to
2 cm. In profile measurements the chamber causes a broadening of the measured
penumbras but its spatial resolution is superior to that of the Markus chamber.
PMID- 11008954
TI - Theoretical considerations to the verification of dynamic multileaf collimated
fields with a SLIC-type portal image detector.
AB - The verification possibilities of dynamically collimated treatment beams with a
scanning liquid ionization chamber electronic portal image device (SLIC-EPID) are
investigated. The ion concentration in the liquid of a SLIC-EPID and therefore
the read-out signal is determined by two parameters of a differential equation
describing the creation and recombination of the ions. Due to the form of this
equation, the portal image detector describes a nonlinear dynamic system with
memory. In this work, the parameters of the differential equation were
experimentally determined for the particular chamber in use and for an incident
open 6 MV photon beam. The mathematical description of the ion concentration was
then used to predict portal images of intensity-modulated photon beams produced
by a dynamic delivery technique, the sliding window approach. Due to the nature
of the differential equation, a mathematical condition for 'reliable leaf motion
verification' in the sliding window technique can be formulated. It is shown that
the time constants for both formation and decay of the equilibrium concentration
in the chamber is in the order of seconds. In order to guarantee reliable leaf
motion verification, these time constants impose a constraint on the rapidity of
the image-read out for a given maximum leaf speed. For a leaf speed of 2 cm s(
1), a minimum image acquisition frequency of about 2 Hz is required. Current SLIC
EPID systems are usually too slow since they need about a second to acquire a
portal image. However, if the condition is fulfilled, the memory property of the
system can be used to reconstruct the leaf motion. It is shown that a simple edge
detecting algorithm can be employed to determine the leaf positions. The method
is also very robust against image noise.
PMID- 11008955
TI - Selection and determination of beam weights based on genetic algorithms for
conformal radiotherapy treatment planning.
AB - A genetic algorithm has been used to optimize the selection of beam weights for
external beam three-dimensional conformal radiotherapy treatment planning. A
fitness function is defined, which includes a difference function to achieve a
least-square fit to doses at preselected points in a planning target volume, and
a penalty item to constrain the maximum allowable doses delivered to critical
organs. Adjustment between the dose uniformity within the target volume and the
dose constraint to the critical structures can be achieved by varying the beam
weight variables in the fitness function. A floating-point encoding schema and
several operators, like uniform crossover, arithmetical crossover, geometrical
crossover, Gaussian mutation and uniform mutation, have been used to evolve the
population. Three different cases were used to verify the correctness of the
algorithm and quality assessment based on dose-volume histograms and three
dimensional dose distributions were given. The results indicate that the genetic
algorithm presented here has considerable potential.
PMID- 11008956
TI - Polymer gel dosimetry using x-ray computed tomography: a feasibility study.
AB - A new three-dimensional dosimetry technique using x-ray computed tomography (CT)
to analyse polymer gels is proposed. The CT imaging is sensitive to radiation
induced density changes that occur within irradiated polyacrylamide gel (PAG). In
this preliminary study, a CT imaging protocol is developed to optimize CT images
of PAG; the response of PAG CT number to dose (N(CT)-dose response) and the
reproducibility of the response are investigated, and the use of CT to analyse
PAG is compared with MRI. Experiments were conducted using two 1.5 l cylindrical
PAG phantoms (3% acrylamide, 3% bis and 5% gelatin by weight), one irradiated
with four intersecting 10 MV photon beams and the other with 10 sets of 6 MV
parallel opposed circular radiosurgery fields. The final imaging protocol
involves using optimum CT parameters (120 kVp and 200 mAs for our GE HiSpeed CT/i
scanner), image averaging and background subtraction. The N(CT)-dose response is
reproducible, linear up to 800-1000 cGy and is relatively insensitive to the gel
temperature during imaging. The dose resolution is approximately 50 cGy for an
image thickness of 10 mm. Despite the low dose resolution, preliminary results
indicate that this CT technique provides accurate localization of high dose
gradients such as those observed in stereotactic radiosurgery. Thus, given the
availability and speed of CT scanners, the technique has the potential to be a
valuable and practical 3D dose verification tool in radiation therapy.
PMID- 11008957
TI - General characteristics of the use of silicon diode detectors for clinical
dosimetry in proton beams.
AB - The properties of silicon diode detectors, used for dosimetry in clinical proton
beams, were investigated with special regard to the measurement of relative dose
distributions in water. Different types of silicon diode detector were studied,
and the resulting distributions of detector signal versus depth in the water
phantom were compared with the corresponding distributions obtained with a plane
parallel NACP ionization chamber. The measurements were performed in a proton
beam with an initial energy of 173 MeV. It is shown that the Hi-p silicon
detector gives a signal which is proportional to the ionization density in the
silicon crystal in all parts of the Bragg curve, and for all levels of
accumulated dose to the detector. This is in contrast to detectors based on n
type silicon, or on low resistivity p-type silicon. After pre-irradiation, these
latter detectors show a stopping-power dependent recombination, yielding an
increase in the detector signal per unit dose with increasing LET. This effect
leads to an over-response in the Bragg peak, which increases gradually with the
accumulated detector dose. Using the Hi-p silicon diode detector, the depth
ionization distribution was found to be equal to the distribution obtained with
the plane-parallel NACP ionization chamber at all pre-irradiation levels, within
the experimental accuracy. This implies that the quotient between the ionization
in the detector and the absorbed dose to the surrounding water is equal for these
detectors.
PMID- 11008958
TI - The development of a phantom to determine foetal organ doses from 131I in the
foetal thyroid.
AB - Iodine can accumulate in the foetal thyroid from the twelfth week of gestation
onwards. If the iodine taken up by the foetal thyroid is in the form of 131I then
the thyroid and its proximal tissues and organs will be irradiated. Several
mathematical models exist in the literature on foetal/maternal iodine kinetics.
However, very few studies have been performed where the foetal thyroid had been
physically modelled thus allowing the determination of foetal organ dosimetry
from 131I in the foetal thyroid. Here, the development of such a physical model
or phantom is described and dosimetry results obtained from the phantom are
discussed. The phantom is of Perspex construction, the dimensions of which are
sufficient to incorporate models of the foetus at 16, 24 and 36 weeks'
gestational age. The dosimetry of two organs is presented, that of the brain and
the thymus. The results show that the measured absorbed dose is comparable with
that calculated using modified MIRD dosimetry and traditional methods. The
results also show that the dose to the thymus is greater than that of the brain
by a factor of almost 30 for 16 weeks' gestational age.
PMID- 11008959
TI - A comparison of quantitative measures of arterial tortuosity using sine wave
simulations and 3D wire models.
AB - This paper discusses the quantitative measurement of arterial tortuosity. The
measures described are a tortuosity coefficient, TC, based on the second
derivative of the vessel midline and the distance factor, DF, defined as L/D - 1,
where L is the vessel length and D is the straight line distance between the
vessel end points. A tortuosity scale derived from sine wave simulations was used
to determine the ability of these two measures to quantify tortuosity. The
tortuosity coefficient was demonstrated to be an appropriate measure whilst the
distance factor was found to be a measure of vessel elongation rather than
tortuosity. A tomographic method of deriving three-dimensional measures of TC and
DF is described using a wire model. The x, y coordinates along the length of the
wire were obtained from CT slices and the three-dimensional values calculated as
the geometric mean of the TC and DF values measured in the x and y directions.
Rotation of the wire through 90 degrees demonstrated that the three-dimensional
derivations of TC and DF were independent of the orientation of the wire.
PMID- 11008960
TI - Physical characteristics of the ECAT EXACT3D positron tomograph.
AB - The 'EXACT3D' positron tomograph, which is now in routine clinical research use,
was developed with the aim of achieving unprecedented sensitivity, high spatial
and temporal resolution and simplicity of design using proven detector
technology. It consists of six rings of standard detector blocks (CTI/Siemens
EXACT HR+) with 4.39 mm x 4.05 mm x 30 mm elements, giving an axial field of view
(FOV) of 23.4 cm. This extended FOV and the absence of interplane septa and
retractable transmission rod sources has allowed greatly simplified gantry and
detector cassette design. Operation in exclusive 3D mode requires an alternative
to the conventional coincidence method for transmission scanning, and a single
photon approach using a hydraulically driven 137Cs point source has been
implemented. The tomograph has no other moving parts. A single time frame of data
without any compression is very large (> 300 Mbyte) and two approaches are
employed to overcome this difficulty: (a) adjacent sinograms can be summed
automatically into different combinations and (b) listmode (event-by-event)
acquisition has been instituted, which is both storage efficient (particularly
for acquisition of sparse data sets) and maximizes temporal resolution. The high
speed I/O and computing hardware can maintain a sustained acquisition rate of
about 4 million coincidence events per second. A disadvantage of the large axial
FOV in 3D is the increased sensitivity to activity outside the coincidence FOV.
However, this can be minimized by additional side shielding. The mean spatial
resolution is 4.8 +/- 0.2 mm FWHM (transaxial, 1 cm off-axis) and 5.6 +/- 0.5 mm
(axial, on-axis). Its absolute efficiency is 5.8% for a line source in air (just
spanning the axial FOV) and 10% for a central point source (with thresholds of
350-650 keV). For a uniform 20 cm diameter cylinder, the efficiency is 69 kcps
kBq(-1) ml(-1) (after subtraction of a scatter fraction of 42%). Sensitivity
relative to the EXACT HR+ (with four rings of blocks) is 2.5 (3D) and 12 (2D)
times respectively. The rate of random events in blood flow studies in the brain
and body, using 15O-labelled water, can be controlled by limiting the
administered dose and inserting additional side shielding.
PMID- 11008961
TI - Factor analysis with a priori knowledge--application in dynamic cardiac SPECT.
AB - Two factor analysis of dynamic structures (FADS) methods for the extraction of
time-activity curves (TACs) from cardiac dynamic SPECT data sequences were
investigated. One method was based on a least squares (LS) approach which was
subject to positivity constraints. The other method was the well known apex
seeking (AS) method. A post-processing step utilizing a priori information was
employed to correct for the non-uniqueness of the FADS solution. These methods
were used to extract 99mTc-teboroxime TACs from computer simulations and from
experimental canine and patient studies. In computer simulations, the LS and AS
methods, which are completely different algorithms, yielded very similar and
accurate results after application of the correction for non-uniqueness. FADS
obtained blood curves correlated well with curves derived from region of interest
(ROI) measurements in the experimental studies. The results indicate that the
factor analysis techniques can be used for semi-automatic estimation of activity
curves derived from cardiac dynamic SPECT images, and that they can be used for
separation of physiologically different regions in dynamic cardiac SPECT studies.
PMID- 11008962
TI - A filtering approach to image reconstruction in 3D SPECT.
AB - We present a new approach to three-dimensional (3D) image reconstruction using
analytical inversion of the exponential divergent beam transform, which can serve
as a mathematical model for cone-beam 3D SPECT imaging. We apply a circular cone
beam scan and assume constant attenuation inside a convex area with a known
boundary, which is satisfactory in brain imaging. The reconstruction problem is
reduced to an image restoration problem characterized by a shift-variant point
spread function which is given analytically. The method requires two computation
steps: backprojection and filtering. The modulation transfer function (MTF) of
the filter is derived by means of an original methodology using the 2D Laplace
transform. The filter is implemented in the frequency domain and requires 2D
Fourier transform of transverse slices. In order to obtain a shift-invariant cone
beam projection-backprojection operator we resort to an approximation, assuming
that the collimator has a relatively large focal length. Nevertheless, numerical
experiments demonstrate surprisingly good results for detectors with relatively
short focal lengths. The use of a wavelet-based filtering algorithm greatly
improves the stability to Poisson noise.
PMID- 11008963
TI - Dose efficiency and low-contrast detectability of an amorphous silicon x-ray
detector for digital radiography.
AB - The effect of dose reduction on low-contrast detectability is investigated
theoretically and experimentally for a production grade amorphous silicon (a-Si)
x-ray detector and compared with a standard thoracic screen-film combination. A
non-prewhitening matched filter observer model modified to include a spatial
response function and internal noise for the human visual system (HVS) is used to
calculate a signal-to-noise ratio (SNR) related to object detectability. Other
inputs to the SNR calculation are the detective quantum efficiency (DQE) and the
modulation transfer function (MTF) of the imaging system. Besides threshold
detectability, the model predicts the equivalent perception dose ratio (EPDR),
which is the fraction of the screen film exposure for which the digital detector
provides equal detectability. Images of a contrast-detail phantom are obtained
with the digital detector at dose levels corresponding to 27%, 41%, 63% and 100%
of the dose used for screen-film. The images are used in a four-alternative
forced choice (4-AFC) observer perception study in order to measure threshold
detectability. A statistically significant improvement in contrast detectability
is measured with the digital detector at 100% and 63% of the screen-film dose.
There is no statistical difference between screen-film and digital at 41% of the
dose. On average, the experimental EPDR is 44%, which agrees well with the model
prediction of 40%.
PMID- 11008964
TI - Dental radiography: tooth enamel EPR dose assessment from Rando phantom
measurements.
AB - Electron paramagnetic resonance dosimetry of tooth enamel is now established as a
suitable method for individual dose reconstruction following radiation accidents.
The accuracy of the method is limited by some confounding factors, among which is
the dose received due to medical x-ray irradiation. In the present paper the EPR
response of tooth enamel to endoral examination was experimentally evaluated
using an anthropomorphic phantom. The dose to enamel for a single exposure of a
typical dental examination performed with a new x-ray generation unit working at
65 kVp gave rise to a CO2- signal of intensity similar to that induced by a dose
of about 2 mGy of 60Co. EPR measurements were performed on the entire tooth with
no attempt to separate buccal and lingual components. Also the dose to enamel for
an orthopantomography exam was estimated. It was derived from TLD measurements as
equivalent to 0.2 mGy of 60Co. In view of application to risk assessment
analysis, in the present work the value for the ratio of the reference dose at
the phantom surface measured with TLD to the dose at the tooth measured with EPR
was determined.
PMID- 11008966
TI - A study of the directional response of ultraviolet radiometers: I. Practical
evaluation and implications for ultraviolet measurement standards.
AB - The directional responses of a range of ultraviolet radiometers commonly used for
irradiance measurements of UVB and UVC have been studied. Radiometers with 24
diffuser/filter combinations were assessed using a deuterium source, and three
different diffuser/filter designs were assessed using a monochromatic source. The
directional responses of the radiometers have been calculated and expressed in
terms of figures of merit similar to those described for (photopic) illuminance
meters in BS 667 and CIE 69. Those radiometers that performed best for the
measurement of both small and extended sources of UVB and UVC had raised PTFE
diffusers. We conclude that UV radiometers with a directional response error f2 <
10% are readily available commercially, and that it would be appropriate for
future ultraviolet standards to set an upper limit of 5% on f2. This would ensure
that the overall uncertainty in irradiance measurements of extended ultraviolet
sources is not dominated by the error in the directional response of the
radiometer.
PMID- 11008965
TI - An evaluation of near infrared spectroscopy and cryospectrophotometry estimates
of haemoglobin oxygen saturation in a rodent mammary tumour model.
AB - Haemoglobin oxygen saturation in subcutaneous rat mammary tumours was measured
using near infrared spectroscopy (NIRS) in vivo and in rapidly frozen sections
from the same tumours using cryospectrophotometry, which reports oxygen
saturation in individual blood vessels to depths of 4 mm from the tissue surface.
Measurements were performed on tumours while animals breathed either room air or
carbogen. In five of nine tumours, the average saturation calculated from
cryospectrophotometric measurements agreed with that determined from NIRS to
within 13%, and in four of these five tumours agreement was 5% or better. In the
remaining four of nine tumours, where agreement was poor, the volume-averaged
saturations estimated from NIRS were consistently higher than those calculated
from cryospectrophotometry. Monte Carlo simulations demonstrated that the depth
of tissue probed by NIRS was significantly greater than that sampled by
cryospectrophotometry. Analysis of the frequency of severely hypoxic vessels
showed that when NIRS reported a saturation of approximately 70% or higher, the
fraction of tumour vessels with saturations less than 10% was limited to 0.06 or
less. Sensitivity and specificity analysis suggests that NIRS and NIRS imaging
may identify clinically relevant hypoxia, even when its spatial extent is below
the resolution limit of the NIRS technique.
PMID- 11008967
TI - A study of the directional response of ultraviolet radiometers: II. Implications
for ultraviolet phototherapy derived from computer simulations.
AB - A theoretical model has been used to simulate irradiances for ultraviolet (UV)
phototherapy cabinets and other sources. The accuracy of the simulation results
has been checked by comparison with experimental measurements. The simulations
have been used to study the influence of different factors on UV phototherapy
exposure and to develop recommendations for the operation and calibration of
phototherapy cabinets. Many radiometers used in the evaluation of skin doses have
input optics with directional responses that are not proportional to the cosine
of the angle of incidence for the UV radiation. Data on radiometer directional
responses have been incorporated into the simulations, which show that the poor
directional responses for some radiometers currently in use will give errors of
20-50% in the assessment of irradiance. The influence of lamp source geometries
employed for radiometer calibration has been investigated. UV phototherapy
dosimetry commonly uses a spectroradiometer and a radiometer in the transfer of
irradiance calibrations from a small standard UV lamp to a large-area source with
a different UV spectrum. Recommendations are given on the range of acceptability
for radiometer directional responses and a method is described for determining
whether these are fulfilled. Recommendations are made on the techniques that
should be used for calibration.
PMID- 11008968
TI - Three-dimensional BANG gel dosimetry in conformal carbon ion radiotherapy.
AB - In this study we applied BANG polymer-gel dosimetry using magnetic resonance
imaging (MRI) to densely ionizing radiation such as carbon ion beams. BANG
polymer gels were irradiated with a quadratic field of monoenergetic 12C ions at
different beam energies in the range of 135 MeV u(-1) to 410 MeV u(-1). They were
irradiated at the radiotherapy facility of the GSI, Darmstadt, Germany. Our
object was to examine the saturation effect for densely ionizing radiation that
occurs at high values of linear energy transfer (LET). The examination yielded
the first effectiveness values that will be discussed in the following sections.
A solid sphere and a hollow sphere were both irradiated with a horizontal pencil
beam from the raster scanning facility at energies of 268 MeV u(-1) (solid
sphere) and 304 MeV u(-1) (hollow sphere) respectively. MR dosimetry measurements
were compared with data from a planning system. As far as quality is concerned,
there is good agreement between the measured dose distributions of both samples
and the dose maps from the planning software. The measured MR signals cannot be
converted into absolute dose, since the relative efficiency is still unknown for
mixed radiation fields of primary carbon ions and it is known only to a limited
extent for nuclear fragments with different energies from highly energetic photon
radiation. Model calculations are in progress in order to facilitate conversions
of measured MR signals into dose.
PMID- 11008969
TI - A novel tracking technique for the continuous precise measurement of tumour
positions in conformal radiotherapy.
AB - Changing tumour positions induced by organ motion can impede the full
exploitation of the strengths of conformal radiotherapy. The unnecessary
irradiation of healthy tissue surrounding the target volume can be the
consequence. To overcome this, one should measure tumour positions directly and
continuously with high resolution in space and time. We have developed a novel
tracking technique which will allow this. The method can also be used to survey
and monitor the patient positioning. The proper functioning of our method has
been technically demonstrated at PSI with the help of phantom irradiation with
protons. Implementation into the clinical environment is now beginning.
PMID- 11008970
TI - Influence of sulphuric acid contaminants on Fricke dosimetry.
AB - The sulphuric acid used for the preparation of the Fricke dosimeter solution may
contain trace impurities that can affect the yield of ferric ions. Two methods,
pre-irradiation or oxidation with hydrogen peroxide, have been proposed to reduce
the influence of these impurities. Fricke users sometimes omit this treatment. In
the present work Fricke solutions prepared from six different brands and
qualities of sulphuric acid were compared in order to study any influences of the
acid on the ferric ion yield. It was shown that the use of analytical grade
sulphuric acid from one manufacturer resulted in a reduction of the ferric ion
yield of about 5% at an absorbed dose of approximately 20 Gy. If this solution
were to be used for an absolute dose determination together with epsilon(m) G
values from the literature the absorbed dose would be underestimated by the same
amount.
PMID- 11008971
TI - Hypoproteinemia predicts acute respiratory distress syndrome development, weight
gain, and death in patients with sepsis. Ibuprofen in Sepsis Study Group.
AB - OBJECTIVE: Starling's equation indicates that reduced oncotic pressure gradients
will favor edema formation, and the current consensus definition of acute
respiratory distress syndrome (ARDS) excludes only the hydrostatic pressure
contribution. We hypothesized that low serum total protein levels might correlate
with the likelihood of ARDS in at-risk patients because serum total protein is
the chief determinant of oncotic pressure in humans. DESIGN: Regression analysis
to compare outcomes in patients with low serum total protein levels with outcomes
in patients with normal serum total protein levels with respect to weight change,
development of ARDS, and mortality. SETTING: Intensive care units (ICUs) of seven
clinical centers in North America. PATIENTS: A total of 455 ICU patients who met
consensus criteria for severe sepsis (178 of whom developed ARDS) from a recently
completed prospective clinical trial. INTERVENTION: None. MEASUREMENTS AND MAIN
RESULTS: We found that 92% of the patients developing ARDS had low or borderline
serum total protein levels (<6 g/dL). Logistic and multiple regression analyses
confirmed that of 18 clinical variables, initial serum total protein level and
protein change over time were the most statistically significant predictors of
weight gain, prolonged mechanical ventilation, ARDS development, and mortality in
the study population. This correlation remained significant after adjustment for
the other major predictors of outcome present at baseline (ie, Acute Physiology
and Chronic Health Evaluation II score). CONCLUSIONS: Hypoproteinemia is
significantly correlated with fluid retention and weight gain, development of
ARDS and poor respiratory outcome, and mortality in patients with sepsis.
Prospective, randomized trials of serum protein manipulation are needed to
establish whether there is a cause-effect relationship to this association.
PMID- 11008972
TI - A new approach to Advance Directives.
AB - OBJECTIVE: To martial arguments for listing simplified Advance Directives on the
Medicare card. DESIGN AND MAIN RESULTS: Literature review shows that 90% of
patients do not have advance directives, that patients and doctors are both
remiss in discussing end-of-life issues, and that Medicare, insurance companies,
and hospitals do little to remedy this lapse. CONCLUSION: A case is made for
listing simplified Advance Directives on the Medicare card.
PMID- 11008973
TI - Phase I trial of the recombinant soluble complement receptor 1 in acute lung
injury and acute respiratory distress syndrome.
AB - OBJECTIVE: To determine the safety, pharmacokinetics, biological effects, and
immunogenicity of recombinant soluble complement receptor 1 (TP10) in patients
with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).
DESIGN: Open label, ascending dosage, phase I trial. SETTING: Two academic
teaching hospitals. PATIENTS: A total of 24 patients diagnosed with ALI/ARDS.
INTERVENTION: A single, 30-min intravenous infusion of 0.1, 0.3, 1, 3, or 10
mg/kg TP10. MEASUREMENTS AND MAIN RESULTS: Serum levels of TP10 increased in
proportion to the dose. Mean variable estimates (+/-SD) were half-life of
disposition 69.7 +/- 39.7 hrs, plasma clearance 2.39 +/- 1.32 mL/hr/kg, and
volume of distribution 190.6 +/- 135.0 mL/kg. Inhibition of complement activity,
measured by CH50, was significant for the interaction of dose and time (p =
.024). The C3a levels demonstrated a trend for dose which did not reach
statistical significance (p = .090) and soluble C5b-9 levels were significant
only for dose (p = .023). As expected by the proposed physiologic mechanism, C4a
levels were not affected by TP10, dose, or time. The overall mortality rate was
33%. Neither the type nor the frequency rate of specific adverse events were
substantially different between dose groups. Seven adverse events in four
patients were thought to be possibly related to TP10. CONCLUSIONS: TP10 has a
half-life of approximately 70 hrs and at doses > or =1 mg/kg, significantly
inhibits complement activity at the levels of C3 and C5 in patients with
ALI/ARDS. Complement inhibition was more prolonged over time with TP10 doses of 3
and 10 mg/kg. TP10 appears to be safe at the doses tested. Further studies will
be required to completely assess the impact of TP10 on pathophysiology and
clinical outcome in patients with ALI/ARDS.
PMID- 11008974
TI - Impact of colony-stimulating factor therapy on clinical outcome and frequency
rate of nosocomial infections in intensive care unit neutropenic patients.
AB - OBJECTIVES: To determine whether the use of recombinant human granulocyte colony
stimulating factor (G-CSF, filgrastim) reduces the mortality rate and the
frequency rate of nosocomial infections in neutropenic patients requiring
intensive care unit (ICU) admission. DESIGN: Retrospective consecutive case
series analysis. SETTING: Medical ICU of a teaching hospital. PATIENTS: We
compared two groups of patients, according to whether or not they received G-CSF.
In the ICU, 28 leukopenic patients received filgrastim (5 microg of body weight
per day intravenously). In all these patients, G-CSF was continued until recovery
from leukopenia, defined as a leukocyte count >1,000/mm3. A total of 33 ICU
leukopenic patients did not receive G-CSF. End points included leukocyte count,
bone marrow recovery, frequency of ICU nosocomial infections (pneumonia, urinary
tract, and catheter-related infections), and mortality rate. MEASUREMENTS AND
MAIN RESULTS: There were no differences in number of patients who recovered from
leukopenia or in whom blood leukocyte count increased. Nosocomial infections
occurred in the same percentage in both groups. The percentage of patients who
died was identical in both groups. The percentage of patients with and without
filgrastim therapy who recovered from leukopenia but died, was 86% and 78%,
respectively. CONCLUSION: In the ICU, clinical outcome of neutropenic patients
was not changed by G-CSF therapy. It is possible that G-CSF therapy may not be
helpful in improving the ICU clinical outcome of neutropenic patients. Additional
controlled studies designed to address this question are warranted.
PMID- 11008975
TI - Pulmonary endothelial permeability and circulating neutrophil-endothelial markers
in patients undergoing esophagogastrectomy.
AB - OBJECTIVE: Esophagogastrectomy is an established surgical treatment for
esophageal malignancy. The postoperative period may be complicated by the
development of acute lung injury syndromes and thus, may provide a useful model
in which to study the early pathogenic mechanisms of inflammatory lung injury.
DESIGN: Open, prospective study. SETTING: High dependency and intensive therapy
units. PATIENTS: Eight healthy male volunteers and 20 patients in the early
postoperative period INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The lung
protein accumulation index (PAI) of radiolabeled transferrin was determined by
using a portable, double-isotope system. The following circulating inflammatory
markers-thought to reflect neutrophil-endothelial activation and injury including
circulating neutrophil elastase-soluble L-, E-, and P-selectins and
thrombomodulin and von Willebrand factor antigen were assayed from venous blood
samples The PAI for healthy volunteers was median -0.5 (range, -1.73 to 0.27) x
10(-3)/min and for patients undergoing esophagogastrectomy -0.005 (range, -1.53
to 2.28) x 10(-3)/min. There was no statistical difference between the two
groups. In the postesophagogastrectomy group, a significant elevation in
circulating levels of neutrophil elastase, soluble P- and E-selectin,
thrombomodulin, and von Willebrand factor antigen were observed relative to the
control group but only circulating plasma elastase demonstrated a significant
correlation with the PAI (r2 = .23, p =.03). CONCLUSIONS: The data suggest
patients undergoing esophagogastrectomy develop a inflammatory response but this
is not a surrogate of permeability and other factors are likely to determine
persistent injury to the alveolar-capillary barrier function in this patient
group.
PMID- 11008976
TI - Role of interleukin-10 on hyporesponsiveness of endotoxin during surgery.
AB - OBJECTIVE: To examine whether surgical stress causes blood cells to lose their
responsiveness to endotoxin during surgery. DESIGN: Prospective case series.
SETTING: A university hospital. PATIENTS: Sixteen volunteers classified as
American Society of Anesthesiologists physical status I-II who were scheduled for
elective distal partial gastrectomy. INTERVENTIONS: We studied nine patients who
underwent elective distal partial gastrectomy. Blood samples for tumor necrosis
factor (TNF) and interleukin (IL)-10 assay were obtained before anesthesia,
preincision, 2 hrs and 4 hrs postincision, postextubation, and 24 hrs
postincision. The rest of each blood sample was diluted with 5 volumes of
endotoxin-free saline, incubated for 4 hrs in the presence of lipopolysaccharide
(LPS), centrifuged to remove cells, and assayed for TNF. In another seven
patients, antihuman IL-10 antibody was added into the diluted whole blood sample
before LPS stimulation. MEASUREMENTS AND MAIN RESULTS: TNF activity was not
detected in the blood of any patient throughout the study. In contrast, plasma
cortisol and IL-10 levels increased rapidly during surgery (p < .01, p < .05,
respectively). LPS-induced TNF activity in whole blood decreased significantly
during surgery (p < .01) and recovered to control levels by 24 hrs postincision.
The peak suppression of LPS-induced TNF and the peak value of plasma IL-10 levels
occurred postextubation. Treatment with anti-IL-10 antibody partially restored
the ability of LPS to induce TNF activity postextubation (p < .05). CONCLUSIONS:
Surgical trauma rapidly induces a transient hyporesponsiveness of blood cells to
endotoxin. Plasma IL-10, which increases during surgery, participates in this
hyporesponsiveness.
PMID- 11008977
TI - Usefulness of procalcitonin for diagnosis of infection in cardiac surgical
patients.
AB - OBJECTIVE: To determine the value of procalcitonin (PCT) as a marker of
postoperative infection after cardiac surgery. DESIGN: A prospective single
institution three phase study. SETTING: University cardiac surgical intensive
care unit (31 beds). PATIENTS: Phase 1: To determine the normal perioperative
kinetics of PCT, 20 consecutive patients undergoing elective cardiac surgery with
cardiopulmonary bypass were included. Phase 2: To determine whether PCT may be
useful for diagnosis of postoperative infection, 97 consecutive patients with
suspected infection were included. Phase 3: To determine the ability of PCT to
differentiate patients with septic shock from those with cardiogenic shock, 26
patients with postoperative circulatory failure were compared. MEASUREMENTS AND
MAIN RESULTS: Phase 1: Serum samples were drawn for PCT determination after
induction of anesthesia (baseline), at the end of surgery, and daily until
postoperative day (POD) 8. Baseline serum PCT concentration was 0.17 +/- 0.08
ng/mL (mean +/- SD). Serum PCT increased after cardiac surgery with a peak on POD
1 (1.08 +/- 1.36). Serum PCT returned to normal range on POD 3 and remained
stable thereafter. Phase 2: In patients with suspected infection, serum PCT was
measured at the same time of C-reactive protein (CRP) and bacteriologic samples.
Among the 97 included patients, 54 were infected with pneumonia (n = 17),
bacteremia (n = 16), mediastinitis (n = 9), or septic shock (n = 12). In the 43
remaining patients, infection was excluded by microbiological examinations. In
noninfected patients, serum PCT concentration was 0.41 +/- 0.36 ng/mL (range,
0.08-1.67 ng/mL). Serum PCT concentration was markedly higher in patients with
septic shock (96.98 +/- 119.61 ng/mL). Moderate increase in serum PCT
concentration occurred during pneumonia (4.85 +/-3.31 ng/mL) and bacteremia (3.57
+/- 2.98 ng/mL). Serum PCT concentration remained low during mediastinitis (0.80
+/- 0.58 ng/mL). Five patients with mediastinitis, two patients with bacteremia,
and one patient with pneumonia had serum PCT concentrations of <1 ng/mL. These
eight patients were administered antibiotics previously and serum PCT was
measured during a therapeutic antibiotic window. For prediction of infection by
PCT, the best cutoff value was 1 ng/mL, with sensitivity 85%, specificity 95%,
positive predictive value 96%, and negative predictive value 84%. Serum CRP was
high in all patients without intergroup difference. For prediction of infection
by CRP, a value of 50 mg/L was sensitive (84%) but poorly specific (40%).
Comparing the area under the receiver operating characteristic curves, PCT was
better than CRP for diagnosis of postoperative sepsis (0.82 for PCT vs. 0.68 for
CRP). Phase 3: Serum PCT concentration was significantly higher in patients with
septic shock than in those with cardiogenic shock (96.98 +/- 119.61 ng/mL vs.
11.30 +/- 12.3 ng/mL). For discrimination between septic and cardiogenic shock,
the best cutoff value was 10 ng/mL, with sensitivity of 100% and specificity of
62%. CONCLUSION: Cardiac surgery with cardiopulmonary bypass influences serum PCT
concentration with a peak on POD 1. In the presence of fever, PCT is a reliable
marker for diagnosis of infection after cardiac surgery, except in patients who
previously received antibiotics. PCT was more relevant than CRP for diagnosis of
postoperative infection. During a postoperative circulatory failure, a serum PCT
concentration >10 ng/mL is highly indicative of a septic shock.
PMID- 11008978
TI - Randomized trial of the use of heliox as a driving gas for updraft nebulization
of bronchodilators in the emergent treatment of acute exacerbations of chronic
obstructive pulmonary disease.
AB - OBJECTIVE: To determine whether the bronchodilator effects of albuterol and
ipratropium bromide are greater if updraft nebulization is driven by 80% helium
and 20% oxygen (HELIOX) than if driven by compressed room air (AIR) during the
treatment of an acute exacerbations of chronic obstructive pulmonary disease
(COPD). SETTING: The emergency department of a 750-bed inner-city community
hospital. METHODS: Over a 12-month period, a convenience sample of 50 normoxic
patients presenting with signs and symptoms of an acute exacerbation of COPD were
prospectively randomized to receive either HELIOX or AIR as the driving gas for
updraft nebulization of a mixture of albuterol 2.5 mg and ipratropium bromide 0.5
mg. Additional aerosol treatments with albuterol 2.5 mg were given at 20, 40, and
120 mins after randomization using the assigned gas. Spirometry was obtained
while breathing room air before the first treatment (baseline) and at 1 hr and 2
hrs after the initiation of treatment. The primary measure of efficacy was the
change in percent of predicted forced expiratory volume in 1 sec (FEV1) over the
treatment period. A secondary measure of efficacy was the change in percentage of
predicted forced expiratory flow after 25% to 75% of vital capacity had been
expelled (FEF25-75). RESULTS: Twenty-five patients were randomized to each
treatment group. Three patients (1 HELIOX, 2 AIR) were unable to complete the
study. The baseline FEV1was 44% (95% confidence interval, 35% to 52%) of
predicted in the HELIOX group and 39 (31% to 46%) of predicted in the AIR group.
There were no adverse outcomes observed in either the HELIOX group or the AIR
group. There were no significant differences in the change of FEV1 between the
two groups by either the 1 hr or 2 hr time point (1 hr, HELIOX + 10% [7% to 13%],
AIR + 9% [5% to 13%]; 2 hr HELIOX + 10% [6% to 15%], AIR + 10% [6% to 14%]). The
improvement in FEF25-75 was significantly greater in the HELIOX group than in the
AIR group at both the 1 hr time point (HELIOX + 14% [7% to 22%] vs. AIR + 7% [3%
to 10%], p = .05) and at the 2 hr time point (HELIOX + 15% [8% to 21%] vs. AIR +
7% [4% to 11%], p = .05). CONCLUSION: Use of HELIOX as a driving gas for the
updraft nebulization of bronchodilators during the first 2 hrs of treatment of an
acute COPD exacerbation failed to improve FEV1 faster than the use of AIR. The
faster improvement in FEF25-75 during the first 2 hrs of treatment was small and
of uncertain clinical significance.
PMID- 11008979
TI - Venous blood flow measurement by determination of change in venous hemoglobin
saturation.
AB - OBJECTIVE: To evaluate a method of measuring venous blood flow in vitro by using
the Fick principle and change in saturation of venous blood and to apply the
method to the clinical measurement of hepatic blood flow. DESIGN: Experimental
study using an in vitro model and clinical study for critically ill patients.
SETTING: Department of Anesthesiology and Intensive Care Medicine in Osaka City
University Medical School. MODEL: Human blood deoxygenated by bubbling of
nitrogen was circulated in a closed circuit at 10-120 mL/min by a roller pump. A
fiber optic sensor was attached to the circuit for continuous monitoring of
hemoglobin saturation. PATIENTS: Eight critically ill patients, aged 54.3 +/-
15.1 yrs, were studied. INTERVENTIONS: Hemoglobin saturation was changed in the
in vitro study by the injection of 0.2 mL of oxygenated blood. Signals from the
optical fiber were analogue-digital converted and recorded in a computer. In the
clinical study, an oximetry catheter was inserted into the inferior vena cava
(IVC) via the femoral vein. Arterial blood (10 mL) was drawn from the radial
artery, and injected into the IVC. The changes in oxygen saturation in the venous
blood were recorded. MEASUREMENTS AND MAIN RESULTS: Blood flow was calculated
using the Fick principle, assuming that all the injected blood passes through the
sensor. In vitro estimation of blood flow was well correlated with the actual
flow (r2 = .94). IVC blood flow was measured above and below the merging point of
the hepatic vein. The difference of the two values was assumed to represent
hepatic blood flow. IVC blood flow was calculated by the same method as for the
in vitro study. The blood flows in the IVC above and below the anastomosis with
the hepatic vein were 2.82 +/-0.56 (SD) Umin and 1.96 +/- 0.61 (SD) L/min.
Average estimated hepatic blood flow was 0.86 L/min (range, 0.34-1.75 Umin).
CONCLUSION: We examined the accuracy and reliability of this new method in the
present in vitro study. This method may be clinically useful for measuring
hepatic blood flow.
PMID- 11008980
TI - Noninvasive continuous positive airway pressure in neutropenic patients with
acute respiratory failure requiring intensive care unit admission.
AB - OBJECTIVE: To evaluate the tolerance and the efficacy of noninvasive continuous
positive airway pressure (CPAP) in severe acute respiratory failure occurring in
intensive care unit (ICU) neutropenic patients with hematologic malignancies, and
to establish predictive variables of efficacy of this method. DESIGN: Prospective
study over a 5-yr period. SETTING: Hematologic and medical intensive care unit of
a teaching hospital. METHODS: Among 129 neutropenic patients admitted to the ICU,
64 patients presented with febrile acute hypoxemic normocapnic respiratory
failure (PaO2/FIO2 ratio <200) and were enrolled. In addition to standard
therapy, patients received CPAP with a facial mask. The initial settings of the
CPAP were 6 cm H2O positive end-expiratory pressure and FIO2 0.8 (80%).
Physiologic measurements were performed at the end of 45 mins of ventilation with
first adjustments. CPAP was used with a sequential mode (45 mins/3 hrs). CPAP was
efficient if intubation was avoided. RESULTS: The setting of CPAP, after
adjustments, was as follows: positive end-expiratory pressure 7 +/- 1 cm H2O and
FIO2 0.7 +/- 0.1 (70% +/- 10%). For the 64 patients, CPAP was administered for a
total of 6 +/- 2 hrs during the first 24 hrs. The mean duration of CPAP was 7 +/-
3 days. A reduction in respiratory rate to less than 25 breaths/min was achieved
in 53% of patients. PaO2/FIO2 ratio increased from 128 +/- 32 to 218 +/- 28. CPAP
was successful in avoiding endotracheal intubation in 16/64 patients. A total of
16 responders and four nonresponders survived. Hepatic failure was a criterion
indicating the failure of CPAP: 1/16 vs. 26/48 (p = .001). In multivariate
analysis, two variables were predictive of failure of CPAP: Simplified Acute
Physiology Score II (58 +/- 14 vs. 41 +/- 11) and a hepatic failure at the entry
into the study. CONCLUSION: CPAP was efficient in 25% of cases. All the
responders survived. This noninvasive method was used as a way to avoid
mechanical ventilation, which is well correlated with a poor prognosis in
neutropenic ICU patients. Further controlled studies are needed to confirm the
efficacy of noninvasive CPAP and to evaluate the most appropriate selection of
immunocompromised patients.
PMID- 11008981
TI - The relationship between visceral ischemia, proinflammatory cytokines, and organ
injury in patients undergoing thoracoabdominal aortic aneurysm repair.
AB - OBJECTIVES: Plasma proinflammatory, anti-inflammatory cytokine, and soluble tumor
necrosis factor (TNF) receptor concentrations were examined in hospitalized
patients after abdominal and thoracoabdominal aortic aneurysm (TAAA) repair, with
and without left atrial femoral bypass. Changes in plasma cytokine concentrations
were related to the duration of visceral ischemia and the frequency rate of
postoperative, single, or multiple system organ dysfunction (MSOD). DESIGN:
Prospective, observational study. SETTING: Two academic referral centers in the
United States and The Netherlands. PATIENTS: We included 16 patients undergoing
TAAA repair without left atrial femoral bypass, 12 patients undergoing TAAA
repair with left atrial femoral bypass, and nine patients undergoing infrarenal
aortic aneurysm repair. MEASUREMENTS AND MAIN RESULTS: Timed, arterial blood
sampling for proinflammatory and anti-inflammatory cytokine and soluble TNF
receptor concentrations (p55 and p75), and prospective assessment of
postoperative single and MSOD. Plasma appearance of TNF-alpha, interleukin (IL)
6, IL-8, and IL-10 peaked 1 to 4 hrs after TAAA repair, and concentrations were
significantly elevated compared with infrarenal abdominal aortic aneurysm repair
(p < .05). Left atrial femoral bypass significantly reduced the duration of
visceral ischemia (p < .05) and the systemic TNF-alpha, p75, and IL-10 responses
(p < .05). Plasma TNF-alpha concentrations >150 pg/mL were more common in
patients with extended visceral ischemia times (>40 mins). Additionally, patients
with early peak TNF-alpha concentrations >150 pg/mL and IL-6 levels >1,000 pg/mL
developed MSOD more frequently than patients without these elevated plasma
cytokine levels (both p < .05). CONCLUSIONS: Thoracoabdominal aortic aneurysm
repair results in the increased plasma appearance of TNF-alpha, IL-6, IL-8, IL
10, and shed TNF receptors. The frequency and magnitude of postoperative organ
dysfunction after TAAA repair is associated with an increased concentration of
the cytokines, TNF-alpha, and IL-6 and the increased plasma levels of these
cytokines appear to require extended visceral ischemia times.
PMID- 11008982
TI - High adenosine plasma concentration as a prognostic index for outcome in patients
with septic shock.
AB - OBJECTIVE: Sepsis and septic shock are a common cause of mortality in critically
ill patients. Many substances have been implicated in the pathophysiology of
these syndromes. We postulated that adenosine may be implicated in the sepsis- or
septic shock-induced blood pressure failure. Indeed, this nucleoside is a strong
endogenous vasodilating agent released by endothelial cells and myocytes under
circumstances of metabolic stress, such as during critical illness. DESIGN: A
prospective, comparative observational study. SETTING: The adult intensive care
unit of a tertiary care university hospital. PATIENTS: We measured adenosine
plasma concentration (APC) in patients with severe sepsis (n = 11), in patients
with septic shock (n = 14), in patients with hemorrhagic traumatic shock (n =
14), and in 12 healthy volunteers. APC was evaluated every 12 hrs over 3 days.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At study entry, we found that
APC was higher in patients with septic shock (mean +/- so = 8.4 +/-3.5
micromol/L) than in patients with hemorrhagic traumatic shock (1.1 +/- 0.6
micromol/L) and controls (0.8 +/- 0.3 micromol/L). Intermediate values (3.9 +/-
1.9 micromol/L) were found in patients with severe sepsis. APC in patients with
traumatic shock did not differ from controls. In the course of the
hospitalization, for both sepsis and septic shock patients, APC decreased
significantly but remained higher than controls 72 hrs after entry into the
study. In the septic shock group, APC was significantly higher in the nonsurvivor
group (n = 6) than in the survivor group (n = 8), whatever the time of sample
collection and assay. CONCLUSIONS: High adenosine plasma concentrations are found
in patients with septic shock but not during traumatic shock, or in healthy
volunteers. Intermediate values of circulating adenosine are found in patients
with severe sepsis. APC may be a prognostic index for outcome in septic patients,
with much higher values being found in nonsurvivors.
PMID- 11008983
TI - G-protein beta3 subunit gene (GNB3) polymorphism 825C-->T in patients with
hypertensive crisis.
AB - OBJECTIVE: The polymorphism 825C-->T in exon 10 of the gene GNB3 encoding the
beta3 subunit of heterotrimeric guanine nucleotide binding regulatory proteins (G
proteins) results in a splicing variant (GNB3-s) in which the nucleotides 498-620
of exon 9 are deleted. The T allele has been shown to be overrepresented in
patients with essential hypertension. Because GNB3-s may support the development
of severe elevation of blood pressure, we hypothesized that GNB3 825C-->T may be
present more frequently in patients with hypertensive crisis. DESIGN: Case
control study. SETTING: Department of Emergency Medicine at the University
Hospital of Vienna, Vienna, Austria. PATIENTS: A total of 174 patients admitted
to an emergency department for treatment of hypertensive crisis diagnosed as
suffering from essential hypertension. INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: Patients were genotyped for the 825C-->T transition in GNB3. An equal
number of age- and gender-matched normotensive, healthy individuals served as the
control population. The allele frequency of 825C-->T in the GNB3 gene was 0.310
in patients with hypertensive crisis and 0.342 in the control group. There was no
difference in genotype distribution and allele frequency between the patients and
the age- and gender-matched control group or between the observed prevalence and
the occurrence rate expected from the Hardy-Weinberg principle within each group.
CONCLUSIONS: GNB3 825C-->T is not associated with the phenotype of hypertensive
crisis in patients suffering from essential hypertension. Furthermore, our data
do not support the concept that the 825C-->T transition in the GNB3 gene is
associated with essential hypertension.
PMID- 11008984
TI - Rapid onset of intestinal epithelial and lymphocyte apoptotic cell death in
patients with trauma and shock.
AB - OBJECTIVE: Apoptosis is a cellular suicide program that can be activated by cell
injury or stress. Although a number of laboratory studies have shown that
ischemia/reperfusion injury can induce apoptosis, few clinical studies have been
performed. The purpose of this study was to determine whether apoptosis is a
major mechanism of cell death in intestinal epithelial cells and lymphocytes in
patients who sustained trauma, shock, and ischemia/ reperfusion injury. DESIGN:
Intestinal tissues were obtained intraoperatively from 10 patients with acute
traumatic injuries as a result of motor vehicle collisions or gun shot wounds. A
control population consisted of six patients who underwent elective bowel
resections. Apoptosis was evaluated by conventional light microscopy, laser
scanning confocal microscopy using the nuclear staining dye Hoechst 33342,
immunohistochemical staining for active caspase-3, and immunohistochemical
staining for cytokeratin 18. SETTING: Academic medical center. PATIENTS: Patients
with trauma or elective bowel resections. MEASUREMENTS AND MAIN RESULTS:
Extensive focal crypt epithelial and lymphocyte apoptosis were demonstrated by
multiple methods of examination in the majority of trauma patients. Trauma
patients having the highest injury severity score tended to have the most severe
apoptosis. Repeat intestinal samples obtained from two of the trauma patients who
had a high degree of apoptosis on initial evaluation were negative for apoptosis
at the time of the second operation. Tissue lymphocyte apoptosis was associated
with a markedly decreased circulating lymphocyte count in 9 of 10 trauma
patients. CONCLUSIONS: Focal apoptosis of intestinal epithelial and lymphoid
tissues occurs extremely rapidly after injury. Apoptotic loss of intestinal
epithelial cells may compromise bowel wall integrity and be a mechanism for
bacterial or endotoxin translocation into the systemic circulation. Apoptosis of
lymphocytes may impair immunologic defenses and predispose to infection.
PMID- 11008985
TI - No long-term benefit from hypothermia after severe traumatic brain injury with
secondary insult in rats.
AB - OBJECTIVES: To evaluate the effect of application of transient, moderate
hypothermia on outcome after experimental traumatic brain injury (TBI) with a
secondary hypoxemic insult. DESIGN: Prospective, randomized study. SETTING:
University-based animal research facility. SUBJECTS: Male Sprague-Dawley rats.
INTERVENTIONS: All rats were subjected to severe TBI followed by 30 mins of
moderate hypoxemia, associated with mild hypotension. Rats were randomized to
three groups: a) normothermia (37 degrees C + 0.5 degrees C); b) immediate
hypothermia (32 degrees C +/- 0.5 degrees C initiated after trauma, before
hypoxemia); and c) delayed hypothermia (32 degrees C +/- 0.5 degrees C after
hypoxemia). The brain temperature was controlled for 4 hrs after TBI and
hypoxemia. MEASUREMENTS AND MAIN RESULTS: Animals were evaluated after TBI for
motor and cognitive performance using beam balance (days 1-5 after TBI), beam
walking (days 1-5 after TBI), and Morris Water Maze (days 14-18 after TBI)
assessments. On day 21 after TBI, rats were perfused with paraformaldehyde and
brains were histologically evaluated for lesion volume and hippocampal neuron
counts. All three groups showed marked deficits in beam balance, beam walking,
and Morris Water Maze performance. However, these deficits did not differ between
groups. There was no difference in lesion volume between groups. All animals had
significant hippocampal neuronal loss on the side ipsilateral to injury, but this
loss was similar between groups. CONCLUSIONS: In this rat model of severe TBI
with secondary insult, moderate hypothermia for 4 hrs posttrauma failed to
improve motor function, cognitive function, lesion volume or hippocampal neuronal
survival. Combination therapies may be necessary in this difficult setting.
PMID- 11008986
TI - C1 inhibitor prevents capillary leakage after thermal trauma.
AB - OBJECTIVE: In burned patients, activation of the complement and clotting systems
is suggested to play an important role in the development of the capillary leak
syndrome and inflammatory tissue destruction. In an animal model of thermal
trauma, the possible protective effect of C1 inhibitor (C1Inh), a major control
protein of both the complement and clotting systems, was investigated. DESIGN:
Prospective, controlled study. SETTING: Animal model. SUBJECTS: Healthy pigs
weighing 30 kg. INTERVENTIONS: Pigs were scalded for 25 secs with 75 degrees C
hot water to achieve a 30% total body surface deep partial-thickness burn. The
treatment group (n = 8) received C1Inh concentrate at an initial dose of 100
units/kg body weight immediately after thermal trauma, followed by three further
applications every 12 hrs. Two control groups included animals that were either
scalded (n = 8) or not scalded (n = 7) and treated with lactated Ringer's
solution. MEASUREMENTS: Before and at various time points after trauma blood
samples were analyzed for complement activation (APH50, CH50, SC5b-9, C3).
Continuous monitoring of hemodynamic variables was performed and postmortem
histologic examination of specimens from lung, heart, liver, kidney, stomach,
duodenum, jejunum, ileum, and colon was carried out. Aseptically collected
mesenteric lymph nodes were pooled and screened for bacterial translocation. For
evaluation of the burn wound, biopsies from defined scalded and not scalded areas
were taken daily. As a measure for edema formation, the weight of the animals was
recorded every 2 hrs. RESULTS: After C1Inh treatment, which led to a
significantly reduced complement activation, the clinical outcome was clearly
improved, as indicated by vital signs and as demonstrated by reduced edema
formation. Treated animals presented a diminished bacterial translocation.
Pathologic alterations were clearly diminished in the burned skin, in shock
related organs, and in the intestines. CONCLUSION: Application of C1Inh appears
to be an effective means to prevent capillary leakage and inflammatory tissue
destruction after thermal trauma.
PMID- 11008987
TI - Dynamic study of the distribution of microcirculatory blood flow in multiple
splanchnic organs in septic shock.
AB - OBJECTIVES: To study dynamic distribution of microcirculatory blood flow in
multiple splanchnic organs during septic shock; to test the hypothesis that
changes in microcirculatory blood flow in splanchnic organs correlate with
changes in regional flow during septic shock. DESIGN: A prospective, controlled,
animal study. SETTING: Animal laboratory in a university medical center.
SUBJECTS: Nine anesthetized and mechanically ventilated domestic pigs.
INTERVENTIONS: Systemic flow (cardiac output) was measured with thermodilution
and regional (superior mesenteric artery) flow with transit time flowmetry. Local
blood flow (microcirculatory flow) was continuously measured in splanchnic organs
(gastric, jejunal, and colon mucosa, liver, and pancreas) and the kidney with
multichannel laser Doppler flowmetry. Septic shock was induced with fecal
peritonitis. After 240 mins of sepsis, intravenous fluids were administered to
alter hypodynamic shock to hyperdynamic septic shock. MEASUREMENTS AND MAIN
RESULTS: In this severe septic shock model, systemic and regional flows decreased
by approximately 50% during the first 240 mins. Similar reductions were recorded
in microcirculatory flow in the mucosa of the stomach (-41%; p < .001) and colon
(-47%; p < .001). In the jejunal mucosa, on the other hand, flow remained
virtually unchanged. Microcirculatory flow was also significantly decreased in
the liver (-49%; p < .001), pancreas (-56%; p < .001), and kidney (-44%; p <
.001). Administration of intravenous fluids at 240 mins was followed by three
fold increases in systemic and regional flows (approximately 70% above baseline).
In the jejunal mucosa, flow also increased significantly above baseline (42%; p <
.001), whereas in the stomach and the colon, it barely reached baseline. Kidney
blood flow increased to baseline, whereas pancreas and liver flows remained 26%
(p < .05) and 34% (p < .001), respectively, below baseline. CONCLUSION: Changes
in microcirculatory blood flow in the splanchnic organs are heterogeneous, both
in early hypodynamic and in hyperdynamic septic shock, and cannot be predicted
from changes in systemic or regional flows. Microcirculatory blood flow in the
jejunal mucosa remains constant during early septic shock, whereas pancreatic
blood flow decreases significantly more than regional flow.
PMID- 11008988
TI - L-arginine attenuates trauma-hemorrhage-induced liver injury.
AB - OBJECTIVES: Liver injury is common after trauma-hemorrhage for which the
underlying mechanism is not clear. Although administration of the essential amino
acid L-arginine has been reported to restore the depressed cardiovascular
functions and cell-mediated immune responses after trauma-hemorrhage, it remains
unknown whether L-arginine protects against liver injury under those conditions.
DESIGN: A prospective, controlled animal study. SETTING: A university research
laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats underwent
sham operation or laparotomy and were bled to and maintained at a mean arterial
blood pressure of 40 mm Hg until 40% of the maximum shed blood volume was
returned in the form of lactated Ringer's solution. Hemorrhaged rats were then
resuscitated with lactated Ringer's solution, four times the maximum shed blood
volume over 1 hr. During resuscitation, animals received either 300 mg/kg of L
arginine or saline (vehicle) intravenously. At 3 and 5 hrs after resuscitation,
rats were killed, blood was obtained, and the liver was fixed for histology
(hematoxylin & eosin staining). Plasma glutathione S-transferase (a marker of
liver damage), L-arginine, citrulline, and ornithine concentrations were
assessed. MEASUREMENTS AND MAIN RESULTS: The increased concentrations of plasma
glutathione S-transferase observed in vehicle-treated hemorrhage animals were
normalized with L-arginine treatment at 5 hrs after resuscitation. Moreover, the
histology indicated that L-arginine prevented liver edema and neutrophil
infiltration after trauma-hemorrhage. Plasma L-arginine and citrulline were
increased in L-arginine-treated rats. CONCLUSIONS: Because citrulline is a by
product of nitric oxide generation by nitric oxide synthase from L-arginine, this
amino acid may be a useful adjunct for preventing hepatic injury after trauma
hemorrhage via endothelial derived nitric oxide production.
PMID- 11008989
TI - Nuclear factor-kappaB activation in mouse lung lavage cells in response to
Streptococcus pneumoniae pulmonary infection.
AB - OBJECTIVES: To assess the state and activation kinetics of the nuclear
transcription regulatory protein nuclear factor-kappB (NF-kappaB) in lung lavage
cells in a murine pneumococcal pneumonia model and to determine how the virulence
of the infecting organisms altered the activation state of NF-kappaB. DESIGN:
Experimental, comparative study of three Streptococcus pneumoniae strains that
induced three distinct pulmonary diseases. SETTING: Experimental laboratory in a
university-based medical center. SUBJECTS: Female BALB/cby mice, 8-10 wks of age.
INTERVENTIONS: We randomly divided the mice into the following five groups: a)
the control group; b) animals infected by virulent encapsulated S. pneumoniae
P4241 strain; c) animals infected by avirulent encapsulated S. pneumoniae P15986
strain; d) animals infected by avirulent unencapsulated S. pneumoniae R6 strain;
e) animals infected by virulent lysed S. pneumoniae P4241 strain. Animals were
anesthetized and infected by intratracheal delivery of 4 x 10(5) colony-forming
units (CFU) of S. pneumoniae per mouse or bacterial components equivalent to 4 x
10(5) CFU for lysed S. pneumoniae challenge. After intratracheal challenge with
virulent encapsulated strain P4241, mice developed acute pneumonia, became
bacteremic, and died within 3 to 5 days. None of the mice infected with the
avirulent encapsulated strain P15986 or the avirulent unencapsulated strain R6
died. After collection of lung lavage cells and nuclear extraction, NF-kappaB
activation was determined 1 hr, 4 hrs, 6 hrs and 24 hrs after pneumococcal
infection. At the same time, pulmonary and blood clearance, bronchoalveolar
lavage cells population, and tumor necrosis factor-alpha production were assessed
(six mice per time point). MEASUREMENTS AND MAIN RESULTS: NF-kappaB was
constitutively expressed within nuclear extracts of lung lavage cells from
uninfected control mice. A significant increase in NF-kappaB activation was
detected within 1 hr after injection of virulent lysed S. pneumoniae P4241 strain
(bacterial components equivalent to 4 x 10(5) CFU), and was still present 24 hrs
after the injection. After live pneumococcal challenge, significant NF-kappaB
activation was detected within 4 hrs with a peak at 24 hrs. Responses to all
three strains (P4241, P15986 and R6) were time-dependent (p < .0001), as NF
kappaB activation gradually increased during the first 24 hrs. Moreover, compared
with the control uninfected mice, the intensity of the retarded KB
oligonucleotide, as determined by densitometry, was increased approximately four-
to five-fold and seven-fold in reactions containing nuclear extracts isolated 24
hrs after infection with the avirulent strains P15986 or R6 and the virulent
strain P4241, respectively. With the virulent strain P4241, responses were
significantly stronger than with the avirulent strains P15986 and R6 (p < .01).
Responses were of similar order with avirulent strains P15986 and R6 (p > .05).
CONCLUSION: Pulmonary infection by S. pneumoniae induced delayed and time
dependent activation of NF-kappaB in mouse lung lavage cells. The degree of NF
kappaB activation in lung lavage cells correlated with the virulence of the
infecting organisms. Our results suggest that the more severe the infection, the
higher the rise in NF-kappaB.
PMID- 11008991
TI - CO2 reactivity and brain oxygen pressure monitoring in severe head injury.
AB - OBJECTIVE: To investigate the effect of hyperventilation on cerebral oxygenation
after severe head injury. DESIGN: A prospective, observational study. SETTING:
Neurointensive care unit at a university hospital. PATIENTS: A total of 90
patients with severe head injury (Glasgow Coma Scale score < or =8), in whom
continuous monitoring of brain tissue oxygen pressure (PbrO2) was performed as a
measure of cerebral oxygenation. INTERVENTIONS: Arterial PCO2 was decreased each
day over a 5-day period for 15 mins by increasing minute volume on the ventilator
setting to 20% above baseline. Arterial blood gas analysis was performed before
and after changing ventilator settings. Multimodality monitoring, including
PbrO2, was performed in all patients. Absolute and relative PbrO2/PaCO2
reactivity was calculated. Outcome at 6 months was evaluated according to the
Glasgow Outcome Scale. MEASUREMENTS AND MAIN RESULTS: Effective hyperventilation,
defined by a decrease of PaCO2 > or =2 torr (0.27 kPa), was obtained in 218 (84%)
of 272 tests performed. Baseline PaCO2 averaged 32.3 +/- 4.5 torr (4.31 +/- 0.60
kPa). Average reduction in PaCO2 was 3.8 +/- 1.7 torr (0.51 +/- 0.23 kPa). PbrO2
decreased by 2.8 +/- 3.7 torr (0.37 +/- 0.49 kPa; p < .001) from a baseline value
of 26.5 +/- 11.6 torr (3.53 +/- 1.55 kPa). PbrO2/PaCO2 reactivity was low on day
1 (0.8 +/- 2.3 torr [0.11 +/- 0.31 kPa]), increasing on subsequent days to 6.1 +/
4.4 torr (0.81 +/- 0.59 kPa) on day 5. PbrO2/PaCO2 reactivity on days 1 and 2
was not related to outcome. In later phases in patients with unfavorable outcome,
relative reactivity was increased more markedly, reaching statistical
significance on day 5. CONCLUSIONS: Increased hyperventilation causes a
significant reduction in PbrO2, providing further evidence for possible increased
risk of secondary ischemic damage during hyperventilation. The low PbrO2/PaCO2
reactivity on day 1 indicates the decreased responsiveness of cerebral
microvascular vessels to PaCO2 changes, caused by generalized vascular narrowing.
The increasing PbrO2/PaCO2 reactivity from days 2 to 5 suggests that the risk of
compromising cerebral oxygenation by hyperventilation may increase over time.
PMID- 11008990
TI - Comparison between selective and nonselective nitric oxide synthase inhibition
and phenylephrine in normal and endotoxic swine.
AB - OBJECTIVE: To compare the cardiopulmonary and peripheral circulatory effects of
the nonselective nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl
ester (L-NAME) to the more selective inducible NOS inhibitor S-methylisothiourea
(SMT) and to phenylephrine (PE) in endotoxic and normal swine. DESIGN:
Prospective, randomized, unblinded study. SETTING: Research laboratory of
academic medical center. SUBJECTS: Nonanesthetized, sedated, mechanically
ventilated, minimally invasive swine model. INTERVENTIONS: Animals received
either lipopolysaccharide (LPS, LPS groups) or equivalent volume of saline
(normal groups). LPS animals were further randomized into four groups when mean
arterial pressure (MAP) had dropped to <60 mm Hg: the LPS/saline group received
saline only; the other groups received either L-NAME, SMT, or PE. These were
titrated to elevate MAP by 20-25 mm Hg, and animals were followed for another 3
hrs. Pulmonary artery occlusion pressure was maintained at one to two times
baseline with the infusion of saline. Normal groups received the same agents 1 hr
after baseline measurements, and drugs were titrated to achieve similar increases
in MAP. We measured gastric-arterial PCO2 gradient by tonometry as an index of
gastric mucosal perfusion. Left ventricular volumes were determined
echocardiographically; right ventricular volumes were determined by a pulmonary
arterial catheter equipped with a rapid thermistor. Plasma nitrite/nitrate (NOx)
concentrations were measured hourly. MEASUREMENTS AND MAIN RESULTS: In the LPS
groups, all agents elevated MAP and systemic vascular resistance similarly. By hr
4, cardiac output had decreased in all groups, but the decrease with L-NAME (35%
+/- 16%) occurred earlier (at hr 3) and was larger than the decrease with SMT at
hrs 3 and 5 and larger than the decrease with saline at hrs 3 to 5. L-NAME
resulted in a larger increase in mean pulmonary arterial pressure (MPAP) when
compared with saline (130% +/- 44% vs. 61% +/- 25%; p < .001) and SMT groups
(130% vs. 97% +/- 80%; p < .007). Only L-NAME had detrimental effects on right
ventricular function as indicated by an increase in right ventricular end
systolic volume (54 +/- 10 to 87 +/-6 mL; p < .05) and right ventricular end
diastolic volume (90 +/-11 to 128 +/- 18 mL; p < .05). SMT decreased both left
ventricular end-systolic volume (10.4 +/- 2 to 7.7 +/- 4 mL; p < .05) and left
ventricular end-diastolic volume (18.5 +/- 3 to 14.2 +/- 5 mL; p < .05),
indicating improved left ventricular function, whereas L-NAME did not affect left
ventricular volumes. Both SMT and PE corrected LPS-induced gastric mucosal
acidosis, but L-NAME did not. We did not detect changes in plasma NOx
concentrations in any of LPS groups. In the normal groups, all agents increased
MAP without changes in plasma NOx concentrations. L-NAME caused a larger decrease
in cardiac output, but the increase in MPAP was higher with SMT. Both NOS
inhibitors led to left ventricular dilation, but PE did not. Only L-NAME caused
right ventricular dilation. There were no changes in gastric-arterial PCO2
gradient. CONCLUSIONS: In LPS animals, we failed to detect changes in plasma NOx
concentrations. Furthermore, for similar increases in MAP, SMT improved gastric
mucosal acidosis, had less adverse effects on right ventricular function and
MPAP, and may have improved left ventricular function. However, apart from its
bene-ficial effects on left ventricular function, SMT was not superior to PE. The
results from normal animals indicate that both NOS inhibitors have adverse
effects on cardiac function beyond those attributed to increased MAP.
PMID- 11008992
TI - Measurements of cortical cellular pH by intracranial tonometer in severe head
injury.
AB - OBJECTIVE: To evaluate the cortical cellular damage in acute severe head injury,
we measured the cortical cellular pH by using an intracranial tonometer made in
our institution. DESIGN: Prospective, 3.5-yr data collection. SETTING: University
hospital trauma intensive care unit. PATIENTS: Severely head-injured patients (n
= 29) with Glasgow Coma Scale score <8. INTERVENTION: Routine emergency
neurologic procedure. MEASUREMENTS AND MAIN RESULTS: We made 98 measurements of
cortical cellular pH by intracranial tonometer in 29 severely head-injured
patients in the acute phase. Each patient's intracranial pressure was recorded,
and in 16 patients, the saturation of jugular venous oxygen was monitored. The
outcome at 6 months after injury was significantly better in patients having a
cortical cellular pH of >7.2 than those with <7.2. The cerebral perfusion
pressure and cortical cellular pH correlated significantly (p < .0001).
CONCLUSIONS: Our study suggests the usefulness of measurement of cortical
cellular pH by intracranial tonometer for evaluating the severity of focal
anaerobic cerebral metabolism and predicting patient prognosis.
PMID- 11008993
TI - Experience and endocrine stress responses in neonatal and pediatric critical care
nurses and physicians.
AB - OBJECTIVE: Critical care is a working environment with frequent exposure to
stressful events. High levels of psychological stress have been associated with
increased prevalence of burnout. Psychological distress acts as a potent trigger
of cortisol secretions. We attempted to objectify endocrine stress reactivity.
DESIGN: Observational cohort study during two 12-day periods in successive years.
SETTING: A tertiary multidisciplinary neonatal and pediatric intensive care unit
(33 beds). SUBJECTS: One hundred and twelve nurses and 27 physicians (94% accrual
rate). INTERVENTIONS AND MEASUREMENTS: Cortisol determined from salivary samples
collected every 2 hrs and after stressful events. Participants recorded the
subjective perception of stress with every sample. Endocrine reactions were
defined as transient surges in cortisol of >50% and 2.5 nmol/L over the baseline.
MAIN RESULTS: During 7,145 working hours, we observed 474 (12.5%) endocrine
reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L
(219%). The mean occurrence rate of endocrine reactions per subject and sample
was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in
experienced team members (>3 yrs of intensive care vs. <3 yrs, 4.1 vs. 4.95
nmol/L, p < .001), professional experience failed to attenuate the frequency and
magnitude of endocrine reactions, except for the subgroup of nurses and
physicians with >8 yrs of intensive care experience. A high proportion (71.3%) of
endocrine reactions occurred without conscious perception of stress. Unawareness
of stress was higher in intensive care nurses (75.1%) than in intermediate care
nurses (51.8%, p < .01). CONCLUSIONS: Stress-related cortisol surges occur
frequently in neonatal and pediatric critical care staff. Cortisol increases are
independent of subjective stress perception. Professional experience does not
abate the endocrine stress reactivity.
PMID- 11008994
TI - A controlled trial of cardiopulmonary resuscitation training for ethnically
diverse parents of infants at high risk for cardiopulmonary arrest.
AB - OBJECTIVE: Parents of infants hospitalized in the neonatal intensive care unit
are routinely taught cardiopulmonary resuscitation (CPR) as part of the
preparation for transition to home. A variety of methods are used to teach CPR
knowledge and skills. The purpose of this study was to compare the psychosocial
consequences of three different methods of CPR training for parents of infants at
high risk for cardiopulmonary arrest. DESIGN, SETTING, AND SUBJECTS: In this
prospective, multisite clinical trial, 335 parents and other caretakers of
infants hospitalized in the neonatal intensive care unit were followed for 1 yr.
Participants were 69% female, 49% Latino/Latina, with a mean age of 30 +/- 8 yrs.
INTERVENTION: Subjects initially were randomized to one of four CPR training
protocols: a video-only class, an instructor-taught class, an instructor-taught
class combined with a social support intervention, and a control group. The
social support intervention involved a group discussion after CPR training with
regular telephone follow-up over the next 6 months by a nurse. MEASUREMENTS AND
MAIN RESULTS: Data on psychosocial adjustment to illness, anxiety, and depression
were collected at baseline, 2 wks, and 3 and 6 months. There were significant
differences among the groups over time in anxiety (p = .007) and psychosocial
adjustment to illness (p = .001). Parents in the CPR-video protocol had
significantly less early anxiety and better postdischarge psychosocial adjustment
compared with parents in the social support intervention at 2 wks after hospital
discharge. Patterns of change over time, however, supported the efficacy of the
CPR-social support intervention or the CPR-instructor protocols when compared
with the CPR-video protocol. CONCLUSION: The results confirm that parents have
difficulty adjusting after an infant's discharge from the neonatal intensive care
unit and support the positive psychosocial effects of helping parents prepare for
a home emergency by teaching CPR. The additional staff resources required to
provide parents with social support along with CPR training are not justified
based on the findings of the current study.
PMID- 11008995
TI - Outcome of cardiopulmonary resuscitation in a pediatric cardiac intensive care
unit.
AB - OBJECTIVE: To determine the eventual outcome of children with heart disease who
had cardiopulmonary resuscitation (CPR) in a specialized pediatric cardiac
intensive care unit (CICU), and to define the influence of any prearrest
variables on the outcome. DESIGN: A retrospective review of patients' medical
records. SETTING: A pediatric CICU of a tertiary pediatric teaching hospital.
PATIENTS AND METHODS: Patients were all children who presented with
cardiopulmonary arrest and who were administered CPR in the pediatric CICU
between June 1995 and June 1997. Prearrest variables such as age, diagnosis,
prior cardiac surgery, and inotropic support with epinephrine, as well as cause
of arrest, were evaluated. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients,
ranging in age from 1 day to 21 yrs (median, 1 month), satisfied criteria for
inclusion in the study group. These 32 patients had a total of 38 episodes of
cardiopulmonary arrest. Twenty-five of these patients (78%) had cardiac surgery
before arrest. Inotropic support with continuous infusion of epinephrine was
being administered at the time of arrest in 18 of 38 (47%) arrests. These
prearrest variables did not influence outcome of CPR. Of the 38 episodes of CPR,
24 episodes (63%) were successful, with 20 episodes resulting in return of
spontaneous circulation and four patients being successfully placed on mechanical
cardiopulmonary support. Fourteen children, including all four patients who were
rescued with mechanical cardiopulmonary support, survived to discharge. At 6
month follow-up, 11 patients were still alive, with three having neurologic
impairment. CONCLUSIONS: After cardiopulmonary resuscitation in this pediatric
CICU, the rate of success was 63% and the rate of survival was 42%. Prior cardiac
surgery and use of epinephrine before arrest did not influence the outcome of
CPR. The availability of effective mechanical cardiopulmonary support can improve
the outcome of CPR.
PMID- 11008996
TI - Use of hypertonic saline solutions in treatment of cerebral edema and
intracranial hypertension.
AB - OBJECTIVES: To review the literature on the use of hypertonic saline (HS) in
treating cerebral edema and intracranial hypertension. DATA SOURCES: Review of
scientific and clinical literature retrieved from a computerized MEDLINE search
from January 1965 through November 1999. STUDY SELECTION: Pertinent literature is
referenced, including clinical and laboratory investigations, to demonstrate
principles and efficacy of treatment with HS in patients with intracranial space
occupying pathology. DATA EXTRACTION: The literature was reviewed to summarize
the mechanisms of action, efficacy, adverse effects, systemic effects, and
comparisons with standard treatments in both clinical and laboratory settings.
DATA SYNTHESIS: HS has an osmotic effect on the brain because of its high
tonicity and ability to effectively remain outside the bloodbrain barrier.
Numerous animal studies have suggested that fluid resuscitation with HS bolus
after hemorrhagic shock prevents the intracranial pressure (ICP) increase that
follows resuscitation with standard fluids. There may be a minimal benefit in
restoring cerebral blood flow, which is thought to be mitigated through local
effects of HS on cerebral microvasculature. In animal models with cerebral
injury, the maximum benefit is observed in animals with focal injury associated
with vasogenic edema (cryogenic injury). The ICP reduction is seen for < or =2
hrs and may be maintained for longer periods by using a continuous infusion of
HS. The ICP reduction is thought to be caused by a reduction in water content in
areas of the brain with intact blood-brain barrier such as the nonlesioned
hemisphere and cerebellum. Most comparisons with mannitol suggest almost equal
efficacy in reducing ICP, but there is a suggestion that mannitol may have a
longer duration of action. Human studies published to date reporting on the use
of HS in treating cerebral edema and elevated ICP include case reports, case
series, and small controlled trials. Results from studies directly comparing HS
with standard treatment in regard to safety and efficacy are inconclusive.
However, the low frequency of side effects and a definite reduction of ICP
observed with use of HS in these studies are very promising. Systemic effects
include transient volume expansion, natriuresis, hemodilution, immunomodulation,
and improved pulmonary gas exchange. Adverse effects include electrolyte
abnormalities, cardiac failure, bleeding diathesis, and phlebitis. Although
unproven, a potential for central pontine myelinolysis and rebound intracranial
hypertension exists with uncontrolled administration. CONCLUSIONS: HS
demonstrates a favorable effect on both systemic hemodynamics and intracranial
pressure in both laboratory and clinical settings. Preliminary evidence supports
the need for controlled clinical trials evaluating its use as resuscitative fluid
in brain-injured patients with hemorrhagic shock, as therapy for intracranial
hypertension resistant to standard therapy, as firstline therapy for intracranial
hypertension in certain intracranial pathologies, as small volume fluid
resuscitation during spinal shock, and as maintenance intravenous fluid in
neurocritical care units.
PMID- 11008997
TI - Thirty years of clinical trials in acute respiratory distress syndrome.
AB - OBJECTIVE: To systematically review clinical trials in acute respiratory distress
syndrome (ARDS). DATA SOURCES: Computerized bibliographic search of published
research and citation review of relevant articles. STUDY SELECTION: All clinical
trials of therapies for ARDS were reviewed. Therapies that have been compared in
prospective, randomized trials were the focus of this analysis. DATA EXTRACTION:
Data on population, interventions, and outcomes were obtained by review. Studies
were graded for quality of scientific evidence. MAIN RESULTS: Lung protective
ventilator strategy is supported by improved outcome in a single large,
prospective trial and a second smaller trial. Other therapies for ARDS, including
noninvasive positive pressure ventilation, inverse ratio ventilation, fluid
restriction, inhaled nitric oxide, almitrine, prostacyclin, liquid ventilation,
surfactant, and immune-modulating therapies, cannot be recommended at this time.
Results of small trials using corticosteroids in late ARDS support the need for
confirmatory large clinical trials. CONCLUSIONS: Lung protective ventilator
strategy is the first therapy found to improve outcome in ARDS. Trials of prone
ventilation and fluid restriction in ARDS and corticosteroids in late ARDS
support the need for large, prospective, randomized trials.
PMID- 11008998
TI - Prevention of nosocomial bloodstream infections: effectiveness of antimicrobial
impregnated and heparin-bonded central venous catheters.
AB - OBJECTIVES: To examine the effectiveness of antimicrobial-impregnated and heparin
bonded catheters relative to standard central venous catheters in lessening
catheter-related bloodstream infections. DATA SOURCES: Articles were identified
by computer-assisted searching. STUDY SELECTION: Studies were eliminated from
further consideration if they did not contain original data relevant to lessening
catheter-related bloodstream infections, were nonrandomized or uncontrolled,
described subjects <17 yrs of age, or used animal subjects. DATA ABSTRACTION:
From each eligible article, we abstracted the following: a) citation; b) type of
control; c) study setting; d) type of experimental catheter; e) catheter-specific
complications; f) total numbers of patients and catheters; g) number of
experimental catheters used that resulted in a catheter-related bloodstream
infection; h) number of control catheters used that resulted in a catheter
related bloodstream infection; i) number of experimental catheters used without
catheter-related bloodstream infections; and j) number of control catheters used
without infections. We also recorded the duration of catheter use and the types
of microbes cultured in association with the catheters and with catheter-related
bloodstream infections. DATA SYNTHESIS: Eleven eligible studies were identified.
Using meta-analysis, we showed that antimicrobial-impregnated and heparin-bonded
central venous catheters significantly decreased catheter-related bloodstream
infections by 2.32% (95% confidence interval, 1.04% to 3.61%). CONCLUSIONS: The
modest additional cost for the use of these catheters relative to the
considerable cost of treating even a single bloodstream infection makes their use
cost-effective.
PMID- 11008999
TI - How to respond to family demands for futile life support and cardiopulmonary
resuscitation.
PMID- 11009000
TI - Reactive hemophagocytic syndrome presenting as a component of multiple organ
dysfunction syndrome.
AB - OBJECTIVE: To report two cases of severe reactive hemophagocytic syndrome (RHS),
to discuss their impact, and to present evidence that RHS may be a constitutive
part of multiple organ dysfunction syndrome (MODS). DESIGN: Case-report. SETTING:
Pediatric intensive care unit (PICU). PATIENTS: Two patients with RHS and MODS.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Case #1: A 3 yr-old boy with
Mucha-Haberman syndrome (pityriasis lichenoides) was admitted to the PICU for
septic shock, acute respiratory distress syndrome, capillary leak, acute renal
failure, liver dysfunction, and RHS (pancytopenia and hemophagocytosis on bone
marrow aspirate). The pancytopenia was severe (white blood cell count, 0.9 x
10(9)/L; hemoglobin, 59 g/L; platelets, 36 x 10(9)/L), required many
transfusions, and resolved 2 months later. The patient needed mechanical
ventilation for 6 wks. Length of stay in PICU was 2 months. Case #2: A previously
healthy 4 yr-old girl was admitted to the PICU for respiratory failure. She
developed acute respiratory distress syndrome, cardiomyopathy with complete
atrioventricular block, shock, capillary leak, liver dysfunction, and RHS
(pancytopenia and hemophagocytosis on bone marrow aspirate). The pancytopenia was
severe (white blood cell count, 1.92 x 10(9)/L; hemoglobin, 65 g/L; platelets, 58
x 10(9)/L) and necessitated transfusional support. Serology for respiratory
syncytial virus was positive. RHS duration was 20 days; the patient recovered
completely. Length of mechanical ventilation was 16 days and length of stay in
PICU was 3 wks. CONCLUSIONS: These cases show that RHS may be a significant cause
of pancytopenia in the PICU. It needs to be recognized as a clinical entity
because it can be reversible and nonneoplastic. RHS and MODS share some
pathophysiologic elements and could be related to each other.
PMID- 11009001
TI - Hemoperfusion is ineffectual in severe chloroquine poisoning.
AB - OBJECTIVES: To study the toxicokinetics in severe chloroquine poisoning, and to
evaluate the efficacy of hemoperfusion. DESIGN: Case report on one observation.
SETTING: Medical intensive care unit (ICU) of the University Medical Center
Utrecht, The Netherlands. PATIENT HISTORY: A previously healthy, 52-yr-old woman
ingested 100 tablets containing 100 mg chloroquine base 1 hr before admission. At
admission, she was drowsy, agitated, hypotensive, and in respiratory distress.
Shortly thereafter, she was resuscitated from cardiac arrest. After hemodynamic
and respiratory stabilization, the patient was transferred to the medical ICU.
TOXICOKINETICS EVALUATION: During the course of her stay at the ICU, blood
samples were taken for the determination of chloroquine and the metabolite
desethylchloroquine concentration. Hemoperfusion was started 3.5 hrs after
ingestion of the chloroquine tablets. MEASUREMENTS AND MAIN RESULTS: The
following toxicokinetics data during this severe chloroquine poisoning were
calculated: apparent volume of the central compartment 181 L, apparent volume of
distribution 1137 L, half-life in the distribution phase 6.4 hrs, half-life in
the elimination phase 392.8 hrs, and total body clearance 2.01 L/hour. The
average extraction ratio during hemoperfusion was 0.07, 0.28, and 0.25, in
plasma, erythrocytes and whole blood, respectively. The total amount of
chloroquine removed by hemoperfusion was only 480 mg (5.3% of the amount
ingested). Simulation of a hemoperfusion session over 5 hrs by using a column
with an optimal extraction ratio of 1.0 would have removed 1,816 mg chloroquine,
only 18.2% of the amount ingested. This limited contribution of hemoperfusion to
the total clearance makes it ineffective. CONCLUSION: Hemoperfusion is not
effective in severe chloroquine poisoning, even when started (relatively) early
in the course of the intoxication. Toxicokinetic evaluation of a chloroquine
poisoning should be based on the evaluation of plasma and whole blood
concentrations.
PMID- 11009002
TI - Acute respiratory distress syndrome and protein: gold or flash in the pan?
PMID- 11009003
TI - Optimizing the utilization of Advance Directives.
PMID- 11009004
TI - Surgical models of acute lung injury.
PMID- 11009005
TI - Thoracoabdominal aortic aneurysm repair: a human model of ischemia/reperfusion
induced cytokine-driven multiple organ dysfunction syndrome.
PMID- 11009006
TI - Another piece of the pathobiological puzzle in the response to trauma.
PMID- 11009007
TI - Treatment of secondary ischemic insults after traumatic brain injury.
PMID- 11009008
TI - Mucosal blood flow: acting globally but we should be thinking locally.
PMID- 11009009
TI - Hyperventilation in severe brain injury revisited.
PMID- 11009010
TI - The well-stressed intensivist.
PMID- 11009011
TI - Are educational interventions enough for retention of cardiopulmonary
resuscitation techniques?
PMID- 11009012
TI - Cardiopulmonary resuscitation outcomes in children.
PMID- 11009013
TI - Antimicrobial catheters: value and safety.
PMID- 11009014
TI - Prediction of postoperative cardiac surgical morbidity and organ failure at
admission to the intensive care unit using esophageal Doppler ultrasonography.
PMID- 11009015
TI - Is surgical tracheostomy really superior to percutaneous tracheostomy?
PMID- 11009016
TI - Percutaneous versus open tracheostomy: is it a fair comparison?
PMID- 11009017
TI - Bedside percutaneous versus open tracheostomy.
PMID- 11009018
TI - Steroids in cardiopulmonary bypass.
PMID- 11009019
TI - Monitoring of peripheral nerves and muscle function in patients with multiple
organ dysfunction syndrome.
PMID- 11009020
TI - Saline-based fluids can cause a significant acidosis that may be clinically
relevant.
PMID- 11009021
TI - Dilutional acidosis.
PMID- 11009022
TI - Venous air embolism from central venous catheterization: under-recognized or over
diagnosed?
PMID- 11009023
TI - Breath of life and cardiopulmonary resuscitation.
PMID- 11009024
TI - Liquid adsorption chromatography of polyethers: experiments and simulation.
AB - The adsorption behavior of poly(ethylene glycol) (PEG) in reversed-phase
chromatography is studied both experimentally and theoretically and a computer
simulation of chromatograms is performed on the basis of these studies. The
experimental conditions were: different reversed-phase adsorbents and a solvent
methanol-water system as the mobile phase. At varying mobile phase compositions
highly resolved chromatograms of PEG samples were obtained, in which all peaks
could be identified, and the dependencies of the distribution coefficient on the
degree of polymerization for PEG molecules were evaluated by processing these
chromatograms. The data were interpreted by using a theory of homopolymers based
on a continuum Gaussian chain model of flexible macromolecules and a slit-like
model of pores of stationary phase. The theory proved to describe well the
experimental data in the whole range of studied molecular masses, and the
thermodynamic parameters characterizing interactions of ethylene oxide repeating
units in PEG molecules with the adsorbent pore walls have been determined from
the comparison of the theory with the experimental data. The dispersion of
chromatographic peaks corresponding to individual oligomer molecules is also
estimated. In the system studied the peak width occurred to be proportional to
the distribution coefficient of corresponding macromolecule. The theory is used
to develop a computer-assisted procedure for simulation of chromatograms for
samples of linear homopolymers. Using the obtained data on the thermodynamic
parameters and the estimates of peak dispersion, chromatograms are simulated for
PEG samples at two different chromatographic conditions. These simulated
chromatograms were in good quantitative agreement with the real chromatograms.
PMID- 11009025
TI - Determination of the lumped mass transfer rate coefficient by frontal analysis.
AB - The validity of measurements of the lumped mass transfer rate coefficient (km,L)
is studied on the basis of experimental data acquired under Langmuir isotherm
conditions, in reversed-phase liquid chromatography. Two different methods were
used, the perturbation method and frontal analysis. Accurate values of km,L can
be properly obtained by the perturbation method because, with this method, the
chromatographic processes take place under locally linear isotherm conditions.
Values of km,L can also be derived from the breakthrough curves obtained in
frontal analysis. Because the contribution of axial dispersion to band broadening
was larger than that of the mass transfer resistances, the apparent axial
dispersion coefficient (Da) was first derived from the breakthrough curve by
applying the equilibrium-dispersive model. Then, the value of km,L was calculated
from Da. The values of km,L determined by the two methods were in close agreement
in the range of nondimensional Langmuir equilibrium constants (r= 1/[1+KLC0])
between 0.32 and 0.85, irrespective of the mobile phase flow velocity. Thus,
frontal analysis can be used for kinetic studies of the mass transfer in
chromatographic columns.
PMID- 11009026
TI - Solid-phase extraction of polar hydrophilic aromatic sulfonates followed by
capillary zone electrophoresis-UV absorbance detection and ion-pair liquid
chromatography-diode array UV detection and electrospray mass spectrometry.
AB - A comprehensive comparison of four different polymeric solid-phase extraction
(SPE) materials for the extraction of 22 different aromatic sulfonates of
environmental concern was performed. The investigated adsorbents were the
polystyrene-divinylbenzene materials LiChrolut EN from Merck, Isolute ENV+ from
International Sorbent Technology, HR-P from Macherey-Nagel and the new Oasis HLB
poly(divinylbenzene-co-N-vinylpyrrolidone) copolymer from Waters. Different SPE
parameters like the elution solvent and the drying step of the cartridges were
optimized. Analyses were performed by capillary zone electrophoresis-UV
absorbance detection (CZE-UV) and ion-pair liquid chromatography-diode array UV
detection coupled in series with electrospray mass spectrometry (IP-LC-DAD-ESI
MS) in the negative ionization mode. LC-MS offers a higher separation efficiency
than CZE. The best adsorbents were LiChrolut EN and HR-P followed by Isolute ENV+
and Oasis HLB. The recoveries for most of the onefold negatively charged aromatic
sulfonates were >50% for the extraction from spiked ground water at 50 microg/l.
Recoveries for LiChrolut EN and HR-P were approximately 20% higher than for
Isolute ENV+. Very hydrophilic sulfonates containing more than one negative
sulfonate group could not be extracted by any of the tested adsorbents.
PMID- 11009027
TI - Determination of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high
performance liquid chromatography coupled to evaporative light scattering
detection.
AB - A method for the separation and quantitation of the enantiomers of 3-tert.
butylamino-1,2-propanediol by high-performance liquid chromatography and
evaporative light scattering detection has been developed. Separation of the
enantiomers was performed in normal-phase liquid chromatography on a Chiralpak AS
chiral stationary phase. The influence of the gas nature, gas pressure and
temperature of the drift tube of the evaporative light scattering detector on the
detection sensitivity was investigated. The method was validated in terms of
linearity, limit of quantitation, accuracy and precision. The enantiomeric excess
of (S)-3-tert.-butylamino-1,2-propanediol, used for the industrial synthesis of
(S)-timolol, was measured from 0 to 94%.
PMID- 11009028
TI - Fractionation of apple procyanidins according to their degree of polymerization
by normal-phase high-performance liquid chromatography.
AB - A new method was developed for the fractionation of procyanidin oligomers
according to their degree of polymerization. Monomeric flavan-3-ols and low
molecular mass procyanidins were selectively extracted from the lyophilized
powder of apple condensed tannins (ACTs) by methyl acetate extraction.
Sequentially, the separation of each oligomer from dimer to pentamer in this
extract was carried out by normal-phase high-performance liquid chromatography
using a silica-beads packed column. The best separation was achieved with a
mobile phase system containing hexane; (1) hexane-methanol-ethyl acetate, (2)
hexane-acetone. These sequential treatments can be easily adapted to large-scale
fractionation.
PMID- 11009029
TI - Reinforcement of frontal affinity chromatography for effective analysis of lectin
oligosaccharide interactions.
AB - Frontal affinity chromatography is a method for quantitative analysis of
biomolecular interactions. We reinforced it by incorporating various merits of a
contemporary liquid chromatography system. As a model study, the interaction
between an immobilized Caenorhabditis elegans galectin (LEC-6) and fluorescently
labeled oligosaccharides (pyridylaminated sugars) was analyzed. LEC-6 was coupled
to N-hydroxysuccinimide-activated Sepharose 4 Fast Flow (100 microm diameter),
and packed into a miniature column (e.g., 10 x 4.0 mm, 0.126 ml). Twelve
pyridylaminated oligosaccharides were applied to the column through a 2-ml sample
loop, and their elution patterns were monitored by fluorescence. The volume of
the elution front (V) determined graphically for each sample was compared with
that obtained in the presence of an excess amount of hapten saccharide, lactose
(V0); and the dissociation constant, Kd, was calculated according to the
literature [K. Kasai, Y. Oda, M. Nishikawa, S. Ishii, J. Chromatogr. 376 (1986)
33]. This system also proved to be useful for an inverse confirmation; that is,
application of galectins to an immobilized glycan column (in the present case,
asialofetuin was immobilized on Sepharose 4 Fast Flow), and the elution profiles
were monitored by fluorescence based on tryptophan. The relative affinity of
various galectins for asialofetuin could be easily compared in terms of the
extent of retardation. The newly constructed system proved to be extremely
versatile. It enabled rapid (analysis time 12 min/cycle) and sensitive (20 nM for
pyridylaminated derivatives, and 1 microg/ml for protein) analyses of lectin
carbohydrate interactions. It should become a powerful tool for elucidation of
biomolecular interactions, in particular for functional analysis of a large
number of proteins that should be the essential issues of post-genome projects.
PMID- 11009031
TI - Post-column oxidative derivatization for the liquid chromatographic determination
of phenothiazines.
AB - A first post-column chemical derivatization method for the liquid chromatographic
determination of phenothiazines is presented. Peroxyacetic acid is introduced as
a derivatizing agent for phenothiazines, yielding the colored radical cations or
fluorescent sulfoxides, depending on reaction conditions. Both reaction products
were successfully employed for the detection of the phenothiazines after their
liquid chromatographic separation. The fluorescence spectroscopic detection of
the sulfoxides proved to be the more robust and sensitive method. Limits of
detection ranged from 4 nM for triflupromazine and trimeprazine to 300 nM for
phenothiazine for the fluorescence spectroscopic detection of the sulfoxide and
from 0.3 microM for phenothiazine and triflupromazine to 2 microM for
trifluperazine for the UV-Vis spectroscopic detection of the radical cation. The
calibration functions for the fluorimetric sulfoxide determination ranged from
two to more than three decades, starting at the limit of quantification.
PMID- 11009030
TI - Validation of an analysis method for 4-amino-3-hydroxybutyric acid by reversed
phase liquid chromatography.
AB - A rapid and simple reversed-phase liquid chromatographic method that did not
require the derivatization of 4-amino-3-hydroxybutyric acid (GABOB) was developed
and validated. The method proved to be suitable for the determination of GABOB
concentrations in finished pharmaceutical product (tablets). The method was
developed using a RP-18 column, UV detection at 210 nm and 0.01 M sodium
heptasulphonate solution, at pH 2.4, as the mobile phase. Different validation
parameters were included and satisfactorily evaluated. The specificity of the
method was demonstrated. Linearity was established in the range 0.40-0.60 mg/ml
(r=0.997). The method showed excellent accuracy (100.1%). Precision
(repeatability) gave a relative standard deviation value of 0.68%, while the
intermediate precision was 1.70%. A robustness test showing the influence of
different pH values and counter-ion concentrations was also performed.
PMID- 11009032
TI - Determination of naphthalenesulfonates in water by on-line ion-pair solid-phase
extraction and ion-pair liquid chromatography with fast-scanning fluorescence
detection.
AB - A fast analytical method for quantifying a mixture of 12 naphthalenesulfonates
and naphthalenedisulfonates has been developed. This method consists of on-line
ion-pair solid-phase extraction with PLRP-s sorbent and ion-pair liquid
chromatography using fast-scanning fluorescence spectrometer as a detection
system and multivariate calibration. As complete separation is unnecessary, the
compounds were analysed in isocratic conditions and the chromatographic analysis
took only 25 min. Three-way partial least-squares (PLS) was used to carry out
multivariate calibration for spiked tap water. In these conditions,
quantification limits were between 0.01 and 3 microg x l(-1). Repeatability was
also evaluated and relative standard deviations (n=3) were between 0.5 and 4,
depending on the compound. Finally, spiked tap and Ebro river waters were
analysed to evaluate prediction capability of the method.
PMID- 11009033
TI - Simultaneous determination of inorganic disinfection by-products and the seven
standard anions by ion chromatography.
AB - For the first time, an ion chromatographic method for the simultaneous
determination of the disinfection by-products bromate, chlorite, chlorate, and
the so-called seven standard anions, fluoride, chloride, nitrite, sulfate,
bromide, nitrate and orthophosphate is presented. The separation of the ten
anions was carried out using a laboratory-made high-capacity anion-exchanger. The
high capacity anion-exchanger allowed the direct injection of large sample
volumes without any sample pretreatment, even in the case of hard water samples.
For quantification of fluoride, chloride, nitrite, sulfate, bromide, nitrate,
orthophosphate and chlorate, a conductivity detection method was applied after
chemical suppression. The post-column reaction, based on chlorpromazine, was
optimized for the determination of chlorite and bromate. The method detection
limit for bromate measured in deionized water is 100 ng/l and for chlorite, it is
700 ng/l. In hard drinking water, the method's detection limits are 700 ng/l
(bromate) and 3.5 microg/l (chlorite). The method's detection limits for the
other eight anions, determined by conductivity detection, are between 100
microg/l (nitrite) and 1.6 mg/l (chlorate).
PMID- 11009034
TI - Indirect analysis of urea herbicides from environmental water using solid-phase
microextraction.
AB - We described here a solid-phase microextraction procedure used to extract six
urea pesticides-- chlorsulfuron, fluometuron, isoproturon, linuron, metobromuron
and monuron--from environmental samples. Two polydimethylsiloxanes and a
polyacrylate fiber (PA) are compared. The extraction time, pH control, addition
of NaCl to the water and the influence of organic matter such as humic acid on
extraction efficiency were examined to achieve a sensitive method. Determination
was carried out by gas chromatography with nitrogen-phosphorus detection. The
proposed method requires the extraction of 2 ml of sample (pH 4, 14.3%, w/v,
NaCl) for 60 min with the PA fiber. The limits of detection range from 0.04 for
linuron to 0.1 microg/l for fluometuron and monuron and the relative standard
deviations at the 1 microg/l level are between 15% and 9%. The apparent fiber
water distribution constants (Kfw) calculated in the proposed conditions were in
the order of 10(3). Phenylurea herbicides were indirectly determined in the form
of their derived anilines and chlorsulfuron in the form of an aminotriazine as
confirmed by gas chromatography-mass spectrometry. Natural waters were utilized
to validate the final procedure. However, a unequivocal identification in unknown
environmental samples should be done by LC-MS. The presence of dissolved organic
matter such as humic acid produces losses during the extraction step. Adding
sodium chloride to the sample compensates for this effect.
PMID- 11009035
TI - Retention index database for identification of general green leaf volatiles in
plants by coupled capillary gas chromatography-mass spectrometry.
AB - A series of ubiquitously occurring saturated and monounsaturated six-carbon
aldehydes, alcohols and esters thereof is summarised as 'green leaf volatiles'
(GLVs). The present study gives a comprehensive data collection of retention
indices of 35 GLVs on commonly used non-polar DB-5, mid-polar DB-1701, and polar
DB-Wax stationary phases. Seventeen commercially not available compounds were
synthesised. Thus, the present study allows reliable identification of most known
GLV in natural plant volatile samples. Applications revealed the presence of
several seldom reported GLVs in headspace samples of mechanically damaged plant
leaves of Carpinus betulus and Fagus sylvatica.
PMID- 11009036
TI - Simulation of electrophoretic separations by the flux-corrected transport method.
AB - Electrophoretic separations at typical experimental electric field strengths have
been simulated by applying the flux-corrected transport (FCT) finite difference
method to the transient, one-dimensional electrophoresis model. The performance
of FCT on simulations of zone electrophoresis (ZE), isotachophoresis (ITP), and
isoelectric focusing (IEF) has been evaluated. An FCT algorithm, with a three
point, central spatial discretization, yields numerical solutions without
numerical oscillations or spurious peaks, which have plagued previously-published
second-order solutions to benchmark ZE and ITP problems. Moreover, the FCT
technique captures sharp zone boundaries and IEF peaks more accurately than
previously-published, first-order upwind schemes.
PMID- 11009037
TI - Pressurized-flow anion-exchange capillary electrochromatography using a polymeric
ion-exchange stationary phase.
AB - The feasibility of using capillary columns equipped with silica frits and packed
with a polymer-based anion exchanger (Dionex AS9-HC) for CEC separations of
inorganic anions has been investigated. Experiments using a conventional 25 cm
packed bed, and mobile phase flow that is a combination of hydrodynamic and
electroosmotic flow were used to demonstrate that by varying the applied voltage
(electrophoresis component) or the concentration of the competing ion in the
mobile phase (ion-exchange component), considerable changes in the separation
selectivity could be obtained. Using an artificial neural network, this
separation system was modelled and the results obtained used to determine the
optimum conditions (9 mM perchlorate and--10 kV) for the separation of eight
inorganic anions. When a short (8 cm) packed bed was used, with detection
immediately following the packed section, the separation of eight test analytes
in under 2.2 min was possible using pressure-driven flow and a simple step
voltage gradient. A more rapid separation of these analytes was obtained by only
applying high voltage (-30 kV), where many of the same analytes were separated in
less than 20 s and with a different separation selectivity to that obtained in
conventional ion-exchange or capillary electrophoresis separations.
PMID- 11009038
TI - Nonaqueous electrochromatography on continuous bed columns of sol-gel bonded
large-pore C18 material: separation of retinyl esters.
AB - A nonaqueous electrochromatographic reversed-phase separation method for retinyl
esters using continuous bed columns has been developed. The packing material 7
microm Nucleosil 4,000 angstroms C18 was sol-gel bonded in 180 microm I.D.
capillaries. The mobile phase used was 2.5 mM lithium acetate in N,N
dimethylformamide-acetonitrile-methanol (2+7+1, v/v). At 350 V/cm and 30 degrees
C, this mobile phase composition gave rise to an electroosmotic flow of 1 mm/s.
No Joule heating nor bubble formation were observed even at 625 V/cm (17 microA).
With a 36 cm L(eff) column complete separation of the commercially available and
synthesized standards (all-trans-retinyl acetate, palmitate, heptadecanoate,
stearate, oleoate, and linoleoate) was obtained within 10 min. The within-day and
between-day variations of retention times of all-trans-retinyl palmitate were
<0.3% relative standard deviation (RSD) (n=3) and <2% RSD (n=6), respectively.
The within-day and between-day variations of peak areas were both <2% (both n=3).
The columns were used for more than 1 month without degradation. Liver extracts
from arctic seal were analyzed.
PMID- 11009039
TI - New preconditioning strategy for the determination of inorganic anions with
capillary zone electrophoresis using indirect UV detection.
AB - It is widely accepted that preconditioning procedures are indispensable in
capillary electrophoresis in order to achieve reproducibility of migration times
and peak areas. Several preconditioning strategies have been employed for
electrophoretic determinations of inorganic anions using indirect UV detection
including simple flushing with buffer or alkaline or acid pre-rinsing followed by
flushing with electrolyte. We investigated the influence of various
preconditioning strategies on the reproducibility of migration times and peak
areas of inorganic anions. The electrolyte systems for indirect UV detection were
based on pyromellitic acid and chromic acid respectively as UV absorbing probes
and hexamethonium hydroxide as electroosmatic flow modifier. Preconditioning
agents under investigation were electrolyte buffer, NaOH, HCl and the free acids
of the UV absorbing probes. Investigations showed that reproducibility of
migration times and peak areas can be significantly improved by acid pre-rinsing
using the corresponding acid of the UV absorbing probes compared to
preconditioning by flushing the capillary with buffer. In contrast to acid pre
rinsing using hydrochloric acid no interfering signals within the migration time
window of inorganic anions under investigation can be observed. The optimized
preconditioning procedure yields relative standard deviations of migration times
less than 0.25% (n = 10). Relative standard deviations of corrected peak areas
were below 5% applying acid preconditioning using pyromellitic acid.
PMID- 11009040
TI - Potential of ethylenediaminedi(o-hydroxyphenylacetic acid) and N,N'
bis(hydroxybenzyl)ethylenediamine-N,N'-diacetic acid for the determination of
metal ions by capillary electrophoresis.
AB - Two aromatic polyaminocarboxylate ligands, ethylenediaminedi(o
hydroxyphenylacetic acid) (EDDHA) and N,N'-bis(hydroxybenzyl)ethylenediamine-N,N'
diacetic acid (HBED), were applied for the separation of transition and heavy
metal ions by the ion-exchange variant of electrokinetic chromatography. EDDHA
structure contains two chiral carbon centers. It makes it impossible to use the
commercially available ligand. All the studied metal ions showed two peaks, which
correspond to meso and rac forms of the ligand. The separation of metal-HBED
chelates was performed using poly(diallyldimethylammonium) polycations in mixed
acetate-hydroxide form. Simultaneous separation of nine single- and nine double
charged HBED chelates, including In(III), Ga(III), Co(II)-(III) and Mn(II)-(III)
pairs demonstrated the efficiency of 40,000-400,000 theoretical plates. The
separation of Co(III), Fe(III) complexes with different arrangements of donor
groups and oxidation of Co(II), Mn(H), Fe(II) ions in reaction with HBED have
been discussed.
PMID- 11009041
TI - Use of voltage gradient gel electrophoresis in apoptotic DNA analysis.
AB - In this paper the use of voltage gradient gel electrophoresis (VGGE) in the
electrophoretic analysis of apoptotic DNAs is described. The peculiarity of VGGE
fractionation in enhancing DNA bands in the gel by reducing their thickness was
used to obtain a rapid, more selective and higher-quality electrophoretic
fractionation of apoptotic DNA with respect to conventional electrophoresis. The
use of VGGE fractionations also allowed a reduced amount of DNA to be used to
detect a characteristic apoptotic DNA ladder pattern, in a lower agarose gel
concentration, with respect to conventional electrophoretic fractionation
PMID- 11009042
TI - The role of aminosalicylates at the beginning of the new millennium in the
treatment of chronic inflammatory bowel disease.
AB - OBJECTIVE: To discuss the pharmacological properties of aminosalicylates and
their potential value in the treatment of chronic inflammatory bowel disease
(IBD). METHODS: A review of clinical studies on the pharmacokinetics and mode of
action of aminosalicylates is provided. In addition, the clinical efficacy and
safety of aminosalicylates in the treatment of IBD, according to several recent
meta-analyses, is summarised. RESULTS: Whereas aminosalicylates represent drugs
of first choice in the acute treatment of ulcerative colitis and also for
maintaining those patients in remission, their value for patients with Crohn's
disease, either for achieving or maintaining remission, is at best modest. There
is a large variability in the clinical results, especially in Crohn's disease,
which is probably due to the variable extent and severity of IBD, different
instruments in the evaluation of therapeutic outcome, and also at least partly
caused by the different preparations and dosages of aminosalicylates used, as
well as the high variation in drug disposition and topical availability of the
active drug. The popular use of aminosalicylates is most likely due to the low
incidence of side effects and the good overall safety records of mesalazine
(mesalamine). CONCLUSIONS: Apparently, the full therapeutic potential of
aminosalicylates has not yet been evaluated (e.g. upper dosage range, combination
therapy, responding subgroups). Consequently, the imperfect treatment might be
improved in the new millennium by novel insights in the complex mode of action of
mesalazine as well as in the etiopathogenesis of IBD.
PMID- 11009044
TI - Evaluation of the readability of information sheets for healthy volunteers in
phase-I trials.
AB - OBJECTIVE: The aim of the present study was to assess whether information
sheets/consent forms submitted to the healthy volunteers of the Clinical
Pharmacology Unit (C.P.U.) panel at Glaxo-Wellcome (Verona, Italy) could be
considered understandable and to verify the readability and comprehensibility of
these documents. Since a volunteer bases his/her decision to take part in a study
on the information sheet provided, it is of paramount ethical importance to know
whether the sheet conveys all relevant information. In addition, a thorough
awareness by the volunteer of the reasons and procedures of the study would
increase compliance. METHODS: Four indices were used: Flesh-Vacca, Kincaid,
Gunning's Fog and Gulpease. All indices rate the degree of difficulty of a text,
in the light of the level of schooling of the target population. The documents
evaluated were information sheets presented to volunteers. The level of schooling
of the population that participated in at least one study was determined: 61.7%
of volunteers finished high school and 22.6% had a University degree or diploma;
the remaining 15.7% did not finish high school or the datum was not available.
RESULTS: The results showed that, when the present study began, all information
sheets were "readable" by all volunteers who had at least finished high school.
After these preliminary results, some additional linguistic and graphic
refinements were adopted in drawing up information sheets. Readability improved
to such a degree that all information sheets could be understood by virtually all
volunteers. CONCLUSION: A number of suggestions were identified, which are set
out in this paper to assist in the preparation of improved information sheets and
a recommendation to value the readability of consent sheets before giving them to
the volunteers. The suggestions were split into three categories: communications
to the volunteer, text format and text organisation.
PMID- 11009043
TI - Relative systemic dose potency and tolerability of inhaled formoterol and
salbutamol in healthy subjects and asthmatics.
AB - OBJECTIVES: To compare the relative systemic dose potency and tolerability of
inhaled formoterol and salbutamol and to describe elimination of formoterol,
particularly any enantioselectivity. METHODS: Twelve healthy subjects, aged 18-28
years, completed three open study days, and eleven asthmatic patients, aged 20-56
years, completed four double-blind study days in randomised, placebo-controlled
and crossover fashions. The healthy subjects inhaled 13.5 + 13.5 + 27 microg
formoterol (Oxis) via Turbuhaler and 300 + 300 + 600 microg salbutamol
(Ventoline) via a pressurised metered dose inhaler (pMDI). The asthmatics, being
on formoterol 9 microg twice daily via Turbuhaler during the study, inhaled the
same single doses as the healthy subjects plus 900 + 900 + 1800 microg salbutamol
via pMDI. Doses were given cumulatively 30 min apart on separate study days.
Placebo was a day of no treatment in the healthy subjects. Double dummies were
used for the asthmatics. Cardiovascular and metabolic effects were evaluated.
Elimination of formoterol was addressed in the healthy subjects. RESULTS:
Formoterol was estimated to be 28-109 times as potent as salbutamol, depending on
the systemic effect variable. The duration of systemic action seemed to differ
marginally at approximately equieffective doses of formoterol and salbutamol.
Systemic effects were well tolerated and tended to be more pronounced in the
healthy subjects than in the asthmatic patients. The half-life of the
pharmacologically more active (R;R)-formoterol was longer than that of (S;S)
formoterol. CONCLUSIONS: Systemically, formoterol was shown to be 28-109 times as
potent as salbutamol. Equieffective doses seemed to have a similar duration of
effect. Formoterol and salbutamol were well tolerated by healthy subjects up to
the tested total doses of 54 microg and 1200 microg, respectively, and by
asthmatic patients up to the tested total doses of 54 microg and 3600 microg,
respectively. Elimination of formoterol was enantioselective.
PMID- 11009045
TI - Cardiac effects of co-artemether (artemether/lumefantrine) and mefloquine given
alone or in combination to healthy volunteers.
AB - Co-artemether is an oral tablet of artemether (20 mg) and lumefantrine (120 mg)
for the treatment of falciparum malaria. Administration in the presence of
mefloquine is likely, as co-artemether may be used following failure of
antimalarial prophylaxis or treatment with mefloquine. OBJECTIVE: The effects on
the QTc interval were compared among treatment with three doses of mefloquine
(500, 250, 250 mg over 12 h) followed by six doses of co-artemether (6 x 4
tablets over 60 h) and either treatment alone. The study was performed in a
randomised, double-blind, parallel group design in 14 healthy male subjects per
dose group. METHODS: Electrocardiograms (ECGs) were recorded before dosing and
repeatedly thereafter. The Bazett formula was used to calculate the QTc interval.
The maximum and average QTc intervals for the first, third and sixth dosing
intervals of co-artemether treatment were compared among treatments. Drug plasma
concentrations were determined at identical times with the ECG recordings for
exploratory pharmacokinetic/pharmacodynamic evaluation. RESULTS: No clinically
relevant differences in the QTc interval were observed after sequential
administration of mefloquine and co-artemether relative to either treatment given
alone, and there were no clinically relevant study drug-related effects on the
QTc interval after either treatment. Plasma drug measurements revealed adequate
systemic exposure to artemether, dihydroartemisinin, lumefantrine and mefloquine,
well in line with the clinical setting. No correlation between the length of the
QTc interval and plasma drug concentrations was found for any of the compounds.
CONCLUSIONS: Untoward effects on the QTc interval are unlikely to occur when co
artemether is administered following prophylaxis or treatment with mefloquine.
PMID- 11009046
TI - A comparison of the effects of etodolac and ibuprofen on renal haemodynamics,
tubular function, renin, vasopressin and urinary excretion of albumin and alpha
glutathione-S-transferase in healthy subjects: a placebo-controlled cross-over
study.
AB - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to be
potentially nephrotoxic agents. NSAIDs inhibit the enzyme cyclo-oxygenase and
thereby block the prostaglandin synthesis in the kidneys. Cyclo-oxygenase exists
in two isoforms (COX-1 and COX-2). It has been proposed that NSAIDs with
preferential COX-2 selectivity have fewer renal side effects than drugs with
preferential COX-1 selectivity. Etodolac is a relative selective inhibitor of COX
2, while ibuprofen has a higher potency against COX-1 than COX-2. OBJECTIVE: In
this study, we compared the effects of etodolac and ibuprofen on renal function,
plasma renin, plasma arginine vasopressin and the urinary excretion of albumin
and alpha-glutathione-S-transferase (alpha-GST). METHODS: In a randomised, double
blind, three-way crossover study with placebo, we compared the effects of 2 weeks
of treatment with ibuprofen and etodolac on renal haemodynamics [glomerular
filtration rate (GFR), renal plasma flow (RPF) and filtration fraction (FF)],
tubular function and plasma concentrations of the hormones renin (PRC) and
arginine vasopressin (AVP) in 18 healthy subjects. In addition, we examined the
effects on the urinary excretion of albumin and alpha-GST as markers of renal
injury. RESULTS: No differences were found between the three treatments, placebo,
ibuprofen and etodolac, in the effects on GFR, RPF, FF, free water clearance,
urinary output or fractional excretion of potassium and sodium. However,
ibuprofen, in contrast to etodolac, caused a significant decrease in both lithium
clearance (-16% versus placebo) and the fractional excretion of lithium (-17%
versus placebo), suggesting an increase in the reabsorption in the proximal
tubuli. PRC was reduced significantly by ibuprofen (-32% versus placebo) but not
etodolac. None of the drugs changed AVP. Fourteen days of treatment with
ibuprofen caused a significant decrease (-47% versus placebo) in the urinary
excretion of alpha-GST, while no changes were seen after etodolac. None of the
drugs changed the urinary excretion of albumin. CONCLUSION: In conclusion, a 14
day administration of etodolac or ibuprofen in therapeutic doses did not affect
the renal haemodynamics, the net excretion of electrolytes or the urinary
excretion of albumin in healthy subjects. However, ibuprofen, in contrast to
etodolac, caused a reduction in PRC, suggesting that COX-1 is involved in basal
renin release in humans. Furthermore, ibuprofen decreased lithium excretion
suggesting that COX-1 is involved in the re-absorption of sodium and/or water in
the proximal tubuli. The reduction in the urinary excretion of alpha-GST by
ibuprofen may be caused by an inhibition of the detoxification enzyme by
ibuprofen. Overall the study indicates that only small differences in the effects
of the two drugs on renal function in healthy subjects exist during a treatment
period of 2 weeks.
PMID- 11009047
TI - Concomitant use of mirtazapine and cimetidine: a drug-drug interaction study in
healthy male subjects.
AB - OBJECTIVE: The objective of this study was to examine the pharmacokinetics and
the tolerability/safety of mirtazapine and cimetidine separately and in
combination following oral administration of multiple doses. METHODS: This was a
double-blind, placebo-controlled, two-period cross-over, multiple-dose
pharmacokinetic interaction study in 12 healthy male subjects. They received
either cimetidine (800 mg b.i.d.) or placebo in combination with (commercially
available, racemic) mirtazapine (30 mg nocte). Cimetidine and placebo were
administered for 14 days, with mirtazapine added during days 6-12 of each period.
Serial blood samples for kinetic profiling were taken on day 5 and day 12 for
cimetidine and on days 12-14 for mirtazapine. RESULTS: The co-administration of
cimetidine resulted in a statistically significant increase in the area under the
curve (AUC(0-24)) and Cmax of mirtazapine (54% and 22% respectively). The AUC(0
24) of demethylmirtazapine increased only slightly, and there was no effect on
Cmax. The elimination half-lives for both mirtazapine and its demethyl metabolite
were unaffected by cimetidine co-administration. The trough and average plasma
concentrations during the steady state were elevated during cimetidine treatment
(62% and 54%, respectively). Mirtazapine had no effect on the pharmacokinetics of
cimetidine. CONCLUSION: Co-administration of cimetidine (800 mg b.i.d.) and
mirtazapine (30 mg nocte) resulted in increased steady-state plasma levels of
mirtazapine (C(ss,min) = +61%, P < 0.05; C(ss,av) = +54%, P < 0.05), probably as
a result of increased bio-availability. The Cmax (+22%, P < 0.05) and AUC(0-24)
(+54%, P < 0.05) also increased. Due to the variability of the mirtazapine plasma
levels in patients, the clinical meaning of these increases is probably limited.
Co-administration of mirtazapine did not alter cimetidine pharmacokinetics.
PMID- 11009048
TI - Frequency of cytochrome P450 3A4 variant genotype in transplant population and
lack of association with cyclosporin clearance.
AB - OBJECTIVE: Cytochrome P450 3A4 (CYP3A4) plays a vital role in the oxidative
metabolism of many xenobiotics. Some recent reports have provided circumstantial
evidence in support of an association between a genetic polymorphism (A-->G) in
the 5'-flanking region (-290) of CYP3A4 and altered enzyme activity. We sought to
determine whether genotyping patients for CYP3A4-G could assist with the dose
optimisation of drugs metabolised by this system. METHODS: Normal subjects and
renal-transplant patients receiving cyclosporin for immune modulation were
genotyped for the CYP3A4-G variant. A surrogate for cyclosporin clearance was
estimated from the ratio of the cyclosporin dose, normalised for body weight and
the corresponding trough concentration. The association between genotype and
clearance was examined in patients who received twice-daily doses of cyclosporin
and who were not on concurrent medication known to modify CYP3A4 function.
RESULTS: The allelic frequencies of the CYP3A4-G variant were estimated to be
2.6% and 3% in transplant patients and normal subjects, respectively. The median
cyclosporin pseudo-clearance of transplant patients with wild-type CYP3A4 was
0.90 l/h/kg (range: 0.35-3.8 l/h/kg; n = 86), whereas the corresponding value for
the five patients heterozygotic for the CYP3A4-G variant was 0.71 l/h/kg (range
0.35-0.91 l/h/kg). The distribution of the pseudo-clearance according to genotype
was not found to be significant according to a Fisher's exact test (P = 0.15).
CONCLUSION: Genotyping for the CYP3A4-G polymorphism is unlikely to assist
cyclosporin dose selection in transplant patients.
PMID- 11009049
TI - Pharmacokinetics and pharmacodynamics of a premixed formulation of soluble and
protamine-retarded insulin aspart.
AB - OBJECTIVE: With the aim to obtain a premixed rapid-acting insulin with a serum
insulin profile more closely resembling the endogenous meal-stimulated serum
insulin profiles, a 30/70 (rapid/intermediate-acting) premixed suspension of the
rapid-acting insulin analogue insulin aspart (BIAsp30) was compared with a
similar premixed suspension of biphasic human insulin 30/70 (BHI30) after a
single subcutaneous injection. METHODS: The study had a randomised, double-blind,
two-period crossover design. Twenty-four healthy male subjects received a single
subcutaneous dose of either 0.2 U x kg(-1) bodyweight of BIAsp30 or BHI30 on two
study days. RESULTS: BIAsp30 was absorbed faster than BHI30, as reflected in the
area under the insulin concentration-time curve from 0 to 90 min after dosing
[AUC(0-90 min)]. This was significantly larger for BIAsp30 than for BHI30 (1403
+/- 372 versus 752 +/- 191 mU x l(-1) x min(-1) [mean +/- SD]; P < 0.0001).
Furthermore, the time to maximum serum insulin concentration (tmax) of BIAsp30
was approximately half the tmax of BHI30 (60 [45-70] versus 110 [90-180] min
[median, interquartile range]; P=0.0001) and the maximum insulin concentration
(Cmax) was significantly higher for BIAsp30 than for BHI30 (23.4 +/- 5.3 versus
15.5 +/- 3.7 mU x l(-1) [mean +/- SD]; P < 0.0001). The serum glucose profiles
showed a significantly earlier onset of the glucose-lowering effect following
BIAsp30 than following BHI30. CONCLUSIONS: The improved absorption properties of
soluble insulin aspart in its premixed formulation provide a basis for a more
efficient meal-related glucose control and immediate pre-meal delivery when
compared with a similar human premixed insulin in the treatment of diabetes
mellitus.
PMID- 11009050
TI - Metabolism of chloramphenicol succinate in human bone marrow.
AB - OBJECTIVE/METHODS: The metabolism of chloramphenicol succinate (CAPS) by human
bone marrow was studied in vitro using 75 marrow samples. Whole marrow samples
were incubated with CAPS with or without reduced nicotinamide adenine
dinucleotide phosphate for 1, 2 and 3 h at 37 degrees C. Ficoll-paque-separated
marrow mononuclear cells and erythrocytes were similarly incubated. After
precipitation and centrifugation, clear supernatant was analysed for the presence
of metabolites using high-performance liquid chromatography. RESULTS: Only one
metabolite was detected when CAPS was incubated for 3 h with whole marrow from 72
donors. Its retention time (RT 10.9 min) corresponded to chloramphenicol (CAP).
When CAPS was incubated with samples of whole marrow, marrow mononuclear cells,
marrow erythrocytes, marrow plasma and peripheral blood from one donor who had
taken Traditional Chinese Medicine (TCM), three metabolite peaks were detected
within 15 min to 1 h. The RT of two of these peaks corresponded to CAP and
nitroso-CAP (RT 14.9 min), but one peak remained unidentified. These peaks were
not detected in the control samples incubated without CAPS. Blood samples
collected after 3 months and 6 months to reconfirm metabolic activity yielded no
such metabolite peaks when incubated with CAPS for 1-3 h. Therefore induction of
enzyme activity by TCM was suspected. Three metabolite peaks with the same RTs
were also detected when CAPS was incubated for 3 h with whole marrow from two
other donors. CONCLUSION: These studies demonstrated that CAPS may be metabolised
to CAP and occasionally other metabolites in human bone marrow. This novel
observation is particularly important because the bone marrow is known to be a
target organ for chloramphenicol toxicity.
PMID- 11009051
TI - Effect of grapefruit juice dose on grapefruit juice-triazolam interaction:
repeated consumption prolongs triazolam half-life.
AB - OBJECTIVE: Grapefruit juice inhibits CYP3A4-mediated metabolism of several drugs
during first pass. In this study, the effect of grapefruit juice dose on the
extent of grapefruit juice-triazolam interaction was investigated. METHODS: In a
randomised, four-phase, crossover study, 12 healthy volunteers received 0.25 mg
triazolam with water, with 200 ml normal-strength or double-strength grapefruit
juice or, on the third day of multiple-dose [three times daily (t.i.d.)]
administration of double-strength grapefruit juice. Timed blood samples were
collected up to 23 h after dosing, and the effects of triazolam were measured
with four psychomotor tests up to 10 h after dosing. RESULTS: The area under the
plasma triazolam concentration time curve (AUC(0-infinity)) was increased by 53%
(P < 0.01), 49% (P < 0.01) and 143% (P < 0.001) by a single dose of normal
strength, a single dose of double-strength and multiple-dose administration of
double-strength grapefruit juice, respectively. The peak plasma concentration
(Cmax) of triazolam was increased by about 40% by a single dose of normal
strength grapefruit juice (P < 0.01) and multiple-dose grapefruit juice (P <
0.01) and by 25% by a single dose of double-strength grapefruit juice (P < 0.05).
The elimination half-life (t(1/2)) of triazolam was prolonged by 54% during the
multiple-dose grapefruit juice phase (P < 0.001). A significant increase in the
pharmacodynamic effects of triazolam was seen during the multiple-dose grapefruit
juice phase in the digit symbol substitution test (DSST, P < 0.05), in subjective
overall drug effect (P < 0.05) and in subjective drowsiness (P < 0.05).
CONCLUSIONS: Even one glass of grapefruit juice increases plasma triazolam
concentrations, but repeated consumption of grapefruit juice produces a
significantly greater increase in triazolam concentrations than one glass of
juice. The t(1/2) of triazolam is prolonged by repeated consumption of grapefruit
juice, probably due to inhibition of hepatic CYP3A4 activity.
PMID- 11009052
TI - Pattern of antibiotic use in primary health care in Italy.
AB - OBJECTIVE: The overuse and misuse of antibiotics have been related to the growing
emergence of bacterial resistance. The aim of the present study was to assess the
pattern of antibiotic use by Italian general practitioners (GPs) in the treatment
of the most frequent infectious problems. METHODS: The study was performed with
131 GPs recruited on a voluntary basis from among the 181 GPs contacted in two
Italian regions, Emilia Romagna and Umbria. GPs were requested to report all the
infectious events encountered during six sample weeks on a special form, whether
an antibiotic was administered or not. RESULTS: The GPs reported 7095 infectious
cases, of which 5036 (77%) were respiratory-tract infections (RTIs) and 749 (11%)
were urinary-tract infections (UTIs). Antibiotics were prescribed in 71% of the
cases. The proportion of antibiotic-treated cases was highest in UTIs (97%),
followed by lower respiratory-tract infections (LRTIs; 93%) and upper respiratory
tract infections (URTIs; 54%). Drugs belonging to 16 Anatomical Therapeutical
Chemical groups (fourth level) were used. Wide-spectrum penicillins and
macrolides ranked first (23%), followed by penicillins plus beta-lactamase
inhibitors (15%), cephalosporins (15%) and fluoroquinolones (10%). The most
prescribed antibiotics for the major disease groups were wide-spectrum
penicillins for URTIs (36%), macrolides and cephalosporins for LRTIs (27% each)
and fluoroquinolones for UTIs (46%). CONCLUSIONS: The present survey showed a
high level of inappropriate use. In fact, a large number of infectious diseases,
including infections commonly caused by viral agents, were treated with an anti
bacterial drug. Italian GPs had a tendency to preferentially prescribe wide
spectrum antibiotics and to use, in many cases, antibiotics that are rarely of
choice in primary health care, such as cephalosporins and fluoroquinolones. In
order to attain a more evidence-based prescription, local guidelines shared by
specialists and GPs should be implemented.
PMID- 11009053
TI - Incidence of lethal adverse drug reactions in the comprehensive hospital drug
monitoring, a 20-year survey, 1974-1993, based on the data of Berne/St. Gallen.
AB - OBJECTIVES: Realising the limitations of spontaneous drug monitoring systems
concerning the epidemiological aspects, a comprehensive program was founded. It
was based on previous publications from the US, Canada and Northern Ireland,
mainly those of the BCDSP (Boston Collaborative Drug Surveillance Programme).
METHODS: Drug monitoring was carried out by a group of physicians which included
the medical head of each of the divisions of internal medicine, a statistician
and an informatician. Only probable or definite drug event relationships were
included. A probable event is defined as one in which the drug interaction was
more likely to be the cause than any non-drug-related cause. The same criteria
were valid for the lethal reactions. RESULTS: In the present evaluation, we found
26 probable lethal adverse drug reactions out of a total of 48,005 patients
consecutively admitted to the divisions of internal medicine of three Swiss
teaching hospitals during the years 1974-1993, an incidence of 0.054%. The median
age of the cohort was 68 years (range 11-103 years), of which 49% were women. The
median hospital stay was 14 days and the median number of drugs was eight per
patient. CONCLUSION: The patients with a lethal outcome were presented under the
eight pharmacologic-therapeutic classes of drugs and the classification proposed
by NS Irey. This is based on long histopathologic experience and helps to
identify preventable risks.
PMID- 11009054
TI - Differences in the potencies of inhaled steroids are not reflected in the doses
prescribed in primary care in New Zealand.
AB - OBJECTIVE: To determine whether the average doses of inhaled beclomethasone,
fluticasone and budesonide prescribed in primary care reflect the relative
potencies of these medicines. METHODS: Retrospective analysis of 95,540
prescriptions for inhaled steroids written by 293 general practitioners in
Auckland, New Zealand, between November 1995 and June 1998. In addition, 177
general practitioners were presented with two case histories describing patients
with uncontrolled asthma who were not on treatment with inhaled steroids. They
were asked which medicine they would prescribe and in what dose. RESULTS: The
average daily doses prescribed were 600 microg for fluticasone, 747 microg for
beclomethasone and 1184 microg for budesonide. The average dose of fluticasone
was 80% of that for beclomethasone. In May 1997, when 4.5% of the prescriptions
for inhaled steroids were for fluticasone, the average doses of fluticasone and
beclomethasone were 632 microg and 760 microg, respectively. By May 1998, when
23% of prescriptions were for fluticasone, the average doses of fluticasone and
beclomethasone were little changed at 610 microg and 726 microg, respectively. In
response to the two case histories, the average doses of fluticasone chosen were
71% and 77% of the doses of beclomethasone. CONCLUSIONS: The average prescribed
dose of fluticasone was 80% of that for beclomethasone, even though fluticasone
is at least twice as potent as beclomethasone. Similar findings were observed
when the general practitioners responded to the case histories. The high doses of
fluticasone prescribed may be due to a failure to appreciate that fluticasone is
twice as potent as beclomethasone and to the availability of high strength
preparations of fluticasone, i.e. 250 microg per actuation.
PMID- 11009055
TI - Do alcoholic beverages enhance availability of ivermectin?
PMID- 11009056
TI - The effect of pantoprazole on tacrolimus and cyclosporin A blood concentration in
transplant recipients.
PMID- 11009057
TI - Policing the European pharmaceutical market's priorities.
PMID- 11009058
TI - Effects of ethnicity on skeletal maturation: consequences for forensic age
estimations.
AB - An X-ray of the hand is an important method in forensic science for estimation of
the age of juvenile suspects with uncertain date of birth. Relevant X-ray
standards for evaluation of skeletal maturity are available for white US
Americans as well as for North and Central Europeans. The applicability of these
standards to members of ethnic groups different from the reference population has
been the subject of controversial discussion. More than 80 publications were
analysed with the view to finding out whether skeletal maturation is affected by
ethnic identity. It was concluded that skeletal maturation takes place in phases
which are identically defined for all ethnic groups. Time-related differences in
passing those stages of skeletal maturation within the relevant age group appear
to be unaffected by ethnic identity. It is the socioeconomic status of a given
population which is of decisive importance to the rate of ossification. The
application of X-ray standards to individuals of a socio-economic status lower
than that of the reference population usually leads to underestimation of that
person's age. In terms of criminal responsibility, this is of no adverse effect
on the person concerned.
PMID- 11009059
TI - Suicides by sharp force: typical and atypical features.
AB - A total of 65 consecutive cases of suicide by sharp force were investigated by
evaluating the autopsy and prosecution department records. Suicides constituted
17% of all fatalities from sharp force autopsied between 1967 and 1996. Young
males and persons with a psychiatric history predominated among the persons who
chose this "hard" method of suicide. The most common implements used were knives
(62%) and razor blades (15%). Cutting injuries in isolation were present in 26,
stab injuries in isolation in 24 and a combination of both in 15 fatalities. The
number of injuries per case varied from 1 to 37 but 1/3 showed one injury. More
than 85% of the cutting injuries were located at the wrist, elbow crease or neck
whereas 79% of the stab injuries involved the ventral aspect of the trunk.
Perforation of clothing was present in 16 (52%) out of 31 stab injuries to the
trunk. Injuries to more than one body region were observed in 34 (52%) cases.
Tentative marks were present in 50 (77%) fatalities and the number varied from 1
to 60 per case. Superficial incisions of the fingers were found in 15% with razor
blades constituting the weapon in half of these cases. Deviations from these
typical patterns occurred not infrequently. The utter determination of the victim
to carry it through or the use of unusual weapons resulted in a few bizarre cases
which are outlined briefly.
PMID- 11009060
TI - Genetic variability at nine STR loci in the Chueta (Majorcan Jews) and the
Balearic populations investigated by a single multiplex reaction.
AB - A study of the genetic variability in the Chueta (Majorcan Jews) and the Balearic
(Majorca and Minorca Islands) populations was carried out using a multiplex
system containing the nine tetrameric STRs D3S1358, vWA, FGA, D8S1179, D21S11,
D18S51, D5S818, D13S317 and D7S820. The Chueta population has remained isolated
because intermarriage with non-Jews did not take place until the middle of this
century, which has resulted in it being a small inbred community. The results
indicate the existence of HW equilibrium for the Chueta and Balearic populations.
No pair-wise correlation was observed between the nine markers. Consequently,
they seem to comprise a suitable group of markers for population genetics
purposes and for paternity and forensic testing.
PMID- 11009062
TI - Analysis of eight STR loci in two Hungarian populations.
AB - A multiplex reaction for the eight STR loci D3S1358, FGA, D8S1179, D21S11,
D18S51, D5S818, D13S317, D7S820 was used to generate allele frequency databases
for two Hungarian population samples, Caucasians from the Budapest area and
Romanies from Baranya county. During the analysis two intermediate-sized alleles
and a sequence variant allele were observed at the D7S820 locus. All three types
of allelic variants were found to have modifications in the same block of a (T)9
stretch located within the 3' flanking region of each allele, which may indicate
a possible higher mutation rate of this (T)9 block. For the loci D3S 1358 and
D7S820 the Romany population database showed departures from Hardy-Weinberg
equilibrium. The forensic efficiency values for the Romany population were
slightly different from those found in the Hungarian Caucasian population.
Comparing the allele frequency values by G-statistic, calculating the F(ST)
indices and with the pair-wise comparisons of interpopulation variance, the two
Hungarian populations could be distinguished using data from the eight STR loci.
PMID- 11009061
TI - Immunohistochemical investigation of a pulmonary surfactant in fatal mechanical
asphyxia.
AB - We evaluated the usefulness of pulmonary surfactant protein A (SP-A) as a
practical diagnostic marker of fatal mechanical asphyxia in forensic autopsy
cases. A total of 27 cases of asphyxia were examined histologically and
immunohistochemically and compared with a control group consisting of 16 cases of
poisoning (n = 9) and peracute death (n = 7). Both groups showed histological
findings of local atelectasis and local emphysema, congestion, intra-alveolar and
interstitial edema in most cases and pulmonary hemorrhages in some cases. The
mechanical asphyxia group showed a significantly increased intensity of SP-A
staining in the intra-alveolar space accompanied by many massive aggregates in
approximately 60% of cases, which was not found in the control group. These
structures may be interpreted as aggregates of pulmonary surfactant released from
the alveolar wall due to enhanced secretion caused by strong forced breathing or
over-excitement of the autonomic nervous system by mechanical asphyxia. The
results of our investigation suggest the practical usefulness of the
immunohistochemical detection of SP-A in distinguishing mechanical asphyxia from
other types of hypoxia.
PMID- 11009063
TI - Myocardial findings in fatal carbon monoxide poisoning: a human and experimental
morphometric study.
AB - The aim of this study was to define the status of the myocardium in selected
human cases of acute, fatal carbon monoxide intoxication and the myocardial
changes in rats exposed to carbon monoxide in relation to the type of cardiac
arrest and the effects of reoxygenation following pre-fatal CO intoxication. The
human study consisted of 26 cases (17 accidental and 9 suicide) of acute, fatal
CO intoxication, without evidence of obstructive coronary atherosclerosis or
history of ischemic heart disease which were compared with 45 cases of fatal head
trauma in subjects who died instantaneously (26 cases) or within 1-12 h (19
cases). Inhalation of a lethal dose of CO in rats was compared with sub-lethal
doses plus reoxygenation with and without pre-treatment by a betablocker. In all
human and experimental histological sections, changes were normalised per mm2
area. In the human cases the myocardium did not show any ischemic types of
changes or other lesions. Only in "three accidental" cases a few, small foci of
coagulative myocytolysis were detected. In the case of spontaneous death in 31
rats following CO intoxication, no pathological myocardial changes were seen. Of
the 15 "reoxygenated" rats, 2 of the 7 spontaneous deaths presented coagulative
myocytolysis with 15 +/- 6 foci and 381 +/- 255 necrotic myocells. All the eight
rats sacrificed at 3 h had coagulative myocytolysis with 5 +/- 4 foci and 60 +/-
47 myocells. Of the 24 reoxygenated rats pre-treated with a betablocker, 5 died
spontaneously after a short survival and 2 of these showed 11 +/- 9 foci and 21
+/- 20 myocells. The 19 rats sacrificed after 3 h all presented coagulative
myocytolysis with figures of 75 +/- 43 and 356 +/- 301 with 0.5 mg/kg of
propranolol hydrochloride and 55 +/- 45 and 253 +/- 216 with 2 mg/kg,
respectively.
PMID- 11009064
TI - Pressure sores: epidemiology, medico-legal implications and forensic
argumentation concerning causality.
AB - The aim of the present investigation was to identify the frequency and grading of
pressure sores in a large series of unselected consecutive deceased subjects
before cremation and to discuss aspects of the forensic argumentation concerning
causality. A total of 10,222 corpses were examined prospectively over a 1-year
period (1998) for the occurrence, localization and grading of pressure sores.
Epidemiological aspects (e.g. age, sex, underlying and contributing causes of
death, place of death etc.) were taken from the death certificate. The mean
prevalence of pressure sores was 11.2% (87.1% isolated sores; predominant
localization of advanced grades on the sacrum in 69.6%). There was a positive
correlation between the prevalence of sores and advanced age resulting in a clear
female predominance in the age group of 80 years and over because of differences
in life expectancy. A significant correlation was found between the prevalence of
pressure sores and certain underlying diseases, e.g. trauma, senile dementia,
neurological diseases, apoplexy and marasmus. Pressure sores of all grades were
more frequently found in the deceased when a senior citizen's or nursing home was
given on the death certificate as the domicile in the last period of life. The
forensic argumentation for the causal relationship of a pressure sore as the
focus of fatal infectious complications or septicemia has to be based on the
results of clinical expertises and forensic investigations (evaluation of the
institutional documentation of the patient's course, autopsy findings, histology,
immunohistochemistry). The vast majority of physicians seem to pay only little
attention to the potentially fatal outcome of pressure sores and fatalities
associated with this condition are clearly underreported. From the point of view
of social medicine, the prevalence of pressure sores in a defined population can
be seen as a parameter for the quality of nursing and medical care. In bringing
these fatalities to light, the field of legal medicine contributes to a general
quality control of standards of nursing and medical care.
PMID- 11009065
TI - The time course of the vascular response to human brain injury--an
immunohistochemical study.
AB - In a total of 104 individuals who had sustained traumatic brain injury (TBI), the
time-dependent vascular response was investigated at the injured cortical area
during the first 30 weeks after the trauma. The immunohistochemical staining of
the cerebral blood vessels was performed with antibodies against laminin, type IV
collagen, tenascin, thrombomodulin and factor VIII associated antigen. Compared
to the immunoreactivity in unaltered control tissue, a significantly increased
vascular expression could be detected in cortical contusions after a
postinfliction interval of at least 3 h for factor VIII, after 1.6 days for
tenascin or after 6.8 days for thrombomodulin, whereas the immunostaining for
laminin and type IV collagen was regularly positive even in the vascular
endothelium of uninjured brain tissue.
PMID- 11009067
TI - Polymarker, HLA-DQA1 and D1S80 allele data in a Zimbabwean Black sample
population.
AB - Allele frequencies for the seven PCR-based loci (LDLR, GYPA, HBGG, D7S8, Gc, HLA
DQAI, and D1S80) were determined in a Black African population from Zimbabwe. All
loci are highly polymorphic and meet Hardy-Weinberg expectations. An interclass
correlation analysis detected only two significant departures from independence
out of 21 pair-wise comparisons of the 7 loci. The Black African allele frequency
data are similar to African American data at four of the seven PCR-based loci.
PMID- 11009066
TI - ROC analysis of alcoholism markers--100% specificity.
AB - A combination of 4 so-called markers of alcoholism, i.e. methanol, acetone + 2
propanol, gamma-glutamyltransferase and carbohydrate deficient transferrin, was
investigated in 341 blood samples from alcoholics and non-alcoholics. From the
history of alcohol consumption, four defined subgroups were formed: non
alcoholics divided into (A) 33 persons with no ethanol consumption during the
past year and (B) 60 persons with daily consumption less than 40 g ethanol.
Alcoholics were divided into (C) 177 persons with no ethanol at the time of
admission/first blood sampling (withdrawal therapy) and (D) 71 persons with
positive ethanol levels on admission/first blood sampling. All markers showed
different extents of overlap between the collectives of alcoholics and non
alcoholics. By logistic regression, a formula was developed combining these
markers with different mathematical weights. Thus an "Alc-Index" could be
calculated for each individual. The ROC curve connecting all individual values
gives an ideal form with 100% specificity and nearly 93% sensitivity. The
threshold between the collectives of alcoholics and non-alcoholics was defined by
the Alc-Index value 1.7. This was associated with no false positives among the
non-alcoholics while nearly 93% of the alcoholics exceeded this index. The ROC
based calculation of the Alc-Index thus seems to be the most effective method for
the diagnosis of alcoholism.
PMID- 11009069
TI - Frontal lobe membrane phospholipid metabolism and ventricle to brain ratio in
schizophrenia: preliminary 31P-MRS and CT studies.
AB - A number of studies employing in vivo phosphorous-31 magnetic resonance
spectroscopy (31P-MRS) have demonstrated altered measurements of frontal
phospholipid and high energy phosphorus metabolism in schizophrenia. Enlargement
of both the cerebroventricular system and the cortical sulci also has been
reported as the most consistent pathological finding in schizophrenia by several
investigators. To our knowledge, however, only two studies have simultaneously
examined structural and functional aspects of the biological substrate of
schizophrenia in the same patients. Moreover, they may have failed to find a
significant correlation between these variables because of small sample sizes.
The possible relationship between frontal lobe membrane phospholipid metabolism
and ventricle-to-brain ratio (VBR) in patients with schizophrenia was
investigated. In 31 schizophrenic patients, frontal lobe membrane phospholipid
metabolism was measured by 31P-MRS, and VBR was measured by computed tomography
(CT). Stepwise multiple regression analysis disclosed that VBR positively
correlated only with increased phosphodiester (PDE) level (beta = 0.381, p =
0.0345), but with no other metabolites. This finding may provide evidence for an
association between structural brain abnormality and altered frontal lobe
membrane metabolism in schizophrenic patients, although the p-value of the
finding is not high.
PMID- 11009068
TI - hKCNN3 which maps to chromosome 1q21 is not the causative gene in periodic
catatonia, a familial subtype of schizophrenia.
AB - The human calcium-activated potassium channel gene (hKCNN3, hSKCa3) contains two
tandemly arranged, multiallelic CAG repeats located in exon 1 which result in
short to moderate polyglutamine stretches of unknown functional significance.
Case-control and family-based association studies suggested an association of
hKCNN3 repeats with susceptibility for schizophrenia. Twelve multiplex pedigrees
with periodic catatonia, a schizophrenia subtype with major gene effect and
patterns of anticipation, were genotyped using the multiallelic hKCNN3 repeat
polymorphism. Using a dominant model of inheritance with sex- and age-dependent
penetrance classes, cumulative results showed exclusion of linkage of hKCNN3 to
periodic catatonia under the assumption of genetic homogeneity with lod score of
48.01 at zero recombination fraction. Our results provide evidence that hKCNN3 is
not the causative gene in the familial schizophrenia subtype of periodic
catatonia. By fluorescent in situ hybridization we confirmed the assignment of
hKCNN3 to chromosome 1q21 near the heterochromatin region. Linkage mapping showed
segregation with marker D1S498 (theta = 0.05) and placed hKCNN3 in the genetic
linkage map in a cluster of genes near the centromeric region of chromosome 1.
PMID- 11009070
TI - Comparing self- and expert rating: a self-report screening version (SIAB-S) of
the structured interview for anorexic and bulimic syndromes for DSM-IV and ICD-10
(SIAB-EX).
AB - OBJECTIVE: Carrying out structured interviews in larger numbers by well-trained
interviewers is costly and time consuming. Therefore, we developed parallel to
the existing Structured Interview for Anorexic and Bulimic Syndromes (SIAB-EX) a
similarily designed questionnaire for symptoms of disordered eating and related
areas (SIAB-S). METHOD: 377 treated eating disordered patients were assessed
within a two-week time period using both the SIAB-EX and SIAB-S. RESULTS:
Generally, self-ratings based on the SIAB-S were quite similar to expert ratings.
Cohen's kappa showed good agreement between self- and expert ratings. Factor
structure based on principal component analyses of expert ratings or self-ratings
led to rather similar results confirming the robustness of the subscales in self-
and expert ratings. Using expert rating as a criterion, the self-rating (SIAB-S)-
which can more easily be used for screening purposes--had a sensitivity of 0.70,
a specificity of 0.80 and a PPV = 0.91 for the DSM-IV diagnoses of AN and/or BN
(worst ever condition). Diagnostic sensitivity (79/73%) and specificity (66/63 %)
were in an acceptable range (past/current). If we focus on the differences
between the two approaches the following was found: self-rating (compared to
expert-rating) resulted in lower scores for items inquiring about binges and
inappropriate compensatory behaviour, attitudes towards food and eating, and
social interaction. On the other hand, self-rating (compared to expert-rating)
led to higher scores for items measuring general psychopathology and atypical
binging. CONCLUSION: Compared to the "gold standard" of t data obtained with
investigator-based standardised or structured interviews, data based on self
rating with items formulated clearly and concisely can lead to reliable and valid
results. While complex issues (what is a binge) are difficult to assess in self
ratings, some (very personal) questions may even be better asked in a self-report
questionnaire.
PMID- 11009071
TI - Comorbidity of mild cognitive disorder and depression--a neuropsychological
analysis.
AB - Mild cognitive impairment is found in many cases of depression, and it is mostly
assumed to improve during the time course of depression remission. Recent data
question the reversibility of low cognitive test performance in depression. The
aim of this study is to determine the degree of reversibility and the proportion
of patients who will not demonstrate reversibility of cognitive dysfunction.
Consecutive inpatients suffering from depression (N=102) were investigated and
N=82 matched control subjects. N=57 of the patients were diagnosed as major
depression according to DSM-IV. A total of N=67 could be retested after remission
of depression (N=32 of the patients with major depression) and a matched control
group (N=62). Neuropsychological tests were applied in a test session which
avoids the effects of fatigue in the patients by the short duration of strenuous
tests. For most neuropsychological tests an impaired performance in the depressed
patients was found. About one third of the depression subjects performed at an
impaired level in tests of averbal memory and verbal fluency (below 5th
percentile). In the follow-up investigation, a slight improvement in performance
could be assessed for both the depression and the control group, which was,
however, attributed to a general test training effect. No normalization of
cognitive test performance was found in spite of complete recovery of the
affective symptoms. No correlation between the duration of the disease before the
index episode or number of episodes and cognitive deficits could be found. The
data of the neuropsychological deficits of depressed patients, which are stable
in the time course of the affective disorder, may indicate that these patients
may suffer from comorbidity of both depression and mild cognitive disorder. The
findings are discussed as 1) indicating only a minor impact of the depressed mood
on the cognitive performance and 2) they are consistent with a role of brain
lesions which have been reported in several studies in a subgroup of depression.
PMID- 11009072
TI - Naturally occurring benzodiazepines: current status of research and clinical
implications.
AB - Naturally occurring benzodiazepines (BZDs) were first detected in mammalian
tissues in 1986. They comprise a variety of 1,4-benzodiazepines corresponding to
drugs commercially available for the treatment of anxiety disorders, sleep
disturbances and epileptic seizures. Several biosynthetic pathways leading to the
formation of BZDs are currently being discussed and have led to the proposition
of possible precursor molecules. For years, the identification of naturally
occurring BZDs in mammalian organisms was mostly confined to post mortem CNS
material for sensitivity reasons. While radioimmunoassay and radioreceptor assay
techniques have been tentatively applied to quantitations of genuine BZDs from
human milk and cerebrospinal fluid, accurate measurements in peripheral blood
have only recently become accessible, e. g., by gas chromatography/selected ion
monitoring-mass spectrometry (GC/SIM-MS). This review summarizes existing
evidence of benzodiazepines' occurrence in nature and discusses implications for
neuropsychiatric disorders.
PMID- 11009073
TI - Dopamine D4 receptor gene polymorphism and personality traits in healthy
volunteers.
AB - An association between long alleles of a variable number tandem repeat (VNTR)
polymorphism in the dopamine receptor D4 gene and the extraversion related
personality traits Excitement and Novelty Seeking has been reported in healthy
subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian
volunteers were analysed for a potential relationship between the dopamine
receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the
Revised Neo Personality Inventory (NEO PI-R). The present study did not yield
evidence for an association between Extraversion and the dopamine receptor D4
polymorphism.
PMID- 11009074
TI - Frontal dysfunction in schizophrenia--a new electrophysiological classifier for
research and clinical applications.
AB - We determined whether schizophrenic patients can be reliably classified with
electrophysiological tools. We developed a fully computerized classifier based on
5 minutes of EEG recording during an acoustical choice reaction time task (AMDP
module IV). We included factorized variables from the frequency domain and evoked
potentials (N100/P200-complex) from central and frontal electrodes, which were
preprocessed in a sample of 150 normal subjects prior to classification. We
applied discriminant analyses to the electrophysiological data from depressive,
schizophrenic and schizotypal subjects, most of them being unmedicated or drug
naive. The classifier was developed on a training set (33 schizophrenics, 49
normals) and tested on an independent sample (32 schizophrenics, 49 normals). A
simple three-variable classifier was found to classify schizophrenics and normals
in 77% of those tested correctly. Diagnostic specificity of the classifier proved
to be low as the inclusion of depressive patients (n= 60) significantly decreased
classification power. It was demonstrated that atypical but not typical
neuroleptic drugs may influence the classification results. Correctly classified
schizophrenics showed significantly more negative symptoms and slower reaction
times than those schizophrenics who were misclassified as normals. In contrast,
these misclassified schizophrenics showed a non-significant trend for more
positive symptoms and shorter reaction times. As the correctly classified
schizophrenics showed increased frontally pronounced delta-activity and decreased
signal power of the N100/P200 amplitude, it was concluded that these
schizophrenics show dysfunction of the frontal lobe. It is proposed that this new
classifier can be useful for clinical and research applications when subtyping of
schizophrenics with detection of frontal dysfunction as the aim.
PMID- 11009075
TI - Mitogen-activated kinase kinase kinase 1 regulates T cell receptor- and CD28
mediated signaling events which lead to NF-kappaB activation.
AB - Optimal activation of Rel/NF-kappaB transcription factors in T lymphocytes
requires a CD28-delivered co-stimulatory signal in addition to TCR engagement.
Although, Rel/NF-kappaB transcription factors are critical regulators of many T
cell functions, the mechanisms and molecules, which link the surface receptors to
their activation, are poorly characterized. Using Jurkat T cells stimulated with
superantigen presented on B7-positive APC, we showed that CD28- and TCR
stimulated NF-kappaB-dependent transcription is associated to the activation of
IkappaB kinase beta (IKKbeta) and, to a lesser extent, of IkappaB kinase alpha
(IKKalpha). A dominant negative mutant of the MAP3 kinase MEKK1, a kinase known
to regulate the JNK pathway and to activate NF-kappaB-dependent transcription in
many cell types, strongly inhibits CD28- and TCR-induced IKK activity, whereas
the dominant negative mutants of the NF-kappaB-inducing kinase (NIK) did not
exert any significant effects. In addition, TCR/CD28 stimulation results in the
recruitment and autophosphorylation of endogenous MEKK1, whereas endogenous NIK
was not detectably activated. Our data identify MEKK1 as a critical step in
coupling signals initiated by TCR and CD28 to the downstream pathways which lead
to both AP-1 and NF-kappaB activation in T lymphocytes.
PMID- 11009076
TI - CD4+ T cells contain Mycobacterium tuberculosis infection in the absence of CD8+
T cells in mice vaccinated with DNA encoding Ag85A.
AB - The contribution of CD8+ and CD4+ T cell-mediated effector functions against
Mycobacterium tuberculosis infection elicited by i.m. vaccination with plasmid
DNA encoding the immunodominant Ag85A antigen of M. tuberculosis was studied.
Ag85A DNA-vaccinated beta2-microglobulin gene-deficient (beta2m-/-) mice, which
lack CD8+ T cells, produced Ag85-specific antibodies and Th1 type cytokines
similar to wild-type mice. Although beta2m-/- mice were more susceptible to M.
tuberculosis infection, following vaccination they efficiently controlled
bacterial replication in spleen and lungs 4 weeks post-infection. In contrast,
mice lacking CD4+ T cells were neither sensitized by the Ag85A DNA vaccine to
produce Ag85-specific antibodies or Th1 type cytokines nor did they contain a M.
tuberculosis challenge infection. In addition, Ag85A DNA-vaccinated IFN-gamma
gene knockout mice produced Ag85-specific antibodies and IL-2 but died rapidly
following a M. tuberculosis challenge infection. Collectively, these data support
the view that IFN-gamma-producing CD4+ T cells, independently of CD8+ T cells,
may mediate the protective effect of the Ag85A DNA vaccine.
PMID- 11009077
TI - Anti-TCR Vbeta-specific DNA vaccination prolongs heart allograft survival in
adult rats.
AB - Allospecific T cells are known to play a central role in the process of allograft
rejection. Recently, it has been shown that T cell function could be specifically
targeted using DNA vaccination. In our model, PCR analysis of the TCR-beta chain
repertoire of T cells infiltrating rejected allografts showed specific expansions
of the Vbeta13 and Vbeta2 families. In this study, we tested the effect on
allograft survival of DNA vaccination against a specific TCR Vbeta, in a model of
heart allograft rejection in adult rats. Our results showed that anti-TCR Vbeta13
DNA vaccination lead to a significant prolongation of allograft survival compared
to vaccination against other Vbeta families or untreated recipients. The
prolongation of allograft survival correlated in vitro with a decrease in anti
donor reactivity of spleen cells from Vbeta13-vaccinated rats. These results show
that, in a transplantation model, DNA vaccination could be used as a method to
specifically manipulate a T cell response and thus prolong allograft survival.
PMID- 11009078
TI - c-Myc inhibits CD11a and CD11c leukocyte integrin promoters.
AB - The c-Myc transcription factor is an important regulator of cell growth and
differentiation, and its gene repression ability seems to play a key role in Myc
mediated cellular transformation. Since Myc overexpression has been associated
with reduced expression of beta1 and beta2 integrins, we have investigated the
role of c-Myc on CD11a and CD11c transcription. c-Myc inhibited CD11a and CD11c
integrin promoter activity in co-transfection experiments, and similar repression
was obtained in cells where c-Myc expression (KmycB) or activity (Rat-1 c-MycER)
is inducible. The c-Myc repression on the CD11c promoter was independent of the
USF-binding site (USF-150), other putative Myc-binding elements, or the integrity
of the initiator (Inr)-like sequence present at the major transcriptional start
site. Analysis of deletion and mutant promoter constructs revealed that, in the
absence of additional upstream cisacting elements, an AP-1-binding site at -60
(AP1-60) is required for c-Myc repressor activity. The c-Myc repressor activity
on both integrin promoters was abrogated by deletion of c-Myc residues 106-143, a
domain involved in Inr-dependent transcriptional repression. These results
demonstrate a direct effect of c-Myc on integrin gene transcription and suggest
the existence of a c-Myc-dependent mechanism for coupling leukocyte integrin
expression to the cell proliferative state.
PMID- 11009079
TI - Developmental regulation of TCR efficiency.
AB - Unresponsiveness of mature T cells to the same self-peptide/self-MHC molecule
complexes with which thymocytes have reacted during positive selection results
from an increase of activation thresholds during maturation. The molecular events
accounting for this increase are still unknown. In mature cells, a strong
correlation between the extent of TCR down-modulation and T cell responses has
been demonstrated. Exploiting this relationship, we show that the efficiency with
which the TCR mediates full signaling is developmentally regulated. It decreases
with thymic maturation and then increases with differentiation of naive T cells
into memory lymphocytes. This analysis based on TCR modulation revealed an
unexpected characteristic of the T cell receptor: its ability to signal fully is
regulated inversely by its level of expression. This latter relationship may
apply to other receptors both within and outside the immune system.
PMID- 11009080
TI - CD8+ T lymphocyte responses are induced during acute hepatitis C virus infection
but are not sustained.
AB - Cellular immune responses are likely to play a key role in determining the
clinical outcome in acute infection with hepatitis C virus (HCV), but the
dynamics of such responses and their relationship to viral clearance are poorly
understood. In a previous study we have shown highly activated, multispecific
cytotoxic T lymphocyte responses arising early and persisting in an individual
who subsequently cleared the virus. In this study the HCV-specific CD8+
lymphocytes response has been similarly analyzed, using peptide-HLA class I
tetramers, in a further nine individuals with documented acute HCV infection, six
of whom failed to clear the virus. Significant populations of virus-specific CD8+
lymphocytes were detected at the peak of acute hepatic illness (maximally 3.5% of
CD8+ lymphocytes). Frequencies were commonly lower than those seen previously and
were generally not sustained. Early HCV-specific CD8+ lymphocytes showed an
activated phenotype in all patients (CD38+ and HLA class II+), but this
activation was short-lived. Failure to sustain sufficient numbers of activated
virus-specific CD8+ lymphocytes may contribute to persistence of HCV.
PMID- 11009081
TI - Differential regulation of Ly49 expression on CD4+ and CD4-CD8- (double negative)
NK1.1+ T cells.
AB - The pan-NK cell marker NK1.1, present in some mouse strains, is also found on a
subset of TCRalphabeta+ lymphocytes termed NKT cells. These cells are primarily
CD4+ or CD4-CD8- (double negative, DN), and both NKT subpopulations contain cells
reactive with the MHC class I-like molecule CD1d. Murine NK cells express
clonally distributed inhibitory receptors of the Ly49 family that bind to
different alleles of MHC class I molecules and transmit negative signals
regulating NK cell function. Ly49 receptors are also found on TCRalphabeta+
NK1.1+ T cells. To investigate the potential role of inhibitory Ly49 markers in
the regulation of NKT cells, we have done a thorough analysis of their expression
on different NKT populations. The CD4+ and DN NK1.1+ T cell subsets have
traditionally been dealt with as one NK1.1+ T cell population, but we found
dramatic differences between these two NKT cell subsets. We demonstrate here
expression of Ly49 receptors on DN, but not on CD4+, NK1.1+ T cells in spleen and
liver. Absence of the specific MHC class I ligand in the host was associated with
elevated levels of expression and, to a greater extent than has been found for NK
cells, increased the frequencies of Ly49-positive cells within the DN subset,
while CD4+ NK1.1+ cells remained negative. In the thymus and bone marrow both
NK1.1+ T cell subsets contained high frequencies of Ly49-positive cells. Results
from in vitro stimulation of DN NKT cells further suggest that activation and
expansion of NKT cell subsets are regulated by the Ly49 receptors.
PMID- 11009082
TI - Binding of conserved islet peptides by human and murine MHC class II molecules
associated with susceptibility to type I diabetes.
AB - The major histocompatibility complex (MHC) is the most important susceptibility
locus for type I diabetes in humans and NOD mice. NOD mice express a single MHC
class II molecule (I-Ag7) which carries a unique beta chain sequence. In humans,
DQ alleles that encode DQ8 and DQ2 confer the highest risk for the disease.
Soluble DQ8 and I-Ag7 were used to directly compare the binding specificity of
these MHC molecules. Peptides from three islet antigens--insulin, GAD 65 and HSP
60--bound to both CQ8 and I-Ag7. These peptides included epitopes that are
immunodominant in NOD mice, namely insulin (9-23), GAD (206-220) and HSP 60 (441
460). All of these peptide sequences are highly conserved between the human and
murine antigens. The binding specificity of DQ8 and I-Ag7 was similar, but not
identical, since two peptides eluted from splenocytes of NOD mice did not bind to
DQ8. DQ8 formed long-lived complexes with the majority of these peptides,
indicating that DQ8 is not a poor peptide binder. These results demonstrate
functional similarities between human and murine MHC class II molecules that
confer susceptibility to type I diabetes.
PMID- 11009083
TI - Differential requirement of perforin and IFN-gamma in CD8 T cell-mediated immune
responses against B16.F10 melanoma cells expressing a viral antigen.
AB - Perforin-mediated lysis and secretion of IFN-gamma belong to the key effector
functions of CD8 T cells. To compare the anti-tumor activity of these two
mechanisms, we used B16.F10 melanoma cells (B16GP33) expressing the cytotoxic T
cell epitope GP33 and T cell receptor transgenic (TCR-tg) mice specific for GP33
and deficient in perforin or IFN-gamma. B16GP33 tumor cells, injected either i.v.
to induce experimental metastases or s.c., were similarly controlled in both wild
type and perforin-deficient, but not in IFN-gamma-deficient TCR-tg mice. A
similar result was obtained when the therapeutic efficacy of adoptively
transferred TCR-tg effector cells from these mice was examined in the
corresponding perforin- or IFN-gamma-deficient C57BL/6 hosts. Criss-cross
experiments further revealed that IFN-gamma production by the host strongly
influenced the efficiency of the adoptively transferred effector cells. In
contrast to the potent ability of GP33-specific effector cells to mediate B16GP33
tumor regression without perforin, GP33-specific memory cells, induced with
recombinant vaccinia virus expressing GP33, failed to control B16GP33 tumor
growth in the absence of perforin. In conclusion, our data demonstrate a crucial
role for IFN-gamma in B16GP33 tumor cell elimination in vivo and indicate a
differential requirement of perforin by effector versus memory CD8 T cells in
anti-tumor immunity.
PMID- 11009084
TI - Study of the B cell memory compartment in common variable immunodeficiency.
AB - We evaluated the B cell memory pool among blood B cells from 20 patients with
common variable immunodeficiency (CVID). CD27+ B cell number was normal or
increased in 6 patients (with 95% CD27+ B cells in 1 patient) and decreased in 14
patients. In 13 or 15 patients studied, the CD27 molecule was detectable on less
than 50% IgG or IgA B cells, indicating a defect in the maturation of these
memory cells. Within the group of patients with a low number of CD27+ B cells, no
up-regulation of this molecule was observed after in vitro stimulation of
purified B cells from 3 of 5 patients studied, suggesting an intrinsic B cell
defect. In addition, ligation of the CD27 molecule was unable to trigger terminal
differentiation of purified B cells in 1 of 2 cases with a large number of CD27+
B cells. Finally, the CD27 ligand was normally expressed on activated T cells in
only 5 of 14 patients studied. These data confirm the heterogeneity of
immunological defects in patients with CVID. Abnormal expression and/or function
of the CD27-CD70 members of the TNF/TNF receptor family contribute to the
immunological defect.
PMID- 11009085
TI - A single CTL clone can recognize a naturally processed HIV-1 epitope presented by
two different HLA class I molecules.
AB - Although it is known that a single peptide can be recognized by CTL restricted to
two MHC class I alleles, there is no direct evidence for presentation of a single
peptide by two MHC class I molecules. Furthermore, it is unclear whether such
peptides are presented to the same T cell or to different T cells. Our previous
study suggested that CTL recognition of the human immunodeficiency virus-1 (HIV
1) Pol HIV-B35-SF2-24 epitope (IPLTEEAEL) occurs via both HLA-B35 and HLA-B51
restriction. Here we provide the first direct evidence that a single CTL clone
can recognize this peptide presented by both HLA-B35 and HLA-B51. Furthermore, we
directly purified this peptide eluted from both HLA-B*3501 and HLA-B*5101
molecules isolated from target cells infected with HIV-1 recombinant vaccinia
virus. These results demonstrate that HIV-B35-SF2-24 is a naturally processed
peptide which is presented by both HLA-B*3501 and HLA-B*5101. TCR analysis of one
CTL clone suggested that it is a single clone. B*3501-SF2-24-tetrameric complexes
inhibited both HLA-B*3501- and HLA-B*5101-restricted recognition of this clone,
suggesting that the TCR of this clone cross-recognize the structure of both HLA
class I-peptide complexes.
PMID- 11009086
TI - A global appraisal of immunodominant CD8 T cell responses to Epstein-Barr virus
and cytomegalovirus by bulk screening.
AB - Knowledge of the immunodominant responses to Epstein-Barr Virus (EBV) and human
cytomegalovirus (HCMV) should help to generate cytotoxic T cell lines to these
herpesviruses. Here we report on the analysis of CD8 T cell responses to EBV and
HCMV in the blood of kidney transplant recipients undergoing viral reactivation
(n = 16) and in healthy virus carriers (n = 10). We used a transient COS
transfection assay that permits semi-quantitative estimation of CD8+ T cell
responses against a larger number of HLA/viral protein combinations within
polyclonal T cell lines and thus allows a rapid identification of major epitopes.
From the comparison of these responses to those that we previously described in
the synovial fluid of patients suffering from various forms of chronic arthritis
(n = 32), it appears that EBV-specific T cells are mainly directed against a
restricted set of immunodominant epitopes, primarily generated during the early
lytic cycle and that both IE1 and pp65 are targets of the anti-HCMV response. We
suggest that this method could be generally applied to the rapid identification
of immunodominant T cell epitopes in viral and tumor immunity, and could help
selecting HLA-peptide complexes that could be used to detect and sort specific T
cell populations.
PMID- 11009087
TI - The herpes simplex virus type 1 Fc receptor discriminates between IgG1 allotypes.
AB - Herpes simplex virus type 1 (HSV-1) expresses a complex of two virally encoded
glycoproteins, gE and gl, which is capable of binding nonimmune human IgG. The gE
gl complex has thus become known as an Fc receptor (FcR), which reportedly binds
human IgG subclasses in the order IgG4 > IgG1 > or = IgG2 and does not bind IgG3
from many individuals. There is, however, allelic variation in the genes encoding
the human IgG1 heavy chain constant region and this gives rise to allotypes of
IgG1. Using recombinant monoclonal IgG molecules of known isotype and mutants
thereof we have unexpectedly discovered that the HSV-1 FcR discriminates between
IgG1 allotypes. This is evidence of functional differences between IgG1 allotypes
that may account for their distribution in populations. Furthermore, these
findings suggest HSV-1 FcR binding sites on the IgG molecule some distance from
the proposed binding site in the CH2-CH3 domain interface.
PMID- 11009088
TI - Role of CD154 in the secondary immune response: the reduction of pre-existing
splenic germinal centers and anti-factor VIII inhibitor titer.
AB - Using the murine model of hemophilia A, we have examined the role of CD154 in the
secondary immune response to factor VIII (FVIII). We previously reported that
repeated i.v. injection of FVIII in hemophilia A mice induces a T cell-dependent
anti-FVIII antibody formation. Herein, blocking of CD154 by a monoclonal antibody
in FVIII-primed hemophilia A mice resulted in the disappearance of pre-existing
spleen germinal centers (GC) in the white pulp within 24 h of treatment.
Moreover, further expansion of GC in response to FVIII challenge was completely
inhibited. In parallel, anti-FVIII antibody titers were markedly reduced and T
cell responses to FVIII were abolished. The rapid disappearance of the GC after
anti-CD154 treatment was not accompanied by increased B cell apoptosis; instead B
cells accumulated in the peripheral zone of the splenic white pulp.
Interestingly, repeated exposure to FVIII with anti-CD154 antibody administration
blocked anti-FVIII antibody formation but failed to induce long-lasting
unresponsiveness. Our data demonstrate that the CD40-CD154 interaction is
critical for B cell homeostasis and the secondary immune response to FVIII. For
potential clinical application, the data also suggest that therapies targeting
the CD154 molecule may be useful for the treatment of high titer FVIII inhibitors
in hemophilia A.
PMID- 11009089
TI - Peroxovanadium-mediated protection against murine leishmaniasis: role of the
modulation of nitric oxide.
AB - The phosphotyrosine phosphatase inhibitor bpV(phen) has the ability to markedly
decrease the progression of leishmaniasis in vivo. Here, we have identified the
mechanisms that are responsible for this protective effect. We report that two
potent peroxovanadium (pV) compounds, bpV(phen) and bpV(pic), control progression
of leishmaniasis in a similar manner by modulating NO-dependent microbicidal
action. We observed that their injection can rapidly and transiently induce the
expression of inducible NO synthase (iNOS) in livers of mice and enhance
circulating nitrate levels. Treatment of mice with bpV(phen) or bpV(pic)
completely controlled progression of leishmaniasis in an NO-dependent manner,
since inhibition of iNOS with aminoguanidine completely reversed this pV-mediated
protection. This NO-dependent pV-mediated protection was further demonstrated by
the incapacity of bpV(phen)-treated Nramp-/-, iNOS-/- mutant mice to control
Leishmania major infection. Using an air pouch model, we showed that bpV(phen)
can strongly modulate secretion of L. major-induced pro-inflammatory molecules
and neutrophil recruitment. In addition, we observed that bpV(phen) per se can
strongly induce the expression of Th1 type cytokines over Th2 in spleens of
animals. Overall, this study has allowed us to establish the in vivo functional
and immunological events involved in pV-mediated protective mechanism against
leishmaniasis and that NO plays a pivotal role in this process.
PMID- 11009090
TI - Interleukin-12 and Flt3 ligand differentially promote dendropoiesis in vivo.
AB - Interleukin-12 (IL-12) and Flt3 ligand (FL) regulate hematopoiesis by stimulating
proliferation, differentiation and migration of progenitor and/or stem cells. In
this study, we evaluated the in vivo effect of IL-12 alone or in combination with
FL on dendritic cell (DC) generation and accumulation in murine spleen, lymph
node, thymus, liver, and tumor tissues. Both cytokines induced accumulation of
functional DC in lymphoid and non-lymphoid tissues. IL-12 promoted predominantly
myeloid dendropoiesis, while FL induced both myeloid and lymphoid dendropoiesis.
Combination treatment resulted in a dramatic increase in CD86+, and particularly,
NLDC-145+ cells within the liver, which was largely due to cell proliferation.
Combination therapy also revealed the ability of FL to protect bone marrow cell
populations from IL-12-induced depletion in vivo. In vitro, we found a
significant FL-induced up-regulation of IL-12 production by DC at both mRNA and
protein levels. Thus, our study suggests that (i) the antitumor activity of IL-12
may, at least in part, be mediated by the stimulation of dendropoiesis and (ii)
IL-12 might contribute to the antitumor activity of FL. Furthermore, induction of
DC generation in vivo by a combination of IL-12 and FL might become a new
approach for immunotherapy of cancer.
PMID- 11009091
TI - C/EBPbeta enhances IL-4 but impairs IL-2 and IFN-gamma induction in T cells.
AB - C/EBP transcription factors have been described to control the activity of the
human IL-4 promoter. The C/EBP binding sites within the IL-4 promoter overlap
with composite NF-AT and AP-1 binding motifs. We show here that similar binding
sites are part of the murine IL-4 promoter. Retroviral overexpression of
C/EBPbeta in murine EL-4 thymoma cells led to a strong induction of endogenous IL
4 and a reduction in IL-2 and IFN-gamma expression. Similarily, in primary murine
T cells C/EBPbeta induction resulted in an increase in IL-4 levels, whereas in
human Jurkat T cells a decrease in IL-2 RNA was detected. Like AP-1, C/EBP
factors belong to the large class of basic leucine zipper proteins. However,
unlike AP-1, C/EBPbeta does not act in synergy with NF-AT in the induction of the
murine IL-4 promoter. Instead, both factors compete in their binding to the P4/Pu
bD site, one of the most important sequence elements of the IL-4 promoter.
Whereas NF-AT factors require high levels of free Ca2+ and calcineurin activity
for induction, C/EBP induction in T cells is Ca2+/calcineurin independent. These
observations suggest that various induction conditions lead to the activation of
transcription factors, inducing IL-4 promoter activity at specific developmental
stages of T cells.
PMID- 11009092
TI - Sex steroids induce apoptosis of CD8+CD4+ double-positive thymocytes via TNF
alpha.
AB - T cell production by the thymus, thymic size, cellularity and output all decrease
drastically after puberty. Among the candidates that may mediate this decrease
are the sex steroids: hypersecretion or pharmacological administration of these
hormones has long been known to induce thymic hypocellularity, and their
depletion yields thymic hypercellularity. Here we show that a typical sex
steroid, testosterone, specifically targets CD8+CD4+ double-positive (DP)
thymocytes for apoptosis via TNF-alpha. Anti-TNF-alpha monoclonal antibodies
abrogated testosterone-induced DP apoptosis, and TNF-alpha-/- DP thymocytes were
largely resistant to testosterone-mediated apoptosis in vivo. Testosterone
accomplished this effect by upregulating TNF-alpha production and by
simultaneously sensitizing DP thymocytes to TNF-alpha. Thus, TNF-alpha is the
critical mediator of sex steroid-induced apoptosis in thymocytes, and its
manipulation should provide a point of intervention to modulate T cell production
in sex hormone disorders.
PMID- 11009093
TI - Locally inducible CD66a (CEACAM1) as an amplifier of the human intestinal T cell
response.
AB - CD66a is an adhesion molecule member of the carcinoembryonic antigen
immunoglobulin-like family present on the surface of epithelial cells,
granulocytes and IL-2 activated T cells. We studied whether CD66a is expressed in
vivo by T lymphocytes and whether it affects TCR-mediated activation. CD66a was
detected by histochemistry, flow cytometry analysis, reverse transcription PCR
and Western blot on fresh colon biopsies and T cell clones. A fraction of T cells
in the lamina propria express CD66a, which is induced by IL-7 and IL-15
cytokines. T cells express four different CD66a splice variants and at least two
forms of the protein are glycosylated in a cell type-specific manner. Triggering
of CD66a on T cells with physiological ligands or with specific mAb increases TCR
mediated lymphokine release, in an antigen dose-independent manner. This effect
requires the presence of the CD66a intracytoplasmic domain, which contains two
immunoglobulin receptor family tyrosine-based inhibitory motif-like domains, as
shown by stimulation of Jurkat cells transfected with different CD66a isoforms
and is associated with increased induction of AP1 and NFkappaB transcription
factors. These data indicate that CD66a amplifies T cell activation and thus
could facilitate crosstalk between epithelial cells and T lymphocytes in
intestinal immune response.
PMID- 11009094
TI - Identification of an IFN-gamma responsive region in an intron of the invariant
chain gene.
AB - The mechanism by which IFN-gamma up-regulates invariant chain mRNA in antigen
presenting cells has been under intensive investigation. This study shows that in
murine monocytic cells the transcriptional up-regulation mediated by the
invariant chain (Ii) upstream enhancer only accounts for part of the induction of
Ii mRNA by IFN-gamma. We have identified an intronic region in the murine Ii gene
that contributes to the transcriptional up-regulation by IFN-gamma. The region
has S (H), X/X2 and Y boxes similar to those in MHC class II promoters and the Ii
upstream enhancer. Mutations at the putative S, X and Y boxes have abolished the
ability of the region to mediate Ii up-regulation by IFN-gamma. Consistent with
the functions of these boxes, our findings reveal that the up-regulation of Ii
transcription by IFN-gamma mediated by the intronic region is dependent on the
induction of class II transactivator by IFN-gamma.
PMID- 11009095
TI - MHC class II and CD40 play opposing roles in dendritic cell survival.
AB - In contrast to very immature dendritic cells (DC), mature DC are largely
resistant to death by CD95 (CD95/APO-1) ligation. Investigation of other
potential death-inducing ligands showed that mature DC were instead highly
susceptible to apoptosis induced by cross-linking of MHC class II. Thus,
increasing DC maturity correlates with increased resistance to CD95 killing, but
an increased susceptibility to class II-mediated killing. Anti-I-A/I-E monoclonal
antibodies (mAb) induced rapid (<2 h) apoptotic cell death in mature epidermal,
spleen and bone marrow-derived DC, as determined by annexin/propidium iodide
staining, morphological changes, decreased diploidy and loss in mitochondrial
membrane potential. Although full class II-mediated killing required DC
cytoskeletal motion, divalent cations and phosphatase activity, neither caspase
activation, respiration, RNA or protein synthesis, NO production, nor CD95:CD95L
interactions were required. Strikingly, DC pretreated by CD40 mAb cross-linking,
but not by lipopolysaccharide or TNF-alpha, were completely resistant to class II
mediated killing. CD40-mediated protection was reduced in the presence of the
SB202190 inhibitor of the mitogen-activated protein kinase p38 pathway, but
appeared to be independent of p42/44 extracellular signal-related kinase or NF-KB
activation. Our findings show that in addition to its role as an activator of
antigen-presenting cell function, CD40 provides an important counter-signal
against class II-induced apoptosis. Thus, these data point to an important role
of the T cell in regulating DC survival.
PMID- 11009096
TI - Temporally regulated assembly of a dynamic signaling complex associated with the
activated TCR.
AB - TCR triggering promotes multiple tyrosine kinase-dependent interactions involving
proteins with one or more protein binding modules. Reported interactions mostly
exceed the binding potential of these proteins. A solution to this paradox is the
temporally regulated recruitment of alternative ligands. We have tested this
hypothesis by analyzing the time course of protein/protein interactions triggered
by TCR engagement. We show that a short-lived and dynamic multimolecular complex
is assembled on tyrosine-phosphorylated CD3zeta. Specific components of this
complex are recruited and shed in a temporal sequence distinct for each of the
proteins analyzed. The temporally regulated assembly of a higher order structure
at the activated TCR is likely to be crucial in achieving both signal longevity
and signal specificity.
PMID- 11009097
TI - Defective recruitment and activation of ZAP-70 in common variable
immunodeficiency patients with T cell defects.
AB - We have previously identified a subset of common variable immunodeficiency (CVID)
patients with defective T cell function associated with impaired activation of
the TCR-dependent tyrosine phosphorylation cascade. Here we have assessed the
structural and functional integrity of the principal components involved in
coupling the TCR/CD3 complex to intracellular tyrosine kinases in two of these
patients. We show that ZAP-70 fails to bind the signaling-competent CD3zeta
tyrosine phosphorylation isoform and to become activated following TCR
engagement, suggesting that defective recruitment of ZAP-70 might underlie the
TCR signaling dysfunction in these patients. Determination of the nucleotide
sequences encoding the intracellular domains of the CD3/zeta subunits and ZAP-70
did not reveal any mutation. Furthermore, ZAP-70 from these patients could
interact in vitro with recombinant phospho-zeta, ruling out genetic defects at
the immunoreceptor tyrosine-based activation motif/SH2 domain interface
responsible for ZAP-70 recruitment to the activated TCR. No defect was found in
expression, activity or subcellular localization of Lck, which is thought to be
primarily responsible for CD3zeta phosphorylation. Hence, while the T cell defect
in these CVID patients can be pinpointed to the interaction between ZAP-70 and
CD3zeta, the integrity in the components of the signaling machinery involved in
this process suggests that additional components might be required for completion
of this step.
PMID- 11009098
TI - TGF-beta1 down-regulates Th2 development and results in decreased IL-4-induced
STAT6 activation and GATA-3 expression.
AB - TGF-beta plays an important role in immune regulation in vivo and affects T cell
differentiation in vitro. Here we describe how TGF-beta modulates Th2 development
in vitro and investigate its mechanisms of action. TGF-beta down-regulated Th2
development of naive CD4+ Mel-14high T cells derived from the DO11.10 ovalbumin
specific TCR-transgenic mouse, and this was observed both in cultures driven with
anti-CD3 and anti-CD28 and with splenic APC and antigen. TGF-beta down-regulated
GATA-3 expression in developing Th2 and these cells showed a diminished IL-4
induced STAT6 activation. We found, however, that naive cells driven in Th2
conditions with TGF-beta did not show a significantly decreased STAT6 activation,
suggesting that TGF-beta inhibits Th2 development via a STAT6-independent
mechanism.
PMID- 11009099
TI - B7 co-stimulatory requirements differ for induction of immune responses by DNA,
protein and recombinant pox virus vaccination.
AB - Whether B7-1 and B7-2 have distinct functions for eliciting immune responses to
antigens that are presented to the immune system by intracellular and
extracellular antigen processing pathways is an unresolved question. To
investigate this issue we compared the humoral and cellular immune responses
elicited by immunizing wild-type, B7-1-/- and B7-2-/- mice with either HIV-1
gp120 plasmid DNA, recombinant gp120 protein or vaccinia virus expressing gp120.
The generation of both humoral and cellular immune responses to an antigen
produced intracellularly following DNA vaccination had critical requirements for
B7-2, but not B7-1. Neither of the molecules was essential for the generation of
antibody responses to an extracellular protein antigen administered with
adjuvant; B7-1 had little effect on the elicited immune responses. When
recombinant vaccinia virus was used to present antigen intracellularly in the
context of a viral infection, B7-2 was absolutely required for antibody and T
cell proliferative responses, but it exerted a suppressive effect on the elicited
CTL activity. These results demonstrate that antigens presented to the immune
system by different mechanisms have distinct B7-1 and B7-2 co-stimulatory
requirements.
PMID- 11009100
TI - MMCP-8, the first lineage-specific differentiation marker for mouse basophils.
Elevated numbers of potent IL-4-producing and MMCP-8-positive cells in spleens of
malaria-infected mice.
AB - In mice infected with the non-lethal malaria parasite Plasmodium chabaudi
chabaudi AS, a prominent switch from a Th1 to a Th2 type of response occurs in
CD4+ T cells at the time of peak parasitemia or shortly thereafter (9-15 days
after infection). This is accompanied by a major increase in IL-4, and a similar
decrease in IFN-gamma-producing cells. Non-B-non-T cells have been shown to be
the main source of the IL-4 in these mice. The IL-4-producing cells are
hyperresponsive to IL-3, indicating mast cell or basophil origin. To further
characterize this cell population we have studied various organs at different
time points of malarial infection by Northern blot analysis. No significant
increase in the expression of any of the classical mouse mast cell serine
proteases (MMCP)-1 to 7 or carboxypeptidase A was detected in the spleen during
the entire infection. However, a marked increase in the expression of MMCP-8 was
observed in the spleen at around day 15 post infection. Isolation of IgE receptor
positive cells from spleen shortly after peak parasitemia led to a prominent
enrichment of MMCP-8-expressing cells. Fifty thousand of these cells were, after
IL-3 stimulation, found to produce IL-4 to levels comparable with more than one
million fully activated T cells. Our results show that basophil-like cells are
very potent producers of IL-4 and that IL-4 produced by these cells may be of
major importance for the initiation of a Th2 response. In addition, the detection
of MMCP-8 in these cells has led to the identification of the first basophil
specific differentiation marker in the mouse.
PMID- 11009101
TI - Alternatively activated macrophages induced by nematode infection inhibit
proliferation via cell-to-cell contact.
AB - The cytokine microenvironment is thought to play an important role in the
generation of immunoregulatory cells. Nematode infections are commonly associated
with Th2 cytokines and hyporesponsive T cells. Here we show that IL-4-dependent
macrophages recruited in vivo by the nematode parasite Brugia malayi actively
suppress the proliferation of lymphocytes on co-culture in vitro. These
alternatively activated macrophages block proliferation by cell-to-cell contact,
implicating a receptor-mediated mechanism. Further, the proliferative block is
reversible and is not a result of apoptosis. Suppressed cells accumulate in the
G1 and G2/M phase of the cell cycle. Interestingly, the G1 and G2/M block
correlates with increased levels of Ki-67 protein, suggesting a mechanism that
affects degradation of cell cycle proteins. We also show that, in addition to
lymphocyte cell lines of murine origin, these suppressive cells can inhibit
proliferation of a wide range of transformed human carcinoma lines. Our data
reveal a novel mechanism of proliferative suppression induced by a parasitic
nematode that acts via IL-4-dependent macrophages. These macrophages may function
as important immune regulatory cells in both infectious and noninfectious disease
contexts.
PMID- 11009102
TI - The synthetic, oxidized C-terminal fragment of the Plasmodium berghei
circumsporozoite protein elicits a high protective response.
AB - A polypeptide of 69 amino acids (PbCS 242-310) encompassing the C-terminal region
of the circumsporozoite protein of Plasmodium berghei (PbCS) was generated using
solid-phase peptide synthesis. The immunological and protective properties of
peptide PbCS 242-310 were studied in BALB/c mice (H-2d). Two subcutaneous
injections, in the presence of IFA at the base of the tail, generated (i) high
titers of anti-peptide antibodies which also recognized the native P. berghei CS
protein, (ii) cytolytic T cells specific for the Kd-restricted peptide PbCS 245
253 and (iii) partial CD8+-dependent protection against sporozoite-induced
malaria. The same frequencies of peptide PbCS 245-253 specific CD8+ T cells were
found by IFN-gamma ELISPOT in the draining lymph nodes of animals immunized with
the short optimal CTL peptide 245-253 or with the polypeptide 242-310, indicating
that the longer polypeptide can be processed and presented in vivo in the context
of MHC class I as efficiently as the short CTL peptide. Interestingly, higher
levels of IFN-gamma producing CD8 T cells and protection were observed when the
four cysteine residues present in the C-terminal peptide were fully oxidized.
These findings underline the potential importance of the chemical nature of the C
terminal fragment on the activation of the immune system and concomitant
protection.
PMID- 11009103
TI - Regulation of cell survival during B lymphopoiesis: increased pre-B cell
apoptosis in CD24-transgenic mouse bone marrow.
AB - CD24 (heat-stable antigen) is expressed in a developmentally regulated fashion by
B cell precursors in mouse bone marrow (BM), but its role in B lymphopoiesis
remains obscure. A slight overexpression of CD24 in transgenic (Tg) mice leads to
depletion of B lymphoid cells in BM. The present study examines whether CD24 is
involved in apoptotic selection of B lineage cells under normal
microenvironmental conditions in vivo. Double immunofluorescence labeling and
flow cytometry have been used to quantitate the apoptotic rates of phenotypically
defined B cell populations in BM of CD24-Tg mice. Apoptosis of pre-B cells
expressing cytoplasmic mu heavy chains of IgM but lacking surface (s)IgM was
increased both ex vivo and in short-term culture, while the number of pre-B cells
was halved compared to BM of normal mice. In contrast, B220+mu- pro-B cells and
sIgM+ B lymphocytes showed no significant change in either apoptosis or number.
The findings provide evidence that CD24 can play a role in vivo in modulating pre
B cell apoptosis, a quality control checkpoint in B cell development.
PMID- 11009104
TI - A disulfide-linked natural killer cell receptor dimer has higher affinity for HLA
C than wild-type monomer.
AB - Inhibitory receptors on the surface of natural killer (NK) cells recognize
specific MHC class I molecules on target cells and prevent the target cell lysis
by NK cells. The killer cell immunoglobulin-related receptors (KIR), KIR2D, found
in human, specifically interact with polymorphic HLA-C molecules. The crystal
structure of the inhibitory receptor, KIR2DL1, revealed a relationship to the
hematopoietic receptor family, suggesting that the signaling mechanism of KIR2D
molecules may resemble that of the hematopoietic receptors, and involve KIR2D
dimerization. We have engineered a disulfide-linked dimer of KIR2DL1 by
introducing a free cysteine at the C-terminal stem region of the receptor. The
disulfide-linked KIR2DL1 dimer binds to HLA-Cw4 at a molar ratio of one dimer to
one HLA-Cw4 molecule. Furthermore, the covalently-linked KIR2DL1 dimer binds more
tightly to HLA-Cw4 than the wild-type monomer, suggesting the occurrence of a
second binding event that increases the overall affinity of KIR dimer for HLA-C.
PMID- 11009105
TI - Interleukin-4 transgenic mice develop glomerulosclerosis independent of
immunoglobulin deposition.
AB - Mice with constitutive transgenic (tg) expression of IL-4 develop autoimmune-type
disorders resembling human lupus nephritis. The kidneys show progressive
glomerulosclerosis with immunoglobulin (Ig) and complement deposition. This study
investigated the roles of renal IL-4 expression and glomerular Ig deposition in
the pathogenesis of glomerulosclerosis in IL-4 tg mice. Treatment of these mice
with IL-4 neutralizing antibody prevented renal disease. IL-4 tg mice treated
with methylprednisolone (MP) showed increased mesangial collagen deposition with
only trace amounts of glomerular Ig. To analyze the relevance of Ig deposition in
the development of the renal lesions, IL-4 tg mice were cross-bred with mu chain
deficient mice (muMT-/-), which are unable to produce Ig. IL-4 tg/muMT-/- mice
developed progressive glomerulosclerosis with mesangial accumulation of collagen
types I, IV and V despite complete absence of glomerular Ig deposits. Renal IL-4
expression was observed in both anti-IL-4- and MP-treated IL-4 tg mice as well as
in IL-4 tg/muMT-/- mice. No statistical difference in the number of glomerular T
cells and macrophages between any of the groups was evident. Our data demonstrate
that in this model glomerulosclerosis can develop independently of and prior to
Ig deposition, and suggest that the initial accumulation of glomerular
extracellular matrix is due to renal IL-4 expression. Our results point to a
novel mechanism for the development of glomerulosclerosis which may have
implications for human disease.
PMID- 11009106
TI - CD8 memory, immunodominance, and antigenic escape.
AB - Previous theoretical work has suggested that efficient virus control or clearance
requires antigen-independent persistence of memory cytotoxic T lymphocyte
precursors (CTLp), and that failure to generate such memory CTLp can result in
persistent infection and eventual loss of virus control. Here we use mathematical
models to investigate the relationship between virus control, the clonal
composition of the CTL response and the chance of the virus to evolve antigenic
escape. In the presence of efficient memory CTLp, virus is controlled at very low
levels by a broad CTL response directed against multiple epitopes. In this case,
antigenic escape of the virus population is expected to take a very long time. On
the other hand, if the CTL response is short lived in the absence of antigen,
virus replicates at higher levels and is only opposed by a narrow CTL response,
characterized by an immunodominant CTL clone. In this case, antigenic escape is
expected to evolve in a short period of time, resulting in progressive loss of
virus control. We discuss our findings in relation to data from HIV-1-infected
patients.
PMID- 11009107
TI - High frequencies of circulating IFN-gamma-secreting CD8 cytotoxic T cells
specific for a novel MHC class I-restricted Mycobacterium tuberculosis epitope in
M. tuberculosis-infected subjects without disease.
AB - MHC class I-restricted CD8 cytotoxic T lymphocytes (CTL) are essential for
protective immunity to Mycobacterium tuberculosis in animal models but their role
in humans remains unclear. We therefore studied subjects who had successfully
contained M. tuberculosis infection in vivo, i.e. exposed healthy household
contacts and individuals with inactive self-healed pulmonary tuberculosis. Using
the ELISPOT assay for IFN-gamma, we screened peptides from ESAT-6, a secreted
antigen that is highly specific for M. tuberculosis. We identified a novel
nonamer epitope: unstimulated peripheral blood-derived CD8 T cells displayed
peptide-specific IFN-gamma release ex vivo while CD8 T cell lines and clones
exhibited HLA-A68.02-restricted cytolytic activity and recognized endogenously
processed antigen. The frequency of CD8 CTL specific for this single M.
tuberculosis epitope, 1/2500 peripheral blood lymphocytes, was equivalent to the
combined frequency of all IFN-gamma-secreting purified protein derivative
reactive T cells ex vivo. This highly focused CTL response was maintained in an
asymptomatic contact over 2 years and is the most potent antigen-specific
antimycobacterial CD8 CTL response hitherto described. Thus, human M.
tuberculosis-specific CD8 CTL are not necessarily associated with active disease
per se. Rather, our results are consistent with a protective role for these ESAT
6-specific CD8 T cells in the long-term control of M. tuberculosis in vivo in
humans.
PMID- 11009108
TI - CD45R, CD44 and MHC class II are signaling molecules for the cytoskeleton
dependent induction of dendrites and motility in activated B cells.
AB - Anti-CD44 or anti-MHC II antibodies bound to tissue culture plates have
previously been shown to induce a dramatic generation of dendritic processes in
activated murine B cells. In this study, we demonstrate a similar generation of
dendrites and cell motility in activated B cells through CD45R. The dynamic
formation of dendritic processes and associated induction of cell motility were
analyzed by video microscopy and were characterized by a rapid, and
multidirectional emission of dendrites with retractile behavior. The addition of
cytochalasin E totally blocked dendrites formation and motility induced through
either CD45R, CD44 or MHC II, suggesting that the necessary cytoskeletal
rearrangements require active polymerization of actin. Confocal microscopy showed
an accumulation of F-actin in the dendrites, as long as cells were elongating. In
contrast, G-actin was localized in the perinuclear area and also accumulated in
sites where dendrites originated. Preincubation of B cells with staurosporine (a
PKC inhibitor) or BAPTA-AM (a calcium chelator) prevented these morphological
changes, indicating additionally a requirement for a PKC-calcium-dependent
activity. Dendrite formation and cellular motility, therefore, seem to be two
manifestations of the same phenomenon, and CD44, CD45R and MHC II appear to be
signaling molecules for the observed cytoskeleton-dependent morphological
changes.
PMID- 11009109
TI - In experimental leishmaniasis deficiency of CD18 results in parasite
dissemination associated with altered macrophage functions and incomplete Th1
cell response.
AB - We investigated experimental leishmaniasis in CD18-deficient mice. Whereas wild
type (WT) CD18-/- mice (129SV/C57BL/6) were resistant to infection, CD18-/- mice
revealed increasing visceral dissemination of parasites. Unlike in other
susceptible strains, infected footpads of CD18-/- mice did not ulcerate, due to
an abolished recruitment of granulocytes. In vitro, CD18-/- macrophages were able
to phagocytose opsonized Leishmania major despite absence of CR3, albeit
phagocytosis rate was 50% lower than in WT macrophages. We found that uptake was
partially mediated by scavenger receptors. As infected CD18-/- macrophages showed
impaired ability to produce NO and to eliminate parasites, CD18 is one mediator
of NO production. CD18 is also involved in reduction of IL-12 release by L. major
infected macrophages, as uptake of opsonized parasites (via CR3) decreased IL-12
release only in WT, but not in CD18-/- macrophages. When T cells from infected
CD18-/- mice were restimulated with antigen-presenting cells (APC), they released
no IL-2 or IL-4, but a little IFN-gamma, associated with lack of proliferation.
This deficiency was linked to absence of CD18 on T cells, but not on APC.
Substitution with IL-2 specifically restored a Th1-like response with
proliferation and release of IFN-gamma. Thus, while impaired phagocytosis, NO
production, and recruitment of granulocytes in CD18-/- mice may not reverse
resistance, and while unrestricted IL-12 release supports development of Th1
cells, the failure of T cells to release IL-2 and to proliferate causes
susceptibility.
PMID- 11009110
TI - Removal of parvovirus B19 from hemoglobin solution by nanofiltration.
AB - Parvovirus B19 (B19), which may contaminate red cell components for blood
transfusion, is known to be resistant to several viral inactivation methods. To
increase the safety of hemoglobin solutions as a source of red cell substitutes,
we investigated the removal of parvovirus B19 from hemoglobin solution using
nanofiltration. The hemoglobin solution spiked with parvovirus B19 was
tangentially filtered using the BMM-35 filter (mean pore size of 35 nm) followed
by BMM-15. The parvovirus B19 of 10(8.5) PT50 (median PCR titer)/10 microL was
not changed after the BMM-35 filtration. However, the BMM-15 filtration decreased
the parvovirus B19 from 10(8.3-8.7) PT50 to 10(1.3-2.2) PT50, indicating more
than 6 log10 reduction. When the initial parvovirus B19 of 10(6.0) PT50 was
subjected to the BMM-15 filtration, the residual virus was 10(-0.3-0.5) PT50
orundetected in some fraction of the filtrate. Hemoglobin recovery was 70.4 +/-
3.4%. The ratio of methemoglobin was not changed during the filtration. These
findings indicate that the BMM-15 filtration is a promising approach to prepare a
safer hemoglobin solution for red cell substitutes.
PMID- 11009111
TI - Effect of alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) on the potency of
sodium nitroprusside and nitroglycerine to decrease blood pressure in rats: a
dose-response study.
AB - The nitrovasodilators, sodium nitroprusside and nitroglycerine, effect a dose
dependent decrease in mean arterial blood pressure (MABP) by liberating nitric
oxide. Alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) is known to bind
nitric oxide. We studied the effect of DCLHb on the potency of sodium
nitroprusside (n=36) and nitroglycerine (n=36) to decrease MABP in rats which
received 1, 10, 100, 1,000, or 10,000 mg/kg of the DCLHb, or normal saline as the
Control. Six doses of sodium nitroprusside or nitroglycerine were given to each
rat in a systematically varied sequence. For both drugs, in rats given 1, 10, or
100 mg/kg of DCLHb there were no between groups differences in the change in MABP
compared to the Control group. For rats that received 1,000 or 10,000 mg/kg of
DCLHb, the potency of nitroglycerine and sodium nitroprusside to decrease MABP
was less (p<0.05) than the other groups. These data support the hypothesis that
small doses of DCLHb effect a minimal change in the potency of nitrovasodilators
to reduce blood pressure. However, they suggest that clinically relevant doses of
DCLHb attenuate the vasodilatory ability of sodium nitroprusside and
nitroglycerine.
PMID- 11009113
TI - A novel immunoadsorbent for rheumatoid arthritis therapy--preparation and
efficacy evaluation.
AB - AIM: To develop a novel immunoadsorbent for rheumatoid arthritis (RA) therapy.
METHODS: A RA immunoadsorbent was developed by binding heat-aggregated human
IgG(HAHIgG) to porous agar gel beads. Its adsorption capacity for rheumatoid
factors (RFs), storage stability and blood compatibility were evaluated. RESULTS:
The coupling yield of HAHIgG on the carrier was 6.0 mg/g wet gel. Saturation
adsorption capacity of the adsorbent for IgMRF, IgGRF and IgARF were 3400, 2240
and 2400 IU/g, respectively. The adsorbent can be stored at 4 degrees C for three
months without significant variance in its activity. Its fine permeability and
hemocompatibility were demonstrated by extracorporeal hemoperfusion on rabbits.
CONCLUSION: HAHIgG/agar gel is a safe and effective immunoadsorbent for RA
therapy, its potential clinical use is promising in the future.
PMID- 11009112
TI - Artificial cells microencapsulated genetically engineered E. coli DH5 cells for
the lowering of plasma creatinine in-vitro and in-vivo.
AB - High level of plasma creatinine occurs in renal insufficiency, uremia, and other
diseases. At present lowering of this metabolite is done by using dialysis and
other techniques. In this article, we report the use of artificial cells
microencapsulated genetically engineered E. coli DH5 cells for lowering plasma
creatinine in-vitro and in-vivo. Result shows that artificial cells were able to
lower plasma creatinine in-vitro from 21.80 +/- 1.10 mg/dl to 21.80 +/- 1.10
mg/dl in 60 minutes and to 19.34 +/- 0.60 mg/dl in 3 hours. Result also shows
that when given orally on a daily basis, artificial cells microencapsulated
genetically engineered E. coli DH5 cells were also able to lower plasma
creatinine in rats.
PMID- 11009114
TI - Effects of liposome-encapsulated ciprofloxacin on phagocytosis, nitric oxide and
intracellular killing of Staphylcoccus aureus by murine macrophages.
AB - The effects of liposome-encapsulated ciprofloxacin on phagocytosis, nitric oxide
production and intracellular killing of Staphylococcus aureus in murine
macrophages were evaluated in this study. Mice were pretreated with three daily
doses of liposome-encapsulated ciprofloxacin (45 mg/kg body weight/dose,
intraperitoneal injection). At day 3 post drug administration, peritoneal
macrophages were harvested by peritoneal lavage, and the phagocytic activity of
the macrophages was determined by a chemiluminescence assay using opsonized
zymosan particles. The phagocytic activity was found to be 7-fold higher in the
liposome-encapsulated ciprofloxacin-treated group when compared to the untreated
control group. For S. aureus-infected macrophages incubated with liposomes
containing subinhibitory concentrations of ciprofloxacin (0.05 to 0.25
microg/mL), there were significant increases (up to 40 microM) in the levels of
nitrite (NO2-, an end product of nitric oxide synthesis), and concommitant
decreases (2-3 log) in the intracellular concentrations of S. aureus. Peak
nitrite levels (20-40 microM) were produced when concentrations of liposome
encapsulated ciprofloxacin used were 0.1 to 0.25 microg/mL. These results suggest
that liposome-encapsulated ciprofloxacin may have profound effects on the
immunological functions of macrophages.
PMID- 11009115
TI - Plasmapheresis in life-threatening verapamil intoxication.
AB - Verapamil intoxications are life-threatening conditions with a far too often
fatal outcome. In 2 patients, severe suicidal intoxication by 2.4 g and 9.6 g of
verapamil orally resulted in life threatening hypotension and bradycardia with
the need of heart-pacing and resuscitation. Plasmapheresis was started within
less then 4 hours after intoxication and seemed to reduce the verapamil plasma
concentration to less then 40%. A dramatic improvement of cardiovascular
stability was already observed during plasmapheresis. In-vitro plasmapheresis was
performed to verify the effectiveness of the extracorporeal detoxification.
Verapamil was removed out of the blood by a clearance of 29.2 ml/min at blood
flow of 200 ml/min. In conclusion, severe verapamil poisoning should be treated
by early aggressive gut decontamination and an appropriate management of the
haemodynamic complications. In case of lack of effectiveness for stabilisation,
plasmapheresis can reduce verapamil related life threatening symptoms and bridge
the time for the hepatic detoxification.
PMID- 11009117
TI - Preventing scientific misconduct--times have changed.
PMID- 11009116
TI - Assessment of low-power laser biostimulation on chondral lesions: an "in vivo"
experimental study.
AB - The purpose of this study was to evaluate whether intraoperative laser
biostimulation can enhance healing of cartilaginous lesions of the knee. Surgery
was performed on eighteen rabbits: a bilateral chondral lesion of 1.25 +/- 0.2 mm
in length and 0.8 +/- 0.2 mm in width was created in the femoral medial condyle
with a scalpel. The lesion in the left knee of each animal was treated
intraoperatively using the diode Ga-Al-As 780nm. laser (300 Joules/cm2, 1 Watt,
300 Hertz, 10 minutes), while the right knee was left untreated, as control
group. The animals were divided into three groups, A, B and C, according to the
survival time after surgery, two, six and twelve weeks, respectively. The
explants from the femoral condyles, both treated employing laser energy and left
untreated, were examined histologically. Results showed a progressive filling
with fibrous tissue of the cartilaginous lesion treated with laser irradiation,
while no changes in the original lesion of the untreated group were observed at
the end of the study. Maybe, in this experimental research, underexposure to
laser irradiation was the cause for the absence of the necessary conditions for
biostimulation.
PMID- 11009118
TI - Alternative technique for medication injections.
PMID- 11009119
TI - Effects of surgery type and attention focus on children's coping.
AB - BACKGROUND: How children cope with minor or major surgery is influenced by their
attention focus appraisals. Although factors that predict children's coping with
surgery have been identified (i.e., age, locus of control, parent-doctor
information, worry), it still is not known whether the type of surgery per se
affects the coping strategies used and influences previously established
predictors of coping. Furthermore, questions remain concerning the relation among
type of surgery, attention focus, and coping. OBJECTIVES: The purpose of this
study was to determine whether the type of surgery (minor vs. major) would have a
differential effect on coping, and whether coping can be predicted better if it
is known what type of attention focus (appraisal) the child has. METHODS: Data
from three studies of children (n = 189) undergoing minor or major surgery were
combined to examine the effects that type of surgery and attention have on
coping. Measures included the Preoperative Mode of Coping Interview, Locus of
Control Scale for Children, Parent-Doctor Information Interview, and a measure
for worry. RESULTS: The results showed that the factors previously found to
predict coping were upheld in the combined sample and accounted for 50% of the
variance in coping. Type of surgery was significantly associated with coping:
Children undergoing minor surgery were somewhat more vigilant than children
undergoing major surgery. The inclusion of attention in the analysis
significantly improved the variance explained in coping (66%), and children who
had a concrete-objective focus of attention were found to be more vigilant.
Significant interactions were found between attention focus and type of surgery,
locus of control, and age. Type of surgery also had a significant interaction
with worry. Children who focused on the concrete-objective aspects of the
situation were more vigilant if they were having minor rather than major surgery.
Also, children who had an internal locus of control and a concrete-objective
focus of attention were more vigilant in coping. Regardless of age, children who
had a concrete-objective focus of attention were more vigilant. Furthermore, at
low levels of worry, children undergoing major surgery were more vigilant than
children undergoing minor surgery. CONCLUSIONS: Coping with surgery is influenced
by multiple factors. Children's ability to focus attention on the concrete
objective aspects of surgery may help to reduce feelings of threat that could
impede their use of vigilant coping.
PMID- 11009120
TI - Hospital and emergency department use by young low-income children.
AB - BACKGROUND: Limited data are available concerning determinants of health care
service usage by low-income young children. OBJECTIVES: To explore predictors of
hospitalization and emergency department (ED) use by young children of low-income
families by using the Aday and Andersen Access Framework. METHODS: Low-income
women (n = 474) with a child younger than 6 years completed a structured face-to
face interview at human service offices or Women, Infants, and Children (WIC)
clinics in four central Ohio counties. Women were considered low-income if they
or their child were Medicaid eligible or uninsured. Data were collected for both
the mother and the index child on sociodemographic status, health services use,
health status, and access to care. RESULTS: Fifteen percent of the children had
been hospitalized the previous year, and half had an ED visit. Hospitalization
was significantly related to maternal hospitalization the previous year (OR =
2.5), child age younger than 1 year old (OR = 2.1) and more than two chronic
conditions (OR = 2.2). Maternal ED usage in the last year (OR = 2.2), Medicaid
fee for service plan (OR = 1.7), and rural residence (OR = 2.0) were predictive
of ED use. CONCLUSIONS: Predisposing characteristics (maternal hospital/ED use)
were predictive of both hospitalization and ED use by the index child. Enabling
characteristics (fee-for-service Medicaid plan, rurality) were only predictive of
ED use, and need characteristics (child's health) were only predictive of
hospitalization. Further research to explore linkages between maternal and child
use of health care services as well as the effect of changes in health care
access, managed care, and other innovations on hospitalization and ED use in
young, low-income children is recommended.
PMID- 11009121
TI - Self-esteem and optimism in men and women infected with HIV.
AB - BACKGROUND: Self-esteem and optimism have been associated with appraisal and
outcomes in a variety of situations. The degree to which the contribution of self
esteem and optimism to outcomes over time is accounted for by the differences in
threat (primary) or resource (secondary) appraisal has not been established in
persons with human immunodeficiency virus (HIV). OBJECTIVES: To examine the
longitudinal relationship of personality (self-esteem and optimism) on primary
and secondary appraisal and outcomes of well-being, mood, CD4+ T-lymphocyte
count, and selected activities. METHODS: Men (n = 56) and women (n = 42) infected
with HIV completed eight self-report measures twice over 18 months. Hierarchical
Multiple Regressions were used to examine the relationship of personality
variables on appraisals and outcomes. The mediating effects of primary and
secondary appraisals were explored. RESULTS: Self-esteem uniquely accounted for
6% of the variance in primary appraisal and 5% in secondary appraisal. Optimism
accounted for 8% of the unique variance in secondary appraisal. Primary and
secondary appraisal mediated differently between personality and outcome
variables. A strong predictor of well-being, mood disturbance, and activity
disruption at Time 2 was participants' initial level of these variables.
Socioeconomic status was a strong predictor of mood. CONCLUSIONS: Self-esteem and
optimism are important but different resources for adapting to HIV disease.
Strategies for reducing threats and increasing resources associated with HIV may
improve an individual's mood and sense of well-being.
PMID- 11009122
TI - Postpartum Depression Screening Scale: development and psychometric testing.
AB - BACKGROUND: Approximately 400,000 mothers in the United States experience
postpartum depression each year. However, only a small proportion of these women
are identified as depressed by health care professionals. OBJECTIVES: To improve
detection of this postpartum mood disorder, the purpose of this study was to
assess the psychometric properties of a newly devised instrument, the Postpartum
Depression Screening Scale (PDSS), a 35-item Likert-type self-report instrument.
METHODS: Content validity was supported through the literature and the judgments
rendered by a panel of five content experts and a focus group. The PDSS was
administered to 525 new mothers. RESULTS: Confirmatory factor analysis provided
empirical support for the existence of the hypothesized seven dimensions. A
Tucker-Lewis goodness-of-fit index of 0.87 and a root mean square residual of
0.05 were judged supportive of model fit. Item response theory techniques
provided further construct validity support for finer interpretations of the
respective seven dimensions. Analysis of the Likert 5-point response categories
further supported meaningful score interpretations. Alpha internal consistency
reliabilities ranged from 0.83 (sleeping/eating disturbances) to 0.94 (loss of
self). CONCLUSIONS: Empirically, all of the reliability and validity analyses
supported the score interpretations posited for the PDSS. Currently, the
sensitivity, specificity, and positive predictive value of the PDSS are being
determined.
PMID- 11009123
TI - The effect of structured training on breast self-examination search behaviors as
measured using biomedical instrumentation.
AB - BACKGROUND: Although breast self-examination (BSE) has long been recommended by
health care practitioners as a complement to mammography and clinical breast
examination, only a small percentage of U.S. women report doing monthly BSE, and
an even smaller number of women perform this procedure proficiently. OBJECTIVES:
To measure the effect of a structured training protocol on improving two
dimensions of BSE technique (depth of palpation and search time) in each of two
search patterns (vertical strip and concentric circle) using biomedical
instrumentation. METHODS: For this study, 41 young women participated in a
structured training protocol for BSE instruction. The dependent variable was
thoroughness of search, for which there were two measures: depth of palpation
(displacement of the sensors) and duration of the examination. An instrumented
breast model designed by the investigator provided quantitative measurements of
examination behaviors and was used to test outcomes of the instruction. RESULTS:
Multivariate analyses demonstrated an overall difference across examinations (F =
28.03; p = 0.0001). Univariate tests showed treatment effects for both dependent
variables: depth of palpation and duration of examination. CONCLUSIONS:
Individual training in BSE with guided practice improved two measures of
thoroughness of search: depth of palpation and duration of search time.
Biomedical instrumentation represented a novel approach to the collection of
quantitative performance data.
PMID- 11009124
TI - Nonlinear components of age-related change in sleep initiation.
AB - BACKGROUND: Although primary studies suggest that ability to initiate sleep
declines as people age, no systematic literature review has addressed the age(s)
at which adults experience the greatest change in their ability to initiate
sleep. OBJECTIVE: To explore whether there are any points in time across the
adult life span when the rate of change in ability to initiate sleep increases or
decreases. METHODS: Mathematical modeling was used to generate data points from
information about central tendency, variance, and correlations between age and
time to sleep onset provided by seven research reports. The reports represent 258
subjects ages 17 to 91 years. Smoothing splines were used to identify inflection
points suggestive of major changes in sleep initiation across the life span.
RESULTS: Two mathematical models were generated. One model suggested that
inflection points may exist around ages 30 and 50 years, respectively. With this
model, the amount of time until sleep onset increased until the age of 30 years,
but was unchanged from ages 30 to 50 years. Ability to initiate sleep appeared to
decline steadily after the age of 50 years. The second model, with a p value of
0.05, lacked adequate power to identify a significant nonlinear trend.
CONCLUSIONS: Decline in ability to initiate sleep may not occur at a steady rate
over the adult life span. Further research is needed to pinpoint thresholds of
change and possible gender differences in thresholds.
PMID- 11009125
TI - Methodologic issues associated with secretion weight as a dependent variable in
research using closed-system suction catheters.
AB - BACKGROUND: Closed-system suction catheters (CSSC) were designed to eliminate the
need to disconnect the patient from the ventilator during endotracheal suctioning
(ETS). During data collection on an NIH-funded study, it was noted that moisture
accumulated on the inside of the CSSC and sleeve when attached to the patient for
30 minutes. Because CSSC are not disconnected, they present unique methodologic
problems related to measurement of secretions as a dependent variable in clinical
research. OBJECTIVES: To describe a valid, reliable, and practical method for
weighing secretions obtained during ETS using a CSSC; and to determine the change
in weight of a CSSC after its attachment for 30 minutes to a mechanically
ventilated patient. METHODS: After being weighed, a CSSC and sputum trap were
attached to the endotracheal tube of a mechanically ventilated adult and remained
attached for 43 minutes (30 minutes to allow positive end expiratory pressure and
oxygenation levels to return to normal and 13 minutes to mimic the time frame for
the ETS procedure used in another study). No ETS occurred. The CSSC and sputum
trap were then removed and reweighed. RESULTS: A convenience sample consisted of
50 adults who were critically ill and mechanically ventilated. Independent
variables included tidal volume, pressure support, body temperature, and
respiratory rate. The dependent variable was wet weight of the CSSC, determined
by subtracting the preprotocol catheter weight from the postprotocol catheter
weight. The mean wet weight for all catheters was 0.5142 +/- 0.1215 grams. In a
subset of 37 patients, two wet weights (74 paired observations) were determined.
The mean wet weight for these catheters was 0.54014 +/- 0.1404 grams. The paired
wet weights were statistically different (t = 2.433; df = 36; p = 0.02). Pearson
correlation coefficients and beta coefficients were computed. While tidal volume
and pressure support were highly correlated (r = 0.678; p = 0.011), there were no
other statistically significant associations. CONCLUSIONS: The amount of
secretions is a common dependent variable in ETS research. During the time that
CSSC are attached to the patient and ventilator, moisture from either the
ventilator's humidification system or the patient accumulates in the CSSC. This
wet weight is not actually part of the secretions retrieved during ETS and should
not be considered in the actual weight of secretions. Further study on the
determinants of wet weight is warranted.
PMID- 11009126
TI - Application of the theory of gender and power to examine HIV-related exposures,
risk factors, and effective interventions for women.
AB - Developed by Robert Connell, the theory of gender and power is a social
structural theory based on existing philosophical writings of sexual inequality
and gender and power imbalance. According to the theory of gender and power,
there are three major social structures that characterize the gendered
relationships between men and women: the sexual division of labor, the sexual
division of power, and the structure of cathexis. The aim of this article is to
apply an extended version of the theory of gender and power to examine the
exposures, social/behavioral risk factors, and biological properties that
increase women's vulnerability for acquiring HIV. Subsequently, the authors
review several public health level HIV interventions aimed at reducing women's
HIV risk. Employing the theory of gender and power among women marshals new kinds
of data, asks new and broader questions with regard to women and their risk of
HIV, and, most important, creates new options for prevention.
PMID- 11009127
TI - New kinds of data, new options for HIV prevention among women: a public health
challenge.
PMID- 11009128
TI - Emergency department staff responses to a protocol of care for abused women.
AB - While there is increasing recognition by health care providers of the need to
identify and intervene in cases of partner abuse, there has been little
evaluation of the interventions that have been implemented. This article
documents emergency department staff responses to a five-step protocol of care on
partner abuse implemented in a public hospital. It draws on in-depth interviews
with a range of emergency department staff members, undertaken as part of the
project's process evaluation. Findings suggest protocol training provided staff
members with an opportunity to gain a greater awareness and understanding of
partner abuse. Protocol use improved and consolidated existing practices;
however, staff members were concerned about screening all women for abuse and
highlighted areas in which further support and resources are required. Taking
these factors into account may assist the appropriate and effective introduction
of such protocols in other health care settings.
PMID- 11009129
TI - A meta-analysis of fear appeals: implications for effective public health
campaigns.
AB - The fear appeal literature is examined in a comprehensive synthesis using meta
analytical techniques. The meta-analysis suggests that strong fear appeals
produce high levels of perceived severity and susceptibility, and are more
persuasive than low or weak fear appeals. The results also indicate that fear
appeals motivate adaptive danger control actions such as message acceptance and
maladaptive fear control actions such as defensive avoidance or reactance. It
appears that strong fear appeals and high-efficacy messages produce the greatest
behavior change, whereas strong fear appeals with low-efficacy messages produce
the greatest levels of defensive responses. Future directions and practical
implications are provided.
PMID- 11009130
TI - GO GIRLS!: results from a nutrition and physical activity program for low-income,
overweight African American adolescent females.
AB - This article describes the development, implementation, and results of an
intervention designed for inner-city, overweight African American adolescent
women. Fifty-seven participants were recruited from four public housing
developments. Participants were administered physiologic, dietary, and cognitive
assessments at baseline and immediately postintervention. Each session comprised
three elements: (1) an educational/behavioral activity, (2) 30 to 60 minutes of
physical activity, and (3) preparation and tasting of low-fat meals. In the
absence of a control group, results were compared for high and low attenders, the
former defined as attending at least 50% of the sessions. High attenders (n = 26)
showed more favorable 6-month posttest values for most outcomes compared with low
attenders (n = 31). These effects achieved statistical significance for nutrition
knowledge, low-fat practices, perceived changes in low-fat practices, and social
support.
PMID- 11009132
TI - The effect of the Maryland WIC 5-A-Day promotion program on participants' stages
of change for fruit and vegetable consumption.
AB - The Maryland Women, Infants and Children (WIC) 5-A-Day Promotion Program examined
the effect of a multifaceted nutrition intervention on changing the fruit and
vegetable consumption of low-income women in the WIC program in Maryland. The
sample consisted of 3,122 participants (1,443 intervention and 1,679 control)
with a mean age of 27.2. Fifty-six percent were Black/African American. This
article focuses on the effect of the intervention on the stages of change of the
participants. Intervention participants showed significantly greater positive
movement through the stages than control participants. Stages of change were
measured for two specific target behaviors: eating five servings of fruits and
vegetables a day and eating more servings of fruit and vegetables a day. Results
demonstrated significant differences in the stage status of intervention and
control women and in movement through the stages. The effectiveness of the
intervention across groups depended on which staging measure was used.
PMID- 11009131
TI - Dealing with diversity: recruiting churches and women for a randomized trial of
mammography promotion.
AB - There is little documentation about the recruitment process for church-based
health education programs. In this study, the authors recruit African American,
Latino, and white churches and women members (age 50 to 80) for a randomized
church-based trial of mammography promotion in Los Angeles County. Efforts to
enhance recruitment began 10 months before churches were invited to participate
and included a variety of community-based strategies. Subsequently, 45 churches
were recruited over a 5-month period through group pastor breakfast meetings and
church-specific follow-up. In close collaboration with the 45 churches, the
authors administered church-based surveys over 6 months and identified 1,967 age
eligible women who agreed to be contacted by the program team. It was found that
an extended resource intensive period of relationship-building and community
based activities were necessary to conduct church-based programs effectively,
particularly among older and ethnically diverse urban populations.
PMID- 11009133
TI - Enabling research in developing countries.
PMID- 11009134
TI - Development aid: manna or myth?
PMID- 11009135
TI - Can HIV-1 infections in Africa provide insights into acquired immunity to
malaria?
PMID- 11009137
TI - More rigour needed in trials of new diagnostic agents for tuberculosis.
PMID- 11009136
TI - A 21st century water cure.
PMID- 11009138
TI - Xenotransplantation: one trotter forward, one claw back.
PMID- 11009139
TI - Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and
clinical episodes in adults in rural Uganda: a cohort study.
AB - BACKGROUND: An association between HIV-1 and malaria is expected in theory, but
has not been convincingly shown in practice. We studied the effects of HIV-1
infection and advancing immunosuppression on falciparum parasitaemia and clinical
malaria. METHODS: HIV-1-positive and HIV-1-negative adults selected from a
population-based cohort in rural Uganda were invited to attend a clinic every 3
months (routine visits) and whenever they were sick (interim visits). At each
visit, information was collected on recent fever, body temperature, and malaria
parasites. Participants were assigned a clinical stage at each routine visit and
had regular CD4-cell measurements. FINDINGS: 484 participants made 7220 routine
clinic visits between 1990 and 1998. Parasitaemia was more common at visits by
HIV-1-positive individuals (328 of 2788 [11.8%] vs 231 of 3688 [6.3%], p<0.0001).
At HIV-1-positive visits, lower CD4-cell counts were associated with higher
parasite densities, compared with HIV-1-negative visits (p=0.0076). Clinical
malaria was significantly more common at HIV-1-positive visits (55 of 2788 [2.0%]
vs 26 of 3688 [0.7%], p=0.0003) and the odds of having clinical malaria increased
with falling CD4-cell count (p=0.0002) and advancing clinical stage (p=0.0024).
Participants made 3377 interim visits. The risk of clinical malaria was
significantly higher at visits by HIV-1-positive individuals than HIV-1-negative
individuals (4.0% vs 1.9%, p=0.009). The risk of clinical malaria tended to
increase with falling CD4-cell counts (p=0.052). INTERPRETATION: HIV-1 infection
is associated with an increased frequency of clinical malaria and parasitaemia.
This association tends to become more pronounced with advancing
immunosuppression, and could have important public-health implications for sub
Saharan Africa.
PMID- 11009140
TI - Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand:
a randomised trial.
AB - BACKGROUND: Some strains of scrub typhus in northern Thailand are poorly
responsive to standard antirickettsial drugs. We therefore did a masked,
randomised trial to compare rifampicin with standard doxycycline therapy for
patients with scrub typhus. METHODS: Adult patients with strictly defined, mild
scrub typhus were initially randomly assigned 1 week of daily oral treatment with
200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with
rifampicin (n=11). During the first year of treatment, the combined regimen was
withdrawn because of lack of efficacy and the regimen was replaced with 900 mg
rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the
time for oral temperature to fall below 37.3 degrees C). FINDINGS: About 12,800
fever patients were screened during the 3-year study to recruit 126 patients with
confirmed scrub typhus and no other infection, of whom 86 completed therapy.
Eight individuals received the combined regimen that was discontinued after 1
year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24
patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and
in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h)
than in the 28 patients given doxycycline monotherapy (fever clearance time 52
h). Fever resolved in a significantly higher proportion of patients within 48 h
of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in
patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe
gastrointestinal events warranted exclusion of two patients on doxycyline. There
were two relapses after doxycycline therapy, but none after rifampicin therapy.
INTERPRETATION: Rifampicin is more effective than doxycycline against scrub
typhus infections acquired in northern Thailand, where strains with reduced
susceptibility to antibiotics can occur.
PMID- 11009141
TI - Human herpesvirus 8 transmission from mother to child and between siblings in an
endemic population.
AB - BACKGROUND: Transmission of human herpesvirus 8 (HHV-8), the aetiological agent
of Kaposi's sarcoma, is known to occur during sex among homosexual men. However,
other modes of HHV-8 transmission remain to be elucidated in endemic populations.
METHODS: We did a population-based seroepidemiological survey in a village in
French Guiana among 1337 individuals of African origin (age 2-91 years) who had
reliable genealogical data. Plasma samples were taken and tested for HHV-specific
IgG by immunofluorescence assay. Risk factors and familial correlations for HHV-8
seropositivity were modelled by logistic regression analysis by use of the
estimating equations approach, which expresses familial dependences in terms of
odds ratios. Familial odds ratios were also acquired by use of the distribution
of all possible pairs of a given familial dependence. FINDINGS: The overall HHV-8
seroprevalence was 13.2% with no difference according to sex. HHV-8
seropositivity was strongly age dependent: at 1.2% under 5 years, HHV-8
seroprevalence rose up to a plateau around 15% between 15 and 40 years, and
showed a seroprevalence of more than 27% in individuals older than 40 years.
Strong familial aggregation in HHV-8 seroprevalence was found with high mother
child (odd ratio 2.8 [95% CI 1.6-5.0]) and sib-sib (3.8 [1.6-9.5]) correlations.
By contrast, no significant correlation between spouses (0.6 [0.2-1.9]) was seen.
INTERPRETATION: This pattern of familial aggregation, together with the variation
of HHV-8 seroprevalence with age, indicate that, in endemic populations, HHV-8
transmission mainly occurs from mother to child and between siblings during
childhood and adolescence.
PMID- 11009143
TI - The Krukenberg procedure: a surgical option for the treatment of double hand
amputees in Sierra Leone.
AB - BACKGROUND: For the past 9 years, Sierra Leone has struggled with a cruel civil
war in which the civilian population has been the principal target. The
International Committee of the Red Cross established a surgical mission in
Netland Hospital, Freetown, and during this surgical mission, we treated crippled
individuals who had had one or both hands amputated. We assessed the benefit of
the Krukenberg procedure to restore manual dexterity in this group. In this
operation, radius and ulna are separated and a pincer-like grasp is created.
METHODS: From July 15, 1998, to Sept 9, 1998, we carried out the Krukenberg
procedure on a group of double and single hand amputees. The main target group
was double hand amputees, however, the procedure was initially done on three
single hand amputees to assess the functional result. Between the original trauma
and the operation, there had been an interval of 3 months or longer in all
patients. Patients were followed up for 3 months after the procedure to assess
gripping strength and self-sufficiency (feeding, personal hygiene, dressing, and
manual dexterity). FINDINGS: 15 Krukenberg procedures were done on 11 patients:
eight men and three women (mean age 42 years). Three had single hand amputation
and eight had double hand amputation. In only two patients had sufficient time
passed for the stumps to heal. Of ten patients who were followed up at 3 months,
all could eat and drink by themselves. The simple dressing test was passed by all
patients and 75% of the patients had recovered some dexterity. INTERPRETATION:
The Krukenberg procedure is a surgical option to achieve some manual dexterity in
double hand amputees, where resources for sophisticated hand prostheses are
lacking.
PMID- 11009142
TI - Tuberculosis control and molecular epidemiology in a South African gold-mining
community.
AB - BACKGROUND: Gold miners have very high rates of tuberculosis. The contribution of
infections imported into mining communities versus transmission within them is
not known and has implications for control strategies. METHODS: We did a
prospective, population-based molecular and conventional epidemiological study of
pulmonary tuberculosis in a group of goldminers. Clusters were defined as groups
of patients with Mycobacterium tuberculosis isolates with identical IS6110 DNA
fingerprints. We compared the frequency of possible risk factors in the clustered
and non-clustered patients whose isolates had fingerprints with more than four
bands, and re-interviewed members of 45 clusters. FINDINGS: Of 448 patients, ten
were excluded because they had false-positive cultures. Fingerprints were made in
419 of 438, of which 371 had more than four bands. 248 of 371 were categorised
into 62 clusters. At least 50% of tuberculosis cases were due to transmission
within the community. Patients who had failed treatment at entry to the study
were more likely to be in clusters (adjusted odds ratio 3.41 [95% CI 1.25-9.27]).
Patients with multidrug-resistant isolates were more likely to have failed
treatment but were less likely to be clustered than those with a sensitive strain
(0.27 [0.09-0.83]). HIV infection was common (177 of 370 tested) but not
associated with clustering. INTERPRETATION: Despite a control programme that
cures 86% of new cases, most tuberculosis in this mining community is due to
ongoing transmission. Persistently infectious individuals who have previously
failed treatment may be responsible for one third of tuberculosis cases. WHO
targets for cure rates are not sufficient to interrupt transmission of
tuberculosis in this setting. Indicators that are more closely linked to the rate
of ongoing transmission are needed.
PMID- 11009144
TI - Talking to the patient.
PMID- 11009145
TI - Satellite mapping of Loa loa prevalence in relation to ivermectin use in west and
central Africa.
AB - For many years, ivermectin has been widely distributed throughout west Africa for
the safe and effective control of onchocerclasis. However, recent events in Loa
loa-endemic areas of Cameroon, where severe adverse reactions have occurred, now
constrain the public-health use of this drug in the forest habitat of the L. loa
vector. We have created a model of L. loa prevalence to identify areas where high
endemicity may be associated with the occurrence of such reactions. The model
results have been mapped and the areas of overlap between high L. loa prevalence
and planned ivermectin distribution for onchocerciasis control identified.
PMID- 11009146
TI - Carriage of serogroup W-135, ET-37 meningococci in The Gambia: implications for
immunisation policy?
AB - We found high levels of symptomless carriage of a hyperinvasive Neisseria
meningitidis strain (electrophoretic type 37 [ET-37], serogroup W-135) during a
vaccine trial in Gambian children in 1996. Serogroup C, ET-37 complex
meningococci cause 30-40% of meningococcal disease in countries such as the UK,
and have a point prevalence of 0.5-1.0%. The recent Haj-associated spread of
serogroup W-135, ET-37 complex meningococci, which has been accompanied by
numerous secondary cases, might be explained by the apparently raised carriage
rates reported here.
PMID- 11009147
TI - Rickettsia felis rickettsiosis in Yucatan.
AB - Three patients with fever, exanthem, headache, and central-nervous-system
involvement were diagnosed with Rickettsia fells infection by specific PCR of
blood or skin and seroconversion to surrogate Rickettsia antigens. Although R.
felis's relationship to other Rickettsia species is known and the pathogenic
potential of this clade is well documented, R. felis's role as a pathogen has not
been fully understood.
PMID- 11009148
TI - Chronic neuropathic pain in treated leprosy.
AB - The existence of chronic neuropathic pain in treated leprosy has received scant
attention. We describe the clinical findings of 16 patients with multibacillary
leprosy who had chronic stimulus-independent pain despite finishing their
treatment. With confirmation, our results could be of importance in the
establishment of "care after cure" programmes for patients with leprosy.
PMID- 11009149
TI - Duration of viraemia and faecal viral excretion in acute hepatitis E.
AB - Data on duration of viral excretion and viraemia during hepatitis E virus (HEV)
infection are limited. We tested serial stool and serum samples from 20 patients
with acute hepatitis E for HEV RNA. Faecal excretion and viraemia in these
patients were found to be short lived. In 19 patients, all samples obtained after
biochemical resolution of hepatitis tested negative; in the remaining patient,
HEV RNA was detected in the serum samples but not in stool after biochemical
resolution. Long-term persistence of HEV in body fluids of infected individuals
seems to be an unlikely reservoir for transmission of HEV.
PMID- 11009151
TI - Assessment of a 1-year teaching programme in Zanzibar, Tanzania.
AB - We assessed whether a 1-year teaching programme in northern Zanzibar would
improve prescribing practice. Data on polypharmacy and appropriateness of the
treatment of upper-respiratory infection, anaemia, and scabies from the 17
primary health-care units in northern Zanzibar were analysed before and after the
teaching programme. There was a significant and sustained reduction in
polypharmacy and an improvement in the treatment of upper-respiratory infection,
scabies, and anaemia. This teaching programme has been successful in improving
prescribing practices in a less-developed country.
PMID- 11009150
TI - Anthelminthic treatment and haemoglobin concentrations during pregnancy.
AB - A longitudinal study was conducted in Sierra Leone to measure the impact of a
single dose anthelminthic (400 mg albendazole) and daily iron-folate supplements
(36 g iron and 5 mg folate) on haemoglobin (HG) concentration during pregnancy.
After controlling for baseline Hb concentration and season, anthelmintic
treatment reduced the decline in haemoglobin concentration between the first and
third trimesters by 6.6 g/L (p=0.0034) relative to the control. The corresponding
value for iron-folate supplements was 13.7 g/L(p<0.0001) [corrected]. These
findings indicate that anthelminthic treatment should be included in strategies
to control maternal anaemia in Sierra Leone.
PMID- 11009152
TI - Women suffer first from lack of health-care services.
PMID- 11009153
TI - Single-dose treatment shows effectiveness for Indian visceral leishmaniasis.
PMID- 11009154
TI - The "gender gap" in autoimmune disease.
PMID- 11009155
TI - India steps up anti-tobacco measures.
PMID- 11009156
TI - More confusion about South African President's stance on HIV.
PMID- 11009157
TI - Concern about rise in AIDS in Romanian adults.
PMID- 11009158
TI - Anger at graphic evidence at Omagh inquest.
PMID- 11009159
TI - Explaining trends in inequities: evidence from Brazilian child health studies.
AB - There is considerable international concern that child-health inequities seem to
be getting worse between and within richer and poorer countries. The "inverse
equity hypothesis" is proposed to explain how such health inequities may get
worse, remain the same, or improve over time. We postulate that as new public
health interventions and programmes initially reach those of higher socioeconomic
status and only later affect the poor, there are early increases in inequity
ratios for coverage, morbidity, and mortality indicators. Inequities only improve
later when the rich have achieved new minimum achievable levels for morbidity and
mortality and the poor gain greater access to the interventions. The hypothesis
was examined using three epidemiological data sets for time trends in child
health inequities within Brazil. Time trends for inequity ratios for morbidity
and mortality, which were consistent with the hypothesis, showed both
improvements and deterioration over time, despite the indicators showing absolute
improvements in health status between rich and poor.
PMID- 11009160
TI - Specific immune-based diagnosis of tuberculosis.
AB - Current diagnostic tests for tuberculosis based on tuberculin have poor
specificity, and both BCG vaccination and exposure to non-tuberculosis
mycobacteria produce a response similar to that induced by infection with
Mycobacterium tuberculosis. The identification of regions of the M. tuberculosis
genome that are not present in BCG and non-tuberculous mycobacteria provides a
unique opportunity to develop new highly specific diagnostic reagents. We
describe the current status of attempts to exploit this information and summarise
recent research that has used defined antigens for an accurate and rapid test for
tuberculosis infection based on the detection of T cells sensitised to M.
tuberculosis either by blood tests in vitro or skin tests in vivo.
PMID- 11009161
TI - Evidence-based medicine--the view from Fiji.
PMID- 11009162
TI - Consequences of in-utero death in twin pregnancy.
PMID- 11009163
TI - Consequences of in-utero death in twin pregnancy.
PMID- 11009164
TI - Cardiovascular disease in South Asians.
PMID- 11009165
TI - Testing for West Nile virus.
PMID- 11009166
TI - Digital arterial occlusive disease.
PMID- 11009167
TI - Intra-arterial thrombolysis for hyperacute stroke.
PMID- 11009168
TI - Pumpless extracorporeal lung assist.
PMID- 11009169
TI - Breast carcinoma in young patients.
PMID- 11009170
TI - Breast carcinoma in young patients.
PMID- 11009171
TI - NICE and drugs for multiple sclerosis. National Institute of Clinical Excellence.
PMID- 11009172
TI - Jehovah's Witness blood policy.
PMID- 11009173
TI - Jehovah's Witness blood policy.
PMID- 11009174
TI - Jehovah's Witness blood policy.
PMID- 11009175
TI - Ethics of mass STD treatment.
PMID- 11009177
TI - On education and training.
PMID- 11009176
TI - Ethics of mass STD treatment.
PMID- 11009178
TI - Computational models of the basal ganglia.
AB - Computer simulation studies and mathematical analysis of models of the basal
ganglia are being used increasingly to explore theories of basal ganglia
function. We review the implications of these new models for a general
understanding of basal ganglia function in normal as well as in diseased brains.
The focus is on their functional similarities rather than on the details of
mathematical methodologies and simulation techniques. Most of the models suggest
a vital role for the basal ganglia in learning. Although this interest in
learning is partly driven by experimental results associating the acute firing of
dopamine cells with reward prediction in monkeys, some of the models have
preceded the electrophysiological results. Another common theme of the models is
selection. In this case, the striatum is seen as detecting and selecting cortical
contexts for access to basal ganglia output. Although the behavioral consequences
of this selection are hard to define, the models provide frameworks within which
to explore these ideas empirically. This provides a means of refining our
understanding of basal ganglia function and to consider dysfunction within the
new logical frameworks.
PMID- 11009180
TI - The pathogenesis of multiple system atrophy: past, present, and future.
AB - Multiple system atrophy is a sporadic, adult-onset neurodegenerative disease of
unknown etiology. The condition may be unique among neurodegenerative diseases by
the prominent, if not primary, role played by the oligodendroglial cell in the
pathogenetic process. Recent developments in our understanding of multiple system
atrophy have included the detection of glial cytoplasmic inclusions and alpha
synuclein accumulation in these inclusions. The latter finding links multiple
system atrophy as an "alpha-synucleinopathy" to Parkinson's disease and dementia
with Lewy bodies. This article reviews recent important findings of potential
relevance to the pathogenesis of multiple system atrophy. We also speculate on
areas in which further advances may be made to progress our understanding of this
devastating condition.
PMID- 11009179
TI - Neuropsychologic assessment of patients for movement disorder surgery.
AB - The neuropsychologic evaluation of patients under consideration for movement
disorder surgery is recognized as being an essential component of the
preoperative process. Patients with early-stage concomitant dementia must be
identified and the relative risk of postoperative cognitive decline evaluated.
Knowledge of the patterns of an individual's strengths and weaknesses might also
be a factor in deciding on a neurosurgical procedure. Although the advent of
pallidal deep brain stimulation (DBS) has possibly resulted in reduced risk of
induced cognitive impairment, even this procedure has been associated with
negative sequelae. DBS within the subthalamic nucleus is becoming the method of
choice and this may lead to cognitive and behavioral compromise, especially in
the elderly patient. The team considering the establishment of neurosurgical
treatment is often at a loss to decide how much neuropsychologic testing is
required to determine relative risks of cognitive or behavioral morbidity as a
consequence of the procedure. A brief summary of expected outcome and of
pertinent family process and psychodynamic issues are addressed. This article is
intended to serve as a guide to permit clinicians to choose the appropriate
length and depth of neuropsychologic assessment, but also to highlight the
confounding factors often present in these patients.
PMID- 11009181
TI - Apomorphine: an underutilized therapy for Parkinson's disease.
AB - Apomorphine was the first dopaminergic drug ever used to treat symptoms of
Parkinson's disease. While powerful antiparkinsonian effects had been observed as
early as 1951, the potential of treating fluctuating Parkinson's disease by
subcutaneous administration of apomorphine has only recently become the subject
of systematic study. A number of small scale clinical trials have unequivocally
shown that intermittent subcutaneous apomorphine injections produce
antiparkinsonian benefit close if not identical to that seen with levodopa and
that apomorphine rescue injections can reliably revert off-periods even in
patients with complex on-off motor swings. Continuous subcutaneous apomorphine
infusions can reduce daily off-time by more than 50% in this group of patients,
which appears to be a stronger effect than that generally seen with add-on
therapy with oral dopamine agonists or COMT inhibitors. Extended follow-up
studies of up to 8 years have demonstrated long-term persistence of apomorphine
efficacy. In addition, there is convincing clinical evidence that monotherapy
with continuous subcutaneous apomorphine infusions is associated with marked
reductions of preexisting levodopa-induced dyskinesias. The main side effects of
subcutaneous apomorphine treatment are related to cutaneous tolerability
problems, whereas sedation and psychiatric complications play a lesser role.
Given the marked degree of efficacy of subcutaneous apomorphine treatment in
fluctuating Parkinson's disease, this approach seems to deserve more widespread
clinical use.
PMID- 11009182
TI - Excitatory responses in the 'direct' striatonigral pathway: effect of
nigrostriatal lesion.
AB - The existence of a striatonigral GABAergic projection that inhibits substantia
nigra reticulata (SNr) cells has been well established. We report on
electrophysiological evidence in the rat for a striatonigral excitatory pathway
that affects 15% of all SNr cells. Using the antidromic response test to classify
SNr cells in relation to their projecting nucleus, an excitatory striatonigral
response was found in 57% of cells projecting to the pedunculopontine tegmental
nucleus (PPTg) and 11% of cells projecting to the thalamus. SNr cells innervated
by inhibitory or excitatory striatonigral inputs had a similar firing rate but a
lower variation coefficient (VC) than SNr cells that did not respond to
striatonigral inputs. The 6-hydroxydopamine (6-OHDA) degeneration of
nigrostriatal dopaminergic cells (A9) induced an increase in the percentage of
SNr cells excited from the striatum (52%) and in the VC, but no modification of
the firing rate or of the number of spikes induced by each striatal stimulus.
This increase in VC was found for the striatonigral inhibitory, but not for the
striatonigral excitatory pathway. These data indicate that in addition to its
inhibitory action, the direct striatonigral pathway has an excitatory activity
that is particularly prominent for SNr cells projecting to the pedunculopontine
nucleus. Because the percentage of SNr cells excited by this pathway was markedly
increased by DA cell degeneration, our findings suggest that the excitatory
striatonigral system could be involved in the pathophysiology of Parkinson's
disease.
PMID- 11009183
TI - Endogenous dopaminergic tone and dopamine agonist action.
AB - Dopamine receptor agonists provide symptomatic relief in the early stages of
Parkinson's disease, but with disease progression, their efficacy decreases. The
reason behind this decrease in effectiveness is unknown, but maximal efficacy may
be dependent on endogenous dopaminergic tone to provide stimulation of D1 and D2
receptor subtypes. Therefore, we have investigated the effects of the tyrosine
hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT) on the actions of D1, D2,
and D1/D2 agonists and levodopa (L-dopa) in common marmosets treated with 1
methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Administration of AMPT alone further
increased motor disability and decreased locomotor activity. Administration of L
dopa reversed motor disability and increased locomotor activity, and this
reversal was not affected by previous AMPT treatment. The D1 agonist A-77636 and
the D2 agonist quinpirole reversed motor deficits, but these effects were
markedly inhibited by previous AMPT treatment. Administration of quinpirole with
A-77636 produced a reversal of motor deficits that was more resistant to AMPT
pretreatment than was the effect produced by quinpirole or A-77636 alone. These
data suggest that D1 and D2 receptor stimulation are required for dopamine
receptor agonists to produce a maximal antiparkinsonian response. The reversal of
motor deficits produced by the mixed D1/D2 agonist apomorphine was more resistant
to AMPT treatment than that produced by quinpirole or A-77636. However, the motor
effects of A-77636 plus quinpirole and of apomorphine were still affected by AMPT
treatment. This suggests that loss of tyrosine hydroxylase activity may also
alter motor activity through inhibition of endogenous L-dopa or norepinephrine
synthesis, because both are also involved in the genesis of motor activity.
PMID- 11009184
TI - Alcohol dehydrogenase alleles in Parkinson's disease.
AB - Mutations in alcohol dehydrogenase (ADH; EC 1.1.1.1) genes may be of interest in
the etiology of Parkinson's disease (PD) because of the important role these
enzymes play in retinoid and dopamine metabolism and/or aldehyde detoxification.
The location of several alcohol dehydrogenase genes in a cluster on chromosome 4
lends further support to ADH genes being candidates for this disorder, because
recently a form of autosomal-dominant parkinsonism has been mapped to this area.
We sequenced the promoter and coding regions and part of the introns of the human
class IV ADH gene in 10 patients with PD. Seven different polymorphisms were
identified. These polymorphisms could be assigned to four alleles (A1-A4). We
then determined the frequencies of those four alleles and the wild-type allele in
78 patients with PD and 130 control subjects and found a significant association
of the A1 allele with PD (odds ratio = 2.87; 95% confidence interval = 1.35
6.08). In familial cases, the association was strongest (odds ratio = 4.86; 95%
confidence interval = 1.89-12.75). Two patients were homozygous for A1 whereas
none of the 130 control subjects was found to be homozygous. Our results show an
association between a certain ADH4 (formerly known as ADH7 in humans) allele and
PD. This suggests a role for genetic variations of ADH4 as risk factors for the
development of PD. Our data also show that the observed polymorphisms alone are
not sufficient to cause symptoms. Further genetic and/or environmental factors
have to be involved.
PMID- 11009185
TI - Influence of strict, intermediate, and broad diagnostic criteria on the age- and
sex-specific incidence of Parkinson's disease.
AB - We studied the influence of three sets of diagnostic criteria on the age- and sex
specific incidence of Parkinson's disease (PD) among residents of Olmsted County,
Minnesota, for the period 1976 to 1990. Incidence cases of parkinsonism were
detected using the medical records-linkage system of the Rochester Epidemiology
Project. PD was separated from other types of parkinsonism using strict,
intermediate, and broad criteria. We found 154 incident cases of PD using the
strict criteria, 215 using the intermediate criteria, and 266 using the broad
criteria. The incidence rate was consistently higher for men across all ages with
all three sets of criteria; however, sex differences were more striking at older
ages when using the broad criteria. In men above age 79 years, the incidence rate
of PD declined with strict criteria, remained stable with intermediate criteria,
and increased with broad criteria. The impact of diagnostic criteria on the age
specific incidence curve was less striking for women. When using the broad
criteria, the risk of PD increased constantly with age in both sexes, suggesting
that PD is an aging-related disease. Our findings suggest that the diagnostic
criteria used to separate PD from other types of parkinsonism influence the
magnitude of PD incidence and its distribution by age and sex.
PMID- 11009186
TI - Clinical problems in non-fluctuating patients with Parkinson's disease: a
community-based study.
AB - OBJECTIVE: To investigate the frequency of nonfluctuators in a community-based
prevalence study of Parkinson's disease (PD) and to describe disability, non
motor problems, and health-related quality of life in patients with PD with and
without motor fluctuations, and compare the findings to those of two control
groups. METHODS: The study involved 245 patients with PD who were participating
in a prevalence study and two control groups (100 healthy elderly individuals and
100 patients with diabetes mellitus [DM]). Data were obtained through neurologic
examination and a semistructured interview, and by the use of several
questionnaires. RESULTS: In this group of unselected patients with PD, 78% did
not experience motor fluctuations. Mean duration of treatment with levodopa was
6.3 years. Patients with motor fluctuations had a lower age at onset of disease,
longer duration of disease, and a higher daily levodopa dose than patients
without fluctuations. Among the non-fluctuating patients, we found more dementia
and a higher age at prevalence day. Disability (assessed by the Unified
Parkinson's Disease Rating Scale subscales for activities of daily living and
motor function and the Hoehn and Yahr stage) was similar in fluctuators and
nonfluctuators. Depression, sleep disturbances, and fatigue were equally frequent
in both patient groups. The occurrence of these difficulties was clearly more
frequent among non-fluctuating patients with PD than among the control subjects.
CONCLUSION: Most patients in the general population who have PD do not experience
dose-dependent motor fluctuations. Severity of motor disability and
neuropsychiatric manifestations are as important in non-fluctuators as in
fluctuators. Patients without motor fluctuations have more depression, sleep
disturbances, fatigue, and a poorer health-related quality of life than patients
with DM and healthy elderly individuals. This also underlines the importance of
developing better management and treatment strategies for this group of patients
with PD.
PMID- 11009187
TI - Decrease in presynaptic inhibition on heteronymous monosynaptic Ia terminals in
patients with Parkinson's disease.
AB - PURPOSE: Heteronymous Ia facilitation from the quadriceps to the soleus was
studied to clarify central motor control through presynaptic inhibition (PSI) on
Ia terminals of spinal motoneurons in Parkinson's disease. METHODS: 17 patients
with Parkinson's disease and 36 control subjects participated in the study.
Because the early part of facilitation reflects the degree of PSI, the extent of
facilitation was quantified as the slope, within 0.8 msec of onset. RESULTS:
Heteronymous Ia facilitation in the patients was greater than in the age-matched
control participants. PSI was negatively correlated with the walking speed of the
patients. In the patients examined twice, lessening of bradykinesia was
correlated to a decrease in PSI but not lessening of rigidity. CONCLUSION: These
findings indicate that the degree of PSI is decreased and disturbance of the
central control of PSI may relate to gait disturbance in Parkinson's disease.
PMID- 11009188
TI - Perseveration for novel stimuli in Parkinson's disease: an evaluation based on
event-related potentials topography.
AB - Event-related potential topography produced by novel and target stimuli was used
to detect dysfunction of mental switching (perseveration) in nondemented patients
with Parkinson's disease. The study participants were 15 patients with
Parkinson's disease and 13 age-matched healthy control patients. Ten percent of
the novelty tones with pitches of 125 and 500 Hz were added to 20% of the target
tones that had a pitch of 1000 Hz. Patients were instructed to count the target
tones. The modified Wisconsin Card Sorting Test was used to evaluate frontal lobe
function. Patients with Parkinson's disease showed a significant decrease in the
achieved categories and an increase in perseverative errors in the Wisconsin Card
Sorting Test. These results indicate that the cognitive impairment of patients
with Parkinson's disease can be characterized as failure of mental switching
related to frontal lobe dysfunction based on basal ganglia disturbance. As
compared with the control patients, patients with Parkinson's disease had shorter
P3 latencies to the novel stimuli and a more frontal distribution on the P3 map,
especially for the 125-Hz stimuli. This characteristic of P3 to novel stimuli in
the patients with Parkinson's disease, but not in the control patients, is
categorized by P3a (novelty P3). Our findings suggest that decreased mental
switching causes lack of novelty P3 habituation in patients with Parkinson's
disease and that it is related to learning disabilities based on dysfunction of
the frontal lobe and basal ganglia.
PMID- 11009189
TI - Determinants of tapping speed in normal control subjects and subjects with
Parkinson's disease: differing effects of brief and continued practice.
AB - BACKGROUND: Alternate tapping speed is widely used as a measure of bradykinesia
in Parkinson's disease (PD). Tapping speed in normal control subjects and factors
that might influence tapping speed have not been systematically examined.
OBJECTIVE: To examine the effects of age, hand dominance, and gender on tapping
speed in normal control subjects and to compare the effects of practice on
tapping speed in normal and PD control subjects. METHODS: Tapping speed for three
sequential trials in the dominant and nondominant hand was examined in 100 normal
control subjects and 60 subjects with PD. The effect of hourly practice over 26
hours (19 trials) was investigated in 14 normal and 24 PD subjects. RESULTS: The
speed with which normal subjects alternately tapped two counters was negatively
correlated with age, was greater in the dominant hand, was not related to gender,
and improved with short-term practice (three trials) and with continued practice
over 26 hours. Parkinsonian subjects, in general, tapped more slowly than normal
control subjects and more slowly in the more affected arm. Parkinsonian subjects
benefited from short-term practice as much as normal control subjects but, unlike
normal control subjects, did not improve with continued practice over 26 hours.
CONCLUSIONS: Alternate tapping speed is influenced by age, hand dominance,
Parkinson's disease, and practice. Subjects with PD do not benefit as much from
continued practice as do normal subjects, suggesting some limitation or
impairment of procedural (motor) learning in PD.
PMID- 11009190
TI - Lateral leg raising in patients with Parkinson's disease: influence of
equilibrium constraint.
AB - Patients with Parkinson's disease often have difficulty maintaining postural
stability. This impairment is attributed to postural adjustment deficits. We
studied the postural adjustments associated with the performance of two complex
tasks which differed only in the final equilibrium constraints. Ten patients with
Parkinson's disease and six age-matched control subjects were asked to raise one
leg laterally to an abduction angle of approximately 45 degrees as fast as
possible to the right or left in random order. In the first series of tests, the
subjects were instructed to maintain the leg at 45 degrees, whereas in the second
series they were instructed to place their foot back on the ground. Recordings
included ground reaction forces and kinematics. In the patients with Parkinson's
disease the final posture for the first task was never maintained. The strategy
used to shift the body weight was different for the two groups. In control
subjects, it was initiated by a whole body rotation around the ankle followed by
a trunk inclination around the hip. Conversely, in patients with Parkinson's
disease, the shift of the body weight was initiated by a trunk inclination around
the hip and then by a whole body rotation around the ankle. The amplitude of the
trunk inclination toward the supporting side was smaller than in the control
subjects. The second task with less severe equilibrium constraints was, on the
whole, better performed by the patients even though the same postural adjustment
deficits were present.
PMID- 11009191
TI - The effect of exercise on pharmacokinetics and pharmacodynamics of levodopa.
AB - The aim of our study was to evaluate the influence of low-intensity exercise on
levodopa absorption and levodopa motor effect. We studied the pharmacokinetics
and pharmacodynamics of levodopa under resting conditions and under a workload of
50 watts for 2 hours on a cycle ergometer in 12 parkinsonian patients with
predictable fluctuations of motor disability. The patients attended the hospital
on both days in a provoked off state. After a baseline assessment of motor
disability using the Columbia University rating scale (CURS scale) and a blood
test for measurement of the baseline levodopa concentration in the plasma, 100 mg
levodopa and 25 mg benserazide were administered as a single dose orally. Blood
samples for measurement of the levodopa concentration in the plasma were taken,
and motor assessments were conducted at 15-minute intervals for 240 minutes and
at 30-minute intervals from 240 to 360 minutes. All patients were able to perform
the exercise program. The baseline Columbia University rating scale score did not
differ significantly between both days. The mean levodopa concentration in plasma
at half-maximal motor effect tended to be higher during exercise and indicated
that the patients needed a higher levodopa concentration in plasma to achieve the
half-maximal motor effect. The maximal levodopa concentration in plasma tended to
be higher with exercise. Both trends did not reach statistical significance. In
summary, there was not a negative or a positive net effect of exercise on
pharmacokinetics and pharmacodynamics of levodopa. However, there were two
counteracting trends: a trend toward better levodopa absorption and a trend
toward a deteriorated concentration-effect correlation.
PMID- 11009192
TI - Pathologic gambling in Parkinson's disease: a behavioral manifestation of
pharmacologic treatment?
AB - We describe 12 patients with Parkinson's disease and pathologic gambling. This
association has apparently never been reported. The patients were selected from a
Parkinson's disease unit of 250 patients. They met Diagnostic and Statistical
Manual of Mental Disorders, 4th edition, criteria for pathologic gambling. All
patients underwent a neurologic, psychiatric, and psychologic examination,
specifically noting the presence or absence of psychopathology in the spectrum of
impulse control disorder and the nature of the gambling. Ten patients started
gambling after the onset of Parkinson's disease and treatment with levodopa. The
pathologic behavior was exclusively present or was markedly increased in "on"
periods in 11 patients. All patients had motor fluctuations at the time of the
study. Slot machines were the preferred source of gambling for 10 patients,
similar to the Spanish gambling population. That the gambling behavior appears
more often in the "on" periods of motor fluctuations and that it begins after the
onset of Parkinson's disease in most patients and worsens with levodopa therapy
suggest that it could be related to the dopaminergic tone in patients with
Parkinson's disease and motor fluctuations (that is, it could represent a
behavioral manifestation of pharmacologic treatment).
PMID- 11009193
TI - Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson's
disease.
AB - L-Dopa-induced dyskinesias constitute a challenge to the management of advanced
Parkinson's disease. According to recent reports, treatment with the NMDA
receptor antagonist amantadine may significantly diminish L-dopa-induced
dyskinesias. In the present study, the effect of amantadine on L-dopa-induced
dykinesias was assessed in a 5-week, double-blind crossover trial. Dyskinesia
severity as assessed following oral L-dopa challenges and by self-scoring
dyskinesia diaries were reduced approximately 50% after amantadine treatment
compared with baseline or placebo phases. Similarly, dyskinesia assessments on
the Unified Parkinson's Disease Rating Scale, part IV (items 32 and 33) also
revealed significant improvement after treatment with amantadine. The magnitude
of the L-dopa motor response to oral challenges was not different after
amantadine or placebo treatment, and there was no significant reduction of daily
off-time when patients received active treatment. These results confirm previous
observations concerning the antidyskinetic potential of amantadine.
PMID- 11009195
TI - An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous
exon 4 deletion in the parkin gene.
AB - We report the neuropathologic and genetic features of a 70-year-old man with
autosomal-recessive juvenile parkinsonism (AR-JP). At the age of 32 years, he
developed a dystonic gait, followed by hand tremor, rigidity, bradykinesia, and
impaired postural reflex. Levodopa was effective in ameliorating these symptoms.
Pathologic examination of autopsy specimens from this patient revealed loss of
pigmented neurons and gliosis in the substantia nigra pars compacta (SNPC), being
most pronounced in the medial and ventrolateral regions, and locus ceruleus (LC).
The melanin content of the remaining SNPC neurons was low. This feature was less
marked in the LC. There were no Lewy bodies, as confirmed by immunostaining for
alpha-synuclein. An additional, significant finding in this patient was neuronal
loss and fibrillary gliosis in the substantia nigra pars reticulata; this feature
has not been reported previously in AR-JP. Gene analysis revealed that this
autopsied patient and his siblings had the parkin gene mutation (homozygous exon
4 deletion) that is responsible for the disease.
PMID- 11009194
TI - The role of sensory cues in the rehabilitation of parkinsonian patients: a
comparison of two physical therapy protocols.
AB - We devised a single-blind study to assess the role of providing external sensory
cues in the rehabilitation of patients with idiopathic Parkinson's disease (PD).
Twenty stable, nondemented patients with PD entered a 6-week rehabilitation
program and were randomly assigned to two balanced protocols which were
differentiated by the use of external sensory cues ("non-cued" vs "cued").
Patients were evaluated by a neurologist, who was blind to group membership, with
the Unified Parkinson's Disease Rating Scale (UPDRS) at baseline, end of
treatment, and after 6 weeks. Patient groups were comparable for age, disease
duration, and severity. A significant reduction of UPDRS scores (activities of
daily living and motor sections) was present after the rehabilitation phase in
both groups. However, at follow up, while this clinical improvement had largely
faded in the "non-cued" group, mean UPDRS scores of the "cued" group were still
significantly lower than baseline values. The incorporation of external sensory
cues in the rehabilitation protocol can extend the short-term benefit of physical
therapy in moderately disabled patients with PD, possibly as a result of the
learning of new motor strategies. "Cued" physical therapy for PD should be
targeted to compensate for the defective physiological mechanisms.
PMID- 11009196
TI - Deficit of brain and skeletal muscle bioenergetics in progressive supranuclear
palsy shown in vivo by phosphorus magnetic resonance spectroscopy.
AB - Brain and muscle energy metabolism was assessed in vivo in five patients with
progressive supranuclear palsy (PSP) using phosphorous magnetic resonance
spectroscopy (31P MRS). 31P MRS disclosed a reduced phosphocreatine (PCr) and an
increased calculated free adenosine diphosphate (ADP) in the occipital lobes of
all patients. In our patients with PSP, inorganic phosphate (Pi) was
significantly increased and Mg2+ was reduced. In the gastrocnemius muscle, Pi at
rest was increased in four patients, and the three patients who were able to
perform an incremental exercise showed a rate of PCr postexercise recovery slower
than control subjects. Our findings show that multisystemic deficit of energy
metabolism occurs in PSP and suggest that it may play a role in the pathogenesis
of this disorder.
PMID- 11009198
TI - Dysarthria and orofacial apraxia in corticobasal degeneration.
AB - The authors evaluated dysarthria and orofacial apraxia (OFA) in 10 patients with
a clinical diagnosis of corticobasal degeneration (CBD). Nine patients were
slightly dysarthric according to the French version of the Frenchay Dysarthria
Assessment, which evaluates the motricity of the components of the vocal tract.
The severity of dysarthria assessed by an intelligibility score was correlated to
the global severity of the disease, but not to the duration of the disease.
Voluntary movements of the tongue and the lips were impaired in all patients.
OFA, evaluated with simple and sequential gestures, was present in nine patients.
Sequential gestures were more frequently impaired. The score of OFA was not
correlated to the severity of dysarthria, suggesting independent underlying
mechanisms. Thus, when specifically assessed, dysarthria and OFA are more
frequent in CBD than usually reported. We propose that the underlying
pathophysiology is the result of a deficit in programming and execution of
repetitive movements.
PMID- 11009197
TI - Voxel-based distribution of metabolic impairment in corticobasal degeneration.
AB - This report emphasizes the precise topographic distribution of cerebral metabolic
impairment in corticobasal degeneration (CBD) and the pathophysiological
differences between CBD and progressive supranuclear palsy (PSP). Statistical
parametric mapping (SPM96) analysis of 18FDG positron emission tomography (PET)
data was performed in 22 patients with CBD compared with 46 healthy subjects (HS)
and 21 patients with PSP who were studied at rest. A statistical threshold of p
<0.001 was fixed, further corrected for multiple or independent comparisons (p
<0.05). In comparison with HS, the metabolic impairment in CBD was asymmetrically
distributed in the putamen, thalamus, precentral (Brodmann's area, BA 4), lateral
premotor (BA 6/44) and supplementary motor areas (SMA, BA 6), dorsolateral
prefrontal (8/9/46) cortex, and the anterior part of the inferior parietal lobe
(BA 40) including the intraparietal sulcus (BA 7/40). A similar hypometabolic
pattern was observed for most individual analyses. When PSP was compared with
CBD, metabolic impairment predominated in the midbrain, anterior cingulate (BA
24/32), and orbitofrontal regions (BA 10). The reverse contrast showed more
posterior involvement in CBD (BA 6 and 5/7/40) including SMA. Our data suggest
that multiple components of neural networks related to both movement execution
and production of skilled movements are functionally disturbed in CBD compared
with both HS and PSP.
PMID- 11009199
TI - Thalamic tremor: correlations with three-dimensional magnetic resonance imaging
data and pathophysiological mechanisms.
AB - Tremor associated with a single focal thalamic lesion has rarely been reported.
Furthermore, the exact localization of the lesions is difficult to determine
because of the imprecision of "conventional" radiology (computed tomography scan
and/or "standard" magnetic resonance imaging). The aim of this study was to
identify which thalamic structures are involved in tremor associated with a
single focal thalamic lesion. We selected two patients who presented with
unilateral postural and kinetic tremor of the upper limb related to a localized
thalamic infarction. Three-dimensional T1-weighted magnetic resonance imaging
sequence (MP-RAGE sequence) was used to determine the precise topography of the
lesions by stereotactic analysis using the atlas of Hassler. The lesions were
located within the pulvinar, the sensory nuclei, the mediodorsal nucleus, and the
ventral lateral posterior nucleus (according to the classification of Hirai and
Jones), the latter including the ventral intermediate nucleus (Vim according to
the classification of Hassler). However, the Vim was spared. The subthalamic
area, which can induce tremor, was not involved. After having compared the
topography of the lesions with the clinical findings, we suggest that thalamic
tremors may result from the interruption of the cerebellar outflow tract to the
Vim within the thalamus.
PMID- 11009200
TI - Irregular jerky tremor, myoclonus, and thalamus: a study using low-frequency
stimulation.
AB - High-frequency thalamic stimulation alleviates tremor in Parkinson's disease (PD)
and essential tremor (ET). The origin of thalamic myoclonus is unexplained and
the effects of low-frequency thalamic stimulation on movement control are still
unknown. We studied the effects of stimulation at a low frequency of 15 Hz in
five drug-free patients (3 PD, 2 ET) 6 months after thalamic implantation of
quadripolar electrodes (unilateral in four patients, bilateral in one patient).
Clinical, electrophysiological, and videotaped assessment, using a monopolar 15
Hz frequency (3 V, 90 micros) stimulation current applied simultaneously through
two adjacent contacts of the electrode, was performed. We observed myoclonus and
irregular jerky tremor in the upper limb contralateral to the site of
stimulation. The jerks lasted less than 200 ms, were irregular and not
synchronous with stimulation, were superimposed on rest or postural tremor, and
increased in response to tactile, proprioceptive, or vibratory stimuli. The fact
that this complex movement disorder can be induced by low-frequency stimulation
in the ventral intermediate nucleus (Vim) of the thalamus suggests that it
results, at least partly, from dysfunction of the Vim and possibly adjacent
nuclei of the thalamus.
PMID- 11009201
TI - Environmental stimulation increases survival in mice transgenic for exon 1 of the
Huntington's disease gene.
AB - Mice transgenic for the first exon of the human Huntington's disease (HD) gene
carrying an expanded CAG repeat expansion (R6/2 line) develop a progressive
neurologic phenotype with symptoms resembling those seen in HD. The overt
symptoms of R6/2 mice worsen with age, resulting in a rapid decline in health and
premature death between 13 and 18 weeks of age. In this study, we characterized
the onset and progression of the overt phenotype in R6/2 mice and examined
factors that affect the phenotype and life expectancy of these mice. In
particular, the effects of altering home cage environment, through changing
feeding regimes and providing environmental stimulation, were investigated. We
show that changes in feeding regimes significantly improved the general well
being and life expectancy of R6/2 mice. Furthermore, we find that various forms
of environmental stimulation, including regular behavioral testing, significantly
improved the survival of R6/2 mice over and above that resulting from the
enhanced feeding regime. The fact that environmental stimulation improves the
health and life expectancy in R6/2 mice not only enables the mice to serve as
more useful research tools, but also suggests that environmental stimulation may
have a beneficial impact on the progression of HD in patients.
PMID- 11009202
TI - Spinal and cortical inhibition in Huntington's chorea.
AB - In this article we studied spinal and cortical inhibitory mechanisms in patients
with Huntington's disease. To evaluate spinal cord inhibitory circuitries, we
assessed reciprocal inhibition between antagonist forearm muscles and the
recovery cycle of the H reflex in the flexor carpi radialis. Patients showed a
significant decrease in the presynaptic phase of reciprocal inhibition reaching a
minimum at the conditioning-test interval of 20 msec and an abnormal facilitation
of the test H reflex at the conditioning test interval of 40 to 60 msec.
Throughout its time course (10-200 msec), the H reflex recovery cycle showed a
more prominent facilitation in patients than in control subjects. To assess
whether the observed pathophysiological abnormalities might have arisen from an
abnormal motor cortical excitability, we examined the recovery cycle of the motor
potentials evoked by paired transcranial magnetic stimuli. We found that the
inhibitory mechanisms controlling motor cortical excitability were normal. An
interpretation of the spinal cord abnormalities is that the intrinsically normal
but deafferentated motor cortex in Huntington's disease partly loses its
inhibitory control, thus disinhibiting spinal cord circuitry. Our findings from
paired transcranial magnetic stimulation suggest that cortical motor areas are
not hyperexcitable in Huntington's disease. Hence, the postulated thalamocortical
overactivity in experimental models of Huntington's disease needs to be
reappraised.
PMID- 11009203
TI - Pallido-Luysio-Nigral atrophy revealed by rapidly progressive hemidystonia: a
clinical, radiologic, functional, and neuropathologic study.
AB - Pallido-luysio-nigral atrophy (PLNA) is a rare neurodegenerative disease in which
the clinical and radiologic correlates have not yet been clearly established. A
62-year-old man insidiously developed dystonic postures, choreoathetoid
movements, slowness, and stiffness, which initially affected the right hand and
foot and progressively spread to the entire right side. T2-weighted magnetic
resonance imaging showed increased signal intensity in both left and right medial
pallida and in the left substantia nigra. Tests using HMPAO-SPECT and FDG-PET
demonstrated left cortical hyperperfusion and hypermetabolism, whereas the left
lenticular nucleus was slightly hypometabolic. At age 65, abnormal movements and
postures involved all four limbs and the axis causing major gait disturbances,
and facial and bulbar muscles atrophied resulting in dysarthria, dysphagia, and
impaired breathing. Diffuse amyotrophy and fasciculations also appeared. Death
occurred at age 66, 4 years after onset. At autopsy, severe bilateral neuronal
loss and gliosis restricted to the pallidum, the subthalamic nucleus, the
substantia nigra, and the hypoglossal nucleus were noted, accounting for the
diagnosis of PLNA with lower motor neuron involvement. Progressive hemidystonia
with adult onset represents an unusual clinical presentation for this disorder.
Moreover, this observation indicates that a diagnosis of PLNA should be
considered for specific magnetic resonance imaging, SPECT, and/or PET data, and
suggests that in PLNA, pallidal dysfunction might play a key role in the dystonic
presentation.
PMID- 11009205
TI - Quantification of sensory trick impact on tremor amplitude and frequency in 60
patients with head tremor.
AB - Head tremor with an obvious head deviation is the typical clinical picture of
tremulous cervical dystonia (TCD), whereas head tremor without any significant
head deviation allows for the differential diagnosis of dystonic head tremor
(DHT) as well as essential head tremor (EHT). Clinical and polyelectromyographic
(poly-EMG) studies have shown a suppression of dystonic muscle activity in
patients with TCD performing a maneuver called geste antagonistique. The effect
of these trick maneuvers on head tremor has not been investigated in patients
with DHT and EHT. We studied the impact of sensory trick maneuvers on head tremor
amplitude and frequency clinically by using the tremor subscore of the Tsui scale
and by means of computer-based accelerometry in 60 patients with head tremor as
their major disorder. Based on clinical data (modified Tsui scale: rating of
spontaneous head deviation [rotation + lateroflexion + ante-/retroflexion]),
pharmacologic response of tremor (propranolol, primidone, or alcohol), family
history (postural hand tremor in first-degree relatives), and poly-EMG findings
(reciprocal inhibition in neck muscles during voluntary head rotation), 34
patients were diagnosed as having TCD, 14 were classified as having DHT, and 12
patients were diagnosed as having EHT. Using a clinical rating scale, head tremor
amplitudes showed a significant decrease compared with baseline during the
performance of sensory trick maneuvers in patients with TCD and DHT, but not in
patients with EHT. This clinically observed effect was accompanied by a
significant reduction in the mean peak power of the dominant frequency in
patients with TCD (decrease by 83%, p = 0.0001) and DHT (decrease by 90%, p =
0.01), but not in patients with EHT (decrease by 6%, p = 0.6). Head tremor
frequencies showed no significant changes in relation to the trick maneuvers. We
conclude that a significant reduction of head tremor amplitude during a sensory
trick maneuver is a useful quantitative criterion to distinguish TCD and DHT from
EHT.
PMID- 11009204
TI - A Yorkshire family with adult-onset cranio-cervical primary torsion dystonia.
AB - Although a family history is described in approximately 20% of patients, large
families with adult-onset craniocervical primary (idiopathic) torsion dystonia
(PTD) are rare. We report a new British family with cranio-cervical dystonia.
Seventeen members of the family were examined. Five cases were diagnosed as
definite PTD and one as probable PTD. Mean age at onset was 29 years (range, 19
40 yrs). The phenotype was characterized by adult-onset cranio-cervical dystonia
in all affected cases. A few cases had additional voice tremor and/or postural
arm tremor. The GAG deletion in the DYT1 gene was excluded in the index case.
Linkage analysis was performed between the disease and several marker loci
spanning DYT6 and DYT7 regions, and haplotypes were reconstructed in all
subjects. Although linkage analysis was not completely informative, reconstructed
haplotypes excluded linkage between the disease and either DYT6 or DYT7. This
report confirms that familial cranio-cervical dystonia is genetically
heterogeneous, and further studies of other PTD families with similar clinical
features are needed to identify other new genes.
PMID- 11009206
TI - Disturbed sensorimotor processing during control of precision grip in patients
with writer's cramp.
AB - The aim of the study was to investigate force regulation in patients with
writer's cramp when performing a drawer-opening task using the precision grip.
Experimental conditions included intervening load pulses and vibratory
manipulations for examining grip force responses to sensory disturbances. The
data revealed that grip force was increased in patients with writer's cramp
compared with normal subjects, with a stronger modulation in the symptomatic
compared with the asymptomatic hand. This denotes a change in force scaling
capabilities and most notably for the preferred hand used in manipulative
activities. Vibratory stimulation of the extrinsic hand/finger muscles resulted
in an increased grip force of both hands in the patients with writer's cramp. The
latter was not observed in normal subjects and supports a bilateral dysfunction
in sensorimotor integration resulting from focal dystonia. In conclusion, the
disturbed regulation of the precision grip during a drawer-opening task is
illustrative for the inability of patients with writer's cramp to efficiently
control the force output during manipulative activities.
PMID- 11009207
TI - Botulinum toxin antibody testing: comparison between the mouse protection assay
and the mouse lethality assay.
AB - Conventionally, the standard test for detection of antibodies against botulinum
toxin (BT-A) has been the mouse lethality assay (MLA). Because this test has a
number of disadvantages, a novel mouse protection assay (MPA) was recently
introduced. We sought to compare the results of both tests. Forty-three samples
from 38 patients with cervical dystonia and complete or partial subjective BT-A
therapy failure underwent simultaneous MPA and MLA testing. Twenty-seven samples
showed concordant results in both tests. Eleven of them were MPA- and MLA
positive and 16 MPA- and MLA-negative, resulting in a significant association of
the dichotomous test results (Fisher exact test, p <0.01). Sixteen samples showed
discordant results. All of those were MPA-positive and MLA-negative. This excess
of MPA-positive results was also significant (Wilcoxon signed-rank test, p
<0.001). Of the patients with MPA-positive samples, 62% had complete and 38% had
partial therapy failure. Of the patients with MLA-positive samples, 90% had
complete and 10% had partial therapy failure. MPA and MLA results show
significant association. Statistical analysis and predominance of partial therapy
failure in MPA-positive patients demonstrate higher sensitivity of MPA. With its
methodologic advantages, its test parameter being more relevant to BT-A therapy,
and its higher sensitivity, the MPA appears to be superior to the MLA.
PMID- 11009208
TI - Isolation and 13C-NMR characterization of an insoluble proteinaceous fraction
from substantia nigra of patients with Parkinson's disease.
AB - Neuromelanin is a dark brown pigment suspected of being involved in the
pathogenesis of Parkinson's disease. This pigment can be isolated from normal
human substantia nigra by a procedure that includes an extensive proteolytic
treatment. In this study we used such a procedure to extract the neuromelanin
pigment from a pool of substantia nigra from patients affected by Parkinson's
disease. 13C Cross polarization magic angle spinning nuclear magnetic resonance
spectroscopy and electron paramagnetic resonance spectroscopy were used to
characterize the solid residue obtained from the extraction procedure. We found
that the pigment extracted from the substantia nigra of parkinsonian patients was
mainly composed of highly cross-linked, protease-resistant, lipo-proteic
material, whereas the neuromelanin macromolecule appears to be only a minor
component of this extract. A synthetic model of melanoprotein has been prepared
by enzymatic oxidation of dopamine in the presence of albumin. Once it has
undergone the same proteolytic treatment, this model system yields a 13C-NMR
spectrum which is similar to that observed for the parkinsonian midbrain extract.
These results are consistent with the view that oxidative stress has a relevant
role in the pathogenesis of Parkinson's disease.
PMID- 11009209
TI - Increased blink rate in advanced Parkinson's disease: a form of 'off'-period
dystonia?
AB - Blink rates were measured in 25 patients with fluctuating Parkinson's disease in
the "off' and "on" periods. In 17 patients, the "off"-period blink rate was low
and increased after administration of levodopa. In the remaining eight patients,
the "off"-period blink rate was high and returned to normal levels after
levodopa. It is suggested that increased blink rate in the latter group
represents a new form of "off"-period dystonia.
PMID- 11009210
TI - Tolerability of paroxetine in Parkinson's disease: a prospective study.
AB - Depression is a common finding in patients with Parkinson's disease (PD).
Traditionally, depression has been treated with tricyclic antidepressants, which
are often associated with undesirable side effects that may limit their use in
PD. Few studies have been performed with selective serotonin reuptake inhibitors
(SSRIs) in these patients. We assessed the tolerability of the SSRI
antidepressant paroxetine (10-20 mg once per day) in 65 outpatients with PD and
depression for a period of at least 3 months. Treatment was continued for 125.3+/
89.6 days (mean +/- standard deviation) in 52 patients. In these subjects the
Hamilton Disease Rating Scale improved from 21.7+/-6.4 to 13.8+/-5.8 (p <0.001).
Overall, 13 patients stopped paroxetine after 9.6+/-10.6 days because of adverse
reactions. Two patients reported increased "off" time and tremor that reversed
after treatment was stopped. No risk factors for intolerance were identified.
Paroxetine is a safe and effective drug to treat depression in PD.
PMID- 11009211
TI - Neuronal intranuclear inclusion disease and juvenile parkinsonism.
AB - Juvenile parkinsonism (onset age <20 yrs) is uncommon and few cases with
neuropathologic confirmation have been reported. We present the case of a 17-year
old boy who presented with asymmetric arm tremor and bulbar symptoms. His
paternal great aunt had parkinsonism with onset at age 22 years. Examination
revealed parkinsonism in the absence of additional neurologic signs except for
delayed pupillary responses to light. He responded well to levodopa but developed
motor fluctuations and disabling dyskinesias after 3 years of treatment.
Following attempted withdrawal of levodopa at age 24 years, he developed severe
aspiration pneumonia complicated by cardiorepiratory arrests and he died 6 months
later. At autopsy, the dominant histologic feature was wide-spread neuronal
hyaline intranuclear inclusions. Neuronal depletion was observed in the
substantia nigra, locus ceruleus, and, to a lesser extent, in the frontal cortex,
and inclusions were particularly prominent in these areas. Inclusions were
immunoreactive for ubiquitin and were typical of those seen in neuronal
intranuclear inclusion disease (NIID), a rare, multisytem neurodegenerative
disease. NIID should be considered in the differential diagnosis of juvenile
parkinsonism. A link between NIID and hereditary neurodegenerative disorders
characterized by expanded polyglutamine tracts is supported by the similar
appearance of intranuclear inclusions in both conditions and by a family history
in some cases of NIID.
PMID- 11009212
TI - The first identified French family with dentatorubral-pallidoluysian atrophy.
AB - We report the first French family with dentatorubral-pallidoluysian atrophy
(DRPLA) in which three members, a 36-year-old woman (proband), her 34-year-old
sister, and 14-year-old brother were affected. There was no family history of
DRPLA and their father presented at age 66 with pes cavus but without any other
neurologic symptoms. Molecular analysis of the DRPLA gene from blood leukocytes
showed CAG repeat sizes to be 68/16 in the proband, 62/15 in her father, and
16/16 in her mother. This study provides support for the variable clinical
presentation of this disease with incomplete penetrance in the father and
demonstrates that DRPLA can be observed in the French Caucasian population.
PMID- 11009213
TI - Exploration of motor cortex excitability in a diabetic patient with hemiballism
hemichorea.
AB - Hemiballism-hemichorea in older patients with hyperglycemia, associated with high
signal intensity in the contralateral striatum on T1-weighted magnetic resonance
scans, is now an accepted clinical entity. We present an additional patient with
this disorder. Using transcranial magnetic stimulation, we show that
intracortical inhibition in the motor cortex contralateral to hemiballism
hemichorea is increased. This finding is discussed in the context of current
models of basal ganglia-thalamo-cortical connectivity.
PMID- 11009214
TI - Progressive multifocal leukoencephalopathy presenting with an isolated focal
movement disorder.
AB - Progressive multifocal leukoencephalopathy (PML) is a rare but fatal papovavirus
infection of the central nervous system predominantly affecting immunocompromised
patients. Although the basal ganglia circuitry may be involved in the pathology
of PML, movement disorders are exceedingly rare as presenting symptoms and have
not been described as isolated features in such patients. We report a previously
healthy, immunocompetent 24-year-old woman with histologically proven PML who
presented with a focal movement disorder of the left arm as an isolated symptom
for many months before diagnosis.
PMID- 11009216
TI - Meta-analysis of polymorphism of the catechol-O-methyltransferase gene in
relation to the etiology of Parkinson's disease in Japan.
PMID- 11009215
TI - Life-threatening dystonia-dyskinesias in a child: successful treatment with
bilateral pallidal stimulation.
AB - We report a 13-year-old boy who developed severe, refractory dystonia-dyskinesias
as an abrupt worsening of a previously nonprogressive movement disorder. The
movements became continuous, requiring artificial respiration and continuous
sedation in the intensive-care unit. Various drugs and drug combinations failed
to achieve control. The child was then treated successfully with bilateral
pallidal (GPi) stimulation as shown in the videotape. Four months later and
without medication, the boy regained autonomous gait and audible speech; his
neurologic condition continues to improve.
PMID- 11009217
TI - Is there addiction to levodopa in patients with Parkinson's disease?
PMID- 11009218
TI - The use of NMDA antagonist memantine in drug-resistant dyskinesias resulting from
L-dopa.
PMID- 11009219
TI - Cerebrotendinous xanthomatosis with predominant parkinsonian syndrome: further
confirmation of the clinical heterogeneity.
PMID- 11009220
TI - Clinical and genetic study of familial essential tremor in an isolate of Northern
Tajikistan.
PMID- 11009221
TI - Bilateral striatal necrosis associated with Mycoplasma pneumoniae infection in an
adolescent: clinical and neuroradiologic follow up.
PMID- 11009222
TI - Jaw-opening dystonia presumably caused by a pontine lesion.
PMID- 11009223
TI - Eyelid dystonia in Machado-Joseph disease.
PMID- 11009224
TI - Choreic movements induced by cibenzoline: an Ic class antiarrhythmic effect?
PMID- 11009225
TI - Parkinsonism in HIV encephalopathy.
PMID- 11009226
TI - Reversing tissue injury-induced plastic changes in the spinal cord: the search
for the magic bullet.
PMID- 11009227
TI - Introduction: Gaston Labat Award 2000--Gary R. Strichartz, Ph.D.
PMID- 11009228
TI - Pathways and obstacles to local anesthesia, a personal account: the 2000 Gaston
Labat lecture.
PMID- 11009229
TI - Effect of oral ketamine on secondary hyperalgesia, thermal and mechanical pain
thresholds, and sedation in humans.
AB - BACKGROUND AND OBJECTIVES: Ketamine is an N-methyl-D-aspartate (NMDA) receptor
antagonist, and has been proven effective in alleviating secondary hyperalgesia
in human subjects when injected intravenously. After oral ingestion, ketamine is
metabolized into norketamine, which in vitro possesses NMDA receptor antagonistic
effect. The aim of this study was to investigate the effects of oral
administration of ketamine on secondary hyperalgesia evoked by standardized
tissue injury. METHODS: Twenty-four male volunteers were included in the study.
Each volunteer received the following treatment regimen, in randomized, double
blind, 3-way cross-over fashion: (A) placebo; (B) ketamine, 0.5 mg/kg; and (C)
ketamine, 1.0 mg/kg. Standardized tissue injury was induced after study
medication by heating the right calf with a rectangular thermode. The temperature
was 47 degrees C, and heating time was 7 minutes. The following parameters were
investigated: Pain during induction of the burn injury; heat-pain detection
thresholds in the injured area and a corresponding noninjured area; secondary
hyperalgesia surrounding the injured area on the calf; secondary hyperalgesia
induced by heating an area on the thigh with 45 degrees C in 3 minutes; pressure
pain detection thresholds measured on the middle phalanx of the 4th left finger;
pain during a 60-second thermal stimulation of 46 degrees C on undamaged skin on
the left thigh; and side effects. RESULTS: Some degree of sedation was observed
after oral administration of ketamine. No effects on any of the other
investigated parameters were observed. CONCLUSION: Oral ketamine 0.5 or 1.0 mg/kg
has no effect on secondary hyperalgesia or thermal or mechanical pain thresholds
in human volunteers.
PMID- 11009230
TI - Efficacy of oral mexiletine for neuropathic pain with allodynia: a double-blind,
placebo-controlled, crossover study.
AB - BACKGROUND AND OBJECTIVES: Mexiletine is an oral sodium channel antagonist that
has been reported to be effective in a variety of neuropathic pain syndromes.
However, recent reports question the efficacy of oral mexiletine in neuropathic
pain. The objectives of this study were to examine the effect of oral mexiletine
on pain, neurosensation, allodynia, and quality of life. METHODS: Twenty subjects
suffering from neuropathic pain with prominent allodynia were enrolled in a
randomized placebo-controlled crossover study. Patients were titrated to a
maximum dose of 900 mg/d or dose-limiting side effects, whichever occurred first.
At baseline and on days 0, 4, 7, and 10, the following tests were performed: (1)
Quality of Life Questionnaires; (2) pain scores; (3) area of allodynia; (4) side
effects; (5) neurosensory testing; and (6) peak and trough plasma mexiletine
levels. RESULTS: Peak plasma levels occurred on day 10 and were 0.54 microg/mL.
There was no significant effect on any quality of life measurement. There was no
significant effect on any neurosensory threshold or the area of allodynia. There
was a significant effect of mexiletine on stroking-induced pain. There were no
significant effects on any other pain score. Side effects were negligible.
CONCLUSIONS: At doses of up to 900 mg/d, mexiletine has minimal effects on pain
and allodynia of neuropathic pain. However, side effects may preclude higher
doses.
PMID- 11009231
TI - Effect of oral mexiletine on capsaicin-induced allodynia and hyperalgesia: a
double-blind, placebo-controlled, crossover study.
AB - BACKGROUND AND OBJECTIVES: Mexiletine is a sodium channel blocker that has been
used for the treatment of a variety of neuropathic pain syndromes. A recent
double-blinded placebo-controlled study concluded that it was ineffective in the
treatment of allodynia associated with neuropathic pain. However, this study
failed to achieve adequate plasma levels of mexiletine. This was a study in
healthy volunteers that sought to push the drug to dose-limiting side effects and
then evaluate the effects on human experimental pain. METHODS: Twelve healthy
volunteers were studied using a randomized, double-blind, placebo-controlled
crossover study. The subjects were titrated to a maximum dose of 1,350 mg/d or
dose-limiting side effects, whichever occurred first. At baseline and day 10 and
17, neurosensory testing, train-of-three thermal pulses, and side-effect
measurements were performed and on day 17, intradermal capsaicin was injected on
the volar aspect of the forearm and the pain and secondary hyperalgesia to von
Frey hair, stroking, and thermal stimuli were measured. RESULTS: Peak plasma
levels occurred on day 10 and were 0.36 +/- 0.21 microg/mL. All subjects
experienced dose-limiting side effects. The mean maximum tolerable daily dose
achieved was 859 mg (range, 300 to 1,350 mg). The side effects reported by the
subjects included nausea, lightheadedness, muscle twitching and weakness, blurred
vision, headache, tremors, difficulty concentrating, dysphoria, sedation,
pruritus, and rash. These side effects occurred at an average daily dose of 993
mg (range, 600 to 1,350 mg). Compared with placebo, mexiletine had no significant
effects on any of the neurosensory thresholds and pain scores after intradermal
capsaicin. There was a significant reduction in the area of secondary
hyperalgesia to von Frey hair stimulation only. There was a significant
correlation between plasma mexiletine level and flare response. CONCLUSIONS:
Mexiletine has minimal effects on human experimental pain. It is severely limited
by side effects and tolerable doses seem to be void of effects on normal
neurosensation and facilitated pain induced by capsaicin and thermal heat pulses.
PMID- 11009232
TI - Current perception thresholds and postoperative pain in schizophrenic patients.
AB - BACKGROUND AND OBJECTIVES: Schizophrenic patients may have less sensitivity to
pain; however, pain insensitivity in schizophrenia has not been adequately
evaluated. We investigated current perception threshold (CPT) and postoperative
pain intensity in patients with long-standing and treated schizophrenia and
control patients. METHODS: We measured CPTs for 2,000 Hz, 250 Hz, and 5 Hz and
postoperative pain intensity using a visual analogue scale (VAS) in 50 chronic
schizophrenic patients who were on chronic phenothiazine derivatives (> 10 years)
and for 25 control patients. RESULTS: CPTs for 2,000 Hz, 250 Hz, and 5 Hz in
schizophrenic patients were 334.2 +/- 112.2, 303.9 +/- 117.1, and 165.0 +/- 72.3,
respectively. CPTs for 2,000 Hz, 250 Hz, and 5 Hz in schizophrenic patients were
significantly higher than those of control patients. VAS pain scores of
schizophrenic patients were 4.0 +/- 1.7 at 2 hours post-operatively and 3.8 +/-
1.5 at 5 hours postoperatively, which were significantly (P < .05) lower than
those (5.0 +/- 1.6 and 5.1 +/- 1.9) of the control group. CONCLUSIONS: Chronic
schizophrenic patients have increased current perception threshold and lower VAS
pain scores in postoperative pain compared with control patients.
PMID- 11009233
TI - Comparison of 0.5% intrathecal bupivacaine with 0.5% intrathecal ropivacaine in
the treatment of refractory cancer and noncancer pain conditions: results from a
prospective, crossover, double-blind, randomized study.
AB - BACKGROUND AND OBJECTIVES: Intrathecal (IT) administration of bupivacaine (BUP)
for treatment of "refractory" pain has sometimes been associated with
unacceptable side effects. This study was undertaken to determine if IT
ropivacaine (ROP) can reduce the rate and intensity of these side effects e.g.,
urinary retention, paresthesia, and particularly, paresis with gait impairment. A
prospective, crossover, double-blind, randomized study. METHODS: Twenty-one
patients were enrolled, 9 dropped out of the study, and data were analyzed from
12 patients. Patients were treated by insertion of IT tunneled nylon catheters,
continuous infusion of 0.5% ROP followed by 0.5% BUP or 0.5% BUP followed by 0.5%
ROP solutions from an external electronic pump. Each local anesthetic was infused
for 7 days, and their order of infusion randomized. The comparative efficacy of
the ROP and BUP IT infusions was assessed from the daily doses of IT ROP and IT
BUP, oral and parenteral opioids, and daily scores of nonopioid analgetic and
sedative drug consumption. Self-reported pain intensity (visual analogue scale
[VAS] mean scores) and scores of Bromage relaxation, ambulation, nocturnal sleep
pattern, rates of side-effects attributable to the IT drugs, the patients'
assessment of the IT ROP v the IT BUP periods of the trial, and the comparative
daily cost of IT ROP v IT BUP were recorded. RESULTS: The daily doses of the
local anesthetics used were 23% higher for ROP than for BUP. Further, the daily
cost was approximately equals 3 times higher for ROP than for BUP. No other
significant differences between IT ROP and IT BUP were found. CONCLUSION: The
results of this study do not support the hypothesis that IT infusion of 0.5% ROP
has advantages over IT infusion of 0.5% BUP when administered for relief of
"refractory" pain.
PMID- 11009234
TI - Technical aspects and postoperative sequelae of spinal and epidural anesthesia: a
prospective study of 3,230 orthopedic patients.
AB - BACKGROUND AND OBJECTIVES: Major complications after spinal or epidural
anesthesia are extremely rare. The occurrence of less serious and transient
sequelae and complaints may be underestimated if there is no established
organization for the systematic and continuous surveillance of patients after
anesthesia. This study was designed to evaluate the possible relationship between
various block-related occurrences and the intra- and postoperative side effects
and complaints. METHODS: This prospective study included 3,230 orthopedic
patients operated on under neuraxial block. The block was performed by single
dose (single-shot spinal anesthesia [SPIN], 80.6%), continuous spinal anesthesia
(CSA, 10.3%), or combined spinal and epidural anesthesia (CSE, 9.1%) technique.
The patient position during surgery and a detailed description of block
performance and equipment, as well as all intraoperative problems, were
immediately recorded. Every patient was given a standardized questionnaire to be
completed and returned after 1 week. RESULTS: The overall incidence of
paresthesia was 12.8%, being most frequent during spinal catheter insertion with
multiple attempts. Postoperative sensory disturbances (numbness, dysesthesia)
occurred unrelated to paresthesia elicited by the puncture or catheterization.
The failure rates (SPIN, 1.0%; CSA, 1.5%; and CSE, 1.0%) were quite low. Asystole
with successful resuscitation, occurred in 1 patient with CSE but, overall,
hemodynamic perturbations were more common with the continuous techniques. On the
first postoperative day, decreased sensation of the skin was significantly more
frequent after the continuous techniques, still present in 6.5% of SPIN patients,
6.1% of CSA patients, and 17.2% of CSE patients 1 week after surgery. These
disturbances were also related to the use of a tourniquet and lateral position of
the patient during surgery. The frequency of postdural puncture headache (PDPH)
was similar for the different techniques (SPIN, 0.9%; CSA, 1.5%; and CSE, 1.7%).
About one third of the patients reported strong postoperative pain on the day
after the operation, and 5.6% continued to report this at 1 week. CONCLUSIONS:
Although sensory changes were quite frequent, they were mild and transient.
Rather than having been caused by the anesthetic technique, per se, a
"nonanesthetic" reason (position, tourniquet, immobilization) should also be
considered as their origin. Sensory disturbances, as well as strong pain for at
least a week, were reported by several patients, and to become aware of these
problems and improve the quality of treatment, a universal regional anesthesia
follow-up system is recommended.
PMID- 11009235
TI - Is urinary drainage necessary during continuous epidural analgesia after colonic
resection?
AB - BACKGROUND AND OBJECTIVES: Postoperative urinary retention may occur in between
10% and 60% of patients after major surgery. Continuous lumbar epidural
analgesia, in contrast to thoracic epidural analgesia, may inhibit urinary
bladder function. Postoperative urinary drainage has been common in patients with
continuous epidural analgesia, despite the lack of scientific evidence for its
indication after thoracic epidural analgesia. This study describes 100 patients
who underwent elective colonic resection with 48 hours of continuous thoracic
epidural analgesia and only 24 hours of urinary drainage. METHODS: This is a
prospective, uncontrolled study with well-defined general anesthesia,
postoperative analgesia, and nursing care programs in patients with a planned 2
day hospital stay, urinary catheter removal on the first postoperative morning,
and epidural catheter removal on the second postoperative morning. Follow-up in
the outpatient clinic was on days 8 and 30. RESULTS: Nine patients needed bladder
recatheterization, 8 as a single procedure and 1 patient a second
recatheterization with removal on day 7. This patient had urinary infection on
day 10 and was readmitted for 5 days because of urosepsis and, subsequently, for
cystitis and left-sided epididymitis. Three patients had uncomplicated urinary
infection. No patients had urological complaints at 30 days follow-up (95%
confidence limit, 0% to 3.6%). CONCLUSION: The low incidence of urinary retention
(9%) and urinary infection (4%) suggests that routine bladder catheterization
beyond postoperative day 1 may not be necessary in patients with ongoing
continuous low-dose thoracic epidural analgesia.
PMID- 11009236
TI - Effect of clonidine on upper extremity tourniquet pain in healthy volunteers.
AB - BACKGROUND AND OBJECTIVES: Tourniquet pain is often a limiting factor during
intravenous regional anesthesia (IVRA). The purpose of this study was to evaluate
the efficacy of 1 microg/kg of clonidine added to IVRA-lidocaine in decreasing
the onset of severe tourniquet pain. METHODS: Upper extremity IVRA was performed
in 15 volunteers with a double-cuffed tourniquet on 2 separate occasions at least
1 week apart. IVRA was established with either 40 mL 0.5% lidocaine (IVRA-L) or
40 mL 0.5% lidocaine with 1 microg/kg clonidine (IVRA-Cl). Verbal pain scores
(VPS) from 0 to 10 were recorded every 5 minutes. When the VPS reached 6, the
distal cuff was inflated, and the proximal cuff was deflated. This was defined as
the first tourniquet time (T1). The study was terminated at a VPS of 10, or at 60
minutes, whichever occurred first. The time from distal cuff inflation to
deflation was defined as the second tourniquet time (T2). Total tourniquet time
(TT) was the sum of T1 and T2. RESULTS: T1 for IVRA-L (21.6 +/- 3.9) and IVRA-Cl
(22.7 +/- 2.7) were not significantly different. T2 and TT were significantly
longer (P < .0001; P < .0007, respectively) for IVRA-Cl (33.0 +/- 6.2; 55.6 +/-
6.6) than for IVRA-L (25.5 +/- 4.4; 47.1 +/- 5.2). CONCLUSION: This study shows
that the addition of 1 microg/kg of clonidine to 40 mL of 0.5% IVRA-L delays the
onset time of tourniquet pain in healthy, unsedated volunteers.
PMID- 11009237
TI - Postoperative analgesia after peripheral nerve block for podiatric surgery:
clinical efficacy and chemical stability of lidocaine alone versus lidocaine plus
ketorolac.
AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether the
addition of ketorolac tromethamine to local anesthesia for ankle block alters the
quality or duration of analgesia after podiatric surgery. The second aim was to
determine the chemical stability of ketorolac tromethamine when added to local
anesthetic solutions. METHODS: The study design was double-blinded, placebo
controlled, and randomized. Seventy-nine American Society of Anesthesiologists
(ASA) class I or II patients scheduled for bunionectomy or hammer toe repair, or
both were randomized to 1 of 4 groups. Group L received plain 1.73% lidocaine for
their ankle block. Group K received 1.73% lidocaine with ketorolac (4 mg/mL)
added to the local solution. Group Kiv received 1.73% plain lidocaine for ankle
block and 20 mg of ketorolac intravenously. Group E received 1.73% lidocaine with
.67% ethanol added. The final concentration of lidocaine for all groups was
1.73%. The block performed in each patient was a 5-point ankle block. Beginning
at 1 hour after the completion of the block and every 30 minutes thereafter,
visual analogue scale (VAS) and verbal pain scores were recorded. The time from
performance of the block to the initial pain and time to the first oral pain
medication intake were also recorded. The time and amount of postoperative oral
analgesics in the first 9 hours after the block were recorded. Adverse events
were also recorded for each group. RESULTS: There were significantly lower
overall VAS and verbal pain scores for group K compared with groups E and L and
group Kiv compared with group E. Group K also had a significantly longer time to
the first reported pain and first oral pain medications than groups E and L, but
not with Group Kiv. The same group had significantly fewer average doses of pain
medications postoperatively than Groups E and L. Group E had significantly
shorter times to first report of pain and first pain medications and higher mean
dose of postoperative oral analgesics than group K and Group Kiv. There were no
untoward side effects reported from any group. Chemical analysis by gas
chromatography (GC) and capillary electrophoresis (CE) showed no significant
change in composition of the solutions when ketorolac was mixed with lidocaine
and/or bupivacaine and stored at 37 degrees C for 1 week. CONCLUSIONS: The
addition of ketorolac to lidocaine for ankle block contributed to longer duration
and better quality analgesia after foot surgery compared with plain 1.73%
lidocaine or 1.73% lidocaine plus intravenous ketorolac. The ethanol vehicle is
unlikely responsible for the analgesic effects of ketorolac. Ketorolac retains
its chemical stability when placed in local solutions of lidocaine or
bupivacaine.
PMID- 11009238
TI - Alkalinized lidocaine and bupivacaine with hyaluronidase for sub-tenon's
ophthalmic block.
AB - BACKGROUND AND OBJECTIVES: Alkalinization of local anesthetics has been shown to
decrease the onset and prolong the duration of block for extraconal and
intraconal application in ocular surgery. The objective of this study is to
determine if alkalinization is also effective in sub-Tenon's block when
hyaluronidase is added to the drug mixture. METHODS: Twenty-nine patients were
randomly assigned to 2 groups in a double-blind, prospective fashion to receive
5.125 mL of either a plain mixture LBH (2.5 mL lidocaine 2%, 2.5 mL bupivacaine
0.5%, 5 IU/mL hyaluronidase, and 0.125 mL isotonic saline) or pH-adjusted mixture
LBH-PH (2.5 mL lidocaine 2%, 2.5 mL bupivacaine 0.5%, 5 IU/mL hyaluronidase, and
0.125 mL sodium bicarbonate 8.4%) of local anesthetics in a 1-quadrant sub
Tenon's block. Time to onset and time to full akinesia were determined every 30
seconds. RESULTS: No difference was found between the study groups. CONCLUSION:
pH adjustment of the local anesthetic mixture of lidocaine, bupivacaine, and
hyaluronidase offered no additional benefit in sub-Tenon's technique in ocular
procedures.
PMID- 11009239
TI - Alkalinization and precipitation characteristics of 0.2% ropivacaine.
AB - BACKGROUND AND OBJECTIVES: Alkalinization of local anesthetics has been used to
increase the speed of onset of nerve blocks. However, alkalinization of local
anesthetic solutions may cause precipitation, thereby decreasing bioavailability
and anesthetic activity. Alkalinization of ropivacaine has not been described.
This laboratory study assessed the alkalinization and precipitation
characteristics of ropivacaine. METHODS: Aliquots (2 mL) of commercially
available ropivacaine (Naropin, 0.2%; Astra Pharmaceutical, Westborough, MA) were
alkalinized with increasing amounts (0.01, 0.02, 0.04 mL) of sodium bicarbonate
(8.4%) and immediately monitored for pH change and onset of visible precipitation
at room temperature. We then alkalinized ropivacaine with sodium bicarbonate and
measured the amount of precipitate that accumulated after various incubation
times. RESULTS: The pH of ropivacaine increases with the addition of small
amounts of bicarbonate. The calculated percentage of nonionized ropivacaine
increased from 0.3% to greater than 30% with alkalinization from pH of 5.51 to
7.63. Drug loss to precipitation increased with higher doses of bicarbonate,
reaching 25% to 30% of the total ropivacaine. Even with a low dose of bicarbonate
(0.1 mL bicarbonate/20 mL ropivacaine), precipitation increased with time of
incubation, reaching a plateau at 20 minutes. CONCLUSIONS: A laboratory
evaluation that establishes the alkalinization characteristics of ropivacaine is
a prerequisite for designing a clinical study of alkalinized ropivacaine. In our
experiment, low doses of bicarbonate produced significant increases in the
proportion of nonionized ropivacaine with only modest precipitation. There would
be a low likelihood of substantial drug precipitation if the mixture was
administered within 5 to 10 minutes after alkalinization. These results indicate
that alkalinized ropivacaine should not be used for infusions and that
ropivacaine should not be alkalinized until just before use.
PMID- 11009240
TI - Antinociceptive and motor-blocking action of epidurally administered IQB-9302 and
bupivacaine in the dog.
AB - BACKGROUND AND OBJECTIVES: The aim of this study was to compare the
antinociceptive and motor-blocking effects of epidurally administered IQB-9302
(C18H26N2O.HCl) and bupivacaine in the dog. METHODS: Twelve adult female Beagle
dogs were used. Each animal received 3 concentrations (0.25%, 0.50%, and 0.75%)
of either IQB-9302 (n = 6) or bupivacaine (n = 6) by means of a chronic epidural
catheter. The nocifensive and motor-blocking status were determined at regular
intervals before (baseline) and after drug administration. RESULTS: Epidurally
administered IQB-9302 caused a more potent nocifensive and motor-blocking action
than bupivacaine. The duration of complete nocifensive block was the longest with
IQB-9302, whereas the duration of dermatome nocifensive block was similar for
both drugs. The nocifensive to motor block ratio was significantly higher with
IQB-9302. CONCLUSIONS: IQB-9302 produced an anesthetic action similar to that of
bupivacaine, although the former drug induced a slightly more potent nocifensive
block. Nocifensive and motor block duration are very similar with IQB-9302,
whereas bupivacaine induces a more prolonged motor block without nocifensive
block.
PMID- 11009241
TI - Effect of standard diluted epinephrine infusion on epidural anesthesia in labor.
AB - BACKGROUND AND OBJECTIVES: Epinephrine is used with local anesthetics to prolong
the duration of epidural analgesia and decrease the peak plasma concentrations of
local anesthetics. However, the duration of labor may be prolonged because
epinephrine reduces uterine activity. We designed a prospective, randomized, and
doubleblind study to examine the effects of epinephrine infusion on the quality
of analgesia and plasma concentration of local anesthetic, as well as the effect
on the uteroplacental circulation, duration of the first or second stage of
labor, and fetal outcome. METHODS: Twenty-four parturients received continuous
epidural bupivacaine 0.125% (8 mL/h) combined either with epinephrine (40
microg/h) (n = 12) or without epinephrine (n = 12) for analgesia during labor. If
patients requested additional analgesia, a bolus of 1% or 1.5% lidocaine (6 to 10
mL) was given. RESULTS: Only the plain bupivacaine group required additional
lidocaine. However, epinephrine infusion prolonged the median (range) duration of
the second stages of labor: 69 (21 to 231) minutes with epinephrine group versus
31 (8 to 99) minutes without epinephrine group (P < .05), and decreased pH in
umbilical artery at the time of delivery. Epinephrine infusion did not change the
uterine and umbilical blood flow, which were determined as the resistance
indices. Changes in the fetal heart rate and Apgar score were also comparable.
Epinephrine significantly reduced the umbilical venous to maternal arterial
bupivacaine concentration (P < .05). CONCLUSIONS: A standard diluted epinephrine
infusion (40 microg/h) into epidural space decreased anesthetic requirements. The
possibility of the prolonged duration of labor remains a problem.
PMID- 11009242
TI - Ondansetron for treatment of intrathecal morphine-induced pruritus after cesarean
delivery.
AB - BACKGROUND AND OBJECTIVES: Pruritus induced by intrathecal morphine is a concern
in many obstetric patients after cesarean delivery and may detract from the
benefit of postoperative pain relief. This study was performed to investigate the
efficacy of ondansetron (5-HT3 receptor antagonist) in treatment of pruritus
following intrathecal morphine. METHODS: Eighty parturients developing moderate
to severe pruritus following intrathecal morphine were randomly allocated into 2
groups. One group received 4 mg ondansetron while the other group received
placebo (normal saline). The improvement of pruritus and other adverse effects
such as pain scores, nausea, vomiting, sedation, hallucination, and respiratory
depression were determined at 30 minutes after study drugs' administration.
RESULTS: The treatment success rate was higher in the ondansetron group than in
the placebo group (80% v 36%, P < .001). Among the successfully treated patients,
the recurrence rates of moderate to severe pruritus within 4 hours after
administration of ondansetron and placebo were 12% and 70%, respectively (P <
.001). The number of patients with decreased nausea and vomiting score was also
higher in the ondansetron group (11 v 1, P < .006). CONCLUSION: Ondansetron
treats intrathecal morphine-induced pruritus after cesarean delivery,
particularly in patients suffering from both nausea/vomiting and pruritus.
PMID- 11009243
TI - Lumbar epidurography.
PMID- 11009244
TI - Neuropeptide-toxin conjugates in pain research and treatment.
PMID- 11009245
TI - Maternal fever, neonatal sepsis evaluation, and epidural labor analgesia.
AB - BACKGROUND AND OBJECTIVES: Numerous studies have found an association between
epidural analgesia for labor and maternal fever (temperature > or =38 degrees C).
Maternal fever often results in treatment with maternal or neonatal antibiotics,
neonatal sepsis evaluation, and increased costs. METHODS: Medline was used to
identify literature regarding the association between epidural labor analgesia
and maternal fever/neonatal sepsis. Studies examining thermoregulation during
pregnancy and/or epidural analgesia were also reviewed. RESULTS: There appears to
be a strong association between epidural labor analgesia and maternal fever. The
link between epidural labor analgesia and neonatal sepsis evaluation is less
clear. The incidence of confirmed neonatal sepsis does not increase with maternal
epidural analgesia. Causes of the association between epidural labor analgesia
and maternal fever include selection bias, altered thermoregulation, and
increased shivering or decreased sweating with epidural analgesia. CONCLUSIONS:
Maternal epidural labor analgesia is associated with maternal fever and possibly
increased neonatal sepsis evaluation. There is no proof the relationship is
causal.
PMID- 11009246
TI - Causal judgment from contingency information: the interpretation of factors
common to all instances.
AB - Participants made judgments about stimulus materials in which there were 2
possible causes of an outcome. One of these was a common factor, a factor present
in all instances presented for judgment, and the other was a positive covariate
of the outcome. Instead of interpreting the positive covariate as the cause,
participants consistently preferred an interpretation in which the common factor
was the cause and the positive covariate enabled the cause to produce its effect.
Participants' judgments of both interpretations were predicted by the proportion
of instances that were confirmatory for the interpretation and not by deltaP. The
findings support a hypothesis that people have a multirole conceptualization of
causality including, in addition to the roles of cause and effect, that of an
enabler, a factor the presence of which ensures that a thing is in a state of
readiness to produce a particular effect.
PMID- 11009247
TI - Age of acquisition effects in adult lexical processing reflect loss of plasticity
in maturing systems: insights from connectionist networks.
AB - Early learned words are recognized and produced faster than later learned words.
The authors showed that such age of acquisition effects are a natural property of
connectionist models trained by back-propagation when patterns are introduced at
different points into training and learning of early and late patterns is
cumulative and interleaved. Analysis of hidden unit activations indicated that
the age of acquisition effect reflects a gradual reduction in network plasticity
and a consequent failure to differentiate late items as effectively as early
ones. Further simulations examined the effects of vocabulary size, learning rate,
sparseness of coding, use of a modified learning algorithm, loss of early items,
acquisition of very late items, and lesioning the network. The relationship
between age of acquisition and word frequency was explored, including analyses of
how the relative influence of these factors is modulated by introducing weight
decay.
PMID- 11009248
TI - Task-set switching and long-term memory retrieval.
AB - The authors tested the hypothesis of a close relationship between the intentional
component of task-set switching ("advance reconfiguration;" R. D. Rogers & S.
Monsell, 1995) and long-term memory (LTM) retrieval. Consistent with this
hypothesis, switch costs are reported to be larger when the switched-to task
involves high retrieval demands (i.e., retrieval of episodic information) than
when it involves low retrieval demands (i.e., retrieval of semantic information).
In contrast, switch costs were not affected by a primary-task difficulty
manipulation unrelated to intentional retrieval demands (Experiment 2). Also, the
retrieval-demand effect on switch costs was eliminated when time for advanced
preparation or task cues explicitly specifying the task rules were provided
(Experiment 3). Overall, results were consistent with the hypothesis that the
intentional switch-cost component reflects the time demands of retrieving
appropriate task rules from LTM.
PMID- 11009249
TI - Similarity and inhibition in long-term memory: evidence for a two-factor theory.
AB - Recalling a past experience often requires the suppression of related memories
that compete with the retrieval target, causing memory impairment known as
retrieval-induced forgetting. Two experiments examined how retrieval-induced
forgetting varies with the similarity of the competitor and the target item
(target-competitor similarity) and with the similarity between the competitors
themselves (competitor-competitor similarity). According to the pattern
suppression model (M. C. Anderson & B. A. Spellman, 1995), high target-competitor
similarity should reduce impairment, whereas high competitor-competitor
similarity should increase it. Both predictions were supported: Encoding target
competitor similarities not only eliminated retrieval-induced forgetting but also
reversed it, whereas encoding competitor-competitor similarities increased
impairment. The differing effects of target-competitor and competitor-competitor
similarity may resolve conflicting results concerning the effects of similarity
on inhibition.
PMID- 11009250
TI - The properties of retention intervals and their affect on retaining prospective
memories.
AB - Five experiments were conducted to explore how the character of the retention
interval affected event-based prospective memory. According to the canons of
retrospective memory, prospective performance should have been worse with
increasing delays between intention formation and the time it was appropriate to
complete an action. That result did not occur. Rather, prospective memory was
better with increasing retention intervals in Experiments 1A, 1B, and 3. In
manipulating the nature of the retention interval, the authors found that there
were independent contributions of retention interval length and the number of
intervening activities, with more activities leading to better prospective memory
(Experiments 2 and 3). The identical retention intervals did not improve
retrospective memory in Experiment 4. Theoretical explanations for these
dissociations between prospective and retrospective memory are considered.
PMID- 11009251
TI - Adult age differences in memory performance: tests of an associative deficit
hypothesis.
AB - An associative hypothesis to explain and predict older adults' deficient explicit
episodic memory performance was outlined and tested. The hypothesis attributes a
substantial part of older adults' deficient memory performance to their
difficulty in merging unrelated attributes-units of an episode into a cohesive
unit. Although each of the components can be memorized to a reasonable degree,
the associations that tie the attributes-units to each other grow weaker in old
age. Four experiments are reported that provide (a) a converging validity to the
hypothesis by demonstrating this associative deficit for both interitem
relationships and intraitem relationships and (b) a discriminant validity to the
hypothesis by contrasting and testing competing predictions made by the
associative hypothesis and by alternative hypotheses. The implications of these
results to older adults' episodic memory performance are discussed.
PMID- 11009252
TI - Interresponse times in serial recall: effects of intraserial repetition.
AB - The authors examined the effects of intraserial repetition on multitrial serial
learning of random consonant lists, analyzing both learning rates and perfect
trial interresponse times (IRTs). Lists varied along 3 dimensions: list length,
presence or absence of a repeated element, and lag between repeated elements.
After achieving a forward-recall criterion on a given list, participants (N = 20)
attempted backward recall. At small lags, IRTs between the repeated elements were
very short (compared with IRTs from identical positions in nonrepetition lists).
At larger lags, the IRT to recall the second repeated item was substantially
longer than in control lists. These results reveal a latency analogue of the
Ranschburg pattern seen in accuracy data. A Ranschburg pattern was also found in
participants' learning rates. These results both generalize the Ranschburg
phenomenon and present further challenges to theories of serial order memory.
PMID- 11009253
TI - Repetition priming for familiar and unfamiliar faces in a sex-judgment task:
evidence for a common route for the processing of sex and identity.
AB - Repetition priming for faces was examined in a sex-judgment task given at test.
Priming was found for edited, hair-removed photos of unfamiliar and familiar
faces after a single presentation at study. Priming was also observed for the
edited photos when study and test faces were different exemplars. Priming was not
observed, however, when sex judgments were made at test to photos of complete,
hair-included faces. These findings were interpreted by assuming that, for edited
faces, internal features are attended, thereby activating face-recognition units
that support performance. With complete faces, however, participants provided
speeded judgments based primarily on the hairstyle. It is suggested that, for
both familiar and unfamiliar faces, a common locus exists for the processing of
the identity of a face and its sex. A single face-recognition model for the
processing of familiar and unfamiliar faces is advocated.
PMID- 11009254
TI - Gender stereotyping and decision processes: extending and reversing the gender
bias in fame judgments.
AB - M. R. Banaji and A. G. Greenwald (1995) demonstrated a gender bias in fame
judgments--that is, an increase in judged fame due to prior processing that was
larger for male than for female names. They suggested that participants shift
criteria between judging men and women, using the more liberal criterion for
judging men. This "criterion-shift" account appeared problematic for a number of
reasons. In this article, 3 experiments are reported that were designed to
evaluate the criterion-shift account of the gender bias in the false-fame effect
against a distribution-shift account. The results were consistent with the
criterion-shift account, and they helped to define more precisely the situations
in which people may be ready to shift their response criterion on an item-by-item
basis. In addition, the results were incompatible with an interpretation of the
criterion shift as an artifact of the experimental situation in the experiments
reported by M. R. Banaji and A. G. Greenwald.
PMID- 11009255
TI - Surface form typicality and asymmetric transfer in episodic memory for spoken
words.
AB - A series of experiments was conducted to determine whether the typicality of the
surface form of speech would affect memory retention of spoken words. For each
surface characteristic studied, a continuous-recognition-memory task was used in
which listeners based recognition judgments on word identity alone. For "typical"
items, repetition benefits did not depend on whether the surface forms of the 1st
and 2nd occurrences matched or mismatched. For "atypical" items, a larger
repetition benefit occurred when the surface forms of the 2 occurrences matched.
These results suggest that episodic memory for spoken words may be directly
related to the perceived typicality of particular surface characteristics.
PMID- 11009256
TI - The relative time course of semantic and phonological activation in reading
Chinese.
AB - The relative time course of semantic and phonological activation was investigated
in the context of whether phonology mediates access to lexical representations in
reading Chinese. Compound words (Experiment 1) and single-character words
(Experiments 2 and 3) were preceded by semantic and phonological primes. Strong
semantic priming effects were found at both short (57 ms) and long (200 ms)
stimulus onset asynchrony (SOA), but phonological effects were either absent in
lexical decision (Experiment 1), were present only at the longer SOA in character
decision (Experiment 2) or were equally strong as semantic effects in naming
(Experiment 3). Experiment 4 revealed facilitatory or inhibitory effects,
depending on SOA, in phonological judgments to character pairs that were not
phonologically but semantically related. It was concluded that, in reading
Chinese, semantic information in the lexicon is activated at least as early and
just as strongly as phonological information.
PMID- 11009257
TI - Effects of sentence constraint on priming in natural language comprehension.
AB - In 4 cross-modal naming experiments, researchers investigated the role of
sentence constraint in natural language comprehension. On the sentence constraint
account, incoming linguistic material activates semantic features that in turn
pre-activate likely upcoming words. The 1st and 2nd experiments investigated
whether stimulus offset asynchrony played a critical role in previous studies
supporting the sentence constraint account. The 3rd and 4th experiments examined
further predictions of the sentence constraint account, in particular whether pre
activated words would compete for activation. In Experiment 3, the researchers
manipulated whether an expected target word had a close competitor and found that
response to the expected word was facilitated regardless of the proximity of a
competitor. The 4th experiment established that close competitors were primed by
the sentence frames and should have been available to compete with expected
target words. Thus, word-level representations did not compete for activation.
PMID- 11009258
TI - The cognate facilitation effect: implications for models of lexical access.
AB - Do nonselected lexical nodes activate their phonological information? Catalan
Spanish bilinguals were asked to name (a) pictures whose names are cognates in
the 2 languages (words that are phonologically similar in the 2 languages) and
(b) pictures whose names are noncognates in the 2 languages. If nonselected
lexical nodes are phonologically encoded, naming latencies should be shorter for
cognate words, and because the cognate status of words is only meaningful for
bilingual speakers, this difference should disappear when testing monolingual
speakers. The results of Experiment 1 fully supported these predictions. In
Experiment 2, the difference between cognate and noncognate words was larger when
naming in the nondominant language than when naming in the dominant language. The
results of the 2 experiments are interpreted as providing support to cascaded
activation models of lexical access.
PMID- 11009259
TI - The role of mediators in memory retrieval as a function of practice: controlled
mediation to direct access.
AB - The role of prior knowledge in retrieval of Spanish-English vocabulary pairs
learned using keyword mediators was examined in 4 experiments. Retrieval was
tested immediately after learning and after 1-week and 1-month no-practice
intervals (Experiment 1), after moderate retrieval practice (Experiment 2), and
after extended retrieval practice (Experiments 3 and 4). Using accuracy, latency,
and verbal report data, a detailed account of memory retrieval processes was
developed. Initial retrieval is an explicit mediation process that involves
retrieving keyword mediators into working memory and using them as retrieval cues
to access the English equivalents of the Spanish words. After extended vocabulary
retrieval practice, this sequential mediation process qualitatively changed to a
direct retrieval process in which the English equivalent was accessed in a single
working memory step. However, direct retrieval was still influenced by a covert
mediation process.
PMID- 11009260
TI - Counterfactual thinking about actions and failures to act.
AB - When people think counterfactually about how a situation could have turned out
differently, they mentally undo events in regular ways (e.g., they focus on
actions not failures to act). Four experiments examine the recent discovery that
the focus on actions in the short term switches to inactions in the long term.
The experiments show that this temporal switch occurs only for particular sorts
of situations. Experiment 1 showed no temporal pattern to the agency effect when
112 participants judged emotional impact and frequency of "if-only" thoughts from
both short- and long-term perspectives for an investment scenario. Experiment 2
showed no temporal pattern when 190 participants considered a college choice
scenario with a good outcome. Experiment 3 showed no temporal pattern when 131
participants considered an investment scenario even when the situation for the
actor and nonactor was bad from the outset. Experiment 4, with 113 participants,
showed a focus on actions even when the investment loss was equal for both the
actor and nonactor. The implications of the results are discussed in terms of
what is explicitly available in the mental representation of actions and
inactions.
PMID- 11009261
TI - Assessing the empirical validity of the "take-the-best" heuristic as a model of
human probabilistic inference.
AB - The boundedly rational 'Take-The-Best" heuristic (TTB) was proposed by G.
Gigerenzer, U. Hoffrage, and H. Kleinbolting (1991) as a model of fast and frugal
probabilistic inferences. Although the simple lexicographic rule proved to be
successful in computer simulations, direct empirical demonstrations of its
adequacy as a psychological model are lacking because of several methodical
problems. In 4 experiments with a total of 210 participants, this question was
addressed. Whereas Experiment 1 showed that TTB is not valid as a universal
hypothesis about probabilistic inferences, up to 28% of participants in
Experiment 2 and 53% of participants in Experiment 3 were classified as TTB
users. Experiment 4 revealed that investment costs for information seem to be a
relevant factor leading participants to switch to a noncompensatory TTB strategy.
The observed individual differences in strategy use imply the recommendation of
an idiographic approach to decision-making research.
PMID- 11009262
TI - Impact of end-stage renal disease on clinical and angiographic outcomes after
coronary stenting.
AB - Although patients with end-stage renal disease (ESRD) are at high risk for
restenosis that requires repeat revascularization after balloon angioplasty,
their restenosis rate after coronary stenting is still unknown. Over a 4-year
period, we performed coronary stenting on 40 lesions in 34 patients with ESRD. We
compared these lesions with 80 lesions from patients without renal disease who
underwent coronary stenting in the STARS and WINS clinical trials, matched for
treatment site, diabetes, lesion length, and reference vessel diameter.
Quantitative coronary angiography was performed on all lesions and clinical
outcomes were assessed at 9-month follow-up. Clinical and angiographic
characteristics were well matched between the 2 groups and acute clinical success
rates were similar. Despite comparable initial angiographic results over the 9
month follow-up period, repeat target lesion revascularization was twice as
frequent in the ESRD group compared with the control group (35% vs 16%, p <0.05).
After adjusting for differences in postprocedural minimum lumen diameter and
other angiographic and clinical characteristics, ESRD remained the most important
predictor of late target lesion revascularization (relative risk = 2.3, p =
0.04). In addition, overall 9-month mortality was higher for ESRD patients than
for the control population (18% vs 2%, p <0.01). Thus, despite similar
angiographic results, patients with ESRD are at higher risk for target lesion
revascularization after coronary stenting than controls. Nonetheless, most
patients with ESRD do not develop restenosis after stent placement, suggesting an
important role for stenting in the management of this challenging population.
PMID- 11009263
TI - Effect of coronary artery bypass surgery on myocardial perfusion and ejection
fraction response to inotropic stimulation in patients without improvement in
resting ejection fraction.
AB - The aim of this study was to assess the effect of coronary artery bypass grafting
(CABG) on myocardial perfusion and left ventricular (LV) contractile reserve in
patients with reduced ejection fraction (EF). We studied 57 patients (age 59 +/-
8 years, 46 men and 11 women) with EF < or = 40% referred for CABG with
dobutamine (up to 40 microg/kg/min) stress-reinjection thallium-201 single-photon
emission computed tomography, and radionuclide ventriculography at rest and at
low-dose dobutamine before and 3 months after CABG. An increase in resting EF >
or = 5% occurred in 12 patients (group A) after CABG (EF 34% before and 46% after
CABG), whereas no increase occurred in the remaining 45 patients (group B) (EF
34% before and 32% after CABG). A significant increase in EF from rest to low
dose dobutamine radionuclide ventriculography occurred before and after CABG. The
magnitude of increase was more significant after than before CABG in group A (12%
vs 7%) as well as in group B (13% vs 7%, both p <0.001). Patients in both groups
had a significant reduction in stress, rest, and ischemic perfusion scores after
CABG. However, the percentage of reduction in resting perfusion defect score was
more significant in group A than in group B (60% vs 30%, respectively, p <0.01).
It is concluded that CABG induces a significant improvement in resting myocardial
perfusion and EF response to inotropic stimulation, even in the absence of
improved EF at rest. Patients without improvement in resting EF after CABG have
mild improvement in resting myocardial perfusion that may be sufficient to
increase EF after CABG during inotropic stimulation, but not at rest. We describe
the myocardium with these characteristics as "the reactive myocardium."
PMID- 11009264
TI - Coronary artery calcium evaluation by electron beam computed tomography and its
relation to new cardiovascular events.
AB - Electron beam computed tomography is widely used to screen for coronary artery
calcium (CAC). We evaluated the relation of CAC to future cardiovascular disease
events in 926 asymptomatic persons (735 men and 191 women, mean age 54 years) who
underwent a baseline electron beam computed tomographic scan. All subjects
included in this report returned a follow-up questionnaire 2 to 4 years (mean
3.3) after scanning, inquiring about myocardial infarction, stroke, and
revascularizations. Sixty percent of men and 40% of women had a positive scan at
baseline. Twenty-eight cardiovascular events occurred and were confirmed by
blinded medical record review. The presence of CAC (a total calcium score of >0)
and increasing score quartiles were related to the occurrence of new myocardial
infarction (p <0.05), revascularizations (p <0.001), and total cardiovascular
events (p <0.001). Those with scores at or above the median (score of 5) had a
relative risk of 4.5 (p <0.01) for new events. From Cox regression models,
adjusted for age, gender, and coronary risk factors, the relative risks for those
with scores of 81 to 270 and -271 (compared with 0) for cardiovascular events
were 4.5 (p <0.05) and 8.8 (p <0.001), respectively. These data support previous
reports showing CAC to be a modest predictor of future cardiovascular events.
PMID- 11009265
TI - Effects of cilostazol on angiographic restenosis after coronary stent placement.
AB - This study evaluates the impact of cilostazol on post-stenting restenosis.
Cilostazol is a potent antiplatelet agent with antiproliferative properties. Few
data are available about the effect of cilostazol on poststenting restenosis.
Four hundred nine patients (494 lesions) who were scheduled for elective stenting
were randomized to receive aspirin plus ticlopidine (group I, n = 201, 240
lesions) or aspirin plus cilostazol (group II, n = 208, 254 lesions), starting 2
days before stenting. Ticlopidine was given for 1 month and cilostazol for 6
months. Follow-up angiography was performed at 6 months, and clinical evaluation
at regular intervals. Baseline characteristics were similar between the 2 groups.
The procedural success rate was 99.6% in group I and 100% in group II. There were
no cases of stent thrombosis after stenting. Angiographic follow-up was performed
in 380 of the 494 eligible lesions and the angiographic restenosis rate was 27%
in group I and 22.9% in group II (p = NS). However, diffuse type in-stent
restenosis was more common in group I than in group II (54.2% vs 26.8%,
respectively, p <0.05). In diabetic patients, the angiographic restenosis rate
was 50% in group I and 21.7% in group II (p <0.05). Clinical events during follow
up did not differ between the 2 groups. In conclusion, aspirin plus cilostazol
seems to be an effective antithrombotic regimen with comparable results to
aspirin plus ticlopidine, but it does not reduce the overall angiographic
restenosis rate after elective coronary stenting.
PMID- 11009266
TI - Cerebral hemodynamics in carotid sinus syndrome and atrioventricular block.
AB - Carotid sinus syndrome (CSS) is a cause of syncope due to exaggerated
baroreceptor-mediated cardioinhibitory/vasodepressive reflexes. We sought to
determine if cerebral hemodynamics and regulation were specifically altered in
these patients by comparison with pure asystole without vasodepression in
patients with atrioventricular block (AVB). Mean blood flow velocity
(transcranial Doppler sonography) and mean arterial blood pressure (Finapres)
were recorded during cardioinhibition induced by carotid massage in patients with
CSS (n = 14, 75 +/- SD 8 years) and asystole induced by temporary pacemaker
inhibition in patients with complete AVB (n = 10, 69 +/- 11 years).
Cerebrovascular resistance was estimated by the arterial pressure/cerebral flow
velocity ratio, and dynamic cerebral autoregulatory responses were determined by
the rate of regulation and autoregulatory index. Asystole and cardioinhibition
each induced a decrease in arterial pressure (CSS 55 +/- 9% vs AVB 40 +/- 14%, p
<0.05) and cerebral flow velocity (CSS 66 +/- 19% vs AVB 69 +/- 14%, p = NS),
with an initial transient increase in cerebrovascular resistance (CSS 102 +/-
136% vs AVB 128 +/- 92%, p = NS) followed by a decrease (CSS 38 +/- 12%, AVB 29
+/- 13%, p = NS). The rate of regulation and autoregulatory index were higher
with AVB (0.43 +/- 0.20 and 8.5 +/- 1.1 second(-1)) than CSS (0.20 +/- 0.12 and
4.8 +/- 1.3 second(-1), respectively, p <0.01 and p <0.001 vs AVB). During
asystole and vasodepression, cerebral hypoperfusion in CSS is normally
compensated for by cerebral autoregulation. The lower rate of regulation in CSS
compared with AVB likely results from persistent peripheral vasodepression
triggered by carotid massage.
PMID- 11009267
TI - Subclinical left ventricular dysfunction in systemic hypertension and the role of
24-hour blood pressure.
AB - The relation between blood pressure (BP) and left ventricular (LV) systolic
function in systemic hypertension is controversial. We assessed the relation of
LV midwall fractional shortening (FS) to 24-hour BP in 1,702 never-treated
hypertensive subjects (age 48 +/- 12 years), who underwent 24-hour BP monitoring
and echocardiography. Stress-corrected endocardial and midwall FS (the latter
calculated taking into account the epicardial migration of midwall during
systole) were predicted in hypertensives on the basis of the values observed in
130 healthy normotensives (age 43 +/- 13 years, office BP 126/78 mm Hg). Subjects
below the fifth percentile of observed-to-predicted FS had depressed LV function.
The use of midwall FS resulted in an increase from 3.5% to 17.5% in the
proportion of patients with depressed chamber function. Compared with the group
with normal function, subjects with low midwall LV function had similar office
systolic BP (155 +/- 21 vs 154 +/- 17 mm Hg), but increased 24-hour systolic BP
(140 +/- 17 vs 133 +/- 12 mm Hg, p <0.001). Midwall FS had a closer negative
relation to 24-hour systolic BP than to office systolic BP (r = -0.27 vs -0.08, p
<0.001), whereas this difference was not apparent for diastolic BP (r = -0.23 vs
0.20). Compared with endocardial FS, midwall FS had a stronger inverse
association to LV mass (r = -0.45 vs -0.16, p <0.001). Thus, an increased 24-hour
BP load may chronically lead to depressed myocardial function in systemic
hypertension in the absence of clinically overt heart disease.
PMID- 11009268
TI - Effects of pravastatin on left ventricular mass in patients with hyperlipidemia
and essential hypertension.
AB - Left ventricular (LV) mass is a powerful predictor for future cardiovascular
events. Epidemiologic studies have shown that hyperlipidemia is associated with
higher LV mass. The effects of statin therapy for hyperlipidemia on LV mass have
not been studied. To determine the effects of statin therapy on LV mass, we
prospectively studied 3 groups of age and body surface area-matched patients:
group 1 (n = 20), patients with systemic hypertension and hyperlipidemia treated
with pravastatin plus anti-hypertensive drugs; group 2 (n = 20), patients with
hypertension and hyperlipidemia treated with hypertensive agents and diet control
alone; and group 3 (n = 20), hypertensive patients with normolipidemia treated
with antihypertensive agents. A group of controls without hypertension or
hyperlipidemia was used for comparison. Echocardiograms were recorded at baseline
and after 6-month therapy. All hypertensive groups showed significant decreases
in LV mass index after treatment. Group 1 had the greatest decrease in LV mass
and it was significantly higher than in groups 2 and 3. Multivariate analysis
revealed that regression of LV mass was significantly correlated only with the
use of statins and sex (p = 0.005 and 0.01, respectively, R(2) = 0.47). Linear
regression analysis in group 1 showed a significant correlation between changes
in arterial compliance and LV mass regression (r = 0.57, p = 0.01). Thus, the
addition of a statin may have an additional effect on reducing LV mass,
independent of lipid-lowering effects.
PMID- 11009269
TI - Containment of heart failure hospitalizations and cost by angiotensin-converting
enzyme inhibitor dosage optimization.
AB - Using our model relating angiotensin-converting enzyme (ACE) inhibitor dosing and
outcomes in heart failure (HF), we designed a prospective intervention trial for
patients with systolic dysfunction. A clinical pharmacist initiated or titrated
ACE inhibitor therapy or adjusted other medications within an HF management
program based on Agency for Healthcare Policy and Research guidelines. Entry into
the protocol required the approval of the attending physician. All patients
received dietary, nursing, rehabilitation, social service, and clinical pharmacy
consultations. Treatment conformed to Agency for Healthcare Policy and Research
guidelines in 25% of patients (group A). Suboptimal therapy (75% of patients) was
usually due to failure to administer an ACE inhibitor (48%) or inadequate dosing
of an ACE inhibitor (46%). In 62% of suboptimal cases, the attending physician
agreed to follow the clinical pharmacist's recommendations (group B). Patients of
physicians who declined pharmacist intervention served as a negative control
(group C). On admission, mean enalapril-equivalent daily doses in groups A, B,
and C were 30, 4, and 6 mg, respectively, and at discharge, 36, 18, and 6 mg,
respectively. At 180 days, rehospitalization frequency and total charges were
lower in groups A (31% and $5,600) and B (35% and $3,800) than in group C (63% [p
<0.004] and $9,800 [p <0.04]). Thus, optimization of ACE inhibitor doses by a
clinical pharmacist can greatly improve rehospitalization rates and significantly
lower cost of care in an HF management program.
PMID- 11009270
TI - Transcardiac extraction of circulating endothelin-1 across the failing heart.
AB - To determine the transcardiac gradient of plasma endothelin-1 (ET-1) in patients
with congestive heart failure (CHF), we measured plasma levels of ET-1 in both
the aortic root and the coronary sinus in 14 normal subjects and 79 consecutive
patients with CHF. In normal subjects, plasma ET-1 was significantly higher in
the coronary sinus than in the aortic root; these findings were also shown in
patients with mild CHF, suggesting that there was ET-1 spillover across the
heart. In contrast, plasma ET-1 was significantly lower in the coronary sinus
than in the aortic root in patients with severe CHF, suggesting there was ET-1
extraction across the heart in patients with severe CHF. The transcardiac
gradient of plasma ET-1 was correlated with the left ventricular end-diastolic
volume index (r = 0.501, p <0.0001) and plasma level of procollagen type III
amino terminal peptide in the coronary sinus (r = 0.54, p = 0.0008), a marker of
myocardial fibrosis. Stepwise multivariate analysis showed that the transcardiac
gradient of plasma ET-1 was an independent and significant relation with the left
ventricular end-diastolic volume index in patients with CHF (r = 0.665, p
<0.0001). These findings suggest that elevated circulating ET-1 is extracted
across the failing heart with a significant correlation between the transcardiac
gradient of plasma ET-1 and the left ventricular end-diastolic volume index,
suggesting that ET receptors are upregulated in the failing ventricle and that
the elevated circulating ET-1 might stimulate the process of left ventricular
remodeling in patients with severe CHF.
PMID- 11009271
TI - Predictors of left atrial spontaneous echo contrast and thrombi in patients with
mitral stenosis and atrial fibrillation.
AB - The purpose of this study was to investigate the independent factors associated
with the presence of left atrial (LA) spontaneous echo contrast (SEC) and
thromboembolic events in patients with mitral stenosis (MS) in chronic atrial
fibrillation (AF). Factors independently associated with LASEC, thrombi, and
embolic events have been mainly investigated in patients with nonvalvular AF or
inhomogeneous populations with rheumatic heart disease. Transesophageal and
transthoracic echo studies were performed in 129 patients with MS in chronic AF.
Previous embolic events were documented in 45 patients, 20 of them within 6
months, and 65 patients were receiving long-term anticoagulation. The intensity
of LASEC and mitral regurgitation, the presence of thrombi and active LA
appendage flow (peak velocities > or = 20 cm/s), and LA volume as well as other
conventional echo-Doppler determinations were investigated in every patient. The
prevalences of significant LASEC (degrees 3+ and 4+), thrombus, active LA
appendage flow, and significant mitral regurgitation (>2+) were: 52% (67
patients), 29.5% (38 patients), 32% (41 patients), and 36% (47 patients),
respectively. Multivariate analysis showed that decreasing mitral regurgitation
severity, absence of active LA appendage flow, and mitral valve area were the
independent correlates of LASEC (odds ratio [OR] 3.7, 5.4, and 0.17,
respectively; all p <0.02). Active LA appendage flow and anticoagulant therapy
were associated negatively, whereas the severity of LASEC was associated
positively with the finding of LA thrombus (OR 9.6, 3.9, and 1.6, respectively;
all p <0.05). The intensity of LASEC and previous anticoagulant therapy (OR 1.74
and 4.5, respectively; p <0.005) were the independent covariates of thrombi
and/or recent embolic events. In conclusion, the severity of mitral regurgitation
and lack of active LA appendage flow were, respectively, the strongest
independent correlates of significant LASEC and thrombus in patients with MS in
chronic AF. LASEC remains the cardiac factor most strongly associated with
thrombus and/or recent embolic events in these patients.
PMID- 11009272
TI - Prevalence and diagnostic value of precordial murmurs for valvular regurgitation
in obese patients treated with dexfenfluramine.
AB - Echocardiography is recommended for the detection of valvular regurgitation in
asymptomatic users of anorexigens with a heart murmur. To determine the
prevalence and diagnostic value of heart murmurs for valvular regurgitation, 223
patients receiving dexfenfluramine therapy for 6.9 months and 189 matched
controls underwent history and cardiac auscultation by experienced
noncardiologists unaware of echocardiography. Color Doppler echocardiograms were
interpreted by 3 observers unaware of patients' clinical data. The frequency of
at least mild regurgitation of any valve and abnormal regurgitation (moderate
mitral or tricuspid or mild aortic regurgitation) were determined. Heart murmurs
heard in 31 dexfenfluramine users (14%) and in 20 controls (11%) were all
systolic and of grade I to II/VI intensity. Mild or worse regurgitation of any
valve showed a trend in patients (18% vs 11.6% in controls, odds ratio [OR] 1.66,
confidence interval [CI] 0.95 to 2.9, p = 0.08), but abnormal regurgitation
(includes Food and Drug Administration grade regurgitation) was more common in
patients (9% vs 3% in controls, OR 3.0, CI 1.18 to 7.65, p = 0.02). In
dexfenfluramine users, heart murmurs were associated with at least mild or
abnormal regurgitation (OR 3.1 and 3.05, 95% CI 1.34 to 7.13 and 1.1 to 8.67; p =
0.008 and 0.036, respectively), had a specificity of 89% and 88%, negative
predictive value of 85% and 93%, but sensitivity of 37% and 30%, and positive
predictive value of 35% and 19%, respectively. Most valves missed by cardiac
auscultation had normal morphology and mild regurgitation. Finally, heart murmurs
had better diagnostic value for either type of valvular regurgitation than heart
murmurs and clinical variables or clinical variables alone. In summary, in
dexfenfluramine users the prevalence of heart murmurs was low and their absence
predicted absence of mild or worse regurgitation of any valve or abnormal
valvular regurgitation. Therefore, cardiac auscultation should be the screening
method of choice for detecting valvular regurgitation in users of anorexigens.
PMID- 11009274
TI - Conclusions from the VA-HIT study.
PMID- 11009273
TI - Evolution of aortic regurgitation following simple patch closure of doubly
committed subarterial ventricular septal defect.
AB - We reviewed the Doppler echocardiographic findings of the aortic valve and
associated aortic regurgitation (AR) in 55 patients who underwent patch closure
of doubly committed subarterial ventricular septal defect (VSD). The maximal
diameter of the VSD measured > or = 5 mm, whereas the postoperative follow-up
interval was > or = 5 years. Twenty-three patients underwent closure before they
developed aortic cusp prolapse or AR (group A). In 15 patients the VSD was closed
when aortic cusp prolapse was recognized, but AR was absent (group B). Aortic
cusp prolapse with AR was detected before closure in a further 15 patients (group
C). Of 8 patients with no AR before closure, AR was detected during follow-up in
6 group A and in 2 group B patients. In group C, AR resolved after surgery in 4
patients, whereas AR grade improved in a further 8 patients and remained
unchanged in 3. Although residual AR was more frequent in patients with aortic
cusp prolapse and AR before closure, it was silent and asymptomatic.
PMID- 11009275
TI - Should the split format in the third position of the pacemaker code be
resurrected?
AB - It is possible to characterize some of the sensing functions of new multisite
pacing systems by resurrecting the split format in the third position of the
standard pacemaker code. This approach permits accurate representation of the
horizontal and vertical triggering functions of multisite dual-chamber pacemakers
without creating a new code.
PMID- 11009276
TI - High-density lipoprotein cholesterol and triglyceride response with simvastatin
versus atorvastatin in familial hypercholesterolemia.
AB - The clinical and biochemical determinants of high-density lipoprotein (HDL) and
triglyceride response to simvastatin and atorvastatin were assessed in 150
patients with severe hyperlipidemia treated in a randomized open-trial format
design. Triglyceride reduction was only dependent on HDL:apolipoprotein A1,
change in apolipoprotein B, and dose response, whereas an increase in HDL was
dependent on initial LDL, change in LDL or dose response, and therapy with
simvastatin.
PMID- 11009277
TI - Effect of probucol on repeat revascularization rate after percutaneous
transluminal coronary angioplasty (from the Probucol Angioplasty Restenosis Trial
[PART]).
AB - To address the issue of whether probucol reduces clinical events after
percutaneous transluminal coronary angioplasty (PTCA), we surveyed clinical
status at 1 year after PTCA of 101 patients who had entered the Probucol
Restenosis Angioplasty Trial. Repeat angioplasty at index lesions were required
in 5 patients in the probucol group and in 12 in the control group, suggesting
that probucol administered beginning 4 weeks before PTCA reduces repeat
revascularization rates for 1 year.
PMID- 11009278
TI - Impact of enoxaparin low molecular weight heparin in patients with Q-wave
myocardial infarction.
AB - A subgroup meta-analysis from the Efficacy and Safety of Subcutaneous Enoxaparin
in Non-Q-Wave Coronary Events (ESSENCE) and the Thrombolysis in Myocardial
Infarction (TIMI) 11B studies has shown that enoxaparin is superior to
unfractionated heparin in reducing the composite end points of death, myocardial
infarction, and emergency revascularization in patients with Q-wave myocardial
infarction. The beneficial treatment effect was significant at 43 days.
PMID- 11009279
TI - Association between heart rate-corrected QT interval and coronary risk factors in
2,894 healthy subjects (the DESIR Study). Data from an Epidemiological Study on
the Insulin Resistance syndrome.
AB - In the prospective Data from an Epidemiological Study on the Insulin Resistance
Syndrome, 2,894 healthy subjects aged 30 to 64 years had determinations of
fasting glucose, insulin, serum lipid and fibrinogen concentrations, blood
pressures, body mass index, and waist-hip ratio, as well as tobacco and alcohol
consumptions and physical activity. A 12-lead electrocardiogram with automatic
measurement of the QT interval was recorded and the formula used for heart rate
correction was based on the best-fit regression between QT and heart rate. The QT
duration was influenced by glucose homeostasis in both sexes, and increased in
men with physical activity; there was a dose-effect relation for men who smoked.
PMID- 11009280
TI - Continuous intravenous diltiazem infusion for short-term ventricular rate control
in children.
AB - Intravenous diltiazem was administered to 10 pediatric patients with primary
atrial tachyarrhythmias with rapid ventricular response. Rapid, consistent, and
safe temporary ventricular rate control was obtained in all patients given this
medication.
PMID- 11009281
TI - Holter monitoring: are two days better than one?
AB - The optimal duration of Holter monitoring (HM) to minimize costs and maximize
yield is unknown. In a retrospective review of 164 patients referred to a
tertiary care center for evaluation with 2 days of HM, we found that 48 hours was
not cost effective when compared with the traditional 24-hour period.
PMID- 11009282
TI - Effect of hypertension on cardiac mass and radial artery wall thickness.
AB - In subjects with essential hypertension, increased cardiac and radial artery mass
are positively associated. The mechanical factor that contributes in the larger
extent to their enhancement is pulse pressure, not mean arterial pressure.
PMID- 11009283
TI - Usefulness of left atrial size in predicting postoperative symptomatic
improvement in patients with aortic stenosis.
AB - Although surgery is highly effective for symptomatic relief in patients with
aortic stenosis, symptoms of congestive heart failure may be still present
postoperatively. This group of patients with aortic stenosis is characterized by
a wide range of left atrial size, which can predict postoperative symptomatic
improvement.
PMID- 11009284
TI - Effects of milrinone on pulmonary gas exchange in catecholamine-dependent heart
failure.
AB - Hemodynamic benefits of milrinone administration are accompanied by adverse
effects on arterial oxygenation in mechanically ventilated patients with end
stage heart failure. Particular attention should be focused on pulmonary gas
exchange variables after initiation of milrinone treatment in the critically ill
patient.
PMID- 11009285
TI - Impact of tissue harmonic imaging on the assessment of rheumatic mitral stenosis.
AB - We examined the effect of tissue harmonic imaging on the echocardiographic
splitability score and valve area measurement of 40 patients with rheumatic
mitral stenosis. Planimetered valve areas were unaffected by the use of harmonic
imaging, but valve scores were increased, particularly in patients with scores
<10.
PMID- 11009286
TI - Mechanism of pulmonary vein stenosis in infants with normally connected veins.
AB - We used microscopy, immunohistochemistry, and cell culture to identify the
mechanism of restenosis in 4 infants with isolated pulmonary vein stenosis.
Recurrent obstruction appears to be due to myofibroblastic proliferation in this
fatal disease.
PMID- 11009287
TI - Six-month success of intracoronary stenting for anomalous coronary arteries
associated with myocardial ischemia.
AB - Fourteen patients with anomalous coronary arteries associated with objective
evidence of myocardial ischemia, a group at increased risk for cardiac events,
were successfully stented. This led to 6-month patency and resolution of the
ischemia, which was confirmed angiographically and by stress imaging studies.
PMID- 11009289
TI - Increased plasma homocysteine is an independent predictor of new atherothrombotic
brain infarction in older persons.
AB - A prospective study investigated the association of plasma homocysteine and other
risk factors with the incidence of atherothrombotic brain infarction (ABI) at 31
+/- 9 month follow-up in 153 men and 347 women (mean age 81 +/- 9 years, median
age 82). The stepwise Cox regression model showed that significant independent
predictors of new ABI in older persons were age (risk ratio 1.060 for each 1-year
increase of age), plasma homocysteine (risk ratio 1.079 for each 1 micromol/L
increase), prior ABI infarction (risk ratio 3.282), current cigarette smoking
(risk ratio 2.687), hypertension (risk ratio 2.965), and diabetes mellitus (risk
ratio 2.015).
PMID- 11009288
TI - Comparison of quinapril versus atenolol: effects on blood pressure and cardiac
mass after renal transplantation.
AB - Based on epidemiologic facts on elevated cardiovascular mortality in renal
allograft recipients, an echocardiographic 2-year follow-up in hypertensive renal
allograft recipients was conducted. This study provides evidence that, in
contrast to atenolol, quinapril, independent of blood pressure reduction, reduces
left ventricular hypertrophy and improves left ventricular diastolic function in
this population.
PMID- 11009290
TI - Effect of shaving the chest of hirsute subjects on transthoracic impedance to
self-adhesive defibrillation electrode pads.
AB - We determined transthoracic impedance (TTI) before and after shaving in 9 hirsute
and 11 nonhirsute subjects. TTI in hirsute subjects was mean +/- SE 162 +/- 11
versus 103 +/- 6 ohms in nonhirsute subjects (p <0.01); TTI decreased to 105 +/-
3 ohms after shaving the hirsute chests (p <0.01).
PMID- 11009291
TI - Postmenopausal smokers show reduced hemodynamic benefit from oral hormone
replacement.
AB - With use of a randomized, placebo-controlled trial, 62 healthy, postmenopausal
smokers and nonsmokers were tested for resting and stress-induced hemodynamic
variables before and after 6 months of treatment with either oral hormone
replacement therapy or placebo. Smokers had significantly less reduction in both
resting and stress-induced vascular resistance and blood pressure after treatment
with oral hormone replacement therapy than nonsmokers.
PMID- 11009292
TI - Statins, high-density lipoprotein, and the low-density lipoprotein/high-density
lipoprotein ratio.
PMID- 11009293
TI - Pediatric radiologists: who we are and what we do. Results of a membership survey
of the Society for Pediatric Radiology--1999.
AB - BACKGROUND: There is a need for reliable monitoring of workforce trends in the
field of pediatric radiology by the Society for Pediatric Radiology. In addition,
the Society should periodically assess itself as to its mission and relevance to
its members via membership surveys. OBJECTIVE: The Membership Committee of the
Society for Pediatric Radiology, 1999, conducted a 54-question survey to
determine the makeup of its members, job profiles, satisfaction with services of
the Society for Pediatric Radiology, and its official journal, Pediatric
Radiology. MATERIALS AND METHODS: Seven hundred fifty surveys were given to
active members of the Society for Pediatric Radiology in the United States and
Canada. There were 275 surveys returned for an overall response of 37%. RESULTS:
Mean age of members is 48 years with 99% of respondents working. Membership is
34% female and 66% male. Women members of the Society are younger (45 vs 49
years, P = 0.0012) and work less hours (47.8 vs 51.0, P = 0.0135) than men. Fifty
seven percent of respondents practice in a freestanding children's hospital, 29%
in a "children's hospital within a hospital," and 14% are in community hospitals
or an office-based practice. Eighty-two percent of the responding pediatric
radiologist's time is spent in performing examination on children, with only 18%
spent on adult work or administration. Forty-eight percent work at more than one
office. Sixty-one percent worked evenings or weekends, excluding night call. Two
hundred twenty-two of 275 respondents had received a Certificate of Added
Qualification. The meeting "for CME credit" was considered the most important
benefit of Society membership. Most respondents read select articles in Pediatric
Radiology. There was sentiment to decrease esoteric case reports in favor of
review articles. Only 19% of respondents submitted their articles to Pediatric
Radiology initially. CONCLUSION: Pediatric radiologists are a diverse membership
with the common goal of advocating for healthcare and imaging in children. Survey
information given to the leadership of the Society will help the organization
remain responsive to its members.
PMID- 11009294
TI - What is the normal prevalence of vesicoureteral reflux?
AB - BACKGROUND: The prevalence of vesicoureteral reflux in normal children has been
estimated to be 0.4% to 1.8%. Based on epidemiological data, it can be estimated
that 2.2% of girls and 0.6% of boys may be found to have reflux as a result of
the investigation of urinary tract infection. This implies that most children
with reflux will develop urinary tract infection. However, most children with
reflux detected by screening do not develop infection. Hence the prevalence of
vesicoureteral reflux in normal children may be higher than the previous
estimates. OBJECTIVE: To determine the prevalence of vesicoureteral reflux in
groups of children with different clinical indications for cystogram. MATERIALS
AND METHODS: Over 250 articles from the literature were reviewed to determine the
prevalence of vesicoureteral reflux in children undergoing cystogram. Means and
95% confidence limits were derived from the data in studies that met the
inclusion criteria. RESULTS: The prevalence of vesicoureteral reflux in children
with urinary tract infection was 31.1% (95% CI: 29.9-32.8). The prevalence of
vesicoureteral reflux varied between patient groups, but often approached or
exceeded the prevalence in urinary tract infection. The prevalence in normal
kidneys was 17.2% (95% CI: 14.4-20.1). CONCLUSION: Vesicoureteral reflux is
common in nearly all patient groups examined. The prevalence of vesicoureteral
reflux in normal children is probably significantly higher than the traditional
estimates.
PMID- 11009295
TI - The impact of imaging in the management of intussusception owing to pathologic
lead points in children. A review of 43 cases.
AB - OBJECTIVE: To review the imaging appearances, management and outcome of a large
number of children with intussusception owing to pathologic lead points (PLP) in
an attempt to define the role of various imaging modalities in this clinical
setting. MATERIALS AND METHODS: Review of the records and imaging studies of 43
children with intussusception due to PLP diagnosed between 1986 and 1999.
RESULTS: The commonest PLP found were Meckel diverticulum, polyps, Henoch
Schonlein purpura and cystic fibrosis. PLP were depicted on sonography in 23
(66%) of 35 patients, on computed tomography in 5 (71%) of 7, on air enema in 3
(11%) of 28, and on barium enema in 6 (40%) of 15. Air enema successfully reduced
60% of the intussusceptions. Nine children had recurrent intussusceptions.
CONCLUSION: Sonography depicted two-thirds of PLP and provided a specific
diagnosis in nearly one-third of our series. Our review does not provide
sufficient data on how to continue the investigation of those patients in whom
sonography does not depict a PLP but in whom there is a high index of suspicion
for its presence. It remains a diagnostic challenge as to how to search for PLP
in these patients, and other imaging modalities have to be requested according to
each particular case.
PMID- 11009296
TI - Aneurysmal dilatation of the paraumbilical vein in an infant.
AB - The paraumbilical veins are one of the most common collateral pathways developing
in portal hypertension. Aneurysmal dilatation of a patent paraumbilical vein is a
very unusual finding. We report the first infant case of a paraumbilical vein
aneurysm and its Doppler ultrasound findings.
PMID- 11009297
TI - Transvenous coil embolization of an extrahepatic portosystemic shunt in a dog: a
naturally occurring model of portosystemic malformations in humans.
AB - Congenital patent ductus venosus (PDV) occurs far more commonly in dogs than in
people; consequently, the natural course of the disease in dogs was studied as a
model to understand the pathophysiology behind the vascular anomaly and its
response to therapy better. In this report, the authors describe the results of
percutaneous coil embolization as a single procedure in a dog with a single
congenital extrahepatic portocaval shunt and compare portosystemic vascular
anomalies (PSVA) seen in dogs with those seen in children.
PMID- 11009298
TI - Pancreatic pseudotumor in an 11-year-old child: imaging findings.
AB - BACKGROUND: An inflammatory pseudotumor is a benign, solid lesion of unclear
etiology. Some authors believe it is a true neoplasm, while others consider it a
post-infectious or post-traumatic process. It is most commonly found in the lung;
an inflammatory pseudotumor of the pancreas is rare. This case report is the
sixth of a pancreatic pseudotumor in a child. PATIENTS AND METHODS: An 11-year
old girl presented with obstructive jaundice due to a mass in the head of the
pancreas. The mass was identified by sonography. This was confirmed by MRI and
CT. The mass enhanced with gadolinium, but its enhancement at CT was similar to
the remainder of the pancreas. RESULTS: At operation, a pancreatic inflammatory
pseudotumor was totally resected.
PMID- 11009299
TI - Further report of small-bowel intussusceptions related to gastrojejunostomy
tubes.
AB - BACKGROUND: The use of gastrojejunostomy (GJ) tubes for feeding pediatric
patients who have inadequate oral intake, cannot tolerate gastric feeding, or
have significant gastroesophageal reflux may present problems. OBJECTIVE: To
report our experience of intussusception associated with GJ tubes, with emphasis
on risk factors. MATERIALS AND METHODS: Clinical histories and imaging studies
were reviewed for all patients with GJ tube-associated intussusceptions at our
institution from January 1995 to March 1999. RESULTS: Of 251 GJ tubes inserted,
40 (16%) intussusceptions occurred in 30 patients (20 males). They ranged in age
from 3 months to 17 years (mean 2.6 years) and in weight from 3 to 90 kg (mean
12.5 kg). The underlying diagnosis varied. The main symptom was bilious vomiting.
The initial diagnosis was made by sonography in 19 cases and fluoroscopy in 21.
Intussusceptions recurred eight times in patients with a distal pigtail (n = 17)
but only twice in patients without the distal pigtail (n = 18). CONCLUSIONS: GJ
tube related intussusception is a common, easily diagnosed problem. Predisposing
factors appear to be male sex, young children, and presence of a distal pigtail
on the tube. Awareness of intussusception is imperative for prompt diagnosis to
achieve feeding tolerance.
PMID- 11009300
TI - Intracranial resistive index (RI) values in normal term infants during the first
day of life.
AB - PURPOSE: The purpose of this study was to determine normal resistive index (RI)
values for term neonates during the first day of life as part of an ongoing
prospective study of RI values in term infants with perinatal asphyxia. MATERIALS
AND METHODS: Forty normal term neonates underwent cranial sonography and Doppler
during the first 24 h after birth. Transfontanelle Doppler was performed of the
internal carotid, anterior cerebral, and middle cerebral arteries bilaterally. In
addition, transtemporal Doppler was performed of the middle cerebral arteries
bilaterally. Mean and median RI values were calculated in all vessels
interrogated. The transfontanelle and transtemporal middle cerebral artery
measurements were compared using paired t-tests. RESULTS: The overall mean RI of
all interrogated vessels was 0.726 with a standard deviation of 0.057. The mean
RI value in the middle cerebral arteries was not significantly different with the
two different measurement techniques. CONCLUSION: Normal intracranial RI values
for a term infant in the first day of life were calculated for comparison with RI
values in term infants with perinatal asphyxia.
PMID- 11009301
TI - MR spectroscopic imaging of normal-appearing white matter in
adrenoleukodystrophy.
AB - BACKGROUND: Adrenoleukodystrophy (ALD) is characterised by wide phenotypic
variation, and there is no marker to predict the onset of cerebral demyelination.
The indications for therapeutic approaches depend largely on the onset of
cerebral demyelination. OBJECTIVE: To evaluate the brain spectroscopic pattern in
normal-appearing white matter (NAWM) in patients with various phenotypes of ALD
to determine if these abnormalities could be of useful prognostic value.
MATERIALS AND METHODS: Spectroscopic imaging acquisition mode (MRSI, 16 x 16
voxels) was performed in 20 patients with ALD, including 7 neurologically
asymptomatic patients without detectable demyelination on MRI, 3 patients with
early signs of cerebral demyelination, 8 patients with adrenomyeloneuropathy
(AMN) and 2 patients with cerebral ALD who had previously undergone bone marrow
transplantation. Controls were 22 healthy subjects. In all patients, four voxels
entirely located in the juxtaventricular NAWM were studied. The ratios NAA/Cho,
NAA/ CPC and Cho/CPC for the four ROIs were measured in the patient population
and compared with control values. Results. In spite of a large distribution of
ratios, the statistical tests did not show any significant difference between the
ratios within NAWM in the patient population compared with control values. Means
of ratios in the left posterior (LP) voxel compared normal subjects were (a) in
neurologically asymptomatic ALD patients (n = 7) 2.27 +/- 0.63 for NAA/CPC, 2.21
+/- 0.75 for NAA/ Cho, 1.06 +/- 0.28 for Cho/CPC, (b) in patients with early
signs of demyelination (n = 3) 3.43 +/- 0.85 for NAA/ CPC, 2.47 +/- 0.32 for
NAA/Cho, 1.37 +/- 0.16 for Cho/CPC and (c) in AMN patients (n = 8) 1.47 +/- 0.53
for NAA/CPC, 2.17 +/- 1.58 for NAA/ Cho, 0.83 +/- 0.32 for Cho/CPC. Conclusions.
The study did not show significant differences in metabolite ratios between
patients and controls. The large distribution of results precludes the
possibility of detecting small variations. Part of this distribution can be due
to the CSI method. Longitudinal spectroscopic studies, preferentially using
monovoxel spectroscopy, are clearly needed.
PMID- 11009302
TI - Intrauterine subdural hematoma.
AB - A patient with neonatal macrocephaly due to bilateral chronic subdural hematoma
is presented. There was no history of intrauterine trauma or coagulopathy. Such
patients are apparently rare. The pathogenesis of intrauterine chronic subdural
hematoma in such patients is unclear.
PMID- 11009303
TI - CT-guided radiolabelled aerosol studies for assessing pulmonary impairment in
children with bronchiectasis.
AB - OBJECTIVE: To determine whether CT-guided mucociliary clearance studies allow
differentiation between bronchiectasis associated with primary ciliary dyskinesia
(PCD) and those unrelated to congenital or genetically transmitted defects.
MATERIALS AND METHODS: Fifteen children aged 4-18 years with a CT diagnosis of
bronchiectasis were included in the study. Six had PCD, while in nine cases no
congenital disorder was demonstrated. RESULTS: CT showed bronchiectasis in 26
(29%) of 90 lung regions. Radiolabelled aerosol studies were conducted globally
for each lung and on the regions affected by bronchiectasis. Global half-time of
activity (t 1/2) values of patients with PCD were significantly higher (P <
0.001) than those with bronchiectasis unrelated to congenital disorders. Among
the 26 lung regions in which CT demonstrated bronchiectasis, regional clearance
was abnormal in 24 cases. Patients with PCD showed no statistically significant
difference between regional and global t 1/2 values. Patients with bronchiectasis
unrelated to congenital disorders showed significantly higher regional t 1/2
values in the affected regions with respect to the corresponding global pulmonary
t 1/2 (P < 0.06). CONCLUSIONS: The combination of morphological CT information
with functional data concerning the clearance of radiolabelled aerosol adds to
our understanding of pulmonary impairment in children with bronchiectasis. In
particular, regional studies allow the recognition of different mucociliary
clearance patterns in bronchiectasis associated with PCD and those unrelated to
congenital or genetically transmitted defects.
PMID- 11009304
TI - MR imaging of pentalogy of Cantrell variant with an intact diaphragm and
pericardium.
AB - We present a case of a neonate with the stigmata for pentalogy of Cantrell with
the exception of diaphragmatic and pericardial defects. Diagnosing most of the
anomalies in this rare syndrome can be accomplished using conventional modalities
in radiology, but difficulties may arise determining diaphragmatic continuity.
Accurate, early diagnosis of components of this syndrome is vital for surgical
planning and assessing prognostic factors.
PMID- 11009305
TI - Regional lymphadenopathy in cat-scratch disease: ultrasonographic findings.
AB - BACKGROUND: Cat-scratch disease (CSD) is considered to be an emerging disease
worldwide and is caused by Bartonella henselae, a gram-negative bacterium
introduced by a scratch or bite of a cat. The most common clinical manifestation
is regional lymphadenopathy, but clinical recognition may be difficult, as
atypical manifestations may occur. The diagnosis is confirmed with serologic
testing and histology is rarely needed. This paper is based on our experience
with the use of ultrasonography in the diagnosis of CSD. OBJECTIVE: The aim of
this study was to describe the sonographic and color Doppler appearances of
regional lymphadenopathy in CSD, as this has not widely reported in the
literature. MATERIALS AND METHODS: Forty-seven patients (average 9.4 years) were
included who all had serologically and/or histologically proven CSD and had been
studied using US early in the clinical course. All had a positive history of
exposure to cats and exhibited regional lymphadenopathy. RESULTS: US showed large
hypoechoic adenopathy with some transmission enhancement and high vascularization
on color-flow Doppler imaging. In 30 patients, abdominal US was also performed
and splenic and/or hepatic granulomata were found in 10. CONCLUSIONS: In our
experience, sonography and especially color-Doppler and power-Doppler sonography
was helpful in the diagnosis of CSD. We believe it should be used in the initial
study of children with regional lymphadenopathy, and serologic testing should be
performed when CSD is suspected.
PMID- 11009306
TI - Cephaloskeletal dysplasia (Taybi-Linder syndrome: osteodysplastic primordial
dwarfism type III): report of two cases and review of the literature.
AB - We report two unrelated infants with cephaloskeletal dysplasia or Taybi-Linder
syndrome, also referred to as osteodysplastic primordial dwarfism Type III. They
presented with peculiar facial features, microcephaly and skeletal and cerebral
abnormalities documented radiographically and with cranial MRI and/or CT. Some
dissimilarities were observed in the skeletal findings between the two patients,
most likely reflecting phenotypic variability within the same disorder. Some
radiographic features were shown to evolve with time in both patients. Also of
interest is the unusually long survival of these patients, more than 4 years in
the first and of over 6 years in the second.
PMID- 11009307
TI - Feeding intolerance secondary to marked hepatosplenomegaly compressing the
stomach in children.
PMID- 11009308
TI - The role of sonography in children with abdominal pain after recent successful
reduction of intussusception.
PMID- 11009309
TI - Teratoid Wilms' tumour occurring synchronously with classical Wilms' tumour in
Beckwith Wiedemann syndrome.
PMID- 11009310
TI - The twenty-five-year history of the Castroviejo Cornea Society.
PMID- 11009311
TI - Ramon Castroviejo 1904-1987.
PMID- 11009312
TI - Techniques in penetrating keratoplasty: a quarter century of development.
PMID- 11009313
TI - The evolution of lamellar grafting techniques over twenty-five years.
AB - The history of lamellar keratoplasty (LK) surgery spans over 100 years, and the
advantages of lamellar surgery have long been known. The surgery is usually used
for tectonic purposes; however, new techniques and technology over the past 25
years have expanded the applications of LK in optical rehabilitation.
Instrumentation such as viscoelastics, diamond knives, ultrasonic pachymetry,
artificial anterior chambers, advanced microkeratomes, and the excimer laser have
enhanced our ability to work more safely in the tedious microsurgical environment
of the lamellar procedure. Advances in surgical techniques such as deep lamellar
anterior keratoplasty and deep lamellar endothelial keratoplasty have expanded
the application of lamellar surgery to endothelial replacement and have achieved
visual results approaching those of penetrating keratoplasty while reducing the
rate of rejection and improving the long-term graft stability. As research
continues, LK promises to be an increasingly important option for the corneal
surgeon.
PMID- 11009314
TI - The management of corneal trauma: advances in the past twenty-five years.
AB - Over the past quarter century, advances in our understanding of corneal anatomy,
physiology, and wound healing have all played an integral role in the management
of corneal trauma. As the etiologies of corneal trauma have changed, so has our
understanding of the impact of injury on corneal function as it relates to visual
rehabilitation. Numerous new classes of antibiotics, antiinflammatory agents, and
tissue adhesives have emerged. Occlusive therapy has advanced from simple
pressure patching bandage soft contact lenses and collagen shields. Surgical
instrumentation, operating microscopes, viscoelastic substances, and suture
materials have all improved the outcomes of corneal trauma repair. Improved
understanding of the refractive properties of the cornea through topography and
alternative suture techniques has helped us restore the natural corneal curvature
and visual outcomes. Consequently, in the last quarter of this century our
therapeutic approaches to cornea trauma, both medical and surgical, have
improved.
PMID- 11009315
TI - Twenty-five-year panorama of corneal immunology: emerging concepts in the
immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and
corneal transplant rejection.
AB - PURPOSE: To describe the most recent advances in our understanding of the
cellular and molecular mechanisms involved in the immunopathogenesis of corneal
immunoinflammatory disorders including microbial keratitis, peripheral ulcerative
keratitis. and allograft rejection. METHODS: Review of the published peer
reviewed literature that has contributed significantly to our modern
understanding of corneal immunology. In addition, the authors have summarized the
information in conceptual diagrams that highlight the critical cellular and
molecular pathways that lead to corneal immune responses in the two most
thoroughly studied corneal immune disorders, herpes simplex keratitis (HSK) and
transplant rejection. RESULTS: In spite of the wide array of molecular and
cellular factors that mediate corneal immunity, critical mechanistic facets are
shared by the various corneal immunoinflammatory disorders. These include
activation and migration of local antigen-presenting cells (APCs), including
Langerhans cells (LCs), upregulation in pleiotropic proinflammatory cytokines
such as interleukin-1 (IL-1) and tumor necrosis factor-alfa (TNF-alpha) that can
mediate a wide array of immune functions in addition to up-regulating protease
expression. and chemokines that play a critical role on the one hand in
attracting nonantigen-specific inflammatory cells such as neutrophils and on the
other in attracting CD4+ T helper type 1 (Th1) cells that mediate most of the
destruction in the cornea. CONCLUSIONS: In the last 25 years, we have seen our
field develop from a descriptive stage into a new phase where the fundamental
processes that mediate and effect corneal immunity are being accurately
deciphered. It is anticipated that this new knowledge will allow development of
specific molecular and genetic therapeutic strategies that could target critical
steps in the immunopathogenesis of disease without the untoward side-effects of
nonspecific generalized immune suppression that still remains the standard of
care today.
PMID- 11009316
TI - The diagnosis and management of dry eye: a twenty-five-year review.
AB - PURPOSE: To review the advances in the diagnosis, pathogenesis, and management of
dry eye disease in the past 25 years. METHODS: Literature review. RESULTS: The
preocular tear film is a hydrated mucus gel that contains soluble antimicrobial
proteins and growth factors that protect and support the ocular surface. The
final common pathway in dry eye is a perturbation of the integrated ocular
surface/lacrimal gland reflex unit. Diagnostic tests evaluating tear composition
and clearance appear to show stronger correlation with the severity of ocular
irritation symptoms and keratoconjunctivitis sicca (KCS) than the conventional
Schirmer tests. KCS is a condition of abnormal differentiation and mucus
production by the ocular surface epithelium that results in a poorly lubricated,
abnormally permeable ocular surface that has increased susceptibility to
environmental insults. Chronic subclinical ocular surface inflammation appears to
play a key role in the pathogenesis of KCS. New therapeutic strategies are aimed
at reducing the ocular surface inflammation of dry eye disease. CONCLUSIONS:
There has been a tremendous increase in knowledge regarding dry eye disease in
the past 25 years that has resulted in improved diagnostic classification and new
targeted therapies.
PMID- 11009317
TI - Changing concepts in the diagnosis and management of blepharitis.
AB - PURPOSE: Chronic blepharitis is one of the most common conditions seen in the
ophthalmologist's office; but, it is difficult to treat effectively.
Nevertheless, much progress has been made over the last quarter century, not only
in diagnosis but also in treatment of blepharitis. METHODS: Perhaps the most
important progress has been made as the result of extensive and detailed clinical
evaluations of patients, sometimes over extended periods of time with diverse
patient populations. RESULTS: The availability of sophisticated instrumentation
and laboratory techniques, as well as an array of antibiotics, has enhanced the
whole picture for effective blepharitis treatment. CONCLUSION: Although much
progress has been made, it is important to build on the present understanding.
Most important is the continued development of targeted treatment protocols that
address specific signs, as is now possible with microbial abnormalities. Progress
in the understanding and treatment of relevant inflammatory processes will
benefit from continuing biomedical discoveries.
PMID- 11009318
TI - The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis:
1970-2000.
AB - The editors of this Festschrift asked us to review the use of antibiotics for the
treatment of bacterial conjunctivitis and keratitis over the past 25 years, a
period coinciding with the life of the Castroviejo Corneal Society. We believe it
is more appropriate to begin our review in the late 1960s. about the time that
experimental and clinical studies and algorithms for the clinical care derived
from these studies helped shape a more rigorous approach to therapy. Those years
saw the introduction of antibiotics that were adapted for ophthalmic use, many of
which are still being used today. We will give more weight to our review of
keratitis than conjunctivitis.
PMID- 11009319
TI - The evolution of antiviral therapy for external ocular viral infections over
twenty-five years.
AB - PURPOSE: To review the past 25 years of the evolution of antiviral therapy for
the treatment of common external ocular viral infections (herpes simplex virus
type 1, varicella-zoster virus, and adenovirus). METHODS: A broad-based
literature review in the fields of virology, antiviral research, and
ophthalmology will be carried out. The pathogenesis of the major external ocular
viral infections and history of antiviral development will be cited. Important
conceptual breakthroughs as well as historical landmarks will be emphasized.
RESULTS: The successful development of effective antivirals to treat the most
common external ocular viral infections have dramatically reduced morbidity and
sight loss. The immune pathogenesis of herpetic stromal keratitis is better
understood. CONCLUSIONS: Remarkable progress in the development of antiviral
therapy has occurred over the past quarter century. Future needs include improved
antivirals and immunomodulators and vaccines to prevent and treat herpetic ocular
infections and adenovirus keratoconjunctivitis.
PMID- 11009320
TI - Advances in the management of keratomycosis and Acanthamoeba keratitis.
AB - PURPOSE: In the late 1960s, the management of fungal keratitis was a serious
unresolved problem. Little was known of the epidemiology of the disease, and
there were no antifungal agents formulated for use in the eye. METHODS: A
thorough review of the literature was done back to 1969 on clinical reports and
experimental studies for keratomycosis and Acanthamoeba keratitis. RESULTS: Since
1969, through basic and clinical research, the epidemiology of the disease
worldwide is better understood. One new topical antifungal agent, natamycin, with
efficacy against filamentous fungi has been developed and the pharmacokinetics of
topically applied antifungal drops have been explored. Progress has been slow but
the prognosis for keratomycosis has immeasurably improved over the period.
Acanthamoeba was first recognized as an ocular pathogen in 1973 and was the cause
of an epidemic in the 1980s caused by contaminated contact lens, although other
risk factors were also identified. At the onset of the epidemic, there was no
known treatment. but as a result of intense research efforts, within a few years
a well-defined therapeutic approach had been developed that had a significant
impact on the prognosis for this initially devastating infection. For both
infections, the role of corticosteroids for controlling the inflammation remains
controversial, but the place for keratoplasty is now well defined. CONCLUSIONS:
Although there has been steady progress in the management of both infections,
continued research is the way to define more effective medical and surgical
therapy.
PMID- 11009321
TI - Changing concepts in the management of severe ocular surface disease over twenty
five years.
PMID- 11009322
TI - Genetics of the corneal dystrophies: what we have learned in the past twenty-five
years.
AB - PURPOSE: To indicate important changes in our understanding of the corneal
dystrophies. METHODS: A review of the literature of the last quarter of a
century. RESULTS: The earliest clinical classifications of the corneal
dystrophies were based on the application of clinical, biological, histochemical,
and ultrastructural methods. Since then, the first great impetus to our
understanding has come from the application of techniques to map disorders to
specific chromosome loci, using polymorphic markers. More recently, using
candidate gene and related approaches, it has been possible to identify genes
causing several of the corneal dystrophies and the mutations responsible for
their phenotypic variation. A notable success has been to show that several
important "stromal" dystrophies result from mutations in the gene beta ig-h3,
which encodes for the protein keratoepithelin (beta ig-h3). CONCLUSIONS: For the
corneal dystrophies, as with other inherited disorders, there is room for two
sorts of classification system, one based mainly on clinical presentation and the
other on an up-to-date understanding of the genetic mechanisms. They are not
mutually exclusive. Some developmental corneal disorders are also discussed.
PMID- 11009324
TI - Corneal topography and the new wave.
PMID- 11009323
TI - Specular microscopy, confocal microscopy, and ultrasound biomicroscopy:
diagnostic tools of the past quarter century.
AB - PURPOSE: To identify, characterize, and illustrate the most important past and
future potential contributions of specular, confocal, and ultrasound
biomicroscopy to clinical diagnosis and research applications in the cornea from
the past 25 years. METHODS: Specular microscopy, in vivo tandem scanning confocal
microscopy (TSCM), scanning slit confocal microscopy (SSCM), and high-frequency
ultrasound biomicroscopy are examined. RESULTS AND CONCLUSIONS: This review
demonstrates the abilities and limitations of three powerful new in vivo imaging
modalities to resolve the cellular and structural layers of the cornea temporally
and spatially in three or four dimensions, (x, y, z, t). Clinical pathological
processes such as inflammation. infection, wound healing, toxicity, embryonic
development, differentiation, and disease, which previously could be studied only
under static ex vivo conditions, can now be dynamically evaluated over time.
Thus, with continued development and application in vivo, noninvasive microscopic
techniques should provide exciting new insights into understanding the structure
and function of not only the eye, but also other multicellular organ systems in
health and disease. These new imaging paradigms are in the first rank of advances
in medical science in the past quarter century.
PMID- 11009325
TI - Twenty-five years of contact lenses: the impact on the cornea and ophthalmic
practice.
AB - PURPOSE: The history of contact lenses has occurred in the latter half of the
20th century. In particular, events in the 1970s through the 1980s related to the
invention of soft, hydrogel contact lenses have revolutionized the contact lens
industry and the eye care attached to it. This article recounts that history from
the perspective of market forces, inventions, and discoveries about the
physiologic functioning of the cornea. METHODS: The relevant literature is
critically reviewed. RESULTS: Discoveries about the oxygen needs of the cornea
and consumer pressure for clear, comfortable, around-the-clock vision have
resulted in a history of rigid gas permeable and soft lenses that leads to
today's contact lens picture. The short-term and long-term effects of chronic
hypoxia and the levels of lens oxygen transmissibility necessary to avoid them
have been well-described. The advent of the soft lens, followed by the "human
experiment" with initial extended-wear modalities, led to the advent of the
disposable soft contact lens. CONCLUSIONS: In the past 25 years, the development
and wide acceptance of soft contact lenses have revolutionized the management of
refractive error and corneal diseases.
PMID- 11009326
TI - Advances in refractive surgery: 1975 to the present.
AB - PURPOSE: To review the major advances in the field of refractive surgery
occurring over the past 25 years. METHODS: Literature review. RESULTS: The major
developments in refractive surgery over the past 25 years are reviewed.
CONCLUSIONS: The past 25 years have witnessed great changes in refractive
surgery. As a result of advancements in technology, instrumentation, and
technique, we have seen improvements in the treatment of all types of ametropias.
In this article, we review some of the successes and failures of the past quarter
century.
PMID- 11009327
TI - The past twenty-five years in eye banking.
AB - PURPOSE: This review of milestones and challenges in eye banking describes
efforts made by dedicated eye bankers to ensure the quality and quantity of
corneal tissue for corneal blind patients over the last 25 years. METHODS: This
account is the result of the recollection of the author, discussions with eye
bankers, and a review of the literature, public documents, and Eye Bank
Association of America (EBAA) records. RESULTS: A measure of the success of eye
banking is the fact that corneal transplant surgery is now scheduled as an
elective procedure. Corneal tissue has also enjoyed a stellar safety record. This
is due in part to the establishment of comprehensive medical standards by the
EBAA, the accreditation of eye banks, and the training and certification of eye
bank technicians. CONCLUSION: Advancements in eye banking over the last 25 years
have improved the quality of life of several hundred thousand corneal blind
persons in this country. More efforts must be made in the future to eliminate
corneal blindness internationally.
PMID- 11009328
TI - Temperament and character in women with anorexia nervosa.
AB - The present study examined temperament differences among anorexia nervosa (AN)
subtypes and community controls, as well as the effect of body weight on
personality traits in women with AN. Temperament and Character Inventory (TCI)
scores were compared between 146 women with restrictor-type AN (RAN), 117 women
with purging-type AN (PAN), 60 women with binge/purge-type AN (BAN), and 827
community control women (CW) obtained from an archival normative database. Women
with AN scored significantly higher on harm avoidance and significantly lower on
cooperativeness than CW. Subtype analyses revealed that women with RAN and PAN
reported the lowest novelty seeking, RAN women the highest persistence and self
directedness, and PAN women the highest harm avoidance. Body mass index had a
nominal effect on subgroup differences, suggesting that personality disturbances
are independent of body weight. Findings suggest that certain facets of
temperament differ markedly between women with AN, regardless of diagnostic
subtype, and controls. More subtle temperament and character differences that
were independent of body weight emerged that distinguish among subtypes of AN.
PMID- 11009329
TI - Chronic fatigue syndrome: occupation, medical utilization, and subtypes in a
community-based sample.
AB - Most studies of chronic fatigue syndrome (CFS) have been based on patients
recruited from primary or tertiary care settings. Patients from such settings
might not be typical of patients in the general population. The present
investigation involved examining individuals with CFS from a community-based
study. A random sample of 18,675 respondents in Chicago was first interviewed by
telephone. A group of individuals with chronic fatigue accompanied by at least
four minor symptoms associated with CFS were given medical and psychiatric
examinations. From this sample, a physician review group diagnosed individuals
with CFS. Those diagnosed with CFS were subclassified based on a variety of
categories, including duration of illness, mode of illness onset, and presence or
absence of a stressful life event directly preceding onset. In addition, we
examined medical utilization among those diagnosed with CFS, as well as whether
individuals with CFS were disproportionately represented in health care
professions. Important differences emerged on measures of sociodemographics,
symptoms, and functional disability. The implications of these findings and
others are discussed.
PMID- 11009330
TI - High risk model of threat perception in chronic pain patients: implications for
primary care and chronic pain programs.
AB - This study investigated the High Risk Model of Threat Perception (HRMTP) in
middle-aged, urban chronic pain patients who had been referred to a secondary
pain clinic after failing to respond to standard medical management.
Relationships among absorption, social desirability (SD), and negative (e.g.,
depressive or anxious) affect were studied in 24 male and 73 female patients,
(age range 22-88 years). Subjects completed the Tellegen Absorption Scale, the
Marlowe-Crowne Social Desirability Scale, the Beck Depression Inventory--Second
Edition, and the Beck Anxiety Inventory. The sample was significantly higher in
SD and lower in absorption than normative groups. High SD patients endorsed
significantly fewer items related to depression than those with low SD, but
reported anxious ideation at about the same rate. These findings lend credence to
the concept of chronic pain as a transduction of depressive, but not anxious,
affect into somatic symptoms.
PMID- 11009331
TI - Informativeness of structured diagnostic interviews in the identification of
Tourette's disorder in referred youth.
AB - Although specialized programs have greatly advanced the treatment of youth with
Tourette's disorder (TD), not all children with TD reach such programs, raising
questions as to whether TD is adequately identified outside specialized settings.
There is thus a need for evidence that cases identified in the nonspecialty
setting are "true cases." Because structured diagnostic interview methodology can
reduce errors of omission, this approach can facilitate the identification of TD
in referred youth outside specialized programs. Similarities between cases
ascertained in specialty and nonspecialty settings would suggest that those
identified in the nonspecialty setting were indeed "true cases." Comparisons were
made between youth with TD ascertained through a specialized TD program who had
both a structured diagnostic interview-derived diagnosis of TD plus an expert
evaluation of TD (N = 103), with youth ascertained through a non-TD specialized
pediatric psychopharmacology program who had a structured diagnostic interview
derived diagnosis of TD (N = 92). Irrespective of ascertainment source, children
with structured interview-derived diagnosis of TD shared similar correlates in
terms of tic severity, mean age of onset and duration of tics, as well as
patterns of comorbidity well known to be associated with TD in clinical samples.
Children meeting diagnostic criteria for TD on structured diagnostic interviews
share similarities and patterns of clinical correlates, irrespective of
ascertainment through a specialized TD or non-TD specialized clinic. These
findings support the usefulness of structured diagnostic interview methodology as
a diagnostic aid for the identification of TD in non-TD specialized settings and
facilitate delineation of patterns of comorbidity.
PMID- 11009332
TI - A comparison of posttraumatic stress disorder with and without borderline
personality disorder among women with a history of childhood sexual abuse:
etiological and clinical characteristics.
AB - The overlap in definition and presentation between posttraumatic stress disorder
(PTSD) and borderline personality disorder (BPD) has raised questions about the
relationship of these disorders. Are they separate disorders, variants of the
same disorder, or comorbid conditions? The present study examined etiological
variables and current functioning among two groups of outpatient women with a
history of childhood sexual abuse: those with PTSD only (N = 45) and those with
PTSD and BPD (N = 26). The groups did not differ in severity, frequency, or
number of perpetrators of their childhood sexual abuse, or whether the
perpetrator was a family member or not. The additional diagnosis of BPD was
associated with earlier age of abuse onset and significantly higher rates of
physical and verbal abuse by mother. Severity and frequency of PTSD symptoms were
not affected by BPD diagnosis, suggesting that the personality disorder and PTSD
are independent symptom constructs. The PTSD+BPD group scored higher on several
other clinical measures including anger, dissociation, anxiety, and interpersonal
problems. They did not differ in their frequency of use of mental health services
but tended to be less compliant in their treatment. These and other findings are
discussed, and implications for treatment are considered.
PMID- 11009333
TI - Childhood emotional trauma and chronic posttraumatic stress disorder in adult
outpatients with treatment-resistant depression.
AB - The intent of this study was to test the hypothesis that patients with treatment
resistant depression are more likely than treatment responsive patients to suffer
from sequelae of childhood trauma that may perpetuate depression despite adequate
medication treatment. Twenty participants with treatment-resistant depression and
20 participants with treatment-responsive depression were administered a
structured interview and a battery of psychological tests to assess levels of
current depression, confirm diagnosis, and quantify childhood trauma and presence
of dissociative phenomena. Tests used include the Beck Depression Inventory, the
Mini International Neuropsychiatric Interview, the Minnesota Multiphasic
Personality Inventory-2, the Childhood Trauma Questionnaire, and the Trauma
Symptom Inventory. Compared with treatment responders, the treatment-resistant
participants were significantly more depressed, had significantly more comorbid
anxiety disorders, reported significantly greater levels of childhood emotional
abuse, and experienced current-day sequelae of childhood emotional abuse. The
hypothesis was partially supported by these results. This study suggests that
reported history of childhood emotional abuse and sequelae of that abuse may be
associated with treatment resistance in depressed outpatients.
PMID- 11009334
TI - Memory for acute stress disorder symptoms: a two-year prospective study.
AB - The present study aimed to index the accuracy of memory for acute trauma symptoms
by comparing the symptoms reported by motor vehicle accident (MVA) victims within
1 month posttrauma with the recall of these symptoms at 2 years posttrauma.
Ninety-two consecutive MVA admissions were assessed for the presence of acute
stress disorder (ASD) within 1 month posttrauma. At 2 years posttrauma, 61% (N =
56) of the sample were reassessed for posttraumatic stress disorder (PTSD) and
for accuracy of recall of the symptoms reported during the first assessment. At
least one of the four ASD diagnostic clusters was recalled inaccurately by 75% of
patients. High levels of posttraumatic stress severity and high subjective
ratings of injury severity at 2 years posttrauma were associated with errors of
addition (i.e., recalling the presence of acute symptoms 2 years posttrauma that
were not reported during the first assessment). Low levels of posttraumatic
stress severity and low subjective ratings of injury severity at 2 years
posttrauma were associated with errors of omission (i.e., omitting to recall
acute symptoms 2 years posttrauma that were reported during the first
assessment). These results suggest that retrospective reports of acute stress
symptoms should be interpreted cautiously because of the influence of current
symptoms on recall of acute symptoms.
PMID- 11009335
TI - Assessing problems with religious content: a comparison of rabbis and
psychologists.
AB - This study measured distinctions made by a sample of clergy and mental health
professionals in response to three categories of presenting problems with
religious content: mental disorder, religious or spiritual problem, and "pure"
religious problem. A national, random sample of rabbis (N = 111) and clinical
psychologists (N = 90) provided evaluations of three vignettes: schizophrenia,
mystical experience, and mourning. The participants evaluated the religious
etiology, helpfulness of psychiatric medication, and seriousness of the
presenting problems. The rabbis and psychologists distinguished between the three
diverse categories of presenting problems and concurred in their distinctions.
The results provide empirical evidence for the construct validity of the new DSM
IV category religious or spiritual problem (V62.89). Use of the V code allows for
more subtle distinctions among the variety of problems that persons bring to
clergy and mental health professionals. These distinctions may also provide a
foundation for the initiation of co-professional consultation.
PMID- 11009336
TI - Religion: a mediator of Anglo-American and Mexican attributional differences
toward symptoms of schizophrenia?
AB - This study examined the relationship of religiosity to attributions toward
schizophrenia, within a cultural context. Previous research suggests that on self
report measures, Mexicans endorse holding greater moral-religious values than do
their Anglo-American counterparts. Research also indicates that Mexicans,
relative to Anglo-Americans, tend to hold fewer blameworthy attributions and are
less likely to view patients with schizophrenia as responsible for the symptoms
of the disorder. In an analog study of 88 Mexican and 88 Anglo-American college
students asked to imagine that they have a brother with schizophrenia, this study
assessed two competing hypotheses regarding the role of religion in shaping
reactions to schizophrenia in a family member. For hypothesis 1, Baron and
Kenny's mediational model (1986) was used to assess whether moral religious
values may play a direct mediating role between ethnicity and controllability
attributions for schizophrenia. In other words, based on observations of previous
researchers, this set of analyses assessed whether ethnic differences in
controllability attributions might be explained by a religious or spiritual
tendency in Mexicans to view negative events, such as mental disability, as
rooted in divine factors beyond the patient's personal control. In contrast, a
second, competing, hypothesis was also assessed in this study: namely, that
greater religiosity would be positively correlated with increasing perceptions of
control over the symptoms of schizophrenia. This hypothesis stems from the
premise of several investigators that religious individuals may be more likely to
perceive another's adversity (such as having schizophrenia) as a punishment for
prior wrongdoings or for failure to try to help oneself. Results indicate support
for the latter hypothesis. Implications of the paradoxical finding, that Mexicans
were both more religious and more external in their attributions, are discussed.
PMID- 11009337
TI - Exhausted neurosurgeon describes a porcine brain implant to wine merchant with
Parkinson's disease
PMID- 11009338
TI - Trauma orientation and detection of violence histories in the psychiatric
emergency service.
PMID- 11009339
TI - Negative priming in schizophrenia: no evidence for reduced cognitive inhibition.
PMID- 11009340
TI - Heck arylation of endocyclic enecarbamates with diazonium salts. Improvements and
a concise enantioselective synthesis of (-)-codonopsinine.
AB - Total enantioselective synthesis of the natural (-)-codonopsinine was
accomplished in seven steps with an overall yield of approximately 16% starting
from the five-membered endocyclic enecarbamate 4. The total synthesis features a
highly efficient and stereoselective Heck arylation of endocyclic enecarbamate 4
with p-methoxybenzenediazonium tetrafluoroborate and a stereoselective
epoxidation/epoxide opening sequence as key steps.
PMID- 11009342
TI - PINDY: A novel, pinene-derived bipyridine ligand and its application in
asymmetric, Copper(I)-catalyzed allylic oxidation
AB - The title bipyridine ligand (+)-6(PINDY), prepared in five steps from (-)-beta
pinene, forms a stable complex with CuCl(2) (8) that has been characterized by X
ray crystallography to reveal an unusual geometry at Cu. Triflate 9 proved to
catalyze asymmetric allylic oxidation (10 --> 11; rt, approximately 30 min, 49
75% ee).
PMID- 11009341
TI - O-Glycosyl trichloroacetimidates bearing Fmoc as temporary hydroxy protecting
group: a new access to solid-phase oligosaccharide synthesis.
AB - Different O-glycosyl trichloroacetimidates bearing base sensitive Fmoc protected
hydroxy groups were efficiently prepared with CCl(3)CN using a catalytic amount
of sodium hydride. The resulting glycosyl donors were engaged in glycosylation
reactions both in solution and on solid support with a new ester-type linker with
good results. In both approaches, Fmoc groups were afterward quantitatively
cleaved using mild basic conditions.
PMID- 11009343
TI - A linear multiporphyrinic
AB - A linear multiporphyrinic [2]-rotaxane has been synthesized using the transition
metal-templating method for threading a gold(III)-incorporating macrocycle onto a
rodlike, phenanthroline-derived chelate bearing carboxylate end groups.
Stoppering has been performed by reacting the resulting prerotaxane with the
amino derivative of a zinc tetraarylporphyrin under EDC-HOBt activation. A 34%
yield has been realized for this one-pot, double amide bond formation.
PMID- 11009344
TI - Complete N-1 regiocontrol in the formation of N-arylimidazoles. Synthesis of the
active site His-Tyr side chain coupled dipeptide of cytochrome c oxidase.
AB - Under catalysis by copper(II) acetate, complete regiocontrol (N-1 versus N-3) was
obtained in the arylation of substituted imidazoles with aryllead(IV) reagents.
The mildness of the reaction conditions (rt, no added base) allows for the first
synthesis of the histidine-tyrosine side chain coupled dipeptide found in the
active site of cytochrome c oxidase.
PMID- 11009345
TI - A DFT and PM3 study of a hypothetical silicon-based sigma-allyl cation and sigma
allyl radical and higher homologues
AB - DFT and PM3 calculations were used to model the hypothetical sigma-allyl cation 1
Si(3)()(+) and sigma-allyl radical 1-Si(3)()(*). For both the cation and the
radical, the structure with equal Si-Si bond lengths and sigma-delocalized charge
or spin is predicted to be favored relative to a bond-localized "capped"
triquinane alternative. Higher homologues of 1-Si(3)()(+) and 1-Si(3)()(*) were
also modeled; they likewise are predicted to prefer sigma-delocalized structures.
PMID- 11009346
TI - Conformational analysis of alkylated biuret and triuret: evidence for helicity
and helical inversion in oligoisocyanates
AB - The conformations of several oligoisocyanates have been investigated by NMR in
order to study the onset and dynamics of helicity in polyisocyanates.
Pentaethylbiuret and hexaethyltriuret were found to adopt turns and helices in
solution. For hexaethyltriuret, symmetric and asymmetric helices are present. Not
only is an interconversion of these forms observed (DeltaG(SA)(double dagger) =
9.3 +/- 0.4 kcal/mol) but also a reversal of helicity (DeltaG(PM)(double dagger)
= 9.0 +/- 0.4 kcal/mol). The coalescence pattern for the latter process provides
direct evidence for a concerted, conrotatory helical inversion.
PMID- 11009348
TI - Fragmentation reaction via an ipso-attack in the multistep synthesis of
regioselectively functionalized Calix
AB - The acid-catalyzed convergent synthesis of a calix[8]arene containing a
regioselectively functionalized upper rim has been investigated through the
isolation and identification of cyclic and acyclic byproducts. Theoretical
calculations demonstrated that the synthetic process involves two types of
reaction mechanisms, one of which leads to the favorably constructed framework,
while the other causes undesirable fragmentation via ipso-substitution. A
possible rationale is proposed to explain the overall reaction pathways which
derive the calix[8]arene along with the byproducts.
PMID- 11009347
TI - Polymerized fluorescent liposomes incorporating lanthanide ions.
AB - This paper describes the design and synthesis of a polymerizable lipid capable of
complexing lanthanide ions. The lipid has been successfully incorporated into
liposomes and then polymerized. Fluorescence studies indicate that the
diacetylene (unpolymerized lipid) and the conjugated alkenes (after
polymerization) can be used as sensitizers for the lanthanide ion.
PMID- 11009349
TI - Solid-phase synthesis of 1,2,3, 4-tetrahydro-beta-carboline-containing
peptidomimetics.
AB - A solid-phase method for the synthesis of 1,2,3, 4-tetrahydro-beta-carboline
containing peptidomimetics has been developed. The key step in the strategy is
the Pictet-Spengler condensation of a resin-bound tryptophan-containing fragment
with an Fmoc-amino aldehyde.
PMID- 11009350
TI - Novel phenylazomethine dendrimers: synthesis and structural properties
AB - The novel dendrimers consisting of a pi-conjugated backbone, the dendritic
polyphenylazomethines (DPAs), were synthesized by the convergent method via the
dehydration of aromatic ketones with aromatic amines in the presence of
titanium(IV) tetrachloride. The obtained DPAs have a high solubility unlike the
conventional linear polyphenylazomethines. NMR studies revealed the
conformational rigidity of DPA G4. DPAs having many azomethine groups as the
coordination site for metal ions are expected to be novel ligands.
PMID- 11009351
TI - Diastereoselective intramolecular Ritter reaction: generation of a cis-fused
hexahydro-4aH-indeno[1,2-b]pyridine ring system with 4a,9b-diangular
substituents.
AB - Indanol intermediates 5, prepared via Michael addition of 1-indanone beta
ketoester and acrylonitrile followed by reduction or Grignard reaction of the
ketone group, were submitted to intramolecular Ritter reaction using various acid
reaction conditions to produce tricyclic lactams 4. This cis-fused hexahydro-4aH
indeno[1,2-b]pyridine ring system, substituted at both angular positions 4a and
9b, provides access to constrained analogues of non-peptide NK(1)-antagonists
with monocyclic piperidine structure.
PMID- 11009352
TI - Dipolar cycloaddition of novel 6-(nitrileoxidomethyl) penam sulfone: an efficient
route to a new class of beta-lactamase inhibitors.
AB - 6-(Nitrileoxidomethyl) penam sulfone intermediate was prepared in a few steps
starting from commercially available (+)-6-aminopenicillanic acid. This
intermediate underwent smooth 1, 3-dipolar cycloaddition reactions with various
alkenes and alkynes to give cycloadducts in moderate to good yields. By this new
method, several potent beta-lactamase inhibitors were synthesized. The regio- and
stereoselectivity outcomes of the cycloaddition process are also discussed.
PMID- 11009353
TI - Facile, completely regioselective 1,4-hydrogenations of C(60)-diaryltetrazine
monoadducts
AB - Thermal Diels-Alder reactions between C(60) and electron-deficient 3, 6-diaryl
1,2,4,5-tetrazines yield monoadducts possessing a diaryldihydropyridazine
function nested atop the fullerene. The diaryldihydropyridazine functions direct
a completely regioselective 1,4-hydrogenation, resulting in a racemic mixture of
bifunctional bisadduct (+/-)-3.
PMID- 11009354
TI - 1-Aminocyclopropaneboronic acid: synthesis and incorporation into an inhibitor of
hepatitis C virus NS3 protease.
AB - The previously unreported alpha,alpha-disubstituted 1-aminoboronate esters have
potential utility in peptidomimetic design, particularly against serine protease
targets. A concise synthesis of 1-aminocyclopropaneboronate pinanediol ester is
reported, and a peptidyl derivative is shown to have modest affinity (K(i) = 1.6
microM) for hepatitis C NS3 protease.
PMID- 11009355
TI - Effect of competing alkali metal cations on neutral Host's anion binding ability
AB - Anion binding by neutral hosts in organic solvents can be inhibited by the
presence of alkali metal cations. The binding inhibition is due to salt ion
pairing which increases in the order Cs(+) < K(+) < Na(+). The binding inhibition
can be reversed by using heteroditopic hosts that simultaneously bind both the
metal cation and the anion. The largest cation-induced enhancements are observed
with the less basic anions.
PMID- 11009356
TI - Novel synthesis of hybrid calixphyrin macrocycles
AB - The reaction of benzaldehyde with excess pyrrole at room temperature in the
absence of solvent affords a mixture of meso-substituted polypyrranes species.
After separation by column chromatography, these may be used to prepare a range
of calix[4]phyrin macrocycles by condensation with acetone under conditions of
acid catalysis.
PMID- 11009357
TI - Regioselective synthesis of unsymmetrical 3, 5-dialkyl-1-arylpyrazoles
AB - 3-Alkoxylmethyl-5-alkylpyrazoles undergo regioselective N-arylation with 4
fluoronitrobenzene in the presence of base to yield the corresponding 1-(4-nitro
phenyl)pyrazoles. Further elaboration of these intermediates furnishes a
practical synthesis of unsymmetrical 3,5-dialkyl-1-arypyrazoles. A tentative
explanation of the observed regioselectivities is provided.
PMID- 11009358
TI - Polymer support assisted selective functionalization of azoles using a palladium
catalyzed coupling reaction
AB - Regioselective palladium-catalyzed monoarylation of azoles was achieved using
iodobenzoate immobilized on an insoluble polymer support. The positional
selectivity for the coupling reaction was dramatically influenced by the presence
of CuI. No diarylation was observed in either case. Unsymmetrical diarylation was
also obtained with the polymer support using sequential coupling reactions.
PMID- 11009359
TI - Convenient route to super-expanded calixpyrroles: synthesis of Calix
AB - meso-Alkylporphyrinogen-like cyclic oligomers containing furans and pyrroles have
been synthesized by "3 + 2" and "4 + 2" approaches. Condensation of
5,5,10,10,15,15-hexaethyl-21, 22-dioxatetrapyrromethane with 2,5-bis[(alpha
hydroxy-alpha, alpha-dimethyl)furan] resulted in the formation of cyclic hexamer
and cyclic dodcamer. Effects of catalysts, temperature, inorganic additives,
solvent, and reaction concentration were examined.
PMID- 11009361
TI - Radical-initiated, skeletal rearrangements of Bicyclo
AB - Treatment of bicyclic lactones derived from Diels-Alder reactions of 3
carbomethoxy-2-pyrone under radical conditions leads to a series of interesting
skeletal rearrangements. The stereochemical and optical integrity of the starting
material are maintained throughout the process.
PMID- 11009360
TI - An efficient chiral moderator prepared from inexpensive (+)-3-carene: synthesis
of the HIV-1 non-nucleoside reverse transcriptase inhibitor DPC 963.
AB - The beta-amino alcohol 4 beta-morpholinocaran-3 alpha-ol is prepared by addition
of morpholine to alpha-3,4-epoxycarane utilizing anhydrous magnesium bromide as
Lewis acid promoter. The enantiopure amino alcohol is uniquely effective as a
chiral moderator for the addition of lithium cyclopropylacetylide to an
unprotected N-acylketimine. This reaction provides an efficient route to the
second generation NNRTI drug candidate DPC 963.
PMID- 11009362
TI - Efficient asymmetric synthesis of radicicol dimethyl ether: a novel application
of ring-forming olefin metathesis.
AB - A concise, stereospecific synthesis of radicicol dimethyl ether is presented. The
strategy relies on a convergent three-stage assembly of the 14-membered lactone
which has, as a key transformation, a novel ring-forming metathesis reaction
utilizing a vinyl epoxide.
PMID- 11009363
TI - Cobalt-catalyzed alkyne-nitrile cyclotrimerization to form pyridines in aqueous
solution.
AB - A new, water-soluble cobalt(I) catalyst has been used in the aqueous,
chemospecific, cyclotrimerization of one nitrile with two alkynes for the
synthesis of highly functionalized pyridines. Several different functional groups
are well incorporated in this transformation, including unprotected alcohols,
ketones, and amines. Double isotopic crossover data, as well as nitrile
dependence on the rate of product formation, suggest associative rate-determining
coordination of the nitrile.
PMID- 11009364
TI - The mild cleavage of 2-amino-2-deoxy-D-glucoside methoxycarbonyl derivatives.
AB - The conversion of methyl carbamate to the corresponding free amine is described
for a series of 2-amino-2-deoxy-D-glucosamine derivatives. Cleavage of
methoxycarbonyl moiety with MeSiCl(3) and triethylamine in dry THF at 60 degrees
C and subsequent aqueous hydrolysis yields the free amine in 54 to 93% yields.
The selective cleavage of methyl carbamates with MeSiCl(3) in the presence of a
2,2,2-trichloroethoxycarbonyl group or 2-azido glycosides affords selectively,
orthogonal N-deprotected carbohydrates.
PMID- 11009365
TI - Efficient synthesis of the D-ring fragment of cobyric acid
AB - The synthesis of a highly functionalized 4,5-dihydro-3H-pyrrol, namely, the D
ring fragment 5a of cobyric acid (1), is described in this letter. A very
efficient assembly to 5a involves CBS-reduction of 10, a [2,3] Wittig-Still
rearrangement, and a stereoselective Michael addition to a nitro olefin.
PMID- 11009367
TI - Stereocontrol in rare earth metal triflate-catalyzed 1,3-dipolar cycloaddition
reaction of 2-benzopyrylium-4-olate with aldehydes
AB - Exo-cycloadduct was obtained with high stereoselectivity by the addition of
ytterbium triflate (Yb(OTf)(3)) (10 mol %) in the rhodium(II) acetate
(Rh(2)(OAc)(4))-catalyzed decomposition of o-(methoxycarbonyl)-alpha
diazoacetophenone in the presence of benzaldehyde. In the reaction in the absence
of Yb(OTf)(3), almost no selectivity was obtained. Stereoselectivity in the
reactions with p-nitrobenzaldehyde, p-anisaldehyde, and benzyloxyacetaldehyde
could be also controlled to high exo preference by the addition of Yb(OTf)(3).
PMID- 11009366
TI - Reaction of COTC with glutathione: structure of the putative glyoxalase I
inhibitor.
AB - The structure of the active glyoxalase I inhibitor derived from the Streptomyces
griseosporeus metabolite COTC 1 has been conclusively identified by means of
total synthesis as 2c. Human glyoxalase I is competitively inhibited by 2c
(K(i)() = 183 +/- 6 microM) but is not inhibited by 1 itself.
PMID- 11009368
TI - A novel strategy for designing irreversible inhibitors of metalloproteases:
acetals as latent electrophiles that interact with catalytic nucleophile at the
active site.
AB - A new strategy for design of irreversible inactivators for carboxypeptidase A
(CPA), a prototypic zinc protease, has been developed by exploiting the property
of acetals to generate an oxacarbenium ion intermediate in the conversion into
the corresponding carbonyl compounds. The design strategy is exemplified by 2
benzyl-5-alkyl-3,5-dioxapentanoic acids (1a-c). Interestingly, (R)-1b is slightly
more potent than an (S)-1b as an inactivator of CPA.
PMID- 11009369
TI - In situ preparation of a highly active N-heterocyclic carbene-coordinated olefin
metathesis catalyst.
AB - Highly active N-heterocyclic carbene-coordinated catalysts may be synthesized and
used in situ, without requiring prior isolation of the catalyst. Activation of
this in situ catalyst with ethereal HCl dramatically reduces the reaction times
required for high conversions. A variety of alpha,beta-unsaturated carbonyl
containing substrates participate readily in cross and ring-closing metathesis
reactions using this preparation.
PMID- 11009370
TI - Highly enantioselective addition of diethylzinc to diphenylphosphinoyl imines
under dual amino Alcohol/Halosilane mediation
AB - Arylethylene-derived, enantiomerically pure amino alcohols have been evaluated as
ligands for the dual-catalyzed (amino alcohol/halosilane) enantioselective
addition of diethylzinc to diphenylphosphinoyl imines. Among them, the
conformationally restricted 9-fluorenone-derived ligand 4c provides the highest
enantioselectivities so far reported over a range of substrate imines.
PMID- 11009371
TI - A synthetic transmembrane polyether model active in lipid bilayers.
AB - A model polyether-based ion channel-like compound was rationally designed and
synthesized. Macromolecules 1c-f were incorporated into phospholipid vesicles and
shown to facilitate the transmembrane sodium transport.
PMID- 11009373
TI - Chiral discrimination in hydrogen-bonded
AB - A series of racemic [7]helicenes have been prepared and characterized both in
solution and in the solid state. Despite the helicenes having the ability to self
assemble in a variety of stereochemical and topological relationships, they
formed only enantiomerically pure dimers held together by two pairs of
cooperative hydrogen bonds. The self-assembly process was enantiospecific in
solution and diastereoselective in the crystal.
PMID- 11009372
TI - First asymmetric hetero Diels-Alder reaction of 1-sulfinyl dienes with nitroso
derivatives. A new entry to the synthesis of optically pure 1,4-imino-L-ribitol
derivatives.
AB - Hetero Diels-Alder (HDA) cycloaddition of chiral 1-p-tolylsulfinyl-1,3-pentadiene
with benzyl nitrosoformate, under mild conditions, yields 2H-1,2-oxazine 3 with
complete regioselectivity and pi-facial diastereoselectivity. Sequential
osmylation and protection of the resulting glycol gives the oxazine 5 which is
directly transformed into enantiomerically pure 1,4,5-trideoxy-1,4-imino-L
ribitol 8 by reduction under Pd/C.
PMID- 11009374
TI - A facile stereocontrolled synthesis of anti-alpha-(trifluoromethyl)-beta-amino
alcohols.
AB - A short stereocontrolled preparation of anti-alpha-(trifluoromethyl)-beta-amino
alcohols is described, involving an initial CF(3) transfer to cinnamaldehyde and
a one-step, three-component condensation of 3,3,3-trifluorolactic aldehyde, an
alkenyl (aryl) boronic acid, and an amine. Applying this methodology to chiral
3,3,3-trifluorolactic aldehyde allowed us to generate an amino alcohol
enantioselectively in 92% ee.
PMID- 11009375
TI - Novel total synthesis of the anticancer natural product dysidiolide.
AB - The marine natural product dysidiolide has been synthesized in a highly
diastereoselective fashion that features the sequential transfer of chirality
from a cyclohexenone precursor.
PMID- 11009376
TI - A concise route to (-)-kainic acid.
AB - A concise route to (-)-kainic acid from enantiopure (+)-cis-4-carbobenzoxyamino-2
cyclopentenol has been devised by employing concurrent Chugaev syn-elimination
and intramolecular ene reaction as the key step.
PMID- 11009377
TI - A facile synthesis of dragmacidin B and 2,5-bis(6'-bromo-3'-indolyl)piperazine.
AB - A short synthesis of dragmacidin B (1), 2,5-bis(6'-bromo-3'-indolyl)piperazine
(2), and corresponding didebromo analogues 8 and 9 is described. The key steps
involve the dimerization of oxotryptamines 4 and 11 to give bis(indolyl)pyrazines
5 and 12, which upon selective reduction and reductive methylation with sodium
cyanoborohydride afforded the requisite piperazine natural products.
PMID- 11009378
TI - Synthesis of novel acetylenic cyclophanes with helical chirality: potential new
structures for liquid crystals
AB - The synthesis of a series of novel acetylenic cyclophanes is described. X-ray
crystallographic analysis of the core structure revealed a twisted conformation
with helical chirality. Preliminary results suggest that these cyclophanes, with
appropriate functionality, have the potential to act as unique liquid crystalline
materials.
PMID- 11009379
TI - A diastereocontrolled synthesis of (+)-febrifugine: a potent antimalarial
piperidine alkaloid.
AB - A diastereocontrolled synthesis of (+)-febrifugine, a potent antimalarial
piperidine alkaloid, has been achieved using a chiral block having a
bicyclo[3.2.1]octane framework which exhibits inherent convex-face selectivity.
PMID- 11009380
TI - Yb(OTf)(3)-Catalyzed oxymercuration of homoallylic alcohol-derived hemiacetals
and hemiketals.
AB - 1,3-Diol synthons, protected as acetonides or benzylidene acetals, may be
synthesized efficiently from homoallylic alcohols and acetone or benzaldehyde by
oxymercuration of the derived hemiketals and hemiacetals with HgClOAc. The use of
catalytic amounts of Yb(OTf)(3) is crucial to the success of the reaction, which
was determined to be reversible.
PMID- 11009381
TI - Convenient iterative synthesis of an octameric tetracarboxylate-functionalized
oligophenylene rod with divergent end groups
AB - Oligo(p-phenylene) rigid rod 10 is synthesized via a functional group-tolerant
molecular doubling approach. Preparative chromatographic methods, protecting
groups, boronic acid isolations, and Grignard or organolithium reagents are not
used. The convenient synthesis of well-defined, polar-functionalized
oligophenylene rigid rods could afford ready access to a variety of useful
electronic organic materials.
PMID- 11009383
TI - An expeditious route to eight- and nine-membered carbocycles based on a RCM-ring
fragmentation strategy
AB - The presence of a temporary one-atom internal tether in 1,9-deca- and 1,10
undecadienes allows their efficient ring-closing metathesis (RCM). Cleavage of
the bridging tether of the resulting bicycles provides eight- or nine-membered
carbocycles, medium-sized rings that are difficult to assemble using other
currently available procedures.
PMID- 11009382
TI - Rhodium-catalyzed formylation of organomercurials: application to efficient
polyol synthesis.
AB - The rhodium-catalyzed formylation of organomercurials-a new transformation of
organomercurials-is reported. The addition of 0.50 equiv of 1,4
diazabicyclo[2.2.2]octane (DABCO) was found to promote the reaction, and it is
postulated that the DABCO acts as a ligand for mercury. Several examples are
presented to document the scope of the reaction. This reaction was developed in
the context of a larger program focused on the development of efficient
strategies for the synthesis of polyol-derived natural products, and an efficient
(8 steps) synthesis of Tolypothrix pentaether that employs this methodology is
reported.
PMID- 11009384
TI - Phosphorus pentasulfide: A mild and versatile Catalyst/Reagent for the
preparation of dithiocarboxylic esters
AB - The reaction of carboxylic acids (1) with a variety of thiols or alcohols in the
presence of phosphorus pentasulfide (P(4)S(10)) as a catalyst and reagent (20-40
mol %) proceeded effectively to afford the corresponding dithiocarboxylic esters
(2) in high yields.
PMID- 11009385
TI - Construction of 4-hydroxy-2-pyridinones. Total synthesis of (+)-sambutoxin.
AB - Total synthesis of (+)-sambutoxin has been achieved, establishing the relative
and absolute stereochemistry of the naturally occurring mycotoxin. Efforts
feature methodology for enantiocontrolled construction of 1,3-anti-dimethyl
arrays and a novel Saegusa oxidation to provide a pyridinone methide leading to
formation of the central dihydropyran ring.
PMID- 11009386
TI - Mild and general cross-coupling of (alpha-Alkoxyvinyl)silanols and -silyl
hydrides
AB - (alpha-Alkoxyvinyl)silanols and (alpha-alkoxyvinyl)silyl hydrides are efficiently
converted to aryl vinyl ethers by a palladium(0)-catalyzed cross-coupling
reaction with aryl halides in the presence of tetrabutylammonium fluoride or
hydroxide. Yields are generally high, and the reaction is compatible with a wide
range of functional groups.
PMID- 11009387
TI - Triple hydroxylation of tetracenomycin A2 to tetracenomycin C involving two
molecules of O(2) and one molecule of H(2)O.
AB - The TcmG or ElmG oxygenase-catalyzed triple hydroxylation of tetracenomycin (Tcm)
A2 to Tcm C proceeds via a novel monooxygenase-dioxygenase mechanism, deriving
the 4- and 12a-OH groups of Tcm C from two molecules of O(2) and the 4a-OH group
of Tcm C from a molecule of H(2)O. These results suggest a mechanistic analogy
among TcmG, ElmG, and the bacterial and fungal hydroquinone epoxidizing
dioxygenases, as well as the mammalian vitamin K-dependent gamma-glutamyl
carboxylase.
PMID- 11009388
TI - Thiol ester-boronic acid cross-coupling. Catalysis using alkylative activation of
the palladium thiolate intermediate.
AB - Thiol esters and boronic acids do not participate in cross-coupling in the
presence of palladium catalysts. However, efficient palladium-catalyzed thiol
ester-boronic acid cross-coupling is observed when simple alkylating agents are
present. Alkylative conversion of the very stable palladium-thiolate bond to a
labile palladium-thioether bond is presumed to be crucial to the catalysis. Of
the systems studied, 4-halo-n-butyl thiol esters were most effective in this
cross-coupling.
PMID- 11009389
TI - Formal synthesis of (+/-)-dendrobine: use of the amidofuran
cycloaddition/rearrangement sequence.
AB - The formal synthesis of the alkaloid (+/-)-dendrobine (4) was accomplished using
the IMDAF cycloaddition/rearrangement sequence of a furanyl carbamate. Conversion
of the rearranged cycloadduct to Kende's advanced intermediate in eight steps
completed the formal synthesis of (+/-)-dendrobine.
PMID- 11009390
TI - A general synthetic method for the formation of substituted 5-aminotetrazoles
from thioureas: a strategy for diversity amplification.
AB - A general method for the synthesis of 5-aminotetrazoles is outlined using the
mercury(II)-promoted attack of azide anion on a thiourea. The reaction proceeds
through a guanyl azide intermediate, which undergoes electrocyclization to the
tetrazole. The method is high yielding and provides access to mono-, di-, and
trisubstituted 5-aminotetrazoles, targets of potential interest for combinatorial
library development.
PMID- 11009391
TI - Investigation of a dialkylation approach for enantioselective construction of
vicinal quaternary stereocenters.
AB - A detailed study of the dialkylation of dianions derived from dihydroisoindigo 1
with enantiopure ditriflate 2 is reported. The LHMDS-mediated process has been
optimized to give C(2)-symmetric product 3 with high selectivity (C(2)
selectivity 3:5 = 100:1; C(2):C(1) selectivity = 8:1). Stereoselection in the
C(2) manifold is determined in both the bimolecular and intramolecular alkylation
steps.
PMID- 11009392
TI - Synthesis of carbapenam skeletons using a ruthenium-catalyzed cyclization.
AB - Carbapenam is a very important skeleton of beta-lactam antibiotics, and it has a
highly strained structure. When enynes 9 were treated with RuH(2)CO(PPh(3))(3)
(10 mol %) in toluene upon heating, carbapenams 10 were obtained in good yields.
PMID- 11009393
TI - The principle of laplace and scaling of ventricular wall stress and blood
pressure in mammals and birds.
AB - Maximum left ventricular wall stress is calculated at end-diastolic volume and
systemic arterial diastolic blood pressure, according to a thick-walled model for
the principle of Laplace. Stress is independent of body mass and averages 13.9
kPa (+/-2.3; 95% confidence interval) in 24 species of mammals weighing 0.025
4,000 kg and 15.5 kPa (+/-4.7) in 12 birds weighing 0.014-110 kg. Birds have
higher arterial blood pressures and larger hearts than mammals. Systolic and
diastolic arterial blood pressures increase with body mass according to M(0.05)
in mammals, and heart mass increases according to M(1.06) in the same species,
further supporting the principle. However, blood pressure in birds is independent
of body mass, and heart mass scales isometrically. End-diastolic stress values,
calculated according to Laplace, are about one-third of peak stresses recorded in
isolated mammalian myocardial preparations.
PMID- 11009394
TI - Cold tolerance and the regulation of cardiac performance and hemolymph
distribution in Maja squinado (Crustacea: decapoda).
AB - Elevated Mg(2+) levels in the hemolymph ([Mg(2+)](HL)) of brachyuran crabs have
recently been demonstrated to limit cold tolerance by reducing motor and
circulatory activity. Therefore, the limiting function of elevated [Mg(2+)](HL)
on circulatory performance and arterial hemolymph flow was investigated by the
pulsed-Doppler technique in the spider crab Maja squinado during progressive
cooling from 12 degrees to 0 degrees C. [Mg(2+)](HL) were reduced from control
levels of 39.9 mmol L(-1) to levels of 6.1 mmol L(-1) by incubation in magnesium
reduced seawater. At 12 degrees C cardiac output was 13.9+/-2.4 mL kg(-1) min(-1)
and stroke volume 0.2+/-0.04 mL kg(-1) min(-1) in control animals. In
[Mg(2+)](HL)-reduced animals cardiac output increased to 43.6+/-5.0 mL kg(-1)
min(-1) and stroke volume rose to 0.6+/-0.1 mL kg(-1) min(-1). Temperature
reduction in control animals revealed a break point at 8 degrees C linked to a
major redirection of hemolymph flow from lateral to sternal and hepatic arteries.
Cardiac output and heart rate dropped sharply during cooling until transiently
constant values were reached. Further heart rate reduction occurred below 4.5
degrees C. Such a plateau was not detected in [Mg(2+)](HL)-reduced animals where
the break point decreased to 6 degrees C, also indicated by a sharp drop in heart
rate and cardiac output and the redirection of hemolymph flow. It is concluded
that progressive cooling brings the animals from a temperature range of optimum
cardiac performance into a deleterious range when aerobic scope for activity
falls before critical temperatures are reached. Reduction of [Mg(2+)](HL) shifts
this transition to lower temperatures. These findings support a limiting role for
[Mg(2+)](HL) in thermal tolerance.
PMID- 11009395
TI - Effects of food shortage and oversupply on energy utilization, histology, and
function of the gut in nestling song thrushes (Turdus philomelos).
AB - We measured food intake, digestive efficiency, body mass increments, resting
metabolic rate (RMR), carcass fat content, size and histological structure of the
gut, and the rate of intestinal brush border uptake of l-proline in song thrush
(Turdus philomelos) nestlings subjected to food shortage or food surplus under
laboratory conditions. We assigned nestlings between 3 and 7 d of age to one of
the following treatments: (1) food restriction, which resulted in a slowed growth
at the rate found in undernourished, wild nestlings; (2) overfeeding, which
totally suppressed begging; and (3) intermediate feeding. Threefold differences
in energy consumption caused fivefold differences in body mass increments of the
nestlings. Despite this, body mass-corrected RMR and intestinal mass were not
affected by the feeding regime. The energy content of fecal output was highest in
food-restricted birds, while their carcass fat content was lowest among treatment
groups. Intestinal uptake rates of l-proline were low in the overfed and
intermediate-fed young but significantly increased in the food-restricted birds,
who attempted to maximize their rates of growth and development within the
restrictive limits set by feeding regime. We noted a marked decrease of
intestinal villi height in overfed birds as compared to intermediate-fed and food
restricted nestlings. We conclude that song thrush nestlings are characterized by
a limited plasticity of their developmental program, which prohibits overfed
nestlings from significantly up-regulating their gut function to accommodate
increased food intake. This suggests that they already grew at a rate close to
their physiological maximum. We suggest two interpretations: (1) under natural
conditions, song thrush nestlings do not face frequent, unpredictable
fluctuations in food abundance that could select for developmental plasticity, or
(2) strong selection for uniform adult phenotypes prevents flexible developmental
trajectories, which would result in a diversity of adult phenotypes.
PMID- 11009396
TI - Comparative and behavioral analyses of preferred speed: Anolis lizards as a model
system.
AB - I quantified the movement patterns of eight morphologically and ecologically
diverse Caribbean Anolis lizard species in the field to address the following
questions: (1) Do these eight species move at preferred speeds, and if so, what
are these speeds? (2) What proportion of their maximum sprinting capacities do
the anole species use when moving undisturbed? (3) What percentage of the time do
lizards spend moving, and how far do they typically travel on a daily basis? (4)
Have the preferred speeds of anoles coevolved with structural habitat use? Most
of the distributions of speeds were highly skewed, with a preponderance of slow
speed locomotion (<20% of maximum capacity). Median speeds varied almost
eightfold among species, from a low of 4.9 cm/s (3.0% of maximum) to a high of
38.0 cm/s (22.4% of maximum). For all eight species, at least 75% of their
locomotor movements took place between 0% and 40% of maximum capacity. The eight
species varied almost 15-fold in the percentage of time they spent moving,
indicating that not all anole species are equally sedentary. Through usage of
modern comparative methods, I showed that Anolis species that move slowly through
their environments also tend to use narrow perch diameters and have large habitat
breadths. These findings show how evolutionary approaches can be profitably
integrated with physiological data to understand how species use their habitats.
PMID- 11009397
TI - Impact of externally attached loggers on the diving behaviour of the king
penguin.
AB - The impact of relatively small externally attached time series recorders on some
foraging parameters of seabirds was investigated during the austral summer of
1995 by monitoring the diving behaviour of 10 free-ranging king penguins
(Aptenodytes patagonicus) over one foraging trip. Time-depth recorders were
implanted in the abdominal cavities of the birds, and half of the animals also
had dummy loggers attached on their backs. Although most of the diving behaviour
was not significantly affected by the external loggers (P>0.05), the birds with
externally attached loggers performed almost twice as many shallow dives, between
0 and 10 m depth, as the birds without external loggers. These shallow dives
interrupted more frequently the deep-diving sequences in the case of birds with
external loggers (percentage of deep dives followed by deep dives: 46% for birds
with implants only vs. 26% for birds with an external attachment). Finally, the
distribution pattern of the postdive durations plotted against the hour of the
day was more heterogeneous for the birds with an external package. In addition,
these penguins had extended surfacing times between two deep dives compared to
birds without external attachments (P<0.0001). These results suggest the
existence of an extra energy cost induced by externally attached loggers.
PMID- 11009398
TI - Time-course changes in the expression of Na+, K+-ATPase in gills and pyloric
caeca of brown trout (Salmo trutta) during acclimation to seawater.
AB - Changes in protein and mRNA expression of Na(+),K(+)-ATPase in gills and pyloric
caeca of brown trout were investigated on a detailed time course after transfer
from freshwater to 25 ppt seawater (SW). A transient deflection in plasma
osmolality and muscle water content lasting from 4 h until day 3 was followed by
restoration of hydromineral balance from day 5 onward. Gills and pyloric caeca
responded to SW transfer by increasing Na(+),K(+)-ATPase activity from days 5 and
3, respectively, onward. In both tissues, this response was preceded by an
increase in alpha-subunit Na(+), K(+)-ATPase mRNA as early as 12 h posttransfer.
The similarity of the response in these two organs suggests that they both play
significant physiological roles in restoring hydromineral balance after abrupt
increase in salinity. Further, SW transfer induced a slight, though significant,
increase in primary gill filament Na(+), K(+)-ATPase immunoreactive (NKIR) cell
abundance. This was paralleled by a marked (50%) decrease in secondary lamellar
NKIR cell abundance after less than 1 d in SW. Thus, SW acclimation in brown
trout is characterised by a lasting decrease in overall NKIR cell abundance in
the gill. We propose that SW transfer stimulates Na(+),K(+)-ATPase enzymatic
activity within individual chloride cells long before (<1 d) it becomes apparent
in measurements of whole-gill homogenate enzymatic activity. This is supported by
the early stabilisation (12 h) of hydromineral balance.
PMID- 11009399
TI - Intestinal nutrient uptake measurements and tissue damage: validating the everted
sleeves method.
AB - The reliability of methods for nutrient uptake measurements across the intestinal
epithelium relies on the integrity of the mucosal epithelium and the enterocytes.
We tested effects of tissue handling during the "everted sleeves method" on the
length of intestinal villi, the surface magnification, the circumference of the
gut, and the thickness of the muscle layer in sunbirds (Nectarinia osea), chicken
(Gallus gallus), and mice (Mus domesticus). The sunbird has thin and delicate
intestinal villi that are greatly affected by the everted sleeves method. After
eversion and incubation, villi lost 30% of their original length. The severe
tissue damage coincides with uptake measurements for glucose that were an order
of magnitude lower than in other nectar-feeding (nectarivorous) birds of similar
body size. Tissue handling during the everted sleeves method had significant
effects on morphometric parameters of chicken and mouse intestines, but on a
light-microscopical level, the tissue integrity and the cytology of the
enterocytes were not altered. Therefore, we think that the everted sleeves method
renders reliable and reproducible measurements of nutrient uptake in those
species. We conclude that a histological evaluation is necessary to assess the
reliability of the method before it is applied to adults or to the developmental
stage of any species.
PMID- 11009400
TI - The adjustment of avian metabolic rates and water fluxes to desert environments.
AB - We tested the hypothesis that birds in arid environments, where primary
productivity is low and surface water is scarce, have reduced energy expenditure
and water loss compared with their mesic counterparts. Using both conventional
least squares regression and regression based on phylogenetically independent
contrasts, we showed that birds from desert habitats have reduced basal and field
metabolic rates compared with species from mesic areas. Previous work showed that
desert birds have reduced rates of total evaporative water loss when exposed to
moderate environmental temperatures in the laboratory. We tested whether reduced
rates of total evaporative water loss translate into low field water fluxes.
Conventional ANCOVA indicated that desert birds have reduced water fluxes, but an
analysis based on phylogenetically independent contrasts did not support this
finding, despite the wide array of taxonomic affiliations of species in the data
set. We conclude that the high ambient temperatures, the low primary
productivity, and the water scarcity in desert environments have selected for or
resulted in reduced rates of energy expenditure and evaporative water loss in
birds that live in these climes.
PMID- 11009401
TI - Xantusiid lizards have low energy, water, and food requirements.
AB - Lizards in the family Xantusiidae (the night lizards) are known to have resting
metabolic rates that are only half those of other lizards of comparable size. We
evaluated whether xantusiids also have low field metabolic rates (FMR) and food
requirements by measuring FMR and water flux rates with doubly labeled water in
three xantusiid species in their natural habitats. Free-living Xantusia vigilis,
Xantusia henshawi, and Xantusia riversiana processed energy and water very
slowly, about one-third as fast as do other reptiles of similar size. Xantusiid
lizards have a distinctive life history that is characterized by very slow growth
and low reproductive rates, and they are intensely reclusive. This general
lifestyle is also found in some species that live in environments with scarce
food resources, such as in caves and in arid habitats, and these species may also
have relatively low energy requirements.
PMID- 11009402
TI - The effect of changing the gaseous diffusion coefficient on the mass loss pattern
of Hyalophora cecropia pupae.
AB - The importance of gas phase diffusion in insect gas exchange remains unclear. The
role of diffusion in gas exchange of developing Hyalophora cecropia pupae was
examined by altering the gaseous diffusion coefficient in the breathing mixture.
Gaseous diffusion coefficients were manipulated by substituting helium or sulfur
hexafluoride for the nitrogen usually present in air. Sensitive mass loss
recordings were employed to monitor gas exchange activity. Mass loss recordings
showed a two-phase cycle, open and closed-flutter. Mass loss rates during the
open and closed-flutter periods were not altered in proportion to the changes
induced in the rate of diffusion. Open-phase duration was inversely and
proportionally related to the diffusion coefficient. These results are consistent
with changes in spiracle resistance or convective flow during the open period in
response to a change in the diffusion coefficient. In addition, they indicate a
significant gas phase diffusive resistance within the pupal tracheal system. This
previously unreported gas phase resistance appears to be a major determinant of
the duration of the open period and thus of overall water loss rates in these
pupae.
PMID- 11009403
TI - Similarity of vasorelaxant effects of natriuretic peptides in isolated blood
vessels of salmonids.
AB - Natriuretic peptides (NPs) have been implicated in cardiovascular regulation in
rainbow trout (Oncorhyncus mykiss), and it has been observed that the
vasorelaxant activity of distinct trout and human NPs is similar in isolated
trout arteries. This study characterizes the response of a variety of vessels
from rainbow trout and other salmonids to different NPs. The effects of
heterologous (rat atrial and human atrial) and homologous (rainbow trout atrial
and rainbow trout ventricular) NPs were examined in precontracted efferent
branchial arteries from rainbow trout (O. mykiss, Kamloops strain), lake
whitefish (Coregonus clupeaformis), and in rainbow trout celiacomesenteric
arteries and anterior cardinal veins. The response to mammalian NPs was also
examined in efferent branchial arteries from the steelhead (O. mykiss, Skamania
strain), coho salmon (Oncorhyncus kisutch), brook trout (Salvelinus fontinalis),
and brown trout (Salmo trutta). In general, there were relatively few differences
that were species, peptide, or vessel specific. There was no difference in the
sensitivity (concentration producing a half-maximal response EC(50)) or efficacy
(percent relaxation, i.e., E(max)) of trout or whitefish efferent branchial
arteries to any NP, except human NP, which was significantly less effective
(greater EC(50) and lower E(max)) in whitefish arteries. There were no
differences in E(max) of mammalian NPs in efferent branchial arteries from any
species, and only coho and brook trout had significantly different EC(50)'s
(coho, 1.0+/-0.2 nM; brook trout, 4. 2+/-0.6 nM; and other species, from 1.9 to
3.5 nM). Rainbow and coho anterior cardinal veins were less sensitive than
arteries to mammalian NPs (EC(50)'s; 8.8+/-2.0, 2.0+/-0.1 vs. 3.0+/-0.9, 1.0+/-0.
2, respectively), whereas brown trout veins were more sensitive (1. 0+/-0.2,
3.5+/-1.3, respectively). Sodium nitroprusside (SNP), which activates soluble
guanylate cyclase, was vasodilatory, albeit significantly less potent than all
NPs, in efferent branchial arteries of all species. SNP was significantly more
potent in trout than whitefish efferent branchial arteries, whereas it was
equally efficacious in these vessels. These results demonstrate that multiple
vessels from various salmonids are similarly responsive to the vasorelaxant
effects of a variety of NPs and that the salmonid NP receptor has relatively
little ability to discriminate between homologous and heterologous peptides. We
conclude that the vascular NP receptor complex is highly conserved among
salmonids. Further, salmonids utilize cyclic guanosine monophosphate (cGMP)
elevations for reductions of vascular tonus by both particulate and soluble
guanylate cyclase pathways.
PMID- 11009404
TI - Influence of environmental oxygen on development and hatching of aquatic eggs of
the australian frog, Crinia georgiana.
AB - The effect of oxygen partial pressure (Po(2)) on development and hatching was
investigated in aquatic embryos of the myobatrachid frog, Crinia georgiana, in
the field and in the laboratory. Eggs from 29 field nests experienced widely
variable Po(2) but similar temperatures. Mean Po(2) in different nests ranged
between 2.9 and 19.3 kPa (grand mean 12.9 kPa), and mean temperature ranged
between 11.9 degrees and 16.8 degrees C (grand mean 13.7 degrees C). There was no
detectable effect of Po(2) or temperature on development rate or hatching time in
the field, except in one nest at 2.9 kPa where the embryos died, presumably in
association with hypoxia. Laboratory eggs were incubated at 15 degrees C at a
range of Po(2) between 2 and 25 kPa. Between 5 and 25 kPa, there was almost no
effect of Po(2) on development rate to stage 26, but the embryos hatched
progressively earlier-at earlier stages and lower gut-free body mass-at lower
Po(2). At 2 kPa, development was severely delayed, growth of the embryo slowed,
and morphological anomalies appeared. A high tolerance to low Po(2) may be an
adaptation to embryonic development in the potentially hypoxic, aquatic
environment.
PMID- 11009405
TI - Conflicts between courtship and thermoregulation: the thermal ecology of amorous
male garter snakes (Thamnophis sirtalis parietalis, colubridae).
AB - Thermoregulatory behavior is an important component of daily activities for many
reptiles, especially for small heliothermic (sun-basking) species that inhabit
cold climates. However, the relative costs and benefits of thermoregulation
depend on numerous factors, such that reptiles may sometimes accord a low
priority to precise control of body temperatures. We observed and radio tracked
garter snakes (Thamnophis sirtalis parietalis) in central Manitoba during the
mating season (spring). Previous studies on this species have documented precise
behavioral regulation of body temperatures during summer. In contrast, the
courting snakes that we studied in springtime spent little time in overt
thermoregulatory behavior. Body temperatures were extremely variable (both in
outdoor enclosures and in the field) despite abundant opportunities for more
precise thermal control. These small elongate reptiles cool so quickly (relative
to the time periods needed for effective courtship) that any benefit to higher
body temperatures would be transitory at best. Experiments show that hotter males
are no better at obtaining matings or at detecting predators. Thus, male garter
snakes concentrate on courtship rather than on basking. In the face of
conflicting priorities, reptiles may often forgo precise thermoregulation because
its benefits are too low, and its costs too high, compared with alternative
behaviors.
PMID- 11009406
TI - The energy budget of captive Siberian hamsters, Phodopus sungorus, exposed to
photoperiod changes: mass loss is caused by a voluntary decrease in food intake.
AB - Unlike most nonhibernating small mammals, Siberian hamsters (Phodopus sungorus)
undergo a pronounced mass loss, almost exclusively as white adipose tissues, in
response to a switch from long- to short-photoperiod exposure. This mass loss can
be caused by an increase in the rate of energy expenditure, a decrease in the
rate of energy intake, or a decrease in assimilation efficiency. In order to
determine how they relate to photoperiod-induced mass loss, we measured these
energy budget components every 2 wk on 12 captive Siberian hamsters exposed to 8
wk of long photoperiod followed by 12 wk of short photoperiod. Body mass
decreased shortly after short-photoperiod exposure. This was accompanied by an
immediate decrease in the rate of energy intake and, after a 2-wk delay, by a
decrease in the rate of energy expenditure. The overall cumulative decrease in
energy intake (376 kJ) could account for the mass loss (249 kJ) observed during
short-photoperiod exposure. Regression analyses indicated that only the rate of
energy intake was significantly related to the rate of mass change. Therefore, we
conclude that photoperiod-induced mass loss in Siberian hamsters is caused by a
decrease in the rate of food intake, rather than by changes in energy expenditure
or in assimilation efficiency.
PMID- 11009407
TI - Mechanism of delayed ovulation in a vespertilionid bat, scotophilus heathi: role
of gonadotropin, insulin, and insulin-like growth factor-1.
AB - The aim of this study was to evaluate the effects of luteinizing hormone (LH),
follicle-stimulating hormone (FSH), insulin, and insulin-like growth factor-1
(IGF-1) on ovarian androstenedione synthesis to understand the mechanism
responsible for delayed ovulation in Scotophilus heathi. We found that LH
stimulated a dose-dependent increase in androstenedione synthesis by the ovary in
vitro. This study also showed a clear seasonal variation in the ability of the
ovary to produce androstenedione in vitro in response to LH and FSH stimulation.
In response to LH and FSH, maximum quantities of androstenedione were produced
during recrudescence in November. The same doses of gonadotropins during the
preovulatory period in February stimulated comparatively low androstenedione
secretion by the ovary. On the basis of these data, we suggest that in S. heathi,
ovarian responsiveness to LH and FSH peaks during recrudescence. This study also
showed a seasonal variation in the effects of insulin and IGF-1 on ovarian
androstenedione production in vitro. Peak ovarian responsiveness to insulin and
IGF-1 was observed during quiescence in September. It is hypothesized that
increased insulin/IGF-1 sensitivity during September may be responsible for
increased responsiveness to LH. Increased LH release, if coincident with the
period of enhanced ovarian responsiveness to LH, may result in the excessive
androstenedione production responsible for delayed ovulation in S. heathi.
PMID- 11009408
TI - The quiet revolution: biodiversity informatics and the internet.
AB - The massive development of biodiversity-related information systems on the
Internet has created much that appears exciting but chaotic, a diversity to match
biodiversity itself. This richness and the arrays of new sources are
counterbalanced by the maddening difficulty in knowing what is where, or of
comparing like with like. But quietly, behind the first waves of exuberance,
biologists and computer scientists have started to pull together in a rising tide
of coherence and organization. The fledgling field of biodiversity informatics
looks set to deliver major advances that could turn the Internet into a giant
global biodiversity information system.
PMID- 11009409
TI - Interoperability of biodiversity databases: biodiversity information on every
desktop.
AB - Data about biodiversity are either scattered in many databases or reside on paper
or other media not amenable to interactive searching. The Global Biodiversity
Information Facility (GBIF) is a framework for facilitating the digitization of
biodiversity data and for making interoperable an as-yet-unknown number of
biodiversity databases that are distributed around the globe. In concert with
other existing efforts, GBIF will catalyze the completion of a Catalog of the
Names of Known Organisms and will develop search engines to mine the vast
quantities of biodiversity data. It will be an outstanding tool for scientists,
natural resource managers, and policy-makers.
PMID- 11009410
TI - Flashing superluminal components in the jet of the radio galaxy 3C120
AB - A 16-month sequence of radio images of the active galaxy 3C120 with the Very Long
Baseline Array reveals a region in the relativistic jet where superluminal
components flash on and off over time scales of months, while the polarization
angle rotates. This can be explained by interaction between the jet and an
interstellar cloud located about 8 parsecs from the center of the galaxy. The
cloud, which rotates the polarization direction and possibly eclipses a section
of the jet, represents a "missing link" between the ultradense broad-emission
line clouds closer to the center and the lower density narrow-emission-line
clouds seen on kiloparsec scales.
PMID- 11009411
TI - Quantum hall ferromagnetism in a two-dimensional electron system
AB - Experiments on a nearly spin degenerate two-dimensional electron system reveals
unusual hysteretic and relaxational transport in the fractional quantum Hall
effect regime. The transition between the spin-polarized (with fill fraction nu =
1/3) and spin-unpolarized (nu = 2/5) states is accompanied by a complicated
series of hysteresis loops reminiscent of a classical ferromagnet. In correlation
with the hysteresis, magnetoresistance can either grow or decay logarithmically
in time with remarkable persistence and does not saturate. In contrast to the
established models of relaxation, the relaxation rate exhibits an anomalous
divergence as temperature is reduced. These results indicate the presence of
novel two-dimensional ferromagnetism with a complicated magnetic domain dynamic.
PMID- 11009412
TI - Imaging coherent electron flow from a quantum point contact
AB - Scanning a charged tip above the two-dimensional electron gas inside a gallium
arsenide/aluminum gallium arsenide nanostructure allows the coherent electron
flow from the lowest quantized modes of a quantum point contact at liquid helium
temperatures to be imaged. As the width of the quantum point contact is
increased, its electrical conductance increases in quantized steps of 2 e(2)/h,
where e is the electron charge and h is Planck's constant. The angular dependence
of the electron flow on each step agrees with theory, and fringes separated by
half the electron wavelength are observed. Placing the tip so that it interrupts
the flow from particular modes of the quantum point contact causes a reduction in
the conductance of those particular conduction channels below 2 e(2)/h without
affecting other channels.
PMID- 11009413
TI - Technique for enhanced rare earth separation
AB - A process is demonstrated for the efficient separation of rare earth elements,
using a combination of selective reduction and vacuum distillation of halides.
The large differences in the redox chemistry of the rare earth elements and in
the vapor pressures of rare earth di- and trihalides are exploited for
separation. Experimental proof of concept is provided for the binary systems
praseodymium-neodymium and neodymium-samarium. This process enhances the
separation factor for the isolation of samarium and neodymium from their mixture
by more than an order of magnitude.
PMID- 11009414
TI - A mechanical model for intraplate earthquakes: application to the new madrid
seismic zone
AB - We present a time-dependent model for the generation of repeated intraplate
earthquakes that incorporates a weak lower crustal zone within an elastic
lithosphere. Relaxation of this weak zone after tectonic perturbations transfers
stress to the overlying crust, generating a sequence of earthquakes that
continues until the zone fully relaxes. Simulations predict large (5 to 10
meters) slip events with recurrence intervals of 250 to 4000 years and cumulative
offsets of about 100 meters, depending on material parameters and far-field
stress magnitude. Most are consistent with earthquake magnitude, coseismic slip,
recurrence intervals, cumulative offset, and surface deformation rates in the New
Madrid Seismic Zone. Computed interseismic strain rates may not be detectable
with available geodetic data, implying that low observed rates of strain
accumulation cannot be used to rule out future damaging earthquakes.
PMID- 11009415
TI - Dating of pore waters with (129)I: relevance for the origin of marine gas
hydrates
AB - Pore waters associated with gas hydrates at Blake Ridge in the Atlantic Ocean
were dated by measuring their iodine-129/iodine ratios. Samples collected from
sediments with ages between 1.8 and 6 million years ago consistently yield ages
around 55 million years ago. These ages, together with the strong iodine
enrichment observed in the pore waters, suggest that the origin of iodine is
related to organic material of early Tertiary age, which probably is also the
source of the methane in the gas hydrates at this location.
PMID- 11009416
TI - Polyploidy and the evolution of gender dimorphism in plants.
AB - Gender dimorphism and polyploidy are important evolutionary transitions that have
evolved repeatedly in many plant families. We show that gender dimorphism in
North American Lycium (Solanaceae) has evolved in polyploid, self-compatible taxa
whose closest relatives are cosexual, self-incompatible diploids. This has
occurred independently in South African Lycium. We present additional evidence
for this pathway to gender dimorphism from 12 genera involving at least 20
independent evolutionary events. We propose that polyploidy is a trigger of
unrecognized importance for the evolution of gender dimorphism, which operates by
disrupting self-incompatibility and leading to inbreeding depression.
Subsequently, male sterile mutants invade and increase because they are unable to
inbreed.
PMID- 11009417
TI - Alteration of stimulus-specific guard cell calcium oscillations and stomatal
closing in Arabidopsis det3 mutant.
AB - Cytosolic calcium oscillations control signaling in animal cells, whereas in
plants their importance remains largely unknown. In wild-type Arabidopsis guard
cells abscisic acid, oxidative stress, cold, and external calcium elicited
cytosolic calcium oscillations of differing amplitudes and frequencies and
induced stomatal closure. In guard cells of the V-ATPase mutant det3, external
calcium and oxidative stress elicited prolonged calcium increases, which did not
oscillate, and stomatal closure was abolished. Conversely, cold and abscisic acid
elicited calcium oscillations in det3, and stomatal closure occurred normally.
Moreover, in det3 guard cells, experimentally imposing external calcium-induced
oscillations rescued stomatal closure. These data provide genetic evidence that
stimulus-specific calcium oscillations are necessary for stomatal closure.
PMID- 11009418
TI - High direct estimate of the mutation rate in the mitochondrial genome of
Caenorhabditis elegans.
AB - Mutations in the mitochondrial genome have been implicated in numerous human
genetic disorders and offer important data for phylogenetic, forensic, and
population genetic studies. Using a long-term series of Caenorhabditis elegans
mutation accumulation lines, we performed a wide-scale screen for mutations in
the mitochondrial genome that revealed a mutation rate that is two orders of
magnitude higher than previous indirect estimates, a highly biased mutational
spectrum, multiple mutations affecting coding function, as well as mutational
hotspots at homopolymeric nucleotide stretches.
PMID- 11009419
TI - Resetting of circadian time in peripheral tissues by glucocorticoid signaling.
AB - In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus
of the brain, which harbors the central pacemaker, but also in most peripheral
tissues. Here, we show that the glucocorticoid hormone analog dexamethasone
induces circadian gene expression in cultured rat-1 fibroblasts and transiently
changes the phase of circadian gene expression in liver, kidney, and heart.
However, dexamethasone does not affect cyclic gene expression in neurons of the
suprachiasmatic nucleus. This enabled us to establish an apparent phase-shift
response curve specifically for peripheral clocks in intact animals. In contrast
to the central clock, circadian oscillators in peripheral tissues appear to
remain responsive to phase resetting throughout the day.
PMID- 11009420
TI - Dendritic computation of direction selectivity by retinal ganglion cells.
AB - Direction-selective ganglion cells (DSGCs) in the retina respond strongly when
stimulated by image motion in a preferred direction but are only weakly excited
by image motion in the opposite null direction. Such coding represents an early
manifestation of complex information processing in the visual system, but the
cellular locus and the synaptic mechanisms have yet to be elucidated. We recorded
the synaptic activity of DSGCs using strategies to observe the asymmetric
inhibitory inputs that underlie the generation of direction selectivity. The
critical nonlinear interactions between the excitatory and inhibitory inputs took
place postsynaptically within the dendrites of the DSGCs.
PMID- 11009421
TI - Failure to regulate TNF-induced NF-kappaB and cell death responses in A20
deficient mice.
AB - A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor kappaB (NF
kappaB) activity and tumor necrosis factor (TNF)-mediated programmed cell death
(PCD). TNF dramatically increases A20 messenger RNA expression in all tissues.
Mice deficient for A20 develop severe inflammation and cachexia, are
hypersensitive to both lipopolysaccharide and TNF, and die prematurely. A20
deficient cells fail to terminate TNF-induced NF-kappaB responses. These cells
are also more susceptible than control cells to undergo TNF-mediated PCD. Thus,
A20 is critical for limiting inflammation by terminating TNF-induced NF-kappaB
responses in vivo.
PMID- 11009422
TI - A specificity-enhancing factor for the ClpXP degradation machine.
AB - Events that stall bacterial protein synthesis activate the ssrA-tagging
machinery, resulting in resumption of translation and addition of an 11-residue
peptide to the carboxyl terminus of the nascent chain. This ssrA-encoded peptide
tag marks the incomplete protein for degradation by the energy-dependent ClpXP
protease. Here, a ribosome-associated protein, SspB, was found to bind
specifically to ssrA-tagged proteins and to enhance recognition of these proteins
by ClpXP. Cells with an sspB mutation are defective in degrading ssrA-tagged
proteins, demonstrating that SspB is a specificity-enhancing factor for ClpXP
that controls substrate choice.
PMID- 11009423
TI - Ubiquitin-activating/conjugating activity of TAFII250, a mediator of activation
of gene expression in Drosophila.
AB - Ubiquitination of histones has been linked to the complex processes that regulate
the activation of eukaryotic transcription. However, the cellular factors that
interpose this histone modification during the processes of transcriptional
activation are not well characterized. A biochemical approach identified the
Drosophila coactivator TAFII250, the central subunit within the general
transcription factor TFIID, as a histone-specific ubiquitin
activating/conjugating enzyme (ubac). TAFII250 mediates monoubiquitination of
histone H1 in vitro. Point mutations within the putative ubac domain of TAFII250
abolished H1-specific ubiquitination in vitro. In the Drosophila embryo,
inactivation of the TAFII250 ubac activity reduces the cellular level of
monoubiquitinated histone H1 and the expression of genes targeted by the maternal
activator Dorsal. Thus, coactivator-mediated ubiquitination of proteins within
the transactivation pathway may contribute to the processes directing activation
of eukaryotic transcription.
PMID- 11009425
TI - NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and
cachexia.
AB - MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair
of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappaB) is
activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal
muscle wasting in cachexia. Here, the role of NF-kappaB in cytokine-induced
muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced
activation of NF-kappaB inhibited SMD by suppressing MyoD mRNA at the
posttranscriptional level. In contrast, in differentiated myotubes, TNF plus
interferon-gamma (IFN-gamma) signaling was required for NF-kappaB-dependent down
regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down
regulated by TNF and IFN-gamma expression in mouse muscle in vivo. These data
elucidate a possible mechanism that may underlie the skeletal muscle decay in
cachexia.
PMID- 11009424
TI - Active remodeling of somatic nuclei in egg cytoplasm by the nucleosomal ATPase
ISWI.
AB - Cloning by the transplantation of somatic nuclei into unfertilized eggs requires
a dramatic remodeling of chromosomal architecture. Many proteins are specifically
lost from nuclei, and others are taken up from the egg cytoplasm. Recreating this
exchange in vitro, we identified the chromatin-remodeling nucleosomal adenosine
triphosphatase (ATPase) ISWI as a key molecule in this process. ISWI actively
erases the TATA binding protein from association with the nuclear matrix.
Defining the biochemistry of global nuclear remodeling may facilitate the
efficiency of cloning and other dedifferentiation events that establish new stem
cell lineages.
PMID- 11009426
TI - Increase of maximum life-span in Sweden, 1861-1999.
AB - A fundamental question in aging research is whether humans and other species
possess an immutable life-span limit. We examined the maximum age at death in
Sweden, which rose from about 101 years during the 1860s to about 108 years
during the 1990s. The pace of increase was 0.44 years per decade before 1969 but
accelerated to 1. 11 years per decade after that date. More than 70 percent of
the rise in the maximum age at death from 1861 to 1999 is attributable to
reductions in death rates above age 70. The rest are due to increased numbers of
survivors to old age (both larger birth cohorts and increased survivorship from
infancy to age 70). The more rapid rise in the maximum age since 1969 is due to
the faster pace of old-age mortality decline during recent decades.
PMID- 11009427
TI - Effects of chronic exercise on calcium signaling in rat vascular endothelium.
AB - Chronic exercise enhances endothelium-dependent vasodilating responses. To
investigate whether this is due to a change in endothelial Ca(2+) signaling, we
examined intracellular Ca(2+) concentration ([Ca(2+)](i)) level in rat aortic
endothelium in response to acetylcholine (ACh) or ATP. Four-week-old male Wistar
rats were divided into control and exercise groups. The exercised animals ran on
a treadmill at a moderate intensity for 60 min/day, 5 day/wk, for 10 wk. Rat
aortas were then excised and loaded with fura 2. After the aortas were mounted on
a flow chamber, these specimens were observed under an epifluorescence microscope
equipped with ratio-imaging capability. Our results showed that 1) chronic
exercise increased both ACh- and ATP-induced [Ca(2+)](i) responses; 2) ACh
induced heterogeneous [Ca(2+)](i) elevation in individual endothelial cells; and
3) the exercise effect on ACh-evoked endothelial [Ca(2+)](i) elevation was
inhibited by the Ca(2+) influx blocker SKF-96365, by a Ca(2+)-free buffer, or by
high concentrations of extracellular K(+). We conclude that chronic exercise
increases ACh-induced [Ca(2+)](i) elevation in rat aortic endothelium in situ,
possibly by facilitating Ca(2+) influx.
PMID- 11009428
TI - Aldose reductase inhibition alone or combined with an adenosine A(3) agonist
reduces ischemic myocardial injury.
AB - This study investigated whether aldose reductase (AR) inhibition with
zopolrestat, either alone or in combination with an adenosine A(3)-receptor
agonist (CB-MECA), reduced myocardial ischemic injury in rabbit hearts subjected
to 30 min of regional ischemia and 120 min of reperfusion. Zopolrestat reduced
infarct size by up to 61%, both in vitro (2 nM to 1 microM; EC(50) = 24 nM) and
in vivo (50 mg/kg). Zopolrestat reduced myocardial sorbitol concentration (index
of AR activity) by >50% (control, 15.0 +/- 2.2 nmol/g; 200 nM zopolrestat, 6.7 +/
1.3 nmol/g). A modestly cardioprotective concentration of CB-MECA (0.2 nM)
allowed a 50-fold reduction in zopolrestat concentration while providing a
similar reduction in infarct size (infarct area/area at risk: control, 62 +/- 2%;
1 microM zopolrestat, 24 +/- 5%; 20 nM zopolrestat plus 0.2 nM CB-MECA, 20 +/-
4%). In conclusion, AR inhibition is cardioprotective both in vitro and in vivo.
Furthermore, combining zopolrestat with an A(3) agonist allows a reduction in the
zopolrestat concentration while maintaining an equivalent degree of
cardioprotection.
PMID- 11009429
TI - C-peptide exerts cardioprotective effects in myocardial ischemia-reperfusion.
AB - Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes
(PMNs) results in cardiac dysfunction. C-peptide, a cleavage product of
proinsulin to insulin processing, induces nitric oxide (NO)-mediated
vasodilation. NO is reported to attenuate cardiac dysfunction caused by PMNs
after ischemia-reperfusion (I/R). Therefore, we hypothesized that C-peptide could
attenuate PMN-induced cardiac dysfunction. We examined the effects of C-peptide
in isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with
PMNs. C-peptide (70 nmol/kg iv) given 4 or 24 h before I/R significantly improved
coronary flow (P < 0.05), left ventricular developed pressure (LVDP) (P < 0.01),
and the maximal rate of development of LVDP (+dP/dt(max)) compared with I/R
hearts obtained from rats given 0.9% NaCl (P < 0.01). N(G)-nitro-L-arginine
methyl ester (L-NAME) (50 micromol/l) blocked these cardioprotective effects. In
addition, C-peptide significantly reduced cardiac PMN infiltration from 183 +/-
24 PMNs/mm(2) in untreated hearts to 44 +/- 10 and 58 +/- 25 PMNs/mm(2) in hearts
from 4- and 24-h C-peptide-treated rats, respectively. Rat PMN adherence to rat
superior mesenteric artery exposed to 2 U/ml thrombin was significantly reduced
in rats given C-peptide compared with rats given 0.9% NaCl (P < 0.001). Moreover,
C-peptide enhanced basal NO release from rat aortic segments. These results
provide evidence that C-peptide can significantly attenuate PMN-induced cardiac
contractile dysfunction in the isolated perfused rat heart subjected to I/R at
least in part via enhanced NO release.
PMID- 11009430
TI - Influence of erythrocyte aggregation on leukocyte margination in postcapillary
venules of rat mesentery.
AB - The role of erythrocyte (red blood cell; RBC) aggregation in affecting leukocyte
(white blood cell; WBC) margination in postcapillary venules of the mesentery
(rat) was explored by direct intravital microscopy. Optical techniques were
refined and applied to relate the light-scattering properties of RBCs to obtain a
quantitative index of aggregate size (G), which, under idealized conditions,
represents the number of RBCs per aggregate. WBC margination, defined as the
radial migration of WBCs to the venular wall and their subsequent rolling along
the endothelium, was measured as the percentage of the potentially maximal WBC
volumetric flux within the microvessel lumen (F(WBC)(*)). In normal blood,
F(WBC)(*) increased exponentially fourfold, and G increased from 1 to 1.15 as
wall shear rates () were reduced from a steady-state value of approximately 600
to <100 s(-1) by proximal occlusion with a blunt microprobe. Enhancement of
aggregation by infusion (iv) of dextran 500 (428 kDa), to attain a systemic
concentration of 3 g/100 ml, resulted in a four- and sevenfold increase in G and
F(WBC)(*), respectively, as was reduced below 100 s(-1). Inhibition of RBC
aggregation by infusion of dextran 40 (37.5 kDa) caused F(WBC)(*) to fall to one
half of its steady-state level for < 100 s(-1). Thus it appears that the well
known increase of WBC margination with reductions in is strongly dependent on the
occurrence of RBC aggregation. Increasing the extent of RBC aggregation during
reductions in also increased the firm adhesion of WBCs to the endothelium because
of an enhanced probability of contact between leukocytes and the postcapillary
venular wall.
PMID- 11009431
TI - Adenosine A(2a)-receptor activation increases contractility in isolated perfused
hearts.
AB - Adenosine A(2a)-receptor activation enhances shortening of isolated
cardiomyocytes. In the present study the effect of A(2a)-receptor activation on
the contractile performance of isolated rat hearts was investigated by recording
left ventricular pressure (LVP) and the maximal rate of LVP development
(+dP/dt(max)). With constant-pressure perfusion, adenosine caused concentration
dependent increases in LVP and +dP/dt(max), with detectable increases of 4.1 and
4.8% at 10(-6) M and maximal increases of 12.0 and 11.1% at 10(-4) M,
respectively. The contractile responses were prevented by the A(2a)-receptor
antagonists chlorostyryl-caffeine and aminofuryltriazolotriazinyl
aminoethylphenol (ZM-241385) but were not affected by the beta(1)-adrenergic
antagonist atenolol. The adenosine A(1)-receptor antagonist
dipropylcyclopentylxanthine and pertussis toxin potentiated the positive
inotropic effects of adenosine. The A(2a)-receptor agonists
ethylcarboxamidoadenosine and dimethoxyphenyl-methylphenylethyl-adenosine also
enhanced contractility. With constant-flow perfusion, 10(-5) M adenosine
increased LVP and +dP/dt(max) by 5.5 and 6.0%, respectively. In the presence of
the coronary vasodilator hydralazine, adenosine increased LVP and +dP/dt(max) by
7.5 and 7.4%, respectively. Dipropylcyclopentylxanthine potentiated the adenosine
contractile responses with constant-flow perfusion in the absence and presence of
hydralazine. These increases in contractile performance were also antagonized by
chlorostyryl-caffeine and ZM-241385. The results indicate that adenosine
increases contractile performance via activation of A(2a) receptors in the intact
heart independent of beta(1)-adrenergic receptor activation or changes in
coronary flow.
PMID- 11009432
TI - cADP ribose and [Ca(2+)](i) regulation in rat cardiac myocytes.
AB - cADP ribose (cADPR)-induced intracellular Ca(2+) concentration ([Ca(2+)](i))
responses were assessed in acutely dissociated adult rat ventricular myocytes
using real-time confocal microscopy. In quiescent single myocytes, injection of
cADPR (0.1-10 microM) induced sustained, concentration-dependent [Ca(2+)](i)
responses ranging from 50 to 500 nM, which were completely inhibited by 20 microM
8-amino-cADPR, a specific blocker of the cADPR receptor. In myocytes displaying
spontaneous [Ca(2+)](i) waves, increasing concentrations of cADPR increased wave
frequency up to approximately 250% of control. In electrically paced myocytes
(0.5 Hz, 5-ms duration), cADPR increased the amplitude of [Ca(2+)](i) transients
in a concentration-dependent fashion, up to 150% of control. Administration of 8
amino-cADPR inhibited both spontaneous waves as well as [Ca(2+)](i) responses to
electrical stimulation, even in the absence of exogenous cADPR. However,
subsequent [Ca(2+)](i) responses to 5 mM caffeine were only partially inhibited
by 8-amino-cADPR. In contrast, even under conditions where ryanodine receptor
(RyR) channels were blocked with ryanodine, high cADPR concentrations still
induced an [Ca(2+)](i) response. These results indicate that in cardiac myocytes,
cADPR induces Ca(2+) release from the sarcoplasmic reticulum through both RyR
channels and via mechanisms independent of RyR channels.
PMID- 11009433
TI - Improved energy homeostasis of the heart in the metabolic state of exercise.
AB - We postulate that metabolic conditions that develop systemically during exercise
(high blood lactate and high nonesterified fatty acids) are favorable for energy
homeostasis of the heart during contractile stimulation. We used working rat
hearts perfused at physiological workload and levels of the major energy
substrates and compared the metabolic and contractile responses to an acute low
to-high work transition under resting versus exercising systemic metabolic
conditions (low vs. high lactate and nonesterified fatty acids in the perfusate).
Glycogen preservation, resulting from better maintenance of high-energy
phosphates, was a consequence of improved energy homeostasis with high fat and
lactate. We explained the result by tighter coupling between workload and total
beta-oxidation. Total fatty acid oxidation with high fat and lactate reflected
increased availability of exogenous and endogenous fats for respiration, as
evidenced by increased long-chain fatty acyl-CoA esters (LCFA-CoAs) and by an
increased contribution of triglycerides to total beta-oxidation. Triglyceride
turnover (synthesis and degradation) also appeared to increase. Elevated LCFA
CoAs caused high total beta-oxidation despite increased malonyl-CoA. The
resulting bottleneck at mitochondrial uptake of LCFA-CoAs stimulated triglyceride
synthesis. Our results suggest the following. First, both malonyl-CoA and LCFA
CoAs determine total fatty acid oxidation in heart. Second, concomitant
stimulation of peripheral glycolysis and lipolysis should improve cardiac energy
homeostasis during exercise. We speculate that high lactate contributes to the
salutary effect by bypassing the glycolytic block imposed by fatty acids, acting
as an anaplerotic substrate necessary for high tricarbocylic acid cycle flux from
fatty acid-derived acetyl-CoA.
PMID- 11009434
TI - Endothelial adenosine transporter characterization in perfused guinea pig hearts.
AB - Adenosine (Ado), a smooth muscle vasodilator and modulator of cardiac function,
is taken up by many cell types via a saturable transporter, blockable by
dipyridamole. To quantitate the influences of endothelial cells in governing the
blood-tissue exchange of Ado and its concentration in the interstitial fluid, one
must define the permeability-surface area products (PS) for Ado via passive
transport through interendothelial gaps [PS(g)(Ado)] and across the endothelial
cell luminal membrane (PS(ecl)) in their normal in vivo setting. With the use of
the multiple-indicator dilution (MID) technique in Krebs-Ringer perfused,
isolated guinea pig hearts (preserving endothelial myocyte geometry) and by
separating Ado metabolites by HPLC, we found permeability-surface area products
for an extracellular solute, sucrose, via passive transport through
interendothelial gaps [PS(g)(Suc)] to be 1.9 +/- 0.6 ml. g(-1). min(-1) (n = 16
MID curves in 4 hearts) and took PS(g)(Ado) to be 1. 2 times PS(g)(Suc). MID
curves were obtained with background nontracer Ado concentrations up to 800
micrometer, partially saturating the transporter and reducing its effective
PS(ecl) for Ado. The estimated maximum value for PS(ecl) in the absence of
background adenosine was 1.1 +/- 0.1 ml. g(-1). min(-1) [maximum rate of
transporter conformational change to move the substrate from one side of the
membrane to the other (maximal velocity; V(max)) times surface area of 125 +/- 11
nmol. g(-1). min(-1)], and the Michaelis-Menten constant (K(m)) was 114 +/- 12
microM, where +/- indicates 95% confidence limits. Physiologically, only high Ado
release with hypoxia or ischemia will partially saturate the transporter.
PMID- 11009435
TI - Mechanisms of endothelial cell swelling from lactacidosis studied in vitro.
AB - One of the early sequelae of ischemia is an increase of circulating lactic acid
that occurs in response to anaerobic metabolism. The purpose of the present study
was to investigate whether lactic acidosis can induce endothelial swelling in
vitro under closely controlled extracellular conditions. Cell volume of suspended
cultured bovine aortic endothelial cells was measured by use of an advanced
Coulter technique employing the "pulse area analysis" signal-processing technique
(CASY1). The isosmotic reduction of pH from 7.4 to 6.8 had no effect on cell
volume. Lowering of pH to 6.6, 6.4, or 6.0, however, led to significant, pH
dependent increases of cell volume. Swelling was more pronounced in bicarbonate
buffered media than in HEPES buffer. Specific inhibition of Na(+)/H(+) exchange
by ethylisopropylamiloride completely prevented swelling in HEPES-buffered media.
Pretreatment with ouabain to partially depolarize the cells did not affect the
degree of acidosis-induced swelling. In bicarbonate-buffered media, the
inhibition of transmembrane HCO(3)(-) transport by DIDS reduced swelling to a
level comparable with that seen in the absence of bicarbonate ions. Lactacidosis
induced endothelial swelling, therefore, is a result of intracellular pH
regulatory mechanisms, namely, Na(+)/H(+) exchange and bicarbonate-transporting
carriers.
PMID- 11009436
TI - Transarterial wall oxygen gradients at the deployment site of an intra-arterial
stent in the rabbit.
AB - Intimal hyperplasia, common at the deployment site of an intra-arterial stent,
may be caused by artery wall hypoxia. The purpose of this study was to determine
the effect of an intra-arterial stent on artery wall oxygen concentrations.
Transarterial wall oxygen gradients were measured by microelectrode at stent
deployment sites in New Zealand White rabbits. Thinned artery walls and decreased
oxygen tensions were noted throughout the artery wall immediately following stent
deployment with a return toward control values at 28 days. Angioplasty alone had
no acute effect on artery wall oxygen concentrations. Larger stent deployment
diameters yielded acutely lower artery wall oxygen tensions. Using a linear one
dimensional model for the oxygen profile, we noted that stent deployment resulted
in acute changes in oxygen consumption in the inner artery wall that rapidly
returned to control values. Changes were noted without differences in blood
pressure or arterial blood oxygen concentrations. Oxygen delivery to and
consumption within the artery wall are altered by intra-arterial stent
deployment. A role for artery wall hypoxia in artery wall pathology at the
deployment site of an intra-arterial stent is supported by these findings.
PMID- 11009437
TI - Hypoxic pulmonary vasoconstriction is modified by P-450 metabolites.
AB - 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 4A (CYP4A)
metabolite of arachidonic acid (AA) in human and rabbit lung microsomes and is a
dilator of isolated human pulmonary arteries (PA). However, little is known
regarding the contribution of P-450 metabolites to pulmonary vascular tone. We
examined 1) the effect of two mechanistically distinct omega- and omega1
hydroxylase inhibitors on perfusion pressures in isolated rabbit lungs ventilated
with normoxic or hypoxic gases, 2) changes in rabbit PA ring tone elicited by 20
HETE or omega- and omega1-hydroxylase inhibitors, and 3) expression of CYP4A
protein in lung tissue. A modest increase in perfusion pressure (55 +/- 11% above
normoxic conditions) was observed in isolated perfused lungs during ventilation
with hypoxic gas (FI(O(2)) = 0.05). Inhibitors of 20-HETE synthesis, 17
oxydecanoic acid (17-ODYA) or N-methylsulfonyl-12,12-dibromododec-11-enamide
(DDMS), increased baseline perfusion pressure above that of vehicle and amplified
hypoxia-induced increases in perfusion pressures by 92 +/- 11% and 105 +/- 11%
over baseline pressures, respectively. 20-HETE relaxed phenylephrine (PE)
constricted PA rings. Treatment with 17-ODYA enhanced PE-induced contraction of
PA rings, consistent with inhibition of a product that promotes arterial
relaxation, whereas 6-(20-propargyloxyphenyl)hexanoic acid (PPOH), an epoxygenase
inhibitor, blunted contraction to PE. Conversion of AA into 20-HETE was blocked
by 17-ODYA, DDMS, and hypoxia. CYP4A immunospecific protein confirms expression
of CYP4A in male rabbit lung tissue. Our data suggest that endogenously produced
20-HETE could modify rabbit pulmonary vascular tone, particularly under hypoxic
conditions.
PMID- 11009438
TI - Alterations in myocardial collagen content affect rat papillary muscle function.
AB - We investigated the influence of myocardial collagen volume fraction (CVF, %) and
hydroxyproline concentration (microg/mg) on rat papillary muscle function.
Collagen excess was obtained in 10 rats with unilateral renal ischemia for 5 wk
followed by 3-wk treatment with ramipril (20 mg. kg(-1). day(-1)) (RHTR rats; CVF
= 3.83 +/- 0. 80, hydroxyproline = 3.79 +/- 0.50). Collagen degradation was
induced by double infusion of oxidized glutathione (GSSG rats; CVF = 2.45 +/-
0.52, hydroxyproline = 2.85 +/- 0.18). Nine untreated rats were used as controls
(CFV = 3.04 +/- 0.58, hydroxyproline = 3.21 +/- 0.30). Active stiffness (AS; g.
cm(-2). %L(max)(-1)) and myocyte cross-sectional area (MA; micrometer(2)) were
increased in the GSSG rats compared with controls [AS 5.86 vs. 3.96 (P < 0.05);
MA 363 +/- 59 vs. 305 +/- 28 (P < 0.05)]. In GSSG and RHTR groups the passive
tension-length curves were shifted downwards, indicating decreased passive
stiffness, and upwards, indicating increased passive stiffness, respectively.
Decreased collagen content induced by GSSG is related to myocyte hypertrophy,
decreased passive stiffness, and increased AS, and increased collagen
concentration causes myocardial diastolic dysfunction with no effect on systolic
function.
PMID- 11009439
TI - Matrix metalloproteinase activity is required for activity-induced angiogenesis
in rat skeletal muscle.
AB - Proteolysis of the capillary basement membrane is a hallmark of inflammation
mediated angiogenesis, but it is undetermined whether proteolysis plays a
critical role in the process of activity-induced angiogenesis. Matrix
metalloproteinases (MMPs) constitute the major class of proteases responsible for
degradation of basement membrane proteins. We observed significant elevations of
mRNA and protein levels of both MMP-2 and membrane type 1 (MT1)-MMP (2.9 +/- 0.7-
and 1.5 +/- 0.1-fold above control, respectively) after 3 days of chronic
electrical stimulation of rat skeletal muscle. Inhibition of MMP activity via the
inhibitor GM-6001 prevented the growth of new capillaries as assessed by the
capillary-to-fiber ratio (1.34 +/- 0.08 in GM-6001-treated muscles compared with
1.69 +/- 0.03 in control 7-day-stimulated muscles). This inhibition correlated
with a significant reduction in the number of capillaries with observable breaks
in the basement membrane, as assessed by electron microscopy (0.27 +/- 0.27% in
GM-6001-treated muscles compared with 3.72 +/- 0.65% in control stimulated
muscles). Proliferation of capillary-associated cells was significantly elevated
by 2 days and remained elevated throughout 14 days of stimulation. Capillary
associated cell proliferation during muscle stimulation was not affected by MMP
inhibition (80.3 +/- 9.3 nuclei in control and 63.5 +/- 8.5 nuclei in GM-6001
treated animals). We conclude that MMP proteolysis of capillary basement membrane
proteins is a critical component of physiological angiogenesis, and we postulate
that capillary-associated proliferation precedes and occurs independently of
endothelial cell sprout formation.
PMID- 11009440
TI - Orthostatic hypotension in aging humans.
AB - We tested the hypothesis that hypotension occurred in older adults at the onset
of orthostatic challenge as a result of vagal dysfunction. Responses of heart
rate (HR) and mean arterial pressure (MAP) were compared between 10 healthy older
and younger adults during onset and sustained lower body negative pressure
(LBNP). A younger group was also assessed after blockade of the parasympathetic
nervous system with the use of atropine or glycopyrrolate and after blockade of
the beta(1)-adrenoceptor by use of metoprolol. Baseline HR (older vs. younger: 59
+/- 4 vs. 54 +/- 1 beats/min) and MAP (83 +/- 2 vs. 89 +/- 3 mmHg) were not
significantly different between the groups. During -40 Torr, significant
tachycardia occurred at the first HR response in the younger subjects without
hypotension, whereas significant hypotension [change in MAP (DeltaMAP) -7 +/- 2
mmHg] was observed in the elderly without tachycardia. After the parasympathetic
blockade, tachycardiac responses of younger subjects were diminished and
associated with a significant hypotension at the onset of LBNP. However, MAP was
not affected after the cardiac sympathetic blockade. We concluded that the
elderly experienced orthostatic hypotension at the onset of orthostatic challenge
because of a diminished HR response. However, an augmented vasoconstriction
helped with the maintenance of their blood pressure during sustained LBNP.
PMID- 11009441
TI - IL-10 deficiency increases superoxide and endothelial dysfunction during
inflammation.
AB - Little is known about the role of interleukin-10 (IL-10), an anti-inflammatory
cytokine, in blood vessels. We used IL-10-deficient mice (IL-10 -/-) to examine
the hypothesis that IL-10 protects endothelial function after lipopolysaccharide
(LPS) treatment. The responses of carotid arteries were studied in vitro 6 h
after injection of a relatively low dose of LPS (10 microgram ip). In IL-10 -/-
mice, the maximum relaxation to ACh (3 microM) was 56 +/- 6% (means +/- SE) after
LPS injection and 84 +/- 4% after vehicle injection (P < 0.05). Thus endothelium
dependent relaxation was impaired in carotid arteries from IL-10 -/- mice after
LPS injection. In contrast, this dose of LPS did not alter relaxation to ACh in
vessels from wild-type (IL-10 +/+) mice. Relaxation to nitroprusside and
papaverine was similar in arteries from both IL-10 -/- and IL-10 +/+ mice after
vehicle or LPS injection. Because inflammation is associated with increased
levels of reactive oxygen species, we also tested the hypothesis that superoxide
contributes to the impairment of endothelial function by LPS in the absence of IL
10. Results using confocal microscopy and hydroethidine indicated that levels of
superoxide are elevated in carotid arteries from IL-10 -/- mice compared with IL
10 +/+ mice after LPS injection. The impaired relaxation of arteries from IL-10
/- mice after LPS injection was restored to normal by polyethylene glycol
suspended superoxide dismutase (50 U/ml) or allopurinol (1 mM), an inhibitor of
xanthine oxidase. These data provide direct evidence that IL-10 protects
endothelial function after an acute inflammatory stimulus by limiting local
increases in superoxide. The source of superoxide in this model may be xanthine
oxidase.
PMID- 11009442
TI - Na(+)/H(+) exchange inhibition-induced cardioprotection in dogs: effects on
neutrophils versus cardiomyocytes.
AB - Numerous studies have examined the effect of Na(+)/H(+) exchanger (NHE)
inhibition on the myocardium; however, the effect of NHE-1 inhibition on
neutrophil function has not been adequately examined. An in vivo canine model of
myocardial ischemia-reperfusion injury in which 60 min of left anterior
descending coronary artery occlusion followed by 3 h of reperfusion was used to
examine the effect of NHE-1 inhibition on infarct size (IS) and neutrophil
function. BIIB-513, a selective inhibitor of NHE-1, was infused before ischemia.
IS was expressed as a percentage of area at risk (IS/AAR). NHE-1 inhibition
significantly reduced IS/AAR and reduced neutrophil accumulation in the ischemic
myocardium. NHE-1 inhibition attenuated both phorbol 12-myristate 13-acetate- and
platelet-activating factor-induced neutrophil respiratory burst but not CD18
upregulation. Furthermore, NHE-1 inhibition directly protected cardiomyocytes
against metabolic inhibition-induced lactate dehydrogenase release and
hypercontracture. This study provides evidence that the cardioprotection induced
by NHE-1 inhibition is likely due to specific protection of cardiomyocytes and
attenuation of neutrophil activity.
PMID- 11009443
TI - Three-week neonatal hypoxia reduces blood CGRP and causes persistent pulmonary
hypertension in rats.
AB - To increase understanding of persistent pulmonary hypertension, we examined
chronic pulmonary effects of hypoxia at birth and their relationships with
immunoreactive levels of the potent vasodilator, calcitonin gene-related peptide
(CGRP). Rats were born in 10% hypobaric hypoxia, where they remained for 1-2
days, or in 15% hypoxia, where they remained for 21 days. All were then reared in
normoxia for 3 mo followed by reexposure to 10% hypoxia for 7 days (H-->H) or
continued normoxia (H-->N); age-matched normoxic rats were hypoxic for the last 7
days (N-->H) or normoxic throughout (N-->N). Results are as follows. Pulmonary
arterial pressure (P(PA)) in 10% H-->N rats was normal at the end of the
experiment (13 wk), but in rats reexposed to hypoxia (H-->H), pressure rose to
19% above N-->H controls. In 15% H-->N rats, P(PA) remained high, similar to that
of N-->H rats, and increased further by 40% on reexposure (H-->H). Medial
thickness of small pulmonary arteries in 10% H-->H rats also increased by 40%
over N-->H controls and was equally high in 15% H-->N and H-->H rats. In N-->H
rats from both experiments, right ventricular hypertrophy index (RVH) was
increased after hypoxia at 15-16 wk. Also, in the 15% study, RVH remained
elevated in H-->N rats and increased in H-->H rats by 19% above N-->H controls.
Blood CGRP was reduced by neonate and adult hypoxia, and hypoxic reexposure (H-
>H) further lowered blood CGRP in the 15% but not 10% study. Declining left
ventricular blood CGRP correlated highly with logarithmically increasing P(PA) in
the 15% study (r = -0.81, P = 0.000). In conclusion, 1) short perinatal exposure
to 10% O(2) exacerbated pulmonary hypertension with hypoxia later in life, 2) 15%
O(2) at birth and for 21 days caused persistent pulmonary hypertension and
exacerbation with reexposure, and 3) P(PA) correlated highly with declining blood
CGRP levels in the 15% study.
PMID- 11009444
TI - Virtual sources associated with linear and curved strands of cardiac cells.
AB - Transmembrane potential (V(m)) responses in cardiac strands with different
curvature were characterized during uniform electric-field stimulation with the
use of modeling and experimental approaches. Linear and U-shaped strands (width
100-150 micrometer) were stained with voltage-sensitive dye. V(m) was measured by
optical mapping across the width and at sites of beginning curvature. Field
pulses were applied transverse to the strands during the action-potential
plateau. For linear strands, V(m) contained 1) a rapid passive component
(V(m)(ar)) nearly linear and symmetric across the width, 2) a slower
hyperpolarizing component (V(m)(as)) greater and faster on the anodal side, and
3) at high field strengths a delayed depolarizing component (V(m)(ad)) greater on
the anodal side. For U-shaped strands, V(m) at sites of beginning curvature also
contained rapid and slow components (V(m)(br) and V(m)(bs), respectively) that
included contributions from the linear strand response and from the fiber
curvature. V(m)(ar), V(m)(br), and part of V(m)(bs) could be attributed to
passive behavior that was modeled, and V(m)(as), V(m)(ad), and part of V(m)(bs)
could be attributed to active membrane currents. Thus curved strands exhibit
field responses separable into components with characteristic amplitude, spatial,
and temporal signatures.
PMID- 11009445
TI - Skin microvascular adaptations during maturation and aging of hairless mice.
AB - Using intravital fluorescence microscopy in the ears of hairless mice, we
determined skin microvascular adaptations during the process of aging from
juvenile to adult and senescent life (6-78 wk). Despite an increase of ear area
within the first 36 wk, the number and branching pattern of both arteriolar and
venular microvessels remained constant during the whole life period. Both
arterioles and venules exhibited an increase in length, diameter, and
intervascular distance up to the age of 36 wk. With the increase of the size of
the ears, the observation that cutaneous capillary density remained unchanged
implied new capillary formation. During aging to 78 wk, capillary density in the
ears was reduced to approximately 40%. Functional analysis revealed an
appropriate hyperemic response to a 2-min period of ischemia during late juvenile
and adult life, which, however, was markedly reduced during senescence. Thus,
except for capillaries, there is no indication for age-related new vessel
formation. The process of aging from adult to senescent life does not cause any
significant remodeling but is associated with a decrease of nutritive perfusion
and a functional impairment to respond to stimuli such as ischemia.
PMID- 11009446
TI - Effect of hypercholesterolemia on Ca(2+)-dependent K(+) channel-mediated
vasodilatation in vivo.
AB - Nitric oxide (NO)-mediated and NO-independent mechanisms of endothelium-dependent
vasodilatation involve Ca(2+)-dependent K(+) (K(Ca)) channels. We examined the
role in vivo of K(Ca) channels in NO-independent vasodilatation in
hypercholesterolemia. Hindlimb vascular conductance was measured at rest and
after aortic injection of ACh, bradykinin (BK), and sodium nitroprusside in
anesthetized control and cholesterol-fed rabbits. Conductances were measured
before and after treatment with the NO synthase antagonist N(omega)-nitro-L
arginine methyl ester (L-NAME, 10 mg/kg) or K(Ca) blockers tetraethylammonium (30
mg/kg), charybdotoxin (10 microgram/kg), and apamin (50 microgram/kg). The
contribution of NO to basal conductance was greater in control than in
cholesterol-fed rabbits [2.2 +/- 0.4 vs. 1.1 +/- 0.3 (SE) ml. min(-1). kg(-1).
100 mmHg(-1), P < 0.05], but the NO-independent K(Ca) channel-mediated component
was greater in the cholesterol-fed than in the control group (1.1 + 0.4 vs. 0.3
+/- 0.1 ml. min(-1). kg(-1). 100 mmHg(-1), P < 0.05). Maximum conductance
response to ACh and BK was less in cholesterol-fed than in control rabbits, and
the difference persisted after L-NAME (ACh: 7.7 +/- 0.7 vs. 10.1 +/- 0.5 ml. min(
1). kg(-1). 100 mmHg(-1), P < 0.005). Blockade of K(Ca) channels with
tetraethylammonium or charybdotoxin + apamin almost completely abolished L-NAME
resistant vasodilatation after ACh or BK. The magnitude of K(Ca)-mediated
vasodilatation after ACh or BK was impaired in hypercholesterolemic rabbits.
Vasodilator responses to nitroprusside did not differ between groups. In vivo,
hypercholesterolemia is associated with an altered balance between NO-mediated
and NO-independent K(Ca) channel contributions to resting vasomotor tone and
impairment of both mechanisms of endothelium-dependent vasodilatation.
PMID- 11009447
TI - K(ATP) channel activation reduces the severity of postresuscitation myocardial
dysfunction.
AB - Postresuscitation myocardial dysfunction has been recognized as a leading cause
of the high postresuscitation mortality rate. We investigated the effects of
ischemic preconditioning and activation of ATP-sensitive K(+) (K(ATP)) channels
on postresuscitation myocardial function. Ventricular fibrillation (VF) was
induced in 25 Sprague-Dawley rats. Cardiopulmonary resuscitation (CPR), including
mechanical ventilation and precordial compression, was initiated after 4 min of
untreated VF. Defibrillation was attempted after 6 min of CPR. The animals were
randomized to five groups treated with 1) ischemic preconditioning, 2) K(ATP)
channel opener, 3) ischemic preconditioning with K(ATP) channel blocker
administered 1 min after VF, 4) K(ATP) channel blocker administered 45 min before
induction of ischemic preconditioning, and 5) placebo. Postresuscitation
myocardial function, as measured by the rate of left ventricular pressure
increase at 40 mmHg, the rate of left ventricular decline, cardiac index, and
duration of survival, was significantly improved in both preconditioned and
K(ATP) channel opener-treated animals. K(ATP) channel blocker administered 45 min
before induction of ischemic preconditioning completely abolished the myocardial
protective effects of preconditioning. We conclude that ischemic preconditioning
significantly improved post-CPR myocardial function and survival. These results
also provide evidence that the myocardial protective effects of ischemic
preconditioning are mediated by K(ATP) channel activation.
PMID- 11009448
TI - P-450 epoxygenase and NO synthase inhibitors reduce cerebral blood flow response
to N-methyl-D-aspartate.
AB - Epoxyeicosatrienoic acids are cerebral vasodilators produced in astrocytes by
cytochrome P-450 epoxygenase activity. The P-450 inhibitor miconazole attenuates
the increase in cerebral blood flow (CBF) elicited by glutamate. We evaluated
whether epoxygenase activity is involved in the CBF response to activation of the
N-methyl-D-aspartate (NMDA) receptor subtype by using two structurally distinct
inhibitors, miconazole and N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide
(MS-PPOH), a selective epoxygenase substrate inhibitor. Drugs were delivered
locally through microdialysis probes in striata of anesthetized rats. Local CBF
was measured by hydrogen clearance and compared with CBF in contralateral
striatum receiving vehicle. Microdialysis perfusion of NMDA doubled CBF and
increased nitric oxide (NO) production estimated by recovery of labeled
citrulline in the dialysate during labeled arginine infusion. Perfusion of
miconazole or MS-PPOH blocked the increase in CBF without decreasing citrulline
recovery. Perfusion of N(omega)-nitro-L-arginine decreased baseline CBF and
inhibited the CBF response to NMDA. Perfusion of MS-PPOH did not inhibit the CBF
response to sodium nitroprusside. We conclude that both the P-450 epoxygenase and
NO synthase pathways are involved in the local CBF response to NMDA receptor
activation, and that the signaling pathway may be more complex than simply NO
diffusion from neurons to vascular smooth muscle.
PMID- 11009449
TI - VEGF and ATP act by different mechanisms to increase microvascular permeability
and endothelial [Ca(2+)](i).
AB - Vascular endothelial growth factor (VEGF) increases hydraulic conductivity (L(p))
by stimulating Ca(2+) influx into endothelial cells. To determine whether VEGF
mediated Ca(2+) influx is stimulated by release of Ca(2+) from intracellular
stores, we measured the effect of Ca(2+) store depletion on VEGF-mediated
increased L(p) and endothelial intracellular Ca(2+) concentration ([Ca(2+)](i))
of frog mesenteric microvessels. Inhibition of Ca(2+) influx by perfusion with
NiCl(2) significantly attenuated VEGF-mediated increased [Ca(2+)](i). Depletion
of Ca(2+) stores by perfusion of vessels with thapsigargin did not affect the
VEGF-mediated increased [Ca(2+)](i) or the increase in L(p). In contrast, ATP
mediated increases in both [Ca(2+)](i) and L(p) were inhibited by thapsigargin
perfusion, demonstrating that ATP stimulated store-mediated Ca(2+) influx. VEGF
also increased Mn(2+) influx after perfusion with thapsigargin, whereas ATP did
not. These data showed that VEGF increased [Ca(2+)](i) and L(p) even when Ca(2+)
stores were depleted and under conditions that prevented ATP-mediated increases
in [Ca(2+)](i) and L(p). This suggests that VEGF acts through a Ca(2+) store
independent mechanism, whereas ATP acts through Ca(2+) store-mediated Ca(2+)
influx.
PMID- 11009450
TI - Significance of ERK cascade compared with JAK/STAT and PI3-K pathway in gp130
mediated cardiac hypertrophy.
AB - We compared the role of the Raf-1/mitogen-activated protein kinase/extracellular
signal-regulated protein kinase (MEK)/extracellular signal-regulated protein
kinase (ERK)/p90(RSK) cascade in gp130-mediated cardiac hypertrophy with the
contribution of the Janus kinase (JAK)/signal transduction and activation of
transcription (STAT) and phosphatidylinositide 3-kinase (PI3-K) pathways. Primary
cultured neonatal rat cardiomyocytes were stimulated with leukemia inhibitory
factor (LIF). LIF sequentially activated Raf-1, MEK1/2, ERK1/2, and p90(RSK). We
used PD-98059 (a specific MEK inhibitor), AG-490 (a JAK2 inhibitor), and
wortmannin (a PI3-K inhibitor) to confirm that this cascade was independent of
the JAK/STAT and PI3-K/p70 S6 kinase (S6K) pathways. PD-98059, AG-490, and
wortmannin suppressed the LIF-induced increase in [(3)H]phenylalanine uptake by
54.7, 21.5, and 25.6%, respectively, and inhibited the increase in cell area by
61.2, 42.8, and 39.2%, respectively. Reorganization of myofilaments was
predominantly suppressed by AG-490. LIF-induced expression of c-fos, brain
natriuretic peptide, and skeletal alpha-actin mRNA was markedly suppressed by PD
98059 and moderately suppressed by wortmannin and AG-490. Atrial natriuretic
peptide was significantly suppressed by AG-490. These findings indicate that this
pathway is critically involved in protein synthesis, induction of c-fos, brain
natriuretic peptide, and skeletal alpha-actin expression and is partially
involved in myofilament reorganization and atrial natriuretic peptide induction
in gp130-mediated cardiac hypertrophy.
PMID- 11009451
TI - Model of structural and functional adaptation of small conductance vessels to
arterial hypotension.
AB - Vascular networks adapt structurally in response to local pressure and flow and
functionally in response to the changing needs of tissue. Whereas most research
has either focused on adaptation of the macrocirculation, which primarily
transports blood, or the microcirculation, which primarily controls flow, the
present work addresses adaptation of the small conductance vessels in between,
which both conduct blood and resist flow. A simple hemodynamic model is
introduced consisting of three parts: 1) bifurcating arterial and venous trees,
2) an empirical description of the microvasculature, and 3) a target shear stress
depending on pressure. This simple model has the minimum requirements to explain
qualitatively the observed structure in normotensive conditions. It illustrates
that flow regulation in the microvasculature makes adaptation in the larger
conductance vessels stable. Furthermore, it suggests that structural changes in
response to hypotension can account for the observed decrease in the lower limit
of autoregulation in chronically hypotensive vasculature. Independent adaptation
to local conditions thus yields a coordinated set of structural changes that
ultimately adapts supply to demand.
PMID- 11009452
TI - Mechanisms of calcitonin gene-related peptide-induced increases of pulmonary
blood flow in fetal sheep.
AB - Fetal pulmonary blood flow is regulated by various vasoactive substances. One,
calcitonin gene-related peptide (CGRP), increases pulmonary blood flow. We
examined four key physiological mechanisms underlying this response using the
blocker drugs CGRP receptor blocker (CGRP(8-37)), nitric oxide synthase inhibitor
[N(omega)-nitro-L-arginine (L-NNA)], adenosine triphosphate-dependent potassium
(K(ATP)) channel blocker (glibenclamide), and cyclooxygenase inhibitor
(indomethacin) in 17 near-term fetal sheep. Catheters were placed in the left
(LPA) and main pulmonary arteries, and an ultrasonic flow transducer was placed
around the LPA to measure flow continuously. CGRP was injected directly into the
LPA (mean 1.02 microgram/kg) before and after blockade, and responses to CGRP
were statistically compared. Before blockade, CGRP increased LPA blood flow from
23 +/- 25 to 145 +/- 77 ml/min (means +/- SD), and these increases were
significantly attenuated by CGRP(8-37) (n = 6; 91% inhibition), L-NNA (n = 6; 86%
inhibition), and glibenclamide (n = 6; 69% inhibition). No significant changes
were found with indomethacin (n = 6; 4% inhibition). Thus, in the fetal pulmonary
circulation, CGRP increases pulmonary blood flow not only through its specific
receptor but also, in part, through nitric oxide release and K(ATP) channel
activation.
PMID- 11009453
TI - Role of protein kinase C in alpha(1)-adrenergic regulation of a(Na)(i) in guinea
pig ventricular myocytes.
AB - We investigated the role of protein kinase C (PKC) in alpha(1)-adrenergic
regulation of intracellular Na(+) activity (a(Na)(i)) in single guinea pig
ventricular myocytes. a(Na)(i) and membrane potentials were measured with the
Na(+)-sensitive indicator sodium-binding benzofuran isophthalate and conventional
microelectrodes, respectively, at room temperature (24-26 degrees C) while
myocytes were stimulated at a rate of 0.25-0.3 Hz. The PKC activator 4beta
phorbol 12-myristate 13-acetate (PMA) decreased a(Na)(i) in a concentration
dependent manner. PMA (100 nM) produced a maximal decrease in a(Na)(i) of 1.5 mM
from 6.5 +/- 0.4 to 5.0 +/- 0.4 mM (means +/- SE, n = 12, P < 0.01). The PMA
concentration required for a half-maximal decrease in a(Na)(i) was 0.46 +/- 0.13
nM (n = 3, P < 0.01). An inactive phorbol, 4alpha-phorbol 12-myristate 13
acetate, did not decrease a(Na)(i). The decrease caused by PMA could be blocked
by the PKC inhibitors staurosporine and bisindolylmaleimide I (GF-109203X).
Stimulation of the alpha(1)-adrenoceptor with 50 microM phenylephrine decreased
a(Na)(i) from 6.1 +/- 0.3 to 4.6 +/- 0.3 mM (n = 11, P < 0.01). The decrease in
a(Na)(i) produced by phenylephrine was blocked by pretreatment with
staurosporine, GF-109203X, or PMA. The decrease in a(Na)(i) produced by PMA was
not prevented by pretreatment with tetrodotoxin but was blocked by pretreatment
with strophanthidin or high extracellular K(+) concentration. The results suggest
that alpha(1)-adrenergic receptor activation results in a decrease in a(Na)(i)
via PKC-induced stimulation of the Na(+)-K(+) pump in cardiac myocytes.
PMID- 11009454
TI - Nonlinear dynamics of heart rate variability during experimental hemorrhage in
ketamine-anesthetized rats.
AB - Indexes of heart rate variability (HRV) based on linear stochastic models are
independent risk factors for arrhythmic death (AD). An index based on a nonlinear
deterministic model, a reduction in the point correlation dimension (PD2i), has
been shown in both animal and human studies to have a higher sensitivity and
specificity for predicting AD. Dimensional reduction subsequent to transient
ischemia was examined previously in a simple model system, the intrinsic nervous
system of the isolated rabbit heart. The present study presents a new model
system in which the higher cerebral centers are blocked chemically (ketamine
inhibition of N-methyl-D-aspartate receptors) and the system is perturbed over a
longer 15-min interval by continuous hemorrhage. The hypothesis tested was that
dimensional reduction would again be evoked, but in association with a more
complex relationship between the system variables. The hypothesis was supported,
and we interpret the greater response complexity to result from the larger
autonomic superstructure attached to the heart. The complexities observed in the
nonlinear heartbeat dynamics constitute a new genre of autonomic response, one
clearly distinct from a hardwired reflex or a cerebrally determined defensive
reaction.
PMID- 11009455
TI - PKCepsilon modulates NF-kappaB and AP-1 via mitogen-activated protein kinases in
adult rabbit cardiomyocytes.
AB - We have previously shown that protein kinase C (PKC)-epsilon, nuclear factor (NF)
kappaB, and mitogen-activated protein kinases (MAPKs) are essential signaling
elements in ischemic preconditioning. In the present study, we examined whether
activation of PKCepsilon affects the activation of NF-kappaB in cardiac myocytes
and whether MAPKs are mediators of this signaling event. Activation of PKCepsilon
(+108% above control) in adult rabbit cardiomyocytes to a degree that has been
previously shown to protect myocytes against hypoxic injury increased the DNA
binding activity of NF-kappaB (+164%) and activator protein (AP)-1 (+127%) but
not that of Elk-1. Activation of PKCeta did not have an effect on these
transcription factors. Activation of PKCepsilon also enhanced the phosphorylation
activities of the p44/p42 MAPKs and the p54/p46 c-Jun NH(2)-terminal kinases
(JNKs). PKCepsilon-induced activation of NF-kappaB and AP-1 was completely
abolished by inhibition of the p44/p42 MAPK pathway with PD98059 and by
inhibition of the p54/p46 JNK pathway with a dominant negative mutant of MAPK
kinase-4, indicating that both signaling pathways are necessary. Taken together,
these data identify NF-kappaB and AP-1 as downstream targets of PKCepsilon,
thereby establishing a molecular link between activation of PKCepsilon and
activation of NF-kappaB and AP-1 in cardiomyocytes. The results further
demonstrate that both the p44/p42 MAPK and the p54/p46 JNK signaling pathways are
essential mediators of this event.
PMID- 11009456
TI - Cardioprotection by K(ATP) channels in wild-type hearts and hearts overexpressing
A(1)-adenosine receptors.
AB - We studied the role of mitochondrial ATP-sensitive K(+) (K(ATP)) channels in
modifying functional responses to 20 min global ischemia and 30 min reperfusion
in wild-type mouse hearts and in hearts with approximately 250-fold
overexpression of functionally coupled A(1)-adenosine receptors (A(1)ARs). In
wild-type hearts, time to onset of contracture (TOC) was 303 +/- 24 s, with a
peak contracture of 89 +/- 5 mmHg. Diastolic pressure remained elevated at 52 +/-
6 mmHg after reperfusion, and developed pressure recovered to 40 +/- 6% of
preischemia. A(1)AR overexpression markedly prolonged TOC to 517 +/- 84 s,
reduced contracture to 64 +/- 6 mmHg, and improved recovery of diastolic (to 9 +/
4 mmHg) and developed pressure (to 82 +/- 8%). 5-Hydroxydecanoate (5-HD; 100
microM), a mitochondrial K(ATP) blocker, did not alter ischemic contracture in
wild-type hearts, but increased diastolic pressure to 69 +/- 8 mmHg and reduced
developed pressure to 10 +/- 5% during reperfusion. In transgenic hearts, 5-HD
reduced TOC to 348 +/- 18 s, increased postischemic contracture to 53 +/- 4 mmHg,
and reduced recovery of developed pressure to 22 +/- 4%. In summary, these data
are the first to demonstrate that endogenous activation of K(ATP) channels
improves tolerance to ischemia-reperfusion in murine myocardium. This functional
protection occurs without modification of ischemic contracture. The data also
support a role for mitochondrial K(ATP) channel activation in the pronounced
cardioprotection afforded by overexpression of myocardial A(1)ARs.
PMID- 11009457
TI - Validation of a mouse conductance system to determine LV volume: comparison to
echocardiography and crystals.
AB - The application of left ventricular pressure-volume analysis to transgenic mice
to characterize the cardiac phenotype has been problematic due to the small size
of the mouse heart and the rapid heartbeat. Conductance technology has been
miniaturized for the mouse and can solve this problem. However, there has been no
validation of this technique. Accordingly, we performed echocardiography followed
by simultaneous ultrasonic crystals, flow probe, and conductance studies in 18 CD
1 mice. Raw conductance volumes were corrected for an inhomogenous electrical
field (alpha) and parallel conductance (G(pi)) yielding a stroke volume of 14.1
+/- 3.7 microliter/beat, end-diastolic volume of 20.8 +/- 6.5 microliter, and end
systolic volume of 9.0 +/- 5.8 microliter. The mean conductance volumes were no
different from those derived by flow probe and echocardiography but did differ
from ultrasonic crystals. G(pi) was determined to be 14.9 +/- 8.7 microliter.
However, hypertonic saline altered dimension and pressure in the mouse left
ventricle. Although G(pi) can be determined by the hypertonic saline method,
saline altered hemodynamics, questioning its validity in the mouse. Although mean
measures of absolute volume may be similar among different techniques, individual
values did not correlate.
PMID- 11009458
TI - Reduced contractile response to insulin and IGF-I in ventricular myocytes from
genetically obese Zucker rats.
AB - Obesity plays a pivotal role in the pathophysiology of metabolic and
cardiovascular diseases. Resistance to insulin is commonly seen in metabolic
disorders such as obesity and diabetes. Insulin-like growth factor-I (IGF-I)
mimics insulin in many tissues and has been shown to enhance cardiac contractile
function and growth. Because IGF-I resistance often accompanies resistance to
insulin, we sought to determine whether IGF-I-induced myocardial contractile was
elevated and whether heart and kidney size were enlarged in obese compared with
lean rats. The myocyte contraction profile in the obese rats showed a decreased
peak shortening associated with prolonged relengthening and normal shortening
duration, a pattern similar to that observed in diabetes. IGF-I (1-500 ng/ml)
caused a dose-dependent increase in peak shortening in lean but not obese
animals, but it did not alter the duration of shortening and relengthening.
Consistent with contractile data, IGF-I induced a dose-dependent increase in
Ca(2+) transients only in myocytes of lean rats. IGF-I receptor mRNA levels were
significantly reduced in obese rat hearts. These results suggest that the IGF-I
induced cardiac contractile responses are attenuated in the Zucker model of
obesity. The mechanisms underlying this alteration may be related to the
decreased receptor number and/or changes in intracellular Ca(2+) handling in
these animals.
PMID- 11009459
TI - Time course of vasodilatory responses in skeletal muscle arterioles: role in
hyperemia at onset of exercise.
AB - At the onset of dynamic exercise, muscle blood flow increases within 1-2 s. It
has been postulated that local vasodilatory agents produced by the vascular
endothelium or the muscle itself contribute to this response. We hypothesized
that only vasodilators that act directly on the vascular smooth muscle could
produce vasodilation of skeletal muscle arterioles in <2 s. To test this
hypothesis, we determined the time course of the vasodilatory response of
isolated skeletal muscle arterioles to direct application of potassium chloride,
adenosine, acetylcholine, and sodium nitroprusside. Soleus and gastrocnemius
muscles were dissected from the hindlimbs of male Sprague-Dawley rats. First
order arterioles (100-200 microm) were isolated, cannulated on micropipettes, and
pressurized to 60 cmH(2)O in an organ bath. Vasodilatory agents were added
directly to the bath, and diameter responses of the arterioles were recorded in
real time on a videotape recorder. Frame-by-frame analysis of the diameter
responses indicated that none of the vasodilator agents tested produced
significant diameter increases in <4 s in either soleus or gastrocnemius muscle
arterioles. These results indicate that, although these local vasodilators
produce significant vasodilation of skeletal muscle resistance arterioles, these
responses are not rapid enough (within 1-2 s) to contribute to the initiation of
the exercise hyperemic response at the onset of dynamic exercise.
PMID- 11009460
TI - Starling forces that oppose filtration after tissue oncotic pressure is
increased.
AB - We tested the hypothesis that the effective oncotic force that opposes fluid
filtration across the microvessel wall is the local oncotic pressure difference
across the endothelial surface glycocalyx and not the global difference between
the plasma and tissue. In single frog mesenteric microvessels perfused and
superfused with solutions containing 50 mg/ml albumin, the effective oncotic
pressure exerted across the microvessel wall was not significantly different from
that measured when the perfusate alone contained albumin at 50 mg/ml.
Measurements were made during transient and steady-state filtration at capillary
pressures between 10 and 35 cmH(2)O. A cellular-level model of coupled water and
solute flows in the interendothelial cleft showed water flux through small breaks
in the junctional strand limited back diffusion of albumin into the protected
space on the tissue side of the glycocalyx. Thus oncotic forces opposing
filtration are larger than those estimated from blood-to-tissue protein
concentration differences, and transcapillary fluid flux is smaller than
estimated from global differences in oncotic and hydrostatic pressures.
PMID- 11009461
TI - Endocardial activation during ventricular fibrillation in normal and failing
canine hearts.
AB - Because congestive heart failure (CHF) promotes ventricular fibrillation (VF), we
compared VF in seven dogs with CHF induced by combined myocardial infarction and
rapid ventricular pacing to VF in six normal dogs. A noncontact, multielectrode
array balloon catheter provided full-surface real-time left ventricular (LV)
endocardial electrograms and a dynamic color-coded display of endocardial
activation projected onto a three-dimensional model of the LV. Fast Fourier
transform (FFT) analysis of virtual electrograms showed no difference in peak or
centroid frequency in CHF dogs compared with normals. The average number of
simultaneous noncontiguous wavefronts present during VF was higher in normals
(2.4 +/- 1.0 at 10 s of VF) than in CHF dogs (1.3 +/- 1.0, P < 0.005) and
decreased in both over time. The wavefront "turnover" rate, estimated using FFT
of the noncontiguous wavefront data, did not differ between normals and CHF and
did not change over 5 min of VF. Thus the fundamental frequency characteristics
of VF are unaltered by CHF, but dilated abnormal ventricles sustain fewer active
wavefronts than do normal ventricles.
PMID- 11009462
TI - Novel characteristics of a misprocessed mutant HERG channel linked to hereditary
long QT syndrome.
AB - Hereditary long QT syndrome (hLQTS) is a heterogeneous genetic disease
characterized by prolonged QT interval in the electrocardiogram, recurrent
syncope, and sudden cardiac death. Mutations in the cardiac potassium channel
HERG (KCNH2) are the second most common form of hLQTS and reduce the delayed
rectifier K(+) currents, thereby prolonging repolarization. We studied a novel
COOH-terminal missense mutation, HERG R752W, which segregated with the disease in
a family of 101 genotyped individuals. When the mutant cRNA was expressed in
Xenopus oocytes it produced enhanced rather than reduced currents. Simulations
using the Luo-Rudy model predicted minimal shortening rather than prolongation of
the cardiac action potential. Consequently, a normal or shortened QT interval
would be expected in contrast to the long QT observed clinically. This anomaly
was resolved by our observation that the mutant protein was not delivered to the
plasma membrane of mammalian cells but was retained intracellularly. We found
that this trafficking defect was corrected at lower incubation temperatures and
that functional channels were now delivered to the plasma membrane. However,
trafficking could not be restored by chemical chaperones or E-4031, a specific
blocker of HERG channels. Therefore, HERG R752W represents a new class of
trafficking mutants in hLQTS. The occurrence of different classes of misprocessed
channels suggests that a unified therapeutic approach for altering HERG
trafficking will not be possible and that different treatment modalities will
have to be matched to the different classes of trafficking mutants.
PMID- 11009463
TI - Upregulation of neuronal nitric oxide synthase in skeletal muscle by swim
training.
AB - Exercise enhances cardiac output and blood flow to working skeletal muscles but
decreases visceral perfusion. The alterations in nitric oxide synthase (NOS)
activity and/or expression of the cardiopulmonary, skeletal muscle, and visceral
organs induced by swim training are unknown. In sedentary and swim-trained rats
(60 min twice/day for 3-4 wk), we studied the alterations in NOS in different
tissues along with hindquarter vasoreactivity in vivo during rest and mesenteric
vascular bed reactivity in vitro. Hindquarter blood flow and conductance were
reduced by norepinephrine in both groups to a similar degree, whereas N(G)-nitro
L-arginine methyl ester reduced both indexes to a greater extent in swim-trained
rats. Vasodilator responses to ACh, but not bradykinin or S-nitroso-N-acetyl
penicillamine, were increased in swim-trained rats. Ca(2+)-dependent NOS activity
was enhanced in the hindquarter skeletal muscle, lung, aorta, and atria of swim
trained rats together with increased expression of neuronal NOS in the
hindquarter skeletal muscle and endothelial NOS in the cardiopulmonary organs.
Mesenteric arterial bed vasoreactivity was unaltered by swim training.
Physiological adaptations to swim training are characterized by enhanced
hindquarter ACh-induced vasodilation with upregulation of neuronal NOS in
skeletal muscle and endothelial NOS in the lung, atria, and aorta.
PMID- 11009464
TI - Mathematical analysis of canine atrial action potentials: rate, regional factors,
and electrical remodeling.
AB - Dogs have been used extensively to study atrial arrhythmias, but there are no
published mathematical models of the canine atrial action potential (AP). To
obtain insights into the ionic mechanisms governing canine atrial AP properties,
we incorporated formulations of K(+), Na(+), Ca(2+), and Cl(-) currents, based on
measurements in canine atrial myocytes, into a mathematical model of the AP. The
rate-dependent behavior of model APs corresponded to experimental measurements
and pointed to a central role for L-type Ca(2+) current inactivation in rate
adaptation. Incorporating previously described regional ionic current variations
into the model largely reproduced AP forms characteristic of the corresponding
right atrial regions (appendage, pectinate muscle, crista terminalis, and
atrioventricular ring). When ionic alterations induced by tachycardia-dependent
remodeling were incorporated, the model reproduced qualitatively the AP features
constituting the cellular substrate for atrial fibrillation. We conclude that
this ionic model of the canine atrial AP agrees well with experimental
measurements and gives potential insights into mechanisms underlying functionally
important electrophysiological phenomena in canine atrium.
PMID- 11009465
TI - Alterations of endothelium and smooth muscle function in monocrotaline-induced
pulmonary hypertensive arteries.
AB - We examined how monocrotaline (MCT), which impairs the endothelium and causes
pulmonary hypertension, altered the endothelial regulation of pulmonary artery
functions. Rats were given a single injection of MCT (60 mg/kg sc). Pulmonary
arteries were depolarized to -48.3 +/- 2.6 and -39.8 +/- 2.2 mV at 2 and 3 wk
after treatment with MCT, respectively (control arteries -59.9 +/- 1.9 mV). The
basal tone in the resting state was only slightly elevated at 3 wk in endothelium
intact arteries. Removal of the endothelium caused further depolarization in MCT
affected arteries at 2 wk, but not at 3 wk, and greatly elevated the basal tone
at 2 and 3 wk. N(omega)-nitro-L-arginine (200 microM), a nitric oxide synthase
inhibitor, also caused depolarization in endothelium-intact arteries in both
groups and elevated the basal tone of MCT-affected arteries. The relaxant
responses of pulmonary arteries to ACh and A-23187 were depressed at 2 and 3 wk
after MCT treatment. Thus chronic impairment of the endothelium altered the
property of the pulmonary artery leading to depolarization. During the early
stage of depolarization, a rise in the basal tone was offset by nitric oxide
released from the injured endothelium.
PMID- 11009466
TI - Methods for assessing hepatic distending pressure and changes in hepatic
capacitance in pigs.
AB - The equilibrium pressure obtained during simultaneous occlusion of hepatic
vascular inflow and outflow was taken as the reference estimate of hepatic
vascular distending pressure (P(hd)). P(hd) at baseline was 1.1 +/- 0.2 (mean +/-
SE) mmHg higher than hepatic vein pressure (P(hv)) and 0.7 +/- 0.3 mmHg lower
than portal vein pressure (P(pv)). Norepinephrine (NE) infusion increased P(hd)
by 1. 5 +/- 0.5 mmHg and P(pv) by 3.7 +/- 0.6 mmHg but did not significantly
increase P(hv). Hepatic lobar vein pressure (P(hlv)) measured by a micromanometer
tipped 2-Fr catheter closely resembled P(hd) both at baseline and during NE
infusion. Dynamic pressure-volume (PV) curves were constructed from continuous
measurements of P(hv) and hepatic blood volume increases (estimated by
sonomicrometry) during brief occlusions of hepatic vascular outflow and compared
with static PV curves constructed from P(hd) determinations at five different
hepatic volumes. Estimates of hepatic vascular compliance and changes in
unstressed blood volume from the two methods were in close agreement with hepatic
compliance averaging 32 +/- 2 ml. mmHg(-1). kg liver(-1). NE infusion reduced
unstressed blood volume by 110 +/- 38 ml/kg liver but did not alter compliance.
In conclusion, P(hlv) reflects hepatic distending pressure, and the construction
of dynamic PV curves is a fast and valid method for assessing hepatic compliance
and changes in unstressed blood volume.
PMID- 11009467
TI - Angiotensin II acutely attenuates range of arterial baroreflex control of renal
sympathetic nerve activity.
AB - Acutely increasing peripheral angiotensin II (ANG II) reduces the maximum renal
sympathetic nerve activity (RSNA) observed at low mean arterial blood pressures
(MAPs). We postulated that this observation could be explained by the action of
ANG II to acutely increase arterial blood pressure or increase circulating
arginine vasopressin (AVP). Sustained increases in MAP and increases in
circulating AVP have previously been shown to attenuate maximum RSNA at low MAP.
In conscious rabbits pretreated with an AVP V1 receptor antagonist, we compared
the effect of a 5-min intravenous infusion of ANG II (10 and 20 ng x kg(-1) x
min(-1)) on the relationship between MAP and RSNA when the acute pressor action
of ANG II was left unopposed with that when the acute pressor action of ANG II
was opposed by a simultaneous infusion of sodium nitroprusside (SNP). Intravenous
infusion of ANG II resulted in a dose-related attenuation of the maximum RSNA
observed at low MAP. When the acute pressor action of ANG II was prevented by
SNP, maximum RSNA at low MAP was attenuated, similar to that observed when ANG II
acutely increased MAP. In contrast, intravertebral infusion of ANG II attenuated
maximum RSNA at low MAP significantly more than when administered intravenously.
The results of this study suggest that ANG II may act within the central nervous
system to acutely attenuate the maximum RSNA observed at low MAP.
PMID- 11009468
TI - Effects of mammary engorgement and feed withdrawal on microvascular function in
lactating goat mammary glands.
AB - The responses of the mammary microvasculature in lactating goats (n = 8) during
feed withdrawal (18-20 h) and mammary engorgement (26-28 h of milk accumulation)
were compared using an indicator-dilution technique with FITC-albumin and
[(14)C]sucrose as the intravascular and diffusible indicators, respectively. Feed
withdrawal and mammary engorgement caused a 50-60% decrease in mammary arterial
flow and in the permeability-surface area product (PS) values for sucrose. Only
feed withdrawal increased the mean transit time [from 17.3 to 30.0 s, SE of the
difference (SED) = 2.16, P < 0.01] of FITC-albumin, whereas only mammary
engorgement reduced sucrose extraction (0.63 to 0.51, SED = 0.04, P < 0.05).
Mammary engorgement also caused a substantial reduction in the sucrose-accessible
extravascular space from 92 to 44 ml (SED = 15.2, P < 0.01). In a separate
experiment using five goats, milking after mammary engorgement did not
immediately restore arterial flow or sucrose extraction, indicating that the
effect of milk accumulation was not mediated simply via increased intramammary
pressure. In conclusion, feed withdrawal resulted in slower flow in the capillary
bed but apparently no change in capillary recruitment, whereas mammary
engorgement caused capillary derecruitment.
PMID- 11009469
TI - Role of pertussis toxin-sensitive G protein in metabolic vasodilation of coronary
microcirculation.
AB - We have previously demonstrated that pertussis toxin (PTX)-sensitive G protein
(G(PTX)) plays a major role in coronary microvascular vasomotion during
hypoperfusion. We aimed to elucidate the role of G(PTX) during increasing
metabolic demand. In 18 mongrel dogs, coronary arteriolar diameters were measured
by fluorescence microangiography using a floating objective. Myocardial oxygen
consumption (MVO(2)) was increased by rapid left atrial pacing. In six dogs, PTX
(300 ng/ml) was superfused onto the heart surface for 2 h to locally block
G(PTX). In eight dogs, the vehicle (Krebs solution) was superfused in the same
way. Before and after each treatment, the diameters were measured during control
(130 beats/min) and rapid pacing (260 beats/min) in each group. Metabolic
stimulation before and after the vehicle treatment caused 8.6 +/- 1. 8 and 16.1
+/- 3.6% dilation of coronary arterioles <100 microm in diameter (57 +/- 8 microm
at control, n = 10), respectively. PTX treatment clearly abolished the dilation
of arterioles (12.8 +/- 2. 5% before and 0.9 +/- 1.6% after the treatment, P <
0.001 vs. vehicle; 66 +/- 8 microm at control, n = 11) in response to metabolic
stimulation. The increases in MVO(2) and coronary flow velocity were comparable
between the vehicle and PTX groups. In four dogs, 8-phenyltheophylline (10
microM, superfusion for 30 min) did not affect the metabolic dilation of
arterioles (15.3 +/- 2.0% before and 16.4 +/- 3.8% after treatment; 84.3 +/- 11.0
microm at control, n = 8). Thus we conclude that G(PTX) plays a major role in
regulating the coronary microvascular tone during active hyperemia, and adenosine
does not contribute to metabolic vasodilation via G(PTX) activation.
PMID- 11009471
TI - 2,3-butanedione monoxime unmasks Ca(2+)-induced NADH formation and inhibits
electron transport in rat hearts.
AB - We used 2,3-butanedione monoxime (BDM) to suppress work by the perfused rat heart
and to investigate the effects of calcium on NADH production and tissue
energetics. Hearts were perfused with buffer containing BDM and elevated
perfusate calcium to maintain the rates of cardiac work and oxygen consumption at
levels similar to those of control perfused hearts. BDM plus calcium hearts
displayed higher levels of NADH surface fluorescence, indicating calcium
activation of mitochondrial dehydrogenases. These hearts, however, displayed 20%
lower phosphocreatine levels. BDM suppressed the rates of state 3 respiration of
isolated mitochondria. Uncoupled respiration was suppressed to a lesser degree,
and the state 4 respiration rates were not affected. Double-inhibitor experiments
with liver mitochondria using BDM and carboxyatractyloside (CAT) were used to
identify the site of inhibition. BDM at low levels (0-5 mM) suppressed
respiration. In the presence of CAT at levels that inhibit respiration by 60%,
low levels of BDM were without effect. Because these effects were not additive,
BDM does not inhibit adenine nucleotide transport. This was supported by an assay
of adenine nucleotide transport in liver mitochondria. BDM did not inhibit ATP
hydrolysis by submitochondrial particles but strongly suppressed reversed
electron transport from succinate to NAD(+). Oxidation of NADH by
submitochondrial particles was inhibited by BDM but oxidation of succinate was
not. We conclude that BDM inhibits electron transport at site 1.
PMID- 11009470
TI - Relationship of molecular structure to the mechanism of lysophospholipid-induced
smooth muscle cell proliferation.
AB - We previously reported that oxidized low-density lipoprotein and one of its
constituents, lysophosphatidylcholine (lysoPC), caused smooth muscle cell
proliferation that was inhibitable by vitamin E and by a neutralizing antibody
against basic fibroblast growth factor-2 (FGF-2). We now show that the mitogenic
activity of lysolipids is highly dependent on structure. Phospholipids with
palmitoyl fatty acid and phosphocholine induced DNA synthesis optimally. Shorter
and longer fatty acids were significantly less potent, as were phosphoserine and
phosphoethanolamine head groups. Structurally related phospholipids [platelet
activating factor (PAF) and lysoPAF] were also mitogens and acted via an
analogous FGF-2-dependent, vitamin E-inhibitable mechanism. The mechanism of
lysoPC stimulation was distinct from that of another phospholipid mitogen,
lysophosphatidic acid (lysoPA), in that lysoPC stimulation was not pertussis
toxin inhibitable. Furthermore, lysoPA stimulation was not inhibitable by vitamin
E. Despite its distinct cellular pathway for stimulation, lysoPA also ultimately
led to FGF-2 release. Our data show that specific structural attributes of
lysoPC, PAF, and lysoPAF enable these agents to mediate smooth muscle cell
release of FGF-2, which in turn stimulates proliferation.
PMID- 11009472
TI - Mitochondrial NAD(P)H, ADP, oxidative phosphorylation, and contraction in
isolated heart cells.
AB - To examine the relationship between mitochondrial NADH (NADH(m)) and cardiac work
output, NADH(m) and the amplitude and frequency of the contractile response of
electrically paced rat heart cells were measured at 25 degrees C. With 5.4 mM
glucose plus 2 mM beta-hydroxybutyrate, NADH(m) was reversibly decreased by 23%,
and the amplitude of contraction was reversibly decreased by 27% during 4-Hz
pacing. With glucose plus 2 mM pyruvate or with 10 mM 2-deoxy-D-glucose, NADH(m)
was maintained during rapid pacing, and the contractile amplitude remained high.
Phosphocreatine levels decreased with 2-deoxy-D-glucose administration but not
with rapid pacing. Respiration increased to meet the increased ATP demand at 30
degrees C. The data suggest that 1) when NADH(m) is decreased during rapid pacing
with defined substrates, the amplitude of contraction is decreased; 2) the
amplitude of contraction during electrical pacing does not change with rate of
pacing when both the ATP and NADH(m) levels are continuously replenished; and 3)
the replenishment of NADH(m) during pacing with physiological substrates may be
rate-limited by substrate supply to mitochondrial dehydrogenases. During
activation of mitochondrial dehydrogenases, or a significant increase in free ADP
induced by 2-deoxy-D-glucose, this rate limitation is bypassed or overcome.
PMID- 11009477
TI - Prior exercise training increases collateral-dependent blood flow in rats after
acute femoral artery occlusion.
AB - We evaluated whether prior training would improve collateral blood flow (BF) to
the calf muscles after acute-onset occlusion of the femoral artery. Exercise
training was performed in the absence of any vascular occlusion. Adult male
Sprague-Dawley rats ( approximately 325 g) were kept sedentary (n = 14), limited
to cage activity, or exercise trained (n = 14) for 6 wk by treadmill running.
Early in the day of measurement, animals were surgically prepared for BF
determination, and the femoral arteries were occluded bilaterally. Four to five
hours later, collateral BF was determined twice during treadmill running with the
use of (141)Ce and (85)Sr microspheres: first, at a demanding speed and, second,
after a brief rest and at a higher speed. The absence of any further increase in
BF at the higher speed indicated that maximal collateral BF was measured. Prior
training increased calf muscle BF by approximately 70% compared with sedentary
animals; however, absolute BF remained below values previously observed in
animals with a well-developed collateral vascular tree. Thus prior training
appeared to optimize the use of the existing collateral circuit. This implies
that altered vasoresponsiveness induced in normal nonoccluded vessels with
exercise training serves to improve collateral BF to the periphery.
PMID- 11009475
TI - Dynamics of action potential head-tail interaction during reentry in cardiac
tissue: ionic mechanisms.
AB - In a sufficiently short reentry pathway, the excitation wave front (head)
propagates into tissue that is partially refractory (tail) from the previous
action potential (AP). We incorporate a detailed mathematical model of the
ventricular myocyte into a one-dimensional closed pathway to investigate the
effects of head-tail interaction and ion accumulation on the dynamics of reentry.
The results were the following: 1) a high degree of head-tail interaction
produces oscillations in several AP properties; 2) Ca(2+)-transient oscillations
are in phase with AP duration oscillations and are often of greater magnitude; 3)
as the wave front propagates around the pathway, AP properties undergo periodic
spatial oscillations that produce complicated temporal oscillations at a single
site; 4) depending on the degree of head-tail interaction, intracellular [Na(+)]
accumulation during reentry either stabilizes or destabilizes reentry; and 5)
elevated extracellular [K(+)] destabilizes reentry by prolonging the tail of
postrepolarization refractoriness.
PMID- 11009473
TI - Flumazenil preconditions cardiomyocytes via oxygen radicals and K(ATP) channels.
AB - We determined whether flumazenil mimics ischemic preconditioning in chick
cardiomyocytes and examined the role of intracellular reactive oxygen species
(ROS) and ATP-dependent potassium (K(ATP)) channels in mediating the effect.
Chick ventricular myocytes were perfused with a balanced salt solution in a flow
through chamber. Cell viability was quantified using propidium iodide, and ROS
generation was assessed using the reduced form of 2',7'-dichlorofluorescin
(DCFH). Cells were exposed to 1 h of simulated ischemia and 3 h of reoxygenation.
Preconditioning was initiated with 10 min of ischemia followed by 10 min of
reoxygenation. Alternatively, flumazenil was added to the perfusate for 10 min
and removed 10 min before the start of ischemia. Flumazenil (1 and 10 microM) and
preconditioning reduced cell death [54 +/- 5%, n = 3; 26 +/- 4%, n = 6 (P <
0.05); and 20 +/- 2%, n = 6 (P < 0.05), respectively, vs. 57 +/- 7%, n = 10, in
controls] and increased DCFH oxidation (an index of ROS production) [0.35 +/-
0.11, n = 3; 2.64 +/- 0.69, n = 8 (P < 0.05); and 2.46 +/- 0.52, n = 6 (P <
0.05), respectively, vs. 0.26 +/- 0.05, n = 9, in controls]. Protection and
increased ROS signals with flumazenil (10 microM) were abolished with the thiol
reductant N-(2-mercaptopropionyl)-glycine (2-MPG, 800 microM), an antioxidant
(cell death: 2-MPG + flumazenil, 55 +/- 12%, n = 6; ROS signals: 2-MPG +
flumazenil, 0.11 +/- 0.19, n = 6). Treatment with 5-hydroxydecanoate (1 mM), a
selective mitochondrial K(ATP) channel antagonist, abolished its protection.
These results demonstrate that flumazenil mimics preconditioning to reduce cell
death in myocytes. ROS signals with the resultant mitochondrial K(ATP) channel
activation are important components of the intracellular signaling pathway of
flumazenil.
PMID- 11009474
TI - Protein washdown as a defense mechanism against myocardial edema.
AB - Myocardial edema occurs in many pathological conditions. We hypothesized that
protein washdown at the myocardial microvascular exchange barrier would change
the distribution of interstitial proteins from large to small molecules and
diminish the effect of washdown on the colloid osmotic pressure (COP) of
interstitial fluid and lymph. Dogs were instrumented with coronary sinus balloon
tipped catheters and myocardial lymphatic cannulas to manipulate myocardial lymph
flow and to collect lymph. Myocardial venous pressure was elevated by balloon
inflation to increase transmicrovascular fluid flux and myocardial lymph flow.
COP of lymph was measured directly and was also calculated from protein
concentration. Decreases occurred in both protein concentration and COP of lymph.
The proportion of lymph protein accounted for by albumin increased significantly,
whereas that accounted for by beta-lipoprotein decreased significantly. The
change in the calculated plasma-to-lymph COP gradient was significantly greater
than the change in the measured COP gradient. We conclude that the change in the
distribution of interstitial fluid protein species decreases the effect of
protein washdown on interstitial fluid COP and limits its effectiveness as a
defense mechanism against myocardial edema formation.
PMID- 11009478
TI - Effect of milrinone on left ventricular relaxation and Ca(2+) uptake function of
cardiac sarcoplasmic reticulum.
AB - Milrinone, a phosphodiesterase 3 (PDE3) inhibitor, is known to enhance left
ventricular (LV) contractility by an inhibition of the breakdown of cAMP through
the mechanism inhibiting PDE3. However, it is unclear whether milrinone also
exerts positive lusitropy, like dobutamine. Here, we assessed the effects of
milrinone on in vivo LV relaxation, as well as the Ca(2+)-ATPase activity and the
Ca(2+) uptake function of the cardiac sarcoplasmic reticulum (SR), compared with
the effect of dobutamine on those functions. After dobutamine (3 microg x kg(-1)
x min(-1)) was administered, the peak value of the first derivative of LV
pressure (+dP/dt) increased by 46%, whereas the time constant (tau) of LV
pressure decay decreased by 6.9%, respectively. After milrinone (10 microg/kg)
was administered, the peak +dP/dt increased to a similar extent as dobutamine
(46%), whereas tau decreased much more than dobutamine (19.9%; P < 0.05). In LV
crude homogenate, the thapsigargin-sensitive, Ca(2+)-ATPase activity-cAMP
relationships was significantly less increased by milrinone compared with
dobutamine (P < 0.05), indicating the higher sensitivity of the SR Ca(2+)-ATPase
activity on cAMP by milrinone than by dobutamine. In the SR vesicles purified
from LV muscles, the addition of cAMP increased the SR Ca(2+) uptake in a dose
dependent fashion, and the PDE3 inhibitors (milrinone and cGMP) significantly
augmented this response (P < 0.05). Hence, milrinone substantially improved LV
relaxation in association with an acceleration of the SR Ca(2+)-ATPase activity
and the SR Ca(2+) uptake. This acceleration might be due to an inhibition of the
membrane-bound PDE3 in the SR, leading to a local elevation of cAMP.
PMID- 11009476
TI - Interactions of hemoglobin with hydrogen peroxide alters thiol levels and course
of endothelial cell death.
AB - We investigated cellular injury and death induced by ultrapure human Hb (HbA(0))
and its diaspirin cross-linked derivative DBBF-Hb in normal and glutathione (GSH)
depleted bovine aortic endothelial cells subjected to hydrogen peroxide
(H(2)O(2)). HbA(0) underwent extensive degradation and heme loss, whereas DBBF-Hb
persisted longer in its ferryl (Fe(4+)) form. The formation of ferryl HbA(0) or
ferryl DBBF-Hb was associated with a significant decrease in endothelial cell GSH
compared with the addition of H(2)O(2) or Hbs alone. This effect was inhibited by
catalase, but not by superoxide dismutase or deferoxamine mesylate. The presence
of HbA(0) and DBBF-Hb reduced H(2)O(2)-induced apoptosis, as measured by cell
morphology, annexin V binding assay, and caspase inhibition, consistent with the
ability to consume H(2)O(2) in an enzyme-like fashion. However, the pattern of
cell death and injury produced by HbA(0) and DBBF-Hb appeared to be distinctly
different among proteins as well as among cells with and without GSH. These
findings may have important implications for the use of cell-free Hb as oxygen
therapeutics in patients with coexisting pathologies who may lack antioxidant
protective mechanisms.
PMID- 11009479
TI - Vasodilator mechanisms in the coronary circulation of endothelial nitric oxide
synthase-deficient mice.
AB - Previous studies have demonstrated that responses to endothelium-dependent
vasodilators are absent in the aortas from mice deficient in expression of
endothelial nitric oxide synthase (eNOS -/- mice), whereas responses in the
cerebral microcirculation are preserved. We tested the hypothesis that in the
absence of eNOS, other vasodilator pathways compensate to preserve endothelium
dependent relaxation in the coronary circulation. Diameters of isolated,
pressurized coronary arteries from eNOS -/-, eNOS heterozygous (+/-), and wild
type mice (eNOS +/+ and C57BL/6J) were measured by video microscopy. ACh (an
endothelium-dependent agonist) produced vasodilation in wild-type mice. This
response was normal in eNOS +/- mice and was largely preserved in eNOS -/- mice.
Responses to nitroprusside were also similar in arteries from eNOS +/+, eNOS +/-,
and eNOS -/- mice. Dilation to ACh was inhibited by N(G)-nitro-L-arginine, an
inhibitor of NOS in control and eNOS -/- mice. In contrast,
trifluoromethylphenylimidazole, an inhibitor of neuronal NOS (nNOS), decreased
ACh-induced dilation in arteries from eNOS-deficient mice but had no effect on
responses in wild-type mice. Indomethacin, an inhibitor of cyclooxygenase,
decreased vasodilation to ACh in eNOS-deficient, but not wild-type, mice. Thus,
in the absence of eNOS, dilation of coronary arteries to ACh is preserved by
other vasodilator mechanisms.
PMID- 11009480
TI - Time and dose effect of transdermal nicotine on endothelial function.
AB - Nicotine patches are available as an over-the-counter medication for aid in
smoking cessation. This study was designed to determine how nicotine patch
therapy over time and dose ranges used in smoking cessation programs in humans
affects endothelium-dependent relaxations. Dogs were treated with nicotine
patches (11, 22, or 44 mg/day) for 2 and 5 wk. Circulating nicotine and oxidized
products of nitric oxide (NOx) were measured. Coronary arteries were prepared for
measurement of isometric force and aortic endothelial cells were prepared for
measurement of mRNA or NO synthase (NOS) activity. Circulating nicotine increased
with increasing concentrations of nicotine patches. After 5 wk of treatment with
22 mg/day patches, circulating NOx was reduced but NOS activity was increased.
NOS mRNA was similar among groups. Only after 5 wk of treatment with 22 mg/day
patches were endothelium-dependent relaxations reduced to alpha(2)-adrenergic
agonists, ADP, and the calcium ionophore A-23187. These results suggest a time
and biphasic dose effect of nicotine treatment on endothelium-dependent responses
that may be related to bioavailability of NO. This complex relationship of
duration and dose of nicotine treatment may explain, in part, discrepancies in
effects of nicotine on endothelium-dependent responses.
PMID- 11009481
TI - Diaspirin cross-linked Hb and norepinephrine prevent the sepsis-induced increase
in critical O(2) delivery.
AB - We hypothesized that support of arterial perfusion pressure with diaspirin cross
linked Hb (DCLHb) would prevent the sepsis-induced attenuation in the systemic
O(2) delivery-O(2) uptake relationship. Awake septic rats were treated with a
chronic infusion of DCLHb or a reference treatment [norepinephrine (NE)] to
increase mean arterial pressure by 10-20% over 18 h. Septic and sham control
groups received normal saline. Isovolemic hemodilution to create anemic hypoxia
was then performed in a metabolic box during continuous measurement of systemic
O(2) uptake. O(2) delivery was calculated from hemodynamic variables, and the
critical point of O(2) delivery (DO(2 crit)) was determined using piecewise
regression analysis of the O(2) delivery-O(2) uptake relationship. Sepsis
increased DO(2 crit) from 4.99 +/- 0.17 to 6.69 +/- 0.42 ml x min(-1) x 100 g(-1)
(P < 0.01), while O(2) extraction capacity was decreased (P < 0.05). DCLHb and NE
infusion prevented the sepsis-induced increase in DO(2 crit) [4.56 +/- 0.42 ml x
min(-1) x 100 g(-1) (P < 0.01) and 5.04 +/- 0.56 ml x min(-1) x 100 g(-1) (P <
0.05), respectively]. This was explained by a 59% increase in O(2) extraction
capacity in the DCLHb group compared with septic controls (P < 0.05), whereas NE
treatment decreased systemic O(2) uptake in anemic hypoxia (1.51 +/- 0.08 vs.
1.87 +/- 0.1 ml x min(-1) x 100 g(-1) in septic controls, P < 0.05). We conclude
that DCLHb ameliorated O(2) extraction capacity in the septic microcirculation,
whereas NE decreased the metabolic demands of the tissues.
PMID- 11009482
TI - Cardiovascular and neuroendocrine responses to water immersion in compensated
heart failure.
AB - The hypothesis was tested that cardiovascular and neuroendocrine (norepinephrine,
renin, and vasopressin) responses to central blood volume expansion are blunted
in compensated heart failure (HF). Nine HF patients [New York Heart Association
class II-III, ejection fraction = 0.28 +/- 0.02 (SE)] and 10 age-matched controls
(ejection fraction = 0.68 +/- 0.03) underwent 30 min of thermoneutral (34.7 +/-
0.02 degrees C) water immersion (WI) to the xiphoid process. WI increased (P <
0.05) central venous pressure by 3.7 +/- 0.6 and 3.2 +/- 0.4 mmHg and stroke
volume index by 12.2 +/- 2.1 and 7.2 +/- 2.1 ml. beat(-1). m(-2) in controls and
HF patients, respectively. During WI, systemic vascular resistance decreased (P <
0.05) similarly by 365 +/- 66 and 582 +/- 227 dyn. s. cm(-5) in controls and HF
patients, respectively. Forearm subcutaneous vascular resistance decreased by 19
+/- 7% (P < 0.05) in controls but did not change in HF patients. Heart rate
decreased less during WI in HF patients, whereas release of norepinephrine,
renin, and vasopressin was suppressed similarly in the two groups. We suggest
that reflex control of forearm vascular beds and heart rate is blunted in
compensated HF but that baroreflex-mediated systemic vasodilatation and
neuroendocrine responses to central blood volume expansion are preserved.
PMID- 11009483
TI - Cardioprotection with kappa-opioid receptor stimulation is associated with a
slowing of cross-bridge cycling.
AB - Opioid and alpha-adrenergic receptor activation protect the heart from ischemic
damage. One possible intracellular mechanism to explain this is that an
improvement in ATP availability contributes to cardioprotection. We tested this
hypothesis by correlating postischemic left ventricular developed pressure (LVDP)
and myofibrillar Ca(2+)-dependent actomyosin Mg(2+)-ATPase from isolated rat
hearts treated with the kappa-opioid receptor agonist U-50488H (1 microM) or the
alpha-adrenergic receptor agonist phenylephrine (10 microM) + propranolol (3
microM). Preischemic treatment with U-50488H or phenylephrine + propranolol
improved postischemic LVDP recovery by 25-30% over control hearts. Ca(2+)
dependent actomyosin Mg(2+)-ATPase was found to be 20% lower in both U-50488H-
and phenylephrine + propranolol-treated hearts compared with control hearts. The
kappa-opioid receptor antagonist nor-binaltorphimine (1 microM) abolished the
effects of U-50488H on postischemic LVDP and actomyosin Mg(2+)-ATPase activity.
Reduced actomyosin ATP utilization was also suggested in single ventricular
myocytes treated with either U-50488H or the protein kinase C activator, phorbol
12-myristate 13-acetate (PMA), because U-50488H and PMA lowered maximum velocity
of unloaded shortening by 15-25% in myocytes. U-50488H and phenylephrine +
propranolol treatment both resulted in increased phosphorylation of troponin I
and C protein. These findings are consistent with the hypothesis that kappa
opioid and alpha-adrenergic receptors decrease actin-myosin cycling rate, leading
to a conservation of ATP and cardioprotection during ischemia.
PMID- 11009484
TI - Plasma viscosity and cerebral blood flow.
AB - We hypothesized that the response of cerebral blood flow (CBF) to changing
viscosity would be dependent on "baseline" CBF, with a greater influence of
viscosity during high-flow conditions. Plasma viscosity was adjusted to 1.0 or
3.0 cP in rats by exchange transfusion with red blood cells diluted in lactated
Ringer solution or with dextran. Cortical CBF was measured by H(2) clearance. Two
groups of animals remained normoxic and normocarbic and served as controls. Other
groups were made anemic, hypercapnic, or hypoxic to increase CBF. Under baseline
conditions before intervention, CBF did not differ between groups and averaged
49.4 +/- 10.2 ml. 100 g(-1). min(-1) (+/-SD). In control animals, changing plasma
viscosity to 1. 0 or 3.0 cP resulted in CBF of 55.9 +/- 8.6 and 42.5 +/- 12.7 ml.
100 g(-1). min(-1), respectively (not significant). During hemodilution,
hypercapnia, and hypoxia with a plasma viscosity of 1. 0 cP, CBF varied from 98
to 115 ml. 100 g(-1). min(-1). When plasma viscosity was 3.0 cP during
hemodilution, hypercapnia, and hypoxia, CBF ranged from 56 to 58 ml. 100 g(-1).
min(-1) and was significantly reduced in each case (P < 0.05). These results
support the hypothesis that viscosity has a greater role in regulation of CBF
when CBF is increased. In addition, because CBF more closely followed changes in
plasma viscosity (rather than whole blood viscosity), we believe that plasma
viscosity may be the more important factor in controlling CBF.
PMID- 11009485
TI - Carotid baroreflex responsiveness in heat-stressed humans.
AB - The effects of whole body heating on human baroreflex function are relatively
unknown. The purpose of this project was to identify whether whole body heating
reduces the maximal slope of the carotid baroreflex. In 12 subjects, carotid
vasomotor and carotid-cardiac baroreflex responsiveness were assessed in
normothermia and during whole body heating. Whole body heating increased
sublingual temperature (from 36.4 +/- 0.1 to 37.4 +/- 0.1 degrees C, P < 0.01)
and increased heart rate (from 59 +/- 3 to 83 +/- 3 beats/min, P < 0. 01),
whereas mean arterial blood pressure (MAP) was slightly decreased (from 88 +/- 2
to 83 +/- 2 mmHg, P < 0.01). Carotid-vasomotor and carotid-cardiac responsiveness
were assessed by identifying the maximal gain of MAP and heart rate to R wave
triggered changes in carotid sinus transmural pressure. Whole body heating
significantly decreased the responsiveness of the carotid-vasomotor baroreflex
(from -0.20 +/- 0.02 to -0.13 +/- 0.02 mmHg/mmHg, P < 0.01) without altering the
responsiveness of the carotid-cardiac baroreflex (from -0.40 +/- 0.05 to -0.36 +/
0.02 beats x min(-1) x mmHg(-1), P = 0.21). Carotid-vasomotor and carotid
cardiac baroreflex curves were shifted downward and upward, respectively, to
accommodate the decrease in blood pressure and increase in heart rate that
accompanied the heat stress. Moreover, the operating point of the carotid-cardiac
baroreflex was shifted closer to threshold (P = 0.02) by the heat stress. Reduced
carotid-vasomotor baroreflex responsiveness, coupled with a reduction in the
functional reserve for the carotid baroreflex to increase heart rate during a
hypotensive challenge, may contribute to increased susceptibility to orthostatic
intolerance during a heat stress.
PMID- 11009486
TI - Biphasic effects of hyposmotic challenge on excitation-contraction coupling in
rat ventricular myocytes.
AB - The effects of short (1 min) and long (7-10 min) exposure to hyposmotic solution
on excitation-contraction coupling in rat ventricular myocytes were studied.
After short exposure, the action potential duration at 90% repolarization
(APD(90)), the intracellular Ca(2+) concentration ([Ca(2+)](i)) transient
amplitude, and contraction increased, whereas the L-type Ca(2+) current (I(Ca,
L)) amplitude decreased. Fractional sarcoplasmic reticulum (SR) Ca(2+) release
increased but SR Ca(2+) load did not. After a long exposure, I(Ca,L), APD(90),
[Ca(2+)](i) transient amplitude, and contraction decreased. The abbreviation of
APD(90) was partially reversed by 50 microM DIDS, which is consistent with the
participation of Cl(-) current activated by swelling. After 10-min exposure to
hyposmotic solution in cells labeled with di-8-aminonaphthylethenylpyridinium, t
tubule patterning remained intact, suggesting the loss of de-t-tubulation was not
responsible for the fall in I(Ca,L). After long exposure, Ca(2+) load of the SR
was not increased, and swelling had no effect on the site-specific
phosphorylation of phospholamban, but fractional SR Ca(2+) release was depressed.
The initial positive inotropic response to hyposmotic challenge may be accounted
for by enhanced coupling between Ca(2+) entry and release. The negative inotropic
effect of prolonged exposure can be accounted for by shortening of the action
potential duration and a fall in the I(Ca,L) amplitude.
PMID- 11009487
TI - Na(+)-K(+)-ATPase alpha(2)-isoform expression in guinea pig hearts during
transition from compensation to decompensation.
AB - Disturbance in ionic gradient across sarcolemma may lead to arrhythmias. Because
Na(+)-K(+)-ATPase regulates intracellular Na(+) and K(+) concentrations, and
therefore intracellular Ca(2+) concentration homeostasis, our aim was to
determine whether changes in the Na(+)-K(+)-ATPase alpha-isoforms in guinea pigs
during transition from compensated (CLVH) to decompensated left ventricular
hypertrophy (DLVH) were concomitant with arrhythmias. After 12- and 20-mo aortic
stenosis, CLVH and DLVH were characterized by increased mean arterial pressure
(30% and 52.7%, respectively). DLVH differed from CLVH by significantly increased
end-diastolic pressure (34%), decreased sarco(endo)plasmic reticulum Ca(2+)
ATPase (-75%), and increased Na(+)/Ca(2+) exchanger (25%) mRNA levels and by the
occurrence of ventricular arrhythmias. The alpha-isoform (mRNA and protein
levels) was significantly lower in DLVH (2.2 +/- 0.2- and 1. 4 +/- 0.15-fold,
respectively, vs. control) than in CLVH (3.5 +/- 0. 4- and 2.2 +/- 0.13-fold,
respectively) and was present in sarcolemma and T tubules. Changes in the levels
of alpha(1)- and alpha(3)-isoform in CLVH and DLVH appear physiologically
irrelevant. We suggest that the increased level of alpha(2)-isoform in CLVH may
participate in compensation, whereas its relative decrease in DLVH may enhance
decompensation and arrhythmias.
PMID- 11009488
TI - cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors:
potential role for nitrosylation.
AB - Nitric oxide (NO) has concentration-dependent biphasic myocardial contractile
effects. We tested the hypothesis, in isolated rat hearts, that NO
cardiostimulation is primarily non-cGMP dependent. Infusion of 3
morpholinosydnonimine (SIN-1, 10(-5) M), which may participate in S-nitrosylation
(S-NO) via peroxynitrite formation, increased the rate of left ventricular
pressure rise (+dP/dt; 19 +/- 4%, P < 0.001, n = 11) without increasing effluent
cGMP or cAMP. Superoxide dismutase (SOD; 150 U/ml) blocked SIN-1
cardiostimulation and led to cGMP elaboration. Sodium nitroprusside (10(-10)-10(
7) M), an iron nitrosyl compound, did not augment +dP/dt but increased cGMP
approximately eightfold (P < 0.001), whereas diethylamine/NO (DEA/NO; 10(-7) M),
a spontaneous NO. donor, increased +dP/dt (5 +/- 2%, P < 0.05, n = 6) without
augmenting cGMP. SIN-1 and DEA/NO +dP/dt increase persisted despite guanylyl
cyclase inhibition with 1H-(1,2,4)oxadiazolo-(4,3,-a)quinoxalin-1-one (10(-5) M,
P < 0.05 for both donors), suggesting a cGMP-independent mechanism. Glutathione
(5 x 10(-4) M, n = 15) prevented SIN-1 cardiostimulation, suggesting S-NO
formation. SIN-1 also produced SOD-inhibitable cardiostimulation in vivo in mice.
Thus peroxynitrite and NO donors can stimulate myocardial contractility
independently of guanylyl cyclase activation, suggesting a role for S-NO
reactions in NO/peroxynitrite-positive inotropic effects in intact hearts.
PMID- 11009489
TI - Cardiac synthesis, processing, and coronary release of enkephalin-related
peptides.
AB - Although preproenkephalin mRNA is abundant in the heart, the myocardial synthesis
and processing of proenkephalin is largely undefined. Isolated working rat hearts
were perfused to determine the rate of myocardial proenkephalin synthesis, its
processing into enkephalin-containing peptides, their subsequent release into the
coronary arteries, and the influence of prior sympathectomy. Enkephalin
containing peptides were separated by gel filtration and quantified with antisera
for specific COOH-terminal sequences. Proenkephalin, peptide B, and
[Met(5)]enkephalin-Arg(6)-Phe(7) (MEAP) comprised 95% of the extracted myocardial
enkephalins (35 pmol/g). Newly synthesized enkephalins, estimated during a 1-h
perfusion with [(14)C]phenylalanine (4 pmol x h(-1) x g wet wt(-1)), were rapidly
cleared from the heart during a second isotope-free hour. Despite a steady
release of enkephalins into the coronary effluent (4 pmol x h(-1) x g wet wt(
1)), enkephalin replacement apparently exceeded its release, and tissue
enkephalins actually accumulated during hour 2. In contrast to the tissue,
methionine-enkephalin accounted for more than half of the released enkephalin.
Chemical sympathectomy produced an increase in total enkephalin content similar
to that observed after 2-h control perfusion. This observation suggested that the
normal turnover of myocardial enkephalin may depend in part on continued
sympathetic influences.
PMID- 11009490
TI - Effect of aerobic and resistance exercise training on vascular function in heart
failure.
AB - Exercise training of a muscle group improves local vascular function in subjects
with chronic heart failure (CHF). We studied forearm resistance vessel function
in 12 patients with CHF in response to an 8-wk exercise program, which
specifically excluded forearm exercise, using a crossover design. Forearm blood
flow (FBF) was measured using strain-gauge plethysmography. Responses to three
dose levels of intra-arterial acetylcholine were significantly augmented after
exercise training when analyzed in terms of absolute flows (7.0 +/- 1.8 to 10.9
+/- 2.1 ml x 100 ml(-1) x min(-1) for the highest dose, P < 0.05 by ANOVA),
forearm vascular resistance (21.5 +/- 5.0 to 15.3 +/- 3.9 ml x 100 ml forearm(-1)
x min(-1), P < 0.01), or FBF ratios (P < 0.01, ANOVA). FBF ratio responses to
sodium nitroprusside were also significantly increased after training (P < 0.05,
ANOVA). Reactive hyperemic flow significantly increased in both upper limbs after
training (27.9 +/- 2.7 to 33.5 +/- 3.1 ml x 100 ml(-1) x min(-1), infused limb; P
< 0.05 by paired t-test). Exercise training improves endothelium-dependent and
independent vascular function and peak vasodilator capacity in patients with CHF.
These effects on the vasculature are generalized, as they were evident in a
vascular bed not directly involved in the exercise stimulus.
PMID- 11009492
TI - Echocardiographic and invasive measurements of pulmonary artery pressure
correlate closely at high altitude.
AB - Exaggerated hypoxia-induced pulmonary hypertension is a hallmark of high-altitude
pulmonary edema (HAPE) and plays a major role in its pathogenesis. Many studies
of HAPE have estimated systolic pulmonary arterial pressure (SPAP) with Doppler
echocardiography. Whereas at low altitude, Doppler echocardiographic estimation
of SPAP correlates closely with its invasive measurement, no such evidence exists
for estimations obtained at high altitude, where alterations of blood viscosity
may invalidate the simplified Bernoulli equation. We measured SPAP by Doppler
echocardiography and invasively in 14 mountaineers prone to HAPE and in 14
mountaineers resistant to this condition at 4,559 m. Mountaineers prone to HAPE
had more pronounced pulmonary hypertension (57 +/- 12 and 58 +/- 10 mmHg for
noninvasive and invasive determination, respectively; means +/- SD) than subjects
resistant to HAPE (37 +/- 8 and 37 +/- 6 mmHg, respectively), and the values
measured in the two groups as a whole covered a wide range of pulmonary arterial
pressures (30-83 mmHg). Spearman test showed a highly significant correlation (r
= 0.89, P < 0.0001) between estimated and invasively measured SPAP values. The
mean difference between invasively measured and Doppler-estimated SPAP was 0.5 +/
8 mmHg. At high altitude, estimation of SPAP by Doppler echocardiography is an
accurate and reproducible method that correlates closely with its invasive
measurement.
PMID- 11009491
TI - Evidence for nitroxidergic innervation in monkey ophthalmic arteries in vivo and
in vitro.
AB - In anesthetized monkeys, electrical stimulation (ES) of the pterygopalatine or
geniculate ganglion dilated the ipsilateral ophthalmic artery (OA). The induced
vasodilatation was unaffected by phentolamine but potentiated by atropine.
Intravenous N(G)-nitro-L-arginine (L-NNA) abolished the response, which was
restored by L-arginine. Hexamethonium-abolished vasodilator responses induced
solely by geniculate ganglionic stimulation. The L-NNA constricted OA; L-arginine
reversed the effect. Destruction of the pterygopalatine ganglion constricted the
ipsilateral artery. Helical strips of OA isolated under deep anesthesia from
monkeys, denuded of endothelium, responded to transmural ES with relaxations,
which were abolished by tetrodotoxin and L-NNA but were potentiated by atropine.
It is concluded that neurogenic vasodilatation of monkey OA is mediated by nerve
derived nitric oxide (NO), and the nerve is originated from the ipsilateral
pterygopalatine ganglion that is innervated by cholinergic neurons from the brain
stem via the geniculate ganglion. The OA appears to be dilated by mediation of NO
continuously liberated from nerves that receive tonic discharges from the
vasomotor center. Acetylcholine liberated from postganglionic cholinergic nerves
would impair the release of neurogenic NO.
PMID- 11009493
TI - Differential effects of L-NAME on rat venular hydraulic conductivity.
AB - The role of nitric oxide (NO) in microvascular permeability remains unclear
because both increases and decreases in permeability by NO synthase (NOS)
inhibitors have been reported. We sought to determine whether blood-borne
constituents modify venular permeability responses to the NOS inhibitor N(G)
nitro-L-arginine methyl ester (L-NAME). We assessed hydraulic conductivity (L(p))
of pipette-perfused rat mesenteric venules before and after exposure to 10(-4) M
L-NAME. In the absence of blood-borne constituents, L-NAME reduced L(p) by nearly
50% (from a median of 2.4 x 10(-7) cm x s(-1) x cmH(2)O(-1), n = 17, P < 0.001).
The reduction in L(p) by L-NAME was inhibited by a 10-fold molar excess of L
arginine but not D-arginine (n = 6). In a separate group of venules, blood flow
was allowed to resume during exposure to L-NAME. In vessels perfused by blood
during L-NAME exposure, L(p) increased by 78% (from 1.4 x 10(-7) cm x s(-1) x
cmH(2)O(-1), n = 10, P < 0.01). N(G)-nitro-D-arginine methyl ester did not affect
L(p) in either of the two groups. These data imply that NO has direct vascular
effects on permeability that are opposed by secondary changes in permeability
mediated by blood-borne constituents.
PMID- 11009494
TI - Voltage-independent changes in L-type Ca(2+) current uncoupled from SR Ca(2+)
release in cardiac myocytes.
AB - To determine the effect of voltage-independent alterations of L-type Ca(2+)
current (I(Ca)) on the sarcoplasmic reticular (SR) Ca(2+) release in cardiac
myocytes, we measured I(Ca) and cytosolic Ca(2+) transients (Ca(i)(2+);
intracellular Ca(2+) concentration) in voltage-clamped rat ventricular myocytes
during 1) an abrupt increase of extracellular [Ca(2+)] (Ca(o)(2+)) or 2)
application of 1 microM FPL-64176, a Ca(2+) channel agonist, to selectively alter
I(Ca) in the absence of changes in SR Ca(2+) loading. On the first depolarization
in higher Ca(o)(2+), peak I(Ca) was increased by 46 +/- 6% (P < 0.001), but the
increases in the maximal rate of rise of Ca(i)(2+) (dCa(i)(2+)/dt(max), where t
is time; an index of SR Ca(2+) release flux) and the Ca(i)(2+) transient
amplitude were not significant. Rapid exposure to FPL-64176 greatly slowed
inactivation of I(Ca), increasing its time integral by 117 +/- 8% (P < 0.001)
without significantly increasing peak I(Ca), dCa(i)(2+)/dt(max), or amplitude of
the corresponding Ca(i)(2+) transient. Prolongation of exposure to higher
Ca(o)(2+) or FPL-64176 did not further increase peak I(Ca) but greatly increased
dCa(i)(2+)/dt(max), Ca(i)(2+) transient amplitude, and the gain of Ca(2+) release
(dCa(i)(2+)/dt(max)/I(Ca)), evidently due to augmentation of the SR Ca(2+)
loading. Also, the time to peak dCa(i)(2+)/dt(max) was significantly increased in
the continuous presence of higher Ca(o)(2+) (by 37 +/- 5%, P < 0.001) or FPL
64176 (by 63 +/- 5%, P < 0.002). Our experiments provide the first evidence of a
marked disparity between an increased peak I(Ca) and the corresponding SR Ca(2+)
release. We attribute this to saturation of the SR Ca(2+) release flux as
predicted by local control theory. Prolongation of the SR Ca(2+) release flux,
caused by combined actions of a larger I(Ca) and maximally augmented SR Ca(2+)
loading, might reflect additional Ca(2+) release from corbular SR.
PMID- 11009495
TI - Strengthening governance for global health research.
PMID- 11009496
TI - Global information flow.
PMID- 11009497
TI - The ethics of international biomedical research.
PMID- 11009499
TI - Why the human rights act matters to doctors.
PMID- 11009498
TI - The management of post-herpetic neuralgia.
PMID- 11009500
TI - Testicular cancer and infertility.
PMID- 11009502
TI - US prescription drug sales boosted by advertising.
PMID- 11009501
TI - The separating of conjoined twins.
PMID- 11009503
TI - Conjoined twins should be separated.
PMID- 11009504
TI - Laparoscopic surgery: two thirds of injuries initially missed.
PMID- 11009505
TI - Shipman inquiry to be held in public.
PMID- 11009506
TI - In brief
PMID- 11009507
TI - Mammography is no better than physical examination, study shows
PMID- 11009508
TI - Public criticism makes paediatric surgeon's job too difficult.
PMID- 11009509
TI - New sweet potato could help combat blindness in Africa.
PMID- 11009510
TI - Government policies set to narrow "health gap".
PMID- 11009511
TI - Global health agencies are accused of incompetence.
PMID- 11009512
TI - WHO links with consumers on reproductive health information.
PMID- 11009513
TI - AIDS vaccine research focuses on subtypes in developed world.
PMID- 11009514
TI - Toiling in tough times.
PMID- 11009515
TI - Risk of testicular cancer in men with abnormal semen characteristics: cohort
study.
AB - OBJECTIVE: To explore the associations between semen characteristics and
subsequent risk of testicular cancer. DESIGN: Cohort study. PARTICIPANTS: 32 442
men who had a semen analysis done at the Sperm Analysis Laboratory in Copenhagen
during 1963-95. MAIN OUTCOME MEASURE: Standardised incidence ratios of testicular
cancer compared with total population of Danish men. RESULTS: Men in couples with
fertility problems were more likely to develop testicular cancer than other men
(89 cases, standardised incidence ratio 1.6; 95% confidence interval 1.3 to 1.9).
The risk was relatively constant with increasing time between semen analysis and
cancer diagnosis. Analysis according to specific semen characteristics showed
that low semen concentration (standardised incidence ratio 2.3), poor motility of
the spermatozoa (2.5), and high proportion of morphologically abnormal
spermatozoa (3.0) were all associated with an increased risk of testicular
cancer. The only other cancer group that showed increased incidence was
"peritoneum and other digestive organs" (six cases; 3.7, 1.3 to 8.0). Of these,
two cases were probably and two cases were possibly extragonadal germ cell
tumours. CONCLUSIONS: The results point towards the existence of common
aetiological factors for low semen quality and testicular cancer. Low semen
quality may also be associated with increased incidence of extragonadal germ cell
tumours.
PMID- 11009516
TI - Towards evidence based circumcision of English boys: survey of trends in
practice.
PMID- 11009517
TI - Wise words
PMID- 11009518
TI - Prevalence of postherpetic neuralgia after a first episode of herpes zoster:
prospective study with long term follow up.
AB - OBJECTIVE: To estimate the frequency, duration, and clinical importance of
postherpetic neuralgia after a single episode of herpes zoster. DESIGN:
Prospective cohort study with long term follow up. SETTING: Primary health care
in Iceland. PARTICIPANTS: 421 patients with a single episode of herpes zoster.
MAIN OUTCOME MEASURES: Age and sex distribution of patients with herpes zoster,
point prevalence of postherpetic neuralgia, and severity of pain at 1, 3, 6, and
12 months and up to 7.6 years after the outbreak of zoster. RESULTS: Among
patients younger than 60 years, the risk of postherpetic neuralgia three months
after the start of the zoster rash was 1.8% (95% confidence interval 0.59% to
4.18%) and pain was mild in all cases. In patients 60 years and older, the risk
of postherpetic neuralgia increased but the pain was usually mild or moderate.
After three months severe pain was recorded in two patients older than 60 years
(1.7%, 2.14% to 6.15%). After 12 months no patient reported severe pain and 14
patients (3.3%) had mild or moderate pain. Seven of these became pain free within
two to seven years, and five reported mild pain and one moderate pain after 7.6
years of follow up. Sex was not a predictor of postherpetic neuralgia. Possible
immunomodulating comorbidity (such as malignancy, systemic steroid use, diabetes)
was present in 17 patients. CONCLUSIONS: The probability of longstanding pain of
clinical importance after herpes zoster is low in an unselected population of
primary care patients essentially untreated with antiviral drugs.
PMID- 11009519
TI - Disseminating health information in developing countries: the role of the
internet.
PMID- 11009520
TI - Addressing men's health issues
PMID- 11009521
TI - Science, medicine, and the future: Leishmaniasis.
PMID- 11009522
TI - Tulips for sale
PMID- 11009523
TI - ABC of colorectal cancer: Epidemiology.
PMID- 11009525
TI - Strengthening health research capacity in developing countries: a critical
element for achieving health equity.
PMID- 11009524
TI - Why has so little changed in maternal and child health in south Asia?
PMID- 11009526
TI - Health technology transfer.
PMID- 11009527
TI - Coordinating health research to promote action: the Tanzanian experience.
PMID- 11009528
TI - A new look at international research ethics.
PMID- 11009529
TI - The greater miracle
PMID- 11009530
TI - Moving to research partnerships in developing countries.
PMID- 11009532
TI - Promoting community health: from pholela to jerusalem
PMID- 11009531
TI - Disaster relief and development could be twinned in health research.
PMID- 11009533
TI - Knowledge can flow from developing to developed countries.
PMID- 11009534
TI - Let's consider ethics of medical practice first.
PMID- 11009535
TI - Information gaps have the same causes as wealth gaps.
PMID- 11009537
TI - Don't forget traditional medical care.
PMID- 11009536
TI - Improving access to reliable information in developing countries.
PMID- 11009538
TI - Asking "how?" rather than "what, why, where, and who?".
PMID- 11009539
TI - Let's start helping our neighbour.
PMID- 11009540
TI - Researching on a shoestring in Colombia.
PMID- 11009541
TI - Community participation is essential in clinical trials.
PMID- 11009542
TI - Effect of drug patents in developing countries.
PMID- 11009543
TI - Vaccines and medicines for the world's poorest. Quality of vaccines and medicines
must be monitored.
PMID- 11009545
TI - When public health may not be public health.
PMID- 11009544
TI - Vaccines and medicines for the world's poorest. Attempts of global forum for
health research should be viewed with optimistic scepticism.
PMID- 11009546
TI - Accurate figures would help to assess countries' needs better.
PMID- 11009548
TI - According to the charity public concern at work
PMID- 11009547
TI - Maternal mortality and mothers' deaths as development indicators.
PMID- 11009549
TI - The disability discrimination act requires employers to make
PMID- 11009550
TI - Doctors who wish to work in developing countries should
PMID- 11009551
TI - A pair of ACEs, for openers?
PMID- 11009552
TI - Targeting Rho in cardiovascular disease.
PMID- 11009553
TI - Na(+)-Ca(2+) exchange in failing myocardium: friend or foe?
PMID- 11009554
TI - Novel genes for mitogen-independent smooth muscle replication.
PMID- 11009555
TI - Tails of the L-type Ca(2+) channel: to sense oxygen or not.
PMID- 11009556
TI - Splice variants reveal the region involved in oxygen sensing by recombinant human
L-type Ca(2+) channels.
AB - Regulation of vascular smooth muscle Ca(2+) channels by oxygen tension
contributes importantly to hypoxic vasodilatation. We previously described the
inhibitory effects of hypoxia on the recombinant human cardiac L-type Ca(2+)
channel alpha(1C) subunit (hHT isoform) expressed in HEK 293 cells. We now
demonstrate that hypoxia inhibits only one of the three naturally occurring
splice variants of this channel that differ only in the C-terminal domain,
permitting identification of a 71-amino acid insert in the C-terminal region of
the channel that confers oxygen sensitivity. Selective restriction of the spliced
insert allowed determination of a 39-amino acid region essential for oxygen
sensing. This represents the first identification of the structural region of an
ion channel required for sensing changes in oxygen tension.
PMID- 11009557
TI - Nitric oxide activates telomerase and delays endothelial cell senescence.
PMID- 11009558
TI - The preconditioning phenomenon: A tool for the scientist or a clinical reality?
AB - The possibility that an innate mechanism of myocardial protection might be
inducible in the human heart has generated considerable excitement and
enthusiastic research. The potential to enhance myocardial resistance to ischemic
injury in patients suffering the consequences of coronary artery disease has led
to studies with more direct clinical relevance. However, in common with many
other areas of clinical interest based on advances in basic scientific
understanding, early enthusiasm may be disproportionate to ultimate therapeutic
significance. There can be little doubt that our understanding of the mechanisms
underlying the pathogenesis of ischemia-reperfusion injury has been enhanced
significantly by the plethora of research stimulated by interest in endogenous
myocardial protection. Direct extrapolation of observations in the laboratory to
the cardiology clinic or operating theater is tempting but should be avoided. The
results of recent clinical experiments that suggest that preconditioning can
protect against ischemia, although encouraging, should be interpreted cautiously,
with particular attention to the limitations of the end points available. A
reasoned evaluation of recent research should prevent unrealistic expectations
and allow improved design of future trials so that this potent adaptive
phenomenon can be exploited to its maximum potential.
PMID- 11009559
TI - Angiotensin II-induced Ca(2+) influx in renal afferent and efferent arterioles:
differing roles of voltage-gated and store-operated Ca(2+) entry.
AB - Angiotensin II (Ang II)-induced Ca(2+) signaling was studied in isolated rat
renal arterioles using fura-2. Ang II (10 nmol/L) caused a sustained elevation in
[Ca(2+)](i), which was dependent on [Ca(2+)](o) in both vessel types. This
response was blocked by nifedipine in only the afferent arteriole. Using the
Mn(2+) quench technique, we found that Ang II stimulates Ca(2+) influx in both
vessels. Nifedipine blocked the Ang II-induced Ca(2+) influx in afferent
arterioles but not in efferent arterioles. In contrast to Ang II, KCl-induced
depolarization stimulated Ca(2+) influx in only the afferent arteriole.
Cyclopiazonic acid (CPA, 30 micromol/L) was used to examine the presence of store
operated Ca(2+) entry in myocytes isolated from each arteriole. In efferent
myocytes, CPA induced a sustained Ca(2+) increase that was dependent on
[Ca(2+)](o) and insensitive to nifedipine. This mechanism was absent in afferent
myocytes. SKF 96365 inhibited Ang II-induced Ca(2+) entry in efferent arterioles
and CPA-induced Ca(2+) entry in efferent myocytes over identical concentrations.
Our findings thus indicate that Ang II activates differing Ca(2+) influx
mechanisms in pre- and postglomerular arterioles. In the afferent arteriole, Ang
II activates dihydropyridine-sensitive L-type Ca(2+) channels, presumably by
membrane depolarization. In the efferent arteriole, Ang II appears to stimulate
Ca(2+) entry via store-operated Ca(2+) influx.
PMID- 11009560
TI - Early activation of the multicomponent signaling complex associated with focal
adhesion kinase induced by pressure overload in the rat heart.
AB - Mechanical overload elicits functional and structural adaptive mechanisms in
cardiac muscle. Signaling pathways linked to integrin/cytoskeleton complexes may
have a function in mediation of the effects of mechanical stimulus in myocardial
cells. We investigated the tyrosine phosphorylation and the assembly of the
multicomponent signaling complex associated with focal adhesion kinase (Fak) and
the actin cytoskeleton in the overloaded myocardium of rats. Pressure overload
induced a 3-fold increase in Fak tyrosine phosphorylation within 3 minutes after
a 60-mm Hg rise in aortic pressure. A pressure stimulus that lasted for 60
minutes was accompanied by a 5-fold increase in the amount of tyrosine
phosphorylated Fak, and a stimulus as low as 10 mm Hg doubled the amount of
tyrosine-phosphorylated Fak in the myocardium within 10 minutes. Pressure
overload also induced a time-dependent association of actin with Fak and an
increase in the amount of Fak detected in the cytoskeletal fraction of the
myocardium. These events were paralleled by c-Src activation and binding to Fak
and by an association of Grb2 and p85 subunit of phosphatidylinositol 3-kinase
with Fak. Erk1/2 and Akt, two possible downstream effectors of Fak via Grb2 and
phosphatidylinositol 3-kinase, were also shown to be activated in parallel with
Fak. These findings show that pressure overload induced a rapid activation of the
Fak multiple signaling complex in the myocardium of rats, which suggests that
this mechanism may have a role in mechanotransduction in the myocardium.
PMID- 11009561
TI - Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and
vascular oxidative stress in the aortas of insulin-resistant rats.
AB - We have reported that a deficiency of tetrahydrobiopterin (BH(4)), an active
cofactor of endothelial NO synthase (eNOS), contributes to the endothelial
dysfunction through reduced eNOS activity and increased superoxide anion (O(2)(
)) generation in the insulin-resistant state. To further confirm this hypothesis,
we investigated the effects of dietary treatment with BH(4) on endothelium
dependent arterial relaxation and vascular oxidative stress in the aortas of
insulin-resistant rats. Oral supplementation of BH(4) (10 mg. kg(-1). d(-1)) for
8 weeks significantly increased the BH(4) content in cardiovascular tissues of
rats fed high levels of fructose (fructose-fed rats). Impairment of endothelium
dependent arterial relaxation in the aortic strips of the fructose-fed rats was
reversed with BH(4) treatment. The BH(4) treatment was associated with a 2-fold
increase in eNOS activity as well as a 70% reduction in endothelial O(2)(-)
production compared with those in fructose-fed rats. The BH(4) treatment also
partially improved the insulin sensitivity and blood pressure, as well as the
serum triglyceride concentration, in the fructose-fed rats. Moreover, BH(4)
treatment of the fructose-fed rats markedly reduced the lipid peroxide content of
both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive
transcription factors, nuclear factor-kappaB and activating protein-1, which were
increased in fructose-fed rats. The BH(4) treatment of control rats did not have
any significant effects on these parameters. These results indicate that BH(4)
augmentation is essential for the restoration of eNOS function and the reduction
of vascular oxidative stress in insulin-resistant rats.
PMID- 11009562
TI - Hyperglycemia inhibits vascular smooth muscle cell apoptosis through a protein
kinase C-dependent pathway.
AB - We hypothesized that the pathogenesis of diabetic vasculopathy involves the
abnormal regulation of vascular smooth muscle cell (VSMC) apoptosis. In
nondiabetic mice, a reduction in carotid artery blood flow resulted in a
significant loss of medial VSMCs via apoptosis (normal flow 84+/-1 viable VSMCs,
reduced flow 70+/-5 viable VSMCs; n=12, P:<0.01). In contrast, flow-induced VSMC
apoptosis was markedly attenuated in streptozotocin-induced diabetic mice (normal
flow 85+/-2 viable VSMC, reduced flow 82+/-4 viable VSMC; n=13, NS). In accord
with our in vivo findings, the exposure of cultured rat and human VSMCs to high
glucose (17.5 mmol/L) significantly attenuated the induction of apoptosis in
response to serum withdrawal (rat VSMCs in normal [5.5 mmol/L] glucose 28+/-1%,
high D-glucose 19+/-2%; P:<0.0001). High glucose also inhibited apoptosis induced
by Fas ligand (100 ng/mL) (normal 23+/-2%, high D-glucose 13+/-2%; P:<0.006).
Supplementation with the nonmetabolized enantiomer L-glucose had no effect. We
confirmed reports that high glucose activates protein kinase C (PKC) and
demonstrated that PKC blockade with long-term phorbol ester treatment or
calphostin C prevented the antiapoptotic effect (P:<0. 001). Moreover, the
upregulation of either PKCalpha or PKCbetaII expression was sufficient to inhibit
serum withdrawal-induced apoptosis (control 25+/-2%, PKCalpha 11+/-2%, PKCbetaII
8+/-2%; P:<0. 0001), whereas the upregulation of PKCdelta had no significant
effect. Taken together, these findings demonstrate that hyperglycemia inhibits
VSMC apoptosis via a PKC-dependent pathway.
PMID- 11009563
TI - Impaired contractile performance of cultured rabbit ventricular myocytes after
adenoviral gene transfer of Na(+)-Ca(2+) exchanger.
AB - Na(+)-Ca(2+) exchanger (NCX) gene expression is increased in the failing human
heart. We investigated the hypothesis that upregulation of NCX can induce
depressed contractile performance. Overexpression of NCX was achieved in isolated
rabbit ventricular myocytes through adenoviral gene transfer (Ad-NCX). After 48
hours, immunoblots revealed a virus dose-dependent increase in NCX protein.
Adenoviral beta-galactosidase transfection served as a control. The fractional
shortening (FS) of electrically stimulated myocytes was analyzed. At 60 min(-1),
FS was depressed by 15.6% in the Ad-NCX group (n=143) versus the control group
(n=163, P:<0.05). Analysis of the shortening-frequency relationship showed a
steady increase in FS in the control myocytes (n=26) from 0.027+/-0.002 at 30
min(-1) to 0. 037+/-0.002 at 120 min(-1) (P:<0.05 versus 30 min(-1)) and to 0.
040+/-0.002 at 180 min(-1) (P:<0.05 versus 30 min(-1)). Frequency potentiation of
shortening was blunted in NCX-transfected myocytes (n=27). The FS was 0.024+/
0.002 at 30 min(-1), 0.029+/-0.002 at 120 min(-1) (P:<0.05 versus 30 min(-1),
P:<0.05 versus control), and 0. 026+/-0.002 at 180 min(-1) (NS versus 30 min(-1),
P:<0.05 versus control). Caffeine contractures, which indicate sarcoplasmic
reticulum Ca(2+) load, were significantly reduced at 120 min(-1) in NCX
transfected cells. An analysis of postrest behavior showed a decay of FS with
longer rest intervals in control cells. Rest decay was significantly higher in
the Ad-NCX group; after 120 seconds of rest, FS was 78+/-4% in control and 65+/
3% in the Ad-NCX group (P:<0.05) relative to steady-state FS before rest (100%).
In conclusion, the overexpression of NCX in rabbit cardiomyocytes results in the
depression of contractile function. This supports the hypothesis that
upregulation of NCX can result in systolic myocardial failure.
PMID- 11009564
TI - Contractile reserve and intracellular calcium regulation in mouse myocytes from
normal and hypertrophied failing hearts.
AB - Mouse myocyte contractility and the changes induced by pressure overload are not
fully understood. We studied contractile reserve in isolated left ventricular
myocytes from mice with ascending aortic stenosis (AS) during compensatory
hypertrophy (4-week AS) and the later stage of early failure (7-week AS) and from
control mice. Myocyte contraction and [Ca(2+)](i) transients with fluo-3 were
measured simultaneously. At baseline (0.5 Hz, 1.5 mmol/L [Ca(2+)](o), 25 degrees
C), the amplitude of myocyte shortening and peak-systolic [Ca(2+)](i) in 7-week
AS were not different from those of controls, whereas contraction, relaxation,
and the decline of [Ca(2+)](i) transients were slower. In response to the
challenge of high [Ca(2+)](o), fractional cell shortening was severely depressed
with reduced peak-systolic [Ca(2+)](i) in 7-week AS compared with controls. In
response to rapid pacing stimulation, cell shortening and peak-systolic
[Ca(2+)](i) increased in controls, but this response was depressed in 7-week AS.
In contrast, the responses to both challenge with high [Ca(2+)](o) and rapid
pacing in 4-week AS were similar to those of controls. Although protein levels of
Na(+)-Ca(2+) exchanger were increased in both 4-week and 7-week AS, the ratio of
SR Ca(2+)-ATPase to phospholamban protein levels was depressed in 7-week AS
compared with controls but not in 4-week AS. This was associated with an impaired
capacity to increase sarcoplasmic reticulum Ca(2+) load during high work states
in 7-week AS myocytes. In hypertrophied failing mouse myocytes, depressed
contractile reserve is related to an impaired augmentation of systolic
[Ca(2+)](i) and SR Ca(2+) load and simulates findings in human failing myocytes.
PMID- 11009565
TI - Peroxisome proliferator-activated receptor activators inhibit lipopolysaccharide
induced tumor necrosis factor-alpha expression in neonatal rat cardiac myocytes.
AB - Peroxisome proliferator-activated receptors (PPARs) are transcription factors
belonging to the nuclear receptor superfamily. Recently, PPAR activators have
been shown to inhibit the production of proinflammatory cytokines in macrophages
or vascular smooth muscle cells. It has been reported that tumor necrosis factor
alpha (TNF-alpha) expression is elevated in the failing heart and that TNF-alpha
has a negative inotropic effect on cardiac myocytes. Therefore, we examined the
effects of PPARalpha and PPARgamma activators on expression of TNF-alpha in
neonatal rat cardiac myocytes. Northern blot analysis revealed expression of
PPARalpha and PPARgamma mRNA in cardiac myocytes. Immunofluorescent staining
demonstrated that both PPARalpha and PPARgamma were expressed in the nuclei of
cells. When cardiac myocytes were transfected with PPAR responsive element (PPRE)
luciferase reporter plasmid, both PPARalpha and PPARgamma activators increased
the promoter activity. Cardiomyocytes were stimulated with lipopolysaccharide
(LPS), and the levels of TNF-alpha in the medium were measured by ELISA. After
exposure to LPS, the levels of TNF-alpha significantly increased. However,
pretreatment of myocytes with PPARalpha or PPARgamma activators decreased LPS
induced expression of TNF-alpha in the medium. Both PPARalpha and PPARgamma
activators also inhibited LPS-induced increase in TNF-alpha mRNA in myocytes. In
addition, electrophoretic mobility shift assays demonstrated that PPAR activators
reduced LPS-induced nuclear factor-kappaB activation. These results suggest that
both PPARalpha and PPARgamma activators inhibit cardiac expression of TNF-alpha
in part by antagonizing nuclear factor-kappaB activity and that treatment with
PPAR activators may lead to improvement in congestive heart failure.
PMID- 11009566
TI - Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and
targets cell junctions.
AB - Inflammation is a basic pathological mechanism that underlies many diseases. An
important component of the inflammatory response is the passage of plasma
components and leukocytes from the blood vessel into the tissues. The endothelial
monolayer lining blood vessels reacts to stimuli such as thrombin or vascular
endothelial growth factor by changes in cell-cell junctions, an increase in
permeability, and the leakage of plasma components into tissues. Other stimuli,
such as tumor necrosis factor-alpha (TNF-alpha), are responsible for stimulating
the transmigration of leukocytes. Here we show that angiopoietin-1, a cytokine
essential in fetal angiogenesis, not only supports the localization of proteins
such as platelet endothelial cell adhesion molecule-1 (PECAM-1) into junctions
between endothelial cells and decreases the phosphorylation of PECAM-1 and
vascular endothelial cadherin, but it also strengthens these junctions, as
evidenced by a decrease in basal permeability and inhibition of permeability
responses to thrombin and vascular endothelial growth factor. Furthermore,
angiopoietin-1 inhibits TNF-alpha-stimulated leukocyte transmigration.
Angiopoietin-1 may thus have a major role in maintaining the integrity of
endothelial monolayers.
PMID- 11009567
TI - Novel embryonic genes are preferentially expressed by autonomously replicating
rat embryonic and neointimal smooth muscle cells.
AB - We sought to identify and characterize the expression pattern of genes expressed
by smooth muscle cells (SMCs) during periods of self-driven replication during
vascular development and after vascular injury. Primary screening of a rat
embryonic aortic SMC-specific cDNA library was accomplished with an autonomous
embryonic SMC-enriched, nonautonomous adult SMC-subtracted cDNA probe. Positive
clones were rescreened in parallel with embryonic SMC-specific and adult SMC
specific cDNA probes. We identified 14 clones that hybridized only with the
embryonic cDNA ("emb" clones), 11 of which did not share significant homology
with sequences in any of the databases. Five of these novel emb genes (emb7,
emb8, emb20, emb37, and emb41) were selectively and only transiently reexpressed
in vivo by neointimal SMCs during periods of rapid replication. The
emb8:embryonic growth-associated protein (EGAP), which was studied the most
extensively, was expressed at high levels by cultured, autonomously replicating
embryonic and neointimal SMCs but was detected only at low levels even in
mitogenically stimulated adult SMCs. Finally, the administration of antisense
EGAP oligonucleotides markedly attenuated embryonic and neointimal SMC
replication rates. We suggest that autonomous replication of SMCs may be
essential for normal vascular morphogenesis and for the vascular response to
injury and that these newly identified "embryonic" genes may be part of the
molecular machinery that drives this unique growth phenotype.
PMID- 11009568
TI - Involvement of Rho GTPases in the transcriptional inhibition of preproendothelin
1 gene expression by simvastatin in vascular endothelial cells.
AB - Endothelial dysfunction is characterized by an impaired vasodilatory response to
endothelial agonists as well as by alterations in adhesion and coagulation
processes. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) have
been shown to be useful in the reversal of endothelial dysfunction, an effect
that may be independent of the reduction in cholesterol levels. Both the L
arginine-nitric oxide-cGMP and endothelin pathways are involved in the regulation
of vascular tone. Here, we show that the basal transcription rate of the
preproendothelin-1 gene was decreased by simvastatin (10 micromol/L) in bovine
aortic endothelial cells. Transfection studies with the preproendothelin-1 gene
promoter showed that mevalonate (100 micromol/L) was able to prevent the
inhibitory effect mediated by simvastatin. Protein geranylgeranylation, but not
farnesylation, proved to be crucial for a correct expression of the
preproendothelin-1 gene. The C3 exotoxin from Clostridium botulinum that
selectively inactivates Rho GTPases, the processing of which involves
geranylgeranylation, reproduced the inhibitory effect of simvastatin on the
expression of preproendothelin-1. Overexpression of dominant-negative mutants of
RhoA and RhoB led to a significant reduction in the preproendothelin-1 promoter
activity, whereas the expression of wild-type and constitutively active forms of
these proteins resulted in an increase, in support that Rho proteins are required
for the basal expression of the preproendothelin-1 gene. Finally, we show that
the Rho-dependent activation of the preproendothelin-1 gene transcription was
inhibited by simvastatin. Thus, the control of vascular tone and proliferative
response mediated by endothelin-1 is regulated at multiple levels, among which
the Rho proteins play an essential role.
PMID- 11009569
TI - A comparison of aorta and vena cava medial message expression by cDNA array
analysis identifies a set of 68 consistently differentially expressed genes, all
in aortic media.
AB - We performed a systematic analysis of gene expression in arteries and veins by
comparing message profiles of macaque aorta and vena cava media using a cDNA
array containing 4048 known human genes, approximately 35% of currently named
human genes (approximately 11,000). The data show extensive differences in RNA
expression in artery versus vein media. Sixty-eight genes had consistent
elevation in message expression by the aorta, but none were elevated in the vena
cava. The most differentially expressed gene was regulator of G-protein signaling
(RGS) 5, at an expression ratio of 46.5+/-12.6 (mean+/-SEM). The data set also
contained 2 genes already known to be expressed in the aorta, elastin at 5.0+/
1.4, and the aortic preferentially expressed gene 1 (APEG-1) at 2.3+/-0.6. We
chose to analyze RGS5 expression further because of its high level of
differential expression in the aorta. Levels of RGS5 mRNA were confirmed by
Northern analysis and in situ hybridization. A human tissue RNA dot blot showed
that RGS5 message is highest in aorta, followed by small intestine, stomach, and
then heart. Northern analysis confirmed that RGS5 expression in human aorta is
higher than in any region of the heart. RGS5 is a G-protein signaling regulator
of unknown specificity most homologous to RGS4, an inhibitory regulator of
pressure-induced cardiac hypertrophy. The expression pattern of the 68
differential genes as a whole is a start toward identifying the molecular
phenotypes of arteries and veins on a systematic basis.
PMID- 11009570
TI - Phosphate regulation of vascular smooth muscle cell calcification.
AB - Vascular calcification is a common finding in atherosclerosis and a serious
problem in diabetic and uremic patients. Because of the correlation of
hyperphosphatemia and vascular calcification, the ability of extracellular
inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC)
culture mineralization in vitro was examined. HSMCs cultured in media containing
normal physiological levels of inorganic phosphate (1.4 mmol/L) did not
mineralize. In contrast, HSMCs cultured in media containing phosphate levels
comparable to those seen in hyperphosphatemic individuals (>1.4 mmol/L) showed
dose-dependent increases in mineral deposition. Mechanistic studies revealed that
elevated phosphate treatment of HSMCs also enhanced the expression of the
osteoblastic differentiation markers osteocalcin and Cbfa-1. The effects of
elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate
cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor
phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium
deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of
polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was
identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data
suggest that elevated phosphate may directly stimulate HSMCs to undergo
phenotypic changes that predispose to calcification and offer a novel explanation
of the phenomenon of vascular calcification under hyperphosphatemic conditions.
The full text of this article is available at http://www.circresaha.org.
PMID- 11009571
TI - iNOS gene expression modulates microvascular responsiveness in endotoxin
challenged mice.
AB - Septic shock is characterized by vasodilation and decreased responsiveness to
vasoconstrictors. Recent studies suggest this results from nitric oxide (NO)
overproduction after expression of the calcium-independent isoform of NO synthase
(iNOS) in smooth muscle cells. However, direct evidence linking iNOS (NOS2)
expression and decreased microvascular responsiveness after septic stimuli is
lacking. In the present study, we determined the effect of bacterial
lipopolysaccharide (LPS, 20 mg/kg, IP) on smooth muscle contraction and
endothelial relaxation in mesenteric resistance arteries from wild-type and iNOS
knockout mice. Four hours after challenge with LPS or saline in vivo,
concentration-dependent responses to norepinephrine (NE) and acetylcholine
(NE+ACh) were measured in cannulated, pressurized vessels ex vivo. In vessels
from wild-type mice, NE-induced contraction was markedly impaired after LPS, and
pretreatment with the iNOS inhibitor aminoguanidine (AG) partly restored the NE
contraction. In contrast, NE contraction in microvessels from iNOS knockout mice
was unaffected by LPS. ACh-induced relaxation was unaffected by LPS in vessels
from either genotype. These data provide direct evidence that iNOS gene
expression mediates the LPS-induced decrease in microvascular responsiveness to
vasoconstrictors. Moreover, the observation that AG did not fully restore NE
contraction after LPS, whereas iNOS gene deficiency did, suggests that iNOS
expression plays a central role in the development of the NO-independent effect
of LPS on microvascular responsiveness. Finally, our data indicate that LPS or
iNOS expression has little effect on endothelium-dependent relaxation, and eNOS
activity does not appear to play a role in the decreased smooth muscle
responsiveness after LPS in this model. The full text of this article is
available at http://www.circresaha.org.
PMID- 11009572
TI - Challenges in medical education-what the doctor ordered?
PMID- 11009574
TI - A lay doctor's guide to the inflammatory process in the gastrointestinal tract.
PMID- 11009573
TI - Pharmacological treatment of Parkinson's disease.
PMID- 11009575
TI - Review of cryptogenic fibrosing alveolitis, including current treatment
guidelines.
PMID- 11009576
TI - Association of anticardiolipin antibodies with vascular injury: possible
mechanisms.
PMID- 11009578
TI - Emptiness of the left iliac fossa: a new clinical sign of sigmoid volvulus.
AB - BACKGROUND: Diagnostic difficulties are common in sigmoid volvulus. This
diagnostic delay contributes to high morbidity and mortality. AIM: This paper
recognises visible or palpable emptiness of the left iliac fossa as a new
clinical sign of sigmoid volvulus. Predictive accuracy of the sign was assessed
in this study. METHODS: 519 patients with acute abdomen of non-traumatic origin
were prospectively studied. RESULTS: The new sign was present in 24 out of 86
patients (28%) with sigmoid volvulus. It was absent in all those who did not have
sigmoid volvulus. The positive predictive value of the sign was 100%. CONCLUSION:
Emptiness of the left iliac fossa is a valuable diagnostic adjunct. Positive sign
is pathognomonic of sigmoid volvulus. Nevertheless, a negative sign warrants
further investigations.
PMID- 11009579
TI - Single photon emission computed tomography in tuberculous meningitis.
AB - INTRODUCTION: Data on single photon emission computed tomography (SPECT) in
tuberculous meningitis are lacking and prompted this study. SPECT findings in
tuberculous meningitis are reported and correlated with clinical and radiological
findings. PATIENTS AND METHODS: Seventeen patients with tuberculous meningitis
that was diagnosed on clinical, radiological, and laboratory criteria have been
included. Their age ranged between 5 and 62 years and four of them were female.
Computed tomography and/or magnetic resonance imaging (MRI) and SPECT using
(99m)Tc-ethylene cystine dimer were performed in all the patients. On the basis
of Barthel index (BI) score the patients' outcome was defined as complete (BI =
20), partial (BI = 19-12), and poor recovery (BI<12). RESULT: Eleven patients
were in stage III and three each in stage II and stage I tuberculous meningitis.
Two patients had hemiplegia and five quadriplegia. Computed tomography was
abnormal in 11 out of 16 patients and revealed hydrocephalus in nine, basal
exudates, infarction in subcortical white matter and basal ganglia in six
patients each, frontal cortical infarction in one, and granulomata in three
patients. Cranial MRI was carried out in four patients and revealed multiple
granulomata, hydrocephalus, and brainstem infarction in two patients each. SPECT
studies were abnormal in all except two patients and revealed hypoperfusion of
the basal ganglia in 14, cortical hypoperfusion in 10, and midbrain hypoperfusion
in one patient. At the three month follow up four patients had died, five had
poor, three partial, and five complete recovery. The SPECT studies were more
frequently abnormal compared with computed tomography but did not correlate with
stage of meningitis or outcome. CONCLUSION: In tuberculous meningitis subcortical
and cortical hypoperfusion is common but it does not correlate with stage of
meningitis or three month outcome.
PMID- 11009577
TI - Behcet's disease.
AB - Behcet's disease is a systemic vasculitis of unknown aetiology characteristically
affecting venules. Onset is typically in young adults with recurrent oral and
genital ulceration, uveitis, skin manifestations, arthritis, neurological
involvement, and a tendency to thrombosis. It has a worldwide distribution but is
prevalent in Japan, the Middle East, and some Mediterranean countries.
International diagnostic criteria have been proposed, however diagnosis can be
problematical, particularly if the typical ulcers are not obvious at
presentation. Treatment is challenging, must be tailored to the pattern of organ
involvement for each patient and often requires combination therapies.
PMID- 11009580
TI - Closed pelvic fractures: characteristics and outcomes in older patients admitted
to medical and geriatric wards.
AB - OBJECTIVE: To investigate the characteristics and outcomes of older patients with
pelvic fracture admitted to medical and geriatric wards. METHODS: All patients
admitted to medical and geriatric wards with a pelvic fracture over a four year
period were identified using the hospital clinical coding database. Data were
collected from casenotes, hospital and Family Health Services Authority
databases. Where available, pelvic radiographs were graded according to the Singh
index. RESULTS: The casenotes of 148 patients (126 women) were studied; 83%
(n=123) of patients suffered a pelvic fracture in low energy trauma. Mean (SD)
length of hospital stay was 21.3 (17.6) days. Single breaks of the pubic rami
accounted for 47.2% (n=68) of all fractures. Inpatient mortality was 7.6% and at
one year was 27%. There was a marked adverse effect on the mobility of survivors
with all patients using at least a walking stick at discharge and 51.1% (n=70)
needing assistance for mobility. Although 70.9% (n=83) of patients admitted from
home (or warden aided accommodation) were able to return there, 84.3% (n=70) of
them required extra community support. Rates of institutionalisation rose from
20.9% (n=31) at admission to 35.8% (49/137) of survivors at discharge. Altogether
93% (n=107) of 115 patients, in whom adequate quality pelvic radiographs were
available, were assigned a Singh index grade of 4 or less indicating the presence
of osteoporosis. CONCLUSIONS: Pelvic fractures are often the result of low energy
trauma. They are associated with appreciable inpatient and considerable one year
mortality. They also have marked negative effects on mobility in the short term.
They result in increased levels of dependency in terms of higher levels of
community support and rates of institutionalisation. On the evidence of Singh
index grading, pelvic fractures are associated with low bone density.
PMID- 11009581
TI - QT prolongation due to roxithromycin.
PMID- 11009582
TI - Commentary-QT prolongation due to roxithromycin.
PMID- 11009583
TI - An unusual case of pyrexia of unknown origin with cervical lymphadenopathy.
AB - Kikuchi's disease is usually a self limiting illness characterised by pyrexia,
neutropenia, and cervical lymphadenopathy particularly in young women of Asian
descent. This often leads to an initial misdiagnosis of lymphoma. A case of a
young Asian woman who presented with pyrexia of unknown origin is described.
PMID- 11009584
TI - Carotid sinus syndrome masquerading as treatment resistant epilepsy.
AB - A 65 year old woman had a 12 year history of frequent, recurrent seizure-like
episodes labelled as treatment resistant epilepsy after neurological evaluation
and follow up and treatment with multiple antiepileptic medications. Carotid
sinus massage provoked 5.6 seconds asystole with symptom reproduction, and she
has remained symptom-free after permanent pacemaker implantation for her carotid
sinus syndrome and withdrawal of antiepileptic medications.
PMID- 11009585
TI - Chorea disclosing deterioration of polycythaemia vera.
AB - Neurological manifestations occur frequently in polycythaemia. Chorea, however,
is a rare complication of the disease. A case of chorea in a patient previously
diagnosed with polycythaemia vera is reported. Choreic movements started after
measurement of haematological variables showed deterioration. It was considered
that this was caused by inappropriate treatment with iron because the chorea was
markedly reduced after the two first venesections and normalisation of the packed
cell volume and haemoglobin parameters.
PMID- 11009586
TI - A case of migratory lymphadenopathy and cutaneous anergy in an Asian woman.
PMID- 11009587
TI - Multiple focal lesions in liver and spleen in acute leukaemia
PMID- 11009588
TI - A pregnant patient with bilateral ischaemic limbs.
PMID- 11009589
TI - Severe symptomatic hypercalcaemia.
PMID- 11009590
TI - A case of migratory lymphadenopathy and cutaneous anergy in an asian woman
PMID- 11009591
TI - Multiple focal lesions in liver and spleen in acute leukaemia.
PMID- 11009592
TI - A pregnant patient with bilateral ischaemic limbs
PMID- 11009593
TI - Severe symptomatic hypercalcaemia
PMID- 11009594
TI - Cultural sensitivity.
PMID- 11009595
TI - The functional association of polymyxin B with bacterial lipopolysaccharide is
stereospecific: studies on polymyxin B nonapeptide.
AB - The Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is a major inducer
of sepsis. The natural cyclic peptide polymyxin B (PMB) is a potent antimicrobial
agent, albeit highly toxic, by virtue of its capacity to neutralize the
devastating effects of LPS. However, the exact mode of association between PMB
and LPS is not clear. In this study, we have synthesized polymyxin B nonapeptide,
the LPS-binding cyclic domain of PMB, and its enantiomeric analogue and studied
several parameters related to their interaction with LPS and their capacity to
sensitize Gram-negative bacteria toward hydrophobic antibiotics. The results
suggest that whereas the binding of the two enantiomeric peptides to E. coli and
to E. coli LPS is rather similar, functional association with the bacterial cell
is stereospecific. Thus, the L-enantiomer is capable of synergism with the
hydrophobic antimicrobial drugs novobiocin and erythromycin, whereas the D
enantiomer is devoid of such activity. The potential of understanding and
consequently utilizing the PMB-LPS association for novel, nontoxic PMB-derived
drugs is discussed.
PMID- 11009596
TI - Biochemical and biophysical characterization of OmpG: A monomeric porin.
AB - A recombinant form of the porin OmpG, OmpGm, lacking the signal sequence, has
been expressed in Escherichia coli. After purification under denaturing
conditions, the protein was refolded in the detergent Genapol X-080, where it
gained a structure rich in beta sheet as evidenced by a CD spectrum similar to
that of the native form. Electrophoretic analysis and limited proteolysis
experiments suggested that refolded OmpGm exists in at least three forms.
Nevertheless, the recombinant protein formed uniform channels in planar bilayers
with a conductance of 0.81 nS (1 M NaCl, pH 7.5). Previous biochemical studies
had suggested that OmpG is a monomeric porin, rather than the usual trimer.
Bilayer recordings substantiated this proposal; voltage-induced closures occurred
consistently in a single step, and channel block by Gd(3+) lacked the
cooperativity seen with the trimeric porin OmpF. The availability of milligram
amounts of a monomeric porin will be useful both for basic studies of porin
function and for membrane protein engineering.
PMID- 11009597
TI - Role of the hinge region and the tryptophan residue in the synthetic
antimicrobial peptides, cecropin A(1-8)-magainin 2(1-12) and its analogues, on
their antibiotic activities and structures.
AB - A 20-residue hybrid peptide CA(1-8)-MA(1-12) (CA-MA), incorporating residues 1-8
of cecropin A (CA) and residues 1-12 of magainin 2 (MA), has potent antimicrobial
activity without toxicity against human erythrocytes. To investigate the effects
of the Gly-Ile-Gly hinge sequence of CA-MA on the antibacterial and antitumor
activities, two analogues in which the Gly-Ile-Gly sequence of CA-MA is either
deleted (P1) or substituted with Pro (P2) were synthesized. The role of the
tryptophan residue at position 2 of CA-MA on its antibiotic activity was also
investigated using two analogues, in which the Trp2 residue of CA-MA is replaced
with either Ala (P3) or Leu (P4). The tertiary structures of CA-MA, P2, and P4 in
DPC micelles, as determined by NMR spectroscopy, have a short amphiphilic helix
in the N-terminus and about three turns of alpha-helix in the C-terminus, with
the flexible hinge region between them. The P1 analogue has an alpha-helix from
Leu4 to Ala14 without any hinge structure. P1 has significantly decreased lytic
activities against bacterial and tumor cells and PC/PS vesicles (3:1, w/w), and
reduced pore-forming activity on lipid bilayers, while P2 retained effective
lytic activities and pore-forming activity. The N-terminal region of P3 has a
flexible structure without any specific secondary structure. The P3 modification
caused a drastic decrease in the antibiotic activities, whereas P4, with the
hydrophobic Leu side chain at position 2, retained its activities. On the basis
of the tertiary structures, antibiotic activities, vesicle-disrupting activities,
and pore-forming activities, the structure-function relationships can be
summarized as follows. The partial insertion of the Trp2 of CA-MA into the
membrane, as well as the electrostatic interactions between the positively
charged Lys residues at the N-terminus of the CA-MA and the anionic phospholipid
headgroups, leads to the primary binding to the cell membrane. Then, the
flexibility or bending potential induced by the Gly-Ile-Gly hinge sequence or the
Pro residue in the central part of the peptides may allow the alpha-helix in the
C-terminus to span the lipid bilayer. These structural features are crucial for
the potent antibiotic activities of CA-MA.
PMID- 11009598
TI - Escherichia coli uracil DNA glycosylase: NMR characterization of the short
hydrogen bond from His187 to uracil O2.
AB - Uracil DNA glycosylase (UDG) cleaves the glycosidic bond of deoxyuridine in DNA
using a hydrolytic mechanism, with an overall catalytic rate enhancement of
10(12)-fold over the solution reaction. The nature of the enzyme-substrate
interactions that lead to this large rate enhancement are key to understanding
enzymatic DNA repair. Using (1)H and heteronuclear NMR spectroscopy, we have
characterized one such interaction in the ternary product complex of Escherichia
coli UDG, the short (2.7 A) H bond between His187 N(epsilon)(2) and uracil O2.
The H bond proton is highly deshielded at 15.6 ppm, indicating a short N-O
distance and exhibits a solvent exchange rate that is 400- and 10(5)-fold slower
than free imidazole at pH 7.5 and pH 10, respectively. Heteronuclear NMR
experiments at neutral pH show that this H bond involves the neutral imidazole
form of His187 and the N1-O2 imidate form of uracil. The excellent correspondence
of the pK(a) for the disappearance of the H bond (pK(a) = 6.3 +/- 0.1) with the
previously determined pK(a) = 6.4 for the N1 proton of enzyme-bound uracil
indicates that the H bond requires negative charge on uracil O2 [Drohat, A. C.,
and Stivers, J. T. (2000) J. Am. Chem. Soc. 122, 1840-1841]. Although the above
characteristics suggest a short strong H bond, the D/H fractionation factor of
phi = 1.0 is more typical of a normal H bond. This unexpected observation may
reflect a large donor-acceptor pK(a) mismatch or the net result of two opposing
effects on vibrational frequencies: decreased N-H bond stretching frequencies
(phi < 1) and increased bending frequencies (phi > 1) relative to the O-H bonds
of water. The role of this H bond in catalysis by UDG and several approaches to
quantify the H bond energy are discussed.
PMID- 11009599
TI - Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric
analysis of the V82F/I84V active site resistant mutant.
AB - One of the most serious side effects associated with the therapy of HIV-1
infection is the appearance of viral strains that exhibit resistance to protease
inhibitors. The active site mutant V82F/I84V has been shown to lower the binding
affinity of protease inhibitors in clinical use. To identify the origin of this
effect, we have investigated the binding thermodynamics of the protease
inhibitors indinavir, ritonavir, saquinavir, and nelfinavir to the wild-type HIV
1 protease and to the V82F/I84V resistant mutant. The main driving force for the
binding of all four inhibitors is a large positive entropy change originating
from the burial of a significant hydrophobic surface upon binding. At 25 degrees
C, the binding enthalpy is unfavorable for all inhibitors except ritonavir, for
which it is slightly favorable (-2.3 kcal/mol). Since the inhibitors are
preshaped to the geometry of the binding site, their conformational entropy loss
upon binding is small, a property that contributes to their high binding
affinity. The V82F/I84V active site mutation lowers the affinity of the
inhibitors by making the binding enthalpy more positive and making the entropy
change slightly less favorable. The effect on the enthalpy change is, however,
the major one. The predominantly enthalpic effect of the V82F/I84V mutation is
consistent with the idea that the introduction of the bulkier Phe side chain at
position 82 and the Val side chain at position 84 distort the binding site and
weaken van der Waals and other favorable interactions with inhibitors preshaped
to the wild-type binding site. Another contribution of the V82F/I84V to binding
affinity originates from an increase in the energy penalty associated with the
conformational change of the protease upon binding. The V82F/I84V mutant is
structurally more stable than the wild-type protease by about 1.4 kcal/mol. This
effect, however, affects equally the binding affinity of substrate and
inhibitors.
PMID- 11009600
TI - Formation of a noncovalent serpin-proteinase complex involves no conformational
change in the serpin. Use of 1H-15N HSQC NMR as a sensitive nonperturbing monitor
of conformation.
AB - A structural understanding of the nature and scope of serpin inhibition
mechanisms has been limited by the inability so far to crystallize any serpin
proteinase complex. We describe here the application of [(1)H-(15)N]-HSQC NMR on
uniformly and residue-selectively (15)N-labeled serpin alpha(1)-proteinase
inhibitor (Pittsburgh variant with stabilizing mutations) to provide a
nonperturbing and exquisitely sensitive means of probing the conformation of the
serpin alone and in a noncovalent complex with inactive, serine 195-modified,
bovine trypsin. The latter should be a good model both for the few examples of
reversible serpin-proteinase complexes and for the initial Michaelis-like complex
formed en route to irreversible covalent inhibition. Cleavage of the reactive
center loop, with subsequent insertion into beta-sheet A, caused dramatic
perturbation of most of the NMR cross-peaks. This was true for both the uniformly
labeled and alanine-specifically labeled samples. The spectra of uniformly or
leucine- or alanine-specifically labeled alpha(1)-proteinase inhibitor in
noncovalent complex with unlabeled inactive trypsin gave almost no detectable
chemical shift changes of cross-peaks, but some general increase in line width.
Residue-specific assignments of the four alanines in the reactive center loop, at
P12, P11, P9, and P4, allowed specific examination of the behavior of the
reactive center loop. All four alanines showed higher mobility than the body of
the serpin, consistent with a flexible reactive center loop, which remained
flexible even in the noncovalent complex with proteinase. The three alanines near
the hinge point for insertion showed almost no chemical shift perturbation upon
noncovalent complex formation, while the alanine at P4 was perturbed, presumably
by interaction with the active site of bound trypsin. Reporters from both the
body of the serpin and the reactive center loop therefore indicate that
noncovalent complex formation involves no conformational change in the body of
the serpin and only minor perturbation of the reactive center loop in the region
which contacts proteinase. Thus, despite the large size of serpin and serpin
proteinase complex, 45 and 69 kDa respectively, NMR provides a very sensitive
means of probing serpin conformation and mobility, which should be applicable
both to noncovalent and to covalent complexes with a range of different
proteinases, and probably to other serpins.
PMID- 11009601
TI - Structural effects of protein lipidation as revealed by LysB29-myristoyl,
des(B30) insulin.
AB - Intracellular proteins are frequently modified by covalent addition of lipid
moieties such as myristate. Although a functional role of protein lipidation is
implicated in diverse biological processes, only a few examples exist where the
structural basis for the phenomena is known. We employ the insulin molecule as a
model to evaluate the detailed structural effects induced by myristoylation.
Several lines of investigation are used to characterize the solution properties
of Lys(B29)(N(epsilon)-myristoyl) des(B30) insulin. The structure of the
polypeptide chains remains essentially unchanged by the modification. However,
the flexible positions taken up by the hydrocarbon chain selectively modify key
structural properties. In the insulin monomer, the myristoyl moiety binds in the
dimer interface and modulates protein-protein recognition events involved in
insulin dimer formation and receptor binding. Myristoylation also contributes
stability expressed as an 30% increase in the free energy of unfolding of the
protein. Addition of two Zn(2+)/hexamer and phenol results in the displacement of
the myristoyl moiety from the dimer interface and formation of stable R(6)
hexamers similar to those formed by human insulin. However, in its new position
on the surface of the hexamer, the fatty acid chain affects the equilibria of the
phenol-induced interconversions between the T(6), T(3)R(3), and R(6) allosteric
states of the insulin hexamer. We conclude that insulin is an attractive model
system for analyzing the diverse structural effects induced by lipidation of a
compact globular protein.
PMID- 11009603
TI - Comparison of the membrane interaction and permeabilization by the designed
peptide Ac-MB21-NH2 and truncated dermaseptin S3.
AB - Ac-MB21-NH(2) (Ac-FASLLGKALKALAKQ-NH(2)) and dermaseptin S3(1-16)-NH(2)
(ALWKNMLKGIGKLAGK-NH(2)) are cationic amphipathic peptides with antimicrobial
activity against a broad spectrum of microorganisms including various fungi. The
interaction of the peptides with liposomes was studied by exploiting the
tryptophan fluorescence of F1W-Ac-MB21-NH(2) and dermaseptin S3(1-16)-NH(2).
Spectral analysis and the use of quenchers indicate that the tryptophans of both
peptides insert more deeply in anionic than in zwitterionic liposomes. Membrane
insertion correlates with the formation of an alpha-helical peptide structure.
Both peptides permeabilize liposomes composed of anionic, cylindric phospholipids
more efficiently than liposomes formed of zwitterionic, conic (phospho)lipids.
PMID- 11009602
TI - Drug binding sites on P-glycoprotein are altered by ATP binding prior to
nucleotide hydrolysis.
AB - P-glycoprotein (P-gp) confers multiple drug resistance on cancer cells by acting
as a plasma membrane localized ATP-dependent drug efflux pump. Currently, there
is little information on the nature of the communication between the energy
providing nucleotide binding domains (NBDs) and the drug binding sites of P-gp to
generate transport of substrate. Many substrates and modulators cause alterations
in ATP hydrolysis, but what effect do the various stages of the catalytic cycle
have on drug interaction with P-gp? Vanadate trapping of Mg.ADP caused a
reversible decrease in the binding capacity of the transported substrate [(3)H]
vinblastine and the nontransported modulator [(3)H]XR9576 to P-gp in CH(r)B30
cell membranes. The non-hydrolyzable nucleotide analogue ATP-gamma-S also caused
a reduction in the binding capacity of [(3)H]-vinblastine but not for the
modulator [(3)H]XR9576. This indicates that signaling to the NBDs following
binding of a nontransported modulator is different to that transmitted upon
interaction of a transported substrate. Second, it appears that the binding of
nucleotide, rather than its hydrolysis, causes the initial conformational shift
in the drug-binding site during a transport cycle.
PMID- 11009604
TI - Actomyosin regulatory properties of yeast tropomyosin are dependent upon N
terminal modification.
AB - The yeast tropomyosin 1 gene (TPM1) encodes the major isoform of the two
tropomyosins (Tm) found in yeast. The gene has been expressed in E. coli and the
protein purified. The gene product (yTm1) is a 199-amino acid protein that has a
low affinity for actin compared to the native yTm1 purified from yeast. Mass
spectrometry shows that the native protein is acetylated while the recombinant
protein is not. A series of yTm1 N-terminal constructs were made with either an
Ala-Ser dipeptide extension previously shown to restore actin binding to skeletal
muscle Tm or the natural extension found in fibroblast Tm 5a/b. All constructs
bound actin tightly and showed similar CD spectra and thermal stability. All
constructs induced cooperativity in the equilibrium binding of myosin subfragment
1, to actin but the binding curves differed significantly between the constructs.
The apparent cooperative unit size (n) and closed/open equilibrium (K(T)) were
determined using a fluorescence titration technique [Maytum et al. (1998)
Biophys. J. 74, A347]. The data could be accounted for by changes in K(T) (0.1-1)
with no change in n. Values of n were approximately twice the structural unit
size (5 actin sites). The presence of yTm on actin had little effect upon the
overall affinity of S1 for actin despite showing an ability to regulate the acto
myosin interaction. These results show that the short yTm can aid our
understanding of actomyosin regulation and that the N-terminus of Tm has a major
influence upon its regulatory properties.
PMID- 11009605
TI - Investigation of the role of glutamine-471 and glutamine-1114 in the two
catalytic sites of P-glycoprotein.
AB - P-glycoprotein, also known as multidrug resistance protein, pumps drugs out of
cells using ATP hydrolysis as the energy source. Glutamine-471 and the
corresponding glutamine-1114 in the two catalytic sites of P-glycoprotein are
conserved in ABC transporters. X-ray structures show that they lie close to the
bound nucleotide. Proposed functional roles are (1) activation of the attacking
water for ATP hydrolysis, (2) coordination of the essential Mg(2+) cofactor in Mg
nucleotide, and (3) signal communication between catalytic site reaction
chemistry and drug-binding sites. We made mutations Q471A, Q471E, Q1114A, and
Q1114E in mouse MDR3 P-glycoprotein. Pure mutant and wild-type proteins were
prepared and subjected to enzymatic and biochemical characterization. We conclude
from the results that the primary role of this glutamine residue is in
interdomain signal communication. Coordination of the Mg(2+) cofactor is not a
critical functional role, neither is activation of the attacking water molecule,
although an auxiliary role in positioning the water cannot be ruled out. We found
that equivalent mutations (Ala or Glu) in either of the two P-glycoprotein
catalytic sites produced the same effects, implying functional symmetry of the
two sites.
PMID- 11009606
TI - (R)-3-hydroxybutyrate dehydrogenase: selective phosphatidylcholine binding by the
C-terminal domain.
AB - (R)-3-Hydroxybutyrate dehydrogenase (BDH) is a lipid-requiring mitochondrial
enzyme that has a specific requirement of phosphatidylcholine (PC) for function.
The C-terminal domain (CTBDH) of human heart BDH (residues 195-297) has now been
expressed in Escherichia coli as a chimera with a soluble protein, glutathione S
transferase (GST), yielding GST-CTBDH, a novel fusion protein that has been
purified and shown to selectively bind to PC vesicles. Both recombinant human
heart BDH (HH-Histag-BDH) and GST-CTBDH (but not GST) form well-defined protein
lipid complexes with either PC or phosphatidylethanolamine
(PE)/diphosphatidylglycerol (DPG) vesicles (but not with digalactosyl diglyceride
vesicles) as demonstrated by flotation in sucrose gradients. The protein-PC
complexes are stable to 0.5 M NaCl, but complexes of either HH-Histag-BDH or GST
CTBDH with PE/DPG vesicles are dissociated by salt treatment. Thrombin cleavage
of GST-CTBDH, either before or after reconstitution with PC vesicles, yields
CTBDH (12 111 Da by MALDI mass spectrometry) which retains lipid binding without
attached GST. The BDH activator, 1-palmitoyl-2-(1-pyrenyl)decanoyl-PC (pyrenyl
PC), at <2.5% of total phospholipid in vesicles, efficiently quenches a fraction
(0.36 and 0.47, respectively) of the tryptophan fluorescence of both HH-Histag
BDH and GST-CTBDH with effective Stern-Volmer quenching constants, (K(Q))(eff),
of 11 and 9.3 (%)(-)(1), respectively (half-maximal quenching at approximately
0.1% pyrenyl-PC). Maximal quenching by pyrenyl-PC obtains at approximately
stoichiometric pyrenyl-PC to protein ratios, reflecting high-affinity interaction
of pyrenyl-PC with both HH-Histag-BDH and GST-CTBDH. The analogous pyrenyl-PE
effects a similar maximal quenching of tryptophan fluorescence for both proteins
but with approximately 15-fold lower (K(Q))(eff) (half-maximal quenching at
approximately 1.5% pyrenyl-PE) referable to nonspecific interaction of pyrenyl-PE
with HH-Histag-BDH or GST-CTBDH. Thus, the 103-residue CTBDH constitutes a PC
selective lipid binding domain of the PC-requiring BDH.
PMID- 11009607
TI - Fluoride effects along the reaction pathway of pyrophosphatase: evidence for a
second enzyme.pyrophosphate intermediate.
AB - The fluoride ion is a potent and specific inhibitor of cytoplasmic
pyrophosphatase (PPase). Fluoride action on yeast PPase during PP(i) hydrolysis
involves rapid and slow phases, the latter being only slowly reversible
[Smirnova, I. N., and Baykov, A. A. (1983) Biokhimiya 48, 1643-1653]. A similar
behavior is observed during yeast PPase catalyzed PP(i) synthesis. The amount of
enzyme.PP(i) complex formed from solution P(i) exhibits a rapid drop upon
addition of fluoride, followed, at pH 7.2, by a slow increase to nearly 100% of
the total enzyme. The slow reaction results in enzyme inactivation, which is not
immediately reversed by dilution. These data show that fluoride binds to an
enzyme.PP(i) intermediate during the slow phase and to an enzyme.P(i)
intermediate during the rapid phase of the inhibition. In Escherichia coli PPase,
the enzyme.PP(i) intermediate binds F(-) rapidly, explaining the lack of time
dependence in the inhibition of this enzyme. The enzyme.PP(i) intermediate formed
during PP(i) hydrolysis binds fluoride much faster (yeast PPase) or tighter (E.
coli PPase) than the similar complex existing at equilibrium with P(i). It is
concluded that PPase catalysis involves two enzyme.PP(i) intermediates, of which
only one (immediately following PP(i) addition and predominating at acidic pH)
can bind fluoride. Simulation experiments have indicated that interconversion of
the enzyme.PP(i) intermediates is a partially rate-limiting step in the direction
of hydrolysis and an exclusively rate-limiting step in the direction of
synthesis.
PMID- 11009608
TI - Characterization of the regiochemistry and cryptoregiochemistry of a
Caenorhabditis elegans fatty acid desaturase (FAT-1) expressed in Saccharomyces
cerevisiae.
AB - To characterize the fatty acid desaturase produced by the fat-1 gene from the
nematode Caenorhabditis elegans, the functional expression of this enzyme was
effected in the yeast Saccharomyces cerevisiae. The GC-MS analysis of desaturated
products derived from various fatty acids, including deuterium-labeled thia fatty
acids supplied to growing cultures of transformed yeast, has defined the
substrate requirements, regiochemistry, and cryptoregiochemistry of the enzyme.
The desaturase acts on substrates of 16-20 carbons with a preference for omega-6
fatty acids, and its regioselectivity was confirmed to be that of an omega-3
desaturase. (omega-x refers to a double bond or desaturation between carbons x
and x+1, counting from the methyl end of a fatty acid.) The primary deuterium
kinetic isotope effects (KIEs) at C-15 and C-16 of a C18 fatty acid analogue were
measured via competitive incubation experiments: While k(H)/k(D) at the omega-3
position was shown to be large (7.8 +/- 0.4), essentially no KIE at the omega-2
position was observed (k(H)/k(D) = 0.99 +/- 0.04). This result indicates that
omega-3 desaturation is initiated by an energetically difficult C-H bond cleavage
at the carbon closer to the carboxyl terminus. The results are discussed in the
context of a general model relating the structure and function of membrane-bound
fatty acid desaturases featuring differing regioselectivities.
PMID- 11009609
TI - Lysine 199 is the general acid in the NAD-malic enzyme reaction.
AB - Site-directed mutagenesis was used to change K199 in the Ascaris suum NAD-malic
enzyme to A and R and Y126 to F. The K199A mutant enzyme gives a 10(5)-fold
decrease in V and a 10(6)-fold decrease in V/K(malate) compared to the WT enzyme.
In addition, the ratio for partitioning of the oxalacetate intermediate toward
pyruvate and malate changes from a value of 0.4 for the WT enzyme to 1.6 for
K199A, and repeating the experiment with A-side NADD gives isotope effects of 3
and 1 for the WT and K199A mutant enzymes, respectively. The K199R mutant enzyme
gives only a factor of 10 decrease in V, and the pK for the general acid in this
mutant enzyme has increased from 9 for the WT enzyme to >10 for the K199R mutant
enzyme. Tritium exchange from solvent into pyruvate is catalyzed by the WT
enzyme, but not by the K199A mutant enzyme. The Y126F mutant enzyme gives a 10(3)
fold decrease in V. The oxalacetate partition ratio and isotope effect on
oxalacetate reduction for the Y126F mutant enzyme are identical, within error, to
those measured for the WT enzyme. Thus, Y126 is important to the overall
reaction, but its role at present is unclear. Data are consistent with K199
functioning as the general acid that protonates C3 of enolpyruvate to generate
the pyruvate product in the malic enzyme reaction.
PMID- 11009610
TI - Kinetic mechanism of human histone acetyltransferase P/CAF.
AB - Human transcriptional coactivator P/CAF (p300/CBP-associating factor) is a
histone acetyltransferase (HAT) and is a member of the GNAT (GCN5 related N
acetyltransferases) superfamily. P/CAF was originally identified by its ability
to activate transcription of a variety of genes through its interaction with
p300/CBP. Though Lys-14 of histone H3 appears to be the preferred substrate,
other nonhistone proteins can also serve as substrates for P/CAF. However, few
studies have addressed the catalytic and kinetic mechanisms of histone/protein
acetylation by P/CAF. In this study, we have systematically determined the
kinetic mechanism for P/CAF, identified the critical ionizations for
binding/catalysis, and established the rate-limiting step in turnover. This was
accomplished by a variety of approaches including pH-dependent activity
measurements, Bi-substrate kinetic analysis, authentic product inhibition by
coenzyme A (CoA) and acetylated H3 (Ac-Lys-14) peptide, direct measurements of
substrate/product binding affinities (equilibrium dialysis), and a pre-steady
state quench-flow analysis. The results are consistent with a fully ordered Bi-Bi
kinetic mechanism, where chemical catalysis is rate-determining. Acetyl-CoA
(AcCoA) binds with high affinity (K(d) = 0.64 +/- 0.12 microM) to the free form
of the enzyme. Histone H3 peptide binds (apparent K(d) = 116 +/- 17 microM) only
after AcCoA is bound. No H3 peptide binding to the free enzyme was detectable. In
the ternary complex, the epsilon-amino of Lys-14 (H3 peptide substrate) directly
attacks the carbonyl carbon of AcCoA, transferring the acetyl group to the
acceptor peptide substrate (rate-limiting step). Products are released in an
ordered fashion, with Ac-Lys-14 H3 released first followed by release of CoA. The
pH dependency of the k(cat)/K(m) parameter revealed two P/CAF ionizable groups
(pK(a) values of 6.9 and 7.5) that must be unprotonated for activity. The group
with a pK(a) value 7.5 was assigned to Glu-570, which is the proposed general
base catalyst, abstracting a proton from the epsilon-amino group and facilitating
nucleophilic attack.
PMID- 11009611
TI - 5' --> 3' molecular polarity of human replication protein A (hRPA) binding to
pseudo-origin DNA substrates.
AB - Human replication protein A (hRPA) was previously seen to efficiently bind a 48
bp simian virus 40 (SV40) "pseudo-origin" (PO) substrate that mimics a DNA
structure found within the SV40 T antigen-origin (ori) complex. To understand the
role of hRPA during the initiation of replication, we examined the PO sequence
and structure requirements for hRPA interaction. Binding and unwinding were found
to be most efficient when both strands of the central 8 nt single-stranded DNA
(ssDNA) bubble region contained a polypyrimidine structure, with these activities
proportionately reduced when the bubble region was replaced with a purine tract
on one or both strands. Examination of the importance of the two duplex flanks
indicates that the early gene side contains a DNA structural feature located one
duplex turn from the bubble whose mutation significantly affects the affinity of
hRPA for the substrate. When present in the context of ori, mutation of this
sequence was seen to have significant effects on SV40 DNA replication in vitro
and on the denaturation of ori, indicating that origin activity can be modulated
by cis-acting elements which alter the hRPA binding affinity. Use of fork and
overhang substrates containing 8 nt pyrimidine or purine arms demonstrates that
hRPA binding to DNA involves a particular molecular polarity in which initial
hRPA binding occurs on the 5' side of a ssDNA substrate, and then extends in the
3' direction to create a stably bound hRPA. These data have implications on the
mechanism of the initiation of eukaryotic DNA replication as well as on the sites
of nascent strand synthesis within the origin.
PMID- 11009612
TI - Cleavage of symmetric immobile DNA junctions by Escherichia coli RuvC.
AB - The Holliday junction is a key DNA intermediate in the process of genetic
recombination. It consists of two double-helical domains composed of homologous
strands that flank a branch point; two of the strands are roughly helical, and
two form the crossover between the helices. RuvC is a Holliday junction resolvase
that cleaves the helical strands at a symmetric sequence, leading to the
production of two recombinant molecules. We have determined the position of the
cleavage site relative to the crossover point by the use of symmetric immobile
junctions; these are DNA molecules containing two crossover points, one held
immobile by sequence asymmetry and the second a symmetric sequence, but held
immobile by torsional coupling to the first junction. We have built five
symmetric immobile junctions, in which the tetranucleotide recognition site is
moved stepwise relative to the branch point. We have used kinetic analysis of
catalysis, gel retardation, and hydroxyl radical hypersensitivity to analyze this
system. We conclude that the internucleotide linkage one position 3' to the
crossover point is the favored site of cleavage.
PMID- 11009613
TI - Interaction of the Escherichia coli replication terminator protein (Tus) with
DNA: a model derived from DNA-binding studies of mutant proteins by surface
plasmon resonance.
AB - The Escherichia coli replication terminator protein (Tus) binds tightly and
specifically to termination sites such as TerB in order to halt DNA replication.
To better understand the process of Tus-TerB interaction, an assay based on
surface plasmon resonance was developed to allow the determination of the
equilibrium dissociation constant of the complex (K(D)) and association and
dissocation rate constants for the interaction between Tus and various DNA
sequences, including TerB, single-stranded DNA, and two nonspecific sequences
that had no relationship to TerB. The effects of factors such as the KCl
concentration, the orientation and length of the DNA, and the presence of a
single-stranded tail on the binding were also examined. The K(D) measured for the
binding of wild type and His(6)-Tus to TerB was 0.5 nM in 250 mM KCl. Four
variants of Tus containing single-residue mutations were assayed for binding to
TerB and the nonspecific sequences. Three of these substitutions (K89A, R198A,
and Q250A) increased K(D) by 200-300-fold, whereas the A173T substitution
increased K(D) by 4000-fold. Only the R198A substitution had a significant effect
on binding to the nonspecific sequences. The kinetic and thermodynamic data
suggest a model for Tus binding to TerB which involves an ordered series of
events that include structural changes in the protein.
PMID- 11009614
TI - Amphipathic helices support function of blood coagulation factor IXa.
AB - Blood coagulation factor IXa gains proteolytic efficiency upon binding to a
phospholipid membrane. We have found that an amphipathic, membrane-binding
peptide from the C2 domain of factor VIII, fVIII(2303)(-23), enhances proteolytic
efficiency of factor IXa in the absence of phospholipid membranes. This
enhancement is the result of a reduction in the K(M) for the substrate, factor X,
with little effect on the k(cat). Enhanced function requires interaction of the
gamma-carboxyglutamic acid (Gla) domains of factor IXa and factor X since (i) a
synthetic peptide comprising the Gla domain of factor IXa and antibodies directed
to the Gla domain of factor IXa inhibit this acceleration, (ii) the acceleration
is Ca(II) dependent, and (iii) conversion of Gla-domainless factor X is not
affected by the presence of fVIII(2303)(-23). The effect of fVIII(2303)(-23) on
factor IXa parallels the enhanced function produced by phosphatidylserine
containing bilayers, and fVIII(2303)(-23) does not further enhance function of
factor IXa when phospholipid vesicles are present. The critical feature of
fVIII(2303)(-23) is apparently its amphipathic helix-forming structure [Gilbert,
G. E., and Baleja, J. D. (1995) Biochemistry 34, 3022-3031] because other alpha
helical peptides such as a homologous peptide from the C2 domain of factor V and
melittin have similar effects. Diastereomeric analogues of fVIII(2303)(-23) and
melittin, which have reduced helical content, do not support factor IXa activity.
A truncated peptide of fVIII(2303)(-23) with three C-terminal residues deleted
retains alpha-helical content but loses capacity to enhance factor X cleavage,
suggesting that a minimum length of alpha-helix is required. Although these
results probably do not illuminate the physiologic function of the factor VIII
peptide corresponding to fVIII(2303)(-23), they demonstrate a novel, membrane
mimetic role of amphipathic helical peptides in supporting function of factor
IXa.
PMID- 11009615
TI - Novel inactivation of enoyl-CoA hydratase via beta-elimination of 5, 6-dichloro
7,7,7-trifluoro-4-thia-5-heptenoyl-CoA.
AB - 5,6-Dichloro-7,7,7-trifluoro-4-thia-5-heptenoyl-CoA (DCTFTH-CoA) is an analogue
of a class of cytotoxic 4-thiaacyl-CoA thioesters that can undergo a beta
elimination reaction to form highly unstable thiolate fragments, which yield
electrophilic thioketene or thionoacyl halide species. Previous work demonstrated
that the medium-chain acyl-CoA dehydrogenase both bioactivates and is inhibited
by these CoA thioesters through enzyme-catalyzed beta-elimination of the reactive
thiolate moiety [Baker-Malcolm, J. F., Haeffner-Gormley, L., Wang, L., Anders, M.
W., and Thorpe, C. (1998) Biochemistry 37, 1383-1393]. This paper shows that
DCTFTH-CoA can be directly bioactivated by the enoyl-CoA hydratase (ECH) with the
release of 1,2-dichloro-3,3,3-trifluoro-1-propenethiolate and acryloyl-CoA. In
the absence of competing exogenous trapping agents, DCTFTH-CoA effects rapid and
irreversible loss of hydratase activity. The inactivator is particularly
effective at pH 9.0, with a stoichiometry approaching 1 mol of DCTFTH-CoA per
enzyme subunit. Modification is associated with a new protein-bound chromophore
at 360 nm and an increase in mass of 89 +/- 5 per subunit. Surprisingly, ECH
exhibiting less than 2% residual hydratase activity retains essentially 100% beta
eliminase activity and continues to generate reactive thiolate species from
DCTFTH-CoA. This leads to progressive derivatization of the enzyme with
additional UV absorbance, covalent cross-linking of subunits, and an eventual
complete loss of beta-eliminase activity. A range of exogenous trapping agents,
including small thiol nucleophiles, various proteins, and even phospholipid
bilayers, exert strong protection against modification of ECH. Peptide mapping,
thiol titrations, UV-vis spectrophotometry, and mass spectrometry show that
inactivation involves the covalent modification of Cys62 and/or Cys111 of the
recombinant rat liver ECH. These data suggest that enoyl-CoA hydratase is an
important enzyme in the bioactivation of DCTFTH-CoA, in a pathway which does not
require involvement of the medium-chain acyl-CoA dehydrogenase.
PMID- 11009616
TI - Basis for half-of-the-site reactivity and the dominance of the K487 oriental
subunit over the E487 subunit in heterotetrameric human liver mitochondrial
aldehyde dehydrogenase.
AB - Human liver mitochondrial aldehyde dehydrogenase is a tetrameric enzyme composed
of 4 identical 500 amino acid containing subunits arranged such that the protein
is a dimer of dimers. No kinetic evidence for subunit interactions has been
reported. However, the enzyme exhibits half-of-the-site reactivity in that there
is a pre-steady-state burst of 2 mol of NADH per mole of enzyme. A variant of the
enzyme, found in Asian people, contains a lysine rather than a glutamate at
position 487. This enzyme has a high K(M) for NAD(+) and a low specific activity.
In heterotetramers composed of both subunit types, it appeared that the lysine
containing subunit was dominant over the glutamate-containing subunits. To allow
for the separation of various heterotetrameric forms of the enzyme, surface
residues were changed. Each of the five possible tetrameric forms of the modified
enzyme was isolated and characterized with respect to steady-state kinetics and
pre-steady-state burst magnitudes. The data best fit a model where in each dimer
pair there is one functioning and one nonfunctioning subunit. Further, the lysine
subunit affects the properties only of its dimer partner. Residue 487 is located
at the dimer interface, and the glutamate forms salt bonds with two arginine
residues. One is to Arg(264) in the same subunit; the other is to Arg(475)
located in the other subunit. Most likely the presence of a lysine affects these
salt bonds so the lysine subunit can cause the other subunit to become
essentially nonfunctional.
PMID- 11009617
TI - Folding of green fluorescent protein and the cycle3 mutant.
AB - Although the correct folding of green fluorescent protein (GFP) is required for
formation of the chromophore, it is known that wild-type GFP cannot mature
efficiently in vivo in Escherichia coli at 37 degrees C or higher temperatures
that the jellyfish in the Pacific Northwest have never experienced. Recently, by
random mutagenesis by the polymerase chain reaction (PCR) method, a mutant called
Cycle3 was constructed. This mutant had three mutations, F99S, M153T, and V163A,
on or near the surface of the GFP molecule and was able to mature correctly even
at 37 degrees C [Crameri et al. (1996) Nat. Biotechnol. 143, 315-319]. In the
present study, we investigated the differences in their folding behavior in
vitro. We observed the folding and unfolding reactions of both wild-type GFP and
the Cycle3 mutant by using green fluorescence as an indicator of the formation of
the native structure and examining hydrogen-exchange reactions by Fourier
transform infrared spectroscopy. Both proteins showed unusually slow refolding
and unfolding rates, and their refolding rates were almost identical under the
native state at 25 and at 35 degrees C. On the other hand, aggregation studies in
vitro showed that wild-type GFP had a strong tendency to aggregate, while the
Cycle3 mutant did not. These results indicated that the ability to mature
efficiently in vivo at 37 degrees C was not due to the improved folding and that
reduced hydrophobicity on the surface of the Cycle3 mutant was a more critical
factor for efficient maturation in vivo.
PMID- 11009618
TI - Contribution of individual disulfide bonds to the oxidative folding of
ribonuclease A.
AB - The eight cysteine residues of ribonuclease A form four disulfide bonds in the
native protein. We have analyzed the folding of three double RNase A mutants
(C65A/C72A, C58A/C110A, and C26A/C84A, lacking the C65-C72, C58-C110, and C26-C84
disulfide bonds, respectively) and two single mutants (C110A and C26A), in which
a single cysteine is replaced with an alanine and the paired cysteine is present
in the reduced form. The folding of these mutants was carried out in the presence
of oxidized and reduced glutathione, which constitute the main redox agents
present within the ER. The use of mass spectrometry in the analysis of the
folding processes allowed us (i) to follow the formation of intermediates and
thus the pathway of folding of the RNase A mutants, (ii) to quantitate the
intermediates that formed, and (iii) to compare the rates of formation of
intermediates. By comparison of the folding kinetics of the mutants with that of
wild-type RNase A, the contribution of each disulfide bond to the folding process
has been evaluated. In particular, we have found that the folding of the
C65A/C72A mutant occurs on the same time scale as that of the wild-type protein,
thus suggesting that the removal of the C65-C72 disulfide bond has no effect on
the kinetics of RNase A folding. Conversely, the C58A/C110A and C26A/C84A mutants
fold much more slowly than the wild-type protein. The removal of the C58-C110 and
C26-C84 disulfide bonds has a dramatic effect on the kinetics of RNase A folding.
Results described in this paper provide specific information about conformational
folding events in the regions involving the mutated cysteine residues, thus
contributing to a better understanding of the complex mechanism of oxidative
folding.
PMID- 11009619
TI - Phosphoisoprenoid binding specificity of geranylgeranyltransferase type II.
AB - Geranylgeranyltransferase type II (GGTase-II) modifies small monomeric GTPases of
the Rab family by attaching geranylgeranyl moieties onto two cysteines of their C
terminus. We investigated to what extent GGTase-II discriminates between its
native substrate geranylgeranyl pyrophosphate (GGpp) and other
phosphoisoprenoids, including farnesyl pyrophosphate (Fpp). On the basis of a
novel fluorescent assay, we demonstrated that GGpp binds to GGTase-II with an
affinity of 8 +/- 4 nM, while Fpp is bound less strongly (K(d) = 60 +/- 8 nM).
Analysis of the binding kinetics of four different phosphoisoprenoids indicated
that in all cases association is rapid, with rate constants in the range of 0.15
nM(-1) s(-1). In contrast, the dissociation rates differed greatly, depending on
the phosphoisoprenoid used, with weak binding substrates generally displaying an
increased rate of dissociation. The affinity of GGpp and Fpp for GGTase-II was
also determined in the presence of the Rab7-REP-1 complex. The affinity for GGpp
was essentially unaffected by the presence of the complex; Fpp on the other hand
bound less strongly to the GGTase-II under these conditions, resulting in a K(d)
of 260 +/- 60 nM. In vitro prenylation experiments were used to establish that
Fpp not only does bind to GGTase-II but also is transferred with an observed rate
constant of 0.082 s(-1) which is very similar to that of GGpp. The implications
of the low level of discrimination by GGTase-II for the in vivo specificity of
the enzyme and the use of farnesyltransferase inhibitors in anti-cancer therapy
are discussed.
PMID- 11009620
TI - Vinca alkaloid-induced tubulin spiral formation correlates with cytotoxicity in
the leukemic L1210 cell line.
AB - The ability of a class of C-20' modified vinca alkaloid congeners to induce
tubulin spiral formation was investigated relative to their ability to inhibit
microtubule assembly, their cytotoxicity against a leukemic cell line, L1210, and
their measured and calculated partition coefficients. These studies were prompted
by the observation that the energetics of vinca alkaloid-induced tubulin spiral
polymers, or spiraling potential, is inversely related to their clinical dosage
and are aimed at the long-term goal of developing the ability to predict the
cytotoxic and antineoplastic properties of antimitotic drugs. We demonstrate here
that vinca-induced tubulin-spiraling potential is significantly correlated with
cytotoxicity against L1210 cells. This is consistent with the size of spirals
formed being proportional to the relaxation time for polymer redistribution, the
lifetime of cell retention, and effects on microtubule ends and dynamics.
Spiraling potential also correlates with calculated but not measured partition
coefficients. Surprisingly, spiraling potential does not correlate with the
ability to inhibit microtubule formation with purified tubulin or microtubule
protein. For the set of C-20' modified compounds studied, the largest inhibitory
effects on spiraling potential and cytotoxicity are caused by multiple sites of
halogen (-F, -Cl) substitution with the introduction of increased rigidity in the
ring. This suggests the C-20' position interacts with a hydrogen bond acceptor or
an electrophilic region on the protein that electrostatically disfavors halogen
substitutions. These studies are discussed in terms of the cellular mode of
action of antimitotic drugs, particularly the importance of microtubule dynamics
during mitosis and the factors that regulate those dynamics.
PMID- 11009621
TI - Pressure effect on the conformational fluctuation of apomyoglobin in the native
state.
AB - We have investigated the effect of pressure on fluctuations of the native state
of sperm whale apomyoglobin (apoMb) by H/D exchange, fluorescence, and limited
proteolysis. The results from intrinsic fluorescence showed that a large fraction
of apoMb molecules is in the native conformation in the pressure range from 0.1
to 150 MPa at 293 K and pH 6.0. The H/D exchange of protons of the individual
backbone amino acids in this pressure range was monitored by NMR. The rate of H/D
exchange was enhanced at high pressure, with the protection factors for some
residues decreasing by factors of more than 100 compared to the values at 0.1
MPa. The amplitude of the decrease of the protection factor varied among the
individual amino acids on the same secondary structure unit. This result suggests
that H/D exchange in apoMb is explained best by the penetration model, in which
solvent penetrates into the protein matrix via small motions. The result from
limited proteolysis under high pressure showed that a pressure increase does not
induce local unfolding of the secondary structure units of apoMb. Conformational
fluctuations much smaller than local unfolding evidently provide pathways for
water to diffuse into the protein interior, and are enhanced by an increase of
pressure.
PMID- 11009622
TI - Isotope effects in the transient phases of the reaction catalyzed by ethanolamine
ammonia-lyase: determination of the number of exchangeable hydrogens in the
enzyme-cofactor complex.
AB - Transient phases of the reaction catalyzed by ethanolamine ammonia-lyase (EAL)
from Salmonella typhimurium have been investigated by stopped-flow visible
spectrophotometry and deuterium kinetic isotope effects. The cleavage of
adenosylcobalamin (coenzyme B(12)) to form cob(II)alamin (B(12r)) with
ethanolamine as the substrate occurred within the dead time of the instrument
whenever coenzyme B(12) was preincubated with enzyme prior to mixing with
substrate. The rate was, however, slowed sufficiently to be measured with
perdeutero ethanolamine as the substrate. Optical spectra indicate that, during
the steady states of the reactions with ethanolamine and with S-2-aminopropanol
as substrates, approximately 90% of the active sites contain B(12r). Reformation
of the carbon-cobalt bond of the cofactor occurs following depletion of substrate
in the reaction mixtures, and the rate constant for this process reflects k(cat)
of the respective substrates. This late phase of the reaction also exhibits (2)H
isotope effects similar to those measured for the overall reaction with (2)H
labeled substrates. With unlabeled substrates, the rate of cofactor reassembly is
independent of the number of substrate molecules turned over in the steady-state
phase. However, with (2)H-labeled substrates, kinetic isotope effects appear in
the reassembly phase, and these isotope effects are maximal after only
approximately 2 equiv of substrate/active site are processed. With 5'-deuterated
coenzyme B(12) and deuterated substrate, the isotope effect on reassembly is
independent of the number of substrate molecules that are turned over. These
results indicate that the pool of exchangeable hydrogens in the enzyme-cofactor
complex is two-a finding consistent with the hydrogens in the C5' methylene of
coenzyme B(12).
PMID- 11009623
TI - Structural effects of O-glycosylation on a 15-residue peptide from the mucin
(MUC1) core protein.
AB - To study the effect of O-glycosylation on the conformational propensities of a
peptide backbone, the 15-residue peptide PPAHGVTSAPDTRPA (PPA15) from the MUC1
protein core and its analogue PPA15(T7), glycosylated with alpha-N
acetylgalactosamine on Thr7, were prepared and investigated by NMR spectroscopy.
The peptide contains both the GVTSAP sequence, which is an effective substrate
for GalNAc-T1 and -T3 transferases, and the PDTRP fragment, which is a well-known
immunodominant epitope recognized by several anti-MUC1 monoclonal antibodies.
Useful structural results were obtained in water upon decreasing the temperature
to 5-10 degrees C. The sugar attachment slightly affected the conformational
equilibrium of the peptide backbone near the glycosylated Thr7 residue. The
clustering of low-energy conformations for both PPA15 and PPA15(T7) within the
GVTSAP and APDTRP fragments revealed structural similarities between glycosylated
and nonglycosylated peptides. For the GVTSAP region, minor but distinct clusters
formed by either PPA15 or PPA15(T7) conformers showed distinct structural
propensities of the peptide backbone specific for either the nonglycosylated or
the glycosylated peptide. The peptide backbone of the APDTRP fragment, which is a
well-known immunodominant region, resembled an S-shaped bend. A similar
structural motif was found in the GVTSAP fragment. The S-shaped structure of the
peptide backbone is formed by consecutive inverse gamma-turn conformations
partially stabilized by hydrogen bonding. A comparison of the solution structure
of the APDTRP fragment with a crystal structure of the MUC1 peptide antigen bound
to the breast tumor-specific antibody SM3 demonstrated significant structural
similarities in the general shape.
PMID- 11009624
TI - Calcium enhances heparin catalysis of the antithrombin-factor Xa reaction by
promoting the assembly of an intermediate heparin-antithrombin-factor Xa bridging
complex. Demonstration by rapid kinetics studies.
AB - Heparin catalyzes the inhibition of factor Xa by antithrombin mainly through an
allosteric activation of the serpin inhibitor, but an alternative heparin
bridging mechanism has been suggested to enhance the catalysis in the presence of
physiologic calcium levels due to calcium interactions with the Gla domain
exposing a heparin binding exosite in factor Xa. To provide direct evidence for
this bridging mechanism, we studied the heparin-catalyzed reaction of
antithrombin with factor Xa, Gla-domainless factor Xa (GDFXa), and a heparin
binding exosite mutant of GDFXa in the absence and presence of calcium using
rapid kinetic methods. The pseudo-first-order rate constant for factor Xa
inhibition by antithrombin complexed with a long-chain approximately 70
saccharide heparin showed a saturable dependence on inhibitor concentration in
the presence but not in the absence of 2.5 mM Ca(2+), indicating the formation of
an intermediate heparin-serpin-proteinase encounter complex with a dissociation
constant of approximately 90 nM prior to formation of the stable serpin
proteinase complex with a rate constant of approximately 20 s(-1). Similar
saturation kinetics were observed for the inhibition of GDFXa by the antithrombin
heparin complex, except that Ca(2+) was not required for the effect. By contrast,
no Ca(2+)-dependent saturation of the inhibition rate constant was detectable
over the same range of inhibitor concentrations for reactions of either a short
chain approximately 26-saccharide high-affinity heparin-antithrombin complex with
factor Xa or the long-chain heparin-antithrombin complex with the heparin binding
exosite mutant, GDFXa R240A. These findings suggest that binding of full-length
heparin chains to an exosite of factor Xa in the presence of Ca(2+) produces a
chain-length-dependent lowering of the dissociation constant for assembly of the
intermediate heparin-antithrombin-factor Xa encounter complex, resulting in a
several 100-fold rate enhancement by a heparin bridging mechanism.
PMID- 11009625
TI - Effects of compound structure on carbazole dication-DNA complexes: tests of the
minor-groove complex models.
AB - Carbazole dications have shown excellent activity against opportunistic
infections, but they are quite different in structure from previously studied
unfused aromatic cations that function by targeting the DNA minor groove. In a
previous report [Tanious, F. A., Ding, D., Patrick, D. A., Tidwell, R. R., and
Wilson, W. D. (1997) Biochemistry 36, 15315-15325] we showed that, despite their
fused ring structure, the carbazoles also bind in A/T sequences of the DNA minor
groove and we proposed models for the carbazole-DNA complexes with the carbazole
nitrogen facing out of the groove for 3,6 substituted compounds but into the
groove in 2,7 carbazoles. To test and refine the models, carbazole-N-methyl
substituted derivatives have been synthesized in both the 3,6 and 2,7 series as
well as a new 2,6 substituted NH derivative that is intermediate in structure.
Footprinting results indicate a broad AT specificity of carbazole binding and a
pattern in agreement with a minor groove complex. Surface plasmon resonance
biosensor analysis of carbazole binding to an oligomer with an AATT central
sequence indicated that the 2,7 NH compound has the largest binding constant.
Both the 3,6 NH and NMe compounds bind with similar equilibrium constants that
are less than for the 2,7 NH compound. The 2,7 NMe compound has the lowest
binding constant of all the carbazoles. Spectroscopic results are also similar
for the two 3,6 derivatives but are quite different for the 2,7 NH and NMe
carbazole dications. Structural analysis of carbazole complexes with an AATT
sequence by 2D NMR methods also supported a minor groove complex of the
carbazoles in orientations in agreement with the previously proposed models. From
these results, it is clear that the fused ring carbazoles can bind strongly in
the DNA minor groove with a broad A/T specificity and that the 2,7 and 3,6
substituted carbazoles bind to the minor groove in opposite orientations.
PMID- 11009626
TI - Intramolecular activation of a Ca(2+)-dependent protein kinase is disrupted by
insertions in the tether that connects the calmodulin-like domain to the kinase
PMID- 11009627
TI - A computer model of normal conduction in the human atria.
AB - Although considerable progress has been made in understanding the process of
wavefront propagation and arrhythmogenesis in human atria, technical concerns and
issues of patient safety have limited experimental investigations. The present
work describes a finite volume-based computer model of human atrial activation
and current flow to complement these studies. Unlike previous representations,
the model is three-dimensional, incorporating both the left and right atria and
the major muscle bundles of the atria, including the crista terminalis, pectinate
muscles, limbus of the fossa ovalis, and Bachmann's bundle. The bundles are
represented as anisotropic structures with fiber directions aligned with the
bundle axes. Conductivities are assigned to the model to give realistic local
conduction velocities within the bundles and bulk tissue. Results from
simulations demonstrate the role of the bundles in a normal sinus rhythm and also
reveal the patterns of activation in the septum, where experimental mapping has
been extremely challenging. To validate the model, the simulated normal
activation sequence and conduction velocities at various locations are compared
with experimental observations and data. The model is also used to investigate
paced activation, and a mechanism of the relative lengthening of left versus
right stimulation is presented. Owing to both the realistic geometry and the
bundle structures, the model can be used for further analysis of the normal
activation sequence and to examine abnormal conduction, including flutter. The
full text of this article is available at http://www.circresaha.org.
PMID- 11009628
TI - Long-distance learning.
PMID- 11009629
TI - Patient rights reach Capitol Hill.
PMID- 11009630
TI - Compliance efforts get some PEPP.
PMID- 11009631
TI - CPR systems: which one is right for your organization?
PMID- 11009632
TI - Next generation: how Internet technology propels the electronic medical record.
PMID- 11009633
TI - Beyond Y2K: no rest for the weary.
PMID- 11009634
TI - Tools for defining data.
PMID- 11009635
TI - PPS + new technology = growing pains.
PMID- 11009636
TI - Reimbursement at your fingertips--a glossary of terms.
PMID- 11009637
TI - Practice brief. Correcting and amending entries in a computerized patient record.
American Health Information Management Association.
PMID- 11009638
TI - Breaking with tradition: improving HIM functions in behavioral health.
PMID- 11009639
TI - Using electronic resources to recruit and hire employees.
PMID- 11009640
TI - Getting ready for APCs.
PMID- 11009641
TI - Summary of ICD-9-CM Coordination and Maintenance Committee meeting.
AB - The ICD-9-CM Coordination and Maintenance Committee, cosponsored by the National
Center for Health Statistics (NCHS) and the Health Care Financing Administration
(HCFA), recently met in Baltimore, MD. Donna Pickett, RRA (NCHS), and Patricia
Brooks, RRA (HCFA), cochaired the meeting. Proposed modifications to ICD-9-CM
were presented and are summarized below. Unless otherwise indicated, the audience
generally supported the proposed changes.
PMID- 11009642
TI - Charting new territory.
PMID- 11009643
TI - HSS proposes HIPAA privacy standards.
PMID- 11009644
TI - Using CPT modifier -25 for professional billing.
PMID- 11009645
TI - E-commerce and HIM: ready or not, here it comes.
PMID- 11009646
TI - A crystal ball for coding.
PMID- 11009647
TI - XML: defining the transition from paper to digital records.
PMID- 11009648
TI - Trend watch: coding for nonphysician services.
PMID- 11009649
TI - Coders join forces with physicians to improve clinical outcomes.
PMID- 11009650
TI - An off-site coding success story.
PMID- 11009651
TI - Ten down under: implementing ICD-10 in Australia.
PMID- 11009652
TI - A global language for pharmaceutical regulation.
PMID- 11009653
TI - Practice brief. Information security: a checklist for healthcare professionals
(updated). American Health Information Management Association.
PMID- 11009654
TI - When you don't see eye to eye with a Joint Commission surveyor.
PMID- 11009655
TI - Using scenario planning.
PMID- 11009656
TI - CPT changes for 2000.
PMID- 11009657
TI - Incentive programs offer aid to increase coding productivity.
PMID- 11009658
TI - American Health Information Management Association. Standards of ethical coding.
PMID- 11009659
TI - Ensuring compliance in the new frontier.
PMID- 11009660
TI - AHIMA comments on privacy rule.
PMID- 11009661
TI - Medical and clinical service contracts: a compliance focus.
PMID- 11009662
TI - Web-based patient record systems: opportunities for best practices.
PMID- 11009663
TI - For health records on the Internet, the future is now.
PMID- 11009664
TI - Online consumer health records: revolution or confusion?
PMID- 11009665
TI - PCASSO: a model for safe use of the Internet in healthcare.
PMID- 11009666
TI - Intranets: a way to connect.
PMID- 11009667
TI - "Pointing and clicking" your way to knowledge.
PMID- 11009668
TI - Web-based education cuts training time, saves money.
PMID- 11009669
TI - Patient-centered e-mail: developing the right policies.
PMID- 11009670
TI - Simplified deficiency processing brings hospital-wide benefits.
PMID- 11009671
TI - Resolving confidentiality barriers in research data collection.
PMID- 11009672
TI - Professional practice solutions ... hospital scheduled to be surveyed this year
by the Joint Commission.
PMID- 11009673
TI - Post-acute markets face Medicare, HCFA changes.
PMID- 11009674
TI - Practice brief. Authentication of health record entries (updated). American
Healthcare Information Management Association.
PMID- 11009675
TI - Hiring the best: testing applicants.
PMID- 11009676
TI - Committee proposes ICD-9-CM changes for 2001.
PMID- 11009677
TI - Reviewing the details of coding septicemia.
PMID- 11009678
TI - IOM report examines medical errors.
PMID- 11009679
TI - HIPAA: understanding the requirements.
PMID- 11009680
TI - Taking the lead in compliance education.
PMID- 11009681
TI - Are we ready for portable healthcare?
PMID- 11009682
TI - HIPAA: where to begin? Next steps? First steps? Getting a grip on HIPAA security
standards. Panel discussion.
PMID- 11009683
TI - Getting ready for HIPAA privacy rules.
PMID- 11009684
TI - Health informatics standards: a user's guide.
PMID- 11009685
TI - Long-term care's prospects for accreditation.
PMID- 11009686
TI - To "e" or not to "e": HIM and the dawn of e-health.
PMID- 11009687
TI - MPIs (master patient index) in healthcare: current trends and practices.
PMID- 11009688
TI - Boosting efficiency in home health record systems.
PMID- 11009689
TI - Practice brief. Destruction of patient health information (updated). American
Health Information Management Association.
PMID- 11009690
TI - Guidelines for a "win-win" vendor relationship.
PMID- 11009691
TI - Clarifying selected CPT modifiers.
AB - This discussion includes only 20 percent of the modifiers available for physician
reporting, but could account for 80 percent of modifiers assigned for physician
services. Modifier -91 was the only new modifier introduced in CPT 2000 and it is
used to report a repeat clinical diagnostic laboratory test. It is not to be used
when confirming initial results or for any other reason other than a clinical
need to repeat the test for the same patient on the same day. Success with CPT
modifier reporting requires a thorough review of CPT guidelines and some
detective work for identifying health plan requirements for modified codes.
PMID- 11009692
TI - Modifier usage for hospital outpatient services.
PMID- 11009693
TI - Setting the standards.
PMID- 11009694
TI - Blueprint for a 21st century hospital: a casebook in strategic and operational
planning.
PMID- 11009695
TI - Why patients complain and what health professionals can do about it.
PMID- 11009696
TI - Reducing medication errors. Part II: Newton-Wellesley Hospital, Newton, MA.
PMID- 11009697
TI - Gearing up for the JCAHO's new pain management standards: some hospitals are
ahead of the game.
PMID- 11009698
TI - Grassroots decisionmaking informs care redesign at York Hospital in York, PA.
PMID- 11009699
TI - Katie's crusade. Colon cancer is one of the deadliest and most preventable
malignancies. What you need to know about the disease--and the surprisingly
painless test that could save your life.
PMID- 11009700
TI - Spare a kidney? You don't have to be dead to donate an organ, but you had better
know the risks before you give it up.
PMID- 11009702
TI - A pencil in his heart. Nathan king is alive today because his mother was level
headed enough not to try to pull it out.
PMID- 11009703
TI - Smoke screen. Kids are less likely to use tobacco if they're shown how cigarette
companies try to dupe them.
PMID- 11009701
TI - When pills make sense. Some parents turn too quickly to mood-altering drugs. But
often medication is the right choice.
PMID- 11009704
TI - The dizzy mystery. Dizzy spells are a natural consequence of aging, but they can
also mean that something is wrong.
PMID- 11009705
TI - Affair of the heart. A new study finds that estrogen may not protect women
against cardiac disease. Here's why.
PMID- 11009706
TI - Cloning the new babes. Science comes closer to creating the perfect pig, offering
hope for a larder of rejection-free organs.
PMID- 11009708
TI - A biotech wreck. It's an industry full of Ps--promises and potential. Call me
when they get to profits.
PMID- 11009707
TI - The Web docs. The Internet can fill the gaps in your medical knowledge. But you
need to know how to separate the good sites from the bad.
PMID- 11009709
TI - Diabetes recall. Though Rezulin's withdrawal is a blow for some patients, there
are ways to cope. Here's how.
PMID- 11009710
TI - Cutting stealth flab. That winter baggage may be less than you thought. Still,
it's spring, so here's how to lose it.
PMID- 11009711
TI - The Feds step up the pace. In the hot race to wrap up the human genome,
government mappers say they're two-thirds home.
PMID- 11009712
TI - Unkindest cut? Most moms don't need a minor surgery to deliver.
PMID- 11009713
TI - Will the mind figure out how the brain works?
PMID- 11009714
TI - Will we figure out how life began?
PMID- 11009716
TI - Will we keep evolving?
PMID- 11009715
TI - Will we clone a dinosaur?
PMID- 11009717
TI - The race is over. The great genome quest is officially a tie, thanks to a round
of pizza diplomacy. Yet lead researcher Craig Venter still draws few cheers from
his colleagues.
PMID- 11009718
TI - The genome is mapped. Now what? It will be decades before scientists identify and
understand all of our genes. But that hasn't stopped them from making dramatic
discoveries.
PMID- 11009719
TI - The double helix revisited. The man who launched the Human Genome Project
celebrates its success.
PMID- 11009720
TI - No doctor required. The FDA may expand the number of prescription drugs it
converts to over-the-counter use.
PMID- 11009721
TI - The new science of Alzheimer's. Racing against time--and one another--researchers
close in on the aging brain's most heartbreaking disorder.
PMID- 11009722
TI - Hot-flash relief. The list of alternatives to hormone-replacement therapy keeps
growing. What's a woman to do?
PMID- 11009723
TI - An Rx for pills--and politics. What's hot this election year? Drug costs and a
pair of thorny tax issues.
PMID- 11009724
TI - Little hope, less help. The epidemic has hit with devastating force--and things
will get much worse before they get better.
PMID- 11009725
TI - The politics of AIDS. When the President is a dissident.
PMID- 11009726
TI - The new antiseptics. Two novel approaches to an ancient scourge could someday
protect millions from runaway infections.
PMID- 11009727
TI - Grains of hope. Genetically engineered crops could revolutionize farming.
Protesters fear they could also destroy the ecosystem. You decide.
PMID- 11009728
TI - Ginseng surprise. An independent report finds that what's listed on a
supplement's label is not always what's inside.
PMID- 11009729
TI - Coordination of care: stage one in assessing rural managed care.
AB - This article provides a framework for assessing the role of managed care in
optimizing the mix of services to advance the health of rural populations.
Mindful of limited organizational and financial resources in many rural areas,
such assessments must carefully weigh the contribution of these resources to
effective management of care. The framework presented emphasizes the different
populations and different health conditions that a variety of care coordinators
may address more or less effectively. Attention to issues having to do with
organizational architecture and financial accountability of managed care should
flow from prior to consideration of care management.
PMID- 11009730
TI - Comparative performance assessment in managed care: data envelopment analysis for
health care managers.
AB - In health care markets increasingly dominated by managed care, health care
managers need sophisticated yet understandable comparative performance assessment
methods. Ideally, these methods should provide targets for the managers to
improve program or organization performance. This article reviews three
comparative performance methodologies with a comprehensive explanation of data
envelopment analysis (DEA). DEA is a form of linear programming that allows for
the inclusion of multiple input and output/outcome performance variables from a
virtually unlimited number of organizations, facilitating meaningful health
service provider comparative assessments.
PMID- 11009731
TI - Managed care liability and ERISA preemption.
AB - Patients enrolled in managed care organizations (MCOs) are concerned about
quality of care and restrictions imposed. There is concern about being harmed due
to the negligence of MCOs. Meanwhile, MCOs are protected by the federal
Employment Retirement Income Security Act (ERISA) of 1974, which preempts state
law claims and results in eliminating many of the recoveries otherwise available
to a harmed beneficiary in non-MCOs. This article reviews the ERISA exemption and
legal theories for patient redress.
PMID- 11009732
TI - "Low-tech" personal emergency response systems reduce costs and improve outcomes.
AB - A relatively inexpensive low-technology solution can be used by managed care
organizations (MCOs) to improve outcomes and significantly reduce health care
costs among community-residing elderly patients. Clinical studies indicate that
usage of monitored Personal Emergency Response Systems (PERS) reduce mortality
rates by nearly four times, reduce hospital utilization by 59 percent, and yield
a positive benefit-to-cost ratio of over seven to one (every dollar spent on PERS
results in $7.19 in health care cost savings).
PMID- 11009733
TI - Don't ask, don't tell: the incontinence conspiracy.
AB - Don't ask, don't tell is the attitude of both patients and doctors toward
symptoms of urinary incontinence (UI). This has serious fiscal implications for
managed care, because the consequences of not treating the condition increase the
annual cost of care by an estimated $3,941 per individual. Behavioral treatments
have clinical efficacy of 87 percent, and should be tried first, according to the
clinical practice guidelines published by the Agency for Health Care Policy and
Research. Attitudes about the condition, and historical and current
interventions, are discussed.
PMID- 11009734
TI - Information system powers innovative research project aimed at managing the care
of senior citizens.
AB - HealthAmerica Pennsylvania, Inc., in Pittsburgh, is aiming to increase access to
health care for senior citizens in its Advantra health plan in Pittsburgh. Under
its Senior Life Management program, Coventry Health Care, parent company of
HealthAmerica, hired nine personal service representatives (PSRs) and is asking
them to provide outreach to 5,000 senior citizens. The PSRs and other staff
members will get to know each senior citizen in the program, evaluate and
recognize their health needs, and develop methods to ensure that their needs are
met before any patient's condition becomes unnecessarily costly. The goal of this
innovative program is to improve access to health care for these 5,000 members
and thus improve their satisfaction with care and help to reduce health care
costs.
PMID- 11009735
TI - Interview with Bruce Vladeck, Institute for Medicare Practice.
PMID- 11009736
TI - Determinants of specialty physician practice management integration.
AB - Physicians increasingly organize strategically to mitigate the potentially
adverse impacts of managed care on practice incomes. There are alternative routes
to physician organizing. This article used a 1996-1997 survey of orthopedics and
obstetrics-gynecology (OB-GYN) practices in Memphis, Tennessee, to investigate
the determinants of specialty physician integration through physician practice
management (PPM) firms. The percentage of managed care contracts indicates a weak
but positive correlation with PPM integration. Different factors appear to
influence the likelihood of integration in different specialties.
PMID- 11009737
TI - The radical revolution of radiology.
AB - The radiologic segment of the health care industry has grown dramatically in size
and functions. The focus on cancer and heart disease has made it a key core
functional area for health systems and physician groups. Aggressive growth plans
are based on key strategies, high demand services, and other critical success
factors.
PMID- 11009739
TI - Understanding autism.
PMID- 11009738
TI - Right off the shelf. Non-prescription cholesterol drugs could open an era of do
it-yourself medicine.
PMID- 11009740
TI - Proposed PPS refinements would boost payments for sickest patients; add no new
Medicare money to system.
PMID- 11009741
TI - How to use the MDS quality indicators to improve patient care.
PMID- 11009742
TI - Industry reaction to the PPS refinement proposal is mixed.
PMID- 11009743
TI - The future of health status assessment.
PMID- 11009744
TI - Regulating the pharmaceutical industry: who really benefits?
PMID- 11009745
TI - Can peer-comparison feedback improve patient functional status?
AB - OBJECTIVE: To determine whether providing physicians with peer-comparison
feedback can improve patient functional status. STUDY DESIGN: Randomized,
controlled, comparative study. METHODS: Forty-eight primary care physicians at
Kaiser Permanente Woodland Hills, a group-model health maintenance organization
in southern California, were randomly assigned to an intervention group or a
control group. All physicians were informed that their elderly patients (randomly
selected patients aged 65 to 75) would be monitored. Physicians in the
intervention group received aggregated peer-comparison feedback data (physician
"report cards") on the functional status of their elderly patients. Physicians in
the control group received only general information that their patients'
functional status would be monitored. The effect of the intervention on patients'
functional status was determined by comparing responses to surveys completed by
the patients at baseline and after the intervention. RESULTS: Patients in both
the control and intervention groups had a statistically significant decrease in
functional status, including decreases in their ability to complete daily
activities and increases in pain. In addition, patients in the control group
reported a significant decrease in social activities, physical fitness, and
feelings. In the intervention group, patients also experienced a significant
decrease in social support. CONCLUSIONS: Educational interventions, including
peer-comparison feedback, did not result in improvements in patient functional
status. Research is desperately needed to identify interventions that can lead to
improved health for elderly patients.
PMID- 11009746
TI - Preventive service use and Medicaid managed care in New York City.
AB - OBJECTIVE: To examine the effect of managed care enrollment on the use of
preventive services among New York City's Medicaid population. STUDY DESIGN: An
analysis of survey results from a sample of Medicaid beneficiaries in managed
care plans and in traditional Medicaid. METHODS: This study is based on a 1994
survey of 1038 Medicaid beneficiaries enrolled in any of 5 managed care plans and
a comparison group of 410 beneficiaries in traditional Medicaid in New York City.
The survey data are used to examine the effect of managed care on the self
reported use of Pap smears, mammograms, and infant immunizations. We performed
bivariate analysis to compare the use of preventive services between managed care
enrollees and beneficiaries in traditional Medicaid. We also used multivariate
logistic analysis to explore this comparison, controlling for factors that may
confound the relationship. RESULTS: Medicaid beneficiaries in managed care were
no more or less likely to receive infant immunizations, Pap smears, or mammograms
than those in the traditional Medicaid program. CONCLUSIONS: Our analysis
suggests that Medicaid managed care and the traditional program performed the
same in getting appropriate preventive services to beneficiaries.
PMID- 11009747
TI - The impact of health insurance market reforms on market competition.
AB - OBJECTIVES: To assess the impact of state and federal health insurance market
reforms on the nature and extent of market competition. STUDY DESIGN:
Qualitative, comparative case studies in 7 states. METHODS: Two rounds of in
depth interviews were conducted with over 100 key informants from the insurance
industry. In each state, these sources included 2 to 4 regulators, 5 to 6
independent agents, and several sources at each of 4 to 5 of the top insurers.
Extensive documentary data relating to market activity were also collected. These
multiple sources of information and data were analyzed with both qualitative and
quantitative techniques. RESULTS: (1) Small-group health insurance markets are
highly competitive, both in price and in product innovation and diversity. (2) In
some of the more heavily regulated states, there is very little competition in
less-populated areas, especially for indemnity insurance. (3) The rapid growth of
managed care in the small-group market may have been precipitated by these
reforms. (4) Standardized benefit plans have not achieved their objectives. (5)
Competitive forces still focus to a considerable extent on risk selection
techniques. CONCLUSION: Small-group market reforms have not harmed market
competition and may have improved competition in several respects. However, these
reforms do not alter the fundamental orientation of competitive insurance
markets, which is to focus on risk selection factors and techniques to the extent
feasible.
PMID- 11009748
TI - An instrument to measure patient satisfaction with healthcare in an observational
database: results of a validation study using data from CaPSURE.
AB - OBJECTIVE: To validate a satisfaction measure for use in longitudinal,
prospective studies of patient care. STUDY DESIGN: Patients with biopsy-confirmed
prostate cancer (n = 228) who were enrolled in CaPSURE (Cancer of the Prostate
Strategic Urologic Research Endeavor) completed a self-administered questionnaire
that included a health-related quality-of-life and satisfaction measure. A subset
of patients completed the questionnaire again within 30 days. METHODS: The
satisfaction measure contained 6 individual subscales: overall satisfaction with
care, contact with providers, confidence in providers, communication skills,
humaneness, and a summary scale. Six items surveyed patients' willingness to
participate in decision making (participatory style), and these were averaged
into a single score. Variability, reliability, stability, and validity were
evaluated. RESULTS: Responses to the items varied substantially. The overall
satisfaction scale demonstrated good internal consistency reliability (Cronbach
alpha = 0.82) and moderate test-retest reliability (0.62), and it could
discriminate between groups of individuals expected to differ with regard to
satisfaction (by age and disease stage). Subscale internal consistency
reliability (0.37-0.54) and stability (0.38-0.63) were weaker, suggesting that
only a single scale should be reported. The participatory scale performed poorly
and could not be recommended for future use. CONCLUSION: The overall satisfaction
measure developed for this study demonstrated good reliability and validity and
should be useful in other population-based studies in conjunction with other
outcome measures.
PMID- 11009749
TI - Acne vulgaris: pathogenesis and therapeutic approach.
AB - AUDIENCE: This activity is designed for primary care providers, internists, and
general audiences. GOAL: To provide the reader with a basic understanding of the
pathogenesis of acne vulgaris and the rationale behind several treatment options.
Clinicians should be aware of treatment strategies for various subtypes of acne
vulgaris. OBJECTIVES: 1. To describe the emotional and financial impact of acne.
2. To describe the differential diagnosis of acne vulgaris. 3. To discuss acne's
pathogenesis. 4. To provide information on topical therapy for the treatment of
acne vulgaris. 5. To discuss oral therapy for the treatment of acne vulgaris.
PMID- 11009750
TI - Parkinson's disease: focus on management alternatives.
AB - AUDIENCE: This activity is designed for physicians, pharmacists, nurses, health
planners, directors of managed care organizations, and payers of health services.
GOAL: To understand the impact that Parkinson's disease has on patients and to
identify areas of drug therapy that can be optimized to improve a patient's
quality of life. OBJECTIVES: 1. Discuss the epidemiology and pathophysiology of
idiopathic Parkinson's disease (IPD). 2. Identify causes of secondary
parkinsonism and medications associated with drug-induced parkinsonism. 3.
Discuss the cardinal and secondary manifestations of IPD. 4. Outline the 6 stages
of IPD. 5. Identify therapeutic alternatives for various levodopa treatment
failures. 6. Identify the 3 newer antiparkinson agents and state their mechanisms
of action, common adverse effects, drug interactions, and appropriate use. 7.
Identify the appropriate use, common adverse effects, and drug interactions of
dopamine agonists, anticholinergic agents, monoamine oxidase inhibitors, and
catechol-O-methyltransferase inhibitors in Parkinson's disease therapy.
PMID- 11009751
TI - Optimizing quality of care and cost effectiveness in treating allergic rhinitis
in a managed care setting.
AB - Allergic rhinitis is a common condition in managed care populations. The direct
medical cost of rhinitis exceeded $3 billion in 1996, and an additional cost of
$4 billion resulted from the exacerbation of other concomitant conditions, such
as asthma or otitis media. Costs continued to increase in 1999; sales of
prescription antihistamines and nasal steroids exceeded $3 billion and $1
billion, respectively. The indirect costs of allergic rhinitis include lost work
productivity, reduced performance and learning, and increased workplace and
traffic accidents. Rhinitis treatments include allergen avoidance, over-the
counter (OTC) sedating antihistamines, nonsedating antihistamines, nasal
steroids, and immunotherapy. Allergen avoidance strategies for patients with
asthma and rhinitis are ineffective or are of very limited benefit. Allergists
criticize the use of OTC sedating antihistamines, which are associated with
reduced learning and performance even when sedation does not occur. Evidence
based literature reviews of clinical trials have shown that nasal steroids are
more effective than nonsedating antihistamines in the treatment of rhinitis. The
most commonly prescribed nasal steroid, fluticasone, has been shown to be
effective in treating rhinitis and in improving patients' quality of life. It is
also more cost effective than the most commonly prescribed antihistamine,
loratadine. Clinical trials have indicated that immunotherapy is expensive and of
limited benefit. As these evidence-based findings are used to develop managed
care treatment guidelines, nasal steroids are likely to be recommended as the
first-line treatment for rhinitis, which should result in lower treatment costs
and improved outcomes for patients with rhinitis.
PMID- 11009752
TI - Computerization saves money, time, and trees.
PMID- 11009753
TI - Center will establish rehab care benchmarks.
PMID- 11009754
TI - Why don't doctors follow guidelines?
PMID- 11009755
TI - Medication errors top patients' worry list.
PMID- 11009756
TI - Tracking your medical errors just became a priority.
PMID- 11009757
TI - Two hospitals solve adverse events problems.
PMID- 11009758
TI - Don't accept ED's claim it's too busy to benchmark.
PMID- 11009759
TI - Teamwork helps cut ED wait times.
PMID- 11009760
TI - Benchmarking focuses on perfecting pastoral care.
PMID- 11009761
TI - Getting a pastoral care program off the ground.
PMID- 11009762
TI - Regional benchmarks show how you stack up.
PMID- 11009763
TI - Benchmarking crucial for small, rural facilities with few resources.
PMID- 11009764
TI - Monitoring system saves hospital $180,000 a year.
PMID- 11009765
TI - Communication eases consolidation conflicts.
PMID- 11009766
TI - Climbing hospital stays level off in western U.S.
PMID- 11009767
TI - Who will lose under the outpatient PPS?
PMID- 11009768
TI - Perspectives. Regression to the mean: PPOs, risk-sharing are market mainstays.
PMID- 11009769
TI - Perspectives. Congressional outlook 2000: you snooze, you lose.
PMID- 11009770
TI - Perspectives. Surplus makes both 'restraint,' new programs possible in budget
proposal.
PMID- 11009771
TI - Marketplace. Provider risk-sharing in managed care: still viable despite current
unpopularity.
PMID- 11009772
TI - Perspectives. The uninsured: local efforts in state, federal, global contexts.
PMID- 11009773
TI - Define improvement opportunities to cut 'data denial'.
PMID- 11009774
TI - Studies offer benchmarks for costs, rates of prostate surgery.
PMID- 11009775
TI - Competing hospitals use regional database to cut cardiac surgery mortality.
PMID- 11009776
TI - Canada: using our most valuable natural resource to transform health care.
AB - Canada is recognized around the world as a wonderful outdoor experience with its
wealth of natural resources and vibrancy. As Canada has evolved through the
years, this vibrancy has continued to resonate through its communities and
people. Historically, Canadians are well known for their pioneering and frontier
spirit, which is a precious commodity. Now, that spirit, wisdom, talent, and
potential of Canadians are being tapped to begin to change its health care
system.
PMID- 11009777
TI - Henk Tjassing: on the road to Suriname. Interview by Margaret J. Cushman.
PMID- 11009778
TI - Cultural competence in patient education.
AB - As a community health nurse, have you tested your cultural consideration quotient
in patient education recently? Can you define the difference between
ethnocentrism and multiculturalism? Do you find that you and your colleagues work
with more or less transcultural nursing in your daily practice? Find out why
cultural competence is vital to nurses' success in the 21st century.
PMID- 11009779
TI - A salute to congressman Robert A. Weygand. Advocate for the elderly. Interview by
Val J. Halamandaris.
PMID- 11009780
TI - The Frances Payne Bolton WHO Collaborating Center: promoting home care globally.
AB - Since its designation as a World Health Organization Collaborating Center in
1993, the Frances Payne Bolton School of Nursing has been committed to furthering
the development of home care practices throughout the world. Through research,
education, conferences, and publications, the Bolton School is promoting the
efforts made by home care nurses throughout the world.
PMID- 11009782
TI - Hospice forum. Resources for public engagement activities; advances in clinical
policy for end-of-life care.
PMID- 11009781
TI - Elder suicide: a preventable tragedy.
AB - Reported suicides claim more than 32,000 lives annually in the United States.
More than 6,200 of these deaths occur among those 65 years of age or older.
Suicide is the third leading cause of death among the elderly. These deaths are
unnecessary and most are avoidable. Elder suicides happen because not enough is
done to prevent them. Home care agencies can do something about this situation.
PMID- 11009783
TI - Reaching out ... through communication.
PMID- 11009784
TI - PPS: blessing or curse?
PMID- 11009785
TI - A conversation with Sandra R. Hernandez, MD. Interview by Val J. Halamandaris.
PMID- 11009786
TI - Preventing nursing turnover in home care.
AB - Turnover is costly to any organization. Frequently, turnover creates a ripple
effect that is felt by the agency, its patients, and staff at all levels. The
very nature of home care creates an environment in which nurses are not visible
in the office every day. It is difficult to track the activities of new employees
on a day-to-day basis to know how they are progressing through the orientation
process. What causes turnover among registered nurses within the first six months
of employment? One agency shares its story and related findings.
PMID- 11009787
TI - Changing times in rehab staffing.
AB - Historically, a low supply of physical and occupational therapists existed in the
home care marketplace. Home care agencies have had to contract with private
practices and accept therapists who could only provide two or three visits a week
to keep up with the demand. However, cutbacks have occurred at the acute, sub
acute, and rehabilitation levels of inpatient care. Now, many therapists who
would not have considered home care employment in the past are asking for
interviews. For once, many home care agencies have the opportunity to carefully
select the therapists they hire.
PMID- 11009788
TI - A tribute to Beverly Malone. Interview by Val J. Halamandaris.
PMID- 11009789
TI - The greying of the profession.
AB - As the 21st century begins, Americans can expect to see changes across the health
care spectrum. With the drive toward market parity in the management of health
care resources, it is easy to lose sight of some critical elements of the health
care system that may affect the quality and delivery of care. Specifically, the
work force that cares for patients in the hospital, the home, or other care
settings will shift. The nursing profession will not be immune to this shift and,
as nurses reach retirement age and leave the profession, their departure may
leave a void that could take years to fill and profoundly alter the quality of
care available.
PMID- 11009790
TI - Pre-employment intentions of home care aides.
AB - The demand for home care aides (HCA) is projected to increase substantially over
the next several years. One of the reasons for this projection is the high
turnover rates associated with the occupation. Although there are many reasons
for the high turnover after HCAs have been hired, their pre-employment intentions
are unclear. A better understanding of HCAs' pre-employment intentions may help
to decrease recruitment and training costs for home care agencies and improve
continuity of care for clients.
PMID- 11009791
TI - Determining the scope of practice for home care aides.
AB - Because of recent fiscal challenges, home health agencies are forced to seek the
most cost-effective methods of providing care. Many agencies are attempting to
redefine the scope of practice for home care aides, hoping to determine how to
best use these individuals in providing high-quality, cost-effective care. A
study was conducted to determine what tasks should be included in the aide's
scope of practice. The high response rate to this study seems to indicate a great
deal of interest and the need to resolve this issue.
PMID- 11009792
TI - Nine tips to improve your recruitment advertising.
PMID- 11009793
TI - Humor at work: could this keep staff happy?
PMID- 11009795
TI - Wanted ... angels on earth.
PMID- 11009794
TI - Fatigue: the most important consideration for the patient with cancer.
AB - The Fatigue Coalition--a multidisciplinary group of medical practitioners,
researchers, and patient advocates--conducted a study to determine the effects of
fatigue on cancer patients. The study, published in September 1998, examined
cancer patients, caregivers, and oncologists. This survey presents new
information about how fatigue is perceived by the patient, caregiver, and
oncologist. In response to the survey, the group developed a series of
educational and research initiatives designed to help patients and physicians
better understand chemotherapy-related fatigue and provide successful
interventions.
PMID- 11009796
TI - Integrating effective home care aide recruitment & retention strategies.
PMID- 11009797
TI - NAHC's legislative agenda tackles mission-critical issues.
PMID- 11009798
TI - The new hospice compliance plan: defining and addressing risk areas.
AB - The Department of Health and Human Services' (HHS) Office of the Inspector
General (OIG), has advised hospices and other health care providers to formulate
effective controls to ensure compliance with federal and state statutes, rules,
and regulations, and private-payor health care program requirements. The recently
released guidelines provide a blueprint for developing such programs. This is the
first of four installments that focus specifically on the 28 risk areas
identified in the guidance and offer strategies for incorporating them in a
hospice compliance program. The authors have organized the 28 risk areas under 9
topic domains to simplify the task of tackling the guidance. This article covers
the first two areas: Admission/Certification/Recertification and Billing.
PMID- 11009799
TI - Ensuring accuracy of OASIS data as home care moves toward PPS.
PMID- 11009800
TI - Skilled nurses in schools: IDEA (Individuals with Disabilities Education Act) at
work.
AB - Home care agencies have an opportunity to create a new revenue stream while
helping disabled children receive their education within schools, instead of at
home, through the Individuals with Disabilities Education Act. This article
examines the law itself, related court cases, problems with implementation, and
implications for home care providers. Home care agencies must demonstrate to
schools that they can deliver the services the schools need to supplement their
nursing staffs under IDEA.
PMID- 11009801
TI - Reflections on home care. Where we've been, where we're going, why we must get
there.
PMID- 11009802
TI - Taking a stand. Members of Congress praise home care's benefits importance.
PMID- 11009803
TI - The lowdown on colon cancer.
PMID- 11009804
TI - Health care delivery at the millennium: 10-year forecast.
PMID- 11009805
TI - System losses, poor capitation profitability, bankruptcy warnings signal distress
for docs.
PMID- 11009807
TI - Don't expect instant savings when implementing Medicaid managed care.
PMID- 11009806
TI - Planning for clinical services within a regional health system.
PMID- 11009808
TI - New data project median hospital's margin will be -0.41 in 2002 because of BBA's
impact.
PMID- 11009809
TI - Avoid politics by establishing objective criteria for capital budget decision
making.
PMID- 11009810
TI - Hospitals face major changes in 2000.
PMID- 11009811
TI - Developer offers 'win-win' construction solution for capital-starved hospitals.
PMID- 11009812
TI - HIPAA offers hospitals the good, the bad and the ugly.
PMID- 11009813
TI - After more major acquisitions, affiliations, Healtheon says big pieces now in
place.
PMID- 11009814
TI - Can we afford a customer service initiative?
PMID- 11009815
TI - Strong service, strong brand help systems establish respected, recognized name.
PMID- 11009816
TI - Hospitals are beginning to make creative use of excess capacity.
PMID- 11009817
TI - Better HMO rates bring good news, bad news.
PMID- 11009819
TI - Learning from our customers.
PMID- 11009818
TI - CEO of big California capitated physicians group isn't complaining about managed
care.
PMID- 11009820
TI - Beyond managed care.
PMID- 11009821
TI - The tug-of-war over Medicare funding.
PMID- 11009822
TI - "Best-in-class": an interview with John T. Bigalke.
AB - John T. Bigalke, FHFMA, MBA, CPA, is national director, healthcare assurance &
advisory services, Deloitte & Touche LLP. Bigalke began his career in health care
in 1977 as a staff auditor and consultant with a Big Five accounting firm. In
1983, he moved to another Big Five firm, where he spent 15 years in leadership
positions, including vice chairman of the healthcare practice, before moving to
Deloitte & Touche in 1998. A member of HFMA since 1980, he served on HFMA's
National Board of Directors from 1997 to 2000.
PMID- 11009823
TI - Integration strategies in transition: an interview with Russell C. Coile, Jr.
AB - Russell C. Coile, Jr., is a nationally recognized futurist and speaker
specializing in healthcare business strategy and market forecasting, and vice
president and national strategy consultant for Southfield, Michigan-based
Superior Consultant Company, Inc. Coile also has written seven books dealing with
the future of health care, including New Century Healthcare: Strategies for
Providers, Purchasers, and Plans, which was published this year. Coile spoke with
HFM to share his views regarding the future of IDSs and how these organizations
may need to modify their strategies to ensure their long-term financial success.
PMID- 11009824
TI - Clinicians hold the key to profitable managed care contracting.
AB - A managed care contract's effect on the financial health of an organization is
related in part to utilization and quality management issues. Physicians and
other clinicians who are involved in case management can illuminate how these
issues, in relation to the contract terms, can affect the organization's bottom
line. Clinicians should be part of a contract-negotiating team that also includes
financial professionals and contract negotiators, in addition to legal counsel.
PMID- 11009825
TI - Full amnesty could encourage provider self-disclosure.
AB - The Federal government's current policy toward healthcare providers that
voluntarily disclose improprieties has been ineffective because it offers no
guarantee of immunity from prosecution. To be successful, a self-disclosure
program must offer real incentives to providers to come forward. The government's
self-disclosure programs with respect to tax, environmental, and antitrust laws
provide models for an effective amnesty program. The success of these three
programs, and particularly of the antitrust program, suggests that healthcare
providers would be encouraged to come forward and disclose improprieties if,
under certain specific conditions, the OIG and DOJ offered a guarantee of full
amnesty to the entity and its officers, directors, and employees.
PMID- 11009826
TI - Cost-effective compliance for the small provider.
AB - Small provider organizations often have limited resources with which to implement
a compliance program. The Office of Inspector General (OIG) has indicated that a
small organization may take a less formal approach to compliance and develop a
compliance program that fits its budget and resources. But small providers should
take seriously the need for a compliance program despite the OIG's greater
latitude toward small organizations. Whatever the size of their budget, small
providers should emphasize due diligence and good-faith approaches to compliance
to demonstrate to investigators and employees that they have made compliance a
priority. These efforts can encourage the OIG to look more favorably upon the
organization in the event of a compliance breach and also can improve the
organization's financial performance by improving overall management of the
organization.
PMID- 11009827
TI - APCs challenge hospital EDs and outpatient clinics.
AB - As the uneasily awaited Medicare outpatient prospective payment system becomes
reality July 1, hospital emergency department and outpatient clinics face an even
greater need for accurate coding models and systems, as well as vigorous cost
reduction strategies. By the nature of the services they provide, such facilities
will find securing adequate payment for appropriate, quality care to be a complex
and challenging task. Those organizations that have prepared effectively,
however, may benefit under the prospective payment system.
PMID- 11009828
TI - Quality vs. costs? A survey of healthcare purchasing habits and concerns.
AB - The results of the Fifth Annual Survey Report on Purchasing Value in Health Care
show that to help control rising healthcare costs, most employers are offering
employees more choice when it makes sense but fewer plans when they can strike a
better bargain. Providers' favored tactics to reduce costs include reducing
waste, reducing or eliminating certain services, increasing fees for some
services, and improving medical management and information systems capabilities.
Health plans overwhelmingly are focusing on increasing premiums to employers;
they also are attempting to improve medical management and information systems
capabilities. Many employers, health plans, and providers want to make their
current arrangements work better. Improving the quality of customer service to
purchasers and their employees is a top priority with both health plans and
providers.
PMID- 11009829
TI - PRRB issues new appeals hearing instructions.
PMID- 11009830
TI - Automated compliance checker helps ensure billing accuracy.
PMID- 11009831
TI - Meeting the challenges of the outpatient PPS.
PMID- 11009832
TI - Investors can benefit from charitable giving.
PMID- 11009833
TI - Assessment of biotechnology drugs: what are the issues?
PMID- 11009834
TI - Pa. sues former AHERF execs.
PMID- 11009835
TI - Mass. fights Harvard University for name.
PMID- 11009836
TI - Whistleblowers make less off Medicaid.
PMID- 11009837
TI - Tenn. systems forgo joint custody.
PMID- 11009838
TI - Columbia streamlining becomes clearer.
PMID- 11009839
TI - A two-front battle. Hospitals fight error reporting as they seek higher payments.
PMID- 11009840
TI - Pa. weighs rules on not-for-profit deals.
PMID- 11009841
TI - Forcing the issue. Californians set to use their electoral clout to place
healthcare on the presidential front burner.
PMID- 11009842
TI - Voting for a single-payer plan. Washington state coalition working to put
universal-coverage initiative on the November ballot.
PMID- 11009843
TI - On a quality roll. Michigan hospital wins NCQHC's top award for being 'ahead of
the pack in many ways'.
PMID- 11009844
TI - AHA moves on medical errors. As one hospital calls IOM report 'bang-on right,'
association begins a data quest.
PMID- 11009845
TI - Waving goodbye to healthcare. Execs are being driven away; it may be time to take
a break before the industry breaks you.
PMID- 11009846
TI - Organized doctors. Unionization of physicians a small but significant force as
relationships with hospitals change.
AB - The number of unionized physicians is still small, but those doctors are becoming
a force to be reckoned with as organizing continues to grow and the fledgling
union formed by the American Medical Association becomes more established. "The
state of the unions in healthcare is excellent," says Barry Liebowitz, M.D.,
(left) president of the Doctors Council, which represents 16,000 physicians
nationally.
PMID- 11009847
TI - Five-hospital system comes undone.
PMID- 11009848
TI - Indianapolis casts wider net in healthcare sprawl. System consolidation fuels
growth; costs remain high.
PMID- 11009849
TI - Wanted: more data from not-for-profits. Investors seek more-frequent reports on
finances; organizations divided over best practices.
PMID- 11009851
TI - Medicare reform plans take blows.
PMID- 11009850
TI - CHA taking a close look at itself. Task force formed to address internal tensions
resulting from association's revamp.
PMID- 11009852
TI - Building health promotion into the national agenda: Washington, DC, February 14
16, 2001; a call to action.
PMID- 11009853
TI - Effects of leadership style and group dynamics on enjoyment of physical activity.
AB - PURPOSE: The primary purpose of this study was to examine the independent and
combined effects of leadership style and group dynamics on the enjoyment of
physical activity. DESIGN: A completely randomized 2 x 2 factorial design was
used in which the manipulation of "leadership style" (socially enriched vs.
bland) was crossed with a manipulation of "group dynamics" (socially enriched vs.
bland). SETTING: The study was conducted in an aerobics studio on a university
campus. SUBJECTS: The sample included 48 male and 42 female undergraduate
students who were moderately active. INTERVENTION: Each participant was involved
in a single session of step aerobics. A female graduate student provided either
an enriched or bland series of interactions to manipulate leadership style, and a
trained group of planted undergraduates was used to promote either an enriched or
bland group environment. MEASURES: The outcome measures of interest were
enjoyment and the probability of engaging in a similar activity in the future.
RESULTS: Participants in the enriched leadership style plus enriched group
dynamics condition reported higher enjoyment than did participants in the other
three conditions. On average, the level of enjoyment was 22.07% higher in this
condition than in the other three conditions (p < .001). The probability of
future involvement was 13.93% higher for participants in the enriched group
environment, irrespective of leadership style (p < .03). CONCLUSIONS: Enjoyment
during physical activity is optimized when a positive and supportive leadership
style is coupled with an enriched and supportive group environment. Future
research is required to extend these findings to other activities and
populations.
PMID- 11009854
TI - The impact of the transcendental meditation program on government payments to
physicians in Quebec: an update.
AB - PURPOSE: To determine whether practice of the Transcendental Meditation (TM)
technique can affect medical expenses. DESIGN: The evaluation was a quasi
experimental, longitudinal, cost-minimization study. SETTING: Province of Quebec,
Canada. SUBJECTS: This study involved 1418 Quebec health insurance enrollees who
practiced the TM technique compared with 1418 subjects who were randomly selected
from enrollees of the same age, sex, and region. TM subjects had chosen to begin
the technique prior to learning about and choosing to enter the study. MEASURES:
This 14-year, pre- and postintervention study retrospectively assessed government
payments to physicians for treating the TM and comparison groups. Other medical
expense data for individuals were unavailable. Data were inflation-adjusted. For
each subject, least squares regression slopes were calculated to estimate pre-
and postintervention annual rates of change in payments. We compared the groups'
means and 1%, 5%, and 10% trimmed means (robust estimators) of the slopes.
RESULTS: Before starting meditation, the yearly rate of increase in payments
between groups was not significantly different (p > .17). After commencing
meditation, the TM group's mean payments declined 1% to 2% annually. The
comparison group's payments increased up to 11.73% annually over 6 years. There
was a 13.78% mean annual difference (p = .0017). CONCLUSIONS: The results suggest
that the TM technique reduced payments to physicians between 5% and 13% annually
relative to comparison subjects over 6 years. Randomized studies are recommended.
PMID- 11009856
TI - Low awareness of cardiovascular disease risk among low-income African-American
women.
AB - Focus groups were conducted with low-income African-American women in six
different community settings in Northern California to assess their awareness of
and concern for cardiovascular disease (CVD). These women had low awareness of
the prevalence of CVD, attributed CVD to stress and low socioeconomic status, saw
the media as an important source of health-related knowledge, and saw a need for
more community awareness on CVD among African-American people.
PMID- 11009855
TI - Hispanic women's breast and cervical cancer knowledge, attitudes, and screening
behaviors.
AB - PURPOSE: This study examined breast and cervical cancer knowledge, attitudes, and
screening behaviors among different Hispanic populations in the United States.
DESIGN: Data were collected from a random digit dial telephone survey of 8903
Hispanic adults from eight U.S. sites. Across sites, the average response rate
was 83%. SETTING: Data were collected as part of the baseline assessment in a
national Hispanic cancer control and prevention intervention study. SUBJECTS:
Analysis was restricted to 2239 Hispanic women age 40 and older who were self
identified as either Central American (n = 174), Cuban (n = 279), Mexican
American (n = 1550), or Puerto Rican (n = 236). MEASURES: A bilingual survey
instrument was used to solicit information on age, education, income, health
insurance coverage, language use, U.S.-born status, knowledge of screening
guidelines, attitudes toward cancer, and screening participation. Differences in
knowledge and attitudes across Hispanic groups were assessed by either chi-square
tests or analysis of variance. Logistic regression models assessed the influence
of knowledge and attitudes on screening participation. RESULTS: The level of
knowledge of guidelines ranged from 58.3% (Mexican Americans) to 71.8% (Cubans)
for mammography, and from 41.1% (Puerto Ricans) to 55.6% (Cubans) for Pap smear
among the different Hispanic populations. Attitudes also varied, with Mexican
Americans and Puerto Ricans having more negative or fatalistic views of cancer
than Cuban or Central Americans. Knowledge was significantly related to age,
education, income, language preference, and recent screening history. Overall,
attitudes were not predictive of mammography and Pap smear behavior. CONCLUSIONS:
Factors related to mammography and Pap smear screening vary among the different
Hispanic populations. Limitations include the cross-sectional nature of the
study, self-reported measures of screening, and the limited assessment of
attitudes. The data and diversity of Hispanic groups reinforce the position that
ethno-regional characteristics should be clarified and addressed in cancer
screening promotion efforts. The practical relationships among knowledge,
attitudes, and cancer screening are not altogether clear and require further
research.
PMID- 11009857
TI - Tailoring and targeting a worksite health promotion program to address multiple
health behaviors among blue-collar women.
AB - PURPOSE: This study examined the relationship between health risks, health
behaviors, stages-of-change, and behavior change priorities among blue-collar
women participating in a worksite health promotion study. DESIGN: Cross
sectional. SETTING: Rural manufacturing worksites in North Carolina. SUBJECTS:
Participants were 859 women aged 18 and over. MEASURES: The self-administered
questionnaire assessed smoking, exercise, nutrition (fat, fruits, and
vegetables), and breast and cervical cancer screening behaviors. In addition,
demographics, body weight, perceived health, stages-of-change, and priority for
behavior change were measured. Chi-square tests and regression analysis were used
to assess statistical significance. RESULTS: Overall, 28% of women smoked, 37%
were completely sedentary, 82% consumed less than five daily servings of fruits
and vegetables, and the majority were overweight. The dominant stage of change
for each of the lifestyle behaviors was contemplation, whereas most women were in
the action stage for cancer screening. When asked to prioritize the behavior they
most wanted to change, the majority of women chose healthy eating and/or
exercise. CONCLUSIONS: The findings suggest that blue-collar women in this study
had multiple health risks and were interested in changing multiple health
behaviors. Allowing women to choose the behavior(s) on which they are ready to
focus may be a promising approach to tailoring interventions for this population.
PMID- 11009858
TI - Closing of the Seniors Plus Social HMO in Minneapolis operated by HealthPartners
(formerly Group Health, Incorporated)
PMID- 11009859
TI - The application of unisex annuity tables to retirement plans.
AB - Protections in pension law meant to increase women's pension income must be
reevaluated in light of the increased use of defined contribution plans. One such
protection is discussed: the requirement that pension plans use unisex annuity
tables in calculating monthly benefits for retirees. Its usefulness is examined
when applied to defined contribution plans. Legal reforms necessary to insure the
use of unisex annuity tables are examined.
PMID- 11009860
TI - A global perspective on social security programs for the aged.
AB - The social security programs that have become widely established in countries
around the globe vary greatly in their design features. The difference among the
programs invites questions regarding the relative strength of their designs. One
hundred and sixty-four programs are assessed on three design dimensions: benefit
eligibility, qualifying eligibility criteria, and benefit provision. The analysis
shows that the best-designed old-age programs can be found in Western Europe and
Australasia.
PMID- 11009861
TI - Coordinating health, extended care, and community support services: reforming
aged care in Australia.
AB - Under pressure to maximize the cost-effectiveness of programs, efforts to improve
coordination have become increasingly central to the development of the broader
health and welfare service delivery system in Australia in the past few years.
This article reviews recent experience in two related fields: (1) the
coordination of different community care services for older people and people
with disabilities, funded by the Home and Community Care program; and (2) the
attempt to enhance links between community and residential care services,
hospitals, and other health care providers. Why coordination has emerged as such
an important issue in the field of community care and, increasingly, across the
entire system of what the Australian government now terms health and family
services is discussed. A number of measures that have been introduced or are
proposed to improve a coordination of services are briefly reviewed. These range
from individualistic approaches based on information and referral, through
schemes involving gatekeeping, case management and brokerage of services, to
models involving the reconfiguration of organizational structures, linkages, and
finances. These measures are not mutually exclusive and are increasingly likely
to be applied in more complex mixed models of service coordination. It is argued
that coordination at the level of direct-service provision is difficult if
government policies that direct services lack coordination.
PMID- 11009862
TI - Physicians and clergy as facilitators of formal services for older adults.
AB - Researchers have sought to understand the determinants of the use of in-home and
community-based services in order to better serve the needs of older adults. One
component frequently included in formal service utilization models is the role of
individuals who exert an influence on the service use process. An analysis of in
depth interviews conducted with 115 older adults revealed the important
facilitating role that physicians and religious leaders play in encouraging the
use of these services. The sample, which included African-American and white
adults age 65+ from rural and urban environments, described various ways in which
these "facilitators" influence the use of formal services. These ways include:
(1) supplying instrumental support either by "ordering" a particular program for
or linking the elder with the program and (2) providing informational and
affective support, including advising or recommending the use of a program,
conveying necessary background on formal services, and legitimizing the use of
formal services. Regardless of personal characteristics (such as ethnicity and
residence), a majority of elders in the sample recognized the important role
played by physicians, and clergy. The acknowledgement of the role played by these
facilitators should be viewed as an opportunity for physicians and clergy to
enhance the knowledge and appropriate use of needed formal services for elders.
In addition, these findings have policy implications for the current provision of
aging services.
PMID- 11009863
TI - Effects of incentive size and timing on response rates to a follow-up wave of a
longitudinal mailed survey.
AB - Young adults who had previously participated in a longitudinal survey of youth
were sent a questionnaire. They were randomly assigned to receive a $20
prepayment, a $20 postpayment, or a $25 postpayment for participation in the
latest survey. Those in the large incentive condition were 7 percentage points
more likely to return a survey than those in the smaller, postpayment group.
Prepayment had a smaller, less reliable effect. Effects of incentive magnitude
and timing were consistent at each month of the study period; only better high
school grades distinguished early responders from late responders. Nonresponders
had characteristics suggestive of low social conformity and were more likely than
responders to be African American and male and have low SES. The discussion
centers on motivations for participating in research and differences in the
incentives likely to promote continued response versus initial study enrollment.
PMID- 11009864
TI - Program variation in treatment outcomes among women in residential drug
treatment.
AB - Multilevel modeling was used to assess the program characteristics associated
with treatment retention among 637 women in 16 residential drug treatment
programs in the Drug Abuse Treatment Outcome Study. Women who were pregnant or
had dependent children had higher rates of retention in programs in which there
were higher percentages of other such women. Longer retention was associated with
higher rates of posttreatment abstinence. Bivariate analyses showed that programs
with higher proportions of pregnant and parenting women provided more services
related to women's needs. The findings support the provision of specialized
services and programs for women in order to improve outcomes of drug abuse
treatment.
PMID- 11009865
TI - You got a problem with that? Exploring evaluators' disagreements about ethics.
AB - A random sample of American Evaluation Association (AEA) members were surveyed
for their reactions to three case scenarios--informed consent, impartial
reporting, and stakeholder involvement--in which an evaluator acts in a way that
could be deemed ethically problematic. Significant disagreement among respondents
was found for each of the scenarios, in terms of respondents' views of whether
the evaluator had behaved unethically. Respondents' explanations of their
judgments support the notion that general guidelines for professional behavior
(such as AEA's Guiding Principles for Evaluators) can encompass sharply
conflicting interpretations of how evaluators should behave in specific
situations. Respondents employed in private business/consulting were less likely
than those in other settings to believe that the scenarios portrayed unethical
behavior by the evaluator, a finding that underscores the importance of taking
contextual variables into account when analyzing evaluators' ethical perceptions.
The need for increased dialogue among evaluators who represent varied
perspectives on ethical issues is addressed.
PMID- 11009867
TI - Technology breeds insecurity: privacy becomes a federal policy.
PMID- 11009866
TI - Theory-based evaluation in practice. What do we learn?
AB - Theory-based evaluation (TBE) explores the how and why of program success or
failure. Advocates of TBE claim that it produces information unavailable in
traditional process and outcome studies. This article examines six published
papers of TBEs. It finds that the authors of the papers do not always make
explicit the relation of their data to the theory of the program. Nevertheless,
it was evident in one or more cases that TBE identified unnecessary program
components, located intermediary changes, raised new questions, contributed to a
paradigm shift, highlighted the difficulties of taking successful pilot programs
to scale, and provided clarity and focus for the evaluation. Interestingly, in
none of the studies was the original theory completely right. Lessons for the
future of TBE are drawn.
PMID- 11009869
TI - Learning the laws behind compliance.
PMID- 11009868
TI - Conducting your own internal assessment. American Health Information Management
Association.
PMID- 11009870
TI - Exploring IT opportunities for HIM professionals.
PMID- 11009871
TI - Healthcare trends--the big picture. Megatrends you need to know about.
PMID- 11009872
TI - Healthcare trends. The industry response to healthcare change. New models for
hospitals, health systems.
PMID- 11009873
TI - Healthcare trends. The industry response to healthcare change. Long-term care:
keeping the promise, today and tomorrow.
PMID- 11009874
TI - Healthcare trends. The industry response to healthcare change. Home care poised
for greater demand.
PMID- 11009875
TI - Healthcare trends. Changing with the times. Panel discussion.
PMID- 11009876
TI - Confronting ethical dilemmas on the job: an HIM professional's guide.
PMID- 11009877
TI - Keeping an eye on the Joint Commission's new core measures.
PMID- 11009878
TI - Practice brief. Disaster planning for health information (updated). American
Health Information Management Association.
PMID- 11009879
TI - The cornerstones of outstanding leadership.
PMID- 11009880
TI - Reviewing diagnostic coding for mental disorders.
PMID- 11009881
TI - Mental disorders pose coding challenge.
PMID- 11009882
TI - Speaking up for HIM.
PMID- 11009883
TI - Face lift in a jar?
PMID- 11009884
TI - Different strokes. The misdiagnosis of a former President's illness shows the
importance of recognizing symptoms.
PMID- 11009885
TI - Technology part 1: the Internet--opportunities & threats.
AB - This is the first article in a three-part series about technology and its impact
on healthcare systems and the business of health care. This article explores the
use and implications of Internet and Web-based technologies for physicians,
managed care organizations healthcare providers. The second article will present
clinical and pharmaceutical technologies. The third article will profile systems
that are successfully exploiting all of these technologies.
PMID- 11009886
TI - Profile: Baptist Health System, Birmingham.
PMID- 11009887
TI - Health plans: not always safe. A cycle of HMO failures leave some consumers
scrambling for coverage--and some without it.
PMID- 11009888
TI - Calcium overload. After years of neglect, this vital mineral is showing up in
everything from OJ to muffin mix. Are we getting too much of a good thing?
PMID- 11009889
TI - Tapping the power of the placebo. Sugar pills are potent medicine when taken in
the right spirit. Can we put them to practical use?
PMID- 11009890
TI - Unemployment ramifications. A study of Deckerville Community Hospital.
PMID- 11009891
TI - The evolving role of physician assistants.
PMID- 11009892
TI - A house of peace.
PMID- 11009893
TI - Coaching for renewal and growth.
PMID- 11009894
TI - After the layoffs.
PMID- 11009895
TI - Current issues in Medicaid managed care.
PMID- 11009896
TI - It's all in the mix.
PMID- 11009897
TI - Optimizing organization transitions: Part II.
PMID- 11009899
TI - Employee lawsuits: order in the court.
PMID- 11009898
TI - Help for people with head injuries.
PMID- 11009900
TI - A timely turning.
PMID- 11009901
TI - Do your community benefits have any impact? Part 1.
PMID- 11009902
TI - Hospital staffing in rural areas.
PMID- 11009903
TI - Nursing shortages: insights and solutions.
PMID- 11009904
TI - The declining state of Michigan hospitals.
PMID- 11009905
TI - Beyond fear. Improving documentation enhances compliance, quality and
reimbursement.
PMID- 11009906
TI - Tipping the scales for health care.
PMID- 11009907
TI - Who makes a difference?
PMID- 11009908
TI - Fighting a new war on drugs.
PMID- 11009910
TI - HR budgets could use some lemon-aid.
PMID- 11009909
TI - A new link.
PMID- 11009911
TI - How much space do you really need?
PMID- 11009912
TI - How to stop the pain.
PMID- 11009913
TI - Do your community benefits have impact? Part 2.
PMID- 11009914
TI - Strategic financial management.
PMID- 11009915
TI - How to reduce unemployment liability.
PMID- 11009916
TI - The 6 percent solution.
PMID- 11009917
TI - Safe harbor rules shed new light on surgery center joint ventures.
PMID- 11009918
TI - Perspectives. The wheels of policy grind slowly: top story of 1999 is Medicare
Commission's decision to punt.
PMID- 11009919
TI - Perspectives. Pain Act: for foes and supporters a matter of, first, do no harm.
PMID- 11009920
TI - Marketplace. External reviews of plan decisions: doubts grow along with
acceptance.
PMID- 11009922
TI - Perspectives. HCFA coverage rule: prudent purchasing or bureaucracy run amok?
PMID- 11009921
TI - Perspectives. U.S. spends a lot on health but doesn't know what it buys.
PMID- 11009923
TI - Perspectives. Will we try to manage care again? This time, for drugs?
PMID- 11009924
TI - Marketplace. Why payers like team assessments to gauge quality of behavioral
health care.
PMID- 11009925
TI - Perspectives. Home health PPS spells relief to some, but fate of sickest
uncertain.
PMID- 11009926
TI - Perspectives. High-tech, primary care-oriented, Finland tackles care quality,
choice.
PMID- 11009927
TI - Marketplace. Medicare drug coverage: trying to guess how employers would change
their plans.
PMID- 11009928
TI - Perspectives. Caring for the underserved: it's a tough job and nobody has to do
it.
PMID- 11009929
TI - Perspectives. WellPoint's new plans target uninsured, but scholars are skeptical.
PMID- 11009930
TI - Use 'TRU' (total resource utilization) data to evaluate utilization, disease
costs.
PMID- 11009931
TI - Pennsylvania council uses risk-adjusted hospital data to improve patient care.
PMID- 11009932
TI - Intensive drug therapies contribute to decline in hospital use for HIV.
PMID- 11009933
TI - Most initial medical benefit denials reversed on appeal.
PMID- 11009934
TI - Local medical advisory boards develop stage-specific guidelines to improve
outcomes, cut costs.
PMID- 11009935
TI - HMOs may not screen diabetics adequately for complications related to their
disease.
PMID- 11009936
TI - Hospitals to examine, improve medication safety under new plan to reduce medical
errors.
PMID- 11009937
TI - Updated system enhances patient identification, outcomes analysis; helps manage
risk.
PMID- 11009938
TI - Contract labor use in healthcare.
PMID- 11009939
TI - Relations with news media: perceptions of healthcare executives.
PMID- 11009940
TI - Is education negotiable? A behind-the-scenes look at resident physician
unionization in a competitive business setting.
PMID- 11009941
TI - Acquired Immunodeficiency Syndrome (AIDS) update, Part 1.
PMID- 11009942
TI - Campaign 2000: the candidates and America's health.
PMID- 11009943
TI - Readability and comprehension of the introduction to the Massachusetts Health
Care Proxy.
PMID- 11009944
TI - Ethical decision making in healthcare management.
PMID- 11009945
TI - Decentralization and central and regional coordination of health services: the
case of Switzerland.
AB - As part of reforms in the health care delivery sector, decentralization is
currently promoted in many countries as a means to improve performance and
outcomes of national health care systems. Switzerland is an example of a country
with a long-standing tradition of decentralized organization for many purposes,
including health care delivery. Apart from the few aspects where the
responsibility is at the federal level, it is the task of the 26 cantons to
organize the provision of health services for the population of around 7 million
people. This permits the system to be responsive to local priorities and interest
as well as to new developments in medical and public health know-how. However,
the increasing and complex difficulties of most health care delivery systems
raise questions about the need for mechanisms for coordination at federal level,
as well as about the equity and the effectiveness of the decentralized approach.
The Swiss case shows that in a strongly decentralized system, health policy and
strategy elaboration, as well as coordination mechanisms among the regional
components of the system, are very hard to establish. This situation may lead to
strong regional inequities in the financing of health care as well as to
differences in the distribution of financial, human and material inputs into the
health system. The study of the Swiss health system reveals also that, within a
decentralized framework, the promotion of cost-effective interventions through a
well-balanced approach towards promotional, preventive and curative services, or
towards ambulatory and hospital care, is difficult to achieve, as agreements
between relatively autonomous regions are difficult to obtain. Therefore, a
decentralized system is not necessarily the most equitable and cost-effective way
to deliver health care.
PMID- 11009946
TI - An economic appraisal of alternative strategies for the delivery of MCH-FP
services in urban Dhaka, Bangladesh.
AB - The strategy of distributing maternal and child health and family planning (MCH
FP) services at the doorsteps of the clients--through routine visits to the
eligible couples by trained fieldworkers--has been instrumental in increasing the
contraceptive prevalence rate (CPR), reducing fertility and attaining a
considerably high immunization coverage of children and women in Bangladesh. The
doorstep strategy, however, appeared to be labour-intensive and costly. With the
maturity of the programme, priorities of the national MCH-FP programme have
shifted to a stage that calls for more cost-effective service-delivery
strategies, capable of offering a broader package of reproductive and other
essential health services. The main objective of the present study was to examine
the cost and effectiveness implications of the alternative strategies of
delivering services from fixed sites--field-tested within an ICDDR,B operations
research--in comparison to the conventional (existing) doorstep strategy. The key
findings of the economic appraisal indicated that, at the end of the operations
research intervention, both cost per birth averted and cost per QALY gained were
lowest for the option of delivering services from static (fixed-site) clinics:
US$13 and US$17 compared with the corresponding values of US$18 and US$42 for the
doorstep strategy. Provision of health and family planning services from clinics-
complemented with a reduced system of outreach workers to inform and target the
hard-to-reach clients--was found to be the most cost-effective service-delivery
alternative.
PMID- 11009947
TI - Primary health care ICD--a tool for general practice research.
AB - The International Classification of Diseases (ICD) has become the only diagnostic
classification system of international standard that allows reliable comparisons
of epidemiological data between countries, parts of a country, levels of health
care systems, or different periods of time. However, for primary health care
purposes it is too specific to describe problems relevant to the work of general
practitioners (GPs). Tools are thus needed to 'compress' data in primary health
care for educational, administrative and research purposes. The objective of this
paper was to introduce a diagnosis coding system that can be used in primary
health care settings for these purposes. Principal diagnoses, as assessed by
medical doctors, were collected from 20,648 patient visits. After primary coding,
according to the ICD on a five-digit scale, the diagnoses were grouped into
larger entities, which reduced the number of diagnoses to one eighth of the
original number. The ten most common original five-digit diagnoses accounted for
one quarter of all consultations, whereas the ten most common diagnoses counted
for one half of all consultations after compressing the data into new categories.
Analysing epidemiological data in the records of primary health care by the ICD
offers benefits because of the latter's wide use. These are discussed below.
PMID- 11009948
TI - A question of emphasis: efficiency or equality in the provision of
pharmaceuticals.
AB - The reported results are part of the overall evaluation of the new drug
distribution legislation that went into effect in March 1996, liberalising
ownership of community pharmacies in Iceland. We addressed the following
question: What impact did the legislation have on users' access to and costs of
pharmaceuticals? Seven focus group discussions were conducted with pharmacy
customers in different locations in May, August and October 1997. Widespread
ignorance about the legislation was observed. Pharmacy customers preferred to
discuss the role of physicians in 'irrational drug use' to discussing community
pharmacies. A definite split was observed between urban and rural pharmacy
customers; whereas definite changes were reported in the urban setting (lower
prices and increased access), the rural population's perception is that it is
being left out. Although the study design is not generalisable, it is clear that
the equilibrium between equality and efficiency in pharmaceutical distribution in
Iceland has shifted. The introduction of the free market system has increased
inequality between rural and urban residents in exchange for increased
efficiency.
PMID- 11009949
TI - Analysing the 'new' British National Health Service.
AB - The British National Health Service (NHS) has seen a proliferation of confusing
and sometimes conflicting labels in recent years. It has been claimed that during
the Conservative Government's period of office the 'classic' NHS was
'restructured' and then turned into the 'new' NHS. The New Labour Government of
1997 has claimed that it will deliver a 'new' NHS. If all these claims are
correct, it should be possible to identify four distinct periods, with three
clear 'breaks of slope' with significant changes in important indices on moving
from one label to another. This paper attempts to look behind these labels by
critically examining what has changed in the NHS since 1979. In simple terms,
what has been 'restructured'? What is new about the 'new' NHS? Why are these
changes important? It is concluded that while the NHS has certainly undergone
significant changes in the past 20 years or so, the appearance of a 'new' NHS may
be premature as in many areas it is possible to see the marks of continuity as
well as change, and policy impact is characterised by greater incrementalism than
policy rhetoric.
PMID- 11009951
TI - Hospital survey process changes in 2000.
PMID- 11009950
TI - Integrating outcomes into the accreditation process.
PMID- 11009952
TI - Reducing solid waste in health care organizations.
PMID- 11009953
TI - Sentinel event trends in wrong-site surgery.
PMID- 11009954
TI - Survey process for anesthesia care standards in transition.
PMID- 11009955
TI - Joint Commission mission statement revised to include patient safety.
PMID- 11009956
TI - Changes to dialysis water testing requirements.
PMID- 11009958
TI - Kentucky hospitals sue HHS over disproportionate-share losses tied to definition.
PMID- 11009957
TI - Government releases health advisory on endoscope reprocessing.
PMID- 11009959
TI - Big benefit for benefits. Antitrust concessions help Mont. system post $9 million
profit.
PMID- 11009960
TI - Outlook 2000. Industry turbulence may subside as Medicare pays more and merged
systems look inward....
PMID- 11009961
TI - Calif. law governs not-for-profit sales.
PMID- 11009962
TI - Judge rejects Calif. antitrust challenge.
PMID- 11009963
TI - Native son rises. Chief executive of Albuquerque's Presbyterian Healthcare puts
youthfulness to work.
PMID- 11009964
TI - Cyberspace use in infancy.
PMID- 11009965
TI - Back-office, online.
PMID- 11009966
TI - 'Critical access' revives rural hospitals.
PMID- 11009967
TI - Much at stake in new margin calculation.
PMID- 11009969
TI - Healthcare costs rise in 1998. Annual percentage increase in healthcare spending
since 1993 is at its highest.
PMID- 11009968
TI - N.Y. reform measure fulfills most wishes.
PMID- 11009970
TI - AHA: hospitals get around reporting.
PMID- 11009971
TI - Flunking on charity care.
PMID- 11009972
TI - New England HMOs hit hard.
PMID- 11009973
TI - Mergers & acquisitions. Spinoffs, big deals dominate in '99.
PMID- 11009974
TI - An HMO veteran checks out.
PMID- 11009975
TI - Challenges converge on St. Louis system.
PMID- 11009976
TI - AHA backpedals. Unaware of hospitals' dodging reporting requirements, it says.
PMID- 11009977
TI - Miss. project aimed at resolving issues.
PMID- 11009978
TI - Number of for-profits declined in 1999.
PMID- 11009979
TI - Quality begins in the boardroom.
PMID- 11009980
TI - 2000 Trustees of the Year.
PMID- 11009981
TI - Hospitals' price hikes outpace inflation.
PMID- 11009982
TI - Survey to rank systems on governance.
PMID- 11009983
TI - What's a credit rating worth?
PMID- 11009984
TI - Uncompensated-care spending up a little.
PMID- 11009985
TI - Health system faces tough talk.
PMID- 11009986
TI - Idaho docs planning to take on Columbia.
PMID- 11009987
TI - One thing leads to another. Medical-errors report means money for medical
outcomes research.
PMID- 11009988
TI - Drugmakers shift on Medicare coverage.
PMID- 11009989
TI - It may be politics over policy in 2000.
AB - Thanks to election-year realities, it's likely to be politics over policy on
Capitol Hill in 2000. Congress and the Clinton administration have plenty of
unfinished healthcare business, but with the pressures of the campaign trail,
expect a shortened legislative window of opportunity. While healthcare remains
high on everyone's agenda, the likelihood of compromise remains low.
PMID- 11009990
TI - Nursing homes embrace Internet.
PMID- 11009991
TI - Bond volume slows from 1998 record.
PMID- 11009992
TI - Whopping settlement for Fresenius.
PMID- 11009993
TI - A tale of two COPAs (Certificate of Public Advantage)
PMID- 11009994
TI - Online and public. Neoforma.com, first Internet-based healthcare supplier to
launch IPO, soars in NASDAQ debut.
PMID- 11009995
TI - Panel may support doubling of DRGs.
PMID- 11009996
TI - Outpatient prices jump. Costs rose 6.7%, surpassing increase in prescription
prices.
PMID- 11009997
TI - Attract and retain RNs.
PMID- 11009998
TI - The HIPAA lurks. Just when CIOs thought it was safe for business as usual....
AB - Just when healthcare chief information officers thought it was safe to return to
business as usual, along comes the administrative simplification provisions of
the Health Insurance Portability and Accountability Act of 1996. Those
regulations, which will require providers to reconfigure patient records into an
electronic format, will be anything but simple for hospitals, systems and
insurers.
PMID- 11009999
TI - Top 100 integrated healthcare networks. Intermountain tops list of best systems.
PMID- 11010000
TI - Providers cut losses by selling HMOs.
PMID- 11010002
TI - Hearings look at fixes for medical errors.
PMID- 11010001
TI - Web wise. Leading-edge providers take Internet to its limits.
PMID- 11010003
TI - Dallas PPM company files for Chapter 11.
PMID- 11010004
TI - St. Louis hospital shuts doors again.
PMID- 11010005
TI - West Penn to refinance AHERF debt.
PMID- 11010006
TI - Who was right in Grand Rapids?
PMID- 11010007
TI - CHW to sell Calif. hospital to college.
PMID- 11010008
TI - For-profit chains face long-term challenges.
PMID- 11010009
TI - Going back to the well. AHA kicks off campaign for $25 billion in new BBA
rollbacks.
PMID- 11010010
TI - Mass. Blues posts another strong year.
PMID- 11010012
TI - Vanderbilt's sale of health plans stalls.
PMID- 11010011
TI - Texas health plans change hands.
PMID- 11010013
TI - IHS expansion leads to Chapter 11.
PMID- 11010014
TI - Natural selection. Weaker hospitals find today's climate is a jungle.
AB - Most hospital executives would probably agree that it's a jungle out there. In
today's competitive market, it's survival of the fittest. Some observers say the
healthcare industry's version of Darwinism might not be such a bad thing. The
demise of weaker hospitals thins overcapacity and helps control costs. But others
say it has gone too far, becoming an unhealthy evolution that's not just
winnowing the weak but also bringing down the strong.
PMID- 11010015
TI - Hospital companies come in from the cold.
PMID- 11010016
TI - Wash. insurers must cover alternative care.
PMID- 11010018
TI - First medical errors bill follows hearings.
PMID- 11010017
TI - AHA tries makeover to thwart regulation.
PMID- 11010019
TI - Beverly pays $175 million in fraud case.
PMID- 11010020
TI - Merger now a total split. UCSF Stanford partners end talks on several joint
services.
PMID- 11010021
TI - Private tax-cut plans. Columbia, Tenet push for lower property assessments,
despite community-benefit argument.
AB - The nation's two largest for-profit hospital chains have adopted another cost
cutting strategy: They've hired a small army of consultants and lawyers to
persuade local tax assessors that many of their hospitals are overvalued, so they
should pay less in real estate taxes. But the strategy carries some risk for the
for-profits, which usually cite tax payments as one of their "community
benefits."
PMID- 11010022
TI - Budget dance renewed. Clinton, providers take positions on drugs, reimbursement.
PMID- 11010023
TI - States take lead on quality accountability.
PMID- 11010025
TI - Lobbies in fight over senior drug coverage.
PMID- 11010024
TI - Health Care Hall of Fame 2000.
PMID- 11010026
TI - Protocols reduce errors in Wash. heart program.
PMID- 11010028
TI - Insurers pile on in Fresenius case.
PMID- 11010027
TI - Mass. HMO's fall may rock hospital credits.
PMID- 11010029
TI - NetCare may sell remaining hospitals.
PMID- 11010030
TI - Charter seeks new deal in bankruptcy.
PMID- 11010031
TI - CEO turnover drops to new low.
PMID- 11010032
TI - Columbia looks to cut costs.
PMID- 11010033
TI - Columbia stirs storm over Fla. CON.
PMID- 11010034
TI - PHS to close Ohio teaching hospital.
PMID- 11010035
TI - Tax increase funds hospital takeover.
PMID- 11010036
TI - Digital mammography system OK'd by FDA.
PMID- 11010037
TI - Device group: fees exceed limit.
PMID- 11010038
TI - The great consolidator. Healtheon/WebMD keeps on buying in its bid to dominate
online health information.
PMID- 11010039
TI - Elbows fly in medical-errors game.
PMID- 11010040
TI - Training shouldn't be first to go. Hospitals, health systems put quality,
profitability at risk by slashing spending on staff education.
PMID- 11010041
TI - Takingabigrisk.com. Execs chuck high-powered hospital jobs for e-venture.
AB - Impatient with the industry's slow transition to quality improvement, an unusual
group of former healthcare executives--including a canine deputy--is trying to
establish a high-powered Internet venture from bargain-basement digs. The
entrepreneurs, with visions of an IPO dancing in their heads, want to give
providers and patients access to the information they need to improve health
outcomes.
PMID- 11010042
TI - Bond market changes for Tennessee system.
PMID- 11010043
TI - Lobbying firm gets pork for hospitals.
PMID- 11010044
TI - AMA in a $20 million hole.
PMID- 11010046
TI - 'Catching' the fat bug. Can obesity be caused by exposure to a virus?
PMID- 11010045
TI - The signature of death. Reviving the lost art of autopsy could be a boon for the
living.
PMID- 11010047
TI - Living with diabetes is getting easier--and a cure could be on the way.
PMID- 11010048
TI - Positive on testing. But will the Olympic Games get clean this year--or ever?
PMID- 11010049
TI - Taking aim at the citadels of slime. Bacterial 'cities' offer new insights into
disease.
PMID- 11010050
TI - Carcinoma renegades. Why do tumors spread?
PMID- 11010051
TI - Backyard paintball play leads to serious eye injuries.
PMID- 11010052
TI - Holey bike seats! You won't believe what cycling could do to you.
PMID- 11010053
TI - When weak knees are the bane of strong women, special exercises help.
PMID- 11010054
TI - Treatment of recurrent respiratory tract infections with a polyvalent bacterial
lysate: results of an open, prospective, multinational study.
AB - This multicenter, open study, carried out in 14 countries in Europe, Latin
America, and Asia, recruited 4965 patients suffering from recurrent respiratory
tract infections to investigate the safety and acceptability of the oral
bacterial lysate immunomodulator LW 50020. Patients remained in the study for 4
months (two 4-week courses of LW 50020 separated by a 28-day treatment-free
interval and follow-up). The incidence of all adverse events was 7.2%; that of
adverse drug reactions was 0.6%. Adverse drug reactions were mild to moderate and
not more frequent in the large subgroup of patients (77%) with a known history of
allergies or underlying respiratory diseases; however, the incidence of adverse
events in this subgroup was twofold higher than in the study population as a
whole, probably indicating a generally increased vulnerability to disease. No
clinically relevant changes in laboratory variables followed treatment.
Comparison of the first study period (first course of LW 50020 and drug-free
interval) with the second study period (second course of LW 50020 and follow-up)
showed an overall reduction of at least 50% in the number, severity, and duration
of respiratory tract infections, the number of antibiotic and symptomatic
treatments, and the number of days absent from school or work. Tolerability and
acceptability were assessed as good or very good in 99% of patients who completed
the study.
PMID- 11010055
TI - Use of ambulatory blood pressure monitoring to compare antihypertensive efficacy
and safety of two angiotensin II receptor antagonists, losartan and valsartan.
Losartan Trial Investigators.
AB - The efficacy and safety of losartan and valsartan were evaluated in a
multicenter, double-blind, randomized trial in patients with mild to moderate
essential hypertension. Blood pressure responses to once-daily treatment with
either losartan 50 mg (n = 93) or valsartan 80 mg (n = 94) for 6 weeks were
assessed through measurements taken in the clinic and by 24-hour ambulatory blood
pressure monitoring (ABPM). Both drugs significantly reduced clinic sitting
systolic (SiSBP) and diastolic blood pressure (SiDBP) at 2, 4, and 6 weeks.
Maximum reductions from baseline in SiSBP and SiDBP on 24-hour ABPM were also
significant with the two treatments. The reduction in blood pressure was more
consistent across patients in the losartan group, as indicated by a numerically
smaller variability in change from baseline on all ABPM measures, which achieved
significance at peak (P = .017) and during the day (P = .002). In addition, the
numerically larger smoothness index with losartan suggested a more homogeneous
antihypertensive effect throughout the 24-hour dosing interval. The
antihypertensive response rate was 54% with losartan and 46% with valsartan.
Three days after discontinuation of therapy, SiDBP remained below baseline in 73%
of losartan and 63% of valsartan patients. Both agents were generally well
tolerated. Losartan, but not valsartan, significantly decreased serum uric acid
an average 0.4 mg/dL at week 6. In conclusion, once-daily losartan 50 mg and
valsartan 80 mg had similar antihypertensive effects in patients with mild to
moderate essential hypertension. Losartan produced a more consistent blood
pressure-lowering response and significantly lowered uric acid, suggesting
potentially meaningful differences between these two A II receptor antagonists.
PMID- 11010056
TI - Spine fusion for discogenic low back pain: outcomes in patients treated with or
without pulsed electromagnetic field stimulation.
AB - Sixty-one randomly selected patients who underwent lumbar fusion surgeries for
discogenic low back pain between 1987 and 1994 were retrospectively studied. All
patients had failed to respond to preoperative conservative treatments. Forty-two
patients received adjunctive therapy with pulsed electromagnetic field (PEMF)
stimulation, and 19 patients received no electrical stimulation of any kind.
Average follow-up time was 15.6 months postoperatively. Fusion succeeded in 97.6%
of the PEMF group and in 52.6% of the unstimulated group (P < .001). The observed
agreement between clinical and radiographic outcome was 75%. The use of PEMF
stimulation enhances bony bridging in lumbar spinal fusions. Successful fusion
underlies a good clinical outcome in patients with discogenic low back pain.
PMID- 11010057
TI - A case of chronic adrenocortical insufficiency with iatrogenic anasarca.
AB - The decrease in active hormones that characterizes chronic adrenal insufficiency
results in hypovolemia. In some patients, residual adrenal function,
mineralocorticoid therapy, and concomitant heart or liver failure, or both, can
paradoxically provoke edema. The case report that follows describes a patient
with iatrogenically induced anasarca resulting from the unhappy confluence of
usually appropriate therapy and coexisting medical conditions.
PMID- 11010058
TI - Managing chronic nonmalignant pain: overcoming obstacles to the use of opioids.
AB - Physicians involved in cancer pain management treat thousands of patients with
opioids, whose effective analgesia improves overall functioning. Side effects
generally are tolerable, and treatment can be maintained with stable doses for
long periods. Problems with addiction are infrequent. Many physicians, however,
assume that opioids should be used only for chronic malignant pain. Research and
clinical experience have demonstrated that opioids can safely and effectively
relieve most chronic moderate to severe nonmalignant pain. Fears of addiction,
disciplinary action, and adverse effects result in ineffective pain management.
With current information on the use of opioids in chronic nonmalignant pain,
primary care physicians can overcome these obstacles. Guidelines must clearly
define the role of the primary care physician in the proper management of pain
and the integration of opioid therapy. Used appropriately, opioids may represent
the only source of relief for many patients.
PMID- 11010059
TI - A new look at dry eye disease and its treatment.
AB - This review examines the impact of moderate to severe dry eye disease on daily
life and medical-resource utilization. The results suggest that current treatment
paradigms can lead to unacceptable costs in both quality of life and progressive
use of healthcare resources. Evidence linking this disease to T-cell-mediated
inflammatory processes lays the foundation for understanding the clinical
benefits of topical cyclosporine, an immunomodulatory and anti-inflammatory
agent.
PMID- 11010060
TI - Efficacy and safety of ketorolac tromethamine 0.5% and levocabastine 0.05%: a
multicenter comparison in patients with seasonal allergic conjunctivitis.
AB - This multicenter, double-masked, randomized, parallel-group study compared the
efficacy and safety of ketorolac tromethamine 0.5% ophthalmic solution with
levocabastine 0.05% and ketorolac tromethamine vehicle in patients with seasonal
allergic conjunctivitis. One drop of ketorolac, levocabastine, or vehicle was
instilled in each eye four times daily for 6 weeks. In the majority of efficacy
variables, ketorolac produced the greatest improvements, followed by
levocabastine and vehicle. Ketorolac was significantly more effective (P < .05)
than vehicle in reducing mean itching scores, palpebral hyperemia, bulbar
hyperemia, and edema. Patients treated with ketorolac reported significant
improvements (P < .05) in their ability to sleep and to concentrate on work,
compared with those who received vehicle. No significant differences were noted
among the treatment groups in safety or tolerability. Ketorolac tromethamine 0.5%
ophthalmic solution instilled four times daily is effective and safe in reducing
the signs and symptoms of seasonal allergic conjunctivitis.
PMID- 11010061
TI - Secondary health conditions among middle-aged individuals with chronic physical
disabilities: implications for unmet needs for services.
AB - Data from the Aging with Disability (AwD) Study are used to examine variations in
the types and frequency of secondary conditions experienced by 301 middle-aged
individuals living with the effects of three disabling conditions: polio (n =
124), rheumatoid arthritis (RA) (n = 103), and stroke (n = 75). All respondents
were randomly selected from a county rehabilitation hospital or a community-based
subject pool. Secondary conditions are operationalized as (1) the number of new
health problems diagnosed or treated since the onset of the primary disability
and (2) the amount of change/decline in basic and instrumental daily activities
since a previous reference period in the disability trajectory. Also analyzed are
changes in use of assistive devices and unmet needs for services. Differences in
secondary conditions are examined within the AwD sample by impairment group and
between samples by comparing AwD rates to national estimates for the same cohort.
Results reveal significant differences in the types of new health problems
reported by persons living with polio, RA, and stroke and document marked
disparities, or accelerated aging, between disabled and nondisabled adults.
Findings are discussed in terms of the changing health care needs of persons
aging with disability and the importance of improving access to preventive
services, ongoing rehabilitation, and assistive technology.
PMID- 11010062
TI - Functional changes in persons aging with spinal cord injury.
AB - Declines in general physical function and the effect of these changes on
activities of daily living and needs for assistance were assessed in 150
individuals with spinal cord injury (SCI). The sample consisted of outpatients
returning for follow-up at the spinal cord injury clinic at Rancho Los Amigos
National Rehabilitation Center in Downey, CA. The average duration of injury of
the sample was 13 years (range 1-37), and average age was 38 years (range 18-64).
Twenty-four percent of those sampled experienced a decline or change in their
physical function within the last 5 years. Individuals experiencing declines were
significantly older than those without changes, averaging 45 years versus 36
years. The group with change also had a longer duration of injury, averaging 18
years versus 11 years compared to the group reporting no declines. Fatigue was
the most frequently reported problem, followed by pain and weakness. Over half of
the group with changes required additional assistance with activities of daily
living (ADLs). Family members were the primary helpers for both ADLs and
instrumental activities of daily living (IADLs) for those persons experiencing
changes. The use of assistive technology, primarily equipment for bathing,
toileting, and low technology devices, increased with time. The increased
vulnerability to loss of function in persons with advancing age and duration of
injury in this population with SCI suggests the need for early preventative
measures, routine assessments to detect changes, and access to health care and
supportive services to alleviate or minimize the effect of these changes.
PMID- 11010063
TI - Expectations of health, independence, and quality of life among aging spinal cord
injured adults.
AB - While our understanding of aging and mortality in spinal cord injury is evolving,
precise estimates are still not available to assist people with spinal cord
injuries in knowing what to expect as they grow older. The work of a number of
authors suggests that the life expectancy of those with spinal cord injuries is
improving. However, little is known about the conditions in which individuals may
expect to spend their remaining years of life. This study used information from a
50-year database on spinal cord injury, in combination with national mortality
statistics and new survey information, to estimate the number of remaining years
that individuals could expect to spend in a variety of states of health,
independence, and quality of life. The study showed that expectations of health
are similar to those found in the general population. Regardless of total life
expectancy, individuals could expect to spend about six of their remaining years
in poor health, presumably near the end of life. Expectations of independence
varied depending on lesion level. Those with paraplegia became less independent
over time, moving from complete to modified independence. Those with quadriplegia
appeared to have a greater expectation of independence over time; however, in
actuality, only those who were most independent survived to report outcomes at
older ages. Expectations of quality of life remained high until the fifth decade
postinjury.
PMID- 11010064
TI - Work problems and accommodations reported by persons who are postpolio or have a
spinal cord injury.
AB - A number of studies have documented early functional declines in persons with a
disability. The purpose of this study was to document (1) whether employees who
are aging with their disability have experienced new work problems as a
consequence of functional declines and (2) whether their work problems are being
accommodated adequately. Ninety-six individuals with a disability (50 who are
postpolio and 46 who had a spinal cord injury) were interviewed by phone. Each
had worked at least 5 years postonset and was either currently working or
unemployed for less than 5 years at the time of the interview. Forty-nine of the
50 persons who are postpolio reported they had experienced functional declines in
recent years, and 41 of the 50 rated the severity of their disability greater
than it was when they first began working. As a result of the functional declines
they had experienced, most (90.9%) of their work problems were new and would not
have been significant problems for them when they first began working. The
situation was very different for the group with spinal cord injuries. Only a few
members of that group had experienced functional declines that were causing new
problems at work. A total of 480 work problems were reported by study
participants. Three out of every eight problems did not have an accommodation
satisfactory to the employee. The primary reason why a satisfactory solution was
not provided was that no accommodation had been identified. Employers were
generally supportive of the employee's need for accommodation; they paid for
59.1% of the accommodations that had a cost and refused to provide an
accommodation for only 18 of the 480 problems.
PMID- 11010065
TI - Quality of life while aging with a disability.
AB - Being able to develop or maintain a positive, or high, quality of life (QOL)
after a disability is one of the most important outcomes from rehabilitation.
Negative, or low, QOL may also occur, especially when people return to the
community. Furthermore, as people with disability age, many experience changes in
their health and functioning that challenge their hard-won QOL. This article
describes research on QOL among persons who are aging with a disability. Both
positive and negative dimensions of QOL were studied. Being able to maintain
community activities was significantly related to QOL. Current age and age at
onset of disability played a nonsignificant role on negative QOL but were
significantly related to positive QOL. Assistive technology can play a
significant role in helping individuals who are aging with a disability to
maintain valued activities and experiences.
PMID- 11010066
TI - Field of assistive and rehabilitation technology.
PMID- 11010067
TI - Introduction. The importance of aging with a disability to assistive technology.
PMID- 11010068
TI - Aging with a disability: views from the National Institute on Disability and
Rehabilitation Research.
AB - As I move toward the completion of my term as Director of the National Institute
on Disability and Rehabilitation Research (NIDRR), I see many examples of renewal
in our field. For example, disability studies and rehabilitation science are
emerging new areas of academic specialization, and we will all be involved in
shaping the future of these endeavors. The field is recapturing its identity and
relevance locally and internationally. Also, I see a considerable number of
challenges that range from acute care in medical rehabilitation to universal
design in engineering to overall technology policy. I see a challenge in moving
research to practice, a challenge in funding, a challenge in service delivery
locations, and a challenge in defining the role of the professional in order to
build capacity for the future. I believe that the research field ignores practice
at its own peril, including practice in older fields such as vocational
rehabilitation and in newer fields such as cognitive science and access
engineering. Practice must be determined by today's needs and those we foresee
for tomorrow. For the NIDRR family, the Long-Range Plan provides a beacon to
direct us into the new millennium.
PMID- 11010069
TI - Metabolic and endocrine changes in persons aging with spinal cord injury.
AB - Persons with spinal cord injury (SCI) have secondary medical disabilities that
impair their ability to function. With paralysis, dramatic deleterious changes in
body composition occur acutely with further adverse changes ensuing with
increasing duration of injury. Lean mass, composed of skeletal muscle and bone,
is lost and adiposity is relatively increased. The body composition changes may
be further exacerbated by associated reductions in anabolic hormones,
testosterone, and growth hormone. Individuals with SCI also have decreased levels
of activity. These body composition and activity changes are associated with
insulin resistance, disorders in carbohydrate and lipid metabolism, and may be
associated with premature cardiovascular disease. Although limited information is
available, upper body exercise and cycle ergometry of the lower extremities by
functional electrical stimulation (FES) have been reported to have a salutary
effect on these body composition and metabolic sequelae of paralysis. Perhaps
other innovative, externally mediated forms of active exercise of the paralyzed
extremities will result in an increased functional capacity, metabolic
improvement, and reduction of atherosclerotic vascular disease.
PMID- 11010070
TI - Medical problems in adults with cerebral palsy: case examples.
AB - The United Cerebral Palsy Association estimates that there are approximately one
half million adults with cerebral palsy in the United States. The number may be
growing due to advances in medical care and the increased life expectancy of
adults in general. Little has been published regarding their medical issues and
rehabilitation needs. What little has been published has indicated almost a total
neglect of specialty care and preventive medical services. Five case examples are
presented to help illustrate particular medical and surgical problems not
identified by either pediatric or adult healthcare providers alone. Each
individual shows improvement with comprehensive team-oriented specialty care.
Further study is encouraged.
PMID- 11010071
TI - The family resemblance metaphor: some unfinished business of interpretive
inquiry.
AB - The rapidly expanding discipline of interpretive inquiry, especially in its
narrative analysis form, has not been fully cognizant of certain crucial
epistemological and methodological assumptions that form the ultimate basis of
its purpose. Even after abandoning traditional positivist views, the related
disciplines within the human sciences that are engaged in interpretive inquiry
have still not discovered the core implicit assumptions that militate against a
full acceptance of this form of inquiry. This article outlines the locus of these
implicit assumptions and then argues that the legitimacy of these enterprises
must be grounded in a well-known but heretofore undiscovered perspective, namely,
Wittgenstein's notion of a family resemblance. It is argued that this metaphoric
phrase is the key to unlocking the real and unique nature of narrative analysis.
PMID- 11010072
TI - The church family and kin: an older rural black woman's support network and
preferences for care providers.
AB - Although kin and church are considered premier support sources for rural elders,
few scholars have undertaken descriptive studies to explore the nature of rural
Black elders' support networks and their preferences for in-home service
providers. In the case study described in this article, methods of support
network analysis and descriptive phenomenology were used to analyze data from
five lengthy, open-ended interviews with a 94-year-old rural Black woman. The
various groups and individuals of her network are labeled in her words, the
network's supportive functions are described, and preferences for providers are
noted. In addition, the varying structures of her home care experience with the
support network members are described. Her attempts to voice and exercise her
preferences for in-home service providers are explained in terms of two
contrasting processes: preference uptake and preference suppression. Based on
these findings, implications for appraising the appropriateness of rural elders'
in-home services are discussed.
PMID- 11010073
TI - Cross-cultural comparison of health perceptions, concerns, and coping strategies
among Asian and Pacific Islander American elders.
AB - This article compares the health perceptions, concerns, and coping strategies
among elders in two Asian and Pacific Islander American communities. The
qualitative comparison is conducted between elder Chamorros of Guam and elder
Chinese of the United States, using a focused ethnography for data collection and
the grounded theory method for cross-cultural analysis. The health perceptions of
these two communities are manifest in two themes: (a) a sense of holism among
body, mind, and spirit and (b) an orientation toward others. The health concerns
of these two communities include universal experiences of aging, structural
elements within the American health care system, and cultural changes impacting
health. A significant coping strategy is adaptation to changes while maintaining
continuity. Finally, implications for the delivery of culturally appropriate
health care services to Asian and Pacific Islander American elders are discussed.
PMID- 11010074
TI - Physician views on practicing professionalism in the corporate age.
AB - Arnold Relman argues that medical education does not prepare students and
residents to practice their profession in today's corporate health care system.
Corporate health care administrators agree: Physicians enter the workforce
unskilled in contract negotiation, evidence-based medicine, navigating
bureaucratic systems, and so forth. What about practicing physicians? Do they
agree as well? According to this study, they do. Feeling like decentered double
agents and unprepared, physicians find themselves professionally lost, struggling
to balance issues of cost and care and expressing lots of negativity toward the
cultures of medicine and managed care. However, physicians are resilient. A group
of physicians, who may be called proactive, are meeting the professional demands
of corporate health care by becoming sophisticated about its bureaucratic
organization and the ways in which their professional and personal commitments
fit within the system. Following the lead of proactive physicians, the authors
support Relman's thesis and education for both students and physicians requires a
major overhaul.
PMID- 11010075
TI - Visualism in community nursing: implications for telephone work with service
users.
AB - This article explores the potential effects of visualism (a prejudice in favor of
the seen) on the perceived legitimacy of telephone work in community nursing. It
discusses data from an exploratory study on telephone work, which used guided
interviews with a purposive sample of 14 community nurses. Interviewees expressed
both positive and negative ideas about telephone work and had particular concerns
about the assessment of people, context, problems, and comprehension by
telephone. These issues are discussed with reference to publications on
visualism, metaphor, communication, and nursing work. The authors conclude that
an awareness of the possible effects of visualism on ideas and practice could
lead to improvements in both communication and assessment, whether carried out by
telephone or face to face.
PMID- 11010076
TI - Warnings about vulnerability in clients with diabetes and hypertension.
AB - The purpose of the grounded theory study discussed in this article was to
discover and explicate the basic social problem in clients with diabetes and
hypertension that affects their adherence to health care directives. In-depth
interviews with 21 clients with both diabetes and hypertension and 3 health care
providers who care for such clients were concurrently conducted, coded, and
analyzed according to the grounded theory method. Clients with diabetes and
hypertension described being bombarded repeatedly with warnings about their
vulnerability. The warnings were both external (coming from health care
providers, family, and friends) and internal (coming from within themselves).
Internal warnings were discovered to be far more influential in affecting
adherence. This discovery can be used to shape health care providers' social
interactions and treatment plan strategies with clients with diabetes and
hypertension.
PMID- 11010077
TI - Researching illness and injury: methodological considerations.
AB - Circumstances surrounding the physical condition of the critically ill, the
injured, and the dying make the conduct of qualitative research particularly
difficult. Assumptions embedded in qualitative research are challenged or no
longer apply: As sick people, participants are unfamiliar with their everyday
worlds, and they are often incapable of describing their conditions and
perceptions, so that researchers have difficulty obtaining data to comprehend,
interpret, and generally conduct their research. Methodological problems
extending from the participants' condition include the lack of everyday language
to describe their experiences, the instability of the participants' reality, and
the instability of the self. When researching participants who are sick, these
methodological problems result in decisions about the timing of data collection,
challenges to validity and reliability, and debates about who should be
conducting this research.
PMID- 11010078
TI - The unsolicited diary as a qualitative research tool for advanced research
capacity in the field of health and illness.
AB - In this article, the place of diary method is examined in the context of
qualitative tools. Although much neglected in qualitative methodology, there is
considerable support for its use, and it is argued that unsolicited diary
analysis as a qualitative tool has value as a social research method. Although it
is commissioned or solicited diaries that are increasingly popular in health
research, different kinds of diary usage are examined together with certain
possible biases and weaknesses. Although framework analysis was originally
developed for analyzing interview data, it is seen as an appropriate qualitative
tool for the analysis of unsolicited diaries. The analysis of an unsolicited
diary account of a patient suffering from cancer of the larynx is explored as a
potential data source.
PMID- 11010079
TI - The utility of sentinel node biopsy in managing melanoma.
PMID- 11010080
TI - Acne therapy. An expanding arsenal offers relief and cosmesis.
PMID- 11010081
TI - Managing minor closed head injury in children.
PMID- 11010082
TI - Brain injuries in athletics. Assessment and management to prevent a catastrophic
outcome.
PMID- 11010083
TI - Warts and children: can they be separated?
PMID- 11010084
TI - IHC eyes E-health Code of Ethics.
PMID- 11010085
TI - Embarking on a compliance career.
PMID- 11010086
TI - "Dog tags" make data storage easier.
PMID- 11010087
TI - Enhance your organization's awareness of HIPAA.
PMID- 11010089
TI - Compliance across the continuum: what works. Compliance on a shoestring: one
hospice's approach.
PMID- 11010088
TI - Compliance across the continuum: what works. New directions for long-term care.
PMID- 11010090
TI - Compliance across the continuum: what works. Communication is key to home health
compliance.
PMID- 11010091
TI - Comparing the OIG guidances.
PMID- 11010092
TI - Compliance efforts lead to process improvements.
AB - After Medicare regulations and the accompanying paperwork threatened to overwhelm
an outpatient rehabilitation center, staff took steps to simplify the
recertification process. The result was improved efficiency plus increased
commitment to the electronic medical record. Here's how they did it.
PMID- 11010093
TI - Keys to auditing hospital and professional fee coding.
AB - A good audit program can save a provider from sanctions or fines. Whether you
work on the hospital or physician side, here are some tips for better auditing
practices.
PMID- 11010094
TI - Four critical steps to choosing an auditor.
PMID- 11010095
TI - Who answers the medical necessity question?
PMID- 11010096
TI - Ensuring safety and security in a home office.
PMID- 11010097
TI - How to write an effective resume.
PMID- 11010098
TI - Practice brief. Issue: storage media for health information. AHIMA. American
Health Information Management Association.
PMID- 11010099
TI - How to code symptoms and definitive diagnoses.
PMID- 11010100
TI - Understanding the complexities of coding for mental disorders.
PMID- 11010101
TI - Outpatient prospective payment becomes a reality.
PMID- 11010102
TI - Rising to the task.
PMID- 11010103
TI - Understanding HIPAA's transaction and code set standards. American Health
Information Management Association.
PMID- 11010104
TI - Documentation errors result in Medicare overpayment.
PMID- 11010105
TI - Three steps to increasing employee information security awareness.
PMID- 11010106
TI - APCs: a special report. Preparing for the outpatient prospective payment system.
PMID- 11010107
TI - APCs: a special report. Making a proactive transition to APCs.
PMID- 11010108
TI - Strategies for reducing medical errors: HIM's role.
PMID- 11010109
TI - Dialysis settings offer diverse opportunities.
PMID- 11010110
TI - Building a one-stop shop for ideas.
PMID- 11010111
TI - Setting the standard in assisted living.
PMID- 11010112
TI - Practice brief. Letters of agreement/contracts. American Health Information
Management Association.
PMID- 11010113
TI - Surviving and thriving during contract negotiations.
PMID- 11010114
TI - Coding for APCs: case studies.
PMID- 11010115
TI - Confronting educational challenges: lead, follow, or get out of the way.
PMID- 11010116
TI - Improving coding for right heart catheterization.
PMID- 11010117
TI - A dot-com coder.
PMID- 11010118
TI - Retirement plans, personal saving, and saving adequacy.
AB - This Issue Brief addresses three questions raised by recent trends in personal
saving: How are national savings measured and what is the meaning of the trends
in measured personal saving rates, given what is included and what is not
included in those measures? What is the effect of retirement saving programs--in
particular, 401(k) plans and individual retirement accounts (IRAs)--on personal
saving levels? What are the implications of existing saving behavior for the
retirement income security of today's workers? The National Income and Product
Accounts (NIPA), the most commonly referenced gauge of personal saving, is a
widely misunderstood measure. One could argue that a complete measure of saving
would include increases in wealth through capital gains, but NIPA does not factor
accrued and realized capital gains on stocks and other assets into the saving
rate. By one measure, accounting for capital gains results in an aggregate
personal saving rate of 33 percent--more than double the rate of four decades
ago. A major policy question is the impact of tax-qualified retirement saving
plans (i.e., IRAs and 401(k) plans) on personal saving rates. Empirical analysis
of this issue is extremely challenging and findings have been contradictory.
These programs now represent an enormous store of retirement-earmarked wealth in
tax-deferred vehicles: Combined, such tax-deferred retirement accounts currently
have assets of about $4 trillion. Ninety percent of IRA contributions are now the
result of "rollovers" as employees leave employer plans, like 401(k) plans. While
leakage from the system remains a challenge, the majority of the assets in the
system can be expected to be available to fund workers' retirements. One could
argue that, from a retirement income security perspective, workers in general are
better off because IRA and 401(k) programs exist. Surely, many of the dollars in
these programs would have been saved even without the programs; but they would
not necessarily have been earmarked for retirement and been available to fund
retirement expenses. As rollovers become larger, this "partnership" of employment
based qualified plans and IRAs will grow even more important. The evidence
indicates that many groups of American workers appear unlikely to be able to
afford a retirement that maintains their current lifestyle (at least not without
working more years than currently planned). Consensus does not exist on how many
workers are at risk or the typical magnitude of their retirement saving
shortfall. There is a consensus, however, that a substantial number of
individuals are at risk. This is not surprising--despite the fact that the 70
percent of workers are saving for retirement--since relatively few workers know
how much it is that they need to accumulate to fund their retirement.
PMID- 11010119
TI - Employer-sponsored long-term care insurance: best practices for increasing
sponsorship.
AB - Behind the enthusiasm of policymakers for long-term care (LTC) insurance is the
belief that increased ownership of private LTC insurance will reduce the
government's future liability for financing the nation's LTC needs, currently
projected by the Congressional Budget Office to increase by 2.6 percent annually
between 2000 and 2040. Some observers say that sustained economic growth could
keep these increased expenditures at the same share of total GDP; others argue
that current federal expenditure trends will become unsustainable without large
tax increases. The potential of the employer-sponsored group LTC market to stave
off a national LTC financing crisis has recently started to receive popular
notice in the news media. However, for the potential of the group LTC market to
be realized, there must be widespread employer sponsorship of group LTC plans and
significant participation levels among eligible employees in these plans. The
present analysis of industry data estimates the LTC plan sponsorship rate for all
U.S. employers with 10 or more employees at 0.2 percent. The sponsorship rate
among large employers is significantly higher (8.7 percent). The greatest growth
opportunities are projected to lie in the smaller employer market, because it is
enormous and virtually untapped. Nonsponsors cite a variety of barriers to
employer sponsorship of LTC plans. For many nonsponsors, the most important
obstacles are the intrinsic characteristics of their work forces: employees are
too young, transient, part-time, and/or low-income to be suitable for LTC
insurance. For many others, lack of awareness and low priority are the primary
obstacles. Because group LTC insurance has been widely available for only 10
years, many benefits managers view it as "too new and untested." Prior to the
passage of the Health Insurance Portability and Accountability Act (HIPAA), in
August 1996, the tax treatment of long-term care insurance premiums was unclear
because Congress had not addressed the issue and the Internal Revenue Service had
not issued clear guidance. In essence, HIPAA served to clarify the tax status of
LTC insurance and establish product criteria for tax qualification. The
interventions contained in HIPAA appear to have been insufficient to stimulate
coverage growth rates that will meaningfully reduced the future burden on
government financing of LTC. Although employment-based LTC insurance appears to
be the best mechanism for mass expansion of coverage at affordable rates, the
data suggest that employer sponsorship of LTC plans is relatively rare,
especially among smaller employers, and that sponsorship rates may not
dramatically increase without significant investments in employer education and
new incentives.
PMID- 11010120
TI - Voluntary long-term care insurance: best practices for increasing employee
participation.
AB - This is the second of two Issue Briefs (April and May 2000) on long-term care
(LTC) insurance. The previous Issue Brief addressed the problem of increasing
sponsorship, while this report addresses the issue of increasing employee
participation. Participation rates in group LTC insurance plans tend to be low. A
potential watershed event for the development of the employment-based group LTC
market is the proposed LTC program for federal employees and retirees (a program
that would have to be enacted by Congress). The perception of a successful
offering to federal employees could provide an enormous boost to the group LTC
insurance market. Employee communication and education are seen as critical to
the success of LTC enrollments. The importance of support shown by an employer
for a new LTC plan offering cannot be overstated. Unlike 401(k) plan
participation trends, LTC participation rates are highest among large companies.
Insurers tend to view the 40-60 age range as the primary target for group LTC
insurance, and employee salary as the best predictor of LTC insurance enrollment.
Higher educational levels also are associated with higher levels of LTC
participation. Perceived need for LTC insurance is perhaps the biggest barrier to
the purchase of LTC insurance by employees due to competing financial priorities
and the fact that LTC issues are generally off the "radar screens" of younger
employees. Plans with skilled nursing home and home care benefits experience
higher participation rates than plans lacking these benefits. The availability of
lower-cost and long duration benefit options can be an important factor in
determining participation. Most sponsors have chosen to offer noncontributory
(i.e., fully employee-paid) LTC plans. Employer reluctance to make contributions
may be caused by HIPAA's prohibition on the inclusion of LTC insurance in
cafeteria plans. One of the major advantages of group LTC plans is the
availability of guaranteed issue (i.e., issuing coverage without requiring
evidence of insurability) for employees, which is not available in the individual
LTC market. It is easy for enrollment to be derailed by the presence of any of a
number of harmful conditions, such as employer-sponsors who distance themselves
from the offer, ineffective communications, or difficult enrollment processes.
Achieving consistently strong levels of participation in LTC plans will require
employer-sponsors and their insurance carriers to form strong partnerships, with
worker participation as their primary stated goal.
PMID- 11010121
TI - Personal account retirement plans: an analysis of the survey of consumers
finances.
AB - This report is based on data from the Federal Reserve Board's triennial Survey of
Consumer Financies (SCF), which provides the most comprehensive data available on
the wealth of American households. The most recent SCF data are for 1998, and
this report tracks information from the 1992, 1995, and 1998 surveys. The
percentage of families with a participant in a pension plan from a current job
increased from 38.8 percent to 41.0 percent over this six-year period. If one
focuses exclusively on those families with a worker and in which the head is
under age 65, the percentage for 1998 increases to 56.8 percent. The previously
documented trend toward defined contribution plans was confirmed and the
significance of 401(k)-type plans for those families participating in a pension
plan more than doubled, from 31.6 percent in 1992 to 64.3 percent in 1998. The
percentage of family heads eligible to participate in a defined contribution plan
that did so increased from 73.8 percent in 1995 to 77.3 percent in 1998. Of those
families choosing not to participate in a defined contribution plan, 40.3 percent
were already participating in a defined benefit plan. Overall, "personal account
plans" represented nearly one-half (49.5 percent) of all the financial assets for
those families with either a defined contribution plan account, IRA, or Keogh, in
1998. This was a significant increase from 43.6 percent in 1992. The average
total account balance in personal account plans for families with a plan in 1998
was $78,417, an increase of 54 percent in real terms over the 1992 balance of
$50,914 (expressed in 1998 dollars). For families participating in a defined
contribution plan, IRA, or Keogh in 1998, 52 percent of the overall average was
attributed to IRA/Keogh balances (43 percent from IRAs alone), and 44 percent of
the average was from account balances in defined contribution plans with the
current employer. There is a marked tendency for lower-income families to have
larger percentages of their total personal account plan retirement portfolio in
IRAs, although this trend appears to be fading with time. The impact of rollovers
on the average total account balance for all individual account balances appears
to be quite large: $152,451 for those with at least one rollover, versus $78,471
for all families participating in at least one personal account plan, regardless
of whether they have had a rollover. The vast majority of the rollovers would
appear to be going to IRAs, as opposed to a defined contribution plan with a new
employer.
PMID- 11010122
TI - Physician awareness and screening for fetal alcohol syndrome.
AB - This study is concerned with physicians' consistency, aggressiveness, and
perception of importance in screening children for Fetal Alcohol Syndrome (FAS).
Although irreversible, early intervention can improve an affected infant's
survival and success in developing to his/her best potential. This study surveyed
obstetricians. Pediatricians, family and general practitioners in San Antonio,
Texas in 1993 and asked them to express their perceptions of the factors most
important in FAS births. They also responded to questions about the rank of
importance of FAS compared to other congenital disorders and indicated that
alcoholism was the most influential factor in FAS births and that FAS was the
third most common congenital disorder among their pediatric patients. The study
further explored the physicians' clinical method to screen for FAS and their
estimates of how many of their colleagues evaluate their patients for the
syndrome.
PMID- 11010123
TI - Principal-agent theory: a framework for improving health care reform in
Tennessee.
AB - Using a framework based on principal-agent theory, this study examines problems
faced by managed care organizations (MCOs) and major health care providers under
the state of Tennessee's current capitation-based managed care programs called
TennCare. Based on agency theory, the study proposes a framework to show how an
effective collaborative relationship can be forged between the state of Tennessee
and participating MCOs which takes into account the major concerns of third-party
health care providers. The proposed framework further enhances realization of the
state's key health care reform goals which are to control the rising costs of
health care delivery and to expand health care coverage to uninsured and
underinsured Tennesseans.
PMID- 11010124
TI - Impact of health system factors on changes in human resource and expenditures
levels in OECD countries.
AB - In order to gain further insight into the system factors responsible for changes
in the health workforce, this study undertook an empirical examination of the
determinants of the size of the health workforce and overall health expenditures
across fifteen OECD countries. Specifically, using the latest release of OECD
data, the analysis estimated and evaluated the effects of variables such as the
proportion of female physicians and the elderly, expenditures on ambulatory care,
enrollment levels in training programs, level of public financing, and per capita
income on the size of the health workforce and level of health spending between
1970-1991. The findings of this study help to place the problem of the changing
health workforce within the context of the complexity of health systems. It
confirms any understanding of what accounts for changes in the size of the health
labor force and expenditures require disentangling the effects of variables which
needs to be taken into account when considering health system reforms.
PMID- 11010125
TI - Political ideologies and health-oriented beliefs and behaviors: an empirical
examination of strategic issues.
AB - The area of health care has been called the most important political issue of the
1990s. Attitudes toward health care reform, increasing health costs, and
defensive medical practices have been examined in the public press and by
academicians. In addition, a substantial amount of research has been directed
toward the improvement of individual personal health due to changes in personal
health-related habits and behaviors. To date, there are relatively few studies
which have attempted to examine the political tendencies of a nationwide sample
of respondents as they relate to personal health-related beliefs and behaviors.
This article explores the consumer's views on critical questions relating to
health orientations and political tendencies. The results indicate a divergence
between the political orientations of respondents and their beliefs and behaviors
associated with health and wellness. Implications for policy-makers are
discussed.
PMID- 11010126
TI - The ABCs for deciding on a decision support system in the health care industry.
AB - As the information superhighway becomes clustered with various organizations
sharing the hope of staying solvent with the aid of technology, managers in the
health care industry are more and more looking to efficient Decision Support
Systems (DSS). The focus of DSS selection has often been on evaluations that
measure decision performance for determining the influence and efficacy of the
tool. Such evaluations, in many instances, ignore pertinent measurements for a
successful selection and implementation of a DSS. In this article, the authors
present a simple but important set of evaluation factors that can "make or break"
a DSS implementation in the health care industry.
PMID- 11010127
TI - First among (UN) equals: assessing hospital performance using data envelopment
analysis.
AB - This article explores the use of Data Envelopment Analysis (DEA) as a comparative
analytic tool to assess the relative effectiveness of competing hospitals.
Building on previous research with DEA in hospital efficiency analysis, the
authors extend the earlier technical efficiency-based DEA models to include
qualitative outcome measures. Data from hospitals in a regional competitive
health care market in South Florida are assessed using this new DEA model.
PMID- 11010128
TI - Performance appraisal: a primer for the lower level health care and
rehabilitation worker.
AB - This article reviews the use of performance appraisal in health care and
rehabilitation organizations, particularly as such an evaluation measure could be
used to examine the results achieved by managerial and supervisory level
personnel. This entails a reversal of the prevailing view, that is, appraisal of
lower level workers by "superiors" to a counter view as seen from those at "lower
levels" looking upwards. Hierarchies, of course, are facing increasing
challenges. Performance appraisal can serve the needs of the people at the lower
end as well as those defined as the "management." Ultimately, performance
appraisal can assure that all people in an organization will achieve benefits,
not just those at the managerial level.
PMID- 11010130
TI - 'Diagnostic tool' helps at-risk groups to analyze performance.
PMID- 11010129
TI - Open models encourage higher satisfaction rates.
PMID- 11010131
TI - Health plans still operating in the red at year-end 1998.
PMID- 11010132
TI - New report offers benchmarks for routine pediatrics care.
PMID- 11010133
TI - Capitation is alive and well in California, data suggest.
PMID- 11010134
TI - Benefit trends work against providers managing drug risk.
PMID- 11010135
TI - Assuring & improving the quality of in-home services.
AB - Long-term care represents the interface between health care and social services
and thus includes a multitude of services and staff that deliver long-term
assistance. The range of services, consumers, and environmental circumstances
under the home care umbrella creates a considerable challenge for both providers
and regulators. This article examines five principles to assure high-quality
care: Know your customers, listen to your customers, collect good information for
decision-making, understand that the group is smarter than the individual, and
realize that sub-optimization is a critical challenge facing organizations.
PMID- 11010136
TI - Predictions--long-term care in the next decade. Panel discussion.
PMID- 11010137
TI - Supporting aging in place & assisted living through home care.
AB - This article defines assisted living, discusses the pros and cons of limited
regulation, scope of service, Aging-in-Place partnerships, and how home care
agencies can work with assisted-living facilities to provide care. It also
examines a study on assisted living in six states that is funded by the Robert
Wood Johnson Foundation.
PMID- 11010138
TI - Family caregivers and home care: a declaration of interdependence.
AB - Family caregivers and home care providers need each other. They must recognize
their interdependence and learn to work together because millions of frail older
people, disabled adults, and medically fragile children rely on family members
and home care providers to help them live high-quality lives to the extent
possible.
PMID- 11010139
TI - Measurement: the key to success for providers, payors, and patients in long-term
care.
AB - The complex financing structure that supports home and community-based long-term
care services has resulted in the application of different quality assurance
requirements to similar services. Goals for home and community-based care are
viewed differently by providers, payors, and customers. This raises the issue of
how goals can be harmonized and what should be used to measure goals. Current
quality assurance strategies are judge insufficient to assure the delivery of
high-quality services; in part due to the state of health programs and lack of
unified outcome measurement. The need for multidimensional assessment to adopt a
baseline measure of health status to support allocation of services and enhance
successful client outcomes has become the aim for health care providers.
PMID- 11010140
TI - The new hospice compliance plan: defining and addressing risk areas. Part 2.
AB - The Department of Health and Human Services' (HHS) Office of the Inspector
General (OIG), has advised hospices and other health care providers to formulate
effective controls to ensure compliance with federal and state statutes, rules,
and regulations, and private-payor health care program requirements. This is the
second of three installments that focus specifically on the 28 risk areas
identified in the guidance and offer strategies for incorporating them in a
hospice compliance program. This article covers the areas of Expensive Care,
Documentation, Interdisciplinary Group, and Kickbacks.
PMID- 11010141
TI - Critical success factors for thriving under PPS.
AB - Home care agencies must work hard in the months ahead to successfully implement
PPS. The new system is a fair and equitable one. Home care agencies will have to
co-manage cost and quality. PPS, if implemented and administered appropriately,
will benefit both the provider and the patient. Proper planning and hard work
throughout the transition process will drive success. The prospective system is a
reality and will become effective October 1, 2000. Agencies must start now to not
only accomplish and meet the basic compliance issues, but also to develop the
change in processes needed to become efficient and cost effective.
PMID- 11010143
TI - Ensuring access to long-term care.
PMID- 11010142
TI - Canadian study shows promising results on home care cost effectiveness.
AB - Researcher Marcus Hollander, PhD, a former director of continuing care in British
Columbia, is leading a national effort to compare costs of providing treatment at
home to alternative settings including hospitals and nursing homes. The first
study compared costs incurred by home care clients to costs incurred by similar
persons in skilled nursing facilities and found home care costs were
significantly less for home care. The average savings ranged from 25% to 60%. The
first of 15 planned research projects on the cost effectiveness of home care to
be released during 2000 offers evidence of significant savings associated with
providing services in the home as compared to long-term institutions.
PMID- 11010144
TI - Home care equinox.
PMID- 11010145
TI - Building home care into managed long-term care: the VNS CHOICE model.
AB - New approaches to home and community-centered long term care offer strategic
opportunities for home health providers to thrive by providing expanded service
options for the growing population of chronically ill, frail elders. The
traditional expertise of home health providers makes a powerful combination with
the flexibility of capitation financing to successfully meet both the needs of
dually eligible older adults and government mandates to reduce overall
expenditures. VNS CHOICE, a home-centered, managed long-term care program, is
built on the principles and delivery system of home health care. By understanding
the VNS CHOICE service delivery model and lessons learned from its first two
years of operating experience, home care providers across the country may
identify innovations to incorporate into their agency product lines.
PMID- 11010146
TI - Want capital? Try a new approach.
PMID- 11010147
TI - The hospital blue chips.
PMID- 11010148
TI - Can we talk? Investors call for hospital financial feedback.
PMID- 11010149
TI - Riskier business. What health care organizations must do to restore investor
confidence.
PMID- 11010150
TI - Making choices. Crime and punishment.
PMID- 11010151
TI - The bionic century. More and more, doctors will be replacing worn-out organs with
donor or manufactured body parts.
PMID- 11010152
TI - Proteomics: the next frontier.
PMID- 11010153
TI - The uncomfortable & the unanswerable. New technologies raise an unending list of
ethical questions.
PMID- 11010154
TI - The ethics of e-commerce.
PMID- 11010155
TI - It doesn't come easy. A survey of hospital CEOs gives insight into collaboration.
PMID- 11010156
TI - Bridging the gap. By following new rules for working with physicians, health
systems can create a better health care product.
PMID- 11010157
TI - Lessons in scenario planning.
PMID- 11010158
TI - Health care's dark days.
PMID- 11010159
TI - Confronting the R&D imperative.
PMID- 11010160
TI - Web wager. Interview by D.O. Weber.
PMID- 11010161
TI - Lead user: a conversation with William Coyne.
PMID- 11010162
TI - We participate, therefore we are. Interview by Joe Flower and Patrice Guillaume.
PMID- 11010163
TI - Integrating health care in 3D.
PMID- 11010164
TI - An academic medical center reaches out.
PMID- 11010165
TI - Most wired innovator awards.
PMID- 11010166
TI - Destabilization: it's everywhere and all at once.
PMID- 11010167
TI - Building organizational fitness.
PMID- 11010168
TI - The new market makers.
PMID- 11010169
TI - Making choices. Service with a snarl.
PMID- 11010170
TI - Complying with outpatient PPS implementation.
PMID- 11010171
TI - Turnaround, sell or shut-down: how executives can decide the future of hospital
systems' business and assets.
PMID- 11010172
TI - Capitation now moving to less competitive markets, long-term contracts,
consultant says.
PMID- 11010173
TI - MedQuist prospers as hospitals step up outsourcing of medical record
transcription.
PMID- 11010174
TI - Nurse shortage worse than you think, but sensitivity may help retain nurses.
PMID- 11010175
TI - You can win a price war started by a competitor.
PMID- 11010177
TI - The value of sponsorship.
PMID- 11010176
TI - Imagine the possibilities.
PMID- 11010178
TI - Never underguesstimate the financial future of Medicare.
PMID- 11010179
TI - Balancing a large scale of responsibility: an interview with R. Milton Johnson.
PMID- 11010180
TI - Off-balance-sheet financing can generate capital for strategic development.
AB - To manage their real estate portfolios effectively and obtain funding for
strategic development, IDSs should consider adopting off-balance-sheet financing
strategies, such as sale-and-leaseback transactions, synthetic leases, and joint
venture arrangements. Under these approaches, real estate assets are moved off of
the organization's balance sheet via a partial or complete transfer of ownership
to a third-party entity. The organization typically retains a satisfactory degree
of control over the assets as lessee in sale-and-leaseback and synthetic-lease
arrangements, or limited or minority partner in a joint venture, while freeing up
cash to use for other strategic purposes.
PMID- 11010181
TI - A new risk management paradigm for managed care.
AB - The long-term outlook for managed care may be threatened by current capitation
rate-development methods that adjust risk for age, gender, geographic area,
income level, and occupation, but not health status. Not only provider payments,
but also patient access may be compromised as a result. New risk-adjustment
methods that categorize patients into groups based on their current health status
and anticipated disease progression allow fairer distribution of the essential
components of costs to deliver healthcare services to the at-risk population, and
improve upon HCFA's adjusted average per capita cost (AAPCC) rates and recently
implemented principal inpatient diagnostic cost group (PIP-DCG) risk-adjustment
methodology.
PMID- 11010182
TI - Cape: imagining the possibilities for health care and HFMA.
PMID- 11010183
TI - Achieving a balance between risk and return.
AB - Because risk management is costly, many health plans and providers practice risk
avoidance by transferring risk to other entities. Risk-bearing healthcare
organizations can improve their return on assets, but to do so they need complete
information about patients' health status and the availability of effective
medical treatment. To improve their return on assets, providers can use risk
management strategies such as growth, designing incentives to encourage providers
and health plans to reduce or eliminate unnecessary variations in resource use,
and improving information about the reasons for variations in resource use and
controlling those variations when possible. Providers need data to analyze why
variations in resource use occur and to evaluate the efficiency of their resource
use.
PMID- 11010184
TI - Controlled-risk foreign investment strategy can boost yields.
AB - Healthcare organizations that have invested in the U.S. stock market have enjoyed
high returns in recent years. After such a performance, many investment managers
see little reason to investigate overseas markets, believing that the U.S. market
will continue to be profitable and economic uncertainties make overseas markets
too risky. However, in 1999, markets in Europe, Australia, and the Far East
outperformed the S&P 500 for the first time in five years. In addition, signs
such as mounting price/earnings ratios may indicate that the U.S. stock market
will be less profitable than it has been in recent years. Consequently,
investment managers should revisit the idea of international investing.
PMID- 11010185
TI - HCFA tightens eligibility requirements for provider-based status.
AB - On October 10, 2000, HCFA will implement new eligibility standards for all off
campus entities with a provider-based designation. Providers that wish to retain
the provider-based status of their ambulatory care facilities need to take action
to more fully integrate the ambulatory care facilities with their main
facilities. In addition, the provider will need to show that 75 percent of the
patient population served by the ambulatory care facility also is served by the
provider's main facility.
PMID- 11010186
TI - OIG offers guidance on the legality of telemedicine arrangements.
AB - Telemedicine increasingly is being used to enable patients in rural areas to gain
access to specialists. At the same time, concerns have arisen about the legality
of certain telemedicine applications. To date, the HHS Office of Inspector
General (OIG) has issued two advisory opinions stating it would not impose
sanctions on two specific telemedicine arrangements, where potential violations
of the antikickback statute could exist. These opinions, while applying only to
the specific arrangements in question, provide physicians with clues to the OIG's
thinking on various arrangements they may wish to initiate.
PMID- 11010187
TI - Transitional corridors delay outpatient payment reductions.
PMID- 11010188
TI - Application service providers: virtual information managers.
PMID- 11010189
TI - Credentials and their impact on career advancement.
PMID- 11010190
TI - Data trends. Hospital financial squeeze tightening.
PMID- 11010191
TI - The high-touch financial manager.
PMID- 11010192
TI - Patient-friendly billing.
PMID- 11010193
TI - Should Medicare remain an entitlement?
PMID- 11010194
TI - The five-word CFO job description: an interview with Lowell W. Johnson.
PMID- 11010195
TI - Restructuring patient financial services for maximum effectiveness.
AB - Following its formation as a regional IDS, John Muir/Mt. Diablo Health System in
Walnut Creek, California, adopted an innovative approach to reorganizing its
patient financial services (PFS) functions. Instead of consolidating all PFS
functions into a single centralized business office, the IDS divided PFS
leadership responsibilities into two areas: daily operations and technical
functions. The director of daily operations oversees PFS clerical staff who are
responsible for admitting functions, billing, follow-up, and related activities.
The director of technical functions is responsible for implementing, uploading,
and maintaining the various information systems; contract tracking and
compliance; and regulatory compliance.
PMID- 11010196
TI - An integral approach to compliance.
AB - Financial managers of managed care organizations should structure their
compliance plans to conform with requirements shaped by forces such as judicial
decisions and extralegal standards for managed care operations, in addition to
state and Federal laws and regulations. In addition to researching the law and
training employees, an integral compliance plan should include monitoring
organizational systems that can encourage or impede compliance, measuring
employees' motivation to adhere to compliance standards, and modifying corporate
culture to support compliance goals. Managed care organizations should empower
compliance officers with a broad range of tools to assess and improve compliance
efforts, or risk having organizational decisions examined externally through the
lens of an onerous, dynamic system of laws and judicial decisions.
PMID- 11010197
TI - Achieving superior productivity.
AB - Hospitals need to analyze, develop, and implement realistic, effective
productivity standards. The first step in a productivity analysis is to collect
performance data for each hospital department. A workload measure should be
assigned to every department. Comparing historical performance data for each
department highlights problem areas. Gaining executive commitment and department
manager acceptance is essential to productivity-improvement initiatives. Even in
departments that experience a change in function, historical data can be used to
monitor performance and determine where improvement is needed. A weighting system
can be employed to capture historical data and establish a standard against which
to measure future performance.
PMID- 11010198
TI - Your organization should consider a cash-balance pension plan.
AB - In recent years, a growing number of healthcare organizations have dropped the
traditional defined-benefit pension plan and adopted cash-balance pension plans.
A cash-balance pension plan generally allows employers to pay less in overall
pension benefits and administration costs. A cash-balance pension plan pays
benefits according to a predetermined formula based on an average of the
employee's annual salary over his or her length of service. This provides
recognizable benefits to younger employees but lower overall benefits to
employees who have a long length of service. To assuage employees who may feel
cheated out of the pension benefits they expected, employers that change to a
cash-balance pension plan should consider offering higher guaranteed growth
rates, advanced notification of the change to the new plan, and generous early
retirement options for employees with longer lengths of service.
PMID- 11010200
TI - Soft landings: dissolving a physician network.
AB - Many healthcare organizations established physician networks to strengthen their
competitive position in the marketplace. Many of these networks, however, have
been unprofitable. As a result, some healthcare organizations are dissolving
their networks. Healthcare organizations should plan the dissolution carefully
and help the physicians establish an infrastructure for their new practices. By
easing the physicians' transition to independent practice, healthcare
organizations ensure the likelihood of a continued business relationship with the
physicians in the future.
PMID- 11010199
TI - The changing role of internal auditors in health care.
AB - Two surveys of directors of internal auditing in health care conducted in 1990
and 1998 found that healthcare internal auditors are spending proportionately
more time on management and operational improvement activities and less time on
traditional financial/compliance activities. The average staff size has remained
relatively constant, but salaries at all levels of experience have risen. More
importantly, the tenure of healthcare internal auditors has increased
significantly since 1990. The profile of the healthcare internal auditing
director also has changed. The director is older, more experienced, and has held
the position for twice as long as was the case in 1990. On the other hand, the
director is more stressed and less satisfied with compensation.
PMID- 11010201
TI - OIG clarifies emergency care requirements for providers and plans.
PMID- 11010202
TI - Evaluating ASP pricing models and contract terms.
PMID- 11010203
TI - Supporting organizations give donors more control.
PMID- 11010204
TI - The smart approach to buying cash management services.
PMID- 11010205
TI - Integrity is integral to career success.
PMID- 11010206
TI - Data trends. Hospital financial indicators show little improvement.
PMID- 11010207
TI - How consumers evaluate health care quality: Part III.
AB - This article is the third and final article in a series which examines the way in
which consumers assess information regarding the quality of health care services.
The previous article focused on consumers' perceptions of health care plans and
health insurance companies. This article examines the views of health care
consumers regarding hospitals and doctors.
PMID- 11010208
TI - Effects of direct-to-consumer advertising of pharmaceutical products on college
students.
AB - This study examines college and university students' responses to direct-to
consumer advertising of pharmaceutical products in magazines. Four hundred
seventy-one students from three institutions participated in the study that found
that the majority of the students were frequent magazine readers, they noticed
ads for the pharmaceutical products, and they used the advertised products.
Although most students denied buying or using the products because of the ads,
there was a significant correlation between number of ads seen and number of
products used.
PMID- 11010209
TI - Client satisfaction with substance abuse treatment.
AB - A survey of 15 publicly-funded treatment agencies in Iowa was conducted to
identify correlates of satisfaction with substance abuse treatment for voluntary
clients. We used stratified least-squares regression analysis to identify program
characteristics that were associated with greater satisfaction levels. In order
to investigate satisfaction among voluntary clients, we stratified the data using
three measures of client choice. These were self-reports of the extent to which
the respondent felt pressured by the threat of jail, legal action, or family
demands. Women tended to be more satisfied than men. Satisfaction scores for
clients who indicated they were in treatment by choice were correlated with
judgements about program characteristics. Phone availability, time with
counselor, counselor skill, and sensitivity were associated with greater levels
of satisfaction in all three models. Parking, privacy and cleanliness were
significant in two out of three models.
PMID- 11010210
TI - The marketing function in managed care systems.
AB - As managed care spreads through the health care service industry, marketing
professionals are faced with the challenge of marketing highly integrated
systems. This paper explores three questions related to this development: (1)
what is unique about managed care marketing, (2) how has managed care impacted
health care marketing, and (3) what new strategies and trends will shape these
developing markets?
PMID- 11010211
TI - Low recall of local television health care news segment topics, sponsors and
program names.
AB - In an effort to examine the effectiveness of hospitals' sponsoring of local
broadcast news health care segments, viewer recall of information presented in
news reports, the program name of the reports, and the names of the hospital
sponsors of those reports were analyzed. Despite the fact that telephone survey
respondents said they place a higher value on televised health care information
than they do for other mass media, recall was found to be generally poor. A
majority of respondents could not name the topic of the televised health news
report they had viewed, the program name or the program sponsor.
PMID- 11010212
TI - Marketing syringe/needle exchange programs.
AB - In an effort to bring the AIDS epidemic under control among the highest risk
population of injecting drug users, Syringe/Needle Exchange Programs are being
considered, developed and implemented. This paper looks at some of the programs
in the United States in various stages of development. Also discussed will be the
medical, social and political issues surrounding Needle Exchange Programs.
PMID- 11010213
TI - Accuracy of information on printed over-the-counter drug advertisements.
AB - Direct-to-consumer drug advertising is a useful medium for educating people and
disseminating product information. Consumers make product purchase decisions
based on the information gained from advertisements. If advertisements are
misleading, consumers may not have adequate drug knowledge to detect this
misinformation. The objective of this study was to evaluate print advertisements
for over-the-counter (OTC) products. Five clinical pharmacists evaluated print
advertisements appearing in three consumer periodicals. Advertisements were
selected over a nine month period beginning January 1994. Accuracy of information
on OTC advertisements was determined based on federal guidelines. Additionally,
reviewers identified deficiencies in advertisements that may mislead consumers.
According to reviewers, around 50% of advertisements lacked accurate statements.
Side effects were indicated on only one advertisement. All advertisements were
indicated by reviewers to be more promotional than educational. Reviewers
indicated that more than 50% of advertisements lacked information essential for
consumers to make an informed choice during self-medication decisions. This study
indicates that OTC drug advertisements lack information necessary for consumers
to make informed purchase decisions. Inaccurate information and lack of
information on side effects could mislead consumers causing harmful adverse
events.
PMID- 11010214
TI - Customer satisfaction and consumer responsibility: toward an alternative model of
medical service quality.
AB - In the increasingly competitive environment of medical services and patient care,
physicians feel a strong pressure for increasing efforts to improve patient
satisfaction with the goal of creating a loyal patient base. These steps to
promote patient satisfaction have typically involved developing new programs and
services, as medical offices seek to attract and keep their patients by
continually enhancing service features. While patient satisfaction is a worthy
goal, this paper argues that we often make mistakes and incur expensive costs in
pursuing satisfaction as an end unto itself. This paper proposes an alternative
model, based on creating a doctor-patient therapeutic alliance which has the dual
benefits of enhancing patient satisfaction while improving the critical personal
relationship between doctors and their patients, so necessary for the delivery of
optimal care.
PMID- 11010215
TI - Primary health care in the reforms of the health care system: an analysis of
reformation schemes of emerging and developing countries as applied to the
Republic of Macedonia.
PMID- 11010216
TI - Access as a managed care marketing outcomes measure.
AB - As their position in the health care market diminishes, HMOs are feeling the
pinch from the competition. Purchasers of health plans have many more options
available today than in the past. Employers can select from single or
consolidated health plans, plans offered by coalitions, or plans offered by
provider systems. Following closely behind the withstanding issue of controlling
costs is quality of care and customer satisfaction. The bad press surrounding
managed care is making employers demand assurances that employees will receive
the best quality of care their money can buy. To assist in this endeavor managed
care companies are focusing more on their customers. To this end marketers use
report cards to assess purchaser and enrollee satisfactions, with the hope that
if they have a happy customer, s/he will be a loyal one. This paper reviews
current marketing strategies of managed care companies and their level of
usefulness with respect to sustaining customers and hence market share.
PMID- 11010217
TI - Perceptions of care and satisfaction in assisted living facilities.
AB - This study had two objectives: (1) to determine current consumers' perceptions
and satisfaction with assisted-living facilities and (2) to determine current
consumers' evaluation and preferences for nursing assistants. Responses from
residents and family members indicated positive, but not strong, satisfaction
with care. Areas identified as often unsatisfactory were; the mealtime
experience, the nursing assistants, and recreational activities. Preferred
qualities of nursing assistants identified by both residents and family members
were genuine concern, kindness, respect, and consistent attentiveness. Residents
only identified a pleasant disposition as an essential quality of nursing
assistants and only family members identified knowledge regarding aging, gentle
assertiveness, and commitment to staying on the job as essential qualities of
nursing assistants.
PMID- 11010218
TI - An analysis of the demand for regular dental health care: implications for
marketing.
AB - The more information a dentist has concerning factors that affect the demand or
lack of demand for dental care the greater his or her capability to profile
client markets. Logically the more exact the profiling of clients (potential
clients) the better able the dentist is to develop a marketing program that is
responsive to various market segments. In this paper the authors report findings
extracted from an extensive health assessment survey which shed light on factors
influencing the demand for dental services. Responses from 1934 residents of a
large southeastern metropolitan area were analyzed. Statistical analyses of the
data were conducted to determine whether or not a relationship existed between
dental care utilization and the presence/absence of dental insurance, gender,
racial/ethnic background, and household income. The potential implications these
factors may have on marketing a dental practice are explored and recommendations
presented.
PMID- 11010219
TI - Benefit and risk information in prescription drug advertising: review of
empirical studies and marketing implications.
AB - As pharmaceutical companies began to advertise prescription drugs directly to
consumers as well as to physicians, understanding the impact of benefit and risk
information in drug advertising on physicians and consumers has become more
critical. This paper reviews previous empirical studies that examined the content
of benefit and risk information in drug advertising and its potential effects on
physicians' subsequent prescribing behaviors. It also reviews studies that
investigated how consumers process information on a drug's efficacy and side
effects. Based on the findings of these studies, implications are discussed for
effective marketing information development as well as for government regulation.
PMID- 11010220
TI - Regulatory effects in health care: philosophies, impacts, and free markets.
AB - In spite of the fact that other service sectors such as airlines, retail banking,
telecommunications, railroads, trucking, securities brokerage, and insurance have
experienced remarkable transformations toward more deregulated environments, the
health care industry continues to be very heavily regulated. This article first
examines the major theories and general schools of thought surrounding the
concept of regulation in general, followed by an examination of the influence
governmental regulations have had on hospitals in particular, specifically as
they relate to stimulating competitiveness, efficiencies, and cost control.
PMID- 11010221
TI - An open system approach to process reengineering in a healthcare operational
environment.
AB - The objective of this study is to examine the applicability of process
reengineering in a healthcare operational environment. The intake process of a
mental healthcare service delivery system is analyzed systematically to identify
process-related problems. A methodology which utilizes an open system orientation
coupled with process reengineering is utilized to overcome operational and
patient related problems associated with the pre-reengineered intake process. The
systematic redesign of the intake process resulted in performance improvements in
terms of cost, quality, service and timing.
PMID- 11010222
TI - Direct and indirect costs of schizophrenia in community psychiatric services in
Italy. The GISIES study. Interdisciplinary Study Group on the Economic Impact of
Schizophrenia.
AB - BACKGROUND: The present work is a cost-of-illness (COI) study that aims at
assessing total direct and indirect costs of schizophrenic patients in community
psychiatric services in Italy and identifying the variables that influence costs.
METHODS: A retrospective prevalence-based multi-centre COI study, was designed.
Ten community mental health centres (CMHC) were involved and 100 patients were
recruited. Data on patients' costs were gathered through specifically designed
instruments. RESULTS: More than half total direct costs were attributed to CMHC
interventions. The yearly average costs of schizophrenia per patient amounted to
nearly ITL 50 million: 30% for direct costs and 70% for indirect costs.
CONCLUSION: CMHCs tend to manage long-term ill patients by adopting a strong
community-based system of care. Schizophrenia is correlated to loss of working
days and lack of well-being. From the results of this study, it might be argued
that the de-institutionalisation programme has produced 'spillovers' in terms of
families' greater involvement in patients management.
PMID- 11010223
TI - A qualitative study of the extent to which health gain matters when choosing
between groups of patients.
AB - There is considerable debate about the appropriateness of allocating health care
resources on the basis of the size of the health improvement that they generate.
The aim of this study was to elicit the general public's views about the extent
to which health gain matters vis-a-vis other considerations. A total of 60
respondents took part in group discussions designed to enable them to raise,
discuss, and reflect upon, different arguments. The qualitative data showed that
many responses were being generated by factors that were not directly included in
the questions, and so it is difficult to meaningfully interpret the results of
other studies which have asked similar questions but which have not looked at the
reasons underlying the responses. However, a clear message did come through from
the data; namely, that equality of access should prevail over the maximization of
benefits. However, this was subject to the outcome constraint that treatments are
sufficiently effective. An important question for future research, then is 'how
effective do treatments have to be for the principle of equal access to apply?'
PMID- 11010224
TI - Medicare's DRG-weights in a European environment: the Spanish experience.
AB - Hospital payment systems are being changed to mixed systems, composed of case-mix
categories and structure indicators. The Health Care Financing Administration's
Diagnosis-Related-Groups (HCFA's DRG-weights are used in Catalonia as Prospective
Payment System (PPS)-instruments for hospital inpatient reimbursement. The
Catalonian and Spanish health systems, however, are very different from the US
health environment. The aim of this study is to determine whether the HCFA's DRG
weights fit the special characteristics of a European environment. To do this,
cost-based weights, determined from information from the cost accounting system
of two public hospitals in Barcelona, are compared with Medicare-weights. A total
of 35 262 discharges representing 12 794 million pesetas are analyzed. Medicare
weights do not differ globally from cost-based-weights and the adjusted
correlation weighted least squares regression between the two weight-scales is
95%. There are, however, systematic deviations in six DRG-groupings. The most
important deviations are concentrated in Ambulatory Surgery categories, in DRGs
in which prostheses are used, and in specialties excluded from several PPSs
because of extreme variables in treatment intensity. In conclusion, Medicare
weights can be used to pay hospital output in European environment but they
should be adjusted to avoid systematic deviations.
PMID- 11010225
TI - Leadership and the UK health service.
AB - This paper explores future leadership requirements for health services in the
context of relevant leadership theory and the changing environment for health
services in the UK. The output of leadership research is both prolific and
confusing and its applicability to health services management uncertain
especially in the context of constraints on the strategic managerial behaviour
and choices of public service managers. The introduction of general management to
the UK NHS in the 1980s, followed by an internal market for health care in 1990
should have provided the opportunity for managers to work differently and to
create personal space for leadership. However, it is not known whether
sustainable , new ways of leadership working have emerged although it is
reasonable to hypothesis from studies elsewhere that a number of contextual and
behavioural leadership models are likely to be found in the NHS. Although
management researchers have explored networking and referred to the impact of the
external environment of leadership, insufficient importance has been attached to
date to the impact of future trends in health services on the leadership of
change in the health sector. The paper argues that in future health services
leadership will require much more than traditional networking with other
organizations and groups and will need to focus on developing and securing
external agreement to an agenda for positive change turning the apparent
constraints of the external environment, determined primarily by government
policies,into opportunities. In other words, the demands of external or
contextual leadership will increase forcing a stronger focus on having to achieve
change through others.
PMID- 11010226
TI - Five giant leaps toward integrating health care delivery and ways to drive
organizations to leap or get out of the way.
AB - The article argues that incremental improvement of, or "tinkering" with, health
care delivery is taking too long and leaves unacceptable gaps in health care
quality and service. It lists five common types of quality improvement "leaps"
that have proven across studies to improve the integration of care during
hospital and emergency department discharge, to bring mental health and substance
abuse treatment into primary care, and to allow better management of chronic
diseases. It also lists five key tasks that organizations need to accomplish in
order to make such leaps and then describes four ways that consumers, employers,
consumer advocates, and investors force the stubborn "bullfrogs" to take a big
jump forward.
PMID- 11010227
TI - Changing the paradigm: planning for ambulatory care expansion in Los Angeles
County using a community-based and evidence-based model.
AB - In 1998, Los Angeles County's Department of Health Services (DHS) embarked on a
planning process to expand ambulatory care services for the county's 2.7 million
uninsured and otherwise medically indigent residents. This planning process was
novel in two ways. First, it used a quantitative, needs-based approach for
resource allocation to ensure an equitable distribution of safety-net ambulatory
care services across the county. Second, it used a new community-based planning
paradigm that took into consideration the specific needs of each of the county's
eight geographic service planning areas. Together, the evidence-based approach to
planning and the community-based decision-making will ensure that DHS can more
equitably provide for the needs of Los Angeles County's medically indigent
residents.
PMID- 11010228
TI - Reassessing the plight of physician organizations in California: the uncertain
future for IPAs.
AB - With numerous medical groups and individual practice associations (IPAs) in
California now reporting operating losses--and many approaching financial
insolvency--the question arises why physician organizations are in such a tenuous
situation. One line of thinking is that the problem is attributable to the market
dominance of the major health plans and their ability to impose actuarially
unsound low capitation rates on professional providers. This article describes
four other reasons for the current plight of physician organizations: (1) a
physician-centric approach to IPA governance, (2) lack of qualified staff within
key operating units, (3) management reporting that is insufficient to support
utilization analysis and health plan negotiations, and (4) a highly charged
political process for determining physician reimbursement. IPA survival will
ultimately depend upon whether IPAs are perceived by their physician members and
leaders as true business operations or just as another income source.
PMID- 11010229
TI - Kaiser Permanente: integrating around a care delivery model.
AB - The risk-adjusted payment model mandated for Medicare + Choice organizations by
the Balanced Budget Act of 1997 has significant implications for health care
organizations that offer the Medicare + Choice program. Chronic medical
conditions in the ambulatory care setting will become the focus of data capture,
requiring significant retooling of ambulatory care operations. Health care
organizations in California currently do not have the capital available to invest
in the information management tools that will be required. Private practitioners
continue not to have the technology and expertise to capture the data needed to
run the model. Nevertheless, the risk-adjusted payment model presents the
potential to better integrate care delivery around the continuum of health care
needs of the population.
PMID- 11010230
TI - The rise and fall of a hospital-sponsored group practice.
AB - Each physician group, network, or management services organization developed as
part of an "integration" strategy over the past decade is unique. The current
status of each of these entities is based on a variety of factors, including the
local health care economy and environment, the sponsoring organization, and the
entity's leadership. Much of the current news concerning integration initiatives
is negative, and significant operating losses and the disillusionment of the
participants have been reported. It is important to study the failures, however,
for despite the unique factors impacting each one there are universal lessons to
be learned in every case. This article chronicles the causes of one integrated
group practice's breakup after five years of operation and the process undertaken
to return the physicians to small independent practices.
PMID- 11010231
TI - The integration movement in California's workers' compensation market.
AB - Over the past two decades the California workers' compensation industry has been
responding to rapidly rising medical costs. The first response was to attempt to
adopt principles of managed care; the second, to increase efficiency by
integrating activities, first within companies, then between companies and
providers, and finally across companies providing both group health and workers'
compensation. This article chronicles the integration movement, analyzes the
forces driving it, and discusses how contradictory government incentives have
both propelled and hindered integration.
PMID- 11010233
TI - Addiction as a market failure: using rational addiction results to justify
tobacco regulation.
AB - Tobacco regulation efforts have been criticized by some academic economists for
failing to provide adequate welfare-analytic justification. This paper attempts
to address these criticisms. Unlike previous research that has discussed second
hand smoke and health care financing externalities, this paper develops the logic
for identifying the much larger market failures attributable to the failure of
smokers to fully internalize the costs of their addictive behavior. The focus is
on teen addiction as a form of "intrapersonal" externality and observed adult
consumption behavior consistent with partial myopia. The importance of peer
effects, in the consideration of welfare impacts, is also emphasized.
PMID- 11010232
TI - The National Health Service Corps for the 21st century.
AB - The National Health Service Corps (NHSC) was created in 1970 to provide primary
health care clinicians for the underserved. The article includes a review of the
peer-reviewed and intragovernmental literature on the NHSC program from 1971 to
1998 and also presents a current profile of the program. Despite significant
increases in NHSC field strength since 1991, the 2,439 clinicians meet only 12%
of the need for primary health care providers in underserved areas. While the
NHSC has successfully addressed clinician diversity and retention issues,
community and site development remain barriers to increasing access. Most
communities in need are not ready to recruit and support clinicians. The NHSC of
the next millennium must work with the neediest communities to reach the
appropriate stage of readiness. Only after completing the necessary
"preplacement" activities can the NHSC assist in the recruitment and placement of
clinicians to increase access.
PMID- 11010234
TI - On the economic foundations of CEA. Ladies and gentlemen, take your positions!
AB - There are still many ongoing debates about several aspects of the methodology of
economic evaluations of health care interventions. Some of the disparities in
recommendations on methodological issues may be traced back to different
viewpoints on cost-effectiveness analysis (CEA) in general. Two important views
are the welfarist approach, which aims at embedding CEA into traditional welfare
economics, and the decision maker's approach, which takes a broader and more
pragmatic view on CEA. The focus in welfarism may be on utility while that of the
decision maker's approach may be considered to be on health. In this paper it is
examined how these two views differ and how these differences may subsequently
lead to debates in methodological areas. It is indicated that embedding the
practical operationalization of CEA in welfare economics seems impossible. In a
strict welfarist approach it is necessary to view QALYs as being utilities,
although one may question whether such an approach to QALYs is appropriate. Also,
equity considerations may play an important role in cost-effectiveness analysis
and these should preferably be taken into account in a way that reflects societal
attitudes towards an equitable distribution of health care. These equity
considerations may not always be directly related to utility or efficiency.
Furthermore, both camps may prefer different methods for cost measurement in
areas such as productivity costs and informal care. A better recognition of the
contents and origins of controversies and disputes may enhance the clarity of
discussions.
PMID- 11010235
TI - On stationarity and cointegration of international health expenditure and GDP.
AB - This paper examines stationarity and cointegration of health expenditure and GDP,
for a sample of 21 OECD countries using data for the period 1960-1997, by
applying a test battery that allows robust inference to be made on the
stationarity and cointegration issue. Trend stationarity and no-cointegration are
tested using new country-by-country and panel tests, not previously applied in
this setting. New results for country-by-country and panel tests of non
stationarity and cointegration are presented. Our unit root and trend
stationarity results indicate that both health expenditure and GDP are non
stationary. The no-cointegration and cointegration results indicate that health
expenditure and GDP are cointegrated.
PMID- 11010236
TI - Properties of actuarially fair and pay-as-you-go health insurance schemes for the
elderly. An OLG model approach.
AB - The aged dependency ratio or ADR is growing at a fast pace in many countries.
This fact causes stress to the economy and might create conflicts of interest
between young and old. In this paper the properties of different health insurance
systems for the elderly are analysed within an overlapping generations (OLG)
model. The properties of actuarial health insurance and different variations of
pay-as-you-go (PAYG) health insurance are compared. It turns out that the welfare
properties of these contracts are heavily dependent on the economy's dynamic
properties. Of particular importance is the magnitude of the rate of population
growth relative to the interest rate. In addition, it is shown that public health
insurance is associated with an inherent externality resulting in a second-best
solution.
PMID- 11010237
TI - Risk segmentation: goal or problem?
AB - This paper traces the evolution of economists' views about risk segmentation in
health insurance markets. Originally seen as a desirable goal, risk segmentation
has come to be viewed as leading to abnormal profits, wasted resources, and
inefficient limitations on coverage and services. We suggest that risk
segmentation may be efficient if one takes an ex post view (i.e., after
consumers' risks are known). From this perspective, managed care may be a much
better method for achieving risk segmentation than limitations on coverage. The
most serious objection to risk segmentation is the ex ante concern that it
undermines long-term insurance contracts that would protect consumers against
changes in lifetime risk.
PMID- 11010238
TI - An efficient employer strategy for dealing with adverse selection in multiple
plan offerings: an MSA example.
AB - This paper outlines a feasible employee premium contribution policy, which would
reduce the inefficiency associated with adverse selection when a limited coverage
insurance policy is offered alongside a more generous policy. The "efficient
premium contribution" is defined and is shown to lead to an efficient allocation
across plans of persons who differ by risk, but it may also redistribute against
higher risks. A simulation of the additional option of a catastrophic health plan
(CHP) accompanied by a medical savings account (MSA) is presented. The efficiency
gains from adding the MSA/catastrophic health insurance plan (CHP) option are
positive but small, and the adverse consequences for high risks under an
efficient employee premium are also small.
PMID- 11010239
TI - Health insurance and retirement behavior: evidence from the health and retirement
survey.
AB - This paper studies the role of health insurance in the retirement decisions of
older workers. As policymakers consider mechanisms for how to increase access to
affordable health insurance for the near elderly, considerations of the potential
labor force implications of such policies will be important to consider-
potentially inducing retirements just at a time when the labor force is
shrinking. Using data from the 1992 and 1996 waves of the Health and Retirement
Survey, this study demonstrates that access to post-retirement health insurance
has a large effect on retirement. Among older male workers, those with retiree
health benefit offers are 68% more likely to retire (and those with non
employment based insurance are 44% more likely to retire) than their counterparts
who would lose employment-based health insurance upon retirement. In addition,
the study demonstrated that in retirement models, when retiree health benefits
are controlled for, the effects of pension coverage are reduced, suggesting that
these effects may have been overestimated in the prior literature.
PMID- 11010240
TI - A note on eliciting distributive preferences for health.
AB - While in theory the strength of preferences for equity in health can be expressed
in an 'inequality aversion parameter', in practice, analysts would have to obtain
them from people's choices. We are faced with a number of methodological problems
when turning to this type of empirical research. This note investigates which
types of preference could explain the choices people make when responding to
equity-efficiency questions of this kind. Respondents may be heavily influenced
by concerns that are not related to their equity preferences, something which may
lead them to choose distributions that are not consistent with models on the
equity-efficiency trade-off. Specifically, a threshold effect is identified,
which could explain why some people would rather prefer to concentrate than to
diffuse health gains. The second aim of this note is to offer some lessons from a
survey which was designed for eliciting people's distributive preferences for
health gains.
PMID- 11010241
TI - How the dead help me care for the living.
PMID- 11010242
TI - Easy ways to track your progress.
PMID- 11010243
TI - I couldn't let the patient die--not yet.
PMID- 11010244
TI - My depression has made me a better doctor.
PMID- 11010245
TI - Is any malpractice settlement really confidential?
PMID- 11010246
TI - Is primary care paying its way?
PMID- 11010247
TI - "Internists are losers".
PMID- 11010248
TI - Should we stop making a fuss over HMOs?
PMID- 11010249
TI - The same old problems with FFS Medicare payments.
PMID- 11010250
TI - Discounted Medicare? It's already here.
PMID- 11010251
TI - Where were my dad's doctors?
PMID- 11010252
TI - Scapegoating won't reduce medical errors.
PMID- 11010253
TI - The patient came first--mom and dad would have to wait.
PMID- 11010254
TI - The fourth pearl of internship.
PMID- 11010256
TI - What a behavioral specialist could add to your practice.
PMID- 11010255
TI - A doctor's worst nightmare: my own child has cancer.
PMID- 11010257
TI - When I treated Grace, I also treated myself.
PMID- 11010259
TI - Managed care ripoffs. Don't sign a sucker deal.
PMID- 11010258
TI - Your liability when you teach residents.
PMID- 11010260
TI - Managed care ripoffs. Are you being paid less than you should?
PMID- 11010261
TI - Plain and simple: denying payment denies care.
PMID- 11010262
TI - Turn your computer into a patient education library.
PMID- 11010263
TI - Supreme Court: your office can be searched without a warrant.
PMID- 11010264
TI - Hang it up at 55? No way!
PMID- 11010266
TI - Do you need critical-illness insurance?
PMID- 11010265
TI - What are you really good at?
PMID- 11010267
TI - Are online pharmacies good for your patients--and for you?
PMID- 11010268
TI - Let's audit the HMOs!
PMID- 11010269
TI - From private tragedy to public activism.
PMID- 11010270
TI - Let's stop subsidizing lawyers at medical meetings.
PMID- 11010271
TI - What makes a physician an expert in CAM?
PMID- 11010272
TI - How high-tech private eyes catch malingering plaintiffs.
PMID- 11010273
TI - Patient fraud--or an invasion of privacy?
PMID- 11010274
TI - "Boutique" practices: good medicine--or ethical swamp?
PMID- 11010275
TI - Let's put an end to code "bungling".
PMID- 11010276
TI - Redefining hope.
PMID- 11010277
TI - Re-engineering your practice. Never lose a chart again!
PMID- 11010279
TI - The 150 best financial advisers for doctors.
PMID- 11010278
TI - How I learned to be a better boss.
PMID- 11010280
TI - Living--and practicing--with hepatitis C.
PMID- 11010281
TI - Our patient pulled a fast one on Medicare--and on us.
PMID- 11010282
TI - How do you unload an obsolete computer?
PMID- 11010283
TI - Compliance guidelines for small practices: no more excuses.
PMID- 11010284
TI - Oops! Doctors' worst financial blunders.
PMID- 11010285
TI - Doctors and the Web. Build your own information highway.
PMID- 11010286
TI - My second specialty? It's suing lawyers.
PMID- 11010287
TI - A lifelong ally for cystic fibrosis patients.
PMID- 11010288
TI - Acupuncture in 2000: working its way into mainstream medicine.
PMID- 11010289
TI - The job paid nothing, but the rewards were great.
PMID- 11010290
TI - If they treat a doctor this way, what must patients endure?
PMID- 11010291
TI - My malpractice case was a blessing in disguise.
PMID- 11010292
TI - Dr. Mom--an oxymoron?
PMID- 11010293
TI - Doctors who go the extra mile. Treating his far-flung patients like family.
PMID- 11010294
TI - If you're so smart, doctor, why aren't you rich?
PMID- 11010295
TI - Endoscopy at 35,000 feet: hand me that duct tape!
PMID- 11010296
TI - Malpractice consult. When the patient doesn't fit the mold.
PMID- 11010297
TI - Where's managed care headed?
PMID- 11010298
TI - Will health care decide who goes to the White House?
PMID- 11010299
TI - Staff raises. The purse strings won't be any looser this year.
PMID- 11010300
TI - How we'll survive our next computer switchover.
PMID- 11010301
TI - How to cut loose from a troublesome patient.
PMID- 11010302
TI - My ethical beacons: Plato, Aristotle ... and Mr. Phillips.
PMID- 11010303
TI - Who'd have thought it? Patients are putting their records online.
PMID- 11010304
TI - Automated system sends reports on abnormal findings.
PMID- 11010305
TI - How the Internet could wring $7.3 billion out of professional fees.
PMID- 11010306
TI - MR accreditation helps to assure quality service.
PMID- 11010307
TI - The Q factor. Creating a culture of quality improvement.
PMID- 11010308
TI - Audits measure practice quality of mammography.
PMID- 11010309
TI - Chemical characterization of guanidino compounds in serum.
PMID- 11010310
TI - Alcohol use and HIV pharmacotherapy.
PMID- 11010311
TI - A new pathway to product standardization.
AB - As the benefits of product standardization become more evident in improved
financial, managerial, and clinical outcomes, tools to make the process easier
will be in demand. Once a standardization program is established, e-commerce
offers tools to keep it on track.
PMID- 11010312
TI - Limited usefulness of essential trace element analyses in hair.
PMID- 11010313
TI - Optimizing cost and service in sterilization.
AB - Controlling sterilization costs is a necessity if medical device manufacturers
are to remain competitive. This article looks at ways the industry can reduce
these costs and also considers the benefits to be gained by improving
relationships with sterilization contractors.
PMID- 11010314
TI - Electron-beam sterilization. Trends and developments.
AB - The latest generation of electron-beam technology, which includes higher power
accelerators fitted with X-ray conversion, is offering manufacturers a broader
range of sterilizing options and driving market share for this method of
sterilization.
PMID- 11010315
TI - VDmax. A new method for substantiating 25 kGy.
AB - Neither of the standards for the validation and routine control of sterilization
of medical devices by ionizing radiation provides detailed guidance on how to
substantiate a 25 kGy sterilizing dose. This article describes the basis of a new
method for substantiating this dose and how the resulting procedure has been
applied in practice.
PMID- 11010316
TI - New high-frequency weldable polyolefin films.
AB - There is an increasing desire for plastic films that can be sealed using high
frequency energy. Tests on new high-frequency polyolefin film structures are
reported, which compare them with the characteristics and performance of
poly(vinyl chloride), ethylene-vinyl acetate and thermoplastic polyurethane
films.
PMID- 11010317
TI - Microsystems: applications in catheters and endoscopes.
AB - Microsystems are devices that incorporate a combination of microfluidic,
micromechanical, microoptical and microelectronic components. This is the second
article in a series that investigates the impact the technology is likely to have
on medical products during the next 10 years. This article describes how that
technology is being used to construct pressure sensors, temperature sensors,
microsurgical instruments, ultrasound transducers and imaging devices.
PMID- 11010318
TI - Notified body recommendations.
AB - This article discusses the Notified Body recommendations issued by the European
Forum of Notified Bodies Medical Devices and its subcommittee, the Notified
Bodies Recommendations Group. Most of these recommendations represent more
detailed guidance documents than the consensus statements issued by this group,
which were discussed in a previous article. Some of the recommendations form the
basis of the European-level MEDDEV guidance documents.
PMID- 11010319
TI - Towards global in vitro diagnostic standards, Part II.
AB - The first global harmonized standards for in vitro diagnostic (IVD) products are
nearing completion. Six of these standards are mandated for the IVD Directive.
Part II of this two-part article continues with a report on the current status of
these standards and reflects on the lessons learned so far from international
standardization activity.
PMID- 11010320
TI - ISO 9000:2000 revisions and their implications.
AB - The planned revision of the ISO 9000 series of standards means that all medical
device companies will have to revise their quality systems to align them with the
new ISO 9000:2000 standards. This overview outlines the changes and the factors
companies need to consider, and highlights future standards activity.
PMID- 11010321
TI - Health-care reforms in Germany.
AB - Uncertainty over the planned health-care reforms had a negative effect on the
performance of Germany's medical device industry in 1999. With hospital financing
currently at a standstill and health technology assessment on the way, this
article looks at what the reforms could mean for the industry.
PMID- 11010322
TI - Toward an information society for all: challenges in health telematics.
AB - In the emerging information society each hospital is supposed to become a node of
a complex networked information system that has to be accessible to a variety of
users. These include doctors, nurses, administrators and the patients themselves,
whose role is briefly described. This asks for a new approach to the
implementation of the interfaces of the information system, which are used to
carry out different tasks by people with different interests and computer
literacy. A new approach to the implementation of such interfaces, based on the
concepts of User interfaces for All, is briefly outlined, describing the
scientific and technical achievements in some projects partially funded by the
European Commission and the activities of the International Scientific Forum
"Towards an Information Society for All" set-up to discuss and promote the
relevant scientific concepts and technical issues.
PMID- 11010323
TI - Education and training in the MEDICOM system.
AB - MEDICOM system is a world wide telematics application for electronic commerce of
medical devices. It has been designed so as to provide the health care
professionals with a central Internet access to up-to-date information about
medical equipment from multiple manufacturers, in a particular easy and friendly
way. Moreover, the Medicom system will serve the health care professionals'
requirements for high-quality information about specific products in a form of
multimedia presentations and that of a secure communication channel with the
community of manufacturers, especially for post marketing surveillance. The
system will provide the medical staff (physicians and technicians) with
demonstrations of the operation procedures and the functioning of high-tech
equipment in a form of virtual models. Moreover, through the medicom system the
end users of medical devices can have access to on line libraries and participate
in special newsgroups. This paper discusses the architectural structure of the
MEDICOM system with emphasis to its educational and training functionality.
PMID- 11010324
TI - Mobile Medical Data (MOMEDA)--a Personalized Medical Information System.
AB - MOMEDA is a two-years project supported by the European Commission (Telematics
Applications Programme of DGXIII--Health Care Sector). The main objectives of the
project are the development of a compact personal information terminal for
hospital and home care environments that could be used by patients and a
demonstrator that allows the consulting physician to access electronic patient
record data from outside the hospital, using a hand held companion device
connected to GSM network. Special attention is paid to a Personalized Medical
Information System (PMIS) which will allow patients to access customized disease
specific information material that will enable them to fully understand in a
simple and constructive form what their medical problem is, what the planned
procedures are, what lifestyle they should follow during and after their
hospitalization, thus becoming more qualified partners in the recovery process.
Considering the fact that in most cases informed and educated patients are
usually satisfied patients when the treatment is finished, patient satisfaction
can be also accomplished. The design considerations for the PMIS system are
presented and the implementation is discussed.
PMID- 11010325
TI - Education and training in healthcare telematics.
PMID- 11010326
TI - Health informatics in the context of user ownership.
AB - Of fundamental importance to the successful implementation of health information
systems is the public and professional acceptability of their inclusion in the
healthcare process. Surprisingly, the health care sector is embracing the
informatics revolution somewhat reluctantly. Even in the areas that progress can
be seen and assessed, the rate of change is erratic and inconsistent when
compared across the spectrum of health care informatics. The mystery intensifies
if one considers the situation in global scale: despite the diversity in
approaches and models used, the reluctance perseveres. One can only suspect that
there is a common, underlying, reason which slows down the process and forces the
whole sector in being reluctant to accept change.
PMID- 11010327
TI - Evaluation of knowledge using ExaMe program on the Internet.
AB - In the paper we describe the function of the ExaMe program that serves for
evaluation of students' knowledge using Internet. Evaluation is based on the
knowledge base of a given course. Two types of evaluation tests are described.
The fixed test is appropriate for examination of students by the teacher in
computer classroom connected to Internet. By this test the evaluation is done in
the limited time period and all students are tested with the same evaluation
test. The automatic test is appropriate for self-evaluation and self-study by
students on remote places. The student can ask the ExaMe program for the test of
different difficulty levels and state the number of questions required. Finally
thee first experience with the ExaMe program in practice is given.
PMID- 11010328
TI - The continuum of health informatics educational efforts.
PMID- 11010329
TI - Health telematics applications and user acceptance from a medical student's point
of view.
AB - The goal of the workshop is dual. The first is to convince health care
professionals of health telematics applications' usefulness by demonstrating
convincing cases and the second is to examine the practical side of the story
which is education and training in health telematics. The purpose of this paper
is to present the way health telematics appeal to a medical student. After all
it's the medical student and the young practitioner whose lifetime practice will
depend on the health telematics applications that are today under development.
PMID- 11010330
TI - Thoughts about curricula in health informatics.
AB - In this contribution it is argued that it is difficult to talk of medical
informatics education since the groups that need education in this field are not
very homogeneous. Also these groups overlap. WG 1 of IMIA is in the process of
producing recommendations for curricula in medical informatics. The target groups
are defined by their career type, which is categorised using three axes:
discipline, stage of career and level of expertise. An example is given of the
knowledge requirements for medical students.
PMID- 11010331
TI - Education and training in health telematics: the critical factor of user
acceptance.
PMID- 11010332
TI - Education in biomedical engineering: experience from a European ERASMUS program.
AB - Based on recent advances in biomedical research and the developments of new
equipment and techniques, the field of Biomedical Engineering and Health Care
Telematics are currently undergoing a rapid evolution characterized by an
increasing degree of specialization. This, in turns, imposes new requirements in
advanced education, while the changing scene at European level, introduces a
major challenge for harmonization and standardization of education with a focus
on meeting the emerging needs. At the same time information technologies provide
new means and tools supporting the educational and training activities. An
initiative for the development of a multinational advanced course in Biomedical
Engineering, is implemented in the University of Patras with extended
collaboration of European Universities, providing a unique case for achievement
of excellency. In order to take full advantage of this potential, a Quality
Assurance system has been designed and implemented over the past four years,
aiming to provide the appropriate framework for mutual recognition amongst the
participating institutions. Additionally, the implementation of new telematic
tools is scheduled for the near future, in order to provide the Course with
teleconference facilities and allow a much larger number of students to remotely
attend the lectures.
PMID- 11010333
TI - Design and use of clinical ontologies: curricular goals for the education of
health-telematics professionals.
AB - In computer science, the notion of a domain ontology--a formal specification of
the concepts and of the relationships among concepts that characterize an
application are a--has received considerable attention. In human-computer
interaction, ontologies play a key role in defining the terms with which users
and computer systems communicate. Such ontologies either implicitly or explicitly
drive all dialogs between the computer and the user. In the construction of
health-telematics applications, professionals need to understand how to design
and apply domain ontologies to ensure effective communication with end-users. We
currently are revising our training program in Medical Information Sciences at
Stanford University to teach professional students in health telematics how to
develop effective domain ontologies. Instruction concerning the construction and
application of clinical domain ontologies should become an integral component of
all health telematics curricula.
PMID- 11010334
TI - Inter-university cooperation for establishing an M.Sc. course in health
informatics aims at contributing to users' acceptance of health telematics
applications.
AB - Health informatics is a recently established and important multi-disciplinary and
inter-disciplinary field that not only involves informatics but also medicine,
nursing, engineering, biology and other-related subjects. A coordination of this
field at a postgraduate level becomes important now in Europe where other
European Community programs such as the Telematics for Health Care will require
at the Fourth Framework Programme (1994-1999) and the Fifth Framework Programme
(2000-2006) adequate human resources of higher potential and knowledge. A
European M.Sc. course met all the above objectives. The curriculum was developed
according to previous experiences in similar programmes. Recently the course has
been organised on the basis of an Inter-University nature with the participation
of 5 Greek Universities. The paper aims at providing a description of the new
academic programme and a brief evaluation of the implementation phase.
PMID- 11010335
TI - Role of the EU commission for pushing the user acceptance of the health
telematics applications.
PMID- 11010336
TI - User acceptance by individuals of health telematics from distributed EPRs
associated with knowledge couplers.
AB - The patient in a hospital bed is also a private individual that might access his
or her own Electronic Patient Record (EPR) in association with additional tools
that are able to show critical up-to-date knowledge about diagnoses, clinical
investigations or treatments. The distributed EPRs are shown here in full
production with the DOMED application of DIOGENE 2. Besides, in order to
facilitate an easier understanding of the EPRs by the patient, the HON Web Site
services are at his or her disposal in this respect at the same terminal.
PMID- 11010337
TI - Utilising multimedia for training merchant mariners as paramedics.
AB - MERMAID is a telemedicine project with global reach and a 24-hour, multilingual
capability. It aspires to provide a model for the provision of health care
services based on the electronic transmission of medical information, via ISDN
based videoconferencing. This model is not limited to medical diagnostics but it
encompasses all cases where the actual delivery of health care services involves
a patient who is not located where the provider is. Its implementation requires
the commissioning of an expensive telecommunications infrastructure and the
exploration of a number of solutions. In fact, all categories of telemedical
applications are considered while the full range of network choices is explored
in terms of the cost/performance tradeoffs inherent to them and the developmental
stage each of these options occupies in its life cycle. MERMAID utilises advanced
land based line transmission technologies to aid the remote patient by making
available the specialty care best suited to each particular case. Finally, the
development of programme modules for training and education of the seafarers in
the use of the MERMAID medical communications system is given top priority as
such modules constitute the firmest basis for the promotion of proper practice of
telemedicine at sea.
PMID- 11010338
TI - Developing new competencies in healthcare practitioners in the field.
AB - The Life-long Learning concept is one which is appropriate for those who have (or
create) the opportunities to develop their competencies once they are in an
operational role. All models of healthcare delivery and management are VOLATILE
and therefore the way of addressing new competencies cannot be prescriptive or
stand still for too long, but the concepts do endure. Learning, in order to 'keep
up to date' is very necessary--technology, new clinical practices and
interventions, new drug interactions, increased patient demands ... all add to
the need to move with the times. This paper addresses some of the issues
surrounding this challenge in the domain of informatics in support of healthcare
delivery and management.
PMID- 11010339
TI - Learning just-in-time in medical informatics.
AB - Just-in-time learning (JITL) methodology has been applied to many areas of
knowledge acquisition and dissemination. The paradigm is a challenge to the
traditional classroom course-oriented approach with the aim to shorten the
learning time, increasing the efficiency of the learning process, improve
availability and save money. The information technology tools and platforms have
been heavily involved to develop and deliver JITL. This paper discusses the main
characteristics of JITL with regard to its implementation to teaching Medical
Informatics.
PMID- 11010340
TI - Education and training in health telematics.
PMID- 11010341
TI - Prospects of medical informatics education in Greece: can we bridge the gap?
AB - Medical Informatics education is a complex task,, since it aims in educating
inhomogeneous groups of people coming from different disciplines. In Greece,
recently considerable advancements in the medical informatics education field are
made. These advancements aim in bridging gaps in various areas of MI users
interactions. In particular, an overview of the strategy of the Greek ministry of
education shall be given, some examples of MI related educational programs shall
be referred to, and finally the MI educational structure used in the Aristotelian
University shall be presented in detail, laying out the strategy of this
University for bridging various types of gaps.
PMID- 11010342
TI - Designing for interaction quality in health telematics.
AB - This paper focuses on emerging Human Computer Interaction (HCI) challenges in the
context of Health Telematics. Specifically, assumptions in traditional approaches
to product and process quality are discussed, in order to unfold the reasons
behind the loose and partial insight offered to the design of technology for the
broadest possible end-user population. The premises of "Universal Design" are
briefly discussed and the concept of "User Interfaces for All" is presented, as
an articulation of Universal Design in the area of HCI. Following this, the paper
discusses how such a perspective improves upon conventional methods and tools for
HCI design and presents some of its relative merits in the context of Health
Telematics.
PMID- 11010343
TI - 21st century communication age.
PMID- 11010344
TI - Use of multiple media and breast cancer screening: an introduction.
PMID- 11010345
TI - Effect of media coverage and physician advice on utilization of breast cancer
screening by women 40 years and older.
AB - The purpose of this study is to examine the relative importance of media coverage
and physician advice on the decision of women 40 years and older to obtain a
mammogram. Five theoretical models, by which media coverage and physician advice
may interact to affect individual health behavior, are presented. These models
are tested with time-series regression analysis based on national-level data on
mammography utilization and physician advice from the Behavioral Risk Factor
Surveillance System (BRFSS) and content analysis of mammography-related national
news coverage. Results suggest that although physician advice plays a key role in
women's decisions to have mammograms, media coverage of mammography screening
also contributes to mammography utilization by women. In particular, media
coverage seems to be important for women who do not have regular contact with a
physician or access to physicians. A possible conclusion is that mass media and
physician advice complement one another in persuading individuals to adopt
preventive health behavior.
PMID- 11010346
TI - Experiences of women with breast cancer: exchanging social support over the CHESS
computer network.
AB - Using an existential-phenomenological approach, this paper describes how women
with breast cancer experience the giving and receiving of social support in a
computer-mediated context. Women viewed their experiences with the computer
mediated support group as an additional and unique source of support in facing
their illness. Anonymity within the support group fostered equalized
participation and allowed women to communicate in ways that would have been more
difficult in a face-to-face context. The asynchronous communication was a
frustration to some participants, but some indicated that the format allowed for
more thoughtful interaction. Motivations for seeking social support appeared to
be a dynamic process, with a consistent progression from a position of receiving
support to that of giving support. The primary benefits women received from
participation in the group were communicating with other people who shared
similar problems and helping others, which allowed them to change their focus
from a preoccupation with their own sickness to thinking of others. Consistent
with past research is the finding that women in this study expressed that social
support is a multidimensional phenomenon and that their computer-mediated support
group provided abundant emotional support, encouragement, and informational
support. Excerpts from the phenomenological interviews are used to review and
highlight key theoretical concepts from the research literatures on computer
mediated communication, social support, and the psychosocial needs of women with
breast cancer.
PMID- 11010347
TI - Cigarette advertising to counter New Year's resolutions.
AB - One process through which tobacco advertising may work is by reducing rates of
quitting. Theories of addiction support the notion that relapse can be prompted
by environmental cues. Further, because withdrawal symptoms occur over a
predictable time frame, and because the most popular time to quit smoking is the
beginning of the year, as a New Year's resolution, tobacco companies can make use
of advertising to remind quitters of their need to smoke. Study 1 examined
advertising in 10 popular magazines. It found a higher number of ads in January
and February than the rest of the year after 1984. Study 2 examined cigarette
advertising on the back cover of 10 other popular magazines. This study also
found a higher rate of cigarette advertisements in January and February than for
the rest of the year. The results suggest that cigarette marketers may be
attempting to preempt quitting by cuing smoking behavior.
PMID- 11010348
TI - Church-based telephone mammography counseling with peer counselors.
AB - Little is published about step-by-step implementation of telephone counseling
interventions to promote community-based health activities. This article
describes the authors' experience of implementing a church-based telephone
mammography counseling intervention with peer counselors representing three
principal racial or ethnic groups: African American, Latino, and Anglo (White).
Twenty-six women from 12 churches in the Los Angeles area were recruited and
trained to deliver the counseling annually over a two-year period to 570 women
participants who were recruited from participating churches (n = 15). The
counseling sessions were conducted from church-based telephone centers in key
geographic locations in our program area. Training and supervision proved
challenging: most of the Latino counselors had fewer than seven years of
education and spoke only Spanish, while most of the other counselors had at least
some college and spoke only English. Culturally specific and small group
interactions, role plays, and a more modular approach to training were the most
effective ways to enhance counselors' skills. Latina participants' mammography
adherence rates were lowest, and their barriers reflected their low socioeconomic
status; as Latina counselors shared basic information about mammograms and where
to obtain them at little or no cost, the counseling exchanges tended to be
nonconflictive and supportive. Black and White participants were generally more
knowledgeable and adherent with screening guidelines than Latinas. We found that
it was possible to implement this intervention with diverse groups and conclude
with lessons learned that may inform others considering such a strategy.
PMID- 11010349
TI - Communications for HIV/AIDS prevention, care, and support: contexts for
individual and social change. Introduction.
PMID- 11010350
TI - Toward a new communications framework for HIV/AIDS.
AB - In response to the overwhelming burden of new cases of human immunodeficiency
virus (HIV) in Africa, Asia, Latin America, and the Caribbean, the Joint United
Nations Programme on HIV/AIDS (UNAIDS), in 1997, initiated a project to examine
the application of existing communication theories/models to HIV/acquired immune
deficiency virus (AIDS) prevention and care in these regions. In the past 2
years, 103 leading researchers and practitioners from different parts of the
world were invited by the UNAIDS to participate in one of five consultative
workshops designed to review these theories/models and rethink their adequacy for
Africa, Asia, Latin America, and the Caribbean. A new communications framework
for HIV/AIDS was developed to move from a focus on the individual to a focus on
five domains of "contexts" that influence behaviors: government policy,
socioeconomic status (SES), culture, gender relations, and spirituality.
PMID- 11010351
TI - From government policy to community-based communication strategies in Africa:
lessons from Senegal and Uganda.
PMID- 11010352
TI - Odo-Ya project: HIV/AIDS prevention in the context of Afro-Brazilian religion.
PMID- 11010353
TI - Gender and HIV/AIDS in Africa--our hope lies in the future.
PMID- 11010354
TI - Social and economic factors in an integrated behavioral and societal approach to
communications in HIV/AIDS.
AB - Health communication scholars have tried to understand how individuals process
information and have identified the factors that contribute to appropriate
behavior change. Some of these theorists have, implicitly or explicitly, assumed
that if individuals were provided with the "right" information they would adopt
the recommended behavior. Some others have endorsed the need to provide
behavioral skills along with information so that individuals are able to carry
out the desired behavior. Both approaches, however, are concerned with individual
behavior change. Sociodemographic variables like class, gender, and race have
seldom figured in sociopsychological analyses in the AIDS context. Limited
attention has been paid to the manner in which political, economic, and social
variables have constrained or enabled individual behavior related to AIDS. In
this article, the various sociopsychological theories/models that inform AIDS
prevention are delineated; the sociopsychological approaches in the context of
class, race, and gender issues are critiqued; and an analytical framework that
integrates behavioral and societal level variables to guide policy interventions
is provided.
PMID- 11010355
TI - HIV/AIDS communication campaigns: progress and prospects.
AB - The mass media have been the primary method for disseminating human
immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
prevention messages worldwide. In this article, we update previous reviews by
systematically examining published articles (n = 41) of empirical evaluations of
international HIV/AIDS prevention campaigns. Of the 41 studies identified, 17
countries are represented. In this review, we examine six components related to
media campaign design and evaluation: target audience, communication channel(s),
message content, campaign theme, exposure, and outcomes. Of the studies included
in this sample, each one described the target audience; 93% reported on channel
selection; 75% described message content; 63% mentioned a campaign theme; and 62%
documented campaign exposure. We investigate also the extent to which HIV/AIDS
prevention efforts have moved beyond media campaigns to comprehensive
communitywide programs. We conclude that HIV/AIDS prevention efforts would
benefit from: (1) better reporting of media campaign components and outcomes, (2)
more systematic evaluation, (3) greater integration of theory, and (4) increased
attention to communitywide intervention strategies.
PMID- 11010356
TI - Coping in cyberspace: the impact of Internet use on the ability of HIV-positive
individuals to deal with their illness.
AB - The human immunodeficiency virus (HIV) poses one of the greatest health threats
of modern times. The Internet provides unparalleled access to resources that can
assist individuals coping with HIV infection. Despite the promise of online
resources to help individuals manage and cope with their illness, few studies
have investigated the impact of their use. Those that have looked primarily at
Internet use from a group perspective. These studies were usually "bounded" as
well, focusing on electronic support groups or highly structured computer-based
support systems that offer select users prescribed resource options. Little is
known about how individuals who are "on their own"--without access to these
services--use the vast, unstructured array of resources available through the
Internet. The purpose of this study was to investigate the impact of Internet use
on the coping ability of HIV-positive individuals. This research study employed a
descriptive qualitative design that used indepth, semi structured, face-to-face
interviews for data collection. The sample of 10 purposefully selected HIV
positive individuals reflected diversity in gender, age, race, education,
employment, number of years living with HIV, and Internet use. Data analysis
guided by the constant comparative method revealed that the impact of Internet
use on coping ability involved three themes: The Internet promotes empowerment,
augments social support, and facilitates helping others.
PMID- 11010357
TI - A critical assessment of theories/models used in health communication for
HIV/AIDS.
AB - Most theories and models used to develop human immunodeficiency virus
(HIV)/acquired immune deficiency syndrome (AIDS) communication are based on
social psychology that emphasizes individualism. Researchers including
communication and health scholars are now questioning the presumed global
relevance of these models and thus the need to develop innovative theories and
models that take into account regional contexts. In this paper, we discuss the
commonly used theories and models in HIV/AIDS communication. Furthermore, we
argue that the flaws in the application of the commonly used "classical" models
in health communication are because of contextual differences in locations where
these models are applied. That is to say that these theories and models are being
applied in contexts for which they were not designed. For example, the
differences in health behaviors are often the function of culture. Therefore,
culture should be viewed for its strength and not always as a barrier. The
metaphorical coupling of "culture" and "barrier" needs to be exposed,
deconstructed, and reconstructed so that new, positive, cultural linkages can be
forged. The HIV/AIDS pandemic has served as a flashpoint to either highlight the
importance or deny the relevance of theories and models while at the same time
addressing the importance of culture in the development and implementation of
communication programs.
PMID- 11010358
TI - Peer promotion programs and social networks in Ghana: methods for monitoring and
evaluating AIDS prevention and reproductive health programs among adolescents and
young adults.
AB - This article summarizes the observations and lessons learned regarding the
application of human immunodeficiency virus (HIV)/acquired immune deficiency
syndrome (AIDS) prevention and reproductive health evaluation methodologies in
the context of adolescent and young adult populations and discusses the use of
peer network evaluation to understand the dynamics of peer promotion. To examine
the interpersonal communication process of peer education, this study tested a
new approach using multiple semistructured interviews and network analysis to
collect data on 106 peer educators and 526 of their contacts. These evaluation
activities were conducted at three sites in Ghana during April 1998, in both
periurban and rural locations in both in-school and out-of-school settings. By
evaluating the social networks of peer educators it was possible to gain a better
understanding of the process of peer education in terms of (a) defining the
composition of peer contacts, (b) identifying the social norms that play a
critical role in youth decision making, and (c) observing the range of messages
and services transmitted during peer education. The objective of this paper is to
disseminate the experience of the Center for Education and Development of
Population Activities (CEDPA) and Focus on Young Adult's cooperative development
of evaluation methodologies for peer promotion and to highlight utilization of
these methodologies in a case study in Ghana. The results will be discussed in
terms of their possible implications for program managers, researchers, and
international agencies.
PMID- 11010359
TI - Entertainment-education and HIV/AIDS prevention: a field experiment in Tanzania.
AB - Entertainment-education is the process of designing and implementing an
entertainment program to increase audience members' knowledge about a social
issue, create more favorable attitudes, and change their overt behaviors
regarding the social issue. The results of a field experiment in Tanzania to
measure the effects of a long-running entertainment-education radio soap opera,
Twende na Wakati (Let's Go with the Times), on knowledge, attitudes, and adoption
of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
prevention behaviors are presented. Multiple independent measures of effects and
the experimental design of this study confer strong internal and external
validity regarding the results of this investigation. The effects of the radio
program in Tanzania include (1) a reduction in the number of sexual partners by
both men and women, and (2) increased condom adoption. The radio soap opera
influenced these behavioral variables through certain intervening variables,
including (1) self-perception of risk of contracting HIV/AIDS, (2) self-efficacy
with respect to preventing HIV/AIDS, (3) interpersonal communication about
HIV/AIDS, and (4) identification with, and role modeling of, the primary
characters in the radio soap opera.
PMID- 11010360
TI - Protecting your paperless medical record system requires addressing risks.
PMID- 11010361
TI - Terrorism: haz-mat bug for the new millennium.
PMID- 11010362
TI - Developing a safe, effective restraint policy.
PMID- 11010363
TI - Hot issues in clinical research.
PMID- 11010364
TI - Evaluating your performance improvement system using a Baldrige-based self
assessment.
PMID- 11010365
TI - The importance of informed consent in medical research.
PMID- 11010366
TI - Adoption of electronic medical records as a technology innovation for ambulatory
care at the Medical University of South Carolina.
AB - The study described in this article measured and compared the attitudes of groups
of Medical University of South Carolina (MUSC) ambulatory care staff and
physicians toward adopting an electronic medical record (EMR) system, using the
Perceived Characteristics of Innovating (PCI) scales developed by Moore and
Benbasat (1991). The PCI scale scores were compared by professional group and by
clinic location. The overall findings of this study were that potential users of
the ambulatory care EMR at MUSC had generally positive or neutral attitudes
toward the system. There were a number of significant differences noted among the
professional groups, particularly between the physician groups and other groups.
The physician groups had less positive feelings than the other groups did. There
were few significant differences noted for comparisons by clinic location.
PMID- 11010367
TI - Cancer surveillance using data warehousing, data mining, and decision support
systems.
AB - This article discusses how data warehousing, data mining, and decision support
systems can reduce the national cancer burden or the oral complications of cancer
therapies, especially as related to oral and pharyngeal cancers. An information
system is presented that will deliver the necessary information technology to
clinical, administrative, and policy researchers and analysts in an effective and
efficient manner. The system will deliver the technology and knowledge that users
need to readily: (1) organize relevant claims data, (2) detect cancer patterns in
general and special populations, (3) formulate models that explain the patterns,
and (4) evaluate the efficacy of specified treatments and interventions with the
formulations. Such a system can be developed through a proven adaptive design
strategy, and the implemented system can be tested on State of Maryland Medicaid
data (which includes women, minorities, and children).
PMID- 11010368
TI - Organizational status of quality assurance and end-user perceptions of
information technology for information management.
AB - This article investigates the relationship between quality assurance (QA) and
perceptions of the importance of information technology (IT) for information
management in the health care industry. This issue is important because effective
information management is recognized as a necessary condition for quality
management. The unit of analysis of the article is the health care functional
department. Data from 34 health care departments were collected and used for the
analysis. Four specific hypotheses were proposed and tested. Our results suggest
that end-user perceptions of the importance of IT for information management
depends on formalization of QA, perceived importance of QA, time since QA was
embraced, and number of people in the QA function.
PMID- 11010369
TI - Big issues, small systems: managing with information in medical research.
AB - This subject of this article is the design of a database system for handling
files related to the work of the Molecular Genetics Department of the
International Blood Group Reference Laboratory. It examines specialist
information needs identified within this organization and it indicates how the
design of the Rhesus Information Tracking System was able to meet current needs.
Rapid Applications Development prototyping forms the basis of the investigation,
linked to interview, questionnaire, and observation techniques in order to
establish requirements for interoperability. In particular, the place of this
specialist database within the much broader information strategy of the National
Blood Service will be examined. This unique situation is analogous to management
activities in broader environments and a number of generic issues are highlighted
by the research.
PMID- 11010370
TI - The disability assessment database model.
AB - Collecting disability-related information in order to prevent and treat specific
disabilities is important and necessary, but does it meet the major needs of
individuals with disabilities? This article presents preliminary research
performed to assess those needs as well as a Disability-service Assessment
Database (DAD) model. This model provides local disability service data and
surveys users so that their input is used to modify existing data. The content of
the database and Web site are discussed and diagramed. A major goal of the DAD is
to serve as a model to other communities.
PMID- 11010371
TI - Health information management in the rehabilitation environment: the Easter Seal
Society of western Pennsylvania.
AB - Health information management functions are becoming more automated as facilities
move toward the use of computerized health records. Nonprofit human services
organizations are investigating the benefits of automating manual systems to
determine the impact of automated systems on productivity, documentation, cost
effectiveness, and quality of care. Management systems that integrate billing and
clinical functions can be designed to meet the specific needs of any type of
agency, such as rehabilitation agencies. This article discusses the initial
implementation of such a system and its impact on staff and their work
procedures. Also discussed is the agency's future vision of its computerized
client management system.
PMID- 11010372
TI - Managing the learning and work of new information technology users.
AB - The information technology revolution has transformed work from modest-paced
serial processes to complex, fast-paced networked ones that depend not only on
the technology but also on skilled and effective users of the technology. This
evolution has woven a complex quilt of interdependencies among new information
technologies, new users of those technologies, new skills required, new
information management policies and procedures, and new opportunities. We must
impose a new structure for managing the learning and work of new users, their
tolerance of complexity and continuous learning, value-added usability,
minimization of human error, and new support services for deployment,
administration, and help.
PMID- 11010373
TI - Preparing for a decision support system.
AB - The increasing pressure to reduce costs and improve outcomes is driving the
health care industry to view information as a competitive advantage. Timely
information is required to help reduce inefficiencies and improve patient care.
Numerous disparate operational or transactional information systems with
inconsistent and often conflicting data are no longer adequate to meet the
information needs of integrated care delivery systems and networks in competitive
managed care environments. This article reviews decision support system
characteristics and describes a process to assess the preparedness of an
organization to implement and use decision support systems to achieve a more
effective, information-based decision process. Decision support tools included in
this article range from reports to data mining.
PMID- 11010374
TI - Justifying cardiac transports.
PMID- 11010375
TI - Recent progress in advanced cardiac life support.
AB - The revised guidelines for advanced cardiac life support (ACLS) from the American
Heart Association are anticipated in the fall of 2000. Although dramatic changes
in the approach to adult basic and ACLS are not anticipated, several
controversies and new drugs on the horizon may radically change our approach to
emergent cardiac resuscitation. This article features some of the evolving
thinking on the emergent treatment of the adult with ventricular fibrillation or
ventricular tachycardia, the critical rhythms seen in most cases of acute cardiac
distress. Approaches to airway therapy drug administration and new agents also
are described.
PMID- 11010376
TI - Reperfusion of acute coronary syndromes and myocardial infarction.
PMID- 11010377
TI - Chest pain: current concepts and implications for critical care transport.
PMID- 11010378
TI - Oxygenation/ventilation of transported intubated adult patients: a national
survey of organizational practices.
AB - INTRODUCTION: Transporting intubated patients is common among ground and air
crews, and providing adequate oxygenation/ventilation through transport
ventilators (TV) or manual ventilation (MV) is clinically challenging. However,
very little data chronicle service or practice patterns of
oxygenation/ventilation within the industry. METHODS: During February 1998, a
national sample of 250 air transport agencies was surveyed regarding activities
and services surrounding this population of transported patients. One-hundred
ninety-three surveys (77%) were returned. RESULTS: Approximately 40% of
responding agencies use rotor-wing transportation only. Various combinations of
rotor-, fixed-wing, and critical care ground transport were reported among the
sample. Crew configuration consisted primarily of RN/EMT-P (75%). For pre
hospital intubated patients, MV alone (37.3%), TV alone (10.9%), or a combination
of MV and TV (43.5%) was used, depending on transport circumstances. Programs not
involved in pre-hospital transports accounted for 8.3% of returned surveys.
Interfacility transports used MV (6.8%), TV (39.4%), and a combination (53.4%).
One respondent did not answer the question, accounting for 0.4% of the returned
surveys. More than 75% of programs monitored oxygenation/ventilation during
transport. Usually some combination of pulse oximetry and CO2 monitoring was
used. More than half (59%) of reporting agencies transport more than 80 intubated
adults each year. CONCLUSION: Considerable variation exists in practices
involving the transport of intubated patients.
PMID- 11010379
TI - Pilot study for predicting appropriate use of air medical helicopters. Part 1:
Interfacility transports.
PMID- 11010380
TI - New concepts in health benefits. Part 3. Employee incentives.
PMID- 11010381
TI - Variety is the spice of a great workforce.
PMID- 11010382
TI - There's no place like home ... for today's teleworkers.
PMID- 11010383
TI - Are you paying too much for lab tests?
PMID- 11010385
TI - DataWatch. Employers ask less about health care.
PMID- 11010384
TI - Strength in service.
PMID- 11010386
TI - Consumerism in the financial services industry: lessons for managed care.
AB - Managed care today is being shaped by the emergence of a savvier, better informed
health care consumer. Facing a strikingly similar consumer movement over the past
two decades, the banking industry experienced a market transformation that holds
important lessons for managed care. Nontraditional entrants in the financial
services industry, offering focused "monoline" products and services closely
analogous to "carve-out" providers in health care, targeted rising consumer
demands and stronger preferences. Banks in time answered these formidable new
competitive forces with innovative consolidation and globalization strategies.
The most successful initiatives in healthcare, as in banking, will focus on
satisfying the consumer's hunger for information, improved levels of service, and
enhanced outcomes. Managed care plans may play a lead role in accelerating the
impact of consumerism by bridging the disconnect between patients and their
purchasing decisions.
PMID- 11010387
TI - Customer value & business success in the 21st century.
AB - Many health care organizations are realizing the importance of understanding the
needs and expectations of customers and prospective customers, coupled with
developing services that best meet and exceed those expectations. These concepts
represent an innovative yet fundamental approach to building success beyond the
clinical aspects. To create, build on, and measure the "customer value factor" in
its bottom line, health care organizations must (1) understand how meeting and
exceeding the needs and expectations of customers will become the most
significant differentiator of true business value, (2) learn how to develop
realistic, measurable, and successful customer value processes within complex
organizations, (3) understand how customer value can link with the power of
strategic communications to become the new currency for the next millennium.
PMID- 11010388
TI - Customer service: the key to remaining competitive in managed care.
AB - The health care industry is undergoing a rapid transformation to meet the ever
increasing needs and demands of its patient population. Employers and managed
care organizations are demanding better service and higher quality care, while
providers are trying to tackle reimbursement cutbacks, streamlining of services,
and serving a diverse population. Providers have begun to realize that to
overcome these obstacles and meet the needs of their health plans and consumers,
they must focus on the demands of their customers. Health care organizations have
found they can meet the demands of both the consumer and the managed care
industry through initiating and maintaining a customer service program. This
essay explains the importance of customer service and its link to success in the
managed care environment.
PMID- 11010389
TI - The implementation of clinical guidelines in a managed care setting: implications
for children with special health care needs.
AB - OVERVIEW: The project tracked the development and implementation of a pediatric
asthma guideline to determine its usefulness as a quality assurance mechanism for
children with special health care needs. METHODS: Interviews were conducted with
clinic staff to gather descriptive information about guideline implementation at
owned clinics within a large HMO. RESULTS: Providers developed multiple
implementation strategies emphasizing patient/family education. Service
coordination within the health plan was well established, while coordination of
services beyond the health plan was less clearly related to guideline
implementation. CONCLUSION: Guideline implementation appeared to be a highly
variable process. Clinical guidelines alone may not be sufficient tools of
quality assurance for children with chronic or complex conditions.
PMID- 11010390
TI - Health plan responses to Medicaid managed care policy in New York City.
AB - Nearly all states in the United States have instituted managed care programs to
serve Medicaid recipients and are developing policies to increase program
participation. State practices regarding managed care contracting, premiums, and
enrollment have implications for whether managed care plans will respond in a
manner consistent with overall state policy objectives for the Medicaid managed
care program. The experience of expanding the Medicaid managed care program in
New York City, where the number of Medicaid beneficiaries exceeds the number in
all but three states, has provided an interesting opportunity to look at the
relationship between Medicaid managed care policy and plan enrollment. This paper
analyzes trends in Medicaid managed care enrollment in New York City from January
1991 to September 1998, a period of critical changes in Medicaid managed care
policy in New York.
PMID- 11010391
TI - HMOs serving rural areas: experiences with HMO accreditation and HEDIS reporting.
AB - This article explores the reasons why two groups of health maintenance
organizations (HMOs) that serve rural areas have chosen to apply or not to apply
for National Committee for Quality Assurance (NCQA) accreditation, and their
future plans regarding accreditation. It also describes the challenges faced by
HMOs serving rural areas in meeting NCQA accreditation standards and collecting
Health Plan Employer Data and Information Set (HEDIS) data. A number of
accredited HMOs cited positive benefits of the accreditation process, and most
HMOs plan to apply or reapply for accreditation in the near future. Several HMOs
identified challenges with accreditation standards, and the majority reported
difficulty collecting some HEDIS measures. The HMOs identified a number of
accreditation and HEDIS issues that are more problematic in rural areas.
PMID- 11010392
TI - Ten top reasons teams become dysfunctional.
PMID- 11010393
TI - The evolution of retirement: results of the 1999 Retirement Confidence Survey.
AB - The ninth annual Retirement Confidence Survey (RCS) shows continued evidence of
progress in the drive for retirement income security for American workers.
However, there are still hurdles to overcome. The RCS tracks Americans'
retirement planning and saving behavior and their confidence regarding various
aspects of their retirement. It also categorizes workers and retirees into
distinct groups based on their individual views on retirement, retirement
planning, and saving. The retirement envisioned by today's workers looks
different in many respects from that now experienced by current retirees. Today's
workers expect to work longer than current retirees actually worked before
retiring--and many say they plan to work for pay after they retire. Twenty-four
percent of workers reported that they are very confident they will have enough
money to live comfortably in retirement, and 45 percent reported that they are
somewhat confident. However, there are indications that many may be falsely
confident. The good news is that 70 percent of Americans are saving for
retirement, and a growing percentage (49 percent) are going further and
determining how much they need to save to fund their retirement. The bad news is
that 30 percent of Americans have not begun to save for their retirement, and 51
percent have never tried to determine how much they need to save. Employers play
a major role in ensuring adequate retirement preparation. Forty percent of all
workers said they expect that money provided by their employer will be a major
source of retirement income. Forty-six percent expect the money they put into a
retirement plan at work to be a major source of income. The availability of a
retirement plan at work is credited by 48 percent of savers as motivation to
save. While worker education is a point of emphasis among both employers and
policymakers, more remains to be done. For example, 59 percent of workers expect
to be eligible for full Social Security benefits sooner than they actually will
be, and an additional 19 percent admit they do not know when they will be
eligible. There is evidence that education can have an impact on individual
behavior. Forty percent of workers receiving educational material at work in the
last year said that information caused them to begin saving (19 percent) or
resume saving (21 percent) for retirement, while 40 percent said they changed the
amount they were contributing to a retirement savings plan and 41 percent changed
the allocation of their money in a retirement savings plan.
PMID- 11010394
TI - Sources of health insurance and characteristics of the uninsured: analysis of the
March 1999 Current Population Survey.
AB - This Issue Brief provides summary data on the insured and uninsured populations
in the nation and in each state. It discusses the characteristics most closely
related to an individual's health insurance status. Based on EBRI estimates from
the March 1999 Current Population Survey (CPS), it represents 1998 data--the most
recent data available. In 1998, 194.7 million nonelderly Americans--81.6 percent-
had some form of health insurance. More than 64 percent had it through an
employment-based health plan; 6.5 percent purchased it on their own; and 14.3
percent were covered by a public program, mostly through Medicaid (10.4 percent).
In 1998, 18.4 percent of the nonelderly population was uninsured (43.9 million
people), compared with 14.8 percent in 1987. The percentage of uninsured
Americans has generally been increasing since at least 1987, although the
percentage uninsured in 1998 was not statistically different from the percentage
uninsured in 1997 (18.3 percent). The increase in the uninsured prior to 1993 can
be attributed to the erosion of employment-based health insurance. However, since
1993, the percentage of nonelderly Americans covered by an employment-based
health plan has increased from 63.5 percent to 64.9 percent. The decline in
public sources of health insurance would mostly explain the recent increase in
the uninsured. For example, between 1994 and 1998 the percentage of nonelderly
Americans covered by CHAMPUS/CHAMPVA declined from 3.8 percent to 2.9 percent, in
large part due to downsizing in the military. Similarly, between 1993 and 1998,
the percentage of nonelderly Americans covered by Medicaid declined from 12.7
percent to 10.4 percent as people left welfare. The increase in employment-based
coverage since 1994 was due mainly to a higher likelihood that children were
covered by an employment-based health plan. Between 1994 and 1998, the percentage
of children covered by an employment-based health plan increased from 58.1
percent to 60.2 percent. For adults, it increased less than one percentage point,
from 66.1 percent to 66.9 percent. Adults started to realize gains in employment
based health insurance between 1997 and 1998. Between 1994 and 1997, the
percentage of working adults with employment-based health insurance coverage held
steady at roughly 72.3 percent. During this period, health care cost inflation
was essentially nonexistent. However, between 1997 and 1998, the percentage of
working adults with employment-based health insurance increased from 72.2 percent
to 72.8 percent, despite the apparent return of health care cost inflation in
1998. It is likely that the changing composition of the labor force accounted for
some of the increase in employment-based coverage.
PMID- 11010395
TI - 401(k) plan asset allocation, account balances, and loan activity in 1998.
AB - The Employee Benefit Research Institute (EBRI) and the Investment Company
Institute (ICI) have been collaborating for the past three years to collect data
on participants in 401(k) plans. This effort, known as the EBRI/ICI Participant
Directed Retirement Plan Data Collection Project, has obtained data for 401(k)
plan participants from certain of EBRI and ICI members serving as plan record
keepers and administrators. The report includes 1998 information on 7.9 million
active participants in 30,102 plans holding nearly $372 billion in assets. The
data include demographic information, annual contributions, plan balances, asset
allocation, and loans, and are broadly representative of the universe of 401(k)
plans. The database also includes three years of longitudinal information on
approximately 3.3 million participants. Key findings include: For all 401(k)
participants in the 1998 EBRI/ICI database, almost three-quarters of plan
balances are invested directly or indirectly in equity securities. Specifically,
49.8 percent of total plan balances are invested in equity funds, 17.7 percent in
company stock, 11.4 percent in guaranteed investment contracts (GICs), 8.4
percent in balanced funds, 6.1 percent in bond funds, 4.7 percent in money funds,
and 0.3 percent in other stable value funds. Participant asset allocation varies
considerably with age. Younger participants tend to favor equity funds, while
older participants are more disposed to invest in GICs and bond funds. On
average, participants in their 20s have 62.1 percent of their account balances
invested in equity funds, in contrast to 39.8 percent for those in their 60s.
Participants in their 20s invest 4.7 percent of their assets in GICs, while those
in their 60s invest 20.6 percent. Bond funds, which represent 4.7 percent of the
assets of participants in their 20s, amount to 9.0 percent of the assets of
participants in their 60s. Investment options offered by 401(k) plans appear to
influence asset allocation. For example, the addition of company stock
substantially reduces the allocation to equity funds and the addition of GICs
lowers allocations to bond and money funds. The average account balance (net of
plan loans) for all participants was $47,004 at year-end 1998, which is 26
percent higher than the average account balance at year-end 1996. The median
account balance was $13,038 at year-end 1998. The balances, however, represent
only amounts with current employers and do not include amounts remaining in the
plans of prior employers. The average balances of older workers with long tenure
indicate that a mature 401(k) plan program will produce substantial account
balances. For example, individuals in their 60s with at least 30 years of tenure
have average account balances in excess of $185,000. The ratio of account balance
to 1998 salary varies with salary, increasing slightly as earnings rise from
$20,001 to $80,000, and falling a bit for salaries greater than $80,000. The
increase in ratio likely reflects a greater propensity of higher-income
participants to save, whereas the decline after $80,000 results from contribution
and nondiscrimination rule constraints.
PMID- 11010396
TI - The working uninsured: who they are, how they have changed, and the consequences
of being uninsured--with presidential candidate proposals outlined.
AB - This Issue Brief presents data on workers who do not have health insurance. It
offers a description of this population, discusses how this population has
changed over time, and reviews the consequences of being uninsured. Also included
is a description of the 2000 presidential candidates' proposals to reduce the
number of uninsured Americans. The percentage of workers without any form of
health insurance has been increasing since at least 1987. In 1998, 18.1 percent
of workers were uninsured, up from 14.6 percent in 1987, although most of the
increase occurred prior to 1993. Uninsured adult workers made up 56 percent of
the uninsured population in 1998. In all, 83.2 percent of the 43.9 million
uninsured Americans were in a family with a working family head. The working
uninsured are heavily concentrated in certain segments of the population. In
1998, 53 percent of uninsured workers were under age 35, 58 percent were male, 57
percent were white, nearly 90 percent had not received a college diploma, 78
percent worked full time, 20 percent worked in the service industry, 60 percent
were employed in small firms or were self-employed, 42 percent earned $7.00 or
less per hour, and 99 percent earned less than $50,000 per year. The likelihood
of being uninsured increased substantially for certain groups of workers between
1987 and 1998. The highest rates of increase were found among workers ages 55-64
(44 percent), in families at or above 400 percent of the federal poverty level
(61 percent), in the public sector (34 percent), in the largest firms (53
percent), with hourly wages of $15.00 or more (50 percent), with annual income
between $25,000 and $75,000 (100 percent), and with retirement plans (112
percent). Health insurance makes a difference in health status and access to
health care services. Data show that uninsured workers are more likely than
insured workers to report that their health status is fair or poor. Compared with
insured workers, uninsured workers were more likely to receive health care in a
hospital or emergency room, and were less likely to receive it in an office-based
setting. Both the major-party presidential candidates, Vice President Al Gore and
Texas Gov. George W. Bush, have put forth proposals to reduce the number of
uninsured Americans. While both candidates' proposals recognize that the bulk of
uninsured Americans are either children or workers employed by small firms, the
proposed strategies to deal with these populations are incremental, and are
unlikely to have a substantial impact on the number of uninsured Americans.
PMID- 11010398
TI - Introduction to Employment 101: hiring the new grad.
PMID- 11010397
TI - The maturing of consumerism.
PMID- 11010399
TI - Customer service training ... the creative way!
PMID- 11010400
TI - The next generation in health care.
PMID- 11010401
TI - A commitment to satisfied customers.
PMID- 11010402
TI - Look closely at responsibilities.
PMID- 11010403
TI - House GOP unveils family safety priorities.
PMID- 11010404
TI - Expanding the role of the board.
PMID- 11010405
TI - Community benefits impact, Part 3.
PMID- 11010406
TI - Putting patients and families first.
PMID- 11010407
TI - Consumerism redefined ... the e-health imperative.
PMID- 11010408
TI - Customer-centered redesign: a requisite for creating effective improvements.
PMID- 11010409
TI - A stroll through the heart.
PMID- 11010410
TI - Managing investment risk through asset allocation.
PMID- 11010411
TI - Be an Internet millionaire and we may like you.
PMID- 11010412
TI - High tech, high touch.
PMID- 11010413
TI - Today's commitments required for tomorrow's success.
PMID- 11010414
TI - Tomorrow is today.
PMID- 11010416
TI - Champions of care.
PMID- 11010415
TI - The 2000 Ludwig Award winners: setting the pace for a new millennium.
PMID- 11010417
TI - Twenty-first century health care consumers.
PMID- 11010418
TI - Rethinking rehab in the "post-BBA" market.
PMID- 11010419
TI - Rethinking rehab: millennium market demands innovation, best practices, and
consumer focus.
PMID- 11010420
TI - Top 10 trends: rehab's "upside/downside potential" in the millennium.
PMID- 11010421
TI - MedPAC begins work on SNF PPS updates; urges changes to quality monitoring,
assessment tools.
PMID- 11010422
TI - Preliminary Abt research points to four possible refinements to RUGS-III; HCFA
proposal expected soon.
PMID- 11010423
TI - Thinking of bringing therapy in house? Heed these considerations first.
PMID- 11010424
TI - Underuse of beta-blockers in cardiovascular medicine.
PMID- 11010425
TI - Cardiodynamic effects and mechanisms of action of beta-blockers.
PMID- 11010427
TI - Dispelling the myth: incorporating beta-blockers into practice guidelines.
PMID- 11010428
TI - How to achieve QI cooperation from health system physicians.
PMID- 11010426
TI - The effect of beta-blockers on morbidity and mortality associated with heart
failure.
PMID- 11010429
TI - Big and small hospitals try benchmarking cooperative.
PMID- 11010430
TI - Small facility explores benchmarking options.
PMID- 11010432
TI - Inside Mecon's data mine: ground ambulance service.
PMID- 11010431
TI - New system protects staff from pathogens.
PMID- 11010433
TI - In tornado aftermath, Mitchell Country Hospital treats 200 people, scores 93 on
JCAHO inspection.
PMID- 11010434
TI - A case for rural hospitals: tornadoes may serve as wake-up call to state and
federal lawmakers, rural citizens.
PMID- 11010435
TI - Supreme Court says challenges to Medicare must initiate at HHS.
PMID- 11010436
TI - A picture of teamwork: as tornados rip through four south Georgia counties, six
hospitals rise to the occasion treating more than 120.
PMID- 11010437
TI - Online tools help agencies cope with PPS.
AB - A flurry of software development, much of it web-based, offers alternatives for
agencies to address PPS requirements, streamline operations, and improve agency
performance. PPS changes everything--dramatically altering the home care
community's financial incentives and focusing attention on technologies that will
enable agencies to succeed in this new environment.
PMID- 11010438
TI - Running the numbers--is going high-tech in your agency's best interest?
PMID- 11010439
TI - The Internet. Building knowledge & offering integrated solutions to health care.
AB - Technology is changing the way we do things, including how the health care
community provides information and services to the public. Disparate populations,
once separated by distance and time, will experience dramatic changes as they
become part of a global community. Fundamental changes will continue to occur in
the way health information is received, utilized, exchanged and stored. This
article explores access to the Internet as well as applications of interactive
health technology and the emerging issues surrounding technology use.
PMID- 11010440
TI - TeleHomeCare: connecting the home and the home care agency.
PMID- 11010441
TI - Medical devices in the home: present and future applications.
AB - Putting together a comprehensive telehealth program is similar to putting
together a puzzle. You have to fit all of the pieces together to see the big
picture. An important piece of that puzzle is medical devices for telemonitoring.
The equipment used in a telehealth program can span from low end, such as simply
using a telephone; to high end, in which two-way audio-video systems are used
with computer documentation, outcome software, and various medical device
options.
PMID- 11010442
TI - The new hospice compliance plan: defining and addressing risk areas. Part 3.
AB - The recently released OIG guidelines to ensure compliance with federal and state
statutes, rules, and regulations, and private-payor health care program
requirements provide a blueprint for developing such programs. This is the last
of three installments that focus specifically on the 28 risk areas identified in
the guidance and offer strategies for incorporating them in a hospice compliance
program. The authors have organized the 28 risk areas under 9 topic domains to
simplify the task of tackling the guidance. This article covers the areas of
nursing home care, marketing, and Conditions of Participation.
PMID- 11010443
TI - Partnering to prepare for success.
PMID- 11010444
TI - Exploring the new frontier: home care gets wired.
AB - The driving forces toward adoption of TeleCare into the non-acute care setting
are more compelling than ever before. The dramatic increase in our elderly
population, which provides an endless consumer base, availability of functional
and affordable technologies, and a national mandate to control costs of health
care are forcing even the most skeptical health care decisionmakers to accept
TeleCare as a standard model of care. Add to this the most severe nursing
shortage to date and the formula is complete.
PMID- 11010445
TI - Managed care liability today: laws, cases, theories, and current issues.
AB - Managed care entities face numerous liability issues in today's changing
healthcare environment. This Article provides the plaintiff with a comprehensive
road map for navigating the many avenues of managed care liability. The author
describes ERISA pre-emption provisions and suggests ways plaintiffs' attorneys
can strive to narrow the pre-emption. The Article also provides in-depth analysis
of each theory of managed care liability that has been litigated against managed
care entities to date, and then goes on to explore state laws imposing liability
on managed care entities, and how HMO liability is being reformed through
legislative action. For plaintiffs' attorneys seeking the full spectrum of
theories of managed care liability, or for defendants' attorneys wanting to
remain updated on all potential claims to defend, this Article constitutes an
extensive primer on the current issues.
PMID- 11010447
TI - Consumer managed care appeals: are the available procedural protections
fundamentally fair?
AB - Managed care incentives to reduce costs have also resulted in incentives to deny
care. Anecdotes concerning managed care denials of care have led to a consumer
outcry for protection either through the use of procedural due process or by the
establishment of patient rights that would include appeal and grievance
protections. This Article reviews the procedural protections of constitutional
due process, the Consumer Due Process Protocol, and the Patient Bill of Rights.
The Article then extensively discusses the availability of these procedural
protections in various public and private forums. The discussion of public forums
includes proposals contained in recent national legislative initiatives. The
author then reviews relevant federal and state law, as well as Uniform Law
proposals. Next, the Article analyzes the protections provided by accreditation
agencies, dispute resolution organizations, professional organizations, and
health insurers. Finally, the author recommends criteria to be used to determine
whether a procedure is fundamentally fair.
PMID- 11010448
TI - The National Practitioner Data Bank: coping with the uncertainties.
AB - The National Practitioner Data Bank is a database of adverse events involving
physicians and other practitioners. Querying the database is mandatory for
hospitals in several situations. So too, hospitals are required to report
specified adverse events. Thus, hospitals need to be able to identify incidents
that are reportable events, events that require them to update the databases, and
any possible liability issues that may surround the hospital's reporting duties.
The author argues that the regulations are unclear in addressing these issues.
Likewise, he notes that practitioners should be aware of other problems with the
reporting system, including the lack of sufficient Data Bank security.
PMID- 11010446
TI - Creating problems as part of the "solution": the JCAHO Sentinel Event Policy,
legal issues, and patient safety.
AB - The recently reported number of patient deaths attributable to medical errors is
staggering. In response to this crisis, the Joint Commission on Accreditation of
Healthcare Organizations ("JCAHO") proposed its Sentinel Event Policy. The policy
mandates self-reporting by hospitals accredited by the JCAHO. This Article argues
that the JCAHO's policy shows an inattention to the legal realities of discovery
and absence of immunity. Until the JCAHO addresses these issues, self-reporting
will have limited success. This Article suggests that to promote patient safety,
self-regulatory reports should go to a neutral, nonsanctioning third party, an
approach adopted from aviation's highly successful reporting system.
PMID- 11010449
TI - Managing the outpatient data grouping process.
PMID- 11010450
TI - Freestanding continuing care facility offers lessons in how to keep customers
happy.
PMID- 11010451
TI - McManis: technology, consumerism keys to a successful future U.S. health system.
PMID- 11010452
TI - Flurry of solicitous e-health businesses offers hospitals plenty of alternatives.
PMID- 11010453
TI - BBA pain gets worse, new studies show; pinch not likely to go away, EY consultant
says.
PMID- 11010455
TI - Telehealth expands unrealized dream.
PMID- 11010454
TI - Failure of AHERF offers plenty of lessons in how not to run an integrated health
system.
PMID- 11010456
TI - A visit to a Mexican specialty hospital: the patient as leader?
PMID- 11010457
TI - Looking for Dr. Jekyll but hiring Mr. Hyde: preventing negligent hiring,
supervision, retention, and training.
PMID- 11010458
TI - Misconceptions regarding restructuring of registered nurse positions in western
New York and southern Ontario.
PMID- 11010459
TI - Acquired immunodeficiency syndrome (AIDS) update, Part 2.
PMID- 11010460
TI - Economic development: a moral imperative for creating flourishing communities.
PMID- 11010462
TI - Price survey. Market forces squeeze stent prices.
PMID- 11010461
TI - Preventing needlestick injuries in healthcare settings.
PMID- 11010463
TI - E-commerce poses more questions than answers.
PMID- 11010464
TI - Transforming health services management education and development: a challenge
for the new millennium.
PMID- 11010465
TI - Evolving health services administration education: keeping pace with change.
AB - Virginia Commonwealth University (VCU) celebrated its golden anniversary in 1999.
It was an occasion for faculty and alumni to renew memories of their experiences
together and marvel at the dramatic changes they have seen in the health care
industry. This qualitative study was undertaken to reflect on the department's
immediate future course, and to learn how to reposition the education program and
curricula to respond to evolving industry needs and demands. Results and
conclusions are based on interviews conducted with several stake-holder groups,
including VCU alumni, who are executives in the health sector; human resources
recruitment officers; and selected program directors from leading health
administration (HA) education programs in the U.S. Trends are identified in the
health care industry environment, and strategies are proposed for the HA
education programs to strategically adapt for the future.
PMID- 11010466
TI - Perceived effectiveness of teaching methods for heath services administration
education.
AB - This article brings to the forefront the challenges of establishing an empirical
link between teaching methods and education outcomes in the classroom. In the
health administration education field, precious little empirical data exist on
the effectiveness of various teaching methods and approaches on achieving
education outcomes. Results are reported from the 1998 National Survey of program
directors of the AUPHA graduate programs on the perceived effectiveness of a wide
range of teaching methods, using a Likert scale, ranging from very effective to
not very effective. The authors elaborate on the highest- and lowest-ranked
teaching methods, and propose a research agenda for measuring education outcomes
in the classroom.
PMID- 11010467
TI - The role of accreditation in transforming health services management education.
AB - The core function of the Accrediting Commission on Education for Health Services
Administration (ACEHSA) is to improve quality in health services management
education. All specialized accrediting agencies provide quality assurance by
developing standards of quality, assessing programs and reporting to
stakeholders, as part of their public accountability function (Council for Higher
Education Accreditation). Standards of quality derive from the level of
competency considered essential within the domain of practice of health services
managers. Accreditation review by ACEHSA is oriented to quality improvement and
quality assurance, which have different purposes and are difficult to accomplish
in the same process. The purpose of this paper is to discuss ACEHSA's role in
evaluating the quality of health services management education programs in North
America. The first objective is to describe the process of defining quality and
to identify the skills, knowledge and abilities derived from it. The second
objective is to discuss the measurement of quality, including using standardized
measures, and determining whether the purpose is quality improvement or quality
assurance. The third objective is to examine how quality measures are reported,
and how reporting impacts the quality assessment process. Finally, the future
role of ACEHSA is discussed, with regard to benchmarking measures of quality and
publicly reporting relative levels of academic program quality.
PMID- 11010468
TI - A framework for evaluating the impact of health services management education.
AB - The objectives of this paper are three-fold. The first is to propose a conceptual
and analytical framework for planning and evaluating health services management
education programs. The framework was developed in response to the health care
industry restructuring and the emerging questions and concerns regarding how to
strategically redesign the educational programs for the twenty-first century.
Additionally, it was used to develop a questionnaire for the 1998 National Survey
of Program Directors. The second objective is to suggest variables for
operationalizing the framework as the field considers initiatives such as,
"Evidence-Based Health Administration Education" (AUPHA Education Outcomes Task
Force 1999; Griffith 2000) and other more standardized, quantifiable approaches
to assessing program quality. The third objective is to report selected results
from the 1998 National Survey of Program Directors focusing on the major changes
impacting the health services industry and the implications for management
education and development. In the future, ACEHSA and other accrediting
commissions will likely consider evidence-based evaluation criteria for assessing
and improving education program quality. The framework presented in this paper
can be used as a starting point for conceptualizing and developing valid and
reliable measures.
PMID- 11010469
TI - How location can make or break your practice.
PMID- 11010470
TI - I opened my home to a homeless patient.
PMID- 11010471
TI - Keep up with old friends--but don't treat them.
PMID- 11010472
TI - The new rules on informed consent.
PMID- 11010473
TI - Legislators begin their effort to curb medical errors.
PMID- 11010474
TI - The managed care program isn't working the way Congress intended.
PMID- 11010475
TI - Risk adjustment: Medicare's latest move to tinker with your income.
PMID- 11010476
TI - Make your office layout serve your needs.
PMID- 11010477
TI - The snake in the ER.
PMID- 11010478
TI - Attacking managed care with a full-court press.
PMID- 11010479
TI - Where students pledge themselves to primary care.
PMID- 11010480
TI - "Don't let go".
PMID- 11010481
TI - Thank you, Carlos, for rekindling my love of medicine.
PMID- 11010482
TI - Disabled by my illness and my insurer.
PMID- 11010483
TI - How to squash a small malpractice claim.
PMID- 11010484
TI - Why didn't I speak up for this patient?
PMID- 11010485
TI - A managed care sting.
PMID- 11010486
TI - Helping the homeless move ahead with their lives.
PMID- 11010487
TI - Offering medical advice on the Web.
PMID- 11010488
TI - Will the Internet finally put an end to paperwork?
PMID- 11010489
TI - How connectivity is changing practice.
PMID- 11010490
TI - Professional liability. 1998: a year when malpractice awards mushroomed.
PMID- 11010491
TI - They're still working on the electronic medical record.
PMID- 11010492
TI - Medicare's new red flag: same-day readmissions.
PMID- 11010493
TI - When to hire another doctor--and how to make it pay.
PMID- 11010494
TI - Find a doc, keep a doc, keep a doc happy.
PMID- 11010495
TI - How unhappy are women doctors?
PMID- 11010496
TI - How I almost killed Otis.
PMID- 11010497
TI - The biggest coding blunders--and how to avoid them.
PMID- 11010498
TI - Congress backs away from mandatory reporting of medical errors.
PMID- 11010499
TI - Managed care reform? Sure--but don't look to Washington.
PMID- 11010500
TI - How to harmonize with PAs and NPs.
PMID- 11010501
TI - Things to do in Denver when your practice is dead.
PMID- 11010502
TI - Get the most out of every patient visit.
PMID- 11010503
TI - Quality facility standards: more than the right thing to do.
PMID- 11010504
TI - Developing a Web site for your practice.
PMID- 11010505
TI - Dynamic modeling of outpatient systems to balance provider resources and patient
access.
AB - Improving patients' access to appointments remains a major goal for most managed
care organizations and group practices. A number of factors affect the length of
time a patient must wait to see a physician or other provider. This article
describes those factors and how dynamic modeling can assist decision makers in
determining the appropriate number of providers or changes in practice or
operations needed to meet given access targets.
PMID- 11010506
TI - Fixing responsibility for risk management.
AB - The responsibility for carrying financial risk for medical coverage has migrated
from individuals to insurers to employers to providers, without finding a
satisfactory home. Each shift further complicates the health care infrastructure,
as other responsibilities in the management of benefits and provision of care
gravitate to the stakeholder who accepts risk. The social imperative to broaden
coverage is forcing a change in the mechanisms of risk management--from avoiding
high-risk patients, to managing those patients to better outcomes. In this paper
we seek to identify objectively the most appropriate party to carry the financial
risk of medical coverage, consider what characteristics are necessary to make
that a practical and enduring solution, and examine the secondary effects of the
structure required to support that solution.
PMID- 11010507
TI - An academic practice's transition to the business of medicine in the community. A
case study.
AB - This case study highlights the problems confronting a clinical practice
corporation affiliated with a major medical school, and the business realizations
it made in the acquisition of a community-based clinic. Launching a financially
viable enterprise requires careful planning, determination of formal goals and
expectations, an appropriate mix of physicians and services, a specific marketing
campaign and community support.
PMID- 11010508
TI - When you suspect the healer needs healing.
AB - By recognizing the causes of stress among physicians in your office or hospital
and proactively addressing them, you can play a significant role in improving
patient care.
PMID- 11010509
TI - Ready: how to keep your customers coming back.
AB - Customer service is a major, but often overlooked, issue in health care today.
While other industries and organizations recognize how good customer relations
can affect long-term success, many health care providers have yet to learn this
valuable lesson. The Ritz-Carlton, which won the prestigious Baldridge Award for
service, has a well-earned reputation for excellent customer service. Like health
care providers, this hotel industry icon hires hourly workers, puts them in
uniform and has them work in teams. Unlike health care, however, The Ritz-Carlton
seems to be able to generate a much higher level of customer satisfaction. How?
This chapter illustrates the techniques the hotel chain uses to accomplish its
goal and how these important tools can apply to the health care industry.
PMID- 11010510
TI - Kaiser on track to recovery.
PMID- 11010511
TI - Top court toughens rules. Providers can't take Medicare grievances directly to
federal court.
PMID- 11010512
TI - St. Vincent's is one dumped in breakup.
PMID- 11010514
TI - Late, but online. Big group purchasing organizations play catchup in bid to place
services on Internet.
PMID- 11010513
TI - AHA backs bill to end key disparities.
PMID- 11010515
TI - More BBA relief not likely.
PMID- 11010516
TI - Settlements may not unbumdle. Appeal decision notwithstanding, hospitals unlikely
to get fully repaid in fraud probe.
PMID- 11010517
TI - Doc contracts under fire in Calif.
PMID- 11010518
TI - Worst-case scenario. Atlanta hospital's demise, despite powerful backing, makes
it poster child for industry woes. .
PMID- 11010519
TI - Ga. hospital barely stays afloat.
PMID- 11010520
TI - Taking a stand is easier in a crowd.
PMID- 11010521
TI - What hospitals 'see' they get. Private sector acquiesces to providers' price
hikes.
AB - With government reimbursement continuing to be the target for budgetary
squeezing, hospitals are turning to the only place where they can raise prices:
the private sector. There's mounting evidence that hospitals are exacting higher
rates from health plans and other nongovernmental payers, marking a resurgence of
cost-shifting following a five-year hiatus.
PMID- 11010522
TI - Providers put faith in Internet.
PMID- 11010523
TI - Care on the frontier. Alaska hospital meets challenges not found in 'lower 48'.
PMID- 11010524
TI - Patients get choices in drug pricing.
PMID- 11010525
TI - Aching backs a blooming business.
PMID- 11010526
TI - Credit crunch. Many healthcare companies are discovering a good lender is hard
to find.
PMID- 11010527
TI - Premier's feeling lucky.
PMID- 11010528
TI - La. providers challenge big Medicaid cuts.
PMID- 11010529
TI - 'Statistically insignificant' but critical. Increase in improper Medicare
payments weakens healthcare providers' case for BBA relief.
PMID- 11010530
TI - Ohio system plans expansion. Mount Carmel challenges OhioHealth in quest to be
state's largest system.
PMID- 11010531
TI - O'Leary clarifies the JCAHO's stance.
PMID- 11010532
TI - New leaders drive managed care. Sensitivity with a bulletproof attitude required.
AB - It's been a time of rapid-fire change in the managed-care industry--change that
has included high-profile turnover in the executive suites at many of the large
publicly held HMOs. Stepping into the top jobs has been a new generation of
leaders with skills and qualities unheard of in boardrooms just a decade ago. But
those skills will be tested as the industry continues to evolve.
PMID- 11010533
TI - Reports find error-reporting takes faith.
PMID- 11010534
TI - 2000 construction & design survey.
PMID- 11010535
TI - AHERF executives arrested. Pa. attorney general says three stole endowment funds.
PMID- 11010536
TI - Aetna will go it alone.
PMID- 11010537
TI - Heart palpitations. Development of cardiac specialty-care hospitals often leads
to bitter market feuds.
PMID- 11010538
TI - Growth but no margins.
PMID- 11010539
TI - Joint venture creates cancer center.
PMID- 11010540
TI - Healthcare agenda puzzles Congress.
PMID- 11010541
TI - Healthcare becoming a lot less local.
PMID- 11010542
TI - Heavyweight hospitals build strength from within. Columbia, Tenet concentrate on
core groups of hospitals.
PMID- 11010543
TI - Do-it-yourself purchasing.
PMID- 11010544
TI - Bankruptcies' ripple effects.
PMID- 11010545
TI - A new revenue source.
PMID- 11010546
TI - MedPAC blames private payers. .
PMID- 11010548
TI - AMA cancels accreditation program.
PMID- 11010547
TI - Vencor walloped for $1.3 billion.
PMID- 11010549
TI - Double indemnity.
PMID- 11010550
TI - Credentialing in a vacuum.
PMID- 11010551
TI - A 'bad news sells' strategy.
PMID- 11010552
TI - Betting for a no-show.
PMID- 11010553
TI - Drug-free in Seattle. Harborview Hospital takes on heroin.
PMID- 11010554
TI - Another bailout looming?
PMID- 11010555
TI - Fiscally challenged. Psychiatric industry's hope is in consolidation, focusing
services.
AB - Psychiatric hospitals are closing in droves. Last year alone, at least 75 were
shuttered, up sharply from the previous year. And psych hospitals collectively
lost $254 million in 1998. To reverse the sector's fortunes, providers are
focusing on consolidation and specialty services. "Mental health isn't
glamorous," says David Moulthrop (left), CEO of a Wisconsin psych hospital. "But
there is a future, though the pie has shrunk."
PMID- 11010557
TI - Still governing.
PMID- 11010556
TI - A leader who mixes quality, profitability.
PMID- 11010558
TI - Taking a hike.
PMID- 11010559
TI - Small businesses fight Fla. insurers.
PMID- 11010560
TI - Use of locum tenens grows.
PMID- 11010561
TI - Challenging the REITs. Real Estate Investment Trusts.
PMID- 11010562
TI - Little change likely after rating firms' merger.
PMID- 11010563
TI - The politics of health.
PMID- 11010564
TI - A comparison of the awareness and utilisation of postoperative health services
provided to women with breast cancer in public and private hospitals.
AB - Nurses at a metropolitan Cancer Care Centre (CCC) noted that women who have had
recent breast surgery for carcinoma had significantly different levels of
knowledge and use of support services depending upon public or private
hospitalisation. The public hospital participants were more aware of the range of
available services (mean = 3.6) compared to women from the private sector (mean =
2.6). In addition, the public hospital participants were more likely to access a
wider range of services post discharge (mean = 2.21) compared to the private
hospital women (mean = 0.85). A significant difference was found between younger
and older women's use of services.
PMID- 11010565
TI - Improving local services for women with breast cancer: interviews with general
practitioners in central Sydney.
AB - We conducted interviews with 85 randomly selected general practitioners (GPs) in
Central Sydney to examine patterns of referral of women with breast cancer,
satisfaction with local services, awareness of evidence-based guidelines and
suggestions for local support. Previous experience was the most frequently cited
factor influencing choice of specialist (n = 80, 94%) followed by personal
knowledge of the consultant's expertise (n = 72, 85%). Only one third of
respondents agreed women wanted to be more involved in choosing the specialist (n
= 28, 33%). Of 79 women recently diagnosed with breast cancer, the majority (96%)
had been referred to a male surgeon (n = 71, 96%). While only 35% of the GPs
rated the care received by women with breast cancer in local facilities as
'excellent', significantly fewer rated communication between GPs and specialists
as 'excellent' (35% v 19%, p < 0.01). Younger GPs were less likely to rate
communication as 'excellent' compared with GPs aged 55 years or older (p = 0.01).
Only 18% of GPs considered their patients as having been 'very well informed'
about their treatment choices. Younger GPs were more likely than older GPs to
recall all available breast cancer guidelines (p = 0.02). Significantly more GPs
(68%) requested seminars with experts than any other types of educational support
(p < 0.001). To improve outcomes for women with breast cancer, mechanisms to
support communication between GPs and specialists are recommended. Seminars for
GPs with experts who emphasize evidence-based guidelines should be funded and
evaluated, especially for impact in meeting the needs of older GPs.
PMID- 11010566
TI - An assessment of the needs of oncology outpatients for the development of allied
health services.
AB - This article presents the findings of a study that arose out of the desire by the
Allied Health Professionals (AHP) at the Mater Hospital, Brisbane, to better
understand the needs of their clients in order to be able to offer a more
effective and appropriate service. A questionnaire designed specifically to
explore the needs of patients and their families for AHP services was
administered to consecutive patients (n = 62) attending the Mater out-patient
oncology clinic during one month. The findings provide a wealth of practical
information for AHPs to use in planning for the effective utilisation of their
services, as well as fresh insights into a number of theoretical issues that need
further research.
PMID- 11010567
TI - Emergency medicine and "acute" general practice: comparing apples with oranges.
AB - Emergency Departments (EDs) operate at the interface between the inpatient and
ambulatory sectors of health care. Because of shared funding between the
Commonwealth and States for ambulatory care, there has been intense focus on the
ED patient population, and the potential to shift the locus of care for non
inpatients. One of the frequently cited models for the provision of after-hours
GP services is the Balmain General Practice Casualty (GPC). This paper analyses
the GPC model, looking in detail at casemix, clinical quality, waiting times and
cost-effectiveness. It is argued that the services provided and the casemix of
the patient population of GPC and EDs are distinctly different. Cost
effectiveness for GPC has not been objectively established. Health service
planning should recognise the distinct but complementary roles of general
practice and emergency medicine. Evaluation of alternative models of service
provision should critically examine the available evidence, and comparisons
should be based on a precise analysis of equivalent services.
PMID- 11010568
TI - Home phototherapy for neonatal jaundice--technology and teamwork meeting consumer
and service need.
AB - 32 babies with uncomplicated physiological jaundice received home phototherapy
from a hospital/community team in southern Brisbane. All babies showed acceptable
reductions in their serum bilirubin on home therapy, and none required hospital
re-admission for phototherapy. Their families were highly satisfied with the home
program, and recorded high levels of confidence in their therapeutic
responsibilities. Community providers were able to deliver a high quality 24-hour
service, integrated with appropriate neonatology support. The cost of delivering
the home program was significantly less than a comparable hospital stay.
PMID- 11010569
TI - Improving clinical indicators in acute admissions to the Department of Geriatric
Medicine, Royal Perth Hospital.
AB - Clinical indicators are an important component of quality assessment of clinical
services. We outline the strategies used in the department of Geriatric Medicine
at Royal Perth Hospital (RPH) to report on and improve the results. The clinical
indicator for assessment of cognitive function had improved from 19% in September
1998 to 64% in February 1999. The clinical indicator for assessment of physical
function has been maintained at 80%. There have been revisions to the definitions
of the clinical indicators for 1999. The current clinical indicators used in this
department can be modified for comparison nationwide amongst geriatric units.
PMID- 11010570
TI - Developing mental health rehabilitation services in a culturally appropriate
context: an action research project involving Arabic-speaking clients.
AB - The present study illustrates the efforts by a community mental health service to
restructure the Mental Health Rehabilitation Program to meet more adequately the
needs of the Arabic-speaking population. It was discovered that the principles of
mental health rehabilitation theory are inherently Anglo-Australian and not
suitable for the Arabic-speaking population. Action research methodology was used
as a tool to drive the changes necessary to implement effective mental health
rehabilitation across cultures. Two new culturally relevant programs were
developed, staff attitudes to rehabilitation were changed and assertive
strategies were introduced to alter clients' attitudes and perceptions about
mental health rehabilitation.
PMID- 11010571
TI - Nurse-managed analgesia for renal colic pain in the emergency department.
AB - A retrospective chart review was conducted of patients with acute renal colic for
the years 1993 and 1997, in order to compare analgesia ordering and
administration practices before and after implementation of a nurse-managed,
titrated intravenous (i.v.) narcotic policy. The study demonstrated a significant
and sustained change in analgesia administration practices away from the
intramuscular (i.m.) route in favour of the i.v. route. For renal colic, in 1993,
76% of patients received i.m. narcotic analgesia compared to 3% in 1997. In
contrast, i.v. narcotic (with or without adjuvant (NSAID) was used in 3% of the
patients in 1993 compared to 95% in 1997.
PMID- 11010572
TI - Improving the utilisation of bilingual counsellors within a public sector mental
health service.
AB - An urban, public sector Area Mental Health Program reviewed its own bilingual
counsellor program as part of an Area-wide quality improvement project, and found
that the counsellors' roles needed to be better defined; that mainstream staff
needed to have more access to their expertise as cultural consultants; and that
their function as an Area team, rather than as service based staff, needed to be
encouraged. The bilingual counsellors decided to take up this challenge, and with
the support of the Area Director of Mental Health, worked together to redefine
their roles.
PMID- 11010573
TI - Managed competition.
PMID- 11010574
TI - Independent life expectancy in New Zealand, 1996-97.
PMID- 11010575
TI - The performance of Australian DRGs.
AB - This paper reports the results of an evaluation study of the Australian National
Diagnosis Related Groups (AN-DRGs). The evaluation was based on statistical
rather than clinical criteria with the principal goal being to provide
information for the future development of the classification system. As well as
comparing versions 1.0 to 3.0 of AN-DRGs, the project included a comparison of
these systems with the most recent versions of the DRG systems from the United
States. Taking all the evaluation criteria together, Version 3.0 of AN-DRGs
performed best of all the systems except for the All Patient Refined (APR)-DRGs
with its much larger number of groups. However, the differences between all the
classifications were slight. Data of higher quality are needed if further
refinements of the AN-DRGs are to produce substantial improvements in
performance.
PMID- 11010576
TI - EquIP accreditation: feedback from a Sydney teaching hospital.
PMID- 11010577
TI - Taking health seriously: the senate inquiry into public hospitals.
PMID- 11010578
TI - Distributional impact of higher patient contributions to Australia's
Pharmaceutical Benefits Scheme.
AB - This paper uses NATSEM's Pharmaceutical Benefits Model to analyse the effects of
a hypothetical 25 per cent rise in patient contributions to prescribed medicines
under Australia's Pharmaceutical Benefits Scheme (PBS). The model, based on
microsimulation techniques, is able to provide a much broader range of outcomes
information, at a much greater level of detail, than is possible with traditional
methods. Higher patient contributions are analysed in terms of their impact on
the government to patient split in PBS costs, as well as the distribution of such
costs across age groups, family incomes, family types and 36 prescribed medicine
types. Also considered are changes in the shares of family disposable incomes
spent on prescribed drugs arising from the higher patient contributions.
PMID- 11010579
TI - High length-of-stay outliers under casemix funding of a remote rural community
with a high proportion of aboriginal patients.
AB - The diagnosis related groups (DRG) classification was designed primarily to
categorize patients of acute short-stay hospitals in urban areas. As one might
expect, many studies have shown it is a less effective predictor of the needs-
and consequently the costs of care--of remote and socio-economically
disadvantaged communities. One way of improving the equity of funding involves
separating the cases in each DRG into inlier and outlier episodes, and making
different resource allocations for each category. This paper summarises the
outlier payment model used by the Health Department of Western Australia, with
emphasis on high length of stay outliers. The model provides additional funds for
high length of stay outliers, but funding levels are deliberately set below the
actual estimated costs of care, on the assumption that some of the additional
costs are a consequence of poor care management. All high length of stay outlier
episodes in the East Pilbara Health Service in 1997-98 were examined. It was
found that the outliers were predominantly Aboriginal patients from remote
communities with higher than average needs for care as indicated by their greater
tendency to have multiple conditions requiring treatment. The age distribution of
high length of stay outliers was quite different from that found in most
Australian hospitals, in that there was a higher proportion of young children. It
is concluded that, although the ideas on which the funding model is based are
sound, revisions of detail need to be considered to reduce the risk that the
burden of cost containment will fall to a disproportionate degree on the most
disadvantaged groups of patients.
PMID- 11010580
TI - Implications of decreasing surgical lengths of stay.
AB - A recent study at the Prince of Wales Hospital (PoW) compared health outcomes and
user satisfaction for conventional clinical pathways with a shortened pathway
incorporating day of surgery admission (DOSA), early discharge and post acute
care domiciliary visits for two high volume, elective surgical procedures
(herniorrhaphy and laparoscopic cholecystectomy). This paper quantifies cost
differences between the control and intervention groups for nursing salaries and
wages, other ward costs, pathology and imaging. The study verified and measured
the lower resource use that accompanies a significant reduction in length of stay
(LOS). Costs of pre- and post-operative domiciliary visits were calculated and
offset against savings generated by the re-engineered clinical pathway. Average
costs per separation were at least $239 (herniorrhaphy) and $265 (laparoscopic
cholecystectomy) lower for those on the DOSA pathway with domiciliary post acute
care.
PMID- 11010581
TI - Clinical pathways: a direction forward in health care.
AB - As in many developed nations, health care consumers in Singapore are demanding
better (and more costly) services. At the operational level, one way to address
consumers' demands while ensuring cost-effectiveness is through the
implementation of a clinical pathway program. This paper provides an overview of
the program at Changi General Hospital (CGH), a regional general acute care
hospital in the Republic of Singapore. The paper highlights the problems
encountered during the planning, developing and implementing phases. It concludes
by predicting what the future might hold for clinical pathways in Singapore and
the South East Asian Region.
PMID- 11010582
TI - Clinical pathways involving general practice--a new approach to integrated health
care?
AB - The Mater Mothers' Hospital, South Brisbane recently identified a number of
difficulties with the maternity share-care program it runs with 1100 local GPs.
This paper describes an integration approach developed at the Mater which has
addressed these problems via the use of clinical management guidelines across the
whole episode of care, the provision of a patient held record/pathway as a
clinical practice prompt, clear communication and information management
protocols between hospital and general practice, and the provision of continuing
medical education for share-care practitioners.
PMID- 11010583
TI - WESTCOP: a disease management approach to coronary artery disease.
AB - Disease management is a systematic approach to improving care of populations of
patients with specific clinical conditions. Critical to success are the formation
of collaborative teams of health care stakeholders, development and promulgation
of clinical practice guidelines, and performance measurement and feedback to
providers as a process of continuous practice improvement. This article describes
a disease management program for patients with coronary artery disease in a
provincial health district with a population of 180,000. It discusses the
rationale and methods behind the operationalisation of the main program elements,
benefits achieved to date and challenges confronted.
PMID- 11010584
TI - Use of monoclonal fluorescent antibodies for the detection of B. pertussis and B.
parapertussis.
AB - While it has been said that PCR is likely to replace DFA as the test of choice,
accessibility to and cost of the technique may limit the number of laboratories
that are able to implement the process. Still, the advantage of DFA staining
relative to other diagnostic methods, including PCR, is the provision of a rapid
result and lower overall cost. The laboratory diagnosis of pertussis remains
problematic, and polyclonal DFA reagents for its detection have brought into
question the utility of DFA. However, the integration of a commercially available
monoclonal DFA reagent, in combination with the development and standardization
of existing procedures, should provide clinicians with an improved method for the
diagnosis and epidemiology of pertussis.
PMID- 11010585
TI - Laboratory support in a regional approach to joint purchasing and materials
management.
PMID- 11010586
TI - Evaluation of a Troponin I assay employing enhanced chemiluminescence technology.
PMID- 11010587
TI - Rapid identification of Haemophilus and other bacteria by matrix-assisted laser
desorption ionization time-of-flight mass spectrometry.
PMID- 11010588
TI - Deconstructing disease: a pathologist's perspective.
PMID- 11010589
TI - Cost-effective liquid-fixed cytology specimen processing with an economical
cytocentrifuge.
PMID- 11010590
TI - Comparison of metal ions in biological samples of schizophrenic patients and
control subjects.
PMID- 11010591
TI - Polystyrene microsphere spray standards based on CFC-free inhaler technology.
AB - Metered pressurized sprays were formulated containing polystyrene microspheres
(PSM) suspended in 5% w/w ethanol in 1,1,1,2-tetrafluoroethane (HFA 134a).
Suspensions with defined number concentrations, packaged in pressure-resistant
glass containers, and fitted with specified 50-microL metering values and
actuators were sonicated and fired (as if they were metered dose inhalers or
MDIs). Following propellant evaporation, PSM dispersions in air containing > 98%
singlets resulted from actuation of 3, 5, and 8 microns PSM suspensions
containing 0.00125% w/w 3 microns, 0.05% w/w 5 microns or 0.3% w/w 8 microns
PSMs, respectively. Spray characteristics from these systems depended on PSM
concentration, PSM size, PSM source, and actuator dimensions. Adhesion of
suspended PSMs to the internal glass surfaces of the containers were easily
reversed by sonication but not prevented by a wide range of surfactants. Over a
period of 6 months storage, these formulations produced reproducible PSM aerosols
with known aerodynamic properties useful for calibration purposes.
PMID- 11010592
TI - Aerosol morphometry and aerosol bolus dispersion in patients with CT-determined
combined pulmonary emphysema and lung fibrosis.
AB - The simultaneous occurrence of pulmonary fibrosis and emphysema may present
considerable problems in clinical assessment. Recent studies have shown that
Aerosol Derived Airway Morphometry (ADAM) and Aerosol Bolus Dispersion (ABD) are
changed in patients with pulmonary emphysema. This study was performed to assess
the effect of simultaneous lung fibrosis in patients with emphysema on ADAM and
ABD. ADAM and ABD measurements were performed in 20 patients with lone high
resolution CT scan (HRCT) confirmed emphysema (E), and compared to those in 15
emphysematics with HRCT-confirmed superimposed pulmonary fibrosis (FE). In both
groups the peripheral effective airspace dimension (EAD) (E: 0.63 +/- 0.20 mm;
FE: 0.60 +/- 0.27 mm, N.S.) was increased by more than a factor of two compared
to that of healthy subjects (0.28 +/- 0.05 mm) (p < 0.001). Patients with E
showed a significantly higher bolus dispersion than patients with FE (724 +/- 122
cm3 vs. 546 +/- 80 cm3; p < 0.001). However, in patients with FE, bolus
dispersion was still significantly higher than in previously published control
groups of healthy subjects (546 +/- 80 cm3 vs. 455 +/- 68 cm3; p < 0.001). The
results of this study confirm that ADAM and ABD are powerful tools for
identifying emphysema even in patients with superimposed pulmonary fibrosis.
PMID- 11010593
TI - Characterization of the laryngeal jet using phase Doppler interferometry.
AB - The purpose of this study was to characterize the effects of the laryngeal jet on
inhalation air flows in the trachea, and to extend these ideas to further an
understanding of aerosol deposition in this region. Phase Doppler Interferometry
was used to characterize axial velocity and turbulence intensity contours in the
tracheal section of a cadaver-based larynx-trachea model. An array of 30
measurements was made at each of 6 downstream planes within the tracheal portion
of the model (immediately downstream of the larynx, and at 0.5, 1, 2, 3, and 4
diameters further downstream). The flow was characterized for steady state flow
at three Reynolds numbers (1250, 1700, and 2800). The Re = 1250 case approximates
the inhalation of a 6-year-old child. Reverse flows with significant velocities
were noted in the anterior trachea within one diameter downstream of the larynx,
for all three flow cases. The cross sectional area of the reverse flow regions
was larger for the lower Reynolds number cases. These reverse flows are a
consequence of the nearly triangular shape of the lumen between the vocal folds
in the larynx and constitute a potential deposition mechanism. High levels of
axial turbulence intensity were noted near the anterior/left tracheal walls
within one diameter downstream of the larynx. This indicates the potential for
deposition due to turbulence in this region. Turbulence levels were still
significant after four downstream diameters, indicating the potential for
turbulent deposition at positions further downstream, including the bronchial
tree where passage diameters are smaller. Contrary to expectations, turbulence
levels were approximately 20% higher for the Re = 1250 case compared to the Re =
2800 at the furthest downstream locations (with 99% confidence). This is likely
due to the complex nature of the confined jet flow.
PMID- 11010594
TI - Validation of a new breathing simulator generating and measuring inhaled aerosol
with adult breathing patterns.
AB - The use of breathing simulators for the in vitro determination of the inhaled
mass of drug from nebulizers has become widely accepted. Their use is, however,
based on the assumption that there is a correlation between the in vitro and in
vivo inhaled mass of drug. The aim of the study was therefore to investigate
whether a new breathing simulator--the MIMIC Breathing Emulator (Medic-Aid
Limited, Bognor Regis, UK)--could accurately emulate the in vivo inhaled mass of
budesonide suspension for nebulization. Eight adult healthy subjects were
included. Each subject inhaled for 2 min from a Spira Module 1 jet nebulizer
(Respiratory Care Center, Hameenlinna, Finland), charged with 1.0 mg of
budesonide suspension for nebulization (0.5 mg mL-1, 2 mL suspension,
AstraZeneca, Sweden) and supplied with an inhaled mass filter between the
nebulizer and the subject. The breathing patterns were recorded during the
nebulization and simulated in vitro at two different experimental sites
(simulations A and B) with the breathing simulator. With the patients breathing
through the filters (in vivo test), inhaled mass of budesonide averaged 103.6
micrograms. The two in vitro experiments using the simulator revealed similar
results with in vitro simulation A equal to 101.0 micrograms and simulation B
99.1 micrograms. There were no statistically significant differences between the
in vivo results and those of in vitro simulation A. Results were significantly
different for simulation B (p = 0.032) although the difference was less than
4.5%. These data indicate that the breathing simulator can be used to accurately
simulate sine waveforms, human breathing patterns, and the in vitro and in vivo
inhaled mass of budesonide suspension for nebulization.
PMID- 11010595
TI - The choice of compressor effects the aerosol parameters and the delivery of
tobramycin from a single model nebulizer.
AB - Recent U.S. Phase III trials of the aerosolized delivery of tobramycin to cystic
fibrosis (CF) patients demonstrated a significant improvement in pulmonary
function and in sputum bacterial density. These trials used the Pari LC Plus
nebulizer and DeVilbiss Pulmo-Aide compressor. This compressor is not generally
available in Europe, and its power requirements do not match the European power
supply. Thus alternate compressors were evaluated, using the LC Plus nebulizer,
in preparation for European clinical trials. Aerosol particle size distribution,
nebulization time (min), and the respirable dose of tobramycin (mg within 1-5 mu)
were obtained for seven compressor models. The respirable quantity delivered by
each of the European compressors (240 Volts, 50 Hz) was compared to the LC Plus
and PulmoAide compressor (120 Volts, at 60 Hz). The U.S. system delivered 71.4 mg
of the 300 mg instilled dose within the respirable range; using the European
compressors, between 63.0 and 74.8 mg was delivered. With a 97% confidence that
the delivered tobramycin was within 20% of the standard, we conclude that the
SystAm 23ST, MedicAid CR50 and CR60, Pari Master and the Pari Boy compressors are
equivalent to the U.S. standard; the Hercules and the SystAm 26ST compressors
were not statistically equivalent to the standard. Using the LC Plus nebulizer,
five European compressors delivered doses of TOBI that are similar to the doses
delivered by the DeVilbiss PulmoAide compressors, and thus may be expected to
produce clinical results similar to those of the U.S. trials.
PMID- 11010596
TI - Comparing HFA MDI aerosol delivery in spacers.
PMID- 11010597
TI - Regional mucociliary clearance in patients with cystic fibrosis.
AB - This paper reports on a large retrospective analysis of mucociliary clearance
(MCC) studies in a group of 59 patients with cystic fibrosis (CF) and 17 age
matched healthy subjects. As many of the CF patients were studied on multiple
occasions, a total of 184 patient studies are presented. MCC was measured using a
radioaerosol and gamma camera technique. In addition to whole lung clearance, MCC
was measured from the central, intermediate, peripheral, basal, mid and apical
regions of the lung. MCC was markedly decreased in the CF patient group. Not only
was whole lung clearance (14.2 +/- 1.4% vs. 28.0 +/- 3.7%) impaired, but also
clearance from the central (19.1 +/- 1.9% vs. 35.6 +/- 4.3%), intermediate (10.7
+/- 1.6% vs. 25.5 +/- 3.7%), apical (12.4 +/- 2.6% vs. 31.6 +/- 4.6%) and mid
(14.0 +/- 1.9% vs. 30.4 +/- 4.0%) regions. Attempts were made to identify factors
that may have influenced MCC in both the normal subjects and CF patients. Age,
gender, body mass index, patient genotype, penetration index, spontaneous cough,
and various lung function parameters were entered into a stepwise multiple
regression model, but none of the factors proved to be statistically important in
determining MCC. Both intrasubject repeatability and intersubject variability
estimates are presented for the patients and normal subjects that had multiple
studies. The values were found to be remarkably similar for both CF patients and
normal subjects and for both intra- and intersubject repeatability. With marked
deviation from normal ranges and good repeatability, the measurement of MCC in CF
patients would seem to be a valuable outcome measure for clinical trials
involving new pharmaceuticals and physical therapy designed to improve removal of
secretions from the airways.
PMID- 11010598
TI - Effects of dextran sulfate on tracheal mucociliary velocity in dogs.
AB - We have shown that low molecular weight dextran, as a potential mucolytic agent,
reduced the viscoelasticity and spinnability of cystic fibrosis (CF) sputum and
improved its ciliary transportability in vitro; it also reduced viscoelasticity
of healthy dog mucus in in vitro testing. In anesthetized dogs, dextran
administered by aerosol at 65 mg/mL increased tracheal mucus velocity, but this
increase was not sustained for higher concentrations. The purpose of the present
study is to evaluate whether low mol. wt. dextran sulfate, a charged
oligosaccharide, exhibits similar effects to previously tested neutral dextran
when administered by aerosol to anesthetized dogs in terms of mucus rheology and
mucociliary clearance rate. Healthy mongrel dogs were anesthetized with
pentobarbital and intubated. Aerosols of Ringer's solution or dextran sulfate
(m.w. 5000) dissolved in Ringer's were generated by Pari LC STAR nebulizer, and
delivered during 30-min periods of spontaneous breathing. Tracheal
transepithelial potential difference (PD, using agar filled electrodes) and
tracheal mucociliary velocity (TMV, by charcoal marker particle transport) were
measured under bronchoscopic control, and mucus for viscoelasticity analysis by
magnetic rheometry was collected by the endotracheal tube method. We performed
experiments in seven dogs, involving 30-min administrations of aerosol, separated
by 30-min periods of no aerosol. All dogs received inhalations of 6.5 mg/mL, 20
mg/mL, and 65 mg/mL dextran sulfate. Tracheal mucus viscoelasticity (average log
G* over 1-100 rad/s) decreased progressively with increasing dose of dextran
sulfate; for the highest concentration (65 mg/mL), log G* decreased by a factor
of 2.61 (p = 0.021). A modest increase in the TMV was observed for the first dose
of dextran sulfate (128% of baseline at 6.5 mg/mL, p = 0.066); thereafter TMV was
stable. PD increased significantly at each concentration of dextran sulfate
compared with Ringer control; however, there was no additional change between the
three groups. The solids content of collected airway fluid (%SC) was gradually
increased during successive 30-min dextran sulfate aerosols, indicating a
significant residence time for the dextran in the mucus, and correlating with the
decrease in viscoelasticity. These results suggest that dextran sulfate may be
potentially of therapeutic value as a mucolytic agent, assisting mucus clearance
by cough and physiotherapy, although whether it stimulates mucociliary clearance
remains to be proven.
PMID- 11010599
TI - Pulmonary drug delivery from the Taifun dry powder inhaler is relatively
independent of the patient's inspiratory effort.
AB - The Taifun dry powder inhaler (Leiras OY, Turku, Finland) is a breath-actuated,
multidose device, each metered dose containing 200 micrograms of budesonide. A
two-way randomized crossover gamma scintigraphic study was performed in 10
asthmatic patients to determine the in vivo deposition pattern of budesonide
inhaled from the Taifun. In vitro radiolabelling validation studies demonstrated
that the radiolabel could be used as an accurate marker to assess in vivo drug
deposition. Patients used either maximal inspiratory effort (targeted peak
inhalation flow 30 L/min) or submaximal inspiratory effort (targeted peak
inhalation flow 15 L/min) on each study day. Mean (S.D.) whole lung deposition (%
of metered dose) was 34.3 (5.8)% and 29.6 (5.9)% for the two inhalation flows.
The intersubject coefficient of variation in lung deposition was less than 20% on
both study days. Drug was deposited uniformly across the central, intermediate,
and peripheral lung regions for maximal and submaximal inspiratory efforts. The
study suggests that the Taifun is a superior drug delivery device compared with
many other inhalers, in terms of the amount of drug deposited in the lungs, the
reproducibility of the lung dose, and the relative flow--independence of lung
deposition.
PMID- 11010600
TI - Introduction to the pharmacoeconomics of herbal medicines.
AB - This article explores the need to perform pharmacoeconomic evaluations of herbal
medicines and assesses the extent to which this approach has been applied so far
to these products. There seems to be no compelling need for pharmacoeconomic
analyses of herbal over-the-counter medicines, but such analyses are certainly
warranted for herbal prescription medicines that have a high level of
reimbursement. Such preparations are used in Germany, in particular, where
physicians prescribed ginkgo, hawthorn, St John's wort, horse-chestnut and saw
palmetto to a value of more than DM50 million each in 1996. In our survey, only a
single pharmacoeconomic study, of uncertain quality, was found on these 5 herbs,
whereas several pharmacoeconomic reports on synthetic competitors were retrieved.
The time has come to submit highly reimbursed herbal prescription medicines to
the same rigorous pharmacoeconomic evaluations as their synthetic competitors. At
present, such studies are particularly important for Germany, but in the future
they may also become relevant for other countries, inside as well as outside
Europe.
PMID- 11010601
TI - Social phobia. Epidemiology and cost of illness.
AB - Social phobia is a prevalent and debilitating psychiatric disorder. It entails
significant economic costs in the form of educational underachievement, increased
financial dependency, decreased work productivity, social impairment and poorer
quality of life. It is associated with increased prevalence of other psychiatric
disorders including depression and alcohol dependence. Its onset is early and
typically precedes onset of comorbid disorders. Despite its debilitating effects,
social phobia is often unrecognised and is undertreated. The availability of
efficacious pharmacological and psychotherapeutic treatments for social phobia
makes it imperative to carefully consider the impact of this disorder and to
consider the cost effectiveness of available treatments.
PMID- 11010602
TI - A review of alternative approaches to healthcare resource allocation.
AB - The resources available for healthcare are limited compared with demand, if not
need, and all healthcare systems, regardless of their financing and organisation,
employ mechanisms to ration or prioritise finite healthcare resources. This paper
reviews alternative approaches that can be used to allocate healthcare resources.
It discusses the problems encountered when allocating healthcare resources
according to free market principles. It then proceeds to discuss the advantages
and disadvantages of alternative resource allocation approaches that can be
applied to public health systems. These include: (i) approaches based on the
concept of meeting the needs of the population to maximising its capacity to
benefit from interventions; (ii) economic approaches that identify the most
efficient allocation of resources with the view of maximising health benefits or
other measures of social welfare; (iii) approaches that seek to ration healthcare
by age; and (iv) approaches that resolve resource allocation disputes through
debate and bargaining. At present, there appears to be no consensus about the
relative importance of the potentially conflicting principles that can be used to
guide resource allocation decisions. It is concluded that whatever shape
tomorrow's health service takes, the requirement to make equitable and efficient
use of finite healthcare resources will remain.
PMID- 11010603
TI - Long-term treatment of multiple sclerosis with interferon-beta may be cost
effective.
AB - Multiple sclerosis (MS) is a devastating disease that can occur in early life,
progressing to rapid disability and loss of physical, psychosocial and economic
functioning, significantly affecting quality of life. The traditional treatment
for MS has been symptomatic, treating acute relapses without affecting the
underlying disease. The introduction of interferon-beta (IFN beta) has offered
significant clinical benefits by reducing the frequency of relapses and slowing
disease progression. Although the costs of this treatment are high, the costs to
society of caring for a patient disabled by MS are greater, and if IFN beta can
delay disease progression in the longer term, the economic impact would be
substantial. Previous pharmacoeconomic studies of IFN beta have suggested that
benefits can only be achieved at extremely high cost, with reported cost
effectiveness measures of up to 1 million pounds sterling (Pound) per quality
adjusted life year (QALY) [1995 values]. However, these studies have considered
only the short term benefits of IFN beta treatment: over 2 to 3 years, the impact
of treatment on patients' quality of life is relatively small, and cost-utility
analyses that do not consider longer term benefits nor include societal costs may
be misleading. The model reported here is based on the hypothesis that the delay
in disease progression seen in short term clinical trials is likely to continue
if treatment is continued. The model also assumes that the delay in disease
progression, which represents a reduction in brain atrophy, will result in
lasting clinical benefits even if treatment is stopped. These assumptions are
strongly supported by clinical trial data and the treatment hypothesis itself. A
delay in disease progression will result in a significant improvement in
functioning and quality of life, and if the costs associated with increased
disability can be postponed, even long term treatment of MS with IFN beta can be
shown to be cost effective. Using resource utilisation costs derived from an
economic evaluation of MS in the UK, it was possible to calculate the impact of
delaying disease progression in terms of both health service and societal costs.
An estimate of mean disease progression in patients with MS treated with IFN beta
1a compared with patients who did not receive disease-modifying agents suggested
that significant cost savings would be realised after about 12 years' treatment
with IFN beta-1a. The application of utility scores to the disease progression
curves also facilitated estimates of cost effectiveness, with cost per QALY
values ranging from 27,036 Pounds after 2 years' treatment with IFN beta-1a to
37,845 Pounds after 20 years' treatment (1995 values).
PMID- 11010604
TI - Using economic evaluations to make formulary coverage decisions. So much for
guidelines.
AB - BACKGROUND: It is mandatory for drug manufacturers requesting formulary inclusion
under the British Columbia (BC) provincial drug plan to submit a pharmacoeconomic
analysis according to published guidelines. These submissions are reviewed by the
Pharmacoeconomic Initiative (PI) of BC. OBJECTIVE: To assess the compliance of
submitted studies with specific criteria outlined in the guidelines, to assess
the methodological quality of individual submissions, and to demonstrate the
importance of submitting guidelines-compliant pharmacoeconomic analyses. DATA AND
METHODS: All submissions between January 1996 and April 1999 assessed by the PI
of BC were included. Submissions were reviewed according to a checklist to
establish compliance with respect to choice of comparator drug, study
perspective, sensitivity analysis, analytical horizon and discounting.
Submissions were examined for association between analytical technique and
author, and between source of submission and compliance. Association between
compliance and recommendation for approval was also examined. RESULTS: 95
applications were reviewed. Seven submitted no analyses. There were 25 cost
comparison/consequence, 14 cost-effectiveness, 11 cost-minimisation, 9 cost
utility/benefit and 29 budget-impact analyses. 65 of these 88 submissions failed
to comply with guidelines. Of these, 45% used an inappropriate comparator drug,
61% lacked a sensitivity analysis, 73% used a third-party payer and excluded a
societal perspective, 66% did not provide a long term evaluation and 25% did not
specify any time horizon. 80% of noncompliant studies were cost
comparison/consequence or budget-impact analyses (p < 0.001, Fisher's Exact). Of
25 cost-comparison/consequence and 29 budget-impact analyses, 19 (76%) and 24
(83%), respectively, were industry-conducted, whereas cost-effectiveness (11 of
14) and cost-utility/benefit (6 of 9) analyses were mostly subcontracted to
private consultants or academics (p < 0.001, Fisher's Exact). 74% of all
submissions (compliant and noncompliant) were not recommended by the PI for
listing as a provincial drug plan benefit, 16% received approval for restricted
benefit and 9% were recommended as full benefit. 80% of the noncompliant
submissions were not recommended (p = 0.06, Fisher's Exact test). Moreover, a
strong association between type of analysis and type of recommendation was found
(p = 0.03, Fisher's Exact test). Cost-comparison/consequence and budget-impact
analyses were less likely to be recommended. IMPLICATIONS OF FINDINGS: Our
findings show poor compliance with guidelines, especially among industry
conducted studies. Possible explanations are lack of expertise in
pharmacoeconomics and/or scepticism regarding the importance of guidelines and
submission quality in decision making. As corroborated by the strong associations
between type of recommendation and compliance, and between type of recommendation
and type of analysis, these 2 characteristics have a significant impact on
decision making.
PMID- 11010605
TI - Health-related quality of life in asymptomatic patients with HIV. Evaluation of
the SF-36 health survey in Italian patients.
AB - OBJECTIVE: To investigate the psychometric performance and clinical validity of
the 36-Item Short Form (SF-36) health survey when completed by asymptomatic HIV
positive Italian patients and to compare their health profile with a
representative sample of 2031 Italian citizens (the Italian norm). PATIENTS AND
METHODS: This was an observational, multicentre, cross-sectional survey.
Microbiologists throughout Italy recruited asymptomatic HIV-positive individuals
who were aged at least 18 years and aware of their infection. Investigators
collected demographic, social, clinical and treatment data. Patients, classified
into 2 clinical categories (A1 and A2) according to explicit pre-defined
criteria, completed the SF-36 health survey in the context of a medical visit.
RESULTS: Between April and July 1996, 46 microbiologists recruited 214 patients
(201 evaluable). No inconsistent responses were observed in 96% of the sample.
The usually recommended psychometric standards were satisfied, and the internal
consistency reliability indices were always greater than 0.70. Weak to moderate
associations were found between SF-36 health survey scores and physicians'
estimates of patients' physical performance, while no significant associations
were found with CD4+ counts. On average, HIV-positive patients reported lower
scores than the Italian norm, and patients in category A2 showed lower scores
than patients in A1. These differences were more relevant in scales describing
role limitations, general health perception, and psychological well-being.
CONCLUSION: Our study showed that the SF-36 health survey maintained its
psychometric properties in a sample of Italian asymptomatic HIV-positive patients
and produced data that showed its validity and robustness in such a setting.
PMID- 11010606
TI - The impact of pituitary adenoma on morbidity. Increased sick leave and disability
retirement in a cross-sectional analysis of Swedish national data.
AB - OBJECTIVE: To quantify sick leave and medical retirement for the year 1989 in
adults with a history of nonsecreting pituitary adenoma. DESIGN AND SETTING: A
cross-sectional analysis of official Swedish data from 1989 was performed. Sick
leave and disability pension data for these patients were obtained from the
Swedish National Social Insurance Board, which also supplied information on sick
leave taken by an age- and gender-matched control population of 5121 individuals.
Uptake of disability pensions and the reasons for drawing these pensions in the
study group were compared with national statistics. STUDY POPULATION: A group of
809 eligible adults with nonsecreting pituitary adenoma was identified from the
national cancer registry. MAIN OUTCOME MEASURES AND RESULTS: Almost a quarter of
the patients with a history of pituitary adenoma had retired due to ill health
(23.8%); this was twice the figure expected from national statistics (11.5%).
Similar results were obtained when men and women were considered separately. Some
patients (17%) had received disability pensions before the diagnosis of pituitary
adenoma, but the majority (75%) retired on medical grounds at least 1 year after
their diagnosis. The reasons for early retirement in the study group were largely
related to the diagnosis of pituitary adenoma (e.g. neoplasm, endocrine
disorders), but there was some evidence of an increase in the number of
disability pensions awarded because of diseases of the nervous system and sensory
organs. Patients with a history of pituitary adenoma took significantly more sick
leave in 1989 than those in the control group (mean 40.2 vs 24.0 days), and this
significant difference applied to both sexes. CONCLUSIONS: A cross-sectional
analysis of Swedish national data from 1989 showed excess morbidity, relative to
reference data, in patients with a history of nonsecreting pituitary adenoma.
Suboptimal conventional hormone replacement therapy and untreated growth hormone
deficiency might to some extent explain the increased morbidity found in the
present study.
PMID- 11010607
TI - Economic evaluation of enoxaparin sodium versus heparin in unstable angina. A
French sub-study of the ESSENCE trial.
AB - OBJECTIVES: To perform an evaluation from the societal perspective of the cost of
treatment with enoxaparin sodium versus unfractionated heparin (UFH) in patients
with unstable angina and non-Q wave myocardial infarction in France. DESIGN: Four
complementary cost-minimisation analyses based on the results of the Efficacy and
Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events (ESSENCE)
international trial were conducted. We assessed differences in medical resource
consumption and in duration of hospital stay in the whole study population (n =
3171) and for the French patients (n = 133). RESULTS: Results were consistent for
the study group as a whole and for the French subgroup. Among patients treated
with enoxaparin sodium, there was a statistically significant reduction in the
use of angiography and percutaneous transluminal coronary angioplasty (whole
group study: p = 0.024 and 0.006, respectively) and a trend towards shorter
lengths of hospital stay. The differences in angiography and angioplasty rates
led to estimated average net cost savings with enoxaparin sodium of French Francs
(FF)1555 per treated patient (whole study population) and FF9993 (French
subgroup) [1996 values]. The analyses based on the duration of hospital stay
resulted in estimated net cost savings with enoxaparin sodium of between FF1014
per treated patient (whole study population) and FF2804 (French subgroup).
CONCLUSION: Our study confirmed earlier results which show that enoxaparin sodium
is cost saving in the treatment of unstable angina.
PMID- 11010609
TI - Is universal coverage the American way?
PMID- 11010608
TI - Economic issues in the prevention of vertical transmission of HIV.
AB - In the absence of interventions, 20% of infants born to women infected with HIV
acquire infection from their mother at or before delivery. A further 15% are
infected through breast feeding. Prenatal testing for HIV allows infected women
to be reliably identified so that they can receive antiretroviral therapy and, in
countries with safe water supplies, be advised not to breast feed. These and
other interventions can reduce the risk of transmission to 5% or less. Economic
evaluations of prenatal testing for HIV are reviewed and compared in this
article, and future research priorities outlined. These studies set the costs of
testing and intervention against the averted lifetime costs of paediatric
infection, and generate estimates of the HIV prevalence threshold above which
there would be a net cost saving, or calculate the cost per life-year saved given
a particular prevalence. In the developed world, prenatal testing has been
adopted in many countries, and recent economic analyses broadly support this.
Future research is likely to focus on the incremental benefits of different
antiretroviral regimens in lowering transmission rates still further, with or
without elective caesarean section, and the possibility that some may lead to
adverse effects in uninfected infants exposed to them in utero. Some earlier
assessments in resource-poor settings concluded that prenatal testing was
unaffordable or of doubtful cost effectiveness. This negative conclusion appears
to be the result of very low estimates of the lifetime costs of paediatric HIV
infection, together with developed world conceptions of pre-test counselling. The
demonstration that nevirapine reduces transmission risk at a low cost has
transformed the outlook, and there is hope that antiretrovirals can act
prophylactically to prevent infection of the breast-fed child. However, to
achieve a sustained reduction in vertical transmission there may be a need to
evaluate the need for a strengthened infrastructure to deliver prenatal HIV
testing and treatment, as well as programmes to reduce HIV incidence in adults.
PMID- 11010611
TI - 'Problem patients': a fresh look at an old vexation.
PMID- 11010610
TI - Finding success in a capitated environment.
PMID- 11010612
TI - High-volume practice: are there trade-offs?
PMID- 11010613
TI - Understanding confidentiality and nonsolicitation clauses.
PMID- 11010614
TI - Local innovations provide managed care for the uninsured.
AB - A number of communities in the United States are adopting a managed care approach
to caring for low-income uninsured individuals. This Issue Brief focuses on such
programs in five of the 12 communities that the Center for Studying Health System
Change (HSC) is tracking intensively. It describes the local market factors that
motivated the creation and varying design of these initiatives, all of which seek
to increase access to primary and preventive care while managing the use of more
costly inpatient and emergency care. The Issue Brief also discusses the long
term viability of these programs as they attempt to simultaneously expand access
to services and contain costs for this growing population.
PMID- 11010615
TI - Who has a choice of health plans?
AB - Policy makers are concerned that consumers have no voice in the changing health
care system. They debate, however, whether the consumers' voice should be heard
through regulation, such as patient protections, or the marketplace. For market
forces to work in the consumers' interest, consumers must have a choice of plans
and detailed information on which to base their choice. New survey data from the
Center for Studying Health System Change (HSC) suggest that more consumers have a
choice of plans than is generally believed, and that the proportion of consumers
who have plan choice is increasing. According to HSC's 1998-1999 Household
Survey, 64 percent of families have a choice of health plans--two percentage
points higher than two years ago.
PMID- 11010616
TI - Improving quality and preventing error in medical practice.
PMID- 11010617
TI - Selecting a range of options.
PMID- 11010618
TI - Laparoscopic Nissen fundoplication.
PMID- 11010619
TI - Rheumatology.
PMID- 11010620
TI - Dispelling the myths and stigma of mental illness: the Surgeon General's report
on mental health.
PMID- 11010621
TI - Regulations on statements made for dietary supplements concerning the effect of
the product on the structure or function of the body. Food and Drug
Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is issuing final regulations defining the
types of statements that can be made concerning the effect of a dietary
supplement on the structure or function of the body. The regulations also
establish criteria for determining when a statement about a dietary supplement is
a claim to diagnose, cure, mitigate, treat, or prevent disease. This action is
intended to clarify the types of claims that may be made for dietary supplements
without prior review by FDA and the types of claims that require prior
authorization as health claims or prior approval as drug claims.
PMID- 11010622
TI - Medical devices; laser fluorescence caries detection device. Food and Drug
Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is classifying the laser fluorescence
caries detection device into class II (special controls). The special controls
that will apply to this device are set forth below. The agency is taking this
action in response to a petition submitted under the Federal Food, Drug, and
Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the
amendments), the Safe Medical Devices Act of 1990, and the Food and Drug
Administration Modernization Act of 1997. The agency is classifying this device
into class II (special controls) in order to provide a reasonable assurance of
safety and effectiveness of the device.
PMID- 11010623
TI - Hematology and pathology devices; reclassification; restricted devices; OTC test
sample collection systems for drugs of abuse testing. Food and Drug
Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is reclassifying over-the-counter (OTC)
test sample collection systems for drugs of abuse testing from class III
(premarket approval) into class I (general controls) and exempting them from
premarket notification (510(k)) and current good manufacturing practice (CGMP)
requirements. FDA is also designating OTC test sample collection systems for
drugs of abuse testing as restricted devices under the Federal Food, Drug, and
Cosmetic Act (the act) and establishing restrictions intended to assure consumers
that: The underlying laboratory test(s) are accurate and reliable; the laboratory
performing the test(s) has adequate expertise and competency; and the product has
adequate labeling and methods of communicating test results to consumers.
Finally, FDA is adding a conforming amendment to the existing classification
regulation for specimen transport and storage containers to clarify that it does
not apply to specimen transport and storage containers that are part of an OTC
test sample collection system for the purpose of testing for the presence of
drugs of abuse or their metabolites in a laboratory.
PMID- 11010624
TI - Medical devices; gastroenterology-urology devices; nonimplanted, peripheral
electrical continence device. Food and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is classifying the nonimplanted,
peripheral electrical continence device into class II (special controls). The
special controls that will apply to this device are set forth below. The agency
is taking this action in response to a petition submitted under the Federal Food,
Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of
1976, the Safe Medical Devices Act of 1990, and the Food and Drug Administration
Modernization Act of 1997. The agency is classifying this device into class II
(special controls) in order to provide a reasonable assurance of safety and
effectiveness of the device.
PMID- 11010625
TI - Over-the-counter human drugs; labeling requirements; final rule; technical
amendment. Food and Drug Administration, HHS. Final rule; technical amendment.
AB - The Food and Drug Administration (FDA) is amending the regulation that
established a standardized format and standardized content requirements for the
labeling of over-the-counter (OTC) drug products, and is amending several related
OTC drug product labeling regulations. This amendment corrects and conforms
several aspects of the new labeling requirements to other regulatory provisions
and eliminates unnecessary text from the new labeling regulation.
PMID- 11010626
TI - Diagnostic criteria for traumatic grief.
AB - This article reviews the rationale for the development of diagnostic criteria for
Traumatic Grief. Traumatic Grief is a new nosologic entity that a panel of
experts recently proposed. It is a direct descendent of the concept of pathologic
grief, and it has roots in attachment behavior, separation distress, and
traumatic distress. We present consensus, diagnostic criteria for Traumatic Grief
and discuss them in relation to another recently proposed set of criteria. In
conclusion, we recommend the development of empirically tested, consensus,
diagnostic criteria for Traumatic Grief. Diagnostic criteria would facilitate
early detection and intervention for those bereaved persons afflicted by this
disorder and lead to additional studies of the prevalence, the nature, and the
treatment of the disorder.
PMID- 11010627
TI - Relationship of recollections of first death experience to current death
attitudes.
AB - Previous research (Dickinson, 1992) has investigated adults' memories of their
first childhood experience with death. The present study extended this work to
examine the relationship of various qualitative aspects of the first experience
with death to current death attitudes. College students (196 females, 101 males)
described their first childhood death experience and provided memories of: (a)
who died; (b) whether parental discussion of death had occurred; (c) whether they
had unanswered questions at the time; and (d) whether they had cried at the time.
They then completed the Death Attitude Profile-Revised (DAP-R; Wong, Reker, &
Gesser, 1994). Results indicated that although boys and girls did not respond
differently to the first death experience, gender did appear to moderate the
relationship between the qualities of this experience and current death
attitudes.
PMID- 11010628
TI - Blues fans and suicide acceptability.
AB - Research has neglected the possible impact of the blues music subculture on
suicide acceptability (SA). The sad themes in the blues may attract suicidal
persons and reinforce their suicidal moods and attitudes. The present study
performs the first test of the thesis that associates SA with being a blues fan.
It uses data on a national sample of 961 adults drawn from the General Social
Survey of 1993. The results of a multivariate logistic regression analysis found
that blues fans were no more accepting of suicide than nonfans. However, blues
fanship was found to have substantial indirect effects on SA through its
influence on such factors as lowered religiosity levels, the most important
predictor of SA. Race-specific analyses found more support for the model for
whites than for African Americans.
PMID- 11010629
TI - Making decisions about tube feeding for severely demented patients at the end of
life: clinical, legal, and ethical considerations.
AB - Caregivers and family members are forced to deal with questions about tube
feeding at the end of life for hundreds of thousands of patients suffering from
severe dementia every year. But decisions about accepting or forgoing artificial
nutrition and hydration (ANH) tend to be made in haste, late in the game, without
benefit of full information. Oftentimes, this leads to increased patient
suffering and the inefficient use of medical resources. Surviving family members
and caregivers may experience a haunting sense of guilt, wondering if they made
the right decision at the right time. The professional literature suggests that
forgoing ANH is an entirely appropriate alternative at the end of life. The vast
majority of Americans say they do not want to be tube fed if mortally ill and are
no longer able to eat on their own. Nonetheless, the provision of aggressive
nutrition and hydration support for the severely demented population at the end
of life is the norm in America. If there were more awareness of (a) the burdens
typically associated with ANH; (b) the pathogenesis of terminal dehydration, and;
(c) the medical, legal, and ethical acceptability of terminal dehydration, then
forgoing of ANH might become more commonly considered.
PMID- 11010630
TI - Cardiovascular, orthopedic, and physical medicine diagnostic devices;
reclassification of cardiopulmonary bypass accessory equipment, goniometer
device, and electrode cable devices. Food and Drug Administration, HHS. Final
rule.
AB - The Food and Drug Administration (FDA) is reclassifying from class I into class
II the cardiopulmonary bypass accessory equipment device that involves an
electrical connection to the patient, the goniometer device, and the electrode
cable. FDA is also exempting these devices from the premarket notification
requirements. FDA is reclassifying these devices on its own initiative based on
new information. FDA is taking this action to establish sufficient regulatory
controls that will provide reasonable assurance of the safety and effectiveness
of these devices.
PMID- 11010631
TI - From Chakrabarty to chimeras: the growing need for evolutionary biology in patent
law.
PMID- 11010632
TI - Gastroenterology-urology devices; effective date of requirement for premarket
approval of the penile inflatable implant. Food and Drug Administration, HHS.
Final rule.
AB - The Food and Drug Administration (FDA) is issuing a final rule to require the
filing of a premarket approval application (PMA) or a notice of completion of a
product development protocol (PDP) for the penile inflatable implant, a generic
type of medical device intended for the treatment of erectile dysfunction. This
regulation reflects FDA's exercise of its discretion to require PMA's or PDP's
for preamendments devices and is consistent with FDA's stated priorities and
Congress' requirement that class III devices are to be regulated by FDA's
premarket review. This action is being taken under the Federal Food, Drug, and
Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976 (the
amendments), the Safe Medical Devices Act of 1990, and the Food and Drug
Administration Modernization Act of 1997.
PMID- 11010634
TI - Medical devices; effective date of requirement for premarket approval for three
preamendment class III devices. Food and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is issuing a final rule to retain three
class III preamendment devices in class III and to require the filing of a
premarket approval application (PMA) or a notice of completion of a product
development protocol (PDP) for the following devices: The lung water monitor, the
powered vaginal muscle stimulator, and the stair-climbing wheelchair. The agency
has summarized its findings regarding the degree of risk of illness or injury
designed to be eliminated or reduced by requiring the devices to meet the
statute's approval requirements and the benefits to the public from the use of
the devices.
PMID- 11010633
TI - Are insurance companies liable under the Americans with Disabilities Act?
AB - Federal courts have split on the question of the applicability of the Americans
with Disabilities Act to insurance coverage decisions that insurance companies
make on the basis of disability; they have similarly split on other issues
pertaining to the scope of that Act's application. In deciding whether to read
the Act as prohibiting discrimination in insurance decisions that are often
crucial in the lives of people with disabilities, courts have faced two problems.
First, where it prohibits discrimination in the equal enjoyment of the goods and
services of places of public accommodation, the Act's area of concern may be
limited to the ability of people with disabilities to gain physical access to
facilities; or that area may extend to all forms of disability-based
discrimination in the provision of goods and services. This Comment argues that
the language and legislative history of the Act are consistent only with the
latter view. Second, the provision limiting the Act's applicability to insurance
may create an exemption for all insurance decisions; or it may protect only the
ability of an insurance company to make an insurance decision to the disadvantage
of an insured with a disability where actuarial data support the decision. This
comment argues that the ambiguous language of the limiting provision should be
resolved in favor of the latter view. Legislative history and the broader
background of the history of insurance discrimination law support this
resolution. Consequently, the Act should be interpreted as prohibiting disability
based discrimination by insurance companies in selling insurance policies and as
defining discrimination as making disability-based insurance decisions without
the support of actuarial data. By accepting this interpretation, courts can help
stop the pattern of judicial narrowing of the Act's application through
inappropriately restrictive statutory construction.
PMID- 11010635
TI - Medical devices; reclassification and codification of the stainless steel suture.
Food and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is announcing that it has issued an order
in the form of a letter to Alto Development Corp. (the petitioner) reclassifying
the 316L stainless steel suture for use in abdominal wound closure, intestinal
anastomosis, hernia repair, and sternal closure from class III (premarket
approval) to class II (special controls). The order is being codified in the Code
of Federal Regulations (CFR). Although FDA reclassified the device in 1986, it
inadvertently neglected to publish a notice of the reclassification in the
Federal Register or codify the change in the CFR.
PMID- 11010636
TI - The mainstreaming of alternative medicine.
PMID- 11010637
TI - New Jersey insurers expand cancer care coverage.
PMID- 11010638
TI - Forgotten patients: the mentally ill.
PMID- 11010639
TI - The crisis ahead in long-term care.
PMID- 11010640
TI - Medical devices; reclassification and codification of the nonabsorbable expanded
polytetrafluoroethylene surgical suture. Food and Drug Administration, HHS.
Final rule.
AB - The Food and Drug Administration (FDA) is announcing that it has issued an order
in the form of a letter to W.L. Gore and Associates, Inc., reclassifying the
nonabsorbable expanded polytetrafluoroethylene (ePTFE) surgical suture intended
for use in soft tissue approximation and ligation, including cardiovascular
surgery, from class III (premarket approval) to class II (special controls).
Accordingly, the order is being codified in the Code of Federal Regulations
(CFR).
PMID- 11010641
TI - Nevada State plan; final approval determination. Occupational Safety and Health
Administration (OSHA), U.S. Department of Labor. Final State plan approval-
Nevada.
AB - This document amends OSHA's regulations to reflect the Assistant Secretary's
decision granting final approval to the Nevada State plan. As a result of this
affirmative determination under section 18(e) of the Occupational Safety and
Health Act of 1970, Federal OSHA's standards and enforcement authority no longer
apply to occupational safety and health issues covered by the Nevada plan, and
authority for Federal concurrent jurisdiction is relinquished. Federal
enforcement jurisdiction is retained over any private sector maritime employment,
private sector employers on Indian land, and any contractors or subcontractors on
any Federal establishment where the land is exclusive Federal jurisdiction.
Federal jurisdiction remains in effect with respect to Federal government
employers and employees. Federal OSHA will also retain authority for coverage of
the United States Postal Service (USPS), including USPS employees, contract
employees, and contractor-operated facilities engaged in USPS mail operations.
PMID- 11010642
TI - Determining disability. Railroad Retirement Board. Final rule.
AB - The Railroad Retirement Board (Board) hereby amends its disability regulations to
discontinue the current policy of conducting continuing disability reviews
(CDR's) for medical recovery of disability annuitants in medical improvement not
expected (MINE) cases. The Board has found that these reviews have not been cost
effective and impose an unnecessary burden on the annuitant.
PMID- 11010643
TI - Office of Inspector General; Medicare program; prospective payment system for
hospital outpatient services. Health Care Financing Administration (HCFA), HHS,
and Office of Inspector General (OIG), HHS. Final rule with comment period.
AB - This final rule with comment period implements a prospective payment system for
hospital outpatient services furnished to Medicare beneficiaries, as set forth in
section 1833(t) of the Social Security Act. It also establishes requirements for
provider departments and provider-based entities, and it implements section
9343(c) of the Omnibus Budget Reconciliation Act of 1986, which prohibits
Medicare payment for nonphysician services furnished to a hospital outpatient by
a provider or supplier other than a hospital, unless the services are furnished
under an arrangement with the hospital. In addition, this rule establishes in
regulations the extension of reductions in payment for costs of hospital
outpatient services required by section 4522 of the Balanced Budget Act of 1997,
as amended by section 201(k) of the Balanced Budget Refinement Act of 1999.
PMID- 11010644
TI - Clinical chemistry devices; classification of the biotinidase test system. Food
and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is classifying the biotinidase test system
into class II (special controls). The special control that will apply to this
device is restriction to sale, distribution, and use as a prescription device.
The agency is taking this action in response to a petition submitted under the
Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device
Amendments of 1976, the Safe Medical Devices Act of 1990, and the Food and Drug
Administration Modernization Act of 1997. The agency is classifying these devices
into class II (special controls) in order to provide a reasonable assurance of
the safety and effectiveness of the devices.
PMID- 11010645
TI - Tax treatment of cafeteria plans. Internal Revenue Service (IRS), Treasury. Final
regulations.
AB - This document contains final regulations relating to section 125 cafeteria plans.
The final regulations clarify the circumstances under which a section 125
cafeteria plan election may be changed. The final regulations permit an employer
to allow a section 125 cafeteria plan participant to revoke an existing election
and make a new election during a period of coverage for accident or health
coverage or group-term life insurance coverage.
PMID- 11010646
TI - Medicare program; coverage of, and payment for, paramedic intercept ambulance
services. Health Care Financing Administration (HCFA), HHS. Final rule.
AB - This final rule responds to public comments received on a final rule with comment
period published on January 25, 1999 that implemented section 4531(c) of the
Balanced Budget Act of 1997 concerning Medicare coverage of, and payment for,
paramedic intercept ambulance services in rural communities. It also implements
section 412 of the Medicare, Medicaid, and State Children's Health Insurance
Programs Balanced Budget Refinement Act of 1999 by adding a new definition of a
rural area.
PMID- 11010647
TI - Revision of requirements applicable to albumin (human), plasma protein fraction
(human), and immune globulin (human); confirmation in part and technical
amendment. Food and Drug Administration, HHS. Direct final rule; confirmation in
part and technical amendment.
AB - The Food and Drug Administration (FDA) is confirming in part the direct final
rule that appeared in the Federal Register of May 14, 1999 (64 FR 26282). The
direct final rule amends the biologics regulations by removing, revising, or
updating specific regulations applicable to blood derivative products to be more
consistent with current practices and to remove unnecessary or outdated
requirements. FDA is confirming the provisions for which no significant adverse
comments were received. The agency received significant adverse comments on
certain provisions and is hereby amending Title 21 Code of Federal Regulations to
reinstate the former provisions. In addition, FDA is correcting the precision of
the value for protein concentration that was inadvertently omitted from the
codified section of the direct final rule.
PMID- 11010648
TI - Federal old-age, survivors, and disability insurance and supplemental security
income for the aged, blind, and disabled; evaluating opinion evidence. Social
Security Administration. Final rules.
AB - We are revising the Social Security and Supplemental Security Income (SSI)
regulations concerning the evaluation of medical opinions to clarify how
administrative law judges and the Appeals Council are to consider opinion
evidence from State agency medical and psychological consultants, other program
physicians and psychologists, and medical experts we consult in claims for
disability benefits under titles II and XVI of the Social Security Act (the Act).
We are also defining and clarifying several terms used in our regulations and
deleting other terms.
PMID- 11010649
TI - Medical devices; anesthesiology devices; classification of nitric oxide
administration apparatus, nitric oxide analyzer, and nitrogen dioxide analyzer.
Food and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is classifying the nitric oxide
administration apparatus, nitric oxide analyzer, and nitrogen dioxide analyzer
into class II (special controls). The special control that will apply to these
devices is a guidance document. The agency is taking this action in response to a
petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as
amended by the Medical Device Amendments of 1976 (the amendments), the Safe
Medical Devices Act of 1990, and the Food and Drug Administration Modernization
Act of 1997. The agency is classifying these devices into class II (special
controls) in order to provide a reasonable assurance of the safety and
effectiveness of the devices.
PMID- 11010651
TI - Medical devices; reclassification and codification of
Neodymium:Yttrium:Aluminum:Garnet (Nd:YAG) Laser for peripheral iridotomy. Food
and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is announcing that it has issued an order
in the form of a letter to Intelligent Surgical Lasers, Inc. (ISL), (now doing
business as Escalon Medical Corporation), reclassifying the
Neodymium:Yttrium:Aluminum:Garnet (Nd:YAG) Laser for use in peripheral iridotomy
from class III to class II (special controls). Accordingly, the order is now
being codified in the Code of Federal Regulations (CFR) as described below.
PMID- 11010650
TI - Medical devices; exemptions from premarket notification; class II devices;
vascular tunnelers. Food and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is publishing an order granting in part a
petition requesting exemption from the premarket notification requirements for
vascular tunnelers with certain limitations. This rule will exempt from premarket
notification stainless steel vascular tunnelers of single unit construction. FDA
is publishing this order in accordance with procedures established by the Food
and Drug Administration Modernization Act of 1997 (FDAMA).
PMID- 11010652
TI - Gastroenterology-urology devices: reclassification of the penile rigidity
implant. Food and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is reclassifying the penile rigidity
implant from class III to class II when intended to provide penile rigidity in
men diagnosed as having erectile dysfunction. The special control is the FDA
guidance document entitled "Guidance for the Content of Premarket Notifications
for Penile Rigidity Implants." This action is taken on FDA's own initiative based
on new information. This action is being taken under the Federal Food, Drug, and
Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976, the
Safe Medical Devices Act of 1990, and the FDA Modernization Act of 1997.
PMID- 11010653
TI - Medical device reporting: manufacturer reporting, importer reporting, user
facility reporting, distributor reporting. Food and Drug Administration, HHS.
Final rule.
AB - The Food and Drug Administration (FDA) is amending its regulations governing
reporting by manufacturers, importers, distributors and health care (user)
facilities of adverse events related to medical devices. Amendments are being
made to implement revisions to the Federal Food, Drug, and Cosmetic Act (the act)
as amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA).
PMID- 11010654
TI - Amendment of various device regulations to reflect current American Society for
Testing and Material citations. Food and Drug Administration, HHS. Direct final
rule.
AB - The Food and Drug Administration (FDA) is amending certain references in various
medical device regulations. The amendments update the references in those
regulations to various standards of the American Society for Testing and
Materials (ASTM) to reflect the current standards designations. Elsewhere in this
issue of the Federal Register, FDA is publishing a companion proposed rule, under
FDA's usual procedures for notice-and-comment, to provide a procedural framework
to finalize the rule in the event that the agency receives any significant
adverse comment and withdraws the direct final rule.
PMID- 11010655
TI - Medical devices; exemption from premarket notification and reserved devices;
class I. Food and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is amending its classification regulations
to designate class I devices that are exempt from the premarket notification
requirements, subject to certain limitations, and to designate those class I
devices that remain subject to premarket notification requirements under the new
statutory criteria for premarket notification requirements. The devices FDA is
designating as exempt do not include class I devices that have been previously
exempted by regulation from the premarket notification requirements. This action
is being taken under the Federal Food, Drug, and Cosmetic Act (the act), as
amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe
Medical Devices Act of 1990 (SMDA), and the FDA Modernization Act of 1997
(FDAMA). FDA is taking this action in order to implement a requirement of FDAMA.
Elsewhere in this issue of the Federal Register, FDA is announcing that it is
withdrawing proposed rules to revoke existing exemptions from premarket
notification for two devices.
PMID- 11010656
TI - New drug applications; drug master files. Food and Drug Administration, HHS.
Final rule.
AB - The Food and Drug Administration (FDA) is revising its regulation governing drug
master files (DMF's). FDA is removing the provision for submitting Type I DMF's
and will no longer permit information submitted in a Type I DMF to be
incorporated by reference in investigational new drug applications (IND's), new
drug applications (NDA's), abbreviated new drug applications (ANDA's), or
amendments or supplements to any of these. This rule is intended to eliminate
submissions of information that are not necessary either to conduct inspections
of manufacturing facilities or to review the chemistry, manufacturing, and
controls sections of IND's, NDA's, and abbreviated applications.
PMID- 11010657
TI - Per diem for nursing home care of veterans in State homes. Department of Veterans
Affairs. Final rule.
AB - This document amends regulations regarding the payment of per diem to State homes
that provide nursing home care to eligible veterans. The intended effect of the
final rule is to ensure that veterans receive high quality care in State homes.
PMID- 11010658
TI - The myth of the replacement child: parents' stories and practices after perinatal
death.
AB - Parents bereaved by perinatal death adapt to their losses in different ways. When
bereaved parents give birth to a child or children subsequent to a perinatal
death, their constructions of the family necessarily change. The subsequent child
is thought to be at risk of psychopathology (the replacement child syndrome) if
parents have not sufficiently grieved their losses. This qualitative interview
study examines the family stories told by bereaved parents, with particular
attention to how parents represent the dead child and subsequent children in the
current family structure. We categorized parents' stories as those which
suggested that parents replaced the loss by an emphasis on parenting subsequent
children, or maintained a connection to the dead child through storytelling and
ritual behavior. The two ways in which parents maintained the connection were to
preserve the space in the family that the dead child would have inhabited, or to
create an on-going relationship with the dead child for themselves and their
subsequent children. There seem to be multiple paths to parenting through
bereavement. The place of rituals and memorial behavior is also examined.
PMID- 11010659
TI - Does writing about the bereavement lessen grief following sudden, unintentional
death?
AB - Writing about traumatic events produces improvement in an array of areas
including physical and psychological functioning. To see if these improvements
extended to improved bereavement recovery after the accidental or homicidal death
of a loved one, 64 undergraduates (51 women, 13 men) began, and 44 completed, a
writing project. At pretest, they completed measures of depression, anxiety,
grief, impact, and non-routine health visits. Then, they were randomly assigned
to write about either the bereavement experience (profound condition), or
innocuous topics (trivial condition). They wrote for 15 minutes a day for four
days, then completed the same measures a second time (posttest). Six weeks later,
they were mailed the same measures again (follow-up). A 2 (CONDITION: Profound
versus Trivial) x 3 (Time: Pre-, Post-, or Follow-up) MANOVA yielded a
significant main effect for time, but no main effect for condition and no
interaction. Follow-up ANOVAs indicated that, across conditions, from pretest to
follow-up testing participants reported less anxiety and depression, less impact,
greater grief recovery, but about the same health center visits. A 2 (CONDITION)
x 4 (Writing Day) MANOVA and follow-up tests indicated that those in the profound
condition reported less subjective distress from Day 1 to Day 3, compared to
those in the trivial condition. Combined with Kovac and Range (1999), present
results suggest that writing projects may be more beneficial to those
experiencing the unique bereavement of suicidal death, rather than those
experiencing the nonintentional death of a loved one by accident or homicide.
PMID- 11010660
TI - Hospice and assisted suicide: the structure and process of an inherent dilemma.
AB - The hospice philosophy involves making terminal patients as comfortable as
possible, empowering them with control of the time they have left, but neither
hastening nor postponing death. The passage of Oregon's Death with Dignity Act in
November of 1994, and the failure of the 1997 ballot measure to repeal it, made
physician-assisted suicide another option for terminally ill people in that
state, and focused increased attention on a conflict seemingly inherent in the
hospice philosophy. We conducted interviews with 60 hospice providers, 43 in
Oregon and, for comparison, 17 in the northeast, for their responses to this
situation. The data reported here reflect some of the social and individual
influences that come to bear as hospice providers attempt to resolve their
dilemma.
PMID- 11010661
TI - Shame and suicide: a case study.
AB - Building on a recent paper by Lester (1997) on shame and suicide, a case is
presented of a woman who made a serious attempt to kill herself, motivated in
large part by shame. The therapeutic strategies employed are described, and the
case brought to a successful resolution.
PMID- 11010662
TI - Medicare and state health care programs: fraud and abuse; clarification of the
initial OIG safe harbor provisions and establishment of additional safe harbor
provisions under the anti-kickback statute. Office of Inspector General (OIG),
HHS. Final rule.
AB - This final rule serves both to add new safe harbor provisions under the Federal
and State health care programs' anti-kickback statute, as authorized under
section 14 of Public Law 100-93, the Medicare and Medicaid Patient and Program
Protection Act of 1987, and to clarify various aspects of the original safe
harbor provisions now codified in 42 CFR part 1001 (originally proposed in RIN
0991-AA74). Specifically, this final rule modifies the original set of final safe
harbor provisions codified in 42 CFR 1001.952 to give greater clarity to that
rulemaking's original intent. In addition, this final rule sets forth an expanded
set of safe harbor provisions designed to protect additional payment and business
practices from criminal prosecution or civil sanctions under the anti-kickback
provisions of the statute.
PMID- 11010663
TI - Medicare and Medicaid programs; programs of all-inclusive care for the elderly
(PACE). Health Care Financing Administration (HCFA), HHS. Interim final rule with
comment period.
AB - This rule establishes requirements for Programs of All-inclusive Care for the
Elderly (PACE) under Medicare and Medicaid. These are pre-paid, capitated
programs for beneficiaries who meet special eligibility requirements and who
elect to enroll. Programs must apply for approval and are evaluated in terms of
specific criteria. Only a limited number of programs can be approved. Priority
consideration will be given to applicants that have been operating under ongoing
PACE demonstration projects.
PMID- 11010664
TI - Medicare and Medicaid programs; religious nonmedical health care institutions and
advance directives. Health Care Financing Administration (HCFA), HHS. Interim
final rule with comment period.
AB - This rule deletes all references to Christian Science sanatoria and sets forth
the Medicare requirements for coverage and payment of services furnished by
religious nonmedical health care institutions. It also sets forth the conditions
of participation that religious nonmedical health care institutions must meet
before they can participate in Medicare. It sets forth the methods we will use to
pay religious nonmedical health care institutions and monitor expenditures for
religious nonmedical health care institution services. Additionally, the rule
presents the rules governing optional coverage of religious nonmedical health
care institution services by States under the Medicaid program.
PMID- 11010665
TI - Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992;
policies, requirements, and administrative procedures. Food and Drug
Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is issuing a final rule to set forth
procedures and requirements implementing the Prescription Drug Marketing Act of
1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA) and
the FDA Modernization Act of 1997 (the Modernization Act). The final rule sets
forth requirements for the reimportation and wholesale distribution of
prescription drugs; the sale, purchase, or trade of, or the offer to sell,
purchase, or trade, prescription drugs that were purchased by hospitals or health
care entities, or donated to charitable organizations; and the distribution of
prescription drug samples. FDA is also amending certain sections of the
regulations entitled "Guidelines for State Licensing of Wholesale Prescription
Drug Distributors" to make them consistent with this final regulation.
PMID- 11010666
TI - Establishment of a Medical Implant Communications Service in the 402-405 MHz
band. Federal Communications Commission. Final rule.
AB - This document establishes a Medical Implant Communications Service (MICS)
operating in the 402-405 MHz band. MICS operations will consist of high-speed,
ultra-low power, non-voice transmissions to and from implanted medical devices
such as cardiac pacemakers and defibrillators. The rules will allow use of newly
developed, life-saving medical technology without harming other users of the
frequency band.
PMID- 11010667
TI - It's only skin deep: FDA regulation of skin care cosmetics claims.
PMID- 11010668
TI - The third wave of federal tort reform: protecting the public or pushing the
constitutional envelope?
PMID- 11010669
TI - Approval and promulgation of Hospital/Medical/Infectious Waste Incinerators:
State Plan for designated facilities and pollutants: Idaho. Environmental
Protection Agency (EPA). Direct final rule.
AB - EPA is approving the State of Idaho's section 111(d) State Plan for controlling
emissions from existing Hospital/Medical/Infectious Waste Incinerators (HMIWI).
The plan was submitted on December 16, 1999, to fulfill the requirements of
sections 111(d) and 129 of the Clean Air Act. The State Plan adopts and
implements the Emissions Guidelines applicable to existing HMIWIs, and
establishes emission limits and controls for sources constructed on or before
June 20, 1996. EPA has determined that Idaho's State Plan meets CAA requirements
and hereby approves this State Plan, thus making it federally enforceable.
PMID- 11010670
TI - Placement of gamma-butyrolactone in List I of the Controlled Substances Act (21
U.S.C. 802(34)). Drug Enforcement Administration, Justice. Final rule.
AB - Public Law 106-172, signed into law on February 18, 2000, and known as the
"Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 1999,"
amends section 102(34) of the Controlled Substances Act as amended (CSA) by
designating gamma-butyrolactone (GBL), the precursor to gamma-hydroxybutyric acid
(GHB), as a List I chemical. Reflecting this change in stature, the Drug
Enforcement Administration (DEA) is amending its regulation to reflect the status
of GBL as a List I chemical subject to the requirements of the CSA and its
regulations. Establishment of a threshold for GBL will be the subject of a
separate rulemaking. Therefore, unless and until a threshold is established, any
distribution of GBL is a regulated transaction as described by 21 CFR
1300.02(b)(28). All handlers of GBL must comply with the CSA regulatory
requirements pertaining to List I chemicals as described in the body of this
document.
PMID- 11010671
TI - Health care programs: fraud and abuse; revised OIG civil money penalties
resulting from public law 104-191. Office of Inspector General (OIG), HHS. Final
rule.
AB - This final rule revises the OIG's civil money penalty (CMP) authorities, in
conjunction with new and revised provisions set forth in the Health Insurance
Portability and Accountability Act of 1996. Among other provisions, this final
rulemaking codifies new CMPs for excluded individuals retaining ownership or
control interest in an entity; upcoding and claims for medically unnecessary
services; offering inducements to beneficiaries; and false certification of
eligibility for home health services. This rule also codifies a number of
technical corrections to the regulations governing OIG's sanction authorities.
PMID- 11010672
TI - Biofeedback in the treatment of urinary incontinence in adults.
PMID- 11010673
TI - FDG positron emission tomography in head and neck cancer.
PMID- 11010674
TI - High dose lymphoablative therapy (HDLT) with or without stem cell rescue for
treatment of severe autoimmune diseases.
PMID- 11010675
TI - Intradiscal electrothermal therapy for chronic low back pain.
PMID- 11010676
TI - Pelvic floor electrical stimulation in the treatment of adult urinary
incontinence.
PMID- 11010678
TI - Cardiology.
PMID- 11010677
TI - Intrathecal baclofen pump implantation.
PMID- 11010679
TI - Standards for privacy of individually identifiable health information. Office of
the Assistant Secretary for Planning and Evaluation, DHHS. Proposed rule.
AB - This rule proposes standards to protect the privacy of individually identifiable
health information maintained or transmitted in connection with certain
administrative and financial transactions. The rules proposed below, which would
apply to health plans, health care clearinghouses, and certain health care
providers, propose standards with respect to the rights individuals who are the
subject of this information should have, procedures for the exercise of those
rights, and the authorized and required uses and disclosures of this information.
The use of these standards would improve the efficiency and effectiveness of
public and private health programs and health care services by providing enhanced
protections for individually identifiable health information. These protections
would begin to address growing public concerns that advances in electronic
technology in the health care industry are resulting, or may result, in a
substantial erosion of the privacy surrounding individually identifiable health
information maintained by health care providers, health plans and their
administrative contractors. This rule would implement the privacy requirements of
the Administrative Simplification subtitle of the Health Insurance Portability
and Accountability Act of 1996.
PMID- 11010680
TI - No known cause: leukemia research.
PMID- 11010681
TI - Medicare program; coverage of ambulance services and vehicle and staff
requirements. Health Care Financing Administration (HCFA), HHS. Final rule with
comment period.
AB - This final rule with comment period revises and updates Medicare policy
concerning ambulance services. It identifies destinations to which ambulance
services are covered, establishes requirements for the vehicles and staff used to
furnish ambulance services, and clarifies coverage of nonemergency ambulance
services for Medicare beneficiaries. This rule also implements section 4531 (c)
of the Balanced Budget Act of 1997 concerning Medicare coverage for paramedic
intercept services in rural communities.
PMID- 11010682
TI - Special Supplemental Nutrition Program for Women, Infants and Children (WIC): non
discretionary funding provisions of the William F. Goodling Child Nutrition
Reauthorization Act of 1998. Food and Nutrition Service, USDA. Final rule.
AB - This final rule incorporates into the WIC program regulations numerous non
discretionary funding provisions mandated in the William F. Goodling Child
Nutrition Reauthorization Act of 1998. This rule revises and expands backspend
and spendforward authority, conversion of funds, multipurpose/infrastructure
grants and the use of food funds for the purchase of breast pumps. The rule also
revises nutrition services and administration expenditure standards and expands
the timing for the use of vendor and participant collections. The provisions in
this rule provide greater flexibility for State agencies in the operation of WIC
program relating to funds management.
PMID- 11010683
TI - Chronic beryllium disease prevention program. Office of Environment, Safety and
Health, Department of Energy. Final rule.
AB - The Department of Energy (DOE) is today publishing a final rule to establish a
chronic beryllium disease prevention program (CBDPP) to reduce the number of
workers currently exposed to beryllium in the course of their work at DOE
facilities managed by DOE or its contractors, minimize the levels of, and
potential for, exposure to beryllium, and establish medical surveillance
requirements to ensure early detection of the disease. This program improves and
codifies provisions of a temporary CBDPP established by DOE directive in 1997.
PMID- 11010684
TI - Special Supplemental Nutrition Program for Women, Infants, and Children (WIC):
bloodwork requirements. Food and Nutrition Service, USDA. Final rule.
AB - This final rule amends regulations governing the Special Supplemental Nutrition
Program for Women, Infants, and Children (WIC) to allow State agencies the option
to defer the collection of blood test data for up to 90 days after the date of
certification, so long as the applicant is determined to have at least one
qualifying nutrition risk factor at the time of certification. In addition, this
final rule will expand the current regulatory standard of the maximum age of
blood test data used to assess nutritional risk for WIC certification. Although
blood tests may no longer be a mandatory part of each WIC applicant's
certification intake process, such tests are still required for the purposes of
assessing nutritional status, nutrition surveillance, providing nutrition
education, further tailoring food packages to meet nutritional needs, and
referring to appropriate health and social services in the community.
PMID- 11010686
TI - Medicare program; solvency standards for provider-sponsored organizations. Health
Care Financing Administration (HCFA), HHS. Final rule.
AB - The Balanced Budget Act of 1997 established a new Medicare+Choice (M+C) program
that offers eligible individuals Medicare benefits through enrollment in one of
an array of private health plans that contract with us. Among the new options
available to Medicare beneficiaries is enrollment in a provider-sponsored
organization (PSO). This final rule revises and responds to comments on solvency
standards that certain entities must meet to contract as PSOs under the new M+C
program. These standards, originally established in an interim final rule
published on May 7, 1998, apply to PSOs that have received a waiver of the
requirement that M+C organizations must be licensed by a State as risk-bearing
entities.
PMID- 11010685
TI - Approval of Hospital/Medical/Infectious Waste Incinerator State Plan for
designated facilities and pollutants: Indiana. Environmental Protection Agency
(EPA). Direct final rule.
AB - EPA is approving Indiana's State Plan for Hospital/Medical/Infectious Waste
Incinerators (HMIWI), submitted on September 30, 1999. The State Plan adopts and
implements the Emissions Guidelines (EG) applicable to existing HMIWIs. This
approval means that EPA finds the State Plan meets Clean Air Act (Act)
requirements. Once effective, this approval makes the State Plan federally
enforceable.
PMID- 11010687
TI - Tricare; Civilian Health and Medical Program of the Uniformed Services (CHAMPUS);
nonavailability statement requirement for maternity care. Office of the
Secretary, DoD. Interim final rule.
AB - This interim final rule implements Section 712(c) of the National Defense
Authorization Act for Fiscal Year 2000 (Pub. L. No. 106-65), which requires that
a nonavailability-of-health-care statement shall be required for a non-enrolled
beneficiary for TRICARE cost-share of maternity care services related to
outpatient prenatal, outpatient or inpatient delivery, and outpatient post-partum
care subsequent to the visit which confirms the pregnancy. The Act reestablishes
a requirement which was previously eliminated under the broad direction of The
National Defense Authorization Act of FY 1997, section 734, which removed
authority for nonavailability statements (NASs) for outpatient services.
Therefore, the Act changes the existing provisions require an NAS for inpatient
delivery but do not require an NAS for outpatient prenatal and post-partum care.
The change will significantly contribute to continuity of care for maternity
patients. In furtherance of that principle, and consistent with the previous
policy, an NAS for maternity care shall not be required when a beneficiary has
other health insurance for primary coverage. This is being issued as an interim
final rule in order to comply with the statutory mandate. Public comments,
however, are invited and will be considered in connection with possible revisions
to this rule.
PMID- 11010688
TI - Family and medical leave. Office of Personnel Management. Final rule.
AB - The Office of Personnel Management is issuing final regulations on the Family and
Medical Leave Act of 1993 to ensure that both employees' and agencies' rights are
protected and their responsibilities fulfilled.
PMID- 11010689
TI - Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992;
policies, requirements, and administrative procedures; delay of effective date;
reopening of administrative record. Food and Drug Administration, HHS. Final
rule; delay of effective date; reopening of administrative record.
AB - The Food and Drug Administration (FDA) is delaying until October 1, 2001, the
effective date and reopening the administrative record to receive additional
comments regarding certain requirements of a final rule published in the Federal
Register of December 3, 1999 (64 FR 67720). The other provisions of the final
rule become effective on December 4, 2000. The final rule implements the
Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription
Drug Amendments of 1992 (PDA) and the FDA Modernization Act of 1997 (the
Modernization Act). FDA is delaying the effective date for certain requirements
relating to wholesale distribution of prescription drugs by distributors that are
not authorized distributors of record. FDA is also delaying the effective date of
another requirement that would prohibit blood centers functioning as "health care
entities" to act as wholesale distributors of blood derivatives. The agency is
taking this action to address numerous concerns about the provisions raised by
affected parties.
PMID- 11010690
TI - Medical devices; revocation of cardiac pacemaker registry. Food and Drug
Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is issuing a final rule to revoke a
regulation requiring a cardiac pacemaker registry. The registry, which was
mandated by the Deficit Reduction Act of 1984, requires any physician and any
provider of services who requests or receives Medicare payment for an
implantation, removal, or replacement of permanent cardiac pacemaker devices and
pacemaker leads to submit certain information to the registry. The information is
used by FDA to track the performance of permanent cardiac pacemakers and
pacemaker leads and by the Health Care Finance Administration (HCFA) to
administer its Medicare payment program for these devices. This action is being
taken to implement an act to Repeal An Unnecessary Medical Device Reporting
Requirement passed by Congress in 1996 to remove the cardiac pacemaker registry
to eliminate duplicative and unnecessary reporting.
PMID- 11010691
TI - Progestational drug products for human use; requirements for labeling directed to
the patient. Food and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is revoking its regulation requiring
patient labeling for progestational drug products. Patient labeling had been
required to inform patients of an increased risk of birth defects reported to be
associated with the use of these drugs during the first 4 months of pregnancy.
FDA concluded that, based on a review of the scientific data, such labeling for
all progestogens is not warranted. In addition, the diversity of drugs that can
be described as progestational and the diversity of conditions these drugs may be
used to treat make it inappropriate to consider these drugs a single class for
labeling purposes. This action is intended to provide consumers with more
appropriate labeling for certain drug products.
PMID- 11010692
TI - Medicare program; suggestion program on methods to improve Medicare efficiency.
Health Care Financing Administration (HCFA), HHS. Final rule with comment period.
AB - This final rule with comment period establishes a program to encourage
individuals to submit suggestions that could improve the efficiency of the
Medicare program. The rule implements section 203(c) of the Health Insurance
Portability and Accountability Act of 1996. The intent of this rule is to
encourage suggestions and to award, if we deem appropriate, monetary payments to
individuals for suggestions that improve efficiency and produce monetary savings
to the Medicare program.
PMID- 11010693
TI - Medicare program; revisions to payment policies under the physician fee schedule
for calendar year 2000. Health Care Financing Administration (HCFA), HHS. Final
rule with comment period.
AB - This final rule makes several changes affecting Medicare Part B payment. The
changes include: implementation of resource-based malpractice insurance relative
value units (RVUs); refinement of resource-based practice expense RVUs; payment
for physician pathology and independent laboratory services; discontinuous
anesthesia time; diagnostic tests; prostate screening; use of CPT modifier -25;
qualifications for nurse practitioners; an increase in the work RVUs for
pediatric services; adjustments to the practice expense RVUs for physician
interpretation of Pap smears; and revisions to the work RVUs for new and revised
CPT codes for calendar year 1999 and a number of other changes relating to coding
and payment. Furthermore, we are finalizing the 1999 interim physician work RVUs
and are issuing interim RVUs for new and revised codes for 2000. This final rule
solicits public comments on the second 5-year refinement of work RVUs for
services furnished beginning January 1, 2002 and requests public comments on
potentially misvalued work RVUs for all services in the CY 2000 physician fee
schedule. This final rule also conforms the regulations to existing law and
policy regarding: removal of the x-ray as a prerequisite for chiropractic
manipulation; the exclusion of payment for assisted suicide; and optometrist
services. This final rule also announces the calendar year 2000 Medicare
physician fee schedule conversion factor under the Medicare Supplementary
Insurance (Part B) program as required by section 1848(d) of the Social Security
Act. The 2000 Medicare physician fee schedule conversion factor is $36.6137.
PMID- 11010694
TI - Age, the stress process, and physical distress: the role of distal stressors.
AB - OBJECTIVES: This article examines the nature of distal stressors over a 15-year
period and the extent to which they contribute to the explanation of additional
variation in the life stress model. METHODS: The study uses data collected from a
community sample of adults to test specific hypotheses. RESULTS: Findings show
that (a) distal stressors significantly increase variance explained in physical
symptoms and maintain a direct effect on physical symptoms, (b) recent stressors
mediate the effects of distal stressors on distress, and (c) social resources
have direct and mediating effects on physical distress. Variations exist for
different age groups or life stages. DISCUSSION: The implications of the findings
are discussed in the context of life course, theoretical issues of temporality,
types of stressors, and the role of social resources. The major conclusion is
that there are multiple pathways to distress that differ for different stages in
the life course.
PMID- 11010695
TI - Factors that contribute to positive perceived health in an older population.
AB - This study explored the extent to which factors commonly associated with negative
outcomes of aging also predicted positive perceived health in a group of
community-dwelling older people. Questionnaires originally administered during a
randomized trial of HMO's outpatient group visit program supplied data from
approximately 700 participants. Stepwise modeling identified significant factors
within categories of predictors of perceived health. Hierarchical multiple linear
regression then modeled the incremental importance of theoretically-derived
categories of factors. Many but not all of the factors previously associated with
negative outcomes of aging also predicted positive perceived health, accounting
for 38% of the variation. The most important predictors were fewer chronic
conditions and no worsening of those conditions, mobility and better physical
performance status, and the absence of depression. Gender, limitations in daily
living activities, dementia, and utilization of services had little effect. The
categories of f factors associated with positive perceived health had cumulative,
interdependent effects.
PMID- 11010696
TI - Occurrence of hip fractures and socioeconomic position.
AB - OBJECTIVES: The purpose of this study was to determine hip fracture incidence in
the older U.S. White population as a function of their socioeconomic position.
METHODS: A sample of 5,161 White, hip fracture cases, 50 years and older, was
selected using data from the National Hospital Discharge Survey for 1989-91.
Median annual household income by ZIP Code of residence based on the 1990 Census
was used as the measure of socioeconomic position. Fracture rates were calculated
by age, sex, and income groups ranging from under $20,000 to $40,000 and more.
RESULTS: A weighted, least squares analysis found a significant linear decrease
in rates with increasing income after controlling for age and sex. CONCLUSIONS:
The results indicate that hip fracture incidence varies as a function of the
income level of the ZIP Code area where the population resides. Implications for
targeting prevention programs within local areas with low median income are
discussed.
PMID- 11010697
TI - A health and demographic profile of noninstitutionalized older Americans residing
in environments with home modifications.
AB - OBJECTIVES: In this analysis the authors investigate the demographic
characteristics, the health conditions/events, and the disabilities of community
dwelling Americans 70 years of age and older that are associated with residing in
environments with specific home modifications. METHODS: Data from a large
population-based study of the elderly are used to estimate logistic regression
equations that reveal profiles of older individuals who are likely to have
distinct home modifications. RESULTS: Having diseases such as diabetes and
stroke, having experienced a hip fracture, a fall or a joint replacement, and
having greater limitations with activities of daily living raise the likelihood
of having home modifications. Low income, Hispanic, and African American elderly
appear underrepresented among those with modifications. DISCUSSION: The authors
conclude that specialized housing alternatives will be an increasingly important
issue in the future as individuals aim to achieve and maintain the delicate
balance between their functional ability and their living environment.
PMID- 11010698
TI - Race and ethnic variation in the disablement process.
AB - OBJECTIVES: This analysis examines ethnoracial group differences in the
transition from health to disability. METHODS: Using data from the AHEAD study,
the authors examine the relative influence of each stage in the disablement
process in the evolution of ethnoracial group differences in basic and
instrumental disability. RESULTS: Predisposing factors account for disability
differences between Whites and other Latinos, whereas excess disability among
African Americans stems from their higher level of cognitive limitation. The
excess disability of Mexican Americans arises from their higher level of physical
limitations. The data also reveal a larger impact of medical conditions and
physical limitations on acquisition of disability among African Americans and
Mexican Americans. This article demonstrates the importance of cognitive status
in the disablement process, especially in ethnoracial group differences.
DISCUSSION: The authors discuss the practical implications for health care
delivery to non-White elders and the theoretical implications for understanding
the complexities of disablement.
PMID- 11010699
TI - Outcomes of a small group educational intervention for urinary incontinence:
episodes of incontinence and other urinary symptoms.
AB - OBJECTIVES: This community-based intervention to reduce urinary incontinence (UI)
in elderly women used a small group educational approach. This article reports on
change in episodes of incontinence and other urinary symptoms. METHODS:
Participants were randomly assigned to intervention or wait control condition.
This article is restricted to 49 intervention and 59 control participants with
acceptable diaries. RESULTS: There was a significant treatment effect for a
number of incontinent episodes. In the intervention group, 61% had a 50% or
greater reduction in episodes, with more than one third having 100% reduction;
38% of the control group had a reduction of 50% or greater. One year postprogram,
75% of treated women reported subjective improvement. There was a reduction in
frequency of daily, but not nocturnal, micturition. DISCUSSION: This community
based intervention is an encouraging option for behavioral treatment of UI.
Public health models may be particularly appropriate with moderate levels of
urinary incontinence.
PMID- 11010700
TI - Must poor kids have bad teeth?
PMID- 11010701
TI - General and plastic surgery devices; classification of the nonresorbable
gauze/sponge for external use, the hydrophilic wound dressing, the occlusive
wound dressing, and the hydrogel wound dressing. Food and Drug Administration,
HHS. Final rule.
AB - The Food and Drug Administration (FDA) is classifying the nonresorbable
gauze/sponge for external use, the hydrophilic wound dressing, the occlusive
wound dressing, and the hydrogel wound dressing into class I (general controls).
FDA is also exempting these devices from premarket notification procedures. This
action is being taken under the Federal Food, Drug, and Cosmetic Act (the act),
as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the
Safe Medical Devices Act of 1990 (SMDA), and the Food and Drug Administration
Modernization Act of 1997 (FDAMA).
PMID- 11010702
TI - Human drugs and biologics; determination that informed consent is NOT feasible or
is contrary to the best interests of recipients; revocation of 1990 interim final
rule; establishment of new interim final rule. Food and Drug Administration, HHS.
Interim final rule; opportunity for public comment.
AB - The Food and Drug Administration (FDA) is revoking its 1990 interim final
regulations that permitted the Commissioner of Food and Drugs (the Commissioner)
to determine that obtaining informed consent from military personnel for the use
of an investigational drug or biologic is not feasible in certain situations
related to military combat. FDA also is issuing a new interim final rule
addressing waiver of informed consent in military operations. FDA is taking these
actions based on its analysis and consideration of all relevant facts, including
its evaluation of the Department of Defense's (DOD) experience during the Persian
Gulf War, its evaluation of the comments received by the agency in response to
the agency's July 31, 1997, request for comments on whether the agency should
revise or revoke the interim regulations, and the enactment of the Strom Thurmond
National Defense Authorization Act for Fiscal Year 1999 (the Defense
Authorization Act). Under the Defense Authorization Act, the President is
authorized to waive the Federal Food, Drug, and Cosmetic Act's (the act) informed
consent requirements in military operations if the President finds that obtaining
consent is infeasible or contrary to the best interests of recipients and on an
additional ground that obtaining consent is contrary to national security
interests. In light of the enactment of the Defense Authorization Act, with an
immediate effective date, and because the President could be called upon to make
a waiver determination for military personnel engaged in a specific military
operation at any time, the agency believes that it is critical to have in place
adequate criteria and standards for the President to apply in making an informed
consent waiver determination. Therefore, FDA is issuing a new interim final
regulation with an immediate effective date to establish criteria and standards
for the President to apply in making a determination that informed consent is not
feasible or is contrary to the best interests of the individual recipients.
PMID- 11010703
TI - Organ Procurement and Transplantation Network. Health Resources and Services
Administration, HHS. Final rule.
AB - This document sets forth improvements to the final rule governing the operation
of the Organ Procurement and Transplantation Network (OPTN), published in 1998.
It reflects the advice of a panel convened by the National Academy of Science's
Institute of Medicine, as called for in the Department's appropriation act for
1999. It also reflects comments on the 1998 rule and consultation with
representatives of the organ transplantation community, as recommended in the
same legislation; and it summarizes new transplant data developed in the period
since enactment of the appropriations act.
PMID- 11010704
TI - Enrollment--provision of hospital and outpatient care to veterans. Department of
Veterans Affairs. Final rule.
AB - This document amends VA's medical regulations. The Veterans' Health Care
Eligibility Reform Act of 1996 mandates that VA implement a national enrollment
system to manage the delivery of healthcare services. Accordingly, the medical
regulations are amended to establish provisions consistent with this mandate.
Starting October 1, 1998, most veterans were required to be enrolled in the VA
healthcare system as a condition of receiving VA hospital and outpatient care.
Veterans will be allowed to apply to be enrolled at any time. They will be
eligible to be enrolled based on funding availability and their priority status.
In accordance with statutory provisions, the final rule also states that some
categories of veterans are eligible for VA hospital and outpatient care even if
not enrolled. This document further establishes a "medical benefits package"
setting forth, with certain exceptions, the hospital and outpatient care that
will be provided to enrolled veterans and certain other veterans. Moreover, this
document announces that VA will enroll all 7 priority categories of veterans for
the period October 1, 1999 through September 30, 2000, unless it is necessary to
change this determination by a subsequent rulemaking document.
PMID- 11010705
TI - Currently effective Indian Health Service eligibility regulations. Indian Health
Service, HHS. Republication of currently effective Indian Health Service
eligibility regulations.
AB - The HHS is publishing in the Federal Register, final regulations governing
eligibility for services from the Indian Health Service. The eligibility
regulations currently codified at 42 CFR part 36 are under a congressional
moratorium. Republishing the regulations that are currently in effect while the
codified regulations are under moratorium is being done for the convenience of
the public and in conformance with the requirement of the Administrative
Procedure Act, 5 U.S.C. 552(a)(1), that the Code of Federal Regulations (CFR)
must contain currently effective regulations.
PMID- 11010706
TI - Food labeling: health claims; soy protein and coronary heart disease. Food and
Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is authorizing the use, on food labels and
in food labeling, of health claims on the association between soy protein and
reduced risk of coronary heart disease (CHD). Based on its review of evidence
submitted with comments to the proposed rule, as well as evidence described in
the proposed rule, the agency has concluded that soy protein included in a diet
low in saturated fat and cholesterol may reduce the risk of CHD by lowering blood
cholesterol levels.
PMID- 11010708
TI - Medicare program; revision to accrual basis of accounting policy. Health Care
Financing Administration (HCFA), HHS. Final rule.
AB - Medicare policy provides that payroll taxes that a provider becomes obligated to
remit to governmental agencies are included in allowable costs only in the cost
reporting period in which payment (upon which the payroll taxes are based) is
actually made to an employee. Therefore, for payroll accrued in 1 year but not
paid until the next year, the associated payroll taxes are not an allowable cost
until the next year. This final rule provides for an exception when payment would
be made to the employee in the current year but for the fact the regularly
scheduled payment date is after the end of the year. In that case, the rule
requires allowance in the current year of accrued taxes on payroll that is
accrued through the end of the year but not paid until the beginning of the next
year, thus allowing accrued taxes on end-of-the year payroll in the same year
that the accrual of the payroll itself is allowed. The effect of this rule is not
on the allowability of cost but rather only on the timing of payment; that is,
the cost of payroll taxes on end-of-the-year payroll is allowable in the current
period rather than in the following period.
PMID- 11010709
TI - Medical devices; gastroenterology and urology devices; classification of the
electrogastrography system. Food and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is classifying the electrogastrography
system (EGG) into class II (special controls). The special controls that will
apply to the EGG system are restriction to prescription use, certain labeling
requirements, design requirements, and data collection requirements. The agency
is taking this action in response to a petition submitted under the Federal Food,
Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of
1976, the Safe Medical Devices Act of 1990, and the Food and Drug Administration
Modernization Act of 1997. The agency is classifying the EGG system into class II
(special controls) in order to provide a reasonable assurance of safety and
effectiveness of the device.
PMID- 11010710
TI - Health standards for occupational noise exposure. Mine Safety and Health
Administration (MSHA), Labor. Final rule.
AB - This final comprehensive rule replaces MSHA's existing standards for occupational
noise exposure in coal mines and metal and nonmetal mines. The final rule
establishes uniform requirements to protect the Nation's miners from occupational
noise-induced hearing loss. The rule is derived in part from existing MSHA noise
standards, and from the Department of Labor's existing occupational noise
exposure standard for general industry promulgated by the Occupational Safety and
Health Administration (OSHA). As a result of the Agency's ongoing review of its
safety and health standards, MSHA determined that its existing noise standards,
which are more than twenty years old, do not adequately protect miners from
occupational noise-induced hearing loss. A significant risk to miners of material
impairment of health from workplace exposure to noise over a working lifetime
exists when miners' exposure exceeds an 8-hour time-weighted average (TWA8) of 85
dBA. MSHA expects that the final rule will significantly reduce the risk of
material impairment within the mining industry as a whole.
PMID- 11010711
TI - Recent trends in children's health insurance coverage: no gains for low-income
children.
AB - The percentage of low-income children who have health insurance has not changed
over the last few years, despite expansions in public coverage through Medicaid
and the State Children's Health Insurance Program (SCHIP). Data from 1996-1997
and 1998-1999 from the Center for Studying Health System Change (HSC) find that
while the proportion of low-income children with public coverage has increased,
the percentage with private insurance coverage has decreased sharply, resulting
in no net change in the percentage who are uninsured. This Issue Brief describes
these recent changes in public and private coverage. Possible factors that may
explain these changes are discussed, including increases in private insurance
premiums, substitution of public for private coverage and changes in the
characteristics of low-income persons. The study did not determine conclusively
the causes of the changes in coverage.
PMID- 11010712
TI - Waging a war on drugs: administering a lethal dose to Kendra's law.
PMID- 11010713
TI - State child health; State Children's Health Insurance Program allotments and
payments to states. Health Care Financing Administration (HCFA), HHS. Final rule.
AB - This rule sets forth the methodologies and procedures to determine the allotments
of Federal funds for each Federal fiscal year (FY) available to individual
States, Commonwealths and Territories under title XXI of the Social Security Act.
This rule also specifies the allotment, payment, and grant award process that
will be used for the States, the Commonwealths and Territories to claim and
receive Federal financial participation (FFP) for expenditures under the State
Children's Health Insurance Program (SCHIP) and related Medicaid program
provisions. Established by section 4901 of the Balanced Budget Act of 1997
(Public Law 105-33), amended by technical amendments (made by Public Law 105
100), and most recently amended by the Medicare, Medicaid and SCHIP Balanced
Budget Refinement Act (BBRA) of 1999 (Public Law 106-113, enacted November 29,
1999), the State Children's Health Insurance Program provides Federal matching
funds to States to initiate and expand health insurance coverage to uninsured,
low-income children. Aggregate Federal funding is limited to a fixed amount for
each Federal fiscal year. This aggregate amount is divided into allotments for
each State. State allotments are determined based on a statutory formula that
divides the total available appropriation among all States with approved child
health plans. Once determined, the amount of a State's allotment for a fiscal
year is available for 3 years. We are publishing this final rule in accordance
with the provisions of sections 2104 and 2105 of the Act that relate to
allotments and payments to States under title XXI.
PMID- 11010714
TI - Addition of medical criteria for evaluating Down syndrome in adults. Social
Security Administration (SSA). Final rule.
AB - We are adding a new listing to evaluate non-mosaic Down syndrome in adults. Our
current regulations only include a listing for evaluating Down syndrome in
children; we evaluate claims filed by adults with Down syndrome under other
listings. We are establishing a separate adult listing for this disorder to
acknowledge its lifelong impact and severity. We expect that these final rules
will simplify and expedite our adjudication of claims filed by adults with non
mosaic Down syndrome.
PMID- 11010715
TI - Obstetrical and gynecological devices; classification of female condoms. Food and
Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is classifying the preamendments female
condom intended for contraceptive and prophylactic purposes. Under this rule, the
preamendments female condom is being classified into class III (premarket
approval). This action is being taken under the Federal Food, Drug, and Cosmetic
Act (the act), as amended by the Medical Device Amendments of 1976, the Safe
Medical Devices Act of 1990, and the FDA Modernization Act of 1997.
PMID- 11010716
TI - Hematology.
PMID- 11010717
TI - Radial artery harvesting.
PMID- 11010718
TI - Pharmaceutical marketplace dynamics.
PMID- 11010719
TI - Sterility requirement for aqueous-based drug products for oral inhalation. Food
and Drug Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is amending its regulations to require
that all prescription and over-the-counter (OTC) aqueous-based drug products for
oral inhalation be manufactured sterile. This rule applies to aqueous-based oral
inhalation drug products in both single-dose and multiple-use primary packaging.
Pressurized metered-dose inhalers are not subject to this rule. Based on reports
of adverse drug experiences from contaminated nonsterile inhalation drug products
and recalls of these products, FDA is taking this action to help ensure the
safety and effectiveness of these products.
PMID- 11010720
TI - Nondiscrimination on the basis of disability in air travel; compensation for
damage to wheelchairs and other assistive devices. Office of the Secretary, DOT.
Final rule.
AB - The Department is amending its rules implementing the Air Carrier Access Act of
1986 (ACAA) to lift an existing cap on the amount of compensation airlines have
to pay to passengers for loss or damage of their wheelchairs and other assistive
devices. The rule is intended to provide additional relief to passengers who use
expensive assistive devices that are lost, destroyed or damaged in the course of
airline travel.
PMID- 11010721
TI - Federal Employees Health Benefits (FEHB) Program and Department of Defense (DoD)
demonstration project. Office of Personnel Management. Final rule.
AB - OPM is issuing a final regulation to implement the portion of the National
Defense Authorization Act for 1999 that establishes authority for a demonstration
project under which certain Medicare and other eligible DoD beneficiaries can
enroll in health benefit plans in certain geographic areas under the Federal
Employees Health Benefits (FEHB) Program. The demonstration project will run for
a period of three years from January 1, 2000, through December 31, 2002. This
regulation specifies only the requirements that differ from existing FEHB Program
regulations because of unique aspects of the demonstration project.
PMID- 11010722
TI - Children suffering from spina bifida who are children of Vietnam veterans.
Department of Veterans Affairs. Final rule.
AB - This document amends Department of Veterans Affairs (VA) regulations concerning
benefits for children suffering from spina bifida who are children of Vietnam
veterans. This is necessary to implement statutory changes contained in the
Veterans' Benefits Act of 1997.
PMID- 11010723
TI - The State Vocational Rehabilitation Services Program. Office of Special Education
and Rehabilitative Services, Department of Education. Final regulations.
AB - The Secretary amends the regulations governing The State Vocational
Rehabilitation Services Program (VR program). These amendments are needed to
implement changes in the Rehabilitation Act of 1973, as amended (Act). These
changes establish evaluation standards and performance indicators for the VR
program.
PMID- 11010724
TI - Privacy Act; implementation. Office of Inspector General (OIG), HHS. Final rule.
AB - This final rule exempts the new system of records, the Healthcare Integrity and
Protection Data Bank (HIPDB), from certain provisions of the Privacy Act (5
U.S.C. 552a). The establishment of the HIPDB is required by section 1128E of the
Social Security Act (the Act), as added by section 221(a) of the Health Insurance
Portability and Accountability Act (HIPAA) of 1996. Section 1128E of the Act
directed the Secretary to establish a national health care fraud and abuse data
collection program for the reporting and disclosing of certain final adverse
actions taken against health care providers, suppliers or practitioners, and to
maintain a data base of final adverse actions taken against health care
providers, suppliers and practitioners. Regulations implementing the new HIPDB
were published in the Federal Register on October 26, 1999 (64 FR 57740). The
exemption being set forth in this rule applies to investigative materials
compiled for law enforcement purposes.
PMID- 11010725
TI - Medicare program; State Health Insurance Assistance Program (SHIP). Health Care
Financing Administration (HCFA), HHS. Interim final rule with comment period.
AB - This interim final rule explains the terms and conditions that apply to grants to
States for counseling and assistance to Medicare beneficiaries, and makes several
minor technical clarifications about program compliance. We also specify our
policies regarding the treatment of funds associated with the management of this
program, including user fee assessments not in effect when prior regulations were
issued. This interim final rule is issued in accordance with section 4360 of the
Omnibus Budget Reconciliation Act of 1990 (OBRA '90) and section 1857(e)(2) of
the Social Security Act (the Act).
PMID- 11010726
TI - Investigational new drug applications; amendment to clinical hold regulations for
products intended for life-threatening diseases and conditions. Food and Drug
Administration, HHS. Final rule.
AB - The Food and Drug Administration (FDA) is amending the regulations governing
investigational new drug applications (IND's) to permit FDA to place a clinical
hold on one or more studies under an IND involving a drug that is intended to
treat a life-threatening disease or condition affecting both genders. The
amendments permit the agency to place a clinical hold on such studies if men or
women with reproductive potential who have the disease or condition are otherwise
eligible but are categorically excluded from participation solely because of a
perceived risk or potential risk of reproductive or developmental toxicity from
use of the investigational drug. This rule was developed in response to the past
practice of excluding women with reproductive potential from early clinical
trials because of a perceived risk or potential risk of reproductive or
developmental toxicity. The final rule does not impose requirements to enroll or
recruit a specific number of men or women with reproductive potential.
PMID- 11010727
TI - Federal old-age, survivors and disability insurance and Supplemental Security
Income for the Aged, Blind, and Disabled; medical and other evidence of your
impairment(s) and definition of medical consultant. Social Security
Administration. Final rules.
AB - We are revising the Social Security and Supplemental Security Income (SSI)
disability regulations regarding sources of evidence for establishing the
existence of a medically determinable impairment under title II and title XVI of
the Social Security Act (the Act). We are doing this to clarify and expand the
list of acceptable medical sources and to revise the definition of the term
"medical consultant" to include additional acceptable medical sources.
PMID- 11010728
TI - Managed long-term care: what role do Area Agencies on Aging play?
PMID- 11010729
TI - Beyond 43 million: the "regarded as" prong of the ADA and HIV infection--a
tautological approach.
PMID- 11010730
TI - Effects of a program of intervention on parental distress following infant death.
AB - A longitudinal study of 144 parents (65 fathers, 79 mothers) was conducted to
evaluate the effectiveness of a program of intervention in relieving the
psychological distress of parents affected by infant death. Participants were
assessed in terms of their psychiatric disturbance, depression, anxiety, physical
symptoms, dyadic adjustment, and coping strategies. The experimental group (n =
84) was offered an intervention program comprising the use of specially designed
resources and contact with a trained grief worker. A control group (n = 60) was
given routine community care. Parental reactions were assessed at four to six
weeks postloss (prior to the implementation of the intervention program), at six
months postloss, and at 15 months postloss. A series of multivariate analyses of
variance revealed that the intervention was effective in reducing the distress of
parents, particularly those assessed prior to the intervention as being at high
risk of developing mourning difficulties. Effects of the intervention were noted
in terms of parents' overall psychiatric disturbance, marital quality, and
paternal coping strategies.
PMID- 11010731
TI - The do-not-resuscitate decision: the context, process, and consequences of DNR
orders.
AB - This study examines the process and consequences of an increasingly important
element of the dying experience in American hospitals: the writing of a Do-Not
Resuscitate (DNR) order. The focus of the study is on the decision-making process
and timing of the DNR decision, the impact of the DNR order on the dying
experience, and the consequences of the DNR order for length of hospital stay and
accrued medical charges. Patients with a DNR order are compared to those who were
unsuccessfully coded. Data are obtained from a review and analysis of the medical
charts and death monitor sheets of a sample of 249 persons who died in 1994 in a
single teaching hospital. The study found physicians routinely discuss the DNR
decision with patients and/or their surrogates (though patients are involved in
the decision in only about one-third of cases) and that the decision is often
made relatively early in the hospital stay. The dying experience of patients with
a written DNR was different in significant ways from the experience of
unsuccessfully-coded patients. Those with a DNR were more likely to remain in a
single unit in the hospital and less likely to die in an intensive care unit or
while connected to a ventilator. Consistent with other studies, however, average
length of hospital stay and average medical charges were actually higher for the
DNR patients. Implications of these differences between DNR and unsuccessfully
coded patients are discussed.
PMID- 11010732
TI - Death education: knowledge, attitudes, and perspectives of Irish parents and
teachers.
AB - This article reports on a cross-sectional survey of the knowledge, attitudes and
perspectives of Irish parents and school teachers concerning children's grief and
the concept of death education. The sample comprised 119 parents and 142 teachers
of Irish Primary-school children (5-12 years of age) who completed a self
administered questionnaire. Both parents and teachers reported high levels of
understanding of the nature of children's grief and strongly supported the view
that death should be discussed with children before they encounter it. Although
discussions of death were reported in the classroom and in the home, both
teachers and parents, particularly men, reported being uncomfortable talking to
children about death. There was general support for inclusion of death education
in the school curriculum, with both teachers and parents supporting the need for
further teacher training to undertake its delivery. There were few significant
differences between the expressed attitudes of parents and teachers. However,
teachers were more likely than parents to agree that death education would take
away from parental responsibility. The implications of the findings for further
work in this area are considered.
PMID- 11010733
TI - Death experiences and hospice: perceptions of college students.
AB - The purpose of this study was to investigate college-age students' awareness of
and involvement in hospice and to ascertain information regarding their own
experiences with death and their preferences about death and dying. Our data were
gathered through a mailed survey to 521 biology majors at an undergraduate
college in the southeastern United States (122 responded or 23%). The majority of
respondents were aware of hospice, yet less than 25% had any involvement with
hospice. Over 90% of the respondents had seen a dead body, and one-third had
witnessed a death. Statistically significant differences by gender were found
only with awareness of hospice, with women being more knowledgeable. With health
professions as the goal for most of these students, a similar study with a cohort
of non-college students, or even non-health-profession-bound college students,
would serve as an interesting "control" group.
PMID- 11010734
TI - Federal Employees Health Benefits (FEHB) program and Department of Defense (DoD)
demonstration project; and other miscellaneous changes. Office of Personnel
Management. Final rule.
AB - OPM is issuing a final regulation to implement the portion of the Defense
Authorization Act for 1999 that establishes authority for a demonstration project
under which certain Medicare and other eligible DoD beneficiaries can enroll in
health benefit plans in certain geographic areas under the Federal Employees
Health Benefits (FEHB) Program. The demonstration project will run for a period
of three years from January 1, 2000, through December 31, 2002. This regulation
specifies only the requirements that differ from existing FEHB Program
regulations because of unique aspects of the demonstration project. This
regulation also makes other miscellaneous changes to the Federal Employees Health
Benefits Acquisition Regulations.
PMID- 11010735
TI - Privacy Act of 1974; proposed implementation. Office of the Secretary, HHS. Final
rule.
AB - The Department of Health and Human Services is exempting a new system of records,
09-25-0213, "Administration: Investigative Records, HHS/NIH/OM/OA/OMA," from
certain requirements of the Privacy Act to protect records compiled in the course
of an inquiry and/or investigation and to protect the identity of confidential
sources who furnish information to the Government under an express promise that
the identity of such source would be held in confidence.
PMID- 11010736
TI - Sick leave for family care purposes. Office of Personnel Management. Final rule.
AB - The Office of Personnel Management is issuing final regulations to expand the use
of sick leave for family care purposes. Under the final regulations, an employee
may use a total of up to 12 weeks of accrued sick leave each year to care for a
family member with a serious health condition. This benefit broadens the options
available for employees to meet their family responsibilities.
PMID- 11010737
TI - HCFA's outpatient PPS: finally ready to roll?
PMID- 11010738
TI - Name brands: the effects of intrusive HIV legislation on high-risk demographic
groups.
PMID- 11010739
TI - Confusion in the courts: managed care financial structures and their impact on
medical care.
PMID- 11010740
TI - Abacavir: new preparation. Risks limit the value.
AB - (1) Abacavir, a nucleoside inhibitor of HIV reverse transcriptase, is indicated
for the treatment of HIV-infected adults, in combination with other
antiretroviral drugs. (2) The assessment file is limited mainly to trials
involving patients who have never received other antiretroviral drugs. There are
no comparisons of abacavir plus two other nucleoside inhibitors versus three
nucleoside inhibitors or versus one non nucleoside inhibitor plus two nucleoside
inhibitors. (3) According to initial results the optimal dose regimen of
abacavir in adults appears to be 300 mg twice a day. The lamivudine + zidovudine
+ abacavir combination reduces viral load more strongly than the lamivudine +
zidovudine combination in patients not previously treated with antiretroviral
drugs. Preliminary results suggest that the same applies to patients previously
treated with antiretroviral drugs. (4) A trial involving 562 previously
untreated patients showed that the effect of the abacavir + lamivudine +
zidovudine combination (total of 4 tablets a day) was not significantly different
from that of the indinavir + lamivudine + zidovudine combination (8 tablets a
day) after 48 weeks of treatment. (5) In clinical trials, approximately 3% of
adults and 5% of children had hypersensitivity reactions to abacavir. Under the
strict conditions of the trials it was not always possible to avoid abacavir
rechallenge, which carries a risk of a new, potentially fatal hypersensitivity
reaction. (6) The risk-benefit ratio of abacavir is currently unfavourable in
children, who must not be prescribed the drug. (7) The risk of drug interactions
with abacavir is low.
PMID- 11010741
TI - Alendronic acid in primary prevention: new indication. No reduction in fracture
risk.
AB - (1) Alendronic acid at a dose of 5 mg/day is now licensed in France for primary
prevention of postmenopausal fractures. (2) The clinical file is relatively
bulky and methodologically adequate, but there are no comparisons with combined
hormone replacement therapy or with raloxifen. (3) Three trials have shown that
5 mg/day alendronic acid slows postmenopausal bone loss. However, this effect
disappears on treatment cessation, and mineral bone density is only one risk
factor for postmenopausal fractures. (4) A placebo-controlled trial of primary
prevention involving more than 4,000 patients showed no reduction in the risk of
fracture after 4 years of treatment with alendronic acid (5 mg/day for 2 years,
then 10 mg/day). (5) Alendronic acid increases the risk of oesophageal
ulceration, necessitating strict precautions during ingestion.
PMID- 11010742
TI - Ribavirin: new preparation. An advance, but still no cure-all.
AB - (1) Ribavirin is licensed for patients with hepatitis C who have not been treated
previously or who have relapsed. According to the licence, ribavirin must be
combined with interferon alfa-2b. (2) The clinical file is bulky and of
acceptable methodological quality. (3) Some trials have shown that ribavirin
monotherapy has no effect on viral load. Two trials involving patients who had
relapsed after transaminase normalisation on interferon alfa-2b monotherapy show
that the ribavirin + interferon alfa-2b combination is more effective than
interferon alfa-2b alone in rendering viraemia undetectable and normalising
transaminase activity for at least 6 months after treatment cessation. (4) A
trial of patients resistant to interferon alfa monotherapy showed that it was
more beneficial to combine ribavirin + interferon alfa-2b than to double the dose
of interferon alfa-2b alone, in terms of driving viraemia below the detection
limit and persistently normalising transaminase activity. (5) Three trials
involving patients who had not been treated previously showed that the ribavirin
+ interferon alfa-2b combination was more effective than interferon alfa-2b
monotherapy in driving viraemia below the detection limit for at least 6 months
after treatment cessation, and in reducing the liver inflammation score. No
effect on fibrosis or on the risk of cirrhosis has yet been demonstrated. (6)
The best duration of treatment is not known, but seems to depend on prognostic
factors. The following factors might permit shorter treatment: relatively low
viral load, early-stage fibrosis, female sex, age below 40 years, and infection
by genotype 2 or 3 strains. (7) The ribavirin + interferon alfa-2b combination
causes haemolytic anaemia in most patients, and this can be severe. (8)
Ribavirin is teratogenic and causes sperm defects.
PMID- 11010743
TI - Goserelin and locally advanced prostate cancer: new indication. Pros and cons.
AB - (1) Goserelin, a GnRH agonist, has a new licensed indication in France, as an
adjuvant to external radiotherapy for locally advanced prosate cancer. (2) The
clinical file in this indication includes two trials of satisfactory
methodological quality comparing radiotherapy + goserelin with radiotherapy
alone. (3) In these trials the radiotherapy + goserelin combination increased
the specific-symptom-free survival time. (4) In one trial goserelin caused
endocrine disorders in 19% of patients. There were also more cases of urinary
incontinence (13% in absolute values) among patients receiving the radiotherapy +
goserelin combination. Furthermore, goserelin almost always causes impotence and
reduced libido.
PMID- 11010744
TI - Lidocaine + prilocaine before 3 months of age: new indication. Correct use is
crucial.
AB - (1) The lidocaine + prilocaine combination, as a cream or adhesive dressings, is
now approved for anaesthesia of healthy skin in children of 0 to 3 months, an age
range in which it used to be contraindicated. (2) The clinical file on the
lidocaine + prilocaine combination in this age range is of acceptable
methodological quality. (3) For circumcision, two trials showed that the
lidocaine + prilocaine cream was more effective than a placebo cream in
preventing pain. Two other trials showed that the lidocaine + prilocaine cream
was less effective than penile block or local anaesthetic injection in newborns.
(4) During heel blood sampling in newborns, the two available comparative trials
showed no analgesic efficacy of the lidocaine + prilocaine combination. However,
heel blood sampling is an unnecessary procedure. (5) The two comparative trials
involving venepuncture in newborns showed, at best, a moderate analgesic effect
of the lidocaine + prilocaine combination. (6) Cases of symptomatic
methaemoglobinaemia have occurred when recommended conditions of use are not
observed.
PMID- 11010745
TI - Dexamethasone misused for weight gain.
PMID- 11010746
TI - Bronchospasm with zanamivir.
PMID- 11010747
TI - Antiplatelet drugs in cardiovascular prevention: introduction.
PMID- 11010748
TI - Antiplatelet drugs in cardiovascular prevention: take adverse effects and costs
into account.
AB - (1) Several antiplatelet drugs have proven preventive efficacy, including
aspirin, aspirin + dipyridamole, clopidogrel, ticlopidine and flurbiprofen. They
differ mainly in their adverse effects and costs. (2) Aspirin has essentially
gastrointestinal adverse effects, whose incidence can be limited by prescribing a
daily dose below 350 mg. (3) The addition of dipyridamole to aspirin can cause
headache and diarrhoea. (4) Ticlopidine should be avoided because of the risk of
agranulocytosis. (5) Adverse effects are less frequent and less severe with
clopidogrel than with ticlopidine. (6) Like other nonsteroidal antiinflammatory
drugs, flurbiprofen has mainly gastrointestinal adverse effects. (7) Treatment
is least costly with low-dose aspirin and most costly with clopidogrel.
PMID- 11010749
TI - Antiplatelet drugs in cardiovascular prevention: coronary events: acute phase and
secondary prevention.
AB - (1) Aspirin reduces acute-phase mortality after myocardial infarction, and also
reduces the risk of myocardial infarction and death in patients with unstable
angina. Aspirin reduces the risk of myocardial infarction in patients with stable
angina and after unstable angina, and the risk of relapse after myocardial
infarction. It reduces the risk of complications during coronary angioplasty, and
the risk of venous coronary bypass graft occlusion after coronary surgery. (2)
The best risk-benefit ratio with aspirin is achieved at a daily dose of 75-350
mg; 160 mg/day is the best-validated dose in the acute phase of myocardial
infarction. (3) Aspirin must be combined with a thrombolytic agent in patients
with myocardial infarction, and with heparin in patients with unstable angina.
During coronary stenting the aspirin + clopidogrel combination may have a better
risk-benefit ratio than the aspirin + ticlopidine combination. (4) Clopidogrel
can be used when aspirin is contraindicated or poorly tolerated. (5) Oral
anticoagulants seem a better option than aspirin after complicated myocardial
infarction.
PMID- 11010750
TI - Antiplatelet drugs in cardiovascular prevention: stroke: acute phase and
secondary prevention.
AB - (1) In the acute phase of ischaemic stroke in patients free of thrombogenic heart
disease, combined treatment with aspirin + moderate-dose unfractionated heparin
reduces the risk of relapse and death. Unfractionated heparin at higher
anticoagulant doses has an unfavourable risk-benefit ratio. Treatment is
controversial in patients with events associated with atrial fibrillation. (2)
After ischaemic stroke in patients free of thrombogenic heart disease, aspirin
reduces the risk of relapse and death. Other antiplatelet drugs, the aspirin +
dipyridamole combination, ticlopidine and clopidogrel have similar efficacy to
aspirin. (3) The risk-benefit ratio of oral anticoagulant is favourable after
ischaemic stroke associated with atrial fibrillation; but it is unfavourable
after stroke without thrombogenic heart disease.
PMID- 11010751
TI - Antiplatelet drugs in cardiovascular prevention: stroke prevention in patients
with thrombogenic heart disease.
AB - (1) In patients with atrial fibrillation and a moderate embolic risk, aspirin
reduces the risk of stroke and has a comparable risk-benefit ratio to oral
anticoagulants. (2) Oral anticoagulants are superior to aspirin in patients with
atrial fibrillation and a history of stroke. (3) In patients with a mechanical
valve prosthesis and a high embolic risk, the oral anticoagulant + aspirin
combination has a better risk-benefit ratio than oral anticoagulant alone.
PMID- 11010752
TI - Antiplatelet drugs in cardiovascular prevention: coronary events and stroke:
primary prevention.
AB - (1) Aspirin reduces the risk of myocardial infarction in men over 40 with no
history of cardiovascular disease, and in hypertensive patients of both sexes
over that age. But it does not seem to reduce overall mortality, and its risk
benefit ratio is not very favourable because of its gastrointestinal adverse
effects. (2) In patients with symptomatic lower-limb arterial disease,
ticlopidine and clopidogrel reduce the risk of coronary events.
PMID- 11010753
TI - Prevention of mother-child HIV transmission: progress and problems.
AB - (1) Since 1994, zidovudine administration to pregnant women and their newborns
has been the reference prophylaxis for mother-child HIV transmission. (2) Three
trials done in Thailand and Africa show that zidovudine therapy during the last
few weeks of pregnancy reduces the risk of transmission, especially when breast
feeding is avoided. (3) A retrospective study done in the United States suggests
that even very late zidovudine administration may benefit the mother and/or her
child. (4) A trial done in Uganda suggests that a single dose of nevirapine has
better preventive activity than a very short course of zidovudine in women who
breastfeed. (5) There are very few data on the risk-benefit ratio of multidrug
antiretroviral regimens in pregnant women. (6) Eight cases of mitochondrial
involvement have been diagnosed in France in children exposed to zidovudine or to
the zidovudine + lamivudine combination. These cases call for long-term close
monitoring of children exposed to antiretroviral drugs in utero. To limit the
duration of fetal exposure, the third trimester of pregnancy is now recommended
as the safest time to start antiretroviral prophylaxis. (7) Despite a randomised
trial and a meta-analysis suggesting that elective caesarean section prevents
mother-child HIV transmission, the value of such surgery remains controversial.
PMID- 11010754
TI - Delicate operations.
PMID- 11010755
TI - Out-of-pocket spending on health care by Medicare beneficiaries age 65 and older:
1999 projections.
PMID- 11010756
TI - Medicare beneficiaries and prescription drug coverage: gaps and barriers.
PMID- 11010757
TI - Care management: policy considerations for original Medicare.
PMID- 11010758
TI - Social Security reform: economic effects of planned changes in the CPI.
PMID- 11010759
TI - Medical error and patient injury: costly and often preventable.
PMID- 11010760
TI - Social Security reform: how do minorities fare under Social Security? A response
to two Heritage Foundation reports.
PMID- 11010761
TI - Social Security reform: the Thrift Savings Plan (TSP) for federal employees.
PMID- 11010762
TI - Determining comparable levels of functional disability.
PMID- 11010763
TI - A critical look at equity investment in the 1994-1996 Advisory Council on Social
Security recommendations.
PMID- 11010764
TI - Consumer-directed long-term care: participants' experiences in five countries.
PMID- 11010765
TI - Social Security reform: rethinking retirement-age policy--a look at raising
Social Security's retirement age.
PMID- 11010766
TI - Fractures of the mandibular condyle. Part 1: patterns of distribution of types
and causes of fractures in 348 patients.
AB - This prospective study was designed to record relevant characteristics of
mandibular condyle fractures and to evaluate the relationship between these. Data
were recorded on sex, age, cause of trauma, level of fracture, dislocation of the
mandibular head, dental state and associated fractures of all patients diagnosed
in our hospital during the period 1984-1996 with mandibular condyle fractures.
Data were analysed in our Computer Department. The sample comprised 348 patients
with 444 fractures, and a male:female ratio of 2:1. Traffic accidents were the
most common cause: 103 (41%) of the unilateral and 54 (56%) of the bilateral
fractures, followed by alleged assault and falls. Low fractures were the most
common -n = 314 of 444 (71%). The causes that involved considerable force
(traffic accidents and falls) resulted in more dislocations of the mandibular
head, more bilateral fractures, a tendency to fractures higher on the condyle and
significantly more intracapsular fractures. Absence of molar occlusion also gave
more high and fewer low fractures, but played no part in dislocation of the
mandibular head from the glenoid fossa.
PMID- 11010767
TI - Fractures of the mandibular condyle. Part 2: results of treatment of 348
patients.
AB - This study was designed to record the results of conservative treatment of
condylar fractures and to find out if there were any variables that were
predictive of complications. Data were analysed in our computer department.
During the period 1984-1996, all patients who presented with a fracture of the
mandibular condyle and who attended for control examination one year after
treatment were recorded at the end of treatment and one year later. The ability
to open the mouth, deviation and occlusion were recorded. After one year 45 of
the 348 patients (13%) had minor physical complaints such as reduced ability to
open the mouth, deviation, or dysfunction. Ten of them (3%) had pain in the joint
or muscles or both. Eight patients (2%) had malocclusion, which in seven could be
related to dislocation of the condylar head out of the fossa. Five of the eight
patients had had bilateral fractures. We conclude that conservative treatment of
condylar fractures is non-traumatic, safe, and reliable and in only a few cases
may cause disturbances of function and malocclusion. The risk associated with the
latter is greatest with bilateral fractures and dislocation of the condylar head
from the fossa.
PMID- 11010768
TI - An investigation into the relationship between mandibular third molars and angle
fractures in Nigerians.
AB - We examined the relationship between the presence or absence of mandibular third
molars and angle fractures in Nigerians between January 1976 and July 1997.
Information was obtained from patients' case records and radiographs.A total of
490 patients were seen during the study period, 408 of whom (83%) had their third
molars present, and 76 of whom had angle fractures. Road traffic accidents (n
=304, 62%) were the main cause of the fractures. Of these, 44 (14%) had angle
fractures compared with 14/75 (19%) patients in whom the mechanism of injury was
a fight or assault.Sixty-five of the 408 patients whose third molars were present
(16%) had angle fractures, as did 11/82 (13%) who did not have third molars (p
=0.57). Of the 77 patients whose lower third molars were not erupted, 24 (31%)
had angle fractures compared with 52/331 (16%) in whom the lower third molars
were erupted (p =0.002). These findings suggest that angle fractures are uncommon
in this population because of their particular mechanism of injury. In addition,
the presence of a lower third molar does not necessarily predispose to fractures
of the angle of the mandible. However, angle fractures are more likely to occur
in people with unerupted lower third molars than in those in whom they have
erupted.
PMID- 11010769
TI - Ultrasound and fine needle aspiration cytology in the staging of neck lymph nodes
in oral squamous cell carcinoma.
AB - We prospectively studied 49 patients with oral squamous cell carcinoma (SCC) who
had their cervical regional lymph nodes examined by ultrasound (US), with or
without fine needle aspiration cytology (FNAC), for the detection of metastatic
spread. They were screened over a two-year period (1993-1995) by computed
tomography (CT) and magnetic resonance imaging (MRI) or both to measure the
primary tumour. US, with or without FNAC, was used to stage the neck. All tumours
were biopsied preoperatively and the diagnosis of SCC conformed by histological
examination. Management of the neck was based on US staging. Thirty-five patients
had neck dissections and 14 were managed conservatively. Mean follow-up was 30
months (range 24-48). All patients were alive at one year, but one died at 14
months from recurrence of disease in the neck. There were 3 false negatives (6%).
We find that US, with or without FNAC, is an accurate (86%), sensitive (92%) and
specific (83%) technique for the preoperative assessment of lymph node metastases
in patients with SCC.
PMID- 11010770
TI - Quantitative volume replacement in the correction of post-traumatic enophthalmos.
AB - We describe a technique to correct enophthalmos that involves measurement of the
volume of the injured orbit followed by an accurate replacement of this volume
with an autogenous bone graft. Twelve consecutive patients were treated with this
technique and all but one showed an improvement in enophthalmos. Four of the
seven with diplopia improved after the operation.
PMID- 11010771
TI - The bicoronal flap (craniofacial access): an audit of morbidity and a proposed
surgical modification in male pattern baldness.
AB - Maxillofacial surgeons have used the bicoronal flap for nearly three decades to
gain access to the craniofacial skeleton. A retrospective analysis of 68
bicoronal flaps done over a five-year period showed that our incidence of
permanent morbidity was low. Although 24 patients (35%) experienced some form of
sensory abnormality immediately after the operation, this persisted for longer
than two years in only one. Complete motor recovery occurred by one year in all
15 patients (22%) who developed postoperative frontalis weakness. Three patients
developed male pattern baldness postoperatively, which resulted in exposure of
the scar and poor cosmesis. This prompted a cadaveric study in which we assessed
the feasibility of modifying the position of the standard bicoronal incision in
people who are prone to hair loss. The pivotal point of the bicoronal flap was
found to lie at its most inferior aspect. By extending the incision into the skin
crease in front of the lobe of the ear it was possible to adjust the
anteroposterior position of the bicoronal incision without limiting access to the
facial skeleton. We therefore advocate occipitally placed incisions with
preauricular extensions in patients who are prone to male pattern baldness.
PMID- 11010772
TI - Incidence of human papillomavirus 16 and 18 infection and p53 mutation in
patients with oral squamous cell carcinoma in Japan.
AB - The purpose of this study was to investigate the prevalence of human
papillomaviruses (HPVs) 16 and 18 infection, and p53 mutation in oral squamous
cell carcinomas (SCCs) in Japanese patients. Our results showed a higher
incidence of HPV16 and 18 infections than previous studies because we combined
the findings of a consensus polymerase chain reaction (PCR), restriction fragment
length polymorphism by using the restriction enzyme digestion of the PCR products
and Southern blot hybridization. Each HPV16 and 18 E6/E7 DNA was detected in 9
(20%) and 25 (54%) of 46 samples. The p53 mutation in the exons from 5 to 8 were
detected in 20 out of 46 samples (43%) by a PCR-single strand conformation
polymorphism analysis. There was a significant relationship between HPV16 and the
p53 mutation (P =0.02) suggesting that HPV16 infection has a mutagenic effect in
oral SCC. However, neither HPV infection nor p53 mutation influenced survival.
PMID- 11010773
TI - Grey-scale sonography in assessment of cervical lymphadenopathy: review of
sonographic appearances and features that may help a beginner.
AB - Ultrasound examinations of the neck in 218 patients with confirmed cervical
lymphadenopathy were reviewed. Lymph nodes were assessed for their size, shape,
internal architecture, echogenicity, nodal border, posterior enhancement, and
ancillary features (adjacent soft tissues oedema, and matting). The hilus is a
linear, echogenic, non-shadowing structure containing nodal vessels, and is
continuous with fat around the node. Coagulation necrosis is an ill-defined,
rounded, non-shadowing echogenic area within a node. It is less echogenic than
the hilus and is not continuous with the fat around the node. Calcification is a
highly echogenic focus within the node, which may be dense or punctate echogenic
foci. It is not continuous with the fat around the node. Dense intranodal
calcification usually produces shadowing. However, fine punctate calcification
may not have posterior shadowing though, if the transducer frequency is
increased, it may show thin lines. Cystic necrosis is focal, often ill-defined
echolucent area within the node. Echogenicity of lymph nodes is usually compared
with the adjacent muscles, and is classified as hypoechogenicity,
isoechogenicity, and hyperechogenicity. The nodal border is assessed for its
sharpness. Posterior enhancement is when the structures posterior to the node
look more echogenic than neighbouring areas. Oedema of soft tissues is an ill
defined, hypoechoic area around the node with loss of adjacent fascial planes.
Nodes are considered matted when they are clumped or adherent to each other with
no normal intervening soft tissue between them. Ultrasound features that help
only in identifying abnormal nodes include size, shape, echogenic hilus,
hypoechogenicity or isoechogenicity, echogeneity, coagulation necrosis, and a
sharp nodal border. Ultrasound features that help to identify abnormal nodes as
well as giving clues to the primary lesion include hyperechogenicity, intranodal
calcification, intranodal cystic necrosis, ragged nodal border, posterior
enhancement, adjacent soft tissue oedema, and matting.
PMID- 11010774
TI - Tumour volume estimated by computed tomography as a predictive factor in
carcinoma of the tongue.
AB - This retrospective study evaluated tumour volume, estimated by computed
tomography (CT), as a predictive factor in carcinoma of the tongue. Tumour volume
was measured from pretreatment CT scans of 20 consecutive patients, followed up
for at least 3 years, and this measurement was compared with tumour volume
estimated from pathological specimens. T-stage and CT-derived tumour volume were
compared with the clinical and pathological status of the nodes, and with the
outcome of treatment. The measurement of tumour volume derived from CT correlated
well with measurements derived from pathological examination, and tumour volume
also predicted overall treatment failure. The disease-specific survival rate was
100% for patients with low-volume tumours (<13 cc) compared with 79% for those
with stage T1 and T2 tumours.CT is a reliable way of measuring the volume of
tumours in carcinoma of the tongue, and tumour volume is useful adjunct to the
clinical tumour-node-metastases staging system.
PMID- 11010776
TI - Role of surgical reduction of condylar fractures in the management of panfacial
fractures.
AB - We present nine panfacial fractures that were treated during a two-year period in
which the first step in treatment was reduction of condylar fractures. There was
no evidence of dental or skeletal alterations and measurement of the mandibular
ramus and radiographic examination show that posterior facial height as well as
projection and width of the inferior lower third of the face, was restored. The
correct timing of surgical intervention and the use of rigid fixation allows the
restoration of the morphological and functional nature of the face after
panfacial fractures.
PMID- 11010775
TI - Botulinum toxin: new treatment for temporomandibular disorders.
AB - BACKGROUND: Temporomandibular disorders (TMDs) affect the face and jaws, and
cause chronic pain and dysfunction in many people. As in other conditions
involving the musculoskeletal system, controlling the myogenous component is an
integral part of treatment. In this study, we evaluated subjective and objective
responses to treatment with botulinum toxin A (BTX-A) in a group of 46 patients
with TMDs. METHODS: 46 subjects with TMD were enrolled in this uncontrolled study
and treated with BTX-A 150U. Both masseter muscles were injected with 50 U each
and both temporalis muscles with 25 U each under electromyographic guidance.
Subjects were assessed at two-week intervals for eight weeks. Outcome measures
included subjective assessment of pain by visual analogue scale (VAS),
measurement of mean maximum voluntary contraction (MVC), interincisal oral
opening, tenderness to palpation, and a functional index based on multiple VAS.
Medians of the data were taken for each outcome measure at each time point and
subjected to Duncan's multiple range test. RESULTS: There were significant
(P<0.05) differences in all median outcome measures between the pre-treatment
assessment and the four follow-up assessments except for MVC. Although MVC was
significantly reduced midway through the study, it had returned to pretreatment
values by the final two assessments. All other outcome measures remained
significantly different from the pretreatment findings. Paired correlation of
variables including age, sex, diagnosis, depression index, and time of onset
showed no significant differences. CONCLUSIONS: BTX-A injections produced
significant improvements in pain, function, mouth opening, and tenderness to
palpation. MVC initially diminished then returned to the initial values. Although
the study was uncontrolled, the results strongly suggest that BTX-A reduces
severity of symptoms and improves functional abilities for patients with TMD and
that these extend beyond its muscle-relaxing effects.
PMID- 11010777
TI - Staged operations for basal cell carcinoma of the face.
AB - 211 patients (88 female, 123 male, mean age 63 years) presented with 279 basal
cell carcinomas (191 primary tumours, 88 recurrent tumours) in the head and neck
area that were excised. The resected margins were examined microscopically and
the defect repaired at a second operation. The excision margin was 1-2 mm. The
recurrence rate was 3%, which is lower than is achieved by other methods, and
unaffected structures are optimally conserved.
PMID- 11010778
TI - Assessing health outcomes after extraction of third molars: the postoperative
symptom severity (PoSSe) scale.
AB - A postoperative symptom severity (PoSSe) scale was devised from questions
commonly used in the clinical assessment of patients who have had third molars
extracted, and divided into subscales corresponding to seven main adverse effects
that had been identified in a previous study. Ninety-seven patients completed the
15-item questionnaire at one week, and 71 patients at four weeks, after
extraction of impacted third molars. After statistical testing, four items were
discarded and the final PoSSe scale achieved a high level of internal
reliability. Patients' PoSSe scores were highly correlated with scales that
measured six distinct health dimensions. The level of social functioning,
together with the number of impacted teeth and number of painkillers taken,
explained 62% of the variation in PoSSe scores between patients one week
postoperatively. The PoSSe was more responsive than the Short Form 36-item Health
Survey. In conclusion, we found the PoSSe Scale to be a reliable, valid and
responsive measure of the severity of symptoms after extraction of third molars,
and of the impact of those symptoms on patients' perceived health.
PMID- 11010779
TI - Secondary alveolar bone grafting in cleft lip and palate patients.
AB - The case records of 72 patients in Northern Ireland who had secondary bone
grafting of 94 alveolar clefts between 1987 and 1997 were examined. Details were
recorded of age, sex, laterality of cleft, preoperative orthodontic treatment,
whether grafting was combined with soft tissue revision, method of harvesting the
graft, complications, eruption of canines, and the success of grafting as
established by bone levels around the erupted canine. Bone levels were assessed
on a four-point scale. Of 64 canines fully erupted in 94 clefts, 91% achieved
bone levels of Type I or II and only two grafts failed. The outcome was more
favourable when the canine was unerupted preoperatively.
PMID- 11010780
TI - Impact of dedicated trauma lists on a maxillofacial surgical service.
AB - In 1995, the maxillofacial surgical inpatient services in East Lancashire were
centralized in Blackburn Royal Infirmary, and twice-weekly operating lists
dedicated to maxillofacial trauma were established. We examined the non-elective
workload for three-month periods before and after trauma lists became available
to find out the proportion of non-elective operations done out of normal working
hours. Although there was an increase in the total number of non-elective
patients after centralization, day-time trauma lists allowed a reduction in the
proportion of operations performed out of normal working hours. Fewer trauma
cases were added to elective lists. Trauma lists allow the unit to comply with
the recommendations of both NCEPOD and the Calman report, in that they maximize
training opportunities for all staff and facilitate both audit and research.
PMID- 11010781
TI - Isolated orbital blowout fractures: survey and review.
AB - The management of orbital blowout fractures is controversial. The continuing
debate includes the use of antibiotics and steroids, imaging, the surgical
approach, and the choice of implant material for repair of the bony defect.A
cross-sectional study was undertaken to assess current practice in treating
orbital blowout fractures in the UK, in the form of a tick-box questionnaire. The
questionnaire contained 9 closed and 2 open questions, and was forwarded to 256
practising fellows of the British Association of Oral and Maxillofacial Surgery.
The response rate to the questionnaire was 73% (187/256). There was no consensus
about the use of prophylactic antibiotics. However, 91% prescribed post-operative
antibiotics and over half the respondents prescribed steroids. The most common
imaging techniques used were computed tomography (CT, 88%) and plain radiograph
(83%), 60% routinely sought an ophthalmic opinion and 65% assessed visual acuity.
The most common surgical approaches were the subciliary (41%) and the
infraorbital (37%), over half the respondents preferred to operate 6-10 days
after the injury, and silicone elastomer was the preferred implant material of
66%.
PMID- 11010782
TI - Irrigation of the Hall's air drill using a Foley catheter.
PMID- 11010783
TI - Endogenous fatty acid synthesis in squamous cell carcinomas of the oral cavity.
AB - We measured the synthesis of endogenous fatty acids in oral squamous cell
carcinoma, its adjacent tissue, and normal oral tissues that were collected fresh
from surgical specimens. The tissues were minced in Roswell Park Memorial
Institute Medium 1640 (RPMI 1640) and incubated in [1(2)-(14)C] acetic acid,
sodium salt ((14)CH(3)(14)CO(2)Na). Total lipids were then extracted and(14)C was
measured by scintillation counter. We found that incorporation of(14)C in the
total lipids of squamous cell carcinoma was significantly higher than in the
other tissues.
PMID- 11010784
TI - Analysis of tracheostomy-associated morbidity after operations for head and neck
cancer.
AB - Tracheostomy is a safe and effective way of securing the airway in patients who
have radical resections for head and neck cancer. We audited the morbidity after
265 tracheostomies to identify the risks in relation to head and neck surgery,
and to propose recommendations to improve care.Twenty-one tracheostomy-related
complications were encountered in 256 patients (8%). Most complications occurred
during the early postoperative period (72%). There were no tracheostomy-related
deaths.Tracheostomies were retained for a median of 10 days (range 1-160).
Delayed extubation was associated with extent of resection [P = 0.006], site of
tumour (floor of mouth and anterior two thirds of tongue [P = 0.02]), and age
(<61 years [P = 0.02]). Patients who were given preoperative radiotherapy were
significantly more likely to develop a tracheostomy-related complication (P =
0.03). Patients with a tracheostomy complication were more likely to have other
serious complications (P = 0.05) and in these patients there was a risk of
delayed extubation (P = 0.06). We conclude that elective tracheostomy is
essentially event-free, and most complications occur in the ward.
PMID- 11010786
TI - Oral management of patients following oncology treatment: literature review.
AB - Many tumours of the head and neck are treated by clinical oncologists using
radiotherapy. This treatment modality is particularly effective in destroying
rapidly dividing cells, hence its value in cancer treatment. The tissues of the
oral mucosa, the salivary glands and blood vessels can be damaged as the result
of radiotherapy treatment. As a result, patients experience unwanted oral effects
that have both short and long-term implications. The outlook following treatment
for head and neck cancer continues to improve and, as people keep their teeth
into later life, dentists will increasingly be expected to address the oral
problems that patients experience after radiotherapy. The aim of this article is
to review the current literature concerning the implications and management of
these oral implications of cancer treatment.
PMID- 11010785
TI - Swallowing rehabilitation after oro-pharyngeal resection for squamous cell
carcinoma.
AB - The resection of even relatively small tumours that involve the base of tongue
can lead to problems with swallowing. Free tissue transfer has improved the
functional results and reduced the complications of head and neck surgery. The
outcome after ablative operations depends on the site and extent of the
resection, and in cases where the tongue base is involved, swallowing can be
severely impaired. Aspiration in a patient with swallowing difficulties is of
particular concern, however, there is a range of techniques that can be
introduced during videofluoroscopy to reduce or eliminate aspiration. It is
during the rehabilitation phase that procedures and techniques to improve
swallowing and prevent aspiration should be incorporated. The efficacy of
adaptive manoeuvres needs further evaluation, and in this study we aim to assess
the effectiveness of compensatory procedures and therapy techniques (chin tuck
and supraglottic swallow) in eliminating aspiration. We report on a study of the
swallow function of 13 patients following surgical resection of the oropharynx
including the base of tongue. Postoperative assessment by videofluoroscopy was
carried out at 2 weeks, 1 month, 3 months, and 6 months according to a standard
protocol. Subjects were analysed in two groups depending on the degree of
resection of the tongue base resection (less than 1/4,1/4 or more).Patients'
swallowing disorders were related to the extent of the resection and the
consistency of the bolus. Those with involvement of a quarter of the tongue base
or more generally had greater impairment, and radiotherapy tended to exacerbate
these problems. Compensatory procedures and therapy techniques were effective in
50% of patients who aspirated, and tended to be more effective between the one
month and 6 month follow-up in patients with smaller resections.
PMID- 11010787
TI - Assessment of zygomatico-orbital complex fractures using ultrasonography.
AB - Twenty-two patients were referred to the maxillofacial surgical unit for
assessment and management of suspected fractures of the zygomatico-orbital
complex. In each case, both routine plain radiographic and ultrasound
examinations were made. The aim of the study was to investigate the sensitivity
and reliability of ultrasound to detect such fractures. Imaging with ultrasound
was carried out at five areas: the infraorbital margin; lateral wall of the
maxillary sinus; zygomatic arch; frontozygomatic process; and orbital floor. Both
radiographic and ultrasound findings were correlated with the findings at
operation. An overall agreement of 85% between radiographs and ultrasound scans
was found. Ultrasound imaging was most reliable at the lateral wall of the
maxillary sinus, where the sensitivity was 94% and specificity 100%. The positive
predictive value at this area was 100% compared with radiographic findings. We
conclude that ultrasound is a useful tool in imaging facial trauma as an initial
investigation, and can help to reduce the total number of radiographs required
for the diagnosis of fractures of the zygomatico-orbital complex.
PMID- 11010788
TI - Ultracision: the harmonic scalpel and its possible uses in maxillofacial surgery.
AB - We report on the potential uses and benefits of a new development in incisive
technology. The harmonic scalpel uses high-frequency mechanical energy to offer
the surgeon controlled and precise incision and haemostasis. Vessels up to 2 mm
in diameter may be sealed by coaptation with the blade before division. No
special training or precautions are required before using this self-cleaning
device. It produces considerably less smoke or smell than either diathermy or
laser, which reduces the need for instrument exchanges and smoke evacuation. We
think that it will be useful for tongue resections and possibly for neck
dissections.
PMID- 11010789
TI - Hemifacial atrophy with bilateral short roots.
AB - We present a case in which the patient had both bilateral shortening of the
roots, and hemifacial atrophy. As far as we know, this combination has not been
described before.
PMID- 11010790
TI - Amputation neuroma of the great auricular nerve after operations on the parotid
gland.
AB - We found an incidence of 6% (5/81) of traumatic neuroma after section of the
great auricular nerve during operations on the parotid gland. Excision permits
definitive diagnosis, the stump being allowed to retract beneath the belly of the
sternomastoid muscle. However, excision is not always indicated, and the
diagnosis can be made clinically allowing for a more conservative treatment
policy.
PMID- 11010791
TI - Fine needle aspiration biopsy (FNAB) for lesions of the salivary glands.
AB - We examined 112 fine needle aspiration biopsy (FNAB) specimens of salivary glands
(80 parotid and 32 submaxillary) taken between January 1989 and December 1995.
Cytologic diagnoses were compared with the final histological diagnoses of the
surgical specimens. The sensitivity and specificity were 84.8% and 93.7%
respectively, and the accuracy was 91.1%. We conclude that FNAB by itself does
not provide total security because of the high percentage of false-negatives. It
is nevertheless useful when combined with an adequate clinical history,
examination and radiological tests.
PMID- 11010792
TI - Provision and quality assurance for head and neck cancer care.
AB - In 1998, the British Association of Head and Neck Oncologists (BAHNO) published a
report entitled 'Provision and quality assurance for head and neck cancer care in
the United Kingdom. A nationally co-ordinated multidisciplinary approach'. This
document considered, amongst other issues, operational policies for patient care.
We audited three aspects of the care of 73 patients with head and neck cancer
from initial referral to definitive treatment against standards set out in this
report.Fifty-nine patients (81%) were seen within two weeks of initial referral,
the maximum interval proposed by the BAHNO report. In 41 patients (56%), the
diagnosis was confirmed and their treatment plan determined within the further
two-week period suggested in the report. Of the 25 patients who required adjuvant
radiotherapy, only 11 (44%) began treatment within six weeks of their surgical
phase; this represented the greatest variance from the BAHNO recommendations.
These findings highlight the need for units active in the treatment of specific
diseases to audit their activity against available minimum standards in an
attempt to improve the quality of patient care.
PMID- 11010793
TI - Indication for epidural morphine for the relief of intractable pain in advanced
oral cancer: report of four cases.
AB - It can be difficult to manage the pain of advanced oral cancer. We present four
patients in whom epidural morphine was used for intractable pain at primary or
metastatic sites. For pain supplied by the trigeminal or cervical nerve a small
dose of morphine was given through an epidural catheter inserted into the
epidural space through C7-Th1. A favourable clinical response was achieved in
three. In particular, in one patient who was given continuous morphine using a
computerized ambulatory drug delivery system, we achieved excellent efficacy and
stable control of pain. We think that the effect of the epidural morphine was
decreased in the patient who did not respond because he had previously been
treated with high oral doses. The present study confirmed that morphine given
epidurally in small doses has a strong and prolonged analgesic action with less
toxicity than when given orally.
PMID- 11010794
TI - Differential diagnosis of calcium pyrophosphate dihydrate deposition of the
temporomandibular joint.
AB - Calcium pyrophosphate dihydrate (CPPD) deposition disease (pseudogout) of the
temporomandibular joint (TMJ) is rare. It is characterized by the presence of
crystal deposits that are birefringent under polarized light. Although these
crystals are characteristically weakly birefringent, some other crystals such as
those of calcium oxalate, synthetic steroids, and ethylenediaminetetraacetic acid
are also birefringent. The differential diagnosis should therefore be based on a
quantitative analysis of crystals or observation of the crystal structure in
calcified sections. We present a case of CPPD deposition disease of the TMJ and
report on the value of such an analysis to substantiate the diagnosis.
PMID- 11010795
TI - True eminectomy for internal derangement of the temporomandibular joint.
AB - We carried out a prospective study to assess the short- and long-term outcomes of
true eminectomy in 20 consecutive patients with type III or IV anteriorly
displaced discs in whom conventional conservative treatment had failed to resolve
the symptoms. Maximum opening was measured preoperatively, 3-6 months
postoperatively and at one year postoperatively. Each patient filled out a
Mandibular Functional Impairment Questionnaire [MFIQ] and Clinical Dysfunctional
Index both preoperatively and one year postoperatively. Imaging records included
preoperative and one year postoperative orthopantomograph (OPG) and magnetic
resonance imaging (MRI). Maximum mouth opening one year postoperatively had
increased in 95% of patients (range 5-20 mm, mean 12 mm). There was an
improvement in symptoms, using the MFIQ, in 85% of patients. The Clinical
Dysfunctional Index was reduced to Type I in most patients. MRI showed increase
in rotation and translatory movement of the condylar head. We conclude that true
eminectomy may be used to successfully treat type III and type IV anteriorly
displaced discs in patients who have failed to respond to conventional
conservative treatment.
PMID- 11010796
TI - Vascular osteomuscular autograft prefabrication using coral, type I collagen and
recombinant human bone morphogenetic protein-2.
AB - In 20 male Sprague-Dawley rats, 10 pieces of L-shaped coral combined with type I
collagen and recombinant human bone morphogenetic protein-2 (rhBMP-2) and 10
discs (diameter 5 mm) were wrapped in the gracilis muscle, and left pedicled on
the femoral vessels. Untreated coral was buried in muscle at a distant control
site in 4 animals. After 3 weeks, autografts were examined for the shape of new
bone, vascular patency, and induction of bone. In all grafts in viable tissue,
heterotopic bone was formed. The shape of the new bone was the same as that of
the coral, and there was no significant inflammatory reaction. Part of the coral
in the composite was absorbed. Bone was not formed in any of the control sites.
Coral and type 1 collagen are effective as a carrier for BMP to prefabricate
vascular osteomuscular autografts with designed shape. There is a potential
clinical application for BMP to bioengineer microvascular free flaps with
intrinsic skeletal muscle for maxillofacial reconstruction.
PMID- 11010797
TI - Composite autogenous bone and demineralized bone matrices used to repair defects
in the parietal bone of rabbits.
AB - We compared the amount of new bone produced by endochondral and intramembranous
autogenous bone grafts in the presence of demineralized bone matrices (DBMs)
prepared from intramembranous bone (DBM(IM)) or endochondral bone (DBM(EC)).
Thirty-five bone defects were created in the parietal bone of 20 New Zealand
White rabbits. In the experimental groups, 5 defects were grafted with
endochondral bone, 5 with endochondral bone mixed with DBM(IM)) (EC-DBM(IM)), 5
with intramembranous bone mixed with DBM(IM)(IM-DBM(IM)) and 6 with endochondral
bone mixed with DBM(EC)(EC-DBM(EC)). In the control groups, 10 defects were left
alone (passive control) and 4 were grafted with rabbit skin collagen (active
control). They were all killed on day 14 and the defects were prepared for
histological study. Serial sections were cut across the whole defect.
Quantitative analyses were made on 202 sections of the experimental groups by
image analysis. A total of 414%, 708%, and 85% more new bone was formed in
defects grafted with composite EC-DBM(IM), IM-DBM(IM)and EC-DBM(EC),
respectively, than those grafted with endochondral bone alone (P<0.001). No bone
was formed in either passive or active controls. In conclusion, demineralized
bone matrices, particularly those derived from intramembranous bone, have
extremely high osteoinductive properties and greatly improve the integration of
autogenous bone grafts in the skull.
PMID- 11010798
TI - Unilateral temporalis muscle hypertrophy managed with botulinum toxin type A.
PMID- 11010799
TI - First symptom of multifocal skeletal tuberculosis in children.
PMID- 11010800
TI - Re: Kerawala C.J. Oral cancer, smoking and alcohol: the patients' perspective. Br
J Oral Maxillofac Surg 1999; 37: 374-376.
PMID- 11010801
TI - Re: Newton J.P. et al. Masseteric hypertrophy?: preliminary report. Br J Oral
Maxillofac Surg 1999; 37: 405-408.
PMID- 11010802
TI - Third molar surgery.
PMID- 11010803
TI - Caution in use of bicortical intermaxillary fixation screws.
PMID- 11010805
TI - Notch signaling: a dance of proteins changing partners.
PMID- 11010806
TI - Fas-mediated apoptosis of proliferating, transiently growth-arrested, and
senescent normal human fibroblasts.
AB - Previous studies suggest that apoptotic signaling may require proteins that are
critical to cellular proliferation and cell cycle regulation. To further examine
this question, proliferating, transiently growth-arrested, and senescent normal
human fibroblasts were induced to undergo apoptosis in response to two distinct
mediators of apoptosis-Fas (APO-1/CD95) death receptor and staurosporine.
Ligation of the Fas receptor in the presence of cycloheximide or actinomycin D
resulted in apoptosis of proliferating cells, cells transiently growth arrested
by gamma-irradiation or serum starvation (i.e., G(0) arrest), and permanently
growth-arrested senescent fibroblasts. Proliferating and G(0)-arrested cells were
also susceptible to staurosporine-mediated apoptosis. Surprisingly, gamma
irradiated cells did not undergo staurosporine-mediated apoptosis, and remained
viable for a prolonged time. Fas-mediated apoptosis of senescent fibroblasts was
evidenced by chromosome condensation and by activation of caspase-8 and -3,
proteases crucial for the execution of the Fas apoptosis pathway. In addition,
ligation of the Fas receptor in G(0)-arrested cells did not result in the
activation of p34(cdc2) kinase, arguing that activation of this kinase is not
essential in this apoptotic process. From these studies we conclude that
proliferating, transiently growth-arrested, and senescent normal human
fibroblasts are susceptible to apoptotic signals and that apoptosis is not
necessarily dependent upon cell cycle or proliferative state of the cell.
PMID- 11010807
TI - Thrombin inhibits apoptosis of monocytes and plasminogen activator inhibitor 2
(PAI-2) is not responsible for this inhibition.
AB - Plasminogen activator inhibitor 2 (PAI-2) has been shown to inhibit apoptosis in
transfected cells. We have investigated this phenomenon in activated human
monocytes, which are a physiological source of intracellular PAI-2. Apoptosis of
monocytes was rapidly induced by removal of serum, addition of hydrogen peroxide,
or binding of a monoclonal antibody to Fas. Treatment of monocytes with thrombin
or lipopolysaccharide (LPS) inhibited apoptosis of monocytes and also up
regulated intracellular PAI-2. Increased apoptosis was accompanied with increased
activity of caspases 3 and 8. Thrombin or LPS treatment of monocytes decreased
the activity of both caspases, which correlated with protection from apoptosis.
The role for PAI-2 in protection of monocytes from apoptosis was studied.
Monocytes were transfected with antisense oligonucleotides that blocked PAI-2
antigen, and antisense for PAI-2 had no effect on apoptosis of monocytes. No
interaction was evident between PAI-2 and recombinant caspases 3 and 8 in vitro.
PAI-2 was not a substrate for caspases during apoptosis of monocytes, although
some cleavage of recombinant PAI-2 by caspase 3 was evident in vitro. This study
shows that thrombin or LPS protected monocytes from apoptosis and that PAI-2 did
not mediate this inhibitory effect.
PMID- 11010808
TI - Immunoelectron microscopy provides evidence that tumor necrosis factor receptor
associated protein 1 (TRAP-1) is a mitochondrial protein which also localizes at
specific extramitochondrial sites.
AB - The tumor necrosis factor receptor-associated protein 1 (TRAP-1) interacts with a
variety of proteins involved in diverse functions. We have used quantitative
immunogold electron microscopy and biochemical analysis to evaluate the
subcellular distribution of TRAP-1 in rat tissues. Immunofluorescence employing a
polyclonal antibody raised to human recombinant TRAP-1 reveals specific staining
of mitochondria and nuclear region in mammalian cells. Western blot analysis of
purified rat liver mitochondrial subfractions with the TRAP-1 antibody reveals
that the cross-reactive protein (M(r) approximately 80 kDa) is mainly present in
the matrix compartment. Immunogold labeling of rat tissue sections embedded in LR
Gold resin shows strong labeling of mitochondria in all the tissues examined
(viz., liver, heart, pancreas, kidney, spleen, anterior pituitary gland).
Additionally, specific and significant labeling with TRAP-1 antibody was also
observed in certain tissues in a number of nonmitochondrial locations, including
pancreatic zymogen granules, insulin secretory granules, cardiac sarcomeres, and
nuclei of pancreatic and heart cells, and on the cell surface of blood vessel
endothelial cells. Western blot analysis showed that a cross-reactive protein of
similar molecular mass as TRAP-1 is present in purified pancreatic zymogen
granules. Immunogold labeling was prevented in all tissues by preadsorption of
the TRAP-1 antibody with the purified recombinant TRAP-1 protein. These
observations and the fact that TRAP-1 is synthesized with a typical mitochondrial
targeting presequence strongly indicate that TRAP-1 is primarily a mitochondrial
matrix protein. The localization of this protein at specific extramitochondrial
sites raises interesting and fundamental questions regarding the possible
mechanisms by which these proteins are translocated to such sites.
PMID- 11010809
TI - Site-directed mutagenesis and deletion of three phosphorylation sites of
calsequestrin of skeletal muscle sarcoplasmic reticulum. Effects on intracellular
targeting.
AB - Calsequestrin (CS) is segregated to the junctional sarcoplasmic reticulum (jSR)
of skeletal muscle fibers and is responsible for intraluminal Ca(2+) binding. A
chimeric CS-HA1, obtained by adding the nine-amino-acid viral epitope
hemagglutinin (HA1) to the carboxy-terminal of CS and shown to be correctly
segregated to skeletal muscle jSR in vivo (A. Nori, K. A. Nadalini, A. Martini,
R. Rizzuto, A. Villa, and P. Volpe, 1997, Am. J. Physiol. 272, C1420-C1428), is
mutagenized in order to identify domains of CS involved in targeting. Since a
putative targeting mechanism of CS implies phosphorylation-dependent steps in the
endoplasmic reticulum (ER) and/or Golgi complex, five CS-HA1 mutants disrupting
the three phosphorylation sites of CS (Thr(189), Thr(229), and Thr(353)) were
engineered by either site-directed mutagenesis or deletion: CS-HA1DeltaP1
(Thr(189) --> Ile); CS-HA1DeltaP2 (Thr(229) --> Asn); CS-HA1DeltaP1,2; in which
Thr(189) and Thr(229) were changed to Ile and Asn, respectively; and CS
HA1Delta14(COOH) and CS-HA1Delta49 (COOH), in which 14 residues (Glu(354)
Asp(367)) and 49 residues (Asp(319)-Asp(367)), respectively, were deleted at the
carboxy-terminal. Mutant cDNAs were transiently transfected in either HeLa cells,
cultured myoblasts of rat skeletal muscle, or regenerating soleus muscle fibers
of adult rats. Each CS-HA1 mutant was identified by Western blot as a single
polypeptide of the predicted molecular weight. The intracellular localization of
CS-HA1 mutants was studied by immunofluorescence using specific antibodies
against either CS or HA1. CS-HA1 mutants colocalized with ER markers, e.g.,
calreticulin, and partially overlapped with Golgi complex markers, e.g., alpha
mannosidase II, in HeLa cells and myotubes. CS-HA1 mutants were expressed and
retained in ER and ER/SR of HeLa cells and myotubes, respectively, and correctly
segregated to jSR of regenerating soleus muscle fibers. Thus, the targeting
mechanism of CS in vivo is not affected by phosphorylation(s); i.e., sorting and
segregation of CS appear to be independent of posttranslational
phosphorylation(s).
PMID- 11010810
TI - Effector mechanisms of fenretinide-induced apoptosis in neuroblastoma.
AB - Fenretinide is an effective inducer of apoptosis in many malignancies but its
precise mechanism(s) of action in the induction of apoptosis in neuroblastoma is
unclear. To characterize fenretinide-induced apoptosis, neuroblastoma cell lines
were treated with fenretinide and flow cytometry was used to measure apoptosis,
free radical generation, and mitochondrial permeability changes. Fenretinide
induced high levels of caspase-dependent apoptosis accompanied by an increase in
free radicals and the release of cytochrome c in the absence of mitochondrial
permeability transition. Apoptosis was blocked by two retinoic acid receptor
(RAR)-beta/gamma-specific antagonists, but not by an RARalpha-specific
antagonist. Free radical induction in response to fenretinide was not blocked by
the caspase inhibitor ZVAD or by RAR antagonists and was only marginally reduced
in cells selected for resistance to fenretinide. Therefore, free radical
generation may be only one of a number of intracellular mechanisms of apoptotic
signaling in response to fenretinide. These results suggest that the effector
pathway of fenretinide-induced apoptosis of neuroblastoma is caspase dependent,
involving mitochondrial release of cytochrome c independently of permeability
changes, and mediated by specific RARs. As the mechanism of action of fenretinide
may be different from other retinoids, this compound may be a valuable adjunct to
neuroblastoma therapy with retinoic acid and conventional chemotherapeutic drugs.
PMID- 11010811
TI - Inhibition of cell growth and apoptosis by inducible expression of the
transcriptional repressor Mad1.
AB - Mad1 is a Myc antagonist that heterodimerizes with Max and functions as a
transcriptional repressor. We have studied the effects of Mad1 on cell growth,
cell cycle distribution, and apoptosis using Mad1-inducible cell lines.
Expression of Mad1 inhibited cell proliferation, S-phase entry, and colony
formation, changes that were accompanied by a reduction in CDK2 activity. The
inhibition of Mad1 on cell proliferation was potentiated by serum starvation and
was paralleled by accumulation of cells in the G0/G1 and the G2 phases of the
cell cycle. Mad1 also reduced apoptosis induced by serum withdrawal and by the
cytostatic drug cisplatinum. The effects on both cell growth and apoptosis were
dependent on the mSin3 interaction domain of Mad1, which is necessary for
recruitment of histone deacetylases and corepressors, suggesting that
transcriptional repression is mediating these functions. Taken together with the
expression pattern of Mad1, these results suggest that Mad1 plays an important
role during initiation of differentiation by inhibiting cell proliferation and
blocking apoptosis.
PMID- 11010812
TI - Differential induction of gelatinase B (MMP-9) and gelatinase A (MMP-2) in T
lymphocytes upon alpha(4)beta(1)-mediated adhesion to VCAM-1 and the CS-1 peptide
of fibronectin.
AB - Integrin alpha(4)beta(1) on the surface of T lymphocytes interacts with vascular
cell adhesion molecule-1 (VCAM-1) and fibronectin during migration of lymphocytes
from the blood to sites of inflammation. Migrating lymphocytes actively modify
their environment through a number of mechanisms including proteolysis of the
extracellular matrix by matrix metalloproteinases (MMP) synthesized by the cells.
In this study, expression of MMP upon alpha(4)beta(1)-mediated adhesion of
leukocytes to two major ligands, the IIICS-1 domain of fibronectin and VCAM-1,
has been examined. Adhesion of T lymphoblastoid Jurkat cells to the CS-1 peptide
induced expression of mRNA for two MMPs, gelatinase A (MMP-2) and gelatinase B
(MMP-9). As evaluated by relative RT-PCR and Northern blot analyses, the level of
mRNA was upregulated about 4- to 5-fold for both MMPs compared to control cells
maintained in suspension. With time, both enzymes were detected in conditioned
media and inside the cells, and their identities were verified by Western
blotting and gelatin zymography. Adhesion of Jurkat cells to the second major
alpha(4)beta(1) ligand, VCAM-1, upregulated mRNA for MMP-2 (3.5-fold) and failed
to induce expression of mRNA for MMP-9. Accordingly, only MMP-2 protein was
detected in conditioned media of cells adherent to VCAM-1. Occupancy of
alpha(4)beta(1) on the surface of suspended cells with soluble CS-1 peptide or
VCAM-1 did not upregulate synthesis and release of MMPs. A similar pattern of
induction of MMPs after adhesion to CS-1 and VCAM-1 was observed in T lymphocytes
isolated from human blood. These results demonstrate that adhesion of T
lymphocytes through alpha(4)beta(1) to different ligands, which bind to similar
or overlapping sites in the integrin, induces intracellular events leading to
distinct patterns of MMPs biosynthesis.
PMID- 11010813
TI - The whole meiotic process can occur in vitro in untransformed rat spermatogenic
cells.
AB - The aim of the present study was to assess whether the whole meiotic process of
spermatogenic cells is able to take place in vitro. Fragments of seminiferous
tubules from 20- to 22- or 28-day-old rats were seeded in medium containing 0.2%
fetal calf serum in bicameral chambers and then cultured for 4 weeks in a
chemically defined medium. The differentiation of meiotic germinal cells was
followed by four criteria: (i) ultramicroscopic examination of the different
types of germ cells present in the cell layer throughout the culture period; (ii)
determination of the changes in DNA content per nucleus of the cell population
seeded with time in culture; (iii) assessment of the ability of germinal cells to
transcribe genes expressed after completion of meiosis; and (iv) monitoring the
fate of BrdU-labeled leptotene spermatocytes. The ultrastructural study showed
that the overall organization of the cells in the culture well recalls that of
the seminiferous epithelium throughout the culture period. Moreover the
identification of young round spermatids 21 days after seeding suggested that
these spermatids had been formed very recently in culture. Determination of DNA
content per nucleus showed that a 1C cell population could be observed after
several days of cultures reaching 6 to 10% of total cells. An exponential-like
increase in the amounts of the mRNAs encoding for TP1 or TP2 occurred from the
time when 1C cells appeared in the culture until the end of the experiment.
Finally, BrdU-labeled leptotene spermatocytes differentiated into pachytene
spermatocytes and then into secondary spermatocytes, and BdrU-labeled round
spermatids were observed from Day 21 of culture onward. Taken together these
results indicate that the whole meiotic process from leptotene spermatocyte to
round spermatid can indeed occur in vitro under the present culture conditions.
PMID- 11010814
TI - 14-3-3 protein family members have a regulatory role in retinoic acid-mediated
induction of cytokeratins in F9 cells.
AB - We have found that the expression of five 14-3-3 protein isoforms is induced
during the retinoic acid (RA)-mediated differentiation of mouse embryonal
carcinoma F9 cells. The induced expression of the 14-3-3 proteins is presumed to
have a role in enhancing the mitogen-activated protein kinase (MAPK) activity
during RA-mediated F9 cell differentiation, because using genetically engineered
budding yeast we showed that these isoforms enhanced the signaling in the MAPK
cascade mainly through the interaction with Raf-1. Then we assessed the role of
increased MAPK activity in F9 cell differentiation by interfering with signaling
in the MAPK cascade in F9 cells. The exogenous expression of dominant-negative
MEK1 efficiently abrogated RA-mediated induction of the cytokeratins EndoA and
EndoC in the F9 cells. These results suggest that the 14-3-3 proteins play a role
in the efficient induction of the cytokeratins during F9 cell differentiation
through their signal enhancing activity in the MAPK cascade.
PMID- 11010815
TI - A conformational change in PBX1A is necessary for its nuclear localization.
AB - The fly homeodomain (HD) protein EXTRADENTICLE (EXD) is dependent on a second HD
protein, HOMOTHORAX (HTH), for nuclear localization. We show here that in insect
cells the mammalian homolog of EXD, PBX1A, shows a similar dependence on the HTH
homologs MEIS1, 2, and 3 and the MEIS-like protein PREP1. Paradoxically, removal
of residues N-terminal to the PBX1A HD abolishes interactions with MEIS/PREP but
allows nuclear accumulation of PBX1A. We use deletion mapping and fusion to green
fluorescent protein to map two cooperative nuclear localization signals (NLSs) in
the PBX HD. The results of DNA-binding assays and pull-down experiments are
consistent with a model whereby the PBX N-terminus binds to the HD and masks the
two NLSs. In support of the model, a mutation in the PBX HD that disrupts contact
with the N-terminus leads to constitutive nuclear localization. The HD mutation
also increases sensitivity to protease digestion, consistent with a change in
conformation. We propose that MEIS family proteins induce a conformational change
in PBX that unmasks the NLS, leading to nuclear localization and increased DNA
binding activity. Consistent with this, PBX1 is nuclear only where Meis1 is
expressed in the mouse limb bud.
PMID- 11010816
TI - Centrosome-specific perturbations during in vitro maturation of mouse oocytes
exposed to cocaine.
AB - Previous studies indicating that cocaine may perturb meiotic chromosome
segregation in mammalian oocytes prompted an analysis of the effects of cocaine
on mouse oocytes matured in vitro under defined exposure conditions. Cumulus
enclosed mouse oocytes were matured in vitro in the continuous presence of
cocaine and assessed for meiotic cell cycle progression and centrosome
microtubule organization using a combination of cytogenetic and fluorescence
microscopic techniques. Both of these approaches demonstrated that cocaine had
little effect on meiotic cell cycle progression to metaphase of meiosis-2 except
at the highest dose tested (1000 microg/ml) where progression from metaphase-1 to
metaphase-2 was inhibited. Cytogenetic analyses further showed that bivalent
segregation was moderately affected and the incidence of premature centromere
separation was significantly decreased following cocaine treatment. Under
conditions of cocaine exposure, striking changes in meiotic spindle structure and
cytoplasmic centrosome organization were observed. A 36% reduction in spindle
length was associated with a loss of nonacetylated microtubules and fragmentation
of spindle pole centrosomes. Moreover, in oocytes exposed to cocaine during
maturation, a doubling in cytoplasmic centrosome number was observed. These
results are discussed with respect to the relative roles of chromosomes and
centrosomes in establishing and maintaining functional microtubule organization
during meiosis in oocytes.
PMID- 11010817
TI - Growth state-dependent binding of USF-1 to a proximal promoter E box element in
the rat plasminogen activator inhibitor type 1 gene.
AB - Induced PAI-1 gene expression in renal epithelial (NRK-52E, clone EC-1) cells
occurs as part of the immediate-early response to serum. PAI-1 transcripts are
maximally expressed early in G(1) (within 4 h of serum addition to quiescent EC-1
cells) and then subsequently decline to basal levels prior to entry into DNA
synthetic phase. Comparative analysis of PAI-1 mRNA abundance and de novo
synthesized thiolated RNA in quiescent cells, as well as at 4 h (early G(1)) and
20 h (late G(2)) postserum addition, in conjunction with RNA decay measurements
indicated that PAI-1 gene regulation upon growth activation was predominantly
transcriptional. An E box motif (CACGTG), important in the induced expression of
some growth state-dependent genes, mapped to nucleotides -160 to -165 upstream of
the transcription start site in the PAI-1 proximal promoter. Mobility-shift
assessments, using a 18-bp deoxyoligonucleotide construct containing the E box
within the context of PAI-1-specific flanking sequences, confirmed binding of EC
1 nuclear protein(s) to this probe and, specifically, to the E box hexanucleotide
site. The specificity of this protein-probe interaction was verified by
competition analyses with double-stranded DNA constructs that included E box
deoxyoligonucleotides with non-PAI-1 flanking bases, mutant E box sequences
incapable of binding NRK nuclear proteins, and unrelated (i.e., AP-1) target
motifs. Extract immunodepletion and supershift/complex-blocking experiments
identified one PAI-1 E box-binding protein to be upstream stimulatory factor-1
(USF-1), a member of the HLH family of transcription factors. Mutation of the
CACGTG site to TCCGTG in an 18-bp PAI-1 probe inhibited the formation of USF-1
containing complexes confirming that an intact E box motif at -160 to -165 bp in
the PAI-1 promoter and, in particular, the CA residues at -165 and -164 are
essential for USF-1 binding. Incorporation of this 2 bp change into a reporter
construct containing 764 bp of the proximal PAI-1 "promoter" ligated to a CAT
gene effectively reduced (by 74%) CAT activity in cycling cells. An intact E box
motif at nucleotides -160 to -165 in the PAI-1 promoter, thus, is an important
functional element in the regulation of PAI-1 transcriptional activity in renal
cells.
PMID- 11010818
TI - Epidermal growth factor receptor efficiently activates mitogen-activated protein
kinase in HeLa cells and Hep2 cells conditionally defective in clathrin-dependent
endocytosis.
AB - Epidermal growth factor (EGF)-induced signaling was investigated in cells
conditionally defective in clathrin-dependent endocytosis by overexpression of
K44A dynamin in HeLa cells and potassium depletion in Hep2 cells. Overexpression
of mutant dynamin disrupts high-affinity EGF-EGF receptor (EGFR) interaction (T.
Ringerike, E. Stang, L. E. Johannessen, D. Sandnes, F. O. Levy, and I. H.
Madshus, 1998, J. Biol. Chem. 273, 16639-16642). However, the EGFR substrates Shc
and c-Cbl were as efficiently tyrosine phosphorylated in endocytosis-deficient
HeLa cells exhibiting only low-affinity EGFRs as in HeLa cells with intact
endocytosis and with both high- and low-affinity EGFRs. Both Raf and mitogen
activated protein kinase (MAPK) were activated to the same extent and with the
same kinetics. HeLa cells distributed equally in the cell cycle regardless of
EGFR internalization. Upon potassium depletion of Hep2 cells, EGF-induced EGFR
endocytosis was inhibited. However, the EGFR and MAPK were efficiently activated
by EGF in both the absence and the presence of clathrin-dependent endocytosis.
The EGFR was weakly tyrosine phosphorylated by potassium depletion even in the
absence of EGF, and this activation resulted in detectable activation of MAPK.
Our results demonstrate that internalization of EGFR by clathrin-dependent
endocytosis is not required for activation of MAPK.
PMID- 11010819
TI - Stem cell characteristics of transplanted rat mammary clonogens.
AB - Rat mammary glands contain a subpopulation of clonogenic epithelial cells with
large proliferation and differentiation potentials. When transplanted, the
clonogens in monodispersed rat mammary epithelial cell suspensions give rise to
either alveolar units (AUs) or ductal units (DUs) depending on the nature of the
hormonal milieu in the graft recipient. Clonogens are also the primary cells of
origin of mammary cancer following exposure to ionizing radiation or chemical
carcinogens. Given the other stem cell characteristics of mammary clonogens, it
would be expected that the primary AUs and DUs to which they give rise when
grafted and hormonally stimulated (a) would be derived from the same clonogenic
cell subpopulation, (b) would contain all of the functionally differentiated cell
types of homologous parts of comparably stimulated mammary glands in situ, and
(c) would also contain clonogen subpopulations capable when subtransplanted of
giving rise to secondary AUs and DUs of similar cell composition. The current
experiments were designed to test these expectations. The data are discussed in
the context of results of previous studies with this and other experimental
models. The results further support the conclusion that rat mammary clonogens are
multipotent mammary stem cells.
PMID- 11010820
TI - Effects of antiandrogens on chromatin remodeling and transcription of the
integrated mouse mammary tumor virus promoter.
AB - Inhibition of the ligand-activated androgen receptor (AR) by antiandrogens plays
an important role in the treatment of various hyperandrogenic disorders including
prostate cancer. However, the molecular mechanisms of antiandrogen activity in
vivo remain unclear. In this study we analyzed the effects of cyproterone acetate
(CPA), flutamide (F), and hydroxyflutamide (OHF) on transcriptional activation
and chromatin remodeling of the genomically integrated mouse mammary tumor virus
(MMTV) promoter. This promoter has provided an excellent model system to study
the impact of steroid hormones on transcriptional activation in the context of a
defined chromatin structure. The MMTV hormone response element is positioned on a
phased nucleosome, which becomes remodeled in response to steroids. We utilized
this model system in mouse L-cell fibroblasts that contain a stably integrated
MMTV promoter. In these cells, dihydrotestosterone (DHT) induced a large increase
of AR protein levels that correlated with transcriptional activation and
chromatin remodeling of the MMTV promoter. Coadministration of DHT and CPA or DHT
and OHF in these cells inhibited the increase of AR levels, which resulted in a
strong blockage of transcriptional activation and chromatin remodeling of the
MMTV promoter. In contrast, F had no significant influence on these activities.
We conclude that a major portion of the antiandrogenic effects of CPA and OHF in
vivo are mediated by the reduction of AR levels.
PMID- 11010821
TI - Homocysteine inhibits retinoic acid synthesis: a mechanism for homocysteine
induced congenital defects.
AB - Hyperhomocysteinemia is frequently associated with congenital defects of the
heart and neural tube and is a suspected pathogenic factor in atherosclerosis and
neoplasia. Results in the present report show homocysteine treatment disrupts
normal development of avian embryos; and this effect is prevented by retinoic
acid. Based on this, we hypothesize that homocysteine may exert its teratogenic
effects by disrupting retinoic acid signaling during development. A reporter cell
line transfected with a retinoic acid response element (RARE) linked to a lacZ
reporter gene was used to identify the site of retinoid inhibition. Using this
reporter cell line, we show that homocysteine inhibits the oxidation of retinal
to retinoic acid with concentrations of homocysteine that are in the
pathophysiological range (.05 to 0.5 mM). In contrast, homocysteine
concentrations as high as 5 mM are unable to inhibit the induction of lacZ by
retinoic acid. We show that cellular uptake of homocysteine is sensitive to the
specific L-system transport inhibitor, bicycloheptane, and bicycloheptane blocks
the inhibition of retinoic acid synthesis by homocysteine, demonstrating that
this inhibition occurs intracellularly. These results suggest that homocysteine
induced congenital defects are due to the specific ability of homocysteine to
inhibit conversion of retinal to retinoic acid.
PMID- 11010822
TI - Inactivation of Ca(2+) action potential channels by the MEK inhibitor PD98059.
AB - In a previous study involving the inhibition of mitogen-activated protein kinase
(MAPK) activation during fertilization of the marine worm Urechis caupo, we found
that PD98059, but not U0126, caused multiple sperm penetrations in oocytes (Gould
and Stephano, 1999, Dev. Biol. 216, 348-358). Since these oocytes are protected
against polyspermy by a positive shift in membrane potential at fertilization
(Gould-Somero et al., 1979, J. Cell Biol. 82, 426-440), we investigated the
effects of PD98059 on the electrical properties of the oocyte membrane. PD98059,
but not U0126, selectively blocked the voltage-dependent Ca(2+) channels that
participate in the electrical polyspermy block. We also noted previously that
PD98059 had more serious effects than U0126 on chromosome behavior during
meiosis. This, too, could be explained by the effect on Ca(2+) channels, since
when U0126-treated eggs were fertilized in low Ca(2+) seawater to reduce Ca(2+)
uptake, similar effects were produced. These results show that PD98059 has side
effects unrelated to the inhibition of MAPK activation and underscores the need
for caution in interpreting the results of experiments with this widely used MEK
inhibitor.
PMID- 11010823
TI - Immunology of bacille Calmette-Guerin and related topics.
PMID- 11010824
TI - Preventing tuberculosis with bacillus Calmette-Guerin vaccine: a meta-analysis of
the literature.
AB - This article reviews a previously published meta-analysis of 1264 titles or
abstracts and 70 selected studies for evaluation of the efficacy of bacillus
Calmette-Guerin (BCG) vaccine in preventing tuberculosis. Following review, data
from 26 studies were included in the analysis. These 26 studies reveal that
vaccination with BCG significantly reduces the risk of tuberculosis by an average
of 50%. This level of protection persists across a number of subgroups defined by
age at vaccination and study design. Vaccination with BCG was significantly
associated with a reduction in the incidence of pulmonary tuberculosis and
extrapulmonary disease. In general, the results of this meta-analysis lend weight
and confidence to arguments favoring the use of BCG vaccine.
PMID- 11010825
TI - Animal models for experimental tuberculosis.
AB - Animal models for tuberculosis vaccine assays have evolved through a series of
sequential experiments aimed at optimizing the activity of a particular vaccine
product. As a result, studies that use different animal models do not agree on
the potency ranking of antituberculosis vaccines, and each major test-system
variable contributes to the disagreement. Disagreements among laboratories about
the efficacy of vaccines are in part due to differences in test systems. A survey
of potency assays of tuberculosis vaccines suggests that, based on the choice of
a specific combination of variables in the test model, an investigator can show
that any given vaccine product has superior potency. In view of these problems
with animal models for research on tuberculosis vaccines, we recommend that
attention should be focused on those animal models that replicate the key aspects
of the natural history of human tuberculosis. The development of vaccines by
means of new technologies requires animal models to assay the protective potency
of vaccines that, ideally, inhibit tubercle bacilli at the point of infection.
The development of new tuberculosis vaccines may be handled most efficiently in a
joint venture that includes both laboratories involved in vaccine production and
laboratories concerned with animal models.
PMID- 11010826
TI - What does tuberculin reactivity after bacille Calmette-Guerin vaccination tell
us?
AB - The effect of bacille Calmette-Guerin (BCG) vaccination on tuberculin reactivity
is briefly reviewed. BCG vaccination will almost invariably result in tuberculin
conversion with a positive tuberculin skin test developing 4-8 weeks after
vaccination. However, these tuberculin reactions will wane-rapidly in all
individuals who receive the vaccine in the neonatal period and more slowly in
those who are vaccinated at an older age such as during the primary-school years.
Of BCG vaccine recipients whose initial tuberculin skin test is negative, 10%-25%
will have a positive tuberculin skin test if they are retested within 1-4 weeks
the so-called "booster phenomenon. " There is no relationship between tuberculin
reactivity after BCG vaccination and the protective efficacy of the vaccine
against development of active tuberculosis. Therefore, the ideal BCG vaccine
would produce a scar at the site of injection to identify individuals who have
been vaccinated but would have no effect on tuberculin reactivity.
PMID- 11010827
TI - Management of adverse reactions to bacille Calmette-Guerin vaccine.
AB - Published reports appear to underestimate the true rate of adverse reactions to
bacille Calmette-Guerin (BCG) vaccine. At a recent national conference on
tuberculosis control among aboriginal populations, lack of awareness of what
constitutes an adverse reaction was considered a possible contributing factor to
underreporting. The following review defines a normal BCG response and discusses
the management of complications when they occur.
PMID- 11010828
TI - An analysis of some hypotheses related to the Chingelput bacille Calmette-Guerin
trial.
AB - Investigation of several hypotheses related to the outcome of the Chingelput
Bacille Calmette-Guerin (BCG) Trial suggests at least 2 factors that might
explain the major scientific puzzle of a protective effect expected of 80% and a
protective effect observed of 0% (i.e., equivalent protection for BCG and
placebo). One factor that explains some of the low efficacy observed for BCG in
this trial is the virtual saturation level of exposure to environmental
mycobacteria (EM). Studies in animal models demonstrated that the protection
afforded by infection with EM was equivalent to the protection that resulted from
BCG vaccination. The second factor, pathogenetic pathway, explains why there was
still a high case rate for tuberculosis, even though the population was fully
vaccinated by EM. This hypothesis states that tuberculosis in India, as well as
in most developing countries, results primarily from exogenous reinfection, a
pathway against which BCG (or EM) exerts no protective effect beyond that induced
by the first episode of infection with Mycobacterium tuberculosis.
PMID- 11010829
TI - The Bcg host-resistance gene.
AB - In the mouse, resistance and susceptibility to intracellular growth of
mycobacteria in macrophages is controlled by the Bcg (Nramp1) gene, which has
been cloned and shown to encode a macrophage phagosomal membrane protein with a
putative transporter function. In the homologous human NRAMP1 gene, a total of 11
polymorphisms have been identified, which are being used to test for the linkage
of NRAMP1 alleles with human responses to mycobacteria, including susceptibility
to tuberculosis and leprosy, as well as BCG immunotherapy in bladder cancer.
PMID- 11010830
TI - Efficacy and safety of bacille Calmette-Guerin immunotherapy in superficial
bladder cancer.
AB - In the United States, bladder cancer is the fourth most common human malignancy.
In the past decade, the incidence of bladder cancer has increased by 36%.
However, mortality has declined by 8%. Intravesical chemotherapy was considered
to be partially responsible for this improvement in survival, but a recent review
of clinical studies shows no reduction in disease progression with intravesical
chemotherapy. Fortunately, the results of immunotherapy with bacille Calmette
Guerin (BCG) are quite different, and it is expected that patients treated with
optimal BCG treatment regimens will have a long-term reduction in tumor
recurrence, tumor progression, and cancer mortality.
PMID- 11010831
TI - Mechanisms of action of intravesical bacille Calmette-Guerin: local immune
mechanisms.
AB - The local immune response to mycobacteria is complex, but mycobacterial antigen
presentation by phagocytes to T helper cells is the pivotal interaction. Bacille
Calmette-Guerin (BCG) vaccination is associated with the development of
antituberculosis immunity but not necessarily with antitumor immunity. Animal
studies have shown that an intact host immune system is required for the
antitumor activity of BCG. Immunosuppressed and, particularly, T cell-depleted
individuals fail to respond to BCG immunotherapy. Clinical and laboratory
evidence suggest that the antitumor activity is concentrated at the site of BCG
administration, which reinforces the view that local immune mechanisms are
responsible for this phenomenon.
PMID- 11010832
TI - In vitro generation of bacillus Calmette-Guerin-activated killer cells.
AB - Tumor regression induced in cancer patients by local instillation of bacillus
Calmette-Guerin (BCG) into the bladder is considered to be mediated by cellular
immune and inflammatory reactions. In an attempt to elucidate which of these
effects are relevant to tumoricidal activity, an in vitro system was employed in
which the immunostimulatory effects of BCG could be studied. This report
describes the induction of BCG-activated killer (BAK) cells, which effectively
lyse bladder tumor cells. Human peripheral blood mononuclear cells (PBMC) were
stimulated with viable and sonicated BCG (v-BCG and s-BCG, respectively) to
generate BAK cells. Cytotoxicity of BAK cells was comparable with the
cytotoxicity exerted by lymphokine-activated killer (LAK) cells generated by
interferon (IFN)-gamma but did not reach the level of interleukin-2 (IL-2)
generated LAK cells. Induction of BAK cells was possible only with v-BCG and not
with s-BCG. By depletion and enrichment of defined cell populations, the
cytotoxic potential of BAK cells could be attributed to a population of CD8(+)
and CD56(+) double-positive lymphocytes. Macrophages and CD4(+) cells were
required for the induction of killing activity but had no such activity by
themselves. Furthermore, the presence of IFN-gamma and IL-2 in the supernatants
harvested during the generation of BAK cells was demonstrated. Monoclonal
antibodies neutralizing these cytokines abolished BCG-mediated cytotoxicity. From
these results, it is concluded that the known beneficial effect of local
instillation of BCG on maintenance of the relapse-free state in superficial
bladder cancer may be due to local generation of BAK cells.
PMID- 11010833
TI - Reduction of side effects of intravesical therapy with bacille Calmette-Guerin by
pentoxifylline?--an in vitro approach.
AB - Immunotherapy with intravesical bacille Calmette-Guerin (BCG) is the treatment of
choice against superficial bladder cancer recurrences. However, this therapy is
associated with side effects that are considered to be the result of inflammatory
cytokines. Since pentoxifylline is known to interfere with the production of
cytokines, this drug was tested in vitro with regard to a later clinical
application in BCG-treated patients. The cytokine release and the cytotoxicity of
interleukin-2 or BCG-stimulated mononuclear cells were analyzed, and the growth
of BCG under the influence of pentoxifylline was assayed. The results showed an
inhibition of cytokine release of stimulated mononuclear cells. The cytotoxicity
of BCG-stimulated mononuclear cells but not of lymphokine-stimulated mononuclear
cells against bladder carcinoma cells was significantly inhibited. Restimulation
with fresh BCG restored cytotoxicity. Direct coincubation of BCG and
pentoxifylline resulted in a reduction of mycobacterial metabolism. From these
data, we conclude that the use of pentoxifylline to reduce BCG-related side
effects should be tested further in a clinical study.
PMID- 11010834
TI - Role of animal models in understanding intravesical therapy with bacille Calmette
Guerin.
AB - Animal models provide a vehicle for understanding basic biological questions.
Through the use of animal models, adequate control of experimental design is
possible so that rigorous experiments can be performed to test a hypothesis. In
the case of testing therapeutic mechanisms, it is important to select a model
that is most analogous to the clinical setting so that observations can be
readily transferred to clinical studies for validation. In mechanistic studies of
Mycobacterium bovis strain (bacille Calmette-Guerin) therapy for bladder cancer,
the orthotopic animal model most closely mimics the clinical treatment of bladder
cancer.
PMID- 11010835
TI - Immunostimulation in the urinary bladder by local application of Nocardia rubra
cell-wall skeletons (Rubratin) and bacillus Calmette-Guerin as therapy for
superficial bladder cancer: a comparative study.
AB - Twelve patients with superficial bladder cancer were treated with intravesical
instillations of Rubratin (ASTA Pharma AG, Frankfurt, Germany), a cell-wall
preparation of Nocardia rubra. The objective was to compare the immunostimulating
effect of Rubratin with that of bacillus Calmette-Guerin (BCG). Local
immunostimulation was determined by cytokine induction in serially collected
urine samples during the first 24 h after each instillation, leukocyte influx
into the urine, and phenotypic analysis of the lymphocyte fraction. Levels of
Rubratin-induced interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha
were significantly elevated compared with pretherapy levels. Rubratin induced
leukocyte influx into the urine. T-cell activation (IL-2 receptor and human
leukocyte antigen-DR expression) can be induced, and CD4:CD8 cell ratios can be
increased. All parameters indicated that Rubratin-induced immunostimulation was
less than that associated with BCG. In conclusion, although local Rubratin
induced immunostimulation occurs in a limited number of patients, the amount of
immunocompetent cells attracted to the bladder seems to be less than that
associated with BCG therapy, thus resulting in lower levels of cytokine
production (which may reflect less clinical efficacy).
PMID- 11010836
TI - Bacille Calmette-Guerin vaccine.
PMID- 11010837
TI - HLA class I alleles associated with susceptibility or resistance to human
immunodeficiency virus type 1 infection among a population in Chaco Province,
Argentina.
AB - Host genetic factors, such as HLA alleles, are important in human
immunodeficiency virus (HIV) infection and its progression to AIDS. HLA class I
gene products are involved in peptide presentation, and each allele is
responsible for presenting a different set of peptides to cytotoxic T
lymphocytes. The increase or decrease in the frequency of certain alleles in HIV
1-positive versus control subjects would suggest that alleles play a role in
susceptibility to or protection against this viral infection. In the present
study, 56 HIV-1-positive patients in Chaco Province, Argentina, were typed for
the HLA-A and HLA-B loci, using polymerase chain reaction and sequence-specific
oligonucleotide probes. The frequency of alleles A*24, B*18, and B*39 was
increased in HIV-1-positive subjects, suggesting that these alleles play a role
in susceptibility to HIV-1 infection. Alleles B*44 and B*55 were not found in HIV
1-positive subjects, suggesting that they have a protective effect against the
disease. The P values of the alleles B*39 and B*44 were statistically significant
(P<.05).
PMID- 11010838
TI - Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial
virus vaccine candidate in infancy.
AB - A live-attenuated, intranasal respiratory syncytial virus (RSV) candidate
vaccine, cpts-248/404, was tested in phase 1 trials in 114 children, including 37
1-2-month-old infants-a target age for RSV vaccines. The cpts-248/404 vaccine was
infectious at 104 and 105 plaque-forming units in RSV-naive children and was
broadly immunogenic in children >6 months old. Serum and nasal antibody responses
in 1-2 month olds were restricted to IgA, had a dominant response to RSV G
protein, and had no increase in neutralizing activity. Nevertheless, there was
restricted virus shedding on challenge with a second vaccine dose and preliminary
evidence for protection from symptomatic disease on natural reexposure. The cpts
248/404 vaccine candidate did not cause fever or lower respiratory tract illness.
In the youngest infants, however, cpts-248/404 was unacceptable because of upper
respiratory tract congestion associated with peak virus recovery. A live
attenuated RSV vaccine for the youngest infant will use cpts-248/404 modified by
additional attenuating mutations.
PMID- 11010839
TI - Treatment-mediated changes in human immunodeficiency virus (HIV) type 1 RNA and
CD4 cell counts as predictors of weight growth failure, cognitive decline, and
survival in HIV-infected children.
AB - This meta-analysis of 5 large studies of the Pediatric AIDS Clinical Trials Group
was undertaken to evaluate the predictive value of antiretroviral treatment
mediated changes in 3 markers of human immunodeficiency virus (HIV) type 1
disease progression-HIV-1 RNA level, CD4 cell count, and CD4 percentage-for
weight growth failure, cognitive decline, and survival in HIV-infected children.
Proportional hazards models were used to assess the prognostic value of the
markers at baseline and after 24 weeks of treatment, with data from 1089
children. Among children receiving nucleoside with or without nonnucleoside
reverse-transcriptase inhibitors, higher immunologic and lower virologic markers
at baseline and after 24 weeks were significant independent predictors of
survival, whereas virologic markers were significant predictors of weight growth
and cognitive failure in children >1 year old. The finding of differential age
effects on pediatric-specific clinical outcomes emphasizes the need for continued
investigation of treatment effects in children.
PMID- 11010840
TI - The relationship between virus load response to highly active antiretroviral
therapy and change in CD4 cell counts: A report from the Women's interagency HIV
study.
AB - The relationship between the pattern of virus load response to highly active
antiretroviral therapy (HAART) and CD4 lymphocyte response was assessed in a
cohort of 249 human immunodeficiency virus (HIV) type 1-infected women at 3
times: 1 before and 2 after initiation of therapy, with follow-up of 6-12 months.
Patients with a durable response to HAART (i.e., >1 log decrease in HIV-1 RNA
sustained for the study periods) had a continuous and significant increase in CD4
cell counts over time, whereas those with no response (<0.5 log decrease in HIV-1
RNA) had a slight decline. Patients with a mixed response (initial decrease >1
log, followed by a subsequent decrease <0.5 log) had an increase in CD4 cell
count, followed by a plateau. The trend in CD4 cell count differed significantly
by response to HAART, with those patients who experienced a durable response
having significantly higher CD4 cell counts than others.
PMID- 11010841
TI - Infectious disease morbidity in the US region bordering Mexico, 1990-1998.
AB - The United States and Mexico share an international boundary approximately 3000
km long. This border separates 2 nations with great differences in health status.
The objective of this study was to assess morbidity due to infectious diseases in
the US region bordering Mexico. The incidence between 1990 and 1998 of 22
nationally notifiable infectious diseases was compared between border and
nonborder regions. Disease rates, reflected as rate ratios, were higher in the
border region for botulism, brucellosis, diphtheria, hepatitis A, measles, mumps,
rabies, rubella, salmonellosis, and shigellosis than in either of 2 nonborder
comparison regions. These data indicate that incidence rates for a variety of
infectious diseases of public health importance are significantly higher in the
United States along the Mexican border than in nonborder regions. These results
suggest that an inadequate public health infrastructure may contribute to excess
morbidity due to infectious diseases in the border region.
PMID- 11010842
TI - Phylogenetic subgroups of human T cell lymphotropic virus (HTLV) type I in the
tax gene and their association with different risks for HTLV-I-associated
myelopathy/tropical spastic paraparesis.
AB - The association between human T cell lymphotropic virus (HTLV) type I tax
variation and disease outcome was studied. The tax gene was sequenced in 61
patients with HTLV-I-associated myelopathy/tropical spastic paraparesis
(HAM/TSP), 55 patients with adult T cell leukemia, and 62 healthy carriers (HCs).
Phylogenetic analysis revealed 2 tax gene subgroups that are related on the basis
of the long terminal repeat sequence. Further analysis using restriction fragment
length polymorphism in 192 patients with HAM/TSP and 200 HCs revealed a higher
incidence of 1 tax subgroup (taxA) in HAM/TSP. taxA was present in 30 (15.5%) of
192 patients with HAM/TSP and in 14 (7%) of 200 HCs. The difference was
significant (chi2=6.47; P=.014; odds ratio, 2.46; 95% confidence interval, 1.26
4.80). This effect was independent of HLA-A*02, which has been reported to
prevent HAM/TSP development. These findings suggest that both host genetic
factors and HTLV-I subgroup are associated with different risks for development
of HAM/TSP.
PMID- 11010856
TI - Inactivation of Escherichia coli and Listeria innocua in milk by combined
treatment with high hydrostatic pressure and the lactoperoxidase system.
AB - We have studied inactivation of four strains each of Escherichia coli and
Listeria innocua in milk by the combined use of high hydrostatic pressure and the
lactoperoxidase-thiocyanate-hydrogen peroxide system as a potential mild food
preservation method. The lactoperoxidase system alone exerted a bacteriostatic
effect on both species for at least 24 h at room temperature, but none of the
strains was inactivated. Upon high-pressure treatment in the presence of the
lactoperoxidase system, different results were obtained for E. coli and L.
innocua. For none of the E. coli strains did the lactoperoxidase system increase
the inactivation compared to a treatment with high pressure alone. However, a
strong synergistic interaction of both treatments was observed for L. innocua.
Inactivation exceeding 7 decades was achieved for all strains with a mild
treatment (400 MPa, 15 min, 20 degrees C), which in the absence of the
lactoperoxidase system caused only 2 to 5 decades of inactivation depending on
the strain. Milk as a substrate was found to have a considerable effect
protecting E. coli and L. innocua against pressure inactivation and reducing the
effectiveness of the lactoperoxidase system under pressure on L. innocua. Time
course experiments showed that L. innocua counts continued to decrease in the
first hours after pressure treatment in the presence of the lactoperoxidase
system. E. coli counts remained constant for at least 24 h, except after
treatment at the highest pressure level (600 MPa, 15 min, 20 degrees C), in which
case, in the presence of the lactoperoxidase system, a transient decrease was
observed, indicating sublethal injury rather than true inactivation.
PMID- 11010857
TI - Differential C isotope discrimination by fungi during decomposition of C(3)- and
C(4)-derived sucrose.
AB - Stable isotope analysis is a major tool used in ecosystem studies to establish
pathways and rates of C exchange between various ecosystem components. Little is
known about isotopic effects of many such components, especially microbes. Here
we report on the discovery of an unexpected pattern of C isotopic discrimination
by basidiomycete fungi with far-reaching consequences for our understanding of
isotopic processing in ecosystems where these microbes mediate material transfers
across trophic levels. We measured fractionation effects on three ecologically
relevant basidiomycete species under controlled laboratory conditions. Sucrose
derived from C(3) and C(4) plants is fractionated differentially by these
microbes in a taxon-specific manner. The differentiation between mycorrhizal and
saprotrophic fungi observed in the field by others is not explained by intrinsic
discrimination patterns. Fractionation occurs during sugar uptake and is
sensitive to the nonrandom distribution of stable isotopes in the sucrose
molecule. The balance between respiratory physiology and fermentative physiology
modulates the degree of fractionation. These discoveries disprove the assumption
that fungal C processing does not significantly alter the distribution of stable
C isotopes and provide the basis for a reevaluation of ecosystem models based on
isotopic evidence that involve C transfer across microbial interfaces. We provide
a mechanism to account for the observed differential discrimination effects.
PMID- 11010858
TI - Urea hydrogen peroxide reduces the numbers of lactobacilli, nourishes yeast, and
leaves no residues in the ethanol fermentation.
AB - Urea hydrogen peroxide (UHP) at a concentration of 30 to 32 mmol/liter reduced
the numbers of five Lactobacillus spp. (Lactobacillus plantarum, L. paracasei,
Lactobacillus sp. strain 3, L. rhamnosus, and L. fermentum) from approximately
10(7) to approximately 10(2) CFU/ml in a 2-h preincubation at 30 degrees C of
normal-gravity wheat mash at approximately 21 g of dissolved solids per ml
containing normal levels of suspended grain particles. Fermentation was completed
36 h after inoculation of Saccharomyces cerevisiae in the presence of UHP, even
when wheat mash was deliberately contaminated (infected) with L. paracasei at
approximately 10(7) CFU/ml. There were no significant differences in the maximum
ethanol produced between treatments when urea hydrogen peroxide was used to kill
the bacteria and controls (in which no bacteria were added). However, the
presence of L. paracasei at approximately 10(7) CFU/ml without added agent
resulted in a 5.84% reduction in the maximum ethanol produced compared to the
control. The bactericidal activity of UHP is greatly affected by the presence of
particulate matter. In fact, only 2 mmol of urea hydrogen peroxide per liter was
required for disinfection when mashes had little or no particulate matter
present. No significant differences were observed in the decomposition of
hydrogen peroxide in normal-gravity wheat mash at 30 degrees C whether the
bactericidal agent was added as H(2)O(2) or as urea hydrogen peroxide. NADH
peroxidase activity (involved in degrading H(2)O(2)) increased significantly (P =
0.05) in the presence of 0.75 mM hydrogen peroxide (sublethal level) in all five
strains of lactobacilli tested but did not persist in cells regrown in the
absence of H(2)O(2). H(2)O(2)-resistant mutants were not expected or found when
lethal levels of H(2)O(2) or UHP were used. Contaminating lactobacilli can be
effectively managed by UHP, a compound which when used at ca. 30 mmol/liter
happens to provide near-optimum levels of assimilable nitrogen and oxygen that
aid in vigorous fermentation performance by yeast.
PMID- 11010859
TI - Seasonal population dynamics and interactions of competing bacteriophages and
their host in the rhizosphere.
AB - We describe two prolonged bacteriophage blooms within sugar beet rhizospheres
ensuing from an artificial increase in numbers of an indigenous soil bacterium.
Further, we provide evidence of in situ competition between these phages. This is
the first in situ demonstration of such microbial interactions in soil. To
achieve this, sugar beet seeds were inoculated with Serratia liquefaciens CP6RS
or its lysogen, CP6RS-ly-phi 1. These were sown, along with uninoculated seeds,
in 36 field plots arranged in a randomized Latin square. The plots were then
sampled regularly over 194 days, and the plants were assayed for the released
bacteria and any infectious phages. Both the lysogen and nonlysogen forms of
CP6RS survived equally well in situ, contradicting earlier work suggesting
lysogens have a competitive disadvantage in nature. A Podoviridae phage,
identified as phi CP6-4, flourished on the nonlysogen-inoculated plants in
contrast to those plants inoculated with the lysogen. Conversely, the
Siphoviridae phage phi CP6-1 (used to construct the released lysogen) was
isolated abundantly from the lysogen-treated plants but almost never on the
nonlysogen-inoculated plants. The uninoculated plants also harbored some phi CP6
1 phage up to day 137, yet hardly any phi CP6-4 phages were found, and this was
consistent with previous years. We show that the different temporal and spatial
distributions of these two physiologically distinct phages can be explained by
application of optimal foraging theory to phage ecology. This is the first time
that such in situ evidence has been provided in support of this theoretical
model.
PMID- 11010860
TI - A strain of Enterococcus faecium (18C23) inhibits adhesion of enterotoxigenic
Escherichia coli K88 to porcine small intestine mucus.
AB - Few studies, if any, have addressed the adhesion of enterococci to the intestinal
mucosa and their interference with the adhesion of pathogens, although more than
60% of probiotic preparations in the market contain strains of enterococci. The
objective of this study was to investigate if Enterococcus faecium 18C23 has the
ability to inhibit the adhesion of Escherichia coli K88ac and K88MB to the small
intestine mucus of piglets. Approximately 9% of E. faecium 18C23 organisms
adhered to the small intestine mucus, and the adhesion was found to be specific.
Living E. faecium 18C23 culture efficiently inhibited the adhesion of E. coli
K88ac and K88MB to the piglet intestine mucus. Inhibition of the adhesion of E.
coli K88ac to the small intestine mucus was found to be dose dependent.
Inhibition of >90% was observed when 10(9) CFU or more of living E. faecium 18C23
culture per ml was added simultaneously with E. coli to immobilized mucus. The
substances from both the 18C23 cells and the spent culture supernatant
contributed to the inhibition of adhesion of E. coli K88 to the small intestine
mucus receptors. The inhibiting effect was not solely a pH effect since
considerable inhibitory action was demonstrated after neutralizing the mixture or
spent culture supernatant to pH 7.0. Part of the inhibition of adhesion of E.
coli K88ac by E. faecium 18C23 or its supernatant might occur through steric
hindrance.
PMID- 11010861
TI - Rapid mineralization of benzo[a]pyrene by a microbial consortium growing on
diesel fuel.
AB - A microbial consortium which rapidly mineralized the environmentally persistent
pollutant benzo[a]pyrene was recovered from soil. The consortium cometabolically
converted [7-(14)C]benzo[a]pyrene to (14)CO(2) when it was grown on diesel fuel,
and the extent of benzo[a]pyrene mineralization was dependent on both diesel fuel
and benzo[a]pyrene concentrations. Addition of diesel fuel at concentrations
ranging from 0.007 to 0.2% (wt/vol) stimulated the mineralization of 10 mg of
benzo[a]pyrene per liter 33 to 65% during a 2-week incubation period. When the
benzo[a]pyrene concentration was 10 to 100 mg liter(-1) and the diesel fuel
concentration was 0.1% (wt/vol), an inoculum containing 1 mg of cell protein per
liter (small inoculum) resulted in mineralization of up to 17.2 mg of
benzo[a]pyrene per liter in 16 days. This corresponded to 35% of the added
radiolabel when the concentration of benzo[a]pyrene was 50 mg liter(-1). A
radiocarbon mass balance analysis recovered 25% of the added benzo[a]pyrene
solubilized in the culture suspension prior to mineralization. Populations
growing on diesel fuel most likely promoted emulsification of benzo[a]pyrene
through the production of surface-active compounds. The consortium was also
analyzed by PCR-denaturing gradient gel electrophoresis of 16S rRNA gene
fragments, and 12 dominant bands, representing different sequence types, were
detected during a 19-day incubation period. The onset of benzo[a]pyrene
mineralization was compared to changes in the consortium community structure and
was found to correlate with the emergence of at least four sequence types. DNA
from 10 sequence types were successfully purified and sequenced, and that data
revealed that eight of the consortium members were related to the class
Proteobacteria but that the consortium also included members which were related
to the genera Mycobacterium and Sphingobacterium.
PMID- 11010862
TI - Chemostat enrichments of human feces with resistant starch are selective for
adherent butyrate-producing clostridia at high dilution rates.
AB - Resistant starch (RS) enrichments were made using chemostats inoculated with
human feces from two individuals at two dilution rates (D = 0.03 h(-1) and D =
0.30 h(-1)) to select for slow- and fast-growing amylolytic communities. The
fermentations were studied by analysis of short-chain fatty acids, amylase and
alpha-glucosidase activities, and viable counts of the predominant culturable
populations and the use of 16S rRNA-targeted oligonucleotide probes. Considerable
butyrate was produced at D = 0. 30 h(-1), which corresponded with reduced
branched-chain fatty acid formation. At both dilution rates, high levels of
extracellular amylase activity were produced, while alpha-glucosidase was
predominantly cell associated. Bacteroides and bifidobacteria predominated at the
low dilution rate, whereas saccharolytic clostridia became more important at D =
0.30 h(-1). Microscopic examination showed that within 48 h of inoculation, one
particular bacterial morphotype predominated in RS enrichments at D = 0.30 h(-1).
This organism attached apically to RS granules and formed rosette-like structures
which, with glycocalyx formation, agglomerated to form biofilm networks in the
planktonic phase. Attempts to isolate this bacterium in pure culture were
repeatedly unsuccessful, although a single colony was eventually obtained. On the
basis of its 16S rDNA sequence, this RS-degrading, butyrate-producing organism
was identified as being a previously unidentified group I Clostridium sp. A 16S
rRNA-targeted probe was designed using this sequence and used to assess the
abundance of the population in the enrichments. At 240 h, its contributions to
total rRNA in the chemostats were 5 and 23% at D = 0.03 and 0.30 h(-1),
respectively. This study indicates that bacterial populations with significant
metabolic potential can be overlooked using culture-based methodologies. This may
provide a paradigm for explaining the discrepancy between the low numbers of
butyrate-producing bacteria that are isolated from fecal samples and the actual
production of butyrate.
PMID- 11010863
TI - Evolution of thermotolerance in hot spring cyanobacteria of the genus
Synechococcus.
AB - The extension of ecological tolerance limits may be an important mechanism by
which microorganisms adapt to novel environments, but it may come at the
evolutionary cost of reduced performance under ancestral conditions. We combined
a comparative physiological approach with phylogenetic analyses to study the
evolution of thermotolerance in hot spring cyanobacteria of the genus
Synechococcus. Among the 20 laboratory clones of Synechococcus isolated from
collections made along an Oregon hot spring thermal gradient, four different 16S
rRNA gene sequences were identified. Phylogenies constructed by using the
sequence data indicated that the clones were polyphyletic but that three of the
four sequence groups formed a clade. Differences in thermotolerance were observed
for clones with different 16S rRNA gene sequences, and comparison of these
physiological differences within a phylogenetic framework provided evidence that
more thermotolerant lineages of Synechococcus evolved from less thermotolerant
ancestors. The extension of the thermal limit in these bacteria was correlated
with a reduction in the breadth of the temperature range for growth, which
provides evidence that enhanced thermotolerance has come at the evolutionary cost
of increased thermal specialization. This study illustrates the utility of using
phylogenetic comparative methods to investigate how evolutionary processes have
shaped historical patterns of ecological diversification in microorganisms.
PMID- 11010864
TI - Biochemical and genetic characterization of propionicin T1, a new bacteriocin
from Propionibacterium thoenii.
AB - A collection of propionibacteria was screened for bacteriocin production. A new
bacteriocin named propionicin T1 was isolated from two strains of
Propionibacterium thoenii. This bacteriocin shows no sequence similarity to other
bacteriocins. Propionicin T1 was active against all strains of Propionibacterium
acidipropionici, Propionibacterium thoenii, and Propionibacterium jensenii tested
and also against Lactobacillus sake NCDO 2714 but showed no activity against
Propionibacterium freudenreichii. The bacteriocin was purified, and the N
terminal part of the peptide was determined with amino acid sequencing. The
corresponding gene pctA was sequenced, and this revealed that propionicin T1 is
produced as a prebacteriocin of 96 amino acids with a typical sec leader, which
is processed to give a mature bacteriocin of 65 amino acids. An open reading
frame encoding a protein of 424 amino acids was found 68 nucleotides downstream
the stop codon of pctA. The N-terminal part of this putative protein shows strong
similarity with the ATP-binding cassette of prokaryotic and eukaryotic ABC
transporters, and this protein may be involved in self-protection against
propionicin T1. Propionicin T1 is the first bacteriocin from propionibacteria
that has been isolated and further characterized at the molecular level.
PMID- 11010865
TI - Bacterial community structure associated with a dimethylsulfoniopropionate
producing North Atlantic algal bloom.
AB - The bacteria associated with oceanic algal blooms are acknowledged to play
important roles in carbon, nitrogen, and sulfur cycling, yet little information
is available on their identities or phylogenetic affiliations. Three culture
independent methods were used to characterize bacteria from a
dimethylsulfoniopropionate (DMSP)-producing algal bloom in the North Atlantic.
Group-specific 16S rRNA-targeted oligonucleotides, 16S ribosomal DNA (rDNA) clone
libraries, and terminal restriction fragment length polymorphism analysis all
indicated that the marine Roseobacter lineage was numerically important in the
heterotrophic bacterial community, averaging >20% of the 16S rDNA sampled. Two
other groups of heterotrophic bacteria, the SAR86 and SAR11 clades, were also
shown by the three 16S rRNA-based methods to be abundant in the bloom community.
In surface waters, the Roseobacter, SAR86, and SAR11 lineages together accounted
for over 50% of the bacterial rDNA and showed little spatial variability in
abundance despite variations in the dominant algal species. Depth profiles
indicated that Roseobacter phylotype abundance decreased with depth and was
positively correlated with chlorophyll a, DMSP, and total organic sulfur
(dimethyl sulfide plus DMSP plus dimethyl sulfoxide) concentrations. Based on
these data and previous physiological studies of cultured Roseobacter strains, we
hypothesize that this lineage plays a role in cycling organic sulfur compounds
produced within the bloom. Three other abundant bacterial phylotypes
(representing a cyanobacterium and two members of the alpha Proteobacteria) were
primarily associated with chlorophyll-rich surface waters of the bloom (0 to 50
m), while two others (representing Cytophagales and delta Proteobacteria) were
primarily found in deeper waters (200 to 500 m).
PMID- 11010866
TI - Substrate specificity of atrazine chlorohydrolase and atrazine-catabolizing
bacteria.
AB - Bacterial atrazine catabolism is initiated by the enzyme atrazine chlorohydrolase
(AtzA) in Pseudomonas sp. strain ADP. Other triazine herbicides are metabolized
by bacteria, but the enzymological basis of this is unclear. Here we begin to
address this by investigating the catalytic activity of AtzA by using substrate
analogs. Purified AtzA from Pseudomonas sp. strain ADP catalyzed the hydrolysis
of an atrazine analog that was substituted at the chlorine substituent by
fluorine. AtzA did not catalyze the hydrolysis of atrazine analogs containing the
pseudohalide azido, methoxy, and cyano groups or thiomethyl and amino groups.
Atrazine analogs with a chlorine substituent at carbon 2 and N-alkyl groups,
ranging in size from methyl to t-butyl, all underwent dechlorination by AtzA.
AtzA catalyzed hydrolytic dechlorination when one nitrogen substituent was
alkylated and the other was a free amino group. However, when both amino groups
were unalkylated, no reaction occurred. Cell extracts were prepared from five
strains capable of atrazine dechlorination and known to contain atzA or closely
homologous gene sequences: Pseudomonas sp. strain ADP, Rhizobium strain PATR,
Alcaligenes strain SG1, Agrobacterium radiobacter J14a, and Ralstonia picketti D.
All showed identical substrate specificity to purified AtzA from Pseudomonas sp.
strain ADP. Cell extracts from Clavibacter michiganensis ATZ1, which also
contains a gene homologous to atzA, were able to transform atrazine analogs
containing pseudohalide and thiomethyl groups, in addition to the substrates used
by AtzA from Pseudomonas sp. strain ADP. This suggests that either (i) another
enzyme(s) is present which confers the broader substrate range or (ii) the AtzA
itself has a broader substrate range.
PMID- 11010867
TI - A methylotrophic pathway participates in pectin utilization by Candida boidinii.
AB - The methylotrophic yeast Candida boidinii S2 was found to be able to grow on
pectin or polygalacturonate as a carbon source. When cells were grown on 1%
(wt/vol) pectin, C. boidinii exhibited induced levels of the pectin
depolymerizing enzymes pectin methylesterase (208 mU/mg of protein), pectin lyase
(673 mU/mg), pectate lyase (673 mU/mg), and polygalacturonase (3.45 U/mg) and two
methanol-metabolizing peroxisomal enzymes, alcohol oxidase (0.26 U/mg) and
dihydroxyacetone synthase (94 mU/mg). The numbers of peroxisomes also increased
ca. two- to threefold in cells grown on these pectic compounds (3.34 and 2.76
peroxisomes/cell for cells grown on pectin and polygalacturonate, respectively)
compared to the numbers in cells grown on glucose (1.29 peroxisomes/cell). The
cell density obtained with pectin increased as the degree of methyl
esterification of pectic compounds increased, and it decreased in strains from
which genes encoding alcohol oxidase and dihydroxyacetone synthase were deleted
and in a peroxisome assembly mutant. Our study showed that methanol metabolism
and peroxisome assembly play important roles in the degradation of pectin,
especially in the utilization of its methyl ester moieties.
PMID- 11010868
TI - A bead-based method for multiplexed identification and quantitation of DNA
sequences using flow cytometry.
AB - A new multiplexed, bead-based method which utilizes nucleic acid hybridizations
on the surface of microscopic polystyrene spheres to identify specific sequences
in heterogeneous mixtures of DNA sequences is described. The method consists of
three elements: beads (5.6-microm diameter) with oligomer capture probes attached
to the surface, three fluorophores for multiplexed detection, and flow cytometry
instrumentation. Two fluorophores are impregnated within each bead in varying
amounts to create different bead types, each associated with a unique probe. The
third fluorophore is a reporter. Following capture of fluorescent cDNA sequences
from environmental samples, the beads are analyzed by flow cytometric techniques
which yield a signal intensity for each capture probe proportional to the amount
of target sequences in the analyte. In this study, a direct hybrid capture assay
was developed and evaluated with regard to sequence discrimination and
quantitation of abundances. The target sequences (628 to 728 bp in length) were
obtained from the 16S/23S intergenic spacer region of microorganisms collected
from polluted groundwater at the nuclear waste site in Hanford, Wash. A
fluorescence standard consisting of beads with a known number of fluorescent DNA
molecules on the surface was developed, and the resolution, sensitivity, and
lower detection limit for measuring abundances were determined. The results were
compared with those of a DNA microarray using the same sequences. The bead method
exhibited far superior sequence discrimination and possesses features which
facilitate accurate quantitation.
PMID- 11010869
TI - Application of 5'-nuclease PCR for quantitative detection of Listeria
monocytogenes in pure cultures, water, skim milk, and unpasteurized whole milk.
AB - PCR techniques have significantly improved the detection and identification of
bacterial pathogens. Countless adaptations and applications have been described,
including quantitative PCR and the latest innovation, real-time PCR. In real-time
PCR, e.g., the 5'-nuclease chemistry renders the automated and direct detection
and quantification of PCR products possible (P. M. Holland et al., Proc. Natl.
Acad. Sci. USA 88:7276-7280, 1991). We present an assay for the quantitative
detection of Listeria monocytogenes based on the 5'-nuclease PCR using a 113-bp
amplicon from the listeriolysin O gene (hlyA) as the target. The assay was
positive for all isolates of L. monocytogenes tested (65 isolates including the
type strain) and negative for all other Listeria strains (16 isolates from five
species tested) and several other bacteria (18 species tested). The application
of 5'-nuclease PCR in diagnostics requires a quantitative sample preparation
step. Several magnetic bead-based strategies were evaluated, since these systems
are simple and relatively easy to automate. The combination of nonspecific
binding of bacteria to paramagnetic beads, with subsequent DNA purification by
use of the same beads, gave the most satisfactory result. The detection limit was
approximately 6 to 60 CFU, quantification was linear over at least 7 log units,
and the method could be completed within 3 h. In conclusion, a complete
quantitative method for L. monocytogenes in water and in skimmed and raw milk was
developed.
PMID- 11010870
TI - Development of genetic tools for Lactobacillus sakei: disruption of the beta
galactosidase gene and use of lacZ as a reporter gene To study regulation of the
putative copper ATPase, AtkB.
AB - Downstream from the ptsHI operon of Lactobacillus sakei, the genes atkY and atkB,
organized in an operon, were observed. The two putative proteins, AtkB and AtkY,
show sequence similarity to the Enterococcus hirae copper P-type ATPase,
responsible for copper efflux, and its negative regulator. Characterization of
AtkB as a copper P-type ATPase could not be demonstrated since an atkB mutant did
not show any phenotype. Thus, another strategy was followed in order to
investigate the transcriptional regulation of the atkYB locus, leading to the
development of new genetic tools for L. sakei. A plasmid was constructed, the use
of which allowed gene replacement at the lacLM locus in L. sakei by two
successive crossovers. A strain deleted of the lacLM operon encoding the beta
galactosidase of L. sakei was constructed by this method, and the Escherichia
coli lacZ gene could then be used as a reporter gene to investigate the
regulation of atkYB. Results show that the atkYB operon is induced by small
concentrations of CuSO(4) (30 to 40 microM) but not when CuSO(4) is omitted or
added at higher concentrations.
PMID- 11010871
TI - Characterization, seasonal occurrence, and diel fluctuation of
poly(hydroxyalkanoate) in photosynthetic microbial mats.
AB - In situ poly(hydroxyalkanoate) (PHA) levels and repeating-unit compositions were
examined in stratified photosynthetic microbial mats from Great Sippewissett Salt
Marsh, Mass., and Ebro Delta, Spain. Unlike what has been observed in pure
cultures of phototrophic bacteria, the prevalence of hydroxyvalerate (HV)
repeating units relative to hydroxybutyrate (HB) repeating units was striking. In
the cyanobacteria-dominated green material of Sippewissett mats, the mole percent
ratio of repeating units was generally 1HB:1HV. In the purple sulfur bacteria
dominated pink material the relationship was typically 1HB:2HV. In Sippewissett
mats, PHA contributed about 0.5 to 1% of the organic carbon in the green layer
and up to 6% in the pink layer. In Ebro Delta mats, PHA of approximately 1HB:2HV
repeating-unit distribution contributed about 2% of the organic carbon of the
composite photosynthetic layers (the green and pink layers were not separated).
Great Sippewissett Salt Marsh mats were utilized for more extensive investigation
of seasonal, diel, and exogenous carbon effects. When the total PHA content was
normalized to organic carbon, there was little seasonal variation in PHA levels.
However, routine daily variation was evident at all sites and seasons. In every
case, PHA levels increased during the night and decreased during the day. This
phenomenon was conspicuous in the pink layer, where PHA levels doubled overnight.
The daytime declines could be inhibited by artificial shading. Addition of
exogenous acetate, lactate, and propionate induced two- to fivefold increases in
the total PHA levels when applied in the daylight but had no effect when applied
at night. The distinct diel pattern of in situ PHA accumulation at night appears
to be related, in some phototrophs, to routine dark energy metabolism and is not
influenced by the availability of organic nutrients.
PMID- 11010872
TI - Generation of new hydrogen-recycling Rhizobiaceae strains by introduction of a
novel hup minitransposon.
AB - Hydrogen evolution by nitrogenase is a source of inefficiency for the nitrogen
fixation process by the Rhizobium-legume symbiosis. To develop a strategy to
generate rhizobial strains with H(2)-recycling ability, we have constructed a Tn5
derivative minitransposon (TnHB100) that contains the ca. 18-kb H(2) uptake (hup)
gene cluster from Rhizobium leguminosarum bv. viciae UPM791. Bacteroids from
TnHB100-containing strains of R. leguminosarum bv. viciae PRE, Bradyrhizobium
japonicum, R. etli, and Mesorhizobium loti expressed high levels of hydrogenase
activity that resulted in full recycling of the hydrogen evolved by nitrogenase
in nodules. Efficient processing of the hydrogenase large subunit (HupL) in these
strains was shown by immunoblot analysis of bacteroid extracts. In contrast,
Sinorhizobium meliloti, M. ciceri, and R. leguminosarum bv. viciae UML2 strains
showed poor expression of the hup system that resulted in H(2)-evolving nodules.
For the latter group of strains, no immunoreactive material was detected in
bacteroid extracts using anti-HupL antiserum, suggesting a low level of
transcription of hup genes or HupL instability. A general procedure for the
characterization of the minitransposon insertion site and removal of antibiotic
resistance gene included in TnHB100 has been developed and used to generate
engineered strains suitable for field release.
PMID- 11010873
TI - Cloning, expression, and characterization of the katG gene, encoding catalase
peroxidase, from the polycyclic aromatic hydrocarbon-degrading bacterium
Mycobacterium sp. strain PYR-1.
AB - A 81-kDa protein from Mycobacterium sp. strain PYR-1 was expressed in response to
exposure of the strain to the polycyclic aromatic hydrocarbon pyrene and
recovered by two-dimensional gel electrophoresis. The N-terminal sequence of the
protein indicated that it was similar to catalase-peroxidase. An oligonucleotide
probe designed from this sequence was used to screen a genomic library of
Mycobacterium sp. strain PYR-1, and a positive clone, containing a part of the
gene encoding the 81-kDa protein, was isolated. A gene-walking technique was used
to sequence the entire gene, which was identified as katG for catalase
peroxidase. The deduced KatG protein sequence showed significant homology to
KatGII of Mycobacterium fortuitum and clustered with catalase-peroxidase proteins
from other Mycobacterium species in a phylogenetic tree. The katG gene was
expressed in Escherichia coli to produce a protein with catalase-peroxidase
activity. Since the induction of this catalase-peroxidase occurred in pyrene
induced cultures and the exposure of these cultures to hydrogen peroxide reduced
pyrene metabolism, our data suggest that this enzyme plays a role in polycyclic
aromatic hydrocarbon metabolism by strain PYR-1.
PMID- 11010874
TI - Cytological effects of cellulases in the parasitism of Phytophthora parasitica by
Pythium oligandrum.
AB - The ubiquitous oomycete Pythium oligandrum is a potential biocontrol agent for
use against a wide range of pathogenic fungi and an inducer of plant disease
resistance. The ability of P. oligandrum to compete with root pathogens for
saprophytic colonization of substrates may be critical for pathogen increase in
soil, but other mechanisms, including antibiosis and enzyme production, also may
play a role in the antagonistic process. We used transmission electron microscopy
and gold cytochemistry to analyze the intercellular interaction between P.
oligandrum and Phytophthora parasitica. Growth of P. oligandrum towards
Phytophthora cells correlated with changes in the host, including retraction of
the plasma membrane and cytoplasmic disorganization. These changes were
associated with the deposition onto the inner host cell surface of a cellulose
enriched material. P. oligandrum hyphae could penetrate the thickened host cell
wall and the cellulose-enriched material, suggesting that large amounts of
cellulolytic enzymes were produced. Labeling of cellulose with gold-complexed
exoglucanase showed that the integrity of the cellulose was greatly affected both
along the channel of fungal penetration and also at a distance from it. We
measured cellulolytic activity of P. oligandrum in substrate-free liquid medium.
The enzymes present were almost as effective as those from Trichoderma viride in
degrading both carboxymethyl cellulose and Phytophthora wall-bound cellulose. P.
oligandrum and its cellulolytic enzymes may be useful for biological control of
oomycete pathogens, including Phytophthora and Pythium spp., which are frequently
encountered in field and greenhouse production.
PMID- 11010875
TI - Quantitative flow cytometric evaluation of maximal Cryptosporidium parvum oocyst
infectivity in a neonate mouse model.
AB - The importance of waterborne transmission of Cryptosporidium parvum to humans has
been highlighted by recent outbreaks of cryptosporidiosis. The first step in a
survey of contaminated water currently consists of counting C. parvum oocysts.
Data suggest that an accurate risk evaluation should include a determination of
viability and infectivity of counted oocysts in water. In this study, oocyst
infectivity was addressed by using a suckling mouse model. Four-day-old NMRI
(Naval Medical Research Institute) mice were inoculated per os with 1 to 1,000
oocysts in saline. Seven days later, the number of oocysts present in the entire
small intestine was counted by flow cytometry using a fluorescent, oocyst
specific monoclonal antibody. The number of intestinal oocysts was directly
related to the number of inoculated oocysts. For each dose group, infectivity of
oocysts, expressed as the percentage of infected animals, was 100% for challenge
doses between 25 and 1,000 oocysts and about 70% for doses ranging from 1 to 10
oocysts/animal. Immunofluorescent flow cytometry was useful in enhancing the
detection sensitivity in the highly susceptible NMRI suckling mouse model and so
was determined to be suitable for the evaluation of maximal infectivity risk.
PMID- 11010876
TI - Use of two-dimensional electrophoresis To study differential protein expression
in divercin V41-resistant and wild-type strains of Listeria monocytogenes.
AB - The use of bacteriocins from food-grade lactic acid bacteria to fight against the
food-borne pathogen Listeria monocytogenes has been gaining interest. However,
the emergence of resistant cells is frequently reported when Listeria is exposed
to such antibacterials. A two-dimensional electrophoresis study of whole-cell
protein expression of Listeria monocytogenes variants sensitive or resistant to
the action of a bacteriocin produced by Carnobacterium divergens V41, divercin
V41, is reported in this paper. The resistant variant obtained from the sensitive
strain of L. monocytogenes P was also resistant to piscicocins V1 and SF668, but
remained sensitive to nisin. Its growth rate was 50% less than the sensitive
strain, and the MIC for it was 10(4) times higher. No reversion of the resistance
was observed after 20 successive cultures in the absence of divercin V41.
Comparison of the protein patterns by two-dimensional gel electrophoresis
analysis showed clear differences. In the resistant variant pattern, at least
nine spots had disappeared and eight new ones were observed. One of the newly
synthesized proteins was identified as a flagellin of L. monocytogenes. Direct
interaction between flagellin and divercin V41 was not evidenced. Intracellular
synthesis of flagellin is probably an indirect effect of a modification in
transcriptional regulation with widespread effects through a sigma factor. An
intense protein, only present in the sensitive strain, was identified as a non
heme iron-binding ferritin displaying strong similarities to Dps proteins. Common
modifications in the transcriptional regulation for these two proteins are
discussed.
PMID- 11010877
TI - Characterization of reutericyclin produced by Lactobacillus reuteri LTH2584.
AB - Lactobacillus reuteri LTH2584 exhibits antimicrobial activity that can be
attributed neither to bacteriocins nor to the production of reuterin or organic
acids. We have purified the active compound, named reutericyclin, to homogeneity
and characterized its antimicrobial activity. Reutericyclin exhibited a broad
inhibitory spectrum including Lactobacillus spp., Bacillus subtilis, B. cereus,
Enterococcus faecalis, Staphylococcus aureus, and Listeria innocua. It did not
affect the growth of gram-negative bacteria; however, the growth of
lipopolysaccharide mutant strains of Escherichia coli was inhibited.
Reutericyclin exhibited a bactericidal mode of action against Lactobacillus
sanfranciscensis, Staphylococcus aureus, and B. subtilis and triggered the lysis
of cells of L. sanfranciscensis in a dose-dependent manner. Germination of spores
of B. subtilis was inhibited, but the spores remained unaffected under conditions
that do not permit germination. The fatty acid supply of the growth media had a
strong effect on reutericyclin production and its distribution between producer
cells and the culture supernatant. Reutericyclin was purified from cell extracts
and culture supernatant of L. reuteri LTH2584 cultures grown in mMRS by solvent
extraction, gel filtration, RP-C(8) chromatography, and anion-exchange
chromatography, followed by rechromatography by reversed-phase high-pressure
liquid chromatography. Reutericyclin was characterized as a negatively charged,
highly hydrophobic molecule with a molecular mass of 349 Da. Structural
characterization (A. Holtzel, M. G. Ganzle, G. J. Nicholson, W. P. Hammes, and G.
Jung, Angew. Chem. Int. Ed. 39:2766-2768, 2000) revealed that reutericyclin is a
novel tetramic acid derivative. The inhibitory activity of culture supernatant of
L. reuteri LTH2584 corresponded to that of purified as well as synthetic
reutericyclin.
PMID- 11010878
TI - Involvement of an extracellular protease in algicidal activity of the marine
bacterium Pseudoalteromonas sp. strain A28.
AB - The marine bacterium Pseudoalteromonas sp. strain A28 was able to kill the diatom
Skeletonema costatum strain NIES-324. The culture supernatant of strain A28
showed potent algicidal activity when it was applied to a paper disk placed on a
lawn of S. costatum NIES-324. The condensed supernatant, which was prepared by
subjecting the A28 culture supernatant to ultrafiltration with a 10,000-M(w)
cutoff membrane, showed algicidal activity, suggesting that strain A28 produced
extracellular substances capable of killing S. costatum cells. The condensed
supernatant was then found to have protease and DNase activities. Two
Pseudoalteromonas mutants lacking algicidal activity, designated NH1 and NH2,
were selected after N-methyl-N'-nitrosoguanidine mutagenesis. The culture
supernatants of NH1 and NH2 showed less than 15% of the protease activity
detected with the parental strain, A28. The protease was purified to homogeneity
from A28 culture supernatants by using ion-exchange chromatography followed by
preparative gel electrophoresis. Paper-disk assays revealed that the purified
protease had potent algicidal activity. The purified protease had a molecular
mass for 50 kDa, and the N-terminal amino acid sequence was determined to be Ala
Thr-Pro-Asn-Asp-Pro. The optimum pH and temperature of the protease were found to
be 8.8 and 30 degrees C, respectively, by using succinyl-Ala-Ala-Pro-Phe-p
nitroanilide as a substrate. The protease activity was strongly inhibited by
phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate, antipain,
chymostatin, and leupeptin. No significant inhibition was detected with EDTA,
EGTA, phenanthroline or tetraethylenepentamine. These results suggest that
Pseudoalteromonas sp. strain A28 produced an extracellular serine protease which
was responsible for the algicidal activity of this marine bacterium.
PMID- 11010879
TI - Molecular characterization of Yarrowia lipolytica and Candida zeylanoides
isolated from poultry.
AB - Yeast isolates from raw and processed poultry products were characterized using
PCR amplification of the internally transcribed spacer (ITS) 5.8S ribosomal DNA
region (ITS-PCR), restriction analysis of amplified products, randomly amplified
polymorphic DNA (RAPD) analysis, and pulsed-field gel electrophoresis (PFGE). ITS
PCR resulted in single fragments of 350 and 650 bp, respectively, from eight
strains of Yarrowia lipolytica and seven strains of Candida zeylanoides.
Digestion of amplicons with HinfI and HaeIII produced two fragments of 200 and
150 bp from Y. lipolytica and three fragments of 350, 150, and 100 bp from C.
zeylanoides, respectively. Although these fragments showed species-specific
patterns and confirmed species identification, characterization did not enable
intraspecies typing. Contour-clamped heterogeneous electric field PFGE separated
chromosomal DNA of Y. lipolytica into three to five bands, most larger than 2
Mbp, whereas six to eight bands in the range of 750 to 2,200 bp were obtained
from C. zeylanoides. Karyotypes of both yeasts showed different polymorphic
patterns among strains. RAPD analysis, using enterobacterial repetitive
intergenic sequences as primers, discriminated between strains within the same
species. Cluster analysis of patterns formed groups that correlated with the
source of isolation. For ITS-PCR, extraction of DNA by boiling yeast cells was
successfully used.
PMID- 11010880
TI - Cold shock induction of thermal sensitivity in Listeria monocytogenes.
AB - Cold shock at 0 to 15 degrees C for 1 to 3 h increased the thermal sensitivity of
Listeria monocytogenes. In a model broth system, thermal death time at 60 degrees
C was reduced by up to 45% after L. monocytogenes Scott A was cold shocked for 3
h. The duration of the cold shock affected thermal tolerance more than did the
magnitude of the temperature downshift. The Z values were 8.8 degrees C for
controls and 7.7 degrees C for cold-shocked cells. The D values of cold-shocked
cells did not return to control levels after incubation for 3 h at 28 degrees C
followed by heating at 60 degrees C. Nine L. monocytogenes strains that were cold
shocked for 3 h exhibited D(60) values that were reduced by 13 to 37%. The D
value reduction was greatest in cold-shocked stationary-phase cells compared to
cells from cultures in either the lag or exponential phases of growth. In
addition, cold-shocked cells were more likely to be inactivated by a given heat
treatment than nonshocked cells, which were more likely to experience sublethal
injury. The D values of chloramphenicol-treated control cells and chloramphenicol
treated cold-shocked cells were no different from those of untreated cold-shocked
cells, suggesting that cold shock suppresses synthesis of proteins responsible
for heat protection. In related experiments, the D values of L. monocytogenes
Scott A were decreased 25% on frankfurter skins and 15% in ultra-high temperature
milk if the inoculated products were first cold shocked. Induction of increased
thermal sensitivity in L. monocytogenes by thermal flux shows potential to become
a practical and efficacious preventative control method.
PMID- 11010881
TI - Cold shock and its effect on ribosomes and thermal tolerance in Listeria
monocytogenes.
AB - Differential scanning calorimetry (DSC) and fatty acid analysis were used to
determine how cold shocking reduces the thermal stability of Listeria
monocytogenes. Additionally, antibiotics that can elicit production of cold or
heat shock proteins were used to determine the effect of translation blockage on
ribosome thermal stability. Fatty acid profiles showed no significant variations
as a result of cold shock, indicating that changes in membrane fatty acids were
not responsible for the cold shock-induced reduction in thermal tolerance.
Following a 3-h cold shock from 37 to 0 degrees C, the maximum denaturation
temperature of the 50S ribosomal subunit and 70S ribosomal particle peak was
reduced from 73.4 +/- 0.1 degrees C (mean +/- standard deviation) to 72.1 +/- 0.5
degrees C (P < or = 0.05), indicating that cold shock induced instability in the
associated ribosome structure. The maximum denaturation temperature of the 30S
ribosomal subunit peak did not show a significant shift in temperature (from 67.5
+/- 0.4 degrees C to 66.8 +/- 0.5 degrees C) as a result of cold shock,
suggesting that either 50S subunit or 70S particle sensitivity was responsible
for the intact ribosome fragility. Antibiotics that elicited changes in maximum
denaturation temperature in ribosomal components also elicited reductions in
thermotolerance. Together, these data suggest that ribosomal changes resulting
from cold shock may be responsible for the decrease in D value observed when L.
monocytogenes is cold shocked.
PMID- 11010882
TI - PCR primers that amplify fungal rRNA genes from environmental samples.
AB - Two PCR primer pairs were designed to amplify rRNA genes (rDNA) from all four
major phyla of fungi: Ascomycota, Basidiomycota, Chytridomycota, and Zygomycota.
PCRs performed with these primers showed that both pairs amplify DNA from
organisms representing the major taxonomic groups of fungi but not from nonfungal
sources. To test the ability of the primers to amplify fungal rDNA from
environment samples, clone libraries from two avocado grove soils were
constructed and analyzed. These soils possess different abilities to inhibit
avocado root rot caused by Phythophthora cinnamomi. Analysis of the two rDNA
clone libraries revealed differences in the two fungal communities. It also
revealed a markedly different depiction of the soil fungal community than that
generated by a culture-based analysis, confirming the value of rDNA-based
approaches for identifying organisms that may not readily grow on agar media.
Additional evidence of the usefulness of the primers was obtained by identifying
fungi associated with avocado leaves. In both the soil and leaf analyses, no
nonfungal rDNA sequences were identified, illustrating the selectivity of these
PCR primers. This work demonstrates the ability of two newly developed PCR primer
sets to amplify fungal rDNA from soil and plant tissue, thereby providing unique
tools to examine this vast and mostly undescribed community of organisms.
PMID- 11010883
TI - Bacterial functional redundancy along a soil reclamation gradient.
AB - A strategy to measure bacterial functional redundancy was developed and tested
with soils collected along a soil reclamation gradient by determining the
richness and diversity of bacterial groups capable of in situ growth on selected
carbon substrates. Soil cores were collected from four sites along a transect
from the Jamari tin mine site in the Jamari National Forest, Rondonia, RO,
Brazil: denuded mine spoil, soil from below the canopy of invading pioneer trees,
revegetated soil under new growth on the forest edge, and the forest floor of an
adjacent preserved forest. Bacterial population responses were analyzed by
amending these soil samples with individual carbon substrates in the presence of
bromodeoxyuridine (BrdU). BrdU-labeled DNA was then subjected to a 16S-23S rRNA
intergenic analysis to depict the actively growing bacteria from each site. The
number and diversity of bacterial groups responding to four carbon substrates (L
serine, L-threonine, sodium citrate, and alpha-lactose hydrate) increased along
the reclamation-vegetation gradient such that the preserved forest soil samples
contained the highest functional redundancy for each substrate. These data
suggest that bacterial functional redundancy increases in relation to the
regrowth of plant communities and may therefore represent an important aspect of
the restoration of soil biological functionality to reclaimed mine spoils. They
also suggest that bacterial functional redundancy may be a useful indicator of
soil quality and ecosystem functioning.
PMID- 11010884
TI - Antisense downregulation of sigma(32) as a transient metabolic controller in
Escherichia coli: effects on yield of active organophosphorus hydrolase.
AB - Plasmids containing an antisense fragment of the sigma(32) gene were constructed
and introduced into Escherichia coli cells. Downregulation of the sigma(32)
mediated stress response was evaluated under heat shock and ethanol stress and
during the production of organophosphorus hydrolase (OPH). Northern blot analyses
revealed that sigma(32) sense mRNA was virtually undetected in antisense
producing cultures from 5 to 20 min after antisense induction. However, lower
molecular-weight bands were found, presumably due to partial degradation of
sigma(32) mRNA. While a >10-fold increase in sigma(32) protein level was found
under ethanol stress in the control cultures, antisense producing cultures
resulted in a <3-fold increase, indicating downregulation of sigma(32).
Correspondingly, antisense synthesis resulted in a decreased level of a sigma(32)
regulated chaperone (GroEL) for the first 2 h after induction relative to control
cultures without sigma(32) antisense mRNA. The total yield of OPH in the presence
of sigma(32) antisense was, on average, 62% of the yield without antisense.
However, during sigma(32) antisense production, a sixfold-higher specific OPH
activity was observed compared to non-antisense-producing cultures.
PMID- 11010885
TI - Bacterial origin and community composition in the barley phytosphere as a
function of habitat and presowing conditions.
AB - An understanding of the factors influencing colonization of the rhizosphere is
essential for improved establishment of biocontrol agents. The aim of this study
was to determine the origin and composition of bacterial communities in the
developing barley (Hordeum vulgare) phytosphere, using denaturing gradient gel
electrophoresis (DGGE) analysis of 16S rRNA genes amplified from extracted DNA.
Discrete community compositions were identified in the endorhizosphere,
rhizoplane, and rhizosphere soil of plants grown in an agricultural soil for up
to 36 days. Cluster analysis revealed that DGGE profiles of the rhizoplane more
closely resembled those in the soil than the profiles found in the root tissue or
on the seed, suggesting that rhizoplane bacteria primarily originated from the
surrounding soil. No change in bacterial community composition was observed in
relation to plant age. Pregermination of the seeds for up to 6 days improved the
survival of seed-associated bacteria on roots grown in soil, but only in the
upper, nongrowing part of the rhizoplane. The potential occurrence of skewed PCR
amplification was examined, and only minor cases of PCR bias for mixtures of two
different DNA samples were observed, even when one of the samples contained plant
DNA. The results demonstrate the application of culture-independent, molecular
techniques in assessment of rhizosphere bacterial populations and the importance
of the indigenous soil population in colonization of the rhizosphere.
PMID- 11010886
TI - PCR-based identification of MAT-1 and MAT-2 in the Gibberella fujikuroi species
complex.
AB - All sexually fertile strains in the Gibberella fujikuroi species complex are
heterothallic, with individual mating types conferred by the broadly conserved
ascomycete idiomorphs MAT-1 and MAT-2. We sequenced both alleles from all eight
mating populations, developed a multiplex PCR technique to distinguish these
idiomorphs, and tested it with representative strains from all eight biological
species and 22 additional species or phylogenetic lineages from this species
complex. In most cases, either an approximately 800-bp fragment from MAT-2 or an
approximately 200-bp fragment from MAT-1 is amplified. The amplified fragments
cosegregate with mating type, as defined by sexual cross-fertility, in a cross of
Fusarium moniliforme (Fusarium verticillioides). Neither of the primer pairs
amplify fragments from Fusarium species such as Fusarium graminearum, Fusarium
pseudograminearum, and Fusarium culmorum, which have, or are expected to have,
Gibberella sexual stages but are thought to be relatively distant from the
species in the G. fujikuroi species complex. Our results suggest that MAT allele
sequences are useful indicators of phylogenetic relatedness in these and other
Fusarium species.
PMID- 11010887
TI - Concentration and detection of caliciviruses in water samples by reverse
transcription-PCR.
AB - Human caliciviruses (HuCVs) cause waterborne outbreaks of gastroenteritis.
Standard indicators of a safe water supply do not adequately predict
contamination of water by viruses, including HuCVs. We developed a method to
concentrate and detect HuCVs in water samples by using a cultivable primate
calicivirus (Pan-1) as a model. Viable Pan-1 was seeded in different types of
water and then filtered with a 1MDS filter, eluted with beef extract (BE), and
reconcentrated by polyethylene glycol (PEG) precipitation. The viruses in the
final samples were tested by plaque assay or by reverse transcription (RT)-PCR
following extraction of the RNA with Trizol. Pan-1 was more sensitive to high-pH
treatment than poliovirus was; a pH 9.0 BE solution was found to recover 35% more
viable Pan-1 than a pH 9.5 BE solution recovered. Pan-1 was recovered from small
volumes of deionized, finished, ground, and surface waters at efficiencies of 94,
73, 67, and 64%, respectively, when samples were assayed after elution without
further concentration. When larger volumes of water (up to 40 liters) were tested
after elution and concentration with PEG, 38, 19, and 14% of the seeded Pan-1
were recovered from finished, ground, and surface waters, respectively. The limit
of detection of Pan-1 by RT-PCR was estimated to be 0.75 to 1.5 PFU in 40 liters
of finished water. This method may be adapted for monitoring HuCVs in drinking
water and other types of water for public health safety.
PMID- 11010888
TI - Bacterial phosphating of mild (unalloyed) steel.
AB - Mild (unalloyed) steel electrodes were incubated in phosphate-buffered cultures
of aerobic, biofilm-forming Rhodococcus sp. strain C125 and Pseudomonas putida
mt2. A resulting surface reaction leading to the formation of a corrosion
inhibiting vivianite layer was accompanied by a characteristic electrochemical
potential (E) curve. First, E increased slightly due to the interaction of
phosphate with the iron oxides covering the steel surface. Subsequently, E
decreased rapidly and after 1 day reached -510 mV, the potential of free iron,
indicating the removal of the iron oxides. At this point, only scattered patches
of bacteria covered the surface. A surface reaction, in which iron was released
and vivianite precipitated, started. E remained at -510 mV for about 2 days,
during which the vivianite layer grew steadily. Thereafter, E increased markedly
to the initial value, and the release of iron stopped. Changes in E and formation
of vivianite were results of bacterial activity, with oxygen consumption by the
biofilm being the driving force. These findings indicate that biofilms may
protect steel surfaces and might be used as an alternative method to combat
corrosion.
PMID- 11010889
TI - Identification of collagen-binding proteins in Lactobacillus spp. with surface
enhanced laser desorption/ionization-time of flight ProteinChip technology.
AB - Biosurfactants produced by Lactobacillus fermentum RC-14, L. rhamnosus GR-1 and
36, and L. casei Shirota were found to contain proteins that bind to both
collagen types III and VI, as determined by surface-enhanced laser
desorption/ionization (SELDI)-time of flight mass spectrometry. Both collagen
types III and VI immobilized on SELDI preactivated ProteinChip arrays detected
several different sizes (2 to 48 kDa) of collagen-binding proteins. Overall, the
RC-14-produced biosurfactant contained the greatest number of collagen-binding
proteins (RC-14 > GR-1 > 36 > Shirota), including the mature form of a previously
cloned 29-kDa collagen-binding protein (referred to in its mature 26-kDa form).
Although biosurfactants isolated from L. casei Shirota and L. rhamnosus 36 and GR
1 also contain several collagen-binding proteins, they do not contain the 26-kDa
collagen-binding protein. Together, these results demonstrate the utility of the
SELDI system as a means of rapidly characterizing clinically important but
complex biosurfactant solutions.
PMID- 11010890
TI - Field evaluation of a semiautomated method for rapid and simple analysis of
recreational water microbiological quality.
AB - An early warning system using a rapid enzymatic semiautomated method suitable for
fecal coliform detection in recreational waters within 8 h was developed further
and evaluated in this study. This rapid method was compared to the standard
method followed in the United Kingdom. We used 1,011 samples originating from 206
different locations in Wales. When we assessed the presence or absence of fecal
coliforms, targeting very low levels of contamination, we obtained 83.9%
agreement between the rapid method and the lauryl sulfate broth-membrane
filtration technique, whereas direct confirmation of the samples processed by the
rapid method showed 89. 3% agreement. Environmental enzymatic background activity
was found to be the main limiting factor for this method. Owing to a specific and
integrated handling of the results by the software of the instrument, the
percentage of false-positive results (a consequence of enzymatic background) was
successfully limited to 2.9% by the direct confirmation evaluation. However, 7.8%
false-negative results due to "late-growers" had to be accepted in order to
produce results within a working day. At present, the method can be used in a
more conservative way to assess the environmental threshold of 100 CFU of fecal
coliforms per 100 ml in recreational waters. The implications of our findings
with regard to the applicability of rapid enzymatic methods are discussed.
PMID- 11010891
TI - Correlations between morphological, molecular biological, and physiological
characteristics in clinical and nonclinical isolates of Acanthamoeba spp.
AB - Eleven Acanthamoeba isolates, obtained from Acanthamoeba keratitis patients, from
contact lens cases of non-Acanthamoeba keratitis patients, from asymptomatic
individuals, from necrotic tissue, and from tap water and two reference strains
were investigated by morphological, molecular biological, and physiological means
in order to discriminate clinically relevant and nonrelevant isolates. All
clinically relevant isolates showed Acanthamoeba sp. group II morphology. 18S
ribosomal DNA sequencing revealed sequence type T4 to be the most prevalent group
among the isolates and also the group recruiting most of the pathogenic strains.
Interestingly, within T4 the strains of no clinical relevance clustered together.
Moreover, physiological properties appeared to be highly consistent with initial
pathogenicity and with sequence clustering. Altogether, the results of our study
indicate a correlation between the phylogenetic relationship and pathogenicity.
PMID- 11010892
TI - Vesicle-mediated transfer of virulence genes from Escherichia coli O157:H7 to
other enteric bacteria.
AB - Membrane vesicles are released from the surfaces of many gram-negative bacteria
during growth. Vesicles consist of proteins, lipopolysaccharide, phospholipids,
RNA, and DNA. Results of the present study demonstrate that membrane vesicles
isolated from the food-borne pathogen Escherichia coli O157:H7 facilitate the
transfer of genes, which are then expressed by recipient Salmonella enterica
serovar Enteritidis or E. coli JM109. Electron micrographs of purified DNA from
E. coli O157:H7 vesicles showed large rosette-like structures, linear DNA
fragments, and small open-circle plasmids. PCR analysis of vesicle DNA
demonstrated the presence of specific genes from host and recombinant plasmids
(hly, L7095, mobA, and gfp), chromosomal DNA (uidA and eaeA), and phage DNA (stx1
and stx2). The results of PCR and the Vero cell assay demonstrate that genetic
material, including virulence genes, is transferred to recipient bacteria and
subsequently expressed. The cytotoxicity of the transformed enteric bacteria was
sixfold higher than that of the parent isolate (E. coli JM109). Utilization of
the nonhost plasmid (pGFP) permitted the evaluation of transformation efficiency
(ca. 10(3) transformants microg of DNA(-1)) and demonstrated that vesicles can
deliver antibiotic resistance. Transformed E. coli JM109 cells were resistant to
ampicillin and fluoresced a brilliant green. The role vesicles play in genetic
exchange between different species in the environment or host has yet to be
defined.
PMID- 11010893
TI - MET17 and hydrogen sulfide formation in Saccharomyces cerevisiae.
AB - Commercial isolates of Saccharomyces cerevisiae differ in the production of
hydrogen sulfide (H(2)S) during fermentation, which has been attributed to
variation in the ability to incorporate reduced sulfur into organic compounds. We
transformed two commercial strains (UCD522 and UCD713) with a plasmid
overexpressing the MET17 gene, which encodes the bifunctional O-acetylserine/O
acetylhomoserine sulfhydrylase (OAS/OAH SHLase), to test the hypothesis that the
level of activity of this enzyme limits reduced sulfur incorporation, leading to
H(2)S release. Overexpression of MET17 resulted in a 10- to 70-fold increase in
OAS/OAH SHLase activity in UCD522 but had no impact on the level of H(2)S
produced. In contrast, OAS/OAH SHLase activity was not as highly expressed in
transformants of UCD713 (0.5- to 10-fold) but resulted in greatly reduced H(2)S
formation. Overexpression of OAS/OAH SHLase activity was greater in UCD713 when
grown under low-nitrogen conditions, but the impact on reduction of H(2)S was
greater under high-nitrogen conditions. Thus, there was not a good correlation
between the level of enzyme activity and H(2)S production. We measured cellular
levels of cysteine to determine the impact of overexpression of OAS/OAH SHLase
activity on sulfur incorporation. While Met17p activity was not correlated with
increased cysteine production, conditions that led to elevated cytoplasmic levels
of cysteine also reduced H(2)S formation. Our data do not support the simple
hypothesis that variation in OAS/OAH SHLase activity is correlated with H(2)S
production and release.
PMID- 11010894
TI - Adaptation of the nisin-controlled expression system in Lactobacillus plantarum:
a tool to study in vivo biological effects.
AB - The potential of lactic acid bacteria as live vehicles for the production and
delivery of therapeutic molecules is being actively investigated today. For
future applications it is essential to be able to establish dose-response curves
for the targeted biological effect and thus to control the production of a
heterologous biopeptide by a live lactobacillus. We therefore implemented in
Lactobacillus plantarum NCIMB8826 the powerful nisin-controlled expression (NICE)
system based on the autoregulatory properties of the bacteriocin nisin, which is
produced by Lactococcus lactis. The original two-plasmid NICE system turned out
to be poorly suited to L. plantarum. In order to obtain a stable and reproducible
nisin dose-dependent synthesis of a reporter protein (beta-glucuronidase) or a
model antigen (the C subunit of the tetanus toxin, TTFC), the lactococcal nisRK
regulatory genes were integrated into the chromosome of L. plantarum NCIMB8826.
Moreover, recombinant L. plantarum producing increasing amounts of TTFC was used
to establish a dose-response curve after subcutaneous administration to mice. The
induced serum immunoglobulin G response was correlated with the dose of antigen
delivered by the live lactobacilli.
PMID- 11010895
TI - Possible interactions within a methanotrophic-heterotrophic groundwater community
able to transform linear alkylbenzenesulfonates.
AB - The relationships and interactions within a methanotrophic-heterotrophic
groundwater community were studied in a closed system (shake culture) in the
presence of methane as the primary carbon and energy source and with the addition
of the pure linear alkylbenzenesulfonate (LAS) congener 2-[4-(sulfophenyl)]decan
as a cometabolic substrate. When cultured under different conditions, this
community was shown to be a stable association, consisting of one obligate type
II methanotroph and four or five heterotrophs possessing different nutritional
and physiological characteristics. The results of experiments examining growth
kinetics and nutritional relationships suggested that a number of complex
interactions existed in the community in which the methanotroph was the only
member able to grow on methane and to cometabolically initiate LAS
transformation. These growth and metabolic activities of the methanotroph ensured
the supply of a carbon source and specific nutrients which sustained the growth
of four or five heterotrophs. In addition to the obligatory nutritional
relationships between the methanotroph and heterotrophs, other possible
interactions resulted in the modification of basic growth parameters of
individual populations and a concerted metabolic attack on the complex LAS
molecule. Most of these relationships conferred beneficial effects on the
interacting populations, making the community adaptable to various environmental
conditions and more efficient in LAS transformation than any of the individual
populations alone.
PMID- 11010896
TI - Identification and analysis of the polyhydroxyalkanoate-specific beta
ketothiolase and acetoacetyl coenzyme A reductase genes in the cyanobacterium
Synechocystis sp. strain PCC6803.
AB - Synechocystis sp. strain PCC6803 possesses a polyhydroxyalkanoate (PHA)-specific
beta-ketothiolase encoded by phaA(Syn) and an acetoacetyl-coenzyme A (CoA)
reductase encoded by phaB(Syn). A similarity search of the entire Synechocystis
genome sequence identified a cluster of two putative open reading frames (ORFs)
for these genes, slr1993 and slr1994. Sequence analysis showed that the ORFs
encode proteins having 409 and 240 amino acids, respectively. The two ORFs are
colinear and most probably coexpressed, as revealed by sequence analysis of the
promoter regions. Heterologous transformation of Escherichia coli with the two
genes and the PHA synthase of Synechocystis resulted in accumulation of PHAs that
accounted for up to 12.3% of the cell dry weight under high-glucose growth
conditions. Targeted disruption of the above gene cluster in Synechocystis
eliminated the accumulation of PHAs. ORFs slr1993 and slr1994 thus encode the PHA
specific beta-ketothiolase and acetoacetyl-CoA reductase of Synechocystis and,
together with the recently characterized PHA synthase genes in this organism (S.
Hein, H. Tran, and A. Steinbuchel, Arch. Microbiol. 170:162-170, 1998), form the
first complete PHA biosynthesis pathway known in cyanobacteria. Sequence
alignment of all known short-chain-length PHA-specific acetoacetyl-CoA reductases
also suggests an extended signature sequence, VTGXXXGIG, for this group of
proteins. Phylogenetic analysis further places the origin of phaA(Syn) and
phaB(Syn) in the gamma subdivision of the division Proteobacteria.
PMID- 11010897
TI - Molecular genetic manipulation of truncated Cry1C protein synthesis in Bacillus
thuringiensis to improve stability and yield.
AB - Cry1 protoxins of Bacillus thuringiensis are insecticidal 135-kDa proteins
synthesized and assembled into parasporal crystals during sporulation. After
ingestion, these crystals dissolve in the midgut and active toxins with molecular
masses of about 65-kDa are released from the N-terminal half of the molecule by
midgut proteases. Direct synthesis of the toxin-containing N-terminal half of
Cry1 molecules using recombinant DNA techniques results in a low level of
unstable truncated proteins that do not crystallize. In the present study,
inclusions of truncated Cry1C (Cry1C-t) were obtained by combining genetic
elements from other endotoxin genes and operons that enhance Cry protein
synthesis and crystallization. Increased levels of Cry1C-t synthesis were
achieved by using cyt1A promoters to drive expression of the 5' half of cry1C
that included in the construct the 5' cry3A STAB-SD mRNA stabilizing sequence and
the 3' stem-loop transcription terminator. RNA dot blot analysis showed that the
STAB-SD and 3' transcriptional termination sequences were important for
stabilization of truncated cry1C (cry1C-t) mRNA. A low level of cry1C-t mRNA was
present when only the cyt1A promoters were used to express cry1C-t, but no
accumulation of Cry1C-t was detected in Western blots. The orientation of the
transcription terminator was important to enhancing Cry1C-t synthesis. Inclusion
of the 20- and 29-kDa helper protein genes in cry1C-t constructs further enhanced
synthesis. The Cry1C-t protein was toxic to Spodoptera exigua larvae, though the
toxicity (50% lethal concentration [LC(50)] = 13.2 microg/ml) was lower than that
of full-length Cry1C (LC(50) = 1.8 microg/ml). However, transformation of the HD1
isolate of B. thuringiensis subsp. kurstaki with the cry1C-t construct enhanced
its toxicity to S. exigua as much as fourfold.
PMID- 11010898
TI - Internal trehalose protects endocytosis from inhibition by ethanol in
Saccharomyces cerevisiae.
AB - Endocytosis in Saccharomyces cerevisiae is inhibited by concentrations of ethanol
of 2 to 6% (vol/vol), which are lower than concentrations commonly present in its
natural habitats. In spite of this inhibition, endocytosis takes place under
enological conditions when high concentrations of ethanol are present. Therefore,
it seems that yeast has developed some means to circumvent the inhibition. In
this work we have investigated this possibility. We identified two stress
conditions under which endocytosis was resistant to inhibition by ethanol:
fermentation during nitrogen starvation and growth on nonfermentable substrates.
Under these conditions, yeast accumulates stress protectors, primarily trehalose
and Hsp104, a protein required for yeast to survive ethanol stress. We found the
following. (i) The appearance of ethanol resistance was accompanied by trehalose
accumulation. (ii) Mutant cells unable to synthesize trehalose also were unable
to develop resistance. (iii) Mutant cells that accumulated trehalose during
growth on sugars were resistant to ethanol even under this nonstressing
condition. (iv) Mutant cells unable to synthesize Hsp104 were able to develop
resistance. We conclude that trehalose is the major factor in the protection of
endocytosis from ethanol. Our results suggest another important physiological
role for trehalose in yeast.
PMID- 11010899
TI - Microbial degradation of the multiply branched alkane 2,6,10,15,19, 23
hexamethyltetracosane (Squalane) by Mycobacterium fortuitum and Mycobacterium
ratisbonense.
AB - Among several bacterial species belonging to the general Gordonia, Mycobacterium,
Micromonospora, Pseudomonas, and Rhodococcus, only two mycobacterial isolates,
Mycobacterium fortuitum strain NF4 and the new isolate Mycobacterium ratisbonense
strain SD4, which was isolated from a sewage treatment plant, were capable of
utilizing the multiply branched hydrocarbon squalane (2,6,10,15,19, 23
hexamethyltetracosane) and its analogous unsaturated hydrocarbon squalene as the
sole carbon source for growth. Detailed degradation studies and high-pressure
liquid chromatography analysis showed a clear decrease of the concentrations of
squalane and squalene during biomass increase. These results were supported by
resting-cell experiments using strain SD4 and squalane or squalene as the
substrate. The degradation of acyclic isoprenoids and alkanes as well as of acids
derived from these compounds was also investigated. Inhibition of squalane and
squalene degradation by acrylic acid indicated the possible involvement of beta
oxidation in the degradation route. To our knowledge, this is the first report
demonstrating the biodegradation of squalane by using defined axenic cultures.
PMID- 11010901
TI - PCR assays that identify the grapevine dieback fungus Eutypa lata.
AB - Eutypa lata is the causal fungal agent of Eutypa dieback, a serious grapevine
necrotic disease. The erratic and delayed (1 to 2 months) appearance of
characteristic conidia on culture media and the presence of numerous
microorganisms in decaying wood make it difficult either to identify or to detect
E. lata in grapevine wood samples. We designed six pairs of PCR primers for
diagnosis of E. lata. Three primer pairs were derived from ribosomal DNA internal
transcribed spacer sequences, and three pairs were derived from randomly
amplified polymorphic DNA fragments. The six primer pairs could be used to
amplify DNAs extracted from all of the E. lata isolates tested. They did not
amplify DNAs from fungi and bacteria representing more than 50 different species
of microorganisms associated with grapevine. We developed a simple protocol,
leading to a rapid release of DNA, that enabled us to identify E. lata from pure
or mixed cultures as well as from grapevine wood samples. Identification of E.
lata in wood was achieved within a few hours, instead of the several weeks
required for classical cultures on agar medium. We believe that the procedure
described here can be adapted to detect other microorganisms involved in woody
plant diseases.
PMID- 11010900
TI - Geographical segregation of the neurotoxin-producing cyanobacterium Anabaena
circinalis.
AB - Blooms of the cyanobacterium Anabaena circinalis are a major worldwide problem
due to their production of a range of toxins, in particular the neurotoxins
anatoxin-a and paralytic shellfish poisons (PSPs). Although there is a worldwide
distribution of A. circinalis, there is a geographical segregation of neurotoxin
production. American and European isolates of A. circinalis produce only anatoxin
a, while Australian isolates exclusively produce PSPs. The reason for this
geographical segregation of neurotoxin production by A. circinalis is unknown.
The phylogenetic structure of A. circinalis was determined by analyzing 16S rRNA
gene sequences. A. circinalis was found to form a monophyletic group of
international distribution. However, the PSP- and non-PSP-producing A. circinalis
formed two distinct 16S rRNA gene clusters. A molecular probe was designed,
allowing the identification of A. circinalis from cultured and uncultured
environmental samples. In addition, probes targeting the predominantly PSP
producing or non-PSP-producing clusters were designed for the characterization of
A. circinalis isolates as potential PSP producers.
PMID- 11010902
TI - Commensal interactions in a dual-species biofilm exposed to mixed organic
compounds.
AB - There is limited knowledge of interspecies interactions in biofilm communities.
In this study, Pseudomonas sp. strain GJ1, a 2-chloroethanol (2-CE)-degrading
organism, and Pseudomonas putida DMP1, a p-cresol-degrading organism, produced
distinct biofilms in response to model mixed waste streams composed of 2-CE and
various p-cresol concentrations. The two organisms maintained a commensal
relationship, with DMP1 mitigating the inhibitory effects of p-cresol on GJ1. A
triple-labeling technique compatible with confocal microscopy was used to
investigate the influence of toxicant concentrations on biofilm morphology,
species distribution, and exopolysaccharide production. Single-species biofilms
of GJ1 shifted from loosely associated cell clusters connected by
exopolysaccharide to densely packed structures as the p-cresol concentrations
increased, and biofilm formation was severely inhibited at high p-cresol
concentrations. In contrast, GJ1 was abundant when associated with DMP1 in a dual
species biofilm at all p-cresol concentrations, although at high p-cresol
concentrations it was present only in regions of the biofilm where it was
surrounded by DMP1. Evidence in support of a commensal relationship between DMP1
and GJ1 was obtained by comparing GJ1-DMP1 biofilms with dual-species biofilms
containing GJ1 and Escherichia coli ATCC 33456, an adhesive strain that does not
mineralize p-cresol. Additionally, the data indicated that only tower-like cell
structures in the GJ1-DMP1 biofilm produced exopolysaccharide, in contrast to the
uniform distribution of EPS in the single-species GJ1 biofilm.
PMID- 11010903
TI - Development of a vital fluorescent staining method for monitoring bacterial
transport in subsurface environments.
AB - Previous bacterial transport studies have utilized fluorophores which have been
shown to adversely affect the physiology of stained cells. This research was
undertaken to identify alternative fluorescent stains that do not adversely
affect the transport or viability of bacteria. Initial work was performed with a
groundwater isolate, Comamonas sp. strain DA001. Potential compounds were first
screened to determine staining efficiencies and adverse side effects. 5-(And 6-)
carboxyfluorescein diacetate, succinimidyl ester (CFDA/SE) efficiently stained
DA001 without causing undesirable effects on cell adhesion or viability. Members
of many other gram-negative and gram-positive bacterial genera were also
effectively stained with CFDA/SE. More than 95% of CFDA/SE-stained Comamonas sp.
strain DA001 cells incubated in artificial groundwater (under no-growth
conditions) remained fluorescent for at least 28 days as determined by
epifluorescent microscopy and flow cytometry. No differences in the survival and
culturability of CFDA/SE-stained and unstained DA001 cells in groundwater or
saturated sediment microcosms were detected. The bright, yellow-green cells were
readily distinguished from autofluorescing sediment particles by epifluorescence
microscopy. A high throughput method using microplate spectrofluorometry was
developed, which had a detection limit of mid-10(5) CFDA-stained cells/ml; the
detection limit for flow cytometry was on the order of 1,000 cells/ml. The
results of laboratory-scale bacterial transport experiments performed with intact
sediment cores and nondividing DA001 cells revealed good agreement between the
aqueous cell concentrations determined by the microplate assay and those
determined by other enumeration methods. This research indicates that CFDA/SE is
very efficient for labeling cells for bacterial transport experiments and that it
may be useful for other microbial ecology research as well.
PMID- 11010904
TI - Metabolic engineering of an aerobic sulfate reduction pathway and its application
to precipitation of cadmium on the cell surface.
AB - The conversion of sulfate to an excess of free sulfide requires stringent
reductive conditions. Dissimilatory sulfate reduction is used in nature by
sulfate-reducing bacteria for respiration and results in the conversion of
sulfate to sulfide. However, this dissimilatory sulfate reduction pathway is
inhibited by oxygen and is thus limited to anaerobic environments. As an
alternative, we have metabolically engineered a novel aerobic sulfate reduction
pathway for the secretion of sulfides. The assimilatory sulfate reduction pathway
was redirected to overproduce cysteine, and excess cysteine was converted to
sulfide by cysteine desulfhydrase. As a potential application for this pathway, a
bacterium was engineered with this pathway and was used to aerobically
precipitate cadmium as cadmium sulfide, which was deposited on the cell surface.
To maximize sulfide production and cadmium precipitation, the production of
cysteine desulfhydrase was modulated to achieve an optimal balance between the
production and degradation of cysteine.
PMID- 11010905
TI - Detection and identification of bacterial endosymbionts in arbuscular mycorrhizal
fungi belonging to the family Gigasporaceae.
AB - Intracellular bacteria have been found previously in one isolate of the
arbuscular mycorrhizal (AM) fungus Gigaspora margarita BEG 34. In this study, we
extended our investigation to 11 fungal isolates obtained from different
geographic areas and belonging to six different species of the family
Gigasporaceae. With the exception of Gigaspora rosea, isolates of all of the AM
species harbored bacteria, and their DNA could be PCR amplified with universal
bacterial primers. Primers specific for the endosymbiotic bacteria of BEG 34
could also amplify spore DNA from four species. These specific primers were
successfully used as probes for in situ hybridization of endobacteria in G.
margarita spores. Neighbor-joining analysis of the 16S ribosomal DNA sequences
obtained from isolates of Scutellospora persica, Scutellospora castanea, and G.
margarita revealed a single, strongly supported branch nested in the genus
Burkholderia.
PMID- 11010906
TI - A fruiting body tissue method for efficient Agrobacterium-mediated transformation
of Agaricus bisporus.
AB - We describe a modified Agrobacterium-mediated method for the efficient
transformation of Agaricus bisporus. Salient features of this procedure include
cocultivation of Agrobacterium and fruiting body gill tissue and use of a vector
with a homologous promoter. This method offers new prospects for the genetic
manipulation of this commercially important mushroom species.
PMID- 11010907
TI - Bacterial activity in South Pole snow.
AB - Large populations (200 to 5,000 cells ml(-1) in snowmelt) of bacteria were
present in surface snow and firn from the south pole sampled in January 1999 and
2000. DNA isolated from this snow yielded ribosomal DNA sequences similar to
those of several psychrophilic bacteria and a bacterium which aligns closely with
members of the genus Deinococcus, an ionizing-radiation- and desiccation
resistant genus. We also obtained evidence of low rates of bacterial DNA and
protein synthesis which indicates that the organisms were metabolizing at ambient
subzero temperatures (-12 to -17 degrees C).
PMID- 11010908
TI - Use of combined microautoradiography and fluorescence in situ hybridization to
determine carbon metabolism in mixed natural communities of uncultured bacteria
from the genus Achromatium.
AB - Combined microautoradiography and fluorescence in situ hybridization (FISH) was
used to investigate carbon metabolism in uncultured bacteria from the genus
Achromatium. All of the Achromatium species identified in a freshwater sediment
from Rydal Water, Cumbria, United Kingdom, which were distinguishable only by
FISH, assimilated both [(14)C]bicarbonate and [(14)C]acetate. This extends
previous findings that Achromatium spp. present at another location could only
utilize organic carbon sources. Achromatium spp., therefore, probably exhibit a
range of physiologies, i.e., facultative chemolithoautotrophy, mixotrophy, and
chemoorganoheterotrophy, similar to other large sulfur bacteria (e.g., Beggiatoa
spp.).
PMID- 11010909
TI - Development of 16S rRNA-based probes for the Coriobacterium group and the
Atopobium cluster and their application for enumeration of Coriobacteriaceae in
human feces from volunteers of different age groups.
AB - Two 16S rRNA-targeted probes were developed: one for the Coriobacterium group and
the other for the Atopobium cluster (which comprises most of the
Coriobacteriaceae species, including the Coriobacterium group). The new probes
were based on sequences of three new Coriobacteriaceae strains isolated from
human feces and clinical material and sequences from databases. Application of
the probes to fecal samples showed that formula-fed infants had higher numbers of
Coriobacterium group cells in their feces than breast-fed infants. In addition,
based on the presented results, it is hypothesized that with the increasing age
of a person, the diversity of Atopobium cluster species present in the feces
increases.
PMID- 11010910
TI - Cometabolic degradation of dibenzofuran by biphenyl-cultivated Ralstonia sp.
strain SBUG 290.
AB - Cells of the gram-negative bacterium Ralstonia sp. strain SBUG 290 grown in the
presence of biphenyl are able to cooxidize dibenzofuran which has been 1,2
hydroxylated. Meta cleavage of the 1, 2-dihydroxydibenzofuran between carbon
atoms 1 and 9b produced 2-hydroxy-4-(3'-oxo-3'H-benzofuran-2'-yliden)but-2-enoic
acid, which was degraded completely via salicylic acid. The presence of these
intermediates indicates a degradation mechanism for dibenzofuran via lateral
dioxygenation by Ralstonia sp. strain SBUG 290.
PMID- 11010911
TI - Pacific Northwest marine sediments contain ammonia-oxidizing bacteria in the beta
subdivision of the Proteobacteria.
AB - The diversity of ammonia-oxidizing bacteria in aquatic sediments was studied by
retrieving ammonia monooxygenase and methane monooxygenase gene sequences.
Methanotrophs dominated freshwater sediments, while beta-proteobacterial ammonia
oxidizers dominated marine sediments. These results suggest that gamma
proteobacteria such as Nitrosococcus oceani are minor members of marine sediment
ammonia-oxidizing communities.
PMID- 11010912
TI - Sulfur regulation of the sulfate transporter genes sutA and sutB in Penicillium
chrysogenum.
AB - Penicillium chrysogenum uses sulfate as a source of sulfur for the biosynthesis
of penicillin. Sulfate uptake and the mRNA levels of the sulfate transporter
encoding sutB and sutA genes are all reduced by high sulfate concentrations and
are elevated by sulfate starvation. In a high-penicillin-yielding strain, sutB is
effectively transcribed even in the presence of excess sulfate. This deregulation
may facilitate the efficient incorporation of sulfur into cysteine and
penicillin.
PMID- 11010913
TI - Improved template preparation for PCR-based assays for detection of food-borne
bacterial pathogens.
AB - Shigella flexneri, Salmonella enterica serotype Typhimurium, and Listeria
monocytogenes were applied to FTA filters, and the filters were used directly as
templates to demonstrate their sensitivity and applicability in PCR-based
detection assays. With pure cultures, the sensitivities of detection by FTA
filter-based PCR were 30 to 50 and 200 CFU for the gram-negative enterics and
Listeria, respectively. Different numbers of S. flexneri cells were used in
controlled contamination experiments with several different foods (produce, beef,
and apple cider). Aliquots from concentrated food washes subsequently spotted
onto FTA filters and assayed by PCR gave consistently positive results and
detection limits similar to those observed with pure-culture dilutions. This
universal method for PCR template preparation from bacterial cells is rapid and
highly sensitive and reduces interference from food-associated inhibitors of PCR.
In addition, its broad applicability eliminates the need for multiple methods for
analysis of food matrices.
PMID- 11010914
TI - Microscale diversity of the genus Nitrobacter in soil on the basis of analysis of
genes encoding rRNA.
AB - We looked at the diversity of [NO(2)](-) oxidizers at field scale by examining
isolates at clump scale and in microsamples of soil (diameter, 50 microm). The
genetic distances (as determined by amplified ribosomal DNA restriction analysis
performed with Nitrobacter-specific primers) in a small clump of soil were as
large as those between reference strains from large geographical areas. Diversity
in individual microsamples was shown by serotyping.
PMID- 11010915
TI - The presence of humic substances and DNA in RNA extracts affects hybridization
results.
AB - RNA extracts obtained from environmental samples are frequently contaminated with
coextracted humic substances and DNA. It was demonstrated that the response in
rRNA-targeted oligonucleotide probe hybridizations decreased as the
concentrations of humic substances and DNA in RNA extracts increased. The
decrease in hybridization signal in the presence of humic substances appeared to
be due to saturation of the hybridization membrane with humic substances,
resulting in a lower amount of target rRNA bound to the membrane. The decrease in
hybridization response in the presence of low amounts of DNA may be the result of
reduced rRNA target accessibility. The presence of high amounts of DNA in RNA
extracts resulted in membrane saturation. Consistent with the observations for
DNA contamination, the addition of poly(A) to RNA extracts, a common practice
used to prepare RNA dilutions for membrane blotting, also reduced hybridization
signals, likely because of reduced target accessibility and membrane saturation
effects.
PMID- 11010916
TI - Rapid and simple determination of the Escherichia coli phylogenetic group.
AB - Phylogenetic analysis has shown that Escherichia coli is composed of four main
phylogenetic groups (A, B1, B2, and D) and that virulent extra-intestinal strains
mainly belong to groups B2 and D. Actually, phylogenetic groups can be determined
by multilocus enzyme electrophoresis or ribotyping, both of which are complex,
time-consuming techniques. We describe a simple and rapid phylogenetic grouping
technique based on triplex PCR. The method, which uses a combination of two genes
(chuA and yjaA) and an anonymous DNA fragment, was tested with 230 strains and
showed excellent correlation with reference methods.
PMID- 11010917
TI - Structure and species composition of mercury-reducing biofilms.
AB - Mercury-reducing biofilms from packed-bed bioreactors treating nonsterile
industrial effluents were shown to consist of a monolayer of bacteria by scanning
electron microscopy. Droplets of several micrometers in diameter which
accumulated outside of the bacterial cells were identified as elemental mercury
by electron-dispersive X-ray analysis. The monospecies biofilms of Pseudomonas
putida Spi3 initially present were invaded by additional strains, which were
identified to the species level by thermogradient gel electrophoresis (TGGE) and
16S rDNA sequencing. TGGE community fingerprints of the biofilms showed that they
were composed of the effluent bacteria and did not contain uncultivable
microorganisms. Of the 13 effluent bacterial strains, 2 were not mercury
resistant, while all the others had resistance levels similar to or higher than
the inoculant strain.
PMID- 11010918
TI - mRNA detection by reverse transcription-PCR for monitoring viability over time in
an Enterococcus faecalis viable but nonculturable population maintained in a
laboratory microcosm.
AB - The viable but nonculturable (VBNC) state is a survival strategy adopted by
bacteria when they are exposed to hostile environmental conditions. It has been
shown that VBNC forms of bacteria are no longer capable of growing on
conventional bacteriological media but conserve pathogenic factors and/or genes.
It is thus necessary to develop methods capable of detecting nonculturable
bacteria and of establishing their viability when the microbiological quality of
environments is monitored. In this study we demonstrated that a gene was
expressed during the VBNC state in a low-nutrient-concentration microcosm through
detection of Enterococcus faecalis pbp5 mRNA by reverse transcription-PCR over a
3-month period. The presence of mRNA correlated with metabolic activity and
resuscitation capability, indicating the viability of the VBNC cells.
PMID- 11010919
TI - Incorporation of protease K into larval insect membrane vesicles does not result
in disruption of integrity or function of the pore-forming Bacillus thuringiensis
delta-endotoxin.
AB - Bacillus thuringiensis delta-endotoxins insert into the brush border membranes of
insect larval cells to form ion channels. A possible interaction of these toxins
with a cytoplasmic component was examined by preloading vesicles from insect
larval cells with protease K followed by incubation with toxin. There was no
evidence for toxin antigens smaller than the intact toxin in extracts of
solubilized vesicles, nor was there an effect of the inclusion of protease K on
either of two functional properties, the formation of toxin aggregates or of ion
pores. These toxins, physically and functionally, appear to be confined to the
membrane.
PMID- 11010920
TI - A PCR assay To discriminate human and ruminant feces on the basis of host
differences in Bacteroides-Prevotella genes encoding 16S rRNA.
AB - Our purpose was to develop a rapid, inexpensive method of diagnosing the source
of fecal pollution in water. In previous research, we identified Bacteroides
Prevotella ribosomal DNA (rDNA) PCR markers based on analysis. These markers
length heterogeneity PCR and terminal restriction fragment length polymorphism
distinguish cow from human feces. Here, we recovered 16S rDNA clones from natural
waters that were close phylogenetic relatives of the markers. From the sequence
data, we designed specific PCR primers that discriminate human and ruminant
sources of fecal contamination.
PMID- 11010921
TI - Phenylacetyl-coenzyme A is the true inducer of the phenylacetic acid catabolism
pathway in Pseudomonas putida U.
AB - Aerobic degradation of phenylacetic acid in Pseudomonas putida U is carried out
by a central catabolism pathway (phenylacetyl-coenzyme A [CoA] catabolon core).
Induction of this route was analyzed by using different mutants specifically
designed for this objective. Our results revealed that the true inducer molecule
is phenylacetyl-CoA and not other structurally or catabolically related aromatic
compounds.
PMID- 11010922
TI - Antisense silencing of the creA gene in Aspergillus nidulans.
AB - Antisense expression of a portion of the gene encoding the major carbon
catabolite repressor CREA in Aspergillus nidulans resulted in a substantial
increase in the levels of glucose-repressible enzymes, both endogenous and
heterologous, in the presence of glucose. The derepression effect was
approximately one-half of that achieved in a null creA mutant. Unlike results for
that mutant, however, growth parameters and colony morphology in the antisense
transformants were not affected.
PMID- 11010923
TI - Cross-resistance of pink bollworm (Pectinophora gossypiella) to Bacillus
thuringiensis toxins.
AB - Two strains of pink bollworm (Pectinophora gossypiella) selected in the
laboratory for resistance to Bacillus thuringiensis toxin Cry1Ac had substantial
cross-resistance to Cry1Aa and Cry1Ab but not to Cry1Bb, Cry1Ca, Cry1Da, Cry1Ea,
Cry1Ja, Cry2Aa, Cry9Ca, H04, or H205. The narrow spectrum of resistance and the
cross-resistance to activated toxin Cry1Ab suggest that reduced binding of toxin
to midgut target sites could be an important mechanism of resistance.
PMID- 11010924
TI - A rhamnolipid biosurfactant reduces cadmium toxicity during naphthalene
biodegradation.
AB - A model cocontaminated system was developed to determine whether a metal
complexing biosurfactant, rhamnolipid, could reduce metal toxicity to allow
enhanced organic biodegradation by a Burkholderia sp. isolated from soil.
Rhamnolipid eliminated cadmium toxicity when added at a 10-fold greater
concentration than cadmium (890 microM), reduced toxicity when added at an
equimolar concentration (89 microM), and had no effect at a 10-fold smaller
concentration (8.9 microM). The mechanism by which rhamnolipid reduces metal
toxicity may involve a combination of rhamnolipid complexation of cadmium and
rhamnolipid interaction with the cell surface to alter cadmium uptake.
PMID- 11010925
TI - A bioluminescent whole-cell reporter for detection of 2, 4-dichlorophenoxyacetic
acid and 2,4-dichlorophenol in soil.
AB - A bioreporter was made containing a tfdRP(DII)-luxCDABE fusion in a modified mini
Tn5 construct. When it was introduced into the chromosome of Ralstonia eutropha
JMP134, the resulting strain, JMP134-32, produced a sensitive bioluminescent
response to 2, 4-dichlorophenoxyacetic acid (2,4-D) at concentrations of 2.0
microM to 5.0 mM. This response was linear (R(2) = 0.9825) in the range of 2.0
microM to 1.1 x 10(2) microM. Saturation occurred at higher concentrations, with
maximal bioluminescence occurring in the presence of approximately 1.2 mM 2,4-D.
A sensitive response was also recorded in the presence of 2,4-dichlorophenol at
concentrations below 1.1 x 10(2) microM; however, only a limited bioluminescent
response was recorded in the presence of 3-chlorobenzoic acid at concentrations
below 1.0 mM. A significant bioluminescent response was also recorded when strain
JMP134-32 was incubated with soils containing aged 2,4-D residues.
PMID- 11010926
TI - Antibacterial activity evaluation of microcin J25 against diarrheagenic
Escherichia coli.
AB - The inhibitory activities of known microcins were evaluated against some
diarrheagenic Escherichia coli strains. Some antibacterial properties of microcin
J25, the most active one, were studied. A rapid two-step purification was
performed. The MIC and the minimum bactericidal concentration of J25 against E.
coli O157:H7 were 1 and 100 microg ml(-1), respectively. A 10(4)-CFU ml(-1)
contamination by this strain was destroyed in milk and meat extract by 6.25
microg of J25 ml(-1) and in half-diluted egg yolk by 50 microg of J25 ml(-1).
PMID- 11010927
TI - It's more than an apple a day: an appropriately processed, plant-centered dietary
pattern may be good for your health.
PMID- 11010928
TI - Colorful cancer prevention: alpha-carotene, lycopene, and lung cancer.
PMID- 11010929
TI - Folate, DNA methylation, and gene expression: factors of nature and nurture.
PMID- 11010930
TI - Differential oxidation of individual dietary fatty acids in humans.
AB - BACKGROUND: Dietary fatty acids that are more prone to oxidation than to storage
may be less likely to lead to obesity. OBJECTIVE: The aim of this study was to
determine the effect of chain length, degree of unsaturation, and stereoisomeric
effects of unsaturation on the oxidation of individual fatty acids in normal
weight men. DESIGN: Fatty acid oxidation was examined in men consuming a weight
maintenance diet containing 40% of energy as fat. After consuming the diet for 1
wk, subjects were fed fatty acids labeled with (13)C in the methyl or carboxyl
position (10 mg/kg body wt). The fatty acids fed in random order were laurate,
palmitate, stearate, oleate, elaidate (the trans isomer of oleate), linoleate,
and linolenate blended in a hot liquid meal. Breath samples were collected for
the next 9 h and the oxidation of each fatty acid was assessed by examining
liberated (13)CO(2) in breath. RESULTS: Cumulative oxidation over the 9-h test
ranged from a high of 41% of the dose for laurate to a low of 13% of the dose for
stearate. Of the 18-carbon fatty acids, linolenate was the most highly oxidized
and linoleate appeared to be somewhat conserved. (13)C recovery in breath from
the methyl-labeled fatty acids was approximately 30% less than that from the
carboxyl-labeled fatty acids. CONCLUSIONS: In summary, lauric acid is highly
oxidized, whereas the polyunsaturated and monounsaturated fatty acids are fairly
well oxidized. Oxidation of the long-chain, saturated fatty acids decreases with
increasing carbon number.
PMID- 11010931
TI - Prospective study of major dietary patterns and risk of coronary heart disease in
men.
AB - BACKGROUND: Previous studies on diet and coronary heart disease (CHD) focused
primarily on individual nutrients or foods. OBJECTIVE: We examined whether
overall dietary patterns derived from a food-frequency questionnaire (FFQ)
predict risk of CHD in men. DESIGN: This was a prospective cohort study of 44875
men aged 40-75 y without diagnosed cardiovascular disease or cancer at baseline
in 1986. RESULTS: During 8 y of follow-up, we documented 1089 cases of CHD
(nonfatal myocardial infarction and fatal CHD). Using factor analysis, we
identified 2 major dietary patterns using dietary data collected through a 131
item FFQ. The first factor, which we labeled the "prudent pattern," was
characterized by higher intake of vegetables, fruit, legumes, whole grains, fish,
and poultry, whereas the second factor, the "Western pattern," was characterized
by higher intake of red meat, processed meat, refined grains, sweets and dessert,
French fries, and high-fat dairy products. After adjustment for age and CHD risk
factors, the relative risks from the lowest to highest quintiles of the prudent
pattern score were 1.0, 0. 87, 0.79, 0.75, and 0.70 (95% CI: 0.56, 0.86; P: for
trend = 0.0009). In contrast, the relative risks across increasing quintiles of
the Western pattern score were 1.0, 1.21, 1.36, 1.40, and 1.64 (95% CI: 1.24,
2.17; P: for trend < 0.0001). These associations persisted in subgroup analyses
according to cigarette smoking, body mass index, and parental history of
myocardial infarction. CONCLUSIONS: These data suggest that major dietary
patterns derived from the FFQ predict risk of CHD, independent of other lifestyle
variables.
PMID- 11010932
TI - Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health
Study.
AB - BACKGROUND: Prospective data relating fruit and vegetable intake to
cardiovascular disease (CVD) risk are sparse, particularly for women. OBJECTIVE:
In a large, prospective cohort of women, we examined the hypothesis that higher
fruit and vegetable intake reduces CVD risk. DESIGN: In 1993 we assessed fruit
and vegetable intake among 39876 female health professionals with no previous
history of CVD or cancer by use of a detailed food-frequency questionnaire. We
subsequently followed these women for an average of 5 y for incidence of nonfatal
myocardial infarction (MI), stroke, percutaneous transluminal coronary
angioplasty, coronary artery bypass graft, or death due to CVD. RESULTS: During
195647 person-years of follow-up, we documented 418 incident cases of CVD
including 126 MIs. After adjustment for age, randomized treatment status, and
smoking, we observed a significant inverse association between fruit and
vegetable intake and CVD risk. For increasing quintiles of total fruit and
vegetable intake (median servings/d: 2. 6, 4.1, 5.5, 7.1, and 10.2), the
corresponding relative risks (RRs) were 1.0 (reference), 0.78, 0.72, 0.68, and
0.68 (95% CI comparing the 2 extreme quintiles: 0.51, 0.92; P: for trend = 0.01).
An inverse, though not statistically significant, trend remained after additional
adjustment for other known CVD risk factors, with RRs of 1.0, 0.75, 0.83, 0.80,
and 0.85 (95% CI for extreme quintiles: 0.61, 1.17). After excluding participants
with a self-reported history of diabetes, hypertension, or high cholesterol at
baseline, the multivariate-adjusted RR was 0.45 when extreme quintiles were
compared (95% CI: 0.22, 0.91; P: for trend = 0.09). Higher fruit and vegetable
intake was also associated with a lower risk of MI, with an adjusted RR of 0.62
for extreme quintiles (95% CI: 0.37, 1.04; P: for trend = 0.07). CONCLUSION:
These data suggest that higher intake of fruit and vegetables may be protective
against CVD and support current dietary guidelines to increase fruit and
vegetable intake.
PMID- 11010933
TI - Consumption of energy-dense, nutrient-poor foods by adult Americans: nutritional
and health implications. The third National Health and Nutrition Examination
Survey, 1988-1994.
AB - BACKGROUND: Current dietary guidance recommends limiting the intake of energy
dense, nutrient-poor (EDNP) foods, but little is known about recent consumption
patterns of these foods. OBJECTIVE: The contribution of EDNP foods to the
American diet and the associated nutritional and health implications were
examined. DESIGN: Data from the third National Health and Nutrition Examination
Survey (n = 15611; age >/=20 y) were used. EDNP categories included visible fats,
nutritive sweeteners and sweetened beverages, desserts, and snacks. The potential
independent associations of EDNP food intake with intakes of energy,
macronutrients, micronutrients, and serum vitamin, lipid, and carotenoid profiles
were examined with linear and logistic regression procedures. RESULTS: EDNP foods
supplied approximately 27% of energy intake; alcohol provided an additional 4%.
The relative odds of consuming foods from all 5 food groups and of meeting the
recommended dietary allowance or daily reference intake for protein and several
micronutrients decreased with increasing EDNP food intake (P: < 0.0001). Energy
intake and percentage of energy from fat were positively related to EDNP intake.
Serum concentrations of vitamins A, E, C, and B-12; folate; several carotenoids;
and HDL cholesterol were inversely related (P: = 0. 0005) whereas serum
homocysteine concentration was positively related (P: = 0.02) to EDNP food
intake. CONCLUSIONS: The results suggest that EDNP foods were consumed at the
expense of nutrient-dense foods, resulting in 1) increased risk of high energy
intake, 2) marginal micronutrient intake, 3) poor compliance with nutrient- and
food group-related dietary guidance, and 4) low serum concentrations of vitamins
and carotenoids.
PMID- 11010934
TI - Body composition and dietary intakes in adult celiac disease patients consuming a
strict gluten-free diet.
AB - BACKGROUND: Celiac disease responds to dietary gluten withdrawal, but data on the
long-term effects of gluten-free diets are discordant. OBJECTIVE: Our aim was to
evaluate the nutritional status and body composition of adult celiac disease
patients consuming a gluten-free diet who were in clinical, biochemical, and
histologic remission. DESIGN: We studied 71 patients (51 women and 20 men; mean
age: 27 y; range: 17-58 y) and 142 healthy control subjects matched by sex and
age. The subjects' height, weight, body mass index, fat and lean mass, and bone
mineral content (evaluated by dual-energy X-ray absorptiometry) were measured; a
3-d dietary questionnaire was administered; and total daily energy, fat,
carbohydrate, and protein intakes were calculated. RESULTS: The weight, height,
and body mass index of male celiac disease patients and the weight and body mass
index of female celiac disease patients were significantly lower than the
corresponding measurements in control subjects. The fat and lean mass of both
male and female patients was significantly different from that of control
subjects; however, bone mineral content was significantly lower only in females
in whom celiac disease was diagnosed in adulthood. Total energy intake was lower
in the patients than in the control subjects (9686 +/- 1569 and 11297 +/- 1318
kJ/d in males and 6736 +/- 1318 and 7740 +/- 1715 kJ/d in females), and the diet
of the patients was unbalanced, with a higher percentage of energy as fat and a
lower percentage of energy as carbohydrates. CONCLUSIONS: Although strictly
compliant with their gluten-free diet and in complete remission, patients with
celiac disease showed differences in body composition and dietary intakes
compared with control subjects. Strict follow-up and dietary advice in terms of
the choice and composition of foods seem necessary to prevent malnutrition.
PMID- 11010935
TI - Effects of enteral carbohydrates on de novo lipogenesis in critically ill
patients.
AB - BACKGROUND: Conversion of glucose into lipid (de novo lipogenesis; DNL) is a
possible fate of carbohydrate administered during nutritional support. It cannot
be detected by conventional methods such as indirect calorimetry if it does not
exceed lipid oxidation. OBJECTIVE: The objective was to evaluate the effects of
carbohydrate administered as part of continuous enteral nutrition in critically
ill patients. DESIGN: This was a prospective, open study including 25 patients
nonconsecutively admitted to a medicosurgical intensive care unit. Glucose
metabolism and hepatic DNL were measured in the fasting state or after 3 d of
continuous isoenergetic enteral feeding providing 28%, 53%, or 75% carbohydrate.
RESULTS: DNL increased with increasing carbohydrate intake (f1.gif" BORDER="0">
+/- SEM: 7.5 +/- 1.2% with 28% carbohydrate, 9.2 +/- 1.5% with 53% carbohydrate,
and 19.4 +/- 3.8% with 75% carbohydrate) and was nearly zero in a group of
patients who had fasted for an average of 28 h (1.0 +/- 0.2%). In multiple
regression analysis, DNL was correlated with carbohydrate intake, but not with
body weight or plasma insulin concentrations. Endogenous glucose production,
assessed with a dual-isotope technique, was not significantly different between
the 3 groups of patients (13.7-15.3 micromol * kg(-1) * min(-1)), indicating
impaired suppression by carbohydrate feeding. Gluconeogenesis was measured with
[(13)C]bicarbonate, and increased as the carbohydrate intake increased (from 2.1
+/- 0.5 micromol * kg(-1) * min(-1) with 28% carbohydrate intake to 3.7 +/- 0.3
micromol * kg(-1) * min(-1) with 75% carbohydrate intake, P: < 0. 05).
CONCLUSION: Carbohydrate feeding fails to suppress endogenous glucose production
and gluconeogenesis, but stimulates DNL in critically ill patients.
PMID- 11010936
TI - Energy metabolism after 2 y of energy restriction: the biosphere 2 experiment.
AB - BACKGROUND: An adaptive decrease in energy expenditure (EE) in response to 6 mo
of severely restricted energy intake was shown in a classic semistarvation study
the Minnesota experiment. OBJECTIVE: Our objective was to examine whether such
adaptation also occurs in response to less severe but sustained energy
restriction. DESIGN: Body composition, 1-wk total EE (TEE), 24-h sedentary EE,
and spontaneous physical activity were measured in 8 healthy subjects (4 men and
4 women) at the end of a 2-y confinement inside Biosphere 2. Unexpectedly, the
food supply was markedly restricted during most of the confinement and all
subjects experienced a marked, sustained weight loss (9.1 +/- 6.6 kg; P: < 0.001)
from the low-energy (7000-11000 kJ/d), low-fat (9% of energy), but nutrient
dense, diet they consumed. RESULTS: The TEE inside Biosphere 2, assessed 3 wk
before exit, averaged 10700 +/- 560 kJ/d (n = 8). Within 1 wk after exit, the
adjusted 24-h EE and spontaneous physical activity were lower in the biospherians
(n = 5) than in 152 control subjects (6% and 45%, respectively; both P: < 0.01).
Six months after exit and return to an ad libitum diet, body weight had increased
to preentry levels; however, adjusted 24-h EE and spontaneous physical activity
were still significantly lower than in control subjects. CONCLUSIONS: In lean
humans, an adaptive decrease in EE appears to occur not only in states of life
threatening undernutrition, but also in response to less severe energy
restriction sustained over several years.
PMID- 11010937
TI - Postprandial modulation of dietary and whole-body nitrogen utilization by
carbohydrates in humans.
AB - BACKGROUND: Sucrose exerts a sparing effect on whole-body protein metabolism,
mainly during the absorptive phase. OBJECTIVE: We aimed to characterize the acute
postprandial effect of addition of sucrose on deamination of dietary and
endogenous nitrogen, with particular consideration being given to the effects of
bioavailability. DESIGN: Twenty-one subjects equipped with ileal tubes ingested
(15)N-labeled soy protein combined with [(13)C]glycine, with (n = 10) or without
(n = 11) sucrose. Dietary and endogenous ileal flow of nitrogen were determined
from the ileal effluents. The kinetics of dietary amino acid transfer to the
blood were characterized by (13)CO(2) enrichment in breath and (15)N enrichment
in plasma amino acids. Deamination of dietary and endogenous amino acid was
determined from body urea, urinary nitrogen, and (15)N enrichment. RESULTS:
(13)CO(2) recovery in breath and (15)N plasma amino acid enrichments were highly
correlated (R:(2) >/= 0.95, P: < 0.001, for both meals) and markedly delayed by
sucrose (half-(13)CO(2) recovery: 274 min compared with 167 min), whereas
exogenous and endogenous ileal nitrogen kinetics and balances remained unchanged.
Addition of sucrose halved the early (0-2 h) deamination peak of dietary nitrogen
and reduced endogenous nitrogen oxidation over the first 4 h. Both were reduced
by 18-24% over the 8-h period after the meal. CONCLUSIONS: Without changing the
nitrogen absorptive balance, sucrose markedly affected the bioavailability
profile, which is governed by gastric emptying. Endogenous and dietary nitrogen
were not spared in the same way and over the same periods, showing that the
metabolism of endogenous and dietary nitrogen may be affected differently by
nutritional modulation, even if the effects are of a similar magnitude over the
entire postprandial period.
PMID- 11010938
TI - Iron deficiency anemia: higher prevalence in Mexican American than in non
Hispanic white females in the third National Health and Nutrition Examination
Survey, 1988-1994.
AB - BACKGROUND: Mexican American females have a higher prevalence of iron deficiency
than do non-Hispanic white females. OBJECTIVE: The objective was to estimate the
prevalence of iron deficiency anemia and examine potential reasons for this
difference between Mexican American (n = 1194) and non-Hispanic white (n = 1183)
females aged 12-39 y. DESIGN: We used data from the third National Health and
Nutrition Examination Survey (1988-1994). Iron deficiency anemia was defined as
abnormal results from >/=2 of 3 tests (erythrocyte protoporphyrin, transferrin
saturation, and serum ferritin) and a low hemoglobin concentration. We used
multiple logistic regression to adjust for factors that were more prevalent in
Mexican American females and significantly associated with iron deficiency
anemia. RESULTS: The prevalence of iron deficiency anemia was 6.2 +/- 0.8%
(f1.gif" BORDER="0"> +/- SE) in Mexican American females and 2.3 +/- 0.4% in non
Hispanic white females. Mean dietary iron intake, mean serum vitamin C
concentrations, and the proportion of females using oral contraceptives were
similar in the 2 groups. Age <20 y and education were not associated with iron
deficiency anemia. After adjustment for poverty level, parity, and iron
supplement use, the prevalence of iron deficiency anemia was 2.3 times higher in
Mexican American than in non-Hispanic white females (95% CI: 1.4, 3.9). In those
with a poverty income ratio (based on household income) >3.0, however, the
prevalence of iron deficiency anemia was 2.6 +/- 0.9% in Mexican American and 1.9
+/- 0.6% in non-Hispanic white females (NS). CONCLUSION: Although much of the
ethnic disparity in iron deficiency anemia remains unexplained, factors
associated with household income may be involved.
PMID- 11010939
TI - Use of vitamin-mineral supplements by female physicians in the United States.
AB - BACKGROUND: Rates of vitamin-mineral supplement use by US female physicians are
unknown but are of particular interest for several epidemiologic and clinical
reasons. OBJECTIVE: The objective was to determine rates of and variations in
vitamin-mineral supplement use among US female physicians. DESIGN: We used data
from the Women Physicians' Health Study, a large (n = 4501) national, randomly
sampled mail survey of female physicians aged 30-70 y. RESULTS: Half of the
physicians took a multivitamin-mineral supplement; 35.5% of these did so
regularly. However, =33% took any supplement other than calcium and <20% did so
regularly. Regular vitamin-mineral supplement use increased with age, and
antioxidant intake was higher in those at high risk of heart disease. Those with
a history of osteoporosis were nearly 3 times as likely as those with no history
to take supplemental calcium regularly. Those who took any supplement regularly
also consumed more fruit and vegetables daily than did occasional users or
nonusers (P: < 0.0001). Regular users of any supplement also consumed less fat
than did occasional users or nonusers (P: < 0.01). Additionally, vegetarians were
more likely than were nonvegetarians to regularly consume any supplement (59.9%
compared with 46.3%; P: < 0.001) and those who regularly consumed any supplement
were more likely to comply with US Preventive Services Task Force guidelines than
were those who were occasional users or nonusers (72.4% compared with 66.5% and
60.2%; P: < 0.0001). CONCLUSION: Female physicians, particularly those who were
especially health conscious or at higher risk of heart disease or osteoporosis,
used supplements at rates at least equal to those of women in the general
population.
PMID- 11010940
TI - Antioxidant and thyroid hormone status in selenium-deficient phenylketonuric and
hyperphenylalaninemic patients.
AB - BACKGROUND: Subjects consuming protein-restricted diets, such as patients with
phenylketonuria (PKU) or milder hyperphenylalaninemias (HPAs) are at risk of
selenium deficiency. Selenium is a cofactor of the antioxidant enzyme glutathione
peroxidase and of the thyroid hormone converting enzyme thyroxine deiodinase.
OBJECTIVE: Our goal was to investigate the effects of low plasma selenium on
antioxidant and thyroid hormone status. DESIGN: We assessed plasma selenium,
plasma total antioxidant status and the individual components thereof,
erythrocyte antioxidant status, and plasma thyroid hormones in 24 PKU and 10 HPA
patients and in 42 age-matched control subjects. RESULTS: Selenium was
significantly lower in both PKU and HPA patients than in control subjects and the
PKU patients had lower values than did the HPA patients. Total antioxidant status
was lower in both patient groups than in the control group, whereas alpha
tocopherol, albumin, and uric acid were not significantly different among groups.
Plasma selenium correlated well (r = 0.76) with erythrocyte glutathione
peroxidase. PKU patients had lower glutathione peroxidase activity than did HPA
patients and control subjects and lower glutathione concentrations than did
control subjects. Both patient groups had lower superoxide dismutase activity
than did control subjects. Free triiodothyronine was higher in both patient
groups than in control subjects, whereas free thyroxine was higher in the PKU
patients only. Free thyroxine and reverse triiodothyronine were inversely
correlated with selenium. CONCLUSION: Supplementation with selenium seems to be
advisable for patients consuming diets low in natural protein.
PMID- 11010941
TI - Adaptation in iron absorption: iron supplementation reduces nonheme-iron but not
heme-iron absorption from food.
AB - BACKGROUND: Results of cross-sectional studies suggest that in healthy people,
iron absorption adapts to meet physiologic needs and stabilize iron stores, but
this has not been adequately tested in longitudinal studies. OBJECTIVE: We tested
whether heme- and nonheme-iron absorption decrease in response to increased iron
intake and whether iron stores reach a steady state. DESIGN: In a randomized,
placebo-controlled trial, heme- and nonheme-iron absorption by healthy men and
women (n = 57) were measured before and after 12 wk of supplementation with 50 mg
Fe/d as ferrous sulfate. Serum and fecal ferritin were measured during
supplementation and for 6 mo thereafter. RESULTS: Initially, both heme- and
nonheme-iron absorption were inversely associated with serum ferritin
concentration. Volunteers who took iron supplements, even those with serum
ferritin <21 microg/L (n = 5), adapted to absorb less nonheme iron (3.2% at week
12 compared with 5.0% at week 0, P: < 0.001) but not less heme iron from a beef
based meal. Serum ferritin concentration was slightly but significantly higher
after iron supplementation than after placebo (difference = 13 microg/L). This
higher ferritin concentration persisted for >/=6 mo after supplementation, except
in subjects with low iron stores, whose serum ferritin returned to baseline
within 3 mo. Fecal ferritin excretion increased 2.5-fold (P: < 0.05) during
supplementation. CONCLUSIONS: Healthy individuals, even those with low iron
stores, had reduced nonheme-iron absorption from food in response to iron
supplementation. Despite this partial adaptation, iron stores were greater after
iron supplementation than after placebo and this difference was sustained, except
in individuals with the lowest iron stores.
PMID- 11010942
TI - Intake of specific carotenoids and risk of lung cancer in 2 prospective US
cohorts.
AB - BACKGROUND: Carotenoids may reduce lung carcinogenesis because of their
antioxidant properties; however, few studies have examined the relation between
intakes of individual carotenoids and lung cancer risk. OBJECTIVE: The aim of
this study was to examine the relation between lung cancer risk and intakes of
alpha-carotene, beta-carotene, lutein, lycopene, and beta-cryptoxanthin in 2
large cohorts. DESIGN: During a 10-y follow-up period, 275 new cases of lung
cancer were diagnosed in 46924 men; during a 12-y follow-up period, 519 new cases
were diagnosed in 77283 women. Carotenoid intakes were derived from the reported
consumption of fruit and vegetables on food-frequency questionnaires administered
at baseline and during follow-up. The data were analyzed separately for each
cohort and the results were pooled to compute overall relative risks (RRs).
RESULTS: In the pooled analyses, alpha-carotene and lycopene intakes were
significantly associated with a lower risk of lung cancer; the association with
beta-carotene, lutein, and beta-cryptoxanthin intakes were inverse but not
significant. Lung cancer risk was significantly lower in subjects who consumed a
diet high in a variety of carotenoids (RR: 0.68; 95% CI: 0.49, 0.94 for highest
compared with lowest total carotenoid score category). Inverse associations were
strongest after a 4-8-y lag between dietary assessment and date of diagnosis. In
subjects who never smoked, a 63% lower incidence of lung cancer was observed for
the top compared with the bottom quintile of alpha-carotene intake (RR: 0.37; 95%
CI: 0.18, 0.77). CONCLUSION: Data from 2 cohort studies suggest that several
carotenoids may reduce the risk of lung cancer.
PMID- 11010943
TI - Genomic DNA methylation decreases in response to moderate folate depletion in
elderly women.
AB - BACKGROUND: Methylation of genomic DNA is dependent on an adequate supply of
folate coenzymes. Previous data support the hypothesis that abnormal DNA
methylation plays an integral role in carcinogenesis. To date, no studies
assessing the effect of inadequate folate status on DNA methylation in older
women (aged >63 y) have been reported. OBJECTIVE: The effect of moderate folate
depletion followed by folate repletion on leukocyte genomic DNA methylation was
investigated in elderly women (aged 60-85 y) to evaluate whether DNA methylation
could be used as a functional indicator of folate status. DESIGN: Healthy,
postmenopausal women (n = 33) consumed a moderately folate-depleted diet (118
microg folate/d) for 7 wk, followed by 7 wk of folate repletion with 200 or 415
microg/d, each provided as 2 different dietary treatments for a total of 4
treatment groups (n = 30). Leukocyte DNA methylation was determined on the basis
of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:
adenosylmethionine in an in vitro assay. RESULTS: Incorporation of [(3)H]methyl
groups increased significantly (P: = 0.0025) in response to folate depletion,
suggesting undermethylation of DNA. No significant changes were detected in
[(3)H]methyl incorporation in any group over the 7-wk repletion period compared
with postdepletion values. CONCLUSIONS: DNA methylation status may be used as a
functional indicator of moderately depleted folate status. The slow response to
the repletion diets observed suggests that normalization of DNA methylation after
moderate folate depletion may be delayed in older women.
PMID- 11010944
TI - Responsiveness of dark-adaptation threshold to vitamin A and beta-carotene
supplementation in pregnant and lactating women in Nepal.
AB - BACKGROUND: Impaired dark adaptation occurs commonly in vitamin A deficiency.
OBJECTIVE: We sought to examine the responsiveness of dark-adaptation threshold
to vitamin A and beta-carotene supplementation in Nepali women. DESIGN: The dark
adapted pupillary response was tested in 298 pregnant women aged 15-45 y in a
placebo-controlled trial of vitamin A and beta-carotene; 131 of these women were
also tested at 3 mo postpartum. Results were compared with those for 100
nonpregnant US women of similar age. The amount of light required for pupillary
constriction was recorded after bleaching and dark adaptation. RESULTS: Pregnant
women receiving vitamin A had better dark-adaptation thresholds (-1.24 log
cd/m(2)) than did those receiving placebo (-1.11 log cd/m(2); P: = 0. 03) or beta
carotene (-1.13 log cd/m(2); P: = 0.05) (t tests with Bonferroni correction).
Dark-adaptation threshold was associated with serum retinol concentration in
pregnant women receiving placebo (P: = 0.001) and in those receiving beta
carotene (P: = 0.003) but not in those receiving vitamin A. Among women receiving
placebo, mean dark-adaptation thresholds were better during the first trimester (
1.23 log cd/m(2)) than during the second and third trimesters (-1.03 log cd/m(2);
P: = 0.02, t test). The mean threshold of nonpregnant US women (-1.35 log
cd/m(2)) was better than that of all 3 Nepali groups (P: < 0.001, t test, for all
3 groups). CONCLUSIONS: During pregnancy, pupillary dark adaptation was strongly
associated with serum retinol concentration and improved significantly in
response to vitamin A supplementation. This noninvasive testing technique is a
valid indicator of population vitamin A status in women of reproductive age.
PMID- 11010945
TI - Infant growth patterns in the slums of Dhaka in relation to birth weight,
intrauterine growth retardation, and prematurity.
AB - BACKGROUND: Relations between size and maturity at birth and infant growth have
been studied inadequately in Bangladesh, where the incidence of low birth weight
is high and most infants are breast-fed. OBJECTIVE: This study was conducted to
describe infant growth patterns and their relations to birth weight, intrauterine
growth retardation, and prematurity. DESIGN: A total of 1654 infants born in
selected low-socioeconomic areas of Dhaka, Bangladesh, were enrolled at birth.
Weight and length were measured at birth and at 1, 3, 6, 9, and 12 mo of age.
RESULTS: The infants' mean birth weight was 2516 g, with 46.4% weighing <2500 g;
70% were small for gestational age (SGA) and 17% were premature. Among the SGA
infants, 63% had adequate ponderal indexes. The mean weight of the study infants
closely tracked the -2 SD curve of the World Health Organization pooled breast
fed sample. Weight differences by birth weight, SGA, or preterm categories were
retained throughout infancy. Mean z scores based on the pooled breast-fed sample
were -2.38, -1. 72, and -2.34 at birth, 3 mo, and 12 mo. Correlation analysis
showed greater plasticity of growth in the first 3 mo of life than later in the
first year. CONCLUSIONS: Infant growth rates were similar to those observed among
breast-fed infants in developed countries. Most study infants experienced chronic
intrauterine undernourishment. Catch-up growth was limited and weight at 12 mo
was largely a function of weight at birth. Improvement of birth weight is likely
to lead to significant gains in infant nutritional status in this population,
although interventions in the first 3 mo are also likely to be beneficial.
PMID- 11010946
TI - Tracking of body mass index from childhood to adolescence: a 6-y follow-up study
in China.
AB - BACKGROUND: Although extensive descriptive research shows that childhood obesity
predisposes a person to adult obesity, little is understood about the dynamics of
weight during childhood and the predictors of weight tracking. OBJECTIVE: Our
objective was to examine tracking patterns of body mass index (BMI) as well as
their predictors between childhood and adolescence. DESIGN: A cohort of 975
Chinese children aged 6-13 y was followed for 6 y (1991-1997). Tracking of BMI
was defined as an individual maintaining a certain status (overweight or
underweight) or relative position (relative BMI quartile) over time. Relative BMI
related BMI to age- and sex-specific BMI cutoffs. RESULTS: After 6 y,
approximately 40% of the subjects had maintained their relative positions, but
30% had moved into a lower or higher quartile. The BMIs of thin and fat children
were more likely to track: 51% and 46% remained in the bottom and upper
quartiles, respectively. Nearly one-third of the underweight children remained
underweight in 1997. Overweight children were 2.8 times as likely as all other
children to become overweight adolescents; underweight children were 3.6 times as
likely to remain underweight as adolescents. Parental obesity and underweight,
individuals' initial BMIs, dietary fat intake, and family income helped predict
tracking and changes in BMI. CONCLUSION: In a society undergoing enormous changes
in diet and activity, BMI tracking is still very important between childhood and
adolescence in China.
PMID- 11010947
TI - Energy expenditure of stunted and nonstunted boys and girls living in the
shantytowns of Sao Paulo, Brazil.
AB - BACKGROUND: Stunting increases the risk of obesity in developing countries,
particularly in girls and women, but the underlying reason is not known.
OBJECTIVE: Our objective was to test the hypothesis that stunted children have
lower energy expenditure than do nonstunted children, a factor that has predicted
an increased risk of obesity in other high-risk populations. DESIGN: A cross
sectional study was conducted in shantytown children from Sao Paulo, Brazil.
Twenty-eight stunted children aged 8-11 y were compared with 30 nonstunted
children with similar weight-for-height. Free-living total energy expenditure
(TEE) was measured over 7 d by using the doubly labeled water method. In
addition, resting energy expenditure (REE) was measured by indirect calorimetry
and body composition was measured by dual-energy X-ray absorptiometry. RESULTS:
There were no significant associations between stunting and any measured energy
expenditure parameter, including REE adjusted for weight (f1.gif" BORDER="0"> +/-
SEM: 4575 +/- 95 compared with 4742 +/- 91 kJ/d, in stunted and nonstunted
children, respectively) and TEE adjusted for weight (8424 +/- 239 compared with
8009 +/- 221 kJ/d, in stunted and nonstunted children, respectively). In multiple
regression models that included fat-free mass and fat mass, girls had
significantly lower TEE than did boys (P: < 0.05) but not significantly lower REE
(P: = 0.17). CONCLUSIONS: There was no association between stunting and energy
expenditure after differences between groups in body size and composition were
accounted for. However, the girls had lower TEE than did boys, which may help to
explain the particularly high risk of obesity in stunted adolescent girls and
women in urban areas of developing countries.
PMID- 11010948
TI - Prevalence and trends of overweight among preschool children in developing
countries.
AB - BACKGROUND: Obesity during childhood is a matter of growing concern. Several
reports show increasing rates of obesity in developed countries, whereas the
extent of the problem in developing countries remains unknown. OBJECTIVE: The aim
of this study was to fill this gap by quantifying the prevalence and trends of
overweight among preschool children in developing countries. DESIGN: One hundred
sixty nationally representative cross-sectional surveys from 94 countries were
analyzed in a standardized way to allow comparisons across countries and over
time. Overweight was defined as a weight-for-height >2 SDs from the National
Center for Health Statistics/World Health Organization international reference
median. Prevalences of wasted children (< -2 SDs) are also presented to enable
comparisons between both ends of the distribution. RESULTS: The global prevalence
of overweight was 3.3%. Some countries and regions, however, had considerably
higher rates, and overweight was shown to increase in 16 of 38 countries with
trend data. Countries with the highest prevalences of overweight are located
mainly in the Middle East, North Africa, and Latin America. Rates of wasting were
generally higher than those of overweight; Africa and Asia had wasting rates 2.5
3.5 times higher than overweight rates. Countries with high wasting rates tended
to have low overweight rates and vice versa. CONCLUSIONS: These estimates show
that attention should be paid to monitoring levels and trends of overweight in
children. This, however, should not be done at the expense of decreasing
international commitments to alleviating undernutrition. The data presented
confirm that undernutrition remains a major public health problem worldwide.
PMID- 11010949
TI - How do fiber-supplemented formulas affect antroduodenal motility during enteral
nutrition? A comparative study between mixed and insoluble fibers.
AB - BACKGROUND: Fiber supplementation during enteral nutrition has been recommended,
but the effect of soluble compared with insoluble fiber supplements on
antroduodenal motility is unknown. OBJECTIVE: The objective of this study was to
compare antroduodenal motor patterns in 8 healthy volunteers during and after
gastric infusion of 3 different diets: a fiber-free diet, an insoluble-fiber
diet, and a mixed-fiber diet (50% soluble fiber and 50% insoluble fiber). DESIGN:
Manometric studies with the 3 different diets (2100 kJ) were performed in random
order. Antroduodenal motility was monitored continuously for 6 h by using a
pneumohydraulic system to calculate the number, amplitude, and duration of the
pressure waves; the area under the curve (AUC); and the percentage of time
occupied by motor activity before, during, and after each type of infusion.
Variations in antral areas were measured by ultrasonography. RESULTS: The gastric
motor response was significantly higher, whatever the diet, in the distal antral
recording site than in the 2 more proximal sites. In the proximal but not the
distal antrum, the number of waves, the AUC, and the percentage of time occupied
by motor activity were higher (P: < 0.04) with the mixed-fiber than with the
insoluble-fiber diet. No significant differences in variations of antral area
were observed among the 3 diets. In the duodenum, motor variables were not
significantly different among the 3 diets. CONCLUSIONS: A gastric infusion
induced a greater motor response in the distal than in the proximal antrum. A
mixed-fiber diet was associated with significantly greater proximal antral
motility than was an insoluble-fiber diet. There was no significant difference
among the 3 formulas in duodenal motor variables or in variations in antral area
as measured by ultrasound.
PMID- 11010950
TI - Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach
cancers.
AB - BACKGROUND: Animal and in vitro studies have provided evidence of an
anticarcinogenic effect of active ingredients in garlic. OBJECTIVE: The objective
was to conduct meta-analyses of the epidemiologic literature on the association
between garlic consumption and risk of stomach, colon, head and neck, lung,
breast, and prostate cancers. DESIGN: Meta-analyses were conducted for all
cancers mutually and separately for colorectal and stomach cancers in relation to
consumption of exclusively raw garlic, cooked garlic, or both (RC garlic).
Eighteen studies reported a relative risk estimate for RC garlic consumption and
cancer risk. RESULTS: In the meta-analyses of colorectal and stomach cancer, the
reference categories ranged from no consumption to consumption of 3.5 g/wk,
whereas the highest categories ranged from any consumption to >28.8 g/wk. The
average difference between the highest and lowest categories was 16 g/wk. The
random-effects relative risk (RR) estimate of colorectal cancer and RC garlic
consumption, excluding garlic supplements, was 0.69 (95% CI: 0.55, 0.89). For
stomach cancer, the random-effects RR estimate was 0.53 (95% CI: 0.31, 0.92). The
heterogeneity among studies for the latter outcome (P: = 0.0002) indicates the
questionableness of the generalizability of this summary estimate. An indication
of publication bias for all cancers combined is evident from a funnel plot of RC
garlic consumption and cancer risk and from the results of the Begg and Mazumdar
test (P: = 0.049). CONCLUSIONS: High intake of RC garlic may be associated with a
protective effect against stomach and colorectal cancers. Heterogeneity of effect
estimates, differences in dose estimation, publication bias, and possible
alternative hypotheses (eg, confounding by total vegetable consumption) preclude
sole reliance on summary effect estimates.
PMID- 11010951
TI - Comparison of total body potassium with other techniques for measuring lean body
mass in men and women with AIDS wasting.
AB - BACKGROUND: Lean body mass is an important predictor of survival and functional
status in patients with AIDS wasting. The bias between different techniques for
assessing body composition in AIDS wasting is not known. DESIGN: We compared
total body potassium (TBK) with fat-free mass (FFM) determined by dual-energy X
ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and skinfold
thickness measurement (SKF) in 132 patients (63 men, 69 women) with AIDS wasting
(weight < 90% of ideal body weight, or weight loss > 10% of original, or both).
None of the subjects exhibited clinical lipodystrophy. Comparisons were made by
using different BIA equations. RESULTS: Lean body mass determined by DXA was
highly correlated with TBK in men (r = 0.79, P: < 0.0001) and women (r = 0.84, P:
< 0.0001). FFM(BIA) and FFM(DXA) were significantly different (P: < 0.01 in men
and P: < 0.0001 in women). The difference between FFM(DXA) and FFM(BIA) was
significantly greater with greater weight and body fat, particularly in HIV
infected women (r = -0.39, P: = 0.001 for weight; r = -0.60, P: < 0.0001 for
fat). The comparability of FFM and fat mass determined by DXA and BIA was
dependent on the specific BIA equation used. Among men, no single BIA equation
was more highly predictive of fat mass and FFM in comparison with DXA.
CONCLUSIONS: The differences between DXA, BIA, and SKF in the determination of
fat mass and FFM are significant in patients with AIDS wasting. BIA overestimates
FFM compared with DXA in those with greater body fat. Standard BIA equations may
not accurately estimate FFM and fat mass in men and women with AIDS wasting.
PMID- 11010953
TI - No evidence for a link between consumption of chocolate and coronary heart
disease.
PMID- 11010956
TI - High-carbohydrate diets, physical activity, and plasma lipoprotein lipids.
PMID- 11010957
TI - Breast-feeding, breast-milk feeding, and intelligence quotient.
PMID- 11010958
TI - Physiologically meaningful biological models.
PMID- 11010959
TI - Widespread distribution of binding sites for the novel Ca2+-mobilizing messenger,
nicotinic acid adenine dinucleotide phosphate, in the brain.
AB - Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca(2+)
mobilizing agent in invertebrate eggs that has recently been shown to be active
in certain mammalian and plant systems. Little, however, is known concerning the
properties of putative NAADP receptors. Here, for the first time, we report
binding sites for NAADP in brain. In contrast to sea urchin egg homogenates,
[(32)P]NAADP bound reversibly to multiple sites in brain membranes. The rank
order of potency of NAADP, 2',3'-cyclic NAADP and 3'-NAADP in displacing
[(32)P]NAADP was, however, the same in the two systems and in agreement with
their ability to mobilize Ca(2+) from homogenates. These data indicate that
[(32)P]NAADP likely binds to receptors mediating Ca(2+) mobilization.
Autoradiography revealed striking heterogeneity in the distribution of
[(32)P]NAADP binding sites throughout the brain. Our data strongly support a role
for NAADP-induced Ca(2+) signaling in the brain.
PMID- 11010961
TI - Involvement of phospholipid hydroperoxide glutathione peroxidase in the
modulation of prostaglandin D2 synthesis.
AB - Antigenic cross-linking of the high affinity IgE receptors on mast cells induced
the synthesis of prostaglandin D(2) (PGD(2)). The production of PGD(2) in L9
cells, which overexpressed non-mitochondrial phospholipid glutathione peroxidase
(PHGPx), was only one-third that in the control line of cells (S1 cells). The
reduction in the formation of PGD(2) in L9 cells was reversed upon inhibition of
PHGPx activity by buthionine sulfoximine. Experiments with inhibitors
demonstrated that prostaglandin H synthase-2 (PGHS-2) was the isozyme responsible
for the production of PGD(2) upon cross-linking of IgE receptors. The conversion
of radiolabeled arachidonic acid to prostaglandin H(2) (PGH(2)) was strongly
inhibited in L9 cells, whereas the rate of conversion of PGH(2) to PGD(2) was the
same in L9 cells and S1 cells, indicating that PGHS was inactivated in L9 cells.
The PGHS activity in L9 cells was about half that in S1 cells. However, PGHS
activity in L9 cells increased to the level in S1 cells upon the addition of the
hydroperoxide 15-hydroperoxyeicosatetraenoic acid or of 3-chloroperoxybenzoic
acid. These results suggest that non-mitochondrial PHGPx might be involved in the
inactivation of PGHS-2 in nucleus and endoplasmic reticulum via reductions in
levels of the hydroperoxides that are required for full activation of PGHS.
Therefore, it appears that PHGPx might function as a modulator of the production
of prostanoids, in addition to its role as an antioxidant enzyme.
PMID- 11010960
TI - Identification of a novel neuromedin U receptor subtype expressed in the central
nervous system.
AB - Neuromedin U is a neuropeptide prominently expressed in the upper
gastrointestinal tract and central nervous system. Recently, GPR66/FM-3 (NmU-R1)
was identified as a specific receptor for neuromedin U. A BLAST search of the
GenBank(TM) genomic database using the NmU-R1 cDNA sequence revealed a human
genomic fragment encoding a G protein-coupled receptor that we designated NmU-R2
based on its homology to NmU-R1. The full-length NmU-R2 cDNA was subsequently
cloned, stably expressed in 293 cells, and shown to mobilize intracellular
calcium in response to neuromedin U. This response was dose-dependent (EC(50) = 5
nm) and specific in that other neuromedins did not induce a calcium flux in
receptor-transfected cells. Expression analysis of human NmU-R2 demonstrated its
mRNA to be most highly expressed in central nervous system tissues. Based on
these data, we conclude that NmU-R2 is a novel neuromedin U receptor subtype that
is likely to mediate central nervous system-specific neuromedin U effects.
PMID- 11010962
TI - Interaction between the unphosphorylated receptor with high affinity for IgE and
Lyn kinase.
AB - Chinese hamster ovary fibroblasts previously transfected with the high affinity
receptor for IgE (FcepsilonRI) were further transfected with the alpha subunit of
the receptor for interleukin 2 (Tac) or with chimeric constructs in which the
cytoplasmic domain of Tac was replaced with the C-terminal cytoplasmic domain of
either the beta subunit or the gamma subunit of FcepsilonRI. Whereas native Tac
failed to affect the aggregation-induced phosphorylation of FcepsilonRI, both
chimeric constructs substantially inhibited this reaction. Alternatively, the
FcepsilonRI-bearing fibroblasts were transfected with two chimeric constructs in
which the cytoplasmic domain of Tac was replaced with a modified short form of
Lyn kinase. The Lyn in both of the chimeric constructs had been mutated to remove
the sites that are normally myristoylated and palmitoylated, respectively; one of
the constructs had in addition been altered to be catalytically inactive. The
catalytically active construct enhanced, and the inactive construct inhibited,
aggregation-induced phosphorylation of the receptors. All of the chimeric
constructs were largely distributed outside the detergent resistant microdomains,
and whereas aggregation caused them to move to the domains in part, their
aggregation was neither necessary nor enhanced their effects. These results and
others indicate that the receptor and Lyn interact through protein-protein
interactions that neither are dependent upon either the post-translational
modification of the kinase with lipid moieties nor result exclusively from their
co-localization in specialized membrane domains.
PMID- 11010963
TI - Regulation of the ligand binding activity of the human very low density
lipoprotein receptor by protein kinase C-dependent phosphorylation.
AB - The very low density lipoprotein receptor (VLDL-R) binds and internalizes several
ligands, including very low density lipoprotein (VLDL), urokinase-type
plasminogen activator:plasminogen activator inhibitor type 1 complexes,
lipoprotein lipase, and the 39-kDa receptor-associated protein that copurifies
with the low density lipoprotein receptor-related protein/alpha(2)-macroglobulin
receptor. Although several agonists regulate VLDL-R mRNA and/or protein
expression, post-transcriptional regulation of receptor activity has not been
described. Here, we report that the ligand binding activity of the VLDL-R in THP
1 monocytic cells, endothelial cells, smooth muscle cells, and VLDL-R-transfected
HEK 293 cells is diminished after treatment with phorbol 12-myristate 13-acetate.
This response was blocked by inhibitors of protein kinase C (PK-C), including a
specific inhibitor of the PK-C beta II isoform, and was associated with
phosphorylation of serine residues in the cytoplasmic domain of the receptor.
Culture of endothelial cells in the presence of high glucose concentrations,
which stimulate diacylglycerol synthesis and PK-C beta II activation, also
induced a PK-C-dependent loss of VLDL-R ligand binding activity. Taken together,
these studies demonstrate that the ligand binding activity of the VLDL-R is
regulated by PK-C-dependent phosphorylation and that hyperglycemia may diminish
VLDL-R activity.
PMID- 11010964
TI - Molecular and functional characterization of organic cation/carnitine transporter
family in mice.
AB - Carnitine is essential for beta-oxidation of fatty acids, and a defect of cell
membrane transport of carnitine leads to fatal systemic carnitine deficiency. We
have already shown that a defect of the organic cation/carnitine transporter
OCTN2 is a primary cause of systemic carnitine deficiency. In the present study,
we further isolated and characterized new members of the OCTN family, OCTN1 and
3, in mice. All three members were expressed commonly in kidney, and OCTN1 and -2
were also expressed in various tissues, whereas OCTN3 was characterized by
predominant expression in testis. When their cDNAs were transfected into HEK293
cells, the cells exhibited transport activity for carnitine and/or the organic
cation tetraethylammonium (TEA). Carnitine transport by OCTN1 and OCTN2 was Na(+)
dependent, whereas that by OCTN3 was Na(+)-independent. TEA was transported by
OCTN1 and OCTN2 but not by OCTN3. The relative uptake activity ratios of
carnitine to TEA were 1.78, 11.3, and 746 for OCTN1, -2, and -3, respectively,
suggesting high specificity of OCTN3 for carnitine and significantly lower
carnitine transport activity of OCTN1. Thus, OCTN3 is unique in its limited
tissue distribution and Na(+)-independent carnitine transport, whereas OCTN1
efficiently transported TEA with minimal expression of carnitine transport
activity and may have a different role from other members of the OCTN family.
PMID- 11010965
TI - Selective degradation of oxidized calmodulin by the 20 S proteasome.
AB - We have investigated the mechanisms that target oxidized calmodulin for
degradation by the proteasome. After methionine oxidation within calmodulin,
rates of degradation by the 20 S proteasome are substantially enhanced. Mass
spectrometry was used to identify the time course of the proteolytic fragments
released from the proteasome. Oxidized calmodulin is initially degraded into
large proteolytic fragments that are released from the proteasome and
subsequently degraded into small peptides that vary in size from 6 to 12 amino
acids. To investigate the molecular determinants that result in the selective
degradation of oxidized calmodulin, we used circular dichroism and fluorescence
spectroscopy to assess oxidant-induced structural changes. There is a linear
correlation between decreases in secondary structure and the rate of degradation.
Calcium binding or the repair of oxidized calmodulin by methionine sulfoxide
reductase induces comparable changes in alpha-helical content and rates of
degradation. In contrast, alterations in the surface hydrophobicity of oxidized
calmodulin do not alter the rate of degradation by the proteasome, indicating
that changes in surface hydrophobicity do not necessarily lead to enhanced
proteolytic susceptibility. These results suggest that decreases in secondary
structure expose proteolytically sensitive sites in oxidized calmodulin that are
cleaved by the proteasome in a nonprocessive manner.
PMID- 11010966
TI - Molecular cloning of the human kallikrein 15 gene (KLK15). Up-regulation in
prostate cancer.
AB - Kallikreins are a subgroup of serine proteases with diverse physiological
functions. Growing evidence suggests that many kallikreins are implicated in
carcinogenesis. By using molecular cloning techniques, we identified a new human
kallikrein gene, tentatively named KLK15 (for kallikrein 15 gene). This new gene
maps to chromosome 19q13.4 and is located between the KLK1 and KLK3 genes. KLK15
is formed of five coding exons and four introns, and shows structural similarity
to other kallikreins and kallikrein-like genes. KLK15 has three alternatively
spliced forms and is primarily expressed in the thyroid gland and to a lower
extent in the prostate, salivary, and adrenal glands and in the colon testis and
kidney. Our preliminary results indicate that the expression of KLK15 is up
regulated by steroid hormones in the LNCaP prostate cancer cell line. The KLK15
gene is also up-regulated, at the mRNA level, in prostate cancer in comparison to
normal prostatic tissue. KLK15 up-regulation was found to be associated with more
aggressive forms of prostate cancer. This newly discovered gene has the potential
of being used as a diagnostic and/or prognostic marker for prostate cancer.
PMID- 11010967
TI - Synergistic, p160 coactivator-dependent enhancement of estrogen receptor function
by CARM1 and p300.
AB - Members of the p160 coactivator family (steroid receptor coactivator-1 (SRC-1),
glucocorticoid receptor interacting protein 1 (GRIP1), and activator of thyroid
and retinoic acid receptors (ACTR)) mediate transcriptional activation by nuclear
receptors. After being recruited to the promoter by nuclear receptors, the p160
coactivator transmits the activating signal via two C-terminal activation
domains, AD1 and AD2. AD1 is a binding site for the related coactivators cAMP
response element binding protein binding protein (CBP) and p300, whereas AD2
binds to another coactivator, coactivator-associated arginine methyltransferase 1
(CARM1), a protein-arginine methyltransferase. The current study explored the
cooperative functional and mechanistic relationships among GRIP1, CARM1, and p300
in transient transfection assays, where they enhanced the ability of the estrogen
receptor (ER) to activate transcription of a reporter gene. The coactivator
functions of p300 and CARM1 depended on the co-expression of GRIP1. Simultaneous
co-expression of all three coactivators caused a synergistic enhancement of ER
function. Deletion of the AD1 domain of GRIP1 abolished the ability of p300 to
potentiate ER activity but had no effect on CARM1-mediated stimulation. In
contrast, when the AD2 domain of GRIP1 was deleted, p300 still stimulated ER
function through the mutant GRIP1, but CARM1 failed to do so. Thus, both binding
of p300 to AD1 and binding of CARM1 to AD2 are required for their respective
coactivator functions and for their synergy. Furthermore, CARM1 and p300 function
independently through different activating domains of GRIP1, and their synergy
suggests that they enhance transcription by different, complementary mechanisms.
PMID- 11010968
TI - Identification and characterization of a novel follistatin-like protein as a
binding protein for the TGF-beta family.
AB - Follistatin is an activin-binding protein that prevents activin from binding to
its receptors and neutralizes its activity. Follistatin also binds bone
morphogenetic proteins (BMPs). In this study, we report the identification of a
novel follistatin-like protein from mouse. The mouse cDNA encodes a 256-residue
precursor and most likely a mouse homologue of human FLRG, which was found at the
breakpoint of the chromosomal rearrangement in a B-cell line. Whereas follistatin
has three follistatin domains, which are presumed to be growth factor binding
motifs, FLRG possesses only two follistatin domains. Northern blotting revealed
that mRNAs for FLRG were abundantly expressed in heart, lung, kidney, and testis
in mouse. The recombinant mouse FLRG proteins were found to have binding activity
for both activin and bone morphogenetic protein-2. Like follistatin, FLRG has
higher affinity for activin than for BMP-2. The FLRG protein inhibited activin
induced and BMP-2-induced transcriptional responses in a dose-dependent manner.
Glutathione S-transferase fusion proteins encoding various regions of FLRG were
produced and studied. Ligand blotting using (125)I-activin revealed that the COOH
terminal region containing the second follistatin domain was able to bind
activin. Our finding implies that cellular signaling by activin and BMPs is
tightly regulated by multiple members of the follistatin family.
PMID- 11010969
TI - The isolation, characterization, and molecular cloning of a 75-kDa gelatinase B
like enzyme, a member of the matrix metalloproteinase (MMP) family. An avian
enzyme that is MMP-9-like in its cell expression pattern but diverges from
mammalian gelatinase B in sequence and biochemical properties.
AB - We have isolated a novel 75-kDa gelatinase from a chicken macrophage cell line,
HD11. Biochemical and immunological characterization of the purified enzyme
demonstrated that it is distinct from the chicken 72-kDa gelatinase A (MMP-2).
The enzyme is capable of specific gelatin binding and rapid gelatin cleavage.
Incubation with an organomercurial compound (p-aminophenylmercuric acetate)
induces proteolytic processing and activation of this enzyme, and the resultant
gelatinolytic activity is sensitive to both zinc chelators and tissue inhibitors
of metalloproteinases. A full-length cDNA for the enzyme has been cloned, and
sequence analysis demonstrated that the enzyme possesses the characteristic
multidomain structure of an MMP gelatinase including a cysteine switch prodomain,
three fibronectin type II repeats, a catalytic zinc binding region, and a
hemopexin-like domain. The 75-kDa gelatinase is produced by phorbol ester-treated
chicken bone marrow cells, monocytes, and polymorphonuclear leukocytes, cell
types that charac- teristically produce the 92-kDa mammalian gelatinase B (MMP
9). The absence of a 90-110-kDa gelatinase in these cell types indicates that the
75-kDa gelatinase is likely the avian counterpart of gelatinase B. However, the
protein is only 59% identical to human gelatinase B, whereas all previously
cloned chicken MMP homologues are 75-90% identical to their human counterparts.
In addition, the new 75-kDa chicken gelatinase lacks the type V collagen domain
that is found in all mammalian gelatinase Bs. Furthermore, the secreted enzyme
appears structurally distinct from known gelatinase Bs and the activated enzyme
can cleave fibronectin, which is not a substrate for mammalian gelatinase B. Thus
the results of this study indicate that a second MMP gelatinase exists in
chickens, and although it is MMP-9/gelatinase B-like in its overall domain
structure and expression pattern, it appears to be biochemically divergent from
mammalian gelatinase B.
PMID- 11010970
TI - Regulation of a Ca2+-sensitive adenylyl cyclase in an excitable cell. Role of
voltage-gated versus capacitative Ca2+ entry.
AB - In nonexcitable cells, we had previously established that Ca(2+)-sensitive
adenylyl cyclases, whether expressed endogenously or heterologously, were
regulated exclusively by capacitative Ca(2+) entry (Fagan, K. A., Mahey, R. and
Cooper, D. M. F. (1996) J. Biol. Chem. 271, 12438-12444; Fagan, K. A., Mons, N.,
and Cooper, D. M. F. (1998) J. Biol. Chem. 273, 9297-9305). Relatively little is
known about how these enzymes are regulated by Ca(2+) in excitable cells, where
they predominate. Furthermore, no effort has been made to determine whether the
prominent voltage-gated Ca(2+) entry, which typifies excitable cells, overwhelms
the effect of any capacitative Ca(2+) entry that may occur. In the present study,
we placed the Ca(2+)-stimulable, adenylyl cyclase type VIII in an adenovirus
vector to optimize its expression in the pituitary-derived GH(4)C(1) cell line.
In these cells, a modest degree of capacitative Ca(2+) entry could be discerned
in the face of a dramatic voltage-gated Ca(2+) entry. Nevertheless, both modes of
Ca(2+) entry were equally efficacious at stimulating adenylyl cyclase. A striking
release of Ca(2+) from intracellular stores, triggered either by ionophore or
thyrotrophin-releasing hormone, was incapable of stimulating the adenylyl
cyclase. It thus appears as though the intimate colocalization of adenylyl
cyclase with capacitative Ca(2+) entry channels is an intrinsic property of these
molecules, regardless of whether they are expressed in excitable or nonexcitable
cells.
PMID- 11010971
TI - Alternative splicing in intracellular loop connecting domains II and III of the
alpha 1 subunit of Cav1.2 Ca2+ channels predicts two-domain polypeptides with
unique C-terminal tails.
AB - Novel splice variants of the alpha(1) subunit of the Ca(v)1.2 voltage-gated
Ca(2+) channel were identified that predicted two truncated forms of the alpha(1)
subunit comprising domains I and II generated by alternative splicing in the
intracellular loop region linking domains II and III. In rabbit heart splice
variant 1 (RH-1), exon 19 was deleted, which resulted in a reading frameshift of
exon 20 with a premature termination codon and a novel 19-amino acid carboxyl
terminal tail. In the RH-2 variant, exons 17 and 18 were deleted, leading to a
reading frameshift of exons 19 and 20 with a premature stop codon and a novel 62
amino acid carboxyl-terminal tail. RNase protection assays with RH-1 and RH-2
cRNA probes confirmed the expression in cardiac and neuronal tissue but not
skeletal muscle. The deduced amino acid sequence from full-length cDNAs encoding
the two variants predicted polypeptides of 99.0 and 99.2 kDa, which constituted
domains I and II of the alpha(1) subunit of the Ca(v)1.2 channel. Antipeptide
antibodies directed to sequences in the second intracellular loop between domains
II and III identified the 240-kDa Ca(v)1.2 subunit in sarcolemmal and heavy
sarcoplasmic reticulum (HSR) membranes and a 99-kDa polypeptide in the HSR. An
antipeptide antibody raised against unique sequences in the RH-2 variant also
identified a 99-kDa polypeptide in the HSR. These data reveal the expression of
additional Ca(2+) channel structural units generated by alternative splicing of
the Ca(v)1.2 gene.
PMID- 11010973
TI - CHOP/GADD153 gene expression response to cellular stresses inhibited by prior
exposure to ultraviolet light wavelength band C (UVC). Inhibitory sequence
mediating the UVC response localized to exon 1.
AB - CHOP/GADD153 is both an activating and repressing transcription factor that is
markedly induced in response to a variety of cellular stresses. The CHOP/GADD153
gene was originally cloned because of its inducibility by ultraviolet light
wavelength band C (UVC) and has since been found to be activated in response to
many different cellular stresses. Some of the recent studies have questioned the
UVC responsiveness of the CHOP gene. Contradiction in our own data led us to
reexamine the UVC effects on CHOP expression. UVC is capable of strongly
activating the mouse CHOP promoter in stably transfected NIH 3T3 cells but has
only a modest and transient effect on the level of the CHOP messenger RNA. In
addition to its positive effect on CHOP promoter activity, we show that UVC
negatively affects CHOP mRNA and protein expression. Pretreatment of NIH 3T3
cells with UVC markedly attenuates the subsequent induction of CHOP mRNA by the
cellular stress activators methylmethane sulfate, tunicamycin, glucose
deprivation, and methionine deprivation for as long as at least 16 h. This
inhibitory effect of UVC on CHOP expression in response to stress is independent
of the presence or absence of p53 and does not involve mRNA degradation as
opposed to the UVC effect that inhibits p21 expression seen only in the absence
of p53. The target of the inhibitory effect of UVC on CHOP expression is located
in the first exon of the gene, a 5'-untranslated region that is unusually
conserved between different species. These findings suggest that an unknown
function encoded by the 5'-untranslated region somehow modifies the response of
CHOP gene transcription to UVC.
PMID- 11010972
TI - BCR/ABL regulates expression of the cyclin-dependent kinase inhibitor p27Kip1
through the phosphatidylinositol 3-Kinase/AKT pathway.
AB - Deregulation of cell cycle checkpoints is an almost universal abnormality in
human cancers and is most often due to loss-of-function mutations of tumor
suppressor genes such as Rb, p53, or p16(INK4a). In this study, we demonstrate
that BCR/ABL inhibits the expression of a key cell cycle inhibitor, p27(Kip1), by
signaling through a pathway involving phosphatidylinositol 3-kinase (PI3K).
p27(Kip1) is a widely expressed inhibitor of cdk2, an essential cell cycle kinase
regulating entry into S phase. We demonstrate that the decrease of p27(Kip1) is
directly due to BCR/ABL in hematopoietic cells by two different approaches.
First, induction of BCR/ABL by a tetracycline-regulated promoter is associated
with a reversible down-regulation of p27(Kip1). Second, inhibition of BCR/ABL
kinase activity with the Abl tyrosine kinase inhibitor STI571 rapidly increases
p27(Kip1) levels. The PI3K inhibitor LY-294002 blocks the ability of BCR/ABL to
induce p27(Kip1) down-regulation and inhibits BCR/ABL-induced entry into S phase.
The serine/threonine kinase AKT/protein kinase B is a known downstream target of
PI3K. Transient expression of an activated mutant of AKT was found to decrease
expression of p27(Kip1), even when PI3K was inhibited by LY-294002. The mechanism
of p27(Kip1) regulation is primarily related to protein stability, since
inhibition of proteasome activity increased p27(Kip1) levels in BCR/ABL
transformed cells, whereas very little change in p27 transcription was found.
Overall, these data are consistent with a model in which BCR/ABL suppresses
p27(Kip1) protein levels through PI3K/AKT, leading to accelerated entry into S
phase. This activity is likely to explain in part previous studies showing that
activation of PI3K was required for optimum transformation of hematopoietic cells
by BCR/ABL in vitro and in vivo.
PMID- 11010974
TI - Multiprotein complex formation at the beta myosin heavy chain distal muscle CAT
element correlates with slow muscle expression but not mechanical overload
responsiveness.
AB - To examine the role of the beta-myosin heavy chain (betaMyHC) distal muscle CAT
(MCAT) element in muscle fiber type-specific expression and mechanical overload
(MOV) responsiveness, we conducted transgenic and in vitro experiments. In adult
transgenic mice, mutation of the distal MCAT element led to significant
reductions in chloramphenicol acetyltransferase (CAT) specific activity measured
in control soleus and plantaris muscles when compared with wild type transgene
beta293WT but did not abolish MOV-induced CAT specific activity. Electrophoretic
mobility shift assay revealed the formation of a specific low migrating nuclear
protein complex (LMC) at the betaMyHC MCAT element that was highly enriched only
when using either MOV plantaris or control soleus nuclear extract. Scanning
mutagenesis of the betaMyHC distal MCAT element revealed that only the
nucleotides comprising the core MCAT element were essential for LMC formation.
The proteins within the LMC when using either MOV plantaris or control soleus
nuclear extracts were antigenically related to nominal transcription enhancer
factor 1 (NTEF-1), poly(ADP-ribose) polymerase (PARP), and Max. Only in vitro
translated TEF-1 protein bound to the distal MCAT element, suggesting that this
multiprotein complex is tethered to the DNA via TEF-1. Protein-protein
interaction assays revealed interactions between nominal TEF-1, PARP, and Max.
Our studies show that for transgene beta293 the distal MCAT element is not
required for MOV responsiveness but suggest that a multiprotein complex likely
comprised of nominal TEF-1, PARP, and Max forms at this element to contribute to
basal slow fiber expression.
PMID- 11010975
TI - Germ-free and colonized mice generate the same products from enteric
prodefensins.
AB - The use of germ-free mice offers the possibility to study antibacterial
components in a gut uncolonized by bacteria. We have developed a method to
extract and high pressure liquid chromatography-fractionate the antibacterial
factors present in the small intestine of a single mouse. By mass spectrometry
and sequence analyses of fractions exhibiting antimicrobial activity, we
identified and characterized the defensin region in germ-free mice as well as in
colonized mice. Defensins made up around 15% of the total antibacterial activity
both in germ-free and colonized mice. The intestine of germ-free mice exhibited
the same set of mature enteric defensins (defensins 1, 2, 3, 4, and 6) as mice
colonized by a normal microflora. Mature defensins are generated through
processing of larger precursors by enzymatic removal of a signal peptide and a
propiece. We found that all prodefensins were cleaved at a Ser/Ala-Leu bond,
giving 34-residue propiece peptides and only trace amounts of the predicted 39
residue peptide. This first step must be followed by the removal of a residual
peptide to render the mature defensins, indicating that the processing is more
complex than previously anticipated. The same propieces were found in both germ
free and colonized mice, suggesting that the same processing operates independent
of bacterial presence in the intestine.
PMID- 11010976
TI - Differential activation of p38 mitogen-activated protein kinase isoforms
depending on signal strength.
AB - We have investigated the ability of the mitogen-activated protein kinase (MAPK)
kinase MKK6 to activate different members of the p38 subfamily of MAPKs and found
that some MKK6 mutants can efficiently activate p38alpha but not p38gamma. In
contrast, a constitutively active MKK6 mutant activated both p38 MAPK isoforms to
similar extents. The same results were obtained upon co-expression in Xenopus
oocytes and in vitro using either MKK6 immunoprecipitates from transfected cells
or bacterially produced recombinant proteins. We also found that the preferential
activation of p38alpha by MKK6 correlated with more efficient binding of MKK6 to
p38alpha than to p38gamma. Furthermore, increasing concentrations of
constitutively active MKK6 differentially activated either p38alpha alone (low
MKK6 activity) or both p38alpha and p38gamma (high MKK6 activity), both in vitro
and in injected oocytes. The determinants for selectivity are located at the
carboxyl-terminal lobe of p38 MAPKs but do not correspond to the activation loop
or common docking sequences. We also showed that different stimuli can induce
different levels of endogenous MKK6 activity that correlate with differential
activation of p38 MAPKs. Our results suggest that the level of MKK6 activity
triggered by a given stimulus may determine the pattern of downstream p38 MAPK
activation in the particular response.
PMID- 11010977
TI - NMR analysis of type III antifreeze protein intramolecular dimer. Structural
basis for enhanced activity.
AB - The structure of a new antifreeze protein (AFP) variant, RD3, from antarctic eel
pout (Rhigophila dearborni) with enhanced activity has been determined for the
first time by nuclear magnetic resonance spectroscopy. RD3 comprises a unique
translational topology of two homologous type III AFP globular domains, each
containing one flat, ice binding plane. The ice binding plane of the N domain is
located approximately 3.5 A "behind" that of the C domain. The two ice binding
planes are located laterally with an angle of 32 +/- 12 degrees between the
planes. These results suggest that the C domain plane of RD3 binds first to the
ice [1010] prism plane in the <0001> direction, which induces successive ice
binding of the N domain in the <0101> direction. This manner of ice binding
caused by the unique structural topology of RD3 is thought to be crucial for the
significant enhancement of antifreeze activity, especially at low AFP
concentrations.
PMID- 11010978
TI - Modulation of amyloid precursor protein metabolism by X11alpha /Mint-1. A
deletion analysis of protein-protein interaction domains.
AB - Modulation of amyloid precursor protein (APP) metabolism plays a pivotal role in
the pathogenesis of Alzheimer's disease. The phosphotyrosine-binding/protein
interaction (PTB/PI) domain of X11alpha, a neuronal cytosolic adaptor protein,
binds to the YENPTY sequence in the cytoplasmic carboxyl terminus of APP. This
interaction prolongs the half-life of APP and inhibits Abeta40 and Abeta42
secretion. X11alpha/Mint-1 has multiple protein-protein interaction domains, a
Munc-18 interaction domain (MID), a Cask/Lin-2 interaction domain (CID), a PTB/PI
domain, and two PDZ domains. These X11alpha protein interaction domains may
modulate its effect on APP processing. To test this hypothesis, we performed a
deletion analysis of X11alpha effects on metabolism of APP(695) Swedish
(K595N/M596L) (APP(sw)) by transient cotransfection of HEK 293 cells with: 1)
X11alpha (X11alpha-wt, N-MID-CID-PTB-PDZ-PDZ-C), 2) amino-terminal deletion
(X11alpha-DeltaN, PTB-PDZ-PDZ), 3) carboxyl-terminal deletion (X11alpha-DeltaPDZ,
MID-CID-PTB), or 4) deletion of both termini (PTB domain only, PTB). The carboxyl
terminus of X11alpha was required for stabilization of APP(sw) in cells. In
contrast, the amino terminus of X11alpha was required to stimulate APPs
secretion. X11alpha, X11alpha-DeltaN, and X11alpha-PTB, but not X11alpha
DeltaPDZ, were effective inhibitors of Abeta40 and Abeta42 secretion. These
results suggest that additional protein interaction domains of X11alpha modulate
various aspects of APP metabolism.
PMID- 11010979
TI - Lead poisoning.
PMID- 11010980
TI - Dysfunctional voiding.
PMID- 11010981
TI - Back to basics: host responses to infection.
PMID- 11010982
TI - Earning CME credit-completing the PIR quiz
PMID- 11010983
TI - The child and death.
PMID- 11010985
TI - Treatment of antibody deficiency syndromes.
PMID- 11010986
TI - Message from the Incoming Editor.
PMID- 11010987
TI - A Tribute to Paul Green.
PMID- 11010988
TI - New Evidence for the Role of Mechanical Forces in the Shoot Apical Meristem.
AB - The mechanism for initiation of lateral organs in the shoot apical meristem is
still unknown. In this article we investigate one critical component of a
buckling mechanism of organ initiation (that is, the presence and distribution of
compressive stresses in the meristem). Direct evidence for compression in the
sunflower capitulum was obtained from the gaping pattern of shallow cuts and the
propagation of fractures. Cuts gaped widely in the central region of the
capitulum but remained closed, or nearly so, in the generative and
differentiation regions, suggesting the presence of circumferential compression
at these locations. Fractures were initiated in the generative region and
propagated circumferentially over most of their length. They did not cross the
generative region perpendicularly, suggesting again the presence of compressive
stresses in the circumferential direction. This conclusion was confirmed by the
stress distribution computed from the geometry of the capitulum at three stages
of development. One interpretation of these results is that the generative region
corresponds to a zone of compression that could control the initiation of new
primordia by means of buckling of the tunica layer.
PMID- 11010989
TI - Leaves as Shell Structures: Double Curvature, Auto-Stresses, and Minimal
Mechanical Energy Constraints on Leaf Rolling in Grasses.
AB - Grass leaves are natural examples of shell structures because they are thin and
display a double curvature. An important mechanical property of shells is that
changes in longitudinal and transverse curvatures are not independent. The basis
of this mechanical coupling is presented using simple diagrams. The relevance of
the structural constraints for the processes of hydronastic rolling and
developmental unrolling in grass leaves is then reviewed. I show that mechanical
constraints can explain a large part of the genetic and developmental variability
of hydronastic rolling in grasses, without reference to specific anatomic
features such as bulliform cells. Mechanical analysis of a rolled maize mutant
also revealed that developmental unrolling is not limited to a pure transverse
expansion of hinge cells and involves both longitudinal and transverse
dimensional changes in the upper epidermis. Interest in using mechanical models
as a tool to reveal structural interactions at the tissue and organ level is
discussed, and the importance of Paul Green's biophysical approach to the study
of plant morphogenesis is emphasized.
PMID- 11010990
TI - Tensile Tissue Stress Affects the Orientation of Cortical Microtubules in the
Epidermis of Sunflower Hypocotyl.
AB - In turgid multicellular organs, it is convenient to differentiate between the two
kinds of tensile forces acting in cell walls as a result of turgor pressure. The
primary forces occur both in situ and in cells isolated from the organ, whereas
the secondary forces occur only in situ. The latter are an unavoidable physical
consequence of the variation in mechanical parameters of tissues forming layers
or strands. The most rigid tissue is under maximal tensile force, whereas the
least rigid is under maximal compressive force. These forces cause tissue
stresses (that is, certain tissues are under tensile stress, whereas others are
under compressive stress in the organ). The primary and secondary forces result
in primary and secondary stress in cell walls, respectively. The anisotropy of
the primary stress is a function of cell shape. For instance, in cylindric cells
the anisotropy expressed as the ratio of longitudinal to transverse stresses is
0.5. The anisotropy of the secondary stress is a function of the compound
structure of the organ. For example, in the epidermis of sunflower hypocotyl, the
longitudinal secondary stress is much higher than the transverse stress. The
primary and secondary stresses are superimposed, and, as a consequence, the
stress anisotropy in the outer thick walls of epidermal cells is greater than 1.
These outer epidermal walls transmit most of the tissue stress. When the
epidermis is peeled but remains turgid, only primary stress remains, but loading
of the peel can reestablish the original stress anisotropy. We studied the effect
of stress anisotropy changes on the orientation of cortical microtubules (CMTs)
in the sunflower hypocotyl epidermis. We showed that changes in stress anisotropy
cause the CMT orientation to change in the direction of maximal wall stress. In
situ, the relatively high tensile tissue stress in the epidermis causes maximal
stress in the longitudinal direction and relatively steep CMT orientation. When
the tissue stress is removed from the epidermis by peeling, the CMTs tend to
reorient toward the transverse direction, which is the direction of maximal
stress in the primary component. On application of external longitudinal stress,
to substitute for tissue stress, CMTs tend to reorient in the longitudinal
direction. However, a relatively high rate of plastic strain is caused by the
stress applied to the peel in an acid medium. This produces a less steep
orientation of CMTs. It appears that the change in stress anisotropy orients the
CMT in the direction in which the stress is maximal after the change, but there
is also some effect of the growth rate on the orientation.
PMID- 11010991
TI - Co-Ordination of Cell Division and Tissue Expansion in Sunflower, Tobacco, and
Pea Leaves: Dependence or Independence of Both Processes?
AB - Temporal analyses of cell division and tissue expansion in pea, tobacco, and
sunflower leaves reveal that both processes follow similar patterns during leaf
development. Relative cell division and relative tissue expansion rates are
maximal and constant during early leaf development, but they decline later. In
contrast, relative cell expansion rate follows a bell-shaped curve during leaf
growth. Cell division and tissue expansion have common responses to temperature,
intercepted radiation, and water deficit. As a consequence, final leaf area and
cell number remain highly correlated throughout a large range of environmental
conditions for these different plant species, indicating that cell division and
tissue expansion are co-ordinated during leaf development. This co-ordination
between processes has long been explained by dependence between both processes.
Most studies on dicotyledonous leaf development indicate that leaf expansion rate
depends on the number of cells in the leaf. We tested this hypothesis with a
large range of environmental conditions and different plant species. Accordingly,
we found a strong correlation between both absolute leaf expansion rate and leaf
cell number. However, we showed that this relationship is not necessarily causal
because it can be simulated by the hypothesis of independence between cell
division and tissue expansion according to Green's theory of growth (1976).
PMID- 11010992
TI - Clonal Analysis Provides Evidence for Transient Initial Cells in Shoot Apical
Meristems of Seed Plants.
AB - Drift of mutated sectors in sectorial or mericlinal plant chimeras has been
interpreted as indirect evidence of initial impermanence at the apex. However,
the same effect may result from mutation in noninitial cells positioned close to
the vertex of the apical dome. Clonal analysis of the cell packets present in the
superficial layer of spruce and magnolia apices provided the library of patterns
suggesting that the position and the number of initial cells, and in some cases
also the meristem axis inclination, may change over time. Multicellular clones
originating from a single cell have been found in the geometric center of some
apices, whereas in other apices the cellular center (where three or four clonal
borders meet) did not correspond to the geome
PMID- 11010993
TI - Effect of Soil pH on Growth and Cation Deposition in the Root Tip of Zea mays L.
AB - The effects of sandy soil pH on the distribution of growth velocities and on
cation concentrations and deposition rates in root growth zones of Zea mays L.
seedlings were investigated. The pH values of the rooting medium varied between
4.2 and 8.6 in sand culture (70% saturated) without external supply of nutrients.
At all pH values, densities (in umoles per g fresh weight) of potassium,
magnesium, and calcium increased toward the root tip. Lower pH in the medium
increased calcium tissue density fivefold and magnesium density 1.7-fold, whereas
the density of potassium, the overall elongation rate, and the growth velocity
distribution did not show any significant pH dependence. Throughout the growth
zone the deposition rates of the divalent cations, as calculated on the basis of
the continuity equation, increased with lower pH. The data are consistent with
the hypothesis that the effects of pH on the cation deposition rates are due to
the increase in the divalent cation concentration of the soil solution at low pH
and that the abundant uronic acid residues of the young walls of the meristem
provide a reservoir of storage capacity for Ca and Mg under conditions of low
nutrient availability.
PMID- 11010994
TI - Comparison of Leaf Plastochron Index and Allometric Analyses of Tooth Development
in Arabidopsis thaliana.
AB - Two methods of analyses were used to investigate tooth development in serrate
(se) mutant and wild-type Columbia-1 (Col-1) Arabidopsis thaliana leaves. There
were almost twice as many teeth with deeper sinuses and two orders of toothing on
the margins of serrate compared with Columbia-1 leaves. The main objective of
this study was to test three hypotheses relative to the source of polymorphism in
tooth development: (i) Teeth share similar growth rates and initial sizes, but
the deeper teeth are initiated earlier in leaf development. (ii) Teeth share
similar timing of initiation and growth rates, but the deeper teeth have a larger
initial size. (iii) Teeth share similar timing of initiation and initial sizes,
but the deeper teeth have a faster growth rate. Leaf plastochron index (LPI) was
used as the time variable for leaf development. Results showed teeth in se were
initiated at -27 LPI, 15 plastochrons earlier than those of Col-1. Serrate leaf
expansion was biphasic, with the early phase expanding at half the relative
plastochron rate of the later phase, which equaled the constant relative
expansion rate of Col-1 leaves. Allometric analyses of tooth development obscured
the interactions between time of tooth and leaf initiation and the early phase of
leaf expansion characteristic of serrate leaves and teeth. Timing of
developmental events that allometric analysis obscured can be readily detected
with the LPI as a developmental index.
PMID- 11010995
TI - Ball tonometry: a rapid, nondestructive method for measuring cell turgor pressure
in thin-walled plant cells.
AB - In this article we describe a new method for the determination of turgor
pressures in living plant cells. Based on the treatment of growing plant cells as
thin-walled pressure vessels, we find that pressures can be accurately determined
by observing and measuring the area of the contact patch formed when a spherical
glass probe is lowered onto the cell surface with a known force. Within the
limits we have described, we can show that the load (determined by precalibration
of the device) divided by the projected area of the contact patch (determined by
video microscopy) provides a direct, rapid, and accurate measure of the internal
turgor pressure of the cell. We demonstrate, by parallel measurements with the
pressure probe, that our method yields pressure data that are consistent with
those from the pressure probe. Also, by incubating target tissues in stepped
concentrations of mannitol to incrementally reduce the turgor pressure, we show
that the pressures measured by tonometry accurately reflect the predicted changes
from the osmotic potential of the bathing medium. The advantages of this new
method over the pressure probe are considerable, however, in that we can move
rapidly from cell to cell, taking measurements every 20 s. In addition, the
nondestructive nature of the method means that we can return to the same cell
repeatedly for periodic pressure measurements. The limitations of the method lie
in the fact that it is suitable only for superficial cells that are directly
accessible to the probe and to cells that are relatively thin walled and not
heavily decorated with surface features. It is also not suitable for measuring
pressures in flaccid cells.
PMID- 11010996
TI - The Double-Water-Film Electrode: A Device for Measuring the Resistance and the
Capacitance of the Internode/Node Interface of Chara as Functions of Time and
Temperature.
AB - A "double-water-film electrode technique" has been developed for the long-term
characterization of the electrical properties across the interface between the
nodal (N) and internodal (A or B) cells and the vacuole along the length of an
internode of Chara as a function of time and temperature. The electrode unit
consisted of a pair of the water-film electrodes described elsewhere (Chilcott
1988; Chilcott and others 1983; Coster and others 1984; Lucas 1985; and Ogata
1983). The distance between two water-film probes was fixed at 1.0 cm. By
scanning the electrode unit, the spatial variations in electrical resistance and
capacitance along the longitudinal axis of Chara were observed. Analysis was
performed by applying an electrical equivalent circuit for the biomembrane
(Philippson 1921). Across the internode (-A or -B)/central nodal cells interface,
the specific parallel resistance (Rm) and the parallel capacitance (Cm) at 20
degrees C were 30 +/- 5 x 10(-3) Omegam(2) and 1.5 +/- 0.5 x 10(-1)Fm(-2) (at 30
Hz), respectively. And the series resistance, corresponding to the vacuole of the
internode was 8 x 10(-3) Omegam(2). Study of temperature dependencies of Rm and
Cm suggested that a dynamic homeostatic regulation was operating at the interface
where numerous plasmodesmata were observed with an electron microscope (Pickett
Heaps 1967; Spanswick and Costerton 1967). Assuming that the individual cylinder
of plasmodesma was filled only with cytoplasm, the number of plasmodesma per
interface was estimated at 2.6 x 10(5).
PMID- 11010997
TI - Effect of Abscisic Acid on Banana Fruit Ripening in Relation to the Role of
Ethylene.
AB - The role of abscisic acid (ABA) in banana fruit ripening was examined with the
ethylene binding inhibitor, 1-methylcyclopropene (1-MCP). ABA (0, 10(-5), 10(-4),
or 10(-3) mol/L) was applied by vacuum infiltration into fruit. 1-MCP (1 uL/L)
was applied by injecting a measured volume of stock gas into sealed glass jars
containing fruit. Fruit ripening, as judged by ethylene evolution and respiration
associated with color change and softening, was accelerated by 10(-4) or 10(-3)
mol/L ABA. ABA at 10(-5) mol/L had no effect. The acceleration of ripening by ABA
was greater at 10(-3) mol/L than at 10(-4) mol/L. ABA-induced acceleration of
banana fruit ripening was not observed in 1-MCP treated fruit, especially when
ABA was applied after exposure to 1-MCP. Thus, ABA's promotion of ripening in
intact banana fruit is at least partially mediated by ethylene. Exposure of ABA
treated fruit to 0.1 uL/L ethylene for 24 h resulted in increased ethylene
production and respiration, and associated skin color change and fruit softening.
Control fruit (no ABA) was unresponsive to similar ethylene treatments. The data
suggest that ABA facilitates initiation and progress in the sequence of ethylene
mediated ripening events, possibly by enhancing the sensitivity to ethylene.
PMID- 11010998
TI - Opiate receptor avidity is increased in rhesus monkeys following unilateral optic
tract lesion combined with transections of corpus callosum and hippocampal and
anterior commissures.
AB - Opiate receptor avidity (B(max)'/K(D)) was measured in four rhesus monkeys
following unilateral lesioning of the optic tract combined with transection of
the corpus callosum and the hippocampal and anterior commissures depriving one
hemisphere of visual input (Tract and Split), two animals with transection of
commissures only (Split), and nine healthy monkeys with positron emission
tomography (PET) and 6-deoxy-6-beta-[(18)F]fluoronaltrexone (cyclofoxy, CF), a mu
and kappa-opiate receptor antagonist. Opiate receptor avidity was found to be
significantly higher in the Tract and Split animals, only, bilaterally,
throughout the lateral cortex and in the cingulate and posterior putamen (41
117%). Ipsilateral changes were consistently greater than those contralateral,
but this asymmetry was of statistical significance only in the parietal and
occipital cortices. Cyclofoxy avidity was decreased in the medial cortex of both
the Tract and Split and Split animals ( approximately 25%). The results suggest
that opiate pathways undergo extensive alteration in response to changes in brain
functional activities brought about through hemispheric visual deprivation.
PMID- 11010999
TI - Release of synaptic zinc is substantially depressed by conventional brain slice
preparations.
AB - Research on synaptically-released zinc is frequently done in vitro with acute
brain slice preparations. We show here the in vitro hippocampal slice preparation
has two major pitfalls for zinc research. First, up to 50% of the synaptic zinc
is lost during slice cutting and/or the first 10 min of slice incubation, with
the losses being most pronounced on the edges of the slice. Second, the release
of the remaining zinc from a slice is substantially depressed (up to 50%) at the
low temperatures (32 degrees C) typically used for brain slice studies. In
concert, these effects reduce zinc release about 75% in vitro, compared to in
vivo. Implications for research on synaptically-released zinc are discussed.
PMID- 11011000
TI - Bilirubin does not modulate ionotropic glutamate receptors or glutamate
transporters.
AB - Bilirubin, a product of haemoglobin metabolism, has been suggested to damage
neurons by increasing activation of N-methyl-D-aspartate (NMDA) receptors when it
reaches high levels in the blood [15,19], as occurs in neonatal jaundice [7].
Bilirubin is also generated in the brain following synthesis of the messenger
carbon monoxide (CO) by haem oxygenase, and haem oxygenase is upregulated in
Alzheimer's disease [23]. We examined the effect of bilirubin on currents
generated by NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
(AMPA) receptors in hippocampal pyramidal cells, and on glutamate transporter
currents in retinal glial cells. Bilirubin did not modulate either receptor-gated
currents or transporter currents. These data show the negative, but important
result that bilirubin does not induce neuronal death by acting directly on NMDA
or AMPA receptors, nor indirectly by blocking glutamate uptake and raising the
extracellular concentration of glutamate.
PMID- 11011001
TI - A comparison of morphine analgesic tolerance in male and female mice.
AB - Studies comparing morphine tolerance in males and females are rare, and all
studies to date have utilized the rat. To generalize from findings with rats
morphine tolerance was investigated in male and female mice using the tail
withdrawal test. Three and 7 days of systemic morphine injections produced
significant but unequal rightward shifts in the morphine dose-response curve such
that females displayed greater increases in analgesic ED(50) values when compared
to males. In a separate experiment, males and females displayed similar
reductions in morphine analgesic sensitivity when %MPE (maximum possible effect)
and %total (area under the curve) were compared after 3 days of morphine.
Differences in initial morphine sensitivity between sexes were not observed in
either study. The data demonstrate that, in contrast to rats, female mice undergo
greater reductions in morphine analgesia relative to males following chronic
morphine, but this sex difference may depend on the method of assessing
analgesia. Furthermore, the duration and/or cumulative dose of morphine treatment
does not affect the expression of sex differences in morphine tolerance.
PMID- 11011002
TI - Intracerebroventricular met-enkephalin administration modulates adjuvant
arthritis.
AB - The purpose of this study was to investigate the anti-inflammatory properties of
intracerebroventricular met-enkephalin (met-enk) administration in an animal
model of arthritis. Adjuvant arthritis was induced in rats by intradermal
inoculation of mycobacterium butyricum and the effects of intraventricular met
enk+thiorphan (enkephalinase inhibitor) were studied. Treatment was initiated
either simultaneously with the bacterial inoculation (preventive group) or on
post-inoculation day 17 after the appearance of inflammation (treatment group).
The degree of inflammation was evaluated by measuring the diameter and the
circumference of the ankle joint immediately before the sacrifice (day 31) and by
histologic examination of ankle joint sections. The results of this study
revealed that combined intraventricular injections of met-enk+thiorphan reduced
the arthritic-like inflammation in the preventive group as well as in the
treatment group. These findings suggest that centrally applied met-enk+thiorphan
may suppress the development adjuvant arthritis as well as the symptoms of
manifest arthritis. Thus central met-enk may be involved in both hypothalamic
pituitary adrenal axis and immune forms of stress-induced modulation.
PMID- 11011003
TI - The role of intrinsic and agonist-activated conductances in determining the
firing patterns of preoptic area neurons in the guinea pig.
AB - Whole-cell and intracellular recordings were made in coronal hypothalamic slices
prepared from ovariectomized female guinea pigs. 62% of preoptic area (POA)
neurons fired action potentials in a bursting manner, and exhibited a
significantly greater afterhyperpolarization (AHP) than did non-bursting POA
neurons. The majority (70%) of POA neurons (n=76) displayed a time-dependent
inward rectification (I(h)) that was blocked by CsCl (3 mM) or by ZD 7288 (30
microM). In addition, 51% of the cells expressed a low-threshold spike (LTS)
associated with a transient inward current (I(T)) that was blocked by NiCl(2)
(200 microM). A smaller percentage of POA neurons (29%) expressed a transient
outward, A-type K(+) current that was antagonized by a high concentration of 4
aminopyridine (3 mM). Moreover, POA neurons responded to bath application of the
mu-opioid receptor agonist DAMGO (93%) or the GABA(B) receptor agonist baclofen
(83%) with a membrane hyperpolarization or an outward current. These responses
were accompanied by a decrease in input resistance or an increase in conductance,
respectively, and were attenuated by BaCl(2) (100 microM). In addition, the
reversal potential for these responses closely approximated the Nernst
equilibrium potential for K(+). These results suggest that POA neurons
endogenously express to varying degrees an AHP, an I(h), an I(T) and an A-type
K(+) current. The vast majority of these neurons also are inhibited upon mu
opioid or GABA(B) receptor stimulation via the activation of an inwardly
rectifying K(+) conductance. Such intrinsic and transmitter-activated
conductances likely serve as important determinants of the firing patterns of POA
neurons.
PMID- 11011004
TI - Neurotoxicity of HIV-1 proteins gp120 and Tat in the rat striatum.
AB - HIV-associated dementia complex is a serious disabling disease characterized by
cognitive, behavioral and motor dysfunction. Basal ganglia involvement in HIV-1
infection may be responsible for some of the psychomotor symptoms associated with
HIV dementia. The objectives of the present study were to determine: (1) whether
gp120 and Tat produce striatal toxicity, and (2) whether gp120 and Tat show
synergistic toxicity in the striatum. In these studies, the recombinant proteins
gp120, Tat, or saline (0.9%) were stereotaxically injected in the striatum of
adult male rats. The striatal sections were evaluated for area of tissue loss
(Cresyl-violet stained sections) and the number of GFAP immunoreactive cells 7
days after the injections. Doses of gp120 250 ng/microl or higher and Tat 5
microg/microl or higher produced a significant area of tissue loss and
significantly increased the number of GFAP reactive cells. We found no toxicity
in animals treated with immunoabsorbed gp120 or Tat. Combined gp120 (100
ng/microl)+Tat (1 microg/microl) injections into the rat striatum significantly
increased the area of tissue loss and altered morphology and increased number of
GFAP reactive cells, as compared to controls. Thus, the present results suggest
the involvement of gp120 and Tat in striatal toxicity and provide a model for
further studies to fully characterize their role in HIV-1 toxicity and to develop
therapeutic strategies for HIV-1 associated dementia complex.
PMID- 11011005
TI - Diadenosine polyphosphates facilitate the evoked release of acetylcholine from
rat hippocampal nerve terminals.
AB - Diadenosine polyphosphates are present in synaptic vesicles, are released upon
nerve stimulation and possess membrane receptors, namely in presynaptic
terminals. However, the role of diadenosine polyphosphates to control
neurotransmitter release in the CNS is not known. We now show that diadenosine
pentaphosphate (Ap(5)A, 3-100 microM) facilitated in a concentration dependent
manner the evoked release of acetylcholine from hippocampal nerve terminals, with
a maximal facilitatory effect of 116% obtained with 30 microM Ap(5)A. The
selective diadenosine polyphosphate receptor antagonist, diinosine pentaphosphate
(Ip(5)I, 1 microM), inhibited by 75% the facilitatory effect of Ap(5)A (30
microM), whereas the P(2) receptor antagonists, suramin (100 microM) and
pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 10 microM) only
caused a 18-24% inhibition, the adenosine A(1) receptor antagonist, 1,3-dipropyl
8-cyclopentylxanthine (20 nM), caused a 36% inhibition and the adenosine A(2A)
receptor antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo [2,3-a][1,3,
5]triazin-5-ylamino]ethyl)phenol (ZM 241385, 20 nM), was devoid of effect. These
results show that diadenosine polyphosphates act as neuromodulators in the CNS,
facilitating the evoked release of acetylcholine mainly through activation of
diadenosine polyphosphate receptors.
PMID- 11011006
TI - Short-term ethanol exposure alters calbindin D28k and glial fibrillary acidic
protein immunoreactivity in hippocampus of mice.
AB - The effects of a short-term ethanol treatment on hippocampus have been studied in
mice exhibiting intoxication signs. The alterations of neurons and astrocytes as
well as quantitative changes of calbindin D28k-immunoreactivity and glial
fibrillary acidic protein-immunoreactivity (GFAP-IR) in selected regions of the
dorsal hippocampus were examined using anti-calbindin and anti-GFAP monoclonal
anti-body (mAb), respectively. The administration of 6% (v/v) ethanol during
first week led to the neuronal death and decrease of the total number of
calbindin-IR neurons in the examined brain regions. Moreover, the calbindin
positive neurons were shown to have diminished processes following short-term
ethanol exposure. These neuronal changes were associated with the increase of the
GFAP-IR astrocytes. Hypertrophy of cell bodies and cytoplasmic processes of
reactive astrocytes were also seen. In addition, dense, thick and highly-stained
GFAP-IR cells with long processes in granular cell layer appeared entering into
molecular layer of dentate gyrus. In agreement with the discrepancy percentage of
neuronal cell loss and increase of reactive astrocytes detected by calbindin and
GFAP-IR using image quantitative analysis, the regional differences in the
vulnerability to the neurotoxic effects following short-term ethanol exposure
were found: CA3>CA2>CA1>DG. These findings also illustrate the importance of
correlation between calbindin and GFAP-IR when determining the morphological
alteration of neuron and astroglial following short-term ethanol treatment. The
disruption of calbindin and GFAP could affect neuronal-astroglial interaction,
resulting in disturbance of behaviors dependent on hippocampus.
PMID- 11011007
TI - Effects of threonine injections in the lateral hypothalamus on intake of amino
acid imbalanced diets in rats.
AB - Previous work from this laboratory suggests that animals decrease their intake of
an amino acid imbalanced diet (IMB), due in part to a drop in the concentration
of the dietary limiting amino (DLAA) in the anterior piriform cortex (APC).
Administration of the DLAA, but not of a non-limiting amino acid into the APC,
blocks the anorectic response to IMB. To our knowledge, the effects of DLAA
injections on intake of a diet devoid of the DLAA (DEV), have not been examined
in areas outside the APC. We hypothesized that the LH is a potential chemosensory
area for DLAA. Our objectives were: (1) to determine whether injections of the
DLAA threonine into the lateral hypothalamus (LH) alter intake of a threonine
devoid diet (DEV); and (2) to examine the dose-response effects of threonine
injections into the LH on intake of threonine-corrected diet (COR).
Administration of threonine into the LH stimulated DEV intake during the first 6
h at the 0.25 and 1-nmol doses by approximately 26 and 24%, respectively.
Threonine (0.25, 2.5 nmol) did not alter COR intake at any time during the first
12 h. Our results suggest that: (1) the LH, along with the APC, likely acts as a
chemosensory brain area for indispensable amino acids; and (2) both the APC and
LH are part of a circuit that is involved in the short term anorectic response to
amino acid imbalanced diets.
PMID- 11011008
TI - Odor input generates approximately 1.5 Hz and approximately 3 Hz spectral peaks
in the helix pedal ganglion.
AB - In 1999 we reported that odorants evoke in the Helix pedal ganglion (PG) activity
patterns which are largely odorant-specific and related to the nature of odor and
its behavioral output. Notably, some activities (for example, approximately 1.5
and approximately 3 Hz), nonspecific to odorants, were consistently evoked in PG.
The present contribution goes farther in a deeper survey of the intrinsic and
odorant-evoked activities of PG with special weight on the nonspecific
fluctuations. We address the following questions. (i) What are the features of
the activities? (ii) Are they comparable to the activities found in the motor
systems of the other invertebrates? (iii) To what functions can they be related?
Three main frequency components represented by power peaks at <1 Hz, 1-2 Hz and 2
8 Hz seem to feature the response activities of PG. (a) The aversive odorants
induce odorant-specific patterns represented by peak power frequencies at <1 Hz.
(b) The oscillation at approximately 1 Hz, which exists intrinsically in the
Helix PG, can be specifically enhanced by appetitive odors. Activities induced in
the procerebrum (PC), the visceral ganglion (VG) and PG by appetitive odorants,
such as ethanol and apple, peak at 1.3-2 Hz, whereas those induced by aversive
ones, such as formic acid and onion at <1 Hz. (c) The 2-8 Hz components always
accompany the odorant-evoked activities of the PG either as the second or third
strongest component, or in the form of conspicuous, long-lasting approximately 3
Hz oscillations. (d) The nonspecific odor-evoked 1-2 Hz and approximately 3 Hz
activities, and the intrinsic approximately 1 Hz activity of the PG seem to be
interrelated by a degree of mutual exclusion. We may therefore consider these
activities as elementary, slow components that are involved in the processing of
signals in this ganglion. It can be inferred from the findings in other
invertebrates that the 1-3 Hz spontaneous discharge is strongly connected with
motor activity that involves the feedback mechanism of the procerebro-cerebro
buccal or -procerebro-cerebro-pedal circuit. Our approach differs from most
others reported so far in the following aspects: (i) use of gross steel
electrodes for recording population activities; (ii) lengthy stimulation (10
min); (iii) long observation during and after stimulation; (iv) power spectral
presentation of temporal evolution of activity patterns; (v) estimation of peak
power frequency by Frequency-Amplitude Plot (FAP) (obtained from signals averaged
in the frequency domain; a method based on systems theory).
PMID- 11011009
TI - Quisqualate induces an inward current via mGluR activation in neocortical
pyramidal neurons.
AB - Activation of metabotropic glutamate receptors (mGluRs) has multiple effects on
the excitability of pyramidal neurons in rat frontal neocortex. Synaptic
transmission and intrinsic excitability are both affected. During studies of the
effects of quisqualate on synaptic activity, it was observed that quisqualate
also induced a slow inward current. Whole-cell patch clamp recordings were
obtained from layer II/III pyramidal neurons of neocortical slices in vitro. The
bath solution contained APV, CNQX and bicuculline to block ionotropic glutamate
and GABA(A) receptors. At a holding potential of -70 mV, quisqualate (2 microM)
induced an inward current of about 60 pA. The response was reversible upon
washing. This current was associated with an increase in membrane conductance and
was still seen in the presence of TTX (0.5 microM). Bath application of the
nonselective mGluR antagonist, (R, S)-alpha-methyl-4-carboxyphenyglycine (MCPG,
200-500 microM) reduced the current by 70%. Other mGluR agonists (ACPD, DHPG, L
CCG-1 and L-AP4) did not induce a significant inward current at the
concentrations tested. The current-voltage relation of the quisqualate-induced
current was linear with a reversal potential near 0 mV suggesting involvement of
nonselective cation channels. The quisqualate-induced inward current was markedly
reduced (72%) with 200 microM GDP-beta-S in the pipette solution, indicating that
it is a postsynaptic phenomenon mediated by a G-protein dependent mechanism.
These results suggest that mGluRs can directly increase the postsynaptic
excitability of pyramidal cells.
PMID- 11011010
TI - Enhancement of the acoustic startle response by dopamine agonists after 6
hydroxydopamine lesions of the substantia nigra pars compacta: corresponding
changes in c-Fos expression in the caudate-putamen.
AB - Rats with 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway show
enhanced locomotor and stereotyped behaviors when challenged with direct and
indirect dopamine (DA) agonists due to the development of postsynaptic
supersensitivity. To determine if this phenomenon generalizes to other motor
behaviors, we have used this rat model of Parkinson's disease to examine the
effects of the direct dopamine D(1) receptor agonist SKF 82958 and the indirect
DA agonist L-3,4-dihydroxyphenylalanine (L-DOPA) on the acoustic startle
response. In addition, we used the expression of c-Fos protein as a marker of
neuronal activity to assess any corresponding drug-induced changes in the caudate
putamen (CPu) after L-DOPA administration. Male Sprague-Dawley rats received
bilateral injections of 6-OHDA into the substantia nigra pars compacta and 1 week
later were tested for startle after systemic administration of SKF 82958 (0.05
mg/kg) or L-DOPA (1, 5, 10 mg/kg). SKF 82958 produced a marked enhancement of
startle with a rapid onset in 6-OHDA-lesioned but not SHAM animals. L-DOPA
produced a dose- and time-dependent enhancement of startle in 6-OHDA-lesioned
rats that had no effect in SHAM animals even at the highest dose (10 mg/kg).
Furthermore, L-DOPA produced a dramatic induction of c-Fos in the CPu in 6-OHDA
lesioned animals. Consistent with other literature, these data suggest that
neurons in the CPu become supersensitive to the effects of DA agonists after 6
OHDA-induced denervation of the nigrostriatal pathway and that supersensitive
dopamine D(1) receptors may mediate the enhancement of startle seen in the
present study.
PMID- 11011011
TI - Autonomic and cardiovascular reflex responses to central estrogen injection in
ovariectomized female rats.
AB - The role of estrogen in central autonomic nuclei was examined in ovariectomized
female Sprague-Dawley rats supplemented daily for 7 days with either estrogen (5
microg/kg; sc) or saline (0.9%; sc). Animals were subsequently anaesthetized with
sodium thiobutabarbital (Inactin; 100 mg/kg; ip) and instrumented to record blood
pressure and heart rate. Efferent vagal parasympathetic (VPNA) and renal
sympathetic (RSNA) nerve activities were recorded and used to assess baseline and
reflexive changes in autonomic tone. The cardiac baroreflex was evoked using a
single bolus injection of phenylephrine (0.1 mg/kg) both before and following
either intrathecal injection of estrogen (0.5 microM; 1 microl) or bilateral
injection of estrogen (0.5 microM; 100 nl/side) into several central autonomic
nuclei. In estrogen-replaced rats, both the baseline and PE-evoked values for
mean arterial pressure and RSNA were significantly decreased following injection
of estrogen into the nucleus tractus solitarius (NTS), rostral ventrolateral
medulla (RVLM), parabrachial nucleus (PBN), central nucleus of the amygdala (CNA)
and the intrathecal space. Baseline heart rate and VPNA were significantly
decreased following injection of estrogen into NTS, nucleus ambiguous (Amb), PBN
and the intrathecal space. PE-evoked changes in heart rate and VPNA were
significantly enhanced following injection of estrogen into these same nuclei.
Injection of estrogen into the insular cortex (IC) produced significant decreases
in baseline and PE-evoked RSNA only. The cardiac baroreflex was significantly
enhanced following injection of estrogen into all nuclei and the intrathecal
space. In saline-replaced females, injection of estrogen into NTS, RVLM, Amb and
the intrathecal space had similar effects on both baseline and PE-evoked
parameters although of a reduced magnitude compared to estrogen-replaced rats.
However, no significant changes in autonomic tone and baroreflex function were
observed following the injection of estrogen into the PBN, CNA or IC of saline
replaced rats. These results demonstrate a role for estrogen in central autonomic
nuclei in female rats and suggest a possible alteration of estrogen receptor
distribution or efficacy within the central nervous system of estrogen-deficient
female rats.
PMID- 11011013
TI - Haemodynamic correlates of penumbral depolarization following focal cerebral
ischaemia.
AB - Transient ischaemic depolarizations (IDs) are thought to play a key role in the
pathogenesis of focal cerebral ischaemia. Most transient IDs are akin to
spreading depression (SD), although a negative DC shift is not observed in half
the cases. The other IDs may represent transient anoxic depolarizations. Using
cortical DC and blood flow recordings, following middle cerebral artery occlusion
in rats, we show here that: (i) these later depolarizations do indeed represent
transient anoxic depolarizations; (ii) SD-like IDs, DC and haemodynamic
parameters are similar to those of SDs when blood flow remains close to base line
and; (iii) when blood flow decreases, the hyperaemia associated with SD-like IDs
is largely reduced and there is an increasing proportion of cortical sites which
fail to display a DC shift. These data demonstrate the coexistence of two
mechanisms of IDs, and yield new information as to the flow-dependence of DC and
haemodynamic correlates of SD-like IDs, the pathophysiological significance of
which remains to be determined.
PMID- 11011012
TI - The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier.
AB - L-DOPA is transported across the blood-brain barrier (BBB) by an amino acid
transporter, system L. Recently, it has been demonstrated that system L consists
of two subunits, 4F2hc and either LAT1 or LAT2. 4F2hc/LAT1 and 4F2hc/LAT2 show
different transport characteristics, while their distribution in the brain has
not been determined. To clarify whether 4F2hc/LAT1 participates in L-DOPA
transport across the BBB, we first examined the expression of 4F2hc/LAT1 in the
mouse brain capillary endothelial cell line, MBEC4, as an in vitro BBB model.
Northern hybridization and immunoblotting revealed that both 4F2hc and LAT1 are
expressed and form a heterodimer in MBEC4 cells. To confirm whether 4F2hc/LAT1
acts as system L to transport L-DOPA, we characterized L-DOPA uptake into the
cells. The uptake process was time-dependent, temperature-sensitive, and Na(+)
independent. Neutral amino acids with bulky side chains and a bicyclic amino
acid, 2-aminobicyclo-[2, 2,1]-heptane-2-carboxylic acid (BCH), inhibited L-DOPA
uptake into MBEC4 cells to a great extent, while an acidic amino acid, basic
amino acids, and glycine had no effect. Other neutral amino acids, such as
alanine, asparagine, glutamine, serine, and threonine inhibited L-DOPA uptake by
40-70% at most. These characteristics are more compatible with those of
4F2hc/LAT1, rather than those of 4F2hc/LAT2. Finally, immunohistochemistry with
anti-LAT1 antibody demonstrated that LAT1 is predominantly expressed in the
microvessels of the central nervous system. This is the first report showing that
the 4F2hc/LAT1 complex participates in L-DOPA transport across the BBB.
PMID- 11011014
TI - Effects of amygdala lesions on sleep in rhesus monkeys.
AB - The amygdala is important in processing emotion and in the acquisition and
expression of fear and anxiety. It also appears to be involved in the regulation
of sleep and wakefulness. The purpose of this study was to assess the effects of,
fiber-sparing lesions of the amygdala on sleep in rhesus monkeys (Macaca
mulatta). We recorded sleep from 18 age-matched male rhesus monkeys, 11 of which
had previously received ibotenic acid lesions of the amygdala and seven of which
were normal controls. Surface electrodes for sleep recording were attached and
the subjects were seated in a restraint chair (to which they had been adapted)
for the nocturnal sleep period. Despite adaptation, control animals had sleep
patterns characterized by frequent arousals. Sleep was least disrupted in animals
with large bilateral lesions of the amygdala. They had more sleep and a higher
proportion of rapid-eye-movement (REM) sleep than did either animals with smaller
lesions or control animals. Based on these results, it seems likely that, in the
primate, the amygdala plays a role in sleep regulation and may be important in
mediating the effects of emotions/stress on sleep. These findings may also be
relevant to understanding sleep disturbances associated with psychopathology.
PMID- 11011015
TI - Ovarian steroids influence the activity of neuroendocrine dopaminergic neurons.
AB - The secretion of prolactin (PRL) from the anterior lobe (AL) of the pituitary
gland is tonically inhibited by dopamine (DA) of hypothalamic origin. While
ovarian steroids play a role in the regulation of the secretion of PRL, their
effect on all three populations of hypothalamic neuroendocrine dopaminergic
neurons is not fully understood. In this study we describe the effects of ovarian
steroids on regulation of the release of DA from tuberoinfundibular dopaminergic
(TIDA), tuberohypophyseal dopaminergic (THDA) and periventricular-hypophyseal
dopaminergic (PHDA) neurons. Adult female rats were bilaterally ovariectomized
(OVX) and, 10 days following ovariectomy (day 0), injected with corn oil
(vehicle), estrogen, or estrogen plus progesterone (day 1). Animals were
sacrificed every 2 h from 09.00 to 21.00 h by rapid decapitation. Trunk blood was
collected and the concentration of PRL in serum was determined by
radioimmunoassay. The median eminence (ME) and the AL, intermediate (IL) and
neural (NL) lobes of the pituitary gland were dissected and the concentration of
DA and DOPAC in each was measured by HPLC-EC. OVX rats presented small but
significant increases in the secretion of PRL at 15.00 and 17.00 h. Replacement
of estrogen or estrogen plus progesterone increased the basal concentration of
PRL. Moreover, injection of estrogen only, or estrogen plus progesterone
increased the concentration of PRL in serum at 15.00 h through 19.00 h,
respectively, followed by a decrease to baseline thereafter. The turnover of DA
in the ME and NL of OVX rats increased at 13.00 and returned to low levels.
Turnover of DA in the IL of OVX rats increased in the morning by 11.00 h and
remained elevated before decreasing by 17.00 h. The turnover of DA in the ME, IL
and NL of OVX rats increased by 19.00 h. Injection of estrogen advanced the
increase of TIDA activity by 2 h in the ME compared to OVX rats. Moreover,
administration of estrogen suppressed the activity of THDA and PHDA neurons in
the afternoon compared to OVX rats. In estrogen plus progesterone-treated rats,
the activity of hypothalamic neuroendocrine dopaminergic neurons terminating in
the ME, IL, and NL was inhibited prior to the increase in the secretion of PRL.
The concentration of DA in the AL diminished prior to the estrogen-induced
increase of PRL. Administration of progesterone, in concert with estrogen,
delayed the increase of PRL in serum and the decrease of DA in the AL, compared
to estrogen-treated rats, by 4 h. These data suggest a major role for ovarian
steroids in controlling increases in the secretion of PRL by not only stimulating
PRL release from lactotrophs, but also by inhibiting the activity of all three
populations of hypothalamic neuroendocrine DAergic neurons.
PMID- 11011016
TI - The effects of L-NAME on vestibular compensation and NOS activity in the
vestibular nucleus, cerebellum and cortex of the guinea pig.
AB - Nitric oxide (NO) has been implicated in the processes by which animals recover
from peripheral vestibular damage ('vestibular compensation'). However, few data
exist on the dose-response effects of systemic administration of the nitric oxide
synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on the
vestibular compensation process. The aim of this study was to investigate the
effects on compensation of 5, 10, 50 or 100 mM L-NAME administered by s.c osmotic
minipump for 50 h following unilateral vestibular deafferentation (UVD) in guinea
pig, either commencing the drug treatment at 4 h pre-UVD or at the time of the
UVD (i.e., post-UVD). Post-UVD treatment with L-NAME, at any of the four
concentrations used, had no effect on the compensation of spontaneous nystagmus
(SN), yaw head tilt (YHT) or roll head tilt (RHT). By contrast, pre-UVD treatment
with 100 mM L-NAME resulted in a significant decrease in SN frequency (P<0.05)
and a change in the rate of its compensation (P<0.0005). Pre-UVD L-NAME resulted
in a significant increase in the overall magnitude of YHT (P<0.005); however,
post-hoc comparisons revealed no significant differences between any specific L
NAME and vehicle groups. Pre-UVD L-NAME had no effect on RHT at any
concentration. Analysis of NOS activity in the pre-UVD L-NAME treatment groups at
50 h post-UVD showed that only 100 mM L-NAME resulted in a significant decrease
in NOS activity in the contralateral medial vestibular nucleus (MVN)/prepositus
hypoglossi (PH) (P<0.05) and that NOS activity in the ipsilateral MVN/PH was not
significantly affected. However, NOS activity was significantly inhibited in the
bilateral cerebellum and cortices for several concentrations of L-NAME. These
results suggest that pre-UVD systemic administration of L-NAME can significantly
increase the rate of SN compensation in guinea pig and that this effect is
correlated with inhibition of NOS activity in several regions of the CNS.
PMID- 11011017
TI - Behavioral training-induced c-Fos expression in the rat nucleus basalis of
Meynert during aging.
AB - The present study investigated the behavioral training-induced c-Fos expression
in the nucleus basalis of Meynert (nbM) in differently aged rats. This study
demonstrated that the c-Fos expression in nbM was significantly increased and the
peak occurred at 2 h after dark-avoidance training. Although the increase of c
Fos expression was also observed after pseudotraining, the number of Fos-like
immunoreactive neurons in pseudotrained rats was significantly less than that in
dark-avoidance trained rats at each time-point. This result suggested that c-Fos
expression might be involved in learning and memory processes. In addition, all
the pseudotraining-, training- and memory arousing-induced c-Fos expression was
decreased with increasing age, and the decrease was more notable in trained and
memory aroused rats. This suggested that the total number of nbM neurons and/or
the sensitivity of nbM neurons to experimental manipulations, especially learning
and memory performance, might reduce during aging.
PMID- 11011018
TI - Cellular determinants of reduced adaptability of the aging brain:
neurotransmitter utilization and cell signaling responses after MDMA lesions.
AB - Senescence is accompanied by the loss of neurons and synapses, and the
maintenance of function depends on adaptive change at the levels of synaptic
activity and cellular responsiveness. In the current study, we administered the
neurotoxin MDMA, to young and aged mice and assessed the effects on indices of
neuronal activity and cell signaling mediated through adenylyl cyclase. Young
mice given MDMA showed 80% depletion of dopamine in the caudate and 30% depletion
in the cerebral cortex; measurements of dopamine turnover indicated a
compensatory upregulation of the activity of the remaining neurons in the caudate
but downregulation in the cerebral cortex. Serotonin levels were comparatively
less affected but serotonin turnover was decreased significantly in both regions.
At the level of cell signaling, the young mice showed heterologous upregulation
of adenylyl cyclase activity and a consequent enhancement of responses mediated
through neurotransmitter receptors. In aged mice, MDMA treatment produced the
same degree of lesioning but substantially different changes in neuronal activity
and cell signaling. In the cerebral cortex, dopamine turnover was increased, and
serotonin turnover decreased, effects opposite in direction to those seen in
young mice. In the aged group, MDMA elicited heterologous loss of adenylyl
cyclase responses instead of displaying the supersensitivity that had been seen
in the young group. The aging brain thus displays maladaptation to the loss of
monoaminergic input, effects that may augment the functional impairment
associated with neurodegenerative disorders or stroke.
PMID- 11011019
TI - Androgen receptor-immunoreactivity in the forebrain of the Eastern Fence lizard
(Sceloporus undulatus).
AB - Androgen receptor (AR) distribution in the lizard forebrain and optic tectum was
examined using PG21 immunohistochemistry. In the male Eastern Fence lizard, AR
immunoreactive (-ir) nuclei were observed in the medial preoptic area,
ventromedial and arcuate hypothalamic nuclei, periventricular hypothalamus,
premammillary nucleus, bed nucleus of the stria terminalis, and ventral posterior
amygdala. Punctate immunostaining of neuronal processes (axons and/or dendrites)
was concentrated in the cortex, hypothalamus, and optic tectum. AR-ir nuclei in
the female brain were confined to the ventral posterior amygdala and ventromedial
hypothalamic nucleus. The AR distribution in the lizard brain is similar to that
reported for other vertebrate classes. Sex differences in AR-immunoreactivity may
contribute to sex-specific behaviors in the Eastern Fence lizard.
PMID- 11011020
TI - Motor neuron cell death in a mouse model of FALS is not mediated by the p53 cell
survival regulator.
AB - Mutant Cu/Zn superoxide dismutase (SOD1) associated with familial amyotrophic
lateral sclerosis (FALS) causes selective motor neuron loss through unknown
mechanisms of cell damage. Damaged neurons frequently undergo apoptosis mediated
by the p53 cell survival regulator. We therefore studied whether motor neuron
disease (MND) in mice expressing the human SOD1 mutant G93A is dependent on p53
by crossing G93A mice with p53-knockout mice. Since p53-/- mice's life expectance
is usually shorter (160+/-49 days, n=11) than the time at which the G93A mice die
from MND (212+/-50 days, n=7), only a few of the G93A/p53-/- double transgenics
were expected to live to experience MND. Nevertheless, four of the 22 G93A/p53-/-
mice succumbed to MND after 160+/-28 days, as expected under these conditions of
competing death risks if the absence of p53 fails to protect from MND. Thus, MND
in mice expressing G93A does not require p53. This conclusion is supported by
histology: pre-symptomatic G93A mice display disease-associated vacuoles within
the dendrites of motor neurons regardless of p53 status.
PMID- 11011021
TI - The spinal 5-HT system contributes to the generation of fictive locomotion in
lamprey.
AB - Activation of NMDA receptors evokes sustained fictive locomotion in the isolated
spinal cord of the sea lamprey Petromyzon marinus (P. marinus), but in the river
lamprey Lampetra fluviatilis (L. fluviatilis) the ventral root activity is often
irregular. A previous study showed that the number of 5-HT immunoreactive fibres,
neurones and varicosities are much lower in the spinal cord of L. fluviatilis
than in P. marinus. To further analyse the underlying mechanisms, the present
study investigated the role of the 5-HT system in stabilising fictive locomotion.
In P. marinus a blockade of 5-HT1A receptors by spiperone reversibly increased
the frequency and the coefficient of variation. This implies that there is an
endogenous release of 5-HT during fictive locomotion that is important for the
generation of locomotor activity. In L. fluviatilis bath applied NMDA or D
glutamate evoked in most cases irregular activity. An addition of 5-HT (0.5-2
microM) rapidly stabilised the burst generation and led to a sustained fictive
locomotion. In a split-bath configuration, NMDA administered to the rostral part
of the spinal cord in P. marinus evoked fictive locomotion in both the rostral
part and the first few segments of the caudal part. When spiperone was added to
the caudal part, the burst activity changed into tonic activity within 10 min.
Taken together, these results indicate that activity in the intrinsic 5-HT system
in the lamprey spinal locomotor network contributes significantly to the rhythm
generation. The quantitative differences with regard to the 5-HT plexus between
P. marinus and L. fluviatilis may account for the observed discrepancy between
the two species.
PMID- 11011022
TI - An in-vivo magnetic resonance imaging study of the olfactory bulbectomized rat
model of depression.
AB - The olfactory bulbectomized (OB) rat is a well-accepted animal model of
depression. The present magnetic resonance imaging (MRI) investigation
demonstrates alterations in signal intensities in cortical, hippocampal, caudate
and amygdaloid regions in OB animals, but not in sham operated controls.
Ventricular enlargement was also evident in OB animals. These alterations have
implications with regard to the face and construct validity of this model.
PMID- 11011023
TI - Retention of spatial information in hippocampally damaged rats overtrained on a
cartographic task.
AB - Hippocampal rats were overtrained on a cartographic task until they reached a
performance equal to that of the control group. Twenty-four days later, during a
retraining period, lesioned rats showed a profound retention deficit as compared
to controls. However, Expt. 2 shows no retention deficit when a guidance strategy
is used to acquire the spatial task. These results suggest that the hippocampus
is crucial for long-term retention/consolidation of allocentric spatial
information.
PMID- 11011024
TI - Laterality, somatotopy and reproducibility of the basal ganglia and motor cortex
during motor tasks.
AB - We investigated the basal ganglia, motor cortex area 4, and supplementary motor
area (SMA) using functional magnetic resonance imaging (fMRI) and five motor
tasks: switching between finger and toe movements, writing, finger tapping,
pronation/supination, and saccadic eye movements. We found reliable activation in
the caudate nucleus and putamen in single subjects without the need for inter
subject averaging. Percent signal changes in basal ganglia were smaller by a
factor of three than those in SMA or motor cortex (1% vs. 2.5-3%). There was a
definite foot-dorsal, hand-ventral basal ganglia somatotopy, similar to prior
data from primates. Saccadic eye movements activated the caudate nucleus
significantly more than the other tasks did. Unilateral movements produced
bilateral activation in the striatum even when motor cortex activation was
unilateral. Surprisingly, bilateral performance of the tasks led, on average, to
consistently smaller basal ganglia activation than did unilateral performance
(P<0.001), suggesting less inhibition of contralateral movements during bilateral
tasks. Moreover, there was a striking dominance pattern in basal ganglia motor
activation: the left basal ganglia were more active than the right for right
handers, regardless of the hand used. This lateralization appears much stronger
than that previously reported for motor cortex. Comparisons of inter-subject and
intra-subject reproducibility indicated a much larger variability in basal
ganglia and SMA compared to motor cortex, in spite of similar percent signal
changes in the latter two structures.
PMID- 11011025
TI - Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced
mechanical allodynia in the rat: possible immune modulation in neuropathic pain.
AB - Interleukin-6 (IL-6) is a pleiotrophic cytokine with a diverse range of actions
including the modulation of the peripheral and central nervous system. We have
previously shown significant IL-6 protein and messenger RNA elevation in rat
spinal cord following peripheral nerve injury that results in pain behaviors
suggestive of neuropathic pain. These spinal IL-6 levels correlated directly with
the mechanical allodynia intensity following nerve injury. In the current study,
we sought to determine whether it is possible to attenuate mechanical allodynia
and/or alter spinal glial activation resulting from peripheral nerve injury by
specific manipulation of IL-6 with neutralizing antibodies or by global immune
modulation utilizing immunogamma-globulin (IgG). Effects of peripheral
administration of normal goat IgG and intrathecal (i.t.) administration of IL-6
neutralizing antibody, normal goat or normal rat IgG on mechanical allodynia
associated with L5 spinal nerve transection were compared. Spinal glial
activation was assessed at day 10 post surgery by immunohistochemistry. Low dose
(0.01-0.001 microg) goat anti-rat IL-6 i.t. administration (P=0.025)
significantly decreased allodynia and trended towards significance at the higher
dose (0.08 microg to 0.008 microg, P=0.062). Low doses (0.01-0.001 microg) i.t.
normal goat and rat IgG significantly attenuated mechanical allodynia, but not at
higher doses (0.08-0.008 microg; P=0.001 for both goat and rat IgG). Peripherally
administered normal goat IgG (30 or 100 mg/kg) did not attenuate mechanical
allodynia. Spinal glial activation was unaltered by any treatment. These data
provide further evidence for the role of central IL-6 and neuroimmune modulation
in the etiology of mechanical allodynia following peripheral nerve injury.
PMID- 11011026
TI - Differential effects of stimulants on monoaminergic transporters: pharmacological
consequences and implications for neurotoxicity.
AB - Many psychostimulants alter plasmalemmal monoaminergic transporter function.
Some, such as cocaine, prevent the reuptake of newly released dopamine, serotonin
or norepinephrine into their associated neurons. Others, such as the
amphetamines, facilitate release of these transmitters into the extraneuronal
space by causing a reversal of function of these carrier proteins. An
understanding of how psychostimulants regulate the function of not only
plasmalemmal, but also vesicular monoamine transporter function is important to
appreciate the pharmacological and sometimes neurotoxic consequences of
administering these drugs, as well as the physiological regulation of these
carrier proteins. Hence, this review will describe recent ex vivo studies
investigating the rapid and differential affects of several stimulants on both
plasmalemmal and vesicular monoamine transporter function.
PMID- 11011027
TI - Nitric oxide donors and angiotensin-converting enzyme inhibitors act in concert
to inhibit human angiotensin-converting enzyme activity and platelet aggregation
in vitro.
AB - This study investigates the effects of exogenous and endogenous nitric oxide (NO)
on human circulating and endothelial angiotensin-converting enzyme activity and
platelet aggregation. The NO donor S-nitroso-N-acetylpenicillamine (10(-8)-10(-6)
M) significantly and dose-dependently inhibited serum angiotensin-converting
enzyme activity. The concomitant addition of S-nitroso-N-acetylpenicillamine to
angiotensin-converting enzyme inhibitor-treated (captopril or enalaprilat) serum,
further reduced angiotensin-converting enzyme activity. In cultured endothelial
cells from human umbilical veins (HUVECs), both S-nitroso-N-acetylpenicillamine
and 3-morpholinosydnonimine (SIN-1) significantly reduced angiotensin-converting
enzyme activity. An additative effect was seen with a combined treatment of
captopril and S-nitroso-N-acetylpenicillamine. Treatment with the NO synthase
inhibitor N(G)-monomethyl-L-arginine (L-NMMA) did not affect angiotensin
converting enzyme activity. Thrombin inhibited endothelial angiotensin-converting
enzyme activity, an effect that was abolished when cells were pretreated with L
NMMA. Adenosine 5'-diphosphate (ADP)-induced platelet aggregation was inhibited
with S-nitroso-N-acetylpenicillamine, SIN-1 and nitroglycerine. Captopril did not
affect aggregation, while a high concentration of enalaprilat (10(-4) M) reduced
it. The concomitant addition of 10(-5) M angiotensin-converting enzyme inhibitor
to NO donor-treated platelets resulted in a further reduction of platelet
aggregation. This effect was most evident with SIN-1 and enalaprilat. In
conclusion, both exogenous and endogenous NO inhibit human angiotensin-converting
enzyme activity. NO donors and angiotensin-converting enzyme inhibitors act in
concert to inhibit angiotensin-converting enzyme and platelet aggregation.
PMID- 11011028
TI - The chemotherapeutic oxaliplatin alters voltage-gated Na(+) channel kinetics on
rat sensory neurons.
AB - The chemotherapeutic oxaliplatin causes a sensory-motor neuropathy with
predominantly hyperpathic symptoms. The mechanism underlying this
hyperexcitability was investigated using rat sensory nerve preparations, dorsal
root ganglia and hippocampal neurons. Oxaliplatin resulted in an increase of the
amplitude and duration of compound action potentials. It lengthened the
refractory period of peripheral nerves suggesting an interaction with voltage
gated Na(+) channels. Application of oxaliplatin to dorsal root ganglion neurons
resulted in an increase of the Na(+) current, a block of the maximal amplitude
and a shift of the voltage-response relationship towards more negative membrane
potentials. The effect was detectable on 13 of 18 tested cells. This observation,
together with the absence of any effect on Na(+) currents of hippocampal neurons,
suggests that the interaction of oxaliplatin is restricted to one or more channel
subtypes. The effect of oxaliplatin could be antagonised by the Na(+) channel
blocker carbamazepine which could be used to reduce side effects of oxaliplatin
therapy in patients.
PMID- 11011029
TI - BRL37344, but not CGP12177, stimulates fuel oxidation by soleus muscle in vitro.
AB - The beta(3)-adrenoceptor agonist, (RR+SS)-(+/-)-4-[2-)2-)3-chlorophenyl)-2
hydroxyethyl)amino)propyl]ph enoxyacetate (BRL37344), stimulated fuel utilisation
by isolated mouse soleus muscle at concentrations 10- to 100-fold lower than
those required to stimulate lipolysis in brown adipocytes. At 1x10(-10) M
BRL37344, uptake and phosphorylation of 2-deoxyglucose was increased (40%), as
was glucose-oxidation (50%), palmitate-oxidation (70%) and oxidation of [2
14C]pyruvate (2-fold), indicating stimulation of tricarboxylic acid cycle
reactions. Oxidation of [1-14C]pyruvate was unaffected, indicating no stimulation
of pyruvate dehydrogenase activity. Other beta(3)-adrenoceptor agonists,
disodium(RR)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]- 1,3
benzodioxazole-2,2-dicarboxylate (CL316,243, 1x10(-7) M) and (S)-4-?2-[2-hydroxy
3-(4-hydroxyphenoxy)propylamino]ethyl?pheno xymeth ylcyclohexylphosphiric acid
lithium salt (SB226552, 1x10(-9) M), achieved similar stimulation of 2
deoxyglucose uptake and phosphorylation but (+/-)-4-(3-t-butylamino-2
hydroxypropoxy)benzimidazol-2-one (CGP12177A) had no effect. The inhibitor of
protein kinase A, H-89 (isoquinolinesulfonamide), had little effect on the
stimulation of pyruvate-oxidation by BRL37344, while the specific inhibitor of
protein kinase C, bisindolylmaleimide IX, reduced the stimulated rate to slightly
below basal values. We consider that these responses provide evidence of the
presence of a novel beta-adrenoceptor in skeletal muscle, which we have termed
beta(skel)-adrenoceptor.
PMID- 11011030
TI - A new structural class of subtype-selective inhibitor of cloned excitatory amino
acid transporter, EAAT2.
AB - We have studied the pharmacological effects of (RS)-2-amino-3-(3-hydroxy-5
methylisoxazol-4-yl)propionic acid (AMPA) and the enantiomers of (RS)-2-amino-3
(3-hydroxy-1,2, 5-thiadiazol-4-yl)propionic acid (TDPA) on cloned human
excitatory amino acid transporter subtypes 1, 2 and 3 (EAAT1-3) expressed in Cos
7 cells. Whereas AMPA and (R)-TDPA were both inactive as inhibitors of [3H]-(R)
aspartic acid uptake on all three EAAT subtypes, (S)-TDPA was shown to
selectively inhibit uptake by EAAT2 with a potency equal to that of the
endogenous ligand (S)-glutamic acid. (S)-TDPA thus represents a new structural
class of EAAT2 inhibitor that will serve as a lead for the design of EAAT
selective inhibitors.
PMID- 11011031
TI - Effect of anti-inflammatory bowel disease drug, E3040, on urate transport in rat
renal brush border membrane vesicles.
AB - To confirm the assumption that 6-hydroxy-5, 7-dimethyl-2-methylamino-4-(3
pyridylmethyl)benzothiazole (E3040) acts on urate reabsorption by inhibiting
urate-anion exchange at the luminal membrane of renal tubules, we investigated
the inhibitory effect of E3040 and its two conjugated metabolites on hydroxyl ion
(OH(-)) gradient-dependent urate uptake into brush border membrane vesicles from
rat renal cortex and compared it with other uricosuric agents. The order of
potency was AA193 (5-chloro-7, 8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7
carboxylic acid)>benzbromarone>E3040>probenecid>E3040 sulfate>E3040 glucuronide.
Furthermore, kinetic analysis revealed that E3040 may be a competitive inhibitor
of the OH(-) gradient-dependent uptake of urate into brush border membrane
vesicles.
PMID- 11011032
TI - Inhibitors of tyrosine phosphatases block angiotensin II inhibition of Na(+)
pump.
AB - To determine how angiotensin II inhibits the Na(+) pump (Na(+), K(+)-ATPase) in
rat zona glomerulosa, we selectively blocked signaling proteins that could be
activated by the angiotensin AT(1) receptor and known to affect Na(+) pump
activity. Inhibitors of protein kinase C [calphostin C (1 microM); staurosporine
(1 microM)], phospholipase A(2) [arachidonyl triflouromethyl ketone (25 microM);
quinacrine (75 microM)], diacylgycerol lipase [RHC-80267 (5 microM)], and
tyrosine phosphorylation [tyrphostin 47 (100 microM)] had no effect on
angiotensin II inhibition of the Na(+) pump. On the other hand, inhibitors of
tyrosine phosphatases [phenylarsine oxide (5 microM) and 4-bromotetramisole
oxalate (100 microM)] blocked angiotensin II inhibition, where as inhibitors of
serine/threonine phosphatases [okadaic acid (1 microM) and microcystin (1.5
microM)] did not. Thus, angiotensin II inhibition of the Na(+) pump may in part
be mediated by a tyrosine phosphatase.
PMID- 11011033
TI - Effects of dopaminergic agents on carrageenan hyperalgesia in rats.
AB - The present study explored the role of central dopaminergic transmission in a
model of carrageenan-induced inflammatory pain by examining the effects of
selective agonists and antagonists of dopamine receptors. The results were as
follow: (1) LY171555 (trans-(-)-4aR-4,4a,5,6,7,8,8a,9-Octahydro-5-propyl-1H
pyrazolo[3, 4-g]quinoline hydrochloride), dopamine D(2) receptor agonist,
produced anti-hyperalgesia or hypoalgesia in the inflamed hindpaws and non
inflamed hindpaws, respectively; spiperone hydrochloride (8-[4-(4-Fluorophenyl)-4
oxobutyl]-1-phenyl-1,3,8-triazaspiro[4, 5]decan-4-one hydrochloride), dopamine
D(2) receptor antagonist, decreased the pain threshold of the non-inflamed
hindpaws. (2) (+/-)-SKF38393 hydrochloride ((+/-)-1-Phenyl-2,3,4, 5-tetrahydro
(1H)-3-benzazepine-7,8-diol hydrochloride), dopamine D(1) receptor agonist,
produced anti-hyperalgesia or hypoalgesia when administered in a high dose (600
nmol), and decreased the pain threshold of non-inflamed hindpaws when
administered in a low dose (150 nmol); R(+)-SCH23390 hydrochloride (R(+)-7-Chloro
8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine hydrochloride),
dopamine D(1) receptor antagonist, induced anti-hyperalgesia or hypoalgesia,
respectively. The present study suggests that the dopaminergic system is involved
in the central modulation of inflammatory hyperalgesia, and that the different
effects are probably induced by the different receptors.
PMID- 11011034
TI - Effects of flurbiprofen and its enantiomers on the spinal c-Fos protein
expression induced by noxious heat stimuli in the anaesthetized rat.
AB - We have evaluated the effects of either intravenous or intraplantar
administration of racemic-, S(+)- and R(-)-flurbiprofen on the spinal c-Fos
protein expression after a single noxious heat stimulation (52 degrees C for 15
s) of the rat hindpaw in urethane anaesthetized rats. Two hours after noxious
heat, numerous c-Fos protein immunoreactive (c-Fos-IR) nuclei (>70 c-Fos-IR
nuclei per section at the level of L4-L5 segments) were observed with essential
localization in the superficial (I-II) laminae of the spinal dorsal horn, i.e.
areas containing numerous neurons driven exclusively by noxious stimuli.
Considering the number of c-Fos-IR nuclei in laminae I-II, the intravenous
injection of racemic-flurbiprofen (0.3, 3 and 9 mg/kg) was inefficacious and S(+)
flurbiprofen had weak and non-dose-related effects. The same doses of R(-)
flurbiprofen produced dose-related effects (r=0.58, P<0.05) with weak, but
significant, effects for doses of 3 and 9 mg/kg (18+/-6% and 26+/-5% reduction of
the number of noxious heat-evoked c-Fos-IR nuclei in laminae I-II, P<0.05 and
P<0.01, respectively). The weak effects of R(-)-flurbiprofen are probably due to
the central site of action since the intraplantar injection of a relatively high
dose of 30 microg is inefficacious. These results provide further evidence for
weak effects of non-steroidal anti-inflammatory drugs and their enantiomers on
the acute responses to nociceptive stimulus which are very efficacious upon
inflammatory nociception, but not upon brief noxious heat-evoked nociception.
PMID- 11011035
TI - Role of endogenous endothelins in catecholamine secretion in the rat adrenal
gland.
AB - We investigated the role of endogenous endothelins in catecholamine secretion in
response to transmural electrical stimulation in the retrogradely perfused rat
adrenal gland. (R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-++
+methy l-pentanoyl]amino-3-[3-(1-methyl-1H-indoyl)]propionyl]amino-3-(2-+
++pyridyl) propionic acid (FR139317; 0.03-3 microM), an endothelin ET(A) receptor
antagonist, inhibited the electrical stimulation-induced epinephrine and
norepinephrine output. Neither N-cis-2, 6-dimethylpiperidinocarbonyl-L-gamma
methylleucyl-D-1- methoxycarbonyl tryptophanyl-D-norleucine (BQ-788; 0.03-3
microM), an endothelin ET(B) receptor antagonist, nor phosphoramidon (1-100 mM),
an endothelin-converting enzyme inhibitor, affected the catecholamine output
responses. However, the inhibition by FR139317 of the catecholamine output
responses was abolished by pretreatment with phosphoramidon (100 mM) or BQ-788 (3
microM). These results indicate that activation of endothelin ET(B) receptors by
endogenous endothelins inhibits the catecholamine output responses under the
condition in which endothelin ET(A) receptors are blocked. Exogenous endothelin-1
(1-100 nM) did not affect the catecholamine output responses, but it inhibited
the responses under treatment with phosphoramidon and FR139317. Activation of
endothelin ET(A) receptors may interfere with the endothelin ET(B) receptor
mediated inhibitory action on the neuronally evoked secretion of adrenal
catecholamines.
PMID- 11011036
TI - The cyclo-oxygenase inhibitor nimesulide induces conditioned place preference in
rats.
AB - Two cyclo-oxygenase inhibitors, indomethacin and nimesulide, have been shown to
potentiate morphine-induced stimulation of meso-accumbens dopamine neurons. In
this study, an unbiased conditioned place preference procedure was used to
evaluate whether nimesulide produces motivational effect after systemic
administration in rats. These results show that nimesulide, at doses 0.1, 0.5 and
1 mg/kg, even lower than those usually applied for inflammatory conditions,
induces conditioned place preference in rats, suggesting that it might possess
rewarding properties in humans.
PMID- 11011037
TI - Guanylate cyclase and not ATP-dependent K(+) channels seems temperature-dependent
in smooth muscle relaxation of human umbilical arteries.
AB - The effects of K(+) channel opener, nicorandil [N-(2-hydroxyethyl)-nicotinamide
nitrate], on isolated human umbilical arteries were investigated at two
temperatures: 37 degrees C and 25 degrees C. The purpose of this investigation
was: (1) to confirm the relaxant effect of nicorandil, (2) to elucidate the
influence of endothelium and temperature on nicorandil-induced relaxation, (3) to
determine which of guanylate cyclase or ATP-sensitive K(+) channels was
implicated in temperature-induced relaxation of smooth muscles. Rings, 3-mm-wide,
were suspended in organ chambers for isometric force measurement. All solutions
were aerated with 95% O(2)-5% CO(2) and maintained at 37 degrees C or 25 degrees
C (cooling), pH 7.4. The presence of an intact endothelium was confirmed by
immunohistochemistry. During the first set of experiments after contraction with
5-hydroxytryptamine (5-HT 10(-5) M), nicorandil (10(-9)-10(-4) M) was added to
the organ chambers with controls and in with rings incubated with L-arginine, N
nitro-L-arginine (L-NNA) an inhibitor of nitric oxide (NO) synthase, [1-H-(1,2,4)
oxadiazole (4,3-a) quinoxalin-1-one] (ODQ), a specific inhibitor of guanylate
cyclase, or glibenclamide, an antagonist of nicorandil, all at 10(-5) M. In
another set of experiments, rings were contracted with 5-HT (10(-5) M) and
relaxed with 3-morpholinosydnonimine [SIN-1 (10(-9)-3x10(-5) M) or cromakalim
(10(-9)-3x10(-5) M)]. Our results showed that nicorandil induced concentration
dependent relaxation. At 37 degrees C, in the control, the maximum relaxation was
90+/-5%, and 60+/-8% at 25 degrees C (P<0.01). However, the relaxation at 37
degrees C or 25 degrees C remained unchanged after pretreatment with L-arginine,
L-NNA, this suggests that the same concentration of drugs used in this type of
vessel does not appear to modulate the relaxant effect of nicorandil. On the
other hand, we observed that the relaxant effect of SIN-1 was 72+/-5% at 37
degrees C and only 28+/-7% at 25 degrees C (P<0.01). However, relaxations with
cromakalim were partly influenced by cooling. In the presence of ODQ, the
nicorandil-induced relaxation observed at 37 degrees C or 25 degrees C was less
than that in the control and in the rings incubated with glibenclamide. These
results for human umbilical arteries indicate that cooling decreases the
relaxation response of smooth muscles and that this is partly due to a decreased
response to guanylate cyclase.
PMID- 11011039
TI - Hemodynamic effects of MF 10058, a new cardioselective muscarinic M(2) receptor
antagonist, in conscious dogs.
AB - The 5-?4-[4-(diethylamino)butyl]-1-piperidinyl?acetyl-5H-dibenz[b, f]-azepine (MF
10058) is a new potent and selective muscarinic M(2) receptor antagonist. The
hemodynamic effects of MF 10058 were investigated in conscious freely moving
dogs. Placebo and three doses of MF 10058 (2, 4 and 8 mg/kg) were orally
administered according to a randomised four-way crossover design. Heart rate,
cardiac conduction times, systolic and diastolic blood pressure were
telemetrically recorded for 12-24 h after dosing. After placebo administration, a
consistent reduction over time in heart rate was observed during the night-time
period (-15%, P=0.019). MF 10058 administration antagonised the nocturnal
bradycardia and shortened QT interval. The effect of the drug reached
statistically significance, compared to placebo, with the highest dose of 8 mg/kg
(+19% on heart rate, P=0.013; -4% on QT interval, P=0.049). The effect on heart
rate lasted for the entire 24-h observation period (+16%, P=0.030). Nocturnal
systolic and diastolic blood pressure were not significantly affected by MF
10058. No other signs of peripheral or central cholinergic block were observed at
any dose. The results of this study demonstrated that oral administration of MF
10058 produces long-lasting hemodynamic effects in the conscious dog. The drug
has a therapeutic potential for the treatment of bradycardic disorders.
PMID- 11011038
TI - Possible mechanism of cardioprotective effect of angiotensin preconditioning in
isolated rat heart.
AB - The present study is designed to investigate the mechanism of cardioprotective
effect of angiotensin II preconditioning. Isolated perfused rat heart was
subjected to global ischaemia for 30 min followed by reperfusion for 120 min.
Coronary effluent was analysed for lactate dehydrogenase and creatine kinase
enzyme release to assess the degree of cardiac injury. Myocardial infarct size
was estimated macroscopically using triphenyltetrazolium chloride staining. Four
episodes of angiotensin II preconditioning markedly reduced lactate dehydrogenase
and creatine kinase release in the coronary effluent and decreased myocardial
infarct size. Administration of prazosin (alpha(1)-adrenoceptor antagonist)
before global ischaemia reduced the extent of ischaemia-reperfusion-induced
myocardial injury. Moreover, administration of prazosin during angiotensin II
preconditioning or depletion of biogenic amines by reserpinisation (0.5 mg/kg
i.p.) did not affect the cardioprotective effect of angiotensin II
preconditioning. On the other hand, colchicine (5 mg/kg i.p.) or polymyxin B (50
microM) treatment markedly attenuated the cardioprotective effect of angiotensin
II preconditioning. On the basis of these results, it may be concluded that the
cardioprotective effects of angiotensin II preconditioning may be mediated
through protein kinase C and may not involve release of norepinephrine or
activation of alpha(1)-adrenoceptor.
PMID- 11011040
TI - Effect of a decrease in pH on responses mediated by P2 receptors in the rat
mesenteric arterial bed.
AB - The present study investigated the effect of acidosis (reduction in pH of the
Krebs' solution from 7.4 to 6.9) on responses to vasoconstrictors and
vasodilators, with a focus on purines, in the rat isolated perfused mesenteric
arterial bed. alpha,beta-Methylene ATP (alpha,beta-meATP) (10 microM), a
selective P2X receptor agonist, elicited a desensitizing vasocontraction, which
was not significantly affected by a reduction in pH to 6.9. Contractions to ATP
were also not significantly different at pH 6.9 compared to pH 7.4. In contrast,
contractile responses to noradrenaline, methoxamine, and vasopressin were greatly
attenuated at pH 6.9 (by 48-83%; P<0.01). At raised tone, vasorelaxations to ADP
at P2Y receptors, and to calcitonin gene-related peptide (CGRP), were not
different at pH 7.4 and pH 6.9. These data indicate that a reduction in pH (to
6.9) differentially affects responses to vasoconstrictors in the rat mesenteric
arterial bed. There is no effect on contractions mediated via P2X receptors, but
contractions to noradrenaline, methoxamine and vasopressin are greatly
attenuated.
PMID- 11011041
TI - Comparison of bisoprolol and carvedilol cardioprotection in a rabbit ischemia and
reperfusion model.
AB - Carvedilol, a selective alpha(1) and non-selective beta-adrenoceptor antagonist
and antioxidant, has been shown to provide significant cardiac protection in
animal models of myocardial ischemia. To further explore the mechanisms
contributing to the efficacy of carvedilol cardioprotection, the effects of
carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity
(an index of neutrophil accumulation) were compared with a beta(1) selective
adrenoceptor antagonist, bisoprolol. Carvedilol (1 mg/kg) or bisoprolol (1 mg/kg)
was given intravenously 5 min before reperfusion. In vehicle-treated rabbits,
ischemia (45 min) and reperfusion (240 min) resulted in significant increases in
left ventricular end diastolic pressure, large myocardial infarction (64.7+/-2.6%
of area-at-risk) and a marked increase in myeloperoxidase activity (64+/-14 U/g
protein in area-at-risk). Carvedilol treatment resulted in sustained reduction of
the pressure-rate-index and significantly smaller infarcts (30+/-2.9, P<0.01 vs.
vehicle) as well as decreased myeloperoxidase activity (26+/-11 U/g protein in
area-at-risk, P<0.01 vs. vehicle). Administration of bisoprolol at 1 mg/kg
resulted in a pressure-rate-index comparable to that of carvedilol and also
decreased infarct size (48.4+/-2.5%, P<0.001 vs. vehicle, P<0.05 vs. carvedilol),
although to a significantly lesser extent than that observed with carvedilol.
Treatment with bisoprolol failed to reduce myeloperoxidase activity in the
ischemic myocardial tissue. In addition, carvedilol, but not bisoprolol, markedly
decreased cardiac membrane lipid peroxidation measured by thiobarbituric acid
formation. Taken together, this study suggests that the superior cardioprotection
of carvedilol over bisoprolol is possibly the result of carvedilol's antioxidant
and anti-neutrophil effects, not its hemodynamic properties.
PMID- 11011042
TI - Cytokine enhancement of endothelin ET(B) receptor-mediated contraction in human
temporal artery.
AB - Segments of human temporal artery were incubated in organ culture for 2 days in
the absence or presence of cytokines. Thereafter, contractions were induced by
the selective endothelin ET(B) receptor agonist sarafotoxin S6c, a peptide that
does not induce contraction in fresh human temporal artery. Interleukin-1beta was
most potent in increasing the sarafotoxin-induced contraction in cultured
segments. Tumour necrosis factor (TNF)-alpha increased the magnitude of
contraction to a similar degree, but at a higher dose. A significant increase was
also induced by interferon-gamma, but not by interleukin-6 at the concentrations
used. The results suggest that endothelin ET(B) receptor-mediated contraction can
be enhanced by pro-inflammatory cytokines in a concentration-dependent manner,
and this may have relevance for pathophysiological conditions where inflammation
and vasoactivity are important.
PMID- 11011043
TI - Myocardial contractility after infarction and carnitine palmitoyltransferase I
inhibition in rats.
AB - Inhibition of carnitine palmitoyltransferase I with etomoxir increases
sarcoplasmic reticulum Ca(2+)-transport and V(1) isomyosin expression. To test
whether etomoxir attenuates contractile dysfunction after myocardial infarction,
we compared the contractility of papillary muscles from etomoxir- and placebo
treated rats 6 weeks after infarction. Etomoxir induced cardiac hypertrophy in
animals with small infarctions, and enhanced compensatory heart growth at large
infarct size. Contractile function of papillary muscles from etomoxir-treated
rats was improved particularly in animals with small infarctions. Thus, induction
of mild cardiac hypertrophy by etomoxir in rats with small infarctions may be
beneficial for myocardial performance.
PMID- 11011044
TI - Tempol, a membrane-permeable radical scavenger, reduces dinitrobenzene sulfonic
acid-induced colitis.
AB - Inflammatory bowel disease is characterized by oxidative and nitrosative stress,
leukocyte infiltration, and up-regulation of intercellular adhesion molecule 1
(ICAM-1) expression in the colon. The aim of the present study was to examine the
effects of tempol, a membrane-permeable radical scavenger, in rats subjected to
experimental colitis. Colitis was induced in rats by intracolonic instillation of
dinitrobenzene sulfonic acid. Rats experienced bloody diarrhea and significant
loss of body weight. At 4 days after the administration of dinitrobenzene
sulfonic acid, the colon injury comprised of large areas of mucosal necrosis.
Neutrophil infiltration (measured as increase in myeloperoxidase activity in the
mucosa) was associated with up-regulation of ICAM-1 and expression of P-selectin
and high levels of malondialdehyde (an indicator of lipid peroxidation).
Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) synthetase showed an
intense staining in the inflamed colon. Treatment of rats with tempol (15 mg/kg
daily i.p.) significantly reduced the appearance of diarrhea and the loss in body
weight. This was associated with a remarkable amelioration of the disruption of
the colonic architecture as well as a significant reduction in the degree of both
neutrophil infiltration and lipid peroxidation in the inflamed colon. Tempol also
reduced the appearance of nitrotyrosine and poly (ADP-ribose) synthetase
immunoreactivity in the colon as well as the up-regulation of ICAM-1 and P
selectin. The results of this study suggest that membrane-permeable radical
scavengers, such as tempol, exert beneficial effects in experimental colitis and
may, hence, be useful in the treatment of inflammatory bowel disease.
PMID- 11011045
TI - Effect of a novel bifunctional endothelin receptor antagonist, IRL 3630A, on
guinea pig respiratory mechanics.
AB - This study characterized the in vitro pharmacological properties of a newly
developed endothelin receptor antagonist, N-butanesulfonyl-[N-(3, 5
dimethylbenzoyl)-N-methyl-3-[4-(5-isoxazolyl)-phenyl]-(D)- alanyl]-( L)
valineamide sodium salt (IRL 3630A), and its in vivo effects on respiratory
mechanics were determined. IRL 3630A showed highly balanced affinities to human
endothelin ET(A) and ET(B) receptors, giving apparent K(i) values of 1.5 and 1.2
nM, respectively. This compound also potently antagonized the endothelin-1
induced intracellular Ca(2+) increases in both embryonic bovine tracheal (EBTr)
cells expressing endothelin ET(A) receptors and human Girardi heart (hGH) cells
expressing endothelin ET(B) receptors. In guinea pig isolated tracheas having
both endothelin ET(A) and ET(B) receptors, IRL 3630A greatly inhibited endothelin
1-induced contraction (pA(2)=7.1), which was partially or scarcely suppressed by
the endothelin ET(A) receptor antagonist cyclo[-(D)-Trp-(D)-Asp-(L)-Pro-(D)-Val
(L)-Leu-] (BQ-123) or the endothelin ET(B) receptor antagonist N-(3, 5
dimethylbenzoyl)-N-methyl-3-(4-phenyl)-(D)-phenylalanyl-(L)-t ryptop han (IRL
2500), respectively. Bolus i.v. injections of IRL 3630A administered into
anaesthetized guinea pigs at 10 and 30 microg/kg inhibited endothelin-1 (1.3
microg/kg)-induced changes in respiratory resistance and compliance in a dose
dependent manner, whereas both sodium 2-benzo[1, 3]dioxol-5-yl-4-(4-methoxy
phenyl)-4-oxo-3-(3,4, 5-trimethoxy-benzyl)-but-2-enoate (an endothelin ET(A)
receptor antagonist: PD 156707) and IRL 2500 at doses of up to 30 microg/kg did
not affect endothelin-1-induced changes in respiratory mechanics, reflecting the
in vitro results. IRL 3630A is thus an effective bifunctional endothelin receptor
antagonist, and will be useful in clarifying the role of endothelin in pulmonary
diseases such as bronchial asthma.
PMID- 11011046
TI - Involvement of blockade of leukotriene B(4) action in anti-pruritic effects of
emedastine in mice.
AB - The anti-pruritic activity of emedastine difumarate was studied in mice.
Emedastine (0.03-0.3 mg/kg) inhibited scratching induced by intradermal injection
of histamine (100 nmol/site). Scratching induced by substance P (100 nmol/site)
and leukotriene B(4) (0.03 nmol/site), but not by serotonin (100 nmol/site), was
also suppressed by emedastine (0.03-0.3 mg/kg). Intradermal injection of
substance P increased the cutaneous concentration of leukotriene B(4), which was
not affected by emedastine. These results suggest that the inhibition by
emedastine of substance P-induced itch-associated response is mediated by the
blockade of leukotriene B(4) action. Anti-leukotriene B(4) action, as well as the
anti-histamine action, may contribute to the anti-pruritic effects of emedastine.
PMID- 11011047
TI - The 5-HT(2C/2B) receptor agonist, m-chlorophenylpiperazine, increases plasma
glucagon levels in rats.
AB - Effects of the 5-HT(2C/2B) receptor agonist m-chlorophenylpiperazine (mCPP) on
plasma glucagon levels were investigated in rats. mCPP dose dependently increased
plasma glucagon levels. Hyperglucagonemia elicited by mCPP was prevented by the 5
HT(2A/2B/2C) receptor antagonist, ritanserin, while the 5-HT(2A) receptor
antagonist, ketanserin, did not show any effect. Increases in glucagon levels
induced by mCPP were inhibited by prior adrenodemedullation. These results
indicate that increases in plasma glucagon levels induced by mCPP are mediated by
the 5-HT(2C/2B) receptor which in turn facilitates adrenaline release.
PMID- 11011048
TI - Serum leptin levels after central and systemic injection of a serotonin
precursor, 5-hydroxytryptophan, in mice.
AB - Effects of peripheral and central injections of a serotonin (5-hydroxytryptamine,
5-HT) precursor, 5-hydroxytryptophan (5-HTP), on serum leptin levels were studied
in mice. Intracerebroventricular (i.c.v.) injection of 5-HTP or 5-HT did not
increase serum leptin levels, although the peripheral injection of 5-HTP elicited
an apparent hyperleptinemia. The elevation of serum leptin levels in mice induced
by the peripheral injection of 5-HTP was inhibited by pretreatment with the
peripheral aromatic amino acid decarboxylase inhibitor, benserazide. Furthermore,
the peripheral injection of 5-HT increased serum leptin levels. These results
suggest that the hyperleptinemia following systemic injection of 5-HTP is
elicited by 5-HT formed in the peripheral system.
PMID- 11011050
TI - 2-Arachidonylglycerol, an endogenous cannabinoid, inhibits tumor necrosis factor
alpha production in murine macrophages, and in mice.
AB - 2-Arachidonylglycerol (2-AG) inhibits the production in vitro of tumor necrosis
factor-alpha (TNF-alpha) by mouse macrophages, as well as in mice. It has no
effect on the production of nitric oxide (NO). The effect on TNF-alpha is
enhanced when 2-AG is administered together with 2-linoleylglycerol (2-Lino-G)
and 2-palmitylglycerol (2-PalmG), an 'entourage effect' previously noted in
several behavioral and binding assays. 2-AG also suppresses the formation of
radical oxygen intermediates.
PMID- 11011049
TI - Inverse agonism by Dmt-Tic analogues and HS 378, a naltrindole analogue.
AB - The potent delta-opioid receptor antagonist H-2',6-L-tyrosine(Dmt)-1, 2,3,4
tetrahydroisoquinoline-3-carboxylic acid (Tic-OH) exhibited partial inverse
agonism (EC(50)=6.35 nM, E(max)=-18.87%) for [35S]GTPgammaS binding and H-Dmt-Tic
NH(2) was a neutral antagonist (no effect up to 30 microM). In contrast
N,N(CH(3))(2)-Dmt-Tic-NH(2) was a full inverse agonist (EC(50)=2.66 nM, E(max)=
35.95%) similar to ICI 174864 ([N,N-diallyl-Tyr(1),Aib(2,3),Leu(5)]enkephaline)
but with a 3.5-fold higher EC(50). In comparison, naltrindole was a neutral
antagonist while its analogue HS 378 was a partial inverse agonist (E(max)=
12.99%).
PMID- 11011051
TI - Transduction of the discriminative stimulus effects of zolpidem by GABA(A)/alpha1
receptors.
AB - Zolpidem is an imidazopyridine with high affinity at gamma-aminobutyric acid(A)
(GABA(A)) receptors expressing alpha1 subunits. In squirrel monkeys trained to
discriminate a high dose of zolpidem (> or =3.0 mg/kg) from saline, zolpidem and
another GABA(A)/alpha1 receptor-preferring agonist, zaleplon, substituted dose
dependently for zolpidem, whereas the non-selective agonists diazepam and
triazolam were did not substitute at any dose tested. These findings offer the
first evidence for a selective role of GABA(A)/alpha1 receptors in the
interoceptive effects of high doses of zolpidem.
PMID- 11011062
TI - Neuromagnetic integrated methods tracking human brain mechanisms of sensorimotor
areas 'plastic' reorganisation.
AB - The potential for reorganization in the adult brain has been largely
underestimated in the past and we are just beginning to understand the
organisational principles involved in functional recovery. A bulk of experimental
evidences have been accumulated in support of the hypothesis that neuronal
aggregates adjacent to a lesion in the cortical brain areas can be progressively
vicarious to the function of the damaged neurones. Such a reorganisation, if
occurring in the affected hemisphere of a patient with a monohemispheric lesion,
should significantly modify the interhemispheric symmetry of somatotopic
organisation of the sensorimotor cortices, both in terms of absolute surfaces and
number of "recruited" neurons, as well as of spatial coordinates. In fact, a
roughly symmetrical organisation of sensorimotor - particularly for the hand
contorl - in the right and left hemisphere has been observed in healthy humans by
different methods of functional brain imaging, including fMRI, TMS, MEG, HD-EEG.
Not uniform results about the functional brain activity related to sensory, motor
and cognitive functions in normal and diseased subjects are often due to
differences in the experimental paradigm designed as well as in the spatial and
temporal resolution of the neuroimaging techniques used. The multi-modal
integration of data obtained with several neuroimaging techniques allowed a
coherent modelling of human brain higher functions. Functional magnetic resonance
imaging (fMRI) provided fine spatial details (millimetres) of the brain
responses, which were compared with the cortical maps of the motor output to
different body districts obtained with transcranial magnetic stimulation (TMS).
Magnetoencephalography (MEG) ability to study sensorimotor areas by analysing
cortical magnetic fields, is also complementary to the motor cortex topographical
mapping provided by TMS. MEG high temporal resolution allows to detect relatively
restricted functional neuronal pools activated during cerebral processing of
external stimuli. Moreover, these brain responses can be investigated with
magnetoencephalography (MEG) and high density electroencephalography (EEG)
techniques, with elevated time resolution (ms). With respect to the high
resolution EEG technique, the MEG technique allowed a more precise localisation
of the sites of neural activity buried into the cortical sulci, but was unable to
detect the response of the crown of the cortical giri and of the frontal-mesial
cortex (including the supplementary motor area), because of its poor sensitivity
to radially oriented dipoles. The integration of functional and anatomical
information provide cues on the relationship between brain activity and anatomic
sites where this takes place, allowing the characterisation of the physiological
activity of the cortical brain layers as well as to study the plastic
reorganisation of the brain in different pathological conditions following
stroke, limb amputation, spinal cord injury, hemisperectomy.
PMID- 11011063
TI - Processing of multiple kinematic signals in the cerebellum and motor cortices.
AB - The cerebellum and motor cortices are hypothesized to make fundamentally
different but synergistic contributions to the control of movement. Richly
interconnected, these structures must communicate and translate salient
parameters of movement. This review examines the similarities and differences in
the encoding of multiple limb movement parameters in the cerebellum and motor
cortices. Also presented are recent data on direction and speed coding by
cerebellar Purkinje cells and primary motor and dorsal premotor cortical neurons
during a visually-instructed, manual tracking task. Both similarities and
differences have been found in the way that these two motor areas process
movement parameters. For example, the two motor control structures encode
direction with almost identical depths of modulation, which may simplify the
exchange of directional signals. Two major differences between the cerebellum and
motor cortices consist of the distribution of the preferred directions and the
manner in which direction and speed are jointly signaled within the discharge of
individual neurons. First, an anterior-posterior distribution of preferred
directions has been shown for both reaching and manual tracking, consistent with
an intrinsic reference frame and/or the structure of afferent input. In contrast,
neurons in the motor cortices have uniformly distributed preferred directions,
consistent with general purpose directional calculations. Secondly, Purkinje
cells in the cerebellum and motor cortices combine movement direction and speed
information differently. For example, Purkinje cell discharge encodes
combinations of direction and speed, a 'preferred velocity', while the motor
cortical neurons use a temporal parcellation scheme to encode multiple parameters
of movement. These results demonstrate that the cerebellum and motor cortices
process and use kinematic information in fundamentally different ways that may
underlie the functional uniqueness of the two motor control structures.
PMID- 11011064
TI - Molecular mechanisms regulating the retrograde axonal transport of neurotrophins.
AB - Neurotrophins are released from target tissues following neural innervation and
bind to specific receptors situated on the nerve terminal plasma membrane. The
neurotrophin-receptor complex undergoes retrograde axonal transport towards the
cell soma, where it signals to the nucleus. This process allows neurotrophins to
perform their numerous functions, which include the promotion of neuronal
survival and the outgrowth of axons towards certain target tissues. The molecular
events controlling each of the components of retrograde axonal transport are
beginning to become defined. There is good evidence for the participation of
phosphatidylinositol 3-kinase, phosphatidylinositol 4-kinase and the actin
cytoskeleton in neurotrophin retrograde axonal transport in vivo. It also appears
that the retrograde motor protein dynein mediates the retrograde axonal transport
in vivo of neurotrophins such as nerve growth factor. This review discusses the
role of the neurotrophin receptors in binding and axonal transport, the endocytic
processes required for neurotrophin internalization, the targeting and
trafficking of neurotrophins, and the propagation of neurotrophin-induced signals
along the axon.
PMID- 11011065
TI - Chemoarchitecture of the anuran auditory midbrain.
AB - The anuran torus semicircularis consists of several subnuclei that are part of
the ascending auditory pathway as well as audiomotor interface structures.
Additionally, recent anatomical studies suggest that the midbrain tegmentum is an
integral part of the audiomotor network. To describe the chemoarchitecture of
these nuclei, taking into account the toral subdivisions, we investigated the
distribution of serotonin, leucine-enkephalin, substance P, tyrosine-hydroxylase,
dopamine D2-receptor, parvalbumin, aspartate, GABA, and estrogen-binding protein
immunoreactivity in the midbrain of Bombina orientalis, Discoglossus pictus and
Xenopus laevis. In the torus semicircularis, the highest density of
immunoreactive fibers and terminals for all transmitters was found in the laminar
nucleus. Parvalbumin-like immunoreactivity was highest in the principal nucleus,
and D2-receptor-like immunoreactivity was uniformly distributed throughout the
torus. In the tegmentum, axons and/or dendrites were stained with all antibodies
except estrogen-binding protein. Additionally, heavily stained enkephalin and
substance P-immunopositive fiber plexus were found in the lateral and dorsal
tegmentum. The immunostainings revealed no qualitative differences between the
three species. Immunopositive cell bodies were labeled in several brain areas,
the connectivity of which with torus and tegmentum is discussed on the background
of functional questions. The putative neuromodulatory innervation of both the
laminar nucleus of the torus semicircularis and the tegmentum may be the
anatomical basis for the influence of the animal's endogenous state on the
behavioral reaction to sensory stimuli. These data corroborate earlier anatomical
and physiological findings that the neurons of these nuclei are key elements in
the audio-motor interface.
PMID- 11011066
TI - Neurotrophic factors in Alzheimer's and Parkinson's disease brain.
AB - The biomedical literature on the subject of neurotrophic growth factors has
expanded prodigiously. This essay reviews neurotrophic factors (NTF) and their
receptors in Alzheimer's disease (AD) and Parkinson's disease (PD) brain and
recent updates on receptor signaling. The hypotheses for specific NTF involvement
in neurodegenerative diseases in human and as potential therapy are based mainly
on experimental animal and in vitro models. There are wide gaps in information on
regional synthesis and cell contents of NTFs and their receptors in human brain.
Observations on AD brain indicate increases in NGF and decreases in BDNF in
surviving neurons of hippocampus and certain neocortical regions and decreases in
TrkA in cortex and nucleus basalis. In PD brain, the few data available indicate
decreases in neuronal content of GDNF and bFGF in surviving substantia nigra
dopaminergic neurons. There are very few data regarding age-dependent effects on
NTFs and on their receptors in human brain. Since NTFs in neurons are subject to
retrograde and, in at least some cases, to anterograde transport from and to
target neurons, their effects may be related to synthesis in local or remote
sites or to changes in axoplasmic transport. Also, certain NTFs and their
receptors are found to be expressed in activated glia. Thus, comparative in situ
data for transcription levels and protein contents for NTFs and their receptors
in both sites of neuronal origin and termination in human brain are needed to
understand their potential roles in treating human diseases.
PMID- 11011067
TI - Cortistatin: a member of the somatostatin neuropeptide family with distinct
physiological functions.
AB - Cortistatin is a recently discovered neuropeptide relative of somatostatin named
after its predominantly cortical expression and ability to depress cortical
activity. Cortistatin-14 shares 11 of the 14 amino acids of somatostatin-14 yet
their nucleotide sequences and chromosomal localization clearly indicate they are
products of separate genes. Now cloned from human, mouse and rat sources,
cortistatin is known to bind all five cloned somatostatin receptors and share
many pharmacological and functional properties with somatostatin including the
depression of neuronal activity. However, cortistatin also has many properties
distinct from somatostatin including induction of slow-wave sleep, apparently by
antagonism of the excitatory effects of acetylcholine on the cortex, reduction of
locomotor activity, and activation of cation selective currents not responsive to
somatostatin. Expression of mRNA encoding cortistatin follows a circadian rhythm
and is upregulated on deprivation of sleep, suggesting cortistatin is a sleep
modulatory factor. This review summarizes recent advances in our understanding of
the neurobiology of cortistatin, examines the similarities and differences
between cortistatin and somatostatin, and asks the question: does cortistatin
bind to a cortistatin-specific receptor?
PMID- 11011068
TI - Female gonadal hormones, serotonin, and sexual receptivity.
AB - The inhibitory and facilitatory effect of serotonergic (5-HT) receptor agonists
and antagonists on the female rat lordosis reflex is reviewed. Emphasis is placed
on the role of 5-HT(1A) and 5-HT(2) receptors. The effect of estrogen and
progesterone on the lordosis response to 5-HT receptor-selective compounds is
reviewed and potential mechanisms for hormonal modulation of the 5-HT system are
suggested. Evidence that 5-HT modifies the female's position relative to a
threshold for lordosis is presented. Finally, it is hypothesized that 5-HT's dual
regulation of lordosis contributes to the female's ability to regulate mating
behavior so that it occurs under physiological and environmental conditions that
are conducive for individual, as well as species, survival.
PMID- 11011069
TI - Adenosine: does it have a neuroprotective role after all?
AB - A neuroprotective role for adenosine is commonly assumed. Recent studies revealed
that adenosine may unexpectedly, under certain circumstances, have the opposite
effects contributing to neuronal damage and death. The basis for this duality may
be the activation of distinct subtypes of adenosine receptors, interactions
between these receptors, differential actions on neuronal and glial cells, and
various time frames of adenosinergic compounds administration. If these aspects
are understood, adenosine should remain an interesting target for therapeutical
neuroprotective approaches after all.
PMID- 11011070
TI - The pharmacology of latent inhibition as an animal model of schizophrenia.
AB - The nature of the primary symptoms of schizophrenia and our lack of knowledge of
its underlying cause both contribute to the difficulty of generating convincing
animal models of schizophrenia. A more recent approach to investigating the
biological basis of schizophrenia has been to use information processing models
of the disease to link psychotic phenomena to their neural basis. Schizophrenics
are impaired in a number of experimental cognitive tasks that support this
approach, including sensory gating tasks and models of selective attention such
as latent inhibition (LI). LI refers to a process in which noncontingent
presentation of a stimulus attenuates its ability to enter into subsequent
associations, and it has received much attention because it is widely considered
to relate to the cognitive abnormalities that characterise acute schizophrenia.
Several claims have been made for LI having face and construct validity for
schizophrenia. In this review of the pharmacological studies carried out with LI
we examine its claim to predictive validity and the role of methodological
considerations in drug effects. The data reviewed demonstrate that facilitation
of low levels of LI is strongly related to demonstrated antipsychotic activity in
man and all major antipsychotic drugs, both typical and atypical, have been shown
to potentiate LI using a variety of protocols. Very few compounds without
antipsychotic activity are active in this model. In contrast, disruption of LI
occurs with a wide range of drugs and the relationship with psychotomimetic
potential is less clear. Although reversal of disrupted LI has also been used as
a model for antipsychotic acticity, mostly using amphetamine-induced disruption,
insufficient studies have been carried out to evaluate its claim to predictive
validity. However, like facilitation, it is sensitive to both typical and
atypical antipsychotic agents. The data we have reviewed here demonstrate that
facilitation of LI and, perhaps to a lesser extent, reversal of disrupted LI
fulfil the criteria for predictive validity.
PMID- 11011071
TI - Catecholamine systems in the brain of vertebrates: new perspectives through a
comparative approach.
AB - A comparative analysis of catecholaminergic systems in the brain and spinal cord
of vertebrates forces to reconsider several aspects of the organization of
catecholamine systems. Evidence has been provided for the existence of extensive,
putatively catecholaminergic cell groups in the spinal cord, the pretectum, the
habenular region, and cortical and subcortical telencephalic areas. Moreover,
putatively dopamine- and noradrenaline-accumulating cells have been demonstrated
in the hypothalamic periventricular organ of almost every non-mammalian
vertebrate studied. In contrast with the classical idea that the evolution of
catecholamine systems is marked by an increase in complexity going from
anamniotes to amniotes, it is now evident that the brains of anamniotes contain
catecholaminergic cell groups, of which the counterparts in amniotes have lost
the capacity to produce catecholamines. Moreover, a segmental approach in
studying the organization of catecholaminergic systems is advocated. Such an
approach has recently led to the conclusion that the chemoarchitecture and
connections of the basal ganglia of anamniote and amniote tetrapods are largely
comparable. This review has also brought together data about the distribution of
receptors and catecholaminergic fibers as well as data about developmental
aspects. From these data it has become clear that there is a good match between
catecholaminergic fibers and receptors, but, at many places, volume transmission
seems to play an important role. Finally, although the available data are still
limited, striking differences are observed in the spatiotemporal sequence of
appearance of catecholaminergic cell groups, in particular those in the retina
and olfactory bulb.
PMID- 11011072
TI - Role of phospholipase A(2) on the variations of the choline signal intensity
observed by 1H magnetic resonance spectroscopy in brain diseases.
AB - Phospholipase A(2) catalyzes the hydrolysis of membrane glycerophospholipids
leading to the production of metabolites observable by both 1H and 31P magnetic
resonance spectroscopy. The signal of choline-containing compounds (Cho) observed
by 1H magnetic resonance spectroscopy is constituted of metabolites of
phosphatidylcholine, especially phosphocholine (PCho) and glycerophosphocholine
(GPCho). The phosphomonoester (PME) and phosphodiester (PDE) signals observed by
31P magnetic resonance spectroscopy are, respectively, precursors and catabolites
of phospholipids. A large number of brain diseases have been reported to cause
variations in the intensity of the Cho, PME and PDE signals. Changes in the
activity of phospholipase A(2) have been measured in many brain diseases. In this
review, the relationships between the results of 1H and 31P magnetic resonance
spectroscopy and the phospholipase A(2) assays are analyzed. In many brain
diseases, the variation in the Cho signal intensity can be correlated with a
stimulation or inhibition of the phospholipase A(2) activity.
PMID- 11011073
TI - Local regulation of T cell numbers and lymphocyte-inhibiting activity in the
interstitial tissue of the adult rat testis.
AB - The testis is an immunologically privileged site, and transplantation data
suggest that this privilege may be enhanced in cryptorchidism. Although
alphabetaT cells, which mediate and promote the immune response, have access to
the normal testis, relatively little is known about these cells in the
abdominally located testis. An increase in testicular lymphocyte-inhibiting
cytokines has also been implicated in enhanced graft survival following the
experimental induction of cryptorchidism. Consequently, T cell traffic and
lymphocyte-inhibiting activity in testes of cryptorchid adult rats were examined
in the following study. Numbers of alphabetaT cells and the cytotoxic CD8(+) T
cell subset in the testis were unaffected following 1 month of cryptorchidism. In
contrast, subcutaneous testosterone implants, which inhibit Leydig cell function
through suppression of gonadotrophin secretion, reduced these parameters in both
scrotal and abdominal testes. Testicular T cell numbers were positively
correlated with the number of testicular resident macrophages, which also were
reduced by subcutaneous testosterone implants. The concentration of lymphocyte
inhibiting activity in the testicular interstitial fluid was reduced by 80% in
short-term (1 month) and longer-term (3 months) cryptorchidism. These data
indicate that the T cell population, and in particular the CD8(+) T cell subset,
in the rat testis is functionally related to the resident macrophages or Leydig
cells. On the other hand, testicular lymphocyte-inhibiting activity does not
appear to be a determinant of the number of testicular T cells, and may not be a
major factor in the prolonged survival of certain grafts in the abdominal testis.
PMID- 11011074
TI - Ability of recombinant human TNF binding protein-1 (r-hTBP-1) to inhibit the
development of experimentally-induced endometriosis in rats.
AB - The aim of this study was to assess whether r-hTBP-1 (recombinant human tumor
necrosis factor binding protein-1), the soluble form of tumor necrosis factor
alpha (TNF) receptor type 1 might be effective in counteracting the proliferation
of ectopic endometrium using an in vivo experimental model of endometriosis. The
in vivo model involved transplanting a square fragment of autologus uterine
tissue onto the inner surface of the abdominal wall in rats. r-hTBP-1 was
administered for 1 week at 10 mg/kg, s.c. divided into two daily injections. The
gonadotropin-releasing hormone antagonist antide was used for reference and given
at the dose of 2 mg/kg, s.c. every 3 days for 1 week. The animals were killed 2
and 9 days after the last treatment and the size of endometriotic implants
measured. Blood samples and spleens were also taken for assessment of estradiol
17beta levels and natural killer (NK) activity in vitro against murine YAC cells,
respectively. The results of this study indicate that r-hTBP-1 is effective in
reducing the size of the endometriotic-like foci mainly at the later sacrifice
time-point when they were significantly decreased by 64% as compared to control
animals. As expected, antide induces an almost complete and statistically
significant remission both at the 2-day (94%) and the 9-day (88%); sacrifice time
point. Histological examination indicates that, compared to controls, r-hTBP-1
induces a slightly increased degeneration of the stromal tissues of the implants
at both examination times and, limitedly to the earlier observation time, of the
mucosal epithelium. No differences in the spleen cell NK activity were observed
at either sacrifice time-points in any treatment group. Estradiol-17beta
concentrations are significantly decreased in the antide-treated groups only at 9
days while no statistically significant changes are found in the animals
receiving r-hTBP-1. The results of this study carried out in a rat experimental
model of endometriosis provide evidence of the potential effectiveness of r-hTBP
1 in this pathological condition and support the role of TNF in its development.
PMID- 11011075
TI - Activation and deposition of human breast-milk complement C3 opsonins on serum
sensitive Escherichia coli 0111.
AB - Little is known about the physiological roles and contribution of the human
breast-milk complement system in the protection of both the maternal mammary
gland and the nursing infant. The ability of a serum-sensitive Escherichia coli
to activate the complement components of human breast-milk and colostrum was
assessed in vitro. The consequent deposition of C3 fragments, C3b, iC3b and C3dg,
on the bacteria was analysed, using a slight modification of a standard ELISA
technique for the assessment of activated C3 fragments. The deposition C3
fragments from human milk were demonstrated on the killed bacteria, E. coli NCTC
8007, serotype 0111 K58(B4) H2, using buffers with and without detergent,
supporting both the classical and alternative pathways of complement activation.
The milk fat appears to competitively inhibit the deposition of these opsonins on
the solid-phase bacteria. This study suggests that the complement system is able
to contribute to the increased resistance of breast-fed infants against
infections.
PMID- 11011076
TI - Simplified procedure for detection of enteric pathogenic viruses in shellfish by
RT-PCR.
AB - Epidemiological evidence linking the transmission of enteric viral disease to
shellfish has been known for a long time. A variety of methods have been
described for the detection of viral contaminants in shellfish using RT-PCR.
However, these methods generally include numerous, often fastidious and time
consuming steps for virus release from shellfish tissues and viral RNA isolation.
A simplified procedure based on the enzymatic liquefaction of shellfish digestive
tissues without any mechanical homogenisation step, followed by a simple
clarification of the lysate using dichloromethane extraction, was developed.
Viral RNA is isolated directly from the shellfish extract by a guanidium
thiocyanate-silica extraction method, adapted for the use of a vacuum manifold
system. Virus-specific RT-PCR assays were set up for detection of genomic
sequences of the predominant viral pathogens, HAV, Astrovirus and Norwalk-like
viruses (from genogoups I or II). The specificity of the amplicons is confirmed
finally by hybridisation with DIG-labelled specific probes. The overall procedure
applied to shellfish samples spiked with HAV particles allowed a detection of 20
pfu of HAV per g of hepatopancreas. In addition, up to 20 samples can be tested
within 24 h.
PMID- 11011077
TI - HCV RNA levels in hepatocellular carcinomas and adjacent non-tumorous livers.
AB - To determine the antiviral effects of drugs targeted to hepatitis C virus (HCV)
in chronic hepatitis patients, an accurate quantitative method with high
sensitivity is needed. Reverse transcription nested polymerase chain reaction (RT
PCR) is the most sensitive method for the detection of HCV sequences in clinical
specimens. However, this method is not quantitative. For this purpose, a
quantitative competitive assay was developed that combines RT and PCR followed by
image analysis to quantify HCV RNA. This assay targets the highly conserved 5'
non-coding region of HCV and is based on the co-amplification of wild type HCV
RNA with known amounts of mutant synthetic RNA. The mutant internal control used
in these experiments differs from the wild type RNA by two nucleotide
substitutions, which introduces an internal restriction enzyme site. In this
report, this method was used to determine the levels of positive strand RNA in 11
HCV positive hepatocellular carcinomas (HCC) and compared these with adjacent non
tumorous liver tissue. To confirm that the difference in viral titers is not
related to variations in the amount of RNA used in the assay, glyceraldehyde 3
phosphate dehydrogenase (GAPDH) mRNA was also assessed by competitive RT-PCR in
all tissue extracts. Using this competitive assay it was determined that HCV RNA
levels in the liver and tumor samples ranged from 10(3) to 10(6) molecules per
microg of total RNA which is similar to previous reports. Interestingly, the
amount of HCV in all the non-tumorous liver specimens were found to be
significantly higher (P<0.05) than the surrounding tumors, while the GAPDH mRNA
levels were found to be similar in both liver and tumor. Competitive RT-PCR is a
sensitive, accurate and reliable method to determine HCV titers in clinical
specimens. Using this method it was determined that malignant tumor cells harbor
less HCV as compared with the surrounding non-tumorous liver cells.
PMID- 11011078
TI - The use of phylogenetic data to develop molecular tools for the detection and
genotyping of Yam mosaic virus. Potential application in molecular epidemiology.
AB - Molecular detection of Yam mosaic virus (YMV), the most important potyvirus for
yam plants (Dioscorea spp.) has been limited by its high genetic diversity.
According to recent phylogenetic data, suitable molecular tools were developed
for detection and genotyping. A reliable and rapid molecular test is described
using single-tube immunocapture (IC)-RT-PCR combining the use of a monoclonal
antibody able to recognise all YMV serotypes and primers designed to take into
account the whole variability of YMV. Phylogenetic data were then used to develop
an uncoupled IC-RT-PCR procedure adapted to the genotyping of the three major
phylogenetic groups and the two recombinants implicated in the YMV epidemics in
the Caribbean and French Guiana. A third exploitation of phylogenetic data was
carried out with the development of a typing test based on the analysis of short
nucleotide sequences. The direct sequencing of a 450 nts fragment constituted a
reliable complementary typing tool as the resulting information was quite similar
to that obtained with sequences of the complete coat protein gene. The approach,
consisting in a robust study of YMV variability followed by the use of
phylogenetic data to develop reliable detection and genotyping tools, offers new
perspectives for powerful molecular epidemiological studies.
PMID- 11011079
TI - Improved RNA extraction and one-tube RT-PCR assay for simultaneous detection of
control plant RNA plus several viruses in plant extracts.
AB - A procedure was developed for simultaneous detection of plant RNA viruses and of
plant RNA, as a control. RT-PCR amplification with primers designed for the
detection of the plant mRNAs encoding malate dehydrogenase (MDH) and the large
subunit of ribulose bisphosphate carboxylase oxygenase (RubiscoL) was used for
the development of a plant extraction procedure that consistently yields extracts
that can be amplified. The control amplification was used successfully on
extracts from cane, leaf and/or bud tissues from grapevine, apple, raspberry,
strawberry, peach, apricot, plum and wheat. Multiplex RT-PCR conditions were
established for the simultaneous detection in grapevine extracts of either arabis
mosaic virus, rupestris stem pitting associated virus and malate dehydrogenase
mRNA, or grapevine virus A, grapevine virus B, grapevine leafroll associated
virus-3, and RubiscoL mRNA.
PMID- 11011080
TI - Determination of tumor necrosis factor-alpha levels in dengue virus infected
patients by sensitive biotin-streptavidin enzyme-linked immunosorbent assay.
AB - A modified sandwich enzyme-linked immunosorbent assay using biotin-streptavidin
system (BS-ELISA) was developed to determine levels of tumor necrosis factor
alpha (TNF-alpha) in serum samples of children infected with dengue virus (n=99)
and healthy controls (n=41). The minimum detectable concentration of TNF-alpha by
the BS-ELISA was 3.3 pg/ml. The mean TNF-alpha level was highest in those
patients with dengue shock syndrome (DSS) or dengue hemorrhagic fever (DHF) grade
III (37.44+/-42.0 pg/ml). Lower levels were found in DHF grade I (28.44+/-42.7
pg/ml), DHF grade II (24. 21+/-25.4 pg/ml) and dengue fever (DF) (14.10+/-24.0
pg/ml). TNF-alpha in the sera of DF and DHF patients could be detected on days 2
6 after the onset of fever, the high level occurring on day 5. TNF-alpha was
detected in 41.4% (24.01+/-35.2 pg/ml) of dengue virus infected patients and 7.3%
(4.2+/-15.6 pg/ml) of control subjects. The sera of patients contained
significantly higher levels of TNF-alpha than the sera of controls, P
value<0.001. DHF patients had significantly higher levels of TNF-alpha than DF
patients (P-value=0.020) but no difference in the TNF-alpha levels from sera of
DHF grades I-III patients was observed (P-value=0.295). The results indicate that
the BS-ELISA is a very sensitive method for determining TNF-alpha in serum
samples of DF and DHF patients. The TNF-alpha levels might be associated with
dengue virus infection and related to disease severity of DHF.
PMID- 11011081
TI - A comparative analysis of freon substitutes in the purification of reovirus and
calicivirus.
AB - Freon 113 (Freon) is an essential component used in some viral purification
methods to separate virus from infected cell debris. With its environmental and
toxic hazards, Freon's availability is limited and more tightly regulated.
Several organic solvent substitutes were selected to identify a suitable Freon
replacement for the purification of both cultivable reovirus and fastidious
calicivirus. Reovirus was extracted from tissue cultured cells with each solvent
tested and purified in cesium chloride gradients by standard techniques. Purified
virions were analyzed for conservation of physical and biological properties by
morphological examination and infectivity studies. The purification of
calicivirus nucleic acid from stool samples using selected solvents was also
examined. Solvent-extracted calicivirus RNA was reverse transcribed and
quantified by polymerase chain reaction amplification of a standard diagnostic
117 bp amplicon. These studies indicated that Vertrel XF (a newly developed
environmentally friendly Freon substitute) and a 7:3 mixture of isopentane/1
chlorobutane are suitable replacements. Considerations of flammability and ease
of use suggest that Vertrel XF is the preferred choice as a Freon substitute for
the purification of these non-enveloped viruses.
PMID- 11011082
TI - Development of an immunomagnetic capture reverse transcription-PCR assay for the
detection of Norwalk virus.
AB - Norwalk virus (NV) is the prototype human virus of the family Caliciviridae. A
rapid immunomagnetic capture/reverse transcription-(IMC/RT-)PCR assay was
developed for the detection of NV. Immunomagnetic capture (IMC) utilizes
paramagnetic beads coupled to a virus-specific antibody and allows separation of
virus from contaminating materials and virus concentration in a single step. The
detection limit of the developed assay was approximately 250-750 genomic
equivalents/ml of 10% stool suspension. The detection limit of the assay was not
altered by the presence of excess hepatitis A virus (HAV), although non-specific
binding of HAV to the paramagnetic beads was observed. A panel of 100 stools from
experimental human infections was screened for NV using a previously described
heat release method, an antigen ELISA, or IMC/RT-PCR. NV was detected in 65/100
of these samples by IMC/RT-PCR compared to only 38/99 by heat release and 31/95
by antigen detection ELISA. All samples that were negative by IMC were also
negative by both heat release and antigen ELISA. The number of samples in which
RT-PCR was inhibited was greatly reduced by the use of IMC/RT-PCR compared to the
heat release method (1/100 and 16/95 samples inhibited, respectively). The
ability of IMC to concentrate virus (> or =2000-fold greater than heat release)
and effectively remove inhibitory substances gives this assay distinct advantages
over both the heat release and antigen ELISAs.
PMID- 11011083
TI - Development of an RT-PCR diagnostic test for an avian astrovirus.
AB - Astroviruses are small round viruses that cause enteric disease in the young of
several species. Detection and diagnosis of astrovirus infection in non-human
hosts relies heavily on electron microscopy and fluorescent antibody tests.
Recently, our laboratory isolated and sequenced an avian astrovirus from poult
enteritis mortality syndrome affected turkeys. These studies describe the
development of RT-PCR methods, which specifically detect regions of the viral
capsid and polymerase genes, and demonstrate their use in detecting astrovirus
infection in commercial turkey flocks.
PMID- 11011084
TI - Packaging of small molecules into VP1-virus-like particles of the human
polyomavirus JC virus.
AB - Recombinantly expressed VP1-virus-like particles (VP1-VLP) of human polyomavirus
JC virus (JCV) were described recently as a new DNA transporter system. It was
shown that DNA molecules could be packaged into VP1-VLP during a controlled
chemical reassociation/dissociation process. In the present study VP1-VLP were
studied as carriers for pharmaceutical substances. Propidium iodide (PI) was
packaged into VP1-VLP as a reporter molecule. The PI-containing VP1-VLP could be
detected directly by flow cytometry. The fluorescence intensity of the VP1-VLP
depended strongly on the initial PI concentration. This packaging method is easy
to handle and applicable to viruses and VP1-VLP which can be dissociated and
reassociated chemically.
PMID- 11011085
TI - Use of electron microscopic and immunogold labeling techniques to determine
polyomavirus recombinant VP1 capsid-like particles entry into mouse 3T6 cell
nucleus.
AB - Murine polyomavirus major structural protein VP1 could assemble into capsid-like
particles when expressed in the baculovirus system. The recombinant capsid-like
particles that were purified by CsCl density gradient centrifugation were capable
of packaging host DNA. Electron microscopic and immunogold labeling techniques
were used to study the entry of these VP1 recombinant capsid-like particles into
mouse 3T6 cells. It was found that these VP1 recombinant capsid-like particles,
which lack polyomavirus minor structural proteins (VP2 and VP3), use the same
mechanism to enter mouse 3T6 cell cytoplasm and nucleus as that used by native
polyomavirus virions.
PMID- 11011086
TI - Elimination of HIV-1 plasmid DNA from virus samples obtained from transfection by
calcium-phosphate co-precipitation.
AB - Molecular genetics is a powerful tool to analyze the replication cycle of human
immunodeficiency virus type 1 (HIV-1). Culture fluids obtained from HIV-1 plasmid
transfected cells by calcium-phosphate co-precipitation were treated with
ethyleneglycol bis (beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) and
DNase I to obtain HIV-1 stocks virtually free of input plasmid DNAs. Even after
amplification by polymerase chain reaction (PCR), no plasmid DNA was detected in
cells following infection with EGTA/DNase I-treated virus samples. This method is
particularly useful for the examination of the early replication phase of HIV-1
by PCR.
PMID- 11011087
TI - Leaf secretion composition of the mangrove species Avicennia germinans (L.) in
relation to salinity: a case study by using total-reflection X-ray fluorescence
analysis.
AB - The aim here was to use total-reflection X-ray fluorescence (TXRF) to determine
the elemental composition (besides Na), and the relative contribution of each
element in leaf secretion of the mangrove species Avicennia germinans, grown
under contrasting salinities (0-865 mol m(-3) NaCl). Na was determined by
conventional atomic absorption spectrometry (AAS). Total secretion was 2.00+/
0.28 mmol m(-2) per day in control plants (at 0 NaCl) and increased progressively
up to 46.87+/-7.14 mmol m(-2) per day at 865 mol m(-3) NaCl. Na and Cl accounted
for 85.91+/-1.81% of the total secretion in control plants and about 96.32+/
0.30% in salt-treated plants. The excretion of Na exceeded that of Cl when
salinity increased and this led to a progressive increase in Na/Cl ratios from
0.46+/-0.02 in control plants up to 2.75+/-0.42 (at 865 mol m(-3) NaCl). Other
elements were also secreted in sizeable amounts such as K, S, Ca, Br and Zn.
However, the relative importance of these elements, in terms of total secretion,
was considerable in control plants (15% of the total secretion) and declined
significantly under salinity treatments (<5% of the total secretion). In
conclusion, TXRF has been shown to be a powerful tool allowing quantitative
determination of Cl (1.2-13 mmol m(-2) per day), secreted in relatively large
quantities, as well as other elements secreted in intermediate (S, Ca and K; 0.07
1.00 mmol m(-2) per day) and in trace quantities (Br and Zn; 0.6-4 umol m(-2) per
day).
PMID- 11011088
TI - An efficient method for the production of transgenic plants of peanut (Arachis
hypogaea L.) through Agrobacterium tumefaciens-mediated genetic transformation.
AB - Cotyledon explants from mature peanut seeds (Arachis hypogaea L.) were optimized
to obtain adventitious shoot buds with high frequencies (>90%). Efficient
transformation of these cotyledons by using Agrobacterium tumefaciens strain C58
carrying neomycin phosphotransferase II (nptII) and beta-glucuronidase (GUS;
uidA), or coat protein gene of the Indian peanut clump virus (IPCVcp) and nptII
on binary vectors (pBI121; pROKII:IPCVcp) led to the production of a large
percentage (55%) of transgenic plants. Transformed individuals were obtained
through selection on medium containing 125 mg l(-1) kanamycin. A large number of
independently transformed plants (over 75) were successfully transplanted to the
glasshouse. Integration of the transgenes and stable genetic transformants in the
progeny were assessed by PCR amplification of 700-bp fragment of nptII and 585-bp
of IPCVcp genes, and Southern blot hybridizations in the T1 generation of
transgenic plants. Analysis of 35 transgenic plants of T1 generation from the
progeny of a single transformation event suggested the segregation of a single
copy insert in a 3:1 Mendelian ratio. On an average, 120-150 days were required
between the initiation of explant transformation and transfer of rooted plants to
the greenhouse. The cotyledon regeneration system proved to be an excellent
vehicle for the production of a large number of independently transformed peanut
plants. Shoot formation was rapid and prolific, and a large proportion of these
shoots developed into fertile plants. The method reported here provides new
opportunities for the crop improvement of peanut via genetic transformation.
PMID- 11011089
TI - In vitro plant regeneration in Macroptilium atropurpureum, a legume with a broad
symbiont range for nodulation.
AB - Macroptilium atropurpureum is a model legume with a broad symbiont range for
nodulation. We have achieved the first in vitro plant regeneration of this
species using cv. Siratro. Hypocotyl explants excised from dark-grown seedlings
generated slimy, friable calli after three weeks' culture on B5 medium containing
1-2 mg/l kinetin and 0.05 mg/l alpha-naphthaleneacetic acid. This was followed by
the generation of green organogenic callus with shoot buds by subculturing the
explants to hormone-free B5 medium 20 days after the start of culture. The green
organogenic calli with shoot buds were maintained as organogenic callus by
subculturing on the same medium, and shoots were elongated on hormone-free B5
medium. Elongated shoots were rooted on half-strength B5 medium. Most regenerated
plants were morphologically normal, diploid and fertile, although tetraploid
plants appeared at a low frequency (8%).
PMID- 11011090
TI - Partial characterization and localization of a novel type of antifungal protein
(IWF6) isolated from sugar beet leaves.
AB - An antifungal protein was isolated from the intercellular washing fluid (IWF) of
leaves of sugar beet (Beta vulgaris L., cv. Monova) and purified to homogeneity.
The protein, IWF6, comprising 37 amino acids with six cysteines, was able to
inhibit the growth of the pathogen Cercospora beticola (Sacc.) in vitro, by 75%
after 120 h of growth at a concentration of 20 ug ml(-1). The amino acid sequence
data were used to generate a polymerase chain reaction (PCR) clone, employed for
the isolation of a corresponding cDNA clone. The cDNA encodes a precursor protein
with an N-terminal putative signal sequence of 45 amino acids, followed by the
mature protein of 37 amino acids. Antibodies raised against a synthetic peptide
covering the complete sequence of IWF6 were used in immunolocalization studies.
The protein was recognized by the antibody in nearly all leaf cell types except
epidermal cells. In necrotic tissue, the protein was mainly recognized on C.
beticola hyphae growing in a 'pellet' (ball-like) structure. The hyphal 'pellets'
are primarily located beneath the stomata. IWF6 shows less than 26% identity to
any previously described protein.
PMID- 11011091
TI - Pepper gene encoding a basic class II chitinase is inducible by pathogen and
ethephon.
AB - A chitinase cDNA clone (designated CAChi2) was isolated from the cDNA library of
pepper leaves infected with Xanthomonas campestris pv. vesicatoria. The 1004-bp
full-length CAChi2 cDNA encodes a basic chitinase with an N-terminal 24 amino
acid signal peptide followed by a catalytic region. An analysis of its sequence
indicates that CAChi2 is a class II chitinase, because it does not have chitin
binding domain and C-terminal extension sequences. The deduced amino acid
sequence of CAChi2 has a high level of identity with class II chitinases from
potato, tomato, tobacco and petunia. Southern analysis demonstrated that the
CAChi2 chitinase is encoded by a single or two copy genes in the pepper genome.
Following X. campestris pv. vesicatoria or Phytophthora capsici infection, the
CAChi2 chitinase mRNA was more highly expressed in the incompatible interaction,
compared to expression in the compatible interaction. Treatment with ethylene
releasing ethephon resulted in a strong accumulation of the transcripts in the
leaves. In contrast, DL-beta-amino-n-butyric acid, salicylic acid and methyl
jasmonate were not effective in inducing CAChi2 transcripts in pepper leaves.
PMID- 11011092
TI - Phytochrome and post-translational regulation of nitrate reductase in higher
plants.
AB - The possible influence of phytochrome on the activity state of nitrate reductase
(NR) was investigated in etiolated plants where the expression of the NR gene is
known to be under the control of phytochrome. Activity state is defined as NR
activity assayed in the presence of Mg(2+) as percentage of NR activity measured
in the absence of Mg(2+). This measurement is assumed to reflect non
phosphorylated NR as percentage of total NR. Beside etiolated barley and maize
leaves, a photosynthetic mutant of Lemna aequinoctialis was investigated and
compared with the wild type. The increase of NR activity following a red light
pulse, mediated via phytochrome, was confirmed in all etiolated plant species
investigated as well as in both strains of L. aequinoctialis cultivated in
glucose-containing medium. The effect of continuous red light surpassed the
effect of a single red light pulse in each case. However, the results did not
show any stimulating effect of phytochrome on the activity state caused by post
translational modulation. The activity state was strongly increased by continuous
red light in the wild type of L. aequinoctialis but not in the photosynthetic
mutant. These results show that the phytochrome system is not important for the
post-translational regulation of NR.
PMID- 11011093
TI - Growth promoting effect of two Sinorhizobium meliloti strains (a wild type and
its genetically modified derivative) on a non-legume plant species in specific
interaction with two arbuscular mycorrhizal fungi.
AB - In the present study, we have investigated whether the ubiquitous rhizosphere
soil organism Sinorhizobium meliloti has a plant growth promoting (PGP) effect on
non-leguminous plant species. Such PGP activity was investigated for both a wild
type strain and its genetically modified (GM) derivative, which had an enhanced
biofertilizer capability. The PGP effect of these rhizobial strains was tested in
interaction with two arbuscular-mycorrhizal (AM) fungi: G. mosseae or G.
intraradices on lettuce (Lactuca sativa L.) plants. Both rhizobial strains were
efficient in increasing lettuce biomass and also induced modifications on root
morphology, particularly in mycorrhizal plants; thus these strains behave as
plant growth promoting rhizobacteria. In non-mycorrhizal plants, both strains
exhibited a similar growth promoting effect on lettuce. However, both rhizobial
strains differed in mycorrhizal plants with regard to (i) biomass production,
(ii) the length of axis and lateral roots, and (iii) the number of lateral roots
formed; effects which were, in turn, affected by the AM fungus involved.
Microbial treatments were more effective on root growth and morphology at earlier
developmental stages (20 days of plant growth) but, in a later stage (after 40
days), the microbial effects were more relevant at increasing plant biomass. The
interaction between the GM rhizobial strain and G. mosseae produced the highest
growth promoting effect (476% over control), in spite of the fact that G.
intraradices showed a quicker and higher colonization ability than G. mosseae.
Microbial interactions inducing PGP effects did not benefit AM colonization nor
the succinate dehydrogenase activity in the AM fungal mycelium. Irrespective of
the underlying mechanisms, which are being now investigated, the interactions
between rhizobial strains, as free-living saprophs, and AM fungi are noteworthy,
and depend on the microbial genotype involved.
PMID- 11011094
TI - A DNA-binding activity for the promoter of the gene encoding C(4)
phosphoenolpyruvate carboxylase is modulated by phosphorylation during greening
of the Sorghum leaf.
AB - Electrophoresis mobility shift assay (EMSA) identified nuclear proteins with
binding activity to a 430 bp promoter fragment of the Sorghum C(4)
phosphoenolpyruvate carboxylase gene (SvC4). The DNA binding activities (two main
retarded bands; PC1 and PC2) were high in nuclear extracts from etiolated leaves,
decreased during greening and became very low or null in nuclear extracts from
green leaves. This process was found to be mediated by phytochrome and was
apparently irreversible since the DNA-binding activities were not restored in
green plants kept in continuous darkness. The AT-rich region of the promoter
fragment was identified to be the interaction domain of PC2. The detection of PC2
with EMSA was markedly reduced by preincubation of nuclear protein extracts with
Mg-ATP or Mg-GTP and restored in the presence of a general protein
serine/threonine-kinase inhibitor, K252a. The results suggested that the PC2
binding activity was modulated by phosphorylation during the greening process of
the Sorghum leaf.
PMID- 11011095
TI - Chilling stress-induced changes of antioxidant enzymes in the leaves of cucumber:
in gel enzyme activity assays.
AB - To investigate the antioxidant defense system, chilling stress-induced changes of
antioxidant enzymes were examined in the leaves of cucumber (Cucumis sativus L.).
Chilling stress preferentially enhanced the activities of the superoxide
dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR) and
peroxidase specific to guaiacol, whereas it induced the decrease of catalase
activity. In order to analyze the changes of antioxidant enzyme isoforms against
chilling stress, foliar extracts were subjected to native PAGE. Leaves of
cucumber had four isoforms of Mn-SOD and two isoforms of Cu/Zn-SOD. Fe-SOD
isoform was not observed in this plant. Expression of Cu/Zn-SOD and Mn-SOD was
preferentially enhanced by chilling stress. Expression of Mn-SOD-2 and -4 was
enhanced after 48 h of the poststress period. Five APX isoforms were presented in
the leaves of cucumber. The intensities of APX-4 and -5 were enhanced by chilling
stress, whereas that of APX-3 was significantly increased in the poststress
periods after chilling stress. Gel stained for GR activity revealed six isoforms
in the plant. Activation levels for most of GR isoforms were higher in the
stressed-plants than the control and poststressed-plants, but that of GR-1
isoform was significantly higher in the poststressed-plants than chilling
stressed-plants. These results collectively suggest that chilling stress
activates the enzymes of an SOD/ascorbate-glutathione cycle under catalase
deactivation in the leaves of cucumber, but the response timing of enzyme
isoforms against various environmental stresses is not the same for all isoforms
of antioxidant enzymes.
PMID- 11011096
TI - Analysis of grape ESTs: global gene expression patterns in leaf and berry.
AB - Analysis of 2479 ESTs from Vitis vinifera berry tissue and 2438 from leaf
revealed that 1% of the ESTs match to known Vitis proteins, 72% to plant
proteins, 11% to non-plant, and 16% had no match (P[N]>0.5). The levels of
redundancy were similar in the leaf and berry libraries. Only 12% of the genes
matched by the ESTs were common to both libraries indicating marked differences
in the genes expressed in the two tissues. The abundance of transcripts with
predicted cellular roles in leaf and berry were estimated by classifying the
primary BLAST matches to known proteins (score >80) into functional categories.
Thirty-six percent of the leaf transcripts were involved in photosynthesis,
compared to 3% in the berry. This is a much higher proportion of transcripts
involved with a function limited to specialized cells, than was found when
transcripts of 33 human tissues were compared using a similar approach,
suggesting plant cells may involve their cellular machinery to a greater extent
in specialized activities than animal cells. Relatively enhanced expression of
specific transcription factors, and genes involved in defense, detoxification,
stress response, proteolysis, trafficing, and signal transduction, suggests berry
tissue is actively engaged in responding to environmental stimuli.
PMID- 11011097
TI - Pepper gene encoding a basic beta-1,3-glucanase is differentially expressed in
pepper tissues upon pathogen infection and ethephon or methyl jasmonate
treatment.
AB - A basic beta-1,3-glucanase cDNA clone (CABGLU) was isolated from the cDNA library
constructed from hypersensitive response lesions of pepper leaves infected with
avirulent strain of Xanthomonas campestris pv. vesicatoria. The deduced
polypeptide of CABGLU which contains a C-terminal extension N-glycosylated at a
single site characterized as typical structure of class I beta-1,3-glucanase has
a high level of identity with tobacco basic beta-1,3-glucanase (77.4%), but only
a moderate level of identity with tomato acidic beta-1,3-glucanase (42.6%).
Genomic DNA gel blot analysis indicates that the pepper genome contains one or
two beta-1,3-glucanase copy genes. Transcripts of the CABGLU gene were more
induced in incompatible interactions than in compatible interactions, when
inoculated with X. campestris pv. vesicatoria or Phytophthora capsici.
Accumulation of CABGLU mRNA was strongly induced in pepper leaves by both
ethephon and methyl jasmonate. The CABGLU mRNA was constitutively expressed only
in the roots of all the plant organs. These data indicate that the basic beta-1,3
glucanase gene may be induced by pathogen attack and abiotic stresses.
PMID- 11011098
TI - Photosynthesis and antioxidant enzymes of phyllodes of Acacia mangium.
AB - Physiological processes are influenced by environmental factors and plant
characteristics. The distribution of photosynthetic capacity of phyllodes of
Acacia mangium Willd. seedlings was studied in relation to the in vivo
photosystem II (PSII) function, photosynthetic gas exchange, chlorophyll
fluorescence and activities of antioxidant enzymes (superoxide dismutase (SOD)
and ascorbate peroxidase (APX)) of phyllodes at different positions on seedlings.
There was a vertical gradient in photosynthetic capacity of phyllodes along the
shoot. Phyllode 1 (at the apex) showed negative carbon uptake at PPFD lower than
400 umol m(-2) s(-1). High photosynthetic capacities, chlorophyll concentrations,
DeltaF/F'(m), and q(P) were observed in phyllodes 4, 6 and 8. The high
photosynthetic capacities of mature phyllodes could be attributed to the enhanced
availability of CO(2) and the high efficiency of PSII in energy absorption and
utilization. Total SOD and APX activities (on a dry weight basis) were highest at
phyllode 1 and decreased as the phyllodes matured. The high photosynthetic
capacity and low respiration loss in mature phyllodes could be important factors,
responsible for the rapid establishment and fast growth of A. mangium in
reforestation programs.
PMID- 11011099
TI - Cerium and lanthanum promote floral initiation and reproductive growth of
Arabidopsis thaliana.
AB - The effects of cerium and lanthanum on the vegetative growth, floral initiation
and reproductive growth of Arabidopsis thaliana were studied. Addition of cerium
nitrate (0.5-10 uM) or lanthanum nitrate (0.5-50 uM) to the culture medium
significantly increased the lengths of primary roots, but had no significant
effects on the number of rosette leaves produced per plant, plant heights and dry
weights during the vegetative growth stage (17 days after seed germination). The
percentage of plants bolted was significantly increased with the addition of 0.5
10.0 uM cerium nitrate or lanthanum nitrate. The combination of 0.5 uM cerium
nitrate and 0.5 uM lanthanum nitrate was found to be most effective on the
induction of floral initiation. The height, dry weight and average number of
flower numbers of 35-day-old plants growing in media containing cerium nitrate
or/and lanthanum nitrate (0.5-10.0 uM) were found to be significantly higher than
those in the control medium. The endogenous levels of cytokinins (zeatin
riboside, dihydrozeatin riboside and isopentenyl adenosine) and carbohydrates
(sucrose, glucose and fructose) in leaf and root tissues of plants growing in the
medium supplemented with 0.5 uM cerium nitrate and 0.5 uM lanthanum nitrate were
not significantly different from those of plants in the control medium.
Application of 0.5 uM cerium nitrate and 0.5 uM lanthanum nitrate enhanced the
effects of 10(-6) M IPA on root growth, plant height and flowering. The role of
cerium and lanthanum in promoting floral initiation and reproductive growth and
the possibility of developing non-hormonal flowering promoting agents are
discussed.
PMID- 11011100
TI - Changes in amino acid composition and nitrogen metabolizing enzymes in ripening
fruits of Lycopersicon esculentum Mill.
AB - The free amino acid content of tomato (Lycopersicon esculentum Mill.) fruits from
cultivars Platense, Vollendung and Cherry were determined during ripening. It was
found that glutamate markedly increased in red fruits of the three cultivars
under study. At this stage, the cv Cherry had the highest relative glutamate
molar content (52%) of all the analyzed tomato fruit cultivars. Measurements of
nitrogen-assimilating enzyme activities of these fruits showed a decrease in
glutamine synthetase (GS, EC 6.3.1.2) during fruit ripening and a concomitant
increase in NADH-glutamate dehydrogenase (GDH, EC 1.4.1.3) and aspartate
aminotransferase (EC 2.6.1.1) activities. Western blot analysis of protein
extracts revealed that while GS was principally present in green fruit extracts,
GDH was almost exclusively observed in the extracts of red fruits. These results
suggest a reciprocal pattern of induction between GS and GDH during tomato fruit
ripening.
PMID- 11011101
TI - Characterization of salt-induced changes in gene expression in tomato
(Lycopersicon esculentum) roots and the role played by abscisic acid.
AB - Examination of tomato (Lycopersicon esculentum Mill) root mRNA profiles by
differential display-polymerase chain reaction (DD-PCR) revealed that a salt
treatment induced, promoted or repressed the expression of a number of genes. The
majority of the observed changes were indicative of a rapid and transient salt
induced alteration in gene expression. Twenty partial cDNAs corresponding
primarily to salt-induced or up-regulated mRNAs were subsequently cloned and
sequenced. The role of abscisic acid (ABA) in regulating salt-responsive gene
expression in roots was explored. The DD-PCR data indicate that the majority of
the salt-induced changes in the root mRNA profile occurred in an ABA-independent
manner. The expression of genes corresponding to six cDNAs was shown
unequivocally to be responsive to a salt treatment by RNA blot hybridization.
Just two of these were responsive to exogenous ABA and, in salt-treated roots of
the ABA-deficient mutant flacca, all were expressed to a level comparable to that
in the wild-type. The identity of two of the salt-responsive partial cDNAs is
known. The deduced amino acid sequence of one was similar to that of laccases
that polymerize a variety of substrates to form resilient structures within the
cell wall. One other shared amino acid sequence similarity with the C-terminus of
a tobacco pathogen-induced oxygenase (PIOX). It is possible that the PIOX is
involved in generating signaling molecules that mediate a general stress
response.
PMID- 11011102
TI - Significance of sulfhydryl groups in the activity of urease from pigeonpea
(Cajanus cajan L.) seeds.
AB - Titration of urease from pigeonpea (Cajanus cajan L.), a hexameric protein (mol.
wt. 480000; subunit mol. wt. 80000), with 5,5'-dithiobis-(2-nitrobenzoate) (DTNB)
reveals the presence of 5.82+/-0.13 'accessible' sulfhydryl groups per molecule
of the enzyme protein (i.e. about one 'accessible' SH group per subunit).
Denatured enzyme was found to titrate for 12.1+/-0.1 SH groups per molecule (i.e.
about two SH groups per subunit). Half of the 'accessible' groups react faster
than the remaining at pH 8.5 as well as pH 7.5. However, the reaction was slower
at pH 7.5 than 8.5. Time-dependent loss of enzyme activity with DTNB was also
found to be biphasic. The enzyme was inactivated at low concentration of p
chloromercuribenzoate (p-CMB), N-ethyl maleimide (NEM) and iodoacetamide. The
inactivation reactions were biphasic, with half of the activity lost more rapidly
than the remaining half. The loss of activity with p-CMB was linearly related to
the blocking of accessible SH groups. Inactivation by p-CMB is largely reversible
by addition of excess of cysteine. Fluoride ion strongly protects the enzyme
against NEM inactivation, however, substrate urea provides much weaker protection
against SH group reagents. The significance of these results is discussed.
PMID- 11011103
TI - Redox state and peroxidase system in sunflower plants exposed to ozone.
AB - Sunflower plants subjected to a short-term fumigation with O(3) (150 ppb for 4 h
repeated for 4 days) exhibited an increase in total ascorbate content,
accompanied by a marked oxidation of ascorbate, leading to a decrease in its
redox state, either at intracellular or extracellular level. O(3) exposure
induced a rise in free extracellular peroxidase (POD) activity, assayed by
syringaldazine as electron donor, as well as in the ionically and covalently cell
wall bound PODs. On the contrary, the activity of both extracellular and
intracellular guaiacol-POD did not show significant changes as a consequence of
the pollutant exposure. The stimulation of syringaldazine-POD activities may be
related to the effect of ozone on the growth of the cells, inducing an early
senescence through the activation or acceleration of lignification processes.
Beside, the reduced plasticity of the cell wall may oppose an unspecific
mechanical resistance against the abiotic stress induced by the ozone exposure.
PMID- 11011104
TI - A fuzzy-neural system for identification of species-specific alarm calls of
Gunnison's prairie dogs.
AB - In this study we describe the design and application of an automated
classification system that utilizes artificial intelligence to corroborate the
finding that Gunnison's prairie dogs have different alarm calls for different
species of predators. This corroboration is strong because it utilizes an
entirely different analysis technique than that used in the original research by
Slobodchikoff et al. [Slobodchikoff, C.N., Fischer, C., Shapiro, J., 1986.
Predator-specific alarm calls of prairie dogs. Am. Zool. 26, 557] or in
subsequent study done by Slobodchikoff et al. [Slobodchikoff, C.N., Kiriazis, J.,
Fischer, C., Creef, E., 1991. Semantic information distinguishing individual
predators in the alarm calls of Gunnison's prairie dogs. Anim. Behav. 42, 713
719]. The study described here also is more completely automated than earlier
study in this area. This automation allowed a large volume of field data to be
processed where all measurements of relevant parameters were performed through
software control. Previous study processed a smaller data set and utilized manual
measurement techniques. The new classification system, which combines fuzzy logic
and an artificial neural network, classified alarm calls correctly according to
the eliciting predator species, achieving accuracy levels ranging from 78.6 to
96.3% on raw field data digitized with low quality audio equipment.
PMID- 11011105
TI - Rats more readily acquire a time-of-day go no-go discrimination than a time-of
day choice discrimination.
AB - Male Sprague-Dawley rats were used to compare six time-place training procedures
that differed with respect to housing or training conditions. All procedures
involved training food-deprived rats to enter one choice arm of a T-maze during a
morning test session and to enter the other choice arm during an afternoon
session to obtain Cocoa Puffs(R). The task proved to be difficult. Only 39 of 49
rats attained a criterion of nine correct choices on ten consecutive trials
within a total of 120 trials. Making one choice arm distinct, limiting
consecutive same correct choices to two, giving one session during the light and
one during the dark portion of the light cycle, extinguishing perseveration of
the same choice responses, and housing the rats with a natural light cycle all
failed to significantly decrease the errors or trials to a 90% correct choice
criterion. In contrast, all responding rats (n=7) showed significantly better
than chance performance within 48 trials when the task was a go no-go
discrimination based on time of day. Learning to make a response during a session
when a choice to either choice arm is reinforced and to withhold responding
during a session when a choice to neither choice arm is reinforced was relatively
easy for the rats to acquire. Continued high level performance after the light
cycle was eliminated, a random feeding schedule was initiated, and other time
related cues were masked suggests that the rats used internal cues or an internal
clock to make the correct go or no-go response. It was concluded that rats are
prepared to use time of day as an occasion-setting stimulus, but have difficulty
using time of day as a signal for a specific response.
PMID- 11011106
TI - Prey catching in the archer fish: does the fish use a learned correction for
refraction?
AB - An answer to the question of how the archer fish hits an aerial insect, despite
the refraction of light at the surface of the water has not yet been found. The
aims of the present studies are to find out: (1) whether the fish applies a
learned correction with the virtual image as a point of reference; (2) whether
deprivation of practice in squirting affects performance. For the first aim the
accuracy of squirts was measured in 30 subjects. Contrary to suggestions from the
literature, elevation failures were prominent but the frequencies of over- and
under-squirting did not differ, which does not support the idea that the fishes
applied a learned correction for refraction by using feedback from the efficacy
of squirts. For the second aim, five experimental subjects were deprived of
practice, whereas six control subjects got daily practice, during 6 months. The
only significant difference, found thereafter, was that during the first session
experimental subjects aimed more often before squirting than control subjects
did, but hitting was not affected. A number of subjects developed abnormal
mandibles which inevitably led to squirting too high. Our findings do not support
the hypothesis that the archer fish uses learned corrections for refraction.
PMID- 11011107
TI - Influence of gender and behavioural lateralisation on two exploratory models of
anxiety in C3H mice.
AB - Behavioural lateralisation, which has been postulated to be an individual
personality trait, is related to the activity of various physiological systems
including the immune system. As lateralisation has been related to anxiety, which
is known to influence immune reactivity, it can be hypothesized that the relation
between lateralisation and immune reactivity involves individual behavioural
patterns as they appear in exploratory-based anxiety models. In order to answer
this question, a behavioural investigation focussing on exploratory activity was
undertaken in male and female C3H mice previously selected for their paw
preference. The observations were performed using two generic paradigms: elevated
plus-maze and open field. Exploratory behaviour in the open field, but not in the
plus-maze, was influenced by the interactive effect of gender and behavioural
lateralisation. A significant difference between male and female mice was found
in left-pawed but not in right-pawed nor ambidextrous animals, left-pawed female
mice displaying the less exploratory behaviours. These results provide a first
evidence of inter-individual variations in exploratory behaviours involving
interaction between gender and lateralisation.
PMID- 11011108
TI - Time estimation by pigeons on a fixed interval: the effect of pre-feeding.
AB - Pigeons well trained on a fixed interval 10-s schedule of reinforcement were
tested on the peak procedure. In a successive conditions design, they were either
pre-fed or not in the experimental setting. Pre-feeding decreased the rate of
responding. It also led to a maximum rate of responding that occurred 2-3 s later
than in the control condition, where the maximum occurred at the usual time of
reinforcement. The shift in peak time in response to pre-feeding shows that peak
time may not be a pure measure of timing. The results are also interpreted in
terms of timing theories.
PMID- 11011109
TI - Effects of auditory stimuli correlated with different probabilities of water
delivery in a limited-hold temporal schedule.
AB - Four rats were exposed to two different tone frequencies, each tone being
correlated with independent probabilities of water delivery in a temporally
defined schedule. The schedule consisted of a 60-s T cycle, with 30-s t(D) and
t(Delta) succesive subcycles. t(D) and t(Delta) were assigned complementary
probabilities of water delivery (1.0-0, 0.75-0.25, 0.5-0.5 and 1.0-0) in
succesive phases. Each of the first three experimental phases was followed by
five consecutive probe sessions using the same probability values, and in which
water was delivered independently of responding at the end of each subcycle.
Three additional rats were exposed to the same conditions, except that only one
tone was used in t(D) and t(Delta). The highest frequencies of responding were
observed in two of the rats exposed to differential tone frequencies, an effect
that was correlated with lower percentages of lost water deliveries, shorter
response latencies, and less variability in the intervals between successive
water presentations. In the last phase in which probabilities of water delivery
in t(D) and t(Delta) were 1.0 and 0, respectively, response frequency was always
higher in t(Delta). These results suggest that the number of water deliveries
obtained in the early cycles of every session were responsible for the total
number of responses and its correlated effects.
PMID- 11011110
TI - An evidence-based approach to prescribing NSAIDs in the treatment of
osteoarthritis and rheumatoid arthritis: The Second Canadian Consensus
Conference.
AB - The Second Canadian Consensus Conference was convened to discuss the latest
developments in the management of osteoarthritis (OA) and rheumatoid arthritis
(RA), and to make evidence-based recommendations, specifically regarding the use
of nonsteroidal anti-inflammatory drugs (NSAIDs) for these indications in primary
care practice. The recent availability of cyclo-oxygenase-2-specific inhibitors
has raised questions as to their role in the pharmacological management of OA and
RA, particularly in relation to conventional treatments such as acetaminophen and
nonspecific NSAIDs (with or without misoprostol or proton pump inhibitors). The
recommendations in this document, which were arrived at through critical review
of data from published randomized, clinical trials, deal with treatments of
choice, information to discuss with patients, use of NSAIDs in patients at risk
for serious upper gastrointestinal complications, renal or hepatic impairment or
congestive heart failure, appropriate follow-up, and the use of NSAIDs with anti-
hypertensives, warfarin, low dose acetylsalicylic acid and other medications. The
goal of these recommendations is to improve patient outcomes in the primary care
setting by maximizing treatment efficacy and minimizing rates of adverse events.
PMID- 11011111
TI - Polymerase chain reaction with confronting two-pair primers for polymorphism
genotyping.
AB - A novel PCR method using confronting two-pair primers, named PCR-CTPP, is
introduced to detect a single nucleotide polymorphism (base X or Y). One primer
for the X allele is set to include X' at the 3' end (antisense), where X' is the
antisense of X, with the counterpart sense primer upstream. For the Y allele, a
sense primer including Y at the 3' end is set, with the antisense primer
downstream. One common band and one specific band for each allele are amplified,
which allows genotyping directly by electrophoresis. This method is exemplified
by application to the polymorphisms of beta-adrenoceptor 2 and interleukin 1B. It
is simpler than PCR-RFLP (restriction fragment length polymorphism), which
requires incubation with a restriction enzyme, and is suitable for genotyping in
studies of genetic epidemiology involving hundreds of samples.
PMID- 11011112
TI - A novel gene "Niban" upregulated in renal carcinogenesis: cloning by the cDNA
amplified fragment length polymorphism approach.
AB - A modified AFLP (amplified fragment length polymorphism) method was employed to
isolate genes differentially expressed in renal carcinogenesis of Tsc2 gene
mutant (Eker) rats. One gene, selected for further investigation, was named
"Niban" "second" in Japanese), because it is the second new gene to be found
after Erc (expressed in renal carcinoma) in our laboratory. Importantly, "Niban"
is well expressed even in small primary rat Eker renal tumors, more than in
progressed cell lines, and is also expressed in human renal carcinoma cells, but
not in normal human or rat kidneys. Chromosome assignment was to RNO 13 in the
rat, and HSA 1. This "Niban" gene is a candidate as a marker for renal tumor,
especially early-stage renal carcinogenesis.
PMID- 11011113
TI - Absence of germline CHK2 mutations in familial gastric cancer.
AB - Recently, the CHK2 gene was identified as being a candidate gene responsible for
Li-Fraumeni syndrome (LFS). Gastric cancer is often clustered in families with
LFS, so it is possible that germline CHK2 mutation is also present in familial
gastric cancer (FGC). We therefore defined the genomic structure of the CHK2
gene, designed intronic primers, and searched for germline CHK2 mutations in 25
FGC cases by polymerase chain reaction-single strand conformational polymorphism
analysis of the entire coding region. In all of the 25 cases, at least two
siblings had histories of gastric cancer. There were no FGC cases that showed
germline CHK2 mutations. Thus, it was indicated that germline CHK2 mutations do
not contribute to the familial clustering of gastric cancer.
PMID- 11011114
TI - No association of the 5' promoter region polymorphism of CYP17 with breast cancer
risk in Japan.
AB - To examine the association between breast cancer risk and a T-to-C substitution
polymorphism at the 5' promoter region of CYP17, a case-control study was
conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144
histologically confirmed breast cancer patients diagnosed in the past 4 years and
166 hospital controls without cancer. Allele frequency among controls was 44.9%
(95% confidence interval; 39.5 - 50.2) for C allele. Odds ratio (OR) of the
polymorphism relative to TT-genotype was 0.97 (0.58 - 1.64) for TC-genotype and
0.81 (0.39 - 1.68) for CC-genotype. Subgroup analyses revealed that the OR was
not statistically significant for the subgroups stratified by interval after
diagnosis, age at menarche, age at first birth, menopausal status, body mass
index, and mother / sisters' history of breast cancer. Consistent with previous
studies conducted in other countries, the 5' promoter region polymorphism of
CYP17 affected breast cancer risk of Japanese women to a limited extent. Although
this is not a large-scale case-control study with population controls, these
findings provide enough information to discourage further studies on the
association between this polymorphism and breast cancer risk in Japan at large,
and suggest that this polymorphism is useless for breast cancer risk estimation.
PMID- 11011115
TI - Chemoprevention by nimesulide, a selective cyclooxygenase-2 inhibitor, of 2-amino
1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary gland
carcinogenesis in rats.
AB - Breast cancer is common in women all over the world, and exploration of
chemopreventive approaches to this cancer is very important. Nimesulide, a
selective inhibitor of cyclooxygenase-2 (COX-2), is a good candidate as a
chemopreventive agent with low toxicity. We examined its effects on mammary tumor
development in female Sprague-Dawley rats induced with the environmental
carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Rats at 7
weeks of age received intragastric intubations of PhIP (85 mg / kg body weight) 4
times weekly for 2 weeks and were maintained on control diet (high fat diet) or
experimental diet (high fat diet supplemented with 400 ppm nimesulide) throughout
the experiment. COX-2 protein was over-expressed in epithelial cancer cells and
stromal cells of the PhIP-induced mammary carcinomas, but was weak or not
apparent in normal mammary gland cells. The development of mammary carcinomas was
clearly suppressed by administration of nimesulide. The carcinoma incidence was
51% as compared to 71% for the control diet group. The average multiplicity of
carcinomas in the experimental diet group was 1.2 +/- 0.2 (P < 0.05),
significantly smaller than the control diet group value (2.6 +/- 0. 5). The size
of carcinomas was also clearly decreased; 1.1 +/- 0.4 cm(3) / rat in experimental
diet group (P < 0.05), 4.1 +/- 1.3 cm(3) / rat in the control diet group. The
results therefore provide evidence that the selective COX-2 inhibitor,
nimesulide, possesses chemopreventive activity against PhIP-induced mammary
carcinogenesis in rats.
PMID- 11011116
TI - Chemopreventive effect of curcumin on N-nitrosomethylbenzylamine-induced
esophageal carcinogenesis in rats.
AB - Modifying effects of curcumin (derived from the rhizome of Curcuma longa L.)
during the initiation or post-initiation phase of N-nitrosomethylbenzylamine
(NMBA)-induced esophageal carcinogenesis were investigated in male F344 rats.
Five-week-old rats were divided into 5 groups, and groups 1, 2 and 3 were given
intraperitoneal injections of NMBA (0.5 mg / kg body weight / injection 15 times)
for 5 weeks from 7 weeks old to induce esophageal neoplasms. Groups 2 and 3 were
fed the diet containing 500 ppm curcumin during the initiation and post
initiation phases, respectively. Group 4 was given the diet containing curcumin
throughout the experiment, and group 5 was kept on the basal diet alone and
served as an untreated control. Incidence and multiplicity of esophageal
neoplasms of group 1 (NMBA alone) were 66.7% and 0.83 +/- 0.70, respectively.
Those of groups 2 and 3 were significantly less than those of group 1 (39.3%,
0.46 +/- 0.64, P < 0.05; 33.3%, 0.36 +/- 0.56, P < 0.05, respectively).
Furthermore, the incidence and multiplicity of esophageal preneoplastic lesions
(moderate or severe epithelial dysplasia) of group 2 (57.1%, 0.61 +/- 0.57; 40%,
0.29 +/- 0.46) or 3 (56.7%, 0.67 +/- 0.66; 23.3%, 0.23 +/- 0.43) were less than
those of group 1 (100%, 1.67 +/- 0.70; 70.8%, 0.92 +/- 0.72) (P < 0.05). In this
experiment, feeding of curcumin significantly decreased the expression of cell
proliferation biomarkers (5-bromo-2'-deoxyuridine labeling index) in the non
lesional esophageal epithelium (P < 0.01). These findings indicate that curcumin
inhibits NMBA-induced esophageal carcinogenesis when given during the post
initiation as well as initiation phase. This inhibition may be related to
suppression of the increased cell proliferation induced by NMBA in the esophageal
epithelium.
PMID- 11011118
TI - Co-expression of thymidine phosphorylase and heme oxygenase-1 in macrophages in
human malignant vertical growth melanomas.
AB - Expression of thymidine phosphorylase (TP) is often associated with tumor
angiogenesis and / or prognosis in patients. Further, infiltration of macrophages
is closely correlated with the depth of tumor and angiogenesis in melanomas. In
this study, we examined the expression of TP and an activated macrophage-specific
enzyme, heme oxygenase-1 (HO-1), involved in malignancy in 22 cases with
melanomas. TP was strongly expressed not only in CD68-positive macrophages in and
around tumors, but also in S100 protein-positive melanoma cells, fibroblasts and
keratinocytes. By contrast, HO-1 was specifically expressed in macrophages, but
only slightly in melanoma cells and other cell types in the stroma of melanomas.
We thus observed apparent co-expression of TP and HO-1 in macrophages
infiltrating in the late stage of malignant melanomas. There appeared increasing
numbers of TP-positive cells in Clark level IV and V melanoma compared with Clark
level I (in situ) melanoma, and there was also a close correlation between
numbers of TP-positive cells and HO-1-positive cells. Both TP- and HO-1-positive
macrophages could be observed in the stroma in and around tumors in vertical
growth melanomas.
PMID- 11011117
TI - Lack of modifying effects of environmental estrogenic compounds on the
development of thyroid proliferative lesions in male rats pretreated with N-bis(2
hydroxypropyl)nitrosamine (DHPN).
AB - The modifying effects of various environmental estrogenic compounds on thyroid
carcinogenesis were investigated in a rodent two-stage carcinogenesis model. The
compounds examined were a soy isoflavone mixture (SI) and genistein (GEN) as
phytoestrogens, nonylphenol (NP) as a xenoestrogen, 3-chloro-4-(dichloromethyl)-5
hydroxy-2(5H)-furanone (MX) as a thyroid carcinogen and sulfadimethoxine (SDM) as
a known thyroid tumor promoter. Five-week-old male F344 rats were given a single
subcutaneous injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN; 2800 mg / kg,
body weight) or the vehicle alone. Starting one week thereafter, GEN (250 or 25
ppm in diet), SI (400 ppm in diet), NP (250 or 25 ppm in diet), MX (30 ppm, in
drinking water) or SDM (1000 ppm in drinking water) was administered for 12
weeks. Major organs including the thyroid, pituitary, liver, kidney, testis,
brain and pancreas were weighed and histopathological observation was performed.
Thyroid weights were significantly increased (P < 0.001) only in the SDM
treatment groups, especially with DHPN pretreatment. Kidney weights were slightly
increased in the NP or MX treatment groups, albeit without statistical
significance. Histopathologically, thyroid proliferative lesions were only
observed in the SDM alone or DHPN + SDM group with significant focal
hyperplasias, adenomas and adenocarcinomas limited to the combined treatment
case. There were no organ weight changes or histopathological lesions in the
major organs including the thyroid in the GEN, SI, NP, and MX treatment groups
regardless of DHPN pretreatment. Our results thus indicate that the weakly
estrogenic compounds GEN, SI and NP and the environmental rat thyroid carcinogen
MX do not exert any modifying effects on thyroid carcinogenesis in rats under the
present experimental conditions.
PMID- 11011119
TI - Regulation of granulocyte colony-stimulating factor and parathyroid hormone
related protein production in lung carcinoma cell line OKa-C-1.
AB - Previously we have established a clonal squamous cell carcinoma cell line OKa-C-1
derived from lung cancer of a patient with marked leukocytosis and hypercalcemia.
OKa-C-1 cells simultaneously produce granulocyte colony-stimulating factor (G
CSF) and parathyroid hormone-related protein (PTHrP) at the single cell level and
cause paraneoplastic syndromes in nude mice bearing the tumor. It is known that
the production of G-CSF and PTHrP is individually regulated by inflammatory
cytokines in various malignant cells. To investigate the common factors in the
regulation of G-CSF and PTHrP production in OKa-C-1 cells, we examined the
effects of some inflammatory agents [lipopolysaccharide (LPS), phorbol-12
myristate-13-acetate (PMA), tumor necrosis factor-alpha (TNF-alpha), interleukin
1 (IL-1) beta and IL-6] on G-CSF and PTHrP production, by means of enzyme-linked
immunosorbent assay (ELISA), immunoradiometric assay (IRMA) and quantitative
reverse transcription-polymerase chain reaction (RT-PCR). TNF-alpha or IL-1beta
induced both G-CSF and PTHrP production in the conditioned medium. TNF-alpha
synergized with IL-1beta to significantly increase G-CSF production. In addition,
TNF-alpha and IL-1beta strongly induced G-CSF mRNA with peaks at 2 and 6 h
respectively. Although PTHrP production was also strongly induced by TNF-a PTHrP
mRNA expression was more strongly induced by PMA than by TNF-alpha. Thus, TNF
alpha and IL-1beta could be common factors that individually and synergistically
regulate G-CSF and PTHrP production in OKa-C-1 cells. Moreover, G-CSF and PTHrP
production could be not only transcriptionally, but also posttranscriptionally
regulated by other factors.
PMID- 11011120
TI - Prognostic significance of occult bone marrow micrometastases of breast cancer
detected by quantitative polymerase chain reaction for cytokeratin 19 mRNA.
AB - Amplification of cytokeratin 19 (CK19) transcripts by reverse transcriptase
polymerase chain reaction (RT-PCR) has been shown to be a highly sensitive assay
for the detection of bone marrow micrometastases (BMM) of breast cancer, but
recent studies have demonstrated the occurrence of false-positive results due to
low-level, illegitimately transcribed CK19 in normal bone marrow tissue. One
approach to solve this problem is to develop a quantitative CK19 RT-PCR assay and
to introduce a cut-off value which can distinguish between illegitimate
expression and cancer-specific expression levels. In the present paper, we
describe a quantitative CK19 RT-PCR assay using a real-time automated PCR system.
The number of CK19 transcripts was normalized to that of GAPDH transcripts as an
internal control for quality and quantity of cDNA. The cut-off value for the
ratio of CK19 to GAPDH transcripts was set at 10(-4) since the ratio never
exceeded this value in the control bone marrow samples (n = 12). In total, 117
bone marrow aspirates from stage I - III patients with invasive breast cancers
were subjected to CK19 RT-PCR assay and immunocytological examination. Forty
(34.2%) were found to be BMM-positive by CK19 RT-PCR assay whereas only three
(2.6%) were found to be BMM-positive by immunocytology. Multivariate analysis has
shown that occult BMM detected by CK19 RT-PCR is a significant risk factor for
relapse, being independent of axillary lymph node metastases.
PMID- 11011121
TI - ICAM-1 (intercellular adhesion molecule-1) gene transfection inhibits lymph node
metastasis by human gastric cancer cells.
AB - Lymph node metastasis is one of the prognostic factors in gastric cancer. We have
previously reported that decreased intercellular adhesion molecule-1 (ICAM-1)
expression on cancer cells is associated with lymph node metastasis using a
gastric cancer cell. In this study, we transfected ICAM-1 gene into a gastric
cancer cell line, 2MLN, and analyzed the effect on lymph node metastasis in vitro
and in vivo. A significantly greater amount of peripheral blood mononuclear cells
(PBMC) adhered to ICAM-1 transfected 2MLN cells, 2MLN / ICAM cells, than to 2MLN
/ Vector cells. The lysis of 2MLN / ICAM cells by PBMC was significantly
increased compared with that of 2MLN / Vector cells. The tumor growth rate of
2MLN / ICAM cells was significantly decreased in vivo. Lymph node metastases
caused by 2MLN / ICAM cells were recognized as being fewer in number and smaller,
while many lymph node metastases were caused by 2MLN cells. Histologic findings
showed that leukocytes were heavily infiltrated in both the 2MLN / ICAM tumors
and metastatic lesions, while only a few leukocytes were observed in the lesions
associated with 2MLN cells. The above findings indicate that ICAM-1 gene
transduction could prove to be an effective gene therapy for lymph node
metastasis of gastric cancer.
PMID- 11011122
TI - Modulation of myogenic differentiation in a human rhabdomyosarcoma cell line by a
new derivative of 5-fluorouracil (QF-3602).
AB - The in vitro study of mechanisms involved in drug-induced maturation has made it
possible to use differentiation-based therapy in clinical practice. The goal of
this new therapy is the development of specific agents to induce cancer cells to
stop proliferating and express characteristics of normal cells. Recently, by
structural modifications of 5-fluorouracil (5-FU), we synthesized a new
pyrimidine acyclonucleoside-like compound, 1-?[3-(3-chloro-2-hydroxypropoxy)-1
methoxy]propyl?-5-fluorouracil (QF-3602), which showed in rhabdomyosarcoma cells
a low toxicity and time-dependent growth inhibition. In this work, we compared
the degree of myogenic differentiation of RD rhabdomyosarcoma (RMS) cells after
treatment with QF-3602 and 5-FU. Scanning and transmission electron microscopy
(SEM and TEM) and immunocytochemical analyses showed that QF-3602 induced the
appearance of myofilaments along the myotube-like giant RD cells, an increase in
fibronectin and a decrease in vimentin expression. In contrast, only minor
changes were observed with 5-FU. Moreover, polymerase chain reaction (PCR)
analyses showed that QF-3602 did not induce overexpression of the mdr 1 gene, a
resistance mechanism that frequently appears in classical cytotoxic therapy in
these tumors. Compounds obtained by structural modifications of 5-FU may be
useful in differentiation therapy as a new approach to the treatment of RMS.
PMID- 11011123
TI - p53 mutations in prostatic intraepithelial neoplasia and concurrent carcinoma:
analysis of laser capture microdissected specimens from non-transition and
transition zones.
AB - Prostatic intraepithelial neoplasia (PIN) is characterized by intraluminal
proliferation of epithelial cells and is divided into high-grade (HGPIN) and low
grade (LGPIN) lesions. HGPIN is regarded as the most likely precursor of
prostatic cancer (PCA). Microdissected DNA selectively extracted from paraffin
embedded sections of 27 cases with PCA were analyzed for p53 mutation in exons 5
8 by single-strand conformation polymorphism of polymerase chain reaction
amplified DNA fragments (PCR-SSCP) followed by direct sequencing. These patients
received total prostatectomy (27 cases). After a review of histologic sections,
DNA was extracted from 193 locations; 111 lesions from 27 cases with HGPIN (75
lesions from non-transition zone and 36 from transition zone), 55 lesions from 27
cases with PCA (30 lesions from non-transition zone and 25 from transition zone),
and 27 from 27 benign glands. Analysis revealed 27 mutations of the p53 gene in
24 lesions from 12 cases. Benign glands adjoining PIN and / or PCA had no
mutations. All mutations were point mutations: 17 missense, 7 silent, and 2
nonsense. Mutations were detected in 6 cases (22.2%) or 13 of 111 lesions (11.7%)
with HGPIN and 8 cases (29.6%) or 11 of 55 lesions (20.0%) with PCA. In a given
case, HGPIN and PCA lesions had different p53 mutations from each other,
suggesting multiclonal development of prostatic precancerous lesions. The
frequency of p53 mutation of PCA was significantly higher in the non-transition
zone (33.3%) than in the transition zone (4%), and higher in the stage T3 cases
(30.3%) than in the stage T2 cases (4.5%, 1 of 22 lesions) (both P < 0.05).
Frequency of p53 mutation of PIN in the non-transition zone (14.7%) was higher
than that in the transition zone (5.6%), although the difference was not
significant. The frequency rate of p53 mutation in HGPIN close to PCA ( = 2 mm)
was significantly higher (24%) than that in HGPIN lesions > 2 mm from PCA (3%).
All these findings indicate that the p53 gene mutations are involved in prostatic
carcinogenesis and explain why the non-transition zone is the predominant site of
PCA.
PMID- 11011124
TI - Relations of insulin resistance and serum concentrations of estradiol and sex
hormone-binding globulin to potential breast cancer risk factors.
AB - There is a hypothesis that hyperinsulinemia or insulin resistance may be a
mediator for breast cancer risk factors. On the other hand, some, but not all, of
the well-known risk factors of breast cancer have been associated with serum
estrogen concentrations. We assessed the relationships of potential breast cancer
risk factors to indicators of insulin resistance, fasting plasma insulin
concentration and homeostasis model assessment insulin resistance (HOMA-R), in 88
postmenopausal Japanese women. We also examined whether insulin resistance would
explain the association of breast cancer risk factors with serum estradiol and
sex hormone-binding globulin (SHBG). Information on potential breast cancer risk
factors, such as demographic characteristics, smoking and drinking habits, diet,
exercise, menstrual and reproductive factors, was obtained by self-administered
health questionnaire including a validated semiquantitative food frequency
questionnaire. Body mass index (BMI) was significantly correlated with the ratio
of estradiol to SHBG (Spearman r = 0.30, P = 0.0004), fasting plasma insulin (r =
0.45) and HOMA-R (r = 0.43, P = 0.0001) after controlling for age. The
correlations were still significant between BMI and estradiol / SHBG ratio (r =
0.21, P = 0.047) after controlling for fasting plasma insulin and between BMI and
fasting plasma insulin (r = 0.40, P = 0. 0001) as well as HOMA-R (r = 0.38, P =
0.0003) after controlling for estradiol / SHBG ratio. There is a possibility that
effect of BMI on breast cancer risk is mediated by both insulin resistance and
estrogen metabolism.
PMID- 11011136
TI - Metabolism of palmitic and docosahexaenoic acids in Reuber H35 hepatoma cells.
AB - In this work, we have modified the fatty acid composition of Reuber H35 hepatoma
cells by supplementation of the culture medium with a saturated (palmitic) or a
polyunsaturated (docosahexaenoic) acid. These fatty acids were incorporated into
total lipids and phospholipids of hepatoma cells. Palmitic acid readily increased
the percentage of its monounsaturated derivative (16:1 n-7). When both fatty
acids were supplemented at the same concentration, the percentage of
docosahexaenoic acid in the total lipids and phospholipids of Reuber H35 cells
increased more than that of palmitic acid. Although the levels of 16:0 increased,
the addition of docosahexaenoic acid to the culture medium decreased the
percentages of monoenoic acids. From our results, it can be concluded that
palmitic and docosahexaenoic acids modify the fatty acid composition of Reuber
H35 hepatoma cells. The profound changes induced by docosahexaenoic acid,
especially those in the phospholipid fraction, may be of great interest given the
main role of these components in the regulation of chemical and physical
properties of biological membranes and/or membrane systems.
PMID- 11011137
TI - Binding of an intrinsic ATPase inhibitor to the F(1)FoATPase in phosphorylating
conditions of yeast mitochondria.
AB - Yeast mitochondrial ATP synthase has three regulatory proteins; ATPase inhibitor,
9K protein, and 15K protein. A mutant yeast lacking these three regulatory
factors was constructed by gene disruption. Rates of ATP synthesis of both wild
type and the mutant yeast mitochondria decreased with decrease of respiration,
while their membrane potential was maintained at 170-160 mV under various
respiration rates. When mitochondrial respiration was blocked by antimycin A, the
membrane potential of both types of mitochondria was maintained at about 160 mV
by ATP hydrolysis. ATP hydrolyzing activity of F(1)FoATPase solubilized from
normal mitochondria decreased in proportion to the rate of ATP synthesis, while
the activity of the mutant F(1)FoATPase was constant regardless of changes in the
rate of phosphorylation. These observations strongly suggest that F(1)FoATPase in
the phosphorylating mitochondria is a mixture of two types of enzyme,
phosphorylating and non-phosphorylating enzymes, whose ratio is determined by the
rate of respiration and that the ATPase inhibitor binds preferentially to the non
phosphorylating enzyme.
PMID- 11011138
TI - EmPLiCS: an empirical approach for structure-based design of natural peptide
drugs.
AB - The computer implementation of a peptide drug-design strategy has been developed.
The system is named EmPLiCS (Empirical Peptide Ligand Construction System)
according to the strategy of the system, which searches for peptide-ligand
structures by referring to empirical rules that are derived from known protein 3D
structures. The system was tested on several known peptide-protein complexes. The
results demonstrated the ability of this system to detect key residues of
peptides that are crucial for interaction with their specific proteins. The
system also showed the ability to detect the main chain trace of these peptides.
Some of the main chain atoms were detected even though the complete primary
structures were not reproduced, suggesting that main chain structure is important
in peptide-protein recognition. The results of the present study demonstrated
that the empirical rules-based system can generate significant information for
use in the design of natural peptide drugs.
PMID- 11011140
TI - Enhanced thermostability of the single-Cys mutant subtilisin E under oxidizing
conditions.
AB - We obtained enhanced thermostability by replacing Ser161 with Cys in subtilisin E
from Bacillus subtilis, a cysteine-free alkaline serine protease. The Ser161Cys
mutant subtilisin E was purified from the culture supernatant of the recombinant
B. subtilis in an oxidizing environment. SDS-polyacrylamide gel electrophoresis
and mass spectrometry under oxidizing conditions indicated that the mutant enzyme
in part formed an oligomeric protein, which may contain an intermolecular
disulfide bond between two surface Cys residues at position 161. Further, no free
sulfhydryl groups were detected in the mutant enzyme, suggesting the sulfhydryl
modification in a monomeric form under oxidizing conditions. The Ser161Cys mutant
enzyme showed a catalytic efficiency equivalent to that of the wild-type enzyme.
The half-life of thermal inactivation of the mutant was found to be 2-4 times
longer than that of the wild-type enzyme. The optimum temperature of the mutant
was 55 degrees C, which was 5 degrees C higher than that of the wild-type enzyme.
Under reducing conditions, however, the characteristics of the mutant enzyme
reverted to those of the wild-type enzyme. Similar results were obtained for
another Cys mutant as to position 194 (wild-type, Ser), which is the same surface
residue as Ser161. Possible reasons for the enhanced thermostability of the
single-Cys mutant subtilisins E under oxidizing conditions are discussed in terms
of two different mechanisms.
PMID- 11011139
TI - Genetic characterization of rbt mutants that enhance basal transcription from
core promoters in Saccharomyces cerevisiae.
AB - While this Saccharomyces cerevisiae SIN4 gene product is a component of a
mediator complex associated with RNA polymerase II, various studies suggest the
involvement of Sin4 in the alteration of higher-order chromatin structure. Our
previous analysis of a sin4 mutant suggested that the mechanisms of
transcriptional repression by Sin4 (mediator) and the Tup1-Ssn6 complex (general
repressor) are different. To elucidate the way in which these two repression
systems are interrelated, we isolated mutants that exhibit enhanced transcription
of a reporter gene harboring the upstream activation sequence (UAS), but still
are subject to Tup1-Ssn6-mediated repression. Besides sin4, rgr1, tup1, and ssn6
mutants, we also obtained new mutants that enhance basal transcription even from
a core promoter without UAS. Such mutants, designated rbt for regulator of basal
transcription, can be classified into at least six complementation groups, i.e.,
four single (rbt1 to rbt4) and two apparently double (rbt5 rbt6 and rbt7 rbt8)
mutations. The phenotype of rbt mutants is dependent on the TATA box and not
specific to the integration site or kind of core promoter. No significant
difference in micrococcal nuclease (MNase) accessibility to the core promoter of
test genes was observed between rbt mutants and the wild-type strain, indicating
that the higher-order chromatin structure of the core promoter region is not
significantly altered in these mutants. The rbt1 to rbt4 mutations are suppressed
by the Dgal11 mutation as in the case of the sin4 mutation, but give rise to a
different profile from the sin4 mutation with regard to the activity of some of
the promoters. From these observations, we suggest that RBT gene product(s) could
be novel mediators that act with or in close association with Sin4 but have a
function distinct from that of Sin4. Moreover, the fact that rbt mutations
nullify Tup1-Ssn6 general repressor-mediated repression is consistent with the
idea that the mechanisms of Rbt (mediator)- and Tup1-Ssn6 (general repressor)
mediated repression are interconnected but substantially different.
PMID- 11011141
TI - The role of structural intersubunit microheterogeneity in the regulation of the
activity in hysteresis of ribulose 1, 5-bisphosphate carboxylase/oxygenase.
AB - Many enzymes are composed of subunits with the identical primary structure. It
has been believed that the protein structure of these subunits is the same.
Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) comprises eight large
subunits with the identical amino acid sequence and eight small subunits.
Rotation of the side chains of the lysine residues, Lys-21 and Lys-305, in each
of the eight large subunits in spinach RuBisCO in two ways produces
microheterogeneity among the subunits. These structures are stabilized through
hydrogen bonds by water molecules incorporated into the large subunits. This may
cause different effects upon catalysis and a hysteretic, time-dependent decrease
in activity in spinach RuBisCO. Changing the amino acid residues corresponding to
Lys-21 and Lys-305 in non-hysteretic Chromatium vinosum RuBisCO to lysine induces
hysteresis and increases the catalytic activity from 8.8 to 15.8 per site per
second. This rate is approximately five times higher than that of the higher
plant enzyme.
PMID- 11011142
TI - Mouse T-cell antigen rt6.1 has thiol-dependent NAD glycohydrolase activity.
AB - Mouse Rt6.1 and Rt6.2, homologues of rat T-cell RT6 antigens, catalyze arginine
specific ADP-ribosylation. Without an added ADP-ribose acceptor, Rt6.2 shows NAD
glycohydrolase (NADase) activity. However, Rt6.1 has been reported to be
primarily an ADP-ribosyltransferase, but not an NADase. In the present study, we
obtained evidence that recombinant Rt6.1 catalyzes NAD glycohydrolysis but only
in the presence of DTT. The NADase activity of Rt6.1 observed in the presence of
DTT was completely inhibited by N-ethylmaleimide (NEM). Native Rt6.1 antigen,
immunoprecipitated from BALB/c mouse splenocytes with polyclonal antibodies
generated against recombinant RT6.1, also exhibited NADase activity in the
presence of DTT. Compared with Rt6.2, Rt6.1 has two extra cysteine residues at
positions 80 and 201. When Cys-80 and Cys-201 in Rt6.1 were replaced with the
corresponding residues of Rt6.2, serine and phenylalanine, respectively, Rt6.1
catalyzed the NADase reaction even in the absence of DTT. Conversely, replacing
Ser-80 and Phe-201 in Rt6.2 with cysteines, as in Rt6.1, converted the thiol
independent Rt6.2 NADase to a thiol-dependent enzyme. Kinetic study of the NADase
reaction revealed that the affinity of Rt6.1 for NAD and the rate of catalysis
increased in the presence of DTT. Moreover, the NADase activity of Rt6.1
expressed on COS-7 cells was stimulated by culture supernatant from activated
mouse macrophages, even in the absence of DTT. From these observations, we
conclude that t!he Rt6.1 antigen has thiol-dependent NADase activity, and that
Cys-80 and Cys-201 confer thiol sensitivity to Rt6.1 NADase. Our results also
suggest that upon the interaction of T-cells expressing Rt6.1 with activated
macrophages, the NADase activity of the antigen will be stimulated.
PMID- 11011144
TI - Autoantibody activity of IgG rheumatoid factor increases with decreasing levels
of galactosylation and sialylation.
AB - The occurrence of N-linked oligosaccharides lacking galactose is significantly
higher than normal in serum IgG of patients with rheumatoid arthritis (RA) in
whom rheumatoid factor (RF), an autoantibody against autologous IgG, has been
detected. In the present study, IgGs with and without RF activity (IgGRF and non
RF IgG, respectively) were prepared from sera of RA patients, and their
oligosaccharide structures were characterized in order to investigate the
relationship between RF activity and glycosylation. Three IgGRF fractions and a
non-RF IgG fraction were obtained based on their ability to bind to an IgG
Sepharose column. The specific RF activity, as measured by immunoassays, was
highest in the IgGRF fraction, which bound most avidly to the IgG-Sepharose. When
the oligosaccharides were released by hydrazinolysis, and analyzed by MALDI-TOF
mass spectrometry and HPLC, in combination with sequential exoglycosidase
treatment, all the IgG samples were found to contain a series of biantennary
complex-type oligosaccharides. The incidence of galactose-free oligosaccharides
was significantly higher in both IgGRFs and non-RF IgG from RA patients compared
with IgG from healthy individuals. In all IgGRFs, the levels of sialylation and
galactosylation were lower than those in non-RF IgG from RA patients; the
sialylation of non-RF IgG was the same as that of IgG from healthy individuals.
In addition, the decreases in galactosylation and sialylation of oligosaccharides
in IgGRF correlated well with the increase in RF activity. These findings could
contribute to our understanding of the mechanisms of IgG-IgG complex formation
and the pathogenicity of these complexes in RA patients.
PMID- 11011143
TI - Kinetic basis for the donor nucleotide-sugar specificity of beta1, 4-N
acetylglucosaminyltransferase III.
AB - The kinetic basis of the donor substrate specificity of beta1, 4-N
acetylglucosaminyltransferase III (GnT-III) was investigated using a purified
recombinant enzyme. The enzyme also transfers GalNAc and Glc moieties from their
respective UDP-sugars to an acceptor at rates of 0.1-0.2% of that for GlcNAc, but
Gal is not transferred at a detectable rate. Kinetic analyses revealed that these
inefficient transfers, which are associated with the specificity of the enzyme,
are due to the much lower V(max) values, whereas the K(m) values for UDP-GalNAc
and UDP-Glc differ only slightly from that for UDP-GlcNAc. It was also found that
various other nucleotide-Glc derivatives bind to the enzyme with comparable
affinities to those of UDP-GlcNAc and UDP-Glc, although the derivatives do not
serve as glycosyl donors. Thus, GnT-III does not appear to distinguish UDP-GlcNAc
from other structurally similar nucleotide-sugars by specific binding in the
ground state. These findings suggest that the specificity of GnT-III toward the
nucleotide-sugar is determined during the catalytic process. This type of
specificity may be efficient in preventing a possible mistransfer when other
nucleotide-sugars are present in excess over the true donor.
PMID- 11011145
TI - Monoclonal antibodies recognizing surface residues of the beta subunit of
Escherichia coli F(1) ATPase: functional importance of the epitope residues.
AB - Two monoclonal antibodies, beta 208 and beta 210, against the beta subunit of the
F(1) ATPase from Escherichia coli reacted with an intact beta subunit and also a
peptide corresponding to a portion of beta between residues 1 and 145. Mutations
at Ala-1, Val-15, Glu-16, Phe-17, Leu-29, Gly-65, or Leu-66, and His-110 or Arg
111 for beta 210 and beta 208, respectively, caused decreased antibody binding to
beta, suggesting that these residues form the epitopes and are thought to lie
close together on the surface of the beta subunit. The topological locations of
the corresponding residues in the atomic structure of the bovine beta subunit
agree well with these expectations, except for Ala-1 and Leu-29. beta 210 binds
to two beta strands including the epitope residues that are 50 residues apart,
indicating that this antibody recognizes the tertiary structure of the N-terminal
end region. Mutations in the epitope residues of beta 210 do not affect the F(1)
ATPase activity, suggesting that surfaces of the two beta strands in the amino
terminal end region are not functionally essential. To analyze the functional
importance around His-110 recognized by beta 208 we introduced site specific
mutations at residues His-110 and Ile-109. Ile-109 to Ala or Arg, and His-110 to
Ala or Asp caused defective assembly of F(1). However, the His-110 to Arg
mutation had no effect on molecular assembly, suggesting that Ile-109 and His
110, especially the positive charge of His-110 are essential for the assembly of
F(1). The His-110 to Arg mutation caused a large decrease in F(1)-ATPase
activity, suggesting that a subtle change in the topological arrangement of the
positive charge of His-110 located on the surface of beta plays an important role
in the catalytic mechanism of the F(1)-ATPase.
PMID- 11011146
TI - Calcium-dependent and -independent hetero-oligomerization in the synaptotagmin
family.
AB - Synaptotagmins constitute a family of membrane proteins that are characterized by
one transmembrane region and two C2 domains. Recent genetic and biochemical
studies have indicated that oligomerization of synaptotagmin (Syt) I is important
for expression of function during exocytosis of synaptic vesicles. However,
little is known about hetero-oligomerization in the synaptotagmin family. In this
study, we showed that the synaptotagmin family is a type I membrane protein
(N(lumen)/C(cytoplasm)) by introducing an artificial N-glycosylation site at the
N-terminal domain, and systematically examined all the possible combinations of
hetero-oligomerization among synaptotagmin family proteins (Syts I-XI). We
classified the synaptotagmin family into four distinct groups based on
differences in Ca(2+)-dependent and -independent oligomerization activity. Group
A Syts (III, V, VI, and X) form strong homo- and hetero-oligomers by disulfide
bonds at an N-terminal cysteine motif irrespective of the presence of Ca(2+)
[Fukuda, M., Kanno, E., and Mikoshiba, K. (1999) J. Biol. Chem. 274, 31421
31427]. Group B Syts (I, II, VIII, and XI) show moderate homo-oligomerization
irrespective of the presence of Ca(2+). Group C synaptotagmins are characterized
by weak Ca(2+)-dependent (Syts IX) or no homo-oligomerization activity (Syt IV).
Syt VII (Group D) has unique Ca(2+)-dependent homo-oligomerization properties
with EC(50) values of about 150 microM Ca(2+) [Fukuda, M., and Mikoshiba, K.
(2000) J. Biol. Chem. 275, 28180-28185]. Syts IV, VIII, and XI did not show any
apparent hetero-oligomerization activity, but some sets of synaptotagmin isoforms
can hetero-oligomerize in a Ca(2+)-dependent and/or -independent manner. Our data
suggest that Ca(2+)-dependent and -independent hetero-oligomerization of
synaptotagmins may create a variety of Ca(2+)-sensors.
PMID- 11011147
TI - Nitric oxide inactivates glyoxalase I in cooperation with glutathione.
AB - We previously found that glyoxalase I (Glo I) is inactivated upon exposure of
human endothelial cells to extracellular nitric oxide (NO), and this event
correlates with an increase in its pI on two-dimensional gels. In this study, we
demonstrate that NO can modulate Glo I activity in cooperation with cellular
glutathione (GSH). Severe depletion of intracellular GSH prevents the
inactivation of Glo I in response to NO, although such depletion enhances the
inactivation of glyceraldehyde-3-phosphate dehydrogenase (G3PDH), a well-known
enzyme susceptible to NO-induced oxidation. S-Nitrosoglutathione (GSNO), an
adduct of GSH and NO, lowers the activity of purified human Glo I, while S
nitrosocysteine (CysNO) inactivates the enzyme only in the presence of GSH. This
indicates that a dysfunction in Glo I would require the formation of GSNO in
situ. Competitive inhibitors of Glo I, S-(4-bromobenzyl)glutathione and its
membrane-permeating form, completely abolish the NO action in vitro and inside
cells, respectively. Taken together, these results reveal that Glo I can interact
directly with GSNO, and that the interaction converts Glo I into an inactive
form. Moreover, the data suggest that the substrate recognition site of Glo I
might be involved in the interaction with GSNO.
PMID- 11011148
TI - Synthesis and characterization of the spore proteins of Bacillus subtilis YdhD,
YkuD, and YkvP, which carry a motif conserved among cell wall binding proteins.
AB - We have previously reported that YaaH and YrbA are spore proteins of Bacillus
subtilis that are required for spore resistance and/or germination and that they
have a motif conserved among so-called cell wall binding proteins [Kodama et al.
(1999) J. Bacteriol. 181, 4584-4591, Takamatsu et al. (1999) J. Bacteriol. 181,
4986-4994]. In this study, we analyzed the expression of ydhD, ykuD, and ykvP
genes, which encode putative proteins containing the same motif. Transcription of
ydhD was dependent on SigE, and the mRNA was detectable from 2 h after the
cessation of logarithmic growth (T(2) of sporulation). ykuD was transcribed by
SigK RNA polymerase from T(4) of sporulation. Both SigK and GerE were essential
for ykvP expression, and this gene was transcribed from T(5) of sporulation.
Inactivation of these genes by insertion of an erythromycin resistance gene did
not affect vegetative growth, spore resistance to heat, chloroform, and lysozyme,
or spore germination in the presence of L-alanine or in a mixture of L
asparagine, D-glucose, D-fructose, and potassium chloride. The His tag fusions of
YdhD, YkuD, and YkvP downstream of their natural promoter regions were introduced
into a multicopy plasmid. These fusion proteins were produced during sporulation
in B. subtilis transformants and were detected in mature spores, indicating that
YdhD, YkuD, and YkvP are all proteins intrinsic to spores. Excessive YkuD and
YkvP in the sporulating cells did not affect spore resistance or germination. The
cells producing excessive YdhD also did not show impaired spore resistance, but
their germination properties were changed: the spores revealed reduced response
to L-alanine and some of them germinated even without germinants. Escherichia
coli b-lactamase, whose signal sequence had been genetically replaced by the cell
wall binding motif of YaaH, was produced in sporulating cells, and Western blot
analysis indicated that the fused protein was assembled into spores. We speculate
that the conserved motif functions as a kind of signal sequence involved in
assembly of these proteins on forespores.
PMID- 11011149
TI - Multiple actin-related proteins of Saccharomyces cerevisiae are present in the
nucleus.
AB - An increasing number of actin-related proteins (Arps), which share the basal
structure with skeletal actin but possess distinct functions, have been found in
a wide variety of organisms. Individual Arps of Saccharomyces cerevisiae were
classified into Arps 1-10 based on the relatedness of their sequences and
functions, where Arp1 is the most similar to actin, and Arp10 is the least
similar. While Arps 1-3 and their orthologs in other organisms are localized
exclusively in the cytoplasm, Arp4 (also known as Act3) is localized in the
nucleus and is involved in transcriptional regulation. Here we examined the more
divergent Arps for possible nuclear functions. We show that Arps 5-9 are
localized in the nucleus, but Arp10 is not. The nuclear export signals identified
in actin are well conserved in the cytoplasmic Arps, Arps 1-3, but less conserved
in the nuclear Arps. Gel filtration chromatography experiments show that the
nuclear Arps are larger than monomer in size and thus are present in multi
protein complexes. Since nuclear protein complexes containing Arps are found to
be responsible for histone acetylation and chromatin remodeling, it is suggested
that most of the divergent Arps are involved in the !transcriptional regulation
through chromatin modulation.
PMID- 11011150
TI - Substrate recognition mechanism of prolyl aminopeptidase from Serratia
marcescens.
AB - Molecular cloning of the gene and the crystal structure of the prolyl
aminopeptidase [EC 3.4.11.5] from Serratia marcescens have been studied by us [J.
Biochem. 122, 601-605 (1997); ibid. 126, 559-565 (1999)]. Through these studies,
Phe139, Tyr149, Glu204, and Arg136 were estimated to be concerned with substrate
recognition. To elucidate the details of the mechanism for the substrate
specificity, the site-directed mutagenesis method was applied. The F139A mutant
showed an 80-fold decrease in catalytic efficiency (k(cat)/K(m)), but the Y149A
mutant did not show a significant change in catalytic efficiency. The catalytic
efficiency of the E204Q mutant was about 4% of that of the wild type. The
peptidase activity of the mutant (R136A) was markedly decreased, however,
arylamidase activity with Pyr-bNA was retained as in the wild-enzyme. From these
results, it was clarified that the pyrrolidine ring and the amino group of
proline at the S1 site were recognized by Phe139 and Glu204, respectively. P1' of
a substrate was recognized by Arg136. On the other hand, the enzyme had two
cysteine residues. Mutants C74A and C271A were inhibited by PCMB, but the double
mutated enzyme (C74/271A) was resistant to it.
PMID- 11011151
TI - Stereochemistry of the transamination reaction catalyzed by aminodeoxychorismate
lyase from Escherichia coli: close relationship between fold type and
stereochemistry.
AB - Aminodeoxychorismate lyase is a pyridoxal 5'-phosphate-dependent enzyme that
converts 4-aminodeoxychorismate to pyruvate and p-aminobenzoate, a precursor of
folic acid in bacteria. The enzyme exhibits significant sequence similarity to
two aminotransferases, D-amino acid aminotransferase and branched-chain L-amino
acid aminotransferase. In the present study, we have found that
aminodeoxychorismate lyase catalyzes the transamination between D-alanine and
pyridoxal phosphate to produce pyruvate and pyridoxamine phosphate. L-Alanine and
other D- and L-amino acids tested were inert as substrates of transamination. The
pro-R hydrogen of C4' of pyridoxamine phosphate was stereospecifically abstracted
during the reverse half transamination from pyridoxamine phosphate to pyruvate.
Aminodeoxychorismate lyase is identical to D-amino acid aminotransferase and
branched-chain L-amino acid aminotransferase in the stereospecificity of the
hydrogen abstraction, and differs from all other pyridoxal enzymes that catalyze
pro-S hydrogen transfer. Aminodeoxychorismate lyase is the first example of a
lyase that catalyzes pro-R-specific hydrogen abstraction. The result is
consistent with recent X-ray crystallographic findings showing that the
topological relationships between the cofactor and the catalytic residue for
hydrogen abstraction are conserved among aminodeoxychorismate lyase, D-amino acid
aminotransferase and branched-chain L-amino acid aminotransferase [Nakai, T.,
Mizutani, H., Miyahara, I., Hirotsu, K., Takeda, S., Jhee, K.-H., Yoshimura, T.,
and Esaki, N. (2000) J. Biochem. 128, 29-38].
PMID- 11011152
TI - Solution structure of myosin-ADP-MgFn ternary complex by fluorescent probes and
small-angle synchrotron X-ray scattering.
AB - In the presence of excess amounts of fluorine, a physiological divalent cation,
magnesium (Mg(2+)), forms a novel phosphate analogue, magnesium fluoride (MgFn).
Park et al. [Biochim. Biophys. Acta 1430, 127-140 (1999)] previously demonstrated
that MgADP. MgFn forms a complex with myosin subfragment-1 (S-1), and the S
1.ADP. MgFn ternary complex mimics a transient state in the activity cycle of
ATPase. In the present study, localized conformations in the regions of highly
reactive cysteine and lysine residues, Cys 707 (SH1), Cys 697 (SH2), and Lys 83
(RLR), which change their conformations markedly during ATP hydrolysis, were
studied using fluorescent probes and chemical modification. The global shape of
the complex was also studied using small angle X-ray solution scattering and
compared it with other previously reported myosin.ADP. fluorometal ternary
complexes. The results suggest that the overall conformation and localized
functional regions of the complex are quite similar to those in the presence of
ATP, indicating that the complex mimics the M(**).ADP.P(i) steady state.
PMID- 11011153
TI - Conformational changes in the unique loops bordering the ATP binding cleft of
skeletal muscle myosin mediate energy transduction.
AB - Myosin has three highly-conserved, unique loops [B (320-327), M (677-689), and N
(127-136)] at the entrance of the ATP binding cleft, and we previously showed
that the effects of actin are mediated by a conformational change in loop M
[Maruta and Homma (1998) J. Biochem. 124, 528-533]. In the present study, loops M
and N were photolabeled respectively with fluorescent probes Mant-8-N(3)-ADP and
Mant-2-N(3)-ADP in order to study conformational changes in the loops related to
energy transduction. The effect of actin on the conformation of loop N was
examined by analyzing fluorescence polarization and acrylamide quenching; the
results were then compared with those previously reported for loop M. In contrast
to loop M, the fluorescence polarization and the value of K(sv) of the Mant
groups crosslinked to loop N were slightly affected by actin binding. To study
conformational changes in loops M and N during the ATPase cycle, FRET was
analyzed using TNP-ADP.BeFn and TNP-ADP. AlF(4)(-) as FRET acceptors of Mant
fluorescence. The resultant estimated distances between loop M and the active
site differed for the Mant-S1.TNP-ADP.BeFn and Mant-S1.TNP-ADP.AlF(4)(-)
complexes, whereas the distances between loop N and the active site differed
slightly. These findings indicate that the conformation of loop M changes during
the ATPase cycle, suggesting that Loop M acts as a signal transducer mediating
communication between the ATP- and actin-binding sites. Loop N, by contrast, is
not significantly flexible.
PMID- 11011154
TI - Fibrinogen binds to integrin alpha(5)beta(1) via the carboxyl-terminal RGD site
of the Aalpha-chain.
AB - Fibrinogen interactions with vascular endothelial cells are implicated in various
physiological and pathophysiological events, including angiogenesis and wound
healing. We have shown previously that integrin alpha(5)beta(1) is a fibrinogen
receptor on endothelial cells [Suehiro, K., Gailit, J., and Plow, E.F. (1997) J.
Biol. Chem. 272, 5360-5366]. In the present study, we have characterized
fibrinogen interactions with purified alpha(5)beta(1) and have identified the
recognition sequence in fibrinogen for alpha(5)beta(1). The binding of fibrinogen
to immobilized alpha(5)beta(1) was selectively supported by Mn(2+). Fibrinogen
bound to purified alpha(5)beta(1) in a time-dependent, specific, and saturable
manner in the presence of Mn(2+), and the binding was blocked completely by Arg
Gly-Asp (RGD)-containing peptides and by anti-alpha(5) and anti-alpha(5)beta(1)
monoclonal antibodies. A monoclonal antibody directed to the C-terminal RGD
sequence at Aalpha572-574 significantly inhibited the binding of fibrinogen to
alpha(5)beta(1), whereas monoclonal antibodies directed to either the N-terminal
RGD sequence at Aalpha95-97 or the C-terminus of the gamma-chain did not.
Furthermore, substituting RGE for RGD at position Aalpha95-97 in recombinant
fibrinogen had a minimal effect on binding, whereas substituting RGE for RGD at
position Aalpha572-574 decreased binding by 90%. These results demonstrate that
the C-terminal RGD sequence at Aalpha572-574 is required for the interaction of
fibrinogen with alpha(5)beta(1).
PMID- 11011156
TI - [The association of French-speaking dermatologists].
PMID- 11011155
TI - A half-type ABC transporter TAPL is highly conserved between rodent and man, and
the human gene is not responsive to interferon-gamma in contrast to TAP1 and
TAP2.
AB - TAPL is a half-type ABC transporter with sequence similarity to TAP1 and TAP2
that is transcribed in various rat tissues [Yamaguchi, Y., Kasano, M., Terada,
T., Sato, R., and Maeda, M. (1999) FEBS Lett. 457, 231-236]. Primary structures
of the human and mouse orthologous counterparts were deduced from cDNAs cloned by
means of polymerase chain reaction, and they were compared with that of the rat.
The mammalian TAPLs (rat, mouse, and human) are highly conserved, since about 95%
of the amino acid residues are identical between rodents and man. Phylogenetic
analysis demonstrated that the evolutional rate of TAPL is much slower than those
of TAP1 and TAP2, although TAPL could have diverged from an ancestor of TAP1 or
that of TAP1 and TAP2. The TAPL-GFP fusion protein transiently expressed in Cos-1
cells was co-localized with PDI, suggesting that TAPL is inserted into
endoplasmic reticulum membrane. The conservation of the peptide-binding motifs of
TAP proteins in TAPL raises the possibility that the TAPL might be a peptide
transporter. The gene for human TAPL is assigned to chromosome 12q24.31-q24.32,
while those for TAP1 and TAP2 are located at the MHC locus of chromosome 6p21.!3.
Furthermore, the transcription of TAPL gene is not responsive to interferon
gamma, in contrast to TAP1 and TAP2. These results indicate that the gene
regulation of TAPL is different from those of TAP1 and TAP2.
PMID- 11011157
TI - [Should immunosuppressors be used for the treatment of atopic dermatitis?].
PMID- 11011158
TI - [Bioavailability evaluation of dermocorticoids using differential infrared
thermography].
AB - INTRODUCTION: Differential infrared thermography, proposed in this paper, is a
technique based on direct observations of infrared radiations emitted by the
skin. The evolution of cutaneous temperature caused by the application of
dermocorticoids on healthy skin demonstrates their pharmaco-dynamic properties.
MATERIALS AND METHODS: The cutaneous thermal image was recorded in real time.
Image processing using subtraction function readily provided differential
infrared thermographic analysis of the effects. Four activity classes of
dermocorticoids had been applied on healthy skin. A test immediately carried out
after dermocorticoid application on skin without occlusion and the classical skin
blanching-test have been performed. RESULTS: Temperature differences between the
dermocorticoids were detected within the first three hours after the application
on the skin without occlusion. The dermocorticoid class II cream formulation
under study induced a decrease in temperature more pronounced than the others
dermocorticoids. The skin-blanching effect was more noticeable for
dermocorticoids class I and II and it was not detected for class IV. DISCUSSION:
Subtraction thermograms provide a means of differential imaging. Evolutive
temperature differences subsequent to unique application without dermocorticoid
occlusion are evidenced during a short duration (the first three hours). This may
correspond to efficacy differences while classical tests of vasoconstriction
analyse the cutaneous blanching induced after the 6th hour. Concerning the skin
blanching effect, results of this first investigation are not sufficient for a
precise qualitative and quantitative interpretation. The main interest of
differential infrared thermography is to be quantitative, without contact,
continuous in real time. Differential infrared thermography is more sensitive
than classical thermography. It allowed an objective evolution survey for
dermocorticoids.
PMID- 11011159
TI - [Herpetiform ulceration: 5 cases].
AB - BACKGROUND: Mouth ulcers are frequently observed, mostly caused by trauma and
aphthae. We report five cases of herpetiform ulceration, a rare clinical form of
aphthae often mistaken for herpetic stomatitis because of the similar clinical
presentation. CASE REPORTS: All patients were men with late age at onset (44.8
years). All had numerous tiny very painful ulcers covering all parts of the oral
cavity. Consequences were sometimes severe (weight loss and general weakness in
two patients, requiring hospitalization in one). Diverse clinical courses were
observed (from no recurrence to monthly recurrence). Systemic steroids resulted
in dramatic improvement in two patients, colchicine prevented recurrences in
three of them. DISCUSSION: These observations illustrate well this rare disease:
herpetiform ulceration. We found oral corticosteroids provide effective cure and
observed the preventive action of colchicine. Both findings should be confirmed
in larger series.
PMID- 11011160
TI - [Gonorrhea in sexually abused young girls in Lome (Togo)].
AB - INTRODUCTION: Sexually transmitted diseases due to a sexual abuse cause are
rarely documented in black Africa. The purpose of this study was to demonstrate
the existence of sexual abuse in young girls with gonorrhea observed in Lome
(Togo). PATIENTS AND METHODS: A cross-sectional study was conducted to document
cases of sexually transmitted diseases diagnosed in young children (0 to 11 years
of age) seen at the dermato-venereology unit of the Lome teaching hospital over a
20 month period. Syphilis serology (TPHA-VDRL) and HIV serology were carried out
for all children with sexually transmitted disease and repeated after two weeks
for TPHA-VDRL, and three months for HIV serology in children who had been
sexually abused. RESULTS: During this period, 13 of 33 cases of sexually
transmitted diseases diagnosed in young children were gonorrhea (mean age 7.2 +/-
2.7 years). It was due to sexual abuse in 12 cases (all in young girls). The
abuser was a domestic employee in the child's home (n =3), a member of the
child's family (n =7), an educator (n =1), a neighbor (n =1). Mean age of the
alleged authors of sexual abuse was 25.7 +/- 5.5 years. Syphilis serology was
negative, but one case of HIV infection in a 10-year-old girl was observed with
identification of the contaminator. CONCLUSION: The results of this study confirm
that sexual abuse in children is not an uncommon occurrence in black Africa and
that it often leads to gonorrhea. The classic consequences of such abuse are
aggravated by the high prevalence of HIV infection observed in the majority of
the countries in black Africa.
PMID- 11011161
TI - [Eosinophilic ulceration of the tongue].
AB - BACKGROUND: Eosinophilic ulceration of the tongue is a classic condition little
reported in the literature. We describe a case in a patient taking nicorandil.
CASE REPORT: An 84-year-old patient consulted for an ulceration of the tongue
which had progressed for 5 months. The ulcer was very painful and the patient had
lost 2.5 kg. The patient had been taking nicorandil at the dose of 10 mg/d for a
year. Biopsies of the tongue ulcer confirmed the diagnosis of eosinophilic
ulceration. Immunohistochemistry determined predominantly T-cell infiltration.
Search for Epstein-Barr virus was negative. The ulcer completely regressed within
one month without withdrawal of nicorandil. DISCUSSION: This was a typical case
of eosinophilic ulceration of the tongue, both from the point of view of the
clinical expression and the histological findings. A nicorandil-induced ulcer was
ruled out on clinical (low daily dose, delay to onset) and histological arguments
as well as the spontaneous regression without drug withdrawal. Nicorandil may
have played a role in the abnormally long duration of the ulceration.
PMID- 11011162
TI - [Localized bullous pemphigoid induced by thermal burn].
AB - BACKGROUND: Induced bullous pemphigoid is known to be triggered by drugs and some
physical agents. Six cases of bullous pemphigoid induced by thermal burns have
been reported since 1991. CASE REPORT: We observed a bullous eruption around
thermal burns of the left leg in a 89 year-old woman. Bullous pemphigoid was
diagnosed by histological and immunohistochemical findings with a sub-epidermal
blister and linear IgG and C3 deposition at the dermal-epidermal junction.
Indirect immunofluorescence was negative. The eruption rapidly resolved with
topical steroids. DISCUSSION: We describe a bullous pemphigoid induced by a
thermal burn. This case is original because the eruption was localized only
around the site of the burn and healed with topical steroids. In the literature,
there are 6 other cases reported but only one localized. We discuss the
hypothesis of asymptomatic bullous pemphigoid exacerbated by presentation of
bullous pemphigoid antigen by thermal burns or self immunization against antigens
altered by burns.
PMID- 11011163
TI - [Granuloma annulare of the photoexposed areas in two liver transplant
recipients].
AB - BACKGROUND: We report two cases of generalized granuloma annulare occurring in
photoexposed areas in two liver transplant recipients. CASE REPORTS: Case 1 was a
65-year-old man who had undergone liver transplantation in 1992. He was given
immunosuppressive and antihypertensive therapy. Within 18 months of
transplantation, he developed a confluent rash with maculae on sun-exposed areas
(neck opening, nape, arms) and sparing the undershirt area. Clinical examination
was normal. Skin biopsy revealed a palissade infiltrate located in the middle and
upper derma, suggestive of granuloma annulare, with elastophagocytosis patterns
(orcein stain and ultrastructure study). Photoexposure granuloma was diagnosed.
Case 2 was a 59-year-old man who had undergone liver tranplantation in 1994. He
was given immunosuppressive and antihypertensive therapy and developed within 4
months a dark rash on the neck opening and nape, sparing photoprotected areas.
Histopathology revealed granuloma annulare. Elastophagocytosis was disclosed by
orcein stain and the ultrastructure study. DISCUSSION: This clinical presentation
of granuloma annulare in two liver transplant recipients is unusual. We discuss
the clinical and histopathological patterns observed in our two cases and the
relationships between granuloma annulare and immunosuppression.
PMID- 11011164
TI - [Microsporum canis mycetoma of the scalp].
AB - BACKGROUND: Mycetoma is a chronic subcutaneous tumefaction with presence of
grains or granules. Etiological agents include bacteria or filamentous fungi.
Mycetoma due to dermatophytes is uncommon, mainly occurring in Africa. To our
knowledge, no case has been reported in the West Indies. Only two observations of
Micosporum canis mycetoma in humans have been reported in the literature. We
report a third case of mycetoma of the scalp caused by this fungus. CASE REPORT:
A 22-year-old woman from Martinique, French West Indies, presented with an
indolent tumefaction of the scalp evolving over five years. She had mental
retardation due to congenital adrenal hyperplasia with 21-hydroxylase deficiency.
The lesion was extracted surgically. Pathology and mycology examinations showed
features of Microsporum canis mycetoma. Two months later, the scalp lesion
recurred and the patient was treated with griseofulvin after surgical extraction.
DISCUSSION: Mycetoma due to dermatophytes is very uncommon, mainly observed on
the scalp and nape of the neck. A history of a skin lesion is frequent, leading
to transcutaneous penetration of the fungus and mycetoma formation. Several
dermatophyte species have been identified as causal agents (Microsporum
ferrugineum, Trichophyton rubrum, Trichophyton verrucosum, Trichophyton
mentagrophytes, Microsporum audouinii, Microsporum langeronii). Microsporum canis
is rarely demonstrated in humans: two cases in children in Africa and Australia.
Our observation was similar to the two cases in the literature: indolent and
mobile tumefaction of the scalp, in a child or young adult, suggestive of lipoma
or epidermal cyst, with excision leading to diagnosis. Association with tinea
capitis and skin or nail involvement can also be observed.
PMID- 11011165
TI - [Lymphoma presenting as Sister Mary-Joseph's nodule].
AB - BACKGROUND: Cutaneous metastasis of the umbilicus is generally associated with
intra-abdominal adenocarcinoma, rarely with a malignant hemopathy. CASE REPORT:
We report a case of lymphoma presenting as Sister Mary-Joseph's nodule, in a 79
year-old man. Histology evidenced small-cell lymphoma. DISCUSSION: Umbilical
metastasis is uncommon, most of these lesions arising from gastric
adenocarcinoma. Only two cases of lymphoma, associated with an umbilical
metastasis have been reported. This case opens the discussion on the fact that
the umbilicus is generally not a site of metastatic spread of lymphomas.
PMID- 11011166
TI - [Erythema annulare centrifugum and relapsing polychondritis].
AB - BACKGROUND: Relapsing polychondritis is a rare systemic disease. Skin involvement
occurs in 20 to 50 % of cases. Cutaneous signs are most often related to a
leukocytoclastic vasculitis. Association of relapsing polychondritis with
neutrophilic dermatosis have also been reported. We report the first case of an
erythema annulare centrifugum-like dermatosis associated with relapsing
polychondritis, with a two years delay between both conditions. CASE REPORT: A 74
year-old man was seen for papulo-erythematous centrifugal annular lesions that
appeared 18 months earlier in a context of bad general conditions. Biological
tests were normal. Several skin biopsies were performed, showing at the beginning
features of drug reaction and then of lupus-lichen. Treatment with
hydroxychloroquine, topical corticosteroids, dapsone and thalidomide were
unsuccessful. In the following months, the patient developed fever and relapsing
bronchitis. Suddenly, a chondritis of the ears appeared, leading to the diagnosis
of relapsing polychondritis. All the cutaneous, chondritic and respiratory signs
disappeared with oral steroid therapy. Two years after the diagnosis of relapsing
polychondritis the patient developed refractory anemia. DISCUSSION: Cutaneous
signs of relapsing polychondritis are frequent and may occur several months or
years before the chondritis. They are polymorphous, but to the best of our
knowledge, a clinical aspect of erythema annulare centrifugum has never been
described. Our observation recalls the sometimes long delay between the cutaneous
and the chondritic signs of relapsing polychondritis and the high frequency of
dysmyelopoiesis in relapsing polychondritis with cutaneous involvement.
PMID- 11011167
TI - [Cutaneous manifestations of Yersinia enterocolitica infection].
AB - BACKGROUND: Cutaneous manifestations occurring in infections due to Yersinia
enterocolitica are usually erythema nodosum, erythema multiforme or cutaneous
vasculitis. The association between Yersinia infection and Sweet's syndrome is
rare. We describe such a case contributing to the discussion on this association.
CASE-REPORT: A 29-year-old woman had a papulo-pustular eruption with fever
associated with arthralgia. The results of the infectious laboratory
investigations were negative but Yersinia enterocolitica type 0.9 was isolated
from a stool culture. The serologic diagnosis of Yersinia enterocolitica using
serum agglutinins was negative. The diagnosis of Sweet's syndrome was made on a
skin biopsy specimen. Search for hematology disease or underlying neoplasia was
negative. The clinical course was rapidly favorable with antibiotic treatment
(ciprofloxacin). DISCUSSION: The diagnosis of Yersinia enterocolitica infection
is difficult. Microbiologic diagnosis of Yersinia infection is best achieved by
isolation of the bacterium from a clinical specimen of involved tissue. The
agglutination test is not highly specific or sensitive. Immunoblotting appears to
be more sensitive.
PMID- 11011168
TI - [Comments on the 'Case for diagnosis' reported by Vieira-mota et al].
PMID- 11011170
TI - [Wasp stings with localized eruption].
PMID- 11011172
TI - [Hypocromatic spots on pigmented skin].
PMID- 11011171
TI - [Familial disseminated amylosis with cutaneous and cardiac predominance by
apolipoprotein A1 mutation].
PMID- 11011173
TI - [Ecchymotic aeras to biopsy].
PMID- 11011174
TI - [Recommendations of the French Society of Photodermatology for systemic PUVA
therapy in psoriasis vulgaris. French Society of Photodermatology].
PMID- 11011176
TI - [Cell therapy: perspectives for curing skin wounds?].
PMID- 11011175
TI - [Management of pain].
PMID- 11011178
TI - [New nail and hair side-effects of cyclosporin].
PMID- 11011177
TI - [Erythematous pemphigus (seborrheic pemphigus)].
PMID- 11011179
TI - [Challenge test for toxic skin reactions to drugs].
PMID- 11011180
TI - [DermIS, University of Erlangen at Nuremberg].
PMID- 11011182
TI - [Guichard Joseph Duverney (1648-1730), first French otologist in the 17th
century].
AB - PURPOSE OF STUDY: Study and understand the role of Guichard Joseph Duverney in
the history of French otology. METHOD: Study of the different works and articles
published about him, linked with reading his principal writings. RESULTS:
Duverney published one of the first complete works on otology titled Traite de
l'organe de l'ouie (Treatise of the organ of hearing) in 1683. Following a first
part containing numerous new notions of anatomy, Duverney developed in the second
part a theory of hearing very similar to that of von Helmholtz. In the third
part, he finally cover several pathologies of the ear without great innovation.
Translated into many languages, this book became the book of reference for all
the otologists of the 17th and 18th centuries. CONCLUSION: Duverney is rightly
considered to be the first French otologist of the 17th century and also, as
certainly one of the first European otologists.
PMID- 11011183
TI - [Maurice Sourdille and the operating microscope].
AB - The authorship of the operating microscope appears to be shared by Nylen, who had
the idea of using a microscope for ear surgery and Gullstrand, who invented the
slit-lamp and who was probably the counsellor of Holmgren in his work on
operative field magnification. Holmgren was the first to use an operating
binocular magnifying glass and Sourdille created the first binocular magnifying
glass designed for microsurgery.
PMID- 11011184
TI - [Tympanoplasty and Sourdille].
AB - In his article published earlier in 1929, Maurice Sourdille proposed two
innovations in middle ear surgery: the tympanomeatal flap and surgery of chronic
otitis. Those events were not only the starting point of a new era of modern
tympanoplasty but also led to the way to the development of middle ear
exploration with purposeful resection of the tympanic framework for accessing to
the windows and for sealing a perforated tympanic membrane.
PMID- 11011185
TI - [A century in the history of chronic ear surgery].
AB - Although some advocated surgery of the tympanic membrane and stapes as early as
early as the end of the nineteenth century, it took a long time for widespread
development. Mastoid surgery had just been born and was to be greatly improved
over the next century. Preservation of the tympano-ossicular its later
reconstruction gradually came into use with the creation of the tympanomeatal
flap and the recent development of middle ear surgery, followed by posterior
tympanotomy and myringoplasty, thus allowing closed tympanoplasty. Likewise, the
ventilation tube, forgotten for more than half a century, has found an important
place in the treatment of chronic otitis with a closed ear drum.
PMID- 11011186
TI - [A century of ostospongiose or the "century" of ostospongiosis?].
PMID- 11011187
TI - [A hundred years of vertigo].
PMID- 11011188
TI - [A century of ENT cancerology].
PMID- 11011217
TI - Potential influence of lipids in diabetic nephropathy: insights from experimental
data and clinical studies.
AB - Diabetic nephropathy is associated with an altered lipid profile characterized by
elevated triglyceride rich lipoproteins, present even in the earlier stages of
the renal disease. Although many experimental studies have demonstrated a
significant deleterious role for hyperlipidemia in both the initiation and
progression of renal injury, data remain more conflicting in humans. A few
prospective studies, mostly in type 2 diabetes, have suggested an independent
role for serum cholesterol level in the subsequent development of incipient or
overt diabetic nephropathy. Furthermore, studies have reported in both types of
diabetes an independent deleterious influence of serum total cholesterol on the
decline in renal function and/or progression of albuminuria. However, the
majority of these studies were post hoc analyses of previously controlled
therapeutic trials with several observational studies not confirming these
findings. It remains controversial whether apolipoprotein E gene polymorphism is
an important factor in the development of diabetic nephropathy. Most of the
interventional studies with lipid-lowering therapy in diabetic nephropathy have
used HMG CoA reductase inhibitors and have been inconclusive. This may be due to
a too short follow-up or insufficient number of patients. Further larger
prospective studies are therefore required to better ascertain the role of lipids
in the progression of diabetic nephropathy.
PMID- 11011218
TI - Post-prandial hyperglycemia. post-prandial hyperglycemia and diabetes.
AB - Post-prandial hyperglycemia (PPHG) is an independent risk factor for the
development of macrovascular complications. It is now recognized that normalizing
post-prandial blood glucose is more difficult than normalizing fasting glucose.
Many factors affect the post-prandial blood glucose excursion. The glycemic index
of the meal depends on the nature of the ingested food and starch composition.
Gastric emptying is influenced by various factors including gut hormones such as
GIP and GLP1, which potentiate insulin secretion, especially in its acute first
phase, now referred to as an incretin effect. They also modulate glucagon
secretion. Post-prandial hyperglycemia is limited by uptake of glucose by the
liver and by inhibition of endogenous glucose production in this organ. In
healthy controls, hepatic glucose production is halved after a meal, whereas in
glucose-intolerant individuals and type 2 diabetics this inhibition is impaired
(20-30% versus 50%). The persistence of endogenous glucose production during the
post-prandial phase appears to be the main culprit in the PPHG. This reduced
decrease in endogenous glucose in glucose intolerant and type 2 diabetic patients
depends not only on the first acute phase of insulin secretion, but above all on
the non-suppressed glucagon level during the post-prandial phase. Glucagon levels
fall in healthy control subjects during the post-prandial phase. Although
peripheral glucose uptake by insulin-dependent tissues is altered in type 2
diabetic patients, it does not appear to be the major cause of the PPHG as there
are patients with insulin resistance but without post-prandial hyperglycemia.
PMID- 11011219
TI - Contribution of total and intact proinsulins to hyperinsulinism in subjects with
obesity, impaired glucose tolerance or type 2 diabetes.
AB - The recent development of specific radioimmunoassays of insulin (Ins) and
proinsulin (PI) led some authors to question the classical data on
insulinosecretion in patients with abnormal glucose tolerance. The aim of this
work was to determine the participation of intact proinsulin (iPI) and its split
fragments to total insulinsecretion in obese subjects and in various stages of
glucose intolerance determined by an oral glucose load according to the WHO
recommendations. Five groups were constituted: non obese controls (C), obese
subjects with normal glucose tolerance (O), non obese subjects with impaired
glucose tolerance (I), obese subjects with impaired glucose tolerance (OI) and
diabetic patients (D). The basal level of total Proinsulin (tPI) of D and OI was
significantly higher than that of C, but the tPI/Ins ratio did not differ between
the five groups. After glucose load, this ratio tended to be higher in D, but not
significantly. No statistical difference between groups was observed for the
iPI/Ins ratio. These results indicate that the determination of tPI is at least
as informative or more than that of iPI. Furthermore, the proportionally constant
participation of PI to insulin secretion observed in various stages of glucose
intolerance suggests that the results obtained in the past with non specific
insulin radioimmunoassays remain valid.
PMID- 11011220
TI - The DECODE study. Diabetes epidemiology: collaborative analysis of diagnostic
criteria in Europe.
AB - The current criteria for the diagnosis of diabetes used in France are now based
on those published by the American Diabetes Association in 1997: fasting plasma
glucose >/= 7.0 mmol/l (126 mg/dl) (previously >/= 7.8 mmol/l (140 mg/dl)), 2
hour glucose >/= 11.1 mmol/l (200 mg/dl) following a 75g oral glucose tolerance
test. However, while the American Diabetes Association recommended that the post
charge test not be used, both the World Health Organisation and the French
Language Association for the study of Diabetes and Metabolic diseases (ALFEDIAM)
retained this test. The DECODE (Diabetes Epidemiology: Collaborative analysis of
Diagnostic criteria in Europe) study analysed the effect of these changes on the
prevalence of diabetes, and whether the changes were justified by the mortality
in the various glycaemic groups, using epidemiological data on close to 30,000
subjects from twenty European epidemiological studies. The prevalence of
diabetes, using fasting rather than the 2-hour glucose concentrations (as had
previously been recommended for epidemiological studies) resulted in changes in
the prevalence of diabetes, an increase or a decrease, depending on the
population studied. The fasting criteria tended to diagnose younger and more
obese subjects than the 2-hour criteria. The subjects who would now be diabetic
with the new fasting diagnostic criteria suffered a high mortality, similar to
that of other diabetic subjects, thus the new criteria can be justified. However,
the diabetic subjects who only have a post-charge diabetic hyperglycaemia (>/=
11.1 mmol/l (200 mg/dl)), are now even less likely to be screened as diabetic,
despite the fact that they have a risk of premature death of the same order as
other diabetic subjects.
PMID- 11011221
TI - What do the needles, syringes, lancets and reagent strips of diabetic patients
become in the absence of a common attitude? About 1070 questionnaires in
diabetic clinics.
AB - The aim was to investigate the fate of injection and monitoring material after
its use by diabetic patients in different countries (France, Belgium, Luxemburg,
Switzeland and Tunisia). Some suitable containers are available for disposal but
little is known about the attitudes of patients and physicians to them. 1 070
questionnaires were completed by patients (age: 50 +/- 18 years; diabetes
duration: 15 +/- 11 years; 2.8 +/- 1.1 injections per day) visiting 109 doctors.
Injections were done at home (72.6%), or both at home and at work (26.6%). At
home: needles, syringes, lancets and reagent strips were thrown directly into the
bin in 46.9%, 49.9%, 52.2% and 67.6% of cases, respectively; and in a closed
plastic bottle in 29. 6%, 28.5%, 28.9% and 19.9% of cases, respectively. Specific
containers were used in 8.6% and 6.3% of cases for needles and syringes,
respectively. 62% of the bottles and containers were thrown directly into the
bin, whereas 15.5% were returned to a pharmacy (4.5% taken to hospitals, 2.9%
were burned). At work: 63% of the patients brought their needles and syringes
home for disposal, 6.9% kept suitable containers at work and 30% threw their
materials directly into local bins. We conclude that awareness should be
increased and the organization of the collection of used material improved.
PMID- 11011222
TI - Case complexity and clinical outcome in diabetes mellitus. A prospective study
using the INTERMED.
AB - The aim of this study was to assess a population of patients with diabetes
mellitus by means of the INTERMED, a classification system for case complexity
integrating biological, psychosocial and health care related aspects of disease.
The main hypothesis was that the INTERMED would identify distinct clusters of
patients with different degrees of case complexity and different clinical
outcomes. Patients (n=61) referred to a tertiary reference care centre were
evaluated with the INTERMED and followed 9 months for HbA1c values and 6 months
for health care utilisation. Cluster analysis revealed two clusters: cluster 1
(62%) consisting of complex patients with high INTERMED scores and cluster 2
(38%) consisting of less complex patients with lower INTERMED. Cluster 1 patients
showed significantly higher HbA1c values and a tendency for increased health care
utilisation. Total INTERMED scores were significantly related to HbA1c and
explained 21% of its variance. In conclusion, different clusters of patients with
different degrees of case complexity were identified by the INTERMED, allowing
the detection of highly complex patients at risk for poor diabetes control. The
INTERMED therefore provides an objective basis for clinical and scientific
progress in diabetes mellitus. Ongoing intervention studies will have to confirm
these preliminary data and to evaluate if management strategies based on the
INTERMED profiles will improve outcomes.
PMID- 11011224
TI - [Survival analysis of diabetic patients on dialysis in Guadeloupe].
AB - BACKGROUND: Both diabetes and hypertension, two conditions that can lead to renal
failure, have a high prevalence in Guadeloupe. OBJECTIVE: To determine the
clinical and epidemiological features of diabetic patients on end stage renal
failure and to evaluate their survival. PATIENTS AND METHOD: Data of the
Guadeloupe Kidney registry were analysed for patients who began chronic dialysis
during 1978-1997. Follow up information on survival status was obtained up to
January 26(th) 1999. Cox proportional hazard analysis was used to determine the
relative risk (RR) of death between levels of independant variables. RESULTS:
There were 784 dialysis patients of whom 174 (22%) were diabetics. Among the
latter, there were 97 women (55,7%), mean age at the start of dialysis was 60.6
years (range 26-83) and arterial hypertension was present before the start of
dialysis in 67% of them. Median survival MS (95%CI) was significantly lower in
diabetics 42 months (31-52) than in non diabetics 83 months (70-96), p<10(-4). In
diabetics, the cumulative probability of survival was 83% (1 year) and 39% (5
years) and the RR of death (95% CI) were 1.90 (1.10-3.22) and 3.43 (2.00-5.87)
for diabetics admitted in dialysis in age-class 55-64 years and 65-83 years,
respectively, when that for age-class 54 years was set at 1. 00. The RR for
diabetics was 1.67 (1.33-2.10) relative to non diabetics. CONCLUSION: Prospective
studies are warranted to describe the role of comorbid conditions in diabetic
patients survival. Prevention of degenerative complications should be a priority
in this population.
PMID- 11011223
TI - Possible activation of auto-immune thyroiditis from continuous subcutaneous
infusion of genapol-containing insulin.
AB - A case of a type 1 diabetic woman with auto-immune thyroiditis is reported, in
whom repeated exposure to insulin containing Genapol(R) (polyethylen
polypropylenglycol) over 3 years reproducibly parallels with an increase of serum
TSH (thyroid-stimulating hormone) above the normal limit. Previously, adverse
effects of Genapol(R) insulin have been related to its intraperitoneal
application, and thought to be restricted to anti-insulin-immunity; activating
effects on thyroid auto-immunity have been repeatedly disputed. We suggest that
Genapol(R) insulin should be replaced by other insulin preparations with a better
safety record.
PMID- 11011225
TI - Telling about diabetes canhelp disease acceptance in indulin dependent diabetes.
A clinical experience .
AB - Type 1 diabetes (IDDM) is an original, chronical illness which concerns the
physician as well as the patient, who is strongly implicated in the self
management of his treatment. In order to help them to cope with their illness, 31
IDDM patients patients usually attending our diabetology unit were submitted to
an open questionaire. We considered that IDDM may be a psycho-somatic disease,
and that psychological factors may interfere with glycemic balance. The purpose
was 1) to explore the patient's relationship to himself as a diabetic subject,
while listening to his "story"; 2) if telling his story is able to reduce his
burden or if there is a risk of setting down a psychic level. In fact, it allowed
a better self-knowing and understanding, so that the patient could get back some
power against illness; it appears a useful tool for a better dialog between the
physician and the patient.
PMID- 11011226
TI - [Is diabetes mellitus a sufficient condition to suspect hemochromatosis?].
AB - Genetic Hemochromatosis (GH) is a highly prevalent autosomal recessive disorder,
which outcome has been dramatically improved by early phlebotomy. Attempts to
screen for the disease, using biological and genetic approaches, are currently
under evaluation. Diabetes mellitus often complicates GH. However, as it occurs
late in the course of the disease, in most cases when cirrhosis is already
present, its usefulness for the screening of GH seems reduced. Diabetes mellitus,
when isolated, appears also as a poor predictor of hemochromatosis. Indeed, the
risk of being carrier of the disease is not increased in diabetic patients
compared with non diabetic sujects. This risk is however highly enhanced by the
co-existence of cirrhosis. Thus, in the face of a newly diagnosed diabetes
mellitus, the search for hemochromatosis must be performed only when it
associates with cirrhosis or with other evocative clinical conditions.
PMID- 11011228
TI - [Treatment of type 2 diabetes].
PMID- 11011227
TI - [Diabetic retinopathy in Dakar and review of African literature: epidemiologic
elements].
AB - Literature review shows that in the African Sub-Sahara, prevalence of diabetic
retinopathy is between 15 and 52%, the main age being the fifties (between 45.5
and 53.25 years in our cases); after 5 years of diabetes evolution (8.45 +/- 6.93
years in our cases) men being two to three fold more affected than women; non
insulin dependent diabetes representing 77% and insulin dependent diabetes 23%.
The type of retinopathy is usually mixed, both edematous and ischemic (88% being
non proliferative). Retinopathy concerned mainly non obese, non insulin dependent
diabetics in our cases. Risk factors are poor glycemic control and arterial
hypertension. Diabetes duration was the sole and most evident risk factor.
Diabetes duration was 5.28 +/- 5.28 years when retina was normal and reached 8.58
+/- 5.33 years for Stage II and 12.8 +/- 6.31 years for retinopathy Stage III and
16.75 +/- 7.25 years for retinopathy Stage IV. These factors, delayed diagnosis
and diabetes progression in Africa justify improvement of diabetes care by
multidisciplinary team to prevent blindness.
PMID- 11011229
TI - [Introduction].
PMID- 11011230
TI - [General method].
PMID- 11011231
TI - [Strategy for documentary research].
PMID- 11011232
TI - [Strategies for care of the type 2 diabetic patient excluding care of
complications. Recommendations of ANAES (National Agency for Health Accreditation
and Evaluation March 2000].
PMID- 11011233
TI - [Health care in non-insulin dependent diabetics in lower Normandy].
AB - To contribute to better quality health care for patients with type 2 diabetes
mellitus living in the French Department Basse-Normandie, the Regional Union of
General Practitioners (URML) and the Regional Union of the Nation Health
Insurance (URCAM) studied ambulatory practices in this population in 1999. Eight
hundred diabetics whose health care reimbursements suggested they were not
followed by a specialized center were studied: 400 received a mailed
questionnaire and for the 400 others, another questionnaire was filed out by the
primary care physician. The physicians' responses demonstrated that they do not
feel certain recommended complementary investigations are always necessary for
following diabetic patients (microalbuminuria, glycated hemoglobin, search for
neuropathy, ophthalmology consultation). Interaction with diabetologists,
nutritionists and chiropodists was found to be insufficient. Globally, the
responses of the diabetics was coherent with the physicians' statements,
providing further precision concerning health care delivery and propositions for
improvement. These results can be used to better target education programs for
associations, specialists and general practitioners.
PMID- 11011234
TI - [A public health program for better patient management].
PMID- 11011235
TI - [A public health program for better patient management].
PMID- 11011236
TI - [Epidemiology of diabetes in metropolitan France].
AB - The statistical analysis of French HealthCare's database, containing total
reimbursements to affiliates and a listing of delivered drug prescriptions in the
form of specific drug codes, allowed us to update data on the epidemiology of
diabetes. This study, performed during the first trimester of 1999 on the entire
population of metropolitan France, found an overall prevalence of 2.78 % for
diabetes in all affiliates of the regimen (Regime general) stricto sensu (3.06 %
in the general population), 0.41 % corresponding to diabetic treated exclusively
with insulin (0.44 % in the overall population) and to 0.12 % receiving both
insulin and oral hypoglycemic agents concomitantly (0.13 % in the general
population). The average age of diabetics, irrespective of the treatment they
were receiving, was 63.1 years with a sex ratio M/F of 1.04. These findings
confirm epidemiological forecasts which had predicted a significant increase in
the prevalence of diabetes over the past few years. The study also confirmed data
from the medical literature concerning geographic disparities in the epidemiology
of this disease except for the results obtained in the north of France, a region
generally thought to have a lower prevalence of diabetes, and which was found to
have a prevalence equal to even greater than the national average.
PMID- 11011238
TI - [Modalities of follow-up on non-insulin treated diabetics treated in metropolitan
France in 1998].
AB - The statistical analysis of French HealthCare's database allows a retrospective
evaluation of the overall clinical care given to diabetics in the light of the
guidelines (RBPC) promulgated by the National Agency of Health Accreditation and
Evaluation (ANAES). This database contains no information on the stage of the
disease process, the completeness of the clinical evaluation (neurological or
foot examination) or the results of significant blood tests. We studied the
follow-up care given to diabetics whom we were able to identify by isolating
reimbursements for hypoglycemic agents using their corresponding drug codes.
Considering the time needed for this new drug-coding system to become fully
operational, the results can be extrapolated to the entire population of non
insulin treated diabetics. In 1998, almost all follow-up care was provided by
general practitioners since only 5.5 % of the patients consulted an
endocrinologist during the year studied. Blood sugar was generally monitored with
fasting blood sugars rather than HbA1c which was only prescribed in 41.3 % of the
patients during the final six months of the period under consideration. Screening
and follow-up for degenerative complications were insufficient. Fewer than 40 %
of the patients had received reimbursement for an ophtalmological consultation
during the preceeding year and fewer than 30 % had an ambulatory resting EKG over
the same time period. A certain number of factors were studied in order to
determine if they were correlated to better clinical follow-up. The best follow
up was encountered in patients who had a consultation with an endocrinologist at
least once during the year, those who were exonerated from co-payments (ALD 30)
and finally, those aged between 40 and 59 years (at least with respect to
appropriate laboratory tests).
PMID- 11011237
TI - [The cost of diabetes in metropolitan France].
AB - The statistical analysis of French HealthCare's database, containing total
reimbursements to affiliates and a listing of delivered drug prescriptions in the
form of specific drug codes, allowed us to update data of the cost of diabetes.
This study, realized during the first trimester of 1999, used the combined
databases of 110 local healthcare offices (CPAM) among the 128 existing in
metropolitan France. French Social Security spent a total of 31.9 billion francs
(4.9 billion euros) in care given to diabetics (or 24,137 francs per patient)
comprised by 14.2 francs (2.2 billion euros) for in-hospital care and 17.7
billion francs (2.7 billion euros) for outpatient services. The total expenses
for diabetic patients represented 4.7% of French Social Security's overall
expenses for all its affiliates. The differential cost of diabetes (the
difference, at equivalent ages, between cost generated by diabetic patients and
those attributable to the remainder of the affiliated population) was estimated,
for the generalized health-care regimen (regime general) in 1998, to be 13.3
billion francs (2.0 billion euros). These figures underscore the need to
reinforce prevention and screening for end-organ complications since it is
generally admitted that the disease's high cost is essentially related to its
complications.
PMID- 11011240
TI - [Totally reimbursed care for type 2 diabetes in 1994: characteristics and follow
up].
AB - Non-insulin-dependent diabetes mellitus (NIDDM) is an important health issue in
France. According to projections from current data, the problem should increase
over the upcoming years. The aim of this study was to determine the
characteristics of patients with NIDDM who are enrolled on the list of 30 long
term diseases (ALD30) and examine their follow-up and disease-related
complications. This study was performed with the data base established by the
French National Health Insurance for Salaried Workers (CMANTS) in 1994. Diagnosis
and medical information were coded by official physicians, who either examined
the patients or consulted their primary care physician (69% of the cases), or
relied on available medical records. Eight thousand two hundred forty-seven
patients (sex ration=0.95) with NIDDM enrolled on the long term disease list were
included. Mean age was 65.1+/- 0.13 years (m+/- SEM). More than one blood glucose
level per year was available for 89% of the patients and an HA1c assay in only
34%. In addition, for patient follow-up at least once a year, 80%, 47%, and 42%
of the patients had a serum creatinine assay, a funus examination, or an
electorcariogram respectively. Irrespective of the criteria retained (fasting
glucose=1.26 g/l; fasting glucose=1.40 g/l) there was a high percentage of
patients whose level was well above the limit (75% and 63% respectively). For
HbA1c, only a quarter of the patients had values lower than the limits defined by
the ANAES and AFFSAPS guidelines. The percentage of diabetic patients without
complications was 41% (hypertension excluded). The most frequently observed
complications isolated peripheral vascular conditions (31%). These results were
obtained from a database created in 1994, before guidelines on type 2 diabetes
were officially published. They can serve as a reference to follow medical
practices.
PMID- 11011239
TI - [Analysis of health insurance benefits: material and methods].
AB - The statistical analysis of national health insurance's database, containing a
record of the care reimbursed to affiliated members and delivered drugs in the
form of special pharmacy codes, enable us to evaluate the follow-up care given to
diabetics, to update epidemiological information and to determine the actual cost
of diabetes. The method used consisted in the identification of diabetics by
isolating patients who received hypoglycemic agents during the 3-month inclusion
period followed by a retrospective determination of total reimbursements made
through the 128 local health offices (CPAM) located in metropolitan France in
order to study the reimbursed care (medical consultations, procedures and drug
prescriptions) given to diabetics over the preceding 12 month period. Considering
that the pharmacy coding system was still incomplete at the time the study was
undertaken, we had to verify that the population selected by the coding system
was only partially operational, requiring a calculation involving weighted
coefficients. Finally, we needed to take into account the fact that the resulting
data contained virtually no information on facilities receiving a once a year
total budget allocation (all public hospital).
PMID- 11011241
TI - [Pharmacoepidemiology of diabetes: assessment of good use of oral antidiabetic
drugs].
AB - Diabetes' treatment is specific; therefore diabetic patients can be identified by
the prescription of antidiabetic drugs. This pathology is characterized by
chronicity and occurrence of complications which need additional medications. All
the drugs have official use guidelines due to drug interactions and/or
physiological status of the patients. To evaluate how these guidelines are
followed in general practice, we used a data base from the French Health care
System. Two thousand eight hundred and ninety eight (2 898) prescriptions on
which, at least, one oral antidiabetic drug was noticed, were analysed. The
number of drugs on each prescription was between 1 and 18 (mean (5,6 +/- 2,9)).
Considering the drugs which need precautions of use in association with
sulfonylureas, coprescription occurred with B-bloquants and non steroid anti
inflammatory drugs in 18 and 17 % of the cases respectively. The drugs which need
precautions of use in association with biguanides were diuretics, oestrogens
and/or progestatives and steroids, coprescribed in 28, 1, 1 % of the cases
respectively. Percentages of coprescriptions which need precautions of use were
quite high. The relevance of detected coprescriptions. and the compatibility
between recommendations for "good prescription" and "real prescription practice"
should be taken into account considering diabetic patients' characteristics.
PMID- 11011242
TI - [Description of type 2 diabetes mellitus in residents of Ile-de-France aged at
most 70 years].
AB - Our study of patients with type 2 diabetes mellitus residing in the Paris area
(Ile-de-France) aged 70 years or younger included 1 591 patients examined by
national health insurance expert physicians who also filled out a self
administrated questionnaire. Their primary care physicians also answered a
questionnaire (79% participation, indicating their personal implication). We
found that diabetes was most often discovered during regular check-ups. Single
drug regimens were the most widely used. Sulfamides were prescribed for 77% of
the patients. Among the 912 patients who were overweight (BMI > 28 Kg/m2), 34.3%
were taking sulfamides alone despite the fact that metformin is recommended as
the first intention drug for these patients. Blood pressure control was not
satisfactory in 30% of the patients who were treated or not for high blood
pressure. This proportion rose to about 50% among treated patients alone. The
patients appeared to be knowledgeable about the risk of complications,
particularly ocular complications. They were aware of a certain number of
messages but the results would suggest difficulty in application.
PMID- 11011243
TI - [Identification of factors hindering better management of patients with type 2
diabetes].
AB - The aim of this study was to help improving management of patients with type 2
diabetes by evaluating their knowledge of the disease and its treatment and by
identifying factors which might influence management. A questionnaire was sent to
diabetic patients taking oral antidiabetic drugs affiliated to one of the three
main national health insurance schemes in the French Departments Seine-Maritime
and Eure. Four hundred responses were analyzed. Patient knowledge of diabetes and
its complications, follow-up, surveillance and dietary control were rather poor.
Use of a personal diary (used by 24%) was associated with better knowledge of the
disease and better participation in follow-up and treatment. Actions aimed at
better education of diabetic patients promoting use of a personal diary would be
helpful to improve disease management, necessary to reduce the risk of
complications.
PMID- 11011244
TI - [Malignant duodenal stenoses: can endoscopic or radiological insertion of metal
stent replace surgical derivation?].
PMID- 11011245
TI - [Iron deficiency in patients over 60 years. Descriptive study in the consultant
population of health screening centers].
AB - AIM: The aim of the study was to evaluate the frequency of iron deficiency with
serum ferritin in elderly population, and to appreciate the opportunity of early
screening according to digestive diseases. SUBJECTS AND METHODS: Data were
collected from 3524 men and 3120 women aged 60 to 75 years during a health
screening examination. Evaluation of diagnosis and treatment were obtained
through questionnaire completed by treating physician. RESULTS: The frequency of
hypoferritinemia was about 2.3% in our population (hypoferritinemia was defined
by serum ferritin<20 microg/L or between 20-40 microg/L if C reactive protein was
> 12 mg/L). Anemia was found in 3.3% of patients. Logistic regression model
adjusting for multiple variables was used to examine factors associated with
hypoferritinemia. The probability was greater among non-anemic patients with
chronic digestive bleeding (odds-ratio: 2.3), or with positive occult blood
testing (odds-ratio: 2.3). Information about the medical follow-up was obtained
in 81% of patients with hypoferritinemia. A digestive exploration was made in 38
cases. Digestive disease was found among 24.3% patients with hypoferritinemia,
and three colorectal cancers were observed. CONCLUSION: The screening of
hypoferritinemia in elderly population examined in health screening centres could
not be recommended as its frequency was low in this population, despite a strong
correlation between hypoferritinemia and digestive diseases.
PMID- 11011246
TI - [Palliative endoscopic treatment of malignant duodenal stenosis by metal
prosthesis].
AB - PURPOSE: To evaluate the efficacy of through-the-scope metal stents for
palliation of malignant duodenal stenosis. MATERIAL AND METHODS: Fourty two
patients with malignant primary or secondary duodenal stenoses who were treated
with a through-the-scope metal stent were analysed. When obstructive jaundice
occurred either before, during, or after the initial episode of gastrointestinal
luminal obstruction, a biliary stent was inserted. RESULTS: Duodenal metal stents
were deployed in 40 patients. Endoprosthesis insertion led to restoration of oral
intake in 39 patients. The procedure was not associated with morbidity or
mortality. During a mean follow-up of 9.7 weeks, adequate oral intake was
maintained in 38/39 cases. Tumour in-growth led to stent occlusion in 4 cases and
re-cannulation was obtained by placement of another stent within the original
stent. Obstructive jaundice occurred during the course of the illness in 32
patients and was successfully treated with a biliary metal stent in all cases.
CONCLUSIONS: Endoscopically placed metal stents offer an effective, well
tolerated alternative to surgical palliation in case of incurable malignant
obstruction to gastric outflow.
PMID- 11011249
TI - [Pre-test].
PMID- 11011247
TI - [Peroxisome proliferator-activated receptor (PPAR) gamma: a new target for the
treatment of inflammatory bowel disease].
AB - The peroxisome proliferator-activated receptor (PPAR) gamma is highly expressed
in the colon mucosa. In vitro, it regulates inflammation. AIM: To evaluate the
anti-inflammatory functions of PPARgamma agonist during a trinitrobenzene
sulfonic acid (TNBS)-induced colitis in mice. METHODS: Colitis was induced in
Balb/c mice after intra-rectal administration of TNBS. The intensity of
inflammation was assessed 2 and 5 days after colitis induction by macroscopic and
histologic scores and by the quantification of colon myeloperoxidase (MPO), IL-1B
and TNFalpha mRNA concentrations. The therapeutic role of PPARgamma agonist given
by oral gavage was assessed in preventive and treatment modes. RESULTS: TNBS
induced severe macroscopic and histologic lesions, with high mucosal MPO, IL-1B
and TNFalpha mRNA concentrations. PPARgamma agonist given preventively or in
treatment mode allowed a significant decrease of macroscopic and histologic
scores through a normalization of MPO, IL-1B and TNFalpha mRNA concentrations.
CONCLUSION: PPARgamma agonist decreases the intensity of TNBS induced colitis
through normalization of IL-1B and TNFalpha expression. PPARgamma agonists may be
proposed as new therapeutic agents in inflammatory bowel diseases.
PMID- 11011248
TI - [Natural history of chronic alcoholic pancreatitis].
PMID- 11011250
TI - [Angina-like chest pain: physiopathology, diagnostic measure and treatment].
PMID- 11011251
TI - [Chest pain from hypertrophic esophageal muscles].
PMID- 11011253
TI - [Answers to the pre-test].
PMID- 11011252
TI - [Interview: questions to Pr Jean-Paul Galmiche].
PMID- 11011254
TI - [Biliary prosthesis and malignant obstruction of extraheptic bile ducts].
PMID- 11011255
TI - [Pegylated interferon: new progress in treatment for chronic hepatitis C].
PMID- 11011256
TI - [Malignant obstructive jaundice: the role of percutaneous metallic stents].
AB - OBJECTIVES: Efficiency evaluation of percutaneous metallic stents in palliative
treatment of malignant biliary obstruction. METHODS: One hundred sixteen
percutaneous metallic stents were implanted in 80 patients with malignant biliary
obstruction. Thirty-five patients had hilar obstruction, 32 patients obstruction
of the common bile duct and 12 patients obstruction of a bilioenteric
anastomosis. RESULTS: Adequate biliary drainage was achieved in 79 patients.
Early complications occurred in 23.75% of patients; 12.5% of patients died within
30 days. The procedure-related mortality rate was 5%; 18.75% of patients showed
recurrent jaundice after an average of 175 days. CONCLUSION: Percutaneous
metallic stents are an efficient means of treating malignant biliary strictures,
particularly of upper biliary obstructions. However, this treatment has risks and
limits that require careful patient recruitment.
PMID- 11011257
TI - [Evaluation of nursing care during treatment of viral hepatitis C by interferon].
AB - OBJECTIVE: Interferon alpha treatment requires parenteral administration and some
patients receive injections from nurses. The aim of this study was to evaluate
the role of nursing care during ambulatory treatment of hepatitis C by interferon
alpha. METHODS: A questionnaire was sent by mail to all nurses who practice
ambulatory care in the Val de Marne region (n =545). RESULTS: One hundred
fourteen questionnaires were returned (return rate: 20%). Among these nurses,
only 42 (37%) were caring for at least 1 patient for the treatment of hepatitis C
by interferon. In the 16 months before the survey, these 42 nurses had cared for
135 patients. The nurses cared for the patients throughout the entire treatment
in 81% and only to teach them in 19% of cases. The time spent for each injection
was 12 min 48 sec, 2 min 42 sec for the injection itself, 3 min 54 sec to answer
to patient's questions, 3 min 30 sec for psychological support, and 2 min 48 sec
for unspecific time. In relation to hepatitis C and interferon treatment, 74% and
64% of the nurses felt that patients asked questions they did not ask their
physician. Seventy seven of the nurses felt they were did not have enough
training to answer the questions. Psychological support for the patient was noted
as important or very important by 38 % of nurses. CONCLUSIONS: The role of nurses
during interferon treatment is not limited to injecting the drug. Advice and
psychological support takes up most of the time spent with patients. Specific
training and better collaboration with the physician who prescribes the treatment
are needed.
PMID- 11011258
TI - [Living donor in liver transplantation. Present and future alternatives].
PMID- 11011259
TI - [Yellow nail syndrome associated with intestinal lymphangiectasia].
AB - The yellow nail syndrome, a combination of yellow discoloured nails, lymphedema
and pleural effusions, is a rare clinical condition. We report a case of the
yellow nail syndrome associated with intestinal lymphangiectasia revealed by
chylous ascites and protein-losing gastroenteropathy. This association reported
in only three cases in the literature leads us to discuss the relations between
yellow nail syndrome, primitive intestinal lymphangiectasia and primary lymphatic
disorders.
PMID- 11011260
TI - [Peritonitis with Mycobacterium avium complex in a patient with alcoholic
cirrhosis].
AB - Before highly active antiretroviral therapy were available, disseminated
Mycobacterium avium complex infection was common in adults with HIV. Diagnosis
was often made by blood culture in these immunocompromised patients. Although
Mycobacterium avium complex disease can involve any organ of the body, infection
of serosal surfaces is very rare. Mycobacterium avium complex peritonitis is rare
and usually occurs in immunocompetent patients with chronic ambulatory peritoneal
dialysis. We report a case of Mycobacterium avium complex peritonitis in a
patient with alcoholic cirrhosis with no evidence of HIV infection. Diagnosis was
made by culture of a lymphocytic ascites which showed Mycobacterium avium complex
at 4 weeks. Interestingly, blood and hepatic cultures remained negative. At three
months, marked improvement occurred with antimycobacterial treatment, so that
orthotopic liver transplantation could be performed.
PMID- 11011261
TI - [Primary T-cell lymphoma of the common bile duct].
AB - Involvement of the gastrointestinal tract is frequently reported among the
extranodal sites of non-Hodgkin's lymphoma, but primary lymphoma of the common
bile duct is extremely rare. We report the case of a 29-year-old man who
presented with obstructive jaundice, leading to the diagnosis of high-grade
primary non Hodgkin's T-cell lymphoma, originating from the extrahepatic biliary
tract, and confirmed by endosonography and magnetic resonance cholangiography.
This patient was treated by sequential chemotherapy without resection and
remained in complete remission after one year.
PMID- 11011262
TI - [Bronchiolitis obliterans with organized pneumonia and hemorrhagic rectocolitis].
PMID- 11011263
TI - [Gastric heterotopia in the rectum: a new case].
PMID- 11011264
TI - [Delayed urticaria with oxaliplatin].
PMID- 11011265
TI - [Lymphocytic colitis due to Modopar].
PMID- 11011266
TI - [Interferon and cryoglobulinemia: how to inject without precipitation].
PMID- 11011267
TI - [Digestive endoscopy aanesthesia: data from the SFAR].
PMID- 11011268
TI - [Reply from Remy Dumas to Andre Lienhart].
PMID- 11011269
TI - [Office-based colonoscopy with possible sedation as requested performed by the
endoscopist: a method also possible in France].
PMID- 11011270
TI - [Reply from Remy Dumas to Bernard Maroy and Philippe Moullot].
PMID- 11011271
TI - [Reply from Denis Grasset, Christian Seigneuric and Jean-Jacques Morfoisse to
Bernard Maroy and Philippe Moullot].
PMID- 11011272
TI - [Prevention of hemolytic disease of the fetus and the newborn: it is necessary to
act].
PMID- 11011273
TI - Echographic signs of trisomy 21 in the second trimester of pregnancy: actual
value after analysis of the literature.
AB - OBJECTIVE: To evaluate the interest and to compare the major echographic signs of
Down syndrome in the second trimester of pregnancy. METHODS: A bibliographic
research has been performed for most of the echographic signs known and studied
until now. For each study and in average for each sign, we have computed its
sensitivity, its specificity, its positive and negative predictive values using
the results of the different authors. Then, we have compared the benefits/risk
ratio for each of these signs: the number of Down syndrome cases detected versus
healthy fetus lost due to amniocentesis complications. RESULTS: The different
signs can be ranked according to their benefits/risk ratio from top to bottom as
follows: nuchal skinfold thickness, wide space between first and second toe,
pyelectasis, large iliac angle, short humerus, short femur, hypoplasia of the
middle phalanx of the fifth digit. CONCLUSION: These results suggest that second
trimester echographic signs of Down syndrome must be evaluated as a function of
the Down syndrome risk in the population under study. The presence of these signs
does not always justify an amniocentesis; it should lead to a re-evaluation of
the individual risk of a Down syndrome (a chart is given to guide this re
evaluation).
PMID- 11011275
TI - [Repetition of corticoid treatment for fetal lung maturation: clinical and
experimental scientific data].
AB - Before 34 weeks, one course of antenatal corticosteroids significantly decreases
neonatal mortality and morbidity. Courses are repeated every week, because of
their alleged loss of efficiency after 7 days, although the relative benefits and
risks of repeated courses are poorly known. Data from the literature suggest that
improvement in lung function after repeated courses depends on the reduction of
the treatment/birth interval and not on the rise in the cumulative dose. These
benefits must be balanced against the risk of decreased birth weight induced by
repeated courses. Because of their effect on fetal growth, weekly courses of
corticosteroids should no longer be given systematically. In clinical practice,
pregnancies at high risk of preterm delivery must be reassessed every week before
prescribing a new course. Both better understanding of treatment duration of
corticosteroids and randomized controlled trials comparing one and multiple
courses are needed to improve antenatal management of neonatal respiratory stress
syndrome.
PMID- 11011274
TI - [Parkinson's disease and pregnancy: case report and literature review].
AB - Parkinson's disease begins before the age of 40 in only 5% of patients. We report
a case of pregnancy in a 35-year old woman with Parkinson's disease. The patient
was treated by levodopa associated with benzerazid. No effect was observed on the
pregnancy and the fetus. Only the symptoms were moderately worsened. A literature
review is performed.
PMID- 11011276
TI - [Infraclinical breast lesions: apropos of a retrospective study of 261 cases].
AB - OBJECTIVE: To determinate the rate of malignant lesions discovered after surgery
for nonpalpable breast lesions diagnosed by radiology. TOOLS AND METHODS: We
performed a retrospective study of 261 patients who underwent surgery for
nonpalpable breast lesions at the Saint-Etienne University Hospital between 1991
and 1998. We included women who did not have any palpable breast lesion. We
excluded bilateral lesions and nonpalpable lesions associated with a palpable
lesion in the same breast. We grouped outcome by alarming signs, those of
complementary exams such as mammography, ultrasound, fine-needle aspiration
biopsy and setreotaxis core needle breast biopsy in their sensitivity,
specificity and predictive values, and classed results by pathology and type of
surgery performed. All nonpalpable lesions were localized by stereotaxis
maneuvers. RESULTS: In our series, 61.7% of the patients were seen for individual
detection, 3% had participated in mass screening programs and 35.3% were referred
for suspected conditions. The predictive value of malignant lesions on
mammography, analyzed in all cases and interpreted in 275, was 42.2%. The
sensitivity and specificity of ultrasound exams performed in 50.2% of the cases
were 85% and 91% respectively. Fine-needle aspiration biopsy and core needle
biopsy were performed in 45 (18%) and 23 (9%) cases respectively. Twelve patients
underwent total mastectomy with axillary dissections, 58 had tumorectomy with
axillary dissections, and 191 had simple tumorectomy. Benign lesions were found
in 128 (49.1%) cases, atypical hyperplasia in 10.7%, carcinoma in situ in 57
(cases 21.8%). The rate of malignant lesions was 38.6%. I was 50.9% when
borderline lesions (atypical hyperplasia and in situ lobular carcinoma) were
included. CONCLUSION: In our series, 38.6% of all nonpalpable operated breast
lesions were cancers. Ultrasound, fine-needle aspiration and needle core biopsy
showed high sensitivity and specificity allowing good biopsy outcome.
PMID- 11011277
TI - [Complications of vaginal hysterectomy on non-prolapsed uterus].
AB - OBJECTIVE: To assess our rate of complications after vaginal hysterectomy and
those described in the literature, particularly in high risk groups such as
obese, nulliparous women with previous abdomino-pelvic surgery or after GnRH
administration. METHOD: We retrospectively looked for complications in 490
patients who underwent vagina l hysterectomy between 1990 and 1998: infections,
hemorrhage, intraoperative complications, thrombophlebitis or pulmonary embolism,
postoperative complications up to one month. The chi-squared test, t test for
equality of means and Fisher's exact test were used for statistical analysis.
RESULTS: The complication rate observed in our series (20.7%) was similar to
those reported in the literature. We found no difference in the obese group
(n=109) the nulliparous women (n=34), after GnRH administration (n=24) or i women
with previous abdomino-pelvic surgery (n=128). Heavy bleeding was not increased
by morcellation. CONCLUSION: Vaginal hysterectomy is easy and safe. The vaginal
route is the best way for obese subjects and can be carried out in most cases,
especially in nulliparous women or after GnRH analogs, even when morcellation is
necessary, without increasing morbidity.
PMID- 11011278
TI - [Regret after tubal sterilization].
AB - OBJECTIVE: To examine thoroughly the profile and motivations of a group of women
who regretted sterilization so much that they were prepared to undergo reversal
microsurgery or in vitro fertilization treatment. MATERIAL: and methods. The
study followed one hundred women from their first consultation for a period of 3
years in order to analyze the outcome of their initial decision. RESULTS:
Analysis of the circumstances at the time of the sterilization indicate 3 main
factors which later caused the women to regret the decision Three years after the
initial consultation, 69% of the patients have withdrawn from further
investigation and /or treatment for different reasons analyzed in this study. 17
of the patients have undergone reversal microsurgery and 14 have attempted one or
more in vitro fertilization treatments. Of these 31 patients, 12 (38.7%) have
given birth to at least one child. CONCLUSION: These results sufficiently prove
that tubal sterilization is worthy of consideration as much by the patient as by
the physician as a method of irreversible contraception despite the developments
in tubal microsurgery or in medically assisted procreation.
PMID- 11011279
TI - [Prenatal screening for trisomy 21 with maternal serum markers: information for
decision-making in pregnant women].
AB - INTRODUCTION: French health professionals are now required to provide relevant
information on the test screening for Down syndrome and its possible implications
when making the test available to pregnant women. A questionnaire was designed to
assess prescription modalities, explanation of results, opinion on the
information received when test was offered and test results were given, and
likely decision after screening. RESULTS: The response rate was 39% (1473
questionnaires analyzed). In 90.5% of the answers, women declared that an
interview had preceded test prescription. 61.2% of women were satisfied with both
the clarity and quantity of explanations provided and 57.6% considered that the
information had helped them decide to undergo or refuse screening. 54.1% were
satisfied with the explanations of test results. Amniocentesis was proposed to
125 women, 79.2% of which decided to undergo the procedure. Their opinion
concerning explanations of test results was similar to that of women who refused
amniocentesis or had not yet made up their minds. CONCLUSION: Such results
demonstrate the necessity to improve and adapt the information delivered by
health professionals, keeping in mind that in this type of situation, decision
making requires the rapid integration of complex information.
PMID- 11011280
TI - [Maternal mortality in the maternity ward of Befelatanana. University Hospital of
Antananarivo].
AB - OBJECTIVE: A retrospective study was conducted to assess mortality rates at the
Befelatanana Women's Hospital from January 1st 1988 through December 31st 1997,
define trends, study causes and identify problems encountered during treatment
and those related to the referral system, in order to improve prevention and
patient management MATERIAL: and method. Birth and death registries, operation
reports and patient charts were analyzed. All maternal deaths wether of direct or
indirect obstetrical origin were considered. RESULTS: There were 997 cases of
maternal death among 91, 032 births, i.e. 1.09% or 1,245 maternal deaths per
100,000 live births. Among direct obstetrical causes of death (93%), 65.8%
involved infectious complications and 22.9% renal and vascular
complications.Other causes were anesthesia accidents and thrombolic events. Among
the direct obstetrical causes, complicated delivery was responsible for 57.4% of
the deaths and 42.6% of the abortions. Indirect obstetrical causes were due to
malaria (68.6%), heart disease (21.4%) and asthma (10%). DISCUSSION: This high
rate of maternal death illustrates the serious situation of obstetrics in our
region. Our aim is to reduce this rate by promoting the Birth Place Without Risk
program and improving management conditions. Implementation of this ambitious
program requires implication of political decisions makers convinced of the
importance of improving women's conditions and the health care system in
Madagascar.
PMID- 11011282
TI - [Waldmann disease and pregnancy].
AB - Waldman disease, also called intestinal lymphangiectasis, is a protein-loosing
enteropathy caused by anomalous intestinal lymphatic canals. The condition is
transmitted by autosomal dominant inheritance. Diet therapy including medium
chain triglycerides improves the disease course. The condition occurs in early
childhood. We report a case observed in a pregnant woman with intestinal
lymphangiectasis. She delivered a full-term infant and experienced no major
complications.
PMID- 11011281
TI - [Determination of acceptability of 2 cutaneous estradiol gels, in a dose of 1.5
mg daily].
AB - OBJECTIVE: The aim was to compare acceptability of a percutaneous 0. 1% estradiol
gel (Gel A, Estreva(R) Gel, Laboratoire Theramex, Monaco) to that of an 0.06%
estradiol gel (Gel B, Oestrodose(R), Laboratoires Besins-Iscovesco) in its new
formulation and packaging. MATERIAL AND METHODS: This randomized, crossed, simple
blind study was carried out in 48 volunteer healthy postmenopausal women. The
volunteers applied on one forearm 1.5 mg/day of cutaneous estradiol in the form
of either gel, according to randomized allocation, for four days without free
period between the two therapeutic periods. The application and drying times of
the two gels were measured during the first application; gel subjective women
assessment was collected at the beginning and at the end of the study. RESULTS:
Mean application and drying times with Gel A are significantly reduced, compared
to Gel B (p=0.0259 and p=0.0001, respectively) with drying time 61% shorter;
these data are confirmed by subjective women evaluation. The two gels are not
significantly different regarding several criteria as consistency, ease of
application and sensation of lasting stickiness. However, a significant
difference is found in favour of Gel A on the following items: practicality of
application (p=0.007), ease of penetration (p<0.001), quantity of gel to apply
(p<0.001) after the first application. After four days of administration, a same
significant difference is observed concerning practicality of the gel (p=0.0078),
duration of use (p<0. 001), packaging, women opinion on the gel (p=0.022) and the
product, gel and packaging (p<0.001). At the end of the study, gel A utilization
is considered by women more practical (p=0.001) with an easier application
(p<0.001) and less restricting while applying (p=0.001), compared to Gel B; 72.9%
of women prefer the Gel A and 12. 5% of women prefer the Gel B. CONCLUSION: A
better acceptability of the 0.1% estradiol gel and of its packaging compared to
that of the 0.06% estradiol gel in this new formulation and packaging is observed
in this study.
PMID- 11011284
TI - [In Process Citation]
PMID- 11011283
TI - [Patient information: responsibility of all physicians to provide proof (hospital
as well as private)].
PMID- 11011285
TI - [Breech presentation: delivery].
PMID- 11011298
TI - [MONICA Project. At the heart of the epidemiological question].
PMID- 11011299
TI - Mammographic screening in women with a family history of breast cancer: some
results from the Swedish two-county trial.
AB - BACKGROUND: The objective of this study is to compare the effectiveness of
mammographic screening in women with a family history of breast cancer to those
without. In the invited arm of a randomised trial of breast cancer screening,
data on family history of breast cancer were available on 29.179 women aged 40-74
attending for screening. Among those women, 358 were diagnosed with breast cancer
during the trial. METHODS: Those with and without a family history were compared
with respect to mammographic parenchymal pattern, interval cancer rates, mean
sojourn time and sensitivity of screening. In the 358 cancers, the effect of
family history was estimated on survival, incidence of advanced cancers and their
relationship to screen detection. RESULTS: A significantly higher proportion of
high risk mammographic patterns was observed in association with family history
among women aged 40-49. Interval cancer rates were higher in women with a family
history, and in older women at least, mean sojourn time was shortened in women
with a family history (1.89 years compared to 2.70). Survival was better
(although not significantly so) in cancers in women with a family history
(relative hazard=0.52) independently of detection mode and was significantly
poorer in interval cancers then screen detected cancers (relative hazard=2.72)
independently of family history. Similarly, interval cancers tended to be larger,
and worse malignancy grade in those with and without a family history of breast
cancer. CONCLUSIONS: These results suggest that the policy often adopted of
annual screening for woman aged 40-49, with a family history of breast cancer, is
a reasonable one, and that it may also be necessary to shorten the inter
screening interval to one year in women aged over 50 but with a positive family
history.
PMID- 11011300
TI - [Breast cancer screening and medical consumption].
AB - BACKGROUND: The use of general health services by women targeted by breast cancer
screening campaigns, and its variations, are poorly known. A survey has been
undertaken during one of these campaigns in a britton department. This study
aimed at pointing out possible differences in use of general health services:
search for an overuse by women whose screening resulted positive/negative, in
relation to women whose screening resulted full negative; search for an overuse
by women having participated, in relation to women within the age range of the
screening campaign and not having wished to participate. METHODS: Three groups of
women, aged 50 to 69 years, free of breast cancer, were compared. A random sample
was drawn in each group, weighing for age in group D0. Inclusion of cases was
undertaken between January 1995 (beginning of the screening campaign) and June
1996. Use of health services was recorded during the six months following the
first screening test, using the health insurance services data. Expenses related
to inpatient care were not recorded. RESULTS: The structure of age of the three
groups was comparable. The proportion of women having requested no reimbursement
was identical between the groups D+ and D-. For the D+ group, the average cost
was 4,246 Francs per woman. It dropped to 3,871 Francs after deduction of
expenses related to additional medical examinations following the finding of a
positive screening test. It was 5% higher than the average cost in the D- group
(3,698 Francs). The cost varied a great deal within each group and the
differences observed between the groups were not statistically significant The
proportion of women of the D0 group not having requested any reimbursement was
significantly lower than those of the groups D- and D+, overall, and for the
majority of the categories of expenditure. CONCLUSION: The result of the
screening does not induce significant variation of use of general health
services, apart from the expenses induced by the invalidation of the positive
result. The group of women not having participated in screening includes a
stronger proportion of both low and higher health services users.
PMID- 11011301
TI - [Personal exposure to fine particles (PM 2.5) in the Grenoble population:
European EXPOLIS study].
AB - BACKGROUND: The aim of this article is to describe PM(2.5) personal exposures
within the Grenoble population and to identify the implications of such
measurements on epidemiological or risk assessment studies of air quality.
METHODS: Non smoking adult volunteers, selected in summer 1996 (n=40), in winter
1997 (n=40) and in summer 1998 (n=20), carried a case containing 2 PM(2.5)
personal monitors. One of the monitors was running continuously for 48h.
(cumulative exposures), the other one was running only while indoors (indoor
exposure). PM(2.5) masses were determined by reflectometry (black smoke method)
and by deionised weighting (Mettler MT5 micro-balance; gravimetric method).
RESULTS: Cumulative PM(2.5) personal exposures ranged on average from 21.9 in
summer to 36.7 microgram/m(3) in winter (arithmetic mean), using the gravimetric
results; the dispersion of these personal exposures was greatest in winter
(s.d.=23.1 microgram/m(3)) than in summer (s.d.=10.4 microgram/m(3)). There was a
good correlation (R=0.7) between the reflectometry and weighting results in
winter, but not in summer. Outdoor personal exposures, determined by difference
between the cumulated and indoor masses, were slightly higher than the cumulative
personal exposures: the geometric means was 49.6 microgram/m(3) (geometric
standard deviation=2.7 microgram/m(3)) in summer and 55.1 microgram/m(3) (3.7
microgram/m(3)) in winter (gravimetric results). Due to these greater outdoor
concentrations, the fraction of outdoor exposure was high (25%) relative to the
small amount of time spent outdoors (less than 10%). CONCLUSION: These
descriptive data, consistent with the literature, show the importance of
"expology" studies aiming at characterizing PM(2.5) personal measurements across
the year. This would lead, in the future, to optimizing the use of "ecological"
estimates of exposures from ambient air concentrations provided by the ambient
air quality networks, for the characterization of exposure in epidemiological or
risk assessment studies.
PMID- 11011302
TI - [Psychosocial distress and its moderating factors in patients living in
precarious socioeconomic conditions consulting in a preventive health and social
work center].
AB - BACKGROUND: The effects of a precarious socioeconomic condition on mental health
have already been widely described. Nevertheless, sociodemographic, biographical,
and mainly psychological determinants of psychosocial distress in these
populations are still incompletely known. METHODS: 2315 consecutive subjects,
aged 16 to 59, consulting for a free work-up in a preventive health center
supported by the National French Health Insurance system, were invited to fill
out a series of questionnaires, mainly the GHQ-28 (psychosocial distress), the
LOT (dispositional optimism) and the WCCL (coping mechanisms). Socioeconomic and
administrative criteria were adopted to define populations living in precarious
conditions. RESULTS: A total of 78.9% complete records could be analyzed: 55% of
the studied population constituted the precarious condition group (44.5% males
and 55.5% females; mean age 36.2+/-11). This group was characterized by higher
psychosocial distress and higher sub-scores of anxiety, social dysfunction and
depression, but not somatisation, as well as by increased emotion focused coping
and impaired optimism. Globally, GHQ score was positively correlated with emotion
focused coping (r=0.36) and negatively with problem focused coping (r=-0.17) and
with optimism (r=-0.39). In a multivariate analysis a set of 9 independent
variables explained 38% of GHQ-28 total variance: perceived stress, optimism,
emotion focused coping, problem focused coping, age, educational degree,
precariousness, money problems and parental quarrels during youth. Introducing
precariousness in the model constituted of the set of the remaining variables
could explain only 2% of additional variance. CONCLUSION: These results confirm
the presence of higher levels of psychosocial distress in subjects living in
precarious conditions and underline the moderating role of several psychological
variables. They could guide support interventions aimed at helping subjects
living in precarious conditions, focused on enhancing their coping resources.
PMID- 11011303
TI - [Two years follow-up of a heroin users cohort treated with high dosage
buprenorphine. Results of the SPESUB study (pharmacoepidemiologic follow-up of
general practice Subutex)].
AB - BACKGROUND: Since February 1996, French GPs are allowed to prescribe high dosage
buprenorphine for maintenance treatment of major opioid drug addiction. A
prospective cohort of major opioid addicts was initiated in order to assess
patient outcomes: follow-up, retention rate in treatment, drug use, intravenous
injection and social situation evolution. METHODS: Each GP, known to be involved
in drug user management, had to include the first 10 opioid drug addict patients
to whom he prescribed high dosage buprenorphine, with a maximum inclusion period
of 3 months. Patients were followed up for two years and a regular standardized
information was collected (usual data on drug users and prescription modalities).
RESULTS: Between May and July 1996, 919 patients (664 men and 255 women, mean
age: 30 years) were included by 101 GPs. They had a long and serious history of
drug addiction, important parallel consumption of cocaine, codeine and other
illicit drugs and psychiatric problems (28% of definite problems and 45% of
probable) and frequent hepatic conditions (hepatitis B: 23%, hepatitis C: 21%).
Two years later, 55% of patients were still followed-up by the same GP and an
additional 12% were followed by another GP or in a health care service
(hospitalized or receiving methadone in a specialized centre). 13% were not
followed, but GPs were able to describe their situation. 8% had been included by
GPs who had dropped the study. Finally, 12% of patients were lost to follow-up.
Among the 508 patients still followed-up by the same GP after 2 years, the
substitution treatment rate was 84%. The dosage bracket had widened (inclusion:
mean dosage=7.8 mg +/-4.5, minimum=0.8, maximum=28, median=8; after 2 years:
mean=7.6 mg +/-5.4, minimum=0.4, maximum=28, median=8) and the duration of the
prescription and dispensing had increased. Declaration of heroin intake in the
previous month had fell from 40% to 11% and declaration of drug intake from 53%
to 20%. Social situation had improved on average (housing conditions and work).
There were 12 seroconversions for hepatitis B, 21 for hepatitis C and 4 for HIV.
14% of patients had declared intravenous injection of high dosage buprenorphine
in the previous month. CONCLUSION: After two years of follow-up, 55% of patients
were still followed-up by the same GP and an additional 12% was followed by
another GP or in a health care service. Among patients still followed up by the
same GP, a reduction of drug related harm (seroconversions for hepatitis B,
hepatitis C and HIV) was observed.
PMID- 11011305
TI - [Modeling incomplete observations].
AB - Incomplete observations, common in epidemiology as in many other fields, lead to
problems of bias, precision and power. Using a simple example with 3 binary
variables, we discuss situations where the observed odds ratio is biased. We
present and compare the main strategies of analysis: complete observations
modeling, missing data indicator, weighted analysis, simple imputation, multiple
imputation, selection models, shared variable models.
PMID- 11011306
TI - [Lot quality assurance sampling: methods and applications in public health].
AB - Lot Quality Assurance Sampling (LQAS), developed to meet industrial quality
control needs, has been applied to health surveys. The WHO used this method to
assess immunization coverage. The sampling strategy was developed to classify
lots as acceptable or unacceptable. Lot sampling is an efficient, simple and time
efficient procedure for quality assurance. Under certain conditions, efficiency
can be improved with double sampling. We describe the method and its theoretical
basis and illustrate applications of LQAS in epidemiological surveillance and
quality control of medical records. The advantages and disadvantages of this
method are presented.
PMID- 11011304
TI - [Occupational exposure to organic solvents and pregnancy. Review of current
epidemiologic knowledge].
AB - The findings and methodological issues of recent epidemiological studies (1989
1999) on adverse developmental effects of maternal occupational exposure to
organic solvents are reviewed. Several studies suggest the possibility of a
moderate increase in the risk of spontaneous abortion and congenital
malformations, especially facial clefts, associated with maternal exposure to
solvents. A common methodological weakness of these studies is the inaccuracy of
data on exposures. Positive findings encourage further epidemiological studies of
high-quality design and use of protective measures to minimize exposure to these
agents from the preconceptional period to the end of pregnancy.
PMID- 11011307
TI - [Cardiovascular risk factors among school children in Sousse, Tunisia].
PMID- 11011308
TI - Genetics of coronary heart disease: current understanding and future prospects.
PMID- 11011309
TI - Recommendations for national and local regulatory authorities concerning research
in genetic markers of disease.
PMID- 11011310
TI - Ethical and legal issues in genetic testing to predict risk of heart disease.
PMID- 11011311
TI - Genetics of coronary heart disease: current knowledge and research principles.
PMID- 11011312
TI - Left atrial enlargement and atrial fibrillation.
PMID- 11011314
TI - Algorithms or nomograms for the busy physician?
PMID- 11011316
TI - Role of salt in hypertensive left venticular diastolic function.
PMID- 11011318
TI - Discrepancy between noninvasive and invasive measurements of MVA after BMC.
PMID- 11011319
TI - Aspirin for the treatment of pulmonary embolism: vasoconstriction versus physical
obstruction.
PMID- 11011321
TI - Genetic approaches for the investigation of genes associated with coronary heart
disease.
PMID- 11011320
TI - Parasympathetic dysfunction as a risk factor in myocardial infarction: what is
the treatment?
PMID- 11011322
TI - Genetic analysis for common complex disease.
PMID- 11011323
TI - Genetic susceptibility to cardiovascular diseases.
PMID- 11011324
TI - Genetics, genomics, proteomics: what is a cardiologist to do?
PMID- 11011325
TI - The mode selection trial (MOST) in sinus node dysfunction: design, rationale, and
baseline characteristics of the first 1000 patients.
AB - BACKGROUND: More than 200,000 permanent pacemakers will be implanted in the
United States in 2000 at a cost of more than $2 billion. Sick sinus syndrome
(SSS) will likely account for approximately half of all cases necessitating
implantation. Pacemaker technology permits the selection of ventricular (single
chamber) or dual-chamber devices. However, clinical and outcomes data are
inadequate to support a clear recommendation that one or the other type of device
be used. METHODS: The Mode Selection Trial (MOST) is a single-blind study
supported by the National Heart, Lung, and Blood Institute designed to enroll
2000 patients with SSS. All patients will receive a DDDR pacemaker programmed to
VVIR or DDDR before implantation. The average time of follow-up will be 3 years.
MOST has a >90% power to detect a 25% reduction in the primary end point-nonfatal
stroke or total (all cause) mortality-in the DDDR-treated group. Secondary end
points will include health-related quality of life and cost effectiveness, atrial
fibrillation, and development of pacemaker syndrome. Prespecified subgroups for
analysis will include women and the elderly. Enrollment was completed in October
1999, with a total of 2010 patients. RESULTS: The median age of the first 1000
enrolled patients is 74 years, with 25% of patients 80 years or older. Women
comprise 49%, and 17% are nonwhite, predominantly black (13%). Before pacemaker
implantation, 22% of patients reported a history of congestive heart failure, 11%
coronary angioplasty, and 25% coronary bypass surgery. Supraventricular
tachycardia including atrial fibrillation was present in 53% of patients. A prior
stroke was reported by 12%. Antiarrhythmic therapy was in use in 18% of patients.
CONCLUSIONS: MOST will fill the clinical need for carefully designed prospective
studies to define the benefits of dual-chamber versus single-chamber ventricular
pacing in patients with SSS. The MOST population is typical of the overall
pacemaker population in the United States. Thus the final results of MOST should
be clinically generalizable.
PMID- 11011326
TI - Extending the useful life of clinical trials.
PMID- 11011327
TI - Detection of threatening atherosclerotic plaque: technologic advancement and
opportunities.
PMID- 11011328
TI - Projected long-term costs of coronary stenting in multivessel coronary disease
based on the experience of the Bypass Angioplasty Revascularization Investigation
(BARI).
AB - BACKGROUND: Stents are now used in the majority of percutaneous coronary
revascularization procedures. It is not clear whether the higher initial cost of
stenting is later repaid by reducing costly complications and repeat
revascularization procedures, especially for patients with multivessel disease.
METHODS: To project the long-term costs of using coronary stents, angioplasty, or
bypass surgery to treat patients with multivessel coronary artery disease, we
developed a decision model based on the outcomes documented in the Bypass
Angioplasty Revascularization Investigation (BARI) randomized trial of coronary
artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty
(PTCA). We studied 2 clinical strategies: provisional stenting of suboptimal PTCA
results and primary stenting of all angiographically eligible lesions. The cost
of CABG was also updated to reflect contemporary practice. RESULTS: Provisional
stenting had lower projected costs over a 4-year period than either traditional
PTCA (-$1742, or -3.4%) or contemporary CABG (-$832, or -1.7%), mostly because of
reductions in emergency CABG after PTCA. In contrast, primary stenting had higher
projected costs over a 4-year period than either PTCA (+$333, or +0. 7%) or
contemporary CABG (+$1243, or +2.5%), mainly because of the higher initial
procedure costs. These results were not substantially altered when we
systematically varied the key parameters of the models in 1-way and 2-way
sensitivity analyses. CONCLUSIONS: A primary stenting strategy in patients with
multivessel disease has higher projected long-term costs than CABG. In contrast,
a provisional stenting strategy in multivessel disease has lower projected costs
than either PTCA or CABG.
PMID- 11011329
TI - Tissue characterization of atherosclerotic plaques by intravascular ultrasound
radiofrequency signal analysis: an in vitro study of human coronary arteries.
AB - BACKGROUND: Conventional gray-scale images of intravascular ultrasound (IVUS)
cannot accurately differentiate histologic subtypes of sonolucent coronary
plaques with or without a lipid core. METHODS: We analyzed radiofrequency signals
obtained in vitro from 24 regions of interest (ROI) of noncalcified (sonolucent)
plaques in 10 atherosclerotic coronary artery specimens pressure-fixed by
formalin. Radiofrequency signals were sampled with a 30-MHz IVUS catheter and
digitized at 500 MHz in 8-bit resolution. The ROIs were histologically
categorized into 12 plaques with a lipid core and 12 plaques without it.
Integrated backscatter and statistical parameters of the radiofrequency envelope
(mean/SD ratio [MSR], skewness, and kurtosis) within the ROI were calculated
offline, and their ability to detect a lipid core was compared with visual
analysis of the IVUS video images. In the group with lipid cores, percent area of
a lipid core in each ROI was measured in a digitized histologic image by a
computerized planimeter. RESULTS: Sensitivity and specificity of MSR, skewness,
and kurtosis for lipid core detection were substantially greater than visual
video image analysis (83.3% and 91.7%, 100% and 91.7%, 100% and 91.7% vs 53.3%
and 71.7%). Furthermore, the parameters of integrated backscatter, MSR, skewness,
and kurtosis were significantly correlated to percent of core area (r = -0.64,
0.73, 0.78, and 0.63, respectively; P<.05). CONCLUSIONS: Compared with IVUS video
images, the parameters of radiofrequency signal analysis may be used to aid in
more accurate detection and quantitative evaluation of a lipid core, which is one
of the major factors of a vulnerable coronary plaque.
PMID- 11011330
TI - Cardiac structure and function in fetuses of mothers infected with HIV: the
prospective PCHIV multicenter study.
AB - BACKGROUND: This study was designed to determine if vertically transmitted HIV
infection and maternal infection with HIV are associated with altered
cardiovascular structure and function in utero. METHODS: Fetal echocardiography
was performed in 173 fetuses of 169 HIV-infected mothers (mean gestational age,
33.0 weeks; SD = 3.7 weeks) at 5 centers. Biparietal diameter, femur length,
cardiovascular dimensions, and Doppler velocities through atrioventricular and
semilunar valves and the umbilical artery were measured. Measurements were
converted to z scores based on published normal data. RESULTS: Fetuses determined
after birth to be HIV-infected had similar echocardiographic findings as fetuses
later determined to be HIV-uninfected except for slightly smaller left
ventricular diastolic dimensions (P =.01). The femur length (P =.03) was also
smaller in the fetuses postnatally identified as HIV-infected. Differences in
cardiovascular dimensions and Doppler velocities were identified between fetuses
of HIV-infected women and previously published normal fetal data. The reason for
the differences may be a result of maternal HIV infection, maternal risk factors,
or selection bias in the external control data. CONCLUSIONS: Vertically
transmitted HIV infection may be associated with reduced left ventricular size
but not with altered cardiac function in utero. Fetuses of HIV-infected mothers
may have abnormal cardiovascular structure and function and increased placental
vascular resistance, regardless of whether the fetuses are subsequently found to
be infected with HIV.
PMID- 11011331
TI - Misrepresentation of left ventricular contractile function by endocardial
indexes: clinical implications after coarctation repair.
AB - BACKGROUND: Endocardial function indexes overestimate myocardial fiber
shortening, a geometric effect proportional to wall thickness. We hypothesized
that elevated endocardial indexes of left ventricular contractile function after
repair of isolated coarctation of the aorta could be related to this effect.
METHODS: Chamber dimensions and wall thickness were measured from 59
echocardiograms in 57 patients aged 1.2 to 32 years, 8.5 +/- 5.6 years after
coarctation repair, and in 305 normal controls aged 1 to 35 years. Midwall and
endocardial shortening indexes and end-systolic fiber stress were calculated. The
stress-velocity index (SVI), a load-independent index of contractility, was
derived from these variables. All values were expressed as z scores. RESULTS:
After coarctation repair, the midwall-derived SVI was elevated, but significantly
less so than the endocardial-derived SVI (0.6 +/- 1.6 vs 1.3 +/- 2.6; P =.01).
The endocardial-derived SVI correlated with the end-systolic thickness/dimension
ratio (P <.0001), but the midwall-derived SVI did not. There was no linear
relation between the midwall-derived SVI and the residual blood pressure
gradient. The mean midwall-derived SVI was higher compared with the normal
population in those with a minor residual blood pressure gradient (=15 mm Hg)
and in those with more significant obstruction (>15 mm Hg), but this achieved
statistical significance only in the latter group (0.5 +/- 1.6, P =.08; and 0.8
+/- 1.7, P =.03, respectively). CONCLUSIONS: Endocardial indexes of function and
contractility overestimate fiber shortening after coarctation repair.
Nevertheless, midwall shortening indexes demonstrate enhanced contractility,
particularly in those with residual coarctation.
PMID- 11011332
TI - Evaluation of left ventricular volumes and ejection fraction with a
nonfluoroscopic endoventricular three-dimensional mapping technique.
AB - BACKGROUND: Recently, a novel nonfluoroscopic 3-dimensional electromechanical
mapping technique was introduced in the clinical arena. Although initial in vitro
and in vivo studies suggested the reliability of the system in volumetric and
hemodynamic evaluation of the left ventricle, no validation in human beings has
been performed. METHODS: A nonfluoroscopic electromechanical mapping (NOGA,
Biosense-Webster) procedure was performed in 44 patients. All patients received a
contrast left ventriculogram during the same session. Volumetric (end-diastolic
[EDV] and end-systolic volumes [ESV]) and hemodynamic (left ventricular ejection
fraction [LVEF] and stroke volume) parameters of both systems were compared.
RESULTS: Two uncomplicated pericardial effusions occurred with the first
generation mapping catheters. No procedural complications were noted with the new
generation mapping catheters. Significant correlations were found between mapping
derived and ventriculography-based measurements for both ESV (r = 0.67, P <.001)
and LVEF (r = 0.78, P <.001). Absolute volumes, however, were only comparable for
ESV (46.6 +/- 25.3 mL vs 48.8 +/- 37.0 mL, respectively; P =.13) but differed
greatly for LVEF (35% +/- 13% vs 65% +/- 19%, respectively; P <.001), EDV (69.1
+/- 28.6 mL vs 125.9 +/- 53.4 mL, respectively; P <.001) and stroke volume (22.4
+/- 9.9 mL vs 77.1 +/- 33.7 respirations; P <.001). Moreover, Bland-Altman
analysis showed the clinical noninterchangeability between these techniques for
the measurement of hemodynamic parameters. CONCLUSION: Measurement of hemodynamic
parameters with nonfluoroscopic mapping of the left ventricle is feasible and
safe. The system provides data that strongly correlate but that are in clinical
disagreement with angiographic data. Therefore the interchangeability of these
techniques may be questioned.
PMID- 11011333
TI - Abciximab provides cost-effective survival advantage in high-volume
interventional practice.
AB - BACKGROUND: Placebo-controlled randomized trials of platelet glycoprotein (GP)
IIb/IIIa blockade during percutaneous coronary intervention have demonstrated
efficacy of these agents for reducing the risk of periprocedural ischemic events.
However, cost-effectiveness of this adjunctive pharmacotherapy has been
scrutinized. Extrapolation of cost-efficacy observations from clinical trials to
"real world" interventional practice is problematic. METHODS: Consecutive
percutaneous coronary interventions (n = 1472) performed by Ohio Heart Health
Center operators at The Christ Hospital, Cincinnati, Ohio, in 1997 were analyzed
for procedural and long-term (6-month) outcomes and charges. Observations on cost
and efficacy (survival) were adjusted for nonrandomized abciximab allocation by
means of "propensity scoring" methods. RESULTS: Abciximab therapy was associated
with a survival advantage to 6 months after percutaneous coronary intervention.
The average reduction in mortality rate at 6 months was 3.4% (unadjusted) and
4.9% when adjusted for nonrandomization. The average charge increment to 6 months
was $1512 (unadjusted) and $950 when adjusted for nonrandomization. Patients
deriving the greatest reduction in mortality rates also had a reduction in total
cardiovascular charges to 6 months. Distinguishing demographics of this
population included multivessel coronary intervention, coronary stent deployment,
intervention within 1 week of myocardial infarction, and lower left ventricular
ejection fraction. The average cost per life-year gained in this study was $2875
for all patients (unadjusted) and $1243 when adjusted for nonrandomization.
CONCLUSIONS: Abciximab provides a cost-effective survival advantage in high
volume interventional practice that compares favorably with currently accepted
standards. Clinical and procedural demographics associated with increased cost
effectiveness included multivessel coronary intervention, stent deployment,
recent (<1 week) myocardial infarction, and impaired left ventricular function.
PMID- 11011334
TI - Ventricular dilation after anterior ST-elevation myocardial infarction in the
thrombolytic era.
AB - BACKGROUND: The aim of this work was to study changes in end-diastolic volume 6
months after Q-wave and non-Q-wave anterior ST-elevation myocardial infarction by
echocardiography. Ventricular dilation after anterior Q-wave myocardial
infarction is well-recognized. However, there is a dearth of information about
the natural history of ventricular volumes after non-Q-wave myocardial
infarction. METHODS: One hundred ninety patients receiving thrombolytic therapy
after anterior ST-elevation myocardial infarction were studied. All patients had
2D echocardiograms and 12-lead electrocardiograms recorded within 24 hours of
symptoms and at 3, 42, and 180 days later. In addition, a further
electrocardiogram was recorded on day 7 to assess patients for the presence of Q
waves. Peak creatine kinase over the first 3 days of admission was recorded. End
diastolic volume index was the study end point. RESULTS: Peak creatine kinase was
strongly associated with ventricular dilation in both groups (P <.001). Mean end
diastolic volume in the Q-wave group increased significantly from day 1 to 6
months (P <.05) but did not alter after non-Q-wave infarction. However, when
patients were selected on predefined criteria for significant change in
ventricular dilation (>10 mL/m(2)), then 35% of those with and 15% of those
without Q waves fell into this category. Within this group, the increase in end
diastolic volume followed a similar pattern, with the maximum percentage increase
occurring between day 1 and 6 weeks. CONCLUSIONS: In the postthrombolytic group
of anterior ST-elevation myocardial infarction, a minority of patients without Q
wave development also undergo significant ventricular dilation.
PMID- 11011335
TI - Renal endothelin in heart failure and its relation to sodium excretion.
AB - BACKGROUND: Recent studies have shown that endothelin-1 (ET-1) antagonists
increase sodium excretion and improve renal blood flow in experimental heart
failure (HF). However, despite a number of investigations that have reported a
significant increase in ET-1 plasma levels in patients with HF, it is still not
known whether increased renal synthesis and urinary excretion of ET-1 occur. Our
aim was to investigate renal ET-1 formation and its relation to sodium excretion
in patients with HF. METHODS: One hundred forty-seven patients with HF,
subdivided according to New York Heart Association (NYHA) functional classes, and
28 healthy controls were studied. ET-1 and big ET-1 were measured in plasma and
in 24-hour urine by radioimmunoassay. Atrial and brain natriuretic peptide,
arginine vasopressin, plasma renin activity, and hemodynamic variables were also
investigated. RESULTS: Urinary ET-1 excretion was already increased in NYHA class
II patients (P <.001 vs controls), whereas plasma ET-1 increased only in NYHA
class III and IV patients (P <.001). In the 71 subjects who were not receiving
diuretic treatment, urinary ET-1 was selected as the strongest predictor of
sodium excretion by multivariate stepwise analysis. CONCLUSIONS: Urinary ET-1
excretion increases in an earlier phase of HF than plasma ET-1 and appears to be
closely correlated with sodium excretion, indicating renal ET-1 is a target for
ET-1 antagonists in patients with HF.
PMID- 11011336
TI - Efficacy, safety, and effects on quality of life of
bisoprolol/hydrochlorothiazide versus amlodipine in elderly patients with
systolic hypertension.
AB - BACKGROUND: Several studies have shown the benefits of antihypertensive treatment
in elderly patients in terms of cardiovascular morbidity and mortality rate
reduction. Low-dose drug combinations may be of interest in treating older
subjects. A randomized, multicenter, double-blind, parallel group study was
conducted to compare the efficacy and safety of bisoprolol 2.5
mg/hydrochlorothiazide 6.25 mg (n = 84) to amlodipine 5 mg (n = 80) in isolated
systolic hypertension in patients older than 60 years. METHODS: After a 2- to 4
week placebo washout period, both drugs were administered once daily and taken
for 12 weeks. Blood pressure was measured 24 hours after treatment
administration. RESULTS: Systolic and diastolic blood pressure changes from
baseline to week 12 were similar for both the bisoprolol and amlodipine groups (
20. 0/-4.5 mm Hg and -19.6/-2.4 mm Hg, respectively). Overall adverse events for
bisoprolol and amlodipine were 39% and 40%, respectively. Changes in quality of
life scores were +2.5 for bisoprolol and +3.2 for amlodipine, with a positive
change indicating improvement. CONCLUSIONS: This study demonstrates comparable
efficacy and tolerability of bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg and
amlodipine 5 mg. The low-dose combination of bisoprolol and hydrochlorothiazide
may be an appropriate alternative for elderly patients with systolic
hypertension.
PMID- 11011337
TI - Long-term central hemodynamic effects at rest and during exercise of losartan in
essential hypertension.
AB - BACKGROUND: Losartan reduces blood pressure in patients with essential
hypertension, but the long-term central hemodynamic effects at rest and during
exercise are not known. METHODS AND RESULTS: After 8 months of losartan treatment
(50 to 100 mg daily, mean 82 mg), intra-arterial pressure was reduced from
165/102 mm Hg to 145/91 mm Hg at rest and from 193/104 mm Hg to 179/96 mm Hg
during 100 W exercise in 28 patients with essential hypertension. Cardiac index
and heart rate remained unchanged, but total peripheral resistance index was
reduced 12% to 15%. Stroke index was unchanged at rest but increased 7% to 9%
during exercise. Twenty-four-hour ambulatory blood pressure was reduced 10% to
13%. Left ventricular mass was reduced 27% in patients with left ventricular
hypertrophy (n = 18). CONCLUSION: Losartan lowers blood pressure by reducing
total peripheral resistance at rest and during exercise but cardiac pump function
is unchanged or slightly improved. In patients with left ventricular hypertrophy,
losartan induces a sizeable reduction in left ventricular mass.
PMID- 11011338
TI - Effect of niacin, warfarin, and antioxidant therapy on coagulation parameters in
patients with peripheral arterial disease in the Arterial Disease Multiple
Intervention Trial (ADMIT).
AB - BACKGROUND: Patients with peripheral arterial disease (PAD) have high rates of
cardiovascular morbidity and mortality, including that caused by associated
coronary heart disease and cerebrovascular disease. Previous studies have shown
that coagulation parameters are altered in PAD and that altered coagulation may
play a critical role in the susceptibility to cardiovascular complications in
PAD. It is therefore important to assess the effect of secondary prevention
measures on coagulation in patients with PAD. The Arterial Disease Multiple
Intervention Trial (ADMIT), a multicenter, randomized, placebo-controlled trial,
was conducted to determine the feasibility of a combined lipid-modifying,
antioxidant, and antithrombotic treatment regimen in patients with PAD. The
objective of this study was to assess the effect of the ADMIT interventions on
coagulation. METHODS: ADMIT participants were randomly assigned to low-dose
warfarin, niacin, and antioxidant vitamin cocktail or corresponding placebos in a
2 x 2 x 2 factorial design. Specialized coagulation studies were performed in a
subset of 80 ADMIT participants at baseline and after 12 months of treatment.
RESULTS: Low-dose warfarin (1 to 4 mg/d) resulted in a significant decrease in
factor VIIc (P <.001) and in plasma F1.2 (P =.001). Unexpectedly, niacin
treatment also resulted in significant decrease in both fibrinogen (48 mg/dL; P
<.001) and F1.2 (P =.04). von Willebrand factor increased after antioxidant
vitamin treatment (P =.04). CONCLUSIONS: A regimen of low-dose warfarin
effectively modifies coagulation in patients with PAD. Niacin also favorably
modifies fibrinogen and plasma F1.2. Niacin, in addition to its lipid effects,
modifies abnormal coagulation factors that accompany PAD.
PMID- 11011339
TI - Superiority of enoxaparin versus unfractionated heparin for unstable angina/non-Q
wave myocardial infarction regardless of activated partial thromboplastin time.
AB - BACKGROUND: Whether the clinical superiority of enoxaparin versus unfractionated
heparin (UFH) depends on a more stable antithrombotic effect or the proportion of
patients not reaching the therapeutic level with UFH has not been addressed.
METHODS: All patients participating in the Thrombolysis In Myocardial Infarction
11B trial who received UFH and had sufficient activated partial thromboplastin
time (aPTT) data (n = 1893) were compared with patients who received enoxaparin
(n = 1938). Patients receiving UFH were divided into 3 categories depending on
mean aPTT values throughout 48 hours: subtherapeutic, for those in whom the
average aPTT fell below 55 seconds; therapeutic, between 55 and 85 seconds; and
supratherapeutic, longer than 85 seconds. Events and bleeding rates were
determined at 48 hours. RESULTS: A small portion of patients (6. 7%) had a
subtherapeutic average aPTT value (n = 127). Forty-seven percent of patients (n =
891) fell within the therapeutic range, and 46% were in the supratherapeutic
level (n = 875). Event rates were 7. 0% in the UFH group versus 5.4% with
enoxaparin (P =.039). Events rates were higher in every aPTT strata compared with
enoxaparin and statistically significant in the supratherapeutic group (odds
ratio 0.65; 95% confidence interval, 0.47-0.89). Major bleeding rates were 0%,
0.6%, and 0.9% for the subtherapeutic, target, and supratherapeutic strata,
respectively, and 0.8% with enoxaparin. Minor hemorrhages occurred in 5.1% of
patients receiving enoxaparin versus 3.9%, 2%, and 2.3%, respectively, for the
UFH subgroups (P <. 001 for all UFH groups vs enoxaparin). CONCLUSIONS:
Enoxaparin showed a better clinical profile compared with every level of
anticoagulation with UFH. Potential mechanisms for enoxaparin superiority are
stable antithrombotic activity, lack of rebound thrombosis, and intrinsic
superiority.
PMID- 11011340
TI - Effect of delay on racial differences in thrombolysis for acute myocardial
infarction.
AB - OBJECTIVE: To analyze the effect of delay times on racial differences in
thrombolysis for acute myocardial infarction. BACKGROUND: Lower rates of
thrombolytic therapy in blacks with acute myocardial infarction have recently
been reported, but the reasons for this disparity are unknown. We hypothesized
that lower rates of thrombolysis are caused by delay in presentation after
symptom onset. METHODS: From November 1992 through November 1996, consecutive
patients with a first acute myocardial infarction presenting to a large, urban
teaching hospital were prospectively enrolled. Delay times were determined
retrospectively from review of medical records. Patients were prospectively
followed up for in-hospital cardiac events and death. A multivariable regression
model was built to relate presentation times and other variables to thrombolysis
administration. RESULTS: A total of 395 patients were included in the study, of
which 33% were black. Symptom onset to emergency department presentation and door
to-needle times were significantly longer in blacks. Thrombolysis was
administered significantly less often in blacks compared with whites (47% vs 68%,
P =.001). Black race and age above 60 years were independently associated with
delayed presentation and prolonged door-to-needle times. Black race, time to
presentation, and non-Q-wave myocardial infarction were independently associated
with not receiving thrombolysis. In-hospital mortality rates were similar in both
groups. CONCLUSIONS: Blacks presented later than whites for first acute
myocardial infarction. Late arrival strongly influenced the rate of thrombolysis
administration. Lower rates of thrombolysis and prolonged door-to-needle times
were apparent in blacks after adjustment for delay times and other clinical
factors, a finding that merits further investigation.
PMID- 11011341
TI - Adequacy of intracoronary versus intravenous adenosine-induced maximal coronary
hyperemia for fractional flow reserve measurements.
AB - BACKGROUND: Fractional flow reserve (FFR) is a measure of coronary stenosis
severity that is based on pressure measurements obtained at maximal hyperemia.
The most widely used pharmacologic stimulus for maximal coronary hyperemia is
adenosine, administered either as a continuous intravenous (IV) infusion or
intracoronary (IC) bolus. IV adenosine has more side effects and is more costly
than IC adenosine but has a more stable and prolonged hyperemic effect. METHODS:
We compared the efficacy of IC and IV adenosine administration for the
measurement of FFR in a multicenter trial. Fifty-two patients with 60 lesions
underwent determination of FFR with both IV and IC adenosine. IV adenosine was
administered as a continuous infusion at a rate of 140 microgram/kg per minute
until a steady state hyperemia was achieved. IC adenosine boluses were
administered at a dose of 15 to 20 microgram in the right and 18 to 24 microgram
in the left coronary artery. FFR was calculated as the ratio of the distal
coronary pressure (from pressure guide wire) to the aortic pressure (guide
catheter) at maximal hyperemia. RESULTS: A total of 26 left anterior descending,
23 right, 9 left circumflex, and 3 left main coronary arteries were evaluated.
Mean percent stenosis for both groups was 55.8% +/- 23.6% (range 0% to 95%), and
mean FFR was 0.78 +/- 0.15 (range 0.41 to 0.98). There was a strong and linear
correlation between FFR measurements with IV and IC adenosine (R = 0.978, y = 0.
032 + 0.964x, P <.001). The agreement between the 2 sets of measurements was also
high, with a mean difference in FFR of -0.004 +/- 0.03. However, a small random
scatter in both directions of FFR measurements was noted with 5 lesions (8.3%)
where FFR with IC adenosine was higher by 0.05 or more compared with IV
infusions, suggesting a suboptimal hyperemic response in these patients. Changes
in heart rate and blood pressure were significantly higher with IV adenosine. Two
patients with IV, but none with IC adenosine, had severe side effects
(bronchospasm and severe nausea). CONCLUSION: These results suggest that IC
adenosine is equivalent to IV infusion for the determination of FFR in the
majority of patients. However, in a small percentage of cases, coronary hyperemia
was suboptimal with IC adenosine.
PMID- 11011343
TI - Changes in rates of beta-blocker use between 1994 and 1997 among elderly
survivors of acute myocardial infarction.
AB - BACKGROUND: Results of recent studies suggest that beta-blockers are underused by
elderly acute myocardial infarction (AMI) survivors. The goals of this study were
to examine changes in post-AMI beta-blocker use occurring between 1994 and 1997
and to identify factors associated with outpatient use of beta-blockers. METHODS:
Patients included 9534 individuals >/=65 years of age who were enrolled in
Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) and who
survived AMI between 1994 and 1997. With the use of outpatient prescription
claims, beta-blocker usage rates were examined by year, and multivariate logistic
regression was used to identify predictors of beta-blocker use. RESULTS: Post-AMI
beta-blocker use increased from 39.6% in 1994 to 58.6% in 1997. Controlling for
AMI year, individuals who had any prescriptions written by a cardiologist were
more likely to use a beta-blocker than individuals who received all prescriptions
from noncardiologists (odds ratio 1.52, P =.0001). Elderly patients who did not
use beta-blockers tended to have greater severity of illness, non-Q-wave
infarctions, atrial fibrillation, and comorbidities such as congestive heart
failure, chronic obstructive pulmonary disease, and asthma. Use of calcium
channel blockers and diuretics was negatively associated with beta-blocker use,
but persons using lipid-lowering agents were more likely to use beta-blockers.
CONCLUSIONS: Significant improvements in beta-blocker use by elderly AMI
survivors have occurred since 1994. Differences among physician specialties in
beta-blocker prescribing appear to remain. Across all prescriber specialties,
historic contraindications constitute major factors in the choice of post-AMI
therapy. Further efforts should be made to encourage the use of beta-blockers in
elderly survivors of AMI, particularly those with heart failure.
PMID- 11011342
TI - Incidence of left atrial thrombi in patients in sinus rhythm and with a recent
neurologic deficit.
AB - OBJECTIVES: We sought to determine the incidence of left atrial (LA) thrombi in
patients in sinus rhythm (SR) and with a recent neurologic deficit and to analyze
the relation between LA thrombi and LA chamber and appendage function in patients
in SR. METHODS: A prospective study was conducted in 869 consecutive patients.
The study group consisted of 583 patients in SR (67%). The remaining 286 patients
had atrial fibrillation (AF) and served as controls (33%). RESULTS: The incidence
of LA thrombi was significantly higher in patients with AF (n = 39 [14%])
compared with patients in SR (n = 6 [1%]; P <.001). Three of 6 patients with
thrombi in SR had mitral stenosis, 1 patient had aortic stenosis, 1 patient had
coronary artery disease, and another patient had a cardiomyopathy. Of the
patients with detected thrombi, those in SR did not receive anticoagulation,
whereas those with AF did in 18 cases. Patients with thrombi in SR and with AF
did not significantly differ in LA diameter (5.1 +/- 0.8 cm vs 4.8 +/- 0.7 cm;
95% confidence interval [CI], -0.78 to 0.45), left ventricular ejection fraction
(46% +/- 13% vs 42% +/- 15%; 95% CI, -18.7 to 7.4), LA appendage area (5.8 +/-
2.7 cm(2) vs 6.7 +/- 3.2 cm(2); 95% CI, -1.9 to 3.6), peak emptying velocity of
the LA appendage (0.19 +/- 0.08 m/s vs 0.17 +/- 0.07 m/s; 95% CI, -0.08 to 0.04),
or LA spontaneous echo contrast (3. 5 +/- 0.6 vs 3.9 +/- 0.5; 95% CI, -0.06 to
0.45). CONCLUSIONS: LA appendage thrombi are an infrequent cause of
thromboembolism in patients in SR and are associated either with mitral valve
disease or LA chamber and appendage dysfunction. Routine transesophageal
echocardiography for the exclusion of LA thrombi is not recommended in patients
in SR without underlying heart disease and normal LA function as assessed by
transthoracic echocardiography.
PMID- 11011344
TI - Twenty-four-hour autonomic nervous function in sustained and "white coat"
hypertension.
AB - BACKGROUND: It is unknown whether "white coat" hypertension, also known as
isolated clinic hypertension, shares similarities in pathophysiologic background
with sustained hypertension. Therefore we evaluated 24-hour autonomic nervous
function in sustained and white coat hypertension. METHODS: We selected 12
patients with sustained hypertension (clinic blood pressure >/=140/90 mm Hg and
daytime blood pressure >135/85 mm Hg) and 12 patients with white coat
hypertension (clinic blood pressure >/=140/90 mm Hg and daytime blood pressure
<135/85 mm Hg) from patients undergoing ambulatory blood pressure monitoring and
12 normotensives for study inclusion. Groups were matched for age, sex, and body
mass index and had similar dietary pattern and occupational status (civil
servants with sedentary jobs). Subjects underwent noninvasive 24-hour monitoring
of blood pressure, R-R interval of the electrocardiogram, body position, activity
rate, and ambient temperature. Power spectral analysis of R-R intervals was
performed with an autoregressive model to obtain the low-frequency component, the
high-frequency component, and their ratio. Subjects also collected 24-hour urine
samples for examination of norepinephrine and epinephrine excretion by high
performance liquid chromatography. RESULTS: Work and sleep time, body position,
ambient temperature, and activity were not different among the groups. Daytime,
nighttime, and 24-hour low-frequency/high-frequency ratios were significantly
higher in patients with sustained hypertension than in patients with white coat
hypertension (3.4 +/- 0.45 vs 2.65 +/- 0.45, 2.35 +/- 0.60 vs 1. 82 +/- 0.45, and
3.04 +/- 0.45 vs 2.4 +/- 0.35, respectively, P <. 05). Urinary norepinephrine
excretion (53 +/- 12 microg vs 29.5 +/- 6 microg; P <.05) and vanillylmandelic
acid excretion (4.45 +/- 0.6 mg vs 3.1 +/- 0.55 mg; P <.05) during the 24 hours
were significantly higher in patients with sustained hypertension than in those
with white coat hypertension. There was no difference between those with white
coat hypertension and normotensives concerning the aforementioned parameters.
CONCLUSIONS: Our findings indicate whole-day sympathetic overactivity in
sustained hypertension but not in white coat hypertension, suggesting that these
conditions show some differences in pathophysiologic background.
PMID- 11011345
TI - Sex differences on the electrocardiographic pattern of cardiac repolarization:
possible role of testosterone.
AB - BACKGROUND: Cardiac repolarization has been shown to be shorter and faster in men
compared with women. In this study, we examined the electrocardiographic pattern
of repolarization in patients with abnormal plasma levels of testosterone to gain
insight into the role that this hormone plays in modulating repolarization.
METHODS AND RESULTS: Repolarization was measured in 27 castrated men, 26 women
with virilization, and 53 control subjects pair-matched for age and sex.
Repolarization in castrated men was slower and longer than that of normal men.
Women with virilization exhibited a shorter and faster repolarization than normal
women and castrated men. These differences are the opposite of those found in the
normal population. Finally, the changes observed in castrated men may be reverted
by testosterone. CONCLUSIONS: We conclude that testosterone plays an important
role in modulating cardiac repolarization.
PMID- 11011346
TI - Endothelium-dependent responses in patients with hypercholesterolemic coronary
artery disease under the effects of simvastatin and enalapril, either separately
or combined.
AB - BACKGROUND: Endothelial dysfunction is an early event in atherosclerotic disease
that precedes clinical manifestations and complications. The noninvasive
assessment of endothelial function in patients with risk factors undergoing
clinical treatment is an important medical advance. In this setting, altered
endothelial function in patients with coronary hypercholesterolemia and its
modifications by treatment with enalapril and simvastatin, either separately or
in combination, was assessed in the brachial artery in a randomized, double
blind, 2-period crossover study. METHODS: Thirty-eight patients were separated in
2 groups. Group 1 (18 patients, 3 female, mean age 63 +/- 6.0 years) received
simvastatin 10 mg/d for 8 weeks and simvastatin plus enalapril 5 mg/d for another
8 weeks. Group 2 (20 patients, 3 female, mean age 64 +/- 5.8 years) received
enalapril 5 mg/d for 8 weeks and enalapril plus simvastatin 10 mg/d for another 8
weeks. All subjects underwent measurements of brachial artery diameter before and
after postischemic hyperemia with high-resolution ultrasound at basal conditions
(control) and under the effects of the drugs at the end of 8 and 16 weeks.
RESULTS: Cholesterol and LDL cholesterol levels significantly decreased with
simvastatin treatment alone or with enalapril. Mean baseline arterial diameter
was 5.24 +/- 1.25 mm in group 1 and 4.83 +/- 0.99 mm in group 2 (not
significant). In group 1 after the first 8 weeks, endothelium-dependent
vasodilation significantly increased with simvastatin treatment (control, 4.4%; 8
weeks, 7.6%; P <.001). After 16 weeks with the addition of enalapril, a further
increase in vasodilation was seen (8.6%, P <.05 vs 8 weeks). In group 2, with
enalapril treatment an increase in vasodilation versus control was seen (control,
4.3%; 8 weeks, 5.8%; P <.01). After 16 weeks, with the addition of simvastatin an
additional increase in vasodilation was observed (9.1%, P <.001 vs 8 weeks).
After nitroglycerin, vasodilation in group 1 at control, 8, and 16 weeks was 17%,
17.5%, and 18%, respectively. In group 2, nitroglycerin vasodilation at control,
8, and 16 weeks was 21%, 21%, and 22%, respectively. CONCLUSIONS: Simvastatin
significantly increased the postischemic vasodilator response in patients with
coronary hypercholesterolemia, either as single treatment or added to enalapril.
Similarly, the response was increased by enalapril, either alone or while
simvastatin was being administered. Both drugs improve vasodilation and additive
effects appear to be present.
PMID- 11011347
TI - Cardiac biochemical markers after cardioversion of atrial fibrillation or atrial
flutter.
AB - BACKGROUND: Cardioversion or defibrillation of cardiac arrhythmias is often
necessary in acutely ill cardiac patients. The electrical current may cause
elevation of biochemical markers used to diagnose acute myocardial infarction.
Therefore it is important to find cardiac markers with high specificity for
myocardial necrosis. The purpose of this study was to assess the effects of
elective cardioversion of atrial fibrillation or flutter on troponin T and I
among conventional markers in patients with no evidence of acute ischemia.
METHODS AND RESULTS: Fifty-seven consecutive patients underwent 1 to 4 direct
current shocks (mean cumulative energy 407 J, range 100 to 920 J) under general
anesthesia. At baseline, all had normal troponin levels; 50 patients (mean age 68
years, range 33 to 84 years) had normal cardiac enzymes and were included in the
final analysis. Blood samples were drawn at baseline, and 1 to 2, 6 to 8, and 20
to 24 hours after cardioversion. The troponin levels were unaffected by
cardioversion in all patients, whereas creatine kinase and myoglobin increased
more than 10-fold. Creatine kinase MB mass and aspartate aminotransferase were
above reference limits in 18% and 24% of patients, respectively, 20 to 24 hours
after cardioversion. There was a significant association between elevated
creatine kinase, myoglobin, and creatine kinase MB levels with cumulated energy
delivered as well as when possible confounders such as age and sex were adjusted
for. High international normalized ratio with warfarin use was associated with
increased levels of creatine kinase, aspartate aminotransferase, lactate
dehydrogenase, and myoglobin. CONCLUSIONS: The increase of conventional
biochemical markers after direct current cardioversion is positively associated
with cumulative energy delivered and international normalized ratio (INR) values;
neither influences levels of the cardiac troponins.
PMID- 11011348
TI - Introduction.
PMID- 11011350
TI - Depression and ischemic heart disease.
AB - Major depression is a common comorbidity associated with ischemic heart disease
(IHD). There is growing evidence that psychological stress in general and
depression in particular predispose to cardiovascular disease. Persons who have
mental stress during daily life are at twice the risk of myocardial ischemia, and
patients with post-myocardial infarction depression have higher mortality rates
than nondepressed controls. These data suggest a psychophysiologic mechanism
underlying the vulnerability of depressed patients to IHD. Clinical studies have
demonstrated that depression is associated with a much higher risk of both
cardiovascular morbidity and mortality, which could be caused by platelet
activation. Physicians should maintain a heightened level of clinical suspicion
for depression and depressive disorders in persons with IHD, particularly those
individuals who are recovering from an acute ischemic event, such as myocardial
infarction. Furthermore, depression may complicate the recovery of IHD, but in
most cases depression can be effectively treated with antidepressant agents.
PMID- 11011349
TI - Are platelets the link between depression and ischemic heart disease?
AB - The role of platelets as the link between ischemic heart disease and depression
is reviewed. Platelet function abnormalities, including increased platelet
reactivity, may predispose depressed patients to clotting diatheses and may
explain their vulnerability to cardiovascular disease. Platelet physiologic
characteristics, influences on platelet response, and indicators of platelet
reactivity are discussed. Measurements of platelet activation, secretion, and
aggregation have enabled the study of platelet responses in patients with major
depression. The findings of clinical trials evaluating platelet responses to
antidepressant treatment are described, and recommendations for future studies
are proposed.
PMID- 11011351
TI - Depression as a contributing factor in cerebrovascular disease.
AB - Stroke is a leading cause of morbidity and mortality in the United States.
Physical and psychological impairment from stroke may negatively affect quality
of life. From a psychological perspective, depression, which is common in stroke
patients, may influence functional recovery and possibly mortality after a
stroke. Although somewhat controversial, the risk of poststroke depression may be
related to lesion location, specifically left anterior or left basal ganglia
lesions. Because poststroke depression can affect recovery, treatment with
antidepressants may be warranted. Emerging evidence suggests that nortriptyline
and fluoxetine may be effective; paroxetine, sertraline, and other selective
serotonin reuptake inhibitors have shown efficacy in treating a related
phenomenon known as pathologic crying. The influence of depression on the risk of
stroke has not been extensively studied; however, several epidemiologic studies
raise the possibility that a relation exists. In one study of elderly
individuals, higher depressive symptoms increased the risk of stroke. Many older
individuals who have depression develop later in life have evidence of subtle
cerebrovascular disease. Specifically, silent strokes that do not involve the
sensory or motor parts of the brain are quite common in the elderly population.
Vascular depression is depression that occurs in patients with cerebrovascular or
ischemic changes in the brain. Preliminary evidence indicates that these vascular
changes may be related to atherosclerosis, hypertension, or myocardial
infarction. However, additional studies are needed to gain a better profile of
these patients and to explore potential treatment modalities.
PMID- 11011352
TI - Heart rate variability in depressive and anxiety disorders.
AB - Loss of normal autonomic nervous system control of heart rate and rhythm is an
important risk factor for adverse cardiovascular events. After myocardial
infarction, reduction in beat-to-beat heart rate variability, a measure of
cardiac autonomic innervation by the brain, is a strong predictor of death. With
loss of vagal innervation, as is noted in patients with severe neuropathy and in
heart transplant recipients, there is loss of heart rate variability. It is
speculated that decreased parasympathetic innervation exposes the heart to
unopposed stimulation by sympathetic nerves. Individuals with high hostility
scores and patients with anxiety or depressive disorders have low heart rate
variability and may be at increased risk for cardiovascular death associated with
coronary heart disease and arrhythmias. After myocardial infarction, depressed
patients exhibit higher mortality rates compared with nondepressed patients. Men
with "phobic anxiety," a construct that appears to overlap substantially with
panic disorder, also have higher rates of sudden cardiac death and coronary
artery disease than control populations. The reduction in autonomic nervous
system control to the heart may be one link between psychopathology and heart
disease. Although tricyclic antidepressants reduce heart rate variability, at
least one study has suggested that, in patients with panic disorder, treatment
with the selective serotonin reuptake inhibitor paroxetine normalizes heart rate
variability. Hence there is potential for the treatment of psychiatric disorders
to affect positively the development and course of cardiovascular disease.
PMID- 11011353
TI - Considerations for the use of antidepressants in patients with cardiovascular
disease.
AB - There is convincing evidence that depression can significantly and adversely
affect cardiovascular health and increase mortality rates in patients with
documented ischemic heart disease. It is unknown whether treatment of depression
can reduce the risk of IHD or if treatment can decrease mortality rates after
myocardial infarction. Nonetheless, the available evidence strongly suggests that
depression in patients with cardiovascular disease should be treated. Tricyclic
antidepressants had been considered acceptable for use in patients with ischemic
heart disease until data from the Cardiac Arrhythmia Suppression Trial (CAST)
demonstrated a significantly increased mortality rate after myocardial infarction
in patients treated with type I antiarrhythmics. Because tricyclic
antidepressants are type IA antiarrhythmics, they presumably carry a risk similar
to that of moricizine in patients with ischemic disease. The limited but growing
data available on the use of selective serotonin reuptake inhibitors and
bupropion in patients with cardiac disorders suggest that these agents are safer
antidepressant treatment alternatives. Larger, long-term, randomized, controlled
studies are needed to confirm that selective serotonin reuptake inhibitors are
indeed safe in depressed patients with cardiovascular disease.
PMID- 11011363
TI - [Topical organization of the cat inferior colliculus under conditions of the
simulated sound source motion].
AB - Binaurally presented click trains with gradually changing ITDs were used to
imitate the sound source motion. Focal EP-trains from the cat inferior
colliculus, IC, were recorded, and changing amplitude of the successive EPs
following successive clicks was taken for estimation of the motion effect (ME).
It was shown that a) in 25% of cases the ME depends on the motion direction; b)
the ME is better presented ipsilaterally in respect to the recording point, with
equal dependence on motion velocity both on the left and on the right; c) the ME
phenomenon is connected with prevalence of contralateral afferentation as
compared to the ipsilateral one; d) the ME is connected with inhibitory phenomena
such as binaural suppression of monaural afferentation; e) the ME of the best
amplitude is most pronounced in the ventrolateral area of the IC central nucleus,
its localisation being near to that of the great multipolar neurones, whereas
slightly and moderately pronounced MEs are presented rather uniformly over the
central nucleus like the "basic" neurones are; MEs of different pronouncement are
supposed to depend differently on effectiveness of ipsi- and contralateral
stimulation--in accordance with properties of multipolar and "basic" neurons.
PMID- 11011362
TI - [The role of ventrolateral thalamic nucleus in switching of the descending
influence over to the rat motor activity].
AB - Facilitated influence of preliminary transection of the rat rubrospinal tract on
motor activity and instrumental reflexes recovering after lesion of the red
nucleus was more obvious after a chemical lesion rather than the electrolytic
lesion. This seems to be due to remaining cerebello-thalamic fibres after a
chemical lesion of the red nucleus. A preliminary destruction of the
ventrolateral thalamic nucleus was shown to complicate switching of the motor
activity in the rats with transected rubrospinal tract and lesioned red nucleus.
PMID- 11011364
TI - [Comparison of binaural release from forward masking in animals and humans.
Electrophysiologic study].
AB - The EPs of the inferior colliculus and auditory cortex in anaesthetized guinea
pigs and the long latency auditory EPs in alert humans were studied. The stimuli
consisted of binaurally presented pairs of clicks used as a masker, and the
probe, with a variable time delay between them. The greatest relative differences
between out-of-phase and in-phase probe responses were observed at the beginning
of the recovery course. They averaged as 1.6, 1.5 and 1.4 for the responses of
the inferior colliculus, auditory cortex and long latency potentials, resp., at
the stimuli intensities of 50-65 dB SPL, and then decreased to zero during the
time course of the probe response recovery. Correlation of this parameter with
the stimulus intensity was positive.
PMID- 11011365
TI - [Mechanisms of the otolith signal processing].
AB - A series of current hypotheses of mechanisms of the otolith signals processing
and organization of adaptive responses of the oculomotor system to gravito
sensitive (otolith) inputs are reviewed: the "frequency segregation of the
otolith signals", "gravito-inertial force resolution", "spatio-temporal
transformation of the angular vestibulo-ocular reflex", "inertial processing of
the vestibular signals", "asymmetry of the otolith signals", and their
experimental corroboration.
PMID- 11011368
TI - [Auditory analysis of the sound source approaching and withdrawing:
psychoacoustic and neurophysiological correlates].
AB - The findings seemed to be based on direction and velocity of modelling the radial
sound source shifting in free acoustic field. The threshold and the optimal
parameters of the acoustic model imitating the approaching and withdrawing of the
sound source shifting in silence and under conditions of noise, were established.
A correlation between peak-to-peak amplitudes of the N1-P2 components of auditory
EPs and the imitated direction of the sound shifting, was shown. The role of
different left and right hemispheres' areas in perception of the radial sound
source was analysed. The detector features of the central auditory neurones were
shown as a possible mechanism of estimating the sound source approaching and
withdrawal.
PMID- 11011367
TI - [Disinhibition as a mechanism of tuning of cross-like figures in the visual
cortex neurons].
AB - A discrete neural net was used for simulation of cross-sensitivity in 40% of
neurones of the cat visual cortex' area 17th. It is based on disinhibition of the
end-stopping inhibition in receptive field from the side-disinhibitory zone.
Highly selective or invariant sensitivity of the simulated neurone in respect to
shape and orientation of a cross-like figure was observed under changes of
location, size and weight of the receptive field zones. The disinhibitory
mechanism seems to be critically involved in the selection of the second-order
features of the images in the primary visual cortex.
PMID- 11011366
TI - [Intercellular integration in the central nervous system].
AB - A humoral mechanism of the intercellular communication in the CNS based on
diffusion of neuroactive compounds within the brain extracellular space, was
studied. The leading role of the volume transmission was shown in the early stage
of ontogeny. Structural basis of this mechanism was studied in adult mammals, and
the data on extrasynaptic receptors and release of classical neurotransmitters
into the extracellular space was reviewed.
PMID- 11011369
TI - [Effect of serotonin on isolated cells with the various functionality from the
lamprey spinal cord].
AB - The differential actions of 5-hydroxytryptamine (5-HT) (100 microM) were
investigated on isolated motoneurons, interneurons, and primary sensory neurons
from the lamprey spinal cord using patch-clamp techniques. Application of 5-HT
did not evoke membrane currents in any of the spinal neurons tested (n = 62).
However, in most motoneurons and interneurons (15 of 18), 5-HT produced a small
depolarization (2-6 mV), which was not accompanied by a change in input
resistance. In the remaining motoneurons and interneurons (3 of 18), 5-HT induced
a large depolarization (up to 10-20 mV) and a decrease in input resistance of 20
60%. In most sensory neurons (dorsal sensory cells, DSCs), 5-HT evoked a short
lasting, low-amplitude depolarization, followed by a long-lasting
hyperpolarization of 2-7 mV. The DSCs showed no significant change in input
resistance to 5-HT application (n = 8). Spike afterpolarization were also
differentially modulated by 5-HT. In motoneurons and interneurons, 5-HT decreased
the amplitude of the afterhyperpolarization following the action potential while
increasing the amplitude of the after depolarization. In the DSCs, no significant
effect of 5-HT on spike afterpolarization was observed. 5-HT differentially
modulated the current induced by application of N-methyl-D-aspartate (NMDA). In
motoneurons and interneurons, 5-HT enhanced NMDA-evoked current, while in DSCs, 5
HT decreased this current. These results demonstrate that 5-HT differentially
modulates the activity of functionally different groups of spinal neurons. In
motoneurons and interneurons, 5-HT enhances excitation by inducing depolarization
and decreasing the afterhyperpolatization, while NMDA currents are enhanced.
These effects facilitate the appearance of rhythmic discharges in these cells in
the presence of NMDA. In primary dorsal sensory cells, 5-HT enhances inhibition
by hyperpolarizing the cells and depressing NMDA currents. These differential
effects are presumably mediated by different types of 5-HT receptors on these
classes of spinal neurons.
PMID- 11011370
TI - [Studies of directional sensitivity of neurons in the cat primary auditory
cortex].
AB - A set of impulsive transient signals has been synthesized for earphone delivery
whose waveform and amplitude spectra, measured at the eardrum, mimic those of
sounds arriving from a free-field source. The complete stimulus set forms a
"virtual acoustic space" (VAS) for the cat. VAS stimuli are delivered via
calibrated earphones sealed into the external meatus in cats under barbiturate
anesthesia. Neurons recorded extracellularly in primary (AI) auditory cortex
exhibit sensitivity to the direction of sound in VAS. The aggregation of
effective sound directions forms a virtual space receptive field (VSRF). At about
20 dB above minimal threshold, VSRFs recorded in otherwise quiet and anechoic
space fall into categories based on spatial dimension and location. The size,
shape and location of VSRFs remain stable over many hours of recording and are
found to be shaped by excitatory and inhibitory interactions of activity arriving
from the two ears. Within the VSRF response latency and strength vary
systematically with stimulus direction. In an ensemble of such neurons these
functional gradients provide information about stimulus direction, which closely
accounts for a human listener's spatial acuity. Raising stimulus intensity,
introducing continuous background noise or presenting a conditioning stimulus all
influence the extent of the VSRF but leave intact the gradient structure of the
field. These and other findings suggest that such functional gradients in VSRFs
of ensembles of AI neurons are instrumental in coding sound direction and robust
enough to overcome interference from competing environmental sounds.
PMID- 11011371
TI - [Visual, auditory, and bimodal activity in the banks of the lateral suprasylvian
sulcus in the cat].
AB - In addition to visually driven cells we found within the lateral suprasylvian
visual cortex of cats a considerable number of auditory and/or bimodal cells.
Most of the visually driven cells were direction and orientation selective with
responses that were neither highly stimulus time locked nor very stable. Most of
the auditory responses were also not very stable, had relatively high thresholds
and were readily habituated. Previous studies have suggested that populations of
cells within the lateral suprasylvian area are specialized for the analysis of
optic flow fields. Given that a remarkable proportion of cells within this area
can be also driven by auditory stimuli we hypothesize that the "optic flow" model
may be extended to the bimodal domain rather than restricted to visual clues
only. This, however, remains to be corroborated experimentally.
PMID- 11011372
TI - [Neural mechanisms of sound localization in owls].
AB - Barn owls localize sound by using the interaural time difference of the
horizontal plane and the interaural intensity difference for the vertical plane.
The owl's auditory system possesses the two binaural cues in separate pathways in
the brainstem. Owls use a process similar to cross-correlation to derive
interaural time differences. Convergence of different frequency bands in the
inferior colliculus solves the problems of phase-ambiguity which is inherent in
cross-correlating periodic signals. The two pathways converge in the external
nucleus of the inferior colliculus to give rise to neurons that are selective for
combinations of the two cues. These neurons form a map of auditory space. The map
projects to the optic tectum to form a bimodal map which, in turn, projects to a
motor map for head turning. The visual system calibrates the auditory space map
during ontogeny in which acoustic variables change. In addition to this tectal
pathway, the forebrain can also control the sound-localizing behaviour.
PMID- 11011373
TI - Killer waves on the East coast?
PMID- 11011374
TI - The roots of homicide.
PMID- 11011376
TI - Biology--cell death. One-hit wonder.
PMID- 11011375
TI - Womb wars.
PMID- 11011377
TI - Speech without accountability.
PMID- 11011378
TI - The wireless Web.
PMID- 11011379
TI - The Internet in your hands.
PMID- 11011380
TI - The promise and perils of WAP.
PMID- 11011381
TI - The future is here. Or is it?
PMID- 11011382
TI - The third-generation gap.
PMID- 11011383
TI - Operating on a beating heart.
PMID- 11011385
TI - Animals imitate, too.
PMID- 11011384
TI - The power of memes.
PMID- 11011386
TI - Meme theory oversimplifies how culture changes.
PMID- 11011387
TI - People do more than imitate.
PMID- 11011388
TI - Nabada: the buried city.
PMID- 11011389
TI - Better decisions through science.
PMID- 11011391
TI - Down among the micrograms.
PMID- 11011390
TI - Contact lenses. The hard and the soft.
PMID- 11011392
TI - Million-dollar minesweeper.
PMID- 11011393
TI - Getting high. Booze, dope, metaphysics and other rhapsodic matters.
PMID- 11011394
TI - [Nikolai Vladimirovich Ekk (1849-1908)].
PMID- 11011395
TI - ["Multiple organ failure syndrome". Nature of the concept and correctness of the
nomenclature].
AB - The syndrome principle of studying complex pathological processes is justified if
the key link of the pathogenesis is determined. The multi-organ systemic
dysfunction is due to altered synergism of all visceral functions rather than to
the sum of functional alterations of several organs. The main ideas and
regularities of the synergism as the fundamental theoretical directions determine
the coordination of vital activity and the probability of its disturbance
depending on genetically determined and other factors. Grounds are presented for
the prospects of using the Mandelbroth's fractals and regularities of synergism
in creation of the prognostic dynamic models in the organism's extreme states.
PMID- 11011397
TI - [Strategy of treatment of aortic stenosis complicated by total calcinosis].
AB - The authors made an analysis of problems of strategy of surgical treatment of 132
patients with aortal stenosis complicated by calcinosis. Detailed indications to
surgical treatment for stenosis of the aortal valve are given depending on the
stage of the disease and complications. The nuances of the technique of
performing the operation of prosthesis of the aortic valve are described.
PMID- 11011396
TI - [Age-dependent dynamics of biomechanical and hydrodynamic properties of the valve
aortic complex of man].
AB - A comparative analysis of geometrical, biomechanical and hydrodynamic
characteristics of the valve-aortic complexes taken from humans of different age
has shown a determining role of distensibility of the aortic root in the
functioning of valve cusps. An alteration of geometrical relationships of
elements of the aortic root, its less distensibility, worse biomechanical and
hydrodynamic characteristics of the aortic valve in humans older than 50-60 years
of age is established.
PMID- 11011398
TI - [A comparative evaluation of different methods of esophagoplasty].
AB - Intraoperative comparative oxyhemo- and thermometry of fragments of the
gastrointestinal tract used for creation of the artificial esophagus were
performed in 41 patients. The relationship of the degree of ischemic alterations
in the transplant tissues and the development of postoperative complications was
determined.
PMID- 11011399
TI - [Long-term outcome of surgical treatment of patients with esophageal cancer].
AB - Under study were the results of surgical treatment of 185 patients with
esophageal carcinoma. One-year survival was 75.4%, 2-year survival was 49.6%, 3
year--43.4%, and 4-year survival--33.3%. Among the patients with tumors with the
invasion degree T1, T2, T3 and having no metastases to the regional lymph nodes
the resection of the esophagus in combination with the extended lympho dissection
resulted in 4-year survival in more than 50% of the patients operated upon. In
patients with tumors T3N1, T4N1 and especially with the simultaneous involvement
of several lymph collectors the 4-year survival was 21.4%. The operative
intervention at this stage of the disease should be considered as a palliative
means in the greater part of the patients.
PMID- 11011400
TI - [Surgical treatment in cancer of the right half of the colon complicated by
occlusive ileus].
AB - Results of treatment of 68 patients with carcinoma of the right half of the colon
complicated by occlusive ileus are presented. The operation of choice is thought
to be radical surgical intervention with the primary ablation of the tumor.
Palliative operations were performed on 28 (41.2%) of 68 patients with occlusive
ileus of the right half of the colon having risk factors, radical operations--on
40 patients (58.8%). Seven patients died at the postoperative period. Over-all
lethality was 10.3%.
PMID- 11011401
TI - [Mechanism of action of paravasal infiltration].
AB - In order to study the mechanisms of action of paravasal infiltration the content
of middle mass molecules and general thiol groups in the central and regional
blood flow were studied in 65 patients with obliterating atherosclerosis. The
relationship between the stage of extremity ischemia and concentration of general
thiol groups was shown.
PMID- 11011402
TI - [Assessment of the value of certain clinical and laboratory indices in
improvement of the diagnosis of acute appendicitis in children].
AB - The results of diagnosis and treatment of 1483 children were analyzed in order to
determine the frequency of clinical symptoms and laboratory indices in children
with acute appendicitis. Seven most valuable objective parameters were stressed
which allowed to differentiate the strategy in situations difficult for
diagnosis.
PMID- 11011403
TI - [Surgical treatment of children with autosomal dominant polycystic kidney
disease].
AB - The authors dealt with 59 children with different variants of polycystic kidney
disease. The age of the patients was from 1 month to 19 years. The autosomal
dominant type of inheritance was noted in 52 patients, in 24 of them percutaneous
ignipuncture, lumbotomy with ignipuncture and dissection of the cysts,
endovideosurgical opening and dissection of the cysts transperitoneally and
retroperitoneally were performed. Long-term results were followed during the
periods from 6 months till 17 years. Good results were obtained in 12 patients,
satisfactory--in 2 patients, unsatisfactory--in 7. The most effective methods are
traditional lumbotomy and endovideosurgical correction which are not followed by
growth of cysts in the operated kidneys at the postoperative period.
PMID- 11011404
TI - [Infectious complications in electric cardiac stimulation].
AB - There were 4424 patients operated for alterations of the cardiac rhythm. Primary
electrocardiostimulation was performed in 3183 of them, reoperations in 1241
patients (39%). Infectious complications took place in 146 patients (3.3%). Based
on their experiences the authors developed the strategy of treatment of patients
with purulent complications and sepsis depending on their character and time of
their appearance.
PMID- 11011405
TI - [New trends in the treatment of liver abscesses].
AB - The authors share their experiences with treatment of 85 patients with abscesses
of the liver aged from 17 to 83 years. The size of abscesses was from 2.5 to 23
cm in diameter. For the topical diagnostics the following methods were used:
ultrasound scanning, computed tomography, scintigraphy, diagnostic puncture
biopsy of the liver, laparoscopy etc. Decision between the methods of operative
treatment depended on the concrete clinical situation. Both open and minimally
invasive methods were used. Hydropressive technologies and ozone therapy were
used for better sanitation of the abscess cavity. A new method of the assisted
minimally invasive intervention was developed especially for treatment of
patients with large abscesses of the liver. The new technologies allowed to
reduce the amount of postoperative complications and to make the time of staying
at the hospital substantially shorter.
PMID- 11011406
TI - [Hemorheological indices in patients with amebic abscesses of the liver and their
correction].
AB - Hemorheological indices were studied in 89 patients. In 61 patients the authors
have revealed somewhat increased viscosity potential of blood and negligible
changes in the aggregation activity of erythrocytes which is thought by the
authors to be due to the saved compensatory potentialities of the organism. In 28
patients with the complicated course of the disease the rheological parameters of
blood became worse because of the suppressed compensatory potentialities of
organism. So, in addition to the adequate transfusion-infusion therapy the
complex of treatment must include immunostimulating means (Levamisole,
Prodigiozan, Tactivin etc.).
PMID- 11011407
TI - [Antioxidant therapy with xymedon of patients with chronic osteomyelitis].
AB - An investigation of the antioxidant activity of blood plasma allowed a conclusion
to be made of an alteration of the free radical processes in patients with
chronic osteomyelitis. Experimental data on the influence of the antioxidants
Xymedon and Methyluracil on the main free radicals, lipid peroxidation and
chemiluminescence of peritoneal macrophages of rats allowed the substantiation of
using the medicines in the complex treatment of patients in the pre- and
postoperative periods. As a result, in 25 patients Xymedon improved the blood
indices, increased antioxidant activity of plasma and reduced the amount of
recurrences of the disease as compared with the patients taking Methyluracil.
PMID- 11011408
TI - [Complex treatment of patients with complicated forms of erysipelas].
AB - The authors made an analysis of variants of treatment strategy and its results in
patients with different forms of erysipelas. The use of complex conservative and
operative treatment allowed lethality to be reduced from 4 to 1.9%, in patients
with severe course of the disease the frequency of complications being reduced to
10%.
PMID- 11011409
TI - [Extracorporeal hemocorrection in acute pancreatitis].
AB - An experience with using 340 operations of extracorporeal hemocorrection in
complex intensive therapy of 160 patients with acute pancreatitis has been
generalized. In 111 of these patients (69%) pancreatic necrosis complicated by
the syndrome of multiple organ failure was diagnosed. Based on the mechanisms of
medical efficiency the authors have developed differential indications for using
different extracorporeal technologies depending on the clinico-laboratory profile
of the endogenous intoxication, structure and degree of organic and systemic
dysfunctions. The adoption of such technologies allowed lethality to be reduced
from 37.5 to 27.6%.
PMID- 11011410
TI - [Determination of indications for preoperative blood transfusion in patients with
chronic ulcer of the stomach and duodenum complicated by hemorrhage].
AB - Results of the examination and treatment of 61 patients with chronic
gastroduodenal ulcers complicated by bleeding have been analyzed. The possibility
is shown to use hemoglobin indices for the estimation of severity of bleedings
and for determination of indications for preoperative hemotransfusion to patients
with chronic gastroduodenal ulcers complicated by bleeding. It was found that to
refuse or reduce blood transfusion at the preoperative period was possible
depending on the initial level of hemoglobin with the purpose of blood saving and
in order to decrease the risk of reactions to hemotransfusion and complications.
PMID- 11011412
TI - [Video endoscopy of the residual cavity in hydatidectomy of the liver].
AB - Results of treatment of 162 patients with echinococcosis of the liver were
analyzed. Traditional surgical treatment of these patients was followed by
endovideoscopy of the residual cavity of the liver. During endovideoscopy of the
residual cavities the remnants of the chitinous membranes and small daughter
vesicles not noticed during the open stage of the operation were removed in 7.4%
of the patients, in 25.9% of the patients cystobiliary fistulas were detected.
The endovideoscopy considerably improves revision of the residual cavities of the
liver and facilitates liquidation of cystobiliary fistulas which gives better
results of the treatment of such patients.
PMID- 11011411
TI - [Dynamics of fluid volumes of body sectors in patients after laparoscopic
surgery].
AB - An investigation of the state of volumes of the organism's fluid sectors
(general, extra- and intracellular fluid) by a noninvasive method of double
frequency impedancemetry has revealed the influence of preoperative preparing the
patients and restriction of the water regimen after operation upon the
development of moderate dehydration of the extracellular sector. During the
operation lasting about an hour the intravenous administration of 400 ml of
crystalloid solutions maintains the volumes of fluid sectors within the due
values. These solutions injected in greater volumes result in accumulation of the
extra- and intracellular fluid. The antiperistaltic purgation of the intestine
before the operation reduces the concentration of calcium in blood by 1 mmol/l at
an average.
PMID- 11011413
TI - [Nephrectomy in general surgical hospital].
AB - In the central regional hospital 50 nephrectomies were performed for traumas and
different diseases of the kidney, 44 of them being fulfilled through a
laparoscopic access. This access allowed the volume of operation to be expanded
in 58% of the patients. In 8% of the patients massive hemorrhage took place. Four
patients died. Nephrectomy following pretreatment of the renal vessels allows to
reduce risk of the operation.
PMID- 11011414
TI - [Surgical treatment of middle-aged and elderly patients with chronic ischemia and
distal occlusions].
AB - Operative treatment for critical ischemia was performed on 346 elderly and senile
patients. An assessment of the distal bed and outflow pathways has shown the
conditions for the reconstruction of the vessels to be unfavorable in 257 (74%)
patients. Femoro-proximal-popliteal shunts were made in 82 patients with good
effect in 74 of them. Femoro-distal-popliteal and tibial shunts were made in 62
patients with good effect in 52. In 12 patients out of 20 with the isolated
plasty of the profound femoral artery better blood flow and arrest of pains in
rest were noted. Lumbar sympathectomy was performed in 142 (41%) patients, in 46
of them it was combined with continuous intraarterial infusion and in 20 patients
-in combination with the rotor osteotrepanation on the femur and shin. Good
results after sympathectomy were noted in 102 patients.
PMID- 11011415
TI - [Infectious lesions of recurrent laryngeal and hypoglossal nerves as a rare
complication of phlegmon of deep neck spaces].
PMID- 11011416
TI - [Late rupture of the left ventricular posterior wall with the formation of
pseudoaneurysm after implantation of mitral and aortic valve prostheses].
PMID- 11011418
TI - [Treatment of a patient with a large defect of the vertical part of the duodenum
and fistula formation].
PMID- 11011417
TI - [Perforating gunshot wound of the duodenum with injury of the inferior vena cava
and multiple wounds of the jejunum].
PMID- 11011419
TI - [Hemicolectomy in a patient with hemophilia A].
PMID- 11011421
TI - [Certain general problems of surgery].
PMID- 11011420
TI - [Diagnostic tactics in localized fibroadenomatosis of the breast].
AB - Results of the examination and treatment of 203 patients with localized
fibroadenomatosis of the mammary gland are described. The authors give an
estimation of diagnostic algorithms used when detecting the physical signs of the
disease. It was shown that the examination of patients with the palpation signs
of nodular mastopathy should necessarily include mammography which can eliminate
unwarranted risk of hypodiagnosing carcinoma of the mammary gland and determine
the group of patients in whom the emergency operation is not necessary.
PMID- 11011422
TI - [The 7th International Conference of Surgeons-Hepatologists of Russia and CIS
countries (City of Smolensk, 14-16 November 1999)].
PMID- 11011423
TI - [Risk factors in the etiology of lung cancer].
PMID- 11011424
TI - [Injuries of extremity blood vessels].
PMID- 11011425
TI - [Incidence of high grade prostatic intraepithelial neoplasia in urologic
practice].
AB - High grade (PIN AG) intraepithelial neoplasia of the prostate is a likely
precursor of prostate adenocarcinoma (PA) because of their association. Since the
risk to suffer PA increases in patients with no previous PIN AG, its finding
requires an arduous search for PA. This paper reviews the incidence of PIN AG in
499 histological studies in prostate transrectal biopsies, prostate TUR and
adenomectomy specimens and radical prostatectomy (RP) sections. Evaluation of
data obtained, type of presentation and association to prostate carcinoma,
indicating the approach taken in the various cases.
PMID- 11011426
TI - [Prostatic carcinoma. Radical prostatectomy. Impact of neoadjuvant hormonal
treatment].
AB - OBJECTIVE: To assess the influence of neo-adjuvant hormone therapy on the
pathologic stage, margins and disease-free survival in patients with T1-T2
prostate cancer after radical prostatectomy. MATERIAL AND METHODS: Forty-two non
randomised, T1-T2 patients who underwent complete neo-adjuvant blockade and
radical prostatectomy between 1988-1998 were included in the study. This group is
part of a larger cohort of 220 T1-T2 patients treated with radical surgery. The
group is compared to: a) the remaining patients (178) (Group I) and b) a selected
group (54 patients) of consistent characteristics relative to clinical variables
(Group II). Mean follow-up: 35 months; median: 32 months. RESULTS: Compared to
Group I patients with neo-adjuvant therapy show worse Gleason (p: 0.01), worse
clinical stage (p: 0.02), higher rate of patients with high clinical risk (p:
0.03), and higher PSA (though not statistically different). No differences were
seen relative to pathological status or margins. Compared to Group II (54
patients) no differences are found in clinical or pathological variables. Groups
are comparable in terms of progression-free survival. CONCLUSIONS: Neo-adjuvant
hormone therapy in high clinical risk, T1-T2 patients does not involve
improvement in pathological stage, margins or progression-free survival.
PMID- 11011427
TI - [Ureteroscopy as diagnostic and treatment method in ureteral processes: our
experience].
AB - Endoscopic approach to the ureter both as a diagnostic procedure in various
diseases and treatment of low ureteral lithiasis is a widely used technique.
Review of case reports where this technique was used over the last four years. A
total of 73 ureteroscopies were conducted, 64 as therapeutic approach (89.04%)
and 9 for diagnosis (10.96%) achieving an overall 94.4% success rate. Multiple
variables such as type and location of the stones, patient's age and sex,
diagnostic methods, length of stay etc. All the above data were used for a
descriptive analysis of the situation in our centre. In our experience,
ureteroscopy is a good therapeutic option for low ureteral lithiasis, mainly when
no extracorporeal lithotrity is available, and an excellent diagnostic tool in
other ureteral processes when more traditional methods fail.
PMID- 11011428
TI - [Morphologic course of prostatic hyperplasia].
AB - OBJECTIVE: To find a morphologic model of the development of prostate
hyperplasia. METHODS: Study of the transitional zone in 60 patients (30 with
infravesical obstruction, 30 with no obstructive symptoms) and quantification of
the involved surface, number of pure stromal and glandular-stromal nodes, node
area for each of them, and non-nodular area of the transitional zone, correlating
each parameter to age based on clinical status. RESULTS: The greater transitional
zone area is seen in patients with obstruction: 1376.83 +/- 408.17 mm2 vs 321.39
+/- 151.49 mm2 in asymptomatic patients, mainly due to a higher number of
glandular-stromal nodes (17 vs 2.2) and their size, with a correlation to age (p
= 0.03). Moderate increases of non-nodular areas are also found. CONCLUSIONS:
These findings suggest that onset of prostate hyperplasia may be due to a
consistent increase of the transitional area, and that in some patients, probably
because of local factors, nodular development occurs as a result of both an
increase in nodes number and size.
PMID- 11011429
TI - [Radical prostatectomy in stage pT3C stage prostatic adenocarcinoma].
AB - OBJECTIVES: To assess the efficacy of surgery in pT3c patients; to discern
whether this is an independent influential factor for survival and clinical
factor for diagnostic prediction. MATERIAL AND METHODS: Forty-five pT3c (TNM
1982) patients from a cohort of 220 subjects with T1-T2 prostate cancer who
underwent radical prostatectomy. Mean and median follow-up: 42 and 36 months,
respectively. RESULTS: pT3 stage accounts for 20% (45/220) patients. They display
a significantly higher mean PSA (25 +/- 2 ng/ml) (0.001), worse Gleason (0.0002)
and clinical stage (0.0003), greater margins involvement (0.0007), and
biochemical (0.02), local (0.05) and metastatic (0.001) progression. Independent
influential factors are: PSA > 20 ng/ml; T2bc and Gleason 7-10. From these values
patients can be divided into 3 risk groups: a) Group I (0-1 unfavourable
variables): risk of seminal vesicle involvement 7%; Group II (2 unfavourable
variables): risk 47%; Group III (3 unfavourable variables): risk 61%. Progression
free survival: significantly lower than patients with pT2 (58 +/- 8% vs 66 +/- 6%
at 5 years) (0.002), but similar to those with pT3ab (0.91). Seminal vesicle
involvement is not an independent influential factor (Cox's multivariate study).
Influential factors are PSA, Gleason and clinical stage. CONCLUSIONS: pT3c
tumours are not an independently influential group in progression-free survival.
Progression-free survival is lower than pT2 but similar to pT3ab. Their poor
prognosis is dependent on association to negatively influential clinico
pathological factors.
PMID- 11011430
TI - [Survival in prostatic cancer, treated conservatively].
AB - OBJECTIVES: To analyse the survival rate among prostate cancer patients with
conservative treatment. To compare survival between individuals with localised
and invasive tumours, as well as between subjects below and above 70 years old at
the time of diagnosis. METHODS: This study includes 80 patients diagnosed with
prostate cancer between 1987 and 1988 at the Urology Service of the Central
Hospital of Asturias (Spain). The cases were taken and followed retrospectively
for 10 years. Kaplan Meter curves and Cox regression analyses were used for
studying patients globally. Patients were categorised by tumour stage as well as
by their age at the time of initial diagnosis. RESULTS: 10 patients remained
living 5 years after diagnosis, corresponding to a 17% survival rate. However, 10
years after diagnosis, only 1 subject remained alive. Mean survival expressed in
days was 677.28% of the cases died after the first year of diagnosis. Significant
differences in survival rates were not found with regard to the age of patients
ar the time of the diagnosis. However, survival is significantly higher among
patients with localised tumours as opposed to invasive ones (p = 0.025; RR =
2.3). CONCLUSIONS: The survival rates is low in this study. The majority of
tumours were at advanced stages when diagnosed and were mostly found in very old
patients. Today, the use of PSA allows doctors to diagnose prostate cancer at
earlier stages and in younger patients. This has lead to an increase in the
frequency of radical prostatectomy. Future research should investigate whether
this increase in radical prostatectomy has significantly changed the mortality
rate of patients with prostate cancer.
PMID- 11011431
TI - [Transrectal ultrasonography in the assessment of patients after radical
prostatectomy. Normal and pathologic ultrasonography anatomy of vesico-urethral
anastomosis].
AB - OBJECTIVE: To determine the ultrasound characteristics of the vesico-urethral
anastomotic complex in patients with radical prostatectomy to separate normal
prostate fossae from those affected by local recurrence or residual tumour.
MATERIAL AND METHODS: Between January 1998 and June 1999 15 ultrasound guided
transrectal biopsies of vesico-urethral anastomosis or prostate fossae were
performed in patients with radical prostatectomy. The selection criteria to
perform puncture in these patients were a negative extension study (abdominal
pelvic CT and bone scan), PSA higher than 0.4 ng/mL and/or suspicious DRE. The
study was completed with 10 transrectal ultrasound (TRU) after radical
prostatectomy in patients with normal PSA and DRE. TRU parameters in patients
with tumour-positive biopsies were compare to those from patients with negative
biopsies and those obtained from TRU in patients with both normal PSA and normal
DRE. RESULTS: The ultrasound parameters that best described prostate fossa
abnormalities were the presence of hypoechoic masses or nodes and the integrity
or not of the retro-anastomotic fat layer. When a hypoechoic mass or node was
found at the anastomosis level, 80% biopsies were positive for tumour local
recurrence. The percentage increases when changes are seen at the retro
anastomotic fat layer. CONCLUSIONS: In spite of a good correlation between
ultrasound abnormalities and positive biopsies, ultrasound findings from the
vesico-urethral anastomosis in patients with radical prostatectomy are not well
defined. Nodes or ultrasound irregularities can exist in normal prostate fossae
as well as normal anastomosis ultrasound in the presence of tumoral relapses. We
believe TRU of vesico-urethral anastomosis to be the best method available to
evaluate local recurrence or tumoral persistence after radical prostatectomy.
PMID- 11011433
TI - [Testicular embryonal carcinoma with contralateral synchronous intratubular germ
cell neoplasia: analysis of a case].
AB - We report the case of a 20-year old male with a right testicular tumor. Bilateral
orchidectomy was practised considering the synchronous clinical,
ultrasonographical and histological (intraoperative biopsy) findings of the left
testis. The definitive pathological report showed a right embryonal carcinoma
with wide intratubular germ cell neoplasia (IGCN) of the contralateral testis.
IGCN (formerly carcinoma in situ) is present in about 5% of cases in the
contralateral gonad of those patients with a testicular neoplasm. More than 50%
will develop cancer in that testis. Clinical and physical examination findings
are usually unspecific. The diagnosis of IGCN is based on biopsy, although
ultrasonography could give some data too, as some authors report. We analyze the
therapy options for IGCN: (orchidectomy, chemotherapy, radiotherapy, or "wait and
see"). In our case, the first one was made. Chemotherapy was used due to
existence of retroperitoneal lymph node metastases, with an excellent follow-up
afterwards.
PMID- 11011432
TI - [Primary malignant melanoma of the female urethra. Report of a case].
AB - Primary malignant melanoma of the female urethra is a rare tumour with great
agressivity and poor prognosis. An early diagnosis may benefit of radical surgery
and adjuvant immunotherapy with curative effect. We present a sixty-five years
old female with a malignant melanoma of urethra and a secondary additional
melanoma in vulva, that was treated with both radical ureterectomy and
vulvectomy. A bilateral inguinal lymphadenectomy and immunotherapy with alpha
interferon were added. The patient is free of disease one year postoperatively.
PMID- 11011435
TI - [Bladder compression by collateral veins].
AB - Many space-filling injuries (e.g. haematoma, abscess, aneurysm, lymphocele,
neoplasia etc.) may result in extrinsic compression of the bladder. We contribute
one case report of compression of the bladder from collateral venous circulation
in a patient who came for a left varicocele.
PMID- 11011436
TI - [Intraperitoneal bladder perforation in emphysematous cystitis].
AB - Contribution of one case report of a 69-year old diabetic male patient with
neurogenic bladder. The patient developed emphysematous cystitis and peritonitis
secondary to intraperitoneal perforation of the bladder. Emphysematous cystitis
is an uncommon clinico-radiologic entity more frequent in diabetic and female
patients and the elderly. Early diagnosis and treatment may avoid a fatal
outcome. The paper includes a review of this condition.
PMID- 11011434
TI - [Cystic ureteritis: importance of chronic infection-inflammation as etiologic
factor. Report of a clinical case].
AB - Cystic Ureteritis is a very rare disease. It is more commun in elderly patients.
This pathology is characterized by the formation of several submucous cystic in
ureter, pelvis and/or bladder. We project the importance of the infectious and
inflammatory factors as the disease etiology. We report a case of a woman with
recurrent urinary tract infection, coral lithiasis and left ureteritis cystica.
It is included a literature review and we explain the main clinical, diagnostic
and therapeutic aspects.
PMID- 11011437
TI - [Wolfram syndrome. Urologic implications].
AB - OBJECTIVES: We report on four new cases of Wolfram's Syndrome. We emphasize in
urological aspects of this disease. PATIENTS AND METHODS: Three male siblings.
The other patient is also a male, without familiar relation with the other ones.
All four patients presents different levels of urological alterations, mainly
urinary collecting system dilation and decrease in detrusor muscle contractility.
CONCLUSIONS: Urological findings are cardinal aspects in Wolfram syndrome. Due to
its high frequency and prognostic value in natural history of disease. Urological
disease seems to be within a systemic neurological tissues affectation of
etiology that remains unknown.
PMID- 11011439
TI - [Gonadal thermoregulation in aquatic mammals. An evolutionary guarantee for the
preservation of the species].
PMID- 11011438
TI - [Giant inguinoscrotal bladder hernia].
AB - Inguinoscrotal bladder hernia occur in 0.4 to 3% of general poblation, though
massive hernia are much rare. We present a new case of a giant inguinoscrotal
bladder hernia, which was solved by surgery. It includes a clinical, diagnostic
and therapeutic aspects, and a review of the relative literature.
PMID- 11011440
TI - [Effect of sacral roots block in the prostatic structure of the rat].
AB - OBJECTIVE: To validate a simplified model of neural manipulation of the lower
urinary tract of the rat, by means of alcoholic blockade of sacral roots.
MATERIAL AND METHODS: Twenty Sprague-Dawle rats (aged 3 months) underwent alcohol
sacral root blockade under total anesthesia with previous needle placement
monitoring (electrostimulation). After 28-30 days, ipsilateral ventral prostatic
lobe (VL) was obtained. Macroscopic and light microscopy (LM) studies were
performed (computerized image analysis). Results were compared with 20 LV from
non manipulated rats. RESULTS: A slight non significant decrease of LV weight in
the blockade group was notice. LM study showed a reduced epithelial height after
manipulation. Gland compartment mean proportions were: control group: 28.1%
(epithelial), 29.8% (stromal), y 70.2% (glandular -lumen plus epithelium-); study
group: 30.5% (not significant), 37.4% y 62.3% (both p < 0.05) respectively.
Epithelium area did not suffer any variation. A reduced vascular overall count
was noted in the study group. Ipsilateral diffusion of blockade solution was
shown in 9 rats (45%), and bilateral in 11 (55%). CONCLUSIONS: Alcoholic sacral
root blockade produces an atrophy of the glandular component (due to luminal
shrinkage, without epithelial change). No differences were found after the
macroscopic study. This study could not reproduce the changes produced after
standard surgical denervation, therefore we cannot recommend this method to be
used in future models.
PMID- 11011442
TI - [Relationship between tumor recurrence and the expression of the p53 gene in
primary superficial transitional carcinoma of the bladder].
AB - Contribution of 60 patients with primary surface transitional cell tumours of the
bladder where nuclear expression of p53 protein was prospectively studied and
compared to known prognostic factors in an attempt to find out its role in the
development of relapses. An statistically significant relationship was found
between the protein expression and cytology, tumoral multifocality, stage,
relapse development and tumoral progression. It can be concluded that expression
of this protein can be of use as relapse predictor.
PMID- 11011441
TI - [Initial superficial bladder tumors: our experience. Our criteria. Study Group of
Bladder Tumors].
AB - OBJECTIVES: Evaluation of a homogeneous series of Superficial Primary TCC of the
Bladder. Utility of randomized biopsies (BMN). Study of risk factors and risk
groups as a basis for determining treatment and followup patterns. MATERIALS AND
METHODS: Survey of 1,529 PSBT cases that underwent TURB and BMN, with a mean
followup of 4.2 years. Strict statistical treatment: multivariate analysis using
Cox logistic regression according to Kaplan-Meier curves. RESULTS: Tumor features
of note: single tumor (65%), smaller than 1.5 cm (45%), high grade (G3: 26%), and
high stage (T1: 64%). BMN showed associated CIS in 284 cases (19%). Main risk
factors for recurrence were multiplicity, size > 3 cm and association with CIS.
The main risk factor for progression was grade 3 (OR 19.9). Grade 3 and
association with CIS were found to increase mortality risk. On the basis of this
data, we grouped tumors according to low-, middle-, and high-risk, and
established our proposed treatment and followup for each group. CONCLUSIONS: This
multivariate analysis of a homogeneous cohort of 1,529 primary superficial
bladder tumor cases allowed vs to determine risk groups for treatment and
followup.
PMID- 11011443
TI - [Neoadjuvant chemotherapy MVAC in the treatment of infiltrating bladder
carcinoma].
AB - INTRODUCTION: Aiming to preserve the bladder in patients with infiltrative
carcinoma of the bladder and to offer patients improved quality of life with no
detriment for survival, a therapeutical protocol was set up. MATERIAL AND
METHODS: Between August 1988 and January 1997 63 patients with stage T2 and T3a
infiltrative carcinoma of the bladder, with no metastasis or node extension
detectable with imaging techniques were treated in our unit. 45 of these patients
met all protocol criteria and were given 3 neoadjuvant chemotherapy courses with
MVAC (methotrexate, vincristine, adriamycin, cisplatin). INCLUSION CRITERIA: age
under 75 years, Karnofsky greater than 50%, leucocytes greater than 2,500 cell/mL
and platelet greater than 100,000/mL. Following chemotherapy, re-assessment was
performed through lab tests, chest X-rays, abdomino-pelvic CT, bone scanning,
cystoscopy, multiple randomized biopsies, tumoral bed scar resection and
resection of relapsed urothelioma. Patients with complete remission were given
radiotherapy. Those showing stabilisation of progression were proposed to undergo
cystectomy. Fisher's test or chi 2 test were used for the comparison of
qualitative variables. The survival analysis was performed using the Kaplan-Meier
method. The curves comparison was done with Breslow's exact test. A Cox's
proportional risk method allowed to calculate the relative risks together with
their 95% confidence interval. RESULTS: 53.7% patients included in this protocol
showed complete remission, 41.5% stable disease and 4.9% progression. 62.2% of
patients were given radiotherapy versus 17.8% who underwent cystectomy. 20%
received other therapies after rejecting both cystectomy or radiotherapy. Median
follow-up was 43.38 months. Overall median survival was 96 months. The accumulate
probability of survival at 4 years was 79%. 50% patients with complete clinical
response relapsed during follow-up. Tumoral stage of those who relapsed was lower
than the initial one in 63.7% cases, remained the same in 18.2%, and higher in
18.2%. With regards to grading, 66.7% patients had lower grading at relapse if
tumour was initially grade 2. For those with initial tumour grade 3, only 20% had
a lower grade. CONCLUSION: 64.4% patients retained their bladder. In 26.7% there
was demonstrable metastatic disease. No differences were seen in the distribution
or survival time based on the different treatment given after chemotherapy (p =
0.22). Patients with complete remission after chemotherapy have greater actuarial
survival which is statistically significant (p = 0.04).
PMID- 11011444
TI - [N1 prostatic adenocarcinoma treated with radical surgery and immediate hormonal
management].
AB - OBJECTIVES: To study the survival in patients with prostate adenocarcinoma, lymph
nodes involvement in the intraoperative pathological examination, evaluating both
radical surgery and early ablation as treatment. Identification of clinical
factors that can predict node involvement. METHOD: 20 patients who underwent
radical prostatectomy between 1988-1998 were included in the study. All patients
clinically diagnosed with T1-2N0Mx prostate adenocarcinoma (T.N.M. 1992), single
metastatic node involvement in the pathological study and early sub-albuginea
orchidectomy. This group was compared to a 200-patient control group also with T1
2N0Mx prostate adenocarcinoma but with no pathologic nodular involvement.
Statistical study: contingency 2Xb tables (Pearson's chi 2 or Fisher's exact
test) to compare qualitative variables; Student's t test for means comparison;
Kaplan-Meier for actuarial survival calculations and comparison of Log-rank
survival curves. For the study of clinical variants with influence in node
involvement a logistic regression model was used. RESULTS: Mean age was 63 +/-
0.8 years. Median follow up 56 months. Mean PSA 33 +/- 4.4 ng/mL and 55% had
Gleason 5-7. 16 patients were stage pT3. Specific 5-year survival was 90 +/- 8%
and biochemical progression free survival 63 +/- 12%. Clinical variables with
statistical significance for node involvement are: pre-surgical PSA greater than
20 ng/mL (RR = 4.6), and Gleason higher than 4 (RR = 3). The remaining variables
showed no statistical significance. CONCLUSIONS: Gleason and PSA are the only
clinical values that predict node involvement. The procedure performed obtains
good results and a survival comparable to that of the control group.
PMID- 11011447
TI - [Percutaneous nephrostomy as management technique of obstructive uropathy: review
of 105 cases].
AB - 105 percutaneous nephrostomies in 73 patients. Indication for nephrostomy was
obstruction in the drainage system in all cases. Nephrostomy was bilateral in 24
cases. Reasons for nephrostomy were: lithiasis in 35 cases, carcinoma of the
bladder in 17, post-surgical iatrogenic stenosis in 13, prostate carcinoma in 9,
cancer of the rectum in 9, infection in 5, neoplasia of the upper urinary tract
in 5, retroperitoneal fibrosis in 3, glandular cystitis cystica in 3, ovarian
cancer in 3, congenital in 2, lymphoma in 1. Six case were single-kidney
patients. Renal puncture through the lower calyceal group was the preferred
approach. Purulent urine was extracted in 10 cases. Complications of nephrostomy
included haematuria in 34 cases, contrast extravasation in 8, fever in 6, 1 case
of death due to septic shock, 2 perirenal haematoma (nephrectomy was required in
1 case), and catheter detachment in 5 cases. All patients showed improvement of
both clinical signs and symptoms, and lab results.
PMID- 11011445
TI - [Diagnostic algorithm based on a multivariate model to reduce the percentage of
negative prostatic biopsies in patients with changed PSA or suspicious rectal
palpation].
AB - OBJECTIVES: To determine what tests have a better diagnosis utility in patient
with suspected prostate cancer due to PSA equal or greater than 4 ng/ml or
abnormal digital rectal examination in order to reduce the number of negative
prostate biopsies. MATERIAL AND METHODS: We carried out a ultrasound-guided
sextant transrectal biopsy in a series of 400 patient with prostate-specific
antigen (PSA) levels equal or greater than 4 ng/ml or abnormal digital rectal
examination. All patients had also transrectal rectal ultrasonography to value
the echographic prostatic characteristics and the prostatic volume, and a free
PSA determination. RESULTS: The free/total PSA ratio (PSAl) and the PSA density
(DPSA) were the most powerful predictors of prostate cancer, both with a 66%
sensitivity and a 70% specificity (at a 0.15 cutoff), followed by the total PSA
(PSAt), the digital rectal examination and the hypoechogenic prostatic nodules.
We constructed a logistic multivariate model with these data. The outcome
variable of logistic model was the probability of having prostate cancer. The
significant predictive variables of the model were the PSAl, the DPSA, the
digital rectal examination and the presence and extension of hypoechogenic
prostatic. This model had a 81% sensitivity and 79% specificity at a 0.24
probability cutoff. We considered a 0.1 probability cutoff to reduce the number
of false negative. With this strategy the sensitivity was 94% and the specificity
54%. If we had applied this model to the patient of our series then, we would be
able to avoid prostate biopsy in 164 cases (the 41% of the patient), leaving only
7 cases without diagnosis of prostate cancer. CONCLUSIONS: The most effective
combination parameters were the digital rectal examination, PSAl, presence and
extension of prostatic hypoechogenic zones and DPSA. This combination allows us
to diminish the percentage of negative prostate biopsy in patient with prostate
specific antigen (PSA) levels equal or greater than 4 ng/ml or abnormal digital
rectal examination without significantly descending the number of detected
prostate cancers.
PMID- 11011446
TI - [Prostatic rebiopsy. Prognosis factors of the anatomopathologic result].
AB - The indications for repeat prostate needle biopsy after a previous biopsy are not
defined. We examined 107 prostate biopsies (in 98 patients) without a diagnosis
of malignancy, which we repeat. Carcinoma was detected in 31 patients (31.6%). We
didn't find statistic relationship between the repeat biopsy's outcome and:
interval between biopsy and repeat biopsy, PSA value, PSA density (biopsy), PSAD
of the transitional area (PSAD ad., on repeat biopsy). We found relationship
with: prostatic weight (p = 0.002 on the biopsy, p = 0.0002 on the repeat
biopsy), volume of the transitional area (p = 0.02 on the biopsy, p = 0.0001 on
the repeat biopsy), PSA value (p = 0.02, on the repeat biopsy), PSAD ad. (p =
0.002, on the repeat biopsy), and with PSA velocity (p = 0.008). We only found
clinic usefulness for the PSA velocity: patients with PSA velocity greater than 1
ng/ml/year are at high risk for prostate carcinoma on the repeat biopsy,
specially in small prostates.
PMID- 11011448
TI - [Primary bladder actinomycosis].
AB - Primary actinomycosis of the bladder is an infrequent presentation of this
condition. The main concern is obtaining a differential diagnosis from tumours of
the bladder and the subsequent impact this has on the therapeutic choices.
Contribution of one case report of a male patient with actinomycosis of the
bladder, with remarks on relevant diagnostic (including differential diagnosis)
and therapeutic data.
PMID- 11011450
TI - [Malignant fibrohistiocytoma of the bladder].
AB - We report on new case of a rare vesical tumour. We result the importance of
immunohistochemistry and ultrastructural study to support the diagnosis of
malignant fibrous histiocytoma of the urinary bladder. There has been described
another 16 cases of this tumour in the literature, however, only four of them
five with ours- reports an extensive immunohistochemical and ultrastructural
study. The rarity of vesical localization of this tumour may delay its diagnosis.
It must be supported by a immunohistochemistry and/or ultrastructural study, in
order to differentiate from other tumours with fibrohistiocytoma-like pattern:
leiomyosarcoma and sarcomatoid carcinoma of the bladder. After radical removal of
tumour, adjuvant therapy is recommended both systemic chemotherapy and local
radiotherapy, although survival rates are over 5.3 months after first
therapeutical actuation.
PMID- 11011449
TI - [Renal malacoplakia. Report of a new case].
AB - The malacoplakia is an infrequent granulomatous inflammatory disease which
pathogenesis is not well understood and affects predominantly the genitourinary
system, through every organ can be affected. We present a case of unilateral
renal malacoplakia in a male that made ist debut with septic shock and
perinephritic abscess. It was operated under the suspicious diagnostic of renal
neoplasm. The histologic study grave us the diagnosis of renal malacoplakia
extending until the skin. After nephrectomy and medical treatment the patient had
an uneventful course.
PMID- 11011451
TI - [Technical solution in kidney retransplantation in a patient with femoro-femoral
bypass].
AB - Over the last decade kidney transplantation has become a common therapeutic
procedure for patients with end-stage renal diseases. Between 1988 and 1998
donors rate per million population has dramatically increased in our environment,
thus providing us with more chances to offer kidney transplantation to a larger
number of patients. The technico-surgical difficulties that have to be faced
however, are increasingly frequent and require a search for new approaches and
innovative changes to the usual surgical techniques for our patient's benefit.
PMID- 11011452
TI - [Treatment of pyelocaliceal transitional cell carcinoma with partial
nephrectomy].
AB - Nephroureterectomy is the choice treatment for tumours of the upper urinary
tract. Conservative surgical management is sometimes warranted due to the risk of
renal failure or just as palliative treatment. Contribution of two cases of
transitional tumours in the pyelocalyceal zone treated with partial nephrectomy,
and discussion of the usefulness and indication of conservative surgery for these
tumours.
PMID- 11011453
TI - [Adrenal cortex carcinoma with right atrium involvement. Surgery with
cardiopulmonary bypass].
AB - INTRODUCTION: Primary adrenal carcinoma is a low incidence tumour. About 50% are
functional and the majority result in Cushing's syndrome, while detection of the
rest is commonly incidental. Surgical management is through radical surgery. CASE
REPORT: A 36-year old female who presented with a one-month old abdominal pain in
the hypochondrium and the right lumbar fossa. Physical examination found a
discretely painful mobile mass. Adrenal hormones values were normal. Ultrasound
and CT studies detected a 14-cm adrenal tumour with cava vein thrombosis up to
the right auricle. The surgical procedure included laparotomy, liver mobilisation
and cardiopulmonary by-pass. The thrombus was completely removed by auriculotomy.
Therapy with mitotane and 5-fluorouracil was then instituted. Thirteen months
after surgery the patient is asymptomatic and tumour free. REMARKS: Dissemination
of adrenal tumours to veins ranges between 6 to 30%. Clinical manifestation of
cava vein and auricle involvement is variable but it may develop with no symptoms
due to collateral circulation. Pre-operative diagnosis is critical to plan for
adequate surgical approach. Ultrasound and computerised tomography can adequately
diagnose the process, but nuclear magnetic resonance provides more information on
the thrombus extension and location. In the absence of node spread, local
extension, or invasion of the cava wall prognosis is similar to that of patients
with no vein involvement. The best therapeutic option is surgery with removal of
the lesion and cardiopulmonary by-pass. Survival at 5 years is 43%. Post
operative administration of chemotherapy with mitotane is a useful and
recommendable choice.
PMID- 11011454
TI - [Glandular cystic cystitis].
AB - Cystic-glandular cystitis is considered as part of the urothelial pre-neoplastic
proliferative abnormalities. This group includes atypical hyperplasia. Von
Brunn's nidus, and cystitis cystica. They are a consequence of the changes
experienced at the urothelium level in response to inflammation, irritation or
carcinogens. Diagnosis is mainly based in the pathoanatomical study of the biopsy
obtained following endoscopic resection. The signs and symptoms it presents are
varied and show a clear relationship to distribution and extension of cysts.
Treatment is based in the removal of irritative factors. Cystectomy with urinary
by-pass may be necessary if required by clinical evolution.
PMID- 11011456
TI - Immunisation in the age of the human genome.
PMID- 11011455
TI - [Relationship between preoperative urine cultures and prostatic gland cultures in
patients surgically treated for prostatic benign hyperplasia].
PMID- 11011457
TI - The investigation of a 'cluster' of hepatitis B in teenagers from an indigenous
community in North Queensland.
AB - BACKGROUND: In early 1999, five teenagers from the same Indigenous community were
notified as having hepatitis B. Hepatitis B vaccine should have been offered to
this cohort of teenagers in a 'catch-up' program during the late 1980s when they
were of pre-school age. OBJECTIVES: To determine the vaccination status of
residents of the community born between 1981 and 1985 (inclusive) and to
ascertain the prevalence of markers of hepatitis B infection and carriage in the
incompletely vaccinated teenagers in this cohort. METHODS: Community health
records were examined to identify all residents in the study cohort. Immunisation
records were obtained from local hospital records and from a statewide
computerised vaccination database. Serological tests for markers of hepatitis B
infection and carriage were performed on blood samples from the incompletely
vaccinated teenagers. RESULTS: Only 44% of 235 teenagers who had their
vaccination status assessed were fully vaccinated. One hundred and eleven (47%)
of the cohort had not received any hepatitis B vaccine. Over 90% of the
incompletely vaccinated had been infected with the hepatitis B virus and 26% of
these were hepatitis B carriers. CONCLUSIONS: Despite the availability of an
effective hepatitis B vaccine and the recommendation for a catch-up program, the
pre-school aged cohort of children at the community were not effectively targeted
for vaccination. Hepatitis B remains a consequential infection in Indigenous
communities in North Queensland. IMPLICATIONS: Initiatives to control hepatitis B
need to be enhanced within existing maternal and child health, sexual health,
alcohol and drug and chronic disease management programs.
PMID- 11011458
TI - Health promotion and older people: the role of the general practitioner in
Australia in promoting healthy ageing.
AB - OBJECTIVE: The Commonwealth Government's Enhanced Primary Care initiative
supports measures to enhance the role of general practitioners (GPs) in promoting
healthy ageing as part of a population health approach. This paper comments on
how the health assessments can be conducted to best effect, to strengthen the
role of GPs in primary care and to promote autonomy and independence in older
people. METHOD: The relevant literature was collated to produce a review of
public health and health promotion approaches and to ascertain the effectiveness
of health promotion interventions for older people. A broad definition of health
promotion including primary, secondary and tertiary prevention was adopted.
RESULTS: The evidence base suggests there is scope for greater targeting of
health promotion activities towards older people. The rationale for the
Australian GP to assume a major health promotion role with their older patients
is provided. Associated barriers and enablers are discussed. CONCLUSIONS:
Prevention of disability is a key public health issue. The new MBS items may
enable systematic evaluation of function and assist healthy ageing for all older
people, including the frail aged. An increase in the preventive advice given to
older patients has the potential to increase healthy behaviours and alter health
outcomes. IMPLICATIONS: The annual health assessment items on the Medicare
Benefits Schedule, by enabling the GP to focus on prevention and coordination of
care, have the potential to improve the health, physical, psychological and
social function of older Australians.
PMID- 11011459
TI - Response rates of Victorian general practitioners to a mailed survey on
miscarriage: randomised trial of a prize and two forms of introduction to the
research.
AB - AIMS: To identify whether the form of introduction to a study and knowledge of a
substantial prize influence the response rate of general practitioners (GPs) to a
postal survey. METHODS: A postal survey of 700 randomly selected Victorian GPs
concerning management of early pregnancy bleeding and miscarriage, incorporating
two randomised-controlled trials of recruitment methods; analysis of response
rates and costs at 4 weeks and 11 weeks. RESULTS: The response rate was 61.5% of
eligible participants. Doctors made aware of a prize were more likely to respond
in the first four weeks (difference in response rate 10.2%, 95% confidence
interval (CI) 2.8%-17.6%). This difference diminished after the first four weeks.
Doctors introduced to the survey by a telephone call were no more likely to
respond than those introduced by a postcard. The use of a postcard saved 73% of
the cost of introducing the survey by telephone. Female doctors were more likely
than males to reply (difference 12.3%, 95% CI 4.7%-19.9%). Rural doctors were no
more likely to reply than urban doctors. Very few doctors (16.2%) completed a
Practice Assessment activity associated with the survey. CONCLUSIONS: A valuable
prize will accelerate response to a survey by GPs, thereby reducing the costs of
follow-up. The cost of telephoned introductions is not justified, when compared
with a brief written introduction.
PMID- 11011460
TI - Socioeconomic correlates of mortality differentials by local government area in
rural northern New South Wales, 1981-1995.
AB - OBJECTIVE: Many studies have examined the correlation between socioeconomic
status (SES) and mortality in Australia, but little is known about the
correlation in rural areas and most studies have not explored the trends in SES
differentials in mortality. This ecological study examines this correlation and
explores the impact of the national strategies to reduce SES differentials in
mortality in a rural area. METHODS: Mortality data for residents in the New
England Health Area, New South Wales (NSW), 1981 to 1995, were analysed. Twenty
Local Government Areas (LGAs) in New England were ranked and aggregated into 4
groups according to a composite SES indicator from the 1996 census, and age/sex
adjusted mortality rates were calculated for each group and compared. Poisson
regression models were used to assess the linear trends in mortality for 1981-95.
RESULTS: A strong relationship between working age adult mortality and SES was
found for both sexes. The rates for the most disadvantaged LGAs were
significantly higher than the least disadvantaged LGAs for both sexes. The
mortality rate was consistently higher for the most disadvantaged LGAs than the
least disadvantaged LGAs. CONCLUSION AND IMPLICATION: Although there has been an
overall decline in death for all 4 groups of LGAs, the gap between the most
disadvantaged and the least disadvantaged groups has widened over the last 15
years. This widening gap in death rates suggests that the strategies implemented
as part of the Health for All initiative to reduce inequalities in mortality
differentials have not been effective in this rural area.
PMID- 11011461
TI - More or less equal? Comparing Australian income-related inequality in self
reported health with other industrialised countries.
AB - OBJECTIVE: To measure the distribution of self-reported health by income in order
to compare the level of health inequality in Australia with other industrialized
countries. METHOD: Using data from the two National Health Surveys undertaken in
1989-90 and 1995, concentration indexes were calculated to quantify the
distribution of self-reported health by equivalent income. The concentration
index for Australia was compared with those reported for nine industrialized
countries in Europe and North America. RESULTS: The estimated income-related
concentration indexes were -0.1172 in 1989-90 and -0.1094 in 1995. CONCLUSION:
The level of health inequality is not significantly different from the US or the
UK, but significantly greater than seven other European nations. IMPLICATIONS:
Australia has significant income related health inequalities and the distribution
of health appears to be more unequal than in many other industrialized nations.
There is a need to further investigate and quantify those features of the
anglophone societies that set them apart from some other industrialized nations.
PMID- 11011462
TI - Queenslanders' use of personal strategies to minimise risk of mosquito-borne
disease.
AB - OBJECTIVE: To describe Queenslanders' awareness, knowledge and attitudes towards
mosquito-borne diseases and their transmission, and to determine which factors
influence the adoption of effective individual prevention strategies. METHODS: In
1995-6, cross-sectional surveys of adult residents in the western suburbs of
Brisbane and registered voters in Cairns were conducted. Forced entry logistic
regression was used to predict use of personal protection and elimination of
domestic breeding sites in the two cities. RESULTS: Final sample sizes were 347
in Cairns and 165 in Brisbane with response rates of approximately 70%. RRVD
awareness was nearly universal in both cities. A majority of residents (60% in
Brisbane and 65% in Cairns) report they are careful to avoid being bitten by
mosquitoes. 25% of Cairns residents and 18% of Brisbane residents report always
using some method of personal protection. Cairns residents are also more likely
to say that they actively prevent mosquitoes from breeding in their yards (76% in
Brisbane and 87% in Cairns). Knowledge of mosquitoes and disease transmission was
slightly higher in Cairns. In Brisbane, dislike of mosquitoes and being regularly
bitten were significant in the multivariate model predicting personal protection,
whereas concern for disease and being female were significant in Cairns. Concern
about disease was a significant predictor of eliminating breeding sites in both
cities. CONCLUSIONS: Raising concern about mosquito-borne disease can increase
use of personal prevention strategies. However, providing information on
prevention strategies may not be effective. The most effective strategies are not
practiced or seen by the public to be related to minimising risk of disease.
IMPLICATIONS: Greater emphasis in health promotion campaigns should be placed on
encouraging permanent alterations to the domestic environment rather than
temporary methods that are difficult to sustain and not effective against the
common vectors for mosquito-borne diseases in Queensland. Educational messages
should explicitly link preventive behaviours with the reduction in the likelihood
of contracting a serious disease.
PMID- 11011463
TI - Collecting and using aboriginal health information in New South Wales.
AB - OBJECTIVE: To describe the development of guidelines for the management of
Aboriginal health information in NSW. The purpose of the guidelines is to promote
the ethical management of Aboriginal health information, with appropriate
consideration for cultural factors. METHODS: The guidelines were developed
collaboratively by the NSW Aboriginal Health Partnership, which comprises NSW
Health (the central administrative office, named NSW Department of Health, and
the Area Health Services) and the NSW Aboriginal Health and Medical Research
Council (AHMRC), the peak body representing member Aboriginal Community
Controlled Health Services in NSW. A lengthy and comprehensive consultation
process enabled a wide range of interested groups to have input into the
guidelines. RESULTS: The project culminated in the production of the NSW
Aboriginal Health Information Guidelines, covering the collection, ownership,
storage, security, release, usage, interpretation and reporting of information,
as well as issues of privacy and confidentiality. The Guidelines formed the basis
of a formal Memorandum of Understanding, signed by the NSW Minister for Health,
NSW Department of Health and the AHMRC, on 24 August 1998. CONCLUSIONS AND
IMPLICATIONS: The Guidelines make an important contribution to meeting a need for
protocols on the collection, ownership and use of Aboriginal health information.
Their production reflects successful collaboration between government and
Aboriginal Community Controlled Health Services in NSW. Future reviews of the
Guidelines will ensure their effectiveness and consistency with Aboriginal
community principles.
PMID- 11011464
TI - Reproductive health, infertility and sexually transmitted infections in
indigenous women in a remote community in the Northern Territory.
AB - OBJECTIVE: To investigate markers of reproductive health in a remote Indigenous
community in Northern Australia. METHODS: A retrospective, cross-sectional
analysis of case notes of 342 women between the ages of 20 and 45 years, living
in one community in a remote region of the Northern Territory. RESULTS: The total
rate of current infertility in the community was 26.3%; 8.2% for primary
infertility and 18.1% for secondary infertility. An additional 3.3% of women had
resolved infertility. Only 43% of the women had sought medical help for the
problem. A history of ectopic pregnancy was recorded in 2.6%, stillbirth in 1.8%,
miscarriage in 14.3% and neonatal death in 12.3%. Depot steroidal contraception
or tubal ligation were used by 50% of the women but 45.9% used no contraception.
A history of pelvic inflammatory disease (PID), T. vaginalis N. gonorrhoeae,
genital C. trachomatis infection, syphilis or bacterial vaginosis was noted in
32%, 46%, 27%, 30%, 41% and 9% respectively. Current alcohol consumption was
reported in 23% and cigarette smoking in 76%. In multivariate analysis,
infertility was strongly associated with PID (adjusted OR 8.5), alcohol
consumption (AOR 3.1), T. vaginalis (AOR 2.5), N. gonorrhoeae (AOR 2.2) and
bacterial vaginosis (AOR 2.9). CONCLUSION: Reproductive health is poor in this
community of Indigenous women, with endemic levels of STDs, PID and tobacco
consumption. The absence of barrier contraception (e.g. condoms, diaphragms) has
implications for HIV and STD control. Clinical and public health interventions
are urgently required but the implementation of these is hindered by a number of
structural, social and economic barriers.
PMID- 11011465
TI - Drowning and alcohol in New Zealand: what do the coroner's files tell us?
AB - OBJECTIVE: To provide a systematic review of the details on alcohol involvement
available in the coronial files to determine if there is enough evidence to
estimate the role of alcohol in drowning. METHOD: We reviewed the coroner's files
of persons 10 years or older who drowned in New Zealand between 1992-1994
inclusive. RESULTS: A total of 320 coroner's files were examined. Blood Alcohol
Concentrations (BACs) were taken in 115 cases (36%) and positive for 50% of
these. When accounting for the incomplete testing by using all the information on
alcohol involvement collected, between 30-40% of the cases were estimated to have
a positive BAC and between 17-24% to have a BAC 100 mg/dL or higher. CONCLUSION:
The quality and completeness of current coronial information on alcohol
involvement in drowning is insufficient to arrive at an accurate estimate of the
percentage of drownings where alcohol was a factor. IMPLICATIONS: Coroners should
test drowning victims 10 years and older for BAC. These data should be
systematically recorded and processed with the goal of determining who should be
targeted in drowning and alcohol prevention programs.
PMID- 11011466
TI - The pattern of diabetes care in New South Wales: a five-year analysis using
Medicare occasions of service data.
AB - OBJECTIVE: To use Medicare occasions of service data to establish the pattern and
standard of care received by people with diabetes. METHOD: Information about
visits to medical practitioners as well as utilisation of diabetes related
procedures for people living in New South Wales (NSW) for the individual years
between 1993 to 1997 was retrieved using a Health Insurance Commission data file.
Individuals were deemed to have diabetes if an HbA1c which can only be ordered
for a person with known diabetes, had been performed over the five-year period.
RESULTS: On average over the study period, persons with diabetes accounted for
3.1% of the population but they used 5.5% of general practitioner services. A
large proportion of patients also received care at the specialist and consultant
physician level, 51.2% and 38.6% respectively, a three to four fold increase when
compared with their non-diabetic counterparts. There was also a 1.3 to 1.8 fold
increase in the mean number of attendances to the various medical practitioners.
Surveillance of diabetes parameters was inadequate but small improvements were
seen over the 5 year study period (proportion of persons with diabetes with a
HbA1c performed: 48.8% to 56.8%; Lipids: 49.4% to 52.0%; HDL cholesterol: 18.3%
to 18.8%; microalbuminuria: 4.7% to 11.6%). CONCLUSION: This study has
highlighted the heavy burden imposed by diabetes on our health care system.
IMPLICATIONS: The use of Medicare occasions of service data represents a cost
efficient way of monitoring health service utilisation.
PMID- 11011467
TI - Sites for depression on the web: a comparison of consumer, professional and
commercial sites.
AB - OBJECTIVE: To provide information on the range of treatments for depression
provided by commercial, professional and consumer web sites. METHODS: An audit of
the 21 most popular depression sites on the world wide web undertaken from March
1999 to July 1999, in Canberra, ACT. Treatment types and categories of treatment
were compared among commercial, professional and consumer web sites. RESULTS: A
total of 53 treatments or treatment types were mentioned. The number of
treatments mentioned per site ranged from 2 to 38. Antidepressant medication and
psychotherapy were noted by almost all sites. Consumer sites mentioned
psychological therapies less frequently but did not mention dietary supplements
or complementary treatments more frequently. CONCLUSIONS AND IMPLICATIONS:
Consumer web sites provide a point of comparison to those from commercial or
professional sources. They provide a voice to inform psychiatrists and GPs about
preferred treatments and side effects and to alert researchers to areas that need
formal investigation.
PMID- 11011469
TI - A workforce survey of health promotion education and training needs in the state
of Victoria.
AB - OBJECTIVE: This study investigates the education and training needs of health
professionals and factors affecting participation in education and training.
METHODS: A survey of health promotion professionals, health professionals, GPs
and CEOs of community health centres, conducted across different settings and
locations. Information was obtained on: involvement in health promotion
activities, most useful content and format of past training, current preferences
for education and training and barriers and incentives to education and training.
RESULTS: Health promotion professionals were involved in the widest variety of
health promotion activities, including more evaluation, research and planning
than GPs and other health professionals who were involved in more client-focussed
activities. Professionals' preference for training content reflected the type of
activities in which they were most frequently involved. Practical courses, of
short duration, delivered by experienced peers or health promotion experts were
preferred over university and TAFE courses. Professionals in rural and provincial
locations require both greater access to information on training and conveniently
located training. More organisational support, funding and time release would
encourage the training of professionals in government departments, community
health centres and public hospitals. CONCLUSIONS: To be most effective, training
must be tailored to suit the specific needs of different professionals involved
in health promotion and take into consideration how factors, such as financial
incentives and time release, influence participation across different settings
and locations. IMPLICATIONS: Further development of the health promotion
workforce will require recognition of its professional diversity and a more
responsive and organised approach to education and training programs.
PMID- 11011468
TI - Sharing obstetric care: barriers to integrated systems of care.
AB - OBJECTIVES: To map the provision of shared obstetric care in Victoria, and
investigate the views of care providers about the ways in which current practice
could be improved. METHOD: All Victorian public hospitals with > or = 300 births
per annum and a purposive sample of hospitals with < 300 births per annum were
mailed a questionnaire seeking information about current practice. Interviews
with key informants (n = 32) were conducted at four case study sites. RESULTS:
The response rate to the hospital survey was 98% (42/43). Fourteen different
models of shared care were identified. Two-thirds of hospitals with > or = 300
births per annum (16/28) had three or more different models of shared care. Six
hospitals (15%) had written guidelines for all models of shared care offered; 13
(32%) had written guidelines covering some models. Practice varied considerably
in relation to: exclusion criteria, recommended schedule of visits and use of
patient-held records. There was little consensus about the content of visits and
responsibility for covering particular aspects of care. Few hospitals (6/42) had
written information for women about shared care. Care providers expressed
divergent views regarding the question of where ultimate responsibility lies for
individual patient care and for the overall management of shared care.
CONCLUSIONS: Current funding arrangements provide strong incentives to expand
enrollment in shared obstetric care. Expansion of shared care has occurred
without the development of formal, consultative and agreed arrangements between
providers, or adequate provision for monitoring, evaluation and review. The
variety, complexity and fluidity of models of shared care and lack of agreed
procedures contribute to difficulties experienced by both providers and women
participating in shared care. IMPLICATIONS: Detailed evidence-based agreed
guidelines developed in consultation with hospital and community providers, and
provision of improved information to women about what to expect in shared care
arrangements are urgently required.
PMID- 11011470
TI - Cigarette smoking, menstrual symptoms and miscarriage among young women.
AB - OBJECTIVE: To examine associations between cigarette smoking and menstrual
symptoms and miscarriage among young women. METHOD: The study sample consists of
14,779 women aged 18-23 years who participated in the mailed baseline survey for
the Australian Longitudinal Study on Women's Health, conducted in 1996. The main
outcome measures are self reported menstrual symptoms and miscarriages. RESULTS:
Current smokers and ex-smokers had an increased risk of menstrual symptoms and
miscarriages compared with women who had never smoked, with the highest risk
occurring in heavy smokers (adjusted odds ratios for those smoking > or = 20
cigarettes per day: premenstrual tension 1.5 (95% confidence interval 1.3 to
1.7), irregular periods 1.5 (1.3 to 1.8), heavy periods 1.6 (1.4 to 1.9), severe
period pain 1.5 (1.4 to 1.7), one or more miscarriages 2.0 (1.5 to 2.8). The odds
ratios generally increased with numbers of cigarettes smoked and a younger age of
starting to smoke. CONCLUSION: This study suggests that young women who smoke are
at higher risk of a range of menstrual problems and miscarriage than those who
have never smoked. The immediacy of this risk (in contrast to the longer term
risks of chronic disease) can be used to improve the relevance of anti-smoking
campaigns targeted to young women.
PMID- 11011471
TI - Cohort trends in the age of initiation of drug use in Australia.
AB - AIM: To examine birth cohort trends in the prevalence of use and the age of
initiation of use of: alcohol, tobacco, cannabis, amphetamines, LSD, and heroin.
METHOD: Data were taken from the 1998 National Drug Strategy Household Survey, a
survey of a representative sample of Australians aged 14 years and over. Nine
five-year cohorts were examined among persons born between 1940 and 1984. The
weighted prevalence of use by ages 15 years, 21 years, and lifetime use, was
estimated, as was the average age of first use among users. The significance of
trends was tested using logistic regression (for lifetime use, use by 15 and 21
years) and linear regression (for age of first use). RESULTS: Lifetime prevalence
of alcohol and tobacco use was similar among all birth cohorts. The prevalence of
illicit drug use--cannabis, amphetamines, LSD and heroin--increased with
successive birth cohorts and more recent birth cohorts reported using licit and
illicit drugs at a younger age. CONCLUSIONS: More recent cohorts are more likely
to use illicit drugs at some point in their lives. Greater numbers of persons
from more recent birth cohorts may be at risk of developing substance-related
problems.
PMID- 11011472
TI - Systematic review processes and the management of opioid withdrawal.
AB - OBJECTIVE: To assess the diversity of research on the management of opioid
withdrawal, identify sources of heterogeneity and provide a context for
subsequent systematic reviews to establish evidence-based best practice. METHODS:
References were identified through searches of multiple electronic databases and
handsearching the reference lists of retrieved articles. The principal criterion
for inclusion in the literature mapping process was that it be a study of an
intervention intended to manage the process of opioid withdrawal. RESULTS: Of 218
references assessed, all participants were dependent on heroin in 41% and on
methadone or l-alpha acetyl methadol (LAAM) in 24%. More than 17 different types
of treatment approach were identified. Only 42% of references used a rating
instrument to assess withdrawal severity and reported sufficient results to
indicate the timing and magnitude of the peak and/or duration of withdrawal. The
type of rating instrument used and the way in which results were reported varied
enormously. A clear parameter for completion of detoxification was used for 37%
of references. CONCLUSIONS: The capacity for rigorous systematic reviews of the
management of opioid withdrawal is currently limited. There are multiple sources
of heterogeneity that will need to be taken into account. IMPLICATIONS: The use
of narrative reviews and observational studies are important complements to
formal systematic reviews in the establishment of evidence-based practice in any
area that combines aspects of psychology, behaviour, social context and medical
treatment.
PMID- 11011473
TI - Bilateral health aid: lessons from Europe.
AB - OBJECTIVE: The objective of this study is to document current issues in policy
and planning for development assistance in health from the perspective of key
bilateral aid donors in Europe, and to explore its relevance for Australia.
METHODOLOGY: This study is based on seventy-seven interviews and documentary
analysis undertaken between July and December 1999 with policy, technical and
field staff of major European bilateral aid donors, the World Health Organisation
(WHO), and key academic institutions. Notes were taken of interviews, and
relevant documentation collected. Forty-five key interviews were tape recorded
and transcribed for analysis. RESULTS: The shift towards program and Sector Wide
Approaches in development assistance reflects broader political changes in Europe
since the collapse of the Communist block. Increasingly, achieving an impact on
poverty is seen as linked to better governance, improved policy frameworks, and
collaboration between donors and partner governments, and between donors
themselves, reflected in the broad support for Sector Wide Approaches to
development assistance. CONCLUSIONS: These perspectives bring new demands to
donors such as Australia: structural changes, procedural changes, collaborative
approaches to programs, closer relationships with counterparts. IMPLICATIONS: The
uncertainty in which health sector reform operates necessitates a reflective and
adaptive approach to management of aid, and responsiveness to monitoring and
evaluation and the development of new knowledge. Given Australia's strategic
positioning in its sphere of influence, the experience from Europe should inform
the development of our own future directions.
PMID- 11011474
TI - Smoking among ethnic Chinese patients and their recall of quit advice by Chinese
speaking general practitioners in Sydney.
AB - OBJECTIVES: To collect smoking-related data from Chinese patients attending
Chinese-speaking general practitioners (CSGPs), including self-reported smoking
status, recall of a question about smoking status during the previous six months
by their GP and, for smokers, their recall of quit advice in their most recent
consultation. DESIGN: Descriptive research first involving self-administered
waiting-room questionnaires and, afterwards, a second self-administered
questionnaire to examine behaviour in that most recent consultation. SETTING:
Surgeries of 24 CSGPs in Central Sydney. SUBJECTS: 1084 Chinese patients aged 18
70 years. RESULTS: Self-reported smoking prevalence was 25% (95% CI: 21%-29%) for
men and 4% (95% CI: 2%-5%) for women. Of 103 smokers who had visited their
regular GP during the previous 6 months, 42% recalled a question about smoking
status and 38% quit advice. As elicited at follow-up, 72% recalled any discussion
in their most recent consultation about smoking although effective techniques
were rarely recalled. Patient's sex (OR: 1.78; 95% CI: 1.28-2.47) and smoking
status (OR: 1.39; 2.38; 95% CI: 0.85-2.25, 1.49-3.81) independently predicted a
question about smoking status. Among smokers, marital status was the only
independent predictor of quit advice. As assessed by a stage-of-change scale,
significantly more Chinese smokers were not ready to contemplate cessation,
compared with Angio-Celtic community survey results. CONCLUSIONS: Our study
provides unique information about smoking among ethnic Chinese patients attending
CSGPs. Findings also suggest CSGPs need greater support to maximize their
clinical opportunities to advise Chinese smokers to quit.
PMID- 11011476
TI - The turmoil of aboriginal enumeration: mobility and service population analysis
in a central Australian community.
AB - This paper documents Aboriginal population change and mobility over time in a
remote community in central Australia. The movement of population has
implications for service delivery and resource allocation. Aboriginal population
in the region is characterised by high mobility. We conducted four population
surveys in a selected remote community over a 12 month period and categorised
individuals into four mutually exclusive groups: residents, dual residents,
visitors and absent residents. Based on these categories we developed two
population classifications: actual and potential service populations. The
potential service population was consistently higher than the Australian Bureau
of Statistics (ABS) census figure. We question the use of ABS census estimates as
appropriate population figures for determining resource allocation to remote
communities. We quantify inter- and intra-community mobility. When the potential
population is used as denominator, 35% of the population of this community was
classified as inter-community mobile. Given this level of mobility we argue that:
(1) Resources should be allocated to compensate health services for the
additional time and resource requirements to deal with the high level of
population mobility. (2) Health programs such as STD control, trachoma, scabies
and other communicable diseases common in Central Australia should be coordinated
and delivered as regional programs often crossing State/Territory borders.
PMID- 11011475
TI - A general practice-based recruitment strategy for colorectal cancer screening.
AB - OBJECTIVE: To determine whether a screening recruitment strategy for first degree
relatives of people with colorectal cancer is effective in enabling eligible
relatives to request screening from their general practitioner (GP) and to assess
acceptability to GPs and patients. METHODS: Thirty GPs, from 26 practices, and
303 of their patients aged over 50 who were first degree relatives of a person
with colorectal cancer, participated in a randomised controlled trial of a GP
based recruitment strategy, in the Newcastle Area of New South Wales, Australia.
RESULTS: The proportion of relatives requesting screening was statistically
significantly higher in the intervention group than in the control group (18%
compared to 4%, respectively; p = 0.01). CONCLUSIONS: Interest in the study by
GPs was low, however for GPs who were involved, the recruitment strategy did
prompt first degree relatives to discuss screening. The strategy may be even more
effective when combined with other interventions such as a media campaign. The
results may be generalizable to feasibility studies of general population
screening for colorectal cancer in Australia. IMPLICATIONS: The results of this
work are potentially informative to public health practice in Australia given the
ensuing pilot programs of colorectal cancer screening.
PMID- 11011477
TI - Researching health care and public policy.
PMID- 11011478
TI - Do women have equitable access to quality breast prosthesis services?
AB - Although up to 90% of women who have had a mastectomy use breast prostheses,
significant gaps exist around current breast prosthesis services for Australian
women. These gaps include the timeliness and quality of information provision,
the disparity in financial assistance, and the lack of knowledge regarding the
determinants of what constitutes a "quality" breast prosthesis. Revised policy
initiatives are central to addressing these gaps to ensure equitable access to
quality breast prosthesis services.
PMID- 11011479
TI - The long-term factors associated with removal from parents amongst indigenous
prisoners in NSW.
PMID- 11011480
TI - Smoke rings around the Olympics.
PMID- 11011481
TI - A randomised trial of telephone versus postcard prompts to enhance response rate
in a phased population-based study about community preferences.
PMID- 11011482
TI - Long-term ventilating tube with tympanosclerosis.
PMID- 11011483
TI - Pedunculated granuloma of the vocal fold.
PMID- 11011484
TI - Endoscopic views of nasal septal polyps.
PMID- 11011485
TI - Electronystagmography: dizziness and syncope.
PMID- 11011486
TI - Giant-cell reparative granuloma.
PMID- 11011487
TI - Are we all just stupid?
PMID- 11011488
TI - Nasal congestion: a review of its etiology, evaluation, and treatment.
AB - The most common clinical syndromes that cause nasal congestion are allergic
rhinitis, vasomotor rhinitis, chronic sinusitis, and upper respiratory viral
infections (common colds). Nasal congestion, in turn, can lead to sequelae such
as sinusitis, otitis media, and the onset or worsening of mild to severe sleep
disturbances, including obstructive sleep apnea. There is a host of conservative
treatments, including decongestant pharmacotherapy, antiallergy measures, and
nasal dilation devices. Several surgical procedures are also available. This
article reviews the current guidelines for the workup and diagnosis of nasal
congestion and briefly describes the many and varied approaches to treatment.
PMID- 11011489
TI - Audiometric manifestations of Waardenburg's syndrome.
AB - We studied 23 patients (from 11 families) who had Waardenburg's syndrome.
Patients were evaluated by conventional audiometric methods and by distortion
product otoacoustic emissions to determine the penetrance and the degree and type
of hearing loss. Twelve of the patients had the type I form of the syndrome and
11 had type II. Overall, we found hearing loss in 19 of the 23 patients (83%);
hearing loss affected nine type I patients (75%) and 10 type II patients (91%).
Five type I patients (42%) and eight type II patients (73%) had a hearing loss of
> 100 dB. Bilateral symmetrical hearing loss was the most common type of loss, as
it was seen in six of the type I patients (50%) and eight of the type II patients
(73%). At lower frequencies, distortion-product otoacoustic emission amplitudes
were found to be significantly above the noise floor in five of the 11 patients
whose hearing thresholds were 60 dB HL or worse by click auditory brainstem
response testing. These findings led us to conclude that it is necessary to use
otoacoustic emissions in patients with Waardenburg's syndrome in order to provide
optimum fitting of hearing aids, especially in children.
PMID- 11011490
TI - Unplanned admissions following outpatient otologic surgery: the University of
Arkansas experience.
AB - We analyzed the outpatient otologic surgery experience at our institution to
identify those factors that are associated with a high risk of postoperative
complications that require an unplanned hospital admission. We found that among a
group of 662 patients who underwent group II otologic procedures (i.e.,
tympanoplasty with or without mastoidectomy, stapedotomy, and middle ear
exploration), the overall admission rate was 4.7%, of which 3.9% were unplanned.
A significantly larger percentage of children were admitted than adults (5.7 vs.
2.3%), primarily for nausea and vomiting. Three factors were significantly
associated with unplanned admissions: the type of surgery (tympanomastoidectomy
with ossicular reconstruction), the duration of general anesthesia (> 2 hr), and
asthma as a coexisting condition. The choice of antiemetic administered
(ondansetron or droperidol) and the specific agents used for general anesthesia
did not appear to have any significant impact on unplanned admissions. We
recommend that the three predisposing factors be taken into consideration when
formulating the treatment plan. Scheduling an inpatient procedure for patients
who have risk factors for complications requiring hospitalization would avoid the
extra costs and stress associated with unplanned admissions.
PMID- 11011491
TI - Giant benign sinonasal squamous papilloma: report of a case.
AB - We treated a patient with a giant squamous papilloma in the nasal cavity and
maxillary sinus that extended through a bony defect into the oral cavity. The
mass was excised with a combined endoscopic, Caldwell-Luc, and transoral
approach. Lesions of this type are rare, but when they do occur, the rate of
recurrence is high. Therefore, long-term followup, including endoscopic
examination, is important.
PMID- 11011492
TI - A new ligation approach to the management of chronic epistaxis.
AB - Standard cauterization therapy for chronic epistaxis is less than ideal because
of the inadequacy of topical anesthesia and the difficulty of treating young,
often uncooperative patients. The author has developed a new procedure for
treating these patients, which entails ligation and cauterization while the
patient is under light general anesthesia in an outpatient surgical facility. Of
the approximately 75 procedures the author has performed, only one failed to
achieve expected results. This article describes how this safe, simple, and
ultimately cost-effective procedure is performed.
PMID- 11011493
TI - Nasopharyngeal cyst of branchiogenic origin: report of a case and review of the
literature.
AB - To date, only 22 cases of nasopharyngeal cyst of branchiogenic origin have been
reported in the literature. In this article, we report a new case in a 35-year
old woman. We also present a review of the literature and a discussion of the
sites of origin, histopathology, and treatment modalities.
PMID- 11011495
TI - Primary non-Hodgkin's lymphoma of the frontal sinus: how we diagnosed it.
AB - Isolated primary non-Hodgkin's lymphoma of the frontal sinus is rare. We describe
the case of a middle-aged man who came to us with signs of orbital cellulitis
complicating an acute infected frontal mucocele. His condition was initially
controlled with medical therapy and subsequent endoscopic sinus surgery, but his
symptoms eventually returned. We were able to diagnose the lymphoma only by
approaching the sinus externally to obtain a biopsy. This case highlights the
importance of making a full visual inspection of the involved sinus in order to
avoid missing an unexpected, albeit a rarely encountered, pathology.
PMID- 11011494
TI - Canalith repositioning for benign paroxysmal positional vertigo: a randomized,
controlled trial.
AB - We assessed the efficacy of the canalith repositioning maneuver by comparing it
with no treatment in a population of patients with benign paroxysmal positional
vertigo (BPPV). In this randomized, controlled, 6-month efficacy trial, outcomes
were measured subjectively by patients' reports of symptom status and objectively
by Hallpike testing. During the first month of the study, the treated group
experienced significantly better outcomes than did the control group, but this
trend was not sustained at 3 and 6 months.
PMID- 11011496
TI - In memoriam: Martin T. Orne, 1927-2000.
PMID- 11011498
TI - Descriptive outcomes of the American Lung Association of Ohio hypnotherapy
smoking cessation program.
AB - Hypnosis smoking cessation treatment is one type of program available to smokers.
This paper describes a large randomly selected sample from such a program, which
has not been previously reported. During 1997, 2,810 smokers participated in
single-session, group hypnotherapy smoking cessation programs sponsored by the
American Lung Association of Ohio. A randomly selected sample of 452 participants
completed telephone interviews 5 to 15 months after attending a treatment
session. Twenty-two percent of participants (n = 101) reported not smoking during
the month prior to the interview. Use of other smoking cessation strategies since
the treatment session were assessed. Interestingly, only 20% of participants who
used pharmaceutical products to assist with smoking cessation took them for the
recommended treatment duration. Hypnotherapy smoking cessation treatment offers
an alternative cessation method, which may meet the unique needs of certain
individuals.
PMID- 11011497
TI - Specific autobiographical memory following hypnotically induced mood state.
AB - This study investigated the impact of hypnotically induced mood on the
specificity of autobiographical memory. High (n = 24) and low (n = 21)
hypnotizable participants were administered a hypnotic induction for sad,
neutral, or happy mood and were asked to retrieve specific autobiographical
memories in response to positive and negative cue words. Whereas high
hypnotizable participants in the sad condition provided fewer specific memories
in response to positive rather than negative cues, those in the neutral and happy
conditions responded similarly to positive and negative cues. Findings suggest
that impaired recall of specific memories may be mediated by state factors
associated with sad mood. These results point to the utility of hypnotic mood
induction as a means to experimentally investigate the relationship between mood
and autobiographical memory.
PMID- 11011499
TI - Autonomic and psychological responses to an acute psychological stressor and
relaxation: the influence of hypnotizability and absorption.
AB - This study examined the influence of hypnotizability and absorption on
psychological and autonomic responses to an experimental stressor and a
relaxation procedure of 13 high and 13 low hypnotizable subjects. Heart-rate
variability was the measure of autonomic reactivity. Absorption was found to be
the only significant predictor of autonomic reactivity in both experimental
conditions. Expectation and previous relaxation training, but not absorption or
hypnotizability, predicted perceived relaxation in the relaxation condition. The
results suggest that in a nonhypnotic context the influence of hypnotizability on
responses to experimental conditions may be less prominent than the influence of
absorption. Absorption may be associated with greater awareness of internal
physical and psychological processes, and the results support previous clinical
findings of positive correlations between absorption, subjective perception of
autonomic arousal, and somatic symptom reporting.
PMID- 11011500
TI - Goal-directed fantasy does not explain the training effect of the Carleton Skills
Training Package.
AB - Two treatments to enhance the hypnotic responsiveness of subjects who pretested
as low in hypnotic susceptibility were compared. Subjects in one modification
treatment (n = 20) received the Carleton Skills Training Package (CSTP). Those in
a second modification treatment (n = 20) were administered a partial training
that did not include information about imaginal strategies. The authors of the
CSTP assume that goal-directed fantasies underlie subjects' feelings of
involuntariness, so teaching imaginal strategies is the primary agent of
subjective changes after the training. Controls (n = 20) received no treatment.
Both training packages enhanced behavioral and subjective response to an
equivalent degree. Control subjects' performances were stable across tests.
Modest increases in hypnotizability scores following training were related
neither to enhancing goal-directed fantasies nor to use of imagery. Other
mechanisms, possibly compliance, may underlie the CSTP effect.
PMID- 11011501
TI - Ericksonian approaches to hypnosis and therapy: where are we now?
AB - Ericksonian approaches to psychotherapy and hypnosis have had a significant
impact on many clinical practitioners over the last two decades. This article
reviews the current empirical research with regard to the efficacy of these
treatment approaches as well as for the key Ericksonian assumptions of: (a)
belief in an altered state of consciousness and the existence of specific markers
indicating an altered state; (b) the superiority of indirect suggestion over
direct suggestion; and (c) client hypnotizability is a function of the
hypnotist's skill. The current literature provides empirical support neither for
efficacy nor for these key assumptions. The article concludes with a discussion
of the need for empirically based research to test the efficacy of Ericksonian
therapy and its core components, lest this approach become isolated from the
scientific hypnosis and therapy communities.
PMID- 11011502
TI - Where Ericksonian legend meets scientific method: a comment on Matthews.
PMID- 11011503
TI - The effect of union type on psychological well-being: depression among cohabitors
versus marrieds.
AB - Marital status is a key determinant of psychological well-being. I use data from
both waves of the National Survey of Families and Households to evaluate the
effect of union type (i.e., cohabitation versus marriage) on depression.
Cohabitors report higher levels of depression than their married counterparts,
net of sociodemographic factors. The greater depression characterizing cohabitors
is primarily due to their higher relationship instability relative to marrieds.
Cohabitors' reports of relationship instability are about 25 percent higher than
marrieds' reports. High levels of relationship instability are especially
detrimental for cohabitors who have been in their union for a long period of
time. Additionally, cohabitors' depression scores are exacerbated by the presence
of biological and step children, whereas marrieds' depression scores are
impervious to children. Longitudinal analyses that correct for selection bias
confirm that the lower levels of well-being characterizing cohabitors are not due
to the types of people who choose to cohabit.
PMID- 11011504
TI - Life stress, anger and anxiety, and delinquency: an empirical test of general
strain theory.
AB - General strain theory (Agnew 1992) departs from traditional strain theories by
emphasizing the role of the individual's affective responses to negative life
experiences in fostering deviant behavior. In this analysis, we examine the
central hypotheses of general strain theory using data from a three-wave panel
study of high school youths in the Boston metropolitan area (N = 939). Covariance
structure models reveal that anger and hostility in response to negative life
events do play a causal role in fostering more aggressive forms of delinquency,
but are not significantly related to either nonaggressive delinquency or
marijuana use. Furthermore, the conditional effects predicted by general strain
theory, in which the impact of strain on delinquency varies by youths' personal
and social resources, are inconsistent. Discussion centers on the prospect of
increasing the utility of general strain theory by further imbuing it with
concepts and perspectives from the sociology of mental illness.
PMID- 11011505
TI - Alcohol and employment in the transition to adulthood.
AB - We elaborate the relationship between work hours and alcohol use during the
transition from adolescence to adulthood. Both hours of employment and drinking
may be products of weak bonds to school and family. Alternatively, work may exert
an independent effect on alcohol use by exposing adolescents to opportunities and
associates that facilitate drinking. Using longitudinal data from the Youth
Development Study (YDS), we present static score regression models showing that
long work hours increase levels of drinking during high school. These effects are
mediated in large part by work-derived independence from parents, suggesting that
a precocious transition to adult roles may be the mechanism connecting work hours
and alcohol use. Work effects on drinking are short-lived, however, as adolescent
hours of employment do not significantly influence alcohol use after high school.
PMID- 11011506
TI - Perceived discrimination and depression among Mexican-origin adults in
California.
AB - We contend that perceived discrimination has an independent effect on depression
outcomes among adults of Mexican origin. Using a sample of 3,012 Mexican-origin
respondents in Fresno, California in 1995/96 (ages 18-59) we investigate the
direct and moderating connections between perceived discrimination, acculturative
stress, and mental health (CES-D). We also investigate the social patterning of
perceived discrimination. While more highly acculturated immigrant respondents
were more likely to experience discrimination than their less acculturated
counterparts, more highly acculturated U.S. born respondents were less likely to
experience discrimination. Discrimination was directly related to depression, but
this effect was moderated through nativity/country of residence, English-language
acculturation, sex, and country of education variables. Moderate levels of legal
status acculturative stress were especially depressive for native-born U.S.
residents.
PMID- 11011508
TI - Settlement has many faces: physicians, attorneys and medical malpractice.
AB - We conduct an analysis of the jurisdictional dispute over the management of
medical malpractice lawsuits, focusing on the process through which liability is
defined. We utilize a North Carolina sample of physicians who have been sued,
their defense counsel, and counsel for the plaintiff in the case. A comparison of
the perspectives of these three parties reveals that over half of the physicians
who settle perceive themselves as not liable. Defense counsel are more adept at
predicting both negotiated resolutions and whether or not money will be paid than
either plaintiffs' counsel or physicians. Almost two-thirds of physicians who
thought they were not liable expressed a desire for vindication. Almost half the
time when the physicians denied liability money was nonetheless paid to resolve
the claim. Physician responses to the outcome of their cases focus on the need
for reform, especially in terms of a call for peer or expert review. We identify
and discuss culture conflict between law and medicine. For lawyers "settlement"
is not a negative thing, but for physicians it implies fault. We challenge
existing literature which analyzes the settlement of medical malpractice claims
solely in terms of rational economic models, and we argue that social
psychological variables are equally important.
PMID- 11011507
TI - Unfair treatment, neighborhood effects, and mental health in the Detroit
metropolitan area.
AB - Why do racial differences in many indicators of mental and emotional well-being
show inconsistent patterns? We propose that mental and emotional well-being are
influenced by aspects of the social context, including experiences of unfair
treatment and the concentration of households with incomes below the poverty
level, and that differential exposure to these factors influences racial
differences in mental well-being. We analyze the reporting of psychological
distress and life satisfaction in a multistage area probability sample of 1,139
African American and white residents of the Detroit metropolitan area aged 18 and
older. Both psychological distress and life satisfaction are significantly
associated with exposure to unfair treatment and with the proportion of
households in the census block group that were below the poverty level. Racial
differences in psychological distress and life satisfaction were eliminated or
reversed once differentials in the percent of households living below the poverty
line and exposure to unfair treatment were accounted for. These findings
contribute to a growing body of evidence that "race" effects operate through
multiple pathways that include race-based residential segregation and its
attendant economic disinvestment at the community level, and interpersonal
experiences of unfair treatment.
PMID- 11011509
TI - Death makes news: the social impact of disease on newspaper coverage.
AB - This paper is an integrated analysis of newspaper coverage, epidemiological
rates, and recent social history of six prominent diseases. HYPOTHESES: Newspaper
coverage of a disease has three developmental stages (emergence, maturation, and
decline & death). Trends in newspaper coverage of a disease reflect trends in its
mortality, prevalence, and incidence. Magnitudes of newspaper coverage of
diseases reflect their differential mortality rates. DATA: Using the LEXIS-NEXIS
news archive for major U.S. newspapers, we retrieve articles about cancer, heart
disease, AIDS, diabetes, Alzheimer disease, and arthritis for the period 1977
1997. We also obtain mortality, prevalence, and incidence trends for the six
diseases. RESULTS: During the two decades, newspaper coverage emerges for AIDS
and Alzheimer disease and is in the mature stage for the other diseases; declines
begin for heart disease and AIDS. Trends in news coverage closely parallel
mortality trends, and less consistently prevalence and incidence trends. Sharp
downturns and upturns in mortality are mirrored in news volume. High-mortality
diseases prompt both the most news coverage and the largest proportions of
articles with death topics. CONCLUSION: Newspaper coverage of diseases is
responsive to their mortality levels and trends.
PMID- 11011510
TI - Homophone meaning generation: a new test of verbal switching for the detection of
frontal lobe dysfunction.
AB - Executive functions in their broadest sense may be impaired in patients with
frontal lobe lesions. The Wisconsin Card Sorting Test, perhaps the most robust
test sensitive to frontal lobe dysfunction, requires the flexibility to switch a
response pattern to meet the change in task demands. However this task has only
two category switches and normal respondents tend to score at ceiling. Verbal
fluency tasks also incorporate a switching component and it was hypothesized that
a word generation task that maximized a switching requirement might provide a
more satisfactory verbal measure of frontal lobe dysfunction. A new test of
homophone meaning generation that requires multiple switches between verbal
concepts (e.g., tick = insect, correct, etc.) was devised. Normative data was
obtained from a sample of 170 control participants. Seventy-one patients with
unilateral anterior or posterior cerebral lesions were also tested. A normal
distribution of scores was obtained in the standardization sample. The anterior
lesion groups were more impaired than the posterior groups. There were no
significant differences due to laterality. This homophone meaning generation task
is a measure of frontal lobe dysfunction that has the advantage of psychometric
properties that permit measurement of the degree of impairment.
PMID- 11011513
TI - Does literacy have an effect on stick construction tasks?
AB - Since constructional apraxia is often concomitant with brain lesions, the study
of constructional tasks in the non-brain-damaged population might be useful in
helping to disentangle other causal factors. This paper explores the performance
of illiterate individuals (N = 29) as compared to that of semiliterates (N = 21)
and literates (N = 23) in order to see the effect of reading and writing
abilities on constructional tasks. Each participant was asked to construct 4
figures based upon models having varying degrees of complexity. A global
criterion of lack of fidelity and several analytic criteria (related to
distortion, rotation, and disarticulation errors) were used to evaluate
performance. Although illiterates generally made more errors than semiliterates
and semiliterates more than literates, only some of these differences were
statistically significant. Significant differences were found for lack of global
fidelity and disarticulation errors when all 4 figures were considered together.
Subtler data emerged with respect to single figures.
PMID- 11011511
TI - The functional relevance of affect recognition errors in schizophrenia.
AB - To evaluate the clinical and ecological validity of affect recognition (AR)
measures in a sample of community-dwelling schizophrenic outpatients (N = 40), we
analyzed the relation of facial and vocal AR to intellectual, symptomatic, and
quality-of-life criteria. Facial and vocal AR showed virtually identical patterns
of association with these criteria, suggesting that both modalities of AR draw on
the same underlying heteromodal capacity. Specifically, AR was correlated with a
subset of intellectual abilities (verbal-semantic, executive-attentional), but
was unrelated to age, education, or neuroleptic dose. In terms of clinical and
ecological criteria, AR errors correlated with more severe psychotic symptoms
(positive and disorganized) and with lower quality of life (relationships,
community participation, and richness of intrapsychic experience). Even after
controlling for subjects' intellectual abilities and illness severity, inaccurate
AR was associated with bizarre behaviors (involving sociosexual interactions,
clothing, appearance) and with impoverished interpersonal relations. Thus, while
difficulty identifying basic affective cues is related to general cognitive and
illness-severity factors, it appears to have specific functional implications
that do not depend on generalized impairment. Assessment of AR may identify a
subgroup of schizophrenic patients who have a central defect in the heteromodal
monitoring of emotional-social displays, associated with dysregulation of social
behaviors and disruption of interpersonal relations.
PMID- 11011512
TI - Affective self-report during the intracarotid sodium amobarbital test: group
differences.
AB - Emotional reactions are sometimes observed during the intracarotid sodium
amobarbital test. For instance, euphoric/indifference reactions can be seen
during right hemisphere inactivation and catastrophic reactions may accompany
left hemisphere inactivation. Less dramatic changes can also be detected in
affective self-report during left and right hemisphere amobarbital tests, with
more negative affect reported during left hemisphere inactivation and either
neutral or mildly positive affective states reported during right hemisphere
inactivation. The current study not only replicated this effect, but in addition,
found significant group differences. The first group (right way) showed a pattern
of affective self-report during left and right amobarbital tests entirely
consistent with prior findings, while a second group (wrong way) showed results
that behaved in a diametrically opposite fashion. A third group (no change)
showed little, if any, difference in affective self-report during left and right
amobarbital tests. The major factor distinguishing the wrong way group from the
other two appeared to be an asymmetrical distribution of left and right temporal
lobe lesions in the former group. In contrast, the factor differentiating the
right way group from the no change group appeared to be the relative degree of
left hemisphere inactivation during the left hemisphere amobarbital test. The
results are discussed not only in terms of their impact on theories of cerebral
lateralization for emotion, but also in terms of methodological issues in this
field.
PMID- 11011514
TI - Characteristics of memory dysfunction in body dysmorphic disorder.
AB - Although body dysmorphic disorder (BDD) is receiving increasing empirical
attention, very little is known about neuropsychological deficits in this
disorder. The current study investigated the nature of memory dysfunction in BDD,
including the relationship between encoding strategies and verbal and nonverbal
memory performance. We evaluated 17 patients with BDD and 17 healthy controls
using the Rey-Osterrieth Complex Figure Test (RCFT) and the California Verbal
Learning Test (CVLT). BDD patients differed significantly from healthy controls
on verbal and nonverbal learning and memory indices. Multiple regression analyses
revealed that group differences in free recall were statistically mediated by
deficits in organizational strategies in the BDD cohort. These findings are
similar to patterns previously observed in obsessive-compulsive disorder (OCD),
suggesting a potential relationship between OCD and BDD. Studies in both groups
have shown that verbal and nonverbal memory deficits are affected by impaired
strategic processing.
PMID- 11011515
TI - Perception and estimation of time in long-term survivors of childhood posterior
fossa tumors.
AB - We examined short duration perception (400 ms), long duration estimation (30 and
60 min), and spatiotemporal estimation in long-term survivors of childhood
cerebellar tumors with a mean time since diagnosis of 14.2 years. Groups of
individuals with tumors treated with surgery only (astrocytoma, N = 20) were
compared to those with tumors treated with surgery, focal radiation, and
craniospinal radiation (medulloblastoma, N = 20), and to age-matched controls (N
= 40). Childhood lesions of the cerebellum produced enduring deficits in short
duration perception, but spared the ability to functionally estimate long
durations, regardless of the pathology or treatment of the tumor. Evidence did
not support any functional recovery over time of the cerebellar system that
underlies short-duration perception. Younger age at treatment was not a
protective factor. Although no group differences were present in the functional
measures of long-duration estimation, tumor-related prospective memory deficits
interfered with the ability to produce long-duration prospective estimates. The
utilization of sensory and somatomotor information to refine real-world
spatiotemporal estimates was compromised in the medulloblastoma group only.
PMID- 11011516
TI - Conceptual apraxia and semantic memory deficit in Alzheimer's disease: two sides
of the same coin?
AB - This study was designed to examine the patterns of apraxic disturbances and the
relationships between action knowledge and other measures of semantic knowledge
about objects in 10 well-characterized Alzheimer's disease (AD) patients. Five
tasks were used to assess components of action knowledge (action-tool
relationships, pantomime recognition, and sequential organization of action) and
praxis execution (actual use, pantomiming) according to the cognitive model of
praxis. Three tasks (verbal comprehension, naming, and a visual semantic matching
task) were used to assess verbal-visual semantics. Considering patterns of
apraxia first, conceptual apraxia was found in 9 out of the 10 AD patients,
suggesting that it is a common feature even in the early stages of AD. Second, we
found partly parallel deficits in tests of action-semantic and verbal-visual
semantic knowledge in 9 AD patients. Impaired action knowledge was found only in
patients with a semantic language deficit. These findings provide no evidence
that "action semantics" may be separated from other semantic information. Our
results support the view of a unitary semantic system, given that the
representations of action-semantic and other semantic knowledge of objects are
often simultaneously disrupted in AD.
PMID- 11011518
TI - In defense of the frontal lobe hypothesis of cognitive aging.
PMID- 11011517
TI - The frontal aging hypothesis evaluated.
AB - That the human frontal lobes are particularly vulnerable to age-related
deterioration has been frequently invoked as an explanation of functional decline
in aging. This "frontal aging hypothesis" is evaluated in this review by
examining evidence of selectively reduced frontal lobe function in aging. The
frontal aging hypothesis predicts that functions largely dependent on frontal
regions would decline in aging, while functions largely independent of frontal
lobes would remain relatively spared. The hypothesis further predicts that age
related brain change would selectively impact frontal regions. The literatures on
working memory, visuospatial attention, face recognition, and implicit memory
were reviewed as exemplars of functions dependent on prefrontal, parietal,
temporal and occipitotemporal cortices, respectively, with a view to establishing
mediating structures and effects of aging. Age sensitivity was seen both in
functions dependent on frontal integrity as well as in functions apparently
independent of frontal integrity. Further, although prefrontal areas exhibit age
related decreases in regional volume, blood flow and metabolism, nonfrontal
cortical regions undergo similar declines. It is concluded that while the frontal
lobes are subject to age-related changes reflected in both behavior and
pathology, there is only weak and conflicting evidence that frontal regions are
selectively and differentially affected by aging. It is argued that a network
based theory of cognitive aging has advantages over the localizationist approach
inherent in the frontal aging hypothesis.
PMID- 11011519
TI - Negative seizures.
AB - Negative phenomena can occur with seizures, but some ictal negative
manifestations are rare and may lead to misdiagnosis. A patient series is
presented with unusual ictal negative phenomena: neglect syndrome, catastrophic
depression, apraxia, aphasia, amnesia, homonomous hemianopsia, and hemiparesis.
One had repeated episodes with PLEDs but no parenchymal lesions. Clinicians
should consider seizures in the setting of unexplained deficits, even if there
are no positive ictal phenomena.
PMID- 11011520
TI - ECG of the month. The untamed heart. Supraventricular tachycardia, type?
PMID- 11011521
TI - Surgical management of the aging upper face.
AB - Creating a more youthful appearance of the aging upper face requires a treatment
plan which is tailored to address the patient's individual needs. The process
begins with a comprehensive knowledge of anatomy and the physical effects of
aging, involves discussion and understanding of aesthetic ideals, and culminates
in the selection and performance of the appropriate procedure.
PMID- 11011522
TI - Radiology case of the month. Incidental discovery on mammography done for a
palpable breast mass. Granular cell tumor.
AB - A 32-two-year-old woman complains of a palpable lump in her left breast. Her past
medical and family history is non-contributory. There was no palpable lump on
clinical breast examination. A mammogram was performed.
PMID- 11011523
TI - A clinical report on intravenous saline infusion in the wards of the New Orleans
Charity Hospital from June 1888 to June 1891.
PMID- 11011524
TI - The Medical Education Commission report at the turn of then new millennium 2000.
AB - The State of Louisiana Medical Education Commission was formed by Act 3 of the
1997 Louisiana Legislature. The members are appointed by the Louisiana State
University Health Sciences Center, Tulane University Medical Center, and Alton
Ochsner Medical Foundation and report to and advise the Department of Health and
Hospitals (DHH). This summation from the Medical Education Committee is designed
to answer three questions. First, how does the State of Louisiana compare
nationally in the renewal of physician supply and capability? Second, what are
the current status and trends of graduate medical education in Louisiana? Third,
what recommendations are proposed to continue and improve the important
relationship between the State public hospitals and educational programs? The
State of Louisiana has participated proportionately relative to population in the
growth and progress of medical education in this last century and compares
favorably with other states and the nation. Louisiana exceeds national averages
in the increase of primary care residency programs and positions and in the
retention of trainees in practice sites in the State. The three-year trends in
total number of graduate medical education filled positions has been consistent
with only 0.4% change, with primary care showing an overall increase of 9%,
reflecting increases in Family Medicine (56%) and Medicine/Pediatrics (41%).
PMID- 11011525
TI - Does the admissions committee select medical students in its own image?
AB - A previous issue of the Journal referred to a national study of the Myers-Briggs
Type Indicator (MBTI) in which 12 schools participated. A comparison of our
students' type preference with that of their peers at the 11 other schools
revealed that only two of the 11 schools demonstrated our strong preference for
the combination of sensing, thinking, and judging. We wondered if our Admissions
Committee members, too, would demonstrate a preference for the same combination
of Myers-Briggs dimensions. In fact, students' trait preferences matched those of
Admissions Committee members on all MBTI dichotomies, suggesting that the
Committee's own image may have influenced the selection of medical students. A
Committee member's awareness and appreciation of his own personality
characteristics may be extremely helpful in the admissions process.
PMID- 11011527
TI - Kind strangers? Physicians through the eyes of Tennessee Williams.
AB - In Louisiana, Tennessee Williams is usually thought of as a famous denizen of the
French Quarter or perhaps as our greatest playwright. Medicine rarely enters into
it. Illness, however, particularly mental illness, shaped much of Williams' life
and his work. The playwright had mixed feelings about physicians and their effect
on his life and that of his close relations. These feelings worked their way into
his plays. Through it all Williams gives a vivid, humorous, and deeply truthful
image of the doctor-patient relationship in the first half of the twentieth
century. Here we give a brief review of medicine in Williams' work.
PMID- 11011526
TI - Tuberculosis screening, referral, and treatment in an inner city homeless shelter
in Orleans parish.
AB - Tuberculosis screening and preventive therapy among the homeless has been a
challenge because of the lack of coordinated follow-up. Homeless persons at a
homeless shelter in inner city New Orleans were screened for tuberculosis
infection and referred for follow-up evaluation and preventive therapy. Fifty-two
percent of the 104 persons screened completed the initial evaluation. Twenty-two
percent of these patients had latent tuberculosis infection. Forty-two percent of
infected patients completed the referral and follow-up process. Patients during
the second 3 months of the program were twice as likely to complete the initial
evaluation, the referral, and the follow-up process as were patients during the
first 3 months due to enhanced awareness and increased educational intervention.
A competent referral system for homeless persons may be achieved by implementing
a single-clinic, on-site tuberculosis screening and follow-up system with the
active participation and coordination of state agencies, the medical community,
and organizations which operate homeless facilities.
PMID- 11011528
TI - Six degrees of Kevin Bacon--Al Eskan disease and "dirty dust.".
PMID- 11011529
TI - Lower Marine combat mortality.
PMID- 11011530
TI - Lumbar puncture headache exacerbated by recumbent position.
PMID- 11011531
TI - Vietnam nursing: the experience lives on. Interview by Margaret Ann La Salle.
AB - Through personal interviews and a review of the literature, this article examines
the experiences of three nurses who served in the Vietnam conflict. Common themes
emerging were the strength of the medical teams, the camaraderie, and the
willingness of everyone to pitch in. Common coping strategies were turning to God
for comfort and emotional support through peers.
PMID- 11011533
TI - Psychological changes of Japan Self-Defense Forces personnel during selection and
training for the peacekeeping mission in the Golan Heights.
AB - We sought to determine whether a selection process for deployment had a
measurable effect on psychological symptoms by comparing scores on the Yatabe
Guilford Personality Index, the Manifest Anxiety Scale, and the 30-item version
of the General Health Questionnaire between deployed and nondeployed mission
candidates from the Japan Self-Defense Forces. The studies were undertaken in
Japan during education and training for the United Nations peacekeeping mission
in the Golan Heights. The participants included 80 candidates for deployment.
Personnel who were not deployed had significantly higher measures of manifest
anxiety and general psychological distress than deployed personnel, whereas
deployed personnel showed more symptoms suggesting somatization. The selection
process and training for deployment appear to have been stressful for all
personnel, whether deployed or not.
PMID- 11011532
TI - Injuries and injury risk factors among men and women in U.S. Army Combat Medic
Advanced individual training.
AB - No previous reports have evaluated injuries or injury risk factors during the
advanced individual training (AIT) that follows the Army's initial or basic
combat training (BCT). This study examined injuries and injury risk factors among
439 men and 287 women participating in combat medic AIT. A questionnaire
addressing demographic and lifestyle characteristics (age, race, tobacco and
alcohol use, physical activity, etc.) was administered to all subjects. Stature
and body mass were obtained from battalion records. Injuries occurring during
both BCT and AIT were transcribed from subject medical records. Results indicated
that cumulative injury incidence (subjects with one or more injuries) in BCT was
26% for men and 52% for women (p < 0.01), in consonance with previous
investigations. In AIT, injury incidence was 24% for men and 30% for women (p =
0.08). In both BCT and AIT, overuse injuries and lower body injuries accounted
for the largest proportions of injuries by diagnosis and anatomical location.
Logistic regression revealed that older age (> 25 years), split option (a break
in service between BCT and AIT), and higher body mass were independent risk
factors for AIT injuries among women. None of the examined variables were
independent risk factors for AIT injuries among men.
PMID- 11011534
TI - Personality characteristics of South African Navy submarine personnel.
AB - This study aimed to determine the extent to which the Institute of Personality
and Ability Testing Anxiety Scale and the 16 Personality Factor Questionnaire can
be used to describe successful submariners in the South African Navy. The Anxiety
Scale scores were within normal limits when the profiles of 85 submariners were
analyzed to describe the personality characteristics of submarine personnel.
Although no significant factors were found, the results indicate that four
personality factors appeared to be most descriptive of the sample. They were
adventurousness, confidence, group orientation, and self-sentiment. These factors
appeared appropriate when discussed from an environmental demand perspective.
PMID- 11011535
TI - A field-expedient algorithmic approach to the clinical management of chemical and
biological casualties.
AB - Warriors on the modern battlefield face considerable danger from possible attack
with chemical and biological weapons. Aggravating this danger is the fact that
medical resources at the lowest echelons of care, already likely to be strained
to capacity during modern conventional combat, are at present inadequate to
handle large numbers of chemical or biological casualties. Complicating this
problem further is the austere nature of diagnostic modalities available at lower
echelons. With this in mind, and given the urgency required to adequately manage
chemical and biological casualties, it is likely that such casualties will
initially require significant empiric care in the absence of a definitive
diagnosis. Such care under field conditions, often rendered by relatively
inexperienced medical personnel, might best be provided using an algorithmic
approach. We have developed such an algorithm.
PMID- 11011536
TI - Physiological and practical evaluation of a biological/chemical protective device
for infants.
AB - The Chemical Infant Protective System (CHIPS) is a special hood-like system into
which a small battery-operated blower delivers filtered air. Because it is a
semiclosed system, there is a risk of dangerous CO2 accumulation within the
device, which particularly affects infants with acute or chronic respiratory
disorders. Eleven infants hospitalized with various respiratory illnesses wore
the device for 15 minutes. Inspired O2, inspired CO2, heart rate, respiratory
rate, oxygen saturation, and inside temperature and humidity were measured before
and during this test period. Inspired O2 and heart rate during the test period
were significantly lower than baseline levels (O2, 19.1 vs. 20.1%; heart rate,
133 vs. 142 beats/min). Inspired CO2 and inside temperature during the test
period were significantly higher than baseline levels (CO2, 0.23 vs. 0.06%;
temperature, 25.0 vs. 23.1 degrees C). Oxygen saturation, respiratory rate, and
humidity were not different from baseline levels. A short-term stay within the
CHIPS in well-ventilated surroundings did not result in significant clinical and
physiological impact for sick infants. Nevertheless, trends were identified that
may be worrisome during longer periods and in sealed rooms.
PMID- 11011537
TI - The utility of screening chest radiographs for flight physicals.
AB - Previous studies have shown low efficacy of screening chest radiographs in
various populations. Findings of approximately 3,500 screening chest radiographs
performed for flight duty were reviewed to determine the rate of detection of
significant abnormalities. There were abnormal findings in 107 chest radiographs
(3%). Fifty-five of these (1.6% of total), after additional evaluation, were
found to be false positive. Only two medically significant conditions were found
in the screening population. Based on our data, routine screening of flight duty
applicants does not appear to be justified.
PMID- 11011538
TI - Surgical implications of multicentricity in renal cell carcinoma.
AB - PURPOSE: To determine the incidence and metastatic pattern of multifocal renal
cell carcinoma in radical nephrectomy specimens and to use these findings to
guide the choice of operative procedure. MATERIALS AND METHODS: Pathology reports
for 161 patients who underwent radical nephrectomy at Walter Reed Army Medical
Center between 1980 and 1995 were reviewed to evaluate tumor size, stage, and
incidence of multifocal tumors. RESULTS: Multicentric neoplasms occurred in 16 of
161 (9.9%) radical nephrectomy specimens from the same institution. Thirteen of
the 16 multifocal tumors had cross-sectional diameters > or = 3.5 cm. Of the 16
multifocal carcinomas, 11 were noted in stage I tumors. Multifocal neoplasms were
not identified with primary tumors of < 2 cm. CONCLUSION: Our data support
previous reports that the incidence of multicentric renal malignancy is low and
suggest that patients with small, unilateral masses (< 2 cm) can undergo kidney
sparing surgery with little risk of local recurrence.
PMID- 11011539
TI - Diagnoses, demographics, and utilization of care as encountered by three U.S.
Navy general medical officers.
AB - U.S. Navy general medical officers (GMOs) are physicians serving as general
practitioners. Although exceptions exist, most GMOs are not board-certified in a
specialty. They are post-graduate year 1 (PGY-1)-trained, state-licensed
physicians analogous to civilian general practitioners. We conducted a
retrospective study using data generated from patient visits with active duty
males and females from June 1 to 30, 1998, to describe diagnoses, demographics,
and utilization of care patterns encountered by three PGY-1-trained GMOs at an
ambulatory clinic. A total of 781 patient encounters with 123 diagnoses from a
patient population of 3,178 were recorded. This is an average of 260 patient
encounters per GMO, at a rate of 2.52 patients seen per patient-care hour. Fifty
seven consultations/referrals were requested (7.3% of encounters, 1.8% of the
patient population). Personnel assigned to the clinic accounted for 4.2% of
visits (2% of the patient population). Patient satisfaction was rated as
"excellent" to "satisfactory," and no significant morbidity was observed at 1.5
year follow-up. With PGY-1 training, GMOs provide primary care to a substantial
volume of prescreened patients and treat patients with a majority of diagnoses
without referral or unacceptable complications. The role of GMOs, and perhaps
other physicians without specialty training (i.e., general practitioners), in
selected settings seems valid and may have advantageous medicoeconomic
implications for military and civilian managed care systems.
PMID- 11011540
TI - Noise attenuation of hearing protectors against heavy weapon noise.
AB - This study evaluated the noise attenuation of earplugs and earmuffs or their
combined use against heavy weapon noise in field conditions for military
personnel. The noise attenuation was measured with a miniature microphone
inserted into the ear canal. The subjects (13) were tested against pink noise and
against the noise of explosions and bazooka, mortar, cannon, and howitzer. The
attenuation (insertion loss) was 16 to 23 dB for earplugs, 10 to 20 dB for
earmuffs, and 24 to 34 dB for the combined use of plugs and muffs. The transfer
function of an open ear was 5 to 7 dB when measured as the C-weighted peak level.
The combined use of earplugs and earmuffs gave smaller attenuation values than
expected. If the limit for the C-weighted peak level is 140 dB for unprotected
ears, then protection against low-frequency noise is provided for up to 156 dB by
earplugs, up to 150 dB by earmuffs, and up to 165 dB by the combined use of plugs
and muffs.
PMID- 11011541
TI - Eye injuries in the U.S. Armed Forces.
AB - OBJECTIVE: To develop prevention and treatment modalities for eye injuries,
ophthalmologists require epidemiological data on the various types of eye
injuries. This study sought to define eye injury patterns in the U.S. armed
forces. METHOD: Data on patterns of eye injury in the armed forces were obtained
through voluntary reporting by U.S. military ophthalmologists throughout the
world. The reporting format was standardized with the U.S. Eye Injury Registry
initial and follow-up report forms. The data were analyzed for significant injury
patterns. RESULTS: Data on 112 patients were submitted, representing a broad
range of the military population. Data on a total of 96 patients with a 6-month
follow-up were analyzed in this study. Immediately after injury, 43% of the
patients were noted to have poor vision (worse than 20/200). After treatment,
only 20% were noted to have poor vision. Patients lost an average of 21.6 days of
work after a severe eye injury. CONCLUSION: An eye injury is a traumatic and
potentially debilitating event. The loss of visual acuity can be drastic,
resulting in an extensive recovery period.
PMID- 11011542
TI - Care for the Caregivers: a program for Canadian military chaplains after serving
in NATO and United Nations peacekeeping missions in the 1990s.
AB - The Mental Health Department of the Canadian Forces Support Unit (Ottawa)
developed the Care for the Caregivers program to help participants deal with
stressful events experienced directly or vicariously from the NATO and United
Nations military missions of the 1990s. The program was developed after
complaints of postdeployment stress were received from various military care
providers. The objectives were to improve the skills of support personnel and to
reduce the distress that some caregivers experienced. Thirty-one chaplains who
had been exposed to stressful military operations participated in five workshops.
These educational 4-day small-group workshops covered topics such as post
traumatic stress disorder, vicarious traumatization, coping techniques,
spirituality, self-care, and family issues. An adult education model was chosen
to encourage dialogue. Outcomes included reports of professional and personal
benefits, requests for additional programs, local education initiatives, and
referrals to mental health professionals. Having met its objectives, the program
has become a normal concluding part of stressful deployments.
PMID- 11011543
TI - A model of the expected occurrence of adverse pregnancy outcomes aboard U.S. Navy
ships.
AB - The goal of this study was to model the incidence of ectopic pregnancy and
spontaneous abortion if pregnant women in the first 20 weeks of gestation were to
remain aboard ship while at sea during deployments. Ectopic pregnancies and other
pregnancy complications at sea can be life-threatening events. Data sources
included shipboard medical departments, an Enlisted Personnel Survey, and the
Naval Health Research Center Hospitalized Pregnancy and Women Aboard Ship
studies. The overall pregnancy rate was 19 per 100 woman-years (95% confidence
interval, 18-20), based on the complement of women assigned to participating
ships. If pregnant women routinely were to remain aboard ships at sea during
deployments through their first 20 weeks of pregnancy, it is expected that
approximately 9 ectopic pregnancies and 40 spontaneous abortions would occur
aboard ships at sea.
PMID- 11011544
TI - Efficacy of 1% permethrin for the treatment of head louse infestations among
Kosovar refugees.
AB - We assessed the prevalence of head louse infestation and the effectiveness of 1%
permethrin against head lice in Kosovar refugees. A currently infested case was
defined as a person with observable crawling lice (adults or nymphs) or a person
with nits on the hair shaft within a quarter-inch of the scalp. Of the 1,051
refugees screened upon arrival in the United States, 107 (10%) were infested.
Crawling lice (adults or nymphs) were observed on 62 (6%) of the individuals
examined. Refugees with crawling lice were treated with a pediculicide containing
1% permethrin. Of these, 57 were reexamined the next day. Twenty of the 57
individuals were reexamined 7 days after treatment. No crawling lice were found
on any of the refugees examined after treatment. We conclude that 1% permethrin
treatment was effective in louse control in this refugee population.
PMID- 11011545
TI - Comparison of service member and military spouse satisfaction with installation
fitness facilities and exercise programs.
AB - Satisfaction with fitness facilities has long been accepted as a positive
contributing factor to physical activity, readiness, and overall quality of life
for military families. Our findings are based on a random sample of military
families surveyed at 38 installations worldwide and at remote locations. A total
of 8,572 service member and 3,493 spouse (55% and 32% response rate,
respectively) questionnaires were completed and returned. Overall, members were
satisfied with fitness facilities and programs, but spouses were less satisfied
and more unfamiliar with these facilities. Most valued programs were fitness
centers and swimming pools. Members reported that elimination of fitness
facilities would greatly decrease the quality of life on installations,
particularly at sites outside the continental United States, whereas spouses
reported that this would not have a dramatic effect. The results of this study
could be used to direct funding allocations, improve the health and fitness of
military families, and suggest areas for further research.
PMID- 11011546
TI - Trust, efficiency, and cooperation the heart of improving the quality of health
care in New Jersey.
PMID- 11011547
TI - HMOs still avoid meaningful patient care reform.
PMID- 11011548
TI - Senate candidates answer health care questions.
PMID- 11011549
TI - The prompt-pay law and other issues.
PMID- 11011551
TI - Anthrax. An old disease returns as a bioterrorism weapon.
PMID- 11011550
TI - With all deliberate speed: results of the first New Jersey Physician Prompt-Pay
Survey.
PMID- 11011552
TI - Avoiding the hostile work environment.
PMID- 11011553
TI - Umbilical cord blood stem cell transplantation and banking.
PMID- 11011554
TI - A provider's risk management services checklist.
PMID- 11011555
TI - A mighty task. Remarks on the swearing-in of Paul W. Armstrong as Superior Court
Judge.
PMID- 11011556
TI - The irony that follows Polly Murray's good work.
PMID- 11011557
TI - Doctor Kitzhaber/Governor Kitzhaber.
PMID- 11011558
TI - On being a scientist.
PMID- 11011559
TI - The Tao of medicine.
PMID- 11011560
TI - The Alfred Blalock centennial.
PMID- 11011561
TI - Lessons of syphilis for the age of AIDS.
PMID- 11011562
TI - Return to Aesop's fables.
PMID- 11011563
TI - Birthright.
PMID- 11011565
TI - Professionalism.
PMID- 11011566
TI - Abortion.
PMID- 11011564
TI - Audivisual memoirs of leaders in American medicine. Gertrude B. Elion, D.Sc.
(Hon.), 1918-1999.
PMID- 11011567
TI - Eavesdropping on the womb: the advent of fetal auscultation.
PMID- 11011568
TI - The quintuple threat.
PMID- 11011569
TI - "The right to die mad".
PMID- 11011570
TI - [On the necessity to use better diagnostic methods and treatment of ENT
diseases].
PMID- 11011571
TI - [Dysfunction of eustachian tube. New aspects of diagnostics and treatment].
AB - The authors review and provide a comparative assessment of diagnostic and
treatment methods in acoustic tube dysfunction. New etiopathologically sound
methods of treating long-term acoustic tube dysfunction are proposed. Therapeutic
results are analysed for 36 patients with tuber dysfunction.
PMID- 11011572
TI - [Potentials for the endonasal endoscopic surgery in the treatment of maxillary
cysts].
AB - To evaluate efficacy of endoscopic surgery in the treatment of maxillary cysts
(MC), 152 operations in 134 patients were analysed. Besides MC, 91% of the
patients had additional involvement of the nasal cavity and middle nasal passage
which required surgery. By computer tomography data, all the cysts were divided
into four groups by wall location: posteroinferior, superior, lateral, medial or
anterior. Such division is important for the choice of the surgical approach:
cysts of the first three locations can be easily removed through the middle nasal
passage, in medial and anterior cysts this approach is effective only in half the
cases. In the rest cases the sinus was opened through the anterior wall. In all,
removal of the cyst by the endonasal approach proved feasible in 73.7%, by the
anterior wall--in 26.3% of cases. The algorithm proposed for the choice of
optimal intervention implies the initial use of the external approach only in MC
located on the anterior and medial walls in the absence of concomitant lesions.
In all the other cases, surgery should begin with partial resection of the
unciform process and revision of the natural anastomosis of the sinus.
PMID- 11011573
TI - [Contemporary status of the issues in the treatment of children with respiratory
papillomatosis].
AB - For 15 years the authors treated 205 children aged 9 months to 15 years with
respiratory papillomatosis. Besides surgical endolaryngeal removal of the
papillomas, they applied immunomodulators, plasmapheresis and antiviral drugs. Of
different methods of artificial lung ventilation, the best is thought to be
transcatheter high-frequency artificial lung ventilation. As shown by the studies
of infection resistance, the combined treatment should incorporate such drugs as
zovirax and leukomax. Ultrasound disintegration and laser photodestruction with
Ho laser were introduced in surgical removal of the papillomas. The combined
treatment shortens the treatment duration and prolongs recurrence-free period.
PMID- 11011574
TI - [Assessment of the formation of interferon neutralizing antibodies and their
influence on the effectiveness of interferon therapy in children with juvenile
respiratory papillomatosis].
AB - Formation of neutralizing antibodies (NAB) to alpha-interferon (aINF) was
assessed in the reaction of antiviral activity neutralization in 36 children with
severe juvenile respiratory papillomatosis (JRP). Surgical removal of papillomas
was combined with administration of recombinant aINF preparations (reaferon,
intron A, viferon). High and moderate neutralizing activity was determined in 22
(61.1%) patients. 7, 2 and 13 of them received reaferon, intron A and viferon,
respectively. NAB were not registered in the rest 14 (38.9%) patients. The
frequency of NAB formation was not related to the preparation used, only in the
group on reaferon it was insignificantly higher. It was found that the highest
response to therapy occurred in children with low NAB titer (8 of 12 children,
66.7%), while children with high NAB titer (3 of 4 children, 75%) did not
respond.
PMID- 11011576
TI - [Aspects of nasopharyngeal microflora and middle ear function in children].
AB - Exudative otitis media (EOM) was detected in 13 (14.8%) children out of 88
preschool children at audiological investigation. In their nasopharynx, these
children carried pneumococci and hemophylic bacilli. The latter were identified
1.7 times more often in children with EOM than in those free of it. Both
pathogens were encountered in EOM children 2.6 times more frequently. It is
suggested that the above pathogens may support development and maintenance of
EOM.
PMID- 11011575
TI - [The study of aerobic bacterial background and antibiotic-sensitive isolated
strains in the ENT department].
AB - Aerobic microbes in ENT departments were studied. The following strains were
isolated: Staphylococcus, Streptococcus, Enterococcus, Acinetobacter, Klebsiella,
Pseudomonas, Flavobacter, Citrobacter, Enterobacter, Escherichia, Aspergillus,
Candida. 54.5% of the isolated strains were of hospital origin. Comparative
evaluation of antibiotic resistance has shown a wide spectrum of resistance of
the isolated microorganisms to antimicrobial drugs, among those to the drugs used
in the ENT departments.
PMID- 11011577
TI - [The evaluation of the palatine tonsil function in patients with chronic
tonsillitis].
AB - The authors review the results of the research performed in patients with chronic
tonsillitis in 1997-1999. Immunological activity of their palatine tonsils was
evaluated according to the original technique which demonstrated relations
between external functional activity of the palatine tonsils and age as well as
symptoms of chronic tonsillitis. Additional information is presented on
interrelations between lymphocytopoietic production of the palatine tonsils and
hormonal status, metabolism, ecological and physical factors. The study of
lifetime activity of the palatine tonsils is necessary for examination of local
immunity of the mucous membranes of the lymphoid pharyngeal ring.
PMID- 11011578
TI - [Vertical vestibulo-ocular interaction in unilateral labyrinth lesion
(communication II)].
AB - Vertical vestibuloocular reflex (VVOR) suppression was studied in 25 patients
with unilateral labyrinthine disorders and 22 healthy individuals. The method of
the suppression investigation was based on stimulation of the internal
semicircular channels of the labyrinth by active sagittal nodding with glance
fixation of the object moving with the head. VVOR suppression by glance reflex in
patients with unilateral labyrinthine lesion is characterized by reduced reflex
suppression effectiveness, especially on the side of the affected labyrinth, via
a significant VVOR phase shift down.
PMID- 11011579
TI - [The relationship between the condition of the brain stem compartments of the
acoustic analyzer and rheoencephalography in people who participated in the
liquidation of the consequences of the Chernobyl' nuclear plant disaster].
AB - Pure-tone and speech threshold and suprathreshold audiometry, short-latent
acoustic evoked potentials (SLAEP) and rheoencephalography (REG) were applied in
examination of 67 patients with neurosensory hypoacusis (NSH) aged 21 to 45
years. These patients worked as wreckers in the zone contaminated with
radionuclides 5 years and later after the Chernobyl accident. Relationships
between functional condition of the truncal structures of the acoustic analyser
and cerebral hemodynamics were studied. Correlation analysis has shown that there
is close correlation between SLAEP and REG, especially in the vertebrobasillar
area of cerebral circulation. The closest relations existed between the duration
of the latent period of SLAEP wave V, interpeak interval I-V and rheographic
index in the vertebrobasillar system. Combination of SLAEP and REG potentialities
opens wide prospects for revelation of the key pathogenetic links for disorders
of the acoustic system of unconventional origin, improves quality of these
disorders diagnosis, promotes individual approach to therapy of such patients.
PMID- 11011580
TI - [Otogenic cerebellar abscesses (in the light of 10-year observation materials at
the ENT clinic at the Tashkent institute of continuing education of physicians)].
AB - In 1989-1998 ENT specialists of the Tashkent Institute of Postgraduate Medical
Education treated 109 patients with otogenic intracranial complications. 13
(11.9%) of them had cerebellar abscess. Clinical symptoms of the abscesses were
obscure or absent. Head ache was the leading symptom. Other hypertensive symptoms
presented with nausea, (n = 2), vomiting (n = 5), bradycardia (n = 7). Changes on
the fundus of the eye were not registered in 6 patients. Defective coordination
of movements, scanning speech were observed in 11 and 3 patients, respectively.
Large-swinging, mixed horizontal nystagmus was truncal, in 11 patients it was
directed to the side of the abscess, in 2 patients--in both directions. Symptoms
of the secondary meningitis arose in 12 patients. The patients underwent surgical
cleaning of the middle ear and opening cerebellar abscess under drug therapy. One
patient died of purulent ventriculitis (lethality 7.6%). It is inferred that
cerebellar abscesses often run with mild symptoms. This creates diagnostic
difficulties.
PMID- 11011581
TI - [Approaches to surgical treatment of snoring and sleep apnea].
AB - Examination and treatment data on 186 patients suffering from snoring and sleep
apnea and surgical methods to manage these pathological conditions are reviewed.
The stages of the surgical treatment of snoring and sleep apnea are the
following: correction of nasal breathing, surgical intervention on the palatine
using different tools (laser, scalpel, loop, electric knife). Effectiveness of
the treatment methods, complications, postoperative developments are compared.
PMID- 11011582
TI - [Prevention and treatment of upper respiratory tract infections with IRS-19 and
polydex with phenylephrine].
PMID- 11011583
TI - [The use of controlled hypotonia in endonasal microsurgical interventions on the
paranasal sinuses in patients with chronic rhinosinusitis].
AB - The technique of controlled hypotonia was developed for adequate management of
anesthesia in endonasal microsurgical interventions on the paranasal sinuses in
patients with chronic rhinosinusitis. A total of 92 patients with chronic
polypous rhinosinusitis aged 18 to 65 years were operated using the following
variants of anesthesia: local, local in combination with neuroleptanalgesia
and/or ataralgesia with controlled hypotonia, endotracheal oxide-fluoroxene and
endotracheal oxide-oxygen anesthesias with neuroleptanalgesia and/or ataralgesia
with controlled hypotonia. This was achieved with clofelin. Controlled hypotonia
reduces blood loss in endonasal microsurgery on the paranasal sinuses in patients
with chronic polypous rhinosinusitis compared to patients unexposed to controlled
hypotonia.
PMID- 11011584
TI - [Nasonex effectiveness in allergic rhinitis and chronic polypous rhinosinusitis].
PMID- 11011585
TI - [Long-term presence of the foreign bodies in the maxillary sinuses and nasal
cavities].
PMID- 11011586
TI - [Psychogenic aphonia which has developed in a female with unilateral paresis of
the recurrent nerve].
PMID- 11011587
TI - [Current aspects of surgical treatment of Meniere's disease].
PMID- 11011588
TI - NPs and the Internet.
PMID- 11011589
TI - Easing a mother's worries.
PMID- 11011591
TI - Movin' on up.
PMID- 11011590
TI - To the test: assessment skills.
PMID- 11011592
TI - Renegotiating your salary: words for the wise.
PMID- 11011593
TI - Building bone.
PMID- 11011594
TI - Uneven ground. HIV in women of color.
PMID- 11011595
TI - On their own. School and community management of pediatric asthma.
PMID- 11011596
TI - Chronic otitis media in children. Helping families cope.
PMID- 11011597
TI - Community-acquired pneumonia. The 'captain of death' can be controlled.
PMID- 11011598
TI - Patient information. Preventing adverse drug reactions.
PMID- 11011599
TI - Alternative therapies. Tools for the new millennium.
PMID- 11011601
TI - STD issues in cyberspace.
PMID- 11011600
TI - Legal documentation. A case study in basic concepts.
PMID- 11011602
TI - Population growth--is it our concern?
PMID- 11011603
TI - Time spent in a mentor's garden.
PMID- 11011604
TI - Diagnosing irritable bowel syndrome.
PMID- 11011605
TI - Focus on fluids. Examining maternal hydration and amniotic fluid volume.
PMID- 11011606
TI - Infant abduction. Lowering the risk.
PMID- 11011608
TI - HIV and women. Understand your responsibilities; reduce your risk.
PMID- 11011607
TI - Managing second-stage labor.
PMID- 11011609
TI - Using games to enhance nursing continuing education.
PMID- 11011610
TI - Clinton signs legislation to protect breastfeeding.
PMID- 11011611
TI - Uncertified opinion. One nurse's brush with certification.
PMID- 11011612
TI - Mental health nurses must try to avoid conflict.
PMID- 11011613
TI - Is it safe for nurses to make up i.v. infusions?
PMID- 11011614
TI - Case 16: limitations of competence. Nurse who undertook a procedure outside her
competence.
PMID- 11011615
TI - Peripheral i.v. cannula dressings: advantages and disadvantages.
AB - There are many peripheral intravenous cannula dressings being used throughout the
country. This article is a review of these dressings and looks at those used in
the authors' trust as well as other products on the market. The article gives an
overview of the advantages and disadvantages of the different dressings,
including costs, that allow medical and nursing staff to make an informed choice
about the type of dressing they use. The authors felt, given all the evidence,
the traditional method of using gauze, tape or mefix was no longer acceptable
practice.
PMID- 11011616
TI - Care study: providing effective care in palliative nursing.
AB - Currently, nurses are under great pressure to demonstrate effective, evidence
based patient care. In this article a single case study will be used to
demonstrate that care can be based on recent research within a palliative care
setting to produce effective outcomes. Research-based interventions, which were
used to provide care for a patient who will be referred to as Maria, will be
discussed and evaluated to illustrate the contribution that evidence-based
practice made to her nursing care. Although it is a single case study and the
findings cannot be generalized, it is suggested that this article can be used to
demonstrate the need for accurate interpretation of assessment data, illustrate
the use of research to support nursing interventions in pain management,
constipation and skin pressure damage, and show that empirical evidence alone may
not be a sufficient basis for care and that moral issues must be taken into
account.
PMID- 11011617
TI - Safe, sound and supportive: forensic mental health services.
AB - Certain independent inquiries, the failure to implement the care programme
approach, the new mental health strategy, the recent National Service Framework
for Mental Health (Department of Health (DoH), 1999), and the Fallon Inquiry into
the Personality Disorder Unit at Ashworth Special Hospital have all raised many
questions about psychiatric care which remain unanswered. The issue of organizing
and developing forensic services can be regarded as a key element if safer
services are to be a reality. This article offers a model for forensic mental
health services which is derived from policy statements, the published strategy,
research, and discussion papers.
PMID- 11011618
TI - The development of mental health care pathways: friend or foe?
AB - Greater emphasis is being placed on mental health services to be more responsive
to clinical variation. Care pathways can standardize clinician response to
established diagnostic groups such as schizophrenia. This article discusses care
pathways using the findings of a research study carried out in London to explore
the development and implementation of a care pathway. Respondents encountered
many difficulties such as the principles behind individualized care and generic
roles and responsibilities in preformulating their work into a care pathway
sequence. This article concludes with areas for further application and research.
PMID- 11011619
TI - Evaluating expressed emotion and schizophrenia.
AB - This article presents another review from the Network for Psychiatric Nursing
Research (NPNR) National Journal Club (see Vol 8(15): 1010-12). The article
reviewed was Willets and Leff's (1997) 'Expressed emotion and schizophrenia: the
efficacy of a staff training programme'. The collated feedback comments from the
regional journal clubs is based on the format proposed by Cormack (1991). The
views expressed in this article are those of the journal club members and not
necessarily those of the NPNR.
PMID- 11011620
TI - Providing correct pressure-relieving devices for optimum outcome.
AB - Pressure redistributing (PR) support surfaces are positioned by manufacturers
against different levels of patient vulnerability to developing pressure ulcers.
However, there is no agreed method through which such linkage between a patient
and an appropriate support surface can be made. This lack of clarity leads to new
devices being positioned in a manner not representative of their eventual use in
clinical practice. Using a data hierarchy approach, three strands of evidence
(interface pressure, a pilot national survey and a randomized controlled trial)
are presented to illustrate, and support, the repositioning of the Viaclin
dynamic mattress overlay (formerly the Pegasus Overture) from use with medium
risk patients to use with higher-risk patients. The need for amendment is seen
most strikingly in the two clinical studies featured in this article, during
which 87% of all patients nursed on the Viaclin dynamic mattress overlay were at
high- to very high-risk of developing ulcers.
PMID- 11011621
TI - Transcultural competence: the challenge for nurse education.
AB - Several recent health policy directives highlight the need to overcome the health
disadvantage and discrimination experienced by many members of minority ethnic
communities. However, there is ample evidence to indicate that nurses frequently
fall short of providing sensitive and appropriate care to minority ethnic
patients. If these policy objectives are to be met, it is essential that nurse
education provides students with the opportunity to develop transcultural
competence. This article examines the current policy context before considering
the principles underpinning the development of transcultural competence. It
concludes by discussing how nurse education might more effectively prepare nurses
to meet the needs of minority ethnic communities.
PMID- 11011622
TI - Confidentiality. 11: terminal illness and the duty of confidentiality.
PMID- 11011623
TI - Wound irrigation techniques: new Steripod normal saline.
AB - Wound cleansing is performed on a regular basis by many healthcare professionals.
However, the modern concept of cleansing has not always been a priority in wound
management. There are many questions which challenge those responsible for
cleaning wounds such as how often a wound should be cleaned and which techniques
should be used. This article begins with a brief guide to wound cleansing and
then focuses on the new Steripod normal saline produced by SSL International.
PMID- 11011624
TI - General nursing does not seem to have progressed.
PMID- 11011625
TI - Year 2000. Technology of the future and rediscovering home haemodialysis.
PMID- 11011626
TI - Improving adequacy improves haemodialysis outcome.
AB - Our goal of maintenance dialysis for the coming millennium is optimal rather than
just adequate dialysis. Delivering a large amount of dialysis expressed in terms
of urea Kt/V is a necessary but insufficient measure to improve clinical outcome.
Cardiovascular morbidity and mortality remain very high in haemodialysis. This is
due in great part to the insufficient control of extra cellular volume and blood
pressure. Ours, as well as published data, indicate that up to now, only
increasing dialysis time either by prolonging the session or increasing its
frequency has proven value in overcoming this critical issue.
PMID- 11011627
TI - Review of arteriovenous fistula care.
AB - The patient with End Stage Renal Failure is largely dependent upon haemodialysis
for survival. Vascular access is the vital lifeline. This paper provides a review
of the literature and aims to advocate the advantages of arteriovenous fistulae
compared with other vascular access. It will discuss the main causes of
thrombosis in arteriovenous fistula failure, measurements of early detection of
venous stenosis and the care of an arteriovenous fistula to ensure its patency.
The responsibility of the dialysis nurse is also considered.
PMID- 11011628
TI - Influence of post haemodialysis sampling on Kt/V result.
AB - The recommended Kt/V is 1.2. Unfortunately there is no written policy for nurses
on the procedure for taking blood urea nitrogen samples post haemodialysis. The
aim of this study was to establish the Kt/V variability of haemodialysis patients
depending on the method of collection of post-haemodialysis blood urea nitrogen.
Twenty-two patients were analysed. A Kt/V was performed every 15 days during a
period of 2 months. It was taken five times on each patient: 30 minutes before
the end of a haemodialysis session (Kt/V30), at the end of haemodialysis (Kt/V1),
after slowing flows (50 ml/min) for 2 minutes (Kt/V2) and after the blood circuit
had been returned to the patient at 5 and 15 minutes respectively. (Kt/V5,
Kt/V15). The Kt/V results were: Kt/V1 1.23 +/- 0.2 Vs Kt/V2 1.14 +/- 0.19 (p <
0.003); Kt/V5- 1.05 +/- 0.19 (p < 0.002 Vs Kt/V2); Kt/V15 1 +/- 0.16 (p < 0.05 Vs
Kt/V5); Kt/V30 1.12 +/- 0.21 (pNS Vs Kt/V2). In conclusion, there was a large
variability in the Kt/V depending on the method of collection of the blood urea
nitrogen sample post-haemodialysis.
PMID- 11011629
TI - One haemodialysis unit's experience of hepatitis B.
AB - Haemodialysis patients are at high risk of contracting Hepatitis B Virus (HBV).
This blood borne virus has been responsible for many critical incidents within
haemodialysis units around the world. This paper seeks to explore one such
outbreak and at the same time look more closely at HBV and connected issues. The
incident discussed occurred within a haemodialysis unit situated in the Northwest
of England. This paper is presented as a case study. When HBV was detected in a
previously HBV negative patient a crisis management team moved quickly to contain
any possible outbreak and sought to discover the origin of the infection. An
outline of the personal and financial cost to the organisation, what lessons have
been learnt and why recommendations have been made to immunise the local dialysis
population again HBV will be presented.
PMID- 11011630
TI - Heparinisation in chronic haemodialysis treatment: bolus injection or continuous
homogeneous infusion?
AB - After several incidents where patients either bled after dialysis or suffered
severe anaphylactic reactions caused by intravenous heparin injections, we
decided to administer heparin as a continuous homogeneous intravenous infusion.
This had been usual practice in our unit in the past. Following the shocking
experience of the death of a patient due to an anaphylactic reaction during his
first dialysis, we wanted to warn colleagues for the potential dangers of
administering intravenous heparin as a bolus injection.
PMID- 11011631
TI - Experiences of patients called to hospital for a renal transplant.
AB - When patients develop end stage renal failure (ESRF) the effects can be
devastating. Patients perceive transplantation as a solution to their many
problems and it is often the treatment of choice. The aim of this study was to
examine the experiences of patients with ESRF when called to the hospital for a
renal transplant. Semi-structured interviews were taped, transcribed and a
thematic data analysis carried out. Results demonstrated that patients felt they
were given adequate support on arrival at hospital but they found the wait to
determine if they were a suitable match for the kidney difficult. There was
evidence that some patients coped with the situation by shutting out negative
possibilities.
PMID- 11011632
TI - Evaluation of potential transplant recipients and living donors.
AB - The transplant waiting list needs to be actively managed by the transplant centre
in a systematic way to achieve any degree of efficiency and effectiveness. This
paper describes the key role of the transplant nurse in a large centre with over
300 people on the transplant waiting list. It focuses on the way patients are
assessed, how the list is updated and the benefit of nurse involvement in the
work-up of potential live donors.
PMID- 11011633
TI - EDTNA/ERCA dialysis technology Journal Club. Microbiologic quality of dialysis
water.
PMID- 11011634
TI - Another choice for the blind.
AB - Automated Peritoneal Dialysis has proved to be an effective treatment for many
patients. This presentation outlines the training issues and management of a 48
year-old registered blind, insulin dependent diabetic, who developed renal
failure.
PMID- 11011635
TI - Nutritional education of CAPD patients and media influence.
AB - The aim of our paper was to investigate the short period of training offered to
peritoneal dialysis patients. We focused our attention on the nutritional
knowledge of patients who often gather information, and advice from external
factors such as their family and the media. We organized group meetings on
nutrition for 22 patients and 17 relatives. Questionnaires were completed before
and after the education programme. The group meetings improved knowledge on
nutrition and highlighted the influence of the media. The important role of the
nurse at these meetings has also been recognised.
PMID- 11011636
TI - Complications of complicated grief in renal failure.
AB - This paper sets out to bring together recurrent themes in the understanding and
care of patients with Chronic/End Stage Renal Failure centering on the key issue
of loss. A multi-disciplinary conceptual framework is proposed based on three
perspectives--Systemic, Existential and Narrative. The integrated framework for
understanding the complexity of grief issues for dialysis and pre-dialysis
patients focuses on the perception of self and the inter-relationship with others
directly involved in their care.
PMID- 11011637
TI - Quality of life and exercise in renal disease.
AB - Many publications describe the advantages of physical exercise in improving
quality of life. The aim of this study was to highlight the need for physical
activity when patients commence haemodialysis. A correlation was found between
muscular deterioration and the years on haemodialysis and it was accentuated in
men. From our study we recommend adequate physical activity at the beginning of,
and during the lifetime of haemodialysis to enhance the physical and
psychological well being of patients.
PMID- 11011638
TI - Hospice nursing--taking charge of our future.
PMID- 11011639
TI - Disease management--carpe diem home care!
PMID- 11011640
TI - Critical competencies for nurses in the new millennium.
PMID- 11011641
TI - Advanced practice nurses in home care are essential.
PMID- 11011643
TI - A home healthcare nurse's wish list: version 2000.
PMID- 11011642
TI - Behavioral health home care 2000: integration and collaboration.
PMID- 11011644
TI - Major home health regulatory changes in 2000.
PMID- 11011645
TI - Palliative care ... 2000.
PMID- 11011646
TI - Evidence-based practice for home healthcare nurses in the 21st century.
PMID- 11011647
TI - Accreditation in the new millennium.
PMID- 11011648
TI - The "R" word and the new millennium.
PMID- 11011649
TI - Challenges for home healthcare nurses in the 21st century.
PMID- 11011650
TI - Establishing a bond with clients of different cultures.
AB - In nursing, it is well known that establishing a successful nurse/client
relationship depends on the nurse's ability to promote a bond of trust between
them (Arnold & Boggs, 1995). A home care nurse working with a client from a
different culture will need to be mindful and take the extra steps mentioned in
this and other articles. Such steps will help promote this bond of trust and aid
the nurse in providing more culturally competent care. However, because every
person is unique, these same approaches and structured questions can be asked of
all patients. To do so will enable the nurse to have a more complete
understanding of each patient's health care beliefs, practices, and decision
making strategies. As has been shown through the case studies presented, gaining
a more thorough understanding of the patient and his/her family's health care
beliefs is critical to achieving cost-effective and clinically positive outcomes.
In each of the examples discussed, if these cultural assessments had not been
performed, more nursing resources and longer-term service would have been
required.
PMID- 11011651
TI - Home Talk/Healthy Talk: improving patient's health status with telephone
technology.
AB - This article describes Home Talk and Healthy Talk, two practical applications of
telephone technology developed at the VNA of Cleveland. Home Talk is a disease
specific monitoring system with preprogrammed automated questions that
immediately score patient responses. If any responses fall out of the safety
zone, the system calls the supervisor and a live intervention follows for
assessment and appropriate action. Healthy Talk is a series of age-specific
automated health screens used by nurses in community centers to engage clients to
follow through with self-selected health goals. The use, cost-effectiveness, and
impact on outcomes are also discussed.
PMID- 11011652
TI - New Joint Commission home care standards and changes for 2000.
PMID- 11011653
TI - Are you Y2K ready?
PMID- 11011654
TI - Home Care: No Boundaries.
PMID- 11011655
TI - "What a long, strange trip it's been".
PMID- 11011656
TI - Cognitive behavioural group anger management for out-patients: a retrospective
study.
AB - This study proposes that anger as the "forgotten emotion" (DiGiuseppe 1994), can
cause distress and hardship for the individual who experiences dysfunctional
anger in the form of high levels of intensity, duration and rapid onset as well
as causing distress to those who observe or are victims of the behavioural
responses to anger It is very difficult to calculate the cost of dysfunctional
anger to an individuals physical well being and relationships, or to society in
general. The author suggests the costs are immense. With this in mind anger
management training has gradually emerged in differing forms and from different
psychotherapeutic alliances. However, very little outcome data is available to
clinicians which may highlight the benefits or deficits of such programmes. To
this aim, and using Novaco's (1994) model of anger the author has attempted to
address this issue. Twenty three subjects (Ss) attended for screening assessment
six group treatment sessions and a three month follow-up session of anger
management based on Cognitive Behavioural approaches. The groups were small in
number of between 3-6 Ss. All the Ss were from the out-patient, primary care
setting, and none of them were compulsory required to attend the sessions.
Quantitative data was collected using the 1994 Novaco Anger Scale, (NAS), and
scientifically analysed. Qualitative data was collected using a semi-structured
post treatment interview, and some of the comments are discussed. The
quantitative data showed significant gains across all measures from pre to post
treatment. No gains were made during the period spent (3-6 months) on the waiting
list. The results and findings are discussed in relation to therapeutic value and
service planning.
PMID- 11011657
TI - On the importance of congruence between psychiatric staff and patient about the
patient's status.
AB - This study explores the usefulness of a method for comparing the congruence of
the staff's and the patients' perceptions of the patients' well-being. At a
psychiatric rehabilitation clinic, a comparison was made between the patients'
and the staff's views of the patients' well-being. The staff and the patients
completed questionnaires about the patients' well-being on ten occasions during a
5-year period. Through a principal components analysis of the questionnaire
scores, two conceptually similar dimensions (health-illness, and contact
distance) were identified on each set of scores. The staff and patient ratings on
the two dimensions could thus be compared. During the time of the study, a
reorganisation of the clinic was made. This made it possible to compare older and
newer units. The results indicated that the staff at long-existing units rated
the patients' health as lower than the patients did, whereas the staff at newer
units rated the patients' health as better than the patients did. The staff at
units where the patients lived in their own apartments saw the patients as less
contact-seeking than the patients did, and the staff at in-patient units saw the
patients as more contact-seeking than the patients did. The two-dimensional PC
models made it possible to visually illustrate the developments for three
individual patients. The results thus showed that the method is useful for
research purposes as well as for clinical evaluations. In the final section,
problems and assets of the method are discussed.
PMID- 11011658
TI - The milieu and milieu therapy in adolescent mental health nursing.
AB - The milieu is a well discussed concept in the mental health nursing literature;
so too is milieu therapy. Nevertheless, despite evidently clear understandings of
the milieu's significance, and of its therapeutic potential, little published
mental health nursing research focuses on these areas of practice. As a result,
within the specialty, theoretical conceptualizations of the milieu remain
unchallenged and theory development remains in its infancy. Findings from an
inquiry into the practice of adolescent mental health nursing demonstrate the:
(1) nature, (2) construction, (3) maintenance, (4) function, (5) therapeutic
effects, and (6) outcomes of the milieu. Through these findings, present
theoretical conceptualizations of the milieu are examined and expanded, and a
beginning theory of the adolescent milieu, and of milieu therapy, is presented.
PMID- 11011659
TI - Stop, look, and listen: the challenge for children with ADHD.
AB - Attention deficit-hyperactivity disorder (ADHD) is a common neuropsychiatric
disorder that appears in 4% to 13% of the U. S. population. Contrary to earlier
beliefs, ADHD frequently persists into adolescence and adulthood and is
associated with poor health choices and risk-taking behavior. Despite a vast
amount of scientific literature addressing the disorder, many misconceptions and
myths prevail creating confusion for children, their families, and health
professionals as they attempt to make treatment decisions. One new theoretical
model of ADHD shows promise in its ability to provide a more comprehensive
explanation of the disorder; it could prove useful in the development of
interventions and research programs to improve health maintenance and decrease
health-risk behavior in the ADHD population.
PMID- 11011660
TI - Problems related to the diagnosis and treatment of adolescents with leukemia.
AB - This descriptive study investigated the problems related to the diagnosis and
treatment of adolescents diagnosed with leukemia. Subjects were 8 females and 22
males diagnosed with leukemia for at least one year and who received outpatient
treatment. The study found that the information needs of the adolescents related
more to the treatment and the prognosis of the disease than to the etiology. All
subjects reported that they experienced physical problems relevant to the disease
and the treatment, and 50% reported that they experienced social problems. Also,
their social problems decreased as the time period after the diagnosis increased
and subjects were in the remission stage. Adolescents also have fears and
concerns related to the side effects of treatment and prognosis. Especially in
the recurrence stage, their fears and concerns about death are increased. Friends
and family relationships of the adolescents changed, and their future life plans
were disrupted after the disease.
PMID- 11011661
TI - Experience of teenagers born with cleft lip and/or palate and interventions of
the health nurse.
AB - The objective of this study was to describe and understand the experiences of
teenagers with cleft lip and/or palate. The human ecology approach of
Bronfenbrenner (1979) was chosen as a basis for this study. From this
perspective, the living environment of teenagers with cleft lip and/or palate was
considered, and as such, qualitative research from an ethnographic standpoint was
conducted. The data were collected by semistructured interviews and recorded on
magnetic tape. Ten teenagers, between 15 and 17 years of age, were chosen and
consulted while undergoing therapeutic treatment and surgery in a cleft lip
and/or palate clinic. The results of this study indicate that teenagers born with
this congenital malformation experience various physical, functional, or
interactional problems throughout their development. To improve this situation,
nursing care has been developed to enable the nurse to act within the
multidisciplinary team treating cleft lip and/or palate cases, thereby allowing
the teenager to develop in an environment that offers a better quality of life.
PMID- 11011662
TI - Understanding sibling adaptation to childhood cancer.
AB - Clinical research conducted over the past 40 years has described adjustment
difficulties healthy siblings face when they have a brother or sister with
childhood cancer. Research on healthy siblings of children with pediatric
malignancies has advanced over the past few years and has broadened from
distinguishing psychosocial problems following the patient's death to identifying
stressors during the illness experience. More recent research endeavors have
focused on recognizing what behaviors or interventions health care providers
understand to be most significant in promoting the patient's, parents', and
siblings' coping efforts with childhood cancer and its treatment. In addition,
descriptive research is exploring interventions used by pediatric oncology health
care providers to render social support to siblings of children with cancer
(Murray, 1999). Despite the growing body of literature on sibling adaptation to
childhood cancer, an understanding of this experience from a developmental
perspective is lacking. This lack of theoretical understanding may contribute to
inadequate care of siblings of children with cancer. Understanding the meaning
cancer has for well siblings is critical. This article discusses the theoretical
framework of child development in relation to understanding sibling adaptation to
the childhood cancer experience.
PMID- 11011663
TI - Developmental Stifling: an emerging symptom pattern.
AB - "Developmental Stifling" is a term recently developed by us to denote a symptom
pattern observed in a variety of clinical practice sites. The purpose of our
paper is to define developmental stifling and compare this recently identified
condition with Munchausen Syndrome by Proxy. A case example of developmental
stifling is provided, as well as recommendations for early identification and
treatment.
PMID- 11011664
TI - Calcium signalling mediated by the 9 acetylcholine receptor in a cochlear cell
line from the immortomouse.
AB - 1. We have investigated the characteristics of the alpha9 acetylcholine receptor
(alpha9AChR) expressed in hair cell precursors in an immortalized cell line UB/OC
2 developed from the organ of Corti of the transgenic H-2Kb-tsA58 mouse (the
Immortomouse) using both calcium imaging and whole-cell recording. 2. Ratiometric
measurements of fura-2 fluorescence revealed an increase of intracellular calcium
concentration in cells when challenged with 10 microM ACh. The calcium increase
was seen in 66 % of the cells grown at 39 degrees C in differentiated conditions.
A sm aller fraction (34%) of cells grown at 33 degrees C in proliferative con
ditions responded. 3. Caffeine (10mM) elevated cell calcium. In the ab sence of
caffeine, the majority of imaged cells responded only once to A Ch presentations.
Pretreatment with caffeine ingibited all calcium respo nses to ACh. 4. In whole
cell tight-seal recordings 10 microM ACh activa ted inward current was dependent
on the extracellular calcium concentrat ion with an estimated PCa/PNa of 80 for
the alpha9 receptor at physiological calcium levels. 5 . The data indicate that
ACh activates a calcium-permeable channel alpha 9AChR in UB/OC-2 cells and that
the channel has a significantly higher c alcium permeability than other AChRs.
The results indicate that the alp ha9AChR may be able to elevate intracellular
calcium levels in hair cell s both directly and via store release.
PMID- 11011665
TI - Pathology of femoral head collapse following transtrochanteric rotational
osteotomy for osteonecrosis.
AB - We investigated the pathology of femoral head collapse following
transtrochanteric anterior rotational osteotomy. Six femoral heads were obtained
during total hip arthroplasty some 2-12 years after osteotomy. In all cases, the
preoperatively necrotic lesions exhibited mostly osteonecrosis with accumulation
of bone marrow cell debris and trabecular bone with empty lacunae, although
repair tissue such as granulation tissue and appositional bone formation were
observed in limited areas in some cases. In the transposed intact articular
surface of the femoral head, osteoarthritic changes such as fissure penetration
to the subchondral bone and osteophyte formation were commonly observed. In newly
created subchondral areas at weight-bearing sites, trabecular thickness and the
number of trabecular bones had decreased, with few osteoblasts, osteoclasts, and
osteocytes being present, resulting in a coarse lamellar structure of the
trabecular bone. These findings suggest that transposed areas in cases of failure
consist mostly of low-turnover osteoporotic lesions which could cause collapse of
the femoral head.
PMID- 11011666
TI - Shockwave application in calcifying tendinitis of the shoulder--prediction of
outcome by imaging.
AB - This prospective study examined 62 patients (65 shoulders) with chronic courses
of calcifying tendinitis of the shoulder before and after low-energy
extracorporeal shockwave application (ESWA) in order to identify variables
associated with the outcome of this treatment. Before ESWA, radiographs and
contrast-enhanced magnetic resonance imaging (MRI) of the affected shoulders were
obtained in order to document the size and morphology of the calcifications and
the contrast media reactions in areas of interest (deposit, synovia, bursae),
respectively. In addition, a clinical evaluation was performed. After ESWA (mean
follow-up 18.2 months), clinical evaluations of all 65 shoulders revealed an
increase in the Constant score from 44% to 78% (p < 0.0001). While size (p =
0.61) and morphology (p = 0.7) of the deposits before ESWA were not associated
with the clinical outcome, negative contrast reactions around the deposits (p) =
0.0001), synovia (p = 0.0049) and bursae (p < 0.01) were associated with improved
clinical outcomes. After the total study group was divided into two groups, one
with Constant scores > or = 75% (n = 43) and the other with scores < 75% (n =
22), the positive predictive value (ppv), specificity (sp) and sensitivity (se)
were determined for the negative reaction around the deposit (ppv: 0.94; sp:
0.95; se: 0.38), synovia (ppv: 0.84; sp: 0.82; se: 0.49) and bursae (ppv: 0.86;
sp: 0.86; se: 0.44). In 5 cases (7.7%), surgery of the affected shoulder during
the follow-up period was performed. No major side-effects were seen in the study
group. In conclusion, our results suggest that in patients with chronic
calcifying tendinitis, the absence of contrast enhancement, especially around the
deposit, is a strong predictive parameter of a positive clinical outcome of ESWA.
PMID- 11011667
TI - Femoral nerve palsy in hip replacement due to pelvic cement extrusion.
AB - We report a case in which cement protrusion into the pelvis led to a major
complication. During reaming and preparation of the anterosuperior acetabulum, a
bony defect resulted which made fixation of an uncemented cup impossible, and a
cemented polyethylene cup was used instead. After surgery the patient suffered a
complete loss of femoral nerve function. Postoperative X-rays and CTs showed that
a huge mass of bone cement protruded into the pelvis in close proximity to the
iliac vessels and the femoral nerve. This probably led to nerve damage during the
cement's polymerisation process due to the heat.
PMID- 11011668
TI - Morphologic and morphometric study of patellar resurfacing with woven carbon
filamentous pads.
AB - Analysis of retrieved woven carbon filamentous pads, used for resurfacing of the
patellar joint surface, disclosed a 4-zonal organizational pattern. Zone 1,
facing the articular cavity, was devoid of carbon filaments and consisted of
fibrous tissue. Foreign body granulation tissue and fibrous tissue occupied about
one-third and approximately 50%-60% of the interfilamentous space in zones 2 and
3, respectively. Carbon filaments formed 2%-9% of zone 2 and 14%-16% of zone 3.
An interfacial membrane-like zone 4 separated the carbon filamentous pads from a
trabecular bony shell. The bone volume within the latter was approximately 25%.
Given that the purpose of articular resurfacing with implants is repopulation of
the defect by chondrocytes producing a cartilaginous matrix, the woven carbon
filamentous pads did not fulfill this expectation. In an environment of an
ongoing foreign body-induced granulomatous reaction, the stem cells permeating
the interstices of the woven carbon filamentous pad are apparently incapable of
maturing into highly differentiated cells (chondrocytes) synthesizing a highly
complex (cartilaginous) matrix.
PMID- 11011669
TI - Recurrent intrapelvic cyst complicating metal-on-metal cemented total hip
arthroplasty.
AB - Spontaneous intrapelvic masses causing vascular compression raise the suspicion
of a neoplasm or infection. We present a patient who developed a recurrent
intrapelvic cyst 14 years after a McKee-Farrar total hip arthroplasty which
presented as acute onset of lower limb swelling, threatening the vascularity of
the limb. This cyst recurred three times, and the patient finally needed revision
total hip arthroplasty. The most probable cause of the recurrence was the cement
and metal wear debris. Such cysts have been described in the literature, but to
the best of our knowledge, this is the only report that describes it complicating
a metal-on-metal prosthesis.
PMID- 11011670
TI - The epidemic of ankle fractures in the elderly--is surgical treatment warranted?
AB - Ankle fractures in the elderly are extremely common (up to 184 fractures per
100,000 persons per year, and of these approximately 20%-30% occur in the
elderly). The medical literature contains no research that has investigated ankle
fractures in the elderly. A prospective, randomised study was conducted of 84
patients with displaced ankle fractures, who were over the age of 65 years and
were assigned to operative or conservative treatment after closed reduction. The
results of treatment assessed according to the American Orthopedic Foot and Ankle
Society (AOFAS) Score showed a mean of 91.37 +/- 8.96 in the non-operated group
compared with 75.2 +/- 14.38 (P = 0.001) in the operated group. The costs of
treatment were accordingly higher. These results call for consideration of a non
operative approach to the treatment of well-reduced ankle fractures in the
elderly. Increased efforts should be invested in the prevention of these common
fractures.
PMID- 11011671
TI - Localization, detection and guided removal of soft tissue in the hands using
sonography.
AB - Penetrating wounds and lacerations are frequent pathologies treated in the
emergency room. The management of hand trauma represents a large part of the work
in any surgical practice. Although X-rays are routinely taken, numerous foreign
bodies remain undetected, and the wounds are just locally debrided and the
lacerations sutured. Unfortunately, as not all foreign bodies are radio-opaque,
the radiography results may appear normal, but the patient fails to recover.
Patients complaining of persistent wound tenderness were sent for ultrasound
investigations, and foreign bodies were detected. Had ultrasonography been
carried out initially in the emergency room, the correct diagnosis would have
been made, and the sonographic equipment could have helped to guide the physician
in his attempt to remove the foreign body. Usually, in response to continued
pain, an ultrasound investigation is ordered, and the pathology becomes apparent.
A number of examples are briefly described in order to highlight the present
inadequacies. It is suggested that hospital administrators consider the need to
provide ultrasonographic services as an integral facility of the emergency room.
PMID- 11011672
TI - Reduction of blood loss using tranexamic acid in total knee and hip
arthroplasties.
AB - There have been several attempts to reduce postoperative blood loss in patients
undergoing total arthroplasty. Benoni et al. reported the usefulness of
tranexamic acid in total knee arthroplasty (TKA). We investigated its effect in
TKA and total hip arthroplasty (THA). Blood loss was significantly reduced in
patients given tranexamic acid in both the TKA and THA groups, and no severe
complications, such as venous or pulmonary thrombosis, were noted in any of the
patients who received the agent. Administration of tranexamic acid seems to be
useful for reducing postoperative blood loss in TKA and THA.
PMID- 11011673
TI - Hyaluronan in synovial fluid of patients with loose total hip prosthesis.
Comparison with hyaluronan in patients with hip osteoarthritis and idiopathic
osteonecrosis of femoral head.
AB - The concentration and molecular weight of hyaluronan (HA) in the synovial fluid
of the hip joint were determined in 13 patients (aged 62.8 +/- 9.4 years) who had
undergone prior total hip arthroplasty(THA), 23 patients (aged 65.0 +/- 8.2
years) with osteoarthritis of the hip joint (OA), and 13 patients (aged 40.2 +/-
2.7 years) with idiopathic osteonecrosis of the femoral head (ION). A sample of
synovial fluid was obtained during revision THA because of loosening of the total
hip prosthesis for the THA group, and during the first replacement surgery or
osteotomy for the OA and ION groups. The concentration of HA in the synovial
fluid was 0.64 +/- 0.42 mg/ml in the THA group, 1.07 +/- 0.28 mg/ml in the OA
group, and 1.30 +/- 0.56 mg/ml in the ION group. The concentration of HA in the
synovial fluid of the THA patients was significantly lower than that of the OA
and ION patients (P = 0.0156 vs OA, P = 0.003 vs ION). The molecular weight of HA
was 309 +/- 88.3 x 10(4) Da in the THA group, 377 +/- 201 x 10(4) Da in the OA
group, and 240 +/- 148 x 10(4) Da in the ION group; these values do not differ
significantly (P = 0.259 vs OA, P = 0.174 vs ION). Among the THA patients, there
was no relation between the concentration of HA and the age of the patient,
length of time since the first operation, or type of prosthesis fixation; there
was also no relation between the molecular weight of HA and each of these
factors. These results suggest that a pseudosynovial membrane is regenerated
after THA, and that it produces HA of the same molecular weight as that in
patients with OA and ION, although in smaller quantities.
PMID- 11011674
TI - Posterior cruciate ligament and coupled posterolateral instability of the knee.
AB - We wanted to investigate the role of the posterior cruciate ligament (PCL) in the
knee's posterolateral stability and the magnitude of the coupled posterolateral
instability with the knee examined at 90 degrees of flexion. The coupled
posterolateral instability of the knee was studied by selective ligament cutting
in cadaver knees set at 90 degrees. The coupled posterolateral displacement after
cutting the PCL was 173% of the intact knee. With an intact PCL, the coupled
posterolateral displacement after cutting the popliteus tendon and lateral
collateral ligament with the knee at 90 degrees of flexion was 299% of the intact
knee. When the PCL was cut together with the popliteus tendon and lateral
collateral ligament, the coupled posterolateral displacement was 367%. The PCL
plays an important role in the posterolateral stability of the knee, and its
injury may cause mild (< 5 mm) to moderate (5-10 mm) posterolateral instability.
Thus, in a knee with posterolateral instability, injury of the PCL must be
considered. With an intact PCL, the posterolateral instability was very
recognizable with the knee at 90 degrees of flexion, and injury to the PCL
further increased the posterolateral instability and caused posterior translation
of the knee. Therefore, examination for posterolateral instability of the knee
should also be performed with the knee at 90 degrees of flexion, which is much
easier to perform in a clinical setting. A positive posterior translation rather
than posterolateral instability at different knee positions differentiates knees
with combined PCL and posterolateral instability from knees with isolated
posterolateral instability.
PMID- 11011675
TI - Isolated palmar dislocation of the fifth carpometacarpal joint diagnosed by
stress X-rays.
AB - Isolated palmar ulnar dislocation of the fifth carpometacarpal (CMC) joint is a
rare injury which often yields only subtle radiographic findings that may be
easily overlooked, especially when there is no associated fracture. We reported a
case of an isolated palmar dislocation of the fifth CMC joint, diagnosed
correctly by means of simple stress X-rays (traction and axial compression stress
views). This method proved to be useful and needs no special equipment.
PMID- 11011676
TI - Snapping of the proximal interphalangeal joint due to the lateral band.
AB - An unusual case is reported of snapping of the proximal interphalangeal joint
(PIPJ) of the right little finger in a 14-year-old girl. The lateral band of the
radial side slipped over the peak of the condyle of the proximal phalanx at 40
deg of flexion. The lateral band was cut and sutured to the central slip. At
follow-up examination 4 months later, there had been no recurrence.
PMID- 11011677
TI - Synovial sarcoma with a large hematoma in the inguinal region.
AB - We report the case of a patient with synovial sarcoma and a large hematoma of the
inguinal region. The patient underwent tumor resection of the lower 2/3 of the
acetabulum after preoperative chemotherapy. Twenty-four months after surgery, she
is alive without any relapse and can walk without support.
PMID- 11011678
TI - Isolated dislocation of the hamate bone. Case report and review of the
literature.
AB - A case of isolated dislocation of the hamate bone is reported. Mechanism of the
injury and treatment are described including a review of the literature.
PMID- 11011679
TI - Operative treatment of destructive spondyloarthropathy of the lumbar spine in a
patient on chronic dialysis.
AB - We present a patient with end-stage renal disease treated by chronic dialysis, in
whom progressive destructive spondyloarthropathy of the lumbar spine was
successfully managed by fusion with internal fixation, resulting in relief of
pain and restoration of activity.
PMID- 11011680
TI - Rotationplasty as a salvage procedure in revision of tumor endoprosthesis of the
distal femur--a report of two cases.
AB - We performed two rotationplasties (type A1 and A2) as salvage procedures in cases
of custom-made endoprosthetic replacements of the distal femur and knee joint.
The patients suffered from malignant bone and soft-tissue tumors of the knee,
respectively. One of them developed chronic osteomyelitis around both stems of
the prosthesis, and three local revisions turned out to be ineffective. The other
patient, suffering from parossal osteosarcoma of the distal femur, developed a
local recurrence following endoprosthetic reconstruction. The functional
abilities following the operation of these two patients suggested that
rotationplasty was a viable alternative to above-the-knee amputation in failed or
severely complicated total arthroplasty of the knee with massive bone loss.
PMID- 11011681
TI - Recurrent chondroblastoma of the upper thoracic spine. A case report and review
of the literature.
AB - A very rare case of recurrent chondroblastoma of the upper thoracic spine with a
follow-up of more than 20 years is presented and discussed with a review of the
literature.
PMID- 11011682
TI - Iris pigment epithelial cell translocation in exudative age-related macular
degeneration. A pilot study in patients.
AB - BACKGROUND: This prospective, non-controlled pilot study investigates the
practicability of IPE translocation and functional outcome in ARMD patients.
Removal of submacular choroidal neovascularization (CNV) in age-related macular
degeneration (ARMD) is usually associated with RPE damage and poor visual
prognosis. Homologous RPE transplants fail to preserve macular function, possibly
due to immune rejection. Instead of homologous RPE, we suggest translocating
autologous iris pigment epithelium (IPE), building on earlier evidence from
animal and in vitro investigations that IPE can substitute RPE functions in the
experimental animal. Immunological cell rejection is avoided. METHODS: Four eyes
with well-defined and eight eyes with ill-defined subfoveal CNV were submitted to
operation and followed up for a minimum of 6 months. IPE cells were harvested
from a peripheral iridectomy. A vitrectomy was performed. Submacular membranes
were removed, and isolated IPE cells were injected into the subretinal space.
Examinations included ETDRS visual acuity, fluorescein angiography, and SLO
microperimetry. RESULTS: All patients underwent successful surgical removal of
CNV and subretinal IPE injection. Compared to preoperative visual acuity (20/400
20/100) no significant change was observed after 6 months (20/320-16/80). A
change of more than two ETDRS chart lines was defined as significant. One eye
with preoperative ill-defined CNV developed a recurrence, leading to reduced
visual acuity. In all patients, postoperative fluorescence angiography revealed
early hyperfluorescence (window defect) in the surgically denuded area. Central
fixation was demonstrated in 50% of eyes. CONCLUSIONS: Preliminary data suggests
that IPE translocation in submacular surgery for ARMD can preserve but not
improve preoperative visual acuity over 6 months. Functional results are
promising compared to submacular membrane extraction alone and RPE
transplantation. Continued research on improvement of IPE translocation seems
justified.
PMID- 11011683
TI - Correlation among refractive, keratometric and topographic astigmatism after
myopic photorefractive keratectomy.
AB - BACKGROUND: Photorefrative keratectomy can be used to flatten the curvature of
the anterior cornea and reduce the myopic refraction of the eye. This leads to
unphysiological topographical changes of the cornea and may alter the conditions
for examinations of corneal surface topography. The purpose of this study was to
check for mutual agreement of three different methods of assessment of
astigmatism before and after myopic photorefractive keratectomy (PRK). PATIENTS
AND METHODS: Forty-seven eyes of 28 patients (age 32.7+/-6.6 years) following PRK
using an 193-nm excimer laser were included in this study. 37 eyes were treated
for pure myopia (-4.9+/-2.4 D) and 10 eyes for myopic astigmatism (sphere -2.0 to
-7.0 D, cylinder -1.0 to -3.0 D). Preoperatively and at 18 months
postoperatively, subjective refractometry, keratometry and topography analysis
were performed. The axes of topographic and keratometric cylinder were
standardized periodically (180 degrees) with respect to the refractive cylinder
axis. RESULTS: Pre- and postoperatively, the absolute astigmatism values
correlated highly significantly between all three methods (P< or =0.001). The
mean refractive cylinder was 0.65+/-0.61 D preoperatively and 0.46+/-0.41 D
postoperatively (P=0.2). The mean keratometric astigmatism was 1.14+/-0.64 D
before and 0.94+/-0.50 D after PRK treatment (P=0.2). Among the three methods,
the mean topographic astigmatism was the highest (P<0.001) preoperatively (1.31+/
0.56 D) and postoperatively (1.21+/-0.52 D) (P=0.3). In eyes treated for pure
myopia, no difference between pre- and postoperative refractive, keratometric and
topographic astigmatism was detected (P>0.5). The axes of both topographic and
keratometric astigmatism correlated highly significantly with the refractive
cylinder axis (R> or =30.9, P<0.0001). CONCLUSION: Up to 2 years after myopic
PRK, the difference between refractive and keratometric astigmatism does not
differ from the preoperative value, indicating an even corneal surface. The
absolute astigmatism values and the cylinder axis correlated well between
subjective and objective methods of astigmatism assessment. Thus, objective
measurements may be helpful in determining the cylinder component of best
spectacle correction after PRK. However, topographic analysis overestimates
astigmatism values systematically before and after PRK.
PMID- 11011685
TI - Corneal thickness and corneal endothelium in normotensive subjects with
unilateral exfoliation syndrome.
AB - PURPOSE: To examine the central corneal thickness (CCT) and corneal endothelium
in both eyes of patients with unilateral exfoliation syndrome (EXS). To determine
the effect of CCT on the measurement of intraocular pressure (IOP). METHODS: In
this cross-sectional clinical study, comparisons were made of CCT (Humphrey
Ultrasonic Pachometer), corneal endothelial cells (Keeler-Konan contact specular
microscope) and IOP (Goldmann applanation tonometer) between the exfoliative (E)
and fellow nonexfoliative (NE) eyes in 40 normotensive patients with unilateral
EXS. The CCT was used to obtain a corrected value for the IOP. RESULTS: The E
eyes had significantly higher values for CCT (0.528+/-0.030 vs 0.523+/-0.032 mm,
P<0.01) and IOP (15.7+/-3.6 vs 14.4+/-2.9 mmHg, P<0.001) than the fellow NE eyes.
The paired E and NE eyes did not differ in endothelial cell density (2779+/-540
vs 2870+/-386 cells/mm2), in the coefficient of variation of cell size (0.25+/
0.03 vs 0.26+/-0.03) or in the frequency of hexagonal cells (80.5+/-6.5 vs 82.0+/
5.0%). After correcting IOP for CCT, the E eyes still had significantly higher
IOP than the NE eyes (15.1+/-4.4 vs 14.2+/-3.7 mmHg, P<0.05). CONCLUSION:
Normotensive eyes with early EXS did not have quantitative (cell density) or
qualitative (variation in cell size, frequency of hexagonal cells) morphological
changes in corneal endothelium, but had higher values for IOP and CCT. After
correcting IOP for CCT, the E eyes still had significantly higher IOP than the
fellow NE eyes.
PMID- 11011684
TI - Optic disc vasculitis.
AB - BACKGROUND: Our studies had indicated that optic disc vasculitis (ODV) is a
distinct clinical entity. We investigated the presentation and clinical
characteristics of ODV and determined the efficacy of systemic corticosteroids in
its management. METHODS: From 1973 to 1997, we investigated 32 patients (34 eyes)
with ODV. The information was obtained by complete medical and ophthalmic history
taking and a detailed ophthalmic examination at the initial and follow-up visits.
Non-parametric analysis of demographic characteristics and Cox proportional
hazard modeling of treatment outcomes was performed. RESULTS: The most common
presenting symptom was blurred vision (in 31/34 eyes--91.2%). Visual acuity was
6/12 or better in 82.4% and 6/30 or better in 94.1% of the eyes. All eyes had an
enlarged blind spot, vitreous cells and optic disc edema. Fluorescein angiography
demonstrated retinal peripapillary phlebitis in 52.6% of the eyes. Systemic
hypertension in young patients (P=0.004) and frequency of smoking (P=0.004 for
males, P=0.046 for females) were significantly higher than in the general
population. Treatment with systemic corticosteroids improved the rate of
resolution of optic disc edema and vitreous cells, reducing median resolution
times (P=0.042). There was a tendency towards improved central visual fields with
treatment (P=0.09). Final visual acuity was 6/12 or better in 25 (92.6%) and 6/18
or better in all of the 27 eyes followed by us. CONCLUSION: Our study indicates
that our cases represent a distinct clinical entity of ODV and not just a
potpourri of unilateral optic disc edema of different etiologies. It is a self
limiting disease, usually with good prognosis, and benefits from treatment with
systemic corticosteroids. The presence of retinal peripapillary phlebitis on
fluorescein angiography suggests mild vasculitis of the optic nerve head as the
primary pathological mechanism in this disorder.
PMID- 11011686
TI - Counterrotation of the globe in macular translocation.
AB - BACKGROUND: Macular translocation is a new treatment option in age-related
maculopathy. The aim of this study was to report experience with the handling of
the sensory problems concerning subjective cyclorotation and binocularity that
arise with this technique. METHODS: The data of 33 patients who had undergone
macular translocation and counterrotation of the globe by muscle surgery in a
first operation, followed by silicone oil removal and sometimes revision of the
eye muscles in a second operation, were evaluated. The counterrotation consisted
of a partial transposition of the rectus muscles and extensive surgery on the
anterior margins of the oblique eye muscles. Subjective monocular cyclorotation,
motility and binocularity were tested. RESULTS: In 5 patients after the two
operations binocular single vision was proved; in one of these cases there was
even stereoscopic function. Seventeen patients excluded one eye: 13 excluded the
operated eye, 4 the fellow eye. Eleven patients experienced double vision or
tilted images under binocular viewing conditions and thus required further
surgery or occlusion of one eye. CONCLUSION: The majority of patients were not
hindered by subjective cyclorotation. Nevertheless, in a large proportion of
patients binocularity could not be reestablished because of still reduced visual
acuity or cyclotropia. The data show that the aim of restoring binocularity can
be achieved but in practice is often not attained.
PMID- 11011687
TI - Measurement of a novel optic disc topographic parameter, "spikiness", in
glaucoma.
AB - BACKGROUND: Structural changes in the lamina cribrosa have been implicated in the
pathogenesis of glaucomatous optic atrophy, but not observed. This paper presents
a novel parameter of topographic variability within the optic disc, termed
"spikiness", which may reflect glaucoma-related changes in the lamina. METHODS:
Four age-matched groups of normal patients (n=12, mean age 64.8 years) and
patients with ocular hypertension (n=14, mean age 63.1), primary open-angle
glaucoma (n=11, mean age 70) and low-tension glaucoma (n=15, mean age 66.3) were
recruited. Images of normal and glaucomatous eyes from the Heidelberg Retina
Tomograph were imported into ERDAS image processing software where the spikiness
data (30 consecutive mean surface height values across the base of the optic cup
in both the vertical and horizontal meridians) were extracted in a format that
facilitated further statistical analysis. RESULTS: Significant differences in
topographic variability (spikiness) existed in the vertical (F=3.64, P=0.01) but
not the horizontal meridian (F=1.25, P=0.3) through the optic disc. Spikiness was
inversely related to Humphrey mean deviation (P<0.05), and cup-disc ratio
(P<0.004) and was directly related to nerve fibre layer thickness (P<0.005). Of
particular interest was the finding that the spikiness measure was the only optic
disc parameter to significantly discriminate low tension glaucoma from primary
open angle glaucoma. CONCLUSION: A new measure of surface variability
(topography) at the floor of the optic cup has been described. The new index of
spikiness may represent a measurement of lamina cribrosa fragility which has been
implicated, but not previously estimated, in glaucomatous eyes.
PMID- 11011688
TI - Long-term results of pneumatic retinopexy.
AB - PURPOSE: To evaluate the long-term outcome (>6 years) of retinal reattachment by
pneumatic retinopexy. METHODS: Seventy-eight eyes were examined retrospectively
after treatment of a retinal detachment with pneumatic retinopexy. The average
follow-up period was 6.35 years. The fundus was examined and visual acuity was
documented and compared to that of the fellow eye. Any reoperations were
evaluated. RESULTS: In 98.7% of cases permanent reattachment of the retina was
achieved. In 85.9% the primary intervention had been successful. However, the
retina redetached in 19.4% of these during the first 3 months and in a further
4.5% later during the observation period, requiring reoperation. The average
number of operations necessary to obtain permanent reattachment of the retina in
the 77 eyes was 1.39. One eye was lost due to phthisis bulbi and had to be
enucleated. Six years after the first intervention visual acuity of the eyes
without reoperation was 0.57 (+/-0.25 SD) with initially detached macula [fellow
eye 0.67 (+/-0.27)] and 0.7 (+/-0.27) with attached macula [fellow eye 0.7 (+/
0.25)]. Visual acuity of the eyes with reoperation was 0.36 (+/-0.3) [fellow eye
0.51 (+/-0.29)] with initially detached macula and 0.64 (+/-0.26) [fellow eye
0.63 (+/-0.35)] with attached macula. CONCLUSION: Six years after initial
pneumatic retinopexy the retina was found to be attached in 98.7% of eyes. In
65.4% this result had been achieved by minimally invasive primary surgery alone.
The need for reoperation was evident during the first 3 months in 89% of the
cases. The final visual outcome was satisfactory overall.
PMID- 11011689
TI - Cellular migration into neural retina following implantation of melanin granules
in the subretinal space.
AB - BACKGROUND: In some retinal diseases and following transplantation of retinal
pigment epithelium (RPE), melanin granules are liberated to the subretinal space.
Our aim was to investigate the cellular response to implanted extracellular
melanin. METHODS: After pars plana vitrectomy, 17 albino rabbits received a
suspension of melanin granules in the subretinal space. Postoperative examination
included ophthalmoscopy, color fundus photography, histology using monoclonal
antibodies identifying RPE cells (AE1/3), macrophages (RAM 11), B-lymphocytes
(CD20) and T-lymphocytes (CD45), and electron microscopy. The follow-up time was
2 weeks, 4 weeks and 6 months. RESULTS: On fundus photographs, the layer of
melanin showed focal attenuation with lighter areas at 6 months. Melanin granules
were phagocytosed by RPE cells and macrophages at 2 weeks, as identified by
monoclonal antibodies. In areas where an abundance of melanin was present,
multilayers of macrophages were seen associated with considerable photoreceptor
damage. Pigment-laden cells invaded the neural retina. The cellular infiltration
of the retina was focal, and when it involved the outer nuclear layer the
photoreceptor damage was severe. Electron microscopy demonstrated the presence of
melanosomes intracellularly in Muller glia. The process of phagocytosis and
removal of melanin granules from the subretinal space was slow and not completed
at 6 months. CONCLUSION: Our experiments show that implantation of melanin
granules in the subretinal space of albino rabbits may induce a considerable
phagocytic cellular response featuring the host's RPE, macrophages and glial
cells. The migration of pigment-laden cells into the neural retina was associated
with focal photoreceptor damage.
PMID- 11011690
TI - Morphological changes of retinal pigment epithelial and glial cells at the site
of experimental retinal holes.
AB - PURPOSE: To investigate morphological changes of retinal pigment epithelial (RPE)
cells and glial cells in the immediate and early phases of restoration at the
site of experimental retinal holes. METHODS: We made 0.2-disc-diameter retinal
holes with a vitreous cutter in albino rabbit eyes. To assess very early changes
of RPE cells, the eyes were enucleated at 0,1,3, and 5 h postoperatively and
observed by scanning electron microscopy (SEM). At 1,5, and 7 days after surgery,
eyes were enucleated and prepared in thin and ultra-thin sections for observation
by light and transmission electron microscopy (TEM). RESULTS: SEM showed the
surface of the RPE cells lifting a few hours after surgery at the site of the
retinal holes. The tissue filling the retinal hole was amorphous and homogeneous,
as viewed by light microscopy. TEM revealed that this tissue consisted of glial
cell processes containing many organelles. In addition, the cytoplasm of the
cells was relatively dark, while the surface of the filling tissue continued
smoothly to the internal limiting membrane. These findings suggested that these
cell processes were parts of Muller cells. CONCLUSION: RPE cells and glial cells
assembling at the site of the retinal hole may play an important role in retinal
hole closure in this experimental model. In addition, RPE cells were
morphologically changed in an immediate phase of restoration.
PMID- 11011691
TI - Inhibition of lens epithelial cell proliferation by substituted PMMA intraocular
lenses.
AB - BACKGROUND: Migration and proliferation of lens epithelial cells (LECs) are based
on interactions between cellular integrins and extracellular matrix proteins
(ECMs). We were able to design polymers substituted with COO- and SO3- groups
that counteract LEC proliferation through modification of the integrin/ECM
interaction. The objective of this study was to compare the cell proliferation
inhibiting properties of differently substituted copolymers with those of a
homopolymer. METHODS: Polymers were synthesized by radical polymerization and
characterized by nuclear resonance spectroscopy. Second-passage rabbit LECs were
cultured either on PMMA homopolymers (control) or on substituted PMMA copolymers.
Cells were counted on days 2, 7, and 17. Cell vitality was evaluated by trypan
blue staining. Experiments were run in quadruplicate. Statistical analysis was
performed using the Wilcoxon test and the Mann-Whitney U-test. RESULTS: Compared
with control, cells cultured on copolymers grew to significantly lower cell
numbers. The inhibitory effect became evident at day 2 after seeding and
persisted throughout the experiment. Different ratios of COO-/SO3- substitutions
yielded different grades of inhibition. No toxic effect was seen on rabbit LECs.
CONCLUSIONS: The tested copolymers inhibit cell proliferation and are nontoxic.
Further evaluation could lead to the development of new intraocular lens
materials that prevent secondary cataract.
PMID- 11011692
TI - Ballistic transfer of minimalistic immunologically defined expression constructs
for IL4 and CTLA4 into the corneal epithelium in mice after orthotopic corneal
allograft transplantation.
AB - BACKGROUND: Experiments were performed to determine whether corneal epithelium
transfected with minimalistic immunologically defined expression constructs for
the extracellular fragment of CTLA4 and for interleukin-4 (IL-4) or interleukin
10 (IL-10) is able to modulate an allospecific immune response after orthotopic
corneal grafting in mice. METHODS: Six groups of BALB/c (H-2d) mice received a
C3H (H-2k) corneal graft and dexamethasone eye drops until day 11. Five groups of
BALB/c mice had gold particles delivered into the corneal epithelium by Gene Gun
on day 10 after transplantation. In four groups, minimalistic immunologically
defined gene expression (MIDGE) vectors were delivered into the corneal
epithelium by ballistic transfer. The levels of expressed IL-4 and IL-10 were
determined by an enzyme-linked immunosorbent assay (ELISA) in shock-frozen
homogenized corneas. The expression kinetics of Gene-Gun-transfected corneas were
determined by measuring luciferase in lysed whole corneas at different time
intervals. RESULTS: Luciferase expression was detectable during the first 5 days
following transfection. ELISA was used to determine IL-4 and IL-10 expression in
corneal tissue 36 h after transfection. Ballistic IL-4 and CTLA4 gene transfer
significantly prolonged corneal graft survival in comparison with the gold
treated control group and the IL-10-treated group. CONCLUSION: The beneficial
effect of IL-4 and CTLA4, but not IL-10 gene transfer into the corneal epithelium
by MIDGE vectors was demonstrated for the first time in corneal transplantation.
PMID- 11011693
TI - Ex vivo canine lens capsular sac explants.
AB - BACKGROUND: Lens capsular sac explants from human cadaver eyes were used to
investigate posterior capsular opacification (PCO). The purpose of this study was
to characterize a similar model using canine tissue and to determine whether
transferrin (Tf), transforming growth factor beta-2 (TGF-beta2), and insulin-like
growth factor-1 (IGF-1) are secreted by lens epithelial cells (LEC) of these ex
vivo sacs. METHODS: The lens from canine eyes was removed by extracapsular
cataract extraction, the lens sac dissected free, pinned to a petri dish, and
cultured in either serum-supplemented or serum-free medium. Morphologic
characteristics and growth rate to confluence on the posterior capsule were
studied by phase-contrast microscopy. Vimentin, alpha smooth muscle actin, and
panTGF-beta expression by LEC were determined by immunohistochemistry. Tf, TGF
beta2, and IGF-1 levels were measured by ELISA in the supernatant of sacs
cultured in serum-free medium. RESULTS: The mean time to confluence of LEC onto
the posterior capsule was 5.4+/-1.1 days (n=22) and 14.7+/-3.7 days (n=14) for
sacs in serum-supplemented and serum-free medium, respectively. Following
development of confluence, explants displayed opacification and light scatter
from cellular proliferation and capsular contraction. Confluent LEC expressed
vimentin, alpha smooth muscle actin, and TGF-beta2, and both Tf and TGF-beta2
were secreted into the culture supernatant. CONCLUSION: Canine lens sac explants
have characteristics virtually identical to those of human origin, and appear to
be a useful alternative tissue source for this model when human cadaver eyes are
unavailable. Tf and TGFbeta-2, but not IGF-1, are secreted by LEC in explanted
lens sacs and may influence the proliferation and metaplasia of LEC during the
development of PCO.
PMID- 11011694
TI - Maculo-papillary branch retinal artery occlusions following the Wada test.
AB - BACKGROUND: The Wada test induces short-term anesthesia of one hemisphere by
injection of sodium amytal into an internal carotid artery. It is an important
presurgical diagnostic tool in epileptic patients. PATIENT: A 22-year-old man
with idiopathic epilepsy noticed a shadow in the central visual field of his
right eye immediately following a Wada test of the right hemisphere. RESULTS: The
patient presented with an occlusion of two small branch retinal arteries and
corresponding defects in his visual field. Fluorescence angiography revealed
small dense hyperfluorescent spots within the occluded retinal vessels.
CONCLUSION: Branch retinal artery occlusions are a possible complication of the
Wada test, possibly induced by undissolved contrast medium or sodium amytal.
PMID- 11011695
TI - Molecular dynamics estimates of ion diffusion in model hydrophobic and KcsA
potassium channels.
AB - Molecular dynamics simulations are carried out to obtain estimates of diffusion
coefficients of biologically important Na+, K+, Ca2+ and Cl- ions in hydrophobic
cylindrical channels with varying radii and large reservoirs. Calculations for
the cylindrical channels are compared to those for the KcsA potassium channel,
for which the protein structure has recently been determined from X-ray
diffraction experiments. Our results show that ion diffusion is maintained at
reasonably high levels even within narrow channels, and does not support the very
small diffusion coefficients used in some continuum models in order to fit
experimental data. The present estimates of ion diffusion coefficients are useful
in the calculation of channel conductance using the Poisson-Nernst-Planck theory,
or Brownian dynamics.
PMID- 11011696
TI - Effect of Adriamycin on the boundary lipid structure of cytochrome c oxidase:
pico-second time-resolved fluorescence depolarization studies.
AB - The fluorescence dynamics of the dye 3,3'-diethyloxadicarbocyanine iodide (DODCI)
was used to probe the microenvironment of cytochrome c oxidase (CcO) and
cardiolipin. The dye was partitioned between an aqueous and a hydrophobic phase.
The 'bound' and 'free' populations of DODCI could be separated by analysis of the
time-resolved fluorescence decay of the dye. The anisotropy decay of the DODCI
bound to CcO showed a unique 'dip and rise' shape that was analyzed by a
combination of rotational correlation times with time-dependent weight factors
for each lifetime component. Rotational dynamics studies revealed the existence
of a restricted motion of the dye bound at the enzyme surface. Adriamycin, an
anticancer, albeit cardiotoxic drug, was previously proposed to affect the
surface structure of CcO, most likely by causing a disorder to the surface lipid
arrangement. A drastic change in the rotational correlation time of the dye bound
to the enzyme surface was observed, which suggested a depletion of cardiolipin
layer due to complexation with the drug. The effect of Adriamycin on cardiolipin
was drastic, leading to its phase separation. The present study suggests that the
effect of Adriamycin on CcO is primarily a segregation of the cardiolipins.
PMID- 11011697
TI - Phospholipid monolayer of plant lipid bodies attacked by phospholipase A2 shows
80 nm holes analyzed by atomic force microscopy.
AB - In plant storage tissue, lipid bodies are composed of triacylglycerides and
surrounded by a phospholipid monolayer which is stabilized by oleosins. At the
onset of lipid body mobilization, cells express phospholipase A2, which partially
degrades the monolayer and thus provides access for the subsequently acting
triacylglyceride degrading enzymes. Analyzing the lipid body surface by atomic
force microscopy we show that, at the stage of maximal phospholipase A2
expression, the monolayer contains holes of approximately 80 nm in width and 2.45
+/- 0.46 nm in depth. Non-contact mode imaging was performed with a lateral
resolution of approximately 10 nm and a vertical resolution of less than 0.1 nm.
The depth of the holes corresponds to the width of the monolayer, while the width
of the channels is sufficiently large to provide access to 100 kDa enzymes, such
as lipoxygenase and lipases.
PMID- 11011699
TI - A new outlook on the energetics of muscle contraction.
AB - Analysis of experimental data on two muscles demonstrates that, in contracting
striated muscle, the total rate of ATP splitting, nu(t) (number of ATP molecules
split per active myosin head per second), comprises of three separate components:
nu(p), which is required for the generation of the contractile force P which is
equal to the external load; nu(v) which is devoted to the development of the
velocity of shortening V; and nu(w), which is responsible for the production of
the mechanical power (PV). Nu(p) is proportional to P and nu(v) to V, which means
that the sliding distance is independent of P. The mechanical power was found to
be equal to the free energy change associated with the hydrolysis of nu(w), which
means that the thermodynamic efficiency of the power-producing component is
practically 100%. It is concluded that ATP hydrolysis is actually three different
reactions. The analysis leads to Hill's force-velocity relationship. Its
empirical constants a and b are expressed by thermodynamic and molecular
parameters. The constant a was found to be inversely proportional to the sliding
distance. The same considerations and conclusions should apply also to other
muscles and to the movement under load of microtubules interacting with, e.g.
kinesin.
PMID- 11011698
TI - DNA, RNA and hybrid RNA-DNA oligomers of identical sequence: structural and
dynamic differences.
AB - A 27-mer sequence was synthesised as DNA duplex (DD), RNA duplex (RR), and RNA
DNA (RD) hybrid in order to characterise their structural and dynamic features.
The hydrodynamic radius (Rh) and the rise (b) values of the three samples were
consistent with the conformations predicted by CD analysis. The value of the
torsional constant (alpha) of the samples containing RNA was approximately twice
that of the DD sample and followed the order: DD < RD < RR. The same order was
observed in the thermodynamic stability and in the reduction of the
electrophoretic mobility. gamma-Ray footprinting analysis was carried out to
resolve the individual strand conformation in the hybrid. The RNA strand
preserved its conformation, while the DNA strand showed local deformations mainly
at TA and TG steps.
PMID- 11011700
TI - Analysis of potentiometric titrations of heterogeneous natural polyelectrolytes
in terms of counterion condensation theory: application to humic acid.
AB - A model, developed within the framework of the counterion condensation theory of
linear polyelectrolytes, is presented in this paper to describe the acid-base
properties of linear polyelectrolytes, consisting of several types of functional
ionizable groups. This formalism has been successfully applied to Fluka humic
acid under salt-free conditions, as well as in the presence of supporting simple
1:1 salt (KNO3) at three different concentrations. As part of this approach, the
charge density of the humic acid is obtained from the activity coefficient
measurements of potassium counterions at different humic acid concentrations at a
constant degree of dissociation of the polyelectrolyte. The humic acid average
charge density was found to be 0.80 +/- 0.05. Using the present model, we are
able to satisfactorily describe the experimental data obtained from acid-base
potentiometric titrations. Four main functional groups making up the polymer are
determined through their fractional abundances (Xi) and intrinsic pK (pK0i)
values. The fractional abundances remained constant and independent of the ionic
strength, indicating that the humic acid constitution does not depend on the
concentration of excess salts. The pK0i values show a small change with ionic
strength, which can be explained by the polyelectrolytic behavior of the
solution.
PMID- 11011701
TI - Effect of temperature on viscosity properties of some alpha-amino acids in
aqueous urea solutions.
AB - Viscosities for solutions of glycine, DL-alpha-alanine, DL-alpha-amino-n-butyric
acid, DL-valine, DL-leucine and L-serine in 5 mol kg(-1) aqueous urea have been
determined at 278.15, 288.15, 298.15 and 308.15 K. The viscosity B-coefficients
for the amino acids in the aqueous urea solution have been calculated at
different temperatures. The effect of temperature on the B-coefficients is
discussed on the basis of the Feakins equation. The contribution of solute to the
activation parameters (delta mu0*2, deltaH0*2, deltaS0*2) for viscous flow of the
solution have been calculated, together with the Gibbs energy, enthalpy and
entropy of transfer for the amino acids from the ground-state solvent to the
hypothetical viscous transition state solvent. The contributions of the charged
end group (NH3+, COO-) and CH2 groups of the amino acids to B-coefficient and
delta mu0*2 have been also estimated using the linear correlations between B
coefficient or delta mu0*2 and the number of carbon atoms in the alkyl chains of
the amino acids. All the activation parameters are discussed in terms of the
solute-solvent interactions in the ground and transition states.
PMID- 11011702
TI - Relating helix tilt in a bilayer to lipid disorder: a mean-field theory.
AB - We present a mean-field theory relating the helix tilt angle in a bilayer to
lipid disorder. The theory provides a method to compare the rotational barriers
for different helices in lipid bilayers. The results suggest that the helix tilt
angle is strongly affected by both the hydrophobicity of the helix and the
average lipid disorder. This leads us to point out future experiments that could
shed light on lipid-protein interactions.
PMID- 11011703
TI - A thermodynamical study of the clockwork hypothesis proposed by E. Schrodinger.
AB - In the present study, the 'clockwork' hypothesis proposed by Schrodinger was
examined from the viewpoint of thermodynamics. Firstly, noticing a unidirectional
transfer of entropy in a heat engine, the logic was briefly explained about a
close relation between this entropy transfer and an irreversible cycle performed
by a working body. Next, paying attention to two fundamental differences between
a heat engine and a biological system, we considered an isolated system Asigma
consisting of three one-component systems (Ai, A, Ao) and noted a case that the
same molecules as the component ones flowed quasistatically into Ai from the
outside. Then, the unidirectional flows of the molecules, energy and entropy,
which were induced by the above inflow in Asigma, were formulated on the basis of
the equilibrium thermodynamics for an open system. Furthermore, it was clarified
that the fundamental equation for these flows is the Schrodinger inequality and
that the necessary-sufficient condition for this inequality is the existence of
an irreversible cycle performed by A. Here A corresponds to a working body in a
heat engine. It was, thus, concluded that the 'clockwork' hypothesis by
Schrodinger is considered to be reasonable for a biological system composed of
various irreversible subsystems.
PMID- 11011704
TI - Transpupillary thermotherapy for age-related macular degeneration: long-pulse
photocoagulation, apoptosis, and heat shock proteins.
AB - OBJECTIVE: To provide a biophysical foundation for using transpupillary
thermotherapy (TTT) to manage choroidal neovascularization in age-related macular
degeneration (ARMD). METHODS: Retinal temperature rise in laser therapy is
proportional to retinal irradiance (laser power/area) for a particular spot size,
exposure duration, and wavelength. TTT is a low irradiance, large spot size,
prolonged exposure (long-pulse), infrared laser photocoagulation protocol.
Results from an experimentally confirmed, finite element model of retinal light
absorption and heat conduction are used to analyze laser parameter selection and
its consequences. Results from apoptosis, heat shock protein and hyperthermia
research are used to examine how chorioretinal damage from clinical procedures
might be reduced. RESULTS: Chorioretinal thermal equilibration occurs during long
pulse TTT photocoagulation. Retinal temperature increases are similar in the RPE
where laser radiation absorption is significant and in the adjacent neural retina
where there is negligible radiation absorption. For parameters used to treat
occult choroidal neovascularization in lightly-pigmented fundi (800-mW, 810-nm, 3
mm retinal spot diameter, 60-sec exposure duration), the maximum chorioretinal
temperature elevation is calculated to be roughly 10 degrees C, significantly
lower than the 20 degrees C temperature elevations measured in threshold,
conventional short-pulse retinal photocoagulation. CONCLUSIONS: To achieve a
preselected temperature rise, TTT laser power must be increased or decreased in
proportion to the diameter rather than the area of the laser spot. Clinical power
settings should be adjusted for fundus pigmentation and media clarity because
both of these factors affect absorbed retinal irradiance and thus retinal
temperature rise. Noninvasive thermal dosimetry currently is unavailable for
clinical retinal photocoagulation, but potential thermometric techniques include
MRI, liposomal-encapsulated dyes, multispectral imaging or reflectometry, and
subretinal or episcleral thermometry. TTT may be useful not only as independent
therapy, but also as an adjunct to PDT, antiangiogenic drugs and ionizing
radiation therapy in the management of neovascular ARMD. Low temperature, long
pulse photocoagulation is a potential strategy for decreasing neural retinal
damage in subsequent TTT or short-pulse photocoagulation and perhaps even for
treating glaucoma or retinal degenerations.
PMID- 11011705
TI - Scleral buckling for stage 4 retinopathy of prematurity.
AB - BACKGROUND AND OBJECTIVE: Both vitrectomy and scleral buckling have been used to
treat patients with stage 4 retinopathy of prematurity (ROP). The standard
procedure of scleral buckling for treatment of stage 4 ROP is encircling scleral
buckling. The effectiveness of segmental scleral buckling is still unclear. The
purpose of this study was to analyze the surgical results of patients with stage
4 retinopathy of prematurity treated with either encircling or segmental scleral
buckling. PATIENTS AND METHODS: We retrospectively analyzed the anatomic outcomes
of 23 eyes (18 infants) with stage 4 A or B ROP treated with scleral buckling.
Segmental buckling was used to treat 15 eyes with detachment limited to the
temporal side of the retina, while 9 eyes with detachment involving both the
nasal and temporal sides were treated with encircling scleral buckling. RESULTS:
Macular reattachment during a mean follow-up period of 34 months (range: 2 weeks
to 9 years) was accomplished in 11 (79%) of the 14 eyes treated with segmental
scleral buckling and 4 (44%) of the 9 eyes that received encircling scleral
buckling. There were no intraoperative complications recorded. None of the eyes
that achieved macular reattachment developed recurrent macular detachment during
the follow-up period. CONCLUSIONS: Scleral buckling appears to be effective for
treatment of stage 4 ROP. In patients with temporal side retinal detachment only,
segmental scleral buckling provides adequate treatment for stage 4 ROP.
PMID- 11011706
TI - Visual field results after vitreous surgery in a case series of patients with
open-angle glaucoma.
AB - BACKGROUND AND OBJECTIVE: Visual field loss is a complication of vitrectomy and a
concern for patients with glaucoma. Our objective was to determine whether
vitrectomy is associated with new field defects in patients with glaucoma.
PATIENTS AND METHODS: This retrospective case series involved 7 eyes of 7
patients, who had open-angle glaucoma and underwent vitrectomy for macular hole
(2) or epiretinal membrane (5). RESULTS: Acuity improved by at least two lines in
5 eyes. Visual fields showed a change in mean deviation following vitrectomy
(mean difference -1.50 dB, P=0.0006, paired Student's t-test). One eye had
confirmed progression of a pre-existing visual field defect, but no new defects
were apparent in the other eyes. Transient intraocular pressure rises requiring
therapy occurred in 3 eyes. One eye developed macular edema, but no other
operative complications occurred. CONCLUSIONS: The results of our small case
series suggest that vitrectomy may be an acceptable intervention in eyes with
glaucoma and co-existing macular problems.
PMID- 11011707
TI - Pars plana vitrectomy for macular holes combined with cataract extraction and
lens implantation.
AB - BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of cataract
extraction and lens implantation at the time of pars plana vitrectomy (PPV) for
macular hole (MH) repair. MATERIALS AND METHODS: A retrospective study was
conducted of 21 eyes that had PPV for MH combined with cataract extraction and
lens implantation. Visual acuities (VA) were followed and complications noted.
RESULTS: Of 21 eyes, successful anatomic closure was achieved in 16 (76.2%), and
13 (62.0%) improved in VA by at least 2 Snellen lines. Few complications
occurred. CONCLUSION: Procedures that combine PPV for MH with cataract extraction
and lens implantation decrease the need for future ophthalmic surgery, allow for
clearer intraoperative visualization, and facilitate visual rehabilitation. This
combined procedure is a relatively safe and effective alternative to separate
pars plana and cataract surgeries.
PMID- 11011708
TI - One-year follow-up of laser trabeculoplasty using Q-switched frequency-doubled
Nd:YAG laser of 523 nm wavelength.
AB - BACKGROUND AND OBJECTIVE: To investigate clinical efficacy and safety of a new
laser treatment of open angle glaucoma that targets pigmented cells in the
trabecular meshwork for disruption. MATERIALS AND METHODS: The 16 eyes of chronic
open angle glaucoma patients were treated in the method similar to argon laser
trabeculoplasty using Q-switched, frequency-doubled Nd:YAG laser (523 nm). The
treatment results were followed and analyzed for a one-year period. RESULTS: Mean
intraocular pressure reduction of 3.81 mm Hg (15%) at 3 months, 3.94 mm Hg
(16.1%) at 6 months, and 4.93 mm Hg (20.2%) at 12 months from the baseline were
obtained. Slightly greater reductions were seen in the responder group that
consisted of eyes showing 3 mm Hg or greater reduction. Adverse reactions were
minimal and not significant. CONCLUSION: This new laser trabeculoplasty has shown
reasonable efficacy and safety on a limited number of eyes over a one year
duration.
PMID- 11011709
TI - Prospective randomized comparison of simultaneous and sequential bilateral
photorefractive keratectomy for the correction of myopia.
AB - BACKGROUND AND OBJECTIVE: To evaluate the efficacy and safety of simultaneous
bilateral photorefractive keratectomy (PRK). PATIENTS AND METHODS: There were 52
patients (104 eyes) with myopia less than -6 diopters entered in this prospective
trial and randomized to simultaneous or sequential bilateral PRK. Main outcome
measures were uncorrected visual acuity (UCVA), percentage of eyes within +/-0.5
D of attempted outcome, present pain intensity (PPI) and total pain rating index
(PRI(R)T) scores resulting from McGill the Pain Questionnaire, subjective
symptoms, haze, and patient satisfaction. Follow-up extended to 14 months.
RESULTS: There was no significant difference in UCVA (P=0.996) and percentage of
eyes within +/-0.5 D of attempted correction (P=0.932). Present pain intensity
and PRI(R)T scores were significantly higher in the sequential group (P=0.037;
P=0.034). The percentage of satisfied patients after bilateral PRK was
significantly higher in the simultaneous group (P=0.036). CONCLUSIONS:
Simultaneous bilateral PRK was safe and effective, without any significant
difference from sequential treatment.
PMID- 11011710
TI - Corneal endothelial damage after neodymium:YAG laser iridotomy.
AB - BACKGROUND AND OBJECTIVE: This study examined the long-term effect of
neodynium:YAG (Nd:YAG) laser iridotomy on the corneal endothelium. PATIENTS AND
METHODS: A prospective study was designed. Patients with narrow and occludable
angles or fellow eye of acute angle closure glaucoma attack were treated with
Nd:YAG laser iridotomy. For one year, 31 eyes of 21 patients underwent complete
follow-up. Corneal endothelial specular microscopy was performed before and after
laser iridotomy at 1, 3, 6, and 12 months. RESULTS: The decrease of endothelial
cell density after YAG laser iridotomy was statistically significant at 1 month
(P = 0.036), 6 months (P = 0.004), and 12 months (P = 0.000), respectively. The
decrease was not statistically significant at 3 months (P = 0.467). Linear
regression analysis indicated no statistical correlation between the percentage
change in endothelial cell density and the total energy used during the treatment
(1 month: P=0.08, 3 months: P= 0.3, 6 months: P=0.9, 12 months: P=0.2).
CONCLUSION: This study demonstrated significant endothelial cell loss in the 1
year follow-up. The result suggested that Nd:YAG laser iridotomy may pose a long
term hazard to the corneal endothelium.
PMID- 11011711
TI - Exophiala werneckii endophthalmitis following cartaract surgery in an
immunocompetent individual.
AB - A case of infectious endophthalmitis caused by the saprophyte Exophiala werneckii
is reported. This has not been recognized as a pathogen for ocular infections
previously. The infection followed uncomplicated cataract surgery involving
phacoemulsification and IOL implant. Clinical presentation was that of an
indolent endophthalmitis with relatively acute onset. Pars plana vitrectomy,
fungal stains, and culture established the diagnosis. Initial management
consisted of empirical intravitreal injection of vancomycin, ceftazidime, and
amphotericin B. Treatment was supplemented with a 3-week course of systemic
fluconazole and topical therapy with natamycin, atropine, ciprofloxacin, and
diclofenac. The visual acuity returned to 20/20-2 with no recurrence of
infection. The source of the infection could not be determined. Fungal
endophthalmitis has to be considered as a rare, though important, complication
following ophthalmic surgery. Specific fungal stains and cultures are helpful for
establishing the diagnosis early in the course of disease. E werneckii should be
considered in the differential diagnosis of fungal endophthalmitis.
PMID- 11011712
TI - Combined hamartoma of the retina and retinal pigment epithelium with full
thickness retinal hole and without retinoschisis.
AB - Combined hamartoma of the retina and retinal pigment epithelium has been
described as a rare, benign tumor formed by an overgrowth of several constituents
of the retina such as the retinal pigment epithelial cells, vascular elements,
and glial components.1 Despite its varied clinical appearance it is important to
recognize this tumor as it is known to simulate intraocular malignancies like
retinoblastoma and choroidal melanoma.
PMID- 11011713
TI - Pre-Descemet's hematoma in a patient of congenital glaucoma with Descemet's
detachment: a unique form of hemorrhage.
AB - A unique form of anterior segment hemorrhage called Pre-Descemet's hematoma is a
previously unreported type of hemorrhage in which blood collects in the narrow
space between the corneal stroma and detached Descemet's membrane, which in our
case was because of congenital glaucoma associated with Haab's straie.
PMID- 11011714
TI - Phacoemulsification and opaque intraocular lens implantation for the treatment of
intractable diplopia.
AB - Intractable diplopia secondary to paralytic strabismus may be treated with the
occlusion of the affected eye. Established treatments include occlusion with a
patch, opaque spectacles or contact lenses, and performing upper lid lowering
procedures or tarsorrhaphies. Two cases are presented in which intractable
diplopia was resolved by performing clear lens phacoemulsification and the
insertion of an opaque intraocular lens. Both patients reported a resolution of
their diplopia having been dissatisfied with other forms of treatment. Although
opaque intraocular lens insertion is not recommended as the initial treatment of
choice in such cases, it offers a valuable treatment option for those patients in
whom other forms of therapy have failed.
PMID- 11011715
TI - CO2-laser in the removal of a plexiform neurofibroma from the eyelid.
AB - We present a child with neurofibromatosis type I (NF-I) who underwent excision of
a large upper lid neurofibroma using a CO2-laser. Plexiform neurofibromas are
notorious for their bleeding tendency and the inability to achieve complete
surgical excision. The CO2-laser is an adjunct to achieving better hemostasis and
delineation of the tissue in the absence of natural tissue planes caused by the
tumor's diffuse mode of growth. Using the CO2-laser achieves better cosmesis,
while reducing operation time and limiting complications.
PMID- 11011716
TI - Epithelial folds following slippage of LASIK flap.
AB - We present a case of a slipped corneal flap after laser-assisted in-situ
keratomileusis, LASIK. A 22-year-old, female with myopia and a refractive error
of -5.50 D sph OU had an uneventful LASIK performed on her left eye with a Chiron
Automated Corneal Shaper (ACS) and a VISX-Star Excimer laser using a nasal hinged
flap. On the first postoperative day, slit lamp examination revealed 4.0 mm
slippage of the corneal flap. The flap was rolled and folded on itself within the
inferior cul-de-sac. With the aid of the operating microscope, the flap was
repositioned on the stromal bed. Immediately following the repositioning, many
folds were still visible despite centering the flap on the stromal bed and
performing stretching maneuvers. Detailed examination showed the folds to be of
edematous epithelial origin. The underlying stromal bed was flat. Within days
following repositioning, the folds had disappeared and the flap assumed the
typical postoperative LASIK appearance. The final uncorrected visual acuity
returned to 20/20.
PMID- 11011717
TI - Repairing the hole in hydroxyapatite orbital implants following peg removal.
AB - Pegging hydroxyapatite implants may lead to improved prosthetic eye movement but
may also be associated with complications that may occasionally require peg
removal. Removing the peg and leaving the peg hole to spontaneously granulate in,
is one technique to deal with the remaining implant hole. The author describes a
simple technique to fill the peg hole that provides a smooth implant-conjunctival
prosthesis interface and may potentially allow repegging.
PMID- 11011718
TI - Bilateral retinoschisis, retinal neovascularization, and severe myopia in a young
female.
PMID- 11011719
TI - Performance of capillary columns for high-temperature gas chromatography
AB - The developments in stationary-phase synthesis and capillary column technology
have opened new perspectives in the analysis of high-molecular-weight compounds
(600 daltons) and thermolabile organic compounds by high-temperature-high
resolution gas chromatography. This branch of high-resolution gas chromatography
deals with analysis performed up to 390 degrees C oven temperature (with some
applications going up to 420 degrees C and even a few applications to 450 degrees
C maximum). The technique has been applied to many different fields of science
(e.g., organic geochemistry, environmental chemistry, archeology, and natural
product research). Apolar and medium-polar gum phases can now be operated at
temperatures from 400 to 480 degrees C, but these higher temperatures are seldom
used because of the thermostability of the material used to make the capillary
tubing. This paper shows the performance of nine commercial high-temperature
columns when used in routine applications.
PMID- 11011720
TI - Measurement of gas-liquid partition coefficient and headspace concentration
profiles of perfume materials by solid-phase microextraction and capillary gas
chromatography-mass spectrometry
AB - An empirical model describing the relationship between the partition coefficients
(K) of perfume materials in the solid-phase microextraction (SPME) fiber
stationary phase and the Linearly Temperature Programmed Retention Index (LTPRI)
is obtained. This is established using a mixture of eleven selected fragrance
materials spiked in mineral oil at different concentration levels to simulate
liquid laundry detergent matrices. Headspace concentrations of the materials are
measured using both static headspace and SPME-gas chromatography analysis. The
empirical model is tested by measuring the K values for fourteen perfume
materials experimentally. Three of the calculated K values are within 2-19% of
the measured K value, and the other eleven calculated K values are within 22-59%.
This range of deviation is understandable because a diverse mixture was used to
cover most chemical functionalities in order to make the model generally
applicable. Better prediction accuracy is expected when a model is established
using a specific category of compounds, such as hydrocarbons or aromatics. The
use of this method to estimate distribution constants of fragrance materials in
liquid matrices is demonstrated. The headspace SPME using the established
relationship between the gas-liquid partition coefficient and the LTPRI is
applied to measure the headspace concentration of fragrances. It is demonstrated
that this approach can be used to monitor the headspace perfume profiles over
consumer laundry and cleaning products. This method can provide high sample
throughput, reproducibility, simplicity, and accuracy for many applications for
screening major fragrance materials over consumer products. The approach
demonstrated here can be used to translate headspace SPME results into true
static headspace concentration profiles. This translation is critical for
obtaining the gas-phase composition by correcting for the inherent differential
partitioning of analytes into the fiber stationary phase.
PMID- 11011721
TI - High-performance liquid chromatographic determination of glycogen in sea urchin
gonads with refractive index detection.
AB - A high-performance liquid chromatographic method using refractive index detection
for the determination of glycogen in sea urchin (Paracentrotus lividus) gonads is
developed. After alkaline digestion with sodium carbonate, samples are adjusted
to pH 4.6 with citric acid and incubated with amyloglucosidase to hydrolyze the
glycogen. The resulting glucose is determined using a Spherisorb NH2 column as
the stationary phase and an acetonitrile-water mixture (80:20, v/v) as the mobile
phase. The relative standard deviation (%) was 3.57, the limit of detection was
40.1 microg/mL, and the recovery percentage was 97.2%.
PMID- 11011722
TI - Computer simulation for the simultaneous optimization of any two variables and
any chromatographic procedure.
AB - Computer software that allows the simulation of any chromatographic separation as
a function of simultaneous changes in any one or two variables that can affect
sample separation order (selectivity) is described. For one example, an
application is described for the simultaneous variation of the mobile phase pH
and gradient time in reversed-phase liquid chromatography. The accuracy of such
predictions is examined for a sample mixture of 17 substituted benzoic acids and
anilines, and requirements for an acceptable predictive accuracy are summarized.
In a second example, the separation of three peptides by capillary
electrophoresis is optimized.
PMID- 11011723
TI - Quantitation of a metal deactivator additive by derivatization and gas
chromatography--mass spectrometry
AB - The quantitative analysis of phenolic and amine-containing petroleum additives
can be challenging. One such compound-N,N'-disalicylidene-1,2-propanediamine, a
common metal deactivator additive (MDA)--is thought to inhibit fuel oxidation
catalyzed by metals both in the fuel and on surfaces. The ability to measure the
concentration of MDA in storage stability tests, thermal-stressing studies, and
field samples is important. Quantitating low concentrations of MDA can be
difficult because of surface adsorptivity due to the phenol and amine functional
groups. This paper describes the shortcomings of direct-injection gas
chromatography-mass spectrometry to quantitate MDA as well as a solution to the
analytical problem using the common silylation agent BSA to derivatize the MDA.
Results demonstrate that the silylation technique is suitable for the
determination of MDA concentrations in aviation fuel samples and suggests that
the MDA may be readily determined in other petroleum products with a lower
detection limit for MDA of 0.5 mg/L. Measurements conducted in heated batch
reactors indicate that MDA concentration is reduced as hydrocarbon fuels are
stressed. In addition, only free or available MDA is measured by this technique,
not MDA that is complexed with metals.
PMID- 11011724
TI - Extraction of atrazine and its metabolites using supercritical fluids and
enhanced-fluidity liquids
AB - Supercritical fluid and enhanced-fluidity liquid extractions are performed on
spiked sediment samples containing atrazine (ATRA) and five of its metabolites
including desisopropyldesethylatrazine, desethylhydroxyatrazine (DEHA),
desisopropylatrazine, desethylatrazine, and hydroxyatrazine (HA). The
hydroxylated metabolites are of particular interest because of their increased
water solubility and the fact that their high polarity makes them difficult to
analyze. Soxhlet extractions using methanol are conducted for the purpose of
comparison. Results of the extractions show that the hydroxy-containing
metabolites of ATRA are not effectively extracted with supercritical CO2 alone.
The solvating or desorbing power of carbon dioxide appears too low to extract HA
and DEHA. The extraction recoveries of the hydroxylated metabolites increase when
enhanced-fluidity liquid mixtures of methanol/CO2 are used, and these rates
increase with the methanol concentration. Enhanced-fluidity ternary liquid
mixtures of H2O/methanol/CO2 yield the best recoveries for these compounds. ATRA
recoveries are equally effective when using supercritical CO2 or enhanced
fluidity mixtures. The other nonhydroxy-containing metabolites require the
increased solvent strength of either large percentages of methanol in CO2 or
ternary mixtures of H2O, methanol, and CO2 for high recoveries. Recoveries with
enhanced-fluidity liquid ternary mixtures are better than the recoveries from
Soxhlet for all the compounds in the study.
PMID- 11011726
TI - How can I clean my column having an alkyl amine IP reagent?
PMID- 11011725
TI - Chromatographic properties of the ion-exclusion column IonPac ICE-AS6 and its
application in environmental analysis, Part II: application in environmental
analysis
AB - Biological processes, geochemical reactions, anthropogenic emissions, and
transformation reactions of xenobiotics are responsible for the widespread
occurrence of aliphatic carboxylic acids in the environment. To study the
performance of the ion-exclusion chromatography column IonPac ICE-AS6 in the
analysis of environmental and environmental-technical samples, organic acids are
investigated in composting seepage, silage effluents, aqueous extracts of sewage
sludge, molasses hydrolysate, and alkaline cellulose hydrolysates. With respect
to the diverse sample matrix and composition, different chromatographic
conditions are applied. It is possible to determine various volatile fatty acids,
dicarboxylic acids, (poly)hydroxy acids, and keto acids as main and trace
components in samples with very high and low dissolved organic carbon content.
Low baseline noise allows the determination of malic and succinic acid in the
concentration range of approximately 1 microM/L in the presence of higher
concentrations of fully ionized compounds. The applicability of the column in
environmental analysis may be limited by the poor retardation of strong organic
acids, insufficient separation of some relevant substance combinations (i.e.,
citric and isocitric acid), and very strong hydrophobic interactions with
straight-chain monocarboxylic acids containing four or more carbon atoms.
PMID- 11011727
TI - An occupancy factor of unity should always be used for waiting rooms and other
highly-occupied public areas.
PMID- 11011728
TI - X-ray videodensitometric methods for blood flow and velocity measurement: a
critical review of literature.
AB - Blood flow rate and velocity are important parameters for the study of vascular
systems, and for the diagnosis, monitoring and evaluation of treatment of cerebro
and cardiovascular disease. For rapid imaging of cerebral and cardiac blood
vessels, digital x-ray subtraction angiography has numerous advantages over other
modalities. Roentgen-videodensitometric techniques measure blood flow and
velocity from changes of contrast material density in x-ray angiograms. Many
roentgen-videodensitometric flow measurement methods can also be applied to CT,
MR and rotational angiography images. Hence, roentgen-videodensitometric blood
flow and velocity measurement from digital x-ray angiograms represents an
important research topic. This work contains a critical review and bibliography
surveying current and old developments in the field. We present an extensive
survey of English-language publications on the subject and a classification of
published algorithms. We also present descriptions and critical reviews of these
algorithms. The algorithms are reviewed with requirements imposed by neuro- and
cardiovascular clinical environments in mind.
PMID- 11011729
TI - Localization of cerebral arterovenous malformations using digital angiography.
AB - Since 1989 we performed stereotactic radiotherapy treatments of cerebral
arterovenous malformations (AVM), estimating three-dimensional (3-D) localization
and shape of target volumes by the Leksell stereotactic helmet on two orthogonal
radiographic projections. Due to the limitations of this method, we developed a
new technique for the localization of the target volume using digital subtraction
angiography (DSA) and digital image processing. To achieve this result we first
developed a method to correct nonlinear distortion of DSA images using spatial
relocation of image pixels based on a calibration grid. We then developed an
algorithm for localization of the target volume using two independent DSA
projections. Target volume coordinates in the helmet system are calculated using
two DSA acquisitions taken with a free angle (approximately 90 degrees), one in
the AP and the other in the LL direction. The helmet can be freely positioned
between the x-ray source and the image plane. The projections of eight reference
points inserted in the helmet at a known location, are used to calculate the
transformation matrix between the two coordinate systems. We performed numerical
and experimental validation of the system. A hypothetical random error (up to 2
mm) on image coordinates of the reference points allowed to determine that the
error in target localization was less than 0.2 mm. Using DSA images of target
points with a known location within a phantom, the error between calculated and
actual location was, on average, 0.30+/-0.13 mm (mean+/-SD), with a maximum error
of 0.49 mm. The results of numerical and experimental validations show that the
system we have developed allows fast and accurate localization of the center of
the target volume and it is suitable for efficient guiding during stereotactic
radiosurgery of AVM.
PMID- 11011730
TI - Fast reconstruction with uniform noise properties in halfscan computed
tomography.
AB - The hybrid algorithms developed recently for the reconstruction of fan-beam
images possess computational and noise properties superior to those of the fan
beam filtered backprojection (FFBP) algorithm. However, the hybrid algorithms
cannot be applied directly to a halfscan fan-beam sinogram because they require
knowledge of a fullscan fan-beam sinogram. In this work, we developed halfscan
hybrid algorithms for image reconstruction in halfscan computed tomography (CT).
Numerical evaluation indicates that the proposed halfscan-hybrid algorithms are
computationally more efficient than are the widely used halfscan-FFBP algorithms.
Also, the results of quantitative studies demonstrated clearly that the noise
levels in images reconstructed by use of the halfscan-hybrid algorithm are
generally lower and spatially more uniform than are those in images reconstructed
by use of the halfscan-FFBP algorithm. Such reduced and uniform image noise
levels may be translated into improvement of the accuracy and precision of lesion
detection and parameter estimation in noisy CT images without increasing the
radiation dose to the patient. Therefore, the halfscan-hybrid algorithms may have
significant implication for image reconstruction in conventional and helical CT.
PMID- 11011731
TI - Quantitative in vivo analysis of the kinematics of carpal bones from three
dimensional CT images using a deformable surface model and a three-dimensional
matching technique.
AB - The purpose of this study was to obtain quantitative information of the relative
displacements and rotations of the carpal bones during movement of the wrist.
Axial helical CT scans were made of the wrists of 11 volunteers. The wrists were
imaged in the neutral position with a conventional CT technique, and in 15-20
other postures (flexion-extension, radial-ulnar deviation) with a low-dose
technique. A segmentation of the carpal bones was obtained by applying a
deformable surface model to the regular-dose scan. Next, each carpal bone, the
radius, and ulna in this scan was registered with the corresponding bone in each
low-dose scan using a three-dimensional matching technique. A detailed definition
of the surfaces of the carpal bones was obtained from the regular-dose scans. The
low-dose scans provided sufficient information to obtain an accurate match of
each carpal bone with its counterpart in the regular-dose scan. Accurate
estimates of the relative positions and orientations of the carpal bones during
flexion and deviation were obtained. This quantification will be especially
useful when monitoring changes in kinematics before and after operative
interventions, like mini-arthrodeses. This technique can also be applied in the
quantification of the movement of other bones in the body (e.g., ankle and
cortical spine).
PMID- 11011732
TI - Evaluation of an algorithm for the assessment of the MTF using an edge method.
AB - An algorithm to calculate the presampling modulation transfer function (MTF) of
an imaging system from an angled edge image has its own inherent transfer
function. Factors such as the angle of the sampling aperture to the edge,
registration of edge function profiles using the determined edge angle,
differentiation, smoothing, and folding all combine to produce the frequency
response of the algorithm. In this work, the profile registration transfer
function accounting for an error in the determined edge angle has been derived.
This has been incorporated with other, previously reported, algorithm component
transfer functions to fully characterize the MTF calculation algorithm. When
registering profiles, small errors in the edge angle determination were found to
result in large errors in the MTF, as the misalignment errors increase with the
number of profiles. For example, registering 50 profiles a 0.07 degree error in a
7 degree edge angle (1% error) produces a 36% error in the MTF at the system
cutoff frequency f=f(c) when profiles are oversampled at a frequency
f(s)=8f(c)(f(c) is defined as the maximum frequency reproducible without aliasing
when sampling at the limiting system Nyquist frequency f(s) = 2f(c)). These
results highlight the importance of quantifying the transfer function of the
algorithm used to determine an imaging system modulation transfer function. The
MTF calculation algorithm and the transfer function analysis have been
incorporated into a Windows-based software program to be made available for
general use.
PMID- 11011733
TI - Analytic reconstruction of magnetic resonance imaging signal obtained from a
periodic encoding field.
AB - We have proposed a two-dimensional PERiodic-Linear (PERL) magnetic encoding field
geometry B(x,y) = g(y)y cos(q(x)x) and a magnetic resonance imaging pulse
sequence which incorporates two fields to image a two-dimensional spin density: a
standard linear gradient in the x dimension, and the PERL field. Because of its
periodicity, the PERL field produces a signal where the phase of the two
dimensions is functionally different. The x dimension is encoded linearly, but
the y dimension appears as the argument of a sinusoidal phase term. Thus, the
time-domain signal and image spin density are not related by a two-dimensional
Fourier transform. They are related by a one-dimensional Fourier transform in the
x dimension and a new Bessel function integral transform (the PERL transform) in
the y dimension. The inverse of the PERL transform provides a reconstruction
algorithm for the y dimension of the spin density from the signal space. To date,
the inverse transform has been computed numerically by a Bessel function
expansion over its basis functions. This numerical solution used a finite sum to
approximate an infinite summation and thus introduced a truncation error. This
work analytically determines the basis functions for the PERL transform and
incorporates them into the reconstruction algorithm. The improved algorithm is
demonstrated by (1) direct comparison between the numerically and analytically
computed basis functions, and (2) reconstruction of a known spin density. The new
solution for the basis functions also lends proof of the system function for the
PERL transform under specific conditions.
PMID- 11011734
TI - Simultaneous iterative reconstruction for emission and attenuation images in
positron emission tomography.
AB - The quality of the attenuation correction strongly influences the outcome of the
reconstructed emission scan in positron emission tomography. Usually the
attenuation correction factors are calculated from the transmission and blank
scan and thereafter applied during the reconstruction on the emission data.
However, this is not an optimal treatment of the available data, because the
emission data themselves contain additional information about attenuation: The
optimal treatment must use this information for the determination of the
attenuation correction factors. Therefore, our purpose is to investigate a
simultaneous emission and attenuation image reconstruction using a maximum
likelihood estimator, which takes the attenuation information in the emission
data into account. The total maximum likelihood function for emission and
transmission is used to derive a one-dimensional Newton-like algorithm for the
calculation of the emission and attenuation image. Log-likelihood convergence,
mean differences, and the mean of squared differences for the emission image and
the attenuation correction factors of a mathematical thorax phantom were
determined and compared. As a result we obtain images improved with respect to
log likelihood in all cases and with respect to our figures of merit in most
cases. We conclude that the simultaneous reconstruction can improve the
performance of image reconstruction.
PMID- 11011735
TI - Partial wave analysis of the ultrasound comet tail artifact.
AB - An adaptation of linear acoustic scattering theory is used to describe the comet
tail artifact which is observed in the diagnostic ultrasound imaging of small
spherical masses. The calculated backscattered pressure wave is shown to
correspond well with the appearance of the artifact in a variety of clinical
images.
PMID- 11011736
TI - Application of coloring theory to reduce intensity modulated radiotherapy dose
calculations.
AB - Coloring theory is applied to reduce the dose calculations under intensity
modulated radiotherapy. Intensity modulated radiotherapy varies the intensity
profile across the beam. The beam face is divided into a panel of small squares
or "bixels." Each square may be opened or closed for different lengths of time by
moving collimator leaves in and out of the beam. It has been shown that the
distribution of dose from radiation directed through any open square depends on
whether the adjacent squares are opened or closed. Taking the states of
neighboring bixels into account greatly increases the required dose calculations.
There are 2(8) possible ways to select open or closed states for the eight
neighbors of a given bixel. Each combination represents one coloring of a 3 x 3
panel, and each coloring demands a separate dose calculation. The number of
calculations is reduced by considering the symmetries of a square. The 256
possible colorings can be divided into 51 distinct patterns through application
of Burnside's theorem. Each pattern consists of selections of closed bixels that
are the same except for a symmetric transformation of coordinates. If the
symmetry between x and y coordinates is broken by collimator leaves whose ends
and sides have different effects on bordering bixels, the number of patterns
increases to 84. The theoretic gain in the number of calculations through the
application of Burnside's theorem is fivefold if bixel borders are symmetric, and
threefold if the borders are asymmetric. The results are applied to examples of
generated intensity maps. The symmetry rules divide the bixel arrangements into
proportionately fewer patterns as the intensity maps become larger, allowing
computational gains to be achieved.
PMID- 11011737
TI - Computer verification of fluence map for intensity modulated radiation therapy.
AB - In a treatment planning system for intensity modulated radiation therapy (IMRT),
the time sequence of multileaf collimator (MLC) settings are derived from an
optimal fluence map as a postoptimization process using a software module called
a "leaf sequencer." The dosimetric accuracy of the dynamic delivery depends on
the functionality of the module and it is important to verify independently the
correctness of the leaf sequences for each field of a patient treatment. This
verification is unique to the IMRT treatment and has been done using radiographic
film, electronic portal imaging device (EPID) or electronic imaging system (BIS).
The measurement tests both the leaf sequencer and the dynamic multileaf
collimator (MLC) delivery system, providing a reliable assurance of clinical IMRT
treatment. However, this process is labor intensive and time consuming. In this
paper, we propose to separate quality assurance (QA) of the leaf sequencer from
the dynamic MLC delivery system. We describe a simple computer algorithm for the
verification of the leaf sequences. The software reads in the leaf sequences and
simulates the motion of the MLC leaves. The generated fluence map is then
compared quantitatively with the reference map from the treatment planning
system. A set of pre-defined QA indices is introduced to measure the "closeness"
between the computed and the reference maps. The approach has been used to
validate the CORVUS (NOMOS Co., Sewickley, PA) treatment plans. The results
indicate that the proposed approach is robust and suitable to support the complex
IMRT QA process.
PMID- 11011738
TI - An optimized forward-planning technique for intensity modulated radiation
therapy.
AB - Intensity modulated radiation therapy (IMRT) has stirred considerable excitement
in the radiation oncology community. Its objective is to make the dose conform to
the tumor and spare other organs. Instead of resorting to the rather complex
inverse-planning, the technique described here is an extension of the
conventional treatment planning technique. The beam orientation and wedge angles
are chosen in the conventional rule-based manner. However, within each conformal
beam's eye view (BEV) field including margin, a number of sub-field openings are
added. The smaller field openings are designed to irradiate the tumor, while
sparing the normal tissue of the organs at risk (OARs) that intrude into the
target region in the BEV. As the number of intrusions into the target BEV
increases, the number of sub-fields for each beam increases. The Cimmino
simultaneous projection method was employed to obtain the optimized weighting for
each field of each beam. In cases where the dose constraints for the tumor and
for the OARs are reasonable, it is possible to obtain a plan with a fairly small
number of beams that satisfies the specified dose objectives. This is illustrated
for the treatment of prostate cancer, where the rectum creates a concavity in the
planning target volume. An advantage of this technique is that the quality
assurance for the delivery of these plans does not require extensive special
efforts.
PMID- 11011739
TI - Estimating the dose variation in a volume of interest with explicit consideration
of patient geometric variation.
AB - A method to measure the effects of internal organ motion and deformation and
patient setup error on cumulative dose variation in a volume of interest is
proposed. The method uses multiple CT scans and electronic portal images of a
single patient to numerically simulate dose-volume effects over the entire course
of the patient's external beam treatment. The results are expressed in the form
of a novel dose-volume histogram, called an expected dose-volume histogram
(EDVH).
PMID- 11011740
TI - A two-step algorithm for predicting portal dose images in arbitrary detectors.
AB - Recently, portal imaging systems have been successfully demonstrated in
dosimetric treatment verification applications, where measured and predicted
images are quantitatively compared. To advance this approach to dosimetric
verification, a two-step model which predicts dose deposition in arbitrary portal
image detectors is presented. The algorithm requires patient CT data, source
detector distance, and knowledge of the incident beam fluence. The first step
predicts the fluence entering a portal imaging detector located behind the
patient. Primary fluence is obtained through ray-tracing techniques, while
scatter fluence prediction requires a library of Monte Carlo-generated scatter
fluence kernels. These kernels allow prediction of basic radiation transport
parameters characterizing the scattered photons, including fluence and mean
energy. The second step of the algorithm involves a superposition of Monte Carlo
generated pencil beam kernels, describing dose deposition in a specific detector,
with the predicted incident fluence. This process is performed separately for
primary and scatter fluence, and yields a predicted dose image. A small but
noticeable improvement in prediction is obtained by explicitly modeling the off
axis energy spectrum softening due to the flattening filter. The algorithm is
tested on a slab phantom and a simple lung phantom (6 MV). Furthermore, an
anthropomorphic phantom is utilized for a simulated lung treatment (6 MV), and
simulated pelvis treatment (23 MV). Data were collected over a range of air gaps
(10-80 cm). Detectors incorporating both low and high atomic number buildup are
used to measure portal image profiles. Agreement between predicted and measured
portal dose is better than 3% in areas of low dose gradient (<30%/cm) for all
phantoms, air gaps, beam energies, and detector configurations tested here. It is
concluded that this portal dose prediction algorithm is fast, accurate, allows
separation of primary and scatter dose, and can model arbitrary detectors.
PMID- 11011741
TI - Dependence of the tray transmission factor on collimator setting and source
surface distance.
AB - When blocks are placed on a tray in megavoltage x-ray beams, generally a single
correction factor for the attenuation by the tray is applied for each photon beam
quality. In this approach, the tray transmission factor is assumed to be
independent of field size and source-surface distance (SSD). Analysis of a set of
measurements performed in beams of 13 different linear accelerators demonstrates
that there is, however, a slight variation of the tray transmission factor with
field size and SSD. The tray factor changes about 1.5% for collimator settings
varying between 4x4 cm and 40 x 40 cm for a 1 cm thick PMMA tray and
approximately 3% for a 2 cm thick PMMA tray. The variation with field size is
smaller if the source-surface distance is increased. The dependence on the
collimator setting is not different, within the experimental uncertainty of about
0.5% (1 s.d.), for the nominal accelerating potentials and accelerator types
applied in this study. It is shown that the variation of the tray transmission
factor with field size and source-surface distance can easily be taken into
account in the dose calculation by considering the volume of the irradiated tray
material and the position of the tray in the beam. A relation is presented which
can be used to calculate the numerical value of the tray transmission factor
directly. These calculated values can be checked with only a few measurements
using a cylindrical beam coaxial miniphantom.
PMID- 11011742
TI - A noninvasive dose estimation system for clinical BNCT based on PG-SPECT-
conceptual study and fundamental experiments using HPGe and CdTe semiconductor
detectors.
AB - A noninvasive method for measuring the absorbed dose distribution during the
administration of clinical boron neutron capture therapy (BNCT) using an online
three-dimensional (3D) imaging system is presented. This system is designed to
provide more accurate information for treatment planning and dosimetry. The
single-photon emission computed tomography (SPECT) technique is combined with
prompt gamma-ray analysis (PGA) to provide an ideal dose estimation system for
BNCT. This system is termed PG-SPECT. The fundamental feasibility of the PG-SPECT
system for BNCT is confirmed under the following conditions: (1) a voxel size of
1 x 1 x 1 cm3, comparable to the spatial resolution of our standard dosimetric
technique using gold wire activation, where data are available for every 5-10 mm
of wire length; (2) a reaction rate of 10B(n,alpha)7Li within the measurement
volume is greater than 1.1 x l0(6) interactions/cm3/s, corresponding to a thermal
neutron flux of 5 x 10(8) n/cm2/s and a 10B concentration of greater than 10 ppm
for the deepest part of the tumor volume under typical BNCT clinical conditions;
(3) statistical uncertainty of the count rate for 10B(n,alpha)7Li prompt gamma
rays is 10% or less. The desirable characteristics of a detector for the PG-SPECT
system were determined by basic experiments using both HPGe and CdTe
semiconductor detectors. The CdTe semiconductor detector has the greatest
potential for this system because of its compactness and simplicity of
maintenance.
PMID- 11011743
TI - Proton loss model for therapeutic beam dose calculations.
AB - A transport algorithm called the proton loss (PL) model is developed for proton
pencil beams of therapeutic energies. The PL model takes into account inelastic
nuclear reactions, pathlength straggling, and energy-loss straggling and predicts
the 3D dose distribution from a proton pencil beam. In proton beams, the multiple
scattering and ionizational energy loss processes approach their diffusional
limit where scattering and energy loss probability densities become Gaussian.
Therefore we chose to derive the PL model from the Fermi-Eyges diffusional
multiple scattering theory and the Gaussian theory of energy straggling. We first
introduce a generalization of the Fermi-Eyges equation for proton pencil beams,
labeled the proton loss (PL) transport equation. This new equation includes terms
that model inelastic nuclear reactions as a depth-dependent absorption and
pathlength straggling as a quasi-absorption. Then energy straggling is taken into
account by using a weighted superposition of a discrete number of elementary
pencil beams. These elementary pencil beams have different initial energies and
lose energy according to the CSDA, thus they have different ranges of
penetration. A final solution for the proton beam transport is obtained as a
linear combination of elementary pencil beam solutions with weights defined by
the Gaussian evolution of the proton energy spectrum with depth. A numerical
comparison of the dose distribution predictions of the PL model with measurements
and PTRAN Monte Carlo simulations indicates the model is both computational fast
and accurate.
PMID- 11011744
TI - GammaPlan-Leksell Gamma Knife radiosurgery treatment planning verification
method.
AB - This work provides a method for an independent check of Gamma Knife GammaPlan
radiosurgery calculations, named the spherical approximation method or SAM. Based
on skull dimension measurements, the treated volume of the head is modeled as a
sphere of radius R. With this approximation, an analytical solution for fast ray
tracing of the path length, for each of the 201 beamlets, of the Gamma Knife
helmet collimator was possible. The dose rate at the focus of a single shot is
the sum of the contributions of all active beamlets adjusted for both the
collimator factor and attenuation. For an arbitrary point, the dose rate is
derived at the beamlet level from the focus values adjusted for the new path
length attenuation and the appropriate collimators' off-axis profiles. The sum
over all beamlets' contributions gives the dose rate at that particular point. At
the single shot level, SAM independent check results agree with the GammaPlan for
patient calculations to better than +/-6% and, as expected, in spherical phantoms
the agreements improve to better than +/-1.0%. For an arbitrary point, multi-shot
procedure, the agreement is better than +/-3% and +/-1.5, respectively.
PMID- 11011745
TI - Red marrow dosimetry for radiolabeled antibodies that bind to marrow, bone, or
blood components.
AB - Hematologic toxicity limits the radioactivity that may be administered for
radiolabeled antibody therapy. This work examines approaches for obtaining
biodistribution data and performing dosimetry when the administered antibody is
known to bind to a cellular component of blood, bone, or marrow. Marrow dosimetry
in this case is more difficult because the kinetics of antibody clearance from
the blood cannot be related to the marrow. Several approaches for obtaining
antibody kinetics in the marrow are examined and evaluated. The absorbed
fractions and S factors that should be used in performing marrow dosimetry are
also examined and the effect of including greater anatomical detail is
considered. The radiobiology of the red marrow is briefly reviewed.
Recommendations for performing marrow dosimetry when the antibody binds to the
marrow are provided.
PMID- 11011746
TI - Accuracy in catheter reconstruction in computed tomography planning of high dose
rate prostate brachytherapy.
AB - In high dose rate prostate brachytherapy, inadequate reconstruction of catheter
geometry in treatment planning may result in erroneous dose delivery. Catheters
may be digitized with: (1) Parallel reconstruction: digitized at only one point
and assumed parallel and horizontal: (2) Straight reconstruction: digitized at
both ends and assumed straight while at an angle: (3) Slice-by-slice
reconstruction: digitized on all slices to obtain exact geometry. Our results
show that individual catheters are often not parallel to each other, but fairly
straight. Parallel reconstruction is the least accurate for dosimetric planning,
while slice-by-slice reconstruction is time-consuming. Straight (two-point)
reconstruction represents a balance between accuracy and efficiency.
PMID- 11011747
TI - Experimental determination of dosimetric characteristics of Best 125I
brachytherapy source.
AB - 125I brachytherapy sources are being used for interstitial implants in tumor
sites such as the prostate. Recently, the Best 125I source became commercially
available for interstitial brachytherapy treatment. Dosimetric characteristics
(dose rate constant, radial dose function, and anisotropy function) of this
source were experimentally determined, following the AAPM Task Group 43
recommendations, and were related to the NIST 1999 calibration assigned to this
source. Measurements were performed in Solid Water phantom using LiF
thermoluminescent dosimeters. The results indicated a dose rate constant, lambda,
of 1.01 +/- 0.08 cGy h(-1) U(-1) for the new source. The radial dose function,
g(r), of the new source was measured at distances ranging from 0.5 to 10.0 cm.
The anisotropy function, F(r, theta), of the new source was measured at distances
of 2, 5, and 7 cm from the source center. These data compare favorably with those
from the Nycomed/Amersham Models 6711 and 6702 sources. The anisotropy constant,
phi(an), of the Best 125I source was found to be 0.982. Complete dosimetric
parameters of the new source are presented in this paper.
PMID- 11011748
TI - Dosimetric characteristics of the Pharma Seed model BT-125-I source.
AB - 125I brachytherapy sources are being used with increasing frequency for
interstitial implants in tumor sites, especially the prostate. Recently, a new
125I source design has become commercially available for clinical applications.
Dosimetric characteristics (i.e., dose rate constant, radial dose function, and
anisotropy function) of this source were experimentally and theoretically
determined following the AAPM Task Group 43 (TG-43) recommendations and were
related to the 1999 NIST calibration assigned to this source [S(k), 99std].
Measurements were performed in a Solid Water phantom using LiF thermoluminescent
dosimeters. The measured data were used to validate the Monte Carlo simulations
that were performed in Solid Water using the PTRAN code. The Monte Carlo
calculations were then performed in liquid water to obtain the dosimetric
information for clinical applications in accordance with TG-43 recommendations.
The results indicated that the dose rate constant, lambda, of the Pharma Seed
model BT-125-I 125I source was 0.90 +/- 0.06 cGy h(-1) U(-1) using
thermoluminescent dosimeter (TLD) measurements and 0.92 +/- 0.03 cGy h(-1) U(-1)
using Monte Carlo simulations in Solid Water. The calculated value in liquid
water was found to be 0.95 +/- 0.03 cGy h(-1) U(-1). The radial dose function,
g(r), of the new 125I source was measured at distances ranging from 0.5 to 10 cm
using LiF TLD in Solid Water phantom material. The Monte Carlo simulations were
performed for distances ranging from 0.1 to 10 cm from the source center in Solid
Water and liquid water. The anisotropy function, F(r, theta), was measured at
distances of 2, 5, and 7 cm from the source center and calculated at distances of
0.5, 1, 2, 3, 5, and 7 cm from the source center. The anisotropy constant,
phi(an), of the Pharma Seed source in water was found to be 0.975. Complete
dosimetric data are described in this manuscript. Per TG-43, the values reported
in water should be used for clinical treatment planning systems.
PMID- 11011749
TI - A Monte Carlo investigation of the dosimetric characteristics of the CSM11 137Cs
source from CIS.
AB - The purpose of this study is to calculate basic dosimetry data for a CSM11 low
dose rate 137Cs source in water. This source is widely used in afterloadable dome
cylinders designed to homogeneously irradiate the vaginal cuff alone or
additional areas of the vagina in hysterectomized patients. In this study, the
Monte Carlo simulation code GEANT, incorporating in detail source geometry, is
used to investigate the dosimetric characteristics of the source. The calculated
data were analyzed using a fitting procedure that is described in detail.
Absolute dose rate distributions in water were calculated around this source and
are presented as conventional 2D Cartesian lookup tables (classically along-away
tables). Also, the dose calculation formalism endorsed by the Interstitial
Collaborative Working Group and the AAPM Task Group 43 have been calculated. The
calculated dose rate constant for this source is lambda = 1.096 +/- 0.002 cGy h(
1) U(-1). The anisotropy function results in about 50% deviations from isotropy
at positions near the long axis of the source. The radial dose function is given
as a polynomial that reproduces the calculated data up to 20 cm. Best-fit values
of attenuation coefficients suitable for use in Sievert integral calculations
have been derived.
PMID- 11011750
TI - Comment on "In vivo biodistribution of 125IPIP and internal dosimetry of 123IPIP
radioiodinated agents selective to the muscarinic acetylcholinergic receptor
complex" [Med. Phys. 27, 778-786 (2000)].
PMID- 11011751
TI - Comment on "Full breast digital mammography with an amorphous silicon-based flat
panel detector: physical characteristics of a clinical prototype" [Med. Phys. 27,
558-567 (2000)].
PMID- 11011752
TI - Management of asthma exacerbations: home treatment.
AB - Asthma is a major cause of morbidity in children. Delays in care and
inappropriate home management practices can contribute to morbidity and
mortality. Guidelines for the diagnosis and management of asthma were developed
in 1991 and revised in 1997 by The National Heart, Lung and Blood Institute. In
this article we review the recommended pharmacological protocol for home
treatment of asthma exacerbations, and then discuss in more detail behavioral
components of asthma management, including monitoring of symptoms, seeking
medical care, developing clinician-patient partnerships, and practical issues in
equipment and medication usage. Discrepancies between guideline recommendations
and current management practices are also discussed.
PMID- 11011753
TI - Applicability of the Asthma Opinion Survey in the Spanish population:
distribution and relationship with sociodemographic and clinical variables.
AB - We evaluated a Spanish version of the Asthma Opinion Survey (AOS) in a sample of
90 adult Spanish asthma patients. The Spanish AOS showed acceptable internal
consistency, and a factorial structure similar to that reported by others, i.e.,
vulnerability, perceived quality of care, and recognition and control, although
we additional ly obtained a fourth factor, attitudes toward patient knowledge.
Vulnerability was significantly higher among older patients, and among patients
with lower educational level, lower income, and more severe asthma. Perceived
quality of care, and recognition and control were positively correlated with
frequency of attacks, and recognition and control was significantly higher in
older patients. The factor attitudes toward patient knowledge was significantly
higher in younger patients and in patients with relatively high income. These
results support the cross-cultural validity of this questionnaire.
PMID- 11011754
TI - The association of skin test reactivity, total serum IgE levels, and peripheral
blood eosinophilia with asthma in Kuwait.
AB - There is evidence that elevated serum immunoglobulin E (IgE) and eosinophilia
correlate well with allergic skin test reactivity. These parameters have been
used as alternative methods to characterize atopic subjects. Skin test reactivity
is the only measure used routinely in clinical practice in Kuwait to reflect
atopy in asthma patients. This study examines the usefulness of the two other
parameters of atopy in patients with asthma, and to determine the most common
allergens involved in Kuwait. Between 1998 and 1999, 101 asthma patients and 33
healthy controls were recruited for this study. Skin sensitivity test, serum
total and specific IgE, total blood eosinophil count (B-EOS), and eosinophil
cationic protein (ECP) tests were performed in patients and controls. Nine
allergens known to be prevalent in this environment were selected for the skin
test and specific IgE test. Spirometry was also measured. These parameters were
repeated after 4 weeks of therapy in the patients only. Skin test reaction was
positive in 81% of the patients, while total IgE above 200 kU/L was obtained in
63% of cases. B-EOS above 300 x 10(3)/L was found in 75% of cases. House dust
mite reactivity (positivity) was the most frequently encountered skin allergy,
occurring in 28% of the patients. IgE correlated positively with B-EOS and ECP. B
EOS similarly correlated positively with ECP. There was a negative correlation
between ECP and forced expiratory volume in 1 sec (FEV1) (% predicted) as
expected. At least one positive parameter of atopy was found in 95% of the
patients. In 48% of the patients, all three parameters of atopy were found to be
positive. Skin test reactivity and elevated IgE were found together in 62% of the
cases. This study reveals a significant degree of allergy among patients with
asthma in this environment. Skin testing was found to be the most effective
measure of atopy in this environment, and correlates well with the other more
sensitive newer tests.
PMID- 11011755
TI - Assessment of magnesium status in patients with bronchial asthma.
AB - To elucidate the contribution of magnesium to bronchial hyperreactivity in
patients with stable bronchial asthma, magnesium concentrations in serum (S-Mg),
erythrocytes (R-Mg), and lymphocytes (L-Mg) were measured in 25 patients with
bronchial asthma (BA group) and 9 age-matched healthy subjects (control group). A
parenteral magnesium loading test, a continuous low-dose magnesium infusion of
0.2 mEq/kg over 4 hr, was performed in 10 of 25 asthmatic patients and in the
control group. R-Mg was significantly lower in the BA group than in the control
group (4.96 +/- 0.47, 6.13 +/- 0.62 mEq/L, p < 0.001, respectively), although S
Mg (2.4 +/- 0.1, 2.4 +/- 0.2 mg/dL) and L-Mg (1.28 +/- 0.26, 1.15 +/- 0.13
microg/mg/protein) were not significantly different between the two groups.
Magnesium deficiency in total body stores was revealed in 40% of patients (4/10
patients) and 11% of control subjects (1/9 subjects) by parenteral magnesium
loading test. The ratio of magnesium retention to urinary excretion through the
parenteral magnesium loading test showed a significant inverse correlation with R
Mg (r = -0.78, p < 0.01). Bronchial reactivity to inhaled methacholine had a
significant inverse correlation with R-Mg (r = -0.42, p < 0.05). We conclude that
40% of asthmatic patients demonstrated magnesium deficiency, and that the low
magnesium concentration in erythrocytes reflects decreased magnesium stores in
patients with bronchial asthma.
PMID- 11011756
TI - Secretion of adrenocorticotropic hormone induced by allergen inhalation in
patients with atopic asthma.
AB - Allergen inhalation in atopic patients results in cytokines production or release
of preformed cytokines, some of which are known to induce adrenocorticotropic
hormone (ACTH) secretion in experimental conditions. We examined whether allergen
inhalation can induce ACTH secretion in vivo. A significant elevation of ACTH
levels was observed in 2 and 24 hr after allergen inhalation challenge. However,
methacholine challenge with the same degree of airflow limitation did not induce
ACTH elevation, indicating that this may not be due to bronchoconstriction per
se. Our results indicate that allergen inhalation can trigger ACTH secretion in
patients with atopic asthma.
PMID- 11011757
TI - A study of the relationship among self-reported noncompliance, symptomatology,
and psychological variables in patients with asthma.
AB - We examined the association among self-reported noncompliance and clinical
status, symptomatology, functional activity, and psychological variables in
asthma. Eighty-five asthmatics, who were hospitalized (H group), outpatients
previously hospitalized (OH group), or outpatients not previously hospitalized (O
group) completed questionnaires. Compliance was assessed during a structured
interview. The higher prevalence of self-reported noncompliance in H group and OH
group, compared to O group, was not explained by differences in respiratory
function. Self-reported noncompliance was related to symptoms and emotional
distress associated with disease and treatment, but not to functional or
emotional status. A patient subgroup that catalogued itself as noncompliant may
also be at risk for hospitalization, and was characterized by emotional distress
associated with disease and treatment.
PMID- 11011758
TI - Inhaled corticosteroid nonadherence and immediate avoidable medical events in
older adults with chronic pulmonary ailments.
AB - This study examined the association between nonadherence to inhaled
corticosteroids and risk of an immediate avoidable medical event (emergency
department visit and hospitalization) in elderly patients with chronic pulmonary
ailments. The study comprised a cross-sectional analysis comparing patients with
and without avoidable medical event occurrence in each year for adherence
preceding the event, and a case-crossover analysis examining the same patient's
adherence in years with and without events. The cross-sectional study showed risk
odds reductions of nearly 20% in the partially adherent patient, and 40% in the
adherent patient compared to the nonadherent patient, after controlling for
potential group differences.
PMID- 11011759
TI - Knowledge, attitudes, and practices of parents of asthmatic children in Cape
Town.
AB - To obtain information useful to asthma care in a relatively poor, high asthma
prevalence population, a focus group study was undertaken with 72 parents of
children with asthma or recurrent wheezing. There was a reasonable level of
understanding of the causes of asthma, although variable acceptance of the
diagnosis. Willingness to undertake home management of acute episodes and
environmental control measures was high. Reported treatment was characterized by
reliance on syrups, use of home remedies, resistance to inhaled therapy, and
relatively low compliance with prescribed treatment. There was agreement on the
poor level of service offered by doctors and public sector clinics. Asthma
education in this population needs to build on what parents know and accept, but
stress the relative safety of inhaled therapy, the need for maintenance therapy,
and the value of pre-exercise prophylaxis, house dust mite control, and smoking
cessation. There is an urgent need to improve the quality of asthma care provided
by public sector clinics.
PMID- 11011760
TI - Stemming the tide of genomics: computational genomics III.
PMID- 11011761
TI - Relationship between whole proteome aminoacid composition and static DNA
curvature.
AB - To study possible relationships between an organism's genomic DNA curvature and
the aminoacid composition of its proteome, every peptidic sequence from fully
determined genomes was retrotranslated using the E. coli codon preferences, and
the curvature profiles of the resulting DNA sequences were calculated and
compared. A clear interdependence between these two variables was observed, as
each retrotranslated proteome presented a distinctive, statistically significant
DNA curvature profile biased toward its natural DNA curvature profile. In
addition, by comparing the profiles arising from real and randomly permuted
proteomes, we also found a position-dependent contribution of the peptidic
sequence to DNA curvature. The implications of these results support the idea of
a possible selection toward a specific global curvature of genomes.
PMID- 11011762
TI - Improving quality of expressed sequence tag (EST) databases: recovery of
reversed, antisense cDNA sequences.
AB - Expressed sequence tag (EST) databases contain a significant number (5-20%) of
reversed, antisense, cDNA sequences that can be recognized by the label "reversed
clone: similarity on wrong strand" in the annotations to the sequence. Despite
this high number of altered sequences, no attempt has been made to explain the
alteration in molecular terms, or to evaluate their effect on the quality of the
information curated in EST databases. In this paper we try to explain the way
these altered sequences are originated, and propose a plausible mechanism: a
"double priming" of the first strand oligo-dT primer at both ends of nascent
cDNAs. In this way, a symmetrical cDNA intermediate is generated, an intermediate
that can be cloned after partial digestion with the restriction enzyme used for
the directional cloning. Furthermore, when "secondary" priming takes place inside
the cDNA, the chain synthesized is prone to be truncated prematurely, with the
subsequent loss of upstream information. One of the most subtle effects of this
cloning alteration is the generation of virtual open reading frames (ORFs) in
sequences with no homologues available for comparison. Nevertheless, and
according to our model and our data, the "double priming mechanism" does not
shift the ORF effected, so antisense sequences should be considered as normal
ones after a simple transformation in their inverse-complementary forms.
PMID- 11011763
TI - Sequencing of the Francisella tularensis strain Schu 4 genome reveals the
shikimate and purine metabolic pathways, targets for the construction of a
rationally attenuated auxotrophic vaccine.
AB - Francisella tularensis is the etiological agent of tularemia, a serious disease
in several Northern hemisphere countries. The organism has fastidious growth
requirements and is very poorly understood at the genetic and molecular levels.
Given the lack of data on this organism, we undertook the sample sequencing of
its genome. A random library of DNA fragments from a highly virulent strain (Schu
4) of F. tularensis was constructed and the nucleotide sequences of 13,904 cloned
fragments were determined and assembled into 353 contigs. A total of 1.83 Mb of
nucleotide sequence was obtained that had a G+C content of 33.2%. Genes located
on plasmids pOM1 and pNFL10, which had been previously isolated from low
virulence strains of F. tularensis, were absent but all of the other known F.
tularensis genes were represented in the assembled data. F. tularensis Schu4 was
able to grow in the absence of aromatic amino acids and orthologues of genes
which could encode enzymes in the shikimate pathway in other bacteria were
identified in the assembled data. Genes that could encode all of the enzymes in
the purine biosynthetic and most of the en- zymes in the purine salvage pathways
were also identified. This data will be used to develop defined rationally
attenuated mutants of F. tularensis, which could be used as replacements for the
existing genetically undefined live vaccine strain.
PMID- 11011764
TI - Molecular cloning of the Atlantic cod chymotrypsinogen B.
AB - The cDNA encoding Atlantic cod (Gadus morhua) chymotrypsinogen B has been
isolated and sequenced. Its deduced amino acid sequence consists of a 16-residue
signal sequence and a mature polypeptide of 247 residues, being two residues
longer than its vertebrate analogs. This mature polypeptide corresponds to a
calculated molecular mass of 26.5 kDa and shares 70% sequence identity with cod
chymotrypsinogen A. However, the identity between cod chymotrypsinogen B and its
other vertebrate analogues is 63-66%. In common with most fish serine proteases,
cod chymotrypsinogen B contains a high number of methionine residues. The
presence of a threonine instead of a highly conserved serine residue at position
189 is a novel characteristic of this enzyme. Cod chymotrypsin B, as its type B
vertebrate analogs, has an alanine at position 226, whereas a glycine is most
commonly found at this position in the type A chymotrypsins.
PMID- 11011765
TI - Causal analysis of CpG suppression in the Mycoplasma genome.
AB - Some bacterial genomes are known to have low CpG dinucleotide frequencies. While
their causes are not clearly understood, the frequency of CpG is suppressed
significantly in the genome of Mycoplasma genitalium, but not in that of
Mycoplasma pneumoniae. We compared orthologous gene pairs of the two closely
related species to analyze CpG substitution patterns between these two genomes.
We also divided genome sequences into three regions: protein-coding, noncoding,
and RNA-coding, and obtained the CpG frequencies for each region for each
organism. It was found that the observed/expected ratio of CpG dinucleotides is
low in both the protein-coding and noncoding regions; while that ratio is in the
normal range in the RNA-coding region. Our results indicate that CpG suppression
of the Mycoplasma genome is not caused by (1) biased usage amino acid; (2) biased
usage of synonymous codon; or (3) methylation effects by the CpG
methyltransferase in the genomes of their hosts. Instead, we consider it likely
that a certain global pressure, such as genome-wide pressure for the advantages
of DNA stability or replication, has the effect of decreasing CpG over the entire
genome, which, in turn, resulted in the biased codon usage.
PMID- 11011766
TI - Probing biopolymers with the atomic force microscope: a review.
AB - This short review presents an overview of atomic force microscopy (AFM) of
biopolymers and specific examples of some of the biopolymers that have been
analyzed by AFM. These specific examples include extracellular polymeric
substances on the surfaces of bacterial biofilms, condensed DNA, DNA constructs,
and DNA-protein interactions. In addition, two examples are presented for AFM
analyses of proteins: laminin flexing its arms in solution and neurofilaments
entropically brushing away the space around themselves.
PMID- 11011767
TI - Biocompatibility and performance in vitro of a hemostatic gelatin sponge.
AB - The biocompatibility of a hemostatic gelatin sponge (Cutanplast Standard) was
evaluated in vitro. Cytotoxicity was assessed by neutral red uptake and amido
black staining tests; genotoxicity was assayed using the Ames test, Sister
Chromatides Exchanges (SCE) and chromosomal aberrations. The ability of the
hemostatic gelatin sponge to induce platelet adhesion and release reaction was
also determined. The undiluted extract of the test material was found to be
cytotoxic, but cell viability was not affected by 1:2 and 1:10 diluted extract.
The same extract was found to be non-genotoxic using the three assays for
genotoxicity. A significant decrease of platelet number, as well as a significant
release of platelet factor 4 was found to be caused by the solid material. In
conclusion, Cutanplast Standard is neither cytotoxic nor genotoxic, while
inducing platelet adhesion and release reaction when challenged with blood.
PMID- 11011768
TI - Surface characterization and platelet adhesion studies on fluorocarbons prepared
by plasma-induced graft polymerization.
AB - It is believed that the interactions between the biological environment and
biomaterial surface are the key factors influencing its biocompatibility.
Therefore, plasma processing, which can vary the surface properties without
altering the bulk properties, has been considered as one of the important
techniques for improving a materials' biocompatibility. In this investigation,
plasma-induced grafting polymerization of vinylidene fluoride (VDF) and
chlorotrifluoroethylene (CTFE), instead of direct plasma polymerization, was
attempted with an aim to improve the substrate blood compatibility. Contact angle
measurement indicated both fluorocarbon-grafted Pdyethylenes (PEs) are
hydrophobic. Due to the additional fluorine and chlorine atoms on the CTFE chain,
the PCTFE-grafted PE exhibited a higher hydrophobicity than the PVDF-grafted one.
ESCA analysis has revealed that these two plasma-induced fluorocarbon deposits
contain almost no CFx (x > 2) binding on the surface layer, indicating the
grafting polymerization mainly follows the free radical mechanism instead of the
molecule-highly-fragmented reaction steps commonly seen in the direct plasma
polymerization treatment. In addition, ATR-FTIR has shown the surface chemical
configuration of these PVDF- and PCTFE-grafted PEs to be very similar to those of
the bulk samples of PVDF and PCTFE. The surface roughness decreased after oxygen
plasma treatment and was further reduced by VDF and CTFE grafting polymerization.
In vitro platelet adhesion testing indicated these two fluorocarbon grafted PEs
are less platelet-activating than the nontreated PE control and oxygen plasma
activated one.
PMID- 11011769
TI - Extended release peptide delivery systems through the use of PLGA microsphere
combinations.
AB - The purpose of this study was to evaluate the utility of combining polymer
matrices to overcome extended lag periods or unacceptably short durations of
action intrinsic in the individual polymer systems. Leuprolide, an LHRH
superagonist, was incorporated into a variety of poly(lactide-co-glycolide)
(PLGA) matrices using a solvent extraction/evaporation method. The in vitro
release of Leuprolide from these matrices was evaluated at pH 7.0 and 37 degrees
C in phosphate buffer. The formulations were administered to an animal model at 3
or 9 mg kg(-1) doses and serum testosterone levels were followed using a RIA
method. A two-part system was made by combining microspheres made from a 75:25
acid terminated PLGA and microspheres made from a 75:25 ester terminated PLGA.
This combination elicited chemical castration from 10-100 days. A three-part
combination composed of an ester terminated 75:25 PLGA formulation, an ester
terminated 50:50 PLGA formulation and an acid terminated 50:50 PLGA formulation
also provided a composite profile with an onset of 10 days and a duration of
approximately 100 days. Additionally, a single polymer system composed of a high
molecular weight ester terminated 75:25 PLGA was employed to produce release over
the desired 90-day release period. This study demonstrates that microsphere
combinations can potentially provide effective therapies over extended intervals
when combined at the proper ratio.
PMID- 11011770
TI - Intensive promotion of spheroid formation by soluble factors in a hepatocyte
conditioned medium.
AB - We developed a hybrid artificial liver and a drug metabolism simulator using
polyurethane foam (PUF) in which primary hepatocytes spontaneously form
functional spheroids. Gel filtration liquid chromatography analysis of a
hepatocyte-conditioned medium during spheroid formation showed that some
substances secreted by primary rat hepatocytes accumulated advantageously inside
the pores of PUF compared with outside. Similar substances were detected in a
hepatocyte-conditioned medium from a positively-charged surface by concentrating
the substances using an ultrafiltration membrane of a molecular weight-cutoff of
50 kD. These substances were shown to act as soluble factors on freshly isolated
primary rat hepatocytes to promote spontaneous and rapid spheroid formation,
depending on their concentration by preventing them from initially attaching and
spreading on a positively-charged surface. In particular, using 50-fold
concentrated substances, about 80% of total hepatocytes formed the floating
spheroids within 72 h of culture. The resulting spheroids had a diameter
distribution mainly ranging from 40 to 70 microm and expressed high-level liver
specific functions compared with a conventional monolayer.
PMID- 11011771
TI - Self-complex formation of nicotinamide-modified dextran with carboxymethyl
dextran using their degradation products.
AB - A pseudo-metabolic cycle as a self-degradation system was designed: enzymatic
degradation products from a polysaccharide generate oxidants which introduce a
cationic charge into the polysaccharide chains, and can form a polyion complex
with an anionic polysaccharide. As a component of such a system, dextran, with
various degrees of nicotinamide substitution, was prepared. Its degradation by
dextranase, redox reaction via glucose oxidase-catalysis, and polyion complex
formation with carboxymetyl dextran (CMD) were examined. Nicotinamide-modified
dextran (NA-Dex) with nine nicotinamide moieties per 100 glucose units was
soluble in PBS and completely oxidized by > 100 mM H2O2. The oxidized type of NA
Dex was found to form a 1:1 complex with CMD. By the addition of dextranase,
isomaltase, and glucose oxidase (GOD) to phosphate buffer solution of the reduced
type of NA-Dex and CMD, the transmittance of the solution dropped, suggesting
polyion complex formation via the oxidation of 1,4-dihydronicotinamide in NA-Dex
by H2O2 generated from GOD-catalytic reaction. These findings are of great
importance for designing a self-complex formation system aimed at biodegradable
and osillative drug release.
PMID- 11011772
TI - Adhesion and growth of CaCo2 cells on surface-modified PEEK substrata.
AB - A series of surface-functionalized poly(ether ether ketone) (PEEK) films has been
prepared by selective wet-chemistry; they are hydroxylated polymer (PEEK-OH)
obtained by reduction, aminated polymer (PEEK-[]-NH2) prepared by coupling a
diisocyanate reagent to PEEK-OH (PEEK-[]-NCO) followed by hydrolysis, and
carboxylated and aminocarboxylated polymers (PEEK-[]-GABA and PEEK-Lysine)
resulting from the coupling of aminoacids to PEEK-[]-NCO. The aminated and
carboxylated substrata promoted the adhesion and growth of CaCo2 cells in the
presence of serum. Fibronectin (FN), an extra-cellular matrix protein, has been
covalently fixed and/or adsorbed on various PEEK substrata, in the presence or
not of a polymeric surfactant (Pluronic F68). The performances of the FN-grafted
substrata (PEEK-[]-FN(1) and PEEK-[]-FN(2)) were significantly higher than those
of reference substrata simply coated with FN (PEEK-OH(+FN)(1) and (2), PEEK-[]
NH2(+FN)(1) and (2)), considering the adhesion and spreading of CaCo2 cells in
the absence of serum. Moreover, the stability of the adherent cells on the FN
adsorbed substrata dramatically depended on the experimental conditions applied
during the PEEK coating with FN.
PMID- 11011773
TI - Retrograde nailing for subtrochanteric femur fractures.
AB - This study reviews the results of subtrochanteric femur fractures treated with a
retrograde nail at a level 1 trauma center. Sixteen patients with 17 fractures
were followed up until union. The average Injury Severity Score (ISS) was 19, and
average knee range of motion was 127 degrees. Four patients required dynamization
of their nail, and three healed over a prolonged period of time. Two patients
required exchange nailing: one after failure of union after dynamization and one
with a broken nail that was revised to an antegrade nailing. The average varus
deformity was 5.06 degrees and only 35% of fractures healed in greater than 5
degrees of varus, with an average time to union of 22.4 weeks (range, 6-54
weeks). Antegrade nailing remains the treatment of choice for the vast majority
of subtrochanteric femur fractures. However, retrograde femoral nailing may be an
effective treatment option for some subtrochanteric fractures in a selected group
of patients.
PMID- 11011774
TI - The destroyed elbow.
AB - Surgeons need an advanced knowledge of upper extremity anatomy and function to
care for the destroyed elbow. This paper describes strategies for evaluating and
treating this severe injury. Outcomes can be optimized with contemporary
techniques and technologies. Surgeons need to instill realistic expectations in
patients with advanced compromise.
PMID- 11011775
TI - Transsacral versus modified pelvic landmarks for percutaneous iliosacral screw
placement--a computed tomographic analysis and cadaveric study.
AB - The alar roots of the first sacral body are the usual confines for iliosacral
screw (IS) placement when stabilizing a sacroiliac joint injury or sacral
fracture. The traditional transsacral method of IS placement aligns the screw
horizontally through the sacral ala on both the inlet and outlet views of the
sacrum. A modified oblique method of IS placement aligns the screw in an oblique
fashion, directed inferiorly to superiorly and posteriorly to anteriorly. The
purpose of this investigation was to first define the S-1 segment boundaries for
both methods of placement by analyzing the 3-dimensional (3-D) composites of 40
pelvic computed tomography (CT) scans, and then to evaluate the actual placement
of ISs under fluoroscopy in 10 cadaveric pelves comparing the transsacral with
the modified oblique techniques. Critical dimensions of 7.3 mm and 14.6 mm were
considered as the diameter sizes of one and two cannulated screws, respectively.
From the 3-D CT composites, the mean anterior/posterior (A/P) measurements were
10.9 mm and 18.0 mm, comparing transsacral with modified oblique methods,
respectively. Moreover, 9/40 (22.5%) of the transsacral A/P measurements were
<7.3 mm, while all of the modified oblique A/P measurements were >7.3 mm. The
mean superior/inferior (S/I) measurements were 18.0 mm for transsacral and 26.2
mm for modified oblique placement. Out of 40 transsacral S/I measurements, 4
(10%) were <14.6 mm, while all the modified oblique S/I measurements were >14.6
mm. In the second part of this study, 10 uninjured cadaveric pelves had
unilateral percutaneous IS placed under fluoroscopic guidance (inlet, outlet, and
lateral projections) by one orthopedic traumatologist. The final position of all
10 screws was confirmed on fluoroscopy by two independent orthopedic trauma
surgeons. The first 5 screws were placed by using transsacral pelvic landmarks.
Modified landmarks guided the other 5 screws. The accuracy of final screw
position was determined by "postoperative" CT scans interpreted by a blinded
musculoskeletal radiologist. The screws inserted using transsacral pelvic
landmarks were errant in 3 of the 5 cases. Neurovascular complications could be
expected from the extraosseous position of all 3 screws. All 5 screws were
located within the confines of the S-1 segment by means of the modified oblique
technique. Thus, the modified oblique placement technique allowed greater
accuracy and reliability over transsacral landmarks in placing percutaneous ISs.
The use of the modified oblique pelvic landmarks is warranted during percutaneous
iliosacral screw stabilization of the posterior pelvis.
PMID- 11011777
TI - Evaluation and treatment of high subtrochanteric femur fractures.
AB - This retrospective study reviews the biomechanical factors and surgical
approaches for the treatment of high subtrochanteric femur fractures to determine
whether management should be directed toward using an intramedullary or
extramedullary device. Results have demonstrated that both plates and
intramedullary implants work equally well, with intramedullary implants resulting
in significant decreases in surgical times and blood losses. Because
intramedullary devices can now be placed through percutaneous trochanteric
insertions, they have become more attractive for the management of these
injuries. However, intramedullary devices may be difficult to use in fractures
presenting with a trochanteric extension, and adjunctive reduction techniques are
still required to obtain fracture reductions and prevent varus malunions. When
deciding on which technique to use, surgeons should evaluate the fracture pattern
and determine whether the implants and techniques that are familiar to them will
allow good functional outcomes, high rates of unions, and low rates of
complications.
PMID- 11011776
TI - Free-flap reconstruction of traumatic lower extremity wounds.
AB - A retrospective review of 20 free-tissue transfers for reconstruction of
traumatic lower extremity wounds was undertaken. The wounds consisted of Gustilo
type IIIb injuries resulting from motor vehicle accidents, falls, motorcycle and
four-wheel, all-terrain vehicle accidents, and a laceration from a lawnmower
blade. Fifty percent of the procedures were for open tibia fractures. The most
common flap used was the rectus abdominis, followed by the latissimus dorsi,
serratus anterior, and radial forearm. There were two major complications
resulting in flap loss. Adequate and multiple debridements, selection of the
appropriate flap, meticulous surgical technique, and postoperative care continue
to be the essentials of free-flap coverage. With a motivated patient, limb
salvage and return to function can be achieved after most high-energy injuries.
PMID- 11011778
TI - Femoral recon nails for metastatic disease: indications, technique, and results.
AB - The senior author has used 41 femoral recon nails of one design in 41 consecutive
patients with 30 impending and 11 pathologic femur fractures. All nails were
inserted with minimally invasive surgical technique. The hospital stay was
shorter (average, 5.6 days) and discharge to home was more likely (77%) after
stabilization of impending pathologic fractures compared with fixation of
completed fractures (length of hospital stay averaged 7.8 days, with a 36%
discharge-to-home rate), as patients with completed fractures required a higher
level of postoperative care. Fixation prior to fracture occurrence results in
predictably better early results than that of fixation after fracture occurrence,
confirming the benefit of prophylactic fixation of impending pathologic
fractures. To date, there have been no fixation failures and only one significant
complication: a nonfatal pulmonary embolus. This technique provides a safe and
effective method of stabilizing properly selected femoral lesions resulting from
metastatic disease, especially impending pathologic fractures.
PMID- 11011779
TI - Impact of enteral and parenteral nutrition on hepatic and muscle glucose
metabolism.
AB - Liver and muscle metabolism were assessed in dogs adapted to long-term total
parenteral (TPN) and enteral (TEN) nutrition. Studies were done in 13 conscious
long-term catheterized dogs in which sampling (artery, portal and hepatic vein,
and iliac vein), infusion catheters (inferior vena cava, duodenum), and transonic
flow probes (hepatic artery, portal vein, and iliac artery) were implanted.
Fourteen days after surgery dogs were grouped to receive TPN or TEN. After 5 days
of TPN/TEN, substrate balances across the liver and limb were assessed. The liver
was a marked net consumer of glucose in both groups (23.6 +/- 3.3 vs 22.6 +/- 2.8
micromol x kg(-1) x min(-1), TPN vs TEN) despite near normoglycemia (6.5 +/- 0.3
vs 6.7 +/- 0.2 mmol/L). Arterial insulin levels were higher during TEN (96 +/- 6
vs 144 +/- 30 pmol/L; p < .05). The majority (79 +/- 13 vs 76% +/- 7%) of the
glucose taken up by the liver was released as lactate. Despite higher insulin
levels during TEN the nonsplanchnic tissues consumed a lessor quantity of glucose
(25.9 +/- 3.3 vs 16.1 +/- 3.9 micro x mol x kg(-1) x min(-1)). In summary, the
liver undergoes a profound adaptation to TPN and TEN making it a major site of
glucose uptake and conversion to lactate irrespective of the route of nutrient
delivery. However, the insulin requirements are higher with TEN possibly
secondary to impaired peripheral glucose removal.
PMID- 11011780
TI - Individual neuropeptides regulate gut-associated lymphoid tissue integrity,
intestinal immunoglobulin A levels, and respiratory antibacterial immunity.
AB - BACKGROUND: Total parenteral nutrition (TPN) leads to atrophy of the gut
associated lymphoid tissue (GALT) and a significant decrease in intestinal
immunoglobulin A (IgA) levels, a major constituent of mucosal immunity. Bombesin
(BBS) prevents TPN-induced GALT atrophy and maintains intestinal IgA levels. BBS,
a neuropeptide analogous to gastrin-releasing peptide in humans, stimulates the
release of other gut neuropeptides including cholecystokinin (CCK), gastrin, and
neurotensin (NT). This study investigates the ability of CCK, gastrin, or NT to
individually prevent TPN-induced GALT atrophy and preserve respiratory immunity.
METHODS: Experiment 1: Male mice were randomly assigned to receive chow, TPN, TPN
plus CCK, TPN plus gastrin, or TPN plus NT. After 5 days of feeding, Peyer's
patches (PP) from the proximal and distal small bowel were harvested and analyzed
for cell yields. PP cells were also analyzed for GALT cell type. Small bowel IgA
levels were measured by enzyme-linked immunosorbent assay (ELISA). Experiment 2:
Mice were randomly assigned to receive either liposomes containing Pseudomonas
antigen or liposomes without antigen. After 10 days, mice were randomly assigned
to the same five treatment groups, fed for 5 days, and then given intratracheal
Pseudomonas. Mortality was assessed after 48 hours. RESULTS: Experiment 1: GALT
cell reductions due to IV-TPN were greater in the distal than proximal small
bowel. All three neuropeptides prevented most TPN-induced GALT atrophy due mainly
to the maintenance of the B-cell and T-cell populations in the PP of the distal
bowel. Intestinal IgA levels were significantly higher in the animals treated
with neuropeptides than animals treated with TPN only; however, these IgA levels
were not maintained at levels observed in chow-fed animals. Experiment 2:
Immunization resulted in significantly lower mortality in animals fed chow, TPN
plus CCK, and TPN plus gastrin. TPN alone and TPN plus NT resulted in loss of
immunity and mortality rate at comparable levels to unimmunized animals.
CONCLUSIONS: Supplementation of IV-TPN with CCK, gastrin, and NT prevents GALT
atrophy, primarily in the distal bowel. Intestinal IgA levels improve but not to
normal levels. CCK and gastrin reversed IV-TPN-induced effects on antibacterial
pneumonia in immunized animals while NT did not.
PMID- 11011782
TI - Malnutrition impairs CD11b/CD18 expression on circulating polymorphonuclear
neutrophils and subsequent exudation into inflammatory sites in the early phase
of glycogen-induced murine peritonitis.
AB - BACKGROUND: The effects of malnutrition on polymorphonuclear neutrophil (PMN)
exudation are not well understood. The purpose of this study was to examine the
effects of short-term dietary restriction on adhesion molecule expression on
circulating PMNs and PMN exudation into the inflamed site in a glycogen-induced
peritonitis model. METHODS: Twelve mice were randomly assigned to one of two
groups. The ad libitum and diet-restricted groups received mouse chow ad libitum
(estimated consumption: 132 g/kg per day) and 33 g/kg per day, respectively, for
7 days. Then, 2 mL of a 1% glycogen solution was intraperitoneally administered
to all mice. After 4 hours, the animals were killed. Whole blood was drawn by
cardiac puncture. Peritoneal exudative cells were harvested by lavaging the
peritoneal cavity. Expressions of CD11b, CD18, and CD62L were measured by flow
cytometry. RESULTS: Dietary restriction did not affect the numbers of circulating
leukocytes, PMNs, or monocytes. However, CD11b and CD18 expressions on
circulating PMNs were significantly lower in the diet-restricted than in the ad
libitum group. In contrast, CD62L expression on circulating PMNs was not affected
by dietary restriction. The number of exudative PMNs was significantly lower in
the diet-restricted group than in the ad libitum group. The expressions of CD11b,
CD18 and CD62L on exudative PMNs were unaffected by dietary restriction. There
was a significant positive correlation between exudative PMN numbers and CD18
expression on circulating PMNs. CONCLUSIONS: Severe dietary restriction in our
murine model decreased beta2 integrin expression on circulating PMNs and
inhibited PMN exudation into inflamed sites in the early phase of inflammation.
These events may increase susceptibility to bacterial infection. Nutritional
replenishment may improve host defense in part by enhancing PMN adhesion molecule
expression.
PMID- 11011781
TI - Glutamine-enriched total parenteral nutrition maintains intestinal interleukin-4
and mucosal immunoglobulin A levels.
AB - BACKGROUND: Total parenteral nutrition (TPN) prevents progressive malnutrition
but fails to maintain intestinal gut-associated lymphoid tissue (GALT) or
established respiratory antiviral or antibacterial mucosal immunity. Our previous
work demonstrated that decreases in intestinal immunoglobulin A (IgA) were
associated with decreases in Th2-type IgA-stimulating cytokines, interleukin (IL)
4 and IL-10. Because glutamine supplementation of TPN partially preserves
respiratory defenses and normalizes GALT, we investigated the ability of
parenteral glutamine to normalize respiratory and intestinal IgA levels and
measured Th2 cytokines in intestinal homogenates. METHODS: Animals were
cannulated and randomly assigned to receive chow (n = 17), TPN (n = 18), or an
isonitrogenous, isocaloric TPN solution formulated by removing the appropriate
amount of amino acids and replacing them with 2% glutamine (n = 18) for 5 days.
Respiratory tract and intestinal washings were obtained for IgA and the intestine
homogenized and analyzed for IL-4 and IL-10. RESULTS: TPN decreased intestinal
and respiratory IgA in association with decreases in intestinal IL-4 and IL-10
compared with chow-fed animals. Glutamine significantly improved respiratory and
intestinal IgA levels, significantly improved IL-4 compared with TPN animals, and
maintained IL-10 levels midway between chow-fed and TPN animals. CONCLUSIONS:
Glutamine-enriched TPN preserved both extraintestinal and intestinal IgA levels
and had a normalizing effect on Th2-type IgA-stimulating cytokines.
PMID- 11011783
TI - Arginine supplementation is well tolerated but does not enhance mitogen-induced
lymphocyte proliferation in elderly nursing home residents with pressure ulcers.
AB - BACKGROUND: Immune function declines with age, increasing risk for infection and
delaying wound healing. Arginine enhances immune function and healing of
standardized wounds in healthy elderly persons. The purpose of this study was to
determine what level of arginine supplementation was orally and metabolically
tolerated and effective in enhancing immune function in elderly persons with
pressure ulcers. METHODS: Residents with one or more pressure ulcers were
recruited from two local nursing homes. Subjects were randomized to receive 0 g
(n = 10; age, 82 +/- 3 years), 8.5 g (n = 11; 81 +/- 3 years), or 17 g (n = 11;
87 +/- 2 years) of supplemental arginine each day for 4 weeks. Oral tolerance,
ie, absence of nausea, vomiting, abdominal distention, or diarrhea, was assessed
daily. Metabolic tolerance was assessed weekly by evaluating serum electrolytes.
Lymphocyte proliferation to phytohemagglutinin and interleukin 2 production were
measured at baseline and after 4 weeks of supplementation as indicators of immune
function. RESULTS: Supplemental arginine significantly increased plasma arginine
levels and was orally and metabolically tolerated with no complaints of abdominal
distress or no clinically relevant changes in electrolyte levels among groups.
Lymphocyte proliferation and interleukin 2 production were significantly
different between nursing homes. When data from nursing homes were considered
individually, arginine supplementation did not enhance the proliferative
response. In subjects from nursing home 2 only, there was a 38% and 75% decrease
(p < .05) in lymphocyte proliferation with 8.5 and 17 g of supplemental arginine,
respectively. Interleukin 2 production was no different among supplementation
groups. CONCLUSIONS: Pharmacologic doses of arginine were well tolerated but did
not enhance lymphocyte proliferation or interleukin 2 production in nursing home
residents with pressure ulcers. CLINICAL RELEVANCY: Enteral formulas supplemented
with pharmacologic levels of arginine are frequently administered to elderly
persons. This study demonstrates that the very old can tolerate these nitrogen
loads if baseline renal function is normal and fluid intake is encouraged.
Further research needs to be completed investigating the effect of arginine
supplementation on immune function in this population before recommending
arginine use.
PMID- 11011784
TI - Enterotrophic effect of insulin-like growth factor-I but not growth hormone and
localized expression of insulin-like growth factor-I, insulin-like growth factor
binding protein-3 and -5 mRNAs in jejunum of parenterally fed rats.
AB - BACKGROUND: Administration of insulin-like growth factor (IGF)-I, but not growth
hormone (GH), stimulates mucosal hyperplasia in surgically stressed rats with
intestinal atrophy induced by hypocaloric total parenteral nutrition (TPN). Our
aim was to characterize the basis for this disparity in enterotrophic action by
assessing the relationships between stimulation of intestinal growth, nutritional
adequacy, and localization of expression of IGF-I, insulin-like growth factor
binding protein (IGFBP)-3 and IGFBP-5 mRNAs in jejunum. METHODS: Rats were
maintained with TPN for 8 days and treated with IGF-I or GH and adequate
nutrition for 5 days after recovery from surgery. Jejunal mass, morphology, and
sucrase activity were assessed. Localization of expression of IGF-I, IGFBP-3, and
IGFBP-5 mRNAs in jejunum was accomplished by in situ hybridization. RESULTS:
Serum IGF-I and body weight gain were significantly increased by IGF-I or GH.
Jejunal mucosal dry mass, morphology, and sucrase activity were improved with IGF
I but not GH. There were no differences in IGF-I mRNA. IGFBP-3 mRNA was localized
in the lamina propria of the villi. IGF-I or GH stimulated IGFBP-3 expression.
IGF-I strongly stimulated IGFBP-5 expression in the lamina propria and the
muscularis and induced a twofold increase in IGFBP-5 mRNA based on RNase
protection assay of intact jejunum total RNA. GH induced a modest increase in
IGFBP-5 expression in the muscularis with no effect on intact jejunum total RNA.
CONCLUSIONS: The GH resistance observed in the jejunal mucosa of TPN rats cannot
be fully explained by inadequate nutrition. The expression of IGFBP-5 in the
lamina propria suggests it may modulate the enterotrophic action of exogeneous
IGF-I.
PMID- 11011785
TI - Hazard analysis and critical control point system approach in the evaluation of
environmental and procedural sources of contamination of enteral feedings in
three hospitals.
AB - BACKGROUND: The administration of contaminated diets may contribute to severe
infections, mainly in immunosuppressed patients. To determine the microbiologic
quality of enteral feedings and the critical control points involved in the
processing of the formulas, a study was carried out in three hospitals in Sao
Paulo, Brazil. METHODS: One hundred sixteen diets were evaluated according to the
system known as hazard analysis and critical control points (HACCP). The
techniques included the monitoring of the cleaning and disinfection of utensils,
surfaces, and equipment; time and temperature controls; and microbiologic
analyses that comprised the enumeration of facultative aerobic mesophilic
bacteria, yeasts and molds, coliforms, and Escherichia coli. The diets were
assessed based on the British Dietetic Association and the Food and Drug
Administration standards. RESULTS: The hospital-formulated diets and the
commercially made powdered feeds presented statistically significant higher
counts of mesophilic bacteria and percentages of no compliance with the standards
for coliforms when compared with the commercially prepared, ready-to-feed enteral
formula supplied in cans. According to the British standards, 77% and 38% of the
diets were inadequate for mesophilic and coliform bacteria, respectively, just
after preparation. After 24-hour storage in refrigerators, the percentages rose
to 83% and 45%, respectively; the mesophilic and coliforms counts were also
significantly higher. The following critical control points (CCP) were
identified: cleaning and disinfecting of surfaces, utensils, and equipment; the
time spent in preparation; the water used for reconstitution; the final
temperature of the diet; the exposure to room temperatures; the lack of a
chilling step; the refrigeration temperature; the inadequate disinfecting of the
handlers' hands; and the lack of external cleaning and disinfecting of the cans
before opening. CONCLUSIONS: The results of this study are worrisome and show the
need for implementation of good practices of hygiene and handling of the diets,
and the regular monitoring of their preparation. The microbiologic quality of the
enteral diets was compromised according to international standards, representing
a potential risk of infection to the patients who require enteral nutrition.
PMID- 11011786
TI - A multicenter, prospective study of the placement of transpyloric feeding tubes
with assistance of a magnetic device. The Magnet-Guided Enteral Feeding Tube
Study Group.
AB - BACKGROUND: Placement of feeding tubes in the transpyloric position can be
helpful in the management of enterally fed patients with pancreatitis, gastric
atony, enterocutaneous fistulae, or pulmonary aspiration risk. The attainment of
transpyloric position is difficult, and numerous techniques have been proposed to
help in achieving this location. Recently, the use of a magnet-tipped feeding
tube, dragged into proper position with an external magnet, has been described
with an excellent success rate. METHODS: At 10 participating institutions,
practitioners were trained in the use of the device. Successful tube placement
was determined by abdominal radiograph. RESULTS: One hundred fifty-six tube
placements were attempted. Transpyloric position was obtained in 60%. Placement
into the third portion of the duodenum or distal was obtained in only 32%.
Analysis of the data did not reveal a learning curve at the institutions, and 7
of 10 had a 50% or lower success rate. CONCLUSIONS: Placement of feeding tubes
with the assistance of a magnetic device was infrequently successful at the
majority of institutions where it was attempted. We report a lower success rate
than the original article, which described an 88% success rate of transpyloric
intubation. Although this technique has a high failure rate, some individuals
seem to be very successful using it, which could reduce the need for endoscopy or
transport for the placement of feeding tubes.
PMID- 11011787
TI - A novel efficient method to identify beta-glucuronidase activity in rat small
intestine.
AB - BACKGROUND: Recent epidemiologic studies promote the notion that high intake of
food rich in phytochemicals protects against degenerative diseases such as
coronary heart diseases and cancer. Phytochemicals are detoxified in mammalian
tissues by conjugation with glucuronic acid yielding less active glucuronide
conjugates. However, in several tissues glucuronide conjugates are reactivated by
the cleaving enzyme beta-glucuronidase. The aim of the present study was to
develop a routinely manageable, rapid technique to localize the beta
glucuronidase activity in the small intestinal tissue. METHODS: Histologic slices
of rat duodenum, jejunum, and ileum were incubated with a specific chromogenic
beta-glucuronidase substrate, 5-bromo-4-chloro-3-indolyl-beta-D-glucuronide (X
GlcU). After enzymatic cleavage, X-GlcU yields 5-bromo-4-chloro-3-indol, a dark
blue crystalline precipitate easily monitored by light microscopic technique.
RESULTS: The number and intensity of the crystals were highest in the jejunum and
lowest in the ileum. In all three sections of the small intestine, the highest
activity was observed at the villar tip and in the tela submucosa and only
moderate activity in other layers of the intestinal tissue. CONCLUSIONS: By using
the X-GlcU-technique, it could be demonstrated convincingly that beta
glucuronidase exists in all three segments of the rat small intestine. The
proposed method is an efficient, simple, and convenient method to visualize beta
glucuronidase activity.
PMID- 11011788
TI - Digital VLSI algorithms and architectures for support vector machines.
AB - In this paper, we propose some very simple algorithms and architectures for a
digital VLSI implementation of Support Vector Machines. We discuss the main
aspects concerning the realization of the learning phase of SVMs, with special
attention on the effects of fixed-point math for computing and storing the
parameters of the network. Some experiments on two classification problems are
described that show the efficiency of the proposed methods in reaching optimal
solutions with reasonable hardware requirements.
PMID- 11011789
TI - Implementation of a pulse coupled neural network in FPGA.
AB - The Pulse Coupled neural network, PCNN, is a biologically inspired neural net and
it can be used in various image analysis applications, e.g. time-critical
applications in the field of image pre-processing like segmentation, filtering,
etc. a VHDL implementation of the PCNN targeting FPGA was undertaken and the
results presented here. The implementation contains many interesting features. By
pipelining the PCNN structure a very high throughput of 55 million neuron
iterations per second could be achieved. By making the coefficients re
configurable during operation, a complete recognition system could be implemented
on one, or maybe two, chip(s). Reconsidering the ranges and resolutions of the
constants may save a lot of hardware, since the higher resolution requires larger
multipliers, adders, memories etc.
PMID- 11011791
TI - VLSI implementation of neural networks.
AB - Currently, fuzzy controllers are the most popular choice for hardware
implementation of complex control surfaces because they are easy to design.
Neural controllers are more complex and hard to train, but provide an outstanding
control surface with much less error than that of a fuzzy controller. There are
also some problems that have to be solved before the networks can be implemented
on VLSI chips. First, an approximation function needs to be developed because
CMOS neural networks have an activation function different than any function used
in neural network software. Next, this function has to be used to train the
network. Finally, the last problem for VLSI designers is the quantization effect
caused by discrete values of the channel length (L) and width (W) of MOS
transistor geometries. Two neural networks were designed in 1.5 microm
technology. Using adequate approximation functions solved the problem of
activation function. With this approach, trained networks were characterized by
very small errors. Unfortunately, when the weights were quantized, errors were
increased by an order of magnitude. However, even though the errors were
enlarged, the results obtained from neural network hardware implementations were
superior to the results obtained with fuzzy system approach.
PMID- 11011790
TI - A programmable VLSI filter architecture for application in real-time vision
processing systems.
AB - An architecture is proposed for the realization of real-time edge-extraction
filtering operation in an Address-Event-Representation (AER) vision system.
Furthermore, the approach is valid for any 2D filtering operation as long as the
convolutional kernel F(p,q) is decomposable into an x-axis and a y-axis
component, i.e. F(p,q)=H(p)V(q), for some rotated coordinate system [p,q]. If it
is possible to find a coordinate system [p,q], rotated with respect to the
absolute coordinate system a certain angle, for which the above decomposition is
possible, then the proposed architecture is able to perform the filtering
operation for any angle we would like the kernel to be rotated. This is achieved
by taking advantage of the AER and manipulating the addresses in real time. The
proposed architecture, however, requires one approximation: the product operation
between the horizontal component H(p) and vertical component V(q) should be able
to be approximated by a signed minimum operation without significant performance
degradation. It is shown that for edge-extraction applications this filter does
not produce performance degradation. The proposed architecture is intended to be
used in a complete vision system known as the Boundary-Contour-System and Feature
Contour-System Vision Model, proposed by Grossberg and collaborators. The present
paper proposes the architecture, provides a circuit implementation using MOS
transistors operated in weak inversion, and shows behavioral simulation results
at the system level operation and electrical simulation and experimental results
at the circuit level operation of some critical subcircuits.
PMID- 11011792
TI - Convergence analysis of cascade error projection--an efficient learning algorithm
for hardware implementation.
AB - In this paper, we present a mathematical foundation, including a convergence
analysis, for cascading architecture neural network. Our analysis also shows that
the convergence of the cascade architecture neural network is assured because it
satisfies Liapunov criteria, in an added hidden unit domain rather than in the
time domain. From this analysis, a mathematical foundation for the cascade
correlation learning algorithm can be found. Furthermore, it becomes apparent
that the cascade correlation scheme is a special case from mathematical analysis
in which an efficient hardware learning algorithm called Cascade Error
Projection(CEP) is proposed. The CEP provides efficient learning in hardware and
it is faster to train, because part of the weights are deterministically
obtained, and the learning of the remaining weights from the inputs to the hidden
unit is performed as a single-layer perceptron learning with previously
determined weights kept frozen. In addition, one can start out with zero weight
values (rather than random finite weight values) when the learning of each layer
is commenced. Further, unlike cascade correlation algorithm (where a pool of
candidate hidden units is added), only a single hidden unit is added at a time.
Therefore, the simplicity in hardware implementation is also achieved. Finally, 5
to 8-bit parity and chaotic time series prediction problems are investigated;
the simulation results demonstrate that 4-bit or more weight quantization is
sufficient for learning neural network using CEP. In addition, it is demonstrated
that this technique is able to compensate for less bit weight resolution by
incorporating additional hidden units. However, generation result may suffer
somewhat with lower bit weight quantization.
PMID- 11011793
TI - Simulink-based HW/SW codesign of embedded neuro-fuzzy systems.
AB - We propose a semi-automatic HW/SW codesign flow for low-power and low-cost Neuro
Fuzzy embedded systems. Applications range from fast prototyping of embedded
systems to high-speed simulation of Simulink models and rapid design of Neuro
Fuzzy devices. The proposed codesign flow works with different technologies and
architectures (namely, software, digital and analog). We have used The Mathworks'
Simulink environment for functional specification and for analysis of performance
criteria such as timing (latency and throughput), power dissipation, size and
cost. The proposed flow can exploit trade-offs between SW and HW as well as
between digital and analog implementations, and it can generate, respectively,
the C, VHDL and SKILL codes of the selected architectures.
PMID- 11011794
TI - Automating parallel implementation of neural learning algorithms.
AB - Neural learning algorithms generally involve a number of identical processing
units, which are fully or partially connected, and involve an update function,
such as a ramp, a sigmoid or a Gaussian function for instance. Some variations
also exist, where units can be heterogeneous, or where an alternative update
technique is employed, such as a pulse stream generator. Associated with
connections are numerical values that must be adjusted using a learning rule, and
and dictated by parameters that are learning rule specific, such as momentum, a
learning rate, a temperature, amongst others. Usually, neural learning algorithms
involve local updates, and a global interaction between units is often
discouraged, except in instances where units are fully connected, or involve
synchronous updates. In all of these instances, concurrency within a neural
algorithm cannot be fully exploited without a suitable implementation strategy. A
design scheme is described for translating a neural learning algorithm from
inception to implementation on a parallel machine using PVM or MPI libraries, or
onto programmable logic such as FPGAs. A designer must first describe the
algorithm using a specialised Neural Language, from which a Petri net (PN) model
is constructed automatically for verification, and building a performance model.
The PN model can be used to study issues such as synchronisation points, resource
sharing and concurrency within a learning rule. Specialised constructs are
provided to enable a designer to express various aspects of a learning rule, such
as the number and connectivity of neural nodes, the interconnection strategies,
and information flows required by the learning algorithm. A scheduling and
mapping strategy is then used to translate this PN model onto a multiprocessor
template. We demonstrate our technique using a Kohonen and backpropagation
learning rules, implemented on a loosely coupled workstation cluster, and a
dedicated parallel machine, with PVM libraries.
PMID- 11011795
TI - FPNA: interaction between FPGA and neural computation.
AB - Neural networks are usually considered as naturally parallel computing models.
But the number of operators and the complex connection graph of standard neural
models can not be directly handled by digital hardware devices. More
particularly, several works show that programmable digital hardware is a real
opportunity for flexible hardware implementations of neural networks. And yet
many area and topology problems arise when standard neural models are implemented
onto programmable circuits such as FPGAs, so that the fast FPGA technology
improvements can not be fully exploited. Therefore neural network hardware
implementations need to reconcile simple hardware topologies with complex neural
architectures. The theoretical and practical framework developed, allows this
combination thanks to some principles of configurable hardware that are applied
to neural computation: Field Programmable Neural Arrays (FPNA) lead to powerful
neural architectures that are easy to map onto FPGAs, thanks to a simplified
topology and an original data exchange scheme. This paper shows how FPGAs have
led to the definition of the FPNA computation paradigm. Then it shows how FPNAs
contribute to current and future FPGA-based neural implementations by solving the
general problems that are raised by the implementation of complex neural networks
onto FPGAs.
PMID- 11011796
TI - Effects of hyperbaric oxygen on ventricular performance, pulmonary blood volume,
and systemic and pulmonary vascular resistance.
AB - The cardiovascular effects of hyperbaric (3 atm abs) air, 100% oxygen, and
hyperbaric oxygen (HBO2) at 3 atm abs were investigated in 13 pentobarbital
anesthetized dogs. We measured heart rate, arterial pressure, pulmonary artery
pressure, right atrial pressure, left and right ventricular pressure, and cardiac
output. From these we determined end diastolic pressure, +/-maximal dp/dt,
maximal (dp/p), end systolic elastance, cardiac work, and systemic (SVR) and
pulmonary vascular resistance (PVR). Pulmonary blood volume was obtained from the
mean transit time of ascorbic acid. The significant results with HBO2 were a
decrease in heart rate, cardiac output, and cardiac work. All left ventricular
performance indices decreased, without a change in preload or afterload. In
contrast, only right ventricular -dp/dt decreased. SVR increased but PVR did not
change; 100% O2 produced similar but less pronounced responses. Hyperbaric air
had only mild effects. Pulmonary blood volume and lung wet/dry ratio did not
change. Our data suggest that HBO2 may act by a differential effect on the
autonomic innervation of the right and left ventricles. The resultant ventricular
imbalance may be of clinical importance in the mechanism of pulmonary edema in
patients in congestive heart failure undergoing hyperbaric therapy.
PMID- 11011797
TI - Influence of gender and menstrual cycle on a cold air tolerance test and its
relationship to thermosensitivity.
AB - This investigation evaluated the influence of gender and phase of menstrual cycle
[follicular (FOL): Days 2-6) and luteal (LUT: Days 19-24)] on a cold air
tolerance test (CATT: 90-min of exposure to 5 degrees C air) in 8 females (22.7
+/- 3.0 yr) and 15 males (22.3 +/- 2.9 yr). In addition, central
thermosensitivity (beta; W x kg(-1) x degrees C(-1) [i.e., the slope of the
relationship between the decrease in esophageal temperature (Tes) and the
increase in heat production (HP)], gathered during a separate water trial in 20
degrees C water, was correlated to the change (delta) in Tes and HP across the 90
min of resting exposure during the CATT. Analysis of variance revealed no
significant differences between phase of menstrual cycle or gender for HP, mean
skin temperature (Tsk), and insulation; however, a main effect for time for these
parameters was demonstrated. Despite these similarities, Tes differed (P < 0.05)
between males and females. Additionally, no relationship was found between beta
and deltaHP and deltaTes in the males and females. Also, there was no
relationship between beta and thermoregulation during the CATT in these subjects.
These data suggest that menstrual cycle phase did not cause a differential
response in Tes, Tsk, and HP during a CATT. Furthermore, women maintained a
higher Tes than men during the CATT despite similarities in HP and Tsk.
PMID- 11011798
TI - Effects of smoking on cost and duration of hyperbaric oxygen therapy for diabetic
patients with non-healing wounds.
AB - During this study to determine the effects of smoking on diabetic patients
undergoing hyperbaric oxygen therapy (HBO2T) for nonhealing wounds, one physician
visited five hyperbaric facilities and reviewed records on 1,006 patients who had
received HBO2T for diabetic wounds. Smoking history was documented on 469
patients, while 180 patients had complete information on number of HBO2Ts,
outcome, age, duration of diabetes, transcutaneous oxygen baseline in air at
ambient conditions, Wagner score of the worst wound, smoking history, and
intensity of treatment. These factors were statistically significant predictors
of treatment outcome using multiple regression modeling. No difference was found
between smokers with less than 10 pack-years of cumulative history and
nonsmokers. After that point there was a significant increase in the number of
HBO2Ts needed to produce at least some healing in smokers vs. patients who had
never smoked. The average patient with a greater than 10 pack-year smoking
history who benefited from treatment was estimated to need between 8 and 14 more
HBO2Ts. This translates into an added treatment cost of $4,000 to $7,000 for the
average patient who has smoked, and an estimated $22-37 million annually for the
United States.
PMID- 11011799
TI - Hearing function in a hyperbaric environment.
AB - Navy divers' hearing function was assessed as part of three saturation deep dives
to 1,000 feet of sea water (fsw) to determine explanations for threshold shifts
observed under hyperbaric conditions. Across the three deep dives, different
aspects of the ear were evaluated, including air- and bone-conduction pure-tone
thresholds, real ear probe microphone measurements, auditory evoked potentials,
and central auditory processing assessments. Attempts to measure middle ear
function and cochlear function (through otoacoustic emissions) were unsuccessful.
Baseline measurements were obtained at 0 fsw in air before and after the
saturation deep dives. Results showed that some aspects of hearing function
remained unchanged with increases in depth. In general, audiometric thresholds at
depth were similar to those measured on the surface at 500, 1,000, 2,000, 3,000,
and 4,000 Hz. However, hearing sensitivity actually improved at depth at 6,000
and 8,000 Hz. The use of a specially designed sound booth for a pressurized
heliox environment yielded significantly lower ambient noise levels and improved
the accuracy of threshold measurement. Auditory evoked potential measurements and
central auditory processing function were relatively unaffected by changes in
depth. Significant changes at depth were seen in ear canal resonance which
shifted up in frequency; this finding was attributed to the effect of helium on
the hearing mechanism. Because objective measurement of middle ear and inner ear
function were not methodologically possible, questions still remain regarding the
interpretation of middle and inner ear function at depth. Nonetheless, our
overall findings suggest that most aspects of hearing functioning are similar
under high atmospheric pressures and in heliox as they are on the surface, with
the exception of shifts in ear canal resonance and improvements in audiometric
thresholds at high frequencies.
PMID- 11011800
TI - Performance of the Baxter Flo-Gard 6201 volumetric infusion pump for monoplace
chamber applications.
AB - For non-hyperbaric purposes, the Baxter Flo-Gard 6201 volumetric pump is capable
of infusing multiple types of fluids at rates of 1-1,999 ml x h(-1). We designed
a study to determine flow accuracy of this pump at variable rates, fluid
viscosities, and volumes over a range of chamber pressures. For hyperbaric use,
the pump pressure sensor was adjusted. Sodium chloride solution 0.9% (NS),
enteral formula, and packed red blood cells (PRBC) were infused at varying rates
from 86.1 to 304 kPa (0.85 to 3.0 atm abs). For NS, measured compared to set flow
rates ranged from 12.5% to -7.5% at settings of 1 and 5 ml x h(-1) from 86.1 to
304 kPa (0.85 to 3.0 atm abs) pressures, respectively. For NS infusions at a set
rate of 100 ml x h(-1), the measured flow was identical to the set rate at all
pressures. At flow settings of 1,999 ml x h(-1), the measured flow varied from
the set flow by +/-4.9% Enteral infusion at 100 ml x h(-1) showed approximately a
3% increase in the measured vs. set flow rate. PRBC measured flow rates ranged
from -0.4 to 6% of the set rate. During chamber compression and decompression,
with set flow rates from 1 to 10 ml x h(-1), the measured flow was considerably
less than expected during compression and more than expected during
decompression. In conclusion, the Baxter Flo-Gard 6201 infusion pump demonstrated
acceptable performance for infusing saline, enteral formula, and PRBC at low and
high infusion rates into the pressurized monoplace hyperbaric chamber up to 304
kPa (3 atm abs), with the exception of low rates during compression and
decompression.
PMID- 11011801
TI - Heparins in the new millennium: will unfractionated heparin survive?
Introduction.
PMID- 11011802
TI - An update on heparins at the beginning of the new millennium.
AB - Unfractionated heparin has enjoyed the sole anticoagulant status for almost half
a century. Besides an effective anticoagulant, this drug has been used in several
additional indications. Despite the development of newer anticoagulant drugs,
unfractionated heparin has remained the drug of choice for surgical
anticoagulation and interventional cardiology. In the area of hematology and
transfusion medicine, unfractionated heparin has continued to play a major role
as an anticoagulant drug. The development of low-molecular-weight heparins
(LMWHs) represents a refinement for the use of heparin. These drugs represent a
class of depolymerized heparin derivatives with a distinct pharmacologic profile
that is largely determined by their composition. These drugs produce their major
effects by combining with antithrombin and exerting antithrombin and anti-Xa
inhibition. In addition, the LMWHs also increase non-antithrombin-dependent
effects such as TFPI release, modulation of adhesion molecules, and release of
profibrinolytic and antithrombotic mediators from the blood vessels. The
cumulative effects of each of the different LMWHs differ and each product
exhibits a distinct profile. Initially these agents were developed for the
prophylaxis of postsurgical deep-vein thrombosis. However, at this time these
drugs are used not only for prophylaxis, but also for the treatment of thrombotic
disorders of both the venous and arterial type. To a large extent, the LMWHs have
replaced unfractionated heparin in most subcutaneous indications. With the use of
these refined heparins, outpatient anticoagulant management has gone through a
dramatic evolution. For the first time, patients with thrombotic disorders can be
treated in an outpatient setting. Thus, the introduction of LMWHs represents a
major advance in improving the use of heparin. The development of the oral
formulation of heparin and LMWHs also provides an important area that may impact
on the use of heparin and LMWHs. The increased awareness of heparin-induced
thrombocytopenia has necessitated the development of newer methods to identify
patients at risk of developing this catastrophic syndrome. Furthermore, a strong
interest has developed in alternate drugs or the management of patients with this
syndrome. Despite the development of alternate anticoagulants that are mostly
antithrombin derived (hirudins, hirulog), these agents have failed to provide
similar clinical outcome as heparin in many indications. However, antithrombin
drugs are useful in the anticoagulant management of heparin-compromised patients.
The FDA has approved a recombinant hirudin (Refludan) and a synthetic
antithrombin agent, argatroban (Novastan), for this indication. The development
of synthetic heparin pentasaccharide and anti-Xa agents may have an impact on the
prophylaxis of thrombotic disorders. However, these monotherapeutic agents do not
mimic the polytherapeutic actions of heparin. Furthermore, these agents do not
inhibit thrombin. Heparin and LMWHs are capable of inhibiting not only factor Xa
and thrombin, but other serine proteases in the coagulation network. The only way
the newer drugs can mimic the actions of heparin is in combination modalities
(polytherapeutic approaches). It has been suggested that newer antiplatelet drugs
also exhibit anticoagulant actions. While these drugs may exhibit weak effects on
thrombin generation, none of the currently available antiplatelet drugs exhibit
any degree of antithrombin actions. It is likely that heparins synergize or
augment the effects of the new antiplatelet drugs. Currently, combination
approaches are used to anticoagulate patients in these studies. The dosage of
heparins has been arbitrarily reduced. This may not be an optimal procedure.
Additional clinical studies are needed to study these combinations where the
alterations of these drugs are compared. Such combinations will require newer
monitoring approaches. The development of oral thrombin agents, GP IIb
PMID- 11011803
TI - Development of tinzaparin: a heparinase-digested low-molecular-weight heparin.
AB - Although heparin and its properties had been discovered in the early 1920s, the
different characteristics associated with different molecular-weight fractions of
heparin were only recognized in the late 1970s. Tinzaparin is a low-molecular
weight heparin (LMWH) produced by heparinase digestion of heparin. Preclinical
research on tinzaparin established that there were no differences in the
antithrombotic activity compared with heparin. Clinical studies evaluating
tinzaparin vs. standard heparin for thromboprophylaxis of deep-vein thrombosis in
general and orthopedic surgery found that tinzaparin was as effective as standard
heparin. Tinzaparin was also evaluated vs. standard heparin in the treatment of
acute proximal vein thrombosis; time-to-event curves suggested that this LMWH
could be more effective than standard heparin.
PMID- 11011804
TI - Comparative pharmacokinetics of LMWHs.
AB - A variety of pharmaceutical preparations of low-molecular-weight heparins (LMWHs)
are available. They belong to the same family of compounds-ie, heparin
derivatives with a narrow distribution of mean molecular weights (MWs). LMWHs
have different methods of preparation, which result in variations in mean MW,
distribution of MW, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles.
The mean MW of these compounds ranges from 3,600 to 6,500 daltons. The ratio of
anti-Xa (aXa) and anti-IIa (aIIa) activities of the different LMWHs ranges from
1.5 to >10. After subcutaneous (SC) injection of a prophylactic or therapeutic
dose, the peak values for plasma aXa or aIIa activity may vary twofold to
threefold because of differences in bioavailability, plasma clearance (Clplasma),
and half-life (t1/2). The injection of equivalent amounts of product, based on
aXa and aIIa international units (IU), may result in different areas under the
curve for the respective activities. Although tinzaparin has a high aIIa specific
activity per milligram (and consequently, a low aXa/aIIa ratio), SC injection of
40 mg of enoxaparin (4,000 aXa IU) results in a higher aXa peak value in patients
with total hip replacement than 4,500 aXa IU of tinzaparin. Differences in aIIa
and aXa peak activities are more striking when high doses of LMWHs are used. The
activated partial thromboplastin time (aPTT) can be significantly prolonged, an
effect that is related to aIIa and aXa activity. The volume of distribution of
LMWHs is of the same order of magnitude as that of the plasma volume. The mean
retention time of aXa activity varies from 5.2 (dalteparin) to approximately 7 h
(enoxaparin, nadroparin). Bioavailability of prophylactic doses of LMWHs ranges
from 86% (dalteparin) to 98% (enoxaparin, nadroparin). PK parameters appear to be
minimally affected by a patient's age. The Clplasma is different for each LMWH:
16 mL/min enoxaparin, 21 mL/min nadroparin, 33 mL/min dalteparin, 19 mL/min
reviparin, and 22 mL/min tinzaparin. Accumulation of product has been observed
for almost all LMWHs in patients with renal insufficiency. LMWHs are effective
and safe for treatment or prophylaxis of venous thromboembolism during pregnancy,
because they do not cross the placenta. No data are available regarding the
passage of LMWHs into the milk in lactating women. Although LMWHs are also
effective in prevention and treatment of thromboembolic disease in children,
optimal use of these agents in pediatric patients has not been determined. In
summary, the PD and PK of LMWHs have been well documented and have demonstrated
that LMWHs have a more predictable response, a greater bioavailability, and a
longer aXa t1/2 than unfractionated heparin. However, their distribution of MW
affects their physicochemical and biological properties, as well as PK
characteristics. The concept of aXa/aIIa ratio (determined in vitro) does not
account for the differing PK of aXa and aIIIa activity in circulating blood.
PMID- 11011805
TI - Comparative efficacy of different low-molecular-weight heparins (LMWHs) and drug
interactions with LMWH: implications for management of vascular disorders.
AB - The low-molecular-weight heparins (LMWHs) are more efficacious and safer than
unfractionated heparin (UFH) in the prevention and treatment of venous thrombosis
and to a certain extent in the treatment of acute ischemic syndromes. Because of
their predictable pharmacokinetics and bioavailability after subcutaneous
administration, LMWHs can be more convenient for outpatient use than UFH.
Differences in the manufacturing process of LMWHs result in significant
structural and molecular weight differences; thus, LMWHs have individual
biochemical and pharmacological profiles and are not interchangeable on the basis
of either mass or anti-Xa activity. Using thromboelastograph (TEG) and platelet
aggregometry, this investigation compared the in vitro efficacy among various
LMWHs and examined the interactions between LMWHs and platelet glycoprotein (GP)
IIb/IIIa antagonists. TEG was used to determine the ability of platelet and
fibrin interactions to augment blood clots, an effect measured under conditions
of maximal platelet activation during clot formation accelerated by recombinant
human tissue factor (TF). The comparative efficacy of LMWHs on different mediator
induced clot retraction in human blood was assessed by TEG, which demonstrated
the potency of different LMWHs to inhibit various mediator-induced clot
formations under shear. Tinzaparin was relatively more effective in inhibiting TF
, lipopolysaccharide-, factor (f) Xa-, and thrombin-induced clot formation under
shear. Under these conditions, platelets significantly enhance clot strength
(eightfold vs. platelet-free fibrin clots). LMWHs appear to have broader efficacy
than other anticoagulants. Abciximab and roxifiban further inhibited clot
strength by affecting the transmission of platelet contractile force to fibrin by
platelet GPIIb/IIIa receptors. Subtherapeutic doses of tinzaparin combined with
abciximab or roxifiban resulted in a distinct synergy that improved anticoagulant
and antiplatelet efficacy mediated by TF, fXa, or thrombin. As these data
suggest, the combination of low-dose tinzaparin with low-dose GPIIb/IIIa
antagonists (abciximab, roxifiban) may be efficacious in the prevention and
treatment of various thromboembolic disorders.
PMID- 11011806
TI - Prophylaxis and treatment of deep-vein thrombosis.
AB - In 1980, unfractionated heparin (UFH) was the established agent for the
prophylaxis of venous thromboembolic (VTE) disease in patients undergoing general
surgery. VTE prophylaxis was the first indication in which low-molecular-weight
heparins (LMWHs) were tested. Approximately 40 trials have demonstrated that
LMWHs are at least as effective and safe as UFH. LMWHs exhibit a number of
advantages over UFH, including ease of administration, convenient once-daily
dosing, and facilitation of outpatient management. The ideal time of
administration and the dose of the initial one or two injections of LMWH remain
unresolved issues. LMWHs are used with increasing frequency in the treatment of
acute deep vein thrombosis (DVT), having been studied in comparison to UFH in 16
major clinical trials. LMWHs are at least as effective as UFH in the prevention
of VTE, but higher doses than those used for prophylaxis are required. There is
still an ongoing debate about whether the daily dose should be administered in
one or two subcutaneous injections. In some recent studies, symptomatic new DVTs
or pulmonary emboli (PE) were the primary end points, which had to be verified by
objective methods, but such end points may be not be sensitive enough to detect
major differences in the efficacy of different LMWHs.
PMID- 11011807
TI - Comparative efficacy of low-molecular-weight heparins in orthopedic surgery.
AB - The low-molecular-weight heparins (LMWHs) have been evaluated in the prevention
of postoperative thromboembolic disease and have been found to be clinically
efficacious and safe. Studies conducted in similar surgery settings have resulted
in significantly different reductions in the incidence of deep-vein thrombosis,
making an analysis of grouped studies complex. Only two studies have reported
head-to-head comparisons of two different LMWHs and showed no difference in
clinical end points between enoxaparin and either reviparin or tinzaparin. Our
study at the Aalborg hospital in Denmark, comparing two different dosage regimens
of LMWH tinzaparin, supported the conclusions of the head-to-head comparative
studies. LMWHs are distinct drug entities that cannot be interchanged at
equivalent anti-Xa dosages, and the interpretation of their relative efficacy and
safety may be biased by the degree of clinical experience of the individual
investigators.
PMID- 11011808
TI - An equivalence study of two low-molecular-weight heparins in the prevention and
treatment of deep-vein thrombosis after total hip replacement.
AB - Low-molecular-weight heparins have been evaluated against unfractionated heparin
and have been shown to have clinical benefits in the perioperative setting during
orthopedic surgery. Two low-molecular-weight heparins, tinzaparin and enoxaparin,
were assessed for equivalency in efficacy and safety in 499 patients undergoing
elective hip replacement. The two anticoagulants were found to be effective and
safe in this setting in the specified patient type. No statistical difference was
observed in the incidence of bleeding. Clinical side effects tended to be greater
in patients with a higher body mass index, which could serve as a possible
indicator for the risk of deep vein thrombosis.
PMID- 11011809
TI - Low-molecular-weight heparin in the treatment of venous thromboembolism.
AB - The low-molecular-weight heparins (LMWHs) have been evaluated in the prevention
and treatment of deep-vein thrombosis and pulmonary embolism. LMWHs have been
found to be safe and effective in this clinical setting and have advantages over
unfractionated heparin. These advantages include less serious and less frequent
therapeutic complications. The favorable pharmacokinetic profile of LMWHs
compared with heparin has allowed for safe, effective, and convenient treatment
of patients with venous thromboembolism. Use of LMWHs ultimately results in
considerable cost savings for the health care system.
PMID- 11011810
TI - Low-molecular-weight heparin and cancer.
AB - Heparin is a familiar anticoagulant drug with properties that may impede tumor
growth; it modifies properties of cells that contribute to malignant
dissemination such as angiogenesis, growth factor and protease activity, immune
function, proliferation, and gene expression. Heparin has antitumor effects in
animal models of malignancy, and studies in human malignancy show improved cancer
outcome with heparin treatment. Meta-analyses comparing unfractionated heparin
(UFH) and low-molecular-weight heparin (LMWH) for treatment of deep-vein
thrombosis have shown apparent substantial improvement in cancer outcome in the
subset of patients with malignancy who were randomly assigned to receive LMWH.
This experience, together with the favorable pharmacokinetic properties of LMWH,
provides a rationale for prospective clinical trials of LMWH in patients with
cancer. Such trials should provide (a) definitive data on possible antitumor
effects of this treatment, (b) insight into possible heterogeneous responses to
heparin treatment among different histological types and stages of malignancy,
and (c) a setting for exploring mechanisms of antineoplastic effect in human
malignancy.
PMID- 11011812
TI - Heparins in the new millennium: will unfractionated heparin survive? Epilogue.
PMID- 11011811
TI - Antithrombotics and anticoagulants in coronary syndromes and stroke.
AB - The low-molecular-weight heparins (LMWHs) have been proven superior to placebo in
reducing the incidence of acute coronary ischemic syndromes. Comparative studies
vs. unfractionated heparin have not demonstrated superiority in favor of the LMWH
dalteparin. In the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave
Coronary Events (ESSENCE) trial, enoxaparin was demonstrated to have a benefit
over heparin. The results have contributed to a better understanding of the
relative efficacy of LMWHs in acute coronary syndromes. A second trial with
enoxaparin supported the conclusions of the ESSENCE trial. The antithrombotic
effects of LMWHs have also been evaluated for the management of ischemic stroke
with varied results. A trial assessing tinzaparin in acute ischemic stroke has
completed enrollment, and its results may shed new light on the use of an LMWH
for the management of stroke.
PMID- 11011813
TI - CHOP Infant Coma Scale ("Infant Face Scale"): a novel coma scale for children
less than two years of age.
AB - The Glasgow Coma Scale (GCS) is the most frequently used tool worldwide for
assessing the severity of neurologic injury after brain trauma, although applying
this scale to infants and younger children can be problematic. The CHOP Infant
Coma Scale, or Infant Face Scale (IFS), is a novel scale for children under 2
years of age which differs from other pediatric coma scales in the following
ways: (1) it relies on objective behavioral observations; (2) it assesses
cortical as well as brainstem function; (3) it parallels the GCS in scoring but
is based on infant-appropriate behaviors; and (4) it can be applied to intubated
patients. We report the results of a prospective study designed to compare
interrater reliability between the IFS and GCS in children less than 2 years of
age. Seventy-five hospitalized children less than 2 years of age were assessed
simultaneously by a pair of observers, representing a spectrum of health care
professionals, who scored the children using both the IFS and GCS. Interrater
reliability for each pair of observers for each scale was assessed using the
kappa statistic. A second series of 10 infants in the intensive care unit with
specific diagnoses of acute traumatic or hypoxic/ischemic brain injury were
similarly assessed. In the 75 hospitalized infants with a variety of diagnoses,
interrater reliability for the GCS was in the "almost perfect," "slight," and
"fair" range for the eye-opening, motor, and verbal subtests, respectively. In
contrast, the IFS showed interrater reliability in the "almost perfect,"
"substantial," and "almost perfect" ranges for the three subtests. When applied
to infants in an intensive care unit with acute traumatic brain injury or
hypoxia/ischemia, the GCS interrater reliability scores were in the "fair" range,
while the IFS scores were in the "almost perfect" range. The IFS demonstrates
improved interrater reliability in direct comparison to the GCS, particularly in
the "verbal/face" component where most pediatric coma scales are deficient. The
IFS may prove to be a simple and practical bedside index of brain injury severity
in children less than two years of age.
PMID- 11011814
TI - Inhibition of neocortical plasticity during development by a moderate concussive
brain injury.
AB - To determine if a moderate traumatic brain injury (TBI) sustained early in life
alters the capacity for developmental plasticity, 17-20-day-old rat pups received
a lateral fluid percussion and then reared in an enriched environment for 17
days. Compared to sham-injured controls, this moderate TBI prevented the increase
in cortical thickness (1.48 vs. 1.68 mm, p < 0.01) as well as the corresponding
enhancement in cognitive performance in the Morris Water Maze (39 vs. 25 trials
to criterion, p < 0.05). These injured animals exhibited no significant neuronal
degeneration and no evidence of neurologic or motor deficits. These findings
strongly support the conclusion that a diffuse brain injury is capable of
inhibiting both anatomical and cognitive manifestations of experience-dependent
developmental plasticity.
PMID- 11011815
TI - Role of nociceptin/orphanin FQ in age-dependent cerebral hemodynamic effects of
brain injury.
AB - This study was designed to compare the role of the newly described endogenous
opioid nociceptin/orphanin FQ (NOC/oFQ) in the reductions of cerebral blood flow
(CBF) and pial artery diameter observed following fluid percussion brain injury
(FPI) in chloralose anesthetized newborn and juvenile pigs as a function of time
postinsult. FPI elevated CSF NOC/oFQ concentration from 70 +/- 3 to 444 +/- 51
within 1 h and to 1,931 +/- 112 pg/mL (n = 7) within 8 h, whereas concentrations
returned to control value within 168 h in the newborn. In contrast, FPI elevated
CSF NOC/oFQ from 77 +/- 4 to 202 +/- 16 pg/mL (n = 7) within 1 h, while values
returned to control value within 8 h in the juvenile. Topical NOC/oFQ (10(-8),
10(-6) M) induced vasodilation was reversed to vasoconstriction by FPI in the
newborn while such responses were only attenuated in the juvenile at 1 h post
insult (control, 9 +/- 1 and 16 +/- 1%; FPI newborn, -8 +/- 1 and -14 +/- 1%; FPI
juvenile, 2 +/- 1 and 5 +/- 1%, n = 7). Such altered dilation returned to control
value within 168 h in newborns and 8 h in juveniles. Blood flow in the cerebrum
was reduced from 57 +/- 4 to 23 +/- 3 mL x min(-1) x 100 g(-1) (n = 7) within 1 h
and returned to control value with 168 h post FPI in newborns. In animals
pretreated with [F/G] NOC/oFQ (1-13) NH2 (1 mg/kg, i.v.), a NOC/oFQ antagonist,
however, CBF only fell to 39 +/- 4 mL x min(-1) x 100 g(-1) (n = 7) at 1 h post
insult in newborns. In contrast, CBF was only reduced from 57 +/- 6 to 32 +/- 2
in untreated and to 39 +/- 3 mL/min(-1) x 100 g(-1) (n = 7) in treated juveniles
within 1 h post FPI. Similar observations for reductions in pial artery diameter
were made in untreated and treated newborns and juveniles. These data suggest
that an elevated CSF NOC/oFQ concentration and altered vascular responsiveness to
this opioid contribute to reductions in CBF and pial artery diameter observed
following FPI. Because such NOC/oFQ changes were greater in newborns versus
juveniles, these data further suggest that NOC/oFQ contributes to age-related
cerebral hemodynamic differences in the effects of FPI.
PMID- 11011816
TI - Spinal cord injury "outliers": an analysis of etiology, outcomes, and length of
stay.
AB - Spinal cord injury (SCI) requires significant and expensive medical intervention,
including prolonged hospitalization and intense in-patient treatment and
rehabilitation. Development of predictive models for lengths of stay in spinal
cord injury patients provides a method for early prediction of patients that will
require greater care, incur greater costs, and need more intensive medical and
rehabilitative services. Early identification of SCI patients at high risk of
extended lengths of stay will also allow physicians to treat those patients more
aggressively, and permit families, as well as sponsors, to estimate the costs of
long-term care. Results of a forward-conditional stepwise multiple logistic
regression indicate that the model including age at injury, number of days to
rehabilitation admission, number of pressure ulcers, number of medical
complications, level of injury, and sponsor of initial hospitalization
significantly (chi2 = 220.063, p < 0.001) predicts outliers in terms of
rehabilitation length of stay. Overall, the percentage of persons who were
correctly classified by the multivariate model was 96.92% (chi2 = 66.85, p <
0.001). The correct prediction rate for outliers was 46% and nonoutliers 97%.
This model provides a tool that can be used by health providers, sponsors and
patients to aid in the identification of individuals with SCI that may require
extended lengths of stay. Today, unfortunately, our health care system is
burdened by the heavy influence of economics rather than functional outcome. We
maintain that implementation of this model will help to improve care of the SCI
patient by early identification of those in need of more extensive resources and
improve the economic efficiency needed to provide maximal functional outcome.
PMID- 11011817
TI - Riluzole and methylprednisolone combined treatment improves functional recovery
in traumatic spinal cord injury.
AB - The potential use of riluzole (a glutamate release inhibitor) alone or in
combination with methyl-prednisolone (MP) in treating acute spinal cored injury
(SCI) was examined. Rats received a contusion injury to the spinal cord using the
NYU impactor and were treated with vehicle, riluzole (8 mg/kg), MP(30 mg/kg), or
riluzole + MP at 2 and 4 h following injury. Animals continued to receive
riluzole treatment (8 mg/kg) for a period of 1 week. The animals were then tested
weekly for functional recovery using the BBB open field locomotor score. At the
end of testing (6 weeks after injury), each spinal cord was examined for the
amount of remaining tissue at the injury site and a myelination index was used to
quantify remaining axons in the ventromedial white matter. In this study, only
the combination treatment was found to significantly improve behavioral recovery
as assessed using the BBB open field locomotor scale. In addition, the
combination treatment promoted tissue sparing at the lesion epicenter, but had no
clear effect on the index of myelination. The results of this study clearly
demonstrate the potential beneficial effects of a combination approach in the
treatment of traumatic SCI.
PMID- 11011818
TI - Schwannosis: role of gliosis and proteoglycan in human spinal cord injury.
AB - Schwannosis (aberrant proliferation of Schwann cells and nerve fibers) has been
reported following spinal cord injury (SCI). In this study, we examined the
incidence of schwannosis following human SCI, and investigated its relationship
to gliosis. We found evidence of schwannosis in 32 out of 65 cases (48%) of human
SCI that survived 24 h to 24 years after injury; this incidence rose to 82% in
those patients who survived for more than 4 months. Schwannosis was not observed
in cases that survived less than 4 months after injury. In affected cases, it was
generally noted in areas that had low immunoreactivity for glial fibrillary
acidic protein (GFAP), suggesting that reduced gliosis might have contributed to
the aberrant proliferation of Schwann cells following SCI. Since chondroitin
sulfate proteoglycan (CSPG) has been proposed to play a role in Schwann
cell/glial interaction, we performed immunohistochemical staining for CSPG to
investigate its potential relationship with schwannosis. CSPG in the injured cord
was generally associated with the blood vessel walls, but was also sometimes
noted in reactive astrocytes. In SCI with schwannosis, CSPG staining was more
prominent and confined largely to the extracellular matrix and basal lamina of
proliferating Schwann cells. Our study suggests that Schwann cells, which may
have been displaced from spinal roots and introduced into the injured cord
through a break in the pial surface, are capable of proliferating and producing
CSPG, particularly in the setting of reduced gliosis. Since CSPG has been
associated with inhibition of neurite outgrowth, its increased production by
aberrant Schwann cells may impair spinal cord regeneration after injury.
PMID- 11011819
TI - Effect of liposome-mediated macrophage depletion on Schwann cell proliferation
during Wallerian degeneration.
AB - The axolemma is considered a well-established mitogen, responsible for Schwann
cell proliferation during Wallerian degeneration in the peripheral nerve.
However, very little is known about the role of macrophages in Schwann cell
proliferation. To test the possible influence of macrophages on Schwann cell
proliferation during Wallerian degeneration, macrophages were depleted by
dichloromethylene diphosphonate (CI2MDP)-containing liposomes in two-month old
C57BL/6J mice. CI2MDP-containing liposomes were injected into the mice
intravenously prior to inducing Wallerian degeneration. The injection was
repeated every other day to maintain macrophage depletion. Physiologic saline was
injected into the control mice. To assess macrophage depletion in vitro, cells
were isolated from sciatic nerves at 1, 2, 3, 5, and 7 days post-transection
(DPT) and Mac-1 positive cells attached to coverslips were counted. In an in vivo
study, Mac-1 positive cells were counted on sciatic nerve sections at the same
time points. Throughout the course, the number of Mac-1 positive cells in
macrophage-depleted mice was less than that in the control mice both in vivo and
in vitro. Schwann cell proliferation was assessed by an in vitro system that
reflects in vivo status at the time of cell isolation. Schwann cells were
isolated from sciatic nerves at the same time points and proliferation rate was
measured by thymidine autoradiography. The proliferation rate was mildly
suppressed in macrophage-depleted mice, especially for the initial 3 DPT;
however, the pattern of proliferation was not significantly different from
controls. These results suggest that macrophages contribute to Schwann cell
proliferation during Wallerian degeneration however, their contribution may be
relatively limited.
PMID- 11011820
TI - The clinical features of severe community-acquired pneumonia presenting as septic
shock. Norasept II Study Investigators.
AB - PURPOSE: The purpose of this article was to determine the outcome, clinical and
prognostic features, and microbiology of a large group of patients with community
acquired pneumonia (CAP) presenting in septic shock. MATERIALS AND METHODS: The
placebo limb of the Norasept II database was examined. Data were collected on
patients in septic shock with a diagnosis of CAP who presented to a participating
site from home. RESULTS: One hundred and forty-eight patients met the study
criteria. The 28-day survival was 53%. One hundred and four pathogens were
isolated from 77 (52%) patients with 24 (16%) patients having polymicrobial
infections. The most common pathogen was Streptococcus pneumoniae (19%), followed
by Staphylococcus aureus (18%), Haemophilus influenzae (14%), Klebsiella
pneumoniae (11%), and Pseudomonas aeruginosa (7%). Infection with P aeruginosa or
Acinetobacter species carried a very high mortality (82%). The only clinical
variables recorded in the database that could identify patients with pseudomonas
or acinetobacter infection was a history of alcohol abuse. Comorbidities were
present in 74% of patients, involving predominantly the cardiorespiratory system.
Logistic regression analysis demonstrated APACHE II score and serum interleukin 6
(IL-6) concentration to be significant independent predictors of mortality.
Patients with pseudomonas or acinetobacter infection had significantly higher IL
6 levels and significantly lower tumor necrosis factor alpha levels when compared
with the rest of the cohort of patients. CONCLUSION: A diverse spectrum of both
gram-positive and gram-negative pathogens were implicated in patients with CAP
presenting in septic shock, necessitating broad spectrum empiric antimicrobial
coverage. This coverage should include antipseudomonal activity, particularly in
alcoholic patients. Severity of illness (APACHE II score) and IL-6 levels were
important prognostic factors. Infection with P aeruginosa and Acinetobacter
species carried a very high mortality.
PMID- 11011821
TI - Acute respiratory distress syndrome: resource use and outcomes in 1985 and 1995,
trends in mortality and comorbidities.
AB - PURPOSE: The purpose of this study was to compare resource consumption and
mortality between (ARDS) patients with adult respiratory distress syndrome
treated at our center in 1985 (45 patients) and those treated in 1995. MATERIALS
AND METHODS: This was a retrospective observational study, considering trauma and
nontrauma ARDS separately. We recorded severity index scores (APACHE III),
infectious complications and multiorgan failure, intensive care unit (ICU)
resource consumption (TISS 28), length of stay, time on mechanical ventilation,
and ICU mortality. RESULTS: We found no variation in overall ARDS mortality and
no reduction in mortality in the ARDS trauma group (43.5% in 1985 vs. 38.5% in
1995, not significant) but a significant increase in mortality among nontrauma
septic ARDS patients (68.2% vs. 82.9%, P < .001), largely attributable to the new
comorbidities of human immunodeficiency virus (HIV) infection and hematologic
malignancy. TISS-28 showed an overall reduction over this time period (49.7 +/-
6.6 vs. 38.3 +/- 9.7, P < .001), due to fewer monitoring measures, particularly a
lower use of pulmonary artery catheter. There were no overall changes in length
of stay or days on mechanical ventilation between 1985 and 1995, but these
variables did increase among the trauma subgroup. CONCLUSION: In our setting,
mortality remained constant from 1985 to 1995 among ARDS trauma patients but not
among nontrauma ARDS patients because of the new case-mix of the latter
population, which now includes HIV and other immunodepressed patients.
PMID- 11011822
TI - Influence of amrinone on intestinal villus blood flow during endotoxemia.
AB - PURPOSE: The objective of this study was to determine the effects of a continuous
infusion of the phosphodiesterase (PDE) inhibitor amrinone on mucosal villus
blood flow in a normotensive model of endotoxemia. MATERIALS AND METHODS: Twenty
four anesthetized and ventilated rats underwent laparotomy, and an ileal portion
was exteriorized and opened by an antimesenteric incision. The ileal segment was
fixed on a plexiglass stage with the mucosal surface upward. Microcirculatory
parameters were assessed by intravital videomicroscopy. The animals were randomly
assigned to receive one of three treatments: infusion of Escherichia coli
lipopolysaccharides (LPS, 2 mg/kg/h) without phosphodiesterase inhibitor
pretreatment (LPS group); or infusion of LPS with amrinone pretreatment (40
microg/kg/min, start 30 minutes before LPS infusion) (amrinone group), or
infusion of equivalent volumes of NaCl 0.9% (control group). Macrohemodynamic
parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean
diameter of central arterioles = D(A) and mean erythrocyte velocity within the
arterioles = VE) were measured 30 minutes before and at 0, 60, and 120 minutes
after induction of endotoxemia. Mucosal villus blood flow was calculated from
D(A) and VE. RESULTS: In this normotensive endotoxemia model, MAP remained stable
in the control and the LPS group but significantly decreased in the amrinone
group.The endotoxin-induced decrease of V(E) and D(A) of central arterioles of
mucosal villi could be attenuated and prevented, respectively. Thus, the
endotoxin-induced decrease of mucosal villus blood flow was diminished but not
fully restored by amrinone infusion. CONCLUSION: Our results indicate that
amrinone during an early stage of sepsis is of limited value. It attenuates
mucosal hypoperfusion but contributes to systemic hypotension.
PMID- 11011823
TI - Partial liquid ventilation shows dose-dependent increase in oxygenation with PEEP
and decreases lung injury associated with mechanical ventilation.
AB - PURPOSE: The purpose of this article is to evaluate the effect of positive end
expiratory pressure (PEEP) during partial liquid ventilation (PLV) and to
investigate if lung damage associated with mechanical ventilation can be reduced
by PLV. MATERIALS AND METHODS: Twenty-two New-Zealand white rabbits were
ventilated in pressure-controlled mode maintaining constant tidal volume (10
mL/kg). Lung injury was induced by repeated saline lavage (PaO2 < 100 mm Hg). Two
incremental PEEP steps maneuvers (IPSMs) from 2 to 10 cm H2O in 2 cm H2O steps
were performed sequentially. The control group received the first IPSM in the
supine position and were turned prone for the second IPSM. In the PLV group (n =
7), 12 mL/kg of perfluorodecalin was instilled after lung injury before the two
IPSMs. The early prone group (n = 7) received both IPSMs in the prone position.
Parameters of gas exchange, lung mechanics, and hemodynamics as well as pathology
were examined. RESULTS: During the first IPSM, the PLV group showed a significant
increase in PaO2 after instillation of perfluorodecalin (P < .05) and then showed
a dose-dependent increase in PaO2 with PEER. The control and EP groups showed
improvement in PaO2 only at higher PEEP, eventually showing no intergroup
differences at PEEP of 10 cm H2O. During the second IPSM only the PLV group
retained its ability to increase PaO2 to the level obtained during the first IPSM
(P < .05 compared with control and EP groups). During the first IPSM all three
groups showed increasing trend in static compliance (Cst) with PEEP peaking at
PEEP of 8 cm H2O. During the second IPSM, only the PLV group showed increase in
static compliance with PEEP (P < .05 compared with other groups). Lung histology
revealed significantly less hyaline membrane formation in the PLV group (P <
.05). CONCLUSION: PLV shows dose-dependent increase in oxygenation with PEEP and
may reduce lung damage associated with mechanical ventilation.
PMID- 11011824
TI - Effects of milrinone on platelet aggregation in swine with pulmonary
hypertension.
AB - PURPOSE: The purpose of this study was to investigate whether the effect of
milrinone on platelet aggregation was related to the selectivity of vasodilation
vasculature in a swine model with PH. MATERIALS AND METHODS: To induce pulmonary
hypertension, we injected two sets of acid-washed glass beads in 15 swine, which
were divided into two groups (those receiving milrinone or not) and compared with
each other. RESULTS: The induction of pulmonary hypertension decreased the
platelet count and increased the plasma levels of thromboxane B2 and 6-keto
prostaglandin F1alpha. CONCLUSION: A locally high concentration of prostaglandin
I2, at least in part, may produce selectivity of vasodilation in the pulmonary
vasculature.
PMID- 11011825
TI - Measurement of soluble Fas antigen and ligand in circulating serum and intra
abdominal or cerebrospinal fluid during gastrointestinal or cerebrovascular
surgery.
AB - PURPOSE: Soluble Fas antigen (sFas) and ligand (sFasL), which are associated with
apoptosis, have not been evaluated in gastrointestinal or cerebrovascular
surgery. The aim of this study was to measure these substances in serum, intra
abdominal fluid, or cerebrospinal fluid, and to speculate a pathophysiologic role
for Fas-FasL apoptosis in surgery. MATERIALS AND METHODS: Arterial blood and
intraabdominal or cerebrospinal fluid were collected at intervals from 27
gastrointestinal surgical patients, 10 cerebrovascular surgical patients, and 10
spinal anesthesia patients. RESULTS: Serum sFas levels did not change during and
after surgery. Intra-abdominal and cerebrospinal sFas levels were identical to
and lower than those in serum. Serum sFasL levels did not change during surgery,
but decreased after surgery. Intra-abdominal and cerebrospinal sFasL levels were
higher than and identical to those in serum. In spinal anesthesia, cerebrospinal
sFas and sFasL levels were lower than those in serum. CONCLUSIONS: Serum sFasL
decreases after surgery, whereas intra-abdominal or cerebrospinal sFasL
increases, although sFas in each site does not change, suggesting redistribution
of activated lymphocytes into local surgical wounds and induction of apoptosis in
this site.
PMID- 11011826
TI - Personality disorders, history of trauma, and posttraumatic stress disorder in
subjects with anxiety disorders.
AB - The purpose of the study was to examine the association of personality disorders,
history of trauma, and posttraumatic stress disorder (PTSD) in a large sample of
subjects with anxiety disorders. Categorical and continuous indices of
personality disorders were compared in three groups from the Harvard/Brown
Anxiety Disorders Research Project (HARP): subjects with no history of trauma (n
= 403), subjects with a history of trauma but no history of PTSD (n = 151), and
subjects with a current or past diagnosis of PTSD (n = 68). Subjects with PTSD
were more likely to meet criteria for borderline or self-defeating personality
disorder than subjects in the other two groups. PTSD subjects also had higher
scores on the continuous measures (total number of criteria met) for borderline
and self-defeating personality disorder than the other two groups. The findings
suggest that a diagnosis of PTSD rather than a history of trauma is associated
with borderline and self-defeating personality disorder features. Alternative
conceptualizations of axis II features in individuals with PTSD are discussed.
PMID- 11011827
TI - Computerized measurement of cognitive impairment and associated neuropsychiatric
dimensions.
AB - This study aimed to cross-validate the capacity of a computer software program to
detect and measure, using a measurement method applied to the content and form
analysis of 5-minute speech samples, cognitive impairment and associated comorbid
neuropsychiatric psychobiological dimensions in drug-abusing patients. At the
University of California-Irvine (UCI) Neuropsychiatric Center, 28 drug-abusing
inpatients using illegal drugs were clinically evaluated. Their scores for
cognitive impairment derived by the computerized content analysis method were
compared with scores derived from selected tests from the Halstead-Reitan
Neuropsychological Test Battery, the computerized Automated Neuropsychological
Assessment Metric Battery (ANAM), the Alzheimer's Disease Assessment Scale
Cognitive Portion, the Stroop Color and Word Test, the Symbol Digit Modalities
Test, and the Controlled Oral Word Association Test. The statistical significance
(P value) of the correlations of scores from these different measures with scores
obtained from the computerized content analysis measures was less than .05 to
.001. The comparative "hit rate," detecting cognitive impairment above the norms
for each measure administered to these drug-abusing patients, for the
computerized content analysis measures and some of the ANAM neuropsychological
measures was 75% to 89%, and for the other neuropsychological measures, 25% to
64%. In conclusion, the computerized content analysis methodology applied to 5
minute verbal samples is a valid, rapid, easily administered measurement
instrument for assessing the magnitude of cognitive impairment and comorbid
neuropsychiatric dimensions.
PMID- 11011828
TI - Comorbid psychiatric diagnosis and long-term drinking outcome.
AB - This longitudinal study of alcoholics investigated which psychiatric
comorbidities among alcoholics would predict very long-term drinking outcome.
Previous research has yielded inconsistent findings. We hypothesized that
antisocial personality characteristics alone among psychiatric comorbidities
would show an association with poorer drinking outcome. The use of multiple
measures of psychopathology, a relatively large sample size, and an absence of
systematic treatment matching to particular patient groups were all aspects of
the current study which allowed for a comprehensive examination of this issue.
The study used single and multivariate correlational analyses. The setting was an
inpatient Veterans Administration alcohol dependence treatment unit and follow-up
clinic. Participants were 255 adult male veterans diagnosed with alcohol
dependence. The predictors were the Symptom Checklist 90 (SCL), Minnesota
Multiphasic Personality Inventory (MMPI), and Psychiatric Diagnostic Interview
(PDI). The outcome measure was the Clinician Rating of Drinking Scale (CRDS). The
study showed that antisocial personality characteristics alone were consistently
associated with a worse long-term drinking outcome. However, despite the
consistent presence of a statistical association between antisocial personality
characteristics and a poorer long-term drinking outcome, the small size of the
relationship is a very important issue which is discussed in detail.
PMID- 11011829
TI - Bipolar II disorder and comorbidity.
AB - The validity and reliability of the diagnosis of bipolar II disorder has been
questioned by means of comorbidity with nonaffective disorders, including
substance abuse, personality disorders, and anxiety disorders. This study
examined the comorbid diagnosis of a sample of bipolar II patients, comparing
patients with comorbidity and those with "pure" bipolar II disorder. Forty
Research Diagnostic Criteria (RDC) bipolar II patients were assessed by means of
the Schedule for Affective Disorders and Schizophrenia, Lifetime Version (SADS-L)
and Structured Clinical Interview for DSM-III-R axis I (SCID-II) for personality
disorders. Patients fulfilling RDC criteria for any psychiatric disorder (except
personality disorders) or DSM-IV criteria for any personality disorder were
compared with patients without comorbidity. For practical reasons, cyclothymia
was not considered as a comorbid diagnosis. Half of the sample had lifetime
comorbidity with other psychiatric disorders, mainly personality disorders (33%),
substance abuse or dependence (21%), and anxiety disorders (8%). However, only
the rates of suicidal ideation (74% v 24%, chi square [chi2] = 9.03, P = .003)
and suicide attempts (45% v 5%, chi2 = 8.53, P = .003) were significantly
different between patients with and without comorbidity. In summary, although the
rates of comorbidity are relatively high in bipolar II disorder, most clinical
and course variables are strikingly similar in patients with and without
comorbidity except for suicidal behavior, suggesting that comorbidity does not
reduce the validity of the diagnosis of bipolar II disorder.
PMID- 11011830
TI - Psychosocial issues for women with trichotillomania.
AB - Trichotillomania, the compulsive urge to pull out one's hair, is a poorly studied
chronic condition affecting 2 to 8 million people, 90% of whom are women.
Significant gains have been made about the nature and clinical presentation of
this disorder, and yet conceptualizations of trichotillomania remain inconsistent
and controversial. Consequently, treatments for trichotillomania have proven to
be largely ineffective. Anecdotal case studies have provided us with preliminary
data about the impact of this condition on emotional, psychological, and social
well-being. To date, there are no empirical studies that focus on patients'
subjective experiences with their disorder. The purpose of this report is to
identify and discuss the concerns of women with trichotillomania. We have also
provided clinical examples to highlight how these concerns are evident in the
lives of these women. A total of seven women participated in focused interviews
which asked them to reflect on their experiences with compulsive hair pulling.
The interview transcripts were analyzed for themes using techniques from the
constant comparative method. Additionally, women were asked to complete a
demographic self-report. Our analysis identified themes pertinent to negative
affects, control, and triggering precipitants. We argue that identifying and
integrating these themes in current treatment protocols is the first step to
improving the efficacy of treatment for trichotillomania.
PMID- 11011831
TI - Alexithymia, gender, and hemispheric functioning.
AB - It has been hypothesized that alexithymia is related to an impairment of the
right hemisphere or a deficiency in interhemispheric transfer. We used the
Toronto Alexithymia Scale-20 (TAS-20) and the tactile finger localization task of
Zeitlin et al. to test these relationships on nonclinical samples of college men
and women, and also considered the role of short-term memory. Among 47 men, the
TAS-20 facets of difficulty identifying feelings or difficulty describing
feelings were correlated with poorer performance by the right compared with the
left hemisphere in uncrossed trials and poorer interhemispheric transfer of
information on crossed trials; short-term memory was not related. Thus, both
hemispheric hypotheses were supported for men. However, among 58 women,
alexithymia was completely unrelated to either index of hemispheric functioning;
instead, poorer short-term memory (specifically digits backwards) strongly
predicted poorer interhemispheric transfer. We conclude that deficiencies in
right hemisphere function and interhemispheric transfer may contribute to
alexithymia in men, but not in women.
PMID- 11011832
TI - The impact of parental death versus separation from parents on the mental health
of Israeli adolescents.
AB - Early research suggested that the loss of a parent during childhood can lead to
depression and other psychopathology in children and adults. More recent research
has differentiated between loss due to death and separation from parents and has
questioned the link between early parental death and psychopathology. We examined
the hypothesis that separation from parents has a more detrimental effect than
the death of a parent on the mental health of adolescents in the community.
Israeli adolescents (N = 844) with a mean age of 16.7 +/- 1.0 years (mean +/- SD)
participated in this study. Seventy reported that a parent did not live at home
during one of three 5-year periods until they reached the age of 15; 37 reported
the death of a parent and 777 were from intact families. All participants
completed the Brief Symptom Inventory (BSI), General Well Being Schedule (GWB),
Parental Bonding Instrument (PBI), and Perceived Social Support Family/ Friends
Scales (PSS-Fam and PSS-Fr). Adolescents who had experienced separation from
parents had more psychiatric symptoms (BSI), expressed a lower sense of well
being (GWB), experienced less support from their family (PSS-Fam), and felt less
cared for and more controlled by their parents (PBI) compared with those
belonging to intact families. The death of a parent was not associated with
significantly different scores on these variables. When we controlled for
parental bonding (PBI) and perceived social support from family (PSS-Fam), the
differences between the separation group and the intact family group were no
longer significant. The psychological impact of separation from parents involves
a greater risk for psychopathology than the death of a parent. The quality of the
relationship with the parents moderates the negative impact of separation from
them.
PMID- 11011833
TI - Parasuicide, anhedonia, and depression.
AB - Previous research has shown that anhedonia characterizes suicide attempters. The
present study aimed to replicate this finding using the level of depression as a
control. Seventy-three depressed parasuicides, 30 nondepressed parasuicides, and
104 matched controls were assessed on the Revised Physical Anhedonia Scale (PAS).
Consistent with previous studies, depressed parasuicides were significantly more
anhedonic than controls, but nondepressed parasuicides were not significantly
more anhedonic than controls. Moreover, multiple linear regression analysis
showed that the PAS score explained a negligible part of the variance in the
distinction between parasuicides and controls. Anhedonia in parasuicides
constitutes a depressive feature and not a temperamental trait.
PMID- 11011834
TI - Phenotypic differences in early- and late-onset obsessive-compulsive disorder.
AB - Early-onset forms of many medical diseases have been associated with specific
genetic anomalies. To assess the potential marker value of onset age in obsessive
compulsive disorder (OCD), we examined and compared the phenotypic
characteristics of patients with early and later onset. The study sample included
38 children with DSM-IV OCD and 129 adults 19 years of age or older, 77 of whom
reported OCD onset prior to age 18 and 52 of whom reported OCD onset at 18 years
of age or older. DSM-IV diagnoses were ascertained for all subjects using an
amended version of the Diagnostic Interview for Genetic Studies (DIGS). An
initial comparison of children and adults with childhood onset revealed several
differences, including an earlier onset of clinically significant symptoms
without impairment and earlier onset of DSM-IV OCD, a higher frequency of
learning disabilities, and fewer obsessions and compulsions among our child
patients. For this reason, subsequent analyses included only adult patients with
early and later OCD onset. Nonimpairing symptom onset prior to puberty, a
relatively aggressive course, and a greater number of obsessions and compulsions
unrelated to the amount of time in illness characterized early-onset OCD. Later
onset OCD was characterized by nonimpairing symptom onset during puberty, a
static course, and relatively few obsessions and compulsions that were variably
related to the amount of time in illness. We conclude that children with OCD and
adults with childhood onset differ in their report of clinical characteristics
and should be analyzed separately in studies concerning the phenotypic
characteristics of OCD. Early- and late-onset forms of OCD appear to be
characterized by phenotypic features that have important neurobiologic and
perhaps genetic implications.
PMID- 11011835
TI - Association between cerebral structural abnormalities and dermatoglyphic ridge
counts in schizophrenia.
AB - Dermatoglyphic ridge counts (1) reflect ontogenic processes during the second
trimester of pregnancy and (2) can be influenced by some of the factors that also
affect cerebral development. Therefore, the demonstration of an association
between dermatoglyphic and cerebral structural measures in patients with
schizophrenia would give credence to the view that the structural brain
abnormalities associated with this disorder have their origin early in
development. Twenty-eight male subjects with schizophrenia and 19 male controls
underwent magnetic resonance imaging (MRI) and dermatoglyphic analysis. The
pattern of association between the ab-ridge count and nine MRI features was
dissimilar in cases and controls for two measures. Associations between
dermatoglyphic features, on the one hand, and the frontal CSF (r = .54, P = .004)
and fourth ventricular volume (r = .38, P = .05), on the other, were larger in
the cases versus the controls (test for interaction, P = .08 and P = .06,
respectively). These findings, while in need of replication, support the view
that the cerebral structural abnormalities found in patients with schizophrenia
are the result of an early pathologic process affecting the development of fetal
ectodermal structures.
PMID- 11011836
TI - Impaired Wisconsin card sorting test performance in first-episode schizophrenia:
resource or motivation deficit?
AB - Patients with first-episode schizophrenia (n = 27) and age- and education-matched
healthy controls (n = 27) were administered the standard version of the Wisconsin
Card Sorting Test (WCST), the Wechsler Adult Intelligence Scale-Revised (WAIS-R),
and the Rorschach according to the Comprehensive System (CS). Schizophrenic
patients achieved a significantly lower full-scale IQ and made more perseverative
responses and achieved fewer categories on the WCST than the healthy control
group. No significant associations were observed between effort or motivation and
WCST performance. Schizophrenic patients who made more perseverative responses
tended to be impoverished in terms of available resources, and functioned in a
simplistic way when attending to details of the stimulus field. First-episode
schizophrenics are able to generate motives and initiate goal-directed activity,
but some of them fail to achieve their goals because the cognitive abilities and
available resources required for effective planning, purposeful action, or
effective performance are impaired.
PMID- 11011837
TI - Expressed emotion and family distress in relatives of patients with schizophrenia
in Japan.
AB - We evaluated the association between distress and expressed emotion (EE) in
family members of patients with schizophrenia by the General Health Questionnaire
(GHQ), the Camberwell Family Interview (CFI), and the Five-Minute Speech Sample
(FMSS). The GHQ score was higher in the high-EE group determined by both the CFI
and FMSS. The difference in the GHQ score between high-EE and low-EE groups was
more marked for the CFI. Family distress is closely associated with the EE
classification, but the EE classification by the CFI more markedly reflected
family distress versus the FMSS. Even in relatives with low EE, distress was
marked, and therefore, coping with mental health in family members is important.
PMID- 11011838
TI - Depressive disorders in teenage-onset anorexia nervosa: a controlled
longitudinal, partly community-based study.
AB - The study objective was to examine the prevalence and course of depressive
disorders (DDs) in teenage-onset anorexia nervosa (AN) over a period of 10 years.
Fifty-one adolescents with AN and a sex- and age-matched control group (n = 51)
were assessed at ages 16, 21, and 24 years. Probands and controls were examined
in depth using semistructured and structured interviews. Their parents were
interviewed on the occasion of the first examination. DDs were assessed using DSM
III-R criteria. Subjects with AN had a greatly increased rate of DDs (85%) of all
kinds and at all ages as compared with control subjects. The risk of DD during
the follow-up period from 21 up to and including 24 years could be predicted by
diagnostic group status and the presence of DD during the period from 16 to 21
years, while the risk of DD during the follow-up period from 16 up to and
including 21 years was solely predicted by the presence of AN at age 16 years.
Long-term resolution of the eating disorder (ED) was associated with the absence
of mood disorder or vice versa. Bipolar disorder (BP) occurred at roughly the
expected rate (11%) among subjects (probands and controls) with major depression
(MDD). In conclusion, depression is a very common comorbid problem in AN: more
than four of five individuals with teenage-onset AN had at least one episode of
DSM-III-R depression (MD or dysthymia [DT]) within 10 years after onset of the
ED. AN appears to trigger the first episode of depression, but once it is
manifest, depression predicts further depressive episodes.
PMID- 11011839
TI - Pathways and regulation of homocysteine metabolism in mammals.
AB - Two intersecting pathways, the methionine cycle and the transsulfuration
sequence, compose the mechanisms for homocysteine metabolism in mammals. The
methionine cycle occurs in all tissues and provides for the remethylation of
homocysteine, which conserves methionine. In addition, the cycle is essential for
the recycling of methyltetrahydrofolate. The synthesis of cystathionine is the
first reaction in the irreversible pathway for the catabolism of homocysteine by
means of the sequential conversion to cysteine and sulfate. This pathway has a
limited distribution and is found primarily in the liver, kidney, small intestine
and pancreas. Regulation of homocysteine metabolism is achieved by changes in the
quantity of homocysteine distributed between the two competing pathways. Two
mechanisms are basic to the regulatory process. Changes in tissue content of the
relevant enzymes are the response to sustained perturbations. The inherent
kinetic properties of the enzymes provide an immediate response to alterations in
the tissue concentrations of substrates and other metabolic effectors. S
adenosylmethionine, S-adenosylhomocysteine, and methyltetrahydrofolate are of
particular importance in that context.
PMID- 11011840
TI - Consequences of homocysteine export and oxidation in the vascular system.
AB - The risk for arteriosclerosis and thrombosis of patients with severe
hyperhomocysteinemia is reduced by homocysteine-lowering therapy. Whether this is
the case in patients with mild hyperhomocysteinemia remains to be proved. Another
challenge for researchers is to establish a satisfying pathological mechanism of
the vasotoxicity of a disturbed homocysteine metabolism. Unfortunately, most in
vitro studies use physiologically irrelevant concentrations or forms, or both, of
homocysteine. The role of the different oxidized and reduced forms of
homocysteine in its metabolism has gained little attention. In the cell,
homocysteine is mainly present in its reduced form. In this article export of
homocysteine out of the cell is reported to be regulated by a "reduced
homocysteine carrier." In vitro endothelial cells export homocysteine at a
constant rate in a folate dose-dependent matter. Even at high-normal folate
levels, endothelial cells export homocysteine. As soon as homocysteine is
exported out of the cell, it will be oxidized to a disulfide with any compound
containing a thiol function or undergo a disulfide exchange reaction, both
resulting in formation of disulfides of homocysteine. Consequently, in plasma,
about 99% of homocysteine is bound to disulfides. Before homocysteine can be
metabolized, it needs to be taken up by the cell via carriers, channels, or
receptors recognizing the different homocysteine disulfides. In the cell, the
homocysteine disulfides are reduced, liberating homocysteine in its reduced form.
Next, homocysteine can be metabolized after binding to the homocysteine
converting enzymes. In particular, the liver and kidney supposedly take up and
metabolize significant amounts of homocysteine.
PMID- 11011841
TI - Assay methods for the measurement of total homocyst(e)ine in plasma.
AB - Analytical methods to measure plasma total homocyst(e)ine (tHcy) concentrations
are reviewed. High-pressure liquid chromatography (HPLC) with fluorometric
detection is the most widely used method to determine plasma tHcy concentrations.
Both monobromobimane and ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate
(SBD-F) are popular thiol-specific fluorogenic agents suitable for tHcy analysis.
Monobromobimane has the advantage that it is highly reactive towards thiols, but
its hydrolysis products are also fluorogenic, thus necessitating complex
chromatography to obtain satisfactory separation between the compounds of
interest and interferents. SBD-F does not show fluorescence, thus allowing
isocratic separation of SBD-F derivatized thiols. SBD-thiol adducts are light
sensitive and require protection against light to ensure reliable results. HPLC
with electrochemical detection is also often used and has the advantage that no
derivatization of thiols is required prior to detection. A recently reported
liquid chromatography electrospray tandem mass spectrometric assay has the
potential to become the reference method for plasma tHcy analysis. Other methods
to measure plasma tHcy concentrations include gas-liquid chromatography,
capillary electrophoresis, and immunoassays. Fluorescence polarization
immunoassay compares well with gas chromatography-mass spectrometry and may
become the method of choice in routine diagnostic clinical chemistry
laboratories. Instability of tHcy in whole blood as well as postprandial and
orthostatic variation are preanalytical factors that should be accounted for in
plasma tHcy analysis. Between-method and between-laboratory variations in serum
tHcy analysis are not yet satisfactory; certified reference material and
standardization of the plasma tHcy assay will be essential to reduce between
laboratory bias.
PMID- 11011842
TI - Homocysteine, coagulation, platelet function, and thrombosis.
AB - Over the last 30 years, a growing body of evidence has documented the role of
hyperhomocysteinemia (HHcy) as an independent vascular risk factor. However, the
mechanisms through which elevated circulating levels of homocysteine (Hcy) cause
vascular injury and promote thrombosis remain elusive. Most findings have been
achieved in in vitro studies employing exceedingly high concentrations of Hcy,
whereas only a few studies have been carried out in vivo in humans. In
homocystinuric patients, homozygotes for mutations of the gene coding for the
cystathionine beta-synthase enzyme, abnormalities of coagulation variables
reflecting a hypercoagulable state, have been reported. In vitro studies provide
a biochemical background for such a state. In homocystinuric patients, an in vivo
platelet activation has also been reported. The latter abnormality is not
corrected by the bolus infusion of concentrations of hirudin, which determines a
long-lasting impairment of the conversion of fibrinogen to fibrin by thrombin; in
contrast, it appears at least in part lowered by the administration of the
antioxidant drug probucol. During the autooxidation of Hcy in plasma, reactive
oxygen species are generated. The latter initiate lipid peroxidation in cell
membranes (potentially responsible for endothelial dysfunction) and in
circulating lipoproteins. Oxidized low-density lipoproteins (LDL) may trigger
platelet activation as well as some of the hemostatic abnormalities reported in
such patients. Thus the oxidative stress induced by Hcy may be a key process in
the pathogenesis of thrombosis in HHcy. Accumulation of adenosylhomocysteine in
cells (a consequence of high circulating levels of homocysteine) inhibits
methyltransferase enzymes, in turn preventing repair of aged or damaged cells.
This mechanism has been recently documented in patients with renal failure and
HHcy and provides an additional direction to be followed to understand the
tendency to thrombosis in moderate HHcy.
PMID- 11011843
TI - Genetic modulation of homocysteinemia.
AB - With the identification of hyperhomocysteinemia as a risk factor for
cardiovascular disease, an understanding of the genetic determinants of plasma
homocysteine is important for prevention and treatment. It has been known for
some time that homocystinuria, a rare inborn error of metabolism, can be due to
genetic mutations that severely disrupt homocysteine metabolism. A more recent
development is the finding that milder, but more common, genetic mutations in the
same enzymes might also contribute to an elevation in plasma homocysteine. The
best example of this concept is a missense mutation (alanine to valine) at base
pair (bp) 677 of methylenetetrahydrofolate reductase (MTHFR), the enzyme that
provides the folate derivative for conversion of homocysteine to methionine. This
mutation results in mild hyperhomocysteinemia, primarily when folate levels are
low, providing a rationale (folate supplementation) for overcoming the genetic
deficiency. Additional genetic variants in MTHFR and in other enzymes of
homocysteine metabolism are being identified as the cDNAs/genes become isolated.
These variants include a glutamate to alanine mutation (bp 1298) in MTHFR, an
aspartate to glycine mutation (bp 2756) in methionine synthase, and an isoleucine
to methionine mutation (bp 66) in methionine synthase reductase. These variants
have been identified relatively recently; therefore additional investigations are
required to determine their clinical significance with respect to mild
hyperhomocysteinemia and vascular disease.
PMID- 11011844
TI - Biological and environmental determinants of plasma homocysteine.
AB - This article gives an overview over common physiological, lifestyle, and
pathological conditions that may modulate the homocysteine status. The interplay
of several environmental factors, including age, gender, nutrition, smoking, and
coffee consumption and physical activity with commonly used drugs and prevalent
diseases are described. In most cases, an abnormal homocysteine status is not
caused by a single factor alone but often is the result of combined effects. We
address these frequently found "clusters" of homocysteine-modulating factors.
Finally, we give an overview of likely causes of hyperhomocysteinemia found in an
authentic material. This material is based on 2462 routine measurements of plasma
total homocysteine carried out at the Haukeland University Hospital. The data
represent the total number of combined homocysteine and methylmalonic acid
determinations, requested by general practitioners in Norway during February
1998.
PMID- 11011845
TI - Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction.
AB - Hyperhomocysteinemia has been associated with premature atherothrombotic vascular
disease. It is not known whether hyperhomocysteinemia induces a distinct type of
vascular disease. Its interaction, if any, with traditional risk factors also
remains unclear. The pathophysiological mechanisms linking hyperhomocysteinemia
to vascular disease have been extensively studied in vitro and in animals. From
these studies, it has been suggested that homocysteine limits the bioavailability
of nitric oxide (NO), increases oxidative stress, stimulates smooth cell
proliferation, and alters elastic wall properties. The relevance of these
proposed mechanisms in vivo is unclear, because clinical studies have yielded
controversial results with regard to the relation between plasma homocysteine
levels and indices of endothelial function, such as brachial artery flow-mediated
vasodilatation and plasma levels of endothelium-derived marker proteins. Up till
now, there have been no controlled data on the effects of homocysteine-lowering
treatment on vascular function or clinical end points. The precise mechanisms (if
any) by which homocysteine mediates its adverse vascular effects are in fact
unknown but may relate to impaired endothelial and smooth muscle cell function.
PMID- 11011846
TI - Mild hyperhomocysteinemia is an independent risk factor of arterial vascular
disease.
AB - Evidence of a positive association between mild hyperhomocysteinemia and arterial
vascular disease has been accumulating in the last decade. Mild
hyperhomocysteinemia acts as an independent vascular risk factor with equal
strength as hypercholesterolemia and smoking. If jointly present with
hypertension and smoking, its effect seems synergistic. This could make the
outcome of homocysteine-lowering intervention beneficial, particularly in cases
with concomitance of conventional vascular risk factors. So far, however, data on
the clinical outcome of homocysteine-lowering treatment with a simple, safe, and
cheap vitamin regimen are lacking. Trials investigating a beneficial clinical
effect of homocysteine-lowering treatment using folic acid in a dose ranging from
0.2 to 5 mg daily, alone or in combination with vitamin B12 with or without
vitamin B6 versus placebo, are ongoing. Furthermore, exploration of the unifying
mechanism by which increased homocysteine levels may lead to both arterial and
venous occlusions is warranted. These lines of investigations have to provide the
ultimate proof of causality of hyperhomocysteinemia in vascular disease in the
near future.
PMID- 11011847
TI - Homocysteine and venous thrombosis: outline of a vitamin intervention trial.
AB - In the past years several case-control studies established the association of an
elevated plasma homocysteine concentration and the risk of venous
thromboembolism. It is still unclear if elevated homocysteine concentrations can
cause venous thrombosis. The VITRO (VItamins and ThROmbosis) trial is the first
multicenter, randomized, double-blind and placebo-controlled study to evaluate
the effect of homocysteine-lowering therapy by means of 5 mg folic acid, 0.4 mg
vitamin B12 and 50 mg vitamin B6. The study is a secondary prevention trial in
600 patients who suffered from a first episode of idiopathic deep vein thrombosis
(DVT) or pulmonary embolism (PE), or both. There will be 300 hyperhomocysteinemic
and 300 normohomocysteinemic patients included, all with an objectivated venous
thrombosis. The end point is recurrence of venous thrombosis.
PMID- 11011848
TI - Interaction between hyperhomocysteinemia and inherited thrombophilic factors in
venous thromboembolism.
AB - Hyperhomocysteinemia is an established risk factor for deep vein thrombosis.
Factor V Leiden has been reported to potentiate the thrombotic risk related with
severe hyperhomocysteinemia, being more represented in thrombotic patients with
homocystinuria as compared with patients without a history of thrombosis. The
results concerning the interaction between moderate hyperhomocysteinemia and
inherited thrombophilic factors such as Factor V Leiden or the prothrombin
G20210A mutation are contradictory. The relative risk for venous thrombosis has
been reported to be increased 10- to 50-fold in patients carrying both
hyperhomocysteinemia and inherited thrombophilia in comparison with normal
controls, suggesting a synergistic interaction, yet other studies failed to
confirm such conclusion. The heterogeneity of these findings is in part due to
the small number of individuals with double defects, leading to statistically
unreliable results. Genotyping for mutations that are possible causes of moderate
hyperhomocysteinemia, such as the thermolabile variant (C677T) of
methylenetetrahydrofolate reductase (MTHFR), does not seem useful to identify
individuals at higher risk for venous thromboembolism. In fact, in most of the
studies the presence of the C677T MTHFR homozygous genotype does not increase the
thrombotic risk associated with Factor V Leiden or the prothrombin mutation.
PMID- 11011849
TI - Homocysteine and renal disease.
AB - Hyperhomocysteinemia refers to an elevated circulating level of the sulfur
containing amino acid homocysteine and has been shown to be a risk factor for
vascular disease in the general population. In patients with renal failure,
hyperhomocysteinemia is a common feature. The underlying pathophysiological
mechanism for this phenomenon is unknown. Proposed mechanisms include reduced
renal elimination of homocysteine and impaired nonrenal disposal, possibly
because of inhibition of crucial enzymes in the methionine-homocysteine
metabolism by the uremic milieu. Absolute or relative deficiencies of folate,
vitamin B6, or vitamin B12 may also play a role. Several case-control and
prospective studies have now indicated that hyperhomocystenemia is an independent
risk factor for atherothrombotic disease in patients with predialysis and end
stage renal disease. In renal patients, plasma homocysteine concentration can be
reduced by administration of folic acid in doses ranging from 1 to 15 mg per day.
In more than 50% of the cases, however, the homocysteine concentration remains
above 15 micromol/L. The effects of vitamin B12 or vitamin B6 are unclear. Large
intervention trials are now needed to establish whether homocysteine-lowering
therapy will reduce atherothrombotic events in patients with renal failure. These
studies are now planned or are ongoing.
PMID- 11011850
TI - Hyperhomocysteinemia and risk of vascular disease in women.
AB - Plasma levels of total homocysteine (tHcy), a possible risk factor for vascular
disease, are generally lower in women than in men and lower in premenopausal
women than in postmenopausal women. This article reviews studies that have
investigated associations of hyperhomocysteinemia with risk of vascular disease
among women or that compared risk by stratum of gender or menopausal status.
Seven out of 12 epidemiological studies that included both men and women found
hyperhomocysteinemia to be a stronger risk factor in women than in men. However,
the interaction effect was statistically significant for only 1 study. Three
studies observed no risk difference between men and women, and 2 observed a
weaker association in women. In addition, 3 studies that consisted (almost)
entirely of women observed direct associations of hyperhomocysteinemia with
vascular disease risk, comparable to associations observed in male populations.
Hyperhomocysteinemia was associated with increased risk in populations of both
young and elderly women, but only few studies have compared risks among
premenopausal and postmenopausal women. However, the limited data indicate that
hyperhomocysteinemia is also associated with elevation of vascular disease risk
before the menopause. The stronger association among women in some studies may be
explained by aspects of the study design, such as age at inclusion (i.e., women
usually suffer from vascular diseases later in life than do men), or aspects of
the data analysis, such as use of an overall instead of a gender-specific cutoff
point. Of course, one cannot exclude the possibility that women are somehow more
susceptible to detrimental effects of tHcy than men are, although there is
evidence from other studies that estrogens have a "protective" effect on the
vascular wall and a favorable effect on hemostasis. In conclusion, we should
consider hyperhomocysteinemia as a potential risk factor for vascular disease in
both men and women, before and after the menopause.
PMID- 11011851
TI - Vascular complications of severe hyperhomocysteinemia in patients with
homocystinuria due to cystathionine beta-synthase deficiency: effects of
homocysteine-lowering therapy.
AB - Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency leads to
severe hyperhomocysteinemia (HHcy). Vascular events (VE) remain the major cause
of morbidity and mortality in the untreated patients with HCU. The study on the
natural history of untreated HCU disclosed that, at the time of maximal risk, in
other words beyond 10 years old, there was one event per 25 years. Recent studies
from Australia (n = 32), The Netherlands (n = 28), and Ireland (n = 24) have
documented the effects of long-term treatment on the vascular outcome of a total
of 84 patients with 1314 patient-years of treatment for HCU. The mean (range) age
was 27.8 (2.5 to 70) years. Five VE were recorded during treatment; one pulmonary
embolism, two myocardial infarctions, and two abdominal aneurysms. All five VE
occurred in B6-responsive patients at a mean (range) age of 48.8 (30 to 60)
years. In 1314 patient-years of treatment, 53 VE would have been expected if they
remained untreated; instead only 5 were documented, relative risk = 0.091 (95%
confidence interval [CI] 0.043 to 0.190; p < 0.001). Appropriate homocysteine
lowering therapy for severe HHcy significantly reduced the vascular risk in
patients with HCU. VE were rare with treatment despite the fact that the post
treatment homocysteine levels were several times higher than the cutoff point for
homocysteine in the normal population. The present findings may have relevance to
the current concept of "mild HHcy" as a risk factor for vascular disease, with
elevated plasma homocysteine levels considerably lower than that of the post
treatment levels in this group of reported patients.
PMID- 11011853
TI - Fortifying food with folic acid.
AB - Folic acid supplementation may help prevent the following three common and
important disorders: neural tube defect pregnancies, ischemic heart disease and
strokes, and possibly colon cancer. Several studies have irrefutably established
that folic acid supplementation in proper doses reduces neural tube defect
pregnancies. Fortified food would be the most reliable way to address this health
issue. Several epidemiologic reports have established a close link between
hyperhomocysteinemia and ischemic heart disease. This is supported by evidence
obtained from genetic defects leading to elevated plasma levels of homocysteine.
There is reasonable evidence to conclude that hyperhomocysteinemia is the actual
cause of excessive cardiac diseases. Again, folic acid supplementation in proper
doses could potentially reduce ischemic heart disease by 40% There is also some
evidence to suggest that folic acid treatment reduces the incidence of colon
cancer. The reduction in all three health problems is dependent upon the dose of
folic acid administered. The levels needed are rarely supplied by the daily food
intake, even under ideal conditions, although breakfast cereals address this
problem at least in part. It is proposed that flour be fortified because it is a
food product heavily used by most people, and that governmental agencies should
oversee such programs because they are responsible for setting public health
policies.
PMID- 11011852
TI - Vitamin supplements and cardiovascular risk: review of the randomized trials of
homocysteine-lowering vitamin supplements.
AB - Epidemiological studies have shown that higher blood homocysteine levels appear
to be associated with higher risks of coronary, cerebral, and peripheral vascular
disease and are inversely related to blood levels of folate and of vitamin B12
and vitamin B6. However, observational studies cannot exclude the possibility
that elevated homocysteine levels may be associated with some other factor,
rather than being causally related to vascular disease. Large-scale clinical
trials of sufficient dose and duration of treatment are required to test this
hypothesis, but there was substantial uncertainty about the optimal vitamin
regimen to test in such trials. A meta-analysis of 12 randomized trials of
vitamin supplements to lower homocysteine levels was carried out to determine the
optimal dose of folic acid required to lower homocysteine levels and to assess
whether vitamin B12 or vitamin B6 had additive effects. This meta-analysis
demonstrated that reductions in blood homocysteine levels were greater at higher
pretreatment blood homocysteine levels and at lower pretreatment folate
concentrations. After standardization for a pretreatment homocysteine
concentration of 12 micromol/L and folate concentration of 12 nmol/L (approximate
average concentrations for western populations), dietary folic acid reduced
homocysteine levels by 25% (95% confidence interval [CI]: 23 to 28%) with similar
effects in a daily dosage range of 0.5 to 5 mg. Vitamin B12 (mean 0.5 mg)
produced an additional reduction in blood homocysteine of 7%, whereas vitamin B6
(mean 16.5 mg) did not have any significant effect. Hence, in typical
populations, daily supplementation with both 0.5 to 5 mg folic acid and about 0.5
mg vitamin B12 would be expected to reduce homocysteine levels by one quarter to
one third (from about 12 micromol/L to about 8 to 9 micromol/L). Large-scale
randomized trials of such regimens are now required to determine whether lowering
homocysteine levels by folic acid and vitamin B12, with or without added vitamin
B6, reduces the risk of vascular disease.
PMID- 11011854
TI - New international network will study HIV prevention.
PMID- 11011855
TI - Dermatofibrosarcoma protuberans: early recognition and treatment.
PMID- 11011856
TI - Possible ticlopidine-induced cholestatic jaundice.
PMID- 11011857
TI - Vacuum extraction: a necessary skill.
PMID- 11011858
TI - Weighing the evidence for vitamin supplementation and CVD prevention.
PMID- 11011859
TI - Sickle cell disease in childhood: Part II. Diagnosis and treatment of major
complications and recent advances in treatment.
AB - Treatment advances over the past 25 years have significantly decreased morbidity
and mortality in children with sickle cell disease. Aggressive management of
fever, early diagnosis of acute chest syndrome, judicious use of transfusions and
proper treatment of pain can improve quality of life and prognosis for these
children. Prophylactic hydroxyurea therapy has been shown to reduce the incidence
and severity of pain crises in adults with sickle cell disease and has been
effective in limited studies conducted in children. Research into stem cell
transplantation provides hope that a cure for sickle cell disease may be
possible.
PMID- 11011860
TI - Assisted vaginal delivery using the vacuum extractor.
AB - Vacuum extractors have replaced forceps for many situations in which assistance
is required to achieve vaginal delivery. Compared with metal-cup vacuum
extractors, soft-cup devices are easier to use and cause fewer neonatal scalp
injuries; however, they detach more frequently. Vacuum extractors can cause
neonatal injury. These devices should be employed when indicated, usually for a
nonreassuring fetal heart tracing or failure to progress in the second stage of
labor. Complications may be minimized if the physician recognizes
contraindications to the use of vacuum extraction. Complete documentation is
essential.
PMID- 11011861
TI - Alternative therapies: Part II. Congestive heart failure and
hypercholesterolemia.
AB - Natural supplements are widely used by the American public but, while claims of
their therapeutic effects abound, medical research does not always support their
effectiveness. Clinical trials using Q10 for the management of congestive heart
failure have had conflicting results; hawthorn is prescribed in Germany for the
treatment of this condition, but no trials have been conducted in the United
States. Although initial research about the use of garlic in the management of
hypercholesterolemia was encouraging, follow-up studies have failed to verify
these results. Substituting soy protein for high-fat animal protein diets,
however, does have a beneficial effect on serum lipid levels. So far, cholestin
(a natural product containing several statins) has proved to be a cost-saving
lipid-lowering medication, and fenugreek may offer modest improvement as well.
Gugulipid is also promising but requires further research.
PMID- 11011862
TI - Proteinuria in adults: a diagnostic approach.
AB - Proteinuria is a common finding in adults in primary care practice. An
algorithmic approach can be used to differentiate benign causes of proteinuria
from rarer, more serious disorders. Benign causes include fever, intense activity
or exercise, dehydration, emotional stress and acute illness. More serious causes
include glomerulonephritis and multiple myeloma. Alkaline, dilute or concentrated
urine; gross hematuria; and the presence of mucus, semen or white blood cells can
cause a dipstick urinalysis to be falsely positive for protein. Of the three
pathophysiologic mechanisms (glomerular, tubular and overflow) that produce
proteinuria, glomerular malfunction is the most common and usually corresponds to
a urinary protein excretion of more than 2 g per 24 hours. When a quantitative
measurement of urinary protein is needed, most physicians prefer a 24-hour urine
specimen. However, the urine protein-to-creatinine ratio performed on a random
specimen has many advantages over the 24-hour collection, primarily convenience
and possibly accuracy. Most patients evaluated for proteinuria have a benign
cause. Patients with proteinuria greater than 2 g per day or in whom the
underlying etiology remains unclear after a thorough medical evaluation should be
referred to a nephrologist.
PMID- 11011863
TI - Management of bipolar disorder.
AB - Bipolar disorder most commonly is diagnosed in persons between 18 and 24 years of
age. The clinical presentations of this disorder are broad and include mania,
hypomania and psychosis. Frequently associated comorbid conditions include
substance abuse and anxiety disorders. Patients with acute mania must be
evaluated urgently. Effective mood stabilizers include lithium, valproic acid and
carbamazepine. A comprehensive management program, including collaboration
between the patient's family physician and psychiatrist, should be implemented to
optimize medical care.
PMID- 11011864
TI - Update on vitamin supplements for the prevention of coronary disease and stroke.
AB - Dietary antioxidants and folic acid may play a role in the pathophysiology of
coronary disease and stroke. We review patient-oriented evidence on the
effectiveness of supplementation with antioxidants and/or folic acid in the
prevention of myocardial infarction and stroke. Observational data suggest
cardiovascular benefit of vitamin E supplementation, but results of controlled
clinical trials are inconsistent regarding the effect on nonfatal myocardial
infarction. Moreover, studies have not shown a protective effect of vitamin E
against fatal myocardial infarction and have not addressed stroke. For vitamin C
and folic acid supplementation, observational data are inconsistent and
controlled clinical trials are lacking. Thus, the available evidence is
insufficient to recommend the routine use of vitamin E, vitamin C or folate
supplements for the prevention of myocardial infarction or stroke. The evidence
argues against the use of beta carotene supplements for this purpose. The costs
and risks associated with these supplements are low, however, and physicians may
choose to recommend vitamin E, folate and/or vitamin C supplementation pending
conclusive evidence from clinical trials.
PMID- 11011865
TI - ACOG issues recommendations for the management of endometriosis. American College
of Obstetricians and Gynecologists.
PMID- 11011866
TI - Spatial stimulus-response compatibility and coding of tactile motor events:
influence of distance between stimulated and responding body parts, spatial
complexity of the task and sex of subject.
AB - We studied spatial stimulus response compatibility in the somatosensory modality
by instructing 16 men and 16 women to press a key using the left or the right
thumb in response to a nonnoxious electric stimulation delivered either to the
left or to the right little finger or, in different blocks, to the left or to the
right malleolar region. The task was performed in compatible (stimulus and key
response on the same side of the corporeal midline) and in incompatible
conditions (stimulus and key-response on opposite sides of the corporeal
midline). In Exp. 1 subjects were tested while keeping their limbs in anatomic
position; in Exp. 2 subjects performed the task while keeping the left upper and
lower limbs on the right side and the right limbs on the left side of the bodily
midline (crossed position). The compatibility effect was observed in both
experiments and was higher for stimuli delivered to the little finger than to the
malleolar region. This suggests that the cost of inhibiting compatible responses
is maximal when stimulated and responding body parts are contiguous. Moreover, in
the spatially most demanding task (Exp. 2) men outperformed women for both speed
and accuracy suggesting a sex related specialisation in the spatial processing of
somatosensory information.
PMID- 11011867
TI - Laser-induced afterimages in humans.
AB - Afterimages induced by incoherent light sources have been studied as complex
visual perceptions for over 200 years; however, individuals who have viewed a
coherent source (a laser) on-axis have reported visual experiences unlike those
observed for full-field flashes from incoherent sources. In the present study, 10
volunteers viewed all combinations of blue, green, and red laser light and
background colors that matched the wavelengths of the laser sources (a total of 9
conditions). The bright focal (50 microm retinal irradiance diameter) 3-sec.
exposures (approximately 9 log trolands-40% of the maximum permissible exposure
level) given to the volunteers were administered as they performed a simulator
tracking task. A 50/50 mirror (a mirror which reflected 50% of the laser beam
into the optical pathway while allowing the 50% of the light from the visual
scene to pass through the mirror) permitted simultaneous intrabeam viewing of the
laser source and the scene. The volunteers were asked to report what they saw
immediately after the laser was turned off and 1-min postexposure. The immediate
reports indicated that the image they observed was the same color as the laser
source and not the complementary color. Also, the images were of ten surrounded
by well-defined borders and, regardless of laser's or background's col or, were
generally red. One minute following presentation of the laser light the images
seen were predominantly purple, dark or no longer present; however, the edge
color when present generally appeared red. The immediate appearance of the images
was inferred to be neural in nature and not photochemical. These results suggest
the properties of the laser source, i.e., coherency, monochromaticity, and the
laser's capacity to place an intense beam of light in a small retinal area, all
contributed to the unique appearance of the postflash images.
PMID- 11011868
TI - Topology and mental processes.
AB - The study reported here considers the effect of rotation on the decision time
taken to compare nonrigid objects, presented as like and unlike pairs of knots
and unknots. The results for 48 subjects, 21 to 45 years old, support the notion
that images which have a characteristic 'foundation part' are more easily stored
and accessed in the brain. Also, there is evidence that the comparison of
deformable objects is processed by mental strategies other than self-evident
mental rotation.
PMID- 11011869
TI - Coincidence timing of a soccer pass: effects of stimulus velocity and movement
distance.
AB - The effect of stimulus velocity and movement extent on coincidence timing and
spatial accuracy of a soccer pass was investigated. A Bassin anticipation timer
provided light stimulus velocities of 1.79 or 2.68 m/sec. (designated as "Low"
and "High", respectively), and subjects were required to kick a stationary soccer
ball so that it struck a target in coincidence with the arrival of the light
stimulus at the end of the runway. Two kick types were used. The "Short"
condition began with the subject 70 cm from the ball and required a single
forward step with the nonkicking leg before making the kick. The "Long" condition
began 140 cm from the ball and required two steps before the kick. Twenty male
subjects were given 16 trials under each of the four combinations of stimulus
velocity and kick type. The expectation that the faster stimulus velocity would
be associated with lower coincidence timing scores for both absolute error (AE)
and variable error (VE) and with late responding for constant error (CEO) was
upheld with the exception that for the Long Kick-High Velocity condition, AE was
highest. The index of preprogramming (IP) was used to test the hypothesis that a
two-stage control process would characterise coincidence anticipation performance
involving whole-body movements. Results showed that the preparatory phase of
responding produced zero-order IPs signifying reliance on feedback control. Also,
while the striking phase produced high IP and suggested reliance on preprogrammed
control, the possibility that the High Velocity conditions may have limited the
responses was recognised. As a consequence, the role of open-loop processes
remained equivocal. The findings are, however, in agreement with the view that
the sensorimotor and movement-execution phases of responding require a process
that is characterised by adaptability to regulatory features of the environment
via closed loop mechanisms involving perception-action coupling.
PMID- 11011870
TI - The dominant ear.
AB - Presented are some aspects of the dominant ear or earedness which are also
important for other lateralities. Earedness refers not only to a sensory but also
to a motor phenomenon.
PMID- 11011871
TI - Comparison of health promotion and deterrent prompts in increasing use of stairs
over escalators.
AB - This study compared the effectiveness of two point-of-decision prompts within the
same environmental setting. The effects of a health promotion sign were compared
with activity change resulting from a deterrent sign. Individuals were observed
using the upward stairs or upward escalator at a midwest regional air port during
a 5-week period in which intervention signs were compared with no sign conditions
on activity choice. During Weeks 1, 3, and 5 behaviors were assessed without any
prompts. During Week 2, a health promotion sign was posted at the behavioral
choice point which read "Keep your heart healthy, use the stairs." During Week 4,
a deterrent sign which read "Please limit escalator use to staff and those unable
to use the stairs" was posted at the same behavioral choice point. Younger (<40)
women (14.8%) and men (10.8%) used the stairs more frequently, followed by older
women (9.3%) and older men (6.9%). A hierarchical log linear analysis showed that
stair use increased during both interventions, which was significantly moderated
by age. Point-of-decision prompts appear to be effective environmental
interventions for promoting increases in physical activity.
PMID- 11011872
TI - Satisfaction with life scale: analysis of factorial invariance for adolescents
and elderly persons.
AB - The purpose of this work is to analyze the factorial invariance of the
Satisfaction With Life Scale across samples of adolescents and elderly persons.
Data from 266 subjects were analyzed. Half were Spanish junior high-school
students (65 girls and 68 boys) and the other half were Spanish elderly people
(68 women and 65 men). Single-group analyses showed an acceptable one-factor
model for both adolescent and elderly groups. Sequential multigroup analyses to
test the equivalence of factor structures for adolescent and elderly groups
showed that factor loadings and variances are not invariant. The scale is
sensitive to age in these groups.
PMID- 11011873
TI - The self-choice elaboration effects on incidental memory of Japanese historical
facts.
AB - The subjects performed an orienting task involving 3 conditions, followed by
unexpected tests which included free recall, name-matching and name-selec tion.
Conditions were designed to force self-generated elaboration, self-choice
elaboration, and experimenter-provided elaboration. In the self-generated
elaboration condition, subjects were presented target sentences, e.g., Nobunaga
ODA burned down ENRYAKUJI Temple, and asked to answer an elaborative
interrogation, e.g., Why did Nobunaga ODA burn down ENRYAKUJI Temple? about each
sentence. In the self-choice elaboration condition, subjects selected one of the
alternative answers to an elaborative interrogation about each sentence. In the
experimenter provided elaboration condition, subjects were presented an answer
which they rated for congruity as the correct answer to the elaborative
interrogation. In the free recall test, self generated elaboration led to better
performance than the other two conditions for which no difference was observed.
However, in the name-matching and name-selection tests, scores were better for
self choice elaboration and self-generated elaboration than for experimenter
provided elaboration. These results were interpreted as demonstrating that self
choice elaboration, in addition to self-generated elaboration, led to effective
encoding in memory.
PMID- 11011874
TI - Sex differences in sport spectator involvement.
AB - Among 107 male and 166 female college students, the present study examined sex
differences in involvement with sports as spectators. A 14-item Likert-type scale
was used to measure the subjects' emotional, cognitive, and behavioral
involvement in sports as spectators. Confirming prior findings, male subjects
exhibited higher involvement with sport spectating than did females. The current
data also provide support for the unidimensionality, reliability, and validity of
the Sport Spectator Involvement Scale.
PMID- 11011875
TI - Relationship between preference for red and locus of control.
AB - The validity of the assumptions about the color red in the Luscher color theory
were examined by correlating preference for red to locus of control and sex.
Undergraduates (100 men and 100 women) who scored < or = 8 or > or = 16 on the
Rotter Internal-External Locus of Control Scale were administered the short form
of the Luscher Color Test. Consistent with the assumptions by Luscher about the
color red, the analysis of variance showed that Internal scorers preferred red
significantly more than External scorers, but no sex difference was found.
PMID- 11011876
TI - Competitive worries, sport confidence, and performance ratings for young
swimmers.
AB - The purpose of this study was to examine the relationships among competitive
worries, sport confidence, and performance of young athletes. Participants were
143 young swimmers aged 11 to 12 years. The athletes completed trait and state
questionnaires (competitive worries and sport confidence) in noncompetitive and
competitive conditions, respectively. The results indicated: (a) significant
relationships among trait and state characteristics and between trait General
Self-confidence and performance ratings in both races as well as between
performance ratings in Races 1 and 2; (b) significant differences in state
variables among athletes with moderate or high and low scores on the trait
variables; (c) significant differences in performance among athletes with
moderate or high and low scores on the trait General Self-confidence and trait
Positive Thinking in Race 1 and on variables trait General Self-confidence, state
General Self confidence, and state Positive Thinking Race 2; and (d) trait
General Self-confidence and trait Confidence in Unfavorable Situations were the
most important predictors of young swimmers' performances. These results may be
useful in application to competitive sports for young athletes. They may help in
psychodiagnostic procedures and may be used for both the content and the
direction of individual programs for psychological preparation of young athletes.
PMID- 11011877
TI - Latin square analysis of variance using summary statistics.
AB - The method for computing a Latin square analysis of variance using summary
statistics is presented.
PMID- 11011878
TI - Comparison of water- and land-based exercise in the reduction of state anxiety
among older adults.
AB - This study examined the effect of an acute exercise program of different exercise
conditions on state anxiety among older adults. 73 healthy subjects were
recruited and randomly assigned to either water exercise group (n = 36) or land
exercise group (n = 37). State anxiety was assessed before exercise and following
exercise. Subjects in the water exercise performed a 70-min. exercise program
consisting of a 10-min. warm-up, a 20-min. brisk walking, a 20-min. rhythmic
dancing, a 10-min. resistance training, and a 10-min. cool down exercise. The
land exercise program contained a 10-min. warm up and a 30-min. combined
endurance and resistance exercise, followed by a 10-min. cool down exercise.
Analysis showed that both exercise groups scored significantly (p<.001) lower on
anxiety after exercise, but there was no significant interaction for group by
trial for scores on state anxiety. The data indicate that elderly persons who
participate in these types of exercise report lower state anxiety.
PMID- 11011879
TI - Suicide and occupation in Hong Kong.
AB - Suicide rates were highest among Service workers and the lowest in Agriculture
workers and fisherfolk in Hong Kong.
PMID- 11011880
TI - Effect of exercise-based cardiac rehabilitation on mobility and self-esteem of
persons after cardiac surgery.
AB - This study adopted an experimental design with using a nonequivalent, posttest
only control group to study the rehabilitation outcomes of 152 persons who
received cardiac surgery. 37 subjects in a rehabilitation group participated in a
2-mo. exercise-based cardiac rehabilitation programme, and another 115 subjects
who did not attend the programme formed the control group. The subjects' self
esteem was measured on the Adult Source of Self-esteem Inventory by Elvoson and
Fleming, and their mobility skill was measured by a simple mobility test based on
New York Heart Association Classification. Analysis of covariance (with
covariance analysis of the subjects' age, years of education, occupational skill,
and mobility skill) indicated that the experimental group scored higher on
positive self esteem and showed significantly better improvement in mobility
skill. The exercise-based cardiac rehabilitation programme positively affected
physical and psychological outcomes. Also, subjects' self-esteem was
significantly correlated with their mobility skills (r=.21, p<.05) among those
aged under 60 years (n=96) but not among those aged 60 or above (n=53).
PMID- 11011881
TI - Loneliness and adaptation among second-generation Portuguese migrants to France:
roles of perceived responsibility and control.
AB - This study explores the association of perceived responsibility for loneliness
and perceived control over loneliness on social adaptation and psychological
adaptation among 109 second-generation Portuguese migrants to France. Analysis
showed that rated perceived control was more highly associated with scores on
social adaptation and psychological adaptation than perceived responsibility.
PMID- 11011882
TI - Incidence of Savant Syndrome in Finland.
AB - The general incidence of Savant Syndrome was assessed in Finland. First, a survey
was made of all 583 facilities which served people with mental retardation.
Second, letters asking for information regarding people with Savant Syndrome were
published in two key Finnish journals of the field. We received reports of 45
cases of Savant Syndrome. This makes an incidence rate of 1.4 per 1,000 people
with mental retardation. The most common form of exceptional skills was calendar
calculation, followed by feats of memory.
PMID- 11011883
TI - Stutterers' vocal reaction times to unilaterally presented high and low frequency
verbs.
AB - The current study investigated vocal reaction times of 11 stuttering participants
to verbs with high and low frequencies of occurrence when these verbs were
unilaterally visually presented. No significant main effects or interactions
between stimuli and visual-half field were found. Reaction times were 16 msec.
faster after right visual field presentations and the Pearson correlation
coefficient between visual fields .71 (p=.02). These results were interpreted as
suggesting that the left hemisphere was dominant for processing the current
lexical items, findings which parallel those for normal speakers.
PMID- 11011884
TI - Response amendment in fencing: differences between elite and novice subjects.
AB - Reaction time (RT), movement time (MT), total response time (RMT), and accuracy
of 3 elite and 3 novice fencers were studied under a dual response paradigm
requiring a full lunge. Electromyographic activity (EMG) from selected arm and
leg muscles was used to compare response profiles of the two groups. Although the
elite subjects had slower MTs, their faster RTs resulted in significantly shorter
total response times. The EMG analysis showed that in comparison to the novice
subjects, onset of muscle activity was significantly faster for the elite group
in five of the six muscles studied. In addition, the elite subjects showed more
coherent muscle synergies and more consistent patterns of muscle coordination.
Although the requirement to change targets (signalled by the arrival of a second
stimulus) led to slightly more target misses for the elite group, the overall
frequency was low, which indicates that it did not pose difficulty for either
group. The present findings show that measures of response timing and
neuromuscular coordination differentiate skill level in the fencing lunge and
draw attention to practical implications for skill assessment and training.
PMID- 11011885
TI - Tactual Performance Test: internal consistency reliability of the memory and
location scores.
AB - Internal consistency reliabilities were computed for the Tactual Performance Test
Memory and Location scores (N=602). After adjusting for unequal item difficulty,
the reliabilities for Memory and Location were .69 and .79, respectively.
PMID- 11011886
TI - Further evidence of associations of type a personality scores and driving-related
attitudes and behaviors.
AB - The present study examined the effects of Type A personality on specific self
reported driving attitudes and behaviors when operating a motor vehicle. 102
undergraduate students completed the student version of the Jenkins Activity
Survey (Form T) and several questionnaires asking participants about their
driving history, driving attitudes, and driving behaviors. When the full range of
Type A scores were examined, Type A personality was significantly related to more
traffic accidents, greater frequency of breaking traffic laws, higher impatience
when driving, more displays of aggression on the road, and engaging in more risky
driving behaviors (rs<.17). When extreme Type A and Type B scores were compared,
Type A drivers reported being involved in significantly more motor vehicle
accidents and reported displaying more aggression on the road. Further research
should examine actual behavioral data using more diverse samples to validate the
results.
PMID- 11011887
TI - A new conceptual model of asymmetry in motor performance for bidimensional fast
oscillating movements in selected variants of performance.
AB - Spatial characteristics and lateral differences between two upper extremities
were investigated in unilateral graphical tasks involving fast oscillating
movements in the vertical plane based on the model of restricted (less than 10
degrees) horizontal abduction adduction in the shoulder joint. The spatial
locations of reversal points were used to identify two groups of motor
performance: with big angles and gross vertical vectors (stretched accordion
group), and small projectile angles with small vertical vectors (compressed
accordion group). Both groups appeared in right and left arm performance. The
former group had a strong pattern of distribution of big and small projectile
angles which reflects a particular variant of execution with a significant
difference between angles and intermittent big and small angles (BB). Two other
variants of execution relating to specific angular patterns of performance were
identified in the compressed accordion group: one (Bs) showed a big difference
between big and small angles but without intermittance; the other (ss) had only
small differences between magnitudes of angles. The Bs variant of execution was
observed only in left-handed performance, whilst ss was typical of both
extremities. The performances affiliated to the stretched accordion group with
the BB variant of execution mostly operated with reciprocal cooperation between
alterations of X and Y vectors for the right arm. Performance related to the same
group with the Bs variant of execution used concurrent collaboration involving
alteration of these vectors for the left arm. The compressed accordion group
which deployed the ss variant of execution mostly displayed concurrent alteration
of vectors irrespective of the side of performance. It is suggested that the
spatial movement strategies might reflect several different schemes of motor
control wherein coupling of oscillators controls vertical and horizontal
movements. It is also proposed that specific subunits of the functional system of
nervous elements responsible for the expression of spatial derivatives of motor
programmes may exist at lower levels of the CNS and might be initiated by the
left brain or by the cooperative activity of the left and right hemispheres.
PMID- 11011888
TI - Arousal and mood factors in the "Mozart effect".
AB - Some investigators of the "Mozart effect" have not controlled for the influence
of differences in arousal or mood induced by treatment conditions. Studies by
Rideout and colleagues reported differences in spatial reasoning after listening
to a Mozart sonata compared against a relaxation instruction tape. The conditions
may have affected subjects' arousal differentially, with the sonata increasing
arousal and the relaxation instructions decreasing arousal, which could have
affected spatial reasoning performance. Evidence is cited in support of this
suggestion and indicates the importance of analyzing the influence of arousal
differences in Mozart effect research.
PMID- 11011889
TI - Re-evaluating Rudolf Laban's choreutics.
AB - The choreutic conception of kinesthetic-motor space originally proposed by Rudolf
Laban is given psychological validation through comparisons with similar
conceptual models in spatial cognition and motor control research. Highly
differentiated systems of reference are distinguished. Spatial paths are mentally
represented as a series of locations linked into polygonal trajectories. Map-like
images of the kinesphere' are structured with polyhedral networks. A fundamental
practice consists of transforming spatial information with various operations
(rotation, reflection, sizing, etc.). Loci are linked into spatial 'scales' which
provide symmetrical solutions to geometric puzzles such as the traveling salesman
problem and those devised by Hamilton (Icosian game) and Euler (Koenigsberg
bridge problem). In the body these are considered to be prototypes for spatial
paths used during adjustments of dynamic equilibrium. The choreutic conception of
polyhedral body space is especially similar to the trajectory formation model.
The choreutic principal of topological forms deflecting across various
kinespheric nets is analogous to N. Bernstein's description of the "net of the
motor field ... as oscillating like a cobweb in the wind." These commonalities
indicate that further critical reviews of "choreutic laws" might be valuable in
suggesting conceptual models and analytical tools for movement study in cognitive
science.
PMID- 11011890
TI - Indoor travel and simple tasks as physical exercise for people with profound
multiple disabilities.
AB - 2 to 4 30-min. periods of indoor travel and simple tasks were arranged daily as
physical exercise for two women with profound mental retardation, deafness, and
profound visual impairment. The questions were whether (a) the women could manage
this fairly extensive exercise regimen (over about 9 and 4.5 mo.) with support
technology and only minimal staff supervision and (b) the exercise could affect
aspects of the women's physical condition. Data indicated that both women could
successfully manage the exercise regimen with support technology, and the
exercise seemed to have some beneficial effects on physical aspects such as bone
metabolism and step width.
PMID- 11011891
TI - Bisection of shapes and lines: analysis of the visual and motor aspects of
pseudoneglect.
AB - This study examined the visual and motor components of pseudoneglect as expressed
on horizontal bisection tasks. Ten participants were tested on bisection of lines
and elliptical shapes and judgement of pretransected lines. Results showed the
same magnitude of leftward error on all three tasks, in contrast to previous
findings for patients with visuospatial neglect who are known to bisect ellipses
and circles much more accurately than lines. Participants' mean line bisection
error was significantly further to the left than the mean subjective midpoint
found on the judgement task. The findings contradict the claim that the visual
component of pseudoneglect is caused by the same mechanism that causes
visuospatial neglect but support the hypothesis that the motor component of
pseudoneglect is similar to directional hypometria.
PMID- 11011892
TI - Recognition of emotional facial expressions in depressed children and
adolescents.
AB - Of the neurobiological models of children's and adolescents' depression, the
neuropsychological one is considered here. Experimental and clinical evidence has
allowed us to identify a lateralization of emotional functions from the very
beginning of development, and a right hemisphere dominance for emotions is by now
well-known. Many studies have also correlated depression with a right hemisphere
dysfunction in patients of different ages. The aim of our study was to analyze
recognition of different facial emotions by a group of depressed children and
adolescents. Patients affected by Major Depressive Disorder recognized less fear
in six fundamental emotions than a group of healthy controls, and Dysthymic
subjects recognized less anger. The group of patients' failure to recognize
negative-aroused facial expressions could indicate a subtle right hemisphere
dysfunction in depressed children and adolescents.
PMID- 11011893
TI - Decision making in dual-task environments: analysis of hemispheric competition
effects.
AB - Performance degradations in multitasking situations have been reported frequently
as a predictable effect of competition that arises from different processing
demands whose hemispheric locations are too proximal. This model might be useful
in explaining performance deficits in complex workplaces. To test this assertion,
a laboratory study was designed to create an analogue of the processing demands
required by a tactical decision-making task performed by 24 right-handed men.
Vocalization, dichotic listening and decision-making performance were assessed
under single- and dual-task conditions. The results were consistent with the
predictions from hemispheric competition in the case of dichotic listening but
not with vocalization. The results are discussed in terms of their implications
for both research and systems design.
PMID- 11011894
TI - Relationships between physical education classes and the enhancement of fifth
grade pupils' self-concept.
AB - Physical education classes given to a group of 46 pupils (27 boys and 19 girls)
over a 6-mo. term differed from the usual program (control group of 29 pupils) in
identifying individual goals, promoting participative and noncompetitive games,
and praising students every chance possible during the classes. The enhancement
of self-concept, particularly the physical self-concept, was significant for the
experimental group as measured by the Self-description Questionnaire and the
Child and Youth Physical Self-perception Profile.
PMID- 11011895
TI - Differences in reactions to paintings by male and female college students.
AB - 38 male and 55 female college students rated digitized color facsimiles of 40
paintings that varied in artistic period (Renaissance, Rococo, Impressionist,
Post-Impressionist, 20th Century) and subject matter (portrait, landscape, still
life, behavior depiction) on 12 7-point semantic differential scales, e.g.,
simple-complex. Women judged the content of Rococo and Impressionist paintings as
more pleasing than did men and Impressionist paintings evoked greater feelings of
pleasure and relaxation among women than among men. In addition, paintings that
depicted behaviors evoked more pleasure and alertness among women than among men.
The results were interpreted in terms of underlying differences between men and
women in perceptual style and emotional sensitivity.
PMID- 11011896
TI - Thoughts regarding the qualitative analysis of human movement.
AB - The qualitative analysis of human movement is composed of many parts. Trying to
assess the contribution of each of these components to the whole process of
qualitative analysis is difficult. Evaluating a qualitative approach to human
movement analysis using quantitative procedures can lead to misinterpretations.
Qualitative analysis of movement has components important to its success which
cannot be gauged by traditional biomechanical standards.
PMID- 11011897
TI - Optimization characteristics of walking with and without a load on the trunk of
the body.
AB - Previous work showed that subjects naturally adopt a walking speed which
optimizes energy cost of locomotion and stability of stride; however, no studies
have examined whether these criteria are affected by carrying an external load.
The purpose of this study was to compare optimization characteristics during
loaded or unloaded walking. Energy cost and stride characteristics were measured
for 10 subjects with and without a load on the trunk of the body of 10% of the
body weight during 4 sessions. The first 2 sessions represent free walking at
2.5, 3, 3.5, 4, 4.5, and 5 km x hr.(-1). The last sessions represent free vs
forced walking at constant speed (preferred frequency and +/- 10 PF and +/-20% of
preferred frequency). Results show an effect of load on energy cost of walking
but no effect on the optimal speed for stability. Furthermore, when carrying a
load the subject does not adopt systematically the speed that minimizes
physiological cost. Our findings suggest the necessity to consider this effect to
prevent gait disturbance and maintain the health benefits of walking.
PMID- 11011898
TI - Right to left hemispheric shift in occipital electroencephalographic responses to
repeated Kimura figures.
AB - Gordon and Carmon (1976) reported that repeated presentations of an initially
novel stimulus were associated with a transfer of cerebral dominance over time
(trials) from the right to the left hemisphere. To test the generalizability of
these results the proportions of alpha rhythms over the left and right occipital
and parietal lobes were measured following the presentation of recurring and
nonrecurring complex visual patterns (the Kimura Figures) to the upper or lower,
left or right peripheral visual fields. Analysis showed increased electrical
activation (as inferred by attenuated proportions of alpha rhythms) of the left
occipital lobe but decreased activation of the right occipital lobe. This shift
occurred during repeated presentations of the same stimuli but not during single
presentations of different novel stimuli. There was no significant shift in this
activity over the parietal lobes. These results are consistent with the reports
of other researchers who have found a shift of dominant neuroelectrical activity
from the right to the left hemisphere as the novelty of a visuospatial stimulus
decreases.
PMID- 11011899
TI - Relation of useful field of view and other screening tests to on-road driving
performance.
AB - The purpose of this study was to examine the value of a clinical driving
assessment battery in predicting performance on an on-road driving test. 43
participants referred to the Bryn Mawr Rehab Adapted Driving Program for
evaluation of driving ability underwent an evaluation consisting of a predriver
screening and an on road driving test. The predriver screening included a vision
screening, a reaction rime task, a split-attention task, the Hooper Visual
Organization Test, verbal and symbolic sign recognition, and assessment of Useful
Field of View. Logistic regression analyses were applied to identify which
predriver screening variables could be used to predict outcome on the on road
driving test (pass/fail); UFOV was that best single predictor. The addition of
screening tests beyond UFOV alone did not increase predictive validity. These
findings suggest that UFOV may serve as an indicator of the need for further
driving assessment.
PMID- 11011900
TI - Chronic stress affects blood pressure and speed of short-term memory.
AB - Subjects high and low on chronic stress (daily hassles) were engaged in a short
term memory-scanning task with (n = 12) or without (n = 12) an active listening
task. Blood pressure and heart rate were obtained before and during the
experiment. Subjects with high stress were slower in short-term memory
processing, had higher systolic blood pressure and heart rate (at baseline and
during task performance), and reported more health complaints than those low in
stress. The processing efficiency theory may predict slower memory scanning in
subjects with high chronic stress, as part of these subjects' working memory
capacity is taken up by more worries than that of the other subjects. Speed of
short-term memory was even lower for subjects with high stress when performing
the memory task in the active listening condition.
PMID- 11011901
TI - Effects of speaker variability and phoneme location on speech perception.
AB - The effects of variation in a speaker's voice and temporal phoneme location were
assessed through a series of speeded classification experiments. Listeners
monitored speech syllables for target consonants or vowels. The results showed
that speaker variability and phoneme-location variability had detrimental effects
on classification latencies for target sounds. In addition, an interaction
between variables showed that the speaker variability effect was obtained only
when temporal phoneme location was fixed across trials. A subadditive decrement
in latencies produced by the interaction of the two variables was also obtained,
suggesting that perceptual loads may not affect perceptual adjustments to a
speaker's voice in the same way that memory loads do.
PMID- 11011902
TI - Assessment of visual-motor coordination in 6- to 11-yr.-olds.
AB - The concurrent and content validity of the Rey-Osterrieth Complex Figure Test and
the Beery Developmental Test of Visual-Motor Integration-Third Revision were
investigated through correlational analysis. 432 children, ages 6 to 11 years,
were administered both tests. Across age groups participants performed better on
both measures, providing support for the similarity of the measures and their
sensitivity to the development of visuomotor integration. Although analysis
indicated considerable overlap in the content of the two scales, the shared
variance ranged from 7% to 31%, depending on the age of the child. The Rey
Osterrieth figure is composed of overlapping squares, rectangles, triangles, and
various other shapes. Given this complex combination, scores on this test reflect
the examinees' visual organization and motor planning skills. On the other hand,
the Beery test consists of a series of shapes which progress from simple figures
to more complex ones. Because the figures become more difficult to copy, the
score on this test reflects the examinees' developmental level of visuomotor
ability. Despite these differences in test stimuli and interpretation of
performance, the present study showed considerable shared variance in the scores
of the examinees who took both tests. Finally, local norms for the Rey-Osterrieth
figure using the scoring approach of E. M. Taylor (1959, adapted from Osterrieth,
1944) and including standard scores are presented for children ages 6 to 11
years.
PMID- 11011903
TI - Effects of minimal exercise and cognitive behavior modification on adherence,
emotion change, self-image, and physical change in obese women.
AB - The present investigation tested a 12-wk. treatment protocol which employed low
intensity cardiovascular and resistance exercise as well as cognitive-behavior
modification on 13 obese, previously sedentary women. Separate analyses were
conducted on program maintenance, emotional change, and physiological change.
Although self motivation was lower in the treatment group than in the control
group (n=35), measures of exercise maintenance were significantly higher.
Analyses within the treatment group only indicated significant improvements in
measures of State Anxiety, Depression, Anger, Fatigue, Tension, and Vigor, also
Health Evaluation, Body Area Satisfaction, and heightened Overweight
Preoccupation, over the 12 weeks. Their feelings after individual bouts of
exercise indicated significantly increased Positive Engagement, Revitalization,
and Tranquility, and reduced Physical Exhaustion. Maximum volume of oxygen uptake
(VO2max) significantly increased (2nd to 10th percentile), but not resting heart
rate. No significant correlation was found between cardiorespiratory change and
change in scores on depression and anxiety. No significant association was found
between physiological change and change in body image. Preliminary evaluation of
the minimal exercise treatment was given. The need to replicate findings with
larger and different samples was emphasized.
PMID- 11011904
TI - Environmental events and induction of metamotivational reversals.
AB - Three administrations of the Telic State Measure were used to test the notion
from reversal theory that environmental events may induce reversals in
metamotivational state. Significant changes in scores on Telic State Measure
items from three different groups of students experiencing three different
environmental events and one student control group (total N=96) confirmed that
unexpected environmental events could induce reversals from the telic to the
paratelic metamotivational state.
PMID- 11011905
TI - Development of a random response scale for the multiple affect adjective check
list-revised.
AB - A scale was constructed to identify random responses on the Multiple Affect
Adjective Check List-Revised. Items chosen were the 14 least frequently checked
items and 14 most frequently checked items, plus the seven most frequently
checked negative items and the seven least frequently checked positive items
(total=42). The Random Response Scale successfully differentiated random
protocols from those produced by 420 college students, and scores on the scale
were significantly higher for the college students than for the random sample. In
addition, correlations between scores on the Random Response Scale and the
Communality Scale (Adjective Check List) and the NEO-FFI Conscientiousness Scale
suggest its usefulness as a measure of "conscientiousness" or "dependableness."
PMID- 11011906
TI - Illusory correlation: a function of availability or representativeness
heuristics?
AB - The present study sought to investigate the illusory correlation phenomenon by
experimentally manipulating the availability of information through the use of
the "lag" effect (Madigan, 1969). Seventy-four university students voluntarily
participated in this study. Similar to Starr and Katkin's (1969) methodology,
subjects were visually presented with each possible combination of four
experimental problem descriptions and four sentence completions that were paired
and shown twice at each of four lags (i.e., with 0, 2, 8 and 20 intervening
variables). Subjects were required to make judgements concerning the frequency
with which sentence completions and problem descriptions co-occurred. In
agreement with previous research (Starr & Katkin, 1969), the illusory correlation
effect was found for specific descriptions and sentence completions. Results also
yielded a significant effect of lag for mean ratings between 0 and 2 lags;
however, there was no reliable increase in judged co-occurrence at lags 8 and 20.
Evidence failed to support the hypothesis that greater availability, through the
experimental manipulation of lag, would result in increased frequency of co
occurrence judgements. Findings indicate that, in the present study, the illusory
correlation effect is probably due to a situational bias based on the
representativeness heuristic.
PMID- 11011907
TI - Effects of obesity and body fat distribution on lipids and lipoproteins in
nondiabetic American Indians: The Strong Heart Study.
AB - OBJECTIVES: To examine the relationship between obesity and lipoprotein profiles
and compare the effects of total obesity and central adiposity on
lipids/lipoproteins in American Indians. RESEARCH METHODS AND PROCEDURES:
Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74
years participating in the Strong Heart Study. Total obesity was estimated using
body mass index (BMI). Central obesity was measured as waist circumference.
Lipoprotein measures included triglycerides, high-density lipoprotein (HDL)
cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein AI
(apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses
were used to examine the associations between obesity and lipids/ lipoproteins.
RESULTS: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2
kg/m2) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m2), but there was no
sex difference in waist circumference. Men had higher apoB and lower apoAI levels
than did women. In women, when adjusted for center, gender, and age, BMI was
significantly related to HDL cholesterol (r = -0.24, p < 0.001). There was a
significant but weak relation with apoAI (r = -0.14, p < 0.001). Waist
circumference was positively related to triglycerides (r = 0.14, p < 0.001) and
negatively related to HDL cholesterol (r = -0.23, p < 0.001) and apoAI (r =
0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r =
0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = -0.35, p <
0.001) and apoAI (r = -0.23, p < 0.001). Triglycerides increased with waist
circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist
circumference (r = -0.36, p < 0.001). In both women and men there was an inverted
U-shaped relationship between obesity and waist with LDL cholesterol and apoB. In
canonical correlation analysis, waist circumference received a greater weight
(0.86) than did BMI (0.17) in women. However, the canonical weights were similar
for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (-1.02) carried
greater weight in women, whereas in men, triglycerides (0.50), and HDL
cholesterol (-0.64) carried a large amount of weight. All the correlation
coefficients between BMI, waist circumference, and the first canonical variable
of lipids/lipoproteins or between the individual lipid/lipoprotein variables and
the first canonical variable of obesity were smaller in women than in men.
Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI
and waist circumference in men. All lipid/lipoprotein changes in women in
relation to BMI and waist circumference were minimal. DISCUSSION: The main
lipoprotein abnormality related to obesity in American Indians was decreased HDL
cholesterol, especially in men. Central adiposity was more associated with
abnormal lipid/lipoprotein profiles than general obesity in women; both were
equally important in men.
PMID- 11011908
TI - Lifetime overweight status in relation to serial changes in body composition and
risk factors for cardiovascular disease: The Fels Longitudinal Study.
AB - OBJECTIVE: The aims were to determine if 1) individuals who became and maintained
overweight during their entire lifetime differ from those who were never
overweight in terms of annual changes in adiposity and concurrent changes in
cardiovascular disease (CVD) risk factors; 2) the changes and their relationships
to each other varied between these groups or by sex within the groups; and 3)
alcohol usage, smoking habits, and level of physical activity differed between
groups. RESEARCH METHODS AND PROCEDURES: Data from 16,315 examinations of 414
individuals were utilized to assess lifetime overweight (body mass index [BMI] >
25 kg/m2) status. A regressive analytic approach was used to determine the
average annual changes for each individual over an adult serial interval ranging
from 4 to 20 years. RESULTS: Men and women who have become and maintained
overweight have higher blood pressure and a poorer lipid/lipoprotein risk profile
than those who have never been overweight. There is an accelerated deterioration
in the atherogenic profile of overweight men and women as indicated by annual
changes in CVD risk factors about double that of their never-overweight
counterparts. In women, increased risk is derived from increasing systolic and
diastolic blood pressure, whereas in men the increased risk comes not only from
increasing diastolic blood pressure but also cholesterol, triglycerides, and low
density lipoprotein cholesterol levels and, to a lesser extent, decreasing high
density lipoprotein cholesterol. DISCUSSION: The reduced physical activity
observed in the overweight adults may be related to their accumulation of adipose
tissue at a rate about double their never-overweight counterparts, and this may
be driving the higher rate of increase of CVD risk factors in the overweight
groups.
PMID- 11011909
TI - Effects of sibutramine plus orlistat in obese women following 1 year of treatment
by sibutramine alone: a placebo-controlled trial.
AB - OBJECTIVE: This study assessed whether adding orlistat to sibutramine would
induce further weight loss in patients who previously had lost weight while
taking sibutramine alone. RESEARCH METHODS AND PROCEDURES: Patients were 34 women
with a mean age of 44.1 +/- 10.4 years, weight of 89.4 +/- 13.8 kg, and body mass
index (BMI) of 33.9 +/- 4.9 kg/m2 who had lost an average of 11.6 +/- 9.2% of
initial weight during the prior 1 year of treatment by sibutramine combined with
lifestyle modification. Patients were randomly assigned, in double-blind fashion,
to sibutramine plus orlistat or sibutramine plus placebo. In addition to
medication, participants were provided five brief lifestyle modification visits
during the 16-week continuation trial. RESULTS: Mean body weight did not change
significantly in either treatment condition during the 16 weeks. The addition of
orlistat to sibutramine did not induce further weight loss as compared with
treatment by sibutramine alone (mean changes = +0.1 +/- 4.1 kg vs. +0.5 +/- 2.1
kg, respectively). DISCUSSION: These results must be interpreted with caution
because of the study's small sample size. The findings, however, suggest that the
combination of sibutramine and orlistat is unlikely to have additive effects that
will yield mean losses > or =15% of initial weight, as desired by many obese
individuals.
PMID- 11011910
TI - Does weight loss maintenance become easier over time?
AB - OBJECTIVE: Studies of health-related behaviors, including weight loss, have shown
that risk of relapse decreases over time, although reasons for this relationship
are unclear. The purpose of this cross-sectional study was to determine if
subjects who have maintained weight losses for varying periods of time report
different strategies for weight loss maintenance or differences in the effort and
pleasure associated with weight maintenance behaviors. RESEARCH METHODS AND
PROCEDURES: Subjects were 758 women and 173 men who had maintained losses of at
least 30 lb (mean = 60 lb) for 2 years or longer (mean = 6.8 +/- 7.0 years). Self
administered questionnaires assessed subjects' use of weight maintenance
strategies in the past year and their perceptions of the effort, attention, and
pleasure associated with weight maintenance. RESULTS: Subjects who had maintained
weight losses longer used fewer weight maintenance strategies and reported that
less effort was required to diet and maintain weight and that less attention was
required to maintain weight. The pleasure derived from exercise, low-fat eating,
and maintaining weight was unrelated to duration of weight loss maintenance.
DISCUSSION: As duration increases, a shift in the balance between the effort and
pleasure of weight maintenance may occur. This shift may increase the likelihood
of continued maintenance.
PMID- 11011911
TI - Occupational status, cortisol secretory pattern, and visceral obesity in middle
aged men.
AB - OBJECTIVE: Despite several studies indicating that social gradients are
predictive of cardiovascular mortality, the pathogenetic mechanisms remain
incompletely understood. RESEARCH METHODS AND PROCEDURES: A population sample of
51-year-old men (N = 284) was divided into a socioeconomic gradient with manual
laborers, civil servants, and university graduates. Anthropometric measurements
were registered. Cortisol concentrations were measured in saliva, collected
repeatedly during an ordinary working day, and a low-dose dexamethasone
suppression test was performed. RESULTS: Lower socioeconomic status was
associated with visceral obesity and higher cortisol values in relation to
perceived stress. However, total cortisol secretion over the day of study was not
elevated. The regulation of cortisol secretion showed less plasticity and
dexamethasone inhibition was less efficient in the men in the lower socioeconomic
status group than in those with a higher socioeconomic status. These are known
consequences of long term stress. Longer duration in low socioeconomic conditions
seemed to worsen these phenomena. DISCUSSION: It was concluded that a low
socioeconomic status is associated with perturbed cortisol secretion, which is
elevated in relation to perceived stress. When the hypothalamic-pituitary-adrenal
axis is subjected to prolonged increases in cortisol elicited by chronic stress,
the regulation of cortisol secretion is affected, indicating neuroendocrine
dysregulations. These observations may provide a means for understanding the
association of socioeconomic impairments with visceral obesity and the social
inequality in risk for prevalent and serious diseases.
PMID- 11011912
TI - Teasing history, onset of obesity, current eating disorder psychopathology, body
dissatisfaction, and psychological functioning in binge eating disorder.
AB - OBJECTIVE: The primary goal of this study was to examine associations among
teasing history, onset of obesity, current eating disorder psychopathology, body
dissatisfaction, and psychological functioning in women with Binge Eating
Disorder (BED). RESEARCH METHODS AND PROCEDURES: Subjects were 115 female adults
who met DSM-IV criteria for BED. Measurements assessing teasing history (general
appearance [GAT] and weight and size [WST] teasing), current eating disorder
psychopathology (binge frequency, eating restraint, and concerns regarding
eating, shape, and weight), body dissatisfaction, and psychological functioning
(depression and self-esteem) were obtained. RESULTS: History of GAT, but not WST,
was associated with current weight concerns and body dissatisfaction, whereas
both GAT and WST were significantly associated with current psychological
functioning. Patients with earlier onset of obesity reported more WST than
patients with later onset of obesity, but the groups did not differ significantly
in GAT, current eating disorder psychopathology, body dissatisfaction. or
psychological functioning. Obese women reported more WST than non-obese women,
but no differences in GAT or the other outcome variables were observed. Higher
frequency of GAT was associated with greater binge frequency in obese women, and
with greater eating restraint in non-obese women. DISCUSSION: Although physical
appearance teasing history is not associated with variability in most eating
disorder psychopathology, it is associated with related functioning, most notably
body dissatisfaction, depression, and self-esteem. Our findings also suggest that
the age of onset of obesity and current body mass index status in isolation are
not associated with eating psychopathology or associated psychological
functioning in adult patients with BED.
PMID- 11011913
TI - Obesity management: Australian general practitioners' attitudes and practices.
AB - OBJECTIVES: To document general practitioners' (GPs) attitudes and practices
regarding the prevention and management of overweight and obesity. RESEARCH
METHODS AND PROCEDURES: A cross-sectional survey of a randomly selected sample of
1500 Australian GPs was conducted, of which 752 questionnaires were returned. The
measures included views on weight management, definitions of success, views
regarding the usefulness of drugs, approaches to and strategies recommended for
weight management, and problems and frustrations in managing overweight and
obesity. RESULTS: GPs view weight management as important and feel they have an
important role to play. Although they consider themselves to be well prepared to
treat overweight patients, they believe that they have limited efficacy in weight
management and find it professionally unrewarding. GPs view the assessment of a
patient's dietary and physical activity habits and the provision of dietary and
physical activity advice as very important. The approaches least likely to be
considered important and/or least likely to be practiced were those that would
support the patient in achieving and maintaining lifestyle change. DISCUSSION:
There remains considerable opportunity to improve the practice of GPs in their
management of overweight and obesity. Although education is fundamental, it is
important to acknowledge the constraints of the GPs' existing working
environment.
PMID- 11011914
TI - Differential expression of leptin receptor in high- and low-fat-fed Osborne
Mendel and S5B/Pl rats.
AB - OBJECTIVE: The regulation of body weight and body composition involves input from
genes and the environment. This interaction is demonstrated by the different
susceptibility of Osborne-Mendel (OM) and S5B/P1 rat strains to obesity when
offered a high-fat diet. In animals and humans, diet-induced obesity has been
characterized by hyperleptinemia, which has been interpreted as evidence for
leptin resistance. This investigation determined if altered expression of leptin
receptors (ObR) in the hypothalamus could potentially contribute to altered
sensitivity to diet-induced obesity between OM and S5B/P1 rats. RESEARCH METHODS
AND PROCEDURES: OM and S5B/P1 rats were fed high-fat (HF) or low-fat (LF) diets
for 14 days. Ribonuclease protection assays and Western blotting were used to
assay the levels of mRNA and protein, respectively, for short (ObR-S) and long
(ObR-L) forms of the leptin receptor in the hypothalamus. RESULTS: The mRNA
encoding ObR-L, the predominant signaling form of the receptor, was higher in OM
rats than in S5B/P1 rats (p < 0.01) both on HF and LF diets. No changes in ObR-L
mRNA expression were observed in OM rats with diet, but, S5B/P1 rats showed a
slight increase in the ObR-L on the LF diet. On the contrary, there were no
changes in ObR-S mRNA expression due to diet or strain. Western blots showed that
both the short and long forms of the receptor were increased on the LF diet, but
there were no strain differences. OM and SSB/P1 rats had comparable leptin levels
after maintenance on a LF diet (6.20 +/- 0.63 and 4.81 +/- 0.82 ng/mL,
respectively). Serum leptin levels in OM rats were increased by the HF diet and
were elevated 2-fold over those of their S5B/P1 counterparts. DISCUSSION: These
results suggest that a decrease in the levels of both the long form and short
form of the receptor may contribute to the leptin resistance seen in HF-fed rats.
These effects appear to be post-transcriptional, because equivalent changes were
not observed in the expression of ObR-L and ObR-S mRNAs. They may be related to
the increase in circulating leptin levels, suggesting that high serum leptin
levels contribute to increased leptin resistance and subsequently lead to
obesity. We conclude that down-regulation of receptor protein levels is
associated with hypothalamic leptin resistance of HF-fed rats.
PMID- 11011915
TI - Augmented insulinotropic action of arachidonic acid through the lipoxygenase
pathway in the obese Zucker rat.
AB - OBJECTIVE: The metabolism of arachidonic acid (AA) has been shown to be altered
in severe insulin resistance that is present in obese (fa/fa) Zucker rats. We
examined the effects and mechanism of action of AA on basal and glucose
stimulated insulin secretion in pancreatic islets isolated from obese (fa/fa)
Zucker rats and their homozygous lean (Fa/Fa) littermates. RESEARCH METHODS AND
PROCEDURES: Islets were isolated from 10- to 12-week-old rats and incubated for
45 minutes in glucose concentrations ranging from 3.3 to 16.7 mM with or without
inhibitors of the cyclooxygenase or lipoxygenase pathways. Medium insulin
concentrations were measured by radioimmunoassay, and islet production of the 12
lipoxygenase metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), was measured
by enzyme immunoassay. RESULTS: In islets from lean animals, AA stimulated
insulin secretion at submaximally stimulatory glucose levels (<11.1 mM) but not
at 16.7 mM glucose. In contrast, in islets derived from obese rats, AA
potentiated insulin secretion at all glucose concentrations. AA-induced insulin
secretion was augmented in islets from obese compared with lean rats at high
concentrations of AA in the presence of 3.3 mM glucose. Furthermore, the
inhibitor of 12-lipoxygenase, esculetin (0.5 microM), inhibited AA-stimulated
insulin secretion in islets from obese but not lean rats. Finally, the islet
production of the 12-HETE was markedly enhanced in islets from obese rats, both
in response to 16.7 mM glucose and to AA. DISCUSSION: The insulin secretory
response to AA is augmented in islets from obese Zucker rats by a mechanism
related to enhanced activity of the 12-lipoxygenase pathway. Therefore, augmented
action of AA may be a mechanism underlying the adaptation of insulin secretion to
the increased demand caused by insulin resistance in these animals.
PMID- 11011916
TI - Allergic contact dermatitis from hydrangea--is it so rare?
AB - 8 cases of allergic contact dermatitis from hydrangea seen in Angers, France,
during the last 15 years are reported and compared to other cases found in the
literature. In this review, allergic contact dermatitis from hydrangeas appears
to be an occupational dermatosis among nursery workers, presenting as an eczema
involving the hands and especially the first 3 fingers, with chronic features of
fissuring and scaling and with a chronic course. Differential diagnosis from
irritant contact dermatitis may be difficult. Patch tests with the stem as well
as the leaf of hydrangeas gave strong positive reactions in all patients, and
hydrangenol, the allergen of hydrangea, when tested, always also gave a positive
reaction. Sensitization seems to occur after close and prolonged contact with the
plant, which could explain the relative frequency in Angers because it provides
almost 90% of hydrangea seedling production in France.
PMID- 11011917
TI - Contact allergy and hand eczema in Swedish dentists.
AB - Hand eczema and contact allergy in Swedish dentists were studied in a
multidisciplinary project. The aims of the study were to establish diagnoses, to
investigate the occurrence of contact allergy, in particular to (meth)acrylates,
and to evaluate certain consequences of hand eczema. A postal questionnaire on
skin symptoms, atopy and occupational experience was mailed to 3,500 dentists
aged <65 years, and licensed 1965-1995. The response rate was 88%. Among dentists
living in 3 major cities, 14.9% (n= 191) reported hand eczema during the previous
year. They were invited to a clinical examination, including patch testing with a
standard and a dental series. 158/191 (83%) dentists attended, and hand eczema
diagnosis was confirmed in 149/158 (94%). Irritant contact dermatitis was
diagnosed in 67% and allergic contact dermatitis in 28%. On patch testing, 50%
presented at least 1 positive reaction. The most frequent allergens were nickel
sulfate, fragrance mix, gold sodium thiosulfate and thiuram mix. 7 (5%) had
positive reactions to (meth)acrylates, all to 2-hydroxyethyl methacrylate and 6
also to ethyleneglycol dimethacrylate. 38% had consulted a physician, 4% had been
on sick-leave and 1% had changed occupational tasks due to hand eczema. No
dentist with allergy to acrylates had been on sick-leave or changed occupation.
It is concluded that dentistry is a high-risk occupation for hand eczema, and
that irritant contact dermatitis is most common. The prevalence of contact
allergy to acrylates was below 1% in the population of responding dentists, and
in most cases did not have serious medical, social or occupational consequences.
PMID- 11011918
TI - Dyshidrotic eczema and occupation: a descriptive study.
AB - Dyshidrotic eczema (DE) is a chronic and/or recurrent vesicular eczema of the
palmar sides of the hands and sometimes the soles of the feet. The major
aetiologies to be considered are atopic DE, contact DE, systemic contact DE and
DE due to fungal or microbial allergy. To clarify the role of occupational
contact allergens, 59 workers with DE were examined to determine whether they had
atopy, environmental contact sensitization and/or contact allergy coupled with
work activity. For all, patch testing was carried out using the European standard
series and the material brought in by the patients. No significant difference was
found between the rate (42.4%) of history of atopy among the 59 workers with DE
and that (30.6%) observed among 160 workers with other forms of hand eczema (HE).
Positive patch test reactions were found in 72.8% of dyshidrotic patients. A
relationship to occupational activity was strong for 18 (30.5%) of them but this
rate was significantly lower than that (55%) observed among the 160 with other
types of eczema. Results of the present study showed that contact sensitization
is as much involved in workers with DE as in workers with other form of HE, even
though the relationship to work is significantly less frequent for DE. It also
suggests that atopic histories are no more involved in DE than in other forms of
HE.
PMID- 11011919
TI - Lymphocyte subset changes in blood and gastrointestinal mucosa after oral nickel
challenge in nickel-sensitized women.
AB - This study investigates lymphocyte subsets in both the gastrointestinal mucosa
and blood, in patients with nickel allergic contact dermatitis, after 10 mg oral
nickel challenge (double-blind, placebo-controlled). 6 such patients with
cutaneous symptoms induced only by skin contact with nickel (group A), 6 with a
flare-up of cutaneous symptoms after food nickel ingestion (group B) and 6
healthy controls (group C) were enrolled. Blood lymphocyte subsets (CD4, CD45RO,
CD8) were analyzed before and after 4 and 24 h from the challenge (test 1, 2, and
3), and intestinal biopsies were performed 2 days later. Challenges were positive
in group B and negative in group A and controls. Serum and urine nickel levels
significantly increased after nickel ingestion, with no differences between the 3
groups. At test 3, a significant decrease of the all CDs studied was found in
group B. Biopsies of this group showed higher levels of CD45RO+ cells in the
lamina propria and in the epithelium and lower levels of epithelial CD8+
lymphocytes. This study confirms that ingested nickel may induce flare-up of
cutaneous reactions in some nickel-allergic patients, independently of the degree
of sensitization and the intake of metal. In these patients, oral nickel
stimulates the immune system, inducing maturation of T lymphocytes from virgin
into memory cells; these latter cells seem to accumulate in the intestinal
mucosa. The immunoreaction also involves CD8+ cells, whose role is not yet clear.
PMID- 11011920
TI - Repeated exposures to cobalt or chromate on the hands of patients with hand
eczema and contact allergy to that metal.
AB - The present study aimed at evaluating the effects of daily repeated exposures to
low cobalt or chromate concentrations on the hands of patients with hand eczema
and cobalt or chromate allergy. For 2 weeks, the patients immersed a finger for
10 min daily into the appropriate metal salt solution in water. During the 1st
week, this was a 10 or 50 mg/l cobalt concentration or a 10 mg/l chromate
concentration, and, during the 2nd week, a 100 or 200 mg/l cobalt concentration
or a 100 mg/l chromate concentration. This regimen elicited a flare of hand
eczema only in the chromate-exposed chromate-sensitive patients. During the
exposure period, accumulation of cobalt or chromate in the nail was demonstrated.
Standardization of chemical methods of quantification of skin exposure to
allergens, combined with experimental exposure studies in patients with specific
contact allergy, will increase the possibility of providing evidence-based
medicine in the area of allergic contact dermatitis in the future.
PMID- 11011922
TI - Contact urticaria from panthenol in hair conditioner.
PMID- 11011921
TI - Multicentre study of allergic contact cheilitis from toothpastes.
AB - The present work reports the results of a multicentre study of toothpaste
allergic contact cheilitis (TACC) conducted by GIRDCA (Gruppo Italiano Ricerca
Dermatiti da Contatto e Ambientali). The study examined 54 patients with
eczematous lesions on the lips, the possible cause of which was suspected to be
the use of toothpastes. Patch tests were conducted with a standard series, a
specially-targeted series (toothpaste cheilitis series, TCS), and with suspected
toothpaste(s). A stop-restart test (SRT) was carried out with these, together
with a use test to identify possible alternative products. The TCS produced 17
positive reactions in 13 patients, the most frequent being to spearmint oil. Of
the 54 patients, 5 displayed positive reactions only to the TCS. The patch tests
with toothpaste produced positive reactions in 11/32 patients, the SRT a positive
response in 10/12 cases. The diagnosis of TACC was confirmed in 15/54 patients.
Alternative products were identified for 5 patients. In conclusion, the allergens
most frequently responsible for TACC were the flavourings, and the additional
series proved to be useful in many cases (together with patch tests with
toothpastes and the SRT) for correct diagnosis and to initiate effective
prevention.
PMID- 11011923
TI - Allergic contact dermatitis due to diphenylthiourea in a neoprene slimming suit.
PMID- 11011924
TI - Occupational contact dermatitis from diethylene glycol monobutyl ether in a
podiatrist.
PMID- 11011925
TI - A case of contact hypersensitivity to platinum salts.
PMID- 11011926
TI - A series of 3 patients sensitized to reactive dyes during patch testing.
PMID- 11011927
TI - The role of nickel in oral disease.
PMID- 11011928
TI - Photoallergic eczema caused by sunscreens in a 12-year-old girl.
PMID- 11011929
TI - Occupational contact urticaria syndrome from cefotiam dihydrochloride in a latex
allergic nurse.
PMID- 11011930
TI - Contact allergy to doxepin.
PMID- 11011931
TI - Chronic urticaria from an acrylic dental prosthesis.
PMID- 11011933
TI - Allergic contact dermatitis due to 1,3-butylene glycol.
PMID- 11011932
TI - Allergic contact dermatitis from diethyl sebacate in lanoconazole cream.
PMID- 11011934
TI - An outbreak of occupational textile dye dermatitis from Disperse Blue 106.
PMID- 11011935
TI - Di(2-ethylhexyl) phthalate (DOP) in the dotted polyvinyl-chloride grip of cotton
gloves as a cause of contact urticaria syndrome.
PMID- 11011937
TI - Cucumber contact dermatitis.
PMID- 11011936
TI - The biocide iodopropynyl butylcarbamate (IPBC) as an allergen in cutting oils.
PMID- 11011938
TI - Allergic contact dermatitis from formaldehyde and quaternium-15 in photocopier
toner.
PMID- 11011940
TI - Allergic contact dermatitis from chromate and 4-tert-butylphenol-formaldehyde
resin in a father and daughter.
PMID- 11011939
TI - Allergic contact dermatitis from airborne exposure to acrylates.
PMID- 11011941
TI - Hydrolyzed protein shampoo additives are not a common contact allergen.
PMID- 11011942
TI - Contact anaphylaxis due to hair dye.
PMID- 11011943
TI - Immediate, anaphylactic and delayed reactions to jellyfish.
PMID- 11011944
TI - Occupational UVA-induced allergic photodermatitis in a welder due to
hydrochlorothiazide and ramipril.
PMID- 11011945
TI - Systemic contact dermatitis from implanted disulfiram.
PMID- 11011946
TI - Sorbic acid: an unusual cause of systemic contact dermatitis in an infant.
PMID- 11011947
TI - Contact dermatitis from parabens used as preservatives in eyedrops.
PMID- 11011948
TI - Delayed-type hypersensitivity to heparin with tolerance of its intravenous
administration.
PMID- 11011949
TI - Occupational contact dermatitis from ylang-ylang oil.
PMID- 11011950
TI - Overweight and obesity in European children and adolescents.
AB - The conclusions of this mini-workshop are not substantially different from those
previously published based on the USA experience [9]. This does not necessarily
mean that there are no important differences between Europe and the USA, rather
it reflects the paucity of data, especially in Europe. Moreover, European data
are dominated by studies in Northern and Western European countries, which are
closest in economic terms to the USA. This review has not been able to reflect
the position in the less economically advantaged parts of Europe where more
substantial differences may occur. Together, these reviews have highlighted the
limited and inadequate data available on one of the most important and burgeoning
public health problems in the world today. There is an urgent need for more
research into the fundamental mechanisms of weight gain and effective
interventions if we are to prevent the next generation becoming fatter than their
parents.
PMID- 11011951
TI - Overweight and obesity in European children and adolescents: causes and
consequences, treatment and prevention. An introduction.
PMID- 11011952
TI - Overweight and obesity in European children: definition and diagnostic
procedures, risk factors and consequences for later health outcome.
AB - In this article, information on the definition of obesity in childhood and
adolescence, its differential diagnosis and its adverse health effects is
provided. This information can be considered as a basis for the evaluation of an
obese patient. Review of the international and European literature shows that the
co-morbidities of childhood obesity cover a large medical area ranging from
secondary hormonal disturbances to orthopaedic problems. Most of them have so far
been underestimated. However, the most severe problem of an obese child is his or
her psychosocial discrimination. Longitudinal data demonstrate a positive
relationship between childhood obesity and increased morbidity and mortality in
adulthood. CONCLUSION: Data from the literature are in some respect sparce since
they do not allow to calculate the exact prevalence of adverse effects nor to
assess the outcome of an obese child when it is successfully reducing the
relative amount of body fat.
PMID- 11011953
TI - Epidemiology of childhood obesity in Europe.
AB - At present, estimation of the prevalence and secular trends in paediatric obesity
in Europe is severely hampered by methodological problems in the definition of
obesity and the paucity of data sets that mirror the demographic, cultural and
socioeconomic composition of the European population. The available cross
sectional data, however imperfect, suggest that there are complex patterns in
prevalence which vary with time, age, sex and geographical region. Overall, the
prevalence of obesity in young children is relatively low compared to
adolescents. Gender differences in prevalence are inconsistent. The highest rates
of obesity are observed in eastern and southern European countries and even
within countries there may be marked variability in the rates of obesity. It is
not clear whether the trends in paediatric obesity are a simple consequence of an
overall increase in fatness in Europe or whether there may be sub-groups of
children who, at certain ages, are either particularly susceptible to
environmental challenges or are selectively exposed to such challenges. The
respective contributions of dietary energy intake and patterns of physical
activity to the aetiology of childhood obesity present a confused and confusing
picture. Changing demographic and social circumstances throughout Europe are
linked to childhood obesity but it is highly unlikely that these interact in
similar ways in the genesis of obesity in different individuals and population
groups. CONCLUSION: At present, our limited understanding of the variability in
susceptibility to obesity in European children and adolescents provides powerful
justification for the development of preventive strategies which are population
based rather than selectively targeted at high-risk children.
PMID- 11011954
TI - Aetiology of overweight and obesity in children and adolescents.
AB - The epidemic diffusion of obesity in industrialised countries has promoted
research on the aetiopathogenesis of this disorder. The purpose of this review is
to focus mainly on the contribution that European research has made to this
field. Available evidence suggests that obesity results from multiple
interactions between genes and environment. Parents obesity is the most important
risk factor for childhood obesity. Twin, adoption, and family studies indicated
that inheritance is able to account for 25% to 40% of inter-individual difference
in adiposity. Single gene defects leading to obesity have been discovered in
animals and, in some cases, confirmed in humans as congenital leptin deficiency
or congenital leptin receptor deficiency. However, in most cases, genes involved
in weight gain do not directly cause obesity but they increase the susceptibility
to fat gain in subjects exposed to a specific environment. Both genetic and
environmental factors promote a positive energy balance which cause obesity. The
relative inefficiency of self-adapting energy intake to energy requirements is
responsible for fat gain in predisposed individuals. The role of the environment
in the development of obesity is suggested by the rapid increase of the
prevalence of obesity accompanying the rapid changes in the lifestyle of the
population in the second half of this century. Early experiences with food,
feeding practices and family food choices affect children's nutritional habits.
In particular, the parents are responsible for food availability and
accessibility in the home and they affect food preferences of their children.
Diet composition, in particular fat intake, influences the development of
obesity. The high energy density and palatability of fatty foods as well as their
less satiating properties promotes food consumption. TV viewing, an inactivity
and food intake promoter, was identified as a relevant risk factor for obesity in
children. Sedentarity, i.e. a low physical activity level, is accompanied by a
low fat oxidation rate in muscle and a low fat oxidation rate is a risk factor of
fat gain or fat re-gain after weight loss. CONCLUSION: Further research is needed
to identify new risk factors of childhood obesity, both in the genetic and
environmental areas, which may help to develop more effective strategies for the
prevention and treatment of obesity.
PMID- 11011955
TI - Physical activity in relation to overweight and obesity in children and
adolescents.
AB - Fitness and physical activity levels of children and adolescents are commonly
addressed but data on scientific investigations are both equivocal and
methodologically diverse. The intensity and type of physical activity that
benefit health and development during childhood are not known. Measurement of
activity in children is problematic since there is no valid method of assessing
activity levels that is feasible for use in large field studies. Most studies
using self-report methods, heart rate studies using low heart rate threshold and
doubly labelled water studies indicate relatively high levels of activity in
children. The three national surveys on large representative samples reported
that 60% to 70% of all children were involved in sufficient physical activity
according to various definitions. Heart rate studies demonstrate that children
generally perform short bouts of moderate to vigorous activities and seldom
participate in long-sustained vigorous activities. They also proved that children
perform large volumes of activity in the lower heart rate zones. It is generally
accepted that boys are more active than girls and physical activity declines by
age (peak around 13 to 14 years of age). The difference between the physical
activity of European and North American children or between children living in
different European countries is difficult to judge due to the diversity of
methodology and definitions. CONCLUSION: There is a need to identify more clearly
the quantity and type of activity which improves the health and promotes the
normal development of children and to improve the methods assessing physical
activity.
PMID- 11011956
TI - Prevention and treatment of overweight and obesity in children and adolescents.
AB - Increasing numbers of obese children and adolescents all over the world demand an
investment in the primary and secondary prevention of obesity and overweight in
this age group. The goal of preventive measures in children is to avoid the
negative short- and long-term health problems associated with obesity. Primary
prevention aims at establishing a healthy, active lifestyle and keeping children
and adolescents within a range of body weight which is considered to be healthy.
Constant availability and affordability of palatable and energy-dense food in the
affluent society of the western world demands preventive strategies. Universal or
public health prevention seems to be the most suitable form because several other
cofactors of morbidity and mortality of affluent societies can also be prevented.
However, in most European countries there is a lack of awareness of the necessity
of prevention programmes, not only among the general population but also among
the medical society. More awareness and consciousness to the problem of obesity
must be generated in order to lead to effective therapeutic programmes. For those
children and adolescents who are already obese, secondary prevention is
mandatory. Therapeutic intervention programmes for the obese aim at long-term
weight maintenance and normalisation of body weight and body fat. They have to
modify eating and exercise behaviour of the obese child and establish new,
healthier behaviour and lifestyle. Treatments programmes must include behavioural
components in order to permanently change nutrition and physical exercise of the
obese children and adolescents. However, long-term results of treatment
programmes in European countries are scarce and the reported results, even of
multidisciplinary regimens, are not impressive. CONCLUSION: In most European
countries there is an urgent need not only for a growing awareness of the problem
of obesity in children and adolescents but also for development of new
comprehensive approaches in treating this group.
PMID- 11011957
TI - Androgen receptor--an update of mechanisms of action in prostate cancer.
AB - Androgen receptor (AR), a key nuclear transcription factor in the prostate gland,
is expressed in all histological types and stages of prostate cancer. The AR
regulates proliferation of prostate cancer cells by stimulation of cyclin
dependent kinases. However, in some prostate tumors AR stimulates expression of
cell cycle inhibitors, thus leading to down-regulation of cellular proliferation.
Androgens, by activation of the AR, control differentiation of prostate cells and
synthesis of neutral lipids. There are several mechanisms by which prostate
cancer cells adapt to an environment with low androgen supply during endocrine
therapy. The AR expression and activity increase in several cell lines that are
used as an in vitro model for monitoring changes during long-term androgen
ablation. Mutant ARs are of importance for monitoring the natural course of the
disease and for determining the response to anti-androgens in metastatic lesions
from prostatic carcinoma. In addition, AR activity is up-regulated by various
stimulators of intracellular protein kinases. Current research efforts are
focused on elucidation of function of AR coregulatory proteins, coactivators and
corepressors. Their inappropriate expression and/or function might critically
influence cellular events in advanced carcinoma of the prostate. It is hoped that
information on these coregulatory proteins will serve as a basis for a more
efficient pharmacological inhibition of the AR in advanced carcinoma of the
prostate.
PMID- 11011958
TI - Renal tubular apoptosis after complete ureteral obstruction in the presence of
hyperoxaluria.
AB - Hyperoxaluria is a well-known cause of renal stone disease and in vitro studies
have shown that oxalate crystals have a stimulatory effect on apoptosis of renal
tubular epithelial cells. Total and partial ureteral obstruction also have an
accelerating effect on apoptosis of renal tubular epithelial cells. The aim of
the present study was to investigate the apoptotic effect of unilateral ureteral
obstruction in the presence of hyperoxaluria on the rat kidney. Twenty-eight male
Wistar rats were divided into four groups, with seven rats in each. The groups
were named G1 (control), G2 (hyperoxaluric), G3 (obstructive) and G4
(hyperoxaluric + obstructive). G2 and G4 rats were given 1% ethylene glycol (a
precursor for oxalates) in their drinking water. G1 and G2 rats underwent sham
operation, while left proximal ureteral ligation with a 5-zero silk suture was
performed on G3 and G4 animals. The rats were sacrificed 2 weeks after the
operation; left nephrectomy was then performed. We searched for the apoptotic
cells by direct immuno-peroxidase detection of digoxigenin-labeled genomic DNA.
The mean +/- SD values of the apoptotic cell count was 0.86+/-0.90 in G1 and
4.33+/-3.81 in G2. The values for G3 and G4 were 30.17+/-16.85 and 302.67+/
184.45, respectively. We found a statistically significant difference between all
groups (P < 0.001). When compared with the control group (G1), the mean apoptotic
cell count was fivefold that of G2 and 35- and 351-fold those of G3 and G4,
respectively. Our study demonstrated that hyperoxaluria with complete ureteral
obstruction induces an excessive level of apoptosis, which is responsible for
renal damage, and that ureteral obstruction is a more important factor for
apoptosis than hyperoxaluria. Considering these data, we also believe that
research studies for medical preventive measures must be considered for patients
with ureteral obstruction and/or hyperoxaluria.
PMID- 11011959
TI - The role of estrogen receptor, androgen receptor and growth factors in
diethylstilbestrol-induced programming of prostate differentiation.
AB - Recently, others and we have demonstrated that prenatal exposure to an extremely
low dose of diethylstilbestrol (DES) and other estrogenic compounds produces a
significant effect on mouse prostate development in vivo and in vitro in the
presence and absence of androgen. In this study, we investigated the mechanism by
which DES produces this effect and determined the role of its estrogenic activity
on the growth and branching, induced by DES in the 17-day-old fetal prostate in
culture. Additionally, we investigated whether the androgen receptor (AR) plays a
role and whether any of the growth factors, namely, EGF and IGF-1 which are known
to modulate the estrogen receptor (ER) and androgen receptor (AR)-dependent
process, mediate the DES-induced effects. Using the organ culture bioassay of
prostate development, we demonstrate that DES enhanced the growth and branching
of the prostate at both 0.1 and 0.5 pg/ml dosages, thus, confirming a previous
report of ours. An anti-estrogen, ICI164,387 blocked both of the effect of DES,
suggesting that both of these two effects are ER dependent. Anti-androgen,
flutamide also blocked both branching and prostatic growth induced by DES, while
cyproterone acetate blocked only the branching effect, suggesting a role for AR
in the DES-induced effects. Depletion of EGF by anti-EGF antibody blocked the DES
induced effects and this was reversed following EGF replacement in the organ
culture system. Anti-IGF-1 antibody, on the other hand, only blocked the
branching effect, but produced no effect on the prostatic growth, induced by DES.
Estrogenic chemicals, bisphenol A and DES enhanced EGF-mRNA level of the cultured
prostates. Taken together, it appears that DES-induced prostatic enlargement
involves enhancement of ER-dependent EGF and IGF-1 synthesis, mediating prostatic
enlargement and androgen action.
PMID- 11011960
TI - Epidermal growth factor in urine from patients with bladder cancer.
AB - Epidermal growth factor (EGF), a mitogenic polypeptide with a molecular weight of
6000, is excreted in human urine in nanomolar quantities. Recently, some reports
showed that urothelial neoplasm was related to the concentration of EGF in urine.
In this study, EGF concentration in urine was measured by enzyme-linked
immunosorbent assay (ELISA) in 207 samples from 112 male patients (30-90 years
old, median 66.2) who had previously been treated for bladder cancer. Then, we
tried to clarify the significance of urinary EGF as a marker for recurrence of
bladder cancer in comparison with urine cytology. The samples were collected on
occasional follow up cystoscopy. Urine from nine age-adjusted males without
urological disease was also measured to obtain normal control values. In 123
samples from patients without tumors, EGF concentrations in urine decreased with
age. In 84 samples obtained from patients with recurrent tumor, EGF
concentrations were significantly lower than those in 123 samples from patients
without tumors (P < 0.001) Furthermore, EGF concentrations in longitudinal
samples collected the same patients during tumor recurrence and at the times when
no tumor was detected were measured in 56 patients. EGF concentrations in the
samples collected during tumor recurrence was significantly lower than that in
specimens collected when there was no tumor (P < 0.01). There were no significant
differences between the same samples collected during tumor recurrence with
regard to tumor grade, stage shape and number of tumors. However, EGF
concentration in urine from patients with carcinoma in situ (CIS) was lower than
that in specimens from patients without CIS. These results indicate the
usefulness of determining the EGF concentration as a marker for detecting bladder
cancer recurrence. Urine cytology was also examined in the same series and
findings were compared with those of urinary EGF. On cytology, class IV and V
were considered positive, and on urinary EGF, less than 10 ng/mgCr were
considered positive. Sensitivity was 25% for cytology and 57% for urinary EGF,
while specificity was 98% and 66%, respectively. The predictive positive value
was 0.88 and 0.53, respectively. With the combined use of urinary EGF and
cytology, the sensitivity, specificity and predictive positive value were 68%,
64% and 0.92, respectively. In conclusion, urinary EGF seems to be a useful
marker for detecting bladder cancer recurrence if performed in addition to
cytology. cancer recurrence if performed in addition to cytology.
PMID- 11011961
TI - Inhibition by vitamin C of DNA adduct formation and arylamine N-acetyltransferase
activity in human bladder tumor cells.
AB - Previous studies have already demonstrated the protective role of vitamin C
(ascorbic acid) in certain types of cancer. This study reports on the effects of
vitamin C on arylamine N-acetyltransferase (NAT) activity and DNA adduct
formation in a human bladder tumor cell (T24) line. The activity of NAT was
measured using high-performance liquid chromatography (HPLC), by assaying for the
amounts of acetylated 2-aminofluorene (AF) and p-aminobenzoic acid (PABA) and the
remaining amounts of AF and PABA. T24 cells were used for examining NAT activity
and carcinogen DNA adduct formation. The results demonstrated that NAT activity
and 2-aminofluorene DNA adduct formation in T24 cells were inhibited and
decreased by vitamin C in a dose-dependent manner. The apparent kinetic
parameters (apparent values of Km and Vmax) from T24 cells were also determined
with and without vitamin C cotreatment. The data also indicated that vitamin C
decreased the apparent values of Km and Vmax from T24 cells.
PMID- 11011962
TI - Epithelial mucin expression in bladder cancer: correlation with pathological and
clinical parameters.
AB - Recently, attention has been drawn to the role of polymorphic epithelial mucin
(PEM) as a possible target for cancer immunotherapy. To investigate the
expression of this molecule in bladder tissue, we used two mouse monoclonal
antibodies (HMFGI and HMFG2) raised against the core protein of the PEM. The
localization of these two anti-PEM antibodies was examined in normal (n = 10),
inflammatory (n = 10) and malignant (n = 67) bladder tissue samples with the use
of a three-step avidin-biotin method. For HMFG1 and HMFG2 localization was
successful in 78% and 60% of the bladder cancer samples, respectively, where as
they were localized only in 30% and 40% of normal bladder tissue samples,
respectively. Staining of either antibodies did not correlate with the grade,
stage, or survival of bladder cancer patients. We conclude that PEM is frequently
overexpressed by bladder cancer cells and HMFG1 is the antibody of choice to be
used as a carrier of a cytotoxic agent for application of intravesical targeted
therapy of bladder cancer.
PMID- 11011963
TI - First experience with gamma probe guided sentinel lymph node surgery in penile
cancer.
AB - Because of the curative approach, the detection of lymph node metastases in
squamous cell carcinoma (SCC) of the penis is of significant clinical relevance.
Sentinel lymph node (SLN) identification by means of lymphangiography has been
proven to be insufficiently safe. However, the high morbidity of inguinal
lymphadenectomy and the considerable individual variability regarding the
location of lymph node metastases justify the necessity of a technique that
enables the identification of SLNs. Since 1998, SLNs have been intraoperatively
identified and selectively dissected, after peritumoral injection of technetium
99m nanocolloid and using lymphoscintigraphy, in three patients (one with
malignant melanoma and two with SCC). At least one SLN could be detected in each
patient. The maximum surgical time was 30 min. There were no severe
complications. Lymph node metastases did not occur in any patient. Upon a mean
follow-up of 10 months, all patients are currently free of tumor. Owing to the
long-term results of sentinel lymphadenectomy in malignant melanoma of other
locations and our preliminary results with respect to penile carcinoma. we
consider the current method appropriate as the only primary operation for lymph
node staging in early stages and, in combination with modified inguinal
lymphadenectomy, in locally advanced stages.
PMID- 11011964
TI - An in vitro model for videoimaging of human bladder smooth muscle cell
contractions.
AB - Knowledge regarding human bladder smooth muscle cell (SMC) physiology is very
limited. Only a few specific medical therapies for bladder disorders have
therefore been established. The objective of this study was to develop a model
for videomicroscopy of bladder SMC contractions. Cells were isolated from human
cystoprostatectomy specimens and cultured in a modified EMEM medium. These cells
were identified as SMCs by means of immunohistochemistry. For videomicroscopy,
the culture flasks were coated with a viscous agent to allow cell contraction.
Contractions were visualized by means of a cell culture microscope with a time
lapse videosystem. For cholinergic stimulation of the cells, acetylcholine, in
concentrations ranging from 100 microM to 10 mM, was applied. The percentage of
contracting cells within the observation field was evaluated for quantitative
analysis. In control experiments without contractile stimulant 6% of the cells
were observed to contract. Stimulation with acetylcholine induced a significant
dose-dependent increase to 47% in contracting cells. These results demonstrated
that videomicroscopy is an appropriate tool to investigate the contraction
mechanisms of bladder SMCs. This model offers the possibility of studying drug
effects on the human detrusor in vitro.
PMID- 11011966
TI - The role of intracellular and extracellular calcium in mechanical and
intracellular electrical activity of human urinary bladder smooth muscle.
AB - We studied the role of extracellular and intracellular Ca2+ in human detrusor
smooth muscle contraction. Simultaneous recordings of mechanical and
intracellular electrical activity were made in three different Ca2+
concentrations: normal Krebs' solution (100%), 10% of the standard Ca2+
concentration and a solution in which Ca2+ was omitted from the medium (0%).
Spontaneous contractions and KCl or CCh induced contractions were studied.
Ryanodine and caffeine were used to manipulate the intracellular Ca2+ stores. The
present results show that only a very small amount of Ca2+ in the extracellular
space is sufficient to support spontaneous and induced contractions. Spike-shaped
potentials and long lasting depolarisations were recorded in all three solutions.
However, the prevalence of long lasting depolarisations increased when the
extracellular Ca2+ concentration was reduced. The amplitude of the spike-shaped
potentials and long lasting depolarisations appeared to be negatively affected by
diminishing the extracellular Ca2+ concentration. Additionally, the duration of
the long lasting depolarisations was reduced in 0% Ca2+. The contraction upon KCl
stimulation was primarily depending on the extracellular Ca2+. Upon muscarinic
receptor stimulation, a combined activation of Ca2+ mobilisation from
intracellular and extracellular stores may occur; the ratio of contribution of
these two sources changes in accordance with the requirements of the conditions.
PMID- 11011965
TI - Inhibition of diabetic bladder smooth muscle cell proliferation by endothelin
receptor antagonists.
AB - Urinary bladder hypertrophy and hyperplasia are well recognised in diabetic
cystopathy. The urinary bladder is known to synthesise endothelin-1 (ET-1), a
potent vasoconstrictor peptide with mitogenic properties. Using diabetic New
Zealand White (NZW) rabbits, we investigated the potential role of ET receptor
subtypes (ETA and ET(B)) on the proliferation of bladder smooth muscle cells
(SMC). Diabetes mellitus was induced in adult male NZW rabbits. After 6 months,
control (n = 6) and diabetic (n = 6) bladders were removed and SMC from the dome
and bladder neck were grown using standard explant methodology. At passage two,
the cells were made quiescent and then further incubated in foetal calf serum
(FCS), control age-matched rabbit serum (CRS) or diabetic rabbit serum (DRS) in
the presence or absence of ET(A)-antagonist (BQ123) or ET(B)-antagonist (BQ788).
SMC proliferation was then measured with 5-bromo-2'deoxy-uracil 24 h later and by
cell counting (using a haemocytometer) at 48 h. Neither BQ123 nor BQ788
influenced detrusor or bladder neck SMC proliferation in FCS or CRS. However, in
the presence of DRS, BQ123 and BQ788 significantly inhibited diabetic detrusor
and bladder neck SMC proliferation at 30 and 100 nmol/l (P < 0.03 and P < 0.01,
respectively). Cell counts were also significantly reduced from the diabetic
detrusor and bladder neck (P < 0.01 and P < 0.03 with BQ123 and BQ788,
respectively). These results suggest that ET may play a pathophysiological role
in the bladder SMC hyperplasia associated with diabetes mellitus.
PMID- 11011967
TI - Determination of mouse bladder inflammatory response to E. coli
lipopolysaccharide.
AB - Evaluation of the severity of histologic changes associated with cystitis is
often subjective and inconsistent from one sample to the next. The objective of
this study was to establish a consistent, reproducible method to quantify
histologic changes in a mouse model of lipopolysaccharide (LPS)-induced cystitis.
Either LPS (n = 8) or pyrogen-free saline (n = 8) was instilled intravesically
into the bladders of female C57bk-6 J mice. Twenty-four hours later, mice in
these groups as well as eight untreated controls were sacrificed and bladders
were removed, fixed in formalin, and stained with hematoxylin and eosin (H&E). A
bladder inflammatory index (BII) was described by reviewing tissues for edema,
leukocyte infiltration, and hemorrhage. Cross-sections were evaluated by a single
pathologist in a blinded manner based on the objective BII described. The BII
method for objectively analyzing bladder inflammation was effective and
reproducible. Bladders instilled with LPS had significantly increased
inflammation scores for edema, leukocyte infiltration, and hemorrhage compared
with those instilled with saline or untreated controls (n = 8, P < 0.05). These
results demonstrate that LPS causes bladder inflammation when instilled
intravesically and that inflammation of mouse bladders can be objectively
quantified using the histological method described.
PMID- 11011968
TI - A new approach to calculate the risk of calcium oxalate crystallization from
unprepared native urine.
AB - This work focuses on the in vitro calcium-oxalate (CaOx) crystallization
behaviour of native and synthetic urine samples in order to establish a CaOx
crystallization risk index for unprepared native urine. Native 24-h urine samples
from healthy persons and from stone-formers were examined. Within a [Ca2+] versus
added oxalate (Ox2-) diagram, we observed fields which allow the discrimination
of each urine sample in terms of more or less risk. The [Ca2+]/(Ox2-) ratio is
calculated and termed the "Bonn-Risk Index" (BRI; per litre). We propose that
BRIs > 1/l denote samples "at risk", whereas BRIs < or = 1/l denote those
"without risk". Second. the effects of different concentrations of citrate and
Mg2+ on BRI were investigated in artificial urine. The transferability of BRI
between native and synthetic urine samples is proved. To evaluate the impact of
the proposed BRI, it is compared with the more familiar relative urine saturation
index calculated for CaOx and brushite. Urine sampled from stone-formers shows
risk indexes between 0.278 and 23.0/l (mean 2.87/l), while urine from healthy
persons varied between 0.060 and 4.890/l (mean 1.05/l). Comparing the results of
healthy volunteers and patients, the significance of BRI and relative urine
supersaturation (RS) with respect to CaOx is P < 0.0005 and P = 0.013,
respectively. Fast and easy to perform, determination of the risk index is a
suitable tool for estimating the actual CaOx formation "status"--"at risk" or
"without risk"--from the native urine of any person.
PMID- 11011969
TI - Poor semen quality from patients with malignancies does not rule out sperm
banking.
AB - Cancer therapy can further impair the already poor semen quality in cancer
patients. This study evaluated the prefreeze and postthaw semen quality before
treatment of patients with malignancies to examine the rationale for sperm
banking for these men. Records of nine patients with different malignant tumors,
who had been referred for sperm cryopreservation between 1982 and 1997, were
reviewed and the results were compared with those of 50 normal healthy donors.
Patients did not differ from donors in age, ejaculate volume, or duration of
sexual abstinence. The total motile sperm count (median and interquartile range)
was significantly different between patients and donors for prefreeze specimens
(P = 0.026) and postthaw specimens (P = 0.008). Also, the percent motility was
significantly lower in the patients as compared with the donors in prefreeze (P =
0.035) and postthaw specimens (P = 0.005). The percentage change in motility
after thawing was also larger for patient samples (-54% versus -47%, P = 0.39).
Other sperm motion characteristics did not significantly differ between the two
groups except for postthaw curvilinear velocity (P = 0.01). This study concludes
that fresh and frozen thawed semen from patients with malignant tumors is poor in
quality but is still adequate for assisted reproductive techniques. As cancer
therapy may further impair semen quality, patients should be offered the chance
to bank sperm before undergoing cancer therapy.
PMID- 11011970
TI - Frontal lobe tasks do not reflect frontal lobe function in patients with probable
Alzheimer's disease.
AB - Thirty-one patients with probable Alzheimer's disease (AD) according to NINCDS
ADRDA criteria were psychometrically tested with various frontal lobe tasks. The
results were correlated with regional cerebral glucose metabolism (rCMRG1) as
measured by positron emission tomography of 18F-2-fluoro-2-deoxy-D-glucose.
RCMRG1 of frontal functional-anatomically defined regions was not linked to the
performance seen in frontal lobe testing. The majority of the frontal lobe tasks
showed a high correlation to severity of dementia that was related to rCMRG1 of
the temporo-parietal cortex. There were high intercorrelations of frontal lobe
test scores to other tests. Thus, these tasks seem to measure nonspecific
cognitive changes in AD patients.
PMID- 11011971
TI - Hoffmann reflex profiles and strength ratios in postoperative anterior cruciate
ligament reconstruction patients.
AB - Rupture of the anterior cruciate ligament (ACL) typically leads to surgical
reconstruction followed by an extensive rehabilitation program. One of the most
commonly experienced complications associated with ACL rupture and reconstruction
is quadriceps muscle atrophy. A clear understanding of the exact mechanisms
associated with ACL related atrophy remains undocumented. The purpose of the
present study was to investigate maximum H-reflex to maximum M-wave ratio as well
as quadriceps deficit for both isometric and isokinetic peak torques in a post
ACL reconstruction population. Forty subjects volunteered for participation in
this study. The experimental group comprised 20 subjects who had undergone
patellar tendon graft reconstruction of a torn ACL. A matched control group of 20
subjects were also measured for comparative purposes. The results indicated the
control group had significantly higher quadriceps to quadriceps ratio than did
the ACL group [t(38) = 9.05 p < .001]. In contrast, there was no difference in
the H-max/M-max ratio for either group or leg. The strength findings of this
study support previous findings. The spinal reflex results support the need for
additional research in this area, specifically with more acutely injured
subjects.
PMID- 11011972
TI - Dynamic systems theory approach to consciousness.
AB - The review of the main existing approaches to consciousness in the literature
indicates that consciousness is multileveled and that humans have an ability to
experience a wide range of its various states. The common views of the main
approaches to consciousness are identified and considered in a three-dimensional
model of states of consciousness developed by Kokoszka. This model is then
described and discussed using a mathematical terms of dynamic systems theory.
Since mathematics is an accepted tool for the description of the physical world,
the congruence of psychological and mathematical models is understood as a
meaningful support to the psychological one. Connections of the models with
artificial neural networks and some applications in psychology are considered.
PMID- 11011973
TI - The perception of rorschach inkblots in schizophrenia: a neural network model.
AB - Schizophrenia is a psychiatric disorder characterized by a variety of cognitive
deficits, including perceptual distortions and hallucinations. In recent years
several studies have proposed that schizophrenia may involve a disturbance of
"context". We have used a three layer neural network model constructed from an
input layer followed by two computational layers to simulate responses of
schizophrenic patients to the Rorschach test. In this test subjects respond to a
set of ambiguous patterns created by ink blots on paper. Our model proposes that
a disturbance of context caused by altered noise-to-signal ratio at the level of
the single units, is responsible for schizophrenic responses to the Rorschach
test. The assumption that catecholaminergic neurotransmitter systems regulate
noise-to-signal ratio in cortical neurons constitutes a link between findings of
altered neurotransmitter activity and deficits of cognitive functions requiring
contextual integration in schizophrenia. The development of models for specific
task deficits in schizophrenia could advance our insights regarding the
neurological mechanisms underlying serious mental disorders such as
schizophrenia.
PMID- 11011974
TI - The effects of melatonin on the antioxidant systems in experimental spinal
injury.
AB - Melatonin has been recently shown by various in-vivo and in-vitro studies to
exert potent neutralising effects on hydroxyl radicals, stimulate glutathione
peroxidase (GSH-Px) activity, and protect catalase (CAT) from the destructive
activity of hydroxyl radicals in neural tissue. We aimed to investigate the
possible effects of pharmacological dose of melatonin on some of the antioxidant
defence systems in an in-vivo study of experimental spinal injury. Seven groups
of adult male Sprague Dawley rats were used in the following scheme: Group I:
Naive (n = 6), Group II: Lesion (n = 8), Group III: Melatonin (n = 5), Group IV:
Melatonin + Lesion (n = 8), Group V: Placebo + Lesion (n = 5), Group VI: Sham
operation (n = 5), and Group VII: Placebo (n = 5). Experimental spinal injury was
induced at level T7-T8 by 5 sec compression of the total cord with an aneurysm
clip on anaesthetised and laminectomized animals. The total 10 mg/kg dose of
melatonin (Sigma) dissolved in alcohol-water was administered i.p. four times in
2.5 mg/kg doses, at 20 min pre-, at the time of and at 1 h and 2h post
compression. At 24 +/- 2h post-injury, the rats were euthanized and the lesioned
segments of cord were dissected and homogenised with special care taken to
distribute equal amount of injured tissue in each sample for analysis of reduced
glutathione (GSH), oxidised glutathione (GSSG), superoxide dismutase (SOD), and
CAT activity. Compression injury decreased GSH/GSSG ratio significantly (p <
.0001). Melatonin, by itself, significantly decreased GSSG content (p < .05) and
increased CAT activity (p < .05) in the naive rats. Melatonin treatment decreased
GSSG activity, thus elevating GSH/GSSG ratio, and also increased SOD and CAT
activity without reaching statistical significance in the lesioned animals. In
conclusion, pharmacological dose of systemically applied melatonin seemed to
support some features of the antioxidant defence systems in our hands.
PMID- 11011975
TI - Probability and interstimulus interval effects on the N140 and the P300
components of somatosensory erps.
AB - Event-related potentials (ERPs) evoked by somatosensory stimuli were studied in
two experiments with manipulation of the interstimulus interval (ISI) in the
range from 1 to 4 seconds and the stimulus probability from 10 to 50% in fine
steps. All the stimuli were presented randomly on both index fingers as odd-ball
paradigm, and the stimulus intensities on both sides were equally set at 2.5
times the subjective sensory threshold at which the stimuli could easily be
ignored when delivered as nontarget stimuli. During the course of two
experiments, the N140 was evoked by the target and nontarget stimuli, otherwise
the P300 was evoked by the target stimuli alone. In the experiment on the effects
of ISIs change, the N140 amplitude showed a tendency to increase with increasing
ISI and the P300 amplitude increased with increasing ISI. In the other experiment
on the effects of change in stimulus probability, the amplitudes of both the N140
and the P300 decreased with increasing stimulus probability. From the results
across two experiments. it is argued that the effects of both probability and ISI
changes on the amplitudes of both the N140 and the P300 do not directly reflect
the recovery time of psychological functions but may also involve the complicated
effects derived from the habituation of the individual generators and the
difficulty for performing the task. Moreover, it is indicated that the stimulus
intensity used is one of major factors to be considered for comparing results to
discuss the effects of ISI and probability on the ERPs.
PMID- 11011976
TI - Somatosensory evoked potentials associated with thermal activation of type II
Adelta mechanoheat nociceptive afferents.
AB - We evaluated evoked potentials (EPs) to noxious contact heat pulses delivered to
hairy skin of healthy adults. Heat pulses from an adapting temperature of 34
degrees C to a target temperature of 52 degrees C, produced two scalp positive
waves. The first peaked at 44 degrees to 45 degrees C (approximately 500 ms
following stimulus onset), while the second peaked approximately 300 ms following
the 52 degrees C heat pulse (approximately 1 s after stimulus onset). The first
positive wave was absent from an adapting temperature of 39 degrees C, suggesting
loss of synchronized activation of warm and/or low threshold mechanothermal
afferents. The second EP was observed following stimulation from both adapting
temperatures and was associated with subjective report of first pain. Latency
difference of the pain EP from arm and leg were consistent with conduction in
Adelta nociceptive afferents (approximately 10/ms). EPs to painful contact
thermal stimuli may be of value in the evaluation of small fiber peripheral
neuropathies and assessment of altered pain states.
PMID- 11011977
TI - The relationship of neuropsychological functioning to measures of substance use
in an adolescent drug abusing sample.
AB - The purpose of this research was to investigate the relationship between recent
and long term substance use on adolescents' neuropsychological functioning.
Subjects were 77 adolescents who were referred for outpatient treatment for drug
and conduct problems. Subjects were administered the Luria-Nebraska
Neuropsychological Battery-III, structured interviews to assess substance use,
and urine tests. Subjects were divided into neuropsychologically impaired and
nonimpaired groups. Results indicated no significant group differences for: self
reports of lifetime use of alcohol, cannabis, and hard drugs; self or collateral
reports of recent (past 30 days) use of alcohol, cannabis, and hard drugs; or
urinalysis detection of alcohol, cannabis, and hard drugs. Correlations between
these dependent measures of substance use and neuropsychological functioning were
also nonsignificant (all ps > .05). Although neuropsychological impairment was
observed for some subjects in this sample, it was unrelated to their cannabis,
hard drug, or alcohol use. These results are consistent with those found in the
adult literature, given the relatively short period of time that these youth have
used such substances. However, given the severity of their absolute levels of
substance usage, they may be at greater risk for developing future
neuropsychological problems, related directly to the ingestion of alcohol and
illicit drugs, and to their secondary effects (e.g., head traumas, malnutrition).
PMID- 11011978
TI - Factor structure of nonverbal cognition.
AB - In order to define the factor structure of nonverbal cognitive processes, 156
twenty to sixty year-old participants were selected in Medellin (Colombia). A
neuropsychological test battery for assessing different nonverbal cognitive
domains (attention, memory, visuoperceptual and visuoconstructive abilities.
executive functions, praxis abilities, and written calculation abilities) was
administered. Initially, independent factor analyses were carried out for each
domain. Three attention factors (Sustained Attention, Divided Attention, and
Processing Speed, 73.1% of the variance); two memory factors (Categorical and Non
Categorical Memory, 59.7% of the variance): two visuoperceptual and
visuoconstructive factors (Sequential and Simultaneous, 54.0% of the variance);
and two executive function factors (Categorization and Trial Error, 82.0% of the
variance) were found. Further, several sequential factor analyses using Varimax
orthogonal rotations for noncorrelated variables were performed. The 32 test
variables were included, but progressively some variables were removed. This
procedure finally selected 13 variables corresponding to five factors accounting
for 72.6% of variance. Factor I was an Executive Function factor (30% of
variance). Factor 2 corresponded to a Sequential Constructional factor (14.7%).
Factor 3 represented a Processing Speed factor and accounted for 10.6% of the
variance. Factor 4 was Visuoperceptual factor (9.5% of the variance). Finally,
Factor 5 (7.8% of the variance) was a Nonverbal Memory factor. It was concluded
that several, different cognitive dimensions are included in nonverbal cognition.
PMID- 11011979
TI - Quantitative correlation between initial dissolution rate and heat of fusion of
drug substance.
AB - The initial dissolution rates of amorphous, partial crystalline and crystalline
samples of terfenadine polymorphs (forms I and II) were measured by the rotating
disk method. The heats of fusion due to crystalline fraction of samples were
obtained by the differential scanning calorimetry (DSC) data taking into account
the heat of crystallization and the heat capacity change at glass transition
during the heating process. The logarithms of initial dissolution rates of
different crystallinity samples were linearly correlated with the corrected heats
of fusion, irrespective of the crystal forms.
PMID- 11011980
TI - Preparation of enteric coated timed-release press-coated tablets and evaluation
of their function by in vitro and in vivo tests for colon targeting.
AB - As a new oral drug delivery system for colon targeting, enteric coated timed
release press-coated tablets (ETP tablets) were developed by coating enteric
polymer on timed-release press-coated tablets composed of an outer shell of
hydroxypropylcellulose and core tablet containing diltiazem hydrochloride (DIL)
as a model drug. The results of the in vitro dissolution tests in JP 1st fluid
(pH 1.2) and JP 2nd fluid (pH 6.8) indicated that these tablets showed both acid
resistance and timed-release. To clarify whether ETP tablets could have been of
use in the gastrointestinal tract, ETP tablets with a layer of
phenylpropanolamine hydrochloride (PPA) (a marker of gastric emptying) between
the enteric coating layer and outer shell were prepared, and were administered to
beagle dogs. The gastric emptying time and lag time after gastric emptying were
evaluated by determining the times at which PPA and DIL first appeared in the
plasma (TFA(PPA) and TFA(DIL), respectively). TFA(PPA) and TFA(DIL) were about 4
and 7 h, respectively. This value of TFA(PPA) indicated that ETP tablets
displayed acid resistance in the stomach as well as in JP Ist fluid. Subtraction
of TFA(PPA) from TFA(DIL) gave a value of about 3 h which agreed well with the
lag time determined by in vitro dissolution test in JP 2nd fluid. Also, the
results seemed to be in accordance with the time at which the tablets reached the
colon after gastric emptying. Therefore, ETP tablets seemed to be an effective
tool for oral site-specific delivery including targeting of the colon.
PMID- 11011981
TI - Determination of plasma concentrations of losartan in patients by HPLC using
solid phase extraction and UV detection.
AB - PURPOSE: To establish a HPLC assay for plasma losartan and its active metabolite
EXP3174 to facilitate clinical pharmacokinetic studies. METHODS: the HPLC system
consisted of a 250 x 2 mm i.d. C18 reversed phase column preceded by a 4 x 4 mm
guard column, a UV detector set at 254 nm, and an integrator. The mobile phase
was a mixture of 0.01 M ammonium phosphate: acetonitrile: methanol (6:3:1)
containing 0.02 % sodium azide and 0.04% TEA, with pH adjusted to 3.2. The system
was operated isocratically at ambient temperature at a flow rate of 0.3 ml/min.
Losartan and its active metabolite EXP3174 were extracted from plasma using C2
bonded silica gel standard solid phase extraction. RESULTS: recoveries of
losartan and EXP3174 from plasma were greater than 70%. Using 0.5 ml of plasma
sample, standard curves were linear from 10 to 300 ng/ml (r2 = 0.996 and 0.997
for losartan and EXP 3174, respectively). Sensitivity of the assay was < 10
ng/ml. Intra-and inter-assay variations were < 10 and 15%. respectively. The
assay has been successfully applied to measuring plasma concentrations of
losartan and EXP3174 in patients receiving a daily dose of losartan (50-100 mg).
CONCLUSION: The HPLC assay has adequate sensitivity, reproducibility, and
specificity for clinical pharmacokinetic studies.
PMID- 11011982
TI - Plasticisation of amylodextrin by moisture: consequences for drug release from
tablets.
AB - Moisture influences the consolidation behaviour of amylodextrin powders and the
porosity and mechanical strength of compacts thereof. The aim of this study is to
relate moisture content and compact properties to drug release characteristics of
amylodextrin tablets. Therefore, amylodextrin tablets containing theophylline
monohydrate were prepared and their release characteristics were studied as a
function of moisture content and initial porosity. Drug release from amylodextrin
tablets occurs through a leaching mechanism in which cracks are progressively
formed in the hydrated part of the matrix leading to almost constant release
rates. Small variations in moisture content resulted in large changes of the
release rate. A unique relationship between porosity and release rate, which was
independent on moisture content and compaction pressure, was observed. Above a
critical porosity of 0.075 crack formation was followed by disintegration and
fast release. Below this critical porosity, tablets stayed intact despite of the
formation of cracks, and sustained release was observed. It is concluded that
control over moisture content is essential for the production of amylodextrin
tablets with reproducible release characteristics. Using amylodextrin containing
10-17%, moisture, tablets with a constant release behaviour can be obtained if
sufficient compaction pressure ( > 300 MPa) is applied. Lubrication of
amylodextrin powders reduces the effect of porosity significantly and improves
the robustness of amylodextrin tablets as a release controlling excipient in
tablets largely.
PMID- 11011983
TI - Intranasal administration of different liquid formulations of bumetanide to
rabbits.
AB - The bioavailability of bumetanide in rabbits after intranasal administration of
eight formulations intended for use in acute situations has been studied. The
vehicles tested were combinations of phosphate buffer, pH 7.4, glycofurol 75.
polyethylene glycol 200 and coconut oil. A mixture of 51% glycofurol in
polyethylene glycol 200 was administered containing doses of 1 and 8 mg
bumetanide respectively. For all other formulations the lower dose level only was
studied. The tmax obtained ranged from 3 to 10 min. The vehicles resulting in the
highest rate of absorption were 60% glycofurol in coconut oil and pure
glycofurol. The observed bioavailability for the different formulations ranged
from 16 to 37% for the time period 0-120 min. The bioavailability was also
calculated omitting the initial peak seen after i.v. injection, which may be
undesirable. Using this method bioavailabilities of 33-82, for the time interval
5-120 min was found. The study also demonstrated that the total amount of
bumetanide absorbed increased proportionally to the dose administered. The rate
of absorption of bumetanide from all formulations tested may be relevant for the
treatment of acute oedematous states. The tmax obtained after intranasal
administration was shorter than reported for other non-parenteral routes of
administration.
PMID- 11011984
TI - Fabrication of oral acid resistant Fermosorb (Ferment + sorbent)-type
preparations can be simplified using industrial Bacillus subtilis culture
filtrates as an enzyme source.
AB - In our recent article [Biziulevicius, G.A. and Zukaite, V., 1999. Int. J. Pharm.
189, 43-55] we described a novel approach in design of oral preparations intented
for intestinal delivery of enzymes, based on reversible immobilization of the
latter onto the polymer matrix. Fermosorb (ferment + sorbent)-type preparations,
produced in such a way, are characterized as two-component delayed-release enzyme
formulations being stable at acidic pH and thus ensuring the protection of an
active substance in the environment of the gastric region and liberating the
active substance through dissociation of the enzyme-polymer complex at neutral pH
values characteristic for the intestines. In the present paper we report our
updated findings showing that the technology of fabrication of two Fermosorb-type
preparations manufactured (namely Fermosorb and Polyferm) can be simplified (as
well as their production cost reduced) substituting the acetone precipitated
enzyme preparation solutions, currently used as an enzyme source, by their
precursors--industrial Bacillus subtilis culture filtrates. Moreover, we give a
description of how one more Fermosorb-type preparation aimed at intestinal
delivery of amylolytic enzymes can be produced in a similar manner. Determination
of immobilization conditions has revealed, that irrespectively of the enzyme
origin (lytic, proteolytic or amylolytic) and its source (1%, acetone
precipitated preparation solution or culture filtrate), optimal for
immobilization v/w ratio of the liquid phase and the polymer matrix (Biocarb L)
remains the same and is equal to 10:1 (approximate). The main differences have
been found to be in optimal for immobilization pH values as well as process
duration in regard to the two enzyme sources applied. In case of proteolytic and
amylolytic enzymes only one of the variables was different (process duration for
the first ones, optimal pH for the second ones), while in case of lytic enzymes
both variables were different. The percentage of the enzymes activity uptaken
from the reaction mixture formed by either of the enzyme sources and the polymer
matrix (approximately 60%) as well as activity losses at drying the enzyme
polymer complexes ( approximately 20%), tolling in the final activity yield of
near 40%, were found to be very similar.
PMID- 11011985
TI - Effect of dosing time on the total intestinal transit time of non-disintegrating
systems.
AB - The total gastrointestinal transit time of nondisintegrating tablets may be
affected by dosing time; available literature on this topic is inconclusive. OROS
systems are nondisintegrating osmotically driven tablets that release drug over a
period of time during their transit through the gastrointestinal tract and are
excreted intact in the feces. Total transit times following morning
administration of OROS systems pooled from various studies (n = 1,163 systems)
showed a distribution with peak frequencies clustering around 24 and 48 h and
following night administration (n = 80 systems) was found to cluster around 12
and 36 h. The total transit time distribution appears to be different following
morning and night administration. However, on reanalyzing the data considering
clock time when the tablet was collected rather than time post-administration,
most of the difference between the distribution patterns disappeared. This
suggested that total transit times after morning or night administration may be
related to the bowel movement habits of the study population. Therefore, OROS
systems total transit time were compared to the intrinsic bowel movement pattern
of the general population reported in the literature and indeed a good
correlation was seen between the two. The total transit time appears to be
determined by two factors: the defecation frequency and the probability of its
inclusion in the defecation event which is related to its location in the GI
tract. A tablet is more likely to be excreted if it is further down in the GI
tract. The total transit time data for OROS systems suggest that with the morning
dosing the tablet is more likely to be excreted in the bowel movement the next
morning. With the night time dosing the tablet may not be far enough in the colon
to be excreted in the next morning bowel movement and therefore, it is more
likely to be excreted the following morning.
PMID- 11011986
TI - Application of acid-treated yeast cell wall (AYC) as a pharmaceutical additive I.
AYC as a novel coating material.
AB - Acid-treated yeast cell wall (AYC) was newly prepared by acidifying the cell wall
of brewer's yeast and the potential to use AYC as a novel coating material was
studied. AYC had an oval shape with the diameter of several microm. The rheogram
of AYC aqueous dispersion showed the plastic fluid property that is generally
observed in the suspension. Core tablets containing 3% of acetaminophen (AAP)
were coated with the AYC aqueous dispersion containing 5% (w/v) of AYC and 0.35%
(w/v) of glycerol at various coating percents. The AAP release profile from the
AYC-coated tablets was studied by the JP13 paddle method using solutions at
various pH. Tensile strength and permeability of oxygen and water vapor of AYC
cast film were measured. The AAP release from the AYC-coated tablets showed
sigmoidal release profile with an initial lag time and the duration of the lag
time depended on the coating percent of AYC. The pH of the dissolution fluid or
the storage at room temperature for 120 days had little affect on AAP release
from the AYC-coated tablets. These results suggest that it is possible to control
the start time of medicine release independent of the pH by coating of AYC, that
is the time-controlled release. The AYC cast film showed a large tensile strength
and an extremely small oxygen permeability coefficient and a sufficient level of
water permeability coefficient in order to protect from moisture. These results
present that AYC has the high utility as a novel aqueous coating material for DDS
preparations.
PMID- 11011987
TI - Statistical assessment of between batch stability equivalence.
AB - A statistical method for testing the equivalence between batches regarding their
stability is proposed. This method is based on the statistical linear model
making use of a set of dummy variables to code the different batches. The method
gives us the point estimates of the slope and zero intercept of one batch, and
the differences and the corresponding confidence intervals with the remaining
batches. In a second step, zero intercepts and slopes are estimated for all the
batches. Stability equivalence assessment is based on the comparison of the
confidence intervals for the differences between batches with the maximum
difference allowable. The main advantages of this method are the possibility to
compare several batches, to disclose the equivalence stability criteria from the
statistical hypothesis about the equality between slopes, and the joint estimated
of the residual variance whatever the decision to pool or not the data from
different batches. This method is illustrated with two data set; the first one,
previously published by other authors, involved six batches; the second data set
include two batches and arose in a stability study of a commercial human insulin
conducted in our laboratory.
PMID- 11011988
TI - An investigation of some of the factors influencing the jet nebulisation of
liposomes.
AB - Multilamellar egg phosphatidylcholine liposomes with or without cholesterol have
been aerosolised using four jet nebulisers. The size of aerosols generated from
liposome suspensions, as measured by laser diffraction, was independent of
liposome size and bilayer composition. However, increasing the phospholipid
concentration caused an increase in the median size of the secondary aerosol
size, although the extent of this effect was dependent on the design on the
nebuliser. The total mass output of liposomal aerosols was similar for the Pari
LC and Sidestream nebulisers, though the rate of output was higher for the
Sidestream. In both cases, increasing lipid concentration produced a reduced rate
of aerosol output. For all the nebulisers studied, a size selective process was
found, resulting in the retention of the largest liposomes.
PMID- 11011989
TI - Characterization and in vitro release of methotrexate from gelatin/methotrexate
conjugates formed using different preparation variables.
AB - The purpose of this study was to evaluate effects of preparation variables on the
composition of gelatin-methotrexate conjugates, and to evaluate their in vitro
stability. Conjugation variables of pH, amount of conjugating agent 1-ethyl-3
(diaminopropyl)carbodiimide HCl (EDC), and methotrexate (MTX), with
unfractionated gelatin were examined. Conjugate composition was determined
spectrophotometrically. The molar ratios of MTX to gelatin in the conjugates
ranged from 5.9 to 64.9. Molar ratios increased with molecular weight (MW) of
gelatin in the conjugate, but the weight ratio was constant. This common
conjugating procedure, however, produces by-product crosslinking and produces a
mix of covalent MTX binding to carboxyl and amino groups of the gelatin. For
release studies, gelatin was fractionated by size exclusion spectra (SEC) into MW
of 21, 91, and 195 kDa prior to conjugation. MTX release from conjugates in
dialysis cassettes at 25, 37, and 50 degrees C, in isotonic pH 7.4, buffer over
72 h was assayed by high performance liquid chromatography (HPLC). There was no
effect of gelatin MW on MTX release. MTX release was approximately linear and
attained 2.3, 7.2, and 13% by 72 h at 25, 37, and 50 degrees C, respectively, for
the 91 kDa conjugates. First-order release rate constants were 0.23 x 10(-3),
0.95 x 10(-3), and 1.8 x 10(-3) x h(-1), respectively. The calculated activation
energy for MTX release was 15.8 kcal/mol. Rate constants and the activation
energy for MTX release are consistent with hydrolysis of a peptide bond. Non
degraded MTX species were found in the release medium at amounts similar to free
MTX and were attributed to MTX polymers and MTX/gelatin fragments < 10 kDa.
PMID- 11011990
TI - Penetration of topical and oral ofloxacin into the aqueous and vitreous humor of
inflamed rabbit eyes.
AB - PURPOSE: This study aimed to investigate the penetration of topical and oral
ofloxacin into aqueous humor and vitreous humor in post-traumatic endophthalmitis
model in rabbits. METHODS: A standardized intraocular infection after penetrating
injury was made in the right eyes of 16 rabbits. Intraocular infection was
induced by intravitreal injection of a suspension of Staphylococcus aureus. The
intact left eyes were maintained as controls. The animals were divided randomly
into two groups. (1) In the topical group, two drops of ofloxacin 0.3% eyedrops
were instilled to both eyes every 30 min for 4 h. (2) In the topical-oral group,
two doses of 25 mg/kg of ofloxacin at 12-h intervals were given orally, then the
protocol of the first group was applied. Aqueous and vitreous humor samples were
taken 30 min after the last drop. Ofloxacin concentrations were measured by using
HPLC. RESULTS: Mean aqueous levels of ofloxacin in control eyes were: 3.25 +/-
2.55 microg/ml in topical group. 4.58 +/- 5.39 microg/ml in topical-oral group.
Mean aqueous levels in inflamed eyes were: 5.21 +/- 4.55 microg/ml in topical
group, 10.34 +/- 8.88 microg/ml in topical-oral group. Mean vitreous levels of
ofloxacin in control eyes were: 0.17 +/- 0.07 microg/ml in topical group, 1.30 +/
1.23 microg/ml in topical-oral group. Mean vitreous levels in inflamed eyes
were: 0.35 +/- 0.22 microg/ml in topical group, 3.48 +/- 2.69 microg/ml in
topical-oral group. There was no significant difference among the groups (P >
0.05), however. CONCLUSIONS: The result of this study suggests that oral
supplementation of ofloxacin to topical instillation increased the ocular levels
of ofloxacin in the post-traumatic endophthalmitis model. Mean drug
concentrations in aqueous and vitreous humors were above the 90% minimum
inhibitory concentrations (MIC90) for most of the common microorganisms causing
endophthalmitis in all eyes, except in the vitreous humors of the intact eyes
instilled topically.
PMID- 11011991
TI - The effects of prolonged acute use and inflammation on the ocular penetration of
topical ciprofloxacin.
AB - PURPOSE: To study the aqueous and vitreous penetration of ciprofloxacin after
prolonged acute topical administration and to investigate the effects of
inflammation on drug penetration. METHODS: A standardized model of intraocular
infection after penetrating injury was made in the right eyes of eight rabbits.
The intact left eyes were maintained as the control. Two drops of ciprofloxacin
0.3% eyedrops were instilled topically every 1 h for 7 h to all eyes of the
rabbits. Aqueous and vitreous samples (100 microl) were obtained half an hour
after the last drop. Instillation was continued for 7 h more and samples were
obtained as before. Drug concentrations were measured using HPLC. RESULTS: The
mean aqueous humor levels of ciprofloxacin were: in control eyes 1.31 +/- 0.78
microg/ml after 7 h and 1.85 +/- 1.69 microg/ml after 14 h of instillation: in
inflamed eyes 2.18 +/- 1.02 microg/ml after 7 h and 2.91 +/- 2.12 microg/ml after
14 h. The mean vitreous humor levels were: in control eyes 0.65 +/- 0.44
microg/ml after 7 h and 0.72 +/- 0.8 microg/ml after 14 h of instillation; in
inflamed eyes 0.67 +/- 0.77 microg/ml after 7 h and 1.01 +/- 0.43 microg/ml after
14 h. However, the differences among the groups were not significant (P > 0.05).
CONCLUSIONS: Ciprofloxacin penetration into aqueous humor was higher in 14-h
topical application than that for 7 h. Inflammation increased the penetration of
topical ciprofloxacin into aqueous while administered for 7 h and into both
aqueous and vitreous humor while administered for 14 h. c
PMID- 11011992
TI - Synthesis and in vivo evaluation of [11C]ICI 118551 as a putative subtype
selective beta2-adrenergic radioligand.
AB - Erytro-(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[ iso-propylamino]-2
butanol (ICI 118551) a potent clinically used beta2 adrenergic antagonist, was
labelled with carbon-11 (t1/2 = 20.4 min) as a potential radioligand for the non
invasive assessment of beta2 adrenergic receptors in the lung with positron
emission tomography (PET). The radiolabelled compound was prepared by reductive N
alkylation of its des-isopropyl precursor with [2-11C]acetone. (+/-)-[11C]ICI
118551 was obtained in greater than 98% radiochemical purity in 30 min with a
radiochemical yield of 15 + 5% (non-decay corrected) and a specific radioactivity
2.5 +/- 0.5 Ci/micromol. The biological evaluation of racemic erythro (+/-)
[11C]ICI 118551 in rats and Macaca Nemestrina shows a high radioactivity uptake
in lung and heart. However, in both animal models no detectable displacement of
lung radioactivity concentration was observed after pre-treatment with
propranolol or ICI 118551, which indicates that in this organ, radioligand uptake
is mostly due to non-specific binding. The biological data suggest that erythro
(+/-)-[11C]ICI 118551 is not adequate to be further developed as a tracer for
beta2 adrenergic receptor imaging in vivo.
PMID- 11011993
TI - Gastric retention and stability of lipidized Bowman-Birk protease inhibitor in
mice.
AB - Bowman-Birk protease inhibitor (BBI) was modified with a reversible lipidizing
agent. The palmitoylated product, Pal-BBI, and BBI were iodinated and orally
administered to mice using a gavage needle. A prolonged retention of Pal-BBI was
found in the stomach. Furthermore, a significant amount of Pal-BBI was detected
as intact polypeptide in the stomach of mice fed with Pal-BBI, while only
degradation products were detected with BBI. There was also a significant
increase of radioactivity in the blood and liver in mice 1.5 h post
administration of Pal-BBI. These results indicate that lipidized polypeptide can
have a longer retention and lower digestion in the stomach. They also suggest
that the Pal-BBI may have a higher gastrointestinal absorption than the original
polypeptide.
PMID- 11011994
TI - Effects of liquid phase migration on extrusion of microcrystalline cellulose
pastes.
AB - The behaviour of water-based microcrystalline cellulose pastes undergoing ram
extrusion has been investigated. Factors affecting the redistribution of water
within the extruding paste and the upstream barrel compact, such as the initial
water content, extrusion rate and die geometry, have been considered. The rates
of dewatering for these given systems were characterised by the gradients of the
extrusion pressure-ram displacement profiles. A linear relationship between the
pressure-displacement gradient and the inverse square root of the paste velocity
was obtained for a given paste and extrusion geometry. At velocities where water
migration was significant, the extrudate was found to have a higher water content
than that of the paste in the barrel at any given time; both the extrudate and
the barrel paste decreased in water content with increasing ram displacement.
Spheronisation of extrudate samples has shown that the redistribution of liquid
during extrusion is an important factor affecting the quality of the spheres. A
paste flow model, incorporating pseudo-plastic and shear deformation terms, was
used to predict the change in extrusion pressures caused by liquid phase
migration. The model parameters were obtained as functions of water content and
gave good agreement with the experimental extrusion profiles.
PMID- 11011995
TI - Oral mucosal bioadhesive tablets of pectin and HPMC: in vitro and in vivo
evaluation.
AB - The potential of tablets containing 1:4, 1:1 and 4:1 weight ratios of pectin and
hydroxypropyl methylcellulose (HPMC) for the sustained release of diltiazem by
sublingual administration has been investigated. Measurements of maximum adhesive
force to rat peritoneal membrane indicated a satisfactory bioadhesive strength.
An in vitro sustained release of diltiazem over 5 h was achieved with bilayer
tablets composed of a drug-free ethylcellulose layer in addition to the
pectin/HPMC layer containing drug. Plasma concentration-time curves obtained
following sublingual administration to rabbits of single and bilayer tablets with
1:1 weight ratios of pectin and HPMC showed evidence of sustained release of
diltiazem. Bioavailability of diltiazem was 2.5 times that achieved by oral
administration for single layer tablets and 1.8 times for the bilayered tablets.
PMID- 11011996
TI - Hydrogen bonding in salicylsalicylic acid (salsalate) crystals.
AB - An X-ray crystallographic study of the drug salsalicylic acid (salsalate) has
been performed. Crystal formation of the drug is influenced by both inter- and
intra-molecular hydrogen bonding. In addition an OH group in salsalate can occupy
alternate ortho positions resulting in two hydrogen bonding motifs within a
single crystal.
PMID- 11011997
TI - Combined effect of oleic acid and polyethylene glycol 200 on buccal permeation of
[D-ala2, D-leu5]enkephalin from a cubic phase of glyceryl monooleate.
AB - The combined use of the lipophilic permeation enhancer, oleic acid together with
polyethylene glycol 200 (PEG 200) as a co-enhancer and incorporated into the
cubic liquid crystalline phase of glyceryl monooleate was investigated in the ex
vivo buccal permeation of [D-Ala2, D-Leu5]enkephalin (DADLE) through porcine
buccal mucosa mounted in a Franz cell. The addition of oleic acid (1%) and PEG
200 (1-10%) did not change the intact appearance of the cubic phase. PEG 200
increased the aqueous solubility of oleic acid incorporated into the cubic phase
and hence promoted the transport of oleic acid into the porcine buccal mucosa.
The solubilising effect of PEG 200 on oleic acid incorporated into the cubic
phase was dependent on the PEG 200 concentration but was non-linear. The buccal
permeation flux of DADLE significantly increased when 5% (P<0.01) or 10%
(P<0.001) of PEG 200 was co-administered with 1% oleic acid compared with the
cubic phase containing 1% oleic acid alone. The present results suggest that PEG
200 enhances the action of the lipophilic permeation enhancer oleic acid and that
the combination of oleic acid and PEG 200 as a co-enhancer can be a useful tool
to improve the membrane permeability in the buccal delivery of peptide drugs
using a cubic liquid crystalline phase of glyceryl monooleate and water.
PMID- 11011999
TI - Investigation of drug release from suspension using FTIR-ATR technique: part II.
Determination of dissolution coefficient of drugs.
AB - Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy
was applied to a release experiment in order to determine the dissolution
coefficient of drug particles in heterogeneous semisolid formulations. The drug
release experiment was carried out using ketoconazole suspended in Vaseline with
various amounts of paraffinum liquidum as donor and an artificial dodecanol
collodion (DDC) membrane as acceptor compartment. Monitoring changes in IR bands
due to ketoconazole the decrease of the drug content near the ATR crystal
ointment was followed as a function of time. A mathematical model based on Fick's
second law with a source term was used to derive the apparent dissolution
coefficient Kdis by numerical fitting the experimental data. It was found that
Kdis is dependent on the fraction of paraffinum liquidum in the suspension.
Taking into account all experimental parameters required, the transport process
was simulated and discussed in terms of drug concentration- time and drug
concentration- distance profiles. Calculating the area under the mass-time curve
it was tried to predict the 'dermal bioavailability' in the acceptor (AUCa).
PMID- 11011998
TI - Investigation of drug release from suspension using FTIR-ATR technique: part I.
Determination of effective diffusion coefficient of drugs.
AB - Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy
was used to study directly the release of drug particles (ketoconazole) in a
liquid medium (paraffinum liquidum). In the case of the release experiment, the
formulation is placed on the ATR crystal and the acceptor membrane on the top of
the ointment. The decrease of the drug content in the sediment near the interface
ATR crystal-formulation in the course of the release process was quantified by
monitoring the changes of the IR spectrum in relevant spectral ranges using
multivariate analysis. A mathematical model based on Fick's second law with
appropriate initial and boundary conditions was applied in order to determine the
diffusion coefficient of the drug in the liquid medium. Knowing this value, it is
possible to calculate the effective diffusion coefficient of the drug in
heterogeneous semisolid formulation (Vaseline) as a function of the volume
fraction of the solid phase.
PMID- 11012000
TI - Skin delivery of oestradiol from lipid vesicles: importance of liposome
structure.
AB - The aim of this study was to investigate the importance of liposome structure in
oestradiol skin delivery as a tool for understanding the delivery mechanism from
lipid vesicles. Liposomes of phosphatidylcholine (PC) (1), PC, sodium cholate;
86:14 w/w (II), PC, Span 80; 86.7:13.3 w/w (III) and PC, oleic acid: 84:16 w/w
(IV) with 1 mg/ml radiolabelled drug were prepared. Saturated radiolabelled
oestradiol solutions containing the components of I-IV were separately prepared
in 90% w/w propylene glycol in water. In addition, saturated solutions containing
cholate, Span, oleic acid and ethanol at the same concentrations used in vesicles
were formulated. Oestradiol permeation through human epidermis was studied.
Formulations I-IV increased oestradiol flux by 8.6, 17, 17 and 13-fold when used
as vesicles compared with control and by 2.9. 4.0, 4.7 and 6.9-fold when used in
solution with drug. Testing individual components in solution, relative fluxes
were 2.9, 0.87, 1.1, 2.9 and 1.1 for PC, cholate. Span, oleic acid and 7%
ethanol, respectively. Accordingly, it is important to prepare phospholipids as
vesicles for efficient oestradiol skin delivery even after inclusion of oleic
acid. Penetration enhancement is not the main mechanism for improved flux.
Liposome components in solution have additive effect with a possible synergism in
some cases.
PMID- 11012001
TI - Design and in vitro evaluation of adhesive matrix for transdermal delivery of
propranolol.
AB - Propranolol hydrochloride, a water-soluble drug, was incorporated in three
transdermal delivery systems using three polymers (hydroxypropylmethylcellulose,
polyisobutylene and Ucecryl MC808). The influence of different factors (polymeric
material, matrix thickness, drug content, thickness of the adhesive layer and
presence of a dissolution enhancer) was investigated. Microscopic observations
and DSC thermograms have permitted to demonstrate that propranolol was
essentially dissolved in the HPMC matrix and dispersed in the two other matrix
types. In vitro dissolution study was carried out according to European
Pharmacopoeia. Release from HPMC matrices without adhesive coating was fast.
Release from these matrices became more regular (reduction of the burst effect)
and slow when they are coated with a 12 microm thick Ucecryl layer. Release from
different PIB matrices was too slow to be suitable as TDDS for propranolol. The
best release modulation was obtained from Ucecryl matrices. In all matrices
types, propylene glycol accelerated propranolol release rate. The kinetic of drug
release from most matrix types was more closely described by the square-root
model (Higuchi).
PMID- 11012002
TI - T cells reactive to keratinocyte antigens are generated during induction of
contact hypersensitivity in mice. A model for autoeczematization in humans?
AB - BACKGROUND: The role of keratinocytes (KC) in contact hypersensitivity (CH) has
been examined more with respect to cytokine secretion and tolerance induction and
less as a source of antigenic proteins to which chemical haptens can conjugate.
OBJECTIVE: To determine whether KC-derived proteins can serve as antigenic
carriers for haptens such as dinitrofluorobenzene (DNFB). METHODS: We examined
the capacity of draining lymph node cells from BALB/c mice sensitized to DNFB to
proliferate in response to hapten or to hapten-conjugated protein extracts
derived from a KC line (DNP-Pam KC extract). Using limiting dilution microculture
of these lymph node cells, we established DNP-specific T cell clones as well as
DNP-Pam KC extract-reactive T cell clones. We also examined the proliferative
responses of the DNP-Pam KC extract-reactive clones and of lymph node cells from
mice sensitized to different haptens. RESULTS: Lymph node cells from DNFB
sensitized mice proliferated well to hapten or to DNP-Pam KC extract. Six la(d)
restricted, alphabeta TCR-bearing, CD4+ clones were established: 4 proliferated
specifically to soluble hapten (DNBS), whereas 2 proliferated in response to DNP
Pam KC extract. Surprisingly, the DNP-Pam KC extract-reactive clones proliferated
as well to Pam KC extract without hapten. Lymph node cells from hapten-sensitized
mice not only proliferated specifically in response to the hapten to which they
were sensitized, but also proliferated to Pam KC extract without hapten.
CONCLUSIONS: T cell clones generated during the induction of (CH) in mice include
those reactive to hapten as well as those reactive to KC antigens independent of
hapten. Analogous mechanisms in humans might account for autoreactive events such
as id reactions associated with CH and angry back syndrome during patch testing.
PMID- 11012003
TI - Incidence rates of occupational allergic contact dermatitis caused by metals.
AB - BACKGROUND: Data on the incidence rates (IR) of occupational dermatoses are
scarce. MATERIAL AND METHODS: We calculated the IR of occupational allergic
contact dermatitis (ACD) caused by chromium, nickel and cobalt by occupation,
during a 7-year period (1991-1997) from the data of the Finnish Register of
Occupational Diseases and from the statistics on the working population in
different occupations. RESULTS: A total of 2543 cases of occupational ACD were
reported during 1991-1997. Cr caused 143 (5.6%) cases of ACD, Ni 176 cases (6.9%)
and Co 41 cases (1.6%) of ACD. Women had greater number of occupational ACD from
nickel, whereas occupational ACD from chromate and cobalt was more frequent in
men. The ranking list of the IR of occupational ACD caused by Cr per 10,000
working years was (incidence rate in parenthesis) (1) tanners, fellmongers, and
pelt dressers (12.20); (2) cast concrete product workers (6.94); (3) leather
goods workers (4.71), (4) metal plating and coating workers (3.66); (5)
bricklayers (3.44); (6) reinforcement concreters (2.79); and (7) building workers
(1.32). The corresponding ranking list for Ni was (1) footwear workers (2.55);
(2) machine and metal product assemblers (2.40); (3) electrical and teletechnical
equipment assemblers (2.03); (4) precision instrument mechanics (1.73); (5)
postal officials (1.48); (6) hairdressers, beauticians, and bath attendants
(1.24); (7) industrial tailors and seamstresses (1.08); and (8) waiters in cafes
and snack bars (1.04). The corresponding ranking list for Co was (1) printers
(0.80); (2) turners, machinists, and toolmakers (0.36); and (3) machine and
engine mechanics (0.17). CONCLUSION: The Finnish Register of Occupational
Diseases forms a good basis for calculating IR. As IR illustrates the risk to
become sensitized, preventive measures should be directed at occupations with the
highest IR.
PMID- 11012004
TI - Tolerance profile of a sterile moisturizer and moisturizing cleanser in irritated
and sensitive skin.
AB - BACKGROUND: This study evaluates the tolerance of preservative free sterile
cleanser and sterile moisturizer in irritated and sensitive face skin. MATERIALS
AND METHODS: An exploratory, open-label study using the cleanser and the
moisturizer in combination was performed with 98 patients with a documented
history of allergic contact dermatitis. The 2 products could each be used once or
twice daily for 28 days. The assessment parameters at baseline and end of
treatment (day 28) included the intensity of erythema, dryness/scaling by the
investigator and subjective signs (burning, pruritus and stinging), according to
a defined 4-point scale (absent to severe). In addition, a global assessment of
the change from baseline and the overall tolerance of the products were performed
by the investigator at the end of treatment. RESULTS: Ninety-four patients were
included for the efficacy analysis and 96 patients for the safety analysis. At
baseline, a majority of patients expressed some degree of erythema (63%), and
dryness/scaling (56%). Fewer patients experienced subjective signs at baseline
(44%). At the end of treatment, the results showed a statistically significant
improvement of all the objective signs of irritated skin (P = .0001, Mac Nemar
test), as well as the subjective signs of sensitive skin (P < 0.02). This was
confirmed by the overall investigator assessment, showing an excellent or good
response in 90% of the patients. In the safety analysis, 1 patient developed
contact allergy to 1 ingredient of the test products (carbomer), and 3 patients
exacerbated their dermatitis. CONCLUSION: Taken together, these results suggest
that adequately formulated cosmetics might reduce both irritated and sensitive
skin, with clinical improvement of dryness, erythema and stinging.
PMID- 11012005
TI - Efficacy of a skin-protective foam in the treatment of chronic hand dermatitis.
AB - BACKGROUND: Irritant and/or allergic hand dermatitis in individuals who are
unable to avoid causative exposures is difficult to control. Usefulness of
protective creams has been generally unsatisfactory. OBJECTIVE: To determine if
hand dermatitis, primarily of an occupational nature, could be improved by the
use of a protective foam containing dimethicone and glycerin. METHODS: Adult male
and female subjects with chronic hand dermatitis for at least 12 months, felt to
be either allergic, irritant, or combined in nature were given the study foam for
routine application after a 2-week observation period. At 2 and 6 weeks the skin
was evaluated by the investigator and subject for parameters including redness,
scaling, fissuring, blistering, and pruritus on a numerical scale. A global
evaluation also was performed. Photographs were taken at each visit. Usage of
topical corticosteroids was recorded. No systemic therapies other than
antihistamines were allowed. RESULTS: Thirty-one subjects were enrolled in the
study and 28 completed it. The physician and subject's initial global evaluations
averaged 6.13 and 5.48, respectively (0-10 scale). The final scores were 3.68 and
4.75, respectively (P < .001 for physician rating; P = .259 for subject rating).
Topical corticosteroid usage was reduced in 16 of 30 (53.6%) subjects. Twenty-one
of 30 subjects (70.0%) had improved over the course of the study. No adverse
effects were noted. CONCLUSION: This protective foam greatly or moderately
improved chronic hand dermatitis in a sizable number of individuals with
previously uncontrolled dermatitis despite continuing in their regular
occupation.
PMID- 11012006
TI - Measurement of sensory irritation of the skin.
AB - The sensory reaction to contact with chemical irritants has not been extensively
studied. This neglect has been caused partly by a lack of understanding of the
physiological basis of subjective irritation, and partly by inadequate methods of
perceptual measurement. This article begins with a brief overview of the
neurophysiology of cutaneous chemoreception (chemesthesis), and continues with a
discussion of numerous sensory, physical, and perceptual factors that can affect
the sensitivity to irritants. Then, guidelines for conducting perceptual
measurements of subjective irritation that take these factors into account are
offered. An alternative approach to direct chemosensory measurement also is
proposed that relies on the fact that many of the cutaneous receptors that are
sensitive to chemicals also are sensitive to temperature and/or mechanical
stimulation (pain or itch). It is suggested that thermal and mechanical
sensitivity might prove useful as measures of the severity of acute sensory
irritation and as indicators of subclinical sensitization by environmental
irritants.
PMID- 11012008
TI - Pitfalls in patch testing.
AB - Patch testing is an invaluable diagnostic tool in the evaluation of allergic
contact dermatitis. While TrueTest has simplified the technique for many
practitioners, there remains potential for error. We asked 4 experts to describe
their approach to several dilemmas encountered in patch testing. Their responses
will be helpful to both the veteran and tyro.
PMID- 11012007
TI - Pruritic eruption at the site of a temporary tattoo.
PMID- 11012010
TI - Amplitude degradation of time-reversed pulses in nonlinear absorbing
thermoviscous fluids.
AB - The linear wave equation in a lossless medium is time reversible, i.e., every
solution p(x, t) has a temporal mirror solution p(x, -t). Analysis shows that
time reversal also holds for the lossless nonlinear wave equation. In both cases,
time-reversal invariance is violated when losses are present. For nonlinear
propagation loses cannot normally be ignored; they are necessary to prevent the
occurrence of multivalued waveforms. Further analysis of the nonlinear wave
equation shows that amplification of a time-reversed pulse at the array elements
also leads to a violation of time reversal even for lossless nonlinear acoustics.
Numerical simulations are used to illustrate the effect of nonlinearity on the
ability of a time-reversal system to effectively focus on a target in an
absorbing fluid medium. We consider both the amplitude and arrival time of
retrodirected pulses. The numerical results confirm that both shock generation
(with the accompanying absorption) and amplification at the array, adversely
affect the ability of a time-reversal system to form strong retrodirective sound
fields.
PMID- 11012009
TI - An old reaction in a new setting: the paraben paradox.
PMID- 11012011
TI - Experimental and theoretical waveforms of Rayleigh waves generated by a
thermoelastic laser line source.
AB - An analytical model has been developed for the generation of surface acoustic
(Rayleigh) waves in an isotropic solid by a thermoelastic laser line source. For
a Gaussian light intensity profile, this model leads to an expression in closed
form for the normal surface displacement of the Rayleigh wave either in the near
field or in the far field domain. Quantitative agreement has been found for
experiments carried out with an interferometric optical probe on a duraluminum
plate.
PMID- 11012012
TI - Wave propagation in 0-3/3-3 connectivity composites with complex microstructure.
AB - This work presents a study of the properties of particulate composites. The whole
range of particle volume fraction (0-1) and ideal 0-3, 3-3 and intermediate 0-3/3
3 connectivities are analysed. Two different approaches to produce a realistic
model of the complex microstructure of the composites are considered. The first
one is based on a random location of mono-dispersed particles in the matrix;
while the second incorporates a size distribution of the particles based on
experimental measurements. Different particle shapes are also considered. A
commercial finite element package was used to study the propagation of acoustic
plane waves through the composite materials. Due to the complexity of the
problem, and as a first step, a two-dimensional model was adopted. The results
obtained for the velocity of sound propagation from the finite element technique
are compared with those from other theoretical approaches and with experimental
data. The study validates the use of this technique to model acoustic wave
propagation in 0-3/3-3 connectivity composites. In addition, the finite element
calculations, along with the detailed description of the microstructure of the
composite, provide valuable information about the micromechanics of the sample
and the influence of the microstructure on macroscopic properties.
PMID- 11012013
TI - Reflectometry using longitudinal, shear and Rayleigh waves.
AB - A new technique of reflectometry using longitudinal, shear and Rayleigh waves is
presented. Reflection coefficient as a function of angle incidence of an
ultrasound beam with a finite beamwidth was measured for water-aluminum, water
brass, and water-glass interfaces. The measured values have matched very
favorably with the results of numerical calculations based on the angular
spectrum of waves method. It has been shown that the speeds of longitudinal,
shear and Rayleigh waves of a solid can be determined very accurately by
measuring a spectacularly reflected signal versus angle of incidence.
PMID- 11012014
TI - Measurements of acoustic properties of aqueous dextran solutions in the VHF/UHF
range.
AB - The acoustic properties of aqueous solutions of dextran are characterized in the
frequency range of 70-400 MHz by the bio-ultrasonic spectroscopy system using an
ultrasonic transmission comparison method. The attenuation, velocity, impedance,
and density of aqueous dextran solutions, for six molecular weights in the range
of 10,400-2,000,000 Da in the concentration range 520% by weight, are reported.
All four parameters increase with increasing concentration. As the molecular
weight increases, the attenuation coefficient increases and the velocity
decreases. The precise frequency and molecular weight dependences of the acoustic
properties of the solutions are readily determined by the system.
PMID- 11012015
TI - Measuring Newtonian viscosity from the phase of reflected ultrasonic shear wave.
AB - In this paper, an acoustic shear impedance model is employed to obtain a relation
between the viscosity of a Newtonian fluid and phase characteristics of
ultrasonic shear wave reflection from a solid-fluid interface. The phase and
magnitude of the reflection coefficient can be decoupled in this model. The
decoupling allows an independent relation between the acoustic shear impedance
(viscosity-density product) and phase of the reflection coefficient. The model
was experimentally verified for different fluid-solid combinations. Comparison of
the results with the commonly used absolute reflection coefficient method
demonstrates that phase measurement provides improved measurements.
PMID- 11012016
TI - Experimental measurement of the acousto-electric interaction signal in saline
solution.
AB - Acoustic pressure alters local electrical conductivity in tissues and solutions.
This work concerns the measurement of electrical conductivity in a liquid which
is subjected to an acoustic pressure field created by a focused transducer.
Measurements were made with four electrodes positioned in the ultrasonic focal
zone, and the signal concerned is referred to as the acousto-electric interaction
signal. A solution of sodium chloride in a measurement cell was subjected to
ultrasound pressures of upto 1 MPa. It was shown that it is possible to
quantitate the acousto-electric interaction signal once the ultrasonic vibration
potential due to the Debye effect has been subtracted. The acousto-electric
interaction signal was shown to be directly proportional to both the applied
acoustic pressure and current. For the measurement cell used in this work, the
interaction factor was found to be 5.3 microVmA(-1) MPa(-1).
PMID- 11012017
TI - A novel approach to the aperture windowing in medical imaging.
AB - A new technique is proposed to improve the lateral resolution in the conventional
B-mode imaging systems, which enables a simple array aperture windowing in the
transmitting mode. Amplitude shaping is performed without modifying the
transmitting voltage of the array elements, but only varying the excitation pulse
length from one element to another. This method presents some attractive
practical advantages, and the reduction of the sidelobe energy is comparable to
that attainable with a conventional aperture windowing. Parametric plots are
given, which transform an amplitude apodization into a 'time apodization' for any
type of transducer array.
PMID- 11012018
TI - Computer-aided design, synthesis and biological assay of p-methylsulfonamido
phenylethylamine analogues.
AB - Class III antiarrhythmic agents selectively delay the effective refractory period
(ERP) and increase the transmembrance action potential duration (APD). Based on
our previous studies, a set of 17 methylsulfonamido phenylethylamine analogues
were investigated by 3D-QSAR techniques of CoMFA and CoMSIA. The 3D-QSAR models
proved a good predictive ability, and could describe the steric, electrostatic
and hydrophobic requirements for recognition forces of the receptor site.
According to the clues provided by this 3D-QSAR analysis, we designed and
synthesized a series of new analogues of methanesulfonamido phenylethylamine (VIa
i). Pharmacological assay indicated that the effective concentrations of delaying
the functional refractory period (FRP) 10ms of these new compounds have a good
correlation with the 3D-QSAR predicted values. It is remarkable that the maximal
percent change of delaying FRP in microM of compound VIc is much higher than that
of dofetilide. The results showed that the 3D-QSAR models are reliable.
PMID- 11012019
TI - Oxygenated chalcones and bischalcones as potential antimalarial agents.
AB - Oxygenated chalcones (3a,b) and bischalcones (4a-j) have been synthesized and
evaluated for antimalarial activity against chloroquine sensitive and resistant
strains of Plasmodium berghei in mice. Some of the screened compounds, 3a, 4c,
4e, 4f and 4i, have shown significant activity at 100 mg/kg dose against
sensitive strain.
PMID- 11012020
TI - Carbohydrate-modulated DNA photocleavage: design, synthesis, and evaluation of
novel glycosyl anthraquinones.
AB - Novel and artificial anthraquinone-carbohydrate hybrids were designed and
synthesized, and found to effectively cleave DNA under irradiation with a long
wavelength UV light and also exhibit cytotoxicity against HeLa S3 cells.
PMID- 11012022
TI - Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and
selective inhibitors of lck II.
AB - Pyrrolo[2,3-d]pyrimidines containing a 5-(4-phenoxyphenyl) substituent are novel,
potent and selective inhibitors of lck in vitro. Exploration of C-6 position of
the pyrrolo[2,3-d]pyrimidine and the terminal phenyl group structure-activity
relationship (SAR) is detailed. Compound 1 is orally active in animal models.
PMID- 11012021
TI - Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and
selective inhibitors of lck I.
AB - Pyrrolo[2,3-d]pyrimidines containing a 5-(4-phenoxyphenyl) substituent are potent
and selective inhibitors of Ick in vitro; some compounds are selective for lck
over src. Data are shown for two compounds demonstrating that they are potent and
selective inhibitors of IL2 production in cells.
PMID- 11012023
TI - Novel antifungals based on 4-substituted imidazole: a combinatorial chemistry
approach to lead discovery and optimization.
AB - A series of 4-substituted imidazole sulfonamides has been prepared by solid-phase
chemistry. These compounds were found to have good in vitro antifungal activity
and constitute the first examples of C-linked azoles with such activity. The most
potent inhibitor (30) demonstrated inhibition of key Candida strains at an in
vitro concentration of < 100nM and compared favorably with in vitro potency of
itraconazole.
PMID- 11012024
TI - The synthesis and SAR of rhodanines as novel class C beta-lactamase inhibitors.
AB - Beta-lactam antibiotics such as the cephalosporins and penicillins have
diminished clinical effectiveness due to the hydrolytic activity of diverse beta
lactamases, especially those in molecular classes A and C. A structure activity
relationship (SAR) study of a high-throughput screening lead resulted in the
discovery of a potent and selective non-beta-lactam inhibitor of class C beta
lactamases.
PMID- 11012025
TI - Expeditious synthesis and cytotoxic activity of new cyanoindolo[3,2-c]quinolines
and benzimidazo[1,2-c]quinazolines.
AB - Novel 6-cyanoindolo[3,2-c]quinoline and 6-cyanobenzimidazo[1,2-c]quinazoline
derivatives have been synthesised by treatment of the appropriate aromatic amines
with 4.5-dichloro-1,2,3-dithiazolium chloride 1 (Appel salt). The cytotoxicity
and the effect of these compounds on cellular growth were measured.
PMID- 11012026
TI - Synthesis and biological evaluation of novel piperidine carboxamide derived
calpain inhibitors.
AB - Calpain inhibitors which are derived from piperidine carboxamides in the P2
region were prepared and evaluated for mu-calpain inhibition. In particular, the
keto amides 11f and 11j have Ki of 30 and 9 nM and display a more than 100-fold
selectivity over the closely related cysteine protease cathepsin B. Furthermore,
these compounds inhibit NMDA induced convulsions in mice indicating that calpain
inhibition in brain results in some anticonvulsive properties.
PMID- 11012027
TI - Synthesis and antiproliferative activity of some benzimidazole-4,7-dione
derivatives.
AB - A series of benzimidazole-4,7-diones bearing at the 2-position the thiomethyl
group or the 2-pyridyl moiety has been synthesized and tested in vitro on three
tumor cell lines. Two of them show a very good antiproliferative effect.
Compounds 1 and 2d are more active or equiactive, respectively, than MMC against
human lymphoblastic leukemia. Both compounds exhibit high activity on human non
Hodgkin lymphoma. Compound 1 is non toxic at all the concentrations used in the
antiproliferative assay and 2d is toxic only at high concentration.
PMID- 11012028
TI - Second generation mimics of ganglioside GM1 as artificial receptors for cholera
toxin: replacement of the sialic acid moiety.
AB - In a program directed towards the design and synthesis of mimics of ganglioside
GM1, the NeuAc recognition domain was replaced by simple hydroxy acids, and the
affinity of the new ligands to the cholera toxin was determined by fluorescence
spectroscopy. The (R)-lactic acid derivative 4 was found to display the highest
affinity of the series (KD = 190 microM).
PMID- 11012029
TI - Interaction of cyanine dyes with nucleic acids. Part 19: new method for the
covalent labeling of oligonucleotides with pyrylium cyanine dyes.
AB - New chemistry for the fluorescent labeling of oligonucleotides with cyanine dyes
is proposed. It is based on the use of pyrylium salts as amine-specific reagents.
Monomethyne pyrylium cyanine dye 1 was covalently linked to 5'-aminoalkyl
modified oligonucleotide, with simultaneous conversion of the non-fluorescent dye
1 into fluorescent pyridinium cyanine structure 2.
PMID- 11012030
TI - Enhanced pneumocystis carinii activity of new primaquine analogues.
AB - New analogues of the venerable antimalarial drug primaquine have been synthesized
and bioassayed in vivo against Pneumocystis carinii, a life-threatening infection
common among immunosuppressed patients. Two of these new compounds are
significantly more active than primaquine itself, and provide new information for
future drug design and development in this area.
PMID- 11012031
TI - Diphenylsulfone muscarinic antagonists: piperidine derivatives with high M2
selectivity and improved potency.
AB - Piperidine analogues of our previously described piperazine muscarinic
antagonists are described. Piperidine analogues show a distinct structure
activity relationship (SAR) that differs from comparable piperazines. Compounds
with high selectivity and improved potency for the M2 receptor have been
identified. The lead compound, 12b, increases acetylcholine release in vivo.
Compounds of this class may be useful for the treatment of cognitive disorders
such as Alzheimer's disease (AD).
PMID- 11012032
TI - Biologically active oligodeoxyribonucleotides. Part 12: N2-methylation of 2'
deoxyguanosines enhances stability of parallel G-quadruplex and anti-HIV-1
activity.
AB - 2'-Deoxyguanosine residues of a 3',5'-end-modified hexadeoxyribonucleotide (R
95288) with anti-HIV-1 activity were substituted with N2-methyl-2'-deoxyguanosine
(m2dG). These modified oligodeoxyribonucleotides (ODNs) showed a 2-fold higher
activity than R-95288. Also, the CD spectra of these ODNs indicated that the m2dG
modification stabilized the tertiary structure of the G-quadruplex.
PMID- 11012033
TI - Development of plasmin and plasma kallikrein selective inhibitors and their
effect on M1 (melanoma) and HT29 cell lines.
AB - trans-4-Aminomethylcyclohexanecarbonyl-Tyr(O-Pic)-octylamide (YO-2) inhibited
plasmin (PL) selectively, while trans-4-aminomethylcyclohexanecarbonyl-Phe-4
carboxymethylanili de (YO-1) inhibited plasma kallikrein (PK). YO-2 induced
apoptosis of M1 (melanoma) cell line and HT29 colon carcinoma cells during 24 h
through activation of caspase-3, while YO-1 did not affect either cell line even
during 48 h.
PMID- 11012034
TI - Synthesis and antiviral activities of N-9-oxypurine 1,3-dioxolane and 1,3
oxathiolane nucleosides.
AB - Two series of 1,3-dioxolanes and 1,3-oxathiolane nucleosides containing N-9
oxypurine were synthesized as potential antiviral agents. These compounds were
prepared by reacting the sugar moieties with iodo- or bromotrimethylsilane,
followed by treatment with a mixture of sodium hydride and the desired N-hydroxy
purine base. The preparation of these N-hydroxybases was also described. No
significant antiviral activity was observed against HIV, HBV, HSV-1, HSV-2, or
HCMV.
PMID- 11012035
TI - Construction of two-stranded alpha-helix peptides based on influenza virus M1
protein selectively bound to RNA.
AB - Various 2alpha-helix peptides were designed and synthesized based on the RNA
binding region of matrix protein M1 in influenza virus. The binding properties of
the peptides to model ssRNA, ssDNA, dsDNA, and virus RNA were examined by the
fluorescence studies of a dansyl group incorporated into the peptides. The
peptide containing the hydrophilic residues of M1 RNA-binding region bound RNAs
selectively.
PMID- 11012036
TI - Synthesis and antiproliferative evaluation of 7-aminosubstituted
pyrroloiminoquinone derivatives.
AB - Coupling of five amines on the 7-methoxy-1,3,4,5-tetrahydropyrrolo[4,3,2
de]quinoline core was achieved and afforded, in particular, an opened analogue of
the natural alkaloid wakayin. Evaluation of cytotoxic activity of compounds 2, 10
13 on L1210 cells afforded IC50 in the range 0.25 5.3 microM.
PMID- 11012038
TI - Ain't no rhythm fast enough: EEG bands beyond beta.
PMID- 11012037
TI - The synthesis and biological evaluation of a novel series of phthalazine PDE4
inhibitors I.
AB - This communication describes the synthesis and in vitro evaluation of a novel and
potent series of phosphodiesterase type IV (PDE4) inhibitors. The compounds
described represent conformationally constrained analogues of RP 73401,
Piclamilast. Preliminary evidences of reduced side effects of II compared to
standards are also reported.
PMID- 11012039
TI - High-frequency oscillations (20 to 120 Hz) and their role in visual processing.
AB - Oscillatory firing of neurons in response to visual stimuli has been observed to
occur with different frequencies at multiple levels of the visual system. In the
cat retina, oscillatory firing patterns occur with frequencies in the range of 60
to 120 Hz (omega-oscillations). These millisecond-precise temporal patterns are
transmitted reliably to the cortex and may provide a feed-forward mechanism of
response synchronization. In the cortex, visual responses often show oscillatory
patterning with frequencies between 20 and 60 Hz (gamma-oscillations), which are
not phase locked to the stimulus onset and therefore do not show up in regularly
averaged evoked potentials. Gamma-oscillatory responses synchronize with
millisecond precision over long distances and are mediated by the reciprocal
corticocortical connectivity. Modulatory systems like the ascending reticular
activating system facilitate synchronization and increase the strength of gamma
oscillations. During states of such functional cortical activation, the dominant
frequency of the EEG is shifted from lower frequencies in the delta-/theta-range
to higher frequencies in the gamma-range. Therefore, functional states indicate
different degrees of temporal precision with which large neuronal populations
interact. Response synchronization also depends on relations of global stimulus
features. This suggests that millisecond-precise neuronal interactions serve as a
fundamental mechanism for visual information processing.
PMID- 11012040
TI - Ripple (approximately 200-Hz) oscillations in temporal structures.
AB - Spontaneous network oscillations near 200 Hz have been described in the
hippocampus and parahippocampal regions of rodents and humans. During the last
decade the characteristics and the mechanisms behind these field "ripples" have
been studied extensively, mainly in rodents. They occur during rest or slow-wave
sleep and provide a very fast, short-lasting (approximately 50 msec) rhythmic and
synchronous activation of specific projection cells and interneurons. Ripples are
frequently triggered by a massive synaptic activation from the hippocampal CA3
subfield, which is called a sharp wave. Recent evidence suggests that ripples
have a specific task in memory processing-namely, that they convey information
stored in the hippocampus to the cortex where it can be preserved permanently.
Network mechanisms involved in ripple oscillations may be relevant for
understanding pathologic synchronization processes in temporal lobe epilepsy.
PMID- 11012041
TI - Linking 600-Hz "spikelike" EEG/MEG wavelets ("sigma-bursts") to cellular
substrates: concepts and caveats.
AB - Somatosensory evoked human EEG and magnetoencephalographic (MEG) responses
comprise a brief burst of low-amplitude, high-frequency (approximately 600 Hz)
spikelike wavelets ("sigma-bursts") superimposed on the primary cortical response
(e.g., the N20 to electrical median nerve stimulation). The recent surge of
interest in these macroscopic sigma-burst responses is energized by the prospect
of monitoring noninvasively, highly synchronized and rapidly repeating population
spikes generated in the human thalamic and cortical somatosensory system. Thus,
analyses of spike-related sigma-bursts could uniquely complement conventional low
frequency EEG/MEG, reflecting mass excitatory and inhibitory postsynaptic
potentials that potentially also incorporate subthreshold activities of
undetermined functional relevance. Recent studies using spatiotemporal source
analysis of multichannel recordings identified regional burst sources
subcortically (near-thalamic) as well as cortically. At the primary somatosensory
cortex, sigma-burst generators showed the well-established homuncular somatotopic
ordering. Functionally, the 600-Hz burst appears to comprise multiple
subcomponents with differential sensitivity to stimulus rate, intensity, sleep
wake cycle, tactile interference, subject age, and certain movement disorders. A
plenitude of cellular candidates contributing to burst generation at different
levels can already now be envisaged, including cuneothalamic and thalamocortical
relay cells, as well as cortical bursting pyramidal cells and fast-spiking
inhibitory interneurons. Although cellular burst coding might serve to relay
information with high efficiency, concepts to link macroscopic sigma-bursts and
cellular substrates call for additional study.
PMID- 11012042
TI - I-waves in motor cortex.
AB - I-waves refer to high-frequency (approximately 600 Hz) repetitive discharge of
corticospinal fibers produced by single-pulse stimulation of the motor cortex.
First detected in animal preparations, this multiple discharge can also be
recorded in humans with epidural electrodes over the spinal cord, and with
recently developed noninvasive paired-pulse transcranial magnetic stimulation
protocols. The exact nature of the generation of I-waves is still unclear, but
there is convincing evidence that they originate in the motor cortex, mainly
through activation of corticocortical projections onto corticospinal neurons. The
ability to measure I-waves in human motor cortex allows one to test the integrity
and excitability of the underlying corticocortical circuits in health and
disease.
PMID- 11012043
TI - Train duration effects on perception: sensory deficit, neglect, and cerebral
lateralization.
AB - The mechanisms of conscious perception are uncertain. In a preliminary study,
dramatic effects of train duration on perception in a patient with right brain
stroke were noted. In this study, the mechanisms of train duration on perception
of peripheral somatosensory stimuli are examined. Subjects included healthy
adults and patients with right brain infarctions. Train duration effects on
perception were examined in relation to cerebral infarction, handedness, age,
elevated peripheral threshold via bupivacaine, and impaired attention via
diazepam or scopolamine. Perceptual thresholds to electrical pulses on the hand
decreased as train duration increased, but only over the first several hundred
milliseconds. Compared to controls, right brain stroke patients showed much
greater lowering of threshold in the affected hand as train duration was
extended. Age and bupivacaine elevated thresholds, but had little or no influence
on train duration effects. Diazepam and scopolamine had no effect on thresholds.
Thresholds were lower in the left than right hand of healthy dextral subjects,
irrespective of age. Sinistral subjects had less left/right asymmetry. Increased
train duration effect in patients is not explained by a primary elevation in
threshold or by impaired vigilance. Lower perceptual thresholds in the left hand
of healthy dextral subjects is consistent with right cerebral dominance for
externally directed attention.
PMID- 11012044
TI - EEG telemetry with closely spaced electrodes in frontal lobe epilepsy.
AB - The use of additional electrodes (other than standard 10-20 electrodes) has
proved to be extremely useful in the investigation of patients with temporal lobe
epilepsy. The development of 32- and 64-channel EEG machines, along with the
reformatting capabilities of digital EEG has greatly increased the possibilities
in the number of electrodes and recording montages. The authors wanted to
determine whether the use of closely spaced electrodes designed to increase the
coverage of frontocentral regions is of benefit in the investigation of patients
with frontocentral epilepsy. Patients investigated for frontocentral epilepsy
underwent EEG telemetry with closely spaced electrodes based on the 10-10
nomenclature. Twenty-three patients were studied. An additional 30 minutes was
required by technicians to create the montage. Unilateral frontal or
frontocentral epileptic abnormalities were observed in 10 patients, independent
bifrontal in 5 patients, synchronous bifrontal in 4 patients, and no EEG changes
in 4 patients. In no patient did the addition of closely spaced electrodes lead
to a change in the classification of the EEG. Closely spaced electrodes did not
reveal focal abnormalities, which were not already apparent with 10-20
electrodes, nor did they demonstrate evidence of laterality in bilaterally
synchronous discharges.
PMID- 11012045
TI - Abnormal vasoreaction to arousal stimuli--an early sign of diabetic sympathetic
neuropathy demonstrated by laser Doppler flowmetry.
AB - Early diagnosis of diabetic autonomic neuropathy contributes to the prevention of
serious complications and improves the prognosis of patients with diabetes.
Common tests of peripheral autonomic function are the quantitative sudomotor axon
reflex test or the sympathetic skin response (SSR). Quantitative sudomotor axon
reflex test is quantifiable but technically demanding. Sympathetic skin response
cannot be quantified easily. To study whether measurement of skin vasomotion is
suited to assess early sympathetic peripheral neuropathy, we monitored skin blood
flow at the index finger pulp using laser Doppler flowmetry before and after
electrical stimulation. We assured that the stimulus was sufficient to elicit an
efferent sympathetic response by monitoring palmar SSR ipsilateral to the flow
measurement. In 21 diabetic patients with at least stage one polyneuropathy and
21 age-matched controls, SSR was recorded from one palm and sole following
electrical stimulation at the contralateral wrist. Sympathetic skin response was
present at the palms in all patients and controls and absent at the sole of two
patients only. Eight patients (38.9%) had abnormal SSR, with absent plantar
responses in two patients, prolonged plantar latencies in six patients, and
prolonged volar SSR latencies in two patients. Skin blood flow responses were
more often abnormal (46.1%) than SSR (P < 0.05), responses were delayed in two
patients and absent in another 8 patients. Skin blood flow retest reliability was
high with a repeatability coefficient of 10.64% in controls and 12.34 % in
patients. Skin blood flow monitoring after sympathetic stimulation provides a
reproducible parameter of sympathetic vasomotor control and complements the
diagnostic value of SSR testing.
PMID- 11012046
TI - Maximal and minimal motor conduction velocity in amyotrophic lateral sclerosis
and X-linked bulbospinal muscular atrophy measured by Harayama's collision
method.
AB - Measurement of the maximal (Vmax) and minimal (Vmin) motor nerve conduction
velocities was performed in amyotrophic lateral sclerosis (ALS), bulbospinal
muscular atrophy (BSMA), and control subjects. The collision method as described
initially by Harayama and coworkers was used. This allowed for the correction of
the velocity recovery effect (VRE) in Hopf's original method. The purpose of this
study is to clarify the controversial results regarding the Vmin and the
difference between Vmax and Vmin (Vmax-Vmin) in ALS and to compare these results
with BSMA, and clarify the usefulness of Harayama's method. In ALS, a reduction
of Vmax and Vmin, and an increase of Vmax-Vmin were found in both median and
posterior tibial nerve. In BSMA, a reduction of Vmin and an increase of Vmax-Vmin
in the median nerve were noted. Some patients whose results of conventional nerve
conduction study were entirely within normal range showed abnormal results in
Vmin and/or Vmax-Vmin. These results suggest that the correction of VRE is
essential to determine a Vmin, and motor fibers with abnormally slow conduction
velocities were present in ALS and BSMA. Harayama's collision method is useful to
detect abnormalities of motor fibers with submaximal conduction velocities.
PMID- 11012047
TI - Radical excision of intramedullary spinal cord tumors: surgical morbidity and
long-term follow-up evaluation in 164 children and young adults.
AB - OBJECT: The majority of intramedullary spinal cord tumors (IMSCT) in children and
young adults are low-grade gliomas. Radical resection of similar tumors in the
cerebral hemisphere or cerebellum is usually curative; however, the conventional
management for IMSCTs remains partial resection followed by radiotherapy because
of the concern for surgical morbidity. Nevertheless, radical resection of IMSCTs
without routine adjuvant treatment has been the rule at our institution since
1980. In an attempt to resolve this controversy, the long-term morbidity and
survival in a large series of children have been retrospectively reviewed.
METHODS: The database records and current status of 164 patients 21 years of age
and younger in whom an IMSCT was resected were reviewed. A gross-total resection
(>95%) was achieved in 76.8% of the surgical procedures. Subtotal resections (80
95%) were performed in 20. 1%. The majority of patients (79.3%) had
histologically low-grade lesions. There were no deaths due to surgery. When
comparing the preoperative and 3-month postoperative functional grades, 60.4%
stayed the same, 15.8% improved, and 23.8% deteriorated. Only 13 patients
deteriorated by more than one functional grade. Patients with either no deficits
or only mild deficits before surgery were rarely injured by the procedure,
reinforcing the importance of early diagnosis and treatment. The major
determinant of long-term patient survival was histological composition of the
tumor. The 5-year progression-free survival rate was 78% for patients with low
grade gliomas and 30% for those with high-grade gliomas. Patients in whom an
IMSCT was only partially resected (<80%) fared significantly worse. CONCLUSIONS:
The long-term survival and quality of life for patients with low-grade gliomas
treated by radical resection alone is comparable or superior to minimal resection
and radiotherapy. The optimum therapy for patients with high-grade gliomas is yet
to be determined.
PMID- 11012048
TI - Nonsurgically managed patients with degenerative spondylolisthesis: a 10- to 18
year follow-up study.
AB - OBJECT: Controversy exists concerning the indications for surgery and choice of
surgical procedure for patients with degenerative spondylolisthesis. The goals of
this study were to determine the clinical course of nonsurgically managed
patients with degenerative spondylolisthesis as well as the indications for
surgery. METHODS: A total of 145 nonsurgically managed patients with degenerative
spondylolisthesis were examined annually for a minimum of 10 years follow-up
evaluation. Radiographic changes, changes in clinical symptoms, and functional
prognosis were surveyed. Progressive spondylolisthesis was observed in 49
patients (34%). There was no correlation between changes in clinical symptoms and
progression of spondylolisthesis. The intervertebral spaces of the slipped
segments were decreased significantly in size during follow-up examination in
patients in whom no progression was found. Low-back pain improved following a
decrease in the total intervertebral space size. A total of 84 (76%) of 110
patients who had no neurological deficits at initial examination remained without
neurological deficit after 10 years of follow up. Twenty-nine (83%) of the 35
patients who had neurological symptoms, such as intermittent claudication or
vesicorectal disorder, at initial examination and refused surgery experienced
neurological deterioration. The final prognosis for these patients was very poor.
CONCLUSIONS: Low-back pain was improved by restabilization. Conservative
treatment is useful for patients who have low-back pain with or without pain in
the lower extremities. Surgical intervention is indicated for patients with
neurological symptoms including intermittent claudication or vesicorectal
disorder, provided that a good functional outcome can be achieved.
PMID- 11012049
TI - Incidence and outcome of kyphotic deformity following laminectomy for cervical
spondylotic myelopathy.
AB - OBJECT: The authors undertook a study to explore the predisposing risk factors,
frequency of occurrence, and clinical implications of kyphosis following
laminectomy for cervical spondylotic myelopathy (CSM). METHODS: Preoperative
radiological studies were available in 46 patients with CSM who had undergone
laminectomy. Records were reviewed to obtain demographic data and operative
reports. Preoperative radiographs were assessed to determine spinal alignment. In
a follow-up interview the authors established clinical outcome and patient
satisfaction. Postoperative cervical alignment and mobility was also determined
by assessing lateral neutral, flexion, and extension x-ray films. Preoperatively,
the cervical spine was shown to be kyphotic in four (9%) of 46, straight in 20
(43%) of 46, and lordotic in 22 (48%) of 46 patients. Nine (21%) of 42 patients
with either straight or lordotic alignment demonstrated in the preoperative
period developed kyphosis after surgery. Kyphosis developed in six (30%) of 20
patients in whom straight spinal alignment was demonstrated preoperatively and in
only three (14%) of 22 patients in whom lordosis was found preoperatively.
Clinically, 13 (29%) of 45 patients improved and 19 (42%) of 45 remained
unchanged after an average 4-year follow-up period; 36 (80%) patients believed
that their surgery was successful (one patient, who was mentally retarded, could
not respond to the follow-up questionnaire). Spinal alignment was not predictive
of outcome; cervical mobility as demonstrated on flexion and extension, however,
correlated with improved functional performance (p = 0.005). CONCLUSIONS:
Kyphosis may develop in up to 21% of patients who have undergone laminectomy for
CSM. Progression of the deformity appears to be more than twice as likely if
preoperative radiological studies demonstrate a straight spine. In this study,
clinical outcome did not correlate with either pre- or postoperative sagittal
alignment.
PMID- 11012050
TI - Treatment of Down syndrome-associated craniovertebral junction abnormalities.
AB - OBJECT: Operative intervention for craniovertebral junction (CVJ) instability in
patients with Down syndrome has become controversial, with reports of a low
incidence of associated neurological dysfunction and high surgical morbidity
rates. The authors analyzed their experience in light of these poor results and
attempted to evaluate differences in management. METHODS: Medical and
radiographic records of 36 consecutive patients with Down syndrome and CVJ
abnormalities were reviewed. The most common clinical complaints included neck
pain (15 patients) and torticollis (12 patients). Cervicomedullary compression
was associated with ataxia and progressive weakness. Hyperreflexia was documented
in a majority of patients (24 cases), and 13 patients suffered from varying
degrees of quadriparesis. Upper respiratory tract infection precipitated the
presentation in five patients. Four patients suffered acute neurological insults
after a minor fall and two after receiving a general anesthetic agent.
Atlantoaxial instability was the most common radiographically observed
abnormality (23 patients), with a rotary component present in 14 patients.
Occipitoatlantal instability was also frequently observed (16 patients) and was
coexistent with atlantoaxial dislocation in 15 patients. Twenty individuals had
bone anomalies, the most frequent of which was os odontoideum (12 patients)
followed by atlantal arch hypoplasia and bifid anterior or posterior arches
(eight patients). Twenty-seven patients underwent surgical procedures without
subsequent neurological deterioration, and a 96% fusion rate was observed. In
five of 11 patients basilar invagination was irreducible and required transoral
decompression. Overall, 24 patients enjoyed good or excellent outcomes.
CONCLUSIONS: The results of this series highlight the clinicopathological
characteristics of CVJ instability in patients with Down syndrome and suggest
that satisfactory outcomes can be achieved with low surgical morbidity rates.
PMID- 11012051
TI - Single-stage anterior-posterior decompression and stabilization for complex
cervical spine disorders.
AB - OBJECT: To evaluate the applicability and safety of single-stage combined
anterior-posterior decompression and fusion for complex cervical spine disorders,
the authors retrospectively reviewed 72 consecutive procedures of this type
performed using a uniform technique at a single center. METHODS: The indications
for decompression and stabilization included: postlaminectomy kyphosis (15
patients), trauma (19 patients), spondylosis and congenital stenosis (32
patients), and ossification of the posterior longitudinal ligament (six
patients). All patients underwent anterior cervical corpectomies in which
allograft fibula and plates were placed, with 89% of patients undergoing two- or
three-level procedures (range one-four levels). Lateral mass plating with
autograft (morselized iliac crest) fusion was performed in all patients while the
same anesthetic agent was still in effect. A hard cervical collar was used
postoperatively in all patients (mean 13 weeks). All patients were followed for a
minimum of 2 years (mean 29 months). Fusion was determined to be successful in
all 72 patients (100%). Although the short-term morbidity rate reached 32%, the
significant long-term morbidity rate was only 5%. At the 2-year follow-up
examination, anterior cervical plate dislodgment was seen in one patient, and 16
of the 516 lateral mass screws implanted were observed to have partially backed
out. However, there were no cases of nerve root injury, strut graft extrusion, or
anterior plate or screw fracture. There were no clinically significant hardware
complications and no patient required repeated operation. CONCLUSIONS: The
combined single-stage anterior-posterior decompression, reconstruction, and
instrumentation procedure represents a viable option in the treatment of a select
group of patients with complex cervical spinal disorders. The technique provides
immediate rigid stabilization of the cervical spine, prevents anterior plate
failure or strut graft extrusion, and eliminates the need for halo immobilization
postoperatively. Furthermore, a higher rate of fusion is achieved with this
combined approach than with the anterior approach alone.
PMID- 11012052
TI - A randomized prospective study of an anterior cervical interbody fusion device
with a minimum of 2 years of follow-up results.
AB - OBJECT: Despite variations in technique, inherent problems persist with current
approaches to anterior cervical fusion. This study was performed to determine
whether anterior cervical fusion performed using an investigational device was
safe and effective in the treatment of degenerative cervical disc disorders and
whether this device offered advantages over current techniques. METHODS: Fifty
four patients with radiculopathy with or without mild myelopathy due to one- or
two-level cervical degenerative disc disease were randomized as part of a Food
and Drug Administration device study. Following microsurgical discectomy, the
control group was treated with iliac crest graft fusion; the experimental study
group underwent insertion of an interspace cage and placement of a local
autograft. All patients received postoperative follow-up care for at least 2
years. Good or excellent results were found in approximately 97% of the
experimental group and 88% of the control group. A solid fusion was achieved in
all patients who underwent one-level cage placement, and a solid fusion at one or
both levels was achieved in over 90% of both groups. Chronic donor site pain was
reported by 31% of the control group. CONCLUSIONS: In this study, the use of an
interbody fusion cage avoided donor site morbidity and placement of autograft
achieved a high rate of good or excellent results. Interbody fusion cages appear
safe and effective, and their use helps to avoid some of the inherent problems in
performing current anterior cervical fusion techniques.
PMID- 11012053
TI - Direct anterior screw fixation for recent and remote odontoid fractures.
AB - OBJECT: The management of odontoid fractures remains controversial. Only direct
anterior screw fixation provides immediate stabilization of the spine and may
preserve normal C1-2 motion. To determine the indications, optimum timing, and
results for direct anterior screw fixation of odontoid fractures, the authors
reviewed the surgery-related outcome of patients who underwent this procedure at
two institutions. METHODS: One hundred forty-seven consecutive patients (98 males
and 49 females) who underwent direct anterior screw fixation for recent (< or = 6
months postinjury [129 patients]) or remote (> or = 18 months postinjury [18
patients]) Type II (138 cases) or III (nine cases) odontoid fractures at the
University of Utah (94 patients) and National Institute of Traumatology in
Budapest, Hungary (53 patients) between 1986 and 1998 are included in this study
(mean follow up 18.2 months). Data obtained from clinical examination, review of
hospital charts, operative findings, and imaging studies were used to analyze the
surgery-related results in these patients. In patients with recent fractures
there was an overall bone fusion rate of 88%. The rate of anatomical bone fusion
of recent fractures was significantly (p < or = 0.05) higher in fractures
oriented in the horizontal and posterior oblique direction (compared with
anterior oblique), but this finding was independent (p > or = 0.05) of age, sex,
number of screws placed (one or two), and the degree or the direction of odontoid
displacement. In patients with remote fractures there was a significantly lower
rate of bone fusion (25%). Overall, complications related to hardware failure
occurred in 14 patients (10%) and those unrelated to hardware in three patients
(2%). There was one death (1%) related to surgery. CONCLUSIONS: Direct anterior
screw fixation is an effective and safe method for treating recent odontoid
fractures (<6 months postinjury). It confers immediate stability, preserves C1-2
rotatory motion, and achieves a fusion rate that compares favorably with
alternative treatment methods. In contradistinction, in patients with remote
fractures (> or = 18 months postinjury) a significantly lower rate of fusion is
found when using this technique, and these patients are believed to be poor
candidates for this procedure.
PMID- 11012054
TI - Spinal nerve root repair and reimplantation of avulsed ventral roots into the
spinal cord after brachial plexus injury.
AB - OBJECT: The authors review the first series of 10 cases in which injured
intraspinal brachial plexus were surgically repaired. They describe the technique
of spinal cord implantation or repair of ruptured nerve roots, as well as patient
outcome. METHODS: Spinal root repair/implantation was performed from 10 days to 9
months postinjury. There were nine male patients and one female patient.
Postoperatively in most cases, regeneration of motor neurons from the spinal cord
to denervated muscles could be demonstrated. The first signs of regeneration were
noted approximately 9 to 12 months postoperatively. Useful function with muscle
power of at least Medical Research Council Grade 3 occurred in three of 10 cases.
Magnetic brain stimulation studies revealed a normal amplitude and latency from
the cortex to reinnervated muscles on surgically treated and control sides. A
certain degree of cocontraction between antagonistic muscles (for example, biceps
triceps) compromised function. With time there was a reduction of cocontractions,
probably due to spinal cord plasticity. In these cases there was also,
surprisingly, a return of sensory function, although the mechanism by which this
occurred is uncertain. Sensory stimulation (thermal and mechanical) within the
avulsed dermatomes was perceived abnormally and/or experienced at remote sites.
There was some return of patients' sense of joint position. CONCLUSIONS: A short
time lag between the accident and the surgery was recognized as a significant
factor for a successful outcome. Reimplantation of avulsed nerve roots may be
combined with other procedures such as nerve transfers in severe cases of
brachial plexus injury.
PMID- 11012055
TI - Anatomical projection of the cervical uncinate process in ventral, ventrolateral,
and posterior decompressive surgery.
AB - OBJECT: The cervical uncinate processes (UPs), their variations, and the
relationships between the neurovascular structures and surrounding bone were
investigated in this anatomical study. The object of this study was to highlight
the important surgery-related considerations associated with ventral,
ventrolateral, and posterior decompressive surgery. METHODS: Forty-nine adult C3
7 dry bone samples were used, and 10 measurements were obtained for each
vertebra. The anterior measurements involved the cervical uncinate process (UP):
height, width, length, distance between its tip and vertebral foramina,
interuncinate process distance, sagittal angle with the superior margin of the
vertebral body (VB), VB anteroposterior diameter, and VB width. Posterior
measurements involved the vertical distance between the superior border of the
lamina at the lamina-facet joint and the tip of the UP, as well as the horizontal
distance between the medial-most border of the superior facet and the tip of the
UP. All symmetrical structures were measured bilaterally. There were no
statistically significant differences between right- and left-sided measurements
in this series. The height of the UP increased gradually at each segmental level
between C-3 and C-7. The width of the UP did not change with segmental level (5.0
mm at C-3 compared with 5.3 mm at C-7). On average, the length of the UP was
relatively constant. The distance from the tip of the UP to vertebral foramina
averaged 1 mm at the C2-3 level and 1.5 mm at the C5-6 level. Interuncinate
distance and VB width gradually increased and were highly variable, which
appeared to be related with osteophyte formation. There was a slight gradual
increase from C-3 to lower segments, and it paralleled with the midline
anteroposterior diameter of the same VB. The angle between the UP and the
superior margin of the VB exhibited great variety. The posterior measurements
decreased gradually from C-3 to C-7. CONCLUSIONS: Based on the data obtained in
this study, a surgeon is provided with a three-dimensional orientation as well as
anatomical knowledge. This knowledge also allows for a more effective
neurovascular decompression by minimizing the surgery-related complications.
PMID- 11012056
TI - In vitro biomechanical analysis of three anterior thoracolumbar implants.
AB - OBJECT: The goal of this study was to evaluate the comparative efficacy of three
commonly used anterior thoracolumbar implants: the anterior thoracolumbar locking
plate (ATLP), the smooth-rod Kaneda (SRK), and the Z-plate. METHODS: In vitro
testing was performed using the T9-L3 segments of human cadaver spines. An L-1
corpectomy was performed, and stabilization was achieved using one of three
anterior devices: the ATLP in nine spines, the SRK in 10, and the Z-plate in 10.
Specimens were load tested with 1.5-, 3-, 4.5-, and 6-Nm in flexion and
extension, right and left lateral bending, and right and left axial rotation.
Angular motion was monitored using two video cameras that tracked light-emitting
diodes attached to the vertebral bodies. Testing was performed in the intact
state in spines stabilized with one of the three aforementioned devices after the
devices had been fatigued to 5000 cycles at +/- 3 Nm and after bilateral
facetectomy. There was no difference in the stability of the intact spines with
use of the three devices. There were no differences between the SRK- and Z-plate
instrumented spines in any state. In extension testing, the mean angular rotation
(+/- standard deviation) of spines instrumented with the SRK (4.7 +/- 3.2
degrees) and Z-plate devices (3.3 +/- 2.3 degrees) was more rigid than that
observed in the ATLP-stabilized spines (9 +/- 4.8 degrees). In flexion testing
after induction of fatigue, however, only the SRK (4.2 +/- 3.2 degrees) was
stiffer than the ATLP (8.9 +/- 4.9 degrees). Also, in extension postfatigue, only
the SRK (2.4 +/- 3.4 degrees) provided more rigid fixation than the ATLP (6.4 +/-
2.9 degrees). All three devices were equally unstable after bilateral
facetectomy. The SRK and Z-plate anterior thoracolumbar implants were both more
rigid than the ATLP, and of the former two the SRK was stiffer. CONCLUSIONS: The
authors' results suggest that in cases in which profile and ease of application
are not of paramount importance, the SRK has an advantage over the other two
tested implants in achieving rigid fixation immediately postoperatively.
PMID- 11012057
TI - In vitro biomechanical investigation of the stability and stress-shielding effect
of lumbar interbody fusion devices.
AB - OBJECT: Interbody fusion devices are rapidly gaining acceptance as a method of
ensuring lumbar interbody arthrodesis. Although different types of devices have
been developed, the comparative reconstruction stability remains controversial.
It also remains unclear how different stress-shielded environments are created
within the devices. Using a calf spine model, this study was designed to compare
the construct stiffness afforded by 11 differently designed lumbar interbody
fusion devices and to quantify their stress-shielding effects by measuring
pressure within the devices. METHODS: Sixty-six lumbar specimens obtained from
calves were subjected to anterior interbody reconstruction at L4-5 by using one
of the following interbody fusion devices: four different threaded fusion cages
(BAK device, BAK Proximity, Ray TFC, and Danek TIBFD), five different nonthreaded
fusion devices (oval and circular Harms cages, Brantigan PLIF and ALIF cages, and
InFix device); two different types of allograft (femoral ring and bone dowel)
were used. Construct stiffness was evaluated in axial compression, torsion,
flexion, and lateral bending. Prior to testing, a silicon elastomer was injected
into the cages and intracage pressures were measured using pressure needle
transducers. CONCLUSIONS: No statistical differences were observed in construct
stiffness among the threaded cages and nonthreaded devices in most of the testing
modalities. Threaded fusion cages demonstrated significantly lower intracage
pressures compared with nonthreaded cages and structural allografts. Compared
with nonthreaded cages and structural allografts, threaded fusion cages afforded
equivalent reconstruction stiffness but provided more stress-shielded environment
within the devices.
PMID- 11012058
TI - Lasting paraplegia caused by loss of lumbar spinal cord interneurons in rats: no
direct correlation with motor neuron loss.
AB - OBJECT: The aims of this study were to investigate further the role played by
lumbar spinal cord interneurons in the generation of locomotor activity and to
develop a model of spinal cord injury suitable for testing neuron replacement
strategies. METHODS: Adult rats received intraspinal injections of kainic acid
(KA). Locomotion was assessed weekly for 4 weeks by using the Basso, Beattie, and
Bresnahan (BBB) 21-point locomotor scale, and transcranial magnetic motor evoked
potentials (MMEPs) were recorded in gastrocnemius and quadriceps muscles at 1 and
4 weeks. No changes in transcranial MMEP latency were noted following KA
injection, indicating that the descending motor pathways responsible for these
responses, including the alpha motor neurons, were not compromised. Rats in which
KA injections included much of the L-2 segment (10 animals) showed severe
locomotor deficits, with a mean BBB score of 4.5 +/- 3.6 (+/- standard
deviation). Rats that received lesions rostral to the L-2 segment (four animals)
were able to locomote and had a mean BBB score of 14.6 +/- 2.6. Three rats that
received only one injection bilaterally centered at L-2 (three animals) had a
mean BBB score of 3.2 +/- 2. Histological examination revealed variable loss of
motor neurons limited to the injection site. There was no correlation between
motor neuron loss and BBB score. CONCLUSIONS: Interneuron loss centered on the L
2 segment induces lasting paraplegia independent of motor neuron loss and white
matter damage, supporting earlier suggestions that circuitry critical to the
generator of locomotor activity (the central pattern generator) resides in this
area. This injury model may prove ideal for studies of neuron replacement
strategies.
PMID- 11012059
TI - Effect of aluminum on neurological recovery in rats following spinal cord injury.
AB - OBJECT: This investigation was undertaken to study the effect of aluminum on
neurobehavioral, electrophysiological, structural, and biochemical changes in
rats following spinal cord injury (SCI). METHODS: Adult male Sprague-Dawley rats
classified into different groups were given aluminum sulfate-dosed drinking water
in the concentrations of 0%, 0.25%, 0.5% and 1%, respectively. After 30 days of
aluminum treatment, the animals were subjected to spinal cord trauma. Laminectomy
was performed at T7-8 in anesthetized rats, followed by placement of a
compression plate (2.2 x 5 mm) loaded with a 35-g weight over the exposed spinal
cord for 5 minutes. Control animals underwent the same surgical procedure, but
the compression injury was not induced (sham). Postoperative neurological
function was assessed using the inclined-plane test and by obtaining a modified
Tarlov score and vocal/sensory score daily for 10 days. Electrophysiological
changes were assessed using corticomotor evoked potentials, whereas pathological
changes were assessed by light microscopy. The level of vitamin E in the spinal
cord was measured as an index of antioxidant defense. The behavioral,
biochemical, and histological analyses were performed in a blinded fashion.
CONCLUSIONS: Analysis of results obtained in the behavioral studies revealed that
the compression of spinal cord produced transient paraparesis in which a maximum
motor deficit occurred at Day 1 following SCI and resolved over a period of 10
days. Administration of aluminum significantly impaired the recovery following
SCI. Analysis of the results of the biochemical, electrophysiological, and
histopathological studies also confirmed the deleterious effects of aluminum on
recovery from SCI in rats.
PMID- 11012060
TI - New approach to cervical flexion deformity in ankylosing spondylitis. Case
report.
AB - The treatment of cervical fixed flexion deformity in ankylosing spondylitis
presents a challenging problem that is traditionally managed by a corrective
cervicothoracic osteotomy. The authors report a new approach to this problem that
involves performing a two-level osteotomy at the level of maximum spinal
curvature, thereby achieving complete anatomical correction in a one-stage
procedure. This 48-year-old woman with ankylosing spondylitis presented with a 30
year history of progressive neck deformity that left her unable to see ahead and
caused her to experience difficulty eating, drinking, and breathing on exertion.
On examination, she exhibited a 90 degrees fixed flexion deformity of the
cervical spine, which was maximum at C-4; this was confirmed on imaging studies.
A two-level osteotomy was performed at C3-4 and C4-5 around the area of maximum
spinal curvature, and the deformity was corrected by extending the head on its
axis of rotation through the uncovertebral joints. The spine was stabilized using
a Ransford loop. An excellent anatomical position was achieved, as was complete
correction of the deformity. A two-level midcervical osteotomy performed at the
level of maximum spinal curvature in ankylosing spondylitis enables complete
correction of severe fixed flexion deformity in a single procedure. Preservation
of the uncovertebral joints allows smooth and safe correction of the deformity
about their axis of rotation.
PMID- 11012061
TI - Dorsal arachnoid web with spinal cord compression: variant of an arachnoid cyst?
Report of two cases.
AB - Spinal arachnoid cysts are diverticula of the subarachnoid space that may
compress the spinal cord; these lesions are most commonly found in the thoracic
spine. Two patients who presented with thoracic myelopathy were noted on magnetic
resonance imaging to have focal indentation of the dorsal thoracic cord, with
syringomyelia inferior to the site of compression. Both patients were found at
operation to have discrete arachnoid "webs" tenaciously attached to the dura
mater and pia mater. These webs were not true arachnoid cysts, yet they blocked
the flow of cerebrospinal fluid (CSF) and caused focal compression of the spinal
cord. The mass effect appeared to be the result of a pressure gradient created by
the obstruction of CSF flow in the dorsal aspect of the subarachnoid space. Both
patients responded well to resection of the arachnoid web. Arachnoid webs appear
to be rare variants of arachnoid cysts and should be suspected in patients with
focal compression of the thoracic spinal cord.
PMID- 11012062
TI - Calcifying pseudoneoplasms of the spine with myelopathy. Report of two cases.
AB - The authors describe two cases of calcifying pseudoneoplasms, rare degenerative
lesions that mimic tumor or infection. One case involved the cervical spine and
the second the thoracic spine. Both patients experienced progressive myelopathy
from extradural compression of the spinal cord. The radiological evaluation,
pathological findings in the lesions, treatment, and follow up are described.
Total or subtotal excision can relieve symptoms and prevent recurrence of this
lesion.
PMID- 11012063
TI - Subacute posttraumatic ascending myelopathy after spinal cord injury. Report of
three cases.
AB - Subacute posttraumatic ascending myelopathy is a rare disorder, unrelated to
syrinx formation or mechanical instability, that may gradually emerge within the
first 1 to 2 weeks after a spinal cord injury. The authors describe three
patients with this syndrome and discuss its possible causes as well as its
clinical presentation, imaging characteristics, treatment, and patient prognosis.
PMID- 11012064
TI - Rotational compression of the vertebral artery at the point of dural penetration.
Case report.
AB - Vertebrobasilar insufficiency (VBI) due to vertebral artery (VA) compression
occurs in a significant number of patients. Rotational compression of the VA
usually occurs below C-2, where the artery is pinched during head rotation,
leading to thrombus formation and subsequent cerebellar infarction. Although this
problem has been reported to occur at the atlantooccipital levels, a review of
the literature revealed no published cases of VA compression at the point of
dural penetration, which is located above the atlantooccipital membrane. The
authors report the case of a 30-year-old woman who presented with signs and
symptoms of VBI. Dynamic angiography demonstrated left-sided VA compression at
the site at which dural penetration had occurred, proximal to the posterior
inferior cerebellar artery. Surgical decompression of the left VA at the point of
dural penetration relieved the symptoms, and postoperative dynamic angiography
demonstrated complete resolution of the positional compression of the left VA.
Because of these findings, an additional possible location for rotational
compression of the VA is described, namely, the point of dural penetration. The
authors suggest a method of surgically treating rotational VA compression at this
site.
PMID- 11012065
TI - Embolization of spinal cord arteriovenous malformations with an ethylene vinyl
alcohol copolymer dissolved in dimethyl sulfoxide (Onyx liquid embolic system).
Report of two cases.
AB - In this paper the authors describe the first use of a new liquid embolic agent
(Onyx) to treat spinal cord arteriovenous malformations (AVMs). Because its
properties make it more predictable to use than currently available liquid
agents, the authors believe that this material has great potential in the
endovascular management of both spinal cord and brain AVMs. This very promising
agent merits further clinical study.
PMID- 11012066
TI - Split cord malformation with partial eventration of the diaphragm. Case report.
AB - The authors describe the case of a 3-year-old girl who presented with a dorsal
split cord malformation (SCM) and was found to have eventration of the diaphragm.
Although the child did not undergo surgery for eventration, its presence suggests
a need for careful preoperative planning and clinical evaluation to rule out or
confirm the anomalies associated with spinal dysraphism or SCM.
PMID- 11012067
TI - Eosinophilic granuloma of the spine: early spontaneous disappearance of tumor
detected on magnetic resonance imaging. Case report.
AB - Two cases of eosinophilic granuloma (EG) of the spine associated with
neurological deficits are presented. The patients were treated conservatively by
using external fixation with a brace as well as bed rest. Neurological deficits
and pain diminished and finally disappeared as the tumor mass decreased in size,
as seen on magnetic resonance (MR) imaging. During the 5-year follow-up period no
recurrence of the tumors was detected on MR images. Surgical treatment for spinal
EG in children presenting with typical vertebra plana is not recommended except
for those with severe or progressive palsy and for those in whom the disease
requires differential diagnosis.
PMID- 11012068
TI - Intraspinal familial clear cell meningioma in a mother and child. Case report.
AB - The authors present a case of familial clear cell meningioma in which the proband
is a child with an intraspinal tumor. The clear cell meningioma variant has
recently been studied. The literature regarding clear cell meningioma is
reviewed.
PMID- 11012069
TI - Intraspinal extradural myxopapillary ependymoma of the sacrum arising from the
filum terminale externa. Case report.
AB - Extradural ependymomas of the sacrococcygeal region are very rare, with most
arising from the soft tissues of the presacral area or from the regions dorsal to
the sacrum. In even rarer circumstances, the tumor may arise within the sacral
canal, likely as a result of ependymal cells of the extradural filum terminale.
Because of bone erosion caused by extension of the tumor into the pelvis or
dorsal to the sacrum, a truly intraspinal extradural ependymoma in this region
has until now never been clearly demonstrated. The authors present a patient with
a myxopapillary ependymoma arising from the filum terminale externa in which
there was no involvement of the intradural filum or extension outside the sacral
canal. A review of the literature is presented, with emphasis on the pathogenesis
and clinical management of these rare tumors.
PMID- 11012070
TI - Traumatic intratumoral hemorrhage as the presenting symptom of a spinal
neurinoma. Case report.
AB - Intratumoral hemorrhage as the presenting symptom of spinal tumors is rare. The
authors describe a patient who presented with rapidly progressing paraplegia 24
hours after sustaining a minor traumatic injury of the thoracic spine.
Radiological evaluation demonstrated a low-thoracic intradural tumor that was
resected and found to be a neurinoma in which severe intra- and peritumoral
hemorrhage was revealed. The radiological, surgical, and pathological findings
are presented and discussed.
PMID- 11012071
TI - A rare complication of hardware failure in neurostimulation. Report of two cases.
AB - The authors report on a rare complication of neurostimulation. Two patients
presented with a skin rash after undergoing neurostimulator implantation, and the
implants were found to have faulty electrical insulation. The rash was centered
over the source of current leak and disappeared when the problem was corrected.
PMID- 11012072
TI - The "open book" technique for preparation of the lumbar transverse process for
posterolateral fusion.
AB - A new technique is reported for preparation of the recipient graft bed for
posterolateral intertransverse process fusion of the lumbar spine. The dorsal
surface of each transverse process is reflected open like the pages of a book.
This increases the surface area of cancellous bone in the recipient bed, thereby
promoting better contact with the grafted bone. This maneuver also preserves much
of the periosteal blood supply to the dorsal aspect of the transverse process and
much of the cortical bone that would normally be drilled away during
decortication. The technical details are described.
PMID- 11012073
TI - Vertebral erosion and a ligamentum flavum cyst. Case illustration.
PMID- 11012074
TI - Spinal nerve root repair after brachial plexus injury.
PMID- 11012075
TI - Interbody cages.
PMID- 11012076
TI - The use of methylprednisolone.
PMID- 11012077
TI - Diffuse idiopathic skeletal hyperostosis.
PMID- 11012078
TI - Endoscopic sympathectomy.
PMID- 11012079
TI - DNases and apoptosis.
AB - Here we review the different apoptotic DNases. From a functional point of view,
DNases implicated in apoptosis may be classified into three groups: the Ca2+/Mg2+
endonucleases, the Mg2+-endonucleases, and the cation-independent endonucleases.
The first group includes DNase I which has no specificity for the linker region,
DNase gamma which has some homology with DNase I, and other DNases which cleave
DNA in the linker region. Both DNase I and DNase gamma have been cloned. The
other nucleases of this category have dispersed molecular weights. Their
sequences are unknown and it is difficult to determine their role(s) in
apoptosis. It seems that different pathways are present and that these nucleases
may be activated either by caspases or serine proteases. The caspase 3 activated
DNase (CAD, CPAN, or DFF40) belongs to the Mg2+-dependent endonucleases. DNase II
belongs to the third group of acid endonucleases or cation-independent DNases. We
have shown the involvement of DNase II in lens cell differentiation. Recently,
the molecular structure of two different enzymes has been elucidated, one of
which has a signal peptide and appears to be secreted. The other, called L-DNase
II, is an intracellular protein having two enzymatic activities; in its native
form, it is an anti-protease, and after posttranslational modification, it
becomes a nuclease.
PMID- 11012080
TI - Molecular correlates of the action of bis(ethyl)polyamines in breast cancer cell
growth inhibition and apoptosis.
AB - Polyamines are known to be involved in cell growth regulation in breast cancer.
To evaluate the efficacy of bis(ethyl)polyamine analogs for breast cancer therapy
and to understand their mechanism of action we measured the effects of a series
of polyamine analogs on cell growth, activities of enzymes involved in polyamine
metabolism, intracellular polyamine levels, and the uptake of putrescine and
spermidine using MCF-7 breast cancer cells. The IC50 values for cell growth
inhibition of three of the compounds, N1,N12-bis(ethyl)spermine, N1,N11
bis(ethyl)norspermine, and N1,N14-bis(ethyl)homospermine, were in the range of 1
2 microM. Another group of three compounds showed antiproliferative activity at
about 5 microM level. These compounds are also capable of suppressing colony
formation in soft agar assay and inducing apoptosis of MCF-7 cells. The highly
effective growth inhibitory agents altered the activity of polyamine biosynthetic
and catabolic enzymes and down-regulated the transport of natural polyamines,
although each compound produced a unique pattern of alterations in these
parameters. HPLC analysis showed that cellular uptake of bis(ethyl)polyamines was
highest for bis(ethyl)spermine. We also analyzed polyamine analog conformations
and their binding to DNA minor or major grooves by molecular modelling and
molecular dynamics simulations. Results of these analyses indicate that tetramine
analogs fit well in the minor groove of DNA whereas, larger compounds extend out
of the minor groove. Although major groove binding was also possible for the
short tetramine analogs, this interaction led to a predominantly bent
conformation. Our studies show growth inhibitory activities of several
potentially important analogs on breast cancer cells and indicate that multiple
sites are involved in the mechanism of action of these analogs. While the
activity of an analog may depend on the sum of these different effects, molecular
modelling studies indicate a correlation between antiproliferative activity and
stable interactions of the analogs with major or minor grooves of DNA.
PMID- 11012082
TI - Disruption of LT-antigen/p53 complex by heat treatment correlates with inhibition
of DNA synthesis during transforming infection with SV40.
AB - Transforming infection of Go/G1-arrested primary mouse kidney cell cultures with
simian virus 40 (SV40) induces cells to re-enter the S-phase of the cell cycle.
In Go-arrested cells, no p53 is detected, whereas in cells induced to proliferate
by infection, a gradual accumulation of p53 complexed to SV40 large T-antigen is
observed in the nucleus. Heat treatment of actively proliferating SV40-infected
cells leads to inhibition of DNA synthesis and growth arrest. To determine the
fate of p53 after heat treatment, proliferating infected cells were exposed to
mild heat (42.5 degrees C) for increasing lengths of time. The results presented
here show that after ninety minutes of treatment, the arrest of DNA synthesis by
heat correlates with the disruption of the p53/LT-antigen complex. Longer
treatments induce, in addition, a reduction in the solubility of p53, which was
recovered tightly associated with the nuclear fraction. This contrasted with
large T-antigen, whose solubility remained unaffected by heat treatment. Although
the total amount of p53 in the nucleus remained constant, as shown by immunoblot
analyses, p53 was no longer detectable after immunoprecipitation or by
immunofluorescent staining techniques. These results suggest that heat treatment
had either induced conformational changes in its antigenic sites, or had
sequestered the sites through aggregation or binding to insoluble nuclear
components.
PMID- 11012081
TI - Stress-relaxation and contraction of a collagen matrix induces expression of TGF
beta and triggers apoptosis in dermal fibroblasts.
AB - Extracellular matrix serves as a scaffold for cells and can also regulate gene
expression and ultimately cell behaviour. In this study, we compared the effects
of three forms of type I collagen matrix, which differed only in their mechanical
properties, and plastic on the expression of transforming growth factor-beta1
(TGF-beta1), matrix metalloproteinase-1 (collagenase), and type I collagen and on
the growth and survival of human dermal fibroblasts. These effects were
correlated with alterations in cell morphology and organization of intracellular
actin. Cells in detached or stress-relaxed matrices were spherical, lacked stress
fibres, and showed increased TGF-beta1 mRNA compared to the cells in anchored
collagen matrices or on plastic, which were polygonal or bipolar and formed
stress fibres. The levels of TGF-beta measured by bioassay were higher in
detached and stress-relaxed collagen matrices, than in anchored collagen
matrices. Cells on plastic contained little or no immunoreactive TGF-beta, while
most cells in collagen matrices were stained. The levels of collagenase mRNA were
significantly higher in all the collagen matrix cultures compared to those on
plastic, but there were no statistically significant differences between them.
Levels of mRNA for procollagen type I were not significantly affected by culture
in the collagen matrices. Apoptotic fibroblasts were detected by the TUNEL assay
in detached (5.7%) and to a lesser extent in stress-relaxed (2.2%) matrices, but
none were observed in anchored collagen matrices or on plastic. These results
show that alterations in the mechanical properties of matrix can induce the
expression of TGF-beta and trigger apoptosis in dermal fibroblasts. They further
suggest that inability to reorganize this matrix could be responsible for the
maintenance of the fibroproliferative phenotype associated with fibroblasts in
hypertrophic scarring.
PMID- 11012083
TI - Effect of pineal indoles on activities of the antioxidant defense enzymes
superoxide dismutase, catalase, and glutathione reductase, and levels of reduced
and oxidized glutathione in rat tissues.
AB - Male Sprague-Dawley rats were randomly divided into four groups. Two of the
groups received a single intraperitoneal injection of melatonin and 5
methoxytryptamine (5 mg/kg body weight), respectively, at 9 PM. One group
received an intraperitoneal injection of 5-methoxytryptophol (5 mg/kg body
weight) at 9 AM. The remaining group received alcoholic saline (vehicle) and
served as the control. All rats were sacrificed 90 min after injection and the
livers, kidneys, and brains were dissected. The activities of superoxide
dismutase, catalase, and glutathione reductase in the organs were measured. It
was found that both melatonin and 5-methoxytryptamine were approximately
equipotent in enhancing the activities of superoxide dismutase and glutathione
reductase in the kidney and liver, while 5-methoxytryptophol displayed a weaker
effect. Both melatonin and 5-methoxytryptamine augmented the level of reduced
glutathione in the kidney and liver, while 5-methoxytryptophol did so only in the
kidney. All three pineal indoles increased the activity of superoxide dismutase
and lowered the ratio of oxidized to reduced glutathione in the brain.
PMID- 11012084
TI - Identification and characterization of gelatin-cleavage activities in the
apically located extracellular matrix of the sea urchin embryo.
AB - We have identified and partially characterized several gelatinase activities
associated with the sea urchin extraembryonic matrix, the hyaline layer. A
previously identified 41-kDa collagenase/gelatinase activity was generally not
found to be associated with isolated hyaline layers but was dissociated from the
surface of 1-h-old embryos in the absence of Ca2+ and Mg2+. While hyaline layers,
freshly prepared from 1-h-old embryos, were devoid of any associated gelatinase
activities, upon storage at 4 degrees C for 4 days, a number of gelatin-cleavage
activities appeared. Comparative analysis of these activities with the 41-kDa
collagenase/gelatinase revealed that all species were inhibited by
ethylenediamine tetraacetic acid but were refractory to inhibition with the
serine protease inhibitors, phenylmethyl sulfonyl fluoride and benzamidine. In
contrast, the largely Zn2+ specific chelator 1,10-phenanthroline had markedly
different effects on the gelatinase activities. While several of the storage
induced, hyaline-layer-associated gelatinase activities were inhibited, the 41
kDa collagenase/gelatinase was refractory to inhibition as was a second
gelatinase species with an apparent molecular mass of 45 kDa. We also examined
the effects of a series of divalent metal ions on the gelatin-cleavage
activities. In both qualitative and quantitative assays, Ca2+ was the most
effective activator while Mn2+, Cu2+, Cd2+, and Zn2+ were all inhibitory. In
contrast, Mg2+ had a minimal inhibitory effect on storage-induced gelatinase
activities but significantly inhibited the 41-kDa collagenase/gelatinase. These
results identify several distinct gelatin-cleavage activities associated with the
sea urchin extraembryonic hyaline layer and point to diversity in the biochemical
nature of these species.
PMID- 11012085
TI - Lectins from bulbs of the Chinese daffodil Narcissus tazetta (family
Amaryllidaceae).
AB - The isolation of three lectins with similar N-terminal amino acid sequences from
the bulbs of the Chinese daffodil Narcissus tazetta was achieved. The isolation
protocol involved ion exchange chromatography on DEAE-cellulose, affinity
chromatography on mannose-agarose, and fast protein liquid chromatography-gel
filtration on Superose 12. The lectins were all adsorbed on mannose-agarose and
demonstrated a single band with a molecular weight of 13 kDa in SDS
polyacrylamide gel electrophoresis and a single 26 kDa peak in gel filtration,
indicating that they were mannose-binding, dimeric proteins. The lectins differed
in hemagglutinating activity, with the magnitude of the activity correlating with
the ionic strength of the buffer required to elute the lectin from the DEAE
cellulose column. The bulb lectin did not exert potent cytotoxicity against
cancer cell lines or fetal bovine lung cells but inhibited syncytium formation
in, and reinstated viability of, fetal bovine lung cells infected with bovine
immunodeficiency virus.
PMID- 11012086
TI - Divergent responses of ras-transfected and non-ras-transfected human
keratinocytes to extracellular calcium.
AB - Raising extracellular calcium (Ca(o)) induces terminal differentiation in
cultured epidermal keratinocytes. The introduction of the ras oncogene into
keratinocytes results in resistance to Ca(o)-mediated differentiation. To
understand the signaling mechanism involved, we examined the Ca(o)-induced
formation of inositol triphosphate (IP3) and changes in intracellular Ca2+
(Ca(i)) concentration in non-ras-transfected and ras-transfected HaCaT lines of
human keratinocytes. When switched from 0.05- to 1.5-mM Ca(o) medium, the non-ras
HaCaT line showed a rapid twofold increase in IP3 formation, whereas the IP3
level in the ras-transfected I-7 line was slightly affected. G-protein-coupled
activation of phospholipase was intact in both lines, as evidenced by the
generation of similar amounts of IP3 in response to addition of bradykinin or
guanosine 5'-[gamma-thio]-triphosphate. Addition of 1.0 mM Ca(o) evoked similar
Ca(i) responses in both non-ras- and ras-transfected cells: a transient
elevation, followed by a sustained lower plateau. However, the two lines differed
in their later responses: after being maintained in 1.0 mM Ca2+ for 24 h, the
Ca(i) level was significantly lower in ras-transfected cells than in non-ras
transfected HaCaT cells. The Ca(o)-induced increase in Ca(i) in both lines was
inhibited by the Ca2+ entry blocker SK&F 96365 or depolarization in high K+
bathing solution, demonstrating its dependence of calcium influx. The results
suggest fundamental differences in the early signal that are generated in
response to an increase in Ca(o) in ras-transfected keratinocytes, with the
absence of a Ca(o)-induced rise in IP3--a signaling pathway defect that may play
a role in the differentiation block the cells exhibit. In addition, the inability
of ras-transfected cells to sustain a prolonged Ca(i) plateau may also contribute
to their inability to differentiate in response to the Ca(o) signal.
PMID- 11012087
TI - The ZF87/MAZ transcription factor functions as a growth suppressor in
fibroblasts.
AB - ZF87/MAZ is a zinc finger transcription factor that activates expression of
tissue-specific genes and represses expression of the c-myc proto-oncogene.
Infection of NIH3T3 fibroblasts with a retrovirus expressing ZF87/MAZ leads to a
significant reduction in G418-resistant colonies, compared to cells infected with
a retroviral control. Further, only a small fraction of the G418-resistant
colonies express ZF87/MAZ. When the ZF87/MAZ-expressing colonies are expanded,
they demonstrate a slow growth phenotype, a delayed transit through G1 phase and
a decrease in endogenous c-myc gene expression and cyclin A and cyclin E protein
levels. Consistent with a partial G1 arrest, the ZF87/MAZ-expressing cells show a
reduced sensitivity to the S phase specific chemotherapeutic agent camptothecin.
These data indicate that ZF87/MAZ is a growth suppressor protein in
nontransformed cells, in part, by affecting the levels of key cell cycle
regulatory proteins.
PMID- 11012088
TI - Reversible changes in size of cell nuclei isolated from Amoeba proteus: role of
the cytoskeleton.
AB - Micrurgically isolated interphasal nuclei of Amoeba proteus, which preserve F
actin cytoskeletal shells on their surface, shrink after perfusion with imidazole
buffer without ATP, and expand to about 200% of their cross-sectional area upon
addition of pyrophosphate. These changes in size may be reproduced several times
with the same nucleus. The shrunken nuclei are insensitive to the osmotic effects
of sugars and distilled water, whereas the expanded ones react only to the
distilled water, showing further swelling. The shrinking-expansion cycles are
partially inhibited by cytochalasins. They are attributed to the state of
actomyosin complex in the perinuclear cytoskeleton, which is supposed to be in
the rigor state in the imidazole buffer without ATP, and to dissociate in the
presence of pyrophosphate. Inflow of external medium to the nuclei during
dissociation of the myosin from the perinuclear F-actin may be due to colloidal
osmosis depending on other macromolecular components of the karyoplasm.
PMID- 11012089
TI - Kidney proximal tubule cells: epithelial cells without EGTA-extractable annexins?
AB - The expression and the subcellular localizations of annexins I, II, IV, VI, and
XIII in renal epithelial cells were investigated, using immunological techniques
with specific monoclonal antibodies. Upon performing Western blotting
experiments, no annexins VI and XIII were detected in kidney, whereas annexins I,
II, and IV were. Immunofluorescence labelling procedure performed on thin frozen
renal sections showed the presence of these three annexins along the plasma
membrane of the collecting duct cells with a restricted expression of annexin I
at principal cells. Annexin I was also found present in some glomerular cells.
None of these annexins, however, were detected in the proximal tubular cells upon
performing immunofluorescence labelling and electrophoretic analysis on an EGTA
(ethylenebis(oxyethylenenitrilo)tetraacetic acid)-extractable annexin fraction
prepared from freshly isolated cells. This is the first time a mammalian
epithelial cell has been found to express non-typical annexin (at least partly
solubilized with EGTA). However, when these cells were grown in primary culture,
they were found to express annexins I, II, IV, and V. As well as being located
along the basolateral membrane, annexins I and II are also present on vesicles,
which suggests that these annexins may be involved in vesicular traffic under
cell culture conditions.
PMID- 11012090
TI - Contractile elements of Lemna trisulca L. glycerinated cell models during
chloroplast translocations.
AB - Electron microscopy of Lemna glycerinated cell models depicts contractile
elements during chloroplast translocations. One contractile element, the thin
ectoplasmic layer, is < or = 0.4 microm thick, pressed against plasma membrane
cell wall. Thin ectoplasmic layer contains numerous oriented filaments and some
appear to be actin and myosin. Another contractile element is the outer
chloroplast membrane which envelops each chloroplast and joins or fuses with the
thin ectoplasmic layer. Chloroplast interconnections are formed between two or
more chloroplasts by outer chloroplast membranes; they enhance chloroplast
communications, translocations, and molecular exchanges.
PMID- 11012091
TI - Expression of heat shock protein 47(Hsp47) mRNA levels in rabbit connective
tissues during the response to injury and in pregnancy.
AB - Hsp47 (also termed "colligin") is a 47 kDa protein that is localized in the ER
and cis-Golgi vesicles of fibrocytes, chondrocytes, and other collagen-secreting
cells. Under stress conditions, Hsp47 expression is upregulated as part of the
heat shock/stress response that mitigates cell damage from noxious stimuli such
as elevated temperature, heavy metals, and oxidative stress. Under non-stress
conditions, Hsp47 functions as a collagen-specific molecular chaperone that
facilitates intracellular procollagen polypeptide synthesis, and triple helix
assembly in connective tissues. Previously it has been shown that levels of
collagen-specific gene expression are significantly altered in ligaments,
menisci, and other connective tissues of the rabbit following surgically induced
injuries (increased), and during pregnancy (decreased). The present study was
undertaken to determine whether expression of mRNA for the Hsp47 collagen-binding
stress protein was also influenced in these experimental models. Since no
sequence information was available on the rabbit Hsp47 gene, a partial cDNA for
rabbit Hsp47 was first isolated and cloned using reverse transcriptase PCR (RT
PCR) with degenerate oligonucleotide primers. Rabbit Hsp47 sequence-specific
primers then designed enabled analysis of Hsp47 mRNA expression in rabbit
connective tissues using semiquantitative RT-PCR. It was found that Hsp47
expression is affected in a complex, tissue-specific manner by injury and
pregnancy. Hsp47 transcript levels were elevated in the medial collateral
ligament (MCL) of the rabbit knee following surgical induction of a gap injury.
Transection of the anterior cruciate ligament (ACL), which leads to chronic
progressive damage to menisci of the rabbit knee joint, was accompanied by an
upregulation of Hsp47 expression in the medial and lateral menisci. Hsp47 mRNA
levels were depressed during pregnancy in the kidney and ACL of primigravid
adolescent rabbits, but were not altered in corneal tissue during pregnancy or in
the ACL of skeletally mature multiparous females. The changes in Hsp47 transcript
levels within these connective tissues following injury/pregnancy often, but not
always, paralleled changes in collagen-specific gene expression.
PMID- 11012092
TI - Characterization of the interaction of recombinant apolipoprotein(a) with
modified fibrinogen surfaces and fibrin clots.
AB - Elevated levels of lipoprotein(a) [Lp(a)] in plasma are a significant risk factor
for the development of atherosclerotic disease, a property which may arise from
the ability of this lipoprotein to inhibit fibrinolysis. In the present study we
have quantitated the binding of recombinant forms of apolipoprotein(a) [17K and
12K r-apo(a); containing 8 and 3 copies, respectively, of the major repeat
kringle sequence (kringle IV type 2)] to modified fibrinogen surfaces. Iodinated
17K and 12K r-apo(a) bound to immobilized thrombin-modified fibrinogen (i.e.,
fibrin) surfaces with similar affinities (Kd approximately 1.2-1.6 microM). The
total concentration of binding sites (Bmax) present on the fibrin surface was
approximately 4-fold greater for the 12K than for the 17K (Bmax values of 0.81 +/
0.09 nM, and 0.20 +/- 0.01 nM respectively), suggesting that the total binding
capacity on fibrin surfaces is reduced for larger apolipoprotein(a) (apo(a))
species. Interestingly, binding of apo(a) to intact fibrin was not detected as
assessed by measurement of intrinsic fluorescence of free apo(a) present in the
supernatants of sedimented fibrin clots. In other experiments, the total
concentration apo(a) binding sites available on plasmin-modified fibrinogen
surfaces was shown to be 13.5-fold higher than the number of sites available on
unmodified fibrin surfaces (Bmax values of 2.7 +/- 0.3 nM and 0.20 +/- 0.01 nM
respectively) while the affinity of apo(a) for these surfaces was similar. The
increase in Bmax was correlated with plasmin-mediated exposure of C-terminal
lysines since treatment of plasmin-modified fibrinogen surfaces with
carboxypeptidase B produced a significant decrease in total binding signal as
detected by ELISA (enzyme linked immunosorbent assay). Taken together, these data
suggest that apo(a) binds to fibrin with poor affinity (low microM) and that the
total concentration of apo(a) binding sites available on modified-fibrinogen
surfaces is affected by both apo(a) isoform size and by the increased
availability of C-terminal lysines on plasmin-degraded fibrinogen surfaces.
However, the low affinity of apo(a) for fibrin indicates that Lp(a) may inhibit
fibrinolysis through a mechanism distinct from binding to fibrin, such as binding
to plasminogen.
PMID- 11012093
TI - Transforming growth factor beta1 selectively regulates ferritin gene expression
in malignant H-ras-transformed fibrosarcoma cell lines.
AB - Transforming growth factor beta1 is an important growth regulator in many cell
types, usually exerting a negative effect on cellular growth. Inhibition of DNA
synthesis and cell proliferation is frequently lost during malignant
transformation, and in some cases, tumor cell proliferation is actually
stimulated by TGF-beta1. The present study demonstrates a novel link between
alterations in TGF-beta1 regulation during malignant conversion, and the
expression of ferritin, an important activity involved in a number of biological
functions including iron homeostasis and cell-growth control. A series of H-ras
transformed mouse 10 T 1/2 cell lines, exhibiting increasing malignant potential,
was investigated for possible TGF-beta1-mediated changes in ferritin gene
expression. Selective induction of gene expression was observed, since only H-ras
transformed cells with malignant potential exhibited marked elevations in
ferritin gene expression, in particular, alterations in H-ferritin gene
expression. The regulation of H-ferritin gene expression in response to TGF-beta1
did not involve alterations in transcription, but occurred through mechanisms of
post-transcriptional stabilization of the H-ferritin mRNA. Additionally, evidence
was obtained for a cycloheximide-sensitive regulator of H-ferritin gene
expression, since the presence of this protein synthesis inhibitor increased H
ferritin message levels, and in combination with TGF-beta1, cooperated in an
additive manner to augment H-ferritin gene expression. These results show for the
first time that TGF-beta1 can regulate ferritin gene expression in malignant H
ras transformed cells, and suggest a mechanism for growth factor stimulation of
malignant cells, in which early alterations in the control of H-ferritin gene
expression are important.
PMID- 11012094
TI - The role of blood tumor marker measurement (using a biochemical index score and c
erbB2) in directing chemotherapy in metastatic breast cancer.
AB - The role of blood tumor markers in monitoring response in advanced breast cancer
is established in endocrine therapy and standard chemotherapy. This study
examines marker levels in patients receiving new chemotherapy regimens. Thirty
patients were recruited into two multicenter trials in which docetaxel-based
regimens were used in 15 patients. The other 15 received doxorubicin-based
regimens. Biochemical response calculated from a score using CA15.3, CEA and ESR
was compared with UICC response. Marker changes at 2, 4 and 5 months correlated
with UICC response at 3, 4(1/2) and 6 months, respectively (p < 0.03). Eleven
patients achieved both clinical/radiological and biochemical response at the end
of treatment; markers had not yet returned to below cutoffs in seven, suggesting
a possible advantage to continue chemotherapy. No patient showed a biochemical
response whilst judged clinically/radiologically progressive. Nineteen patients
had progressed either clinically/radiologically or biochemically at six months;
of these, eight showed progression assessed earlier by markers so that a median
of four cycles of chemotherapy could have been saved. Measurements of serum c
erbB2 showed a correlation with tissue c-erbB2 staining in the primary tumor (p <
0.003). Among the patients with positive tissue staining, sequential changes in
serum c-erbB2 completely paralleled initial response.
PMID- 11012095
TI - CCND1 mRNA overexpression is highly related to estrogen receptor positivity but
not to proliferative markers in primary breast cancer.
AB - To elucidate the role of CCND1 alterations in sporadic breast cancer we
investigated the possible link between CCND1 mRNA levels versus estrogen-receptor
(ER) status and a proliferation marker, S-phase fraction (SPF), measured by flow
cytometry. CCND1 expression was quantified by means of real-time quantitative RT
PCR in a well-characterized series of 33 primary breast cancer patients. Eighteen
tumors (54.5%) showed CCND1 overexpression ranging from 3.3 to 29.5 times the
level observed in normal breast tissue. Seventeen (94.4%) of the 18 cases with
CCND1 overexpression were ER-positive compared to seven (46.7%) of the 15 cases
with normal CCND1 expression (p=0.0074). CCND1 overexpression was independent of
SPF and DNA-ploidy status. These data suggest that the CCND1 gene does not act as
an oncogene responsible for more rapid cell proliferation in breast cancer, but
could be involved in the regulation of hormone sensitivity associated with ER.
PMID- 11012096
TI - Relationship of tumoral hyaluronic acid and cathepsin D contents with
histological type of gastric carcinoma.
AB - The aim of this work was to evaluate the cytosolic contents of hyaluronic acid
(HA) and cathepsin D (CatD) in gastric carcinomas and their possible
relationships with the clinicopathological parameters of the tumors. Our study
demonstrated a wide variability in the cytosolic levels of HA (mean +/- SEM: 3748
+/- 411 ng/mg protein) and cathepsin D (52 +/- 4 pmol/mg protein) in the tumors
of 78 gastric cancer patients. In addition, the tumoral contents of HA and CatD
were significantly higher (p<0.005) in diffuse type (HA: 6027 +/- 1099 ng/mg
protein; CatD: 75 +/- 13 pmol/mg protein) than in intestinal type (HA: 2735 +/-
242 ng/mg protein; CatD: 42 +/- 3 pmol/mg protein) carcinomas. These data suggest
that both markers may contribute to the biological characterization of gastric
carcinomas.
PMID- 11012097
TI - BTA-TRAK combined with urinary cytology is a reliable urinary indicator of
recurrent transitional cell carcinoma (TCC) of the bladder.
AB - This study evaluated the diagnostic accuracy of BTA-TRAK in combination with
urinary cytology (UC) in the follow-up of patients with a history of transitional
cell carcinoma (TCC) of the bladder. The overall sensitivity of BTA-TRAK, UC and
the two tests combined for the detection of recurrences was 82.7% (48/58), 84.2%
(48/57) and 91.2% (52/57), respectively. BTA and UC showed comparable sensitivity
for superficial recurrences (76.7% (33/43) and 78.5% (33/42), respectively) and
for invasive recurrences (100% (15/15)); when the two tests were used in
combination, the sensitivity for superficial lesions increased to 88% (37/42).
BTA-TRAK was more sensitive than UC for G1 recurrences (81.2% (13/16) vs. 68.7%
(11/16)), and when the two tests were combined the sensitivity increased to 87.5%
(14/16). The sensitivity of the combination was 100% (15/15) for G3 lesions. The
differences in urinary BTA-TRAK levels between patients with recurrences and
those without evidence of disease were statistically significant (Wilcoxon's
test, p<0.05); among patients with recurrences BTA levels were significantly
higher in the invasive and poorly differentiated subtypes. In the series of
patients studied by us, BTA-TRAK combined with UC was shown to be a non-invasive,
accurate test to predict TCC recurrences. Periodic measurement of BTA-TRAK
combined with urinary cytology seems to provide additional information for the
monitoring of patients treated for TCC; however, due to the presence of false
positive and false negative results, this test cannot replace cystoscopy. In a
selected group of patients it could, if combined with cytology and
ultrasonography and if correctly used and interpreted, orient the timing and
indication for cystoscopy.
PMID- 11012098
TI - Cholestasis is the main determinant of abnormal CA 19-9 levels in patients with
liver cirrhosis.
AB - BACKGROUND/AIMS: Altered CA19-9 levels are commonly found in patients with liver
cirrhosis though a clear explanation for this finding has not yet been given. The
aim of this study was to investigate whether CA19-9 levels might be related to
alterations in biochemical parameters and/or to functional impairment in
cirrhotic patients with and without hepatocellular carcinoma. METHODS: We studied
126 patients with liver cirrhosis, 60 of whom also had hepatocellular carcinoma.
CA19-9 values were related to clinical, biochemical and functional parameters. In
half of the patients CA19-9 levels were related to the monoethylglycinexylidide
test, which is a dynamic liver function test. RESULTS: In more than half the
cases CA19-9 values were above the upper limit. Liver function worsening as
assessed by Child-Pugh's score and monoethylglycinexylidide test did not seem to
influence the alteration of the marker. By contrast, in univariate analysis CA19
9 correlated with aminotransferases, gamma-glutamyltransferase and alkaline
phosphatase. Multivariate analysis showed that besides alkaline phosphatase also
the presence of hepatocellular carcinoma might influence the alteration of CA19
9, although the marker was of no use for the diagnosis of liver cancer in
patients with altered though not diagnostic alpha-fetoprotein levels.
CONCLUSIONS: In our study we confirmed the correlation of CA19-9 levels with
cholestasis and cytolysis parameters. Moreover, we found no association between
CA19-9 levels and impaired liver function as assessed by means of the Child
Pugh's score and the monoethylglycinexylidide test, which is cholestasis
independent and explores liver metabolic and clearance activities. The
cholestatic picture that characterizes liver cirrhosis might enhance the
expression and passage of the marker from the bile to the blood. The addition of
CA19-9 assessment is not useful for the diagnosis of hepatocellular carcinoma in
patients with non-diagnostic levels of alpha-fetoprotein. Caution should
therefore be used when evaluating CA19-9 in cirrhotic patients with cholestasis,
since false positive results may occur.
PMID- 11012099
TI - C-erbB-2 oncoprotein content in gastric cancer and in adjacent mucosa.
AB - The aim of this study was to evaluate, by means of an immunoenzymatic assay, the
membranous and cytosolic c-erbB-2 oncoprotein contents in primary tumors and in
adjacent mucosa from gastric cancer patients. Fifty-two patients with primary
gastric adenocarcinomas were enrolled in this prospective study. c-erbB-2 protein
levels were significantly higher in membranous than in cytosolic samples, both in
neoplastic tissues (median: 3602 vs 525 NHU/mg protein; p<0.0001) and in adjacent
mucosa samples (median: 3174 vs 509 NHU/mg protein; p<0.0001). Nevertheless,
there was a significant positive relation between membranous and cytosolic c-erbB
2 protein contents in both neoplastic tissue (p<0.001) and adjacent mucosa
(p<0.001) samples. There was no significant difference in the membranous c-erbB-2
protein content between neoplastic tissues and adjacent mucosa samples. However,
the cytosolic c-erbB-2 content was significantly higher in neoplastic tissues
than in adjacent mucosa (p<0.05). Finally, the results did not show any
significant correlations of these oncoprotein contents with patient
characteristics, clinicopathologic parameters and overall survival of the study
population.
PMID- 11012100
TI - Clinical evidence for correlation of insufficient tissue oxygen supply (hypoxia)
and tumor-associated proteolysis in squamous cell carcinoma of the head and neck.
AB - Hypoxic tumors of patients with squamous cell carcinoma of the head and neck show
a consistent trend towards poor treatment outcome. We now report that tumor
hypoxia in these patients is correlated with elevated antigen content of the
tumor-associated serine protease uPA (urokinase-type plasminogen activator), a
marker of tumor cell invasion and metastasis.
PMID- 11012101
TI - Towards a "good" death: end-of-life narratives constructed in an intensive care
unit.
AB - End-of-life decisions regarding the withdrawal and withholding of life supporting
technology have become commonplace within intensive care units (ICUs). In this
paper, we examine the dialogue between ICU team members and families regarding
limitation of treatment as a therapeutic narrative--that is, as a story which
frames therapeutic events as well as the critically ill patient's experience in a
meaningful and psychologically comforting way for families and health care
providers alike. The key themes of these end-of-life narratives are discussed, as
well as the qualities that the stories share with other narratives of the same
genre.
PMID- 11012102
TI - Cultural identity and illness: Fulani views.
AB - Cultural identity--who the Fulani think they are--informs thinking on illnesses
they suffer. Conversely, illness, so very prevalent in sub-Saharan Africa,
provides Fulani with a constant reminder of their distinctive condition in
Guinea. How they approach being ill also tells Fulani about themselves. The
manner in which Fulani think they are sick expresses their sense of difference
from other ethnic groups. Schemas of illness and of collective identity draw
deeply from the same well and web of thoughts. Three different approaches of
schema theory are used to trace what ties illness to identity. These are 1) the
schema as prototype; 2) a connectionist approach associates schemas for illness
with other cultural schemas; and 3) a hierarchy of schemas. The hierarchy
includes master schemas for ethnic identity, schemas for illness generally and
sub-schemas for separate ailments. Schemas orient and provide a framework for the
practice of being Fulani--in the sense that Bourdieu would describe practice as
the application of practical knowledge. Illnesses above the waist are said to be
part of the Fulani condition of belonging in arid climates while they need suffer
the humidity of Guinea. Illnesses below the waist are thought to arise when one
does not act like a Fulani, especially in matters of food and sex. As individuals
disclose or conceal illness, as they discuss illness and the problem of others
they reflect standards of Fulani life--being strong of character not necessarily
of body, being disciplined, rigorously Moslem, and leaders among lessors. To
disregard standards or to suggest one does not care about such standards is
shameful and places one out of phase with others and with cultural norms. But to
be in step with others and with cultural norms is to have pride in the self and
the foundations of Fulani life.
PMID- 11012103
TI - False teeth and real suffering: the social course of 'germectomy' in eastern
Uganda.
AB - The removal of the incipient canine teeth ('germectomy') in small babies is a
practice carried out in many parts of eastern Africa. This article describes how
'germectomy' among the Jop'Adhola in Eastern Uganda is an important idiom of
distress, referred to as false teeth by English speaking people, and lakijo
marach (bad teeth) or gira kwanya (that which is removed) in the local language
Dhop'Adhola. Through an analysis of how the notion of false teeth is shaped by
macro social forces of war and poverty as well as by negotiations within the
local social world, the discussion is taken beyond the question of cultural
belief. False teeth as a practice seems to have spread through vast geographical
areas within a few decades, but as the example of the Jop'Adhola shows, it has
taken a particular social course in eastern Uganda--as it is most likely to also
have done everywhere else it has gained a footing. By analyzing its social course
we may gain insight into important mediating social processes which may have as
much to do with actual health outcome in a particular area as health care per se.
PMID- 11012104
TI - Latinas, amniocentesis and the discourse of choice.
AB - Little attention has been paid to the impact of the increasingly routine use of
fetal diagnosis on how U.S. minority women experience their pregnancies and
decide whether to have their fetuses tested. Using narrative analysis, we offer
the account of one Latina who, despite considerable turmoil, ultimately accepted
an offer of amniocentesis. We describe her reasoning in choosing a course of
action. Data from interviews with 147 Latinas who were faced with the same
decision are used to contextualize the case study material. We seek to illuminate
how a blending of Mexican and European American cultural influences helped shape
the woman's experience and define the dilemma she faced when she learned her
fetus might be born with a grave or incurable condition because she was
ideologically opposed to abortion.
PMID- 11012105
TI - Balloon dilation of cor triatriatum dexter in a dog.
PMID- 11012106
TI - The case for measuring plasma colloid osmotic pressure.
PMID- 11012107
TI - Measurement of plasma colloid osmotic pressure in normal thoroughbred neonatal
foals.
AB - A normal plasma colloid osmotic pressure (COP) interval was established for foals
and compared to values for adult horses. Plasma samples were obtained from 38
Thoroughbred foals that had normal findings on postfoaling examination and 10
healthy Thoroughbred adult horses. Samples were analyzed using a commercially
available colloid osmometer. Fifty samples were obtained from 38 foals. Twelve
foals had 2 samples taken, 1 during the 1st 24 hours of life and the 2nd between
24 and 72 hours of life. For foals with 2 samples, only 1 randomly selected value
was used in group analysis. Total plasma protein, albumin, and globulin
concentrations were measured on all samples from foals. The mean measured plasma
COP for foals was 18.8 +/- 1.9 mm Hg for the 38 samples analyzed. Measured plasma
COP did not differ significantly over the time period examined for either the 12
paired samples (P = .13) or with regression analysis of the 38 samples (P = .13).
Calculation of mean COP, based on previously published quadratic equations using
total protein, albumin, and globulin concentrations, underestimated mean measured
foal COP values except for when total protein measured by refractometer was used
in the Landis-Pappenheimer equation. In conclusion, the plasma COP interval (95%
CI: 15.0 mm Hg, 22.6 mm Hg) obtained for healthy foals in this study was found to
be lower than that of healthy adult Thoroughbreds (20.6 +/- 0.7 mm Hg, P = .006).
PMID- 11012108
TI - Treatment of canine hemangiosarcoma: 2000 and beyond.
AB - Canine hemangiosarcoma (HSA) is an aggressive and malignant neoplasia with a
grave prognosis. Surgery and chemotherapy have limited success in prolonging
survival times and increasing quality of life in dogs with HSA. Advances in
medical oncology are resulting in increased survival rates and a better quality
of life for veterinary cancer patients. An understanding of mechanisms of
metastasis has led to the development of new treatments designed to delay or
inhibit tumor spread. Promising new treatment options include novel delivery
systems (inhalation or intracavitary chemotherapy); use of immunomodulators such
as liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine;
antimetastatic agents such as inhibitors of angiogenesis (interferons,
thalidomide), matrix metalloproteinase inhibitors, and minocycline; dietary
modifications; and gene therapy. Inhibitors of angiogenesis seem to be safe and,
unlike conventional chemotherapy, do not induce drug resistance. Although many of
the newer approaches are still under development and review, the use of
multimodality therapy incorporating innovative treatment modalities may offer the
best therapeutic option for dogs affected with HSA.
PMID- 11012109
TI - Prognostic factors in dogs with urinary bladder carcinoma.
AB - Medical records and biopsy specimens were retrospectively reviewed from 25 dogs
diagnosed with unresectable urinary bladder carcinoma and treated with
chemotherapy. Our intention was to identify clinical, histologic, and
immunohistochemical indicators of prognosis. Immunohistochemical stains for P
glycoprotein, glutathione-S-transferase pi, and factor VIII-related antigen were
applied to archived tissue. There were more spayed female dogs than castrated
male dogs (76% versus 24%). Transitional cell carcinoma was the most common tumor
(88%, n = 22), followed by undifferentiated carcinoma (8%, n = 2) and squamous
cell carcinoma (4%, n = 1). Overall median survival was 251 days. Histologic
diagnosis and immunohistochemical characteristics did not correlate with
prognosis. Spayed females survived significantly longer than castrated males (358
days versus 145 days, P = .042). Dogs that received either doxorubicin or
mitoxantrone in addition to a platinum-based chemotherapeutic (either cisplatin
or carboplatin) lived significantly longer than those that received only a
platinum compound (358 days versus 132 days, P = .042).
PMID- 11012110
TI - Primary myelodysplastic syndromes of dogs: a report of 12 cases.
AB - Clinical bone marrow specimens submitted to the University of Minnesota's
Veterinary Teaching Hospital Cytology Service over a 3-year period were evaluated
for the presence of myelodysplastic features. Of 220 bone marrow specimens
examined, 30 contained dysplastic features. Twenty-seven of these dogs were
evaluated further. Twelve were categorized as primary myelodysplastic syndromes,
and 15 were categorized as secondary myelodysplastic syndromes. Of the primary
myelodysplastic syndromes, 4 were subcategorized as refractory anemia and 8 were
categorized as myelodysplasia. Primary refractory anemia was characterized by
nonregenerative anemia without leukopenia or thrombocytopenia and with prolonged
survival. Primary myelodysplasia was characterized by pancytopenia, greater than
5% myeloblasts in bone marrow, dysplastic features in all bone marrow cell lines,
and short survival time. Results of this study indicate that differentiating
primary refractory anemia from primary myelodysplasia has both therapeutic and
prognostic significance. Dogs with primary refractory anemia tend to have
prolonged survival and respond to erythropoietin treatment, whereas dogs with
primary myelodysplasia have short survival and do not respond to standard
treatments.
PMID- 11012111
TI - Cisplatin and doxorubicin combination chemotherapy for the treatment of canine
osteosarcoma: a pilot study.
AB - Sixteen dogs with histologically confirmed appendicular osteosarcoma were treated
by amputation followed by cisplatin and doxorubicin chemotherapy. All dogs began
chemotherapy within 24 hours of surgery. Cisplatin was administered at 50 mg/m2
intravenously (IV) concurrent with saline-induced diuresis. Doxorubicin was
administered 24 hours later at 15 mg/m2 as a slow IV bolus. This protocol was
given on a 21-day cycle for 4 cycles. No dose delays were required, but dose
reduction of doxorubicin was required in 2 dogs because of neutropenia. Thoracic
radiography was performed every 2 months after completion of therapy to monitor
for metastatic disease. Two dogs were still alive and free from disease at the
time of last contact (24 and 75 months, respectively). Postmortem examinations
were performed on 13 of the 14 dogs that died. Eight of these dogs were
euthanized because of metastatic osteosarcoma. Of the remaining 5 dogs,
euthanasia was performed because of complications of idiopathic megaesophagus (n
= 1), arthritis (n = 2), and hemangiosarcoma (n = 2). The median disease-free
interval and survival times were 15.7 and 18 months, respectively. When compared
to a historical group of 36 dogs with appendicular osteosarcoma treated with
surgery and 4 doses of cisplatin. both disease-free interval and overall survival
were significantly longer in the study population (P < .015 and P < .007,
respectively).
PMID- 11012112
TI - Thiopurine methyltransferase in red blood cells of dogs, cats, and horses.
AB - Our objective was to determine if thiopurine methyltransferase (TPMT), the enzyme
important in the metabolism of azathioprine in human beings, is detectable in red
blood cell lysates (RBCL) of healthy dogs, cats, and horses. Values for TPMT
activity were determined from blood collected from 20 healthy dogs, cats, and
horses. The TPMT activity in each animal's RBCL was determined using a
radioenzymatic end point involving TPMT-facilitated metabolism of 6
mercaptopurine to 6-methylmercaptopurine (6-MMP). One unit of TPMT activity
represents the formation of 1 nmol of 6-MMP per milliliter of packed red blood
cells per hour of incubation at 37 degrees C. TPMT activity in RBCL was
detectable in all species, with mean RBC values +/- standard deviation of 17.9 +/
3.79 U/mL in dogs; 2.76 +/- 0.70 U/mL in cats; and 2.185 +/- 0.36 U/mL in
horses. Values for TPMT in the 3 species were significantly (P < .05) different
from one another. TPMT values for dogs were significantly higher than the other
species, and TPMT values for cats were significantly higher than those for
horses. We conclude that RBCL TPMT values are measurable in dogs. cats, and
horses and that dogs have higher values than cats or horses. These findings are
consistent with the lower tolerance for azathioprine in cats as compared with
dogs. It remains to be determined whether RBCL TPMT values in these species
correlate with TPMT activity in the liver, where most of the metabolization of
azathioprine is believed to occur.
PMID- 11012113
TI - Serum alhpa 1-acid glycoprotein concentrations in healthy and tumor-bearing cats.
AB - The purpose of this study was to evaluate alpha 1-acid glycoprotein (AGP)
concentrations in tumor-bearing and healthy cats. The hypothesis of the present
study was that AGP concentrations would be significantly increased in tumor
bearing cats. Serum from 51 healthy and 97 tumor-bearing, client-owned cats was
harvested at the time of presentation and stored at -80 degrees C until assayed.
Cats with measurable, histologically confirmed malignancies, and healthy cats of
similar ages were included. Serum was assayed for AGP concentration by using a
radial immunodiffusion method. AGP concentrations were significantly (P = .0051)
higher in tumor-bearing (763 +/- 595 microg/mL; mean +/- SD) when compared to
healthy cats (501 +/- 377 microg/mL; mean +/- SD). Of the tumor-bearing cats, 35
had carcinomas, 33 had sarcomas, and 26 had discrete, round cell tumors. AGP
concentrations were 645 +/- 62 microg/mL, 660 +/- 540 microg/mL, and 967 +/- 860
microg/mL, respectively, and there were no significant differences among the
groups.
PMID- 11012114
TI - Plasma homocysteine, B vitamins, and amino acid concentrations in cats with
cardiomyopathy and arterial thromboembolism.
AB - Arterial thromboembolism (ATE) is a common complication of cats with
cardiomyopathy (CM), but little is known about the pathophysiology of ATE. In
people, high plasma concentrations of homocysteine and low B vitamin
concentrations are risk factors for peripheral vascular disease. In addition, low
plasma arginine concentrations have been linked to endothelial dysfunction. The
purpose of this study was to compare concentrations of homocysteine, B vitamins,
and amino acids in plasma of normal cats to those of cats with CM and ATE. Plasma
concentrations of homocysteine, vitamin B6, vitamin B12, folate, and amino acids
were measured in 29 healthy cats, 27 cats with CM alone, and 28 cats with both CM
and ATE. No differences were found between groups in homocysteine or folate. Mean
vitamin B12 concentration (mean +/- standard deviation) was lower in cats with
ATE (866 +/- 367 pg/mL) and cats with CM (939 +/- 389 pg/mL) compared with
healthy controls (1,650 +/- 700 pg/mL; P < .001). Mean vitamin B6 concentration
was lower in cats with ATE (3,247 +/- 1.215 pmol/mL) and cats with CM (3,200 +/-
906 pmol/mL) compared with healthy control animals (4,380 +/- 1,302 pmol/mL; P =
.005). Plasma arginine concentrations were lower in cats with ATE (75 +/- 33
nmol/mL) compared with cats with CM (106 +/- 25 nmol/mL) and healthy control
animals (96 +/- 25 nmol/ mL; P < .001). Vitamin B12 concentration was
significantly correlated with left atrial size. We interpret the results of this
study to suggest that vitamin B12 and arginine may play a role in CM and ATE of
cats.
PMID- 11012115
TI - Clinical, echocardiographic, and neurohormonal effects of a sodium-restricted
diet in dogs with heart failure.
AB - The use of low-sodium diets in dogs with heart failure is common practice, but
randomized, double-blind studies have not been conducted to examine the benefits
or problems with this approach. The purpose of this study was to determine the
effects of a low-sodium diet on clinical, echocardiographic, and neurohormonal
parameters in dogs with heart failure. Dogs with stable chronic heart failure
were fed exclusively a low-sodium (LS) and a moderate-sodium (MS) diet for 4
weeks each in a randomized, double-blind, crossover design. At days 0, 28, and
56, echocardiography and thoracic radiography were performed, and blood was
analyzed for electrolytes and neurohormones. Fourteen dogs completed the study (9
with chronic valvular disease and 5 with dilated cardiomyopathy). Electrolyte
abnormalities were common during the study, and serum sodium and chloride
concentrations decreased significantly on the LS diet. Neurohormones did not
change significantly between diet groups. Maximum left atrial (P = .05) and
standard left atrial (P = .09) size decreased on the LS diet. For dogs with
chronic valvular disease, vertebral heart score (P = .05), left ventricular
internal dimension in diastole (P = .006) and systole (P = .02), standard left
atrial dimension (P = .03), maximum left atrial dimension (P = .02), end
diastolic volume index (P = .02), and end-systolic volume index (P = .04)
decreased significantly on the LS diet compared to the MS diet. Although analysis
of these data suggests some benefits of a low-sodium diet, future studies with
improved study design are needed to further evaluate the advantages and
disadvantages of sodium restriction in dogs with heart failure.
PMID- 11012116
TI - Cats surviving natural infection with Cytauxzoon felis: 18 cases (1997-1998).
AB - Eighteen cats surviving natural infection with Cytauxzoon felis were identified.
All cats came from a limited geographic area in northwestern Arkansas and
northeastern Oklahoma. Clinical signs in most cats were similar to those
described for cytauxzoonosis; however, 4 cats were asymptomatic. All cases were
initially diagnosed by microscopic identification of signet ring-shaped
piroplasms in erythrocytes of peripheral blood smears. Four of 4 cats tested had
detectable serum antibodies to C felis. Four different cats were positive by
polymerase chain reaction (PCR). Partial sequencing of the PCR product from 1 cat
revealed >99% homology with the reported sequence of C felis. Repeated
examination of blood smears from 12 cats revealed that the erythroparasitemia was
generally persistent for the duration of follow-up (3-154 days). Survival did not
seem dependent on treatment, as only 1 cat was treated with a drug with potential
antiprotozoal activity (imidocarb dipropionate), and 4 cats received no
treatment. The findings of this study may indicate the existence of a less
virulent strain of C felis.
PMID- 11012117
TI - Effects of enalapril versus placebo as a treatment for canine idiopathic
glomerulonephritis.
AB - A blinded, multicenter, prospective clinical trial assessed the effects of
enalapril (EN) versus standard care in dogs with naturally occurring, idiopathic
glomerulonephritis (GN). Twenty-nine adult dogs with membranous (n = 16) and
membranoproliferative (n = 13) GN were studied. Dogs were randomly assigned to
receive either EN (0.5 mg/kg PO q12-24h; n = 16) or placebo (n = 14) for 6 months
(1 dog was treated first with the placebo and then with EN). All dogs were
treated with low-dose aspirin (0.5-5 mg/kg PO q12-24h) and fed a commercial diet.
At baseline, serum creatinine (SrCr), systolic blood pressure (SBP), and
glomerular histologic grade were not different between groups, but the urine
protein/creatinine ratio (UP/C) was greater in the EN group compared with the
placebo group (8.7 +/- 4.4 versus 4.7 +/- 2.3). After 6 months of treatment, the
change in UP/C from baseline was significantly different between groups (EN =
4.2 +/- 1.4 versus 1.9 +/- 0.9 in the placebo group). When data were adjusted for
changes in SrCr (SrCr X UP/C) a similar significant reduction was noted ( 2.2 +/-
15.2 versus 8.4 +/- 10.1). The change in SBP after 6 months of treatment also was
significantly different between groups (EN = -12.8 +/- 27.3 versus 5.9 +/- 21.5
mm Hg in the placebo group). Response to treatment was categorized as improvement
(assigned a value of 2), no progression (assigned a value of 1), and progression
(assigned a value of 0). Response was significantly better in the EN group (1.4
+/- 0.8) compared with the placebo group (0.3 +/- 0.5). These results suggest
that EN treatment is beneficial in dogs with naturally occurring idiopathic GN.
PMID- 11012118
TI - Quantitative bacterial cultures and cytological examination of bronchoalveolar
lavage specimens in dogs.
AB - Cytology and quantitative bacterial cultures of lower respiratory tract
secretions are widely used in human medicine to differentiate airway infection
from simple bacterial colonization. A retrospective study was conducted to
determine the usefulness of quantitative aerobic cultures and Gram stain
intracellular bacteria counts from bronchoalveolar lavage (BAL) specimens in dogs
in diagnosing lower respiratory tract infection (LRTI) and to determine whether
chronic bronchitis is associated with marked bacterial growth in dogs. The
threshold determined to define clinically relevant bacterial growth was 1.7 x
10(3) colony-forming units per milliliter of BAL fluid. We used this threshold
and found that diagnostic sensitivity and specificity were 86% and 100%,
respectively. With a threshold for infection of >2 intracellular bacteria
observed in any of 50 fields, microscopic examination of Gram stain BAL
preparations had a sensitivity of 71% and a specificity of 97% in establishing
LRTI. There was a high correlation between bacterial morphology on BAL Gram stain
and bacterial cultures. Combining the results of intracellular bacteria counts
from the BAL Gram stain with those from the quantitative cultures, the
sensitivity in diagnosing LRTI was 87% and the specificity was 97%. BAL
quantitative cultures as well as quantitating intracellular bacteria on Gram
stain BAL cytology were revealed to be useful in identifying LRTI in dogs.
Chronic bronchitis does not appear to be associated with marked bacterial growth
in dogs.
PMID- 11012119
TI - Reduced serum insulin-like growth factor (IGF) and IGF-binding protein-3
concentrations in two deerhounds with congenital portosystemic shunts.
PMID- 11012120
TI - Pulmonary alveolar proteinosis in a dog.
PMID- 11012121
TI - Demonstration of thiopurine methyltransferase activity in the erythrocytes of
cats.
AB - Azathioprine is a purine analogue used as an immunosuppressive and
immunomodulator agent in various mammals, including cats. Several adverse
reactions have been reported and have limited the use of the drug in the cat.
Adverse reactions to azathioprine in humans have been correlated with reduced
activity of thiopurine methyltransferase (TPMT) in erythrocytes. The purpose of
this preliminary study was to determine if cats have TPMT activity in their
erythrocytes and to compare the values obtained with the normal range for humans
and the normal range for dogs in a preliminary report. Activity of the enzyme was
measured in blood samples drawn from 41 cats. Blood also was taken from 5 dogs.
The mean erythrocyte TPMT activity in the cats was 2.4 +/- 0.4 nmol (range, 1.2
3.9 nmol) per hour per milliliter of red blood cells (U/mL RBC) or 2-8 nmol per
hour per gram of hemoglobin (U/g Hb). This range was far lower than the normal
human range (8-15 U/mL RBC; 16-33 U/g Hb) and was of monopolar distribution. This
observation apparently precludes any diagnostic purpose in assaying erythrocyte
TPMT in this species. Erythrocyte TPMT activity in the 5 dogs ranged from 5.5 to
13.1 U/mL RBC (11-27 U/g Hb), which was comparable with normal and carrier ranges
for humans, but proof of TPMT genetic polymorphism in either species will require
genotyping studies.
PMID- 11012122
TI - Enabling the quality in care.
PMID- 11012123
TI - Unilateral neonatal testicular torsion.
AB - Testicular torsion in the neonatal period is an unusual finding. Because of the
high morbidity associated with this condition, early recognition and appropriate
management are imperative. Testicular torsion may be unilateral or bilateral and
may occur prenatally or in the early postnatal period. Often, the nurse is the
first health care provider to examine a newborn after birth and must be aware of
the signs of this condition to minimize the risk of testicular loss.
PMID- 11012124
TI - Is motherhood good for women? A feminist exploration.
AB - Motherhood as biologic destiny for women, has been long assumed. As nurses who
aid women struggling with the demands of career and motherhood, we need to
question this assumption. An exploration of feminist theory offers nurses ideas
(and perhaps permission) to question the purpose and effects of mothering and the
effects of mothering on women in our culture. Additionally, parallels between
motherhood and the nursing profession are drawn.
PMID- 11012125
TI - An inpatient cervical cancer screening program to reach underserved women.
AB - Underserved women (e.g., African American, older women of all races) are less
likely to be screened than other groups. The Johns Hopkins Hospital began the
Cervical Cancer Screening Program (CCSP) to provide direct Papanicolaou (Pap)
test screening to inpatient females. Over a 1-year period, 256 women received Pap
tests as part of the CCSP. Of these, 56% (n = 144) were African American, 36% (n
= 92) received medical assistance benefits, and only 47% (n = 120) had health
insurance. The CCSP is an effective way to screen low-income and underserved
females who otherwise may not be screened.
PMID- 11012126
TI - Prenatal perineal massage: preventing lacerations during delivery.
AB - OBJECTIVE: To investigate the associations between perineal lacerations and 13
variables associated with the incidence of perineal lacerations. Of particular
interest was the variable of prenatal preparation of the perineum. DESIGN: This
retrospective descriptive study used a convenience sample of 368 women whose
delivery was attended by at least one of two midwives practicing in the Northwest
between 1979 and 1995. SETTING AND PARTICIPANTS: All births in the study occurred
in a home-based midwifery practice in the Northwest. The sample was primarily
white and included 307 multiparous and 61 primiparous women. MAIN OUTCOME
MEASURES: The initial chi squares indicated that five of the 13 factors
investigated were significantly associated with the degree of laceration: parity,
maternal age, maternal position at delivery, length of second stage of labor, and
prenatal perineal massage. However, further analyses showed that when parity was
controlled, the only factors independently associated with the seriousness of
lacerations were parity and prenatal perineal massage. CONCLUSION: This study
supports the conclusion that teaching perineal massage to primiparous women and
multiparae who had episiotomies with their previous births is a useful
intervention. It suggests that further study may help clarify the optimum
frequency, timing, and technique of massage.
PMID- 11012127
TI - Experienced obstetric nurses' decision-making in fetal risk situations.
AB - OBJECTIVE: To determine which clinical factors experienced obstetric nurses
consider most important in determining fetal risk during the intrapartum period.
DESIGN: Ten dichotomized variables relevant to participants' clinical decision
making were manipulated in fractional factorial vignettes. Participants were
asked to rate the severity of fetal risk on a Likert scale after reading the
vignettes. SETTING: About 87% of the participants worked in institutions with
4,000 or fewer deliveries per year. More than 25% worked in tertiary level
facilities, and the remainder were employed in primary or secondary level
facilities. PARTICIPANTS: Participants (N = 573), randomly selected from a list
of nurses certified in "inpatient obstetric nursing" by the National
Certification Corporation, were mailed the vignettes. The average number of years
of intrapartum nursing experience was 13. MAIN OUTCOME MEASURE: Multiple
regression analysis was used to determine the weights given to the 10 clinical
factors by participants. RESULTS: Fetal scalp pH, maternal parity, amniotic fluid
color, and long-term variability of the fetal heart rate were the most important
predictors of nurses' fetal risk assessments. CONCLUSIONS: Long-term variability
was the most important cardiotocographic factor in nurses' fetal risk assessments
and the only cardiotocographic factor of the best 4 predictors of fetal risk.
This indicated that participants were realistic about the limitations of
electronic fetal monitoring (EFM).
PMID- 11012128
TI - Identifying labor support actions of intrapartum nurses.
AB - OBJECTIVE: To identify specific nursing actions that best characterize labor
support from the nurse's perspective. DESIGN: A descriptive survey design using a
three-round Delphi technique was used to explore the views of intrapartum nurses
in the United States related to labor support. PARTICIPANTS: Five hundred AWHONN
members who identified themselves as intrapartum nurses were invited to
participate in the survey. One hundred eighty-six nurses agreed to participate.
Participants who submitted usable surveys in each round: round one, n = 166;
round two, n = 115; and round three, n = 117. Eighty-seven nurses participated in
all three rounds of the survey. RESULTS: The participants identified 55 specific
nursing actions as supportive care. These interventions ranged from psychosocial
support such as remaining with the mother if she is fearful to physical support
measures such as position changes. The nurses clearly distinguished between
supportive nursing care and the assessment and technical aspects of their job.
The nurses also identified the overall goals of intrapartum nursing were to
assure a safe outcome for the newborn (82.8% of participants) and for the mother
(75% of participants). CONCLUSIONS: The supportive actions identified by this
panel of intrapartum nurses were similar to ones identified by mothers in other
studies. Nurses made a clear distinction between supportive nursing care and
assessment skills or technical tasks.
PMID- 11012129
TI - The circadian rhythm of blood pressure during pregnancy.
AB - OBJECTIVE: To review the literature on the circadian rhythm of blood pressure
during pregnancy. DATA SOURCES: Computerized searches on MEDLINE, CINAHL, and
MIRLYN. STUDY SELECTION: Selected studies from 1 969 to 1997 were evaluated. DATA
EXTRACTION: Data were extracted and information was organized under the following
areas: definition of and the interconnection between circadian rhythm and blood
pressure; the circadian variability of blood pressure throughout the trimesters;
the patterns of the circadian rhythm of blood pressure in pregnancies defined as
normal and those complicated by chronic hypertension and preeclampsia; and
clinical implications. DATA SYNTHESIS: The circadian rhythm of blood pressure in
pregnancy is the same as in the non-pregnant state, with a nocturnal decrease,
especially during sleep. In patients with chronic hypertension, the nocturnal
fall in blood pressure may be steeper. Patients with mild preeclampsia may
experience a less pronounced nocturnal decrease in blood pressure. Patients with
severe preeclampsia may display a reversed circadian rhythm, with no decrease
and/or an increase in nocturnal blood pressure. CONCLUSIONS: The patterns of the
circadian rhythm of blood pressure during normal pregnancy and pregnancies
complicated by chronic hypertension and preeclampsia warrant consideration when
monitoring patients and implementing management plans.
PMID- 11012130
TI - The development of AWHONN's fetal heart monitoring principles and practices
workshop. Association of Women's Health, Obstetric and Neonatal Nurses.
AB - The Fetal Heart Monitoring Principles and Practices (FHMPP) workshop was designed
at the request of AWHONN's Committee on Education to meet member requests for
standardized education in fetal heart assessment, including didactic and
psychomotor skill content. Events and decisions are chronicled, from inception of
the FHMPP program to development, evaluation, and revision. Current statistics
and participation demonstrate the success of the workshop and its ongoing need.
Today, as the project continues to grow and improve, its primary strength lies in
member involvement and support.
PMID- 11012131
TI - Legal implications of fetal heart assessment.
AB - The standard of care requires perinatal nurses to perform fetal heart (FH)
assessment competently and safely. Failure to adhere to established guidelines
and standards for FH assessment may result in negative outcomes for the fetus or
newborn and contributes to claims of nursing negligence. The perinatal nurse must
be fully cognizant of professional guidelines and standards for FH assessment and
comply with agency policies and procedures when conducting assessment of the
fetal heart. Guidelines for FH assessment during the antepartum and intrapartum
period are discussed within the context of restructured health care settings and
today's medicolegal climate.
PMID- 11012132
TI - Computer analysis of the fetal heart rate.
AB - Computer analysis of the fetal heart rate is a technology of the Information Age
commercially available for research and clinical practice. Intelligent systems
are engineered with algorithms or neural networks designed to simulate expert
knowledge. Automated analysis has provided objective, standardized, and
reproducible data used to research fetal heart rate responses in the antepartum
and intrapartum setting. Perinatal information systems can integrate FHR analysis
and data management.
PMID- 11012133
TI - Fetal pulse oximetry: an adjunct to electronic fetal heart rate monitoring.
AB - Electronic fetal heart rate monitoring is routinely used as an indirect measure
of fetal oxygenation, yet its value continues to be questioned. With a
nonreassuring fetal heart rate pattern, the clinician often needs additional
information about fetal oxygen status. Fetal pulse oximetry is a new fetal
assessment technology. After consideration of the results of a multicenter
randomized, controlled, clinical trial on fetal pulse oximetry in the United
States, the U.S. Food and Drug Administration approved the technology for
clinical use on May 12, 2000. The results of this trial are anticipated to be
published in late 2000.
PMID- 11012134
TI - Hypoxic-ischemic encephalopathy.
AB - Cerebral hypoxia-ischemia (asphyxia) occurring in the fetus and newborn infant is
a major cause of acute mortality and chronic neurological disability in
survivors. This review highlights many practical aspects of perinatal hypoxic
ischemic brain damage, including neuropathological features, obstetrical
antecedents, and clinically important aspects of identification, management, and
prognosis. Diagnostic techniques, including neuro-imaging, to diagnose hypoxic
ischemic encephalopathy also are discussed. A thorough knowledge of the clinical
spectrum of perinatal hypoxic-ischemic encephalopathy should enable
neonatologists to undertake appropriate management strategies and prognostic
indicators.
PMID- 11012135
TI - Congenital chylothorax.
AB - The objective of this paper is a retrospective study of all infants treated for
congenital chylothorax at the Royal Children's Hospital (RCH), Melbourne,
Australia and King Fahad National Guard Hospital (KFNGH), Riyadh, Kingdom of
Saudi Arabia. The charts of all infants with congenital chylothorax admitted to
RCH over a period of 13 years, June 1982-August 1994, and admissions to KFNGH
over a 7-year period, June 1992-August 1998 inclusive, were reviewed including
management outcome and complications. There were 19 infants, 13 from RCH and 6
from KFNGH; 11 females and 8 males. Three infants were managed antenatally.
Fifteen infants presented immediately after birth. Seven were born with hydrops
fetalis, 6 infants had syndromes and 10 infants were born prematurely. Regular
infant feeding formula and/or breast milk were used successfully in 12 infants,
while in 7 infants medium chain triglycerides (MCT) rich formula was used.
Sixteen infants were mechanically ventilated with 75% of them ventilated for < or
= 28 days. Fifteen infants received total parenteral nutrition (TPN), and in 80%
for < or = 32 days. Hydropic infants had longer duration of mechanical
ventilation and hospital stay with mean (range) of 33.9 (3-120) and 115 (23-225)
days, respectively, compared with 18 (1-62) and 34.3 (14-88) days for nonhydropic
infants. Five infants underwent surgery with failure in four. Sepsis and
bronchopulmonary dysplasia were the main complications. The survival rate was
100% regardless of the mode of therapy. The prognosis of Isolated congenital
chylothorax in term, and preterm infants is good even in the presence of hydrops.
Breast milk and/or regular infant feeding formula should be used initially before
proceeding to MCT-rich formula, which may be necessary in some cases. Surgery
should be considered if conservative management of congenital chylothorax fails
after 4-5 weeks.
PMID- 11012136
TI - Association between epidural analgesia and intrapartum fever.
AB - The objective of this paper is to determine whether or not epidural analgesia is
an independent risk factor for intrapartum fever. Maternal temperature was
measured every 4 h during labor to 1004 consecutive women in term labor. Women
with fever or on antibiotics were excluded. Epidural analgesia was administered
upon patients' request. Of the 406 (40%) women who received epidural analgesia,
11.8% (n = 48) developed a fever > or = 37.8 degrees C during labor compared with
only 0.2% (n = 1) of women not receiving epidural analgesia. Women who received
epidural analgesia were more likely to have one or more risk factors for
intrapartum infection. Their labor and ruptured membranes were longer, they were
more likely to have internal monitoring and have more vaginal examinations.
Compared with women who received epidural analgesia and did not develop
intrapartum fever, women that did develop fever had longer epidurals and more
risk factors for infection. However, in a logistic regression analysis with fever
as dependent variable, only the duration of epidural was significantly associated
with the occurrence of fever. The rate of fever increased with longer labors,
from 5% with labor < 3 h to 28% with labor > 6 h. In 90% of women the fever
resolved within a few hours after delivery. Sepsis evaluation was negative in all
of the newborns to mother who had intrapartum fever. Our data support a
noninfectious etiology for intrapartum fever in the vast majority of our
patients. However, infection must be ruled out before a decision is made to
withhold antibiotic therapy.
PMID- 11012137
TI - Yield and costs of screening growth-retarded infants for torch infections.
AB - Many infants with intrauterine growth retardation (IUGR) are screened for TORCH
infections. The yield and costs of such a practice may not be justifiable.
Medical charts of infants with IUGR who had a workup for toxoplasmosis, other
(infections), rubella, cytomegalovirus (infection), and herpes (simplex) (titer)
(TORCH) infections were reviewed for the presence of clinical findings,
laboratory and head ultrasound abnormalities associated with intrauterine
infections. Maternal charts and reports of placental pathology were reviewed for
identifying maternal illnesses and placental causes associated with IUGR. Seventy
five out of 182 infants (41%) with IUGR had a workup for TORCH infection.
Maternal conditions associated with IUGR included: pregnancy-induced hypertension
(19%), tobacco use (43%), alcohol abuse (21%), illicit drug use (24%), chronic
hypertension, diabetic vasculopathy or collagen vascular disease (12%), and
multiple gestation (3%). Placental pathology was available in 53/75 cases. Thirty
six of fifty-three (67%) placentae had abnormalities associated with IUGR:
placental infarcts (22 of 36), vasculitis/villitis (15 of 36), placenta previa (1
of 36), abruptio placenta (2 of 36), and velamentous insertion of umbilical cord
(1 of 36). Clinical findings among infants included hepatosplenomegaly, cataract
or rash (1 of 75), thrombocytopenia and/or neutropenia and/or direct
hyperbilirubinemia (11 of 75). Seven out of 75 infants had dysmorphic features.
None of the infants (0 of 75) had positive IgM titers for toxoplasma, rubella,
cytomegalovirus (CMV), or herpes simplex virus (HSV). No infants (0 of 43) had
elevated total IgM titers; one infant (1 of 57) had a positive urine culture for
CMV. One infant had evidence of calcifications on head ultrasound and a second
infant had hydrocephalus (2 of 43). The costs associated with workup for TORCH
infections among 75 infants included: TORCH titers determination: $17,816, total
IgM titers: $1318, urine culture for CMV: $5734, and head ultrasound: $28,165.
The yield of workup for TORCH infection among infants with IUGR is poor and does
not justify the incurred costs.
PMID- 11012138
TI - Anemia during pregnancy and birth outcome: a meta-analysis.
AB - To determine the relationship between maternal anemia [hemoglobin (Hgb) < 10-11
g/dL] and various birth outcomes, a meta-analysis was conducted based on
published literature identified by MEDLINE and manual search from 1966 through
1999. Odds ratios (OR) from selected studies were pooled according to the
gestational age at anemia diagnosis. The meta-analysis shows that maternal anemia
during early pregnancy was associated with slightly increased preterm birth
[pooled adjusted OR (aOR): 1.32, 95% confidence interval (CI): 1.01-1.74], and
nonstatistically significant increased low birth weight [pooled aOR: 1.39 (0.70
2.74)], and was not associated with fetal growth restriction [pooled aOR: 1.01
(0.73-1.38)]. However, there was a nonstatistically significant inverse
relationship between anemia during late pregnancy and preterm birth [pooled aOR:
0.92 (0.54-1.84)] and low birth weight [pooled aOR: 0.80 (0.64-1.00)]. Anemia was
not statistically significantly associated with hypertensive disorders of
pregnancy regardless of stage of pregnancy [pooled OR: 0.80 (0.53-1.20)]. The
relationship between anemia and perinatal mortality was inconclusive. A few
studies indicated that severe maternal anemia (Hgb < 8-8.5 g/dL) was associated
with increased risk of poor outcomes. We conclude that early pregnancy anemia is
associated with slightly increased risk of preterm birth. The trend toward an
inverse association of anemia determined during late pregnancy with preterm birth
and low birth weight may reflect the benefit of plasma volume expansion.
PMID- 11012139
TI - Sandifer's syndrome in a breast-fed infant.
AB - Sandifer's syndrome is a rare manifestation of gastroesophageal reflux (GER) in
children, occurring in association with abnormal movements of the head, neck, and
upper part of the trunk. Out of 65 children with Sandifer's syndrome described in
literature, only 2 were breast-fed. We report on a 15-day-old breast-fed girl
affected by Sandifer's syndrome. Pathological GER was diagnosed with 24 h pH
esophageal monitoring. In our patient, all the symptoms of Sandifer's syndrome
disappeared when she was cow's milk formula-fed. The role of food allergy to
dietary proteins ingested by a lactating mother is discussed.
PMID- 11012140
TI - Severe aortic thrombosis in the neonate--successful treatment with low-molecular
weight heparin: two case reports and review of the literature.
AB - Small- to moderate-sized aortic thrombi in the sick newborn are frequently
demonstrated, however, severe aortic thrombosis is rarely encountered. We report
two newborn infants presenting with signs of decreased lower limb perfusion
shortly after birth. An occlusive infrarenal aortic thrombus was demonstrated in
both infants by ultrasound. No predisposing condition for thrombosis could be
found in the first infant; in the second, an umbilical arterial catheter was the
likely cause. The infants were successfully treated with low-molecular-weight
heparin. In both infants resolution of the thrombus was observed by ultrasound.
No complications of treatment were encountered. The clinical spectrum of neonatal
aortic thrombosis and treatment options are reviewed.
PMID- 11012141
TI - Variations in neutrophil count in preterm infants with respiratory distress
syndrome who subsequently developed chronic lung disease.
AB - Neutrophil counts were studied in 62 preterm infants receiving mechanical
ventilation for neonatal respiratory distress syndrome (NRDS). Exploratory
analysis indicated that the severity of NRDS, as demonstrated by fractional
inspired oxygen (FiO2), mean airway pressure (MAP), arterial-alveolar PO2 ratio
(a/APO2) and oxygenation index (OI), was correlated with percentage change of
neutrophil counts during the first 5 days of life. Further analysis demonstrated
that infants with NRDS who subsequently developed chronic lung disease (CLD) (n =
21) had statistically significant differences in variation of neutrophil counts
when compared with the remainder (n = 41) without CLD (-35.0% +/- 4.3 vs. -16.9%
+/- 5.8, p < 0.02). It is concluded that significant variations in neutrophil
counts during the first 5 days of life may be found in infants with NRDS who
subsequently develop CLD and that these changes may have predictive value
regarding the development of CLD.
PMID- 11012142
TI - Mode of delivery and neonatal hematocrit.
AB - The objective of this paper is to test the hypothesis that the 2-h hematocrit
(HCT) is lower in infants born by cesarean section (CS) than in infants born
vaginally and that the postnatal rise of HCT is lower in infants born by CS than
in infants delivered vaginally. We prospectively studied 31 infants delivered by
elective CS, 21 infants delivered by CS because of arrest of descent and 30
vaginally delivered (VD) infants. All pregnancies were term, uncomplicated in
nonsmoking mothers. Apgar scores were > 7 at 1 and 5 min. In all infants
umbilical cord was clamped early. Umbilical vein and 2-h peripheral venous micro
HCT were measured by centrifugation. Cord-blood HCT, 2-h HCT, and rise in HCT
were similar in the two CS groups and significantly lower than in the VD group.
In multiple regression, gestational age, Apgar score, or the presence or not of
labor did not influence cord-blood HCT, 2-h HCT, or the rise in HCT. Infants born
by CS have lower HCT than infants born vaginally. Prediction of 2-h HCT from cord
blood HCT must take into account the mode of delivery.
PMID- 11012143
TI - A tribute to Theodor M. Fliedner.
PMID- 11012144
TI - Regulatory mechanisms controlling hematopoiesis: principles and problems.
AB - Hematopoiesis is regulated by the combined action of specialized stromal cells
and a consortium of hematopoietic regulatory factors. The multiplicity of these
regulatory controls does result in overlapping regulator action, but multiple
regulators are required to stimulate stem cell proliferation and are more
efficient than single regulators when stimulation of progenitor cells is
required. Gene inactivation studies have indicated that despite overlapping
actions each hematopoietic regulator does have unique functions. Delayed
elevations of stem and progenitor cells in the blood are a feature of enhanced
hematopoiesis induced by the injection of regulators. These cells are not a
random sample of marrow cells in such situations and may well be selected to
rapidly amplify hematopoiesis by seeding previously inactive hematopoietic
regions.
PMID- 11012145
TI - The role of blood stem cells in hematopoietic cell renewal.
AB - It has been the purpose of this keynote address to review available evidence for
the notion that the stem and progenitor cells circulating in the peripheral blood
play a decisive role in the homeostasis of blood cell formation distributed
throughout dozens of bone marrow units in the skeleton. Furthermore, if this
notion is correct, one could speculate that the quantity and quality of stem and
progenitor cells in the blood should reflect the functional state of the
hematopoietic stem cell system throughout the skeletal bone marrow and provide a
new tool for the evaluation of alteration in blood cell production. On this
basis, the following questions are considered: A) What do we know about the
quality and quantity of blood stem cells in steady state conditions? B) In what
way do blood stem cells respond to perturbations of the "steady state" of blood
cell formation? C) Which role do blood stem cells play during hemopoietic
development assuming that the establishment of bone marrow hemopoiesis requires
the "seeding" of blood stem cells into an appropriate cellular environment? D)
What is the role of blood stem cells in hemopoietic regeneration after partial
body irradiation with a small volume of marrow (and hence stem cells) protected?
and E) What are the mechanisms and/or kinetics of hemopoietic recovery if stem
cells introduced into the circulation were collected from exogenous (autologous
or allogeneic) sources? In this review presentation, experimental work of our
group and of other members of the scientific community is summarized. It becomes
obvious that blood stem and progenitor cells play a key role in hematopoietic
homeostasis. Furthermore, their physiology and pathophysiology deserve rigorous
experimental studies in order to develop a novel tool in the diagnosis and
prognosis of neoplastic and non-neoplastic disorders of blood cell formation.
PMID- 11012146
TI - Phenotype of the engrafting stem cell in mice.
AB - The present data on engraftment into non-myeloablated mice strongly suggest that
engraftment is determined by host-donor ratios as opposed to opening space.
Theoretically, if the ratios of donor to host stem cells could be altered,
especially without causing toxicity to the host animal, then the phenotypic
readout could be increased in a clinically applicable manner. To research this
further, we investigated low-dose irradiation (100 cGy) for its effects on
marrow, spleen and peripheral blood counts, as well as engrafting stem cell
levels. We found a transient but significant depression in the white blood cell
and platelet counts in the peripheral blood which returned to normal by two
weeks, with no apparent deleterious effect on the animals. However, the same
irradiation dose after two months impaired marrow repopulation and reduced
engraftment potential to less than 20% capacity. These results suggested that we
could obtain much higher phenotypic readouts after engraftment with this model;
thus, we assessed the engraftment of 40 million male BALB/c marrow cells into
female hosts exposed to 100 cGy at two, five and eight months after cell
infusion. The resultant high levels of chimerism, reaching 100% in many cases,
strongly suggest that the key to engraftment in these models is host-donor stem
cell ratios. One important issue relative to the above finding is whether
cytokine-stimulated proliferating stem cells have irreversibly lost engraftment
capacity or whether changes in the engraftment capacity are of a plastic nature,
possibly related to cell cycle transit. A number of experiments following
engraftment have shown that the engraftment defect is reversible and can be
repeatedly lost and regained during the initial portions of a cytokine-stimulated
culture. The above results suggest that, at least at the more primitive stem cell
level, hematopoietic stem cell regulation may in part be based on a cell cycle
model rather than a hierarchical system.
PMID- 11012147
TI - Comparative effects of retroviral-mediated gene transfer into primary human
stromal cells of Flt3-ligand, interleukin 3 and GM-CSF on production of cord
blood progenitor cells in long-term culture.
AB - The effects of different cytokines on growth of human cord blood CD34 cells was
studied by performing long-term culture (LTC) with primary human stromal cells
transduced with genes for either Flt3-ligand (L) (human transmembrane, murine
soluble or murine membrane-bound forms), human interleukin 3 (IL-3) or human GM
CSF. Molecular analysis of genomic DNA from transduced stromal cells using neo
specific polymerase chain reaction demonstrated gene transfer of G418-selected
stromal cell populations. Enzyme-linked immunosorbent assay and biological assays
of conditioned media from transduced stromal cells indicated expression and
release of soluble cytokines. Numbers of both immature and more mature
progenitors (colony-forming unit-granulocyte, erythroid, macrophage,
megakaryocyte; CFU-GEMM, BFU-E, CFU-GM) were increased threefold compared to
control in the Flt3-L (transmembrane) LTC throughout five weeks of culture. IL-3
and GM-CSF feeders increased progenitor cell output also, but these effects were
significantly lower than Flt3-L feeders. The two Flt3-L isoform engineered
feeders, Ex6 (soluble isoform) and 5H (membrane-bound isoform), showed a
decreased effect compared to the transmembrane Flt3-L feeders and, in particular,
Ex6 feeders were similar to control feeders and 5H feeders were comparable to
Flt3-L feeders only in the first two weeks of LTC. These results were apparent
also by limiting dilution assays that showed a higher frequency of pre-CFU in the
transmembrane Flt3-L feeders compared to control and the other cytokine feeders.
Exogenous addition of soluble growth factors to suspension cultures without
feeder layers, while superior to stromal feeders for short-term expansion of
early progenitors, were inferior to the long-term maintenance/output on stromal
feeders. Pre-CFU analysis supported these data. These results may be of some
significance to understanding the actions of Flt3-L on blood cell production.
PMID- 11012148
TI - Unilineage hematopoietic differentiation in bulk and single cell culture.
AB - The rarity of hematopoietic stem and progenitor cells (HSCs, HPCs) has hampered
the analysis of cellular and molecular mechanisms underlying early hematopoiesis.
Methodology for HPC purification has partially offset this limitation. A further
hurdle has been represented by the heterogeneity of the analyzed HPC/precursor
populations: recently, development of unilineage HPC differentiation cultures has
provided homogeneous populations of hematopoietic cells, particularly in the
early differentiation state, i.e., populations pertaining to a single lineage and
a restricted stage of differentiation/maturation, but sufficiently large for
cellular/molecular analysis. This report focuses on the development and
characterization of the unilineage HPC differentiation culture systems. A section
is devoted to selected cellular and molecular mechanisms underlying
hematopoiesis, which have been investigated by the HPC unilineage culture
approach. Finally, recent advances in the development of HPC unilineage cultures
at single cell level are discussed.
PMID- 11012149
TI - Differences between normal and CML stem cells: potential targets for clinical
exploitation.
AB - Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder in which
there is a deregulated amplification of CML progenitors at intermediate stages of
their differentiation along the myeloid, erythroid and megakaryocyte pathways.
Such cell populations are routinely quantified using standard in vitro colony
forming cell (CFC) assays. The excessive production of leukemic CFC that is seen
in most CML patients at diagnosis may be explained at least in part by their
increased proliferative activity. An anomalous cycling behavior in vivo has also
been found to extend to more primitive CML progenitor populations detectable as
long-term culture-initiating cells (LTC-IC). Although the molecular basis of
these changes in CML progenitor regulation is not fully understood at the level
of the primitive CFC compartment, a selective inability of CML progenitors to be
inhibited by certain -C-C-type chemokines has been demonstrated. Failure of the
CML stem cell compartment to expand in vivo at the same rate as later progenitor
cell types may be explained by their unique additional possession of an
intrinsically upregulated probability of differentiation. Such a mechanism would
be consistent with the observed loss of LTC-IC activity by CML cells incubated in
vitro under conditions that sustain or expand normal LTC-IC populations. Initial
clinical studies undertaken at our center established the feasibility of
exploiting the differential behavior of primitive normal and CML cells in vitro
as a potential purging strategy for reducing the leukemic stem cell content of
CML marrow autografts. The results of a larger, second trial now in progress on a
group of unselected patients are encouraging. Future studies of nonobese
diabetic/severe-combined immunodeficiency mice engrafted with CML cells should
provide another useful preclinical model for evaluating treatments that may more
effectively eradicate the neoplastic clone in vivo.
PMID- 11012150
TI - Maturation hierarchy of leukemic stem cells.
AB - Here we discuss the characteristics of various progenitor cell assays for human
acute myeloid leukemia (AML) with emphasis on the repopulating properties of
human AML progenitor cells, their potential relevance for pathophysiological
studies, and treatment development in AML.
PMID- 11012151
TI - Human hematopoietic progenitor in bone marrow and peripheral blood.
AB - The ability to enhance the frequency of progenitors in the peripheral circulation
has resulted in peripheral blood progenitor cell collections being the preferred
procurement method for autologous transplants and an accepted alternative for
allografts. In autografts, peripheral blood-derived progenitor cells appear to
have an advantage over conventional marrow transplants in the form of earlier
engraftment without compromising sustained marrow function. Studies were
performed to evaluate the broad class of CD34+ progenitors and their subtypes in
preparations of bone marrow and peripheral blood cells. As a result, peripheral
blood appears to contain a larger quantity of more mature progenitors, which is
the likely reason for a more rapid return of granulocytes and platelets. However,
controveries continue to exist as to whether the measurements derived from these
studies can be used to predict time to engraftment and subsequent reestablishment
of a marrow reserve. Some of these issues have been addressed in pilot studies
where allografts using G-CSF-mobilized peripheral blood progenitor cells were
compared to conventionally harvested bone marrow and bone marrow obtained from G
CSF-stimulated donors. The time to engraftment of neutrophils and platelets were
shortened when G-CSF-mobilized peripheral blood or marrow progenitor cells were
used compared to case-matched grafts of steady-state marrow. The significance of
the suggested differences between steady-state bone marrow grafts and mobilized
peripheral blood cells remains to be determined. However, preparations of
cytokine-mobilized peripheral blood progenitor cell preparations are being used
with increasing frequency to replace conventional marrow harvests.
PMID- 11012152
TI - Hemopoietic progenitor cells in the blood as indicators of the functional status
of the bone marrow after total-body and partial-body irradiation: experiences
from studies in dogs.
AB - The granulocyte-macrophage colony-forming cells (GM-CFC) were studied in the
blood of dogs to evaluate their relationship to the bone marrow GM-CFC under
normal conditions and their involvement in hemopoietic regeneration after
different types of exposure to ionizing radiation. The GM-CFC could be defined as
regular blood elements showing characteristic levels of their concentration in
individual dogs in the range from 20 to 300 cells per ml. In relative terms, the
GM-CFC numbers present in the whole blood of normal dogs were found to be on the
order of 0.1% of the GM-CFC numbers present in the bone marrow. A small fraction
of the GM-CFC population in the bone marrow, i.e., about 1%, can be mobilized
into the peripheral blood within three h by intravenous injection of dextran
sulfate (DS). These cells are characterized by a small size and a low S-phase
fraction similar to the GM-CFC that are normally present in the blood. Total-body
irradiation with single doses of 0.8 Gy and more caused a characteristic pattern
of sequential changes in the blood GM-CFC concentration that were related to the
recovery of the bone marrow GM-CFC population. The blood GM-CFC concentration
showed an extreme depression within the first 15 days, a transient increase from
day 17 to day 35 and remained at subnormal values for several weeks and months.
The regeneration of the GM-CFC population in the bone marrow that could be
mobilized into the blood by DS was similarly delayed as the recovery of the blood
GM-CFC values. In dogs which were kept under continuous radiation exposure (0.019
Gy/day) causing permanent damage to the hemopoietic system, the GM-CFC numbers in
the blood remained permanently depressed. Partial-body irradiation of dogs with a
myeloablative dose (11.7 Gy) given to the anterior part of their body was
followed by sequential changes in the blood GM-CFC concentration specific for
this type of exposure. The pattern of changes was determined by direct radiation
effects, the compensatory responses in the protected bone marrow and the
regeneration events in the irradiated bone marrow. On the other hand, it could be
shown that the repopulation and the restoration of the hemopoietic tissue is
initiated by the seeding of hemopoietic cells (including GM-CFC) from the
protected marrow.
PMID- 11012153
TI - Role of the CD34+ 38- cells in posttransplant hematopoietic recovery.
AB - Using three different statistical tests in parallel, we showed in a preliminary
study that neither mononuclear cells, CD34+ 33+ or 33- cells, nor CD34+ 38+ cells
significantly correlated with engraftment kinetics following autologous blood
cell transplantation (ABCT). We additionally demonstrated here, in a series of
patients suffering from malignant diseases, that the graft content in CD34+ 38-
cells is individually a more sensitive indicator of the earliest, as well as the
latest post-ABCT trilineage hematopoietic recovery than the colony-forming units
granulocyte-macrophage and even the total CD34+ cell content. This suggests that
the CD34+ 38- cell population is itself subdivided into two more subsets, one
being already lineage-committed and responsible for short-term engraftment, the
other containing only very primitive hematopoietic cells responsible for
sustained engraftment. Strong arguments favor the probability that these subsets
correspond to HLA-DR+ and DR cells, respectively. We also defined an optimal
threshold value of 0.05 x 10(6) CD34+ 38- cells/kg of the patient's body weight
(b.w.) above which a rapid and sustained trilineage engraftment safely occurs. In
fact, infusion of lower numbers of cells seems to have a more significant impact
on long-term compared to short-term neutrophil recovery and on platelet kinetics
engraftment. We additionally looked for the eventual influence on engraftment
time of the type of disease, and of post-ABCT administration of hematopoietic
growth factors (HGF). When the type of disease appeared to have no influence on
the engraftment time, posttransplant HGF administration significantly reduced the
time to trilineage engraftment in patients transplanted with < 0.05 x 10(6) CD34+
38- cells, thus justifying it in case of reinfusion of low numbers of CD34+ 38-
cells. On the other hand, the administration of HGF after infusion of more than
0.05 x 10(6) CD34+ 38- cells/kg b.w. did not hasten more, or only very little,
the engraftment time, thus becoming not only unprofitable for the patients but
costly as well.
PMID- 11012154
TI - Hematopoietic progenitor cells in the blood and bone marrow in various
hematologic disorders.
AB - Hematopoietic progenitor cells are present in the blood and the bone marrow.
Changes in the numbers of hematopoietic progenitor cells reflect alteration of
pluripotent stem cells. We discuss such changes in common hematologic diseases
including aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) and
thalassemia. In aplastic anemia, the numbers of burst forming units-erythroid
(BFU-E) and colony-forming units-granulocyte-macrophage (CFU-GM) are much
decreased; the decrease still exists after recovery from therapy. In PNH, the
numbers of progenitor cells are low, even in the presence of marrow
hypercellularity. In thalassemia, the numbers of progenitor cells are much
increased; more pronounced in splenectomized patients.
PMID- 11012155
TI - In vivo expansion of the circulating stem cell pool.
AB - Stem cell trafficking between extravascular marrow sites and circulating blood is
an essential part of the blood stem cell transplantation technology. Recombinant
human G-CSF (rHuG-CSF) is widely used for stem cell peripheralization alone or
together with chemopriming mobilizing early and pluripotent CD34+ cell subsets.
New cytokine/chemokine mobilization regimens are under investigation such as
combined rHuG-CSF and rHu thrombopoietin, rHuG-CSF and interleukin 3, rHuG-CSF
and rHu stem cell factor, rHuG-CSF and Flt-3 ligand, human macrophage
inflammatory protein, interleukin 1, and interleukin 8. Modifying the adherence
of CD34+ cells to extracellular matrix molecules is a new mechanism by which
hematopoietic progenitor cells are released into the circulating blood. Blocking
the alpha4beta1 integrin receptor on CD34+ progenitor cells by using monoclonal
antibodies specific for the heterodimeric complex alpha4beta1 has been shown to
further increase the circulating stem cell concentration when given following
rHuG-CSF priming. The current clinical research is primarily focused on improving
stem cell mobilization efficiency in heavily pretreated and poorly mobilizing
patients, and to decrease adverse effects of cytokine treatment.
PMID- 11012156
TI - Mobilization of blood stem cells.
AB - Deliberately increasing the number of hematopoietic stem and progenitor cells in
the circulation allows faster and more efficient collection of sufficient cells
for transplantation in both the allogeneic and autologous settings. These
mobilized stem cells, when transplanted, provide quicker hematopoietic recovery
for the patient than do nonmobilized blood stem cells or steady-state marrow
derived stem cells. Currently used clinical procedures to produce stem cell
mobilization include administration of G-CSF or GM-CSF, either as single agents
or in combination with myelosuppressive chemotherapy. Some autologous blood stem
cell donors exhibit indifference to currently applied mobilization therapies.
This failure to mobilize has been associated with prior stem cell toxic therapy,
e.g., radiation therapy and chemotherapy, but the association is incomplete. The
observation that occasional normal donors have failed to respond to mobilization
therapy indicates that factors other than stem cell damage could also be
involved. Recently, a murine model has provided evidence that a circulating
factor inhibits mobilization in some settings. Preliminary investigations have
suggested that a circulating factor may inhibit mobilization of human
hematopoietic progenitor cells in some instances. Studies to identify this
factor(s) are underway. The mechanisms of blood stem cell mobilization are still
poorly understood and there continues to be the potential to improve this
process.
PMID- 11012157
TI - Mobilization and transplantation of peripheral blood stem cells.
AB - Two hundred nineteen patients underwent peripheral blood stem cell (PBSC)
transplantation from 1990 to 1997. Stem cells were mobilized with
cyclophosphamide (CY), or with CY plus Taxol or etoposide, followed by cytokines,
and collected when leukocyte counts > or = 1,000/microl, or when CD34+ counts >
or = 20/microl. On average, four to five collections were needed to obtain
sufficient PBSC for engraftment. When CD34+ counts were used, the average number
of collections decreased from 5.4 to 4.2. A discrepancy was noted in the
extraction ratios and number of collections that depended on the optical density
(I/O) setting of the leukapheresis machine. Patients collected at a setting of
100 had higher extraction ratios and required fewer collections (mean = 2.7) than
those collected at 150 (mean = 4.4). This result was unexpected, because the
entire mononuclear cell layer is collected at the higher I/O setting. Further
analysis revealed that a larger volume of red cells was collected at 150 than at
100. These procedures used a small-volume collection chamber, so the chamber was
apparently overloaded by RBC at the higher setting. More rapid recovery of
neutrophil counts and platelet counts was seen in PBSC transplants than in
autologous marrow transplants; moreover, PBSC transplant patients required fewer
RBC and platelet transfusions. Sixteen out of 21 normal donors for allogeneic
PBSC transplants gave adequate collections (> 2.5 x 10(6) CD34+ cells/kg), but
three donors failed to yield > or = 1.5 x 10(6) CD34 cells/kg. This suggests an
inherent difference among certain normal donors that may make PBSC mobilization
difficult.
PMID- 11012158
TI - The role of endothelium in the regulation of hematopoietic stem cell migration.
AB - Mobilization of hematopoietic progenitor cells appears to be a multifactorial
process which is at least partially regulated at the level of bone marrow
microvascular endothelium (BMEC). In order to study the regulation of progenitor
cell migration by endothelium in vitro, methods have been developed to isolate
BMEC from bone marrow aspirates. In addition, immortalized BMEC cell lines have
been generated. Using an in vitro model of migration across bone marrow
endothelium, we demonstrate that only a small number of more mature, committed
progenitors migrate spontaneously. In this model, adhesion molecules of the beta2
integrin family and the corresponding endothelial ligands are involved. The low
spontaneous migratory capacity suggests that, in addition to adhesion molecules
which mediate direct cellular contacts, paracrine cytokines and chemokines may
play a role in progenitor migration across endothelium. Growth-factor-stimulated
hematopoietic cells can produce cytokines which act on endothelial cells (e.g.,
vascular endothelial growth factor, VEGF), modifying their motility, growth,
permeability, and fenestration. Therefore, VEGF might be involved in the
mobilization and homing of hematopoietic progenitor cells. Furthermore,
transendothelial migration of progenitors in vitro is substantially enhanced by
the chemokine stromal-cell-derived factor-1 (SDF-1), which is produced by bone
marrow stromal cells. More primitive progenitors, which do not migrate
spontaneously, also respond to this chemokine. We conclude that transendothelial
progenitor cell migration is regulated by adhesion molecules, paracrine
cytokines, and chemokines. Mobilizing hematopoietic growth factors stimulate
proliferation of hematopoietic cells, which may indirectly result in changes of
the local cytokine and chemokine milieu, adhesion molecule expression, and
eventually the mobilization of hematopoietic progenitor cells.
PMID- 11012159
TI - Rapidly mobilizable stem cells. Do they belong to a special subpopulation?
AB - Some characteristics of rapidly mobilized stem cells as a possible distinct
subset of the murine bone marrow stem cell population are overviewed. Some of the
agents that rapidly mobilize stem cells are toxic and possibly act through
disrupting anchorage to the microenvironment. The mobilization occurring days
after cytostatics and/or colony-stimulating factors (CSF), however, is a
consequence of increased production or differentiation. While stem cells (colony
forming units-spleen; CFU-S) circulating normally in blood have low self-renewal
capacity (SRC), SRC of rapidly mobilized CFU-S is closer to that of bone marrow
stem cells and is similar to that of the late mobilized stem cells. The survival
rate of mice after transplantation of rapidly mobilized stem cells did not differ
from that of bone marrow stem cells. One year after transplantation of rapidly
mobilized stem cells, the SRC value of bone marrow did not differ from those
transplanted with bone marrow cells. Replacement of a rapidly mobilizable stem
cell pool requires 48 h under physiological conditions and a longer time after
damage to hemopoiesis (irradiation, hydroxyurea injection). Possible
physiological mechanisms in the anchorage of stem cells are discussed.
PMID- 11012160
TI - Changes in the cytokine regulation of stem cell self-renewal during ontogeny.
AB - The last 10 years have seen the development of a quantitative assay that is
specific for transplantable totipotent murine hematopoietic cells with durable in
vivo blood-forming ability. Recently, this assay has been successfully adapted to
allow the detection and enumeration of an analogous population of human
hematopoietic stem cells using myelosuppressed immunodeficient (nonobese
diabetic/severe-combined immunodeficiency) mice as recipients. Characterization
of the cells detected by this assay indicates their close relationship in both
mice and humans with cells detected in vitro as long-term culture-initiating
cells (LTC-IC). Culture conditions have now been identified that support a
significant net expansion of these cells from both species. More detailed
analyses of the cytokine requirements for this response indicate that the
viability, mitogenesis and maintenance of LTC-IC function by human CD34+ CD38-
cells can be independently regulated by exogenous factors. Superimposed on this
uncoupling of hematopoietic stem cell "self-renewal" and proliferation control is
a change during ontogeny in the particular cytokines that regulate their
responses. These findings unite stochastic and deterministic models of
hematopoietic stem cell control through the concept of a molecular mechanism that
actively blocks stem cell differentiation and must be maintained when these cells
are stimulated to divide by exposure to certain types and concentrations of
cytokines.
PMID- 11012161
TI - In vivo expansion of hemopoietic stem cells.
AB - Under conditions of steady-state hemopoiesis, a small fraction of immature
hemopoietic cells, including stem cells, circulates in peripheral blood (PB). In
rhesus monkeys, a median number of 1.2 x 10(7)/l CD34+ cells was observed as
opposed to a median number of 1.5 x 10(9)/l in aspirated bone marrow (BM). The
concentration of circulating CD34+ cells is therefore approximately two logs less
than that in BM. Since a 4-kg rhesus monkey has an estimated number of 3 x 10(10)
BM cells and approximately 300 ml of blood, the fraction of CD34+ cells that
circulates can be estimated at approximately 0.4% of the total pool of CD34+
cells. During hemopoietic reconstitution following a cytotoxic insult such as
results from a midlethal dose of TBI, PB CD34+ cell numbers appeared to be
correlated to those of BM, suggesting that PB CD34+ cells may reflect
reconstitution of BM CD34+ cells. Reconstitution of BM immature cells can be
accelerated by treatment with pharmacological doses of growth factors, resulting
in largely expanded immature cell populations within a few weeks after TBI.
Growth factors observed to exert such an effect included, notably,
thrombopoietin. Such an acceleration can be monitored by daily assessment of
circulating CD34+ cells. Expansion of immature circulating cells indicates
expansion of similar cells in the bone marrow rather than growth factor-induced
selective mobilization of immature cells.
PMID- 11012162
TI - Development of natural killer cells from lymphohematopoietic progenitors of
murine fetal liver.
AB - We established a clonal culture system which supports the growth of murine
immature natural killer (NK) cells. When we plated day 14 fetal thymocytes in
methylcellulose media containing interleukin 2 (IL-2), IL-7 and steel factor
(SF), we observed diffuse colonies which could not be classified into known
colony types. Cells in the colonies were blast-like and expressed Thy-1 and CD25
but not lineage-specific markers. Cells in the colonies developed into NK1.1+
cells in fetal thymus organ culture indicating that the colonies consist of
immature NK cells. We then examined the colony-forming ability of fetal liver
cells. The combination of IL-2, IL-7 and SF with or without IL-11 supported
formation of few immature NK cell colonies from purified progenitors.
Interestingly, addition of IL-11 to the culture stimulated formation of mixed
colonies consisting of immature NK cells, B cells, macrophages and/or mast cells.
The clonal origin of the mixed NK cell colonies was confirmed by
micromanipulation of the colony-forming cells. This culture assay should
facilitate the analysis of the pathway and cytokine regulation of NK cell
development.
PMID- 11012163
TI - Ex vivo manipulation of hematopoietic stem and progenitor cells.
AB - Approaches to manipulate peripheral blood progenitor cells (PBPC) ex vivo
currently include the selection of CD34+ cells as a means to purge contaminating
tumor cells from leukapheresis preparations or to provide a homogeneous starting
population for the expansion of hematopoietic progenitor cells as well as the
induction of postprogenitor cells of either the myeloid or megakaryocytic
lineage. The latter cell populations might be used for an additional
transplantation together with PBPC to possibly shorten the period of aplasia. In
addition, ex vivo expansion of CD34+ cells can be used to generate autologous
tumor-antigen-presenting dendritic cells for immunotherapeutic approaches aiming
to treat minimal residual disease following high-dose chemotherapy.
PMID- 11012164
TI - T lymphocytes determine the development of xeno GVHD and of human hemopoiesis in
NOD/SCID mice following human umbilical cord blood transplantation.
AB - Over the past decade the human-immunodeficient mouse chimera has become a well
established in vivo model for studying the human immune system and/or
hemopoiesis. Under certain experimental conditions and depending on the
composition of the human cell graft, the recipient mice may develop a fatal
disease, designated as discordant xenogenic graft-versus-host-disease (GVHD),
which differs in target tissues and histopathology from allogenic GVHD.
Experimental evidence is presented that immunodeficient mice are equally
susceptible to allogenic GVHD as normal immunocompetent mice. Whole human cord
blood and distinct cellular subpopulations from a single cord blood harvest were
transplanted in NOD/severe combined immunodeficient mice and the repopulation of
human cells was monitored over time. Depending on the ratio of lymphocytes to
hemopoietic stem cells, proliferation of human T cells, hemopoiesis or a
combination of the two is observed in widely varying proportions. When the graft
contains a preponderance of lymphocytes, fatal protracted discordant xenogenic
GVHD develops. Mice receiving purified CD34 cells survived up to 207 days in good
health with more than 95% human cells in the bone marrow. In those mice all
lineages (B and T lymphocytes, monocytes, granulocytes, erythrocytes and
thrombocytes) were demonstrated in the bone marrow and peripheral blood.
PMID- 11012165
TI - Amplification of true hemopoietic stem cells: possibilities and limitations.
PMID- 11012167
TI - New vectors for gene therapy.
AB - Retrovirus-based vectors are presently the most efficient gene transfer vehicles
for introducing genes into human hematopoietic stem and progenitor cells.
However, their use for gene therapy is still problematic. A major obstacle is
viral sequences such as the tRNA primer binding site or the dimerization and
encapsidation signals that are not required for the expression of the therapeutic
gene. These sequences can recombine with endogenous and/or exogenous retroviruses
to generate new forms of unpredictable retroviruses. Moreover, these sequences
are the targets for transcriptional repressors which inhibit the expression of
the transduced genes. Therefore we have developed a new generation of retrovirus
vectors which self-delete upon integration. The vectors are based on the natural
life cycle of retroviruses, involving duplication of the terminal control regions
U5 and U3 to generate long terminal repeats, and on the ability of the P1-phage
site-specific recombinase (Cre) to excise any sequences positioned between two
target sequences (loxP). Thus, while inserting a therapy gene into the genome,
the vectors simultaneously excise most proviral sequences that are not required
for gene expression.
PMID- 11012166
TI - Retroviral vectors containing a variant dihydrofolate reductase gene for drug
protection and in vivo selection of hematopoietic cells.
AB - Transfer of drug resistance genes to hematopoietic cells is being studied as a
means to protect against the myelosuppression associated with cancer chemotherapy
and as a strategy for the in vivo selection and amplification of genetically
modified cells. The goal of this study was to test if retroviral-mediated gene
transfer of a dihydrofolate reductase (DHFR) variant (L22Y) could be used for in
vivo selection of transduced myeloid cells and to determine what proportion of
transduced cells was required for protection from myelosuppression. Based on
previous work suggesting that selection with antifolates may also require
inhibition of nucleoside transport mechanisms, mice transplanted with DHFR
transduced bone marrow cells were treated with trimetrexate and the nucleoside
transport inhibitor prodrug nitrobenzylmercaptopurine riboside phosphate. In vivo
selection of transduced myeloid progenitors was seen in the bone marrow and in
circulating mature peripheral blood cells following drug treatment. These results
show that the novel combination of the L22Y-DHFR cDNA, trimetrexate and
nitrobenzylmercaptopurine riboside phosphate can be used to select for transduced
myeloid cells, and that this approach warrants further study in large animal
models. A bicistronic vector containing a human CD24 reporter gene was used to
determine the number of modified cells needed for chemoprotection. Partial
protection from neutropenia was seen when greater than 10% of myeloid cells
expressed the vector, and high levels of protection were obtained when the
proportion exceeded 30%. These results suggest that gene transfer may be useful
for myeloprotection in certain pediatric cancers, but that more efficient gene
transfer will be required to apply this approach to adult cancer patients.
PMID- 11012168
TI - Results of retroviral and adenoviral approaches to cancer gene therapy.
AB - Genetic modification for cancer treatment has involved the introduction of
chemotherapy protection and sensitization genes into normal and tumor cells,
respectively, for the purpose of improving the outcome of conventional approaches
to the treatment of solid tumor neoplasms. This paper will review the use of
multidrug resistance-1 retroviral vectors and cytosine deaminase adenoviral
prodrug activation vectors for this purpose.
PMID- 11012169
TI - Cytokine gene transfer in cancer therapy.
AB - New strategies based on gene transfer technology are employed in cancer therapy.
Cytokines are polypeptides involved in immunity and inflammation, and essentially
control the magnitude of the immune response. Genetically modified tumor cells
releasing various cytokines have been shown to enhance tumor immunogenicity and
to induce the regression of preexisting tumors. In some instances, immunological
memory has been generated to resist the subsequent challenge with unmodified,
parental tumor cells. Cytokine gene transfer into antitumor effector cells, as
well as antigen presenting cells, is also being investigated to augment antitumor
immune responses.
PMID- 11012171
TI - Trombopoietin: from molecule to medicine. Preface.
PMID- 11012170
TI - Cover art: the watercolor drawings of James Homer Wright.
PMID- 11012172
TI - The molecular control of hematopoiesis: progress and problems with gene
manipulation.
AB - The in vitro-based discovery and characterization of hematopoietic regulators
were of great value in identifying many of the agents active in controlling
hematopoiesis. Subsequent in vivo studies have validated most of the information
obtained from the in vitro studies, although the in vitro studies proved to be
somewhat misleading in predicting which agents would exhibit the greatest
quantitative effects in vivo. Establishing more clearly the actual situation in
vivo has required a return to more complex, and often less satisfactory, studies
on genetically-manipulated whole animals. Of the two possible general approaches,
gene inactivation models have proved more informative than transgenic,
overexpression models. Each model has raised multiple questions in need of
further resolution and the deletion studies have also indicated that other
regulators must exist for various lineages, but have yet to be discovered. Of
particular interest is the finding from gene inactivation studies that both G-CSF
and thrombopoietin are necessary for the maintenance of normal numbers of
progenitor cells in multiple lineages, suggesting that each of these lineage
dominant regulators may have broader actions when operating on cells in the stem
cell and progenitor cell compartments.
PMID- 11012173
TI - Native thrombopoietin: structure and function.
AB - Thrombopoietin (TPO), the c-Mpl ligand, is produced constitutively in liver and
other organs, circulates in the bloodstream, and is delivered to bone marrow,
where it stimulates the early development of multiple hematopoietic lineages and
megakaryocytopoiesis. The concentration of TPO in blood is regulated by c-Mpl
mass on platelets and megakaryocytes. In addition to regulation by the number of
TPO molecules, including the possible modulation of TPO mRNA abundance in bone
marrow, megakaryocytopoiesis and platelet production may be regulated as a result
of modulation of TPO activity by proteolytic processing that generates truncated
forms of the molecule. Characterization of TPO partially purified from human
plasma, however, revealed that the full-length molecule was the predominant form
in the blood of both normal individuals and thrombocytopenic patients, although
small amounts of truncated species were detected. Thus, truncation of TPO, at
least that in the circulation examined, does not appear to contribute to the
direct regulation of platelet production in response to increased demand. Given
that native TPO isolated from the plasma of thrombocytopenic animals comprises
truncated forms, the truncation of TPO is likely of physiological importance in
the life history of this molecule.
PMID- 11012174
TI - Peptide agonists of the thrombopoietin receptor.
AB - We have screened a variety of L-amino acid peptide libraries against the
extracellular domain of the human thrombopoietin (HuTPO) receptor, c-Mpl. A large
number of peptide ligands were recovered and categorized into two families.
Peptides from each family compete with the binding of HuTPO and with the binding
of peptides from the other familiy. Representative peptides were synthesized and
found to activate the full-length HuTPO receptor expressed in Ba/F3 cells to
promote proliferation. These peptide families show no apparent homology to the
primary sequence of TPO. We have focused our optimization efforts on one of the
peptides, a linear 14-mer (IEGPTLRQWLAARA) with an IC50 of 2 nM in a competition
binding assay and an EC50 of 400 nM in the proliferation assay. In order to
enhance the potency of the compound, we constructed dimeric peptides by linking
the carboxy-termini of the 14-mers to a lysine branch. These molecules exhibited
slightly higher affinity (0.5 nM) and greatly increased potency (0.1 nM). The
EC50 of the dimeric peptide was equivalent to that of the 332 aa form of
baculovirus-expressed recombinant HuTPO. As previously shown for the
erythropoietin-mimetic peptides, the TPO-mimetic peptides probably activate the
TPO receptor by binding and inducing receptor dimerization. This supposition is
supported by the observation that covalent dimerization of the peptide enhances
its potency by 4,000-fold over that of the monomer. The peptide dimer is also
active in stimulating in vitro proliferation of progenitors and maturation of
megakaryocytes from human bone marrow, and in promoting an increase in platelet
count when administered to normal mice.
PMID- 11012175
TI - IL-3 does not contribute to platelet production in c-Mpl-deficient mice.
AB - Thrombopoietin is a lineage-dominant cytokine involved primarily in the control
of platelet production. The physiological importance of thrombopoietin (TPO) in
the regulation of megakaryocyte and platelet production was demonstrated by the
production of mice deficient in TPO or its receptor, c-Mpl. Even though these
mice are profoundly thrombocytopenic they maintain a basal level of approximately
10% of the normal count of fully functional platelets. These platelets prevent
any abnormal bleeding episodes and highlight the potential importance of other
factors in the control of platelet production. Among the factors with in vitro
megakaryocytopoietic activity, the most potent is undoubtedly interleukin 3 (IL
3). To analyze the contribution of IL-3 to platelet formation in the absence of
TPO, we have generated mice deficient in both c-Mpl and IL-3Ralpha by taking
advantage of a natural mutation present in this gene in the A/J mouse.
Surprisingly, these double knockout mice did not show any further reduction in
their platelet or megakaryocyte counts when compared with c-Mpl-deficient mice.
Similarly, progenitors from other lineages that are also reduced in c-Mpl
deficient mice are not further affected by the absence of a functional IL-3Ralpha
gene. These results demonstrate that IL-3 alone is not responsible for the
production of a basal level of normal platelets in the absence of thrombopoietin
signaling.
PMID- 11012176
TI - Compared effects of Mpl ligand and other cytokines on human MK differentiation.
AB - The discovery of the Mpl ligand (Mpl-L), also called thrombopoietin (TPO), has
facilitated in vitro investigation of human megakaryocytopoiesis. By confocal
microscopy, endomitosis appeared as abortive mitosis skipping late stages of
mitosis. No telophase and cytokinesis were observed. A spherical multipolar
spindle which limits chromatid segregation was observed. The nuclear envelope
subsequently reformed isolating all chromatids in a single nucleus. Platelet
shedding was ultrastructurally studied. Platelet release occurred after formation
of long cytoplasmic extensions (proplatelet formation), constriction areas
delineating platelet territories. Heterogeneity in platelet size may be
determined by the length of these extensions. Pegylated-recombinant human
megakaryocyte growth and development factor, a truncated form of Mpl-L, was the
most efficient cytokine to produce proplatelet-bearing megakaryocytes (MKs) and
platelets in vitro. However, functional platelets with a normal ultrastructure
could be produced in the presence of a combination of other cytokines. Finally,
we investigated whether the induction of MK differentiation by the MS-5 stromal
cell lines is due to Mpl-L. MS-5 cells synthesized Mpl-L transcripts and a
biologically active protein. When human CD34+ cells were grown in contact or
noncontact cultures with MS-5 cells, MK differentiation was observed. Soluble Mpl
receptor (sMpl-Fc) addition inhibited MK growth, suggesting that the MK-promoting
activity was due to Mpl-L production. Marrow stromal cell lines derived from TPO
/- mice were also able to sustain MK growth. Despite the absence of any
production of Mpl-L, the sMpl-Fc continued to inhibit MK differentiation. This
result suggests that the sMpl has a direct inhibitory effect and may explain the
divergent results in the literature concerning the precise role of Mpl-L on the
MK terminal differentiation.
PMID- 11012177
TI - The role of IL-II in hematopoiesis as revealed by a targeted mutation of its
receptor.
AB - Interleukin 11 (IL-11) is a pleiotropic growth factor with several actions in
common with members of the IL-6 family. IL-11 utilizes a specific receptor chain
encoded by two genes, IL-11Ra, which is expressed in hematopoietic and other
tissues and, IL-11Ra2, which has a restricted pattern of expression. The actions
of IL-11 in the hematopoietic compartment include support of multilineage and
committed progenitors contributing to myeloid, erythroid, megakaryocyte, and
lymphoid lineages. IL-11 demonstrates a prominent thrombopoietic activity which
is being evaluated in clinical trials. In contrast to the multiple in vitro and
in vivo effects of IL-11, mice with a targeted mutation of the IL-11Ra gene (IL
11Ra-/-) did not exhibit an overt hematological phenotype. Generation of a null
phenotype was confirmed by independent assays. The numbers of progenitor cells of
various lineages as well as their terminally differentiated progeny were
undisturbed in the IL-11Ra-/- mice. In addition, the mutant mice were able to
respond appropriately to increased demand in situations of hematopoietic stress.
This study has highlighted the growth factor redundancy operative in the
hematopoietic compartment, and in addition, has served to identify a critical
action of IL-11 in nonhematopoietic organs.
PMID- 11012178
TI - Use of the zebrafish (Danio rerio) to define hematopoiesis.
AB - Hematopoiesis in the vertebrate is characterized by the induction of ventral
mesoderm to form hematopoietic stem cells and the eventual differentiation of
these progenitors to form the peripheral blood lineages. Several genes have been
implicated in the differentiation and development of hematopoietic and vascular
progenitor cells, yet our understanding of the discrete steps involved in the
induction of these cells from the ventral mesoderm is still incomplete. One
method of delineating these processes is based on the use of lower vertebrates.
The zebrafish (Danio rerio) is an especially robust vertebrate system for both
isolating and characterizing genes involved in these processes. Hematopoietic
mutants have been generated with defects in many of the steps of both the
primitive and definitive hematopoietic programs. Cloning of the genes that
underlie these mutations should yield valuable details of hematopoiesis and may
have therapeutic implications for bone marrow transplantation and stem cell gene
therapy.
PMID- 11012179
TI - Transcription factor GATA-1 in megakaryocyte development.
AB - The transcription factor GATA-1 is specifically expressed in hematopoietic
lineages. Prior gene knockout experiments established an essential role for GATA
1 in red blood cell production, but could not provide direct evidence with
respect to a requirement in megakaryopoiesis. We summarize here recent lineage
selective gene targeting in mice that establishes critical functions for GATA-1
in controlling megakaryocyte growth and maturation, and platelet production. GATA
1 megakaryocytes are delayed in their cellular maturation, exhibit marked
hyperproliferation and generate fewer than normal, yet enlarged, platelets in
vivo. Thus GATA-1 is a central regulator in both the erythroid and megakaryocytic
lineages.
PMID- 11012180
TI - Analysis of hematopoietic stem cell reprogramming with toxigenicity.
AB - The molecular mechanisms by which a stem cell is committed to individual lineage
are largely unknown. Two different models, though not mutually exclusive, are
currently debated. The first describes the temporal and hierarchical coordination
of lineage-specific transcriptional programs. The second suggests that
multilineage genes are expressed in a self-renewing and undifferentiated cell
prior to lineage commitment. To challenge these two models in in vivo-appropriate
conditions, the expression of an exogenous toxigene was used to create transgenic
animals in which an inducible, reversible cell knock-out at a specific stage of
differentiation could be achieved. Both additional transgenesis using the
megakaryocyte specific alphaIIb promoter and targeted transgenesis were used to
express the herpes virus thymidine kinase (tk) gene in the megakaryocytic
lineage. When the tk gene was targeted to the locus of the megakaryocyte-specific
alphaIIb gene, a typical Glanzman thrombasthenic syndrome was created. Despite
this bleeding disorder, the lack of expression of the alphaIIb gene did not
affect the development of the mice. In both transgenic and targeted animals, all
progenitor cells were sensitive to the effect of the gancyclovir (GCV), both in
vivo and ex vivo. Long-term bone marrow cell cultures on stromal layers indicated
that most of the very early progenitor cells expressed the enzyme. All the
results obtained with this inducible toxic phenotype indicated that genetic
programs that are in control of the expression of lineage-specific genes are
operative in a totipotent stem cell prior to lineage commitment and strongly
support the concept that stem cells express a multilineage transcriptome.
PMID- 11012181
TI - Cellular and molecular biology of megakaryocyte differentiation in the absence of
lineage-restricted transcription factors.
AB - Targeted gene disruption of two distinct lineage-restricted hematopoietic
transcription factors has provided useful insights into the transcriptional
control of platelet production. Absence of either the basic leucine-zipper
protein NF-E2 or of the zinc-finger protein GATA-1 in vivo results in severe
thrombocytopenia secondary to distinct patterns of arrested megakaryocyte
cytoplasmic maturation; in addition, megakaryocyte-selective loss of GATA-1
expression leads to dysregulated proliferation of progenitor cells. The
ultrastructure of the defective megakaryocytes suggests that absence of the
respective transcription factors impairs biogenesis of platelet-specific granules
and proper development and organization of demarcation membranes. In particular,
transcriptional targets of NF-E2 may be implicated in the very final stages of
megakaryocyte differentiation, which involve the organization and release of
platelets. Preliminary characterization of genes that are downregulated in NF-E2
/- megakaryocytes is in progress and is likely to lead to mechanistic insights
into thrombocytopoiesis.
PMID- 11012182
TI - Cyclin D3 and megakaryocyte development: exploration of a transgenic phenotype.
AB - The roles of cell cycle regulatory proteins in megakaryocyte development are
poorly understood. We have previously demonstrated that cyclin D3 is expressed in
megakaryocytes and is induced upon treatment with Mpl ligand. Transgenic mice in
which cyclin D3 is overexpressed in the megakaryocytic lineage show features
similar to in vivo Mpl ligand treatment, including increased megakaryocyte number
and ploidy. Terminal maturation and platelet production are not enhanced,
however, and transgenic megakaryocytes show a defect in demarcation membrane
development. We have examined expression of the transcription factor nuclear
factor (NF)-E2, known to be involved in cytoplasmic maturation and platelet
fragmentation, in these transgenic mice and controls treated with Mpl ligand. Our
findings demonstrate marked induction of NF-E2 mRNA in control megakaryocytes in
response to Mpl ligand, but no NF-E2 increase in transgenic cells, potentially
explaining the lack of platelet increase in these transgenic mice. Transgenic
megakaryocytes treated with Mpl ligand display a limited increase in NF-E2. In
response to literature reports of Mpl ligand-induced transient increases in
p21Cip1/WAF1 mRNA in polyploidizing megakaryocytic cell lines, we have examined
p21 transcript levels in both normal and transgenic megakaryocytes. In normal
mouse spleen, only a small percentage of megakaryocytes express detectable levels
of p21 mRNA, with the majority of these cells expressing at high intensity. p21
levels are not affected by treatment with Mpl ligand, while the frequency of
expressing cells increases transiently. Transgenic megakaryocytes exposed to Mpl
ligand also show an increased frequency of p21-positive cells, and stimulation
with Mpl ligand resulted in a further increase in this frequency. The nature of
this effect will require further investigation.
PMID- 11012184
TI - The effect of MGDF on platelet function and thrombosis in animal models.
AB - Recombinant human megakaryocyte growth and development factor (rHuMGDF) is a
recombinant form of the endogenous c-mpl ligand, thrombopoietin (TPO). rHuMGDF
(and c-mpl ligands in general) can produce a measurable sensitization of
platelets to known platelet agonists. Our laboratory has observed this
sensitization in vitro in both platelet-rich plasma and whole blood and ex vivo
in platelets from animals receiving rHuMGDF. Concurrently, clear increases in the
tyrosine phosphorylation of Jak2 and c-mpl receptor can be observed both in vitro
and ex vivo. To assess the in vivo prothrombotic potential of rHuMGDF, a rabbit
carotid artery model of cyclic flow reduction (CFR) was used. Intravenous
administration of platelet-sensitizing dosages of rHuMGDF had no effect on the
CFR pattern, whereas control experiments demonstrated that the CFR pattern can be
modulated by both platelet sensitizing (epinephrine) and antithrombotic (aspirin
and ketanserin) agents. We conclude that thrombopoiesis can be observed at
dosages that do not sensitize platelets, and further, that platelet-sensitizing
dosages of rHuMGDF do not necessarily enhance platelet-dependent thrombosis in
this model.
PMID- 11012183
TI - Effects of Mpl ligands on platelet production and function in nonhuman primates.
AB - Endogenous thrombopoietin (TPO) stimulates platelet production in nonhuman
primates dose-dependentbyinducing megakaryocyte development from early marrow
hematopoietic progenitors and subsequent proliferation and endoreduplication.
Recombinant human TPO, nonpegylated or pegylated recombinant human megakaryocyte
growth and development factor produce log-linear responses in peak peripheral
platelet counts (or peripheral platelet mass turnover), platelet TPO receptor
density, and marrow megakaryocyte volume, ploidy, number and mass. Mpl ligand
therapy sustains normal peripheral platelet concentrations following
myelosuppressive chemotherapy in baboons and corrects peripheral platelet counts
in HIV-infected chimpanzees with severe thrombocytopenia. Whereas Mpl ligands do
not directly induce platelet aggregation in vitro, they enhance aggregatory
responsiveness of platelets to physiologic agonists both in vitro and transiently
ex vivo following treatment with Mpl ligands. However, platelet recruitment into
forming thrombus is not augmented by these agents when evaluated in quantitative
rabbit or baboon models of platelet-dependent thrombus formation, except for the
direct effect of platelet concentration per se. These findings indicate that
appropriate dosing of these agents prevents thrombocytopenia without increasing
the risk of platelet-dependent thrombo-occlusive complications.
PMID- 11012185
TI - The efficacy of recombinant TPO in murine And nonhuman primate models for
myelosuppression and stem cell transplantation.
AB - Radiation-induced pancytopenia proved to be a suitable model system in mice and
rhesus monkeys to study thrombopoietin (TPO) target cell range and efficacy. TPO
was highly effective in rhesus monkeys exposed to the midlethal dose of 5-Gy (300
kV x-rays) TBI, a model in which it alleviated thrombocytopenia, promoted red
cell reconstitution, accelerated reconstitution of immature CD34+ bone marrow
(BM) cells and potentiated the response to growth factors such as GM-CSF and G
CSF. The accelerated reconstitution of BM CD34+ cells appeared to be reflected by
a similar rise in peripheral blood CD34+ cells, both being augmented by
concomitant GM-CSF. However, TPO was ineffective following transplantation of
limited numbers of autologous BM or highly purified stem cells in monkeys
conditioned with 8-Gy TBI. In the 5-Gy model, a single dose of TPO 24 h after TBI
was effective in preventing thrombocytopenia and was augmented by GM-CSF. The
strong erythropoietic stimulation may result in iron depletion and TPO treatment
should be accompanied by monitoring of iron status. In mice, similar observations
were made and the importance of dose and dose schedule for stimulation of
multilineage repopulating cells versus the lineage-dominant thrombopoietic
response studied in detail.
PMID- 11012186
TI - The combined administration of daniplestim and Mpl ligand augments the
hematopoietic reconstitution observed with single cytokine administration in a
nonhuman primate model of myelosuppression.
AB - This study evaluated the ability of daniplestim, a high affinity interleukin 3
receptor agonist, to enhance the hematopoietic response of Mpl ligand (Mpl-L)
administration in nonhuman primates following severe, radiation-induced
myelosuppression. Rhesus monkeys were total body x-irradiated (TBI) to 600 cGy,
midline tissue dose. Beginning on day 1 post-TBI, animals were s.c. administered
daniplestim (100 microg/kg bid; n = 4), Mpl-L (10 microg/kg qd; n = 3),
daniplestim (100 microg/kg bid) plus Mpl-L (10 microg/kg qd) (n = 4) or 0.1%
autologous serum (AS) (n = 11) for 18 days. CBCs were monitored for 60 d after
TBI. The duration of thrombocytopenia (platelet count; PLT <20,000/microl) was
significantly decreased by the administration of daniplestim (6.5 d, p = .01),
Mpl-L (3.0 d, p = .003) and the coadministered daniplestim/Mpl-L (1.3 d, p =
.001) compared to controls (10.4 d). As monotherapy Mpl-L but not daniplestim
significantly improved the PLT nadir (21,000/microl, p = .023 and 5,000/microl, p
= .266, respectively) compared to the control (3,000/microl). The combined
administration of daniplestim and Mpl-L significantly improved the PLT nadir
(28,000/microl, p = .007) compared to both the control cohort (3,000/microl) and
the daniplestim only cohort (5,000/microl, p = .043). Recovery of PLT to
preirradiation values occurred earlier in the daniplestim only (d 21) or the
daniplestim/Mpl-L cohorts (d 18) than in the Mpl-L only or control cohorts (d 28,
d 29, respectively). The administration of daniplestim or Mpl-L alone neither
shortened the duration of neutropenia (ANC<500/microl) compared to the controls
(15.8 d, 16.0 d versus 16.2 d, respectively), nor improved the recovery time of
neutrophils to baseline values (d 22, d 25, and d 23, respectively). The ANC
nadir was significantly improved by daniplestim alone but not Mpl-L
administration (76/microl, p = .001 and 50/microl, p = .093, respectively)
compared to the controls (8/microl). Coadministration of daniplestim and Mpl-L
significantly improved the ANC nadir (196/microl, p = .001) compared to either
the AS- or the monotherapy-treated cohorts. Also the duration of neutropenia
observed in the AS-controls (16.2 d) was significantly reduced in the
daniplestim/Mpl-L cohort (10.8 d, p = .002). The combined administration of
daniplestim and Mpl-L significantly improved hematopoietic recovery and further
enhanced the stimulatory effect of cytokine monotherapy, as well as reducing
clinical support requirements after radiation-induced bone marrow
myelosuppression.
PMID- 11012187
TI - Myelofibrosis: experimental models and human studies.
AB - Thrombopoietin (TPO) is the central regulator of megakaryocytopoiesis and
thrombocytopoiesis. Preclinical data and human studies have so far shown that the
recombinant molecule is safe to administer and associated with very little
toxicity. Nevertheless, different experimental animal models have revealed that a
chronic exposure to very high doses of TPO could result in myeloproliferative
syndromes with a spectrum of pathological features in common with human
idiopathic myelofibrosis (PMF). A number of investigators have researched whether
TPO or its receptor Mpl were involved in the pathogenesis of human
myeloproliferative syndromes which are also characterized by a predominant
megakaryocytic involvement, in PMF and primitive essential thrombocythemia. In
both diseases, megakaryocyte (MK) progenitors develop autonomously in serum
deprived cultures. This spontaneous MK development is also observed at limiting
dilution demonstrating that MK escape the normal regulatory controls.
Furthermore, this abnormal MK proliferation and maturation is neither due to an
autocrine stimulation by TPO nor by point mutation or deletion in the coding
region of the c-mpl gene. This paper will review the data that have been reported
to date on the effects of an overexpression of Mpl ligand and related molecules
on the induction of experimental myelofibrosis and highlight recent insights into
the pathogenesis of PMF.
PMID- 11012188
TI - Endogenous TPO (eTPO) levels in health and disease: possible clues for
therapeutic intervention.
AB - The factor which is the primary regulator of megakaryocyte and platelet
production has recently been identified as the ligand for the receptor Mpl. This
discovery has resulted in substantial advances in our understanding of platelet
homeostasis. The access to new experimental reagents has enabled studies of the
endogenous circulating form of this ligand, endogenous thrombopoietin, in normal
individuals and in patients with altered platelet numbers. The relationship of
endogenous TPO in health and disease will be examined with consideration of the
implications for successful therapeutic intervention with exogenous recombinant
Mpl ligands in selected settings.
PMID- 11012189
TI - Defective c-Mpl signaling in the syndrome of thrombocytopenia with absent radii.
AB - Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital defect
with severe hypomegakaryocytic thrombocytopenia and bilateral radial aplasia. To
elucidate a possible relationship between thrombocytopenia in TAR and defects in
the thrombopoietin (TPO)/c-Mpl system, we examined TPO activity in sera from six
patients and in vitro reactivity of the patients' platelets to recombinant human
TPO. We found elevated TPO serum levels in all patients, excluding a TPO
production defect as a pathomechanism for the thrombocytopenia. In contrast to
healthy controls, however, platelets of TAR patients failed to respond to
recombinant TPO as measured by testing TPO synergism to suboptimal concentration
of platelet activators. Most interestingly, TPO-induced tyrosine phosphorylation
of platelet proteins was completely absent (four out of five) or markedly
decreased (one out of five). More detailed investigations of the signal cascades
of c-Mpl demonstrated the absence of Jak2 phosphorylation after TPO stimulation
in a TAR patient's platelets. A defect in the early events of c-Mpl signal
transduction might be the reason for impaired megakaryocytopoiesis in TAR
syndrome.
PMID- 11012190
TI - A novel thrombopoietin signaling defect in polycythemia vera platelets.
AB - The pathogenesis of polycythemia vera (PV), a disease involving a multipotent
hematopoietic progenitor cell, is unknown. Thrombopoietin (TPO) is a newly
characterized hematopoietic growth factor which regulates the production of
multipotent hematopoietic progenitor cells as well as platelets. To evaluate the
possibility that an abnormality in TPO-mediated signal transduction might be
involved in the pathogenesis of PV, we examined TPO-induced protein tyrosine
phosphorylation using platelets as a surrogate model system. Platelets were
isolated from the blood of patients with PV as well as from patients with other
chronic myeloproliferative disorders and control subjects. Impaired TPO-mediated
platelet protein tyrosine phosphorylation was a consistent observation in
patients with PV as well as those with idiopathic myelofibrosis (IMF), in
contrast to patients with essential thrombocytosis, chronic myelogenous leukemia,
secondary erythrocytosis, iron deficiency anemia, hemochromatosis, or normal
volunteers. Thrombin-mediated platelet protein tyrosine phosphorylation was
intact in PV platelets as was expression of the appropriate tyrosine kinases and
their cognate substrates. However, expression of the platelet TPO receptor, Mpl,
as determined by immunoblotting, chemical crosslinking or flow cytometry was
markedly reduced or absent in 34 of 34 PV patients and also in 13 of 14 IMF
patients. Impaired TPO-induced protein tyrosine phosphorylation in PV and IMF
platelets was uniformly associated with markedly reduced or absent expression of
Mpl. We conclude that reduced expression of Mpl is a phenotypic characteristic of
platelets from patients with PV and IMF. The abnormality appears to distinguish
PV from other forms of erythrocytosis and may be involved in the platelet
function defect associated with PV.
PMID- 11012191
TI - Overview of the safety and biologic effects of PEG-rHuMGDF in clinical trials.
AB - Completed randomized placebo-controlled phase I/II studies of pegylated
recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) have
demonstrated that this recombinant Mpl ligand has potent and lineage-dominant
effects on megakaryopoiesis and platelet production. Platelets produced after PEG
rHuMGDF administration display normal ultrastructure and functional attributes.
In these early studies, PEG-rHuMGDF accelerated the recovery of baseline platelet
counts after cytotoxic chemotherapy in cancer patients by six to seven days,
indicating the potential for clinical benefit in this setting. PEG-rHuMGDF has
been well-tolerated in clinical trials, with similar adverse events in placebo
and PEG-rHuMGDF populations, and an observed adverse event profile consistent
with the effects of underlying malignancy and chemotherapy. The lack of
inflammatory cytokine effects in the clinic is consistent with results of animal
studies, the narrow tissue distribution of Mpl and the lineage-dominant effect of
PEG-rHuMGDF on megakaryopoiesis. Additional phase I/II studies have commenced in
the fields of cancer chemotherapy and augmentation of platelet donation, and a
phase III study is underway in patients undergoing bone marrow transplantation.
PMID- 11012192
TI - Recombinant human thrombopoietin clinical development.
AB - Patients undergoing anticancer therapy are often at risk for developing severe
and/or prolonged posttreatment thrombocytopenia. This can be associated with
significant bleeding; currently, it is treated with supportive platelet
transfusions. Frequent platelet transfusions can cause alloimmunization which
requires HLA-matched donors and more frequent blood transfusions, and
transmission of both viral and bacterial infections via platelet transfusions
remains a concern. Furthermore, thrombocytopenia can mandate a decrease in the
dose intensity of cytotoxic therapy by causing either delays or dose reductions
in therapy administration. An intervention that reduces the risk or shortens the
duration of severe thrombocytopenia would represent an important medical advance.
Thrombopoietin (TPO), a naturally occurring, glycosylated polypeptide that was
cloned by Genentech in 1994, is capable of inducing differentiation of stem cells
into megakaryocytes and accelerating the maturation of megakaryocytes, thereby
increasing the platelet count. Recombinant human TPO (rHuTPO) is currently
undergoing testing in phase 1 and 2 studies in patients receiving
myelosuppressive or myeloablative therapy. For the purposes of illustration,
preliminary safety and activity data from one ongoing phase 1 myelosuppression
trial (rHuTPO in women with advanced gynecologic malignancies receiving
carboplatin) and one ongoing phase 1 myeloablation trial (rHuTPO for peripheral
blood progenitor cell mobilization prior to myeloablative chemotherapy for high
risk breast cancer) will be presented.
PMID- 11012193
TI - FDA licensure of NEUMEGA to prevent severe chemotherapy-induced thrombocytopenia.
AB - This paper discusses background information and the body of clinical data that
has been accumulated to demonstrate the efficacy and safety of NEUMEGA
(recombinant human interleukin 11) when used to prevent severe chemotherapy
induced thrombocytopenia and reduce the need for platelet transfusions in
patients with nonmyeloid malignancies. NEUMEGA is recommended to be used at a
dose of 50 microg/kg s.c. once daily starting the day after chemotherapy ends
until a platelet count of 50,000 cells/microl is achieved after the expected
nadir.
PMID- 11012194
TI - Early Australian clinical studies with pegylated recombinant human megakaryocyte
growth and development factor.
AB - Pegylated recombinant human megakaryocyte growth and development factor (PEG
rHuMGDF, an Mpl ligand) is a truncated form of native thrombopoietin currently
undergoing clinical development. A series of studies in Australia have examined
the safety and biological activities of PEG-rHuMGDF. Administration of PEG
rHuMGDF causes a dose-dependent increase in platelet count but has no effect on
white cell count or hematocrit. These platelets are morphologically and
functionally normal. When administered following moderately myelosuppressive
chemotherapy, PEG-rHuMGDF significantly enhances platelet recovery, although
scheduling in relation to chemotherapy may be important in optimizing the full
effects. PEG-rHuMGDF mobilizes progenitor cells of multiple hematopoietic
lineages, and alters the kinetics of peripheral blood progenitor cell
mobilization after chemotherapy and filgrastim. PEG-rHuMGDF is well tolerated and
does not cause toxicity similar to that observed with other thrombopoietic
cytokines. Numerous studies are underway to help determine the precise role of
PEG-rHuMGDF in clinical practice.
PMID- 11012195
TI - The use of PEG-rhuMGDF in platelet apheresis.
AB - Platelet transfusions are increasingly being used to treat thrombocytopenic
conditions ranging from aplastic anemia to that caused by cancer chemotherapy.
Although historically whole-blood transfusions were the primary source of
platelets for transfusion, random donor platelet concentrates and single-donor
apheresis platelets are currently the only products used. The use of these
products in the United States varies widely for different medical conditions; for
example, surgical patients receive random donor platelet concentrates much more
commonly than single-donor apheresis products, while the opposite is true for
hematology/oncology patients. The past decade has seen a great change in the type
of platelet product prescribed. Whereas random donor platelet concentrates were
mostly used in the past, over 60% of the platelets transfused are now obtained
from donors by apheresis. A crucial variable in the ability to collect platelets
by apheresis is the donor platelet count. With the recent availability of
thrombopoietin, there has been considerable interest in using this hematopoietic
growth factor to stimulate platelet production in donors. Preliminary studies
with the administration to platelet donors of one of the thrombopoietic growth
factors, PEG-rHuMGDF, have demonstrated a marked increase in the apheresis yield
and no side effects. The PEG-rHuMGDF-mobilized platelets were effective upon
transfusion. Whether stimulation of platelet production in donors with
thrombopoietic growth factors will become a widely accepted method will depend
largely on the safety of this approach for the donor as well as on a number of
lesser issues which concern the recipient and blood center.
PMID- 11012196
TI - The role of c-Mpl ligands in the expansion of cord blood hematopoietic
progenitors.
AB - The major limitations to the widespread use of high-dose chemotherapy or
radiotherapy followed by autologous or allogeneic transplantation are the
scarcity of stem cell donors and the depletion of the autologous stem cell
reservoir. Cord blood is a readily available source of stem cells, which,
however, might be limited in number. For this reason, up to now, cord blood
transplantation has been restricted to children. Therefore, a major goal for
experimental and clinical hematology is the identification of mechanisms and
conditions that support the expansion of transplantable hematopoietic stem cells.
Two systems have been described to identify in vitro these progenitor cell
populations in both mice and humans: A) long-term culture-initiating cells (LTC
IC), so named because of their ability to support the growth of hemopoietic
colonies (colony-forming cell [CFC]) for five to six weeks when cocultured on
stromal layers, and B) the generation of hematopoietic progenitors CFC from
stroma-free liquid cultures for extended periods of time, which is another
indirect evidence for the presence of primitive stem cells. The two systems
detect largely overlapping but not identical cell populations of progenitor
cells; thus, the identification of the growth factor requirements for the
maintenance and amplification of both systems is relevant. The studies presented
here demonstrate that CD34+ cord blood cells can be grown in stroma-free liquid
cultures for extremely prolonged periods of time (up to six months). During such
a period, hemopoietic precursors and committed progenitors belonging to all of
the hematopoietic lineages are continuously and massively generated. Such a
massive expansion is sustained by an increasingly larger expansion of primitive
stem cells (CFU-BI and LTC-IC). The presence of both FL and thrombopoietin (TPO)
was necessary and sufficient to support this phenomenon. The addition of KL +/-
interleukin 6 (IL-6) does not appear to substantially modify the extent of LTC-IC
expansion. FL and TPO appear to be two unique growth factors that preferentially
support the self-renewal of primitive stem cells; the additional presence of KL
and IL-6 seems to enhance the proliferative potential of at least a subpopulation
of daughter stem cells which can undergo at least three differentiation pathways.
PMID- 11012197
TI - Opportunities for the use of thrombopoietic growth factors.
AB - Highly lineage specific thrombopoietic factors are now available which can
produce substantial increments in platelet counts and attenuate the severity of
therapy induced thrombocytopenia in preclinical models and early trials in
patients. These striking findings are not equivalent to proving clinical benefit
to patients, however, and studies are now in progress in a variety of clinical
settings. Methodologic issues which could influence the interpretation of studies
using thrombopoietin to mitigate thrombocytopenia in patients treated for acute
myeloid leukemia and following stem cell transplantation are discussed. Studies
in thrombocytopenic patients with myelodysplasia, aplastic anemia, immune
thrombocytopenic purpura, as well as selected platelet and stem cell donors, are
also of interest. It is unclear, however, whether patients with impaired marrow
function can benefit from further exogenous stimulation, and side effects must be
very carefully monitored in studies with normal donors.
PMID- 11012198
TI - Megakaryocyte and platelet structure in thrombocytopoiesis: the effect of
cytokines.
AB - This paper presents an overview of selected data which the author considers
crucial to an understanding of structure/function relationships of megakaryocytes
(MK) and platelets. The observation that platelet territories form within the MK
cytoplasm and that, therefore, MK and platelet plasma membranes need not be
structurally or antigenically identical is substantiated on the basis of results
obtained with a variety of experiments. While the predominant site of MK
fragmentation is still debated, it is generally accepted that such terms as
"proplatelets," "giant platelets" or "megathrombocytes" refer to MK fragments
consisting of more than one platelet territory. It is suggested that such
fragments be called "compound" platelets to convey a unifying concept. The terms
"young" or "immature" could be reserved for platelets which still contain
ribosomes, rough endoplasmic reticulum or other organelles not usually seen in
circulating platelets. Finally, the structure changes induced by cytokines, such
as interleukin 3 (IL-3), IL-6, IL-11 and thrombopoietin have been illustrated.
PMID- 11012199
TI - Measurements of in vivo megakaryocytopoiesis: studies in nonhuman primates and
patients.
AB - In vivo megakaryocytopoiesis was directly analyzed for megakaryocyte (MK) number
and mass, expression of lineage-specific and myeloid differentiation markers, and
cell maturation as determined by size, granularity and ploidy. Using a rapid
method for multiparameter correlative analysis with three-color flow cytometry
(FCM) and a single-argon-ion-laser analyzer, cell DNA in aspirated marrow was
stained with 7-amino-actinomycin D, and surface membrane receptors were analyzed
with antibodies and cytokines labeled with fluorescein, phycoerythrin and
peridinin chlorophyll protein. MKs expressing glycoprotein (GP) IIb/IIIa were
enumerated in relation to the nucleated erythroid precursors expressing
glycophorin A, and MK diameters were measured by time-of-flight technique. In
human marrow (n = 10) the average MK diameter is 37 microm (range: 21 microm for
2N to 56 microm for 64N cells), volume is 26 x 10(3) fL, and MK number is 10 x
10(6)/kg, giving a total MK mass of 26 x 10(10) fL/kg. The modal ploidy is 16N.
In essential thrombocythemia patients (n = 10) with a mean platelet count of 907
+/- 23 x 10(6)/L, MK number and volume increased twofold with modal ploidy of
32N, and MK mass fourfold the normal value. After reducing the platelet count to
353 +/- 42 x 10(6)/L with anagrelide therapy, MK number and volume decreased with
modal ploidy of 16N, resulting in reduced MK mass by 50%. By contrast, patients
with chronic myelogenous leukemia (n = 3) showed an increase in small MKs with a
modal ploidy of 8N. In non-human primates, treatment with interleukin 6 or GM-CSF
increased MK volume and ploidy with a variable increase in cell number and
platelet counts. Treatment with recombinant human MK growth and development
factor (n = 6, 5 microg/kg for 28 days) increased platelet count fivefold, MK
number fourfold, MK volume twofold and total mass sevenfold. Using three-color
FCM, marrow MKs labeled for GPIIb/IIIa and stained for DNA expressed high levels
of von Willebrand factor with a high resolution of 2N/4N MKs from the total
marrow cells. The expression of myeloid markers including CD36, CD45 and IgG-Fc
gammaRII CDw32 correlated directly with increasing cell maturation, concordant
with the expression of GPIIb/IIIa and GPIb. Conversely, the expression of HLA-DR
declined with maturation. We conclude that pathophysiologic and therapeutic
changes in megakaryocytopoiesis in vivo are readily quantified using FCM
measurements.
PMID- 11012200
TI - Early suppressive effects of chemotherapy on recovery of bone marrow
megakaryocyte precursors: possible relationship to platelet recovery.
AB - This study utilized a recently developed culture and quantitation system to
detect megakaryocyte precursors in CD34+ bone marrow cells from normal donors and
breast cancer patients treated with 5-fluorouracil, leucovorin, adriamycin and
cyclophosphamide (FLAC). Bone marrow was obtained from patients before and then
after their first cycle of FLAC once blood cell counts had recovered. CD34+ cells
were isolated and placed in liquid culture with growth factors to stimulate
proliferation and lineage commitment. Absorbance values from an enzyme-linked
immunosorbent assay were used to quantitate expression of platelet glycoprotein
GPIIb/IIIa. There was an increase in absorbance with increasing numbers of cells
seeded per culture that was associated with an increase in the number of
megakaryocyte lineage cells produced. After 10 days in liquid culture, absorbance
values for expression of GPIIb/IIIa from 2,000 normal donor and pre-chemotherapy
CD34+ marrow cells were > or = 1.0. Absorbance values from cultures of post
chemotherapy CD34+ cells from four patients were similar to values from pre
chemotherapy CD34+ cells. In contrast, absorbance values from cultures of post
chemotherapy CD34+ cells from two other patients were low (absorbance < 0.5). Low
absorbance values for GPIIb/IIIa expression indicate that megakaryocyte
production from those CD34+ cells was reduced. Both of those patients developed
prolonged thrombocytopenia and platelet nadirs of less than 20,000/microl during
FLAC chemotherapy. In contrast, only one out of four patients whose cultures of
post-chemotherapy CD34+ cells had absorbance values > or = 1.0 developed platelet
nadirs less than 20,000/microl. These results suggest that low platelet nadirs
and delayed platelet recovery may be associated with suppressive effects of
chemotherapy on recovery of megakaryocyte precursors.
PMID- 11012201
TI - The regulated expression of a TATA-less, platelet-specific gene, alphaIIb.
AB - The megakaryocyte (MK)-specific integrin, alphaIIb, is the alpha-subunit of the
alphaIIb/beta3 complex found on the surface of platelets. This complex is a
receptor for fibrinogen and other ligands when platelets are activated. Because
the alphaIIb gene is specifically expressed in MKs, this gene was studied as a
potential model for MK-specific gene expression. Previous studies have defined
some of the important regulatory elements in 912 bp of the immediate 5'-flanking
region of this gene. These studies defined several important elements including
two GATA-binding elements and an Ets-binding element. Using a primary rat marrow
expression system, we demonstrated that one of the GATA-binding elements, -454 bp
upstream of the transcriptional start site (GATA454), is critical for expression
of the alphaIIb gene. A potential negative regulatory element was found between
100 and -200 bp upstream of both the rat and human alphaIIb genes. The biological
basis by which this negative regulatory region effects expression is not well
understood. Recent studies have focused on the issue of the molecular basis by
which this TATA-less gene is properly transcribed. We found that a GA-rich region
approximately 14 bp upstream from the transcriptional start site appears to be a
nonconsensus Sp1-binding site that interacts with an Ets-consensus site
approximately 20 bp further upstream. These studies provide further evidence of
the role of interactions between Ets-like proteins and Sp1 in transcriptional
activation when a TATA box is not present in the promoter region of a gene. Based
on the presented studies and previous results, a model is proposed for the
regulation of expression of the alphaIIb gene. In studies looking at more distal
regulatory elements, we have found, using the primary rat marrow expression
system, that 2.9 kb of 5'-flanking alphaIIb sequence has as high a level of
expression as the 912 bp construct. Whether either of these lengths of 5'
flanking region can result in tissue-specific expression in transgenic models is
presently being investigated. In addition, while a published report suggests that
the two genes alphaIIb and beta3 are physically linked within a 250 kb region of
genomic DNA, analysis of yeast artificial chromosome clones and genomic pulsed
field gel electrophoresis analysis are consistent with these two genes not being
tightly linked and being >1 mb apart, suggesting that these two genes do not form
a single, tissue-specific locus.
PMID- 11012202
TI - Preclinical biology of megakaryocyte growth and development factor: a summary.
AB - Since the discovery of the ligand for the cytokine receptor c-Mpl, much has
transpired. The development of this protein has been rapid, and the amount of
information available on the effects of this molecule in vitro and in vivo is
vast. This paper will highlight some of the major studies and observations which
are part of the ongoing pre-clinical development of the megakaryocyte growth and
development factor encoding the erythropoietin-like domain of the c-Mpl ligand. A
summary of in vitro effects on human cells, as well as the key in vivo
observations, are included. This molecule is currently in clinical trials, and
the initial results are promising.
PMID- 11012203
TI - The role of recombinant interleukin 11 in megakaryocytopoiesis.
AB - Recombinant human interleukin 11 (rHuIL-11) is a multifunctional cytokine with
activities on a broad range of hematopoietic cells including primitive stem cells
and mature progenitor cells. Analysis of rHuIL-11 in vitro has revealed that its
hematopoietic activities are predominantly a result of synergistic interactions
with other early-acting factors such as IL-3 and Steel factor. Studies indicate
that rHuIL-11 acts directly on purified stem and progenitor cell populations and
can support the growth of colony forming units-megakaryocyte in these cultures.
In normal animals, rHuIL-11 has a potent effect on cells of the megakaryocyte
(MK) lineage. Administration of rHuIL-11 results in a two- to threefold increase
in circulating platelets, stimulation of bone marrow (BM) and spleen progenitor
numbers, and enhanced MK maturation as measured by a shift to higher ploidy
values. rHuIL-11 administration in preclinical models of myelosuppression induced
by chemotherapy and/or irradiation has shown a reproducible acceleration of
platelet recovery and, in some models, enhanced neutrophil and red blood cell
recovery. rHuIL-11 has been tested in a non-human primate myelosuppression model
using carboplatin. Administration of rHuIL-11 following carboplatin treatment was
found to eliminate the period of severe thrombocytopenia (<20,000 platelets/ml)
and enhance the recovery of platelets to normal levels (>100,000/ml). Recently,
human clinical trials conducted with rHuIL-11 in patients treated with
chemotherapy have demonstrated its potent thrombopoietic activity, including
improved platelet nadirs, enhanced platelet recovery and a significant decrease
in the number of patients who require platelet transfusions. Combined with the
preclinical results, these studies confirm that this cytokine will be an
effective agent in the treatment of myelosuppression and thrombocytopenia
associated with cancer chemotherapy and BM transplantation.
PMID- 11012204
TI - Characterization, molecular cloning and expression of megakaryocyte potentiating
factor.
AB - We examined whether the conditioned media of 64 kinds of cell lines, which have
been maintained by a protein-free culture system, could produce megakaryocyte
potentiating (Meg-POT) activity. In these cell lines, HPC-Y5, established from
human pancreatic cancer, was shown to have the highest level of activity. The
megakaryocyte potentiating factor (MPF) was purified from its conditioned medium
by a combination of ion-exchange chromatography, gel filtration and reversed
phase HPLC. The purified MPF showed Meg-POT activity almost equal to human (Hu)
interleukin 6 (IL-6) in the presence of murine IL-3 in a colony-forming assay
with mouse bone marrow cells. The molecular weight of MPF was estimated to be 33
kDa by SDS-PAGE. Glycopeptidase F digestion and amino sugar analysis of the
factor demonstrated that MPF is a glycoprotein carrying at least one N-linked
sugar chain. The N-terminal amino acid sequence of MPF was determined to be Leu
Ala-Gly-Glu-Thr-Gly-Gln-Glu-Ala-Ala-Pro-Leu-Asp-Gly-Val-Leu-Ala-Asn. The same or
homologous amino acid sequence has not been found in known proteins,
demonstrating that MPF may be a novel cytokine which has Meg-POT activity. Then,
we isolated HuMPF cDNA from an HPC-Y5 cDNA library using polymerase chain
reaction and plaque hybridization methods. The HuMPF cDNA encodes a polypeptide
consisting of 622 amino acids, including a signal peptide of 33 amino acids, and
with a deduced molecular weight of 68 kDa, although HPC-Y5 cells secrete a 33 kDa
form of HuMPF. HuMPF cDNA does not show any significant homology with other known
sequences. The cDNA was expressed in COS-7 and Chinese hamster ovary (CHO) cells,
and Meg-POT activity was detected in their culture supernatant. The COS-7 cells
secreted only a 33 kDa recombinant (r)HuMPF, however, an additional 30 kDa form
was detected in the culture medium of CHO cells. The 33 kDa rHuMPF from CHO cells
showed Meg-POT activity, but not the purified 30 kDa rHuMPF. The difference in
structure and activity between the 33 and 30 kDa forms of HuMPF was ascribed to
the existence in the 33 kDa form of the C-terminal 25 amino acid residues. The
expression of MPF mRNA was examined by Northern blot analysis using labeled MPF
cDNA as a probe. MPF mRNA was detected in HPC-Y5 cells, with an approximate
molecular size of 2.4 kb. We also examined the expression of the MPF gene in
various human tissues, and the 2.4 kb band was detected only in lung. Then, the
immunohistocytochemical analysis and in situ hybridization revealed that MPF
producing cells were identified as lung macrophages. MPF may exhibit other
biological activities such as regeneration of the lung tissues.
PMID- 11012205
TI - Hierarchical structure of human megakaryocyte progenitor cells.
AB - Megakaryocytopoiesis is a complex biological process involving a series of
cellular events that begins with the pluripotent hematopoietic stem cell and
ultimately results in the biogenesis of platelets. A hierarchy of megakaryocyte
(MK) progenitor cells has been previously defined based upon studies of in vitro
megakaryocytopoiesis. Ontogeny-related changes in MK progenitor cells were
analyzed in order to further define this cellular hierarchy. Unifocal colony
forming unit-megakaryocyte (CFU-MK)-derived colonies cloned from fetal bone
marrow (FBM) formed after fewer days of in vitro culture and were 2.6-fold larger
than those colonies cloned from adult bone marrow (ABM). The frequency of CFU-MK
derived colonies cloned from ABM was significantly greater. MK colonies, however,
cloned from FBM morphologically consisted of both pure MK colonies and mixed
colonies containing MKs, in which a core of CD41- cells were surrounded by CD41+
MKs. Large colonies resembling the primitive BFU-MK also were assayed from both
FBM and ABM. These BFU-MK-derived colonies appeared after fewer days of
incubation when FBM was assayed, compared to ABM, but at a significantly lower
frequency. In addition, large unifocal MK colonies consisting of >300 cells (300
1000) appeared from cells cloned from fetal, but not adult, marrow. This type of
colony represents a unique type of MK progenitor cell, termed the high
proliferative-potential cell-MK. Such colonies represent the progeny of the most
primitive human MK progenitor cell identified to date. We also attempted to
investigate the process of commitment of stem cells to the MK lineage. We
explored the actions of thrombopoietin (TPO) on primitive hematopoietic cells in
order to gain an understanding of stem cell commitment. CD34+ Thy-1+ Lin- marrow
cells, which are enriched for pluripotent hematopoietic stem cells, were shown to
express c-Mpl by the polymerase chain reaction. In addition, TPO alone was
capable of inducing CD34+ Thy-1+ Lin- cells after two to three weeks to produce
progeny composed entirely of MKs. These studies indicate that TPO has a profound
effect on hematopoietic stem cells, and that the hierarchy of MK progenitor cells
begins with the pluripotent hematopoietic stem cell.
PMID- 11012206
TI - Cloning and functional analysis of erythropoietin-, interleukin-3- and
thrombopoietin-inducible genes.
AB - The receptor for thrombopoietin (TPO) is a member of the cytokine receptor
superfamily. This superfamily also includes the receptors for erythropoietin
(EPO), interleukin 3 (IL-3), GM-CSF and several other cytokines. Stimulation of
cytokine receptors with their cognate ligands results in the activation of
multiple signal transduction pathways and ultimately in the induction of new
genes. The cloning of these specific genes provides one approach for analyzing
cytokine-specific responses. In the current study, we have designed a strategy
for isolating inducible genes. While the strategy has been used to identify EPO
specific and IL-3-specific inducible genes, the strategy can be extended to clone
TPO-inducible genes.
PMID- 11012207
TI - The physiology of platelet production.
AB - The production of platelets from the bone marrow megakaryocytes is a well
regulated process. Nearly 100 years ago, James Homer Wright described how
platelets formed from megakaryocytes and entered the circulation. Subsequent
clinical and animal studies have enumerated a number of principles of platelet
physiology: the platelet count is constant in any one individual but varies
greatly between individuals; an inverse relationship exists between the platelet
count and platelet size; the body conserves the mass, not the number, of
platelets; and megakaryocyte number, size and ploidy vary in response to changing
demands for platelets. With the discovery of thrombopoietin (TPO), a number of
additional physiological principles have emerged: TPO takes 24 h to rise
maximally and has a maximal half-life of 45 min; TPO levels are inversely and
exponentially proportional to the platelet mass; platelets bind and clear TPO
from the circulation; and hepatic TPO product on is not altered by changes in the
platelet mass. Using these principles, a model for the regulation of platelet
production by TPO has been proposed in which the constitutive hepatic TPO
produced is removed from the circulation by the platelet mass. Changes in the
platelet mass or its ability to clear TPO produce changes in TPO levels resulting
in an altered platelet production rate. Using this model, a number of
pathological disorders of platelet production, such as essential thrombocythemia
and idiopathic thrombocytopenic purpura, are analyzed.
PMID- 11012208
TI - Biological roles for the second domain of thrombopoietin.
AB - Thrombopoietin (TPO) has been isolated from the plasma of animals in several
laboratories as several molecular species which vary in molecular weight from 19
kDa to 35 kDa. Upon biochemical analyses, all of these forms appear to represent
proteolytic fragments of TPO which share the same amino-terminal sequences and
are therefore truncated at their C-terminal ends. Intact recombinant TPO produced
in cell culture is a 70 kDa glycoprotein which contains the full polypeptide
backbone encoded by the cDNA sequence. A series of deliberate TPO truncations
have been constructed by the introduction of stop codons into the cDNA at various
positions. The proteins encoded by the truncated cDNAs have been purified to
homogeniety for the purpose of detailed biological and biochemical comparisons of
such C-terminally truncated TPO proteins with the full-length intact TPO. These
comparisons serve to illuminate the possible biological role(s) of the C-terminal
domain, which is so far unique in the family of hematopoietic cytokines. The C
terminal domain appears to regulate the specific activity of TPO, to regulate its
circulating half-life, and to promote efficient biosynthesis and secretion of the
protein.
PMID- 11012209
TI - Do the preclinical effects of thrombopoietin correlate with its in vitro
properties?
AB - In the short time since its cloning, much has been learned of the in vitro
properties of thrombopoietin (TPO). In addition to effects on the differentiation
of megakaryocytes, TPO has also been shown to stimulate the proliferation of
megakaryocytic progenitor cells, colony-forming units-megakaryocytes (CFU-MK), to
act in synergy with interleukin 3 or c-kit ligand and erythropoietin (Epo) to
stimulate the development of early and the generation of late erythroid
progenitor cells, and to affect the rate of entry into the cell cycle and
proliferative capacity of hematopoietic stem cells. An important question posed
by these observations, for both TPO and for hematopoietic research in general, is
whether the in vitro effects of a cytokine are mirrored by its preclinical and
clinical biology. The results of recent studies in mice and nonhuman primates
will be presented which have attempted to address this issue. In normal animals,
TPO increases the numbers of marrow and spleen CFU
granulocyte/erythroid/macrophage/megakaryocyte, CFU-MK, CFU-GM and BFU-E, but its
effects in the peripheral blood are limited to marked increases in the platelet
count. The reason for widespread progenitor cell effects, yet stable leukocyte
and erythrocyte blood counts, is likely the predominant regulatory effects of G
CSF and Epo; in the absence of elevated levels of the lineage-dominant regulator
of each of these cell types, expanded progenitor cell numbers are not translated
into increased peripheral blood counts. However, in states of increased blood
cell demand such as follows myelosuppressive therapy, elevated levels of Epo and
G-CSF allow the effects of TPO on erythropoiesis and myelopoiesis to become
manifest. The administration of TPO to myelosuppressed animals is associated with
not only greatly expanded hematopoietic progenitor cell recovery, but also
improvement in platelet, red cell and leukocyte nadir levels and greatly
accelerated recovery of all three cell lineages. These results indicate that the
panhematopoietic properties of TPO identified by in vitro culture techniques
correlate well with its effects in animals. The results of ongoing clinical
trials should soon establish whether these conclusions can be extended to patient
care.
PMID- 11012210
TI - The role of transcription factor NF-E2 in megakaryocyte maturation and platelet
production.
AB - To determine the in vivo functions of the transcription factor NF-E2, we have
disrupted the gene encoding its hematopoietic-specific p45 subunit in embryonic
stem cells and generated knockout mice. These animals have a surprisingly mild
erythroid cell abnormality but experience lethal hemorrhage as a result of
profound thrombocytopenia. Impaired platelet formation is secondary to a
cytoplasmic maturation arrest within megakaryocytes, characterized by a marked
reduction in granule numbers. Although the proliferative response to recombinant
thrombopoietin is intact, this is not accompanied by correction of the
differentiation defect. Absence of the smaller (p18) subunit of NF-E2 does not
have similar consequences. These findings implicate target genes of the NF-E2
transcription factor in critical aspects of late megakaryocyte maturation and
platelet formation.
PMID- 11012211
TI - Dissection of c-Mpl and thrombopoietin function: studies of knockout mice and
receptor signal transduction.
AB - The physiological roles and mechanisms of action of thrombopoietin (TPO) and its
receptor c-Mpl have been studied through the analysis of mice genetically
deficient in these molecules, as well as through the dissection of signaling
events utilizing chimeric receptors. The evidence clearly demonstrates that the
TPO/c-Mpl system provides dominant control in the regulation of
megakaryocytopoiesis. The signaling mechanisms that underlie this process appear
to be similar to those noted with other members of the hematopoietic cytokine and
cytokine receptor families.
PMID- 11012212
TI - Studies of the c-Mpl thrombopoietin receptor through gene disruption and
activation.
AB - The c-mpl gene encodes a receptor for thrombopoietin (TPO), a cytokine that
potently stimulates megakaryocytopoiesis. To study the mechanisms of c-Mpl
activation, we generated constitutively active receptor mutants. Substitution of
cysteine residues into a dimer interface homology domain of c-Mpl forced ligand
independent homodimerization and constitutive receptor activation. In factor
dependent cells, mutant receptors induced autonomous growth and tumorigenicity.
The receptors were constitutively phosphorylated in these cells, as were signal
transduction molecules implicated in Mpl function. These data suggest that the
normal process of ligand-induced Mpl activation involves receptor
homodimerization and that mutated forms of the cellular mpl gene can contribute
to tumorigenicity. We have also examined the biological role of c-Mpl in mpl
deficient mice generated via homologous recombination in embryonic stem cells.
Homozygous mutant animals were deficient in megakaryocytes and severely
thrombocytopenic. Mature cells from all other hemopoietic lineages were
unaffected. Bone marrow cells from mpl-/- mice were incapable of binding to TPO
or responding to the cytokine in clonogenic assays, and further displayed a
marked deficiency in progenitor cells capable of megakaryocyte colony formation
in response to other stimuli. Moreover, total progenitor numbers were also
deficient and included significant reductions in colony-forming cells of multiple
hemopoietic lineages. Unexpectedly, the numbers of progenitor cells of all
lineages were not perturbed in mid-gestation mpl-/- fetal liver. Our analyses
suggest an indispensable role for c-Mpl in megakaryocyte development and reveal
that the function of TPO and its receptor is not confined solely to activities in
megakaryocytopoiesis.
PMID- 11012213
TI - Physiologic role of TPO in thrombopoiesis.
AB - Recombinant human thrombopoietin (rHuTPO) serves as a megakaryocyte colony
stimulating factor and predominantly acts on GPIIb/IIIa+ rat late megakaryocyte
progenitor cells, colony forming units-megakaryocyte (CFU-MK). The GPIIb/IIIa+
fraction of CFU-MK differentiates into mature megakaryocytes and further into
proplatelets in liquid culture containing rHuTPO. rHuTPO stimulates cultured
megakaryocytes generated from rat GPIIb/IIIa+ CFU-MK to enhance proplatelet
formation and to increase megakaryocyte size. rHuTPO also induces a big size of
megakaryocyte colonies from human cord blood CD34+ cells. rHuTPO does not cause
aggregation of platelets from normal mice and mice made thrombocytotic by
consecutive administration of rHuTPO, but preincubation with rHuTPO enhances
adenosine diphosphate-induced aggregation, suggesting that platelets induced by
rHuTPO administration may have a normal function. Administration of rHuTPO to
normal mice daily for five days causes a dose-dependent thrombocytosis. On the
other hand, rHuTPO induces a significant decrease in hemoglobin concentration and
does not affect white blood cell counts. rHuTPO increases the size and number of
marrow megakaryocytes and the number of marrow CFU-MK, and also influences the
development of other hematopoietic progenitor cells. The effects of rHuTPO on
thrombocytopenia associated with myelosuppression were examined in animal models.
Following treatment with mitomycin C, mice received daily injections of various
doses of rHuTPO. rHuTPO reduced the severity of thrombocytopenia, accelerated the
recovery of platelets and improved neutropenia. Similar therapeutic efficacy was
observed in cynomolgus monkeys treated with nimustine. These results suggest the
clinical usefulness of rHuTPO for the treatment of thrombocytopenia.
PMID- 11012214
TI - Protein characteristics of thrombopoietin.
AB - Thrombopoietin (TPO) was purified from irradiated thrombocytopenic rat plasma. In
the process of purification, some biochemical and biological characteristics were
investigated. Rat plasma TPO was extremely hydrophobic and exhibited multiple
peaks of activity on gel filtration. Both the low and high molecular weight
fractions were separately subjected to further purification. Consequently, a rat
TPO cDNA was cloned based on the amino acid sequences of purified rat plasma TPO.
It revealed that each final purified rat plasma TPO was not a full-length form.
In addition, rat hepatocytes and three rat hepatoma cell lines were found to
produce rat TPO. Each native TPO derived from cultured cells was also partially
purified, and hepatocyte-derived TPOs were shown to be heterogeneous in molecular
weight. To study the structure of TPO, various recombinant TPO molecules were
generated. Two disulfide bonds (Cys7-Cys151 and Cys29-Cys85) located in the N
terminal domain of TPO have an important effect on its biological activity. The
human TPO muteins, sequentially deleted from the C-terminal, were expressed in
COS-1 cells. TPO (1-151) was active, but TPO (1-150), which lacks Cys151, did not
exhibit TPO activity. These findings indicate that the region essential for TPO
activity is the N-terminal domain, which contains two disulfide bonds. Although
the role(s) of the C-terminal domain is not clear at present, the potential N
glycosylation in the C-terminal domain is not directly required for exhibiting
TPO activity.
PMID- 11012215
TI - Gene expression and transcriptional regulation of thrombopoietin.
AB - Thrombopoietin (TPO) is predominantly expressed in the liver among various
tissues that express TPO transcripts. To investigate the transcriptional
regulation of the human TPO gene in the liver, we determined the major
transcription initiation site by means of 5'-RACE and Northern blotting. From
these analyses, we concluded that TPO gene transcription started at various
points, and the transcription initiation sites of the human TPO gene were
localized downstream, close to a point we determined by S1 nuclease mapping. The
human TPO promoter region contains consensus sequences of GATA, Evi-1, and Ets
binding sites. We used the hepatocellular carcinoma cell line, HepG2, that
expresses TPO mRNA to analyze its promoter activity by transfecting various
reporter plasmids containing a sequentially 5'-deleted human TPO promoter.
Although GATA binding factors increased the promoter activity, their effect was
independent of the GATA binding consensus sequence. On the other hand, Evi-1 did
not affect transcription. Moreover, we defined the core promoter region, in which
an Ets binding consensus sequence was located. The deletion or mutation of the
Ets binding site resulted in a loss of the promoter activity. These results
suggested that TPO is regulated by the Ets family of transcription factors.
PMID- 11012217
TI - Megakaryocytopoiesis in vitro: from the stem cells' perspective.
AB - Megakaryocytopoiesis is a complex network regulated by different megakaryocyte
(MK)-stimulating factors (i.e., thrombopoietin [TPO], stem cell factor [SCF],
interleukin 3 [IL-3], IL-6, IL-11 and GM-CSF). Although all of these factors can
affect human and murine megakaryocytopoiesis at different levels of MK
development, the effect on very primitive hematopoietic stem cells (HSC) is not
well understood. We have further characterized the in vitro biological activity
of recombinant murine TPO, SCF and IL-3 on the maturation and proliferation of MK
progenitors from different murine primitive hematopoietic cells in a fibrin clot
system under serum-free conditions. Neither TPO nor SCF alone induced MK colony
formation (CFU-MK) from Lin- Sca+ cells. However, isolated large and mature MKs
were observed in the presence of TPO. In contrast, IL-3 exerted a potent effect
on CFU-MK formation from Lin- Sca+ cells. On this population of HSC, a
significant increase of large MK colonies with mature MK were obtained under
those conditions in which TPO was combined with IL-3 or SCF plus IL-3. Similar
results were obtained with murine bone marrow cells enriched by primitive
progenitors from day 3 post-5-fluorouracil treated mice (5-FUBMC). In contrast,
TPO-sensitive precursors were detected in fetal liver cells (FLC). These cells
differentiate and proliferate to MK progenitors in the presence of TPO. A
significant increase in the number of CFU-MK was induced when TPO was combined
with either IL-3 or SCF. On these populations of primitive hematopoietic
progenitors, IL-3 induced both the proliferation and differentiation of MK
progenitors. Because erythropoietin and TPO share similarities between their
molecules and their receptors, we studied whether these growth factors may
modulate megakaryocytopoiesis from FLC. Flow cytometry analysis of FLC expressing
erythroid markers demonstrated that these cells expressed c-Mpl receptor. In our
in vitro studies, although EPO by itself did not induce MK colonies from FLC, it
enhanced the proliferative activity of TPO. High ploidy and proplatelet-shedding
MK were observed in Lin- Sca+ cells, 5-FUBMC and FLC stimulated with TPO alone or
in combination with other MK-stimulating factors. Based on these observations, we
propose that TPO, IL-3 and SCF constitute early MK-acting factors with
differential proliferative and differentiative activities on murine stem cells.
TPO by itself does not appear to be involved in the proliferation of MK
progenitors from bone marrow HSC. TPO appears to induce in these cells the
commitment toward MK differentiation. However, this growth factor may enhance the
proliferative activity of IL-3. IL-3 is an early MK-stimulating factor able to
induce in vitro the proliferation and differentiation of MK progenitors from HSC.
PMID- 11012216
TI - Cytokine-induced alteration of platelet and hemostatic function.
AB - A number of nonplatelet-specific cytokines that augment platelet recovery
following chemo/radiotherapy have been described. The members of the interleukin
6 (IL-6) family have properties that influence the hematopoietic system beyond
their modest thrombocytopoietic effects. Studies performed in a canine model with
IL-6 have shown that this factor augments plasma fibrinogen and von Willebrand
factor (vWf) concentrations and decreases the level of free protein S. IL-6
appears to decrease the bleeding time in thrombocytopenic dogs, although this
effect does not seem to be due to a direct influence of the factor on endothelial
vWf or tissue factor production. The factor does not directly alter platelet
function in vitro, but when administered to dogs, it increases the sensitivity of
the platelets to activation by thrombin. Normal platelets injected into IL-6
treated dogs, and platelets from IL-6-treated dogs injected into normal animals,
survive normally. Following injection of either IL-6 or the more specific
thrombocytopoietic cytokine thrombopoietin (TPO), IL-6 increases platelet
responsiveness to thrombin-induced activation to a greater extent than does TPO.
The data show that IL-6 has certain properties that might be construed as
prohemostatic, and these properties may prove to be useful clinically.
PMID- 11012218
TI - Thrombopoietin, a direct stimulator of viability and multilineage growth of
primitive bone marrow progenitor cells.
AB - Thrombopoietin (TPO), the ligand for c-mpl, has recently been demonstrated to be
the primary regulator of megakaryocytopoiesis and platelet production. In
addition, several studies have demonstrated that c-mpl is expressed on
hematopoietic cell populations highly enriched in primitive progenitor cells.
Here we summarize and discuss recent studies from our laboratory, as well as
others, demonstrating that TPO has effects on primitive hematopoietic progenitor
cells. When acting alone, TPO stimulates little or no growth, but promotes
viability and suppresses apoptosis of murine multipotent (Lin- Sca-1+) bone
marrow progenitor cells in vitro. In addition, TPO directly and potently
synergizes with other early acting cytokines (kit ligand, flt3 ligand and
interleukin 3) to promote multilineage growth of the same progenitor cell
population. Although it remains to be established whether TPO also acts on the
long-term reconstituting pluripotent stem cells, these studies combined with
progenitor cell studies in c-mpl-deficient mice, suggest that TPO, in addition to
its key role in platelet production, might also have an important impact on early
hematopoiesis.
PMID- 11012219
TI - A new transgenic mouse model for the study of cell cycle control in
megakaryocytes.
AB - During the development of the megakaryocytic lineage, the megakaryoblasts give
rise to megakaryocytes which undergo repeated S phases in the absence of
cytokinesis (endomitosis). The cellular oncogene myc plays a central role in the
proliferation and differentiation of several cell types. In a previous study, we
generated transgenic mice carrying c-myc fused to the estrogen receptor under the
control of the platelet factor four (PF4) megakaryocyte-specific promoter. The
bone marrow of female transgenic mice, but not of male mice, displayed increased
megakaryopoiesis. Here we report that beta-estradiol-induced activation of c-myc
in cultured bone marrow cells derived from male or female transgenic mice
resulted in prolonged survival of the cells in vitro. Addition of a cocktail of
hemopoietic growth factors to beta-estradiol-treated cells, including interleukin
6 (IL-6), IL-3 and stem cell factor further improved the survival time in culture
and increased the percentage of large mature cells, but did not result in
immortalization. The majority of these PF4-expressing cells, however, did not
reach the differentiation stage at which acetylcholinesterase is expressed and
did not appear as large megakaryocytes. We conclude that cultured megakaryocytes
overexpressing myc are induced to proliferate, but have a limited potential to
fully differentiate. Under these conditions, cyclin D3 was downregulated while
the level of cyclin A was slightly upregulated.
PMID- 11012220
TI - The platelet glycoprotein Ib-V-IX system: regulation of gene expression.
AB - Platelet glycoproteins (GPs) Ib-V-IX form the surface receptor for von Willebrand
factor, and this receptor-ligand interaction mediates the shear-dependent
adhesion of platelets to damaged arterial vessel walls. The receptor is a
multicomponent structure consisting of four distinct polypeptides (heterodimeric
GPIb: Ib alpha-Mr143k and Ib beta-Mr22k; GPV-Mr83k; GPIX-Mr20k), and each of the
four cDNAs and genes has been cloned and characterized. The genes appear to have
evolved from a common progenitor genomic sequence related to that encoding GPIX.
They share simple structures with few introns and possess common consensus
regulatory sequences (GATA, ets, Sp-1) in their 5' flanks. Both the GPIb alpha
and the GPIX promoters have been analyzed by transfection of reporter constructs
into hematopoietic and nonhematopoietic cells. The promoters function in a tissue
specific fashion, and gel shift and mutational analyses indicate that GATA and
ets sequences regulate activity. In the case of the GPIX promoter, footprints
confirm the role of the ets-related consensus region. Recent studies of GPIb beta
transcriptional regulation suggest that an aberrant polyadenylation signal,
located in the 3' end of the gene immediately upstream of the GPIb beta gene,
allows in vitro expression of a rare extended fusion transcript encoding both the
upstream protein and GPIb beta. Little detailed information is available in
regard to expression of the GPV gene. In summary, the genes of the GPIb-V-IX
system display features of other megakaryocyte/platelet genes, but the unique
regulatory events that direct the selective expression of these genes in
megakaryocytes remain to be defined.
PMID- 11012221
TI - Hematopoietic differentiation of embryonic stem cells: an in vitro model to study
gene regulation during megakaryocytopoiesis.
AB - We are interested in the regulation of the tissue specificity of the
megakaryocyte-specific platelet glycoprotein IIb gene. The murine embryonic stem
(ES) cells are able to differentiate into erythroid, mast and granulomonocytic
cells in appropriate culture conditions. Our goal is to optimize the production
of myeloid cells including megakaryocytes (MKs) by ES cells. We have found that
coculture with MS-5 stromal cells and the presence of a cocktail of hematopoietic
growth factors (HGFs) [stem cell factor, interleukin 3 (IL-3), IL-6, IL-11, G-CSF
and erythropoietin] had a high synergistic activity on differentiation of ES
cells into pure and MK-containing myeloid colonies from day 12 embryoid bodies.
Thrombopoietin increased the number of MKs only when added to the HGF cocktail in
the presence of MS-5 cells. Interestingly, many MKs exhibited a "hairy"
appearance evocative of pseudopodial proplatelet formation. Expression of genes
specific for the megakaryocytic lineage, GPIIb, PF4, mpl and GPIIIa, was detected
by reverse transcriptase-polymerase chain reaction (RT-PCR) during
differentiation of ES cells, and their relative time course was evaluated. This
demonstrates that optimized culture conditions for the differentiation of ES
cells into the MK lineage provide a useful tool for the study of the regulation
of expression of genes during megakaryocytopoiesis.
PMID- 11012222
TI - Dissecting megakaryocytopoiesis in vivo with toxigenes.
AB - The genetic programs that regulate the commitment of a totipotent stem cell to
the megakaryocytic lineage remain poorly defined and require appropriate in vivo
models. Using a cell-specific obliteration technique, a transgenic mouse model
was produced where perturbations of megakaryocytopoiesis and platelet production
may be induced on demand. This was achieved by targeting the expression of the
herpes virus thymidine kinase (HSV-tk) to megakaryocytes using the regulatory
regions of the gene coding for the alphaIIb gene, an early marker of
megakaryocytopoiesis, which encodes the alpha subunit of the platelet integrin
alphaIIb beta3. The HSV-tk gene is not toxic by itself, but sensitizes the target
cell to the effect of ganciclovir (GCV), leading to the inhibition of DNA
synthesis in dividing cells. The programmed eradication of the megakaryocytic
lineage was induced by treating transgenic mice bearing the hybrid construct
(alphaIIb-tk) with GCV. After 10 days of treatment, the platelet number was
reduced by greater than 96.5% and megakaryocytes were not detectable in the bone
marrow (BM). After discontinuing GCV, BM was repopulated with megakaryocytes, and
the platelet count was restored within seven days. The recovery was accelerated
by the administration of interleukin 11. Prolonged GCV treatment induced
erythropenia in the transgenic mice. Assays of myeloid progenitor cells in vitro
demonstrated that the transgene was expressed in early erythro-megakaryocytic
bipotent progenitor cells. The reversibility and facility of this system provide
a powerful model to determine both the critical events in megakaryocytic and
erythroid lineage development, and for evaluating the precise role that platelets
play in the pathogenesis of a number of vascular occlusive disorders.
PMID- 11012223
TI - Methodologic approaches for investigating human megakaryocyte development at a
molecular level.
AB - Rapid advances in defining the extracellular regulators of megakaryocyte (MK)
development have heightened interest in defining the biochemical and molecular
mechanisms of action of these cytokines. The recent development of molecular
micromethodologies such as in situ hybridization, the polymerase chain reaction,
and the use of antisense oligodeoxynucleotides now make such studies possible in
normal cells. To illustrate the utility of these methods, data gathered using
these methods on developing normal human hematopoietic cells and MKs is
presented. As might be expected, the results obtained demonstrate that growth
factors have complex time and concentration effects on gene expression in
morphologically recognizable human MKs. They also suggest that a more complete
understanding of normal MK development at the molecular level will soon be
possible.
PMID- 11012224
TI - Fibronectin isoforms in megakaryocytes.
AB - Our studies have shown that megakaryocytes (MK) can synthesize fibronectin (FN)
and alternatively spliced fibronectin, FN EIIIB. FN EIIIB is primarily present in
embryonic, proliferating and migrating cells, and thought to be important for
cell maturation. MK, but not nonmegakaryocytic bone marrow cells, contain FN
EIIIB and thus, MK and platelets are among a small number of adult cells and
tissues that synthesize and contain FN EIIIB. Thrombin can induce the secretion
of general FN, but does not cause the secretion of FN EIIIB into the medium.
Analysis of immunostained cells by confocal microscopy revealed that both general
FN and FN EIIIB accumulated on the MK surface following thrombin treatment. Thus,
FN EIIIB can be released only to be bound to the MK surface. The expression of FN
EIIIB on the MK surface may have a unique role in MK migration and maturation.
PMID- 11012225
TI - Regulation of expression of megakaryocyte and platelet proteoglycans.
AB - The existence of proteoglycans in hematopoietic cells has been recognized for
many years. However, elucidation of the structure and function of these molecules
has only begun to be explored in recent years. This paper reviews the current
status of knowledge of the structure, function and metabolism of the serglycin
proteoglycan in megakaryocytes and megakaryocytic tumor cells. We have identified
complex metabolic patterns of the serglycin proteoglycan in terms of regulation
of overall hydrodynamic size, glycosaminoglycan chain length and disaccharide
composition, and processing of the core protein in control cells or in the
presence of phorbol 12-myristate 13-acetate or dimethylsulfoxide. We are
currently studying the regulation of synthesis of this protein by analysis of
promoter constructs in megakaryocytic and non-megakaryocytic hematopoietic cells.
We have also tentatively identified a second proteoglycan, betaglycan, which is
known also as the Type III transforming growth factor beta receptor. We have
identified this molecule in human erythroleukemia and CHRF 288-11 cells by the
presence of characteristic core proteins between 92-120 kDa, by its ability to
adhere to Octyl Sepharose and by detection of mRNA. We hope to apply studies of
proteoglycan metabolism in these cells to understanding the development of alpha
granules and membrane elements in megakaryocytes.
PMID- 11012226
TI - Transcriptional regulation in megakaryocytes: the thrombopoietin receptor gene as
a model.
AB - The MPL gene codes for the thrombopoietin receptor, whose ligand specifically
controls megakaryocytic differentiation. In order to understand the molecular
basis for the megakaryocyte-specific expression of MPL, we analyzed the
regulatory elements of this gene. Two regions are hypersensitive to DNase I in
nuclei of cells that express MPL: the promoter and a portion of intron 6. The
latter behaves as a chromatin-dependent enhancer. A 200 bp fragment of the
promoter is sufficient for high-level specific expression. This fragment can bind
several transacting factors in vitro, including GATA-1 and members of the Ets
family. GATA-1 binds with low affinity to a unique GATA motif at -70 in the MPL
promoter, and destruction of this site yields only a modest decrease in
expression level in human erythroleukemia (HEL) cells. Ets proteins also bind
with low affinity to two sites. One is located at position -15 and its
destruction reduces expression to 50%; the other is located immediately
downstream of the GATA motif and plays a crucial role in expression of the
promoter in HEL cells, as its inactivation reduces expression to 15%. This study
indicates a molecular basis for the coregulation of markers of megakaryocyte
differentiation. Finally, we describe other nuclear factor binding sites that may
be involved in the cell-type-specific expression of MPL.
PMID- 11012227
TI - Platelet immunoregulatory factors.
AB - A number of soluble and membrane-associated proteins are known to mediate
platelet:leukocyte interactions. Platelet-derived factors that have attracted the
most attention to date include transforming growth factor beta, interleukin 1 and
platelet factor 4. Recently, we have uncovered another protein within platelets
that has leukocyte modulatory activity. It was previously characterized as an
endometrial glycoprotein named placental protein 14 (PP14) with suppressive
effects upon lymphocyte proliferation, pro-inflammatory cytokine production and
natural killer cell function. The "hematopoietic" PP14 derived from cells of the
megakaryocytic lineage shares this immunosuppressive property, as evaluated by
two-way mixed lymphocyte cultures. Interestingly, two alternatively spliced
hematopoietic PP14 mRNAs have been cloned which differ in their encoded proteins.
Cell-free translation and transfection analyses have verified the translatability
of both PP14 mRNA species and allowed for the analysis of their glycosylation
properties. PP14, a member of the lipocalin structural superfamily of proteins,
now offers an intriguing new link between the coagulation and immune systems.
PMID- 11012228
TI - In vivo biological effects of various forms of thrombopoietin in a murine model
of transient pancytopenia.
AB - Thrombopoietin (TPO) is the natural regulator of platelet production in the bone
marrow of mammals. This cytokine also seems to play an important role in the
development of the erythroid lineage when recovering from anemic conditions. Here
we study the effects of various TPO molecules on the recovery of hematopoietic
lineages in a mouse model of pancytopenia. Based on previous animal
experimentation and clinical experience with other hematopoietic cytokines, we
found that daily dosing with TPO augmented the recovery of both the megakaryocyte
and erythroid lineages in a mouse model of pancytopenia. However, further
experiments showed that no benefit was gained by using more than a single dose of
recombinant murine (rm)TPO(335) given 24 h after the initiation of the
myelosuppressive treatment. This response to a single dose of rmTPO(335) is dose
dependent. However, the response was attenuated when a truncated, short half-life
TPO molecule (rmTPO[153]) was used. Increasing the half-life of the molecule with
10 kDa polyethylene glycol (PEG) does not improve the response. Only when larger
PEG molecules (20 kDa or 40 kDa) are linked to the rmTPO(153) is the response to
single doses restored to the level of the full-length molecule. These data
suggest that, unlike our experience with other cytokines, the commitment of
progenitors to a megakaryocytic cell line is accomplished by a single short
exposure to TPO.
PMID- 11012229
TI - The clinical development of recombinant human interleukin 11 (NEUMEGA rhIL-11
growth factor).
AB - Completed phase I and II studies of recombinant human interleukin 11 (rhIL-11)
demonstrate its potential as a treatment for chemotherapy-induced
thrombocytopenia. In a phase I study, 16 women with breast cancer received rhIL
11 (10, 25, 50, 75 or 100 microg/kg s.c. once daily) before and during cycles of
moderately dose-intensive chemotherapy. Platelet counts increased in all patients
before chemotherapy. During chemotherapy, the mean platelet count nadirs were
67,000 cells/microl (rhIL-11 10 microg/kg) and greater than 150,000 cells/microl
(25, 50 and 75 microg/kg). Thus, doses of 25 microg/kg and higher appeared to
prevent chemotherapy-induced thrombocytopenia in this study. In a randomized,
placebo-controlled study, rhIL-11 (50 microg/kg) prevented the need for platelet
transfusions during a subsequent chemotherapy cycle in patients who had already
experienced severe chemotherapy-induced thrombocytopenia. Among 82 evaluable
patients, 8 (30%) of 27 patients administered rhIL-11 50 microg/kg avoided
platelet transfusions versus one (4%) of 28 who received placebo (p < 0.05). rhIL
11-treated patients received approximately two-thirds the number of platelet
transfusions that placebo-treated patients received. The median duration of
thrombocytopenia (<50,000 cells/microl) was seven days in rhIL-11-treated
patients compared to 10 days among patients given placebo. This is the first
study in which patients with a history of severe chemotherapy-induced
thrombocytopenia who were receiving a variety of chemotherapy regimens have been
shown to avoid platelet transfusions following the administration of a
thrombopoietic growth factor. This activity of rhIL-11, and the demonstration in
preclinical models that it ameliorates chemotherapy-induced mucositis, have
promoted its further clinical development as a supportive therapy in patients
receiving chemotherapy.
PMID- 11012230
TI - The problem of thrombocytopenia after hematopoietic stem cell transplantation.
AB - Thrombocytopenia after hematopoietic stem cell transplantation (HSCT) is
associated with an increased risk of bleeding and utilization of significant
resources. This review presents an analysis of risk factors associated with
delayed platelet engraftment. The retrospective analysis included 1,468
recipients of autologous or allogeneic transplants treated between January 1,
1990 and July 1, 1995. Risk factors associated with delayed platelet engraftment
after autologous HSCT included use of marrow rather than peripheral blood as the
source of stem cells, being transplanted for acute myeloid leukemia rather than
other diseases, positive patient serology for cytomegalovirus and the presence of
infection post-transplant before engraftment. Risk factors associated with
delayed platelet engraftment after allogeneic marrow transplantation included
unrelated as opposed to related donor transplants, being transplanted for
diseases other than chronic myelogenous leukemia, increased age, onset of acute
graft-versus-host disease (AGVHD), male gender, the administration of
methotrexate for GVHD prophylaxis and the presence of infection before
engraftment. Delayed platelet recovery is associated with decreased survival
after both autologous and allogeneic transplants. Management of delayed platelet
recovery by transfusion of blood products requires significant medical resources
and is of some risk to the patients. Further development of new strategies may
safely reduce the need for blood products. These include peripheral blood stem
cell transplants (allogeneic and autologous), new algorithms for administering
routine platelet transfusions and investigative biological agents for stimulating
megakaryocytopoiesis. Further studies may elucidate the cause of increased
platelet consumption associated with infection and GVHD.
PMID- 11012231
TI - The role of platelet growth factors in cancer therapy.
AB - The use of myeloid growth factors has markedly reduced the complications of
chemotherapy-induced neutropenia, however, abrogation of severe thrombocytopenia
remains a major clinical problem. Platelet transfusions remain the standard
method of preventing or treating thrombocytopenia but are associated with a
variety of complications and are a limited resource. A number of cytokines have
been clinically investigated for their thrombopoietic activity, the most
promising of which is the recently cloned ligand to the hematopoietic growth
factor receptor, c-Mpl. The c-Mpl ligand, also referred to as thrombopoietin,
megakaryocyte growth and development factor (MGDF) and megapoietin, is a potent
lineage-specific agent that promotes growth and maturation of megakaryocytes and
their progenitors. It holds promise for clinical use in the treatment of
iatrogenic or disease-associated bone marrow failure states and possibly in
syndromes of excessive platelet consumption. Early clinical trials assessing the
safety and activity of recombinant human MGDF are now underway.
PMID- 11012233
TI - Fluoroquinolone-resistance in Neisseria gonorrhoeae, Hawaii, 1999, and decreased
susceptibility to azithromycin in N. gonorrhoeae, Missouri, 1999.
AB - In 1999, 360,076 cases of gonorrhea were reported in the United States (1).
Gonorrhea is a major cause of pelvic inflammatory disease, often leading to
ectopic pregnancy and infertility, and it can facilitate human immunodeficiency
virus (HIV) transmission (2). During the 1980s, resistance to penicillin and
tetracycline among gonococcal isolates became widespread; as a result, CDC
recommended that other antimicrobial agents be used to treat gonorrhea. This
report summarizes investigations of an increase in fluoroquinolone-resistant
Neisseria gonorrhoeae in Hawaii and of a cluster of N. gonorrhoeae infections
with decreased susceptibility to azithromycin in Missouri.
PMID- 11012235
TI - What determines benefit from hearing aids?
PMID- 11012234
TI - State-specific changes in singleton preterm births among black and white women-
United States, 1990 and 1997.
AB - National infant mortality rates among non-Hispanic black women are twice those of
non-Hispanic white women (1). Nearly two-thirds of this disparity is attributable
to a higher rate of preterm delivery (PTD) (i.e., < or = 37 weeks' gestation)
among blacks (2). To investigate state-specific changes in PTD rates among blacks
and whites, natality data for 1990 and 1997 were analyzed from 50 states and the
District of Columbia (DC). These data indicated that, although the PTD rate was
twice as high among blacks than among whites, the disparity decreased as the
result of an increase in preterm births among whites and a decrease among blacks
(3).
PMID- 11012236
TI - Distortion product otoacoustic emissions to single and simultaneous tone pairs.
AB - Distortion product otoacoustic emissions (DPOAEs) evoked by single tone pairs and
three simultaneous tone pairs were recorded in 60 normal-hearing adult ears. The
purpose was to replicate a previous study using the commercially available probe
assembly of the Grason Stadler GSI 60 and including ear of presentation in the
statistical analysis along with frequency and condition. DPOAE levels were
comparable between ears and conditions, although differences among frequencies
were found. Noise levels were comparable between ears and tended to increase with
increases in frequency for both conditions. The latter trend was not noted with
the previous study and may be due to differences in the probe assembly and/or
test environment. Further, noise levels were significantly greater at 2,000 and
8,000 Hz in the simultaneous condition. Caution should be exercised when
interpreting results in the simultaneous condition because not all frequencies
may have optimal signal-to-noise ratios when the test is terminated.
PMID- 11012237
TI - Effects of electrode location on speech recognition with the Nucleus-22 cochlear
implant.
AB - Speech recognition performance was measured as a function of electrode in two
experiments with the Nucleus-22 cochlear implant using 4-electrode SPEAK speech
processors. In experiment 1, the four stimulated electrode pairs were shifted in
0.75-mm steps over 3 mm in the apical-basal direction. In experiment 2, the four
electrodes were closely spaced and positioned apically, medially, or basally. An
additional condition spaced the four electrodes as widely as possible. In
experiment 1, City University of New York sentence scores showed a significant
decrease in performance as the electrodes were shifted basally; no other speech
measures showed a significant change with electrode location. For experiment 2,
all scores were the best with the processor that had the electrodes spaced as
widely as possible. In both experiments, all 4-electrode SPEAK processors
produced significantly poorer speech recognition than the subject's own 20
electrode processor. These results indicate that the location of electrodes is an
important factor in implant performance.
PMID- 11012238
TI - Hearing aid benefit in patients with high-frequency hearing loss.
AB - Patients with hearing loss limited to frequencies above 2 kHz are often
considered borderline candidates for hearing aids. In this study, we used the
Profile of Hearing Aid Benefit to access 134 patients' perceived benefit with a
variety of linear hearing aids, some more capable than others at achieving
prescribed frequency gain targets. We also sought to explore various audiologic
and subject factors that might have led patients to report different degrees of
success or failure with their hearing aids. Results demonstrate that subjects
with hearing loss limited to frequencies above 2 kHz benefit significantly from
amplification. However, the amount of benefit reported is mostly unrelated to the
hearing aid gain and frequency response. Of numerous audiologic and demographic
factors explored in the present study, the number of hours of hearing aid use per
day turned out to be the most important single factor that was significantly
related to the amount of reported hearing aid benefit. However, the predictive
value of knowing how many hours per day subjects wore their aids, or any other
combination of factors explored, was quite limited and only accounted for a small
amount of the variability observed in user benefit.
PMID- 11012239
TI - Development and standardization of SCAN-C Test for Auditory Processing Disorders
in Children.
AB - This paper reports on the development and standardization of SCAN-C: Test for
Auditory Processing Disorders in Children-Revised. The revisions include new test
instructions that have been reworded to make them easier for young children,
aural stimuli presented on a compact disc, a revision of the Competing Words
subtest, and the addition of a Competing Sentences subtest. Normative data on the
new test were obtained on 650 children age 5 years, 0 months, to 11 years, 11
months. Analysis of new standardization data revealed systematic improvement in
performance with increasing age. A new method of calculating the composite
standard score gives equal weighting to each subtest of SCAN-C. Subtest test
retest reliability was substantially improved over the original SCAN, with SCAN-C
correlations ranging from .65 to .82 for 5 to 7 year olds. Concurrent validity
tests found that SCAN-C test results can be viewed with the same confidence as
SCAN.
PMID- 11012240
TI - Early-onset sensorineural hearing loss in a child with Turner syndrome.
AB - Turner syndrome is among the more common but less familiar syndromes that include
sensorineural hearing loss and middle ear disease. This article provides a review
of the syndrome, an illustrative case, and a review of specific issues relevant
to audiologic management of patients with Turner syndrome.
PMID- 11012241
TI - Effects of selective serotonin reuptake inhibitors on auditory processing: case
study.
AB - Auditory sensitivity and processing ability were evaluated in a patient who
suffered from hyperacusis, difficulty understanding speech, withdrawn depression,
lethargy, and hypersensitivity to touch, pressure, and light. Treatment with
fluvoxamine and fluoxetine (selective serotonin reuptake inhibitors) reversibly
alleviated complaints. Testing while medicated and unmedicated (after voluntary
withdrawal from medication for several weeks) revealed no difference in pure-tone
thresholds, speech thresholds, word recognition scores, tympanograms, or acoustic
reflex thresholds. Medicated SCAN-A (a screening test for central auditory
processing disorders) results were normal, and unmedicated results were abnormal.
Unmedicated transient otoacoustic emissions and auditory brainstem response waves
I, III, and V were significantly larger bilaterally. Uncomfortable loudness
levels indicated greater tolerance during the medicated condition. Central
processing and vigilance were evaluated with analog-synthesized three-formant
consonant-vowel syllables. While medicated, responses to stimuli at each ear
revealed well-defined, labeling crossovers of about 90 msec. Vowel identification
matched normal subject responses; labeling of /gE/jE/ and /bE/wE/ continua was
well defined but all crossover points differed from normals (p < .0001). During
unmedicated testing, responses to /gE/jE/ began at medicated levels but
approached chance levels for the entire continuum within 10 min; labeling of
/bE/wE/ was consistent with medicated responses throughout with earlier than
normal crossover points.
PMID- 11012242
TI - A vigorous protest.
PMID- 11012244
TI - Dendritic cells: multi-lineal and multi-functional.
PMID- 11012243
TI - A high-resolution view of NK-cell receptors: structure and function.
PMID- 11012245
TI - The biology of recognitive repertoires.
PMID- 11012246
TI - British Society for Matrix Biology Meeting. Aberdeen, 6-7 September 1999.
Abstracts.
PMID- 11012247
TI - Marked cognitive decline in a premorbidly very bright girl after onset of
psychosis.
PMID- 11012248
TI - Early onset schizophrenia in a patient with premature birth, germinal matrix
hemorrhage and periventricular leukomalacia.
PMID- 11012249
TI - Retraction of several recent papers from Dr. Friedhelm Herrmann's laboratories.
PMID- 11012250
TI - CML vaccines as a paradigm of the specific immunotherapy of cancer.
AB - T cells are implicated in the effective control of chronic myeloid leukemia
(CML). Recently, several clinical observations supported by laboratory data,
indicate the presence of CML-specific T cells. Many proteins potentially act as
leukemia-specific antigens for MHC-restricted cytotoxicity in CML. These include
the bcr-abl fusion protein, myeloid-specific differentiation antigens and minor
histocompatibility antigens. There is recent evidence to suggest that bcr-abl
junctional peptides are capable of eliciting both CD4 and CD8 responses in normal
healthy donors and in patients with CML. Moreover, T cell lines can be generated
that react with autologous or HLA-matched fresh CML cells, suggesting that the
bcr-abl fusion protein can be processed and expressed in the MHC cell surface
molecules. Clinical trials exploiting the new understanding of the immunology of
CML are underway.
PMID- 11012251
TI - Gene regulation and deregulation: a beta globin perspective.
AB - The study of the beta globin gene has provided great insights into the mechanisms
of gene regulation and expression. In this review, we consider the normal
regulation and expression of the beta globin gene and illustrate how the various
steps may be affected, providing a basis for understanding the molecular
pathophysiology of beta thalassemia. Mutations causing beta thalassemia can be
classified as beta0 or B+ according to whether they abolish or reduce the
production of beta globin chains. The vast majority of beta thalassemia is caused
by point mutations, mostly single base substitutions, within the gene or its
immediate flanking sequences. Rarely, beta thalassemia is caused by major
deletions of the beta globin cluster. All these mutations behave as alleles of
the beta locus but in several families the beta thalassemia phenotype segregates
independently of the beta globin complex, and are likely to be caused by
mutations in trans-acting regulatory factors.
PMID- 11012252
TI - Reducing the risk of infection from plasma products: specific preventative
strategies.
AB - Collection and testing procedures of blood and plasma that are designed to
exclude donations contaminated by viruses provide a solid foundation for the
safety of all blood products. Plasma units may be collected from a selected donor
population, contributing to the exclusion of individuals at risk of carrying
infectious agents. Each blood/plasma unit is individually screened to exclude
donations positive for a direct (e.g., viral antigen) or an indirect (e.g. anti
viral antibodies) viral marker. As infectious donations, if collected from donors
in the testing window period, can still be introduced into manufacturing plasma
pools, the production of pooled plasma products requires a specific approach that
integrates additional viral reduction procedures. Prior to the large-pool
processing, samples of each donation for fractionation are pooled ('mini-pool')
and subjected to a nucleic acid amplification test (NAT) by, for example, the
polymerase chain reaction (PCR) to detect viral genomes (in Europe: HCV RNA
plasma pool testing is now mandatory). Any individual donation found PCR positive
is discarded before the industrial pooling. The pool of eligible plasma donations
(which may be 2000 litres or more) may be subjected to additional viral screening
tests, and then undergoes a series of processing and purification steps that, for
each product, comprise one or several reduction treatments to exclude HIV, HBV
HCV and other viruses. Viral inactivation treatments most commonly used are
solvent-detergent incubation and heat treatment in liquid phase (pasteurization).
Nanofiltration (viral elimination by filtration), as well as specific forms of
dry-heat treatments, have gained interest as additional viral reduction steps
coupled with established methods. Viral reduction steps have specific advantages
and limits that should be carefully balanced with the risks of loss of protein
activity and enhancement of epitope immunogenicity. Due to the combination of
these overlapping strategies, viral transmission events of HIV, HBV, and HCV by
plasma products have become very rare. Nevertheless, the vulnerability of the
plasma supply to new infectious agents requires continuous vigilance so that
rational and appropriate scientific countermeasures against emerging infectious
risks can be implemented promptly.
PMID- 11012253
TI - Cost effectiveness of sildenafil calls for political discussion.
PMID- 11012254
TI - Debate about medical treatment of life prisoners.
PMID- 11012255
TI - General practitioners have important roles in cancer.
PMID- 11012256
TI - Reviving academic medicine in Britain. More honorary chairs are needed.
PMID- 11012257
TI - Reviving academic medicine in Britain. Research and education must be given equal
weight.
PMID- 11012258
TI - Improving education for senior house officers.
PMID- 11012259
TI - Preventive home visits to elderly people in the community. Visits are most useful
for people aged >/= 75.
PMID- 11012260
TI - Preventive home visits to elderly people in the community. Studies reviewed have
methodical flaws.
PMID- 11012261
TI - Preventive home visits to elderly people in the community. Further research is
needed.
PMID- 11012262
TI - Ethnicity and analgesia in accident departments. Authors did not exclude type II
error or perform power calculation.
PMID- 11012264
TI - Palliative Care Congress. Warwick, United Kingdom, 27-29 March 2000. Abstracts.
PMID- 11012263
TI - Magnets and children--an attractive combination?
PMID- 11012265
TI - [National Days of Laboratory Medicine of Russia. Moscow, October 12-14, 1999.
Workshop: Laboratory Medicine on the Eve of the XXIst Century: synthesis of
traditions and novel trends (analysis, diagnosis, technology, and economy).
Abstracts].
PMID- 11012266
TI - New model law aims to expand criteria used by states for involuntary treatment of
mental illness.
PMID- 11012267
TI - Despite high compliance, GAO survey finds loopholes limit effectiveness of
federal mental health parity law.
PMID- 11012268
TI - Federal oversight of psychiatric hospitals needs to be strengthened, HHS watchdog
concludes after review.
PMID- 11012269
TI - Almost half of Americans report suicide attempt by close friend or relative.
PMID- 11012270
TI - Chasing hyponatraemia in preterm infants.
PMID- 11012271
TI - Low soluble FcRIII receptor demonstrates reduced neutrophil reserves in preterm
neonates.
PMID- 11012272
TI - Suxamethonium is safe in safe hands; mivacurium should also be considered.
PMID- 11012273
TI - Incidence of severe retinopathy of prematurity.
PMID- 11012274
TI - Premedication for intubation in neonates.
PMID- 11012275
TI - Blood pressure standards for very low birthweight infants.
PMID- 11012276
TI - Patient triggered ventilation in neonatal respiratory distress syndrome.
PMID- 11012277
TI - Pyridoxine dependent epilepsy: a suggestive electroclinical pattern.
PMID- 11012278
TI - Parental visiting in neonatal units.
PMID- 11012279
TI - Ureaplasma colonisation and chronic lung disease in neonates.
PMID- 11012280
TI - Stamps in neonatology. Incubators.
PMID- 11012281
TI - [Complement--clinical significance of hypocomplementemia].
PMID- 11012282
TI - A specific electrotherapy technique in the treatment of osteoarthritis of the
knee: three case reports.
PMID- 11012283
TI - Qigong: a personal experience.
PMID- 11012284
TI - [Is palliative non-fractionated radiotherapy really the same as palliative
fractionated radiotherapy?] .
PMID- 11012285
TI - Capture, binding, and detection technologies in clinical diagnostics. Proceedings
and abstracts of the 32nd annual Oak Ridge Conference. 5-6 May 2000, Boston,
Massachusetts, USA.
PMID- 11012286
TI - When You're 24, 34 ... 84?
PMID- 11012287
TI - World cardiovascular disease burden.
PMID- 11012289
TI - 5th National Conference on Anticoagulant Therapy. May 14-15, 1999. Vancouver,
British Columbia, Canada. Proceedings and abstracts.
PMID- 11012288
TI - Myocardial infarction redefined.
PMID- 11012290
TI - [Lipodystrophy syndrome. After 3 years every third patient has lost his fat].
PMID- 11012291
TI - [Nutritional therapy in HIV infection. Many approaches, meager data].
PMID- 11012292
TI - [Switch strategy: replacing the protease inhibitor. Quality of life improves].
PMID- 11012293
TI - [Ritonavir/Saqinavir: dual protease inhibitor combination. Salvage therapy].
PMID- 11012294
TI - Electrical stimulation of the renal nerve neither replicates its natural burst
pattern nor proves the importance of that pattern for renal function.
PMID- 11012295
TI - Changing strategies for treatment of systemic mycoses.
AB - There have been a number of changes in strategies in antifungal therapy in the
past few years. AIDS related mycoses have decreased, and the increase of
fluconazole resistant Candida albicans may be slowing because fewer severely
immune depressed patients require constant fluconazole suppression. Candida
species continue to be relatively common blood culture isolates. About half of
these are C. albicans and half non-albicans species. In recent years, we have
moved from the use of amphotericin B to fluconazole for initial treatment of
candidemia. We have seen fluconazole resistant isolates emerge, primarily C.
glabrata and a few C. krusei, but also C. albicans. It is unclear whether the
increasing use of fluconazole in intensive care units will worsen this problem.
There appears to be no advantage for the lipid formulations of amphotericin B,
though they are useful to reduce or prevent renal toxicity. In the United States
and Europe, prevention and treatment of aspergillosis have become increasingly
important. There are increasing data suggesting that lipid formulations are more
effective for both treatment and prevention of invasive disease in the most
vulnerable patients with this infection. Renal toxicity is reduced but not
avoided by use of the lipid formulations of amphotericin B. For those patients
with less acutely progressing disease, the triazoles may be effective options. It
is unclear at present whether itraconazole, voriconazole, or posaconazole will be
the most favored drug. One promising new class, now in clinical trials, is the
echinocandin group. Other agents, such as the sordarins, the chitin synthase
inhibitors, and topoisomerase inhibitors, have promise but are much earlier in
development. Unfortunately, we still have >50% treatment failure with acute
invasive aspergillosis, and 20%-30% failures with candidemia. Now that we have
multiple classes of antifungal drugs available, and others in preclinical trials,
it would be advantageous to begin more active exploration of combination therapy
with antifungals and with combined immune modulators and antifungals.
PMID- 11012296
TI - Antifungal susceptibility testing: progress and future developments.
AB - The establishment of a standardized broth reference method for antifungal
susceptibility testing of yeasts has opened the door to a number of interesting
and useful developments. The adaptation of the reference macrodilution method to
a microdilution method has significantly increased the clinical utility of
antifungal susceptibility testing, and both methods are now included in the NCCLS
document M27-A. The publication of quality control limits for five antifungal
agents, coupled with the establishment of interpretive MIC breakpoints for three
agents, provides useful parameters to survey clinical isolates of Candida and
other yeast species. Adaptations of the M27 microdilution method for testing
molds has also proved feasible. These developments have made it possible for a
number of recent studies designed to expand the capabilities of laboratories to
perform antifungal susceptibility testing and to enhance our understanding of
trends in antifungal susceptibility. The availability of reference methods also
provides a useful touchstone for the development of commercial products that
promise to be more user friendly and to further improve test standardization.
Products in varying stages of development include two colorimetric microdilution
methods (Sensititre and KPI) and the Etest stable gradient MIC method.
Preliminary data indicate that these methods are viable alternatives to the
reference method for testing of yeasts. Furthermore, Etest may also prove useful
for testing molds. Future expectations for antifungal susceptibility testing
includes improved ability to detect amphotericin B resistance, development of an
NCCLS document for susceptibility testing of molds, and application of these
methods for testing dermatophytes. Incorporation of antifungal susceptibility
testing methods into the clinical trials of new antifungal agents will facilitate
the establishment of clinical correlates and further enhance the clinical utility
of antifungal susceptibility testing.
PMID- 11012297
TI - Atherosclerosis is a paradigmatic disease of the elderly, the roots of which are
laid in youth, whereas the clinically manifested consequences become evident at
old age.
PMID- 11012298
TI - "New" risk factors for atherosclerotic diseases.
AB - Many potential "new" risk factors may predispose to atherosclerotic diseases. The
most promising currently seem to be fibrinogen, C-reactive protein and other
inflammatory markers; hyperhomocysteinemia; low vitamin E intake; insulin
resistance; lipoprotein(a); and fetal undernutrition. However, clinical trial
proof of a causal role between several of these risk factors and CHD may be
difficult to obtain unless selective interventions are developed to lower them.
Certainly, current emphasis for primary and secondary prevention needs to focus
on the established risk factors, particularly those for which clinical trial
evidence has demonstrated interventions are efficacious for CHD prevention.
PMID- 11012299
TI - Early diagnosis and treatment of pancreatic dysplasia in patients with a family
history of pancreatic cancer.
PMID- 11012300
TI - Prospective analysis of endoscopic papillary balloon dilatation and endoscopic
sphincterotomy for removal of common bile duct stones.
PMID- 11012301
TI - Clinical evaluation of endoscopic injection sclerotherapy using N-butyl-2
cyanoacrylate for gastric variceal bleeding.
PMID- 11012302
TI - Gamma-hydroxy butyrate withdrawal delirium: a case report.
PMID- 11012303
TI - Self-inflicted bilateral eye injury by a schizophrenic patient.
PMID- 11012304
TI - Beyond hemiplegia.
PMID- 11012305
TI - The 2nd S. Takahashi Memorial International Workshop on 3-Dimensional Conformal
Radiotherapy. Nagoya, Japan, December 11-13, 1998.
PMID- 11012306
TI - Regarding scoring of radiation pneumonitis.
PMID- 11012307
TI - Defining a uniform biologically effective dose for organs with parallel
architecture.
PMID- 11012308
TI - Fraction size and dose parameters related to the incidence of pericardial
effusions: regarding Martel et al. IJROBP 40(1):155-161; 1998.
PMID- 11012309
TI - Optimizing for the Gamma knife.
PMID- 11012310
TI - Response to Drs. Bauman et al.: pretreatment factors predict overall survival for
patients with low-grade glioma: a recursive partitioning analysis (IJROBP
1997;45[4]:923-929, 1999)
PMID- 11012311
TI - Should the delta-TCP concept be replaced by "local control probability ratios"?
PMID- 11012312
TI - Role of magnesium in alleviating pain: newer insights.
PMID- 11012313
TI - Painful gynecomastia: an unusual toxicity of gabapentin?
PMID- 11012314
TI - Visualization of the vesicular acetylcholine transporter in living cholinergic
cells.
PMID- 11012315
TI - [Spring reunion of the Southwest Delegation of the SFR (SFRIMSO)--French Society
of Radiology and Medical Imaging of the Southwest Region].
PMID- 11012316
TI - [Coordination meeting on the prevention of transfrontier transmission of malaria
in selected countries of the WHO East Mediterranean and European Regions].
PMID- 11012317
TI - [The historical experience of malaria control (on the 75th anniversary of the
resolution of the Soviet People's Commissariat of the RSFSR, Measures for the
Control of Malaria)].
PMID- 11012318
TI - [The current problems of malariology (a survey of the materials from the
international conference on malaria, the MIM African Malaria Conference, Durban,
South Africa, 14-19 March 1999). Multilateral Initiative on Malaria].
PMID- 11012319
TI - Sleep-disordered breathing and hypertension.
PMID- 11012320
TI - Sleep-disordered breathing and hypertension.
PMID- 11012321
TI - Sleep-disordered breathing and hypertension.
PMID- 11012322
TI - Hemodynamic effects of sildenafil.
PMID- 11012323
TI - Use of right precordial leads during exercise testing.
PMID- 11012324
TI - Haptoglobin phenotype and vascular complications in patients with diabetes.
PMID- 11012325
TI - Fortification of foods with folic acid.
PMID- 11012326
TI - Fortification of foods with folic acid.
PMID- 11012327
TI - Fortification of foods with folic acid.
PMID- 11012328
TI - Fortification of foods with folic acid.
PMID- 11012329
TI - Life-threatening toxic epidermal necrolysis with thalidomide therapy for myeloma.
PMID- 11012330
TI - Improvement of Huntington's disease with olanzapine and valproate.
PMID- 11012331
TI - Signal transduction. An arresting tale.
PMID- 11012332
TI - Resuscitation of a choking child in 1841.
PMID- 11012333
TI - Timing and etiology of neonatal cerebral infarction.
PMID- 11012334
TI - Universal neonatal hearing screening.
PMID- 11012336
TI - Cardiopulmonary resuscitation in very low birth weight infants.
PMID- 11012335
TI - Universal neonatal hearing screening.
PMID- 11012337
TI - First urinary tract infections in Swedish children.
PMID- 11012338
TI - Contraception and adolescents.
PMID- 11012339
TI - Current age of onset of puberty.
PMID- 11012340
TI - On looking inward and being scientific: a tribute to G.L. Engle, MD.
PMID- 11012341
TI - Chemoradiation for carcinoma of the cervix: advances and opportunities.
AB - Although it is possible to cure many patients with locally advanced cervical
cancer using radiation therapy alone, loco-regional relapse continues to be a
component of most recurrences. To improve control rates, clinicians have
investigated ways of combining chemotherapy and radiation for more than 30 years.
Despite encouraging results from phase II trials of neoadjuvant chemotherapy,
randomized trials failed to improve on the results with radiation therapy alone.
For a number of reasons, early trials of concurrent chemoradiation were
inconclusive. However, recent reports of five large prospective randomized trials
demonstrated dramatic improvements in survival and local control rates when
cisplatin-containing chemotherapy was given during radiation therapy. These
results also suggest a number of avenues for future research.
PMID- 11012342
TI - Identification of potential mRNA biomarkers in peripheral blood lymphocytes for
human exposure to ionizing radiation.
AB - Since early in the Atomic Age, biological indicators of radiation exposure have
been sought, but currently available methods are not entirely satisfactory. Using
cDNA microarray hybridization to discover new potential biomarkers, we have
identified genes expressed at increased levels in human peripheral blood
lymphocytes after ex vivo irradiation. We recently used this technique to
identify a large set of ionizing radiation-responsive genes in a human cell line
(Oncogene 18, 3666-3672, 1999). The present set of radiation markers in
peripheral blood lymphocytes was identified 24 h after treatment, and while the
magnitude of mRNA induction generally decreased over time, many markers were
still significantly elevated up to 72 h after irradiation. In all donors, the
most highly responsive gene identified was DDB2, which codes for the p48 subunit
of XPE, a protein known to play a crucial role in repair of ultraviolet (UV)
radiation damage in DNA. Induction of DDB2, CDKN1A (also known at C1P1/WAF1) and
XPC showed a linear dose-response relationship between 0.2 and 2 Gy at 24 and 48
h after irradiation, with less linearity at earlier or later times. These results
suggest that relative levels of gene expressions in peripheral blood cells may
provide estimated of environmental radiation exposures.
PMID- 11012344
TI - Mutations induced by alpha-particle radiation--no evidence for a bystander
effect.
PMID- 11012343
TI - Proficient repair of potentially lethal damage sensitive to hypertonic treatment
in osteosarcoma cells.
AB - Fast-repairing potentially lethal damage (PLD) in seven osteosarcoma cell lines
was analyzed after treatment with a hypertonic 0.5 M NaCl solution for 20 min and
compared to that in seven human fibroblast strains. Fixation of PLD after
exposure to ionizing radiation was observed without exception in both the
osteosarcoma cells and the fibroblast strains. The percentages by which the
D(o)'s of the osteosarcoma cells decreased were significantly higher than the
percentage decreases in the C(o)'s of the fibroblast strains (P < 0.01).
Hypertonic treatment resulted in radiosensitization due to fixation of PLD in all
of the osteosarcoma cell lines, demonstrating that osteosarcoma cells can repair
PLD better than normal fibroblast cells. The radiobiological response of the
osteosarcoma cells, with enhanced killing after hypertonic treatment, was similar
to that of normal untreated fibroblast cells.
PMID- 11012345
TI - [Optimizing radiation protection of patients and nurses].
PMID- 11012346
TI - Forensic epidemiology. Vaccine theory of AIDS origins disputed at Royal Society.
AB - At center stage at a meeting on the origin of the AIDS epidemic, held here this
week at the Royal Society, was a controversial theory that a contaminated polio
vaccine tested in Africa more than 40 years ago sparked the epidemic. The theory
took a hit when researchers revealed that tests of old samples of the vaccine
provided no supporting evidence, and the main proponent of the theory, British
writer Edward Hooper, endured a verbal battering himself from several prominent
scientists. But Hooper, unbowed, got in plenty of jabs of his own.
PMID- 11012347
TI - Biomedicine. 'Glue grant' boosts cell signaling consortium.
PMID- 11012348
TI - U.S. postdocs. Report urges better treatment, status.
PMID- 11012349
TI - Appointments. Salk Institute goes north for new CEO.
AB - The revolving door at the top of the Salk Institute for Biological Studies in La
Jolla, California, took another spin last week with the appointment of
neuroscientist Richard Murphy as president and CEO. Murphy, director of the
Montreal Neurological Institute, will become Salk's fourth chief executive in 4
years when he takes up the reins on 1 October. Murphy, 56, says his main job will
be to raise enough money to keep the endowment-poor research institute in the
scientific big leagues.
PMID- 11012350
TI - Molecular biology. Cancer fighter's modus operandi revealed.
AB - Researchers have deciphered how a promising cancer drug acts like a smart bomb,
homing in on only a very narrow range of its potential targets in the cell. The
compound, known as STI-571, has shown remarkable success in early clinical trials
on patients with chronic myelogenous leukemia. Now, in work reported on page
1938, scientists reveal just how the compound works--information that could aid
in the design of similar cancer therapies.
PMID- 11012351
TI - European science. Call to arms for life scientists.
PMID- 11012352
TI - Virology. Evolution on life's fringes.
AB - Earlier this summer, two dozen scientists gathered here to take another crack at
the question of viral origins and evolution. Fresh evidence that viruses have
existed for billions of years suggests that they were on hand when the first
cells arose. That has scientists wondering what role these stripped-down microbes
played in the evolution of life.
PMID- 11012353
TI - Biochemistry. High-tech lures hook into new marine microbes.
AB - Two scientific teams, one of which reports its findings on page 1902, have
identified large populations of bacteria that convert sunlight hitting the sea
surface into energy. These two groups of bacteria, which harness light to move
electrons and power cellular processes, likely help bring energy into the food
chain. And that could help to explain a puzzle that has confounded researchers
trying to understand marine ecosystems: how so many bacteria can survive in the
open ocean, where there seems to be relatively little for them to eat.
PMID- 11012354
TI - Conservation in the real world.
PMID- 11012355
TI - The NIH guidelines on stem cell research.
PMID- 11012356
TI - How to resolve the debate on the origin of AIDS.
PMID- 11012357
TI - An early taste of things to come.
PMID- 11012358
TI - Not-so-simple minds.
PMID- 11012359
TI - PCBs are a health risk for humans and wildlife.
PMID- 11012360
TI - Intellectual property. Publication rights in the era of open data release
policies.
AB - The open data release policy adopted by the large-scale DNA sequencing centers
has made accessible valuable information that facilitates research. Herein, we
argue that the data producers' rights to receive credit for at least some portion
of the analyses of the data must be protected. We suggest that this protection
take the form of a specification of the probable content of the primary paper the
data producers intend to publish when the data gathering is complete. Rights to
publish that paper ought then be restricted to the producers unless they give
permission otherwise.
PMID- 11012361
TI - Evolution. Terrestrial life--fungal from the start?
AB - Fungi have been implicated in the early colonization of land by plants. As
Blackwell explains in her Perspective, Redecker et al.'s discovery of a fossil
fungus provides strong support for this hypothesis. The important role of
symbiotic associations of fungi with plants and animals is increasingly being
recognized, as is the fact that some of these associations date back to the
origin of terrestrial life on Earth.
PMID- 11012362
TI - Cloning. Pigs is pigs.
AB - Since the first report of a cloned animal (Dolly the sheep) 3 years ago, cloning
mammals has become something of a cottage industry. As Prather discusses in his
Perspective, pigs can now be added to the august list of cloned animals, which
includes cows, goats, and mice. This is a particularly spectacular achievement
because pig cloning has turned out to be notoriously difficult. The pig is also a
valuable domestic animal to have cloned because, being physiologically close to
humans, its organs can be used in xenotransplantation.
PMID- 11012363
TI - Neuroscience. Regional differences in cortical organization.
AB - Although there are elegants maps of the human brain that reveal differences in
cellular architecture between different cortical regions, there is not much
information about how corresponding cortical regions differ between the left and
right hemispheres. As Gazzaniga explains in his Perspective, new results reveal
the surprising finding of asymmetry in area 22 (which is important for language
processing) of the left and right hemisphere (Galuske et al.). Clusters of
neurons in area 22 of the left hemisphere are spaced farther apart and have
longer axons cabling them together than neuronal clusters in area 22 of the right
hemisphere.
PMID- 11012364
TI - Tech.sight. Genetic testing--present and future.
PMID- 11012365
TI - [Correct usage of drugs. 8/12--Preparation and administration of injectable
drugs].
PMID- 11012366
TI - [Nursing responsibility. 9/13--The responsibility of the pediatric nurse].
PMID- 11012367
TI - [Management of an imminent home delivery].
PMID- 11012368
TI - [Hygienic care and prevention. 3--shampooing].
PMID- 11012369
TI - PEF versus FEV1.
PMID- 11012370
TI - Caring for indigenous Australian children with asthma.
PMID- 11012371
TI - Differentiation between mitral stenosis and coexisting PPH.
PMID- 11012372
TI - Intravenous montelukast in acute asthma: expensive aminophylline?
PMID- 11012374
TI - Initial platelet activity may predict efficacy after chronic oral glycoprotein
IIb/IIIa blockade: should we still consider uniform treatment regimens?
PMID- 11012373
TI - TB guidelines.
PMID- 11012375
TI - Does clinical significance exist in small platelet aggregates detected by the
laser light scattering method?
PMID- 11012376
TI - The effects of hormone replacement therapy on thrombin generation, fibrinolysis
inhibition, and resistance to activated protein C: prospective cohort study and
review of literature.
AB - Recent studies have found that hormone replacement therapy (HRT) is associated
with a two- to fourfold increased risk of venous thromboembolism, but the
thrombogenic mechanism of HRT remains unclear. To investigate whether HRT use
induces a procoagulant state, we undertook a prospective cohort study in
postmenopausal women to investigate the effects of 3 months of treatment with
oral HRT (conjugated equine estrogen 0.625 mg daily and medroxyprogesterone 2.5
mg daily) on markers of thrombin generation (prothrombin fragment 1+2, thrombin
antithrombin complexes), fibrinolytic potential (plasminogen activator inhibitor
1 (PAI-1) activity), and activated protein C (APC) resistance. In addition, we
reviewed the literature for studies investigating the effects of HRT on markers
of thrombin generation and fibrinolytic potential. In 12 patients who received
HRT for a mean of 3.8 months, there was no significant effect of HRT on levels of
F1+2, thrombin-antithrombin complexes, or the APC ratio. HRT use had the greatest
effect on PAI-1 activity (mean difference = -3.75 UI/mL; 95% confidence interval:
- 8.9, 1.1) compared to other coagulation parameters, but this did not attain
statistical significance (p = 0.12). In the literature review, the effects of HRT
on markers of thrombin generation were inconsistent across studies. There was a
consistent pattern of increased fibrinolytic potential with HRT use associated
with one marker (PAI-1), but not with another marker (tissue plasminogen
activator antigen). We conclude that there is a lack of consistent evidence that
the increased risk of venous thromboembolism associated with HRT use is due to a
procoagulant state related to increased thrombin generation, decreased
fibrinolytic potential, or acquired APC resistance.
PMID- 11012378
TI - [Academician Boris Alekseevich Korolev (on his 90th birthday)].
PMID- 11012377
TI - In vitro characterization of a novel factor Xa inhibitor, RPR 130737.
AB - RPR 130737 inhibited factor Xa (FXa) with a Ki of 2.4 nM and also displayed
excellent specificity toward FXa relative to other serine proteases. It showed
selectivity of more than 1000-fold over thrombin, activated protein C, plasmin,
tissue-plasminogen activator and trypsin. RPR 130737 prolonged plasma activated
partial thromboplastin time and prothrombin time in a dose-dependent fashion. In
the activated partial thromboplastin time assay, the concentrations required for
doubling coagulation time were 0.32 microM (human), 0.61 microM (monkey), 0.44
microM (dog), 0.15 microM (rabbit), and 0.82 microM (rat). The concentrations
required to double prothrombin time were 0.86 microM (human), and 1.26 microM
(monkey), 1.15 microM (dog), 0.39 microM (rabbit) and 7.31 microM (rat). Kinetic
studies revealed that RPR 130737 was a fast binding, reversible and competitive
inhibitor for FXa when Spectrozyme FXa, a chromogenic substrate, was used. A
coupled-enzyme assay measuring thrombin activity following prothrombinase
conversion of prothrombin to thrombin indicated that RPR 130737 was a potent
inhibitor for prothrombinase-bound FXa. In this assay, RPR 130737 showed IC50s of
17 nM and 35.9 nM, respectively when artificial
phosphatidylserine/phosphatidylcholine (PS/PC) liposomes or gel-filtered
platelets were used as the phospholipid source. An FX-deficient plasma clotting
time correction assay further demonstrated that RPR 130737 was a specific
inhibitor of FXa. RPR 130737 showed no effect on platelet aggregation in vitro.
These results indicate that RPR 130737 has the potential to be developed as an
antithrombotic agent based on its potent and selective inhibitory effect against
FXa.
PMID- 11012379
TI - [Cardiac Imaging 2000. Proceedings of a symposium. 4-5 June 1999].
PMID- 11012380
TI - [Fifty years of the Institute of Higher Nervous Activity and Neurophysiology of
the Russian Academy of Sciences].
PMID- 11012381
TI - [42nd Kasseler Symposium on Surgical Diseases of the Bowel. 25-26 June 1999,
Baunatal. Abstracts].
PMID- 11012382
TI - [New vaccines developed in the Russian Federation].
PMID- 11012384
TI - 50th Anniversary Meeting of the Bone and Tooth Society. 10-12 July 2000,
Cambridge, United Kingdom. Abstracts.
PMID- 11012383
TI - [The registration and postregistration control of foreign vaccines].
PMID- 11012385
TI - Possible mechanisms of increased blood viscosity in systemic hypertension.
PMID- 11012386
TI - Arrhythmic right ventricular cardiomyopathy.
PMID- 11012387
TI - A view on the science: physical anthropology at the millennium.
PMID- 11012388
TI - Biomechanics of Mammalian Feeding and Primate Evolution. Proceedings of a
symposium. Research Triangle Park, North Carolina, USA. April 9-13, 1996.
PMID- 11012389
TI - Molecular analysis of Tn1546 in vanA-containing Enterococcus spp. isolated from
humans and poultry.
PMID- 11012390
TI - Establishing criteria for assessment of efficacy of antimicrobial agents in acute
otitis media.
PMID- 11012392
TI - Proceedings of the 21st Symposium on Biotechnology for Fuels and Chemicals. May 2
6, 1999. Fort Collins, Colorado, USA.
PMID- 11012391
TI - Efavirenz-induced decrease in plasma amprenavir levels in human immunodeficiency
virus-infected patients and correction by ritonavir.
PMID- 11012393
TI - Aged dialyzers and vision loss.
PMID- 11012394
TI - Underscoring the importance of mentoring.
PMID- 11012395
TI - Onderstepoort distemper vaccine.
PMID- 11012396
TI - Index of suspicion. Case 3. Acetaminophen overdose.
PMID- 11012397
TI - Stakeholder analysis: a review.
AB - The growing popularity of stakeholder analysis reflects an increasing recognition
of how the characteristics of stakeholders--individuals, groups and organizations
-influence decision-making processes. This paper reviews the origins and uses of
stakeholder analysis, as described in the policy, health care management and
development literature. Its roots are in the political and policy sciences, and
in management theory where it has evolved into a systematic tool with clearly
defined steps and applications for scanning the current and future organizational
environment. Stakeholder analysis can be used to generate knowledge about the
relevant actors so as to understand their behaviour, intentions, interrelations,
agendas, interests, and the influence or resources they have brought--or could
bring--to bear on decision-making processes. This information can then be used to
develop strategies for managing these stakeholders, to facilitate the
implementation of specific decisions or organizational objectives, or to
understand the policy context and assess the feasibility of future policy
directions. Policy development is a complex process which frequently takes place
in an unstable and rapidly changing context, subject to unpredictable internal
and external factors. As a cross-sectional view of an evolving picture, the
utility of stakeholder analysis for predicting and managing the future is time
limited and it should be complemented by other policy analysis approaches.
PMID- 11012398
TI - How to act--implementing health and safety promotion in organizations.
AB - This interdisciplinary review focuses on strategies for implementing health and
safety promotion activities in organizations. Theories are summarized in a
checklist and illustrated by some practical examples from Sweden and abroad. The
points illustrated appear obvious and logical, but they are seldom applied in
practise.
PMID- 11012399
TI - A planning framework for community empowerment goals within health promotion.
AB - Health promotion often comprises a tension between 'bottom-up' and 'top-down'
programming. The former, more associated with concepts of community empowerment,
begins on issues of concern to particular groups or individuals, and regards some
improvement in their overall power or capacity as the important health outcome.
The latter, more associated with disease prevention efforts, begins by seeking to
involve particular groups or individuals in issues and activities largely defined
by health agencies, and regards improvement in particular behaviours as the
important health outcome. Community empowerment is viewed more instrumentally as
a means to the end of health behaviour change. The tension between these two
approaches is not unresolvable, but this requires a different orientation on the
part of those responsible for planning more conventional, top-down programmes.
This article presents a framework intended to assist planners, implementers and
evaluators to systematically consider community empowerment goals within top-down
health promotion programming. The framework 'unpacks' the tensions in health
promotion at each stage of the more conventional, top-down programme cycle, by
presenting a parallel 'empowerment' track. The framework also presents a new
technology for the assessment and strategic planning of nine identified 'domains'
that represent the organizational influences on the process of community
empowerment. Future papers analyze the design of this assessment and planning
methodology, and discuss the findings of its field-testing in rural communities
in Fiji.
PMID- 11012400
TI - Health policy-making in central and eastern Europe: lessons from the inaction on
injuries?
AB - The burden of disease due to injuries has elicited virtually no public health
response in the countries of central and eastern Europe, even though injuries
have long been a much greater problem in the east of Europe than in the west,
with children especially affected. This paper seeks to identify factors that have
inhibited policy development on this topic and to draw lessons for health policy
development in this region more generally. Several factors emerge. Deaths from
injuries have had low visibility. Data have not been assembled in a way that
would facilitate identification of the burden of disease that they constitute.
Those organizations responsible for public health, whether within government or
at local level, were typically very weak with little capacity either to identify
the nature and scale of threats to the health of their populations or to develop
strategies to address them. There was uncertainty about ownership, with
fragmentation of responsibility but no tradition of intersectoral working. Non
governmental organizations, which have placed injuries on the health policy
agenda in the west, are weak or non-existent. International donors, who could
have had a role, have focused on issues such as health care reform. This analysis
provides a potential framework for examining policy responses, or lack thereof,
to other health challenges in this region. It highlights the need for a better
understanding of the potential for using available data, which, in turn, requires
a major strengthening of capacity. However, in many countries, there is a need
for new ways of working, involving a broadening of the sense of ownership, with
clearly designated responsibilities but designed in ways that encourage rather
than inhibit intersectoral action. There is also a need to develop non
governmental organizations that have sufficient capacity to undertake their own
analyses and to place issues on the agenda.
PMID- 11012401
TI - Hospital practices in maternity wards in Lebanon.
AB - This study was conducted in Lebanon with the main objectives of acquiring
baseline data on practices and routines applied in the obstetrics ward for women
having normal delivery; estimating the frequency of certain practices; and
assessing whether women are given choice in these practices. A national sample of
39 hospitals was selected. The director, head midwife, or head nurse of the
obstetrics department was interviewed using a semi-structured questionnaire. The
hospitals studied are largely equipped to cope with emergencies and services are
available 24 hours a day. On average, the caesarean section rate is 18% and the
stillbirth rate is 10 per 1000, but with considerable variability between
facilities. The majority of hospitals do not have written policies or standard
birth procedures and lack mechanisms for evaluation. Generally, minimal prenatal
information is given to women. Companions are allowed during labour but this
access is more restricted in delivery. The reported configuration of professional
care during labour and delivery is favourable to high quality care. In terms of
mobility during labour, most hospitals allow women to move. However, 31 hospitals
set an i.v. drip to all women and some use continuous fetal monitoring method.
Mobility is restricted in delivery; in 23 hospitals women are tied down. Nearly
all hospitals give intra-muscular anaesthesia whereas epidurals are used less
frequently. As for postpartum care, most hospitals do not initiate breastfeeding
within one hour of birth and few have rooming in. The majority of hospitals do
not provide women with family planning methods and a few do not even discuss
methods with them. The approach used in this study constitutes a tool for
understanding and assessing maternity services that should be applied in other
settings. The tool is available from the authors.
PMID- 11012402
TI - Improving the monitoring of immunization services in Kyrgyzstan.
AB - Following the disbanding of the Soviet Union in 1991, the government of
Kyrgyzstan was unable to maintain the previous level of health services. To
revitalize the health services, the Ministry of Health (MOH) first focused on
improving their immunization services, including the immunization component of
the Health Management Information System (HMIS). Secondly, to increase
immunization coverage, the MOH set as a priority the elimination of prescribing
false contraindications to immunization. To accomplish both goals, the MOH
updated the national immunization policies and established a more effective
structure for managing immunization services. To support the MOH, the US Agency
for International Development (USAID) Resources for Child Health (REACH) and
Basic Support for Institutionalizing Child Survival (BASICS) projects provided
technical assistance through a resident coordinator and consultants, and by
organizing an international seminar. The improvements extended beyond systems and
forms, but, instead, emphasized monitoring by the frontline health worker and
supervising the quality of health information. To accomplish their objectives,
the MOH appointed a Working Group to define the problems, revise record-keeping
procedures, and develop monitoring tools. This group, representing both national
and local levels, was composed of MOH epidemiologists, paediatricians and a
management information specialist. To reduce the burden of excessive record
keeping and reporting requirements, the Working Group identified four key
indicators for the service delivery level: (1) DPT3 immunization coverage rates
for children less than 1 year of age; (2) contraindication rates for DPT; (3)
usage of DPT vaccine; and (4) daily refrigerator temperatures. Additional
indicators were included at district and provincial levels. After a successful 1
year trial, the MOH implemented the revised HMIS nationally. Not only did the
quality of the information system improve, but the new approach provided visible
evidence, from facility to national levels, that the MOH was approaching their
objective of reducing contraindication rates for DPT immunizations to 5% or less,
and that vaccine wastage could be substantially reduced. The project demonstrated
that giving health workers the basic epidemiologic skills to monitor their own
work measurably improved the quality of the data, and by acquiring the new
skills, the workers developed a sense of pride in their work.
PMID- 11012403
TI - Financing blood transfusion services in sub-Saharan Africa: a role for user fees?
AB - The provision of a secure and safe blood supply has taken on new importance in
sub-Saharan Africa with the onset of the AIDS epidemic. Blood transfusion
services capable of providing safe blood are not cheap, however, and there has
been some debate on the desirability and sustainability of different financing
mechanisms for blood transfusion services. This paper examines patterns of
financing blood transfusion in three countries--Cote d'Ivoire, Zimbabwe and
Mozambique. It goes on to consider the conceptual options for financing safe
blood, and to examine in detail the possible role of user fees for blood
transfusion in Africa, developing a simple model of their likely burden to
patients based on data from Cote d'Ivoire. The model indicates that, at best,
there can only be a limited role for user fees in the financing of safe blood
transfusion services, due mainly to the relatively high cost of producing a unit
of safe blood. Charging individuals for the blood they receive is likely to be
administratively complex and costly, could realistically recover only a fraction
of the production costs involved, and is further complicated by the fact that the
main recipients of blood transfusion in sub-Saharan Africa are children and
pregnant women. If cost-recovery for safe blood is to be attempted, the most
viable option appears to be that of charging a collective fee, levied upon all
inpatients, not just on those who receive blood. Such a mechanism is not without
problems, not least in its failure to offer incentives for more appropriate blood
use, and it is still likely to recover only a portion of the costs of producing
safe blood. Whether or not cost-recovery is instituted, there will remain an
important role for public funding of blood transfusion services, and, by
implication, an important role for foreign donor support.
PMID- 11012404
TI - The paradox of the cost and affordability of traditional and government health
services in Tanzania.
AB - Since the introduction of user fee systems in the government health facilities of
most African countries, which shifted part of the burden of financing health care
onto the community, affordability of basic health care has been a much discussed
topic. It is sometimes assumed that in areas where high levels of spending for
traditional treatments are common, people would be able to pay for basic health
care at governmental facilities, but may not be willing to do so. However,
examining willingness to pay and ability to pay in the broader context of
different types of illness and their treatment leads us to a very different
conclusion. In the course of a medical-ethnographic study in south-eastern
Tanzania, we found evidence that people may indeed be willing, but may
nevertheless not be able, to pay for biomedical health care--even when they can
afford costly traditional medicine. In this article, we suggest that the ability
to pay for traditional treatment can differ from ability to pay for hospital
attendance for two main reasons. First, many healers--in contrast to the hospital
-offer alternatives to cash payments, such as compensation in kind or in work, or
payment on a credit basis. Secondly, and more importantly, the activation of
social networks for financial help is different for the two sectors. For the poor
in particular, ability to pay for health care depends a great deal on
contributions from relatives, neighbours and friends. The treatment of the
'personalistic' type of illness, which is carried out by a traditional healer,
involves an extended kin-group, and there is high social pressure to comply with
the requirements of the family elders, which may include providing financial
support. In contrast, the costs for the treatment of 'normal' illnesses at the
hospital are usually covered by the patient him/herself, or a small circle of
relatives and friends.
PMID- 11012405
TI - Financing reforms for the Thai health card scheme.
AB - The Thai health card scheme originated from a pilot study on community financing
and primary health care in maternal and child health in 1983. The scheme later
changed to one of voluntary health insurance and finally received a matching
subsidy from the government. The coverage of the scheme is described by a U
curve, i.e. it started with 5% of the total population in 1987, declined to 3% in
1992, with an upturn to 14% in 1997. The upturn has been the result of concerns
about universal coverage policy, together with reforms of fund management. The
provincial fund is responsible for basic health, basic medical, referral, and
accident and emergency services. The central fund takes 2.5% of the total fund to
manage cross-boundary services and high cost care (a reinsurance policy). On
average, the utilization rate of the voluntary health card was higher than that
of the compulsory (social security) scheme. And amongst three variants of health
cards, the voluntary health card holders used health services twice to three
times more than the community and health volunteer card holders. Cost recovery
was low, especially in the provinces with low coverage. In the province with
highest coverage, cost recovery was as high as 90% of the non-labour recurrent
cost. Only 10% of the budgeted fund for reinsurance was disbursed, implying
considerable management inefficiency. The management information system as well
as the management capacity of the Health Insurance Office should be strengthened.
After comparing the health card with other insurance schemes in terms of
coverage, cost recovery, utilization and management cost, it is recommended that
this voluntary health insurance should be modified to be a compulsory insurance,
with some other means of premium collection and minimal co-payment at the point
of delivery.
PMID- 11012406
TI - From state to market: the Nicaraguan labour market for health personnel.
AB - Few countries in Latin America have experienced in such a short period the shift
from a socialist government and centrally planned economy to a liberal market
economy as Nicaragua. The impact of such a change in the health field has been
supported by the quest for reform of the health system and the involvement of
external financial agencies aimed at leading the process. However, this change
has not been reflected in the planning of human resources for health. Trends in
education reflect the policies of past decades. The Ministry of Health is the
main employer of health personnel in the country, but in recent years its
capacity to recruit new personnel has diminished. Currently, various categories
of health personnel are looking for new opportunities in a changing labour
environment where new actors are appearing and claiming an influential role. It
may take more than political willingness from the government to redefine the new
priorities in the field of human resources for health and subsequently turn it
into positive action.
PMID- 11012407
TI - Health sector reform and human resources: lessons from the United Kingdom.
AB - The objective of the paper is to assess the human resource (HR) dimension of the
National Health Service (NHS) reforms in the United Kingdom, and to highlight
lessons for the health systems of countries undergoing reform or restructuring.
Health sector reform in many countries in the 1980s and 1990s has focused on
structural change, cost containment, the introduction of market mechanisms and
consumer choice. This focus has inevitably challenged the ways that health
professionals and other staff are employed and deployed. The methods used to
manage human resources in health care may also in themselves be a major
constraint or facilitator in achieving the objectives of health sector reform.
The impact on the HR function of the NHS reforms is assessed in the paper by
examining three central requirements of the HR function: to maintain effective
staffing levels and skill mix; to establish appropriate employee relations policy
and procedures; and to be involved in pay determination. The paper concludes that
the most significant changes which have occurred as result of the NHS reforms
have been in staffing change and organizational culture, and the individual
attitudes of NHS management and staff. Attempts to alter methods of conducting
employee relations and determining pay and conditions of employment have been
less successful. However, an overall approach to HR management, which would have
been unthinkable in the pre-reform NHS, is now accepted, albeit grudgingly by
some, as the way forward. In general, the changes in the NHS HR function can be
characterized as a partially successful attempt to adopt private sector HR
management techniques to meet the challenges of public sector reform.
PMID- 11012408
TI - The impact of traditional birth attendant training on delivery complications in
Ghana.
AB - OBJECTIVES: In their efforts to reduce maternal and neonatal morbidity and
mortality, many national and international agencies make considerable investments
in training traditional birth attendants (TBAs). The value of TBA training is
controversial, and plausible arguments are made both for and against. Numerous
process evaluations are reported in the literature and the results are mixed,
though generally positive. Outcome evaluations, however, are scarce. This article
describes an outcome evaluation of TBA training conducted in two districts of
Brong-Ahafo Region, Ghana, during 1996. DESIGN AND METHODS: Data from a random
sample survey of 1961 clients of TBAs were subjected to logistic regression
modelling to determine the effect of training on maternal outcomes, controlling
for other independent variables. RESULTS: Of eight outcomes modelled, three were
associated with training and five were not. Three additional outcomes were not
modelled, primarily due to low prevalence. CONCLUSIONS: Despite some inherent
design limitations, this study found that the evidence for a beneficial impact of
TBA training was not compelling. Training sponsors should consider alternative
health investments and, where TBA training remains the intervention of choice, be
realistic about expectations of impact.
PMID- 11012409
TI - A participatory approach to sanitation: experience of Bangladeshi NGOs.
AB - This study assesses the role of participatory development programmes in improving
sanitation in rural Bangladesh. Data for this study came from a health
surveillance system of BRAC covering 70 villages in 10 regions of the country. In
depth interviews were conducted with one adult member of a total of 1556 randomly
selected households that provided basic socioeconomic information on the
households and their involvement with NGO-led development programmes in the
community. The findings reveal that households involved with credit programmes
were more likely to use safe latrines than others who were equally poor but not
involved in such programmes. The study indicates that an unmet need to build or
buy safe and hygienic latrines existed among those who did not own one. Such
latent need could be raised further if health education at the grassroots level
along with supervised credit supports were provided to them. Unlike conventional
belief, the concept of community-managed jointly owned latrines did not seem a
very attractive alternative. The study argues that social and behavioural aspects
of the participatory development programmes can significantly improve
environmental sanitation in a traditional community.
PMID- 11012411
TI - Conferences.
AB - International Conference on Humanization of Childbirth * November 2-4, 2000 *
Fortaleza, Ceara, Brazil The XVth International Conference on the Social Sciences
& Medicine - Societies & Health in Transition * October 16-20, 2000 * Eindhoven,
The Netherlands
PMID- 11012410
TI - A stakeholder analysis.
AB - This paper provides guidance on how to do a stakeholder analysis, whether the aim
is to conduct a policy analysis, predict policy development, implement a specific
policy or project, or obtain an organizational advantage in one's dealings with
other stakeholders. Using lessons learned from an analysis of alcohol policy
development in Hungary, it outlines issues to be considered before undertaking
the stakeholder analysis concerning the purpose and time dimensions of interest,
the time-frame and the context in which the analysis will be conducted. It
outlines advantages and disadvantages of an individual or team approach, and of
the use of insiders and outsiders for the analysis. It describes how to identify
and approach stakeholders and considers the use of qualitative or quantitative
data collection methods for estimating stakeholder positions, levels of interest
and influence around an issue. A key message is that the process of data
collection and analysis needs to be iterative; the analyst needs to revise and
deepen earlier levels of the analysis, as new data are obtained. Different
examples of ways of analyzing, presenting and illustrating the information are
provided. Stakeholder analysis is a useful tool for managing stakeholders and
identifying opportunities to mobilize their support for a particular goal.
However, various biases and uncertainties necessitate a cautious approach in
using it and applying its results.
PMID- 11012412
TI - Publications.
AB - The World Health Organization (WHO) has recently published a booklet of
Guidelines for the Regulatory Assessment of Medicinal Products for use in Self
Medication. The guidelines' purpose is to suggest criteria and methods which drug
regulatory authorities can use in determining the suitability of medicinal
products for self-medication.
PMID- 11012414
TI - Radiology 2000: david G. Disler completes his service as deputy editor
PMID- 11012413
TI - Radiology 2000: ann S. Fulcher, MD, appointed senior deputy editor
PMID- 11012415
TI - Congratulations to the 2000 editorial fellows
PMID- 11012416
TI - Cardiac imaging.
AB - The emergence of noninvasive imaging techniques for the definitive diagnosis and
monitoring of cardiovascular disease has greatly altered cardiac imaging in the
past 25 years. The practice of cardiac imaging in 1975 was centered on
conventional radiography and angiography, but, in the past 2 decades, noninvasive
techniques have substantially replaced catheterization and angiography. The
reliance on echocardiography for the evaluation of many cardiac diseases had a
profoundly negative influence on the role of the radiologist in cardiac imaging,
since the exercise of this modality has been a nearly exclusive province of the
cardiologist. However, in the past decade, magnetic resonance imaging has been
gradually assuming more importance in cardiovascular diagnosis; with this
increase in importance, the role of the radiologist has been reactivated. In
1975, fellowship training in cardiac imaging was frequently combined with
training in angiography. Now, training may be more effective by combining cardiac
and pulmonary imaging in a thoracic imaging fellowship, but cross-training with
an associated subspeciality will be influenced by priorities and personnel in
various departments.
PMID- 11012417
TI - Managed care and social justice.
PMID- 11012418
TI - Dynamic contrast-enhanced MR imaging of the scrotum: reality check.
PMID- 11012419
TI - Posttransplantation lymphoproliferative disorder in children: clinical,
histopathologic, and imaging features.
AB - Posttransplantation lymphoproliferative disorder (PTLD) is a condition in
patients who receive transplants in which chronic immunosuppression leads to an
unregulated expansion of lymphoid cells; the condition ranges from hyperplasia to
malignant lymphoid proliferation. Risk factors affecting the incidence of PTLD
include allograft type, Epstein-Barr virus infection, and immunosuppression. In
this article, we review the clinical, histopathologic, and imaging features of
PTLD in children. Because PTLD can affect nearly any organ system, a wide variety
of clinical manifestations is possible. The heterogeneous nature of the disease
is also reflected on imaging studies. The goals of imaging in patients with PTLD
are to detect disease, guide biopsy, and direct appropriate follow-up imaging
rather than to establish a specific diagnosis. Because the clinical and imaging
manifestations of PTLD are nonspecific and are not reliably predictive of
histopathologic subtype, tissue biopsy is necessary for final diagnosis.
PMID- 11012420
TI - Carotid artery stent placement for atherosclerotic disease: rationale, technique,
and current status.
AB - Carotid arterial endarterectomy is considered to be the standard for the
treatment of atherosclerotic carotid arterial occlusive disease. This has been
validated with results of several randomized controlled trials in which its
effectiveness has been demonstrated over that of the best nonsurgical therapy. In
the past several years, however, carotid angioplasty with stent placement has
emerged as a potential alternative to carotid endarterectomy. This article
represents a critical examination of the rationale for carotid revascularization;
the history of endovascular techniques for the treatment of carotid
atherosclerosis, beginning with balloon angioplasty and evolving to the use of
stents; and the evidence supporting the effectiveness of the endovascular
approach. A brief description of the current technical aspects of carotid artery
stent placement is presented. The future status of the endovascular approach will
be determined with randomized trials in which carotid artery stent placement is
directly compared with endarterectomy, as well as by the potential for further
innovation and improvement in endovascular devices, technique, and safety.
PMID- 11012421
TI - Systemic lupus erythematosus: brain MR imaging and single-voxel hydrogen 1 MR
spectroscopy.
AB - PURPOSE: To evaluate the usefulness of magnetic resonance (MR) imaging and
hydrogen 1 MR spectroscopy in the detection of brain involvement in patients with
systemic lupus erythematosus (SLE) with or without neuropsychiatric symptoms.
MATERIALS AND METHODS: Twenty-six patients who had SLE with (n = 17) or without
(n = 9) neuropsychiatric symptoms were examined at MR imaging and (1)H MR
spectroscopy. The voxel was placed in the basal ganglia and peritrigonal white
matter. Eight healthy volunteers were included. RESULTS: Five of nine patients
with major neuropsychiatric symptoms and one of eight patients with minor
neuropsychiatric symptoms had abnormal MR imaging findings. (1)H MR spectroscopy
showed a significantly decreased N:-acetylaspartate-creatine (Cr) ratio in the
basal ganglia and an increased choline-Cr ratio in the peritrigonal white matter
in patients with major symptoms compared with those with minor symptoms, those
without symptoms, and healthy control subjects. Among patients with major
symptoms, there was no difference in metabolite ratios between those with and
those without abnormal MR imaging findings. Among patients with normal MR imaging
findings, abnormal spectral changes were observed only in those with major
neuropsychiatric symptoms. In patients without neuropsychiatric symptoms, results
of (1)H MR spectroscopy and MR imaging were normal. CONCLUSION: In patients with
SLE, (1)H MR spectroscopic findings seem to reflect the cerebral metabolic
disturbance related to the severity of the neuropsychiatric symptoms and are not
related to the presence of abnormal MR imaging findings.
PMID- 11012422
TI - Intracranial leptomeningeal metastases: comparison of depiction at FLAIR and
contrast-enhanced MR imaging.
AB - PURPOSE: To compare contrast material-enhanced T1-weighted and fluid-attenuated
inversion-recovery (FLAIR) magnetic resonance (MR) images in depicting
leptomeningeal metastases. MATERIALS AND METHODS: Malignant lesions detected at
cytologic examination of cerebrospinal fluid in 70 patients were reviewed. There
were 58 studies in which both FLAIR and contrast-enhanced T1-weighted spin-echo
MR images were available. A senior neuroradiologist reviewed the images from each
sequence individually and separately for signs of leptomeningeal metastases and
assigned a diagnostic rating of positive, indeterminate, or negative. RESULTS:
Leptomeningeal metastases were depicted in 38 cases on contrast-enhanced T1
weighted spin-echo images and in 20 cases on FLAIR images. In three cases,
leptomeningeal metastases were detected by using only FLAIR images. In 20 cases,
leptomeningeal metastases were detected by using only contrast-enhanced T1
weighted spin-echo images. FLAIR imaging has a sensitivity of 34% for
cytologically proved leptomeningeal metastases. Gadolinium-enhanced MR imaging
has a sensitivity of 66%. CONCLUSION: Used alone, contrast-enhanced T1-weighted
images are better than FLAIR images for detecting leptomeningeal metastases. This
is particularly true for cases in which leptomeningeal metastases manifest
primarily or solely as cranial nerve involvement.
PMID- 11012423
TI - Lens of the eye: radiation dose in balloon dacryocystoplasty.
AB - PURPOSE: To evaluate the absorbed radiation dose to the lens of the eye, which is
the critical organ in the primary beam during fluoroscopically guided
transluminal balloon dilation of the lacrimal drainage system (balloon
dacryocystoplasty) for obstructive epiphora and to evaluate the possibility of
deterministic radiation effect on the lens. MATERIALS AND METHODS: The radiation
dose to the lens of the eye during balloon dacryocystoplasty (which includes pre-
and postintervention dacryocystography) was measured in 10 consecutive patients
by using thermoluminescent dosimeters on the lids of both eyes as close as
possible to the lenses. A C-arm angiographic unit coupled with a digital imaging
system was used, with similar exposure and geometric parameters in all cases.
RESULTS: The mean radiation dose to the lens of the treated eye was 4.6 mGy +/-
2.2 (dose range, 1.9-9.1 mGy) and to that of the untreated eye was 38.5 mGy +/-
17.5 (dose range, 14.7-67.8 mGy). CONCLUSION: The lens of the untreated eye
receives a higher dose than that of the treated eye because of its closer
proximity to the x-ray tube in a lateral projection. In the lens, even the
highest measured radiation dose (67.8 mGy) still was well below the deterministic
threshold for lens opacity and cataract formation.
PMID- 11012424
TI - Cost-effectiveness of functional imaging tests in the diagnosis of Alzheimer
disease.
AB - PURPOSE: To evaluate the cost-effectiveness of functional neuroimaging in the
work-up of patients at specialized Alzheimer disease clinics. MATERIALS AND
METHODS: A decision model was used to calculate costs and benefits (in quality
adjusted life-years [QALYs]) that accrued to hypothetical cohorts of patients at
presentation to an Alzheimer disease center. Sensitivity analysis was performed
to examine the effects of diagnostic test characteristics, therapeutic efficacy,
disease severity, and costs on cost-effectiveness. RESULTS: The incremental cost
effectiveness ratio of dynamic susceptibility contrast material-enhanced magnetic
resonance (MR) imaging was $479,500 per QALY (compared with the usual diagnostic
work-up), while visual or quantitative single photon emission computed tomography
(SPECT) was dominated (higher costs, lower effectiveness) by the usual diagnostic
work-up. These results depend critically on the sensitivity and specificity of
the standard diagnostic work-up, the effectiveness of drug treatment, and the
disease severity. Varying these parameters resulted in estimates of incremental
cost-effectiveness for dynamic susceptibility contrast-enhanced MR imaging of
$24,680 to $8.6 million per QALY. SPECT either was dominated by the usual
diagnostic work-up or had cost-effectiveness ratios of $180,200 to $6 million per
QALY. CONCLUSION: The addition of functional neuroimaging to the usual diagnostic
regimen at Alzheimer disease clinics is not cost-effective given the
effectiveness of currently available therapies.
PMID- 11012425
TI - A scale of methodological quality for clinical studies of radiologic
examinations.
AB - PURPOSE: To develop and evaluate a scale for assessment of the methodological
quality for clinical investigations of radiologic studies. MATERIALS AND METHODS:
A scale was developed that included methodological standards compiled from
established sources for assessing the methodological quality of study designs in
clinical research and characteristics related to biases commonly observed in
clinical radiologic research. The scale was composed of 15 standards and was
tested with the results of 96 studies on imaging of liver hemangioma. Interrater
reliability was measured between two observers by using percentage agreement and
kappa statistics. Interrater reliability between two observers for a composite
quality index that encompassed the 15 standards was measured with the intraclass
correlation coefficient. RESULTS: Agreement between the two observers was almost
perfect (kappa value, 0.8-1.0) for 11 standards and substantial (kappa value,
0.74-0.78) for four standards. Agreement between the observers with regard to the
composite quality index also was high (intraclass correlation coefficient r, 0.91
[95% CI: 0.87, 0.94]). CONCLUSION: The scale appears to be reliable for the
assessment of methodological quality of clinical investigations of radiologic
studies.
PMID- 11012426
TI - Nonsurgical management of blunt splenic injury: use of CT criteria to select
patients for splenic arteriography and potential endovascular therapy.
AB - PURPOSE: To determine if contrast material-enhanced spiral computed tomography
(CT) can be used to select patients with blunt splenic injuries to undergo
arteriographic embolization. MATERIALS AND METHODS: During a 15-month period, 78
patients who were hemodynamically stable and required no immediate surgery
underwent contrast-enhanced spiral CT followed by splenic arteriography. CT scans
were assessed for splenic vascular contrast material extravasation or
posttraumatic splenic vascular lesions. Medical records were reviewed for splenic
arteriographic results and clinical outcome. RESULTS: There were 25 grade I, 12
grade II, 27 grade III, 12 grade IV, and two grade V splenic injuries. CT showed
active contrast material extravasation in seven patients and splenic vascular
lesions in 19 patients. At CT, splenic vascular contrast material extravasation
was 100% (seven of seven patients) and a posttraumatic splenic vascular lesion
was 83% (10 of 12 patients) sensitive on the basis of arteriographic or surgical
outcome in predicting the need for transcatheter embolization or splenic surgery.
Overall, CT had a sensitivity of 81% (17 of 21 patients), a specificity of 84%
(48 of 57 patients), negative and positive predictive values of 92% (48 of 52
patients) and 65% (17 of 26 patients), respectively, and an accuracy of 83% (65
of 78 patients) in predicting the need for splenic injury treatment. CONCLUSION:
Contrast-enhanced spiral CT plays a valuable role in selecting hemodynamically
stable patients with splenic vascular injury who may be treated with
transcatheter therapy and potentially improves the success rate of nonsurgical
management.
PMID- 11012427
TI - US vascular mapping before hemodialysis access placement.
AB - PURPOSE: To prospectively assess the effect of preoperative ultrasonographic (US)
mapping on surgical selection, placement of arteriovenous fistulas (AVFs) and
grafts, and negative surgical exploration rates. MATERIALS AND METHODS: US
assessment of the upper extremity arterial and venous anatomy was performed in 70
patients with chronic renal failure before surgical evaluation. The surgeon
documented the planned access procedure, which was based on physical examination
results, and then reviewed the US preoperative mapping report. The surgical
procedure and outcome were recorded. RESULTS: Fifty-two of the 70 patients who
underwent mapping had vascular access placement. Preoperative US mapping resulted
in a change in the planned surgical procedure in 16 (31%) of the 52 patients. An
AVF rather than the planned graft was placed in eight (15%) patients. The AVF
placement rate increased from 32% (126 of 395 patients) to 58% (30 of 52
patients). Unsuccessful surgical explorations decreased from 11% (28 of 256) to
0%. CONCLUSION: Preoperative US mapping before hemodialysis access placement can
result in a change in surgical management, with an increased number of AVFs
placed and an improved likelihood of selecting the most functional vessels
preoperatively. Further study is needed to determine longer term outcomes.
PMID- 11012428
TI - Tunneled infusion catheters: increased incidence of symptomatic venous thrombosis
after subclavian versus internal jugular venous access.
AB - PURPOSE: To compare the incidence of symptomatic venous thrombosis after tunneled
infusion catheter placement via the internal jugular vein (IJV) versus the
subclavian vein (SCV). MATERIALS AND METHODS: A retrospective analysis was
performed of 774 catheters placed. Only patients with complete follow-up were
included, which yielded a population of 279 catheters in 238 patients (166 in the
SCV, 113 in the IJV; total of 26,242 catheter days). All catheters were placed by
interventional radiologists with ultrasonographic (in IJV) or venographic (in
SCV) guidance. RESULTS: Initial complications were limited to one pneumothorax in
the SCV group and one episode of oversedation in the IJV group. There was no
difference in infection rates between the two sites (SVC vs IJV: 0.25 vs 0.32 per
100 catheter days; P >.99). The mean dwell time was slightly longer for SCV
catheters (103 days) than for IJV catheters (79 days) (P =.04). Venous thrombosis
developed in 13% of patients (0.12 per 100 catheter days) with an SVC catheter
placed as compared with in 3% (0.04 per 100 catheter days) with an IJV catheter
(P =.018). This difference persisted after adjustment for catheter size and side
of placement (P =.025). The mean time to thrombosis was 36 days for SCV catheters
and 142 days for IJV catheters. CONCLUSION: The IJV is the preferred site for
tunneled infusion catheter placement because of the lower incidence of
symptomatic venous thrombosis.
PMID- 11012429
TI - Peripheral arterial obstruction: prospective study of treatment with a
transluminally placed self-expanding stent-graft. International Trial Study
Group.
AB - PURPOSE: To evaluate the safety and efficacy of an endoluminal prosthesis for
treatment of peripheral arterial occlusive disease (PAOD). MATERIALS AND METHODS:
A self-expanding endoprosthesis with an expanded polytetrafluoroethylene tube
inside a nitinol support structure was implanted in 127 patients with symptomatic
PAOD in the iliac (61 limbs) and femoral arteries (80 limbs). Clinical category
status, ankle-brachial index, and color duplex flow imaging results were recorded
before treatment, at discharge, and at 1, 3, 6, and 12 months after treatment.
Aspirin was administered throughout the study, and heparin was administered
during and for 2 days after the procedure. RESULTS: Endoprosthesis deployment was
technically successful in all patients. Complications occurred in 24 of 141
procedures and included three major complications. Early thrombosis (within 30
days) occurred in one iliac and three femoral arteries. Late restenosis or
reocclusion was observed in five iliac and 14 femoral arteries within the 1st
year. Primary patency rates in iliac arteries were 98% +/- 3% (standard error)
and 91% +/- 4%, respectively, at 6 and 12 months after treatment. Primary patency
rates in femoral arteries were 90% +/- 3% and 79% +/- 5%, respectively, at 6 and
12 months. Secondary patency rates were 95% and 93% for iliac and femoral
arteries, respectively, at 12 months after treatment. CONCLUSION: The device used
in this study can be implanted without additional risks to the patient and
provided encouraging patency rates up to 1 year.
PMID- 11012430
TI - Peripheral arterial disease: meta-analysis of the diagnostic performance of MR
angiography.
AB - PURPOSE: To summarize the overall diagnostic performance of magnetic resonance
(MR) angiography in the evaluation of peripheral arteriosclerotic occlusive
disease and to identify the most important sources of variation in diagnostic
accuracy between studies. MATERIALS AND METHODS: A search strategy in MEDLINE and
citation tracking were used to identify relevant English-language articles
published since 1991. Each article was critically appraised for examination,
patient, and study design characteristics. The accuracy data from different
studies were analyzed by constructing summary receiver operating characteristic
curves; multiple linear regression was used to examine the variation between
study results. RESULTS: Twenty-three studies were included. There was much
heterogeneity in the study results, which could not be explained as differences
in the threshold for a positive result. About half of the variation was due to
the type of MR angiographic examination and the extent of image evaluation. The
relative diagnostic odds ratio (DOR) for three-dimensional (3D) gadolinium
enhanced MR angiography compared with two-dimensional (2D) time-of-flight MR
angiography was 7.46 (95% CI: 2.48, 22.20). The relative DOR for review of
transverse source images or multiplanar reformations in addition to maximum
intensity projections (MIPs) compared with the use of only MIPs for image
evaluation was 4.53 (95% CI: 1.46, 13.87). CONCLUSION: The diagnostic accuracy of
3D gadolinium-enhanced MR angiography is superior to that of 2D time-of-flight MR
angiography. Also, the review of transverse source images or use of additional
postprocessing techniques, such as multiplanar reformation, results in
significantly better diagnostic performance.
PMID- 11012431
TI - Suppression of intravascular signal on fat-saturated contrast-enhanced thoracic
MR arteriograms.
AB - PURPOSE: To assess the prevalence of artifactual signal intensity loss within the
aortic arch and proximal branch vessels on fat-saturated contrast material
enhanced magnetic resonance (MR) arteriograms of the thoracic aorta and to
hypothesize about the cause of the loss of signal intensity. MATERIALS AND
METHODS: Between January and June 1998, 105 consecutive MR arteriograms of the
thoracic aorta were acquired in 103 patients at 1.5 T. Imaging included an
arterial phase three-dimensional (3D) fat-saturated contrast-enhanced gradient
echo (GRE) sequence followed by a delayed two-dimensional (2D) transverse fat
saturated GRE sequence. All MR images were reviewed by two radiologists who were
blinded to patient history and results of imaging studies and who evaluated the
images for the presence of intraluminal loss of signal intensity in the aortic
arch and the proximal branch vessels. RESULTS: Intravascular loss of signal
intensity was present in at least one vessel on 23 of the 105 arterial phase 3D
studies. Seventy-one of 91 left subclavian arterial segments had loss of signal
intensity on the delayed 2D studies. CONCLUSION: Intravascular signal intensity
loss can be present on contrast-enhanced fat-saturated images of the aortic arch
and proximal branch vessels, particularly the left subclavian artery. This
phenomenon, which is to the authors' knowledge previously unreported and which is
hypothesized to result from undesired water saturation, should not be
misinterpreted as stenotic or occlusive vascular disease.
PMID- 11012432
TI - Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular
carcinoma after occlusion of tumor blood supply.
AB - PURPOSE: To evaluate the usefulness of percutaneous radio-frequency (RF) thermal
ablation of nonresectable hepatocellular carcinoma (HCC) after occlusion of the
tumor arterial supply. MATERIALS AND METHODS: Sixty-two patients with cirrhosis
and biopsy-proved HCC underwent RF ablation after interruption of the tumor
arterial supply by means of occlusion of either the hepatic artery with a balloon
catheter (40 patients) or the feeding arteries with gelatin sponge particles (22
patients). RESULTS: After a single RF procedure in 56 patients and after two
procedures in six patients, spiral computed tomography (CT) demonstrated a
nonenhancing area corresponding in shape to the previously identified HCC, which
was suggestive of complete necrosis. No major complications occurred. Two
patients subsequently underwent surgical resection; the remaining 60 patients
were followed up with spiral CT. During a mean follow-up of 12.1 months, 11 HCC
nodules showed areas of local progression; 49 were identified as nonenhancing
areas with a 40%-75% reduction in maximum diameter. The 1-year estimate of
failure risk was 19% for local recurrence and 45% for overall intrahepatic
recurrence. The estimated 1-year survival was 87%. Histopathologic analysis of
one autopsy and two surgical specimens revealed more than 90% necrosis in one
specimen and 100% necrosis in two. CONCLUSION: HCC nodules 3.5-8.5 cm in diameter
can be ablated in one or two RF sessions after occlusion of the tumor arterial
supply.
PMID- 11012433
TI - Serum ethanol levels in children and adults after ethanol embolization or
sclerotherapy for vascular anomalies.
AB - PURPOSE: To evaluate the serum ethanol level in children and adults after ethanol
embolization or sclerotherapy for vascular anomalies. MATERIALS AND METHODS:
Serum ethanol level was evaluated in 71 patients with vascular anomalies who
underwent ethanol embolization, sclerotherapy, or both. Blood used to determine
serum ethanol level was drawn at the end of each procedure. RESULTS: The
relationship between serum ethanol level and amount of ethanol administered was
statistically significant. Results of stepwise linear regression analysis showed
that the amount of ethanol administered (P <.001) and type of malformation (P
=.02) were multivariate predictors of serum ethanol level. Results of logistic
regression analysis revealed that the only uni- or multivariate predictor of
legal intoxication was the amount of ethanol administered (P =.018). Five
patients fulfilled the criteria for legal intoxication, and the mean amount of
ethanol administered to these patients was 0.87 mL per kilogram of body weight +/
0.18 (SD) (range, 0.55-0.99 mL/kg). CONCLUSION: The volume of ethanol
administered is the most reliable predictor of serum ethanol level and legal
intoxication. Patients who receive up to 1.0 mL/kg ethanol during embolization or
sclerotherapeutic procedures may have elevated serum ethanol levels that could
put them at risk of respiratory depression, cardiac arrhythmias, seizures,
rhabdomyolysis, and hypoglycemia.
PMID- 11012434
TI - Case 31
PMID- 11012435
TI - Case 27: intrapancreatic accessory spleen.
PMID- 11012436
TI - Heterotopic pancreas in the stomach: CT findings.
AB - PURPOSE: To describe the computed tomographic (CT) findings of heterotopic
pancreas in the stomach. MATERIALS AND METHODS: CT findings in 12 patients with
heterotopic pancreas in the stomach were reviewed. Surgical resection (n = 11) or
endoscopic excision (n = 1) was performed in cases of symptomatic heterotopic
pancreas (n = 4), suspected submucosal tumors (n = 7), and gastric carcinoma (n =
1). Seven patients underwent helical CT with water as an oral contrast agent;
five underwent nonhelical CT with water-soluble contrast material. RESULTS: Nine
heterotopic pancreata were in the antrum and one each was in the body, fundus,
and perigastric fat. Seven lesions were on the greater curvature aspect; five, on
the lesser curvature aspect. Common CT findings were well-defined oval or round
masses with smooth or serrated margins in the gastric antral wall. Four of the
seven lesions in which helical CT was performed enhanced similarly to normal
pancreas. Preoperatively, CT depicted 11 of the 12 lesions, but CT findings were
interpreted correctly as heterotopic pancreas in only two; the remaining 10 were
misinterpreted as other lesions. Atypical findings were cystic dilatation of
heterotopic pancreatic duct in two, unusual location in the fundus or perigastric
fat in two, and malignant transformation in one. CONCLUSION: CT findings of
heterotopic pancreas in the stomach appear to be nonspecific for diagnosis,
except for location.
PMID- 11012437
TI - Fibrolamellar hepatocellular carcinoma: pre- and posttherapy evaluation with CT
and MR imaging.
AB - PURPOSE: To determine the features of advanced hepatic and extrahepatic
fibrolamellar hepatocellular carcinomas (HCCs) and their effects on immediate
surgical management and tumor recurrence. MATERIALS AND METHODS: Thirty-one
patients with fibrolamellar HCC underwent pretherapy computed tomography (CT); 11
underwent pretherapy magnetic resonance (MR) imaging. All 40 patients underwent
posttherapy CT; four, follow-up MR imaging. Imaging, surgical, and
histopathologic findings were correlated. RESULTS: Twenty-five (81%) patients had
solitary tumors (mean maximum diameter, 13 cm). Thirteen (42%) patients had
intrahepatic biliary obstruction; 27 (87%) patients had involvement of the portal
or hepatic veins. Thirteen (42%) had extrahepatic tumor spread, nine (29%) had
distant metastases on pretherapy images, and 20 (65%) had lymphadenopathy. Thirty
two (80%) of 40 patients underwent exploration surgery; curative resection was
attempted in 25 (62%), including four patients who underwent liver
transplantation. Only 17 patients were considered to have had hepatic and
extrahepatic tumors completely excised. Tumor recurred in all eight of the 17
patients who had extrahepatic disease at pretherapy CT and in four of the seven
patients who seemed to have tumor limited to the liver. A combination of repeat
tumor resection and adjuvant chemotherapy resulted in prolonged tumor-free
survival in some cases. CONCLUSION: Fibrolamellar HCC frequently demonstrates
aggressive local invasion and nodal and distant metastases. Pretherapy and follow
up imaging are important for staging, surveillance, and optimal management.
Aggressive surgical resection may be helpful to control fibrolamellar HCC and to
prolong survival in appropriately selected cases.
PMID- 11012438
TI - Hepatic lesion detection and characterization: value of nonenhanced MR imaging,
superparamagnetic iron oxide-enhanced MR imaging, and spiral CT-ROC analysis.
AB - PURPOSE: To determine the accuracy for detection and characterization of focal
hepatic lesions of nonenhanced, superparamagnetic iron oxide (SPIO)-enhanced, or
a combination of nonenhanced and SPIO-enhanced MR imaging and contrast-enhanced
spiral computed tomography (CT). MATERIALS AND METHODS: Spiral CT and T2-weighted
SPIO-enhanced (ferucarbotran-enhanced) MR imaging were performed in 35 patients
within 2 weeks before surgery for malignant hepatic lesions. Only malignant
lesions with histopathologic proof were considered. A total of 875 images with
and 800 images without focal lesions were presented to five readers, who were
asked to assess the presence and characterization of lesions by using a five
point confidence scale. Receiver operating characteristic analysis was performed.
RESULTS: Nonenhanced and SPIO-enhanced images together and SPIO-enhanced images
alone yielded the best performance for lesion detection. No differences were
found among all imaging techniques with regard to lesion characterization (benign
vs malignant). The combined approach resulted in larger area under the ROC curve
(A(z) = 0.9062) and accuracy (85.3%) (P < 0.02), as compared with SPIO-enhanced
MR imaging (A(z) = 0.8667; accuracy, 73.1%). CONCLUSION: SPIO-enhanced T2
weighted MR imaging was more accurate than nonenhanced T1-weighted and T2
weighted MR imaging and contrast-enhanced spiral CT for the detection of focal
hepatic lesions. The combined analysis of nonenhanced and SPIO-enhanced images
was more accurate in the characterization of focal hepatic lesions than was
review of SPIO-enhanced images alone.
PMID- 11012439
TI - Right lower quadrant pain and suspected appendicitis: nonfocused appendiceal CT-
review of 100 cases.
AB - PURPOSE: To determine the value of standard, nonfocused computed tomography (CT)
in examining patients with right lower quadrant (RLQ) pain and suspected
appendicitis. MATERIALS AND METHODS: The CT scans and medical records of 100
consecutive patients who presented to the emergency department with RLQ pain and
were clinically suspected of having appendicitis were retrospectively reviewed.
Helical CT of both the abdomen and pelvis was performed at 7-mm increments after
oral and intravenous contrast material administration. CT scans were evaluated
for the presence of appendiceal or other disease. Results were correlated with
surgical and pathologic findings in 34 patients or with 3-month clinical follow
up in 66 patients. RESULTS: CT depicted abnormalities in 66 patients (66%). In 59
(59%) patients, the abnormality was located in the pelvis; 23 (39%) of these
patients had appendicitis. Seven (7%) patients had abnormalities outside of the
pelvis, a region not typically scanned during focused appendiceal imaging. Four
of these seven patients required surgery. Thus, if only pelvic focused RLQ CT had
been performed, overall sensitivity would have decreased from 99% to 88% (P <.05)
and sensitivity for cases necessitating surgery would have decreased from 96% to
82% (P <.05). CONCLUSION: Both abdominal and pelvic CT examinations are necessary
to increase sensitivity and identify the many possible causes of RLQ pain in
patients with clinically suspected appendicitis.
PMID- 11012440
TI - Influence of image acquisition parameters on CT artifacts and polyp depiction in
spiral CT colonography: in vitro evaluation.
AB - PURPOSE: To quantify the effects of spiral computed tomographic (CT) acquisition
parameters on the magnitude of three-dimensional (3D) rippling artifacts and
polyp depiction. MATERIALS AND METHODS: An in vitro colon phantom was constructed
with air-filled acrylic cylinders that contained synthetic polyps of 3-13 mm. The
phantom was submerged in fluid and positioned at four angles of inclination
relative to the z axis. Image data were acquired at collimation and pitch
combinations of 3 mm and 1.67 and 5 mm and 1.6, respectively. Rippling artifacts
were quantified by measuring the longitudinal variation of in-plane phantom edge
width, and the influence of these artifacts on the depiction of pedunculated and
sessile polyps was assessed qualitatively. RESULTS: The in-plane magnitude of the
rippling artifact was a function of the angle of inclination relative to the
longitudinal axis and the table increment. The through-plane periodicity of the
artifact was equal to one-half the table increment. CONCLUSION: The table
increment and angle of inclination of the surface of the object relative to the z
axis determine the periodicity and magnitude of the rippling artifact at 3D
spiral CT colonography. Although the depiction of small pedunculated polyps was
not compromised, some sessile polyps were degraded by the artifact.
PMID- 11012441
TI - Stent appearance at contrast-enhanced MR angiography: in vitro examination with
14 stents.
AB - PURPOSE: To evaluate signal intensity changes influencing assessment of stent
patency at contrast material-enhanced magnetic resonance (MR) angiography.
MATERIALS AND METHODS: By using an in vitro model, 14 stents-nine nitinol, one
tantalum, two stainless steel, and two cobalt alloy-were investigated regarding
their appearance at MR imaging. A vascular phantom consisting of tubes filled
with 2.00 mmol/L gadopentetate dimeglumine in saline solution was studied in
different orientations within the magnetic field. Imaging was performed with a
fast three-dimensional gradient-echo sequence (4. 70/1.89 [repetition time
msec/echo time msec]). Relative signal intensity reduction within the stents and
the degree of artificial narrowing of the stent lumen were calculated. RESULTS:
The stent lumen was visible within 13 stents. A total signal void inside the
stent lumen appeared in only one cobalt alloy stent. Artificial narrowing of the
diameter was less than 33% in 10 of 14 stents. The tantalum stent and four
nitinol stents seemed best suited for contrast-enhanced MR angiography. A
bandlike artifact occurred at the ends of the stents when positioned along the
readout direction. CONCLUSION: To differentiate between artifacts and stenoses,
knowledge of the degree of signal intensity reduction and artificial lumen
narrowing within vascular stents is essential. Stent geometry, relative
orientation to the magnetic field, and alloy composition influence signal
intensity alteration within the stent lumen.
PMID- 11012442
TI - CT of the middiaphyseal femur: cortical bone mineral density and relation to
porosity.
AB - PURPOSE: To determine whether computed tomography (CT) can be used to quantify
age- and site-related changes in cortical bone mineral density (cBMD) at the
middiaphyseal femur and whether cBMD differences are related to intracortical
porosity. MATERIALS AND METHODS: Cortical bone specimens from 163 femurs were
studied with CT and microradiography. Femurs were from 77 males and 86 females in
a white anthropologic collection covering a broad age spectrum. In each sample,
the cBMD was measured in the entire cortical width and in periosteal,
midcortical, and endosteal subregions of interest. Age- and site-related changes
in cBMD were tested for significance by using a two-way analysis of variance for
both sexes. By using linear regression, cBMD was compared with porosity in the
entire cortical width and in each subregion. RESULTS: There were significant age
related differences in cBMD (P <.001 in females, P =.008 in males). In addition,
cBMD values were significantly different between the three cortical subregions (P
<.001 for both sexes), decreasing from the periosteum to the midcortex to the
endosteum. The cBMD values were closely related to porosity, and porosity
contributed to 71.6% of the variance in cBMD in the overall population.
CONCLUSION: CT is effective in the measurement of age- and site-related changes
in cBMD. Decreases in cBMD are closely correlated with increased cortical
porosity.
PMID- 11012443
TI - Femoral head osteonecrosis: detection and grading by using a rapid MR imaging
protocol.
AB - PURPOSE: To design and evaluate a limited magnetic resonance (MR) imaging
examination that can be performed rapidly and potentially inexpensively in
patients with clinical suspicion of osteonecrosis. MATERIALS AND METHODS: Both a
limited and a full hip MR examination were performed prospectively in 179 hips in
92 patients with clinical suspicion of femoral head osteonecrosis. The presence
of osteonecrosis was determined by two radiologists. The percentage of
involvement of the femoral head weight-bearing surface was evaluated subsequently
for osteonecrosis-positive hips on both sets of images. RESULTS: Both
examinations were performed successfully in all cases. Agreement between the
limited and full examinations for presence of osteonecrosis was 98.9% (177 of 179
cases; kappa, 0.97). Forty-six (92%) of 50 patients with femoral head
osteonecrosis at both examinations were placed in the appropriate quartile of
percentage of femoral head weight-bearing surface involvement by both readers
(weighted kappa, 0.94). Incidental findings were made at the full examination
that could not be made or were difficult to make at the limited examination.
CONCLUSION: There was excellent agreement between the full and screening MR
examinations for both detection of and determining the extent of osteonecrosis.
The time and potential cost reduction achieved with a limited examination may
allow introduction of MR imaging earlier in the diagnosis of femoral head
osteonecrosis, as well as its more widespread use in patient care.
PMID- 11012444
TI - Characterization of the "red zone" of knee meniscus: MR imaging and histologic
correlation.
AB - PURPOSE: To determine the extent and vascularity of knee menisci with
conventional and gadolinium-enhanced magnetic resonance (MR) imaging in cadaveric
specimens, with histologic findings as the reference standard, and to investigate
signal intensity changes in menisci and perimeniscal soft tissues in symptomatic
patients. MATERIALS AND METHODS: Radial dimensions and enhancement patterns of
menisci were recorded and compared in (a) 12 cadaveric menisci examined with
conventional and gadolinium-enhanced intermediate-weighted and fat-suppressed T1
weighted spin-echo MR imaging, high-spatial-resolution T1-weighted and fast low
angle shot MR imaging, and gross anatomic and histologic specimens and (b) 18
patients examined with conventional and gadolinium-enhanced fat-suppressed T1
weighted spin-echo MR imaging. RESULTS: No differences in radial measurements of
the meniscus were found for different MR techniques (P =.551). Despite the
presence of vessels in the peripheral 10%-15% of the menisci, no enhancement of
menisci was detected in specimens or patients. Perimeniscal soft-tissue
enhancement adjacent to the posterior horn was greater than that adjacent to the
anterior horn (P <.05), and enhancement of the lateral meniscal body was greater
than that of the medial meniscal body (P <.05). CONCLUSION: The wedge-shaped low
signal-intensity structure seen on MR images represents the entire meniscus.
Intravenous injection of contrast material does not appear to be useful for
differentiation of the vascularized from the nonvascularized zone of the
meniscus.
PMID- 11012445
TI - Pulley system in the fingers: normal anatomy and simulated lesions in cadavers at
MR imaging, CT, and US with and without contrast material distention of the
tendon sheath.
AB - PURPOSE: To describe the normal anatomy of the finger flexor tendon pulley
system, with anatomic correlation, and to define criteria to diagnose pulley
abnormalities with different imaging modalities. MATERIALS AND METHODS: Three
groups of cadaveric fingers underwent computed tomography (CT), magnetic
resonance (MR) imaging, and ultrasonography (US). The normal anatomy of the
pulley system was studied at extension and flexion without and with MR
tenography. Pulley lengths were measured, and anatomic correlation was performed.
Pulley lesions were created and studied at flexion, extension, and forced
flexion. Two radiologists reviewed the studies in blinded fashion. RESULTS: MR
imaging demonstrated A2 (proximal phalanx) and A4 (middle phalanx) pulleys in 12
(100%) of 12 cases, without and with tenography. MR tenography showed the A3
(proximal interphalangeal) and A5 (distal interphalangeal) pulleys in 10 (83%)
and nine (75%) cases, respectively. US showed the A2 pulley in all cases and the
A4 pulley in eight (67%). CT did not allow direct pulley visualization. No
significant differences in pulley lengths were measured at MR, US, or pathologic
examination (P: =.512). Direct lesion diagnosis was possible with MR imaging and
US in 79%-100% of cases, depending on lesion type. Indirect diagnosis was
successful with all methods with forced flexion. CONCLUSION: MR imaging and US
provide means of direct finger pulley system evaluation.
PMID- 11012446
TI - The musculoskeletal crescent sign.
PMID- 11012447
TI - Rectal bleeding after radiation therapy for prostate cancer: endoscopic
evaluation.
AB - PURPOSE: To analyze the frequency and clinical importance of proctitis and
hematochezia after radiation therapy for prostate cancer. MATERIALS AND METHODS:
Of 63 patients with prostate cancer treated with curative intent by a single
radiation oncologist between July 1, 1993, and December 31, 1997, 30 were
asymptomatic, but 33 had heme-positive digital rectal examination (DRE) results
or hematochezia at routine follow-up. Twenty-six of these patients underwent
endoscopy of the sigmoid colon or colon for evaluation of these symptoms. Median
doses of 60.0 Gy at postoperative radiation therapy and 68.4 Gy at definitive
radiation therapy were delivered to four fields daily by using blocking
customized on the basis of computed tomographically documented evidence of
disease. The Fisher exact test and the Kaplan-Meier method were used to analyze
the results. RESULTS: The frequency of rectal bleeding approached 80% at 3 years
after radiation therapy in definitively treated patients. Only 14 patients had
proctitis: eight as the only sign, and six in association with other disease. Six
patients had other disease without proctitis, and four patients had normal
examination findings. The frequency of rectal bleeding in the presence of
proctitis was similar to that in the presence of other disease (Fisher exact
test, P =.68). CONCLUSION: Hematochezia or positive DRE findings are frequent
sequelae of definitive radiation therapy for prostate cancer; however, causes
other than proctitis are often documented at endoscopy. Symptomatic individuals
warrant rigorous evaluation to rule out serious coexistent disease.
PMID- 11012448
TI - Scrotal disorders: evaluation of testicular enhancement patterns at dynamic
contrast-enhanced subtraction MR imaging.
AB - PURPOSE: To evaluate testicular enhancement patterns in various scrotal disorders
at dynamic contrast medium-enhanced subtraction magnetic resonance (MR) imaging.
MATERIALS AND METHODS: Forty-two patients with scrotal symptoms (22 testicular
diseases, 20 extratesticular scrotal disorders) underwent three-dimensional (3D)
fast field-echo or fast spin-echo dynamic subtraction MR imaging after injection
of paramagnetic contrast medium. The relative percentages of peak height and mean
slope of the testes on the affected side were compared with those on the
unaffected side by using time-signal intensity curves. RESULTS: Extratesticular
scrotal disorders (time-signal intensity curve mean peak height, 93.1%; mean
slope, 89.8%) showed gradual and progressive increase in homogeneous testicular
contrast enhancement in all normal testes. Relative percentages of peak height
and mean slope of testicular torsion (mean peak height, 17.3%; mean slope,
10.6%), infarction (mean peak height, 30.4%; mean slope, 19.8%), traumatic
hemorrhagic necrosis (mean peak height, -3.5%; mean slope, -12.0%), and
epidermoid cyst (mean peak height, -6.6%; mean slope, -14.2%) were significantly
lower than those of extratesticular scrotal disorders. Acute mumps orchitis (mean
peak height, 135.1%; mean slope, 307.5%) and malignant testicular tumor (mean
peak height, 178.7%; mean slope, 467.6%) showed higher relative percentages of
peak height and mean slope. CONCLUSION: Dynamic contrast-enhanced subtraction MR
imaging can provide information about testicular perfusion on the basis of
contrast enhancement and can be used to differentiate testicular diseases from
scrotal disorders.
PMID- 11012449
TI - Symptomatic fibroleiomyomata: MR imaging of the uterus before and after uterine
arterial embolization.
AB - PURPOSE: To determine the magnetic resonance (MR) imaging features of uterine
fibroleiomyomata after uterine arterial embolization (UAE) and identify
pretreatment MR imaging features that may be predictive of successful UAE.
MATERIALS AND METHODS: T1- and T2-weighted and dynamic gadolinium-enhanced T1
weighted images were obtained before and 3 months after UAE in 31 patients. Up to
five fibroleiomyomata (total of 125) were evaluated for volume, location, signal
intensity characteristics, and vascularity. Region-of-interest curves were used
to assess the vascular enhancement pattern of each fibroleiomyoma and adjacent
myometrium. Each patient completed a questionnaire on symptoms 3 months after
UAE. RESULTS: UAE resulted in significant reductions in mean uterine volume (from
588.6 to 393.1 cm(3)) and mean fibroleiomyoma volume (from 69.4 to 41.4 cm(3)) (P
<.005). After UAE, lesions showed signal intensity changes consistent with
hemorrhagic infarction. The vascularity of fibroleiomyomata was decreased (P
<.001), with no significant change in myometrial vascularity. Submucosal location
was a strong positive predictor of fibroleiomyoma volume reduction (P < 001).
When a reduction in vascularity was the measure of success, hypervascularity was
a strong indicator of success (P <. 005). CONCLUSION: MR imaging is useful for
quantitative assessment of signal intensity and morphologic changes before and
after UAE. Pretreatment MR imaging findings may help predict the success of the
procedure.
PMID- 11012450
TI - Fetal lip and primary palate: three-dimensional versus two-dimensional US.
AB - PURPOSE: To determine if three-dimensional (3D) ultrasonography (US) improves the
ability to define the location and extent of facial clefting prenatally compared
with two-dimensional (2D) US. MATERIALS AND METHODS: Thirty-one fetuses suspected
of having a facial cleft were examined prospectively with 2D and 3D US. Follow-up
was performed in all fetuses. RESULTS: Twenty-eight fetuses had a cleft lip at
birth. The location of the cleft lip was correctly identified in all fetuses with
3D US and in 26 of 28 with 2D US. Twenty-two fetuses had a cleft primary palate.
Nineteen and nine of 22 cleft palates were identified by using 3D and 2D US,
respectively. Three fetuses suspected of having a facial cleft at 2D US had a
normal palate at 3D US and at birth. CONCLUSION: Three-dimensional US is useful
to identify the location and extent of facial clefting. The advantages of 3D US
are the following: (a) The face may be viewed in a standard orientation, (b) the
defect may be viewed systematically by using an interactive display, and (c) the
rendered image provides landmarks for the planar images. Patient decisions may be
affected, since they can view the abnormality on a recognizable 3D rendered
image.
PMID- 11012451
TI - Nonpalpable breast lesions: evaluation with power Doppler US and a microbubble
contrast agent-initial experience.
AB - PURPOSE: To evaluate power Doppler ultrasonography (US) performed with a
microbubble US contrast agent in the differentiation of nonpalpable breast
lesions. MATERIALS AND METHODS: Fifty nonpalpable breast lesions in 50 patients
were prospectively evaluated with power Doppler US before and after injection of
the contrast agent SH U 508A. Lesion vascularity and the morphology of vessels on
US scans were analyzed and were correlated with histologic results. RESULTS:
Surgical excision revealed 22 cancers and 28 benign lesions. At nonenhanced power
Doppler US, eight (36%) of 22 cancers and four (14%) of 28 benign lesions were
vascular. At contrast agent-enhanced power Doppler US, 21 (95%) cancers and six
(21%) benign lesions were vascular (P <.001). Irregular vessels were seen in
three cancers and one benign lesion at nonenhanced power Doppler US and in 11
cancers and one benign lesion at contrast-enhanced power Doppler US. By using the
presence of vascularity in the mass as the diagnostic criterion for malignancy,
the sensitivity, specificity, and positive and negative predictive values of
power Doppler US changed from 36%, 86%, 67%, and 63%, respectively, to 95%, 79%,
78%, and 96% after contrast agent injection. CONCLUSION: Contrast-enhanced power
Doppler US was superior to nonenhanced power Doppler US in the demonstration and
characterization of tumor vascularity in nonpalpable breast lesions. Contrast
enhanced power Doppler US may be useful for the differentiation between
nonpalpable breast cancers and benign tumors.
PMID- 11012452
TI - New bilateral microcalcifications at mammography in a postlactational woman: case
report.
AB - A 33-year-old woman with a strong family history of breast cancer who was
referred for mammography 5 weeks after completing lactation was found to have new
diffuse bilateral microcalcifications in the breast ducts. Contrast material
enhanced magnetic resonance imaging of the breast showed bilateral patchy areas
of abnormal enhancement. Large-core needle biopsy showed diffuse calcifications
within expanded benign ducts in a background of lactational change, without
evidence of malignancy. To the authors' knowledge, these calcifications have not
been previously reported and are possibly related to milk stasis or apoptosis
associated with lactation.
PMID- 11012453
TI - Small pulmonary nodules: volumetrically determined growth rates based on CT
evaluation.
AB - PURPOSE: To determine the accuracy of high-resolution computed tomographic (CT)
volumetric measurements of small pulmonary nodules to assess growth and
malignancy status. MATERIALS AND METHODS: The accuracy of three-dimensional (3D)
image extraction and isotropic resampling techniques was assessed by performing
three experiments. The first experiment measured volumes in spherical synthetic
nodules of two diameters (3.20 and 3.96 mm), the second measured deformable
silicone synthetic nodules prior to and after their shape had been altered
markedly, and the third measured nodules of various shapes and sizes. Three
dimensional techniques were used to assess growth in 13 patients for whom the
final diagnosis was known and whose initial nodule diameters were less than 10
mm. By using the exponential growth model and the calculated nodule volume at two
points in time, the doubling time for each subject was calculated. RESULTS: The
three synthetic nodule studies revealed that the volume could be measured
accurately to within +/-3%. All five malignant nodules grew, and all had doubling
times less than 177 days. Some malignant nodules had asymmetric patterns of
growth identified by using the 3D techniques but not the two-dimensional methods.
All eight benign nodules had doubling times of 396 days or greater or showed a
decrease in volume. CONCLUSION: CT volumetric measurements are highly accurate
for determining volume and are useful in assessing growth of small nodules and
calculating their doubling times.
PMID- 11012454
TI - Solitary pulmonary nodules in patients with extrapulmonary neoplasms.
AB - PURPOSE: To determine the frequency of single lung metastasis, primary lung
cancer, and benign lesions in patients with a solitary lung nodule and a primary
extrapulmonary neoplasm. MATERIALS AND METHODS: The authors evaluated the
electronic charts of 149 patients with an extrapulmonary malignant neoplasm and a
solitary pulmonary nodule. The histologic characteristics of the nodule were
correlated with those of the extrapulmonary neoplasm and with patient age and
smoking history. RESULTS: Patients with carcinomas of the head and neck, bladder,
breast, cervix, bile ducts, esophagus, ovary, prostate, or stomach were more
likely to have primary bronchogenic carcinoma than lung metastasis (ratio, 25:3
for patients with head and neck cancers; 26:8 for patients with other types of
cancer combined). Patients with carcinomas of the salivary glands, adrenal gland,
colon, parotid gland, kidney, thyroid gland, thymus, or uterus had fairly even
odds (ratio, 13:16). Patients with melanoma, sarcoma, or testicular carcinoma
were more likely to have a solitary metastasis than a bronchogenic carcinoma
(ratio, 23:9). Thirty patients had a benign nodule. There was substantial overlap
in age distribution among the patients with benign disease, lung cancer, and
metastasis, although no patient younger than 44 years had a lung cancer. Smokers
had a 3.5-fold higher chance of developing lung cancer compared with nonsmokers.
CONCLUSION: The likelihood of a primary lung cancer versus a metastasis depends
on the histologic characteristics of the extrapulmonary neoplasm and the
patient's smoking history.
PMID- 11012455
TI - Infectious pseudoaneurysms suspected at echocardiography: electron-beam CT
findings.
AB - PURPOSE: To review the electron-beam computed tomographic (CT) findings in
patients with clinical endocarditis and suspected of having perivalvular
pseudoaneurysms at echocardiography and to compare these findings with
echocardiographic data. MATERIALS AND METHODS: Data on 17 patients who underwent
electron-beam CT for suspicion of perivalvular infectious pseudoaneurysm at
echocardiography were retrospectively reviewed. Thirteen patients had a history
of valvular surgery. Electron-beam CT findings-lesion size, number, extent, and
relationships with surrounding structures, and associated lesions-were compared
with echocardiographic and surgical and/or autopsy data. RESULTS: In all
patients, electron-beam CT depicted one or more abnormal cavities that filled
with contrast material after bolus injection. The mean size (3.5 cm) and number
(n = 21) of pseudoaneurysms recorded with electron-beam CT were greater than
those recorded with echocardiography (2.9 cm and n = 13, respectively).
Associated electron-beam CT findings included valvular vegetations in three
patients; mediastinitis in two; and coronary arterial involvement in six. In
eight (47%) patients, electron-beam CT depicted a pseudoaneurysm or an additional
pseudoaneurysm that was only suspected-not depicted-at echocardiography.
Transthoracic and transesophageal echocardiography resulted in underestimation of
lesion number, size, and extent and associated lesions, particularly in patients
with valvular prostheses or voluminous lesions. CONCLUSION: Thoracic infectious
pseudoaneurysms are well depicted with electron-beam CT, which may be a useful
addition to echocardiography for detection of this disease and thus help in
preoperative planning.
PMID- 11012456
TI - MR coronary angiography with breath-hold targeted volumes: preliminary clinical
results.
AB - PURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary
angiography strategy involving a small targeted volume to image one coronary
segment in a single breath hold for the detection of greater than 50% stenosis.
MATERIALS AND METHODS: Thirty-eight patients referred for elective coronary
angiography were included. The coronary arteries were localized during single
breath-hold, three-dimensional imaging of the entire heart. MR coronary
angiography was then performed along the major coronary branches with a double
oblique, three-dimensional, gradient-echo sequence. Conventional coronary
angiography was the reference-standard method. RESULTS: Adequate visualization
was achieved with MR coronary angiography in 85%-91% of the proximal coronary
arterial branches and in 38%-76% of the middle and distal branches. Overall, 187
(69%) of 272 segments were suitable for comparison between conventional and MR
coronary angiography. The diagnostic accuracy of MR coronary angiography for the
detection of hemodynamically significant stenoses was 92%; sensitivity, 68%; and
specificity, 97%. The sensitivity in individual segments was 50%-77%, whereas the
specificity was 94%-100%. CONCLUSION: Adequate visualization of the major
coronary arterial branches was possible in the majority of patients. The observed
accuracy of MR coronary angiography for detection of hemodynamically significant
coronary arterial stenosis is promising, but it needs to be higher before this
modality can be used reliably in a clinical setting.
PMID- 11012457
TI - Coronary artery bypass grafts: improved electron-beam tomography by prolonging
breath holds with preoxygenation.
AB - In 45 patients with coronary bypass grafts, the breath-hold interval with and
that without preoxygenation was measured. Its effect on depiction of the distal
graft anastomosis at electron-beam tomography was evaluated. Preoxygenation
prolonged the breath-hold interval in most patients, thereby allowing greater
anatomic coverage including more distal anastomoses. Preoxygenation may improve
scanning of coronary bypass grafts and increase detectability of graft stenoses.
PMID- 11012458
TI - Contrast-enhanced 3D MR angiography with simultaneous acquisition of spatial
harmonics: A pilot study.
AB - A partially parallel image acquisition technique, simultaneous acquisition of
spatial harmonics, or SMASH, was used to increase the spatial and/or temporal
resolution in contrast material-enhanced three-dimensional magnetic resonance
angiography of the abdominal aorta and renal arteries. In eight healthy subjects,
the breath-hold duration was halved at constant spatial resolution, or the
spatial resolution was doubled at fixed breath-hold duration, with a 30%-55%
reduction in the signal-to-noise ratio but otherwise preserved or improved image
quality.
PMID- 11012459
TI - Real-time projection MR angiography: feasibility study.
AB - Intraarterial injections of small doses of gadopentetate dimeglumine were
combined with a fast spoiled-gradient-echo magnetic resonance (MR) sequence to
obtain real-time projection angiographic images of the rabbit aorta and canine
coronary arteries. Arterial filling and washout, as well as venous and perfusion
phases, were clearly displayed, demonstrating that arterial fluoroscopy in which
an MR technique is used is feasible.
PMID- 11012460
TI - Proton MR spectroscopic imaging without water suppression.
AB - To improve reproducibility in proton magnetic resonance (MR) spectroscopic
imaging in human brain, simultaneous acquisition of the internal water reference
and metabolite signals was evaluated. Measurements in healthy volunteers showed
that the increase in dynamic range from signal oversampling was sufficient to
avoid digitization errors. In addition, use of singular value decomposition
techniques and finite impulse response filters proved effective in separating
water and metabolite signals and providing estimates of the metabolite
concentrations.
PMID- 11012461
TI - MR imaging of acute cervical spine injuries.
PMID- 11012462
TI - Academic degrees in the United States and abroad.
PMID- 11012464
TI - In memoriam
PMID- 11012463
TI - Follow-up of probably benign breast lesions.
PMID- 11012465
TI - In memoriam
PMID- 11012466
TI - Abstracts of current literature
PMID- 11012467
TI - Review article: gastrin and colorectal cancer.
AB - The polypeptide hormone gastrin was identified nearly a hundred years ago and its
role in the regulation of acid secretion is well established. Gastrin also acts
as a growth factor and is trophic for the normal gastric oxyntic mucosa. This
growth promoting action has led to the extensive investigation of its role in
carcinogenesis, in particular colorectal neoplasia. The relationship between
gastrin and colorectal adenocarcinoma has been subject to controversy, however
the findings from several recent studies have resulted in a clearer understanding
of the mechanism of action of gastrin in this is common cancer. The majority of
colorectal cancers produce their own gastrin, which may act in an autocrine
manner. The tumour cells also express gastrin/CCKB receptors (and/or a
combination of isoforms) which mediate the proliferative action. This locally
produced gastrin gives rise to a small increase in systemic gastrin levels.
Autocrine gastrin may also have a role in tumour development, as expression
occurs early in the adenoma-carcinoma sequence. In addition, several studies
using animal models have shown that systemic hypergastrinaemia promotes the
proliferation of both normal and neoplastic colonic epithelium.
Hyperproliferative colonic epithelium in the presence of hypergastrinaemia has
been recorded in humans and a well-designed epidemiological study has
demonstrated an increased incidence of colorectal cancer. Gastrin is a potential
therapeutic target in the treatment of colorectal cancer and several approaches
have been assessed. Receptor antagonists and antisecretory agents have been
demonstrated to be ineffectual. Novel methods of inhibition, including the use of
anti-gastrin antibodies, are currently being evaluated.
PMID- 11012468
TI - Esomeprazole improves healing and symptom resolution as compared with omeprazole
in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole
Study Investigators.
AB - BACKGROUND: The pharmacologic profile of the new proton pump inhibitor
esomeprazole has demonstrated advantages over omeprazole that suggest clinical
benefits for patients with acid-related disease. METHODS: 1960 patients with
endoscopy-confirmed reflux oesophagitis (RO) were randomized to once daily
esomeprazole 40 mg (n=654) or 20 mg (n=656), or omeprazole 20 mg (n=650), the
standard recommended dose for RO, for up to 8 weeks in a US, multicentre, double
blind trial. The primary efficacy variable was the proportion of patients healed
at week 8. Secondary variables included healing and heartburn resolution at week
4, time to first resolution and sustained resolution of heartburn, and per cent
of heartburn-free days and nights. Safety and tolerability were also evaluated.
RESULTS: Significantly more patients were healed at week 8 with esomeprazole 40
mg (94.1%) and 20 mg (89.9%) vs. omeprazole 20 mg (86.9%), using cumulative life
table estimates, ITT analysis (each P < 0.05). Esomeprazole 40 mg was also
significantly more effective than omeprazole for healing at week 4 and for all
secondary variables evaluating heartburn resolution. The most common adverse
events in all treatment groups were headache, abdominal pain and diarrhoea.
CONCLUSION: Esomeprazole was more effective than omeprazole in healing and
symptom resolution in GERD patients with reflux oesophagitis, and had a
tolerability profile comparable to that of omeprazole.
PMID- 11012469
TI - CYP2C19 genotype status and intragastric pH during dosing with lansoprazole or
rabeprazole.
AB - BACKGROUND: CYP2C19 has an important role in the catabolism of several proton
pump inhibitors. However, the relative contribution of CYP2C19-mediated
metabolism varies among the different proton pump inhibitors. AIM: To determine
the effect of CYP2C19 genotype status on intragastric pH during dosing with
lansoprazole or rabeprazole. SUBJECTS AND METHODS: The subjects were 20 male
volunteers without Helicobacter pylori infection. Their CYP2C19 genotype status
was determined by a polymerase chain reaction-restriction fragment length
polymorphism method. Twenty-four-hour monitoring of intragastric acidity was
performed three times: once without medication, once on the last day of a 7-day
course of rabeprazole, and once on the last day of a 7-day course of
lansoprazole. RESULTS: Subjects were divided into three groups on the basis of
their CYP2C19 genotype status: homozygous extensive metabolizers (homo-EMs, n=7),
heterozygous extensive metabolizers (hetero-EMs, n=9), and poor metabolizers
(PMs, n=4). The median pH during rabeprazole administration was not influenced by
CYP2C19 genotype. On the other hand, the median pH in PMs during lansoprazole
dosing was higher than in homo-EMs and hetero-EMs. The percentage of time with pH
< 4.0 had a similar tendency to that of median pH. CONCLUSION: CYP2C19 genotype
status influences gastric acid suppression by lansoprazole, but not by
rabeprazole.
PMID- 11012470
TI - Proton pump inhibitors: better acid suppression when taken before a meal than
without a meal.
AB - BACKGROUND: Proton pump inhibitors including omeprazole and lansoprazole inhibit
gastric acid secretion by selectively and non-competitively inactivating the H+,
K+ ATPase molecules of the parietal cell, but possibly only those that are
actively secreting acid. This might imply that stimulation of acid secretion by a
meal is necessary for optimal inhibition of gastric secretion. AIM: To quantify
and compare the effect on daytime gastric acidity of omeprazole 20 mg or
lansoprazole 30 mg daily taken 15 min before breakfast, with that of the same
drug taken without a meal. METHODS: Twenty-one healthy volunteers were randomized
to receive either omeprazole or lansoprazole. They were given the drug for two
separate periods of 7 days in randomized order and at least 7 days apart. During
one period the study medication was taken before breakfast; during the other it
was taken at the same hour, but with no meal until 12:00 hours. Lunch was
standardized. On day 7, intragastric pH-metry was performed, starting at 08:00
hours. Tracings were analysed for the 8-h period from 08:00 hours until 16:00
hours with regard to percentage time for which gastric pH was below 4.0 and 3.0,
and median gastric pH. Tracings were also analysed after removing the 1 h
breakfast period, to exclude the buffering effect of the meal. RESULTS: When
taking the drug with breakfast, the median percentage time for which gastric pH <
4.0 was 17.2 (interquartile range 4.6-45.5), compared with 42.0 (interquartile
range 31.4-48.8) when taken without food (P=0.01). Fifteen subjects had better
control of gastric acidity when the medication was taken with breakfast. A pH
threshold of 3 and median pH showed similar differences. When the breakfast
period was removed, the differences were no longer statistically significant.
CONCLUSIONS: When therapy with omeprazole or lansoprazole is indicated,
medication should be taken before a meal for optimal control of daytime gastric
acidity.
PMID- 11012471
TI - A randomized trial of polyurethane and silicone percutaneous endoscopic
gastrostomy catheters.
AB - BACKGROUND: No data are available on differences in complication rate and long
term functioning between polyurethane and silicone percutaneous endoscopic
gastrostomy (PEG) catheters. METHODS: We randomized patients who qualified for
PEG placement to receive either a polyurethane or silicone PEG catheter. Patients
were prospectively monitored for 28 days after placement for the occurrence of
complications. Data on long-term PEG survival were obtained retrospectively from
the Hospital and general practitioner's medical records. RESULTS: One hundred and
six patients were randomized (polyurethane 50, silicone 56). During the first
four weeks of follow-up, major complications occurred twice with both
polyurethane and silicone PEGs (relative risk 1.1, 95% confidence interval: 0.11
11). Overall complications occurred four times with polyurethane and 17 times
with silicone PEGs (relative risk 3.8, 95% confidence interval: 1.37-10.5). Long
term follow-up was available in 96 patients. Seven polyurethane PEGs and 10
silicone PEGs were removed because of PEG malfunctioning, the remainder
functioned well until death or the reinstitution of oral feeding. The median
complication-free survival was 916 days for the polyurethane PEG and 354 days for
the silicone PEG (Log rank test: P=0.24). CONCLUSION: Polyurethane PEG catheters
were associated with less short-term complications than silicone catheters, but
major complications and long-term function were comparable.
PMID- 11012473
TI - Abnormal contractile properties of rectal smooth muscle in chronic ulcerative
colitis.
AB - BACKGROUND: Patients with ulcerative colitis have abnormal rectal motility. AIM:
To compare the contractile properties of rectal smooth muscle from patients with
ulcerative colitis and controls. METHODS: Rectal smooth muscle strips from
patients undergoing resection for ulcerative colitis or cancer (control) were
mounted in an organ bath. The effects of carbachol (receptor-mediated) and
potassium (causes membrane depolarization) were studied. Acetylcholinesterase
histochemistry was performed and nerve counts compared. RESULTS: Ulcerative
colitis (n=41) and control (n=34) strips contracted in response to potassium and
carbachol. Mean (S.E. M.) maximum response to potassium in the control and
ulcerative colitis groups was 1.07 (0.06) g/mg and 1.02 (0.09) g/mg tissue,
respectively (P=N.S.). EC50s (concentrations required to give 50% of maximal
response) were 75 (1) mM and 73 (1) mM, respectively (P=N.S. ). Although maximum
responses to carbachol were similar, 2.12 (0.12) g/mg and 1.95 (0.12) g/mg tissue
(P=N.S.), ulcerative colitis strips exhibited an increased sensitivity to
carbachol, EC50s: 5.05 x 10-6 (0.55 x 10-6) M vs. 8.36 x 10-6 (0.88 x 10-6) M,
P=0.002). There was no significant difference in nerve counts between the
tissues, as assessed by staining for acetylcholinesterase. CONCLUSIONS:
Ulcerative colitis tissue has an increased sensitivity to carbachol and this is
not due to denervation; it may result from increased calcium release from
intracellular stores since contraction due to membrane depolarization is not
altered. Modulation of this pathway could potentially be used to alter rectal
motility in patients with ulcerative colitis.
PMID- 11012472
TI - Impaired contractile response of mesenteric arteries in Crohn's disease.
AB - BACKGROUND: Crohn's disease is associated with vascular injury and dysregulation
of the intestinal immune system which together can provide disturbance of
mesenteric circulation functional properties. AIM: To evaluate the vascular
reactivity of mesenteric arteries from patients with Crohn's disease. METHODS:
Phenylephrine-induced contractions were assessed from 10 patients with Crohn's
disease and 8 control organ donors. NG-nitro-L-arginine-methyl-ester (L-NAME) was
used to test the presence of inducible NO synthase. Endothelium dependent and
independent relaxation was assessed using acetylcholine, bradykinin, calcium
ionophore A23187 and sodium nitroprusside. RESULTS: The contractile response to
phenylephrine was significantly decreased in arteries without endothelium from
patients with Crohn's disease. Exposure to the NO synthase inhibitor L-NAME
restored the contractile response to phenylephrine. Relaxation remained unaltered
in both groups. CONCLUSION: These data provide direct evidence for fading of
contraction caused by phenylephrine in Crohn's disease. The restored mesenteric
artery tone by a specific NO synthase inhibitor suggests that an increased
production for NO in vascular smooth muscle might be responsible of this altered
vascular reactivity.
PMID- 11012474
TI - Low serum retinol levels are associated with hepatocellular carcinoma in patients
with chronic liver disease.
AB - BACKGROUND: Retinol and other vitamin A derivatives affect the differentiation
and growth of many tissues and have anti-tumour properties. AIM: To investigate
serum retinol levels in patients with liver disease and hepatocellular carcinoma
(HCC) and to assess its importance as a risk factor for the development of HCC.
METHODS: Serum retinol levels were measured in healthy volunteers and 175
patients (34 with chronic hepatitis C, 117 with cirrhosis, and 24 with HCC.
RESULTS: The serum retinol levels (mean +/- s.e.) in ng/mL, were 972.1 +/- 37.7
in the control group and 647 +/- 41.1 in patients with chronic hepatitis C. Serum
retinol levels in patients with cirrhosis and HCC were lower than in patients
with cirrhosis alone (365.8 +/- 43.1 vs. 438.9 +/- 22.1, P < 0.04). In
particular, there was a more significant difference in serum retinol levels
between Child-Pugh grade A patients with cirrhosis and Child-Pugh grade A
patients with cirrhosis/HCC (serum retinol levels 532.4 +/- 26.7 vs. 366.1 +/-
86.4, P < 0.03). There was a significant difference in serum retinol levels
between normal controls and all patients' groups (P < 0.001). There were
significantly lower serum retinol levels in cholestatic Child-Pugh grade A
patients with cirrhosis compared with noncholestatic Child-Pugh grade A patients
with cirrhosis/HCC (411.5 +/- 30.3 vs. 579.7 +/- 32.7, P < 0.0004). Sixty percent
of patients with Child-Pugh grade A cirrhosis/HCC had serum retinol levels below
350 ng/mL compared with only 18.4% of cirrhotics without HCC (chi 2-test,
P=0.01). No correlation was found between serum retinol levels and alpha FP or
any other liver function tests, apart from serum albumin, which showed a positive
correlation (r=0.61 P < 0.018). CONCLUSIONS: There was a progressive reduction in
serum retinol levels from controls to patients with liver cirrhosis. Those
patients with cirrhosis and HCC had significantly lower values than patients with
cirrhosis alone. Serum retinol levels may be a risk factor for the development of
HCC.
PMID- 11012475
TI - Ascorbic acid and intestinal metaplasia in the stomach: a prospective, randomized
study.
AB - BACKGROUND: Intestinal type metaplasia plays a role in intestinal type gastric
carcinoma development. Ascorbic acid demonstrates a protective effect against
gastric carcinogenesis, due to its ability to inactivate oxygen free-radicals as
well as its nitrite-scavenging effects. AIM: To assess whether long-term ascorbic
acid administration following Helicobacter pylori eradication could affect
intestinal metaplasia regression in the stomach. METHODS: Sixty-five patients
were included in the study. The inclusion criterion was the presence of
intestinal metaplasia on the gastric mucosa after H. pylori eradication. An upper
gastrointestinal endoscopy was performed and 3 biopsy specimens were taken in the
antrum, 3 in the gastric body, and 2 in the incisura angularis. Patients were
randomized to receive 500 mg of ascorbic acid o.d., after lunch (32 patients) for
6 months or no treatment (33 patients). All patients underwent to endoscopic
control at the end of the 6 months. RESULTS: H. pylori infection recurrence was
detected in 6 (9.4%) patients (three from each group), and these patients were
excluded from further analysis. We were unable to find evidence of intestinal
metaplasia in any biopsied site of the gastric mucosa in 9/29 (31%) patients from
the ascorbic acid group and in 1/29 (3.4%) of the patients from the control group
(P=0.006). Moreover, a further six (20.7%) patients from the ascorbic acid group
presenting chronic inactive pangastritis with widespread intestinal metaplasia at
entry, showed less extensive antritis with intestinal metaplasia at control,
whilst a similar finding was only seen in one patient from the control group
(P=0.051). CONCLUSION: The administration of ascorbic acid significantly helps to
resolve intestinal metaplasia of the gastric mucosa following H. pylori
eradication, and its use as a chemoprevention treatment should be considered.
PMID- 11012476
TI - Helicobacter pylori-gastrin link in MALT lymphoma.
AB - BACKGROUND: There is accumulating evidence for the role of Helicobacter pylori in
the development of gastric cancer as well as of lymphomas that arise in mucosa
associated lymphoid tissue (MALT). We reported recently that gastric cancer
patients show high prevalence of cagA-positive H. pylori and express gastrin and
gastrin receptors enabling them to stimulate tumour growth in autocrine fashion.
AIMS: Since the H. pylori infection is considered to be more strongly associated
with MALT lymphoma than with gastric cancer, we decided to determine the gastrin
and its receptors' mRNA expression and gastrin content in this tumour as well as
the release of this hormone both into plasma and gastric lumen. Twenty MALT
lymphoma patients were compared with 100 age- and gender-matched controls with
similar dyspeptic symptoms. RESULTS: The overall H. pylori seropositivity in MALT
lymphoma was about 90% and CagA positivity was 70%, compared to 56% and 33%,
respectively, in controls. The serum gastrin in MALT lymphoma was about sixfold
higher than in controls while gastric luminal gastrin in these patients was over
70 times higher than in controls. Gastrin content in tumour was about 10-fold
higher than in antral mucosa. Gastrin and gastrin-receptor (CCKB-receptor) mRNA
were detected by reverse transcriptase-polymerase chain reaction in cancer tissue
whilst in the fundic and antral mucosa, only enhanced expression of CCKB-receptor
mRNA and gastrin mRNA was detected, respectively. Histamine stimulation in MALT
lymphoma induced acid secretion that was only about 30% of control value due to
atrophic gastritis. This study confirms an important role of CagA-positive H.
pylori in the pathogenesis of MALT lymphoma and shows that this lymphoma is
capable of synthesizing and releasing potent growth promoting gastrin, possibly
due to the action on G-cells of H. pylori-originated Nalpha-methyl histamine and
cytokines (tumour necrosis factor alpha and interleukin-8). CONCLUSIONS: Gastric
MALT lymphoma is closely linked to CagA-positive H. pylori infection. Gastrin and
its receptors may be implicated in the pathogenesis of gastric lymphoma.
PMID- 11012477
TI - Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a
meta-analysis of eradication of Helicobacter pylori.
AB - AIM: To perform a meta-analysis of studies comparing twice daily, one-week triple
therapy with a proton pump inhibitor, clarithromycin (C) and amoxycillin (A)
(PCA) vs. those using proton pump inhibitor, clarithromycin and a nitroimidazole
(N) (PCN) for H. pylori eradication. REVIEW METHODS: SELECTION CRITERIA:
Comparative randomized trials of PCA vs. PCN were included. DATA SOURCES: PubMed
database and abstracts from congresses until September 1999. STATISTICS: Meta
analysis was performed combining the Odds Ratios (OR) of the individual studies
in a global OR (Peto method) both on an intention-to-treat (ITT) and on a per
protocol (PP) basis. RESULTS: Twenty-two studies fulfilled the inclusion
criteria. Eighteen studies reported ITT and 20 PP analysis. Mean H. pylori
eradication rates were 81% (95% CI: 79-83%) ITT, and 84% (82-86%) PP with PCA,
and 81% (78-83%) ITT and 84% (82-86%) PP with PCN; the odds ratio for the effect
of PCA vs. PCN was 1 (0.83-1.22) on an ITT, and 0.98 (0.8-1.2) on a PP basis.
Subanalysis showed that mean H. pylori eradication efficacy with PC(250 b.d.)A
was 81% (78-85%) ITT, vs. 86% (83-89%) with PC(250 b.d.)N. The odds ratio for
this comparison was 0.68 (0.48-0.98). Finally, when comparing PC(500 b.d. )A
against PC(250 b.d.)N ITT cure rates were 77% (74-80%), and 75% (72-78%) with an
odds ratio of 1.18 (0.93-1.5). CONCLUSION: Overall, one-week combination regimens
of PCA and PCN present similar H. pylori eradication efficacy. Nevertheless, the
PCN regimen obtains significantly better results when using low doses of C (250
mg b.d.).
PMID- 11012478
TI - Helicobacter pylori-positive duodenal ulcer: three-day antibiotic eradication
regimen.
AB - BACKGROUND: The most widely used treatments for ulcer healing and Helicobacter
pylori eradication consist of a 1-2 week regimen of a proton pump inhibitor plus
two or three antimicrobials. AIMS: To evaluate the efficacy, safety, cost, and
tolerance of a three-day regimen with three antibiotics vs. a 10-day treatment
with a proton pump inhibitor or vs. a ranitidine bismuth citrate triple therapy.
METHODS: Two hundred and twenty-one patients with endoscopically-proven H. pylori
positive duodenal ulcers were recruited to the study. Recruited patients were
assigned to one of the following four regimens: (I) omeprazole 40 mg o.m. plus
amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. for 10 days (OAC: 55
patients); (ii) omeprazole 40 mg o.m. on days 1-5, plus amoxycillin 1 g b.d.,
clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. on days 3-5 (OACM: 56
patients); (iii) ranitidine bismuth citrate 400 mg b.d. plus amoxycillin 1 g b.d.
and clarithromycin 500 mg b.d. for 10 days (RAC: 54 patients); (iv) ranitidine
bismuth citrate 400 mg b.d. on days 1-5, plus amoxycillin 1 g b.d.,
clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. on days 3-5 (RACM: 56
patients). Fisher's exact test was used to compare data regarding healing and
eradication in the four groups. RESULTS: The intention-to-treat eradication and
ulcer healing rates for the RACM regimen were 95% and 98%, respectively.
Statistically significant differences were observed, relating to the eradication
and healing of ulcers, between RACM and either the RAC or OAC regimens.
CONCLUSION: The three-day antibiotic therapy with amoxycillin, clarithromycin and
metronidazole in addition to ranitidine bismuth citrate is a very effective anti
H. pylori regimen.
PMID- 11012479
TI - Third line treatment for Helicobacter pylori: a prospective, culture-guided study
in peptic ulcer patients.
AB - BACKGROUND: A third line treatment is needed in roughly 5% of patients infected
with Helicobacter pylori. Few data have been reported on efficacy of treatment
regimens in these patients. METHODS: A prospective trial was designed to study
the effectiveness of third line treatment of H. pylori infection in ulcer
patients. Two-week quadruple, culture-guided, combinations were used in 31
consecutive patients. Susceptibility to metronidazole and clarithromycin were
studied by E-test, and thereafter a predetermined treatment regimen was used.
Compliance was evaluated by pill count, and eradication defined by negative urea
breath test at 6 weeks. RESULTS: Two main quadruple regimens were used in 29
patients. In spite of good compliance, the combination of omeprazole,
tetracycline, bismuth and clarithromycin (OTBC) showed an eradication rate (per
protocol analysis) of 36% (five out of 14; CI: 12.8-64.9), and if amoxycillin was
used (OTBA) the rate was 67% (eight out of 12; CI: 34.9-90.1). The difference was
not significant. No clinical factor was found to be associated with failure to
eradicate. CONCLUSIONS: Third line treatment often fails to eradicate H. pylori
infection. New strategies need to be developed and tested for this common
clinical situation.
PMID- 11012480
TI - Efficacy of two one-week rabeprazole/levofloxacin-based triple therapies for
Helicobacter pylori infection.
AB - BACKGROUND: One-week low-dose proton pump inhibitor-based triple therapies have
usually proved to be effective treatments for Helicobacter pylori infection. AIM:
To investigate the eradication efficacy, safety profile and patient compliance of
two triple therapies containing a standard dose of rabeprazole and a new
fluoroquinolone, levofloxacin. METHODS: One hundred patients referred to us for
gastroscopy, who were H. pylori-positive, were consecutively recruited in a
prospective, open-label study. The enrolled patients were randomised to receive a
seven-day course of rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and
either amoxycillin 1 g b.d. (RLA group) or tinidazole 500 mg b.d. (RLT group).
Their H. pylori status was assessed by means of histology and rapid urease test
at entry, and by 13C-urea breath test 8 weeks after the end of treatment.
RESULTS: All 100 enrolled patients completed the study. Forty-six of 50 patients
treated with RLA (both PP and ITT analysis: 92%; 95% CI: 81-98%) and 45 of 50
with RLT (both PP and ITT analysis: 90%: 95% CI: 78-97%), became H. pylori
negative. Slight or mild side-effects occurred in 4 (8%) patients of the RLA
group and in 5 (10%) of the RLT group. CONCLUSIONS: This study demonstrates the
efficacy of two 1-week rabeprazole-based triple therapies including levofloxacin
to eradicate H. pylori. These regimens prove to be safe, well-tolerated, and
achieved good eradication rates. Levofloxacin may be an effective alternative to
clarithromycin in triple therapy regimens.
PMID- 11012481
TI - Changes in Helicobacter pylori-induced gastritis in the antrum and corpus during
long-term acid-suppressive treatment in Japan.
AB - BACKGROUND: Several studies have shown that acid-suppressive therapy aggravates
corpus gastritis in patients with Helicobacter pylori infection, promoting the
development of atrophic gastritis. AIM: To study the effects of long-term use of
antisecretory agents on the H. pylori-positive gastric mucosa in Japan, a country
with a high incidence of gastric cancer. METHODS: A total of 141 H. pylori
positive patients who had peptic ulcers or reflux oesophagitis were treated for 3
years with either omeprazole (20 mg/day) alone (n=7) or with omeprazole for
primary therapy (8 weeks), followed by famotidine (40 mg/day) for maintenance
therapy (n=134). Endoscopy was performed before, during, and after treatment.
Biopsy specimens were taken from the greater curvature of the antrum and corpus
and were examined histologically. RESULTS: The long-term use of famotidine after
8 weeks of treatment with omeprazole distinctly decreased H. pylori density and
neutrophil infiltration in the antrum, but did not change H. pylori density in
the corpus. The gastritis score increased in patients who had no, or only mild
corpus gastritis before treatment (n=74), and significantly decreased in those
who had moderate or severe gastritis before treatment (n=60). In four of the
seven patients who received long-term treatment with omeprazole alone, neutrophil
infiltration and H. pylori density decreased not only in the antrum but also in
the corpus. There was no increase in intestinal metaplasia or mucosal atrophy as
assessed endoscopically during follow-up. CONCLUSION: Changes in corpus gastritis
in response to acid-suppressive therapy depend on the severity of gastritis
before treatment. Long-term use of acid-suppressive therapy apparently does not
accelerate the development of atrophy or intestinal metaplasia in Japanese
patients.
PMID- 11012482
TI - (13)C-urea breath test without a test meal is highly accurate for the detection
of Helicobacter pylori infection in Chinese.
AB - BACKGROUND: Conventional (13)C-urea breath testing ((13)C-UBT) includes a test
meal to delay gastric emptying, which, theoretically, improves the accuracy of
the test. Citric acid has been proposed as the best test meal. However, recent
studies have suggested that a test meal may not be necessary. AIM: To investigate
a new (13)C-UBT protocol without a test meal in a Chinese population. METHODS:
Consecutive dyspeptic patients referred for upper endoscopy were recruited. (13)C
UBT was performed on two separate days with or without a test meal (2.4 Gm citric
acid) and compared with the 'gold standard' (CLO test and histology). RESULTS:
Two hundred and two patients were tested. Using receiver operating
characteristics (ROC) analysis, the optimal delta-value and optimal measurement
interval for UBT were 5% and 30 min, respectively, both with or without a test
meal. The sensitivity, specificity, positive predictive value, negative
predictive value and accuracy of (13)C-UBT with citric acid (96.5%, 97.7%, 98.2%,
95.6%, 97.0%) were similar to (13)C-UBT without a test meal (94.7%, 97.7%, 98.2%,
93.5%, 96.0%). CONCLUSION: This simplified (13)C-UBT protocol without a test meal
produced highly accurate and reliable results in the Chinese population.
PMID- 11012483
TI - Lower-dose (13)C-urea breath test to detect Helicobacter pylori infection
comparison between infrared spectrometer and mass spectrometry analysis.
AB - BACKGROUND: The expense of the (13)C-urea breath test (UBT) to detect
Helicobacter pylori infection is mainly due to the cost of (13)C-urea and the
analysis using isotope ratio mass spectrometry (IRMS). AIM: To test whether a
UBT, using a lower dose of urea and lower-priced isotope-selective nondispersive
infrared spectrometry (INIS), can preserve diagnostic efficacy in clinical
practice. METHODS: A total of 177 dyspeptic patients received endoscopy for H.
pylori culture and histology. All of them received a UBT in which the duplicate
baseline, 10 min, and 15 min breath samples after ingestion of 50 mg (13)C-urea
were collected to analyse the excess (13)CO(2)/(12)CO(2) ratio (ECR) by IRMS
(ABCA, Europa Scientific, UK) and INIS (UBiT-IR200, Photal Otsuka Electronics,
Japan), respectively. RESULTS: Of the 177 patients, 84 were infected and 93 were
uninfected with H. pylori. A close correlation of ECR was found between IRMS and
INIS (r=0.9829 at 10 min; r=0.9918 at 15 min, P < 0.0001). Analysing the 15-min
samples, UBT by both IRMS and INIS achieved the same sensitivity (96. 4%) and
specificity (98.9%). CONCLUSIONS: INIS is as effective as IRMS for UBT, and can
use a lower dose of (13)C-urea. This can provide an economic UBT, using the lower
priced INIS and a low dose of (13)C-urea.
PMID- 11012484
TI - Gastric acid secretion in cyclooxygenase-1 deficient mice.
AB - BACKGROUND: Constitutive cyclooxygenase-1 enzyme synthesizes prostaglandins which
are thought to play an important role in the functional integrity of the stomach
gastric mucosa. Recently, it was shown that cyclooxygenase-1 deficient mutant
mice did not develop spontaneous gastric pathology and appear less sensitive to
indomethacin-induced gastric damage. AIM: To investigate gastric acid secretion
in cyclooxygenase-1 deficient mutant mice. METHODS: The basal and histamine or
isobutyl methylxanthine-stimulated acid secretion in stomachs of cyclooxygenase-1
deficient homozygous mice and the effect of indomethacin was compared with that
of heterozygous and wild-type mice using isolated lumen perfused mouse stomachs,
in organ baths, monitored by pH-electrodes. RESULTS: There was no significant
difference in the basal or histamine stimulated gastric acid secretion between
wild-type or heterozygous or homozygous mice. However, isobutyl methylxanthine
was more potent in the cyclooxygenase-1 deficient and heterozygous mice than in
wild-type mice. Indomethacin, at concentrations below 1 mM, had no effect on
either basal or histamine stimulated acid secretion in any of the mice
populations. CONCLUSION: Gastric acid secretion is maintained without
prostaglandin involvement in cyclooxygenase-1 deficient mice. The finding that
basal and histamine-stimulated gastric acid secretion was similar in the
cyclooxygenase-1 deficient, compared to wild-type mice is consistent with the
lack of spontaneous gastric pathology in the cyclooxygenase-1 deficient mice.
PMID- 11012485
TI - Local and systemic effects of peritoneal lavage with high concentrations of
adenosine in rats.
AB - BACKGROUND: Adenosine exerts actions which may be beneficial in treating diseases
of the gastrointestinal tract. However, administered systemically, adenosine
causes a 'stress reaction' and may adversely affect blood pressure and cardiac
and renal function. AIM: To determine whether peritoneal lavage with adenosine
provides pharmacological levels of adenosine in the intestines without elevating
adenosine levels in the systemic circulation. METHODS: Rats received an
intramesenteric artery infusion of angiotensin II (30 ng/min) plus methoxamine (3
microg/min) to reduce mesenteric blood flow by approximately 60%, and adenosine
solutions were instilled into the abdominal cavity. In a second study,
microdialysis probes were placed in the mesenteric vein and aortic arch of rats,
and the peritoneal cavity was continuously lavaged with adenosine solutions.
RESULTS: High concentrations (10(-3)M) of adenosine normalized the mesenteric
blood flow without affecting blood pressure or heart rate. High concentrations of
adenosine (10(-3)M) induced micromolar levels of adenosine and inosine in the
mesenteric vein, without affecting adenosine or inosine levels in the aorta.
CONCLUSIONS: Peritoneal lavage with high concentrations of adenosine provides
pharmacological levels of adenosine in the gastrointestinal tract without
systemic side-effects. Peritoneal lavage with high concentrations of adenosine
may be useful for the treatment of a number of diseases of the gastrointestinal
tract.
PMID- 11012486
TI - Anaesthesia, what's in a name? - time for change.
PMID- 11012487
TI - Substance misuse amongst anaesthetists.
PMID- 11012488
TI - Substance misuse amongst anaesthetists in the United Kingdom and Ireland. The
results of a study commissioned by the Association of Anaesthetists of Great
Britain and Ireland.
AB - Three hundred and four departments of anaesthesia in UK and Ireland were sent
questionnaires about alcohol and drug abuse in anaesthetists over the preceding
10-year period. Information was sought on the nature and extent of substance
problems, their presentation and management. The survey achieved a high response
rate of 71.7% and a total of 130 cases were reported, of whom 34.6% were
consultants and 43.2% were trainees. Over 50% of respondents felt a lack of
confidence in dealing with alcohol or drug misuse amongst colleagues. The results
of this survey demonstrate that over one anaesthetist per month has presented
with significant alcohol or drug misuse in the UK and Ireland over the last 10
years. It is important that those with management responsibilities for
departments of anaesthesia are aware that such problems exist and are likely to
impact on the professional ability and health of the affected individual. The
Working Party on Substance Abuse at the Association of Anaesthetists has recently
published guidance in the management of these problems. A case is made for
increasing awareness in this sensitive subject to enable early recognition and
treatment of an anaesthetist who is misusing alcohol and drugs since intervention
can be effective.
PMID- 11012489
TI - Closed loop control of anaesthesia: an assessment of the bispectral index as the
target of control.
AB - We investigated the performance of a closed-loop system for administration of
general anaesthesia, using the bispectral index as a target for control. One
hundred patients undergoing gynaecological or general surgery were studied. In 60
patients, anaesthesia was maintained by intravenous infusion of a
propofol/alfentanil mixture. In 40, an isoflurane/nitrous oxide based technique
was used. For each technique, patients were randomly allocated to receive either
closed-loop or manually controlled administration of the relevant agents
(propofol/alfentanil or isoflurane), with an intra-operative target bispectral
index of 50 in all cases. Closed-loop and manually controlled administration of
anaesthesia resulted in similar intra-operative conditions and initial recovery
characteristics. During maintenance of anaesthesia, cardiovascular and electro
encephalographic variables did not differ between closed-loop and manual control
groups and deviation of bispectral index from the target value was similar. Intra
operative concentrations of propofol, alfentanil and isoflurane were within
normal clinical ranges. Episodes of light anaesthesia were more common in the
closed-loop group for patients receiving propofol/alfentanil anaesthesia and in
the manual group for patients receiving isoflurane/nitrous oxide anaesthesia.
Convenience aside, the closed-loop system showed no clinical advantage over
conventional, manually adjusted techniques of anaesthetic administration.
PMID- 11012490
TI - A comparison of antagonism of rocuronium-induced neuromuscular blockade during
sevoflurane and isoflurane anaesthesia.
AB - Volatile anaesthetic agents potentiate neuromuscular blocking agents and retard
their rate of reversal. We hypothesised that there was a difference in the rate
of reversal of rocuronium-induced neuromuscular blockade based on the selection
of inhalation agent. Thirty-eight patients undergoing elective surgical
procedures received either sevoflurane or isoflurane, by random allocation.
Neuromuscular blockade was induced using rocuronium 0.6 mg.kg-1 followed by
continuous intravenous infusion to maintain 90% suppression of the single twitch
response. Upon completion of surgery, the rocuronium infusion was discontinued,
neostigmine 50 microg.kg-1 and glycopyrrolate 10 microg.kg-1 were administered.
Times from reversal to T1 = 25, 50 and 60% and train-of-four ratio = 0.6 were
recorded. The mean (SD) times to train-of-four ratio = 0.6 in the isoflurane and
sevoflurane groups were 327 (132) and 351 (127) s, respectively. The mean (SD)
times to single twitch response T1 = 25, 50 and 60% in the isoflurane group were
81 (33), 161 (59) and 245 (84) s, respectively, and in the sevoflurane group were
95 (35), 203 (88) and 252 (127) s, respectively. It is concluded that reversal of
rocuronium-induced neuromuscular blockade is similar during isoflurane and
sevoflurane anaesthesia.
PMID- 11012491
TI - Determination of sevoflurane alveolar concentration for tracheal intubation with
remifentanil, and no muscle relaxant.
AB - The sevoflurane alveolar concentration needed for tracheal intubation with
remifentanil was studied in 26 adult patients premedicated with 100 mg
hydroxyzine. Anaesthesia was induced with sevoflurane in oxygen. The
concentration was determined by Dixon's up-and-down method. The first patient was
tested at 4.5%. One minute after obtaining the preselected value, remifentanil 1
microg.kg-1 was injected for 60 s followed by an infusion of 0.25 microg.kg-1.
min-1. Ventilation was then manually assisted for 2 min and tracheal intubation
was attempted. Tracheal intubation conditions and responses to intubation were
noted. Heart rate and mean arterial pressure were recorded before induction,
before remifentanil injection, and before and 3 min after tracheal intubation.
The concentration for acceptable intubating conditions was 2.5 +/- 0.7%. From
logistic regression, ED50 and ED95 were 2.0% (95% CI 1.3-2.5) and 3.2% (95% CI
2.6-5.6), respectively. With sevoflurane 2.5%, heart rate and mean arterial
pressure decreased by 18% and 15%, respectively, after remifentanil
administration and increased slightly after tracheal intubation.
PMID- 11012492
TI - Effects of peribulbar bupivacaine as an adjunct to general anaesthesia on peri
operative outcome following retinal detachment surgery.
AB - Sixty premedicated, ASA physical status I or II patients weighing > 25 kg
scheduled for elective retinal detachment repair were randomly assigned to
receive either peribulbar block with 10 ml of 0.25% bupivacaine (block group) or
intravenous morphine 150 microg.kg-1 (morphine group), prior to the induction of
general anaesthesia (n = 30 in each group). Patients were evaluated for intra
operative oculocardiac reflex, peri-operative pain relief, recovery from
anaesthesia and postoperative nausea and vomiting. Apart from significantly
reducing the incidence of oculocardiac reflex (30% vs. 70%, p = 0.0019),
peribulbar bupivacaine also attenuated the severity of the reflex. Postoperative
pain relief was superior in the block group. More block group patients had the
maximum recovery score in the immediate postoperative period (80% vs. 27%, p < 0.
0001) and they achieved complete recovery significantly faster than the morphine
group (17.3 (14.7) min vs. 66.7 (29.7) min, p < 0.0001). The incidence (40% vs.
77%, p = 0.004) and severity of postoperative nausea and vomiting were
significantly less in the block group. In summary, peribulbar bupivacaine, when
administered together with general anaesthesia, attenuated oculocardiac reflex,
provided comparable intra-operative and superior postoperative analgesia,
resulted in significantly earlier and better recovery from anaesthesia, and
significantly reduced the incidence and severity of postoperative nausea and
vomiting.
PMID- 11012493
TI - Protective effects of plasma replacement fluids on erythrocytes exposed to
mechanical stress.
AB - Haemoglobin release from 40 suspensions of packed red blood cells in modified
fluid gelatin, 4% albumin solution, 6% hydroxyethyl starch and normal saline was
investigated in vitro during circulation with a roller pump from a heart-lung
machine for 120 min at a flow rate of 2.5 l.min-1 at room temperature. The lowest
haemoglobin release was obtained with erythrocytes in modified fluid gelatin,
whereas free haemoglobin concentrations became progressively higher with albumin,
hydroxyethyl starch and normal saline [median free haemoglobin (interquartile
range) after 120 min circulation: gelatin 493 (360-601) mg.l-1, albumin 692 (590
1111) mg.l-1, hydroxyethyl starch 1121 (692-1518) mg.l-1, normal saline 1178 (881
1757) mg.l-1, p < 0.001]. Modified fluid gelatin appears to have potent
erythrocyte protective properties similar to those of albumin. This effect could
decrease mechanical haemolysis during extracorporeal circulation or cell saver
autotransfusion if modified fluid gelatin is used as part of a priming solution
or as an additive in wash solutions.
PMID- 11012494
TI - Peripheral nerve injuries associated with anaesthesia.
AB - Peripheral nerve injuries can occur at any time during the peri-operative period.
The long-term disability that results may have serious consequences for a
patient. The incidence of peri-operative nerve injuries can be reduced by
anaesthetists being aware of their causes and pathophysiology. This review
article aims to explain the incidence, pathophysiology and medicolegal
implications of peri-operative nerve injury and provides suggestions as to how
they may best be avoided.
PMID- 11012495
TI - Supplementary oxygenation with the laryngeal mask airway: a comparison of four
devices.
AB - The provision of supplementary oxygen via the laryngeal mask airway used in the
recovery room is important for patient safety. Several devices have been
described for this purpose, but these studies have not included an accurate
measurement of the most clinically important variable, the end-tidal oxygen
concentration. We constructed an artificial model of spontaneous ventilation to
compare the efficacy and safety of four devices; a circuit filter, a Hudson mask,
the 'T-bag' device and a T-piece. We combined the use of oximetry with a
pneumotachograph to provide a continuous picture of the oxygen delivery
characteristics of the devices at flow rates of 2, 4 and 8 l.min-1. The
performances of the T-bag and the T-piece were superior to those of the filter
and Hudson mask, with end-tidal oxygen concentrations of 46.1%, 45.8% and 35.4%,
34.8%, respectively, at 8 l.min-1. Single point assessments of oxygen delivery,
such as peak inspired oxygen concentration, may overestimate the efficacy of test
devices.
PMID- 11012496
TI - Drawbacks of pushovers.
AB - Some military anaesthetists have started to use the Oxford Miniature Vaporiser in
a pushover configuration with the Triservice anaesthetic apparatus. This
vaporiser performs identically in the pushover and drawover configurations with
the Cape TC 50 ventilator. We tested the Oxford Miniature Vaporiser with three
other ventilators and found variable performance. When used in the pushover
configuration with the Laerdal bag at normal minute volumes, the Oxford Miniature
Vaporiser delivers a higher than set output.
PMID- 11012497
TI - A double-blind randomised comparison of ropivacaine 0.5%, bupivacaine 0.375% -
lidocaine 1% and ropivacaine 0.5% - lidocaine 1% mixtures for cataract surgery.
AB - This study evaluated the efficacy and side-effects of plain ropivacaine compared
with ropivacaine-lidocaine and bupivacaine-lidocaine mixtures for peribulbar
blocks in cataract surgery. Ninety patients were randomly allocated to three
groups and received peribulbar blockade using one of the three solutions. Speed
of onset and quality of blockade were assessed using akinesia, surgical
satisfaction and patient satisfaction. Complications and cardiovascular side
effects were noted. There was a slower onset of akinesia using ropivacaine alone,
although at 10 min after injection all groups were equal in this respect. There
was no difference in surgical or patient satisfaction between the groups. There
were no differences in pain on injection, preblock and postblock blood pressure,
heart rate or oxygen saturation. The optimal time to surgical incision after
peribulbar blockade is not less than 15 min and plain ropivacaine fulfils this
criterion.
PMID- 11012498
TI - The effect of the addition of ropivacaine or bupivacaine upon pruritus induced by
intrathecal fentanyl in labour.
AB - Sixty patients in early labour were randomly allocated to one of three groups.
The control group received intrathecal fentanyl 25 microg, the ropivacaine group
received intrathecal fentanyl 25 microg and ropivacaine 2.5 mg while the
bupivacaine group received intrathecal fentanyl 25 microg and bupivacaine 2.5 mg.
The incidence of pruritus was 100% in controls, compared with 85% in the
ropivacaine group (not significant) and 75% in the bupivacaine group (p = 0.003).
The severity of pruritus was significantly less in the ropivacaine (p = 0.006)
and bupivacaine (p = 0.001) groups. Most patients developed pruritus by 30 min.
Pruritus above the abdomen was not reduced in patients receiving local
anaesthetics. There were no significant differences in the mean pain visual
analogue score, systolic blood pressure, maternal heart rate and upper level of
reduced pin-prick sensation in the first 30 min. Intrathecal ropivacaine and,
more so, intrathecal bupivacaine reduce the incidence and severity of pruritus
from intrathecal fentanyl for labour analgesia.
PMID- 11012499
TI - Reducing red blood cell transfusion in elective surgical patients: the role of
audit and practice guidelines.
AB - In 1996, we prospectively audited peri-operative transfusion practice in elective
surgical patients over a 3-month period. Two-unit transfusions represented 60% of
all transfusions. Haemoglobin was measured infrequently prior to transfusion and
the main 'trigger' for transfusion was an estimated blood loss in excess of 500
ml. Transfusion guidelines that required the haemoglobin level to be measured
immediately before transfusion were introduced. The audit was repeated in 1998;
transfusion 'triggers' and the number of transfusions for the two periods were
compared. In the second audit, the total number of transfusions decreased by 43%.
The mean estimated blood loss associated with a 2-unit transfusion had increased
from 608 (373) ml to 1320 (644) ml (p < 0.01) and the estimated haemoglobin
concentration after transfusion had decreased from 12.4 (1.8) g.dl-1 to 9.9 (2.4)
g.dl-1 (p < 0.01). These results suggest that transfusion guidelines can have a
significant impact on clinical practice.
PMID- 11012500
TI - The incidence of transient neurological symptoms after spinal anaesthesia with
lidocaine compared to prilocaine.
AB - The purpose of this double-blind study was to investigate the incidence of
transient neurological symptoms after the use of isobaric lidocaine and isobaric
prilocaine for spinal anaesthesia. Seventy patients (ASA 1-2, age between 18 and
70 years) were randomly assigned to two groups of 35 patients each, to receive
either isobaric 2% lidocaine 4 ml or isobaric 2% prilocaine 4 ml intrathecally,
at the L3-4 interspace. One patient in the prilocaine group could not be included
because data were incomplete. On the first postoperative day, patients were
evaluated for transient neurological symptoms. Pain was scored on a 10-point
scale. Seven patients (20%) in the lidocaine group had transient neurological
symptoms with a mean pain score of 5.3, whereas no patient in the prilocaine
group had these complaints (p = 0.006). Symptoms disappeared within 4 days.
Prilocaine results in a lower incidence of transient neurological symptoms than
lidocaine intrathecally and therefore it is more suitable for short surgical
procedures.
PMID- 11012501
TI - Paediatric intensive care transfers: 2.
PMID- 11012502
TI - Paediatric intensive care transfers 3.
PMID- 11012503
TI - A further comment
PMID- 11012504
TI - Stress and trainees.
PMID- 11012505
TI - Testing breathing systems.
PMID- 11012506
TI - Fibreoptic intubation through a laryngeal mask airway facilitated by a guide
wire.
PMID- 11012507
TI - Auditing the application of cricoid pressure.
PMID- 11012508
TI - Classification of laryngoscopic view.
PMID- 11012509
TI - A novel method of delivering vasoconstrictors to the nasal passage.
PMID- 11012510
TI - Failure of a 'Diprivan 1%' prefilled propofol syringe.
PMID- 11012512
TI - Tec 6 vaporiser raises the temperature.
PMID- 11012513
TI - The effect of smoking on postoperative nausea and vomiting.
PMID- 11012515
TI - Cardiac arrest after video-assisted thoracoscopic drainage of pleural effusion.
PMID- 11012516
TI - An unexpected difficult extubation.
PMID- 11012517
TI - Urgent abdominal aortic aneurysm repair and sickle cell trait.
PMID- 11012518
TI - Survival following ruptured aortic aneurysm.
PMID- 11012519
TI - Internal jugular cannulation using a long spinal needle as a seeker needle.
PMID- 11012520
TI - Bronchoscopic confirmation of the correct placement of the tracheostomy tube
during translaryngeal tracheostomy.
PMID- 11012522
TI - Transurethral vaporisation of the prostate.
PMID- 11012523
TI - Iatrogenic foreign body in the bronchus.
PMID- 11012524
TI - Succinylcholine-associated postoperative myalgias...not always!
PMID- 11012525
TI - Anaesthesia and angiotensin II receptor antagonist.
PMID- 11012526
TI - Remifentanil and seizures.
PMID- 11012527
TI - Anaphylaxis caused by neostigmine.
PMID- 11012528
TI - Soya bean oil in Diprivan.
PMID- 11012529
TI - Vancomycin causes dangerous precipitation when infused with gelatin fluid.
PMID- 11012530
TI - Should Mendelson's syndrome be renamed?
PMID- 11012531
TI - Identification of the epidural space.
PMID- 11012532
TI - Keep epidurals simple.
PMID- 11012533
TI - Pitfalls of moisturising creams.
PMID- 11012534
TI - Generic propofol: what's the point?
PMID- 11012536
TI - Protecting pacemakers in prone patients.
PMID- 11012535
TI - Airway protection during percutaneous tracheostomy.
PMID- 11012537
TI - Hemolipodialysis attenuates oxidative stress and removes hydrophobic toxins.
AB - Uremic patients undergoing hemodialysis often have increased oxidant stress and
accumulation of uremic toxins. Hemodialysis, per se, often can exacerbate oxidant
stress and may be inefficient at removing hydrophobic or protein bound toxins. We
describe a new hemodialytic method that incorporates liposomes and antioxidants
to remove hydrophobic/uremic toxins and minimize free radical mediated damage. In
vitro experiments measured advanced oxidation protein products (AOPP),
malonaldehyde, reactive carbonyls, and the removal of platelet activating factor
(PAF) and bilirubin during extracorporeal circulation with or without liposomes.
We observed a significant reduction of oxidation products as well as a
significant removal of PAF and bilirubin compared to normal hemodialysis.
PMID- 11012538
TI - Carotid intima-media thickness and plaques in hemodialysis patients.
AB - Atherosclerosis is accelerated in hemodialysis patients. Using B-mode
ultrasonography, we compared intima-media thickness (IMT) and the prevalence of
plaques in the common carotid and internal carotid arteries in 28 randomly
selected hemodialysis patients with that in 28 age- and sex-matched normal
controls. The IMT values of the common carotid and internal carotid arteries were
higher in hemodialysis patients than in controls with more hemodialysis patients
having plaques. In hemodialysis patients, there was a relationship between age
and IMT in the common carotid arteries, in the area of bifurcation, and in the
internal carotid arteries. We found no relationship between IMT and
atherosclerotic risk factors or duration of hemodialysis treatment. IMT at all
sites correlated with the number of plaques. Age was the only significant
determinant for number of plaques. The results indicate that hemodialysis
patients showed advanced atherosclerosis in the carotid arteries compared with
age- and sex-matched normal subjects.
PMID- 11012540
TI - Plasmapheresis-related hypotension.
AB - Hypotension is an uncommon complication of procedures involving extracorporeal
circulation, including plasmapheresis. From November 1993 to March 1999, we
treated 139 patients who underwent a total of 1,137 sessions of double filtration
plasmapheresis (DFP). Hypotension was defined as a systolic blood pressure (BP) <
80 mm Hg or any decrease of systolic BP with systemic reactions. A total of 17
(1.5%) episodes of hypotension were documented in 15 patients during the study
period. Hypotensive episodes occurred in 2.3% of patients with inflammatory
neuropathy, 1.2% of patients with myasthenia gravis, and 1.2% of patients with
all other medical diseases. Involvement of the autonomic nerve system (ANS) and a
low baseline BP were associated with the occurrence of hypotension. Eight (47%)
of 17 episodes were symptomatic and 2 were complicated with seizure. Patients
with symptomatic hypotension had a higher level of systolic BP prior to DFP and a
larger drop of systolic BP and pulse rate during hypotensive attacks compared to
asymptomatic patients. Most hypotensive episodes were resolved briefly after
intravenous infusion of saline within 30 min. Eight (47%) of the hypotensive
episodes occurred during the first session of DFP treatment. Twelve (71%) of 17
episodes occurred during the last half period of treatment; 6 of them were noted
during the terminating stage of DFP. In conclusion, in this series plasmapheresis
related hypotension occurred in 1.5% of DFP sessions and had a higher prevalence
in patients with ANS instability and low BP. Extra caution in monitoring BP
during DFP therapy is warranted in these vulnerable patients, especially during
the termination phase of the first DFP session.
PMID- 11012539
TI - Ex vivo biocompatibility of avidin-agarose: a new device for direct adsorption of
biotinylated antibodies from human whole blood.
AB - Radioimmunotherapy using radiolabeled antitumor antibodies (RAA) is limited by
the toxicity of unbound antibodies in the circulation. Removal of excessive
antibodies by affinity-adsorption could therefore allow the administration of
increased dosages of RAA while decreasing their adverse effects. Recently, avidin
agarose (AA) minicolumns were used in animal experiments for the removal of
biotinylated antibodies from whole blood exploiting the high affinity binding of
biotin to avidin (pK 1015 M-1). This study was performed to evaluate the ex vivo
biocompatibility of AA minicolumns with human blood. Ten ml AA minicolumns were
perfused online ex vivo in the single pass mode with fresh blood from 8 healthy
donors at a flow rate of 6.25 ml/min. The anticoagulation consisted of 0.5 IU
heparin plus 0.0-2.1 mg citrate per ml of blood. In Part 1 of the study (40 min
perfusion, n = 4), the optimal anticoagulation was found to be 0.5 IU heparin
plus about 1 mg citrate per ml of blood. In Part 2 of the study, four 80 min test
runs were performed. No signs of hemolysis were found, and the thrombogenicity of
the AA gel was negligible. Cell counts and column inlet pressures remained
constant; toward the end of the 80 min test-runs, some activation of blood cells
(elastase, beta-thromboglobulin), the complement system (C3a, C5a) and the
plasmatic coagulation (thrombin-antithrombin complex) was detectable. A moderate
initial bradykinin release rapidly subsided to very low levels. In summary, AA
minicolumns showed good biocompatibility upon contact with human whole blood and
merit further investigation in a closed-loop system for a potential application
of direct tumor antibody removal by hemoperfusion.
PMID- 11012541
TI - Artificial sensorimotor integration in spinal cord injured subjects through
neuromuscular and electrotactile stimulation.
AB - Spinal cord injured (SCI) subjects lack sensorimotor functions. Neuromuscular
electrical stimulation (NMES) systems have been used to artificially restore
motor functions, but without proprioceptive feedback, SCI subjects can control
NMES systems only when they can see their limbs. In a gait restoration system,
the subject looks down to the ground to be aware of where his foot is while in a
grasping activity, maximum grip strength is employed regardless of the force that
is required to perform tasks. This report focuses on artificial sensorimotor
integration. Multichannel stimulation was used to restore motor functions while
encoded tactile sensation (moving fused phantom images) relating to artificially
generated movements was provided by electrotactile stimulation during walking and
grasping activities. The results showed that the sensorimotor integration
attained yielded both the recognition of artificial grasp force patterns and a
technique to be used by paraplegics allowing spatial awareness of their limb
while walking.
PMID- 11012542
TI - Age dependency of neointima formation on vascular prostheses in dogs.
AB - Neointima formed quickly on vascular prostheses implanted in young dogs but not
in aged dogs. Previously, we found that impeding neointima formation on vascular
prostheses occurred more frequently in aged animals. From these observations, we
hypothesized that neointima formation was age-dependent in dogs. To test the
hypothesis, 26 fabric Dacron vascular prostheses were analyzed. Half of them were
retrieved from aged dogs (more than 13 years old) while the other half were from
young ones (less than 1 year old). The grafts were harvested at 8 weeks and 3
months after implantation. The graft surfaces were photographed and analyzed by
computer for the ratio of the areas with and without thrombus. Light and scanning
electron microscopic observation revealed that most of the thrombus-free areas
were lined with endothelial cells. Then the endothelialized areas were
calculated. Using data obtained from macroscopic, light microscopic, and scanning
electron microscopic observations, the arithmetic means were calculated as the
degree of neointima formation. In young animals, the degrees at 8 weeks and at 3
months were 89.1 +/- 8.5% (mean +/- SD) and 95.7 +/- 3.3%, respectively. In old
animals, they were 27.9 +/- 5.9% and 31.5 +/- 6. 8%, respectively. From these
results, we concluded that neointima formation was age-dependent in dogs.
PMID- 11012543
TI - Is avoidance of air contact necessary for the in vitro evaluation of
thrombogenicity in mechanical circulatory assist devices?
AB - An effective in vitro protocol for the investigation of thrombogenicity can
provide many advantages in the development of mechanical circulatory assist
devices. Strict avoidance of air contact with blood recently was proposed for
reliable in vitro evaluation. This study was performed to confirm the necessity
of avoidance of air contact for the in vitro test of thrombogenicity in a rotary
pump. Two sets of mock circuits with the same rotary blood pumps, reservoirs, and
connecting tubes were made. In one system, blood came in contact with air while
the other did not. The test blood was heparinized at the dose of 1 IU per 1 ml of
blood. The tests were terminated at an activated coagulation time of 1.5 times
the control value. The levels of hematocrit, platelet, factors VIII and XII,
fibrinogen, thromboxane B2, and plasma-free hemoglobin were measured during the
procedures. After the experiments, the thrombi formed were observed, measured,
and compared with those formed in in vivo circumstances. The tests were repeated
12 times. There were no statistically significant differences between the 2
groups in hematologic parameters and the amounts of thrombi formed. The thrombi
observed in both groups showed the same pathologic findings as those formed in
vivo with the exception of intermittent multiple air bubbles found in thrombi of
the air-contact group. In conclusion, the effect of air contact in the in vitro
investigation of thrombogenicity was negligible while the proposed in vitro test
models of thrombogenesis in the mechanical circulatory assist device proved to be
reliable.
PMID- 11012544
TI - Analytical investigation of leakage flow in disk clearance of a magnetically
suspended centrifugal impeller.
AB - Leakage flow through the disk clearance of a magnetically suspended centrifugal
blood pump is essential for a good washout. An analytical approach, based on the
theory of lubrication, is used to predict the leakage volume flow rate,
nondimensional radial velocity, nondimensional mean pressure distribution, and
comparative shear stress distribution for different disk clearance geometry under
varying rotational speeds. The results showed that nondimensional mean pressure
distribution and nondimensional radial velocity distribution along the clearance
are independent of rotational speed. The flow through the gap depends on a
nondimensional parameter S that denotes the ratio of centrifugal forces to the
head generating capability of the impeller. It was found that an impeller having
a lower S has less possibility of flow reversals in the gap, and gap with maximum
height at the outside radius also is more susceptible to flow reversals at the
impeller surface. The comparative shear stress within the gap reveals that, in
general, the scalar stress is below 500 N/m2.
PMID- 11012545
TI - Is erythrocyte damage prevented by gardos effect in hemodialyzed uremic patients?
AB - The purpose of this study was to determine the changes of calcium and potassium
content in red blood cells (RBC) from uremic patients during a hemodialysis (HD)
session. In 17 uremic patients on HD, the calcium and potassium content of RBC
was determined in 3 blood samples collected at 0 min-HD (pre-HD), 45 min-HD, and
240 min-HD (end-HD) during a 4 h HD session. The calcium and potassium content of
RBC also was determined in 20 normal subjects (controls). The mean values (+/-SD)
of RBC calcium content in patients at 0 min-HD, 45 min-HD, and 240 min-HD were
1.95 +/- 0.34, 2.82 +/- 0.50, and 2. 05 +/- 0.4 microg/ml, respectively, and in
controls 0.61 +/- 0.14 microg/ml. These values show that the RBC calcium in
patients was generally significantly higher (p < 0.0001) in comparison to that of
controls. The RBC calcium at 45 min-HD was significantly higher as compared to
that at 0 min-HD and at 240 min-HD (p < 0.0001). The mean values (+/-SD) of RBCs'
potassium in uremic patients at the previously mentioned measurements were 95.9
+/- 3.34, 92.5 +/- 4.32, and 93.85 +/- 3.89 mEq/L, respectively, and in controls
98.46 +/- 2. 30 mEq/L. These values show that RBC potassium of patients was
generally significantly lower in comparison to controls (0 min-HD: p < 0.01, 45
min-HD and 240 min-HD: p < 0.001). Potassium decrease also was significantly
lower at 240 min-HD (p < 0.01) and even lower at 45 min-HD (p < 0.001) compared
to that at 0 min-HD. In conclusion, uremic patients during an HD session present
a high calcium and a low potassium content of erythrocytes. These changes may
prevent swelling of the cells (Gardos effect).
PMID- 11012546
TI - Serial measurement of polyethylene wear of well-fixed cementless metal-backed
acetabular component in total hip arthroplasty: an over 10 year follow-up study.
AB - Serial radiographic measurements of polyethylene wear were performed in 38 hips
(33 patients) with primary cementless total hip arthroplasty (THA). The average
follow-up period was 131.8 months. All prostheses were assessed as
radiographically stable at the latest follow-up. A two-dimensional method was
used to calculate the relative migration of the femoral head center to the cup
center. The average total linear wear and wear rate were 1.22 mm and 0.11
mm/year, respectively. The degree of wear in the first 2 postoperative years
accounted for nearly 40% of the total wear at the end of the study (average
follow up: 131.8 +/- 10.0 months, +/-SD). The migration of the femoral head at an
average period of 3. 4 months after operation accounted for 56% of the amount of
wear in the first 2 years. Wear rate decreased gradually with time and stabilized
after the fourth year. However, in 2 patients, a progressive increase in the wear
rate was associated with severe osteolysis and failure of THA. Both creep and
wear contributed to the femoral penetration into the polyethylene liner. The
influence of creep cannot be ruled out, especially in the early period after
operation. Polyethylene wear is a multifactorial process, and the study of
individual wear patterns might be useful in identifying patients who are at risk
of late failure of THA.
PMID- 11012547
TI - Radiopacity and fatigue characterization of a novel acrylic bone cement with
sodium fluoride.
AB - Acrylic bone cement must provide good radiographic visibility and good long-term
mechanical resistance in joint replacements. A new formulation of cement with 6%
barium sulfate and 6% sodium fluoride was developed (Fluoride Bone Cement).
Barium sulfate is a necessary addition to allow radiographic visibility although
it reduces the mechanical strength of the material. Sodium fluoride promotes bone
formation. However, its effect on the mechanical behavior is currently unknown
while its influence on radiopacity can only be roughly estimated. The aim of this
investigation was to establish if the new formulation would be suitable for
clinical trials. In this respect, a mechanical (fatigue test) and radiographic
(optical density measurements on x-ray films) characterization was performed on a
typical commercially available cement with barium sulfate added and on the
Fluoride Bone Cement. It was demonstrated that the fluoride cement has a
(marginally) superior fatigue strength and comparable radiopacity to commercial
radiopaque cements.
PMID- 11012548
TI - Transaortic inflow and outflow cannula for centrifugal mechanical assistance.
AB - A specific cannula allowing single site transaortic inflow and outflow
cannulation for centrifugal assist devices is described. The cannula is inserted
through a straight 18 mm collagen coated Dacron tube anastomosed to the anterior
aspect of the ascending aorta. The inflow conduit of the cannula is positioned
into the left ventricle through the aortic valve, and the end hole of the outflow
conduit is positioned in the ascending aorta. The cannula was evaluated in vivo
in 3 adult pigs by the institution of a centrifugal pump for left ventricular
support. Optimal flow varied between 5 and 6 L/min and mean aortic pressure
between 55 and 70 mm Hg throughout the 3 days of left ventricular support.
Recently, we employed this cannula in a patient who was not able to be weaned
from cardiopulmonary bypass for the institution of left ventricular support using
a centrifugal pump. The cannula provided effective inflow and outflow drainage
with an optimal flow of 5.2 L/min throughout the 72 h of support. The patient was
successfully weaned from support on the fourth postoperative day. This rational
transaortic approach of cannulation using this specific cannula is a refined
implantation technique which allows direct left ventricular inflow drainage,
reduces the time of implantation, spares left ventricular myocardium, avoids
bleeding that is sometimes encountered at other cannulation sites, and avoids
compression of the heart by cannulas.
PMID- 11012549
TI - Implantation of one piece biventricular assist device by left thoracotomy in an
ovine model.
AB - In this report, we describe an operative procedure for our implantable 1 piece
biventricular assist device (BiVAD) based on a moving actuator mechanism, using
an ovine model. Our implantable BiVAD is a volumetric coupled 1 piece unit
including right and left blood sacs and an actuator assembly based on the moving
actuator mechanism. The BiVAD was controlled by fixed rate control with 75 bpm
for the most part. Both the left and the right full ejection modes with the
maximum stroke angle were selected to minimize blood stasis in the blood sacs
because of low assist flow condition. Three Corriedale sheep were used for the
device implantation by a left thoracotomy incision. Cannulation was successfully
performed in all cases. Although exposability of the right atrial appendage
varied from animal to animal, the insertion of the cannula was easily performed.
The cannulas were connected to the pump-actuator assembly in the preperitoneal
pocket. All 3 animals survived the experimental procedure. During implantation of
the device, in the 1 month survival animal, pump flow was maintained between 2.0
L/min and 2.5 L/min, mean aortic pressure was 90-110 mm Hg, and mean pulmonary
artery pressure was 20-30 mm Hg. The left and right atrial pressure were
maintained between 0 and 5 mm Hg. In conclusion, this ovine model for
implantation of the 1 piece BiVAD can be an effective alternative for testing in
vivo biocompatibility of the device although it needs more consideration for
anatomical fittability for future human application.
PMID- 11012551
TI - Drug-induced proarrhythmic effects: assessment of changes in QT interval.
PMID- 11012550
TI - Macrolide - induced clinically relevant drug interactions with cytochrome P-450A
(CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin.
PMID- 11012553
TI - In vitro evaluation of potential in vivo probes for human flavin-containing
monooxygenase (FMO): metabolism of benzydamine and caffeine by FMO and P450
isoforms.
AB - AIMS To determine the FMO and P450 isoform selectivity for metabolism of
benzydamine and caffeine, two potential in vivo probes for human FMO. METHODS
Metabolic incubations were conducted at physiological pH using substrate
concentrations of 0.01-10 mM with either recombinant human FMOs, P450s or human
liver microsomes serving as the enzyme source. Products of caffeine and
benzydamine metabolism were analysed by reversed-phase h.p.l.c. with u.v. and
fluorescence detection. RESULTS CYP1A2, but none of the human FMOs, catalysed
metabolism of caffeine. In contrast, benzydamine was a substrate for human FMO1,
FMO3, FMO4 and FMO5. Apparent Km values for benzydamine N-oxygenation were 60 +/-
8 microM, 80 +/- 8 microM, > 3 mM and > 2 mM, for FMO1, FMO3, FMO4 and FMO5,
respectively. The corresponding Vmax values were 46 +/- 2 min-1, 36 +/- 2 min-1,
< 75 min-1 and < 1 min-1. Small quantities of benzydamine N-oxide were also
formed by CYPs 1A1, 1A2, 2C19, 2D6 and 3A4. CONCLUSIONS: FMO1 and FMO3 catalyse
benzydamine N-oxygenation with the highest efficiency. However, it is likely that
the metabolic capacity of hepatic FMO3 is a much greater contributor to plasma
levels of the N-oxide metabolite in vivo than is extrahepatic FMO1. Therefore,
benzydamine, but not caffeine, is a potential in vivo probe for human FMO3.
PMID- 11012552
TI - Parkinson's disease and CYP1A2 activity.
AB - AIMS MPTP, a neurotoxin which induces parkinsonism is partially metabolized by
the enzyme CYP1A2. Smoking appears to protect against Parkinson's disease (PD)
and cigarette smoke induces CYP1A2 activity. Thus, we investigated the hypothesis
that idiopathic PD is associated with lower CYP1A2 activity using caffeine as a
probe compound. METHODS CYP1A2 activity was assessed using saliva paraxanthine
(PX) to caffeine (CA) ratios. Caffeine half-life was also estimated from salivary
concentrations of caffeine at 2 and 5 h post dose. 117 treated and 40 untreated
patients with PD and 105 healthy control subjects were studied. RESULTS PX/CA
ratios were 0. 57, 0.93 and 0.77 in treated patients, untreated patients and
healthy control subjects, respectively, with no significant differences between
study groups (95% CI: treated patients vs controls -0.24, 0.57; untreated
patients vs controls -0.75, 0.35). However, patients with PD (treated or
untreated) had caffeine half-lives shorter than that in controls (treated
patients: 262 min, untreated patients: 244 min, controls: 345 min; 95% CI:
controls vs treated patients 23, 143 (P = 0.003); controls vs untreated patients
19, 184 (P = 0.011)). Amongst the patients with PD, caffeine half-life was also
inversely related to the age of onset of disease (P = 0.012); gender and
concomitant drugs did not influence this significantly. CONCLUSIONS: Based on
PX/CA ratio, there was no evidence of decreased CYP1A2 activity in patients
compared with control subjects. The observed decrease in the elimination half
life of caffeine in PD may be caused by increased CYP2E1 activity, an enzyme that
also contributes to the metabolism of caffeine. The latter warrants further
investigation.
PMID- 11012554
TI - Population pharmacokinetics of doxorubicin, etoposide and ifosfamide in small
cell lung cancer patients: results of a multicentre study.
AB - AIMS: To determine the population pharmacokinetic (PK) parameters of doxorubicin
(Dox), etoposide (Eto) and ifosfamide (Ifo) in small cell lung cancer (SCLC)
patients, to assess the potential relationship between those parameters and to
estimate the impact of individual morphological and biological covariates on
patients' PK parameters. METHODS: Twenty-four patients with either SCLC limited
to the thorax or extensive SCLC entered the study. All but one received at least
two 3 day courses of the standard AVI (Dox 50 mg m-2 day 1, Eto 120 mg m-2 day
1,2,3, Ifo 2000 mg m-2 day 1,2) regimen. Individual blood samples were collected
during each course and data on 47 courses were available. Data were analysed with
the NONMEM program. Dox, Eto and Ifo plasma concentrations were studied with
multicompartment (3, 2 and 2, respectively) models. Inter-individual and
interoccasion (course-to-course) variabilities were estimated. The influence of
individual covariates (age, sex, stage of the disease, weight, height, body
surface area, serum creatinine, total protein, LDH, ASAT, ALAT, alkaline
phosphatase, gamma-GT, bilirubin) on PK parameters was also assessed.
Correlations between individual PK parameters of Dox, Eto and Ifo were explored
by using Pearson's correlation coefficient. RESULTS: Multiple data were available
for each patient. Dox clearance (CL) and volume of distribution (Vd) were 32.0 l
h-1 and 9.3 l (Inter-individual variability: 17.2% and 19.2%). Eto CL (l h-1) and
Vd were, respectively, 3.34-0.0083* serum creatinine (micromol l-1) and 6.38 l
(interindividual variability: 15.6% and 18.7%). Ifo CL and Vd at day 1 were 5.6 l
h-1 and 26.0 l (interindividual variability: 10.1% and 17.2%, respectively).
Estimation of course-to-course variability improved the precision of PK models in
some cases. No correlation was observed between the respective PK parameters of
each drug. Of individual covariates tested, only serum creatinine correlated with
Eto CL (r = -0.37, P < 0.001). Self-induction of the metabolism of Ifo was
apparent (mean CL increase from day 1 to day 2 : 42%) and individually correlated
with the CL value at day 1 (r = -0.61, P < 0.001). CONCLUSIONS: Assessment of
potential relationships between individual systemic exposure of chemotherapy and
therapeutic endpoints (tumour response, toxicity and survival) will be required
to adjust drugs dosages based on individual PK parameters rather than
questionable body-surface area. However, all three drugs in the AVI regimen
should be monitored simultaneously.
PMID- 11012555
TI - Effect of altered gastric emptying and gastrointestinal motility on metformin
absorption.
AB - AIMS: The purpose of this in vivo human study was to assess the effect of altered
gastric emptying and gastrointestinal motility on the absorption of metformin in
healthy subjects. METHODS: An open-label, three treatment, three period crossover
study was conducted in 11 healthy volunteers. Each subject received 550 mg
metformin hydrochloride in solution alone; 5 min after a 10 mg i.v. dose of
metoclopramide; and 30 min after a 30 mg oral dose of propantheline. Metformin
solution was radiolabeled by the addition of 99mTc-DTPA. The gastrointestinal
transit of the solution was monitored by gamma scintigraphy and the
pharmacokinetic data were correlated with the scintigraphic findings. RESULTS:
Scintigraphic data indicated that pretreatment with metoclopramide decreased
gastric emptying time and increased gastrointestinal motility while pretreatment
with propantheline had the opposite effect. The systemic disposition of metformin
was not altered by pretreatment with metoclopramide and propantheline, as judged
by unchanged renal clearance and elimination half-life of metformin. Extent of
metformin absorption was essentially unchanged after pretreatment with
metoclopramide. However, AUC(0,infinity) and % UR (percent dose excreted
unchanged in urine) generally increased with increase in gastric emptying time
and small intestinal transit times. GI overlay plots showed that the absorption
phase of metformin plasma profile always coincided with gastric emptying and the
beginning of decline of metformin plasma concentrations was usually associated
with the colon arrival. Only in cases where the intestinal transit was
drastically prolonged by propantheline pretreatment, was a decline in plasma
levels observed prior to colon arrival. CONCLUSIONS: Metformin is primarily
absorbed from the small intestine. The extent of metformin absorption is improved
when the gastrointestinal motility is slowed. These findings have significant
implications in the design of a metformin modified release dosage form.
PMID- 11012556
TI - Effect of an oral contraceptive preparation containing ethinylestradiol and
gestodene on CYP3A4 activity as measured by midazolam 1'-hydroxylation.
AB - AIMS: To characterize the effect of an oral contraceptive (OC) containing
ethinylestradiol and gestodene on the activity of CYP3A4 in vivo as measured by
the 1'-hydroxylation of midazolam. METHODS: In this randomised, double-blind,
cross-over trial nine healthy female subjects received either a combined OC (30
microg ethinylestradiol and 75 microg gestodene) or placebo once daily for 10
days. On day 10, a single 7.5 mg dose of midazolam was given orally. Plasma
concentrations of midazolam and 1'-hydroxymidazolam were determined up to 24 h
and the effects of midazolam were measured with three psychomotor tests up to 8
h. RESULTS: The combined OC increased the mean AUC of midazolam by 21% (95% CI 2%
to 40%; P = 0.03) and decreased that of 1'-hydroxymidazolam by 25% (95% CI 10% to
41%; P = 0.01), compared with placebo. The metabolic ratio (AUC of 1'
hydroxymidazolam/AUC of midazolam) was 36% smaller (95% CI 19% to 53%; P = 0.01)
in the OC phase than in the placebo phase. There were no significant differences
in the Cmax, tmax, t(1/2) or effects of midazolam between the phases.
CONCLUSIONS: A combined OC preparation caused a modest reduction in the activity
of CYP3A4, as measured by the 1'-hydroxylation of midazolam, and slightly
increased the AUC of oral midazolam. This study suggests that, at the doses used,
ethinylestradiol and gestodene have a relatively small effect on CYP3A4 activity
in vivo.
PMID- 11012557
TI - A double-blind, placebo-controlled study to assess tolerability, pharmacokinetics
and preliminary pharmacodynamics of single escalating doses of Z13752A, a novel
dual inhibitor of the metalloproteases ACE and NEP, in healthy volunteers.
AB - AIMS: The objective of this study was to evaluate the tolerability of a novel
dual ACE-NEP inhibitor, Z13752A, after the oral administration of rising single
doses in healthy volunteers. This study was also a preliminarily investigation of
Z13752A pharmacodynamics (PD) and pharmacokinetics (PK). METHODS: In this
randomized, placebo-controlled, sequential study, two alternating panels of eight
healthy male volunteers each (six subjects receiving the active treatment + two
subjects receiving placebo) were treated with increasing oral doses of Z13752A:
10, 50, 200, and 600 mg were given to panel I and 20, 100, 400 and 800 mg were
given to panel II. The study was double-blind relative to placebo or active
treatment, and was open with respect to the dose levels. The same volunteer
received placebo only once. RESULTS: Single oral doses of Z13752A, as high as 800
mg, were well tolerated. Only six mild-to-moderate adverse events mainly
headache, were reported and appeared to be of little clinical relevance. After
administration of 200, 400, 600 and 800 mg of Z13752A, a nonsignificant fall in
diastolic blood pressure was detected, in both the standing and supine position.
After single oral doses of Z13752A, ACE inhibition appeared to be significant at
all the doses tested, linearly correlated with the dose and was almost complete
at doses > or = 100-200 mg. NEP inhibition was indicated by elevation of ANP and
cGMP plasma concentrations in almost all subjects. In the 200-800 mg dose range,
Z13752A produced a 50-100% increase of plasma cGMP levels and a 50-80% elevation
in urinary cGMP concentrations. Detectable plasma levels of Z13752A were found in
all the treated subjects. Z13752A was well and rapidly absorbed, with peak
concentrations reached approximately 2.5 h after administration. The mean
apparent elimination half-life from plasma was approximately 12 h. The
pharmacokinetics of Z13752A after single oral doses were characterized by low
intersubject variability and appeared to be dose-independent. CONCLUSIONS:
Z13752A showed a good single dose tolerability profile at doses up to 800 mg. The
pharmacokinetic data indicate that Z13752A administered orally is rapidly
absorbed and available to the systemic circulation in humans. The relatively slow
clearance indicates that a once-a-day dose regimen could be considered for
Z13752A.
PMID- 11012558
TI - Pharmacodynamic and pharmacokinetic profile of S 17092, a new orally active
prolyl endopeptidase inhibitor, in elderly healthy volunteers. A phase I study.
AB - AIMS: The aim of this study was to characterize the pharmacodynamics and the
pharmacokinetics of S 17092, a new orally active prolyl endopeptidase inhibitor
following single and repeated administration in elderly healthy volunteers.
METHODS: This was a double-blind, randomized, placebo-controlled, single and
multiple dose study in elderly healthy male and female volunteers (n = 36). Four
doses were investigated in sequential order: 100, 400, 800 and 1200 mg. Each dose
was administered orally once a day in single administration and then, after a 1
week washout period, during 7 days. Pharmacodynamics were assessed by measurement
of plasmatic prolyl endopeptidase (PEP) activity, quantitative
electroencephalogram (EEG) and psychometric tests. S 17092 concentrations in
plasma were quantified by high performance liquid chromatography with tandem mass
spectrometric detection. RESULTS: PEP activity in plasma was dose-dependently
inhibited both after administration of a single dose and after repeated doses of
S 17092. The mean maximal inhibition was obtained within 0.5-2 h after dosing,
while inhibition lasted at least 12 h after dose administration. S 17092 appeared
to be a centrally active substance as it induced statistically significant
modifications in EEG compared with placebo. S 17092 at 100 mg exerted an acute
increase in alpha band following single administration at 4 h and 8 h postdosing.
When administered repeatedly over 7 days S 17092 did not appear to induce
significant lasting central nervous system (CNS) effects. In psychometric tests,
response times in the numeric working memory were significantly reduced compared
with placebo, following the 800 mg dose. There were some beneficial residual
effects of the 1200 mg dose on day 13: delayed word recall and word recognition
sensitivity improved compared with the declines noted under placebo. Maximum
measured concentration (Cmax) and area under the curve (AUC) parameters increased
in proportion to the dose. The terminal half-life (t(1/2)) values ranged between
9 and 31 h on day 1 and between 7 and 18 h on day 14. A high interindividual
variability was observed at all dose levels. S 17092 was well tolerated with no
clinically significant changes in laboratory or physical parameters observed at
any dose. CONCLUSIONS: S 17092 had a potent, dose-dependent inhibitory effect on
plasmatic PEP, increased alpha band EEG at the 100 mg dose and improved
performance in two verbal memory tests at the 1200 mg dose while there were
disruption to the vigilance task. The results obtained in elderly healthy
subjects indicated that S 17092 is suitable for once-daily dosing without any
serious adverse events.
PMID- 11012559
TI - Effects of high ambient temperature on parasympathetically mediated
cardiovascular reflexes in normal man.
AB - AIMS: To examine the effects of high ambient temperature ('heat stressor') on
parasympathetically mediated cardiovascular reflexes (power of respiratory sinus
dysrhythmia; change in heart rate elicited by change in posture from lying to
standing ['30 : 15 ratio']). METHODS: Twelve healthy male volunteers participated
in four weekly sessions, each of which was associated with one treatment
condition (placebo at an ambient temperature of 22 degrees C; propranolol 40 mg
at 22 degrees C; placebo at 40 degrees C; propranolol 40 mg at 40 degrees C),
according to a balanced double-blind design. Heart rate was recorded by ECG,
finger tremor (7-12 Hz) with an accelerometer strapped to the middle finger of
the nondominant hand, and sublingual temperature by a mercury thermometer. Power
of finger tremor and the variations of the R-R intervals of the ECG were obtained
from Fourier transformations of the data. Data were analysed by analysis of
variance, with repeated measures using a significance criterion of P < 0.05;
individual comparisons of active treatment with placebo and of data obtained at
40 degrees C with those obtained at 22 degrees C were made with Fisher's Least
Significant Difference test. RESULTS: Heart rate was increased by the heat
stressor, and this increase was abolished by propranolol. The heat stressor
reduced the power of respiratory sinus dysrhythmia and the 30 : 15 ratio, and
increased the power of physiological finger tremor. Propranolol did not affect
heat stressor-induced changes in the parasympathetic cardiac reflexes, but
reduced the heat stressor-induced enhancement of finger tremor. CONCLUSIONS: The
increase in the power of physiological finger tremor at high ambient temperature
is consistent with sympathetic activation, whereas the reduction in the power of
respiratory sinus dysrhythmia and 30 : 15 ratio indicates a decrease in
parasympathetic activity. These results demonstrate that high ambient temperature
may induce vagal withdrawal in the heart.
PMID- 11012560
TI - The rates of common adverse events reported during treatment with proton pump
inhibitors used in general practice in England: cohort studies.
AB - AIMS: To estimate the rates of common adverse events in patients treated with the
proton pump inhibitors omeprazole, lansoprazole and pantoprazole in general
practice in England. METHODS: In prescription-event monitoring cohort studies,
data on dispensed prescriptions prescribed by general practitioners in England
soon after each drug was launched were linked to subsequent clinical events
recorded by the prescriber. 16 205 patients prescribed omeprazole between June
1989 and June 1990, 17 329 patients prescribed lansoprazole between May and
November 1994, and 11 541 patients prescribed pantoprazole between December 1996
and June 1997 were studied. RESULTS: The commonest adverse events in the
omeprazole, lansoprazole and pantoprazole cohorts were diarrhoea (incidence: 0.
18, 0.39 and 0.23 per 1000 days of exposure, respectively); nausea/vomiting
(incidence: 0.16, 0.22 and 0.18 per 1000 days of exposure, respectively);
abdominal pain (incidence: 0.17, 0.21 and 0. 17 per 1000 days of exposure,
respectively); and headache (incidence rates: 0.10, 0.17 and 0.15 per 1000 days
of exposure, respectively). The remaining adverse events occurred at rates of
less than 0.11 per 1000 days of exposure. There were little absolute differences
in the rates of most events between the three proton pump inhibitors. However,
diarrhoea was more commonly associated with lansoprazole compared with omeprazole
(rate difference: 0.21 per 1000 days of exposure; 95% CI 0.17, 0.25; rate ratio:
2.11; 1.78, 2.51), and there was a clear age-response relationship. CONCLUSIONS:
Adverse events occurred relatively infrequently in all three cohorts. There were
only small absolute differences in event rates between the three drugs, although
these data suggest the hypothesis that lansoprazole is associated with more
frequent occurrence of diarrhoea, particularly in the elderly.
PMID- 11012561
TI - The pharmacokinetics of trinitroglycerin and its metabolites in patients with
chronic stable angina.
AB - AIMS: To study the pharmacokinetics of trinitroglycerin (GTN) and its four
metabolites in angina patients during their transient use of transdermal GTN tape
following intravenous administration of GTN. METHODS: Four patients received a
GTN tape following intravenous administration of 0.1 microg kg-1 min-1 GTN, and
the other four patients received two GTN tapes following intravenous
administration of 0.2 microg kg-1 min-1 GTN. RESULTS: Plasma concentrations of
GTN in both groups during tape application showed a slight decrease for the hour
after the application of the tape and then were con- stant for 24 h. In contrast,
the concentrations of dinitroglycerins (GDNs) and mononitroglycerins (GMNs)
depended on the duration of previous intravenous administration of GTN. Neither
significant cardiovascular changes nor undesirable complications were observed
during the study. CONCLUSIONS: The results suggest that appropriate replacement
of intravenous GTN administration with transdermal tape application could
maintain a therapeutic GTN level.
PMID- 11012562
TI - Nebivolol decreases systemic oxidative stress in healthy volunteers.
AB - AIMS: Nebivolol is a selective, vasodilatory beta1-adrenergic receptor antagonist
which has been suggested to possess additional antioxidative properties. The aim
of the present study was to assess the actions of nebivolol in antihypertensive
doses on systemic oxidative stress in healthy volunteers, reflected by 24 h
urinary excretion of 8-iso-PGF2alpha. METHODS: In a double-blind, cross-over
study, 12 healthy volunteers received 5 mg nebivolol once daily or placebo for a
total of 7 days, separated by a wash out period of 2 weeks. After each treatment
period 24 h urinary excretion of 8-iso-PGF2alpha was determined by gas
chromatography-tandem mass spectrometry. RESULTS: After the 7 day treatment
period nebivolol decreased significantly urinary excretion of 8-iso-PGF2alpha by
24% from 55.3 +/- 5.1 pmol mmol-1 creatinine during the placebo period to 42.3 +/
4.7 pmol mmol-1 creatinine (mean +/- s.e. mean, P = 0. 01), a mean decrease of
13 pmol mmol-1 creatinine (95% CI: -22.8; -3. 1). CONCLUSIONS: Our data show for
the first time that nebivolol decreases systemic oxidative stress in young
healthy volunteers.
PMID- 11012563
TI - Influences on plasma cortisol of different formulations of beclomethasone
dipropionate.
PMID- 11012564
TI - Recent advances in the molecular genetics of congenital and acquired primary
adrenocortical failure.
PMID- 11012565
TI - Characterization of a novel DNA polymorphism in the human CYP21 gene and
application for DNA diagnosis of congenital adrenal hyperplasia.
AB - OBJECTIVES: Congenital adrenal hyperplasia (CAH) is a common endocrine disorder
and CYP21 (21-OH, EC 1.14.99.10) deficiency is the most common cause of the
disease. The presence of a pseudogene and a wide range of mutation types often
makes DNA diagnosis difficult. Analysis of mutant alleles from patients with CAH
identified a new DNA polymorphism in exon 10. To test the usefulness of this
polymorphism, linkage analysis was performed using three RFLP's at both end of
the CYP21 gene in patients and controls. DESIGN AND PATIENTS: Genomic DNA was
extracted from 21 unrelated patients and 39 unaffected individuals. Haplotyping
analysis was performed for three RFLPs, MspI and Fnu4HI in intron 2 and a new
SmaI RFLP in exon 10. All three polymorphic sites were characterized by DNA
sequencing and usefulness of these RFLPs for DNA diagnosis was tested in
patients' families. MEASUREMENT: CAH patients were diagnosed by clinical symptoms
and biochemical tests. Allele frequencies and heterozygosities were studied for
three RFLP's in patients and controls using polymerase chain reaction (PCR).
RESULTS: A new SmaI RFLP showed a sequence difference as G or A at the nucleotide
position 2694 in exon 10. Sequences at the MspI and Fnu4HI polymorphic sites were
T or C at the nucleotide position 395 and 453, respectively. All of these RFLPs
showed biallelic DNA polymorphisms and codominant segregation in family analysis.
Heterozygosities were 0.31 for MspI, 0.48 for Fnu4HI and 0.44 for SmaI in normal
individuals. There was no linkage disequilibrium for three RFLPs between patients
and controls. CONCLUSIONS: The SmaI RFLP can be useful for linkage analysis and
DNA diagnosis in conjunction with RFLPs in intron 2 in CAH families because the
polymorphic site is within the active gene at the 3' end. DNA sequencing results
revealed that these RFLPs were created by gene conversions as with other
mutations in the CYP21 gene.
PMID- 11012566
TI - Tall stature in familial glucocorticoid deficiency.
AB - OBJECTIVE: Familial glucocorticoid deficiency (FGD) has frequently been
associated with tall stature in affected individuals. The clinical, biochemical
and genetic features of five such patients were studied with the aim of
clarifying the underlying mechanisms of excessive growth in these patients.
PATIENTS AND METHODS: Five patients with a clinical diagnosis of FGD are
described in whom the disorder resulted from a variety of novel or previously
described missense or nonsense mutations of the ACTH receptor (MC2-R). All
patients demonstrated excessive linear growth over that predicted from parental
indices and increased head circumference. RESULTS: Growth hormone and IGF-I
values were normal. Growth charts suggest that the excessive growth is reduced to
normal following the introduction of glucocorticoid replacement. A characteristic
facial appearance including hypertelorism, marked epicanthic folds and prominent
frontal bossing was noted. CONCLUSIONS: These findings indicate that ACTH
resistance resulting from a defective ACTH receptor may be associated with
abnormalities of cartilage and/or bone growth independently of the GH-IGF-I axis,
but probably dependent on ACTH actions through other melanocortin receptors.
PMID- 11012567
TI - Comparison of one week 0900 h serum cortisol, low and standard dose synacthen
tests with a 4 to 6 week insulin hypoglycaemia test after pituitary surgery in
assessing HPA axis.
AB - OBJECTIVE: To compare the use of 0900 h serum cortisol and both low and standard
dose Synacthen tests, one week after pituitary surgery with an insulin
hypoglycaemia test performed 4-6 weeks after surgery in assessing the integrity
of the hypothalamic-pituitary-adrenal (HPA) axis. DESIGN: 0900 h basal serum
cortisol was measured on days 6 and 7 after pituitary surgery (24 h off
replacement hydrocortisone) followed by a low dose Synacthen test (1 microg
intravenously) on day 6 and a standard dose Synacthen test (250 microg
intramuscularly) on day 7. Three to 5 weeks later an insulin hypoglycaemia test
was performed on all patients. Both low and standard dose Synacthen tests were
performed on control subjects using an identical protocol. SUBJECTS: Forty-two
patients (21 male, 21 female), median age 49 years (range 23-73) who had
pituitary surgery (Cushing's disease excluded). One patient had undergone repeat
surgery for residual tumour and was studied following each operation. Sixteen
healthy normal volunteers, median age 37 years (range 21-55). MEASUREMENTS: Serum
cortisol measured by radioimmunoassay. RESULTS: Two standard deviations below the
mean serum cortisol (logarithmic transformation) in the normal volunteers 30
minutes after low dose Synacthen (1 microg) was 496 nmol/l and after standard
dose Synacthen (250 microg) was 504 nmol/l. A normal response was therefore taken
as serum cortisol > 500 nmol/l at 30 minutes in both tests (using 496 and 504
nmol/l did not alter results). 0900 h serum cortisols 1 week after surgery were >
250 nmol/l in 31 patients and 29 of these had a normal response to hypoglycaemia
(peak serum cortisol > 550 nmol/l). Of the remaining two patients, one had 0900 h
serum cortisol on day 6 and 7 after surgery of 405 and 441 nmol/l with a peak
serum cortisol response to hypoglycaemia of 451 nmol/l; the other patient had
0900 h serum cortisols of 416 and 251 nmol/l and a peak cortisol response to
hypoglycaemia of 498 nmol/l. All eight patients who had a 0900 h serum cortisol <
100 nmol/l failed a subsequent insulin hypoglycaemia test. Seven discrepancies
were noted between the low dose Synacthen test and the insulin hypoglycaemia test
in the 41 patients who had both tests. In six of these, a subnormal response to
low dose Synacthen was followed by a normal response to hypoglycaemia. Three
discrepancies were noted between the standard dose Synacthen test and the insulin
hypoglycaemia test in the 40 patients who had both tests. In all three cases a
normal response to Synacthen was followed by a subnormal response to
hypoglycaemia. CONCLUSIONS: A 0900 h serum cortisol < 100 nmol/l (24 h off
replacement hydrocortisone) indicated ACTH deficiency and need for lifelong
steroid replacement. A 0900 h serum cortisol > 450 nmol/l one week after
pituitary surgery is highly suggestive of a normal cortisol response to
hypoglycaemia. A 0900 h serum cortisol between 250 and 450 nmol/l one week after
pituitary surgery permits safe withdrawal of steroid therapy pending an insulin
hypoglycaemia test 1 month after surgery. Patients with 0900 h serum cortisol
between 100 and 250 nmol/l should continue replacement steroids until definitive
testing. Low dose and standard dose Synacthen tests 1 week after pituitary
surgery are unreliable and should not be used.
PMID- 11012568
TI - Adrenal responsiveness to high, low and very low ACTH 1-24 doses in obesity.
AB - OBJECTIVE: To investigate adrenal activity in visceral obesity in which adrenal
hyperactivity has been hypothesized. This could reflect hypothalamus-pituitary
alterations leading to slight hyperfunction of the adrenal. Primary adrenal
hypersensitivity to ACTH drive in obesity has also been suggested. However, it
has also been reported that dehydroepiondrosterone (DHEA) levels in obesity are
reduced and it has been hypothesized that this could play a role in the increased
cardiovascular risk in obese patients. SUBJECTS: We have studied seven obese
women with visceral adiposity (OB, age: 33.6+/-3.3 years, BMI: 33.8+/-1.3 kg/m2,
WHR: 0.88+/-0.01). The results in OB were compared with those recorded in a group
of age-matched normal women (NS, age: 30+/-1.3 years, BMI: 19.9+/-0.4 kg/m2, WHR:
0.76+/-0.02). METHODS: We have studied the cortisol (F), aldosterone (A) and DHEA
responses to ACTH 1-24 administered at low (LD, 0.5 microg/m2) or very low (VLD,
0.125 microg/m2) dose followed by a second challenge with supramaximal dose (HD,
250 microg). RESULTS: Basal F, A and DHEA levels in OB were similar to those in
NS. The peak F responses to ACTH were dose-related in both groups. At each dose
the F peaks in OB (VLD: 495.6+/-43.9 nmol/l, HD: 722.3+/-67.7 nmol/l; LD: 519.2+/
46.0 nmol/l, HD: 729.6+/-44.7 nmol/l) were similar to those in NS (VLD: 556.7+/
45.9 nmol/l, HD: 704.8+/-20.7 nmol/l; LD: 511.8+/-22.8 nmol/l, HD: 726.7+/-26.5
nmol/l). The peak A responses to ACTH were dose-related in both groups. At each
dose, the A peaks in OB (VLD: 0.55+/-0.03 pmol/l, HD: 0.79+/-0.09 pmol/l; LD:
0.63+/-0.04 pmol/l, HD: 0.78+/-0.09 pmol/l) were similar to those in NS (VLD:
0.8+/-0.10 pmol/l, HD: 0.86+/-0.09 pmol/l; LD: 0.8+/-0.10 pmol/l, HD: 0.95+/-0.12
pmol/l). The peak DHEA responses to ACTH were dose-related in both groups. At
each dose the DHEA peaks in OB (VLD: 58.6+/-13.3 nmol/l, HD: 61.9+/-13.1 nmol/l;
LD: 55.18+/-6.4 nmol/l, HD: 72.3+/-9.8 nmol/l) were similar to those in NS (VLD:
54.3+/-8.2 nmol/l, HD: 57.8+/-8.2 nmol/l; LD: 42.2+/-3.7 nmol/l, HD: 56.9+/-4.3
nmol/l). CONCLUSIONS: This study shows that the cortisol, aldosterone and
dehydroepiondrosterone responses to high, low and very low ACTH doses in obese
women overlap with those in age-matched lean controls; these findings suggest
normal sensitivity of the different zones of the adrenal cortex to ACTH in
obesity.
PMID- 11012569
TI - Vascular reactivity in acromegalic patients: preliminary evidence for regional
endothelial dysfunction and increased sympathetic vasoconstriction.
AB - BACKGROUND AND OBJECTIVES: Hypertension is found in one-third of acromegalic
patients. An heterogenous distribution of cardiac output has been recently
demonstrated in acromegalic patients with an increased blood flow at the level of
the upper limb, suggesting that acromegalic patients may have some degree of
endothelial dysfunction. Elsewhere, studies involving hypopituitary GH-deficient
adults have shown that GH and/or IGF-I may have direct effect on endothelial
function. SUBJECTS AND METHODS: We thus compared cutaneous vasoreactivity
responses in 10 normotensive patients with active acromegaly (A) (six women and
four men) aged 25-59 (mean, 43.2 years), whose basal GH and IGF-I levels ranged
from 7.4 to 158 mU/l and from 401 to 1690 microg/l, respectively, and in 10
normal age- and sex-matched controls (NC) by means of Laser Doppler flowmetry at
the levels of the palm and the dorsum of the right hand. Circulatory skin
velocities were studied basally and after increasing skin temperature to 44
degrees C (in order to study direct nonspecific vasodilatation response which is
independent of endothelial or autonomous nervous system and reflects normal
vascular muscle function), after shear-stress (known to produce flow-dependent
vasodilatation, mediated by nitric oxyde (NO) originating from endothelial cells)
and after cold-stress applied on the opposite hand (known to produce vaso
constriction mediated by the sympathetic nervous system). RESULTS: The warm test
induced a significant (P<0.001) and similar increase in both dorsal and palmar
skin perfusion in A (mean +/- SD) (240+/-96 and 238+/-134%, respectively) and NC
(232+/-137 and 233+/-73, respectively). Ischaemia release induced a significant
increase in both dorsal and palmar skin blood flows in the two groups (P<0.001),
but reactivities in acromegalic patients were about one half of those measured in
controls (22.9+/-16.2% (A) vs. 46.9 25% (NC), 2P<0.02, at the level of the
dorsum; and 45.0+/-43.6% (A) vs. 104.7+/-40.1 (NC), 2P<0.01, at the level of the
palm). Cold pressor test resulted in significant decreases in both cutaneous
flows (P<0.01) in the two groups, with a larger vasoconstriction (that did not
reach statistical significance) in acromegalic patients as compared with controls
(P< 0.10). CONCLUSION: Vascular smooth cell ability to produce skin
vasodilatation is normal but endothelium-dependent vasodilatation appears to be
impaired while sympathetic-mediated vasoconstrictive response might be increased
in acromegaly. This endothelial dysfunction may contribute to hypertension and
represent a risk factor for cardiovascular complications in acromegaly.
PMID- 11012570
TI - Sustained reduction in circulating cholesterol in adult hypopituitary patients
given low dose titrated growth hormone replacement therapy: a two year study.
AB - OBJECTIVE: To study the effects of short (6 months) and longer-term (up to 24
months) growth hormone (GH) replacement therapy using a dose titration regimen,
on lipid and glucose metabolism in GH-deficient, hypopituitary adults. DESIGN: On
going open study of GH treatment up to 24 months. Measurements were performed at
baseline and at 6, 12, 18 months and 2 years during therapy (data shown at 6
months and 2 years only). Using a dose titration regimen the median GH dose used
to achieve and maintain IGF-I levels above the median, but below the upper limit
of the age-related reference range (median IGF-I 202.5 microg/l, range 76-397
microg/l), was 1.2 IU daily (range 0.4-3 IU) [0.8 IU/day, males; 1.6 IU/day,
females]. PATIENTS: Ninety GH-deficient hypopituitary adults (54 female, median
age 48 years, range 19-79 years) entered the study and 24 (14 female, median age
45 years, range 32-79 years) have concluded the 2 year period of assessment.
MEASUREMENTS: Body mass index (BMI), waist and hip circumference ratio (WHR),
fasting lipids, glucose and glycated haemoglobin (HbA1c) levels were measured at
6 month intervals during GH therapy. RESULTS: Using the dose titration regimen,
compared to pretreatment values, total and low density lipoprotein (LDL)
cholesterol levels were significantly lower at 6 months (mean +/- SEM, 5.61+/-0.1
vs. 5.25+/-0.1, and 3.85+/-0.19 vs. 3.43+/-0.26, respectively, P<0.05), and were
maintained throughout the study. Male patients had significantly lower
pretreatment total and LDL cholesterol levels than females (mean +/- SEM, 5.33+/
0.16 mmol/l vs. 5.7+/-0.12 mmol/l and 3.8+/-0.23 mmol/l vs. 3.92+/-0.29 mmol/l,
respectively, P< 0.05). A decrease in total cholesterol was confined to patients
with pretreatment total cholesterol levels above 5.8 mmol/l; patients with the
highest pretreatment cholesterol levels (> 6.4 mmol/l) obtained the greatest
cholesterol reduction (mean +/- SEM, 7.13 +/- 0.14 mmol/l vs. 5.76+/-0.31 mmol/l,
P<0.05). A cholesterol-lowering effect of GH therapy was evident in patients who
had elevated pre-GH total cholesterol levels even if they were already receiving
and continuing lipid lowering medication (mean +/- SEM, 5.62+/-0.22 vs. 5.03+/
0.285, P<0.05). A modest increment in high density lipoprotein (HDL)-cholesterol
was evident at 18 months but there was no significant change in triglycerides at
any time point. Fasting plasma glucose increased significantly at 6 months but
remained within the reference range. Glycated haemoglobin increased significantly
at 6 months and was maintained throughout the study; one patient developed frank
diabetes mellitus while receiving treatment. There was a weak but significant
correlation between the increment in glycated haemoglobin and pretreatment BMI (r
= + 0.215, P<0.05). CONCLUSION: The effect of GH on lowering total and low
density lipoprotein-cholesterol is more prominent in patients with higher
pretreatment cholesterol levels and is evident even in patients receiving other
lipid-lowering medication. A modest increment in mean fasting glucose (within the
reference range) and mean glycated haemoglobin persisted throughout the study.
One patient developed diabetes mellitus. A GH replacement regimen using low dose
and careful titration to avoid elevated IGF-I levels and adverse effects is
associated with sustained beneficial effects on circulating lipids.
PMID- 11012572
TI - Expression of thyroid receptor isoforms in the human fetal central nervous system
and the effects of intrauterine growth restriction.
AB - BACKGROUND: Congenital hypothyroidism is known to be associated with mental
retardation which, if recognized promptly, is largely prevented by thyroid
hormone replacement. Intrauterine growth restriction (IUGR) is a major cause of
perinatal mortality and morbidity, and is also associated with neurodevelopmental
delay. Fetuses with IUGR have reduced circulating concentrations of free
thyroxine (T4) and free triiodothyronine (T3), leading to the hypothesis that a
reduction in the tissue effects of thyroid hormones in the central nervous system
(CNS) may contribute to neurodevelopmental morbidity. Since thyroid hormone
effects are mediated through binding to specific nuclear thyroid hormone
receptors (TRs), we have defined the pattern of TR isoform expression in the CNS
throughout normal human development and have compared TR expression in the CNS of
normal fetuses with those affected by IUGR. METHODS: Samples of normal human
fetal brain from first and second trimesters were obtained at surgical
termination of pregnancy. Appropriately grown and third trimester fetuses
affected by Intrauterine growth restriction (IUGR) were also investigated after
unexplained stillbirth at post mortem examination. Reverse transcriptase
polymerase chain reaction (RT-PCR) was used to examine the expression of TR
isoform mRNAs in frozen cerebral cortex from 10 to 16 weeks gestation. TR protein
expression in human fetal brains (both cerebral hemispheres and cerebellum) was
also examined in formalin fixed sections and expression of TR alpha1, alpha2,
beta1 and beta2 isoforms being defined using semiquantitative
immunocytochemistry. RESULTS: RT-PCR revealed the presence of mRNAs encoding TR
alpha1, beta1 and beta2 isoforms and the nonfunctional TRalpha2 variant in the
fetal cerebral cortex from week 10 of human pregnancy. Immunostaining of the
fetal brain revealed TR alpha1 and alpha2 protein from week 11 of human
gestation. Expression of all TR isoform proteins was largely confined to the
pyramidal neurones of the cerebral cortex and the Purkinje cells of the
cerebellum with increasing receptor expression evident with gestational age.
Semiquantitative observer scoring showed that by the second trimester, there was
a marked increase in the proportion of pyramidal and Purkinje cells expressing TR
isoforms, while by the third trimester, all these cells immunostained. Comparison
of TR immunostaining in the cerebral cortex and cerebellum from IUGR fetuses (n =
18) matched for gestational age to normal fetuses revealed a lower intensity of
expression of all the TR isoforms confirmed by observer scoring and
quantification using TR protein immunofluoresence (P<0.01). CONCLUSIONS: Our
findings indicate both pre- and post-translational expression of TR alpha and
beta isoforms in the cerebral cortex of first trimester fetuses. These findings
support the view that the transplacental passage of thyroid hormone in early
gestation may be critical to neurological development. Our finding that in severe
IUGR the expression of TR isoforms in the human fetal cerebral cortex and
cerebellum was significantly reduced, in association with reduced circulating
thyroid hormone concentrations indicate that changes in free ligand and receptors
may affect CNS development. These findings should prompt further investigation of
the potential therapeutic role of peripartum thyroid hormone treatment.
PMID- 11012571
TI - Functional characterization of five constitutively activating thyrotrophin
receptor mutations.
AB - OBJECTIVE: Gain of function mutations of the thyrotrophin receptor (TSHR) affect
several functional characteristics, such as cAMP and inositol phosphate (IP)
accumulation, cell surface expression and TSH affinity. In this study we compared
five constitutively activating TSHR mutations, four receptors with a point
mutation (S505N, L629F, I630L, V656F) and a nine amino acid (aa) deletion mutant
(aa positions 613-621) for these functional parameters in parallel transfection
experiments. METHODS: The wild-type TSHR (wt) and TSHRs containing the mutations
S505N, L629F, I630L, V656F and the deletion 613-621 (all cloned in the expression
vector pSVL) were transiently expressed in COS-7 cells in parallel experiments.
Forty-eight hours after transfection the basal and stimulated cAMP and inositol
phosphate accumulation as well as the cell surface expression (by FACS and
ELISA), KD-values and TSHR down regulation by different stimuli were determined.
RESULTS: In contrast to the very different values for specific constitutive
activity (sca) (ranging from 7.5 to 100.3-fold wt) and very different levels of
receptor cell surface expression (11-94% wt level) the basal cAMP accumulation
determined in transfected COS-7 cells was surprisingly uniform (6.5-8.0 over wt
basal). None of the point mutated receptors constitutively activates the
phospholipase C cascade. In contrast the deletion 613-621 mutant showed
constitutive activity for the IP pathway with a twofold increase in basal IP
accumulation compared to the wild type TSHR. All investigated TSHR-mutants showed
a TSH-stimulated receptor down-regulation, which seems to be independent of the
phospholipase C pathway. CONCLUSIONS: The uniform basal cAMP values in spite of
the large variation in specific constitutive activity values suggest that the COS
7 cell overexpression system used for the in vitro characterization is partly
regulated. This regulation is most likely due to receptor down regulation. The
TSHR deletion mutant (613-621) showed a constitutive activity for both the
Galphas and the Galphaq/11 pathways. The TSH-mediated IP-stimulation by this
mutant contrasts with its unresponsiveness to TSH for cAMP accumulation and
therefore supports the model of different active conformations of the TSHR.
PMID- 11012573
TI - Goitre prevalence and thyroid abnormalities at ultrasonography: a comparative
epidemiological study in two regions with slightly different iodine status.
AB - OBJECTIVE: The association between severe iodine deficiency and endemic goitre is
well established, but little information is available on the relation between
milder degrees of iodine deficiency and goitre prevalence. SUBJECTS: In a
comparative epidemiological study performed in two regions in Denmark, we
examined 4649 subjects from the general population, women aged 18-65 years and
men aged 60-65 years. METHODS: Ultrasonography and palpation of the thyroid was
performed in all participants. Iodine excretion was measured in casual urine
samples. Previous thyroid disease was detected by questionnaires, personal
interviews and tracing of records. RESULTS: The median iodine excretion was 61
microg/l (mild iodine deficiency (ID)) and 45 microg/l (moderate ID) in the two
regions. Median thyroid volume at ultrasonography was 11. 9 ml (mild ID) and 13.6
ml (moderate ID), P <0.001, and thyroid enlargement was found in 15.0% (mild ID)
and 22.6% (moderate ID), P<0.001. Goitre prevalence increased in both regions
with age to the age group 40-45 years, but not after that age. Subjects who had
moved from the moderate ID to the mild ID area had the same prevalence of thyroid
enlargement as the subjects staying permanently in the mild ID area. Thyroid
nodules at ultrasonography were found in 30% in both regions, but nodules were
larger and more often palpable in the moderate ID area. Palpable goitre was found
in 9.8% (mild ID) and 14.6% (moderate ID), P<0.001. The greatest regional
difference in thyroid abnormalities was found among men. CONCLUSION: Marked
differences in the prevalence of thyroid abnormalities were found in these
regions with modest differences in iodine excretion.
PMID- 11012574
TI - Postpartum thyroid dysfunction in women with normal thyroid function during
pregnancy.
AB - OBJECTIVE: The aim of this study was to establish the risk of postpartum thyroid
dysfunction (PPTD) in women who had normal thyroid function during pregnancy and
no history of thyroid disease. DESIGN: Four thousand and twenty-two consecutive
pregnant women were screened for thyroid function and antithyroid antibody. Among
women with normal thyroid function during pregnancy and no history of thyroid
disease, thyroid function were assessed in 131 of 388 antithyroid antibody
positive (Group I) and 1030 of 3503 antibody negative (Group II) women at 1 and 3
months postpartum. In Group I women who experienced PPTD, the frequency of later
manifestation of Hashimoto's disease was compared according to titres of
antithyroid antibodies. MEASUREMENTS: Blood samples in early pregnancy, and at 1
month and 3 months postpartum were obtained using the dried blood spot method.
Levels of fT4 were measured by RIA, TSH by fluoroimmunoassay or ELISA,
antimicrosome antibody (AMC) and antithyroglobulin antibody (ATG) by indirect
agglutination reactions. RESULTS: The prevalence of PPTD at 1 month and 3 months
postpartum were found to be 6.9% and 21.3% in Group I, and 5.3% and 4.7% in Group
II, respectively. The prevalence of PPTD was significantly higher at 3 months
postpartum in Group I (P<0.05). 27.3% of women with PPTD in Group I were later
found to have Hashimoto's disease and 9.1% manifested hypothyroidism without
goitre. A high AMC titre (> or = 25600) at 3 months postpartum in women with PPTD
was related to the manifestation of Hashimoto's disease. AMC titres of PPTD women
and women who developed Hashimoto's disease were significantly higher than those
of control women who did not experience PPTD. CONCLUSION: A high prevalence of
PPTD was found in women with antithyroid antibodies who were euthyroid during
pregnancy. Prolonged follow-up of the subsequent thyroid function may be needed
in women who experience PPTD and/or show a high titre of antithyroid antibody.
PMID- 11012575
TI - How common are polycystic ovaries and the polycystic ovarian syndrome in women
with Cushing's syndrome?
AB - OBJECTIVE: Women with Cushing's syndrome (CS) may present with menstrual
irregularity and symptoms/signs of hyperandrogenism, a phenotype similar to that
of the polycystic ovarian syndrome (PCOS); however, currently there are no data
on the prevalence of either polycystic ovaries (PCO) and/or PCOS in patients with
CS. The aim of this study was to investigate their presence among women of
reproductive age presenting with CS by analysing clinical, endocrinological and
ultrasonographic features. DESIGN: Prospective study of all women within the
reproductive age (range 18-40 years) who presented with CS between August 1994
and January 2000. SUBJECTS AND METHODS: Thirteen women (median age 32 years,
range 18-39 years) with CS were evaluated. The diagnosis of CS was based on the
presence of appropriate clinical features and an elevated serum midnight cortisol
with failure to suppress 0900 hours serum cortisol to less than 50 nmol/l
following a formal low-dose dexamethasone suppression test (LDDST). All women had
their clinical features relevant to possible hyperandrogenism, menstrual disorder
and infertility recorded, and circulating gonadotrophins, oestradiol, androgens
and SHBG levels measured; ovarian ultrasonography was performed during their
initial assessment. Relevant MR/CT imaging of the pituitary and/or adrenal glands
was performed. RESULTS: Eleven women had ACTH-dependent CS [nine Cushing's
disease (CD), one ectopic ACTH syndrome due to a bronchial carcinoid, one
periodic CS of unknown origin); two patients had ACTH-independent CS (adrenal
adenomas). All women with CS had at least one symptom/sign of hyperandrogenism
(13 hirsutism, seven acne, five male-pattern alopecia). Nine women (70%) had
menstrual disturbances (four oligomenorrhoea, four amenorrhoea, one
polymenorrhoea) while four women (30%) had a normal menstrual pattern. Serum
oestradiol levels for the group as a whole were similar to those observed in the
early follicular phase of normally menstruating women; however, seven women had
low oestradiol, LH and FSH levels suggestive of hypogonadotrophic hypogonadism.
Serum androgen levels (testosterone, androstendione and DHEAS), even in the
presence of symptoms/signs of hyperandrogenism, were within the normal reference
range but SHBG levels were uniformly decreased even in women with normal
menstrual cycles. There was a negative correlation between urinary free cortisol,
but not mean serum cortisol, and serum oestradiol, testosterone and SHBG levels
(r = - 0.8, r = - 0.86 and r = - 0.66, P<0.02, P<0.01 and P<0.05, respectively),
but not LH or FSH levels. Despite the fact that seven of these 13 patients lacked
normal gonadotrophin stimulation, ovarian volumes of both ovaries were relatively
preserved: right 7.3 ml, range 2.8-12.8 ml, and left 5.3 ml, range 2.3-13 ml.
Women who were defined as oestrogen sufficient (E2 > 140 pmol/l) had higher serum
androstenedione, and lower urinary free cortisol levels, than women who were
oestrogen deficient (E2 < 140 pmol/l). Six of the 13 women (46%) had ovarian
morphology suggestive of PCO, four of six oestrogen sufficient women and two of
seven oestrogen deficient women. The results did not differ according to the
underlying cause of CS. CONCLUSIONS: PCO and PCOS are common in women with
Cushing's syndrome; women with Cushing's syndrome and only moderately elevated
cortisol secretion maintain gonadotrophin stimulation to the ovary with normal
oestradiol levels, in contrast to women with Cushing's syndrome and higher
cortisol secretion who develop hypogonadotrophic hypogonadism. However, even in
the latter group, high ovarian volumes were maintained and some had ovarian
morphology suggestive of PCO.
PMID- 11012576
TI - The prevalence of polycystic ovaries in women with a history of gestational
diabetes.
AB - OBJECTIVE: Women with a history of gestational diabetes mellitus (GDM) and women
with polycystic ovary syndrome (PCOS) both demonstrate abnormalities in insulin
action and secretion, and both are at increased risk of developing type 2
diabetes. To determine whether these similarities reflect a common
pathophysiological basis, we examined the prevalence of ultrasound-based
polycystic ovarian morphology in a large multiethnic group of women with a
history of GDM and a group of women who had normal glucose tolerance during
pregnancy. PATIENTS AND DESIGN: We studied 91 women with previous GDM (48
European, 20 South Asian, 10 Afro-Caribbean and 13 of other or mixed ethnicity)
and 73 normoglycaemic control women (56 European, one South Asian, 14 Afro
Caribbean and two of other or mixed ethnicity), a median (interquartile range) of
20 (11-36) and 29 (17-49) months postpartum, respectively. A detailed history was
taken, and the prevalence of PCO morphology on ultrasound scan was assessed.
Fasting lipids, insulin, glucose status, gonadotrophins and testosterone were
measured. Estimates of beta-cell function (%B) and insulin sensitivity (%S) were
derived using the HOMA algorithm. RESULTS: Women with previous GDM had higher
fasting glucose (5.4 (4. 8-6.0) vs. 4.7 (4.4-5.0) mmol/l, P<0.0001) and features
reminiscent of syndrome X: higher BMI (26.4 (22.8-31.4) vs. 23.8 (21. 0-27.5)
kg/m2, P = 0.002), waist/hip ratio (0.82 (0.79-0.88) vs. 0. 77 (0.73-0.81),
P<0.0001), fasting insulin (165 (68-299) vs. 54 (24-156) pmol/l, P<0.0001),
triglycerides (1.1 (0.8-1.6) vs. 0.8 (0.6-1.1) mmol/l, P<0.0001) and lower
insulin sensitivity (%S) (27 (16-62) vs. 86 (34-139)%, P<0.0001) compared to
control women. The prevalence of PCO was higher in the previous GDM group than in
the control subjects (47/91 (52%) vs. 20/73 (27%), chi2 = 9.86, P = 0. 002
overall, odds ratio 2.7, P = 0.007 by logistic regression allowing for
ethnicity). There was no difference in any metabolic parameter between the post
GDM PCO group and the post-GDM normal ovaries group, but irregular cycles were
more prevalent in the PCO group (22/47 (47%) vs. 9/44 (21%), chi2 = 7.03, P =
0.008). CONCLUSIONS: We found a higher prevalence of polycystic ovarian
morphology in women with a history of gestational diabetes. Among the women with
previous gestational diabetes, irregular cycles were more prevalent in the PCO
group than in the women with normal ovarian morphology, but no other differences
in endocrine or metabolic parameters were detected. These findings confirm an
association between PCO and gestational diabetes and suggest that women with
gestational diabetes display metabolic abnormalities irrespective of ovarian
morphology.
PMID- 11012577
TI - Growth and endocrine disorders in multisystem Langerhans' cell histiocytosis.
AB - INTRODUCTION: Langerhans' cell histiocytosis is a rare disorder, with diabetes
insipidus occurring in up to half of patients. Causes of growth failure include
the illness itself, treatments used and growth hormone insufficiency. PATIENTS
AND METHODS: We identified all patients with an endocrinopathy secondary to
Langerhans' cell histiocytosis (LCH). Growth data were analysed from all patients
with multisystem involvement. RESULTS: Of 144 patients with multisystem LCH, 50
had an endocrinopathy, 49 of whom had diabetes insipidus. Growth hormone
insufficiency (GHI) was present in 21 patients, seven of whom had other anterior
pituitary deficiencies as well (gonadotrophin deficiency + GHI n = 2,
gonadotrophin deficiency + TSH deficiency + GHI n = 2, panhypopituitarism n = 3).
GH insufficiency, the development of which appeared to be independent of
pituitary radiation, occurred at a median age of 8.3 years (4.7-18 years) and at
a median interval of 3.5 years (0-11.8 years) after diagnosis of LCH. The median
height SDS at diagnosis of growth hormone insufficiency was -2.9. Thirteen of the
patients with growth hormone insufficiency attained final height with a median
height SDS of -1.2. The final height SDS of 15 patients without GH insufficiency
was closer to target height SDS, but not statistically different from that of the
GH insufficient group. CONCLUSIONS: GH therapy significantly improves growth in
GH insufficient patients with Langerhans' cell histiocytosis. Early institution
of GH therapy may further improve height outcome. However, most children with
Langerhans' cell histiocytosis regardless of endocrine function, failed to reach
target height.
PMID- 11012578
TI - Androgens and penile erection: evidence for a direct relationship between free
testosterone and cavernous vasodilation in men with erectile dysfunction.
AB - OBJECTIVE: Androgens are essential in the maintenance of nitric oxide-mediated
erectile activity in the rat. The objective of the present study was to
investigate the role of androgens in regulating trabecular smooth muscle
relaxation in the corpus cavernosum in response to vasoactive challenge in men
with erectile dysfunction (ED). DESIGN: Retrospective, double-blind correlation
analyses. PATIENTS: Fifty-two impotent patients without confounding risk factors
for ED were obtained from a total of 250 undergoing diagnostic evaluation.
MEASUREMENTS: All patients had dynamic colour duplex ultrasound (D-CDU) and
hormonal evaluation for LH, total and free testosterone, SHBG and oestradiol.
RESULTS: Based upon D-CDU results patients were diagnosed as having arteriogenic
(AR, n = 18; mean age 51) or corporeal venocclusive (CVO, n = 13; mean age 49)
ED; in other patients (n = 21, mean age 43) a diagnosis of psychogenic (P)-ED was
made by comprehensive psychogenic testing and confirmed by normal D-CDU results.
AR and CVO patients had altered compliance of cavernous arteries recorded by D
CDU [20-25% lower resistive index (RI) than patients with psychogenic ED], and
lower free testosterone (FT) levels than psychogenic patients [42.3 +/-3.5 SE and
49.3+/-5.2 vs. 75.2+/-7.6 pmol/l, respectively; P<0.01]. More important, in all
patients there was a strong direct correlation between resistive index values and
FT levels (r = 0.47, P = 0.002); the relationship was maintained also when
adjusted for age, SHBG and oestradiol (r = 0.37, P = 0.02). CONCLUSIONS: These
results indicate that in men with erectile dysfunction low free testosterone may
correlate independently of age with the impaired relaxation of cavernous
endothelial and corporeal smooth muscle cells to a vasoactive challenge. These
findings give clinical support to the experimental knowledge of the importance of
androgens in regulating smooth muscle function in the penis.
PMID- 11012579
TI - Adrenal hyperandrogenism in adolescent girls with a history of low birthweight
and precocious pubarche.
AB - OBJECTIVE: Girls with precocious pubarche (PP) are at increased risk for ovarian
dysfunction, hyperinsulinism and dyslipidaemia in adolescence, in particular when
PP is preceded by reduced fetal growth. However, it is not known whether PP girls
still have adrenal hyperandrogenism after puberty and if so, which fraction of PP
girls develops so-called functional adrenal hyperandrogenism (FAH), an entity
characterized by ACTH-dependent 17-ketosteroid excess. PATIENTS AND DESIGN: Data
were longitudinally collected from 47 girls with PP: at birth (weight for
gestational age), at diagnosis of PP (age 6.7+/- 1.1 years) and in adolescence
(age 15.0+/-1.9 years). MEASUREMENTS: Serum dehydroepiandrosterone sulphate
(DHEAS) and androstenedione were measured at PP diagnosis, as well as the 17
hydroxyprogesterone (17-OHP) response to ACTH; postpubertal evaluation included
assessment of adrenal and ovarian function, and of insulin responses to a glucose
load. PP girls were considered to have FAH in adolescence if both DHEA and
androstenedione responses to ACTH were excessive (> 1500 ng/dl and > 350 ng/dl,
respectively). RESULTS: At diagnosis of PP, girls had high DHEAS and
androstenedione levels, as well as high 17-OHP responses to ACTH. In adolescence,
PP girls had a normal BMI, presented with mild hirsutism and had high baseline
and post-ACTH concentrations of most adrenal androgens, low SHBG levels and
tended to have hyperinsulinemia and to present biological signs of ovarian
hyperandrogenism. More than a third of the PP cohort developed FAH in
adolescence. Neither baseline DHEAS, androstenedione, nor post-ACTH 17-OHP values
at diagnosis of PP predicted the development of FAH in adolescence. In PP girls,
only a low weight at birth was found to be significantly associated with
subsequent FAH. CONCLUSIONS: These longitudinal findings in girls with PP point
to the possibility of an endocrine sequence of prenatal onset: low weight at
birth, PP in childhood and adrenal hyperandrogenism in adolescence. The
pathophysiological mechanisms underpinning this newly recognized sequence remain
to be identified.
PMID- 11012580
TI - Optic chiasmal herniation--an under recognized complication of dopamine agonist
therapy for macroprolactinoma.
AB - The initial presentation of macroprolactinoma with visual field impairment,
especially in males, is well recognized. Successful treatment with dopamine
agonist therapy is characterized by a reduction in hyperprolactinaemia and often
rapid and progressive resolution of the visual impairment. A small proportion of
patients may subsequently develop a secondary deterioration in both their visual
fields and visual acuities despite normalization of prolactin levels and tumour
shrinkage. When pituitary apoplexy can be excluded this may result from traction
on the optic chiasm which is pulled down into the now partially empty sella. We
report a series of seven patients in whom chiasmal traction is believed to be the
cause of their secondary deterioration in visual acuity occurring after dopamine
agonist therapy for macroprolactinoma. The clinical history of two patients both
of whom had rapid resolution of field defect with bromocriptine therapy but
subsequently developed a recurrence of their bitemporal hemianopia is detailed.
In both patients MRI scanning showed not only tumour involution but also marked
optic chiasm herniation into the pituitary fossa. Surgical treatment was
considered too risky; but on reduction of bromocriptine dosage the field defect
improved in both cases; there was a modest elevation of prolactin and a degree of
tumour re-expansion. The latter is believed to have released tethering of the
optic chiasm and/or its vascular supply and thus obviated the need for surgery.
Regular monitoring of visual fields in patients with macroprolactinoma receiving
medical treatment is therefore important. Early recognition of secondary field
loss due to chiasmal herniation enables correction of the visual field loss by
manipulation of the medical therapy.
PMID- 11012581
TI - Gigantism due to growth hormone excess in a boy with optic glioma.
AB - True gigantism is rare in early childhood and is usually due to excess GH
secretion from a pituitary adenoma. We report a case in which the endocrine
abnormality is secondary to an optic glioma. Careful endocrine evaluation has
shown that GH peak amplitude was not increased but rather there was failure of GH
levels to suppress to baseline and a lack of pulsatility. There is no evidence of
a direct secretory role for the tumour and we postulate that the tumour is
affecting GH secretion through an effect on somatostatin tone. Specific tumour
therapy is not indicated for this patient in the absence of mass effect or visual
disturbance. The GH excess is being treated with somatostatin analogue
(Octreotide) and as he has developed precocious puberty he is also receiving long
acting GnRH analogue (Zoladex). This boy appears likely to have neurofibromatosis
type 1 (NF1) which raises the question of subtle GH excess in NF1 patients with
tall stature.
PMID- 11012582
TI - Cushing's syndrome in a 16 year old girl due to ectopic ACTH precursor production
from a pancreatic tumour.
PMID- 11012583
TI - Muscle mass and function in thyrotoxic patients before and during medical
treatment.
PMID- 11012584
TI - Muscle mass and function in thyrotoxic patients before and during medical
treatment
PMID- 11012585
TI - Management of nail psoriasis.
AB - Nail psoriasis is often difficult to cure, but may respond to a range of
different approaches used alone or together. As with treatment of psoriasis
affecting skin, relapse is common and therapies may need to be maintained or
repeated. The exact benefits of many of these treatments are not well documented
in the literature. Basic nail care is important and topical therapies represent
the main modality of treatment for the majority of cases. In severe nail disease,
where there is a hypertrophic element, injection therapy with triamcinolone may
be helpful. PUVA and other forms of radiation may be of benefit, but as with
systemic therapy, they are usually useful in the context of treatment of
psoriasis elsewhere on the body.
PMID- 11012586
TI - Cutaneous leishmaniasis.
AB - Leishmaniasis is a major World health problem, which is increasing in incidence.
In Northern Europe it is seen in travellers returning from endemic areas. The
protozoa is transmitted by sandflies and may produce a variety of clinical
syndromes varying from a simple ulcer to fatal systemic disease. This review
considers the management of simple cutaneous leishmaniasis. Patients usually have
a single ulcer which may heal spontaneously, requiring only topical, or no
treatment at all. Lesions caused by Leishmania braziliensis may evolve into the
mucocutaneous form, 'espundia', and should be treated with systemic antimony.
Sodium stiboglucoante 20 mg/kg/day i. v. for 20 days is the appropriate first
line treatment in these cases. Although it may cause transient bone marrow
suppression, liver damage, a chemical pancreatitis, and disturbances in the
electrocardiogram, it appears to be safe. The success of treatment should be
assessed 6 weeks after it has been completed and patients should be followed up
for 6 months.
PMID- 11012587
TI - General practitioner referral guidelines for dermatology: do they improve the
quality of referrals?
AB - Guidelines have proliferated in recent years in all areas of medicine, sometimes
with little evaluation of their effect. Referral guidelines for dermatology were
compiled by the dermatologist at the Royal Surrey County Hospital in consultation
with local general practitioners. An audit was undertaken to assess how
appropriate referrals were just before and after distribution of the guidelines
and was repeated 2 years later to determine whether they had made any significant
impact. The results revealed a 40% increase in the number of appropriate
referrals immediately after introduction of the guidelines, but this was not
sustained 2 years later. Five common conditions accounted for two-thirds of
inappropriate referrals before and after the guidelines were sent. The need for
continued general practitioner education in dermatology to reinforce referral
guidelines is demonstrated.
PMID- 11012588
TI - Erythema nodosum in Singapore.
AB - A retrospective study was carried out of all patients presenting with erythema
nodosum over a 3-year period (1994-1997) at the National Skin Centre, Singapore.
There were 75 patients, aged 4-70 years with a peak (40%) in the 21-30-year-old
age group; 65 were female and 10 were male, giving a female to male ratio of 6.5
: 1. Precipitating factors included viral respiratory tract infections and
streptococcal pharyngitis in 20 cases (26%), tuberculosis in two cases (3%),
pregnancy in three cases (4%) and miscellaneous conditions: Behcet's syndrome
(two cases), gonorrhoea (one case), varicella (one case) and cat-scratch disease
(one case). The cause was unknown in 45 cases (60%). The pattern of erythema
nodosum in Singapore is similar to that reported in the Western literature except
that sarcoidosis and inflammatory bowel disease are uncommon associations.
PMID- 11012589
TI - Multiple basal cell carcinomas and malignant melanoma following radiotherapy for
ankylosing spondylitis.
AB - We present the case of a 53-year-old Caucasian woman with seven basal cell
carcinomas and one malignant melanoma in situ along her back overlying her spine,
which was irradiated in 1968 for ankylosing spondylitis. These lesions developed
between 1997 and 1999. She has no other known risk factors for cutaneous
malignancy, in particular no history of excessive sun exposure. She has skin type
2. Molecular studies of glutathione S-transferase and cytochrome P450 status
showed her genotype not to constitute an overall increased inherited
susceptibility. We therefore postulate that all her skin cancers have arisen as a
consequence of her radiotherapy. To our knowledge this is the first case of
multiple basal cell carcinoma in addition to a malignant melanoma following
radiotherapy for benign disease.
PMID- 11012590
TI - Incipient osteomalacia occurring in chronic actinic dermatitis.
AB - Incipient osteomalacia developed in a Pakistani patient living in the UK after
strict sunlight avoidance forming part of the management of the photosensitivity
disorder, chronic actinic dermatitis. The patient's skin type and diet, which
included calcium-binding phytates in chappattis, had increased his risk of the
condition. Proximal muscle weakness and bony tenderness resulting from the
disorder resolved on vitamin D replacement therapy.
PMID- 11012591
TI - Chemotherapy-induced acral erythema: report of a case and immunohistochemical
findings.
AB - Chemotherapy-induced acral erythema (CAE) is an uncommon and distinct reaction
seen in patients receiving high-dose chemotherapy. The exact pathogenic
mechanisms of this disorder are still unknown. We report a 27-year-old woman who
presented with red, swollen and painful macules on both palms, clinically
consistent with this disease. Histological examination demonstrated vacuolar
degeneration of the basal cell layer and spongiotic blisters in the epidermis,
especially in the atrophied eccrine ducts and papillary oedema with mild
perivascular infiltration of mononuclear and hypersegmented neutrophils.
Immunohistochemistry showed that the infiltrating mononuclear cells were CD3
CD16+CD56+ leucocyte function antigen-1+, possibly natural killer cells. The
eccrine ducts expressed HLA-DR and intracellular adhesion molecule-1 (ICAM-1).
Our findings suggest that cell-to-cell interaction between NK cells and
keratinocytes in the eccrine apparatus may induce CAE and may be involved in the
pathogenesis of the skin reaction in our patient and possibly in this disease.
PMID- 11012592
TI - Calciphylaxis in the absence of renal failure.
AB - We report a patient with severe bilateral leg ulceration that was resistant to
treatment. A biopsy confirmed the cause as calciphylaxis. Calciphylaxis refers to
a syndrome of calcium deposition in the small and intermediate dermal vasculature
which can lead to epidermal ischaemia, ulceration and necrosis. Most cases occur
in those with chronic renal failure and secondary hyperparathyroidism. We
describe the rare presentation of calciphylaxis in a patient with normal renal
function and primary hyperparathyroidism who had many classical features.
Unfortunately she developed gangrene, sepsis and died.
PMID- 11012593
TI - Orificial tuberculosis and Kaposi's sarcoma in an HIV-negative individual.
AB - Orificial tuberculosis is a rare form of cutaneous tuberculosis. It happens
mainly in immunocompromised patients and is characterized by rapidly ulcerating
papules in the orifices, including oropharynx or anus, due to autoinoculation of
internal tuberculosis. It is a symptom of advanced underlying disease. Kaposi's
sarcoma occurs more frequently with the increase of HIV-infected patients. We
report on an HIV-negative individual who developed rapid-deteriorating orificial
tuberculosis concomitant with Kaposi's sarcoma and had a fatal outcome.
PMID- 11012594
TI - Dermatitis herpetiformis evolving into bullous pemphigoid: a probable example of
'epitope spreading'.
AB - We report a case of dermatitis herpetiformis which, 11 years after its original
diagnosis, evolved into bullous pemphigoid. Only a few similar cases supported by
immunofluorescence studies have been reported previously, and we believe that
they represent examples of 'epitope spreading', an increasingly recognized
phenomenon used to explain the coexistence of autoimmune diseases.
PMID- 11012595
TI - Co-existing actinic granuloma and giant molluscum contagiosum.
AB - Actinic granuloma of O'Brien and giant molluscum contagiosum in immunocompetent
adults are rare skin disorders. There have been no previous reports of these two
conditions occurring together. We report this occurrence in a 57-year-old
Caucasian woman.
PMID- 11012596
TI - Persistent annular erythema of infancy associated with intestinal Candida
colonization.
AB - We report a case of persistent annular erythema of infancy in a 4-month-old boy.
Physical and laboratory parameters showed no sign of internal disease or specific
infection except a massive Candida albicans colonization (> 103 organisms/mm3) of
the lower gastrointestinal tract. Oral treatment with amphotericin B for 2 weeks
resulted in a complete remission of the skin lesions indicating Candida
colonization as a trigger.
PMID- 11012597
TI - An unusual case of purpuric erythropoietic protoporphyria.
AB - Erythropoietic protoporphyria (EPP) is the most common of the erythropoietic
porphyrias. Recent advances in diagnostic laboratory tests have led to the
discovery of a number of previously undiagnosed cases. We describe a case of EPP
presenting late with a purpuric eruption and discuss the pathogenesis and
significance of purpura in EPP.
PMID- 11012598
TI - Rupioid psoriasis with arthropathy.
AB - A 31-year-old male presented with limpet-like, cone-shaped skin lesions on the
scalp, the extremities, and the trunk of 4 months' duration, and had had severe
joint pain in his right fingers, wrist, and knee for 1 month. Radiological
examination revealed arthritis of the above mentioned multiple joints. Rheumatoid
factor was serologically negative. Histopathological findings showed dense
inflammatory cell infiltration and remarkable Munro's microabscesses in the horny
layer in addition to psoriasiform epidermal hyperplasia, and predominant dermal
oedema. Based on clinicopathological findings, a diagnosis of rupioid psoriasis
with arthropathy was made. Following treatment for arthralgia using low doses of
systemic steroid, the effects of cyclosporin combined with topical steroids was
seen to alleviate dramatically the skin lesions and arthritis within 2 weeks.
There was no recurrence of such skin and joint lesions during a follow-up period
of 1 year.
PMID- 11012600
TI - Laser therapy of telangiectatic leg veins: clinical evaluation of the 810 nm
diode laser.
AB - Telangiectatic leg veins (TLV) are experienced by millions of women and men. As
they cause significant cosmetic embarrassment, many women seek effective
treatment. Options include sclerotherapy and treatment with different lasers. We
investigated the safety and efficacy of an 810-nm diode laser in the treatment of
TLV. Ten females had treatment to a >/= 25 cm2 area of TLV four times at 4-weekly
intervals at 25-35 W, 0.1 s duration, 0.5 s interval and a 5-mm circular spot
size (fluence of 12.7-17.8 J/cm2). Assessment of response was performed 4 weeks
after the final treatment and patients were asked to complete a questionnaire
requesting information regarding the treatment. No statistically significant
clearing of the leg veins was demonstrated although some improvement was noted in
individual patients. Side-effects were negligible, consisting of discomfort or
mild pain. There was no scarring, purpura or pigment alteration. A visual
analogue scale questionnaire (0-10) revealed that patients found the treatment
acceptable (range, 4-10). Overall difference as assessed by the patients ranged
from 0 to 8.4 and degree of satisfaction with the treatment from 0 to 9.8.
Currently, the treatment of choice for TLV remains sclerotherapy. Our results
suggest that the 810-nm diode laser is safe and well tolerated. Further research
could establish whether effectiveness can be improved with higher fluences or in
combination with sclerotherapy.
PMID- 11012599
TI - Langerhans cell migration.
AB - Epidermal Langerhans cells (LC) play pivotal roles in the induction of cutaneous
immune responses. Encounter with antigen in the skin, or other stimuli, cause the
mobilization of LC and their migration, via afferent lymphatics, to draining
lymph nodes where they localize within the paracortex. During their movement from
the skin LC acquire the characteristics of immunostimulatory dendritic cells (DC)
such that the antigen-bearing cells which accumulate in lymph nodes are able to
provoke specific T-lymphocyte responses. Epidermal cytokines initiate and
regulate LC migration (and maturation), of particular importance being
interleukin-1beta and tumour necrosis factor-alpha. Collectively, these
cytokines, together with relevant chemokine receptor-ligand interactions, effect
the liberation of LC from the epidermis and their directed movement to, and
localization within, peripheral lymph nodes. Described here are the phenotypic
changes induced during the activation of LC and the mechanisms through which
their migration is regulated.
PMID- 11012601
TI - Collagenase digestion and mechanical disaggregation as a method to extract and
immunophenotype tumour lymphocytes in cutaneous T-cell lymphomas.
AB - Various enzymatic or mechanical methods have been proposed in the past to
dissociate cells from different solid tissues. An automated mechanical
disaggregation device (Medimachine) has recently been proposed. Unfortunately,
most of these techniques are associated with a high cellular damage and a low
cell recovery and are difficult to apply to skin biopsies. In this paper, we
propose a combined enzymatic and mechanical method based on Medimachine, useful
for the isolation of skin infiltrating T-lymphocytes from small cutaneous
biopsies. As this method is easy and allows for a more correct qualitative and
quantitative cytofluorimetric analysis of the lymphocyte subsets, it may be
useful in the immunophenotyping of cutaneous T-cell lymphomas.
PMID- 11012602
TI - Do plasminogen activators play a role in lichen sclerosus?
AB - The histological changes of lichen sclerosus suggest that significant remodelling
of the extracellular matrix is occurring. As the proteases of the plasminogen
activator system have been implicated in tissue remodelling, cell migration and
tumour invasion, we performed an immunohistochemical study to look for evidence
of alteration in the expression of plasminogen/plasmin, urokinase-type
plasminogen activator, tissue-type plasminogen activator and alpha2-antiplasmin
in biopsies of clinically typical vulval lichen sclerosus obtained from 11
untreated adult women. Normal vulva obtained from gynaecological procedures and
samples of the patients' uninvolved thigh tissue were used as controls. No
significant difference was seen in the staining pattern between the lichen
sclerosus tissue and control tissue. However, although we found no
immunohistochemical evidence that the plasminogen activator system is involved in
the pathogenesis of vulval lichen sclerosus, it may be that other proteases are
involved.
PMID- 11012603
TI - Disaccharide analysis of skin glycosaminoglycans in atrophoderma of Pasini and
Pierini.
AB - There are divergent opinions as to whether atrophoderma of Pasini and Pierini
(APP) is a nosologic entity or a primary atrophic morphoea. In this study, we
used high performance liquid chromatography to analyse the skin disaccharide
contents of glycosaminoglycan (GAG) in two patients with APP and compared the
results with those from a typical atrophic morphoea patient. Perilesional
uninvolved skin was used as a control in each patient. In the atrophic phase
morphoea, both the total amount of disaccharide per skin punch-biopsy and the
amount of DeltaDi-4S(DS) - the main disaccharide unit of dermatan sulphate - per
mg dry weight were increased. These changes were consistent with sclerotic phase
morphoea. In contrast, the total amount of disaccharide per skin punch-biopsy was
decreased and the amount of DeltaDi-4S(DS) per mg dry weight was decreased or
unchanged in APP. Our results suggest that GAG metabolism in APP may be unique
and quite different from that in morphoea.
PMID- 11012604
TI - Heterozygous germline missense mutation in the p63 gene underlying EEC syndrome.
AB - Mutations in the p63 gene have recently been delineated as the molecular basis
for some cases of the ectrodactyly, ectodermal dysplasia and cleft lip/palate
(EEC) syndrome, an autosomal dominant disorder (MIM 129900). In this report, we
describe a 35-year-old woman with EEC syndrome and document a heterozygous
germline missense mutation, R304W, in exon 8 of the p63 gene. As with most other
p63 mutations in EEC syndrome, this mutation has arisen de novo and is located
within the core DNA-binding domain of p63. Identification of this mutation has
implications for genetic counselling and the feasibility of future DNA-based
prenatal diagnosis in this individual.
PMID- 11012605
TI - Dowling Oration 2000. Dermatology patients: what do they really need?
AB - Dermatology services must be organized to meet the needs of patients. These needs
change as society changes and medical knowledge increases. Considerable insight
into the true needs of individual and groups of patients can be gained from the
use of quality of life measures. Patients with widespread inflammatory skin
disease are most severely handicapped by their skin disease and can be most
helped by dermatology services. It is essential that such patients be given
priority in the delivery of dermatological care. Where necessary, protected
clinic time and specialist support services should be created to ensure that such
patients are not adversely affected by pressures to review patients in other
diagnostic groups.
PMID- 11012606
TI - PUVA therapy of granuloma annulare.
PMID- 11012607
TI - Are patients with localized nodular granuloma annulare more likely to have
diabetes mellitus?
PMID- 11012608
TI - Pemphigoid gestationis with intra-uterine death associated with foetal cerebral
haemorrhage in the mid-trimester.
PMID- 11012610
TI - Serological markers of disease activity in tuberculosis and HIV infection.
PMID- 11012611
TI - Pulmonary tuberculosis and serum IgE.
AB - Several recent studies indicate that mycobacterium or viral infection may reduce
IgE levels or suppress atopy or both. The present study was undertaken to
investigate whether Mycobacterium tuberculosis infection and its successful
treatment down-regulate serum total IgE levels, a marker of a Th2 response, due
to enhancement of a Th1 response in adult patients with tuberculosis (TB). We
prospectively studied the changes in serum total IgE and DTH response to
tuberculin, a marker of a Th1 response in 10 healthy controls, 20 patients with
pulmonary TB, and 19 asthma patients without TB. Measurement of serum total IgE
and tuberculin skin tests were performed before initiation of treatment and after
successful completion of 6 months treatment in TB patients, and at the
corresponding intervals in controls and asthmatics. The initial serum total IgE
concentrations were significantly higher in TB patients than in healthy controls
(282 +/- 26 U/ml (mean +/- s.e.m.) in TB patients versus 126 +/- 56 U/ml in
controls; P = 0.03). However, serum total IgE concentrations significantly
decreased (282 +/- 26 U/ml before versus 151 +/- 12 U/ml after treatment; P =
0.03) and tuberculin indurations significantly increased (23.6 +/- 1.8 mm before
versus 29.6 +/- 2.1 mm after treatment; P = 0.04) in TB patients. In contrast,
initial serum IgE concentrations and tuberculin indurations did not differ
significantly from post-observation data in both healthy controls and asthmatics
(P>0.30). The present study confirmed that immune responses to M. tuberculosis
down-regulate a Th2 immune response, and might contribute to the decreased
prevalence of allergic disorders.
PMID- 11012609
TI - Chronic granulomatous disease.
PMID- 11012612
TI - Atopic eczema is associated with delayed maturation of the antibody response to
pneumococcal vaccine.
AB - The aim of this study was to investigate a previously undocumented observation,
that children with atopic eczema under 9 years of age tended to have a poor
antibody response to Pneumococcal vaccination. Thirty-five children (mean age 8.8
years, range 3-16 years) with moderate to severe atopic eczema but no history of
systemic infection were studied retrospectively. Pneumococcal antibody responses
after immunization with Pneumovax II were compared with a hospital control group
consisting of 36 children (mean age 6.0 years, range 3-16 years) with recurrent
upper respiratory tract infections. Only 17% of children with atopic eczema aged
3-8 years responded to Pneumovax. This response was significantly poorer than
that of the controls (57%) (odds ratio 0.20, 95% confidence interval (CI) 0.05
0.84, P = 0.03). There were no significant differences in the levels of total
IgG2, the component of IgG associated with protective antibody responses to
Pneumococcus between the two groups. Delay in maturation of the total IgG and
IgG2 antibody response to Pneumococcus is a feature in this group of children
with moderately severe atopic eczema.
PMID- 11012613
TI - Role of caspases in dexamethasone-induced apoptosis and activation of c-Jun NH2
terminal kinase and p38 mitogen-activated protein kinase in human eosinophils.
AB - Eosinophils are the principal effector cells for the pathogenesis of allergic
inflammation. Glucocorticoids such as dexamethasone have long been used
therapeutically for eosinophilia in allergic inflammation by inducing eosinophil
apoptosis, but little is known about the intracellular mechanisms mediating
dexamethasone-induced apoptosis. In the present study, we investigated the effect
of dexamethasone on three mitogen-activated protein kinases (MAPK) involved in
the intracellular signalling pathway: c-Jun NH2-terminal kinase (JNK), p38 MAPK
and extracellular signal-regulated kinase (ERK). We found that dexamethasone
could activate JNK and p38 MAPK in a time-dependent manner but not ERK. Further,
SB 203580, a specific p38 MAPK inhibitor, was additive with dexamethasone in
inducing eosinophil apoptosis, while JNK1/2 antisense phosphorothioate
oligodeoxynucleotides did not show any significant effect. These suggest that
dexamethasone-induced JNK1/2 and p38 MAPK activation are not crucial to the
induction of apoptosis. Pretreatment of eosinophils with benzyloxycarbonyl-Val
Ala-Asp-fluoromethylketone (Z-VAD.FMK), a broad-spectrum caspase inhibitor, could
inhibit dexamethasone-induced apoptosis in eosinophils dose-dependently.
Moreover, Z-VAD.FMK partially inhibited dexamethasone-activated JNK and p38 MAPK
activities. However, dexamethasone treatment did not activate specific caspase-3,
-8 activity in eosinophils compared with spontaneous apoptosis. We therefore
conclude that dexamethasone-induced apoptosis and activation of JNK and p38 MAPK
activity in eosinophils are regulated by caspases but not through the common
apoptosis-related caspase-3, -8 as in other cell types. Elucidation of the
important role of caspases in eosinophil apoptosis may facilitate the development
of more specific and effective treatment for allergic inflammation.
PMID- 11012614
TI - Effects of IL-4 and IL-12 on experimental immune-mediated blepharoconjunctivitis
in Brown Norway rats.
AB - IL-12 and IL-4 are critical cytokines for Th1 and Th2 differentiation,
respectively. To assess the roles of these cytokines in the development of
experimental immune-mediated blepharoconjunctivitis (EC) in Brown Norway (BN)
rats, their effects were tested either in vitro or in vivo. Draining lymph node
cells from rats immunized with ragweed pollen (RW) in Al(OH)3 were collected and
cultured for 3 days with RW in the presence of IL-4, IL-12, or PBS as a control.
After harvesting the culture supernatants for cytokine ELISA and the cells for
cytokine reverse transcriptase-polymerase chain reaction, 10 million cells were
injected intravenously into syngeneic recipient rats (n = 12 per group). The rats
were challenged with RW by eye drops 4 days after transfer. Eyes were harvested
for histology 24 h later. Furthermore, IL-12 (500 ng per injection) or PBS was
injected intraperitoneally every other day seven times from the day of active
immunization (n = 6 per group). One day after the last injection, rats were
challenged and EC was evaluated as above. Transfer of cells with IL-4 in vitro
augmented eosinophilic infiltration in the conjunctiva compared with the other
two groups, whereas IL-12 in vitro suppressed eosinophilic infiltration and
increased lymphocytic infiltration. Interferon-gamma production was augmented by
IL-12. IL-4 RNA expression was augmented by IL-4. IL-12 administration in vivo
augmented lymphocytic infiltration in the conjunctiva without affecting
infiltration of eosinophils. In conclusion, IL-4 and IL-12 either in vitro or in
vivo augmented Th2 and Th1 immunity, respectively, thus leading to distinct
histological features of EC.
PMID- 11012615
TI - Eosinophil granule-derived major basic protein induces IL-8 expression in human
intestinal myofibroblasts.
AB - Eosinophil infiltration occurs in a variety of allergic and inflammatory
diseases. The release of preformed mediators from eosinophils may contribute to
inflammatory responses. We investigated the ability of eosinophil-derived major
basic protein and eosinophil-derived neurotoxin to stimulate production of IL-8
from intestinal myofibroblasts. Intestinal myofibroblasts (18-Co cells) were
incubated with major basic protein, eosinophil-derived neurotoxin, or a synthetic
analogue of major basic protein, poly-L-arginine. Immunoreactive IL-8 was
measured by ELISA and IL-8 mRNA levels were analysed by Northern blot or reverse
transcription-polymerase chain assay. Major basic protein induced IL-8 mRNA
production and release of significant levels of IL-8 immunoreactive protein. By
contrast, eosinophil-derived neurotoxin stimulated little IL-8 release. The
induction of IL-8 mRNA by poly-L-arginine was significantly inhibited by
actinomycin D. These findings demonstrate a novel interaction between eosinophils
and intestinal fibroblasts that may be involved in the pathogenesis of diseases
associated with tissue eosinophilia.
PMID- 11012616
TI - Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC)
of healthy controls.
AB - IL-17 is a T cell cytokine with a complex and important role in the immune
system. It has been detected in rheumatoid arthritis (RA) synovial membrane and
found to stimulate the production of the proinflammatory cytokines IL-6, IL-8,
tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony
stimulating factor (GM-CSF) in vitro. To date, there are few data available on
the agents that stimulate IL-17 production. We therefore investigated the in
vitro IL-17 response to a variety of mitogens and antigens, and compared the IL
17 response to interferon-gamma (IFN-gamma), IL-4, IL-10 and TNF-alpha. In this
study we used a type-0 antigen, tetanus toxoid (TT), a type-1 antigen, PPD from
Mycobacterium tuberculosis, a potential type-2 rye grass (RG) antigen (Lol I) and
an autoantigen SS.B (La), to stimulate PBMC from healthy controls. Cytokine mRNA
was measured using semiquantitative reverse transcriptase-polymerase chain
reaction and cytokine protein measured using specific ELISA techniques, while the
frequency of IL-17-producing T cells was determined by flow cytometry. The
mitogens concanavalin A, phytohaemagglutinin and phorbol myristate
acetate/ionomycin induced a significant increase in IL-17, with the highest
levels being produced by anti-CD3/anti-CD28 stimulation. The antigens TT and PPD
significantly increased IL-17 mRNA expression over time, but failed to have such
an effect at the protein level. IL-17 protein was also detectable in both antigen
specific (TT, SS. B) and non-specific T cell clones, but at levels lower than IFN
gamma. IL-17 production did not correlate with either the type-1 cytokine IFN
gamma or TNF-alpha or the type-2 cytokine IL-4 or IL-10 at either the mRNA or
protein level.
PMID- 11012617
TI - Glycosylphosphatidylinositol (GPI)-deficient Jurkat T cells as a model to study
functions of GPI-anchored proteins.
AB - Many cell surface proteins attached to the membrane by GPI are involved in cell
signalling. However, the role of the GPI membrane anchor itself remains poorly
understood. GPI-defective cells from patients with paroxysmal nocturnal
haemoglobinuria (PNH) are relatively resistant to apoptosis induction. We
developed a Jurkat T cell model for GPI deficiency by isolating a GPI-negative
mutant, which is defective in the GPI biosynthetic gene PIG-A. Using retroviral
PIG-A gene transfer along with the transfer of a vector control, we obtained two
genetically identical cell lines, distinguished only by expression of the PIG-A
gene and, thus, their ability to produce GPI. Cell proliferation and survival
were not affected by this difference. Apoptotic stimuli such as serum starvation
and camptothecin exposure elicited similar responses. In contrast, GPI-defective
Jurkat cells were more susceptible to Fas-mediated apoptosis than GPI-positive
cells. These results indicate that a deficiency in GPI-anchored proteins, as is
found in PNH, does not confer resistance to apoptosis.
PMID- 11012618
TI - Antibodies, directed towards Campylobacter jejuni antigens, in sera from poultry
abattoir workers.
AB - Occupational exposure of susceptible humans to Campylobacter jejuni appears to
result in resistance to disease. This is believed to be due to acquired
protective immunity. To support this hypothesis the levels of C. jejuni-specific
IgG and IgM antibodies were determined in sera from poultry abattoir workers.
Such individuals are persistently exposed to C. jejuni, but apparently rarely
acquire campylobacteriosis. Sera from 43 short-term workers (employed < or = 1
month), 78 long-term workers and 40 blood donors were investigated by ELISA. In
51 individuals a second serum sample, taken at least 1 month after the first, was
also investigated. Eight workers had C. jejuni-positive faecal cultures and only
one, a short-term worker, had symptoms of campylobacteriosis. There were
significantly higher levels of specific IgG antibodies in long-term workers than
in either of the other groups. There was no significant difference detectable in
specific IgM antibody levels between any of the groups. The results provide
supporting evidence that long-term exposure to C. jejuni induces circulating
antibodies which reflect apparent reduced susceptibility to disease. Western
blotting showed flagellin and polypeptides of 45, 40, 32 and 30 kD bound
antibodies significantly more frequently by sera from long-term workers than
short-term workers and blood donors. The most commonly detected antigens were the
40-kD (80%) and flagellin (55%). The results indicate that specific serum IgG
responses induced by endemic exposure to C. jejuni might be directed towards a
small number of protein antigens with apparently conserved epitopes.
PMID- 11012619
TI - Induction of necrosis and apoptosis of neutrophil granulocytes by Streptococcus
pneumoniae.
AB - Apoptosis followed by macrophage phagocytosis is the principal mechanism by which
neutrophil granulocytes (PMN) are removed from the site of inflammation. To
investigate whether Streptococcus pneumoniae causes apoptosis of PMN, we exposed
PMN to viable and heat-killed pneumococci and purified pneumococcal cell walls
(PCW). The occurrence of PMN cell death was quantified by flow cytometry using
annexin V/propidium iodide labelling of the cells. Intracellular histone
associated DNA fragments were quantified by ELISA. The presence of apoptosis was
confirmed by in situ tailing. Exposure of PMN to viable pneumococci caused
necrosis of the cells. The pneumococcal cytotoxin pneumolysin, the bacterial
production of hydrogen peroxide, and PCW contributed to necrosis. Heat-killed
pneumococci accelerated the process of apoptosis observed in cultivated non
stimulated PMN in vitro. These results demonstrated that pneumococci induce PMN
cell death. Depending on the intensity of the stimulus, PMN necrosis and
apoptosis were observed.
PMID- 11012620
TI - Intrapulmonary concentrations of inflammatory cytokines in a mouse model of
chronic respiratory infection caused by Pseudomonas aeruginosa.
AB - We investigated the role of inflammatory cytokines in a mouse model of chronic
Pseudomonas aeruginosa infection mimicking diffuse panbronchiolitis (DPB), and
determined the effects of clarithromycin therapy on the production of these
cytokines. The concentrations of IL-1beta, IL-2, IL-4, IL-5, interferon-gamma
(IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were measured serially
in the lungs of mice with experimentally induced chronic respiratory P.
aeruginosa infection until 60 days after inoculation. The concentrations of these
cytokines during the course of the disease were significantly higher than
baseline (before inoculation, P<0.01 for all cytokines). Clarithromycin
significantly inhibited the production of IL-1beta and TNF-alpha in the lung
(P<0.01). The same treatment also reduced the levels of other cytokines, albeit
insignificantly. Treatment with anti-TNF-alpha antibody significantly reduced the
number of pulmonary lymphocytes and concentration of IL-1beta in the lung
(P<0.01), but did not change the number of viable bacteria. Our findings resemble
those detected in bronchoalveolar lavage fluid of patients with DPB and indicate
that inflammatory cytokines play an important role in chronic P. aeruginosa lung
infection. Our results also show that macrolides modulated the production of
these cytokines, ultimately reducing lymphocyte accumulation in the lung. Our
data suggest that anti-TNF-alpha antibody might be a useful new strategy for the
treatment of chronic respiratory P. aeruginosa infection.
PMID- 11012622
TI - Tuberculosis (TB) and HIV infection are independently associated with elevated
serum concentrations of tumour necrosis factor receptor type 1 and beta2
microglobulin, respectively.
AB - The aim of this study was to identify immune markers that are independently
associated with HIV infection or TB in vivo. Using commercially available assays,
we measured concentrations of five immune markers in sera from 175 out-patients
attending medical clinics in Cote D'Ivoire and Ghana, West Africa. Patients were
categorized into groups with TB only (TB+HIV-, n = 55), TB and HIV co-infection
(TB+HIV+, n = 50), HIV infection only (TB-HIV+, n = 35), or neither infection (TB
HIV-, n = 35). TB+HIV+ and TB-HIV+ groups were matched for blood CD4+ lymphocyte
count. Mean +/- s.d. concentrations of beta2-microglobulin were similarly
increased in both the TB-HIV+ (5.3+/-2.1 microg/ml, P<0.0001) and the TB+HIV+
(5.0+/-1.5 microg/ml, P<0.0001) groups compared with the TB-HIV- group (2.2+/-1.8
microg/ml), but were only slightly increased in the TB+HIV- group (3.2+/-1.8
microg/ml, P = 0.01). In contrast, mean serum concentrations of soluble tumour
necrosis factor receptor type I (sTNF-RI) were similarly elevated in the TB+HIV-
(1873+/-799 pg/ml, P<0.0001) and TB+HIV+ (1797+/-571 pg/ml, P<0.0001) groups
compared with uninfected subjects (906+/-613 pg/ml), but there was only a small
increase in sTNF-RI in the TB-HIV+ group (1231+/-165 pg/ml, P = 0.03). Both TB
and HIV infection were associated with substantial elevation of serum
concentrations of soluble CD8, soluble CD54, and sTNF-R type II. Analysis of
additional samples from groups of TB+HIV- and TB+HIV+ patients receiving anti-TB
treatment showed significant and equal reductions in mean serum sTNF-RI
concentrations, but no significant change in mean beta2-microglobulin. Thus,
serum beta2-microglobulin and sTNF-RI serve as relatively independent markers of
HIV infection and TB, respectively, in studies of co-infected persons.
PMID- 11012621
TI - A single measurement of CD38CD8 cells in HIV+, long-term surviving injecting drug
users distinguishes those who will progress to AIDS from those who will remain
stable.
AB - This study compares the predictive power of a single measurement of CD8+CD38+,
CD8+CD45RO+ or CD8+CD38+CD45RO+ subpopulations in predicting progression to AIDS
in a cohort of HIV+ long-term surviving injecting drug users. The results showed
that both the total CD8+ percentage, and the CD8+CD38+ and CD8+CD38+CD45RO+
subpopulations of cells all individually predicted progression to AIDS. In
combination with CD4, only the CD8+CD38+ subpopulation enhanced the predictive
power of the CD4 percentage alone. The CD8+ percentage correlated negatively with
the CD4 percentage and the CD8+CD45RO+ subpopulation did not predict disease
progression. The proportion of CD8+CD38+ cells identified which patients with a
moderate CD4 level were more likely to progress to AIDS, and conversely, which
patients with a low CD4 count were likely to remain clinically stable. The
results were consistent irrespective of whether time was measured from the date
of seroconversion, or from the date of the test. This study is the first to
measure these markers in HIV-infected injecting drug users, and in long-term
survivors. The results demonstrate the considerable added value of the CD8+CD38+
cell percentage over the CD4 count alone, in predicting HIV clinical progression.
PMID- 11012623
TI - Efficient generation of respiratory syncytial virus (RSV)-neutralizing human
MoAbs via human peripheral blood lymphocyte (hu-PBL)-SCID mice and scFv phage
display libraries.
AB - RSV is one of the major causes of pneumonia and bronchiolitis in infants and
young children and is associated with high mortality. RSV neutralizing human
antibody (hu-Ab) is known to mediate resistance to viral infection as well as to
be an effective treatment for severe lower respiratory tract RSV infection. We
have previously demonstrated that human primary and secondary immune responses
can be established in severe combined immunodeficient mice engrafted with human
peripheral blood lymphocytes (hu-PBL-SCID). By combining this animal model with
the single-chain Fv antibody (scFv) phage display library technique, we were able
to investigate further its clinical potential by generating a panel of human
scFvs that exhibit both high F glycoprotein (RSV-F) binding affinities (
approximately 108 M(-1)) and strong neutralizing activities against RSV infection
in vitro. Sequencing analysis of the randomly isolated anti-RSV-F scFv clones
revealed that they were derived from different VH families with mutations in the
complementarity-determining region 1 (CDR1). The results suggest that: (i) RSV-F
specific human immune responses and affinity maturation can be induced in hu-PBL
SCID mice; and (ii) this approach can be applied to generate large numbers of
human scFvs with therapeutic potential. Despite the fact that hu-PBL-SCID mouse
and human scFv phage display library have individually been established, our
approach contributes a simple and significant step toward the generalization of
antigen-specific human monoclonal antibody (hu-MoAb) production and their
clinical applications.
PMID- 11012624
TI - Influence of age and HLA type on interferon-gamma (IFN-gamma) responses to a
naturally occurring polymorphic epitope of Plasmodium falciparum liver stage
antigen-1 (LSA-1).
AB - Antigenic polymorphism and HLA restriction may limit the immunogenicity of a
subunit vaccine against liver-stage Plasmodium falciparum. We examined 59
clinical isolates and five laboratory clones of P. falciparum for polymorphism in
the N- and C-terminal regions of LSA-1, evaluated binding of the corresponding
peptides to selected HLA class I alleles, and measured IFN-gamma responses in
residents of a malaria-endemic area of Papua New Guinea where HLA-A*1101, -24,
B13, and -B40 are the most common class I alleles. LSA-1 polymorphism was limited
to a single non-synonymous mutation encoding serine (S), proline (P), or
threonine (T) at amino acid 85. Nine-mer 84-92 peptides with S, T, or P at the
primary anchor position bound differentially to HLA-A11, -A2, and -B7. IFN-gamma
ELISPOT responses increased with age in malaria-exposed subjects: 14-16% and 30
36% of 2-5- and 6-54-year-olds, respectively, had > or =10 IFN-gamma-secreting
cells/106 peripheral blood mononuclear cells when stimulated with at least one
peptide variant (P<0.05). IFN-gamma responses to all three peptides were also
greater for older than younger individuals. No children < 3 years old had
lymphocytes that responded to all three 84-92 peptides, whereas 45% of adults
(mean age 48 years) had aggregated IFN-gamma responses. These data support the
notion that age-related cumulative exposure to P. falciparum increases the
frequency of IFN-gamma responses to polymorphic epitopes of liver-stage antigens
such as LSA-1.
PMID- 11012625
TI - Humoral hyporesponsiveness to a conjugate contraceptive vaccine and its bypass by
diverse carriers using permissible adjuvant.
AB - A contraceptive vaccine directed against human chorionic gonadotropin (hCG) has
previously undergone clinical testing that demonstrated the feasibility of the
approach in preventing pregnancy in women. Some immunized volunteers however, did
not respond with an adequate anti-hCG antibody response despite employing highly
immunogenic bacterial toxoids as carriers. Since there is some evidence that T
cell responses to a complex protein typically focus on a few immunodominant
epitopes, we investigated the responsiveness to hCG in mice of different
haplotypes using the protein carrier diphtheria toxoid (DT). Our data showed a
differential carrier effect of DT. With the aim of making a more potent immunogen
employing promiscuous pathogen-derived Th peptides as carriers, peptide:antigen
stoichiometric ratios were optimized. When tested individually using alum as the
adjuvant, three such peptide conjugates improved the anti-hCG response, though
not consistently to levels higher than the DT conjugate. Immunization with a
combination of these synthetic epitopes generated anti-hCG responses higher than
those achieved with DT or with the individual peptides. Antibodies were of high
affinity and capable of neutralizing the bioactivity of hCG, but were devoid of
anti-peptide reactivity. These results support our view that differential
hyporesponsiveness in a diverse population may arise from inadequate carrier
effect and that it can be overcome by use of pathogen-derived broadly reactive
non-B Th epitopes employing only alum, a permissible adjuvant.
PMID- 11012626
TI - Local bioactive tumour necrosis factor (TNF) in corneal allotransplantation.
AB - The aim of this study was to examine the kinetic profile of bioactive TNF levels
in aqueous humour of rabbit eyes undergoing corneal allograft rejection and to
investigate the effect of locally blocking TNF activity after corneal
transplantation. In a rabbit corneal transplantation, endothelial allograft
rejection was identified and correlated with increase in central graft thickness.
Samples of aqueous humour obtained on alternate days following transplantation
were tested for TNF mRNA and bioactive TNF protein. To investigate the effect of
locally blocking TNF activity in allograft recipients, the fusion protein TNFR-Ig
was administered by injections into the anterior chamber after transplantation.
Pulsatile increases in levels of this cytokine were found in 14 of 15 allograft
recipients. Peaks of TNF bioactivity preceded by varying intervals the observed
onset of rejection in allograft recipients. TNF levels were not elevated in
aqueous humour from corneal autograft recipient controls or in serum of
allografted animals. mRNA levels were elevated before onset of and during
clinically observed allograft rejection. In three of seven animals receiving TNFR
Ig injections on alternate days from day 8 to day 16 post-transplant, clear
prolongation of corneal allograft survival was demonstrated. Bioactive TNF is
present in aqueous humour following rabbit corneal allotransplantation. Rather
than correlating directly with endothelial rejection onset, pulsatile peak levels
of TNF precede and follow the observed onset of endothelial rejection. Blockade
of TNF activity prolongs corneal allograft survival in some animals, indicating
that this cytokine may be a suitable target in local therapy of corneal allograft
rejection.
PMID- 11012627
TI - Antigen-specific T cell responses in human peripheral blood leucocyte (hu-PBL)
mouse chimera conditioned with radiation and an antibody directed against the
mouse IL-2 receptor beta-chain.
AB - A weakness of the hu-PBL-SCID model for the study of human immune functions is
the appearance of anergy and the consequent loss of T cell function. We
demonstrate here that human T cells retain normal functions during the early
stage of chimerism. At 1 and 2 weeks post-engraftment, T cells isolated from the
peritoneal cavity of hu-PBL chimeras could be activated and proliferated upon
stimulation with phytohaemagglutinin (PHA) or specific antigens to which the cell
donor was known to be immune. T cells derived from hu-PBL-SCID and hu-PBL
NOD/LtSz-scid (NOD/SCID) mice not only proliferated but also produced interferon
gamma (IFN-gamma) and IL-5 following in vitro stimulation with tetanus toxoid
(TT) or hepatitis B surface antigen (HBsAg). These antigen-specific T cells could
only be demonstrated when cognate antigen was administered together with or
immediately following the PBL transfer. Without an early rechallenge with antigen
in vivo, no TT- or HBsAg-specific T cell responses could be elicited, showing the
vulnerability and antigen-dependence of the T cell response. Vigorous anti-TT or
anti-HBs responses could be observed in all chimeras. Administration of antigen
together with the PBL graft enhanced the humoral anti-TT response in SCID and
NOD/SCID mice but had little effect on the anti-HBs antibody response in NOD/SCID
mice. These data confirm the observation that the B cell compartment in hu-PBL
SCID chimera is largely antigen-independent and extend this to SCID/NOD.
PMID- 11012628
TI - A pivotal role of cell-bound but not soluble CD4 molecules in full development of
lupus-like manifestations in MRL-Fas(lprcg)/Fas(lprcg) mice.
AB - The role of CD4 molecules in the autoimmune and lymphoproliferative syndrome
caused by murine Fas mutations was studied using the novel systemic lupus
erythematosus (SLE) model, MRL-Fas(lpr(cg))/Fas(lprcg) (MRL-lpr(cg)) mice, in
combination with the novel mutant CD4 gene producing soluble CD4 (sCD4) instead
of membrane-bound CD4 (mCD4). For this purpose, various autoimmune manifestations
were compared among MRL-lpr(cg) mice homozygous (CD4slprcg), heterozygous
(CD4s/mlpr(cg)), and wild-type (CD4mlpr(cg)) for the CD4 mutation. The mortality,
glomerulonephritis, proteinuria, and lymphadenopathy were significantly
ameliorated in CD4slprcg compared with CD4mlpr(cg) and CD4s/mlpr(cg) mice, both
being comparable in these clinical characteristics. In parallel with the clinical
improvement, the serum levels of immunoglobulin, anti-DNA antibodies, anti
nuclear antibodies and immune complexes, and the extent of glomerular immune
deposition, were significantly lower in the former. The results indicate that
mCD4 is important and can not be replaced by sCD4 in full development of SLE-like
manifestations, and suggest that CD4+ T cells may aggravate the autoimmune
disease by stimulating autoreactive B cells to produce autoantibodies through
their helper activity in Fas mutant models. The sCD4 levels in the serum and
spleen elevated with the increased accumulation of B220+CD4-CD8- (double-negative
(DN)) T cells in CD4slpr(cg) mice. This, together with the significantly milder
lymphadenopathy associated with lower DN T cell contents in CD4slpr(cg) than
CD4mlpr(cg) mice, implies that some of abnormal DN T cells may be derived from
cells of the CD4 lineage.
PMID- 11012630
TI - Methods for the detection of blood parasites.
PMID- 11012629
TI - Tumour necrosis factor-alpha (TNF-alpha) enhances lymphocyte migration into
rheumatoid synovial tissue transplanted into severe combined immunodeficient
(SCID) mice.
AB - Adhesion mechanisms play a major role in the recruitment of peripheral blood
lymphocytes (PBL) which characteristically infiltrate rheumatoid arthritis (RA)
synovium and other chronically inflamed tissues. Through a sequential series of
complex integrated adhesion and signalling events, 'multistep model of
migration', specific subsets of PBL are recruited into inflamed tissues. In this
process both leucocyte receptors and microvascular endothelial (MVE) counter
receptors play a critical role. The MVE in particular, during an inflammatory
state, is the target of various inflammatory mediators that cause the up
regulation of several cell adhesion molecules (CAM). One of the most important
factors known to be a powerful inducer of MVE CAM is TNF-alpha. Conversely,
blocking TNF-alpha causes a down-modulation of CAM expression. To test directly
the capacity of TNF-alpha to induce cell migration into RA synovium we adapted a
model in which synovial grafts were implanted into SCID mice subcutaneously.
Using this model we demonstrate that: (i) transplants remain viable and become
vascularized and fed by mouse subdermal vessels; (ii) the mouse vasculature
connects to the transplant vasculature which maintains the ability to express
human CAM; (iii) intragraft injections of TNF-alpha up-regulate the expression of
human CAM, following the down-regulation which occurred 4 weeks post
transplantation; and (iv) the up-regulation of graft CAM is associated with
increased human PBL migration into the transplants. This study provides direct
evidence in vivo of the capacity of TNF-alpha to induce cell migration. In
addition, it provides the experimental background for the optimal use of this
model.
PMID- 11012631
TI - Automated counting of white and red blood cells in the cerebrospinal fluid.
AB - The objective of this study was to examine to what extent the automated method of
the Bayer H*2 instrument could replace the visual counting of white and red blood
cells in cerebrospinal fluid. The number of white blood cells as well as the
percentage of mononuclear and polymorphonuclear cells were counted in the 'Baso
channel' (Research screen 3) whereas the number of red cells were registered as
the 'R-count' (Research screen 1). All automated cell counts were compared to
visual estimates. The automated count yielded reliable results down to 5 x 106
white blood cells/l and 5 x 108 red blood cells/l. In some samples 'noise' was
present in the Baso channel. A correct white blood cell count could then be
obtained by counting the cells directly as dots on the screen. It was possible to
differentiate between polymorphnuclear cells and mononuclear cells at all WBC
concentrations. The automated counting of cerebrospinal fluid can be performed
without changing thresholds or sample volumes of the instrument. Thus, in the
routine practice it will be possible to alternate between automated counting of
whole blood samples and cerebrospinal fluid samples.
PMID- 11012632
TI - Two colour analysis of reticulated platelets.
PMID- 11012633
TI - Angiocentric nasal T/natural killer cell lymphoma: a single centre study of
prognostic factors in 108 patients.
AB - Angiocentric T cell/natural killer (NK) nasal lymphoma remains a rare clinical
presentation in North America and Europe but is more common in Asia and Latin
America. We have reviewed 108 cases of angiocentric T/NK cell lymphoma of the
nasal cavity with a view to establishing prognostic factors. Most patients were
high or high intermediate clinical risk and had additional poor prognostic
factors such as bulky disease, high levels of beta 2 microglobulin, advanced
stage and multiple extranodal involvement. At 8 years, overall survival was 82%,
90% and 84% for low-intermediate, high-intermediate and high clinical,
respectively. Disease free survival was very similar: 79%, 83% and 80%,
respectively. Multivariate analysis did not identify any factor influencing
overall survival and disease-free survival. There was no evidence that the
international prognostic index (IPI) was applicable in these patients and it
appears that angiocentric T/NK cell lymphoma is an independent prognostic factor
itself.
PMID- 11012634
TI - Severe iron deficiency anaemia and stroke.
AB - Neurological complications of severe anaemia in childhood are rare. We report a
case of severe iron deficiency in a child of 23 months, presenting as an acute
hemiparesis.
PMID- 11012635
TI - Efficacy of low dose intravenous immunoglobulins for post-splenectomy treatment
of autoimmune haemolytic anaemia in a patient with hereditary spherocytosis.
AB - Summary Idiopathic autoimmune haemolytic anaemia developed in a patient with
hereditary spherocytosis. The behaviour of some osmotic fragility tests
throughout the illness and the efficacy of intravenous immunoglobulins in
controlling autoimmune haemolysis which recurred post splenectomy are discussed
PMID- 11012636
TI - The cutaneous side-effects of hydroxyurea.
AB - The cutaneous side-effects of long-term hydroxyurea therapy are not widely known
and only rarely reported. We report on a patient who developed widespread skin
changes, including the recently recognized hydroxyurea dermopathy, during long
term treatment with hydroxyurea for polycythaemia rubra vera. The time course of
the clinical changes suggests that they result from direct toxicity of
hydroxyurea on the basal layer of the epidermis and mucosal surfaces. We aim to
increase clinical awareness of this problem.
PMID- 11012637
TI - Acute myeloid leukaemia with trilineage myelodysplasia complicated by masked
diabetes insipidus.
AB - We describe a rare case of acute myeloid leukaemia with trilineage myelodysplasia
complicated by central diabetes insipidus. In the present case, diabetes
insipidus was masked by corticosteroid deficiency due to hypopituitarism and
clinical symptoms presented after administering methylprednisolone. Although the
remission of leukaemia was not achieved by chemotherapy, excessive urinary output
was well-controlled by nasal administration of 1-desamino-8-D-arginine
vasopressin (DDAVP) during the course.
PMID- 11012638
TI - Natural killer-cell lymphocytosis and strongyloides infection.
AB - We report a case of strongyloides infection in a 72-year-old man presenting with
acute angio-oedema and urticaria. He was also found to have natural killer cell
(NK) large granular lymphocytosis (LGL). We discuss the possible relationship
between the strongyloides infection and the NK-LGL lymphocytosis.
PMID- 11012639
TI - Multiple myeloma and immune thrombocytopenia.
AB - Immune thrombocytopenia (ITP) is frequently encountered in patients with
lymphoproliferative disorders. However this is only rarely reported in patients
with multiple myeloma. We describe three cases who presented initially with the
clinical manifestations of ITP but were subsequently found to have multiple
myeloma. Platelet count increments to standard treatment modalities for ITP were
observed in all three patients with transient or partial response. The importance
of recognizing the immune mediated thrombocytopenia in patients with myeloma and
the implications of this combination are discussed.
PMID- 11012640
TI - Laboratory findings associated with thrombophilia are not more common in
inflammatory bowel disease.
AB - Thromboembolic disease (TED) has been recognized as a complication of
inflammatory bowel disease (IBD) since the 1930s (Bargen & Barker 1936). The
relative contributions of inherited or acquired thrombophilia and the
inflammatory response to the mechanism of this tendency is unclear. Thrombotic
events are more common in active disease although significant numbers also occur
spontaneously, when the disease is in clinical remission (Talbot et al. 1986;
Jackson et al. 1997). Studies looking at the prevalence of specific thrombophilic
states such as Antithrombin III deficiency (Jackson et al. 1997; Lake, Stauffer &
Stuart 1978; Cianco et al. 1996; Ghosh et al. 1983), Factor V Leiden mutation
(APC Resistance) (Jackson et al. 1997; Probert et al. 1997; Ardizzone et al.
1998; Liebman et al. 1998), anticardiolipin antibodies (Ciancio et al. 1996),
Protein C (Wyshock, Caldwell & Crowley 1988; Korsten & Reis 1992) and Protein S
deficiencies (Jorens et al. 1990; Aadland et al. 1992) in IBD have been
contradictory or equivocal. We had previously found that IBD patients with a
history of TED are not more likely to have a laboratory thrombophilic abnormality
than those with uncomplicated disease. We also demonstrated that the prevalence
of heterogenous laboratory thrombophilic abnormalities (usually minor) in all IBD
patients may be as high as 60%, much higher than the recognized prevalence of TED
(Lim, Jones & Gould 1996). We wondered how this would compare with the healthy
non-IBD population. We have therefore explored the prevalence of such
thrombophilic abnormalities in a group of IBD patients who had no history of TED
and compared them with healthy age and sex matched controls.
PMID- 11012641
TI - Thromboembolism in a patient with transient eosinophilia and thrombocytopenia.
AB - A 24-year-old woman with an unremarkable medical history who developed bilateral
deep venous thrombosis and pulmonary emboli is presented. Associated findings
were severe eosinophilia and moderate thrombocytopenia. Since the major acquired
and hereditary thrombogenic disorders were ruled out in this case (including
antiphospholipid syndrome and heparin-induced thrombocytopenia), we believe that
the severe eosinophilia per se could be the pro-coagulant factor leading to
thrombosis and embolism in our patient. The role of eosinophilia in thrombosis is
discussed.
PMID- 11012642
TI - More effective ways of health care service delivery in the UK.
PMID- 11012643
TI - The nose and nitric oxide: a review.
PMID- 11012644
TI - Paediatric airway stenosis: laryngotracheal reconstruction or cricotracheal
resection?
AB - Modern surgical management of paediatric laryngotracheal stenosis includes a wide
variety of surgical procedures. These can broadly be divided into two groups.
First, laryngotracheal reconstruction (LTR) procedures in which the cricoid
cartilage is split and the framework is expanded with various combinations of
cartilage grafts and stents; and second, cricotracheal resection (CTR) where a
segmental excision of the stenotic segment is done and an end-to-end anastomosis
is performed. In this article we review the literature and our experience and
discuss the relative indications for CTR and LTR in children. High decannulation
rates have been reported for CTR; however, it remains a more extensive procedure
than LTR involving extensive tracheal mobilization. If the tracheostomy site is
included in the resection then a significant length of trachea is excised.
Alternatively, LTR with cartilage grafting can precisely correct a specific
stenosis with minimum morbidity and high decannulation rates for grade 2 and
selected grade 3 stenosis. For the more severe stenosis treatment with LTR has
been less successful. Retrospective data from this institution suggests that the
children with grade 4 stenosis treated with LTR are more likely to require a
subsequent open procedure to achieve decannulation than those treated with CTR.
LTR is a less extensive procedure and is preferred for grade 2, selected grade 3
stenosis. CTR is the preferred option for grade 4 and severe grade 3 stenosis
with a clear margin between the stenosis and the vocal cords.
PMID- 11012645
TI - Sjogren's syndrome.
PMID- 11012646
TI - Powered laryngeal shavers and laryngeal papillomatosis: a preliminary report.
AB - Carbon dioxide (CO2) laser ablation is widely accepted as the most effective
first line surgical treatment of recurrent laryngeal papilloma. However,
vaporization of papilloma with the CO2 laser exposes the patient and staff to a
potentially infective plume. Furthermore, unsuitable pathological tissue
specimens and scarring of the surrounding laryngeal architecture are inevitable
consequences of the thermal energy generated by this instrument. Following their
innovative use in endonasal surgery, powered laryngeal microresecting instruments
(Xomed Shavers) have been developed for laryngeal surgery. We assessed the value
of these new instruments in five patients who had previously undergone laser
ablation. All of the patients reported that their postoperative recovery was the
'same as' or 'better than' that following laser surgery. The surgeon reported
that though there was more bleeding, shaver excision of papilloma provided good
clearance of disease; easy collection of pathological samples; and a potentially
safer and faster alternative to laser excision.
PMID- 11012647
TI - The distribution of hypopnoeic events in relation to apnoeic events in patients
with sleep-induced upper airway narrowing.
AB - The purpose of this study was to investigate patients with sleep-induced upper
airay narrowing to see if: (1) apnoeic and hypopnoeic events regularly coexist;
(2) if sleep-induced upper airway narrowing usually involves more than one level;
and (3) whether the distribution of hypopnoeic events reflects that of apnoeic
events. A retrospective review of 50 patients with sleep-induced upper airway
narrowing was conducted. Recordings were made with a solid-state microtransducer
pressure-catheter and an external thermistor for assessment of the distribution
and number of obstructive events. Ninety-four per cent of the patients had a
mixture of apnoeic and hypopnoeic events. Both transpalatal and subpalatal
obstructions were identified in 84% of patients. In 80% of the patients the level
of apnoeic events, classified as either mainly (> 50% of total) transpalatal
(upper) or subpalatal (lower) reflected that of hypopnoeic events. The percentage
upper to total amount of hypopnoeic events correlated significantly with that of
apnoeic events (R = 0.77, P < 0.001; Spearman rank correlation).
PMID- 11012648
TI - Recurrence and malignant degeneration of 89 cases of inverted papilloma diagnosed
in a non-tertiary referral population between 1975 and 1995: clinical predictors
and p53 studies.
AB - Eighty-nine patients with sinonasal inverted papilloma presenting between 1975
and 1995 were reviewed with the aims of studying predictors of tumour behaviour
and correlating outcome with p53 expression. Correlation of clinical,
radiological features and p53 status was made using chi2 and multiple logistic
regression analysis with recurrence and malignant degeneration as the main
outcome measures. Two patients had synchronous malignancy but no malignant
degeneration was seen. There was no significant difference in recurrence between
minor intranasal procedures and more extensive surgery for the first event.
Younger patients were more likely to recur. (P = 0.0493, odds ratio 0.43). Those
who smoked showed a trend towards multiple recurrence. p53 was expressed in 41%
but did not predict recurrence. Morbidity was related to the extent of surgery.
Inverted papilloma presenting to a non-tertiary centre is more benign than
previously reported. Initial management by less extensive endoscopic surgery may
reduce morbidity.
PMID- 11012649
TI - Head and neck basal cell carcinoma: treatment using a 2-mm clinical excision
margin.
AB - Treatment of basal cell carcinoma (BCC) should completely remove the tumour
whilst preserving the maximum amount of normal surrounding skin. Therefore,
treatment is a compromise between safe excision margins and obtaining a
satisfactory cosmetic result. We report the results of a prospective study of 63
patients who underwent excision of well-demarcated BCCs in the head and neck
region. The surgical excision margin used was 2 mm. Histological assessment
confirmed complete excision in 95% and there was no evidence of recurrence of the
BCC over a 24-month follow-up period in all patients. We propose that a clinical
excision margin of 2 mm is adequate for treatment of simple, well demarcated BCCs
arising in the head and neck.
PMID- 11012650
TI - Management of posterior epistaxis by endoscopic clipping of the sphenopalatine
artery.
AB - Posterior epistaxis poses a challenge to the otolaryngologist as the bleeding
point itself cannot easily be identified. Haemostasis by conventional means is
usually nasal packing and this results in repeated/persistent haemorrhage,
morbidity and prolonged bed occupancy. In recent years the increased availability
of rigid endoscopes and a better understanding of the anatomy of the nasal cavity
have facilitated a direct approach to the sphenopalatine artery. Using a 0
degrees or 30 degrees rigid nasendoscope the sphenopalatine artery-the main blood
supply to the nose-can be clearly identified and treated. Over the last 12 months
we have employed endoscopic intranasal clipping of the said artery under a
general anaesthetic to control persistent posterior nasal bleeding. Twelve
patients have undergone 14 procedures within 48 h of failure of their
conservative management. In all the epistaxis was controlled no complications
were noted. The average follow-up period in our series was nine months. We
believe that intranasal endoscopic clipping of the sphenopalatine artery is
effective and less traumatic than either any other site of arterial ligation
technique or repeated packing. In this series we employed only clipping of the
artery and not diathermy/electrocautery to reduce the theoretical risk to
adjacent structures
PMID- 11012651
TI - Mandibular osteoradionecrosis: clinical behaviour and diagnostic aspects.
AB - We have retrospectively studied 73 patients with mandibular osteoradionecrosis
(ORN) following radiotherapy (high voltage external beam radiation alone, or
combined with brachytherapy) ranging from 50 to 130 Gy (mean 76) with fields
including the mandible. Based on this analysis we defined four distinctive
stages: Stage 0: mucosal defects only; Stage I: radiological evidence of necrotic
bone with intact mucosa; Stage II: positive radiographic findings with denuded
bone intra-orally; Stage III: clinically exposed radionecrotic bone, verified by
imaging techniques, along with skin fistulas and infection. The clinical features
and characteristics of these stages are described, along with their clinical
courses and outcome. The incompleteness of current ORN definitions, mainly
emphasizing mucosal defects and bone exposure, and the need for a revised ORN
classification is pointed out. Based on these observations and the insufficiency
of previous definitions, we arrived at the following ORN definition: Radiological
evidence of bone necrosis within the radiation field, where tumour recurrence has
been excluded.
PMID- 11012652
TI - Brain herniation and chronic otitis media: diagnosis and surgical management.
AB - Herniation of the brain into the middle ear is a rare, but potentially life
threatening complication of chronic otitis media. Fifty patients with a tegmen
defect associated with chronic otitis media were operated on between 1985 and
1998. Among these 50, 15 patients presented brain herniation associated with the
bony defect. Fourteen patients had undergone previous mastoid surgery for chronic
otitis media. Neurological symptoms were encountered in five patients. In 10,
magnetic resonance imaging (MRI) was performed before surgery, and a diagnosis of
brain herniation could be made. The hernia was repaired in all patients using a
middle fossa craniotomy, combined with a transmastoid approach in 11 cases where
a large hernia, and/or inflammatory tissues were present in the mastoid. The
herniated brain tissue was resected in all, and the dural and bony defects were
closed with fascia and bone. No complication or recurrence occurred, during a
mean follow-up of 2 years. In conclusion, the occurrence of severe neurological
complications as a consequence of brain herniation emphasizes the necessity for
recognition and appropriate management of this disease. Computerized tomography
(CT) scanning allows the suspicion of brain herniation, but a definitive
diagnosis can best be established with an MRI study. The hernia should be
repaired using a middle fossa craniotomy, combined with a transmastoid approach
in one or two stages, when necessary.
PMID- 11012653
TI - Age-specific size of the normal adenoid pad on magnetic resonance imaging.
AB - Conclusions regarding the significance and appearance of the adenoids
incidentally noted on magnetic resonance (MR) scans of the brain largely rely on
observations of previously published plain film data. In order to determine the
age specific appearance of normal adenoid tissue as measured on sagittal T1
weighted midline MR images, we evaluated 189 patients without a history or
clinical evidence of adenoid disease, who were sequentially referred for an MR
scan of the brain. The thickness of the adenoid pad was measured to the nearest 1
mm along a line through the pharyngeal tubercle constructed perpendicular to the
anterior clival surface. Patients were grouped according to age. Normal subjects
demonstrated an age specific variation in the size of the pad with the maximal
size being attained in early childhood and then steadily decreasing in later
childhood and adulthood (P = 0.0001). The adenoids were largest in the 7-10 years
age group (mean, 14.59 mm) and steadily declined to 4.83 mm by 60 years of age.
Previous surgery had no effect on adenoid measurement (P = 0.582). Magnetic
resonance scans provide an excellent method for assessing the adenoid pad.
PMID- 11012654
TI - Performance data and survival in head and neck cancer.
AB - A retrospective longitudinal investigation of 2701 patients extending from 1963
was conducted to study the effect of performance status on survival, locoregional
recurrence and associations with host and tumour factors. It was found that those
patients who are physically fit tended to have smaller tumours, less risk of neck
node metastases and more chance of laryngeal cancer. In patients with advanced
disease, locoregional recurrence did not appear to be more common in those with
poor general condition but the death rate from the tumour appeared to increase as
the general physical condition decreased. It is assumed this is due to the
development of distant metastases. There is evidence that immunity is less well
developed in those with poor general condition and this in turn, may be due to
alcohol abuse and poor general nutrition.
PMID- 11012655
TI - Evaluation of the Herbst Mandibular Advancement Splint in the management of
patients with sleep-related breathing disorders.
AB - Sleep-related breathing disorders such as snoring and obstructive sleep apnoea
syndrome are the cause of significant social disruption and hypersomnolence.
Several intraoral appliances for the treatment of these disorders have been
described, especially where nasal continuous positive airway pressure is poorly
tolerated. Mandibular Advancement Splints, such as the Herbst splint used in this
study can also be offered to patients with mild to moderate sleep apnoea and
simple snorers. The success and compliance rate noted in the literature are quite
diverse. Few side-effects have been reported. We therefore undertook this study
to assess: (1) the compliance; (2) the effectiveness; and (3) the side-effects in
the long- and short-term. All patients for whom a Herbst splint had been
prescribed in the last 18 months were sent a postal questionnaire regarding the
above mentioned issues. In all, 179 questionnaires were posted and on analysis of
the 132 returned it was noted that 82% of splints were worn and 88% of patients
found the device to be effective. The long-term side-effects were minimal. In
addition objective assessment on 10 patients with and without a jaw-retaining
device was also obtained. We conclude that the Herbst Mandibular Advancement
Splint is a justifiable option in selected subjects with sleep-related breathing
disorders.
PMID- 11012656
TI - A randomised controlled trial of the effect of regional nerve blocks on immediate
post-tonsillectomy pain in adult patients.
AB - Post-operative pain is the main cause of morbidity following tonsillectomy. The
efficacy of glossopharyngeal and lesser palatine nerve blocks in controlling
postoperative pain in adult patients was investigated prospectively. Patients 16
years and older admitted for elective tonsillectomy were randomised to one of
three groups to receive a pre-incisional oropharyngeal injection of 0.5%
bupivicaine, a 'dummy' injection of saline or no injection. Dissection
tonsillectomy and general anaesthetic techniques were standardized. Postoperative
pain was monitored for 24 h. ANOVA, chi2 and Fisher's exact test were used for
intergroup comparisons. Ninety-two patients (72 women and 20 men), mean age 22
years were studied. Twenty-nine patients received 0.5% bupivicaine, 30 saline and
33 no pre-incisional injection. The overall mean pain scores of 2.1, 1.9 and 1.9
in the bupivicaine, saline and no injection groups were similar. Glossopharyngeal
and lesser palatine 0.5% bupivicaine nerve blocks are not effective in reducing
early post-tonsillectomy pain.
PMID- 11012657
TI - The effect of Isshiki type 1 thyroplasty on quality of life and vocal
performance.
AB - Type 1 thyroplasty for unilateral vocal cord palsy improves many vocal outcome
measures but there is little information on quality of life despite its
increasingly recognized importance. Our prospective study examined its effect on
a range of subjective and objective measures and quality of life. Twenty-seven
patients underwent thyroplasty. Before and after surgery they completed a vocal
performance questionnaire and the Nottingham Health Profile (NHP); instrumental
analyses of jitter, shimmer and noise-harmonic ratio (NHR); and perceptual
analyses of grade, roughness, breathiness, aesthenia and strain (GRBAS) were also
performed. Significant improvements were found in instrumental, perceptual and
self-assessment of voice and the energy, social and emotional dimensions of the
NHP. Three patients had initially poor results but were successfully revised.
These results of type 1 thyroplasty compare favourably with those previously
published. The improvement in quality of life appears to result directly from
improved voice. Many thyroplasty patients have limited life expectancy: early
surgical intervention should be considered.
PMID- 11012658
TI - Acoustic rhinometric evaluation of the nasal response to exercise in patients
with nasal septal deviation.
AB - We aimed to investigate nasal response to exercise in patients with a nasal
septal deviation. Acoustic rhinometric measurements of cross-sectional areas
(CSA) at 3.3, 4.0, 6.4 cm from the nostril, and nasal volume (NV) were conducted
in 10 patients. The consecutive measurements were undertaken just before and
immediately after 10, 20, and 30 min of treadmill exercise. In the concave nasal
cavities, NV and CSA at 3.3 cm and 6.4 cm from the nostril showed a significant
increase in immediate post-exercise and 10-minute post-exercise measurements. At
4.0 cm from the nostril, a significant increase was sustained by 20 min after
exercise. However, in convex nasal cavities, exercise did not result in a
significant increase except for the immediate post-exercise measurement at 4 cm
from the nostril. The results of this study indicated that, in nasal septal
deviation, the mucosal response is more prominent in the concave nasal cavities
than in the convex nasal cavities.
PMID- 11012659
TI - Spontaneous resolution of tonsillitis in children on the waiting list for
tonsillectomy.
AB - The aim of this study was to determine whether children undergo spontaneous
resolution of recurrent acute tonsillitis whilst awaiting surgery. Eighty
children who had been on the waiting list for tonsillectomy for at least 9 months
were requested to attend a review clinic with a second review 6 months later if
appropriate. Nineteen (27%) of the 70 children who completed the study no longer
warranted surgery and were removed from the waiting list. We conclude that those
children who have been on the waiting list for a long period of time should be
reassessed prior to the planned tonsillectomy to see if surgery is still
indicated.
PMID- 11012660
TI - Thioredoxin-thioredoxin reductase--a system that has come of age.
PMID- 11012661
TI - Physiological functions of thioredoxin and thioredoxin reductase.
AB - Thioredoxin, thioredoxin reductase and NADPH, the thioredoxin system, is
ubiquitous from Archea to man. Thioredoxins, with a dithiol/disulfide active site
(CGPC) are the major cellular protein disulfide reductases; they therefore also
serve as electron donors for enzymes such as ribonucleotide reductases,
thioredoxin peroxidases (peroxiredoxins) and methionine sulfoxide reductases.
Glutaredoxins catalyze glutathione-disulfide oxidoreductions overlapping the
functions of thioredoxins and using electrons from NADPH via glutathione
reductase. Thioredoxin isoforms are present in most organisms and mitochondria
have a separate thioredoxin system. Plants have chloroplast thioredoxins, which
via ferredoxin-thioredoxin reductase regulates photosynthetic enzymes by light.
Thioredoxins are critical for redox regulation of protein function and signaling
via thiol redox control. A growing number of transcription factors including NF
kappaB or the Ref-1-dependent AP1 require thioredoxin reduction for DNA binding.
The cytosolic mammalian thioredoxin, lack of which is embryonically lethal, has
numerous functions in defense against oxidative stress, control of growth and
apoptosis, but is also secreted and has co-cytokine and chemokine activities.
Thioredoxin reductase is a specific dimeric 70-kDa flavoprotein in bacteria,
fungi and plants with a redox active site disulfide/dithiol. In contrast,
thioredoxin reductases of higher eukaryotes are larger (112-130 kDa), selenium
dependent dimeric flavoproteins with a broad substrate specificity that also
reduce nondisulfide substrates such as hydroperoxides, vitamin C or selenite. All
mammalian thioredoxin reductase isozymes are homologous to glutathione reductase
and contain a conserved C-terminal elongation with a cysteine-selenocysteine
sequence forming a redox-active selenenylsulfide/selenolthiol active site and are
inhibited by goldthioglucose (aurothioglucose) and other clinically used drugs.
PMID- 11012662
TI - Thioredoxin reductase two modes of catalysis have evolved.
AB - Thioredoxin reductase (EC 1.6.4.5) is a widely distributed flavoprotein that
catalyzes the NADPH-dependent reduction of thioredoxin. Thioredoxin plays several
key roles in maintaining the redox environment of the cell. Like all members of
the enzyme family that includes lipoamide dehydrogenase, glutathione reductase
and mercuric reductase, thioredoxin reductase contains a redox active disulfide
adjacent to the flavin ring. Evolution has produced two forms of thioredoxin
reductase, a protein in prokaryotes, archaea and lower eukaryotes having a Mr of
35 000, and a protein in higher eukaryotes having a Mr of 55 000. Reducing
equivalents are transferred from the apolar flavin binding site to the protein
substrate by distinct mechanisms in the two forms of thioredoxin reductase. In
the low Mr enzyme, interconversion between two conformations occurs twice in each
catalytic cycle. After reduction of the disulfide by the flavin, the pyridine
nucleotide domain must rotate with respect to the flavin domain in order to
expose the nascent dithiol for reaction with thioredoxin; this motion repositions
the pyridine ring adjacent to the flavin ring. In the high Mr enzyme, a third
redox active group shuttles the reducing equivalent from the apolar active site
to the protein surface. This group is a second redox active disulfide in
thioredoxin reductase from Plasmodium falciparum and a selenenylsulfide in the
mammalian enzyme. P. falciparum is the major causative agent of malaria and it is
hoped that the chemical difference between the two high Mr forms may be exploited
for drug design.
PMID- 11012663
TI - Thioredoxin reductase as a pathophysiological factor and drug target.
AB - Human cytosolic thioredoxin reductase (TrxR), a homodimeric protein containing 1
selenocysteine and 1 FAD per subunit of 55 kDa, catalyses the NADPH-dependent
reduction of thioredoxin disulfide and of numerous other oxidized cell
constituents. As a general reducing enzyme with little substrate specificity, it
also contributes to redox homeostasis and is involved in prevention, intervention
and repair of damage caused by H2O2-based oxidative stress. Being a selenite
reducing enzyme as well as a selenol-containing enzyme, human TrxR plays a
central role in selenium (patho)physiology. Both dietary selenium deficiency and
selenium oversupplementation, a lifestyle phenomenon of our time, appear to
interfere with the activity of TrxR. Selenocysteine 496 of human TrxR is a major
target of the anti-rheumatic gold-containing drug auranofin, the formal Ki for
the stoichiometric inhibition being 4 nM. The hypothesis that TrxR and
extracellular thioredoxin play a pathophysiologic role in chronic diseases such
as rheumatoid arthritis, Sjogren's syndrom, AIDS, and certain malignancies, is
substantiated by biochemical, virological, and clinical evidence. Reduced
thioredoxin acts as an autocrine growth factor in various tumour diseases, as a
chemoattractant, and it synergises with interleukins 1 and 2. The effects of anti
tumour drugs such as carmustine and cisplatin can be explained in part by the
inhibition of TrxR. Consistently, high levels of the enzyme can support drug
resistance. TrxRs from different organisms such as Escherichia coli,
Mycobacterium leprae, Plasmodium falciparum, Drosophila melanogaster, and man
show a surprising diversity in their chemical mechanism of thioredoxin reduction.
This is the basis for attempts to develop specific TrxR inhibitors as drugs
against bacterial infections like leprosy and parasitic diseases like amebiasis
and malaria.
PMID- 11012664
TI - AhpF and other NADH:peroxiredoxin oxidoreductases, homologues of low Mr
thioredoxin reductase.
AB - A group of bacterial flavoproteins related to thioredoxin reductase contain an
additional approximately 200-amino-acid domain including a redox-active disulfide
center at their N-termini. These flavoproteins, designated NADH:peroxiredoxin
oxidoreductases, catalyze the pyridine-nucleotide-dependent reduction of cysteine
based peroxidases (e.g. Salmonella typhimurium AhpC, a member of the
peroxiredoxin family) which in turn reduce H2O2 or organic hydroperoxides. These
enzymes catalyze rapid electron transfer (kcat > 165 s-1) through one tightly
bound FAD and two redox-active disulfide centers, with the N-terminal-most
disulfide center acting as a redox mediator between the thioredoxin-reductase
like part of these proteins and the peroxiredoxin substrates. A chimeric protein
with the first 207 amino acids of S. typhimurium AhpF attached to the N-terminus
of Escherichia coli thioredoxin reductase exhibits very high NADPH:peroxiredoxin
oxidoreductase and thioredoxin reductase activities. Catalytic turnover by
NADH:peroxiredoxin oxidoreductases may involve major domain rotations, analogous
to those proposed for bacterial thioredoxin reductase, and cycling of these
enzymes between two electron-reduced (EH2) and four electron-reduced (EH4) redox
states.
PMID- 11012665
TI - Catalytic differences between porcine blastocyst and placental aromatase
isozymes.
AB - Two isozymes of porcine aromatase, the placental and the blastocyst forms, were
expressed in CHO cells using the mammalian cell transfection method. Using an 'in
cell' assay (a 3H-water release method), catalytic parameters of the porcine
placental aromatase were found to be very similar to those of the human enzyme;
however, the activity of the blastocyst isozyme was found to be one-thirtieth
that of the placental isozyme. Product isolation assay (using testosterone as the
substrate) revealed that the major steroid products were 17beta-estradiol and 19
nortestosterone. The product ratio of estradiol/19-nortestosterone was found to
be 94 : 6 for the porcine placental form, 6 : 94 for the porcine blastocyst form,
and 92 : 8 for the human wild-type aromatase. Therefore, the porcine blastocyst
aromatase isozyme catalyzes mainly androgen 19-desmethylation rather than
aromatization. In addition, inhibition profile analyses on the placental and
blastocyst isozymes were performed using three steroidal inhibitors [4
hydroxyandro-stenedione (4-OHA), 7alpha-(4'-amino)phenylthio-1, 4-androstandiene
3,17-dione (7alpha-APTADD), and bridge (2, 19-methyleneoxy) androstene-3,17-dione
(MDL 101,003)], and four nonsteroidal inhibitors [aminoglutethimide (AG), CGS
20267, ICI D1033, and vorozole (R83842)]. While the two isozymes of porcine
aromatase share 93% amino-acid sequence identity, our results indicate that the
two porcine aromatase isozymes have distinct responses to various aromatase
inhibitors.
PMID- 11012666
TI - Cloning, expression and chromosomal localization of a novel human dipeptidyl
peptidase (DPP) IV homolog, DPP8.
AB - Dipeptidyl peptidase (DPP) IV has roles in T-cell costimulation, chemokine
biology, type-II diabetes and tumor biology. Fibroblast activation protein (FAP)
has been implicated in tumor growth and cirrhosis. Here we describe DPP8, a novel
human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP.
Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is
ubiquitous, similar to that of DPPIV. The DPP8 gene was localized to chromosome
15q22, distinct from a closely related gene at 19p13.3 which we named DPP9. The
full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27%
identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no
N-linked or O-linked glycosylation. Western blots and confocal microscopy of
transfected COS-7 cells showed DPP8 to be a 100-kDa monomeric protein expressed
in the cytoplasm. Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala
Pro, Arg-Pro and Gly-Pro. Thus recombinant DPP8 shares a postproline dipeptidyl
aminopeptidase activity with DPPIV and FAP. DPP8 enzyme activity had a neutral pH
optimum consistent with it being nonlysosomal. The similarities between DPP8 and
DPPIV in tissue expression pattern and substrates suggests a potential role for
DPP8 in T-cell activation and immune function.
PMID- 11012667
TI - Functional regions in the essential light chain of smooth muscle myosin as
revealed by the mutagenesis approach.
AB - The endogenous essential light chain (LC17) of myosin from intestine smooth
muscle was replaced with mutated essential light chains prepared using
recombinant techniques. Complete exchange was observed with histidine-tagged
derivatives of LC17a, LC17b and E122A-LC17a (LC17a and LC17b are the usual
constituants of smooth muscle myosin), with small changes in the ATPase activity
of reconstituted myosins. Much less exchange was observed with the light-chain
derivative lacking the last 12 amino acid residues, demonstrating the importance
of this segment, which may act as one arm of a pair of pincers to bind the myosin
heavy chain.
PMID- 11012668
TI - Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24.
AB - Human 25-hydroxyvitamin D3 (25(OH)D3) 24-hydroxylase (CYP24) cDNA was expressed
in Escherichia coli, and its enzymatic and spectral properties were revealed. The
reconstituted system containing the membrane fraction prepared from recombinant
E. coli cells, adrenodoxin and adrenodoxin reductase was examined for the
metabolism of 25(OH)D3, 1alpha,25(OH)2D3 and their related compounds. Human CYP24
demonstrated a remarkable metabolism consisting of both C-23 and C-24
hydroxylation pathways towards both 25(OH)D3 and 1alpha,25(OH)2D3, whereas rat
CYP24 showed almost no C-23 hydroxylation pathway [Sakaki, T. Sawada, N. Nonaka,
Y. Ohyama, Y. & Inouye, K. (1999) Eur. J. Biochem. 262, 43-48]. HPLC analysis and
mass spectrometric analysis revealed that human CYP24 catalyzed all the steps of
the C-23 hydroxylation pathway from 25(OH)D3 via 23S, 25(OH)2D3, 23S,25,26(OH)3D3
and 25(OH)D3-26,23-lactol to 25(OH)D3-26, 23-lactone in addition to the C-24
hydroxylation pathway from 25(OH)D3 via 24R,25(OH)2D3, 24-oxo-25(OH)D3, 24-oxo
23S,25(OH)2D3 to 24,25,26,27-tetranor-23(OH)D3. On 1alpha,25(OH)2D3 metabolism,
similar results were observed. These results strongly suggest that the single
enzyme human CYP24 is greatly responsible for the metabolism of both 25(OH)D3 and
1alpha,25(OH)2D3. We also succeeded in the coexpression of CYP24, adrenodoxin and
NADPH-adrenodoxin reductase in E. coli. Addition of 25(OH)D3 to the recombinant
E. coli cell culture yielded most of the metabolites in both the C-23 and C-24
hydroxylation pathways. Thus, the E. coli expression system for human CYP24
appears quite useful in predicting the metabolism of vitamin D analogs used as
drugs.
PMID- 11012669
TI - Dual nature of the distal histidine residue in the autoxidation reaction of
myoglobin and hemoglobin comparison of the H64 mutants.
AB - The oxygenated form of myoglobin or hemoglobin is oxidized easily to the ferric
met-form with generation of the superoxide anion. To make clear the possible
role(s) of the distal histidine (H64) residue in the reaction, we have carried
out detailed pH-dependence studies of the autoxidation rate, using some typical
H64 mutants of sperm whale myoglobin, over the wide range of pH 5-12 in 0.1 M
buffer at 25 degrees C. Each mutation caused a dramatic increase in the
autoxidation rate with the trend H64V >/= H64G >/= H64L >> H64Q > H64 (wild-type)
at pH 7.0, whereas each mutant protein showed a characteristic pH-profile which
is essentially different from that of the wild-type or native sperm whale MbO2.
In particular, all the mutants have lost the acid-catalyzed process that can play
a dominant role in the autoxidation reaction of most mammalian myoglobins or
hemoglobins. Kinetic analyses of various types of pH-profiles lead us to conclude
that the distal histidine residue can play a dual role in the nucleophilic
displacement of O2- from MbO2 or HbO2 in protic, aqueous solution. One is in a
proton-relay mechanism via its imidazole ring, and the other is in the maximum
protection of the FeO2 center against a water molecule or an hydroxyl ion that
can enter the heme pocket from the surrounding solvent.
PMID- 11012670
TI - Purification and primary structure of a new bovine spermadhesin.
AB - Z13 is a new seminal plasma protein made up of two disulfide-linked 13-kDa
subunits that was identified in our laboratory by 2D PAGE. In this report we
present the purification of Z13 from bovine seminal plasma. In solution, the
protein is a nonglycosylated dimer that presents one interchain disulfide bond
and does not show heparin-binding properties. The complete primary structure and
the localization of the S-S bridges are reported. The results suggest that Z13 is
a new protein of the spermadhesin family whose members are thought to play a
prominent role in different aspects of fertilization.
PMID- 11012671
TI - Regulation of Gadd45gamma expression by C/EBP.
AB - The Gadd45gamma (growth arrest and DNA damage-inducible) gene is activated
transcriptionally by at least two kinds of agents: DNA damaging agent such as
methyl methanesulfonate (MMS) and UV radiation, or cytokines such as interleukin
(IL)-6, IL-2 and granulocyte colony-stimulating factor (G-CSF). To investigate
the sequences and transcription factors involved in induction of Gadd45gamma
after treatment with IL-6, the human gene was cloned and sequenced. We found
C/EBP (CCAAT/enhancer-binding protein) family proteins, major transcription
factors in the IL-6 signal transduction pathway, could regulate the
transcriptional activity of the Gadd45gamma promoter. In addition, a noncanonical
C/EBP-binding site within the Gadd45gamma promoter where C/EBPbeta and C/EBPdelta
could bind, was identified by electrophoretic mobility shift assay (EMSA) and
reporter gene analysis. Furthermore, we found a coordinated expression profile
between Gadd45gamma mRNA and C/EBPs (beta and delta) protein during the
differentiation of M1 cells: the amount of Gadd45gamma transcripts became maximal
when both C/EBPbeta and C/EBPdelta levels were high, on day 1 of differentiation
of M1 cells after treatment with IL-6. These findings suggest that mitotic growth
arrest coupled to M1 cell differentiation is mediated by C/EBPs stimulation of
growth arrest-associated genes such as Gadd45gamma.
PMID- 11012672
TI - A masquerade-like serine proteinase homologue is necessary for phenoloxidase
activity in the coleopteran insect, Holotrichia diomphalia larvae.
AB - Previously, we reported the molecular cloning of cDNA for the prophenoloxidase
activating factor-I (PPAF-I) that encoded a member of the serine proteinase group
with a disulfide-knotted motif at the N-terminus and a trypsin-like catalytic
domain at the C-terminus [Lee, S.Y., Cho, M.Y., Hyun, J.H., Lee, K.M., Homma,
K.I., Natori, S. , Kawabata, S.I., Iwanaga, S. & Lee, B.L. (1998) Eur. J.
Biochem. 257, 615-621]. PPAF-I is directly involved in the activation of pro
phenoloxidase (pro-PO) by limited proteolysis and the overall structure is highly
similar to that of Drosophila easter serine protease, an essential serine
protease zymogen for pattern formation in normal embryonic development. Here, we
report purification and molecular cloning of cDNA for another 45-kDa novel PPAF
from the hemocyte lysate of Holotrichia diomphalia larvae. The gene encodes a
serine proteinase homologue consisting of 415 amino-acid residues with a
molecular mass of 45 256 Da. The overall structure of the 45-kDa protein is
similar to that of masquerade, a serine proteinase homologue expressed during
embryogenesis, larval, and pupal development in Drosophila melanogaster. The 45
kDa protein contained a trypsin-like serine proteinase domain at the C-terminus,
except for the substitution of Ser of the active site triad to Gly and had a
disulfide-knotted domain at the N-terminus. A highly similar 45-kDa serine
proteinase homologue was also cloned from the larval cDNA library of another
coleopteran, Tenebrio molitor. By in vitro reconstitution experiments, we found
that the purified 45-kDa serine proteinase homologue, the purified active PPAF-I
and the purified pro-PO were necessary for expressing phenoloxidase activity in
the Holotrichia pro-PO system. However, incubation of pro-PO with either PPAF-I
or 45-kDa protein, no phenoloxidase activity was observed. Interestingly, when
the 45-kDa protein was incubated with PPAF-I and pro-PO in the absence, but not
in the presence of Ca2+, the 45-kDa protein was cleaved to a 35-kDa protein. RNA
blot hybridization revealed that expression of the 45-kDa protein was increased
in the Holotrichia hemolymph after Escherichia coli challenge.
PMID- 11012673
TI - Shifting the NAD/NADP preference in class 3 aldehyde dehydrogenase.
AB - Among pyridine-nucleotide-dependent oxidoreductases, the class 3 family of
aldehyde dehydrogenases (ALDHs) is unusual in its ability to function with either
NAD or NADP. This is all the more surprising because an acidic residue, Glu140,
coordinates the adenine ribose 2' hydroxyl. In many NAD-dependent dehydrogenases
a similarly placed carboxylate is thought to be responsible for exclusion of
NADP. The corresponding residue in most (approximately 71%) sequences in the ALDH
extended family is also Glu, and most of these are NAD-specific enzymes. Site
directed mutagenesis was performed on this residue in rat class 3 ALDH. Our
results indicate that this residue contributes to tighter binding of NAD in the
native enzyme, but suggest that additional factors must contribute to the ability
to utilize NADP. Mutagenesis of an adjacent basic residue (Lys137) indicates that
it is even more essential for binding both coenzymes, consistent with its
conservation in nearly all ALDHs (> 98%).
PMID- 11012674
TI - Spectroscopic probing of the influence of calcium and the gla domain on the
interaction between the first EGF domain in factor VIIa and tissue factor.
AB - The binding of factor VIIa (FVIIa) to tissue factor (TF) initiates blood
coagulation. The binary complex is dependent on Ca2+ binding to several sites in
FVIIa and is maintained by multiple contacts distributed throughout the various
domains. Although the contributions from various residues and domains, including
the Ca2+ coordination, to the global binding energy have been characterized,
their importance for specific local interactions is virtually unknown. To address
this aspect, we have attached four spectroscopic probes to an engineered Cys
residue replacing Phe140 in soluble TF (sTF). This allows the monitoring of local
changes in hydrophobicity and rigidity upon complex formation at the interface
between the first epidermal growth factor-like (EGF1) domain of FVIIa and sTF.
The fluorescent labels used sense a more hydrophobic environment and the spin
labels are dramatically immobilized when FVIIa binds sTF. The results obtained
with a 4-carboxyglutamic acid (Gla)-domainless derivative of FVIIa indicate that
the Gla domain has no or minimal influence on the interaction between EGF1 and
sTF. However, there is a difference in local Ca2+ dependence between Gla
domainless and full-length FVIIa.
PMID- 11012675
TI - Identification of novel prostate-specific antigen-binding peptides modulating its
enzyme activity.
AB - Prostate-specific antigen (PSA) is a serine protease with highly prostate
specific expression. Measurement of PSA in serum is widely used for diagnosis and
monitoring of prostate cancer. PSA dissolves the seminal gel forming after
ejaculation. It has been suggested to mediate invasion and metastasis of prostate
cancer but also to exert antiangiogenic activity. We have identified peptides
specific for PSA by screening cyclic phage display peptide libraries. PSA-binding
peptides were isolated from four different libraries and produced as a fusion
protein with glutathione S-transferase (GST). The phage and fusion proteins were
shown to bind to PSA specifically as indicated by lack of binding to other serine
proteinases. A peptide with four cysteines showed the highest affinity for PSA.
Zn2+, an inhibitor of PSA activity, increased the affinity of the peptides to
PSA. The binding specificity was characterized by cross-inhibition using
monoclonal anti-PSA antibodies of known epitope specificities. The peptides bound
to the same region as mAbs specific for free PSA indicating that they bind close
to the active site of the enzyme. The peptides enhanced the enzyme activity of
PSA against a chromogenic substrate. These results show that peptides binding to
PSA and modulating its enzyme activity can be developed by phage display
technique. The peptides have the potential to be used for identification of PSA
variants and for imaging and targeting of prostatic tumors.
PMID- 11012676
TI - Kinetic evidences for facilitation of peptide channelling by the proteasome
activator PA28.
AB - The activation kinetics of constitutive and IFNgamma-stimulated 20S proteasomes
obtained with homomeric (recPA28alpha, recPA28beta) and heteromeric
(recPA28alphabeta) forms of recombinant 11S regulator PA28 was analysed by means
of kinetic modelling. The activation curves obtained with increasing
concentrations of the individual PA28 subunits
(RecP28alpha/RecP28beta/RecP28alpha + RecP28beta) exhibit biphasic
characteristics which can be attributed to a low-level activation by PA28
monomers and full proteasome activation by assembled activator complexes. The
dissociation constants do not reveal significant differences between the
constitutive and the immunoproteasome. Intriguingly, the affinity of the
proteasome towards the recPA28alphabeta complex is about two orders of magnitude
higher than towards the homomeric PA28alpha and PA28beta complexes. Striking
similarities can been revealed in the way how PA28 mediates the kinetics of
latent proteasomes with respect to three different fluorogenic peptides probing
the chymotrypsin-like, trypsin-like and peptidylglutamyl-peptide hydrolyzing like
activity: (a) positive cooperativity disappears as indicated by a lack of sigmoid
initial parts of the kinetic curves, (b) substrate affinity is increased, whereby
(c), the maximal activity remains virtually constant. As these kinetic features
are independent of the peptide substrates, we conclude that PA28 exerts its
activating influence on the proteasome by enhancing the uptake (and release) of
shorter peptides.
PMID- 11012677
TI - The assembly factor P17 from bacteriophage PRD1 interacts with positively charged
lipid membranes.
AB - The interactions of the assembly factor P17 of bacteriophage PRD1 with liposomes
were investigated by static light scattering, fluorescence spectroscopy, and
differential scanning calorimetry. Our data show that P17 binds to positively
charged large unilamellar vesicles composed of the zwitterionic 1-palmitoyl-2
oleoyl-phosphatidylcholine and sphingosine, whereas only a weak interaction is
evident for 1-palmitoyl-2-oleoyl-phosphatidylcholine vesicles. P17 does not bind
to negatively charged membranes composed of 1-palmitoyl-2-oleoyl
phosphatidylglycerol and 1-palmitoyl-2-oleoyl-phosphatidylcholine. Our
differential scanning calorimetry results reveal that P17 slightly perturbs the
phase behaviour of neutral phosphatidylcholine and negatively charged
multilamellar vesicles. In contrast, the phase transition temperature of
positively charged dimyristoylphosphatidylcholine/sphingosine multilamellar
vesicles (molar ratio 9 : 1, respectively) is increased by approximately 2.4
degrees C and the half width of the enthalpy peak broadened from 1.9 to 5.6
degrees C in the presence of P17 (protein : lipid molar ratio 1 : 47). Moreover,
the enthalpy peak is asymmetrical, suggesting that lipid phase separation is
induced by P17. Based on the far-UV CD spectra, the alpha-helicity of P17
increases upon binding to positively charged micelles composed of Triton X-100
and sphingosine. We propose that P17 can interact with positively charged lipid
membranes and that this binding induces a structural change on P17 to a more
tightly packed and ordered structure.
PMID- 11012678
TI - Interaction of the targeting sequence of chloroplast precursors with Hsp70
molecular chaperones.
AB - We have analyzed the interaction of DnaK and plant Hsp70 proteins with the wild
type ferredoxin-NADP+ reductase precursor (preFNR) and mutants containing amino
acid replacements in the targeting sequence. Using an algorithm already developed
[Rudiger, S., Germeroth, L., Schneider-Mergener, J. & Bukau, B. (1997) EMBO J.
16, 1501-1507] we observed that 75% of the 727 plastid precursor proteins
analyzed contained at least one site with high likelihood of DnaK binding in
their transit peptides. Statistical analysis showed a decrease of DnaK binding
site frequency within the first 15 amino-acid residues of the transit peptides.
Using fusion proteins we detected the interaction of DnaK with the transit
peptide of the folded preFNR but not with the mature region of the protein.
Discharge of DnaK from the presequence was favored by addition of MgATP. When a
putative DnaK binding site was artificially added at the N-terminus of the mature
protein, we observed formation of complexes with bacterial and plant Hsp70
molecular chaperones. Reducing the likelihood of DnaK binding by directed
mutagenesis of the presequence increased the release of bound DnaK. The Hsp70
proteins from plastids and plant cell cytosol also interacted with the preFNR
transit peptide. Overall results are discussed in the context of the proposed
models to explain the organelle protein import.
PMID- 11012679
TI - The rat kidney acylase I, characterization and molecular cloning. Differences
with other acylases I.
AB - The soluble acylase I from rat kidney was purified to homogeneity using a five
step procedure. As the resulting protein was found to have a relative molecular
mass of 125 kDa based on size-exclusion chromatography and 44 kDa based on
SDS/PAGE, the native protein was taken to consist of three subunits. The amino
acid sequence of a peptide resulting from limited proteolysis of the polypeptide
chain with proteinase K, which was determined by microsequencing
(RHEFHALRAGFALDEGLA), was found to be very similar to the corresponding sequence
of porcine kidney acylase I. However, as N-furyl-acryloyl-L-methionine, a
synthetic substrate for porcine acylases, was not hydrolyzed by the rat enzyme,
it was suggested that the polypeptide chain might differ in other respects from
those of the other acylases I. A full length cDNA coding for the rat kidney
acylase I was therefore isolated and found to contain a 1224-bp open reading
frame encoding a protein consisting of 408 amino-acid residues, which
corresponded to a calculated molecular mass of 45 847 Da per subunit. The deduced
amino-acid sequence showed 93.6% and 87.2% identity with that of the human liver
and porcine kidney, respectively.
PMID- 11012680
TI - Signal transduction pathways triggered by fibroblast growth factor receptor 1
expressed in Xenopus laevis oocytes after fibroblast growth factor 1 addition.
Role of Grb2, phosphatidylinositol 3-kinase, Src tyrosine kinase, and
phospholipase Cgamma.
AB - Xenopus oocytes expressing fibroblast growth factor receptor 1 (FGFR1) were used
as a biological model system to analyse the signal transduction pathways that are
triggered by fibroblast growth factor 1 (FGF1). Germinal vesicle breakdown (GVBD)
and phosphorylation of extracellular signal-regulated protein kinase 2 (ERK2)
occured 15 h after FGF1 addition. These events were Ras-dependent as they were
blocked by a Ras dominant negative form. The Ras activity was promoted by three
upstream effectors, growth factor-bound protein 2 (Grb2), phosphatidylinositol 3
kinase (PI3K) and Src cytoplasmic kinase. Ras activation was inhibited by a Grb2
dominant negative form (P49L), by PI3K inhibitors, including wortmannin,
LY294002, the N-SH2 domain of p85alpha PI3K and by the SH2 domain of Src. Src
activation induced by FGF1 was blocked by the SH2 domain of Src and PP2, a
specific inhibitor of Src. The Grb2 adaptor was recruited by the upstream Src
homology 2/alpha-collagen-related (Shc) effector, as the SH2-Shc domain prevented
the GVBD and the ERK2 phosphorylation induced by FGF1. The importance of another
signalling pathway involving phospholipase Cgamma (PLCgamma) was also
investigated. The use of the PLCgamma inhibitory peptide, neomycin and the
calcium chelator BAPTA-AM on oocytes expressing FGFR1 or the stimulation by PDGF
BB of oocytes expressing PDGFR-FGFR1 mutated on the PLCgamma binding site,
prevented GVBD and ERK2 phosphorylation. This study shows that the transduction
cascade induced by the FGFR1-FGF1 interaction in Xenopus oocytes represents the
sum of Ras-dependent and PLCgamma-dependent pathways. It emphasizes the role
played by PI3K and Src and their connections with the Ras cascade in the FGFR1
signal transduction.
PMID- 11012681
TI - Interaction of peroxisomes with microtubules. In vitro studies using a novel
peroxisome-microtubule binding assay.
AB - The association of membrane-bounded cell organelles to microtubules is crucial
for determination of their shape, intracellular localization and translocation.
We have shown previously the high affinity binding of peroxisomes to microtubules
which appears to be of static nature as in vivo studies indicate that only a few
peroxisomes move along the microtubular tracks. In order to characterize the
interactions of peroxisomes with microtubules, we have developed a
semiquantitative in vitro binding assay, which is based on the association of
highly purified rat liver peroxisomes to microtubules coated onto
microtiterplates. The binding was visualized by differential interference
contrast and immunofluorescence using a confocal laser scanning microscope. The
binding was concentration dependent and saturable, being affected by time,
temperature, and pH. Addition of ATP or the motor proteins kinesin and dynein
increased the binding capacity, while ATP-depletion or microtubule associated
proteins (MAPs) decreased it. KCl treatment of peroxisomes reduced the binding,
which was restored by dialyzed KCl-stripping eluate as well as by rat liver
cytosol. The reconstituting effect of cytosol was abolished by its pretreatment
with proteases or N-ethylmaleimide. Moreover, the treatment of peroxisomes with
proteases or N-ethylmaleimide reduced their binding, which was not reversed by
cytosol. These results suggest the involvement of a peroxisomal membrane protein
and cytosolic factor(s) in the binding of peroxisomes to microtubules. This
notion is supported by the observation that distinct subfractions of dialyzed KCl
stripping eluate obtained by gel chromatography augmented the binding. Those
subfractions, as well as purified peroxisome fractions, exhibited strong
immunoreactivity with an antibody to cytoplasmic linker protein (CLIP)-115,
revealing a 70-kDa polypeptide. Moreover, immunodepletion of KCl-stripping eluate
and its subfractions with an antibody to the conserved microtubule binding domain
of CLIPs, abolished their promoting effect on the binding, thus suggesting the
involvement of a CLIP-related protein in the binding of peroxisomes to
microtubules.
PMID- 11012682
TI - Ether lipids in the cell membrane of Mycoplasma fermentans.
AB - Two new ether lipids, 1-O-alkyl/alkenyl-2-O-acyl-glycero-3-phosphocholine and its
lyso form, 1-O-alkyl/alkenyl-glycero-3-phosphocholine, were identified in the
cell membrane of Mycoplasma fermentans using chemical analyses, GLC-MS, MALDI-TOF
MS, and 1D and 2D NMR spectroscopy. The lipids are heterogeneous with respect to
both acyl and alkyl/alkenyl residues. The acyl residues at position 2 of glycerol
are hexadecanoyl and octadecanoyl in a molar ratio of 3.6 : 1 with a trace amount
of octadecenoyl. The alkyl/alkenyl residues at position 1 of glycerol are
hexadecyl (78%), octadecyl (7%), octadecenyl (14%), and hexadecenyl (traces). In
the octadecenyl residue, the double bond has a cis configuration and is located
at either position 1' (plasmalogen-type lipid) or 9' in a ratio approximately 1 :
1. This is the first report of the presence of alkyl and vinyl (alk-1'-enyl)
ether lipids in the cell membrane of aerobically grown mycoplasmas. Lipids of
this type have been found in some Gram-positive bacteria, thus supporting the
hypothesized close taxonomical relationship of these bacteria to mycoplasmas. The
ether lipids of M. fermentans are structurally similar to platelet activating
factor; it was demonstrated that the 2-O-acetylated lyso form lipid can mimic
platelet-activating factor activity in isolated perfused and ventilated rat
lungs.
PMID- 11012683
TI - Comparison of the substrate specificity of the human T-cell leukemia virus and
human immunodeficiency virus proteinases.
AB - Human T-cell leukemia virus type-1 (HTLV-1) is associated with a number of human
diseases. Based on the therapeutic success of human immunodeficiency virus type 1
(HIV-1) PR inhibitors, the proteinase (PR) of HTLV-1 is a potential target for
chemotherapy. To facilitate the design of potent inhibitors, the subsite
specificity of HTLV-1 PR was characterized and compared to that of HIV-1 PR. Two
sets of substrates were used that contained single amino-acid substitutions in
peptides representing naturally occurring cleavage sites in HIV-1 and HTLV-1. The
original HIV-1 matrix/capsid cleavage site substrate and most of its substituted
peptides were not hydrolyzed by the HTLV-1 enzyme, except for those with
hydrophobic residues at the P4 and P2 positions. On the other hand, most of the
peptides representing the HTLV-1 capsid/nucleocapsid cleavage site were
substrates of both enzymes. A large difference in the specificity of HTLV-1 and
HIV-1 proteinases was demonstrated by kinetic measurements, particularly with
regard to the S4 and S2 subsites, whereas the S1 subsite appeared to be more
conserved. A molecular model of the HTLV-1 PR in complex with this substrate was
built, based on the crystal structure of the S9 mutant of Rous sarcoma virus PR,
in order to understand the molecular basis of the enzyme specificity. Based on
the kinetics of shortened analogs of the HTLV-1 substrate and on analysis of the
modeled complex of HTLV-1 PR with substrate, the substrate binding site of the
HTLV-1 PR appeared to be more extended than that of HIV-1 PR. Kinetic results
also suggested that the cleavage site between the capsid and nucleocapsid protein
of HTLV-1 is evolutionarily optimized for rapid hydrolysis.
PMID- 11012684
TI - Combinatorial mutagenesis and pseudorevertant analysis to characterize regions in
loop E of the CP47 protein in Synechocystis sp. PCC 6803.
AB - Deletion of the I265-F268 and T271-K277 regions in the large lumenally exposed
loop of the CP47 protein are known to lead to a loss of photoautotrophic growth.
Here, these regions have been investigated by combinatorial mutagenesis and
pseudorevertant mapping. No single amino-acid residue in the I265-F268 region was
found to be critical for function, but a large hydrophobic residue at position
267 and preferentially an aromatic residue at position 268 appeared to be
required for photoautotrophic growth. Starting from an obligate
photoheterotrophic mutant lacking the T271-K277 region, photoautotrophic
pseudorevertants were generated with short in-frame tandem repeats near the site
of the original deletion, partially or fully restoring the length of the original
protein. These pseudorevertants were sensitive to oxygen indicating that the T271
K277 region may provide PS II stability and/or protection against oxygen
dependent photoinactivation. Pseudorevertants with much improved photoautotrophic
growth were also generated for one of the combinatorial mutants in the I265-F268
region. Surprisingly, the secondary mutations in these pseudorevertants mapped to
the ferrochelatase gene. We speculate that the secondary mutation in
ferrochelatase gene resulted in altered ferrochelatase activity. Decreased heme
(phycobilin) biosynthesis and/or increased chlorophyll biosynthesis could then
lead to improved PS II performance of the combinatorial CP47 mutant.
PMID- 11012685
TI - Microheterogeneity of recombinant human phenylalanine hydroxylase as a result of
nonenzymatic deamidations of labile amide containing amino acids. Effects on
catalytic and stability properties.
AB - The microheterogeneity of recombinant human phenylalanine hydroxylase (hPAH) was
investigated by isoelectric focusing and 2D electrophoresis. When expressed in
Escherichia coli four main components (denoted hPAH I-IV) of approximately 50 kDa
were observed on long-term induction at 28-37 degrees C with isopropyl thio-beta
D-galactoside (IPTG), differing in pI by about 0.1 pH unit. A similar type of
microheterogeneity was observed when the enzyme was expressed (1 h at 37 degrees
C) in an in vitro transcription-translation system, including both its
nonphosphorylated and phosphorylated forms which were separated on the basis of a
difference in mobility on SDS/PAGE. Experimental evidence is presented that the
microheterogeneity is the result of nonenzymatic deamidations of labile amide
containing amino acids. When expressed in E. coli at 28 degrees C, the percentage
of the acidic forms of the enzyme subunit increased as a function of the
induction time with IPTG, representing about 50% on 8 h induction. When the
enzyme obtained after 2 h induction (containing mainly hPAH I) was incubated in
vitro, its conversion to the acidic components (hPAH II-IV) revealed a pH and
temperature dependence characteristic of a nonenzymatic deamidation of asparagine
residues in proteins, with the release of ammonia. Comparing the
microheterogeneity of the wild-type and a truncated form of the enzyme expressed
in E. coli, it is concluded that the labile amide groups are located in the
catalytic domain as defined by crystal structure analysis [Erlandsen, H.,
Fusetti, F., Martinez, A., Hough, E., Flatmark, T. & Stevens, R. C. (1997) Nat.
Struct. Biol. 4, 995-1000]. It is further demonstrated that the progressive
deamidations which occur in E. coli results in a threefold increase in the
catalytic efficiency (Vmax/[S]0.5) of the enzyme and an increased susceptibility
to limited tryptic proteolysis, characteristic of a partly activated enzyme. The
results also suggest that deamidation may play a role in the long term regulation
of the catalytic activity and the cellular turnover of this enzyme.
PMID- 11012687
TI - The International Haemophilia Training Centres of the World Federation of
Hemophilia: a 30-year review.
PMID- 11012686
TI - Potency and selectivity of inhibition of cathepsin K, L and S by their respective
propeptides.
AB - The prodomains of several cysteine proteases of the papain family have been shown
to be potent inhibitors of their parent enzymes. An increased interest in
cysteine proteases inhibitors has been generated with potential therapeutic
targets such as cathepsin K for osteoporosis and cathepsin S for immune
modulation. The propeptides of cathepsin S, L and K were expressed as glutathione
S-transferase-fusion proteins in Escherichia coli. The proteins were purified on
glutathione affinity columns and the glutathione S-transferase was removed by
thrombin cleavage. All three propeptides were tested for inhibitor potency and
found to be selective within the cathepsin L subfamily (cathepsins K, L and S)
compared with cathepsin B or papain. Inhibition of cathepsin K by either
procathepsin K, L or S was time-dependent and occurred by an apparent one-step
mechanism. The cathepsin K propeptide had a Ki of 3.6-6.3 nM for each of the
three cathepsins K, L and S. The cathepsin L propeptide was at least a 240-fold
selective inhibitor of cathepsin K (Ki = 0.27 nM) and cathepsin L (Ki = 0.12 nM)
compared with cathepsin S (Ki = 65 nM). Interestingly, the cathepsin S propeptide
was more selective for inhibition of cathepsin L (Ki = 0.46 nM) than cathepsin S
(Ki = 7.6 nM) itself or cathepsin K (Ki = 7.0 nM). This is in sharp contrast to
previously published data demonstrating that the cathepsin S propeptide is
equipotent for inhibition of human cathepsin S and rat and paramecium cathepsin L
[Maubach, G., Schilling, K., Rommerskirch, W., Wenz, I., Schultz, J. E., Weber,
E. & Wiederanders, B. (1997), Eur J. Biochem. 250, 745-750]. These results
demonstrate that limited selectivity of inhibition can be measured for the
procathepsins K, L and S vs. the parent enzymes, but selective inhibition vs.
cathepsin B and papain was obtained.
PMID- 11012688
TI - Total joint arthroplasty in haemophilia.
AB - In severely affected haemophilic patients arthropathy is a common problem which
can lead to considerable pain and functional deficit. Surgical management,
including total joint arthroplasty, can be undertaken if conservative management
fails. A search of the literature showed that a number of studies describing the
use of total knee arthroplasty (TKA) and total hip arthroplasty (THA) in
haemophilia have been published, whereas shoulder, elbow and ankle arthroplasties
are confined to case reports. This paper reviews the functional outcome of
arthroplasty in the different joints, the postoperative and long-term
complications, and the impact of HIV. Although complications are commonly
described and the surgery is technically demanding, the results suggest that
arthroplasty, particularly of the hip and knee, can be a valuable option in the
management of severe haemophilic arthropathy.
PMID- 11012689
TI - Porcine factor VIII provides clinical benefit to patients with high levels of
inhibitors to human and porcine factor VIII.
AB - The development of an inhibitor against Factor VIII is an important complication
of haemophilia and occurs in approximately 31% of patients [1]. Despite various
approaches to their management, the presence of these inhibitors remains a major
cause of morbidity and mortality. Inhibitors may be low level [<5 Bethesda Units
(BU)] or high level [>10 BU]. Low-level inhibitors usually remain low and do not
respond to administered factor VIII with a rise of the inhibitor titre; high
level inhibitors, in contrast, are characterized by a rapid rise in titre
following treatment with factor VIII. Modalities of treatment of acute bleeding
episodes in patients with inhibitors include 'overcoming' the inhibitor with very
large doses of factor VIII, 'bypassing' the inhibitor blockade with products such
as activated prothrombin complex concentrates or recombinant factor VIIa,
'removing' the inhibitor by plasmapheresis or immunoabsorption and 'repressing'
it with immunosuppressive drugs and immune tolerance induction. An alternative
approach is to use a porcine factor VIII concentrate which does not cross-react
with the human factor VIII inhibitor. Following treatment with porcine factor
VIII, functional factor VIII can be detected and the therapeutic levels correlate
with cessation of bleeding. The use of porcine factor VIII may, however, result
in the development of antiporcine factor VIII antibodies, limiting its use.
Experience in patients with high-titre inhibitors indicates that porcine factor
VIII therapy could be used in the presence of factor VIII inhibitors [2-11],
including inhibitors to porcine factor VIII [5,7], and that haemostasis may be
obtained in the absence of detectable levels of circulating factor VIII [7,11].
PMID- 11012690
TI - Protease inhibitor therapy and bleeding.
AB - Shortly after the introduction of protease inhibitor drugs (PIs) for the
treatment of human immunodeficiency virus infection an association between these
drugs and an increased bleeding tendency in patients with hereditary bleeding
disorders was observed. Not only do patients experience an increased bleed
frequency in usual sites, but bleeds can also occur in unusual places such as the
finger joints. Mucus membrane bleeding and haematuria are also common. Ritonavir
appears to be associated with the highest risk of bleeding followed by indinavir.
As yet there has not been enough experience with the newer PIs to assess fully
their potential to induce increased bleeding, although nelfinavir seems to pose
less of a risk than the original PIs. PI-associated bleeds tend to be more
resistant to factor concentrate treatment and periods of prophylaxis may be
required in individuals with frequent persistent bleeds. Patients continuing on
PI therapy tend to develop a tolerance to this adverse effect with time. The
mechanism of the bleeding tendency has not been elucidated. There is no
consistent evidence of a disturbance of coagulation, fibrinolysis or platelet
function which raises the possibility that PIs may exert a direct local effect on
blood vessels. It is very important that this class-specific side-effect is
recognized and understood by both treaters and patients.
PMID- 11012691
TI - The economics of bleeding disorders.
PMID- 11012693
TI - Combined factor V and VIII deficiency in Indian population.
AB - The clinical and haematological heterogeneity in cases of the rare combined
factor V and VIII deficiency has not been reported so far from India. Nine such
cases belonging to five unrelated families have been analysed in the present
study for the various haematological and clinical parameters. A very mild
clinical presentation is seen in all these cases. The clinical manifestations,
however, do not correlate with the plasma levels of these factors.
PMID- 11012692
TI - Haemophilia care in central Scotland 1980-94. I. Demographic characteristics,
hospital admissions and causes of death.
AB - To estimate the resources required to manage patients with haemophilia in
Scotland, we studied the demographic features, hospital admissions and causes of
deaths for individuals with haemophilia A and B and von Willebrand disease,
treated with blood products, during the period 1980-94 living in central
Scotland. Data were obtained from 413 adults and children (93% ascertainment).
The age distribution in 1980 revealed a paucity of individuals over 60 years but
the number in this age group increased over the study period. Of those with
haemophilia A and B, 63 and two respectively, became HIV positive. Hospital
admissions rose from 103 to 168 per annum; the number of annual bed days utilized
also increased, but there was marked annual fluctuation (790-1832). The rate of
admission was greater for those with severe haemophilia A and this increased
during the 15-year period mainly due to the clinical consequences of human
immunodeficiency virus (HIV) and hepatitis C virus (HCV). The admission rate for
haemophilia B was significantly lower than that for haemophilia A, and was
similar for all degrees of severity of the disorder. Throughout the 15-year
period the incidence of admissions for acute bleeds was constant, as was the
average duration in hospital. For those with a factor VIII inhibitor, the rate of
admission was about double the rate of those without an inhibitor, although the
duration of hospital stay was similar for both groups. There were 61 deaths; the
death rate increased during the study period principally due to HIV and HCV, and
12 patients died from haemorrhage. We conclude that: (i) the life expectancy for
haemophiliacs in Scotland was generally increasing, although HIV and HCV caused
increasing mortality and morbidity (as shown by the increase in hospital
admissions); (ii) hospital bed usage for the treatment of acute bleeds continued
to be required, but fluctuated greatly; and (iii) the clinical impression that
haemophilia B is less clinically severe than haemophilia A is confirmed by
objective data. The planning implications for haemophilia care in Scotland and
similar countries are discussed.
PMID- 11012694
TI - Seventeen years' experience with Autoplex/Autoplex T: evaluation of inpatients
with severe haemophilia A and factor VIII inhibitors at a major haemophilia
centre.
AB - A retrospective case analysis of the use of Autoplex T (anti-inhibitor coagulant
complex [heat treated]) at a major haemophilia treatment centre is described.
Twenty-three haemophilia A patients with a history of high-titre (>10 BU), high
response inhibitors were treated for a total of 54 bleeding episodes requiring
hospital admission and/or surgical intervention. Effective or partially effective
haemostatic control was achieved within 72 h in 94% of reported cases (effective
85%; partially effective 9%). The incidence of adverse reactions was low and
there were no thrombotic complications. In bleeding episodes for which BU titres
were determined within 6 months pre- and 6 months post-treatment, there was
little tendency for Autoplex T to cause an anamnestic response (1 of 19 bleeding
episodes). In the three invasive surgical procedures included in the case review,
coverage with Autoplex T resulted in no postoperative complications, no bleeding
at the surgical site, and no postoperative haematoma. The results support the
efficacy and safety of Autoplex T in the treatment of bleeding episodes and
haemostatic coverage of surgical procedures in haemophilia A patients with
inhibitors.
PMID- 11012695
TI - In vitro stability of recombinant human factor VIII (Recombinate).
AB - Factor VIII (FVIII) is currently administered in diverse settings and by a range
of methods, and it is important that the stability of specific FVIII preparations
be documented for these varying uses. This study of Recombinate recombinant human
FVIII (rhFVIII) evaluated: (i) thermostability; (ii) photostability; (iii)
stability during simulated continuous infusion; and (iv) stability after
dilution. This evaluation was conducted over a range of initial rhFVIII potencies
and under differing conditions of temperature, light exposure, dilution and
heparin usage. FVIII biological activity was measured by one-stage and
chromogenic substrate assays. Microbiological assessment was also performed.
Lyophilized rhFVIII was found to be highly thermostable, as evidenced by an
energy of activation (Ea) of 16.2 kcal mol-1 and recovery of 99.3% of initial
activity after incubation for 6 months at 40 degrees C and 93.8% at 60 degrees C
for 2 months. No significant loss of activity could be detected after accelerated
simulated natural daylight exposure of lyophilized rhFVIII, although partial
activity loss was observed after similar exposure of reconstituted rhFVIII.
Shielding in foil wrap effectively prevented such photodegradation of
reconstituted rhFVIII. Based upon these results, exposure of lyophilized rhFVIII
to sunlight is unlikely to affect stability adversely. Activity of reconstituted
rhFVIII (22-106 IU mL-1) remained stable during simulated continuous infusion for
96 h at ambient (20-25 degrees C) and elevated (28-32 degrees C) temperature, and
in the presence or absence of 1 U mL-1 heparin. After dilution of reconstituted
rhFVIII, an immediate 14-42% loss of expected rhFVIII activity was observed
depending upon diluent composition. Accordingly, potential partial loss of
rhFVIII activity should be taken into account when dilution is being considered.
rhFVIII remained sterile at least 96 h during simulated continuous infusion.
rhFVIII is a robust preparation exhibiting biological stability under a wide
array of clinically relevant conditions.
PMID- 11012696
TI - Immune tolerance in a haemophilia A patient with high inhibitor using locally
prepared lyophilized cryoprecipitate.
AB - The immune tolerance in a 12-year-old haemophilia A patient was carried out at
the Faculty of Medicine, Ramathibodi Hospital, Bangkok in 1998. His inhibitor
titres ranged from 10 to 3450 Bethesda units (BU). He suffered from serious
bleeding episodes requiring prolonged hospitalization and the disarticulation of
the left knee joint. After obtaining informed consent, locally prepared
lyophilized cryoprecipitate (LC), heat treated at 60 degrees C for 25 h, was
given in a dose of 13 units kg-1 body weight of factor VIII three times per week.
His inhibitor was increased from 15 to 580 BU within the first 4 weeks of immune
tolerance. Finally, it was decreased to 40 BU in the 36th week. The only adverse
effect was seroconversion of anti-hepatitis C virus after receiving 108 bottles
of LC for 36 weeks. In conclusion, the locally prepared LC was able to control
the bleeding episodes in a haemophilia A patient with high inhibitor. To our
knowledge, this is the first reported case in Thailand.
PMID- 11012697
TI - Immune tolerance for haemophilia patients with inhibitors: analysis of the
western United States experience. The Tri-Regional Nursing Group.
AB - The experience with immune tolerance (IT) induction therapy for haemophilia
patients with inhibitors, instituted during 1990-97 at 17 haemophilia treatment
centres in the western United States, was reviewed. IT was instituted in 104 of
139 (75%) of all identified haemophilia A and haemophilia B patients with
inhibitors. Doses and schedules for IT varied but most patients were treated with
a daily administration of 25-200 units kg-1 day-1. Successful immune tolerance
(defined as Bethesda Unit titres < 1.0) was achieved in 57 of 81 (78%) patients
who completed therapy. IT success was significantly greater for those patients
with historic titres < 100 BU (P < 0.0003) and those with titres of < 10 BU at
initiation of IT (P < 0.0001). IT success was uniformly achieved in 16 patients
with low to moderate responding inhibitors. IT in infants < 2 years of age was
problematic due to the presence of high titre inhibitors and complications of
venous access. Frequent complications of IT included increased bleeding during
intravenous access device insertion (20%) and infections associated with venous
access devices (64%). IT is widely accepted as a treatment modality for
haemophilia patients with inhibitors. Patient participation in IT regimens and
management during therapy is facilitated greatly by the efforts of treatment
centre nurse coordinators who are knowledgeable about haemophilia and its
complications. Additional clinical trials will be necessary to define better
initial dose, schedule, dose adjustment and success/failure criteria for IT.
PMID- 11012698
TI - Proposal of a standard approach to dental extraction in haemophilia patients. A
case-control study with good results.
AB - We found no case-control studies on dental extraction in haemophilia patients in
the literature even though the use of antifibrinolytic agents following a single
infusion of factor VIII or IX has been accompanied by a lower number of bleeding
complications in dental extractions. In this study we verified the incidence of
bleeding complications after dental extraction in a group of 77 haemophilia
patients. One hundred and eighty-four male patients requiring dental extraction
represented the control group. All haemophilia patients received 20 mg kg-1 of
tranexamic acid and a single infusion of factor VIII or IX to achieve a peak
level about 30% of factor VIII or IX in vivo prior to dental extraction. Forty
five of 98 (45.9%) dental extractions in haemophilia patients and 110 of 239
(46%) dental extractions in the control group were surgical ones. We registered
two bleeding complications in the group of haemophilia patients (one late
bleeding and one haematoma in the site of the anaesthetic injection) and one (a
late bleeding) in the control group. The difference of bleeding complications in
the two groups of patients were not statistically significant (P=0.2; OR 0.2; CI
0.01-2.22). The protocol proposed in this study, characterized by the feasibility
and the number of haemorrhagic complications not different from normal
population, make dental extractions in haemophilia patients possible on an out
patient basis with a cost reduction for the community and minor discomfort for
the patients.
PMID- 11012699
TI - Participation in sports by Dutch persons with haemophilia.
AB - Patients with haemophilia are now widely advised to participate in sports.
However, no extensive data are available about their actual participation. A self
administered questionnaire was used to investigate sports participation by
persons with haemophilia in the Netherlands. All 293 questionnaires that were
distributed have been returned; 217 were from people with severe haemophilia A or
B (this is 40% of the severely affected Dutch population with haemophilia). Of
this group, 155 (71%) participate in one or more sports: 66 swim, 36 cycle, 21
play tennis, 18 do fitness exercises, 16 ice skate, 10 ski and 10 play table
tennis; in total 44 different sports are mentioned. Of a group of 16 persons with
haemophilia who are unable to run, 10 (63%) participate in sport and of a group
of 91 who can only run sometimes, 64 (70%) engage in sports. This shows that
there are ample opportunities for persons with haemophilia to participate in
sports, even if they are unable to run. Severely affected persons with
haemophilia are as active as the general Dutch population; in fact, a higher
proportion swims and/or cycles. In conclusion, sports participation in the
Netherlands by persons with haemophilia is in accordance with World Federation of
Hemophilia directives.
PMID- 11012700
TI - Isotopic synovectomy with P-32 in paediatric patients with haemophilia.
AB - Isotopic synovectomy is being proposed as an option in the treatment of patients
with haemophilic arthropathy. We present our experience with 11 paediatric
patients who underwent 17, P-32 isotopic synovectomies for chronic haemophilic
arthropathy. P-32 was injected into the joint per protocol, approved by the
institutional review board. All our patients were male. Nine were factor VIII and
two were factor IX deficient. The following joints were treated: ankle (n=10
procedures), elbow (n=5) and knee (n=2). The first procedure was performed on
December 1993. None were human immunodeficiency virus positive. Mean age at the
first procedure was 10.8 years (range, 5.2-15.2 years). Mean pretreatment joint
clinical scores using the World Federation of Hemophilia guidelines for the ankle
was 5.5 (SD +/- 2.3), the elbow 4.2 (+/-2.5), and knee 5.5 (+/-3.5); the
corresponding post-treatment scores were 2.6 (+/-2.0), 1.4 (+/-0.5) and 2.5 (+/
3.5) respectively. Presynovectomy mean radiological scores using the Pettersson
method were: ankle 1.8, elbow 1.8, and knee 1.5. A scoring system used in our
centre for evaluating joints using magnetic resonance imaging (MRI) gave the
following mean pretreatment scores: ankle 9.5, elbow 8.4, and knee 5.0. A marked
decrease (an 80-100% decrease) in bleeding was seen in 13 of 17 procedures, and a
moderate decrease (51-79% decrease) in two procedures, accounting for 85%
reduction in bleeding into the target joints. The procedure was well tolerated
and no untoward side-effects were noted as of May 1999, with a median follow-up
of 40 months (range 19-65 months). None had any clinical evidence of cancer.
Three patients had their joints retreated [elbow (one), ankle (two)]. These
procedures were also well tolerated. In conclusion, in our study, isotopic
synovectomy using P-32 appears to be feasible, safe and efficacious in the
treatment of haemophilic arthropathy in paediatric patients who have been
followed for a median of 40 months. As previously shown, MRI appears to give more
detailed information about joint arthropathy than plain radiographs.
PMID- 11012701
TI - Elbow joint, crutches and locomotion: special reference to persons with
haemophilia.
AB - A 52-year-old, trans-femoral amputee with haemophilia was hospitalized because of
ambulatory problems arising from the osteo-arthropathic involvement of other
major articulations. Reduced function in the upper limbs, caused by the effects
of recurrent haemarthroses, resulted in additional problems concerning the usage
of auxiliary ambulatory aids. The advantages and disadvantages of traditional and
experimental crutches highlight the functional problems of ambulation in persons
with concomitant upper limb pathologies.
PMID- 11012702
TI - Synovectomy with rifampicine in haemophilic haemarthrosis.
AB - The purpose of this paper was to assess the effectiveness of intra-articular
injected rifampicine in haemophilic patients in order to achieve synovectomy by
preventing repeated intra-articular bleeding. We have used this technique in
haemophilic patients previously and reported our results on 13 cases [1]. Two
hundred and fifty milligrams of rifampicine was injected into the elbow and ankle
joints and 500 mg was injected into knee joints with 3-10 mL of lidocaine,
depending on the joint size. The injections were repeated once a week for 7
weeks. Patients were only covered with antihaemophilic factor on the day of the
injection at 30% above their coagulation level. We evaluated the results using
two measures: subjective reports from the patient and objective assessment by the
examiner. In the subjective reports the patient graded the results from their own
perspective from 1 (poor) to 10 (excellent): 1-3, poor; 4-6, fair; 7-8, good; and
9-10, excellent. In the objective reports the grading was: excellent ('dry
joint', full function, no haemarthrosis, no synovitis); good (clinical
improvement, synovitis, reduction of haemarthroses, full function); fair
synovitis (reduction of haemarthroses, no change in function); poor synovitis
(persistent haemarthroses). This paper reports on the results of 38 patients with
39 joints with more that 3 years follow up, mean 1.8 years. There were 22 knees,
nine elbows and eight ankles. Subjectively, there were excellent results in 21
joints (11 knees, six elbows and four ankles) good results in 15 joints (eight
knees, three elbows and four ankles), fair results in two knees and a poor result
in one knee. Objectively, results obtained were excellent in 20 joints (11 knees,
six elbows and three ankles); good in 17 (nine knees, three elbows and five
ankles); fair in one knee and poor in one knee.
PMID- 11012703
TI - Intra-articular hyaluronic acid in the treatment of haemophilic arthropathy of
the knee. Clinical, radiological and sonographical assessment.
AB - Hyaluronic acid has been used successfully in the treatment of osteoarthritis
since 1989. There is no experience in haemophiliacs in larger study groups. In a
prospective study, 20 patients (21 knees) with haemophilic arthropathy of the
knee received 20 mg hyaluronic acid by intra-articular injection for 5
consecutive weeks. Assessment included clinical scores, X-ray, magnetic resonance
imaging (MRI) and biomechanical motion analysis before and 3 months after the
first injection. The score of the WFH advisory committee and the Aichroth score
for special evaluation of the knee were used. After an average period of 26
months, the World Federation of Hemophilia (WFH) score, the Aichroth score and
the visual analogue scale were evaluated again. All patients had pain caused by
their arthropathy, nine of them had positive antibodies to human immunodeficiency
virus, and 15 had chronic hepatitis C. The mean WFH score was 8.1 points, the
Petterson score was 7.3 points and the Aichroth score was 38 points (maximum 55
points). The WFH score decreased to 7.3 points, the Aichroth score improved to 40
points and the subjective assessment measured with a visual analogue scale
improved from 5.3 to 3.7 points. No differences from MRI controls were detected.
After 3 months, 14 of 20 patients improved subjectively, particularly in longer
walking distance, stair-climbing or initial pain. These positive aspects were
limited by arthropathy in adjacent joints. After 26 months 10 patients still are
benefiting for up to 31 months follow-up. The average WFH score was 7.3 points,
the Aichroth score 39 points, the visual analogue scale 4.0 points. We recommend
hyaluronic acid for haemophilic arthropathy of the knee when regular conservative
therapy has failed and operative treatment is not feasible.
PMID- 11012704
TI - Participation in research: the economic advantages in a haemophilia research
population.
PMID- 11012705
TI - Sensitivity of the reaction time of the resonance thrombogram for factor VIII:C
and factor IX deficiencies in the blood of dogs with haemophilia A or B.
AB - The sensitivity of the reaction time of the resonance thrombogram (RTG-r) was
examined for two instruments based on 105 canine samples with a reduced factor
VIII:C activity and 26 samples with a reduced factor IX activity. These samples
were taken from dogs suffering from haemophilia A (n=18) or B (n=3) before and at
different times after the substitution therapy with fresh frozen plasma. The RTG
r sensitivity was low; with reference to the total of all examined samples, it
was between 0.39 and 0.65 for the factor VIII:C activity and between 0.46 and
0.62 for the factor IX activity, depending on the instrument and the testing
procedure used. Low sensitivity was shown especially by the fact that even some
of the samples with a factor VIII:C activity < 5% showed false negative results.
Moreover, the correlation found between RTG-r and factor VIII:C activity
(Spearman's rank correlation coefficient, r(S)=-0.556 to -0.700) as well as
between factor IX activity and RTG-r (r(S)=-0.380 to -0.612) was only moderate.
The low sensitivity of the RTG towards a reduced activity of the haemophilia
factors VIII:C and IX contradicts the exclusive use of the RTG for monitoring
haemophilic dogs as well as a global screening test for the haemostasis of dogs.
PMID- 11012706
TI - Recombinant FVIIa (NovoSeven) continuous infusion and total hip replacement in
patients with haemophilia and high titre of inhibitors to FVIII: experience of
two cases.
AB - In this report we describe our experience of total hip replacement in two
patients with severe haemophilia A and high titres of inhibitors to FVIII. We
used rFVIIa replacement therapy by continuous infusion to perform the surgery.
The total amount of rFVIIa used in these two patients was very similar but the
manner of administration was quite different. In our experience, it is an
advantage to use a higher dose for shorter periods than a lower dose for a longer
treatment period. Tranexamic acid by continuous infusion, and parallel saline
infusion were useful for good haemostasis and avoided local thrombophlebitis in
the side of rFVIIa infusion.
PMID- 11012707
TI - Cardiac tamponade due to post-cardiac injury syndrome in a patient with severe
haemophilia A and HIV-1 infection.
AB - An 18-year-old man with severe haemophilia A (FVIII:C < 1%) and human
immunodeficiency virus 1 (HIV-1) infection was admitted to the hospital with
fever and chest pain for 7 days. Eight weeks prior to his admission he had an
accident for which he underwent, at another hospital, clinical and laboratory
examination that revealed bone fractures of the nose cavity, and he was given
factor VIII concentrates for seven days due to nasal bleeding. On admission,
chest roentgenogram showed a large cardiac silhouette and echocardiography
confirmed the presence of a large quantity of pericardial fluid. A presumptive
diagnosis of the post-cardiac injury syndrome was made and he was given anti
inflammatory drugs plus infusion of recombinant factor VIII concentrate (35 units
kg-1 b.i.d.). On the seventh day he exhibited cardiac tamponade for which he
underwent subxiphoid pericardiotomy with drainage of approximately 1500 mL of
bloody exudate. He had an uncomplicated recovery and 10 days later he left
hospital. He was given a continuous prophylactic treatment of 15 units kg-1 of
recombinant FVIII every 2 days for 6 months, and 30 months after this episode the
patient is free of any symptom.
PMID- 11012708
TI - Continuous infusion of recombinant activated factor VII during caesarean section
delivery in a patient with congenital factor VII deficiency.
AB - Recombinant activated factor VII (rFVIIa) can be used as an alternative therapy
in patients with FVII deficiency. However, as the drug has a very short half
life, continuous infusion could be a meaningful administration modality. We
report the case of a 30-year-old woman with moderate FVII deficiency and human
immunodeficiency virus infection who underwent a caesarean section delivery. She
was treated with a continuous infusion of rFVIIa and did not suffer any bleeding
complication. The continuous infusion of rFVIIa was a safe and effective
therapeutic approach for our patient, maintaining her levels of FVII:C and
avoiding bleeding during caesarean section and afterwards.
PMID- 11012709
TI - Oral immune tolerance induction to factor VIII via breast milk, a possibility?
PMID- 11012710
TI - Stress and transposable elements: co-evolution or useful parasites?
AB - The activity of transposable elements can be induced by environmental and
population factors and in particular by stresses in various organisms. A
consequence of the increase in transposable element mobility is the creation of
new genetic variability that can be useful in the face of stressful conditions.
In this review, results supporting this hypothesis are presented and discussed.
The main question is how stress induces the activity of transposable elements. We
discuss hypotheses based upon the existence of promoters or fixation sites of
transcription activators in the untranslated regions of transposable elements,
similar to those found in regulatory regions of host defence genes.
PMID- 11012711
TI - Candidate gene analysis of thyroid hormone receptors in metamorphosing vs.
nonmetamorphosing salamanders.
AB - We used two different experimental approaches to test the hypothesis that thyroid
hormone receptor (TR) variation is associated with alternate life cycles modes in
ambystomatid salamanders. In the first experiment, the inheritance of TRalpha and
TRbeta genotypes was determined for metamorphic and non metamorphic offspring
from backcrosses between Ambystoma mexicanum (an obligate metamorphic-failure
species) and metamorphic F1 hybrids (A. mexicanum x A. tigrinum tigrinum). The
segregation of TR genotype was independent of the expression of life cycle mode
phenotype, and neither TR locus was linked to DNA markers that flank a major
effect locus for life cycle mode. In the second experiment, a portion of the
ligand-binding domain of TRalpha and TRbeta was cloned and sequenced for DNA
samples from 14 different ambystomatid salamander populations, including obligate
metamorphic, facultative metamorphic, and obligate metamorphic-failure taxa.
Nucleotide sequence variation was found for both TRalpha and TRbeta, with several
nonsynonomous substitutions that presumably code for nonconservative amino acid
replacements. However, no general relationship was found between TR allelic
variation and life cycle mode among populations or species. These data do not
implicate TRs as candidate loci involved in the current maintenance or past
evolution of alternate life cycle modes in members of the tiger salamander
complex.
PMID- 11012712
TI - The evolution of senescence under curtailed life span in laboratory populations
of Musca domestica (the housefly).
AB - The evolution of senescence may be explained by two different, but not mutually
exclusive, genetic mechanisms. The antagonistic pleiotropy hypothesis predicts
that senescence is a consequence of the fixation of alleles with pleiotropic
effects favouring early life fitness, but bearing a cost in later life. The
mutation-accumulation hypothesis attributes senescence to the accumulation of
deleterious mutations with late-acting effects on fitness in mutation-selection
balance. Experiments were carried out on the housefly, Musca domestica, in which
large and small populations were maintained so that reproduction was limited to
four or five days after reaching sexual maturity. Longevity declined
significantly under the husbandry protocol and was largely the same in large and
small populations; this is consistent with the random accumulation of deleterious
alleles affecting longevity under curtailed life span, although laboratory
adaptation cannot be ruled out entirely as a causal mechanism. An analysis of
life-history data did not provide evidence for a trade-off between longevity and
age at sexual maturity, developmental time, or dry body weight, but there was an
apparent trade-off between longevity and early progeny production, in support of
antagonistic pleiotropy.
PMID- 11012713
TI - Genetic diversity in tetraploid populations of the endangered daisy Rutidosis
leptorrhynchoides and implications for its conservation.
AB - Polyploidy is an important variable in assessing the genetics of endangered plant
species. Species consisting of populations with different chromosome numbers pose
questions as to the mode of inheritance, relative variability status, population
divergence and gene flow. The self-incompatible species Rutidosis
leptorrhynchoides (Asteraceae) in south-eastern Australia is a good example. The
remnant populations in the northern sector of the species range are diploid,
whereas southern ones are either diploid or tetraploid. Allozyme analysis of the
tetraploid populations showed tetrasomic inheritance confirming an autopolyploid
genetic system, a modest increase in their allelic richness over diploid
populations in the same region and a lack of genetic divergence. Conservation and
replenishment strategies should take account of these genetic features of mixed
ploidy.
PMID- 11012714
TI - Transinfection of Wolbachia in the mediterranean flour moth, Ephestia kuehniella,
by embryonic microinjection.
AB - Wolbachia are maternally transmitted intracellular bacteria found in many
arthropod species. They cause a reproductive incompatibility called cytoplasmic
incompatibility (CI) in several hosts, including the Mediterranean flour moth,
Ephestia kuehniella. Two strains of E. kuehniella, one from Yokohama city and the
other from Tsuchiura city, express different levels of CI: the Yokohama strain
expresses CI at a higher level than the Tsuchiura strain. In order to determine
whether the difference of CI levels depends on Wolbachia or the host, we
performed transinfection experiments in E. kuehniella by means of embryonic
microinjection, and successfully transferred Wolbachia carried by the Yokohama
strain into the Tsuchiura strain, from which the original Wolbachia had been
removed by tetracycline treatment. The resulting transinfected strain expressed
CI at a level near that of the Yokohama strain, suggesting that, in these strains
of E. kuehniella, the level of CI is determined by Wolbachia rather than by the
host.
PMID- 11012715
TI - Altitudinal variation for B chromosome frequency in the characid fish Astyanax
scabripinnis.
AB - The analysis of three populations of the characid fish Astyanax scabripinnis
located at different altitudes along the same stream has revealed the presence of
a macro B chromosome in two high-altitude populations (1800 m and 1920 m) but its
absence from a low-altitude population (700 m). Because the stream flows through
very rugged mountains, with numerous falls ensuring that any gene flow occurs
downstream only, the absence of B chromosomes from the low-altitude populations
is best interpreted in the light of the parasitic theory of B chromosome
evolution. Under this theory, we would expect B chromosomes to be more frequent
where environmental conditions are more favourable for the species, because Bs
are best tolerated there. The widespread presence of these B chromosomes in
numerous Brazilian river headwaters, which are the preferred habitat for this
species, support this possibility.
PMID- 11012716
TI - Inter- and intraspecific sexual discrimination in the flour beetles Tribolium
castaneum and Tribolium confusum.
AB - In Tribolium castaneum (CS) and T. confusum (CF), intra- and interspecific rates
of homosexual mounting have been measured. The intraspecific results are
compatible with the hypothesis of both species being sexually indiscriminate.
However, the CF intraspecific rates were very high (35%-53% of mountings were
homosexual), suggesting a lower sexual attractiveness, or a stronger rejection to
being mounted, of CF females relative to conspecific males. CS males discriminate
between species but, in interspecific contacts, preferentially mounted CF males
rather than CF females. CF males do not discriminate between species, but the
loss of sexual attractiveness of CF females, or their rejection to being mounted,
may act as a precopulatory isolation mechanism.
PMID- 11012717
TI - Contact zone between chromosomal races of Mus musculus domesticus. 2. Fertility
and segregation in laboratory-reared and wild mice heterozygous for multiple
robertsonian rearrangements.
AB - Litter size, anaphase I nondisjunction and X-Y dissociation at metaphase I were
studied in homozygous and heterozygous house mice from a central Italian
chromosomal hybrid zone between the CD (2n=22) race and the standard race
(2n=40). We also observed the segregation of the two chromosomal forms
(Robertsonian and non-Robertsonian) in male and female multiple heterozygotes
from the karyotype of their offspring and chromosomal arm counts of metaphase II.
Litter size was significantly reduced in the F1 hybrids, but there was no
difference in litter size between male and female F1s. Fertility in wild mice
decreased with increasing numbers of structural heterozygosities (0-5). Some
metacentrics appear to be under meiotic drive but there was no rule as to which
of the two forms was favoured in backcrosses. An original observation of a
negative correlation between the length of metacentrics and transmission rate was
described in hybrids. Slight cosegregation of chromosomes with a similar
morphology was present in the progeny of males and females. These observations
are discussed in relation to the stability of this hybrid zone through time.
PMID- 11012718
TI - Identification of native and hybrid elms in Spain using isozyme gene markers.
AB - Two elm taxa occur naturally in the Iberian Peninsula: the Field elm (Ulmus
minor) and the Wych elm (U. glabra). In addition, a third taxon, the foreign
Siberian elm (U. pumila), was probably introduced in the 16th century as an
ornamental tree and has spread spontaneously throughout the Peninsula. The
natural hybridization between U. minor and U. pumila produced new individuals
whose morphological traits appear to be mixed. Ulmus pumila, as well as its
hybrids, has a high resistance to Dutch elm disease (DED). For this reason, it is
commonly used in breeding programmes. Extensive hybridization and the high
mortality produced by the last DED epidemic have endangered the conservation of
the native elm. In this study, isozyme analyses are used to characterize the taxa
U. minor and U. pumila. Siberian elms from Spain and China are compared with the
native U. minor. Siberian elm produces isozyme patterns that completely
differentiate it from U. minor. Three loci are completely different between the
species: 6Pgd2, Mdh1 and Prx2. Isozyme markers can also be used to distinguish
native elms from the hybrids that have evolved for generations.
PMID- 11012719
TI - Population genetic structure of Australian magpies: evidence for regional
differences in juvenile dispersal behaviour.
AB - Territorial group size in Australian magpies (Gymnorhina tibicen) ranges from
monogamous pairs to groups of more than 20 individuals. It has been hypothesized
that large territorial groups result from the retention of juveniles after a
breeding effort. If this is true, local populations consisting of large groups
are likely to exhibit the most genetic structure, because over time similar
genotypes will tend to be confined to limited areas if juveniles are
predominantly philopatric. The objective of the present study was to test this
hypothesis using allozyme and mitochondrial DNA data to provide indirect
estimates of regional gene flow (derived from hierarchical population subdivision
analyses). These data were used in combination with estimates of group size to
infer patterns of dispersal among magpie populations across mainland Australia.
Territorial groups were significantly larger in the south-west compared to three
eastern regions. Although inferred levels of gene flow were substantial for all
four regions, a striking pattern emerged from both sets of genetic data: more
differentiation was evident among populations in the south-western region than in
any eastern region. We conclude that levels of juvenile dispersal influence group
size in G. tibicen, because in the south-western region where groups were
largest, populations were most genetically differentiated. Our results suggest
that contrasting population genetic structures may develop within a single
species as a result of differences in social system.
PMID- 11012720
TI - Negative genetic correlation between traits of the Drosophila head, and
interspecific divergence in head shape.
AB - For morphological traits that are negatively correlated, the genetic correlation
(rg) between them might strongly influence patterns of morphological divergence
and shape. Here, the pattern of divergence between two sibling species of
cactophilic Drosophila, D. buzzatii and D. koepferae, is examined for two traits
that are known to be negatively correlated in other Drosophila species: face
width (FW) and width of both eyes (EW). Head width (HW, the sum of FW and EW, i.
e. the total width of the head capsule) was also examined. Genetic and phenotypic
correlations were estimated in the laboratory G2 generation of a sample of wild
D. buzzatii derived from a population where D. koepferae is not present.
Phenotypic correlations were also estimated in D. buzzatii and D. koepferae from
another, very different, population where the species are sympatric. Consistent
with studies in other Drosophila species, rg was negative and significant for the
correlation between FW and EW, and positive (but nonsignificant at a matrix-wide
P-value of 0.05) for the correlations of HW with both FW and EW. This well
defined correlation pattern was also consistent with the phenotypic correlations
in both D. buzzatii and D. koepferae. No significant difference in these traits
was detected between D. buzzatii populations, but head shape has diverged between
D. buzzatii and D. koepferae. Specifically, the two negatively correlated traits,
FW and EW, have evolved in opposite directions in these two species, with HW
showing no significant interspecific difference. The overall picture of this
divergence pattern shows a striking concordance with the present evidence of
negative correlations between FW and EW, and is consistent with the notion of rg
related constraints on the pattern of interspecific differentiation.
PMID- 11012722
TI - Wolbachia segregation rate in Drosophila simulans naturally bi-infected
cytoplasmic lineages.
AB - Wolbachia are maternally transmitted endocellular bacteria infecting several
arthropod species. In order to study Wolbachia segregation rate, Drosophila
simulans females from an Indo-Pacific population (Seychelles) bi-infected by the
two Wolbachia variants wHa and wNo were backcrossed to uninfected males in two
conditions. In the first case, Seychelles males from a stock cured from its
Wolbachia by tetracycline treatment were used. In the second case, the males came
from a naturally uninfected Tunisian population. It was found that (i) the two
Wolbachia variants can segregate, so that bi-infected females can produce a few
offspring infected only by wHa or wNo. This occurs in both backcross conditions.
(ii) Segregation leads more frequently to wHa than to wNo mono-infection. (iii)
Wolbachia transmission is lower when the Seychelles genome is introgressed by the
Tunisian genome, suggesting that host genomic factors might influence infection
fate.
PMID- 11012721
TI - Genetics of alpha-amanitin resistance in a natural population of Drosophila
melanogaster.
AB - The genetic basis of variation in resistance to natural toxins is of interest for
both ecological and evolutionary genetics. The wide variety of larval resources
used by Drosophila, both within and between species, makes flies an excellent
system for studying causes and consequences of selection resulting from exposure
to natural toxins associated with different resources. In this study we carry out
a genetic analysis of alpha-amanitin resistance in a population sample of
Drosophila melanogaster. Data from mapping crosses of chromosome III support a
role for a naturally occurring polymorphism in a multidrug resistance gene
(Mdr65A) in alpha-amanitin resistance. However, there are no amino acid
differences between resistant and sensitive chromosomes at Mdr65A. Therefore, if
Mdr65A mutants contribute to the difference between alpha-amanitin-resistant and
alpha-amanitin-sensitive third chromosome lines, the underlying cause is a gene
regulatory mutation.
PMID- 11012723
TI - Physical mapping of rDNA genes, (TTAGGG)n telomeric sequence and other
karyological features in two earthworms of the family Lumbricidae (Annelida:
Oligochaeta).
AB - A cytogenetical study was carried out on the chromosomes and nuclear DNA amounts
of the terrestrial earthworms Octodrilus complanatus and Eisenia foetida
(Annelida: Oligochaeta: Lumbricidae). Chromosomes were studied using Giemsa
staining, banding methods and fluorescent in situ hybridization (FISH) with two
repetitive DNA probes [rDNA and (TTAGGG)n]. rDNA FISH and silver staining
consistently identified one chromosome pair per spread in both species. The
telomeric sequence (TTAGGG)n hybridized with termini of all the chromosomes in
both earthworms. Flow cytometry DNA assays showed that O. complanatus and E.
foetida had different nuclear DNA contents (2C value=1.72 and=1.40 pg,
respectively) but very similar base composition in their genomes.
PMID- 11012724
TI - Chromosomal regions involved in hybrid performance and heterosis: their AFLP(R)
based identification and practical use in prediction models.
AB - In this paper, a novel approach towards the prediction of hybrid performance and
heterosis is presented. Here, we describe an approach based on: (i) the
assessment of associations between AFLP(R) markers and hybrid performance and
specific combining ability (SCA) across a set of hybrids; and (ii) the assumption
that the joint effect of genetic factors (loci) determined this way can be
obtained by addition. Estimated gene effects for grain yield varied from
additive, partial dominance to overdominance. This procedure was applied to 53
interheterotic hybrids out of a 13 by 13 half-diallel among maize inbreds,
evaluated for grain yield. The hybrid value, representing the joint effect of the
genetic factors, accounted for up to 62.4% of the variation in the hybrid
performance observed, whereas the corresponding efficiency of the SCA model was
36.8%. Efficiency of the prediction for hybrid performance was evaluated by means
of a cross-validation procedure for grain yield of (i) the 53 interheterotic
hybrids and (ii) 16 hybrids partly related to the 13 by 13 half-diallel.
Comparisons in prediction efficiency with the 'distance' model were made. Because
the map position of the selected markers is known, putative quantitative trait
loci (QTL) affecting grain yield, in terms of hybrid performance or heterosis,
are identified. Some QTL of grain yield detected in the present study were
located in the vicinity of loci reported earlier as having quantitative effects
on grain yield.
PMID- 11012725
TI - Assessment of genetic variability in a traditional cassava (Manihot esculenta
Crantz) farming system, using AFLP markers.
AB - Despite the urgent need to conserve domesticated plant genetic resources, and
developing 'on farm' strategies of conservation, the impact of traditional
farming practices and of their interaction with ecological factors on the
structure and evolutionary dynamics of the genetic variability of crop
populations has been little documented. We assessed the genetic variability of 31
varieties of cassava (M. esculenta Crantz) traditionally grown by Makushi
Amerindians from Guyana, using AFLP markers. We used a sample of 38 varieties
from an ex situ core collection as a reference. Accessions of wild cassava were
also included. While clonality of the varieties was expected due to the
vegetative propagation of cassava, 21 varieties presented intravarietal
polymorphism. Among the varieties from a single site in Guyana, genetic diversity
was the same as that in the accessions from the core collection. We suggest that
incorporation of volunteer seedlings, produced by sexual reproduction, into the
stock of varieties grown by the Makushi plays a major role in explaining both
intravarietal polymorphism and the high level of genetic diversity. No
correspondence was found between the structure of molecular diversity and
variation observed for agronomic traits that are targets for selection by
cultivators. As found in previous studies, all wild forms of cassava clustered
together and separately from the cultivated varieties in a Neighbour-Joining
dendrogram. These results are consistent with the hypothesis of a limited
domestication event in a restricted area, followed by rapid diffusion of
cultivated phenotypes and convergent evolution. Our results show that local
varieties are an important source of genetic diversity, and highlight the
importance of the interaction between human and ecological factors in the
dynamics of this diversity.
PMID- 11012726
TI - Intratetrad mating, heterozygosity, and the maintenance of deleterious alleles in
Microbotryum violaceum (=Ustilago violacea).
AB - The mating system of Microbotryum violaceum was investigated in populations that
are polymorphic for mating-type bias, where individuals produce viable haploids
of only one of the two required mating types. The cause of mating-type bias was
identified as deleterious recessive alleles linked to mating type. Maintenance of
the deleterious alleles was promoted by early conjugation among products of
single meioses, such that the duration of the free-living haploid stage is
minimized. This development was also observed in nonbiased isolates. As a
consequence, the mating system tends toward mating within the tetrad, which might
be expected to reduce heterozygosity. However, complete centromere linkage of
mating type ensures conjugation between first division meiotic products, such
that mating in M. violaceum is analogous to forms of meiotic parthenogenesis with
first division restitution (i.e. automixis with central fusion). This fungus was
used to test the prediction that this mating system would maintain heterozygosity
in regions of the genome linked to centromeres. Therefore, populations were
screened for additional heterozygous lethal recessive alleles linked to
centromeres, and several examples were found. Furthermore, the occurrence of
intratetrad mating in M. violaceum provides an explanation for low variation
among individuals within populations, inconsistent estimates of outcrossing
rates, low levels of mating between tetrads of one diploid individual, and high
frequencies of haplo-lethal alleles in natural populations.
PMID- 11012727
TI - F1 hybrid inviability in eucalyptus: the case of E. ovata x E. globulus.
AB - The impact of inbreeding and hybridization on fitness was compared in the two co
occurring forest tree species, Eucalyptus ovata and E. globulus, aimed at
explaining the rarity of their hybrids in nature. The success of selfing, open
pollination and outcrossing of both species and interspecific hybridization was
monitored from seed-set to 10-year's growth in a field trial. There was a
unilateral barrier to hybridization with seed-set obtained only with E. ovata
females. The F1 hybrids exhibited reduced viability compared to intraspecific
cross-types at virtually all stages of the life cycle and are clearly at a
selective disadvantage compared with their open-pollinated E. ovata half-sibs
with which they would directly compete in nature. Eucalyptus ovata and E.
globulus overlap in their flowering time but the F1 hybrids flowered later with
virtually no overlap with either species. The asynchronous flowering and reduced
reproductive fitness of F1 hybrids would markedly limit the opportunity for
advanced generation hybridization. Inbreeding similarly had a deleterious effect
on the fitness of both species, and the F1 hybrids were most competitive with the
E. ovata selfs. It is argued that changes in inbreeding levels of parental
populations may be a key factor affecting the relative fitness of hybrids and
their potential to impact on the pure species gene pool. Reduced fitness of the
pure species through inbreeding may result in hybridization having its greatest
evolutionary impact in small founder or relict populations.
PMID- 11012728
TI - Population structure of the pestiferous moth Helicoverpa armigera in the eastern
Mediterranean using RAPD analysis.
AB - The genetic structure of the cotton bollworm, Helicoverpa armigera (Hubner)
(Lepidoptera: Noctuidae), was studied in the eastern Mediterranean. Moths were
sampled in six locations (five in Israel, and one in Turkey) and their genetic
relationship was analysed using RAPD-PCR. Three 10-oligonucleotide primers
revealed 84 presumptive polymorphic loci that were used to estimate population
structure. Results reveal low level of genetic distances among Israeli and
Turkish populations. The estimated values of FST and theta for the eastern
Mediterranean populations were very low across all populations, indicating a high
level of gene flow. Four distinct RAPD-product profile types were defined, and
found in all Israeli and Turkish populations. Although no isolation by
geographical distance was detected, topographical barriers may play a role in
such isolation.
PMID- 11012729
TI - Sex, linkage disequilibrium and patterns of parasitism in three species of
cyclically parthenogenetic Daphnia (Cladocera: Crustacea).
AB - To gain insight into genetic variation for resistance to parasites, this study
assayed clonal variation in cyclically parthenogenetic Daphnia magna with respect
to parasitic infection. Samples were collected from natural populations, and the
allozyme phenotypes of infected hosts were compared to those of uninfected hosts.
Differences between the clonal composition of the infected and uninfected class
were evident in only two of 16 populations examined. This result stands in
contrast to a study of species in the D. pulex and D. longispina species
complexes, where clonal variation for infection was found in 12 of 25 populations
(Little & Ebert, 1999). Considering all populations from both studies,
associations between host genotype and infection were typically evident only in
populations that showed low genotypic diversity and evidence of genetic
disequilibria, with D. magna showing the least amount of disequilibria. This
pattern is compatible with at least two possibly overlapping hypotheses. First,
it may be that those populations lacking clonal variation for infection
experienced weaker parasite-mediated selection. We can not rule out variation in
selection pressure as an explanation, but found no evidence that the prevalence
or intensity of parasitism differed either among species, or between those
populations which showed clonal variation for infection and those that did not.
Second, it could be that some populations, especially those of D. magna, have
more frequent sexual recruitment than others. Sexual recombination breaks up gene
combinations which are in linkage disequilibrium, and our method to detect clonal
variation for resistance relies on linkage between genetic markers (allozymes)
and resistance loci. Past work on Daphnia has shown that the level of sexual
recruitment (which is in turn mediated by habitat permanency) is indeed commonly
linked to the occurrence of genetic disequilibria. Our results may thus
underestimate the prevalence of clonal variation for infection (especially for D.
magna), because most of the populations analysed appeared to have high levels of
sexual recruitment and therefore lacked the linkage disequilibrium that underlies
associations between allozymes and susceptibility.
PMID- 11012731
TI - Distribution of the transposable element mariner in anopheline mosquitoes.
AB - We have surveyed the distribution of the transposable element mariner using PCR
in 23 species of Anopheles mosquitoes, including all of the most important
vectors of malaria in South-east Asia. Sequencing of the nine positive species
revealed elements from the irritans, mauritiana and mellifera subfamilies. These
are the first data showing the presence of three subfamilies of mariners in
anophelines. The elements we encountered are likely to be inactive, based on the
presence of multiple stop codons and/or frameshifts.
PMID- 11012730
TI - Dispersion of the Cf-4 disease resistance gene in Lycopersicon germplasm.
AB - In the past, numerous Cf genes have been reported in tomato (Lycopersicon
esculentum Mill.) that confer resistance against leaf mould (Cladosporium fulvum
Cke.). We are interested in genetic variation at Cf loci. Therefore, previously
uncharacterized Cf genes were further analysed. Recognition of the AVR4 elicitor,
DNA gel blot analysis, PCR analysis and sequencing of part of the Cf-4 locus
showed that a large proportion of the accessions tested harboured the Cf-4
resistance gene. We concluded that despite differences in nomenclature, all these
accessions harbour the same Cf-4 locus, probably introgressed from the same
donor. The origin of the Cf-4 locus and the reasons for discrepancies with
earlier reports are discussed.
PMID- 11012732
TI - The genetic diversity of native, stocked and hybrid populations of marble trout
in the Soca river, Slovenia.
AB - The marble trout (Salmo marmoratus) is an endangered species in Slovenia (and in
Italy, Croatia and Albania) because of hybridization resulting from intensive
stocking. Eleven populations of trout from the Soca river basin (Slovenia) were
analysed using 31 presumptive enzyme loci. Three European control samples
representing the main European genotypes of brown trout were also analysed. This
analysis confirmed the existence of extensive hybridization in the main river,
resulting in an equal mixture of alleles belonging to marble trout, and Danubian
and Atlantic brown trout (Salmo trutta). Despite the high level of introgression
observed in the main Soca River, nearly pure populations of marble trout were
found in the headwaters of five tributaries. The five stations with pure marble
trout will be the basis of a rehabilitation programme. Hardy-Weinberg and linkage
disequilibria were observed and hypotheses are discussed to explain this. A
scenario for the colonization of the Adriatic region is proposed.
PMID- 11012733
TI - The use of molecular markers to investigate the genetic structure of an oil palm
breeding programme.
AB - RFLP markers (40 probes covering 60% of the oil palm genome) have been used to
assess genetic diversity within 54 palms of a specific oil palm breeding
programme. A further 10 palms encompassing a broader range of origins were also
included to provide a wider framework for comparative analysis. These palms
represent a majority of the parents in a crossing programme which aims to combine
the best features of African tenera germplasm with South-east Asian Deli dura
material. Progeny from these crosses are planted in up to six sites on three
continents, where the palms are being assessed in detail for yield components. A
total of 157 RFLP bands were scored and the data analysed by calculating genetic
distances according to Nei & Li, and by correspondence and cluster analysis. The
relationships that emerge through this molecular analysis correspond well with
known pedigree and provenance. For example, south-east Asian Deli dura material
forms a cluster clearly distinct from AVROS pisifera gene pools, and a selection
of African breeding material forms a further and broader grouping. The potential
ability of markers to assist in oil palm breeding through examination of the
genetic structure of crossing programmes is discussed, as is their value in
parental selection to maintain residual diversity within specific breeding pools
and use in evaluating the fidelity of breeding lineages.
PMID- 11012734
TI - The effect of drought stress on inbreeding depression in four populations of the
Mediterranean outcrossing plant Crepis sancta (Asteraceae).
AB - The effect of physiological stress on the magnitude of inbreeding depression in
plants has been the subject of few studies and is currently controversial because
of contradictory results. We measured the inbreeding depression at three drought
stress levels, precisely defined by a preliminary physiological experiment. We
also tested the hypothesis that more highly self-compatible populations exhibit
reduced inbreeding depression due to purging of deleterious mutations. The study
was conducted on two populations of the annual and allogamous plant Crepis sancta
collected from the French Mediterranean region and two other populations from
marginal areas with various self-incompatibility levels. Drought stress did not
increase inbreeding depression in terms of plant mortality but significantly
increased the inbreeding depression for the date of first flowering, number of
heads per plant and relative growth rate. The most self-fertile marginal
population showed an absence of inbreeding depression in most of the measured
traits indicating that purging could have taken place in this population. The
three others populations showed relatively low and similar estimates of
inbreeding depression (delta approximately 0.35). The relatively low values
obtained compared to the results found in allogamous plants suggests that the
absence of competition for C. sancta in our experiment probably underestimated
the effects of inbreeding in natural populations where competition occurs.
PMID- 11012735
TI - Hyperplastic polyps and DNA microsatellite unstable cancers of the colorectum.
AB - Although the scientific and clinical rationale for classifying colorectal cancer
according to mechanisms underlying genetic instability is well supported, little
is known of the early morphogenesis of sporadic cancer showing high levels of DNA
microsatellite instability (MSI-H). Evidence is accumulating that the traditional
adenoma-carcinoma sequence may not apply to sporadic MSI-H colorectal cancer. The
serrated pathway comprising hyperplastic polyps, mixed polyps and serrated
adenomas may serve as the missing link. This review relates the recently
described CpG island methylator phenotype (CIMP) to the serrated pathway. Two
rate-limiting genetic steps may underlie the neoplastic pathway associated with
CIMP. A transmembrane receptor expressed by pericryptal myofibroblasts (HPP1) may
be implicated in the transition from normal to hyperplasia whereas inactivation
of hMLH1 is responsible for the conversion of hyperplasia to dysplasia through
loss of DNA mismatch repair. These mechanisms fit with clinical observations
relating to sporadic MSI-H colorectal cancer, specifically proximal location,
multiplicity, higher frequency among females and rapid evolution of early cancer.
PMID- 11012736
TI - Expression of promyelocytic leukaemia protein in thyroid neoplasms.
AB - AIMS: Promyelocytic leukaemia protein (PML) is an oncoprotein involved in the
pathogenesis of acute promyelocytic leukaemia and is localized in distinct PML
nuclear bodies. Our previous observation of overexpression of the PML in hormone
sensitive normal tissues and malignant solid tumours, including the thyroid, led
to this analysis of the PML expression in various thyroid neoplasms to
characterize the importance of the PML in thyroid carcinogenesis. METHODS AND
RESULTS: Immunohistochemistry was performed on paraffin-embedded tissue samples
from 106 thyroid neoplasms after antigen retrieval by microwave. Immunoblotting
was done with fresh frozen tissues in a few tumours. The PML was strongly
expressed in all papillary carcinomas in diffuse or ball-shaped patterns. In the
follicular neoplasms, the PML expression was variable, but there was no
significant difference between adenomas and carcinomas. In the medullary
carcinomas, the PML expression was either not detectable or was lower than in non
neoplastic thyroids. Quantitatively different expression of the PML in various
thyroid neoplasms was confirmed by immunoblotting. CONCLUSION: A significant
difference of the PML expression according to the type of thyroid neoplasms
suggests that the PML is important in papillary thyroid carcinomas, and
furthermore, that PML expression may be used in differential diagnosis of thyroid
neoplasms.
PMID- 11012737
TI - Epstein-Barr virus in gastric carcinomas with lymphoid stroma.
AB - AIMS: To clarify the relationship between the Epstein-Barr virus (EBV) and
gastric carcinoma with lymphoid stroma (GCLS) in Koreans, and to characterize the
EBV-positive GCLS. METHODS AND RESULTS: EBV infection was examined using EBER in
situ hybridization and polymerase chain reaction in 45 cases of GCLS among
Koreans, and in 292 consecutive cases of gastric carcinomas without lymphoid
stroma (non-GCLS) as controls. EBV infection was found in 30 tumours (67%) of
GCLS and 10 tumours (3.4%) of non-GCLS (P < 0.05). EBV-positive GCLS was more
prevalent in males, poorly differentiated histological type and diffuse type in
Lauren's classification, and tended to be located more in the middle third of the
stomach than EBV-negative GCLS (P < 0.05). p53 overexpression was observed in 22%
of GCLS (17% of EBV-positive GCLS and 33% of EBV-negative GCLS), and 34% of non
GCLS (EBV-positive GCLS vs. non-GCLS: P = 0.056). The survival of the patient
with GCLS was not correlated with EBV infection or p53 immunoexpression (follow
up period: 11-97 months). CONCLUSIONS: GCLS in Koreans is strongly associated
with EBV infection. The prognosis in GCLS is not dependent upon either the status
of EBV infection or the status of p53 immunoexpression.
PMID- 11012738
TI - Congenital gastrointestinal stromal tumour is morphologically indistinguishable
from the adult form, but does not express CD117 and carries a favourable
prognosis.
AB - AIMS: The histological and immunohistochemical features of a congenital stromal
tumour of the jejunum are compared with those of adult gastrointestinal stromal
tumours (GIST). The literature concerning the diagnosis and prognosis of
congenital small intestinal stromal tumours is reviewed. METHODS AND RESULTS: A
term female infant presented with intestinal obstruction, from birth. Histology
of a 15-mm jejunal nodule showed a predominantly spindle-cell tumour with
epithelioid areas. There was a low mitotic count and mild nuclear pleomorphism,
extensive necrosis and haemorrhage, and focal calcification.
Immunohistochemically, tumour cells stained for muscle specific actin and
vimentin. Staining for CD117 (c-kit), S100, desmin and CD34 was negative. The
features were compared to those of seven adult cases: no morphological feature
was specific to the congenital tumour, which was smaller than the adult cases.
There were no ultrastructural features specific for a particular line of
differentiation. Immunohistochemical staining patterns were similar, except for
CD117, which was strongly positive in all adult tumours, but negative in the
congenital tumour. CONCLUSIONS: This congenital jejunal stromal tumour
morphologically resembled adult GIST, but lack of c-kit expression suggests that
it is nosologically distinct. Despite the presence of histological features which
would cause the tumour to be categorized as malignant in an adult, it is apparent
from previous reports of congenital small intestinal stromal tumours that the
prognosis is favourable.
PMID- 11012739
TI - Secondary neoplasms of the male genital tract with different patterns of
involvement in adults and children.
AB - AIMS: The incidence, presentation and macroscopic and histological features of
secondary neoplasms of the male genital tract are described with reference to
their differential diagnosis. METHODS AND RESULTS: A retrospective study of cases
from the Royal London Hospital yielded a total of 31 secondary neoplasms
involving the testis: 14 at postmortem examination and 17 surgical specimens.
Nine cases were leukaemias: six acute lymphoblastic and two acute myeloid
leukaemias in children, and one chronic lymphocytic leukaemia in an adult. The
commonest primary sites of metastases to the testis were prostate (six cases),
stomach (five cases) and lung (three cases). There were two malignant melanomas
and isolated examples of metastases from the adrenal gland (neuroblastoma),
cerebellum (medulloblastoma), soft tissue (alveolar rhabdomyosarcoma), pancreas
and rectum. Of the metastases from solid tumours, 12 involved the right testis
only, three involved the left and four were bilateral. In seven of these cases
there were multiple testicular nodules, in seven there was a single mass, and in
the rest there was diffuse involvement. Secondary neoplasms represented 4.6% of
all testicular neoplasms at autopsy, and 1.6% in surgical specimens. There were
five secondary penile neoplasms: two each from the pancreas and prostate and one
from the bladder. Two neoplasms metastatic to the spermatic cord, both from a
gastric primary, were included in the series. CONCLUSIONS: Secondary neoplasms of
the testis occur with a frequency comparable to other sites in the genitourinary
tract, and metastases to the spermatic cord, epididymis, and penis, are rare in
comparison. Disseminated neoplasms rarely present initially at this site and are
histologically distinctive in adults, but in children they must be distinguished
from primary small round blue cell tumours.
PMID- 11012740
TI - Cutaneous perineurioma: a poorly recognized tumour often misdiagnosed as
epithelioid histiocytoma.
AB - AIMS: Eleven cases of cutaneous perineurioma were studied to further characterize
the histological features of this entity. METHODS AND RESULTS: The histological
and immunocytochemical features of 11 cases of cutaneous perineurioma were
studied and detailed by two pathologists. Clinical data were obtained from the
referring clinician. Seven patients were female and four were male with ages
ranging from 19 to 67 years (median 41 years). Six lesions arose on the leg.
Macroscopically lesions ranged from 4 mm to 14 mm in maximum diameter (median 7
mm). Diagnostic histological features included a nonencapsulated but sharply
demarcated tumour with a dumbbell architecture. The tumour cells were spindle
shaped with delicate inconspicuous cytoplasm and arranged in sheets, whorls or
with a vague fascicular pattern. Epithelioid cells with moderate amounts of
eosinophilic cytoplasm were frequently admixed with the spindle cells. One tumour
had trabeculae of cells embedded within a dense collagenous stroma as described
in sclerosing perineurioma. One case displayed a prominent myxoid stroma. Three
further cases contained small foci of fibrosis or myxoid change suggesting a
morphological spectrum exists in cutaneous perineurioma. Mitoses were
exceptionally rare and necrosis and significant cytonuclear pleomorphism was not
found. All tumours were epithelial membrane antigen (EMA) positive. Six cases
showed focal positivity for factor XIIIa. Follow-up ranged from 5 months to 6
years (median 1 years). No tumour recurred or metastasized. CONCLUSIONS: The
histological appearance of this tumour is broader than hitherto realized. Several
cases in this series were misdiagnosed histologically and cutaneous perineuriomas
may be more common than currently appreciated.
PMID- 11012741
TI - Tamoxifen-associated postmenopausal adenomyosis exhibits stromal fibrosis,
glandular dilatation and epithelial metaplasias.
AB - AIMS: Adenomyosis is relatively rare in postmenopausal women but recent reports
have described its occurrence in this age group in patients taking tamoxifen.
This study describes the pathology of nine cases of adenomyosis in postmenopausal
women who were taking this medication. METHODS AND RESULTS: The pathology of the
nine tamoxifen-associated cases was compared to five cases of postmenopausal
adenomyosis not associated with tamoxifen. Morphological features present within
adenomyosis more often in those taking tamoxifen were cystic dilatation of glands
(which sometimes resulted in grossly visible intramural cystic lesions), fibrosis
of the stroma and various epithelial metaplasias. The proliferative activity
within the adenomyosis, as determined by MIB1 staining, was higher in the
tamoxifen group. CONCLUSIONS: The study supports an association between tamoxifen
therapy and the presence of adenomyosis in postmenopausal women. The
aforementioned morphological features are characteristic of polypoid and
nonpolypoid surface endometrium associated with tamoxifen and their occurrence
within the adenomyosis is likely to represent extension of the surface epithelial
changes. Adenomyosis may be more common than is generally realized in women
taking tamoxifen and may account for postmenopausal bleeding in these patients.
PMID- 11012742
TI - Distribution of apoptotic cells and expression of apoptosis-related proteins
along the intrahepatic biliary tree in normal and non-biliary diseased liver.
AB - AIMS: The cell kinetics and homeostasis of biliary epithelial cells may be
maintained differently along the biliary tree. In this study, the role of
apoptosis in the maintenance and homeostasis of the intrahepatic biliary tree was
evaluated. METHODS AND RESULTS: By counting apoptotic biliary cells and by
immunostaining apoptosis-related proteins in normal liver, fatty liver, and those
with acute viral hepatitis, chronic viral hepatitis, and hepatitis virus-related
cirrhosis, it was found that the larger the intrahepatic bile ducts became, the
more biliary epithelial cells underwent apoptosis. bcl-2, an inhibitor of
apoptosis, was diffusely expressed in the interlobular bile ducts, but rarely
detectable in the large and septal bile ducts. bcl-XL and mcl-1, inhibitors of
apoptosis, and bax, a promoter of apoptosis, were diffusely expressed along the
intrahepatic biliary tree. CD95, a direct inducer of apoptosis, was present in
the large and septal bile ducts, but rarely in the interlobular bile ducts.
CONCLUSION: The ratio of bax to bcl-2, as well as the expression of CD95 which
differed at the interlobular versus large and septal bile ducts, may be
responsible for the unique distribution of apoptotic biliary cells and involved
in the homeostasis of the intrahepatic biliary tree.
PMID- 11012743
TI - Changing patterns of histological subgroups during therapy of Ph1+ chronic
myelogenous leukaemia.
AB - AIMS: Bone marrow histopathology reveals a striking heterogeneity at diagnosis of
Philadelphia chromosome positive (Ph1+) chronic myelogenous leukaemia (CML).
Based on semiquantitative evaluations of the number of megakaryocytes and the
content of fibres, various histological subtypes have been postulated. However,
little information exists on whether these groups represent stable categories of
the different classification systems and whether therapeutic regimes exert any
influence on the putative shift of histological patterns. METHODS AND RESULTS: A
retrospective clinicopathological study was performed on 396 bone marrow biopsies
derived from 173 patients. There were at least two representative trephines taken
at diagnosis and at median intervals of 16 months. Processing of the specimens
involved immunostaining with CD61 (megakaryopoiesis) and Ret40f (erythropoiesis)
and Gomori's silver impregnation technique. Based on morphometric analysis and in
accordance with the general appearance of bone marrow histology three different
histological subtypes were distinguished. These consisted of a granulocytic (51
patients), a predominantly megakaryocytic (73 patients) and a myelofibrotic
pattern (49 patients). Follow-up biopsies revealed that a significant transition
of histological groups occurred and that, independently of treatment modalities,
the myelofibrotic category was associated with an unfavourable prognosis. Of the
124 patients without myelofibrosis at onset, 42% later transformed into the
myelofibrotic subtype. However, these patients showed no prevalence of either a
pre-existing granulocytic or megakaryocytic growth. Myelofibrotic changes were
significantly associated with interferon (IFN) and busulfan (BU) therapy. On the
other hand, a transition of a myelofibrotic into a nonfibrotic subtype was
detectable in 17 of the 49 patients under study and related to hydroxyurea (HU)
treatment. CONCLUSIONS: Histological classification systems of bone marrow
features in CML do not represent stable patterns, but may be significantly
altered by therapy, in particular IFN and HU.
PMID- 11012744
TI - Lymphomatous features of aggressive NK cell leukaemia/lymphoma with massive
necrosis, haemophagocytosis and EB virus infection.
AB - AIMS: Aggressive natural killer (NK) cell leukaemia will be categorized as a
distinct entity in the new WHO classification of malignant lymphomas. However,
its non-leukaemic features remain unclear. We therefore investigated the
morphological and immunophenotypic features of this lymphoma. METHODS AND
RESULTS: Four cases with aggressive NK cell lymphoma were morphologically and
immunohistochemically studied. All cases followed an aggressive course with death
occurring within about 3 months of initial presentation. In these cases, the
neoplastic cells disseminated throughout systemic lymph nodes and invaded various
tissues and organs. The lymphoma cells were large cells showing nuclear
irregularity and a pattern of sinusoidal invasion in lymph nodes. Apoptosis and
coagulation necrosis were both frequently observed. Haemophagocytosis was
observed in all cases. Neoplastic cells in paraffin-embedded tissue specimens
from these patients had CD3(CD3epsilon)+ CD56(123C3)+ granzyme+ TIA-1+ EBERT+
CD43(MT1)- CD45RO(UCHL-1)- CD57(Leu7)- CD20(L26)- phenotypes. In the two cases
where tissue was available for immunohistochemical study in frozen sections,
neoplastic cells showed CD56(Leu19)+ perforin+ Fas ligand(FasL)+ CD2(Leu5b)-
CD3(Leu4)- CD4(Leu3)- CD5(Leu1)- CD7(Leu9)- CD8(Leu2)- betaF1- TCRdelta1-
phenotypes. CD16(Leu11b) was positive in one case. CONCLUSIONS: : Natural killer
cell lymphomas appear to represent a non-leukaemic counterpart of aggressive
natural killer cell leukaemia, a relationship similar to that in adult T-cell
leukaemia/lymphoma. Awareness and diagnosis of this aggressive lymphoma is
important because of its fulminant course.
PMID- 11012746
TI - From this month's histopathology
PMID- 11012745
TI - Commentary: aggressive NK cell lymphomas: insights into the spectrum of NK cell
derived malignancies.
PMID- 11012747
TI - Toll-like receptors: molecular mechanisms of the mammalian immune response.
PMID- 11012748
TI - Pollution and the immune response: atopic diseases--are we too dirty or too
clean?
PMID- 11012749
TI - Characterization of CD4- CD8- CD3+ T-cell receptor-alphabeta+ T cells in murine
cytomegalovirus infection.
AB - In this study, we have investigated that after the intraperitoneal infection with
murine cytomegalovirus (MCMV), the CD3+ CD4- CD8-(double negative; DN) T-cell
receptor (TCR)alphabeta+ T cells increased in peritoneal cavity, liver and spleen
in both resistant C57BL/6 and susceptible BALB/c mice. The total cellular
population of these cells showed peak levels around day 5 after infection in all
the three investigated organs and the following phenotypical and functional
characteristics emerged. The peritoneal DN TCRalphabeta+ T cells expressed highly
skewed TCRVbeta8 on day 5 after infection compared with the uninfected mice, but
those in spleen and liver showed moderate and low skewed TCRVbeta8, respectively.
The percentages of NK1.1+ DN TCRalphabeta+ T cells gradually decreased as did
modulation of some of their activation markers consistent with an activated cell
phenotype. The peritoneal DN TCRalphabeta+ T cells on day 5 after infection
expressed the genes of interferon-gamma (IFN-gamma), tumour necrosis factor
alpha, Eta-1 (early T-cell activation-1) and MCP-1 (monocyte chemoattractant
protein 1) but lacked expression of interleukin-4 (IL-4). After in vitro
stimulation with phorbol 12-myristate 13-acetate and calcium ionophore in the
presence of Brefeldin A, higher frequencies of intracellular IFN-gamma+ DN
TCRalphabeta+ T cells were detected in all three investigated organs of infected
mice compared with those of uninfected mice. Stimulation of peritoneal DN
TCRalphabeta+ T cells with plate-bound anti-TCRbeta monoclonal antibodies showed
proliferation and also produced IFN-gamma but not IL-4. These results suggest
that DN TCRalphabeta+ T cells were activated and may have an antiviral effect
through producing IFN-gamma and some macrophage-activating factors during an
early phase of MCMV infection.
PMID- 11012750
TI - Disparate effects of phorbol esters, CD3 and the costimulatory receptors CD2 and
CD28 on RANTES secretion by human T lymphocytes.
AB - This study has examined the stimuli required for secretion of regulated upon
activation, normal T-cell expressed, presumed secreted (RANTES) from T
lymphocytes and found that stimuli such as phorbol 12-myristate 13-acetate (PMA),
which are unable to support T-cell proliferation and interleukin-2 (IL-2)
production, are nevertheless able to elicit strong secretion of RANTES.
Conversely, stimuli such as CD2 and CD28 ligation, which are able to support T
cell proliferation, are unable to elicit RANTES secretion. Coligation of CD3 and
CD28 drives T-cell proliferation to a similar degree as CD2 and CD28 coligation,
yet also supports modest RANTES secretion. Furthermore, CD28 ligation enhances
the secretion of RANTES stimulated by PMA and this costimulatory effect is
abrogated by the phosphoinositide 3-kinase inhibitor wortmannin. Our data also
indicate that the observed effects of PMA on RANTES secretion are probably due to
activation of protein kinase C (PKC) isoenzymes, since RANTES secretion was
unaffected by the non-PKC activating 4alpha-phorbol ester, whilst the general PKC
inhibitor Ro-32-0432 inhibits PMA-stimulated RANTES secretion. Moreover, the
effect of PMA appears to be chemokine-specific because PMA was unable to increase
secretion of the related CC chemokine MIP-1alpha. Under stimulation conditions
where increases in [Ca2+]i occur (e.g. PMA plus ionomycin or CD3 plus CD28
ligation) RANTES secretion can be severely reduced compared with the levels
observed in response to the phorbol ester PMA. Hence, whilst PKC-dependent
pathways are sufficient for strong RANTES secretion, a calcium-dependent factor
is activated which negatively regulates RANTES secretion. This correlates well
with the observation that ligation of cytolytic T lymphocyte-associated antigen-4
(CTLA-4) (expression of which has been reported to be dependent on a sustained
calcium signal), inhibits RANTES secretion induced by CD3/CD28, but has no effect
on PMA-stimulated RANTES secretion.
PMID- 11012751
TI - Activation of T-cell receptor-gammadelta+ cells in the intestinal epithelia of
KN6 transgenic mice.
AB - We analysed the properties of intraepithelial lymphocytes of small intestine (SI
IEL) in KN6-transgenic (Tg) mice expressing cDNA of T-cell receptor (TCR)
gammadelta specific for the T22b molecule. While most splenic Tg TCR-gammadelta+
cells from KN6-Tg mice with H-2d/d background (Tgd/d mice) were Thy-1+ CD8alpha-
CD44dull+ CD45RB+ CD69-, Tg TCR-gammadelta+ cells in SI-IEL (Tg gammadelta-IEL)
were heterogeneous in the expression of Thy-1, CD8alpha and CD44 molecules and
predominantly CD45RB+ CD69+. Tg gammadelta-IEL exhibited a much reduced
proliferative response to the antigen (irradiated H-2b splenocytes) than splenic
Tg TCR-gammadelta+ cells; the CD44+ subset, but not the CD44- subset, in Tg
gammadelta-IEL responded to the antigen. Furthermore, Tg gammadelta-IEL, but not
splenic Tg TCR-gammadelta+ cells, displayed cytolytic activity whether they were
prepared from conventional or germ-free KN6-Tg mice. Comparative analysis of
young and aged KN6-Tg mice revealed that the proportion of CD44+ cells in Tg
gammadelta-IEL increased but the proliferative response of Tg gammadelta-IEL to
the antigen attenuated in association with ageing. Moreover, although Tg
gammadelta-IEL from Tgb/d mice contained a higher proportion of CD44+ cells than
Tgd/d mice, they did not respond to the antigen. These results demonstrate that
Tg TCR-gammadelta+ cells lose the ability to recognize the antigen following
activation in the intestinal epithelia.
PMID- 11012752
TI - Poly-guanosine motifs costimulate antigen-reactive CD8 T cells while bacterial
CpG-DNA affect T-cell activation via antigen-presenting cell-derived cytokines.
AB - Pathogen-derived pattern recognition ligands like lipopolysaccharide (LPS) and
bacterial cytidine-guanosine (CpG)-DNA not only activate dendritic cells and
macrophages but are also mitogenic for B cells. Less clear are the claimed
effects of CpG-DNA on T cells, which range from direct activation, costimulation,
or indirect transient activation via antigen-presenting cell (APC)-derived
interferon type I (IFN type I). Here we demonstrate that CpG-DNA sequence
specifically triggers macrophages to produce IFN type I, interleukin (IL)-12, IL
6 and tumour necrosis factor (TNF), but lacks the ability to directly costimulate
T cells. Strikingly, poly-guanosine (poly-G) extensions to CpG-containing
oligonucleotides (ODN) abolished the macrophage stimulatory potential yet
generated T-cell costimulatory activities. In fact, independently of CpG-motifs,
poly-G-ODN displayed the ability to costimulate T cells. Costimulation was
operative on CD8 T cells but not CD4 T cells. Poly-G-mediated costimulation
resulted in IL-2-driven T-cell proliferation and induced cytolytic T cells.
Overall the data imply that poly-G motifs costimulate antigen reactive CD8 T
cells, while CpG-DNA motifs fail to do so but may affect T-cell activation via
APC derived cytokines such as IFN type I.
PMID- 11012753
TI - Cyclooxygenase-independent inhibition of dendritic cell maturation by aspirin.
AB - When immature human myeloid dendritic cells were differentiated in vitro in the
presence of aspirin, they were unable to stimulate T-cell proliferation. Aspirin
and its major metabolite salicylate changed the surface marker phenotype of
dendritic cells. The drugs particularly suppressed the levels of CD83 and the
secreted p40 unit of interleukin-12 (IL-12), both markers of mature dendritic
cells; 50% inhibitory concentration (IC50) values were 2.5 mM, a concentration
more than 100 times greater than the concentration at mid-point inhibition (ID50)
value for inhibition of prostaglandin synthesis. Concomitantly, the levels of
CD14, a marker of monocytes/macrophages, increased above the levels found in
immature dendritic cells. Cyclooxygenase inhibitors ketoprofen, indomethacin and
NS-398 had no effect at concentrations more than a thousand-fold higher than
their IC50 values. The effects were independent of the presence of prostaglandin
E2 in the medium. Salicylates suppressed activation of the nuclear transcription
factor kappaB, which regulates dendritic cell differentiation, but their effects
on mature dendritic cells were negligible. Hence, aspirin inhibits dendritic cell
function by inhibiting their terminal differentiation at concentrations achieved
in the blood of patients chronically treated with high-dose aspirin.
PMID- 11012754
TI - Calcitonin gene-related peptide inhibits lipopolysaccharide-induced interleukin
12 release from mouse peritoneal macrophages, mediated by the cAMP pathway.
AB - Previously we showed that calcitonin gene-related peptide (CGRP), a neuropeptide,
inhibited lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF
alpha) production and increased interleukin (IL)-6 release at low concentrations
via activation of the cAMP pathway in mouse peritoneal macrophages (Mphi). In
this study we examined whether CGRP could modulate IL-12 release from mouse
peritoneal Mphi, and if so, what signal transduction pathway was involved. Mphi
were obtained from the peritoneal exudate of male BALB/c mice. The cells were
plated on culture dishes at a density of 5 x 105 cells per well and allowed to
adhere for 2 hr. After incubation for 24 hr, the Mphi were cultured with 0.1
microg/ml of LPS, alone or together with CGRP (1-1000 nM) for 24 hr. The amount
of IL-12 in the cell medium was measured by enzyme-linked immunosorbent assay
(ELISA). The results showed that CGRP attenuated LPS-induced IL-12 release in a
concentration-dependent manner. Production of IL-12 was decreased from 95.9+/-4.6
to 73.4+/-5.7 pg/ml by 100 nM CGRP. The two cAMP phosphodiesterase (PDE)
inhibitors, 3-isobutyl-1-methyl-xanthine (IBMX) and rolipram, significantly
potentiated the CGRP response, and the level of IL-12 was further decreased by
28% and 47%, respectively. However, CGRP had no effect on IL-12 production from
unstimulated Mphi. The LPS-induced IL-12 release from Mphi could also be reduced
by forskolin, an activator of adenylate cyclase, and 8-Br-cAMP, an analogue of
cAMP. Using the reverse transcription-polymerase chain reaction (RT-PCR), we
found that CGRP also decreased the LPS-induced IL-12 p40 mRNA levels.
Furthermore, pretreatment with H89 (0.1 microM or 1 microM), an inhibitor of cAMP
dependent protein kinase, diminished CGRP effects, IL-12 production and gene
expression. These data suggest that LPS-induced IL-12 release and gene expression
were attenuated by CGRP via an activated cAMP-protein kinase A (PKA) pathway in
mouse peritoneal Mphi.
PMID- 11012756
TI - Analysis of the mechanism for extracellular processing in the presentation of
human immunodeficiency virus-1 envelope protein-derived peptide to epitope
specific cytotoxic T lymphocytes.
AB - An immunodominant epitope of human immunodeficiency virus-1 (HIV-1) gp160
recognized by Dd class I major histocompatibility complex (MHC) molecule
restricted, CD8+ cytotoxic T lymphocytes (CTL) was originally identified as a
peptide composed of 15 amino acids (P18IIIB: RIQRGPGRAFVTIGK). However, further
study has indicated that a 10-mer peptide, I-10 (RGPGRAFVTI), within P18IIIB is
the minimal-sized epitope and the trimming step(s) of two carboxyl terminal amino
acids (GK) is essential to produce I-10 from P18IIIB. In the processing,
angiotensin-1-converting enzyme (ACE), found in sera, plays a central role in
generating I-10. Target cells could be sensitized with I-10 under conditions
where ACE activity in the sera was abrogated. In contrast, in the case of
P18IIIB, requiring further processing to delete the C-terminus of two amino acids
in order to act, sensitization of target cells was completely abrogated under the
conditions. Pretreatment of target cells with brefeldin A (BFA), preventing the
presentation of endogenous antigens from the class I MHC molecule pathway, did
not inhibit the presentation of P18IIIB. Moreover, glutaraldehyde-fixed cells,
which can not process native protein, though they could present the exogenously
added peptides, were also sensitized by P18IIIB. These results clearly
demonstrate that the fine processing to produce I-10 occurred in the
extracellular milieu. Furthermore, our result suggests that the longer P18IIIB
can bind to the class I molecules on the cell surface, and then be trimmed by ACE
while it is bound. The mechanisms behind the extracellular processing outlined in
this paper will offer important information for designing peptide-based vaccines
to elicit MHC molecule-restricted effectors.
PMID- 11012755
TI - In vitro treatment of human transforming growth factor-beta1-treated monocyte
derived dendritic cells with haptens can induce the phenotypic and functional
changes similar to epidermal Langerhans cells in the initiation phase of allergic
contact sensitivity reaction.
AB - Human monocyte-derived dendritic cells (MoDCs) obtained from peripheral blood
monocytes (PBMC) cultured with granulocyte-macrophage colony-stimulating factor
(GM-CSF) and interleukin-4 (IL-4) can be activated in vitro by a variety of
simple chemicals such as haptens and several metals. Recently, it has been
demonstrated that transforming growth factor-beta1 (TGF-beta1) can induce further
differentiation of MoDCs to the cells that share some characteristics with
epidermal Langerhans cells, i.e. they contain Birbeck granules and express E
cadherin. In this study, using such TGF-beta1-treated dendritic cells (TGF-beta1+
DCs), we examined the in vitro effects of representative haptens, i.e. NiCl2 and
dinitrochlorobenzene (DNCB), on their phenotypic and functional characteristics,
comparing with those reported in vivo in epidermal Langerhans cells during the
sensitization phase of a contact sensitivity reaction. Treatment of TGF-beta1+
DCs with NiCl2 increased their expression of the molecules related to antigen
presentation such as CD86, major histocompatibility complex class I and class II,
and CD83, although weakly, in addition to that of those essential for their
migration to the regional lymph nodes, such as CD49e, CD44 and its variant 6,
while it down-regulated the expression of the molecules required for homing to
the skin and staying in the epidermis, such as cutaneous leucocyte antigen (CLA)
and E-cadherin. It also increased the production of tumour necrosis factor-alpha,
but not that of IL-1beta or IL-12. DNCB also increased their CD86 expression and
down-regulated E-cadherin and CLA, but did not affect other phenotypic changes
that were observed in TGF-beta1+ DCs treated with NiCl2. TGF-beta1+ DCs treated
with either NiCl2 or DNCB increased their allogeneic T-cell stimulatory function.
In addition, reverse transcribed polymerase chain reaction revealed augmented
expression of chemokine receptor 7 mRNA by TGF-beta1+ DCs when treated with
either NiCl2 or DNCB. Moreover, consistent with this data, TGF-beta1+ DCs treated
with these chemicals chemotactically responded to macrophage inflammatory protein
3beta. These data suggest the possibility that TGF-beta1+ DCs present a good in
vitro model to study the biology of epidermal Langerhans cells.
PMID- 11012757
TI - The contribution of both oxygen and nitrogen intermediates to the intracellular
killing mechanisms of C1q-opsonized Listeria monocytogenes by the macrophage-like
IC-21 cell line.
AB - Listeria monocytogenes is a facultative intracellular pathogen which is
internalized by host mammalian cells upon binding to their surface. Further
listerial growth occurs in the cytosol after escape from the phagosomal-endosomal
compartment. We have previously reported that C1q is able to potentiate L.
monocytogenes phagocytosis upon bacterial opsonization by ingestion through C1q
binding structures. In this report, we analysed the post-phagocytic events upon
internalization of C1q-opsonized L. monocytogenes and found an induction of
macrophage (Mphi)-like IC-21 cell bactericidal mechanisms displayed by the
production of oxygen and nitrogen metabolites. Both types of molecules are
effective in L. monocytogenes killing. Further analysis of the cellular responses
promoted by interaction of C1q with its surface binding structures, leads us to
consider C1q as a collaborative molecule involved in Mphi activation. Upon
interaction with surface binding structures, C1q was able to trigger and/or
amplify the production of reactive oxygen and nitrogen intermediates induced by
stimuli such as interferon-gamma and L. monocytogenes phagocytosis.
PMID- 11012758
TI - Reversal of ultraviolet radiation-induced immune suppression by recombinant
interleukin-12: suppression of cytokine production.
AB - Exposure to ultraviolet (UV) radiation, a complete carcinogen, suppresses the
immune response. Data from a number of laboratories have indicated that one
consequence of UV exposure is suppressed T helper type 1 (Th1) cell function with
normal Th2 cell activation, resulting in a shift to a Th2-like phenotype. The
reversal of UV-induced immune suppression and tolerance induction by recombinant
interleukin-12 (rIL-12) supports this observation. The focus of this study was to
determine the mechanism(s) by which rIL-12 reverses UV-induced immune
suppression. Two possibilities were considered: up-regulation of interferon-gamma
(IFN-gamma) secretion by rIL-12 and suppression of UV-induced cytokine secretion
by rIL-12. To our surprise we found that the ability of rIL-12 to overcome UV
induced immune suppression was independent of its ability to up-regulate IFN
gamma secretion. Rather, rIL-12 suppressed the production of cytokines that are
known to be important in UV-induced immune suppression. Injecting UV-irradiated
mice with rIL-12, or adding rIL-12 to UV-irradiated keratinocyte cultures
suppressed IL-10 secretion, in part by affecting the transcription of the IL-10
gene. Furthermore, we found that rIL-12 suppressed UV-induced tumour necrosis
factor-alpha (TNF-alpha) production. Because IL-10 is involved in the UV-induced
suppression of delayed-type hypersensitivity and TNF-alpha in the UV-induced
suppression of contact allergy, these findings provide a mechanism to explain how
rIL-12 overcomes UV-induced immune suppression in these related but different
immune reactions. In addition, they suggest a novel mechanism by which rIL-12
alters immune reactivity, direct suppression of cytokine secretion induced by UV
radiation.
PMID- 11012759
TI - Alteration in the responsiveness to tumour necrosis factor-alpha is crucial for
maximal expression of monocyte chemoattractant protein-1 in human neutrophils.
AB - We previously reported delayed expression of monocyte chemoattractant protein-1
(MCP-1) in human neutrophils cultured with a cytokine-rich crude supernatant of
phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PHA-sup).
Tumour necrosis factor-alpha (TNF-alpha) contained in the PHA-sup played a key
role in this event, but there appeared to be another factor(s) in the same
supernatant that co-operated with TNF-alpha for maximal MCP-1 expression. In the
present study, we reduced TNF-alpha concentrations in the PHA-sup to minimal
levels using anti-TNF-alpha affinity columns (TNF-depleted-sup) and investigated
the co-operation between TNF-alpha and TNF-depleted-sup. Nine hours of
preincubation with TNF-depleted-sup altered the responsiveness of neutrophils to
TNF-alpha and enabled TNF-alpha to increase the level of MCP-1 expression to a
maximal level within 4 hr. The priming effect was not due to the increased
expression of cell-surface TNF receptors. However, the activation of primed cells
by TNF-alpha was clearly through TNF receptor-p55. Finally, the activity in the
TNF-depleted-sup that co-operated with TNF-alpha was eluted at 60 000 MW on high
performance liquid chromatography-gel filtration. Thus, delayed neutrophil
expression of MCP-1 is regulated by a cytokine-dependent mechanism that induces
neutrophils to enter a 'mature' stage.
PMID- 11012760
TI - Structure/function studies of human decay-accelerating factor.
AB - The decay-accelerating factor (DAF) contains four complement control protein
repeats (CCPs) with a single N-linked glycan positioned between CCPs 1 and 2. In
previous studies we found that the classical pathway regulatory activity of DAF
resides in CCPs 2 and 3 while its alternative pathway regulatory activity resides
in CCPs 2, 3 and 4. Molecular modelling of the protein predicted that a
positively charged surface area on CCPs 2 and 3 (including KKK125-127) and nearby
exposed hydrophobic residues (L147F148) on CCP3 may function as ligand-binding
sites. To assess the roles of the N-linked glycan and the above two sets of amino
acids in the function of DAF, we mutated N61 to Q, KKK125-127 to TTT and L147F148
to SS. Following expression of the mutated cDNAs in Chinese hamster ovary cells,
the glycosylphosphatidylinositol (GPI)-anchored mutant proteins were affinity
purified and their functions were assessed. In initial assays, the proteins were
incorporated into sheep and rabbit erythrocytes and the effects of the mutations
on regulation of classical and alternative C3 convertase activity were quantified
by measuring C3b deposition. Since DAF also functions on C5 convertases,
comparative haemolytic assays of cells bearing each mutant protein were
performed. Finally, to establish if spatial orientation between DAF and the
convertases on the cell surface played any role in the observed effects, fluid
phase C3a generation assays were performed. All three assays gave equivalent
results and showed that the N-linked glycan of DAF is not involved in its
regulatory function; that L147F148 in a hydrophobic area of CCP3 is essential in
both classical and alternative pathway C3 convertase regulation; and that KKK125
127 in the positively charged pocket between CCPs 2 and 3 is necessary for the
regulatory activity of DAF on the alternative pathway C3 convertase but plays a
lesser role in its activity on the classical pathway enzyme.
PMID- 11012761
TI - Immunoglobulin E antibodies of atopic individuals exhibit a broad usage of VH
gene families.
AB - The term 'atopy' describes the genetically determined tendency to mount
immunoglobulin E (IgE) antibody responses against per se harmless antigens
(allergens). In this study we investigated the usage of VH families in the
formation of IgE antibodies in 10 patients suffering from mucosal and/or skin
manifestations of atopy. IgE antibody reactivities to exogenous allergen sources
as well as to autoallergens were determined and, by immunoabsorption, it was
demonstrated that allergen-specific IgE accounted for most of the total serum IgE
levels in these patients. Using primers with specificity for the VH1-6 gene
families and a primer specific for the first constant region of human IgE, cDNAs
coding for IgE heavy chain fragments were amplified using the reverse
transcription-polymerase chain reaction (RT-PCR) from peripheral blood
lymphocytes of the 10 atopic individuals. Hybridization of the heavy chain
encoding cDNAs with an IgE-specific internal oligonucleotide probe revealed a
broad usage of all VH-gene families in the atopic individuals. The spectrum of VH
families used in a given atopic individual was neither associated with the type
or severity of clinical symptoms nor with the number of allergens recognized. The
fact that allergen-specific IgE antibodies in atopic individuals originate from a
broad variety of B cells thus reflects the activation of multiple B-cell clones
during allergen sensitization. This finding should be borne in mind if
therapeutic strategies for Type I allergy are considered that aim at a clonal
elimination of allergen-specific B cells.
PMID- 11012762
TI - Feline leukaemia virus: protective immunity is mediated by virus-specific
cytotoxic T lymphocytes.
AB - Feline leukaemia virus (FeLV) nucleic acid vaccination of domestic cats affords
protection against viraemia and the development of latency without inducing
antiviral antibodies.1 To determine the contribution of cell-mediated immunity to
the control of virus replication and clearance from the host, FeLV-specific
cytotoxic T lymphocyte (CTL) responses were compared in vaccine-protected,
transiently viraemic, and persistently viraemic cats. Vaccinal immunity was
associated with the detection of higher levels of virus-specific effector CTL in
the peripheral blood and lymphoid organs to FeLV Gag/Pro and Env antigens than
those observed in unvaccinated control, persistently viraemic cats (P<0.001).
Likewise, higher levels of virus-specific CTLs were also observed in transiently
viraemic cats which recovered following exposure to FeLV. In cats that controlled
their infection, recognition of Gag/Pro antigens was significantly higher than
the recognition of Env antigens. This is the first report highlighting the very
significant role that virus-specific CTL have in determining the outcome of FeLV
infection in either vaccinated cats or cats recovering naturally from FeLV
exposure.
PMID- 11012763
TI - Immunity to vaginal herpes simplex virus-2 infection in B-cell knockout mice.
AB - We investigated the involvement of antibody in protection against vaginal herpes
simplex virus type-2 (HSV-2) infection by comparing intact and B-cell knockout
(KO) mice. Vaginal immunization of intact mice with attenuated HSV-2 markedly
reduced an HSV-2 challenge infection in the vagina. In contrast, immunization of
B-cell KO mice produced less immunity against the challenge infection and that
immunity occurred in a different pattern. At 20 hr after challenge,
immunostaining of virus proteins in the vaginal epithelium and shed virus protein
titres in the vaginal secretions were not significantly different between
immunized and non-immunized B-cell KO mice and were much greater than in
immunized intact mice. At 48 hr after challenge, the vaginal infection in
immunized B-cell KO mice was markedly less than at 20 hr but remained
approximately sevenfold higher than in intact mice. This pattern of challenge
infection in the vagina indicates that B cells, and probably the antibody derived
from them, provided significant protection against reinfection in intact mice,
especially during the first 20 hr after challenge, while other effector
mechanisms became important between 20 and 48 hr after challenge. To determine
whether T-cell immunity in immunized B-cell KO mice was equal to that in intact
mice, we assessed interferon-gamma (IFN-gamma) secretion by memory T cells in
vivo in the vagina at 20 hr after challenge. We found no significant differences
in the up-regulation of major histocompatibility complex (MHC) class II antigens
in the epithelium, up-regulation of vascular cell adhesion molecule-1 (VCAM-1) in
vascular endothelium, or recruitment of T cells to the mucosa, indicating that
the memory T-cell response to virus challenge was the same in intact and B-cell
KO mice.
PMID- 11012764
TI - T lymphocytes from granulocyte colony-stimulating factor-/- mice produce large
quantities of interferon-gamma in a chronic infection model.
AB - Little is known about the role of granulocyte colony-stimulating factor (G-CSF)
in the response to chronic bacterial infections. To address this we infected G
CSF knock out (G-CSF-/-) mice with Mycobacterium avium. Infection was not
exacerbated in G-CSF-/- mice despite a deficiency in the total bone marrow cells,
colony-forming haemopoietic cells, granulocytes and monocyte precursors in the
bone marrow. Peritoneal cells from G-CSF-/- produced less nitric oxide (NO) upon
culture in vitro with antigen than did wild-type (WT) cells. Unexpectedly, T
cells from infected G-CSF-/- mice were able to produce significantly more
interferon-gamma (IFN-gamma) than the wild type (WT) controls. T cells from G-CSF
/- mice still produced more IFN-gamma even when in vitro NO production was
inhibited, while enzyme-linked immunospot assay (ELISPOT) assays showed more IFN
gamma-producing cells in the G-CSF-/- mice. This was confirmed by intracellular
cytokine staining (ICCS), which showed that there were more IFN-gamma producing T
cells in vivo in the G-CSF-/- than the WT controls following M. avium infection.
It is possible that a deficit of NO in vivo allows T cells to develop a higher
IFN-gamma-producing phenotype. Thus we show a novel relationship between G-CSF
and IFN-gamma production by T cells revealed in this chronic bacterial infection
model.
PMID- 11012765
TI - Interleukin-8 fails to induce human immunodeficiency virus-1 expression in
chronically infected promonocytic U1 cells but differentially modulates induction
by proinflammatory cytokines.
AB - This study addresses the role of interleukin (IL)-8, a CXC-chemokine, the level
of which is reported to be raised in the peripheral circulation of human
immunodeficiency virus-1 (HIV-1)-infected individuals, during the induction of
HIV-1 expression from latency and during cytokine-mediated HIV-1 up-regulation.
IL-8 at the higher concentrations tested (> or = 100 ng/ml) was unable to induce
HIV-1 expression in the chronically infected promonocytic U1 cell line, as
measured by p24 antigen enzyme-linked immunosorbent assay (ELISA), whereas at
lower concentrations of 1 and 10 ng/ml, constitutive HIV-1 expression was only
marginally reduced. HIV-1 replication in acutely infected U937 cells was also
significantly reduced by IL-8. The potent up-regulation of HIV-1 expression in U1
cells by tumour necrosis factor-alpha (TNF-alpha) remained unaffected by the
addition of IL-8. HIV-1 induction by IL-1beta, IL-6 and TNF-beta, cytokines
grouped here as intermediate HIV-1 inducers, was suppressed by IL-8 at
concentrations of 1 and 10 ng/ml. However, IL-8 at 100 ng/ml did not
significantly alter the effect of IL-1beta, synergized with IL-6 in enhancing,
and marginally suppressed TNF-beta-induced HIV-1 expression. IL-8 suppressed
granulocyte-macrophage colony-stimulating factor (GM-CSF) and enhanced interferon
gamma (IFN-gamma)-induced HIV-1 expression in a dose-dependent manner.
Pretreatment of U1 cells with IL-8 did not alter the IL-8-mediated effects on
cytokine-induced HIV-1 expression, suggesting that this chemokine exerts its
effect at the time of HIV-1 induction or at a postinduction stage. Furthermore,
IL-8 was itself induced by cytokines that up-regulate HIV-1 expression in U1
cells and the levels produced correlated directly with the levels of p24 antigen
produced, suggesting common pathways for cytokine induction of both HIV-1 and IL
8. These results show that IL-8, typically a non-inducer, can differentially
modulate HIV-1 expression in U1 cells and that this is dependent on the inducing
cytokine and on the concentration of IL-8.
PMID- 11012766
TI - The Rubino test for leprosy is a beta2-glycoprotein 1-dependent antiphospholipid
reaction.
AB - We describe the isolation and identification of three components required for the
Rubino reaction (RR), which is the rapid sedimentation of formalinized sheep red
blood cells (SRBC) initiated by serum from leprosy patients with defective
Mycobacterium leprae-specific cell immunity. The Rubino reaction factor (RRF)
required for this phenomenon, previously identified as an immunoglobulin M (IgM),
was purified from leprosy patient serum by adsorption to formalinized SRBC.
Purified RRF IgM, when added to formalinized SRBC, did not produce a positive RR.
However, when the contact was carried out in the presence of normal human serum
(NHS), cells rapidly sedimented. The purified cofactor from NHS contained two
components of 70 000 and 50 000 molecular weight (MW), as determined by sodium
dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The latter was
recognized by the RRF IgM on immunoblot and its N-terminal sequence indicated
that it was beta2-glycoprotein 1 (beta2-GP1), an anionic phospholipid-binding
protein. Methanol-treated formalinized SRBC did not support the RR. Thin-layer
chromatography of an extract of membranes indicated that the SRBC ligand was a
cell-surface phospholipid. Cardiolipin inhibited the RR. These data demonstrate
that the RR involves a trimolecular interaction in which IgM, beta2-GP1 and an
SRBC phospholipid participate. By analogy with the antiphospholipid antibodies
(anti-PL) that occur in autoimmune processes, serum samples from 29 systemic
lupus erythematosus patients with high levels of anticardiolipin antibodies were
submitted to the RR. A positive RR was obtained for 45% (13 of 29 patients).
These results modify the paradigm of the absolute specificity of the RR for
leprosy and demonstrate that RRF IgM is a beta2-GP1-dependent anti-PL.
PMID- 11012767
TI - Genetically detoxified mutants of heat-labile enterotoxin from Escherichia coli
are effective adjuvants for induction of cytotoxic T-cell responses against HIV-1
gag-p55.
AB - There is an urgent need for prophylactic and therapeutic vaccines against human
immunodeficiency virus (HIV). Mucosal immunization strategies have great
potential to elicit both mucosal and systemic cellular immunity required to
protect against HIV-induced acquired immune deficiency syndrome (AIDS). However,
mucosal immunizations with soluble protein antigens generally require adjuvants.
In this study, we tested two mutants of the heat-labile enterotoxin (LT) from
Escherichia coli, LTK63: with no measurable ADP-ribosyltransferase activity, and
LTR72: with residual ADP-ribosyltransferase activity, as mucosal adjuvants for
induction of cytotoxic T lymphocyte (CTL) responses to coadministered HIV gag p55
protein. We found that intranasal (i.n.) immunizations with HIV gag p55 protein
coadministered with LTK63 or LTR72 induced systemic CTL responses comparable to
that obtained following intramuscular (i. m.) immunizations with the same
adjuvants. Moreover, oral coadministration of LTR72, but not LTK63, resulted in
local as well as systemic p55-specific CTL responses in mesenteric lymph nodes
(MLN) and spleens (SP) of the immunized mice. These data have important
implications for current efforts to develop a safe vaccine against HIV.
PMID- 11012768
TI - Intestinal lymphocyte number, migration and antibody secretion in young and old
rats.
AB - This study demonstrates that the mucosal immune response to cholera toxin (CT) is
compromised in old rats in comparison with young animals. The total number of
immunoglobulin A (IgA)-secreting cells is similar or higher in the intestinal
inductor and effector sites in old animals. However, the number of specifically
induced anti-CT IgA antibody-secreting cells is lower in these tissues in
comparison with those in young animals. The kinetics of this immune response in
the different gut-associated lymphoid tissues studied suggests that the age
associated decline in the number of anti-CT IgA-secreting cells in the intestinal
mucosa reflects impaired IgA immunoblast migration. Our data from lymphocyte
adoptive transfer studies indicate that factors intrinsic to both the donor cells
and the host recipient influence the migration of immunoblasts from the Peyer's
patches to the effector site. For example, donor cells from old donors
transferred to either young or old recipient rats migrate slower than young donor
lymphocytes transferred into old host animals. In vitro studies clearly indicate
that ageing does not impair antibody secretion by intestinal mucosal plasma
cells. Therefore, the age-related decline in the intestinal mucosal immune
response, e.g. diminished specific antibody titres in intestinal lavage, reflects
fewer antibody-secreting cells in the mucosa.
PMID- 11012769
TI - CD28, CTLA-4 and their ligands: who does what and to whom?
PMID- 11012770
TI - Phenotypic analysis of peripheral CD4+ CD8+ T cells in the rat.
AB - Among peripheral T cells, the expression of CD4 and CD8 is almost mutually
exclusive. However, here we show, using flow cytometric analysis, that ex vivo
approximately 6% of rat T cells stained for both CD4 and CD8. These double
positive cells were also detected by confocal microscopy. Only around 50% of
double positive cells expressed the CD8beta chain, the remaining cells expressed
the CD8alpha chain alone. Double positive cells were blast-like with a phenotype,
distinct from that of either CD4 or CD8 single positive cells, suggestive of an
activated state. Previous reports of double positive T cells have also suggested
that coexpression of CD4 and CD8 is linked to the activation state of the cell.
There was an indication that priming animals with a hapten-carrier complex
increased the ratio of CD8alphaalpha : alphabeta expressing double positive T
cells, although we did not detect an increase in the frequency of double positive
T cells following priming. We also show that the frequency of double positive
cells was reduced following thymectomy and with age. In conclusion, these studies
show that peripheral T cells expressing both CD4 and CD8 can be detected in the
rat and that they are phenotypically distinct from CD4 and CD8 single positive T
cells.
PMID- 11012771
TI - Staphylococcal enterotoxin B induces potent cytotoxic activity by intraepithelial
lymphocytes.
AB - In food poisoning, Staphylococcus aureus secretes staphylococcal enterotoxin B
(SEB), a superantigen that causes intense T-cell proliferation and cytotoxicity.
The effects of SEB on lytic activity by human intestinal intraepithelial
lymphocytes (IEL) were investigated. Jejunal IEL, from morbidly obese individuals
undergoing gastric bypass operations, were tested for SEB-induced cytotoxicity
against C1R B-lymphoblastoid cells, HT-29 adenocarcinoma cells, or CD1d
transfected cells using the 51Cr-release assay. Fas and Fas ligand expression
were detected by immunofluorescence and flow cytometry and soluble ligand by
enzyme-linked immunosorbent assay (ELISA). In the presence of SEB, IEL became
potently cytotoxic against C1R cells and interferon-gamma (IFN-gamma)-precultured
HT-29 cells, causing 55+/-10% and 31+/-6% lysis, respectively, greater than that
by phytohaemagglutinin (PHA)-, interleukin-2 (IL-2)-, or anti-T-cell receptor
(TCR)-activated IEL. SEB-stimulated peripheral blood (PB) CD8+ T cells lysed
similar numbers of C1R cells but fewer HT-29 cells (53+/-13% and 8+/-5%,
respectively). IEL killing of C1R cells involved interaction of major
histocompatibility complex (MHC) class II with TCR, CD2 with CD58, and CD11a with
CD54, and was perforin mediated. SEB-induced IEL lysis of HT-29 cells, in
contrast, was caused by an unknown target cell structure, not MHC class II or
CD1d, and resulted from a combination of perforin and Fas-mediated events. The
potent cytotoxic activities of IEL promoted by SEB utilize two different
mechanisms, depending on the surface receptors expressed by the target cells.
PMID- 11012772
TI - HLA-G has a concentration-dependent effect on the generation of an allo-CTL
response.
AB - Human leucocyte antigen (HLA) -G is expressed on trophoblast cells during
pregnancy, suggesting a role in protection of the semiallogeneic fetus. Published
data suggest that HLA-G protects a cell against natural killer cell lysis. It has
been hypothesized that HLA-G may also protect the fetus by preventing allo
cytotoxic T lymphocyte (CTL) responses. To test this hypothesis, we assayed the
effects of various concentrations of purified HLA-G on CTL response in a mixed
lymphocyte culture (MLC) system. We found that concentrations > or =0.1 microg/ml
of HLA-G suppressed the allo-CTL response by 30-100% over the control, but,
paradoxically, concentrations of 0.01-0.05 microg/ml of HLA-G augmented the allo
CTL response by 25-50% over the control. Concentrations < or = 0.001 microg/ml
HLA-G had no effect. Addition of HLA-G to preprimed allo-CTL effector cells did
not affect their killing ability. Allo-CTL suppressive doses of HLA-G induced a T
helper type 2 (Th2) cytokine response, whereas allo-CTL-enhancing doses of HLA-G
induced a Th1-type cytokine response. HLA-G purified from first-trimester
placenta does not affect allo-proliferative responses nor does it alter the
percentage of CD4+ or CD8+ T cells in MLCs. These findings support a potential
role for HLA-G-mediated suppression of allo-CTL formation in normal pregnancies.
In addition, the effects observed at lower concentrations of HLA-G may have
interesting implications for the condition of pre-eclampsia in which
concentrations of this HLA class I molecule are reduced.
PMID- 11012773
TI - CD5-positive and CD5-negative human B cells converge to an indistinguishable
population on signalling through B-cell receptors and CD40.
AB - Whether CD5 on B cells marks a subset functionally distinct from the conventional
CD5 negative (CD5neg) adult population or is more an indicator of activation,
remains contentious. Here we have investigated whether CD5 positive (CD5pos) and
CD5neg B cells can be distinguished in terms of their response to surrogate
signals aimed to model, in vitro, T-cell dependent (TD) and T-independent (TI)
encounters with antigen in vivo: the predominantly CD5pos B-cell population found
in cord blood, CD5 B cells positively selected from tonsils and their CD5neg
counterparts, were compared. Neonatal B cells displayed a near-identical
phenotype to that of adult CD5pos B cells, being characterized by uniform
immunoglobulin M (IgM), immunoglobulin D (IgD), CD23 and CD44 coexpression. When
cultured with anti-IgM maintained at high density on CD32-tranfected mouse L
cells to model TI responses or on CD40 ligand (CD40L)-bearing L cells (with or
without captured anti-IgM) to model TD encounters, DNA synthesis was stimulated
to a similar extent in all three populations. Focusing on CD5 and CD23, we found
that - although the signals delivered promoted distinct profiles of expression -
under each condition of activation, the phenotypes that emerged for adult CD5pos
and CD5neg B cells were remarkably similar. Neonatal B cells displayed a greater
diminution in CD5 expression than adult CD5pos B cells following CD40 signals but
otherwise the two populations again behaved similarly. The inclusion of
interleukin-4 (IL-4) to cultures where cells were costimulated via surface (s)IgM
and CD40 resulted in a complete loss of CD5 expression and a corresponding
hyperexpression of CD23, irrespective of the population studied. The near
identical response of CD5pos and CD5neg B cells to surrogate TD or TI signals in
vitro and their convergence to indistinguishable phenotypes is wholly supportive
of CD5 being a fluctuating marker of activation rather than it delineating
functionally distinct subsets.
PMID- 11012774
TI - Signals sustaining human immunoglobulin V gene hypermutation in isolated germinal
centre B cells.
AB - Affinity maturation of antibody responses depends on somatic hypermutation of the
immunoglobulin V genes. Hypermutation is initiated specifically in proliferating
B cells in lymphoid germinal centres but the signals driving this process remain
unknown. This study identifies signals that promote V gene mutation in human
germinal centre (GC) B cells in vitro. Single GC B cells were cultured by
limiting dilution to allow detection of mutations arising during proliferation in
vitro. Cells were first cultured in the presence of CD32L cell transfectants and
CD40 antibody (the 'CD40 system') supplemented with combinations of cytokines
capable of supporting similar levels of CD40-dependent GC B-cell growth
[interleukin (IL)-10 + IL-1beta + IL-2 and IL-10 + IL-7 + IL-4]. Components of
the 'EL4 system' were then added to drive differentiation, providing sufficient
immunoglobulin mRNA for analysis. Analysis of VH3 genes from cultured cells by
reverse transcription-polymerase chain reaction (RT-PCR)-based single-strand
conformation polymorphism indicated that the combination IL-10 + IL-1beta + IL-2
promoted active V gene mutation whereas IL-10 + IL-7 + IL-4 was ineffective. This
was confirmed by sequencing which also revealed that the de novo generated
mutations were located in framework and complementarity-determining regions and
shared characteristics with those arising in vivo. Somatic mutation in the target
GC B-cell population may therefore be actively cytokine driven and not simply a
consequence of continued proliferation. The experimental approach we describe
should facilitate further studies of the mechanisms underlying V gene
hypermutation.
PMID- 11012776
TI - M-ficolin is expressed on monocytes and is a lectin binding to N-acetyl-D
glucosamine and mediates monocyte adhesion and phagocytosis of Escherichia coli.
AB - Ficolins are a group of multimeric proteins that contain collagen-like and
fibrinogen-like (FBG) sequences. Three types of ficolins have been characterized:
H-, L- and M-ficolins. Both H- and L-ficolins have demonstrated lectin
activities. In the present study, the FBG domain of M-ficolin was expressed and
shown to bind to N-acetyl-D-glucosamine. M-ficolin mRNA was expressed in
monocytes but not in the more differentiated macrophages and dendritic cells. By
flow cytometry, surface biotinylation and immunoprecipitation, we showed that M
ficolin was associated with the surface of promonocytic U937 cells. M-ficolin
transiently expressed in COS-7 cells was also clearly detected on the cell
surface by immunoprecipitation. By flow cytometry, M-ficolin was detected on
peripheral blood monocytes but not on lymphocytes or granulocytes. Immobilized
rabbit anti-M-ficolin F(ab')2 mediated U937 cell adhesion, and the antibody also
inhibited phagocytosis of Escherichia coli K-12 by U937 cells. Therefore, M
ficolin might act as a phagocytic receptor or adaptor on circulating monocytes
for micro-organism recognition and may potentially mediate monocyte adhesion.
PMID- 11012775
TI - Increased immunoglobulin A levels in milk by over-expressing the murine polymeric
immunoglobulin receptor gene in the mammary gland epithelial cells of transgenic
mice.
AB - The polymeric immunoglobulin receptor (pIgR) transports dimeric immunoglobulin A
(dIgA) across the epithelial cell layers into the secretions of various mucosal
and glandular surfaces of mammals. At these mucosal sites, such as the
gastrointestinal tract, respiratory tract, urogenital tract and the mammary
glands, dIgA protects the body against pathogens. The pIgR binds dIgA at the
basolateral side and transports it via the complex mechanism of transcytosis to
the apical side of the epithelial cells lining the mucosa. Here, the
extracellular part of the receptor is cleaved to form the secretory component
(SC), which remains associated to dIgA, thereby protecting it from degradation in
the secretions. One pIgR molecule transports only one dIgA molecule (1 : 1 ratio)
and the pIgR is not recycled after each round of transport. This implies that the
amount of available receptor could be a rate-limiting factor determining both the
rate and amount of IgA transported per cell and therefore determining the total
IgA output into the lumen or, in case of the mammary gland, into the milk. In
order to test this hypothesis, we set up an in vivo model system. We generated
transgenic mice over-expressing the murine pIgR gene under lactogenic control, by
using a milk gene promoter, rather than under immunological control. Mice over
expressing the pIgR protein, in mammary gland epithelial cells, from 60- up to
270-fold above normal pIgR protein levels showed total IgA levels in the milk to
be 1.5-2-fold higher, respectively, compared with the IgA levels in the milk of
non-transgenic mice. This indicates that the amount of pIgR produced is indeed a
limiting factor in the transport of dIgA into the milk under normal non
inflammatory circumstances.
PMID- 11012777
TI - Contrasting effects of myeloid dendritic cells transduced with an adenoviral
vector encoding interleukin-10 on organ allograft and tumour rejection.
AB - Mouse bone marrow-derived myeloid dendritic cells (DC) propagated in granulocyte
macrophage colony-stimulating factor and transforming growth factor-beta1 (TGF
beta1) (so-called 'TGF-beta DC') are phenotypically immature, and prolong
allograft survival. Interleukin-10 (IL-10) has been shown to inhibit the
maturation of DC by down-regulating surface major histocompatibility complex
(MHC) class II, co-stimulatory and adhesion molecule expression. Genetic
engineering of TGF-beta DC to overexpress IL-10 might enhance their tolerogenic
potential. In this study, adenoviral (Ad) vectors encoding the mouse IL-10 gene
were transduced into B10 (H2b) TGF-beta DC. Transduction with Ad-IL-10 at a
multiplicity of infection (MOI) of 50-100 resulted in a modest reduction in the
incidence of DC expressing surface MHC class II, CD40, CD80 and CD86.
Paradoxically, Ad-IL-10 transduction enhanced the allostimulatory activity of DC
in mixed leucocyte reactions and cytotoxic T lymphocyte assays, and increased
their natural killer cell stimulatory activity. Systemic injection of normal C3H
recipients with Ad-IL-10-transduced B10-DC 7 days before organ transplantation,
exacerbated heart graft rejection and augmented circulating anti-donor
alloantibody titres. Contrasting effects were observed in relation to tumour
growth. All mice preimmunized with Ad-IL-10-transduced, tumour antigen (B16F10)
pulsed DC developed palpable tumours, associated with significant inhibition of
splenic anti-tumour cytotoxic T lymphocyte generation. Animals pretreated with
control Ad-LacZ-transduced, B16F10-pulsed DC however, remained tumour free. These
findings are consistent with the multifunctional immunomodulatory properties of
mammalian IL-10.
PMID- 11012778
TI - Major histocompatibility complex class II- fetal skin dendritic cells are potent
accessory cells of polyclonal T-cell responses.
AB - Whereas dendritic cells (DC) and Langerhans cells (LC) isolated from organs of
adult individuals express surface major histocompatibility complex (MHC) class II
antigens, DC lines generated from fetal murine skin, while capable of activating
naive, allogeneic CD8+ T cells in a MHC class I-restricted fashion, do not
exhibit anti-MHC class II surface reactivity and fail to stimulate the
proliferation of naive, allogeneic CD4+ T cells. To test whether the CD45+ MHC
class I+ CD80+ DC line 80/1 expresses incompetent, or fails to transcribe, MHC
class II molecules, we performed biochemical and molecular studies using Western
blot and polymerase chain reaction analysis. We found that 80/1 DC express MHC
class II molecules neither at the protein nor at the transcriptional level.
Ultrastructural examination of these cells revealed the presence of a LC-like
morphology with indented nuclei, active cytoplasm, intermediate filaments and
dendritic processes. In contrast to adult LC, no LC-specific cytoplasmic
organelles (Birbeck granules) were present. Functionally, 80/1 DC in the
presence, but not in the absence, of concanavalin A and anti-T-cell receptor
monoclonal antibodies stimulated a vigorous proliferative response of naive CD4+
and CD8+ T cells. Furthermore, we found that the anti-CD3-induced stimulation of
naive CD4+ and CD8+ T cells was critically dependent on the expression of
FcgammaR on 80/1 DC and that the requirement for co-stimulation depends on the
intensity of T-cell receptor signalling.
PMID- 11012779
TI - Granulocyte-macrophage colony-stimulating factor regulates cytokine production in
cultured macrophages through CD14-dependent and -independent mechanisms.
AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) has multiple effects on
the antigen phenotype and function of macrophages. In this study we investigated
the effect of GM-CSF on cytokine production by macrophages. We found that GM-CSF
may modify the tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)
response to lipopolysaccharide (LPS) through two different mechanisms. Relatively
early in culture, GM-CSF increases the amount of cytokines synthesized by
responding cells; this effect appears to be unrelated to modulation of CD14
expression and LPS-binding capacity. After prolonged incubation, GM-CSF up
regulates both CD14 expression and LPS-binding capacity, and the frequency of
cytokine-producing cells. Release of CD14 in the culture supernatant was
decreased in the presence of GM-CSF, suggesting that a reduced shedding was
responsible for the effect of GM-CSF on CD14 expression. Enhancement of cytokine
production was also observed in GM-CSF-treated macrophages after stimulation by
phorbol 12-myristate 13-acetate (PMA), thus indicating that GM-CSF affects both
CD14-dependent and -independent cytokine production. Finally, GM-CSF did not
modulate the LPS- and PMA-induced production of IL-10 and IL-12. We conclude that
GM-CSF may play a role in manipulating the activation-induced expression of pro
inflammatory cytokines by macrophages. Enhanced production of these cytokines
could play an important role in the pathogenesis of Gram-negative septic shock
syndrome and in defence against infectious agents.
PMID- 11012780
TI - The lipid A region of lipopolysaccharides from Rhizobiaceae activates bone marrow
granulocytes from lipopolysaccharide-hyporesponsive C3H/HeJ and C57BL/10ScCr
mice.
AB - We established in previous studies that the binding of Salmonella
lipopolysaccharide (LPS) to constitutive receptors of low affinity triggers the
expression of the inducible LPS-binding molecule CD14 in bone marrow cells (BMC)
of C3H/HeOU mice, but not in BMC from C3H/HeJ mice. We show in this study that
BMC from C3H/HeJ and C57BL/10ScCr mice do not express CD14 after exposure to LPSs
from Salmonella enterica and Bordetella pertussis, but do express this marker
when treated with several LPSs from Rhizobiaceae, or their lipid A fragments.
This shows that the constitutive LPS receptor in BMC from C3H/HeJ and
C57BL/10ScCr mice is fully able to trigger a complete signalling cascade. Results
of cross-inhibition of the binding of radiolabelled LPS indicated that active
LPSs (from R. species Sin-1 and R. galegae) and inactive LPSs (from S. enterica
and B. pertussis) bind to the same site of the constitutive LPS receptor of
C3H/HeJ cells. Furthermore, binding of R. species Sin-1 LPS, and signalling
induced by this LPS, were both inhibited by pre-exposure of C3H/HeJ cells to B.
pertussis lipid A. This correlation between binding and signalling suggests that
in C3H/HeJ cells, the constitutive receptor, which recognizes a large panel of
LPSs from different origins, appears selectively unable to be activated by some
particular LPSs, such as those of Enterobacteria and Bordetella.
PMID- 11012781
TI - Human endothelial cells are activated by interferon-gamma plus tumour necrosis
factor-alpha to kill intracellular Pseudomonas aeruginosa.
AB - Proinflammatory cytokines have been shown to activate endothelial cells. To
investigate the effect of cytokines on the interaction of human umbilical vein
endothelial cells (HUVEC) with Pseudomonas aeruginosa, cells were treated with
interferon-gamma (IFN-gamma) plus tumour necrosis factor-alpha (TNF-alpha) for 24
hr and exposed to P. aeruginosa suspension for 1 hr. Light microscopy showed that
activated cells internalized significantly more bacteria than control cells. To
ascertain the effect of cytokines on the microbicidal activity of HUVEC, the
concentrations of viable intracellular (IC) bacteria in control and activated
cells were determined, at 1 and 5 hr postinfection, by the gentamicin exclusion
assay. In control cells, no significant decrease in the concentration of bacteria
was detected 5 hr postinfection. In contrast, in activated cells the
concentration of viable bacteria at 5 hr was significantly lower. Concentrations
of superoxide and hydrogen peroxide detected in supernatants of activated cells
were significantly higher than in control cell supernatants. HUVEC anti-P.
aeruginosa activity was insensitive to the antioxidants superoxide dismutase,
dimethylthiourea and allopurinol as well as to the L-arginine analogues
aminoguanidine and NG-monomethyl-L-arginine (L-NMMA), but was significantly
inhibited by catalase. Our results indicate that HUVEC can be activated by IFN
gamma plus TNF-alpha to kill IC P. aeruginosa and suggest a role for reactive
oxygen radicals, notably hydrogen peroxide, in HUVEC antibacterial activity.
PMID- 11012782
TI - Soluble isoforms of CEACAM1 containing the A2 domain: increased serum levels in
patients with obstructive jaundice and differences in 3-fucosyl-N-acetyl
lactosamine moiety.
AB - CEACAM1 (biliary glycoprotein or CD66a) is a member of the carcinoembryonic
antigen (CEA) subgroup of the CEA family. Eleven RNA isoforms derived from the
splicing of a single CEACAM1 gene have been described. Some of the CEACAM1
isoforms have been recognized by the CD66 antibodies in T and B lymphocytes,
natural killer cells, granulocytes and epithelial cells in several human tissues.
Although it is also present in soluble form in bile and serum, and elevated
levels have been found in the serum of patients with liver diseases, it is not
known which isoforms are primarily involved. In order to learn more about the
distribution and properties of particular CEACAM1 isoforms, we have prepared a
monoclonal antibody specific for the A2 domain of CEACAM1, designated TEC-11.
This antibody does not cross-react with other members of the CEA family.
Immunoblotting analysis revealed that the TEC-11 epitope was present in all cell
types expressing CEACAM1 containing the A2 domain [CEACAM1(A2)], including
granulocytes (160 000 MW isoform) and sperm cells (140 000 MW isoform). A 115 000
MW isoform of CEACAM1(A2) was present in human serum, bile, saliva and seminal
fluid. Human bile, saliva and seminal fluid also contained the 160 000 MW
CEACAM1(A2) isoform. Significantly higher serum levels of the 115 000 MW
CEACAM1(A2) isoform were detected in patients with obstructive jaundice. The 160
000 MW isoform of CEACAM1(A2) in bile, but not a 115 000 MW isoform in serum and
bile, carried the 3-fucosyl-N-acetyl-lactosamine moiety. The combined data
indicate that various isoforms of CEACAM1(A2) are present in different body
fluids where they could take part in different CEACAM1-mediated functions.
PMID- 11012783
TI - Specificity of a new lipid mediator produced by testicular and peritoneal
macrophages on steroidogenesis.
AB - Macrophage-derived factor (MDF) is a lipophilic factor produced by rat testicular
and peritoneal macrophages that maximally stimulates testosterone production by
rat Leydig cells through a steroidogenic acute regulatory protein independent
mechanism. The purpose of the present study was to determine whether MDF is also
produced by human macrophages, and/or if it acts on human steroidogenic cells. We
also studied the tissue-specific functions of MDF by determining if it also acts
on steroidogenic cells of the ovary and adrenal glands and, if so, does it
require new protein synthesis. It was found that MDF was produced by human
peritoneal macrophages, and was capable of stimulating human steroidogenic cells.
In terms of tissue specificity, it was found that primary cultures of rat
adrenocortical cells respond to MDF with increased secretion of aldosterone and
corticosterone, as did rat granulosa cells by producing progesterone. MDF acted
in the presence of cycloheximide, indicating that it does not require new protein
synthesis. These results indicate that MDF may have significant therapeutic
potential and provide a basis for future studies concerning its physiological
role in humans. These results further suggest that MDF is not only involved in
paracrine regulation of Leydig cells, but also has the potential for the local
regulation of steroidogenesis in both granulosa and adrenal cortical cells.
PMID- 11012784
TI - Marmoset spermatogenesis: organizational similarities to the human.
AB - The common marmoset (Callithrix jacchus), a small New World primate of high
fecundity, is widely used in reproductive research. The aim of the present study
was to determine the organization of the germ cells within the seminiferous
epithelium, the duration of the spermatogenic cycle and the number of
spermatogonial mitoses. Antibodies to cAMP response element modulator (CREM) and
proliferating nuclear cell antigen (PCNA) and a cRNA directed against protamine
P2 and morphological criteria were used to discriminate between stages of the
spermatogenic cycle. Plastic sections were used to document the cell associations
present in each of the nine stages of spermatogenesis. Up to five such stages
could be observed within individual cross-sections of seminiferous tubules. Based
on the pattern of incorporation of bromodeoxyuridine the length of the
spermatogenic cycle was estimated to be 10 days and the duration of
spermatogenesis to be 37 days. Four mitotic divisions were noted in
spermatogonia. It is concluded that the organization of spermatogenesis in the
marmoset has similarities to the human ('helical') and this makes the marmoset a
suitable model for studies relevant to human testicular function.
PMID- 11012785
TI - Immunohistochemical localization of V-ATPases in rat spermatids.
AB - The sperm acrosome exhibits a low pH. However, the mechanism of acidification in
the acrosome remains unclear. Vacuolar-type proton ATPase (V-ATPase) has been
shown to play a principle role in generating and maintaining the acidity of
organelles such as lysosomes and endosomes. In this study, we examined whether V
ATPase is localized in the acrosome membranes using immunohistochemical
techniques. Sections of rat testis were immunostained using antibodies against V
ATPase. Under light microscopic observation, the perinuclear region in spermatids
at an early stage of development was heavily immunostained. At the electron
microscopic level, gold particles showing the presence of V-ATPase were localized
to the acrosome membranes in the developing spermatids. V-ATPase was also
localized to the membrane of vesicles locating between the trans-Golgi area and
the acrosome. These observations suggest that V-ATPase may play a role in
acrosome acidification.
PMID- 11012786
TI - In vitro inhibition of rat cauda epididymal sperm glycolytic enzymes by
ornidazole, alpha-chlorohydrin and 1-chloro-3-hydroxypropanone.
AB - Chlorinated antifertility compounds are known to inhibit glycolysis of
spermatozoa as they reside in the epididymis but new compounds need to be
evaluated that retain antifertility action but do not exhibit side-effects. In
this study, two known antifertility agents and a related compound were compared
for their inhibition of rat sperm metabolism and motility in vitro. The dose
dependent inhibition in vitro of the glycolytic enzymes glyceraldehyde-3
phosphate dehydrogenase (GAPDH) and triosephosphate isomerase (TPI) of distal
cauda epididymal rat spermatozoa by (R)-, (S)- and (R,S)-ornidazole (ORN), (R,S)
alpha-chlorohydrin (ACH) and 1-chloro-3-hydroxypropanone (CHOP) was compared. The
direct inhibition of GAPDH by ORN suggests that it inhibits without prior
conversion outside the cell but inhibition was not stereo-specific. The GAPDH,
but not TPI, activity of spermatozoa incubated with ACH and CHOP was highly
correlated with kinematic parameters of spermatozoa incubated in pyruvate- and
lactate-free medium. ACH only inhibited the activity of intact spermatozoa and
the inhibition was not reversed by washing the particulate sperm fraction after
sonication. High concentrations of ACH (100 mmol/L) killed intact rat spermatozoa
and decreased the extent of GAPDH inhibition. CHOP, unlike ACH, was an effective
inhibitor of both intact and sonicated cells. Pre-CHOP, the dimethylketal
precursor of CHOP, and its other hydrolysis product MeOH, were both ineffective
in vitro. CHOP and related ketals may be more effective inhibitors of sperm
glycolysis than ACH and may prove useful for investigating sperm-specific
glycolytic inhibition, a prerequisite for the development of antiglycolytic, post
testicular acting contraceptives.
PMID- 11012787
TI - Immunocytochemical detection of mitochondrial dihydroorotate dehydrogenase in
human spermatozoa.
AB - In mammalian cells the requirement for pyrimidines is met by uridine phosphate
(UMP) de novo synthesis and, to a greater or lesser extent, by salvage of free
nucleosides. The fourth enzyme of the de novo synthesis, the mitochondrially
bound dihydroorotate dehydrogenase (DHODH) was the focus of the present study.
Rabbit anti-DHODH IgG, which was generated using an immunization protocol with
truncated recombinant human DHODH protein and purified by an immunosorbent
method, was used for immunocytochemical detection and localization of this enzyme
in ejaculated human spermatozoa. The presence of DHODH protein was demonstrated
by Western blotting of solubilized membrane fractions with peroxidase conjugated
anti-rabbit IgG in combination with chemiluminescence detection. Indirect
immunofluorescence microscopy, using Cy3-conjugated anti-rabbit IgG, revealed
specific binding in the midpiece of spermatozoa. As these cells no longer have a
demand for de novo biosynthesis of pyrimidines, we hypothesize that the pathway
could serve a specialized function in nitrogen or zinc metabolism during the
process of spermiogenesis and/or epididymal maturation.
PMID- 11012788
TI - Comparative study of disomy and diploidy rates in spermatozoa of fertile and
infertile men: a donor-adapted protocol for multi-colour fluorescence in situ
hybridization (FISH).
AB - Spermatozoa from seven healthy donors (two of whom had already fathered children)
and five infertile patients taking part in the local programme of
intracytoplasmic sperm-injection (ICSI) were investigated for the disomy rates of
chromosomes 13/21, 18, X and Y as well as for the diploidy rates. Two- and three
colour fluorescence in situ hybridization (FISH) was applied after a donor
adapted decondensation pre-treatment: in a preliminary decondensation series the
optimum fluorescence signals were individually determined by variation of the
concentration of the decondensation reagents and the duration of incubation with
these reagents. Strict scoring criteria were applied. The average disomy rates
ranged from 0.10% (chromosomes 13/21) to 0.44% (disomy XY) in the infertile
donors and from 0.07% (disomy XX) to 0.36% (disomy XY) in the controls. The
average diploidy rates were 0.22% and 0.20% for the infertile donors and the
controls respectively. There was no statistically significant difference between
the two groups with respect to the disomy and diploidy rates. Within the two
groups there were inter-individual differences which were partly statistically
significant, indicating considerable inter-donor variation of the aneuploidy
rates.
PMID- 11012789
TI - Diurnal scrotal skin temperature and semen quality. The Danish First Pregnancy
Planner Study Team.
AB - It is well established that heat is associated with reduced sperm production, but
the role of physiological variation in temperature has never been scrutinized in
humans. We studied diurnal scrotal temperature and markers of male fertility in a
population of couples planning their first pregnancy. Sixty men from a cohort of
couples who were planning their first pregnancy were included and scrotal skin
temperature was monitored during 3 days using a portable data recorder. Working
hours and working postures were recorded daily in a questionnaire. Each man
provided a fresh semen sample and the couples were followed for six menstrual
cycles or until a clinical pregnancy was recognized. The median value of scrotal
skin temperature was 33.3 degrees C in the daytime and 34.8 degrees C at night.
In periods of sedentary work, the median temperature was on average 0.7 degrees C
higher (SE=0.2 degrees C). In addition, scrotal temperature was higher in the
daytime, in summer, and in leisure time compared with working hours. Median sperm
concentration among men with more than 75% of their daytime readings above 35
degrees C was 33.4 x 10(6)/mL, compared with 91.8 x 10(6)/mL for men with less
than half of their readings above 35 degrees C (difference 58.4; 95% CI: 25.9
77.8 x 10(6)/mL). It is concluded that a sedentary position is a significant
source of increased scrotal skin temperature, and even moderate and physiological
elevation in scrotal skin temperature is associated with a substantially reduced
sperm concentration. Sedentary work should be considered as an important
potential confounder for reduced sperm count in epidemiological research.
PMID- 11012791
TI - This month in JAN
PMID- 11012790
TI - Addiction: global problem and global response. Complacency or commitment.
PMID- 11012792
TI - Cognitive therapy supervision as a framework for clinical supervision in nursing:
using structure to guide discovery.
AB - Cognitive therapy supervision as a framework for clinical supervision in nursing:
using structure to guide discovery Cognitive therapy has an undisputed evidence
base upon which its clinical application flourishes. This approach is now a well
recognized and widely adopted method used in the treatment of a diversity of
psychological problems. More recently, prominent innovators of this psychotherapy
have devised a framework to guide the clinical supervision of cognitive
therapists. In keeping with its therapeutic application, the cognitive therapy
framework for supervision is focused, structured, educational and collaborative.
It serves to enhance the therapeutic proficiency of the cognitive therapist. In
contrast, the supervision models reported in the recent nursing literature are
less precise in their mission and when evaluated their contribution to nursing is
shown to be dubious. Following an overview of the supervision models commonly
cited in the nursing literature, a more focused comment on the evaluative
research concerning Proctor's three-function interactive model will be offered.
It is suggested that the unconvincing research findings may be related to the
conceptual muddle surrounding clinical supervision, and the expectation for
clinical supervision to deliver more than an opportunity for the progression of
our therapeutic integrity. From this, a cognitive therapy supervision framework
is described and suggested by the authors as a structure from which supervisors
can guide discovery.
PMID- 11012793
TI - An evaluation of nurse rostering practices in the National Health Service.
AB - An evaluation of nurse rostering practices in the National Health Service The
scheduling of nursing time on hospital wards is critical to the delivery of
patient care, resource utilization and employee satisfaction. Over the past
decade many hospital wards in the United Kingdom (UK) have moved away from the
traditional planning of rosters by a single manager, towards more participative
processes known as self-rostering and team rostering. This paper tests the
hypothesis, developed from the literature, that the three types of rostering
approach may be positioned along a continuum. Self-rostering at one extreme, is
conducive to staff empowerment, motivation and roster effectiveness, whilst
departmental rostering, at the other, leads to perceived autocracy, reduced
empowerment, lower levels of staff motivation and roster effectiveness. Team
rostering is positioned mid-way on this continuum. This paper reports the
findings of an empirical study of nurse rostering practices in the UK National
Health Service (NHS), with a view to developing an understanding of the
implications of implementing these three rostering approaches and testing the
above hypothesis. The survey of rostering practices in 50 NHS wards, and in-depth
case studies of seven wards, revealed that each of the three rostering approaches
has benefits and limitations and a picture emerges quite different from that
implied by the research hypothesis. Whilst the literature suggests that the
choice of rostering approach determines the level of perceived autocracy, staff
motivation and roster effectiveness, it is proposed in this paper that selection
of rostering approach should be contingent upon operational context. The paper
concludes with a framework which stipulates that the choice of rostering approach
for a ward should be determined on the basis of four contingent variables,
namely, ward size, demand variability, demand predictability, and complexity of
skill mix. It is recommended that departmental rostering be applied in large
wards with complex rostering problems, whilst team rostering is more appropriate
for medium sized wards, and self-rostering appropriate for small wards.
PMID- 11012794
TI - Hospital nurses' job satisfaction, individual and organizational characteristics.
AB - Hospital nurses' job satisfaction, individual and organizational characteristics
Using the Ward Organizational Features Scales (WOFS), relationships between
aspects of the organization of acute hospital wards, nurses' personal
characteristics and nurses' job satisfaction are examined among a nationally
representative sample of 834 nurses in England. The analysis contributes to a
growing body of evidence demonstrating the importance of interpersonal
relationships to nurses' job satisfaction. In particular, the positive
contribution of the cohesiveness of ward nursing staff is highlighted, but the
potential for many current NHS staffing strategies and work environments to
undermine the development of cohesive working relationships is also noted. Other
influential factors are nurses' relationships with medical staff, perceptions of
their workload and their evaluation of the appropriateness of the system of
nursing being practised. The importance of measuring nurses' subjective
assessments of their work environment is emphasized. A weak association was found
between grade and job satisfaction. Individual nurse characteristics were found
not to be associated with job satisfaction.
PMID- 11012795
TI - The current scope and future direction of perioperative nursing practice in
Victoria, Australia.
AB - The current scope and future direction of perioperative nursing practice in
Victoria, Australia Unlike some overseas countries, perioperative nursing roles
in Australia are largely undeveloped, and very little research has explored the
opinions of perioperative nurses regarding the development of their specialty.
This study was undertaken to identify the current scope, possible future
directions, and the barriers to developing perioperative nursing practice in the
state of Victoria (Australia). The study design was descriptive and utilized
survey methodology. An instrument was constructed by the researcher for the
specific purposes of the study, and comprised three stages of development:
questionnaire development; validation by a panel of experts; and a pilot study.
The questionnaire was sent randomly to selected perioperative nurses (n=224) and
a response rate of 79% (n=176) was obtained. Data were analysed using the
Statistical Package for the Social Sciences (SPSS). Descriptive statistics were
used to summarize data, and independent sample t-tests, one-way ANOVA and
Wilcoxon signed rank tests were used to test differences between groups. For the
purpose of data reduction factor analysis was undertaken. The findings of the
study indicated that the perioperative nursing model in its espoused form is not
being practised, but a large majority of participants believe that perioperative
nursing practice should not be restricted to the intraoperative phase of the
perioperative model. Expanded rather than extended activities and functions were
perceived as more important for development of the specialty, and perceived
barriers to advanced perioperative nursing practice centred predominantly on the
current application of the perioperative model. Recommendations include
refinement of the perioperative nursing model to reflect changes in the delivery
of healthcare, addressing issues of cost associated with further education, and
undertaking interpretive research to provide more detailed information on the
possible future direction for perioperative nursing.
PMID- 11012796
TI - A comparative study of the financing, provision and quality of care in nursing
homes. The approach of four European countries: Belgium, Denmark, Germany and the
Netherlands.
AB - A comparative study of the financing, provision and quality of care in nursing
homes. The approach of four European countries: Belgium, Denmark, Germany and the
Netherlands As result of an increase in the numbers of frail elderly people, most
European countries are facing problems with the financing and provision of
services by nursing homes. At the same time, the expectations of quality of these
services continue to rise. The main question investigated in this study was that
of how countries approach the problems of financing and service provision by
nursing homes and, at the same time, attempt to increase the quality levels in
these institutions. The study was conducted in Belgium, Denmark, Germany and the
Netherlands. A study was made of the relevant literature and questionnaires were
sent to experts in each country. The four countries are addressing the problems
of financing and sufficient service provision by controlling the use of nursing
home services. In addition, financial problems are approached by extending co
payments, encouraging cheaper forms of care and putting pressure on nursing homes
to operate at lower costs. Problems in the provision of care are addressed by
applying more selective admission criteria and offering alternative forms of care
outside the nursing home. As a result nursing home beds are used for those with
the greatest care-dependency. Nursing home services are adjusted to rising
quality expectations by offering a greater range of provision, decreasing the
number of residents per room, improving comfort and improving the training of
nursing staff. Another way to increase the quality of care is to separate the
housing and service functions. Many nursing homes nowadays collaborate
intensively with other facilities for the elderly to cope with all these problems
and changes. The workload for nursing home staff has increased because of the
increasing care-dependency of residents, the demand for higher quality of
services and the financial problems.
PMID- 11012797
TI - Quality in health care and ethical principles.
AB - Quality in health care and ethical principles The last three decades have seen
rapid changes in the way United States of America (USA) health care has been
delivered, financed and regulated. Four major stakeholders have emerged in the
health care debate: patients, providers, payers and public regulatory agencies.
These groups do not agree on a definition of quality health care. This paper
suggests five ethical principles - autonomy, justice, beneficence, non
maleficence, and prudence - be included in the framework of quality health care.
A framework that outlines possible relationships among these ethical attributes
and four major stakeholders is presented.
PMID- 11012798
TI - Protecting children: intuition and awareness in the work of health visitors.
AB - Protecting children: intuition and awareness in the work of health visitors This
paper is based upon an ethnographic study of a group of health visitors engaged
in child protection work. The purpose of this paper is to explore the meanings
individual health visitors attach to events concerned with identifying children
who may be at risk of harm from child abuse, and also the idiosyncratic nature of
health visiting in this complex but everyday social situation. The paper focuses
on understanding the importance of a particular form of knowledge which the
health visitors referred to as 'intuitive awareness'.
PMID- 11012799
TI - Who cares? Offering emotion work as a 'gift' in the nursing labour process.
AB - Who cares? Offering emotion work as a 'gift' in the nursing labour process The
emotional elements of the nursing labour process are being recognized
increasingly. Many commentators stress that nurses' 'emotional labour' is hard
and productive work and should be valued in the same way as physical or technical
labour. However, the term 'emotional labour' fails to conceptualize the many
occasions when nurses not only work hard on their emotions in order to present
the detached face of a professional carer, but also to offer authentic caring
behaviour to patients in their care. Using qualitative data collected from a
group of gynaecology nurses in an English National Health Service (NHS) Trust
hospital, this paper argues that nursing work is emotionally complex and may be
better understood by utilizing a combination of Hochschild's concepts: emotion
work as a 'gift' in addition to 'emotional labour'. The gynaecology nurses in
this study describe their work as 'emotionful' and therefore it could be said
that this particular group of nurses represent a distinct example. Nevertheless,
though it is impossible to generalize from limited data, the research presented
in this paper does highlight the emotional complexity of the nursing labour
process, expands the current conceptual analysis, and offers a path for future
research. The examination further emphasizes the need to understand and value the
motivations behind nurses' emotion work and their wish to maintain caring as a
central value in professional nursing.
PMID- 11012800
TI - The contexts of adherence for African Americans with high blood pressure.
AB - The contexts of adherence for African Americans with high blood pressure African
American men between the ages of 18 and 49 years have the lowest rates of
awareness, treatment and control of high blood pressure (HBP) of all
age/race/gender groups in the United States. A qualitative study was done to gain
an understanding of urban black males' experiences of living with HBP. In-depth
semi-structured interviews were conducted with 19 black males. The interviews
explored perceptions of health, health problems and priorities, and concerns of
daily living that influenced appointment keeping and medication taking. The
sample was a subset of 309 men participating in a 3-year clinical trial to
improve HBP control in an inner city African-American population. Content
analysis of transcribed interviews identified the following themes and related
concerns: (a) personal contexts: meaning of health, high blood pressure and
treatments; (b) social context: living as a young black male in an urban
environment; and (c) cultural context of relating: patient-provider relationship
can make a difference. Influencing participants' responses were: interpreting
symptoms; adjusting medication taking; protecting personal privacy; allocating
limited resources; dealing with addiction; and feeling cared for by a health care
provider. Adherence appeared to be multifaceted and changing depending upon: the
men's social, economic and personal circumstances; empathetic and non-judgemental
assistance from providers; financial concerns and employment; and drug addiction.
Findings are useful in refining high blood pressure interventions.
PMID- 11012801
TI - Re-thinking stroke rehabilitation: the Corbin and Strauss chronic illness
trajectory framework.
AB - Re-thinking stroke rehabilitation: the Corbin and Strauss chronic illness
trajectory framework The dramatic effects of a stroke can have far-reaching
implications for patients and carers. Effective recovery involves a considerable
array of coping strategies that facilitate and promote engagement in the social
world. Their development is a long-term process that requires considerable
effort, motivation and enterprise on the part of patients and their families.
Traditional approaches to the provision of stroke rehabilitation services,
however, appear to be underpinned by frameworks that are short-term in outlook.
As a consequence, nursing interventions often focus on the progression of the
patient through the care system, rather than on facilitating future recovery.
Much of the work of stroke recovery is consequently done by patients and their
families at home, with little provision of ongoing professional help and advice.
This paper explores the application of the Corbin and Strauss Chronic Illness
Trajectory Framework for stroke. In particular, the major concepts of the
framework are applied to a vignette derived from a longitudinal study of
patients' experiences of recovery. The trajectory framework is shown to be a
useful structure that has the potential to enhance the appropriateness of nursing
interventions for stroke patients. However, the validity of the framework can
only be established through its application and evaluation in clinical practice.
The purpose of this paper is to contribute to a debate that encourages
consideration of the framework's utility for nurses to enhance the stroke
rehabilitation experience.
PMID- 11012802
TI - Pattern recognition as a caring partnership in families with cancer.
AB - Pattern recognition as a caring partnership in families with cancer The purpose
of this study was to address the process of a caring partnership by elaborating
pattern recognition as nursing intervention with families with cancer. It is
based on Newman's theory of health as expanding consciousness within the unitary
transformative paradigm and is an extension of a previous study of Japanese women
with ovarian cancer. A hermeneutic, dialectic method was used to engage 10
Japanese families in which the wife-mothers were hospitalized because of cancer
diagnosis. The family included at least the woman with cancer and her primary
caregiver. Each of four nurse-researchers entered into partnership with a
different family and conducted three interviews with each family. The
participants were asked to describe the meaningful persons and events in their
family history. The family's story was transmuted into a diagram of sequential
patterns of interactional configurations and shared with the family at the second
meeting. Evidence of pattern recognition and insight into the meaning of the
family pattern were identified further in the remaining meetings. The data
revealed five dimensions of a transformative process. Most families found meaning
in their patterns and made a shift from separated individuals within the family
to trustful caring relationships. One-third of them went through this process
within two interviews. The families showed increasing openness, connectedness and
trustfulness in caring relationships. In partnership with the family, each nurse
researcher grasped the pattern of the family as a whole and experienced the
meaning of caring. Pattern recognition as nursing intervention was a meaning
making transforming process in the family-nurse partnership.
PMID- 11012803
TI - Nurses' experiences of being present with a patient receiving a diagnosis of
cancer.
AB - Nurses' experiences of being present with a patient receiving a diagnosis of
cancer This paper reports the findings of a study which describes the experiences
of nurses who were present with a patient when they received a diagnosis of
cancer, cancer recurrence or prognosis of terminal cancer. Semi-structured
interviews were conducted with six nurses who had experience of caring for
patients with cancer in an acute surgical setting. Data were analysed using a
phenomenological descriptive approach. Participants' descriptions revealed the
following seven core themes: 'What if it was me?'; divergent feelings; being
there; becoming closer; method of disclosure; time as an influence and learning
by reflection. Possible implications for nursing practice and education are
discussed and recommendations are made for future research.
PMID- 11012804
TI - The needs of family caregivers of frail elders during the transition from
hospital to home: a Taiwanese sample.
AB - The needs of family caregivers of frail elders during the transition from
hospital to home: a Taiwanese sample This study explored the needs of family
caregivers during the transition from hospital to home. Data from 37 face-to-face
interviews with 16 caregivers before discharge and at 2 weeks and 1 month after
discharge were subjected to constant comparative analysis. Findings revealed
changes in family caregivers' needs during the discharge transition. While
preparing to take caregiving responsibility, caregivers reported a need for
various types of information. After the discharge, but before home caregiving
settled into a pattern, they needed help with caregiving practices. After
reaching a pattern for providing family care, caregivers frequently reported
needs for continuous emotional support. These findings provide a basis for
transitional care services such as discharge planning and home health care
services.
PMID- 11012805
TI - Family and staff perceptions of the role of families in nursing homes.
AB - Family and staff perceptions of the role of families in nursing homes Admission
to a nursing home is generally regarded as the termination of family care and the
commencement of institutional care. Research suggests that following placement
families are often expected to relinquish their dependent older relative to the
bureaucracy of the institution. The aim of this study was to investigate family
and nursing home staff perceptions of the role of families caring for residents
in nursing homes. A convenience sample of 44 family carers and 78 nursing home
staff completed questionnaires, and interviews were conducted with 10 family
carers and 10 nursing home staff. The results suggest that family carers
perceived themselves to have a greater role in caring for relatives than that
perceived by the nursing home staff. Either families overestimated their
involvement, or staff underestimated family involvement in caring for residents
in nursing homes. Families were mostly satisfied with their role and with the
care provided in nursing homes. They perceived nurses as providers of technical
care and they perceived themselves as having an important role in providing
social and emotional care. Families trusted the clinical judgement of the staff
but the staff were reluctant to trust family carers, especially in situations
where care involved an element of risk. Family roles were limited by members' own
ability to care and the dependency of the resident, while professional
responsibility and accountability discouraged nurses from sharing some caring
roles. The results indicate that families in this study were more willing to help
in nursing home care and were perhaps under-valued as a resource within the
nursing home setting.
PMID- 11012806
TI - Psychiatric care as seen by the attempted suicide patient.
AB - Psychiatric care as seen by the attempted suicide patient This study highlights
the experiences of patients during in-patient psychiatric care in Sweden
following a suicide attempt. Eighteen patients were interviewed as close to being
discharged as possible. Each respondent was asked to narrate his/her experiences
of the care received. An interview guide concerned the following areas: admission
to the hospital, feelings and reactions, and positive as well as negative
experiences during the hospital stay. The interviews were transcribed verbatim
and a qualitative content analysis concerning the meanings, intuitions,
consequences and the context of the data was performed. Three central categories
were identified: being a psychiatric patient, patients' perceptions of the
caregivers and the care provided, as well as important aspects of the psychiatric
care received. The importance of being well cared for and receiving understanding
and confirmation was emphasized. Lack of confirmation may have contributed in
some cases to a feeling of being burdensome, demands for discharge or even
another suicide attempt. Verbal contacts with the staff were seen as essential
for the process of healing and for the desire to go on living.
PMID- 11012807
TI - Determinants of absconding by patients on acute psychiatric wards.
AB - Determinants of absconding by patients on acute psychiatric wards Absconding by
patients from acute psychiatric wards is a high risk behaviour and has been
linked to harm to self and others. Previous research on the characteristics of
absconders has been overly reliant on officially generated statistics and small
numbers of variables, limiting the conclusions that may be drawn. This paper
reports on a prospective study of absconders from 12 acute admission wards in
three English National Health Service Trusts over 5 months, compared to a control
group matched for ward. Extensive data on absconder and control characteristics
were collected from case records and from nursing staff. Absconders were
significantly different from controls in many respects. Absconding is linked to
other forms of non-compliant patient behaviour, e.g. medication refusal and
involvement in violent incidents. Significant variations in the rates of
absconding were found between different wards, and between different consultant
psychiatrists. Predictive factors were identified by logistic regression. Study
in the diverse fields of non-compliance should be brought together as these
phenomena are likely to be interrelated. Further investigation is required to
determine exactly what it is that consultant psychiatrists and ward nurses do
that affects absconding rates.
PMID- 11012808
TI - Woodlands therapy: an ethnographic analysis of a small-group therapeutic activity
for people with moderate or severe dementia.
AB - Woodlands therapy: an ethnographic analysis of a small-group therapeutic activity
for people with moderate or severe dementia This paper reports on an analysis of
Woodlands therapy (WT), a sensory-motor therapeutic activity that aims to
encourage interaction with people with moderate or severe dementia. The aims of
the study were to examine: the responses of patients to the sensory experiences
and play-based activities that make up a WT session; the factors that influenced
their responses; and the verbal interventions employed by the staff who
facilitated WT sessions. Methods derived from ethnography were used. The data
comprised videotapes of five WT sessions, notes of other sessions, and
discussions with staff involved with the approach. Thematic groups of patients'
responses were formulated. WT mainly appears to engender the responses of
attention, participation and comment. Factors that influence patients' responses
are discussed. The findings indicate that staff facilitation strategies strongly
influence patients' responses to WT. Verbal interventions made by staff are
grouped in terms of their relative helpfulness for promoting positive responses
to WT. Suggestions for practice are made for professional carers undertaking
sensory-motor therapeutic activities for people with dementia.
PMID- 11012809
TI - Correlates of safer sex communication among college students.
AB - Correlates of safer sex communication among college students The purpose of this
study was to examine factors that are thought to promote communication about
safer sex and HIV among college students in the United States of America and to
determine the extent to which communication about safer sex is important in the
use of condoms. A better understanding of factors associated with safer sex
communication can be helpful in developing HIV and STD prevention programmes for
college students. Following approval from the institutional review boards of the
six participating colleges and universities, researchers collected data from a
random sample of students. The study included participant responses if
participants were 18-25 years of age, single and sexually active. For the sample
of 1349 participants, the mean age was 20.6 years. Sixty-three per cent of the
sample was female, 50.5% white, 42.3% African-American, and the remainder of
other ethnic groups. Over 50% of respondents reported frequent condom use, with
28% noting that they used a condom every time and 30.6% reporting condom use
almost every time they had sex. Only 9.6% indicated that they never used a
condom. The results of hierarchical multiple regression analysis revealed that
the perception of quality of general communication with parents, the perception
of a partner's attitude towards communication, communication self-efficacy, and
communication outcome expectancies, were associated with safer sex communication.
However, the association between safer sex communication and condom use was weak,
suggesting that other factors excluded from this study are important in
determining condom use for this sample of respondents. The findings provide some
implications for HIV interventions. Interventions that enhance self-efficacy and
positive outcome expectancies related to communication about safer sex are likely
to foster discussion with a sexual partner. However, they might not lead to
actual condom use.
PMID- 11012810
TI - Stress, pre-term labour and birth outcomes.
AB - Stress, pre-term labour and birth outcomes Preliminary studies have suggested
that stress may be associated with the onset, treatment and outcomes of pre-term
labour; however, a systematic comparison of the stress of women with and without
pre-term labour has not been reported. Therefore, the purpose of this exploratory
study was to compare the stress (daily hassles and mood states) and birth
outcomes of black and white women who experienced pre-term labour (PTL) during
pregnancy with those who did not. The convenience sample consisted of 35 pregnant
women hospitalized in 1996-1997 for the treatment of PTL (24-35 weeks gestation)
and 35 controls matched on age, race, parity, gestational age and method of
hospital payment. Women in the PTL group had significantly higher tension-anxiety
and depression-dejection on the Profile of Mood States (POMS), lower mean
birthweight and mean gestational age, and a higher percentage of babies born <37
weeks and weighing 2500 g or less. Black women in the PTL group and white women
in the control group had significantly higher scores on the fatigue sub-scale of
the POMS and the work and future security sub-scales of the Daily Hassles Scale.
Women in the PTL group whose babies weighed 2500 g or less had significantly
higher scores on the health, inner concern and financial responsibility sub
scales of the Daily Hassles Scale. The findings from this study indicate the need
for further exploration of the interaction of race and stress in understanding
and preventing PTL and low birthweight and the need to examine the role of social
support in preventing pre-term birth after an episode of PTL.
PMID- 11012811
TI - Primary health care in Saudi Arabia: applying global aspects of health for all,
locally.
AB - Primary health care in Saudi Arabia: applying global aspects of health for all,
locally This paper describes the application of primary health care principles in
the Islamic Kingdom of Saudi Arabia. It arose from a doctoral supervisory
experience on a joint programme for women students, operating between a British
and Saudi Arabian University. The research looked at nutritional advice given by
diploma-level nurses to pregnant women attending primary health care centres in
Saudi Arabia. The supervisor supported research that drew on internationally
recognized trends in nursing research (the reflexive learner) whilst attending to
local requirements and conventions of the culture. The student was encouraged
explicitly to site the research within the framework of Islamic teaching and
Saudi culture. The Qur'an was used as an overarching framework within which the
tenets of primary health care were explored. This was seen to be crucial in
addressing World Health Organisation and the International Council of Nurses'
views on contextualizing nursing for the greatest benefit of the population. This
was of particular relevance in Saudi Arabia where research carried out in the
community by women is novel, and as yet there are no nurse theorists from within
Saudi culture.
PMID- 11012813
TI - Intolerable human suffering and the role of the ancestor: literary criticism as a
means of analysis.
AB - Intolerable human suffering and the role of the ancestor: literary criticism as a
means of analysis This essay explores the experience of intolerable human
suffering in Toni Cade Bambara's novel, The Salt Eaters. The method of analysis
is literary criticism, a technique that shares many of the same goals as other
types of inquiry. It employs close reading to illuminate the novel's meaning(s),
thereby revealing information about the nature of intolerable human suffering.
Morrison's characteristics of black art is the literary and cultural framework
that guides the analysis of Bambara's novel. The paradigm has broad application
for nursing. The purpose of this analysis was to describe the role of the
ancestral system as a predictor of the trajectory of suffering. The results
extend Morrison's paradigm and her notion of ancestor to include traditions and
other non-corporeal factors that are essential for well-being and survival. The
protagonist in Bambara's novel, Velma Henry, is the patient and exemplar who does
not succumb to intolerable suffering because of its cumulative weight, but
because she has lost touch with the traditions of her people, an essential
component of her ancestral system. The ancestral system is a rich and complex
network of individuals, groups, customs and beliefs that are instructive,
protective and benevolent. Ancestors are also timeless and provide wisdom, but
when the ancestral system is weak or absent, the trajectory of suffering is not
favourable. Nurses must learn to recognize intolerable human suffering, to
identify the patient's ancestral system, and to work within that system to keep
suffering patients from harm.
PMID- 11012812
TI - An action research inquiry into a health visitor parenting programme for parents
of pre-school children with behaviour problems.
AB - An action research inquiry into a health visitor parenting programme for parents
of pre-school children with behaviour problems Parent education programmes have
recently been given a high profile in this country, such provision deemed
necessary because of the commonality of children's behaviour problems and because
of their potentially far-reaching effects on the child, the family and society.
This action research study, undertaken in Scotland, aims to explore a health
visitor parenting programme for parents of pre-school children with behaviour
problems. Within this study, children with behaviour problems were identified as
those whose parents perceived them to have such problems, the children eliciting
a wide range of behaviours and to varying degrees. Critical social science is the
chosen methodology, since it allows exploration of how people comprehend their
social reality. Group interactions were recorded on audio-tape and themes
associated with the methodology of enlightenment, empowerment and emancipation
were identified. The results of the study demonstrate how a liberating,
collaborative approach to parental education can empower mothers, by increasing
understanding and raising self-esteem.
PMID- 11012814
TI - On the use of narratives in nursing research.
AB - On the use of narratives in nursing research Narratives have always been a path
to knowledge in nursing care but are a recent element within nursing research.
Therefore, this article deals with the narrative and its use within nursing
research. First, the use of narratives in nursing care and nursing research is
examined. Second, Paul Ricoeur's narrative theory with its dimensions of
interpretation, time, action and ethics is presented as a possible methodological
basis. Third, the use of Ricoeur's narrative theory in nursing research is
examined, showing that, at present, support mainly comes from Ricoeur's text
interpretation theory. Finally, a nursing research approach to the narrative,
based on the life-world, is suggested.
PMID- 11012815
TI - Using web-based discussion as a teaching strategy: bioethics as an exemplar.
AB - Using web-based discussion as a teaching strategy: bioethics as an exemplar
Nurses are required to be competent in the area of bioethics based on several
accreditation standards. Bioethics courses are one strategy to develop such a
competency. Bioethics education itself has various goals including the need to
engage in discussion and the ability to debate diverse issues. Providing an
educational experience that meets both disciplinary and topic needs can be
challenging. On-line conferencing through WebBoard 3.0, a web-based discussion
software program, within a graduate level bioethics course successfully
contributed to meeting these needs. A technical description of the WebBoard is
provided in the following discussion along with a description of the integration
of this device into a bioethics course. The WebBoard conferencing allowed all
students to enter the class discussion and especially facilitated discussion for
reticent speakers and distance learners. Evaluations of the bioethics course from
both the faculty and students' perspectives were generally positive. Most
students found the technique easy to use and liked the asynchronous format that
allowed them to read and contribute at any hour of the day or night. Despite the
labour intensive nature of this experience, the strategy ensured participation by
every student, a major goal of the project. Developing an interdisciplinary
situation would increase the value of such an experience.
PMID- 11012816
TI - Moving on from interpretivism: an argument for constructivist evaluation.
AB - Moving on from interpretivism: an argument for constructivist evaluation This
paper examines the research process in the context of an evaluation of work-based
learning. The findings of the evaluation are used to illustrate issues around
roles and relationships within interpretivist research where a separation is
maintained between the researcher, as investigator, and the participants, as the
subject of their investigation. The discussion focuses on: the threatening nature
of evaluation and the way in which that affects the process of inquiry and
learning; the ways in which people's perceptions of research can act as barriers
to the implementation of change; and the consequences of this role separation for
practice development. In exploring these issues the paper argues for an approach
to evaluation research which (a) emphasizes collaboration, (b) is orientated to
change and (c) treats the evaluation process as a learning opportunity through
which professionals acquire the skills and knowledge to investigate and advance
their own practice.
PMID- 11012817
TI - Korean nurses' adjustment to hospitals in the United States of America.
AB - Korean nurses' adjustment to hospitals in the United States of America Due to
shortage of nurses, more nurses from other countries are employed in health care
settings in the United States of America (USA). Little attention has been paid to
understanding how culturally different international nurses adjust to USA
hospitals. The purpose of this study was to investigate how Korean nurses adjust
to USA hospital settings. Grounded theory method was used for sampling procedure,
data collection and analysis in order to describe Korean nurses' experiences from
their perspective and to develop a substantive theory that explains their process
of adjustment. Data were collected using semi-structured formal interviews with a
purposive sample of 12 Korean nurses. The interviews were audio-taped and
transcribed. Analysis of data, using the constant comparative method, revealed
'adjustment to USA hospitals' as the basic social psychological process. Five
categories composed the process: (1) relieving psychological stress; (2)
overcoming the language barrier; (3) accepting USA nursing practice; (4) adopting
the styles of USA problem-solving strategies; and (5) adopting the styles of USA
interpersonal relationships. These five categories capture the essential aspects
of the adjustment process and each category contains a set of sub-categories that
describe Korean nurses' day-to-day experiences that are critical and also
problematic to their adjustment. The process evolves in two stages. In the
initial stage, the first three of the five categories greatly influenced the
nurses' adjustment. From the perspective of the nurses in the study, the initial
stage lasts about 2 to 3 years. The remaining two categories are principal
components of the later stage. It takes an additional 5 to 10 years to complete
this stage. This model highlights both distress and accomplishments of Korean
nurses during their adjustment to USA hospitals. The results of the study may
help USA nurses gain insight in designing and implementing orientation programmes
to facilitate and support Korean nurses' adjustment to USA hospitals.
PMID- 11012818
TI - An impossible dream? images of nursing held by pre-registration students and
their effect on sustaining motivation to become nurses.
AB - An impossible dream? Images of nursing held by pre-registration students and
their effect on sustaining motivation to become nurses Each year approximately 13
000 people enter higher education programmes leading to nurse registration in
England. Evidence suggests that students enter nursing with strong images about
how they will practice. This paper explores the nature of such images and how
they are used to inform students' approaches to nursing practice. Findings come
from a longitudinal study designed to investigate how students develop their
professional knowledge whilst working in clinical settings. Eight pre
registration degree-course nursing students participated in the study. A multi
method approach to data collection was used over their 4-year programme. One
involved in-depth interviews taking place during each of students' clinical
placements. Data were analysed manually and subjected to a constant comparative
method of analysis. From this material individual case studies of the five
completing students were constructed, with participants checking their own case
study to ensure that it reflected their intended meaning. A second phase followed
where cross-case comparison addressed each of the original research questions.
The question relevant to this paper was: What were students' conceptions of
nursing on entry, and how do these influence their development? Findings indicate
that participating students' preconceptions of nursing had a profound influence
on their decision whether to continue with their course, sometimes despite social
and academic set-backs, or to leave nursing. An important contribution to
realizing their aims was their supernumerary status and effective support from
knowledgeable and experienced practitioners. These findings indicate that with
better understanding of the relationship between this form of personal knowing
and practice, educators would have more information with which to select students
and to design professional curricula.
PMID- 11012819
TI - Social perceptions of cancer and their impacts: implications for nursing practice
arising from the literature.
AB - Social perceptions of cancer and their impacts: implications for nursing practice
arising from the literature At the millennium cancer still holds a special
mystique and is imbued with socio-cultural meanings, which extend far beyond the
rational, scientific and biological facts of the disease. Excessive fear and
dread may cause family and friends to display avoidance or overprotective
behaviours to the ill person, who may subsequently perceive dissatisfaction with
social support. Drawing on a literature review this paper explores the impact of
cancer on social relationships. Interpersonal strain in relationship is often
explained in the stigmatization of the illness and this concept is explored
through contemporary social theorizing. These findings have direct implications
for nursing practice where the goal of care is to enhance the support
relationship.
PMID- 11012820
TI - Towards an aesthetics of nursing.
AB - Towards an aesthetics of nursing This paper re-appraises the work of Barbara
Carper on aesthetics and the art of nursing. It identifies serious flaws in
Carper's original arguments and the way in which she and subsequent authors have
conflated the concepts of art and aesthetics in nursing. The paper explores a
broader approach to aesthetics and proposes a way in which a theoretical approach
to nursing aesthetics could be developed. The paper concludes that nursing is a
fit object of aesthetic appreciation and that aesthetic quality is a necessary
attribute of good nursing practice.
PMID- 11012821
TI - Do parents or surrogates have the right to demand treatment deemed futile? An
analysis of the case of Baby L.
AB - Do parents or surrogates have the right to demand treatment deemed futile? An
analysis of the case of Baby L The purpose of this discussion paper is to address
and analyse the ethical issues arising from the following questions: Do parents
or surrogates of newborn infants have the right to demand treatment deemed
'futile'? Should the religious beliefs of the infant's parents be given special
consideration when deciding on the correct course of action? The case of Baby L,
an infant born with severe disability will be used to aid the analysis. It is
argued that health care providers have no obligation to provide 'futile'
treatment based on the surrogates' right to autonomy, but an obligation may arise
from a duty of benevolence. However, acting from a duty of benevolence can ignore
considerations of justice and fairness and does not always prompt the right
course of action. Any decision regarding treatment options will involve ranking
the beliefs and values of the parents or surrogate against the integrity of the
health care team and the interest of society as a whole. The consequences of
continuing or discontinuing life-sustaining treatment for the infant, the parents
and the health care team will also be considered and examined.
PMID- 11012822
TI - Forthcoming contents of volume 32, number 4, october 2000
PMID- 11012823
TI - Digital imaging in transmission electron microscopy.
AB - The digital revolution currently under way, as evidenced by the rapid development
of the Internet and the world-wide-web technologies, is undoubtedly impacting the
field of transmission electron microscopy (TEM). Digital imaging systems based on
charge-coupled device (CCD) technologies, with pixel array size up to 2 k x 2 k
at the present and increasing, are available for TEM applications and offer many
attractions. Is it time to phase out film cameras on TEMs and close the darkrooms
for good? This paper reviews digital imaging technologies for TEM at different
voltages, and contrasts the performance of digital imaging systems with that of
TEM film. The performance characteristics of CCD-based digital imaging systems,
as well as methods for assessing them, are discussed. Other approaches to digital
imaging are also briefly reviewed.
PMID- 11012824
TI - Two-photon image correlation spectroscopy and image cross-correlation
spectroscopy.
AB - We introduce two-photon image correlation spectroscopy (ICS) using a video rate
capable multiphoton microscope. We demonstrate how video rate two-photon
microscopic imaging and image correlation analysis may be combined to measure
molecular transport properties over ranges typical of biomolecules in membrane
environments. Using two-photon ICS, we measured diffusion coefficients as large
as 10(-8) cm2 s(-1) that matched theoretical predictions for samples of
fluorescent microspheres suspended in aqueous sucrose solutions. We also show the
sensitivity of the method for measuring microscopic flow using analogous test
samples. We demonstrate explicitly the advantages of the image correlation
approach for measurement of correlation functions with high signal-to-noise in
relatively short time periods and discuss situations when these methods represent
improvements over non-imaging fluorescence correlation spectroscopy. We present
the first demonstration of two-photon image cross-correlation spectroscopy where
we simultaneously excite (via two-photon absorption) non-identical fluorophores
with a single pulsed laser. We also demonstrate cellular application of two
photon ICS for measurements of slow diffusion of green fluorescent
protein/adhesion receptor constructs within the basal membrane of live CHO
fibroblast cells.
PMID- 11012825
TI - Stereological estimation of integral mixed curvature with application
AB - This article addresses a bounded system of compact smooth surfaces in three
dimensional space. Recently, an unbiased estimator of the integral mixed
curvature of the given system based on a vertical sampling design has been
proposed. The aims of the present paper are: (i) to show that the proposed
estimator may have an infinite variance; (ii) to suggest a modification that has
better statistical properties; (iii) to extend the point estimator to a function
that monitors the curvature along the gradient microstructures; (iv) to present
an application of the method to real microscopic images.
PMID- 11012826
TI - Testing local dependence of spatial structures on images
AB - Associations between two spatial processes can be due to a real dependence
between the two processes or to the dependence on common underlying variables. We
propose to test the existence of a real dependence by use of local tests, leading
to a global test of real dependence and a map of local interactions. We present
first how classical interaction tests based on random rotations between
completely observed processes such as those developed by Berman (Berman. Appl.
Statist. (1986) 35, 54-62), can be integrated in local analyses. For this
purpose, tests are first performed locally, and the distribution of their p
values is then compared to the corresponding value under the null hypothesis. A
similar approach is proposed to test non-stationarity of a point pattern by using
distance statistics popularized by Diggle (Diggle. Statistical Analysis of
Spatial Point Patterns. (1983) Academic Press, New York). The problem of testing
the interaction between a random field and a censoring area pattern process is
discussed and an approach similar to the preceding ones is then proposed. The
methods are mainly applied to agricultural examples but they can be applied to
any microscopical images for which one wishes to analyse the spatial structure.
PMID- 11012827
TI - Is it reasonable to assume a uniformly distributed cooling-rate along the
microslide of a directional solidification stage?
AB - It is commonly assumed that the cooling-rate along the microslide of a
directional solidification stage is uniformly distributed, an assumption which is
typically applied in low cooling-rates studies. A new directional solidification
stage has recently been presented, which is specified to achieve high cooling
rates of up to 1.8 x 104 degrees C min-1, where cooling-rates are still assumed
to be uniformly distributed. The current study presents a closed-form solution to
the temperature distribution and to the cooling-rate in the microslide. Thermal
analysis shows that the cooling-rate is by no means uniformly distributed and can
vary by several hundred percent along the microslide in some cases. Therefore,
the mathematical solution presented in this study is essential for experimental
planning of high cooling-rate experiments.
PMID- 11012828
TI - Cathodoluminescence microscopy characterization of chrome-free refractories for
copper smelting and converting furnaces
AB - The results of an experimental program assessing the potential of several chrome
free refractory materials as potential replacements for the mag-chrome brick
currently used in copper production furnaces are presented. Several commercial
chrome-free bricks were subjected to the standard dip test in a high-copper
calcium ferrite slag. The mineralogical changes in the bricks resulting from
their interaction with the molten slag are described. The use of optical
cathodoluminescence microscopy as an analytical tool is highlighted, along with
reflected light microscopy and scanning electron microscopy-energy dispersive
spectroscopy. Using the three tools together provides a description of the
experimental results not achievable using one or two alone. The penetration
resistance of the potential replacement refractories is comparable to that of mag
chrome, but the substitution of Fe2+ for Mg2+ in the periclase and spinel
crystalline structures of the replacements reduces their corrosion resistance
compared with mag-chrome, diminishing the likelihood that they will serve as
reliable alternatives.
PMID- 11012829
TI - Electric field depolarization in high aperture focusing with emphasis on annular
apertures
AB - Electromagnetic focusing theory of light predicts that at high apertures field
components arise that are polarized perpendicular to the initial polarization.
Although vectorial depolarization has received considerable attention in focusing
theory, no evidence has been presented as to its relevance in experiments. We
measure the intensity of the perpendicularly orientated field in the focal region
by utilizing monomolecular, fluorescent polydiacetylene layers whose transition
dipoles are orientated in a single direction. For a 1.4 numerical aperture oil
objective lens illuminated with linearly x-polarized light, we find that the
integral of the modulus squared of the y-polarized focal field amounts to 1.5% of
its x-polarized counterpart. In particular, we show here that the depolarization
increases when using annular apertures. Annuli formed by a central obstruction
with a diameter of 89% of that of the entrance pupil raise the integral to 5.5%.
This compares well with the value of 5.8% predicted by electromagnetic focusing
theory; however, the depolarization is also due to imperfections connected with
focusing by refraction. Besides fluorescence microscopy and single molecule
spectroscopy, the measured intensity of the depolarized component in the focal
plane is relevant to all forms of light spectroscopy combining strong focusing
with polarization analysis.
PMID- 11012830
TI - Strategies for the compensation of specimen-induced spherical aberration in
confocal microscopy of skin.
AB - We consider various strategies for confocal imaging of human skin which seek to
reduce the effects of the specimen-induced aberrations. We calculate the
spherical aberration introduced by the stratified structure of skin and show how
the confocal signal is affected when attempting to image at various depths within
the dermis. Using simple methods it is shown how images might be improved by
compensating for the induced aberration. The methods include the use of an iris
to reduce the pupil area, changing the refractive index of the immersion medium
and using a lens with variable coverglass correction.
PMID- 11012831
TI - A two-channel four-dimensional image recording and viewing system with automatic
drift correction.
AB - Four-dimensional image acquisition systems have been described to analyse various
developmental processes, for example, the Caenorhabditis elegans cell lineage. A
practical problem that is often encountered during recordings is mechanical
slippage of the microscope stage, causing the sample to drift out of focus.
Furthermore, with the advent of green fluorescent protein (GFP) as an in vivo
marker, affordable two-channel imaging systems are needed to correlate gene
expression with changes through development. To overcome the mechanical drift a
device-independent, software-only solution for the MacOS was devised that can
compensate for Z-axis drifts in sample position. The software also allows
recording of 4D stacks in two channels. To correct for drift, a small reference
object beside the main object to be recorded is kept in focus using a simple
autofocus principle, and this automatic drift correction allows for effective 4D
recordings. In addition to the Z-axis drives and the shutters of the microscope,
a video camera can be computer controlled to switch between two light levels.
Second channel live GFP recordings are presently limited by the fact that the
high intensity of the blue light heats and kills C. elegans embyros quickly. To
view and annotate the stacks a MacOS viewing application was developed.
PMID- 11012833
TI - Neuroendocrinology briefings 10: biological timekeeping
PMID- 11012832
TI - Neuroendocrinology briefings 10: biological timekeeping.
AB - The existence of biological clocks was once the subject of considerable debate.
However, research has confirmed that a 24 h (circadian) clock in our brain has a
pronounced influence on when we sleep, eat, drink, etc. Disruptions in clock
function compromise normal daily patterns of hormone release, sleep and body
temperature, and can affect mental and physical well-being. The recent
identification of clock genes and the neural pathways to the clock will
facilitate the development of effective strategies to treat disorders of
circadian function.
PMID- 11012834
TI - Ultradian corticosterone rhythm and the propensity to behave aggressively in male
rats.
AB - Ultradian fluctuations in plasma glucocorticoids have been demonstrated in a
variety of species including humans. The significance of such rhythms is poorly
known, although disorganized ultradian glucocorticoid rhythms have been
associated with behavioural disorders. Here we report that ultradian
glucocorticoid rhythms may establish the propensity to behave aggressively in
male rats. Male rats were significantly more aggressive in the increasing phase
of their corticosterone fluctuation when confronting a male intruder than
counterparts in the decreasing phase of their corticosterone fluctuations facing
such opponents. Corticosterone fluctuations were mimicked by a combination of
treatments with the corticosterone synthesis inhibitor metyrapone and
corticosterone. Again, males with increased plasma corticosterone levels were
more aggressive than counterparts with a decreased plasma corticosterone
concentration. These data suggest that the behavioural response to an aggressive
challenge may vary in the same animal across the day due to the pulsating nature
of corticosterone secretion. Aggressive behaviour is also episodic in humans;
moreover, intermittent explosive behaviour is recognized as a psychological
disorder. It can be hypothesized that a temporal coincidence between the
occurrence of a challenge and a surge in plasma corticosterone concentration may
be one of the factors that promote episodic aggressive outbursts.
PMID- 11012835
TI - Basic fibroblast growth factor priming increases the responsiveness of
immortalized hypothalamic luteinizing hormone releasing hormone neurones to
neurotrophic factors.
AB - The participation of growth factors (GFs) in the regulation of luteinizing
hormone releasing hormone (LHRH) neuronal function has recently been proposed,
but little is known about the role played by GFs during early LHRH neurone
differentiation. In the present study, we have used combined biochemical and
morphological approaches to study the ability of a number of GFs normally
expressed during brain development, including basic fibroblast growth factor
(bFGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I
(IGF-I) to induce survival, differentiation, proliferation, and phenotypic
expression of immortalized (GT1-1) LHRH neurones in vitro, at early (3-days in
vitro, 3-DIV) and late (8-DIV) stages of neuronal differentiation. Comparison of
GF-treated vs untreated neurones grown in serum-deprived (SD) medium demonstrated
bFGF to be the most potent, and insulin the least active in promoting neuronal
differentiation. Thus, at both 3-DIV and 8-DIV, but especially at 8-DIV, bFGF
induced the greatest increase in the total length and number of LHRH
processes/cell and in growth cone surface area. bFGF was also the most active at
3-DIV, and IGF-I at 8-DIV, in counteracting SD-induced cell death, whereas EGF
was the most potent in increasing [3H]thymidine incorporation. All GFs studied
decreased the spontaneous release of LHRH from GT1-1 cells when applied at 3-DIV
or 8-DIV, except for insulin which was inactive at both time-points and bFGF
which was inactive at 8-DIV. Pre-treatment of GT1-1 cells with a suboptimal
('priming') dose of bFGF for 12 h followed by application of the different GFs
induced a sharp potentiation of the neurotrophic and proliferative effects of the
latter and particularly of those of IGF-I. Moreover, bFGF priming counteracted
EGF-induced decrease in LHRH release and significantly stimulated LHRH secretion
following IGF-I or insulin application, suggesting that bFGF may sensitize LHRH
neurones to differentiating effects of specific GFs during development.
PMID- 11012836
TI - Hypervascularization in the magnocellular nuclei of the rat hypothalamus:
relationship with the distribution of aquaporin-4 and markers of energy
metabolism.
AB - In the magnocellular nuclei of the hypothalamus, there is a rich vascular network
for which the function remains to be established. In the supraoptic nucleus, the
high vascular density may be one element, which together with the water channel
aquaporin-4 expressed in the astrocytes, is related to a role in osmoreception.
We tested the osmoreception hypothesis by studying the correlation between
vascular and cellular densities in the paraventricular nucleus and the supraoptic
nucleus. Whether aquaporin-4 is likely to contribute to osmoreception was tested
by studying the distribution in the magnocellular nuclei of the hypothalamus. The
high vascular density may also reflect a high metabolic activity due to the
synthesis of vasopressin and oxytocin. This metabolic hypothesis was tested by
studying the regional cytochrome oxidase histochemistry, the local cerebral blood
flow, and the density of glucose transporter type-1 in the supraoptic and
paraventricular nuclei. All the magnocellular nuclei were characterized by an
extended and intense aquaporin-4 labelling and a weak cytochrome oxidase
histochemistry. The highest vascular density was found in the supraoptic nucleus
and the magnocellular regions of the paraventricular nucleus. The local cerebral
blood flow rates were surprisingly low in the paraventricular nucleus and the
supraoptic nucleus in comparison to the cerebral cortex. Furthermore in these
nuclei, the antibody for glucose transporter type-1 revealed two populations of
vessels differing by their labelling intensity. The similarities observed between
the different nuclei suggest that, in the hypothalamus, all magnocellular regions
sense the plasma osmolarity. The low local cerebral blood flow, and the patterns
of glucose transporter type-1 labelling and cytochrome oxidase histochemistry
suggest that the high vascularization of these hypothalamic nuclei is not related
to a high metabolic capacity in basal conditions.
PMID- 11012837
TI - The effects of ionotropic agonists of excitatory amino acids on the release of
arginine vasopressin in rat hypothalamic slices.
AB - The effects of ionotropic excitatory amino acids agonists on the release of
vasopressin from rat hypothalamic slices were studied. Incubation with increasing
doses of NMDA, kainate or AMPA decreased the release of vasopressin in a dose
dependent manner. The values of the IC50 were 1.0, 9.6, or 3.7 x 10-8 M,
respectively. The inhibitory effect of the various excitatory amino acids tested
was blocked by coincubation with their respective antagonists. Vasopressin
secretion was stimulated to 140.3 +/- 7.6% of controls when the slices were
obtained from chronically (7 days) salt-loaded rats. Addition of 1 x 10-7 M NMDA
or 1 x 10-6 M kainate to the incubation medium antagonized the salt loading
induced increase in vasopressin release. Incubation with 1 x 10-4 M tetrodotoxin
did not change basal vasopressin release, but it blocked the decrease in
vasopressin secretion induced by 1 x 10-7 M NMDA or 1 x 10-6 M kainate or 1 x 10
6 M AMPA. Incubation with 1 x 10-5 M phaclophen (a GABAB antagonist) and 1 x 10-5
M bicuculline (a GABAA antagonist) was without effect on basal vasopressin
secretion while it reversed the inhibition of vasopressin release induced by 1 x
10-7 M NMDA. Incubation with 1 x 10-6 M GABA alone decreased vasopressin
secretion to 64.6 +/- 6.9% of control values. The inhibitory effect of GABA did
not change when 1 x 10-7 M NMDA was added to the incubation medium. These
findings demonstrate that ionotropic excitatory amino acids agonists inhibit
vasopressin secretion from hypothalamic slices. They strongly suggest that this
inhibitory effect is mediated through local GABAergic interneurones.
PMID- 11012838
TI - Agouti related protein in the rat adrenal cortex: implications for novel
autocrine mechanisms modulating the actions of pro-opiomelanocortin peptides.
AB - Agouti related protein (AgRP) is a recently discovered melanocortin receptors
(MCR) antagonist implicated in the control of feeding behaviour. Expression of
AgRP has been shown to be localized by in situ hybridization to the arcuate
nucleus and median eminence of the brain, where it acts as an antagonist to the
MC3 and MC4 receptors, while in the periphery the only significant expression was
located in the adrenal medulla. As AgRP is only a weak antagonist of the MC2 and
MC5 receptors, which are expressed principally by adipocytes and in the adrenal
cortex, the question arizes as to the function of peripheral AgRP. In this study,
we investigated the expression of AgRP in the rat adrenal and suggest that it is
expressed in the adrenal cortex and not as previously described in the medulla.
We also show that AgRP mRNA expression is upregulated in the adrenal during
fasting and in the contralateral gland following unilateral adrenalectomy but not
during chronic stress. These results indicate an as yet undefined role for AgRP
in the periphery and are supportive of the suggestion that a further melanocortin
receptor exists.
PMID- 11012839
TI - Pharmacological evidence that prolactin acts from late gestation to promote
maternal behaviour in rabbits.
AB - We investigated the role of prolactin and suckling stimulation in the expression
of maternal behaviour of primiparous rabbits. Bromocriptine (1 mg/kg/day), given
to intact mothers across postpartum days 1-5, decreased serum concentrations of
prolactin to undetectable levels, reduced crouching, and increased time inside
the nest. Failure of maternal nest-building, provoked by bromocriptine injections
from pregnancy day 26 to parturition or to postpartum day 5, correlated with a
stronger reduction in crouching and an increased time inside the nest, measures
of disturbed maternal behaviour, on postpartum days 3 and 5. Preventing suckling
by thelectomy did not prevent prolactin release but reduced crouching incidence
and increased the time spent inside the nest on postpartum days 3 and 5.
Bromocriptine, injected in thelectomized mothers across postpartum days 1-5,
further reduced the incidence of crouching and increased the time spent inside
the nest on postpartum days 3 and 5. We conclude that prolactin acting prepartum
facilitates maternal behaviour initiation in rabbits and, together with pup
stimulation, maintains this behaviour across lactation.
PMID- 11012840
TI - Calcium-independent, tyrosine phosphorylation-dependent effects of serum on the
morphology of cultured neurohypophysial astrocytes.
AB - Activation of adenylate cyclase induces cultured neurohypophysial astrocytes
(pituicytes) to change from a protoplasmic, nonstellate form to a stellate form.
Stellation is inhibited and reversed (destellation) by serum. The objective of
the present studies was to examine the roles of Ca2+ and tyrosine phosphorylation
in mediating these morphological changes. The effects of forskolin (to induce
stellation) and serum (to inhibit and reverse stellation) were not affected by
replacement of Ca2+ with Co2+ in the medium or by treatment of cultures with
thapsigargin. However, genistein, a specific inhibitor of tyrosine kinase(s),
significantly reduced the effect of serum on forskolin-induced stellation. Also,
dephostatin, a specific inhibitor of tyrosine phosphatase, inhibited forskolin
induced stellation. In contrast, genistein did not have a dramatic effect on
serum-induced destellation. The data demonstrate that morphological changes
exhibited by cultured pituicytes are independent of Ca2+ but may be modulated by
the activity of tyrosine kinase(s) and phosphatase(s).
PMID- 11012841
TI - Effect of suckling on NADPH-diaphorase (Nitric oxide synthase, NOS) reactivity
and NOS gene expression in the paraventricular and supraoptic nuclei of lactating
rats.
AB - This study examined the effect of suckling on nicotinamide adenine dinucleotide
phosphate diaphorase (NADPH-d, a histochemical marker for nitric oxide synthase,
NOS) reactivity and neuronal NOS mRNA expression in the paraventricular (PVN) and
supraoptic (SON) nuclei of lactating rats. Freely nursing (non-separated) dams
and those separated from pups for 12 h and then reunited for 0, 15, 30, 60, 90,
120 and 180 min were used for the study. Dams separated from pups and sacrificed
at time zero (without reunion) showed a significant decrease in NADPH-d staining
and NADPH-d positive cells as well as in the NOS mRNA expression in the PVN and
SON compared to that observed in non-separated dams. Reunion with pups and
restoration of suckling significantly increased NADPH-d reactivity after 15, 30,
60 min, but not after 90, 120 and 180 min compared to non-reunited pups-deprived
dams. A pattern of NADPH-d reactivity and neuronal NOS mRNA expression
indistinguishable from that observed during free lactation was reinstated shortly
(15 min) after the restoration of suckling stimulus, suggesting that the NADPH-d
reactivity in lactation depends on the presence of the suckling stimulus. These
results show that suckling stimulus may play a modulatory role in the regulation
of NOS reactivity in the magnocellular neurones of the hypothalamic PVN and SON
during lactation.
PMID- 11012842
TI - The effects of ciliary neurotrophic factor on the hypothalamo-pituitary gonadal
axis in vitro in female rats.
AB - Ciliary neurotrophic factor (CNTF) is a member of the neuropoietic family of
cytokines. CNTF exerts its actions through activation of a receptor complex,
which shows similarity of sequence, second messenger systems and distribution to
the leptin receptor. Leptin has been demonstrated to exert profound effects on
the hypothalamo-pituitary gonadal axis. This study examines the in vitro effects
of CNTF on hypothalamic luteinizing hormone releasing hormone release (LHRH) and
pituitary luteinizing hormone (LH) release compared to those of leptin in the
female. We report that CNTF stimulates LHRH release from medial basal
hypothalamic explants harvested from proestrous female rats and this effect is of
similar magnitude to that seen with leptin. In contrast, CNTF suppresses LHRH
stimulated LH release from dispersed anterior pituitary cells harvested from
proestrous female rats but has no effect on basal LH release. Leptin stimulates
basal LH release but has no effect on LHRH-stimulated LH release. The suppressive
effect of CNTF on LHRH-stimulated LH release has been confirmed in perifused
anterior hemipituitaries. These results suggest a differential effect of CNTF on
the hypothalamo-pituitary gonadal axis and a possible role in the modulation of
pituitary gonadal function.
PMID- 11012844
TI - Selective corticotropin-releasing factor type 1 receptor antagonist blocks
conditioned fear-induced release of noradrenaline in the hypothalamic
paraventricular nucleus of rats.
AB - The effects of conditioned fear on the release of noradrenaline in the
hypothalamic paraventricular nucleus (PVN) and the involvement of corticotropin
releasing factor (CRF) receptor type 1 (CRFR1) in conditioned fear-induced
changes in noradrenaline release were examined by intracerebral microdialysis in
rats. Conditioned fear was produced by placing animals into a box where they had
previously been exposed to a 5-min period of electric footshock, 135 min prior to
the start of experiment. Conditioned fear for 20 min produced a significant
increase in the release of noradrenaline in the PVN. Intraperitoneal
preadministration of a selective nonpeptidic CRFR1 antagonist, CRA1000,
completely blocked the conditioned fear-induced release of noradrenaline. These
results suggest that CRFR1 is involved in the release of noradrenaline in the
hypothalamic PVN induced by conditioned fear.
PMID- 11012843
TI - Blunted pituitary-adrenocortical stress response in adult rats following neonatal
dexamethasone treatment.
AB - Glucocorticoids have a prominent impact on the maturation of the stress-related
neuroendocrine system and on the postnatal establishment of adaptive behaviour.
The present study aimed at investigating the stress responsiveness of the
hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after
neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone.
Newborn male Wistar rats were injected s.c. with 1 microg/g dexamethasone on
postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and
corticosterone concentrations were measured in the resting state and following a
30-min cold stress at the age of 10 days, as well as after a 30-min restraint
stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical
hormone responsiveness was evaluated after i.v. administration of 2 microg/kg
corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and
mineralocorticoid receptor (MR) binding capacities were assessed in the
pituitaries of adult rats. The results showed that at day 10 basal ACTH
concentration was elevated while the cold stress-evoked ACTH response was
attenuated in the dexamethasone-treated rats. As adults, treated rats showed a
suppressed elevation of both ACTH and corticosterone plasma concentrations in
response to restraint, while basal hormonal concentrations were not altered.
There was no difference in the magnitude of the CRH-induced elevation of ACTH and
corticosterone concentrations initially; however, the dexamethasone-treated
animals showed a prolonged secretion of both hormones. These animals also showed
a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone
treatment strongly suppressed body weight gain, and adrenal and thymus weights in
the early phase of postnatal development. By adulthood, the body and adrenal
weights were normalized while thymus weight was greater than in controls. These
findings indicate that neonatal dexamethasone treatment permanently alters HPA
axis activity by reducing stress responses to cold and restraint probably through
supra-pituitary actions, and by decreasing the effectiveness of feedback through
a diminished GR binding in the pituitary.
PMID- 11012845
TI - Glutamatergic regulation of gonadotropin releasing hormone mRNA levels during
development in the mouse.
AB - The aims of these studies were to investigate the time course of the increase in
gonadotropin releasing hormone (GnRH) mRNA levels during sexual development in
the mouse, and to test the hypothesis that the neurotransmitter glutamate
regulates the GnRH secretory system via actions at the level of GnRH gene
expression. GnRH mRNA abundance was estimated by measuring silver grains
generated by in situ hybridization of an 35S-labelled oligonucleotide probe.
There was a significant increase in GnRH mRNA abundance between the day of birth
(P0) and postnatal day 2 (P2) in male mice, but no further increases at later
ages when overt pubertal changes are manifest. GnRH mRNA levels also increased
significantly between P0 and P2 in female mice. Treatment with the glutamate
agonist NMDA caused a significant increase in GnRH mRNA levels in neonatal (P0)
mice and adult male mice within 30 min of treatment, which is consistent with
previous studies in the rat implicating glutamate in the regulation of GnRH mRNA
stability. Treatment with the glutamate antagonist CGP40116 caused an equally
rapid decrease in GnRH mRNA levels in adult mice and in mice on P5 after the
neonatal increase in GnRH gene expression, but was without effect in mice on P0,
prior to the developmental increase. These observations that the effect on GnRH
mRNA levels of blocking endogenous glutamatergic signalling depends upon the
developmental stage suggest that endogenous glutamate maintains GnRH mRNA levels
in adult mouse, and is a potential regulator of the developmental increase seen
in the neonatal period.
PMID- 11012846
TI - Selective blockade of the mineralocorticoid receptor impairs hypothalamic
pituitary-adrenal axis expression of habituation.
AB - The present study investigated the role of mineralocorticoid receptors (MR) and
glucocorticoid receptors (GR) in the expression of habituation of the
hypothalamic-pituitary-adrenal (HPA) axis response to stress. Male rats were
restrained for 1 h per day for six consecutive days. On day 6, 1 h prior to
restraint stress, both restraint-naive and repeatedly restrained rats were
injected s.c. with either vehicle (propylene glycol) or one of three
corticosteroid receptor antagonist treatments: selective MR antagonist (RU28318
or spironolactone), selective GR antagonist (RU40555), or both MR and GR
antagonists combined (RU28318 + RU40555). Blood samples were collected for
corticosterone measurement at the beginning of stress, during stress, and 1 h
after stress termination. Repeated restraint stress produced significant
habituation of corticosterone responses. Acute treatment with the combined MR and
GR antagonists prevented the expression of habituation. When tested alone, the MR
antagonist also blocked the expression of corticosterone-response habituation,
whereas the GR antagonist had no effect. Neither the MR, nor the GR antagonists
alone, significantly altered the corticosterone response to restraint in rats
exposed to restraint for the first time. The final experiment examined the
corticosterone response to a corticotropin releasing hormone (CRH, 3 microg/kg
i.p.) challenge. Neither previous exposure to restraint or acute pretreatment
with the combined MR and GR antagonists (RU28318 + RU40555) altered the
corticosterone response to CRH challenge. This result indicates that the
expression of habituation and its blockade by corticosteroid receptor antagonists
is not a result of altered pituitary-adrenal response to CRH. Overall, this study
suggests that MR plays an important role in constraining the HPA axis response to
restraint stress in restraint-habituated rats. The dependence of the HPA axis on
MR-mediated corticosteroid negative feedback during acute stress may be an
important mechanism that helps maximize the expression of stress habituation and
thereby minimize exposure of target tissues to corticosteroids in the context of
repeated stress.
PMID- 11012847
TI - Drooling: review of the literature and proposals for management.
AB - The aetiology of drooling is described alongside the alternative treatment
strategies for what is a disturbing disorder for many children. The advantages
and disadvantages of each treatment modality are discussed. Conditions for
optimal management are described.
PMID- 11012848
TI - Three-dimensional force measurements on oral implants: a methodological study.
AB - This paper describes a methodology that allows in vitro and in vivo
quantification and qualification of forces on oral implants. Strain gauges are
adapted to the outer surface of 5.5 and 7 mm standard abutments (Branemark
System, Nobel Biocare, Sweden). The readings of the strain gauges are transformed
into a numerical representation of the normal force and the bending moment around
the X- and Y-axis. The hardware and the software of the 3D measuring device based
on the strain gauge technology is explained and its accuracy and reliability
tested. The accuracy level for axial forces and bending moments is 9.72 N and 2.5
N x cm, respectively, based on the current techniques for strain gauged
abutments. As an example, an in vivo force analysis was performed in a patient
with a full fixed prosthesis in the mandible. Since axial loads of 450 N and
bending moments of 70 N x cm were recorded, it was concluded that the accuracy of
the device falls well within the scope of our needs. Nevertheless, more in vivo
research is needed before well defined conclusions can be drawn and strategies
developed to improve the biomechanics of oral implants.
PMID- 11012849
TI - Stress distribution in the temporomandibular joint affected by anterior disc
displacement: a three-dimensional analytic approach with the finite-element
method.
AB - The purpose of this study was to investigate the influences of anterior disc
displacement on TMJ loading during maximum clenching by use of finite-element
analysis. Based on a young human dry skull, an analytic model of the mandible
including the TMJ was developed. In addition to the standard model with normal
disc-condyle relation, two models were designed to simulate various degrees of
anterior disc displacement. In the standard model, compressive stresses were
induced in the anterior, middle and lateral areas on the condyle and glenoid
fossa, whereas tensile stresses were observed in the posterior and medial
regions. In the models with anterior disc displacement, compressive stresses were
recognized in all the areas of TMJ components excluding the bilaminar zone. Shear
stresses in the articular disc and bilaminar zone significantly increased in most
areas. In conclusion, stress distributions in the TMJ with a normal disc position
was substantially different from those with anterior disc displacement,
suggesting that the progress in disc displacement may have some association with
the nature of stress distributions in the TMJ, in the articular disc in
particular.
PMID- 11012850
TI - Sectional prosthesis with hollow obturator portion made of thin silicone layer
over resin frame.
AB - Magnetically retained sectional obturator prostheses, consisting of a hollow
obturator portion made of thin silicone layer over a resin frame and a denture
portion, were fabricated to alleviate some of the limitations of silicone
materials, and applied to two edentulous patients with maxillectomy defects. The
silicone obturator allowed profound engagement of undercuts within the defect,
resulting in adequate retention, support and stability of the prostheses for over
3 years. The patients have achieved improvement in speech and mastication without
complications, by use of the obturator prostheses.
PMID- 11012851
TI - Bolus dimensions in normal chewing.
AB - Samples of 17 different types of chewing gum weighing between 0.3 and 22 g were
presented to eight subjects. After chewing the samples for between 20 and 100
strokes the boluses of gum were removed from the mouth and their length was
measured. Bolus length increased with weight from 0.3 to 4 g, but remained
constant between 4 and 18 g at which point it began to increase once more. The
range of sizes associated with this plateau is similar to the range of sizes of
natural bites with other foods.
PMID- 11012852
TI - Evaluation of stresses caused by dentin pin with finite elements stress analysis
method.
AB - The aim of the present study was to show the dimensions and the amount of
stresses caused by pins on dentin. Mathematically modelled stainless steel and
titanium pins were applied to mandibular first molar teeth with extensive crown
destruction. The stress caused by the pins was examined with the finite elements
method (FEM). In both types of pin, the maximum diffuse and the dense stress
areas were located at the bottom of the pin channel. It is believed that these
stresses should be taken into consideration when evaluating the advantages and
disadvantages of pin application to teeth with destroyed crowns.
PMID- 11012853
TI - Acoustic emissions generated in aged dental composites using a laser
thermoacoustic technique.
AB - The heating up of dental composites by laser will produce acoustic emissions
(AEs) that may be related to fracture mechanisms in the composites. It has been
proved that the mechanical properties of dental composites are affected by
storage in food simulating liquids, i.e. 75% ethanol, which has a solubility
parameter approximating to that of bisphenol glycidyl dimethacrylate (BisGMA)
resin. A new method was innovated to evaluate the laser-induced AEs in dental
composites aged by 75% ethanol solution. Model systems (50/50 BisGMA/TEGDMA resin
filled with 0% and 75 wt.% 5-10 microm silanized BaSiO6) as well as three
commercial composites (Marathon One, Z100 and Herculite XRV) were used in this
study. Nine samples acting as the control group were tested to establish the
correlation of AEs to laser power. The effect of ageing by immersion in 75%
ethanol on AEs and diametral tensile strength (DTS) was then evaluated. A quasi
continuous wave CO2 laser was used to heat up the composites. AEs of frequency
100-200 kHz were collected, filtered, recorded and processed using a 4610 Smart
Acoustic Monitor. Burst patterns, which formally were assumed to be correlated to
fracture mechanisms, were also identified from the data obtained at laser power >
or = 5 W for commercial composites and > or = 4 W for model systems. Higher laser
powers cause the AE to increase for all composites except unfilled model resin.
AEs as a function of power for all aged systems were flat (< 100 events) below 4
W. Emissions then rose sharply to > 1000 events at 7.1 W. Statistically
significant differences were found between the AEs obtained at 5 W (commercial
composites) and those at 4.3 W (model systems) for material systems and storage
times. Marathon One was less affected by the laser and an abrupt change in AE was
found between days 0 and 7 of storage for all commercial composites. The AE value
from the unfilled model resin was found to be significantly different from that
of the model composites. However, they showed an increase in AEs with length of
storage time, which was inversely associated with the decreased tendency of their
immersed DTS values. Laser-induced AEs may be a valuable adjunct to conventional
mechanical testing.
PMID- 11012854
TI - In vivo measurement of colour changes in natural teeth.
AB - It has been observed that teeth become lighter when they are dried. The present
study was designed to quantify these changes and the time taken for tooth colour
to return to normal. The colour of an upper central incisor in each of seven
subjects was measured using a reflectance spectrophotometer before and after
application of a rubber dam and, in another seven subjects before and after
taking a polyvinylsiloxane impression. There were statistically significant
changes in the L*, a* and b* values following rubber dam application and in the
L* value following impression taking. The results demonstrate that teeth become
brighter and less colour saturated after rubber dam application and brighter
after impression taking. The original values were regained after 30 min.
PMID- 11012855
TI - Influence of alteration of occlusal relationship on activity of jaw closing
muscles and mandibular movement during submaximal clenching.
AB - The aim of this study was to investigate the relationships between occlusal
contacts, responses of muscles, and jaw movements during simulated clenching.
Seven healthy human males who possessed complete natural dental arches with
normal occlusion, ranging from 24 to 29 years of age, volunteered for this study.
Acrylic occlusal stops were fabricated for the lower jaw to simulate various
occlusal conditions. Vertical movements of the lower jaw were measured by four
sets of linear variable differential transformers. Simultaneously,
electromyographic (EMG) activity from the bilateral masseter and anterior
temporal muscles was measured. Under experimentally altered occlusal conditions,
the subjects performed clenching tasks at 50% of their maximal voluntary
contraction level. Analysis of EMG responses revealed clenching on the unilateral
occlusal support tended to cause a unilateral activity of the ipsilateral
anterior temporalis. Analysis of the movement amplitude revealed a significant
difference between the experimental occlusal conditions (P < 0.05). Clenching on
unilateral occlusal stops caused a larger upward movement on the contralateral
side. Bilateral first premolar clenching without molar support caused a larger
upward movement of the mandible in the posterior region, whereas bilateral second
molar clenching did not cause a significant upward movement.
PMID- 11012856
TI - Cephalometric estimation of vertical dimension of occlusion.
AB - The literature does not establish a single proven method for determining lower
facial height, which is called the Vertical Dimension of Occlusion (VDO), and the
concept of a vertical comfort range is generally accepted. This study aimed to
test the statistical significance of correlations of mandibular shape versus
lower facial height in occlusion, using cephalometric measurements. Correlations
for 505 consecutive healthy adults were calculated between angles that estimate
the lower facial height and angles that estimate the mandibular shape. The
mandibular angle (gonial) showed a higher coefficient of correlation (r = 0.691)
than the inferior gonial angle. The dispersion remained large, i.e. r2 = 0.478.
Cephalometric measurements, despite theirs imperfections, could help the
practitioner to understand what the best course of treatment would be in order to
obtain a lower facial height in occlusion showing a skeletal harmony with the
mandibular shape.
PMID- 11012857
TI - Morphological interface between hybrid ionomers and dentin with and without smear
layer removal.
AB - To evaluate the micromorphological interface between dentin and several hybrid
ionomer restoratives, a flat dentin surface was obtained on the occlusal surfaces
of extracted human molar teeth after sectioning the enamel with an Isomet saw.
Three poly-acid-modified composite resins, Compoglass, Dyract and F2000, and two
resin-modified glass-ionomer cements, Fuji II LC and Photac-Fil were applied to
the dentin surface. A second section, 2 mm apical from the first one, was made to
produce a dentin segment containing the tested materials. Each disc was then
split fractured along the dentin/material interface. For the poly-acid-modified
composites, one half of the disc was stored in 6 mol/L HCl for 48 h to remove the
dentin. The other was gently decalcified and deprotenized at the interface
between the hybrid ionomer and the dentin. Both halves were then sputtered with
gold and examined using SEM. For resin-modified glass-ionomer, samples were only
evaluated at the interface. The three poly-acid-modified composite resins showed
the formation of hybrid layers and resin tags at the interface to the dentin.
Removal of the smear layer significantly improves hybridization of these
materials. Also, Fuji II LC produced a hybrid layer while the Photac-Fil showed
no evidence of hybridization.
PMID- 11012858
TI - The temporomandibular opening index (TOI) in patients with closed lock and a
control group with no temporomandibular disorders (TMD): an initial study.
AB - Mandibular movement may be assessed by measuring maximum mouth opening. This is a
linear measurement from the maxillary to the mandibular incisal edge and is
affected by gender, age and ramus length. It cannot be used to classify patients.
The temporomandibular opening index (TOI) appears to be independent of these
variables and has been shown to differ for different categories of patients with
temporomandibular disorders (TMD). This study examined the TOI in a group of 11
patients with closed lock and a control group of 11 individuals with no signs or
symptoms of TMD. The group with closed lock had a significantly different TOI
from that of the control group (P < 0.001) according to the Mann-Whitney U-test.
This suggests that the TOI may have greater diagnostic value than linear mouth
opening.
PMID- 11012859
TI - A study on the mandibular movement of anterior openbite patients.
AB - The purpose of this study was to compare the mandibular movements of anterior
openbite patients using those of normal bite (angle class I) patients, to
ascertain which components of mandibular movement are different in the two
groups, and to use this information for occlusal treatment. The Saphon Visi
trainer Model 3 and the Denar Pantronic were used to record mandibular movement
and a Pantronic survey was performed using an arbitrary hinge axis, according to
manufacturer's instructions. The subjects were 43 adults and included 28 subjects
presenting with acceptable normal occlusion (angle class I) with no sign of TM
dysfunction syndrome (TMD) and 15 subjects with anterior openbite with no
anterior guidance. In the anterior openbite group, the average anterior and
lateral condylar inclination, maximum opening and the distance between the
intercuspal position with retruded contact position distance (anterior-posterior)
were significantly lower than normal. The results suggest that in openbite
patients the condyle inclination is flatter and the function of the TMJ is more
restricted than in the mandibular movements of the normal group. It is hoped that
these results will be useful for the correction of the anterior openbite
condition.
PMID- 11012861
TI - Simulated driving performance following prolonged wakefulness and alcohol
consumption: separate and combined contributions to impairment.
AB - The separate and combined effects of prolonged wakefulness and alcohol were
compared on measures of subjective sleepiness, simulated driving performance and
drivers' ability to judge impairment. Twenty-two males aged between 19 and 35
years were tested on four occasions. Subjects drove for 30 min on a simulated
driving task under conditions determined by the factorial combination of 16 and
20 h of wakefulness and blood alcohol concentrations of 0.00 and 0.08%. The
simulated driving session took place 30 min postingestion; subjects in the two
alcohol conditions participated in a second 30-min driving session 90-min
postingestion. Subjects made simultaneous ratings of their impairment while
driving and retrospective ratings at the end of each test session. Subjective
sleepiness measures were completed before and after each driving session. The
combination of 20 h of prolonged wakefulness and alcohol produced significantly
lower ratings of subjective sleepiness and driving performance that was worse,
but not significantly so, than would be expected from the additive effects of
each condition alone. Driving performance was always worse in the second driving
session, during the elimination phase of alcohol metabolism, despite blood
alcohol concentrations being lower than during the first driving session. There
was a modest association between perceived and actual impairments in driving
performance following prolonged wakefulness and alcohol. The findings suggest
that the combination of prolonged wakefulness and alcohol consumption produced
greater decrements in simulated driving performance than each condition alone and
that drivers have only a modest ability to appreciate the magnitude of their
impairment.
PMID- 11012860
TI - Functional neuroimaging of normal human sleep by positron emission tomography.
AB - Functional neuroimaging using positron emission tomography has recently yielded
original data on the functional neuroanatomy of human sleep. This paper attempts
to describe the possibilities and limitations of the technique and clarify its
usefulness in sleep research. A short overview of the methods of acquisition and
statistical analysis (statistical parametric mapping, SPM) is presented before
the results of PET sleep studies are reviewed. The discussion attempts to
integrate the functional neuroimaging data into the body of knowledge already
acquired on sleep in animals and humans using various other techniques
(intracellular recordings, in situ neurophysiology, lesional and pharmacological
trials, scalp EEG recordings, behavioural or psychological description). The
published PET data describe a very reproducible functional neuroanatomy in sleep.
The core characteristics of this 'canonical' sleep may be summarized as follows.
In slow-wave sleep, most deactivated areas are located in the dorsal pons and
mesencephalon, cerebellum, thalami, basal ganglia, basal forebrain/hypothalamus,
prefrontal cortex, anterior cingulate cortex, precuneus and in the mesial aspect
of the temporal lobe. During rapid-eye movement sleep, significant activations
were found in the pontine tegmentum, thalamic nuclei, limbic areas (amygdaloid
complexes, hippocampal formation, anterior cingulate cortex) and in the posterior
cortices (temporo-occipital areas). In contrast, the dorso-lateral prefrontal
cortex, parietal cortex, as well as the posterior cingulate cortex and precuneus,
were the least active brain regions. These preliminary studies open up a whole
field in sleep research. More detailed explorations of sleep in humans are now
accessible to experimental challenges using PET and other neuroimaging
techniques. These new methods will contribute to a better understanding of sleep
functions.
PMID- 11012862
TI - Diurnal variations in the waking EEG: comparisons with sleep latencies and
subjective alertness.
AB - Daytime measures of sleep latency and subjective alertness do not correlate with
one another, suggesting that they assess different aspects of alertness. In
addition, their typical diurnal variations show very different time courses.
Quantitative analysis of the waking electroencephalogram (EEG) has been proposed
as an objective measure of alertness, but it is not clear how it compares with
other measures. In this study, the waking EEG was measured in the daytime to
determine the presence of diurnal variations in the activity of standard
frequency bands and to compare these variations with the temporal patterns
typical of sleep propensity and subjective alertness. Alertness was evaluated in
four men and 12 women, aged 19-33 y. Assessments were conducted every 2 h, from
10.00 to 24.00, in the following order: a visual analogue scale of alertness, a
waking EEG recording and a sleep latency test. The waking EEG was recorded with
eyes open. For each recording session, 32-60 s of artefact-free signals were
selected from the C3/A2 derivation, then subjected to amplitude spectral
analysis. Four EEG frequency bands showed significant diurnal variations: delta,
theta, sigma and beta1. None of these variations showed a significant correlation
with the temporal patterns of sleep latencies or subjective alertness. At the
individual level, however, theta band activity increased when subjective
alertness decreased, suggesting that the theta band can be used to monitor
variations in alertness in a given individual, even at the moderate levels of
sleepiness experienced during the daytime.
PMID- 11012863
TI - Gender-related sleep differences in neonates in thermoneutral and cool
environments.
AB - Although thermoregulation and sleep exhibit gender differences in adults, the
question is still debated in neonates. The aim of this study was to examine the
relationship between gender-related sleep differences and cool defence mechanisms
in neonates. Sleep and thermoregulation were recorded in healthy preterm neonates
(21 boys and 17 girls, 37 +/- 2 weeks post-conceptional age) exposed to
thermoneutral and cool conditions. Sleep was analysed for continuity and
structure. Although the cool exposure did not strongly impair body homeothermia,
sleep was altered but without any significant gender difference. However, when
data recorded under each of the thermal conditions were pooled, some gender
differences emerged: boys slept less, with more wakefulness after sleep onset,
more active sleep and less quiet sleep than girls. In contrast to sleep
architecture, most of the sleep continuity parameters exhibited greater
variability in boys than in girls. This variability may bias the statistical
analyses and probably explains the varying conclusions reported in the literature
regarding gender-specific sleep-related differences.
PMID- 11012864
TI - Tactile arousal threshold of sleeping king penguins in a breeding colony.
AB - The tactile arousal threshold of sleeping birds has not been investigated to
date. In this study, the characteristics of this threshold were assessed by
stimulating either the upper back or a foot of two groups (one cutaneous site per
group) of 60 sleeping king penguins (Aptenodytes patagonica) in the breeding
colony of Baie du Marin (Crozet Archipelago). Increasing weights were put onto
one of the feet or the upper back of individuals that had been sleeping for more
than 5 min until they showed behavioural signs of arousal (head raising). The
weight applied to the upper back that was needed to awaken a sleeper (837 +/- 73
g) was 20 times greater than that applied to a foot (38 +/- 6 g). In terms of
pressure, the difference remained five times higher for the back (209 +/- 18
g/cm(2)) than the foot (40 g +/- 7 g/cm(2)). Because the king penguin incubates
its single egg and rears its young chick on its feet, the low threshold measured
at this level could be viewed as an adaptation against progeny predation.
Sleepers are frequently bumped by conspecifics walking through the colony. The
increased arousal threshold associated with tactile stimulation of the back may
help to preserve sleep continuity under these conditions.
PMID- 11012865
TI - Rest and activity states in a gray whale.
AB - The behaviour of a female gray whale (Eschrichtius robustus) that had been
rescued 14 months previously was recorded continuously on a video-recorder for 9
days at 'Sea World' in San Diego. On average, during the first six recording
days, active wakefulness accounted for 37.9 +/- 1.7% of each 24 h; transitional
stage for 17.4 +/- 1.4% and rest for 41.2 +/- 1.7%. In the rest stage the whale
was lying on the bottom of the pool (13.2 +/- 1.7%) or hanging on the surface
(28. 0 +/- 1.7%). During the rest stage, it was immobile most of the time and
moved only for respiration. In the rest stage both eyes could be open, one eye
could be open while the other was closed or, more rarely, both eyes could be
closed. Characteristic jerks of the head, neck and sometimes of the whole body
were observed in the whale during the rest stage. Most jerks were single and only
10% of all jerks were serial (occurring within 10 s of a prior jerk). Eyelid
movements accompanied 40% of jerks. In two episodes, intense jerks followed each
other continuously for 3 and 4 s and were accompanied by eyelid movements. These
jerks resembled the twitches characteristic of paradoxical sleep in terrestrial
mammals. During these episodes the whale was falling slowly onto its side and
subsequently started to swim in the pool.
PMID- 11012866
TI - Does caffeine confound relationships among adrenergic tone, blood pressure and
sleep apnoea?
AB - The purpose of this study was to determine whether caffeine consumption confounds
the relationship among adrenergic tone, as measured by urinary norepinephrine
(NE), blood pressure (BP) and obstructive sleep apnoea (OSA). Data were analysed
using correlation and regression analysis, analysis of covariance and t-tests.
Subjects included normotensives and hypertensives with and without OSA: 38 men,
23 women, aged 30-60 y; 100-150% of ideal body weight; without other major
illness. Patients were studied using polysomnography, caffeine consumption was
assessed, 24-h urinary NE levels were examined and ambulatory BP was recorded.
Patients with OSA (N=27) reported significantly greater caffeine consumption than
those without OSA (N=34) (295 vs. 103 mg, P=0.010), but caffeine was not
significantly correlated with their ambulatory BP. In contrast, NE excretion
correlated with caffeine consumption (r=0.24, P=0.041), apnoea severity (r=0.65,
P < 0.001) and BP (r=0.34, P < 0.005). Significant OSA-NE and BP-NE relationships
remained even after controlling for caffeine consumption. Patients with OSA
consumed nearly three times the amount of caffeine as patients without OSA. While
caffeine partially explains the increased adrenergic tone in patients with OSA
and the relationship between BP and NE, it does not appear to contribute
significantly to the relationship between OSA and elevated BP.
PMID- 11012867
TI - EEG arousals and awakenings in relation with periodic leg movements during sleep.
AB - It is known that periodic leg movements are frequently accompanied by full
awakenings or by signs of EEG arousals. The time relationship of these EEG
arousals with leg movements varies from patient to patient. They may precede or
follow leg movements or occur simultaneously. It is not clear whether these
arousals trigger leg movements or, alternatively, whether both EEG arousals and
leg movements are separate expressions of a common pathophysiological mechanism.
We investigated the temporal relationship of five EEG arousals, such as alpha
activity, K-complexes, spindles, K-alpha, K-spindle activities and awakenings,
with leg movements in 10 periodic leg movement patients. These EEG arousals were
considered to be associated with leg movements if they occurred 10 s before/after
or simultaneously with the onset of right or left tibialis muscle EMG potentials.
It was found that 49.19% of EEG arousals occurred before leg movements, 30.61%
occurred simultaneously and 23.18% occurred just after leg movements. The number
of EEG arousals was significantly higher in the 10 s preceding leg movement than
simultaneously or in the 10 s following. Alpha activity was the phenomenon
associated most frequently with leg movements, irrespective of its temporal
organization and was significantly higher during the 10 s preceding movement.
Spindle and K-spindle activities were significantly higher before leg movement,
whereas K-complex activity was significantly more frequent during leg movements.
The number of awakenings was significantly higher after leg movements than
simultaneously. These results indicated that leg movements are not primary, but
rather are a phenomenon associated with an underlying arousal disorder.
PMID- 11012868
TI - Computerized endopharyngeal myotonometry (CEM): a new method to evaluate the
tissue tone of the soft palate in patients with obstructive sleep apnoea
syndrome.
AB - This study compared the tissue tone of the soft palate in nonsnoring subjects and
patients with obstructive sleep apnoea syndrome (OSAS) during wakefulness. Here,
tissue tone means the biomechanical property of the tissue which can be
characterized by two main parameters: stiffness and elasticity. Tissue tone
includes both structural and neural components. A new method to evaluate the
tissue tone of the soft palate was used - computerized endopharyngeal
myotonometry (CEM). This method records and analyses the response of the soft
palate tissues to a brief mechanical impact. The method enabled us to evaluate
the most important parameters of tissue tone: stiffness, which is expressed as a
frequency; and elasticity, expressed as a logarithmic decrement of the damped
oscillation. First, a self-reported questionnaire was completed about the medical
history of the subjects. Subjects then underwent a physical examination of the
oropharynx and polysomnography with overnight pulse oximetry. The results of the
CEM method indicated that patients with OSAS show an increased stiffness of the
soft palate tissues (20.3, SD 4.7 Hz) compared with nonsnoring subjects (12.2, SD
1.8 Hz). In patients with sleep apnoea, elasticity is not increased in a similar
way to stiffness. Thus, the disproportion between tissue stiffness and elasticity
of the soft palate is a measure of the pathological changes in patients with
sleep apnoea.
PMID- 11012869
TI - Increased sodium-proton antiporter activity in patients with obstructive sleep
apnoea.
AB - Cytosolic pH (pH(i)) and the activity of the sodium-proton antiporter (Na(+)/H(+)
antiporter) were measured in lymphocytes from 22 patients with obstructive sleep
apnoea and from 24 age-matched healthy subjects (Controls). The cellular
Na(+)/H(+) antiporter was measured spectrophotometrically using a pH-sensitive
fluorescent dye after intracellular acidification using sodium propionate.
Resting pHi was similar in lymphocytes from patients with obstructive sleep
apnoea and from controls (7.36 +/- 0.20, n=22; vs. 7.35 +/- 0.19, n=24; mean +/-
SD). The Na(+)/H(+) antiporter activity was significantly higher in patients with
obstructive sleep apnoea than in controls (11.87 +/- 3.26 x 10(-3) pH(i)/s vs.
4.38 +/- 1.40 x 10(-3) pH(i)/s; P < 0. 0001). The apparent affinity of the Na+/H+
antiporter was not significantly different between the groups (6.90 +/- 0.23 vs.
6.87 +/- 0.20). In patients with obstructive sleep apnoea the activity of the
Na(+)/H(+) antiporter remained stable during the night. The activity of the
Na(+)/H(+) antiporter was 13.49 +/- 4.80 x 10(-3) pH(i)/s at 20.00 and 13.26 +/-
6.13 x 10(-3) pH(i)/s at 02.00. From the present results it is concluded that an
increased cellular Na(+)/H(+) antiporter activity may be a genetic marker for
patients who are predisposed to obstructive sleep apnoea.
PMID- 11012870
TI - Excessive daytime sleepiness in patients suffering from different levels of
obstructive sleep apnoea syndrome.
AB - Excessive daytime sleepiness (EDS) is a frequent symptom of patients with
obstructive sleep apnoea (OSA). EDS is a high-risk factor for accidents at work
and on the road. Thirty untreated patients with different levels of severity of
OSA were studied concerning night sleep and EDS. The criterion for severity was
the respiratory disturbance index (RDI): 15 patients were classified as
'moderately' apnoeic (RDI < 40), 15 as 'severely' apnoeic (RDI > 40). Following
night-time polysomnography, objective and subjective aspects of EDS were studied.
To assess objective EDS the Maintenance of Wakefulness Test (MWT) and a computer
based vigilance performance test were used. Subjective EDS was determined using
the Stanford Sleepiness Scale (SSS), the Epworth Sleepiness Scale (ESS) and the
Visual Analogue Scales for Performance (VAS-P) and Tiredness (VAS-T). Well-being
was assessed using the Scale of Well-Being by von Zerssen (Bf-S/Bf-S'). Severe
apnoea patients spent more time in stage 1 and less in slow-wave sleep. MWT
latencies tended to be shorter in the severe apnoea group. Vigilance testing
revealed no group differences. Patients with moderate apnoea described themselves
as more impaired in all subjective scales, but only SSS scores reached
statistical significance. Our results suggest that there is no simple correlation
between polysomnographic and respiratory sleep variables at night on the one
hand, and the extent of EDS on the other hand. Furthermore, subjective and
objective evaluation of EDS does not yield the same results. New approaches which
allow a more detailed analysis of night sleep and daytime function are required
to identify high-risked patients.
PMID- 11012871
TI - Quality of life assessment of treatment with dental appliance or UPPP in patients
with mild to moderate obstructive sleep apnoea. A prospective randomized 1-year
follow-up study.
AB - The objectives of this study were: to evaluate the change in the three quality of
life (QOL) dimensions of vitality, contentment and sleep before intervention and
1 year after treatment with a dental appliance or uvulopalatopharyngoplasty
(UPPP); to compare the effect of treatment between these two treatment groups on
these three dimensions; and to determine the relation between the QOL scores and
somnographic values. Ninety-five patients with mild to moderate obstructive sleep
apnoea (OSA) (AI > 5) were randomly allocated to either a dental appliance or
UPPP treatment group. Seven patients withdrew after randomization but before
treatment, leaving 88 patients eligible for treatment. The patients were examined
using somnography and administered the Minor Symptoms Evaluation-Profile (MSE-P),
a QOL questionnaire, before and 1 year after intervention. Thirty-seven patients
in the dental appliance group and 43 in the UPPP group completed the 1-year
follow-up. The mean values for the three dimensions vitality, contentment and
sleep improved significantly 1 year after intervention in the dental appliance
and UPPP groups. No difference in the QOL scores at baseline was noted between
the groups. One year after intervention the UPPP group showed significantly more
contentment than the dental appliance group. In contrast, vitality and sleep
dimensions did not differ between the two treatment groups. No significant
correlations were observed between the QOL scores and somnographic values. In
conclusion, quality of life improved significantly in the dental appliance and
UPPP groups 1 year after intervention. However, the dental appliance group showed
a lower level of contentment than the UPPP group, even though the somnographic
values were superior in the former group.
PMID- 11012872
TI - Night-time sleep and daytime sleepiness in narcolepsy.
AB - This report describes night-time sleep and daytime sleepiness in a large (N=530)
sample of patients meeting the International Classification of Sleep Disorders
criteria for diagnosis of narcolepsy. Sleep data were obtained from
polysomnographic recordings on two consecutive nights. Sleepiness was assessed
using the Multiple Sleep Latency Test, the Maintenance of Wakefulness Test and
the Epworth Sleepiness Scale. Analysis revealed that sleep was mild to moderately
disturbed on both recording nights. A first-night effect was suggested by
decreased REM latency and increased percentage REM and slow-wave sleep on the
second night. Sleepiness and sleep disturbance varied across patient subgroups
created based on patient ethnicity and on the presence/absence of cataplexy,
sleep apnoea, and periodic limb movements. Covariation of sleep and sleepiness
measures across patients was significant but weak. Strong association was found
between subgroup means of sleep and sleep disturbance measures. The findings
reported here show that sleepiness and sleep disturbance vary across patient
subgroups and that sleep disturbance is related to, although unable to account,
for the pathological sleepiness of narcolepsy.
PMID- 11012873
TI - Treatment of advanced renal failure: low-protein diets or timely initiation of
dialysis?
AB - Until 1996, no guidelines existed for the initiation of dialysis in patients with
progressive renal failure. The publication of the National Kidney Foundation
Dialysis Outcome Quality Initiative guidelines has generated a debate on the
management of advanced renal failure and the role of low-protein diets (LPDs). We
performed a review of the literature to identify articles on the initiation of
dialysis and LPDs, particularly those since 1996. Delayed referral of patients is
widespread in both the United States and Europe, and almost 25% of patients are
started on dialysis at a glomerular filtration rate (GFR) of <5 mL/min/1.73 m2.
There is a high prevalence of malnutrition at the time of first dialysis, which
progressively improves upon initiation of dialysis. There is no evidence
regarding the efficacy or safety of LPDs in nondiabetic patients younger than 70
years old [approximately 40% of U.S. incident end-stage renal disease (ESRD)
patients] and in diabetics with GFR <25 mL/min/1.73 m2 (>40% of incident U.S.
ESRD). In nondiabetics who are younger than 70 years old, adherence to LPD for
four to five years can be estimated to result in a delay in dialysis by 6 to 11
months. However, suboptimal energy intake is widespread in advanced renal
failure, which declines further upon institution of LPD. Even nutritionally sound
patients develop subclinical nutritional decline despite intense counseling.
There are no data on the efficacy or safety of LPD in subgroups that constitute
approximately 80% of incident ESRD patients. Concerns still exist regarding their
nutritional safety in the remainder. Initiation of dialysis results in improved
nutritional status and should be considered in a timely fashion.
PMID- 11012874
TI - Connective tissue growth factor: potential role in glomerulosclerosis and
tubulointerstitial fibrosis.
AB - Transforming growth factor beta (TGF-beta) is a pivotal driver of
glomerulosclerosis and tubulointerstitial fibrosis in renal diseases. Because TGF
beta also plays important anti-inflammatory and antiproliferative roles in
mammalian systems, there has been a recent drive to elucidate downstream
mediators of TGF-beta's pro-fibrotic effects with the ultimate goal of developing
new anti-fibrotic strategies for treatment of chronic diseases. Connective tissue
growth factor (CTGF) belongs to the CCN family of immediate early response genes.
Several lines of evidence suggest that CTGF is an important pro-fibrotic molecule
in renal disease and that CTGF contributes to TGF-beta bioactivity in this
setting. CTGF expression is increased in the glomeruli and tubulointerstium in a
variety of renal disease in association with scarring and sclerosis of renal
parenchyma. In model systems in vitro, mesangial cell CTGF expression is induced
by high extracellular glucose, cyclic mechanical strain and TGF-beta. Recombinant
human CTGF augments the production of fibronectin and type IV collagen by
mesangial cells and the effects of high glucose on mesangial cell CTGF expression
and matrix production are attenuated, in part, by anti-TGF-beta antibody. In
aggregate, these observations identify CTGF as an attractive therapeutic target
in fibrotic renal diseases.
PMID- 11012875
TI - Thirteen novel mutations of the replicated region of PKD1 in an Asian population.
AB - BACKGROUND: Mutations of PKD1 are thought to account for approximately 85% of all
mutations in autosomal dominant polycystic kidney disease (ADPKD). The search for
PKD1 mutations has been hindered by both its large size and complicated genomic
structure. To date, few mutations that affect the replicated segment of PKD1 have
been described, and virtually all have been reported in Caucasian patients.
METHODS: In the present study, we have used a long-range polymerase chain
reaction (PCR)-based strategy previously developed by our laboratory to analyze
exons in the replicated region of PKD1 in a population of 41 unrelated Thai and 6
unrelated Korean families with ADPKD. We have amplified approximately 3.5 and
approximately 5 kb PKD1 gene-specific fragments (5'MR and 5'LR) containing exons
13 to 15 and 15 to 21 and performed single-stand conformation analysis (SSCA) on
nested PCR products. RESULTS: Nine novel pathogenic mutations were detected,
including six nonsense and three frameshift mutations. One of the deletions was
shown to be a de novo mutation. Four potentially pathogenic variants, including
one 3 bp insertion and three missense mutations, were also discovered. Two of the
nonconservative amino acid substitutions were predicted to disrupt the three
dimensional structure of the PKD repeats. In addition, six polymorphisms,
including two missense and four silent nucleotide substitutions, were identified.
Approximately 25% of both the pathogenic and normal variants were found to be
present in at least one of the homologous loci. CONCLUSION: To our knowledge,
this is the first report of mutation analysis of the replicated region of PKD1 in
a non-Caucasian population. The methods used in this study are widely applicable
and can be used to characterize PKD1 in a number of ethnic groups using DNA
samples prepared using standard techniques. Our data suggest that gene conversion
may play a significant role in producing variability of the PKD1 sequence in this
population. The identification of additional mutations will help guide the study
of polycystin-1 and better help us to understand the pathophysiology of this
common disease.
PMID- 11012876
TI - Structural analysis of the 11beta-hydroxysteroid dehydrogenase type 2 gene in end
stage renal disease.
AB - BACKGROUND: Mutations in the 11beta-hydroxysteroid dehydrogenase type 2
(11betaHSD2) gene cause a rare form of low-renin hypertension leading to end
stage renal disease (ESRD) in some affected subjects. To date, no search for
mutations in the HSD11B2 gene was performed in a large population to obtain an
estimate its prevalence. METHODS: The HSD11B2 gene was analyzed in 587 subjects,
including 260 ESRD patients (either dialysis or transplanted) for mutations in
the exons 2 through 5 and corresponding intronic regions by polymerase chain
reaction (PCR) using appropriate overlapping primers, gel analysis by single
strand conformational polymorphism (SSCP), and sequencing of identified migration
variants. RESULTS: The prevalence of single-nucleotide polymorphisms (SNPs) in
ESRD patients and controls was 26%. The following genetic variants were found
among all subjects investigated: exon 2 T442G (Leu148/Val, N = 70) and C470A
(Thr156/Thr, N = 67), exon 3 G534A (Glu178/Glu, N = 69), and exon 5 C1274T
(Asp388/Asp, N = 2). Four SNPs were identified in intron 4 only. In the control
population, the prevalence of the variants Leu148 and Thr156 was 14% each. Glu178
was 11%, while no variants were found in exon 5. In ESRD patients, the prevalence
of the variant Leu148 was 9%, and Thr156 was 8%. Glu178 was 13%, while the Asp388
variant was 0.7%. In patients with a short duration between the time of diagnosis
of the renal disease and the onset of ESRD, the prevalence of the Leu148 and
Glu178 variants was higher than in subjects with slowly progressing renal
disease. The 11betaHSD2 activity of all of these SNPs is predictably unaltered.
CONCLUSIONS: There is a high prevalence of SNPs of the HSD11B2 gene, without
causing exonic mutations generating a 11betaHSD2 enzyme with altered activity.
Based on statistical analyses, the frequency of homozygosity for mutated alleles
of the HSD11B2 gene can be derived as <1/250,000 when a Caucasian population is
considered.
PMID- 11012877
TI - Cerivastatin prevents angiotensin II-induced renal injury independent of blood
pressure- and cholesterol-lowering effects.
AB - BACKGROUND: Statins are effective in prevention of end-organ damage; however, the
benefits cannot be fully explained on the basis of cholesterol reduction. We used
an angiotensin II (Ang II)-dependent model to test the hypothesis that
cerivastatin prevents leukocyte adhesion and infiltration, induction of inducible
nitric oxide synthase (iNOS), and ameliorates end-organ damage. METHODS: We
analyzed intracellular targets, such as mitogen-activated protein kinase and
transcription factor (nuclear factor-kappaB and activator protein-1) activation.
We used immunohistochemistry, immunocytochemistry, electrophoretic mobility shift
assays, and enzyme-linked immunosorbent assay techniques. We treated rats
transgenic for human renin and angiotensinogen (dTGR) chronically from week 4 to
7 with cerivastatin (0.5 mg/kg by gavage). RESULTS: Untreated dTGR developed
hypertension, cardiac hypertrophy, and renal damage, with a 100-fold increased
albuminuria and focal cortical necrosis. dTGR mortality at the age of seven weeks
was 45%. Immunohistochemistry showed increased iNOS expression in the endothelium
and media of small vessels, infiltrating cells, afferent arterioles, and
glomeruli of dTGR, which was greater in cortex than medulla. Phosphorylated
extracellular signal regulated kinase (p-ERK) was increased in dTGR; nuclear
factor-kappaB and activator protein-1 were both activated. Cerivastatin decreased
systolic blood pressure compared with untreated dTGR (147 +/- 14 vs. 201 +/- 6 mm
Hg, P < 0.001). Albuminuria was reduced by 60% (P = 0.001), and creatinine was
lowered (0.45 +/- 0.01 vs. 0.68 +/- 0.05 mg/dL, P = 0. 003); however, cholesterol
was not reduced. Intercellular adhesion molecule-1 and vascular cell adhesion
molecule-1 expression was diminished, while neutrophil and monocyte infiltration
in the kidney was markedly reduced. ERK phosphorylation and transcription factor
activation were reduced. In addition, in vitro incubation of vascular smooth
muscle cells with cerivastatin (0.5 micromol/L) almost completely prevented the
Ang II-induced ERK phosphorylation. CONCLUSION: Cerivastatin reduced
inflammation, cell proliferation, and iNOS induction, which led to a reduction in
cellular damage. Our findings suggest that 3-hydroxy-3-methylglutaryl coenzyme
(HMG-CoA) reductase inhibition ameliorates Ang II-induced end-organ damage. We
suggest that these effects were independent of cholesterol.
PMID- 11012878
TI - Stretch activation of jun N-terminal kinase/stress-activated protein kinase in
mesangial cells.
AB - BACKGROUND: Mesangial cells (MCs) grown on extracellular matrix (ECM)-coated
plates and exposed to cyclic stretch/relaxation proliferate and produce ECM
protein, suggesting that this may be a useful in vitro model for MC behavior in
response to increased physical forces. The induction of c-fos in response to MC
stretch has been shown. Stimuli that lead to c-fos induction pass through mitogen
activated protein (MAP) kinase pathways. We have seen early activation of jun N
terminal kinase/stress-activated protein kinase (SAPK/JNK) in MCs exposed to
cyclic stretch. Accordingly, we studied SAPK/JNK activation in stretched MCs and
the downstream consequences of this signaling. METHODS: MCs (passages 5 to 10)
cultured on type 1 collagen-coated, flexible-bottom plates were exposed to 2 to
60 minutes of cyclic strain (60 cycles per minute) by generation of vacuums of
10 to -27 kPa, inducing approximately 16 to 28% maximum elongation in the
diameter of the surfaces. Control MCs were grown on coated rigid bottom plates.
Protein levels (by Western blot) and activity assays for SAPK/JNK were performed
under these conditions. We observed marked activation at -18 kPa and above and at
two minutes, and then we studied activation mechanisms under these conditions.
Nuclear protein binding to activator protein-1 (AP-1) consensus sequences was
also examined. The role of calcium was studied with EGTA and BAPTA-AM to chelate
extra- and intracellular calcium, respectively. Protein kinase C (PKC) was down
regulated by incubation with phorbol ester (PMA) for 24 hours prior to stretch.
In unstretched MCs, A23187 was used as a calcium ionophore, and PKC was up
regulated with PMA application for 30 minutes to determine the effects on
SAPK/JNK. Nuclear protein binding to AP-1 was also determined under these
conditions. The effects of stretch, acute PMA, and A23187 on fibronectin mRNA
levels were studied using reverse transcriptase-polymerase chain reaction (RT
PCR). RESULTS: Cyclic strain/relaxation led to increased SAPK/JNK activity only
at two minutes and -18 kPa and above. The activation of SAPK/JNK was dependent on
intracellular calcium, with BAPTA-AM almost completely abrogating the response to
stretch. EGTA was without effect. Down-regulation of PKC also led to a diminution
of activity. In static cells, the calcium ionophore A23187 increased SAPK/JNK
activity, and this was potentiated by acute PMA. Stretch, acute PMA, and A23187
all increased nuclear protein binding to AP-1 consensus sequences. mRNA levels
for fibronectin were increased by stretch in MCs and by PMA and A23187 in static
MCs. No change was observed in the amount of SAPK/JNK protein present in
stretched MCs by Western blot. CONCLUSIONS: Stretch leads to early activation of
SAPK/JNK in MCs. This is dependent on intracellular calcium and PKC and can be
replicated by activation of these stimuli in static MCs. A downstream induction
of nuclear protein binding to AP-1 consensus sequences was seen in a pattern that
was completely concordant with the SAPK/JNK induction.
PMID- 11012879
TI - Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal
failure.
AB - BACKGROUND: Resistance to the action of parathyroid hormone (PTH) has been
demonstrated in end-stage renal failure and is considered to be important in the
pathogenesis of secondary hyperparathyroidism. The mechanism of resistance is
unknown. However, altered regulation of cellular PTH/PTH-related protein
(PTH/PTHrP) receptor (PTH1R) has been assumed to be important. METHODS: We have
used in situ hybridization to examine PTH1R mRNA expression by osteoblasts in
human bone and have compared the expression in high- and low-turnover renal bone
disease, high-turnover nonrenal bone disease (healing fracture callus and Pagetic
bone), and normal bone. Bone biopsies were formalin fixed,
ethylenediaminetetraacetic acid decalcified, and paraffin wax embedded. A 1.8 kb
PTH1R cDNA probe, labeled with 35S, was used, and the hybridization signal was
revealed by autoradiography. The density of signal over osteoblasts was
quantitated using a semiautomated Leica image analysis software package. RESULTS:
The mean density of PTH1R mRNA signal over osteoblasts in renal high-turnover
bone was only 36% of that found in nonrenal high-turnover bone (P < 0.05) and 51%
of that found in normal bone (P < 0.05). Osteoblast PTH1R mRNA signal in adynamic
bone from individuals with diabetes mellitus was 28% of normal bone (P < 0.05)
and 54% of that found in renal high-turnover bone (P < 0.05). CONCLUSIONS: These
results demonstrate a down-regulation of osteoblast PTH1R mRNA in end-stage renal
failure in comparison to normal and high-turnover bone from otherwise healthy
individuals, and provide an insight into the mechanisms of "skeletal resistance"
to the actions of PTH.
PMID- 11012880
TI - Functional modulation of the mineralocorticoid receptor by cis
diamminedichloroplatinum (II).
AB - BACKGROUND: Renal salt wasting and hypotension are some of the frequent
complications in patients treated with cis-diamminedichloroplatinum (II) (cDDP),
and it is suggested that cDDP produces an abnormality in the renin-angiotensin
system. However, not only the underlying mechanism but also prophylactic
treatment of this cDDP toxicity remains unknown. In the present study, we
investigated the molecular mechanism of this cDDP-induced disturbance of renal
sodium handling with focusing on the effect of cDDP on mineralocorticoid receptor
(MR) function. METHODS: The effect of cDDP was studied on nuclear translocation,
DNA binding activity, and transactivation function of the MR. RESULTS: In a
transient transfection assay, cDDP suppressed MR-dependent reporter gene
expression. This cDDP-mediated repression of MR function, at least in part, is
suggested to be due to the generation of reactive oxygen species and a subsequent
decrease in ligand-dependent nuclear translocation and suppression of the
interaction with DNA of the MR. This redox-dependent repression of MR function
both in vitro and in vivo was reversed by treatment with reducing reagents.
Moreover, cDDP, most possibly via formation of DNA adducts, inhibited MR-DNA
interaction in a redox-independent fashion. CONCLUSIONS: MR function is impaired
by cDDP at multiple levels, via redox-dependent and -independent mechanisms.
PMID- 11012881
TI - Nephrin in experimental glomerular disease.
AB - BACKGROUND: The recently identified gene NPHS1 with its mutations causing
congenital nephrotic syndrome of the Finnish type (CNF) is highly promising in
providing new understanding of pathophysiology of proteinuria. Earlier we cloned
a rat NPHS1 homologue, as well as characterized and raised antibodies to the
respective protein product nephrin. METHODS: Changes in the expression levels of
nephrin-specific mRNA in commonly used experimental models of proteinuria were
examined using semiquantitative reverse transcription-polymerase chain reaction,
immunofluorescence, and immunoelectron microscopy (IEM) of nephrin. RESULTS:
Notably, a 40% down-regulation of the nephrin-specific mRNA of cortical kidney
was seen already at day 3 after induction of the puromycin aminonucleoside
nephrosis (PAN), while no major elevation of urinary protein secretion was seen
at this stage. A further decrease of 80% of nephrin message was seen at the peak
of proteinuria at day 10. A similar decrease of up to 70% from the basal levels
was seen in mercuric chloride-treated rats. Changes in the protein expression
paralleled those of the mRNA in indirect immunofluorescence. Interestingly, a
remarkable plasmalemmal dislocation from the normal expression site at the
interpodocyte filtration slits could be observed in IEM. CONCLUSIONS: Nephrin
appears to be an important causative molecule of proteinuria and shows a
remarkable redistribution from the filtration slits to the podocyte plasma
membrane, especially in PAN.
PMID- 11012882
TI - Osteopontin expression in progressive renal injury in remnant kidney: role of
angiotensin II.
AB - BACKGROUND: Osteopontin (OPN) is a macrophage chemotactic and adhesion molecule
and has been shown to play a role in glomerular and tubulointerstitial injury in
several kidney disease models. METHODS: The present study examined whether OPN
expression is involved in the progression of renal disease following subtotal
(5/6) nephrectomy (STNx) in rats and whether angiotensin II (Ang II) mediates the
up-regulation of renal OPN expression and macrophage accumulation in this model
by administering valsartan, an Ang II type I (AT1) receptor antagonist, or
ramipril, an angiotensin-converting enzyme (ACE) inhibitor. RESULTS: In normal
and sham-operated rat kidneys, OPN was expressed in a few tubules (<5%) and was
absent in glomeruli. Following STNx (weeks 2 to 16), there was substantial up
regulation of OPN mRNA and protein expression in glomeruli [2 to 12
cells/glomerular cross section (gcs)] and tubular epithelial cells (20 to 75%
OPN+). The up-regulation of OPN expression was associated with macrophage
accumulation within the kidney, severe proteinuria, loss of renal function, and
severe histologic damage, including tubulitis and tubulointerstitial fibrosis
(all P < 0.001). Treatment with either valsartan or ramipril completely abrogated
the up-regulation of OPN mRNA and protein expression in glomeruli and tubules.
The reduction in OPN expression was associated with a significant inhibition of
macrophage accumulation and progressive renal injury (P < 0.001). CONCLUSION: An
up-regulation of OPN expression may play a role in progressive renal injury
following STNx. Inhibition of OPN expression may be one of the mechanisms by
which Ang II blockade attenuated renal injury after renal ablation.
PMID- 11012883
TI - Mechanism of chronic obstructive uropathy: increased expression of apoptosis
promoting molecules.
AB - BACKGROUND: We have demonstrated that renal tubular and interstitial cells
undergo pronounced apoptosis during the course of chronic obstructive uropathy
(COU). Apoptosis is a complex cellular process consisting of multiple steps, each
of which is mediated by families of related molecules. These families may include
receptor/ligand molecules such as Fas, Fas ligand, tumor necrosis factor receptor
1 (TNFR-1), and TNF-related apoptosis inducing ligand (TRAIL); signal
transduction adapter molecules such as Fas-associated death domain (FADD), TNFR-1
associated death domain (TRADD), receptor-interacting protein (RIP), Fas
associated factor (FAF), and Fas-associated phosphatase (FAP); or effector
molecules such as caspases. However, the mechanism of tubular cell apoptosis, as
well as the pathogenetic relevance of these apoptosis-related molecules in COU,
remains poorly understood. METHODS: Kidneys were harvested from sham-operated
control mice and mice with COU created by left ureter ligation sacrificed in
groups of three at days 4, 15, 30, and 45. To detect apoptotic tubular and
interstitial cells, in situ end labeling of fragmented DNA was performed. To
detect the expression of apoptosis-related molecules, ribonuclease protection
assay was used with specific antisense RNA probes for Fas, Fas ligand, TNFR-1,
TRAIL, FADD, TRADD, RIP, FAF, FAP, and caspase-8. Immunostaining for Fas, Fas
ligand, TRAIL, TRADD, RIP, and caspase-8 was also performed. To assess the role
of these molecules in COU-associated renal cell apoptosis, the frequencies of
apoptotic tubular and interstitial cells were separately quantitated for each
experimental time point, and their patterns of variation were correlated with
those of apoptosis-related molecules. RESULTS: The obstructed kidneys displayed
increased apoptosis of both tubular and interstitial cells. Tubular cell
apoptosis appeared at day 4 after ureter ligation, peaked (fivefold of control)
at day 15, and decreased gradually until the end of the experiment. In contrast,
interstitial cell apoptosis sustained a progressive increase throughout the
experiment. Apoptosis was minimal at all experimental time points for control and
contralateral kidneys. Compared with control and contralateral kidneys, the
ligated kidneys displayed a dynamic expression of mRNAs for many apoptosis
related molecules, which included an up to threefold increase for Fas, Fas
ligand, TNF-R1, TRAIL, TRADD, RIP, and caspase-8, and an up to twofold increase
for FADD and FAP, but there was little change for FAF. These mRNAs increased
between days 4 and 15, decreased until day 30, but then increased again until day
45. The rise and fall of mRNAs between days 4 and 30 paralleled a similar
fluctuation in tubular cell apoptosis in that period. The subsequent increase of
mRNAs was correlated with a continuous rise of interstitial cell apoptosis. We
demonstrated a positive immunostaining for Fas and Fas ligand in the tubular
cells at early time points as well as in interstitial inflammatory cells at later
time points. Although increased expression of TRAIL, TRADD, RIP, and caspase-8
was noted in tubular cells, there was no staining for these molecules in
interstitial cells. CONCLUSION: The current study documents a dynamic expression
of several molecules that are known to mediate the most crucial steps of
apoptosis. It implicates these molecules in COU-associated renal cell apoptosis
and in the pathogenesis of this condition. It also lays the foundation for
interventional studies, including genetic engineering, to evaluate the molecular
control of apoptosis associated with COU.
PMID- 11012884
TI - Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions
of human diabetic nephropathy.
AB - BACKGROUND: We previously described that monocyte chemoattractant protein-1 (MCP
1) plays an important role in progressive glomerular and interstitial damage in
inflammatory renal diseases. However, the expression of MCP-1 in diabetic
nephropathy remains to be investigated. METHODS: We examined whether locally
expressed MCP-1 participates in human diabetic nephropathy via recruiting and
activating monocytes/macrophages (Mphi). Urinary and serum MCP-1 levels were
measured by enzyme-linked immunosorbent assay in 45 patients with diabetic
nephropathy. The presence of MCP-1 in diseased kidneys was determined by
immunohistochemical and in situ hybridization analyses. RESULTS: Urinary MCP-1
levels were significantly elevated in patients with diabetic nephrotic syndrome
and advanced tubulointerstitial lesions. Moreover, urinary levels of MCP-1 were
well correlated with the number of CD68-positive infiltrating cells in the
interstitium. In contrast, serum MCP-1 levels remained similar to those of
healthy volunteers. Furthermore, we detected the MCP-1-positive cells in the
interstitium of diabetic nephropathy via both immunohistochemical and in situ
hybridization analyses. CONCLUSION: These observations suggest that locally
produced MCP-1 may be involved in the development of advanced diabetic
nephropathy, especially in the formation of tubulointerstitial lesions possibly
through Mphi recruitment and activation. Moreover, up-regulation of MCP-1 may be
a common pathway involved in the progressive tubulointerstitial damage in
diabetic nephropathy as well as inflammatory renal diseases.
PMID- 11012885
TI - Microsphere-adenoviral complexes target and transduce the glomerulus in vivo.
AB - BACKGROUND: Developing new treatments for glomerulonephritis makes the glomerulus
a logical target for gene therapy. Microspheres may lodge in the glomerulus, and
replication-deficient recombinant adenoviruses are potent mediators of gene
transfer. We postulated that adenoviral-microsphere complexes could result in DNA
transfer (transduction) into glomerular cells in vivo. METHODS: Two adenoviruses,
each one containing a luciferase or beta-galactosidase (beta-gal) transgene
expression cassette, were complexed to polystyrene microspheres. To assess in
vivo glomerular transduction with this tool, male Sprague-Dawley rats underwent
aortic injections with adenovirus linked to 11 or 16 microm diameter
microspheres. RESULTS: After 48 hours, adenoviral-microsphere complexes resulted
in transduction of up to 19% of glomeruli per kidney section. Endothelial and
mesangial cells were transduced with this approach, and transprotein expression
persisted for 21 days. Transduction efficiency was greater in the 16 microm
group. For all rats, there was a strong correlation between kidney luciferase
levels and the number of beta-gal-positive glomeruli (r = 0.87), indicating that
transgene expression was primarily glomerular in location. This was supported by
reverse transcriptase in situ polymerase chain reaction, which demonstrated
glomerular localization of the beta-gal transgene. CONCLUSIONS: The aortic
injection of adenoviral-microsphere complexes transduces the glomerulus in vivo
and may be a useful tool in developing approaches to gene therapy of glomerular
disease.
PMID- 11012886
TI - Hepatocyte growth factor induces branching tubulogenesis in MDCK cells by
modulating the activin-follistatin system.
AB - BACKGROUND: The activin-follistatin system is expressed in tubular cells of the
kidney. The present study was conducted to examine the role of the activin
follistatin system in tubulogenesis using Madin-Darby canine kidney (MDCK) cells
as a model system. METHODS: Tubulogenesis was assessed using MDCK cells cultured
in collagen gel. The effect of recombinant human activin A on tubulogenesis was
examined. Blockade of the action of endogenous activin was achieved by either
adding follistatin or transfection of dominant-negative mutant of the type II
activin receptor. The production of activin A was examined by Northern blotting,
in situ hybridization, and Western blotting. RESULTS: MDCK cells expressed mRNA
for the betaA subunit of activin. These cells formed spherical cysts when
cultured in collagen gel. Hepatocyte growth factor (HGF) added to the spherical
cysts induced branching tubulogenesis. When activin A was added together with
HGF, activin A blocked the branching tubulogenesis induced by HGF, and the
activin-treated cells were scattered. Conversely, follistatin, an antagonist of
activin A, induced branching tubulogenesis qualitatively similar to that induced
by HGF. Adenovirus vector-mediated transfer of the gene encoding truncated type
II activin receptor, which acts as a dominant negative mutant, also induced
branching tubulogenesis. Finally, HGF markedly inhibited the production of
activin A in MDCK cells cultured in collagen gel. CONCLUSION: Activin A produced
in MDCK cells tonically inhibits branching tubulogenesis, and HGF induced
branching tubulogenesis mainly by blocking the production of activin A.
PMID- 11012887
TI - Cubilin- and megalin-mediated uptake of albumin in cultured proximal tubule cells
of opossum kidney.
AB - BACKGROUND: Reabsorption of albumin from the glomerular filtrate occurs via
receptor-mediated endocytosis in the proximal tubule. This process is initiated
by binding of albumin in apical clathrin-coated pits, followed by endocytosis and
degradation in lysosomes. Although binding sites have been characterized by
kinetic studies, the receptors responsible for the binding of albumin have not
been fully identified. Two giant glycoproteins, cubilin and megalin, constitute
important endocytic receptors localized to the kidney proximal tubule. METHODS:
In the present study, we examined the colocalization of cubilin and megalin in
the endocytic pathway and the relationship between the uptake of albumin and the
expression of cubilin and megalin in opossum kidney (OK) proximal tubule cells by
immunocytochemistry and immunoblotting. RESULTS: OK cells expressed both cubilin
and megalin. The light microscope labeling patterns for cubilin and megalin were
almost identical and were mainly located at the surface area of the cells.
Cubilin and megalin were also shown to colocalize on cell surface microvilli, in
coated pits, and in endocytic compartments at the electron microscope level.
Endocytosed bovine serum albumin (BSA) was identified exclusively in cells
expressing megalin and cubilin. Uptake of BSA-FITC was saturable and inhibited by
receptor-associated protein (RAP) and by intrinsic factor-vitamin B12 complex (IF
B12) at high concentrations. Significant inhibition was also observed by specific
antibodies to cubilin, and megalin and cubilin antisense oligonucleotides
likewise significantly reduced albumin uptake. Egg albumin did not affect the
uptake of BSA. CONCLUSION: The present observations suggest that the two
receptors cubilin and megalin are both involved in the endocytic uptake of
albumin in renal proximal tubule cells.
PMID- 11012888
TI - Diabetes mellitus increases endothelin-1 gene transcription in rat kidney.
AB - BACKGROUND: Mesangial cell hypertrophy and increased extracellular matrix (ECM)
contribute to mesangial expansion in early progressive diabetic nephropathy.
Previous studies suggest that the growth factor endothelin-1 (ET-1) is not only
up-regulated in diabetes, but may mediate the effects of hyperglycemia on
mesangial cell hypertrophy and ECM synthesis. In models of diabetes mellitus, the
mechanisms underlying increased ET-1 peptide and mRNA remain unknown. Therefore,
our purpose is to determine whether ET-1 gene activity increases in kidneys of
streptozotocin (SZT)-treated rats. METHODS: Male Sprague-Dawley rats were
injected with either SZT or vehicle. Parameters including glucose, body weight,
24-hour urine volume, urinary protein, and urinary ET-1 excretion were recorded.
All rats were sacrificed at 12 weeks postinjection. Prepro-ET-1 mRNA from whole
kidneys was determined using both RNase protection and reverse transcription
polymerase chain reaction (RT-PCR). The abundance of ET-1 peptide in primary
cultured mesangial cells was detected by indirect immunofluorescence following
treatment with 5.6, 11.2, or 22.5 mmol/L D-glucose for 24 hours. Cellular ET-1
mRNA was measured using RT-PCR in control cells at time 0 and also following
exposure to increasing concentrations of glucose for 24 hours. Rat mesangial
cells were transfected with a luciferase reporter construct containing the rat ET
1 promoter (pET1. Luc), and relative ET-1 promoter activity was measured after a
24-hour exposure to 5.6 and 22.5 mmol/L of D- or L-glucose. RESULTS: After 12
weeks of hyperglycemia, diabetic rats gained less weight (344 +/- 23.9 vs. 548.75
+/- 15.08 g), had increased urinary volume (158.6 +/- 24.32 vs. 8.38 +/- 1.56
mL/day), and had marked proteinuria (101.7 +/- 12.2 vs. 14.1 +/- 2.8 mg/day)
compared with controls. Total urinary ET-1 peptide increased 26.4-fold in
diabetic versus control rats (17.5083 +/- 5.405 vs. 0.6635 +/- 0.343 ng/day). ET
1 mRNA extracted from whole rat kidneys was increased 2.1-fold in diabetic versus
control animals. Primary cultured rat mesangial cells demonstrated a significant
increase in immunofluorescence labeling of ET-1 peptide and ET-1 mRNA in response
to increasing concentrations of glucose. Furthermore, transfected mesangial cells
exposed to 22.5 mmol/L D-glucose showed a 1.6-fold increase in ET-1 promoter
activity relative to those treated with 5.6 mmol/L glucose. CONCLUSION: Glucose
increases ET-1 gene expression in the kidney of the SZT-treated rat model of
diabetes mellitus. Furthermore, high glucose induces ET-1 expression in primary
cultured rat mesangial cells and directly enhances ET-1 promoter activity. The
greater relative increase in peptide compared with transcription suggests the
potential participation of other mechanisms such as increased mRNA stability,
protein stability, and/or enhanced translational efficiency.
PMID- 11012889
TI - The Duffy antigen receptor for chemokines is up-regulated during acute renal
transplant rejection and crescentic glomerulonephritis.
AB - BACKGROUND: Recruitment of leukocytes during immune responses requires the
coordinate expression of adhesion molecules in concert with chemokines and their
receptors. The Duffy antigen receptor for chemokines (DARC) binds multiple
chemokines and is expressed on postcapillary venules in the normal kidney. The
chemokine receptor CCR5, which shares the ligand regulated upon activation,
normal T-cell expressed and secreted (RANTES) with DARC, is expressed by
infiltrating T cells in the renal interstitium. As DARC might be involved in the
attraction of CCR5-positive cells, we studied the distribution of DARC and CCR5
in two forms of cell-mediated renal injury: renal allograft rejection and
crescentic glomerulonephritis (cGN). METHODS: A total of 87 renal specimens,
including 12 pretransplant biopsies, 47 transplant biopsies (Banff 1, N = 10;
Banff 2, N = 19; and various other lesions N = 18), and 28 biopsies from patients
with cGN, was analyzed. Immunohistochemistry for CCR5 and DARC was performed on
serial sections of formalin-fixed and paraffin-embedded tissue. RESULTS: Compared
with pretransplant biopsies, the mean number of DARC-positive interstitial
venules was significantly increased during both transplant rejection and cGN.
This was accompanied by an infiltration of CCR5-positive leukocytes. During
transplant rejection, the number and distribution of CCR5-positive cells
correlated with DARC-positive venules. Infiltrating CCR5-positive leukocytes were
found mainly in the interstitium, often clustering around Bowman's capsules in
biopsies from cGN. The number of glomerular CCR5 positive cells is low, but they
are common in a subset of crescents. CONCLUSIONS: We hypothesize that the
increased number of DARC-positive venules in areas of interstitial injury and the
colocalization with CCR5-positive infiltrating leukocytes may indicate a role for
endothelial DARC expression during leukocyte adhesion and interstitial
infiltration.
PMID- 11012890
TI - Small proteoglycans of normal adult human kidney: distinct expression patterns of
decorin, biglycan, fibromodulin, and lumican.
AB - BACKGROUND: Among the members of the small leucine-rich proteoglycan family,
decorin, biglycan, and fibromodulin have been proposed to be potent modulators of
transforming growth factor-beta (TGF-beta) activity, thereby playing an important
role in the pathogenesis of fibrotic kidney diseases. Furthermore, decorin
expression influences the expression of p21WAF1/CIP1, which has been related to
kidney hypertrophy and hyperplasia. However, none of the members of this
proteoglycan family have been investigated in normal adult human kidney cortex,
thus making it impossible to correlate disease-mediated alterations of their
expression with the normal situation in vivo. METHODS: The chondroitin/dermatan
sulfate proteoglycans, decorin and biglycan, and the keratan sulfate
proteoglycans, fibromodulin and lumican, were investigated in normal human adult
renal cortex by immunohistochemistry on the light and electron microscopic level
and by in situ hybridization. Northern blot and reverse transcription-polymerase
chain reaction (RT-PCR) methods were used to get an estimate of their expression
in isolated glomeruli. Decorin excretion with the urine was measured by Western
blotting. RESULTS: Two bands of decorin and a single band of biglycan mRNA were
identified in Northern blots of isolated glomeruli. Amplification by RT-PCR was
required to detect the signals for fibromodulin and lumican. All four
proteoglycans were preferentially expressed in the renal interstitium with
accumulations around tubules. Weak expression was found in the mesangial matrix.
Biglycan was expressed by glomerular endothelial cells and, together with
fibromodulin, was synthesized and deposited in distal tubular cells and
collecting ducts. Immunogold labeling indicated the presence of the proteoglycans
in the glomerular basement membrane, which was interpreted as a result of
glomerular filtration. Indirect evidence suggested tubular reuptake of decorin
after glomerular filtration. CONCLUSION: The data indicate that the different
cells of the adult human kidney are characterized by a distinct expression
pattern of the four small proteoglycans. It is suggested that these proteoglycans
may have distinct pathophysiological roles depending upon whether they are
expressed by mesangial cells, endothelial cells, epithelial cells, or cells of
the tubulointerstitium.
PMID- 11012891
TI - CD59 protects rat kidney from complement mediated injury in collaboration with
crry.
AB - BACKGROUND: As previously reported, the membrane-bound complement regulator at
the C3 level (Crry/p65) is important in maintaining normal integrity of the
kidney in rats. However, the role of a complement regulator at the C8/9 level
(CD59) is not clear, especially when activation of complement occurs at the C3
level. The aim of this work was to elucidate the in vivo role of CD59 under C3
activating conditions. METHODS: Two monoclonal antibodies, 5I2 and 6D1, were used
to suppress the function of Crry and CD59, respectively. In order to activate
alternative the pathway of complement, the left kidney was perfused with 5I2
and/or 6D1 and was recirculated. RESULTS: In the kidneys perfused with 5I2 alone,
deposition of C3 and membrane attack complex (MAC) was observed in the
peritubular capillaries, vasa recta, and tubular basement membranes. Cast
formation, tubular dilation and degeneration, and cellular infiltration were
observed at days 1 and 4, and they recovered by day 7. Further suppression of
CD59 by 6D1 significantly enhanced the deposition of MAC and worsened the already
exacerbated tubulointerstitial injury. These effects of 6D1 were dose dependent.
Perfusion with 6D1 alone did not induce histologic damage or MAC deposition in
the tubulointerstitium. CONCLUSIONS: In rats, CD59 maintains normal integrity of
the kidney in collaboration with Crry in rats against complement-mediated damage
in vivo.
PMID- 11012892
TI - Complement is activated in kidney by endotoxin but does not cause the ensuing
acute renal failure.
AB - BACKGROUND: Acute renal failure (ARF) in sepsis occurs when the release of
multiple inflammatory mediators is induced by bacterial endotoxins. C3 mRNA is
markedly up-regulated in mouse kidney after exposure to lipopolysaccharide (LPS).
We hypothesized that LPS could induce tubular synthesis and secretion of C3,
leading to activation of the complement cascade and direct renal tubular injury.
METHODS: ARF was induced in mice by intravenous injection of LPS and was
confirmed by an acute rise in blood urea nitrogen (BUN) and histologically by
acute tubular necrosis. Three separate strategies were used to investigate the
role of the complement system in this model of ARF: (1) Crry-Ig, a recombinant
protein containing the potent murine complement C3 activation inhibitor Crry was
injected at the same time as LPS (N = 8). (2) LPS was injected into transgenic
mice overexpressing Crry in glomeruli and tubules (N = 8), and (3) LPS was
injected into C3-deficient mice (N = 5). RESULTS: Compared with unmanipulated
mice, C3 staining by immunofluorescence (IF) microscopy in mice injected with LPS
was greater in renal cortical tubular cells (IF score of 2. 1 +/- 0.1 vs. 1.4 +/-
0.2 in controls, P = 0.013), most prominently at the basolateral surface. LPS
injection led to a 16- to 42-fold increase in urinary C3 excretion. Despite
reduction or complete elimination of renal C3 with maneuvers suppressing
complement activation, BUN values were not statistically different across all
groups. In no experiment did BUN values correlate with the extent of C3 staining.
CONCLUSION: Although LPS up-regulates renal C3 synthesis, resulting in
basolateral tubular C3 deposition, this is not responsible for LPS-induced ARF in
mice.
PMID- 11012893
TI - Elastic fiber proteins in the glomerular mesangium in vivo and in cell culture.
AB - BACKGROUND: Glomerular capillaries of the mammalian kidney are exposed to high
intraluminal hydrostatic pressures and require elastic constraint to maintain
size, shape, and integrity. Previous morphological and functional studies
indicated that the extracellular matrices of glomeruli, that is, basement
membrane and mesangial matrix, contribute to glomerular resilience and mechanical
stability. Immunofluorescence microscopy findings demonstrated elastic fiber
components to be located in the renal vasculature, including glomeruli. The aim
of this study was to clarify the exact glomerular localization, composition, and
cellular production of these proteins. METHODS: We examined the renal
distribution of the elastic fiber proteins fibrillin-1, emilin, microfibril
associated glycoproteins (MAGPs) 1 and 2, latent transforming growth factor
binding protein-1 (LTBP-1), and elastin using immunohistology and immunoelectron
microscopy of human, rat, and mouse kidneys. In mesangial cell cultures, we also
studied the expression and extracellular deposition of such proteins by use of
Northern blotting and immunocytochemistry. RESULTS: Fibrillin-1, emilin, MAGPs 1
and 2, and LTBP-1 were present in glomeruli of mouse, rat, and human kidney,
where they were located predominantly in the mesangial extracellular matrix
underlying glomerular endothelium and basement membrane. Several of these
proteins, as well as elastin, were also expressed in the renal vasculature. While
elastin localized to the glomerular vascular pole in afferent and efferent
arterioles extending to Bowman's capsule, it was not found in the glomerular
capillary tuft. Cultured mesangial cells of rat, mouse, and human kidneys
expressed mRNAs of fibrillin-1, emilin, MAGP-2, and elastin, and the respective
proteins localized within and outside of mesangial cells, as shown by
immunocytochemistry. mRNA expression of fibrillin-1, emilin, and elastin was
strong in quiescent mesangial cells; their gene expression was further up
regulated by transforming growth factor-beta1, while it was transiently reduced
when cells were exposed to mitogenic 10% fetal calf serum and platelet-derived
growth factor. CONCLUSIONS: These findings demonstrate that specific elastic
fiber proteins are produced and secreted by mesangial cells. This process is
regulated by growth factors. Their abundance in the extracellular matrix of the
mesangium is in keeping with the concept that elastic fiber proteins contribute
to the mechanical stability and elastic strength of the glomerular capillary
tuft.
PMID- 11012894
TI - Expression of DNA topoisomerases in chronic proliferative kidney disease.
AB - BACKGROUND: Circulating autoantibodies to human topoisomerases have been reported
in glomerular kidney disease associated with scleroderma and systemic lupus
erythematosus. However, limited information is available about the expression of
topoisomerases in the kidney under normal and pathological conditions. METHODS:
The expression of DNA topoisomerases I and IIalpha was studied by
immunohistochemistry on archival biopsies from 70 patients with chronic renal
diseases. Normal kidney tissue was examined for comparison. Topoisomerase I was
detected by means of monoclonal antibody (mAb) C21, and topoisomerase IIalpha was
detected by means of mAb Ki-S4. In addition, mAb Ki-M1p was used to assess the
density of monocytic infiltrates. All parameters were assessed in a
semiquantitative manner. RESULTS: Glomerular topoisomerase IIalpha levels were
increased in mesangial proliferative glomerulonephritis (MPGN), rapidly
progressive glomerulonephritis (RPGN), and lupus nephritis (LN) and were reduced
in membranous glomerulonephritis (MGN), chronic transplant nephropathy (CTN), and
tubulointerstitial nephritis (TIN). Tubular epithelia displayed high
topoisomerase IIalpha levels in mesangiocapillary glomerulonephritis (MCGN),
RPGN, TIN, miscellaneous entities (MISC) and LN, and displayed low levels in MPGN
and CTN. Topoisomerase I expression was high in the glomeruli of focal segmental
glomerulosclerosis (FSGS), MCGN, and RPGN and was extreme in LN, whereas it was
strikingly diminished in the glomeruli of MGN, CTN, and TIN. Almost all
conditions displayed lower tubular topoisomerase I levels than normal kidney,
except for LN, in which the enzyme content was markedly increased. Increased
glomerular monocytic infiltrates were found in FSGS, MCGN, RPGN, TIN, and LN, and
tubulointerstitial Ki-M1p+ cells were seen at high numbers in MCGN, RPGN, TIN,
MISC, and LN. The expression of the topoisomerases I and IIalpha was
significantly correlated; also, topoisomerases showed a positive association with
the density of monocytic infiltrates. The parameter profiles exhibited
significant differences between distinct types of chronic renal disease.
CONCLUSION: Topoisomerase IIalpha expression is tightly linked to cell cycling,
and topoisomerase I is likely a reflection of gene transcription. Rapidly
progressing glomerular disease therefore appears to be accompanied by active
mesangial cell proliferation and increased metabolic activity in glomerular
cells. The correlation with inflammatory infiltrates is likely to reflect a
positive feedback mechanism involving cytokines, growth factors, and adhesion
molecules. Assessment of topoisomerases may therefore be of diagnostic help and
might allow prognostic predictions. Provided that our observations are supported
by clinicopathological follow-up studies, one might envisage the use of
topoisomerase inhibitors in the therapy of chronic proliferative renal disease
refractory to current treatment protocols.
PMID- 11012895
TI - Binding properties of a selective tritiated vasopressin V2 receptor antagonist,
[H]-SR 121463.
AB - BACKGROUND: [3H]-SR 121463 is the first radiolabeled selective nonpeptide
vasopressin V2 receptor antagonist ligand that has been reported to date. In the
present work, we studied the binding properties of [3H]-SR 121463 for renal V2
receptors from animal and human origins. METHODS: Binding studies were performed
with [3H]-SR 121463 in Chinese hamster ovary (CHO) cells transfected with the
human V2 receptor and in various kidney preparations expressing the native V2
receptors (rat, rabbit, dog, pig, monkey, and human). Autoradiographies were
performed in rat and human kidney sections. RESULTS: [3H]-SR 121463 binding to
CHO cells stably transfected with the cloned human renal V2 receptor was
specific, highly stable, time dependent, saturable, and reversible. A single
population of high-affinity binding sites was identified (Kd = 0.94 +/- 0.34
nmol/L, Bmax = 9876 +/- 317 fmol/mg protein). Of note, [3H]-SR 121463 revealed a
higher number (about 40%) of V2 sites than [3H]-AVP in the same preparation.
Displacement of [3H]-SR 121463 binding by reference peptide and nonpeptide
vasopressin/oxytocin compounds exhibited a typical AVP V2 profile. [3H]-SR 121463
also displayed a high affinity for native V2 receptors in several kidney
preparations from rat, pig, dog, rabbit, bovine, monkey, and human. The
autoradiographic experiments using rat and human kidney sections showed intense
labeling in the medullopapillary region and lower intensity in the cortex,
consistent with a main localization of V2 receptors on collecting tubules.
CONCLUSION: [3H]-SR 121463 is a useful ligand for the specific labeling of animal
and human V2 receptors and could be a suitable probe for the search and in situ
localization of V2 sites.
PMID- 11012896
TI - Chronic effect of parathyroid hormone on NHE3 expression in rat renal proximal
tubules.
AB - BACKGROUND: The most abundant Na+/H+ exchanger in the apical membrane of proximal
tubules is the type 3 isoform (NHE3), and its activity is acutely inhibited by
parathyroid hormone (PTH). In the present study, we investigate whether changes
in protein abundance as well as in mRNA levels play a significant role in the
long-term modulation of NHE3 by PTH. METHODS: Three groups of animals were
compared: (1) HP: animals submitted to hyperparathyroidism by subcutaneous
implantation of PTH pellets, providing threefold basal levels of this hormone
(2.1 U. h-1); (2) control: sham-operated rats in which placebo pellets were
implanted; (3) PTX: animals submitted to hypoparathyroidism by
thyroparathyroidectomy followed by subcutaneous implantation of thyroxin pellets,
which provided basal levels of thyroid hormone. After eight days, we measured
bicarbonate reabsorption in renal proximal tubules by in vivo microperfusion.
NHE3 activity was also measured in brush border membrane (BBM) vesicles by proton
dependent uptake of 22Na. NHE3 expression was evaluated by Northern blot, Western
blot and immunohistochemistry. RESULTS: Bicarbonate reabsorption in renal
proximal tubules was significantly decreased in HP rats. Na+/H+ exchange activity
in isolated BBM vesicles was 6400 +/- 840, 9225 +/- 505, and 12205 +/- 690 cpm.
mg-1. 15 s-1 in HP, sham, and PTX groups, respectively. BBM NHE3 protein
abundance decreased 39.3 +/- 8.2% in HP rats and increased 54.6 +/- 7.8% in PTX
rats. Immunohistochemistry showed that expression of NHE3 protein in apical BBM
was decreased in HP rats and was increased in PTX rats. Northern blot analysis of
total kidney RNA showed that the abundance of NHE3 mRNA was 20.3 +/- 1.3%
decreased in HP rats and 27. 7 +/- 2.1% increased in PTX. CONCLUSIONS: Our
results indicate that the chronic inhibitory effect of PTH on the renal proximal
tubule NHE3 is associated with changes in the expression of NHE3 mRNA levels and
protein abundance.
PMID- 11012897
TI - Microcomputed tomography of kidneys following chronic bile duct ligation.
AB - BACKGROUND: In hepatic cirrhosis, renal sodium and water retention can occur
prior to decreases in renal blood flow (RBF). This may be explained in part by
redistribution of the intrarenal microcirculation toward the juxtamedullary
nephrons. To appreciate this three-dimensional spatial redistribution better, we
examined the intrarenal microcirculatory changes using microcomputed tomography
(micro-CT) in rats subjected to chronic bile duct ligation (CBDL). METHODS: Six
kidneys from control rats and eight kidneys from rats that had undergone CBDL for
21 days were perfusion fixed in situ at physiological pressure, perfused with
silicon-based Microfil containing lead chromate, embedded in plastic, and scanned
by micro-CT. The microvasculature in the reconstructed three-dimensional renal
images was studied using computerized image-analysis techniques. To determine the
physiological condition of the rats, parallel experiments were conducted on six
control and six CBDL rats to measure mean arterial pressure (MAP), RBF,
glomerular filtration rate (GFR), urine flow (UF) rate, and sodium excretion by
conventional methods. RESULTS: The percentage of vasculature in the renal cortex
from CBDL rats was significantly decreased (10.8 +/- 0.4% vs. 16.8 +/- 2.7%
control values). However, the vascular volume fractions of the medullary tissues
were not significantly altered. There were no significant differences in the
number of glomeruli between groups (36,430 +/- 1908 CBDLs, 36,609 +/- 3167
controls). The CBDL rats had a similar GFR than the controls but a reduced MAP,
RBF, UF, and sodium excretion. CONCLUSIONS: The results indicate that after CBDL,
there is a selective decrease in cortical vascular filling, which may contribute
to the salt and water retention that accompanies cirrhosis.
PMID- 11012898
TI - H+-ATPase activity on unilateral ureteral obstruction: interaction of endogenous
nitric oxide and angiotensin II.
AB - BACKGROUND: A number of cytokines, vasoactive compounds, chemoattractant
molecules, and growth factors are up-regulated in obstruction. Following the
onset of ureteral obstruction, angiotensin II production is rapidly stimulated.
Cytokine-induced expression of inducible nitric oxide synthase (iNOS) has been
reported in primary cultures of inner medullary collecting duct (IMCD) cells. We
found that the defective urinary acidification in unilateral ureteral obstruction
(UUO) includes an intensive decrease in bafilomycin-sensitive H+-ATPase activity
in microdissected IMCD segments. METHODS: To investigate the interaction between
endogenous nitric oxide and angiotensin II on H+-ATPase activity, we used
microdissected IMCD segments of unilaterally obstructed, contralateral, and
control kidneys to measure the bafilomycin-sensitive ATPase activity and nitric
oxide synthase (NOS) activity. The generated NO was also evaluated. RESULTS:
Preincubation of obstructed IMCD segments in the presence of a competitive
inhibitor of NOS, NG-nitro-L-arginine methyl ester (L-NAME) 1 mmol/L, and in the
presence of a specific inhibitor of calcium/calmodulin-independent NOS (iNOS),
aminoguanidine 1 mmol/L, each for 60 minutes, significantly increased bafilomycin
sensitive H+-ATPase. A greater increase on iNOS activity (fmol [3H]
citrulline/min/microg protein) and a lesser increase in calcium/calmodulin
dependent NOS activity (cNOS) were observed in the obstructed renal medulla. This
inhibitory effect of obstruction was abolished when IMCDs were incubated with 10
5 to 10-8 mol/L losartan. Decreasing doses of the angiotensin II type 1 (AT1)
receptor inhibitor caused an increase in bafilomycin-sensitive H+-ATPase, with a
maximum increase at 10-8 mol/L losartan. A decrease on iNOS activity was
demonstrated in the obstructed renal medulla incubated with losartan in
concentrations of 10-5 to 10-8 mol/L, the same losartan concentrations that
showed recovery of vacuolar H+-ATPase activity. Similarly, a decrease on the
generation of NO after incubation with losartan 10-5 to 10-8 mol/L was shown.
CONCLUSION: From these results, we suggest that endogenous NO increased by iNOS
is involved in the inhibition of H+-ATPase activity in obstructed IMCD segments.
The recovery of H+-ATPase activity in IMCD of obstructed kidneys induced by
losartan may be related to a decrease of inducible NOS activity.
PMID- 11012899
TI - Cyclosporine stimulates Na+-K+-Cl- cotransport activity in cultured mouse
medullary thick ascending limb cells.
AB - BACKGROUND: Cyclosporine (CsA) has been shown to alter the activity of plasma
membrane transporters in kidney epithelial cells. In this study, we have
investigated the effects of CsA on Na+,K+-ATPase and Na+-K+-Cl- cotransport
activities in cultured cells derived from microdissected mouse medullary thick
ascending limb (mTAL) cells. METHODS: Experiments were carried out on subcultured
confluent mouse TAL cells. Reverse transcription-polymerase chain reaction
experiments showed that they expressed the mNKCC2 electroneutral Na+-K+-Cl-
cotransporter and ROM-K1 and ROMK2 potassium channel mRNA. Western blotting also
revealed the presence of the 40 kD ROMK protein using an anti-ROMK antibody. The
effect of CsA (100 ng/mL) on ion transport was assessed by measuring the influx
and efflux of rubidium (86Rb+) and 36Cl-, used as tracers of K+ and Cl-
movements, on cells grown on Petri dishes or permeable filters. RESULTS: CsA
inhibited by 38% the ouabain-sensitive component of 86Rb+ influx mediated by the
Na+,K+-ATPase pumps. CsA also increased by 38% the ouabain-resistant furosemide
sensitive component (Or-Fs) of 86Rb+ influx, reflecting the Na+-K+-Cl-
cotransport activity and stimulated the basolateral efflux of 36Cl- from mTAL
cells grown on filters. The CsA-stimulated basal efflux of Cl- was prevented by
the basal addition of the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)
benzoate (NPPB, 10-4 mol/L). Apical addition of the K+ channel blocking agent
Ba2+ (10-4 mol/L) partially prevented the CsA-stimulated basal efflux of Cl-.
Adding Ba2+ to the luminal side of cells grown on Petri dishes also prevented the
rise in apical 86Rb+ efflux and the increased Or-Fs component of 86Rb+ influx
caused by CsA. CONCLUSION: These results indicated that CsA may stimulate the Na+
K+-Cl- cotransport activity and also suggested that this immunosuppressive agent
may interfere in the recycling of apical K+ in this model of cultured mouse TAL
cells.
PMID- 11012900
TI - Proinflammatory gene expression and macrophage recruitment in the rat remnant
kidney.
AB - BACKGROUND: Macrophage (Mphi) infiltration may contribute to chronic renal
injury. We therefore sought to examine the expression of genes associated with
Mphi recruitment in the rat remnant kidney model. METHODS: Male Munich Wistar
rats underwent 5/6 nephrectomy or sham operation (SHM, N = 18) and received no
treatment (VEH, N = 18), enalapril 100 mg/L (ENA, N = 18), or candesartan 70 mg/L
(CSN, N = 24) in drinking water. Competitive, quantitative reverse transcription
polymerase chain reaction was used to determine renal cortex mRNA levels for cell
adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular
adhesion molecule-1 (ICAM-1), the Mphi chemoattractant monocyte chemoattractant
protein-1 (MCP-1), Mphi products interleukin-1beta (IL-1beta) and tumor necrosis
factor-alpha (TNF-alpha), and the profibrotic cytokine transforming growth factor
beta1 (TGF-beta1), at intervals post-nephrectomy. RESULTS: Glomerular and
interstitial Mphi infiltration in VEH rats was associated with an early (4 week)
and sustained rise in MCP-1 and TGF-beta1 mRNA levels. Progressive increases in
ICAM-1, VCAM-1, IL-1beta, and TNF-alpha expression followed at 8 and 12 weeks.
Immunostaining in VEH rats localized TGF-beta1 to glomeruli, tubules, and
interstitium; MCP-1 to tubules and interstitial cells; ICAM-1 to glomeruli; and
IL-1beta and TNF-alpha to tubules and interstitial cells. At 12 weeks, both
treatments normalized systolic blood pressure (ENA, 105 +/- 6; CSN, 97 +/- 3 mm
Hg) and the urinary protein excretion rate (ENA, 8.4 +/- 0.9; CSN, 5.7 +/- 0.8
mg/day), prevented renal injury (focal and segmental glomerulosclerosis: ENA, 3.3
+/- 0.9; CSN, 1.3 +/- 0.4%), and suppressed Mphi infiltration and cytokine
expression (with the exception of TNF-alpha) to near SHM levels. CONCLUSIONS:
These findings support the hypothesis that the coordinated up-regulation of
several molecules regulating Mphi recruitment and activation is a fundamental
response to renal mass ablation and is dependent on an intact renin-angiotensin
system. We speculate that these responses may play a role in the pathogenesis of
the ensuing glomerulosclerosis and tubulointerstitial fibrosis.
PMID- 11012901
TI - Effects of diabetes and hypertension on glomerular transforming growth factor
beta receptor expression.
AB - BACKGROUND: Several studies have suggested that transforming growth factor-beta1
(TGF-beta1) is an important determinant of diabetic glomerular injury. TGF-beta1
forms a heteromeric complex with two cellular receptor subtypes, designated TGF
beta RII and TGF-beta RI, but the effects of diabetes mellitus on glomerular TGF
beta receptor expression have not been completely elucidated. We first compared
the effect of experimental type I diabetes mellitus and uninephrectomy on
glomerular TGF-beta receptor expression in spontaneously hypertensive rats
(SHRs), and then sought to determine whether changes in TGF-beta receptor
expression were strain specific by studying normotensive Wistar-Kyoto (WKY) rats.
METHODS: Five groups of male SHRs were studied. The first group received
streptozotocin (60 mg/kg IV) and was studied after one week. The second group
received streptozotocin and was studied after two weeks. The third group received
streptozotocin (60 mg/kg IV) but received insulin to maintain euglycemia. The
fourth group of age-matched SHRs served as the control group, while a fifth group
of SHRs underwent uninephrectomy. Four groups of male WKY rats were also studied.
The first group of WKY rats served as the age-matched control group. The second
group of WKY rats received streptozotocin, while a third group of WKY rats
underwent uninephrectomy. The fourth group underwent uninephrectomy and received
streptozotocin. At each time point, glomeruli were isolated for protein
extraction, and the protein was subjected to Western blot analysis of TGF-beta
RII and TGF-beta RI expression. RESULTS: Basal expression of both TGF-beta
receptors per microgram of glomerular protein was similar in normotensive WKY
rats and hypertensive SHRs. Hyperglycemia (blood glucose level, 17.8 +/- 2.9
mmol/L) led to an early twofold increase in TGF-beta RII protein expression and a
fourfold increase in TGF-beta RI protein expression in the glomeruli of
hypertensive diabetic SHRs compared with euglycemic SHRs (blood glucose level,
5.8 +/- 0.8 mmol/L), which was sustained after two weeks. Insulin treatment
(blood glucose level, 5. 2 +/- 0.9 mmol/L) normalized both TGF-beta RII and TGF
beta RI expression in the glomeruli of SHRs that received streptozotocin.
Glomerular capillary hypertension in the uninephrectomized SHRs led to a twofold
increase in glomerular TGF-beta RII protein expression, but did not reproduce the
effect of diabetes mellitus on TGF-beta RI expression. In contrast to the
findings in SHRs, neither hyperglycemia (blood glucose level, 15.5 +/- 2.1
mmol/L), uninephrectomy, nor hyperglycemia (blood glucose level, 16.8 +/- 3.0
mmol/L) and uninephrectomy altered TGF-beta receptor expression in the glomeruli
of normotensive WKY rats. CONCLUSION: These studies support the hypothesis that
hemodynamic factors and metabolic factors influence glomerular TGF-beta receptor
in vivo in the SHRs.
PMID- 11012902
TI - Ryanodine receptor and capacitative Ca2+ entry in fresh preglomerular vascular
smooth muscle cells.
AB - BACKGROUND: A multiplicity of hormonal, neural, and paracrine factors regulates
preglomerular arterial tone by stimulating calcium entry or mobilization. We have
previously provided evidence for capacitative (store-operated) Ca2+ entry in
fresh renal vascular smooth muscle cells (VSMCs). Ryanodine-sensitive receptors
(RyRs) have recently been identified in a variety of nonrenal vascular beds.
METHODS: We isolated fresh rat preglomerular VSMCs with a magnetized
microsphere/sieving technique; cytosolic Ca2+ ([Ca2+]i) was measured with fura-2
ratiometric fluorescence. RESULTS: Ryanodine (3 micromol/L) increased [Ca2+]i
from 79 to 138 nmol/L (P = 0.01). Nifedipine (Nif), given before or after
ryanodine, was without effect. The addition of calcium (1 mmol/L) to VSMCs in
calcium-free buffer did not alter resting [Ca2+]i. In Ca-free buffer containing
Nif, [Ca2+]i rose from 61 to 88 nmol/L after the addition of the Ca2+-ATPase
inhibitor cyclopiazonic acid and to 159 nmol/L after the addition of Ca2+ (1
mmol/L). Mn2+ quenched the Ca/fura signal, confirming divalent cation entry. In
Ca-free buffer with Nif, [Ca2+]i increased from 80 to 94 nmol/L with the addition
of ryanodine and further to 166 nmol/L after the addition of Ca2+ (1 mmol/L).
Mn2+ quenching was again shown. Thus, emptying of the sarcoplasmic reticulum (SR)
with ryanodine stimulated capacitative Ca2+ entry. CONCLUSION: Preglomerular
VSMCs have functional RyR, and a capacitative (store-operated) entry mechanism is
activated by the depletion of SR Ca2+ with ryanodine, as is the case with
inhibitors of SR Ca2+-ATPase.
PMID- 11012903
TI - Changes in conjugated linoleic acid and its metabolites in patients with chronic
renal failure.
AB - BACKGROUND: Conjugated linoleic acid (CLA) is a mixture of isomers of linoleic
acid with conjugated double bonds that constitutes the most abundant fatty acid
with conjugated dienes (CDs) in humans. CLA, erroneously considered in the past
as a product of lipoperoxidation, has a dietary origin and has shown to possess
anticarcinogenic and anti-atherogenic activity, mainly in animal studies. CLA can
be metabolized to conjugated linolenic acid (CD18:3) and to conjugated
eicosatrienoic acid (CD20:3) and these metabolites may be implicated in CLA
activity. Because of the presence of dyslipidemia and the high incidence of
cardiovascular and neoplastic diseases in uremic patients, we evaluated CLA and
its metabolites in these patients in order to evaluate their metabolism and site
distribution. METHODS: We measured CLA, CD18:3, CD20:3, CD fatty acid
hydroperoxides (lipoperoxidation products), and linoleic acid in the plasma,
adipose tissue, and red blood cell (RBC) membranes by using high-pressure liquid
chromatography in the following groups: (1) 23 chronic renal failure (CRF)
patients with creatine clearance (CCr)> 10 mL/min (26.2 +/- 16.7); (2) 21 end
stage CRF patients in conservative treatment with CCr <10 mL/min (6.8 +/- 1.8);
(3) 30 hemodialysis (HD) patients; and (4) 30 healthy controls. RESULTS: The
incorporation of CLA, CD18:3, and CD20:3 in RBC membranes was significantly
reduced in group 1 and was even more reduced in groups 2 and 3. CLA significantly
increased both in the plasma and adipose tissue of end-stage CRF patients only.
CD18:3 and CD20:3 did not change in the plasma and adipose tissue of any group.
No significant changes in linoleic acid and CD fatty acid hydroperoxides were
found. CONCLUSIONS: The alterations of CD in CRF patients are not due to
lipoperoxidation. The increased levels of CLA in plasma and adipose tissue of end
stage CRF patients may be due either to a reduced metabolization of CLA to CD18:3
and CD20:3, or to an altered site distribution with reduced incorporation in
cellular membranes and accumulation in the plasma and adipose tissue. The
clinical significance of these changes remains to be investigated.
PMID- 11012904
TI - Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects:
The Insulin Resistance Atherosclerosis Study.
AB - BACKGROUND: Microalbuminuria is a risk factor for cardiovascular disease, but the
underlying pathomechanisms are still poorly understood. A relationship between C
reactive protein (CRP), a sensitive marker of inflammation, and atherosclerotic
disease has been reported recently. METHODS: We hypothesized that
microalbuminuria might be associated with chronic inflammation and investigated
the relationship of urinary albumin excretion, as assessed from the albumin-to
creatinine ratio (ACR), in an untimed morning urine specimen, and two
inflammatory markers (CRP and fibrinogen) in the large, triethnic population of
the Insulin Resistance Atherosclerosis Study (IRAS). After exclusion of subjects
with macroalbuminuria, 1481 subjects were studied. RESULTS: Both inflammatory
markers were related to urinary ACR (r = 0.17 for CRP and r = 0.14 for
fibrinogen, both P = 0.0001), an association that remained significant after
adjustment for demographic variables, diabetic status, smoking, and use of
angiotensin-converting enzyme inhibitors (P < 0.01). Mean levels of CRP and
fibrinogen were elevated in microalbuminuric (N = 262) versus normoalbuminuric (N
= 1219) subjects (5.37 +/- 0.47 vs. 3.80 +/- 0.15 mg/L and 295.7 +/- 4. 0 vs.
278.2 +/- 1.6 mg/dL, both P < 0.0001). The associations were consistent among
nondiabetic and type 2 diabetic subjects and among the three ethnic groups of the
IRAS (non-Hispanic whites, blacks, Hispanics). In a logistic regression model,
fibrinogen was independently associated with microalbuminuria (P = 0.047), along
with hypertension, female gender, waist circumference, and fasting blood glucose,
while CRP was not independently related to microalbuminuria in this model (P =
0.26). CONCLUSION: We have shown an association of CRP and fibrinogen with
urinary albumin excretion in the microalbuminuric range in type 2 diabetic and
nondiabetic individuals. Chronic inflammation therefore emerges as a potential
mediator between microalbuminuria and macrovascular disease.
PMID- 11012905
TI - Renal function and blood pressure five years after puumala virus-induced
nephropathy.
AB - BACKGROUND: Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with
renal syndrome caused by Puumala hantavirus. Its long-term prognosis is
considered favorable. Some reports suggest, however, that a previous hantavirus
infection increases the risk of hypertension. METHODS: We studied 46 previously
healthy subjects (26 males and 20 females, mean age of 44 years) who had
serologically confirmed NE three to seven years previously, and 38 healthy,
seronegative controls (22 males and 16 females, mean age of 44 years). Ambulatory
blood pressure (ABP) was monitored. Glomerular filtration rate (GFR) and
effective renal plasma flow (ERPF) were determined by 51CrEDTA and 131I-hippurate
clearances, respectively. The filtration fraction (FF) was calculated.
Quantitative 24-hour urinary protein excretion (UprotE) and timed overnight
urinary excretion of alpha1-microglobulin were measured. RESULTS: The NE patients
had a higher mean ambulatory systolic BP than the controls (123 +/- 13 vs. 117 +/
9 mm Hg, P = 0. 008). GFR and FF were increased in patients compared with
controls (GFR, 120 +/- 20 vs. 109 +/- 14 mL/min/1.73 m2, P = 0.006; FF, 19 +/- 3
vs. 18 +/- 3%, P = 0.030), but ERPF did not differ between the groups. The
patients also had higher UPE than the controls (median 0. 18 g/day, range 0.12 to
0.38 vs. median 0.14 g/day, range 0.09 to 0. 24, P < 0.001, respectively). The
overnight urinary excretion rate of alpha1-microglobulin exceeded 7 microg/min in
nine patients. CONCLUSION: Three to seven years after NE, the patients had higher
GFR and FF, more proteinuria, and higher ambulatory systolic BP compared with the
healthy controls. NE may thus cause mild renal lesions and alterations in BP in
some patients.
PMID- 11012906
TI - Causes of albuminuria in patients with type 2 diabetes without diabetic
retinopathy.
AB - BACKGROUND: The causes of albuminuria in patients with type 2 diabetes are
heterogeneous and are scantily investigated, particularly if the patient has a
lack of diabetic retinopathy. Therefore, we evaluated the structural background
of albuminuria in a large consecutive group of Caucasian patients with type 2
diabetes without retinopathy. METHODS: Three hundred forty-seven consecutive
patients with type 2 diabetes with persistent albuminuria (>300 mg/24 h) were
recorded. Fundus photo (80%) and ophthalmoscopy were performed. Ninety-three
(27%) had no retinopathy, and a kidney biopsy was performed in 52 (56%) of these
patients. An insufficient tissue sample was obtained in one patient. The biopsies
were evaluated by three masked nephropathologists. RESULTS: The biopsies revealed
diabetic glomerulopathy in 69% of the patients (28 males and 7 females), while
the remaining 31% (95% CI, 18 to 44) had either nondiabetic glomerulopathies such
as glomerulonephritis (N = 7, 6 males and 1 female, 13%) or normal glomerular
structure (N = 9, 7 males and 2 females, 18%). No significant differences in sex,
age (56 +/- 8 vs. 53 +/- 10 years, mean SD), body mass index (30 +/- 4 vs. 31 +/-
8 kg/m2), known duration of diabetes (6 +/- 6 vs. 4 +/- 3 years), GFR (95 +/- 29
vs. 89 +/- 31 mL/min/1.73 m2), albuminuria (1304 +/- 169 to 4731 vs. 1050 +/- 181
to 5176 mg/24 hours), blood pressure (150/87 +/- 16/9 vs. 145/89 +/- 16/9 mm Hg),
prevalence of hypertension (89 vs. 100%), hemoglobin A1c (8.2 +/- 1.6% vs. 9.0 +/
2.5%), and serum total cholesterol (7.1 +/- 2.4 vs. 6.3 +/- 1.6 mmol/L) were
found between patients with and without diabetic glomerulopathy. CONCLUSIONS:
Albuminuric patients with type 2 diabetes without diabetic retinopathy have a
prevalence of biopsies with normal glomerular structure or nondiabetic kidney
diseases of approximately 30%. A separation between diabetic and nondiabetic
glomerular lesions was not possible based on demographic, clinical, or laboratory
data. Consequently, such patients may require further evaluation, including a
kidney biopsy.
PMID- 11012907
TI - A modern approach to selectivity of proteinuria and tubulointerstitial damage in
nephrotic syndrome.
AB - BACKGROUND: The selectivity of proteinuria, introduced in clinical nephrology in
1960 and useful in predicting steroid responsiveness in nephrotic syndrome, found
little place in clinical practice in subsequent decades, since its assessment did
not appear to help predict histologic diagnosis or determine prognosis. The
amount of proteinuria and the degree of tubulointerstitial damage appeared to be
better predictors of functional outcome. A correlation between them has been
found, referred to some toxicity of proteinuria on tubular cells, but so far no
single feature or component of proteinuria has been identified as being
responsible for this toxicity. METHODS: We evaluated 89 patients with nephrotic
syndrome [9 with minimal change disease (MCD), 29 with primary focal segmental
glomerulosclerosis (FSGS), and 51 with idiopathic membranous glomerulonephritis
(MGN)] to determine if the selectivity of proteinuria was associated with
tubulointerstitial damage. A semiquantitative grading of histologic lesions and
qualitative evaluation of the "tubular" component of proteinuria expressed as a
pattern of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
and as fractional excretion of the low molecular weight (LMW) protein alpha1
microglobulin (FE alpha1m) were used. A second aim of the study was to assess the
predictive value on functional outcome [remission or progression to chronic renal
failure (CRF)] and response to therapy of the selectivity of proteinuria,
considered alone and in combination with FE alpha1m. RESULTS: Proteinuria was
classified as highly selective [selectivity index (SI) < or = 0.10, N = 15],
moderately selective (SI > or = 0.11 < or = 0.20, N = 34), or nonselective (SI >
or = 0.21, N = 40). A significant relationship was found between the SI and the
histologic degree of tubulointerstitial damage (score 0 to 1 vs. score > or =2, P
= 0.000), severity of the tubular component of proteinuria (mixed SDS-PAGE
pattern with LMW proteins not lower than 23 kD vs. mixed pattern with LMW
proteins up to 20 to 10 kD, P = 0.000), and FE alpha1m (values below vs. above a
defined cut-off, P = 0.000). The functional outcome was evaluated in 60 patients
with baseline normal renal function (serum creatinine 0.97 +/- 0.19 mg/dL). The
patients with high, moderate, or nonselective proteinuria had 100, 50, and 29% of
complete or partial remission (P = 0.0001) and 0, 25, and 35% of progression to
CRF, respectively (P = 0.050). In 45 patients with moderately selective (N = 28)
and nonselective (N = 17) proteinuria, according to some arbitrary cutoffs for FE
alpha1m (MGN, < or = vs. > 0. 240% of creatinine clearance; FSGS and MCD, < or =
vs. > 0.350%), the remission rate was 62 versus 6% in patients with FE alpha1m
below or above the cutoffs (P = 0.0001), and progression to CRF was 7 and 69%,
respectively (P = 0.0001). The response to therapy (complete or partial remission
at the last observation), evaluated retrospectively in 40 patients, was 100, 67,
and 33% in high, moderate, and nonselective proteinuria (P = 0.0002); in 30
patients with moderate and nonselective proteinuria, according to an FE alpha1m
value that was < or = or > the cutoffs, the response rate was 75 versus 10% (P =
0.001). CONCLUSIONS: There is a significant relationship between selectivity of
proteinuria and tubulointerstitial damage. Moreover, the selectivity of
proteinuria has a predictive value on functional outcome. When proteinuria is
highly selective, the tubulointerstitial damage is rather infrequent, and 100% of
patients develop clinical remission. When proteinuria is moderately selective or
nonselective, increasing numbers of patients develop tubulointerstitial damage;
in these patients, the functional outcome and response to therapy is partly
dependent on tubulointerstitial involvement, and the best predictor of functional
outcome is the combination of SI and FE alpha1m.
PMID- 11012908
TI - Serum C-peptide concentrations poorly phenotype type 2 diabetic end-stage renal
disease patients.
AB - BACKGROUND: A homogeneous patient population is necessary to identify genetic
factors that regulate complex disease pathogenesis. In this study, we evaluated
clinical and biochemical phenotyping criteria for type 2 diabetes in end-stage
renal disease (ESRD) probands of families in which nephropathy is clustered. C
peptide concentrations accurately discriminate type 1 from type 2 diabetic
patients with normal renal function, but have not been extensively evaluated in
ESRD patients. We hypothesized that C-peptide concentrations may not accurately
reflect insulin synthesis in ESRD subjects, since the kidney is the major site of
C-peptide catabolism and would poorly correlate with accepted clinical criteria
used to classify diabetics as types 1 and 2. METHODS: Consenting diabetic ESRD
patients (N = 341) from northeastern Ohio were enrolled. Clinical history was
obtained by questionnaire, and predialysis blood samples were collected for C
peptide levels from subjects with at least one living diabetic sibling (N = 127,
48% males, 59% African Americans). RESULTS: Using clinical criteria, 79% of the
study population were categorized as type 1 (10%) or type 2 diabetics (69%),
while 21% of diabetic ESRD patients could not be classified. In contrast, 98% of
the patients were classified as type 2 diabetics when stratified by C-peptide
concentrations using criteria derived from the Diabetes Control and Complications
Trial Research Group (DCCT) and UREMIDIAB studies. Categorization was concordant
in only 70% of ESRD probands when C-peptide concentration and clinical
classification algorithms were compared. Using clinical phenotyping criteria as
the standard for comparison, C-peptide concentrations classified diabetic ESRD
patients with 100% sensitivity, but only 5% specificity. The mean C-peptide
concentrations were similar in diabetic ESRD patients (3.2 +/- 1.9 nmol/L) and
nondiabetic ESRD subjects (3.5 +/- 1.7 nmol/L, N = 30, P = NS), but were 2.5-fold
higher compared with diabetic siblings (1.3 +/- 0.7 nmol/L, N = 30, P < 0.05)
with normal renal function and were indistinguishable between type 1 and type 2
diabetics. Although 10% of the diabetic ESRD study population was classified as
type 1 diabetics using clinical criteria, only 1.5% of these patients had C
peptide levels less than 0.20 nmol/L, the standard cut-off used to discriminate
type 1 from type 2 diabetes in patients with normal renal function. However, the
criteria of C-peptide concentrations> 0.50 nmol/L and diabetes onset in patients
who are more than 38 years old identify type 2 diabetes with a 97% positive
predictive value in our ESRD population. CONCLUSIONS: Accepted clinical criteria,
used to discriminate type 1 and type 2 diabetes, failed to classify a significant
proportion of diabetic ESRD patients. In contrast to previous reports, C-peptide
levels were elevated in the majority of type 1 ESRD diabetic patients and did not
improve the power of clinical parameters to separate them from type 2 diabetic or
nondiabetic ESRD subjects. Accurate classification of diabetic ESRD patients for
genetic epidemiological studies requires both clinical and biochemical criteria,
which may differ from norms used in diabetic populations with normal renal
function.
PMID- 11012909
TI - Effects of bicarbonate- and lactate-buffered replacement fluids on cardiovascular
outcome in CVVH patients.
AB - BACKGROUND: Bicarbonate-buffered replacement fluid (RF-bic) in continuous
venovenous hemofiltration (CVVH) may be superior to lactate-buffered replacement
fluid (RF-lac) in acute renal failure. In an open, randomized, multicenter study,
we investigated the effects of RF-bic and RF-lac on cardiovascular outcome in
patients requiring CVVH following acute renal failure. METHODS: One hundred
seventeen patients between the age of 18 and 80 years were randomized to CVVH
either with RF-bic (N = 61) or RF-lac (N = 56). Patients were treated with CVVH
for five days or until either renal function was restored or the patient was
removed from the study. Data were analyzed on day 5 or according to the "last
observation carried forward" (LOCF) option. Adverse events were classified
according to the WHO-Adverse Reaction Terminology system. RESULTS: Blood lactate
levels were significantly lower and blood bicarbonate levels were significantly
higher in patients treated with RF-bic than in those treated with RF-lac
(lactate, 17.4 +/- 8.5 vs. 28.7 +/- 10.4 mg/dL, P < 0.05; bicarbonate, 23.7 +/-
0.4 vs. 21.8 +/- 0.5 mmol/L, P < 0. 01). The number of hypotensive crises was
lower in RF-bic-treated patients than in RF-lac-treated patients (RF-bic 14 out
of 61 patients, RF-lac in 29 out of 56 patients; 0.26 +/- 0.09 vs. 0.60 +/- 0.31
episodes per 24 h, P < 0.05). Nine out of 61 patients (15%) treated with RF-bic
and 21 out of 56 patients (38%) treated with RF-lac developed cardiovascular
events during CVVH therapy (P < 0. 01). A multiple regression analysis showed
that the occurrence of cardiovascular events was dependent on replacement fluid
and previous cardiovascular disease and not on age or blood pressure. Patients
with cardiac failure died less frequently in the group treated with RF-bic (7 out
of 24, 29%) than in the group treated with RF-lac (12 out of 21, 57%, P = 0.058).
In patients with septic shock, lethality was comparable in both groups (RF-bic,
10 out of 27, 37%; RF-lac, 7 out of 20, 35%, P = NS). CONCLUSIONS: The results
show that the administration of RF-bic solution was superior in normalizing
acidosis of patients without the risk of alkalosis. The data also suggest that
the use of RF-bic during CVVH reduces cardiovascular events in critically ill
patients with acute renal failure, particularly those with previous
cardiovascular disease or heart failure.
PMID- 11012910
TI - Mortality caused by sepsis in patients with end-stage renal disease compared with
the general population.
AB - BACKGROUND: In the United States, infection is second to cardiovascular disease
as the leading cause of death in patients with end-stage renal disease (ESRD),
and septicemia accounts for more than 75% of this category. This increased
susceptibility to infections is partly due to uremia, old age, and comorbid
conditions. Although it is intuitive to believe that mortality caused by sepsis
may be higher in patients with ESRD compared with the general population (GP), no
such data are currently available. METHODS: We compared annual mortality rates
caused by sepsis in patients with ESRD (U.S. Health Care Financing Administration
2746 death notification form) with those in the GP (death certificate). Data were
abstracted from the U.S. Renal Data System (1994 through 1996 Special Data
request) and the National Center for Health Statistics. Data were stratified by
age, gender, race, and diabetes mellitus (DM). Sensitivity analyses were
performed to account for potential limitations of the data sources. RESULTS:
Overall, the annual percentage mortality secondary to sepsis was approximately
100- to 300-fold higher in dialysis patients and 20-fold higher in renal
transplant recipients (RTRs) compared with the GP. Mortality caused by sepsis was
higher among diabetic patients across all populations. After stratification for
age, differences between groups decreased but retained their magnitude. These
findings remained robust despite a wide range of sensitivity analyses. Indeed,
mortality secondary to sepsis remained approximately 50-fold higher in dialysis
patients compared with the GP, using multiple cause-of-death analyses; was
approximately 50-fold higher in diabetic patients with ESRD compared with
diabetic patients in the GP, when accounting for underreporting of DM on death
certificates in the GP; and was approximately 30-fold higher in RTRs compared
with the GP, when accounting for the incomplete ascertainment of cause of death
among RTRs. Furthermore, despite assignment of primary cause-of-death to major
organ infections in the GP, annual mortality secondary to sepsis remained 30- to
45-fold higher in the dialysis population. CONCLUSIONS: Patients with ESRD
treated by dialysis have higher annual mortality rates caused by sepsis compared
with the GP, even after stratification for age, race, and DM. Consequently, this
patient population should be considered at high-risk for the development of
lethal sepsis.
PMID- 11012912
TI - Unrestricted pore area (A0/Deltax) is a better indicator of peritoneal membrane
function than PET.
AB - BACKGROUND: How to measure the peritoneal exchange in uremic patients treated
with peritoneal dialysis (PD) is still a matter of controversy. Most clinics use
the peritoneal equilibration test (PET), but from a theoretical point of view, it
would be more appropriate to determine the "area" parameter, A0/Deltax. The
latter reflects the total unrestricted pore area per centimeter diffusion
distance and can be obtained by three-pore analysis using, for example, the PD
capacity test (PDC). To evaluate the different estimates of peritoneal function,
PET data and the A0/Deltax parameters were compared with the independently
determined uptake of a small diffusible tracer, iohexol (molecular weight of 821
D), from the abdominal cavity to blood. METHODS: Fourteen patients on routine PD
underwent determinations of PET and A0/Deltax using PDC. Within a month, the two
hour uptake of iohexol (6 mg/mL) was also determined from the plasma iohexol
concentration following abdominal filling. RESULTS: A strong correlation was
found between the rate of iohexol plasma concentration increase (k30-120) and
A0/Deltax (A0/Deltax = 76,300. k30-120 - 1.56; r2 = 0.799; N = 14) for the 2 L
dwell, while the PET data were far less related to iohexol uptake (D/DPurea, r2 =
0.409; D/Pcreatinine, r2 = 0.436; and D/D0glucose, r2 = 0.015, respectively).
CONCLUSION: The "area" parameter, A0/Deltax, is superior to the more widely used
routine PET as an indicator of peritoneal membrane function. In addition, the
concept of A0/Deltax has the virtue of supplying quantitative information about
the peritoneal pathophysiology and physiology.
PMID- 11012911
TI - Effects of lactate-buffered and lactate-free dialysate in CAVHD patients with and
without liver dysfunction.
AB - BACKGROUND: Continuous modalities of renal replacement deplete patients of
bicarbonate, which is traditionally replaced indirectly by lactate in dialysate
or replacement fluids. We have compared a new lactate-free dialysate (unbuffered
dialysate with separate bicarbonate replacement of dialytic bicarbonate loss)
with standard lactate-buffered dialysate in terms of acid-base control, lactate
accumulation, and hemodynamic stability in patients undergoing continuous renal
replacement therapy in an intensive care unit. METHODS: A nonrandomized crossover
cohort study involving 54 patients with multi-organ failure (of whom 19 had
significant hepatic dysfunction) was performed. All patients completed 24-hour
continuous hemodiafiltration against both lactate-buffered and lactate-free
dialysate. Arterial pH, blood gases, bicarbonate, and lactate, venous sodium,
blood pressure, and inotrope requirements were measured before and at six hourly
intervals during the first 24 hours of dialysis against each dialysate. RESULTS:
Lactate-free dialysate provided more rapid control of acidosis than lactate
buffered with less total administration of buffer than that given during the
lactate-buffered period (total mmol bicarbonate vs. total mmol lactate +
bicarbonate). Lactate accumulation was slight in both periods, but was higher
during lactate-buffered continuous venovenous hemodiafiltration (CVVHD). The mean
arterial pressure rose during lactate-free dialysis with decreased inotrope doses
and fell during lactate-buffered dialysis with increased inotrope requirement.
Results in patients with liver dysfunction were not significantly different from
those without it. CONCLUSIONS: Over the time scale of 24 hours, lactate derived
from continuous dialysis circuits is efficiently cleared from the blood of most
patients with multi-organ failure, but with less effect on systemic acidosis than
is produced by equivalent amounts of bicarbonate.
PMID- 11012913
TI - Nitric oxide inhibits the formation of advanced glycation end products.
AB - BACKGROUND: Advanced glycation end products (AGEs) are elevated in renal failure
and have been implicated in the pathogenesis of several uremic complications.
Their formation is closely associated with oxidative stress. The recent
observation that nitric oxide (NO) has an antioxidant effect led us to examine
the possible role of NO in the generation of AGEs. METHODS: We examined the
effect of NO donors, 2, 2'-(hydroxynitrosohydrazono)bis-ethanamine (NOC18) and S
nitroso-N-acetyl-DL-penicillamine (SNAP), on the in vitro formation of
pentosidine, which was used as a surrogate marker for AGEs. Bovine serum albumin
was incubated under air at 37 degrees C in a medium containing either several AGE
precursors or uremic plasma. To elucidate further the mechanism of the NO effect
on AGE formation, we examined the generation of free radicals and carbonyls in
pentose-driven pentosidine formation. RESULTS: NO donors significantly inhibit
the formation of pentosidine in a dose-dependent manner. The effect is abolished
by the addition of a NO scavenging agent, 2-(4-carboxyphenyl)-4,4,5, 5
tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO). The inhibitory effect
results from NO but not from the NO donor molecule. It is best explained by the
ability of NO to scavenge carbon-centered radicals, hydroxyl radical, and
carbonyl compounds. CONCLUSIONS: NO inhibits pentosidine formation by scavenging
free radicals and by inhibiting carbonyl compound formation. NO might be
implicated in the atherogenic and inflammatory effects of AGEs: Reduced NO
production and increased oxidative stress associated with atherosclerotic lesions
may accelerate AGE formation and, thus, exacerbate endothelial dysfunction and
accelerate the development of atherosclerosis in uremia.
PMID- 11012914
TI - Cyclosporine bone remodeling effect prevents steroid osteopenia after kidney
transplantation.
AB - BACKGROUND: It is well established that prednisone above 7.5 mg/day may induce
osteopenia in association with decreased bone formation. In contrast, the effect
of cyclosporine on bone remodeling and bone mineral density (BMD) is
controversial. Multiple confounding factors explain this controversy, especially
after renal transplantation. METHODS: Fifty-two renal transplanted patients never
exposed to aluminum while on dialysis were selected because they had no rejection
and no hypercalcemia for 24 months while being treated with low dose
prednisone/cyclosporine A (daily dose at 10 mg and 4.8 mg/kg, respectively,
beyond 3 months). Bone remodeling markers (BRMs; plasma osteocalcin, bone and
total alkaline phosphatases for formation, and urinary pyridinolines for
resorption) were sequentially measured together with plasma creatinine, intact
parathyroid hormone (PTH) and 25 OH vitamin D and cyclosporine from day 0 to 24
months. BMD was measured at 3, 6, 12, and 24 months by quantitative computerized
tomography (QCT) at the lumbar spine and by double-energy x-ray absorptiometry
(DEXA) at this site, as well as at the femoral neck, radius shaft, and
ultradistal (UD) radius. RESULTS: Plasma concentrations of creatinine, PTH, and
25 OH vitamin D initially decreased and stabilized beyond three months at 137
micromol/L, 1.5 the upper limit of normal (ULN) and 11 ng/mL, respectively. All
BRM increased significantly above the ULN at six months and then decreased. The
BMD Z score at three months was low at all sites measured by DEXA and QCT. Follow
up measurements showed stability of absolute value and of Z score at all sites
measured by DEXA. A comparison of the lumbar QCT Z score, which was available in
42 patients at 3 and 24 months, showed an increase in 28 and a decrease in 14, so
that the increase for the whole group was significant (P < 0.04). Compared with
patients with a decreased Z score, those with an increased Z score had
significantly higher cyclosporine and lower prednisone dosages and a greater BRM
increase at six months, whereas age, sex ratio, and plasma creatinine, PTH and 25
OH vitamin D were comparable and stable from months 3 through 24. The mean trough
level of cyclosporine for the first six months was positively correlated to
osteocalcin and total alkaline phosphatase increase at six months, and both bone
formation and resorption marker increases were significantly correlated to the
lumbar QCT Z score increase at 24 months. CONCLUSIONS: Combined low-dose
prednisone and cyclosporine immunosuppression are associated with a stabilization
of BMD measured at all sites with DEXA 3 to 24 months after renal transplantation
and with a prevention of age-related loss of vertebral trabecular bone, as shown
by the significant increase in lumbar spine QCT Z score. It is suggested that
cyclosporine, together with the decrease of prednisone dosage but independent of
renal function, PTH, and vitamin D status, contributes to a transient stimulation
of bone remodeling at six months, which counterbalances the deleterious effect of
prednisone on bone formation and BMD.
PMID- 11012915
TI - Progressive adriamycin nephropathy in mice: sequence of histologic and
immunohistochemical events.
AB - BACKGROUND: As an experimental analogue of human focal glomerular sclerosis
(FGS), adriamycin (ADR)-induced nephropathy is well-characterized in rats.
Previously, this model has not been fully established in mice. The extension of
this model to the mouse would be useful in the application of genetic and
monoclonal antibody technology to characterize mechanisms of progressive renal
disease. Herein, we describe a stable and reproducible murine model of chronic
proteinuria induced by ADR. METHODS: Male BALB/c mice were intravenously injected
with a single dose of ADR (10 to 11 mg/kg). Seven mice were sacrificed at weeks
1, 2, 4, and 6. Renal function, quantitative morphometric analysis, and electron
microscopic studies were performed. Peripheral CD4+ and CD8+ T cells were
evaluated using flow cytometric analysis of splenocytes. The leukocytic
inflammatory pattern was analyzed by immunohistochemical examination. RESULTS:
Overt proteinuria was observed from day 5 and remained significantly elevated
throughout the study period. A focal increase in reabsorption droplets in tubular
cells appeared at weeks 1 and 2, and numerous intraluminal casts were present
after two weeks. Glomerular vacuolation and mild FGS appeared at week 4. At week
6, extensive focal and even global glomerular sclerosis, associated with moderate
interstitial expansion and severe inflammation, were observed. A prominent
macrophage infiltration appeared within both interstitium and glomeruli at week
2, followed by accumulation of both CD4+ and CD8+ T cells in interstitium but not
glomeruli. There were almost no B lymphocytes seen at any time. CONCLUSION: This
model should be useful in unraveling the pathogenesis of glomerular and
interstitial inflammation and fibrosis in chronic proteinuric renal disease.
PMID- 11012916
TI - Computational analysis of blood volume curves and risk of intradialytic morbid
events in hemodialysis.
AB - BACKGROUND: Blood volume (BV) curves have been used to prevent intradialytic
morbid events (IMEs) caused by hypotensive episodes in hemodialysis treatment.
However, no standardized parameter is available to describe BV dynamics and to
enable online interference with ultrafiltration rates in unselected patients.
Moreover, only time-dependent BV reduction and absolute hematocrit threshold, but
not BV variability, have been suggested as markers of pending hypotension. The
present study therefore deals with a computer-aided analysis of indices
characterizing both BV reduction per time and BV variability in treatments of
nonselected maintenance hemodialysis patients. METHODS: The methodology uses
indices obtained by mathematical analysis of BV curves and was designed to
potentially enable automatic interference with ultrafiltration. RESULTS: In 46
out of 380 treatments (12.1%), IMEs occurred. In these treatments, the indices
for long- and short-term variability and slope of the curves were significantly
lower than in treatments without IMEs. Moreover, the last 10 minutes before an
IME were characterized by additionally decreased variability and slope. In a risk
analysis of long-term variability and IMEs, we established an index below 16 to
be associated with the highest risk of IMEs. CONCLUSIONS: Using these kind of
index thresholds and online analysis of BV curves, automatic management of
ultrafiltration by BV dynamics could be a promising concept to avoid
intradialytic morbidity.
PMID- 11012917
TI - Color doppler ultrasonography imaging to guide transluminal angioplasty of venous
stenosis.
AB - BACKGROUND: The objective of access surveillance is the early recognition of
dysfunction in order to be able to correct the stenosis by angioplasty or surgery
before access thrombosis occurs. The advent of color Doppler imaging has enabled
studies of color Doppler ultrasonography (CDU) for the guidance of percutaneous
transluminal angioplasty (PTA). The aim of the present study was to investigate
whether color Doppler imaging alone can be safely and effectively used to
diagnose vascular graft access stenoses and guide subsequent PTA. METHODS: Using
the ultrasound velocity dilution method, we measured access blood flow (Qa)
during the first hour of hemodialysis every month in patients with grafts as
vascular access. When the decrease in Qa from the baseline value was 40% or more,
CDU was performed and immediately followed by PTA in the presence of a stenosis
of more than 50%. The Qa was then measured during the first dialysis after PTA
and one month later. Repeated-measure analysis of variance was applied to
evaluate the early and late (after one month) effect of PTA. RESULTS: Twelve PTAs
were performed under CDU guidance in nine patients and led to the elimination of
the stenosis or its reduction (two cases). The mean Qa was 809 +/- 263 mL/min at
baseline, 468 +/- 153 before PTA, and 820 +/- 281 after PTA. The difference
between the pre-PTA and post-PTA values was highly significant (P < 0.001), and
the mean value after PTA was not different from baseline (P = 0.672). There were
no relevant complications directly related to the procedure. CONCLUSIONS: The CDU
procedure is effective for the diagnosis of vascular access stenosis and as a
guide during the PTA procedure. It could improve stenosis screening by avoiding
the risks of exposure to ionizing radiation and of adverse reactions to contrast
media.
PMID- 11012918
TI - Nitric oxide, advanced glycation end products, and uremia.
PMID- 11012919
TI - Light from DARCness.
PMID- 11012921
TI - Reply from the authors
PMID- 11012920
TI - Renoprotection and blood pressure.
PMID- 11012923
TI - In this issue
PMID- 11012922
TI - Expanding the kidney donor pool: ethical and medical considerations.
PMID- 11012924
TI - The Cambridge Conference: background.
PMID- 11012925
TI - Combining marks, scores and grades. Reviewing common practices reveals some bad
habits.
PMID- 11012926
TI - Academic medicine In progress: reports of new approaches in medical education
PMID- 11012927
TI - Marks, scores and grades: scaling and aggregating student assessment outcomes.
AB - The term marks conflates the concepts of scores (raw test performance) and grades
(level of performance). Neither scores nor grades represent interval scales, and
therefore properly speaking arithmetic means should not be calculated during
aggregation. The distributions of scores from a variety of kinds of assessment
are considered, and ways of converting scores to grades are discussed. Methods of
aggregation are also considered, and several strategies for implementing these
via spreadsheets are made available. It is recommended that: 1 Scores should
always be converted to grades before aggregation. The process of converting
scores to grades requires both subject-specific skills, and familiarity with
educational principles. 2 Whatever grade scale is used, it should be readily
distinguishable from scores. 3 The median should be calculated as the measure of
overall performance, not the arithmetic mean. 4 The interquartile range should be
calculated as the measure of dispersion. 5 Students should be informed of both
their score and grade for each assessment. 6 Where possible, assessment should
report performance by individual assessment, not by a single aggregated mark. 7
When aggregation takes place, it should be possible to aggregate student
performance by type of assessment as well as by academic subject. 8 Students who
perform inconsistently should receive particular scrutiny during assessment.
PMID- 11012928
TI - Development of a three-centre simultaneous objective structured clinical
examination.
AB - OBJECTIVE: To describe the development, organization, implementation and
evaluation of a yearly multicentre, identical and simultaneous objective
structured clinical examination (OSCE). SUBJECTS: All fifth-year medical students
in a 6-year undergraduate medical programme. SETTING: The Christchurch, Dunedin
and Wellington Schools of Medicine of the University of Otago, New Zealand.
METHOD: One practice and two full 18-station OSCEs have been completed over 2
years, for up to 72 students per centre, in three centres. The process of
development and logistics is described. Data are presented on validity,
reliability and fairness. RESULTS: Face and content validity were established.
Internal consistency was 0.83-0. 86 and interexaminer reliability, as assessed by
the coefficient of correlation, averaged 0.78. Students rated the OSCE highly on
relevance. Of the total variance in total OSCE marks, the schools contributed
6.9%, and the students 93.1%, in the first year. In the second year the schools
contributed 6.2% and the students 93.8%. CONCLUSION: Implementation of a
psychometrically sound, multicentre, simultaneous and identical OSCE is possible
with a low level of interschool variation.
PMID- 11012929
TI - Does studying for an objective structured clinical examination make a difference?
AB - PURPOSE: This study examines the extent to which second-year medical students
studied for an objective structured clinical examination (OSCE), how they
studied, and the impact of self-reported studying on OSCE performance. METHOD:
One class of 113 medical students completed an end-of-second-year OSCE, held on
two consecutive evenings. The OSCE was comprised of eight stations, each of which
was of 20 minutes' duration. The OSCE was formative: students received
performance feedback but were not graded. Prior to the OSCE, students completed a
brief survey regarding their preparation for the OSCE and their perceptions of
confidence, anxiety and preparedness. Only 78 students returned surveys with
names, comprising the data for these analyses. RESULTS: Mean studying time was
3.3 h, ranging from 0 to 19 h. Studying time was positively associated with age
and negatively associated with basic science examination scores. The most study
time was dedicated to reviewing the physical examination textbook, class notes
and supplemental course readings. The breadth of study strategies increased as
more time was spent in OSCE preparation. OSCE performance was related to study
time and to achievement on pre-clinical basic science examinations. DISCUSSION:
The students whose performance was above average seemed to be the talented
students whose records indicated a history of academic success. The amount of
time they reported for OSCE preparation was comparable to that reported by
students with below average performance. It appears that prior academic
performance rather than preparatory studying time is a better predictor of OSCE
outcomes.
PMID- 11012930
TI - The management of patient encounter time in a high-stakes assessment using
standardized patients.
AB - OBJECTIVES: The purpose of this study was to gather information regarding the
appropriateness of the length of time allotted for candidates to complete the
history taking and physical examination tasks in a high-stakes standardized
patient (SP) assessment. DESIGN: Data were collected on actual time used by 1548
examinees for each of their 10 standardized patient encounters, for which a
maximum of 15 minutes was allotted, but not required. SETTING: The Clinical
Skills Assessment Center of the Educational Commission for Foreign Medical
Graduates (ECFMG), Philadelphia, Pennsylvania, USA. SUBJECTS: Graduates of
foreign medical schools who are seeking ECFMG certification. RESULTS: The average
time spent with the standardized patient was 13.3 minutes, suggesting that the 15
minute time limit was sufficient. A positive correlation was found between data
gathering scores and patient interview times. Candidates did tend to spend more
time with SPs presenting with cases involving complex histories, as well as with
cases of chronic conditions. CONCLUSIONS: Candidate time use varied as a function
of type of clinical encounter, providing additional evidence of the content
validity of the Clinical Skills Assessment.
PMID- 11012931
TI - Introduction to the papers from the ninth cambridge conference on medical
education
PMID- 11012932
TI - Clinical teaching: maintaining an educational role for doctors in the new health
care environment.
AB - CONTEXT AND OBJECTIVES: Good clinical teaching is central to medical education
but there is concern about maintaining this in contemporary, pressured health
care environments. This paper aims to demonstrate that good clinical practice is
at the heart of good clinical teaching. METHODS: Seven roles are used as a
framework for analysing good clinical teaching. The roles are medical expert,
communicator, collaborator, manager, advocate, scholar and professional. RESULTS:
The analysis of clinical teaching and clinical practice demonstrates that they
are closely linked. As experts, clinical teachers are involved in research,
information retrieval and sharing of knowledge or teaching. Good communication
with trainees, patients and colleagues defines teaching excellence. Clinicians
can 'teach' collaboration by acting as role models and by encouraging learners to
understand the responsibilities of other health professionals. As managers,
clinicians can apply their skills to the effective management of learning
resources. Similarly skills as advocates at the individual, community and
population level can be passed on in educational encounters. The clinicians'
responsibilities as scholars are most readily applied to teaching activities.
Clinicians have clear roles in taking scholarly approaches to their practice and
demonstrating them to others. CONCLUSION: Good clinical teaching is concerned
with providing role models for good practice, making good practice visible and
explaining it to trainees. This is the very basis of clinicians as professionals,
the seventh role, and should be the foundation for the further development of
clinicians as excellent clinical teachers.
PMID- 11012933
TI - Effective supervision in clinical practice settings: a literature review.
AB - CONTEXT: Clinical supervision has a vital role in postgraduate and, to some
extent, undergraduate medical education. However it is probably the least
investigated, discussed and developed aspect of clinical education. This large
scale, interdisciplinary review of literature addressing supervision is the first
from a medical education perspective. PURPOSE: To review the literature on
effective supervision in practice settings in order to identify what is known
about effective supervision. CONTENT: The empirical basis of the literature is
discussed and the literature reviewed to identify understandings and definitions
of supervision and its purpose; theoretical models of supervision; availability,
structure and content of supervision; effective supervision; skills and qualities
of effective supervisors; and supervisor training and its effectiveness.
CONCLUSIONS: The evidence only partially answers our original questions and
suggests others. The supervision relationship is probably the single most
important factor for the effectiveness of supervision, more important than the
supervisory methods used. Feedback is essential and must be clear. It is
important that the trainee has some control over and input into the supervisory
process. Finding sufficient time for supervision can be a problem. Trainee
behaviours and attitudes towards supervision require more investigation; some
behaviours are detrimental both to patient care and learning. Current supervisory
practice in medicine has very little empirical or theoretical basis. This review
demonstrates the need for more structured and methodologically sound programmes
of research into supervision in practice settings so that detailed models of
effective supervision can be developed and thereby inform practice.
PMID- 11012934
TI - Strategic planning in medical education: enhancing the learning environment for
students in clinical settings.
AB - BACKGROUND: The 1999 Cambridge Conference was held in Northern Queensland,
Australia, on the theme of clinical teaching and learning. It provided an
opportunity for groups of academic medical educators to consider some of the
challenges posed by recent changes to health care delivery and medical education
across a number of countries. PURPOSE: This paper describes the issues raised by
the practical challenges posed by the current environment and how they might be
addressed in ways that could promote more effective learning in clinical
settings. METHOD: A SWOT analysis is a tool that can help in forward planning by
identifying the strengths, weaknesses, opportunities and threats presented by any
situation. Our SWOT analysis was used to generate a list of items, from which we
chose those most feasible and most likely to promote positive change. RESULTS:
Twenty different issues were identified, with four of them chosen by consensus
for further elaboration. The discussion gave rise to four main recommended
strategies: ensuring that clinical teachers thoroughly understand the purpose and
process of learning in clinical settings; equipping learners with 'survival
skills'; making the best use of learning resources within different clinical
environments and making judicious use of information technology to enhance
learning efficiency. CONCLUSIONS: The four strategies were selected not only
because of their inherent importance, but also because of their feasibility.
Modest changes can motivate students to feel part of a clinical team and a
'community of practice' and enhance their capacity for self-regulated practice.
PMID- 11012936
TI - In-training assessment - its potential in enhancing clinical teaching.
AB - CONTEXT: In-training assessment (ITA) has established its place alongside
formative and summative assessment at both the undergraduate and postgraduate
level. In this paper the authors aimed to identify those characteristics of ITA
that could enhance clinical teaching. METHODS: A literature review and
discussions by an expert working group at the Ninth Cambridge Conference
identified the aspects of ITA that could enhance clinical teaching. RESULTS: The
features of ITA identified included defining the specific benefits to the
learner, teacher and institution, and highlighting the patient as the context for
ITA and clinical teaching. The 'mapping' of a learner's progress towards the
clinical teaching objectives by using multiple assessments over time, by multiple
observers in both a systematic and opportunistic way correlates with the
incremental nature of reaching clinical competence. CONCLUSIONS: The importance
of ITA based on both direct and indirect evidence of what the learner actually
does in the real clinical setting is emphasized. Particular attention is given to
addressing concerns in the more controversial areas of assessor training, ratings
and documentation for ITA. Areas for future research are also identified.
PMID- 11012935
TI - Patient-oriented learning: a review of the role of the patient in the education
of medical students.
AB - AIM: To explore the contribution patients can make to medical education from both
theoretical and empirical perspectives, to describe a framework for reviewing and
monitoring patient involvement in specific educational situations and to generate
suggestions for further research. METHODS: Literature review. RESULTS: Direct
contact with patients can be seen to play a crucial role in the development of
clinical reasoning, communication skills, professional attitudes and empathy. It
also motivates through promoting relevance and providing context. Few studies
have explored this area, including effects on the patients themselves, although
there are examples of good practice in promoting more active participation.
CONCLUSION: The Cambridge framework is a tool for evaluating the involvement of
patients in the educational process, which could be used by curriculum planners
and teachers to review and monitor the extent to which patients are actively
involved. Areas for further research include looking at the 'added value' of
using real, as opposed to simulated, patients; more work on outcomes for patients
(other than satisfaction); the role of real patients in assessment; and the
strengths and weaknesses of different models of patient involvement.
PMID- 11012937
TI - A review of the evaluation of clinical teaching: new perspectives and challenges.
AB - PURPOSE: This article discusses the importance of the process of evaluation of
clinical teaching for the individual teacher and for the programme. Measurement
principles, including validity, reliability, efficiency and feasibility, and
methods to evaluate clinical teaching are reviewed. CONTEXT: Evaluation is
usually carried out from the perspective of the learner. This article broadens
the evaluation to include the perspectives of the teacher, the patient and the
institutional administrators and payers in the health care system and recommends
evaluation strategies. RESULTS: Each perspective provides specific feedback on
factors or attributes of the clinical teacher's performance in the domains of
medical expert, professional, scholar, communicator, collaborator, patient
advocate and manager. Teachers should be evaluated in all domains relevant to
their teaching objectives; these include knowledge, clinical competence, teaching
effectiveness and professional attributes. CONCLUSIONS AND IMPLICATIONS: Using
this model of evaluation, a connection can be made between teaching and learning
about all the expected roles of a physician. This can form the basis for
systematic investigation into the relationship between the quality of teaching
and the desired outcomes, the improvement of student learning and the achievement
of better health care practice. It is suggested that the extent of effort and
resources devoted to evaluation should be commensurate with the value assigned to
the evaluation process and its outcomes.
PMID- 11012938
TI - The accountability of clinical education: its definition and assessment.
AB - BACKGROUND: Medical education is not exempt from increasing societal expectations
of accountability. Competition for financial resources requires medical educators
to demonstrate cost-effective educational practice; health care practitioners,
the products of medical education programmes, must meet increasing standards of
professionalism; the culture of evidence-based medicine demands an evaluation of
the effect educational programmes have on health care and service delivery.
Educators cannot demonstrate that graduates possess the required attributes, or
that their programmes have the desired impact on health care without appropriate
assessment tools and measures of outcome. OBJECTIVE: To determine to what extent
currently available assessment approaches can measure potentially relevant
medical education outcomes addressing practitioner performance, health care
delivery and population health, in order to highlight areas in need of research
and development. METHODS: Illustrative publications about desirable professional
behaviour were synthesized to obtain examples of required competencies and health
outcomes. A MEDLINE search for available assessment tools and measures of health
outcome was performed. RESULTS: There are extensive tools for assessing clinical
skills and knowledge. Some work has been done on the use of professional
judgement for assessing professional behaviours; scholarship; and
multiprofessional team working; but much more is needed. Very little literature
exists on assessing group attributes of professionals, such as clinical
governance, evidence-based practice and workforce allocation, and even less on
examining individual patient or population health indices. CONCLUSIONS: The
challenge facing medical educators is to develop new tools, many of which will
rely on professional judgement, for assessing these broader competencies and
outcomes.
PMID- 11012939
TI - Graeme catto
PMID- 11012940
TI - Residual strain in the gastrointestinal tract: a new concept.
PMID- 11012941
TI - Human postprandial gastric emptying of indigestible solids can occur unrelated to
antral phase III.
AB - According to animal experiments, postprandial gastric emptying of indigestible
solids is mainly related to the antral phase III activity of the migrating motor
complex. Gastric emptying of indigestible solids in humans has not been directly
correlated to pressure recordings. The aim of the present study was to
investigate the postprandial emptying pattern of indigestible solids in humans
and its relation to fed and fasted antral motility. Ten healthy volunteers
participated. After an overnight fast they had a standard breakfast. Two sizes of
radiopaque markers (ROMs) were given with the test meal; ten cubes each of side
measurement 1.5 mm and 3 mm, respectively. Emptying of the ROMs from the stomach
was followed by fluoroscopy with simultaneous antral manometry. In six of the
subjects, fasting antral manometry was performed on one day and on another day,
the emptying of 7 mm cylindrical particles together with 3 mm cubes, in the
absence of a gastric tube was recorded. All ROMs were emptied within 5 h (range
1.5-4.5 h). In all subjects, the smaller particles (1.5 mm) showed a slight,
insignificant tendency to move from the stomach more rapidly than the larger (3
mm) particles. None of the subjects had an antral phase III before all ROMs were
emptied from the stomach. Instead, the typical irregular postprandial pressure
activity was present in all subjects until the emptying was completed.
Furthermore, the highest postprandial motility index during the emptying study
was far below the motility index during phase III, but comparable to the motility
index during late phase II. Emptying of the 7 mm particles occurred significantly
more slowly at 1.5-2.5 h, but otherwise was similar to the emptying of the
smaller particles. There was no difference between emptying of the 3 mm cubes
with or without the presence of the tube. Contrary to common opinion, gastric
emptying of indigestible solids after a meal can occur unrelated to the antral
phase III, at least up to a particle size of 3 mm and perhaps even 7 mm. These
findings are of great importance for the evaluation of gastric emptying of
indigestible solids, including the pharmacodynamics of orally administered drugs.
PMID- 11012942
TI - Acute intraduodenal bile salt depletion leads to strong gallbladder contraction,
altered antroduodenal motility and high plasma motilin levels in humans.
AB - Cholecystokinin is the main hormone involved in postprandial gallbladder
contraction. There is also considerable gallbladder contraction in the fasting
state, associated with phase III of the gastrointestinal migrating motor complex
and release of the hormone motilin. It has been proposed that intraduodenal bile
salts exert a negative-feedback control on postprandial cholecystokinin release
and resulting gallbladder contraction. We wanted to elucidate whether a similar
control mechanism on gallbladder contraction exists in the fasting state. We
therefore performed gallbladder ultrasonography and 24-h antroduodenal motility
registrations and determined plasma cholecystokinin and motilin levels in six
healthy subjects before and after acute (4 g) and chronic (8 days; 8 g day(-1))
oral cholestyramine. Acute cholestyramine strongly decreased gallbladder volumes
and increased motilin without changed cholecystokinin levels. There was a
negative relationship between gallbladder volumes and plasma motilin levels.
Although there was a persistent fasting pattern of antroduodenal motility, its
cycle length was increased (P < 0.03) with markedly longer phase II (P < 0. 005).
Fasting gallbladder volumes 24 h later were still strongly decreased but
gradually increased to pretreatment levels. Before and after 8 days
cholestyramine, interdigestive and postprandial gallbladder emptying, intestinal
migrating motor complex and hormone levels did not differ. We conclude that acute
(but not chronic) intraduodenal bile salt depletion with cholestyramine affects
gallbladder and antroduodenal motility, possibly partly related to motilin
release.
PMID- 11012943
TI - Schistosoma mansoni infection causing diffuse enteric inflammation and damage of
the enteric nervous system in the mouse small intestine.
AB - Schistosomiasis mansoni is a major health problem, mainly occurring in developing
countries. A large proportion of infected individuals suffers from motility
related gastrointestinal problems. In the present study, the diffuse inflammatory
response in the small bowel wall, as compared to the egg-induced granulomatous
inflammation, was investigated. For this purpose, OF1 mice infected with
Schistosoma mansoni 8-16 weeks prior to the experiment, and uninfected control
mice were studied. The ileum showed both a diffuse mucosal inflammation as well
as a granulomatous reaction. The diffuse mucosal inflammation caused an increase
in the thickness of the mucosa, with blunting of the villi. A significant,
transient increase of thickness of the muscularis propria after 12 weeks of
infection was noted. There was an infection-related mast cell infiltrate in the
muscularis propria, consisting of formalin fixation-insensitive connective tissue
mast cells. Ganglionitis of the myenteric plexus was noted. Rarely, ganglia of
the myenteric plexus contained apoptotic cells. A general pharmacological set of
experiments showed a significant increase in intestinal contractility, both to
exogenously administered, as well as to endogenously released neurotransmitters.
Our results demonstrate that S. mansoni infection in the mouse ileum leads to
diffuse specific enteric inflammation that is associated with an enhanced
response to contractile agents.
PMID- 11012944
TI - Endomorphin-1 and -2, endogenous ligands for the mu-opioid receptor, inhibit
striated and smooth muscle contraction in the rat oesophagus.
AB - Recently, morphological evidence for an interaction of autonomic nerve fibres and
extrinsic motor innervation of the rat oesophagus has emerged. The aim of the
present study was to investigate the possible influence of endogenous and
exogenous opioids on rat oesophageal smooth and striated muscle function in
vitro. The entire oesophagus (excluding the lower oesophageal sphincter) with
both Nervi (Nn) vagi, including the Nn recurrentes, was dissected and placed in
an organ bath (100 mL, 37 degrees) with oxygenated Krebs-Ringer buffer.
Contractile activity was measured in a longitudinal direction with a force
transducer. Both Nn vagi were placed on a bipolar platinum electrode 2 cm distant
from the oesophagus. Vagal stimulation (VS), applied for 1 s (40 V, 0.5 ms, 20
Hz) resulted in a biphasic contractile response that was completely blocked by
10(-6) M tetrodotoxin. The first part consisted of a tetanic striated muscle
contraction, as it was abolished by tubocurarine (10(-5) M, n=5) but unaffected
by atropine (10(-6) M, n=3) or hexamethonium (10(-4) M, n=4). In contrast, the
second part was completely inhibited by hexamethonium (10(-4) M) and atropine
(10(-6)M), whereas tubocurarine (10(-5) M) showed no influence, indicating a
stimulation of preganglionic nerve fibres supplying oesophageal smooth muscle
(muscularis mucosae) via relays in myenteric ganglia. In order to characterize
opioid influence on the oesophageal striated and smooth muscle contractility, the
following experiments were carried out. 10(-6) M endomorphin-1 and -2, endogenous
mu-opioid-receptor agonists, reduced the contractile response of the striated (EM
2, -25.1+/-5.3%; n=16), and the smooth muscle (EM-2, -81.9+/-3.3%; n=11). Both
effects were reversible by the opioid receptor antagonist naloxone (10(-6) M) and
therefore, mediated via opioid receptors. Neither SNC-80, an agonist on the delta
opioid-receptor, U-69593, an agonist on the kappa-opioid-receptor, nor
nociceptin, an agonist at the ORL1 (opioid receptor-like) receptor, had a
significant effect on the striated muscle contraction. In contrast to SNC-80, U
69593 and nociceptin inhibited smooth muscle contraction but this relaxation
could not be antagonized by naloxone. None of the opioid receptor antagonists
used had an effect on basal tonus or muscle contraction following VS. Our data
provide evidence for an autonomic modulation of vagal motor innervation of the
striated and smooth oesophageal muscle. Endomorphin-1 and -2, both selective mu
opioid receptor agonists, cause an inhibition of striated and smooth muscle
response which is reversible by naloxone, an opioid receptor antagonist. The
location of the mu-opioid receptor still has to be established.
PMID- 11012945
TI - Increased mast cells in the irritable bowel syndrome.
AB - Mast cells (MC) release potent mediators which alter enteric nerve and smooth
muscle function and may play a role in the pathogenesis of the irritable bowel
syndrome (IBS). The aim of this study was to determine if MC were increased in
the colon of IBS patients compared to controls. Biopsy specimens were obtained
from the caecum, ascending colon, descending colon and rectum of 28 patients: 14
IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was
stained immunohistochemically using a monoclonal mouse antibody for human mast
cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density
of mast cells) was quantified by image analysis. The number of plasma cells,
lymphocytes, eosinophils, neutrophils and macrophages were each graded
semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell
volume density was significantly (P < 0.05) higher in IBS (0.91 +/- 0.18; CI
0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but
not at other sites. Apart from MC, there was no evidence of increased cellular
infiltrate in the IBS group. MC were significantly increased in the caecum of IBS
patients compared to controls. The multiple effects of the intestinal mast cell
alone, or as a participant of a persistent inflammatory response, may be
fundamental to the pathogenesis of IBS.
PMID- 11012946
TI - Involvement of tachykinin NK2 receptors in the modulation of spontaneous motility
in rat proximal colon.
AB - The role of endogenous tachykinins and the mechanisms whereby they act on NK2
receptors, modulating spontaneous motility, were investigated in rat isolated
proximal colon. The mechanical activity was detected as changes in intraluminal
pressure. The NK2 receptor antagonist, MEN 10627, produced a concentration
dependent reduction of the contraction amplitude. [beta-Ala8]-neurokinin A(4-10),
an NK2 receptor agonist, and [Sar9, Met(O2)11]-Substance P ([Sar9, Met(O2)11]
SP), an NK1 receptor agonist, induced a concentration-dependent contractile
response, characterized by an increase in basal tone with superimposed phasic
contractions. MEN 10627 antagonized the response to [beta-Ala8]-neurokinin A(4
10), without affecting that to [Sar9, Met(O2)11]-SP. Tetrodotoxin (TTX),
hexamethonium and Nomega-nitro-L-arginine methyl ester (L-NAME) significantly
reduced the response to MEN 10627. The NK3 receptor agonist, senktide, was able
to activate the nitrergic inhibitory pathway, as it induced a TTX-and L-NAME
sensitive inhibitory effect. [beta-Ala8]-neurokinin A(4-10) was able to
antagonize the inhibitory response to senktide. These findings suggest that
tachykinins acting on NK2 receptors play a role in the modulation of the
spontaneous mechanical activity. The mechanism of this action would be, in part,
acting directly on the smooth muscle cells, and, in part neurogenic, sustained by
nicotinic inputs, and possibly due to inhibition of NO tonic release.
PMID- 11012948
TI - How much do we really know about postobstructive pulmonary oedema?
PMID- 11012947
TI - The spatial behaviour of spike patches in the feline gastroduodenal junction in
vitro.
AB - In the isolated feline gastroduodenal region, the spatial propagation of slow
waves and of individual spikes was reconstructed. Recordings were performed
simultaneously from 240 extracellular electrodes positioned on the serosal
surface across the junction. Results from nine experiments (22 slow waves) showed
that the slow wave never propagated across the gastroduodenal region and that
this block was due to the presence of a zone of quiescence caudal to the pylorus.
In contrast, spikes (n=155) were able to propagate into the quiescent zone,
either from the antrum (15.4%) or from the duodenum (34.0%) and occasionally,
were able to propagate from one organ to the other (10.9%). However, in all
cases, spike conduction was self-limited and activated a local area termed a
'patch'. The length of the patches located in the gastroduodenal region was
significantly longer than in the rest of the duodenum (20.2 mm +/- 9. 7 vs. 9.5
mm +/- 3.2; P < 0.001) indicating a possible enhancement of spike propagation in
this region. In conclusion, in spite of the total conduction block for slow
waves, individual spikes are able to propagate across the gastroduodenal region,
albeit in self-limited areas or 'patches'. These spike patches could form the
building blocks for gastroduodenal coordination.
PMID- 11012949
TI - The perioperative management of children with phaeochromocytoma.
AB - The safe anaesthetic management of a child with a phaeochromocytoma requires an
understanding of the pathophysiology of the disease, together with a thorough
knowledge of its pharmacology, in order to avoid or minimize the potentially
harmful cardiovascular changes that may occur during anaesthesia. Although there
is a considerable amount of information on the management of the adult with
phaeochromocytoma, much less has been written concerning children with the
disease. Children differ significantly from adults in the incidence, location,
presentation and management of this condition and these differences are discussed
here together with some of the more controversial issues of management.
PMID- 11012950
TI - Preoperative psychological preparation for children undergoing ENT operations: a
comparison of two methods.
AB - A psychological preparation programme was developed for outpatient surgery in
children. The purpose of this study was to determine if the programme could
increase retrieval of information and reduce anxiety prior to ENT surgery. After
ethical committee approval, 160 children and their parents were included. Eighty
children (group 1) received conventional verbal information from an ENT nurse,
and another 80 children (group 2) received specific information, including role
play, from a nurse anaesthetist at a preadmission visit. Children's and parents'
experience of premedication, operation theatre (OR), i.v.-needle insertion and
induction of anaesthesia were evaluated from a self-rating questionnaire. The
questionnaire included ratings for anxiety and satisfaction with information and
care. The results indicate a clear improvement of the preoperative acquisition of
knowledge in all age groups. When it comes to alleviation of fear, a positive
effect of the preparation programme was noticed, especially among the younger
children (< 5 years), while preoperative anxiety overall was a significantly
smaller problem among the older children. The effects of the programme were also
related to previous experience of anaesthesia and most beneficial among young
children with such experience. Overall, the most negative procedure reported by
the children was the i.m. injection for premedication (a routine which was
abandoned as a result of the study), followed by the insertion of the i.v.
needle. The parents experienced watching their child fall asleep during induction
of anaesthesia as most negative, followed by the insertion of the i.v.-needle.
Parents also reported more satisfaction and less anxiety after having received
specific information and preparation preoperatively. It was concluded that this
preoperative preparation programme is useful in all age groups with regard to
information, while alleviation of anxiety and fear was seen mainly among the
younger children with previous experience of anaesthesia.
PMID- 11012951
TI - Parental presence during anaesthesia induction for outpatient surgery of the
infant.
AB - We conducted a randomized controlled trial of parental presence during
anaesthesia induction for outpatient surgery in 73 infants (aged 1-12 months).
Effects of parental presence on infant and parental outcomes, including anxiety,
health care attitudes and satisfaction with the anaesthesia and surgery
experience were evaluated. Results demonstrated that parental presence had no
impact on infant behavioural distress during induction. In addition, parents who
were present demonstrated comparable anxiety levels and health care attitudes
before and after surgery, as well as comparable levels of satisfaction with the
surgical experience compared to parents who were absent during induction. We
discuss reasons for the lack of treatment effects from parental presence, and new
directions for future research to identify subgroups of children who may most
benefit from the opportunity to have parents involved in the perioperative
period.
PMID- 11012952
TI - The time-course of action and recovery of rocuronium 0.3 mg x kg(-1) in infants
and children during halothane anaesthesia measured with acceleromyography.
AB - This study compares the time-course of action of neuromuscular paralysis after
0.3 mg x kg(-1) of rocuronium during nitrous oxide-halothane anaesthesia in
children of three different age groups. With appropriate approval and informed
consent from the parents, 51 children, ASA I-II, scheduled for elective surgery
requiring muscle relaxation, were studied. The children were assigned to three
groups according to age: group 1, 0-6 months; group 2, 6-24 months; and group 3,
> 24 months of age. Induction of anaesthesia and tracheal intubation were
performed under halothane anaesthesia. Acceleromyography of the thumb was
recorded after supramaximal transcutaneous ulnar nerve stimulation using train-of
four (TOF) stimulation. Rocuronium 0.3 mg x kg(-1) was given as a rapid i.v.
bolus prior to surgical incision. The onset time (time to max effect) and the
maximal depth of the block, the time to recovery of the first twitch (T1) to 25%
and 75% of its baseline, the recovery index (RI), and the time to recovery of the
TOF ratio to 70% after the end of injection of rocuronium were all measured. The
mean (SD) age of the children in groups 1, 2, and 3 was 3.1 (1.6), 12.6 (3.7),
and 63 (46) months, respectively. The onset time of rocuronium was 47 (12), 83
(42) and 94 (12) s, respectively, in groups 1, 2, and 3 (P<0.05 group 1 vs. 2 and
3). One hundred percent block was achieved in 18/19 patients in group 1, 12/14 in
group 2 and 6/18 in group 3. The times to 25% and 75% recovery of T1 and the time
for recovery of the TOF ratio to 70% were all significantly longer in groups 1
and 2 compared to group 3. Group 1 and 2 showed no significant differences in
recovery times. The RI was significantly prolonged in group 1 versus 3. The
authors conclude that rocuronium 0.3 mg x kg(-1) during halothane anaesthesia
causes more neuromuscular depression and has a longer duration of action in
infants than in children older than 2 years.
PMID- 11012953
TI - Comparison of ropivacaine 0.1% and 0.2% with bupivacaine 0.2% for single-shot
caudal anaesthesia in children.
AB - We compared analgesic efficacy and degree of motor block induced by ropivacaine
0.1% (R 0.1) and 0.2% (R 0.2) vs. bupivacaine 0.2% (B 0. 2) after caudal
anaesthesia in children. Total and free plasma concentrations were measured after
caudal injection. Duration of caudal analgesia (median/range) was significantly
shorter in group R 0.1 (1.7 h/0.2-6 h) than in group R 0.2 (4.5 h/1.7-6 h) or
group B 0. 2 (4 h/1-6 h) (P<0.05). Motor block in the first 2 h postoperatively
was significantly less for both ropivacaine groups compared with bupivacaine
(P<0.05). Peak plasma concentrations after ropivacaine 0.2% were higher and
protein binding lower than after bupivacaine 0.2% (P<0.05). We conclude that
caudal analgesia with ropivacaine 0.1% is less effective and of shorter duration
than that of ropivacaine 0.2%, whereas ropivacaine 0.2% provides pain relief
similar to bupivacaine 0.2%. Motor block in the early postoperative period is
less with ropivacaine than with bupivacaine.
PMID- 11012954
TI - Comparison of three techniques for internal jugular vein cannulation in infants.
AB - Central venous cannulation allows accurate monitoring of right atrial pressure
and infusion of drugs during the anaesthetic management of infants undergoing
cardiopulmonary bypass. In this prospective, randomized study, we compared the
success and speed of cannulation of the internal jugular vein in 45 infants
weighing less than 10 kg using three modes of identification: auditory signals
from internal ultrasound (SmartNeedle, SM), external ultrasound imaging (Imaging
Method, IM) and the traditional palpation of the carotid pulsation and other
landmarks (Landmarks Method, LM). The cannulation time, number of attempts with
LM and SM techniques were greater than those with IM technique. The incidence of
carotid artery puncture and the success rate were not significantly different
among the three groups. In infants, a method based on visual ultrasound
identification (IM) of the internal jugular vein is more precise and efficient
than methods based on auditory (SM) and tactile perception (LM).
PMID- 11012955
TI - Anaesthesia with midazolam and S-(+)-ketamine in spontaneously breathing
paediatric patients during magnetic resonance imaging.
AB - We evaluated safety and efficacy of a sedation technique based on rectal and
intravenous S-(+)-ketamine and midazolam to achieve immobilization during
Magnetic Resonance Imaging (MRI). Thirty-four paediatric patients were randomly
assigned to undergo either the sedation protocol (study group) or general
anaesthesia (control group). Imaging was successfully completed in all children.
Children in the study group received a rectal bolus (0.5 mg x kg(-1) midazolam
and 5 mg x kg(-1) S-(+)-ketamine) and required additional i.v. supplementation
(20+/-10 microg x kg(-1) x min(-1) S-(+)-ketamine and 4+/-2 microg x kg(-1) x
min(-1) midazolam), spontaneous ventilation was maintained. Transient
desaturation occurred once during sedation and four times in the control group
(P=0.34). PECO2 was 5.3+/-0.5 kPa (40+/-4 mm Hg) in the study group and 4.1+/-0.6
kPa (31+/-5 mm Hg) in the control group (P<0.001). Induction and discharge times
were shorter in the study group (P<0.001), recovery times did not differ
significantly between the groups. Our study confirms that a combination of rectal
and supplemental intravenous S-(+)-ketamine plus midazolam is a safe and useful
alternative to general anaesthesia for MRI in selected paediatric patients.
PMID- 11012956
TI - Analgesic efficacy of ketorolac 0.5% ophthalmic solution (Accular) in paediatric
strabismus surgery.
AB - This prospective double-blind study was designed to assess the analgesic efficacy
of ketorolac 0.5% ophthalmic solution compared with placebo in 30 healthy
children undergoing extraocular muscle recession for correction of strabismus.
After paracetamol 20 mg.kg-1 preoperatively, a standard anaesthetic was given.
There were no significant differences in Children's Hospital of Eastern Ontario
Pain Scale (CHEOPS) and faces pain scale (FPS) scores, requirement for
supplementary analgesia or in postoperative vomiting between the two groups over
the following 24 h. This study did not demonstrate improved postoperative
analgesia when topical ketorolac eye drops were given in addition to paracetamol.
This observed lack of efficacy may reflect difficulties in the use of CHEOPS and
FPS in this age group with this pain model.
PMID- 11012957
TI - Percutaneous central venous catheterization in small infants: axillary block can
facilitate the insertion rate.
AB - Central venous cannulation through a peripheral vein is the technique of choice
in awake nonsedated critically ill infants. Such a technique has a high failure
rate. We undertook a retrospective study to determine whether a brachial plexus
block performed via the axillary approach could improve the success rate for the
insertion of a central venous catheter from a peripheral vein of the upper limb
in small infants. Data from 128 infants, submitted or not submitted to the
axillary block, were analysed. The failure rate for insertion of the central
venous catheter was 27% in the group without the use of the axillary block and 9%
with the axillary block (P<0.05). The use of brachial plexus block via the
axillary route, although evaluated retrospectively, improves the success rate for
the insertion of small diameter central venous silicon catheter from a peripheral
vein of the upper limb in small infants.
PMID- 11012959
TI - Parental opinions regarding the route of administration of analgesic medication
in children.
AB - Parents were asked about the acceptability of different routes of administration
of analgesia for their children. Their opinions were also sought regarding the
need for consent and of the sources and quality of information provided to them
perioperatively. Questionnaires before and after surgery were administered to 150
consecutively recruited parents. The majority (58%) of parents considered the
rectal route to be the most unpleasant way of giving medication, compared to 19%
for intramuscular and 11% and 9% for intravenous and oral, respectively. Over 70%
thought additional consent, either verbal or written, is not necessary for
administering medication by any route. The best information was received verbally
in the opinion of 90%. Contrary to expectations, the rectal route was the most
unpopular of all in this study. Parents' limited knowledge and experience may be
important determining factors. Despite their negative opinions, parents did not
consider separate consent necessary for the rectal or any other route.
PMID- 11012958
TI - The feasibility of pain treatment at home after adenoidectomy with ketoprofen
tablets in small children.
AB - In this study, we investigated the feasibility of pain treatment using ketoprofen
25 mg tablets (5 mg x kg(-1) x day(-1)) at home in children after daycase
adenoidectomy. We also determined the adverse events and the incidence of
postoperative bleeding during the first week after surgery. Initially, we studied
611 children aged 1-9 years. The study design was prospective, longitudinal, and
open. The final data consisted of 555 (91%) children, and 522 children who
received ketoprofen at home. The parents administered four (1-10, median with
10th and 90th percentiles) ketoprofen tablets to their children during the first
week. A total of 20% of the parents experienced problems in administering
tablets, and problems were three times more common in children under 48 months
compared to older children. The main problems were swallowing difficulties and
the unpleasant taste of the tablet. Neither serious adverse events, nor
clinically significant bleeding occurred. Ketoprofen at the dose of 5 mg x kg(-1)
x day(-1) proved to be a safe analgesic in children for short-term use after
adenoidectomy.
PMID- 11012960
TI - Anaesthetic management of children with congenital insensitivity to pain with
anhidrosis.
AB - Congenital insensitivity to pain with anhidrosis (CIPA) is a rare sensory
neuropathy, which affects patients' pain sensation and thermoregulation. There
are several issues to consider when planning anaesthesia for those with this
congenital disorder. Over a 20-year period, six patients with CIPA underwent 20
surgical procedures under general anaesthesia in our institution. We analysed our
experience with these patients retrospectively. We conclude that patients with
CIPA are able to undergo surgical procedures under general anaesthesia without
major problems.
PMID- 11012961
TI - The topics of international publications on paediatric anaesthesia from 1993 to
1998.
AB - A comprehensive compilation of the current international literature on paediatric
anaesthesia is still lacking. It was the aim of this study to identify all
publications with a focus on paediatric anaesthesia, and to determine the
spectrum of topics, as well as the publication type and language for the period
between 1993 and 1998. All articles published in 12 major anaesthesia journals
were evaluated and, additionally, a computerized, Internet-based Medline-search
was performed using selected keywords. The analysis was limited to original
articles, case reports, reviews and editorials. For the period between 1993 and
1998, a total of 2259 (377 per year) publications on paediatric anaesthesia were
identified in 295 different journals, the majority of which were on the topic of
'providing anaesthesia' in children (n=1424, 63.0%). In contrast, publications
on, for example, 'postanaesthesia care' (6. 3%), and 'organizational aspects of
paediatric anaesthesia' (2.2%) were rare. Most articles were written in English
(85.1%), and more than 50% reported original data (57.1%). Our results suggest
that several topics may be of interest for future research and communication in
the field of paediatric anaesthesia and new results should be published in
English to reach a large international readership.
PMID- 11012962
TI - Protein concentration in pulmonary oedema fluid for negative pressure pulmonary
oedema in children.
AB - We report a case of acute pulmonary oedema following upper airway obstruction in
a 1-year-old patient. We discuss the pathophysiology of this infrequent
complication of upper airway obstruction and the interest of alveolar
protein/blood protein ratio measurement to determine the mechanism of pulmonary
oedema.
PMID- 11012963
TI - Pseudopolyp of the right laryngeal ventricle following atraumatic intubation: a
diagnostic dilemma.
AB - The traumatic effects of tracheal intubation are well recognized. Whilst these
usually follow prolonged intubation, acute lesions have been described, usually
following a traumatic intubation technique. We present a case of acute, localized
swelling of the right laryngeal ventricle which followed an entirely atraumatic
intubation by an experienced paediatric anaesthetist. The lesion was not present
at the time of intubation, but developed subsequently during the surgical
procedure. Although previously observed at our institution, such lesions have not
been described in the literature. The potential for a diagnostic pitfall, by
mistaking the lesion for a laryngeal cyst or nodule, is discussed.
PMID- 11012964
TI - Inadvertent administration of intravenous ropivacaine in a child.
AB - Following abdominal surgery with inhalation anaesthesia and epidural ropivacaine
analgesia, inadvertent intravenous (i.v.) administration of ropivacaine occurred
in a 1-year-old boy. The child spent 75 min in the postanaesthesia care unit and
was transferred to the paediatric intensive care unit. Two hours after transfer,
it was noted that the epidural tubing was connected to the peripheral i.v. line.
The child remained awake, vital signs were stable, and his oxygen saturation
ranged from 96-98% on room air. The epidural catheter was removed. He did not
require further pain relief for the next 10 h.
PMID- 11012965
TI - Positive test dose in a neonate with a caudally placed epidural catheter.
AB - We present a case of a neonate with an epidural catheter placed via the caudal
route after induction of general anaesthesia in whom the test doses of
epinephrine-containing local anaesthetic was positive on two occasions.
Remarkable tachycardia was noted after each of two separate injections through
the catheter. Blood was never aspirated from the catheter and placement was
without difficulty. After the catheter was removed, blood was noted at the tip.
PMID- 11012966
TI - Train of four fade in a child with stiff baby syndrome.
AB - A case is described of a child with stiff baby syndrome who underwent open
reduction and femoral shortening of congenital dislocated hip under general
anaesthesia. Neuromuscular function was measured electromyographically and
demonstrated a great degree of train of four fade (57%) after sevoflurane
inhalational induction of anaesthesia. The response to suxamethonium (2 mg x kg(
1)) was normal. The neuromuscular response to volatile anaesthetic agents and
suxamethonium may be abnormal in these children with stiff baby syndrome and
intraoperative neuromuscular monitoring is recommended.
PMID- 11012967
TI - Anaesthetic management of erythropoietic protoporphyria.
PMID- 11012968
TI - Novel use of neonatal cuffed tracheal tube to occlude tracheo-oesophageal
fistula.
PMID- 11012969
TI - Authors' reply
PMID- 11012970
TI - Thumbs up for a new epidural catheter clamp!
PMID- 11012971
TI - Horner syndrome due to thoracic epidural analgesia in children.
PMID- 11012972
TI - Spinal anaesthesia in infants and children.
PMID- 11012973
TI - Echinococcus granulosus: assays for hydatid immunoregulatory factors using
established lymphoid cell lines.
AB - Mitosis, mitochondrial metabolic rate and proliferation were measured in
established lymphoid cell lines exposed to chromatographic fractions of equine
Echinococcus granulosus hydatid fluid. In several cell lines, one or more of the
three parameters were modified by the exposure. As an assay for potential
immunoregulatory activity, the method was simple and repeatable. The following
novel observations were made: (1) Mitotic reaction was found among lines of T
cell, B-cell and macrophage origin; (2) mitosis was accompanied by proliferation
in the B-cell lines, B9 and A20, and in the macrophage lines, HL-60 and P388d.
With mitotically responsive T-cells, proliferation was slight in CTLL-2 and
absent in D10, implying cell-cycle modification; (3) mitotic responsiveness
tended to occur in cell lines with mature characteristics; (4) among cytokine
dependent cell lines, hydatid fluid FPLC fraction 1 mimicked IL-1 and several
fractions mimicked IL-2 and IL-6 in the maintenance of mitosis; and (5) there was
significant statistical interaction between the influences of mammalian cytokines
and hydatid fluid fractions, implying that the propensity of antigenically
unprimed lymphoid cells to be regulated by E. granulosus is conditioned by
cytokine activity.
PMID- 11012974
TI - Interleukin-5 deficient mice exhibit impaired host defence against challenge
Trichinella spiralis infections.
AB - Enteric nematode infections are characterized by both peripheral and tissue
eosinophilia. The cytokine interleukin (IL)-5 is considered a critical factor in
the proliferation and recruitment of eosinophils, however, studies suggest it
plays little role in host defence, at least during primary Trichinella spiralis
infections. Less is known concerning its role in host defence or in the
inflammatory response that develops against challenge infections with the same
parasite. We examined these questions by infecting IL-5 deficient and wild-type
mice, with T. spiralis parasites. Both strains expelled the primary infection by
day 21. Forty days after the primary infection, we challenged the mice with a
second T. spiralis infection and counted tissue eosinophils and worms in the
intestine. While wild-type mice developed a large tissue eosinophilia, IL-5
deficient mice showed little increase in eosinophil numbers within the intestine.
Throughout the challenge infection, significantly larger worm burdens were
recovered from IL-5 deficient mice, and worm expulsion was also significantly
slower (day 21) compared to wild-type mice (day 14). Thus, unlike in a primary
infection, IL-5 is not only essential for the onset of intestinal eosinophilia,
but also makes a significant contribution to enteric host defence during
challenge T. spiralis infections.
PMID- 11012975
TI - The roles of the glycosylphosphatidylinositol anchor on the production and
immunogenicity of recombinant ookinete surface antigen Pbs21 of Plasmodium
berghei when prepared in a baculovirus expression system.
AB - Malarial ookinetes express an immunodominant surface protein (P28) that is a
priority candidate for the development of transmission-blocking vaccines. The
full length P28 gene from Plasmodium berghei [Pbs21(1-213)] and a deletion
construct [Pbs21(1-188)] encoding a protein that lacks the 25 C-terminal amino
acids, including the glycosylphosphatidylinositol (GPI) anchor signal, were
expressed in insect cells using baculovirus vectors. Pbs21(1-213) protein is
strongly hydrophobic, found in the cytoplasm and on the surface of Spodoptera
Sf21 cells, and in the culture medium. Pbs21(1-188) protein was largely found in
the aqueous phase of the medium and in the cytoplasm of Sf21 cells, but was not
detected on the cell surface. The presence of 25 C-terminal amino acids is
therefore critical to the attachment of recombinant Pbs21 to the parasite plasma
membrane. Mice were immunized subcutaneously or intramuscularly with affinity
purified recombinant Pbs21(1-213), Pbs21(1-188) or native Pbs21 proteins.
Following two immunizations, native Pbs21 induces higher titres when administered
by either route, than the recombinant protein bearing an insect GPI anchor, which
in turn is markedly more immunogenic than the recombinant polypeptide lacking a
GPI anchor. When specific anti Pbs21 antibody titres exceeded 1 mg/ml all three
antigens were capable of inducing transmission blockade > or = 90%, below 1 mg/ml
blockade did not correlate with antibody concentration.
PMID- 11012977
TI - Evidence for determining parasitic factors in addition to host genetics and
immune status in the outcome of murine Leishmania infantum visceral
leishmaniasis.
AB - C.B-17 SCID and congenic BALB/C mice were used to examine Leishmania infantum
strain pathogenicity independently of host genetic factors. While parasite loads
were significantly higher in immunodeficient mice than in immunocompetent mice,
the kinetics of infection during a long-term follow-up were similar, suggesting
that intrinsic parasitic factors also influence the outcome of L. infantum
infection.
PMID- 11012976
TI - HLA-A*0201 restricted CD8+ T-lymphocyte responses to malaria: identification of
new Plasmodium falciparum epitopes by IFN-gamma ELISPOT.
AB - The role of antigen specific CD8+ T-lymphocytes in mediating protection against
sporozoite-induced malaria has been well established in murine models. In humans,
indirect evidence has accumulated suggesting a similar protective role for
antigen-specific CD8+ T-lymphocytes. Nevertheless, the low frequency of
circulating specific cells together with the lack of sensitive methods to
quantify them has hampered the direct assessment of their function. Using a
combination of short-term cell culture and IFN-gamma ELISPOT, we studied CD8+ T
lymphocyte responses to a panel of HLA-A*0201 binding peptides. In addition to
confirming the response to already described epitopes, we also identified five
new CD8+ T-lymphocyte epitopes. These epitopes are presented in pre-erythrocytic
stages gene products of Plasmodium falciparum 7G8 strain and correspond to the
following protein segments: circumsporozoite (CS) 64-72, 104-113, 299-308 and 403
411; liver stage antigen (LSA-1) repeat region; sporozoite surface protein 2 or
thrombospondin related anonymous protein (SSP2/TRAP) 78-88 and 504-513. Four of
these peptides are conserved amongst all published sequences of P. falciparum
strains. We conclude that the modified IFN-gamma ELISPOT assay is a sensitive
technique to monitor antigen-specific CD8+ T-lymphocyte responses in human
malaria which may help in the improvement and assessment of the efficacy of
malaria subunit vaccines.
PMID- 11012979
TI - Proteolytic activity of cysteine protease in excretory-secretory product of
Paragonimus westermani newly excysted metacercariae pivotally regulates IL-8
production of human eosinophils.
AB - This study investigated the effect of the excretory-secretory product (ESP) of
Paragonimus westermani newly excysted metacercariae (PwNEM) on IL-8 production of
human mature eosinophils. Treatment of eosinophils with lower concentrations (0.3
and 1 microg/ml) of the ESP significantly (P < 0.01) induced IL-8 production,
whereas treatment of cells with higher concentrations (3 and 10 microg/ml) did
not. This effect of the ESP was concentration-dependent. Interestingly, the
amount of IL-8 production released into the culture supernatants was inversely
correlated with the rate of eosinophil survival. When eosinophils were cultured
with the same concentrations of the ESP for 24 h, the ESP resulted in eosinophil
death in a dose-dependent manner. To investigate whether high proteolytic
activity of proteases in the ESP could cause little production of IL-8, 10
microg/ml of ESP was pretreated with heat at 100 degrees C for 10 min or 56
degrees C for 30 min to reduce its proteolytic activity. IL-8 production of
eosinophils incubated with heat-treated ESP was markedly increased comparable to
that of cells treated with the lowest concentration used in this study. These
findings suggest that the protease in the ESP of PwNEM pivotally regulates IL-8
production by controlling of eosinophil survival, depending on the amount of ESP
released in vivo. Thus, the cysteine protease in the ESP of PwNEM could provide a
novel role to control recruitment of inflammatory cells in larval-infected
lesions in human paragonimiasis.
PMID- 11012978
TI - The 14-3-3 protein is secreted by the adult worm of Echinococcus granulosus.
AB - The 14-3-3 protein, already described in the metacestode of Echinococcus
multilocularis, has been characterized in the Echinococcus granulosus adult worm.
Immunolocalization studies show the presence of the 14-3-3 protein in the
periphery of testes and externally associated with the apical rostellum and
adjacent worm tegument. The alcian blue staining in consecutive parasite sections
gave similar reactivity patterns, suggesting that the 14-3-3 protein is produced
and secreted by rostellar glands. Immunoblot analysis showed the presence of the
14-3-3 protein in somatic and excretory-secretory worm products with higher and
smaller apparent molecular masses, respectively, than those detected in E.
multilocularis or E. granulosus metacestode tissues. Conversely, the 14-3-3
protein was not detected in metacestode secretory products. Detection of anti-E.
granulosus 14-3-3 reactivity in sera of experimentally infected dogs was achieved
at early stages of infection. Specific antibody titres decreased during the
course of infection. The possible origin and functions of the 14-3-3 protein
produced by the adult worm are discussed.
PMID- 11012980
TI - Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection
from it by Brazilian propolis and artepillin C.
AB - The protective effect of Brazilian propolis and its extract Artepillin C against
ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation and
carcinogenesis was studied in male ddY mice. Fe-NTA-induced renal lipid
peroxidation leads to a high incidence of renal cell carcinoma (RCC) in mice.
Administration of propolis by gastric intubation 2 h before or Artepillin C at
either the same time, 2 h, or 5 h before the intraperitoneal injection of Fe-NTA
(7 mg Fe/kg) effectively inhibited renal lipid peroxidation. This was evaluated
from the measurement of renal thiobarbituric acid-reactive substances (TBARS) or
histochemical findings of 4-hydroxy-2-nonenal (4-HNE)-modified proteins and 8
hydroxy-2'-deoxyguanosine (8-OHdG). Repeated injection of Fe-NTA (10 mg Fe/kg per
day, twice a week for a total of 16 times in 8 weeks) caused subacute
nephrotoxicity as revealed by necrosis and pleomorphic large nuclear cells in the
renal proximal tubules, and gave rise to RCC 12 months later. A protective effect
from carcinogenicity was observed in mice given propolis or Artepillin C.
Furthermore, the mice given Fe-NTA only developed multiple cysts composed of
precancerous lesions with multilayered and proliferating large atypical cells.
Mice treated with propolis and Artepillin C also had cysts, but these were
dilated and composed of flat cells. These results suggest that propolis and
Artepillin C prevent oxidative renal damage and the carcinogenesis induced by Fe
NTA in mice.
PMID- 11012982
TI - The world health organization classification of malignant lymphomas in japan:
incidence of recently recognized entities. Lymphoma Study Group of Japanese
Pathologists.
AB - New insights into the immunology and genetics of malignant lymphomas have allowed
the recognition of new entities and the refinement of previously recognized
disease categories. The relative incidence of these subtypes of malignant
lymphoma is also known to differ according to geographic location. In order to
clarify the current status of malignant lymphomas in Japan and the relative
incidences of their subtypes, 3194 patients were classified according to the new
World Health Organization (WHO) classification. Among these were 3025 cases
(94.71%) of non-Hodgkin's lymphoma (2189 cases (68.53%) of B-cell lymphoma, 796
cases (24.92%) of T-cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma.
The incidences of the major subtypes of non-Hodgkin's lymphoma were 33.34% for
diffuse large B-cell lymphoma, 8.45% for marginal zone B-cell lymphoma of mucosa
associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for
adult T-cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for
peripheral T-cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma,
2.6% for nasal and nasal-type T/NK cell lymphoma, 2.35% for angioimmunoblastic T
cell lymphoma, and 2.35% for precursor B-cell lymphoblastic leukemia/lymphoma, in
decreasing order. The other subtypes comprised less than 2%, mainly precursor T
cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large-cell lymphoma of T
and null-cell types (1.53%), and B-cell chronic lymphocytic leukemia/small
lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high
percentage (19.20%) in the south-western Japanese island, Kyushu, an endemic area
of human T-cell leukemia virus type 1 (HTLV-1), but which appeared to be lower
than that in a previous study. The nodular sclerosis and mixed cellularity types
of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are
distinct from those in Western countries and similar in several ways to those in
the East, although the relatively high rate of ATLL was attributed to the
geographical difference in the etiologic factor, HTLV-1.
PMID- 11012981
TI - Microsatellite instability and alteration of E2F-4 gene in adenosquamous and
squamous cell carcinomas of the stomach.
AB - Microsatellite instability (MSI) due to defective DNA mismatch repair (MMR) is a
form of genomic instability underlying the tumorigenesis of various human
neoplasms. To evaluate the roles of MSI in the pathogenesis of gastric carcinomas
with squamous differentiation, 17 primary stomach cancer patients (15
adenosquamous and two squamous cell carcinomas) were examined for MSI frequency
using five microsatellite markers and the criteria for MSI recommended by the
National Cancer Institute Workshop. The molecular causes and consequences of MSI
in these neoplasms were further researched through the immunohistochemistry of
MMR proteins and the mutational analysis of cancer-associated genes targeted by
MSI, respectively. Two of the 17 (12%) cases demonstrated MSI at the most
examined loci and were classified as having high level MSI (MSI-H). These tumors
also exhibited frame-shift mutations at mononucleotide repeats in the target
genes, including TGFbetaRII, IGFIIR, BAX, and hMSH6. It is interesting to note
that the mutations of the serine (AGC)13 repeats within the E2F-4 gene were found
only in the squamous cell carcinoma portions of them, whereas such alterations
were not detected in any of the adenocarcinomatous portions. This suggests that
E2F-4 might be implicated in the transformation of adenocarcinoma into squamous
cell carcinoma and further studies are needed to understand its role in squamous
differentiation.
PMID- 11012983
TI - Clinicopathological study of pleomorphic xanthoastrocytoma: correlation between
histological features and prognosis.
AB - The correlation between histopathological characteristics and prognosis was
studied in six cases of pleomorphic xanthoastrocytomas (PXA) found in five
patients. With regard to the duration from onset to the resection of the tumor,
and the postoperative course, three cases had a favorable prognosis, although one
case fatally recurred and in another, serial CT showed rapid tumor growth for 3
years. The histological characteristics of the favorable group of PXA comprised
remarkable degeneration, low mitotic activity and a low MIB-1 labeling index. In
contrast, the characteristics of the latter two cases of PXA rarely showed
degeneration, had atypical mitoses, increasing mitotic activity and a higher MIB
1 labeling index, which indicates that the findings of degeneration, atypical
mitoses, mitotic activity and MIB-1 labeling index correlate with the biological
behavior of PXA. However, with regard to histological appearance and clinical
course, PXA are tumors with a wide range of biological behavior.
PMID- 11012984
TI - Immunohistochemical inactivation of p14ARF concomitant with MDM2 overexpression
inversely correlates with p53 overexpression in oral squamous cell carcinoma.
AB - The CDKN2 gene encodes two structurally different proteins: a cyclin-dependent
kinase inhibitor called p16, which regulates retinoblastoma protein (pRb)
dependent G1 arrest, and a cell cycle inhibitor designated p14ARF, which arrests
cell growth in G1-S and also in G2-M. Whereas inactivation of p16 has been
described as a frequent event in various cancers, including oral cancer, the
current function of p14ARF is still poorly understood. A physical association
between p14ARF and MDM2 blocks MDM2-induced p53 degradation, resulting in
increased levels of p53, which in turn leads to cell cycle arrest. The present
study immunohistochemically examined the expression of p16 and p14ARF together
with pRb, MDM2 and p53 status in a series of oral cancers. The results showed
that p14ARF was frequently absent in the oral cancers (15/37, 41%) as was p16
immunostaining. Concomitant immunopositivity for p14ARF and MDM2 overexpression
was frequently observed in a subset of the cancers, whereas an inverse
correlation between p14ARF and MDM2 expression and the diffuse staining of p53
was clearly detected. Moreover, the results showed that in most cases of oral
cancer (35/37, 95%) at least one protein was altered, and lymph node metastasis
was more frequent in the tumors with alterations in both the p16/pRb and
p14ARF/p53 pathway (8/16, 50%) than in the tumors with one or no alteration of
these two major pathways.
PMID- 11012985
TI - Correlation of tumor markers p53, bcl-2 and cathepsin-D with clinicopathologic
features and disease-free survival in laryngeal squamous cell carcinoma.
AB - Various recognized prognostic factors in squamous cell carcinoma (SCC) of the
larynx influence the therapeutic options offered to an individual patient in
order to extend the survival expectancy. Additional prognostic indicators are
required in specific patient subgroups. The present study used a standard
immunohistochemical technique in order to retrospectively evaluate the
accumulation of p53 gene product and the immunoreactivity of bcl-2 protein and
cathepsin-D as possible prognostic markers of laryngeal SCC. Formalin-fixed,
paraffin-embedded tumor materials were obtained from a series of 64 patients with
cancer of the larynx. Immunostaining was evaluated by computerized image
analysis. The accumulation of p53 protein was found in 57.8% (37/64) of the
patients and was associated with large tumor size. The percentage of p53-positive
neoplastic cells increased in high-grade carcinomas, particularly when they
simultaneously demonstrated cathepsin-D immunoreaction in stromal cells (P =
0.049); bcl-2 immunoexpression was found to be generally limited. Cathepsin-D
immunostaining was observed in tumor parenchymal and stromal cells (31.25% and
37.5% of all cases, respectively); it was found to be useful in defining patient
subgroups with differences in relapse-free survival. Among patients with posi
tive lymph nodes, those with cathepsin-D immunopositive tumor cells were at
higher risk for relapsing (P = 0.0395). Although the classical prognostic factors
of laryngeal carcinoma retain their predominance, cathepsin-D immunoreactivity
may serve as an additional prognosticator in specific patient subgroups.
PMID- 11012986
TI - beta-catenin expression and mutational analysis in renal cell carcinomas.
AB - beta-Catenin acts as a downstream transcriptional activator of the Wingless-Wnt
signaling pathway. The beta-catenin-Tcf complex transactivates the downstream
genes that regulate cell proliferation or inhibit apoptosis. The activation of
this pathway through stabilization of beta-catenin is caused either by
inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene
or by activating mutations in beta-catenin exon 3. To determine whether the
abnormal expression and activating mutations in exon 3 of the beta-catenin gene
are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were
analyzed by immunohistochemistry, polymerase chain reaction-single-strand
conformational polymorphism analysis (PCR-SSCP), and direct DNA sequencing.
Immunohistochemically, all cases, as well as normal kidneys, showed membranous
and/or cytoplasmic staining patterns without nuclear localization. However, the
cytoplasmic accumulations of beta-catenin were observed in five (22.7%) of 22
cases of conventional (clear cell) renal carcinoma, but not in papillary or
chromophobe renal carcinomas. The beta-catenin mutation was identified in only
one case of conventional renal carcinoma and was a single-base missense mutation
on codon 61, leading to substitution of glutamine by arginine. In conclusion,
this study demonstrates that beta-catenin mutations are a relatively rare event
in RCC and that cytoplasmic accumulations of beta-catenin protein are found only
in conventional (clear cell) renal carcinomas. These data suggest that the
activation of the beta-catenin signaling pathway may partly play a role in the
development of conventional RCC.
PMID- 11012987
TI - Angiomatoid (malignant) fibrous histiocytoma: a peculiar low-grade tumor showing
immunophenotypic heterogeneity and ultrastructural variations.
AB - To clarify the cellular differentiation features and facilitate diagnosis of
angiomatoid (malignant) fibrous histiocytoma (AFH), four cases of AFH were
examined by clinicopathologic, immunohistochemical and ultrastructural analyses.
The age of the patients ranged from 10 to 24 years (mean, 17 years) and the sex
distribution was equal. All cases were of subcutaneous origin: three arose in the
trunk and one in the upper extremity. All patients presented with systemic
symptoms, including inflammatory signs and anemia. After a mean follow up of 11
years 3 months, all patients were alive and well, although one patient twice
developed local recurrence after surgery. All cases presented as multinodular,
cystic and hemorrhagic tumors ranging in size from 4 to 11 cm (mean, 8 cm) and
were characterized by sheets of bland spindle or round cells with oval nuclei
within a circumscribed nodule often surrounded by a lymphocytic cuff. One tumor
showed predominantly round cell morphology similar to Ewing's sarcoma/primitive
neuroectodermal tumor. All cases (100%) exhibited immunoreactivity for vimentin,
desmin, CD68 and CD57 (Leu-7). Three cases (75%) were positive for synaptophysin,
and reactivity for alpha-smooth muscle actin, epithelial membrane antigen, neuron
specific enolase and CD99 (O-13) was present in two cases (50%) each. The three
cases examined by electron microscopy had a mixture of fibrohistiocytic,
myofibroblastic and undifferentiated cells containing cytoplasmic processes and
dense-core granules. It is important for accurate diagnosis of this peculiar soft
tissue tumor to recognize that it has a variety of immunophenotypes, such as
histiocytic, myofibroblastic, epithelial and neural, and may occasionally have a
predominantly round cell morphology.
PMID- 11012988
TI - Pigmented villonodular synovitis secondary to laceration of the perforating
branch of the peroneal artery.
AB - A case of peroneal artery injury subsequently developed into a lesion resembling
an extra-articular tenosynovial giant cell tumor, which is a type of pigmented
villonodular synovitis (PVNS). This case supports the hypothesis that accident
trauma, such as a vascular injury, can be the etiology of PVNS.
PMID- 11012989
TI - Desmoplastic cerebral astrocytoma of infancy intermingling with atypical glial
cells.
AB - Despite the rarity of desmoplastic cerebral astrocytoma of infancy (DCAI), it has
distinct clinical and pathological features. The present case is a typical DCAI
except for its detection and operational age and intermingling with pleomorphic
glial cells. In this case, although a cystic lesion of the right temporal lobe
was noticed when the patient was 6 months old, it was not regarded as a tumor and
wasn't removed until he was 9 years old. It is quite unusual that a DCAI was able
to exist in the cerebrum for 9 years. However, no metastasis occurred and
distinct macroscopic and microscopic features of the tumor were not different
from typical DCAI except for an intermingling with pleomorphic glial cells.
Furthermore, even in the pleomorphic areas, the absence of necrosis and an MIB-1
index of 2.9% indicated non-aggressive growth. These features of the present case
may provide additional information as to the character of DCAI, which generally
has a favorable prognosis.
PMID- 11012990
TI - Lymphoid hyperplasia of the large intestine: a case report with
immunohistochemical and gene analysis.
AB - A case of lymphoid hyperplasia arising in the large intestine of a 54-year-old
woman is described. Barium enema X-ray and colonoscopic examination revealed
multiple small polyps in the right side of the colon. Pathological findings from
forceps biopsy revealed similar features to a mucosa-associated lymphoid tissue
(MALT) lymphoma. A right hemicolectomy with mesenteric lymph node dissection was
carried out. Histological sectioning demonstrated hypertrophic lymphoid follicles
with well-formed germinal centers. Occasionally, lymphocytes infiltrated the
crypts, in a way similar to that found in lymphoepithelial lesions, which was
suggestive of a MALT lymphoma diagnosis. Cryptitis was also observed in the
lamina propria. Immunohistochemically, proliferating lymphocytes were positive
for CD20 (L26) and negative for CD45RO (UCHL-1). Analyses of immunoglobulin gene
(IgHJH) rearrangement could not detect any monoclonality in these cells. These
findings suggested that the present case should be categorized as lymphoid
hyperplasia rather than lymphoma.
PMID- 11012991
TI - Hepatoid variant of yolk sac tumor of the testis.
AB - A case of testicular yolk sac tumor (endodermal sinus tumor) consisting
predominantly of hepatoid cells is documented. A mass measuring approximately 4 x
3 cm was noted in the left testis of a 64-year-old man. Preoperative examination
revealed an elevated serum level of alpha-fetoprotein (5479 ng/mL).
Histologically, the lesion was composed predominantly of sheet-like or trabecular
proliferation of hepatocyte-like cells with eosinophilic or clear cytoplasm. The
tumor cells were immunoreactive for alpha-fetoprotein, antimitochondrial
antibody, cytokeratin (AE1/AE3), alpha-1-antichymotrypsin, alpha-1-antitrypsin,
albumin, carcinoembryonic antigen and epithelial membrane antigen. It was
necessary to distinguish this variant lesion from metastatic hepatocellular
carcinoma, embryonal carcinoma and hepatoid carcinoma.
PMID- 11012993
TI - A new era? Back to the future, again.
PMID- 11012992
TI - Mesenchymal dysplasia of the placenta.
AB - A severe case of placental mesenchymal dysplasia occurred in association with
intrauterine fetal death (IUFD). The gravida-1, para-1 mother was a 26-year-old
Japanese. The first pregnancy was unremarkable and a healthy female infant was
delivered. The present pregnancy had been uneventful until 34 weeks of gestation
when IUFD was detected. The 1516-g (mean +/- SD, 2050 +/- 387 g) stillborn infant
had no external abnormalities and the karyotype was 46,XX. The placenta was
markedly enlarged (1050 g; mean +/- SD, 452 +/- 202 g), and approximately 80% was
occupied by extraordinary enlarged villous structures with a myxoid appearance.
Histologically, the dysplastic villi had myxoid stroma and a decreased number of,
occasionally obliterated, fetal vessels. There was no abnormal trophoblastic
proliferation. Large-sized fetal vessels in the chorionic plate frequently
contained organized thrombi. This is the first case of placental mesenchymal
dysplasia, which possibly lead to the IUFD.
PMID- 11012994
TI - Implementation of the Zuluaga-Raysmith (Z-R) model for assessment of perceived
basic human needs in home health clients and caregivers.
AB - The Zuluaga-Raysmith (Z-R) model is a conceptual framework that incorporates
accepted concepts of universal basic human needs developed by Maslow, yet removes
the hierarchical nature of these. The Z-R model recognizes the existence of a
health-illness continuum and accepts that an entity (individual, family,
aggregate, or community) may move freely in the direction of greater health and
self-actualization or towards illness and premature death. The Z-R model
identifies 10 basic needs and recognizes that a perceived deficit in any one of
these needs can adversely affect the level of wellness of the entity being
considered. This exploratory and descriptive study used 11 nurses as
interviewers. Subjects consisted of a convenience sample of homebound clients of
a home health agency in a metropolitan city, and selected caregivers (n = 27). A
modified functional wellness inventory (developed in 1993 by Louvenia Carter) was
used with several open-ended questions, which together related to the 10 needs of
the Z-R model. Reliability coefficient of the instrument was 0.84. Descriptive
statistics were used to analyze the data, using means, percentages, and
frequencies. Open-ended questions were grouped according to content and ranked in
order of frequency. The five most pressing needs of this small sample were
income; physical health; opportunity to make a contribution; mobility; and
mental, emotional, social, and spiritual health (MESSH). Nurses unanimously
reported that use of the instrument and the Z-R model helped them to focus on the
total person, identify strengths in their clients, identify perceived needs
deficits, and therefore, with the client, facilitate the preparation of a timely
and cost-effective interdisciplinary plan of care to help the entity to move to a
higher level of wellness despite the presence of chronic disease, disability, or
impending death. These findings suggested that further research is warranted to
explore the use of the Z-R model. A replication study is in progress.
PMID- 11012995
TI - Cost analyses of home care and nursing home services in the southern Taiwan area.
AB - This study compares the cost of long-term care provided at patient homes with
that of long-term care provided in nursing homes in southern Taiwan. Caring for a
patient with a high degree of dependence at home is more expensive than caring
for a patient in a nursing home facility when family costs and provider costs are
considered together. This phenomenon is not demonstrated for patients with medium
degrees of dependence. To be cost-effective, home care services should target
patients with medium physical disability, and nursing home care should focus on
patients with high levels of dependence.
PMID- 11012996
TI - The crisis nature of health care transitions for rural older adults.
AB - The complex health, socioeconomic, and environmental problems experienced by many
American elders often place them at high risk for disease and disability. Over
time, acutely or chronically ill older persons experience numerous transitions
across various health care settings. Although availability of health services is
improving in rural areas, barriers such as distance, geography, and poor
distribution often limit access to health care. In a longitudinal rural
ethnography, the health care transition experiences of older adults, families,
and health care providers were examined. A major ethnographic theme emerged from
analysis data from interviews, participant observations, and photographs: the
crisis nature of health care transitions experienced by rural older adults and
their families and observed by rural nurses and other health care providers.
Several patterns were observed including the crisis was compounded by surprise;
limited knowledge of local resources exacerbated the crisis; inconsistent
discharge planning disrupted transitions; changing family support necessitated
admission to nursing homes; continuity of care in nursing home discharge lessened
transition crisis; and rural home health care was identified as a strength.
Recommendations were made for community-based interventions to improve the
transition experience. Comprehensive care management services provided by public
health nurses (PHNs) in the local rural community were recommended.
PMID- 11012997
TI - Extending the extended family for homeless and marginally housed African American
women.
AB - Young homeless African American women and elderly marginally housed African
American women have health, housing, and personal concerns specific to their age
cohort, yet they also have parallel and complementary needs. The young struggle
to find affordable housing, while the old may have difficulty in maintaining
their homes. This article reports select findings from a pilot study designed to
describe these two groups of women. The preliminary study was conducted
preparatory to the development of a larger study to explore factors that would
facilitate or hinder linking the two groups of women for mutual assistance in
housesharing arrangements. Interviews and housing history findings revealed
contrasts and similarities among the women and between both cohorts that
reflected individual differences, common yet divergent life courses, and
collective responses to family life situations, societal trends, and policies.
Advantages and disadvantages of housesharing were delineated with 56.3% of the
homeless women and 81.3% of the elderly women viewing coresidential living as an
option worth considering. Housesharing arrangements should be further
investigated by nurses and colleagues. Findings from this study are foundational
for establishing alliances that may be a means to promote health and strengthen
"family" in both populations.
PMID- 11012998
TI - Missouri rural adolescent pregnancy project (MORAPP).
AB - The purpose of this study was to investigate the pregnancy outcomes and services
available to adolescent women in Missouri, comparing rural and urban residents. A
secondary analysis of a large public use data set obtained from the Missouri
Department of Health was done for the 5-year period 1992 to 1996. Data were
collected by county, with each of the 114 counties of the state classified as
rural or urban. The SAS program was used for analysis. Results demonstrated
definite patterns of similarity and dissimilarity among the teen mothers based on
residence, when age and race were controlled. There were over 54,000 births to
adolescent mothers in the 5-year study period. Among the outcomes of pregnancy
studied were: abortion rates, inadequate weight gain, intrauterine growth
retardation, and low-birthweight (LBW) infants. Among the services available to
the young mothers that were studied were fertility services, WIC (women, infants,
and children supplemental nutrition) program, food stamps, and Medicaid coverage
for pregnancy and infant care. The outcomes are probably generalizable to
Midwestern, rural/urban states similar to Missouri.
PMID- 11012999
TI - A substance use prevention framework: considering the social context for African
American girls.
AB - Shifting patterns of substance use (that is, early initiation, increased
marijuana use, narrowing differences in gender use) and the disproportionate
socioeconomic obstacles that are related to substance use among ethnically
diverse adolescent females create the need to develop ethnic and gender-specific
substance use prevention frameworks. This article describes and applies a
substance use prevention framework to African American females. Gender
socialization and self-efficacy are presented as key concepts, along with the
assertion that every substance use prevention framework should examine the
influences of specific societal factors (such as racism, sexism, classism, and
ageism) on substance use. Rationale and guidelines for designing ethnically
sensitive and gender-specific research projects and intervention programs
regarding substance use prevention are offered. Public health nurses (PHNs) are
uniquely positioned to use this framework in their work with African American
adolescent girls, specifically, and in general with other ethnically diverse
groups.
PMID- 11013001
TI - The clinical specialist in community health nursing: a solution for the 21st
century.
AB - The clinical specialist (CS) in community health nursing (CHN) addresses health
problems in populations and communities in ways that are different from and
complimentary to strategies used by practitioners of individualized patient care.
Four programs based on comprehensive assessments, systematic program planning,
deliberate implementation, and both formative and summative evaluation are
presented. The programs were developed by graduate students in the CHN clinical
specialization major at the Frances Payne Bolton School of Nursing. With expert
faculty guidance and a competency-driven program of study, strategies were
implemented to promote the health of community-dwelling well elderly people, home
health care nurses who provide service to patients with respiratory problems, and
high school students in a private religious school. Experienced parish nurses
also benefited from a program designed to enhance their skills in theological
reflection. This article also describes the curricular design developed to
educate this clinician for the 21st century. Lastly, continued attention to the
dynamic criteria of the American Nurses Association Standards of Community Health
Nursing Practice is recommended as crucial to the further development of this
clinical specialization.
PMID- 11013000
TI - Community resiliency: the potential for community health nursing theory
development.
AB - There is insufficient theory development within community health nursing that
addresses the community as a collective and not simply as groupings of
aggregates. Conceptual clarification of nursing's domains is needed, however,
before theory development can take place. In an attempt to rectify this
situation, this article discusses the environment domain. Community resiliency,
or the ability of a community to deal with adversity and in so doing reach a
higher level of functioning, is presented as a useful framework to gain greater
understanding of this particular domain. Findings from research that have
resulted in a community resiliency model for describing the environment domain,
within which rural-based community health nurses (CHNs) work, are presented. The
relevance for community health nursing theory is included with recommendations
for future research and subsequent theory development.
PMID- 11013002
TI - Health protecting and health promoting behaviors of African Americans living in
Appalachia.
AB - The importance of the influence of health protecting and health promoting
behaviors on the health of Appalachian African Americans has not been widely
published. Review of the literature revealed a paucity of research data
describing these behaviors. Therefore, the purpose of this descriptive study was
to describe health protecting and health promoting behaviors of Appalachian
African Americans. Pender's (1996) health promotion conceptual framework was used
as the organizing framework for this study. Data were collected through
structured interviews with 204 Appalachian African Americans representing two
states and six counties in Appalachia. Quantitative research methodology was used
to describe health protecting and health promoting behaviors. Data analysis
revealed that these participants actively engaged in health protecting and health
promoting behaviors. Morbidity data, mortality data, and family history of
diseases were consistent with those reported nationally. Findings from this study
support the need for a long-range research study of Appalachian African
Americans.
PMID- 11013003
TI - Osteoporosis education programs: changing knowledge and behaviors.
AB - Osteoporosis is an age related metabolic disease that primarily affects women and
causes bone demineralization that results in fractures. Early identification of
risk factors for osteoporosis and development of prevention programs is needed to
halt the increasing incidence of the disease. Public health nurses (PHNs), with
their emphasis on primary, secondary, and tertiary prevention with individuals
and families, are in a unique position to protect the health of these vulnerable
populations who are at risk for osteoporosis. This article describes the
implementation and program evaluation of three osteoporosis prevention
educational programs that use three levels of intensity of design. Each design is
based upon the learning needs of the targeted audience. The goals of each program
were to increase knowledge of osteoporosis, increase health beliefs, and increase
the frequency of osteoporosis preventing behaviors. Theoretical aspects from
adult learning and the Health Belief Model (HBM) were used to develop the
programs. For the program evaluation, participants completed evaluation
instruments before and 3 weeks after participating in an osteoporosis health
education program. Participants in all programs had significantly higher levels
of knowledge after completing the programs; however, overall, there was no change
in health beliefs or behaviors. Implications of these findings are discussed.
PMID- 11013004
TI - Molecular analysis of human immunoglobulin heavy chain variable region associated
determinants recognized by anti-VH3 antibodies 7B4, B6 and D12.
AB - 7B4, B6 and D12 are murine monoclonal antibodies (MoAb) that bind to some human
immunoglobulin heavy chain products of the closely related V3-30, V3-30.3 and V3
33 genes from the VH3 family. B6 and D12 have additional reactivities with some
immunoglobulins (Ig) encoded by the V3-11 and V3-7 genes; D12 also reacts with
some V3-43 gene Ig. We show here, by site-directed mutagensis, that the lysine at
position 57 in the complementarity-determining region 2 (CDR-2) of the V3-30 gene
product is crucial for epitope recognition by all three anti-VH3 MoAbs. Further
analysis of the amino-acid sequences of a large panel of Ig reactive, or
nonreactive, with MoAb 7B4 indicates that the determinant recognized by 7B4 is
dependent on the presence of the tetrapeptide sequence NKYY between positions 56
and 59 in the CDR-2. Comparing the efficiency of 7B4 reactivity with VH3 gene
encoded human Ig indicates that amino-acid position 4 in the frame region 1 (FR
1) may also influence the binding of 7B4 to Ig encoded by three very closely
related germline genes, V3-30, V3-30.3 and V3-33. NKYY is also found on the gp120
V3 region of human immunodeficiency virus (HIV)-2, SIV and HTLV-4. We also report
that other tetrapeptide sequences found on the 56-59 motif of heavy chain
variable regions encoded by germline genes are expressed on the solvent exposed
V2 region of gp120 of HIV-1 isolates. The possible significance of these
observations is discussed.
PMID- 11013005
TI - Protective effect of Plantago major L. Pectin polysaccharide against systemic
Streptococcus pneumoniae infection in mice.
AB - The antibacterial effect of a soluble pectin polysaccharide, PMII, isolated from
the leaves of Plantago major, was examined in inbred NIH/OlaHsd and Fox Chase
SCID mice experimentally infected with Streptococcus pneumoniae serotype 6B.
Serotype 6B is known to give a more protracted infection when injected
intraperitoneally into susceptible mice than more virulent serotypes like type 4.
PMII was administered i.p. either once 3 days before challenge or once to thrice
from 3 to 48 h after challenge. The number of bacteria in blood and the mouse
survival rate were recorded. Pre-challenge administration of PMII and also
lipopolysaccharide (LPS), included as a control, gave a dose-dependent protective
effect against S. pneumoniae type 6B infection. However, injection of PMII after
establishment of the infection in NIH/OlaHsd mice had no effect. The data
demonstrate that, firstly, the polysaccharide fraction PMII from P. major
protects against pneumococcal infection in mice when administered systemically
prechallenge, and secondly that the protective effect is owing to stimulation of
the innate and not the adaptive immune system.
PMID- 11013006
TI - Splenectomy and adoptive cell transfer reveal a prominent role for splenic memory
lymphocytes in the development of chronic relapsing experimental autoimmune
encephalomyelitis.
AB - We previously reported that acute experimental autoimmune encephalomyelitis
(EAE), induced by active immunization of SJL mice, could be converted into
chronic relapsing EAE (CR-EAE) by a pretreatment with neuroantigen and killed
mycobacteria 2 months earlier. This finding indicates that immune memory,
established by the pretreatment, influences the subsequent EAE induction. The
present study shows that splenectomy and lymphadenectomy, applied 1 week before
the subsequent active immunization of the pretreated mice, efficiently abort the
chronic nature of CR-EAE. Furthermore, we have found that adoptive transfer of
lymphocytes from the spleen (but not of those from the local draining lymph
nodes) of the pretreated mice to naive syngeneic recipients 1 week before the
acute EAE-induction immunization results in the development of CR-EAE. On the
other hand, the transfer of lymphocytes from the local draining lymph nodes
aggravates the acute disease. These data support a critical role for immune
memory of the previous suboptimal challenge in the development of chronic
relapsing demyelinating disease.
PMID- 11013007
TI - Neutrophil response of transgenic mice expressing human group IIA phospholipase
A2 in bacterial infections.
AB - Group IIA phospholipase A2 (PLA2) is a newly recognized acute phase protein with
marked antibacterial properties. We have shown previously that transgenic C57BL/6
J mice expressing human group IIA PLA2 (PLA2+ mice) are more resistant to
bacterial infections than nontransgenic C57BL/6 J mice that, among mice, are
unusual in that they lack the mouse analogue of group IIA PLA2 (PLA2- mice). To
elucidate the possible mechanisms involved in the host response of these mice in
bacterial infection, peripheral inflammatory cell responses of PLA2+ and PLA2-
mice were studied after i.p. administration of Escherichia coli, E. coli
lipopolysaccharide or Staphylococcus aureus. Uninfected PLA2+ mice had higher
numbers of lymphocytes and polymorphonuclear neutrophil leukocytes (PMNs) in
their blood than PLA2- mice. In PLA2+ mice, the number of PMNs increased in
peripheral blood in parallel with the concentration of group IIA PLA2 after the
administration of bacteria, whereas these responses were not seen in PLA2- mice.
High concentrations of group IIA PLA2 in PLA2+ mice may increase the synthesis of
bioactive molecules, such as prostaglandins, which in turn may mobilize PMNs into
circulation. Our results support the hypothesis that group IIA PLA2 is an
important inflammatory mediator in bacterial infections.
PMID- 11013008
TI - Hypersusceptibility of A/J mice to tuberculosis is in part due to a deficiency of
the fifth complement component (C5).
AB - Mycobacterium tuberculosis (MTB) causes tuberculosis in man, which occurs as an
acute, chronic or dormant disease reactivating over several years. The mechanisms
of persistence and reactivation are not well understood and there is a need for
animal models. Moderate-dose, aerosol infection killed A/J mice earlier than
partially resistant C57Bl/6 mice, whereas a low-dose, aerosol-induced chronic
infection exacerbated earlier in A/J mice. A/J mice lethally infected with MTB
but drug cured of disease underwent reactivation of tuberculosis at least 100
days before similarly infected C57Bl/6 mice. Because A/J mice were C5 deficient,
congenic B10 mice sufficient and deficient for C5 were infected intravenously
with MTB to define the role of C5. C5-deficient mice again showed enhanced growth
of MTB in the lungs. MTB-infected macrophages from C5-deficient mice showed
enhanced growth of MTB coinciding with a reduced secretion of both cytokines (TNF
alpha, IL-1beta, IL-6, IL-12) and chemokines (KC, MIP-2 and MIP-1alpha) in A/J
and TNF-alpha and chemokines in C5-deficient mice. Because C5-deficient
macrophages could be activated from extraneous C5 and TNF-alpha we suggest that
both play a role in the macrophage-mediated killing as well as containment
mechanisms in tuberculosis.
PMID- 11013009
TI - The Vdelta1 T cell receptor repertoire in human nasal mucosa.
AB - The gamma/delta T cells play important roles as the first line of defence in
mucosal immunity. Vdelta1 bearing T cells comprise the major population of
gamma/delta T cells in the human nasal mucosa. Recently, it was reported that
certain receptors are predominant at given anatomical locations. The purpose of
this study was to elucidate the gamma/delta T-cell receptor repertoire in human
nasal mucosa. Nasal epithelia were scraped and peripheral blood were obtained
from three healthy volunteers. We performed reverse-transcription polymerase
chain reaction (RT-PCR) analysis and characterized the junctional sequences of
Vdelta1 T-cell receptor (TCR) transcripts. Vgamma and Vdelta gene usage in
intraepithelial lymphocytes (IELs) in right and left nasal mucosa were almost the
same, but they were different from those in peripheral blood lymphocytes (PBLs).
The VDJ sequence of nasal Vdelta1 T-cell receptor transcripts showed diversity
and were different for each individual. Vdelta1 in the IELs were rearranged to
Jdelta1 and Vdelta1 in the PBLs were rearranged not only to Jdelta1 but also to
Jdelta3. Vdelta1 sequences in the IELs in the nasal mucosa showed no overlap with
those in the PBLs. These results indicate that gamma/delta T cells in the nose
are organ specific lymphocytes.
PMID- 11013010
TI - Down-regulation of interleukin-12, interleukin-12R expression/activity mediates
the switch from Th1 to Th2 granuloma response during murine Schistosomiasis
mansoni.
AB - In murine schistosomiasis mansoni the worm egg-induced granulomatous inflammation
is bi-phasic: an initial Th1 type is subsequently switched to a Th2 type
response. Analysis of the cellular, molecular base of the Th1-associated response
(5-6 weeks post infection) revealed mRNA messages for interleukin (IL)-12 p40, IL
12Rbeta2 and interferon (IFN)-gamma in the granulomatous livers. When the Th2
type granulomas matured (8 weeks post infection) message expression weakened or
became extinct. Macrophages of the Th1 type granulomas produced maximal amounts
of IL-12, but production diminished in the mature granulomas. A similar pattern
of IL-12 responsiveness of granuloma lymphocytes was observed. In vitro IL-12
production by Th1 type granuloma macrophages was enhanced by tumour necrosis
factor (TNF)-alpha and IFNgamma, whereas lymphocyte IL-12 responsiveness was
boosted only by TNF-alpha. Both systems were down-regulated by IL-4 and IL-10
cytokines. Treatment of mice with anti-IL-10 monoclonal antibodies (MoAb) between
6 and 7 weeks of the infection enhanced mRNA expression for IFN-gamma and IL
12Rbeta2, but not for IL-12 p40. It is concluded that IL-12 and IL-12R expression
and function regulate the Th1 phase of the liver granulomatous response. This
phase is cross-regulated by type-2 cytokines especially IL-10.
PMID- 11013011
TI - Tamoxifen decreases renal inflammation and alleviates disease severity in
autoimmune NZB/W F1 mice.
AB - It has been documented that sex hormone may play a role in the pathogenesis of
murine lupus. To determine the effect of tamoxifen (TAM) on NZB/W F1 female mice,
a total dose of 800 microg (22 mg/kg body weight) of TAM was administered
subcutaneously every 2 weeks. The control mice were injected with peanut oil
only. After treatment with TAM for 5 months, the mice were killed and
immunological parameters were evaluated. The results suggest that NZB/W F1 mice
treated with TAM had less severe proteinuria and increased survival rate compared
to controls. Flow cytometric analysis of splenocytes revealed a significantly
lower percentage of B cells and CD5+ B cells in the TAM-treated group. There was
a significantly lower serum level of soluble tumour necrosis factor (TNF)
receptor I and II molecules in the TAM-treated mice. Immunohistological study
showed that control mice had severe immune complex deposition in the kidney. In
contrast, TAM-treated mice had much less pathological change. In summary, this
study demonstrated that TAM treatment might be able to alleviate the symptoms of
lupus nephritis, influence B-cell count, modulate the expression of cytokine
receptors and thereby subsequently affect immune function. Further studies to
determine the cellular mechanisms in lupus nephritis may increase our
understanding of this complex disease and provide additional targets for
therapeutic intervention.
PMID- 11013012
TI - Analysis of the tissue distribution of the rat C5a receptor and inhibition of C5a
mediated effects through the use of two MoAbs.
AB - The C5-anaphylatoxin C5a is a protein of 74 (human) or 77 (rat) amino-acid
residues, respectively, the generation of which may be induced by either the
classical and/or the alternative pathways. C5a binds specifically to its receptor
(C5aR/CD88) which belongs to the superfamily of G-protein-coupled receptors with
seven transmembrane segments. In this study we describe the tissue distribution
of the rat C5aR (rC5aR) and the blocking of its ligand by the application of two
monoclonal antibodies (MoAbs). The first antibody (MoAb R63) which is directed
against the amino-terminal domain Ex1 of the rat C5aR was generated in mice
immunized with RBL-2H3 cells which had been stably transfected with the rat C5a
receptor gene. Checking the rC5aR expression in various tissues bronchial
epithelial cells stained positive only in tissue samples from animals with a
mycoplasm infection indicating that the receptor may be induced in this cell type
as a consequence of an inflammatory process. Using immunohistochemistry there was
no evidence for nonmyeloid expression in the large or small intestine, heart,
lung, kidney or liver of the normal rat. The MoAb R63 was found to be a reliable
tool for the investigation of the expression of the receptor by FACS analyses or
immunohistochemistry. Despite numerous attempts neutralizing antibodies could not
be generated against the receptor. Therefore a C5a-ligand neutralizing MoAb was
generated against the synthesized carboxyterminal 20mer peptide. This antibody (6
9F) recognized the carboxy terminus of C5a/C5a-FLUOS and prevented its binding at
a three-fold molar excess as evidenced by FACS-analyses. It also blocked the C5a
mediated signal transduction as demonstrated by the inhibition of intracellular
Ca2+-release (at a 16-fold molar excess) and the release of N-Acetyl-beta-D
glucosaminidase (at a 25-fold molar excess).
PMID- 11013013
TI - Detection of a soluble form of the complement membrane attack complex inhibitor
CD59 in plasma after acute myocardial infarction.
AB - Activation of the complement system has been documented in both experimental and
clinical studies of acute myocardial infarction (AMI). Our earlier
immunohistochemical studies have shown that the deposition of the membrane attack
complex (MAC) of complement is associated with the loss of protectin (CD59), a
glycosyl-phosphatidylinositol (GPI)-anchored sarcolemmal regulator of MAC, from
the human and rat infarcted myocardium. In this study we detected, using an
enzyme immunoassay (EIA), CD59 in the plasma of AMI patients at a concentration
of 23.0+/-8.4 ng/ml (mean +/- SD; n = 17) at 4 h and 27.3+/-11.8 ng/ml (n = 24)
at 24 h after AMI. Both values were significantly higher than in healthy controls
(7.8+/-6.4 ng/ml; n = 20; P<0.001). The amount of CD59 correlated with the level
of soluble terminal complement complexes (SC5b-9; r = 0.84; P<0.01) in the
plasmas of AMI patients. Our results suggest that myocardial damage leads to
release of CD59 from the sarcolemmal cell membranes during AMI.
PMID- 11013014
TI - The function of a journal.
PMID- 11013015
TI - An economic assessment of Apligraf (Graftskin) for the treatment of hard-to-heal
venous leg ulcers.
AB - Several recent advances in wound care may offer promise for the treatment of hard
to-heal venous leg ulcers. One such treatment is Apligraf (Graftskin), a
bilayered, living human skin construct. To assess the economic impact of
Graftskin, a model was constructed to compare the annual medical costs and cost
effectiveness of treating hard-to-heal venous leg ulcers with Graftskin vs.
compression therapy using Unna's boot. A semi-Markov model was used to describe
the pattern of ulcer treatment, healing, and recurrence among patients with
venous leg ulcers. Patients received 1 of 2 treatment regimens, Graftskin or
Unna's boot, and were followed in the model for a 12-month period. The analysis
was done from the perspective of a commercial health plan; therefore, only direct
medical costs were included. Health care resource use included the primary
therapeutic intervention, additional compression dressings, physician office
visits, home health visits, laboratory tests and procedures, management of
adverse events, and hospitalizations. The model estimated the annual medical cost
of managing patients with hard-to-heal venous leg ulcers to be $20,041 for those
treated with Graftskin and $27,493 for those treated with Unna's boot. In
addition, treatment with Graftskin led to approximately 3 more months in the
healed state per person per year than did treatment with Unna's boot. Because
patients treated with Graftskin experienced improved healing compared with those
treated with compression therapy using Unna's boot, they required fewer months of
treatment for unhealed ulcers. As a result, the use of Graftskin for treating
hard-to-heal venous leg ulcers resulted in lower overall treatment costs.
PMID- 11013016
TI - Randomized clinical trial of the effect of semi-occlusive dressings on the
microflora and clinical outcome of acute facial wounds.
AB - This study investigated whether treatment with occlusive, hydroactive
polyurethane dressings affects the microflora and clinical outcome of acute
wounds. A randomized, controlled trial was performed on 60 patients with acute
facial lacerations. Following primary closure, patients were provided with either
a dry-gauze dressing or a hydroactive polyurethane dressing (Cutinova Thin). The
wounds were assessed clinically and microbiologically prior to closure, then
after 5, 28 and 56 days. The dressing, which was removed at day 5, was also sent
for microbiological culture. Wounds treated with the polyurethane dressing showed
improved comfort and contour (p < 0.04), less erythema (p < 0.03) and less
potential for scarring (p < 0.01) at day 5. At day 28 and day 56, there were no
significant differences in the clinical assessment between the test and control
groups (p > 0.05). A total of 518 isolates were recovered from the patients
during the study. Mean number of isolates and bacterial growth density were
calculated in both groups. A similar range of microorganisms were obtained from
both treatment groups with no clear difference in organism colonization. This
study shows the potential usefulness of facial wounds as a human model for
studying acute wound healing responses and anti-scarring therapy. While short
term, clinical benefits of occlusive dressings were evident in the management of
acute wounds, these data clearly show that all studies of scarring following
acute wounding should extend over at least 3 months post-injury to allow for
spontaneous improvement to occur.
PMID- 11013017
TI - Simple biochemical markers to assess chronic wounds.
AB - We investigated the potential for the biochemical analysis of chronic wound fluid
to predict healing using simple and widely available analytes in an out-patient
clinic setting. Wound fluid was collected from 12 patients attending a leg ulcer
clinic and analyzed for a variety of analytes, including lactate, total protein,
and albumin. Twelve weeks after collection the wound was assessed for healing
(defined as complete healing or greater than 50% reduction in wound size). The
median total protein (44.3 +/- 8.8 g/l) and albumin (25.0 +/- 2.3 g/l)
concentrations in exudate collected from four healing wounds were significantly
higher (p < 0.05) than in exudate from eight nonhealing wounds (median total
protein 29.7 +/- 7.6 g/l, median albumin 17.0 +/- 4.3 g/l). No significant
difference was observed for lactate. A second specimen of wound fluid was
collected from four of the patients (three nonhealing and one healing). The
protein analysis confirmed the pattern observed for the first collection:
nonhealing wounds had total protein and albumin which remained low compared to
healing wounds. No wound with an exudate albumin of less than 20 g/l healed. Both
total protein and albumin are stable analytes which can be easily measured in any
laboratory and may offer a simple biomarker of healing in chronic wounds.
PMID- 11013018
TI - In vitro fibroblast populated collagen lattices are not good models of in vivo
clinical wound healing.
AB - In chronic wounds, the healing process is prolonged and incomplete, proceeding in
an uncoordinated manner, and resulting in poor anatomical and functional outcome.
There have been numerous attempts to discover models that mimic human wound
healing processes. The fibroblast populated collagen lattice is one such model
that has been proposed. This study evaluated whether the fibroblast populated
collagen lattice can be a model of chronic wound healing using the pressure ulcer
as a paradigm. Fibroblast cultures of wound biopsies and wound volume
measurements were obtained serially during a four arm blinded, placebo-controlled
sequential cytokine clinical trial of pressure ulcers. Fibroblasts obtained from
study patients were added to collagen lattices and contraction was determined
daily for 10 days. Collagen gel-area measurements were converted to reflect
percentage of gel contraction. These data of both edge and base wound biopsies on
days 0, 10, and 36 were categorized into treatment groups and one-way analysis of
variance showed no significant differences in contraction among these groups.
When considering all fibroblast populated collagen lattices, there was
significantly greater contraction at days 10 and 36 for cells from both edge and
base biopsies compared to day 0 (p < 0.05). The Spearman Rank Correlation test
comparing all patients with fibroblast populated collagen lattice results from
fibroblasts obtained at the edge or base of the wound at days 0, 10, and 36 and
clinical pressure ulcer healing on day 36 showed no correlation. This lack of
correlation not only persisted for each of the four treatment arms but also for
responder status based on decrease in wound volume over the 35 day trial period.
In conclusion, chronic wound healing is a complex process that is not modeled by
in vitro fibroblast populated collagen lattices.
PMID- 11013019
TI - Denervation retards but does not prevent toetip regeneration.
AB - Toetips of mammals regrow after amputation by a process similar, but not
identical, to that which occurs during regeneration of a newt limb. Nerve is
needed as a mitotic stimulant for newt limb regeneration but the requirement for
nerve during rodent digit-tip regeneration is not known. Nerve dependence in rats
was tested by severing the sciatic nerve in one hindlimb, amputating digit-tips
from the central digits of both hind feet, and comparing the amount of regrowth
in innervated and denervated digits. Denervation delayed soft-tissue wound
healing. However, denervation did not significantly affect bone regrowth when
animals were examined at one month. Because we suspected delayed bone regrowth,
we used a new method that we developed to follow bone growth at several time
points in each animal. Termed visible bone fluorescence through nail, this
technique used serial injections of fluorescent calcium-deposition markers and
observation through the toenails to observe bone growth in living animals. Using
this method it was possible to detect retarded bone regrowth in denervated
digits. Thus, although denervation of rodent tips delayed both soft tissue
healing and bone regrowth, it did not prevent ultimate restitution of the
amputated part. This suggests that neurotrophic stimulation in the mammalian
digit-tip is not identical to that documented during newt limb regeneration, and
that growth stimulation may be provided by tissues other than nerve.
PMID- 11013020
TI - Matrix metalloproteinase production in regenerating axolotl spinal cord.
AB - In urodele amphibian spinal cord regeneration, the ependymal cells lining the
central canal remodel the lesion site to favor axonal regrowth. We profiled the
production of matrix metalloproteinases by injury-reactive mesenchymal ependymal
cells in vivo and in vitro and found that matrix metalloproteinases are involved
in this remodeling process in the axolotl (Ambystoma mexicanum). The production
of cell-associated matrix metalloproteinases in vivo was shown to be identical to
that in our cultured ependymal cell model system. Activated and zymogen forms of
matrix metalloproteinases were identified using zymography, chemical inhibitors
of matrix metalloproteinases, and cleavage of propeptides by organomercurials.
The principal cellular proteinases consisted of matrix metalloproteinase-2
(gelatinase A) and matrix metalloproteinase-1 (type I collagenase), which display
characteristic shifts in molecular weight following proenzyme processing by
organomercurials. In addition, ependymal cell conditioned medium contained
secreted forms of the enzyme undetectable in situ. Matrix metalloproteinase-9
(gelatinase B) as well as matrix metalloproteinase-2 and matrix metalloproteinase
1 were secreted and casein substrate zymography showed the presence of a small
amount of a very high molecular weight matrix metalloproteinase-3
(prostromelysin) secreted into the culture medium. Matrix metalloproteinases were
still present at 4 weeks post-lesioning when the ependymal cells have just re
epithelialized, but decreased near the completion of regeneration (8 weeks post
lesioning). Zymography showed no detectable matrix metalloproteinases in
unlesioned cord but the presence of tissue inhibitor of metalloproteinase-1 in
intact cord was seen by Western blotting. This study shows that matrix
metalloproteinases are associated with urodele spinal cord regeneration and
validates the use of our ependymal cell tissue culture model system to evaluate
ependymal cell behavior during spinal cord regeneration.
PMID- 11013021
TI - Increase in wound breaking strength in rats in the presence of positively charged
dextran beads correlates with an increase in endogenous transforming growth
factor-beta1 and its receptor TGF-betaRI in close proximity to the wound.
AB - We have previously shown that positively charged beads (DEAE A25) increase wound
breaking strength in linear incisions in rats and nonhuman primates at days 10-14
post-wounding. The increased wound strength may result in part from a stimulation
of cells adjacent to the DEAE A25 beads to produce growth factors important for
wound healing. In this report, we investigate this hypothesis by comparing the
relative expression levels of transforming growth factor-beta1 and its receptor
transforming growth factor-beta receptor type I in DEAE A25-treated and
contralateral untreated rat linear incisions. DEAE A25-treated incisions were
stronger than untreated control wounds at 3 days post-wounding, and the
difference in breaking strength reached statistical significance at days 5, 7 and
10. Immunohistochemical analysis revealed a significant increase in transforming
growth factor-beta1 and transforming growth factor-beta receptor type I
expression in DEAE A25-treated incisions, up to 7 days post-wounding, as compared
to untreated control wounds. FACS analysis revealed that macrophage cell lines
exposed to DEAE A25 in vitro upregulate transforming growth factor-beta1 and
transforming growth factor-beta receptor type I expression by 2-3 fold.
Therefore, the increase in expression of transforming growth factor-beta1 and
transforming growth factor-beta receptor type I in DEAE A25-treated incisions may
be due to an increase in the concentration of macrophages adjacent to DEAE A25
beads, as well as the stimulation of individual macrophages to produce greater
amounts of transforming growth factor-beta1 and transforming growth factor-beta
receptor type I. This study also supports the significance of transforming growth
factor-beta1 in wound healing.
PMID- 11013022
TI - Development of a chronic skin defect model and a study of cytokine secretion
using the model.
AB - In this study, we established a delayed healing chronic type wound model in order
to investigate the etiology of chronic wound healing, including wound
contraction. Establishment of the model was important for clarification of the
mechanism(s) of chronic wound healing and wound contraction and for use in
evaluating therapeutic efficacy. A pedicled skin flap was raised beneath the
panniculus carnosus membrane on the backs of mice, and after the loose connective
tissue at the base of the flap was completely removed surgically, the flap was
replaced and sutured. Seven days after surgery, a full-thickness defect measuring
1.5 x 1.5 cm was made in the center of the skin flap. At that time, a defect of
the same size, including the panniculus carnosus membrane, was made in another
group of mice as controls, and changes with time in wound area were compared
between the two groups. The exudate retained on the wound surface was collected,
and various cytokines contained in the exudate were measured. In the control
group, the wound rapidly contracted and almost completely epithelialized and
closed 21 days after surgery. On the other hand, the wound area was significantly
larger in the delayed model than in the control animals during the observation
period, revealing a delay in wound contraction. Transforming growth factor-beta,
interleukin-1beta, and tumor necrosis factor-alpha in the exudates from the wound
of the model were significantly higher than in those of the control group,
whereas interleukin-6 was low in the model. From these results, it was concluded
that this model could be a useful experimental system for studies on wound
contraction as well as clarifying the mechanism of so called chronic type wounds.
PMID- 11013023
TI - Presidential address: where science touches man, it turns to art.
PMID- 11013024
TI - Is routine use of the intensive care unit after elective infrarenal abdominal
aortic aneurysm repair necessary?
AB - INTRODUCTION: Postoperative care after infrarenal abdominal aortic aneurysm (AAA)
repair has traditionally involved admission to the intensive care unit (ICU).
With the advent of endovascular AAA repair, the management of open procedures has
received increased scrutiny. We recently modified our AAA clinical pathway to
include selective use of the ICU. METHODS: Consecutive elective infrarenal AAA
repairs performed by members of the vascular surgery division at a university
medical center from 1994 to 1999 were analyzed retrospectively with a
computerized database, the Medical Archival Retrieval System. Group I consisted
of 245 patients who were treated in the ICU for 1 or more days, and Group II
included 69 patients admitted directly to the floor. Ruptured, symptomatic,
suprarenal, endovascular, and reoperative repairs were excluded. Outcome
variables were compared over the 6-year period. RESULTS: Floor admissions
increased over the study period with 0%, 0%, 3.3%, 16.3%, 48.6%, and 43.6% of
patients admitted directly to the surgery ward from 1994 to 1999. The average ICU
length of stay declined from 4.6 to 1.2 days, whereas the hospital length of stay
decreased from 12.5 to 6.8 days from 1994 to 1999. The change in ICU use had no
effect on death (2.4% in Group I vs 0% in Group II). Major and minor morbidity
was comparable. Hospital charges were significantly lower for patients in Group
II. CONCLUSION: A policy of selective utilization of the ICU after elective
infrarenal AAA repair is safe. It can reduce resource use without a negative
impact on the quality of care.
PMID- 11013025
TI - Carotid endarterectomy: the financial impact of practice changes.
AB - PURPOSE: New techniques in the management of extracranial carotid occlusive
disease have focused attention on the outcome and economics of carotid
endarterectomy (CEA). Changing practice patterns for CEA must be assessed to
allow accurate comparisons. The purpose of this study was to evaluate the effect
of practice modifications related to CEA on patient outcome and cost data.
METHODS: Data on patients undergoing CEAs at a single institution from fiscal
year 1992 to 1998 were prospectively collected and entered into a computerized
database. Records were reviewed for patient demographics and outcome with regard
to stroke and death. Selected years that corresponded to transitions in
perioperative management were audited for complete hospital financial information
from. RESULTS: We performed 960 CEAs during the study period, with a combined
stroke and death rate of 1.1%. Inflation-adjusted hospital costs per patient in
1998 dollars for the years 1992, 1996, and 1998 were $5494, $4476, and $3350,
respectively. In 1998, costs for patients who required arteriography were $1825
greater than those operated on during duplex scan examination alone in 1998.
Statistically significant differences occurred in the year-to-year comparisons in
the use of arteriography, intensive care unit monitoring, same day admissions,
and length of stay. There were no statistically significant differences in the
stroke and death rate between years. CONCLUSION: Practice changes related to CEA
have resulted in significant savings without detriment in patient outcome.
Comparisons between CEA and endovascular techniques will need to be evaluated
within this context. Given these advances in perioperative management, it will be
difficult to justify carotid stenting on the basis of current economic
considerations.
PMID- 11013026
TI - Cranial and cervical nerve injuries after repeat carotid endarterectomy.
AB - BACKGROUND AND PURPOSE: The incidence of cranial and/or cervical nerve injuries
after primary carotid endarterectomy (CEA) ranges from 3% to 48%; however, the
clinical outcome of these injuries after repeat CEA has not been thoroughly
analyzed in the English-language medical literature. This prospective study
analyzes the incidence and outcome of cranial nerve injuries after repeat CEA.
PATIENTS AND METHODS: This study includes 89 consecutive patients who had repeat
CEAs. Preoperative and postoperative cranial nerve evaluations were performed,
including clinical examinations (neurologic) and direct laryngoscopy. Patients
with vagal or glossopharyngeal nerve injuries also underwent comprehensive speech
evaluations, video stroboscopy, fluoroscopy, and methylene blue testing for
aspiration. Patients with postoperative cranial nerve injuries were followed up
for a long time to assess their recovery. RESULTS: Twenty-five cranial and/or
cervical nerve injuries were identified in 19 patients (21%). They included 8
hypoglossal nerves (9%), 11 vagal nerves or branches (12%) (6 recurrent laryngeal
nerves [7%], 3 superior laryngeal nerves [3%], and 2 complex vagal nerves [2%]),
3 marginal mandibular nerves (3%), 2 greater auricular nerves (2%), and 1
glossopharyngeal nerve (1%). Twenty-two (88%) of these injuries were transient
with a complete healing time ranging from 2 weeks to 28 months (18 of 22 injuries
healed within 12 months). The remaining three injuries (12%) were permanent (1
recurrent laryngeal nerve, 1 glossopharyngeal nerve, and 1 complex vagal nerve
injury). The recurrent laryngeal nerve injury had a longer healing time than the
other cranial nerve injuries. CONCLUSIONS: Repeat CEA is associated with a high
incidence of cranial and/or cervical nerve injuries, most of which are transient.
However, some of these have a long healing time, and a few can be permanent with
significant disability.
PMID- 11013027
TI - Use of shunts with eversion carotid endarterectomy.
AB - PURPOSE: The purpose of this study was to examine the utility of carotid shunting
in the context of eversion endarterectomy. A comparison of patients who underwent
carotid endarterectomy by eversion with and without shunts was performed.
METHODS: Over a 5-year period, 2724 eversion carotid endarterectomies were
performed. In most of these operations patients were under cervical block
anesthesia. A shunt was used in 112 eversion endarterectomies (4.1%). Cervical
block anesthesia was used in 103 patients (92.0%), general anesthesia was used in
5 patients (4.5%), and 4 patients (3.6%) were converted from cervical block to
general anesthesia intraoperatively. The indications for shunting were neurologic
deterioration in 99 patients (88.4%) who were under cervical block anesthesia,
procedures performed in neurologically unstable or otherwise compromised patients
who were under general anesthesia, and the operator's discretion in the remaining
eight patients. RESULTS: There was a combined stroke/death rate of 2.7% in the
shunt group. These three cases included one death from myocardial infarction and
one delayed death due to intracerebral hemorrhage after discharge. Shunt
insertion was unrelated to the negative outcome in these two cases. One
perioperative major stroke in the shunt group was identified. Follow-up averaged
12.3 months (range, 1-53 months). CONCLUSION: Carotid shunts can be used
effectively in the context of eversion endarterectomy. Shunt insertion is not
associated with an increased stroke/death rate in these patients.
PMID- 11013028
TI - Prevalence of deep venous reflux in patients with primary superficial vein
incompetence.
AB - PURPOSE: This prospective study was designed to determine the prevalence of deep
reflux and the conditions under which it may occur in patients with primary
superficial venous reflux and absence of deep venous thrombosis (DVT). METHODS:
We studied 152 limbs in 120 consecutive patients in the standing position who had
superficial venous reflux with color flow duplex scanning. Limbs with documented
evidence of DVT or post-thrombotic vein wall changes during the examination were
studied but not included in the analysis. Limbs were divided into those that had
at least reflux in the saphenofemoral, the saphenopopliteal, or the
gastropopliteal junction and into those with nonjunctional reflux in the
superficial and gastrocnemial veins. Peak velocity and duration of reflux were
measured. To examine the recirculation theory, we tested the deep veins by
occluding and refluxing saphenous veins 10 cm below the sampling site. RESULTS:
Thirteen limbs in 11 patients (9%) were excluded because of previous DVT. Of the
remaining 139 limbs, 106 (76%) had junctional reflux. Saphenofemoral junction was
involved in 89 limbs (84%), saphenopopliteal junction in 18 (17%), and
gastropopliteal junction in 7 (4%). In 33 limbs (24%), reflux was detected in the
main trunk or tributaries of the saphenous veins alone with no junctional
incompetence. Femoral or popliteal reflux was present in 31 limbs (22%). This
reflux was segmental in 27 limbs, and it was limited in the junction in 24 limbs.
The mean duration of deep venous reflux was 0.9 seconds, it ranged from 0.6 to
3.7 seconds, and it was significantly shorter than that in the superficial veins
(2.6 seconds; P <.0001). In the absence of junctional reflux, the prevalence of
deep venous insufficiency (DVI) was significantly lower compared with that in
limbs with junctional involvement (2 of 33 vs 29 of 106; P =.038). The mean
duration of deep venous reflux in these groups was comparable (0.85 seconds vs 0.
91 seconds; P =.44). Occlusion of the incompetent superficial veins reduced
somewhat the duration of the deep venous reflux but did not abolish it (0.88
seconds vs 0.82 seconds; P =.072). The presence of DVI was associated with
junctional reflux of high peak velocity and long duration. CONCLUSIONS: The
prevalence of DVI in patients with primary superficial venous reflux and without
history of DVT is 22%. However, this reflux is segmental, mainly in the common
femoral vein, and is of short duration. It is associated with the presence of
junctional incompetence that has a high peak velocity and long duration. These
findings may explain why surgical correction of superficial reflux abolishes DVI.
PMID- 11013029
TI - Prospective screening for postoperative deep venous thrombosis in patients
undergoing infrainguinal revascularization.
AB - PURPOSE: The incidence of deep venous thrombosis (DVT) in patients undergoing
infrainguinal bypass graft procedures has not been well documented, and the need
for routine prophylaxis remains controversial. The purpose of this study was to
prospectively evaluate the risk of postoperative DVT complicating infrainguinal
revascularization. METHODS: Seventy-four patients undergoing infrainguinal bypass
graft procedures during a 12-month period were prospectively screened for DVT.
Bilateral lower extremity venous duplex scan imaging was performed preoperatively
and within 1 week and 6 weeks, postoperatively. Routine DVT prophylaxis was not
used, with anticoagulation reserved for specific indications. RESULTS: Of the 74
patients screened, three patients (4.1%) had DVT identified on preoperative
venous duplex scan imaging and were excluded from the study. Of the remaining 71
patients enrolled, only two patients (2.8%) had postoperative DVT. Postoperative
DVT was ipsilateral to the bypass graft extremity in both patients, with
involvement of the peroneal vein in one patient and the femoral vein in the
other. Although routine prophylaxis was not used, 18 of these patients (25%) were
anticoagulated for other indications, with DVT occurring in one patient (5.6%).
Of the remaining 53 patients who did not receive postoperative anticoagulation,
only one patient (1.8%) had DVT. CONCLUSIONS: According to this prospective
study, the risk of postoperative DVT in patients undergoing infrainguinal
revascularization is low. Routine prophylaxis is not recommended, with
postoperative anticoagulation reserved for specific indications.
PMID- 11013030
TI - Adverse consequences of internal iliac artery occlusion during endovascular
repair of abdominal aortic aneurysms.
AB - OBJECTIVE: Embolization of the internal iliac artery (IIA) may be performed
during endovascular abdominal aortic aneurysm (AAA) repair if aneurysmal disease
of the common iliac artery precludes graft placement proximal to the IIA orifice.
The IIA may also be unintentionally occluded because of iliac trauma or coverage
by the endograft. The purpose of this study was to determine the incidence,
etiology, and consequences of IIA occlusion during endoluminal AAA repair.
METHODS: Over 2 years, 96 patients have undergone endoluminal AAA repair. The
details of the operative procedure, reasons for IIA occlusion, perioperative
complications, and clinical follow-up were recorded. RESULTS: The IIA was
intentionally occluded in 15 patients (16%) to treat 13 common iliac artery
aneurysms, one IIA aneurysm, and one external iliac artery aneurysm. The IIA was
unintentionally occluded in 9 patients (9%), resulting from traumatic iliac
dissection in 5 patients and coverage of the IIA by the endograft in the
remaining 4 patients. Three patients had colon ischemia. One patient with a
unilateral IIA occlusion had sigmoid infarction necessitating resection. The
other two patients underwent intentional occlusion of one IIA followed by
unintentional occlusion of the contralateral IIA because of a traumatic iliac
dissection. Both had postoperative abdominal pain and distention; rectosigmoid
ischemia was revealed through colonoscopy. Conservative treatment with bowel rest
and broad-spectrum antibiotics was successful in both cases. Nondisabling hip and
buttock claudication occurred in seven patients (32%) at 1 month but resolved by
6 months in three of these patients. CONCLUSION: Embolization of the IIA for
iliac aneurysmal disease and unintentional IIA occlusion due to trauma or graft
coverage occurs in a considerable number of patients undergoing endoluminal AAA
repair. Most patients with unilateral occlusion do not experience colon ischemia
or disabling claudication. Therefore, unilateral embolization of the IIA is well
tolerated and allows for the endoluminal treatment of patients with both an AAA
and an iliac artery aneurysm, thereby expanding the number of patients who can be
managed with an endovascular approach. Although acute, bilateral IIA occlusions
should be avoided, significant consequences were not observed in our small series
of patients.
PMID- 11013031
TI - Safety of coil embolization of the internal iliac artery in endovascular grafting
of abdominal aortic aneurysms.
AB - PURPOSE: During endovascular grafting of an abdominal aortic aneurysm (AAA),
iliac limb extension to the external iliac artery may be indicated when the
common iliac artery is ectatic or aneurysmal. Preliminary or concomitant coil
embolization of the internal iliac artery (IIA) is thus necessary to prevent
potential reflux and endoleak. We sought to determine the safety of hypogastric
flow interruption in this setting. METHODS: We retrospectively reviewed 156
patients who underwent stent-graft AAA repair at two institutions between
February 1, 1998, and January 31, 1999. Coil embolization of one or both IIAs was
undertaken when the diameter of the common iliac artery was more than 20 mm to
enable limb endograft extension to the external iliac artery. Bilateral
procedures were staged. RESULTS: Thirty-nine (25%) of 156 patients were selected
for coil embolization of one (n = 28) or both (n = 11) IIAs. The interventions
were performed before (n = 31) or during (n = 8) the stent-graft procedure.
Complications included groin hematomas in 3 patients, iliac artery dissection in
1, failure to catheterize the IIA in 2, and transient rise in the serum
creatinine level in 3. One patient had erectile dysfunction, and five patients
(13%) had buttock claudication after unilateral occlusion. Serious ischemic
complications were not observed. CONCLUSION: Coil embolization of one or both
IIAs appears to be safe in the setting of endovascular grafting of AAA. Buttock
claudication is a relatively significant problem and may limit applicability of
this strategy to patients who are unfit for standard open repair.
PMID- 11013032
TI - Long-term fate of the aneurysmal sac after endoluminal exclusion of abdominal
aortic aneurysms.
AB - PURPOSE: Shrinkage of an abdominal aortic aneurysm (AAA) is the hallmark of
successful endoluminal treatment. Our goal was to prospectively assess the
midterm to long-term shrinkage of the AAA sac after endovascular repair. METHODS:
A total of 123 patients with AAA underwent endoluminal treatment with the Ancure
device at our institution between February 1996 and February 2000. At least a 1
year follow-up was available for 70 of the 123 patients. AAA sac size, presence
of endoleaks, calcifications, and outcome data were collected on these patients
at 6, 12, 24, and 36 months after repair and compared with the preoperative AAA
size and characteristics. All endoleaks found at the 6-month follow-up visit were
treated aggressively with embolotherapy. An AAA sac regression of 0.5 cm or more
was considered the minimum measurable decrease. Regression of the sac diameter to
3.5 cm or less was considered a complete collapse of the sac. RESULTS: Successful
endoluminal repair was accomplished in 119 of 123 patients. The mortality rate
was 0.8% (1/123). There was a steady decrease in AAA sac size from baseline (5.56
+/- 0.1 cm), to 6 months (5.0 +/- 0.14 cm, P =.0006), to 12 months (4.65 +/- 0.13
cm, P =.04), and to 24 months (4.26 +/- 0.16 cm, P =.03). At 24 months, 74%
(29/39) had a decrease in sac size of 0.5 cm or more, with 28% (11/39) complete
collapse. Patients with initial endoleaks had the same likelihood of regression
of sac size (> or = 0.5 cm) when compared with the group of patients with no
endoleaks at the 24-month evaluation (64% vs 76%, P =.09). CONCLUSION:
Endoluminal AAA repair resulted in a significant reduction in sac size that
continues up to 2 years. Significant shrinkage occurs as early as 6 months after
placement. The initial presence of endoleaks does not predict the lack of sac
regression.
PMID- 11013033
TI - Transrenal fixation of aortic stent-grafts for the treatment of infrarenal aortic
aneurysmal disease.
AB - PURPOSE: We evaluated our early experience with the transrenal fixation of aortic
stent-grafts to determine the efficacy of this procedure and its effects on renal
artery patency and hemodynamics. METHODS: Twenty-eight patients (22 men) had
endoluminally placed modular bifurcated stent-grafts with a bare spring structure
at the proximal end crossing the origin of both renal arteries; no patient with
infrarenal fixation was included for analysis. The mean age of the patients was
75 +/- 7 years (range, 58-86 years); the mean aneurysm size was 5.8 +/- 0.8 cm
(range, 4.7-7.2 cm). Eight patients had preoperative or intraoperative
angiographic evidence of renal artery atherosclerotic disease, but only four
vessels had luminal narrowing of 50% or greater. No complications were noted
during stent-graft placement, and all patients have returned for follow-up
visits, ranging from 1 to 12 months (mean follow-up, 6 +/- 4 months). Follow-up
evaluations included clinical assessment, duplex ultrasound scan of the renal
arteries and kidneys, and computed tomographic angiography. RESULTS: No evidence
of lobular or sublobular perfusion defects of the renal parenchyma was detected
postoperatively. Two patients exhibited postoperative changes in renal artery
hemodynamics-one progressing from a 30% diameter reduction to a greater than 60%
diameter stenosis at the 12-month follow-up visit and one with a normal renal
artery preoperatively having elevated flow velocities indicative of a greater
than 60% stenosis at the 1-month visit. Of 19 patients with normal preoperative
renal function, only one has had persistently elevated serum creatinine levels.
CONCLUSION: We conclude from this experience that the transrenal placement of
open stents is safe and effectively excludes the aneurysm, potentially expanding
the availability of this technique to more patients with a short infrarenal
aortic neck. Long-term follow-up is essential to determine the overall efficacy
of this technique and to identify potential effects on renal artery hemodynamics
or kidney function.
PMID- 11013034
TI - Does the endovascular repair of aortoiliac aneurysms pose a radiation safety
hazard to vascular surgeons?
AB - OBJECTIVES: Endovascular aortoiliac aneurysm (EAIA) repair uses substantial
fluoroscopic guidance that requires considerable radiation exposure. Doses were
determined for a team of three vascular surgeons performing 47 consecutive EAIA
repairs over a 1-year period to determine whether this exposure constitutes a
radiation hazard. METHODS: Twenty-nine surgeon-made aortounifemoral devices and
18 bifurcated devices were used. Three surgeons wore dosimeters (1) on the waist,
under a lead apron; (2) on the waist, outside a lead apron; (3) on the collar;
and (4) on the left ring finger. Dosimeters were also placed around the operating
table and room to evaluate the patient, other personnel, and ambient doses.
Exposures were compared with standards of the International Commission on
Radiological Protection (ICRP). RESULTS: Total fluoroscopy time was 30.9 hours
(1852 minutes; mean, 39.4 minutes per case). Yearly total effective body doses
for all surgeons (under lead) were below the 20 mSv/y occupational exposure limit
of the ICRP. Outside lead doses for two surgeons approximated recommended limits.
Lead aprons attenuated 85% to 91% of the dose. Ring doses and calculated eye
doses were within the ICRP exposure limits. Patient skin doses averaged 360 mSv
per case (range, 120-860 mSv). The ambient (> 3 m from the source) operating room
dose was 1.06 mSv/y. CONCLUSIONS: Although the total effective body doses under
lead fell within established ICRP occupational exposure limits, they are not
negligible. Because radiation exposure is cumulative and endovascular procedures
are becoming more common, individuals performing these procedures must carefully
monitor their exposure. Our results indicate that a team of surgeons can perform
386 hours of fluoroscopy per year or 587 EAIA repairs per year and remain within
occupational exposure limits. Individuals who perform these procedures should
actively monitor their effective doses and educate personnel in methods for
reducing exposure.
PMID- 11013035
TI - Aortic fenestration for acute or chronic aortic dissection: an uncommon but
effective procedure.
AB - BACKGROUND: Aortic fenestration is rarely required for patients with acute or
chronic aortic dissection. To better define its role and the indications for its
use and to evaluate its success at relieving organ or limb malperfusion, we
reviewed our experience with direct fenestration of the aorta. METHODS: A
retrospective analysis of all consecutive aortic fenestrations performed between
January 1, 1979, and December 31, 1999, was performed. Fourteen patients, 12 men
and two women (mean age, 59.6 years; range, 43-81), underwent fenestration of the
aorta. All patients were hypertensive and had a history of tobacco use. By
Stanford classification, there were three type A and 11 type B patients. In the
acute dissection group (n = 7), indications for surgery were malperfusion in six
patients (leg ischemia, 4; renal ischemia, 5; bowel ischemia, 3) and intra
abdominal bleeding from rupture in two. In the chronic dissection group (n = 7),
indications for surgery were abdominal aortic aneurysm in 4 patients (infrarenal,
3; pararenal, 1), thoracoabdominal aneurysm in 1, hypertension from coarctation
of the thoracic aorta in 1, and aortic occlusion with disabling claudication in
1. RESULTS: Emergency aortic fenestration was performed in seven patients
(surgically for 6 and percutaneously for 1). Fenestration level was infrarenal in
four and pararenal in three. Concomitant abdominal aortic graft replacement was
performed in four patients, combined with ascending aortic replacement (n = 1)
and bilateral aortorenal bypasses (n = 1). In two patients, acute fenestration
was performed for organ malperfusion after prior proximal aortic replacement
(ascending aorta, 1; descending thoracic aorta, 1). Seven elective aortic
fenestrations were performed for chronic dissection (descending thoracic aorta,
2; paravisceral aorta, 2; infrarenal aorta, 2 and pararenal aorta, 1).
Concomitant aortic replacement was performed in six patients (abdominal aorta, 5;
thoracoabdominal aorta, 1). Fenestration was successful at restoring flow in all
10 patients with malperfusion. Operative mortality for emergency fenestration was
43% (3/7). The three deaths that occurred were of patients with anuria or bowel
ischemia, or both. There were no postoperative deaths for elective fenestration.
At a mean follow-up of 5.1 years, there were no recurrences of malperfusion and
no false aneurysm formations at the fenestration site. CONCLUSION: Fenestration
of the aorta can effectively relieve organ or limb ischemia. Bowel ischemia and
anuria are indicators of dismal prognosis and emergency fenestration in these
patients carries a high mortality. Elective fenestration combined with aortic
replacement can be performed safely in chronic dissection. Aortic fenestration is
indicated for carefully selected patients with malperfusion and offers durable
benefits.
PMID- 11013036
TI - Visceral pseudoaneurysms due to pancreatic pseudocysts: rare but lethal
complications of pancreatitis.
AB - OBJECTIVE: Erosion of pancreatic pseudocysts into adjacent vessels is a rare but
highly lethal cause of intra-abdominal hemorrhage. Percutaneous angiographic
embolization (PAE) of the bleeding artery has recently been advocated as the
preferred therapy. This study was undertaken to survey the outcome after
treatment of this complication and to make recommendations for its management.
METHODS: An 11-year retrospective analysis was performed of all patients treated
at a large tertiary care referral center for visceral artery pseudoaneurysms
associated with pancreatic pseudocysts. RESULTS: From 1988 to 1998, 256 patients
were admitted for complications of pancreatic pseudocysts. Sixteen patients (11
men and 5 women) were identified in whom a pseudocyst had eroded into a major
blood vessel with hemorrhage or development of a false aneurysm. The mean age was
45 years (range, 23-67 years). Active bleeding was present in 13 patients,
whereas three had evidence of recent hemorrhage. Ten of 16 patients initially
underwent operative therapy, four elective and six emergency, whereas six stable
patients were initially treated with PAE. Technical failures of the initial
treatment or secondary complications required both therapeutic modalities in six
patients, which resulted in 13 total surgical interventions and 10 PAEs. The
surgical morbidity rate was 62% (8 of 13), whereas that of PAE was 50% (5 of 10).
Three deaths occurred after emergency operations, two of which failed to stop the
bleeding, accounting for all of the deaths in the series (3 [19%] of 16). A trend
was noted toward increased death with necrotizing pancreatitis (P =.07) and
emergency surgery (P =.06). Ranson's criteria were not found to be predictive of
death in this series. Surgical drainage procedures were required in seven (44%)
of 16 patients for infections (n = 3) or mass effect of the pseudoaneurysm (n =
3). The mean size of pseudoaneurysms that required operative intervention for
secondary complications was 13.9 cm, compared with 7.7 cm for all others in the
series (P =.046). Long-term follow-up was available in all 13 survivors at a mean
of 44 months (range, 1-108 months). CONCLUSIONS: The management of pancreatic
pseudocyst-associated pseudoaneurysms remains a challenging problem with high
morbidity and death rates. Operation and PAE play complementary management roles.
PAE is recommended as the initial therapy for hemodynamically stable patients.
Surgery should be reserved for actively bleeding, hemodynamically unstable
patients; for failed embolization; and for other secondary complications such as
infection or extrinsic compression.
PMID- 11013037
TI - Suggested treatment protocol for improving patency of femoral-infrapopliteal
cryopreserved saphenous vein allografts.
AB - PURPOSE: Cryopreserved saphenous vein allografts are used for femoral
infrapopliteal bypass graft purposes when adequate autogenous vein is
unavailable. Anticoagulation, immunosuppression therapy, or both have been
suggested means for improving allograft patency. Immunosuppression has
significant cost and morbidity and has produced variable results. Our successful
treatment of luminal surface hypercoagulability associated with certain
endovascular procedures prompted the use of an anticoagulation protocol
prospectively to improve graft patency and limb salvage for patients receiving
femoral-infrapopliteal cryopreserved saphenous vein allografts. METHODS: Between
September 1995 and October 1999, 24 patients (15 men and nine women) were
enrolled in a prospective clinical trial for salvage of 26 severely ischemic
lower limbs with femoral-infrapopliteal cryopreserved saphenous vein allograft
bypass grafts. All patients were treated with a protocol (aspirin, low-dose
heparin, low molecular weight dextran 40, dipyridamole, and warfarin), and no
immunosuppressive agents were used. The cryopreserved saphenous vein allografts
were matched to patients by ABO and Rh compatibility. Indications for
revascularization were ischemic rest pain (n = 8), nonhealing ulcer (n = 13), or
focal gangrene (n = 5), and no usable autogenous vein was available. Follow-up
ranged from 2 to 35 months (mean, 19 months). We studied the location and type of
outflow anastomosis, specific outflow vessel, morbidity, death, secondary
procedures (digital/transmetatarsal amputation), and complications related to the
treatment protocol. Life table analyses of primary graft patency and limb salvage
were compared with other current reported data. RESULTS: Primary graft patency
with Kaplan-Meier life table analysis was 96% at 6 months, 87% at 12 months, and
82% at 18 and 24 months. There were no reoperations for acute graft occlusion.
One graft underwent late segmental aneurysmal degeneration and rupture. There
were no procedure-related deaths or bleeding complications. During late follow
up, anticoagulation was discontinued in three patients (12%) because of
gastrointestinal bleeding. Limb salvage was 88% at 6 months and 80% at 12, 18,
and 24 months. Patients returned to ambulatory status that was limited only by
their other comorbidities. CONCLUSION: Femoral-infrapopliteal bypass graft for
limb salvage with a cryopreserved saphenous vein allograft can be an acceptable
alternative when autogenous vein is not available. Our treatment protocol
substantially improved allograft patency and limb salvage when compared with
current published data.
PMID- 11013038
TI - Incidence and risk factors of late rupture, conversion, and death after
endovascular repair of infrarenal aortic aneurysms: the EUROSTAR experience.
European Collaborators on Stent/graft techniques for aortic aneurysm repair.
AB - OBJECTIVE: The EUROSTAR (European Collaborators on Stent/graft techniques for
aortic aneurysm repair) Registry was established in 1996 to collect data on the
outcome of treatment of patients with infrarenal aortic aneurysms with
endovascular repair. To date, 88 European centers of vascular surgery have
contributed. The purpose of the study was to evaluate the results of this
treatment in the medium term (up to 4 years) according to the analysis of "hard"
or primary end points of rupture, late conversion, and death. PATIENTS AND
METHODS: Patients with aortic aneurysms suitable for endovascular aneurysm repair
were notified to the EUROSTAR Data Registry Centre before treatment to eliminate
bias due to selective reporting. The following information was collected on all
patients: (1) demographic details and the anatomic characteristics of their
aneurysms, (2) details of the endovascular device used, (3) complications
encountered during the procedure and the immediate outcome, (4) results of
contrast enhanced computed tomographic imaging at 3, 6, 12, and 18 months after
operation and at yearly intervals thereafter, and (5) all adverse events. Life
table analysis was performed to determine the cumulative rates of (1) death from
all causes, (2) rupture, and (3) late conversion to open repair. Risk factors for
rupture and late conversion were identified through regression analysis. RESULTS:
By March 2000, 2464 patients had been registered, and their mean duration of
follow-up was 12.19 months (SD, 12.3 months). There were 14 patients with
confirmed rupture of their aneurysms. The cumulative rate (risk) of rupture was
approximately 1% per year. Emergency surgery was undertaken in 12 (86%) patients,
of whom five (41.6%) survived. Two patients who were not treated surgically also
died, which resulted in an overall death rate of 64.5% (9/14) of the patients.
Significant risk factors for rupture were proximal type I endoleak (P =.001),
midgraft (type III) endoleak (P =.001), graft migration (P =.001), and
postoperative kinking of the endograft (P =.001). Forty-one patients underwent
late conversion to open repair with a perioperative mortality rate of 24.4%
(10/41). The cumulative rate (risk) of late conversion was approximately 2.1% per
year. Risk factors (indications) for late conversion were proximal type I
endoleak (P =. 001), midgraft (type III) endoleak (P =.001), type II endoleak (P
=. 003), graft migration (P =.001), graft kinking (P =.001), and distal type I
endoleak (P =.001). CONCLUSIONS: Endovascular repair of infrarenal aortic
aneurysms with the first- and second-generation devices that predominated in this
study was associated with a risk of late failure, according to an analysis of
observed hard end points of 3% per year. Action taken to address the risk factors
identified by the study may improve results in the future.
PMID- 11013039
TI - Reducing the risk of carotid surgery: a 7-year audit of the role of monitoring
and quality control assessment.
AB - BACKGROUND AND PURPOSE: The current risk of stroke after carotid endarterectomy
may be worse than reported in the international trials. Because studies have
suggested that most operative strokes follow surgeon error, the aim of the
current study was to audit the impact of introducing a strategy of perioperative
monitoring and quality control assessment on outcome. METHODS: A total of 500
patients underwent carotid endarterectomy with intraoperative transcranial
Doppler scan monitoring, completion angioscopy, and 3 hours of postoperative
transcranial Doppler scan monitoring. The last of these guided selective dextran
therapy in patients with high rates of postoperative embolization, which in
previous series has been shown to be highly predictive of progression to
thromboembolic stroke. RESULTS: Intimal flaps were repaired in 3% of patients and
luminal thrombus removed in 4% of patients. The rate of intraoperative stroke was
0.2%. A total of 313 patients had more than one embolus detected postoperatively
(96% within 2 hours of flow restoration), but only 22 patients had sustained
embolization requiring dextran. Embolization ceased in all but one patient
receiving dextran, although the dose had to be increased in seven patients (36%).
One patient was unable to receive adequate dextran therapy because of severe
cardiac failure. Overall, the 30-day death/stroke rate was 2.2%, no patient had a
perioperative stroke because of carotid thrombosis, and the rate of ipsilateral
embolic stroke was 0.8%. Most complications resulted from cardiac pathology or
intracranial hemorrhage. CONCLUSIONS: A program of monitoring and quality control
assessment has been associated with a 60% decrease in the operative risk in
comparison with that observed before implementation of the protocol.
PMID- 11013040
TI - Stent placement for treatment of central and peripheral venous obstruction: a
long-term multi-institutional experience.
AB - PURPOSE: The clinical success and patency of central and peripheral venous stents
in patients with symptomatic venous obstruction (SVO) were assessed. METHODS: The
records of patients with SVO treated with venous stents from 1992 to 1999 were
reviewed. Demographic and procedural variables were analyzed to determine their
effect on clinical success, primary patency, and secondary patency. Patency was
determined by means of a follow-up duplex scan or venogram. RESULTS: Forty
central venous (CV) and 14 peripheral venous (PV) obstructions were treated in 49
patients. Sixty-five stents were placed (50 CV and 15 PV), 54 in previously
unstented lesions and 11 in previously stented lesions. Causes of CV lesions
included catheter placement (82%), tumor compression (6%), arteriovenous fistula
(AVF) and no prior catheter (2%), and other (10%). All PV lesions resulted from
complications of dialysis. Indications for CV stents included limb edema (46%),
AVF malfunction (30%), both limb edema and AVF malfunction (14%), and other
(10%). PV stent indications were AVF malfunction (86%) and limb edema (14%).
Thirteen CV stents indicated to treat tumor compression (three cases), May
Thurner syndrome (one case), deep venous thrombosis (three cases), superior vena
cava syndrome (one case), and lower-extremity catheter-related lesions (five
cases) were excluded from the analysis of clinical outcome. Fifty-two stents (37
CV and 15 PV) were included in the analysis of clinical outcome. All CV lesions
included in the analysis were complications of prolonged catheterization. Eighty
nine percent of patients had end-stage renal disease and an AVF. Complications
developed in 26% of patients with PV stents and in no patients with CV stents (P
<.002). The mean follow-up period was 16 months. Sixty-two percent of patients
required a reintervention for recurrent SVO. Only 32% of the interventions
resulted in sustained symptomatic improvement. For CV stents, the primary patency
rate was 85%, 27%, and 9% at 3, 12, and 24 months, respectively; the secondary
patency rate was 91%, 71%, and 39% at 3, 12, and 24 months, respectively; and the
clinical success rate was 94%, 94%, and 79%, at 3, 12, and 24 months,
respectively. For PV stents, the primary patency rate was 73%, 17% and 17% at 3,
12, and 24 months, respectively; the secondary patency rate was 80%, 56%, and 35%
at 3, 12, and 24 months, respectively; and the clinical success rate was 92%,
75%, and 42% at 3, 12 and 24 months, respectively. CONCLUSION: Stents provide a
temporary benefit in most patients with central or peripheral upper-extremity
SVO. Regular follow-up and reinterventions are required to maintain patency and
achieve long-term clinical success. Stents used for CV lesions have higher
clinical success rates than stents used for PV lesions. Patients with a
reasonable life expectancy or who are unable to return for subsequent procedures
should be considered for undergoing alternative therapy.
PMID- 11013041
TI - Percutaneous endovascular repair of infrarenal abdominal aortic aneurysms: a
feasibility study.
AB - BACKGROUND: Endovascular grafting has markedly reduced the invasiveness of the
treatment of abdominal aortic aneurysms. By using a modification of technique for
available closure devices, we have been able to achieve percutaneous repair of
aneurysms. This study reviewed our initial experience with this technique.
METHODS: Demographics and background data from patients undergoing endovascular
repair of abdominal aortic aneurysms were reviewed from prospectively collected
registry data. Operative notes and angiographic and computed tomography scan data
were retrospectively reviewed to assess the success of the percutaneous approach.
RESULTS: Fourteen patients have undergone percutaneous placement of the AneuRx
(Medtronic, Sunnyvale, Calif) endovascular graft, with a modification of the
technique for the Prostar (Perclose, Redwood City, Calif) device for access site
closure. Main graft body introduction with a 22F sheath proved successful in nine
of 12 (75%) deployments. Contralateral limb deployment through a 16F sheath was
successful in 10 of 14 deployments (71.4%). Reasons for conversion to open groin
incisions include inadequate percutaneous hemostasis (six cases), iliofemoral
dissection (four cases), device failure (one case), and compromised distal flow
(one case). Percutaneous deployment success appears to be improved with larger
iliac artery dimensions, decreased calcification, and limited tortuosity, because
of the limitation of complications related to delivering a larger diameter
sheath. Of the 13 percutaneous endograft insertions that were attempted, six
(46.2%) were completely successful. CONCLUSION: Percutaneous deployment of
available devices is technically feasible by using modifications of technique
with percutaneous closure devices, despite large introducer sizes. Further
experience with this technique offers the potential for identifying patients in
whom this will prove successful and for even further reducing hospital stay and
recovery times for aneurysm repair.
PMID- 11013042
TI - Relationship between preoperative patency of the inferior mesenteric artery and
subsequent occurrence of type II endoleak in patients undergoing endovascular
repair of abdominal aortic aneurysms.
AB - OBJECTIVES: The purpose of this study was (1) to find out whether preoperative
inferior mesenteric artery (IMA) patency (on radiographic imaging) predicts IMA
related endoleaks after endovascular repair of infrarenal abdominal aortic
aneurysms, (2) to determine feasibility of measuring aneurysm sac pressures in
patients with endoleaks, and (3) to report early evidence of effective
endovascular obliteration of IMA endoleaks. METHODS: We studied 76 consecutive
cases of infrarenal aortic aneurysms that were repaired with an endovascular
approach (March 1998-April 1999). RESULTS: There were 13 (17%) endoleaks
persistent 30 days after the procedure. Eleven (85%) of these 13 were IMA-related
endoleaks, which were documented with selective superior mesenteric artery
angiography. The preoperative finding (on computed tomographic scan) of a patent
IMA does not always predict an IMA-related endoleak, but results in a
statistically and clinically significant higher ratio of patients with IMA
related endoleaks in the immediate postoperative period (24% versus 3%, P <.035).
In eight of the 11 patients with persistent IMA-related endoleaks, measurement of
intra-aneurysm sac pressures was possible, and six of these patients had systemic
pressures within the excluded aneurysm sac. Nine (82%) of 11 IMA-related
endoleaks were successfully obliterated by means of selective IMA embolization.
CONCLUSIONS: Many endoleaks are caused by a patent IMA, and this can result in
persistence of systemic pressure within the aneurysm sac. The preoperative
finding (on computed tomographic scan) of a patent IMA is a predictor of
increased rates of IMA endoleaks, and IMA endoleaks can be successfully
obliterated through endovascular procedures, after endovascular abdominal aortic
aneurysm repair.
PMID- 11013043
TI - Endothelial cell response to different mechanical forces.
AB - PURPOSE: Endothelial cells (ECs) are subjected to the physical forces induced by
blood flow. The aim of this study was to directly compare the EC signaling
pathway in response to cyclic strain and shear stress in cultured bovine aortic
ECs. MATERIALS AND METHODS: The ECs were seeded on flexible collagen I-coated
silicone membranes to examine the effect of cyclic strain. The membranes were
deformed with a 150-mm Hg vacuum at a rate of 60 cycle/min for up to 120 minutes.
For a comparison of the effect of shear stress, ECs from the same batch as used
in the strain experiments were seeded on collagen I-coated silicone sheets. The
ECs were then subjected to 10 dyne/cm(2) shear with the use of a parallel flow
chamber for up to 120 minutes. Activation of the mitogen- activated protein
kinases was assessed by determining phosphorylation of extracellular signal
regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 with
immunoblotting. RESULTS: ERK, JNK, and p38 were activated by both cyclic strain
and shear stress. Both cyclic strain and shear stress activated JNK with a
similar temporal pattern and magnitude and a peak at 30 minutes. However, shear
stress induced a more robust and rapid activation of ERK and p38, compared with
cyclic strain. CONCLUSIONS: Our results indicate that different mechanical forces
induced differential activation of mitogen-activated protein kinases. This
suggests that there may be different mechanoreceptors in ECs to detect the
different forces or alternative coupling pathways from a single receptor.
PMID- 11013044
TI - Pulsatile wall motion and blood pressure in aneurysms with open and thrombosed
endoleaks--comparison of a wall track system and M-mode ultrasound scanning: an
in vitro and animal study.
AB - OBJECTIVE: Pulsatile wall motion has been suggested as a means by which to
evaluate abdominal aortic aneurysms after exclusion from the circulation to
determine whether the treatment has been effective. The objective of this study
was to investigate the relations between pulsatile wall motion and both the mean
and pulse pressures within the aneurysmal sac for both patent and thrombosed
endoleaks. Furthermore, we compared the measurements of pulsatile wall motion by
means of M-mode ultrasound scanning and a wall track system to determine the most
reliable technique. METHODS: First, interobserver and intraobserver variability
of M-mode ultrasound scan measurements was determined at different pressure
levels in a cow iliac artery placed in an in vitro circulation. M-mode ultrasound
scanning and a wall track system were compared in the same model. Second, in an
animal experiment, an aneurysm and endoleak model with both patent and thrombosed
endoleaks was created. Systemic and aneurysmal mean and pulse pressures were
recorded synchronically with pulsatile wall motion by means of M-mode ultrasound
scanning and a wall track system. RESULTS: The intraobserver and interobserver
variability values for M-mode ultrasound scan measurement in vitro were 0.11 mm
(SD = 0.10 mm) and 0.15 mm (SD = 0.13 mm), respectively. In the animal study, a
significant difference existed with respect to the level of pulse pressure within
the aneurysmal sac between the group with pulsatile wall motion and the group
without such motion (P <.0001). The presence of pulsatile wall motion was not
correlated with the level of aneurysmal mean pressure. The level of pulsatile
wall motion determined by means of M-mode ultrasound scanning correlated well
with the level determined by means of the wall track system (r = 0. 74; P =.01).
For the level of pulsatile wall motion determined by means of M-mode ultrasound
scanning, a significant difference between patent and thrombosed endoleaks
existed (P =.04). For detecting endoleaks, the sensitivity and specificity of
pulsatile wall motion as determined by means of the wall track system were 52%
and 100%, respectively, and the sensitivity and specificity of pulsatile wall
motion as determined by means of M-mode ultrasound scanning were 64% and 67%,
respectively. For the detection of pulse pressure in the aneurysmal sac, the
sensitivity and specificity of pulsatile wall motion as determined by means of
the wall track system were 76% and 100%, respectively, and the sensitivity and
specificity of pulsatile wall motion as determined by means of M-mode ultrasound
scanning were 90% and 71%, respectively. CONCLUSIONS: We found that pulsatile
wall motion is correlated with aneurysmal pulse pressure but not with the mean
level of pressure inside the aneurysm. Although measurements of pulsatile wall
motion are of great theoretic value when groups of patients who have undergone
endovascular aneurysm repair are being compared, this method appears to be
unreliable in a clinical setting with respect to determining whether the
aneurysmal sac is still pressurized in individual patients.
PMID- 11013045
TI - Recombinant thrombomodulin inhibits arterial smooth muscle cell proliferation
induced by thrombin.
AB - PURPOSE: Restenosis after angioplasty or bypass grafting to restore circulation
to ischemic organs is still an unsolved problem. Thrombin generated in high
concentrations at the sites of vascular injury plays a central role in thrombosis
and hemostasis. alpha-Thrombin has also been implicated as a mitogen for smooth
muscle cell (SMC) proliferation that contributes to arterial restenosis.
Thrombomodulin has a high affinity of binding with thrombin and converts thrombin
from a procoagulant to an anticoagulant. This study was designed to examine
whether thrombomodulin could also moderate the thrombin-mediated SMC
proliferative response. METHODS: Porcine carotid artery SMCs (passages 4-7) were
plated onto 96-well plates and incubated for 3 days. After growth arrest in a
defined serum-free medium for 2 to 3 days, SMCs were subjected to the reagents as
follows: (1) human alpha-thrombin, (2) recombinant human soluble thrombomodulin
containing a chondroitin sulfate moiety, (3) thrombin receptor agonist peptide
(SFLLRNPNDKYEPF), and (4) alpha-thrombin or thrombin receptor agonist peptide
combined with recombinant thrombomodulin (rTM). The viability and proliferation
status of SMCs were quantified with MTT (thiazolyl blue) mitochondrial function
and bromodeoxyuridine (BrdU)-DNA incorporation assays. RESULTS: Human alpha
thrombin increased SMC proliferation in a dose dependent manner by more than 25%
and 30% with thrombin 1 U/mL to 3 U/mL compared with control groups on day 7 (P
<.006). rTM concentrations from 0.5 microg/mL to 3 microg/mL have no significant
effect on SMC growth. The stimulation of SMC proliferation induced by alpha
thrombin at 0.5 U/mL, 1 U/mL, and 2 U/mL was significantly inhibited with rTM at
2 microg/mL and 3 microg/mL on days 3, 7, and 10 as evaluated with MTT assay (P
<.01 to <.05) and BrdU-DNA incorporation assay on day 3 (P <.008). Thrombin
receptor agonist peptide increased SMC BrdU-DNA incorporation at 48 hours (P
<.007), and its effect was not altered by rTM. CONCLUSION: rTM containing all of
the extracellular domains of thrombomodulin inhibits the effect of thrombin on
SMC proliferation in vitro. Because thrombin is a mitogenic mediator of SMC in
vascular injury, inhibition of its function in vivo could help to prevent SMC
hyperplasia. The success of further studies in vivo may lead to use of rTM for
decreasing or preventing arterial restenosis.
PMID- 11013047
TI - Bypass graft to the contralateral internal jugular vein for venous outflow
obstruction of a functioning hemodialysis access fistula.
AB - As survival among patients with renal failure improves, vascular access becomes
more difficult, and preservation of functioning access increases in importance.
Subclavian vein thrombosis associated with a distal arteriovenous fistula can
result in massive and debilitating swelling of the affected extremity. We
describe a novel crossover bypass grafting procedure to the contralateral
internal jugular vein in a patient with a thrombosed internal jugular and
subclavian vein. This procedure resulted in preservation of the functioning
arteriovenous fistula and resolution of the symptoms. Unlike previously described
crossover procedures to the contralateral basilic or axillary veins, this bypass
graft has the added benefit of not obviating future fistula creation in that
extremity.
PMID- 11013046
TI - Laparoscopic release of celiac artery compression syndrome facilitated by
laparoscopic ultrasound scanning to confirm restoration of flow.
AB - A 43-year-old woman presented with symptomatic mesenteric ischemia caused by
median arcuate ligament compression of her celiac artery. Magnetic resonance
angiography clearly demonstrated stenosis of the proximal celiac artery. She
underwent laparoscopic decompression by division of the ligament and excision of
the celiac plexus. Laparoscopic Doppler ultrasound scanning demonstrated markedly
improved flow in the artery. She was discharged in 15 hours and reported complete
resolution of her symptoms at the 3-month postoperative visit. Laparoscopy
provides a less invasive but equally effective method for decompressing the
celiac artery as well as assessing adequacy of flow after its release.
PMID- 11013048
TI - Malignant carotid body tumor: a case report.
AB - Carotid body tumors (CBTs) have an unpredictable history with no correlation
between histology and clinical behavior. Of reported cases since 1891, local and
distant metastases appear in approximately 10% of cases and remain the hallmark
of malignancy. Currently, there are not enough data to support a single treatment
regimen for malignant CBTs. The reported case demonstrates some unanswered issues
with regard to malignant CBTs to include lymph node dissection, the need for
carotid resection, and the role of radiation therapy. A 46-year-old pathologist
underwent a resection of a Shamblin I CBT, to include jugular lymph node
sampling, without complication. There was lymph node involvement, and tumor cells
were found on the margins of the pathologic specimen. Subsequent carotid
resection with reversed interposition saphenous vein graft and modified neck
dissection were performed again without complication. Follow-up at 4 years has
been uneventful. Diagnosis of CBTs with the use of magnetic resonance
angiography, magnetic resonance imaging, color flow duplex scanning, and the role
of arteriography are reviewed. The current treatment options are discussed with
reference to primary lymph node sampling, carotid resection, and neck dissection
in malignant cases. This case demonstrates that the unpredictable nature of CBTs
and their malignant potential warrant aggressive initial local treatment to
include jugular lymph node sampling and complete tumor resection.
PMID- 11013050
TI - The distinguished service award for the Society for Vascular Surgery, 2000: D.
Emerick Szilagyi, MD.
PMID- 11013049
TI - Ruptured internal carotid aneurysm resulting from neurofibromatosis: treatment
with intraluminal stent graft.
AB - PURPOSE: This report shows a method of treatment for life-threatening hemorrhage
due to rupture of an aneurysm in the cervical internal carotid artery caused by
neurofibromatosis. METHODS: Ten days after delivery of healthy twins, a 28-year
old woman with known neurofibromatosis had sudden massive swelling in the left
neck. After initial tracheostomy, angiography confirmed rupture of the mid
cervical internal carotid artery as well as contribution to the resultant
pseudoaneurysm from external carotid branches. Treatment began with coil
embolization of the external carotid branches. The internal carotid lesion, a
defect approximately 1 cm in length, was then closed through use of two stent
grafts, each made from Palmaz stents and 3-mm polytetrafluorethylene grafts
predilated to 6 mm. The neck hematoma was then evacuated surgically. RESULTS:
Completion angiography and computed tomographic scanning confirmed control of the
hemorrhage. The patient survived neurologically intact with the exception of
cranial nerve deficits caused by the hemorrhage. The tracheostomy tube was
removed 3 weeks postoperatively. Follow-up computed tomographic scanning showed a
gradual decrease in the size of the cervical soft tissue and no recurrent
aneurysm. CONCLUSION: Neurofibromatosis is a rare cause of aneurysmal
degeneration of blood vessels. Repair of a ruptured cervical internal carotid
artery aneurysm, though feasible, is difficult with stent grafts; however, this
is a better option than surgical intervention in inaccessible vessels.
PMID- 11013051
TI - Neuromusculoskeletal conditions of the upper extremity: are they due to
repetitive occupational trauma?
AB - The significance of neuromusculoskeletal conditions in the workplace is the
subject of much discussion among occupational medicine professionals. There are
differing philosophies as to what constitutes appropriate diagnostic criteria for
identification of these conditions. The traditional diagnostic model requires the
presence of objective pathology. An emerging symptom-based model accepts that
symptoms by themselves can constitute a diagnostic entity. The extent to which
these conditions are considered to be associated with occupational activity
depends greatly upon which of the two models is employed. This chapter presents
an overview of each diagnostic model and a discussion of the impact each has on
the prevalence of identified conditions and the manner in which the various
diagnostic requirements can affect treatment, prevention, and disability rating
protocols.
PMID- 11013052
TI - S.P.I.C.E.--a model for reducing the incidence and costs of occupationally
entitled claims.
AB - A review of national statistics and recent studies strongly suggests that current
administrative and medical systems, when applied to managing workers'
compensation claims and other disability-related benefit programs, are often
ineffective and costly, and can even promote disability. With numerous medical
and occupational health articles published daily, it is difficult to develop
practical strategies for daily management of disability claims that make use of
current information. It is the authors' view that a comprehensive, dynamic model
for management exists within the military's "Forward Treatment" methodology. This
model, originally published in The Journal of Occupational Rehabilitation, has
been expanded to include those methods demonstrated in literature to both reduce
claims and deal with them in an efficient, fair, and timely manner. Because
military personnel and employed individuals are similarly entitled, the
military's proven model can be effective in reducing claim rates and costs
associated with workers' compensation as well as short- and long-term disability
programs. The model, given the acronym S.P. I.C.E., includes five components:
Simplicity, Proximity, Immediacy, Centrality, and Expectancy.
PMID- 11013053
TI - Unified fitness report for the workplace.
AB - Fitness statements often are required of physicians by patients, employers,
governmental agencies, and insurance providers to determine if the patient is fit
for duty. Physicians making these ability statements are legally obligated to
carefully justify them when placing or excluding individuals from the workplace.
The Americans with Disabilities Act (ADA) mandates that medical providers use
justifiable criteria and rational thought when determining the capability and
risk of an individual. This chapter reviews the legal requirements of the ADA for
employers and physicians and presents a uniform methodology that both can use to
determine the performance capability of an individual with a temporary or
permanent impairment or disability.
PMID- 11013054
TI - The importance of illness behavior in disability management.
AB - Abnormal illness behaviors, ranging from non-deliberate distortion to intentional
deception, are associated with clinical phenomena that lie along a continuum from
unconscious symptom exaggeration to psychiatric disorders and malingering.
Failure to recognize abnormal illness behavior leads to inappropriate treatment
and erroneous estimates of impairment or disability. This review is divided into
three sections. First, basic terms are defined, including dissimulation,
distortion, deception, misattribution, false imputation, and malingering. Second,
syndromes characterized by abnormal illness behavior are described, including
somatization, somatoform disorders, factitious disorders, and symptom
magnification. Third, methods for detecting deception are illustrated, including
maximum voluntary effort assessment, objective personality inventories, and
symptom validity testing.
PMID- 11013055
TI - Management of chronic pain and control of long-term disability.
AB - Chronic pain has become a major public health problem. Often, the availability of
entitlement programs as well as psychosocial, occupational, and other nonmedical
factors-rather than objective pathophysiology-are major contributors to
disability. In this chapter, the authors discuss the relationship between
impairment and disability and detail factors likely to predict or contribute to
adverse clinical outcome and disability. Guidelines for disability prevention
also are examined.
PMID- 11013056
TI - Assessment and management of upper and lower extremity impairment and disability.
AB - The assessment and management of occupational and nonoccupational injuries and
illnesses of the extremities require knowledge of the same concepts of impairment
and disability that are used when evaluating or treating problems of other body
systems. Dr. Talmage discusses the need for an accurate and objectively
verifiable diagnosis and focuses on upper extremity pain in workers and the term
tendinitis'. The concept of maximal medical improvement is considered, with
examples of knee injuries to the menisci and localized articular cartilage
defects. Causation controversies are explored using carpal tunnel syndrome as the
example. The impairment rating process is illustrated by use of the AMA Guides
system. A "checklist" to insure completeness of the examination of extremity
problems is offered. Disability assessment and management is discussed, with an
emphasis on the difference between abilities (capacities) and risk-based
restrictions. The author concludes with thoughts on how to minimize disability.
PMID- 11013057
TI - Worksite disability management model for effective return-to-work planning.
AB - The growth of disability management programs represents a paradigm shift from
traditional clinic-based rehabilitation services to worksite-based interventions
that dramatically reduce lost time and costs. Supportive policies and steps in
the return-to-work process are illustrated, from the point of worker injury and
early intervention, through work ability assessment, return-to-work planning, job
site accommodation, and successful return to work. Creative return-to-work
options, including "job banks," are discussed as practical methods to facilitate
the worker's gradual return to full duty status while completing the medical
recovery process. Worker, worksite, and community resource factors related to
return-to-work outcomes are discussed.
PMID- 11013059
TI - Use of functional employment testing to facilitate safe job placement.
AB - Functional testing has evolved to a new sophistication, and is currently used in
a variety of situations to assist the employer and physician in safely placing an
individual at the job site. The functional capacity evaluation can be employed in
several ways, not only to place individuals safely in jobs, but also to monitor
their progress throughout recovery from an injury or illness and aid in the
establishment of vocational counseling and planning. Many legal issues now alter
employer techniques for hiring and assigning people to jobs. This state of
affairs places increasing importance on functional testing.
PMID- 11013058
TI - Psychosocial factors and risk of pain and disability.
AB - This article reviews the research on the risk of pain and disability due to
psychosocial variables. Variables such as general distress, psychopathology,
depression, abuse, and catastrophizing are discussed in relation to the risk of
disability. Ways to conceptualize the complex relationships among pain,
disability, and several psychosocial variables are also explored. In addition,
the identification of adaptive and of protective ways to manage pain and decrease
the risk of disability is highlighted. Finally, the authors recommend areas for
future research.
PMID- 11013060
TI - To smile again. Reanimation for unilateral facial palsy.
PMID- 11013061
TI - Organ donation. 3. Brain stem death.
AB - Following an exploration of nurses' perceptions of organ donation, and of consent
and patient's rights in the preceding articles, this series concludes with an
examination of brain stem death, and in particular the literature which
challenges popular assumptions about it. This makes challenging and sometimes
disturbing reading, but as the author reminds us, these are issues which theatre
nurses cannot ignore.
PMID- 11013062
TI - Lifeskills training. You've read the books ... now it's time to apply it to life!
PMID- 11013063
TI - Horizontal violence in the operating room.
PMID- 11013064
TI - Concepts of health and the health promoting role of the perioperative nurse.
AB - Health promotion is an important part of the work of a wide range of healthcare
professionals. The United Kingdom Central Council (UKCC 1983) states that
education is a statutory responsibility and one of the most important and
challenging aspects of the nurse's role. The nurse has a professional as well as
a moral responsibility to educate for health as well as to care for the sick
(UKCC 1994).
PMID- 11013065
TI - A framework for perioperative advanced practice.
PMID- 11013066
TI - Breathing circuits and their uses.
PMID- 11013067
TI - Estrogen-induced remodeling of hypothalamic neural circuitry.
AB - For decades, sexual behavior has been a valuable model system for behavioral
neuroscientists studying the neural basis of motivated behaviors. One striking
example of a change in motivation is the binary switch in sexual receptivity that
occurs during the estrous cycle in female rats. Investigations of the neural
basis of this change in behavior have fundamentally advanced our understanding of
both behaviorally relevant neural pathways and basic mechanisms of steroid action
in the brain. These advances have made this behavioral model system a staple of
neuroendocrinology. A challenge that remains before us, given our current
understanding of the circuitry and chemistry, is to develop a coherent model of
how neural plasticity in the hypothalamus contributes to the dependence of this
behavior on motivational state. This review will focus on the ventromedial
nucleus of the hypothalamus, especially its ventrolateral subdivision. First, the
anatomical, neurochemical, and functional aspects of the macro- and
microcircuitry of this brain region will be discussed, followed by a discussion
of the likely mechanisms of estrogen action within the ventrolateral VMH. Then,
the evidence for estrogen-induced neural plasticity will be considered, including
a comparison with the effects of estrogen on synaptic organization in other brain
regions. Finally, a working model of neural plasticity within the ventrolateral
VMH microcircuitry will be presented as a starting point for future experiments
to verify or, more likely, revise and expand.
PMID- 11013068
TI - Growth hormone in the brain: characteristics of specific brain targets for the
hormone and their functional significance.
AB - During the past decade studies have shown that growth hormone (GH) may exert
profound effects on the central nervous system (CNS). For instance, GH
replacement therapy was found to improve the psychological capabilities in adult
GH deficient (GHD) patients. Furthermore, beneficial effects of the hormone on
certain functions, including memory, mental alertness, motivation, and working
capacity, have been reported. Likewise, GH treatment of GHD children has been
observed to produce significant improvement in many behavioral problems seen in
these individuals. Studies also indicated that GH therapy affects the
cerebrospinal fluid levels of various hormones and neurotransmitters. Further
support that the CNS is a target for GH emerges from observations indicating that
the hormone may cross the blood-brain barrier (BBB) and from studies confirming
the presence of GH receptors in the brain. It was previously shown that specific
binding sites for GH are present in discrete areas in the CNS of both humans and
rats. Among these regions are the choroid plexus, hippocampus, hypothalamus, and
spinal cord. The density of GH binding in the various brain regions was found to
decline with increasing age. More recently, we were able to clone and determine
the structure of several GH receptors in the rat and human brain. Although the
brain receptor proteins for the hormone were shown to differ in molecular size
compared to those present in peripheral tissues the corresponding transcripts did
not seem to differ from their peripheral congeners. GH receptors in the
hypothalamus are likely to be involved in the regulatory mechanism for hormone
secretion and those located in the choroid plexus have been suggested to have a
role in the receptor-mediated transport of GH across the BBB. The functions
mediated by the GH receptors identified in the hippocampus are not yet known but
recently it was speculated that they may be involved in the hormone's action on
memory and cognitive functions.
PMID- 11013069
TI - New members of the parathyroid hormone/parathyroid hormone receptor family: the
parathyroid hormone 2 receptor and tuberoinfundibular peptide of 39 residues.
AB - The parathyroid hormone (PTH) family currently includes three peptides and three
receptors. PTH regulates calcium homeostasis through bone and kidney PTH1
receptors. PTH-related peptide, probably also through PTH1 receptors, regulates
skeletal, pancreatic, epidermal, and mammary gland differentiation and bladder
and vascular smooth muscle relaxation and has a CNS role that is under
investigation. Tuberoinfundibular peptide of 39 residues (TIP39) was recently
purified from bovine hypothalamus based on selective PTH2 receptor activation.
PTH2 receptor expression is greatest in the CNS, where it is concentrated in
limbic, hypothalamic, and sensory areas, especially hypothalamic periventricular
neurons, nerve terminals in the median eminence, superficial layers of the spinal
cord dorsal horn, and the caudal part of the sensory trigeminal nucleus. It is
also present in a number of endocrine cells. Thus TIP39 and PTH2 receptor
influenced functions may range from pituitary and pancreatic hormone release to
pain perception. A third PTH-recognizing receptor has been found in zebrafish.
PMID- 11013070
TI - Fine-scale comparative mapping of the human 7q11.23 region and the orthologous
region on mouse chromosome 5G: the low-copy repeats that flank the Williams
Beuren syndrome deletion arose at breakpoint sites of an evolutionary
inversion(s).
AB - Williams-Beuren syndrome (WBS) is a developmental disorder caused by
haploinsufficiency for genes deleted in chromosome band 7q11.23. A common
deletion including at least 16-17 genes has been defined in the great majority of
patients. We have completed a physical and transcription map of the WBS region
based on analysis of high-throughput genome sequence data and assembly of a
BAC/PAC/YAC contig, including the characterization of large blocks of gene
containing low-copy-number repeat elements that flank the commonly deleted
interval. The WBS deletions arise as a consequence of unequal crossing over
between these highly homologous sequences, which confer susceptibility to local
chromosome rearrangements. We have also completed a clone contig, genetic, and
long-range restriction map of the mouse homologous region, including the
orthologues of all identified genes in the human map. The order of the
intradeletion genes appears to be conserved in mouse, and no low-copy-number
repeats are found in the region. However, the deletion region is inverted
relative to the human map, exactly at the flanking regions. Thus, we have
identified an evolutionary inversion with chromosomal breakpoints at the sites
where the human 7q11.23 low-copy-number repeats are located. Additional
comparative mapping suggests a model for human chromosome 7 evolution due to
serial inversions leading to genomic duplications. This high-resolution mouse map
provides the framework required for the generation of mouse models for WBS
mimicking the human molecular defect.
PMID- 11013071
TI - Human-chimpanzee DNA sequence variation in the four major genes of the renin
angiotensin system.
AB - The renin angiotensin system (RAS) is involved in blood pressure control and
water/sodium metabolism. The genes encoding the proteins of this system are
candidate genes for essential hypertension. The RAS involves four main molecules:
angiotensinogen, renin, angiotensin I-converting enzyme, and the angiotensin II
type 1 receptor (encoded by the genes AGT, REN, DCP1, and AGTR1, respectively).
We performed a molecular screening over 17,037 bp of the coding and 5' and 3'
untranslated regions of these genes, from three to six common chimpanzees. We
identified 44 single-nucleotide polymorphisms (SNPs) in chimpanzee samples,
including 18 coding-region SNPs, 5 of which led to an amino acid replacement. We
observed common and different features at various sites (synonymous,
nonsynonymous, and noncoding) within and between the four chimpanzee genes: (1)
the nucleotide diversity at noncoding sites was similar; (2) the nucleotide
diversity at nonsynonymous sites was low, probably reflecting purifying
selection, except for the AGT gene; (3) the nucleotide diversity at synonymous
sites, which was dependent on the G+C content at the third position of the codon,
was high, except for the AGTR1 gene. Comparison of the chimpanzee SNPs with those
previously reported for humans identified 119 sites with fixed differences
(including 62 coding sites, 17 of which resulted in amino acid differences
between the species). Analysis of polymorphism within species and divergence
between species shed light on the evolutionary constraints on these genes. In
particular, comparison of the pattern of mutation at polymorphic and fixed sites
between humans and chimpanzees suggested that the high G+C content of the DCP1
gene was maintained by positive selection at its silent sites. Finally, we
propose 68 ancestral alleles for the human RAS genes and discuss the implications
for their use in future hypertension-susceptibility association studies.
PMID- 11013072
TI - Cross-referencing radiation hybrid data to the recombination map: lessons from
mouse chromosome 18.
AB - We are building a framework map of known-order anchor markers between the mouse
T31 radiation hybrid (RH) panel and the recombination map based on The Jackson
Laboratory (TJL) interspecific backcross panels using the established genetic
order to evaluate and strengthen the RH results. In making this map comparison,
we have elucidated several problems inherent in RH mapping and minimized these by
careful attention to data gathering and interpretation methods. We describe
lessons and pitfalls of developing radiation hybrid maps, using the example of
mouse Chromosome 18, for which we have built a framework map of microsatellite
anchor loci spanning the entire chromosome at significant LOD with no gaps. Sixty
five D18Mit- simple sequence length polymorphism (SSLP) markers form a continuous
linkage along the T31 RH Chromosome 18 (RH map length 1598 cR, genetic length 41
cM) with all LODs greater than 6. These markers are also placed on TJL
interspecific backcrosses, and the order of the markers in the two systems is in
complete agreement. We are continuing to cross-reference the RH data to TJL
backcross data for the other mouse chromosomes to improve further the power of RH
mapping and to integrate more precisely the extensive existing recombination
mapping data for the mouse with the incoming radiation hybrid map data.
PMID- 11013073
TI - The characterization of the common fragile site FRA16D and its involvement in
multiple myeloma translocations.
AB - Fragile sites appear as breaks, gaps, or decondensations on metaphase chromosomes
when cells are grown under specific culture conditions. The breaks are nonrandom,
appearing in defined, conserved locations throughout the mammalian genome. Common
fragile sites, as their name implies, are present in virtually all individuals.
With three common fragile sites cloned, their mechanism of expression and the
role, if any, they play in human disease are still unclear. We have assembled a
BAC contig of >1 Mb across the second most active common fragile site, FRA16D
(16q23.2). We fluorescently labeled these BACs and used them as probes on
metaphases from aphidicolin-induced lymphocytes and demonstrated that FRA16D
decondensation/breakage occurs over a region of at least 1 Mb. Thus, this is the
largest common fragile site cloned to date. Microsatellite markers that map
within FRA16D show a very high loss in prostate, breast, and ovarian tumors,
indicating that loss within this fragile site may be important in the development
or progression of these tumors. In addition, a common t(14q32;16q23)
translocation is observed in up to 25% of all multiple myelomas (MM). We
localized four of four such cloned t(14;16) MM breakpoints within the FRA16D
region. This work further demonstrates that the common fragile sites may play an
important role in cancer development.
PMID- 11013074
TI - Quantitative trait loci affecting prion incubation time in mice.
AB - Although the gene encoding prion protein (PrP) is the major determinant of
susceptibility to prion disease, other genes also affect prion incubation time in
mice and may be involved in prion replication. Scrapie incubation time was
analyzed as a quantitative trait using crosses between SJL/J and CAST/Ei mice;
these mouse strains encode identical PrP molecules but have different incubation
periods. Our analysis revealed loci on Chromosomes 9 and 11 that affect prion
susceptibility.
PMID- 11013075
TI - Identification and structural analysis of human RBM8A and RBM8B: two highly
conserved RNA-binding motif proteins that interact with OVCA1, a candidate tumor
suppressor.
AB - The OVCA1 gene is a candidate for the breast and ovarian tumor suppressor gene at
chromosome 17p13.3. To help determine the function(s) of OVCA1, we used a yeast
two-hybrid screening approach to identify OVCA1-associating proteins. One such
protein, which we initially referred to as BOV-1 (binder of OVCA1-1) is 173 or
174 amino acids in length and appears to be a new member of a highly conserved
RNA-binding motif (RBM) protein family that is highly conserved evolutionarily.
Northern blot analysis revealed that BOV-1 is ubiquitously expressed and that
three distinct messenger RNA species are expressed, 1-, 3.2-, and 5.8-kb
transcripts. The 1-kb transcript is the most abundant and is expressed at high
levels in the testis, heart, placenta, spleen, thymus, and lymphocytes. Using
fluorescence in situ hybridization and the 5.8-kb complementary DNA probe, we
determined that BOV-1 maps to both chromosome 5q13-q14 and chromosome 14q22-q23.
Further sequence analysis determined that the gene coding the 1- and the 3.2-kb
transcripts (HGMW-approved gene symbol RBM8A) maps to 14q22-q23, whereas a second
highly related gene coding for the 5.8-kb transcript resides at chromosome 5q13
q14 (HGMW-approved gene symbol RBM8B). The predicted proteins encoded by RBM8A
and RBM8B are identical except that RBM8B is 16 amino acids shorter at its N
terminus. Molecular modeling of the RNA-binding domain of RBM8A and RBM8B, based
on homology to the sex-lethal protein of Drosophila, identifies conserved
residues in the RBM8 protein family that are likely to contact RNA in a protein
RNA complex. The conservation of sequence and structure through such an
evolutionarily divergent group of organisms suggests an important function for
the RBM8 family of proteins.
PMID- 11013077
TI - Identification and characterization of the miniature pig Huntington's disease
gene homolog: evidence for conservation and polymorphism in the CAG triplet
repeat.
AB - Huntington's disease (HD) is associated with a significant expansion of a CAG
trinucleotide repeat, which results in a lengthened polyglutamine tract in the
single gene product, huntingtin, on human 4p16.3. We isolated cDNA clones that
encompassed the entire coding sequence of the miniature pig HD gene (Sus HD) from
two porcine testis cDNA libraries. The cDNA contig revealed a 12,749-nucleotide
transcript coding for a 345-kDa protein (3139 amino acid residues), which
exhibited 96% peptide sequence homology to human huntingtin. Northern blot
analysis revealed that the Sus HD gene was ubiquitously expressed as two large
transcripts of approximately 11 and 13 kb in size in all the tested tissues, much
like the human HD gene. The CAG trinucleotide repeat was found to be interrupted
by CAA triplets and to encode 17 or 18 consecutive glutamine residues. In our
laboratory stock of miniature pig, three allotypes in the triplet repeat sequence
were found. Thus, the Sus HD gene closely resembles its human counterpart in
terms of sequence and expression pattern. In particular, human-miniature pig
similarities in the normal length of the CAG triplet repeat as well as its repeat
number polymorphism may indicate that miniature pig would provide a good animal
model for Huntington's disease.
PMID- 11013076
TI - Identification of the human Mnk2 gene (MKNK2) through protein interaction with
estrogen receptor beta.
AB - We have identified and characterized the human Mnk2 gene (HGMW-approved gene
symbol MKNK2) through a yeast two-hybrid screen in which the Mnk2 protein
interacted with the ligand-binding domain of estrogen receptor beta (ERbeta).
Human Mnk2 is homologous to murine Mnk2 ( approximately 94% identical) and human
Mnk1 (71% identical), both of which encode MAP kinase interacting kinases that
are phosphorylated and activated by ERK1 and 2. This report presents a thorough
genomic sequence analysis revealing that the human Mnk2 gene has two C-terminal
splice variants, designated here as Mnk2a and Mnk2b. These two isoforms are
identical over the first 385 amino acids of the coding sequence and differ only
in the final exon which encodes an additional 80 residues for Mnk2a and 29
residues for Mnk2b. A more detailed biological analysis in yeast showed that the
Mnk2 interaction was selective for ERbeta as opposed to ERalpha and that the
interaction was specific to Mnk2b as opposed to Mnk2a or Mnk1. This pattern was
reproduced in a mammalian two-hybrid system using a completely different set of
fusion partners; and in both yeast and mammalian systems, the addition of
estradiol decreased the interaction. While it remains unknown whether ERbeta is a
substrate of Mnk2, the interaction of these two proteins is reminiscent of
ERalpha and ribosomal S6 kinase (p90-RSK), another MAP kinase-regulated kinase
homologous to Mnk2 that is known to phosphorylate ERalpha.
PMID- 11013078
TI - Characterization of mRAD18Sc, a mouse homolog of the yeast postreplication repair
gene RAD18.
AB - The RAD18 gene of the yeast Saccharomyces cerevisiae encodes a protein with ssDNA
binding activity that interacts with the ubiquitin-conjugating enzyme RAD6 and
plays an important role in postreplication repair. We identified and
characterized the putative mouse homolog of RAD18, designated mRAD18Sc. The
mRAD18Sc open reading frame encodes a 509-amino-acid polypeptide that is strongly
conserved in size and sequence between yeast and mammals, with specific
conservation of the RING-zinc-finger and the classic zinc-finger domain. The
degree of sequence conservation between mRAD18Sc, RAD18, and homologous sequences
identified in other species (NuvA from Aspergillus nidulans and Uvs-2 from
Neurospora crassa) is entirely consistent with the evolutionary relationship of
these organisms, strongly arguing that these genes are one another's homologs.
Consistent with the presence of a nuclear translocation signal in the amino acid
sequence, we observed the nuclear localization of GFP-tagged mRAD18Sc after
stable transfection to HeLa cells. mRNA expression of mRAD18Sc in the mouse was
observed in thymus, spleen, brain, and ovary, but was most pronounced in testis,
with the highest level of expression in pachytene-stage primary spermatocytes,
suggesting that mRAD18Sc plays a role in meiosis of spermatogenesis. Finally, we
mapped the mRAD18Sc gene on mouse chromosome 6F.
PMID- 11013079
TI - Annexin A11 (ANXA11) gene structure as the progenitor of paralogous annexins and
source of orthologous cDNA isoforms.
AB - The genomic organization of the annexin A11 gene was determined in mouse and
human to assess its congruity with other family members and to examine the
species variation in alternative splicing patterns. Mouse annexin A11 genomic
clones were characterized by restriction analysis, Southern blotting, and DNA
sequencing, and the homologous human gene (HGMW-approved gene symbol ANXA11) was
deciphered from high-throughput genomic sequence with coanalysis of expressed
sequence tags. Exons 6-15 of the tetrad core repeat region differ from annexins
A7 and A13 but are spliced identically to other phylogenetic descendents, making
annexin A11 the putative primary progenitor of up to nine paralogous human
annexins. The 5' regions consist of untranslated exon 1, followed by an extensive
intron 1 comprising almost half the total gene length of >40 kb, and additional
GC-rich exons 2-5 encoding the proline- and glycine-rich amino-terminus. Distinct
cDNA isoforms in cow and human were determined to be unique to each species and
hence of dubious general significance for this gene's function. Multiple
transcription start sites were revealed by primer extension analysis of the mouse
gene, and transfection constructs containing the prospective promoter generated
transcriptional activity comparable to that of the SV40 promoter. Internal
repetitive elements and vicinal gene markers were mapped for the complete human
annexin A11 gene sequence to characterize the surrounding genomic environment.
PMID- 11013080
TI - Cloning of the genomic locus of mouse SH2 containing inositol 5-phosphatase
(SHIP) and a novel 110-kDa splice isoform, SHIPdelta.
AB - The SH2 domain containing inositol 5'-phosphatase (SHIP) was initially described
as a 145-kDa protein phosphorylated on tyrosines upon growth factor and cytokine
stimulation. It was shown to be phosphorylated after Fc and B cell receptor
activation and plays a role in negative signaling. Different isoforms of the SHIP
protein result from alternative mRNA splicing, proteolysis, or a combination of
both. The expression of discrete SHIP isoforms changes with the potential
developmental-dependent maturation state of myeloid cells, suggesting mechanisms
for the regulation of SHIP interactions with other signaling molecules. A p135
(SHIPbeta) spliced isoform is known to be expressed in developing myeloid cells.
Now we have identified a new SHIP isoform, SHIPdelta, which is the product of an
out-of-frame splice with a deletion of 167 nucleotides in the C-terminal region,
resulting in an approximately 110-kDa protein. Biochemically, SHIPdelta differs
from SHIPalpha by exhibiting little or no tyrosine phosphorylation or association
with the signaling protein Shc after M-CSF activation of FD-Fms cells. In
addition, we have characterized the structure of the entire SHIP genomic locus,
which provides a basis for understanding the alternative splicing events. SHIP is
expressed in hematopoiesis and spermatogenesis, and we also describe the promoter
for the SHIP gene, which has potential for explaining the tissue-specific
expression pattern.
PMID- 11013081
TI - Human NB-2 of the contactin subgroup molecules: chromosomal localization of the
gene (CNTN5) and distinct expression pattern from other subgroup members.
AB - NB-2 is one of the neural recognition molecules in the contactin subgroup, which
belongs to the immunoglobulin superfamily. In rat, the six molecules in this
subgroup that have been reported to date are contactin, TAG-1, BIG-1, BIG-2, NB
2, and NB-3. We have isolated cDNAs encoding the two splicing isoforms of human
NB-2. The long isoform of human NB-2 consists of 1100 amino acids residues that
are 91% homologous to rat NB-2 at the amino acid sequence level. The short
isoform lacks 74 amino acid residues between residues 19 and 93 of the long
isoform. Among various regions of the adult human brain, high-level expression of
NB-2 was detected in the amygdala and occipital lobe, whereas expression was low
in the corpus callosum, caudate nucleus, and spinal cord. Although there were
some differences, the expression pattern of NB-2 was the most similar to that of
BIG-1 in the brain. Likewise, contactin and BIG-2 exhibited similar expression
patterns. The expression of TAG-1 showed the least regional differences. The
human NB-2 gene (CNTN5) was mapped to chromosome 11q21-q22.2 by fluorescence in
situ hybridization. Our results suggest that the NB-2 gene may contribute to
human neurological disorders.
PMID- 11013083
TI - Dating the origin of the V170M mutation causing non-type I cystinuria in Libyan
Jews by linkage disequilibrium and physical mapping of the SLC7A9 gene.
AB - Cystinuria is an autosomal recessive disorder of the transepithelial transport of
amino acids, clinically manifested by the development of kidney stones. Mutations
in the gene encoding rBAT (SLC3A1, on chromosome 2p16.3) are linked to type I
cystinuria, while the SLC7A9 locus (19q13.1), expressing b0,+ AT protein, is
involved in non-type I cystinuria, which is very common among Libyan Jews.
Applying two methods for linkage disequilibrium analysis to haplotype data
spanning six 19q12-q13.1 polymorphic markers, and relying on the physical
distances between the markers and the recently mapped SLC7A9 (CSNU3) locus, the
age of the founder missense V170M mutation causing non-type I cystinuria in Jews
of Libyan ancestry is calculated to be approximately 14 to 15 generations (g)
(95% confidence interval: 9-20 g) or slightly more. The estimated age dates the
most recent common ancestor of the mutation-bearing chromosomes back to the time
(or some decades before) Jewish families settled in Libya following their
expulsion from the Iberian Peninsula. This finding makes the molecular population
genetics of cystinuria understandable in the context of the Libyan Jews' history.
PMID- 11013084
TI - Genetic and physical mapping of the cerebellar deficient folia (cdf) locus on
mouse chromosome 6.
AB - Cerebellar deficient folia (cdf) is a recessive mouse mutation causing ataxia and
cerebellar cytoarchitectural abnormalities, including hypoplasia, foliation
defects, and Purkinje cell ectopia. To identify the cdf gene, we have generated a
high-resolution genetic map of a 3.24 +/- 0.55 cM (95% CI) region encompassing
the cdf gene using 1997 F2 mice generated from a (C3H/HeSnJ-cdf/cdf x CAST/Ei)F1
intercross. Linkage analysis showed that the cdf gene cosegregates with D6Mit208,
D6Mit359, and D6Mit225. A contig of five YACs, nine BACs, and three P1s was
constructed across the cdf nonrecombinant region. Based on genetic and physical
maps, the cdf gene was localized to the 0.28 +/- 0.23 cM (95% CI) interval
between D6Mit209 and D6Ack1. These results will greatly facilitate the map-based
cloning of the cdf gene, which in turn should further knowledge of the molecular
mechanisms of neuronal positioning and foliation during cerebellar development.
PMID- 11013082
TI - Functional characterization of the gene encoding RLIM, the corepressor of LIM
homeodomain factors.
AB - RLIM is a RING H2 zinc finger protein that acts as a negative coregulator for LIM
homeodomain transcription factors. We have isolated genomic lambda clones that
cover the entire mouse RLIM-encoding Rnf12 gene. The Rnf12 gene encompasses 20 kb
and consists of at least five exons and four introns. Several transcriptional
start sites within a 24-bp region were mapped around 300 nt upstream of the
translational start site. Rnf12-specific mRNA can be detected in many tissues as
revealed by Northern blot analysis. Transient cotransfections reveal that the
proximal Rnf12 promoter can be activated in vitro by ubiquitously and more
restrictively expressed transcription factors, some of which are known mediators
of signal transduction pathways, e.g., mammalian Kruppel-like transcription
factors, Sox and ets-related proteins, and RBP-J. We isolated a cDNA encoding
human RLIM, which is highly conserved with mouse and chick RLIM. By fluorescence
in situ hybridization and interspecific backcross analysis, we have localized the
Rnf12 gene to the central regions of mouse and human chromosome X.
PMID- 11013085
TI - BAC contig from a 3-cM region of mouse chromosome 11 surrounding Brca1.
AB - Even with the completion of a draft version of the human genome sequence only a
fraction of the genes identified from this sequence have known functions.
Chromosomal engineering in mouse cells, in concert with gene replacement assays
to prove the functional significance of a given genomic region or gene,
represents a rapid and productive means for understanding the role of a given set
of genes. Both techniques rely heavily on detailed maps of chromosomal regions,
initially to understand the scope of the regions being modified and finally to
provide the cloned resources necessary to allow both finished sequencing and
large insert complementation. This report describes the creation of a BAC clone
contig on mouse chromosome 11 in a region showing conservation of synteny with
sequences on human chromosome 17. We have created a detailed map of an
approximately 3-cM region containing at least 33 genes through the use of
multiple BAC mapping strategies, including chromosome walking and multiplex
oligonucleotide hybridization and gap filling. The region described is one of the
targets of a large effort to create a series of mice with regional deletions on
mouse chromosome 11 (33-80 cM) that can subsequently be subjected to further
mutagenesis.
PMID- 11013086
TI - Molecular cloning of ring finger protein 21 (RNF21)/interferon-responsive finger
protein (ifp1), which possesses two RING-B box-coiled coil domains in tandem.
AB - We have cloned the full length of a novel cDNA, named ring finger protein 21
(RNF21), composed of the RING finger-B box-coiled coil (RBCC) domain and the
B30.2 domain, which are characteristic of the RBCC-B30.2 family. As a structural
feature, the RNF21 cDNA possessed at least three kinds of isoforms, due to
alternative splicing, consisting of the long form with the RBCC-RBCC-B30.2
domain, the medium form with the RBCC-B30.2 domain, and the short form with only
the RBCC domain. Moreover, respective transcripts corresponding to the three
isoforms were detected in various human organs by reverse transcription-PCR and
Northern blot analyses. Interestingly, the medium form of the RNF21 mRNA
expressed most predominantly was dramatically up-regulated within 8-16 h by
interferon stimulation of HeLa cells. These findings suggest that RNF21 is a
downstream gene that may mediate interferon's biological action.
PMID- 11013087
TI - Curative treatment of cerebral arteriovenous malformations by embolisation using
cellulose acetate polymer followed by surgical resection.
AB - AIM: To investigate the usefulness of embolising cerebral arteriovenous
malformations (AVMs) with a cellulose acetate polymer solution before surgical
resection. METHODS: The cases of 12 patients with AVMs treated by embolisation
before surgical resection were renewed. Two types of cellulose acetate polymer
solutions were used to occlude 40 feeding vessels. All patients underwent
surgical resection 1-51 days after embolisation. RESULTS: Reduction of the nidus
volume after embolisation ranged from 20% to nearly 100%. Transient neurological
deficits occurred in three patients, persistent deficits occurred in one and
there were no haemorrhagic complications. All but one arteriovenous malformation
were completely resected. Embolisation helped to identify feeding vessels and
ease dissection. Histopathological examination of resected specimens disclosed
mild inflammatory reactions in the acute stage and no unfavourable granulomatous
changes in the chronic stage. CONCLUSION: Embolisation with cellulose acetate
polymer solutions followed by surgical resection is safe and efficacious for
treating cerebral AVMs.
PMID- 11013088
TI - Seizure control after radiosurgery on cerebral arteriovenous malformations.
AB - Among 462 cases of cerebral arteriovenous malformation (AVM) treated with gamma
radiosurgery, the initial presentations were haemorrhage in 68%, epilepsy in
12.8%, neurological deficits in 3.2%, minor symptoms in 7.6% and asymptomatic in
4.5% respectively. There were 79 cases (17.1%) who had had a convulsive seizure
before radiosurgery and they were classified into two groups: 58 cases presented
with seizure as an initial symptoms (group A) and the other 21 cases mostly had
seizures following intracranial haemorrhage (group B). Before radiosurgery,
generalised seizure was the predominant seizure pattern in both groups, followed
by pure partial and complex partial seizures. There was no major difference in
seizure patterns or seizure frequency in group A and B. At radiosurgery AVMs were
treated with a mean maximum dose of 37.2 Gy and a marginal dose of 19.8 Gy.
Seizures had apparently decreased in most of the cases at the last follow-up
(mean 24 months) according to the obliteration of the nidus. Seizures were either
decreased or had disappeared in 91.6% of group A and 62.5% of group B patients.
The overall results indicate that seizures improved in 85.5%, were changed in
11.6% and deteriorated in 2.9% of patients. Radiosurgery is effective not only
for the obliteration of nidus of cerebral AVM, but also for seizure control, even
before complete occlusion of the nidus.
PMID- 11013089
TI - Image-guided microsurgery with the Mehrkoordinaten Manipulator system for
cerebral arteriovenous malformations.
AB - Four patients with cerebral arteriovenous malformations (AVMs) underwent image
guided microsurgery with the Mehrkoordinaten Manipulator (MKM) system, which
integrates a robotic microscope with a computer workstation. The patients were
all male, from 8 to 51 years old (mean = 24), all presenting with intracerebral
haemorrhage. The lesion was located in the deep sylvian fissure in one patient,
the fronto-parieto-occipital area in one and the trigone in two. Stereotactic
computed tomography and magnetic resource imaging of 1-mm slices were taken. The
extent of AVM and the draining vein, predetermined with the MKM workstation,
could be superimposed on the microscopic view, resulting in minimum scalp
incision and craniotomy, as well as allowing for a stereotactic approach to deep
seated lesions. Superimposition of the contour of the lesion was also useful for
resecting the lesion, although intraoperative diagnosis of the total resection
required intraoperative digital subtraction angiography. In conclusion, image
guided microsurgery with the MKM system can assist minimally invasive and
maximally effective microsurgery for cerebral AVMs.
PMID- 11013090
TI - Endovascular treatment of aneurysms associated with cerebral arteriovenous
malformations: experiences after the introduction of Guglielmi detachable coils.
AB - The authors have treated 172 patients with arteriovenous malformation (AVM) since
1993. Among them, 25 patients had aneurysms with a total number of 43. The
aneurysms were divided into four groups; proper feeder aneurysm (4), flow-related
distal aneurysm (beyond the circle of Willis or M1, 7), flow-related proximal
aneurysm (26) and remote aneurysm (6). Guglielmi detachable coil (GDC)
embolisation was performed in 12 patients with 15 aneurysms. Gamma knife
radiosurgery for AVM was performed in 10 of those 12 patients. Two of the proper
feeder aneurysms were embolised with liquid material, together with the
corresponding part of the AVM. The other aneurysms were treated surgically (14)
or observed (12). There was no bleeding from aneurysms after treatment. In
conclusion, GDC embolisation is a useful treatment for aneurysms associated with
AVM, especially if the AVM is treated by radiosurgery. Liquid embolisation of a
proper feeder aneurysm is one of the treatment options. Ltd.
PMID- 11013091
TI - Surgery or gamma -knife for the treatment of arteriovenous malformations?
AB - Decision making for either surgery or gamma-knife for the treatment of
arteriovenous malformations (AVMs) cannot be uniform. The skill of the
neurosurgeon in operating on AVMs is now being compared with that of the gamma
knife. The decision varies from case to case and is to be taken by the
neurosurgeon. This report presents three cases in which such decision making was
not easy. Case 1 was a non-ruptured cingulate AVM of 2.5 cm diameter in the
cingulate cortex. The operative field was anticipated to be very narrow between
the parietal bridging veins. Case 2 was a tiny ruptured AVM in the speech-motor
area which was buried underneath the cortex. Case 3 was a large ruptured thalamo
stiriate-capsular AVM with feeders from the anterior and posterior choroidal
arteries. All cases were operated without serious morbidity. A combination of pre
operative intravascular surgery (cases 1 and 3) or postoperative gamma-knife
(case 3) was adopted. In conclusion, there is no unitary rule to decide on
surgery or gamma-knife for the treatment of AVMs. It depends on what good or harm
the responsible surgeon or the gamma-knife does.
PMID- 11013092
TI - Treatment of arteriovenous malformation of the brain--preliminary experience.
AB - With the availability of new techniques, such as intravascular embolisation and
radiosurgery, the therapeutic approach to arteriovenous malformations (AVMs) of
the brain has recently been modified. The present study reports the authors,
experiences in treating AVMs over the past 13 years. Spetzler-Martin grading of
AVMs was I and II in 19 cases, III in 12, IV in 5 and V in 1 case. Four
therapeutic regimens were utilised: surgical resection alone, embolisation and
resection, and radiosurgery alone or after surgical resection. Generally, for low
grade AVMs (Spetzler-Martin grades I, II and III), the therapeutic choice was
surgical resection in 27 cases, in combination with pre-operative embolisation in
two of these patients. Two cases received radiotherapy only and one case received
radiosurgery after embolisation, while one case was treated conservatively. Of
the five cases of grade IV, four required surgical treatment, whereas the fifth
case was treated conservatively. Favourable results (good recovery and moderate
disability) were obtained in 96% of the low-grade AVMs as compared with the high
grade AVMs (66%) that had a poor outcome (due to primary brain damage resulting
from haemorrhage at the onset in three cases and due to postoperative re-bleeding
in one case). This report summarises preliminary experience in treating
intracranial AVMs by surgical resection, intravascular embolisation and
radiotherapy. Good therapeutic results can be expected by combining these
therapeutic modalities.
PMID- 11013093
TI - Successful surgical treatment of a large mixed pial-dural arteriovenous
malformation.
AB - A large mixed pial-dural arteriovenous malformation was successfully treated by
surgical resection and occlusion of the draining veins. Treatment of this type of
malformation is discussed.
PMID- 11013094
TI - Surgical management of cerebral arteriovenous malformations with intraoperative
digital subtraction angiography.
AB - Complete excision of cerebral arteriovenous malformations (AVMs) is requisite to
improving the outcome of patients with AVMs. Five patients with a small or medium
cerebral AVM underwent surgery with an intraoperative digital subtraction
angiography (DSA) unit. There were no residual AVMs and no complications in the
examination of intraoperative DSA. The findings of postoperative angiography were
consistent with those of intraoperative DSA. Intraoperative DSA provided the
benefits of not only identification of a feeding artery, but also recognition of
the complete excision during surgery.
PMID- 11013095
TI - Dural arteriovenous malformations associated with cerebral aneurysms.
AB - Only limited information is available concerning dural arteriovenous
malformations (AVMs) found in association with cerebral aneurysms. The present
report focuses on six such cases, concentrating attention on clinical
characteristics and significance. Of a total of 46 dural AVMs encountered over a
given period, six (13%) were linked with cerebral aneurysms. Particularly strong
associations were noted for dural AVMs in the anterior cranial fossa (three of
four cases) and convexity (all of three cases). With dural AVMs in the anterior
cranial fossa, subarachnoid haemorrhage is common, so that where this is
encountered the possibility of a complicating aneurysm should be considered in
order to select an appropriate treatment.
PMID- 11013096
TI - Haemodynamic evaluation of cerebral arteriovenous malformations by quantification
of transit time using high speed digital subtraction angiography: basic
considerations.
AB - It is important to evaluate the haemodynamics of cerebral arteriovenous
malformations (AVMs) in order to predict and avoid complications following
surgical intervention. This study measured the transit time of each component of
AVMs by high-speed digital subtraction angiography (DSA) to understand the
haemodynamics and to evaluate which parameter is an appropriate indicator for the
monitoring. Eleven cases of cerebral AVMs were studied. Haemodynamics were
evaluated by analysis of tracer transit using DSA. Tracer transit parameters
including transit time and peak time were calculated by application of gamma
fitting to time density curve, and measured in the following compartments;
feeding artery, nidus and draining vein. Significant correlations of tracer
transit parameters were present among compartments. Although there was no
significant correlation of nidus volume and tracer transit parameters, the peak
time was shorter in haemorrhage cases than in non-haemorrhage cases. Measurements
of tracer transit parameters by high-speed DSA may be a useful tool for
characterising and monitoring the haemodynamics of AVMs following surgical
intervention.
PMID- 11013097
TI - Colour Doppler flow imaging of the superior ophthalmic vein in dural
arteriovenous fistulas before and after surgery.
AB - The aim of this study was to examine the clinical significance of the colour
Doppler flow imaging (CDFI) findings of the superior ophthalmic vein (SOV) in
intracranial dural arteriovenous fistulas (DAVF). The SOV was examined by CDFI in
12 cases of DAVF before and after surgery. Before surgery, the average SOV
diameter was 3.57+/-1.18 mm (mean +/- standard deviation, which was significantly
wide (P<0.05) compared with the control value. One case showed reversed flow.
Four cases showed an abnormal waveform. The cases with the more severe clinical
symptoms showed wider SOV diameters and more abnormal waveforms than those with
mild clinical symptoms. Postoperatively, the mean SOV diameter and mean
resistance index improved significantly (P< 0.05); the flow direction and
waveform became normal in each. The SOV CDFI findings were found to be useful as
screening and follow-up techniques for the intracranial DAVFs.
PMID- 11013098
TI - Surgery for dural arteriovenous fistula in superior sagittal sinus and transverse
sigmoid sinus.
AB - The aim of this study was to evaluate the outcome of surgically treated dural
arteriovenous fistula (DAVF). The authors performed surgical removal of DAVF in
12 patients. The locations of DAVF were the transverse sigmoid sinus in seven
patients and superior sagittal sinus in five patients. These 12 patients had
undergone endovascular embolisation prior to removal. Among them, six patients
were completely cured, according to angiography immediately after embolisation,
but these six patients showed the recurrence of DAVF within 1 year. The other six
patients showed a decrease of feeding vessels. Therefore, all 12 patients
underwent surgical removal of DAVF. The surgical strategies were as follows. The
feeding vessels and the cortical veins with retrograde filling were occluded and
cut. The affected sinus was skeletonised, and if it was occluded or almost
occluded, the sinus was removed. Postoperatively, transient aphasia was seen in
one patient. There was no surgical morbidity or mortality. During the follow-up
period (mean 2.9 years), no recurrence of DAVF was seen. Surgical treatment is a
safe and effective treatment manoeuvre for DAVF around the transverse sigmoid
sinus and superior sagittal sinus.
PMID- 11013099
TI - Spinal intradural perimedullary arteriovenous fistula with varix in infant.
AB - A rare occurrence of type IV spinal arteriovenous malformation (intradural
perimedullary arteriovenous fistula) is described in an 18-month-old boy
initially misdiagnosed with Guillain-Barre syndrome. An intramedullary mixed
intensity mass lesion at Th1 was demonstrated by magnetic resonance imaging
together with flow voids over the dorsal aspect of the swollen spinal cord.
Angiography demonstrated an intradural perimedullary arteriovenous fistula
including an intraparenchymal vascular pocket. After partial embolisation of the
posterior spinal arteries through the left intercostal-radicular artery, the
arteriovenous fistula was removed completely together with an organised
haematoma. The fistula directly opened into a vascular pocket, which was
confirmed pathologically to be a varix. The postoperative course was uneventful,
and the patient resumed ambulation within 4 months. The case, subclassifiable as
a type IVb spinal perimedullary AVF, was unique given its location and the
patient's age at presentation.
PMID- 11013100
TI - Combination of intraoperative embolisation with surgical resection for treatment
of giant cerebral arteriovenous malformations.
AB - OBJECTIVE: To reduce the risk of surgical resection of giant arteriovenous
malformation (AVM) and prevent normal perfusion pressure breakthrough (NPPB) and
thus to lower postoperative mortality. METHODS: During the operation, which was
carried out under general anaesthesia, the proximal ends of the feeding arteries
were first ligated and 0.5 ml IBCA mixed with 0.5 ml of 5% glucose was injected
into the vessels towards the AVM, then the malformed vessels were totally
resected. Postoperative digital subtraction angiography (DSA) of the four vessels
was performed in all patients. RESULTS: Fifty patients with giant AVMs survived
after operation, only 6 (12.0%) had transient neurological dysfunction and 44
(88.0%) recovered after a follow-up of 6-36 months. No patient suffered from
NPPB. CONCLUSIONS: The embolisation could block the arteriovenous shunts
sufficiently to decrease the blood flow away from the normal areas of the brain
so as to prevent the incidence of intra- and post-operative rebleeding,
especially in NPPB. Therefore, the combination of intraoperative embolisation
with surgical resection is an effective strategy in the treatment of giant
cerebral AVMs, which makes it possible to operate on patients who used to be
regarded as inoperable cases.
PMID- 11013101
TI - Strategy for the treatment of arteriovenous malformations.
AB - The treatment of arteriovenous malformations (AVMs) is still a challenging
problem in the neurosurgical field. The deep-seated AVMs are a definite
indication for radiosurgery for the small AVMs and with pre-embolisation for the
large AVMs. The superficial AVMs are a good indication for surgery. In the case
of small AVMs, surgery alone is a viable option; however, in the case of large
AVMs, pre-operative embolisation is essential for prevention of NPPB (normal
perfusion pressure breakthrough). Embolisation alone cannot be used, except for a
small AVM in the non-eloquent cortex. Preoperative embolisation makes surgery
easy; however, it causes the surrounding cortex to infarct. Hyperperfusion may
occur after the direct removal of high-flow large AVMs, therefore postoperative
management will be difficult in these cases. In eloquent cortex minimally
invasive surgery is more reliable with respect to the morbidity produced.
Therefore in cases of small AVMs in the functional cortex, direct surgery is the
only choice. In cases of high-flow large AVMs, surgery and postoperative
management are risky because of NPPB. Therefore pre-operative embolisation
followed by surgery is a better choice. In high-flow AVMs, local blood
circulation is not decreased by temporary clipping of the feeding arteries. So we
recommend temporary clipping of all feeding arteries, even away from the nidus
where it is easier to control bleeding.
PMID- 11013102
TI - Palliatively treated cerebral arteriovenous malformations: follow-up results.
AB - The purpose of this study was to evaluate the benefits of palliative embolisation
of patients with inoperable intracranial AVMs. It involved the analysis of the
long-term clinical follow-up results of 27 patients with inoperable intracranial
AVMs. Sixteen patients were treated medically and 11 patients received partial
embolisation. The mean size of the lesions was 7.2 +/- 2.6 cm, and the mean
follow-up period was 99 +/- 44 months (range 52-192 months). There were no
significant statistical differences in the sex, age, size, venous drainage
pattern, location of the lesions or presented symptoms. The analysis of the long
term clinical follow-up results showed no significant difference in either the
risk of haemorrhage or clinical status of the patients in the two treatment
groups. Of the 16 patients in the medical treatment group, 8 (50%) showed a
clinical improvement, 3 no improvement and 5 (31%) deterioration. Of the 11
patients in the embolisation group, 5 (45.5%) showed clinical improvement, 3 no
improvement and 3 (27.3%) deterioration (P = 0.871). Twenty-five percent (4
cases) of patients in the medical group and 45.5% (5 cases) of patients in the
embolisation group suffered from haemorrhage during the follow-up period (P =
0.270). Complications related to embolisation occurred in three cases. This
comparative study shows that palliative partial embolisation of intracranial
AVMs, in all probability does not produce better clinical results than medical
treatment.
PMID- 11013103
TI - Haemorrhagic complication after total extirpation of huge arteriovenous
malformations.
AB - Two cases with huge arteriovenous malformations (AVMs) who developed haemorrhagic
complications after surgery are described. The cause of the postoperative
haemorrhage was considered to be the normal perfusion pressure breakthrough
phenomenon and/or occlusive hyperaemia. These two haemodynamic insults possibly
occur simultaneously and induce life-threatening haemorrhage. It was concluded
that a huge high-flow AVM with a large venous ampulla in its deep drainers has a
high risk of a postoperative intravenous thrombosis, resulting in haemorrhage
together with normal perfusion pressure breakthrough phenomenon.
PMID- 11013104
TI - Resectability of Spetzler-Martin grade IV and V cerebral arteriovenous
malformations.
AB - This study retrospectively analysed treatment modalities and outcomes in 63 cases
of high grade cerebral arteriovenous malformations (Spetzler-Martin's
classification grade IV 51, V 12) who were admitted to this institute between
January 1986 and April 1998. Twenty-seven of 37 cases with haemorrhagic onset
received surgical resection with or without pre-operative embolisation. Total
extirpation was achieved in 23 cases, and small residual nidus was treated by
postoperative radiosurgery in two of four subtotally resected cases. Another 6 of
37 haemorrhagic cases received radiosurgery with or without preradiosurgical
embolisation. Four cases with haemorrhagic onset received partial embolisation.
Finally, 29 of 37 haemorrhagic cases obtained complete disappearance of nidus. On
the other hand, 4 of 26 non-haemorrhagic cases received surgical total resection,
5 radiosurgery, 9 partial embolisation and 8 observation without treatment.
Microsurgical morbidity was 9% and mortality was 0%. Post-treatment haemorrhage
was seen in 11 cases (1 after subtotal resection, 4 after radiosurgery, 6 after
partial embolisation) and was fatal in 3 cases. Surgical resection can be
achieved with acceptable morbidity, and complete obliteration of nidus should be
accomplished in any treatment modality to avoid post-treatment haemorrhage.
PMID- 11013105
TI - Embolisation of cerebral arteriovenous malformations to assure successful
subsequent radiosurgery.
AB - This study investigated the angiographic changes in embolised arteriovenous
malformations (AVMs) pre- and post-embolisation and preradiosurgery to clarify
the usefulness of embolisation as a pretreatment for radiosurgery and the
strategy of embolisation for the radiosurgical success. A total of 37 patients
with cerebral AVMs treated over a period of 4 years was investigated. All the
AVMs were embolised with N-butyl cyanoacrylate and 2 months later they were
treated by radiosurgery. The size of AVM nidus reduced just following the
embolisation (mean 21.9 ml to 3.9 ml). The angiogram taken in preparation for
radiosurgery showed a further size reduction in the nidus of 16 AVMs, no change
in 10 and regrowth in 11. In all the cases where size was reduced, the nidus was
densely packed, while all the regrown AVMs were of the diffuse type. Five AVMs
disappeared following radiosurgery, all of which were size-reduction or no-change
cases. In conclusion, to achieve success in subsequent radiosurgery, nidus
embolisation and the occlusion of fistulous and meningeal feeders are mandatory.
Imprudent proximal feeder occlusion and the use of embolic materials with a risk
of recanalisation should be avoided to prevent regrowth of the nidus, which may
lead to errors in planning the radiosurgery to follow.
PMID- 11013106
TI - Strategic embolisation for successful resection of a large cerebral arteriovenous
malformation.
AB - The risks accompanied by the treatment of cerebral arteriovenous malformation
(AVM) are still cumulative despite recent progress in available treatment
options. Pre-operative embolisation is one such option, however, it seldom makes
the surgical resection difficult. The excessive embolised nidus makes the
surgical resection difficult because it cannot be compressed during the resection
surgery and embolised nidus as a 'glue ball' with marginal hypervascular
territory is most difficult to remove. The aim of pre-operative embolisation for
successful surgical resection is to put glue into the marginal part of the nidus
so as to make a cleavage between the surrounding normal tissues. Remaining
feedings via the dilatated leptomeningeal anastomoses from surrounding normal
cortical arteries do not interfere with the resection and can be eliminated
easily by coagulating the pia matter around the nidus. Strategic planning with
regard to the systemic course of treatment, including the manner of resection, is
important for effective pre-operative embolisation.
PMID- 11013107
TI - Surgical resection of cerebral arteriovenous malformation combined with pre
operative embolisation.
AB - To assess the importance of pre-operative embolisation, 27 cases of cerebral
artriovenous malformation (AVM) treated in this institute between July 1994 and
October 1998 were analysed. The patients' ages ranged from 3 to 70 years (average
36.9) with a follow-up period of 1-41 months (average 19.2). The patient
presented with haemorrhage in 21 cases and seizure in five. In 21 of 27 cases,
surgical resection of a nidus was performed, gamma knife therapy was applied in
three and conservative therapy was chosen in three. Of 21 cases treated
surgically, total removal was achieved in 19 cases and a residual nidus was seen
in one (a large basal ganglia AVM). In the remaining case, postoperative
angiography was not available. Pre-operative embolisation followed by surgical
resection of the nidus was performed in seven cases in which there was a large
AVM. A volume index was calculated to indicate the size of the nidus using X x Y
x Z, where X is the maximum diameter (cm) of the nidus on the lateral angiogram,
Y is the diameter (cm) perpendicular to X and Z is the maximum diameter (cm) on
the anteroposter or angiogram. The index averaged 45.9 for the cases in which pre
operative embolisation was performed, while it was 5.6 in the cases without
embolisation. Pre-operative embolisation was performed to reduce the nidus flow
as much as possible, to prevent overload to the surrounding structures. At
surgery, the nidus was resected from the surrounding tissue and care was taken
not to enter the nidus. Postoperatively, the systolic blood pressure was
maintained at 90-100 mmHg for several days in the intensive care unit. The
results were excellent in 15 cases, good in three (hemiparesis due to the initial
haemorrhage remained in all three), fair in one (a patient with a severe
subarachnoid haemorrhage). Two patients died (acute pulmonary oedema and severe
meningitis). Minor postoperative bleeding or oozing was seen in three cases. In
conclusion, reducing the shunt flow through a nidus in a step-wise fashion with
pre-operative embolisation of a large AVM seems to be quite helpful in preventing
postoperative haemodynamic overload to the surrounding brain. It is also
important not to enter the nidus when it is removed at surgery. This helps to
prevent intraoperative and/or postoperative bleeding, and led to successful total
removal of the nidus with a good postoperative course.
PMID- 11013108
TI - Defective deletion mutant amplification.
AB - Defective deletion mutants can be replicated in superinfected cells by parasitism
of the intact virus' replication machinery, and through replication with the host
cell. We show by analysis of a mathematical model that dynamic stability of
superinfected cell growth is crucial in determining the frequency of deletion
mutant infected cells, i.e. there is a critical infectivity threshold
rho(sc)below which the density of proliferative virus is significantly reduced by
the presence of defective deletion mutants. Above rho(sc), proliferative virus
principally occurs as superinfected cells (wild type with defective deletion
mutant). The threshold rho(sc), and the interference effects of the deletion
mutant, increase with deletion mutant parasitism of the wild-type replication
machinery in superinfected cells. The interaction of virally infected cells with
host homeostasis determines whether immune escape by deletion mutant infected
cells is necessary for the interference window to exist. Only when the deletion
mutant has a detrimental effect on infected host cell replication did we observe
periodic behaviour.
PMID- 11013109
TI - On the dynamic persistence of cooperation: how lower individual fitness induces
higher survivability.
AB - We study a model in which cooperation and defection coexist in a dynamical steady
state. In our model, subpopulations of cooperators and defectors inhabit sites on
a lattice. The interactions among the individuals at a site, in the form of a
prisoner's dilemma (PD) game, determine their fitnesses. The chosen PD payoff
allows cooperators, but not defectors, to maintain a homogeneous population.
Individuals mutate between types and migrate to neighboring sites with low
probabilities. We consider both density-dependent and density-independent
versions of the model. The persistence of cooperation in this model can be
explained in terms of the life cycle of a population at a site. This life cycle
starts when one cooperator establishes a population. Then defectors invade and
eventually take over, resulting finally in the death of the population. During
this life cycle, single cooperators migrate to empty neighboring sites to found
new cooperator populations. The system can reach a steady state where cooperation
prevails if the global "birth" rate of populations is equal to their global
"death" rate. The dynamic persistence of cooperation ranges over a large section
of the model's parameter space. We compare these dynamics to those from other
models for the persistence of altruism and to predator-prey models.
PMID- 11013110
TI - Sperm competition games: a comparison of loaded raffle models and their
biological implications.
AB - Our main aim is to compare the additive model, due to Mesterton-Gibbons, and the
multiplicative model, due to Parker, of sperm allocation under sperm competition,
when other influences are treated in the same way. We first review these (and
other) models and their foundations, leading to a generalization of the
multiplicative model. Sperm is assumed to cost energy, and this constraint is
incorporated differently in the two models. These give the same results in the
random-roles situation when the males occupy roles (of first and second to mate)
randomly: the number of sperm ejaculated in the favoured role is greater than
that in the disfavoured role by an amount that depends on the effect of sperm
limitation (i.e. the probability that there is insufficient sperm to ensure full
fertility). If the latter is negligible, or the fertilization raffle fair, this
difference is zero, as Parker found originally. In the constant roles situation
(where males of a particular type always occupy the same role) the predictions
differ: the additive model has the same predictions as in the random roles case,
but the multiplicative model predicts that males of the type occupying the
favoured role ejaculate less than males of the type occupying the disfavoured
role, in accord with Parker's original conclusion. The fitnesses of the two types
of male can be calculated in the multiplicative model: the fitness of the
favoured male is usually higher, even if he has to expend more energy in
"finding" a female, e.g. through fighting, etc. These conclusions relate to inter
male behaviour (i.e. of different male types), as distinct from intra-male
behaviour (i.e. of a given male when in different roles). We analyse situations
in which one male type has some probability of acting in its less usual role:
calculations with varying amounts of sperm limitation are presented. It is found
that the presence of a male of a different type has an effect on intra-male
ejaculate behaviour, which also depends critically on the role usually occupied.
We conclude that the multiplicative model is the more accurate model and provides
more information. Some experimental data on sperm numbers are used to find the
effects of sperm limitation. For species which conform to the loaded raffle
model, sperm limitation typically has small or negligible effects: in this case,
we argue that empiricists should look for equal ejaculates in the two roles when
studying random role situations; when roles are occupied non-randomly average
sperm expenditure should be greater by male types typically occupying the
disfavoured role, but within a male type, expenditure should be greater in the
role it typically occupies.
PMID- 11013111
TI - A mathematical model describing kinetics of conversion of violaxanthin to
zeaxanthin via intermediate antheraxanthin by the xanthophyll cycle enzyme
violaxanthin de-epoxidase.
AB - The xanthophyll cycle is one of the mechanisms protecting the photosynthetic
apparatus against the light energy excess. Its action is still not well
understood on the molecular level. Our model makes it possible to follow
independently the kinetics of the two de-epoxidation steps occurring in the
xanthophyll cycle: the conversion of violaxanthin into antheraxanthin and the
conversion of antheraxanthin into zeaxanthin. Using a simple form of the
transition rates of these two conversions, we model the time evolution of the
concentration pattern of violaxanthin, antheraxanthin and zeaxanthin during the
de-epoxidation process. The model has been applied to describe the reactions of
de-epoxidation in a system of liposome membranes composed of phosphatidylcholine
and monogalactosyldiacylglycerol. Results obtained within the model fit very well
with the experimental data. Values of the transition probabilities of the
violaxanthin conversion into antheraxanthin and the antheraxanthin conversion
into zeaxanthin calculated by means of the model indicate that the first stage of
the de-epoxidation process is much slower than the second one.
PMID- 11013112
TI - Coupled biological oscillators in a cave insect.
AB - Insects that live in the interior of caves show the basic internal temporal
organization of coupled oscillators. An analysis is made of the coupled moulting
and oviposition cycles of Folsomia candida, a cave-dwelling Collembolan, with
regard to their oscillatory nature, their phase dependent responses to external
perturbations, the effect of coupling on these responses, and conjecture about
the link of these cycles with circadian clocks in other organisms.
PMID- 11013113
TI - Optimization of coding potentials using positional dependence of nucleotide
frequencies.
AB - We study the coding potential of human DNA sequences, using the positional
asymmetry function (D(p)) and the positional information function (I(q)). Both
D(p)and I(q)are based on the positional dependence of single nucleotide
frequencies. We investigate the accuracy of D(p)and I(q)in distinguishing coding
and non-coding DNA as a function of the parameters p and q, respectively, and
explore at which parameters p(opt)and q(opt)both D(p)and I(q)distinguish coding
and non-coding DNA most accurately. We compare our findings with classically used
parameter values and find that optimized coding potentials yield comparable
accuracies as classical frame-independent coding potentials trained on prior
data. We find that p(opt)and q(opt)vary only slightly with the sequence length.
PMID- 11013114
TI - Cytokine-modulated regulation of helper T cell populations.
AB - Helper T (Th) cells are a crucial component of the adaptive immune system and are
of fundamental importance in orchestrating the appropriate response to pathogenic
challenge. They fall into two broad categories defined by the cytokines each
produces. Th1 cells produce interferon- gamma and are required for effective
immunity to intracellular bacteria, viruses and protozoa whereas Th2 produce IL-4
and are required for optimal antibody production to T-dependent antigens. A great
deal of experimental data on the regulation of Th1 and Th2 differentiation have
been obtained but many essential features of this complex system are still not
understood. Here we present a mathematical model of Th1/Th2 differentiation and
cross regulation. We model Fas-mediated activation-induced cell death (AICD) as
this process has been identified as an important mechanism for limiting clonal
expansion and resolving T cell responses. We conclude that Th2 susceptibility to
AICD is important for stabilizing the two polarized arms of the T helper
response, and that cell-cell killing, not suicide, is the dominant mechanism for
Fas-mediated death of Th1 effectors. We find that the combination of the anti
proliferative effect of the cytokine TGF- beta and the inhibiting influence of IL
10 on T cell activation are crucial controls for Th2 populations. We see that the
strengths of the activation signals for each T helper cell subset, which are
dependent on the antigen dose, co-stimulatory signals and the cytokine
environment, critically determine the dominant helper subset. Switches from Th1-
to Th2-dominance may be important in chronic infection and we show that this
phenomenon can arise from differential AICD susceptibility of T helper subsets,
and asymmetries in the nature of the cross-suppressive cytokine interactions. Our
model suggests that in some senses a predominantly type 2 reaction may well be
the "default" pathway for an antigen-specific immune response, due to these
asymmetries.
PMID- 11013115
TI - Microvillar ion channels: cytoskeletal modulation of ion fluxes.
AB - The recently presented theory of microvillar Ca(2+)signaling [Lange, K. (1999) J.
Cell. Physiol.180, 19-35], combined with Manning's theory of "condensed
counterions" in linear polyelectrolytes [Manning, G. S. (1969). J. Chem. Phys.51,
924-931] and the finding of cable-like ion conductance in actin filaments [Lin,
E. C. & Cantiello, H. F. (1993). Biophys. J.65, 1371-1378], allows a systematic
interpretation of the role of the actin cytoskeleton in ion channel regulation.
Ion conduction through actin filament bundles of microvilli exhibits unique
nonlinear transmission properties some of which closely resemble that of
electronic semiconductors: (1) bundles of microfilaments display significant
resistance to cation conduction and (2) this resistance is decreased by supply of
additional energy either as thermal, mechanical or electromagnetic field energy.
Other transmission properties, however, are unique for ionic conduction in
polyelectrolytes. (1) Current pulses injected into the filaments were transformed
into oscillating currents or even into several discrete charge pulses closely
resembling that of single-channel recordings. Discontinuous transmission is due
to the existence of counterion clouds along the fixed anionic charge centers of
the polymer, each acting as an "ionic capacitor". (2) The conductivity of linear
polyelectrolytes strongly decreases with the charge number of the counterions;
thus, Ca(2+)and Mg(2+)are effective modulator of charge transfer through linear
polyelectrolytes. Field-dependent formation of divalent cation plugs on either
side of the microvillar conduction line may generate the characteristic gating
behavior of cation channels. (3) Mechanical movement of actin filament bundles,
e.g. bending of hair cell microvilli, generates charge translocations along the
filament structure (mechano-electrical coupling). (4) Energy of external fields,
by inducing molecular dipoles within the polyelectrolyte matrix, can be
transformed into mechanical movement of the system (electro-mechanical coupling).
Because ionic transmission through linear polyelectrolytes is very slow compared
with electronic conduction, only low-frequency electromagnetic fields can
interact with the condensed counterion systems of linear polyelectrolytes. The
delineated characteristics of microvillar ion conduction are strongly supported
by the phenomenon of electro-mechanical coupling (reverse transduction) in
microvilli of the audioreceptor (hair) cells and the recently reported dynamics
of Ca(2+)signaling in microvilli of audio- and photoreceptor cells. Due to the
cell-specific expression of different types and combinations of ion channels and
transporters in the microvillar tip membrane of differentiated cells, the
functional properties of this cell surface organelle are highly variable serving
a multitude of different cellular functions including receptor-mediated effects
such as Ca(2+)signaling, regulation of glucose and amino acid transport, as well
as modulation of membrane potential. Even mechanical channel activation involved
in cell volume regulation can be deduced from the systematic properties of the
microvillar channel concept. In addition, the specific ion conduction properties
of microfilaments combined with their proposed role in Ca(2+)signaling make
microvilli the most likely cellular site for the interaction with external
electric and magnetic fields.
PMID- 11013116
TI - Regulation of platelet production: the normal response to perturbation and
cyclical platelet disease.
AB - An age-structured model for the regulation of platelet production is developed,
and compared with both normal and pathological platelet production. We consider
the role of thrombopoietin (TPO) in this process, how TPO affects the transition
between megakaryocytes of various ploidy classes, and their individual
contributions to platelet production. After the estimation of the relevant
parameters of the model from both in vivo and in vitro data, we use the model to
numerically reproduce the normal human response to a bolus injection of TPO. We
further show that our model reproduces the dynamic characteristics of autoimmune
cyclical thromobocytopenia if the rate of platelet destruction in the circulation
is elevated to more than twice the normal value.
PMID- 11013117
TI - A model of beta-cell mass, insulin, and glucose kinetics: pathways to diabetes.
AB - Diabetes is a disease of the glucose regulatory system that is associated with
increased morbidity and early mortality. The primary variables of this system are
beta-cell mass, plasma insulin concentrations, and plasma glucose concentrations.
Existing mathematical models of glucose regulation incorporate only glucose
and/or insulin dynamics. Here we develop a novel model of beta -cell mass,
insulin, and glucose dynamics, which consists of a system of three nonlinear
ordinary differential equations, where glucose and insulin dynamics are fast
relative to beta-cell mass dynamics. For normal parameter values, the model has
two stable fixed points (representing physiological and pathological steady
states), separated on a slow manifold by a saddle point. Mild hyperglycemia leads
to the growth of the beta -cell mass (negative feedback) while extreme
hyperglycemia leads to the reduction of the beta-cell mass (positive feedback).
The model predicts that there are three pathways in prolonged hyperglycemia: (1)
the physiological fixed point can be shifted to a hyperglycemic level (regulated
hyperglycemia), (2) the physiological and saddle points can be eliminated
(bifurcation), and (3) progressive defects in glucose and/or insulin dynamics can
drive glucose levels up at a rate faster than the adaptation of the beta -cell
mass which can drive glucose levels down (dynamical hyperglycemia).
PMID- 11013119
TI - Editorial
PMID- 11013120
TI - Pharmacologic relevance of K(+)Channel remodeling in atrial fibrillation.
PMID- 11013121
TI - Angiotensin II induces nuclear factor- kappa B activation in cultured neonatal
rat cardiomyocytes through protein kinase C signaling pathway.
AB - Rat neonatal ventricular cardiomyocytes (RNVM) possess G protein-coupled
AT(1)receptors for angiotensin II (AngII) that activate multiple intracellular
pathways. To elucidate potential signaling mechanisms involved, we focussed on
the nuclear transcription factor-kappa B (NF- kappa B) in RNVM culture. Using
specific antibody to NF- kappa Bp65, immunolocalization of NF- kappa B was
cytoplasmic in unstimulated cardiomyocytes, whereas NF- kappa B was translocated
into the RNVM nucleus in response to AngII. This translocation was inhibited in
the presence of calphostin C, a specific inhibitor of protein kinase C (PKC).
Western blot analysis showed an increase of NF- kappa B in AngII-stimulated
cardiomyocyte nuclear extracts as compared to controls. Biomolecular interaction
analysis (BIA analysis) of NF- kappa B activation showed that only AngII-nuclear
extracts bound to NF- kappa B consensus sequence with a high degree of affinity.
This DNA-binding capacity was completely lost in calphostin C-treated cells. At
transcriptional level in RNVM, AngII mediates the upregulation of matrix
gelatinase (MMP-9), which is totally inhibited by calphostin C treatment. In
conclusion, cardiomyocyte nuclear NF- kappa B translocation in response to Ang II
via PKC pathway activates cardiomyocyte-specific transcription of MMP-9 and may
activate transcription from responsive genes which are involved in cardiac
hypertrophy process and/or cardiac remodeling.
PMID- 11013122
TI - Neonatal mouse cardiac myocytes exhibit cardioprotection induced by hypoxic and
pharmacologic preconditioning and by transgenic overexpression of human Cu/Zn
superoxide dismutase.
AB - Although mouse models have been increasingly used for studies of cardiac
pathophysiology, there is little information regarding cultured murine cardiac
myocytes. Accordingly, we have developed a cell culture model of neonatal mouse
cardiac myocytes by modifying a protocol used to prepare neonatal rat myocytes.
The principal change is the substitution of cytosine arabinoside for
bromodeoxyuridine to prevent fibroblast proliferation. Neonatal murine myocytes
exhibited persistent spontaneous contraction and were viable for up to 14 days in
culture. By flow cytometry 85% of the cells were cardiac myocytes. In sparse
cultures (average cell density 259 cells/mm(2)), both hypoxic preconditioning
(n=5) and phenylephrine pretreatment (n=8) produced significant protection of
cardiac myocytes from cell death during a prolonged period of severe hypoxia
(<0.5% O(2)for 18-20 h, both P<0.05). The phenylephrine effect was inhibited by
the alpha(1)-adrenoceptor antagonist prazosin (n=4, P<0.05) and by an xi PKC
peptide antagonist (xi V1-2) coupled to a TAT peptide (n=5, P<0. 05).
Interestingly, the mixed alpha(1)- and beta -adrenoceptor agonist norepinephrine,
which stimulates hypertrophy as measured by(14)[C]phenylalanine incorporation in
neonatal rat cardiac myocytes, did not cause hypertrophy in mouse myocytes,
suggesting that the signaling pathways for myocardial protection and hypertrophy
are likely to be both divergent and species specific. In cardiac myocytes
prepared from transgenic mice either homozygous or heterozygous for human Cu/Zn
superoxide dismutase, there was protection from cell death (n=3) and restoration
of(14)[C]phenyl- alanine uptake (n=4) during prolonged hypoxia (1% O(2)for 3
days, both P<0.05). We conclude that this cellular model, which is relatively
simple to prepare, can be used for in-vitro examination of cardiac protection
induced by preconditioning agents, various transgenes, and potentially by
targeted gene deletions.
PMID- 11013123
TI - The stress-responsive MAP kinase p38 is activated by low-flow ischemia in the in
situ porcine heart.
AB - Stress-responsive p38 MAP kinase is activated by phosphorylation during global
and severe regional myocardial ischemia. However, it is unknown whether or not
moderate, low-flow ischemia also activates p38 MAP kinase. Therefore, we
investigated p38 MAP kinase activation in an established model of short-term
hibernation and stunning. In anesthetized swine, coronary blood flow into the
left anterior descending coronary artery was decreased in order to reduce
regional contractile function by identical with 50%. Transmural myocardial
biopsies were taken before (controls) and during ischemia as well as after
reperfusion. Creatine phosphate content, after an early ischemic reduction,
recovered to control values at 90 min ischemia. The expression of phospholamban,
SERCA2a, calsequestrin, and troponin inhibitor was unchanged under these
conditions (Northern and Western blotting). At 8 min of ischemia, however, p38
MAP kinase was activated to 221% of the pre-ischemic value as judged by its
elevated phosphorylation state. Then, it returned to control values by 85 min
ischemia. We conclude that low-flow ischemia transiently activates the stress
responsive p38 MAP kinase which might act to trigger cardioprotective events.
PMID- 11013124
TI - Pre-synaptic NO-cGMP pathway modulates vagal control of heart rate in isolated
adult guinea pig atria.
AB - The role of nitric oxide (NO) in the vagal modulation of heart rate (HR) is
controversial. We tested the hypothesis that NO acts via a pre-synaptic, guanylyl
cyclase (GC) dependent pathway. The effects of inhibiting NO synthase (NOS) and
GC were evaluated in isolated atrial/right vagal nerve preparations from adult
(550-750 g) and young (150-250 g) female guinea pigs. Levels of NOS protein were
quantified in right atria using Western blotting and densitometry. The non
specific NOS inhibitor N- omega -nitro- L -arginine (L -NA, 100 microM, n=5)
significantly reduced the negative chronotropic response to vagal nerve
stimulation (VNS) at 3 and 5 Hz in the adult guinea pig. This effect was reversed
with 1 m ML -arginine. Similar results were observed with the specific neuronal
NOS inhibitor vinyl-N5-(1-imino-3-butenyl)- L -ornithine (L -VNIO, 100 microM,
n=7). Inhibition of GC with 1H-(1,2,4)-oxadiazolo-(4, 3-a)-quinoxalin-1-one (ODQ,
10 microM, n=7) also significantly reduced the negative chronotropic response to
VNS at 3 and 5 Hz in adult guinea pigs. Neither L -NA (n=6), L -VNIO (n=5) nor
ODQ (n=6) changed the HR response to cumulative doses of carbamylcholine in adult
guinea pig atria suggesting that the action of NO is pre-synaptic. The HR
response to VNS was unaffected by L -NA (n=7) or ODQ (n=7) in young guinea pigs
and Western blot analysis showed significantly lower levels of nNOS protein in
right atria from young animals. These results suggest a pre-synaptic NO-cGMP
pathway modulates cardiac cholinergic transmission, although this may depend on
the developmental stage of the guinea pig.
PMID- 11013125
TI - CTGF expression is induced by TGF- beta in cardiac fibroblasts and cardiac
myocytes: a potential role in heart fibrosis.
AB - Connective tissue growth factor (CTGF) is a cysteine-rich protein induced by
transforming growth factor beta (TGF- beta) in connective tissue cells. CTGF can
trigger many of the cellular processes underlying fibrosis, such as cell
proliferation, adhesion, migration and the synthesis of extracellular matrix;
however, its role in acute and chronic cardiac injury is not fully understood.
Here, we show that TGF- beta is a specific inducer of CTGF expression in both
cardiac fibroblasts and cardiac myocytes. The activity of a CTGF promoter-based
reporter construct correlated with endogenous CTGF expression, suggesting that
TGF- beta induces CTGF expression most likely by activating its promoter.
Upregulation of CTGF coincided with an increase in fibronectin, collagen type I
and plasminogen activator inhibitor-1 production. Forskolin, a stimulator of
cyclic AMP, blocked TGF- beta induced CTGF expression and reduced the basal level
of CTGF, whereas an inhibitor that blocks the MAP kinase signaling pathway (PD
98059) significantly enhanced TGF- beta induced CTGF expression. Furthermore, we
found that both TGF- beta and CTGF mRNAs were significantly elevated in the left
ventricles and septa of rat hearts 2-16 weeks following myocardial infarction.
This correlated well with concomitant increases in fibronectin, and type I and
type III collagen mRNA levels in these animal hearts. Significant upregulation of
CTGF was also detected in human heart samples derived from patients diagnosed
with cardiac ischemia. Based on these findings, we propose that CTGF is an
important mediator of TGF- beta signaling in the heart and abnormal expression of
this gene could be used as a diagnostic marker for cardiac fibrosis.
PMID- 11013126
TI - Augmented expression of cardiotrophin-1 and its receptor component, gp130, in
both left and right ventricles after myocardial infarction in the rat.
AB - Cardiotrophin-1 (CT-1) is a potent cytokine that stimulates the assembly of
sarcomeric units in series in cardiomyocytes through gp130 signaling, resulting
in myocardial cell hypertrophy. To clarify the role of CT-1 and the gp130
signaling pathway during ventricular remodeling after myocardial infarction, we
examined the expression of CT-1 and gp130 in a rat model of myocardial
infarction. At 1, 3, 7, 14, 28 and 56 days (n=12 for each group) after ligation
of a coronary artery, tissue samples were obtained from infarct tissue, the
ventricular septum and the right ventricle. All animals developed large
myocardial infarctions, with infarct sizes ranging from 39.8% to 50.3%.
Progressive left ventricular dilatation and inadequate hypertrophy of the
surviving myocardium were confirmed by echocardiography. CT-1 and gp130 mRNA
levels were determined by semiquantitative reverse transcription-polymerase chain
reaction using 1 or 5 microg of total RNA followed by Southern blotting. The
densitometric analysis of the Southern blots revealed a significant increase in
CT-1 and gp130 mRNA levels (P<0.01) compared with those of the sham-operated rats
at 1, 3, 7, 14, 28 and 56 days post-infarct in the infarct area, the ventricular
septum (non-infarcted area) and right ventricle. The protein levels of CT-1 and
gp130, determined by Western blot analysis, were significantly increased (P<0.05)
compared with those of sham-operated rats, peaked during the acute stage and
declined thereafter in the three regions described above. Immunohistochemical
staining showed that CT-1 and gp130-immunoreactivities were detected in
cardiomyocytes and fibroblast-like cells and that the intensity of staining was
increased at 7 days post-infarct compared with that in sham-operated rats. An
augmented CT-1 and gp130 system thus appears to play an important role during
ventricular remodeling after myocardial infarction.
PMID- 11013127
TI - Role of cGMP-inhibited phosphodiesterase and sarcoplasmic calcium in mediating
the increase in basal heart rate with nitric oxide donors.
AB - Nitric oxide (NO) donors increase heart rate (HR) through a guanylyl cyclase
dependent stimulation of the pacemaker current I(f), without affecting basal I(Ca
L). The activity of I(f)is known to be enhanced by cyclic nucleotides and by an
increase in cytosolic Ca(2+). We examined the role of cGMP-dependent signaling
pathways and intracellular Ca(2+)stores in mediating the positive chronotropic
effect of NO donors. In isolated guinea pig atria, the increase in HR in response
to 1-100 micromol/l 3-morpholino-sydnonimine (SIN-1; with superoxide dismutase,
n=6) or diethylamine-NO (DEA-NO, n=8) was significantly attenuated by blockers of
the cGMP-inhibited phosphodiesterase (PDE3; trequinsin, milrinone or Ro-13-6438,
n=22). In addition, the rate response to DEA-NO or sodium nitroprusside (SNP) was
significantly reduced following inhibition of PKA (KT5720 or H-89, n=15) but not
PKG (KT5728 or Rp-8-pCPT-cGMPs, n=16). Suppression of sarcoplasmic (SR)
Ca(2+)release by pretreatment of isolated atria with ryanodine or cyclopiazonic
acid (2 micromol/l and 60 micromol/l, n=16) significantly reduced the
chronotropic response to 1-100 micromol/l SIN-1 or DEA-NO. Moreover, in isolated
guinea pig sinoatrial node cells 5 micromol/l SNP significantly increased
diastolic and peak Ca(2+)fluorescence (+13+/-1% and +28+/-1%, n=6, P<0.05). Our
findings are consistent with a functionally significant role of cAMP/PKA
signaling (via cGMP inhibition of PDE3) and SR Ca(2+)in mediating the positive
chronotropic effect of NO donors.
PMID- 11013128
TI - Transcriptional regulation of L-type calcium channel expression in cardiac
myocytes.
AB - The L-type calcium channel is a heteromultimeric protein complex, which is
expressed in the cardiac sarcolemma. Although post-translational regulation of
its subunits by protein kinase A (PKA) has been widely reported, little is known
about molecular processes that regulate expression of calcium channel subunits
(alpha(1C), alpha(2)- delta, and beta(2A)subunits). Previous studies from our
group demonstrate that the steady-state mRNA level of the alpha(1C)unit is
increased by treatment of myocytes with beta -adrenergic agonists. The current
study is designed to determine whether the mRNA levels for all subunits of the L
type calcium channel are coordinately controlled by a beta -adrenergic agonist,
and whether this occurs predominantly through control of rate of transcription.
Nuclear run-on assays were used to determine the transcription initiation rate of
these genes in cultured neonatal rat cardiac myocytes. In isoproterenol (10(-7)m)
treated myocytes, transcription of genes encoding the alpha(1C), alpha(2)- delta,
and beta(2A)subunits was enhanced. The increases in transcription initiation rate
for alpha(1C), alpha(2)- delta, and beta(2A)subunits genes were 404%, 367%, and
240% of control, respectively. Pretreatment with the beta -adrenergic antagonist
propranolol (10(-5)m) or PKA inhibitor H-89 (10(-6)m) blocked the effects of
isoproterenol, while either drug alone did not affect the gene transcription rate
significantly. Steady state mRNA levels of the subunits increased following
isoproterenol treatment. These results suggest that beta -adrenergic stimulation
and the PKA signaling pathway play an important role in transcriptional
regulation of the L-type calcium channel in myocyte. The expression of all the
subunits of this ion channel is under coordinate transcriptional control.
PMID- 11013129
TI - Activation of the Na(+)/H(+) exchanger is required for reperfusion-induced
Ins(1,4,5)P(3) generation.
AB - Post-ischemic reperfusion causes a change in inositol phosphate responses to
norepinephrine from primary generation of inositol(1,4) bis phosphate
(Ins(1,4)P(2)) to generation of inositol(1,4,5) tris phosphate (Ins(1,4,5)P(3))
that is required for the initiation of reperfusion arrhythmias. The current study
was undertaken to investigate the role of Na(+)/H(+)exchange in facilitating this
transient change in inositol phosphate response. Rat hearts were subjected to 20
min ischemia followed by 2 min reperfusion and Ins(1, 4,5)P(3)content was
measured by mass analysis or by anion-exchange HPLC following [(3)H]inositol
labeling. Reperfusion caused generation of [(3)H]Ins(1,4,5)P(3)(1732+/-398 to
3103+/-214, cpm/g tissue, mean+/-S.E.M., n=5, P<0.01) and the development of
arrhythmias. Inhibition of Na(+)/H(+)exchange, by reperfusing at pH 6.3 or by
pretreating with HOE-694 (10 n M-3 microM) or HOE-642 (3 microM) prevented the
[(3)H]Ins(1,4,5)P(3)generation, without causing any suppression of norepinephrine
release. Increases in Ins(1,4,5)P(3)mass were similarly reduced by inhibition of
Na(+)/H(+)exchange. Thus, activation of Na(+)/H(+)exchange is required for the
enhanced Ins(1,4,5)P(3)response observed under reperfusion conditions, and
prevention of Ins(1,4,5)P(3)generation may be an important contributor to the
anti-arrhythmic actions of inhibitors of Na(+)/H(+)exchange.
PMID- 11013130
TI - Metabolic inhibition activates a non-selective current through connexin
hemichannels in isolated ventricular myocytes.
AB - Intracellular Na(+)accumulation and K(+)loss play important roles in the
pathogenesis of arrhythmias and injury in the ischemic heart. We investigated the
role of metabolically sensitive connexin hemichannels as a potential route for
Na(+)influx and K(+)efflux during ischemia, using dye uptake and
electrophysiological measurements to assay hemichannel activity in isolated
rabbit ventricular myocytes. Consistent with the known size selectivity of
connexin hemichannels,;50% of myocytes exposed to either low extracellular
Ca(2+)(an established method for opening connexin hemichannels) or to metabolic
inhibitors (a recently described method for opening hemichannels) accumulated
fluorescent dyes with <1000 MW (propidium iodide and calcein), but excluded a
larger dye with 1500-3000 MW (dextran-rhodamine). Using the whole cell patch
clamp technique, we found that metabolic inhibitors activated a non-selective
current permeant to both small and large cations, and blocked by La(3+), similar
to the properties of connexin 43 when overexpressed in human embryonic kidney
(HEK) cells. These findings indicate that isolated cardiac myocytes endogenously
express metabolically-sensitive connexin hemichannels. If activated during
ischemia, these hemichannels could contribute significantly to altered ionic
fluxes promoting arrhythmias and myocardial injury.
PMID- 11013131
TI - Functional suppression of sodium channels by beta(1)-subunits as a molecular
mechanism of idiopathic ventricular fibrillation.
AB - Ventricular fibrillation leading to sudden cardiac death can occur even in the
absence of structural heart disease. One form of this so-called idiopathic
ventricular fibrillation (IVF) is characterized by ST segment elevation (STE) in
the electrocardiogram. Recently we found that IVF with STE is linked to mutations
of SCN5A, the gene encoding the cardiac sodium channel alpha -subunit. Two types
of defects were identified: loss-of-function mutations that severely truncate
channel proteins and missense mutations (e.g. a double mutation, R1232W and
T1620M) that cause only minor changes in channel gating. Here we show that co
expression of the R1232W+T1620M missense mutant alpha -subunits in a mammalian
cell line stably transfected with human sodium channel beta(1)-subunits results
in a phenotype similar to that of the truncation mutants. In the presence of
beta(1)subunits the expression of both ionic currents and alpha -subunit
specific, immunoreactive protein was markedly suppressed after transfection of
mutant, but not wild-type alpha -subunits when cells were incubated at
physiological temperature. Expression was partially restored by incubation at
reduced temperatures. Our results reconcile two classes of IVF mutations and
support the notion that a reduction in the amplitude of voltage-gated sodium
conductance is the primary cause of IVF.
PMID- 11013132
TI - The ultrarapid and the transient outward K(+) current in human atrial
fibrillation. Their possible role in postoperative atrial fibrillation.
AB - Atrial fibrillation (AF) causes distinct changes in atrial conduction,
characterized as electrical remodeling. Experimental data on the possible
significance of alterations of specific K(+)outward currents in this process are
still limited in human AF. The ultra-rapid delayed rectifier current (I(Kur)) has
not been studied in AF with respect to its sensitivity to 4-Aminopyridine (4-AP).
To clarify the role of (1) the 4-AP sensitive I(Kur)current, compared to
recordings without using 4-AP (I(Kur*)), and (2) the transient outward current
(I(to)) in changes of atrial repolarization associated with AF, whole cell
voltage-clamp recordings were obtained from atrial myocytes of patients
undergoing elective cardiac surgery, with and without a history of atrial
fibrillation (AF/non-AF). Further, a possible relation between experimental data
and postoperative AF was studied. In AF patients, I(Kur*)was reduced by 40%
[5.00+/-0.32 pA/pF (non-AF) and 2.91+/-0. 45 pA/pF (AF) at +50 mV, P<0.0001,
n=22/11], I(Kur)by 55% [3.81+/-0. 30 pA/pF (non-AF) and 1.71+/-0.20 pA/pF (AF) at
+50 mV, P<0.0001, n=22/11]. The mean amplitude of I(Kur)was significantly smaller
than I(Kur*). Consistently, I(to)was reduced by 44% [11.57+/-0.77 pA/pF (non-AF)
and 6.51+/-1.31 pA/pF (AF), P<0.01, n=25/11]. In 48% of non-AF patients,
postoperative AF was detected. The corresponding voltage-clamp recordings showed
a trend to reduced I(Kur*)and I(Kur)currents, although it did not reach
statistical significance. The consistent reduction of all three K(+)currents
investigated due to the presence of AF indicates an important association of
abnormalities in cellular repolarization with the onset and the self-sustaining
nature of human AF.
PMID- 11013133
TI - Inhibition of Na(+)/H(+) exchange at the beginning of reperfusion is
cardioprotective in isolated, beating adult cardiomyocytes.
AB - Stimulation of Na(+)/H(+)exchange during ischemia-reperfusion results in cardiac
damage. However, it is unclear whether the Na(+)/H(+)exchanger is active during
the ischemic period or during reperfusion. Adult beating cardiomyocytes were
exposed to an ischemia mimetic solution for 90 min and then reperfused with a
normal solution for 30 min. 5-(N,N-dimethyl)-amiloride (DMA), a blocker of the
Na(+)/H(+)exchanger, was administered during ischemia and the first 3 min of
reperfusion or only during the first 3 min of reperfusion. Administration of DMA
only upon reperfusion resulted in increased cell survival (81+/-1%, P<0.05)
compared to using the drug during ischemia and reperfusion (63+/-3%) and in the
absence of drug (60+/-1%). During ischemia, pH(i)was lower when DMA was present
in the ischemic solution. The inhibition of the Na(+)/H(+)exchanger retarded the
recovery of pH during reperfusion. The highest recovery of active cell shortening
was observed when DMA was used at the beginning of reperfusion. The use of DMA
also reduced the level of passive cell shortening during reperfusion, and when
used at the beginning of reperfusion significantly increased the recovery of
Ca(2+)transients. Our results demonstrate that the exchanger is primarily active
during reperfusion and that inhibition of the exchanger solely at this time has a
strong cardioprotective effect.
PMID- 11013134
TI - Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA
dehydrogenase deficiency: identification of a new enzyme defect, resolution of
its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in
isoleucine and valine metabolism.
AB - Acyl-CoA dehydrogenase (ACAD) defects in isoleucine and valine catabolism have
been proposed in clinically diverse patients with an abnormal pattern of
metabolites in their urine, but they have not been proved enzymatically or
genetically, and it is unknown whether one or two ACADs are involved. We
investigated a patient with isolated 2-methylbutyrylglycinuria, suggestive of a
defect in isoleucine catabolism. Enzyme assay of the patient's fibroblasts, using
2-methylbutyryl-CoA as substrate, confirmed the defect. Sequence analysis of
candidate ACADs revealed heterozygosity for the common short-chain ACAD A625
variant allele and no mutations in ACAD-8 but a 100-bp deletion in short/branched
chain ACAD (SBCAD) cDNA from the patient. Our identification of the SBCAD gene
structure (11 exons; >20 kb) enabled analysis of genomic DNA. This showed that
the deletion was caused by skipping of exon 10, because of homozygosity for a
1228G-->A mutation in the patient. This mutation was not present in 118 control
chromosomes. In vitro transcription/translation experiments and overexpression in
COS cells confirmed the disease-causing nature of the mutant SBCAD protein and
showed that ACAD-8 is an isobutyryl-CoA dehydrogenase and that both wild-type
proteins are imported into mitochondria and form tetramers. In conclusion, we
report the first mutation in the SBCAD gene, show that it results in an isolated
defect in isoleucine catabolism, and indicate that ACAD-8 is a mitochondrial
enzyme that functions in valine catabolism.
PMID- 11013135
TI - General equations for Pt, Ps, and the power of the TDT and the affected-sib-pair
test.
AB - Several equations are highlighted here, whose algebraic symmetries and generality
make them very useful for understanding and comparing the properties of the
transmission disequilibrium test (TDT) and affected sib-pair test. Methods using
the equations are also presented that yield precise estimates of sample sizes
needed for genome scans or for testing a single candidate gene, and these power
methods are shown to compare favorably with alternative approaches recently
described by Knapp (1999) and by Tu and Whittemore (1999). Simple relationships
are also noted that summarize the relative sample sizes required for equivalent
power to detect association by the TDT or case-control designs. As single
nucleotide polymorphism (SNP) maps revolutionize the search for disease-causing
genes, the equations should prove useful for planning and evaluating studies of
linkage and association across a broad range of possible disease models and
relationships between markers and linked disease loci.
PMID- 11013136
TI - Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with
neonatal-onset hepatic failure and encephalopathy.
AB - Cytochrome c oxidase (COX) catalyzes both electron transfer from cytochrome c to
molecular oxygen and the concomitant vectorial proton pumping across the inner
mitochondrial membrane. Studying a large family with multiple cases of neonatal
ketoacidotic comas and isolated COX deficiency, we have mapped the disease locus
to chromosome 17p13.1, in a region encompassing two candidate genes involved in
COX assembly-namely, SCO1 and COX10. Mutation screening revealed compound
heterozygosity for SCO1 gene mutations in the patients. The mutated allele,
inherited from the father, harbored a 2-bp frameshift deletion (DeltaGA; nt 363
364) resulting in both a premature stop codon and a highly unstable mRNA. The
maternally inherited mutation (C520T) changed a highly conserved proline into a
leucine in the protein (P174L). This proline, adjacent to the CxxxC copper
binding domain of SCO1, is likely to play a crucial role in the tridimentional
structure of the domain. Interestingly, the clinical presentation of SCO1
deficient patients markedly differs from that of patients harboring mutations in
other COX assembly and/or maturation genes.
PMID- 11013137
TI - Cloning of the gene encoding a novel integral membrane protein, mucolipidin-and
identification of the two major founder mutations causing mucolipidosis type IV.
AB - Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder
characterized by severe psychomotor retardation and ophthalmologic abnormalities,
including corneal opacity, retinal degeneration, and strabismus. Unlike the
situation in other lysosomal disorders, the accumulation of heterogeneous storage
material observed in MLIV does not result from a block in the catabolic pathways
but is due to an ill-defined transport defect in the late steps of endocytosis.
With the aim of cloning the MLIV gene, we searched in the 19p13.2-13.3 region,
where the locus previously had been assigned by linkage mapping. In this region,
we have identified a novel gene that is mutated in all patients with MLIV who
were enrolled in our study. One patient was homozygous for the splice-acceptor
mutation, and another was homozygous for a deletion removing the first six exons
of the gene. In addition, four compound heterozygotes for these two mutations
were identified. Haplotype analysis indicates that we have identified the two
major founder mutations, which account for >95% of MLIV chromosomes in Ashkenazi
Jewish patients. The gene, ML4, encodes a protein named "mucolipidin, " which
localizes on the plasma membrane and, in the carboxy-terminal region, shows
homologies to polycystin-2, the product of the polycystic kidney disease 2 gene
(PKD2) and to the family of transient receptor potential Ca(2+) channels.
Mucolipidin is likely to play an important role in endocytosis.
PMID- 11013145
TI - [Recent transmission of tuberculosis in Madrid (Spain): usefulness of molecular
techniques].
AB - BACKGROUND: Recent studies suggest that many tuberculosis cases in urban areas
result from recent transmission. The aim of this study was to determine patterns
of tuberculosis transmission in Madrid. PATIENTS AND METHODS: A prospective
population-based molecular epidemiological study of patients diagnosed of
tuberculosis was conducted in three urban districts of Madrid (455.050
inhabitants) during 1997-1998. Clinical, demographic and epidemiological data
were reviewed. Patients were included in clusters when their isolates contained:
a) six or more IS6110 bands in an identical pattern, or b) five or fewer IS6110
bands that matched identically and had an identical spoligotyping pattern.
RESULTS: Of 207 positive-culture patients, 148 (71,5%) were DNA fingerprinted. A
total of 18 clusters which included 62 patients (41,9%) were identified. Clusters
contained between 2 and 12 cases. Risk factors for clustering included: age < 35
years (OR = 4,1, 95% CI: 1,9-8,9), injection drug use (OR = 4,7, 95% CI: 1,6
14,8), HIV infection (OR = 2,7, 95% CI: 1,1-6,8), and a history of imprisonment
(OR = 2,9, 95% CI: 1,2-7,2). The epidemiological investigation identified
connections among 27% of clustered patients. CONCLUSIONS: A high proportion of
cases of tuberculosis in urban Madrid result from recent transmission. Molecular
epidemiology studies give valuable information for urban tuberculosis control.
PMID- 11013146
TI - [Transmission of tuberculosis in the prisons of Madrid].
AB - BACKGROUND: Prisons are recognized as high-risk settings for tuberculosis
transmission. The purpose of this study was to describe the characteristics of
prisoners with tuberculosis and to determine the extent of transmission of
tuberculosis in the prison population of Madrid. PATIENTS AND METHODS: Patients
with positive culture for Mycobacterium tuberculosis between 1997 and 1998 from
the prison system of Madrid were included. The medical records for these patients
were reviewed, and they were also interviewed. Patients were included in clusters
when their isolates contained 1) six or more IS6110 bands in an identical pattern
or 2) five or fewer IS6110 bands that matched identically and had an identical
spoligotyping pattern. RESULTS: Culture-proven tuberculosis was diagnosed in 97
prisoners (case rate: 693 per 100.000 per year). Isolates from 73 (75%) patients
were available for fingerprinting. The mean age of these patients was 33 yr (SD:
6,9), 92% were male, and 14% were immigrants. Seventy-one percent (71%) of
patients were HIV-positive, 32% were active intravenous drug users and 70%
nonintravenous drug users in the last two years. Primary drug resistance to
isoniazid was 1,8%. Forty-one percent of prisoners (41%) were grouped in 9
clusters. Epidemiological links were found in 37% of clustered patients. Risk
factors for clustering were not detected. CONCLUSION: The results suggest recent
transmission of tuberculosis in the prisons of Madrid. It is essential that
correctional facilities comply fully with the recomendations for prevention and
control of tuberculosis.
PMID- 11013147
TI - [Injury rate and incidence of accidents with biological risk among infirmary
students].
AB - BACKGROUND: A study of the incidence and characteristics of biological accidents
among infirmary students during their practicals at the hospital. MATERIAL AND
METHOD: A retrospective study carried out at five centres by means of two
questionnaires, one on the duration of the training and the rate of accidents and
the other on the characteristics, precautions and ports exposure behaviour.
RESULTS: Out of 397 students, 70,5% had accidents at a rate of 64% (CI 95%, 59
68). Of these, 15% were accidents with biological risk, the majority being jabs
(39%) and splashes (32,5%). It is worth note that 49,2% occurred while putting
away the material and 58% in the absence of any individual protective measures.
One out of 8 accidents implied a biological risk. CONCLUSIONS: A very high rate
of accidents was observed with important deficiencies in security.
PMID- 11013148
TI - [Prevalence and incidence of hepatitis A in patients with hepatitis B and C].
AB - BACKGROUND: Patients with chronic hepatitis are in risk to acquire a fulminant
hepatitis associated with hepatitis A virus superinfection. PATIENTS AND METHODS:
Antibodies against hepatitis A were study in serum from 353 patients with chronic
hepatitis B or C. RESULTS: The prevalence of IgG-HAV antibodies was 81% in
chronic hepatitis C patients, and 77% in chronic hepatitis B patients. The
presence of anti-HAV antibodies was related to the patients' age. None case of
acute hepatitis A in chronic hepatitis patients was detected. CONCLUSIONS: The
prevalence of anti-HAV antibodies is high in patients with chronic viral
hepatitis but the incidence of the disease is low. Hepatitis A vaccination should
do with previously screening.
PMID- 11013149
TI - [Tuberculosis, recent transmission and prisons].
PMID- 11013150
TI - [Tools for the practice of evidence based medicine (I). Update in evidence based
information resources for clinical practice].
PMID- 11013151
TI - [On the revalidation for doctors in Spain].
PMID- 11013152
TI - [Diagnosis and treatment of myasthenia gravis].
PMID- 11013153
TI - [Abdominal pain and diarrhoea in a 33 year-old man].
PMID- 11013154
TI - [Consensus document on the prevention and control of tuberculosis in Spain].
PMID- 11013155
TI - [Methodological considerations about the prevalence of eating disorders].
PMID- 11013156
TI - [Reply] [In Process Citation]
PMID- 11013157
TI - [Neuroleptic malignant syndrome and atypical antipsychotics].
PMID- 11013158
TI - [ [In Process Citation]
PMID- 11013159
TI - Author's reply
PMID- 11013160
TI - Low-cost high-volume ECCE with PC I0L
PMID- 11013161
TI - Low-cost high-volume ECCE with PC I0L.
AB - The following two letters address an article that appeared in the October 1999
issue of the Journal: Ruit S, Tabin GC, et al. Low-cost high-volume extracapsular
cataract extraction with posterior chamber intraocular lens implantation in
Nepal. (Ophthalmology 1999;106:1887-92)
PMID- 11013163
TI - Author's reply
PMID- 11013162
TI - Carotid artery compression of the optic nerve.
PMID- 11013165
TI - Authors' reply
PMID- 11013164
TI - Author's reply
PMID- 11013166
TI - Long-term follow-up of retinal detachment from macular hole.
PMID- 11013167
TI - LASIK after penetrating keratoplasty.
PMID- 11013168
TI - Study of the AMO ARRAY silicone lens and a monofocal IOL.
PMID- 11013170
TI - Author's reply
PMID- 11013169
TI - Detection of choroidal calcium by CT scan.
PMID- 11013171
TI - Corneal thickness and measured IOP.
PMID- 11013172
TI - Author's reply
PMID- 11013173
TI - Intracameral lidocaine in routine phacoemulsification.
PMID- 11013174
TI - Authors' reply
PMID- 11013175
TI - Author's reply
PMID- 11013176
TI - Accurate intraocular pressure measurement-the myth of modern ophthalmology?
PMID- 11013177
TI - If intraocular pressure measurement is only an estimate-then what?
PMID- 11013178
TI - Mapping the visual field to the optic disc in normal tension glaucoma eyes.
AB - PURPOSE: To establish the anatomical relationship between visual field test
points in the Humphrey 24-2 test pattern and regions of the optic nerve head
(ONH) DESIGN: Cross-sectional study. PARTICIPANTS: Glaucoma patients and suspects
from the Normal Tension Glaucoma Clinic at Moorfields Eye Hospital. METHODS:
Sixty-nine retinal nerve fiber layer (RNFL) photographs with well-defined RNFL
defects and/or prominent bundles were digitized. An appropriately scaled Humphrey
24-2 visual field grid and an ONH reference circle, divided into 30 degrees
sectors, were generated digitally. These were superimposed onto the RNFL images.
The relationship of visual field test points to the circumference of the ONH was
estimated by noting the proximity of test points to RNFL defects and/or prominent
bundles. The position of the ONH in relation to the fovea was also noted. MAIN
OUTCOME MEASURES: The sector at the ONH corresponding to each visual field test
point, the position of the ONH in relation to the fovea, and the effect of the
latter on the former. RESULTS: A median 22 (range, 4-58), of a possible 69, ONH
positions were assigned to each visual field test point. The standard deviation
of estimations was 7.2 degrees. The position of the ONH was 15.5 degrees
(standard deviation 0.9 degrees ) nasal and 1.9 degrees (standard deviation 1.0
degrees ) above the fovea. The location of the ONH had a significant effect on
the corresponding position at the ONH for 28 of 52 visual field test points.
CONCLUSIONS: A clinically useful map that relates visual field test points to
regions of the ONH has been produced. The map will aid clinical evaluation of
glaucoma patients and suspects, as well as form the basis for investigations of
the relationship between retinal light sensitivity and ONH structure.
PMID- 11013179
TI - Accuracy of clinical estimates of intraocular pressure in Chinese eyes.
AB - PURPOSE: To investigate the validity of clinical estimates of intraocular
pressure (IOP) in Chinese people. DESIGN: Prospective, cross-sectional, hospital
based in vivo study. PARTICIPANTS: Twenty-three ethnic Chinese adults (aged 35-82
years) undergoing routine phacoemulsification surgery were examined. TESTING:
"True" IOP was measured with a solid-state hemodynamic monitor through a cannula
in the anterior chamber. IOP was set successively to 10, 20, and 30 mmHg in each
subject, using a reservoir of balanced salt solution. Intraocular pressure was
simultaneously estimated by use of a hand-held applanation tonometer (Perkin's)
and a Tono-Pen. The association between ocular biometric variables and
measurement error was examined. MAIN OUTCOME MEASURES: The median of three
readings at each IOP level was taken as the IOP estimate of each instrument.
Measurement error was calculated as the mean difference (tonometer minus direct
measurement). RESULTS: The error for the hand-held applanation tonometer was
1.6, -4.3 and -5.7 at 10, 20, and 30 mmHg, respectively. For the Tono-Pen the
measurement error was +0.4, -2.0, and -4.1 at 10, 20, and 30 mmHg, respectively.
We could identify no association between measurement error and corneal thickness
or curvature, anterior chamber depth, or axial length. CONCLUSIONS: The
applanation tonometer and Tono-Pen underestimate the true IOP in Chinese eyes.
Error increases as true IOP increases. These tonometers do not give an accurate
estimate of IOP in East Asians.
PMID- 11013180
TI - Long-term follow-up of trabeculectomy with intraoperative 5-fluorouracil for
uveitis-related glaucoma.
AB - PURPOSE: To determine the effect of intraoperative application of 5-fluorouracil
(5-FU) on the long-term outcome of trabeculectomy in uveitis-related glaucoma.
DESIGN: An open, prospective, noncomparative case study to evaluate the use of
intraoperative application for 5 minutes of 25 mg/ml 5-FU in primary
trabeculectomy for uveitis-related glaucoma. PARTICIPANTS: Fifty eyes of 43
consecutive patients were enrolled in the study. METHODS: Data were recorded
prospectively on specifically designed forms at visits every 3 months after
surgery. MAIN OUTCOME MEASURES: The intraocular pressure, need for additional
medication, and the need for repeat surgery were the criteria that determined the
outcome of surgery. RESULTS: No significant intraoperative, postoperative, or
late complications of 5-FU administration were noted. Successful filtration was
achieved in 82% of eyes at 1 and 2 years after surgery. The success rate was 67%
at 5 years. Failure was significantly more common and occurred earlier in
patients of black ethnic origin. No deleterious effect on control of uveitis in
relation to surgical intervention was observed. CONCLUSIONS: Intraoperative
application of 5-FU appears to be a long-term, safe, and effective adjunct to
trabeculectomy in uveitis-related glaucoma.
PMID- 11013181
TI - Management of alkali burns : an 11-year retrospective review.
AB - OBJECTIVE: To review the spectrum of patients with alkali burns admitted over an
11-year period and to assess the clinical outcomes after the introduction of a
standard alkali burn treatment protocol. DESIGN: Retrospective nonrandomized
comparative study. PATIENTS AND INTERVENTIONS: A total of 121 patient records
with alkali burns (n = 177 eyes) admitted to a tertiary hospital between 1987 and
1998 were reviewed. Eyes treated with a standard alkali burn treatment protocol,
which included intensive topical steroids, ascorbate, citrate, and antibiotics,
were compared with eyes treated by conservative management with antibiotics, and
a short course of steroids. MAIN OUTCOME MEASURES: Time to corneal
reepithelialization, final best-corrected visual acuity, and time to visual
recovery, length of hospital stay, and complications were analyzed. RESULTS: The
standard protocol tended to delay corneal reepithelialization by one day (P: =
not significant) in eyes with grade 1 burns (n = 76) and by 2 days (P: = 0.04) in
grade 2 burns (n = 52), with no difference in final visual outcome. There were 37
eyes with grade 3 burns. Those treated with the standard protocol showed a trend
toward more rapid corneal reepithelialization. Twenty-seven of 29 (93%) eyes with
grade 3 injuries achieved a final best-corrected visual acuity of 20/40 or better
compared with 3 of 6 (50%) eyes not treated according to the standard protocol
(P: = 0.02). Eyes with grade 4 burns (n = 12), whether treated with the standard
protocol or not, required 10 to 12 weeks for corneal reepithelialization. There
was no statistically significant difference in final visual acuity. CONCLUSIONS:
On the basis of our findings, a number of recommendations can be made for the
management of alkali injuries. Patients with a grade 1 or 2 injury do not require
routine admission and do not benefit from the use of intensive treatment with
ascorbate and citrate. A trend toward more rapid healing and a better final
visual outcome were apparent in grade 3 burns, but our standard protocol made no
difference in grade 4 burns.
PMID- 11013182
TI - Surgical treatment of advanced pellucid marginal degeneration.
AB - PURPOSE: To determine the efficacy of simultaneous peripheral crescentic lamellar
keratoplasty (LK) and central penetrating keratoplasty (PK) for advanced pellucid
marginal degeneration (PMD). DESIGN: Retrospective, noncomparative,
interventional case series. PARTICIPANTS: Five patients with advanced PMD.
METHOD: Simultaneous peripheral crescentic LK and central PK followed by
selective suture removal and astigmatic keratotomy in the postoperative period.
MAIN OUTCOME MEASURES: These included interval of time required for visual
rehabilitation, best spectacle-corrected visual acuity achieved, and amount of
corneal astigmatism, as measured by videokeratography. Measuring the change in
corneal astigmatism by videokeratography over the subsequent follow-up period
after spectacle correction had been prescribed assessed stability of the achieved
refraction. RESULTS: Visual acuity results were 20/40 in three eyes, 20/80 in one
eye, and 20/400 in one eye. The latter two had decreased acuity from posterior
subcapsular cataract formation, which may have been caused by topical steroid
use. The time required for visual rehabilitation ranged from 5.13 to 10.93 (mean,
9.92) months, and the amount of corneal astigmatism at the end of this period
ranged from 0.3 diopters (D) to 5.3 D. A tendency for an increase in "with the
rule astigmatism" after the rehabilitation period was noted. Two patients had
elevations of intraocular pressure that responded to reduction in topical steroid
dose. CONCLUSIONS: The short-term results with this technique are excellent in
that it provides early and stable visual rehabilitation in patients with advanced
PMD. Low to moderate levels of postkeratoplasty astigmatism were achieved in all
the eyes treated. The usual tendency of an increase in "against the rule
astigmatism" that occurs when PK alone is done for PMD was eliminated.
PMID- 11013183
TI - Flow cytometric analysis of conjunctival epithelium in ocular rosacea and
keratoconjunctivitis sicca.
AB - PURPOSE: To investigate by flow cytometry and impression cytology (IC) specimens
the inflammatory status of the conjunctival epithelium and goblet cell density in
two series of patients with rosacea and dry eye syndrome compared with a
population of healthy subjects. DESIGN: Nonrandomized, prospective, comparative
case series. PARTICIPANTS: Twenty-six eyes of 13 patients with rosacea, 26 eyes
of 13 patients with dry eye syndrome, and 24 eyes of 12 control subjects were
included in this study. METHODS: IC specimens were collected after clinical
examination of the ocular surface and analyzed by flow cytometry, using
antibodies directed to human lymphocyte antigen-DR (HLA-DR), intercellular
adhesion molecule-1 (ICAM-1) (CD 54), and the peptidic core of the conjunctival
mucin (M1/MUC5AC). The percentage of positive cells was calculated and levels of
fluorescence expression quantified and compared with those obtained in a series
of 12 healthy subjects. MAIN OUTCOME MEASURES: Tear break-up time (TBUT),
Schirmer test, fluorescein and lissamin green stainings, and IC were realized in
this study. RESULTS: A significant increase of HLA-DR and ICAM-1 expressions by
epithelial cells was consistently found in the two pathologic groups compared
with levels calculated in normal eyes. The two markers were well correlated with
each other and inversely with TBUT and Schirmer test. The percentage of goblet
cells was significantly decreased in rosacea patients and in dry eye patients
compared with the normal group with a significant negative correlation with both
HLA DR and ICAM-1 markers. CONCLUSIONS: Ocular rosacea and keratoconjunctivitis
sicca were associated with severe ocular surface changes, such as an
overexpression of inflammatory markers and a significant decrease in the number
of goblet cells.
PMID- 11013185
TI - Discussion by herbert E. Kaufman, MD
PMID- 11013184
TI - Preliminary clinical results of posterior lamellar keratoplasty through a
sclerocorneal pocket incision.
AB - PURPOSE: To report the preliminary results of a surgical technique for
transplantation of posterior corneal tissue through a sclerocorneal pocket
incision for corneal endothelial disorders. DESIGN: Retrospective,
noncomparative, interventional cases series. PARTICIPANTS AND INTERVENTION: In
seven sighted human eyes, a deep stromal pocket was created across the cornea
through a 9.0-mm superior scleral incision. A 7.0- or 7.5-mm diameter, posterior
lamellar disc was excised and replaced by a 'same size' donor posterior disc,
without suture fixation. The scleral incision was sutured. MAIN OUTCOME MEASURES:
Intra- and postoperative complications, best spectacle-corrected visual acuity,
keratometry, topography, biomicroscopy, pachymetry, and endothelial cell density
were evaluated. RESULTS: Six to 12 months after surgery, all transplants were
clear and in position. Best spectacle-corrected visual acuity was limited by
preexisting maculopathies in two eyes and varied from 20/80 to 20/20.
Postoperative astigmatism averaged 1. 54 diopters (D; standard deviation [SD] +/-
0.81 D), pachymetry averaged 0.49 mm (SD +/- 0.09 mm), and postoperative
endothelial cell density averaged 2520 cells/mm(2) (SD +/- 340 cells/mm(2)). In
one eye, a microperforation occurred during stromal pocket dissection so that the
procedure was converted into a penetrating keratoplasty. CONCLUSIONS: Posterior
lamellar keratoplasty through a sclerocorneal pocket incision is a feasible
surgical approach to manage corneal endothelial disorders.
PMID- 11013187
TI - Discussion by stephen trokel, MD
PMID- 11013186
TI - Early results of hyperopic and astigmatic laser in situ keratomileusis in eyes
with secondary hyperopia.
AB - PURPOSE: To assess the safety and efficacy of laser in situ keratomileusis
(LASIK) for secondary hyperopia and hyperopic astigmatism and to develop a VISX
STAR S2 LASIK nomogram (VISX Inc., Santa Clara, CA) for consecutive hyperopia
after prior myopic refractive surgery. DESIGN: Prospective, nonrandomized, self
controlled interventional study. PARTICIPANTS: Thirty patients with consecutive
hyperopia or hyperopia and astigmatism after LASIK, photorefractive keratectomy,
automated lamellar keratoplasty, or radial keratotomy. INTERVENTION/METHODS:
Prospective evaluation of LASIK in 30 secondary eyes with fogged manifest sphere
from +0.5 to +6.0 diopters (D) and cylinder from 0 to +5.0 D. MAIN OUTCOME
MEASURES: Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA),
and spherical equivalent (SE). RESULTS: Mean manifest SE was +1.73 +/- 0.79 D
before surgery, -0.13 +/- 1.00 D at 6 months after surgery, and -0.18 +/- 1.08 D
at 1 year after surgery. At 6 months, 84% of patients with secondary hyperopia
had UCVA of 20/40 or better; 76% were within +/-1 D of emmetropia. At 1 year, 85%
had UCVA of 20/40 or better and 85% were within +/-1 D of emmetropia. No patients
with secondary hyperopia lost 2 or more lines of BCVA at 1 year. Complications
included intraoperative bleeding (3.3%), intraoperative epithelial defect (3.3%),
transient interface debris (3.3%), significant dry eye (3.3%), blood in interface
(3.3%), irregular astigmatism (6.7%), slight decentration (6.7%), trace haze
(6.7%), or mild epithelial ingrowth not requiring removal (3.3%). CONCLUSIONS:
These early data suggest that LASIK for consecutive hyperopia from +0.5 to +5.50
D and astigmatism from 0 to +2.75 D using the VISX STAR S2 benefits from a
nomogram adjusted for preoperative refraction, age, and prior refractive surgery,
and is safe and effective.
PMID- 11013188
TI - Contrast sensitivity evaluation after laser in situ keratomileusis.
AB - OBJECTIVE: To determine the effects of laser in situ keratomileusis (LASIK) on
best-corrected visual acuity (BCVA) and contrast sensitivity. DESIGN:
Prospective, observational case series. PARTICIPANTS: One hundred twelve eyes, in
65 patients with myopia and myopia with astigmatism, who underwent LASIK. TESTING
AND MAIN OUTCOME MEASURES: Best-corrected visual acuity using the Snellen visual
acuity chart and contrast sensitivity using the CSV 1000 (Vector Vision, Dayton
OH) was tested before surgery and 1 week, 1 month, and 3 months after surgery in
patients who underwent LASIK. RESULTS: Contrast sensitivity was depressed for
patient eyes with spherical equivalence (SE) between -1.25 diopters (D) and
13.75 D, at 12 cycles/degree for at least 3 months and at 18 cycles/degree for 1
week after LASIK. For patient eyes with SE between -1.25 D and -6.00 D, contrast
sensitivity was depressed only at 12 cycles/degree for at least 3 months after
LASIK. For patient eyes with SE between -6.00 D and -13.75 D, contrast
sensitivity was depressed at 6, 12, and 18 cycles/degree 1 week after LASIK but
returned toward preoperative levels by 1 month after surgery. Despite the slight
decreases in contrast sensitivity, all scores were still within the range of
normal values except for 12 cycles/degree for 3 months and 18 cycles/degree at 1
week after surgery in the high myopia group. Although highly myopic patients,
compared with patients with low myopia, had slightly less BCVA before surgery,
both groups maintained their preoperative BCVA at all postoperative visits.
CONCLUSIONS: Based on this study, we conclude that LASIK has little effect on
BCVA and contrast sensitivity for up to 3 months after surgery.
PMID- 11013190
TI - Discussion by allan E. Kolker, MD
PMID- 11013189
TI - Posterior capsular opacification in phacotrabeculectomy : a long-term comparative
study of silicone versus acrylic intraocular lens.
AB - PURPOSE: To investigate the long-term outcomes of silicone versus acrylic
intraocular lens (IOL) implantation in phacotrabeculectomy (PT) with special
emphasis on posterior capsular opacification. DESIGN: Long-term follow-up on
prior 1-year prospective, randomized study. PARTICIPANTS: A total of 200 eyes of
200 consecutive primary open-angle glaucoma patients who had undergone primary PT
with capsular bag implantation of either a silicone IOL (102 eyes) or an acrylic
IOL (98 eyes) according to the initial short-term prospective, randomized study
protocol. INTERVENTION: The study eyes underwent primary trabeculectomy,
phacoemulsification, and posterior chamber IOL implantation. Adjunctive mitomycin
C was used selectively, primarily in patients with one or more risk factors for
filtration failure. MAIN OUTCOME MEASURES: Incidence of posterior capsular
opacification (PCO), best-corrected visual acuity (BCVA), intraocular pressure
(IOP), number of pressure-lowering medications, and filtration success rates,
defined as maintenance of target IOP while on one (criteria 1) or zero (criteria
2) pressure-lowering medications without further surgical intervention. RESULTS:
At 3-year follow-up, the PCO rate and BCVA did not differ significantly between
the two groups (P: > 0.05 for both). In addition, there were no significant
differences in IOP, number of medications, and filtration success rate between
the two groups (P: > 0.05 for each). CONCLUSIONS: There were no significant long
term differences between the silicone and acrylic IOL groups in PCO, BCVA, IOP,
number of medications, and success of filtration surgery after PT. Both groups
attained significant improvement in BCVA and IOP control after surgery.
PMID- 11013191
TI - Pediatric orbital floor fracture : direct extraocular muscle involvement.
AB - OBJECTIVE: To study the clinical presentation, operative findings, and
postoperative results of a surgical series of isolated orbital floor fractures in
children. DESIGN: Noncomparative, retrospective, consecutive case series.
PARTICIPANTS: Thirty-four patients (34 orbits) less than 18 years of age with
isolated orbital floor fractures. Indications for surgery were severe limitation
of extraocular ductions, 22 of 34; enophthalmos, 8 of 34: or both, 4 of 34.
INTERVENTION: Surgical repair. MAIN OUTCOME MEASURES: Cause of fracture,
symptoms, clinical signs, radiographic data, operative findings, postoperative
results, and complications. RESULTS: Children older than 12 years of age were
more likely to sustain an orbital floor fracture as a result of interpersonal
violence than were children less than 12 years of age (P: = 0.020). Sixty-two
percent of patients (21 of 34) exhibited pain with eye movements and/or nausea
and vomiting. Most had a trapdoor type fracture (21 of 34). The inferior rectus
muscle was entrapped in the orbital floor fracture in 69% (18 of 26) of patients
with a severe limitation of ocular ductions. Preoperative nausea and vomiting
were immediately relieved after surgery. The median time for improvement of
preoperative duction deficits and diplopia was 4 days for patients receiving
surgery within 7 days and 10.5 days for those undergoing surgery after 14 days
(P: = 0.030). Resolution of duction deficits or diplopia was not dependent on
time of surgery if performed within 1 month of injury. Loss of vision, worsening
of motility, or implant complications did not occur. CONCLUSIONS: Pediatric
patients with isolated orbital floor fractures who had pain, nausea, vomiting,
and severe limitation of extraocular motility often have direct entrapment of the
inferior rectus muscle into the fracture site. Surgical repair rapidly relieved
preoperative pain, nausea, and vomiting. For patients with severe limitation of
ductions, early surgical repair within 7 days of injury resulted in more rapid
improvement of ductions and diplopia than surgery performed later.
PMID- 11013192
TI - Restoration of fusion in children with intracranial tumors and incomitant
strabismus.
AB - PURPOSE: Intracranial tumors may cause eye misalignment and interruption of
sensory fusion. The ocular misalignment may be permanent or may be corrected
after tumor treatment with or without specific strabismus treatment. This report
analyzes the binocular vision outcome of children with misaligned eyes from brain
tumors who regain orthotropia. DESIGN: A retrospective noncomparative case
series. PARTICIPANTS: Twenty-three surviving children less than 18 years of age
with a new heterotropia and absence of fusion associated with the development of
a brain tumor. INTERVENTIONS: Tumor resection/radiation/chemotherapy and
necessary strabismus management. MAIN OUTCOME MEASURE: Stereopsis (>/= 4 of 10
circles) measured with the Randot II stereo test at near fixation. RESULTS:
Fourteen children regained orthotropia either after tumor therapy, strabismus
treatment, or both. Ten of these 14 children with realigned vision regained high
grade stereovision. Nine patients did not regain orthotropia and were excluded.
The mean age at tumor diagnosis of the fusing group was 9.9 years (range, 3-17
years) compared with 8.5 years (range, 6-12 years) in the four realigned
nonfusing patients. The mean duration of misalignment was 12 months (range, 2-51
months) for the fusing group, and 45 months (range, 14-120 months) for the
nonfusing group. CONCLUSIONS: Children and adolescents with brain tumor
associated eye misalignment may regain the ability to fuse if their misalignment
can be corrected. An improved prognosis was noted for those patients when the
misalignment had been present for a shorter duration. These data suggest that the
outcome may be better for incomitant strabismus than that reported for acute
comitant esotropia.
PMID- 11013193
TI - Efficacy of diclofenac versus dexamethasone for treatment after strabismus
surgery.
AB - OBJECTIVE: To compare the efficacy of topical diclofenac sodium 0.1% versus
dexamethasone 0.1% on the conjunctival healing process and on intraocular
pressure (IOP) after strabismus surgery. DESIGN: A randomized clinical trial.
PARTICIPANTS: Forty consecutive pediatric patients who underwent strabismus
surgery. INTERVENTION: The patients were assigned before surgery to receive
topical diclofenac 0.1% (study group, 20 patients) or dexamethasone 0.1% (control
group, 20 patients) from immediately after surgery to up to 4 weeks after surgery
(both combined with chloramphenicol 0.2%, polymyxin B sulfate 2500 U). MAIN
OUTCOME MEASURES: Between-group comparison of five parameters: patient
discomfort, conjunctival chemosis, inflammation, gap, and intraocular pressure
(IOP) at 1, 2, and 4 weeks after surgery. RESULTS: At postoperative week 2, the
diclofenac-treated group showed significantly less patient discomfort and less
conjunctival inflammation, edema, and gap than the dexamethasone group (P: =
0.003, P: = 0.04, P: = 0.02, P: = 0. 001, respectively). At week 4, the study
patients continued to show less discomfort and conjunctival gap (P: = 0.02). The
dexamethasone group showed a significant change in IOP between the preoperative
and the fourth postoperative week (P: = 0.001 in the right eye, P: = 0.0005 in
the left eye) and an increased prevalence of higher IOP during the fourth
postoperative week (P: = 0.01 in the right eye, P: = 0.02 in the left eye).
Thirty-eight percent of the dexamethasone group showed an increase in IOP to more
than 21 mmHg during the four postoperative weeks. No increase in IOP was noted in
the diclofenac group. CONCLUSIONS: Topical diclofenac is superior to
dexamethasone for each of the five postoperative parameters examined. Its maximal
effect occurred at 2 weeks after surgery, without an increase in IOP or in local
subconjunctival hemorrhage.
PMID- 11013194
TI - Comparison of artificial eye amplitudes with acrylic and hydroxyapatite spherical
enucleation implants.
AB - PURPOSE: To compare artificial eye amplitudes in patients who randomly received
either a hydroxyapatite or an acrylic, scleral-covered spherical implant after
enucleation. DESIGN: Randomized, controlled trial. PARTICIPANTS: Thirty-four
consecutive patients who underwent enucleation because of an intraocular melanoma
and 21 healthy control participants from the hospital staff. METHODS: Eligible
patients randomly received a hydroxyapatite or an acrylic, scleral-covered
spherical orbital implant. Fourteen patients were fitted with a hydroxyapatite
implant, and 16 were fitted with an acrylic implant. We measured horizontal and
vertical saccadic amplitudes of both the artificial eye and the healthy eye.
Measurements were performed with the magnetic search coils technique. Saccadic
amplitudes of the artificial eye were compared with the healthy eye of the
patient. The amplitudes of the healthy eyes were compared with saccadic
amplitudes of control participants. The interval from surgery to measurements was
at least 3 months in all patients. Saccadic gain (artificial eye and eye
amplitude divided by target amplitude) and saccadic symmetry (artificial eye
amplitude divided by healthy eye amplitude) were calculated. MAIN OUTCOME
MEASURES: Saccadic gain and saccadic symmetry. RESULTS: The gain in the healthy
eyes of the patients was comparable with the gain of the control eyes. Saccadic
symmetry was 1.0 in control participants. In patients, it was 0.334 in horizontal
saccades and 0.577 in vertical saccades. However, saccadic symmetry did not
differ significantly between the acrylic group and the hydroxyapatite group (P: >
0.1 for any saccadic direction). Equivalence was detectable with a power more
than 90% for horizontal saccades and more than 80% for vertical saccades.
Curvilinearity was rejected for both patient groups and for all saccadic
directions (P: > 0.5). CONCLUSIONS: When no motility peg is placed, acrylic and
hydroxyapatite spherical implants yield comparable saccadic amplitudes of the
artificial eye. Artificial eye amplitudes were markedly more restricted
horizontally than vertically. In all saccadic directions, the relation between
target amplitude and artificial eye amplitude was linear.
PMID- 11013195
TI - Eyelid abnormalities in lamellar ichthyoses.
AB - PURPOSE: To describe eyelid abnormalities in lamellar ichthyoses (LI). DESIGN:
Retrospective observational case series. PARTICIPANTS: Eight patients with
classic LI and two patients with congenital ichthyosiform erythroderma. METHODS:
Results of eyelid and corneal examinations of 10 patients with LI were reviewed
and analyzed with emphasis on the relationship between eyelid ectropion and
corneal damage. RESULTS: All patients presented with cicatricial lagophthalmos.
Of the eight patients with classic LI, five had ectropion of the four eyelids,
one had only lower ectropion, and two had no degree of ectropion. Two patients
with congenital ichthyosiform erythroderma had distinct eyelid abnormalities,
including madarosis and eyelash retraction. Loss of vision caused by corneal
damage was found in three patients with classic LI. Of these three patients, two
did not have upper eyelid ectropion. CONCLUSIONS: Severe corneal damage can occur
in LI even if there is no upper or lower eyelid ectropion.
PMID- 11013196
TI - Computed tomography in the diagnosis and prognosis of open-globe injuries.
AB - OBJECTIVE: Determine sensitivity, specificity, and prognostic signs of orbital
and ocular computed tomography (CT) in diagnosing patients with open globe
injury. DESIGN: Randomized masked review of computed tomograms and retrospective
clinical correlation of patients with ocular trauma. PARTICIPANTS: Two hundred
patients who underwent CT evaluation for ocular trauma between 1989 and 1993.
METHODS: CTs were read by three masked observers; findings were tabulated and
compared for variability among observers; sensitivity and specificity were
calculated and CT findings were grouped according to visual outcome retrieved
from record review. RESULTS: In the absence of clinical information, sensitivity
and specificity were 75% and 93%, respectively. The positive predictive value
ranged from 88% to 97%, with a calculated overall positive predictive value of
95%. Patients who had a poor visual outcome (visual acuity <2/200) or who
underwent enucleation had significantly more CT findings than patients with a
good visual outcome. Vitreous hemorrhage, absence of lens, and severe distortion
of vitreous space are among the most common CT findings associated with poor
visual outcome. CONCLUSIONS: CT is not sensitive enough to be solely relied upon
for diagnosis of all open globe injuries. CT findings only complement clinical
findings, increasing the clinician's overall ability to make an accurate
diagnosis of open globe injury, and may provide useful prognostic information
regarding visual outcome.
PMID- 11013197
TI - Pseudotumor cerebri and optic nerve sheath decompression.
AB - OBJECTIVE: To determine the efficacy and safety of optic nerve sheath
decompression in a large population of patients with pseudotumor cerebri with
visual loss despite medical treatment and to suggest a treatment algorithm on the
basis of these data. DESIGN: Retrospective, noncomparative, interventional case
series. PARTICIPANTS: One hundred fifty-eight eyes in 86 patients with
pseudotumor cerebri. INTERVENTION: Optic nerve sheath decompression. MAIN OUTCOME
MEASURES: Visual acuity, visual fields, and surgical complications. RESULTS:
After optic nerve sheath decompression for pseudotumor cerebri, visual acuity
stabilized or improved in 148 of 158 (94%) eyes, and visual fields stabilized or
improved in 71 of 81 (88%) eyes. Surgical complications, most of which were
transient and benign, were seen in 39 of 86 patients. Only one eye in one patient
had permanent severe visual loss secondary to an operative complication.
CONCLUSIONS: In patients with pseudotumor cerebri with progressive visual loss
despite maximum medical therapy, optic nerve sheath decompression is a safe and
effective means of stabilizing visual acuity and the visual fields of those
tested.
PMID- 11013199
TI - Discussion by H. Stanley thompson, MD
PMID- 11013198
TI - Portable pupillography of the swinging flashlight test to detect afferent
pupillary defects.
AB - OBJECTIVE: To investigate the ability of a portable, personal computer-driven,
pupillometer to record the pupillary response curve during the swinging
flashlight test. Also, to determine whether these response curves can be used to
identify and quantify relative asymmetry in the pupillary light reflex between
eyes in healthy volunteers with simulated afferent pupil defects (APDs) and
patients with optic neuropathies. DESIGN: Comparative, observational case series
and instrument validation. PARTICIPANTS: Healthy volunteers with no known ocular
disease and patients (n = 20) with various optic neuropathies noted to have
relative APDs on examination. METHODS: Pupillary response curves of the right eye
were recorded with a portable, electronic, infrared pupillometer from healthy
volunteers (with and without simulated APDs) and patients with APDs while the
light stimulus alternated between eyes, simulating the swinging flashlight test.
Simulated APDs in healthy volunteers were created with increasingly dense neutral
density filters in front of the left eye. MAIN OUTCOME MEASURES: Differences in
constriction amplitude, latency, and constriction velocity of the pupillary
response with right eye stimulation versus left eye stimulation in both groups of
subjects. RESULTS: A significant correlation between neutral density filter
strength and intereye differences was seen for all measurement parameters in
volunteers with simulated APDs. Depending on the measurement parameter and
stimulus intensity, simulated APDs of 0.6 log units or more could be
distinguished from normal responses. Clinically graded true APDs had intereye
differences similar to simulated APDs of the same density. Those with real and
simulated APDs of 0.9 log units or more could be distinguished from healthy
volunteers with 80% sensitivity and 92% specificity. Responses from those with
real and simulated small APDs of 0.3 to 0.6 log units could not be distinguished
reliably. CONCLUSIONS: Portable, personal-computer driven, electronic, infrared
pupillography can record the swinging flashlight test accurately and identify
large afferent pupillary defects. An affordable, portable, reliable device for
identifying relative APDs would be useful in the identification and follow-up of
patients with neurogenic vision loss.
PMID- 11013200
TI - Primary scleral buckling in open-globe injury involving the posterior segment.
AB - PURPOSE: To determine whether scleral buckle placement at the time of primary
repair of open-globe injury of the posterior segment is beneficial. DESIGN:
Retrospective, comparative, nonrandomized interventional study. PARTICIPANTS: One
hundred twenty-five open-globe injuries treated at the Duke University Medical
Center from June 1980 to May 1997. METHODS: Open-globe injuries were classified
with the Open-globe Injury Classification. Eyes that had zone 2 and 3 injuries
that had a primary buckle placed were compared with those that did not. MAIN
OUTCOME MEASURES: Subsequent retinal detachment, visual outcome, and need for
subsequent scleral buckling. RESULTS: The rate of retinal detachment and the
visual outcome were similar in the two groups. More than half of those who did
not have a primary buckle placed had subsequent scleral buckling surgery.
CONCLUSIONS: Many open-globe injuries of the posterior segment require eventual
scleral buckle. There may be a role for placement of a scleral buckle at the time
of primary repair.
PMID- 11013201
TI - Radioactive plaque therapy for metastatic choroidal carcinoma.
AB - PURPOSE: To describe the outcome of radioactive episcleral plaque therapy for
treatment of metastatic carcinoma to the choroid. DESIGN: Retrospective,
noncomparative case series. PARTICIPANTS: Five patients (six eyes) with carcinoma
metastatic to the choroid. METHODS: Retrospective review of the clinical records
of five patients (six eyes) who underwent radioactive episcleral plaque therapy
for choroidal metastases. MAIN OUTCOME MEASURES: Tumor height, visual acuity,
radiation optic neuropathy, and radiation retinopathy. RESULTS: Radioactive
episcleral plaque therapy resulted in shrinkage of the treated tumors and
resolution of subretinal fluid in all eyes. After plaque treatment, best
corrected visual acuity was maintained within two lines of initial visual acuity
for two eyes, decreased more than two lines for one eye, and improved more than
two lines in three eyes. The treatment was well tolerated and there was no acute
toxicity. Late complications included optic nerve atrophy (at 2 years) with
proliferative radiation retinopathy (at 3 years) in one eye and optic atrophy (at
6 months) in another eye that had received prior external beam therapy.
CONCLUSIONS: In carefully selected cases, radioactive episcleral plaque therapy
appears to be an effective and reasonable treatment for carcinoma metastatic to
the choroid.
PMID- 11013202
TI - Dexamethasone concentration in the subretinal fluid after a subconjunctival
injection, a peribulbar injection, or an oral dose.
AB - PURPOSE: To determine dexamethasone concentrations in the subretinal fluid of
patients after a peribulbar injection, a subconjunctival injection, or an oral
dose of dexamethasone and to compare the results with those of previous similar
studies of dexamethasone concentrations in the vitreous. DESIGN: Prospective,
nonrandomized, comparative trial. PARTICIPANTS: One hundred forty-eight patients
with a rhegmatogenous retinal detachment. METHODS: Fifty patients received a
peribulbar injection of 5 mg dexamethasone disodium phosphate, 49 received a
subconjunctival injection of 2.5 mg dexamethasone disodium phosphate, and 49
received an oral dose of 7. 5 mg dexamethasone at various time intervals before
surgery. At the time of surgery, a subretinal fluid sample was taken from each
patient. MAIN OUTCOME MEASURES: The dexamethasone concentration in the subretinal
fluid measured by radioimmunoassay. RESULTS: The estimated maximum dexamethasone
concentrations in the subretinal fluid after the peribulbar injection, the
subconjunctival injection, and the oral dose were, respectively, 82.2 ng/ml
(standard error, 17. 6), 359 ng/ml (standard error, 80.2), and 12.3 ng/ml
(standard error, 1.61). Corrected for dose, the maximum dexamethasone
concentrations after subconjunctival injection and peribulbar injection were,
respectively, 120 (95% confidence interval, 54/180) and 13 (95% confidence
interval, 6.8/20) times greater than after oral administration. CONCLUSIONS: A
subconjunctival injection of dexamethasone disodium phosphate is more effective
in delivering dexamethasone into the subretinal fluid of patients with a
rhegmatogenous retinal detachment compared with peribulbar injection or oral
administration. The subretinal dexamethasone concentrations were higher than
concentrations measured in the vitreous in previous studies with a similar setup
after all three delivery methods.
PMID- 11013204
TI - Discussion by raymond R. Margherio, MD
PMID- 11013203
TI - Macular hole surgery with and without internal limiting membrane peeling.
AB - OBJECTIVE: To compare results of surgery for idiopathic macular hole with and
without internal limiting membrane (ILM) peeling in a series of consecutive
patients over a 5-year period. DESIGN: A retrospective, nonrandomized,
comparative trial with concurrent control group. PARTICIPANTS: Forty-four eyes
with macular holes of less than or equal to 6 months duration without ILM peeling
were compared to 116 eyes with ILM peeling and the same hole duration. A third
group of 65 eyes with ILM peeling and duration greater than 6 months was also
evaluated. INTERVENTION: All eyes underwent pars plana vitrectomy with or without
ILM peeling, intravitreous gas, and positioning face down. No adjunctive
therapies were used in any group. MAIN OUTCOME MEASURES: Comparing the closure
and/or reopening rate, prognosis, visual acuity, and complications for macular
holes with and without ILM peeling. RESULTS: All patients had postsurgical follow
up of 18 months or greater. Primary closure was significantly improved with ILM
peeling with 116 of 116 eyes (100%) showing no reopenings versus 36 of 44 holes
(82%) primarily closed, 9 of which (25%) reopened without ILM peeling (P: <
0.00001) in holes less than or equal to 6 months. The 27 eyes without ILM peeling
that had successful surgery displayed a mean postoperative vision of 20/40, which
is the same as the successful eyes with ILM peeling (P: = 0.6). The 52 stage II
eyes with ILM peeling had a mean postoperative vision of 20/30, and 48 of the 52
eyes (92%) were 20/40 or better. Stage III eyes (greater than 400-microm holes)
without ILM peeling had a poor prognosis, with 6 of the 25 eyes (24%) having
initial surgery fail and an additional 4 of 25 eyes (16%) reopening. Without ILM
peeling, holes less than 300 microm had only one reopen, whereas holes greater
than or equal to 300 microm had 16 of the 17 (94%) primary failures and/or
reopenings (P: < 0.001). All 12 holes that reopened and/or primarily failed were
repaired with ILM peeling with excellent visual recovery. Macular holes with a
duration greater than 6 months were treated with ILM peeling, and 63 of 65 holes
(97%) were closed primarily and 65% had an increase in vision by two or more
Snellen lines. CONCLUSIONS: ILM peeling significantly improves visual and
anatomic success in all stages of recent and chronic macular holes and reopened
and failed holes, while eliminating reopening for holes greater than 300 microm.
PMID- 11013205
TI - Effect of stimulus size on static visual fields in patients with retinitis
pigmentosa.
AB - PURPOSE: To determine the effect of stimulus size on sensitivity of patients with
retinitis pigmentosa (RP) as measured by automated static perimetry. DESIGN:
Comparative case series. PARTICIPANTS: Thirty-nine patients with RP and a control
group of 10 healthy volunteers. METHODS: Automated static perimetry (full
threshold programs 24-2 or 30-2) was performed twice on one eye of each
participant using stimulus sizes III (0.43 degrees diameter) and V (1.72 degrees
diameter). Data from the same 50 test locations were used from each field. MAIN
OUTCOME MEASURES: At each location, for each participant, the size effect was
computed as the difference (in decibels) in sensitivities for sizes V and III,
and the average sensitivity was computed as the mean of sensitivities for the two
sizes. RESULTS: For both patient and control groups, the size effect was
negatively correlated with average sensitivity (r(2) > 0.124; P: < 0.001). The
mean size effect was significantly greater for the patient group than for the
control group: 8.6 (+/- 3.6) dB versus 5. 4 (+/- 2.2) dB (t = 18.0; P: < 0.001).
The percentage of abnormal locations (more than 8 dB below mean normal) tended to
be lower for size V than for size III, with a mean of 67% for size V versus 95%
for size III. The percentage of absolute defects was also lower for size V than
for size III, with a mean of 35% for size V versus 54% for size III. CONCLUSIONS:
In damaged regions of the visual fields of patients with RP, increase in stimulus
size from III to V can produce abnormally large increases in perimetric
sensitivity. Size III may be more useful than size V for detection of field
abnormality, whereas size V may be more useful than size III for observing
progression of advanced RP.
PMID- 11013206
TI - Ocular-central nervous system lymphoma mimicking posterior scleritis with
exudative retinal detachment.
AB - OBJECTIVE: We describe an unusual ocular presentation of ocular-central nervous
system lymphoma in a young patient. DESIGN: Interventional case report and
literature review. METHODS: A previously well 24-year-old white woman presented
with left eye pain and reduced vision. Episcleral injection, globe tenderness, an
afferent pupil defect, and exudative retinal detachment were present. Computed
tomographic scan of the head and orbits demonstrated scleral thickening, retinal
detachment, and no other abnormality. A provisional diagnosis of posterior
scleritis with exudative retinal detachment was made. Investigation for
underlying connective tissue diseases was negative. There was an initial prompt
response to corticosteroid therapy. The patient's symptoms and signs then
recurred, and a left third cranial nerve palsy developed. Systemic investigations
including lumbar puncture ultimately led to the diagnosis of primary T-cell
central nervous system (CNS) lymphoma. Serologic tests for human immunodeficiency
virus were negative. MAIN OUTCOME MEASURES AND RESULTS: The patient underwent
orbital and cranial irradiation and intrathecal and systemic chemotherapy.
Despite an initial response to treatment, she returned with a recurrence of the
lymphoma in the anterior segment of the left eye. Her systemic disease progressed
rapidly, and she died shortly thereafter. CONCLUSIONS: This patient's young age
and initial presentation mimicking posterior scleritis with unilateral exudative
retinal detachment, without evidence of vitreous involvement, are highly unusual
for ocular involvement in primary CNS lymphoma. A review of the literature
highlights the atypical nature of this presentation.
PMID- 11013207
TI - Differential electron flow around photosystem I by two C(4)-photosynthetic-cell
specific ferredoxins.
AB - In the C(4) plant maize (Zea mays L.), two ferredoxin isoproteins, Fd I and Fd
II, are expressed specifically in mesophyll and bundle-sheath cells,
respectively. cDNAs for these ferredoxins were introduced separately into the
cyanobacterium Plectonema boryanum with a disrupted endogenous ferredoxin gene,
yielding TM202 and KM2-9 strains expressing Fd I and Fd II. The growth of TM202
was retarded under high light (130 micromol/m(2)/s), whereas KM2-9 grew at a
normal rate but exhibited a nitrogen-deficient phenotype. Measurement of
photosynthetic O(2) evolution revealed that the reducing power was not
efficiently partitioned into nitrogen assimilation in KM2-9. After starvation of
the cells in darkness, the P700 oxidation level under far-red illumination
increased significantly in TM202. However, it remained low in KM2-9, indicating
an active cyclic electron flow. In accordance with this, the cellular ratio of
ATP/ADP increased and that of NADPH/NADP(+) decreased in KM2-9 as compared with
TM202. These results demonstrated that the two cell type-specific ferredoxins
differentially modulate electron flow around photosystem I.
PMID- 11013208
TI - A short sequence in the N-terminal region is required for the trimerization of
type XIII collagen and is conserved in other collagenous transmembrane proteins.
AB - The recombinant transmembrane protein type XIII collagen is shown to reside on
the plasma membrane of insect cells in a 'type II' orientation. Expressions of
deletion constructs showed that sequences important for the association of three
alpha1(XIII) chains reside in their N- rather than C-terminal portion. In
particular, a deletion of residues 63-83 immediately adjacent to the
transmembrane domain abolished the formation of disulfide-bonded trimers. The
results imply that nucleation of the type XIII collagen triple helix occurs at
the N-terminal region and that triple helix formation proceeds from the N- to the
C-terminus, in opposite orientation to that of the fibrillar collagens.
Interestingly, a sequence homologous to the deleted residues was found at the
same plasma membrane-adjacent location in other collagenous transmembrane
proteins, suggesting that it may be a conserved association domain. The type XIII
collagen was secreted into insect cell medium in low amounts, but this secretion
was markedly enhanced when the cytosolic portion was lacking. The cleavage
occurred in the non-collagenous NC1 domain after four arginines and was inhibited
by a furin protease inhibitor.
PMID- 11013209
TI - Targeted deletion of keratins 18 and 19 leads to trophoblast fragility and early
embryonic lethality.
AB - It has been reported previously that keratin 8 (K8)-deficient mice of one strain
die from a liver defect at around E12.5, while those of another strain suffer
from colorectal hyperplasia. These findings have generated considerable confusion
about the function of K8, K18 and K19 that are co-expressed in the mouse
blastocyst and internal epithelia. To resolve this issue, we produced mice doubly
deficient for K18 and K19 leading to complete loss of keratin filaments in early
mouse development. These embryos died at around day E9.5 with 100% penetrance.
The absence of keratins caused cytolysis restricted to trophoblast giant cells,
followed by haematomas in the trophoblast layer. Up to that stage, embryonic
development proceeded unaffected in the absence of keratin filaments. K18/19
deficient mouse embryos die earlier than any other intermediate filament
knockouts reported so far, suggesting that keratins, in analogy to their well
established role in epidermis, are essential for the integrity of a specialized
embryonic epithelium. Our data also offer a rationale to explore the involvement
of keratin mutations in early abortions during human pregnancies.
PMID- 11013211
TI - Membrane proteins organize a symmetrical virus.
AB - Alphaviruses are enveloped icosahedral viruses that mature by budding at the
plasma membrane. According to a prevailing model maturation is driven by binding
of membrane protein spikes to a preformed nucleocapsid (NC). The T = 4 geometry
of the membrane is thought to be imposed by the NC through one-to-one
interactions between spike protomers and capsid proteins (CPs). This model is
challenged here by a Semliki Forest virus capsid gene mutant. Its CPs cannot
assemble into NCs, or its intermediate structures, due to defective CP-CP
interactions. Nevertheless, it can use its horizontal spike-spike interactions on
membrane surface and vertical spike-CP interactions to make a particle with
correct geometry and protein stoichiometry. Thus, our results highlight the
direct role of membrane proteins in organizing the icosahedral conformation of
alphaviruses.
PMID- 11013210
TI - Transfer of palmitate from phospholipids to lipid A in outer membranes of gram
negative bacteria.
AB - Regulated covalent modifications of lipid A are implicated in virulence of
pathogenic Gram-negative bacteria. The Salmonella typhimurium PhoP/PhoQ-activated
gene pagP is required both for biosynthesis of hepta-acylated lipid A species
containing palmitate and for resistance to cationic anti-microbial peptides.
Palmitoylated lipid A can also function as an endotoxin antagonist. We now show
that pagP and its Escherichia coli homolog (crcA) encode an unusual enzyme of
lipid A biosynthesis localized in the outer membrane. PagP transfers a palmitate
residue from the sn-1 position of a phospholipid to the N-linked hydroxymyristate
on the proximal unit of lipid A (or its precursors). PagP bearing a C-terminal
His(6)-tag accumulated in outer membranes during overproduction, was purified
with full activity and was shown by cross-linking to behave as a homodimer. PagP
is the first example of an outer membrane enzyme involved in lipid A
biosynthesis. Additional pagP homologs are encoded in the genomes of Yersinia and
Bordetella species. PagP may provide an adaptive response toward both Mg(2+)
limitation and host innate immune defenses.
PMID- 11013212
TI - Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient
cells.
AB - The hexosamine pathway provides UDP-N:-acetylhexosamine donor substrates used in
cytosolic and Golgi-mediated glycosylation of proteins and for formation of
glycosylphosphatidylinositol (GPI) anchors, which tether proteins to the outer
plasma membrane. We have recently identified the murine glucosamine-6-phosphate
(GlcN6P) acetyltransferase, EMeg32, as a developmentally regulated enzyme on the
route to UDP-N:-acetylglucosamine (UDP-GlcNAc). Here we describe embryos and
cells that have the EMeg32 gene inactivated by homologous recombination.
Homozygous mutant embryos die at around embryonic day (E) 7.5 with a general
proliferative delay of development. In vitro differentiated EMeg32(-/-) ES cells
show reduced proliferation. Mouse embryonic fibroblasts (MEFs) deficient for
EMeg32 exhibit defects in proliferation and adhesiveness, which could be
complemented by stable re-expression of EMeg32 or by nutritional restoration of
intracellular UDP-GlcNAc levels. Reduced UDP-GlcNAc levels predominantly
translated into decreased O-GlcNAc modifications of cytosolic and nuclear
proteins. Interestingly, growth-impaired EMeg32(-/-) MEFs withstand a number of
apoptotic stimuli and express activated PKB/AKT. Thus, EMeg32-dependent UDP
GlcNAc levels influence cell cycle progression and susceptibility to apoptotic
stimuli.
PMID- 11013213
TI - Crystal structure of the GAP domain of Gyp1p: first insights into interaction
with Ypt/Rab proteins.
AB - We present the 1.9 A resolution crystal structure of the catalytic domain of
Gyp1p, a specific GTPase activating protein (GAP) for Ypt proteins, the yeast
homologues of Rab proteins, which are involved in vesicular transport. Gyp1p is a
member of a large family of eukaryotic proteins with shared sequence motifs.
Previously, no structural information was available for any member of this class
of proteins. The GAP domain of Gyp1p was found to be fully alpha-helical.
However, the observed fold does not superimpose with other alpha-helical GAPs
(e.g. Ras- and Cdc42/Rho-GAP). The conserved and catalytically crucial arginine
residue, identified by mutational analysis, is in a comparable position to the
arginine finger in the Ras- and Cdc42-GAPs, suggesting that Gyp1p utilizes an
arginine finger in the GAP reaction, in analogy to Ras- and Cdc42-GAPs. A model
for the interaction between Gyp1p and the Ypt protein satisfying biochemical data
is given.
PMID- 11013214
TI - p56(dok-2) as a cytokine-inducible inhibitor of cell proliferation and signal
transduction.
AB - p56(dok-2) acts as a multiple docking protein downstream of receptor or non
receptor tyrosine kinases. However, the role of p56(dok-2) in biological
functions of cells is not clear. We found that transcription of the p56(dok-2)
gene in macrophages was increased markedly in response to cytokines such as
macrophage colony-stimulating factor (M-CSF), granulocyte/macrophage-CSF and
interleukin-3 (IL-3). Forced expression of p56(dok-2) inhibited M-CSF-,
granulocyte-CSF-, IL-3- and stem cell factor-induced proliferation of myeloid
leukemia cells, M-NFS-60. The p56(dok-2)-overexpressing cells showed an impaired
induction of c-myc but not of c-jun, junB or c-fos when stimulated with M-CSF.
Consistent with these results, the peritoneal cavity of the hairless (hr/hr)
strain of mutant mice, whose cells expressed less p56(dok-2) than wild-type mice,
contained more macrophages than that of +/hr mice. Moreover, the inhibition of
endogenous p56(dok-2) expression in macrophage-like tumor cells, J774A.1, by
stable expression of antisense p56(dok-2) mRNA accelerated cell proliferation.
The study identifies a novel role for p56(dok-2) as a molecule that negatively
regulates signal transduction and cell proliferation mediated by cytokines in a
feedback loop.
PMID- 11013215
TI - CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T
lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway.
AB - CD95 (APO-1/Fas) is a member of the tumor necrosis factor receptor family, which
can trigger apoptosis in a variety of cell types. However, little is known of the
mechanisms underlying cell susceptibility to CD95-mediated apoptosis. Here we
show that human T cells that are susceptible to CD95-mediated apoptosis, exhibit
a constitutive polarized morphology, and that CD95 colocalizes with ezrin at the
site of cellular polarization. In fact, CD95 co-immunoprecipitates with ezrin
exclusively in lymphoblastoid CD4(+) T cells and primary long-term activated T
lymphocytes, which are prone to CD95-mediated apoptosis, but not in short-term
activated T lymphocytes, which are refractory to the same stimuli, even
expressing equal levels of CD95 on the cell membrane. Pre-treatment with ezrin
antisense oligonucleotides specifically protected from the CD95-mediated
apoptosis. Moreover, we show that the actin cytoskeleton integrity is essential
for this function. These findings strongly suggest that the CD95 cell membrane
polarization, through an ezrin-mediated association with the actin cytoskeleton,
is a key intracellular mechanism in rendering human T lymphocytes susceptible to
the CD95-mediated apoptosis.
PMID- 11013216
TI - MDM2 induces hyperplasia and premalignant lesions when expressed in the basal
layer of the epidermis.
AB - The MDM2 oncogene is overexpressed in 5-10% of human tumours. Its major
physiological role is to inhibit the tumour suppressor p53. However, MDM2 has p53
independent effects on differentiation and does not predispose to tumorigenesis
when it is expressed in the granular layer of the epidermis. These unexpected
properties of MDM2 could be tissue specific or could depend on the
differentiation state of the cells. Strikingly, we found that MDM2 has p53
dependent effects on differentiation, proliferation and apoptosis when it is
expressed in the less differentiated basal layer cells. MDM2 inhibits UV
induction of p53, the cell cycle inhibitor p21(WAF1/CIP1) and apoptosis ('sunburn
cells'). Importantly, MDM2 increases papilloma formation induced by chemical
carcinogenesis and predisposes to the appearance of premalignant lesions and
squamous cell carcinomas. p53 has a natural role in the protection against UV
damage in the basal layer of the epidermis. Our results show that MDM2
predisposes to tumorigenesis when expressed at an early stage of differentiation,
and provide a mouse model of MDM2 tumorigenesis relevant to p53's tumour
suppressor functions.
PMID- 11013217
TI - A Caenorhabditis elegans MAP kinase kinase, MEK-1, is involved in stress
responses.
AB - The c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein
kinase (MAPK) family, was shown to be involved in the response to various
stresses in cultured cells. However, there is little in vivo evidence indicating
a role for a JNK pathway in the stress response of an organism. We identified the
Caenorhabditis elegans mek-1 gene, which encodes a 347 amino acid protein highly
homologous to mammalian MKK7, an activator of JNK. Mek-1 reporter fusion proteins
are expressed in pharyngeal muscle, uterus, a portion of intestine, and neurons.
A mek-1 deletion mutant is hypersensitive to copper and cadmium ions and to
starvation. A wild-type mek-1 transgene rescued the hypersensitivity to the metal
ions. Double mutants of mek-1 with an eat-5, eat-11 or eat-18 mutation, which are
characterized by a limited feeding defect, showed distinct growth defects under
normal conditions. Expression of an activated form of MEK-1 in the whole animal
or specifically in the pharynx inhibited pharyngeal pumping. These results
suggest a role for mek-1 in stress responses, with a focus in the pharynx and/or
intestine.
PMID- 11013218
TI - H2O2 sensing through oxidation of the Yap1 transcription factor.
AB - The yeast transcription factor Yap1 activates expression of antioxidant genes in
response to oxidative stress. Yap1 regulation involves nuclear accumulation, but
the mechanism sensing the oxidative stress signal remains unknown. We provide
biochemical and genetic evidence that upon H2O2 treatment, Yap1 is activated by
oxidation and deactivated by enzymatic reduction with Yap1-controlled
thioredoxins, thus providing a mechanism for autoregulation. Two cysteines
essential for Yap1 oxidation are also essential for its activation by H2O2. The
data are consistent with a model in which oxidation of Yap1 leads to disulfide
bond formation with the resulting change of conformation masking recognition of
the nuclear export signal by Crm1/Xpo1, thereby promoting nuclear accumulation of
the protein. In sharp contrast to H2O2, diamide does not lead to the same Yap1
oxidized form and still activates mutants lacking cysteines essential for H2O2
activation, providing a molecular basis for differential activation of Yap1 by
these oxidants. This is the first example of an H2O2-sensing mechanism in a
eukaryote that exploits the oxidation of cysteines in order to respond rapidly to
stress conditions.
PMID- 11013219
TI - Crystal structure of FadR, a fatty acid-responsive transcription factor with a
novel acyl coenzyme A-binding fold.
AB - FadR is a dimeric acyl coenzyme A (acyl CoA)-binding protein and transcription
factor that regulates the expression of genes encoding fatty acid biosynthetic
and degrading enzymes in Escherichia coli. Here, the 2.0 A crystal structure of
full-length FadR is described, determined using multi-wavelength anomalous
dispersion. The structure reveals a dimer and a two-domain fold, with DNA-binding
and acyl-CoA-binding sites located in an N-terminal and C-terminal domain,
respectively. The N-terminal domain contains a winged helix-turn-helix
prokaryotic DNA-binding fold. Comparison with known structures and analysis of
mutagenesis data delineated the site of interaction with DNA. The C-terminal
domain has a novel fold, consisting of a seven-helical bundle with a crossover
topology. Careful analysis of the structure, together with mutational and
biophysical data, revealed a putative hydrophobic acyl-CoA-binding site, buried
in the core of the seven-helical bundle. This structure aids in understanding
FadR function at a molecular level, provides the first structural scaffold for
the large GntR family of transcription factors, which are keys in the control of
metabolism in bacterial pathogens, and could thus be a possible target for novel
chemotherapeutic agents.
PMID- 11013221
TI - Transcriptional silencing and promoter methylation triggered by double-stranded
RNA.
AB - Double-stranded RNA induces a post-transcriptional gene silencing process, termed
RNAi, in diverse organisms. It is shown here that transcriptional gene silencing
accompanied by de novo methylation of a target promoter in plants can be
triggered by a double-stranded RNA containing promoter sequences. Similar to the
double-stranded RNA involved in RNAi, this promoter double-stranded RNA, which is
synthesized in the nucleus, is partially cleaved into small RNAs approximately 23
nucleotides in length. Both transcriptional and post-transcriptional gene
silencing can thus be initiated by double-stranded RNAs that enter the same
degradation pathway. The results also implicate double-stranded RNA in directing
DNA methylation. Different constructs designed to produce double-stranded
promoter RNA in various ways were evaluated for their ability to induce gene
silencing in tobacco and Arabidopsis. RNA hairpins transcribed from inverted DNA
repeats were the most effective trans-acting silencing signals. This strategy
could be useful for transcriptionally downregulating genes in a variety of
plants.
PMID- 11013220
TI - Smad2, Smad3 and Smad4 cooperate with Sp1 to induce p15(Ink4B) transcription in
response to TGF-beta.
AB - Transforming growth factor-beta (TGF-beta) arrests growth of epithelial cells by
inducing the transcription of p15(Ink4B), a cyclin-dependent kinase inhibitor. In
this study, we demonstrate that p15(Ink4B) induction was mediated by a TGF-beta
induced complex of Smad2, Smad3, Smad4 and Sp1. Mutations in the Sp1- or Smad
binding sequences decreased or abolished the TGF-beta responsiveness of the
p15(Ink4B) promoter. Interference with, or deficiency in, Smad2, Smad3 or Smad4
functions also reduced or abolished the TGF-beta-dependent p15(Ink4B) induction,
whereas the absence of Sp1 reduced the basal and TGF-beta-induced p15(Ink4B)
transcription. In the nucleoprotein complex, Smad2 interacted through its C
domain with Sp1 and enhanced the DNA binding and transcriptional activity of Sp1.
Smad3 interacted indirectly with Sp1 through its association with Smad2 and/or
Smad4, and bound directly to the p15(Ink4B) promoter. Finally, Smad4 interacted
through its N-domain with Sp1. Our data demonstrate the physical interactions and
functional cooperativity of Sp1 with a complex of Smad2, Smad3 and Smad4 in the
induction of the p15(Ink4B) gene. These findings explain the tumor suppressor
roles of Smad2 and Smad4 in growth arrest signaling by TGF-beta.
PMID- 11013222
TI - Targeting the chromatin-remodeling MSL complex of Drosophila to its sites of
action on the X chromosome requires both acetyl transferase and ATPase
activities.
AB - Dosage compensation in Drosophila is mediated by a multiprotein, RNA-containing
complex that associates with the X chromosome at multiple sites. We have
investigated the role that the enzymatic activities of two complex components,
the histone acetyltransferase activity of MOF and the ATPase activity of MLE, may
have in the targeting and association of the complex with the X chromosome. Here
we report that MLE and MOF activities are necessary for complexes to access the
various X chromosome sites. The role that histone H4 acetylation plays in this
process is supported by our observations that MOF overexpression leads to the
ectopic association of the complex with autosomal sites.
PMID- 11013223
TI - Quorum-sensing signal binding results in dimerization of TraR and its release
from membranes into the cytoplasm.
AB - Promoter binding by TraR and LuxR, the activators of two bacterial quorum-sensing
systems, requires their cognate acyl-homoserine lactone (acyl-HSL) signals, but
the role the signal plays in activating these transcription factors is not known.
Soluble active TraR, when purified from cells grown with the acyl-HSL, contained
bound signal and was solely in dimer form. However, genetic and cross-linking
studies showed that TraR is almost exclusively in monomer form in cells grown
without signal. Adding signal resulted in dimerization of the protein in a
concentration-dependent manner. In the absence of signal, monomer TraR localized
to the inner membrane while growth with the acyl-HSL resulted in the appearance
of dimer TraR in the cytoplasmic compartment. Affinity chromatography indicated
that the N-terminus of TraR from cells grown without signal is hidden. Analysis
of heterodimers formed between TraR and its deletion mutants localized the
dimerization domain to a region between residues 49 and 156. We conclude that
binding signal drives dimerization of TraR and its release from membranes into
the cytoplasm.
PMID- 11013224
TI - Synergistic transcription activation: a dual role for CRP in the activation of an
Escherichia coli promoter depending on MalT and CRP.
AB - Activation of the Escherichia coli malEp promoter relies on the formation of a
higher order structure involving cooperative binding of MalT to promoter-proximal
and promoter-distal sites as well as CRP binding to three sites located in
between. MalT is the primary activator and one function of CRP is to facilitate
cooperative binding of MalT to its cognate sites by bending the intervening DNA.
It is shown here that CRP also participates directly in malEp activation. This
function is carried out by the molecule of CRP bound to the CRP site centered at
139.5 (CRP site 3). This molecule of CRP recruits RNA polymerase by promoting the
binding of the RNA polymerase alpha subunit C-terminal domain (alphaCTD) to DNA
immediately downstream from CRP site 3, via a contact between alphaCTD and
activating region I of CRP. The action of MalT and CRP at malEp hence provides
the example of a novel and complex mechanism for transcriptional synergy in
prokaryotes whereby one activator both helps the primary activator to form a
productive complex with promoter DNA and interacts directly with RNA polymerase
holoenzyme.
PMID- 11013225
TI - Mapping the fMet-tRNA(f)(Met) binding site of initiation factor IF2.
AB - The interaction between fMet-tRNA(f)(Met) and Bacillus stearothermophilus
translation initiation factor IF2 has been characterized. We demonstrate that
essentially all thermodynamic determinants governing the stability and the
specificity of this interaction are localized within the acceptor hexanucleotide
fMet-3'ACCAAC of the initiator tRNA and a fairly small area at the surface of the
beta-barrel structure of the 90-amino acid C-terminal domain of IF2 (IF2 C-2). A
weak but specific interaction between IF2 C-2 and formyl-methionyl was also
demonstrated. The surface of IF2 C-2 interacting with fMet-tRNA(f)(Met) has been
mapped using two independent approaches, site- directed mutagenesis and NMR
spectroscopy, which yielded consistent results. The binding site comprises C668
and G715 located in a groove accommodating the methionyl side-chain, R700, in the
vicinity of the formyl group, Y701 and K702 close to the acyl bond between fMet
and tRNA(f)(Met), and the surface lined with residues K702-S660, along which the
acceptor arm of the initiator tRNA spans in the direction 3' to 5'.
PMID- 11013226
TI - Ribosomal protein L2 is involved in the association of the ribosomal subunits,
tRNA binding to A and P sites and peptidyl transfer.
AB - Ribosomal proteins L2, L3 and L4, together with the 23S RNA, are the main
candidates for catalyzing peptide bond formation on the 50S subunit. That L2 is
evolutionarily highly conserved led us to perform a thorough functional analysis
with reconstituted 50S particles either lacking L2 or harboring a mutated L2. L2
does not play a dominant role in the assembly of the 50S subunit or in the
fixation of the 3'-ends of the tRNAs at the peptidyl-transferase center. However,
it is absolutely required for the association of 30S and 50S subunits and is
strongly involved in tRNA binding to both A and P sites, possibly at the elbow
region of the tRNAs. Furthermore, while the conserved histidyl residue 229 is
extremely important for peptidyl-transferase activity, it is apparently not
involved in other measured functions. None of the other mutagenized amino acids
(H14, D83, S177, D228, H231) showed this strong and exclusive participation in
peptide bond formation. These results are used to examine critically the proposed
direct involvement of His229 in catalysis of peptide synthesis.
PMID- 11013228
TI - Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase iota.
AB - Human DNA polymerase iota (pol(iota)) is a recently discovered enzyme that
exhibits extremely low fidelity on undamaged DNA templates. Here, we show that
poliota is able to facilitate limited translesion replication of a thymine
thymine cyclobutane pyrimidine dimer (CPD). More importantly, however, the bypass
event is highly erroneous. Gel kinetic assays reveal that pol(iota) misinserts T
or G opposite the 3' T of the CPD approximately 1.5 times more frequently than
the correct base, A. While pol(iota) is unable to extend the T.T mispair
significantly, the G.T mispair is extended and the lesion completely bypassed,
with the same efficiency as that of the correctly paired A. T base pair. By
comparison, pol(iota) readily misinserts two bases opposite a 6-4 thymine-thymine
pyrimidine-pyrimidone photoproduct (6-4PP), but complete lesion bypass is only a
fraction of that observed with the CPD. Our data indicate, therefore, that
poliota possesses the ability to insert nucleotides opposite UV photoproducts as
well as to perform unassisted translesion replication that is likely to be highly
mutagenic.
PMID- 11013227
TI - Subunit-specific degradation of the UmuD/D' heterodimer by the ClpXP protease:
the role of trans recognition in UmuD' stability.
AB - The Escherichia coli UmuD' protein is a subunit of the recently described error
prone DNA polymerase, pol V. UmuD' is initially synthesized as an unstable and
mutagenically inactive pro-protein, UmuD. Upon processing, UmuD' assumes a
relatively stable conformation and becomes mutagenically active. While UmuD and
UmuD' by themselves exist in vivo as homodimers, when together they
preferentially interact to form heterodimers. Quite strikingly, it is in this
context that UmuD' becomes susceptible to ClpXP-mediated proteolysis. Here we
report a novel targeting mechanism designed for degrading the mutagenically
active UmuD' subunit of the UmuD/D' heterodimer complex, while leaving the UmuD
protein intact. Surprisingly, a signal that is essential and sufficient for
targeting UmuD' for degradation was found to reside on UmuD not UmuD'. UmuD was
also shown to be capable of channeling an excess of UmuD' to ClpXP for
degradation, thereby providing a mechanism whereby cells can limit error-prone
DNA replication.
PMID- 11013229
TI - Pituitary tumor transforming gene causes aneuploidy and p53-dependent and p53
independent apoptosis.
AB - The pituitary tumor transforming gene, PTTG, is abundantly expressed in several
neoplasms. We recently showed that PTTG overexpression is associated with
apoptosis and therefore have now studied the role of p53 in this process. In MCF
7 breast cancer cells that express wild type p53, PTTG overexpression caused
apoptosis. p53 was translocated to the nuclei in cells expressing PTTG.
Overexpression of p53, along with PTTG, augmented apoptosis, whereas expression
of the human papillomavirus E6 protein inhibited PTTG-induced apoptosis. In MG-63
osteosarcoma cells that are deficient in p53, PTTG caused cell cycle arrest and
subsequent apoptosis that was inhibited by caspase inhibitors. A proteasome
inhibitor augmented PTTG expression in stable PTTG transfectants, suggesting that
down-regulated PTTG expression is required for cell survival. Finally, MG-63
cells expressing PTTG showed signs of aneuploidy including the presence of
micronuclei and multiple nuclei. These results indicate that PTTG overexpression
causes p53-dependent and p53-independent apoptosis. In the absence of p53, PTTG
causes aneuploidy. These results may provide a mechanism for PTTG-induced
tumorigenesis whereby PTTG mediates aneuploidy and subsequent cell
transformation.
PMID- 11013230
TI - Direct binding of activated c-Src to the beta 3-adrenergic receptor is required
for MAP kinase activation.
AB - Both beta(2)- and beta(3)-adrenergic receptors (ARs) are able to activate the
extracellular signal-regulated kinase (ERK) pathway. We previously showed that c
Src is required for ERK activation by beta(2)AR and that it is recruited to
activated beta(2)AR through binding of the Src homology 3 (SH3) domain to proline
rich regions of the adapter protein beta-arrestin1. Despite the absence of sites
for phosphorylation and beta-arrestin binding, ERK activation by beta(3)AR still
requires c-Src. Agonist activation of beta(2)AR, but not beta(3)AR, led to
redistribution of green fluorescent protein-tagged beta-arrestin to the plasma
membrane. In beta-arrestin-deficient COS-7 cells, beta-agonist-dependent co
precipitation of c-Src with the beta(2)AR required exogenous beta-arrestin, but
activated beta(3)AR co-precipitated c-Src in the absence or presence of beta
arrestin. ERK activation and Src co-precipitation with beta(3)AR also occurred in
adipocytes in an agonist-dependent and pertussis toxin-sensitive manner. Protein
interaction studies show that the beta(3)AR interacts directly with the SH3
domain of Src through proline-rich motifs (PXXP) in the third intracellular loop
and the carboxyl terminus. ERK activation and Src co-precipitation were abolished
in cells expressing point mutations in these PXXP motifs. Together, these data
describe a novel mechanism of ERK activation by a G protein-coupled receptor in
which the intracellular domains directly recruit c-Src.
PMID- 11013231
TI - Cell wall assembly by Pneumocystis carinii. Evidence for a unique gsc-1 subunit
mediating beta -1,3-glucan deposition.
AB - Pneumocystis carinii remains a persistent cause of severe pneumonia in immune
compromised patients. Recent studies indicate that P. carinii is a fungal species
possessing a glucan-rich cyst wall. Pneumocandin antagonists of beta-1,3-glucan
synthesis rapidly suppress infection in animal models of P. carinii pneumonia.
We, therefore, sought to define the molecular mechanisms of beta-glucan cell wall
assembly by P. carinii. Membrane extracts derived from freshly purified P.
carinii incorporate uridine 5'-diphosphoglucose into insoluble carbohydrate, in a
manner that was completely inhibited by the pneumocandin L733-560, an antagonist
of Gsc-1-type beta-glucan synthetases. Using degenerative polymerase chain
reaction and library screening, the P. carinii Gsc-1 catalytic subunit of beta
1,3-glucan synthetase was cloned and characterized. P. carinii gsc1 exhibited
homology to phylogenetically related fungal beta-1,3-glucan synthetases, encoding
a predicted 214-kDa integral membrane protein with 12 transmembrane domain
structure. Immunoprecipitation of P. carinii extracts, with a synthetic peptide
anti-Gsc-1 antibody, specifically yielded a protein of 219.4 kDa, which was also
capable of incorporating 5'-diphosphoglucose into insoluble glucan carbohydrate.
As opposed to other fungi, the expression of gsc-1 mRNA is uniquely regulated
over P. carinii's life cycle, having minimal expression in trophic forms, but
substantial expression in the thick-walled cystic form of the organism. These
results indicate that P. carinii contains a unique catalytic subunit of beta-1,3
glucan synthetase utilized in cyst wall formation. Because synthesis of beta-1,3
glucan is absent in mammalian cells, inhibition of the P. carinii Gsc-1
represents an attractive molecular target for therapeutic exploitation.
PMID- 11013232
TI - Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein
kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A
property common to most cyclin-dependent kinase inhibitors?
AB - The bis-indole indirubin is an active ingredient of Danggui Longhui Wan, a
traditional Chinese medicine recipe used in the treatment of chronic diseases
such as leukemias. The antitumoral properties of indirubin appear to correlate
with their antimitotic effects. Indirubins were recently described as potent
(IC(50): 50-100 nm) inhibitors of cyclin-dependent kinases (CDKs). We report here
that indirubins are also powerful inhibitors (IC(50): 5-50 nm) of an
evolutionarily related kinase, glycogen synthase kinase-3beta (GSK-3 beta).
Testing of a series of indoles and bis-indoles against GSK-3 beta, CDK1/cyclin B,
and CDK5/p25 shows that only indirubins inhibit these kinases. The structure
activity relationship study also suggests that indirubins bind to GSK-3 beta's
ATP binding pocket in a way similar to their binding to CDKs, the details of
which were recently revealed by crystallographic analysis. GSK-3 beta, along with
CDK5, is responsible for most of the abnormal hyperphosphorylation of the
microtubule-binding protein tau observed in Alzheimer's disease. Indirubin-3'
monoxime inhibits tau phosphorylation in vitro and in vivo at Alzheimer's disease
specific sites. Indirubins may thus have important implications in the study and
treatment of neurodegenerative disorders. Indirubin-3'-monoxime also inhibits the
in vivo phosphorylation of DARPP-32 by CDK5 on Thr-75, thereby mimicking one of
the effects of dopamine in the striatum. Finally, we show that many, but not all,
reported CDK inhibitors are powerful inhibitors of GSK-3 beta. To which extent
these GSK-3 beta effects of CDK inhibitors actually contribute to their
antimitotic and antitumoral properties remains to be determined. Indirubins
constitute the first family of low nanomolar inhibitors of GSK-3 beta to be
described.
PMID- 11013233
TI - Small maf (MafG and MafK) proteins negatively regulate antioxidant response
element-mediated expression and antioxidant induction of the NAD(P)H:Quinone
oxidoreductase1 gene.
AB - The antioxidant response element (ARE) is known to regulate expression and
induction of NQO1, GST Ya, and other detoxifying enzyme genes in response to
antioxidants and xenobiotics. The nuclear transcription factor Nrf2 and Nrf1 bind
to the ARE and positively regulate expression and induction of the NQO1 and GST
Ya genes. In this study, we demonstrate that overexpression of small Maf (MafG
and MafK) proteins negatively regulate ARE-mediated expression and tert-butyl
hydroquinone induction of the NQO1 and GST Ya genes in transfected Hep-G2 cells.
In similar experiments, overexpression of small Maf proteins also repressed Nrf2
mediated up-regulation of ARE-mediated NQO1 and GST Ya genes expression in Hep-G2
cells co-transfected with Nrf2 and small Maf proteins. Band and supershift assays
with the NQO1 gene ARE and nuclear proteins demonstrate that small MafG and MafK
bind to the ARE as Maf-Maf homodimers and Maf-Nrf2 heterodimers. Therefore, Maf
Maf homodimers and possibly Maf-Nrf2 heterodimers play a role in negative
regulation of ARE-mediated transcription and antioxidant induction of NQO1 and
other detoxifying enzyme genes. In contrast to Maf-Nrf2, the Maf-Nrf1
heterodimers failed to bind with the NQO1 gene ARE and did not demonstrate the
repressive effect in transfection assays.
PMID- 11013234
TI - Identification in Saccharomyces cerevisiae of two isoforms of a novel
mitochondrial transporter for 2-oxoadipate and 2-oxoglutarate.
AB - The nuclear genome of Saccharomyces cerevisiae encodes 35 members of a family of
membrane proteins. Known members transport substrates and products across the
inner membranes of mitochondria. We have localized two hitherto unidentified
family members, Odc1p and Odc2p, to the inner membranes of mitochondria. They are
isoforms with 61% sequence identity, and we have shown in reconstituted liposomes
that they transport the oxodicarboxylates 2-oxoadipate and 2-oxoglutarate by a
strict counter exchange mechanism. Intraliposomal adipate and glutarate and to a
lesser extent malate and citrate supported [14C]oxoglutarate uptake. The
expression of Odc1p, the more abundant isoform, made in the presence of
nonfermentable carbon sources, is repressed by glucose. The main physiological
roles of Odc1p and Odc2p are probably to supply 2-oxoadipate and 2-oxoglutarate
from the mitochondrial matrix to the cytosol where they are used in the
biosynthesis of lysine and glutamate, respectively, and in lysine catabolism.
PMID- 11013235
TI - Characterization of an upstream enhancer region in the promoter of the human
endothelial nitric-oxide synthase gene.
AB - The endothelial nitric-oxide synthase gene is constitutively expressed in
endothelial cells. Several transcriptionally active regulatory elements have been
identified in the proximal promoter, including a GATA-2 and an Sp-1 binding site.
Because they cannot account for the constitutive expression of endothelial nitric
oxide synthase gene in a restricted number of cells, we have searched for other
cell-specific regulatory elements. By DNase I hypersensitivity mapping and
deletion studies we have identified a 269-base pair activator element located 4.9
kilobases upstream from the transcription start site that acts as an enhancer.
DNase I footprinting and linker-scanning experiments showed that several regions
within the 269-base pair enhancer are important for transcription factor binding
and for full enhancer activity. The endothelial specificity of this activation
seems partly due to interaction between this enhancer in its native configuration
and the promoter in endothelial cells. EMSA experiments suggested the implication
of MZF-like, AP-2, Sp-1-related, and Ets-related factors. Among Ets factors, Erg
was the only one able to bind to cognate sites in the enhancer, as found by EMSA
and supershift experiments, and to activate the transcriptional activity of the
enhancer in cotransfection experiments. Therefore, multiple protein complexes
involving Erg, other Ets-related factors, AP-2, Sp-1-related factor, and MZF-like
factors are important for the function of this enhancer in endothelial cells.
PMID- 11013236
TI - Intron-exon swapping of transglutaminase mRNA and neuronal Tau aggregation in
Alzheimer's disease.
AB - In order to understand the mechanism for insoluble neurotoxic protein
polymerization in Alzheimer's disease (AD) brain neurons, we examined protein and
gene expression for transglutaminase (TGase 2; tissue transglutaminase (tTG)) in
hippocampus and isocortex. We found co-localization of tTG protein and activity
with tau-positive neurofibrillary tangles, whereas mRNA and sequence analysis
indicated an absolute increase in tTG synthesized. Although apoptosis in AD
hippocampus is now an established mode of neuronal cell death, no definite
underlying mechanism(s) is known. Since TGase-mediated protein aggregation is
implicated in polyglutamine ((CAG)(n)/Q(n) expansion) disorder apoptosis, and
expanded Q(n) repeats are excellent TGase substrates, a role for TGase in AD is
possible. However, despite such suggestions almost 20 years ago, the molecular
mechanism remained elusive. We now present one possible molecular mechanism for
tTG-mediated, neurotoxic protein polymerization leading to neuronal apoptosis in
AD that involves not its substrates (like Q(n) repeats) but rather the unique
presence of alternative transcripts of tTG mRNA. In addition to a full-length (L)
isoform in aged non-demented brains, we found a short isoform (S) lacking a
binding domain in all AD brains. Our current results identify intron-exon
"switching" between L and S isoforms, implicating G-protein-coupled signaling
pathways associated with tTG that may help to determine the dual roles of this
enzyme in neuronal life and death processes.
PMID- 11013237
TI - Regulation of glycogen synthesis by amino acids in cultured human muscle cells.
AB - Insulin and a number of metabolic factors stimulate glycogen synthesis and the
enzyme glycogen synthase. Using human muscle cells we find that glycogen
synthesis is stimulated by treatment of the cells with lithium ions, which
inhibit glycogen synthase kinase 3. Insulin further stimulates glycogen synthesis
in the presence of lithium ions, an effect abolished by wortmannin and rapamycin.
We report also that amino acids stimulate glycogen synthesis and glycogen
synthase, these effects also being blocked by rapamycin and wortmannin. Amino
acids stimulate p70(s6k) and transiently inhibit glycogen synthase kinase 3
without effects on the activity of protein kinase B or the mitogen-activated
protein kinase pathway. Thus, the work reported here demonstrates that amino acid
availability can regulate glycogen synthesis. Furthermore, it demonstrates that
glycogen synthase kinase 3 can be inactivated within cells independent of
activation of protein kinase B and p90(rsk).
PMID- 11013238
TI - Eosinophil peroxidase oxidation of thiocyanate. Characterization of major
reaction products and a potential sulfhydryl-targeted cytotoxicity system.
AB - Although the pseudohalide thiocyanate (SCN(-)) is the preferred substrate for
eosinophil peroxidase (EPO) in fluids of physiologic halide composition, the
product(s) of this reaction have not been directly identified, and mechanisms
underlying their cytotoxic potential are poorly characterized. We used nuclear
magnetic resonance spectroscopy (NMR), electrospray ionization mass spectrometry,
and quantitative chemical analysis to identify the principal reaction products of
both the EPO/SCN(-)/H(2)O(2) system and activated eosinophils as roughly
equimolar amounts of OSCN(-) (hypothiocyanite) and OCN(-) (cyanate). Red blood
cells exposed to increasing concentrations of OSCN(-)/OCN(-) are first depleted
of glutathione, after which glutathione S-transferase and glyceraldehyde-3
phosphate dehydrogenase then ATPases undergo sulfhydryl (SH) reductant-reversible
inactivation before lysing. OSCN(-)/OCN(-) inactivates red blood cell membrane
ATPases 10-1000 times more potently than do HOCl, HOBr, and H(2)O(2). Exposure of
glutathione S-transferase to [(14)C]OSCN(-)/OCN(-) causes SH reductant-reversible
disulfide bonding and covalent isotope labeling. We propose that EPO/SCN(
)/H(2)O(2) reaction products comprise a potential SH-targeted cytotoxic system
that functions in striking contrast to HOCl, the highly but relatively
indiscriminantly reactive product of the neutrophil myeloperoxidase system.
PMID- 11013239
TI - Specific desensitization of glycogen synthase activation by insulin in 3T3-L1
adipocytes. Connection between enzymatic activation and subcellular localization.
AB - A protocol was developed in 3T3-L1 adipocytes that resulted in the specific
desensitization of glycogen synthase activation by insulin. Cells were pretreated
for 15 min with 100 nm insulin, and then recovered for 1.5 h in the absence of
hormone. Subsequent basal and insulin-induced phosphorylation of the insulin
receptor, IRS-1, MAPK, Akt kinase, and GSK-3 were similar in control and
pretreated cells. Additionally, enhanced glucose transport and incorporation into
lipid in response to insulin were unaffected. However, pretreatment reduced
insulin-stimulated glycogen synthesis by over 50%, due to a nearly complete
inhibition of glycogen synthase activation. Removal of extracellular glucose
during the recovery period blocked the increase in glycogen levels, and restored
insulin-induced glycogen synthase activation. Furthermore, incubation of
pretreated 3T3-L1 adipocytes with glycogenolytic agents reversed the
desensitization event. Separation of cellular lysates on sucrose gradients
revealed that glycogen synthase was primarily located in the dense pellet
fraction, with lesser amounts in the lighter fractions. Insulin induced glycogen
synthase translocation from the lighter to the denser glycogen-containing
fractions. Interestingly, insulin preferentially activated translocated enzyme
while having little effect on the majority of glycogen synthase activity in the
pellet fraction. In insulin-pretreated cells, glycogen synthase did not return to
the lighter fractions during recovery, and thus did not move in response to the
second insulin exposure. These results suggest that, in 3T3-L1 adipocytes, the
translocation of glycogen synthase may be an important step in the regulation of
glycogen synthesis by insulin. Furthermore, intracellular glycogen levels can
regulate glycogen synthase activation, potentially through modulation of
enzymatic localization.
PMID- 11013240
TI - A loss of function mutant of the presenilin homologue SEL-12 undergoes aberrant
endoproteolysis in Caenorhabditis elegans and increases abeta 42 generation in
human cells.
AB - The familial Alzheimer's disease-associated presenilins (PSs) occur as a dimeric
complex of proteolytically generated fragments, which functionally supports
endoproteolysis of Notch and the beta-amyloid precursor protein (betaAPP). A
homologous gene, sel-12, has been identified in Caenorhabditis elegans. We now
demonstrate that wild-type (wt) SEL-12 undergoes endoproteolytic cleavage in C.
elegans similar to the PSs in human tissue. In contrast, SEL-12 C60S protein
expressed from the sel-12(ar131) allele is miscleaved in C. elegans, resulting in
a larger mutant N-terminal fragment. Neither SEL-12 wt nor C60S undergo
endoproteolytic processing upon expression in human cells, suggesting that SEL-12
is cleaved by a C. elegans-specific endoproteolytic activity. The loss of
function of sel-12 in C. elegans is not associated with a dominant negative
activity in human cells, because SEL-12 C60S and the corresponding PS1 C92S
mutation do not interfere with Notch1 cleavage. Moreover, both mutant variants
increase the aberrant production of the highly amyloidogenic 42-amino acid
version of amyloid beta-peptide similar to familial Alzheimer's disease
associated human PS mutants. Our data therefore demonstrate that the C60S
mutation in SEL-12 is associated with aberrant endoproteolysis and a loss of
function in C. elegans, whereas a gain of misfunction is observed upon expression
in human cells.
PMID- 11013241
TI - Thyroglobulin is selected as luminal protein cargo for apical transport via
detergent-resistant membranes in epithelial cells.
AB - Thyroid hormone synthesis by thyrocytes depends upon apical secretion of
thyroglobulin (Tg), the glycoprotein prohormone. In stably transfected MDCK
cells, recombinant Tg is also secreted apically. All secreted Tg has undergone
Golgi carbohydrate modification, whereas most intracellular Tg (which is slow to
exit the endoplasmic reticulum) is sensitive to digestion with endoglycosidase H.
However, in MDCK cells and PC Cl3 thyrocytes, a subpopulation of newly
synthesized recombinant and endogenous Tg, respectively, is recovered in a Triton
X-100 insoluble, glycosphingolipid/cholesterol-enriched (GEM/raft) fraction, and
this small subpopulation is overwhelmingly endoglycosidase H resistant. Upon
apical secretion, Tg solubility is restored. Apical secretion of Tg is inhibited
by cellular cholesterol depletion. In FRT cells, recombinant Tg becomes Triton X
100 insoluble within 60 min after synthesis and a portion is actually
endoglycosidase H-sensitive, suggesting early Tg entry into GEMs/rafts.
Interestingly in FRT cells, Tg remains associated with the apical plasma membrane
upon exocytosis, and all surface Tg is GEM/raft-associated. Thus, Tg is the first
secretory protein demonstrated to enter Triton X-100 insoluble membranes en route
to the apical surface of epithelial cells. The data imply that Tg utilizes a
cargo-selective mechanism for apical sorting.
PMID- 11013242
TI - Reverse methionine biosynthesis from S-adenosylmethionine in eukaryotic cells.
AB - The intracellular ratio between methionine and its activated form S
adenosylmethionine (AdoMet) is of crucial importance for the one-carbon
metabolism. AdoMet recycling into methionine was believed to be largely achieved
through the methyl and the thiomethyladenosine cycles. We show here that in
yeast, AdoMet recycling actually occurs mainly through the direct AdoMet
dependent remethylation of homocysteine. Compelling evidences supporting this
result were obtained owing to the identification and functional characterization
of two new genes, SAM4 and MHT1, that encode the yeast AdoMet-homocysteine
methyltransferase and S-methylmethionine-homocysteine methyltransferase,
respectively. Homologs of the Sam4 and Mht1 proteins exist in other eucaryotes,
indicating that such enzymes would be universal and not restricted to the
bacterial or fungal kingdoms. New pathways for AdoMet or S-methylmethionine
dependent methionine synthesis are presented.
PMID- 11013243
TI - Tyrosine 220 in the 5th transmembrane domain of the neuromedin B receptor is
critical for the high selectivity of the peptoid antagonist PD168368.
AB - Peptoid antagonists are increasingly being described for G protein-coupled
receptors; however, little is known about the molecular basis of their binding.
Recently, the peptoid PD168368 was found to be a potent selective neuromedin B
receptor (NMBR) antagonist. To investigate the molecular basis for its
selectivity for the NMBR over the closely related receptor for gastrin-releasing
peptide (GRPR), we used a chimeric receptor approach and a site-directed
mutagenesis approach. Mutated receptors were transiently expressed in Balb 3T3.
The extracellular domains of the NMBR were not important for the selectivity of
PD168368. However, substitution of the 5th upper transmembrane domain (uTM5) of
the NMBR by the comparable GRPR domains decreased the affinity 16-fold. When the
reverse study was performed by substituting the uTM5 of NMBR into the GRPR, a 9
fold increase in affinity occurred. Each of the 4 amino acids that differed
between NMBR and GRPR in the uTM5 region were exchanged, but only the
substitution of Phe(220) for Tyr in the NMBR caused a decrease in affinity. When
the reverse study was performed to attempt to demonstrate a gain of affinity in
the GRPR, the substitution of Tyr(219) for Phe caused an increase in affinity.
These results suggest that the hydroxyl group of Tyr(220) in uTM5 of NMBR plays a
critical role for high selectivity of PD168368 for NMBR over GRPR. Receptor and
ligand modeling suggests that the hydroxyl of the Tyr(220) interacts with
nitrophenyl group of PD168368 likely primarily by hydrogen bonding. This result
shows the selectivity of the peptoid PD168368, similar to that reported for
numerous non-peptide analogues with other G protein-coupled receptors, is
primarily dependent on interaction with transmembrane amino acids.
PMID- 11013244
TI - Hepatocyte growth factor activator inhibitor type 1 is a specific cell surface
binding protein of hepatocyte growth factor activator (HGFA) and regulates HGFA
activity in the pericellular microenvironment.
AB - Hepatocyte growth factor activator (HGFA) is responsible for proteolytic
activation of the precursor form of hepatocyte growth factor in injured tissues.
To date, two specific inhibitors of HGFA have been identified, namely HGFA
inhibitor type 1 (HAI-1) and type 2 (HAI-2)/placental bikunin (PB). Both
inhibitors are first synthesized as integral membrane proteins having two Kunitz
domains and a transmembrane domain, and are subsequently released from cell
surface by shedding. Here we show that an active form of HGFA is specifically
complexed with membrane-form HAI-1, but not with HAI-2/PB, on the surface of
epithelial cells expressing both inhibitors. This binding required the enzyme
activity of HGFA. The selective binding of HGFA to the cell surface HAI-1 was
further confirmed in an engineered system using Chinese hamster ovary cells, in
which only the cells expressing HAI-1 retained exogenous HGFA. The binding of
HGFA to HAI-1 was reversible, and no irreversible modifications affecting the
enzyme activity occurred during the binding. Importantly, HAI-1 and the HGFA.HAI
1 complex were quickly released from the cell surface by treatment with phorbol
12-myristate 13-acetate or interleukin 1beta accompanying the generation of 58
kDa fragments of HAI-1, which are less potent against HGFA, as well as
significant recovery of HGFA activity in the culture supernatant. This regulated
shedding was completely inhibited by BB3103, a synthetic zinc-metalloproteinase
inhibitor. We conclude that HAI-1 is not only an inhibitor but also a specific
acceptor of active HGFA, acting as a reservoir of this enzyme on the cell
surface. The latter property appears to ensure the concentrated pericellular HGFA
activity in certain cellular conditions, such as tissue injury and inflammation,
via the up-regulated shedding of HGFA.HAI-1 complex. These findings shed light on
a novel function of the integral membrane Kunitz-type inhibitor in the regulation
of pericellular proteinase activity.
PMID- 11013245
TI - p13(SUC1) and the WW domain of PIN1 bind to the same phosphothreonine-proline
epitope.
AB - The WW domain of the human PIN1 and p13(SUC1), a subunit of the cyclin-dependent
kinase complex, were previously shown to be involved in the regulation of the
cyclin-dependent kinase complex activity at the entry into mitosis, by an
unresolved molecular mechanism. We report here experimental evidence for the
direct interaction of p13(SUC1) with a model CDC25 peptide, dependent on the
phosphorylation state of its threonine. Chemical shift perturbation of backbone
(1)H(N), (15)N, and (13)Calpha resonances during NMR titration experiments allows
accurate identification of the binding site, primarily localized around the anion
binding site, occupied in the crystal structure of the homologous p9(CKSHs2) by a
sulfate molecule. The epitope recognized by p13(SUC1) includes the proline at
position +1 of the phosphothreonine, as was shown by the decrease in affinity for
a mutated CDC25 phosphopeptide, containing an alanine/proline substitution. No
direct interaction between the PIN1 WW domain or its catalytic proline cis/trans
isomerase domain and p13(SUC1) was detected, but our study showed that in vitro
the WW domain of the human PIN1 antagonizes the binding of the p13(SUC1) to the
CDC25 phosphopeptide, by binding to the same phosphoepitope. We thus propose that
the full cyclin-dependent kinase complex stimulates the phosphorylation of CDC25
through binding of its p13(SUC1) module to the phosphoepitope of the substrate
and that the reported WW antagonism of p13(SUC1)-stimulated CDC25 phosphorylation
is caused by competitive binding of both protein modules to the same
phosphoepitope.
PMID- 11013246
TI - Tau filament formation in transgenic mice expressing P301L tau.
AB - Mutations in the microtubule-associated protein tau, including P301L, are
genetically coupled to hereditary frontotemporal dementia with parkinsonism
linked to chromosome 17. To determine whether P301L is associated with fibril
formation in mice, we expressed the longest human tau isoform, human tau40, with
this mutation in transgenic mice by using the neuron-specific mouse Thy1.2
promoter. We obtained mice with high expression of human P301L tau in cortical
and hippocampal neurons. Accumulated tau was hyperphosphorylated and translocated
from axonal to somatodendritic compartments and was accompanied by astrocytosis
and neuronal apoptosis indicated by terminal deoxynucleotidyl transferase
mediated biotinylated dUTP nick end-labeling staining. Moreover, P301L tau formed
abnormal filaments. Electron microscopy of sarcosyl-insoluble protein extracts
established that the filaments had a straight or twisted structure of variable
length and were approximately 15 nm wide. Immunoelcecton microscopy showed that
the tau filaments were phosphorylated at the TG3, AT100, AT8, and AD199 epitopes
in vivo. In cortex, brain stem, and spinal cord, neurofibrillary tangles were
also identified by thioflavin-S fluorescent microscopy and Gallyas silver stains.
Together, our results show that expression of the P301L mutation in mice causes
neuronal lesions that are similar to those seen in human tauopathies.
PMID- 11013247
TI - Calmodulin kinase II attenuation of gene transcription by preventing cAMP
response element-binding protein (CREB) dimerization and binding of the CREB
binding protein.
AB - Calmodulin Kinase II (CamKII) inhibits the transcription of many CRE-dependent
genes, but the mechanism of dominant transcriptional inhibition is unknown. Here
we show that phosphorylation of serine 142 in CREB by CamKII leads to
dissociation of the CREB dimer without impeding DNA binding capacity. CamKII
modified CREB binds to DNA efficiently as a monomer; however, monomeric CREB is
unable to recruit the CREB-binding protein (CBP) even when phosphorylated at
serine 133. Thus, CamKII confers a dominant inhibitory effect on transcription by
preventing dimerization of CREB, and this mechanism may account for the
attenuation of gene expression.
PMID- 11013248
TI - Intrinsically bent DNA in the promoter regions of the yeast GAAL1-10 and GAL80
genes.
AB - Circular permutation analysis has detected fairly strong sites of intrinsic DNA
bending on the promoter regions of the yeast GAL1-10 and GAL80 genes. These bends
lie in functionally suggestive locations. On the promoter of the GAL1-10
structural genes, strong bends bracket nucleosome B, which lies between the
UAS(G) and the GAL1 TATA. These intrinsic bends could help position nucleosome B.
Nucleosome B plus two other promoter nucleosomes protect the TATA and start site
elements in the inactive state of expression but are completely disrupted
(removed) when GAL1-10 expression is induced. The strongest intrinsic bend (
approximately 70 degrees ) lies at the downstream edge of nucleosome B; this
places it approximately 30 base pairs upstream of the GAL1 TATA, a position that
could allow it to be involved in GAL1 activation in several ways, including the
recruitment of a yeast HMG protein that is required for the normally robust level
of GAL1 expression in the induced state (Paull, T., Carey, M., and Johnson, R.
(1996) Genes Dev. 10, 2769-2781). On the regulatory gene GAL80, the single bend
lies in the non-nucleosomal hypersensitive region, between a GAL80-specific far
upstream promoter element and the more gene-proximal promoter elements. GAL80
promoter region nucleosomes contain no intrinsically bent DNA.
PMID- 11013249
TI - A single arginyl residue in plastocyanin and in cytochrome c(6) from the
cyanobacterium Anabaena sp. PCC 7119 is required for efficient reduction of
photosystem I.
AB - Positively charged plastocyanin from Anabaena sp. PCC 7119 was investigated by
site-directed mutagenesis. The reactivity of its mutants toward photosystem I was
analyzed by laser flash spectroscopy. Replacement of arginine at position 88,
which is adjacent to the copper ligand His-87, by glutamine and, in particular,
by glutamate makes plastocyanin reduce its availability for transferring
electrons to photosystem I. Such a residue in the copper protein thus appears to
be isofunctional with Arg-64 (which is close to the heme group) in cytochrome
c(6) from Anabaena (Molina-Heredia, F. P., Diaz-Quintana, A., Hervas, M.,
Navarro, J. A., and De la Rosa, M. A. (1999) J. Biol. Chem. 274, 33565-33570) and
Synechocystis (De la Cerda, B., Diaz-Quintana, A., Navarro, J. A. , Hervas, M.,
and De la Rosa, M. A. (1999) J. Biol. Chem. 274, 13292-13297). Other mutations
concern specific residues of plastocyanin either at its positively charged east
face (D49K, H57A, H57E, K58A, K58E, Y83A, and Y83F) or at its north hydrophobic
pole (L12A, K33A, and K33E). Mutations altering the surface electrostatic
potential distribution allow the copper protein to modulate its kinetic
efficiency: the more positively charged the interaction site, the higher the rate
constant. Whereas replacement of Tyr-83 by either alanine or phenylalanine has no
effect on the kinetics of photosystem I reduction, Leu-12 and Lys-33 are
essential for the reactivity of plastocyanin.
PMID- 11013250
TI - Evidence that silencing of the HPRT promoter by DNA methylation is mediated by
critical CpG sites.
AB - The strong correlation between promoter hypermethylation and gene silencing
suggests that promoter methylation represses transcription. To identify
methylation sites that may be critical for maintaining repression of the human
HPRT gene, we treated human/hamster hybrid cells containing an inactive human X
chromosome with the DNA demethylating agent 5-azadeoxycytidine (5aCdr), and we
then examined the high resolution methylation pattern of the HPRT promoter in
single cell-derived lines. Reactivation of HPRT correlated with complete promoter
demethylation. In contrast, the 61 5aCdr-treated clones that failed to reactivate
HPRT exhibited sporadic promoter demethylation. However, three specific CpG sites
remained methylated in all unreactivated clones, suggesting these sites may be
critical for maintaining transcriptional silencing of the HPRT gene. Re-treatment
of partially demethylated (and unreactivated) clones with a second round of 5aCdr
did not increase the frequency of HPRT reactivation. This is consistent with
mechanisms of methylation-mediated repression requiring methylation at specific
critical sites and argues against models invoking overall levels or a threshold
of promoter methylation. Treatment of cells with the histone deacetylase
inhibitor, trichostatin A, failed to reactivate HPRT on the inactive X
chromosome, even when the promoter was partially demethylated by 5aCdr treatment,
suggesting that transcriptional repression by DNA methylation is unlikely to
depend upon a trichostatin A-sensitive histone deacetylase.
PMID- 11013251
TI - High and low levels of cottontail rabbit papillomavirus E2 protein generate
opposite effects on gene expression.
AB - The papillomavirus E2 protein plays an important role in viral transcriptional
regulation and replication. We chose to study the cottontail rabbit
papillomavirus (CRPV) E2 protein as a transcriptional regulator because of the
availability of an animal model for papilloma formation, which may be relevant
for human papillomavirus (HPV) infection and replication. We studied the effect
of expression levels of E2 on the long control region, which contains
transcriptional promoter and enhancer elements, and synthetic E2-dependent
artificial promoters in which the E2 was the dominant factor in the
transcriptional activation. These experiments indicated that high levels of E2
were inhibitory and low levels were stimulatory for transactivation. In addition,
we showed that the complex formed between CRPV E2 and the cognate binding site
was less stable than the complex formed between HPV E2 and the same cognate
binding site. Furthermore, we showed that CRPV E2 binding to its transcriptional
regulatory sequence was stabilized by other proteins such as E1, which produced
increments in transcriptional activation of E2-dependent genes. The data may be
used to define conditions in which the rabbit model can be used for the screening
of drugs which are inhibitory to the HPV and CRPV replication and gene
expression.
PMID- 11013253
TI - The gene encoding p202, an interferon-inducible negative regulator of the p53
tumor suppressor, is a target of p53-mediated transcriptional repression.
AB - The p53 tumor suppressor protein regulates the transcription of regulatory genes
involved in cell cycle arrest and apoptosis. We reported previously that
overexpression of p202, an interferon-inducible negative regulator of cell
growth, negatively regulates the transcriptional activity of p53. Now we identify
the gene encoding p202 as one whose mRNA and protein expression decrease in cells
following the expression of wild-type, but not mutant, p53. Furthermore, the
levels of p202 also decrease after exposure of cells to ultra violet light, which
correlate with increase in the levels of p53. We report that the sequence
specific DNA binding of p53 to the 5'-regulatory region of the 202 gene
contributes to the transcriptional repression of the 202 gene. Interestingly,
overexpression of p202 in cells induced to undergo p53-dependent apoptosis
significantly delays this process, indicating that the negative regulation of the
202 gene by wild-type p53 is important to potentiate apoptosis.
PMID- 11013254
TI - Aldehyde dehydrogenase 6, a cytosolic retinaldehyde dehydrogenase prominently
expressed in sensory neuroepithelia during development.
AB - We have isolated the chick and mouse homologs of human aldehyde dehydrogenase 6
(ALDH6) that encode a third cytosolic retinaldehyde-specific aldehyde
dehydrogenase. In both chick and mouse embryos, strong expression is observed in
the sensory neuroepithelia of the head. In situ hybridization analysis in chick
shows compartmentalized expression primarily in the ventral retina, olfactory
epithelium, and otic vesicle; additional sites of expression include the isthmus,
Rathke's pouch, posterior spinal cord interneurons, and developing limbs.
Recombinant chick ALDH6 has a K(0.5) = 0.26 microm, V(max) = 48.4 nmol/min/mg and
exhibits strong positive cooperativity (H = 1.9) toward all-trans-retinaldehyde;
mouse ALDH6 has similar kinetic parameters. Expression constructs can confer 1000
fold increased sensitivity to retinoic acid receptor-dependent signaling from
retinol in transient transfections experiments. The localization of ALDH6 to the
developing sensory neuroepithelia of the eye, nose, and ear and discreet sites
within the CNS suggests a role for RA signaling during primary neurogenesis at
these sites.
PMID- 11013255
TI - Cloning and characterization of the human activity-dependent neuroprotective
protein.
AB - We have recently cloned the mouse activity-dependent neuroprotective protein
(ADNP). Here, we disclose the cloning of human ADNP (hADNP) from a fetal brain
cDNA library. Comparative sequence analysis of these two ADNP orthologs indicated
90% identity at the mRNA level. Several single nucleotide polymorphic sites were
noticed. The deduced protein structure contained nine zinc fingers, a proline
rich region, a nuclear bipartite localization signal, and a homeobox domain
profile, suggesting a transcription factor function. Further comparative analysis
identified an ADNP paralog (33% identity and 46% similarity), indicating that
these genes belong to a novel protein family with a nine-zinc finger motif
followed by a homeobox domain. The hADNP gene structure spans approximately 40
kilobases and includes five exons and four introns with alternative splicing of
an untranslated second exon. The hADNP gene was mapped to chromosome 20q12-13.2,
a region associated with aggressive tumor growth, frequently amplified in many
neoplasias, including breast, bladder, ovarian, pancreatic, and colon cancers.
hADNP mRNA is abundantly expressed in distinct normal tissues, and high
expression levels were encountered in malignant cells. Down-regulation of ADNP by
antisense oligodeoxynucleotides up-regulated the tumor suppressor p53 and reduced
the viability of intestinal cancer cells by 90%. Thus, ADNP is implicated in
maintaining cell survival, perhaps through modulation of p53.
PMID- 11013256
TI - The loop region covering the iron-sulfur cluster in bovine adrenodoxin comprises
a new interaction site for redox partners.
AB - The amino acid in position 49 in bovine adrenodoxin is conserved among vertebrate
[2Fe-2S] ferredoxins as hydroxyl function. A corresponding residue is missing in
the cluster-coordinating loop of plant-type [2Fe-2S] ferredoxins. To probe the
function of Thr-49 in a vertebrate ferredoxin, replacement mutants T49A, T49S,
T49L, and T49Y, and a deletion mutant, T49Delta, were generated and expressed in
Escherichia coli. CD spectra of purified proteins indicate changes of the [2Fe
2S] center geometry only for mutant T49Delta, whereas NMR studies reveal no
transduction of structural changes to the interaction domain. The redox potential
of T49Delta (-370 mV) is lowered by approximately 100 mV compared with wild type
adrenodoxin and reaches the potential range of plant-type ferredoxins (-305 to
455 mV). Substitution mutants show moderate changes in the binding affinity to
the redox partners. In contrast, the binding affinity of T49Delta to adrenodoxin
reductase and cytochrome P-450 11A1 (CYP11A1) is dramatically reduced. These
results led to the conclusion that Thr-49 modulates the redox potential in
adrenodoxin and that the cluster-binding loop around Thr-49 represents a new
interaction region with the redox partners adrenodoxin reductase and CYP11A1. In
addition, variations of the apparent rate constants of all mutants for CYP11A1
reduction indicate the participation of residue 49 in the electron transfer
pathway between adrenodoxin and CYP11A1.
PMID- 11013257
TI - The thioredoxin system of the malaria parasite Plasmodium falciparum. Glutathione
reduction revisited.
AB - In most living cells, redox homeostasis is based both on the glutathione and the
thioredoxin system. In the malaria parasite Plasmodium falciparum antioxidative
proteins represent promising targets for the development of antiparasitic drugs.
We cloned and expressed a thioredoxin of P. falciparum (pftrx), and we improved
the stable expression of the thioredoxin reductase (PfTrxR) of the parasite by
multiple silent mutagenesis. Both proteins were biochemically characterized and
compared with the human host thioredoxin system. Intriguingly, the 13-kDa protein
PfTrx is a better substrate for human TrxR (K(m) = 2 microm, k(cat) = 3300 min(
)(1)) than for P. falciparum TrxR (K(m) = 10.4 microm, k(cat) = 3100 min(-)(1)).
Possessing a midpoint potential of -270 mV, PfTrx was found to reduce the disease
related metabolites S-nitrosoglutathione and GSSG. The rate constant k(2) for the
reaction between reduced P. falciparum thioredoxin and GSSG was determined to be
0.039 microm(-)(1) min(-)(1) at 25 degrees C and pH 7.4. The k(2) for
thioredoxins from man, Drosophila melanogaster, and Escherichia coli was
approximately 5 times lower. Our data suggest that GSSG reduction can be
supported at a high rate by the TrxR/Trx system in glutathione reductase
deficient cells; this may be relevant for certain stages of the malarial parasite
but also for cells containing high [GSSG] of other organisms like dormant forms
of Neurospora, glutathione reductase-deficient yeast mutants, or CD4(+)
lymphocytes of AIDS patients.
PMID- 11013258
TI - Two basic residues of the h-VPAC1 receptor second transmembrane helix are
essential for ligand binding and signal transduction.
AB - We mutated the vasoactive intestinal peptide (VIP) Asp(3) residue and two VPAC(1)
receptor second transmembrane helix basic residues (Arg(188) and Lys(195)). VIP
had a lower affinity for R188Q, R188L, K195Q, and K195I VPAC(1) receptors than
for VPAC(1) receptors. [Asn(3)] VIP and [Gln(3)] VIP had lower affinities than
VIP for VPAC(1) receptors but higher affinities for the mutant receptors; the two
basic amino acids facilitated the introduction of the negatively charged
aspartate inside the transmembrane domain. The resulting interaction was
necessary for receptor activation. 1/[Asn(3)] VIP and [Gln(3)] VIP were partial
agonists at VPAC(1) receptors; 2/VIP did not fully activate the K195Q, K195I,
R188Q, and R188L VPAC(1) receptors; a VIP analogue ([Arg(16)] VIP) was more
efficient than VIP at the four mutated receptors; and [Asn(3)] VIP and [Gln(3)]
VIP were more efficient than VIP at the R188Q and R188L VPAC(1) receptors; 3/the
[Asp(3)] negative charge did not contribute to the recognition of the VIP(1)
antagonist, [AcHis(1),D-Phe(2),Lys(15),Arg(16),Leu(27)] VIP ()/growth hormone
releasing factor (8-27). This is the first demonstration that, to activate the
VPAC(1) receptor, the Asp(3) side chain of VIP must penetrate within the
transmembrane domain, in close proximity to two highly conserved basic amino
acids from transmembrane 2.
PMID- 11013260
TI - Transmembrane topology of the secretory Na+-K+-2Cl- cotransporter NKCC1 studied
by in vitro translation.
AB - The secretory Na(+)-K(+)-2Cl(-) cotransporter NKCC1 is a member of a small gene
family of electroneutral salt transporters. Hydropathy analyses indicate that all
of these transporters have a similar general structure consisting of large
hydrophilic N and C termini on either side of a central, relatively well
conserved, hydrophobic domain. Programs that predict the transmembrane topology
of polytopic membrane proteins identify 10-12 putative membrane-spanning segments
(MSSs) in this hydrophobic domain; but to date, there is little experimental data
on the structure of this region for any of these transporters. In this report, we
have studied the transmembrane topology of NKCC1 using an in vitro translation
system designed to test the membrane insertion properties of putative MSSs
(Bamberg, K., and Sachs, G. (1994) J. Biol. Chem. 269, 16909-16919). Fusion
proteins consisting of putative NKCC1 MSSs inserted either (i) between an N
terminal cytosolic anchor sequence and a C-terminal reporter sequence containing
multiple N-linked glycosidation sites or (ii) between an N-terminal signal anchor
sequence and the same glycosidation flag were expressed in the presence of canine
pancreatic microsomes. The glycosidation status of the reporter sequence, which
indicated its luminal or extraluminal location in the microsomes, was then used
to characterize the signal anchor or stop transfer activity of the inserted MSSs.
The results of this experimental analysis yielded a topology scheme consisting of
12 membrane-spanning segments, two pairs of which apparently form rather tight
hairpin-like structures within the membrane.
PMID- 11013259
TI - Identification of residues within the drug-binding domain of the human multidrug
resistance P-glycoprotein by cysteine-scanning mutagenesis and reaction with
dibromobimane.
AB - P-glycoprotein (P-gp) can transport a wide variety of cytotoxic compounds that
have diverse structures. Therefore, the drug-binding domain of the human
multidrug resistance P-gp likely consists of residues from multiple transmembrane
(TM) segments. In this study, we completed cysteine-scanning mutagenesis of all
the predicted TM segments of P-gp (TMs 1-5 and 7-10) and tested for inhibition by
a thiol-reactive substrate (dibromobimane) to identify residues within the drug
binding domain. The activities of 189 mutants were analyzed. Verapamil-stimulated
ATPase activities of seven mutants (Y118C and V125C (TM2), S222C (TM4), I306C
(TM5), S766C (TM9), and I868C and G872C (TM10)) were inhibited by more than 50%
by dibromobimane. The activities of mutants S222C (TM4), I306C (TM5), I868C
(TM10), and G872C (TM10), but not that of mutants Y118C (TM2), V125C (TM2), and
S776C (TM9), were protected from inhibition by dibromobimane by pretreatment with
verapamil, vinblastine, or colchicine. These results and those from previous
studies (Loo, T. W. and Clarke, D. M. (1997) J. Biol. Chem. 272, 31945-31948;
Loo, T. W. and Clarke, D. M. (1999) J. Biol. Chem. 274, 35388-35392) indicate
that the drug-binding domain of P-gp consists of residues in TMs 4, 5, 6, 10, 11,
and 12.
PMID- 11013261
TI - The immunophilin-like protein XAP2 regulates ubiquitination and subcellular
localization of the dioxin receptor.
AB - The dioxin (aryl hydrocarbon) receptor is a ligand-dependent transcription factor
that induces expression of a number of genes encoding drug metabolizing enzymes.
The nonactivated form of the dioxin receptor is associated with heat shock
protein (hsp) 90, the co-chaperone p23, and the immunophilin-like protein XAP2.
Whereas hsp90 has a role in maintenance of the high-affinity ligand binding
conformation of the dioxin receptor complex, and p23 stabilizes receptor-hsp90
interaction, the exact role of XAP2 is largely unknown. Here we show that XAP2
protected the ligand-free form of receptor against ubiquitination, resulting in
increased dioxin receptor protein levels. Upon exposure to ligand, nuclear
translocation of the dioxin receptor was markedly delayed by XAP2, indicating an
additional role of XAP2 in regulation of the subcellular localization of the
receptor by a mechanism of cytoplasmic retention. In order to mediate these
effects, XAP2 required stable association with the hsp90-p23 molecular chaperone
complex. The association of XAP2 as well as p23 with the dioxin receptor was
determined by the functional state of hsp90. These data indicate a novel mode of
regulation of dioxin receptor signaling by the hsp90-dependent molecular
chaperone machinery.
PMID- 11013262
TI - Protein-tyrosine phosphatase D1, a potential regulator and effector for Tec
family kinases.
AB - Etk, also named Bmx, is a member of the Tec tyrosine kinase family, which is
characterized by a multimodular structure including a pleckstrin homology (PH)
domain, an SH3 domain, an SH2 domain, and a catalytic domain. The signaling
mechanisms regulating Etk kinase activity remain largely unknown. To identify
factor(s) regulating Etk activity, we used the PH domain and a linker region of
Etk as a bait for a yeast two-hybrid screen. Three independent clones encoding
protein-tyrosine phosphatase D1 (PTPD1) fragments were isolated. The binding of
PTPD1 to Etk is specific since PTPD1 cannot associate with either the Akt PH
domain or lamin. In vitro and in vivo binding studies demonstrated that PTPD1 can
interact with Etk and that residues 726-848 of PTPD1 are essential for this
interaction. Deletion analysis of Etk indicated that the PH domain is essential
for PTPD1 interaction. Furthermore, the Etk-PTPD1 interaction stimulated the
kinase activity of Etk, resulting in an increased phosphotyrosine content in both
factors. The Etk-PTPD1 interaction also increased Stat3 activation. The effect of
PTPD1 on Etk activation is specific since PTPD1 cannot potentiate Jak2 activity
upon Stat3 activation. In addition, Tec (but not Btk) kinase can also be
activated by PTPD1. Taken together, these findings indicate that PTPD1 can
selectively associate with and stimulate Tec family kinases and modulate Stat3
activation.
PMID- 11013263
TI - A novel nuclear receptor corepressor complex, N-CoR, contains components of the
mammalian SWI/SNF complex and the corepressor KAP-1.
AB - Transcriptional silencing by many transcription factors is mediated by the
nuclear receptor corepressor (N-CoR). The mechanism by which N-CoR represses
basal transcription involves the direct or indirect recruitment of histone
deacetylases (HDACs). We have isolated two multiprotein N-CoR complexes,
designated N-CoR-1 and N-CoR-2, which possess histone deacetylase activity that
is mediated by distinct HDACs. Based on Western blotting using antibodies against
known subunits, the only HDAC found in the N-CoR-1 complex was HDAC3. In
contrast, N-CoR-2 contained predominantly HDAC1 and HDAC2 as well as several
other subunits that are found in the Sin3A.HDAC complex. Using mass spectrometry
and Western blotting, we have identified several novel components of the N-CoR-1
complex including the SWI/SNF-related proteins BRG1, BAF 170, BAF 155, BAF
47/INI1, and the corepressor KAP-1 that is involved in silencing heterochromatin.
Indirect immunofluorescence has revealed that both KAP-1 and N-CoR colocalize
throughout the nucleus. These results suggest that N-CoR is found in distinct
multiprotein complexes, which are involved in multiple pathways of
transcriptional repression.
PMID- 11013264
TI - Use of diethyl(2-methylpyrrolidin-2-yl)phosphonate as a highly sensitive extra-
and intracellular 31P NMR pH indicator in isolated organs. Direct NMR evidence of
acidic compartments in the ischemic and reperfused rat liver.
AB - The novel phosphorylated pyrrolidine diethyl(2-methylpyrrolidin-2-yl)phosphonate
(DEPMPH) was evaluated as a (31)P NMR probe of the pH changes associated with
ischemia/reperfusion of rat isolated hearts and livers. In vitro titration curves
indicated that DEPMPH exhibited a 4-fold larger amplitude of chemical shift
variation than inorganic phosphate yielding an enhanced NMR sensitivity in the pH
range of 5.0-7.5 that allowed us to assess pH variations of less than 0.1 pH
units. At the non-toxic concentration of 5 mm, DEPMPH distributed into external
and cytosolic compartments in both normoxic organs, as assessed by the appearance
of two resonance peaks. An additional peak was observed in normoxic and ischemic
livers, assigned to DEPMPH in acidic vesicles (pH 5.3-5.6). During severe
myocardial ischemia, a third peak corresponding to DEPMPH located in ventricular
and atrial cavities appeared (pH 6.9). Mass spectrometry and NMR analyses of
perchloric extracts showed that no significant metabolism of DEPMPH occurred in
the ischemic liver. Reperfusion with plain buffer resulted in a rapid washout of
DEPMPH from both organs. It was concluded that the highly pH-sensitive DEPMPH
could be of great interest in noninvasive ex vivo studies of pH gradients that
may be involved in many pathological processes.
PMID- 11013265
TI - Fate of endogenously synthesized cholesterol in Niemann-Pick type C1 cells.
AB - Mammalian cells obtain cholesterol via two pathways: endogenous synthesis in the
endoplasmic reticulum and exogenous sources mainly through the low density
lipoprotein (LDL) receptor pathway. We performed pulse-chase experiments to
monitor the fate of endogenously synthesized cholesterol and showed that, after
reaching the plasma membrane from the endoplasmic reticulum, the newly
synthesized cholesterol eventually accumulates in an internal compartment in
Niemann-Pick type C1 (NPC1) cells. Thus, the ultimate fate of endogenously
synthesized cholesterol in NPC1 cells is the same as LDL-derived cholesterol.
However, the time required for endogenous cholesterol to accumulate internally is
much slower than LDL-derived cholesterol. Different pathways thus govern the post
plasma membrane trafficking of endogenous cholesterol and LDL-derived cholesterol
to the internal compartment. Results using the inhibitor N-butyldeoxynojirimycin,
which depletes cellular complex glycosphingolipids, demonstrates that the
cholesterol trafficking defect in NPC1 cells is not caused by ganglioside
accumulation. The ultimate cause of death in NPC disease is progressive
neurological deterioration in the central nervous system, where the major source
of cholesterol is derived from endogenous synthesis. Our current study provides a
plausible link between defects in intracellular trafficking of endogenous
cholesterol and the etiology of Niemann-Pick type C disease.
PMID- 11013266
TI - Inhibition of Trypanosoma brucei gene expression by RNA interference using an
integratable vector with opposing T7 promoters.
AB - RNA interference is a powerful method for inhibition of gene expression in
Trypanosoma brucei (Ngo, H., Tschudi, C., Gull, K., and Ullu, E. (1998) Proc.
Natl. Acad. Sci. U. S. A. 95, 14687-14692). Here we describe a vector (pZJM) for
in vivo tetracycline-inducible synthesis of double-stranded RNA (dsRNA) in stably
transformed cells. The dsRNA is synthesized from opposing T7 promoters. We tested
the vector with genes involved in processes such as kinetoplast DNA replication,
mitochondrial mRNA synthesis, glycosyl phosphatidylinositol biosynthesis,
glycosome biogenesis, and polyamine biosynthesis. In most cases the induction of
dsRNA caused specific and dramatic loss of the appropriate mRNA, and in many
cases there was growth inhibition or cell death. One striking phenotype was the
loss of kinetoplast DNA after interference with expression of a topoisomerase II.
The gene being analyzed by this procedure need not even be fully sequenced. In
fact, many of the genes we tested were derived from partial sequences in the T.
brucei genome data base that were identified by homology with known proteins. It
takes as little as 3 weeks from identification of a gene sequence in the data
base to the appearance of a phenotype.
PMID- 11013268
TI - Perlecan heparan sulfate proteoglycan. A novel receptor that mediates a distinct
pathway for ligand catabolism
PMID- 11013267
TI - Nalpha -terminal acetylation of eukaryotic proteins.
PMID- 11013269
TI - Identification and cloning of two histone fold motif-containing subunits of HeLa
DNA polymerase epsilon
PMID- 11013270
TI - Epstein-Barr virus, the CNS, and AIDS-related lymphomas: as close as flame to
smoke.
PMID- 11013271
TI - Epstein-Barr virus infection is predictive of CNS involvement in systemic AIDS
related non-Hodgkin's lymphomas.
AB - PURPOSE: This study aimed at correlating Epstein-Barr virus (EBV) infection of
systemic AIDS-related non-Hodgkin lymphomas (AIDS-NHL) with the development of a
CNS localization of the tumor. PATIENTS AND METHODS: Demographic, epidemiologic,
clinical, histologic, and virologic features were collected for all systemic AIDS
NHL patients included in the study (n = 50). Pathologic specimens were classified
according to the working formulation for NHL and the Revised European-American
Lymphoma classification. EBV infection in tumor tissue samples was studied by EBV
small encoded RNA in situ hybridization; EBV-DNA detection in CSF was carried out
by nested polymerase chain reaction using Epstein-Barr nuclear antigen-1-specific
primers. In addition, selected EBV-positive lymphomas were subjected to a
detailed characterization of EBV molecular heterogeneity. RESULTS: Eleven
patients had a CNS involvement at some point during their clinical history (four
at diagnosis and seven at relapse). Thirty patients (11 with CNS involvement and
19 without) harbored EBV infection of the tumor. Sensitivity, specificity, and
positive and negative predictive values of EBV-DNA detection in CSF for CNS
involvement by lymphoma were 90%, 100%, 100%, and 97.6%, respectively. Factors
significantly predictive of CNS involvement were EBV infection of the tumor
(P=.003), an extranodal disease at diagnosis other than CNS (P=.006), and a non
CNS relapse (P=.01). In four cases of CNS involvement, EBV-DNA in CSF preceded
any other sign of disease by a mean of 35 days. CONCLUSION: These results show
that EBV infection of the tumor clone significantly increases the risk of CNS
involvement by systemic AIDS-NHL, without regard of specific molecular features.
The detection of EBV-DNA in the CSF of AIDS-NHL patients may select cases with
higher risk of CNS involvement and, therefore, may prove useful in the
therapeutic stratification of these tumors.
PMID- 11013272
TI - Expression of interferon regulatory factor 4 in chronic myeloid leukemia:
correlation with response to interferon alfa therapy.
AB - PURPOSE: Mice experiments have established an important role for interferon
regulatory factor (IRF) family members in hematopoiesis. We wanted to study the
expression of interferon regulatory factor 4 (IRF4) in various hematologic
disorders, especially chronic myeloid leukemia (CML), and its association with
response to interferon alfa (IFN-alpha) treatment in CML. MATERIALS AND METHODS:
Blood samples from various hematopoietic cell lines, different leukemia patients
(70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia
[CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia
patients), and 33 healthy volunteers were monitored for IRF4 expression by
reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the
IRF4 level was determined in sorted cell subpopulations from CML patients and
healthy volunteers and in in vitro-stimulated CML cells. Furthermore, IRF4
expression was compared in the CML samples taken before IFN-alpha therapy and in
47 additional CML samples taken during IFN-alpha therapy. IRF4 expression was
then correlated with cytogenetic response to IFN-alpha. RESULTS: IRF4 expression
was significantly impaired in CML, AML, and CMMoL samples. The downregulation of
IRF4 in CML samples was predominantly found in T cells. In CML patients during
IFN-alpha therapy, a significant increase in IRF4 levels was detected, and this
was also observed in sorted T cells from CML patients. The increase seen during
IFN-alpha therapy was not due to different blood counts. In regard to the
cytogenetic response with IFN-alpha, a good response was associated with high
IRF4 expression. CONCLUSION: IRF4 expression is downregulated in T cells of CML
patients, and its increase is associated with a good response to IFN-alpha
therapy. These data suggest IRF4 expression as a useful marker to monitor, if not
predict, response to IFN-alpha in CML.
PMID- 11013273
TI - Phase III randomized trial of amifostine as a radioprotector in head and neck
cancer.
AB - PURPOSE: Radiotherapy for head and neck cancer causes acute and chronic
xerostomia and acute mucositis. Amifositine and its active metabolite, WR-1065,
accumulate with high concentrations in the salivary glands. This randomized trial
evaluated whether amifostine could ameliorate these side effects without
compromising the effectiveness of radiotherapy in these patients. PATIENTS AND
METHODS: Patients with previously untreated head and neck squamous cell carcinoma
were eligible. Primary end points included the incidence of grade > or =2 acute
xerostomia, grade > or =3 acute mucositis, and grade > or =2 late xerostomia and
were based on the worst toxicity reported. Amifostine was administered (200
mg/m(2) intravenous) daily 15 to 30 minutes before irradiation. Radiotherapy was
given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 Gy. Whole saliva production
was quantitated preradiotherapy and regularly during follow-up. Patients
evaluated their symptoms through a questionnaire during and after treatment.
Local-regional control was the primary antitumor efficacy end point. RESULTS:
Nausea, vomiting, hypotension, and allergic reactions were the most common side
effects. Fifty-three percent of the patients receiving amifostine had at least
one episode of nausea and/or vomiting, but it only occurred with 233 (5%) of
4,314 doses. Amifostine reduced grade > or =2 acute xerostomia from 78% to 51%
(P<.0001) and chronic xerostomia grade > or = 2 from 57% to 34% (P=.002). Median
saliva production was greater with amifostine (0.26 g v 0.10 g, P=.04).
Amifostine did not reduce mucositis. With and without amifostine, 2-year local
regional control, disease-free survival, and overall survival were 58% versus
63%, 53% versus 57%, and 71% versus 66%, respectively. CONCLUSION: Amifostine
reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.
PMID- 11013275
TI - Pretreatment nomogram for predicting the outcome of three-dimensional conformal
radiotherapy in prostate cancer.
AB - PURPOSE: Several studies have defined risk groups for predicting the outcome
after external-beam radiotherapy of localized prostate cancer. However, most
models formed patient risk groups, and none of these models considers radiation
dose as a predictor variable. The purpose of this study was to develop a nomogram
to improve the accuracy of predicting outcome after three-dimensional conformal
radiotherapy. MATERIALS AND METHODS: This study was a retrospective,
nonrandomized analysis of patients treated at the Memorial Sloan-Kettering Cancer
Center between 1988 and 1998. Clinical parameters of the 1,042 patients included
stage, biopsy Gleason score, pretreatment serum prostate-specific antigen (PSA)
level, whether neoadjuvant androgen deprivation therapy was administered, and the
radiation dose delivered. Biochemical (PSA) treatment failure was scored when
three consecutive rises of serum PSA occurred. A nomogram, which predicts the
probability of remaining free from biochemical recurrence for 5 years, was
validated internally on this data set using a bootstrapping method and externally
using a cohort of patients treated at the Cleveland Clinic, Cleveland, OH.
RESULTS: When predicting outcomes for patients in the validation data set from
the Cleveland Clinic, the nomogram had a Somers' D rank correlation between
predicted and observed failure times of 0.52. Predictions from this nomogram were
more accurate (P<.0001) than the best of seven published risk stratification
systems, which achieved a Somers' D coefficient of 0.47. CONCLUSION: The
development process illustrated here produced a nomogram that seems to predict
more accurately than other available systems and may be useful for treatment
selection by both physicians and patients.
PMID- 11013274
TI - High-dose chemotherapy as initial salvage chemotherapy in patients with relapsed
testicular cancer.
AB - PURPOSE: To assess the role of high-dose chemotherapy as initial salvage
chemotherapy in patients with relapsed testicular cancer. PATIENTS AND METHODS:
From August 1992 to April 1998, 65 patients with testicular cancer were treated
with high-dose carboplatin and etoposide followed by peripheral-blood stem-cell
transplantation or autologous bone marrow transplantation rescue as initial
salvage chemotherapy at Indiana University. An identical course was given after
hematopoietic reconstitution. Postchemotherapy resection of residual disease was
performed in selected patients with incomplete radiographic response associated
with normalization of markers. The median follow-up was 39 months (range, 16 to
91 months). RESULTS: Thirty-seven (57%) of the 65 patients are continuously
disease-free. Three additional patients are disease-free with subsequent surgery.
High-dose chemotherapy was associated with significant morbidity but no treatment
related mortality. CONCLUSION: High-dose chemotherapy as initial salvage
chemotherapy achieved impressive long-term survival with acceptable toxicity in
patients with relapsed testicular cancer.
PMID- 11013276
TI - Effect of radiotherapy after breast-conserving treatment in women with breast
cancer and germline BRCA1/2 mutations.
AB - PURPOSE: Recent laboratory data suggest a role for BRCA1/2 in the cellular
response to DNA damage. There is a paucity of clinical data, however, examining
the effect of radiotherapy (RT), which causes double-strand breaks, on breast
tissue from BRCA1/2 mutation carriers. Thus the goals of this study were to
compare rates of radiation-associated complications, in-breast tumor recurrence,
and distant relapse in women with BRCA1/2 mutations treated with breast
conserving therapy (BCT) using RT with rates observed in sporadic disease.
PATIENTS AND METHODS: Seventy-one women with a BRCA1/2 mutation and stage I or II
breast cancer treated with BCT were matched 1:3 with 213 women with sporadic
breast cancer. Conditional logistic regression models were used to compare
matched cohorts for rates of complications and recurrence. RESULTS: Tumors from
women in the genetic cohort were associated with high histologic (P =.0004) and
nuclear (P =.009) grade and negative estrogen (P=.0001) and progesterone (P=.002)
receptors compared with tumors from the sporadic cohort. Using Radiation Therapy
Oncology Group/European Organization for Research and Treatment of Cancer
toxicity scoring, there were no significant differences in acute or chronic
morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial
overall survival, relapse-free survival, and rates of tumor control in the
treated breast for the patients in the genetic cohort were 86%, 78%, and 98%,
respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic
cohort (P = not significant). CONCLUSION: There was no evidence of increased
radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA1/2
germline mutation compared with controls, and rates of tumor control in the
breast and survival were comparable between BRCA1/2 carriers and controls at 5
years. Although additional follow-up is needed, these data may help in discussing
treatment options in the management of early-stage hereditary breast cancer and
should provide reassurance regarding the safety of administering RT to carriers
of a germline BRCA1/2 mutation.
PMID- 11013277
TI - Phase II study of vinorelbine with protracted fluorouracil infusion as a second-
or third-line approach for advanced breast cancer patients previously treated
with anthracyclines.
AB - PURPOSE: To evaluate the feasibility and activity of vinorelbine in association
with protracted infusional fluorouracil in patients with advanced breast cancer
who were previously treated with anthracycline-containing regimens. PATIENTS AND
METHODS: Eighty-three consecutive patients were entered onto the study. Forty
three patients experienced treatment failure or relapse after anthracycline
based, first-line chemotherapy for advanced disease and 29 experienced treatment
failure or relapse after first- and second-line approaches; 11 patients
experienced progressive disease within 6 months of completion of adjuvant
anthracycline therapy. Sites of involvement were as follows: liver involvement,
42 patients (50.6%); lung 24 (28.9%); bone, 49 (59.0%); and skin/lymph nodes, 21
(25.3%). Treatment consisted of vinorelbine 30 mg/m(2) administered on days 1 and
15 every 28 days and fluorouracil 200 mg/m(2)/d given continuously over a 24-hour
period. RESULTS: Toxicity was recorded for 441 cycles. The scheme was well
tolerated: grade 1/2 nausea/vomiting occurred in 13 patients (15.6%), grade 1/2
diarrhea in nine (10.8%), and grade 2/3 stomatitis in six (7.2%). Three patients
(3.6%) experienced grade 3/4 leukopenia and four (4.8%) experienced grade 2/3
anemia. Grade 2/3 neurologic toxicity was observed in three cases (3.6%), and
grade 2/3 hand-foot syndrome was observed in three (3.6%). The median relative
dose-intensity was 92% and 100% for vinorelbine and fluorouracil, respectively.
Six patients (7.2%) attained a complete clinical response and 45 (54.2%) attained
a partial response, for an overall response rate of 61.4% (95% confidence
interval, 50.9% to 71.9%). Twenty-one patients (25.3%) obtained disease
stabilization, and 11 (13.3%) experienced disease progression. Median time to
progression in responding patients was 15 months; median overall survival of the
entire population was 22 months. CONCLUSION: Vinorelbine associated with
protracted infusional fluorouracil is an active and manageable scheme in advanced
breast cancer patients previously treated with anthracyclines. The response
obtained is durable.
PMID- 11013278
TI - Impact of neoadjuvant chemotherapy on postoperative morbidity in soft tissue
sarcomas.
AB - PURPOSE: The purpose of this study was to test the hypothesis that neoadjuvant
chemotherapy (NeoCT) does not increase morbidity in patients undergoing radical
surgery for soft tissue sarcomas. PATIENTS AND METHODS: The records of 309
patients who presented to The University of Texas M.D. Anderson Cancer Center for
definitive surgical management of primary soft tissue sarcomas were
retrospectively reviewed. One hundred five patients who received NeoCT were
compared with 204 patients who had surgery first (Surg). Patients had extremity
sarcomas (71 NeoCT patients and 130 Surg patients) or retroperitoneal/visceral
sarcomas (34 NeoCT and 74 Surg). RESULTS: NeoCT patients had larger tumors
(median, 12 v 8 cm), more frequently had high-grade tumors (90% v 64%), and were
younger (median age 47 v 55 years). The incidence of surgical complications was
not different for NeoCT patients than for Surg patients, both in those with
extremity sarcomas (34% v 41%) and in those with retroperitoneal/visceral
sarcomas (29% v 34%). The most common complications were wound infections and
other wound complications. Preoperative radiation therapy, autologous flap
coverage, and extremity tumors were associated with increased wound
complications. No significant differences in length of hospital stay, rate of
readmission, or rate of reoperation for complications were found between the
NeoCT and Surg groups. One of the three postoperative deaths in our series
occurred in the NeoCT group. CONCLUSION: In this retrospective review, there was
no evidence that NeoCT increased postoperative morbidity in patients with soft
tissue sarcomas. Prospective, randomized studies are needed to confirm these
results.
PMID- 11013279
TI - Eastern Cooperative Oncology Group Phase I trial of protracted venous infusion
fluorouracil plus weekly gemcitabine with concurrent radiation therapy in
patients with locally advanced pancreas cancer: a regimen with unexpected early
toxicity.
AB - PURPOSE: We performed a phase I trial of protracted venous infusion (PVI)
fluorouracil (5-FU) plus weekly gemcitabine with concurrent radiation therapy in
patients with locally advanced pancreas cancer to determine the maximum-tolerated
dose of gemcitabine that could be safely administered. We also sought to identify
the toxicities associated with this treatment protocol. PATIENTS AND METHODS:
Seven patients with locally advanced pancreas cancer were treated with planned
doses of radiation (59.4 Gy) and PVI of 5-FU (200 mg/m(2)/d) with gemcitabine
doses of 50 to 100 mg/m(2)/wk. RESULTS: Two of three patients at the 100
mg/m(2)/wk dose level experienced dose-limiting toxicity (DLT), as did three of
four at the 50-mg/m(2)/wk dose level. One patient experienced a mucocutaneous
reaction described as a Stevens-Johnson syndrome that was attributed to
chemotherapy. Three patients developed gastric or duodenal ulcers with severe
bleeding requiring transfusion. One patient developed severe thrombocytopenia
lasting longer than 4 weeks. Three of the five episodes of DLT developed at
radiation doses < or = 36 Gy. CONCLUSION: Based on this experience, we cannot
recommend further investigation of regimens incorporating gemcitabine into
regimens of radiation with PVI 5-FU. The mechanism of this synergistic toxicity
remains to be determined.
PMID- 11013280
TI - Phase III comparative study of high-dose cisplatin versus a combination of
paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.
AB - PURPOSE: New effective chemotherapy is needed to improve the outcome of patients
with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a
single agent or in combination with cisplatin has been shown to be a potentially
new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between
January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were
randomized to received either a control arm of high-dose cisplatin (100 mg/m(2))
or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80
mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was
a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate
for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time
to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin
arm, respectively (P=.026). The study, however, failed to show a significant
improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in
the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was
more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the
paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more
ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was
similar overall between the two arms. CONCLUSION: This large randomized phase III
trial failed to show a significant improvement in survival for the
paclitaxel/cisplatin combination compared with high-dose cisplatin in patients
with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a
better clinical response, resulting in an increased time to progression while
providing a similar QOL.
PMID- 11013281
TI - Treatment of brain metastases of small-cell lung cancer: comparing teniposide and
teniposide with whole-brain radiotherapy--a phase III study of the European
Organization for the Research and Treatment of Cancer Lung Cancer Cooperative
Group.
AB - PURPOSE: Approximately 60% of patients with small-cell lung cancer (SCLC) develop
brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement
in more than 50% of these patients. Because brain metastases are a sign of
systemic progression, and chemotherapy was found to be effective as well, it
becomes questionable whether WBRT is the only appropriate therapy in this
situation. PATIENTS AND METHODS: In a phase III study, SCLC patients with brain
metastases were randomized to receive teniposide with or without WBRT. Teniposide
120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10
fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy.
Response was measured clinically and by computed tomography of the brain.
RESULTS: One hundred twenty eligible patients were randomized. A 57% response
rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to
69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12%
to 34%) (P<.001). Time to progression in the brain was longer in the combined
modality group (P=.005). Clinical response and response outside the brain were
not different. The median survival time was 3.5 months in the combined-modality
arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups
was not different (P=.087). CONCLUSION: Adding WBRT to teniposide results in a
much higher response rate of brain metastases and in a longer time to progression
of brain metastases than teniposide alone. Survival was poor in both groups and
not significantly different.
PMID- 11013282
TI - Contribution of dexamethasone to control of chemotherapy-induced nausea and
vomiting: a meta-analysis of randomized evidence.
AB - PURPOSE: To synthesize the available randomized evidence on the efficacy of
dexamethasone when used for protection against acute and delayed nausea and
vomiting in patients receiving highly or moderately emetogenic cancer
chemotherapy. MATERIALS AND METHODS: A meta-analysis was performed using trials
identified through MEDLINE (1966 to April 1999), Embase, Derwent Drug File, and
the Cochrane Library's Database of Controlled Trials. Data on acute and delayed
emesis and nausea were collected. All randomized studies comparing dexamethasone
to placebo, no treatment, or other antiemetics qualified, including cross-over
trials providing first-cycle data. RESULTS: Of 1,200 citations screened, 32
studies with 42 pertinent comparisons and 5,613 patients were included in the
meta-analysis. Dexamethasone was superior to placebo or no treatment for complete
protection from acute emesis (odds ratio, 2.22; 95% confidence interval [CI],
1.89 to 2.60) and for complete protection from delayed emesis (odds ratio, 2.04;
95% CI, 1.63 to 2.56). The results were similar for complete protection from
nausea. The pooled risk difference for complete protection from emesis was 16%
for both the acute and delayed phases (95% CI, 13% to 19% and 11% to 20%,
respectively). The beneficial effect was similar in subgroups defined by various
study design parameters. No trial addressed the efficacy of dexamethasone in the
delayed phase without having administered dexamethasone for acute-phase
protection as well. CONCLUSION: Dexamethasone is clearly effective in protecting
from emesis both in the acute and delayed phases, with emesis avoided in one
patient out of six treated. Future trials should determine whether the delayed
phase effect is independent of the acute-phase benefit.
PMID- 11013284
TI - Unusual manifestations of acute leukemia. Case 1. CNS extramedullary relapse of
acute promyelocytic leukemia after arsenic trioxide-induced remission.
PMID- 11013283
TI - Phase I assessment of the pharmacokinetics, metabolism, and safety of emitefur in
patients with refractory solid tumors.
AB - PURPOSE: To determine the toxicities, dose-limiting toxicities (DLT), maximum
tolerated dose, and pharmacokinetic profile of emitefur (BOF-A2) in patients with
advanced solid tumors. METHODS: This was a phase I dose-escalating trial in which
cohorts of patients received BOF-A2 (cohort 1, 300 mg/m(2) orally [PO] tid;
cohort 2, 200 mg/m(2) PO tid; cohort 3, 200 mg/m(2) bid; and cohort 4, 250
mg/m(2) bid) for 14 consecutive days followed by 1 week of rest (cycle 1).
Pharmacokinetics, toxicity, and tumor response were monitored. RESULTS: Nineteen
patients received 110 cycles (three patients in cohort 1, three patients in
cohort 2, 10 patients in cohort 3, and three patients in cohort 4). DLT (grade 3
stomatitis, diarrhea, leukopenia) was observed in cohorts 1, 2, and 4.
Pharmacokinetics indicated that prolonged systemic expression of fluorouracil (5
FU) is maintained after administration of BOF-A2 at a dose of 200 mg bid for 14
days. The mean steady-state concentration of plasma 5-FU was > or = 24 ng/mL,
which was 184-fold greater than the minimum effective cytotoxic concentration in
vitro. Lack of variation of 5-FU trough levels within a day at steady-state
indicates suppression of circadian variation. One patient in cohort 3 achieved a
partial response and five patients maintained stable disease in excess of 6
months. CONCLUSION: BOF-A2 at a dose of 200 mg PO bid for 14 days followed by 7
days of rest is well tolerated. Prolonged exposure to 5-FU above the predicted
preclinical minimum effective concentration is maintained, without evidence of
circadian variation. Furthermore, evidence of antitumor activity is suggested.
PMID- 11013285
TI - Unusual manifestations of acute leukemia. Case 2. Leukemia and rash:
paraneoplastic or drug-induced?
PMID- 11013286
TI - Unusual manifestations of acute leukemia. Case 3. Unilateral leukemic hypopyon.
PMID- 11013287
TI - The art of oncology: when the tumor is not the target. Tell it like it is.
PMID- 11013288
TI - Myelodysplasia after autotransplantation.
PMID- 11013290
TI - Radiation therapy or surgery for base-of-tongue tumors?
PMID- 11013289
TI - Problematic WHO reclassification of myelodysplastic syndromes. Members of the
International MDS Study Group.
PMID- 11013291
TI - Paclitaxel for limited-stage small-cell lung cancer.
PMID- 11013292
TI - Thalidomide in the treatment of high-grade gliomas.
PMID- 11013293
TI - Prophylactic surgery: oophorectomy or adnexectomy?
PMID- 11013294
TI - Stage shift and complementary/alternative medicine.
PMID- 11013295
TI - Urinary alpha-tocopherol metabolites in alpha-tocopherol transfer protein
deficient patients.
AB - Patients with alpha-tocopherol transfer protein (alpha-TTP) defects experience
neurological symptoms characteristic of vitamin E deficiency and depend on
continuous high alpha-tocopherol supplements. We investigated the excretion of
2,5,7, 8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC), a urinary
metabolite of alpha-tocopherol, as a putative marker for the alpha-tocopherol
status of alpha-TTP-deficient patients and control subjects. In three patients
vitamin E supplementation was stopped for short periods of time, during which
plasma alpha-tocopherol concentrations and urinary alpha-CEHC excretion were
measured. In the patients, plasma alpha-tocopherol decreased below normal (<5
micromol/l) but alpha-CEHC excretion remained above the range of unsupplemented
control subjects (0.118-0.306 mg/day, n = 6). In healthy subjects, however, alpha
CEHC excretion was increased only after surpassing a plasma alpha-tocopherol
threshold of 30-40 micromol/l. Such a threshold did not exist in patients. The
general mechanism of alpha-tocopherol degradation did not appear to differ
between patients and control subjects. The presumed mechanism of omega- and
subsequent beta-oxidation was supported by the detection of alpha- CPHC, an alpha
-CEHC homolog with a side chain longer by 3 carbon atoms, both in supplemented
patients and in control subjects.
PMID- 11013297
TI - Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5beta
cholestane-3alpha,7alpha,12alpha,24,25-pentol, in human urine.
AB - The stereochemistry at C-24 and C-25 of 27-nor-5beta-cholestane
3alpha,7alpha,12alpha,24 ,25-pentol, a principal bile alcohol in human urine, and
its biosynthesis are studied. Four stereoisomers of the C(26)-24,25-pentols were
synthesized by reduction with LiAlH(4) of the corresponding epoxides prepared
from (24S)- or (24R)-27-nor-5beta-cholest-25-ene-3alpha, 7alpha,12alpha,24
tetrol. The stereochemistries at C-25 were deduced by comparison of the C(26)
24,25-pentols with the oxidation products of (24Z)-27-nor-5beta-cholest-24-ene
3alpha,7alpha, 12alpha-triol with osmium tetraoxide. On the basis of this
assignment, the principal bile alcohol excreted into human and rat urine was
determined to be (24S,25R)-27-nor-5beta-cholestane-3alpha,7alpha, 12alpha,24,25
pentol, accompanied by a lesser amount of (24R, 25R)-isomer. To elucidate the
biosynthesis of the C(26)-24,25-pentol, a putative intermediate, 3alpha,7alpha,
12alpha-trihydroxy-27-nor-5beta-cholestan-24-one, derived from 3alpha,7alpha,
12alpha-trihydroxy-24-oxo-5beta-cholestanoic acid by decarboxylation during the
side-chain oxidation of 3alpha,7alpha, 12alpha-trihydroxy-5beta-cholestanoic
acid, was incubated with rat liver homogenates. The 24-oxo-bile alcohol could be
efficiently reduced to yield mainly (24R)-27-nor-5beta-cholestane-3alpha,7alpha,
12alpha,24-tetrol. If a 25R-hydroxylation of the latter steroid occurs, it should
lead to formation of (24S,25R)-C(26)-24,25-pentol. Now it has appeared that a
major bile alcohol excreted into human urine is (24S,25R)-27-nor-5beta-cholestane
3alpha,7alpha, 12alpha, 24, 25-pentol, which might be derived from 3alpha,7alpha,
12alpha-trihydroxy-27-nor-5beta-cholestan-24-one via (24R)-27-nor-5beta
cholestane-3alpha, 7alpha,12alpha,24-tetrol.
PMID- 11013296
TI - Age-related decrease of dehydroepiandrosterone concentrations in low density
lipoproteins and its role in the susceptibility of low density lipoproteins to
lipid peroxidation.
AB - The incidence of atherosclerosis and related diseases increases with age. The
aging process may enhance lipoprotein modification, which leads to an increase in
the susceptibility of low density lipoprotein (LDL) and high density lipoprotein
(HDL) to oxidation. Dehydroepiandrosterone (DHEA), the most abundant steroid
hormone in humans, has been shown to have antiatherogenic effects. This hormone
also decreases dramatically with age. In the present study, we were interested in
determining the presence of DHEA/DHEAS (dehydroepiandrosterone sulfate) and
changes in their concentrations in HDL and LDL lipoproteins with age. Moreover,
we studied the susceptibility of LDL to oxidation with age in the presence or
absence of vitamin E or DHEA. We demonstrated that vitamin E is unable to restore
the decreased resistance to oxidation of LDL from elderly subjects to that of LDL
obtained from young subjects. Furthermore, our results provide evidence that DHEA
is an integral part of LDL and HDL and disappears to almost nondetectable levels
during aging. The DHEA incorporated into the LDL from elderly subjects increased
LDL resistance to oxidation in a concentration-dependent manner. The increased
resistance provided by DHEA was higher than that with vitamin E. DHEA seems to
act either by protecting vitamin E from disappearance from LDL under oxidation or
by scavenging directly the free radicals produced during the oxidative process.
Our results suggests that DHEA exerts an antioxidative effect on LDL, which could
have antiatherogenic consequences. Careful clinical trials of DHEA replacement
should determine whether this ex vivo effect could be translated into any
measurable antiatherogenic (cardioprotective) action.
PMID- 11013298
TI - Polymorphism of class A scavenger receptors in C57BL/6 mice.
AB - Scavenger receptors class A (SR-A) have been hypothesized to regulate the
development of atherosclerotic lesions through recognition of modified low
density lipoprotein (LDL) and macrophage adhesion to substrata. Supporting data
have been collected from studies using the monoclonal antibody 2F8, an antibody
developed from the BALB/c strain-derived macrophage cell line, RAW.264. Although
2F8 immunostained both cultured peritoneal macrophages (MPM) and thymic
macrophages from Swiss, BALB/c, and DBA/2 mice, no immunostaining was detected in
cells and tissues from C57BL/6 mice, one of the most commonly used
atherosclerosis-susceptible mouse strains. Similarly, 2F8 detected SR-A protein
in MPM by Western blotting in all strains except C57BL/6. However, a guinea pig
antiserum developed to a fusion protein of the extracellular SR-A domain detected
appropriately sized bands in all strains. Incubation with 2F8 antagonized
acetylated low-density lipoprotein (AcLDL)-induced cholesterol esterification in
MPM from BALB/c, Swiss, and DBA/2 strains but had no effect on MPM from C57BL/6
mice. Sequencing of SR-A cDNA from C57BL/6 mice demonstrated complete identity
with published sequence in the collagen-like domain. However, four single-residue
substitutions were noted in the alpha-helical coiled-coil domain. Site-directed
mutagenesis demonstrated that a single substitution (L168S) in this domain
accounted for the loss of 2F8 immunoreactivity. Differing reactivities toward a
commonly used monoclonal antibody were used to identify polymorphism of SR-A in
C57BL/6 mice.
PMID- 11013299
TI - Characterization of the basis of lipoprotein [a] lysine-binding heterogeneity.
AB - Although elevated plasma concentrations of lipoprotein [a] (Lp[a]) are considered
to be a risk factor for atherosclerosis, the mechanisms by which Lp[a] mediates
its pathogenic effects have not been conclusively determined. The apolipoprotein
[a] (apo[a]) component of Lp[a] confers unique structural properties to this
lipoprotein, including the ability to bind to lysine residues in biological
substrates. It has been shown, however, that only a fraction of plasma Lp[a]
(Lp[a]-Lys(+)) binds to lysine-Sepharose in vitro. The nature of the non-lysine
binding Lp[a] fraction in plasma (Lp[a]-Lys(-)) is currently unknown. In the
present study, the Lp[a]-Lys(+) fraction was determined in the plasma of six
unrelated individuals; the Lp[a]-Lys(+) fraction in these plasma samples ranged
from approximately 37 to approximately 48%. Interestingly, purification of the
Lp[a] by density gradient ultracentrifugation followed by gel filtration and ion
exchange chromatography resulted in progressive increases in the Lp[a]-Lys(+)
fraction. Addition of either purified low density lipoprotein (LDL) or
fibronectin to the purified Lp[a] at a 1:1 molar ratio reduced the Lp[a]-Lys(+)
fraction (maximal decrease of 34 and 20%, respectively) whereas addition of both
fibronectin and LDL to the purified Lp[a] resulted in a further decrease (45%
maximally) in this fraction. Similar results were obtained by using a recombinant
expression system for apo[a]: addition of a 4-fold molar excess of either LDL or
fibronectin to conditioned medium containing metabolically labeled recombinant
apo[a] reduced the Lys(+) fraction by 49 and 23%, respectively. Taken together,
our data suggest that the lysine-binding heterogeneity of plasma Lp[a] is not
primarily an intrinsic property of the lipoprotein, but rather results in large
part from its ability to noncovalently associate with abundant plasma components
such as LDL and fibronectin. These interactions appear to mask the lysine-binding
site in apo[a] kringle IV type 10, which mediates the interaction of Lp[a] with
lysine-Sepharose. The contribution of these interactions to the function of Lp[a]
in vivo remains to be investigated.
PMID- 11013300
TI - Electrospray ionization mass spectrometry analyses of nuclear membrane
phospholipid loss after reperfusion of ischemic myocardium.
AB - The role of nuclear membrane phospholipids as targets of phospholipases resulting
in the generation of nuclear signaling messengers has received attention. In the
present study, we have exploited the utility of electrospray ionization mass
spectrometry to determine the phospholipid content of nuclei isolated from
perfused hearts. Rat heart nuclei contained choline glycerophospholipids composed
of palmitoyl and stearoyl residues at the sn-1 position with oleoyl, linoleoyl,
and arachidonoyl residues at the sn-2 position. Diacyl molecular species were the
predominant molecular subclass in the choline glycerophospholipids, with the
balance of the molecular species being plasmalogens. In the ethanolamine
glycerophospholipid pool from rat heart nuclei approximately 50% of the molecular
species were plasmalogens, which were enriched with arachidonic acid at the sn-2
position. A 50% loss of myocytic nuclear choline and ethanolamine
glycerophospholipids was observed in hearts rendered globally ischemic for 15 min
followed by 90 min of reperfusion in comparisons with the content of these
phospholipids in control perfused hearts. The loss of nuclear choline and
ethanolamine glycerophospholipids during reperfusion of ischemic myocardium was
partially reversed by the calcium-independent phospholipase A(2) (iPLA(2))
inhibitor bromoenol lactone (BEL), suggesting that the loss of nuclear
phospholipids during ischemia/reperfusion is mediated, in part, by iPLA(2).
Western blot analyses of isolated nuclei from ischemic hearts demonstrated that
iPLA(2) is translocated to the nucleus after myocardial ischemia. Taken
toghether, these studies have demonstrated that nuclear phospholipid mass
decreases after myocardial ischemia by a mechanism that involves, at least in
part, phospholipolysis mediated by iPLA2.
PMID- 11013301
TI - Acute effects of low density lipoprotein apheresis on metabolic parameters of
apolipoprotein B.
AB - Apheresis is a treatment option for patients with severe hypercholesterolemia and
coronary artery disease. It is unknown whether such therapy changes kinetic
parameters of lipoprotein metabolism, such as apolipoprotein B (apoB) secretion
rates, conversion rates, and fractional catabolic rates (FCR). We studied the
acute effect of apheresis on metabolic parameters of apoB in five patients with
drug-resistant hyperlipoproteinemia, using endogenous labeling with D(3)-leucine,
mass spectrometry, and multicompartmental modeling. Patients were studied prior
to and immediately after apheresis therapy. The two tracer studies were modeled
simultaneously, taking into account the non-steady-state concentrations of apoB.
The low density lipoprotein (LDL)-apoB concentration was 120+/-32 mg dl(-1) prior
to and 52+/-18 mg dl(-1) immediately after apheresis therapy. The metabolic
studies indicate that no change in apoB secretion (13.9+/- 4.9 mg kg(-1) day(-1))
is required to fit the tracer and apoB mass data obtained before and after
apheresis and that in four of the five patients the LDL-apoB FCR (0.21+/-0.02
day(-1)) was not altered after apheresis. In one subject the LDL-apoB FCR
temporarily increased from 0.22 day(-1) to 0.35 day(-1) after apheresis. The
conversion rate of very low density lipoprotein (VLDL)-apoB to LDL-apoB is
temporarily decreased from 76 to 51% after apheresis and thus less LDL-apoB is
produced after apheresis. We conclude that an acute reduction of LDL-apoB
concentration does not affect apoB secretion or LDL-apoB FCR, but that apoB
conversion to LDL is temporarily decreased. Thus, in most patients the decreased
rate of delivery of neutral lipids or apoB to the liver does not result in an
upregulation of LDL receptors or in decreased apoB secretion.
PMID- 11013302
TI - Inhibition of cholesteryl ester transfer protein by substituted
dithiobisnicotinic acid dimethyl ester: involvement Of a critical cysteine.
AB - SC-71952, a substituted analog of dithiobisnicotinic acid dimethyl ester, was
identified as a potent inhibitor of cholesteryl ester transfer protein (CETP).
When tested in an in vitro assay, the concentration of SC-71952 required for half
maximal inhibition was 1 microm. The potency of SC-71952 was enhanced 200-fold by
preincubation of the inhibitor with CETP, and was decreased 50-fold by treatment
with dithiothreitol. Analogs of SC-71952 that did not contain a disulfide linkage
were less potent, did not display time dependency, and were not affected by
dithiothreitol treatment. Kinetic and biochemical characterization of the
inhibitory process of CETP by SC-71952 suggested that the inhibitor initially
binds rapidly and reversibly to a hydrophobic site on CETP. With time, the bound
inhibitor irreversibly inactivates CETP, presumably by reacting with one of the
free cysteines of CETP. Liquid chromatography/mass spectroscopy (LC/MS) analyses
of tryptic digests of untreated or SC-71952-inactivated CETP was used to identify
which cysteine(s) were potentially involved in the time-dependent, irreversible
component of inactivation by the inhibitor. One disulfide bond, Cys143-Cys184,
was unaffected by treatment with the inhibitor. Inactivation of CETP by SC-71952
correlated with a progressive decrease in the abundance of free Cys-13 and Cys
333. Conversion of Cys-13 to alanine had no effect on the rapid reversible
component of inactivation by SC-71952. However, it abolished the time-dependent
enhancement in potency seen with the inhibitor when using wild-type CETP. These
data indicate that Cys-13 is critical for the irreversible inactivation of CETP
by SC-71952 and provides support for the structural model that places Cys-13 near
the neutral lipid-binding site of CETP.
PMID- 11013303
TI - Identification of genes specifically expressed in the accumulated visceral
adipose tissue of OLETF rats.
AB - The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2
diabetes, characterized by abdominal obesity, insulin resistance, hypertension,
and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and
its related complications, we used representational difference analysis and
identified the genes more abundantly and specifically expressed in the visceral
adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant
counterpart, that is, Long-Evans Tokushima Otsuka (LETO) rats. By Northern blot
analysis, we confirmed the differential expression of 13 genes, including 3 novel
genes. The upregulated expression of well-characterized lipid metabolic enzymes,
such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol
esterase, were observed in VAT of OLETF rats. We demonstrated the differential
expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1
and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the
secreted proteins revealed exclusive mRNA expression and they were not detected
in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also
expressed specifically in VAT of OLETF rats and were absent in that of LETO rats
and other tissues, including subdermal and brown adipose tissues. The C-terminal
partial amino acid sequence of OL-64 revealed that it showed approximately 40%
homology with alpha(1)-antitrypsin and it seemed to be a new member of the serine
proteinase inhibitor (SERPIN) gene family. VAT of OLEFT rats had a unique gene
expression profile, and the accumulated VAT-specific known and novel secreted
proteins may play a role(s) in the pathogenesis of obesity and its related
complications.
PMID- 11013304
TI - Apolipoprotein A4-1/2 polymorphism and response of serum lipids to dietary
cholesterol in humans.
AB - The response of serum lipids to dietary changes is to some extent an innate
characteristic. One candidate genetic factor that may affect the response of
serum lipids to a change in cholesterol intake is variation in the apolipoprotein
A4 gene, known as the APOA4-1/2 or apoA-IVGln360His polymorphism. However,
previous studies showed inconsistent results. We therefore fed 10 men and 23
women with the APOA4-1/1 genotype and 4 men and 13 women with the APOA4-1/2 or
2/2 genotype (carriers of the APOA4-2 allele) two diets high in saturated fat,
one containing cholesterol at 12.4 mg/MJ, 136.4 mg/day, and one containing
cholesterol at 86.2 mg/MJ, 948.2 mg/day. Each diet was supplied for 29 days in
crossover design. The mean response of serum low density lipoprotein cholesterol
was 0.44 mmol/l (17 mg/dl) in both subjects with the APOA4-1/1 genotype and in
subjects with the APOA4-2 allele [95% confidence interval of difference in
response, -0.20 to 0.19 mmol/l (-8 to 7 mg/dl)]. The mean response of high
density lipoprotein cholesterol was also similar, 0.10 mmol/l (4 mg/dl), in the
two APOA-4 genotype groups [95% confidence interval of difference in response,
0.07 to 0.08 mmol/l (-3 to 3 mg/dl)]. Thus, the APOA4-1/2 polymorphism did not
affect the response of serum lipids to a change in the intake of cholesterol in
this group of healthy Dutch subjects who consumed a background diet high in
saturated fat. Knowledge of the APOA4-1/2 polymorphism is probably not a
generally applicable tool for the identification of subjects who respond to a
change in cholesterol intake.
PMID- 11013306
TI - Influence of phospholipid depletion on the size, structure, and remodeling of
reconstituted high density lipoproteins.
AB - This study shows that phospholipid depletion has a major impact on the size and
structure of spherical, reconstituted high density lipoproteins (rHDL) and their
remodeling by cholesteryl ester transfer protein (CETP). Spherical rHDL, 9.2 nm
in diameter with a phospholipid/cholesteryl ester/unesterified
cholesterol/apolipoprotein A-I (apoA-I) (PL/CE/UC/A-I) molar ratio of
37.3/24.5/4.1/1.0, were depleted progressively of phospholipids by incubation
with phospholipase A(2). After 30 min of incubation the PL/CE/UC/A-I molar ratio
of the rHDL was 8.0/31.2/4.4/1.0 and their diameter had decreased to 8.0 nm.
Comparable changes in rHDL size and composition were also apparent when the
incubations were carried out in the presence of other lipoprotein classes and
lipoprotein-deficient plasma. The changes in size and composition were not
accompanied by the dissociation of apoA-I from the rHDL. Phospholipid depletion
did not affect rHDL surface charge or the structure and stability of apoA-I. The
remodeling of unmodified and phospholipid-depleted rHDL by CETP was also
investigated. When the rHDL were incubated for 3 h with CETP and Intralipid,
transfers of core lipids between the phospholipid-depleted rHDL and Intralipid
were decreased relative to unmodified rHDL. This difference was no longer
apparent when the incubations were extended beyond 3 h. In these incubations apoA
I dissociated from the phospholipid-depleted and unmodified rHDL at 3 and 12 h,
respectively. At 24 h the respective diameters of the unmodified rHDL and
phospholipid-depleted rHDL were 8.0 and 7.8 nm. In conclusion, phospholipid
depletion has a major impact on rHDL size and their remodeling by CETP.
PMID- 11013305
TI - 24-hydroxycholesterol is a substrate for hepatic cholesterol 7alpha-hydroxylase
(CYP7A).
AB - (24S)-Hydroxycholesterol is formed from cholesterol in the brain and is important
for cholesterol homeostasis in this organ. Elimination of (24S)
hydroxycholesterol has been suggested to occur in the liver but little is known
about the metabolism of this oxysterol. In the present investigation, we report
formation of 7alpha, 24-dihydroxycholesterol in pig and human liver. 7alpha
hydroxylase activity toward both isomers of 24-hydroxycholesterol [(24S) and
(24R)] was found in a partially purified and reconstituted cholesterol 7alpha
hydroxylase (CYP7A) enzyme fraction from pig liver microsomes. In contrast, a
purified enzyme fraction of pig liver oxysterol 7alpha-hydroxylase with high
activity toward 27-hydroxycholesterol did not show any detectable activity toward
24-hydroxycholesterol. 7alpha-Hydroxylation of 24-hydroxycholesterol was strongly
inhibited by 7-oxocholesterol, a known inhibitor of CYP7A. Human CYP7A,
recombinantly expressed in Escherichia coli and in simian COS cells, showed
7alpha-hydroxylase activity toward both cholesterol and the two isomers of 24
hydroxycholesterol, with a preference for the (24S)-isomer. Our results show that
24-hydroxycholesterol is metabolized by CYP7A, an enzyme previously considered to
be specific for cholesterol and cholestanol and not active toward oxysterols.
Because CYP7A is the rate-limiting enzyme in the major pathway of bile acid
biosynthesis, the possibility is discussed that at least part of the 24
hydroxycholesterol is converted into 7alpha-hydroxylated bile acids by the
enzymes involved in the normal biosynthesis of bile acids.
PMID- 11013307
TI - Distribution of phospholipid transfer protein in human plasma: presence of two
forms of phospholipid transfer protein, one catalytically active and the other
inactive.
AB - Plasma phospholipid transfer protein (PLTP) plays an important role in the
maintenance of plasma high-density lipoprotein (HDL) content and remodeling of
HDL in the circulation. In the present study we have used different fractionation
methods to investigate the distribution of PLTP in human plasma. A novel enzyme
linked immunosorbent assay developed during the study allowed for simultaneous
assessment of both PLTP mass and activity in the fractions obtained. Size
exclusion chromatography and plasma fractionation by nondenaturing polyacrylamide
gel electrophoresis (PAGE) yielded similar results demonstrating that PLTP
associates in native plasma with two distinct particle populations, while
ultracentrifugation with high salt leads to detachment of PLTP from lipoprotein
particles and loss of a majority of its phospholipid transfer activity.
Interestingly, analysis of the size-exclusion chromatography fractions
demonstrated that PLTP exists in the circulation as an active population that
elutes in the position of HDL corresponding to an average molecular mass of 160+/
40 kDa and an inactive form with an average mass of 520+/-120 kDa. The inactive
fraction containing approximately 70% of the total PLTP protein eluted between
HDL and low density lipoprotein (LDL). Thus, the two PLTP pools are associated
with different types of lipoprotein particles, suggesting that the PLTP activity
in circulation is modulated by the plasma lipoprotein profile and lipid
composition.
PMID- 11013308
TI - Cholesterol delivered to macrophages by oxidized low density lipoprotein is
sequestered in lysosomes and fails to efflux normally.
AB - Oxidized low density lipoprotein (LDL) has been found to exhibit numerous
potentially atherogenic properties, including transformation of macrophages to
foam cells. It is believed that high density lipoprotein (HDL) protects against
atherosclerosis by removing excess cholesterol from cells of the artery wall,
thereby retarding lipid accumulation by macrophages. In the present study, the
relative rates of HDL-mediated cholesterol efflux were measured in murine
resident peritoneal macrophages that had been loaded with acetylated LDL or
oxidized LDL. Total cholesterol content of macrophages incubated for 24 h with
either oxidized LDL or acetylated LDL was increased by 3-fold. However, there was
no release of cholesterol to HDL from cells loaded with oxidized LDL under
conditions in which cells loaded with acetylated LDL released about one-third of
their total cholesterol to HDL. Even mild degrees of oxidation were associated
with impairment of cholesterol efflux. Macrophages incubated with vortex
aggregated LDL also displayed impaired cholesterol efflux, but aggregation could
not account for the entire effect of oxidized LDL. Resistance of apolipoprotein B
(apoB) in oxidized LDL to lysosomal hydrolases and inactivation of hydrolases by
aldehydes in oxidized LDL were also implicated. The subcellular distribution of
cholesterol in oxidized LDL-loaded cells and acetylated LDL-loaded cells was
investigated by density gradient fractionation, and this indicated that
cholesterol derived from oxidized LDL accumulates within lysosomes. Thus
impairment of cholesterol efflux in oxidized LDL-loaded macrophages appears to be
due to lysosomal accumulation of oxidized LDL rather than to impaired transport
of cholesterol from a cytosolic compartment to the plasma membrane.
PMID- 11013309
TI - Increased low density lipoprotein degradation in aorta of irradiated mice is
inhibited by preenrichment of low density lipoprotein with alpha-tocopherol.
AB - We previously reported that upper thoracic exposure to ionizing radiation (IR)
accelerates fatty streak formation in C57BL/6 mice and that such effects are
inhibited by overexpression of the antioxidant enzyme CuZn-superoxide dismutase
(SOD). Notably, IR-accelerated lesion formation is strictly dependent on a high
fat diet (i.e., atherogenic lipoproteins) but does not involve alterations in
circulating lipid or lipoprotein levels. We thus proposed that IR promotes
changes in the artery wall that enhance the deposition of lipoprotein lipids. To
address this hypothesis, we examined the effects of IR on aortic accumulation and
degradation of low density lipoproteins (LDL). Ten-week-old C57BL/6 mice were
exposed to a single (8-Gy) dose of (60)Co radiation to the upper thoracic area or
were sham irradiated (controls) and were then placed on the high fat diet. Five
days postexposure, the mice received either (125)I-labeled LDL ((125)I-LDL)
(which was used to measure intact LDL) or (125)I-labeled tyramine cellobiose
((125)I-TC)-LDL (which was used to measure both intact and cell-degraded LDL) via
tail vein injection. On the basis of trichloroacetic acid (TCA)-precipitable
counts in retroorbital blood samples, > or =95% of donor LDL was cleared within
24 h and there were no differences in time-averaged plasma concentrations of the
two forms of LDL among irradiated and control mice. Aortic values increased
markedly within the first hour and thereafter exhibited a slow increase up to 24
h. There were no differences between irradiated and control mice at 1 h, when
values primarily reflected LDL entry, but a divergence was observed thereafter.
At 24 h, (125)I-TC-associated counts were 1.8-fold higher in irradiated mice (P =
0.10). In contrast, (125)I-LDL-associated counts were 30% lower in irradiated
mice (P< 0.05), suggesting that most of the retained (125)I-TC was associated
with LDL degradation products. Consistent with the proposed involvement of
oxidative or redox-regulated events, IR-induced LDL degradation was lower in SOD
transgenic than wild-type mice (P<0.05). The importance of LDL oxidation was
suggested by observations that IR-induced LDL degradation was significantly
reduced by preenriching LDL with alpha-tocopherol. On the basis of these results,
we propose that IR elicits SOD-inhibitable changes in the artery wall that
enhance LDL oxidation and degradation leading to the deposition of LDL-borne
lipids. These studies provide additional support for the role of oxidation in
lipoprotein lipid deposition and atherogenesis and suggest that IR promotes an
arterial environment that stimulates this process in vivo.
PMID- 11013310
TI - Hepatic apolipoprotein E expression promotes very low density lipoprotein
apolipoprotein B production in vivo in mice.
AB - In addition to its role in the uptake of apolipoprotein B (apoB)-containing
lipoproteins, apoE promotes hepatic very low density lipoprotein-triglyceride
(VLDL-TG) production in animal models. However, it is not known if apoE increases
the amount of TG per VLDL particle or the number of VLDL particles secreted. VLDL
apoB production is a measure of the rate of VLDL particle secretion. We
determined the effects of apoE deficiency and apoE overexpression on VLDL-apoB
production in mice. [(35)S]methionine was injected into endogenously label VLDL
apoB and Triton WR-1339 was simultaneously injected to block the catabolism of
VLDL. Compared with wild-type mice, the VLDL-apoB production rate was decreased
by 33% in apoE-deficient mice. Conversely, VLDL-apoB production was increased by
48% in mice overexpressing apoE compared with controls. Nascent VLDL, obtained
from post-Triton plasma, had a decreased, not increased, content of TG per apoB
in the apoE-overexpressing group compared with the control group. This study
demonstrates that hepatic apoE expression increases the output of VLDL
triglyceride by increasing the production rate of VLDL-apoB, suggesting that
hepatic apoE influences the number of VLDL particles secreted by the liver.
PMID- 11013311
TI - Sphingolipids and cholesterol modulate membrane susceptibility to cytosolic
phospholipase A(2).
AB - Modulation of cytosolic phospholipase A(2) (cPLA(2)) activity by sphingomyelin
(SPH), ceramide (Cer), and cholesterol (Chol) was investigated in CHO-2B cells
activated by the calcium ionophore A23187 and epinephrine. Chol depletion of CHO
2B cells by treatment with methyl-beta-cyclodextrin (5 mm) resulted in the
inhibition of the release of arachidonic acid whereas the restoration of the
level by Chol-loaded cyclodextrin relieved inhibition. Conversion of CHO-2B
cellular SPH to Cer by Staphylococcus aureus sphingomyelinase enhanced endogenous
cPLA(2) activation as well as uptake by cells of C2- and C6-ceramide analogs.
These results were confirmed in vitro with purified human recombinant cPLA(2)
acting on a model phospholipid substrate. The enzyme activity was inhibited by
SPH but reactivated by Cer as well as by Chol added to glycerophospholipid
liposomal substrates containing SPH. The results of this study, which combine in
situ and in vivo experimental approaches, indicate that membrane microdomains
enriched in SPH and Chol play a role in the modulation of the activity of cPLA2
and in arachidonic acid-derived mediator production.
PMID- 11013312
TI - Eicosanoids as endogenous regulators of leptin release and lipolysis by mouse
adipose tissue in primary culture.
AB - Prostaglandin E(2) (PGE(2)) stimulated leptin release over a 24-h incubation of
mouse adipose tissue in primary culture. The maximal stimulation of leptin
release was seen with 100 nm PGE(2). The role of endogenous eicosanoids in the
regulation of lipolysis and leptin formation was examined in the presence of NS
398, a selective cyclooxygenase-2 inhibitor. NS-398 at a concentration of 5
microm enhanced lipolysis by 30% and lowered leptin release by 24%. This
concentration of NS-398 almost completely inhibited PGE(2) formation. An
inhibition of basal lipolysis by PGE(2) or N(6)-cyclopentyladenosine (CPA) was
seen in the presence but not in the absence of NS-398. CPA, whose receptor, like
that of PGE(2) inhibits cyclic AMP accumulation in adipose tissue, also enhanced
leptin release. These data indicate that PGE2 can stimulate leptin release and
suggest that endogenous eicosanoids affect both lipolysis and leptin formation by
mouse adipose tissue.
PMID- 11013313
TI - International symposium on basic aspects of HDL metabolism and disease
prevention.
PMID- 11013314
TI - Taking issue: pharmacological progress: seeking balance.
PMID- 11013316
TI - Datapoints: Effects of changing from five to ten preauthorized outpatient
sessions.
PMID- 11013317
TI - Law & psychiatry: Pegram v. Herdrich: the Supreme Court passes the buck on
managed care.
PMID- 11013318
TI - Personal accounts. Managed care wars: a first casualty.
PMID- 11013319
TI - Managed care: Public-sector managed behavioral health care: VI. The Iowa approach
to profit and community reinvestment.
PMID- 11013321
TI - Economic grand rounds: Prevalence and cost of treating mental disorders among
elderly recipients of Medicare services.
PMID- 11013322
TI - Clozapine treatment of outpatients with schizophrenia: outcome and long-term
response patterns. 1993.
PMID- 11013323
TI - Drugs of the psychopharmacological revolution in clinical psychiatry.
PMID- 11013325
TI - Client-case manager racial matching in a program for homeless persons with
serious mental illness.
AB - OBJECTIVE: This study evaluated the relationship between client-case manager
racial matching and both service use and clinical outcomes in a case management
program for homeless persons with serious mental illness. METHODS: The study
focused on 1,785 clients from the first cohorts that entered the Center for
Mental Health Services' Access to Community Care and Effective Services and
Supports (ACCESS) program, a five-year demonstration program for homeless persons
with mental illness established at 18 sites between 1994 and 1996. A series of
two-way analyses of variance was used to assess the effect of client and case
manager race and their interaction on changes in outcomes and service use over a
12-month period. RESULTS: Although African Americans had more severe problems on
several measures and higher levels of service use at baseline, no differences in
service use at 12 months or in the changes in client outcomes as measured by nine
variables were associated with the different pairings of African-American and
white clients and case managers. White clients had a greater reduction in
psychotic symptoms than did African-American clients, regardless of client- case
manager racial pairing. No differences were found between white and African
American clients on the amount of services received over time. CONCLUSIONS: This
study found virtually no evidence of a relationship between client race, case
manager race, or client-case manager racial matching on either outcomes or
service use.
PMID- 11013324
TI - Racial differences in the prevalence of dementia among patients admitted to
nursing homes.
AB - OBJECTIVE: The purpose of this study was to determine the prevalence of dementia
among black and white residents on admission to nursing homes and to determine
whether demographic and health characteristics known to be associated with
dementia were correlated with dementia in this population. METHODS: Data from
medical records and structured interviews with family members, nursing staff, and
nursing home residents were gathered for 2,285 persons newly admitted to nursing
homes in Maryland from 1992 to 1995. A stratified sample of 59 nursing homes was
used. An expert panel of five physicians classified each resident as demented,
nondemented, or indeterminate. Associations between dementia status, race, and
selected characteristics were examined. RESULTS: Black residents (77 percent)
were significantly more likely than white residents (57 percent) to be classified
as demented. Older age was associated with dementia in both races. Less
education, male gender, and a history of a cerebrovascular accident were
associated with an increased prevalence of dementia among white residents only.
After demographic and health characteristics associated with dementia were
controlled for, black race remained independently associated with a diagnosis of
dementia. CONCLUSIONS: The rate of dementia on admission to nursing homes was
higher among black residents than among white residents, a finding that has
implications for the delivery of care. The higher rate may be due to psychosocial
factors operating differently in blacks and whites that influence the timing of
admission to a nursing home.
PMID- 11013326
TI - A managed behavioral health organization operated by an academic psychiatry
department.
AB - As a means of adapting to managed care, the psychiatry department at Wake Forest
University developed a managed behavioral health organization (MBHO) to manage
the care of enrollees in QualChoice, the health maintenance organization of the
Wake Forest University Baptist Medical Center. Before the academic MBHO was
created, care was managed by a for-profit MBHO. In this case study, financial and
utilization data were obtained from both MBHOs and from QualChoice. The data
confirm that the academic MBHO was able to offer competitive rates for its
services. It also was able to increase enrollees' use of the medical center's own
providers and facilities by making more referrals than were made by the for
profit MBHO. Developing a managed behavioral health organization can allow
academic psychiatry departments, either individually or as consortia, to preserve
the patient base they require for teaching, research, and financial stability.
PMID- 11013327
TI - Admissions, length of stay, and medication use among women in an acute care state
psychiatric facility.
AB - OBJECTIVE: Despite growing numbers of elderly persons with serious mental illness
such as schizophrenia, little research has been conducted on the manifestation of
serious mental illness in later life, and our understanding of the mental health
care needs of this population is limited. This study examined length of stay and
medication use among women age 50 and older admitted to an acute care state
psychiatric facility. METHODS: A computerized record search for all women
discharged from a large urban state psychiatric facility over a one-year period
was undertaken. Demographic and resource utilization data, including total length
of stay and pharmacy utilization, were obtained from the hospital database.
RESULTS: The database search produced the records of 564 women, with a mean age
of 37.5 years. Women constituted 60 percent of patients over age 50. The mean
length of stay was 16.1 days for the entire group; for women under age 50
(N=492), mean length of stay was 15 days, and for women age 50 and older (N=72),
it was 23.1 days (p=. 01). Among those age 50 and older, 58.3 percent had a
diagnosis of schizophrenia or schizoaffective disorder, compared with only 38
percent of those under age 50. CONCLUSIONS: Our data suggest that women
constitute the majority of patients over age 50 in a state psychiatric facility
and that they have longer stays than younger women.
PMID- 11013328
TI - Bed closures and incarceration rates among users of Veterans Affairs mental
health services.
AB - OBJECTIVE: This study examined incarceration rates of users of Department of
Veterans Affairs (VA) mental health services in 16 northeastern New York State
counties between 1994 and 1997-a time of extensive bed closures in the VA system
to determine whether incarceration rates changed during this period. METHODS:
Data were obtained for male patients who used inpatient and outpatient VA mental
health services between 1994 and 1997 and for men incarcerated in local jails
during this period. For comparison, services use and incarceration data were
obtained for all men who received inpatient behavioral health care at community
general hospitals and state mental hospitals between 1994 and 1996 in the same
counties. Probabilistic population estimation, a novel statistical technique, was
employed to evaluate the degree of overlap between clinical and incarceration
populations without relying on person-specific identifiers. RESULTS: Of all male
users of VA mental health services between 1994 and 1997, a total of 15.7 percent
39.6 percent of those age 18 to 39 years and 9.1 percent of those age 40 years
and older-were incarcerated at some time during that period. Dual diagnosis
patients had the highest rate of incarceration (25 percent), followed by patients
with substance abuse problems only (21 percent) and those with mental health
problems only (11 percent). The rate of incarceration among male patients
hospitalized in VA facilities was lower than among men in general hospitals or
state hospitals (11.6 percent, 23 percent, and 21.7 percent, respectively), but
was not significantly different. No significant increase occurred in the annual
rate of incarceration among VA patients from 1994 to 1997 (3.7 percent to 4
percent), despite extensive VA bed closures during these years. CONCLUSIONS:
Substantial proportions of mental health system users were incarcerated during
the study period, especially younger men and those with both substance use and
mental health disorders. Rates of incarceration were similar across health care
systems. The closure of a substantial number of VA mental health inpatient beds
did not seem to affect the rate of incarceration among VA service users.
PMID- 11013329
TI - The relationship between command hallucinations and violence.
AB - OBJECTIVE: The purpose of this study was to describe the relationship between
command hallucinations and violent behavior. METHODS: One hundred and three
psychiatric inpatients completed measures of command hallucinations, other
psychotic symptoms, violent behavior, and social desirability response biases.
RESULTS: Thirty percent of the patients reported having had command
hallucinations to harm others during the last year, and 22 percent of the
patients reported they complied with such commands. Logistic regression analyses
suggested that patients who experienced command hallucinations to harm others
were more than twice as likely to be violent, even when the analysis controlled
for demographic variables, history of substance abuse, and social desirability
response biases. CONCLUSIONS: The results support the clinical utility of asking
about command hallucinations when assessing the risk of violence in patients with
major mental disorders.
PMID- 11013330
TI - Help seeking by persons of Mexican origin with functional impairments.
AB - OBJECTIVE: Mexican Americans have low rates of service utilization for mental
health problems. This study examined the use of health services by persons who
have symptoms of mental distress that they say impair their ability to function.
METHODS: A stratified field survey was conducted in central California to select
a probabilistic sample of persons of Mexican origin. A multinomial logistic
regression was used for the analysis. RESULTS: Among respondents who reported
functional impairments attributable to their symptoms, 58 percent met diagnostic
criteria for a mental disorder. Of that group, 69 percent did not use any health
services. Respondents who sought medical services for mental health symptoms were
more likely to be women and to meet diagnostic criteria for a mental disorder.
Respondents who sought mental health services for their symptoms were more likely
to be female, to be unmarried, and to have had 12 or more years of education.
Health insurance status was not associated with type of service used.
CONCLUSIONS: Even among Mexican Americans who met diagnostic criteria for a
mental illness, most did not use services of any sort, and many of those who
sought treatment for their symptoms turned to medical and informal services.
PMID- 11013331
TI - Principal and additional DSM-IV disorders for which outpatients seek treatment.
AB - OBJECTIVE: Epidemiological studies indicate that most patients in the community
do not get treatment for psychiatric disorders. It is unknown whether persons who
present for outpatient psychiatric services seek treatment for all the disorders
they have or only for the principal disorder for which they are seeking
treatment. The goal of this study was to determine which axis I psychiatric
disorders motivate patients to seek treatment. METHODS: Four hundred outpatients
at a hospital-affiliated, community-based, psychiatric clinical practice were
interviewed with the Structured Clinical Interview for DSM-IV (SCID). For
patients with more than one disorder, the diagnoses were assigned as principal or
additional according to the DSM-IV convention of whether it was the patient's
stated primary reason for presenting for treatment or was an additional disorder.
For all current disorders, patients were asked whether the symptoms of each
diagnosed disorder were a reason, or one of the reasons, for seeking treatment.
RESULTS: Nearly all patients with major depression wanted treatment for this
disorder, and more than 85 percent of patients with panic disorder, posttraumatic
stress disorder, and generalized anxiety disorder indicated that the symptoms of
these disorders were a reason for seeking treatment. Half to two-thirds of
patients with social phobia, obsessive-compulsive disorder, intermittent
explosive disorder, body dysmorphic disorder, and substance use disorders
reported that the symptoms of these disorders were a reason for seeking
treatment. Only 30 percent of those with specific phobia indicated that their
phobic fears were a reason for seeking treatment. CONCLUSIONS: Patients often
seek treatment for symptoms of disorders that are diagnosed as comorbid, rather
than principal, conditions. It is important for clinicians to conduct thorough
diagnostic interviews in order to diagnose disorders that are not related to the
patient's chief complaint, as patients often desire treatment for these
additional diagnoses.
PMID- 11013332
TI - Satisfaction of forensic psychiatric patients with remote telepsychiatric
evaluation.
AB - The level of satisfaction with telepsychiatry evaluations was determined in a
sample of 43 forensic psychiatric patient inmates in a large urban jail. A
forensic psychiatrist interviewed 20 patients in person, the other 23 remotely
via interactive video. Demographic characteristics, physical health status, and
psychiatric symptom severity on the Global Severity Index of the Brief Symptom
Inventory were comparable in the two groups. Patient satisfaction with the
evaluations was moderately high for patients in both groups, with no significant
differences between them.
PMID- 11013333
TI - Establishing a function-based mental health service line in a VA medical center.
AB - From 1994 through 1996, a general Veterans Affairs (VA) medical center
reorganized its mental health services from a traditional discipline-based
structure to a unitary service line organized around patient care functions. A
comparison of data from 1993 and 1997 indicated increased efficiency, substantial
transfer of patients from inpatient to outpatient care, and growth in academic
programs not explainable solely by temporal, regional, or national trends or by
trends within the VA medical center. Although the results should be interpreted
conservatively because of the observational nature of the study, the
reorganization appeared to facilitate the positive changes that occurred over the
study period.
PMID- 11013334
TI - Coping resources of African-American and white patients hospitalized for bipolar
disorder.
AB - Forty-two African-American and 80 white patients hospitalized for bipolar
disorder completed the Coping Resources Inventory. Total resource scores of the
African Americans were significantly higher than scores of the whites, although
differences in background variables between the two groups were not evident. The
African-American group also scored significantly higher than the whites on the
three scales indicating internal resources-cognitive, emotional, and spiritual
philosophical. No statistically significant differences were found for the two
groups on the social and physical scales. Cultural orientations influencing
personal life philosophies may explain the differences between the African
American and white patients on perceptions of their coping resources.
PMID- 11013335
TI - Identifying and using reinforcers to enhance the treatment of persons with
serious mental illness.
AB - Successful engagement of clients with serious and persistent mental illnesses in
the planning and implementation of treatment requires the identification of
individualized reinforcers through motivational analyses. Reinforcer surveys are
interviews or questionnaires that list numerous objects, persons, activities, and
settings, and then assess the client's perception of the value of each item. Such
surveys help identify the type of reward that might be useful for motivating the
client. If properly assessed and delivered, reinforcers can increase clients'
skill acquisition, attainment of goals, and feelings of self-efficacy.
PMID- 11013336
TI - Improving police response to mentally ill people.
PMID- 11013337
TI - Linking discharged patients with peers in the community.
PMID- 11013338
TI - "I vote. I count.".
PMID- 11013339
TI - Tarasoff warnings.
PMID- 11013340
TI - Seclusion and restraints.
PMID- 11013342
TI - 1alpha-Hydroxylase and the action of vitamin D.
AB - The active form of vitamin D, 1,25-dihydroxvitamin D(3) (1, 25(OH)(2)D(3)), is a
pleiotropic hormone whose actions include the regulation of calcium homeostasis,
control of bone cell differentiation and modification of immune responses.
Synthesis of 1, 25(OH)(2)D(3) from the major circulating metabolite, 25
hydroxyvitamin D(3) (25(OH)D(3)), is catalysed by a mitochondrial cytochrome P450
enzyme, 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase). Although 1alpha
OHase is expressed predominantly in the kidney, extra-renal production of
1,25(OH)(2)D(3) has also been demonstrated in tissues such as lymph nodes and
skin. The tight regulation of 1alpha-OHase which occurs in both renal and
peripheral tissues has made studies of the expression and regulation of this
enzyme remarkably difficult. However, the recent cloning of mouse, rat and human
cDNAs for 1alpha-OHase (CYP1alpha/Cyp1alpha) has enabled a more thorough
characterization of this enzyme. In particular, analysis of the CYP1alpha gene
has identified mutations causing the inherited disorder vitamin D-dependent
rickets type 1, also known as pseudo-vitamin D deficiency rickets. Studies from
our own group have focused on the distribution of 1alpha-OHase in both renal and
extra-renal tissues. Data indicate that the enzyme is expressed throughout the
nephron, suggesting discrete endocrine and paracrine/autocrine functions. Further
immunohistochemical analyses have shown that the enzyme is widely distributed in
extra-renal tissues, and this appears to be due to the same gene product as the
kidney. Collectively, these observations have raised important new questions
concerning the role of 1alpha-OHase in vitamin D signalling at a local level. The
relationship between expression of protein for 1alpha-OHase and enzyme activity
has yet to be fully characterized and may be dependent on membrane proteins such
as megalin. Similarly, elucidation of the mechanisms involved in differential
regulation of renal and extra-renal 1,25(OH)(2)D(3) production will be essential
to our understanding of the tissue-specific functions of 1alpha-OHase. These and
other issues are discussed in the current review.
PMID- 11013343
TI - Role of aromatase in sex steroid action.
PMID- 11013344
TI - Molecular evolution of the growth hormone-releasing hormone/pituitary adenylate
cyclase-activating polypeptide gene family. Functional implication in the
regulation of growth hormone secretion.
AB - Growth hormone-releasing hormone (GHRH) and pituitary adenylate cyclase
activating polypeptide (PACAP) belong to the same superfamily of regulatory
neuropeptides and have both been characterized on the basis of their
hypophysiotropic activities. This review describes the molecular evolution of the
GHRH/PACAP gene family from urochordates to mammals and presents the hypothesis
that the respective roles of GHRH and PACAP in the control of GH secretion are
totally inverted in phylogenetically distant groups of vertebrates. In mammals,
GHRH and PACAP originate from distinct precursors whereas, in all submammalian
taxa investigated so far, including birds, amphibians and fish, a single
precursor encompasses a GHRH-like peptide and PACAP. In mammals, GHRH-containing
neurons are confined to the infundibular and dorsomedial nuclei of the
hypothalamus while PACAP-producing neurons are widely distributed in hypothalamic
and extrahypothalamic areas. In fish, both GHRH- and PACAP-immunoreactive neurons
are restricted to the diencephalon and directly innervate the adenohypophysis. In
mammals and birds, GHRH plays a predominant role in the control of GH secretion.
In amphibians, both GHRH and PACAP are potent stimulators of GH release. In fish,
PACAP strongly activates GH release whereas GHRH has little or no effect on GH
secretion. The GHRH/PACAP family of peptides thus provides a unique model in
which to investigate the structural and functional facets of evolution.
PMID- 11013345
TI - Absolute quantification of mRNA using real-time reverse transcription polymerase
chain reaction assays.
AB - The reverse transcription polymerase chain reaction (RT-PCR) is the most
sensitive method for the detection of low-abundance mRNA, often obtained from
limited tissue samples. However, it is a complex technique, there are substantial
problems associated with its true sensitivity, reproducibility and specificity
and, as a quantitative method, it suffers from the problems inherent in PCR. The
recent introduction of fluorescence-based kinetic RT-PCR procedures significantly
simplifies the process of producing reproducible quantification of mRNAs and
promises to overcome these limitations. Nevertheless, their successful
application depends on a clear understanding of the practical problems, and
careful experimental design, application and validation remain essential for
accurate quantitative measurements of transcription. This review discusses the
technical aspects involved, contrasts conventional and kinetic RT-PCR methods for
quantitating gene expression and compares the different kinetic RT-PCR systems.
It illustrates the usefulness of these assays by demonstrating the significantly
different levels of transcription between individuals of the housekeeping gene
family, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH).
PMID- 11013346
TI - Identification of a novel calcitonin-response element in the promoter of the
human p21WAF1/CIP1 gene.
AB - The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is induced in many cell types
in response to a variety of extracellular signals and causes cell cycle arrest in
both the G1 and G2/M phases of the cell cycle. We reported previously that
calcitonin (CT) receptor (CTR)-mediated growth inhibition of HEK-293 cells stably
transfected with the human CTR is accompanied by a rapid and sustained induction
of p21 and cell cycle arrest in G2. In the present study we have shown that CT
stimulates transcription from a p21 promoter-luciferase construct. Using deletion
and mutation analysis of the p21 promoter we have demonstrated that
transcriptional activation of p21 by CT is p53-independent and is mediated
through specific activation of Sp1-binding sites in a region of the promoter
between -82 and -69, relative to the transcription start site. CTR-mediated
transcriptional activation of p21 was specific for the insert-negative isoform of
the human CTR. Butyrate, which was shown previously to activate the same Sp1
site, synergised with CT to increase further p21 promoter activity. These results
provide the first demonstration that CTR can induce gene transcription through
the constitutively expressed transcription factor Sp1, and define a mechanism of
cell growth suppression that may have implications for other members of the seven
transmembrane domain G protein-coupled receptor superfamily.
PMID- 11013347
TI - Oestradiol decreases rat apolipoprotein AI transcription via promoter site B.
AB - Oestrogens protect against ischaemic heart disease in the post-menopausal female
by increasing serum concentrations of apolipoprotein (apo) AI and the abundance
of high-density lipoprotein particles. In men and experimental male animals, the
administration of oestrogen has variable effects on apo AI expression. As the
major mode of oestrogen action on target genes involves regulating promoter
activity and hence transcription, oestrogen is expected to alter transcription of
the apo AI gene. To test this hypothesis, the effect of 17beta-oestradiol (E(2)),
on rat apo AI promoter activity in male hepatoma HuH-7 cells, was tested by co
transfecting a reporter template, pAI.474.CAT containing-474 to-7 of the rat apo
AI promoter and an oestrogen receptor (ER) expression vector, pCMV-ER.
Transfected cells exposed to E(2) showed a dose-dependent decrease in
chloramphenicol acetyltransferase (CAT)-activity, with a maximum 91+/-1.5%
reduction at 1 microM E(2). Deletional analysis of the promoter localized the
inhibitory effect of ER and E(2) to site B (-170 to-144) with an adjacent 5'
contiguous motif, site S (-186 to-171) acting as an amplifier. HuH-7 cell nuclear
extracts showed binding activities with both sites S and B, but recombinant human
ER did not. Furthermore, nuclear extracts from E(2)-treated HuH-7 cells showed
weaker binding activity to site B, but not to site S. In summary, the inhibitory
effect of ER and E(2) on rat apo AI gene activity is mediated by a promoter
element, site B. This inhibitory effect arises from a mechanism that does not
involve direct ER binding to the B-element. The conclusion that E(2) inhibits apo
AI transcription was confirmed in vivo. Treatment of male adult Sprague-Dawley
rats with up to 200 microg E(2) for 7 days decreased apo AI protein and hepatic
mRNA by 72+/-21% and 68+/-1.4% respectively. Results of 'run-on' transcription of
the apo AI gene in isolated hepatic nuclei showed a 55% decrease in hormone
treated male rats. These findings suggest that E(2) exerts primarily an
inhibitory effect within male hepatic nuclei.
PMID- 11013348
TI - Characterization of a human 20alpha-hydroxysteroid dehydrogenase.
AB - It has been suggested that 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) is
a T-cell differentiation marker in mice. In the human, this enzyme has generally
been associated with types 1 and 2 17beta-HSDs, which belong to the short-chain
alcohol dehydrogenase family, whereas the rat, rabbit, pig and bovine 20alpha
HSDs are members of the aldoketo reductase superfamily, which also includes the
3alpha-HSD family. In this study, we report the cloning, from a human skin cDNA
library, of a cDNA that shows, after transfection into human embryonic kidney
(HEK-293) cells, high 20alpha-HSD activity but negligible 3alpha- and 17beta
hydroxysteroid dehydrogenase activities. A comparison of the amino acid sequence
of the human 20alpha-HSD with those of other related 20alpha- and 3alpha-HSDs
indicates that the human 20alpha-HSD shares 79.9, 68.7 and 52.3% identity with
rabbit, rat and bovine 20alpha-HSDs, whereas it shows 97, 84 and 65% identity
with human type 3, type 1 and rat 3alpha-HSDs. In contrast, the enzyme shares
only 15.2 and 15.0% identity with type 1 and type 2 human 17beta-HSDs. DNA
analysis predicts a protein of 323 amino acids, with a calculated molecular
weight of 36 767 Da. In intact transfected cells, the human 20alpha-HSD
preferentially catalyzes the reduction of progesterone to 20alpha
hydroxyprogesterone with a K(m) value of 0.6 microM, the reverse reaction
(oxidation) being negligible. In a cell cytosolic preparation, the enzyme could
use both NADPH and NADH as cofactors, but NADPH, which gave 4-fold lower K(m)
values, was preferred. We detected the expression of 20alpha-HSD mRNA in liver,
prostate, testis, adrenal, brain, uterus and mammary-gland tissues and in human
keratinocyte (HaCaT) cells. The present study clearly indicates that the genuine
human 20alpha-HSD belongs to the aldoketo reductase family, like the 20alpha-HSDs
from other species.
PMID- 11013349
TI - Functional characteristics of a novel murine estrogen receptor-beta isoform,
estrogen receptor-beta 2.
AB - We have isolated a highly expressed splice variant mRNA of murine estrogen
receptor-beta (ERbeta), mERbeta2, containing an in-frame 54 nucleotide insertion
between exons 5 and 6 of wild-type mERbeta1. The predicted ERbeta2 protein
contains 18 amino acids inserted in the ligand binding domain of mERbeta1.
Recombinant protein generated by in vitro transcription/translation showed that
mERbeta2 had markedly reduced ligand binding (K(D)=17.7+/-4.7 nM, mean+/-s.e.m.,
n=3) compared with mERbeta1-bound (3)H-estradiol (K(D)=0.56+/- 0.19 nM, mean+/
s.e.m., n=3). Both receptors bound similarly to palindromic estrogen responsive
elements (EREs) in vitro and in vivo, and similarly bent DNA. Transcriptional
activity was assessed using transient transfection analysis into a homologous
murine cell line, NIH 3T3 cells. mERbeta1 transactivated ERE-tk-CAT reporter
genes similarly to mERalpha, whereas mERbeta2 had little activity except at high
ligand concentrations. However, under conditions in which mERbeta2 is unlikely to
be ligand saturated, co-transfected mERbeta2 inhibited activity of mERalpha and
possibly mERbeta1 on ERE-tk-CAT genes. Using a 'novel raloxifene responsive' gene
reporter system (TGF-beta3-CAT), we found the ability of estradiol and LY117018
to activate both mERalpha and mERbeta1 on this promoter was identical, and
mERbeta2 activity in the presence of either estradiol or LY117018 was only
slightly less than that observed with either mERbeta1 or mERalpha. Both mERbeta1
and mERbeta2 when liganded with LY117018 inhibited transcription at a classical
ERE-regulated promoter under these transfection conditions, which was in marked
contrast to their stimulatory effect at the transforming growth factor-beta3
promoter. These data suggest that responsiveness of gene expression to a
relatively highly expressed variant murine ERbeta isoform, mERbeta2, is both
ligand and promoter specific. Determination of the relative level of expression
of mERbeta1 mRNA and mERbeta2 mRNA in mouse tissues indicated predominance of
mERbeta2 mRNA in some but not all tissues. These data suggest that the mERbeta2
may have some tissue-specific and promoter-specific modulatory effects.
PMID- 11013350
TI - Quantification of rainbow trout (Oncorhynchus mykiss) estrogen receptor-alpha
messenger RNA and its expression in the ovary during the reproductive cycle.
AB - This study developed a quantitative reverse transcription-polymerase chain
reaction (RT-PCR) method to measure estrogen receptor-alpha (ERalpha) mRNA in the
rainbow trout (Oncorhynchus mykiss). Using RT-PCR, and primers based on the known
ERalpha DNA sequence in this species, cDNA sequences representing most of the
protein coding region were obtained from ovary poly A(+) RNA. Using these DNA
sequences as probes in Northern blot hybridizations confirmed that a single
transcript of 4.2 kilobases in poly A(+) RNA could be detected in liver and ovary
RNA. For the quantitative RT-PCR assay an internal standard RNA molecule was
produced to control for inherent inter-tube differences in amplification
efficiency and permit accurate quantification of ERalpha mRNAs. The quantitative
RT-PCR assay proved to be highly specific for ERalpha mRNA with a detection limit
of 6.9 fg, which corresponds to 273 fg ERalpha mRNA/microg total RNA. The
quantitative RT-PCR assay was used to measure the levels of ERalpha mRNA in
ovaries of rainbow trout at different stages of reproductive development. Ovarian
ERalpha mRNA expression was found during two distinct periods of reproductive
development, in pre-vitellogenic ovaries of fish with ovarian follicle diameters
(OFDs) =100 microm and in mid-vitellogenic ovaries with OFDs >1000 microm.
ERalpha mRNA could not be detected in the ovaries of fish with OFDs >100 microm
but =1000 microm. The highest levels of ERalpha mRNA were found in late
vitellogenic ovaries of fish with OFDs >2000 microm.
PMID- 11013351
TI - Induction of erythroid proliferation and differentiation by a trophoblast
specific cytokine involves activation of the JAK/STAT pathway.
AB - Pregnancy is characterized by increased erythropoiesis within maternal and fetal
compartments. The placenta has been shown to produce factors that stimulate
erythropoiesis but convincing evidence for placental production of erythropoietin
(EPO) is still lacking. Prolactin-like protein E (PLP-E) was recently found to
stimulate expression of the adult beta major globin gene in mouse erythroleukemia
cells. Here we demonstrate that PLP-E transiently expressed in COS-7 cells
stimulates proliferation and erythroid differentiation of murine and human
erythroid progenitor cell lines. Electrophoretic mobility shift assays were used
to show the activation of STAT5 by PLP-E in the human erythroid cell line TF1.
Furthermore, we compared the effects of PLP-E on murine myeloid FDCP1 cells which
do not express EPO receptors (EPORs) with effects on cells genetically engineered
to express functional EPORs. We provide evidence that PLP-E-dependent
proliferation and STAT5 activation is independent of the expression of the EPOR.
Taken together, these data suggest that PLP-E acts on specific receptors of
erythroid-committed murine and human cells by the activation of intracellular
signaling pathways promoting cell growth and differentiation.
PMID- 11013352
TI - CYFRA 21-1 determination in patients with esophageal squamous cell carcinoma:
clinical utility for detection of recurrences.
AB - BACKGROUND: While there are reports that CYFRA 21-1 is a useful tumor marker, to
our knowledge the clinical utility of this marker to detect recurrences for
squamous cell carcinoma of the esophagus has not been addressed. METHODS: By
immunoradiometric assay, human serum levels of CYFRA 21-1, SCC antigen and CEA
were measured in esophageal squamous cell carcinoma patients prior to their
initial treatment. Monthly follow-ups of these tumor markers was done after
surgery. RESULTS: The diagnostic sensitivity of CYFRA 21-1 was 43.9% (18 of 41),
a value superior to that for SCC antigen (26.8%) and CEA (17.0%) (P < 0.05). The
positive rates of CYFRA 21-1 increased with progression of the disease, 22.2% of
pTNM Stage 0-IIA and 77.8% of pTNM Stage IIB/III (P = 0.013), whereas SCC antigen
and CEA rates were not related to pTNM stage. Among 13 patients with clinical
evidence of a recurrence, 76.9% (10 of 13) exhibited an increase in CYFRA 21-1,
and this increase was evident before clinical detection of the recurrence in 9 of
these 13 patients (69.2%). Consequently, postoperative elevations of serum CYFRA
21-1 levels were indicative of a tumor recurrence 1-13 months before acquisition
of clinical and radiological data. CONCLUSIONS: The assay of CYFRA 21-1 is useful
not only for diagnosis but also for close monitoring of patients with esophageal
squamous cell carcinoma.
PMID- 11013353
TI - Pathology and prognosis of gastric carcinoma: well versus poorly differentiated
type.
AB - BACKGROUND: The most important parameters predicting outcome of patients with
gastric carcinoma are the depth of wall invasion and the status of lymph node
metastasis, but the prognostic significance of histologic type is unclear. The
aim of this study was to clarify the prognostic value of two major histologic
types of gastric carcinoma, that is well and poorly differentiated types.
METHODS: Histopathologic findings and outcomes of 504 patients with gastric
carcinoma were evaluated by well and poorly differentiated types. Well
differentiated gastric carcinoma (WGC) included papillary and tubular
adenocarcinomas, poorly differentiated medullary carcinoma, and well
differentiated mucinous carcinoma; whereas poorly differentiated gastric
carcinoma (PGC) included poorly differentiated scirrhous carcinoma, signet ring
cell carcinoma, and poorly differentiated mucinous carcinoma. RESULTS: Patients
with WGC were characterized by old age, male predominance, tumor location in the
lower third of the stomach, small tumor size, and liver metastasis; whereas
patients with PGC were distinguished by their tumor location in the middle third
of the stomach, serosal invasion, lymph node metastasis, advanced stage, and
peritoneal dissemination. The overall 5-year survival rate for patients with WGC
was higher than that for patients with PGC (76% vs. 67%; P = 0.058), especially
for patients with >/= 10 cm tumors (42% vs. 14%; P = 0.017). The 5-year survival
rate for patients with serosa positive but node negative tumors was higher in WGC
patients than in PGC patients (83% vs. 59%; P = 0.086); whereas the 5-year
survival rate for patients with serosa negative but node positive tumors was
lower in WGC patients than in PGC patients (63% vs. 88%; P = 0.008). Multivariate
analysis indicated that among pathologic variables of the tumor, histologic type
(WGC vs. PGC) was one of the independent prognostic factors. CONCLUSIONS:
Histologic type is important for estimating the tumor progression and outcomes of
patients with gastric carcinoma. In addition to the depth of wall invasion and
status of lymph node metastasis, histologic type, including well or poorly
differentiated type, should be evaluated in the management of gastric cancer.
PMID- 11013354
TI - Outcome of prophylactic radical lymphadenectomy with gastrectomy in patients with
early gastric carcinoma without lymph node metastasis.
AB - BACKGROUND: Prophylactic extended lymphadenectomy with gastrectomy may prolong
survival in patients with early gastric carcinoma without lymph node metastasis.
However, the therapeutic value of extensive lymphadenectomy in patients with
early gastric carcinoma remains controversial. METHODS: The authors
retrospectively analyzed 423 patients with early gastric carcinoma without lymph
node metastasis who underwent gastrectomy and did not die of other diseases to
evaluate the effect of prophylactic extended lymphadenectomy on postoperative
survival. The postoperative survival rate of patients who underwent prophylactic
extended lymphadenectomy was compared with that of patients who underwent
prophylactic limited lymphadenectomy. RESULTS: Although extended lymphadenectomy
did not appear to improve the postoperative survival rate of patients with
mucosal tumors, it did improve the postoperative survival rate of patients with
submucosal tumors. Whether prophylactic extended lymphadenectomy was performed
significantly affected outcome in patients with early gastric carcinoma who had
submucosal tumors without regional lymph node metastasis. CONCLUSIONS: Extensive
lymphadenectomy with gastrectomy should be performed to prolong the survival of
the patients with submucosal tumors.
PMID- 11013355
TI - Detection of Helicobacter species in the liver of patients with and without
primary liver carcinoma.
AB - BACKGROUND: Several studies have shown the presence of Helicobacter species in
the human biliary tract and in the intestinal tract of animals. In this study,
the presence of Helicobacter species in liver samples from patients with primary
hepatic carcinomas was evaluated. METHODS: Sixteen liver specimens were studied
(8 from patients with primary liver carcinoma and 8 from patients without primary
liver carcinoma). Histology with standard stains, culture, and polymerase chain
reaction (PCR) amplification using two sets of primers located in the 16S
ribosomal DNA (rDNA) were used to detect the presence of bacteria. Amplified
products were sequenced to determine the genus and species of the bacteria. A
search for other genes that were specific for Helicobacter pylori also was
carried out by PCR. RESULTS: PCR performed with the 16S rDNA primers revealed the
presence of bacteria from the genus Helicobacter in all of the liver specimens
from patients with primary liver carcinoma (eight of eight patients) and in one
specimen from a patient without primary liver carcinoma (one of eight patients).
When the nucleotide sequence of > 80% of the 16S rDNA was determined, the closest
similarity was with the 16S rDNA from H. pylori in eight patients. In 1 patient
sample from which only 398 nucleotides were sequenced, the closest match was
Helicobacter felis. CONCLUSIONS: The results presented in this study indicate
that Helicobacter species can be present in the liver of patients with primary
hepatic carcinoma, but their eventual role in the carcinogenesis process,
although it is plausible, remains to be proven. Based on sequence similarity, it
seems that Helicobacter species that are related closely to H. pylori but are
distinct from it have been found.
PMID- 11013356
TI - Glutathione depletion causes cell growth inhibition and enhanced apoptosis in
pancreatic cancer cells.
AB - BACKGROUND: Recent studies have demonstrated that various tumors express enhanced
levels of the radical scavenger glutathione (GSH). Moreover, there are grounds
for claiming that GSH plays a crucial role in cell proliferation and tumor
resistance. In the current study, we investigated the relation between cell
growth and GSH levels in the pancreatic adenocarcinoma cell line, AsPC-1, and the
significance of GSH in tumor resistance to chemotherapy. METHODS: Cell growth in
AsPC-1 was initiated through transforming growth factor-alpha (TGF-alpha) or
fetal calf serum (FCS). Then, cell cycle, cell proliferation, and cellular GSH
content were analyzed at different times in the presence or absence of buthionine
sulfoximine (BSO). The impact of GSH on chemotherapy-induced apoptosis was
studied using 5-fluorouracil or melphalan in the presence or absence of BSO.
Finally, we compared the GSH content of 15 pancreatic tumor specimens with 10
normal pancreatic tissue specimens. RESULTS: Analysis of GSH in pancreatic
tissues demonstrated increased GSH levels in cancerous compared with normal
tissue (17.5 +/- 2.3 vs. 8. 8 +/- 1.4 nmol/mg protein; P < 0.004). Incubation of
AsPC-1 with TGF-alpha or FCS resulted in cell proliferation and cell cycle
activity, whereas GSH content was not altered. Incubation of GSH-depleted cells
with TGF-alpha did not stimulate cell growth. In addition, GSH-depletion resulted
in an increased rate of apoptosis after melphalan (6.3 +/- 0.3 % vs. 11.2 +/- 0.3
%; P < 0.001), but not after 5-fluorouracil treatment. CONCLUSIONS: Taken
together, our results show enhanced GSH levels in pancreatic carcinoma and an
essential role of GSH in cell proliferation and in resistance of AsPC-1 cells.
Therefore, GSH-depletion may improve the efficacy of adjuvant therapy in
pancreatic carcinoma.
PMID- 11013357
TI - Increased secretory leukoprotease inhibitor in patients with nonsmall cell lung
carcinoma.
AB - BACKGROUND: It is well known that acute pulmonary inflammation, such as that
observed in pneumonia, elevates secretory leukoprotease inhibitor (SLPI) levels
in serum. A previous report indicated that serum SLPI levels in lung carcinoma
patients with concurrent pneumonia were significantly higher than in those in
patients whose disease was unaccompanied by pneumonia or in healthy subjects. The
authors hypothesized that serum SLPI may increase in patients with lung
carcinoma, even carcinoma occurring without pneumonia, and that cells in lung
carcinoma might produce SLPI. METHODS: Serum SLPI levels in 58 patients with
primary lung carcinoma unaccompanied by pneumonia and in 42 healthy subjects were
measured by an enzyme immunoassay. Twenty-four specimens from 24 of the patients
with primary lung carcinoma also were examined immunohistochemically using the
rabbit antihuman SLPI antibody. RESULTS: The results of the current study
confirmed that the serum levels of SLPI in patients with primary lung carcinoma
were higher than those in healthy subjects, and further found there was no
significant correlation between serum SLPI levels and C-reactive protein in lung
carcinoma patients without pneumonia. When classifying primary lung carcinoma by
its histology, SLPI levels in patients with adenocarcinoma and squamous cell
carcinoma were significantly higher than in those in patients with small cell
lung carcinoma (SCLC). In patients with nonsmall cell lung carcinoma (NSCLC), the
SLPI levels in the advanced group (International Union Against Cancer Stages III
and IV disease; n = 35) were significantly elevated compared with the nonadvanced
group (Stages I and II disease; n = 12), and such elevated SLPI levels were
reduced in some cases by an efficient response to surgical therapy or
chemotherapy. Immunohistochemical studies showed that all the NSCLC tissues were
stained with anti-human SLPI antibody, whereas staining was not noted in any of
the SCLC tissues. CONCLUSIONS: The authors believe that the findings of the
current study demonstrate that cells of NSCLC produce SLPI. Furthermore, they
suggest that serum SLPI levels in serum may be a helpful marker in patients with
NSCLC unaccompanied by pneumonia, and that SLPI also could be used as an
immunohistochemical marker to distinguish between NSCLC and SCLC.
PMID- 11013358
TI - Ki-67 immunostaining and other prognostic factors including tobacco smoking in
patients with resected nonsmall cell lung carcinoma.
AB - BACKGROUND: To estimate the effectiveness of expression of the tumor
proliferative marker Ki-67 antigen (Ki-67) as a postoperative prognostic marker,
the authors analyzed Ki-67 expression and its correlation with postoperative
survival and other clinicopathologic factors, including preoperative smoking
habits, in patients with resected nonsmall cell lung carcinoma (NSCLC). METHODS:
A total of 156 patients with resected NSCLC at the study institution were
investigated. Postoperative survival rates were estimated based on demographic
and clinicopathologic factors, including Ki-67 expression and preoperative
tobacco smoking habits. RESULTS: The overall postoperative 5-year survival rate
in patients with high Ki-67 labeling indices (>/= 20%) was 39.6% compared with
67.7% in patients with low Ki-67 labeling indices. This finding was significant
for all resected cases and for each pathologic disease stage (P < 0.05). The
postoperative 5-year survival rate in patients with a history of heavy smoking
(>/= 30 pack-years) was 47.6% compared with 62.5% for other patients (P = 0.027).
This result was especially significant in patients with International Union
Against Cancer Stage I disease and in patients with nonsquamous cell carcinoma (P
< 0.03). The authors also observed a positive correlation between the Ki-67
labeling index and preoperative smoking habits (P = 0.0002). Multivariate
analysis demonstrated that lymph node involvement, tumor differentiation, and Ki
67 labeling index were significant prognostic factors in NSCLC (P < 0.01).
CONCLUSIONS: Tumor Ki-67 expression is a strong prognostic factor in NSCLC,
especially adenocarcinoma. It may be hypothesized that tobacco mutagenicity may
play a role in the growth and extension of NSCLC, which is one of the major
impediments to postoperative survival in patients with a history of heavy
smoking.
PMID- 11013359
TI - Expression of connective tissue growth factor in cartilaginous tumors.
AB - BACKGROUND: Connective tissue growth factor (CTGF) predominantly is expressed in
hypertrophic chondrocytes and its specific receptors are demonstrated on
chondrocytic cells. Therefore, CTGF may be involved in the proliferation and/or
differentiation of cartilage cells. In the current study, CTGF expression was
examined both in chondrosarcoma and enchondroma to clarify the relation between
the expression of CTGF and the grade of malignancy. METHODS: The expression of
CTGF and proliferating cell nuclear antigen (PCNA) were analyzed
immunohistochemically in 34 cartilaginous tumor specimens. Eighteen tumors were
determined to be chondrosarcoma including 8 Grade 1 tumors, 6 Grade 2 tumors, and
4 Grade 3 tumors. The percentage of CTGF positive and PCNA positive cells was
quantified using at least 500 cells. RESULTS: CTGF was expressed in 70.1% of
enchondroma cells, 84.0% of Grade 1 chondrosarcoma cells, 53.7% of Grade 2 tumor
cells, and 26.8% of Grade 3 tumor cells (rho = -0.501; P = 0.0053). In
chondrosarcoma cases, CTGF expression was correlated closely with tumor grade
(rho = -0.920; P = 0.0001). There was a strong correlation between PCNA
expression and tumor grade (rho = 0.907; P < 0.0001) and a strong negative
correlation between CTGF and PCNA expression (rho = -0.493; P = 0.0061). In
chondrosarcoma cases, patients with high expression of CTGF (>/= 30%) showed
higher overall survival compared with those with low expression (< 30%) (P =
0.004). CONCLUSIONS: The current study revealed a correlation between the
histologic grade of chondrosarcoma and prognosis, and the concomitant association
between CTGF immunostaining and tumor grade and prognosis. Therefore,
immunohistochemical staining with CTGF is a useful procedure for assessing the
tumor grade and clinical course in patients with chondrosarcoma.
PMID- 11013360
TI - Circulating CD44 and intercellular adhesion molecule-1 levels in low grade non
hodgkin lymphoma and B-cell chronic lymphocytic leukemia patients during
interferon-alpha-2a treatment.
AB - BACKGROUND: Despite published reports regarding the association of elevated
circulating CD44 and CD54 levels with unfavorable outcome in non-Hodgkin lymphoma
(NHL) and chronic lymphocytic leukemia (CLL), little is known about therapy
related changes in either adhesion molecule. In an attempt to evaluate the effect
of interferon-alpha (IFNalpha), the authors measured serum CD44 (sCD44) and sCD54
in 22 low grade NHL and 14 CLL patients. METHODS: Twenty-six patients fulfilling
the criteria for therapy received daily doses of 3 x10(6) IU IFNalpha-2a. Ten
patients not requiring therapy also were observed for the same period. Fasting
sera were collected at baseline and in 4 monthly intervals from all patients
including the IFNalpha-treated (Group 1) and the untreated group (Group 2).
RESULTS: Higher baseline sCD44 values were observed in Group 1 as compared with
the Group 2 patients (P = 0.057). Within Group 1, patients were further divided
between those who responded to IFNalpha, referred to as responders, and those who
did not respond to IFNalpha, known as nonresponders. Responders showed a gradual
decrease in sCD44 starting at the 4th month until the 12th month (P = 0.003, P =
0.002, and P = 0.01). Neither a difference in baseline nor an IFNalpha effect on
the sCD54 levels could be shown. Soluble CD44 levels between responders and
nonresponders were not different at the baseline but were significantly lower in
responders, starting at month 4 and continuing throughout the therapy period (P =
0.04, P = 0.017, and P = 0.043). This decrease did not accompany a leukocyte or
lactate dehydrogenase decrease and was not correlated with an early disappearance
of the clinical findings. Similarly, after treatment, the sCD44 values of Group 1
were lower than the Group 2 levels at months 4 and 8 (P = 0.007 and P = 0.05,
respectively). CONCLUSIONS: Soluble CD44, but not sCD54, can be used for
monitoring therapy in patients with low grade NHL and CLL who have received
IFNalpha, and for deciding whether further IFN therapy is necessary for those
patients who have not responded to IFNalpha over a previous 12-month period.
PMID- 11013361
TI - Avascular necrosis of the femoral head in chronic myeloid leukemia patients
treated with interferon-alpha: a synergistic correlation?
AB - BACKGROUND: The objectives of this study were to describe cases of avascular
necrosis of the femoral head (ANFH) observed in chronic myeloid leukemia (CML)
patients who were treated with interferon-alpha and to review the literature.
METHODS: The authors undertook a case review of the M. D. Anderson experience
with ANFH occurring in CML patients who were managed with interferon-alpha-based
therapy. MEDLINE (from 1966 to November 1999) and CancerLit (from 1983 to
November 1999) searches were conducted to identify cases of avascular necrosis
(AVN) associated with either CML or interferon-alpha. RESULTS: Three patients
with ANFH were identified from the authors' experience. No common features
related to the disease or therapy were seen among them, except for the presence
of thrombocytosis and loss of response. A literature review revealed seven cases
of ANFH associated with CML with or without interferon-alpha-based therapy. ANFH
was not reported in association with interferon-alpha use for indications other
than the treatment of patients with CML. CONCLUSIONS: ANFH may be the result of
an interaction between CML and interferon-alpha therapy. ANFH that occurs in
patients with CML who are treated with interferon-alpha should be recognized for
treatment implications. Thrombocytosis with consequent microvascular thrombi and
avascular necrosis manifesting in susceptible vascular or weight-bearing areas
(e.g., the femoral head) may be an associated finding along with loss of response
to interferon-alpha therapy.
PMID- 11013362
TI - Intermediate dose recombinant interferon-alpha as second-line treatment for
patients with recurrent cutaneous melanoma who were pretreated with low dose
interferon.
AB - BACKGROUND: Interferon (IFN) is widely considered the most effective agent in the
adjuvant therapy of patients with cutaneous melanoma (CM). However, little is
known about the effect of IFN on pretreated CM patients who experience disease
recurrence. The authors conducted a Phase II study to determine whether
intermediate doses of IFN could be beneficial for these patients. METHODS: A
series of 24 consecutive CM patients who had undergone surgery for local, in
transit, or lymph node disease recurrence during adjuvant therapy with low dose
IFN (IFNalpha-2b, 3 million units [MU] per day, three times per week) were
enrolled for second-line therapy with intermediate dose IFN (IFNalpha-2b, 10 MU
per day) for one year. RESULTS: IFN was discontinued in 7 patients (29.2%)
because of toxicity. Several patients complained of impairment in their daily
activities. Progression of disease was registered in 17 patients (70. 8%), with a
median disease free survival of 5.5 months (95% confidence interval, 3.4-14.2).
The median follow-up for the 7 patients who did not experience disease recurrence
was 15 months (range, 13-22 months). CONCLUSIONS: An increased dose of IFN as
second-line adjuvant treatment was poorly tolerated and produced negative
clinical outcomes in patients with CM. However, these patients probably were
unresponsive to IFN regardless of the dosage level. In fact, the first adjuvant
IFN treatment was ineffective in all patients. Thus, the key factor in the
treatment of CM seems to be patient responsiveness to IFN rather than the total
dosage achieved.
PMID- 11013363
TI - Long term results of a randomized study by the Swedish Melanoma Study Group on 2
cm versus 5-cm resection margins for patients with cutaneous melanoma with a
tumor thickness of 0.8-2.0 mm.
AB - BACKGROUND: Large, prospective, randomized trials with long term follow-up are
required to obtain an unbiased evaluation of the significance of resection
margins in patients with cutaneous melanoma. METHODS: The Swedish Melanoma Study
Group performed a prospective, randomized, multicenter study of patients with
primary melanoma located on trunk or extremities and with a tumor thickness > 0.8
mm and = 2 mm. Patients were allocated randomly to a 2-cm excision margin or a
5-cm excision margin. In total, 989 patients were recruited during the period
1982-1991. The median follow-up was 11 years (range, 7-17 years) for estimation
of survival and 8 years (range, 0-17 years) for evaluation of recurrent disease.
RESULTS: The crude rate of local recurrence, defined as a recurrence in the scar
or transplant, was < 1% (8 of 989 patients). Twenty percent of the patients (194
of 989 patients) experienced any disease recurrence, and 15% (146 of 989
patients) died of melanoma. There were no statistically significant differences
between the two treatment arms. In a multivariate Cox analysis with patients
allocated to wide excision as the reference group, the estimated relative hazards
for overall survival and recurrence free survival among those allocated to a 2-cm
resection margin were 0.96 (95% confidence interval, 0.75-1.24), and 1.02 (95%
confidence interval, 0.80-1.30), respectively. CONCLUSIONS: In this long term
follow-up study, local recurrences were found to be rare among patients with
tumors > 0.8 mm thick and = 2.0 mm thick. No difference in recurrence rate or
survival between the two treatment groups was found. Patients in this category
can be treated with a resection margin of 2 cm as safely as with a resection
margin of 5 cm.
PMID- 11013364
TI - Primary treatment of cystosarcoma phyllodes of the breast.
AB - BACKGROUND: Cystosarcoma phyllodes is a rare sarcoma of the breast. Although
surgical removal is the mainstay of treatment, the extent of surgery required
(excision vs. mastectomy) and the need for additional local therapy, such as
radiotherapy, are unclear. The current study evaluated the rate of local and
distant failure, as well as potential prognostic factors, to better define
appropriate treatment strategies. METHODS: One hundred one patients treated
primarily for cystosarcoma phyllodes of the breast were evaluated. These tumors
were classified histologically into benign (58%), indeterminate (12%), and
malignant (30%) based on well defined criteria. Stromal overgrowth (29%) was
considered separately. Surgery was comprised of local excision with breast
conservation (47%) or mastectomy (53%). Microscopic surgical margins were
negative in 99% of cases. Six patients received adjuvant radiotherapy. RESULTS:
Overall survival for the 101 patients was 88%, 79%, and 62% at 5, 10, and 15
years, respectively. For patients with nonmalignant (benign or indeterminate) and
malignant cystosarcoma phyllodes, the overall survival was 91% and 82%,
respectively, at 5 years, and 79% and 42%, respectively, at 10 years. Similar
rates were observed based on the presence or absence of stromal overgrowth. Local
recurrence occurred in 4 patients, with an actuarial 10-year rate of 8%. Eight
patients developed distant metastases, with an actuarial 10-year rate of 13%.
Multivariate analysis using Cox proportional hazards regression revealed stromal
overgrowth to be the only independent predictor of distant failure. CONCLUSIONS:
Local failure in this group of largely margin negative patients with cystosarcoma
phyllodes of the breast was low, showing that breast-conserving surgery with
appropriate margins is the preferred primary therapy. The current study data do
not support the use of adjuvant radiotherapy for patients with adequately
resected disease. Patients with stromal overgrowth, particularly when the tumor
size was > 5 cm, were found to have a high rate of distant failure; such patients
merit consideration of a trial that examines the efficacy of systemic therapy.
PMID- 11013365
TI - Fiberoptic ductoscopy for patients with nipple discharge.
AB - BACKGROUND: Breast carcinoma and precancer are thought to start in the lining of
the milk duct or lobule, yet until recently, we have not had direct access to
this area other than by blindly removing tissue by core biopsy or fine-needle
aspiration. Fiberoptic ductoscopy (FDS) is an emerging technique allowing direct
visual access to the ductal system of the breast through nipple orifice
exploration. METHODS: We applied ductoscopy to 259 women who had nipple
discharge, and we analyzed the visual findings, the cytological washings, and the
subsequent histopathology. RESULTS: In 92 (36%) of these women, fiberoptic
ductoscopy was successful in detecting an intraductal papillary lesion. Of these
observed lesions, 68 (74%) were single papilloma, 21 (23%) were multiple discrete
papillomas, and 3 (3%) were diffuse intraductal thickening which corresponded to
diffuse papillomatosis on histopathological analysis. The overall positive
predictive value of FDS screening was 83%. Of the lesions observed, 29.8% were
located in the main (segmental) duct, 43.9% lesions in the first branch, 17.5%
lesions in the second branch, 7.9% in the third branch, and 0.9% in the fourth
branch. These lesions had an overall average distance of 2.7 cm from the nipple
orifice. Ductal washings performed at the time of ductoscopy were effective at
obtaining representative exfoliated ductal cells which could be evaluated for the
presence of clumps (> 50 cells), clumps with atypia or single ductal cells. The
presence of clumps with positive FDS increased the positive predictive value to
86%. CONCLUSIONS: Fiberoptic ductoscopy currently offers a safe alternative to
ductography in guiding subsequent breast surgery in the treatment of nipple
discharge.
PMID- 11013366
TI - Preservation of the saphenous vein during inguinal lymphadenectomy decreases
morbidity in patients with carcinoma of the vulva.
AB - BACKGROUND: Traditional inguinal lymphadenectomy includes the removal of a
portion of the saphenous vein. The authors hypothesized that preserving the
saphenous vein would decrease morbidity without affecting treatment outcome.
METHODS: A retrospective review of 83 patients with carcinoma of the vulva who
underwent inguinal lymphadenectomy between 1990-1998 was performed. Postoperative
short term and long term complications were evaluated. RESULTS: A total of 139
inguinal dissections were performed in 83 patients. The saphenous vein was
preserved in 62 patients and ligated in 77 patients. The clinical characteristics
of the patients, the operating time, and the estimated blood loss were not
significantly different between the two groups. The incidence rate of short term
complications including fever, seroma, phlebitis, lymphocyst, and deep venous
thrombosis also was similar. Cellulitis occurred in 39% of the patients who
underwent vein ligation compared with 18% of the patients who underwent a vein
sparing procedure (P = 0.006). Short term (< 6 months) lower extremity lymphedema
occurred in 70% of the vein-ligated group compared with 32% of the vein-spared
group (P < 0. 001). Chronic edema (>/= 2 years) was present in only 3% of the
patients who underwent saphenous vein preservation compared with 32% of those who
underwent vein ligation (P = 0.003). Chronic lymphedema in the vein-spared group
was observed in only one patient who received postoperative radiation. Overall,
individuals with preservation of the saphenous vein were less likely to develop
complications (56% vs. 23%; P < 0.001). There was no difference in the rate of
incidence of recurrent disease between the two groups. CONCLUSIONS: Preservation
of the saphenous vein during inguinal lymphadenectomy reduces both the short term
and long term postoperative complications without affecting treatment outcome.
The saphenous vein should be preserved routinely in patients undergoing inguinal
lymphadenectomy.
PMID- 11013367
TI - High growth fraction at 9 grays of radiotherapy is associated with a good
prognosis for patients with cervical squamous cell carcinoma.
AB - BACKGROUND: MIB-1, a murine monoclonal antibody, recognizes the Ki-67 antigen of
routinely processed paraffin sections after microwave treatment. Cycling cells
are positive for MIB-1 in their nucleus, and quiescent cells are negative for MIB
1. The MIB-1 labeling index represents the growth fraction of the cell
population. METHODS: A total of 150 cervical biopsy specimens were taken from 75
consecutive patients with cervical squamous cell carcinomas before radiotherapy
(RT) and at 9 grays (Gy) of RT and were investigated to analyze the correlation
between the MIB-1 labeling index or the deltaMIB-1 labeling index and patient
prognosis or local disease control. The deltaMIB-1 index was calculated as the
MIB-1 index at 9 Gy minus the MIB-1 index before RT. RESULTS: The mean MIB-1
index was 38% (range, 11-67%) before RT and 54% (range, 15-85%) at 9 Gy. The MIB
1 index at 9 Gy was related to prognosis, including overall survival (P = 0.025),
disease free survival (P = 0. 024), and metastasis free survival (P = 0.045).
Patients who had a deltaMIB-1 index > 20% showed a trend toward a higher disease
free survival rate compared with patients who had a deltaMIB-1 index < 20% (P =
0.093). Neither the MIB-1 index nor the deltaMIB-1 index was associated with
local disease control. CONCLUSIONS: The high growth fraction at 9 Gy is regarded
as a predictive factor for a good prognosis in patients with cervical squamous
cell carcinoma patients who undergo RT alone.
PMID- 11013368
TI - A model for predicting surgical outcome in patients with advanced ovarian
carcinoma using computed tomography.
AB - BACKGROUND: A reliable model for predicting the outcome of primary cytoreductive
surgery may be a useful tool in the clinical management of patients with advanced
epithelial ovarian carcinoma. METHODS: Forty-one women with a preoperative
computed tomographic (CT) scan of the abdomen and pelvis and a histologic
diagnosis of Stage III or IV epithelial ovarian carcinoma following primary
surgery performed by one of nine gynecologic oncologists were identified from
tumor registry databases. All CT scans were analyzed retrospectively using a
panel of 25 radiographic features without knowledge of the operative findings.
Patient demographics, surgical findings and outcome, Gynecologic Oncology Group
performance status, and pre-operative serum CA125 values were collected from
patient medical records. Residual disease measuring < or = 1 cm in maximal
diameter was considered an optimal surgical result. Sensitivity, specificity,
positive predictive value (PPV), and negative predictive value (NPV) were
calculated for each radiographic feature and clinical characteristic. Based on
statistical probability of each factor predicting cytoreductive outcome, 13
radiographic features, in addition to performance status, were selected for
inclusion in the final model. Each parameter was assigned a numeric value based
on the strength of statistical association, and a total Predictive Index score
was tabulated for each patient. Receiver operating characteristic (ROC) curve
analysis was used to assess the ability of the model to predict surgical outcome.
Statistical significance was evaluated using the Fisher exact test. RESULTS:
Twenty of 41 patients (48.8%) underwent optimal cytoreduction to = 1 cm
residual disease. CT features of peritoneal thickening, peritoneal implants (>/=
2 cm), bowel mesentery involvement (>/= 2 cm), suprarenal paraaortic lymph nodes
(>/= 1 cm), omental extension (spleen, stomach, or lesser sac), and pelvic
sidewall involvement and/or hydroureter were most strongly associated with
surgical outcome. Using the Predictive Index scores, a receiver operating
characteristic curve was generated with an area under the curve = 0. 969 +/-
0.023. In the final model, a Predictive Index score >/= 4 had the highest overall
accuracy at 92.7% and identified patients undergoing suboptimal surgery with a
sensitivity of 100% (21/21). The specificity, or ability to identify patients
undergoing optimal surgery, was 85.0% (17/20). The PPV of a Predictive Index
score >/= 4 was 87.5% (21/24), and the NPV was 100%. The ability of this model to
correctly predict surgical outcome was statistically significant (P < 0.001).
CONCLUSIONS: In this model, a Predictive Index score >/= 4 demonstrated high
sensitivity, specificity, PPV, and NPV, and was highly accurate in identifying
patients with advanced epithelial ovarian carcinoma unlikely to undergo optimal
primary cytoreductive surgery. The Predictive Index model may have clinical
utility in guiding the management of patients with ovarian carcinoma.
PMID- 11013369
TI - Noninvasive, microinvasive, and invasive mucinous carcinomas of the ovary: a
clinicopathologic analysis of 40 cases.
AB - BACKGROUND: Whether ovarian mucinous tumors with epithelial stratification of
more than three cell layers in the absence of stromal invasion (i.e., carcinomas
diagnosed according to the Hart and Norris criteria) should be placed in the same
category as mucinous tumors with stromal invasion (i.e., unquestionable
carcinomas) remains controversial. Because individual mucinous tumors frequently
contain benign, borderline, and malignant components, the adequacy of sampling
has been emphasized. METHODS: We examined 21 mucinous carcinomas with no
destructive stromal invasion (MCNI), 4 mucinous carcinomas with microinvasion
(MCMI) of < 2 mm, and 15 mucinous carcinomas with invasion (MCI) of > or = 2 mm.
Tumors were diagnosed as MCNI according to Hart and Norris criteria (12 tumors)
or when severe nuclear atypia was present (9 tumors). Cases of MCNI were selected
for review if a section had been taken for each 2 cm or less of the tumor's
greatest diameter. The International Federation of Gynecology and Obstetrics
stage and follow-up data of each case were examined, and differences among MCNI,
MCMI, and MCI were analyzed. RESULTS: All 21 patients with MCNI and all 4
patients with MCMI had Stage I disease; there was no recurrence or death in these
cases. In contrast, 7 of 15 patients with MCI had Stage II or III disease, and 8
patients died. CONCLUSION: MCNI clearly should be distinguished from MCI and be
classified as noninvasive carcinomas after the absence of destructive stromal
invasion has been confirmed by examining a sufficient number of sections.
PMID- 11013370
TI - Paclitaxel, cisplatin, and epirubicin first-line chemotherapy in stage III and IV
ovarian carcinoma: long-term results of a phase II study.
AB - BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has
become the preferred chemotherapy regimen in the treatment of epithelial ovarian
carcinoma. Anthracyclines also have activity in this disease. We conducted a
Phase II study by using the combination of paclitaxel, cisplatin, and epirubicin
for the treatment of advanced ovarian carcinoma. METHODS: Forty consecutive
patients with optimally (n = 7) or suboptimally (n = 33) debulked advanced
ovarian carcinoma (International Federation of Gynecology and Obstetrics (FIGO)
Stage III or IV) were treated with paclitaxel, 135 mg/m(2), as a 3-hour
intravenous infusion, cisplatin 75 mg/m(2) intravenously (i.v.), and epirubicin
50 mg/m(2) i.v. every 3 weeks on an outpatient basis. Granulocyte-colony
stimulating factor was administered at a dose of 5 microg/kg/day on Days 5-9.
RESULTS: Among 28 patients with measurable disease, 24 (86%%) achieved an
objective response including 19 complete and 5 partial responses. Among 18
patients who underwent reassessment laparotomy, pathologic complete response was
confirmed in 9 patients. At a minimum follow-up of 40 months, the median overall
survival had not been reached whereas the median time to progression for all
patients was 18.7 months. The median remission duration for women with measurable
disease who responded to treatment was 14 months. The treatment was well
tolerated without toxic deaths; the most common toxicity was Grade 3/4
neutropenia that occurred in 30% of patients. Significant neuropathy (Grade 2 or
higher) developed in only 8% of patients. CONCLUSIONS: The combination of
paclitaxel, cisplatin, and epirubicin is a well tolerated outpatient regimen with
significant activity in the treatment of advanced epithelial ovarian carcinoma.
PMID- 11013371
TI - The clinical value of serum concentrations of cancer antigen 125 in patients with
primary fallopian tube carcinoma: a multicenter study.
AB - BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare disease, and data
on the serum concentration of tumor marker cancer antigen 125 (CA 125) in
patients with this disease are sparse. The authors assessed the clinical value of
the serum concentration of CA 125 as a prognostic and monitoring marker in
patients with surgically treated PFTC. METHODS: In a multicenter study, the
concentration of CA 125 was measured in 406 serum samples from 53 patients with
PFTC. The results were correlated with clinical data. RESULTS: The pretreatment
median serum CA 125 level was 183 U/mL (range, 6.5-5440.0 U/mL) in patients with
PFTC. In a univariate Cox regression model, tumor stage and serum CA 125 level
were associated significantly with shortened disease free survival (P = 0.006 and
P < 0.001, respectively) and with overall survival (P = 0.03 and P = 0. 001,
respectively). Lymph node involvement, tumor grade, and patient age were not
associated with the length of survival. A multivariate Cox regression model
showed that pretreatment the serum CA 125 level was a prognostic factor of
disease free and overall survival, independent of tumor stage (P = 0.005 and P =
0.01, respectively). The pretreatment serum CA 125 level was correlated with
tumor stage (P < 0.001) but not with lymph node involvement (P = 0.8), histologic
grade (P = 0.3), or patient age (P = 0.2). The serum CA 125 level during
chemotherapy was correlated significantly with Gynecologic Oncology Group
response criteria to chemotherapy (P = 0. 001). During the follow-up of patients,
serum CA 125 levels reached sensitivity, specificity, positive predictive value,
and negative predictive value of 92%, 90%, 67%, and 98%, respectively, for
differentiating between no evidence of disease and the presence of recurrent
disease. In 90% of the patients, an increase of serum CA 125 level preceded the
clinical or radiologic diagnosis of recurrent disease with a median lead time of
3 months (range, 0.5-7.0 months). CONCLUSIONS: This is the largest study to date
with respect to serum CA 125 levels in patients with PFTC. The current data
indicate that the pretreatment serum CA 125 level is an additional independent
prognostic factor of disease free and overall survival in patients with PFTC. The
serum CA 125 level adequately defines the response to chemotherapy and displays
good sensitivity and specificity characteristics during the follow-up of patients
with PFTC.
PMID- 11013372
TI - Protracted survival after resection of metastatic uveal melanoma.
AB - BACKGROUND: The objective of this study was to evaluate the usefulness of
resection of metastatic uveal melanoma and to analyze the characteristics of
patients who may benefit from surgical intervention. PATIENTS AND METHODS Twelve
patients underwent surgical removal of metastasis between 1976 and 1998. Data
regarding primary uveal melanoma, systemic metastasis, surgical procedures, and
outcomes were reviewed retrospectively. RESULTS: There were seven patients with
liver metastases, two with lung metastases, one with brain metastasis, and two
patients with metastases in the liver and other organs. Median time to systemic
metastasis was 8 years. Seven of 12 patients were asymptomatic when they were
found to have metastasis. Ten patients underwent complete resection of
metastasis. No significant surgical complications were experienced. Median
recurrence free and overall survival periods after complete resection were 19
months (range, 6-78 months) and greater than 27 months (range, 11-86 months),
respectively. Recurrence free and overall 5-year survival rates of those patients
were 15.6% and 53.3%, respectively. Three of these patients had no further
systemic recurrence. All patients whose time to systemic metastasis was within 5
years developed further systemic recurrence within 2 years after surgery. In
contrast, in 8 patients whose time to systemic metastases was greater than 5
years, 4 patients either were recurrence free or developed second metastasis more
than 4 years after surgery. CONCLUSIONS: Complete surgical removal of metastatic
uveal melanoma provided unexpectedly long survival without significant morbidity
for the selected patients. These results are encouraging and justify a trial in
which patients eligible for resection are randomized between standard treatment
and surgery.
PMID- 11013374
TI - Schwannoma with angiosarcoma. Report of a case and comparison with other types of
nerve tumors with angiosarcoma.
AB - BACKGROUND: Schwannoma with angiosarcomatous change is a rare tumor, the clinical
characteristics of which have not been analyzed. METHODS: A patient with
schwannoma with angiosarcoma arising in the midneck and clinically mimicking a
carotid body paraganglioma is described with a literature review of all
previously reported cases and a comparison of their clinical features with those
of schwannoma with conventional malignant transformation and cases of
neurofibroma and malignant peripheral nerve sheath tumor (MPNST) with
angiosarcoma. RESULTS: There are four reported cases, including the present case.
Schwannoma with angiosarcoma affects older adults, mainly men. Three tumors arose
from the vagus nerve in the neck. Three of the four angiosarcomas were
epithelioid in type. Treatment in all cases was surgical resection followed by
radiation and chemotherapy in one case and by radiation alone in another. One
patient died with residual local angiosarcoma 5 months after the diagnosis. The
remaining three patients were alive and disease free at 27 months, 43 months, and
90 months, with distant metastasis (after 15 months) reported only in the patient
described in this case report. CONCLUSIONS: Schwannoma with angiosarcoma should
be included in the differential diagnosis of presumed carotid body
paragangliomas. Like angiosarcoma alone and schwannoma with conventional
malignant transformation, but unlike cases of neurofibroma and MPNST with
angiosarcoma, the patients are older adults, and there is a male prevalence.
Schwannoma with angiosarcoma is capable of local spread with a fatal outcome and
of distant metastasis, but follow-up strongly suggests that these patients have a
better prognosis than patients with neurofibroma or MPNST with angiosarcoma.
Recommended treatment is attempted complete surgical resection followed by
radiation therapy and chemotherapy, if it can be tolerated by the patient.
PMID- 11013373
TI - A clinicopathologic reappraisal of brain stem tumor classification.
Identification of pilocystic astrocytoma and fibrillary astrocytoma as distinct
entities.
AB - BACKGROUND: Brain stem tumors in children have been classified pathologically as
low grade or high grade gliomas and descriptively as diffuse gliomas, intrinsic
gliomas, midbrain tumors, tectal gliomas, pencil gliomas, dorsal exophytic brain
stem tumors, pontine gliomas, focal medullary tumors, cervicomedullary tumors,
focal gliomas, or cystic gliomas. METHODS: To search for a simplified and
prognostic clinicopathologic scheme for brain stem tumors, the authors reviewed a
consecutive cohort of patients younger than age 21 years with tumors diagnosed
from 1980 through 1997. Pathology specimens and neuroimaging were classified by
masked review. Statistical and survival analysis along with Cox proportional
hazards regression was performed. RESULTS: Seventy-six patients were identified,
with initial diagnostic magnetic resonance imaging available for 51 and pathology
specimens for 48 patients. Twenty cases were classified histologically as
pilocytic astrocytoma (PA), 14 as fibrillary astrocytoma (FA), and 14 as other
tumors or indeterminate pathology. For all tumors, characteristics significantly
associated with a worse survival rate were: symptom duration less than 6 months
before diagnosis (P = 0.004); abducens palsy at presentation (P < 0.0001);
pontine location (P = 0.0002); and engulfment of the basilar artery (P = 0.006).
Pilocytic astrocytoma was associated with location outside the ventral pons (P =
0.001) and dorsal exophytic growth (P = 0.013); Fibrillary astrocytoma was
associated with symptoms less than 6 months (P = 0. 006), abducens palsy (P <
0.001), and engulfment of the basilar artery (P = 0.002). Pilocytic astrocytoma
showed 5-year overall survival (OS) of 95% (standard error [SE], 5%) compared
with FA 1-year OS of 23% (SE, 11%;P < 0.0001). CONCLUSIONS: Brain stem tumors can
be succinctly and better biologically classified as diffusely infiltrative brain
stem gliomas-generally FA located in the ventral pons that present with abducens
palsy, often engulf the basilar artery, and carry a grim prognosis-and focal
brain stem gliomas-frequently PA arising outside the ventral pons, often with
dorsal exophytic growth, a long clinical prodrome, and outstanding prognosis for
survival. Our findings emphasize the individuality of PA as a distinct
clinicopathologic entity with an exceptional prognosis.
PMID- 11013375
TI - Malignant lymphoma in southern Taiwan according to the revised European-American
classification of lymphoid neoplasms.
AB - BACKGROUND: The purpose of the current study was to determine the distribution
and relative frequency of each subtype of malignant lymphoma in southern Taiwan
according to the revised European-American classification of lymphoid neoplasms
(REAL). METHODS: The pathology files of a regional hospital in southern Taiwan
for 1989-1998 were searched for malignant lymphoma, lymphoproliferative disorder,
and Hodgkin disease (HD). The results of light microscopy, immunohistochemistry,
and in situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were
correlated with clinical findings, and all cases were classified according to
REAL. RESULTS: A total of 205 cases were analyzed retrospectively. There were 197
cases (96.1%) of non-Hodgkin lymphoma (NHL) and 8 cases (3. 9%) of HD. Among the
197 NHL cases, 161 (81.7%) were of B-cell lineage and 36 (18.3%) were of T
/natural killer cell lineage. Diffuse large B-cell lymphoma, extranodal marginal
zone lymphoma, and follicular lymphoma were the most common B-cell subtypes and
represented 47.2%, 19.3%, and 6.1%, respectively, of all NHL cases. Among the 36
cases of T-/natural killer cell lineage, unspecified peripheral T-cell lymphoma
(8.6%), T-/natural killer cell lymphoma (angiocentric lymphoma) (4.1%), and
anaplastic large cell lymphoma (3.6%) were the most common subtypes. Seven of
eight T-/natural killer cell lymphoma cases were positive for EBER. The eight
cases of HD were classified as lymphocyte-rich classic (two cases), nodular
sclerosis (two cases), and mixed cellularity (four cases) subtypes. Three of
these eight cases were positive for EBER. CONCLUSIONS: To the authors' knowledge
this study is the first in Taiwan using the REAL classification and it again
confirms the different geographic distribution of the various subtypes of
malignant lymphoma. The frequency of T-/natural killer cell lineage NHL in Taiwan
is higher than that in Western countries but not as high as reported previously.
PMID- 11013376
TI - Breast and cervical carcinoma mortality among women in the Appalachian region of
the U.S., 1976-1996.
AB - BACKGROUND: Previous studies have shown high cervical carcinoma mortality and
increasing breast carcinoma mortality in the Appalachian region of the U.S.
(which includes parts of 12 states and all of West Virginia). In the current
study the authors report trends in breast and cervical carcinoma death rates
among women in Appalachia for 1976-1996. METHODS: Death rates were calculated
from information provided on death certificates and reported to the National
Center for Health Statistics for Appalachian women and for women living elsewhere
in the U.S. ("other U.S. women"). Trends were examined with joinpoint regression
techniques overall and by age and race. Average annual mortality rates were
calculated by state for 1992-1996 for each state's Appalachian and non
Appalachian areas. RESULTS: Overall breast carcinoma mortality was lower among
Appalachian women than among other U.S. women throughout the study period;
however, after rates decreased among both groups in the 1990s, the difference
appears to have narrowed. No such decline was observed for women age >/= 70
years. Overall cervical carcinoma mortality was higher among Appalachian women
than among other U.S. women but decreased during the study period to rates closer
to those for other U.S. women. No significant decrease was observed among women
age < 50 years. Overall, for both black and white women, breast carcinoma
mortality was lower and cervical carcinoma mortality higher among women in
Appalachia compared with their counterparts elsewhere in the U.S. For both breast
and cervical carcinoma, the average annual death rates (1992-1996) varied by
geographic areas within the Appalachian states, but most differences were not
significant. CONCLUSIONS: Analysis of mortality trends in breast and cervical
carcinoma may provide guidance for prevention and control activities to reduce
premature mortality from these diseases.
PMID- 11013377
TI - Therapeutic use of interferon-alpha for lymphomatoid papulosis.
AB - BACKGROUND: Lymphomatoid papulosis is a primary cutaneous, CD30 positive
lymphoproliferative disorder with the potential to transform into systemic,
malignant lymphoma. Therapeutic strategies for patients with lymphomatoid
papulosis have been designed to prevent transformation but have proved to be
either inefficacious or limited by side effects. METHODS: The authors compared
the clinical, histologic, and immunohistochemical features from a group of five
patients receiving interferon-alpha (IFN-alpha) subcutaneously three times per
week with the same features from a group of six patients receiving conventional
therapy, including photochemotherapy, antibiotics, topical corticosteroids, or
surgery, in an open trial. RESULTS: In the IFN-alpha group, four patients showed
a complete remission, and one patient showed a partial remission within a time
period of 6 weeks. Two patients developed disease recurrences after
discontinuation of short term IFN-alpha therapy (5-7 months). Thereof, one
patient went into stable remission after long term IFN-alpha therapy (17 months),
and one patient remains in partial remission. In the control group, one patient
went into spontaneous remission, two patients showed partial remission, of which
one patient developed progressive disease at a later time point, whereas three
patients have recurrent disease despite of treatment. CONCLUSIONS: The current
results indicate that the treatment with IFN-alpha of patients with lymphomatoid
papulosis alters the clinical course of the disease with fewer side effects than
previous regimens; however, short term treatment does not induce stable
remission. Therefore, prolonged treatment appears to be warranted for these
patients.
PMID- 11013378
TI - Prophylactic action of oral fluconazole against fungal infection in neutropenic
patients. A meta-analysis of 16 randomized, controlled trials.
AB - BACKGROUND: Fluconazole is used widely for fungal prophylaxis. Although studies
with bone marrow transplantation (BMT) recipients clearly showed the usefulness
of oral fluconazole, results of the studies in neutropenic patients other than
BMT recipients have been inconsistent. Therefore, the authors performed a meta
analysis to evaluate the efficacy of fluconazole prophylaxis during chemotherapy
induced neutropenia. METHODS: The authors identified reports that were not
restricted to those in English and not restricted to published trials through
MEDLINE, CANCERLIT, or the data base of the Pfizer company. The authors included
prospective, randomized studies comparing oral fluconazole with placebo, no
treatment, or oral polyenes as prophylaxis for fungal infections in neutropenic
patients. Two independent authors extracted data from 16 trials with 3734
patients enrolled. The outcome measures were the development of fungal-related
death, systemic and superficial fungal infections, the use of empiric intravenous
amphotericin-B, and infections or colonization with fluconazole-resistant fungi.
The summarized odds ratios (ORs) were calculated using the Mantel-Haenszel method
and the DerSimonian-Laird method. RESULTS: Prophylactic fluconazole was not
effective in reducing fungal-related death or in reducing proven, systemic fungal
infections in non-BMT patients (OR, 0.91; 95% confidence interval [CI], 0.30-2.82
and OR, 0.85; 95% CI, 0.47-1.55, respectively). However, fluconazole was very
effective in reducing superficial fungal infections (OR, 0.44; 95% CI, 0.24
0.80), even when it was given in lower doses (50-200 mg per day). There was no
increase in proven, systemic infection of fluconazole-resistant fungi, although
colonization of those fungi increased. When the results were combined in studies
in which the incidence of systemic fungal infections was > 15%, fluconazole was
effective in reducing such infections (OR, 0.23; 95% CI, 0.15-0.36). CONCLUSIONS:
The current analyses failed to find an effect of fluconazole on both fatal fungal
infection and systemic fungal infection in non-BMT patients. Further studies on
severely neutropenic patients are warranted because prophylactic fluconazole
seemed to be effective when the incidence of systemic fungal infection was
expected to be > 15%.
PMID- 11013379
TI - Usefulness of positron emission tomographic visualization for examination of in
vivo susceptibility to metastasis.
AB - BACKGROUND: Immune surveillance may play a role in protecting against the
establishment of metastasis. The authors previously observed that the injection
of as few as 10(4) lung metastatic B16BL6 melanoma cells/0.2 mL resulted in no
metastasis and in a reduced rate of cell accumulation in the lung, the target
organ. In the current study, the authors examined the correlation between
metastatic potential and tumor cell trafficking by using a liver-metastatic
model. METHODS: The liver-metastatic potential of RAW117-H10 cells was examined
by varying the number of cells injected into mice through the portal vein. To
investigate the trafficking of the cells, the authors performed positron emission
tomography (PET) analysis, because advances in this technology now enable the use
of PET to investigate the real-time trafficking of as few as 10(4) cells/0.2 mL.
Furthermore, to clarify the role of the immune defense system, metastatic
potential and cell trafficking also were examined by using macrophage-depleted
mice. RESULTS: When 10(6) or 10(5) RAW117-H10 cells/0.2 mL were injected into
mice, both quantities of cells caused liver metastasis, cells accumulated in the
liver at a similar rate, and there was an approximately 10-fold difference in the
number of accumulated cells between the two doses. However, the injection of
10(4) cells/0.2 mL did not produce metastasis, and the accumulation rate in the
liver was less than one-tenth of that after the injection of 10(5) cells/0.2 mL.
The treatment of mice with 2-chloroadenosine for depleting macrophages prior to
the injection of 10(4) cells/0.2 mL resulted in the suppression of the fast
elimination of the cells from the liver. Corresponding to this change in PET
images, the injection of 10(4) cells/0.2 mL into 2-chloroadenosine-pretreated
mice resulted in metastasis. CONCLUSIONS: The current study suggests that immune
surveillance suppresses accumulation of tumor cells to the target and suppresses
metastasis, and this effect is obvious when small numbers of tumor cells are used
for the challenge. Furthermore, the immune defense system plays a role in the
early stage of the metastatic process.
PMID- 11013380
TI - Assessing symptom distress in cancer patients: the M.D. Anderson Symptom
Inventory.
AB - BACKGROUND: The purpose of this project was to develop the M. D. Anderson Symptom
Inventory (MDASI), a brief measure of the severity and impact of cancer-related
symptoms. METHODS: A list of symptoms was generated from symptom inventories and
by panels of clinicians. Twenty-six symptoms and 6 interference items were rated
by a validation sample of 527 outpatients, a sample of 30 inpatients from the
blood and bone marrow transplantation service, and a cross-validation sample of
113 outpatients. Clinical judgment and statistical techniques were used to reduce
the number of symptoms. Reliability, validity, and sensitivity of the MDASI were
examined. RESULTS: Cluster analysis, best subset analysis, and clinical judgment
reduced the number of symptoms to a "core" list of 13 that accounted for 64% of
the variance in symptom distress. Factor analysis demonstrated a similar pattern
in both outpatient samples, and two symptom factors and the interference scale
were reliable. Expected differences in symptom pattern and severity were found
between patients with "good" versus "poor" performance status and between
patients in active therapy and patients who were seen for follow-up. Patients
rated fatigue-related symptoms as the most severe. Groups of patients classified
by disease or treatment had severe symptoms that were not on the "core" list.
CONCLUSIONS: The core items of the MDASI accounted for the majority of symptom
distress reported by cancer patients in active treatment and those who were
followed after treatment. The MDASI should prove useful for symptom surveys,
clinical trials, and patient monitoring, and its format should allow Internet or
telephone administration.
PMID- 11013382
TI - Treatment of atrophoderma of Pasini and Pierini-associated hyperpigmentation with
the Q-switched alexandrite laser: a clinical, histologic, and ultrastructural
appraisal.
AB - BACKGROUND AND OBJECTIVE: Atrophoderma of Pasini and Pierini (APP) is an uncommon
cutaneous disorder, with no known effective treatment, manifested by
hyperpigmented patches that appear to be depressed compared with surrounding
skin. This study investigated the effectiveness of the Q-switched alexandrite
laser on a patient with extensive APP, and evaluated histopathologic and
ultrastructural changes. STUDY DESIGN/MATERIALS AND METHODS: A man with stable
APP underwent Q-switched alexandrite laser treatment to a patch on the trunk.
Biopsies were obtained from treated and untreated sites of involvement. Light and
transmission electron microscopic evaluation was performed to investigate
melanosome number, size, and volume, as well as melanin granule number and size.
RESULTS: After three treatment sessions, the treated area showed marked clinical
improvement. Electron microscopy showed a 19% reduction in melanin granule number
and size and a 65% reduction in melanosome number, size, and volume in larger
melanosomes in treated compared with untreated sites. CONCLUSION: Treatment of
APP with the Q-switched alexandrite laser results in clinical improvement.
Electron microscopic evaluation suggests that the mechanism may be a reduction in
the number, size, and volume of larger melanosomes as well as a decrement in
melanin granule number and size.
PMID- 11013381
TI - Optic nerve sheath fenestration with a novel wavelength produced by the free
electron laser (FEL).
AB - BACKGROUND AND OBJECTIVE: To determine whether 6.45-microm free electron laser
(FEL) energy can successfully perform optic nerve sheath fenestration and to
compare the acute and chronic cellular responses with this surgery. STUDY
DESIGN/MATERIALS AND METHODS: Optic nerve sheath fenestration was performed in
rabbits by using either FEL energy (< 2.5 mJ, 10 Hz, 325-microm spot size) or a
knife. The optic nerve integrity and glial response were evaluated histologically
acutely or 1 month postoperatively. RESULTS: The FEL at low energy effectively
cut the optic nerve sheaths with minimal reaction in the underlying nerve. With
FEL or knife surgical techniques, a mild astrocytic hypertrophy only adjacent to
the fenestration was observed acutely in the glial fibrillary acidic protein
(GFAP) -immunoreacted sections. The chronic healing responses after either
technique appeared similar with: (1) a thin fibrous scar at the fenestration
site, (2) cells uniformly distributed (hematoxylin and eosin), and (3) up
regulation of GFAP and S100beta in astrocytes adjacent to the fenestration site.
CONCLUSION: The FEL at low energy performs an optic nerve sheath fenestration in
a small space with ease. Both FEL and knife incisions cause a similar rapid glial
response near the fenestration site that remains 1 month later.
PMID- 11013383
TI - Effect of Nd:YAG radiation at millisecond pulse duration on dentine crater depth.
AB - BACKGROUND AND OBJECTIVE: The effect of laser parameters on laser-dentine
interaction has not been explored fully. This in vitro study investigated the
effect on dentine crater depth of Nd:YAG laser radiation with varying repetition
rates, total delivered energy, and dentine site either dyed or undyed. STUDY
DESIGN/MATERIALS AND METHODS: One hundred forty-four caries-free third molars
were sectioned transversely to provide 288 upper and lower cut surfaces. The
upper surfaces were dyed (IR5). These upper and lower cut surfaces were exposed
to an Nd:YAG laser with a 7 millisecond (msec) pulse duration, pulse repetition
rates (RR) of 2. 5, 5.4, and 10.5 Hz, and four total energies (2.28, 2.64, 3.6,
4.2 joules). Dentine crater depth was measured by using a Reflex microscope.
Results were statistically analysed with analysis of variance. RESULTS: Crater
depth increased with increase in total delivered energy and in dyed and inner
dentine sites (P<0.0001) but decreased with increasing repetition rate (P<
0.0001). CONCLUSIONS: Increasing energy, dyed, and inner dentine sites produced
deeper craters.
PMID- 11013384
TI - Optimal light dose for interstitial photodynamic therapy in treatment for
malignant brain tumors.
AB - BACKGROUND AND OBJECTIVE: The primary goal was to determine the maximal tolerable
light dose that can be administered to patients undergoing multifiber
interstitial photodynamic therapy (PDT) of malignant brain tumors at a fixed dose
of photosensitizer. STUDY DESIGN/MATERIALS AND METHODS: Eighteen patients (12
glioblastomas, 5 anaplastic astrocytoma, and 1 malignant ependymoma) were
included in this study. The total light dose delivered to the tumor was divided
into three groups of six patients each: 1,500-3,700 J, 3,700-4,400 J, and 4,400
5,900 J. RESULTS: Five patients (all glioblastomas) demonstrated postoperative
permanent neurologic deficits. None of the patients in 1,500-3,700 J, two
patients in 3,700-4,400 J, and three patients in 4,400-5,900 J had neurologic
deficits. Glioblastomas recurred more often than anaplastic astrocytomas.
Increasing the light dose did not make a difference in local/regional control of
glioblastomas. Patients with anaplastic astrocytomas survived (mean, 493 days)
longer than patients with glioblastomas (mean, 116.5 days) after PDT. Four
patients had prolonged survival (more than a year) after PDT. CONCLUSIONS:
Increasing the total light dose delivered to the tumor increases the odds of
having a permanent neurologic deficit but does not increase survival or time to
tumor progression. There was no difference in local or marginal recurrence with
increasing light dose. Recurrent anaplastic astrocytomas tend to do better than
recurrent glioblastomas with PDT.
PMID- 11013385
TI - Significantly increased lesion size by using the near-infrared photosensitizer
5,10,15,20-tetrakis (m-hydroxyphenyl)bacteriochlorin in interstitial photodynamic
therapy of normal rat liver tissue.
AB - BACKGROUND AND OBJECTIVE: Penetration of tissues by activating light ultimately
limits the size of the lesions achievable in interstitial photodynamic therapy.
Measurements of the wavelength-dependence of tissue optical properties suggest
that substantial improvements may be possible, particularly in pigmented organs
such as the liver, by using drugs absorbing at near infrared wavelengths. STUDY
DESIGN/MATERIALS AND METHODS: In this study, the extent of light induced necrosis
with the photosensitive agents Photofrin (activated at 632 nm), meta
tetra(hydroxyphenyl)chlorin (mTHPC) (activated at 652 nm) and 5,10,15,20
tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC) (activated at 740 nm) are
compared in normal rat liver. Interstitial irradiation of mTHPBC-sensitized liver
tissue resulted in significantly larger necrotic areas than irradiation of
Photofrin and mTHPC-sensitised livers. CONCLUSION: The results illustrate the
advantage of near-infrared photosensitizer activation and point to a specific
role for mTHPBC in the interstitial treatment of liver tumours.
PMID- 11013386
TI - Time-resolved fluorescence of human aortic wall: use for improved identification
of atherosclerotic lesions.
AB - BACKGROUND AND OBJECTIVE: This study characterized aortic time-resolved
fluorescence spectra for stratified levels of atherosclerosis and proposed
interpretation of spectrotemporal variations in terms of histologic changes.
STUDY DESIGN/MATERIALS AND METHODS: Fluorescence emission transients were
measured at 370-510 nm (337 nm excitation) on 94 excised human aortic samples,
ranging from normal to advanced fibrous atherosclerotic lesion. Global analysis
yielded a three-exponential approximation of the time-resolved spectra from which
average lifetime and decay-associated spectra were derived. RESULTS: Average
lifetime at 390 nm gradually increased from 2.4+/-0.1 nsec (normal aorta) to
3.9+/-0.1 nsec (advanced lesion). Fluorescence intensity was markedly decreased
above 430 nm in intermediate and advanced lesions. Spectral intensity associated
with the intermediate decay increased at 470-490 nm for early and intermediate
lipid-rich lesions. CONCLUSION: Time-resolved fluorescence spectra of aortic
samples presented distinctive features for each atherosclerotic lesion type,
which could serve as characteristic markers for optical analysis of the aortic
wall.
PMID- 11013387
TI - In vitro effects of low-level laser irradiation at 660 nm on peripheral blood
lymphocytes.
AB - BACKGROUND AND OBJECTIVE: The effects of low-level laser light irradiation are
still highly contested, and the mechanisms of its action still unclear. This
study was conducted to test the effects of low-level laser irradiation at 660 nm
on human lymphocytes and to investigate the possible mechanisms by which these
effects are produced. STUDY DESIGN/MATERIALS AND METHODS: Whole blood obtained by
phlebotomy was irradiated at 660 nm by using energy fluences between 0 and 5.0
J/cm(2). The lymphocytes were isolated after irradiation of the whole blood. For
the control experiment, the lymphocytes were first isolated and then irradiated
at the same wavelength and energy fluence for comparison. The proliferation of
lymphocytes and the formation of free radicals and lipid peroxides were
monitored. Hemoglobin was also irradiated in a cell-free environment to test for
the production of lipid peroxides. RESULTS: Lymphocyte proliferation was
significantly higher (P<0.05) as expressed by a Stimulation Index in samples
irradiated in the presence of whole blood compared with lymphocytes irradiated
after isolation from whole blood. Free radical and lipid peroxide production also
increased significantly when samples were irradiated in the presence of red blood
cells. CONCLUSION: The present study supports the hypothesis that one mechanism
for the photobiostimulation effect after irradiation at 660 nm is the reaction of
light with hemoglobin, resulting in oxygen radical production.
PMID- 11013388
TI - New technique for producing hybridoma by using laser radiation.
AB - BACKGROUND AND OBJECTIVE: With conventional methods, cell fusion rate is
extremely low, and fusion of two specific cells is not possible. We developed a
new method for inducing cell fusion under the microscope by using a
microprocessing device by laser. STUDY DESIGN/MATERIALS AND METHODS: Under a
microscope, the target cells were irradiated with laser beams for trapping. Then,
the trapped cells were transferred and placed in contact with the corresponding
cells, which were also fixed by laser beam. The pulse laser beams are focused on
the contact surface to cut small perforations for mutual communication of the
cytoplasms. RESULTS: The fusion rate of mouse myeloma cells was 38%. The rate of
hybridoma production of myeloma cell and lymphocyte was 2%. We confirmed the
proliferation of the newly formed hybridoma in HAT medium and the production of
immunoglobulin G. CONCLUSION: This new cell fusion method is characterized by
production of hybridomas of target cells, lower cell toxicity, and a high rate of
hybrid production.
PMID- 11013389
TI - Optical-thermal simulation of human tonsillar tissue irradiation: clinical
implications.
AB - BACKGROUND AND OBJECTIVE: Mucosa intact laser tonsillar ablation is an
alternative to conventional tonsillectomy. The efficacy of this procedure was
demonstrated in canines, but establishing the safety of irradiating human tonsils
is paramount. STUDY DESIGN/MATERIALS AND METHODS: An optical-thermal simulation
of tonsillar tissue irradiation was previously developed, but the effect of
varying parameters was not investigated. The tissue response to irradiation at 5
25 watts for 1 minute and 10 watts for 10 seconds to 162 seconds is simulated.
RESULTS: At 15 watts and greater, the peak temperature is over 100 degrees C and
the mucosal temperature is over 70 degrees C. At the depth of the tonsil, the
temperature does not vary significantly. The peak temperature is at 1 mm. The
radial temperature profile is not significantly altered by longer irradiation
times. CONCLUSIONS: The optimal dosimetry parameters for irradiation of human
tonsillar tissue at 805 nm with the MILTA technique is under 15 watts for
approximately 1 minute.
PMID- 11013390
TI - Aneuploidy, the somatic mutation that makes cancer a species of its own.
AB - The many complex phenotypes of cancer have all been attributed to "somatic
mutation." These phenotypes include anaplasia, autonomous growth, metastasis,
abnormal cell morphology, DNA indices ranging from 0.5 to over 2, clonal origin
but unstable and non-clonal karyotypes and phenotypes, abnormal centrosome
numbers, immortality in vitro and in transplantation, spontaneous progression of
malignancy, as well as the exceedingly slow kinetics from carcinogen to
carcinogenesis of many months to decades. However, it has yet to be determined
whether this mutation is aneuploidy, an abnormal number of chromosomes, or gene
mutation. A century ago, Boveri proposed cancer is caused by aneuploidy, because
it correlates with cancer and because it generates "pathological" phenotypes in
sea urchins. But half a century later, when cancers were found to be non-clonal
for aneuploidy, but clonal for somatic gene mutations, this hypothesis was
abandoned. As a result aneuploidy is now generally viewed as a consequence, and
mutated genes as a cause of cancer although, (1) many carcinogens do not mutate
genes, (2) there is no functional proof that mutant genes cause cancer, and (3)
mutation is fast but carcinogenesis is exceedingly slow. Intrigued by the
enormous mutagenic potential of aneuploidy, we undertook biochemical and
biological analyses of aneuploidy and gene mutation, which show that aneuploidy
is probably the only mutation that can explain all aspects of carcinogenesis. On
this basis we can now offer a coherent two-stage mechanism of carcinogenesis. In
stage one, carcinogens cause aneuploidy, either by fragmenting chromosomes or by
damaging the spindle apparatus. In stage two, ever new and eventually tumorigenic
karyotypes evolve autocatalytically because aneuploidy destabilizes the
karyotype, ie. causes genetic instability. Thus, cancer cells derive their unique
and complex phenotypes from random chromosome number mutation, a process that is
similar to regrouping assembly lines of a car factory and is analogous to
speciation. The slow kinetics of carcinogenesis reflects the low probability of
generating by random chromosome reassortments a karyotype that surpasses the
viability of a normal cell, similar again to natural speciation. There is
correlative and functional proof of principle: (1) solid cancers are aneuploid;
(2) genotoxic and non-genotoxic carcinogens cause aneuploidy; (3) the biochemical
phenotypes of cells are severely altered by aneuploidy affecting the dosage of
thousands of genes, but are virtually un-altered by mutations of known
hypothetical oncogenes and tumor suppressor genes; (4) aneuploidy immortalizes
cells; (5) non-cancerous aneuploidy generates abnormal phenotypes in all species
tested, e.g., Down syndrome; (6) the degrees of aneuploidies are proportional to
the degrees of abnormalities in non-cancerous and cancerous cells; (7) polyploidy
also varies biological phenotypes; (8) variation of the numbers of chromosomes is
the basis of speciation. Thus, aneuploidy falls within the definition of
speciation, and cancer is a species of its own. The aneuploidy hypothesis offers
new prospects of cancer prevention and therapy.
PMID- 11013391
TI - Stochastic simulation of processive and oscillatory sliding using a two-headed
model for axonemal dynein.
AB - Computer simulations have been used in an attempt to understand experimental
observations of processive and oscillatory sliding by one or a few axonemal
dyneins. A simple two-headed model has been examined using stochastic simulation
methods. To explain the experimental observations, the model must be capable of
taking backward steps, as well as forward steps, and there must be hysteresis in
switching between forward or backward stepping. When the effects of Brownian
movement on motor strain are included, it is not possible to obtain oscillations
as regular as the experimental records by using motor strain to regulate
switching between forward or backward stepping.
PMID- 11013392
TI - Hypophosphorylated neurofilament subunits undergo axonal transport more rapidly
than more extensively phosphorylated subunits in situ.
AB - Axonal transport of neurofilaments (NFs) has long been considered to be regulated
by phosphorylation. We present evidence that in optic axons of normal mice, the
rate of NF axonal transport is inversely correlated with the NF phosphorylation
state. In addition to 200 kDa NF-H and 145 kDa NF-M, axonal cytoskeletons from
CNS contained a range of phospho-variants of NF-H migrating between 160-200 kDa,
and of NF-M migrating at 97-145 kDa. While 160 kDa phospho-variants of NF-H have
been well characterized, we confirmed the identity of the previously-described 97
kDa species as a hypophospho-variant of NF-M since (1) pulse-chase metabolic
labeling confirmed the 97 kDa species to be a new synthesis product that was
converted by phosphorylation over time into a form migrating at 145 kDa, (2) the
97 kDa protein reacted with multiple NF-M antibodies, including one specific for
hypophosphorylated NF-M, and (3) dephosphorylation converted NF-M isoforms to 97
kDa. Autoradiographic analyses following metabolic radiolabeling demonstrated
that hypophosphorylated NF-H and NF-M isoforms underwent substantially more rapid
transport in situ than did extensively phosphorylated isoforms, while NF-H
subunits bearing a developmentally delayed C-terminal phospho-epitope transported
at a rate slower than that of total 200 kDa NF-H. Differential transport of
phospho-variants also highlights that these variants are not homogeneously
distributed among NFs, but are segregated to some extent among distinct, although
probably overlapping, NF populations, indicating that axonal NFs are not
homogeneous with respect to phosphorylation state.
PMID- 11013393
TI - Preferential incorporation of tubulin into the junctional region of ciliary outer
doublet microtubules: a model for treadmilling by lattice dislocation.
AB - Even in the presence of colchicine or Taxol(R), sea urchin embryonic cilia
undergo substantial steady-state turnover, with a rate of tubulin incorporation
approaching half that seen in full regeneration [Stephens: Mol Biol Cell 8:2187
2198, 1997]. Preliminary experiments suggest that tubulin incorporates
differentially into the most stable portion of the outer doublet, the junctional
protofilaments [Stephens: Cell Struct Funct 24:413-418, 1999]. To explore this
possibility further, embryos of the sea urchin Tripneustes gratilla, a ciliary
length inducible system [Stephens: J Exp Zool 269:106-115, 1994a], were pulse
labeled with (3)H leucine during steady-state turnover or induced elongation,
followed by regeneration in the presence of unlabeled leucine. Cilia were
isolated by hypertonic shock and fractionated into detergent-soluble membrane
plus matrix, thermally-solubilized microtubule walls, and insoluble 9-fold
symmetric remnants of A-B junctional protofilaments plus associated architectural
elements. The fractions were resolved by SDS-PAGE and the specific activity of
alpha-tubulin was determined. In cilia undergoing turnover or elongation during
an isotope pulse, the specific activity of tubulin in the junctional region
approximated that of precursor membrane plus matrix tubulin but surpassed that of
the tubule wall by a factor of approximately 1.5. In cilia regenerated during an
isotope chase, the specific activity of junctional tubulin exceeded that of both
the membrane plus matrix and the tubule wall by a similar factor. These data
indicate that tubulin is preferentially incorporated into junctional
protofilaments during steady-state turnover, induced elongation and regeneration.
A model for directional incorporation based on surface lattice discontinuities in
the outer doublet is proposed.
PMID- 11013394
TI - Centrosome-directed translocation of Weibel-Palade bodies is rapidly induced by
thrombin, calyculin A, or cytochalasin B in human aortic endothelial cells.
AB - To examine the possible role of the cytoskeleton in exocytosis of Weibel-Palade
bodies (WPBs), we used double immunofluorescence and electron microscopy to study
the spatial relationships between WPBs and main cytoskeletal elements in
endothelial cells treated with secretagogue, such as thrombin, or cytoskeleton
damaging agents. Unexpectedly, we have found that WPBs undergo rapid
translocation towards the centrosome both in cells treated with thrombin and in
those treated with cytochalasin B or calyculin A. Typically, 3 or 5 min after
agent addition compact cluster of WPBs became visible near the microtubule
organizing center (MTOC) in most endothelial cells in which a fivefold increase
in WPBs localized in close proximity to the mother centriole had been detected.
In both thrombin- and cytochalasin-treated cells that exhibit a noticeable
depletion in WPBs compared to control cells, WPBs located at the cell periphery
were found to colocalize with vimentin intermediate filaments, but not with
microtubules. In contrast, there was precise colocalization observed between WPBs
and microtubules in calyculin-treated cells in which all WPBs undergo centrosome
directed translocation within 15 min after the agent addition. When vimentin
filaments were induced to collapse to a perinuclear location by the microtubule
disrupting agent demecolcine, WPBs also translocated to the perinuclear region,
where numerous WPBs were found to be localized within the bundles of intermediate
sized filaments. The data provide the first direct evidence that secretory
granules utilize microtubule-based transport system to move in retrograde
direction, i.e., away from the plasma membrane, towards the centrosome. We
suggest that anterograde movement of WPBs is primarily dependent on their
interaction with vimentin intermediate filaments.
PMID- 11013395
TI - Association of SPARC (osteonectin, BM-40) with extracellular and intracellular
components of the ciliated surface ectoderm of Xenopus embryos.
AB - SPARC (Secreted Protein, Acidic, Rich in Cysteine) was detected by
immunohistochemistry in the sensorial layer of the bilayered embryonic epidermis
of Xenopus laevis during neurulation, when a subset of the sensorial cells are
selected to differentiate into ciliated cell precursors. After the ciliated cells
had intercalated into the outer layer and had undergone ciliogenesis, intense
SPARC immunostaining was associated with the cilia and remained associated with
the cilia throughout their persistence on the epidermis. Circumferential SPARC
immunostaining was also detected at the interface between surface epithelial
cells. Animal cap explants indicated that the embryonic activation of SPARC
expression in the dorsal ectoderm does not require signaling from factors
secreted by the underlying mesoderm. Immunoelectron microscopy revealed that
SPARC is intimately associated with the 9 + 2 microtubule arrays of cilia. Our
data indicate that SPARC plays a role in the development and function of the
surface ciliated epidermis of Xenopus embryos. We propose that the counter
adhesive activity of SPARC facilitates the intercalation of ciliary cell
precursors to the surface epithelial layer, where its Ca(2+)-binding abilities
promote cell-cell adhesion. Based on its association with ciliary microtubule
arrays, we also propose that intracellular SPARC may play a role in regulating
ciliary beat frequency and polarity.
PMID- 11013396
TI - Linear extrapolation method of analyzing solvent denaturation curves.
AB - The two most common methods of measuring the conformational stability of a
protein are differential scanning calorimetry and an analysis of solvent
denaturation curves by using the linear extrapolation method. In this article, we
trace the history of the linear extrapolation method, review how the method is
used to measure protein stability, and then discuss some of the other important
uses.
PMID- 11013397
TI - Large contributions of coupled protonation equilibria to the observed enthalpy
and heat capacity changes for ssDNA binding to Escherichia coli SSB protein.
AB - Many macromolecular interactions, including protein-nucleic acid interactions,
are accompanied by a substantial negative heat capacity change, the molecular
origins of which have generated substantial interest. We have shown previously
that temperature-dependent unstacking of the bases within oligo(dA) upon binding
to the Escherichia coli SSB tetramer dominates the binding enthalpy, DeltaH(obs),
and accounts for as much as a half of the observed heat capacity change,
DeltaC(p). However, there is still a substantial DeltaC(p) associated with SSB
binding to ssDNA, such as oligo(dT), that does not undergo substantial base
stacking. In an attempt to determine the origins of this heat capacity change, we
have examined by isothermal titration calorimetry (ITC) the equilibrium binding
of dT(pT)(34) to SSB over a broad pH range (pH 5. 0-10.0) at 0.02 M, 0.2 M NaCl
and 1 M NaCl (25 degrees C), and as a function of temperature at pH 8.1. A net
protonation of the SSB protein occurs upon dT(pT)(34) binding over this entire pH
range, with contributions from at least three sets of protonation sites (pK(a1) =
5.9-6.6, pK(a2) = 8.2-8.4, and pK(a3) = 10.2-10.3) and these protonation
equilibria contribute substantially to the observed DeltaH and DeltaC(p) for the
SSB-dT(pT)(34) interaction. The contribution of this coupled protonation (
approximately -260 to -320 cal mol(-1) K(-1)) accounts for as much as half of the
total DeltaC(p). The values of the "intrinsic" DeltaC(p,0) range from -210 +/- 33
cal mol(-1) degrees K(-1) to -237 +/- 36 cal mol(-1)K(-1), independent of [NaCl].
These results indicate that the coupling of a temperature-dependent protonation
equilibria to a macromolecular interaction can result in a large negative
DeltaC(p), and this finding needs to be considered in interpretations of the
molecular origins of heat capacity changes associated with ligand-macromolecular
interactions, as well as protein folding.
PMID- 11013398
TI - Confirmation of a unique intra-dimer cooperativity in the human hemoglobin
alpha(1)beta(1)half-oxygenated intermediate supports the symmetry rule model of
allosteric regulation.
AB - The contribution of the alpha(1)beta(1)half-oxygenated tetramer
[alphabeta:alphaO(2)betaO(2)] (species 21) to human hemoglobin cooperativity was
evaluated using cryogenic isoelectric focusing. The cooperative free energy of
binding, reflecting O(2)-driven protein structure changes, was measured as
(21)DeltaG(c) = 5.1 +/- 0. 3 kcal for the Zn/FeO(2) analog. For the Fe/FeCN
analog, (21)DeltaG(c) was estimated as 4.0 kcal after correction for a CN ligand
rearrangement artifact, demonstrating that ligand rearrangement does not
invalidate previous conclusions regarding this species. In the context of the
entire Hb cooperativity cascade, which includes eight intermediate species, the
21 tetramer is highly abundant relative to the other doubly-ligated species,
providing strong support for the previously determined consensus partition
function of O(2) binding and for the Symmetry Rule model of hemoglobin
cooperativity (Ackers et al., Science 1992;255:54-63). Cooperativity of normal
human hemoglobin is shown to depend on site-configuration, and not solely the
number of O(2) bound, nor the occupancy of alpha vs. beta subunits. Verification
of a unique contribution from the alpha(1)beta(1)doubly-oxygenated species to the
equilibrium O(2) binding curve strongly reinforces the Symmetry Rule
interpretation that the alpha(1)beta(1)dimer acts both as a structural and
functional element in cooperative O(2) binding.
PMID- 11013399
TI - Structural thermodynamics of a random coil protein in guanidine hydrochloride.
AB - An important problem in protein folding is to understand the relationship between
the structure of a denatured ensemble and its thermodynamics. Using 0 - 6M GdnHCl
at fixed pH, we evaluated dimensional changes of an extensively denatured
ensemble along with a thermodynamic parameter (Deltaupsilon) that monitors the
proton inventory of the ensemble. Reduced and carboxyamidated ribonuclease A
(RCAM) is a member of a class of disulfide-free RNase A molecules believed to be
random coils (extensively denatured) in aqueous solution. Because GdnHCl
interacts more favorably with the protein than water does, this denaturant is
observed to increase the Stokes radius of the random coil, with the greatest
Stokes radius change occurring in the 0 - 1.5M GdnHCl range. Measurement of the
degree of protonation (proton inventory) of the ensemble as a function of GdnHCl
at the fixed pH shows that the thermodynamic character of the ensemble also
changes markedly in the 0 - 1.5M GdnHCl range, but with little or no change
beyond 1.5M GdnHCl. To obtain denaturant-independent DeltaG degrees (N-D) values,
the linear extrapolation method (LEM) requires the thermodynamic character of the
native and denatured ensembles to be invariant in the transition zone. The
results reported here indicate that proteins with a transition midpoint in the 0
1.5M GdnHCl range will not give denaturant-concentration independent DeltaG
degrees (N-D) values. Such LEM-derived DeltaG degrees (N-D) quantities are a
property of the protein and the denaturant, a condition that considerably limits
their value in understanding structural energetics.
PMID- 11013400
TI - Energetics of the specific binding interaction of the first three zinc fingers of
the transcription factor TFIIIA with its cognate DNA sequence.
AB - The energetics of the specific interaction of a protein fragment (zf1-3)
containing the three N-terminal zinc fingers of the Xenopus laevis transcription
factor TFIIIA with its cognate DNA sequence, contained in a 15 bp DNA duplex were
studied using isothermal titration calorimetry (ITC), differential scanning
calorimetry (DSC) and fluorescence titration. The use of both ITC and DSC is
necessary to provide values for the thermodynamic parameters that have been
corrected for thermal fluctuations of the interacting molecules. In the
temperature range from 13 degrees C to 45 degrees C (where all the binding
reaction components are folded), formation of the complex is enthalpically driven
with a negative heat capacity effect (DeltaC(p)). In this respect, the binding
reaction of zf1-3 is similar to those of other proteins that bind in the major
groove of DNA. It is dissimilar to the association reactions of proteins,
however, that bind in the minor groove of DNA and that are driven by a dominating
entropy factor. Comparison of the experimental values of DeltaH(ass) and
DeltaC(p) with expected values of these parameters, calculated from the burial of
polar and nonpolar molecular surfaces, indicates that the polar groups at the
protein/DNA interface are not completely dehydrated upon formation of the
complex. It also seems that the expected large positive entropy of dehydration
upon forming the zfl-3/DNA complex ( approximately 1900 J * K(-1) * mol(-1))
cannot be balanced by the reduction in translational/rotational and
configurational freedom of the protein to the level of the observed entropy of
binding (38 J * K(-1) * mol(-1)). It is suggested that the additional negative
entropy contribution comes from a damping of torsional motions in the DNA duplex.
PMID- 11013401
TI - Structural stability of binding sites: consequences for binding affinity and
allosteric effects.
AB - During the course of biological function, proteins interact with other proteins,
ligands, substrates, inhibitors, etc. These interactions occur at precisely
defined locations within the protein but their effects are sometimes propagated
to distal regions, triggering highly specific responses. These effects can be
used as signals directed to activate or inhibit other sites, modulate
interactions with other molecules, and/or establish inter-molecular communication
networks. During the past decade, it has become evident that the energy of
stabilization of the protein structure is not evenly distributed throughout the
molecule and that, under native conditions, proteins lack global cooperativity
and are characterized by the occurrence of multiple independent local unfolding
events. From a biological point of view, it is important to assess if this uneven
distribution reflects specific functional requirements. For example, are binding
sites more likely to be found in well structured regions, unstable regions, or
mixed regions? In this article, we have addressed these questions by performing a
structure-based thermodynamic stability analysis of non-structurally homologous
proteins for which high resolution structures of their complexes with specific
ligands are available. The results of these studies indicate that for all 16
proteins considered, the binding sites have a dual character and are
characterized by the presence of regions with very low structural stability and
regions with high stability. In many cases the low stability regions are loops
that become stable and cover a significant portion of low molecular weight
ligands upon binding. For enzymes, catalytic residues are usually, but not
always, located in regions with high structural stability. It is shown that this
arrangement provides significant advantages for the optimization of binding
affinity of small ligands. In allosteric enzymes, low stability regions in the
regulatory site are shown to play a crucial role in the transmission of
information to the catalytic site.
PMID- 11013402
TI - Thermodynamic analysis of interactions between denaturants and protein surface
exposed on unfolding: interpretation of urea and guanidinium chloride m-values
and their correlation with changes in accessible surface area (ASA) using
preferential interaction coefficients and the local-bulk domain model.
AB - A denaturant m-value is the magnitude of the slope of a typically linear plot of
the unfolding free energy change DeltaG degrees (obs) vs. molar concentration
(C(3)) of denaturant. For a given protein, the guanidinium chloride (GuHCl) m
value is approximately twice as large as the urea m-value. Myers et al. (Protein
Sci 1995;4:2138-2148) found that experimental m-values for protein unfolding in
both urea and GuHCl are proportional to DeltaASA(corr)(max), the calculated
maximum amount of protein surface exposed to water in unfolding, corrected
empirically for the effects of disulfide crosslinks: (urea m
value/DeltaASA(corr)(max)) = 0.14+/-0.01 cal M(-1) A(-2) and (GuHCl m
value/DeltaASA(corr)(max)) = 0.28+/-0.03 cal M(-1) A(-2). The observed linearity
of plots of DeltaG degrees (obs) vs. C(3) indicates that the difference in
preferential interaction coefficients DeltaGamma(3) characterizing the
interactions of these solutes with denatured and native protein surface is
approximately proportional to denaturant concentration. The proportionality of m
values to DeltaASA(corr)(max) indicates that the corresponding DeltaGamma(3) are
proportional to DeltaASA(corr)(max) at any specified solute concentration. Here
we use the local-bulk domain model of solute partitioning in the protein solution
(Courtenay et al., Biochemistry 2000;39:4455-4471) to obtain a novel quantitative
interpretation of denaturant m-values. We deduce that the proportionality of m
value to DeltaASA(corr)(max) results from the proportionality of B(1)(0) (the
amount of water in the local domain surrounding the protein surface exposed upon
unfolding) to DeltaASA(corr)(max). We show that both the approximate
proportionality of DeltaGamma(3) to denaturant concentration and the residual
dependence of DeltaGamma(3)/m(3) (where m(3) is molal concentration) on
denaturant concentration are quantitatively predicted by the local-bulk domain
model if the molal-scale solute partition coefficient K(P) and water-solute
exchange stoichiometry S(1,3) are independent of solute concentration. We obtain
K(P,urea) = 1.12+/-0.01 and K(P,GuHCl) = 1.16+/-0.02 (or K(P,GuH+) congruent with
1.48), values which will be useful to characterize the effect of accumulation of
those solutes on all processes in which the water-accessible area of unfolded
protein surface changes. We demonstrate that the local-bulk domain analysis of an
m-value plot justifies the use of linear extrapolation to estimate ( less,
similar 5% error) the stability of the native protein in the absence of
denaturant (DeltaG(o)(o)), with respect to a particular unfolded state. Our
surface area calculations indicate that published m-values/DeltaASA ratios for
unfolding of alanine-based alpha-helical oligopeptides by urea and GuHCl exceed
the corresponding m-value/DeltaASA ratios for protein unfolding by approximately
fourfold. We propose that this difference originates from the approximately
fourfold difference (48% vs. 13%) in the contribution of polar backbone residues
to DeltaASA of unfolding, a novel finding which supports the long-standing but
not universally accepted hypothesis that urea and guanidinium cation interact
primarily with backbone amide groups. We propose that proteins which exhibit
significant deviations from the average m-value/DeltaASA ratio will be found to
exhibit significant deviations from the expected amount and/or average
composition of the surface exposed on unfolding.
PMID- 11013403
TI - Protein heat capacity reflects the dynamics of enthalpy exchange between the
single macromolecule and the surroundings.
AB - Heat capacity has played a prominent role in relating macroscopic and microscopic
properties of small molecules and crystals. However, its diagnostic power can
also be used for macromolecules such as proteins. It is shown in the present
study that the macroscopically observed protein heat capacity provides direct
access to the thermodynamic state of the single protein molecule. The new model
of the physical basis of protein heat capacity emphasizes the dynamic nature of
protein molecules. It incorporates equilibrium fluctuations as an integral
constituent and shows that the increase in the magnitude of equilibrium
fluctuations is coupled to an increase in the enthalpy flux between the
individual protein molecule and its surroundings.
PMID- 11013404
TI - Binding of small organic molecules to macromolecular targets: evaluation of
conformational entropy changes.
AB - The conformational entropy is the largest unfavorable effect that must be
overcome during protein folding and binding. Accurate predictions of protein
stability and binding affinity require a precise way of evaluating conformational
entropy changes. Previously we implemented a computational approach aimed at
estimating conformational entropy changes in peptides (D'Aquino et al., Proteins
1996;25:143-156; Lee et al., Proteins 1994;20:68-84). Here we extend this
approach to estimate conformational entropy changes in molecules of
pharmaceutical interest. Calculations were carried out for a set of 36 small
organic molecules containing one dihedral angle and different functional groups
around the central bond. Entropy changes were calculated for these molecules as
the difference between the entropy of the free molecule and the entropy of the
molecule when it is constrained to occupy a particular range of dihedrals, as in
the bound state. Entropy changes for binding of larger molecules can be estimated
assuming additivity on a per bond basis. Thus, the results presented here provide
an initial toolbox of conformational entropy values in the form of a lookup table
that can be used in the estimation of entropy changes associated with binding
processes of more complex molecules. To facilitate their use, the values were
parameterized in terms of the number and type of atoms neighboring each specific
dihedral. Both methods, lookup table and parameterized equation, provide a very
fast way of evaluating conformational entropy changes, making them suitable for
fast screening algorithms.
PMID- 11013405
TI - Induction of DNA adducts by several polychlorinated biphenyls.
AB - It is known that lower-chlorinated biphenyls are metabolically activated to
electrophilic quinoid species capable of binding to DNA. Also, certain
metabolites are capable of redox cycling, thereby increasing oxidative stress in
biological systems. In the present study, we tested mono-, di-, tri-, tetra-,
penta-, hexa-, and heptachlorinated biphenyls for their ability to bind with DNA
and to induce oxidative DNA damage. We present additional evidence that several
PCB congeners form DNA adducts after metabolic activation, which can be detected
by the nuclease P1- or butanol-enrichment procedures of the (32)P-postlabeling
technique. Butanol and nuclease P1 enrichments showed different adduct
recoveries, depending on the level of chlorination of the biphenyls. Application
of the nuclease P1 enrichment showed that the incubation of 2-chloro-; 3, 4
dichloro-; 2,4,4'-trichloro-; 3,4,5-trichloro-; and 2,2',5, 5'
tetrachlorobiphenyl with calf thymus DNA and liver microsomes from rats treated
with phenobarbital, followed by oxidation with a peroxidase, produced five to
eight different DNA adducts. For these lower-chlorinated biphenyls, butanol
enrichment generally showed a lower recovery. For some higher substituted
congeners (3,3',4,4', 5-pentachloro-, 2,2',3,4,4',5'-hexachloro-, 2,2',4,4',5, 5'
hexachloro-, and 2,2',3,4,4',5,5'-heptachlorobiphenyl), after butanol enrichment
a single dominant spot was observed, which was absent in the nuclease P1
procedure. After incubation of calf thymus DNA with either higher- or lower
chlorinated PCB congeners, we were not able to detect significantly increased
levels of oxidative DNA damage above background levels, measured as 8-oxo-7, 8
dihydro-2'deoxyguanosine. In view of the carcinogenicity of PCB mixtures in
animals and the ability of PCB metabolites to bind covalently to DNA, rats were
orally treated with a mixture of PCBs (Aroclor 1242). PCB-DNA adduct levels were
analyzed in PCB target organs: liver, thymus, glandular stomach, spleen, testes,
seminal vesicles and prostate DNA. In vivo PCB-DNA adducts could not be detected
by either the butanol- or by the NP1-enrichment procedure in rat target tissue
DNA. Also, no differences in oxidative DNA damage could be observed between PCB
treated rats and controls. These results indicate a lack of DNA reactivity of PCB
mixtures in vivo.
PMID- 11013406
TI - Effect of a dCTP:dTTP pool imbalance on DNA replication fidelity in Friend murine
erythroleukemia cells.
AB - Nucleotide pool imbalances have been reported to affect the fidelity of DNA
replication and repair in prokaryotic and eukaryotic cells. We have reported
previously that the mutagen-hypersensitive thymidine kinase (TK)-deficient Friend
erythroleukemia (FEL) cells (subclones 707BUF and 707BUE), have a more than
sixfold increase in the dCTP:dTTP pool ratio when compared to that of wild-type,
TK-positive (TK(+)) clone 707 cells. In this study we present the results of an
investigation of the effect of the dCTP:dTTP pool imbalance on the accuracy of
DNA replication within 707BUF cells. We examined the spontaneous mutation spectra
occurring at the adenine phosphoribosyltransferase (aprt) locus within clone 707
(TK(+)) and 707BUF (TK(-)) FEL cells. Mutations recovered at the aprt locus in
FEL cells comprised: base substitutions (43:73), frameshifts (14:13.5), and
deletions (43:13.5) [clone 707 (TK(+)):707BUF (TK(-)), respectively, expressed as
percentages]. A comparison of the mutation spectra obtained for the two cell
lines did not reveal any significant increase in misincorporation of dCTP, the
nucleotide in excess, in 707BUF (TK(-)) cells, during DNA replication synthesis.
These data suggest that the dCTP:dTTP pool imbalance does not alter the fidelity
of DNA replication synthesis in 707BUF (TK(-)) FEL cells. Rather, the
predominance of GC --> AT transitions (53%) in the 707BUF (TK(-)) spectrum may
reflect a reduced efficiency of repair by uracil DNA glycosylase of uracil
residues within these cells.
PMID- 11013407
TI - Cloning and expression of rat CYP2E1 in Saccharomyces cerevisiae: detection of
genotoxicity of N-alkylformamides.
AB - A cDNA coding for rat cytochrome P450 2E1 was cloned into the multicopy vector
pYeDP60 and expressed in haploid RSY6 and diploid RS112 yeast strains of
Saccharomyces cerevisiae under control of the GAL10-CYC1 promoter. Spectral and
catalytic properties of the expressed 2E1 were examined in whole cells or
microsomes of both strains. The level of CYP2E1 obtained in RS112 (200 pmol/mg
microsomal protein) was the highest among CYP2E1 produced in the various
expression systems. The monooxygenase activity in the microsomes of both strains,
measured as aniline hydroxylase, was found comparable to that of control rat
hepatic microsomes. In a reconstituted system in the presence of exogenous rat
P450 reductase, their activity increased about 10-fold. When exposed to the
carcinogen NDMA, a known 2E1 substrate, the recombination frequency determined in
the 2E1-expressing RS112 cells was enhanced, in a dose-dependent manner, up to 20
fold. The exposure of the same cells to the hepatotoxic solvents, N-methyl- and N
ethylformamide, resulted in an induction of recombination frequency, which was
not observed in the void plasmid containing RS112 cells in the presence of S9
hepatic fractions from pyrazole-induced rats, as a specific exogenous metabolic
activation system. These results demonstrate that the 2E1-expressing cells
metabolize the two N-alkylformamides to genotoxic intermediates and, therefore,
they provide an useful tool to study the bioactivation mechanism of potential
P450 2E1 substrates.
PMID- 11013408
TI - Telomere sequences at the novel joints of four independent amplifications in
Saccharomyces cerevisiae.
AB - Primary gene amplification, the mutation from one copy of a gene per genome to
two or more genes per genome is a major mechanism of oncogene overexpression. We
previously developed a system in the yeast Saccharomyces cerevisiae to
phenotypically detect primary amplifications of a reporter cassette, ADH4:CUP1.
We present here the sequence analysis of novel joints from four independent,
spontaneous circular amplifications identified by the ADH4:CUP1 system. All four
novel joints consist of C(1-3) A telomeric repeats joined to short (14- to 16-bp)
CA-rich tracts between ADH4 and the telomere of chromosome VII. In three of the
four amplifications, the telomeric sequence and the CA-rich tract that are joined
in the amplification are normally located in inverted orientation to each other
on chromosome VII. In the fourth amplification, the CA-rich tract on chromosome
VII is joined to telomere sequences from another chromosome. We suggest that
formation of these amplifications was initiated by recombination between these CA
rich tracts and a telomere. The resulting dicentric chromosome could start a
breakage-fusion-bridge cycle that could be resolved by the formation of a
circular amplification structure.
PMID- 11013409
TI - Formation of circular amplifications in Saccharomyces cerevisiae by a breakage
fusion-bridge mechanism.
AB - Primary gene amplification, the mutation from one gene copy per genome to two or
more copies per genome, is a major mechanism of oncogene overexpression in human
cancers. Analysis of the structures of amplifications can provide important
evidence about the mechanism of amplification formation. We report here the
analysis of the structures of four independent spontaneous circular
amplifications of ADH4:CUP1 in the yeast Saccharomyces cerevisiae. The structures
of all four amplifications are consistent with their formation by a breakage
fusion-bridge (BFB) mechanism. All four of these amplifications include a
centromere as predicted by the BFB model. All four of the amplifications have a
novel joint located between the amplified DNA and the telomere, which results in
a dicentric chromosome, and is adjacent to all the copies of the amplified DNA as
predicted by the BFB model. In addition we demonstrated that two of the
amplifications contain most of chromosome VII in an unrearranged form in a 1:1
ratio with the normal copy of chromosome VII, again consistent with the
predictions of the BFB model. Finally, all four amplifications are circular, one
stable endpoint for molecules after breakage- fusion-bridge.
PMID- 11013410
TI - Use of genetically engineered Salmonella typhimurium OY1002/1A2 strain
coexpressing human cytochrome P450 1A2 and NADPH-cytochrome P450 reductase and
bacterial O-acetyltransferase in SOS/umu assay.
AB - The major pathway of bioactivation of procarcinogenic heterocyclic aromatic
amines (HCAs) is cytochrome P450 1A2 (CYP1A2)-catalyzed N-hydroxylation and
subsequent esterification by O-acetyltransferase (O-AT). We have previously
reported that an umu tester strain, Salmonella typhimurium OY1001/1A2,
endogenously coexpressing human CYP1A2 and NADPH-P450 reductase (reductase), is
able to detect the genotoxicity of some aromatic amines [Aryal et al., 1999,
Mutat Res 442:113-120]. To further enhance the sensitivity of the strain toward
HCAs, we developed S. typhimurium OY1002/1A2 by introducing pCW"/1A2:hNPR (a
bicistronic construct coexpressing human P450 1A2 and the reductase) and pOA102
(constructed by subcloning the Salmonella O-AT gene in the pOA101-expressing
umuC"lacZ gene) in S. typhimurium TA1535. In addition, as an O-AT-deficient
strain, we developed the OY1003/1A2 strain by introducing pCW"/1A2:hNPR and
pOA101 into O-AT-deficient S. typhimurium TA1535/1,8-DNP. Strains OY1001/1A2,
OY1002/1A2, and OY1003/1A2 expressed, respectively, about 150, 120, and 140 nmol
CYP1A2/l culture (in whole cells), and respective cytosolic preparations
acetylated 15, 125, and > or = 0 nmol isoniazid/min/mg protein as the O-AT
activities of cytosolic preparations, respectively. We compared the induction of
umuC gene expression as a measure of genotoxicity and observed that the
OY1002/1A2 strain was more sensitive than OY1001/1A2 strain toward the
genotoxicity of 2-amino-1,4-dimethylimidazo[4,5-f]quinol ine(MeIQ), 2-amino-3
methylimidazo[4,5-f]quinoline (IQ),2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline
(MeIQx),2-aminoanthracene, 2-amino-6-methyldipyrido[1,2-a::3,2'-d]i midazole,3
amino-1, 4-dimethyl-5H-pyrido[4,3-b]indole, and 3-amino-1-methyl-5H-pyrido[4, 3
a]indole. However, the genotoxicity of MeIQ, IQ, and MeIQx was not detected with
the OY1003/1A2 strain. These results indicate that the newly developed strain
OY1002/1A2 can be employed in detecting potential genotoxic aromatic amines
requiring bioactivation by CYP1A2 and O-acetyltransferase.
PMID- 11013411
TI - Immunoperoxidase detection of polycyclic aromatic hydrocarbon-DNA adducts in
mouth floor and buccal mucosa cells of smokers and nonsmokers.
AB - Tobacco smoking is a major risk factor for oral cancer; mouth floor and buccal
mucosa are among the most and least cancer-prone subsites, respectively, in the
oral cavity. We investigated the applicability of immunohistochemistry of smoking
induced DNA adducts in oral cells for assessing the exposure to carcinogens, and
estimating the risk for oral cancer. Polycyclic aromatic hydrocarbon (PAH)-DNA
adducts were measured in mouth floor and buccal mucosa cells of smokers (n = 26)
and nonsmokers (n = 22) by means of a semiquantitative immunoperoxidase assay.
Smokers had elevated levels of PAH-DNA adducts compared to nonsmokers in their
mouth floor cells (0.045 +/- 0.022 versus 0.022 +/- 0.016, P = 0.0008 arbitrary
units of immunohistochemistry) as well as in their buccal mucosa cells (0.058 +/-
0.028 versus 0.028 +/- 0.012, P = 0.001). Also, there was a correlation between
the levels of PAH-DNA adducts in mouth floor cells and those in buccal mucosa
cells (r = 0.4, P = 0.01). Furthermore, PAH-DNA adduct levels in both mouth floor
and buccal mucosa cells were significantly related to current smoking indices
(amount of tar and number of cigarettes consumed per day). Expectedly, the levels
of PAH-DNA adducts neither in mouth floor cells nor in buccal mucosa cells, both
being short-lived cells, were related to smoking history index (pack years). The
levels of PAH-DNA adducts, however, in mouth floor cells as the cancer prone
cells were lower than those in buccal mucosa cells (0.037 +/- 0.023 versus 0.044
+/- 0.026, P = 0.04). We conclude that immunohistochemistry of PAH-DNA adducts in
oral cells can be used for exposure assessment of tobacco-related carcinogens,
however, it cannot be used for oral cancer risk estimation.
PMID- 11013413
TI - Adaptation to alkylation damage in DNA measured by the comet assay.
AB - The alkylating mutagens N-methyl-N-nitrosourea (MNU) and methyl methanesulfonate
(MMS) were studied for their potential to induce DNA strand breaks and abasic
(AP) sites in meristematic nuclei of Vicia faba root tips by the comet assay. The
alkaline unwinding/neutral electrophoresis (A/N) and alkaline unwinding/alkaline
electrophoresis (A/A) protocols were used for detection of DNA damage. With the
A/N comet assay, less DNA damage was seen after conditioning pretreatment with a
low dose prior to a high challenging dose of alkylating mutagens as compared to
application of the high dose only, whereas a nearly additive effect was seen when
the A/A comet assay was used. Adaptation was even more obvious when AP sites were
revealed by the AP-endonuclease activity of exonuclease III. The adaptation
observed with the A/N comet assay was abolished by pretreatment with the protein
synthesis inhibitor cycloheximide. These data suggest that the comet assay is
able to detect on molecular level a phenomenon resembling clastogenic adaptation.
PMID- 11013412
TI - Frequency of minisatellite repeat number changes at the MS205 locus in human
sperm before and after cancer chemotherapy.
AB - To determine whether the measurement of repeat number mutations at a
minisatellite locus could detect human germline mutations induced by
chemotherapy, we performed a longitudinal study of the mutation frequencies in
sperm from 10 patients treated for Hodgkin's disease. Polymerase chain reaction
on small pools of DNA equivalent to 100 sperm and Southern blotting were used to
screen at least 7900 sperm in each sample to quantify the mutation frequency at
the minisatellite MS205 locus. Pretreatment and posttreatment semen samples were
obtained at least 2 months after completion of therapy from 4 patients treated
with a regimen (Novantrone, Oncovin, vinblastine and prednisone [NOVP]) that
lacks alkylating agents and from three patients treated with regimens (Cytoxan,
vinblastine, procarbazine and prednisone/Adriamycin, bleomycin, dacarbazine,
lomustine, and prednisone [CVPP/ABDIC] or mechlorethamine, Oncovin, procarbazine
and prednisone [MOPP]) containing alkylating agents. There were no effects of
NOVP or CVPP/ABDIC on the mutation frequencies. In the 1 patient treated with
MOPP, the treatment with the highest dose of gonadotoxic alkylating agents, there
was a statistically significant increase in mutation frequency from 0.79%
pretreatment to 1.14% posttreatment, indicating induction of mutations in stem
spermatogonia. During-treatment semen samples obtained from 2 patients treated
with ABVD, which does not contain gonadotoxic alkylating agents, and 1 with NOVP
also did not show any increases above the baseline mutation frequencies,
indicating no increase in the minisatellite mutation frequency in spermatocytes.
Thus, measurement of repeat number changes at minisatellite MS205 appears to be
able to detect induced germline mutations in human sperm. However, most
chemotherapy regimens do not significantly increase this class of mutations.
PMID- 11013414
TI - Absence of significant genotoxicity in lymphocytes and urine from workers exposed
to moderate levels of cobalt-containing dust: a cross-sectional study.
AB - Mortality studies have shown that, in the past, lung cancer occurred after
exposure to mixtures of cobalt metal and metallic carbide particles, the main
constituents of hard metals, but apparently not when exposure was to cobalt
alone. The major objective of this biomonitoring study was to assess genotoxic
effects as a measure for carcinogenic risk in workers from cobalt refineries and
hard metal plants currently exposed to the threshold limit value/time-weighted
average (TLV-TWA) for cobalt-containing dust. The study comprised three groups of
workers: 35 workers exposed to cobalt dust from three refineries, 29 workers
exposed to hard metal dust from two producing plants, and 35 matched control
subjects recruited from the respective plants. The study design integrated
complementary methodologies to assess biomarkers of effects that represent both
initial DNA damage (8-hydroxydeoxyguanosine [8-OHdG] in urine and comet assay on
lymphocytes) and definitive chromosome breakage/loss (micronuclei in
lymphocytes). Cobalt and cotinine were determined in urine as a measure for
cobalt exposure and recent smoking, respectively. No significant increase of
genotoxic effects was detected in workers exposed to cobalt-containing dust as
compared to controls. No difference in any genotoxicity biomarker was found
between workers exposed to cobalt and hard metal dusts. Multiple regression
analysis indicated that workers who smoked and were exposed to hard metal dusts
had elevated 8-OHdG and micronuclei values. Because this observation is in line
with a previous epidemiological study of an increased risk of dying from lung
cancer in workers from the hard metal industry who smoked, it is concluded that
this specific occupational group needs closer medical surveillance.
PMID- 11013415
TI - Erratum
PMID- 11013416
TI - Analysis of metal complex azo dyes by high-performance liquid
chromatography/electrospray ionization mass spectrometry and multistage mass
spectrometry
AB - Five metal complex azo compounds were analyzed using negative-ion electrospray
ionization mass spectrometry (ESI-MS). Mass spectra of all compounds yield
intense peaks corresponding to [M - H](-) ions without any fragmentation, where M
denotes the neutral compound with a proton as the counterion. Under collision
induced dissociation (CID) conditions, structurally important fragment ions were
studied using the ion trap analyzer with a multistage mass spectrometry (MS(n)
facility. Synthesized compounds with (15)N atoms in the azo group facilitated the
fragmentation pattern recognition. A reversed-phase high-performance liquid
chromatography (HPLC) method using 5 mM ammonium acetate in 70% aqueous
acetonitrile as mobile phase was developed making possible the separation of all
complex compounds tested. The lower detection limits of the ESI-MS method are in
the range 10-20 ng of each compound. The HPLC/ESI-MS method makes possible the
monitoring of ligand exchange in aqueous solutions of metal complex azo dyes, and
also investigation of the stabilities of the complexes in solution. Copyright
2000 John Wiley & Sons, Ltd.
PMID- 11013417
TI - Two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionisation
mass spectrometry of a milk powder.
AB - Proteins in a commercial milk powder have been separated by two-dimensional gel
electrophoresis and analysed by matrix-assisted laser desorption ionisation mass
spectrometry. The mass spectrometric analyses were conducted in two steps:
analysis of the intact proteins following their passive extraction into a
suitable solvent mixture and analysis in reflectron mode of in situ digests of a
number of gel spots. The combination of the two methods allowed a reliable
identification of a number of proteins, including nine caseins as well as certain
protein modifications including single/multiple phosphorylation, lactose-protein
conjugates and Coomassie Brilliant Blue adducts. Analyses of the intact proteins
prior to their in situ digestion contributed to a more efficient and reliable
consultation of protein databases.
PMID- 11013418
TI - Influence of water vapour on selected ion flow tube mass spectrometric analyses
of trace gases in humid air and breath.
AB - Selected ion flow tube mass spectrometry (SIFT-MS) detects and quantifies in real
time the trace gases, M, in air/breath samples introduced directly into a flow
tube. Inevitably, relatively large partial pressures of water vapour are
introduced with the sample and the water molecules become involved in the ion
chemistry on which this analytical technique depends. When H(3)O(+) ions are used
as the precursors for chemical ionisation and SIFT mass spectrometric analyses of
M, they generally result in the formation of MH(+) ions. Also, when water vapour
is present the H(3)O(+) ions are partially converted to hydrated hydronium ions,
H(3)O(+).(H(2)O)(1,2,3). The latter may act as precursor ions and produce new
product ions like MH(+).(H(2)O)(1,2,3) via ligand switching and association
reactions. This ion chemistry and the product ions that result from it must be
accounted for in accurate analyses by SIFT-MS. In this paper we describe the
results of a detailed SIFT study of the reactions involved in the quantification
of acetone, ethyl acetate, diethyl ether, methanol, ethanol, ammonia and methyl
cyanide by SIFT-MS in the presence of water vapour. This study was undertaken to
provide the essential data that allows more accurate analyses of moist air and
breath by SIFT-MS to be achieved. It is shown using our standard analysis
procedure that the error of SIFT-MS quantification caused by the presence of
water vapour is typically 15%. An improved analysis procedure is then presented
that is shown to reduce this error to typically 2%. Additionally, some
fundamental data have been obtained on the association reactions of protonated
organic molecules, MH(+) ions, with water molecules forming MH(+).H(2)O
monohydrate ions. For some types of M, reaction sequences occur that lead to the
formation of dihydrate and trihydrate ions.
PMID- 11013419
TI - Radial stratification of ions as a function of mass to charge ratio in
collisional cooling radio frequency multipoles used as ion guides or ion traps.
AB - Collisional cooling in radio frequency (RF) ion guides has been used in mass
spectrometry as an intermediate step during the transport of ions from high
pressure regions of an ion source into high vacuum regions of a mass analyzer.
Such collisional cooling devices are also increasingly used as 'linear', two
dimensional (2D) ion traps for ion storage and accumulation to achieve improved
sensitivity and dynamic range. We have used the effective potential approach to
study m/z dependent distribution of ions in the devices. Relationships obtained
for the ideal 2D multipole demonstrate that after cooling the ion cloud forms
concentric cylindrical layers, each of them composed of ions having the same m/z
ratio; the higher the m/z, the larger is the radial position occupied by the
ions. This behavior results from the fact that the effective RF focusing is
stronger for ions of lower m/z, pushing these ions closer to the axis. Radial
boundaries of the layers are more distinct for multiply charged ions, compared to
singly charged ions having the same m/z and charge density. In the case of
sufficiently high ion density and low ion kinetic energy, we show that each m/z
layer is separated from its nearest neighbor by a radial gap of low ion density.
The radial gaps of low ion population between the layers are formed due to the
space charge repulsion. Conditions for establishing the m/z stratified structure
include sufficiently high charge density and adequate collisional relaxation.
These conditions are likely to occur in collisional RF multipoles operated as ion
guides or 2D ion traps for external ion accumulation. When linear ion density
increases, the maximum ion cloud radius also increases, and outer layers of high
m/z ions approach the multipole rods and may be ejected. This 'overfilling' of
the multipole capacity results in a strong discrimination against high m/z ions.
A relationship is reported for the maximum linear ion density of a multipole that
is not overfilled.
PMID- 11013420
TI - Characterization of photodegradation products of alachlor in water by on-line
solid-phase extraction liquid chromatography combined with tandem mass
spectrometry and orthogonal-acceleration time-of-flight mass spectrometry.
AB - On-line solid-phase extraction liquid chromatography in combination with mass
spectrometry (MS), i.e. MS/MS and orthogonal-acceleration time-of-flight MS, was
used for the characterization of photodegradation products of alachlor in river
water. Various MS/MS scan functions were used, in particular the precursor-ion
and the daughter-ion modes, to screen for degradation products with structures
closely related to that of alachlor and to obtain information on characteristic
fragments of the degradation products. Elemental compositions of compounds found
and some of their fragments were calculated from the accurate mass information
obtained with orthogonal-acceleration time-of-flight MS. Some ten degradation
products could be characterized by combining various types of mass spectral
information. Since quite a number of isomers were identified, structures of the
degradation products were proposed by considering the most likely fragmentation
patterns in MS/MS experiments. Degradation products of alachlor found in the
current study were compared with those reported in the literature.
PMID- 11013421
TI - Probing protein unfolding through monitoring cysteine alkylation by matrix
assisted laser desorption/ionisation mass spectrometry.
AB - Matrix-assisted laser desorption/ionisation mass spectrometry was used to monitor
interaction between three proteins and two basic Immobiline chemicals (pK 10.3
and pK >12) commonly used in immobilised pH gradients (IPG). For two of the
investigated proteins, the observed alkylation channels of the cysteine residues
exhibited unmistakable response to their gradual denaturation following treatment
with different concentrations (0-8 M) of two commonly used denaturants, urea and
guanidine hydrochloride. Our assessment for protein unfolding is based on the
number and relative intensity of the alkylation channels, yet the present mass
spectrometry data are in good agreement with data based on optical rotatory
dispersion, in which another approach was used to assess protein unfolding.
Whether the present simple, fast and specific mass spectrometry method can be
developed as a probe for monitoring folding/unfolding of cysteine-containing
proteins can only be demonstrated by generating similar data for a larger number
of proteins.
PMID- 11013422
TI - Detection of new propofol metabolites in human urine using gas
chromatography/mass spectrometry and liquid chromatography/mass spectrometry
techniques.
AB - Using hyphenated analytical techniques, gas chromatography/mass spectrometry
(GC/MS) and liquid chromatography/mass spectrometry (LC/MS), a study on minor
propofol metabolites in human urine was conducted. These techniques allowed
identification of two new phase I metabolites (2-(omega-propanol)-6
isopropylphenol and 2-(omega-propanol)-6-isopropyl-1,4-quinol). In addition,
their four corresponding conjugates (three glucuronides and one sulphate) were
detected. Thus in human urine at least eight conjugate metabolites are produced,
derived from four different aglycones (propofol; 2, 6-diisopropyl-1,4-quinol; 2
(omega-propanol)-6-isopropylphenol and 2-(omega-propanol)-6-isopropyl-1,4
quinol).
PMID- 11013423
TI - Fast, generic gradient high performance liquid chromatography coupled to fourier
transform ion cyclotron resonance mass spectrometry for the accurate mass
analysis of mixtures
AB - Fast gradient high performance liquid chromatography (HPLC) has been combined
with a commercially available Fourier transform ion cyclotron resonance (FTICR)
mass spectrometer for the routine and high performance analysis of mixtures. With
this combination we were able to separate and detect, under high mass accuracy
conditions, a six-component drug mixture in less than 5 minutes. The fast
gradients described are now possible due to the development of mechanically
robust, ultra pure silica packing materials, which allow relatively high flow
rates (ca. 1 mL/min for a 2 mm diameter column). For the six compounds present in
the model mixture, relative mass errors of less than 1 ppm were obtained (based
on an external calibration) providing sufficient mass accuracy to make
unequivocal assignments of empirical formulae. Preliminary results of fast
gradient HPLC/FTICR-MS/MS are also shown for the same six-component mixture.
Copyright 2000 John Wiley & Sons, Ltd.
PMID- 11013424
TI - High-throughput cytochrome P450 inhibition screening via cassette probe-dosing
strategy. IV. Validation of a direct injection on-line guard cartridge
extraction/tandem mass spectrometry method for simultaneous CYP3A4, 2D6 and 2E1
inhibition assessment.
AB - A highly efficient direct injection on-line guard cartridge extraction/tandem
mass spectrometry (DI-GCE/MS/MS) method has been validated for high-throughput
evaluation of cytochrome P450 (CYP) 3A4, 2D6 and 2E1 inhibition potential via
cassette dosing of midazolam, dextromethorphan and chlorzoxazone using human
hepatic microsomes and 96-well microtiter plates. Microsomal incubations were
terminated with formic acid, centrifuged, and the resulting supernatants were
injected for analysis by DI-GCE/MS/MS. Due to the novel use of an extremely short
C(18) guard cartridge (4 mm in length), this method exhibits several advantages
such as no sample preparation, excellent on-line extraction, short run time (2.5
min), and minimized source contamination and performance deterioration. The DI
GCE/MS/MS method demonstrates acceptable accuracy and precision for the
simultaneous quantification of 1'-hydroxymidazolam, dextrorphan and 6
hydroxychlorzoxazone in microsomal incubations. The inhibition potential of
CYP3A4, 2D6 and 2E1 has been evaluated using their known selective inhibitors.
The IC(50) values measured by the cassette dosing approach (high-throughput) are
consistent with those observed by an individual dosing regimen (conventional) and
are all in good agreement with the literature values. The results suggest that
the cassette probe-dosing strategy may provide an in vitro approach to minimize
cost while maximizing throughput of CYP inhibition evaluation of new chemical
entities in support of drug discovery and development.
PMID- 11013425
TI - Fragmentation of 3,7-dialkyl-1,5-diphenyl-3,7-diazabicyclo[3.3. 1]nonan-9-ones
under electron ionization.
AB - A series of 3,7-dialkyl-1,5-diphenyl-3,7-diazabicyclo[3.3. 1]nonan-9-ones was
prepared, and the details of their fragmentation under electron ionization (EI)
were elucidated. The molecular ions of each compound under consideration were
quite abundant in their EI spectra. Full-scan spectra exhibited a number of
fragment ions which were clearly assigned using MS/MS and accurate mass
measurements. The basic fragmentation of 3,7-dialkyl-1,5-diphenylbispidinones was
due to the cleavage of C(1)-C(2) bond followed by a hydrogen migration similar to
an odd-electron McLafferty rearrangement. Alternatively, the C(1)-C(2) bond
cleavage was followed by the elimination of an imine molecule, Alk-N=CH(2).
Further fragmentation resulted in ions at m/z 234 and 103, present in the spectra
of all the compounds under study. The fragmentation pathways proposed in this
paper are based on the substituent shifts, accurate mass measurements and
collision-induced dissociation spectra of selected ions. The results of the
present work can be useful in selecting the fragment ions suitable for
identification and quantitation of bispidinones in biological matrices.
PMID- 11013426
TI - Tandem mass spectrometry in the determination of 4-hydroxy-2-nonenal at the
cellular level.
PMID- 11013427
TI - Nuclear transfer and cell transplantation: making more with less.
AB - Pig cloning can be achieved by transfer of nuclei of differentiated somatic cells
into enucleated oocytes. Then, developing embryos are placed into surrogate
mothers for further development to full term. Although cloned pigs offer the
possibility of unlimited organ supply for compatible xenotransplantation in
humans, the yield of a predictable number of offspring is still at an
experimental phase. Spermatogonial stem cells from a fertile donor can be
transplanted to the testes of infertile recipients and generate sperm. At
present, results from xenogeneic spermatogenesis by transplantation indicate that
porcine, bovine and equine spermatogonia find the interior of the seminiferous
tubular environment not favorable for further differentiation into meiotic
prophase spermatocytes. Spermatogenic cell transplantation is a promising
experimental alternative for understanding the conditions required by both the
donor cells and the recipient testis to coexist and even cooperate towards the
full development of fertilizing sperm.
PMID- 11013428
TI - Paternal exposure to cyclophosphamide dysregulates the gene activation program in
rat preimplantation embryos.
AB - Although there has been progress in determining the mechanisms by which maternal
toxicant exposure affects progeny, there is little information on the actions of
drugs administered to the father. We investigated the effects of pre-conceptional
paternal exposure to cyclophosphamide, an anti-cancer agent, on embryonic gene
activation in the rat. The male pronucleus was formed earlier in embryos sired by
cyclophosphamide-treated male rats than in those sired by controls; early male
pronucleus formation was followed by alterations in the gene activation program.
BrUTP incorporation into RNA and Sp1 transcription factor immunostaining were
increased and spread over both cytoplasmic and nuclear compartments in 2-cell
embryos sired by cyclophosphamide-treated males compared to controls. Total RNA
synthesis was constant in 1-8 cell embryos sired by drug-treated fathers, while
in control embryos RNA synthesis increased four-fold to peak at the 4-cell stage.
In 2-cell embryos sired by drug-treated males, the relative abundance of
candidate imprinted genes was elevated significantly above control; a peak in the
expression of these genes was not observed until the 8-cell stage in control
embryos. Thus, paternal drug exposure temporally and spatially dysregulated rat
zygotic gene activation, altering the developmental clock.
PMID- 11013429
TI - Detection of PACH1, a nuclear factor implicated in the transcriptional regulation
of meiotic and early haploid stages of spermatogenesis.
AB - Spermatogenesis occurs in a series of well-defined stages and serves as an
excellent model for lineage-specific cell development. Yet, little is known
regarding the transcriptional mechanisms responsible for cell- and stage
dependent gene regulation in the male germ line. The rat and mouse proenkephalin
genes are expressed from an alternative, spermatogenic cell-specific promoter
specifically in meiotically-active pachytene spermatocytes and early post-meiotic
spermatids. This promoter thus serves as an excellent model for defining
transcriptional regulators involved in germ line-specific gene expression in
meiotic cells. Previous transgenic studies identified a proximal, 51 bp 5'
flanking sequence containing two direct repeat elements that are absolutely
required for in vivo proenkephalin promoter activity in spermatocytes and
spermatids. Here, footprinting analyses were used to further delineate the
specific interactions of a spermatogenic cell nuclear factor with the repeat
elements within the proximal promoter region. This repeat-binding factor was also
shown to be developmentally upregulated specifically in pachytene spermatocytes.
Using Southwestern analysis, we have identified a unique nuclear protein enriched
in pachytene spermatocytes that specifically recognizes the repeat elements
within the proximal 5'-flanking sequence. We propose that this DNA binding
factor, termed PACH1, is a key transcriptional regulator of the proenkephalin and
potentially other gene promoters, uniquely expressed during meiosis in the male
germ line.
PMID- 11013431
TI - Organization of a gene coding for an oviduct-specific glycoprotein (oviductin) in
the hamster.
AB - Hamster oviductin, a high molecular weight glycoprotein secreted by the oviducts,
is believed to participate in fertilization and protection of the tubal
epithelium. Expression of the oviductin gene is confined strictly to nonciliated
secretory cells of the oviduct and is regulated by hormones. The objective of
this study was to characterize the genomic organization and to identify potential
regulatory elements implicated in the control of transcription of the oviductin
gene. Polymerase chain reaction was performed on hamster genomic DNA, yielding
2.2 kb of the 5' flanking region as well as 13.6 kb of genomic sequence
comprising the entire coding sequence of the oviductin gene distributed in 11
exons. Sequencing of the 5' flanking region revealed, among other elements, an
almost perfect estrogen-responsive element (GGTCACTGTGACT), an atypical TATA box
(TATTAA), and a perfect inverted Sp1 site located between the transcription start
site and the atypical TATA box. Primer extension analyses indicated that the
hamster oviductin transcript possesses an unusually short 5' untranslated region
of only 14 nucleotides. The distinct organization of the hamster oviductin gene
in the vicinity of the transcription start site provides an interesting ground
for further functional studies.
PMID- 11013430
TI - Evaluation of heterologous insulator function with regard to chromosomal position
effect in the mouse blastocyst and fetus.
AB - Insulators are located at the boundaries of differentially regulated genes and
delimit their interactions by establishing independent chromatin structures.
Recently, an insulator sequence has been found in the 5'-flanking region of
arylsulfatase (ARS) gene from sea urchin. To investigate functional conservation
of this ARS insulator in mice, we performed blastocyst assays to evaluate the
effect of this insulator on the chromosomal position effect, quantitatively. We
constructed transgenes that have a luciferase gene under the control of the CMV
IE enhancer and the human elongation factor 1 alpha promoter in the presence or
absence of the ARS insulator in both flanking regions. These transgenes were
microinjected into 1-cell mouse embryos and luciferase activity was measured at
the blastocyst stage. We found that the presence of ARS insulator sequence
doubled the number of luciferase-expressing blastocysts, and that the proportion
of the blastocysts with high-level expression (> or = 1 x 10(4) relative light
units (RLU)) was increased more than tenfold. In the case of transgenic fetuses,
however, the presence of ARS insulator did not seem to improve transgene
expression. These results suggest that the sea urchin ARS insulator confers
position-independent expression driven by the human elongation factor 1 alpha
promoter, at least in the blastocyst stage of the mouse.
PMID- 11013432
TI - Preimplantation bovine embryos express mRNA of growth hormone receptor and
respond to growth hormone addition during in vitro development.
AB - In previous studies we demonstrated that bovine cumulus oocyte complexes (COCs)
obtained from small and medium sized follicles express growth hormone receptor
(GHR) mRNA and respond to growth hormone (GH) addition during in vitro
maturation. The aim of this study was to investigate whether bovine zygotes and
preimplantation embryos continue the expression of GHR gene after in vitro
fertilization and during early embryo development and whether supplementation of
GH during embryo culture affects embryo development. Therefore, COCs obtained
from small and medium sized follicles were cultured in M199 supplemented with 10%
FCS and gonadotropins for 24 hr. After in vitro fertilization the embryos were
cultured: (a) on a monolayer of buffalo rat liver (BRL) cells in M199
supplemented with 10% FCS and 100 ng/ml bovine GH (NIH-GH-B18); (b) in droplets
of serum-free BRL-conditioned medium supplemented with 100 ng/ml GH; (c) in
droplets of synthetic oviductal fluid (SOF) supplemented with 100 ng/ml GH.
Cultures without GH served as controls. Embryos were scored morphologically and
the efficiency of the culture system was evaluated (a) as the percentage of
cleaved embryos 4 days after IVF, (b) the percentage of blastocysts on Day 9
expressed on the basis of the number of oocytes at the onset of culture, and (c)
the percentage of hatched blastocysts on Day 11 expressed on the basis of the
total number of blastocysts present at Day 9. For gene expression, immature (GV)
and mature (MII) oocytes (as positive control), embryos with less than 8 cells,
16-32 cells, and hatched blastocysts were prepared for reverse transcriptase
polymerase chain reaction (RT-PCR) to assess the expression of mRNA of GHR.
Messenger RNA for GHR was found in GV and MII oocytes and in all stages of embryo
development. No mRNA for GH could be detected in early and expanded blastocysts
produced in SOF medium. Immunoreactive GHR was found both in trophoblastic and
embryonic cells of hatched blastocysts. Addition of 100 ng/ml GH during embryo
culture on a monolayer of BRL cells in M199 supplemented with 10% FCS did not
affect embryo development. However, GH (100 ng/ml) supplementation during embryo
culture in droplets of serum-free BRL conditioned medium significantly (P < 0.05)
enhanced the proportion of > 8-cell embryos. Similarly, culture of embryos in
droplets of SOF medium in the presence of GH (100 ng/ml) significantly (P < 0.05)
enhanced the number of > 8-cell embryos from 53.8% in control to 70.6% in GH
treated group. Day 9 blastocyst formation in SOF medium was also significantly (P
< 0.01) increased in the presence of GH (33.9%) compared to the control (20.2%).
Embryos cultured in SOF without GH rarely resulted in hatched blastocysts (0.7%).
However, GH supplementation remarkably enhanced the proportion of the hatched
blastocysts (13%). In conclusion, expression of GHR gene in preimplantation
bovine embryos, presence of the receptor, and the beneficial effect of GH on
cleavage, blastocyst formation and hatchability of the embryos point to the
involvement of GH in early embryonic development.
PMID- 11013433
TI - EDTA stimulates cleavage stage bovine embryo development in culture but inhibits
blastocyst development and differentiation.
AB - Culture of bovine zygotes in medium SOFaa supplemented with 100 microM EDTA
significantly increased cleavage rates during the first 72 hr of development
compared to development in SOFaa. However, continued culture in the presence of
EDTA for a further 72 hr (total of 6 days of culture) resulted in significantly
reduced development to the morulae/blastocyst and blastocyst stages compared to
culture without EDTA. Highest rates of development to the morulae/blastocyst
stage (56.5%) and to the blastocyst stage (43.2%) were achieved when zygotes were
cultured for 72 hr with EDTA before transfer to medium SOFaa without EDTA.
Resultant blastocysts also had significantly increased blastocyst cell number and
ICM cell number compared to those cultured without EDTA in the first 72 hr. EDTA
was shown to inhibit glycolytic activity of the cleavage stage embryo, thereby
preventing the premature stimulation of glycolysis and enhancing development.
However, EDTA should not be used for the later stage embryo as the inhibition of
glycolysis reduces energy production at the blastocyst stage and significantly
inhibits inner cell mass development.
PMID- 11013434
TI - In vitro development of porcine nuclear transfer embryos constructed using fetal
fibroblasts.
AB - The in vitro development of porcine nuclear transfer embryos constructed using
primary cultures from day 25 fetal fibroblasts which were either rapidly dividing
(cycling) or had their cell-cycle synchronized in G0/G1 using serum starvation
(serum-starved) was examined. Oocyte-karyoplast complexes were fused and
activated simultaneously and then cultured in vitro for seven days to assess
development. Fusion rates were not different for either cell population. The
proportion of reconstructed embryos that cleaved was higher in the cycling group
compared to the serum-starved group (79 vs. 56% respectively; P < 0.05).
Development to the 4-cell stage was not different using either population. Both
treatments supported similar rates of development to the morula (1.5 vs. 7%,
cycling vs. serum-starved) and blastocyst stage (1.5 vs. 3%, cycling vs. serum
starved). The blastocyst produced using cycling cells had a total cell number of
10. Total cell numbers for the three blastocysts produced serum-starved cells
were 22, 24, and 33. These blastocysts had inner cell mass numbers of 0, 15, and
4, respectively. Six hundred and thirty-five nuclear transfer embryos
reconstructed using serum-starved cells were transferred to 15 temporarily mated
recipients for 3-4 days. Of these, 486 were recovered (77% recovery rate) of
which 106 (22%) had developed to the 4-cell stage or later. These were
transferred to a total of 15 recipients which were either unmated or mated. Seven
recipients farrowed a total of 51 piglets. Microsatellite analysis revealed that
none of these were derived from the nuclear transfer embryos transferred.
PMID- 11013435
TI - Germ cell transplantation from large domestic animals into mouse testes.
AB - Donor-derived spermatogenesis after spermatogonial transplantation to recipient
animals could serve as a novel approach to manipulate the male germ line in
species where current methods of genetic modification are still inefficient. The
objective of the present study was to investigate germ cell transplantation from
boars, bulls, and stallions, which are economically important domestic animals,
to mouse recipients. Donor testis cells (fresh, cryopreserved, or cultured for 1
month) were transplanted into testes of immunodeficient recipient mice in which
endogenous spermatogenesis had been destroyed. Recipient testes were analyzed
from 1 to > 12 months after transplantation for the presence of donor germ cells
by donor-specific immunohistochemistry. Donor cells were present in most
recipient testes with species-dependent differences in pattern and extent of
colonization. Porcine donor germ cells formed chains and networks of round cells
connected by intercellular bridges but later stages of donor-derived
spermatogenesis were not observed. Transplanted bovine testis cells initially
appeared similar but then developed predominantly into fibrous tissue within
recipient seminiferous tubules. Few equine germ cells proliferated in mouse
testes with no obvious difference between cells recovered from a scrotal or a
cryptorchid donor testis. The pattern of colonization after transplantation of
cultured cells did not resemble spermatogonial proliferation. These results
indicate that fresh or cryopreserved germ cells from large animals can colonize
the mouse testis but do not differentiate beyond the stage of spermatogonial
expansion. Species-specific differences in the compatibility of large animal
donors and mouse recipients were detected which cannot be predicted solely on the
basis of phylogenetic distance between donor and recipient species.
PMID- 11013436
TI - Maturational changes of the CD52-like epididymal glycoprotein on cynomolgus
monkey sperm and their apparent reversal in capacitation conditions.
AB - A major epididymal secretory protein in men has a colinear cDNA sequence with
lymphocyte CD52, a sialylated glycoprotein. Immunostaining and flow cytometric
detection of cynomolgus monkey sperm CD52 during epididymal maturation showed
increases from 20 to 85% stained sperm from the caput to the corpus with staining
intensities doubled. Freshly prepared cauda sperm showed only 10% staining while
they markedly increased in percentage and intensity of staining upon incubation
at 37 degrees C under capacitating conditions, but not at 4 degrees C. Western
blotting of proteins from fresh cauda sperm revealed no less antigen than corpus
sperm. Staining of ejaculated sperm exhibited similar increases during
incubation. Further washing with a high salt medium before staining to remove any
electrostatically-bound molecules masking the antigen showed no effect.
Incubation-induced increases in antigen binding were accelerated by the addition
of neuraminidase (0.25 and 0.5 U/ml), but not affected by the sialyl residue-rich
fetuin (5 mg/ml) competing for any endogenous neuraminidase. There were no
concomitant decreases in the staining of sialic acid residues during capacitation
incubation. These findings suggest a cryptic antigen epitope site as a
consequence of sperm maturation and subsequent re-exposure under capacitation
conditions, but not due to the removal of sialic acid residues by endogenous
neuraminidase. Involvement of endogenous proteases was also ruled out, as
incubation in the presence of protease inhibitors did not hinder the increases
but resulted in a dose-dependent enhancement in staining, suggesting some
protease-sensitive unmasking process. In conclusion, the monkey epididymal
secreted CD52 on sperm underwent changes in antigenic characteristics during
sperm maturation which were reversed under capacitation conditions.
PMID- 11013437
TI - Porcine oocyte activation induced by a cytosolic sperm factor.
AB - It is not known how the fertilizing sperm elicits the release of Ca(2+) from the
oocyte's intracellular stores. We investigated whether a crude extract isolated
from boar sperm could induce the Ca(2+) release and trigger subsequent early and
late activation events upon injection into matured porcine oocytes. The sperm
extract induced an immediate rise in the intracellular free Ca(2+) concentration
in all oocytes tested, which was followed by repetitive Ca(2+) transients in 11
out of 14 oocytes. Heat or trypsin treatment of the extract totally abolished the
Ca(2+) releasing activity of the sperm factor. The injected oocytes showed
cortical granule exocytosis, they resumed meiosis and entered first interphase:
pronuclei were formed in 89.2% (132/148) of the cases. Pronuclear formation was
accompanied by the appearance of a new 22 kDa protein as normally seen at
fertilization. Of the successfully injected oocytes 51.7% (105/203) cleaved and
2.0% (4/203) developed to the blastocyst stage after being cultured for 7 days in
NCSU 23 medium. Injection of the carrier medium could not trigger these changes.
The results indicate that the sperm might activate porcine oocytes by introducing
a soluble factor into the oocyte's cytoplasm after gamete fusion.
PMID- 11013438
TI - Differential expression of glycoside residues in the mammalian zona pellucida.
AB - The mammalian zona pellucida is an extracellular matrix surrounding the oocyte,
and is composed of three major glycoproteins, ZP1, ZP2, and ZP3. Previous studies
have suggested that the sperm receptor activity of the zona pellucida resides in
specific oligosaccharide chains on the ZP3 glycoprotein. However, the nature of
the terminal monosaccharide(s) on these glycosidic chains to which sperm bind is
a matter of active debate. Evidence has been presented to support a role for at
least three distinct monosaccharides in sperm binding, alpha-galactose, L-fucose
on Lewis X structures, and beta-N-acetylglucosamine. Previous studies have shown
that beta-N-acetylglucosamine is uniformly distributed throughout the zona
matrix. In this study, we have investigated the expression and distribution of
alpha-galactose and fucose moieties during the maturation of the zona pellucida
in mouse, rat, and hamster. Interestingly, alpha-galactose residues are expressed
only during later stages of zona secretion and, consequently, are confined to the
inner portions of the mature zona pellucida in mouse and rat. In hamster, alpha
galactose residues are only detectable in the zona pellucida of ovulated eggs,
and are not found in ovarian oocytes. Fucosyl residues linked to Lewis X
glycosides are not detectable at any stage of zona maturation in these three
species, whereas fucose linked to N-linked core oligosaccharides are present
throughout the zona. These studies indicate a previously unappreciated
heterogeneity in the composition of zona glycosides. The specific localization of
alpha-galactose residues to the inner portions of the zona matrix suggest a role
in the later stages of sperm penetration through the zona. Finally, due to their
absence from the zona surface, alpha-galactose and Lewis X fucosyl residues are
not likely to be mediators of primary sperm binding.
PMID- 11013439
TI - Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric
hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant
hypocalcemia.
AB - The calcium-sensing receptor (CASR) is a plasma membrane G protein coupled
receptor that is expressed in the parathyroid hormone (PTH) producing chief cells
of the parathyroid gland and the cells lining the kidney tubule. By virtue of its
ability to sense small changes in circulating calcium concentration ([Ca(2+)](o))
and to couple this information to intracellular signaling pathways that modify
PTH secretion or renal cation handling, the CASR plays an essential role in
maintaining mineral ion homeostasis. Inherited abnormalities of the CASR gene
located on chromosome 3p13.3-21 can cause either hypercalcemia or hypocalcemia
depending upon whether they are inactivating or activating, respectively.
Heterozygous loss-of-function mutations give rise to familial (benign)
hypocalciuric hypercalcemia (FHH) in which the lifelong hypercalcemia is
asymptomatic. The homozygous condition manifests itself as neonatal severe
hyperparathyroidism (NSHPT), a rare disorder characterized by extreme
hypercalcemia and the bony changes of hyperparathyroidism which occur in infancy.
The disorder autosomal dominant hypocalcemia (ADH) is due to gain-of-function
mutations in the CASR gene. ADH may be asymptomatic or present with neonatal or
childhood seizures. A common polymorphism in the intracellular tail of the CASR,
Ala to Ser at position 986, has a modest effect on the serum calcium
concentration in healthy individuals.
PMID- 11013440
TI - Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase
(UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to
phenotype.
AB - Uridine-diphosphoglucuronate glucuronosyltransferases (UGTs) are a family of
enzymes that conjugate various endogenous and exogenous compounds with glucuronic
acid and facilitate their excretion in the bile. Bilirubin-UGT(1) (UGT1A1) is the
only isoform that significantly contributes to the conjugation of bilirubin.
Lesions in the gene encoding bilirubin-UGT(1), lead to complete or partial
inactivation of the enzyme causing the rare autosomal recessively inherited
conditions, Crigler-Najjar syndrome type-1 (CN-1) and type 2 (CN-2),
respectively. Inactivation of the enzyme leads to accumulation of unconjugated
bilirubin in the serum. Severe hyperbilirubinemia seen in CN-1 can cause
bilirubin encephalopathy (kernicterus). Kernicterus can be fatal or may leave
behind permanent neurological sequelae. Here, we have compiled more than 50
genetic lesions of UGT1A1 that cause CN-1 (including 9 novel mutations) or CN-2
(including 3 novel mutations) and have presented a correlation of structure to
function of UGT1A1. In contrast to Crigler-Najjar syndromes, Gilbert syndrome is
a common inherited condition characterized by mild hyperbilirubinemia. An
insertional mutation of the TATAA element upstream to UGT1A1 results in a reduced
level of expression of the gene. Homozygosity for the variant promoter is
required for Gilbert syndrome, but not sufficient for manifestation of
hyperbilirubinemia, which is partly dependent on the rate of bilirubin
production. Several structural mutations of UGT1A1, for example, a G71R
substitution, have been reported to cause mild reduction of UGT activity toward
bilirubin, resulting in mild hyperbilirubinemia, consistent with Gilbert
syndrome. When the normal allele of a heterozygote carrier for a Crigler-Najjar
type structural mutation contains a Gilbert type promoter, intermediate levels of
hyperbilirubinemia, consistent with the diagnosis of CN-2, may be observed.
PMID- 11013441
TI - Characterization of two unusual RS1 gene deletions segregating in Danish
retinoschisis families.
AB - Over 100 distinct retinoschisis gene (RS1) mutations, of which approximately 10%
are single exon deletions, have been described to date. In this paper we have
characterized in detail two dissimilar RS1 gene deletions which are accountable
for RS in one-third of Danish patients. First, a 136 kb deletion, spanning from
the 5' region of the RS1 gene to intron 3, was identified. Unexpectedly this
large deletion abolishes exons of three adjacent genes: serine-threonine
phosphatase gene (PPEF-1)/serine-threonine protein phosphatase gene (PP7),
retinoschisis gene (RS1), and serine-threonine kinase gene (STK9). We demonstrate
that the RS1 and STK9 genes are partly overlapping and the sequences of the PP7
and PPEF-1 genes are identical. This is the first study which reports of
retinoschisis patients who also suffer from deletions in genes adjacent to RS1.
The 136 kb deletion is also the first gross deletion of the retinoschisis gene
deleting three exons. It results from a recombination between two repetitive
sequences of the Alu family, one in 5' region of the RS1 gene and the other in
RS1 intron 3. The second alteration, the actual Danish RS founder mutation, is a
4.4 kb noncontiguous two-part deletion composed of two deleted 1.5 and 2.9 kb
segments, separated by an intact 1.2 kb segment. It extends from the 5' flanking
region of the retinoschisis gene to RS intron 1. RS1 gene deletions of this type
have not been identified previously. Despite these two unique deletions, which
either lead to severely defective transcription or total absence of the
retinoschisin and PPEF-1 protein, all the patients have a typical retinoschisis
phenotype.
PMID- 11013442
TI - High mutation detection rate in TCOF1 among Treacher Collins syndrome patients
reveals clustering of mutations and 16 novel pathogenic changes.
AB - Twenty-eight families with a clinical diagnosis of Treacher Collins syndrome were
screened for mutations in the 25 coding exons of TCOF1 and their adjacent splice
junctions through SSCP and direct sequencing. Pathogenic mutations were detected
in 26 patients, yielding the highest detection rate reported so far for this
disease (93%) and bringing the number of known disease-causing mutations from 35
to 51. This is the first report to describe clustering of pathogenic mutations.
Thirteen novel polymorphic alterations were characterized, confirming previous
reports that TCOF1 has an unusually high rate of single-nucleotide polymorphisms
(SNPs) within its coding region. We suggest a possible different mechanism
leading to TCS or genetic heterogeneity for this condition, as we identified two
families with no apparent pathogenic mutation in the gene. Furthermore, our data
confirm the absence of genotype-phenotype correlation and reinforce that the
apparent anticipation often observed in TCS families is due to ascertainment
bias.
PMID- 11013443
TI - Diverse deletions in the growth hormone receptor gene cause growth hormone
insensitivity syndrome.
AB - Growth hormone insensitivity syndrome (GHIS; also known as Laron syndrome), is
characterized by severe postnatal growth failure and normal growth hormone. The
syndrome is frequently caused by point mutations in the growth hormone receptor
gene (GHR). Here we report five families with GHIS and partial deletions of the
GHR gene. The deletion breakpoints were sequenced and PCR-based diagnostic tests
were developed. In a Cambodian family, a novel deletion removed part of exon 5
and 1.2 kb of the preceding intron. The deletion occurred by recombination within
four identical nucleotides. In the mutant transcript, skipping of the truncated
exon 5 leads to a frameshift and premature termination codon (PTC). A previously
reported discontinuous deletion of GHR exons 3, 5, and 6 was identified in three
Oriental Jewish families. An unaffected individual was heterozygous for the exon
5 and 6 deletion, but homozygously deleted for exon 3 suggesting that the exon 3
deletion is a polymorphism. The pathogenic deletion of exons 5 and 6 spans about
7.5 kb. Sequence analysis of the breakpoints revealed an imperfect junction
between introns 4 and 6, with a four basepair insertion. A novel deletion of 13
nucleotides within exon 9 was identified in a Caucasian girl with GHIS who
carries the I153T missense mutation on her other allele. The exon 9 deletion
leads to a frameshift and PTC. The predicted protein retains the transmembrane
domain and a short cytoplasmic tail. Four family members in three generations
were carriers of this deletion, but only two of them were below normal for
height, suggesting that this mutation by itself does not act as a dominant
negative, as was reported for two other GHR mutations which lead to truncation of
the intracellular domain.
PMID- 11013444
TI - Direct genomic multiplex PCR for BRCA1 and application to mutation detection by
single-strand conformation and heteroduplex analysis.
AB - Most mutation detection methods are based on analysis of PCR amplified segments
and the application of multiplex PCR is one central approach to improving
screening efficiency. Genes like the breast-ovarian cancer susceptibility gene
BRCA1 pose a difficult challenge to efficient mutation screening because of large
coding regions, numerous exons, and complex mutational spectra. The application
to BRCA1 of a general approach to effective multiplex PCR is described here.
Fifteen triplex PCRs and a single PCR reaction condition were used for
amplification of all BRCA1 coding regions and the BRCA1-specific segments from
the duplicated promoter region. SSCP/HDX gel analysis of the multiplex products
detected mobility distinctions for 34/34 sets of allelic BRCA1 fragments. A novel
polymorphism was found, CTTCT(4)CT(10)CT(12) >CT(4)CT(11), a compound deletion in
a region beginning at the +33 position of IVS7 and resulting in a net deletion of
15 bp. This change was shown to be one of the common polymorphisms that define
the two major haplotypes of the BRCA1-RNU2 region in a large proportion of the
world population. A triplex PCR for SSCP detection of this deletion and two other
distantly located common polymorphisms may be used to screen haplotype content
and facilitate comparison of samples with similar haplotypes in subsequent
mutation screening. The approach for robust multiplex amplification is generally
applicable and allows rapid development of efficient testing for a wide variety
of mutations in any gene(s) encompassing a large coding region or numerous exons
and including as many as 50 different genomic PCR products.
PMID- 11013445
TI - Identification of specific BRCA1 and BRCA2 variants by DHPLC.
AB - Denaturing high performance liquid chromatography (DHPLC) is generating
increasing interest in clinical genetics as a reliable tool for the analysis of
genetic alterations. In the work presented here our intentions were to optimize
primer design and DHPLC analysis conditions for a qualitative detection of BRCA1
and BRCA2 variations. The BRCA1 and BRAC2 genes display a high proportion of
polymorphisms. Sequencing efforts geared towards the distinction of tumor-related
mutations and benign variants still remain time-consuming and expensive. DHPLC
elution profiles, however, permit the correlation of a characteristic
chromatographic profile with a specific sequence alteration. In this study we
evaluate the sensitivity of DHPLC for the identification of unique polymorphisms,
which are frequent in the Caucasian population, in lieu of sequence analysis. The
complete BRCA1 gene and parts of BRCA2 were examined. In the case of BRCA1, 431
out of 432 heterozygotes were identified correctly. In addition, 18 new profiles
were identified which had not been detected previously in our studies and which
represented new mutations or rare polymorphisms. For BRCA2, 135 out of 137 simple
sequence variants were classified correctly. In addition, six new profiles were
identified which represented new mutations or rare polymorphisms.
PMID- 11013446
TI - Oligonucleotide microarray based detection of repetitive sequence changes.
AB - Prior studies of oligonucleotide microarray-based mutational analysis have
demonstrated excellent sensitivity and specificity except in circumstances where
a frameshift mutation occurs in the context of a short repeated sequence. To
further evaluate this circumstance, a series of nucleic acid samples having
heterozygous mutations within repetitive BRCA1 sequence tracts was prepared and
evaluated. These mutations included single nucleotide insertions and deletions in
homopolymer runs, insertions and deletions of trinucleotide repeats, and
duplications. Two-color comparative hybridization experiments were used wherein
wild type reference and test targets are co-hybridized to microarrays designed to
screen the entire BRCA1 coding sequence for all possible sequence changes.
Mutations in simulated heterozygote samples were detected by observing relative
losses of test target hybridization signal to select perfect match
oligonucleotide probes. While heterozygous mutations could be readily
distinguished above background noise in 9/19 cases, it was not possible to detect
alterations in a poly dA/dT tract, small triplet repeat expansions, and a 10 bp
direct repeat. Unexpectedly, samples containing (GAT)(3) triplet repeat
expansions showed significantly higher affinity toward specific perfect match
probes relative to their wild type counterparts. Therefore, markedly increased as
well as decreased test sample hybridization to perfect match probes should be
used to raise a suspicion of repetitive sequence changes.
PMID- 11013447
TI - DNA 2000: International Symposium on the State-of-the-Art in Genetic Analysis,
June 1-3, 2000, Boston, U.S.A.
AB - DNA 2000, an international symposium on state-of-the-art genetic analysis, was
held at the Back Bay Hilton in Boston, Massachusetts, on 1-3 June, 2000. Meeting
highlights are described. The meeting was organized and sponsored by the
California Separation Science Society (CaSSS; www.casss.org) and other co
sponsors including the Human Genome Organisation (HUGO). DNA 2000 brought
together a group of specialists in DNA detection and analysis methods from around
the world in a venue presenting not only new technologies but also their
applications in candidate gene studies, molecular diagnosis, analysis of complex
diseases, and even studying the origin and evolution of humans.
PMID- 11013448
TI - Allelic imbalance of BRCA1 transcript in the IVS20 12-bp insertion carrier.
AB - One of the unclassified variants of the BRCA1 gene which has drawn considerable
attention in recent years is the 12-bp insertion/duplication in intron 20. In
this report, we show that a contribution from one chromosome cannot be detected
in the BRCA1 transcript of the 12 bp insertion carrier. We also demonstrate here
that the single transcript variant we observe by cDNA analysis originates from
the same BRCA1 allele that harbours the 12-bp insertion. Hum Mutat 16:371, 2000.
PMID- 11013449
TI - Factor IX mutations in South Africans and African Americans are compatible with
primarily endogenous influences upon recent germline mutations.
AB - Similar patterns of germline mutations in the factor IX gene (F9) have been
observed in certain geographically and racially diverse populations. Germline
mutation data have not been available from any region of Africa or from the Black
race. Analysis of mutation data for Blacks is of interest, since this race has a
high frequency of polymorphism compared to other races. This high frequency has
been interpreted as evidence for the "out of Africa" hypothesis for the origin of
humans, but it is possible that Blacks have a higher mutation rate due to genetic
differences or environmental exposures. We report 26 independent mutations that
were detected in patients of mixed races with hemophilia B from South Africa. The
pattern of mutation in patients from this African country was similar to that of
U.S. Caucasians. In addition, 22 independent mutation were detected in African
American patients. The patterns of independent germline mutation in 22 African
Americans (and in a combination 34 North American and African Blacks) is similar
to that of U.S. Caucasians. Neither genetic differences between the Black and
Caucasian races nor environmental and cultural differences between South Africa
and the U.S. alter the germline pattern of mutation observed in F9. Hum Mutat
16:372, 2000.
PMID- 11013450
TI - Homocystinuria in the Arab population of Israel: identification of two novel
mutations using DGGE analysis.
AB - This study describes, for the first time, a thorough genetic investigation in
Israeli Arab homocystinuric patients. By using a DGGE methodology and sequencing
we were able to identify the disease causing mutation in all. Of the mutations
that were detected, two are novel: a 785C>G transversion in exon 7 (T262R) and a
5-bp deletion in the 5' of IVS17 including the T in the +2 position that is
crucial for correct splicing (g18327-18331del5). In spite of the highly
consanguineous nature of this population several different mutations were found.
This may suggest that the mutations arose only recently in the population. The
results of our study would enable early prenatal diagnosis, genetic counseling
and screening for the mutations in population at risk. Hum Mutat 16:372, 2000.
PMID- 11013451
TI - Molecular anatomy of CTG expansion in myotonin protein kinase gene among myotonic
dystrophy patients from eastern India.
AB - We have studied the CTG repeat sizes in the DMPK gene and six biallelic markers
which are in complete linkage disequlibrium with Caucasian DM patients, to
identify any common founder haplotype in 30 clinically diagnosed unrelated DM
patients from eastern India. Our results revealed that in 27 patients (90%), CTG
expansion took place on a DraIII(-) - HhaI(-) - Alu(+) - HinfI(+) - Fnu4H I(-) -
TaqI(+) haplotype (haplotype I), similar to what have been published for
Caucasoid and other DM patients. However, in three patients (10%), the expansion
of CTG repeat was on DraIII(+) - HhaI(+) - Alu(+) - HinfI(-) - Fnu4H I(+) - TaqI(
) background (haplotype II), indicating a new haplotype. The distribution of
haplotypes in 52 normal individuals of eastern India revealed that percentage of
haplotypes I and II were 23.1% and 7.7% respectively in normal chromosomes.
Haplotype II is absent among Caucasian DM patients as well as normal individuals
indicating that this particular haplotype may be characteristic of the Indian
population. Hum Mutat 16:372, 2000.
PMID- 11013452
TI - Identification and characterization of two novel mutations that produce acute
intermittent porphyria: A 3-base deletion (841-843delGGA) and a missense mutation
(T35M).
AB - A partial deficiency of Porphobilinogen deaminase (PBGD) is responsible for acute
intermittent porphyria (AIP). AIP is inherited in an autosomal dominant fashion,
and the prevalence in the Argentinean population is about 1:125,000. Here, two
new mutations and two previously reported were found in the PBGD gene in 22
Argentinean AIP patients corresponding to 8 different families. To screen for AIP
mutations in symptomatic patients, genomic DNA isolated was amplified in 6 PCR
reactions, then all coding exons and flanking intronic regions were sequenced.
The novel mutations are 841-843delGGA in exon 14, which results in the loss of
glycine-281 (G281del), and one 104C>T point mutation in the exon 4 (T35M). To
further characterize both novel mutations, the pKK-PBGD construct for the mutant
alleles were expressed in E. coli, the enzymatic activity of the recombinant
proteins were 1% and 4% of the mean level expressed by the normal allele for 841
843delGGA and T35M, respectively. Hum Mutat 16:373, 2000.
PMID- 11013453
TI - Identification of a novel missense mutation L329I in the episodic ataxia type 1
gene KCNA1--a challenging problem.
PMID- 11013454
TI - Homozygous familial hypercholesterolemia: A novel point mutation (W556R) in a
Turkish patient.
PMID- 11013455
TI - Five novel genetic variants in the promoter and coding region of the alpha B
crystallin gene (CRYAB): -652G>A, -650C>G, -249G>C, S41Y, P51L.
PMID- 11013456
TI - Two novel serine repeat length polymorphisms (1043insS and 1043insSS) at exon 23
of the TSC1 gene.
PMID- 11013457
TI - A novel mutation (1653insC) in the thyroid hormone receptor beta in a patient
resistant to thyroid hormone.
PMID- 11013458
TI - Novel single nucleotide polymorphisms (3203A>G and 3204C>T) in the 3' end of the
mitochondrial 16S rRNA gene.
PMID- 11013459
TI - Metachromatic leukodystrophy: a novel mutation (c237delC) and extension of the
haplotype associated with the P426L mutation.
PMID- 11013460
TI - Identification of a novel polymorphism (IVS45+20 C/A) in the splice site of
intron 45 of the ryanodine receptor gene (RYR1).
PMID- 11013461
TI - Delta 469 mutation in the type 3 repeat calcium binding domain of cartilage
oligomeric matrix protein (COMP) disrupts calcium binding.
AB - Cartilage oligomeric matrix protein (COMP/TSP5), a large glycoprotein found in
the territorial matrix surrounding chondrocytes, is the fifth member of the
thrombospondin (TSP) gene family. While the function of COMP is unknown, its
importance is underscored by the finding that mutations in the highly conserved
type 3 repeat domain causes two skeletal dysplasias. Pseudoachondroplasia (PSACH)
and Multiple Epiphyseal Dysplasia, Fairbanks type (EDM1). The type 3 repeats are
highly conserved low-affinity Ca(2+)binding domains that are found in all TSP
genes. This study was undertaken to determine the effects of mutations on calcium
binding and structure of the type 3 repeat domains. Wild-type (WT) and Delta469
recombinant COMP (rCOMP) proteins containing the entire calcium-binding domain
were expressed in E. coli and purified. Equilibrium dialysis demonstrated that WT
bound 10-12 Ca(2+)ions/molecule while Delta469 bound approximately half the
Ca(2+)ions. Circular dichroism (CD) spectrometry had striking spectral changes
for the WT in response to increasing concentrations of Ca(2+). These CD spectral
changes were cooperative and reversible. In contrast, a large CD spectral change
was not observed at any Ca(2+)concentration for Delta469. Moreover, both WT and
Delta469 proteins produced similar CD spectral changes when titrated with Zn(2+),
Cu(2+)and Ni(2+)indicating that the Delta469 mutation specifically affects only
calcium binding. These results suggest that the Delta469 mutation, in the type 3
repeat region, interferes with Ca(2+)binding and that filling of all
Ca(2+)binding loops may be critical for correct COMP protein conformation.
PMID- 11013462
TI - Selective down-regulation of IP(3)receptor subtypes by caspases and calpain
during TNF alpha -induced apoptosis of human T-lymphoma cells.
AB - There are at least three types of inositol 1,4,5-trisphosphate receptor (IP(3)R)
[IP(3)-gated Ca(2+)channels], which are expressed in different cell types and
mammalian tissues. In this study, we have identified three IP(3)R subtypes in
human Jurkat T-lymphoma cells. All three subtypes have a molecular mass of about
260 kDa, and display Ca(2+)channel properties in an IP(3)-dependent manner. We
have also demonstrated that TNFalpha promotes the activity of different proteases
(e.g. caspase-8, caspase-3 and calpain), alters the TCR-mediated Ca(2+)response
and subsequently induces apoptosis in Jurkat cells. During the first 6 h of
incubation with TNFalpha, several IP(3)R subtype-related changes occur (e.g.
proteolysis of IP(3)R subtypes, inhibition of IP(3)binding and impairment of
IP(3)-mediated Ca(2+)flux) concomitantly with an elevation of protease (caspase
8, caspase-3 and calpain) activity. Furthermore, the caspase inhibitor, Z-VAD
fmk, significantly reduces TNFalpha-mediated perturbation of IP(3)R1 and IP(3)R2
(but not IP(3)R3) function; whereas the calpain inhibitor I, ALLN, is capable of
blocking the inhibitory effect of TNFalpha on IP(3)R3 function. These findings
suggest that IP(3)R1 and IP(3)R2 serve as cellular substrates for caspases, and
IP(3)R3 is a substrate for calpain. We propose that the selective down-regulation
of IP(3)R subtype-mediated Ca(2+)function by caspase-dependent and calpain
sensitive mechanisms may be responsible for the early onset of the apoptotic
signal by TNFalpha in human T-cells.
PMID- 11013463
TI - NO-induced modulation of calcium-oscillations in pulmonary vascular smooth
muscle.
AB - The effect of the nitric oxide (NO) donor sodium nitroprusside (SNP) on both
[Ca(2+)](i)and mechanical activity was studied in the rat isolated pulmonary
artery (RPA). In freshly isolated myocytes loaded with 1 microM indo
lacetoxymethyl ester for 30 min, short (40-60 s) application of ATP (100 microM)
or ET-1 (0.1 microM) induced 3-6 cyclic rises in [Ca(2+)](i)(Ca-oscillations) of
decreasing amplitude. Preincubation of cells with SNP (10-250 microM) for 10 min
had no effect on the resting [Ca(2+)](i)value, but progressively abolished the
oscillations. A similar effect was obtained with 8-bromo-cGMP (100-500 microM).
SNP (0.001-100 microM) concentration-dependently relaxed ATP (10 mM, n = 4) and
ET-1 (0.1 microM, n = 4)-precontracted RPA. 1H-[1,2,4]oxadiazolol [4,3,
a]quinoxalin-1-one (ODQ, 10 microM), a potent inhibitor of the cytosolic guanylyl
cyclase, fully reversed the effect of SNP on ATP-induced [Ca(2+)](i)oscillations
as well as on ATP-precontracted RPA. In contrast, N-[2-(methylamino)ethyl]-5
isoquinolinesulfonamide (H8, 10 microM), a potent inhibitor of cGMP-dependent
protein kinase (PKG), did not alter the effect of SNP. Caffeine (5 mM) induced
only one transient [Ca(2+)](i)-increase (n = 24), the amplitude of which was
altered neither by SNP nor by 8-bromo-cGMP. Our results show that the relaxing
effect of NO in RPA is related, at least in part, to its action on the Ca
signalling pathway. NO interacts with inositol trisphosphate pathway without
interacting with the ryanodine-sensitive receptor. Finally, the effect of NO
involves an increase in cGMP but appears independent of activation of PKG.
PMID- 11013465
TI - Dynamic ca(2+)changes in neutrophil phagosomes A source for intracellular
ca(2+)during phagolysosome formation?
AB - An increase in cytosolic Ca(2+)concentration periphagosomally is critical for
phagolysosomal formation and neutrophil elimination of microbes. The
Ca(2+)increase could be achieved through release of Ca(2+)from mobilized
intracellular stores. Alternatively, Ca(2+)that passively enter the phagosome
during phagocytosis could be provided by the phagosome. Intraphagosomal
Ca(2+)changes in single human neutrophils was measured during phagocytosis of
serum opsonized Fura-2-conjugated zymosan particles, using a digital image
processing system for microspectrofluorometry. A decrease in phagosomal
Ca(2+)down to nanomolar concentrations was seen within minutes following
phagosomal closure. Blockage of plasma membrane Ca(2+)channels by econazole
abolished this decrease. The fluorescence properties of Fura-2 zymosan were
retained after phagocytosis and stable to pH changes, reactive oxygen species,
and proteolytic enzymes. We suggest that Ca(2+)ions present in the phagosome
enter the cell cytosol through Ca(2+)channels in the phagosomal membrane,
achieving a localized Ca(2+)rise that is important for phagosome processing.
PMID- 11013464
TI - Calcium signalling in sarcoplasmic reticulum, cytoplasm and mitochondria during
activation of rabbit aorta myocytes.
AB - This study investigated the relationship between cytoplasmic, mitochondrial, and
sarcoplasmic reticulum (SR) [Ca(2+)] in rabbit aorta smooth muscle cells,
following cell activation. Smooth muscle cells were loaded with the Ca(2+)
sensitive fluorescent indicator Mag-Fura-2-AM, and then either permeabilized by
exposure to saponin, or dialyzed with a patch pipette in the whole-cell
configuration to remove cytoplasmic indicator. When the intracellular solution
contained millimolar EGTA or BAPTA, activation of SR Ca(2+)release through
IP(3)or ryanodine receptors induced a decrease in the [Ca(2+)] reported by Mag
Fura-2. However, when EGTA was present at < or =100 microM, the same stimuli
caused an increase in the [Ca(2+)] reported by Mag-Fura-2. The increase in
[Ca(2+)] caused by phenylephrine or caffeine was delayed, and prolonged, with
respect to the cytoplasmic Ca(2+)transient. Evidence is presented that this Mag
Fura-2 signal reflected a rise in mitochondrial [Ca(2+)]. Agents that inhibit
mitochondrial function, such as FCCP or cyanide in combination with oligomycin B,
converted the increase in organelle Mag-Fura-2 fluorescence to a decrease, while
also prolonging the cytoplasmic Ca(2+)transient. There was considerable
similarity between the localization of Mag-Fura-2 fluorescence and the
mitochondria-selective indicator tetramethylrhodamine ethyl ester. Thus, we
propose that there is close functional integration between the SR and
mitochondria in aorta smooth muscle cells, with mitochondria taking up Ca(2+)from
the cytoplasm following cell activation.
PMID- 11013466
TI - Progress in ca(2+)dynamics: small temporal and spatial scales drive macroscopic
dynamics.
PMID- 11013467
TI - Duplicate and salami publications.
PMID- 11013469
TI - The palm print as a sensitive predictor of difficult laryngoscopy in diabetics: a
comparison with other airway evaluation indices.
AB - AIMS: To evaluate the ink impression made by the palm of the dominant hand as a
screening tool for difficult laryngoscopy in diabetic patients. SUBJECTS AND
METHODS: In this prospective study, airway of 50 adult diabetic patients,
undergoing elective surgery under general anaesthesia, was assessed
preoperatively using the common clinical indices such as Modified Mallampati
test, thyromental distance, degree of head extension and a specific index- the
palm print test. Following induction of anaesthesia and neuromuscular relaxation,
laryngoscopy was performed and the laryngoscopic view scored. The sensitivity,
specificity and positive predictive value of each airway evaluation index were
calculated. RESULTS: The incidence of difficult laryngoscopy was 16%. The palm
print test had the highest sensitivity (75%) of all the indices. The thyromental
distance less than six cm had the highest specificity (95.2%) but was least
sensitive (25%). 87% of patients with difficult laryngoscopy had two or more
indices abnormal. CONCLUSION: Though the palm print test was the most sensitive
index of the four indices studied, a better prediction of difficult laryngoscopy
can be achieved by evaluating all the four airway indices preoperatively.
PMID- 11013468
TI - The evaluation of cerebral oxygenation by oximetry in patients with ischaemic
stroke.
AB - AIMS: To evaluate the clinical significance of estimation of the regional
cerebral oxygen saturation (rSO2) in the patients with ischaemic stroke by the
cerebral oximetry during acute, sub-acute and chronic phases. SUBJECTS AND
METHODS: In this prospective study, 24 patients with ischaemic stroke in the
middle cerebral artery territory were included. A detailed clinical examination
and appropriate laboratory investigations were carried out. The rSO2 was
determined by oximetery (INVOS 3100-SD) bilaterally on the first, third, seventh,
and fifteenth days. The blood pressure, the peripheral capillary oxygen
saturation and the arterial blood gas values were noted too. the changes were
evaluated along with Glasgow coma scale (GCS) using unpaired student t-test and
one way ANOVA test. RESULTS: There were significant differences between the rSO2
values in acute, subacute and chronic phases on the side of the lesion (p value <
0.05). The values of oxygen saturation gradually increased throughout the chronic
phase. These values showed a positive correlation with GCS, but the results were
not significant statistically. The rSO2 values were also significantly higher on
the non-lesional side than those on the lesion side in the acute phase (p=
0.0034), the discrepancy disappeared during the sub-acute and chronic phases.
CONCLUSION: Cerebral oximetry can be used as a measure to evaluate the cerebral
oxygenation during the various phases of ischaemic stroke. It has a potential to
serve as a useful marker for detection of cerebral oxygenation imbalances, to
judge the effectiveness of the management and for the follow-up of patients with
ischaemic stroke.
PMID- 11013470
TI - Giant prosthesis for reinforcement of visceral sac for complex bilateral and
recurrent inguinal hernias: a prospective evaluation.
AB - AIMS: To evaluate giant prosthesis for reinforcement of visceral sac (GPRVS) as a
treatment for complex bilateral and recurrent inguinal hernias. SUBJECTS AND
METHODS: The prospective study carried out in a single surgical unit at a
tertiary health care center involved consecutive series of 31 patients with
complex bilateral and recurrent inguinal hernias who underwent GPRVS. All were
men and the mean age was 58 years (range 49-95 years). Factors predicting high
risk for recurrence included a large hernia ( greater, similar5cms, 32%, 10/31
patients), failure of one or more previous repairs (45%, 14/31 patients), chronic
obstructive pulmonary disease (25%, 8/31 patients) and poor muscle tone (70%,
22/31 patients). Operative time, length of postoperative stay, complications and
death were the main outcome measures. RESULTS: Mean -/+ SEM operative time was 65
-/+ 11 minutes (range 45-115 minutes). Mean -/+ SEM length of stay was 3.5 -/+
0.7 days (range 2-5 days). There were 4 minor complications, but no mesh
infections and death. Follow up was obtained for a mean period of 14.6 months
(range 12-23 months); there were no recurrences. CONCLUSION: GPRVS provides a
definitive and safe cure for repair of complex bilateral and recurrent inguinal
hernias because of its simplicity, ease of the procedure, good results and low
recurrence rate.
PMID- 11013471
TI - A study of an epidemic of acute respiratory disease in Jaipur town.
AB - AIM: To detect an association between the sudden epidemic with respiratory
symptoms, and fogging with dichlorovos in Jaipur town and to find out probable
mechanism of causation of the epidemic. SUBJECTS AND METHODS: In this community
based study of the epidemic, house to house survey of households selected using
systematic random sampling was carried out. The incidence in the exposed and
unexposed population, the relative risk and attributable risk were calculated.
RESULTS: The incidence of cases was high (58.9%) in subjects present on roads at
the time of fogging as compared to in those who were inside rooms of the houses
(5.4%) and in those who were not in the locality at that time (1.8%) [Relative
Risk (RR)=32.7 and Attributable Risk (AR)=96.9%]. CONCLUSION: High RR and AR in
the present epidemic indicate strong association between fogging and occurrence
of symptoms. In absence of signs and symptoms of organophosphorus poisoning it
suggests that this could have been due to an inappropriate solvent or defective
functioning of fog generator, leading to generation of an unusual dark fog, that
might have irritated eyes and respiratory tract of exposed residents.
PMID- 11013472
TI - Scleredema adultorum.
AB - Scleredema adultorum is a rare connective tissue disorder reported usually
following streptococcal infection, influenza, measles, and mumps. It has been
reported occasionally following trauma and tuberculous lymphadenitis. This is a
report of scleredema adultorum developing after chicken pox in an eight-year-old
male child. The diagnosis was established by characteristic picture on skin
biopsy using special stain. The patient had a benign course and a spontaneous
recovery in two weeks. The case has been reported as the first case of scleredema
adultorum developing after chicken pox.
PMID- 11013473
TI - An intragastric trichobezoar: computerised tomographic appearance.
AB - A 26-year-old lady presented with a history of abdominal pain and distension
since two months. The ultrasound examination showed an epigastric mass, which was
delineated as a filling defect in the stomach on barium studies. The computerised
tomographic scan showed a gastric mass with pockets of air in it, without post
contrast enhancement. This case highlights the characteristic appearance on
computerised tomography of a bezoar within the stomach, a feature that is not
commonly described in medical literature.
PMID- 11013474
TI - Sprengels deformity: anaesthesia management.
AB - A 28 years old lady presented with Sprengels deformity and hemivertebrae for
Fothergills surgery. Clinically there were no anomalies of the nervous, renal or
the cardiovascular systems. She had a short neck and score on modified Mallapati
test was grade 2. She was successfully anaesthetised using injection Propofol as
a total intravenous anaesthetic agent after adequate premedication with injection
Midazolam and injection Pentazocine. Patient had an uneventful intraoperative and
postoperative course.
PMID- 11013475
TI - Neurofibromatosis-Noonan syndrome or LEOPARD Syndrome? A clinical dilemma.
AB - Neurofibromatosis (NF), Noonan syndrome (NS), and LEOPARD syndrome are all
autosomal dominant conditions, each being a distinct clinical entity by itself.
Rarely, one encounters cases with features of NF and NS and is termed as the
'Neurofibromatosis-Noonan syndrome' (NF-NS). The authors report a clinical
dilemma with major clinical features of the NF-NS syndrome and LEOPARD syndrome
co-existing in the same patient. Also, features of Noonan syndrome and LEOPARD
syndrome are compared with the case reported.
PMID- 11013476
TI - Eisenmenger syndrome in pregnancy.
AB - Maternal mortality in the presence of Eisenmenger syndrome is reported to be 30
to 50% & increases further with associated complications. A case of Eisenmenger
syndrome in pregnancy where the patient progressively deteriorated postpartum &
expired 3 weeks later is reported.
PMID- 11013477
TI - Imaging findings in a giant hepatic artery aneurysm.
AB - A rare case of relatively asymptomatic giant hepatic artery aneurysm of
atherosclerotic aetiology is presented. The importance of imaging findings in the
diagnosis of this condition and the differential diagnosis including the
pertinent literature on the topic is discussed.
PMID- 11013478
TI - Malrotation of the gut manifested during pregnancy.
AB - The diagnosis of intestinal obstruction during pregnancy poses problems, as
vomiting which is an important symptom of the obstruction can be attributed to
hyperemesis of pregnancy and radiological investigation are avoided during this
period. A case of intestinal obstruction due to volvulus resulting from
congenital malrotation of the gut is reported here. The patient first presented
during pregnancy. The case emphasises the need for thorough investigations in a
case of persistent vomiting in pregnancy.
PMID- 11013479
TI - Isolated tuberculous hepatic abscess in a non-immunocompromised patient.
AB - A 38 years old female presented with pain in the epigastrium, jaundice and fever
since one and half month. The computerised tomographic scan of the abdomen
revealed a multiloculated abscess of the left lobe of liver. The pus drained from
the liver abscess at laparotomy showed acid fast bacilli on microscopy. A
detailed search failed to identify any other focus of tuberculous infection. The
case has been reported for the rarity of isolated hepatic tuberculous abscess and
its presentation with jaundice, a rare feature, and to highlight the importance
of microscopic or culture diagnosis in a suspected case of pyaemic abscess.
PMID- 11013480
TI - Giant cell tumour of talar body.
AB - Giant cell tumour (osteoclastoma) of talar bone is a rare entity and is seen more
commonly in the third decade of life. We report this disease entity in a 17-years
old girl. The patient presented with painful swelling of the left ankle with an
osteolytic lesion in the talus on conventional radiographs. Intralesional
curettage and autologous bone grafting was performed following which patient's
pain and swelling disappeared. Complete range of movement at the ankle joint was
regained with minimal restriction at the subtalar joint. There is no evidence of
relapse at six months follow up.
PMID- 11013481
TI - The art and science of presentation: the poster.
PMID- 11013482
TI - Information retrieval in medicine: overview and applications.
PMID- 11013483
TI - The art and science of web-based literature search: the MEDLINE.
PMID- 11013484
TI - Images in medicine: Apert syndrome.
PMID- 11013487
TI - Non-pathology: the bedrock of pathology.
AB - Pathology, also called morbid anatomy, is macroscopically, microscopically, and
molecularly so manifest an array of phenomena that it has compelled medical men
to closely link it up with disease, dis-ease, and death. But there is more than
meets the eye of the morbid anatomists, microscopists, and the molecular
biologists. The obvious science of pathology is governed by numerous abstract,
subtle, non-pathological factors. A pathological phenomenon is subservient to
cosmic noumenon. Such a sea-change allows a newer perspective that cures modern
medicine of many of its dogmas and provides epistemologically valid directions to
research methodologies on the one hand and clinical practices on the other.
PMID- 11013485
TI - Images in radiology: type III growing skull fracture.
PMID- 11013486
TI - Images in pathology: verrucous haemangioma.
PMID- 11013488
TI - Antinuclear antibodies: clinical applications.
AB - One of the common serological hallmarks of autoimmune disorders is the presence
of various autoantibodies in the sera of patients affected by these disorders.
Antinuclear antibodies (ANA) detection is often needed to aid the diagnosis in
several autoimmune disorders. In view of the different methodologies available
for their detection, it becomes essential to understand the advantages and
pitfalls of each procedure. This brief review discusses some methodological
aspects of ANA detection and the clinical relevance of the presence of some of
the autoantibodies found in the sera of patients with autoimmune disorders.
PMID- 11013489
TI - Non-invasive respiratory monitoring in paediatric intensive care unit.
AB - Monitoring respiratory function is important in a Paediatrics Intensive Care Unit
(PICU), as majority of patients have cardio-respiratory problems. Non-invasive
monitoring is convenient, accurate, and has minimal complications. Along with
clinical monitoring, oxygen saturation using pulse oximetry, transcutaneous
oxygenation (PtcO2) and transcutaneous PCO2 (PtcCO2) using transcutaneous
monitors and end-tidal CO2 using capnography are important and routine
measurements done in most PICUs. Considering the financial and maintenance
constraints pulse oximetry with end tidal CO2 monitoring can be considered as
most feasible.
PMID- 11013491
TI - Imagery
PMID- 11013490
TI - Eptifibatide: in the treatment of acute coronary syndromes.
PMID- 11013492
TI - Fos expression in the rat brain and spinal cord evoked by noxious stimulation to
low back muscle and skin.
AB - STUDY DESIGN: Acute noxious stimulation delivered to lumbar muscles and skin of
rats was used to study Fos expression patterns in the brain and spinal cord.
OBJECTIVES: The present study was conducted to determine the differences in Fos
expression in the brain and spinal cord as evoked by stimuli delivered to lumbar
muscles and skin in rats. SUMMARY OF BACKGROUND DATA: Patients with low back pain
sometimes show psychological symptoms, such as quiescence, loss of interest,
decreased activities, appetite loss, and restlessness. The pathway of deep
somatic pain to the brain has been reported to be different from that of
cutaneous pain. However, Fos expression has not been studied in the central
nervous systems after stimulation of low back muscles. METHODS: Rats were
injected with 100 L of 5% formalin into the multifidus muscle (deep pain group; n
= 10) and into the back skin of the L5 dermatome (cutaneous pain group; n = 10).
Two hours after injection, the distribution of Fos-immunoreactive neurons was
studied in the brain and spinal cord. RESULTS: Fos-immunoreactive neurons were
observed in laminae I-V in the spinal cord in the cutaneous pain group, but they
were not seen in lamina II in the deep pain group. In the brain, Fos
immunoreactive neurons were significantly more numerous in the deep pain group
than in the cutaneous pain group in the piriform cortex, the accumbens nucleus
core, the basolateral nucleus of amygdala, the paraventricular hypothalamic
nucleus, the ventral tegmental area, and the ventrolateral periaqueductal gray.
CONCLUSION: The finding that Fos-immunoreactive neurons were absent from lamina
II of the spinal cord in the deep pain group is similar to that of the projection
pattern of the visceral pain pathway. Fos expression in the ventrolateral
periaqueductal gray in the deep pain group may represent a reaction of quiescence
and a loss of interest, activities, or appetite. Furthermore, the detection of
large numbers of Fos-immunoreactive neurons in the core of accumbens nucleus,
basolateral nucleus of amygdala, paraventricular hypothalamic nucleus, and
ventral tegmental area in the deep pain group may suggest a dominant reaction of
dopaminergic neurons to stress, and a different information processing pathway
than from that of cutaneous pain.
PMID- 11013493
TI - Impact response of the intervertebral disc in a finite-element model.
AB - STUDY DESIGN: A three-dimensional nonlinear poroelastic finite-element model of a
vertebra disc was used to analyze the biomechanical effects of impact loading on
the spinal segment. OBJECTIVES: To predict changes in biomechanical parameters
such as intradiscal pressure, dynamic stiffness, stresses in the endplate region,
and the shock-absorbing mechanism of the spine under different impact
duration/loading rates, and to investigate the relation between the rate of
loading and the fracture potential of the vertebral body. SUMMARY OF BACKGROUND
DATA: It is not practical to discern the role of impact duration using
experimental protocols. Analytical studies are better suited to this purpose.
However, previous poroelastic finite-element models of the motion segments have
dealt mostly with creep phenomena. METHODS: A three-dimensional, L3-L4 motion
segment, finite-element model was modified to incorporate the poroelastic
properties of the disc, endplate, and cancellous core, and thus simulate the
shock-absorbing phenomena. The results were analyzed under variable impact
durations for a constant maximum compressive impact load of 3 kN. RESULTS: For a
shorter impact duration and a given F(max), relatively high cancellous core
pressure was generated as compared with a case of long impact duration, although
the amount of impulse was increased. In contrast, relatively constant pore
pressures were generated in the nucleus regardless of the impact duration. The
changes in spinal segment stiffness as a function of impact duration indicated
that for a shorter duration of impact, high dynamic stiffness increases the
stability of the spinal segment against the impact load. However, the
corresponding increase in stresses within the vertebral body and endplate may
produce fractures. CONCLUSIONS: The finite-element technique was used to address
the role of impact duration in producing trauma to the spinal motion segment.
Within the limitations of the model, the results suggest that fractures are
likely to occur under shorter impact duration conditions. Depending on the
strength of the region, a fracture may be initiated in the endplate region or the
posterior wall of the cortical shell. The nucleus pressure is independent of the
impact duration and depends only on the magnitude of the impact force.
PMID- 11013494
TI - Patient characteristics and patterns of use for lumbar spine radiographs: results
from the Veterans Health Study.
AB - STUDY DESIGN: Longitudinal data from the Veterans Health Study, an observational
study of male patients receiving Veterans Administration ambulatory care, were
analyzed. OBJECTIVE: To identify patient characteristics that predict different
patterns in the use of lumbar spine radiographs. SUMMARY AND BACKGROUND DATA: In
this study, 401 patients with low back pain receiving ambulatory care services in
four Veterans Administration outpatient clinics in the greater Boston area were
followed for 12 months. METHODS: Participants were mailed the Medical Outcome
Study Short Form Health Survey and participated in scheduled interviews that
included the completion of a low back questionnaire, a comorbidity index, and a
straight leg raising test. Four groups of patients were defined according to the
patterns of use for lumbar spine radiographs: prior use, repeat use, no use, and
new use of lumbar spine radiographs. These groups were compared in terms of
sociodemographics, comorbid conditions, low back pain intensity, radiating leg
pain, straight leg raising, Medical Outcome Study Short Form Health Survey
scores, and low back disability days. RESULTS: The patients with new lumbar spine
radiographs showed worse physical and psychological distress than the
participants in the other three groups. In contrast, the patients with no lumbar
spine radiographs reported minor physical impairment. Compared with patients who
had no repeat radiographs, patients with repeat lumbar spine radiographs had
similar scores on physical health, but they showed worse scores of mental health.
CONCLUSIONS: Both physical and psychological factors contribute to having new
radiographic examinations, whereas psychological factors have increased
importance in the repeat use of roentgenographic examinations. Repeat radiographs
appear to be overused, judging by the severity of physical impairment as measured
by low back pain intensity, the Medical OutcomeStudy Short Form Health Survey,
and disability days.
PMID- 11013495
TI - Patient-oriented outcomes from low back surgery: a community-based study.
AB - STUDY DESIGN: This study used a prospective cohort design. OBJECTIVE: To examine
factors associated with favorable self-reported patient outcomes 1 year after
elective surgery for degenerative back problems. SUMMARY OF BACKGROUND DATA: Many
previous studies addressing the results of low back surgery have been conducted
in academic institutions or by single surgeons. As part of a quality improvement
effort, surgeons in private practice led a community-based outcomes management
project in Washington State. METHODS: Patients ages 18 and older with the
following diagnoses were eligible for the study: degenerative changes, herniated
disc, instability, and spinal stenosis. Nine orthopedists and neurosurgeons
enrolled a total of 281 patients. Participants were asked to complete baseline
and 1-year follow-up surveys. Data concerning diagnoses, clinical signs, and
operative procedures were provided by the surgeons. The researchers examined
sociodemographic characteristics, self-reported symptoms before surgery,
preoperative clinical signs, diagnoses, and operative procedures associated with
three primary outcomes: better functioning, improved quality of life, and overall
treatment satisfaction. RESULTS: Follow-up surveys were completed by 236 (84%) of
the enrolled patients. Approximately two thirds of the study participants
reported much better functioning (65%), a great quality of life improvement
(64%), and a very positive perspective about their treatment outcome (68%). The
following variables were associated with worse patient outcomes: older age,
previous low back surgery, workers' compensation coverage, and consultation with
an attorney before surgery. Patients undergoing a fusion procedure were more
likely to report good outcomes. CONCLUSIONS: The authors' experience indicates
that community-based outcomes data collection efforts are feasible and can be
incorporated into usual clinical practice. The study results indicate that
compensation payments and litigation are two important predictors of poor
outcomes after low back surgery in community practice. Because of small numbers,
varied diagnoses, and possible selection bias, the findings with respect to
fusion should be interpreted cautiously.
PMID- 11013496
TI - Loss of sagittal plane correction after removal of spinal implants.
AB - STUDY DESIGN: A retrospective review of a clinical series was performed.
OBJECTIVES: To evaluate the incidence of adult patients who experienced spinal
collapse after spinal implant removal after a long spinal arthrodesis, and to
assess the various factors that may influence the likelihood of collapse after
implant removal. SUMMARY OF BACKGROUND DATA: Published reports describing the
benefits or complications of spinal implant removal do not exist. Spinal implant
removal, often considered a benign procedure, is even required by the Food and
Drug Administration (FDA) for certain implants. METHODS: The medical records and
radiographs of 116 consecutive adult patients with long posterior instrumented
fusions (>5 segments) were reviewed. The information obtained included original
diagnosis, patient age, number of previous surgeries before implant removal,
levels of anterior and posterior fusion, time from fusion to implant removal,
time from implant removal to failure, and reason for hardware removal.
Radiographs also were assessed including scoliosis, lordosis, and kyphosis
measurements before implant removal, after hardware removal, after failure, and
after revision surgery. RESULTS: Of 116 patients, 14 underwent spinal implant
removal. Most of these patients reported prominent implants either proximally in
the thoracic spine or distally in the ilium (Galveston technique). Of these 14
patients, 4 experienced increased pain and collapse after implant removal despite
thorough intraoperative explorations demonstrating solid fusion. CONCLUSIONS:
Spinal implant removal after long posterior fusion in adults may lead to spinal
collapse and further surgery. Removal of instrumentation should be avoided or
should involve partial removal of the prominent implant.
PMID- 11013497
TI - Deep wound infections after neuromuscular scoliosis surgery: a multicenter study
of risk factors and treatment outcomes.
AB - STUDY DESIGN: A retrospective case-control study evaluating risk factors for
infection, causative organisms, and results of treatment in patients with
cerebral palsy or myelomeningocele who underwent fusion for scoliosis was
performed. OBJECTIVES: To identify risk factors for infection, and to
characterize the infections in terms of infecting organisms and response to
treatment. SUMMARY OF BACKGROUND DATA: No previous studies have analyzed risk
factors or causative organisms, nor have they indicated results of treatment for
infections in this group of patients. METHODS: After a 10-year retrospective
review of 210 surgically treated patients, deep wound infections developed in 16
patients with myelomeningocele and 9 patients with cerebral palsy. These patients
were studied extensively for possible risk factors, along with 50 uninfected
patients matched for age, diagnosis, and year of surgery. Statistical testing was
performed to identify risk factors. The courses of the infections were
characterized in terms of organisms isolated and response to treatment. Treatment
was performed in a stepwise fashion and classified in terms of the most
successful step: debridement and closure, granulation over rods, or
instrumentation removal. RESULTS: Of the 10 risk factors tested, 2 were found to
be significant: degree of cognitive impairment and use of allograft. Findings
showed that 52% of the infections were polymicrobial. Gram-negative organisms
were isolated as commonly as gram-positive organisms. The most common organisms
were coagulase-negative Staphylococcus, Enterobacter, Enterococcus, and
Escherichia coli.- Debridement and closure were successful in 11 of 25 patients
with deep wound infection. Of the 14 patients with infection not resolved by
serial debridements and closure, 2 were managed successfully by allowing the
wound to granulate over rods, and 7 required rod removal for persistent wound
drainage. There were three symptomatic pseudarthroses. Infections resulting from
gram-positive organisms were most often managed successfully with debridement and
closure (P = 0.012). CONCLUSIONS: Patients with cerebral palsy or
myelomeningocele who have severe cognitive impairment, and those who received
allograft may be at increased risk for infection. Infections are more often
polymicrobial and caused by gram-negative organisms than is typical for elective
orthopedic procedures. This suggests an enteric source. Treatment with
debridement and closure was not always successful. Patients in whom infection
develops are then at increased risk for pseudarthrosis.
PMID- 11013498
TI - Surface electrode somatosensory-evoked potentials in spinal surgery: implications
for indications and practice.
AB - STUDY DESIGN: A retrospective study of 442 major spinal operations with spinal
cord monitoring performed in a University Hospital between 1982 and 1992 was
performed. OBJECTIVES: To assess the reliability of the authors' method for
monitoring by somatosensory-evoked potential recording, to determine criteria for
intraoperative corrective action, and to redefine the need for the wake-up test.
SUMMARY OF BACKGROUND DATA: The routine use of somatosensory-evoked potential
monitoring in spinal surgery remains controversial. In Nottingham, the authors
have used a method of recording from either scalp or high cervical electrodes.
METHODS: The recordings and outcomes of all monitored spinal operations between
the years 1982 and 1992 were reviewed. RESULTS: In 442 procedures, 23 technical
failures (no reliable monitoring) occurred. Most technical failures were in
patients with severe preoperative neurology, identifiable by somatosensory-evoked
potential recording before operation. In the remaining 419 procedures, a
significant intraoperative change in response occurred in 70 procedures (16.7%).
Using the definitions of the American EEG Society, the authors identified 10 true
positives and 60 false-positives. There were no false-negatives. A wake-up test
was performed if an amplitude drop greater than 50% from baseline value persisted
after attempts to correct any possible identifiable intraoperative cause. This
occurred in only 21 patients (5%). In the true-positive group, somatosensory
evoked potential recordings remained persistently abnormal despite an apparently
normal subsequent wake-up test. The sensitivity of the method according to
current definitions was 100% and the specificity 85.33%. CONCLUSIONS: Modified
guidelines are needed for routine intraoperative use of somatosensory-evoked
potential monitoring in spinal surgery. Such guidelines should avoid the term
"false-positive" as currently defined and concentrate on the causative analysis
of abnormal responses that warn of critical spinal cord dysfunction before that
becomes irreversible and allow for appropriate action. Information from this
monitoring method alerted the surgeon to the possible need for corrective action
in an additional 9.78% of the reported patients, who traditionally would have
been regarded as false-positives. A wake-up test still is indicated in patients
with persistent suppression of their somatosensory-evoked potential despite
correction of any identifiable cause and in cases of technical failure. The
current method proved flexible, versatile, and reliable for future use.
PMID- 11013499
TI - One-year prevalence of low back pain in two Swiss regions: estimates from the
population participating in the 1992-1993 MONICA project.
AB - STUDY DESIGN: A cross-sectional survey was performed. OBJECTIVE: To estimate the
extent of low back pain as a public health problem. SUMMARY OF BACKGROUND DATA:
Health surveys converge on very high estimates of low back pain in general
populations, but few studies have included severity criteria in their definition
and conclusions. Because it is unlikely that interventions will influence the
prevalence of minimal and infrequent symptoms, greater attention should be paid
to characteristics of low back pain that indicate some impact on the life of
survey respondents. METHODS: Two regions participated in the MONICA (MONitoring
of trends and determinants in CArdiovascular disease) project in Switzerland.
Participants randomly selected from the general population completed a standard
self-administered questionnaire on cardiovascular risk factors. A special section
on low back pain was added in the third (1992-1993) MONICA survey and completed
by 3227 participants. RESULTS: A regional difference found in the 12-month
prevalence rate disappeared with the inclusion of severity criteria. Low back
pain over more than seven cumulated days was reported among men by 20.2% (age
range, 25-34 years) to 28.5% (age range, 65-74 years), respectively, among women
by 31.1% to 38.5%. Similar rates of reduction in activity (professional,
housekeeping, and leisure time) and medical consultation (conventional and
nonconventional) motivated by low back pain characterized the two participating
regions. The cumulative duration of pain was related to all the indicators
showing the impact of low back pain on everyday life. CONCLUSIONS: Determining
the cumulative duration of low back pain over the preceding year is a
straightforward task, and a cutoff at 1 week seems appropriate for distinguishing
between low- and high-impact low back pain.
PMID- 11013500
TI - Socioeconomic factors and disability retirement from back pain: a 1983-1993
population-based prospective study in Norway.
AB - STUDY DESIGN: A prospective observational study with an 11-year follow-up period
was performed. OBJECTIVE: To investigate the influence of education and
socioeconomic position on the incidence of permanent disability retirement from
back pain. SUMMARY OF BACKGROUND DATA: Early retirement because of back pain is
the extreme end point of a disabling process that is a great burden to the
individual and costly for the society. Groups of employees at particular risk for
permanent back pain disability need to be identified. METHODS: All employed men
and women in Norway between the ages of 20 and 53 years in 1980 were included (n
= 1,333,556). Outcome measures were disability retirement from inflammatory back
pain (ICD-9 code 720) and noninflammatory back pain (ICD-9 codes 721 to 724).
RESULTS: The 11-year cumulative incidence was 0.15% (n = 1990) for disability
retirement from inflammatory back pain and 1. 64% (n = 21,829) for
noninflammatory back pain and was somewhat higher in women than in men. Each year
of formal education was independently associated with decreased risk for
disability retirement from noninflammatory back pain (odds ratio [OR] = 0.78; 95%
confidence interval [CI] = 0.77-0.79) and from inflammatory back pain (OR = 0.83;
95% CI = 0.81-0.86). Whereas disability from inflammatory back pain was
moderately associated with socioeconomic status, there was a consistent upward
trend in the association between disability retirement from noninflammatory back
pain and lower socioeconomic position. The OR for unskilled workers was 3.1 (95%
CI = 2.6-3.7) for men and 2.1 (95% CI = 1.7-2.5) for women, as compared with that
of higher professionals. Stepwise analyses suggest that the effect of education
is not mediated by socioeconomic status. CONCLUSIONS: The consistent upward trend
in the relation of disability retirement to lower levels of education and
socioeconomic position, even for inflammatory back pain, shows that factors
related to the occupational and social environment play an important role in the
disabling process. The stepwise, monotonic relation between socioeconomic
position and disability retirement from back pain, even at the higher end of the
socioeconomic scale, suggests that the relation between social class and back
pain disability cannot be explained solely in terms of manual versus nonmanual
jobs.
PMID- 11013501
TI - Differences in repositioning error among patients with low back pain compared
with control subjects.
AB - STUDY DESIGN: Trunk repositioning error was measured in 20 patients with chronic
low back pain and 20 control subjects. OBJECTIVES: To measure trunk repositioning
error as a method of measuring proprioception of the low back and to compare
trunk repositioning error in patients with low back pain and in control subjects.
SUMMARY OF BACKGROUND DATA: Although many current low back pain rehabilitation
programs incorporate proprioceptive training, very little research has been
performed on proprioception of the low back. METHODS: While standing with the
legs and pelvis immobilized, the subject bent the trunk to a predetermined target
position and then attempted to replicate the position. Repositioning error was
calculated as the absolute difference between the actual target position and the
subject-perceived target position. The multiple target positions in the frontal
and sagittal planes were tested. Trunk position was measured with a 3Space
Tracker, which analyzes the three-dimensional position of the body. RESULTS:
Repositioning error in patients with low back pain was significantly higher than
that of control subjects in flexion, and significantly lower than that of control
subjects in extension. CONCLUSIONS: The increase in repositioning error of
patients with low back pain during flexion implies that some aspects of
proprioception are lost in patients with low back pain. The decrease in
repositioning error in patients with low back pain in extension is not as easily
explained, but could possibly be caused by increased activation of
mechanoreceptors in facet joints.
PMID- 11013502
TI - Functional restoration versus outpatient physical training in chronic low back
pain: a randomized comparative study.
AB - STUDY DESIGN: A randomized parallel-group comparative trial with a 1-year follow
up period was performed. OBJECTIVE: To compare the effect of a comprehensive
functional restoration program involving intensive physical training, ergonomic
training, and behavioral support (39 hours per week for 3 weeks) with the effect
of outpatient intensive physical training (1.5 hours three times per week for 8
weeks). SUMMARY OF BACKGROUND DATA: Nonrandomized studies conducted in the United
States favor functional restoration for patients with chronic low back pain. Two
previously reported randomized studies from the authors' Back Center in
Copenhagen concur with this recommendation, although the positive effects in one
of the studies had faded out after 2 years. Randomized functional restoration
studies in Canada and Finland have failed to demonstrate any substantive effect.
METHODS: Initially, 138 patients with chronic low back pain were included in the
current study. They then were randomized to either functional restoration (n =
64) or outpatient intensive physical training (n = 74). Of the initial 138
patients, 11 never started (5 and 6, respectively); 21 dropped out during
treatment (8 and 13); and 7 of the graduates did not take part in the 1-year
follow-up evaluation (3 and 4). The conclusions were drawn from the 99 patients
(48 and 51, respectively) who graduated and participated in a 1-year follow-up
evaluation. The median age of the patients was 42 years (range, 21-55 years) The
female-to-male ratio was 68 to 31, and the median sick leave days during the
preceding 3 years was 180 (range, 0-1080 days). The average back pain was rated
5.5 on a scale of 0 (no pain) to 10 (maximal pain). For these variables, there
were no important differences between the groups. However, the functional
restoration group tended to be more capable of work at baseline (58% vs 42%; P =
0.09). RESULTS: At the 1-year follow-up evaluation, overall assessment favored
functional restoration. Otherwise, no significant differences were observed
regarding work capability, sick leave for those at work, health care
contacts,back pain, leg pain, or self-reported activities of daily living.
CONCLUSIONS: Only in terms of overall assessment, the functional restoration
program was superior to a comparatively short time-consuming outpatient physical
training program. DISCUSSION: It may be that lower economic benefits during sick
leave in the United States lead to favorable results from functional restoration
programs, whereas greater benefits in Canada, Finland, and Denmark result in
different conclusions. Finally, it may be that the difference in results across
studies points simply to whether the studies were randomized.
PMID- 11013503
TI - Nonsteroidal anti-inflammatory drugs for low back pain: a systematic review
within the framework of the Cochrane Collaboration Back Review Group.
AB - STUDY DESIGN: A systematic review of randomized and double-blind controlled
trials was performed. SUMMARY OF BACKGROUND DATA: Nonsteroidal anti-inflammatory
drugs are the most frequently prescribed medications worldwide and are widely
used for patients with low back pain. OBJECTIVES: To assess the effects of
nonsteroidal anti-inflammatory drugs in the treatment of nonspecific low back
pain with or without radiation, and to assess which type of nonsteroidal anti
inflammatory drug is most effective. METHODS: For this study, the Cochrane
Controlled Trials Register, Medline and Embase, and reference lists of articles
were searched. Two reviewers blinded with respect to authors, institution, and
journal independently extracted data and assessed the methodologic quality of the
studies. If data were considered clinically homogeneous, a meta-analysis was
performed. If data were considered clinically heterogeneous, a qualitative
analysis was performed using a rating system with four levels of evidence:
strong, moderate, limited, and no evidence. RESULTS: This review involved 51
trials and 6057 patients. Of these trials, 16 (31%) were of high quality. The
pooled relative risk for global improvement after 1 week was 1.24 (95% confidence
interval [CI] = 1.10-1.41), and for additional analgesic use was 1.29 (95% CI =
1.05-1.57), indicating a statistically significant but small effect in favor of
nonsteroidal anti-inflammatory drugs as compared with a placebo. The results of
the qualitative analysis showed that there is conflicting evidence (Level 3) that
nonsteroidal anti-inflammatory drugs are more effective than paracetamol for
acute low back pain, and that there is moderate evidence (Level 2) that
nonsteroidal anti-inflammatory drugs are not more effective than other drugs for
acute low back pain. There is strong evidence (Level 1) that various types of
nonsteroidal anti-inflammatory drugs are equally effective for acute low back
pain. CONCLUSIONS: The evidence from the 51 trials included in this review
suggests that nonsteroidal anti-inflammatory drugs are effective for short-term
symptomatic relief in patients with acute low back pain. Furthermore, there does
not seem to be a specific type of nonsteroidal anti-inflammatory drug that is
clearly more effective than others. Sufficient evidence on chronic low back pain
still is lacking.
PMID- 11013504
TI - Primary lumbosacral stability after open posterior and endoscopic anterior fusion
with interbody implants: a roentgen stereophotogrammetric analysis.
AB - STUDY DESIGN: After posterior stabilization of the spondylolytic lumbosacral
level, mobility of the fused vertebrae could be studied before and after an
additional anterior endoscopic interbody fusion using roentgen
stereophotogrammetric analysis. OBJECTIVE: To determine the in vivo primary
lumbosacral stability of additional anterior interbody fusion after
transpedicular screw fixation. SUMMARY OF BACKGROUND DATA: In vitro studies
indicate a significant decrease in segmental motion after pedicle screw fixation
and additional anterior fusion. Roentgen stereophotogrammetric studies
demonstrate the adequacy of transpedicular lumbar instrumentation in
posterolateral fusions. There are no studies examining the effect of additional
anterior interbody fusion after posterior instrumentation in vivo. METHODS: In
this study, 15 patients with low-grade spondylolisthesis at L5-S1 underwent a two
stage open posterior and endoscopic anterior lumbar fusion using carbon fiber
(Brantigan I/F) cages. At surgery, tantalum markers were implanted into the fifth
lumbar (L5) and the first sacral (S1) vertebra. All the patients were examined by
roentgen stereophotogrammetric analysis after the first and second surgical
procedures. RESULTS: After implantation of the posterior pedicle system only, the
mean intervertebral mobility determined by roentgen stereophotogrammetric
analysis was 0.23 mm in the transverse (x), 0.54 mm in the vertical (y), and 1.2
mm in the sagittal (z) axes. After additional anterior endoscopic fusion with
carbon cages, the remaining translation between the fused segment L5/S1 decreased
to 0.17 mm in the x, 0.16 mm in the y, and 0.44 mm in the z axes. CONCLUSION:
Anterior endoscopic lumbosacral fusion significantly increases the primary
stability of the posterior fusion with a pedicle system in two axes of motion.
PMID- 11013505
TI - Spinal reflex attenuation associated with spinal manipulation.
AB - STUDY DESIGN: This study evaluated the effect of lumbosacral spinal manipulation
with thrust and spinal mobilization without thrust on the excitability of the
alpha motoneuronal pool in human subjects without low back pain. OBJECTIVES: To
investigate the effect of high velocity, low amplitude thrust, or mobilization
without thrust on the excitability of the alpha motoneuron pool, and to elucidate
potential mechanisms in which manual procedures may affect back muscle activity.
SUMMARY OF BACKGROUND DATA: The physiologic mechanisms of spinal manipulation are
largely unknown. It has been proposed that spinal manipulation may reduce back
muscle electromyographic activity in patients with low back pain. Although
positive outcomes of spinal manipulation intervention for low back pain have been
reported in clinical trials, the mechanisms involved in the amelioration of
symptoms are unknown. METHODS: In this study, 17 nonpatient human subjects were
used to investigate the effect of spinal manipulation and mobilization on the
amplitude of the tibial nerve Hoffmann reflex recorded from the gastrocnemius
muscle. Reflexes were recorded before and after manual spinal procedures.
RESULTS: Both spinal manipulation with thrust and mobilization without thrust
significantly attenuated alpha motoneuronal activity, as measured by the
amplitude of the gastrocnemius Hoffmann reflex. This suppression of motoneuronal
activity was significant (P < 0.05) but transient, with a return to baseline
values exhibited 30 seconds after intervention. CONCLUSIONS: Both spinal
manipulation with thrust and mobilization without thrust procedures produce a
profound but transient attenuation of alpha motoneuronal excitability. These
findings substantiate the theory that manual spinal therapy procedures may lead
to short-term inhibitory effects on the human motor system.
PMID- 11013506
TI - The effect of neuromuscular blockade on pedicle screw stimulation thresholds.
AB - STUDY DESIGN: Nerve root stimulation thresholds were studied relative to the
level of neuromuscular blockade in patients undergoing lumbar decompression
surgery. OBJECTIVES: To determine what levels of intraoperative neuromuscular
blockade can be used during pedicle screw stimulation. BACKGROUND DATA: Previous
studies of intraoperative pedicle screw stimulation thresholds have failed to
determine the effect of neuromuscular blockade on the stimulation threshold.
METHODS: Twenty-one roots in 10 patients undergoing lumbar decompression surgery
were studied at different levels of neuromuscular blockade. Ninety-five nerve
root thresholds were determined relative to level of blockade. RESULTS:
Neuromuscular blockade below 80% provides nerve root thresholds similar to
thresholds without blockade. CONCLUSIONS: Neuromuscular blockade should be less
than 80% when using pedicle screw electrical stimulation testing.
PMID- 11013508
TI - Follow-up evaluation of resected lumbar vertebral chordoma over 11 years: a case
report.
AB - STUDY DESIGN: A case report with an 11-year follow-up assessment after resection
and reconstruction for lumbar chordoma is given. The literature relevant to this
topic is reviewed. OBJECTIVES: To report the long-term outcome in a case of
lumbar chordoma, to review the literature on vertebral chordoma, and to outline
the rationale for surgical resection in such cases. SUMMARY OF BACKGROUND DATA:
Chordoma is a malignant bone tumor that grows slowly, often recurs locally, and
metastasizes late. Although different treatment approaches exist, including
radiation and surgery, the only curative treatment is early and complete surgical
excision of the tumor. Immediate spinal stability must be achieved with
appropriate replacement or bone graft with rigid fixation. METHODS: The 11-year
follow-up evaluation of a 42-year-old woman with L3 and L4 vertebral body
chordoma treated with complete removal, femoral shaft allograft replacement,
fusion, and rigid metal fixation is reported. The patient was observed with
serial physical examinations, radiographs, and laboratory studies over 11 years.
RESULTS: At this writing, 11 years after the resection of the L3 and L4 chordoma,
the patient is asymptomatic without evidence of recurrence or metastasis.
CONCLUSIONS: As reported, vertebral chordomas are not curable, but the authors'
experience contradicts this. The surgeon should aim at a wide, or at least a
marginal, excision followed by a stable reconstruction.
PMID- 11013507
TI - Respiratory failure in postpneumonectomy syndrome complicated by thoracic
lordoscoliosis: treatment with prosthetic implants, partial vertebrectomies, and
spinal fusion.
AB - STUDY DESIGN: This study investigated the case of a 17-year-old girl with
postpneumonectomy syndrome, complicated by a thoracic lordoscoliosis, who was
successfully treated with prosthetic implants, partial vertebrectomies, and
anteroposterior spinal fusion. OBJECTIVE: To report a unique case and describe
the authors' method of treatment. SUMMARY OF BACKGROUND DATA: Postpneumonectomy
syndrome is an uncommon complication of pneumonectomy. Many case reports describe
successful treatment with insertion of prosthetic implants into the empty
hemithorax to shift the mediastinum to its original position. Thoracic
lordoscoliosis reportedly has contributed to pulmonary compromise, but no cases
have shown its occurrence in the setting of postpneumonectomy syndrome. METHODS:
The patient was observed at the National Children's Hospital in Tokyo, referred
to Children's Hospital in Los Angeles, California for surgical correction, and
followed in Tokyo for the next year. RESULTS: Two prosthetic implants with an
injection port for further expansion were positioned in the right hemithorax to
restore the mediastinum to its normal position. Anterior discectomies, partial
vertebrectomies, and fusion of T5-T10 was performed concurrently. Then 5 days
later, posterior spinal fusion of T1-T12 with instrumentation and bone graft were
performed to correct the thoracic lordoscoliosis and increase the chest cavity
space. At 1 month after the surgery, the patient was extubated after being
ventilator dependent for 5 months. At the time of operation, the girl was
ventilator dependent and nonambulatory, but 1 year later could participate in all
activities of daily living without any oxygen supplementation. CONCLUSIONS:
Postpneumonectomy syndrome can be treated successfully with prosthetic implants
to restore the normal position of the mediastinum. Thoracic lordoscoliosis can
complicate the syndrome and may be corrected to help restore normal pulmonary
function.
PMID- 11013509
TI - Contralateral spondylolysis and fracture of the lumbar pedicle in an elite female
gymnast: a case report.
AB - STUDY DESIGN: The case of an elite female gymnast whose pathology started in her
12th year and whose evolution has been exceptional is reported. OBJECTIVE: To
present a fracture of the right lumbar pedicle showing complete spontaneous
consolidation despite gymnastic practice 15 hours a week. SUMMARY OF BACKGROUND
DATA: Lumbar pain, which has an incidence of approximately 75% among young
athletes, often results from diseases of the posterior arch of vertebrae in
gymnasts, including spondylolysis. The association between unilateral
spondylolysis and fracture of the contralateral lumbar pedicle in young athletes
is poorly described. METHODS: An elite young female gymnast underwent clinical
examination and lumbar radiographs (as systematically required by the French
Federation for high-level gymnasts) from 1994 to 1997 to join a sports program in
gymnastics. RESULTS: Clinical examination and lumbar radiographs systematically
required of an asymptomatic female gymnast allowed the condensation of the right
pedicle to be observed before lysis of the left isthmus of L5 in 1994, unilateral
lysis of the left isthmus of L5 in 1995, a right pedicular fracture of L5 in
1996, and healing of the pedicular fracture in 1997. CONCLUSION: Inconsistency
between radiographs and clinical observations can be noted, and spontaneous
consolidation of pedicular fractures can occur despite the practice of the
gymnastics 15 hours a week.
PMID- 11013510
TI - Spine update: antimicrobial prophylaxis in spine surgery: basic principles and
recent advances.
PMID- 11013511
TI - Early intervention for back-injured nurses at a large hospital.
PMID- 11013512
TI - Luque trolley and convex epiphysiodesis in the management of infantile and
juvenile scoliosis.
PMID- 11013513
TI - The measurement of static pelvic skeletal asymmetry.
PMID- 11013514
TI - Revised Oswestry Disability questionnaire.
PMID- 11013515
TI - Cause of idiopathic scoliosis.
PMID- 11013516
TI - A computer simulation for the entry-level RN: enhancing clinical decision making.
AB - Staff development educators struggle to prepare today's entry-level RN for
effective decision making in a new healthcare climate that demands both skill and
expertise with patients with high acuity levels. The clinical decision making
simulator is an innovative approach to teaching and learning decision-making
skills. The authors discuss the development and use of a computer simulation that
provides repeated opportunities for clinical decision making for the newly
licensed nurse without jeopardizing patient safety.
PMID- 11013517
TI - Development of a discharge planning mentorship program.
AB - Discharge planning coordinators at a tertiary medical center developed a
Discharge Planning Mentorship Program. The group established the educational
program to support the autonomy of the staff primary nurse in the discharge
planning component of professional practice. To establish the program, the
discharge planning coordinators used the underlying principle of "CollaMentoach."
The term is an acronym combining the three core concepts of collaboration,
mentoring, and coaching. Program planning and marketing, participant selection,
curriculum development, and curriculum evaluation are included to guide staff
development specialists and nurse managers in the formulation of a program to
enhance staff nurse discharge planning skills.
PMID- 11013518
TI - Providing mandatory safety information to hospital employees: finding a way that
is fast, fun, and effective.
AB - An interdisciplinary team of medical center employees transformed a 2-hour
mandatory safety class into a 15-minute interactive marathon. The marathon,
coupled with a self-learning packet and posttest, not only measured cognitive
knowledge but included a component of competence demonstration. The information
included 10 specific safety topics pertinent to all medical center employees
including those in 12 physician satellite offices. This educational format has
proven successful in providing safety information that is fast, fun, and
effective.
PMID- 11013519
TI - Facilitating critical thinking.
AB - Supporting staff to think effectively is essential to improve clinical systems,
decrease errors and sentinel events, and engage staff involvement to refine
patient care systems in readiness for new care-delivery models that truly reflect
the valued role of the RN. The authors explore practical methods, based on
current research and national consulting experience, to facilitate the
development of mature critical thinking skills. Assessment tools, a sample agenda
for formal presentations, and teaching strategies using behavioral examples that
make the important and necessary link of theory to reality are discussed in the
form of a critical thinking test as well as a conceptual model for application in
problem solving.
PMID- 11013520
TI - Integrating technology and traditional teaching methods to stimulate different
cognitive styles in a critical care course.
AB - This article describes a method of instruction designed to stimulate many
different cognitive styles in an RN critical care course. The class met on Friday
evenings after many of the participants had just completed their workweek.
Developing a stimulating classroom experience was imperative to counter the
effects of fatigue felt by many of the nurses. A combination of technology and
traditional teaching methods was used to facilitate as many different cognitive
styles as possible in a single class period. The PowerPoint computer program was
used to provide vivid visual representation of the class content as it was
presented through a combination of lecture, concept mapping, and case study.
PMID- 11013521
TI - A CQI approach to evaluating continuing education: processes and outcomes.
AB - Traditional methods of evaluating continuing nursing education have focused on
end-of-session feedback and/or testing related to the learning experience. A
continuous quality improvement (CQI) framework and associated statistical process
control tools provide an alternative approach to assessing both processes and
outcomes of continuing nursing education. One implementation example demonstrates
the value of this approach. The CQI model offers an exciting option to continuing
education/staff development educators looking for creative and beneficial ways to
evaluate educational activities.
PMID- 11013522
TI - Human responses to pain: a global perspective.
PMID- 11013523
TI - Pain as a mutual experience for patients, nurses and families: unique
international perspectives from the Peoples' Republic of China, the United
States, Malawi and Spain.
AB - This article shares findings from a descriptive research study that explored pain
recognition, pain intervention and perceived pain relief in laboring women,
children and older adult patients from four very different countries. Researchers
included co-investigators from each site and a team of more than 20 nurses from
China, the United States, Malawi and Spain. This international, multi-site study
investigated specific aspects of the phenomena of pain which are known to be of
interest to nurses internationally. Critical issues related to feasibility of
this study depended, in large part, on the ability of principle investigators to
have access to a sample comprised of sub-samples of nationally different subjects
that would represent the population of interest. Access to the four study
countries was made possible through professional relationships previously
developed by either one of the principal or co-investigators.
PMID- 11013524
TI - Pain as a mutual experience for patients, nurses and families: a perspective from
Shanghai, China.
AB - The author of this article visited China for the purpose of helping the faculty
of the School of Nursing learn research skills by participating in research--a
kind of learn by doing. Both investigators had conducted quantitative studies in
the US--one with children and one with adults--that were adapted for use in
China. Seeking to also include a qualitative study, the investigators explored
several possible research areas. Because pain is a universal phenomena, it was
chosen as the subject for the study using the qualitative methodology reported in
the first part of this article.
PMID- 11013526
TI - Pain as a mutual experience for patients, nurses and families: a perspective from
Lilongwe, Malawi.
AB - The data for this study were collected in the Republic of Malawi (formerly
Nyasaland), a small country in South Central Africa. Data were collected by
registered nurses who were senior students in the first class of registered nurse
midwives enrolled in a baccalaureate completion program who had completed a
research course taught by the CUNY investigator. Fourteen women participated in
the study; all were accompanied by a female relative or friend. Because of
cultural norms and taboos, paternal attendance in labor settings rarely occurs
and women in labor receive support from mothers, aunts and mothers-in-law. In
summary, accurate estimation of patient pain among nurses and families occurred
less than 25% of the time.
PMID- 11013525
TI - Pain as a mutual experience for patients, nurses and families: a perspective from
New York.
AB - New York was unique among the cities included in this study. The most striking
finding was that the self-described ethnic background of both nurses and patients
was so varied. Many patients and nurses were born elsewhere and were nonnative
speakers. The results cannot be described as cross-countries when so many nations
are represented. Multinational is, perhaps, a more accurate description, but even
that seems inadequate to describe a population as diverse as was this one.
PMID- 11013527
TI - Pain as a mutual experience for patients, nurses and families: a perspective from
Valencia, Spain.
AB - The Spanish data collection was consistent with the overall study design and drew
from three groups: laboring women, children and elderly patients. The Valencia
data was amongst the most detailed, specific and complete in this international
study. This is most likely due to the experienced nature of the Spanish research
team. The study results revealed more commonalities than differences in all age
groups with regard to pain identification and pain alleviation. Across age
groups, pain was identified by study participants through observation and
listening.
PMID- 11013528
TI - Pain as a mutual experience for patients, nurses and families: international and
theoretical perspectives from the four countries.
AB - In Level III, country specific themes, outlined as quantitative and qualitative
findings in Level II, were subjected to extended analyses using the same methods,
from an international perspective. Aggregated themes, examined for patients,
nurses and families, across all four countries are presented in that order.
PMID- 11013529
TI - Controversies in the treatment and management of Lyme disease.
AB - Lyme disease is an infection caused by the bite of the deer tick. It is the most
common vector-transmitted disease in the United States. Past treatment practices
included the administration of oral and/or i.v. antibiotics. Today the question
is "to treat or not to treat." The etiology, signs and symptoms, and current
treatments and management of Lyme disease and its associated somatic complaints
are discussed.
PMID- 11013530
TI - Certification and credentialing to define competency-based practice.
AB - One of the challenges that healthcare organizations face today is how to
effectively establish, document, and evaluate competency in intravenous practice.
The process used to define practice parameters based on national certification
and credentialing versus organizational policies is described. Key attributes,
the role of mentoring, and adverse outcomes are addressed.
PMID- 11013531
TI - Efficacy of ultrasonography in peripheral venous cannulation.
AB - A retrospective study of 431 patients who had peripherally inserted midclavicular
or central catheters placed during a consecutive 13-month period using the
conventional landmark method for placement was compared with a second group of
326 patients, who during a 12-month period had such catheters placed using
ultrasonography. The data demonstrate a 42% decrease in the number of needle
penetrations needed to successfully cannulate veins when ultrasound was used
during placement. There is a 26% greater chance of successful cannulation of the
vein on the first attempt with ultrasound-guided placements than with those using
the traditional landmark method.
PMID- 11013532
TI - Tracking catheters: the care continuum.
AB - Care coordination and development of a plan to track vascular access devices
(VADs) is presented. The article discusses how to establish criteria so that
central venous catheters can be monitored. Specific areas of focus for monitoring
outcomes are reviewed, as is the process of obtaining invaluable information.
This information can be used to support policy and procedure changes and clinical
practice changes to provide quality outcomes.
PMID- 11013533
TI - Cellular effects of cancer chemotherapy administration.
AB - Cancer chemotherapy drugs (CDs) exert a cytotoxic effect by altering one or more
aspects of the growth kinetics of cancer and malignant cells. The pattern and
extent of cytotoxicity determines in part the scientific rationale of various CD
regimens and accounts for many of the common side effects of treatment. This
article provides an overview of the behavior of cancer at the cellular level and
the impact exerted by CDs on normal and malignant cell growth. Examples are
provided of how these scientific concepts affect treatment outcomes and clinical
decisions. The nurse's role in monitoring and managing the related side effects
of treatment also is discussed.
PMID- 11013535
TI - Fitness for practice.
PMID- 11013534
TI - Ethics and total parenteral nutrition: issues for intravenous nurse
professionals.
AB - Healthcare ethics is a hot topic these days. Decisions to withhold or withdraw
various forms of medical therapy are daily events in most hospitals and long-term
care facilities. Intravenous nurse professionals do not need to be bioethicists;
however, they do need to be able to identify problems quickly and know how to
address them. Some of the ethical issues that could be encountered by i.v. nurse
professionals involved in the provision of total parenteral nutritional support
in various clinical settings are examined and explored.
PMID- 11013536
TI - Do new roles contribute to job satisfaction and retention of staff in nursing and
professions allied to medicine?
AB - BACKGROUND: Studies have suggested that job dissatisfaction is a major factor
influencing nurses' and occupational therapists' intention to leave their
profession. It has also been related to turnover of qualified nurses. However,
literature relating to these factors among nurses and professions allied to
medicine in innovative roles is scarce. AIMS: This paper considers the views of
452 nurses and 162 professionals allied to medicine (PAMs) in innovative roles,
on job satisfaction, career development, intention to leave the profession and
factors seen as hindering and enhancing effective working. METHODS: A self
completion questionnaire was developed as part of a larger study exploring new
roles in practice (The ENRiP Study). FINDINGS: Overall there was a high level of
job satisfaction in both groups (nurses and PAMs). Job satisfaction was
significantly related to feeling integrated within the post-holder's own
professional group and with immediate colleagues, feeling that the role had
improved their career prospects, feeling adequately prepared and trained for the
role, and working to protocol. Sixty-eight percent (n = 415) of respondents felt
the role had enhanced their career prospects but over a quarter of respondents (n
= 163; 27%) said they would leave their profession if they could. Low job
satisfaction was significantly related to intention to leave the profession.
CONCLUSIONS: The vast majority of post-holders in innovative roles felt that the
role provided them with a sense of job satisfaction. However, it is essential
that the post-holders feel adequately prepared to carry out the role and that the
boundaries of their practice are well defined. Career progression and
professional integration both being associated with job satisfaction.
PMID- 11013537
TI - The nurse executive: challenges for the 21st century.
AB - AIM: The aim of this paper is to examine the challenges facing the nurse
executive in the 21st century by questioning the traditional attributions of
leadership to the nurse executive role. BACKGROUND: Historically, the leadership
role in nursing has been assumed by the nurse executive. The predominantly female
character of nursing, however, has ensured that demonstrations of leadership
amongst nurses have been infrequent and compatible with prevailing male-defined
ideologies. Examples of this include career restructuring and educational reforms
in Australia. FINDINGS: This paper found that the apparent lack of leadership in
nursing was able to be traced back to early management theories which categorized
leadership as a function of management. CONCLUSIONS: If nurses are to assume
leadership positions in the health care system of the 21st century, nurse leaders
will have to let go of traditional managerial practices and behaviours. In the
emerging health care system of the new century, nurse executive practices will
focus on achieving change rather than predictability in organizational outcomes.
PMID- 11013538
TI - Can information technology help ward sisters become ward managers?
AB - AIM: This paper describes an evaluation methodology that focuses on management
decisions at the ward level in a hospital. BACKGROUND: Successive governments in
the 1990s have provided considerable funds to introduce decision support systems
for ward management, but few have been evaluated rigorously. This paper reviews
the approaches to systems' evaluation that have been developed. METHODS:
Measuring instruments were designed to define and measure management decisions
and those organizational factors which affect decision making. The resulting
difficulty index was validated in a before-and-after study of ward decision
making. FINDINGS: Changes in decision making, after the implementation of a
decision support system, were found to relate to the identified organizational
factors. CONCLUSION: The evaluation methodology described in this paper showed
that the potential benefits of a computerized management system would not be
realized unless managers, doctors and nurses carried out an organizational review
before implementation and then took joint ownership of the system.
PMID- 11013539
TI - Visual art dialogues with elderly persons: effects on perceived life situation.
AB - AIM: The investigation was aimed towards constructing a visual art programme for
communication with elderly. METHODS: Pictures of works of art were used in a
controlled intervention study. Dialogues were performed with elderly persons (age
82.6 years) at a senior's apartment building. The Wheel Questionnaire parameters
structure, motivation, and emotional investment were analysed using ANOVA (mixed
model). FINDINGS: Significant improvement was found in the visual art group (n =
20) compared with a matched control group (n = 20) over the studied period of
time. Communication directions were different in the intervention group compared
with the control group. In the intervention group there was an inexhaustible
source of topics to be discussed that originated from pictures of works of art.
In the control group the dialogues dealt with daily events in the elderly
persons' lives. During the final phase of the intervention period it was
difficult to find topics of conversation in the control group compared with the
intervention group. CONCLUSIONS: The visual art programme is an example of how
the language of works of art could be used for nursing management. The findings
show a new way to care for elderly persons that builds upon elderly persons'
knowledge and personal experience.
PMID- 11013540
TI - Direct care staff's need for support in their perceived work role in day
activities units.
AB - AIMS: This study sets out to investigate direct care staff's views of their need
for support, supervision, and training in their practice in day care settings
when supporting daily occupations among developmentally disabled persons.
BACKGROUND: The first line staff are considered as having a prominent role in the
successful delivery of service. METHODS: Three municipalities, one urban and two
rural areas in southern Sweden, were chosen for the study. The studied population
n = 81 consisted of 94.1% of all staff employed in day activities units
supporting the clients' daily occupations or community-integrated, sheltered work
employment. The data were collected by means of a questionnaire. FINDINGS: This
material identified the staff's perceived work role, and their needs for support,
supervision, and training in the areas of communication, environment adaptation,
individual activation and training methods, with regard to learning disabilities
and special needs. CONCLUSIONS: Care managers should focus upon preparation of
staff support programmes to improve the quality and efficiency in this area of
care.
PMID- 11013541
TI - Is access to a standardized neonatal intensive care possible?
AB - AIMS: This paper aims to determine the factors which impact on the issue of
availability and access to a standard quality of neonatal intensive care
provision in order to clarify strategies for change. BACKGROUND: New targets set
within the NHS reforms have highlighted quality and fair access to services.
Current frameworks for the provision of neonatal services may not be in place to
support a standardized quality service provision. METHODS: The paper examines the
historical and political basis for current models of service, giving a grounding
for recommendations for change in an attempt to achieve a more standardized,
equitable level of care. FINDINGS: Changes within health care policy in the late
1980s and 1990s have led to confusion within the service and a lack of the
definition needed to provide universally accepted criteria on which to base a
regional service provision. CONCLUSION: The organization of services will need to
be reviewed to include the introduction of national and regional data collection
and analysis, and national definitions standardizing service criteria to be used
to support variations in regional models of care. In conjunction with these
recommendations independent auditing processes must exist to allow for
accreditation of services.
PMID- 11013542
TI - Communication: the royal pathway to patient-centered medicine.
PMID- 11013543
TI - The enduring and evolving nature of the patient-physician relationship.
AB - Just as the molecular and chemistry oriented sciences were adopted as the 20th
century medical paradigm, incorporation of the patient's perspective into a
relationship-centered medical paradigm has been suggested as appropriate for the
21st century. It is the medical dialogue that provides the fundamental vehicle
through which the paradigmatic battle of perspectives is waged and the
therapeutic relationship is defined. In many regards, the primary challenge to
the field is the development of operationally defined and measurable indicators
of medical communication that will provide a valid representation of the
conceptual models of the therapeutic relationship. The purpose of this essay is
to explore the implications of a relationship-centered medical paradigm on the
nature of the patient-physician relationship and its expression in the
communication of routine medical practice. An organizing framework for
distinguishing commonly measured communication elements into conceptually
distinct components is suggested. Application of this framework is illustrated
through an empirical study of communication in primary care practice. The results
of the study demonstrate the usefulness of this approach in linking communication
to models of therapeutic relationships. The importance of medical communication
is further explored in a summary of studies that establish its association to
outcomes and in an overview of future challenges to the field.
PMID- 11013544
TI - Bridging the gap. The separate worlds of evidence-based medicine and patient
centered medicine.
AB - Modern medical care is influenced by two paradigms: 'evidence-based medicine' and
'patient-centered medicine'. In the last decade, both paradigms rapidly gained in
popularity and are now both supposed to affect the process of clinical decision
making during the daily practice of physicians. However, careful analysis shows
that they focus on different aspects of medical care and have, in fact, little in
common. Evidence-based medicine is a rather young concept that entered the
scientific literature in the early 1990s. It has basically a positivistic,
biomedical perspective. Its focus is on offering clinicians the best available
evidence about the most adequate treatment for their patients, considering
medicine merely as a cognitive-rational enterprise. In this approach the
uniqueness of patients, their individual needs and preferences, and their
emotional status are easily neglected as relevant factors in decision-making.
Patient-centered medicine, although not a new phenomenon, has recently attracted
renewed attention. It has basically a humanistic, biopsychosocial perspective,
combining ethical values on 'the ideal physician', with psychotherapeutic
theories on facilitating patients' disclosure of real worries, and negotiation
theories on decision making. It puts a strong focus on patient participation in
clinical decision making by taking into account the patients' perspective, and
tuning medical care to the patients' needs and preferences. However, in this
approach the ideological base is better developed than its evidence base. In
modern medicine both paradigms are highly relevant, but yet seem to belong to
different worlds. The challenge for the near future is to bring these separate
worlds together. The aim of this paper is to give an impulse to this integration.
Developments within both paradigms can benefit from interchanging ideas and
principles from which eventually medical care will benefit. In this process a key
role is foreseen for communication and communication research.
PMID- 11013545
TI - Evidence-based guidelines for teaching patient-centered interviewing.
AB - In a rare study of effectiveness of an interviewing method, we previously
reported a randomized controlled trial demonstrating that training in a step-by
step patient-centered interviewing method improved residents' knowledge,
attitudes, and skills and had a consistently positive effect on trained
residents' patients. For those who wish to use this evidence-based patient
centered method as a template for their own teaching, we describe here for the
first time our training program--and propose that the training can be adapted for
students, physicians, nurse practitioners, physician assistants, and other new
learners as well. Training was skills-oriented and experiential, fostered
positive attitudes towards patient-centered interviewing, and used a learner
centered approach which paid special attention to the teacher-resident
relationship and to the resident's self-awareness. Skills training was guided by
a newly identified patient-centered interviewing method that described the step
by-step use of specific behaviors.
PMID- 11013546
TI - Differences in counseling men and women: family planning in Kenya.
AB - A comparison of family planning sessions with male and female clients in Kenya
found distinct gender differences. Most men came for information, while women
wanted to adopt, continue, or change contraceptive methods. Consultations with
men and couples were more than twice as long as consultations with women. Men
communicated actively (for example, by volunteering extra information, asking
questions, and expressing worries) during 66% of their turns to speak, compared
with 27% for women. Providers offered men more detailed information than women,
asked them fewer questions, issued fewer instructions, and responded more
supportively. These communication patterns may be seen as a reflection of Kenyan
gender roles and men's and women's different reasons for seeking family planning
services. Kenyan providers need to improve the quality of their interactions with
women. They also need to anticipate men's outspokenness and understand the male
agenda if they are to counsel men effectively.
PMID- 11013547
TI - The practice orientations of physicians and patients: the effect of doctor
patient congruence on satisfaction.
AB - This study investigated the extent to which the individual orientations of
physicians and patients and the congruence between them are associated with
patient satisfaction. A survey was mailed to 400 physicians and 1020 of their
patients. All respondents filled out the Patient-Practitioner Orientation Scale,
which measures the roles that doctors and patients believe each should play in
the course of their interaction. Patients also rated their satisfaction with
their doctors. Among patients, we found that females and those who were younger,
more educated, and healthier were significantly more patient-centered. However,
none of these variables were significantly related to satisfaction. Among
physicians, females were more patient-centered, and years in practice was related
to satisfaction and orientation in a non-linear fashion. The congruence data
indicated that patients were highly satisfied when their physicians either had a
matching orientation or were more patient-centered. However, patients whose
doctors were not as patient-centered were significantly less satisfied.
PMID- 11013548
TI - Pharmacists' evaluation of key communication skills in practice.
AB - This paper reports the results of a major research initiative into the
identification of key communication skills in community pharmacist-patient
consultations. It is now widely accepted that the quality of practitioner-patient
communication is fundamental to effective health care. However, an analysis of
the literature pertaining to the communication issues facing health professionals
in general and pharmacists in particular emphasised the need for more empirical
research, to chart what pharmacists themselves deemed to be the nature and range
of skills which contribute to effective communication performance in community
pharmacy practice. The main aim of this research investigation was, therefore, to
identify what constituted effective communicative performance by community
pharmacists. This paper provides full details of the repertoire of skills and sub
skills identified as being the core communicative elements of practice. The
results of this research will have relevance for health professionals and
behavioural scientists, and will also contribute to the assurance of quality
within the field of community pharmacy practice.
PMID- 11013549
TI - Measuring patient-centredness: a comparison of three observation-based
instruments.
AB - The aim of this study was to assess the reliability and validity of three
different observation-based measures of patient-centredness. The three face-valid
instruments were each applied to the same sample of 55 videotaped GP
consultations. Associations were explored with consultation 'input' variables
(e.g. patient and doctor demographic characteristics, patient health status) and
'process' variables (e.g. consultation length). The three measures demonstrated
varying levels of inter-rater reliability. Reliability was proportional to
training requirements. Differences in construct validity of the three measures
were evident and their concurrent validity was relatively low. Researchers must
exercise caution in their choice of measurement method because of differences in
how the concept of 'patient-centredness' is operationalized. Greater conceptual
specificity and simplification are required for meaningful, reliable measurement.
The implications for research, and for assessing the quality of individual
doctors' 'interpersonal' care are discussed.
PMID- 11013550
TI - Decision-making in nephrology: shared decision making?
AB - Shared decision-making is considered an important ideal for physician-patient
interaction. The ideal states that health-related values should be discussed
together. It raises two questions: (a) for which decisions is the ideal of shared
decision-making relevant? (b) Which aspects of treatment should be discussed? The
nephrological practice under consideration in this article answers question (a)
as follows: decisions about the type of dialysis are shared decisions, while
decisions about the moment to start dialysis are medical decisions that should be
taken by nephrologists. This situation can be criticized as important health
related values play a role in decisions about starting dialysis. Question (b) is
answered in the nephrological practice under consideration by discussing at least
all important health-related aspects that raise uncertainty about its worth for a
patient. This approach to question (b) is morally and practically defensible.
PMID- 11013551
TI - Effects of video interaction analysis training on nurse-patient communication in
the care of the elderly.
AB - This paper describes an empirical evaluation of communication skills training for
nurses in elderly care. The training programme was based on Video Interaction
Analysis and aimed to improve nurses' communication skills such that they pay
attention to patients' physical, social and emotional needs and support self care
in elderly people. The effects of the training course were measured in an
experimental and control group. They were rated by independent observers, by
comparing videotapes of nursing encounters before and after training. Forty
nurses participated in 316 videotaped nursing encounters. Multi-level analysis
was used to take into account similarity among same nurse encounters. It was
found that nurses who followed the training programme, provided the patients with
more information about nursing and health topics. They also used more open-ended
questions. In addition, they were rated as more involved, warmer and less
patronizing. Due to limitations in the study design, it could not be demonstrated
that these findings can entirely be ascribed to the training course. Further
research, incorporating a randomized controlled design and larger sample sizes,
is recommended to determine whether the results can be attributed to this
specific type of training.
PMID- 11013552
TI - Patients who present physical symptoms in the absence of physical pathology: a
challenge to existing models of doctor-patient interaction.
AB - Many patients seek physical treatment for physical symptoms in the absence of
physical pathology and incur symptomatic interventions that are ineffective,
costly and iatrogenic. It is therefore important to understand how decisions to
provide physical intervention can arise in consultations in the absence of
physical pathology. Existing models of doctor-patient communication are ill
suited to understanding these consultations. A series of studies has provided the
components of an alternative approach that is based on understanding consultation
from the patients' perspective. Specifically, these studies have delineated:
sources of patients' perception of their authority over doctors; what patients
seek by consulting their doctors; and ways that patients use their authority to
influence doctors to provide what they seek. Patients' authority reflects
primarily their own sensory and infallible knowledge of symptoms. Their influence
derives from descriptions of subjective symptoms and from additional strategies
including descriptions of the psychosocial effects of symptoms, catastrophising
and requesting treatment. This analysis suggests directions for future research
and medical training.
PMID- 11013554
TI - Evaluation of communication training programs in nursing care: a review of the
literature.
AB - An important aspect of nursing care is communication with patients. Nurses' major
communication tasks are not only to inform the patient about his/her disease and
treatment, but also to create a therapeutically effective relationship by
assessing patients' concerns, showing understanding, empathy, and providing
comfort and support. In this review, 14 studies, which focus on the evaluation of
the effects of communication training programs for nurses, have been evaluated.
The selected studies were screened on several independent, process and outcome
variables as described by Francke et al. [8]. In this way not only is the
training program taken into account as a variable which may be responsible for
nurses' behavioural change and for changes in patient outcomes, but also a range
of other variables which can give more nuanced explanations for a training
program's degree of effectiveness. On the whole, the studies reviewed showed
limited or no effects on nurses' skills, on nurses' behavioural changes in
practice, and on patient outcomes. Finally, the majority of the studies had a
weak design. The use of experimental research designs should be pursued in future
studies in order to eliminate the influence of confounding variables.
PMID- 11013553
TI - Doctor-patient communication in different European health care systems: relevance
and performance from the patients' perspective.
AB - Our aim is to investigate differences between European health care systems in the
importance attached by patients to different aspects of doctor-patient
communication and the GPs' performance of these aspects, both being from the
patients' perspective. 3658 patients of 190 GPs in six European countries
(Netherlands, Spain, United Kingdom, Belgium, Germany, Switzerland) completed pre
and post-visit questionnaires about relevance and performance of doctor-patient
communication. Data were analyzed by variance analysis and by multilevel
analysis. In the non-gatekeeping countries, patients considered both biomedical
and psychosocial communication aspects to be more important than the patients in
the gatekeeping countries. Similarly, in the patients' perception, the non
gatekeeping GPs dealt with these aspects more often. Patient characteristics
(gender, age, education, psychosocial problems, bad health, depressive feelings,
GPs' assessment of psychosocial background) showed many relationships. Of the GP
characteristics, only the GPs' psychosocial diagnosis was associated with patient
reported psychosocial relevance and performance. Talking about biomedical issues
was more important for the patients than talking about psychosocial issues,
unless the patients presented psychosocial problems to the GP. Discrepancies
between relevance and performance were apparent, especially with respect to
biomedical aspects. The implications for health policy and for general
practitioners are discussed.
PMID- 11013556
TI - [Nursing advise concerning nutritional intake: selecting food is more than just
feeding].
PMID- 11013555
TI - [Assisting diabetics: nutrition counseling and health advise].
PMID- 11013557
TI - [Enteral feeding: hygiene as the primary rule].
PMID- 11013558
TI - [Health aspects of professional clothing. 1. Textile eczema is not a rarity].
PMID- 11013559
TI - [Wellness and fitness in old age homes: enhancing independence and quality of
life for seniors].
PMID- 11013560
TI - [Staying healthy in everyday working life: stress factors in the nursing
profession and how to avoid them].
PMID- 11013561
TI - [Demands on the nursing project manager: motivation through emotional
intelligence].
PMID- 11013562
TI - [Problem-oriented learning: activating case studies and increasing learning
results].
PMID- 11013563
TI - [Developing emotional competence: improving dealing with patients' emotions].
PMID- 11013564
TI - Are children's nurses fit for the next millennium?
PMID- 11013565
TI - Child growth: "Hall" turned upside down.
PMID- 11013566
TI - Comparison of flow rates of holes versus cross-cut teats for bottle-fed babies.
AB - Under laboratory conditions the flow rates of two types of teat were compared.
The openings of Group A teats were in the form of a cross-cut measuring 1.5 mm in
radius plus a small central hole. Group B teats were pierced with a single hole
of 0.5 mm in diameter. Five teats from each group were tested under atmospheric
pressure conditions simulating the effect of a baby's sucking. The results of
this trial confirms the hypothesis that the style of teat affects the flow rate
and that faster flow rates can be obtained with a cross-cut teat rather than a
single-hole teat. Babies using cross-cut teats may also learn to control flow
rates by changing their sucking style.
PMID- 11013567
TI - Fetal echocardiography and congenital heart disease.
AB - Fetal echocardiography has proved a useful tool for prenatal detection of cardiac
lesions and the diagnosis--and, in some cases, the treatment--of fetal
arrhythmias. It is particularly indicated for mothers from high risk groups.
Management of diagnosed heart disease leads either to termination of pregnancy or
to optimal postnatal care for the baby and the mother.
PMID- 11013568
TI - Nurse practitioner at a GP surgery.
PMID- 11013569
TI - Advising on a thermometer for family use.
AB - Families will find it useful to have a clinical thermometer, but parents should
be taught that children's illnesses can present in a range of different ways and
that a young baby can be ill despite having a normal temperature. For people who
find mercury thermometers difficult to use and read, alternatives are digital,
strip or ear thermometers. Digital thermometers are safe, accurate and very easy
to read. Colour-strip thermometers are placed on the skin and change colour at
certain temperatures. As well as forehead strips there is a newer kind which can
be used under the tongue. Ear thermometers are increasingly popular for young
children, being safe, easy to read and accurate.
PMID- 11013570
TI - Enuresis: sharing new research and practice.
AB - We now understand more about the causes and treatment but must work to overcome
the stigma associated with enuresis. Training for professionals needs to be
standardised. Terminology also needs to be standardised. European research
suggests that the quality of the relationship between professional and child can
affect the outcome of treatment. A range of treatments is possible but the first
step is a clear assessment of the problem and cause. It is important to take
account of the family setting. Never assume incontinence is inevitable for
children with special needs and that nothing can be done. Much can be achieved
with appropriate training programmes.
PMID- 11013571
TI - Nappy rash: let's give mothers more help.
AB - Nappy rash affects most babies at some stage. It can occur at any time during the
nappy-wearing years, but reaches a peak between 7 and 12 months. Nappy rash
causes discomfort to babies and distress to mothers, who often feel guilty and
ill-prepared for this problem. Keeping the nappy area dry is the most important
factor in prevention and treatment. Recommend frequent changes of nappy and
leaving the area uncovered when possible. Thrush is present in many cases of
nappy rash. Keeping the area dry deprives thrush of the opportunity to thrive.
PMID- 11013572
TI - [Old age homes: in the process of reform].
PMID- 11013573
TI - [Violence and mistreatment].
PMID- 11013574
TI - [Patient care procedures in homes for the aged].
PMID- 11013576
TI - [Nursing support in an old age home].
PMID- 11013575
TI - [Nursing counseling in incontinence: a function to be developed].
PMID- 11013577
TI - [Palliative care, delay in France].
PMID- 11013578
TI - Cultural values in health care: questions and answers.
PMID- 11013579
TI - Capital investment financing.
PMID- 11013580
TI - Cultural values in health care: a personal view.
PMID- 11013581
TI - Strategies for nurse managers in the 21st century.
PMID- 11013582
TI - Promoting collaborative practice with culturally diverse populations.
AB - Practicing nurses in multiple health care settings must be prepared to manage a
diverse, multicultural patient population and work collaboratively with co
workers representing different cultural backgrounds. To prepare professional
nurses to practice effectively with our increasingly diverse population,
frontline managers and nursing service administrators must act jointly to
increase their knowledge of cultural diversity, share that knowledge, and combine
forces to promote cultural awareness and sensitivity in practice settings.
PMID- 11013583
TI - Effective use of interpreters in health care: guidelines for nurse managers and
clinicians.
AB - Because of the rapid growth of the non-English-speaking population in the United
States, nurses are increasingly likely to be called on to provide care for
patients whose first language is not English. As a result, nurse managers may
need to make interpreters available to health care providers in a variety of
settings to facilitate effective communication and provide quality care. The
purpose of this article is to present nurse managers and nurse clinicians with
information that will enable them to work effectively with interpreters.
PMID- 11013584
TI - Leadership style for facilitating the integration of culturally appropriate
health care.
AB - The dramatic and rapid changes occurring in health care present many challenges
and opportunities for nurse leaders as they deal with a culturally diverse
society. Leadership style is an important consideration for a health care
environment that promotes culturally appropriate care. This article presents a
theoretical model that consists of management of change, principle-centered
leadership, and transformational leadership, and describes how each of these
concepts can assist in creating an environment that fosters culturally
appropriate health care.
PMID- 11013585
TI - The role of nursing administrators in empowering scholarly productivity among
clinicians.
AB - The authors discuss strategies nursing administrators can use to promote
scholarly productivity among their nursing staff. By incorporating mentoring,
promoting collegial teams, involving nurses in the development of goals for
scholarly activity, promoting professionalism, and modifying assignments to
ensure time for research and writing, nurse executives can significantly enhance
scholarly productivity in their professional nursing staff.
PMID- 11013586
TI - Providing care to a culturally diverse community: a mobile academic nursing
center.
AB - Health care institutions are increasingly collaborating with nursing education
programs to provide quality and cost-effective primary health care services to
the community. Mobile academic nursing centers are emerging as viable alternative
sites for these services because they can provide immediate access to health care
services and circumvent logistical problems in access to care. Although not a new
concept, their development as an integral component of the nursing academic unit
is being reexamined in light of health care reform and nursing's role in this
reformation. Unlike stationary clinics, these "clinics on wheels" provide
multisite access to diverse populations and communities. This article describes
how a mobile academic nurse managed center can provide nurses and students with
opportunities to develop competencies in community-based experiences.
PMID- 11013587
TI - Toward a caring culture in professional nursing.
AB - Nursing is a profession founded on the traditional value of caring. Faced with
rapid and tumultuous change in the health care system, nurses are finding the
environment of practice more stressful and less supportive. The ideal of nursing
as a caring community is at risk because of economic and political forces. The
authors review the impact of managed care and reaffirm the notion of the caring
community in the nursing profession. Specific assessment guidelines and
recommendations for the caring community are set forth for practitioners working
in a variety of organizational settings. Organizational culture is emphasized as
the context for caring practice.
PMID- 11013588
TI - Integrating cultural diversity in patient education.
AB - Diversity among clients in the American health care system is increasing as the
population of the United States changes in composition. Health providers,
educators, and supervisors are in unique positions to enhance patient education
among members of diverse cultures by incorporating cultural research and health
beliefs into patient and staff education. Using a culturally defined framework,
health providers can more holistically assess the client and subsequently plan
culturally appropriate care.
PMID- 11013589
TI - The impact of market-based 'reform' on cultural values in health care.
AB - The many issues managed care poses for providers and health networks are
crystallized in the moral problems occasioned by its shifting of the financial
risks of care from insurer to provider. The issues occasioned by market-based
reform include: the problems presented by clashes between public expectations and
payer restrictions; the corporatization of health service delivery and the
cultural shift from humanitarian endeavor to business enterprise the
depersonalization of treatment as time and money constraints stretch resources,
and the culture rewards efficient "business-like" behavior the underfunding of
care for the poor and uninsured, even as these populations grow the restructuring
of care and reengineering of healthcare roles as the emphasis shifts from quality
of care to conservation of resources rapid mergers of both health plans and
institutional providers with all the inherent turmoil as rules change, services
are eliminated, and support services are minimized to save money the unhealthy
competition inherent in market-based reform that posits profit taking and market
share as the measures of successful performance the undermining of the
professional ethic of advocacy the use of incentives that pander to greed and
self-interest. The costs of sophisticated technologies and the ongoing care of
increasingly fragile patients have pulled many other elements into what
previously were considered "privileged" professional interactions. The fact that
very few citizens indeed could pay out-of-pocket for the treatment and ongoing
care they might need led to social involvement (few people remember that both
widespread health insurance and public programs are relatively recent phenomena-
only about 30 years old). However, whether in tax dollars or insurance premiums,
other people's money is being spent on the patient's care. Clearly, those "other
people" never intended to give either the patient or the professional open-ended
access to their collective pocketbooks. Just what form their involvement ought to
take is being tested as "managed care" attempts to control the costs. What limits
are acceptable to providers?: lower profit margins? quality controls? acceptable
risk levels? To patients?: restricted choice? restricted mobility? restricted
access to high tech? And to the general public?: decreased access to high tech?
higher taxes? underserved populations? Abandonment of the sick or poor? Which
"techniques" are acceptable, and which are not?: risk-sharing with providers?
financial incentives for decision makers? rationing access? imposing behavioral
parameters? The issues posed by market-based managed care cannot be adequately
addressed merely in terms of social resources, nor will answers be found in
subordinating human rights to practical materialism. Negotiating ethical
guidelines for the "safe" handling of such problems to the good of individuals
and of society requires a revitalization of the "old" values: the old commitment
to master craftsmanship and altruism, the old emphasis on patient advocacy and
human rights. However, these old values must be applied with the "new" knowledge
of lifestyle choices (and thus personal responsibility), likely outcomes (and
thus reasonable options), and the limits of success (and thus fair redeployment
of health resources).
PMID- 11013590
TI - [Ethics and rights of hospital users].
PMID- 11013591
TI - [Taking care of patients, a question of ethics and equipment].
PMID- 11013592
TI - [Between resentment and companionship: ethics].
PMID- 11013593
TI - [Ethics of abstention from or stoppage of therapy during resuscitation].
PMID- 11013594
TI - [Questions of ethics concerning the legislation of July 29, 1994, in relation to
bioethics].
PMID- 11013595
TI - [Ethics, public hospitals and administration].
PMID- 11013596
TI - [Hospital management and professional ethics].
PMID- 11013597
TI - [Ethics of AP-HP (Public Assistance--Hospitals of Paris)].
PMID- 11013598
TI - [Pedagogic and ethical relations in the formation of health care teams].
PMID- 11013599
TI - [Function of the nursing team and its ethical responsibility].
PMID- 11013600
TI - [Educational use of the Internet in nursing care].
PMID- 11013602
TI - [An evaluation system for efficient training].
PMID- 11013601
TI - [Analysis of diagnostic reasoning of nursing students].
PMID- 11013603
TI - [Ethics of documentation, ethics of the usage of documentation].
PMID- 11013604
TI - Clinical assessment of the reliability of the examination (CARE).
PMID- 11013605
TI - Prediction of risk for patients with unstable angina.
PMID- 11013606
TI - [Carcinoma of the stomach. Role of imaging for primary diagnosis and preoperative
tumor staging].
AB - The aim of imaging of gastric carcinoma has to be to diagnose the carcinoma as
early as possible and to sort out the tumors that are resectable. At the same
time imaging of gastric carcinoma should reduce the number of futile laparotomies
in patients with advanced, non-resectable tumors to a minimum. Today, endoscopy
is the method of choice to diagnose gastric carcinoma. Endosonography is
advantageous if small carcinomas have to be judged for depth of tumor
infiltration (early gastric carcinoma vs. advanced gastric carcinoma) because
high resolution images of the gastric wall are obtained. Staging of large
carcinomas that have grown beyond the gastric wall is best performed by hydro-CT
because CT scans most accurately delineate infiltrations of surrounding
organs/structures and help to plan surgery. Nowadays MRI is not suited for
gastric imaging. MRI, however, has the highest potential to fundamentally improve
staging of gastric carcinoma if high resolution imaging of the gastric wall is
combined with screening for metastases in one examination.
PMID- 11013608
TI - [Magnetic resonance imaging of hemorrhagic transformation in ischemic posterior
infarction].
AB - PURPOSE: To describe the incidence, time course, and clinical correlates of
hemorrhagic transformation (HT) of ischemic stroke in the posterior cerebral
artery territory. METHODS: Within 42 months 48 patients with 52 occipital lobe
infarctions were examined by T1- and T2-weighted MR imaging. The extent and
distribution of secondary hemorrhage were analysed at different intervals after
stroke. Volume of ischemic and hemorrhagic infarction was measured
planimetrically. RESULTS: HT was observed in 71% of the infarcts between the 5th
day and up to 1 year after stroke. HT was most frequently (88%) observed in the
2nd and 3rd month. HT was present in 55% of small infarcts (< 10 cm3), in 88% of
medium size (10-50 cm3), and in all large (> 50 cm3) infarcts. In 92% HT
presented with petechial bleedings within the cortex (64%) or less frequently
(28%) in subcortical structures. The latter types of HT showed no progression and
did not increase the clinical deficits. Space-occupying bleedings occurred in
only two large defects. CONCLUSIONS: In ischemic posterior infarction, HT can
frequently be detected within the first three months after stroke and is
predominantly of the petechial type and seems not to be relevant with regard to
clinical deficits.
PMID- 11013607
TI - [Whole-body MRA on a rolling table platform (AngioSURF)].
AB - PURPOSE: Development of a technique for whole-body MR angiography based on a
rolling table platform and integration of a surface coil. MATERIAL AND METHODS:
The developed rolling table platform AngioSURF (System for Unlimited Rolling
Field-of-view) with integrated surface coil can be mounted on top of the original
patient table of a Siemens Symphony System. Data acquisition was performed with a
standard body array surface coil. The system was tested on three volunteers and
one patient with angiographically documented vascular pathology. Data acquisition
was performed with a 3D-FLASH-sequence (TR/TE 2.1/0.7 ms, flip angle: 20 degrees,
FOV 40 x 40 cm, 80 partitions, matrix 512 x 420 with zero interpolation). Five
data sets were collected in immediate succession during continuous injection of a
paramagnetic contrast agent. Time of acquisition per data set was 10 seconds.
Table repositioning was performed manually within 3 seconds. Thus the total
acquisition time amounted to 72 seconds. RESULTS: No problems with handling
occurred in any of the four cases. The excellent image quality enables detailed
assessment of the displayed vascular territories. CONCLUSIONS: The rolling table
platform with integrated surface coil (AngioSURF) allows diagnostic display of
the arterial vascular system from supraaortic vessels to the distal trifurcation
arteries in only 72 seconds.
PMID- 11013609
TI - [MRI of the prostate after combined radiotherapy (afterloading and percutaneous):
histopathologic correlation].
AB - AIM: To identify the MRI changes of the prostate after combined (high-dose rate
interstitial with external beam) radiotherapy for, localized prostate cancer and
to correlate the findings with histology in order to determine the value of MR
imaging in the follow-up of these patients. MATERIAL AND METHODS: Twenty-three
patients underwent MR imaging at 1.5 T between 6 and 24 months after completion
of combined radiotherapy. The prostate was imaged with axial and coronal T2
weighted sequences and axial T1-weighted sequences before and after intravenous
administration of Gd-DTPA. Quadrant or sextant biopsy was performed in all cases
and three patients with proven persistence of the tumor underwent salvage
prostatectomy. The MRI findings were compared with the biopsy results or the
large-area sections. RESULTS: On T2-weighted images the fibrotically changed
peripheral zone was hypointense while persistent tumor tissue showed
hyperintensity. Solid tumors were depicted when they had a diameter of 1 cm or
more. Persistent tumors of the diffuse multifocal type escaped detection.
Contrast-enhanced T1-weighted imaging yielded no additional information. The
accuracy in detecting persistent tumor was 74%. CONCLUSIONS: Histopathologic
changes seen after combined radiotherapy correlate with the findings on T2
weighted MR images. MR imaging cannot replace follow-up by routine biopsy. Its
only role is assessing local operability in cases found to have increasing PSA
levels during follow-up. Further studies are needed to determine the role of MR
imaging in this patient population.
PMID- 11013610
TI - [Indirect MR arthrography in the diagnosis of rotator cuff lesions].
AB - PURPOSE: To determine the value of indirect MR arthrography in lesions of the
rotator cuff, prospectively versus arthroscopy. METHODS: 63 patients with
suspected shoulder pathology were examined: oblique-coronary and axial T1w
sequences, axial FLASH-2D sequences, furthermore oblique-coronary T2- and PD
weighted sequences were taken. After intravenous administration of 0.1 mmol Gd
DTPA/kilogram body weight and active motion of the shoulder T1w sequences were
repeated. Signal intensities (SI) inside the tendon were quantitatively measured
by the ROI technique (region-of-interest) and the percentual contrast-enhancement
CE was calculated. In 32 patients the results were confirmed by surgical follow
up. RESULTS: The mean SI measured in the supraspinous tendon were higher in
lesions (degeneration, impingement, partial and total rupture), before as well as
after contrast medium, compared to intact findings (p < 0.05). Similarly the
percentual CE (p < 0.05) was higher. We detected 9 total ruptures and three
impingements (for both sensitivity before/after Gd-DTPA 100%), furthermore 6
partial ruptures. Of the latter three were false positive and one false negative,
leading to a sensitivity of 75% and a specificity of 50%. CONCLUSION: The
visualization of rotator cuff lesions can be optimized with indirect MR
arthrography. The detection of partial ruptures remains faulty, because the exact
demarcation of degenerative change and partial rupture is still difficult.
PMID- 11013612
TI - [Multislice spiral CT of the paranasal sinuses: first experiences using various
parameters of radiation dosage].
AB - PURPOSE: To evaluate the potential of multislice CT in the diagnosis of the
paranasal sinuses. METHODS: Dose measurements were performed exposing an Alderson
Rando phantom in a four-slice spiral CT (MS-CT) while applying a variety of scan
parameters. Additionally, 30 consecutive patients underwent a transversal
examination by the MS-CT using 1/1/3.5/0.5 mm spiral parameters and an additional
transversal or coronal scan on a conventional single slice spiral CT (SS-CT) with
2/3/1 mm. Coronal reformations of the MS-CT were compared with the primary
coronal SS-CT, or coronal reformations of the transversal SS-CT, respectively,
with regard to image quality and depiction of relevant anatomical details of the
region. RESULTS: Superficial exposure values at the level of the eye lenses as
well as for the thyroid gland were superior for MS-CT (3.62 mGy, and 0.12 mGy,
resp.) as compared to SS-CT (2.96 mGy, and 0.07 mGy). Image quality was equal or
superior for MS-CT as compared to SS-CT in all but one case. Drawbacks of SS-CT,
such as dental amalgam artifacts, stair step artifacts or partial volume
artifacts did not notably affect the coronal reformations of MS-CT. CONCLUSION:
MS-CT seems to have the potential to replace primary coronal CT of the paranasal
sinuses without any loss of image quality, but may even improve the overall
diagnostic value. Radiation doses may still have to be reduced.
PMID- 11013611
TI - [MRI-guided percutaneous radiofrequency ablation of hepatic neoplasms--first
technical and clinical experiences].
AB - PURPOSE: To evaluate the safety and efficacy of MR-guided radiofrequency ablation
(RFA) of hepatic neoplasms. MATERIAL AND METHODS: 16 hepatic neoplasms (1.3-3.0
cm in diameter) in 11 patients were treated by 22 percutaneous RFA sessions
during a prospective study. 16 G, MR-compatible cooled-tip electrodes with active
lengths of 2 cm and 3 cm, respectively, were placed under MR-guidance in an open
0.2 Tesla MR system (Magnetom Open, Siemens, Erlangen) using fast T1-weighted
sequences. Pretreatment studies, evaluation of tumor necrosis (one week after
last RFA), and further follow-up studies every 3 months were performed using 1.5
Tesla MR systems. RESULTS: The mean procedure time was 2.8 (1.5-3.3) h.
Complications related to percutaneous treatment were not encountered. 14 of 16
neoplasms (87%) showed no CM enhancement during MRI after the last RFA and were
judged to be completely necrotic. In 11 tumors one treatment session was
necessary, in 4 tumors two and in one tumor three. Follow-up studies revealed
persistent complete necrosis in 13 of 14 (93%) tumors during a period of 3-18
(median: 11.8) months. In 5 patients new intrahepatic tumors developed that were
not suitable for further RFA treatment because of their number, size and
location. CONCLUSION: MR-guided RFA using single cooled tip electrodes is safe
and technically effective for treatment of hepatic neoplasms up to 3 cm in size,
however further improvements are necessary.
PMID- 11013613
TI - [Examination of the image quality from digital fluoroscopy equipment with 1k- and
2k-image matrix].
AB - PURPOSE: The image quality of 1k- and 2k-radiographs from digital fluoroscopy
equipments (Sireskop SX and Polystar SX--Siemens) are characterized by comparison
with each other to evaluate the relevance of this technique in clinical routine.
MATERIAL AND METHODS: We examined fabricated and evaluated images with 1k- and 2k
image matrix from several high and low contrast phantoms and from skeleton
phantoms. On the one hand, the digital image values can be used directly for the
evaluation, on the other hand the comparing evaluation by experienced
radiologists resulted from a visual consideration in a blind study. RESULTS: The
quality difference of the 1k- and 2k-images depends mainly on the distance of the
investigated sector of the object to the image intensifier and on the scattering
of the radiation in the object positioned between the investigated sector and the
image intensifier. The nearer the investigated object is located to the
intensifier and the smaller the radiation is scattered in the object, the more
the image quality of a radiograph with a 2k-matrix is increasing in comparison to
an image with 1k-matrix. The higher the tube voltage, the smaller are the
differences. CONCLUSION: The image quality enhancement because of the more
sensitive sampling of the Saticon target in the 2k-matrix is limited by the
opening of the iris positioned in the light distributor. Therefore the image
quality differences of medical 1k- and 2k-radiographs in many cases are small.
PMID- 11013614
TI - [Various forms of rachitis with unusual, malignancy simulating a brown tumor].
PMID- 11013615
TI - [Compression of the suprascapular nerve by a ganglion--MRI diagnosis].
PMID- 11013616
TI - [Posttraumatic dissection of the renal artery--imaging diagnosis and
interventional therapy].
PMID- 11013617
TI - [Stent graft implantation in femoral aneurysms with continuous vascular
ultrasonography].
PMID- 11013618
TI - [On: "Acute heart arrest in spiral CT" by A. Stoger, B. Munsterer and A.
Schinnerl, Innsbruck. in: Fortsch Rontgenstr 2000; 172:490=491].
PMID- 11013619
TI - Trigeminal neuralgia: pathogenesis and treatment.
PMID- 11013620
TI - Subtotal petrosectomy in the treatment of cerebrospinal fluid fistulae of the
lateral skull base.
AB - Cerebrospinal fluid (CSF) fistulae almost invariably lead to meningitis, even in
the absence of other clinically obvious sequelae of the fistula such as a CSF
fluid leak. The only effective means of reducing the risk of meningitis is
surgical closure of the fistula. If surgery is to be recommended to patients with
CSF fistulae even if they are currently asymptomatic, the morbidity of the
procedure must be a principal determinant of the chosen technique. Recovery after
the extracranial approach to a CSF fistula is much more rapid than after an
intracranial procedure. The extracranial route is also free of the long-term risk
of epilepsy which accompanies a craniotomy. The principal disadvantage of the
lateral extracranial approach, failure of treatment, has been largely eliminated
following studies into the obliteration of simple bony cavities using free
adipose grafts. This paper describes our use of the extracranial approach to
closure of CSF fistulae of the lateral skull base.
PMID- 11013621
TI - Meningiomas in childhood and adolescence: a report of 13 cases and review of the
literature.
AB - Meningiomas are relatively uncommon in childhood. They represent 1 to 2% of all
intracranial tumours of infancy and childhood. During the last 30-year period,
from 1964 to 1993, 13 children with a diagnosis of meningioma were operated on at
the Department of Neurosurgery, Hacettepe University School of Medicine. The
meningiomas in the paediatric age group were characterized by multiplicity (23%),
frequent association with neurofibromatosis (23%), intraventricular location
(8%), and the presence of a cystic component in the tumour tissue (23%). These
findings in children differ from those in adults. This study constitutes a
retrospective analysis of these cases and a review of the literature.
PMID- 11013622
TI - Is the technique of posterior transarticular screw fixation suitable for
rheumatoid atlanto-axial subluxation?
AB - The rheumatoid patient with atlanto-axial subluxation presents a major challenge
to the spinal surgeon, owing to the poor wound healing and bone quality.
Traditional wiring techniques are associated with a high complication and failure
rate. Posterior transarticular screw fixation of the atlanto-axial joint offers a
credible alternative and when combined with a Gallie construct offers immediate
true 3-point stability. It is, however, a difficult and demanding technique which
carries a risk of vertebral artery, cranial nerve and spinal cord damage. The
question that arises therefore is "Do the improved stability rates afforded by
this technique really justify the risks of arterial and neurological damage?" To
date there have been no studies of this technique dealing solely with the
rheumatoid patient, with most reports dealing with a heterogeneous patient
population, mainly trauma-related cases. The purpose of this report is to analyse
critically our results with particular reference to the complications that we
have encountered and the technical reasons for their occurrence. We analysed the
clinical and radiological data of 38 rheumatoid patients (six males: 32 females,
mean age of 54 years) with atlanto-axial subluxation who underwent transarticular
screw fixation. Our analysis centred on screw malposition and complications.
Parametric and non parametric statistical analysis was performed. Significance
was accepted at the 5% level (p < 0.05). Our analysis revealed that three
vertebral arteries were damaged. Two of these were recognized at the time of
surgery, with the remaining case only suspected following postoperative CT to
assess screw positioning. Vertebral artery occlusion was subsequently confirmed
by angiography. All three patients were asymptomatic from their arterial injury.
There was only one neurological complication in this series, and this was caused
by a high screw, which damaged the hypoglossal nerve with a temporary nerve palsy
ensuing. Four screws broke, all were made of titanium, but more importantly, all
were also associated with contralateral screw malposition. Stability was achieved
in 95% of cases overall. The high stability rates afforded by this technique do
appear to justify the inherent risks of this procedure. If unilateral screw
fixation only is achieved, we would recommend a period of halo immobilization
until osseous union occurs.
PMID- 11013623
TI - Synovial cysts of the lumbar spine: a review.
AB - Four cases of synovial cyst (ganglion) arising from the facet joints of the
lumbar spine are reported. A typical presenting feature was exacerbation of pain
on standing or walking, mimicking vascular claudication. MRI proved in all four
cases to be the definitive investigation and surgery the treatment of choice,
producing excellent results.
PMID- 11013624
TI - On the usefulness of brain PET scanning to the paediatric neuro-oncologist.
AB - Positron emission tomography (PET) scanning adds a functional dimension to brain
scanning; levels of metabolic activity are imaged and this information may
complement the more "anatomic" imaging of CT and MRI. In a series of 10 young
patients the usefulness of PET scanning technique was investigated. The major
areas of usefulness were the distinction of posttreatment sequelae from active
tumour (both postsurgical MRI changes from tumour and postradiation MRI changes
from tumour) and the localization of persisting tumour amenable to radiosurgical
treatment. The technique was beneficial in assessing continuing activity in
pineal tumours (residual pineal teratoma mass and residual pineocytoma mass) and
in assessing activity in brainstem/cerebellar peduncle gliomas (three cases). In
one unusual case of widespread leptomeningeal melanoma, the PET scan under-read
the situation.
PMID- 11013625
TI - Intraventricular craniopharyngioma: a long-term follow-up of six cases.
AB - Intraventricular craniopharyngiomas are rare tumours. They are wholly within the
third ventricle and can be distinguished from suprasellar lesions which extend
into the third ventricle by the presence of an intact floor of the third
ventricle. They are attached to the wall of the third ventricle to a variable
extent, most commonly in the region of the tuber cinereum. The long-term follow
up on six cases treated by one of the authors is presented. Headache and visual
disturbance were the most common presenting features but, unlike the more common
suprasellar lesions, symptomatic endocrine disturbances were not a common
presenting feature. Total surgical removal can cause hypothalamic damage and the
resulting morbidity can be serious and sometimes life-threatening. Subtotal
removal followed by radiotherapy is probably the treatment of choice for these
lesions.
PMID- 11013626
TI - Treatment of ependymomas. Clinical and non-clinical factors influencing
prognosis: a review.
AB - We review the epidemiological and clinical features of ependymomas as described
in published series as well as the effect on outcome of various treatment
strategies.
PMID- 11013627
TI - Fatal tumoural haemorrhage following decompressive craniectomy: a report of three
cases.
AB - Three cases of large and deep seated anaplastic cerebral glioma were treated by
bone and dural decompression. The patients worsened suddenly within 12 h of
surgery and later died. Postmortem examination revealed a large intratumoural
clot in each case. The effects of decompression and the probable causes of fatal
bleeding are analysed in this report.
PMID- 11013628
TI - Use of the Gigli saw in performing a mid-frontobasal or pterional craniotomy.
AB - The use of the Gigli saw to deal with the inner bony ridges encountered in a mid
frontobasal or pterional craniotomy is presented. Despite the fact that power
driven craniotomes have certain advantages, the authors favour the Gigli saw in
this situation.
PMID- 11013629
TI - Free-lying ectopic meningioma within the orbit.
AB - Intraorbital ectopic meningiomas, which in most cases occur along the orbital
wall, are rare. The authors report a 27-year-old woman who suffered from an
intraorbital meningioma lying apart from the optic nerve and having no connection
with the periorbita or any small nerves.
PMID- 11013630
TI - Recurrent self-inflicted craniocerebral injury: case report and review of the
literature.
AB - Self-inflicted craniocerebral injuries have been reported exclusively in mentally
disturbed patients and criminals. We report a 28-year-old man with a severe
mental disorder who initially hammered a nail into his brain and subsequently
repeatedly inserted foreign objects into his brain. The literature is reviewed
and the surgical and psychiatric management discussed.
PMID- 11013631
TI - Case report: inflammatory pseudotumour of the spine, with literature review.
AB - A case of inflammatory pseudotumour of the thoracic spine is reported. There
appears to be only one previous report of a spinal case. The patient, a 58-year
old woman, presented with symptoms and signs of spinal cord compression
indistinguishable from those due to extradural tumour. The radiological,
operative and pathological findings are presented together with a literature
review.
PMID- 11013633
TI - Supratentorial haemangioblastoma: appearances on MR imaging.
AB - Haemangioblastoma is a rare, benign tumour of vascular origin which usually
occurs in the posterior fossa. Supratentorial haemangioblastomas are
exceptionally rare. In this report we present three cases of supratentorial
haemangioblastoma with MRI findings.
PMID- 11013632
TI - Acute bilateral extradural haematoma of the posterior cranial fossa.
AB - Traumatic haematomas located in the posterior fossa are less frequent than those
above the tentorium. Extradural haematomas are the most common type of haematomas
in the posterior fossa and are usually unilateral. We present the case of a
patient with a bilateral extradural haematomas of the posterior fossa and review
eight cases previously reported in the literature.
PMID- 11013634
TI - Bitemporal hemianopia caused by metastatic carcinoma in a patient with Wegener's
granulomatosis: an unexpected finding.
AB - Metastatic lesions in the suprasellar region are extremely rare. The differential
diagnosis of a focal lesion at this site is wide ranging and lesions often have a
similar radiological appearance. We present a woman with known Wegener's
granulomatosis who lost vision while on medical treatment for a presumed
granuloma at this site. Exploration revealed a metastatic carcinoma of unknown
origin. Attention is drawn to the importance of making a histological diagnosis
in cases of suprasellar lesions.
PMID- 11013635
TI - Symptomatic hypophyseal granular cell tumour: endocrinological and
clinicopathological analysis.
AB - We report a case of a hypophyseal granular cell tumour (GCT) presenting with
visual failure and hyperprolactinaemia (serum prolactin level, 274 ng/ml; normal,
< 10). Magnetic resonance images demonstrated an intrasellar mass with
anterosuperior extension. As the patient had chronic renal failure (CRF) and
hyperprolactinaemia is frequent in CRF patients, a firm preoperative diagnosis of
prolactinoma could not be made. Transsphenoidal removal of the tumour resulted in
improvement of both vision and serum prolactin. Histopathological analysis of the
surgical specimen revealed GCT. A cell kinetic study, the first such report for
this type of tumour, revealed a relatively high Ki-67 staining index of 3.2%. On
electron microscopy, numerous intracytoplasmic granules with various electron
densities were demonstrated. Moreover, cell-processes extending from the granule
rich cytoplasm contained intracytoplasmic filaments but few granules, suggesting
that the filament-rich cells, which are occasionally seen in GCT tissues, are
essentially identical to the granule-rich cells in origin.
PMID- 11013636
TI - Primary intracranial extradural hydatid cyst extending above and below the
tentorium.
PMID- 11013637
TI - Stereotactic radiotherapy for arteriovenous malformations.
PMID- 11013638
TI - Trepan and trephine.
PMID- 11013639
TI - Medicine under socialism: reflections on neurosurgery in the Ukraine.
PMID- 11013640
TI - The intensive care of severe head injury: a survey of non-neurosurgical centres
in the United Kingdom.
AB - Few data exist regarding the management of severe head injury in non
neurosurgical centres within the UK. We aimed to discover the number of intensive
care units admitting head injury patients, the number of patients admitted
annually, and the monitoring and treatment methods followed. Questionnaires were
sent to the senior nurse and consultant in 263 intensive care units within non
neurosurgical hospitals. The response rate was 78.8%, with at least one response
received from 93.2% of hospitals. The severely head injured were routinely
admitted in 56.7% of units. Approximately 2100 patients are admitted annually, a
mean of 15 per unit. Intracranial pressure monitoring is routine in only 9% of
units and 7% are without 24-h facilities for CT, a cause for concern. More
encouragingly, 63% of hospitals have access to rehabilitation facilities.
Distribution of guidelines to all intensive care units participating in the care
of head injury may improve management and outcome.
PMID- 11013641
TI - Brain abscess and hereditary haemorrhagic telangiectasia: a report of three
cases.
AB - Hereditary haemorrhagic telangiectasis (HHT) has long been viewed as a rare
disease which is not usually associated with high morbidity and mortality. We
report three patients with HHT who developed cerebral abscesses secondary to
pulmonary arteriovenous malformations (PAVM).
PMID- 11013642
TI - Dynamic MRI of cerebrospinal fluid flow in endoscopic percutaneous
ventriculostomy.
AB - Endoscopic percutaneous ventriculostomy (EPV) is a new technique to restore the
flow of the cerebrospinal fluid (CSF) to the basal cistern in patients with non
communicating hydrocephalus (NCH). Cardiac gated MRI techniques have been applied
to demonstrate normal and abnormal CSF flow in humans. The aim of this study was
to evaluate the ability of a new multislice spin echo dynamic MRI technique and
amplitude and phase reconstruction to demonstrate the impairment of CSF flow
through the aqueduct preoperatively and to assess the patency of the
ventriculostomy after surgery. Thirteen patients with NCH were studied with
dynamic MRI before and after EPV using multiple sagittal multislice gated SE
acquisitions to demonstrate the CSF flow. Nine patients were clinically improved
by EPS, two remained unchanged and two deteriorated. The permeability of the
ventriculostomy was confirmed in all patients. We think that MRI flow studies are
useful to demonstrate the site of impairment of CSF flow and its aetiology
preoperatively, and to assess the permeability of the ventriculostomy after
surgery in a non invasive way.
PMID- 11013643
TI - Persistent facial pain following microvascular decompression of the trigeminal
nerve.
AB - Pain in the face following microvascular decompression (MVD) can be due to
persisting trigeminal neuralgia (TGN) or a variety of other facial pain
syndromes. If magnetic resonance tomoangiography (MRTA) indicates continuing
vascular compression and the patient has true persistent TGN, then the patient
can be relieved of pain by repeating the MVD. When the MRTA is negative for
continuing compression alternative techniques may be employed; section of the
nerve at the pons may be the treatment of choice for true persistent TGN in the
absence of neurovascular compression. In some cases the pain is dysaesthetic in
nature and not persistent TGN. This is always associated with previous
destructive lesions to the nerve, usually radio-frequency thermocoagulation. When
this component to the pain is recognized pre-operatively the patient must be
warned not to expect relief of this same component of the pain from MVD. When it
is not possible to classify the facial pain clinically, improvement does not
occur following MVD even when there is clear evidence of vascular compression on
MRTA.
PMID- 11013644
TI - Treatment by a specialist surgical neuro-oncologist does not provide any survival
advantage for patients with a malignant glioma.
AB - To determine whether patients with malignant glioma (glioblastoma and anaplastic
astrocytoma) had longer survival times, and lower morbidity and mortality if
operated on by a surgical neuro-oncologist rather than a general neurosurgeon the
outcomes of 236 patients managed within a university surgical neurology
department were analysed. Although both surgical morbidity (8.9 versus 11.8%) and
mortality (3.6 versus 8.8%) were lower following surgery by the specialist neuro
oncologist neither difference was statistically significant. Crude outcome data
suggested patients operated upon by a specialist surgical neuro-oncologist
survived longer (p = 0.067). However, after adjustment for case mix (type of
tumour, year of treatment, MRC prognostic index) using multiple logistic
regression and a hazards model, there was no difference in outcome (p = 0.46, HR
0.884, 95% CI 0.639-1.22). This retrospective study (i) suggests that other
outcome measures are required to validate specialist surgical neuro-oncologist
treatment of patients with malignant glioma; and (ii) confirms the importance of
adjustment for case mix when comparing non-randomized treatment outcomes.
PMID- 11013645
TI - Dynamic CSF flow study in the pathophysiology of syringomyelia associated with
arachnoid cysts of the posterior fossa.
AB - Two patients with posterior fossa arachnoid cysts associated with syringomyelia
are discussed adding to the five cases already reported in the literature. The
formation and progression of syringomyelia secondary to a posterior fossa cyst
and its possible pathophysiology by dynamic CSF flow studies using magnetic
resonance (MR) imaging are discussed and reviewed.
PMID- 11013646
TI - Factors implicated in deaths from subarachnoid haemorrhage: are they avoidable?
AB - The major causes of death following subarachnoid haemorrhage are the effects of
the initial bleed, aneurysmal rebleeding and delayed cerebral ischaemia. Although
in many cases the causes are unavoidable, in others they are potentially
preventable. By conducting a Regional Audit of patients who have died from
subarachnoid haemorrhage, we have attempted to quantify these concerns. The
medical records and CT scans of 200 patients who died from subarachnoid
haemorrhage in hospitals in the East Anglian Region over a 5-year period were
analysed, with particular regard to the identification of potentially avoidable
factors, including radiologically confirmed rebleeding, marked hydrocephalus, and
poor fluid and electrolyte resuscitation. Thirty-three patients presented with
World Federation of Neurosurgical Societies (WFNS) Grade V with fixed pupils.
These patients were deemed unsalvageable. Of the remainder, 106 were good grade
(WFNS I-III) at initial presentation, 77 (73%) of whom died as a result of
rebleeding (mean 10.4 days post-bleed) indicating delays in transfer and
definitive treatment. Of the 61 poor grade patients (WFNS IV and V with reactive
pupils) marked hydrocephalus occurred in 15 (25%) and poor resuscitation in 37
(61%). These were considered contributing factors to their poor clinical
condition. Rebleeding was the main cause of death in the good grade patients, and
correctable factors were identified which are known to contribute to a poor
clinical condition in poor grade patients. The need for more rapid and active
clinical intervention is indicated.
PMID- 11013647
TI - Seizures following posterior fossa surgery.
AB - A retrospective analysis of seizure incidence in 511 patients who underwent
posterior possa operations via a suboccipital craniectomy with prophylactic
anticonvulsant agents, was performed. Thirty patients (5.9%) experienced seizures
within 2 weeks postoperatively. Their mean age was 15 years. Twenty patients had
seizures within 3 h of operation; 24 patients had generalized tonic clonic
seizures. Focal motor seizures with secondary generalization and simple focal
motor seizures were recorded in three patients each. The incidence of
postoperative seizures was highest in patients with acoustic schwanommas (9.09%)
followed by those with medulloblastomas (8.54%) and astrocytomas (8.33%). The
sitting position, associated with venous air embolism (VAE) and or
pneumocephalus, was related to the occurrence (p = 0.001) of postoperative
seizures. Seizures occurred in 24 patients out of 250 cases operated on in the
sitting position compared with 3/170 and 3/91 in the prone and lateral positions,
respectively. Intraoperatively significant VAE occurred in 10 out of 30 patients
and postoperative computed tomography revealed pneunocephalus in 20 out of 30
patients. A higher percentage was found in patients with a preoperative
ventriculoperitoneal shunt or intraoperative ventriculostomy (6.5%) than in those
without (5.1%), but the difference was not statistically significant. In
conclusion, seizures after posterior fossa surgery are a significant problem
which is not reflected in the published literature. Our study highlights the
significance of the sitting position in the causation of seizures after posterior
fossa surgery.
PMID- 11013648
TI - A technique for dural repair following retromastoid suboccipital craniectomy.
AB - The authors describe a simple technique used to achieve a water-tight closure of
the dura mater during suboccipital craniectomy.
PMID- 11013649
TI - Paired colloid cysts of the third and lateral ventricles.
AB - We report the case of a man of aged 27 years who presented with obstructive
hydrocephalus caused by a colloid cyst of the third ventricle. He was found to
have an additional and larger colloid cyst lying adjacent to it, but within the
lateral ventricle. The contents of the two cysts were of different consistency.
We have been able to find only one previous report of more than one colloid cyst
occurring in the same patient and none where one of the cysts lay within the
lateral ventricle.
PMID- 11013650
TI - Chronic encapsulated intracerebral haematoma in a patient with medically
intractable epilepsy.
AB - A patient with a chronic encapsulated intracerebral haematoma presenting with
medically intractable epilepsy is described. A tough capsule containing an old
haematoma was confirmed surgically, and consisted of dense collagenous tissue
with rich neovascularization. The radiological features, aetiology and treatment
of this rare occurrence are discussed.
PMID- 11013651
TI - Giant cephalhaematoma in a 17-year-old boy with Ehlers-Danlos syndrome.
AB - We report a case of giant cephalhaematoma in a 17-year-old boy with Ehlers-Danlos
syndrome. This haematoma occurred after a minor head injury. It increased in
size, immediately after needle aspiration and was responsible for considerable
blood loss. Possible physiopathological mechanisms and treatment modalities are
discussed.
PMID- 11013652
TI - Intraventricular and leptomeningeal dissemination of a pilocytic cerebellar
astrocytoma in a child with a ventriculoperitoneal shunt: case report.
AB - Dissemination of a pilocytic cerebellar astrocytoma is a very rare occurrence. So
far only eight cases have been reported in the literature and in only one of
these cases had the tumour spread into the ventricles. We report a case of a
child who presented with communicating hydrocephalus and a small cerebellar
lesion. The patient was initially treated by a ventriculoperitoneal (VP) shunt
and the lesion was followed-up. Two years later, intraventricular and
leptomeningeal dissemination of the tumour which proved to be a pilocytic
astrocytoma was documented. The role of the VP shunt in diverting metastasizing
tumour cells into the ventricles is discussed.
PMID- 11013653
TI - Low grade pilocytic astrocytoma presenting as a spontaneous intracerebral
haemorrhage in a child.
AB - A girl aged 13 years presented with spontaneous intracerebral haemorrhage.
Initially, no cause could be found but she was later found to have a low grade
pilocytic astrocytoma. This very uncommon presentation was not considered before
surgery.
PMID- 11013654
TI - Very late cerebral metastasis from malignant melanoma.
AB - The appearance of cerebral metastases of malignant melanoma (MM) more than 10
years after the primary diagnosis is extremely rare. We report the case of a
patient with a solitary brain metastasis of MM who came to our observation 11
years after the treatment of the cutaneous lesion. This patient, who up until
then had appeared disease free, presented with two episodes of intracranial
haemorrhage in a 5-month period. Neuroradiological findings (CT, MRI, angiogram)
did not suggest a brain metastasis. The correct diagnosis was reached only after
histopathological examination of the surgically removed lesion. On the basis of
this experience, we stress the importance of a long-term clinical and
radiological follow-up of all patients with MM.
PMID- 11013655
TI - Spontaneous CSF rhinorrhoea due to temporosphenoidal encephalocele.
AB - A 54-year-old woman was referred with spontaneous cerebrospinal fluid (CSF)
rhinorrhoea. CT cisternography revealed a defect in the lateral wall of the left
sphenoid sinus, with an anteromedial temperosphenoidal encephalocele associated
with contrast leakage into the sinus. Subsequent monitoring showed raised
intracranial pressure. Transcranial intradural repair of the encephalocele
followed by lumboperitoneal shunt for the high pressure abolished the leakage of
cerebrospinal fluid.
PMID- 11013656
TI - Neuronavigation: where is the evidence and will there ever be any?
PMID- 11013657
TI - The MEDUNSA sign.
PMID- 11013658
TI - Comment on 'Value of early postoperative plain radiography following BOP fusion
in cervical spinal surgery'.
PMID- 11013659
TI - Multiple primary cerebral hydatid cysts.
PMID- 11013660
TI - Cervical degenerative disease: discectomy or fusion?
PMID- 11013661
TI - A survey of the peri-operative management of patients undergoing anterior
cervical decompression in the UK and Eire.
AB - The peri-operative management of patients undergoing single level anterior
cervical decompression (ACD) in neurosurgical departments in the UK and Eire has
been surveyed. Eighty-eight per cent (132 of 150) of consultant neurosurgeons
responded and of these 118 perform ACD. Nearly all (96%) respondents use
interbody grafts and most of these use autologous bone (63%). A small minority
(4%) never use interbody grafts. Forty-four per cent of surgeons use the same
surgical technique irrespective of the underlying pathology (Cloward 57%: Smith
Robinson 33%; ACD without graft 8%). Surgibone grafts are used by 25% and BOP
grafts by 5%, but 15% of surgeons have abandoned artificial graft materials
because of concerns about non-union. This survey has revealed a diverse range of
practice amongst UK neurosurgeons. A prospective randomized trial is required to
identify whether the theoretical benefits of interbody grafting following
cervical discectomy justify donor site morbidity and the expense and risks of
substitute graft materials.
PMID- 11013662
TI - The costs of managing patients with malignant glioma at a neuro-oncology clinic.
AB - Malignant glioma (glioblastoma and anaplastic astrocytoma) remain incurable
despite extensive resection, radiotherapy, chemotherapy and experimental
therapies. Few studies have addressed either the costs of various treatments for
malignant glioma or their cost effectiveness. The aims of this study were to
identify direct hospital costs of treating patients with biopsy proven malignant
glioma. The study was carried out within the setting of a dedicated neuro
oncology clinic at a university teaching hospital and included 236 patients
treated between 1989 and 1995. The study used the unit costing of each item of
treatment according to NHS National Costing Project. The cost of treatment was
broken down into its various components: bed days, investigations, surgery,
radiotherapy, chemotherapy and neuro-oncology out-patient follow-ups. The mean
costs for each of the items based on 1995 figures for the 157 patients having
surgery followed by radiotherapy were neuroradiological investigations (442
Pounds), neurosurgical bed days (2407 Pounds), neurosurgery (2068 Pounds),
neuropathology (434 Pounds), radiotherapy (8832 Pounds), out-patients (1078
Pounds) and chemotherapy (440 Pounds). Total treatment costs per patient ranged
from 1978 Pounds to 26,980 Pounds. Median costs of care decreased sequentially
with worsening MRC Brain Tumour prognostic group. Management of patients with the
best prognosis (MRC index score of 1-10) cost a median of 16,550 Pounds (range
4572-26,090 Pounds) whilst the median management cost of those in the worst
prognostic group (MRC score 34-38) was 6514 Pounds (range 1978-18,360 Pounds).
The median cost of each week of survival in the patients with the best outcome
(MRC score 1-10) was < 150 Pounds compared to 232 Pounds for each week of
survival for patients in the worst prognostic group (MRC score 34-38). This study
made no attempt to collect costs of supportive or community-based care.
Prospective studies are required to collect such data, as well as assessing the
costs effectiveness of alternative treatment strategies.
PMID- 11013663
TI - Extradural haematoma and diffuse axonal injury in victims of fatal road traffic
accidents.
AB - Seven cases of victims of road traffic accidents with extradural haematoma (EH)
and diffuse axonal injury (DAI) are reported. Such cases are part of a total of
120 victims of fatal road traffic accidents that were subjected to pathological
study. The association of the two lesions occurred in 5.8% of the patients and
all cases of EH were associated with DAI. The latter explains the immediate coma
(absence of lucid interval) and the grave prognosis for all seven patients. It
was noted that EH is relatively infrequent in road traffic accidents, but in such
cases it is more severe since it is frequently associated with DAI and immediate
coma.
PMID- 11013664
TI - The microbial spectrum of brain abscess with special reference to anaerobic
bacteria.
AB - The bacteriological and clinical findings of 18 cases of brain abscess are
presented. Identification and antimicrobial susceptibility of anaerobic strains
was performed both by conventional methods and the newer RapID ANA II panel and E
test methods, respectively. Characterization of the anaerobic isolates was done
by restriction fragment length polymorphism (RFLP). Anaerobic or aerobic
organisms alone were recovered in three (16.6%), and mixed aerobic and anaerobic
in another three (16.6%) patients. There were nine anaerobic isolates. The
predominant anaerobes were Prevotella melaninogenicus (four isolates),
Bacteroides preacutus (three isolates), Fusobacterium nucleatum and
Peptostreptococcus sp. (one isolate each). A total of six aerobic isolates, all
of which were Gram-positive cocci were recovered. All the anaerobic isolates were
susceptible to metronidazole, but two isolates of P. melaninogenicus were
resistant to penicillin. There was complete agreement between the identification
based on biochemical profiles and RFLP patterns. These findings indicate the
microbial complexity of brain abscess and the need to target antimicrobial
therapy against both the aerobic and anaerobic components of infection.
PMID- 11013665
TI - The preoperative skin shave in neurosurgery: is it justified?
AB - Shaving the scalp prior to surgery is a very common practice. Out of 105 cases
operated upon without skin shave at the Royal London Hospital, only one became
infected (0.95%). A search into the history of aseptic surgery shows that there
are no scientific grounds for the practice of shaving. An examination of
contemporary practices worldwide shows that there is a greater realization that
preoperative skin shaving does not confer any benefit against postoperative wound
infection and that, paradoxically, it may lead to higher rates of wound infection
due to the epidermal injury that it inflicts.
PMID- 11013666
TI - Patients with increased intracranial pressure cannot be monitored using near
infrared spectroscopy.
AB - The hypothesis of this study was that with near infrared spectroscopy a decrease
of the regional cerebral saturation would be detectable in patients with
increased intracranial pressure. For this purpose, two study groups were
compared: (A) eight healthy volunteers and (B) eight heart beating organ donors
with brain stem herniation. The regional cerebral saturation was measured
according to the developer's suggestions. Mean arterial pressure and peripheral
pulse oximetry were recorded. The statistical comparison, using the unpaired t
test, revealed no significant differences for the regional cerebral saturation (p
= 0.97) or for the mean arterial pressure or peripheral pulse oximetry between
the groups. In both of the studied situations, no differences in the regional
cerebral situation were detectable, even though the patient situations were
completely antagonistic. Therefore, it is reasonable to discourage the use of the
INVOS 3100 Cerebral Oxymeter to monitor patients with increased intracranial
pressure indirectly.
PMID- 11013667
TI - A preliminary experimental in vivo study of the effect of photodynamic therapy on
human pituitary adenoma implanted in mice.
AB - As surgery alone may prove inadequate to effect a cure for invasive pituitary
adenomas, photodynamic therapy (PDT) was investigated as a possible adjuvant
treatment for this group of tumours. Different subtypes of human pituitary
adenoma cells were implanted subcutaneously into nude mice to study the in vivo
effect of PDT on such lesions. The photosensitizer used in this study was
polyhaematoporphyrin at a dose of 10 mg/kg b.w., followed by light irradiation at
a wavelength of 630 nm with varying light doses between 10 and 75 J/cm2.
Histopathological examination of the treated implants consistently showed tumour
vascular changes with acute inflammatory reaction, interstitial haemorrhage, and
evidence of cell death at higher doses of light. These changes were absent in the
control groups. These findings indicate that the cytotoxic effect of PDT
demonstrated in vitro in previous studies, is also present in vivo.
PMID- 11013668
TI - The pallidotomy debate.
AB - It has been suggested that image-guidance and macro-stimulation alone are not
sufficiently accurate to result in safe and effective lesion localization in
pallidotomy for Parkinson's disease when compared with micro-electrode recording.
This review analyses the data in the series published to date, and compares the
safety and efficacy of the two techniques, finding no evidence to support this
claim. In addition, evidence regarding the necessary accuracy of lesion placement
is reviewed.
PMID- 11013670
TI - Clipping of an aneurysm of a fenestrated basilar artery.
AB - We describe the case of a fenestrated basilar artery aneurysm successfully
clipped by means of a right presigmoid petrosal approach. Three-dimensional CT
angiography enabled the surgeon to plan an approach to an aneurysm in this unique
location, and the presigmoid petrosal approach was suitable for clipping of the
aneurysm.
PMID- 11013669
TI - Brain stem contusion due to tentorial coup injury: case report and
pathomechanical analysis from normal cadavers.
AB - This report is in two parts. First, a case report on a 20-year-old man with a
localized brain stem contusion. Second, in order to elucidate the mechanism of
this injury, an anatomical study was performed. Ten cadaver heads were analysed
to reveal the variations of spatial anatomy around the tentorial incisura. The
lateral tentorial incisura (lateral to brain stem) was situated at the level of
pontomesencephalic junction and nearest to the brain stem along its course. The
shortest distance between them averaged 1.0 mm (0-4 mm). Based on these findings,
primary brain stem injury caused by tentorial incisura occurs at its lateral
portion due to the shortest distance to the brain stem and near the level of
pontomesencephalic junction. In patients with a tentorial incisura closely
related to or touching the brain stem, tentorial coup injury to the brain stem
may occur even with a relatively minor injury. In our case, repeated CT and MRI
proved that the location of contusion was at the pontomesencephalic junction,
coinciding with the level of the tentorial edge. The injury started at the
surface of brain stem. The tentorial edge was close to brain stem in this case.
These radiological findings support the hypothesis that the brain stem contusion
was caused by a tentorial coup injury.
PMID- 11013671
TI - Craniofacial fibrous dysplasia complicated by acute, reversible visual loss:
report of two cases.
AB - We report two cases of craniofacial fibrous dysplasia which presented with acute
visual loss. The first patient had a sphenoid sinus mucocele compressing the
optic chiasm. In the second patient the optic canal was narrowed by dysplastic
bone. In both cases optic nerve decompression restored vision to normal.
PMID- 11013672
TI - Adynamic ileus complicating lumbar laminectomy: a report of two cases.
AB - Adynamic ileus is a well recognized complication of spinal injuries and disease.
We report two cases of adynamic ileus affecting both small and large bowel
following uncomplicated L4/5 laminectomy. Both patients recovered with
conservative treatment, but their hospital stay was prolonged. We have found
three other cases in the literature of ileus affecting only the colon following
laminectomy at this same level.
PMID- 11013673
TI - Primary cranial Ewing's sarcoma.
AB - Primary Ewing's sarcoma of the cranium is extremely rare, with only 17 cases
reported so far. We describe a further case with involvement of the
frontotemporal region and the orbit. The patient, an adult male, was admitted
with headache and papilloedema, and later developed localised swelling and
proptosis. He was treated with surgery, radiotherapy and chemotherapy, and was
free from metastases during a follow-up of 14 months. The prognosis of Ewing's
sarcoma is improving with radiotherapy and chemotherapy. Further cases are needed
to study the biological behaviour of primary cranial Ewing's sarcoma.
PMID- 11013674
TI - Brain abscess as the presenting feature of melioidosis.
AB - Central nervous system involvement in melioidosis is rare and there are only a
few reports of the causative organism, Burkholderia pseudomallei, causing a brain
abscess. We report a patient who presented to us with a brain abscess due to this
organism and emphasize the need for a high degree of suspicion for this disease
in tropical countries and treatment with the appropriate antibiotics, as the
mortality associated with this disease is very high.
PMID- 11013675
TI - Anterior skull base osteoid osteoma: case report.
AB - Osteoid osteoma is a benign bone tumour which rarely occurs in the skull. A case
of such a tumour in the posterior ethmoid region bulging into the anterior
cranial fossa is reported in a 42-year-old woman who presented with intense
frontal headaches. Excision of the tumour was performed through a subfrontal
approach.
PMID- 11013676
TI - Unilateral proptosis and chemosis caused by dural arteriovenous malformation of
the superior sagittal sinus.
AB - We describe a patient with unilateral proptosis and chemosis resulting from a
dural arteriovenous malformation (AVM) of the superior sagittal sinus (SSS) fed
mainly by branches of both external carotid arteries. The symptoms may have been
caused by increased SSS pressure and disturbance of venous flow by the dural AVM.
PMID- 11013677
TI - Primary spinal melanoma: case report.
AB - We report a case of primary melanoma of the thoracic spinal cord revealed by
progressive bilateral lower extremity weakness associated with sensory loss and
urinary dysfunction. The preoperative MRI revealed an intramedullary tumour from
T7 to T9. Treatment was by complete surgical excision without radiotherapy.
Histopathology and immuno-histochemical studies confirmed the diagnosis. The
postoperative course was satisfactory with no sign of recurrence after 28 months
of postsurgical follow-up. Primary spinal melanomas are rare intramedullary
tumours that can be cured by appropriate surgical treatment.
PMID- 11013678
TI - Trochlear nerve neurinoma.
PMID- 11013679
TI - Medical editors trial amnesty (META)
PMID- 11013680
TI - Sir Geoffrey Jefferson 1886-1961.
PMID- 11013681
TI - Distal anterior cerebral artery aneurysms: a clinical series.
AB - Thirty patients with distal anterior cerebral artery (DACA) aneurysms were seen
at the Royal Adelaide Hospital in the period 1970-1996. There were seven males
(23%) and twenty three females (77%) with a mean age of 50 years. The average
follow up was 5 years. Multiple aneurysms were present in seven cases (23%). The
mean size of aneurysms was 5 mm. There were two post-traumatic aneurysms and one
mycotic aneurysm. Out of the 30 cases, 19 presented with subarachnoid haemorrhage
from ruptured DACA aneurysms. Eight (42%) of them were in good clinical grade (I
or II). Operations were carried out in 25 (83%) patients. All five cases with
unruptured aneurysms and the eight patients with good clinical grade had good
recovery. In contrast, only six (55%) out of 11 patients with poor clinical grade
had good outcome. The overall management mortality for the 19 cases with ruptured
aneurysms was 16%. Postoperative complication occurred in two cases (8%), one
patient developed deep vein thrombosis and seizures, the other patient had
transient upper limb weakness. Although there is a definite trend towards better
management outcome in the published series of DACA aneurysms over the years,
there is still significant mortality and morbidity in the poor grade patients.
Early surgery will prevent the deaths from rebleeding and may allow optimal
management of vasospasm.
PMID- 11013682
TI - Histopathological changes following the use of biological and synthetic glue for
dural grafts: an experimental study.
AB - Dural defects and CSF leaks are common neurosurgical problems and the search for
a suitable sealant continues. The effects of such sealants on meninges and brain
have not been previously studied. To study the effect of two commonly used
sealants, burrholes were made in 20 rats, with the creation of dural tears which
were covered with human cadaveric dura smeared with synthetic (cyanoacrylate)
glue and gelatine (GRG) glue. Plain dura, placed in one of the burrholes served
as a control. An intense inflammatory reaction was observed with both glues,
which was found to persist till the eleventh week.
PMID- 11013684
TI - A clinical evaluation of the Codman MicroSensor for intracranial pressure
monitoring.
AB - The strain-gauge Codman MicroSensor intracranial pressure (ICP) transducer has
shown consistently good laboratory performance. To assess the practical
performance of the system in patients following acute brain injury, 10 patients
were fitted with a MicroSensor and a second ICP monitor. In five cases this was a
fibre-optic transducer and in five cases an intraventricular fluid-filled device.
Paired ICP values were recorded every 5 min. ICP values ranged from 0 to 31 mmHg.
Altman-Bland plots showed that individual readings could differ by as much as 9
mmHg. Further analysis showed that much of this disagreement could be explained
by a constant offset on each occasion. Comparison traces of ICP in individual
patients show high agreement in timing and size of changes. The unexplained
constant offset leads to uncertainty about the true ICP. Treatment decisions are
often based upon absolute levels of ICP and patient care may therefore differ
depending upon the monitor used.
PMID- 11013683
TI - Chemotherapy for aggressive or anaplastic high grade oligodendrogliomas and
oligoastrocytomas: better than a salvage treatment.
AB - This series reports a pilot study of chemotherapy conducted for newly diagnosed
and relapsing patients with oligodendrogliomas and oligoastrocytomas. Twenty
three patients with clinically or histologically aggressive tumours were eligible
to receive procarbazine CCNU and vincristine (PCV) chemotherapy followed by
radiotherapy in previously non irradiated patients. Sixteen (69%) responded to
chemotherapy with complete responses in two patients and partial responses in 14.
Previously irradiated patients were as likely to respond to PCV as those
previously non irradiated. An over 1-year history of seizures was the main
clinical prognostic factor of response. All toxicities were manageable and no
treatment related deaths occurred. Chemotherapy is an effective treatment in
aggressive oligodendrogliomas. Further studies must assess the role of
chemotherapy in the multidisciplinary management of oligodendroglioma.
PMID- 11013685
TI - Benign tumours of the pineal region: a prospective study from 1983 to 1997.
AB - Tumours of the pineal region are rare. Between 1983 and 1997, 128 patients with
pineal masses were treated in our institution. Forty-eight (38%) of these were
benign. There were 13 patients with meningiomas, 11 with epidermoid tumours, 10
with cystic lesions, five with vascular lesions, five with infective pathology
and four with mature teratomas. All patients were managed surgically. Ventriculo
peritoneal shunts were inserted preoperatively to relieve hydrocephalus. Open
surgery thereafter was mostly done through the supracerebellar infratentorial
approach. The occipital transtentorial route was preferred for meningiomas.
Stereotactic biopsy was used in two patients only. Radical excision of tumours
was achieved in 55% of operated cases, partial excision in 25%. Radiation
therapy, which was the mainstay of treatment earlier, was used only in two
patients. Stereotactic radiosurgery was used in one patient. All patients
followed up were found to be in good or excellent condition.
PMID- 11013686
TI - A study on the efficacy of intraventricular urokinase in the treatment of
intraventricular haemorrhage.
AB - Twenty-one patients with intraventricular haemorrhage were randomized to two
treatment groups. Both groups had bilateral external ventricular drains inserted,
but only the treatment group received 50,000 IU urokinase instilled into the
ventricles. The clinical and radiological progress, and 1- and 6-month outcomes
were compared. The group that received urokinase treatment was shown to have an
improved outcome, with a lower mortality and a lower incidence of hydrocephalus
requiring shunt insertion. No haemorrhagic complications were seen in either
group, although the treatment group had a slightly increased rate of drain
related ventriculitis.
PMID- 11013687
TI - Gliomatosis cerebri: disconnection of the cortical grey matter, demonstrated on
PET scan.
AB - 18-FDG and 11C methionine PET scans were performed on two patients with
gliomatosis cerebri. The cortical grey matter was hypometabolic when compared
with normal. The findings support the concept that the cerebral cortex becomes
functionally disconnected in this disease owing to the infiltrative nature of the
underlying tumour. This may account for the high incidence of dementia in the
course of this disease. In one of the cases described here, there was clear
evidence of progression from a discrete tumour mass of glioma to gliomatosis
cerebri and this progression argues against the WHO classification of this
disorder separately from glioma.
PMID- 11013688
TI - The role of descending basal ganglia connections to the brain stem in
parkinsonian akinesia.
AB - Akinesia is the most disabling symptom of Parkinson's disease. The neural
mechanisms underlying it probably involve the descending projections of the basal
ganglia to the brain stem as it improves after a pallidotomy or subthalamic
nucleotomy but not after a thalamotomy. We describe the effects of lesioning the
pedunculopontine nucleus in the normal primate in generating an akinetic
syndrome. The possible clinical implications of this study are discussed.
PMID- 11013689
TI - Are there differences in the symptoms, signs and outcome after lumbar disc
surgery in the elderly compared with younger patients?
AB - Age is claimed by several authors to be a predictor of bad outcome after lumbar
disc surgery. The aim of this study is to evaluate the influence of the patients
age on preoperative symptoms and the outcome. General data, symptoms, signs and
neurological findings of 219 patients were recorded preoperatively Ninety-two per
cent of the patients received a follow-up examination by an independent
investigator after a mean of 298 days. All patients older than 59 years were
defined as belonging to the group of elderly patients (n = 30). The other
patients were defined as the younger group (n = 189). The outcome was measured by
a visual analogue rating scale. Outcome was not statistically different in both
groups. In our opinion, the indications for surgery for a lumbar disc herniation
should be no different for older patients even though nerve root tension signs
appear to be less marked in older patients.
PMID- 11013690
TI - Multilayer reconstruction of the anterior cranial fossa floor.
AB - A case is described where a reconstruction of a complex defect in the floor of
anterior cranial fossa was successfully carried out using multiple layers of
vascularised pedicle flaps. The 42-year-old male patient had previously undergone
multiple surgical procedures for persistent cerebrospinal fluid (CSF) rhinorrhoea
following a vehicular accident 16 years previously. The extensive vascular supply
to the layers of the scalp, pericranium, temporalis muscle and its fascial
coverings was exploited in fashioning the flaps.
PMID- 11013691
TI - Neurenteric sinus dorsal to the thoracic spine with an associated cutaneous
haemangioma: case report.
AB - The case of an infant born with a large cutaneous haemangioma overlying the
thoracic spine is presented. A small midline pit lay within the haemangioma,
histological examination of which confirmed it to be a neurenteric sinus. The
possible embryological origins of this rare lesion are discussed.
PMID- 11013692
TI - Primary sphenoid and petrous apex esthesioneuroblastoma: case report.
AB - A 62-year-old woman presented with raised intracranial pressure and features of a
right cerebellopontine angle tumour with extension into the right middle cranial
fossa. The patient died before a surgical excision could be performed. The
autopsy revealed a primary esthesioneuroblastoma of the sphenoid sinus eroding
the petrous bone and extending into the middle cranial fossa with metastatic
tumour in the liver, and paratracheal and hilar lymph nodes. Although rare,
esthesioneuroblastoma must be considered in the differential diagnosis of petrous
sphenoid lesions.
PMID- 11013693
TI - Intramedullary ossified cavernous angioma of the spinal cord: case report.
AB - A case of a heavily ossified cavernous angioma of the spinal cord along with its
histological features and surgical implications is reported. The unusually dense
calcification and even bone formation along with the unique eggshell-like cyst
formation posed problems in diagnosis and surgical excision. This calcified
vascular lesion was treated by subtotal excision.
PMID- 11013694
TI - Posterior fossa arachnoid cyst presenting as high cervical cord compression.
AB - We report a 16-year-old boy who presented with high cervical cord compression
caused by a midline posterior fossa arachnoid cyst lying below the vermis.
Cystoperitoneal shunting resulted in a dramatic improvement of neurological
signs.
PMID- 11013695
TI - Pineal apoplexy: an occurrence with no diagnostic clinicopathological features.
AB - Symptomatic pineal apoplexy unlike pituitary apoplexy is uncommon. A patient with
an apoplectic pineal cyst, identified preoperatively using MRI and confirmed
histologically presented with episodic syncope, and features of raised
intracranial pressure, but no localizing neuro-ophthalmological signs. This case
prompted a review of the clinicopathological features of pineal apoplexy. There
are no diagnostic clinical features and the neuropathological associations of
pineal region haemorrhage are diverse. There is no consistent clinicopathological
syndrome of pineal apoplexy.
PMID- 11013696
TI - Anaplastic ganglioglioma: case report and review of the literature.
AB - A 10-year-old girl underwent radical decompression of a right temporal tumour
extending to the insular cortex which proved to be a differentiated
ganglioglioma. One year later, she presented with a bleeding right frontal tumour
extending to the insula, the histology of which showed it to be the anaplastic
variant of ganglioglioma. She underwent postoperative radiotherapy but died 6
months after the second operation. Anaplastic ganglioglioma is a rare variant of
ganglioglioma and progression of the latter to anaplastic ganglioglioma is an
extremely rare occurrence. The literature regarding ganglioglioma is reviewed.
PMID- 11013697
TI - Multiple cerebellar haemangioblastomas symptomatic during pregnancy.
AB - A patient with von Hippel-Lindau disease presented during her seventh week of
pregnancy with obstructive hydrocephalus and brainstem compression caused by
multiple cerebellar haemangioblastomas. Surgery was performed to relieve the
hydrocephalus and remove the right cerebellar tumour. The patient's subsequent
course supports the hypothesis of vascular engorgement of cerebellar
haemangioblastomas during pregnancy.
PMID- 11013699
TI - Trigeminal neuralgia.
PMID- 11013698
TI - Pituitary tumours: recommendations for service provision and guidelines for
management of patients. Royal College of Physicians.
PMID- 11013700
TI - The role of mebendazole in the surgical treatment of central nervous system
hydatid disease.
PMID- 11013701
TI - [Imaging of conductive hearing loss].
AB - CT study of the middle ear and ossicular chain plays a major role in assessing
the etiology of conductive hearing loss. A normal otoscopic examination is
compatible with a fenestral otosclerosis, a minor ossicular chain aplasia or a
traumatic dislocation of the ossicular chain. Fenestral otosclerosis diagnosis
does not usually require a CT examination except in children without familial
history and mixed hearing loss with a transmissional component. In retraction
pockets and middle ear cholesteatomas CT allows precise location, extension and
defines surgical landmarks. In middle ear tumors CT and MR studies need to be
used in conjunction to differentiate glomus tumor, primary cholesteatoma and
congenital vascular anomalies.
PMID- 11013702
TI - [Imaging of post-traumatic tinnitus, vertigo and deafness].
AB - Tinnitus, hearing loss, and more rarely disequilibrium are common sequela of
temporal bone trauma. Hemotympanum may cause a transient and immediate conductive
hearing loss. HRCT depicts ossicular dislocation (most frequently incus),
producing a long-term conductive hearing loss. Labyrinthine trauma causing
neurosensory hearing loss or/and acute vertigo may be depicted by MRI, showing an
abnormal non-enhancing high signal T1 of the membranous labyrinthine fluid. MRI
also may show low signal T1 and T2 fibrotic areas of the membranous labyrinth,
especially of interest if cochlear implant surgery is planned. Perilymphatic
fistulas are to be searched in case of fluctuant hearing loss. Both HRCT and MRI
may show window damage: filling of the tympanic recess, rupture of the window
membrane, intra-vestibular luxation of the stapes, or occasionally
pneumolabyrinth.
PMID- 11013703
TI - [Polyps and polyposis of the paranasal sinuses].
AB - Discussion is about the different types of naso-sinusal polyps, isolated
inflammatory polyps and some other ambiguous types like inverted papilloma, so
called haemorrhagic polyps, pseudo-polyps and reactional polyps collecting very
heterogeneous and various clinical, CT and evolutive entities.
PMID- 11013704
TI - [Imaging of tumors and pseudotumors of the ear].
AB - CT and MRI are in most of the cases associated in imaging of tumours and pseudo
tumours of the temporal bone. The tumours of the external auditory meatus
particularly the malignant ones are rare. It is of a great interest to delineate
a possible extension to the chorda tympani. Secondary cholesteatoma are the most
frequent pseudo-tumours of the middle ear: CT and MRI evaluate very well their
extension particularly in the giant forms. Others tumours like tuberculosis,
histiocytosis, primitive cholesteatoma, tympanic body++ tumours may be diagnosed
by imaging as well as the neuroma of the facial nerve, the meningioma or some
rarer lesions as the adenoma, or the carcinoid tumour of the middle ear. The
adenoma of the endolymphatic sac is the only true tumour of the membranous
labyrinth whose diagnosis is nicely made by MRI. The primitive cholesteatoma, the
neuroma of the facial nerve may reach the labyrinthine bone and are easily
diagnosed by imaging which generally speaking is very good in evaluating the kind
of pathology of each cavities, delineating the extension of the lesions and
orientating the surgical procedures.
PMID- 11013705
TI - [Imaging of cervical masses].
AB - Imaging plays an essential role in the management of neck disease. It can
identify true disease versus pseudomasses, and it allows to differentiate between
lymph node metastases and other cervical masses. MR imaging and/or CT can show
the exact location and extent of a lesion, and can help to anticipate its nature.
PMID- 11013706
TI - [Radio-anatomy of lymph node groups in the area of otolaryngology].
AB - Imaging plays an essential role in the management of head and neck lymph node.
Knowledge of the anatomy is indispensible to interpret ultrasound, CT, and MR
examination.
PMID- 11013707
TI - First report on the systematic sequencing of the small genome of Encephalitozoon
cuniculi (Protozoa, Microspora): gene organization of a 4.3 kbp region on
chromosome I.
AB - Belonging to a large group of parasitic amitochondrial protozoans (Microspora),
Encephalitozoon cuniculi infects humans and other mammals. Because of its medical
importance and small genome size (2.9 Mbp), we are systematically sequencing its
smallest (217 kbp) chromosome. The shotgun cloning strategy now has produced the
sequence of randomly dispersed contigs representing more than 180 kbp of this
chromosome. The present report describes analysis of the 4.3 kbp contig, which
includes the complete coding regions of dihydrofolate reductase (DHFR),
thymidylate synthase (TS), and serine hydroxymethyl transferase (SHMT) genes and
the partial coding region of an aminopeptidase (AP) gene. In contrast to the
other reported protozoan genes, DHFR and TS are encoded by two different open
reading frames (ORFs). The SHMT gene is the first one identified in a protozoan
and corresponds to the cytosolic form of the enzyme. No introns were detected,
and the intergenic noncoding regions do not exceed 50 bp. The mean GC content is
close to 60%, and there is a G or C third-base codon bias. Transcription and
translation initiation signals also are analyzed, and a model for the mRNA-ssu
rRNA interactions is proposed.
PMID- 11013708
TI - Mapping chicken genes using preferential amplification of specific alleles.
AB - To map the chicken genome, an international reference population was developed at
our laboratory (East Lansing, MI) using an F2 backcross between inbred jungle
fowl (JF) and inbred white leghorns (WL). To augment the number of type I genes
on the East Lansing (E) map, segregation of the JF-specific allele was followed
using preferential amplification of specific alleles (PASA) in polymerase chain
reactions (PCR). Among 15 functional genes that were added to the E map, agrin
and mannose-6-phosphate receptor genes were found to occur in conserved syntenic
groups. Using this PCR-based approach, six conserved groups spanning more than
243 centimorgans (cM) in the chicken were syntenic with human and mouse.
PMID- 11013709
TI - On the presence and organization of open reading frames of the nonmotile pathogen
Brucella abortus similar to class II, III, and IV flagellar genes and to LcrD
virulence superfamily.
AB - Brucellae are pathogenic, nonmotile bacteria that are facultative intracellular
parasites. Little is known about the genetics of these bacteria. Open reading
frames from Brucella abortus with similarity to the flagellin, M-ring, and hook
of related bacteria were discovered. The open reading frames encode proteins of
three of the four flagellum gene classes, namely II, III, and IV. A homolog of
the LcrD virulence superfamily was also found. This superfamily is involved in
type III protein secretion. B. abortus has the potential for motility and type
III secretion.
PMID- 11013710
TI - Eggsacting standards.
PMID- 11013711
TI - Nothing fishy at FDA seafood laboratory.
PMID- 11013712
TI - International round-robin for dioxins and furans.
PMID- 11013713
TI - Embalming in the Old Kingdom of Pharaonic Egypt.
PMID- 11013714
TI - Exploring electrochemical interfaces with solid-state NMR.
PMID- 11013715
TI - Screening and testing for endocrine disrupters.
PMID- 11013716
TI - Isolation of amino acids from natural samples using sublimation.
AB - Amino acids have appreciable vapor pressures above 150 degrees C and will sublime
under partial vacuum at elevated temperatures without any racemization or
decomposition. The recoveries of several amino acids including aspartic acid,
serine, glycine, alanine, alpha-aminoisobutyric acid, and valine were optimized
by varying the temperature and duration of sublimation. Sublimation has been
shown to be a rapid and effective technique for the isolation of amino acids from
natural samples for enantiomeric analyses and a good substitute for conventional
cation-exchange desalting techniques.
PMID- 11013717
TI - Voltammetric and pharmacological characterization of dopamine release from single
exocytotic events at rat pheochromocytoma (PC12) cells.
AB - Although rat pheochromocytoma (PC12) neurotransmitter storage vesicles are known
to contain a variety of neurotransmitters including catecholamines, there is
little evidence that the molecular species detected during amperometric
monitoring of exocytosis is a catecholamine. Rather, as these are catecholamine
containing cells, one assumes catecholamines are released. Additionally, although
the total amount of transmitter released can be quantified, it has been extremely
difficult to evaluate the concentration at the point of release for each
exocytosis event. Interpreting voltammograms obtained in the attoliter volume
affected between the electrode and the cell and defined by the size of the
exocytosis pore during exocytosis is an extreme analytical challenge. Here we use
voltammetry of approximately 10(-19) mol released from individual exocytosis
events to identify, along with pharmacological evidence, the released compound at
PC12 cells as a catecholamine, most likely dopamine. The area of the electrode at
which oxidation occurs following an exocytosis event is proportional to the
temporal delay prior to acquisition of a voltammogram. This model allows
determination of relative concentrations from individual release events and has
been used to examine events at control cells and cells incubated with the
dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA). Exposure to L-DOPA
(100 microM for 1 h) results in 145 detectable events for 11 cells compared to 77
events for 29 control cells, clearly indicating that vesicles can be "loaded"
with dopamine. However, the concentrations measured at the electrode surface
provide similar distributions for both L-DOPA-treated and control cells. Cyclic
voltammetric measurements of relative concentration for zeptomole levels of
transmitter in attoliter volumes provide evidence that loading vesicles by
increased transmitter synthesis does not lead to elevated concentrations at
individual release sites.
PMID- 11013718
TI - Analytical applications of cooperative interactions associated with charge
transfer in cyanometalate electrodes: analysis of sodium and potassium in human
whole blood.
AB - Nickel electrodes chemically modified with an interfacial layer of nickel
ferrocyanide are shown to be of analytical utility for simultaneously sensing
sodium and potassium ions in aqueous solutions, human whole blood serum, and
human whole blood. By controlling the charge-transfer characteristics of this
versatile interface, interfering blood proteins and potential interferences
associated with other alkali cations can be avoided. A solid-state model which
explains the excellent simultaneous selectivity and sensitivity of the nickel
ferricyanide interface is proposed.
PMID- 11013719
TI - Micromethod for the investigation of the interactions between DNA and redox
active molecules.
AB - A novel microscale and surface-based method for the study of the interactions of
DNA with other redox-active molecules using DNA-modified electrodes is described.
The method is simple, convenient, reliable, reagent-saving, and applicable for
DNA studies, especially those involving microsamples. Information such as binding
site size (s, in base pairs), binding constant (K), ratio (K0x/KRed) of the
binding constants for the oxidized and reduced forms of a bound species, binding
free energy (delta Gb), and interaction mode, including changes in the mode of
interaction, and "limiting" ratio K0x0/KRed0 at zero ionic strength can be
obtained using only 3-15 micrograms of DNA samples. The method was developed
using [Co(Phen)3]3+/2+ (Phen = 1,10-phenanthroline)/double-stranded DNA (dsDNA)
modified gold electrodes and [Co(bpy)3]3+/2+ (2,2'-bipyridyl)/dsDNA-modified gold
electrodes as model systems. For the [Co(Phen)3]3+/2+/dsDNA-modified gold
electrode system, a K2+ of (2.5 +/- 0.3) x 10(5) M-1 and an s of 5 bp were
obtained in 5 mM pH 7.1 Tris-HCl buffer solution containing 50 mM NaCl. For
[Co(bpy)3]3+/2+/dsDNA-modified gold electrodes, K3+ and s values of (1.3 +/- 0.3)
x 10(5) M-1 and 3 bp, respectively, were obtained. While the s values are
consistent with those reported in the literature obtained by solution methods,
the K values are almost an order of magnitude larger. A transition in the nature
of the interaction between dsDNA and [Co(Phen)3]3+/2+, from electrostatic to
intercalative with increasing ionic strength, was found in our studies. Negative
values of delta E0' for [Co(bpy)3]3+/2+ bound to dsDNA suggest that its
interaction with dsDNA is predominantly electrostatic over the ionic strength
range of 5-105 mM. The "limiting" ratio K3+0/K2+0 of 22 obtained for
[Co(Phen)3]3+/2+ bound to dsDNA at zero ionic strength suggests that
electrostatic interactions are predominant over intercalative ones under these
limiting conditions. The ratio for [Co(bpy)3]3+/2+ of 16 also indicates that the
3+ form binds to dsDNA more strongly than the 2+ form at zero ionic strength. For
[Co(Phen)3]3+/2+/single-stranded DNA (ssDNA)-modified gold electrodes, the
nonuniformity of the surface structure of ssDNA-modified gold electrodes greatly
complicates the analysis. A system consisting of a dsDNA-modified gold electrode
and [Co(tppz)2]3+/2+ (tppz = tetra-2-pyridyl-1,4-pyrazine) was studied by this
method, with a K2+ value of (5 +/- 1) x 10(5) M-1 and an 8 value of 7 bp being
obtained.
PMID- 11013720
TI - Amperometric glucose biosensor based on sol-gel organic-inorganic hybrid
material.
AB - A new type of sol-gel organic-inorganic hybrid material was developed and used
for the production of biosensors. This material is composed of silica sol and a
grafting copolymer of poly(vinyl alcohol) with 4-vinylpyridine. It prevents the
cracking of conventional sol-gel-derived glasses and eliminates the swelling of
the hydrogel. The optimum composition of the hybrid material was first examined,
and then glucose oxidase was immobilized in this matrix to demonstrate its
application. The characteristics of the biosensor were studied by cyclic
voltammetry and chronoamperometry. The biosensor exhibited a series of good
properties: high sensitivity (600 nA mmol-1 L-1), short response time (11 s) and
remarkable long-term stability in storage (at least 5 months). In addition, the
characteristics of the second-generation biosensor with the use of
tetrathiafulvalene as a mediator were discussed.
PMID- 11013721
TI - Counting of single protein molecules at interfaces and application of this
technique in early-stage diagnosis.
AB - The fluorescence-based detection and counting of single protein molecules after
specific binding to antibodies at interfaces is presented. A diode laser was used
as the excitation source. The unspecific binding at the interface has been
reduced to a level of only 0.1% of the maximum signal level. At present, the
detection limit of this molecule-counting process is in the range of 10(-17)
mol/L, and the dynamic range of the signal corresponds to 7 orders of magnitude
of antigen concentration, but these values are not limiting. As a preliminary
application in early-stage diagnosis, we have investigated the detection of a
single cardiac actin molecule in human plasma, which is of interest in myocardial
infarction diagnosis.
PMID- 11013722
TI - Direct analysis of single rat peritoneal mast cells with laser
vaporization/ionization mass spectrometry.
AB - A linear time-of-flight mass spectrometer was used as a detector for flow
cytometry. These two techniques were coupled by a laser vaporization/ionization
interface. The estimated mass detection limit of the combined system was 20 amol
of serotonin standard with one laser pulse. An aqueous buffer at physiological pH
was used to ensure compatibility with cells. Rat peritoneal mast cells (RPMCs)
were dispensed into the mass spectrometer in a single file confined within a 20
micron-i.d. capillary. By using the mass spectrometer as a detector, no precolumn
staining or derivatization is required. Determination of serotonin and histamine
in individual cells was demonstrated. With this method, hundreds of cells can be
analyzed within a few minutes. The average amounts of histamine and serotonin per
RPMC were found to be 0.75 +/- 0.33 and 0.11 +/- 0.06 fmol, respectively. No
correlation was found between the amounts of the two amines in each cell.
PMID- 11013723
TI - Automation of data collection for matrix-assisted laser desorption/ionization
mass spectrometry using a correlative analysis algorithm.
AB - Automation of data collection in matrix-assisted laser desorption/ionization
(MALDI) mass spectrometry using a correlative analysis algorithm is demonstrated.
This algorithm was employed to compensate for mass spectral jittering in MALDI
data collection (e.g., peak shifts along the m/z axis, signal intensity
deviations, etc.). Several important parameters for performing correlative
analysis, such as the minimum correlation coefficient to be used and number of
mass spectra to acquire prior to correlation, have been investigated and
optimized. In addition, the correlation algorithm improved mass resolution of low
and high-molecular-weight compounds by as much as a factor of 4. Signal
reproducibility in MALDI quantitative analysis also is improved when correlation
is employed for data collection. This data collection algorithm can be used in
conjunction with other instrumental optimization programs to allow for fully
automated MALDI analysis, which is required for the routine applications carried
out in many analytical laboratories.
PMID- 11013724
TI - Capillary isoelectric focusing-electrospray ionization Fourier transform ion
cyclotron resonance mass spectrometry for protein characterization.
AB - On-line combination of capillary isoelectric focusing (CIEF) with electrospray
ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass
spectrometry is demonstrated for high-resolution analysis of model proteins,
human hemoglobin variants, and Escherichia coli proteins. The acquisition of high
resolution mass spectra of hemoglobin beta chains allows direct identification of
hemoglobin variants A and C, differing in molecular mass by 1 Da. Direct mass
determination of cellular proteins separated in the CIEF capillary is achieved
using their isotopic envelopes obtained from ESI-FTICR. The factors which dictate
overall performance of CIEF-ESI-FTICR, including duty cycle, mass resolution,
scan rate, and sensitivity, are discussed in the context of protein variants and
cell lysates analyzed in this study.
PMID- 11013725
TI - SFE plus C18 lipid cleanup method for selective extraction and GC/MS quantitation
of polycyclic aromatic hydrocarbons in biological tissues.
AB - Lipid material represents a potential interference for determination of nonpolar
compounds (e.g., polycyclic aromatic hydrocarbons) in biological tissue samples.
This study reports the development of a selective extraction method using
supercritical CO2 that allows the GC/MS quantitation of PAHs in the presence of a
substantial lipid background. Selective extraction of PAHs relies upon addition
of C18 adsorbent beads to the initial sample slurry. The dried mixture, including
C18 adsorbent, is placed in the supercritical fluid extraction (SFE) chamber.
During the SFE process, lipids are preferentially retained on the C18 beads. This
"SFE plus C18" procedure was developed by first optimizing SFE conditions (100
degrees C, 350 bar) for recovery of PAH standards. PAHs containing added model
lipid compounds (stearic acid and cholesterol) were then subjected to SFE plus
C18 treatment followed by GC/MS analysis. Using this approach, a recovery of 94
100% of PAHs was obtained while only 9-17% of the lipid material present was
coextracted from the same test sample. The developed method is demonstrated to
permit efficient recovery and detection of PAHs spiked into crab tissue, a matrix
with a high lipid content.
PMID- 11013726
TI - Capillary electrochromatography of cannabinoids.
AB - The applicability of capillary electrochromatography (CEC) with photodiode array
UV detection for the analysis of cannabinoids is presented. Baseline separation
of seven cannabinoids (cannabigerol, cannabidiol, cannabinol, delta-9
tetrahydrocannabinol, delta-8-tetrahydrocannabinol, cannabichromene, delta-9
tetrahydrocannabinolic acid) is obtained using a 3-micron CEC Hypersil C18
capillary with an acetonitrile/phosphate (pH 2.57) mobile phase. The effects of
acetonitrile concentration, buffer concentration, voltage, temperature,
stationary phase, and column length on the separation of the cannabinoids were
investigated. Good short- and long-term precision in retention times are
observed, with significant improvement obtained using relative retention times
with cannabinol as reference compound. Although short- and long-term peak area
precisions are poor, satisfactory reproducibility is obtained using relative peak
areas with cannabinol as reference compound. The applicability of the CEC
methodology to drug seizures was demonstrated on marijuana and hashish. Using a
high-sensitivity UV flow cell with an extended path length of 1.2 mm,
concentration sensitivities approaching HPLC were obtained.
PMID- 11013727
TI - Effect of a predetection open segment in the column on speed and selectivity in
capillary electrochromatography.
AB - Columns in capillary electrochromatography (CEC) most commonly have the detection
window located immediately after the retaining frit of the packed segment. Here,
the properties of "duplex" columns having a predetection open segment between the
frit and the detector window are examined with particular regard to the effect of
the relative lengths of the packed and open segments on the separation of
mixtures containing neutral and charged components. This configuration allows the
use of columns with short packed segments in contemporary instruments for rapid
separations. It is shown that, by varying the length of the packed segment, the
balance of chromatographic and electrophoretic forces can be shifted, and the
selectivity can be adjusted if the separation involves the interplay of both
mechanisms. Expressions are presented for estimating the retention time in a
duplex column if the chromatographic and electrophoretic properties of the sample
components are known. The results are expected to facilitate CEC method
development in selection of the respective column segment lengths for optimum
separation.
PMID- 11013728
TI - Analysis of nicotine and its oxidation products in nicotine chewing gum by a
molecularly imprinted solid-phase extraction.
AB - Chromatographic stationary phases showing exceptional selectivity for nicotine
can be prepared by the technique of molecular imprinting. Such phases were used
in the search for a rapid cleanup step for nicotine and some of its oxidation
products in chewing gum formulations. Thus, using an organic mobile phase, the
nicotine analytes from chewing gums dissolved in nonpolar solvent were retained,
whereas the nonpolar matrix eluted close to the void peak. A subsequent switch to
an acidic mobile phase resulted in elution of the analytes as one sharp peak. Due
to weak binding of the less basic oxidation products, other imprinted polymers
were tested, and the solid-phase extraction procedure was optimized. Polymers
were prepared using various functional and cross-linking monomers, templates,
porogens and thermal treatments. This resulted in phases that, when compared with
a nonimprinted or a C18 reversed-phase column, showed significantly higher
recoveries of the analytes. Furthermore, no bleeding of template from the phases
could be detected. The cleanup step was coupled off-line to reversed-phase HPLC,
and the efficiency of the analysis was compared with and without the cleanup
step. Three out of four analytes were quantitatively recovered using the
imprinted phase, whereas, using the nonimprinted phase, only nicotine was
recovered. Without the cleanup step, none of the analytes could be determined
using the reversed-phase HPLC method.
PMID- 11013729
TI - Coupled-column liquid chromatography applied to the trace-level determination of
triazine herbicides and some of their metabolites in water samples.
AB - In the present work, a study is reported of the potential of coupled-column
liquid chromatography (LC) applied to the determination of triazine residues in
environmental water samples. For this purpose, two different techniques have been
compared: on-line trace enrichment followed by LC (SPE-LC) and coupled-column
liquid chromatography (LC-LC). First, a completely automated liquid
chromatographic method based on on-line trace enrichment in a prepacked precolumn
and using diode array detection has been developed for the simultaneous trace
level determination of six triazine herbicides (simazine, cyanazine, atrazine,
terbumeton, terbuthylazine, and terbutryn) and the main atrazine metabolites
(desisopropylatrazine, desethylatrazine, and hydroxyatrazine). After
preconcentration parameters were optimized by testing two different sorbents (C18
and PRP-1) in three cartridges with different dimensions, a sample volume of 100
mL was selected in order to achieve maximal solute preconcentration. Detection
limits lower than 0.1 microgram.L-1 were obtained even for the most polar analyte
(desisopropylatrazine), which presented recoveries of around 30%. The method was
validated by means of recovery experiments in groundwater and surface water
samples spiked with the analytes at different levels (0.2-2 micrograms.L-1).
Afterward, the procedure was successfully applied in a program for monitoring of
triazine residues in surface water carried out in a wet area of Castellon, Spain.
Different triazine herbicides such as simazine, terbumeton, terbuthylazine, and
terbutryn were identified and quantified. The identity of these compounds was
confirmed by their absorption UV spectra and by GC/MS analysis. Finally, two
rapid, sensitive, and selective procedures, previously developed in our
laboratory for the trace-level determination of triazine compounds, both based on
LC-LC, were compared with the former procedure. The SPE-LC approach showed a
considerable improvement in the global sensitivity at the expense of a decrease
in selectivity as well as in sample throughput.
PMID- 11013731
TI - Collision-induced dissociation spectra obtained by Fourier transform ion
cyclotron resonance mass spectrometry using a 13C,15N-doubly depleted protein.
AB - Fourier transform ion cyclotron resonance mass spectra of 13C,15N-doubly depleted
cystatin A M65L, produced by Escherichia coli grown on 99.9% [12C]glucose and
99.99% [14N]ammonium sulfate, showed salient monoisotopic peaks composed of 12C
and 14N. Collision-induced dissociation spectra were obtained by increasing the
capillary-skimmer potential for the electrospray ionization and by extending the
trapping time in a radio frequency-only hexapole ion guide. Fragment ions in the
spectra could be readily assigned to the amino acid sequence, owing to their
markedly improved resolution and sensitivity as compared to those with the
natural isotopic composition. Detailed analyses of the fragmentation patterns,
facilitated by the use of 13C,15N-doubly depleted proteins, enabled the
assignment of approximately 180 fragment ions to the sequence, while natural
isotopic cystatin A allowed the assignment of approximately 110 fragment ions.
Interestingly, no fragmentation was detected between residues 50-61 and 62-67,
which are stretches known to be involved in the antiparallel beta-sheet at the
center of the protein.
PMID- 11013730
TI - Extraction of aldicarb and its metabolites from excreta and gastrointestinal
tissue.
AB - Carbamate insecticide screens often include aldicarb and its oxidative
metabolites, aldicarb sulfoxide (ASX), and aldicarb sulfone (ASN). The rapid
hydrolysis and thermal cleavage of the C-N bond within the carbamate functional
group of these compounds produces nitrile transformation products. Nitriles are
primary transformation products from aldicarb, its sulfoxide, or its sulfone.
However, these nitriles are infrequently monitored. The method reported used
acetonitrile/water extraction and HPLC postcolumn derivitization to determine
aldicarb, ASX, and ASN from avian excreta and from gastrointestinal (GI) tissue.
Recoveries of aldicarb, ASX and ASN from excreta were of 79% +/- 5.4, 120% +/-
7.7, and 93% +/- 6.2, respectively. Recoveries from tissue were 70% +/- 5.0, 80%
+/- 12.1, and 85% +/- 6.7, respectively. The same extraction procedure and a GC
FPD analysis were used to determine nitrile metabolites from the same tissues.
Aldicarb nitrile, ASX nitrile, and ASN nitrile recoveries from excreta were 42%
+/- 2.3, 65% +/- 3.6, and 79% +/- 3.3, respectively. Overall recoveries from
tissue were 29% +/- 3.4, 72% +/- 8.3, and 83% +/- 11.4, respectively. Since
aldicarb, ASX, and ASN are normally detectable in organ tissues for 1-2 days
following exposure, determining the presence of nitrile cleavage products
provides an important forensic tool for evaluating aldicarb exposures.
PMID- 11013732
TI - [Hygienic characteristics of the influence of anthropogenic and natural
geochemical factors on the population health in the South Ural].
AB - The natural and technogenic factors of the industrial towns and rural localities
in the Orenburg Region were differentially analyzed. The modifying effects of
xenobiotics and their complex action on man are considered. The study showed the
high pollution of the atmosphere, the blanket of snow, soil, the trace
composition imbalance of drinking water, foodstuffs, a reduction in biogenic
elements and an increase in toxic elements in the children's substrates (blood,
hair) and high morbidity among the children suggest the presence of the formed
technogenic biogeochemical province in the Eastern zone and, those in terms of
some xenobiotics, in the Central area of the Orenburg Region.
PMID- 11013733
TI - [Microbiological analysis of the state of environment in the Orenburg region].
AB - The frequency of the residual staphylococcal carriage among the children who live
in rural area having different levels and patterns of environmental pollution is
estimated. A relationship is found between the frequency of the residual
staphylococcal carriage and the rate of technogenic pollution of the ambient air.
The findings suggest that the staphylococcal carriage among children may be used
as an index of the unfavorable environment.
PMID- 11013734
TI - [Anthropogenic environmental factors and their role in the occurrence of acute
respiratory diseases].
AB - The incidence of acute respiratory diseases (ARD) in two districts of the
Orenburg Region which have different levels of environmental pollution was
comparatively analyzed. The higher incidence of ARD in the more polluted district
(Kuvandyksky) than in the control one (Belyaevsky). The incidence rate (41.8%) of
ARD correlated with the level of the ambient air pollution by dust, CO, NO2, NF
and fluoride aerosols in the Kuvandyksky district.
PMID- 11013735
TI - [Hygienic evaluation of staphylococcal nasal mucosal biocenosis in school
children of an industrial city].
AB - The results of microbiological spatial monitoring in Orenburg were evaluated. A
biological variety of Staphylococcus on the nasal mucosa of schoolchildren were
detected. The highest proportion of carriage of the pathogen Staphylococcus was
found in different districts of Orenburg, which had the highest air pollution.
PMID- 11013736
TI - [Hygienic aspects of air pollution by sulfur-containing compounds].
AB - The physiological and biochemical states of children and adults who resided in
the vicinity of the sulphide-containing gas processing plant were studied. The
chemical agents emitted by the plant were found to have adverse effects of the
children's functional status, namely, decreased vital capacity of the lung,
mental performance, retarded sensomotor responses, altered enzymatic system
activity.
PMID- 11013737
TI - [Hygienic assessment of the effects of drinking water on the population's
health].
AB - The paper presents the quality of drinking water. The carcinogenic risk of water
and the coefficient of its toxic effect were calculated. The findings determine
the priority of the pollutants detected in the drinking water, estimate the
carcinogenic risk of water to be 1.4 per 10,000 population. It is recommended to
revise specifications for the drinking water of dichloromethane,
dichloroethylene, dioctyl phthalate and acrylonitrile.
PMID- 11013738
TI - [Organic pollution of the Ural river in the area of open water supply of
Orenburg].
AB - The water from the Ural river contains about 230 organic chemical substances,
including especially hazardous pollutants. The levels of some chemicals are 2 to
13 times higher than their maximum allowable concentrations. It is necessary to
use reliable methods for water treatment at waterworks to lower the levels of
drinking water pollutants.
PMID- 11013739
TI - [Effect of thermal power stations on the sanitary and biological conditions of
water reservoirs].
AB - Discharge of thermal waters from power stations can result in the development of
thermophilic microorganisms in the water reservoirs and increased water
pollution. Increased water temperature changes relationships between lysozyme
active and antilysozyme-active bacteria. The quality of water gets worse.
PMID- 11013740
TI - [Hygienic aspects of the use of compact plants for sewage treatment in small
localities].
AB - The waste-water system of small localities is an important measure for their
sanitary well-being. At present, the firm "Ekobios" produces and installs block
module plants for sewage treatment in small localities.
PMID- 11013741
TI - [Hygienic characteristics of work conditions during primary metallurgic
processing of natural alloy ores].
AB - Natural alloy ores contribute to specific pollution of the industrial environment
in the blast-furnace department. The latter is characterized by elevated humidity
and SO2, the higher incidence of blood circulatory disorders among the workers.
PMID- 11013742
TI - [Role of environmental factors of an industrial city in the etiology of
cardiovascular diseases in children].
AB - The prevalence of cardiovascular diseases among 2840 children aged 6 to 15 years
and 7000 neonates in two Orenburg districts was studied. High environmental
pollution in one of the study districts promotes the high spread of
cardiovascular diseases among children.
PMID- 11013743
TI - [Preschool children's health in towns with different levels of environmental
pollution].
AB - A total of 3497 preschool children residing in the towns having with different
man-made burden were examined. The study showed that most children referred to
Health Groups 2 and 3. In the town with higher environmental pollution there were
a larger proportion of children with dysfunctions of different organs and systems
and higher incidence of diseases, including respiratory allergoses, etc.
PMID- 11013744
TI - [Regional features of the immune status of schoolchildren in the Orenburg
region].
AB - Immunity was studied in 319 schoolchildren from the Orenburg Region. They were
found to have lower blood levels of leucocytes and T lymphocytes. It is suggested
that imbalance of traces (mainly copper and zinc) is a cause of these changes.
PMID- 11013745
TI - [Hygienic assessment of physical and psychophysiologic development of children
residing in the area of emissions of Orenburg gas-producing plants].
AB - The children and adolescents residing in rural settlements located in the
vicinity of sites of industrial extraction and processing of hydrogen sulphide
containing gas were studied. The drinking water and ambient air in these
settlements were shown to be polluted. Low indices of the children's mental,
physiological, and physical development were revealed.
PMID- 11013746
TI - [Biochemical parameters of children residing in an area of high-level technogenic
load].
AB - Pollution of the ambient air and drinking water in two comparable regions was
investigated. Twenty four metals and traces were found in the children's hair.
Higher methemoglobin was found in the blood of the children residing in the
higher polluted areas. Decreased concentrations of ascorbic acid were detected in
the urine of the same children. It is recommended to develop prophylactic
measures to protect children's health.
PMID- 11013747
TI - [Radio-ecological and genetic assessment of late consequences of Totsk nuclear
explosion].
AB - Radio-ecological and cytogenetic assessments were made in the vicinity of Totsk
nuclear explosion in the Orenburg Region. Increased contents of radioactive
isotopes Cs and Pu were detected in the soil. A comparative cytogenetic analysis
indicated that the population continued to be exposed to radioactive agents.
PMID- 11013748
TI - [Health status of children living in rural localities in the area of Totsk
nuclear explosion].
AB - The paper presents late outcomes of radiation exposure of 3205 children aged 6-17
years from native persons residing in the areas exposed to radiation 40 years
ago. The spread of noncommunicable diseases in the children from the polluted
area is 92%. Organic abnormalities are prevalent among them. These include
thyroid hyperplasia, lymphadenopathy, gastrointestinal, cardiovascular, and other
diseases. Thus, the environmental radiological situation in the southern Urals
and the Orenburg Region is poor.
PMID- 11013749
TI - [Comparative characteristics of environmental factors of rural localities in the
area of Totsk nuclear explosion].
AB - Environmental pollution of rural settlements in the vicinity of Totsk nuclear
explosion was investigated. The findings show that the blanket of snow, soil and
drinking water in the polluted area did not differ from those in the control
district. High levels of stable strontium in the soil and drinking water and
those of iodine in the water were detected. The concentrations of plutonium-239,
240 and cesium-137 in the soil were higher than the levels of global sediments
and the baseline values of cesium-137 for the Orenburg Region.
PMID- 11013750
TI - [Contribution of physical factors to the complex anthropogenic load in an
industrial town].
AB - The paper provides evidence for the increasing significance of noise and
electromagnetic fields. The correlation coefficients between urban noise and the
incidence of digestive diseases were found to be 0.84, those between noise and
complication pregnancy were 0.83, those between noise perinatal pathology was
0.79, those between electromagnetic exposure (EME) and neuropsychopathy, EME and
cataract, and EME and circulatory disorders were 0.71, 0.91, and 0.78,
respectively.
PMID- 11013751
TI - [Comprehensive hygienic assessment of anthropogenic pollution of development
lands of an industrial town].
AB - Pollution of the ambient air, soil, and drinking water in the Orenburg districts
was studied. Comprehensive hygienic assessment revealed high man-made pollution
of development lands of the environment, industrial districts of Orenburg town in
particular.
PMID- 11013752
TI - [Epidemiologic and immunologic parameters in the assessment of endemic goiter in
the Orenburg region].
AB - Epidemiological investigations were carried out in 2328 children in the districts
of the Orenburg district. Iodine deficiency was detected in the children living
in the districts having low concentrations in the water and foodstuffs. There was
a deviation of immunological parameters from the normal values in the children of
the same districts.
PMID- 11013753
TI - [Comprehensive hygienic assessment of environmental pollution in rural localities
in the area affected by the Orenburg gas processing plant].
AB - Comprehensive analysis of environmental pollution was made in 15 rural
settlements of Orenburgsky and Perevolotsky districts located in the vicinity of
gas-processing works. The ambient air, the blanket of snow, and drinking water
were assessed for pollution. The drinking water and ambient air in vicinity of
the works were found to be polluted by toxic substances.
PMID- 11013754
TI - The molecular evolution of Trypanosomatidae.
AB - In the absence of a fossil record, theories relating to the evolution of protozoa
have, for most of the twentieth century, been based on morphological and life
cycle data despite their known limitations. However, recent advances in molecular
methodology, notably the wide availability of accurate, automated DNA sequencing,
have made it possible to deduce the evolutionary relationships of extant species
from their genes. This paper focuses on new findings concerning the evolution of
the Trypanosomatidae, based on the ever-expanding body of molecular data now
available. Classically, the evolution of digenetic parasitism in kinetoplastids
has centred around two opposing theories--invertebrate first or vertebrate first-
depending on which was the original host of the monogenetic parasite. However,
data supporting a close phylogenetic relationship between genera of monogenetic
insect parasites and digenetic vertebrate parasites challenge the simplicity of
these hypotheses and suggest that the transition may not have been a major
evolutionary barrier. The implications of these observations for the evolution of
parasitism within the group are discussed. Phylogenetic analysis of a diverse
selection of trypanosomatid species suggests that the genus Trypanosoma is
monophyletic and that the human parasites, T. brucei, T. cruzi and Leishmania
spp., have fundamentally different patterns of evolution. T. brucei clusters with
mammalian trypanosomes of African origin, suggesting an evolutionary history
confined to Africa. T. cruzi shows association with trypanosomes from bats, T.
rangeli, and trypanosomes from a range of South American mammals and an
Australian kangaroo. The origins of most parasites within this clade lie in South
America and Australia, suggesting an ancient southern super-continent origin for
T. cruzi, possibly in marsupials. The divergence between the Leishmania and
Trypanosoma lineages is also ancient. The topology of Leishmania phylogenies
suggests an independent transition to digenetic parasitism, a neotropical origin
and an early tertiary radiation of the parasite.
PMID- 11013755
TI - Transovarial transmission in the microsporidia.
AB - The microsporidia are an ancient and diverse group of protists which have many
unusual characteristics. These include prokaryotic-like 70s ribosomes, enclosed
nuclear division, a lack of mitochondria and complex life cycles which frequently
involve vertical transmission. This use of vertical transmission is unparalleled
by other protists and is seen only among bacterial endosymbionts and sex ratio
distorters and in host cell organelles. Transovarially transmitted microsporidia
can have unusual and profound effects on host population sex ratios. We here
consider the mechanisms of transovarial transmission and its implications for
parasite evolution. We review parasite/host relationships and the evolution of
virulence under transovarial transmission and consider the implications of these
parasites for host ecology and evolution.
PMID- 11013756
TI - Adhesive secretions in the Platyhelminthes.
AB - This review is the first to draw together knowledge about bioadhesives secreted
by a group of parasites. Mechanisms of mechanical attachment are well known among
parasites, but some can also attach to host surfaces by chemical means using a
thin layer of adhesive material secreted at the parasite-host interface.
Attachment by adhesives to living surfaces has not been studied in detail
previously. A significant volume of research has determined much about the
chemistry and nature of bioadhesives secreted by various marine
macroinvertebrates from different phyla for attachment to inert substrates.
Mussels and barnacles are sessile and adhere permanently, whereas starfish
display temporary but firm adhesion during locomotion, feeding and burrowing. We
focus on the Platyhelminthes that comprises the largely free-living Turbellaria
and the wholly parasitic Monogenea, Cestoda, Digenea and Aspidogastrea. The term
tissue adhesion is introduced to describe attachment by adhesives to epithelial
surfaces such as fish epidermis and the lining of the vertebrate gut. These
living layers regenerate rapidly, secrete mucus, are a site for immune activity
and are therefore especially hostile environments for organisms that inhabit
them, presenting a significant challenge for adhesion. Not all platyhelminths
adhere to living surfaces and types of adhesion to inert substrates by the free
living turbellarians are also reviewed. Tissue adhesion is particularly well
exemplified by monopisthocotylean monogeneans, parasites that are especially
mobile as larvae, juveniles and adults on the epidermis of the body and gill
surfaces of fish. These monogeneans secrete adhesives from the anterior end when
they move from site to site, but some have secondarily developed adhesives at the
posterior end to supplement or replace mechanical attachment by hooks and/or by
suction. The temporary but tenacious anterior adhesives of monogeneans display
remarkable properties of instant attachment to and detachment from their host
fish surfaces. In contrast to the mobility of turbellarians and
monopisthocotylean monogeneans and the simplicity of their direct life cycles,
the largely endoparasitic Cestoda and Digenea are considered to be less mobile as
adults. The complex cestode and digenean life cycles, involving intermediate
hosts, place different demands on their various stages. Diverse, mostly anterior,
gland cells in larvae, metacestodes and adults of the true tapeworms (Eucestoda),
and in larval and adult Gyrocotylidea and Amphilinidea are reviewed. Conspicuous
gland cells, mostly but not exclusively at the anterior end, in miracidia,
cercariae and adults of digeneans and in cotylocidia and adults of
aspidogastreans are also reviewed. Unlike turbellarians and monogeneans, accounts
of unequivocal adhesive secretions in the Cestoda, but especially in the Digenea
and Aspidogastrea, are relatively rare. The primary purpose of many conspicuous
glands in the different stages of these mostly endoparasitic flatworms is for
penetration into, or escape from, different hosts in their life cycle. We provide
a detailed review of current knowledge about adhesion (in the sense of a thin
layer of chemical material) in the Platyhelminthes including uses among eggs,
larval, juvenile and adult stages. Information on structure, morphology and
ultrastructure of the various adhesive systems that have been described is
reviewed. Application of the 'duo gland' model is discussed. Comparisons are made
between the little that is known about the chemistry of flatworm adhesives and
the significant knowledge of the chemical nature of other invertebrate
bioadhesives, especially those from marine macroinvertebrates. The potential
importance of adhesives in parasitism is discussed. (ABSTRACT TRUNCATED)
PMID- 11013757
TI - The use of ultrasound in schistosomiasis.
AB - Ultrasound was introduced in the 1970s as a method to detect schistosomal
pathology both at hospital and field level. It has since been established as a
safe, rapid, non-invasive and relatively inexpensive technique for assessing
schistosomiasis-related lesions in individual patients and in community surveys.
It can be used to validate laboratory tests to measure morbidity and provides an
opportunity to visualize the evolution of pathological lesions after treatment.
The interpretation of ultrasound imaging depends on the experience of the
investigators and it may not be the ideal tool to detect early lesions of the
affected organs. This paper reviews and critically discusses the present
knowledge of morbidity due to the different types of schistosomiasis as it can be
observed using ultrasound, with special reference to its use as a diagnostic and
monitoring tool in field surveys. It analyses the practical use, benefits and
drawbacks of ultrasound investigations to assess pathological lesions due to
schistosomiasis in relation to other diagnostic tools. The role of ultrasound
investigations among other monitoring approaches in control programmes is
discussed in the context of rational control strategies.
PMID- 11013758
TI - Ascaris and ascariasis.
AB - In recent years much new information has been obtained about the epidemiology,
population biology and public health significance of infections of Ascaris
lumbricoides in humans. Results from experimental infections of A. suum in pigs
have helped to elucidate the observations made in the community on human
ascariasis. The main purpose of the review is to see how new information may
contribute to further acceptance of ascariasis as a serious contributor to ill
health and so to the design and implementation of sustainable control programmes
intended to reduce the morbidity due to infection with A. lumbricoides.
Eradication is neither a realistic nor prudent aim given the current shortage of
appropriate sanitation in many countries where ascariasis is endemic. A
substantial body of evidence shows that for the four common species of soil
transmitted nematode, including A. lumbricoides, regular administration of broad
spectrum anthelminthic drugs to children attending primary schools is a cost
effective means of controlling the infections. Anthelminthic drugs must be of
proven quality and efficacy and health professionals should be prepared to detect
and manage drug resistance should that emerge. Despite a deeper understanding of
the immune response of a variety of hosts to infections with either A.
lumbricoides or A. suum there is at present little prospect of an effective
vaccine against ascariasis. The relationship between A. lumbricoides and A. suum
is addressed, particularly since both species, if they are indeed separate
species, occur in people and their pigs in many communities.
PMID- 11013759
TI - HIV therapeutics: past, present, and future.
PMID- 11013760
TI - HIV drug resistance and viral fitness.
PMID- 11013761
TI - Inhibitors of HIV-1 reverse transcriptase.
PMID- 11013762
TI - HIV-1 protease: maturation, enzyme specificity, and drug resistance.
PMID- 11013763
TI - HIV-1 integrase inhibitors: past, present, and future.
PMID- 11013764
TI - Selection of HIV replication inhibitors: chemistry and biology.
PMID- 11013765
TI - Therapies directed against the Rev axis of HIV autoregulation.
PMID- 11013766
TI - HIV-1 gene therapy: promise for the future.
PMID- 11013767
TI - Assessment of HIV vaccine development: past, present, and future.
PMID- 11013768
TI - HIV-1-associated central nervous system dysfunction.
AB - Despite more than 15 years of extensive investigative efforts, a complete
understanding of the neurological consequences of HIV-1 CNS infection remains
elusive. Although the resources of numerous investigators have been focused on
studies of HIV-1-associated CNS disease, the complex nature of the disease
processes that underlie the clinical, pathological, and cellular manifestations
of HIV-1 CNS infection have required a larger volume of studies than was
initially envisioned. Several major areas remain as the focus of current research
efforts. One of the more pressing issues facing researchers and clinicians alike
is the search for correlates to the development of HIV-1-associated CNS
neuropathology and the onset of HIVD. Although numerous parameters have been
studied, none have been shown to be absolute predictors or markers of HIV-1
related CNS dysfunction. The identification of solid correlates of HIVD is an
important goal that would permit clinical identification of individuals at risk
for developing potentially crippling, life-threatening CNS abnormalities and
would facilitate early treatment of nascent neurological problems. A more
complete comprehension of the cellular foundations of CNS dysfunction and HIVD is
also a fundamental part of strategies designed to treat or prevent HIV-1
associated CNS disease. Future investigations will strive to expand the body of
knowledge concerning the complex interactions between infected and uninfected
neuroglial cells and the roles of numerous cytokines, chemokines, and other
soluble agents that are deregulated during HIV-1 CNS infection. In particular, a
thorough understanding of the mechanisms of neurotoxicity may facilitate the
development of new therapies that alleviate or eliminate the clinical
consequences of CNS infection. Finally, investigators will continue to study HIVD
within the context of single and combination drug therapies used in the treatment
of HIV-1 infection and AIDS. As newer and more effective systemic treatments for
HIV-1 infection and AIDS are introduced, the effects of these treatments on the
onset, incidence, and severity of HIVD will also require intensive study. The
impact of drug therapies on the ability of the CNS to act as an HIV-1 reservoir
will also need to be addressed. Introduction of each new drug or drug combination
will necessitate studies of drug penetration into the CNS and efficacy against
the development of CNS abnormalities. Furthermore, as more effective treatments
prolong the lifespan of individuals infected with HIV-1, the impact of extended
survival on the occurrence and severity of HIVD will also require further
investigations. The quest for answers to these and other questions will be
complicated by the diversity of experimental systems used to study different
aspects of HIV-1 CNS infection and HIVD. Each system has its own unique strengths
and weaknesses. Clinical observations provide a continuous spectrum of
symptomatic findings but reveal little about the underlying mechanisms of
disease. In vivo imaging techniques, such as CT and MRI, also provide a continuum
of observations, but the images are limited in their resolution.
Neuropathological examinations of postmortem HIV-1-infected brains offer gross,
cellular, and molecular views (including phenotypic and genotypic analyses of CNS
viral isolates) of the diseased brain, but only provide a snapshot of the end
stage neurologic dysfunction. Studies that rely on animal surrogates for HIV-1,
including SIV, simian-HIV (SHIV), feline immunodeficiency virus (FIV), visna
virus, and HIV-1 SCID-hu models, permit experimental protocols that cannot be
carried out in humans, but are limited by the fidelity with which each virus and
animal model emulates the conditions and events observed in the human host.
Finally, in vitro techniques, which include the use of primary cells and cell
lines, adult or fetal human cell cultures, and BBB barrier model systems, are
also convenient means by which aspe
PMID- 11013769
TI - Molecular mechanisms of human immunodeficiency virus type 1 mother-infant
transmission.
PMID- 11013770
TI - Molecular epidemiology of HIV-1: an example of Asia.
PMID- 11013771
TI - Simian immunodeficiency virus infection of monkeys as a model system for the
study of AIDS pathogenesis, treatment, and prevention.
AB - As presented in this review, there are a number of different models of both
natural and experimental infection of monkeys with primate lentiviruses. There
are numerous different viruses and multiple different monkey species, making for
a potentially large number of different combinations. The fact that each
different combination of virus isolate and host macaque species may show
different behavior underscores the need to understand the different models and
their key features. On the one hand, this diversity of systems underscores the
need to provide some standardization of the systems used for certain kinds of
studies, such as vaccine evaluations, in order to facilitate the comparison of
results obtained in different experiments, but in essentially the same
experimental system. On the other hand, the rich diversity of different systems,
with different features and behaviors, represents a tremendous resource, among
other things allowing the investigator to select the system that best
recapitulates particular aspects of human HIV infection for study in a relevant
nonhuman primate model. Such studies have provided, and may be expected to
continue to provide, important insights to guide HIV treatment and vaccine
development in the future.
PMID- 11013772
TI - Animal models for AIDS pathogenesis.
PMID- 11013773
TI - [The laryngeal mask in pediatric adenotonsillectomy. A meta-analysis of medical
studies].
AB - Anaesthesia both for adenotomy (AT) and for tonsillectomy (TE) frequently
presents a challenge. On one hand, children scheduled for adenotomy often have
upper airway infections and are thus at risk of laryngo- and bronchospasm; on the
other hand the ENT surgeon and the anaesthetist have to share the "workspace" in
the patient's mouth. Since the succinyl choline debate in the early 1990s, the
question of the best muscle relaxant has gone hand in hand with that of the most
appropriate means of securing the airway. The concept of the laryngeal mask as
airway was initially greeted with scepticism. Following several years' use of the
mask for this purpose in AT and TE in young children, we report our experience
and summarise the literature on this topic. The laryngeal mask represents a safe
alternative to intubation, provided there is close cooperation with the ENT
surgeon.
PMID- 11013774
TI - [Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta
analysis of randomized controlled studies].
AB - OBJECTIVE: Randomised controlled trials investigating the efficacy of
dexamethasone alone or in combination with other antiemetics to prevent
postoperative nausea and vomiting (PONV) were included in a meta-analysis to
estimate the relative efficacy of these treatments. METHODS: Studies were
systematically searched using Medline, EMBASE, the Cochrane-Library, and by
manual screening the reference lists and current issues of locally available
anaesthesia journals. Studies identified were divided into four different groups.
For each subgroup an independent analysis was performed: 1. Dexamethasone vs.
placebo, 2. Dexamethasone + other antiemetic vs. other antiemetic alone, 3.
Dexamethasone + other antiemetic vs. dexamethasone alone, 4. Dexamethasone vs.
other antiemetics. The main end point in each study was defined as complete
absence of nausea, retching, and vomiting after prophylactic antiemetic
treatment. The pooled odds-ratios, the relative risk (RR) and the numbers-needed
to-treat (NNT) with their corresponding 95%-confidence intervals (given in
parentheses) were calculated using a random effects model. RESULTS: A total of 26
studies with 2561 patients were analysed. 1. As a sole antiemetic agent
dexamethasone is superior to placebo to prevent PONV (RR: 0.49 (0.15-0.42); NNT:
3.4 (2.5-5.3)). 2. When dexamethasone and an other antiemetic (e.g. a 5-HT3
antagonist) are combined this drug combination is significantly more effective
than the single antiemetic without dexamethasone (RR: 0.60 (0.46-0.78); NNT: 7.3
(5.7-10.2)). 3. A similar result was obtained when the dexamethasone combination
was compared with dexamethasone alone. The combination is statistically superior
(RR: 0.16 (0.08-0.32); NNT: 3.2 (2.2-6.3)). 4. Dexamethasone was usually compared
with 5-HT3-antagonist and to a less extends also with dopamine antagonists.
Summarising these studies, there was no significant difference concerning
effectiveness (RR: 1.35 (0.99-1.85); NNT: 10.6 (5.6-92.6)). CONCLUSION:
Dexamethasone has antiemetics effects that are superior to placebo treatment and
are comparable with conventional antiemetic agents (e.g. 5-HT3-antagonist,
dopamine antagonists). The drug is especially useful in combination with other
antiemetics and increases the efficacy of the antiemetic partner drug.
PMID- 11013775
TI - [Effectiveness of morphine by periarticular injections after shoulder
arthroscopy].
AB - Peripheral opioid receptors have been found in inflamed synovia and the analgesic
effect of intra-articularly administered morphine after arthroscopic knee surgery
has been proven. There is controversy about efficacy of intraarticular morphine
after shoulder arthroscopy. Thirty-two patients with impingement syndrome
underwent subacromial decompression in the course of arthroscopic shoulder
surgery. At the end of the operation morphine (5 mg) or saline was injected
periarticularly. Pain intensity (rest and passive mobilisation) was recorded
after recovery and after 1,2,4, and 24 hours (Numeric Rating Scale); the use of
rescue medication (piritramide by patient controlled analgesia) was noted. No
relevant pain reduction was apparent in the morphine group. Piritramide
consumption was identical in both groups (19.7 +/- 16 mg vs. 19.8 +/- 19 mg). We
conclude that periarticularly administered morphine in arthroscopic subacromial
decompression in the dosage applied in this study does exert no relevant
analgesic effect. This is possibly due to the fact that either subacromial
tissue, despite of chronic inflammation, does not show the same reagibility as
synovia or it is a problem of the nearly complete resection of the subacromial
bursa.
PMID- 11013776
TI - [Pediatric emergencies. An epidemiologic study of mobile care units in
Innsbruck].
AB - OBJECTIVES: We studied the epidemiology and outcome of prehospital pediatric
emergencies treated by a physician-staffed mobile intensive care unit (MICU).
METHODS: A 3-year retrospective analysis for the period 1991-1993. RESULTS:
Children under the age of 15 years comprised 5.1% of the patients treated by the
MICU (372/7423), 87.4% of whom were not in a life-threatening condition. The most
common emergencies were: trauma (30.4%), febrile seizure (27.7%), and subglottal
laryngitis (12.6%). In 44.6% of cases there was no medical indication for the
MICU. Intubation at the scene was required by 17 patients (4.6%), and 11 (3.0%)
underwent cardiopulmonary resuscitation following prehospital cardiac arrest; two
children were successfully resuscitated but died in hospital. A total of 217
(61.3%) were admitted to the ward, 9 of these to a critical care unit. The
average length of stay was 4.9 days, and 94.5% of patients were discharged in
good health. CONCLUSION: Prehospital pediatric emergencies are rare and seldom
life-threatening. Continuing education in pediatric emergency care is important
for emergency physicians.
PMID- 11013777
TI - [Establishment of a national database for ICU-associated infections. First
results from the "Krankenhaus-Infections-Surveillance-System" (KISS)].
AB - OBJECTIVES: To establish a surveillance system as an element of internal quality
management, participating intensive care units (ICUs) report their ICU-associated
infection surveillance data for aggregation into a national database. METHODS: In
order to provide data on ICU-associated infections, a nosocomial surveillance
system in German intensive care units (Krankenhaus-Infections-Surveillance-System
(KISS)) started in 1997. The method of data collection is based on the (adult)
ICU surveillance component from the National Nosocomial Infections Surveillance
(NNIS)-System. Until now 113 German ICUs (most of them medical/surgical ICUs)
were included in this system. We continuously collected and calculated the data
from site-specific infections (device-associated pneumonias, blood stream
infections and urinary tract infections). RESULTS: There are now a total of
393,177 patient-days (100,015 patients) among them 176,415 ventilator-days,
295,221 central line-days and 316,799 urinary catheter-days in the data base. The
data analysis showed the following device-associated infection rates: 11.2
pneumonias/1000 ventilator-days, 1.8 primary bloodstream infections/1000 central
line-days and 4.0 urinary tract infections/1000 urinary catheter-days.
CONCLUSION: The project has reached high interest in Germany and animated more
ICUs to take part or to apply the same method in order to use the reference data
for comparison.
PMID- 11013778
TI - [The historical development of intensive care in Germany. Contemporary
reflections. 18. Development of hygiene in intensive care].
PMID- 11013779
TI - [ESA 2000].
PMID- 11013780
TI - [Preclinical management of patients with stroke. Remarks and reply to the paper
of H.-J. Hennes et al., Anaesthesist 1999) 48: 858-70].
PMID- 11013781
TI - [Perioperative infusion therapy in abdominal surgery].
PMID- 11013782
TI - [Tourniquets and muscle relaxation].
PMID- 11013783
TI - [Pulmonary gas exchange in anesthesia].
PMID- 11013784
TI - Prostate cancer. What men want from their family physicians.
PMID- 11013785
TI - Privileging and consultation in maternity and newborn care. Maternity and Newborn
Care Committee.
PMID- 11013786
TI - Concerns about the critical appraisal of the role of H pylori in dyspepsia.
PMID- 11013787
TI - Be careful about drawing conclusions.
PMID- 11013788
TI - Don't shoot the messenger.
PMID- 11013789
TI - Tips from a retired family physician.
PMID- 11013790
TI - Canadian Family Physician: through a glass darkly.
PMID- 11013791
TI - Which drugs are contraindicated during breastfeeding? Practice guidelines.
AB - QUESTION: Many breastfeeding mothers are concerned about taking medications that
might affect their babies. Are there any guidelines on which drugs are safe?
ANSWER: Only a few drugs pose a clinically significant risk to breastfed babies.
In general, antineoplastics, drugs of abuse, some anticonvulsants, ergot
alkaloids, and radiopharmaceuticals should not be taken, and levels of
amiodarone, cyclosporine, and lithium should be monitored.
PMID- 11013792
TI - Ophthaproblem. Peripheral corneal thinning secondary to rheumatoid arthritis.
PMID- 11013793
TI - Radial head fracture.
PMID- 11013794
TI - Restless legs syndrome.
PMID- 11013795
TI - Short report: what do men with prostate cancer want to know?
PMID- 11013796
TI - [International Prostate Symptom Scale. Evaluation of the usefulness of a French
version].
AB - OBJECTIVE: To evaluate the usefulness of a French-language version of the
International Prostate Symptom Scale (I-PSS) by measuring, on this scale and on
the quality of life index, the scores of patients with benign prostatic
hyperplasia before and after prostate surgery. METHOD: The questionnaire was
completed by 14 men, mostly between 60 and 80 years old, 24 hours before surgery
and 1 month and 3 months after surgery. RESULTS: The French-language scale worked
well. Scores changed from 19.1 before surgery to 7.5 3 months after surgery for
prostate symptoms and from 8.5 to 4.5 for quality of life. CONCLUSION: This
version of the questionnaire is a valid tool for evaluating prostate symptoms
reported by French-speaking people.
PMID- 11013797
TI - Referral of children with otitis media. Do family physicians and pediatricians
agree?
AB - OBJECTIVE: To determine factors influencing family physicians' and pediatricians'
decisions to refer children with recurrent acute otitis media (RAOM) and otitis
media with effusion (OME) to otolaryngologists for an opinion about tympanostomy
tube insertion. DESIGN: Mailed survey. SETTING: Physicians' practices in Ontario.
PARTICIPANTS: Random sample of 1459 family physicians and all 775 pediatricians
in the province. MAIN OUTCOME MEASURES: Physicians' reports of the influence of
17 factors on decisions to refer (more likely, no influence, less likely to
refer) and number of episodes of otitis media, months with effusion, level of
hearing loss, or months of continuous antibiotics without improvement prompting
referral. RESULTS: Physicians agreed (> 80% concordance) on six out of 17 factors
as indications for referring children with RAOM or OME. Opinions about the
importance of other factors varied widely. Family physicians would refer children
with otitis media after fewer episodes of illness, fewer months of effusion,
lower levels of hearing loss, and fewer months of prophylactic antibiotic therapy
than pediatricians (all P < .001). Pediatricians would prescribe continuous
antibiotics longer (11.8 weeks) than family physicians (8.9 weeks, P < .0001),
which correlated with lower referral thresholds for family physicians.
CONCLUSION: Family physicians' and pediatricians' self-reported referral
practices for surgical opinions on children with otitis media varied
considerably. These observations raise questions about the consistency of care
for children with otitis media and whether revised clinical guidelines would be
helpful.
PMID- 11013798
TI - Is respite care available for chronically ill seniors?
AB - OBJECTIVE: To determine family physicians' perceptions of how available respite
care is and how easy it is to refer chronically ill older people to it, and to
examine their opinions of respite care. DESIGN: Mailed survey to family
physicians on the Thames Valley Family Practice Research Unit's mailing list.
SETTING: London, Ont, and surrounding area. PARTICIPANTS: Of the 448 surveys
mailed to eligible physicians, 288 were completed and returned for a response
rate of 64.3%. MAIN OUTCOME MEASURES: Respondents' perceptions of how available
respite care is and how easy it is to refer chronically ill older people to it
and their opinions on the effectiveness of respite care. RESULTS: More than half
the respondents reported that outpatient respite care is always available, but
how available depended on practice location. Inpatient respite care was reported
as less available. More than half the respondents found referral to respite care
difficult. Respondents were very positive about the role of respite services in
long-term care and in lowering caregiver stress. Respondents' perceptions varied
according to where they had attended medical school. Their perceptions of respite
care's role in long-term care and in helping patients remain at home were
influenced by whether they thought respite care was available. CONCLUSION: Family
physicians need education in the value of respite services for their chronically
ill older patients and their families. Physicians also need information on the
respite services available and strategies for accessing them. Our findings
suggest a need for greater attention to regional discrepancies in availability of
services.
PMID- 11013799
TI - Treating obesity. Lost cause or new opportunity?
AB - OBJECTIVE: To review therapies for treating obese patients. QUALITY OF EVIDENCE:
Advice in this paper is based mainly on the results of randomized controlled
trials. Some data from smaller, more physiologic studies are included. When
appropriate, advice is based on consensus. MAIN MESSAGE: Recent medical evidence
indicates that a modest weight loss (5% to 10%) can alleviate symptoms of obesity
related comorbidity. Treatment of obesity should be comprehensive and integrated
into a multi-component approach and should involve both patients and their
families. The main challenge of obesity is maintaining a reduced weight.
CONCLUSION: A multi-component approach to treating obesity can help make
treatment less frustrating and more rewarding for patients and physicians.
PMID- 11013800
TI - Status epilepticus. Current concepts and management.
AB - OBJECTIVE: To inform primary care physicians about current issues around
generalized convulsive status epilepticus (GCSE) emphasizing definition,
pathophysiology, treatment, and prognosis. QUALITY OF EVIDENCE: MEDLINE (1994 to
1999) provided 479 references using the MeSH terms "status epilepticus" and
"treatment." From these we selected 30 English-language articles covering
clinical aspects, treatment, and animal research. Key source documents from
previous years and information from modern textbooks and recent symposia were
also included. MAIN MESSAGE: Generalized convulsive status epilepticus continues
to be a medical emergency with high morbidity and mortality. It must be managed
promptly and effectively. The operational definition of GCSE is a seizure that
lasts longer than 5 minutes or two or more seizures between which patients do not
recover. Main differential diagnosis is nonepileptic status. Intravenous therapy
with combined lorazepam and phenytoin is the initial treatment of choice. Other
preferred medications are diazepam, midazolam, and propofol. Some of these
medications should be considered before arrival at hospital. Prognosis of GCSE is
determined by underlying cause, delay in adequate treatment, and comorbidity.
Patients with GCSE lasting longer than 30 minutes require intensive care and
electroencephalogram monitoring. CONCLUSION: Intravenous lorazepam and phenytoin
are currently the most effective drugs for initial management of GCSE. Timely
administration of antiepileptic medication can prevent development of GCSE in
some patients with known epilepsy. Main differential diagnosis is nonepileptic
status.
PMID- 11013802
TI - Canadians' smoking behaviour. Results from the National Population Health Survey.
Centre for Chronic Disease Prevention and Control.
PMID- 11013801
TI - Scaphoid fracture. Review of diagnostic tests and treatment.
AB - OBJECTIVE: To help make diagnosis and treatment of scaphoid fracture more precise
by review of published evidence. QUALITY OF EVIDENCE: MEDLINE was searched using
the terms "scaphoid," "carpal navicular," "fracture," "computed tomography,"
"bone scan," and "scintigraphy." Most papers were case-series observational
reports. Papers were cited if the case series was large or if there was a high
degree of agreement among several observers. The main recommendation for change
in treatment of scaphoid fracture is based on two randomized clinical trials
involving more than 1000 patients with proven scaphoid fracture. MAIN MESSAGE:
Fracture of the scaphoid requires a specific mechanism of injury. "Snuffbox"
tenderness is not specific for scaphoid fracture and is not the most useful
physical finding; other physical findings provide more specific evidence for or
against scaphoid fracture. Physical examination remains the basis of initial
treatment and should be thorough and meticulous. X-ray films must be of high
quality and should be examined carefully for bone and soft tissue signs of
fracture. A Colles'-type short arm cast is adequate for treating common
undisplaced scaphoid waist fractures; the thumb need not be immobilized. For
suspected scaphoid fractures, without radiologic evidence of fracture, treating
symptoms is likely sufficient. CONCLUSION: Evidence found in the literature can
be used to improve diagnostic accuracy for scaphoid fractures, to optimize
treatment for these injuries, and to reduce unnecessary immobilization and
disability for patients.
PMID- 11013803
TI - Doctor, heal thyself.
PMID- 11013804
TI - Lessons for Canada. The 13th International AIDS Conference.
PMID- 11013805
TI - [Surgical and multimodal therapy of pseudomyxoma peritonei].
AB - The rarity of Pseudomyxoma peritonei, its complex biology and the remaining
inconsistencies in terminology all contribute to rendering therapeutic
recommendations a difficult task. In principle, a multimodal concept combining
cytoreductive surgery with peri- and postoperative intraperitoneal chemotherapy
constitutes the preferable treatment. Initially, surgical peritonectomy aims to
achieve the complete removal of tumor cells at the macroscopic level.
Subsequently in the early postoperative phase when the absence of adhesions
allows for a homogeneous intraabdominal spread of cytotoxic drugs,
intraperitoneal application of 5-fluorouracil and mitomycin C represents the most
solidly established treatment. Therapeutic failures are often due to
insufficiently radical cytoreductive surgery or a lack of homogeneous
distribution of cytotoxic drugs in the abdomen. In view of the rarity of their
condition, patients with Pseudomyxoma peritonei should be treated at or in
conjunction with specialized centers. Only such a "center-oriented" approach will
secure the standardization of treatment and help to clarify unsettled therapeutic
questions. The development of improved therapeutic concepts will depend on
concise histopathological classification. Already at present therapeutic
decisions should not only be be based on the clinical aspect of a "mucinous
abdomen" but should be guided by the pathological differentiation between
disseminated peritoneal adenomucinosis (DPAM), with a relatively good prognosis,
and the more aggressive peritoneal mucinous carcinomatosis (PMCA).
PMID- 11013806
TI - [Malignant mesothelioma of the pleura, pericardium and peritoneum. 1: Etiology,
pathogenesis, pathology].
AB - The incidence of primary malignant neoplasms of the pleura, the pericardium and
the peritoneum in Germany has been rising since about the mid-1980s. A continuing
rise is expected until about 2020, predominantly due to the peak of asbestos
processing in Germany between 1965 and 1980. About 90% of the mesotheliomas
stored in the files of the German Mesothelioma Registry in Bochum are asbestos
related and therefore possibly due to occupational exposure that may be
compensated by the professional associations. More than 500 mesotheliomas
annually can be diagnosed in the German Mesothelioma Registry. In this first part
of the series on mesotheliomas, current concepts on etiology and pathogenesis as
well as diagnostic procedures and standards are discussed. At the present,
specific chromosomal or genetic defects that constantly give rise to a
mesothelioma are not known. The initiation and progression of malignant
mesotheliomas is a highly complex mechanism that is based on individual genetic
alterations. A reliable diagnosis is the basis for therapeutic, prognostic and
medicolegal consequences; in general, it can be achieved by thoracoscopic
inspection with selected biopsy. Surgery may gain a more important role in the
therapy of malignant tumors of serosal membranes not only in palliative, but also
in potential curative approaches if the diagnosis can be made at earlier tumor
stages.
PMID- 11013807
TI - [Mesothelioma of the pleura and peritoneum. Diagnostic and therapeutic sequelae].
AB - In patients with pleural or peritoneal mesothelioma, surgery is a technically
difficult procedure. Whereas those rare forms of localized pleural mesotheliomy
are being detected incidentally and can be cured by complete resection, most
patients with diffuse malignant mesothelioma present with an advanced stage of
disease. Most of these patients survive less than 12 months irrespective of the
treatment modality. For diffuse pleural mesothelioma, some favorable prognostic
factors were identified: IMIG (International Mesothelioma Interest Group), stages
I and II, epithelial type, age under 50, female gender. In IMIG stages I and II,
extended pleuropneumonectomy followed by chemo- and/or radiotherapy is
recommended. For this subset of patients, a median survival time of between 20
and 30 months is reported. Pleurectomy and decortication are recommended as
palliative surgical strategies against pleural effusion. In patients with
technically inoperable infiltration of the thoracic wall, irradiation is helpful;
sometimes partial remission and relief of pain can be achieved by chemotherapy.
PMID- 11013808
TI - [The desmoid problem].
AB - Desmoid tumors (DTs) are rare nonmetastasizing neoplasms, occurring both
sporadically and in the context of familial adenomatous polyposis (FAP). DTs show
an unpredictable natural course with approximately 10% demonstrating a severely
aggressive growth pattern, whereas others regress spontaneously. Surgery appears
to have a triggering effect on desmoid growth, but is unavoidable in patients
with FAP requiring prophylactic colectomy. Treatment recommendations remain
controversial. Surgery may only be regarded as an option if a safety margin of at
least 2 cm is guaranteed. Even under these circumstances recurrence rates are
very high. Debulking operations invariably lead to a boost towards more
aggressive growth. Most issues regarding DTs are contradictory, reflecting the
lack of any systematic approach to the disease. One way out of this dilemma is
the establishment of a clinical classification as a first step towards
standardized therapy.
PMID- 11013809
TI - [Extra-abdominal fibromatosis--extra-abdominal desmoid. Review and personal
experiences].
AB - Extraabdominal desmoids represent one group of deep fibromatoses. These
aggressive nonmetastasizing tumorlike lesions have a strong tendency to local
infiltration, with a recurrence rate of about 40%. Trauma, hormones and heredity
have been implicated as etiologic factors. Shoulder, chest wall, back and thigh
are favored sites. By combination of different diagnostic procedures the number
of differential diagnoses can be reduced to only a few. While in former times
surgery was thought to be the only kind of therapy, nowadays adjuvant procedures
like radiation, hormonal therapy and also chemotherapy are becoming more and more
important. Amputation or other mutilating procedures should be done only if the
tumor recurs repeatedly.
PMID- 11013810
TI - [Evidence-based recommendations for perioperative antibiotic prophylaxis].
AB - The aim of perioperative antibiotic prophylaxis (PAP) is to reduce postoperative
complications. In 1994 specialist American companies developed a PAP quality
standard, whereby individual recommendations were divided into categories
according to the degree of evidence. These recommendations have been tabulated
and supplemented with the results of new, randomized, controlled studies.
PMID- 11013811
TI - [Abdominal compartment syndrome: prevention and treatment].
AB - Abdominal compartment syndrome is defined by increased intraabdominal pressure
above 20 mmHg with increased pulmonary peak pressure and oliguria. In primary
abdominal compartment syndrome the increased intraabdominal pressure is caused
directly by peritonitis, ileus or abdominal and pelvic trauma. Secondary
compartment syndrome is a result of forced closure of the abdominal wall after
abdominal surgery. The effects are decreased cardiac output, pulmonary
atelectasis, oliguria to anuria and hepatic as well as intestinal reduction of
perfusion. Effective monitoring is done by standardised measuring of urinary
bladder pressure. Normal values are between 0 and 7 cm H2O, after elective
laparotomies 5-12 cm H(2)0. Above 25 cm H(2)0 they are definitely pathological.
For the prevention and therapy of manifested abdominal compartment syndrome the
application of a laparostomy using a resorbable mesh is recommended. Between 1988
and 1999 we applied a laparostomy to lower the intraabdominal pressure in 377
patients. In 16% of the cases it was indicated by primary abdominal compartment
syndrome with a bladder pressure of 31 +/- 4 cm H(2)0 preoperatively, which could
be lowered to 17 +/- 4 cm H(2)0 by laparostomy. An early reconstruction of the
abdominal wall could be performed in 18% of the cases. CONCLUSIONS: The abdominal
compartment syndrome is an often underestimated problem in abdominal surgery
involving multiple organ systems. The temporary laparostomy lowering
intraabdominal pressure rather than a forced closure of the abdominal wall should
be used in all circumstances.
PMID- 11013812
TI - [Idiopathic megacolon. New findings on histopathology and musculo-mechanical
causes].
AB - Nineteen native surgical specimens of an idiopathic megacolon were
histopathologically investigated and a lack of the tendon-like collagen III
movement net of circular and longitudinal muscles observed, including a lack of
the connective tissue layer of myenteric plexus. This disease of the muscularis
propria could be considered as a desmolysis, a hypoplastic or an aplastic
desmosis. With reference to the normal muscle mechanics of the gut, it is shown
that the pathogenetic principle of the idiopathic megacolon consists in absence
of the tendon-like connective tissue net in the muscularis propria which results
in a lack of peristalsis of the gut, despite of a regular enteric innervation.
This finding demonstrates that an idiopathic megacolon can be histopathologically
verified in whole-mount biopsies and referred for curative surgical treatment.
PMID- 11013813
TI - [Can continence function after rectal resection be prognostically estimated?].
AB - AIM: To determine clinical and physiologic parameters enabling the prognosis of
continence after protective ileostomy closure secondary to rectal resection for
rectal cancer. METHODS: Patients who had undergone rectal resection (n = 65, of
whom 24 had had radiochemotherapy) were evaluated by clinical examination,
anorectal manometry and orthograde contrast enema before ileostomy closure.
Continence was evaluated by clinical findings 91 +/- 52 weeks after stoma closure
with the help of standardized questionnaires and classified according to the
Wexner continence score. The relationship between findings before stoma closure
and continence score was calculated with Pearson's correlation coefficient.
RESULTS: Correlations were found to be significant between the continence score
and the level of anastomosis (r = -0.58, p < 0.001), median resting pressure (r =
-0.52, p < 0.001), rectal compliance (r = -0.43, p < 0.001). Additionally,
radiochemotherapy impairs continence (p = 0.0001). Correlations were not
significant between continence and functional sphincter length, squeeze pressure,
threshold for perception, urge and maximal tolerable volume, and continence for
semiliquid contrast medium. CONCLUSION: Incontinence after rectum resection is
multifactorial: the level of anastomosis, resting pressure, rectal compliance and
radiochemotherapy all play a dominant role. Based on these findings, the
continence score can be calculated before closure of a diverting ileostomy by
applying multivariate analysis with the help of the following formula: Continence
score = 18.23 - 0.94 x level of anastomosis - 0.18 x resting pressure + 3.72 x
radiochemotherapy.
PMID- 11013814
TI - [Laparoscopic hernia therapy (TAPP) as a teaching operation].
AB - INTRODUCTION: Because of an increasing number of endoscopic hernia procedures, it
is important to look into the possibility of standardizing these techniques
helping surgeons to acquire the operative skills necessary. MATERIAL AND METHODS:
To discuss these aspects, the documented data on TAPP operations that have been
carried out in this department since 1993 were analyzed. The results of teaching
procedures were compared with those of experts after they had gotten past the
learning and development curve. RESULTS: A total of 778 teaching procedures were
performed by 10 surgeons with an individual experience of 30.5 operations
(median). Before starting the first procedure, 89 were done by assistants
operating the camera. The morbidity of teaching operations was 1.9% compared to
1.4% for those performed by experts. After a median follow-up of 23 months there
were two recurrences (0.23%) in the expert group and none in the teaching group
(follow-up 16 months). CONCLUSION: Because of the potentials of standardization
of the TAPP technique, the results of teaching were equal to expert operations.
Therefore, TAPP is suitable for application in a routine setting.
PMID- 11013816
TI - [Quality of life and subjective evaluation of outcome quality 3 years after
laparoscopic antireflux surgery].
AB - PURPOSE: Evaluation of quality of life data and patient satisfaction to estimate
the outcome of laparoscopic antireflux surgery (LARS) is nowadays an important
issue, the long-term outcome of this has not yet received much attention.
METHODS: In the present study we evaluated the outcome of quality of life data of
70 patients who underwent "floppy" Nissen fundoplication at our institute 3 years
after surgery. Quality of life was evaluated with the Gastrointestinal Quality of
Life Index (GIQLI). Additionally the subjectivity and objectivity of the quality
of the procedure and possible side effects were evaluated with a questionnaire.
RESULTS: Three years after laparoscopic Nissen fundoplication, patients gave
their quality of life (GIQLI) in an overall score of 123.9 points. This is
comparable to 122.6 points in the normal population. There was no difference
detectable in the subdimensions of GIQLI. Ninety-eight percent of the patients
estimated their satisfaction with the procedure as excellent or good and would
undergo surgery again if necessary. Four patients suffered from minimal side
effects from the procedure, but had no decrease in their quality of life. None of
the patients needed antireflux medications postoperatively. Laparoscopic redo
fundoplication was performed in two patients 3 months after initial surgery
because of persisting dysphagia. CONCLUSION: The efficacy and long-term outcome
of treatment of gastroesophageal reflux disease with laparoscopic "floppy" Nissen
fundoplication can be evaluated by objective testing, but also by subjective
judgment of the patient and with an evaluation of quality of life.
PMID- 11013815
TI - [Effects of strength- and endurance oriented training during regional
chemotherapy in metastatic rectal carcinoma. Case report as a contribution to
surgical oncology].
AB - OBJECTIVE: How does adjuvant training of strength and endurance influence the
muscular, cardial, respiratory, immunological systems, and the quality of life
during intrahepatical chemotherapy in a veteran athlete with liver metastasis
after resection of a carcinoma of the rectum. PATIENT AND METHOD: A 58-year-old
athlete with metastatic carcinoma of the rectum (pT3, N0, M-liver, G2) underwent
regional chemotherapy (folinic acid, 5-fluorouracil) via an intrahepatic port
system. Six cycles with 5 days each were applied. During the intervals between
cycles (14 days), beginning in the 6th postoperative week, a strength and
endurance training (duration 13 weeks) was carried out twice weekly with an
intensity of 40-60% of the maximum postoperative individual power and endurance
(evaluated with weight and treadmill exercise tests and measurement of lactate).
Before and after chemotherapy, an echocardiogram, resting and exercise
electrocardiogram, lung function, natural killer cells and the gastrointestinal
quality of life index (GLQI) was evaluated. After chemotherapy was finished, the
effects of training were assumed. RESULTS: Strength increased between 0% and
144%. Endurance improvement was measured on the last comparable submaximal
intensity step, expressed by reduction of heart rate and lactate concentration by
10 and 21.5%, respectively, improvement of lung function regarding FEV 1 and FCV
by 12.9 and 11.3%, respectively, and VC IN 11.4%. The relative count of natural
killer cells increased by 27.2%, and the GLQI improved from 109 points
(pathologic) to 129 points (normal). CONCLUSION: There were positive effects on
muscular and cardial mechanisms of adaptation and on illness-related quality of
life. Postoperative sports activity during regional chemotherapy is possible.
PMID- 11013817
TI - [Tolerance of early oral feeding after operations of the lower gastrointestinal
tract].
AB - INTRODUCTION: Oral feeding is usually offered following surgery of the lower
gastrointestinal tract when clinical signs of normal intestinal motility are
present. However, some studies have shown that early oral feeding is well
tolerated with low morbidity. METHODS: A prospective cohort study was performed
to evaluate whether early oral feeding according to a standardized schedule is
tolerated under normal clinical circumstances. One hundred consecutive patients
following small- or large-bowel resection with anastomosis were offered fluids on
post-operative day 1, soup on post-operative day 2, mashed food on post-operative
day 3 and a regular diet on post-operative day 4. Parenteral nutrition was only
given if necessary. Tolerance of oral feeding and the amount of food were checked
twice a day. End points of the study were nausea (VAS score 1-100), vomiting (>
200 ml), reinsertion of a nasogastric tube, level of food intake, parenteral
nutrition (ml), appetite and well-being. RESULTS: Loop ileostomies were done in
21 patients, colonic resections above the sigmoid in 32, and sigmoid and rectal
resections in 47. The average age was 63 +/- 13 years. The frequency of nausea
was less than 30% and of vomiting less than 10%. Only in two cases was a
nasogastric tube inserted. Forty-three percent of all patients tolerated feeding
very well according to the schedule. On post-operative day 3 more than 60%
tolerated oral intake, on post-operative day 4, 74% and on post-operative day 5,
88%. Only 22% of the patients needed parenteral fluids on post-operative day 4.
The first bowel movement was noted after 2.8 +/- 1.1 days. Surgical complications
were documented in 18 patients and general complications in 6 patients.
CONCLUSION: Most patients tolerated early oral feeding very well according to the
schedule with low morbidity. Therefore, early feeding is now a substantial
component of the postoperative treatment following small- or large-bowel
resections.
PMID- 11013818
TI - [Development of obstructive jaundice after hemorrhage into a benign, non
parasitic liver cyst].
AB - Benign, non-parasitic liver cysts are usually asymptomatic and found incidentally
by abdominal ultrasound or CT scan. We present the case of a 68-year-old patient
who showed obstructive jaundice due to a hemorrhagic liver cyst compressing the
choledochal duct. Due to the location of the cyst in the porta hepatis with
partial compression of central liver vessels and the meanwhile organized
hematoma, operative therapy was preferred in order to prevent secondary
complications such as portal vein thrombosis and to exclude a malignant neoplasm.
PMID- 11013819
TI - [Paratesticular sarcomas. Case report of leiomyosarcoma].
AB - Paratesticular sarcomas are rare. We discuss this entity with the aid of a case
report and the existing literature. The therapy of these tumors includes
resection and possible adjuvant radiotherapy. Rhabdomyosarcomas are an exception,
because they also show a good response to chemotherapy.
PMID- 11013820
TI - [Surgical principles in stomach carcinoma].
PMID- 11013821
TI - [Does history still have current applications?].
PMID- 11013822
TI - [Patient information for and about the hospital].
PMID- 11013823
TI - [Occupational evaluation--assessment of the most recent law regarding
occupational jurisprudence on form and content].
PMID- 11013824
TI - Effect of blocking alpha-adrenoreceptors on the noradrenaline-induced changes in
mouse uterine motility during different terms of pregnancy: in situ experiments.
PMID- 11013825
TI - Paradoxical sleep considerably contributes to the night decrease in brain
temperature in hibernating mammals in summer.
PMID- 11013826
TI - Seasonal changes in the effect of L-DOPA and 5-OTP on the integrative activity of
suslik brain.
PMID- 11013828
TI - Adrenergic regulation of the circulating pool of phagocytic cells in acute
stress.
PMID- 11013827
TI - Reinforcement effect of glucocorticoid hormones.
PMID- 11013829
TI - The effect of 6-hydroxydopamine on elicitation of long-term sensitization in the
edible snail: electrophysiological study.
PMID- 11013830
TI - Expression of alpha 2-adrenoreceptors in the brain cortex depends on the
noradrenaline concentration.
PMID- 11013831
TI - Synthetic pineal peptide inhibits growth of spontaneous tumors and increases
lifespan in mice.
PMID- 11013832
TI - Critical bandwidths of different types of neurons in the mouse auditory midbrain.
PMID- 11013833
TI - Effect of short-term pulse adaptation to hypobaric hypoxia on epileptiform
seizures and rheological blood properties in KM rats.
PMID- 11013834
TI - A pineal peptide increases lifespan in Drosophila melanogaster.
PMID- 11013835
TI - DNA damage and tumor cell death caused by the combined effect of vitamins B12b
and C.
PMID- 11013837
TI - Contribution of induced autolysis to digestion in secondary consumers
(examplified by hydrobionts).
PMID- 11013836
TI - Studies of synthetic attractants of the Siberian moth Dendrolimus superans Butl.
(Lepidoptera: Lasiocampidae).
PMID- 11013838
TI - Dwarf males and reproductive tactics in the mikizha Parasalmo mykiss Walbaum
(Salmonidae, Salmoniformes) from the Kamchatka peninsula.
PMID- 11013839
TI - Ocular rectus muscles in the hypophyseal fossa of the basisphenoid in the permian
theriodont Suchogorgon golubevi (Reptilia).
PMID- 11013840
TI - Do mammalian karyotypes evolve towards equalization of relative chromosome
lengths?
PMID- 11013841
TI - Disruption of the dynamics of food passage through the digestive tract in red
voles (Clethrionomys rutilus) dwelling in an area near oil and gas extraction.
PMID- 11013842
TI - Eye structure in arrow worms (Chaetognatha).
PMID- 11013843
TI - Biocatalysis of matter transfer in a microcosm is inhibited by a contaminant:
effects of a surfactant on Limnea stagnalis.
PMID- 11013844
TI - Unusual hair structure in sloths (Edentata: Bradypodidae).
PMID- 11013845
TI - Pedomorphosis in fossil and modern testudinata (exemplified by Trionychidae).
PMID- 11013846
TI - The insect as a consumer: a model of efficient behavior.
PMID- 11013847
TI - Morphogenetic response of the water vole (Arvicola terrestris L.) to atypical
environmental conditions.
PMID- 11013848
TI - Immunogenetic characteristics of patients with stomach cancer and predominant
activity of either sympathetic or parasympathetic autonomic nervous system.
PMID- 11013850
TI - Conodont (Euconodontophyles), a living fossil.
PMID- 11013849
TI - Effect of the agouti gene on the hypothalamic-hypophyseal-adrenal system in mice.
PMID- 11013851
TI - A new class of mutations in Drosophila melanogaster.
PMID- 11013852
TI - A simple model of the spatial dynamics of the consumer-resource system.
PMID- 11013853
TI - Induction of potassium transport in wheat sprout roots by low potassium content
in the medium.
PMID- 11013854
TI - Suppression of symbiotic digestion in red voles (Clethrionomys rutilus) as a
result of anthropogenic impact.
PMID- 11013855
TI - Protein synthesis inhibitors applied for a short time cause resumption of the
resting state of NIH 3T3 strain cells more effectively than growth factors.
PMID- 11013856
TI - Effect of ATP on different Ca2+ channels in PC12 pheochromocytoma cells.
PMID- 11013857
TI - [Serum tyrosine in children with phenylketonuria and mild hyperphenylalaninemia].
AB - Serum tyrosine concentration, Phe/Tyr scores and psychomotor/mental development
scores were analysed in 32 children with phenylketonuria (PKU) and 39 with mild
hyperphenylalaninaemia. Observation period included the first 6 years of life.
Tendency to tyrosine deficiency was observed; stronger in dietary treated PKU
patients than in those with mild hyperphenylalaninaemia. Statistically
significant differences between patient groups were found only in 3 and 6 years
old children (lower tyrosine values in PKU patients). It was observed that
evaluation of Phe/Tyr score value might be usefull in differentiation between PKU
and mild hyperphenylalaninaemia. Moreover, the above score may help in the
evaluation of hypo- and hyperalimentation state in the course of dietary
treatment. The level of tyrosine deficiency in the analysed patient groups did
not influence their normal intellectual development.
PMID- 11013858
TI - [Sudden infant death syndrome (SIDS). Prevention recommendations].
AB - Etiology of sudden infant death syndrome still remains unknown. However, the risk
factors are established and serve as a base for creating the recommendations for
infants' sleep safety and SIDS prevention.
PMID- 11013859
TI - [Apnea states in infants, anxiety of parents and pediatricians, and home
monitoring of respiration in children].
AB - In order to determine parental reasons of the use of home apnea/respiration
monitors and to estimate the grounds of these decisions correspondence contact
was achieved with the parents of 71 infants monitored by means of the APNEAL-1
device. Filled up questionnaires were the source of data regarding the families
(structure, health practices, mothers' age and education, course of pregnancy and
delivery), monitored infants (birth weight, Apgar score, apnea events) and the
reasons of monitoring. Also opinions concerning monitor usefulness and
performance were gathered. The majority of our families (> 97%) consisted of both
parents, their socio-economic status was medium (52.11%) or good (46.48%) and
they were residents of cities (88.73%). Cigarette smoking was present in 22
families (31%) with 13 smoking mothers (18.31%). Mothers' mean age was 29.11
years (SD 4.84), 45% of them had high school education and 36.62%-university
education. As many as 45% of the pregnancies had a pathological course and 34.3%
were terminated by a preterm delivery. Mean birth weight of monitored children
was 2914.93 g (SD 971.4), mean Apgar score was 8.31 (SD 2.46). More than 60% of
children were breast fed during the first six months of life, and 30% of them-
during first year of life. Bed sharing was reported in only 8% of children. Apnea
episodes were observed in 30 infants (42.25 of whole group), in 20 of them only
during the neonatal period. More apnea episodes were present in premature infants
(48% of premature versus 30% of full term infants). Only 12 children (16.9% of
whole group) manifested apnea events during the monitoring period. However,
almost all the parents (97%) had a high opinion of the role played by the monitor
(mean monitoring time 7.12 months, SD 4.44). In 27 families (38%) a cause of
monitoring was a preceeding apnea event. The decision of remaining parents was
based exclusively on fear. This fear was justified only in a small number of
families (previous SIDS victim, GER). Numerous children were monitored solely on
the basis of information of apnea existence in children. Such a difficult to
accept monitoring reason probably has its source in inappropriate family health
education.
PMID- 11013860
TI - [Endoscopic evaluation of upper gastrointestinal tract mucosa in children with
food hypersensitivity].
AB - The authors compared clinical symptoms with morphological and endoscopic picture
of upper gastrointestinal tract mucosa in 48 children at pre-school and school
age with established food allergy.
PMID- 11013861
TI - [Production of gastrointestinal mucosa cytokines in Helicobacter pylori
infection].
AB - The authors determined the role of cytokines in the pathogenesis of gastric
mucous membrane inflammation in patients with H. pylori infection. Cytokines play
an important role in the pathogenesis of mucous inflammation in secretory and
gastromotoric disorders.
PMID- 11013862
TI - [Preoperative diagnosis and surgical treatment tactics for anorectal
malformations in light of personal observations].
AB - The article presents contemporary views on classification, diagnostics and
surgical treatment of congenital anorectal anomalies. The model of one stage or
multi stage repair depending on the kind of defect and the necessity the anal
sphincter muscles reconstruction was discussed. It was noticed that the most
important independent factor which can have influence on the functional outcome
is a normally developed sacral bone. The objective method of evaluation of the
sacrum proposed by Schneider Hospital in New York is presented.
PMID- 11013863
TI - [The significance of iron in infant development and nutrition. I. Metabolism of
iron].
AB - The role of iron in the child organism, as well as the blood's role in regulating
the iron homeostasis is described on the basis of relevant literature. From
developmental data on Warsaw children and from relevant literature, the child
average body iron content and the child average daily iron requirement, which is
at age 0-0.5, 0.5-1 and 1-2 years 0.51, 0.92 and 0.76 mg for boys and for girls
0.42, 0.86 and 0.74 mg respectively, are calculated. It is noted that the daily
physiological iron loss during the first two years of life can be as much as 50%
of the daily iron requirement. Among the causes of infant iron deficiency are the
greater blood losses during the peri- and postnatal periods, decreased dietary
iron, as well as increased need for iron related to significant body growth. The
loss of one ml of blood in children results in the loss of from 0.33 to 0.66 mg
of iron. On the basis of the changes in body iron content of infants having
various birth weights, it is shown that the quantity of iron needed for proper
development is independent of the birth weight. The quantity of iron required by
premature infants and children with low birth weight is 25-50% greater, after the
infant doubles its birth weight, than that needed by full-term and normal birth
weight infants.
PMID- 11013864
TI - [The significance of iron in development and nutrition of infants. II. Prevention
of iron deficiency].
AB - The symptoms and consequences of iron deficiency in the child are described as
found in the literature. The role of iron in immune processes is presented and it
is noted that there is no proof for the theory of the development of bacterial
infections as a result of giving oral iron supplements. The influence of breast
milk and cow milk on the intestinal uptake and loss of iron is discussed. Feeding
infants formulae or milk-substitute formulae after cessation of breastfeeding
prevents the increased blood loss in the digestive tract, which results from the
introduction of cow's milk. The iron content of selected Polish infant formulae,
follow-on formulae and milk-substitute formulae available on the market are given
and compared with FAO, WHO, ESPGAN and EC recommendations. Results of the
authors' own researches on the iron content of selected Polish powdered whole
cow's milks are presented. The measurements, made by atomic absorption
spectroscopy (AAS), showed that iron content of whole powdered milks ranged from
0.23 to 1.19 mg/dm3. The values do not vary significantly from those in the
literature on the iron content of unboiled cow's milk. It is shown that up to the
point of the doubling of birth weight, formula-fed infants should be fed modified
milk containing at least 2 mg/dm3 of iron. Thereafter infants should receive milk
containing at least 7 mg/dm3 of iron.
PMID- 11013865
TI - [Cryptorchidism--current opinions].
AB - Cryptorchidism is the most common developmental disorder of endocrine organs in
boys. Incidence depends on the age of the child--is the highest in the premature
infants (30%), in term infants 2-5%, in adults 0.3%. Aetiology is still unclear
and it is thought to be multifactorial including: dysgenesis of the testis,
endocrine abnormalities and anatomical block on the way of the descent of the
testis. In 90% of cases the pathology is unilateral. Abnormal localisation of the
testis leads to the histomorphological changes which may be the causes of
complications. The most dangerous are: infertility and neoplasms. The author
presents also the diagnostic methods and therapeutic management in
cryptorchidism.
PMID- 11013866
TI - [Evaluation of total energy balance and food habits of obese children].
AB - Total daily energy expenditure (TDEE) and time spent for activities of different
intensities (heart rate monitoring method), as well as dietary and food habits
(24-hour dietary recall) in two groups of 12-14 year-old boys, including 35 obese
(weight 67.0 kg +/- 9.3, height 162 cm +/- 7.6) and 35 control group boys (weight
46.0 kg +/- 6.5, height 160 cm +/- 7.5) were estimated. Obese boys spent more
time at rest and less time on physical activities than nonobese (p < 0.001). That
resulted in differences of TDEE expressed per unit of body mass (p < 0.001). Time
for sleeping and time in school was not statistically different in the two
groups. The evaluation of nutritional habits indicated that the obese boys, when
compared with controls, had higher energy intake and significantly higher
percentage of fat energy in total energy intake, low intake of fruits and
vegetables and irregular frequency of meals during the day. Diets of boys were
not balanced with respect to calcium and phosphorus.
PMID- 11013867
TI - [Evaluation of iron status in women with pregnancy complicated by tobacco
smoking].
AB - Relatively common iron deficiency in pregnant women is assumed to be enhanced by
cigarette smoking. In the presented studies we determined cotinine in serum and
urine of 75 pregnant women in order to select groups of smoking women and tobacco
abstinence. In the smoking group, a mean concentration of cotinine 1039 +/- 560
mg/L in serum and 1025 +/- 540 mg/L in urine were observed. For assessment of
iron status we determined in serum: iron, iron-binding capacity (TIBC),
transferrin, transferrin saturation, soluble transferrin receptor and ferritin.
In serum of smoking woman in comparison to non smoking, the level of ferritin and
transferrin was higher but non significantly. Significant increase of TIBC (p <
0.05) and decrease of transferrin saturation (p < 0.05) was observed. Therefore
iron deficiency in transport compartment can not be excluded. The concentration
of soluble transferrin receptor was the same in both groups studied. However, in
late pregnancy (above 27 week of gestation) ferritin concentration less than 20
mg/L of serum was observed in 70% of smoking and only in 39% of non smoking women
(p < 0.05). We concluded that cigarette smoking during pregnancy did not have any
effect on the entry of iron-bearing transferrin to cells mediated by soluble
transferrin receptor, but affected the level of iron-storage ferritin, which
leads to iron deficiency in the storage compartment (ID I).
PMID- 11013868
TI - [Molecular diagnosis: principles, tasks and purposes].
AB - Molecular diagnosis is a relatively young discipline and also one of the most
dynamic among clinical laboratory sciences. Molecular genetic diagnosis is the
detection of pathogenic mutations in DNA and RNA samples prepared from at-risk
patients. The paper reviews some problems connected with molecular technicqes,
organization of a reference laboratory and quality assurance system.
PMID- 11013869
TI - [Analysis of mutations in the CFTR gene in patients diagnosed with cystic
fibrosis in Poland].
AB - Polish CF patients were screened extensively for mutations in the CFTR gene.
Screening data demonstrated a high heterogeneity of CFTR mutations in the Polish
population. Total 30 different mutations were characterised in 24 exons or
introns of the gene. Among them, six mutations have been reported for the first
time and submitted to the CF Genetic Analysis Consortium. In addition, 15
different polymorphisms were found, including three new ones. The screening
resulted in 9% increase of the detection rate of CFTR alleles in the tested
population. Frequencies of two of the identified mutations (CFTRdele2,3 and
2184insA) are relatively high (2.6% and 1%, respectively) and justify their
inclusion into routinely screened mutations in genetic testing of Polish CF
population.
PMID- 11013870
TI - [Secular growth trends in children and youth of Warsaw in the last twenty years].
AB - The aim of the study was to preliminarly evaluate the secular trend in Warsaw
children and youth during the last 20 years. Mean values of body height, weight
and chest circumference and weight to height percentile curves of children and
youth aged I month to 18 years, examined in Department of Growth and Development
of Children and Youth of the Institute of Mother and Child in Warsaw in 1976-80
and 1996-99, were compared. Secular changes in body height and weight and
especially in chest circumference were observed in the studied population during
the last 20 years. In children and youth growth acceleration occurred, but in
infants a deceleration was observed. At all ages a slight tendency toward
slimness was visible. The changes in the values of anthropometric growth indices,
which occurred during the last 20 years have shown that there is a need for
prospective growth monitoring and upgrading of growth standards.
PMID- 11013871
TI - [Evaluation of sexual initiation circumstances in youth].
AB - The age of sexual initiation is connected with many factors such as: the age of
biological maturity, temperament, personality, moral standards, family, culture
and place of residence, religion, influence of partner. The aim of the study was
evaluation of the age and circumstances of sexual initiation of youths. The
material were voluntary and anonymous questionnaires. These questionnaires
included multiple choice questions as well as fill in the blank questions. The
questionnaires were given to high-school students. The ages of the 1374
questioned students were between 18 and 20. RESULTS: The age of sexual initiation
was between 16 and 18 years of age. The most frequent place was bed at home
(50.23 to 67.74%). CONCLUSIONS: The age of sexual initiation does not differ from
other European countries. Circumstances of sexual initiation of Poles is similar
to other countries.
PMID- 11013872
TI - [Idiopathic headache in children].
AB - According to literature data, headaches occur in about 40% of preschool children
and up to 70% of the children at school age. Most of the headaches, especially in
school children, are idiopathic. Symptomatic headaches accompanying a diversity
of diseases occur in a small percentage. The idiopathic headaches are the ones in
which the pain is not only the main symptom but also the essence of the disease
itself. Other idiopathic headaches include: migraine, tension-type headache and
Horton headache. The diagnostic and therapeutic problems in idiopathic headaches
are discussed.
PMID- 11013873
TI - [Advances in treatment of congenital gastroschisis based on personal
examinations].
AB - The aim of the study was the definition of standard approach to a newborn with
gastroschisis. The rules of treatment introduced in 1992 enabled the closure of
the abdominal wall primarily in all newborns and made it possible to decrease the
mortality considerably. This was achieved despite the fact that we usually did
not have influence on time and method of delivery or quality of transportation to
our department. In the Department of Pediatric Surgery of Institute Mother and
Child, in the years 1992-1997, twenty three newborns with gastroschisis were
admitted. The standard approach in all patients was the following: insertion of
the catheters to the small bowel through the appenddicocaecostomy and to the
large bowel through the rectum, intraoperative irrigation of the meconium
(mucosolvan), forceful stretching of the abdominal wall, returning of
extraabdominal viscera under control of central venous pressure or middle airway
pressure (anesthesiologic control). In the postoperative period all patients
routinely had controlled ventilation, administration of analgesic drugs,
catecholamines, antibiotics and total parenteral nutrition. Intestinal catheters
were gradually removed every day for irrigations of all levels. Oral nutrition
was started after the return of effective peristalsis. From 23 treated newborns
16 are alive. 7 children died, 4 of them were resuscitated before operation
because of severe general condition. Two patients died because of sepsis in the
second month of life, one because of SIDS (sudden infant death syndrome) in the
third week of life. Sixteen children are followed up. The development of all
children is normal.
PMID- 11013874
TI - [Hearing assessment in children with Pierre-Robin syndrome].
AB - Physical examination of the ear and hearing assessment was carried out in 30
infants with Pierre-Robin syndrome, aged 3 to 8 months. In 93.3% dysfunction of
the Eustachian tube was present. Hearing impairment of perceptive type was found
in 13.3% of these children.
PMID- 11013875
TI - [Nitric oxide (NO)--Nobel prize in medicine and physiology for 1998].
AB - On October 12, 1998. The Nobel Assembly announced the award of the Nobel Prize in
Medicine and Physiology to pharmacologists Robert Furchgott, Louis Ignarro, and
Ferid Murad. The Nobel Committee decided to award the prize for their discoveries
concerning--nitric oxide as a signalling molecule in the cardiovascular system.
Nitric oxide (NO) has a key importance for vascular tonus, acts as a signal
molecule in the nervous system and plays an important function in the
immunological system. Nitric oxide is a multifunction molecule which controls the
blood pressure, modulates gastrointestinal motility. It is produced in abnormal
level intensifies septic shock and destruction of nervous tissue. NO is important
in different branches of medicine. For instance NO gas has been used to reduced
high blood pressure in the lung of infants. Several unknown NO applications in
medicine are waiting for discovery.
PMID- 11013876
TI - Rice in deep water: "how to take heed against a sea of troubles".
AB - Plants are aerobic organisms for which oxygen shortage poses a severe problem.
Waterlogging and flooding are the main causes of anaerobiosis and can lead to
damage or even death of the plant. Rice is well adapted to semi-aquatic
conditions. It is the only cereal that can be grown in flooded areas such as the
great river deltas of Asia. In rice, two major strategies have evolved to cope
with conditions of flooding. One is to escape submergence and thereby avoid
anaerobiosis as much as possible. This is achieved through elongation growth and
through extensive aeration of submerged plant parts by way of internal and
external air spaces. The second adaptation is a metabolic one which includes the
efficient use of carbohydrate resources and maintenance of energy charge when the
cells do become anaerobic. The mainly ethanolic fermentation pathway found in
anaerobic rice avoids acidification of the cytoplasm and thereby contributes to
the maintenance of cell integrity. Genetic analysis indicates that the
submergence tolerance trait, which is based on metabolic changes, is encoded by
only one or a few as yet unidentified gene(s). Identifying these genes is a major
goal in anaerobic stress research.
PMID- 11013877
TI - Flavonoid wing pigments increase attractiveness of female common blue
(Polyommatus icarus) butterflies to mate-searching males.
AB - Common blue butterflies (Polyommatus icarus) sequester flavonoids from their
larval host plants and allocate these UV-absorbing pigments to the wings. In
field experiments using dummies constructed from female butterflies, mate
searching males inspected flavonoid-rich dummies more intensively than those with
little or no flavonoids. Flavonoid content as signalled by UV-wing pattern may
indicate ontogenetically determined female quality or enhance detectability to
males.
PMID- 11013878
TI - Walking on insect paths? Early ommatidial development in the compound eye of the
ancestral crustacean, Triops cancriformis.
PMID- 11013879
TI - Predator odour and its impact on male fertility and reproduction in Phodopus
campbelli hamsters.
AB - This study investigated the influence of cat urine odour in suppressing
development and fertility in Campbell's hamster males. Exposure to this odour
from postnatal day 11 until day 45 (sexual maturation) resulted in reduced sex
organ weights, reduced testosterone levels and in an increase in abnormalities of
the synaptonemal complex in both sex chromosomes and autosomes. Subsequent
breeding experiments revealed a significant decrease in litter size. All these
data indicate a severe effect of predator odour on the breeding success of
potential prey species. It is assumed that these effects are caused by the
sulphurous compounds in the urine; however, the underlying mechanisms are not yet
known.
PMID- 11013880
TI - Free-flight phonotaxis in a parasitoid fly: behavioural thresholds, relative
attraction and susceptibility to noise.
AB - The phonotactic capacity of tachinid flies to acoustically detect and localize a
sound source simulating their cricket host was investigated in a large flight
room. Acoustic measurements were performed to estimate the actual stimulus
delivered to the flies, revealing highly heterogeneous sound fields. When
presented with a simulated cricket song in red or infrared light conditions, the
flies readily flew to the sound source and landed on it. Behavioural phonotactic
thresholds were established as a function of carrier frequency and were found to
coincide well with the frequency of the host's natural song (4.5-5.2 kHz).
Experiments revealed that the same range of frequencies is preferentially
attractive to the free-flying flies, and that the reliability of signal detection
in the presence of noise is best at behaviourally relevant frequencies.
PMID- 11013881
TI - A trail pheromone component of the ant Mayriella overbecki Viehmeyer (Formicidae:
Myrmicinae).
AB - The myrmicine ant Mayriella overbecki lays recruitment trails during foraging and
nest emigrations. The trail pheromone originates from the poison gland. From ten
identified components of the poison gland secretions only methyl 6
methylsalicylate 1 elicited trail following behavior.
PMID- 11013882
TI - Queens and major workers of Acanthomyrmex ferox redistribute nutrients with
trophic eggs.
AB - In Acanthomyrmex ferox, two distinct egg-types are produced: reproductive eggs
that give rise to offspring and trophic eggs that serve to distribute nutrients.
Queens lay both reproductive and trophic eggs, while major and minor workers lay
only trophic eggs in the presence of the queen. The queen lays on average 17% of
the trophic eggs in a colony, while majors and minors produce 42% and 41%,
respectively. The large proportion of trophic egg production by the queen and
soldiers is quite remarkable, since ant queens are expected to focus entirely on
reproduction and majors, which have a defensive function in many species, to be
sterile.
PMID- 11013883
TI - The brain as a photoreceptor: intracerebral ocelli in the firefly.
AB - This paper deals with the structure and function of the intracerebral ocelli in
the caudal area of the brain of the Japanese firefly. A pair of epilaterally
placed specialized pigmented organs was found at the caudal ends of the brains of
the fireflies Luciola cruciata and L. lateralis. On the basis of light and
transmission electron micrographs of both male and female individuals these
organs seemed photoreceptive in nature. Intracellular and extracellular
recordings were obtained from the intracerebral ocelli of the fireflies with
microelectrodes. The physiological evidence revealed that the cells found in the
brain were, indeed, photoreceptors.
PMID- 11013884
TI - Phylogeny of filamentous ascomycetes.
AB - Phylogenetic studies of higher ascomycetes are enhanced by the introduction of
molecular markers. Most studies employed sequences of the SSU rRNA gene, but
recently data from additional genes (RPB2, LSU rRNA) have become available.
Several groups defined by their ascoma-type, such as Pyrenomycetes, are supported
while others, like the Discomycetes, appear to be paraphyletic. The Pezizales
with operculate asci are basal to other eu-ascomycetes, while other Discomycetes
appear to be derived eu-ascomycetes. The reevaluation of classical characters
using molecular data is discussed using three examples. Ascus types are often
regarded as being of major importance in ascomycete systematics, but
prototunicate asci were found to be of poor taxonomic value, since ascomycetes
with prototunicate asci are polyphyletic. The independence of the Agyriales,
assumed from their morphological characters, is supported by sequence data but
the relationship to supposed sister groups remains dubious. The phylogeny of
ascolocularous fungi and their circumscription requires further study. While a
circumscription based on bitunicate asci can be rejected, it remains unclear
whether fungi with ascolocularous ascoma development represent a monophyletic
entity.
PMID- 11013885
TI - Neurosecretion: peptidergic systems in insects.
AB - Insect neuropeptides are produced in less than 1% of the cells of the central
nervous system. Despite this, they are important messenger molecules which
influence nearly all physiological processes, including behaviour. They can act
as transmitters, modulators and classical hormones, and often exhibit pleiotropic
functions when released into the haemolymph. The large number of neuropeptides
that has been identified from some of the model organisms among insects
underlines the complexity of the neurosecretory system; studies about the
coordinated actions of these substances are in their preliminary stages. Recent
advances in insect neuropeptide research will be reviewed here, concentrating on
the distribution of multiple peptide forms in the central nervous system and
adjacent neurohaemal organs, and the role of neuropeptides in eclosion behaviour.
PMID- 11013887
TI - Orientation and navigation during adult transport between nests in the ant
Cataglypis iberica.
AB - Cataglyphis iberica is a polydomous ant species in which adult transports between
nests are frequently observed. When pairs of workers were captured and released
at the same location, the transporters (Ts) field directly towards their
destination nest and reached it in most of the cases. The transportees (Te), on
the other hand, fled in the opposite direction and only a third of them
eventually reached their nest of departure. Additional experiments suggest that
this result may be explained by the fact that the Ts ants have a memory of the
compass direction of the nest they are heading to and that they adjust their
course by using a sequence of memorised landmarks. As regards to the Te, the
reversal of their direction of transport seems to be based essentially on
celestial cues.
PMID- 11013886
TI - Biocompatibility correlation of polymeric materials using human osteosarcoma
cells.
AB - Metal implants are the preferred materials to generate articular prostheses,
plates, or bone pegs in orthopedic surgery. Although titanium and titanium alloys
show a relatively good biocompatibility, clinical experience revealed that
coating of the metallic implant surface may increase the biocompatibility. In a
search for optimum bone implant surfaces, we determined polarity and contact
angle parameters of a variety of polymers and substances and correlated the
findings in a biocompatibility assay using an in vitro bone cell model. We report
that an optimum adherence of SAOS-2 cells to such surfaces and a good vitality
for polymers are characterized by water-based contact angles of 80 degrees and 20
degrees for advancing and receding probes, respectively.
PMID- 11013888
TI - Enzymatic pattern processing.
AB - A table-top prototype has been constructed that uses the enzyme malate
dehydrogenase to recognize input signal patterns. The device is controlled by the
enzyme in response to injection of Mg2+ used as a signaling substance. Output is
monitored spectroscopically. If Mg2+ is injected along either of two signal lines
(i.e., if the input signal pattern is 10 or 01) the device emits an output of 1.
Injection along neither or both lines results in an output of 0. The enzyme in
effect is used as a transform that converts the linearly inseparable exclusive-
or problem into a linearly separable problem.
PMID- 11013889
TI - Pathological alterations typical of human Tay-Sachs disease, in the retina of a
deep-sea fish.
AB - Micrographs of retinas from the deep-sea fish Cataetyx laticeps revealed visual
cells containing membranous whorls in the ellipsoids of the inner segments
resulting from stretching and modifications of the mitochondria membranes and
their cristae. These pathological structures seem to be homologous to the whorls
observed in retinas of human carriers of Tay-Sachs disease. This disease, a
genetic disorder, is found in humans and some mammals. Our findings in fish
suggest that the gene responsible can be found throughout the vertebrate
evolutionary tree, possibly dormant in most taxa.
PMID- 11013890
TI - Light-dependent magnetoreception in birds: the effect of intensity of 565-nm
green light.
AB - In a previous study, Australian silvereyes tested in autumn under monochromatic
565-nm green light at intensities of 2.1 and 7.5 mW m-2 preferred their normal
northerly migratory direction, whereas they showed a significantly different
tendency towards northwest at 15.0 mW m-2. Repeating these experiments in spring
with silvereyes migrating southward, we again observed well-oriented tendencies
in the migratory direction at 2.1 and 7.5 mW m-2. At 15.0 mW m-2, however, the
birds once more preferred northwesterly directions, i.e. their response under
this condition proved to be independent of the migratory direction. This
contradicts the interpretation that monochromatic green light of this high
intensity leads to a rotation of compass information; instead, it appears to
produce sensory input that causes birds to give up their migratory direction in
favor of a fixed direction of as yet unknown origin.
PMID- 11013891
TI - Radio-telemetric evidence of migration in the gregarious but not the solitary
morph of the Mormon cricket (Anabrus simplex: Orthoptera: Tettigoniidae).
AB - The Mormon cricket, Anabrus simplex, is one of just a few species of katydids (or
bushcrickets, Orthoptera: Tettigoniidae) that, like migratory locusts, appear to
have solitary and migratory morphs. Using radio telemetry we studied movements of
individuals of two morphs of this flightless species. Individuals within each
migratory band had similar rates of movements along similar directional headings
whereas solitary individuals moved little and showed little evidence of
directionality in movement. Our results also add to other recent radio-telemetry
studies showing that flightless insects of 1-2 g in mass can be tracked
successfully using these methods.
PMID- 11013892
TI - Seed drops and caches by the harvester ant Messor barbarus: do they contribute to
seed dispersal in Mediterranean grasslands?
AB - To determine whether the harvester ant Messor barbarus acts as a seed disperser
in Mediterranean grasslands, the accuracy level of seed processing was assessed
in the field by quantifying seed drops by loaded foragers. In the vicinity of
exploited seed patches 3 times as many diaspores were found as in controls due to
seed losses by foragers. Over trails, up to 30% of harvested seeds were dropped,
singly, by workers but all were recovered by nestmates within 24 h. Seeds were
also dropped within temporary caches with very few viable diaspores being left
per cache when ants no longer used the trail. Globally, ant-dispersed diaspores
accounted for only 0.1% of seeds harvested by M. barbarus. We discuss the
possible significance for grassland vegetation of harvester-ant-mediated seed
dispersal.
PMID- 11013893
TI - 2,3-dimethyl-5-(2-methylpropyl)pyrazine, a trail pheromone component of
Eutetramorium mocquerysi Emery (1899) (Hymenoptera: Formicidae).
AB - The ant Eutetramorium mocquerysi (Myrmicinae) is endemic to the island of
Madagascar. During foraging and nest emigration the ants lay recruitment trails
with secretions from the poison gland. We identified three pyrazine compounds in
the poison gland secretion: 2,3-dimethyl-5-(2-methylpropyl)pyrazine 1, 2,3
dimethyl-5-(3-methylbutyl)pyrazine 3, 2,3-dimethyl-5-(2-methylbutyl)pyrazine 4.
Only the first component elicited trail-following behavior in the ants. We were
unable to investigate whether the other pyrazine components have a synergistic
function.
PMID- 11013894
TI - [The p300 cognitive event-related potential. I. Theoretical and psychobiologic
perspectives].
AB - The P300 is a positive wave which arises when an attended stimulus is detected.
Its parameters depend on a number of variables, in particular the subject's
mental state, the task that has to be accomplished, the significance of the
stimulus, and the degree of attention. It can be recorded with accuracy, and the
different stages of information processing can therefore be analyzed. The P300
wave shows the modifications in neuronal activity which take place during the
cognitive process: P300 latency provides an indirect indication of the duration
of the processes involved in stimulus discrimination while its amplitude, which
is influenced by a number of variables, provides an index of the intensity of the
energetic activation or arousal involved. The P300 wave consists of several
components which reflect distinct information-processing events (P3a, P3b, P3e, P
SR, P-CR). According to the theoretical models, it is hypothesized that P300
could either represent the adaptation of the working memory to further
environmental input ('context updating'), or indicate a closing process ('context
closure') in information processing. As regards the physiological aspect of P300
and its association with cortical networks, various studies have suggested that
several cortical generators of P300 may co-exist: the medial temporal lobe, the
temporo-parietal junction, and the medial and lateral frontal lobe.
Psychopharmacological studies have shown that different neurotransmitter systems
are involved in the generation and modulation of P300, namely the cholinergic,
noradrenergic, dopaminergic, serotoninergic and gabaergic systems. It appears
that the noradrenergic agonists increase the amplitude of P300, dopaminergic
agonists may have a biphasic effect (increase/reduction), while cholinergic
antagonists and gabaergic agonists reduce P300 amplitude and prolong its latency.
PMID- 11013895
TI - [The p300 cognitive event-related potential. II. Individual variability and
clinical application in psychopathology].
AB - The P300 wave is one of the cognitive components of the event-related potential
(ERP) that is used to investigate the cognitive processes, and which can be used
to study patient populations with a variety of psychiatric disorders. Its
clinical utility has been increased by the identification of factors that
contribute to the variability in its amplitude and latency. However, its value as
a diagnostic index has not been entirely established. It can provide a useful
recording of patients' information processing, and indicate the severity of the
clinical state and its possible evolution. It can also assist in determining what
therapeutic approach to adopt. In the present review, the findings in the
literature concerning interindividual variation in the P300 wave are first
described; several variables significantly influence the amplitude and latency of
this wave, such as age, gender, intelligence and personality. Following this, the
relevance of the data in the literature on the clinical applications of P300 in
psychopathology is examined, including the studies undertaken to obtain an
objective diagnostic index for mental disorders and also those carried out to
assess the problems concerning the interpretation of information connected with
the mental pathologies examined. P300-associated findings on dementia,
schizophrenia, depression, alcoholism, drug addiction, anxiety disorders (panic
disorder, obsessive-compulsive disorder, and post-traumatic stress syndrome) and
on personality disorders (schizoid, antisocial or borderline personality
disorder) have been examined in detail.
PMID- 11013896
TI - The effect of motivational instructions on P300 amplitude.
AB - The aim of this investigation was to determine the effect on P300 amplitude of
instructions aimed at increasing the subject's degree of task involvement. To
this end, two different studies were carried out. In Study 1, 20 university
students were tested with an auditory event-related potential (ERP) oddball
paradigm (target: 1,100 Hz; standard: 1,000 Hz) in two consecutive runs, each
with a different set of instructions; after the first run, subjects were verbally
motivated to increase their level of performance in the second run. In Study 2
(performed 1 year later), ERPs were similarly obtained from the same subjects
during two oddball runs, but this time both tests were preceded by neutral
instructions. The amplitude and latency of N1 and P2 elicited by non-targets and
of N2 and P3 in target waveforms were evaluated. The findings showed that
following motivating instructions, P3 amplitude increased while P3 latency showed
a non-significant decrease. The amplitude of P2 to non-target stimuli--which
could be interpreted as P250--was also affected by the instructions provided. The
overall results suggest that the presentation of motivating instructions is
followed by a higher amount of attentional resources allocated to all stimuli,
and a more efficient evaluation and discrimination of relevant targets. The
implication of these findings for the clinical use of P300 has been discussed.
PMID- 11013897
TI - Predictive value of EEG monitoring during drug withdrawal in children with
cryptogenic partial epilepsy.
AB - In order to evaluate the predictive value of the interictal EEG after
discontinuation of anticonvulsant therapy in children with cryptogenic partial
epilepsy, a prospective study was carried out on 84 children and adolescents who
had been seizure-free for at least 2 years. Twenty-four children (28.6%)
presented one or more relapses. EEG monitoring during drug withdrawal showed
abnormalities in 67% of the patients (16/24) who relapsed with seizures, and in
10% of the patients (6/60) who did not relapse. Our study suggests that in
children who have suffered from partial epilepsy, the detection of paroxysmal
abnormalities during drug withdrawal, in a previously normal EEG is a risk factor
for recurrence of seizures. It is therefore advocated that periodic EEG
monitoring be carried out during the drug withdrawal period, because the presence
of EEG abnormalities is associated with a high probability of seizures occurring
during or after drug discontinuation.
PMID- 11013898
TI - [Evoked mechanical and electrical anal sphincter responses after cortical and
lumbar magnetic stimulation].
AB - In 13 healthy volunteers we recorded electrical and mechanical anal sphincter
(AS) evoked responses. Electrical responses were obtained with surface
electrodes, and mechanical responses by anal manometry; all responses were
compared with those of anterior tibialis. Mechanical evoked responses' latency
and amplitude were calculated. The mean total conduction time of the electrical
responses was 26.07 ms at rest and 23.31 ms with mild contraction (p < 0.003).
After lumbar magnetic stimulations, because of stimulation artefact, electrical
responses couldn't be correctly measured. The mean central conduction time
calculated with mechanical responses was 21.44 ms at rest and 18.81 ms with mild
contraction (p < 0.003). The mean central conduction time to the anterior
tibialis was shorter (14.38 ms; p < 0.003). Evoked mechanical responses',
amplitudes were respectively 128.2 cm H2O (cortical stimulations at rest), 138.8
cm H2O (cortical stimulations with mild contraction) and 133.1 cm H2O (lumbar
stimulations at rest) (NS). Evoked mechanical responses amplitudes were
correlated with the AS maximal voluntary contraction amplitude (p < 10(-4)).
Mechanical motor evoked responses after cortical and lumbar magnetic stimulations
can be recorded and quantified. In anorectal disorders, this technique could be
of major interest for the diagnosis of neurologic lesions versus behavioural
problems.
PMID- 11013899
TI - Expanding the reach of clinical trials.
PMID- 11013900
TI - Reader looking for guidelines/policies on continuous infusion vesicants for
assessments.
PMID- 11013901
TI - Additional issues raised on blood returns and ports.
PMID- 11013902
TI - Thyroid cancer: patients' experiences of receiving iodine-131 therapy.
AB - PURPOSE/OBJECTIVES: To enhance understanding of the experiences and educational
needs of patients receiving iodine-131 (131I) therapy for the treatment of
thyroid cancer. DESIGN: Qualitative design using interpretive description.
SETTING: A 24-bed oncology/acute-care medical unit in a large tertiary hospital
in western Canada. SAMPLE: 5 men and 22 women (18-80 years of age) who have
received 131I therapy in the past two years. METHODS: Unstructured focus group
and telephone interviews and field notes. Interviews were tape-recorded,
transcribed verbatim, and subjected to thematic analysis. FINDINGS: Researchers
elicited four major themes from the analysis: (a) recognizing the totality of the
cancer experience, (b) being isolated, (c) recognizing the totality of the
treatment experience, and (d) understanding barriers to treatment. CONCLUSIONS:
Healthcare providers require a better understanding of thyroid disease and the
treatment and side effects of 131I therapy. Furthermore, educational programs are
required to adequately prepare nurses and patients for future care. IMPLICATIONS
FOR NURSING PRACTICE: A need exists to improve the care and education provided to
patients receiving 131I therapy. In particular, recognition of the totality of
the cancer experience and the need for both staff and patient education were
illustrated. If nurses are to provide comprehensive cancer care, both
psychosocial and physical needs must be addressed and fulfilling these needs
requires a collaborative approach among patients, nurses, and other healthcare
professionals.
PMID- 11013903
TI - Current treatment approaches for neoplastic meningitis: nursing management of
patients receiving intrathecal DepoCyt.
AB - PURPOSE/OBJECTIVES: To review neoplastic meningitis and the nursing implications
for the intrathecal administration of chemotherapy. DATA SOURCES: Published
research and educational manuscripts, books, conference proceedings, and personal
experience. DATA SYNTHESIS: Standard treatment for neoplastic meningitis includes
radiotherapy to the neuraxis to palliate symptomatic disease, intrathecal
chemotherapy to eradicate cancer cells in the cerebrospinal axis, and systemic
chemotherapy. Intrathecal liposomal cytarabine (DepoCyt), a novel lipid
encapsulated chemotherapeutic agent, prolongs tumor exposure to cytotoxic levels
of cytarabine, improves patient response rates, and prolongs time to clinical
progression. CONCLUSIONS: DepoCyt prolongs the half-life of cytarabine in the
central nervous system, resulting in improved patient response to therapy and
delayed disease progression. IMPLICATIONS FOR NURSING PRACTICE: The clinical
success of DepoCyt treatment depends on effective implementation of the treatment
regimen, attentiveness to patient and family education, and adverse-event
management.
PMID- 11013904
TI - An international feasibility study of parental decision making in pediatric
oncology.
AB - PURPOSE/OBJECTIVES: To describe parental decision making about treatment options
for children with cancer and determine the feasibility of a similar but larger
international study. DESIGN: Exploratory. SETTINGS: A pediatric catastrophic
illness research hospital in the United States and children's hospitals in
Australia and Hong Kong. SAMPLE: A convenience sample of 43 parents (5 fathers
and 38 mothers ages 23-59 years). METHODS: Six open-ended interview questions
posed to parents during private individual interviews. Content analysis
techniques were used. MAIN RESEARCH VARIABLES: Parental perceptions of (a)
factors considered in the decision-making process, (b) behaviors of healthcare
professionals that affected the process, and (c) satisfaction with the process.
Feasibility of a larger study was estimated by considering ease of access to
parents, number of refusals to participate, understanding of the interview
questions, and level of interest at each setting. FINDINGS: Access to parents was
possible at all sites. Refusal to participate was reported only at the U.S. site.
Certain factors (e.g., getting information from the healthcare team, trusting
staff) were important to all parents considering end-of-life decisions. Site
specific factors included considering alternative therapies (at the Australian
site) and strengthening faith (at the U.S. site). CONCLUSIONS: A larger
international study of parental decision making is feasible. Sufficient
similarities in parental decision making exist across these sites to justify
future efforts to identify universal decision-making factors that, in conjunction
with site-specific differences, could be helpful in developing guidelines for
healthcare professionals who assist parents in making treatment-related decisions
for a sick child.
PMID- 11013906
TI - Men's perspectives on the impact of prostate cancer: implications for oncology
nurses.
AB - PURPOSE/OBJECTIVES: To describe the perspectives of men with recurrent prostate
cancer regarding their experiences with the disease, its impact, and the help
they received and to compare these individuals to men without recurrent prostate
cancer. DESIGN: Cross-sectional survey. SETTING: Physicians' offices and prostate
cancer self-help groups in Canada. SAMPLE: A convenience sample of 120 men with
recurrent prostate cancer and 845 men without recurrent disease. METHODS: A
survey instrument was developed following in-depth interviews with men living
with prostate cancer. The men received survey packages from their physicians or
through a self-help group, completed the instrument at home, and returned it in a
prestamped addressed envelope. MAIN RESEARCH VARIABLES: Impact on lifestyle,
satisfaction with communication, importance of information, satisfaction with
information received, problems experienced, and assistance received for problems.
FINDINGS: Significant differences related to a number of factors were found
between the men with recurrent prostate cancer and those without recurrent
disease. A large number of those with recurrent disease experienced problems with
side effects, anger, and pain and received help for their pain; experienced a
negative impact on leisure time and on mental health; experienced difficulty
talking with healthcare professionals; and felt the need to talk with someone
about their cancer. Many of the men with recurrent disease were dissatisfied with
the information they received about their medical condition and possible side
effects. CONCLUSIONS: Men with prostate cancer experience both physical and
psychosocial difficulties. Many perceive that they are not receiving adequate
help for these difficulties. Future research is needed to increase understanding
of how men are managing the impact of prostate cancer and what types of
interventions would be most useful. IMPLICATIONS FOR NURSING PRACTICE: Findings
emphasize the need for nurses to be certain that they are conducting broad-based
assessments of patients with prostate cancer throughout the illness experience.
Nurses need to inform patients about services available to assist them, help
patients understand the emotional responses to illness, and provide opportunities
for patients to talk about the illness and its impact.
PMID- 11013905
TI - Implementing the Agency for Health Care Policy and Research's Smoking Cessation
Guideline in a lung cancer surgery clinic.
AB - PURPOSE/OBJECTIVES: To determine the effectiveness of a nurse-managed smoking
cessation intervention based on the Agency for Health Care Policy and Research's
(AHCPR's) Smoking Cessation Guideline in a lung cancer surgery clinic. DESIGN:
Quasi-experimental. SETTING: Urban, Midwest, academic, and tertiary care. SAMPLE:
25 adult male and female smokers with a confirmed diagnosis of lung cancer that
had been surgically managed. Subjects were assigned to an intervention group (n =
14) or a usual-care group (n = 11). METHODS: Participants in the intervention
group received a nurse-delivered, AHCPR-based smoking cessation intervention that
included face-to-face and phone follow-up contact beginning with the first
preoperative clinic consultation. Usual-care participants received routine care
provided at the institution. MAIN RESEARCH VARIABLES: Self-reported smoking
status with expired air carbon monoxide confirmation six months postsurgery.
FINDINGS: Seventy-one percent of the intervention group was biochemically
confirmed to be abstinent by expired air carbon monoxide, as compared to 55% in
the usual-care group. CONCLUSIONS: Smokers diagnosed with lung cancer desired to
quit smoking and may benefit from an intensive smoking cessation intervention at
time of diagnosis. IMPLICATIONS FOR NURSING PRACTICE: Further research should
include continuing evaluation of an intensive smoking cessation intervention with
this population, and all clinicians should be trained to implement AHCPR's
Smoking Cessation Guideline in practice.
PMID- 11013907
TI - Exploring the information flow: partners of women with breast cancer, patients,
and healthcare professionals.
AB - PURPOSE/OBJECTIVES: To explore the information flow between partners of women
with breast cancer and patients and between partners and healthcare professionals
(HCPs). DESIGN: Descriptive. SETTING: Community-based. SAMPLE: 109 partners of
women with breast cancer. METHODS: Subjects completed a 30-item, self
administered questionnaire that was designed to identify the informational flow
between them and their information providers. Subjects also completed the Miller
Behavioral Style Scale to determine the informational coping styles of
individuals under threat. MAIN RESEARCH VARIABLE: Informational flow between
partners and patients and partners and HCPs. FINDINGS: The majority of partners
received information from patients and were satisfied with the amount of time
they spent discussing breast cancer topics. Few partners thought that patients
avoided giving them information. A significant association existed between the
informational coping styles of partners and the communication flow between
partners and patients. The majority of partners sought information from other
sources. In addition, the majority of partners accompanied patients to their
medical consultations and received information from HCPs. The communication flow
among partners, patients, and HCPs largely depended on the amount of
communication desired by the woman with breast cancer. CONCLUSIONS: This study
provides new evidence on the information flow and communication patterns between
partners and patients and between partners and HCPs. IMPLICATIONS FOR NURSING
PRACTICE: Partners may have informational needs that are not met by patients.
Therefore, nurses need to provide them with information to help satisfy their
needs. In addition, nurses can help satisfy the informational needs of partners
by encouraging good two-way communication and informational exchange between
partners and patients.
PMID- 11013908
TI - Assessment of patient satisfaction with pain management in small community
inpatient and outpatient settings.
AB - PURPOSE/OBJECTIVES: To describe patient outcomes (e.g., pain intensity and
relief, satisfaction, expectations) and analgesic practices of healthcare
providers for inpatients and outpatients in community hospital settings. DESIGN:
Descriptive, correlational, and random sampling. SETTING: Three community-based
institutions in southeast Louisiana. SAMPLE: 114 inpatients and outpatients with
cancer-related or acute postoperative pain. Inpatients (n = 68) mostly were women
and younger than 60 years of age. Outpatients (n = 46) mostly were men and older
than 60 years of age. Both groups were predominantly well-educated and Caucasian.
METHODS: Subjects completed a modified version of the American Pain Society's
Patient Satisfaction Survey. Researchers completed a chart audit tool reviewing
analgesic prescriptive and administrative practices. FINDINGS: Weak to moderately
strong correlations existed for the relationships between the satisfaction
variables and the pain intensity, pain relief, and expectation variables for all
subjects. Satisfaction with current pain intensity was correlated most strongly
with pain intensity and relief scores. Higher pain intensity and relief were
related to lower satisfaction with current pain intensity. CONCLUSIONS:
Regardless of setting or pain type, subjects experienced significant amounts of
pain during a 24-hour period. Patient expectations for experiencing high levels
of pain were realized, but expectations for significant pain relief were not.
IMPLICATIONS FOR NURSING PRACTICE: Institutional pain management programs that
approach pain from a multidimensional perspective need to be developed. Continued
education for healthcare professionals and patients is a vital part of this
process.
PMID- 11013909
TI - [The right way to the future of knee endoprostheses].
PMID- 11013910
TI - [Orthopedics, orthopedic surgery, trauma surgery. Coming full circle?!].
PMID- 11013911
TI - [Knee endoprostheses: problems and technological developments from the
manufacturer's point of view].
AB - Modern-day knee arthroplasty is based principally on the experience gained in the
course of the past three decades. In the 1980s and 1990s, for example, the full
constraint models of the 1970s were replaced by surface replacement prostheses
with a combined rolling/sliding motion approximating the natural motion of the
human knee joint for a wide range of applications. Not all of the relevant
questions in the areas of material science, biomechanics, tribology, implant
fixation and surgical technique have been fully explored by any means.
Nevertheless, the medium-term and long-term results presently attained by knee
arthroplasty are comparable to those achieved in the field of hip-joint
arthroplasty. Although the success achieved by today's knee-joint prostheses is
impressive, a critical analysis of therapeutic failures and complications is
necessary to discover areas where further research is necessary and to formulate
the challenges presenting themselves in R&D and in the manufacture of artificial
knee joints. Currently, research efforts are focused on optimizing materials
(especially in light of the presently unsatisfactory wear behavior of artificial
knee joints), biomechanically-assisted design optimization to achieve a better
harmonization between mobility and stability in the knee joint to be treated,
alternative anchoring concepts, including consistently cement-free anchoring, and
solutions for simplifying implantation techniques and making them more precise.
The latter area, in particular, appears to be of great importance, since the
quality of artificial knee joints and the long-term therapeutic outcome of knee
joint arthroplasty depend to a great extent on the correct alignment of the leg
axes, an optimal implant position, and the correct adjustment of soft tissue
tension. Technical innovations in this area of implant technology exert a
multifactorial impact on different aspects of arthroplasty--e.g., uniform force
transfer to minimize wear, selective rotation of the femoral components to
optimize patella tracking, and avoidance of load concentrations to improve
fixation strength--and thus form the basis for a surgical approach that takes
greater account of "the big picture". Today's sophisticated navigation systems
are a case in point. The non-imaging systems, in particular, have proved to be
exceptionally useful; their advantages lie in their simple handling which makes
use of common surgical techniques, the avoidance of additional imaging data
recording (e.g. CT images), and an inconsequential increase in operation times.
PMID- 11013912
TI - [Knee endoprosthesis: aspects of surgical techniques].
AB - The implantation of a condylar knee has remained a challenge for surgeons and the
equipment of the hospital. In contrast to total hip arthroplasty, not only is the
correct insertion of the implant crucial, but also the treatment of the
surrounding soft tissues. Mediolateral soft tissue balance and balance between
flexion and extension gaps, as well as centering the patella, have to be done
carefully. The soft tissue envelope of the knee joint is thin and prone to
necrosis after multiple incisions. Damage to the extension mechanism can make a
total joint useless. Tearing the patellar ligament from the tibial tuberosity
must therefore be avoided by all means during operation. Precise cutting of the
distal femur is only possible if excellent equipment is used by a skillful
surgeon. The same is true for orientating saw cuts related to the long leg axes.
These tasks can probably be taken over by navigation systems and robots in the
future. Because the definite choice of implants has to be made intraoperatively,
a complete modular system has to be present in the hospital. Only hospitals that
can properly equip their surgeons to manage upcoming soft tissue problems and
bony deficiencies should offer treatment to patients requiring condylar knee
arthroplasty.
PMID- 11013913
TI - [Knee endoprosthetic surgery: tasks and problems of the surgical instrument
teams].
AB - About 220 knee endoprostheses are implanted at our clinic annually. This is a
routine procedure for the instrument staff. Practice has shown, however, that
deficient operating room management as regards the instruments, implants,
operating room staff, and surgical planning causes problems. As a result of this,
a prophylactic search for sources of error began (risk management). If the
sources of error are found, described, and remedied, knee endoprosthetic surgery
will be successful for both the patient and the surgical team. Cooperation and
communication among manufacturer, surgeon, and surgical nursing staff should
serve to minimize forensic risks. The most important task of the instrument staff
is to produce adequate structure and procedural quality so that a positive result
can be achieved.
PMID- 11013914
TI - [Knee endoprosthesis: anesthesiological considerations].
AB - The anesthetic care of patients undergoing total knee arthroplasty (TKA) is
described based on experience with reports of the recent literature. The problems
and complications of cooperation between different personnel and speciality
groups treating the patient are of a more organizational nature during the
preoperative phase, and are aimed primarily at determining the appropriate
scheduling of the operation. At the forefront intraoperatively is the appropriate
monitoring of the patient, and the adjustment of anesthetic regimes to the
individual needs and requirements of the patient. The obligation for intensive
monitoring as well as an appropriate pain therapy are indispensable in the
postoperative phase.
PMID- 11013915
TI - [Knee endoprosthesis: biomechanical requirements and consequences].
AB - The experiments described herein permitted the dynamic in vitro measurement of
the mechanical efficiency of the quadriceps muscle, both before and after total
knee arthroplasty (TKA). The measurement of tibiofemoral pressure on fixed and
mobile polyethylene inlays, as well as the movement of mobile inlays, is
described. The Interax TKA system was implanted in 8 fresh frozen knee cadavers
which were then mounted onto a knee-simulating machine. An isokinetic extension
motion was simulated by extending the knee specimens under a constant extension
torque of 31 Nm. The quadriceps muscle force required for this motion was not
found to increase after implantation of the prostheses. Pressure on the mobile
inlay was 60% lower than that measured on the fixed inlay. A 4-mm posterior
migration of the mobile inlay on the tibial base plate was observed, with no
motion of the inlay femoral component contact surface, which migrated posteriorly
in the fixed bearing prosthesis. Thus, instead of moving posteriorly, the mobile
inlay femoral component contact area remained at the center of the inlay during
the entire extension motion.
PMID- 11013916
TI - [Knee endoprosthesis: selection and requirements of materials].
AB - The possibilities of using different material combinations for the replacement of
knee joint endoprostheses are very limited. Therefore, cobalt-chromium-molybdenum
alloys are currently being used for femoral components and ultra-high molecular
weight polyethylene for tribologically stressed tibial components. Titanium
alloys can be considered for the tibial component only. For tribological reasons,
it is not possible to use a femoral component made of titanium unless it has a
corresponding coating. As far as the design is concerned, problems arise from the
fact that, on the one hand, there is a demand for the smallest possible size or
resection height. On the other hand, however, the forces and strains are rather
high and therefore a certain material thickness is necessary in order to avoid
fatigue fracture. Regarding polyethylene, the same known principle must be taken
into consideration here--not to avoid using the so-called floating design, i.e.,
the polyethylene components should always have a supporting limitation, or cold
flow might occur. The tribological behaviour of polyethylene is restricted in
cases of constrained tibia plateaus in so far as the linear or punctual contact
of the initial run-in phase leads to correspondingly high surface pressure
consequently overstressing the polyethylene. In order to improve this, mobile
meniscal bearings are used and the surface pressures achieved here can be endured
by the polyethylene even over a long-term. The extent to which the new so-called
cross-linked polyethylene can be used in knee joint endoprosthetics is currently
being tested, and the simulator results in this respect have been promising so
far.
PMID- 11013917
TI - [Knee endoprosthesis: clinical aspects].
AB - Despite improvements in component design, instruments, and operative technique,
there remains a significant complication and failure rate in total knee
arthroplasty (TKA). Revision TKA accounts for every tenth operation in TKA. From
June 1991 to June 1994, 209 TKAs (182 patients) were performed. Of these, 73%
were uncemented, 11.2% cemented, and 15.8% hybrid. The patella was resurfaced in
96% with a cemented polyethylene or an uncemented metal-backed patella component.
Follow-up showed significant improvement in knee and function scores 1 and 5-7
years postoperatively. Of the patients, 77% showed no general and 80% no local
postoperative complications. Overall, 42 revisions (41 patients) were performed
during the 7-year follow-up. Revision surgery was necessary because of aseptic
loosening (8.1%), polyethylene wear (4.8%), complications of the extensor
mechanism (2.4%), traumatic periprosthetic fractures or knee luxation (1.4%), and
septic loosening (3.3%). Further improvements of polyethylene will reduce
polyethylene wear. Uncemented fixation of this prosthesis can only be recommended
with hydroxyapatite coating.
PMID- 11013918
TI - [Knee endoprosthesis: sports orthopedics possibilities and limitations].
AB - Many patients would like to resume some sport activities after total knee
replacement; however, most recommendations are based on subjective opinion rather
than scientific evidence. The following paper presents a literature review of
sports after total knee replacement and includes recommendations which are based
on biomechanical laws. Most total knee designs show increased conformity near
full extension. Beyond a certain knee flexion angle, the conformity ratio
decreases due to a reduced femoral radius. Therefore, these designs accept higher
loads near full extension than in flexion. In order to recommend suitable
physical activities after total knee replacement, both the load and the knee
flexion angle of the peak load must be considered. It has been shown that power
walking and cycling produce the lowest polyethylene inlay stress of a total knee
replacement and seem to be the least demanding endurance activities. Jogging and
downhill walking show high inlay stress levels and should be avoided. Hence, for
mountain hiking, patients are advised to avoid descents or at least use skipoles
and walk slowly downhill to reduce the load on the knee joint. It must also be
mentioned that any activity represents additional wear, which may affect the long
term results of total knee replacements. Further clinical studies are necessary
to validate the biomechanical investigations.
PMID- 11013919
TI - [The 48th Annual Meeting of the Society of South Germany Orthopedists, Baden
Baden, 28 April-1 May 2000].
PMID- 11013920
TI - Experiences in the realisation of a research project on anthroposophical medicine
in patients with advanced cancer.
AB - QUESTIONS UNDER STUDY: To date most of the published studies on the effectiveness
of complementary therapies in cancer patients have yielded controversial results
because of questionable methodology. Research strategies and methodologies
acceptable to both conventional and unconventional medicine are difficult to find
due to different belief systems. In this publication we describe the development
and implementation of a project conducted as part of National Research Programme
34 (NFP 34). Detailed analysis of our experiences might provide some information
on how to deal with practical difficulties in the planning and conduct of further
research projects in this field. The project involved the anthroposophical Lukas
Clinic in Arlesheim and the Institute of Medical Oncology of the University
Hospital, Berne. This interdisciplinary research project was devised to study the
relative merits of these two schools of medicine in the care of advanced cancer
patients. The project was made up of three components: (1) a registration study
aimed at comparing the case mix at the two institutions; (2) a three armed
randomised study on the effectiveness of supportive therapy, comparing
anthroposophy to psychosocial group therapy, and (3) a longitudinal study to
monitor the evaluation of quality of life of patients at the anthroposophical
clinic. METHODS: After a brief review of the study protocol, which presents the
theoretical framework of the project, problems of its implementation are
described. Aspects of accrual, acceptance of randomisation and data availability
are presented using simple descriptive statistics and logistic regression.
RESULTS: The registration study was duly completed with a total of 567 patients.
For several reasons (not meeting inclusion requirements, high refusal rate) the
accrual into the randomised study was slower than expected and required
modification of the original design specifications with regard to inclusion
criteria and data collection schedule. Additionally, a high dropout rate
contributed to premature closure of this part of the project. The longitudinal
study also suffered from low data availability at follow up. CONCLUSIONS: The
study protocol constituted a major effort at compromise without loss of
scientific rigour, and this effort demonstrates that it is possible to allow for
different views on patients, on clinical interventions and on research strategies
when establishing collaboration between different schools of medicine. Despite a
theoretically sound framework, the randomised part of the project proved
difficult in its practical execution. Some unexpected logistical constraints and
some unmet expectations influenced the feasibility of this part of the project.
Therefore, careful planning of research projects in this field of medicine should
always include an extended analysis of various practical aspects of study
implementation.
PMID- 11013921
TI - Clinical features and analysis of the duration of colonisation during an outbreak
of Salmonella braenderup gastroenteritis.
AB - During an outbreak of acute Salmonella braenderup gastroenteritis we performed a
standardised interview encompassing questions on clinical symptoms in 156 (127
adults and 29 children) of 215 identified patients. Sequential stool cultures
were obtained for up to five months in these 156 cases. We restricted the
analysis to the 122 patients with at least 3 or more available cultures. They
were treated with a fluoroquinolone, trimethoprim-sulfamethoxazole, or not
treated with antibiotics, according to the decision of the practitioners. For
this reason, a randomised double blind study was not possible. Minimum inhibitory
concentrations (MIC) of the prescribed drugs were measured for representative
isolates before and after treatment. The most frequent symptoms were diarrhoea
(98%) and abdominal pain (96%). Vomiting occurred in 43% of cases. Children were
more severely ill. Seven weeks after acute gastroenteritis, stool cultures were
still positive for salmonella in 71% of the 22 children and 30% of the 100 adults
examined (p < 0.002). This rate decreased progressively in both groups to 5 and
3% respectively at 20 weeks (n.s.). Among adults, no significant difference in
enteric carriage over time could be demonstrated between untreated patients and
those treated with either a fluoroquinolone or trimethoprim-sulfamethoxazole. MIC
for salmonella isolates remained unchanged after treatment. In a cohort of
patients infected with a single strain of salmonella, fluoroquinolone therapy of
acute gastroenteritis failed to influence the duration of enteric carriage,
despite continuing susceptibility of the strain. In children, the rate of
clearance of Salmonella braenderup from stool was statistically lower until the
tenth week after the acute disease, but there was no further difference after 5
months.
PMID- 11013922
TI - [Medical treatment of heart failure: an analysis of actual treatment practices in
outpatients in Switzerland. The Swiss "IMPROVEMENT of HF" Group].
AB - BACKGROUND: From several studies in Europe and the USA there is evidence that
drug treatment of patients with congestive heart failure (CHF) could be improved.
There are only sparse data on the treatment of this population in Switzerland.
METHODS: In the context of a European Study (IMPROVEMENT of HF Study), in 1999,
the treatment of 474 patients with symptomatic CHF was recorded by chart review
with primary care physicians throughout Switzerland. The effect of potential
predictors of drug treatment was tested using multivariate logistic regression.
RESULTS: Mean age of the study population was 75 +/- 12 years. Overall,
angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor
blockers (ARB) were prescribed to 65% of the study population. Beta-blockers,
loop diuretics/thiazides, spironolactone and digitalis were prescribed to 25%,
73%, 13% and 31% respectively. Compared with CHF patients < 65 years of age, the
odds ratio of ACE-I/ARB prescription in patients aged 65-74, 75-84, and > or = 85
years was 0.80, 0.58 and 0.40 respectively (p < 0.001). The respective odds
ratios for beta blocker treatment were 0.37, 0.21 and 0.06 (p < 0.001). In
addition, NYHA classification, comorbid conditions such as renal failure and
contraindications strongly predicted drug prescription. Gender and geographical
area were not associated with drug selection. CONCLUSIONS: Overall drug
prescription among CHF patients in Swiss primary care appears to be satisfactory.
However, prescription of ACE-I/ARB and beta-blockers falls steeply with
increasing age, independent of measured comorbid conditions and
contraindications. Thus, improvement of treatment should focus on a more
consistent use of these drugs in the segment of elderly CHF patients.
PMID- 11013923
TI - [Start of an adult living donor liver transplantation program in Switzerland].
AB - The shortage of cadaver organs has prompted transplant centres to seek new
sources of grafts. While living-donor left lobe transplantation (segments II and
III) is an established procedure for children, living donor right liver
transplantation (segments V, VI, VII, VIII), which can provide adequate liver
mass for an average-sized adult patient, is technically more demanding and
potentially associated with higher risks for the donor. In view of the permanent
shortage of organs in Switzerland, we started an adult living donor liver
transplantation programme in 1999 with the approval of the Clinical Ethics
Committee of Geneva University Hospitals. Donor evaluation was performed only
after the recipient had been officially registered for transplantation in the
national waiting list. Preoperative evaluation consisted of a preliminary
information phase with blood tests and Doppler ultrasonography, a second phase
with radiological non invasive investigations (CT scan with volume measurements,
magnetic resonance cholangiography) and a third phase including liver biopsy and
angiography. A formal psychiatric evaluation was performed in all cases and
detailed consent was required. Eight potential donors were investigated, 5 were
not retained because of too small right liver or steatosis, and 3 were accepted
(wife, son, sister). Living-donor hepatectomy was performed without interrupting
the vascular blood flow. The liver graft was perfused ex-situ with University of
Wisconsin solution. The grafts were anastomosed to the preserved vena cava of the
recipient and the portal and arterial anastomoses were performed without
interposition grafts, with short cold ischaemic times in the 3 cases. The graft
to-recipient weight ratio ranged from 1.04 to 1.12%. The grafts worked
immediately; the post-operative course in the 3 recipients was unremarkable and
no rejection episode occurred. Significant complications were observed in one
donor (percutaneously drained bilioma and spontaneously resolved popliteal
sensory palsy). Living-donor right liver transplantation is a potentially
valuable solution to the increasing shortage of donor organs. The procedure can
be performed safely provided stringent criteria for donor selection, for donor
recipient coupling (> 1% graft to body weight ratio) and for centre selection
(experience in liver surgery, reduced and split liver transplantation) are
applied.
PMID- 11013924
TI - [Expandable esophageal stent for the treatment of esophageal fistula].
PMID- 11013925
TI - [Long-term results after successful mitral valvuloplasty: comparison of Inoue and
double balloon technique].
AB - Mitral balloon valvuloplasty is the treatment of choice for severe mitral
stenosis in young patients with a minimally calcified and pliable mitral valve.
The present study reports the results of the first 65 patients undergoing mitral
valvuloplasty in Zurich with the double-balloon or Inoue-balloon technique. Early
outcome and late follow-up over 4.1 +/- 2.5 years were evaluated in these
patients. PATIENTS: Percutaneous mitral valvuloplasty was performed in 65
patients (48 females and 12 males, mean age 41 +/- 11 years). The double-balloon
technique was used in 25 and the Inoue-balloon technique in 40 patients. Left
ventricular pressure as well as pressure gradient and valve area were calculated
before and after the intervention. Mitral valvuloplasty was considered to be
successful when the valve area was > or = 1.5 cm2 and the pressure gradient < or
= 8 mm Hg. RESULTS: Mitral valvuloplasty was successful in 22 patients of group 1
and 39 patients of group 2. Acute complications were observed in 4 patients (6%),
i.e. 1 perforation of the left atrium, 1 perforation of the left ventricle, 1
peripheral embolisation and 1 rupture of the mitral leaflet. Mitral valve area
increased from 1.0 to 1.9 cm2 with the double-balloon and from 1.0 to 2.0 cm2
with the Inoue-balloon technique. The pressure gradient over the mitral valve
dropped significantly from 11 to 4 mm Hg in group 1 and from 15 to 5 mm Hg in
group 2. Left ventricular ejection fraction remained unchanged but left atrial
pressure decreased significantly in the first group from 20 to 9 mm Hg and in the
second group from 22 to 12 mm Hg. Long-term follow-up over 4.1 years showed a
mild (not significant) decrease in valve area from 1.7 to 1.6 cm2 in both groups,
with NYHA class unchanged and bicycle exercise capacity increased from 76 to 82%.
CONCLUSIONS: Mitral valvuloplasty with either the double-balloon or Inoue-balloon
technique provides excellent clinical, echocardiographic and haemodynamic
results. The long-term follow-up demonstrated a mild decrease in mitral valve
area but clinical symptomatology and physical exercise capacity remained
unchanged. From a technical standpoint the Inoue-balloon technique is easier to
use and has a lower complication rate (2.5%) compared to the double-balloon
technique (12%). Thus, in the last few years the double-balloon technique has
been replaced by the Inoue-balloon technique, with a good long-term outcome over
the first 4-5 years of follow-up.
PMID- 11013926
TI - [Controversies in the treatment of carotid stenosis].
PMID- 11013927
TI - [Carotid stenosis: epidemiology and symptomatology (see comment)].
AB - Risk factors for atherosclerotic carotid stenoses are smoking, arterial
hypertension, diabetes mellitus and hypercholesterolaemia. Atherosclerotic
carotid artery disease is a risk factor for the development of coronary artery
disease (CAD), and in older men the risk of CAD-related death is five times
higher than the risk of death related to ischaemic stroke. The prevalence of >
50% carotid stenoses in population-based studies in 6-11% for older men and 5-7%
in older women. Diagnosis and differential diagnosis of ischaemia-related
ophthalmologic and neurological deficits in the territory of the carotid artery
are discussed.
PMID- 11013928
TI - [Imaging methods in the diagnosis of carotid stenosis: is angiography obsolete?].
AB - The aim of diagnosis is exact grading of carotid stenosis. The existence of
different methods of measuring stenosis causes problems. Also, measurement of
stenosis using Doppler ultrasound is based on a wholly different principle.
Investigative methods for measurement of stenosis are selective angiography, CT
angiography, MR angiography and duplex Doppler ultrasound. On the basis of the
literature on the advantages and drawbacks, risks and accuracy of the various
methods in symptomatic patients, ultrasound is recommended as the primary
diagnostic tool. If Doppler ultrasound shows a stenosis of > 70%, MR angiography
or CT angiography is recommended. If the results correspond, no further
investigation is needed before surgery. If they do not correspond a selective
carotid angiogram is required. Sonographic diagnosis of carotid occlusion needs
confirmation by MR angiogram or CT angiogram.
PMID- 11013930
TI - [Amyloidoma].
PMID- 11013929
TI - [When is interventional therapy necessary for carotid stenosis?].
AB - Stenoses of the internal carotid artery are common. 20-30% of ischaemic
cerebrovascular events are due to atherosclerotic lesions of carotid arteries.
For many years endarterectomy has been a method for prevention of cerebral
ischaemia. There is confusion about how carotid stenosis should be measured on
angiograms. Since the results of clinical trials based on different measurement
methods are applied to routine clinical practice, the various measurement methods
must be comparable. We must know which one was used, and how to convert them by a
simple arithmetical equation. Carotid endarterectomy appears to be highly
beneficial in patients with recent hemispheric transient ischaemic attacks or non
disabling stroke and ipsilateral high-grade stenosis (> or = 60-70%) of the
internal carotid artery. Even asymptomatic patients with high-grade stenosis
benefit to some extent from surgery, and the beneficial effects correlate
directly with the degree of stenosis. Endarterectomy in moderate symptomatic
stenosis (50-69%) yields only a moderate reduction in stroke risk. In stenosis <
50% there is no benefit. Decisions about endarterectomy should take into account
the natural history of stroke in carotid stenosis, surgical skills, and the
individual patient's risk factors.
PMID- 11013932
TI - [In Process Citation]
PMID- 11013931
TI - [In Process Citation]
PMID- 11013933
TI - [In Process Citation]
PMID- 11013934
TI - [In Process Citation]
PMID- 11013935
TI - [In Process Citation]
PMID- 11013936
TI - [In Process Citation]
PMID- 11013937
TI - [In Process Citation]
PMID- 11013938
TI - [In Process Citation]
PMID- 11013939
TI - [In Process Citation]
PMID- 11013940
TI - [In Process Citation]
PMID- 11013941
TI - [In Process Citation]
PMID- 11013943
TI - [In Process Citation]
PMID- 11013942
TI - [In Process Citation]
PMID- 11013944
TI - [In Process Citation]
PMID- 11013945
TI - [In Process Citation]
PMID- 11013946
TI - [In Process Citation]
PMID- 11013947
TI - [In Process Citation]
PMID- 11013948
TI - [In Process Citation]
PMID- 11013949
TI - [In Process Citation]
PMID- 11013950
TI - [In Process Citation]
PMID- 11013951
TI - [In Process Citation]
PMID- 11013952
TI - [In Process Citation]
PMID- 11013954
TI - [In Process Citation]
PMID- 11013953
TI - [In Process Citation]
PMID- 11013955
TI - [In Process Citation]
PMID- 11013956
TI - [In Process Citation]
PMID- 11013958
TI - [In Process Citation]
PMID- 11013957
TI - [In Process Citation]
PMID- 11013959
TI - [In Process Citation]
PMID- 11013960
TI - Distinguishing B and T lymphocytes by scanning electron microscopy.
AB - This work demonstrates differences between B lymphocytes and T lymphocytes as
seen in the scanning electron microscope (SEM). Slides of routinely prepared
benign and malignant lymphoid tissues were viewed in the SEM. The location of
prominent populations of T lymphocytes and B lymphocytes was verified by
immunocytochemical staining respectively with CD3 and CD20 antisera. Benign
tissues, including infant thymus and adult hyperplastic lymph node, were compared
with malignant lymphomas of T-cell and B-cell types. The SEM appearance of benign
B and T lymphocytes is compared utilizing the backscattered electron (BSE) mode
and secondary electron (SE) mode in adult hyperplastic lymph node and infant
thymus, respectively. The BSE and SE modes reveal that the sectioned T-lymphocyte
nucleus has a more complex configuration than that of the B lymphocyte. T
lymphocytes appear more discrete and separated one from another, while B
lymphocytes exhibit close cellular association to form a syncytial array. These
features are noted also in malignant lymphomas of B-lymphocyte and T-lymphocyte
types, respectively. The SEM can distinguish between B and T lymphocytes by
studying the differences in nuclear and chiefly the cell to cell appearances. The
syncytial configuration of B lymphocytes may reflect prominent expression of cell
adhesion molecules, e.g., ICAM-1, as noted in the literature.
PMID- 11013961
TI - Scanning electron microscopy of the interior of cells in Hurthle cell tumors.
AB - Four cases of Hurthle cell tumor were examined by scanning electron microscopy
after being macerated to remove all soluble components. By all morphological
criteria, Hurthle cells are oncocytes with their usual augmented complement of
mitochondria. The Hurthle cell mitochondria either are ovate with central stacks
of cristae or elliptical or rod-like with cristae that often are finger-like. As
in salivary gland oncocytes, the shelf-like cristae are anchored to the inner
boundary membrane by tubular necks. In some Hurthle cells, all of the
mitochondria exhibit reticulate cristae. A few mitochondria harbor a globular
inclusion in their inner compartment. The Golgi apparatuses are relatively
simple, consisting of imbricated saccules that are edged by small, bud-like
structures. The rare lumina in the midst of clusters of Hurthle cells are lined
by numerous microvilli. Thus, scanning electron microscopy of macerated Hurthle
cell tumors has revealed a number of features, especially of their mitochondria,
that have escaped detection by transmission electron microscopy.
PMID- 11013962
TI - Clinical, biochemical, and pathological features in a patient with plasma cell
dyscrasia and Fanconi syndrome.
AB - Multiple myeloma is associated with a wide array of renal diseases that include
myeloma cast nephropathy, monoclonal immunoglobulin deposition disease,
amyloidosis, cryoglobulinemia, tubular dysfunction, pyelonephritis,
nephrocalcinosis, urate nephropathy, and infiltration by atypical plasma cells
(or myeloma cells). Filtered immunoglobulin light chains may affect both the
distal and, more frequently, the proximal tubule. Tubular abnormalities in
patients with plasma cell dyscrasia may be more frequent than previously thought.
A patient with a plasma cell dyscrasia is described, who presented with
biochemical features consistent with Fanconi syndrome. Immunoelectron microscopy
performed on the renal biopsy confirmed the presence of kappa light chain
immunoglobulin in intracytoplasmic crystals in proximal tubular epithelial cells.
This report is one of a few demonstrating the presence of light-chain
immunoglobulin in intratubular crystals in a human renal biopsy obtained from a
patient with a plasma cell dyscrasia and Fanconi syndrome.
PMID- 11013963
TI - Acinar cell carcinoma of the pancreas.
AB - Four cases of acinar cell carcinoma of the pancreas are reported. An acinar cell
carcinoma can resemble an islet cell tumor by routine light microscopy but the
two differ considerably in their fine structure and immunostaining properties.
Although cells of both tumors contain numerous dense-core granules, their size
ranges are different, and atypical forms occur in the acinar cell tumors,
including elongated bodies filled with filaments. Many mitochondria-rough
endoplasmic reticulum complexes were present in one tumor. In a liver metastasis,
nests of endocrine cells were discovered amid the groups of acinar cells, and
some of the endocrine granules contained rectangular cores.
PMID- 11013964
TI - Malignant fibrous histiocytoma: an ultrastructural perspective.
AB - Malignant fibrous histiocytoma is a frequent diagnosis, but the relationship of
the tumors to histologically similar soft tissue neoplasms is controversial. In
this study, 157 examples representing the 4 main subtypes were reviewed by light
microscopy and each tumor was studied with the electron microscope.
Immunohistochemical stains were performed on 77 tumors. Electron micrographs on
100 fibrosarcomas were reviewed for comparison. Malignant fibrous histiocytomas
often closely resemble fibrosarcomas at the ultrastructural level and differences
between the two are generally of degree only. Evidence for true histiocytic
differentiation was not found. The immunohistochemical results did not contradict
the authors' impression from electron microscopy that malignant fibrous
histiocytoma forms part of the histologic spectrum of tumors of fibroblasts.
PMID- 11013965
TI - The altered structure of renal papillary outflow tracts in obesity.
AB - Weight gain is associated with an expanded renal medullary interstitium in humans
and in animal models of obesity. In this study, the consequence of obesity and
this expanded matrix on renal papillary structure was examined in 15 obese
rabbits fed a high fat diet for 8-12 weeks compared to 21 rabbits fed a standard
diet. When examined under a dissecting microscope, the tips of the renal papillae
from formalin-fixed, methylene blue-stained kidneys showed patent ducts of
Bellini in 5 of 5 instances from 2 lean rabbits, but in only 2 out of 12 ducts
from 3 obese rabbits. The ostia of the remaining ducts were significantly
distended (205 +/- 42 microns versus 56 +/- 8 microns) and occupied by lightly
staining granular material. When examined with scanning electron microscopy, all
ducts were patent in lean rabbits (6 ducts in 4 rabbits, averaging 104 +/- 12
microns across), whereas only 6 of 11 ducts were patent in papillae from 4 obese
rabbits. Renal medullary parenchymal tissue appeared at the openings of the
remaining 5 ducts of Bellini in the 4 rabbits. Not only were these 5 ducts
significantly distended by the interstitial material (with openings averaging 248
+/- 56 microns across), but the associated collecting ducts were dilated relative
to control (100 +/- 15 microns versus 75 +/- 7 microns). Since the ducts of
Bellini are the only renal openings that are not corsetted by a fibrous capsule,
the authors speculate that the expanded medullary interstitium and increased
renal sinus lipid partially obstruct renal outflow and elevate renal interstitial
hydrostatic pressure in obesity, causing a prolapse of parenchymal contents,
further obstructing urine outflow and leading to distention of the collecting
ducts and ducts of Bellini.
PMID- 11013966
TI - Cytoplasmic changes in satellite cells of spinal ganglia induced by cisplatin
treatment in rats.
AB - The effects of cisplatin (cis-DDP) therapeutic treatment on the cytoplasmic
compartment of satellite cells (SC) of rat dorsal root ganglia (DRG) were
evaluated. Female Wistar rats were treated once a week with i.p. injection of cis
DDP (2 mg/kg) for 9 weeks. Morpho-quantitative changes of the cytoplasmatic
organelles in SC cytoplasm from L4-L6 DRG were determined at the electron
microscopic level. The quantitative changes in the lysosomal system components
called dense bodies (DB) and in the mithocondria were stereologically evaluated.
The data from SC were compared to those from the neurons. The cis-DDP treatment
induced a great increase in DB and mithocondria volume of SC. Furthermore, the SC
sheath showed an increase of the cytoplasmic lamellar expansions responsible of
the physical dissociation of SC sheath from the nerve cell body surface. The
comparative analysis from SC and neurons showed that the drug affected primarily
the SC, supporting the idea that SC could be the initial target of cis-DDP
molecule. The alterations of the anatomical relationships between SC and neurons
could modify the cell control on extracellular solutions, altering the functional
role barrier attributed to SC. It appears that not only the DRG neurons but also
and principally the SC were involved in the peripheral neuropathy mechanisms
caused typically from therapeutic cis-DDP administration.
PMID- 11013967
TI - Meningioma with granulofilamentous inclusions.
AB - The authors report a case of intracranial meningioma with granulofilamentous
inclusions. A 50-year-old man had right trigeminal neuralgia due to trigeminal
nerve compression by a petroclival tumor and received tumor resection.
Microscopically, tumor cells containing eccentric nuclei and intracytoplasmic
hyaline inclusions were arranged in sheets and whorls. The inclusions were
negative for periodic acid-Schiff reaction. No histological anaplasia was seen.
Immunohistochemistry showed epithelial membrane antigen reactivity on the
cytoplasmic membrane. Immunoreactivity for vimentin was recognized in cytoplasm
adjacent to inclusions. However, confocal laser microscopic study revealed
immunoreactivity for vimentin even inside some inclusions. Ultrastructurally,
interdigitation of cytoplasmic processes and desmosomes connecting adjacent cells
were noted. Inclusions were composed of numerous fine osmiophilic granules
attached by intermediates filaments. These findings were consistent with a
meningioma with the granulofilamentous inclusions described earlier. The findings
demonstrated by confocal laser microscopy and electron microscopy suggest that
these granular materials may be the metabolic products of vimentin filaments.
PMID- 11013968
TI - Apparent progression of acute glomerulonephritis to dense deposit disease.
AB - One week after the diagnosis of meningococcal meningitis, an 8-year-old boy
presented with acute renal failure and hypocomplementemia. A renal biopsy showed
"postinfectious glomerulonephritis" and acute tubular necrosis. Hematuria,
proteinuria, and low complement levels persisted, and 2 years later a follow-up
renal biopsy revealed dense deposit disease. The apparent progression of
postinfectious glomerulonephritis to dense deposit disease as observed in this
patient has not been previously described.
PMID- 11013969
TI - Cardiology and cost control: the ethical challenge for the new millennium.
AB - Government interventions in the health care sector threaten the traditional role
of physicians, since they are increasingly forced to consider the cost of medical
care when making decisions on behalf of their patients. To prepare themselves for
this ethical challenge and to actively participate in the debate about cost
containment, physicians need to understand how health economists and politicians
view the problem of rising medical costs. This review summarizes some essential
facts and findings of the health economics literature that provide the rationale
for different approaches to cost containment. The effects of rapidly growing
health care cost on the economy are discussed, and improvement of medical
technology is identified as the driving force behind this growth. The different
policy instruments, which can be employed for cost containment, are explained
against this background with an emphasis on Managed Care and global budgets. The
outlined concepts are finally discussed in the context of the current debate
about the proposed cost containment legislation in Germany.
PMID- 11013970
TI - [C-reactive protein as an independent marker of prognosis in acute coronary
syndrome: comparison with troponin T].
AB - BACKGROUND: It has been suggested that inflammatory processes play a role in the
pathogenesis of acute coronary syndromes (ACS). C-reactive protein (CRP) is a
classic acute phase protein. It is yet unclear whether, in addition to
established markers as troponin T (TnT), determination of CRP in patients
admitted for ACS contributes significantly to the diagnosis and prognosis of ACS.
PATIENTS AND METHODS: We investigated 50 patients with ACS (59.4 SD 13.9 years)
in the first hour after admission and 4-24 h later with respect to TnT (Elecsys,
Roche Diagnostics) and CRP (biokit, modified Quantex CRP plus, analytical
sensitivity 0.02 mg/dL). Fifty percent of the patients were classified as having
unstable angina retrospectively. All patients were followed in the 6 weeks post
discharge regarding death and recurrent ACS. RESULTS: The cumulative event rate
at 6 weeks after discharge was 62.5% for patients being CRP and TnT positive
compared to 35.3% in TnT positive and CRP negative patients. In TnT negative
patients a positive CRP test predicted 33.3% of events and 28.8% of patients
negative for CRP and TnT had events at 42 days post discharge. Logistic
regression analysis regarding the primary endpoint including TnT and CRP (4-24 h
values), age, gender and diagnosis resulted in independent prediction of ACS or
death by TnT (cutoff 0.1 microgram/L, p = 0.048, odds ratio = 7.5) and CRP
(cutoff 0.862 mg/dL, p = 0.026, odds ratio = 5.3). Sensitivity/specificity for
AMI diagnosis were 69.6%/75% for TnT and 12%/72% for CRP in the first hour and
91.3%/68.2% for TnT and 68%/72% for CRP 4-24 h later. CONCLUSIONS: Besides TnT,
high sensitivity CRP determination has no additional value for early AMI
diagnosis. The prognosis of these patients during the first 24 hours is
significantly and independently predicted by CRP measurements in addition to
troponin T.
PMID- 11013971
TI - [Risk stratification in heart surgery: do risk scores facilitate the
determination of indications?].
AB - Various risk scores have been developed for the assessment of operative risk in
cardiac surgery. Although risk stratification has been acknowledged as a useful
tool to analyze trends in therapy and changes in patient populations, its
relevance in assessing the indication for surgery has been questioned. It was the
goal of this prospective study to compare 6 common risk scores with regard to the
predictive value for mortality in individual patients. Between September 1998 and
February 1999 all adult patients undergoing heart surgery were prospectively
scored according to the following scores: initial Parsonnet, Cleveland Clinic,
French, Euro, Pons, and the Ontario Province Risk score. Early lethality was
assessed within 30 days postoperatively. Follow-up was completed in 504 patients.
With the exception of the Ontario Province Risk score, lethality in the high risk
group was overestimated by all scores, whereas lethality in low to moderate risk
groups was underestimated by several scores. Mean scores of surviving and
deceased patients showed a broad overlap with high standard deviations.
Preoperative risk scores are effective tools for stratification of patient
populations and the analysis of surgical outcome. With the aid of risk scores,
operative risk can be sufficiently predicted for patient populations or
subpopulations. The Euro score best predicted the outcome of our patients.
However, when the indication for surgery is to be determined in an individual
patient, risk scores should be only considered as an orientation in the decision
process.
PMID- 11013972
TI - [Restenosis predictors after stent implantation of venous aortocoronary bypass
grafts].
AB - Follow-up studies after stent implantation of native coronary arteries have
reported reduced rates of angiographic restenosis. In contrast, stent
implantation in the treatment of obstructive disease of coronary artery bypass
grafts is complicated by higher restenosis rates. We sought to determine, if
different predictors contribute to the high restenosis rate following stent
implantation of coronary artery bypass grafts. We investigated long-term
angiographic outcome of 205 stent implantations performed in 177 patients.
Multivariate analysis correlated clinical, procedural and angiographic variables
with the incidence of angiographic restenosis defined as diameter stenosis > 50%
at follow-up. Angiographic restenosis was observed in 34% of lesions treated.
Multiple logistic regression analysis defined diabetes mellitus (OR 6.89, CI 2.41
9.69), graft recanalization (OR 2.69, CI 1.08-6.63), lesion at the aortic
anastomosis (OR 6.98, CI 2.76-19.25), lesion at the coronary anastomosis (OR
2.95, CI 1.18-7.49), high diameter stenosis after stent placement (OR 7.01, CI
2.64-15.71), placement of long stents (OR 2.78, CI 1.11-7.36) and implantation of
more than one stent (OR 7.34, CI 2.08-20.15) as independent predictors of graft
in-stent restenosis. Critical consideration of these variables may help to
identify patients who are poor candidates for stent implantation and who may
benefit from different interventional approaches.
PMID- 11013973
TI - [Is Na+Ca(2+) exchanger expression altered in the endomyocardium of patients with
chronic heart valve diseases parallel to myocardial dysfunction?].
AB - BACKGROUND: Na(+)-Ca2+ exchanger (EXCH) is an important regulator of
intracellular calcium homeostasis. To maintain a normal intracellular Ca2+
concentration, EXCH expression may be upregulated before the onset of end-stage
heart failure. We tested for a correlation between the EXCH transcription level
and the degree of myocardial dysfunction as well as the suitability of EXCH
transcription as a molecular marker for early detection of a transition from
adequate to inadequate myocardial adaptation to chronic pressure and/or volume
overload in valvular heart disease (VHD). METHODS: The level of EXCH
transcription was analyzed in myocardial biopsies from eleven patients with
aortic stenosis (AS), five with aortic regurgitation (AR) and six with primary
mitral regurgitation (MR) of different hemodynamic severity and myocardial
impairment using the quantitative rt-PCR technique. In addition, endomyocardial
tissue from thirteen explanted hearts with end-stage heart failure and biopsies
from seven individuals without heart disease were investigated. RESULTS: The mean
level of EXCH transcription in patients with AS was: 1.8 +/- 1.4 amol/ng total
RNA, with AR: 1.9 +/- 0.8 amol/ng and with MR: 2.2 +/- +2.1 amol/ng. This was not
from different controls (2.6 +/- 1.2 amol/ng total RNA). However, in myocardium
from end-stage heart failure, EXCH transcription was increased fourfold amounting
to 8.9 +/- 1.9 amol/ng total RNA. No difference in the EXCH transcription was
found in VHD with respect to the degree of myocardial dysfunction: cardiac index
(CI) > 3.5 l/min/m2 (EXCH 1.4 +/- 1.1 amol/ng total RNA); CI 3.5-2.4 (EXCH 2.5 +/
1.8); CI < 2.4 (EXCH 1.8 +/- 1.0); EF-angio > 50% (EXCH 1.9 +/- 1.8); EF-angio <
or = 50% (EXCH 1.9 +/- 0.9); EF-RNV > 50% (EXCH 2.4 +/- 1.8), EF-RNV < or = 50%
(EXCH 1.7 +/- 1.0). CONCLUSION: Myocardial EXCH transcription does not change
parallel to the degree of myocardial dysfunction in VHD. Consequently, myocardial
EXCH transcription does not appear to be suitable as a parameter indicating the
transition from adequate to inadequate myocardial adaptation to chronic volume
and/or pressure overload.
PMID- 11013974
TI - [Impediment of cellular immune response under treatment with ticlopidine in a
patient with Staphylococcus aureus endocarditis].
AB - A 52-year-old male with coronary artery disease was admitted with acute aortic
valve endocarditis and a temperature up to 39.5 degrees C caused by
Staphylococcus aureus. The patient was treated with ticlopidine (Tiklyd) after
percutaneous transluminal coronary angioplasties to reduce restenosis by
inhibiting thrombocyte aggregation. Upon admission c-reactive protein (CRP) was
389 mg/l. Interleukin-6 (IL-6) and Interleukin-2-receptor (IL-2-rec) were
distinctly increased. Monoclonal antimyocardial antibodies were found. Leukocyte
count never exceeded 9.8 G/l; however, transesophageal echocardiography validated
a soft vegetation of the aortic valve. Antibiotic therapy was initiated with
imipenem, gentamicin and vancomycin; clarithromycin was added after five days.
Temperature normalized after 24 days. The c-reactive protein decreased from 389
mg/l to 6 mg/l, and the elevated cytokine levels decreased accordingly.
Agranulocytosis or pancytopenia by ticlopidine through a toxic mechanism have
been described, which are normally reversible within three weeks; there has not
yet been a description of a missing leukocyte response in endocarditis as in this
case report. This is a special situation with lack of or impeded immunological
response, which limits the use of ticlopidine, especially since a therapeutic
alternative with clopidogrel is available.
PMID- 11013975
TI - [Fibrinolytic therapy in thrombosis of a mitral valve prosthesis].
AB - A 48-year-old woman presented with progressive dyspnea due to thrombosis of a
mitral valve prosthesis. The patient had undergone mitral valve replacement (St.
Jude Medical) six years prior to admission because of mitral stenosis (Class
III); three years later the prosthesis had to be replaced (St. Jude Medical)
because of valve thrombosis. At admission, transesophageal echocardiography
showed a thrombus on the atrial side of the fixed valve leaflet and a thrombus
(2.4 x 1.6 cm) floating from the left atrial roof. Because of the previous
thoracotomies, thrombolysis was initiated despite the mobile thrombus with the
attendant risk of embolization. Urokinase was infused in a dose to maintain the
fibrinogen level around 100 mg/dl. After 24 h, the mean pressure gradient across
the prosthetic mitral valve (measured by doppler echocardiography) had decreased
from 23 to 11 mmHg. After 13 days of this modified thrombolytic regimen, the
clinical symptoms of the patient had resolved and echocardiography showed a
normal function of the prosthetic mitral valve without evidence of residual
thrombosis. This patient demonstrates that prolonged cautious thrombolysis can be
effective for the treatment of prosthetic valve thrombosis in hemodynamically
moderately compromised patients.
PMID- 11013976
TI - [Ventricular septal aneurysm in a patient with Marfan syndrome].
AB - This is the first description of a patient with Marfan syndrome and an aneurysm
of the ventricular septum. Apart from a borderline dilatation of the ascending
aorta, there were no cardiovascular manifestations of Marfan syndrome. A
transesophageal echocardiographic examination showed a large aneurysm of the
ventricular septum. To prevent the imminent rupture and the acute occurrence of a
significant left-to-right-shunt on the ventricular level, as well as increasing
irritation of tricuspid valve, an elective operation was performed. Besides the
routine cardiological diagnostics, the search for intracardial defects is also
necessary in patients with Marfan syndrome.
PMID- 11013977
TI - [Recommendations of the International Cardiology Forum (ICF) 1998 on revision of
the current guidelines for the diagnosis and treatment of unstable angina
pectoris and nontransmural myocardial infarct].
AB - Rapid progress in the understanding and treatment of unstable angina and acute
coronary syndrome are prompting occasional revisions to current treatment
guidelines. The recommendations contained in this paper are based on the
consensus reached during discussions at the 'International Cardiology Forum' in
September 1998. Consensus was reached on significant major points, although some
aspects remain controversial. A substantial body of data accumulated in a host of
studies justify changes to current treatment habits.
PMID- 11013978
TI - [Use of Abciximab in threatening vascular occlusion after PTCA].
AB - The administration of GP IIb/IIIa antagonists has been shown to be effective in
reducing myocardial infarction and cardial death when given before PTCA. This
prospective study was performed to determine the efficacy of abciximab in a bail
out situation to manage threatened or acute vessel closure. METHODS: Acute or
threatened vessel closure was observed in 104 (5.5%) out of 1903 consecutive
patients treated with PTCA in our institution. Of the 104 patients 46 (44%) were
treated for unstable angina (CCS IV). Abciximab was administered in bail-out
situations in a dosage of 0.25 mg/kg given as a bolus, which was followed by an
intravenous infusion of 10 micrograms/min over 12 hours. Repeat PTCA was
performed shortly after the administration of the abciximab bolus. After the
procedure, the sheath was left in place and control angiography was carried out
24 h later. RESULTS: In 100 of the 104 patients TIMI flow III could be restored
by abciximab therapy and RePTCA. In 4 patients an additional stent implantation
was necessary due to persistent flow limitation. One day post PTCA, early follow
up angiography demonstrated patency of all vessels except two. In-hospital events
occurred in 4 patients. Three of these patients underwent emergency CABG due to
subacute vessel closure a few hours after PTCA and died during or directly after
surgery. Follow-up after one year included clinical status and control
angiography of the target vessel. During long-term follow-up, MACE occurred in 15
patients (2 MI, 8 CABG and 5 RePTCA). CONCLUSION: The results of this prospective
trial demonstrate the efficacy of abciximab therapy in bail-out situations
occurring during or early after PTCA. The use of abciximab in bail-out situations
appears clinically beneficial. Further studies have to compare the efficacy of
this approach with prophylactic abciximab treatment.
PMID- 11013979
TI - [Ross operation in aortic valve diseases].
AB - Currently used standard mechanical and bioprosthetic heart valves all have
limitations that produce less than optimal results. The pulmonary autograft
offers a promising alternative with theoretical advantages that have to be proven
for final judgement of this innovative surgical technique. METHODS AND RESULTS: A
survey including the international registry with 2523 patients enrolled since
1987 is provided along with the author's 10 years experience of 157 patients. The
age of the patients ranges between one and 79 years. The indication is expanding
integrating concomitant procedures like repair or replacement of aneurysms of the
aortic root and ascending aorta, mitral valve reconstruction, coronary bypass
grafting, etc. The operative mortality ranges between 0.6 and 2.5%. No
anticoagulation is necessary. The function of the autograft is excellent. Late
incidence of significant aortic insufficiency (> 2+) remains less than 5%. Even
at exercise there is no pressure gradient across the autograft. Autograft failure
with autograft revision or replacement stands at 1-4%. Homograft function is also
found to be excellent. Right ventricular outflow tract revision rate ranges
between 1-1.3%. In a few patients (7%), maximal pressure gradients between 20 and
35 mmHg developed across the homograft without major impairment of right
ventricular function. CONCLUSIONS: The multicenter data confirm the superior
performance of the autograft not matched by any other biological or mechanical
valve replacement. Scientific efforts are required to further improve long-term
function especially of the neopulmonary valve.
PMID- 11013980
TI - ["Vacation, again...?"].
PMID- 11013981
TI - [Responsibility of the rheumatologist in skeletal radiology. A contribution to
the "Bone and Joint Decade"].
PMID- 11013982
TI - [Patient education in rheumatology--quality control].
PMID- 11013983
TI - [Spinal stiffness. Differential imaging diagnosis with reference to acquired
hyperostosis syndrome and spinal loading disease].
AB - There are numerous diseases which can irreversibly stiffen the whole spine or
parts of the axial skeleton. Due to didactic reasons one can distinguish 3 groups
of such disorders: Paradigmatic diseases of the spine with an inherent proneness
to stiffness. Rare diseases which involve a certain danger of stiffening the
spine. Rigidity of the spine due to scientifically unrecognised morphologic
phenomena.
PMID- 11013984
TI - [Possibilities and limits of conservative therapy of spondylitis and
spondylodiscitis].
AB - BACKGROUND AND AIM OF THE STUDY: For many years the treatment of spondylitis and
spondylodiscitis has been discussed controversially. The aim of this study is to
report on objective and subjective mid-term results of therapy of spondylitis and
to present a differentiated concept of treatment. METHODS: Between 1988 and 1996,
58 patients were treated with spondylitis or spondylodiscitis. Nine of these
patients had to be operated. A biopsy was taken in all of the cases. According to
the antibiogram obtained by the biopsy, antibiotics were applied intravenously.
The patients were immobilized by a plaster bed for at least 6 weeks and were then
treated by a spinal orthosis for another 3 months. Patients were re-examined
clinically and radiographically and by a questionnaire (including Roland-Morris
score), after 8 years on average. RESULTS: Patients were diagnosed correctly 4
months after the begin of the disease. Spondylitis was predominantly localized in
the lumbar spine. A positive bacteriological culture was derived from one third
of the biopsies; none of them was a specific culture. C-reactive protein was
revealed as appropriate for diagnosis and follow-up of spondylitis. In 84% of the
patients a total or partial bony fusion was demonstrated radiographically.
Questionnaire assessment revealed a significant decrease of the Roland-Morris
score (17.8-7.4) and a significant relief of pain (8.9-2.5). CONCLUSIONS: We
recommend surgical treatment on patients with major vertebral body destruction,
epidural abscess and progressive neurological impairment. These indications for
operation can be prevented by a rapid diagnosis, so that spondylitis can be
successfully treated by consequent immobilization in a plaster bed and
appropriate antibiotics.
PMID- 11013986
TI - Network Symposium Rheumatology and Clinical Immunology. March 23-25, 2000,
Berlin, Germany. Proceedings and abstracts.
PMID- 11013985
TI - [Mixed tophi. Calcium pyrophosphate dihydrate crystals in gout tophi].
AB - Calcification of tophi is a well-known secondary phenomenon in gout. Because
there are no data available on the nature of the calcium component, light and
scanning electron microscopic as well as X-ray microanalysis studies were
performed on calcified tophi. In unstained histological slides, urate crystals
were detected as negative birefringent needles; after incubation of the slides in
distilled water, the urate crystals had disappeared, only positive birefringent
calcium pyrophosphate dihydrate (CPPD) crystals of different size remained. An
identical result was obtained by scanning electron microscopy. By X-ray
microanalysis, peaks for calcium and phosphorus were measured, indicating the
presence of CPPD. The occurrence of CPPD crystals in urate tophi as well as in
foreign body granulomata indicates that the occurrence of CPPD is not restricted
to articular tissues. The biochemical mechanism leading to the appearance of
these crystals remains unknown, but it may be assumed that an increase of
connective tissue destruction may be responsible for this calcification process.
PMID- 11013987
TI - [Quality standards of the German Society of Rheumatology for Rheumatologic
Patient Education--preliminary report, discharged by the governing body and with
consultation of the German Society of Rheumatology in September 1999].
PMID- 11013988
TI - [Recommendations of the German Society of Rheumatology for therapy with tumor
necrosis factor inhibitors. Pharmacotherapy Committee of the German Society of
Rheumatology].
PMID- 11013989
TI - [Anesthesiological care in removal of bulky formations from functionally
important hemispheric zones: craniotomy in conscious state].
AB - A method of anesthesia allowing patient's awakening to the level of verbal
contact after trephination and opening of the dura mater was used in 37 patients
with bulky formations (33 patients with tumors and 4 with arteriovenous
malformations) in the speech zones of speech-dominant hemisphere. Speech mapping
of the brain, carried out in alert patients, helped eliminate permanent speech
deficiency during the postoperative period in all patients. The protocol of
anesthesia was as follows: locoregional anesthesia of soft tissues of the head
with a mixture of 2% xylocaine and 0.5% marcaine with epinephrine intravenous
diprivan at stages requiring no patient's alertness, clopheline, fractionated
midazolam (after identification of speech zones). The study showed that this
protocol helps solve the problem and adequately protects the organism from
surgical stress, provides good conditions for manipulations on the brain,
involves no unpleasant sensations for the patient, and in 70% patients helps
attain complete amnesia of the perioperative period. The most severe complication
is an epileptic attack. Respiratory monitoring (pulse oximetry and capnography in
the lateral duct) is obligatory for preventing respiratory disorders in patients
on spontaneous respiration who were not intubated.
PMID- 11013990
TI - [Cerebral oximetry in neurosurgical patients with cerebrovascular diseases. I.
Analysis of causes of intraoperative changes in rSO2 values and its prognostic
significance].
AB - A total of 144 neurosurgical interventions were performed in 138 patients with
cerebrovascular diseases (arterial aneurysms in the acute and cold periods after
a subarachnoidal hemorrhage, arteriovenous malformations, and carotid-cavernous
anastomoses). Intraoperative monitoring of regional saturation of hemoglobin with
oxygen in the blood flowing in brain vessels was carried out by a cerebral
oximeter INVOS 3100 for early intraoperative diagnosis of cerebral ischemia. This
paper analyzes factors affecting changes in rSO2 parameter during surgery and
discusses the prognostic significance of the detected shifts. Various factors
affected the time course of rSO2: decrease in AP within the framework of
controlled arterial hypotone and other causes, insertion of autosupported
retractor spatulae, temporary clipping and embolism of cerebral arteries,
vasospasm, aneurysm rupture, dissection of arteriovenous malformation, etc. Any
intraoperative shift of rSO2 surpassing 5%, no matter of what direction (decrease
or increase), deserves special attention of anesthesiologist, as it indicates
development of cerebral ischemia with a high degree of probability.
PMID- 11013991
TI - [Cerebral oximetry in neurosurgical patients with cerebrovascular diseases. II.
Comparison of electrophysiological methods of examination and cerebral oximetry].
AB - Simultaneous monitoring by cerebral oximetry and electrophysiological methods
(electroencephalography and electrocorticography) was performed in 21 patients
with arterial cerebral aneurysms during direct intracranial interventions,
endovascular interventions, and Matas' test. Electrophysiological methods are
sufficiently accurate indicators of cerebral ischemia even at a functionally
reversible level. The results of simultaneous monitoring were similar in 80%
cases, indicating cerebral ischemia even at functionally reversible level, which
was detected by both electrophysiological methods and cerebral oximetry.
Variously directed shifts were detected in 4 cases; the causes are discussed.
Cerebral oximetry detects cerebral ischemia with a sensitivity similar to that of
electrophysiological methods. The method does not depend on temperature or
anesthetics. Limitations of the method are due to its local application.
PMID- 11013992
TI - [Pharmacological protection of the brain during surgery in patients with giant
cerebral aneurysms].
AB - The authors discuss the results of pharmacological protection of the brain,
consisting in intraarterial or intravenous infusion of drugs (sodium thiopental,
nimodipine, ketamine) during intracranial interventions in 13 patients with giant
arterial aneurysms of the anterior portions of Willis' circle. In some patients
drug protection of the brain prevented the development of ischemic focus in the
basin of temporarily occluded vessel. Intraarterial infusion of protector drugs
is preferable because it allows decreasing the doses and severity of untoward
hemodynamic effects.
PMID- 11013993
TI - [Epidural anesthesia in surgical interventions on the spine and spinal cord. I.
Comparative analysis of the effectiveness of anesthesiological protection under
conditions of epidural anesthesia and neuroleptanalgesia in surgery of the spine
and and spinal cord].
AB - The study was carried out in 22 patients operated on for vertebral disk hernias
and spinal tumors at lumbosacral level. The patients were divided in 2 groups
depending on the type of anesthesia (epidural or neuroleptanalgesia-EA and NLA).
In the test group all patients were operated under EA with local anesthetics
combined with intravenous sedative drugs (diprivan + relanium) under conditions
of spontaneous respiration and O2 inhalation through a mask. In the control group
combined total intravenous anesthesia by myorelaxants and tracheal intubation
were carried out (relanium + diprivan: induction dose 1.95 +/- 0.5 mg/kg,
maintenance dose 5.3 +/- 0.4 mg/kg/h, and phentanyl). The purpose of the study
was to compare the efficiency of anesthesiological protection under EA and
traditional NLA in interventions on the spine, when surgical injury is inflicted
in the immediate vicinity to the central structures responsible for pain
impulsation. Only EA ensured adequate protection of the patients from surgical
stress, as was seen from hemodynamic (arterial pressure and heart rate) and
endocrine metabolic parameters (glucose, epinephrine, norepinephrine,
hydrocortisone, and prolactin levels). Hence, EA fully demonstrated its
protective properties during operations on the spine, and therefore can be
regarded as a method of choice in this patient population.
PMID- 11013994
TI - [Epidural anesthesia in surgical interventions on the spine and spinal cord. II.
Effects of epidural anesthesia on somatosensory evoked potentials].
AB - Effects of epidural anesthesia (EA) on early components of somatosensory evoked
potentials (SSEP) were studied and the objectiveness and efficiency of SSEP
monitoring during interventions on the spine under EA were evaluated. Evoked
potentials were studied in 21 patients operated on for vertebral disk hernias and
extra-intradural tumors of the spine (lower thoracic and lumbar levels) under
bupivacaine EA. Cortical SSEP were recorded and analyzed on a Viking IV
neuroaverager (Nicolet, USA) stimulating n. tibialis posterior for obtaining a
greater amplitude of evoked potentials. The following SSEP characteristics were
measured: latency of PI (P37), NI (N45), and PII (P60) peaks, amplitude of PINI
peak, and inter-peak latency of PI-NI and PI-PII. The major changes in cortical
SSEP caused by EA (local anesthetic 0.5% bupivacaine) involve only PI and NI
components which reflect the entry of information on an external stimulus into
the cortex and objective physical parameters of this stimulus; this helps predict
the onset of full-value epidural block and its duration. General anesthetic
(propofol) affect mainly a later component of response, PII peak, which is
responsible for processing of primary information about an external stimulus and
reflects the activation of associative areas of the brain. Hence, SSEP regulation
can be used together with traditional methods (pin prick test and Bromage scale)
for evaluating epidural block in patients with spinal diseases.
PMID- 11013995
TI - [Early awakening or prolonged sedation after neuroanesthesia: which is better for
the patient?].
PMID- 11013996
TI - [Anesthesia in magnetic resonance tomography].
AB - Sixty patients were anesthesized for MRI. Intravenous and/or intramuscular
anesthesia with ketamine, diazepam, pipolphen (promethazine) was supplemented by
aminazine (chlorpromazine) or tisercin for adult patients. Spontaneous
respiration was maintained, which helped avoid problems with endotracheal
intubation and assisted ventilation. The method is safe, economic, and its side
effects are negligible. Main features of MRI and specific anesthesiological
problems associated with this method are discussed.
PMID- 11013998
TI - [Effects of various protocols of respiratory support on hemodynamics in
neurosurgical patients].
AB - Central hemodynamics is analyzed in neurosurgical patients during application of
various methods of assisted ventilation. Invasive monitoring of central
hemodynamics was performed during respiratory support of neurosurgical patients
for the first time in Russia. Gradual decrease of PSV helps evaluate the
readiness of patients to decrease of respiratory support. Metabolic respiratory
oxygen value at least 37%, cardiac index at least 4.5 +/- 0.5 liter/min x cm2,
and working load of the left and right heart at least 6.7 +/- 0.75 and 0.71 +/-
0.183 kg/m(min x m2), respectively, are hemodynamic criteria for transferring to
spontaneous respiration.
PMID- 11013997
TI - [Basic intensive care of ischemic cerebral stroke. Method of therapeutic
hemodilution].
AB - Ischemic cerebral stroke (ICS) ranks among the most frequent causes of
disability. The incidence of untoward consequences of ICS can be decreased by
early adequate use of intensive care methods restoring tissue oxygenation in the
focus. The most important methods of intensive care of ICS are measures notably
improving microcirculation and essentially decreasing subsequent incidence of
disabling complications. The basic component of intensive care ensuring favorable
results is therapeutic hemodilution making use of modern plasma substitutes-
second-generation hydroxyethyl starch Infukoll HES 6 and 10% solutions. Currently
used methods including use of dextran-based solutions cannot normalize
microcirculation in ICS patients, particularly if used in long course. Prolonged
infusions of dextran-based solutions inevitably increases plasma viscosity and
impairs the hemostasis system. An essential increase of plasma viscosity involves
the need in a complex of appropriate drug therapy aimed at compensation for
untoward aftereffects of high dextran doses. Therapeutic doses of dextran-based
solutions do not notably improve blood rheology. By contrast, therapeutic
hemodilution with Infukoll HES notably improves the results of intensive care of
ICS.
PMID- 11013999
TI - [Nosocomial pneumonia in patients with severe craniocerebral trauma in intensive
care units].
AB - Eighty-three patients with severe craniocerebral injuries (CCI) were treated at
Institute of Neurosurgery in 1999. Pulmonary infectious complications occurred in
16 of 25 patients with severe CCI. Early nosocomial pneumonia (NP) was diagnosed
in 18% and the so-called late NP (associated with artificial ventilation of the
lungs) in 35%. Coma longer than 4 days increased the incidence of NP to 62%. The
main pathogens of NP are gram-negative aerobic bacteria (61%), the predominant
agent being Pseudomonas aeruginosa (18.9%). 76% isolated microorganisms were
multiresistant. The most significant risk factors as regards NP in patients with
severe CCI were coma combined with bulbar and pseudobulbar disorders.
PMID- 11014000
TI - [Principles of intensive care during the acute period of severe craniocerebral
trauma in children].
AB - Prospective analysis of the course of severe craniocerebral injury (CCI) in 37
children showed that the results of treatment depended on methods of intensive
care. In children the outcome of CCI depends primarily on adequacy of maintaining
effective cerebral bloodflow during the acute period of CCI irrespective of the
terms and etiological factors of coma. Adequate cerebral perfusion pressure is
attained with osmodiuretics, saluretics, and hemodynamic therapy.
Hyperventilation is justified in cases with coma developing within 2 h after the
injury; it should not lead to long (more than 1 h) decrease of PaCO2 below 28 mm
Hg. The authors emphasize that every delayed decrease of consciousness after the
injury should be thoroughly analyzed in order to rule out intracranial
complications (epi/subdural and intracerebrai hematomas) in no more than 6 h,
which is the maximal time allowed for decision making. Use of unapproved medical
methods and drugs in children during acute period of severe CCI is ineffective
and even hazardous, because it distracts the physician's attention to negligible
details of treatment; in addition many of such drugs have side effects.
PMID- 11014001
TI - [Respiratory failure in disseminated sclerosis].
AB - The development and patterns of respiratory failure (RF) are analyzed in 9
patients with disseminated sclerosis (DS). Forced ventilation of the lungs was
carried out with consideration for main location of the process. Relationship
between patterns of respiratory disorders and neuroanatomy of respiratory
regulation is discussed. Involvement of the corticospinal routes is paralleled by
dissociation during functional pulmonary tests: spontaneous volumes are less than
controlled inspirations. The most severe symptom complexes were observed in RF of
predominantly bulbar localization: respiratory anarchy, blocking of airways
caused by impaired swallowing, impaired mechanism of coughing reflex, loss of
spontaneous respiration, sometimes apnea during sleeping. Involvement of the
respiratory nuclei of medullary respiratory center and airways and of the
corticonuclear routes of caudal cranial nerves causes the development of a triad
of symptoms: glossopharyngolaryngeal paralysis, dysfunction of respiratory nuclei
of medulla oblongata, and decreased sensitivity of respiratory center to CO2.
Aspiration complications caused by dysphagia are characteristic of bulbar DS.
Respiratory function in 5 patients without clinical picture of RF are specially
discussed. The authors emphasize unfavorable prognostic significance of signs of
extracorporeal obstruction indicating the probability of RF long before its
manifestation. Special attention is paid to early diagnosis of symptoms of coming
RF when evaluating the status of patients with DS during treatment. Timely use of
respiratory resuscitation methods reduces the mortality and ensures a good chance
for remissions with recovery of respiratory function, which are characteristic of
RF.
PMID- 11014002
TI - [Videofluoroscopy study of swallowing in neurogenic dysphagia].
AB - Videofluoroscopy (VFS) was for the first time used for examining swallowing in 49
patients with nervous diseases. Disturbances in each phase of swallowing act are
analyzed with evaluation of the time parameters and defects, causes of aspiration
in neurogenic dysphagia are discussed, and cricopharyngeal insufficiency is
described. Neurogenic dysphagia is characterized by a combination of disorders
which determine the degree of dysphagia. The most severe swallowing disorders
were observed in patients with multiple foci in the brain stem and in
diphtheritic polyneuropathies. The authors conclude that VFS is the optimal
method for the diagnosis of neurogenic dysphagia.
PMID- 11014003
TI - [Prevention of postoperative venous thromboembolic complications].
AB - Venous thromboembolic complications (VTEC) occurring during the postoperative
period notably increase the mortality. Prevention of this complications requires
detection of risk factors in order to evaluate the risk for every patient. Based
on the risk factors described in this paper, all patients can be divided into
categories at a high, moderate, and low risk of complications. Preventive
measures corresponding to the risk are to be taken. These measures are to include
measures improving venous flow and anticoagulant therapy (low-molecular heparins
should be preferred). Though these measures do not 100% prevent thromboembolic
complications, they notably decrease the risk of VTEC.
PMID- 11014004
TI - [New long-acting local anesthetic: ropivacaine hydrochloride (naropin)].
PMID- 11014005
TI - [Case of uncommon motor reaction to administration of diprivan].
AB - A young patient without history of epilepsy developed a pronounced motor reaction
simulating an epileptic attack in response to diprivan. Possible causes of motor
excitation in response to diprivan and probability of their prediction are
discussed.
PMID- 11014006
TI - ["Artificial liver"].
AB - Acute liver failure is a life-threatening condition since conventional medical
treatments have little effect on survival. Artificial liver support systems based
on blood detoxification alone have proven to be ineffective. A liver support
system should carry out essential functions such as the phase I reaction in which
lipid-soluble toxic substance are rendered water-soluble by the enzyme system of
the cytochrome P450 and NADPH-cytochrome reductase, and are therefore conjugated
by the phase II reaction, before excretion. Liver support systems should be
capable of sustaining patients until an organ is available for liver
transplantation (bridging treatment), or improving the survival in patients for
whom liver transplantation is not a therapeutic option. Recent advances in cell
biology and tissue culture techniques have led the way for potential clinical use
of isolated hepatocytes so that they are now an important element of
bioartificial liver (BAL) support devices. Some of these BAL are currently under
clinical investigation in the USA and Europe, and the results of the prospective
controlled trials will be soon available.
PMID- 11014007
TI - [Fulminant liver failure: etiopathogenesis and therapy].
AB - Fulminant hepatic failure (FHF) is a clinical syndrome characterized by the
development of encephalopathy within eight weeks from the onset of the first
symptoms, in the absence of previous hepatic disease. It is an uncommon but not
rare disease, often fatal but potentially reversible. This article looks at the
diverse aetiologies, clinical features, and current medical management, including
orthotopic liver transplantation, and auxiliary orthotopic or eterotopic liver
transplantation, that are the most recently adopted surgical procedures. Clinical
experience with bio-artificial liver support systems of two of the most active
research Groups in this field, concludes the paper.
PMID- 11014008
TI - [Acute and fulminant liver failure: experimental models].
AB - Fulminant hepatic failure (FHF) is a complex clinical syndrome, with an
invariably high mortality rate, that follows many possible and different
infectious, pharmacologic and surgical liver injuries. The appearance of the
syndrome is similar whatever the etiology, but the mechanisms which lead to the
development of FHF are greatly varied. In order to understand the possible
pathways which drive to FHF, experimental animal models have been used for a long
time. Six requirements should be fulfilled by any FHF animal model: 1)
reversibility; 2) reproducibility; 3) death from liver failure; 4) the presence
of a therapeutic window; 5) the need of large laboratory animal; 6) minimal
hazard to personnel involved in the study. In the present paper a number of
models are reported and described, and advantages and disadvantages are
discussed. It is concluded that with respect to the aforementioned criteria, no
available experimental model is yet as satisfactory as expected.
PMID- 11014009
TI - [Acute liver failure in chronic hepatic disease. Clinico-therapeutic evaluation].
AB - Chronic liver diseases are potentially evolving clinical situations which,
independently by the etiology, could proceed towards progressive liver structural
and functional impairments. The only efficient treatment is orthotopic liver
transplantation. Chronic liver diseases, and up to 40% of liver cirrhosis, are
initially asymptomatic, but cirrhosis is the most frequent cause of death among
non-neoplastic digestive diseases. Important elements complicating a
decompensated liver cirrhosis are ascites, hepatic encephalopathy, digestive
bleeding and jaundice. Acute liver failure (ALF) is the expression of a clinical
state, that is common to many conditions sharing severe liver structural and
functional impairments. In patients affected by decompensated liver cirrhosis,
ALF could be triggered by several factors, while the death is caused by bleeding
episodes, hepato-renal syndrome, spontaneous bacterial peritonitis or
hepatocarcinoma. In patients affected by chronic liver diseases, the diagnosis of
ALF is based on progressively increasing jaundice, encephalopathy and
coagulopathy. Recent clinical trials have evaluated the efficacy of extrahepatic
liver support systems, either artificial or bio-artificial, in treating episodes
of ALF in chronic liver patients. The preliminary results indicate a potential
use of such systems in blood detoxification, but they also showed limits in
increasing patient survival.
PMID- 11014010
TI - [Hybrid (bioartificial) systems for liver support. History and current
developments].
AB - Attempts to develop liver support systems for the treatment of acute liver
failure patients have ranged in the past, from the use of hemodialysis, or plasma
exchange, or activated charcoal particles and synthetic resins, as well as the
use of bioreactors loaded with liver tissue. However, no system demonstrated a
significant improvement of patient survival, nor has achieved a wide clinical
use. Liver transplantation remains the only treatment for severe hepatic failure
that can improve patient survival. On the other hands, the chronic scarcity of
organs for transplantation, leads to an urgent necessity of liver support
systems. In this paper, we reviewed the historical experience and current status
of artificial liver support systems, with particular emphasis on the so-called
hybrid or bioartificial liver, in which to the traditional artificial components,
such as selective membranes, charcoal particles and resins, isolated hepatocytes
are used.
PMID- 11014011
TI - [Artificial liver support systems: state of the art].
AB - Previous attempts in improving the outcome of acute liver failure patients were
based on extracorporeal artificial systems such as hemodialysis, hemoperfusion,
plasmaperfusion, hemoadsorbtion and plasma exchange. Despite more than 30 years
of research and development in this field, an artificial liver has still not
become a reality, since purely artificial support systems have shown only minor
improvement in patient's survival, and orthotopic liver transplantation is the
only effective cure. This review takes a critical look at past and present
concepts for an artificial liver support system, evaluating the advantages and
disadvantages of the aforementioned techniques. Progress in methods and
techniques for maintaining long-term hepatocyte culture in vitro indicate the
potential use of isolated liver cells in bioartificial liver support systems.
Recent studies suggest the use of traditional artificial liver support systems,
such as hemoadsorbtion or plasma-absorbtion on activated charcoal particles or
synthetic ion-exchange or neutral resins to improve and prolong the efficiency of
the so-called hybrid or bioartificial liver, in which isolated hepatocytes are
used.
PMID- 11014012
TI - [Isolated hepatocytes and their potential therapeutic use].
AB - Isolated hepatocytes in culture represent an idoneous system for the study of
liver physiology and metabolism. Furthermore, they are also widely utilized in
pharmacological and toxicological study, in evaluating xenobiotic substance
effects on the liver. In this paper, we reviewed the enzymatic methods for liver
cell isolation in some mammalian species, as well as the techniques for
qualitative and quantitative evaluation of cell number, vitality, purity,
morphology and function. Recently, there has been a renewed interest in
hepatocyte transplantation and hepatocyte-based liver support systems. From a
clinical point of view, isolated hepatocytes could be useful in temporarily
substituting an acutely damaged liver, a liver affected by a chronic pathology,
or to correct an inherited liver disease carrying a severe metabolic derangement.
Early experimental results of allogeneic hepatocyte transplantation, as well as
the first clinical trials of bioartificial liver support systems employing
xenogeneic hepatocytes are promising and contribute to maintain that interest in
liver cell isolation and purification methods.
PMID- 11014013
TI - [In vitro experimentation of a new model of radial flow bioreactor containing
isolated hepatocytes].
AB - Hepatocyte based artificial liver support systems are under investigation to
support acute liver failure patients. The main purpose of such systems is to
serve as a bridge to liver transplantation, or to promote spontaneous liver
recovery. Limitation in mass-transfer capacity makes hollow-fiber bioreactors
unsuited for long-term functioning of hybrid devices. We developed a novel radial
flow bioreactor in which the fluid perfuses the module from the center to the
periphery, after having diffused through a space occupied by a three-dimensional
structure filled with the hepatocytes. Five grams of freshly isolated porcine
hepatocytes were seeded into uncoated, woven-non woven, hydrophilic polyester
fabric, overlaid by two polyethersulfone membranes. Liver cells were perfused
with 37 degrees C-warm, oxygenated, serum-free tissue culture medium, in which
NH4Cl and Lidocaine were added at the final concentration of 1 mM and 60
micrograms/ml, respectively. Ammonium chloride removal, urea synthesis,
monoethylglycinexylide (MEGX), pO2, pCO2, and pH were measured throughout the 14
day duration of the study. In a separate set of experiments, a scaled-up version
of the radial flow bioreactor containing 150 grams of cells was perfused for 7 h
with recirculating human plasma and MEGX production was monitored. During the 2
weeks of the study, an increasing production of urea was paralleled by constant
ammonium removal. MEGX concentration after Lidocaine addition increased
throughout the 14 days of perfusion with tissue culture medium, as well as after
7 hour perfusion with human plasma. Under transmission and scanning electron
microscopy cells appeared attached to the polyester and one to each other,
displaying ultrastructural features typical of functioning hepatocytes. Our study
showed that liver cells were metabolically active when perfused into the radial
flow bioreactor. This configuration allowed close contact between media, or
plasma, and cells at a physiological flow rate, by equalizing the concentration
of the perfusing components, including O2, throughout the module. Our results
suggest a potential use of this system for temporary extracorporeal liver support
in acute hepatic failure patients.
PMID- 11014014
TI - [Therapeutic approach in Riedel thyroiditis].
AB - Riedel's invasive fibrous thyroiditis is a rare disorder of unknown origin with
progressive extension and invasion of adjacent structures. Clinically it is
impossible to distinguish between Riedel's/thyroiditis and other diseases as
undifferentiated carcinoma, Hashimoto's disease etc... The patients often have
dyspnea, dysphagia, paralysis of the vocal cord; fine needle puncture-aspiration
and biopsy themselves may be insufficient, Surgical treatment depends on the
stage of the disease, when both lobes are involved generous wedge resection of
the isthmus may be the treatment of choice to relieve tracheal compression; in
earlier stages radical operation are considered. Corticosteroid treatment in
Riedel's thyroiditis, as multifocal disease has been successfully used. Other
drugs with antifibrosing actions have also utilised in small groups of patients
with encouraging results.
PMID- 11014015
TI - [Our experience with duodenal tumors].
AB - The authors report 3 cases of benign duodenal tumors and one case of duodenal
cancer. In two cases the benign tumors were adenomatous polyps, in one case with
signs of dysplasia. One case of benign tumor was a lipoma. All the three benign
tumors were removed through a duodenotomy, in one case associated with a
sphincteroplasty. The case of duodenal cancer, arisen in a patient operated since
24 years with a gastric resection, was treated with a Whipple technique but for
the very old age and the bad health conditions, the patient died in 11th post
operative day for myocardium infarct.
PMID- 11014016
TI - [Indications for the surgical treatment of cavernous angioma of the liver in
adults. Report of a case].
AB - The authors report a case of giant cavernous hemangioma of the liver, almost
entirely extrahepatic, bulging from the inferior surface of the right lobe into
the abdomen, treated surgically on account of worsening symptoms referable to
continuing growth. A thorough search of the literature allows a critical review
of the surgical indication in this benign pathology, rarely complicated by
significant clinical events. Surgery is indicated, in lack of relevant
complications, only when significant symptoms, continuing or worsening, are
undoubtedly referable to the presence of the angioma.
PMID- 11014017
TI - [Retrospective analysis of the use of prophylactic drainage of the pelvis after
anterior resection of the rectum].
AB - Although the use of drains is common in clinical practice, its real role in the
prophylaxis and therapy of postoperative complications is still not clear. In the
literature we can find both supporters of drains, and many opponents who consider
their use unnecessary and sometimes even dangerous. In fact, during new
experimental and clinical studies, it was impossible to determine the usefulness
of prophylactic abdominal drain, at least in the case of colo-rectal anastomosis,
it has been demonstrated that use of drains limits the risks of an anastomotic
leakage but, in some cases, the same drains could be the cause of some of the
complications that should be avoided. Although there is a considerable
theoretical and practical evidences in favour of drainage, the dispute about "to
drain or not to drain" the peritoneal cavity after elective colo-rectal surgery
remains open. This retrospective study made on 150 patients operated on elective
surgery for rectal cancer demonstrates that prophylactic drain does not
significantly influence the general rate of leakage (3.15% for group A and 5.45%
for group B, p > 0.1); in two of the three fistulas in patients with drains, the
drains have permitted the diagnosis, but have not permitted the reduction of the
number of operations for fistulas.
PMID- 11014018
TI - [Unusual case of benign neoplasm of the breast mimicking a carcinoma: granular
cell tumor. Case report].
AB - Granular cell tumors are rare, usually benign neoplasms of soft tissues which
most commonly occur in the tongue, skin and subcutaneous tissue. Although the
histogenesis is still object of debate, recent immunohistochemical studies and
ultrastructural findings support the origin of this neoplasm from the peripheral
nervous tissue, most likely from Schwann's cells. Occurrence of this neoplasm in
the breast, although uncommon, warrants special attention, since its clinical,
mammographic and pathological appearances on frozen sections "may often closely
resemble" hose of breast malignancy. The authors analyze and commenton, with
special reference to clinical aspects and surgical treatment, a case of benign
granular cell tumor of the breast occurring in a 42 year-old woman. The
mammographic and clinical findings suggested a breast carcinoma. The correct
diagnosis was established by definitive microscopic examination of the paraffin
embedded specimens and the treatment was a simple local excision of the tumour
and a small rim of surrounding breast parenchyma. Although the granular cell
tumor of the breast is a rare entity, surgeons and pathologists should be aware
of its existence in order to avoid inappropriate radical surgery not justified by
the benign behavior of the neoplasm.
PMID- 11014019
TI - Spontaneous rupture of a giant hemangioma of the liver.
AB - Hemangiomas are frequent benign tumors of the liver. Symptoms (abdominal pain and
fullness) are mostly seen in giant lesions. Rupture is the most severe
complication, can occur spontaneously, with intraperitoneal bleeding, in 1-4% of
hemangiomas and has been described in about 30 cases in the international
literature with a high mortality (about 60%). This complication is the principal
indication for surgery. Although spiral CAT scan and MR are actually the most
efficacious imaging methods for study of liver hemangiomas, after Echography,
emergency techniques that allows a simultaneous therapeutic approach--as is
angiography--are preferable. Trans-arterial embolization (TAE) is in fact useful
to stop bleeding and then to perform a safer surgery. A successful embolization
can delay the surgical resection of the hemangioma for the time necessary to
recover from the hemodynamic distress. Aside from the success of angiographic
approach, surgery remains mandatory, effective in stopping the bleeding and in
preventing re-bleeding or other complications of TAE such as abscess, fever,
etc.. Intraoperative echography currently is the best method to identify vasculo-
biliary anatomy and to perform a correct resection. The absence of risk factors
for spontaneous rupture of liver hemangiomas, makes this event unpredictable. The
best treatment for non-ruptured hemangiomas is still controversial but surgery is
usually limited to symptomatic tumors larger than 10 cm.
PMID- 11014020
TI - [Adenocarcinoma arising on colo-rectal endometriosis: clinico-pathological
considerations].
AB - Colo-rectal endometriosis represents a rare pathological event. Exceptionally, a
malignant colo-rectal endometrioid carcinoma arising from endometriosis has been
reported. In the present case, we describe a 32 year-old woman with clinical and
radiological signs of large bowel sub-occlusive syndrome. Histologically, a
sigmoid endometrioid adenocarcinoma associated with submucosal foci of eutopic
endometrium was observed. Moreover, endometriotic tissue was observed at the
level of the colonic left flexura and appendix. Colo-rectal endometriosis must be
considered among risk factors for the development of large bowel adenocarcinoma
in young female patients.
PMID- 11014021
TI - [Umbilical endometriosis: report of a case and review of the literature].
AB - The authors present a clinical of umbilical endometriosis in a young woman. This
patient never underwent any operation or diagnostic abdominal procedures. The
case is very interesting because of problems concerning differential diagnosis
with other umbilical and periumbilical diseases and pathogenetic theories. In
this study the authors suggest a hypothesis to explain the localization of
ectopic endometrium in this site. We review the literature, with some comments on
therapeutic options; finally we compare the medical and the surgical approach and
we suggest an advisable therapy.
PMID- 11014022
TI - [Ileal occlusion caused by enterolith migrated from Meckel's diverticulum].
AB - The authors present a case report of an intestinal obstruction due to a
relatively big coprolite migrated from a large Meckel's diverticulum to the
distal Ileum. The patients apparently healthy and a vegetarian, complained on
admission of the absence of emission of faeces and gas since four days before
with noticeable abdominal distension. In the physical examination he presented
intestinal meteorism, a hard abdomen, painful on deep palpation in the median
quadrants, especially in the epigastric and mesogastric ones. The abdominal X-RAY
in the standing position confirms: an occlusive state with numerous liquid levels
in the Ileum. Because of a worsening of the symptomatology and the appearance of
generalized comprimission, two days later an exploratory laparotomy was
performed. The intervention showed the presence of a Meckel's diverticulum with
approximately 10 cm in length, with an ample neck, the distal Ileum for
approximately 15 cm in dilation returned rapidly to a normal calibre, after a
pastous endoluminal formation borne in the Meckel's diverticulum (Meckel
resection presented actually a large niche at the fundus level with a eroded
wall) and migrated in the distal Ileum where it could cause the obstruction. In
the present case it is probably useful to perform a preoperative CT scan in order
to get a precise etiology and perform an ascending Colonscopy, so avoiding a
surgical procedure. According to the authors a CT scan is indicated in all cases
of intestinal occlusion of unknown case, in order to have a more precise
definition of the physiopathology of the occlusion.
PMID- 11014023
TI - Ready, steady, go for HCV antigen testing?
PMID- 11014024
TI - Implications and importance of genotyping cryptosporidium.
PMID- 11014025
TI - Serological diagnosis of syphilis. PHLS Syphilis Serology Working Group.
AB - The availability of an increasing number of enzyme immunoassays (EIAs) for
detecting syphilis antibodies makes it appropriate to review approaches to
syphilis serology and to assess the role of syphilis EIAs in routine diagnostic
microbiology laboratories. This paper summarises the principles and practice of
syphilis serology and provides recommendations on the use of laboratory tests for
syphilis in UK diagnostic microbiology laboratories. The main recommendations are
summarised in a testing algorithm. Treponemal EIAs are an appropriate alternative
to the use of combined Venereal Disease Research Laboratories/rapid plasma reagin
and Treponema pallidum haemagglutination assay (TPHA) tests for screening for
syphilis. If a treponemal EIA is used for screening an alternative treponemal
test, such as TPHA, should be used for confirmatory testing. The fluorescent
treponemal antibody-absorbed test is probably best reserved for specimens giving
discrepant results. Such specimens may be referred to the PHLS laboratories that
provide confirmatory treponemal testing for reference testing and to facilitate
collection of surveillance data on what remains an important public health
problem.
PMID- 11014026
TI - Guidelines for the microbiological quality of some ready-to-eat foods sampled at
the point of sale. PHLS Advisory Committee for Food and Dairy Products.
AB - These guidelines for the microbiological quality of ready-to-eat foods represent
a revision and expansion of guidelines first published by the PHLS in September
1992 and revised in March 1996. The latest guidelines incorporate many of the
constructive comments received from food examiners and other microbiologists
within and outside the PHLS and from environmental health officers throughout the
United Kingdom. This document reviews the changes and the reasons they were made
and sets out the new guidelines. It also clarifies the role of food examiners in
interpreting the microbiological results of formal samples.
PMID- 11014027
TI - Outbreak of meningococcal disease in Rotherham illustrates the value of
coordination, communication, and collaboration in management.
AB - On New Year's Eve 1998, two teenagers from the same school in Rotherham died of
serogroup C meningococcal septicaemia. A third linked case occurred three days
later. Over eight days starting on New Year's Eve, a further five cases of
meningococcal disease arose across Rotherham district, four of whom were severely
ill with serogroup C meningococcal septicaemia. Intense media interest, high
levels of public concern, and anxieties caused by several 'false alarm' cases
added to the challenge faced by a small health district. This article describes
the epidemiology of the incident and policy decisions made, but focuses on the
operational aspects of outbreak management (coordination, communication, and
collaboration), an area often neglected in outbreak reports.
PMID- 11014028
TI - Carriage of Neisseria meningitidis in residents and staff at a residential home
for elderly people following a case of invasive disease.
AB - A study of the carriage of Neisseria meningitidis among staff and residents of a
'closed community' (a residential home for elderly people) was conducted after a
resident developed invasive meningococcal disease. All 39 other residents and 49
staff who worked at the home during the previous seven days were offered a throat
swab and 38 residents and 49 staff consented. Two residents (none in the index
case's social group) and one staff member were found to be carrying N.
meningitidis, all phenotypically distinct from the infecting isolate. Thus, all
four individuals carried different organisms and the index case was sporadic. Our
findings suggest that residents or staff in long stay residential settings where
a sporadic case occurs need not be offered meningococcal prophylaxis unless they
fulfil the existing definition of 'close personal contacts' of the case.
PMID- 11014029
TI - Optimising investigation of meningococcal disease to enhance surveillance.
AB - Efforts were made to implement guidelines for microbiologists in order to
optimise investigation and improve laboratory confirmation in children admitted
to hospital with suspected meningococcal disease. In 1998, 75% of diagnoses
(30/40) were confirmed microbiologically, compared with 51% (209/411) of cases
elsewhere in the West Midlands. Thirty-two of the children admitted to our
paediatric unit (80%) were investigated according to the guidelines; 94% of these
cases were laboratory confirmed. Microbiological confirmation of clinical
meningococcal disease is all the more important with the advent of mass
vaccination. Our study shows that implementation of guidelines for the
investigation of clinically suspected meningococcal disease improves the rate of
confirmation.
PMID- 11014030
TI - Outbreak of group C meningococcal infection affecting two preschool nurseries.
AB - Five cases of meningococcal infection caused by Neisseria meningitidis group C
type 2a, subtype P1.5, P1.2 occurred within six days. Two of the affected
children attended the same preschool nursery. The mother of two other children at
the nursery was affected, as were the mother and sibling of another child (not a
case) at the nursery. The 'sibling' case attended a different nursery. As the
situation evolved, the control aspects of the outbreak changed. Antibiotic
prophylaxis and vaccination were given to all staff and children attending both
nurseries, and to parents, siblings, and household contacts of all children
attending the first nursery.
PMID- 11014031
TI - Outbreak of tuberculosis associated with a church.
AB - Investigation of an outbreak of tuberculosis (TB) in a West Midlands health
district in 1999 revealed spread in an extended family network and to church
contacts. Within the family four cases of smear positive TB, four cases of smear
negative infection, and 14 cases requiring chemoprophylaxis were identified. One
of the infectious cases visited a local church on two occasions, which resulted
in a further 16 cases of infection including one case of tuberculous meningitis.
DNA fingerprinting of isolates from five culture positive cases indicated that
the same strain of Mycobacterium tuberculosis was responsible. This outbreak is a
reminder that while outbreaks of TB usually arise within households or family
networks, where close contact over extended periods provides more opportunity for
exposure, community outbreaks of TB can occur after only causal contact.
PMID- 11014032
TI - Limitations of national guidelines in the management of an outbreak of
tuberculosis.
AB - National guidelines offer no clear definition of a close (non-household) contact
of tuberculosis. The resulting lack of distinction between close and casual
contacts may lead to excessive screening in outbreaks of pulmonary tuberculosis
in the United Kingdom. Poor compliance with chemoprophylaxis suggests that
priority should be given to the follow up of high risk contacts, who should be
more clearly defined. A review of the management of a family outbreak of
tuberculosis illustrates the problem. Fifty-nine out of 213 non-household
contacts screened for infection had grade 3 and 4 Heaf reactions and none
developed clinical tuberculosis within one year. Three of the 59 did not attend
for chest radiography and a further 11 patients did not attend the outpatients
appointment offered. Twenty-three took chemoprophylaxis for three months, 14 did
not complete chemoprophylaxis, six (11%) declined it and two were offered x-ray
follow up.
PMID- 11014033
TI - Survival after diagnosis of AIDS among adults resident in the United Kingdom in
the era of multiple therapies.
AB - The epidemiology of HIV and AIDS in the United Kingdom (UK) has changed markedly
since highly active antiretroviral therapy (HAART) was introduced in 1996. HAART
including protease inhibitors has considerably improved survival from AIDS
diagnosis. The number of deaths of individuals with HIV infection in the UK,
reported within 12 months of the end of the year of death, have decreased between
1995 and 1998. Concurrently AIDS diagnoses, reported within 12 months of the end
of the year of diagnosis, have declined whilst diagnoses of HIV infection,
similarly reported, have risen. Data from 13,689 adult AIDS cases diagnosed up to
the end of 1996 were analysed. The overall median survival from AIDS diagnosis to
death was 19.3 months. Over 50% of the cases diagnosed in 1996 were alive at the
end of the survey therefore median survival exceeds 24 months, the maximum follow
up time for the cohort. The opportunity for receiving HAART was modelled in three
time periods: pre-multiple therapies (before September 1995), multiple reverse
transcriptase inhibitor therapy available (September 1995 to March 1996), and
multiple therapy including protease inhibitors available (April 1996 onwards).
Survival rates improved significantly among female heterosexuals and men who have
sex with men when multiple therapy including protease inhibitors became
available.
PMID- 11014034
TI - Evaluation of health information provided on the Internet by airlines with
destinations in tropical and sub-tropical countries.
AB - The travel industry is being called upon increasingly to provide health
information for its clients. Websites of all 73 international airlines with
tropical or sub-tropical destinations accessible via the International Air
Transport Association homepage were evaluated for the quality of their health
advice. Seven of the 73 homepages contained health information, six of which
addressed health problems that might be encountered when travelling to tropical
countries. Fifty-five of the 73 airlines had functional email addresses and were
asked for pre-travel health advice on malaria prophylaxis using a fictitious
scenario. Among the 25 airlines that replied, only half referred to malaria and a
third gave wrong information about malaria endemicity in the destination area.
The only two airlines that recommended a specific drug regimen correctly
reflected the medical situation described in our fictitious email. In general,
international airlines are not set up to provide health information.
PMID- 11014035
TI - Acceptability of health status questionnaire screening and vaccination among
Kosovar refugees.
AB - During 1999, following the war in Kosovo, thousands of Kosovar refugees were
received by different countries. The public health reception protocols for these
refugees varied widely between and within reception countries. We surveyed a
group of Kosovar refugees received in Bolton to assess the acceptability of
vaccination and health status questionnaire screening. We also examined the
refugees' opinions about the confidentiality of their medical history and their
willingness to take part in research. Fifteen out of 29 people responded. Most
respondents were happy with the interventions.
PMID- 11014036
TI - Investigation and management of sporadic gastrointestinal infections with
potentially Vero cytotoxin producing Escherichia coli in Scotland.
AB - Recognition of the potential of Escherichia coli O157 and other Vero cytotoxin
producing E. coli (VTEC) organisms to cause serious disease led to the
recommendation that all diarrhoeal stool specimens be examined for E. coli O157.
National guidelines exist for the testing and exclusion of cases and contacts of
VTEC infection. A survey was conducted to discover the extent to which these
recommendations are followed in Scotland by asking about current practices for
public health management of identified cases and laboratory investigation of E.
coli infection. About two thirds of Scottish health boards followed national
guidelines for testing and exclusion of cases and contacts of VTEC O157
infection. Most laboratories tested all diarrhoeal stools for E. coli O157 but
detection methods varied and a minority tested selected stools for non-O157 E.
coli serogroups. Standardisation of policies for laboratory testing of VTEC
infection would improve national surveillance. Adherence to evidence based
guidelines would standardise public health management of VTEC infections in
Scotland.
PMID- 11014037
TI - Factors associated with seeking emergency treatment following suspected chemical
contamination of a leisure pool.
AB - A leisure pool was evacuated when children complained of breathing difficulties,
cough, and eye irritation subsequently thought to be due to high chloramine
levels. The duration of the suspected contamination before the evacuation was
unknown: it was suggested that some subsequent attendances at accident and
emergency (A&E) departments had been prompted by news reports of the incident.
The extent and nature of symptoms, the cause of the incident, and the impact of
media reporting were investigated with the help of a postal questionnaire. One
hundred and thirty-seven people (all but six under 20 years of age) attended A&E
departments after the incident, most commonly with sore eyes (79%), cough (76%),
and sore throat (71%). The number of different symptoms was associated with the
length of time spent at the pool, but not with being present at the time of the
evacuation or with having heard about the incident on radio or television.
PMID- 11014038
TI - Outbreak of giardiasis in a daycare nursery.
AB - Seven children and one member of staff in a nursery in Kent became ill with
Giardia lamblia infection in three months in a nursery in Kent and three further
children were found to carry giardia. Person to person spread among young
children who were not toilet trained appeared to be responsible. All staff and
children were screened for infection, and the outbreak was controlled by
reinforcing hygiene measures, and treating microbiologically confirmed cases and
carriers with metronidazole.
PMID- 11014039
TI - Chickenpox increasingly affects preschool children.
AB - Between 1983 and 1998, age specific incidences of chickenpox derived from
consultations with general practitioners taking part in the Royal College of
General Practitioners Weekly Returns Service doubled in children aged 0 to 4
years, halved in children aged 5 to 14 years, and fell by almost a third in
adults aged 15 to 44 years. This downward shift in age of contracting chickenpox
may be a result of increased social contact between preschool children.
PMID- 11014040
TI - Hepatitis B immunisation of infants at risk.
AB - A retrospective cohort review survey assessed hepatitis B immunisation uptake in
at-risk infants over 4 years and a GP questionnaire identified the problems of
poor communication and uncertainty of responsibility for immunisation as barriers
to successful implementation of the immunisation programme. Incorporating
appointments for hepatitis B immunisation within the national child immunisation
recall system would help improve uptake but, in the meantime, a manual
appointment system could be incorporated within existing child immunisation
systems.
PMID- 11014041
TI - Needlestick injuries and hepatitis B virus vaccination in health care workers.
AB - An analysis of 2646 needlestick injuries in hospitals in the Greater Manchester
area between April 1992 and April 1999 was carried out. Ten per cent of members
of staff injured in these incidents had never been vaccinated against hepatitis B
virus (HBV) and 27% of those who had been vaccinated had no anti-HBs (< 10 IU/L).
Although few health care workers were at risk of transmission of HBV through
needlestick incidents in this study (0.6% (12/2084) of all source patients were
HBsAg positive; 9 HBeAg positive, 7 anti-HBe positive), the large number of
members of staff who were not protected from HBV infection indicates a need for
occupational health departments to reinforce HBV vaccination policies.
PMID- 11014042
TI - Pertussis vaccine efficacy in Birmingham.
PMID- 11014043
TI - Screening for chlamydia.
PMID- 11014044
TI - Procuring more organs for transplantation.
PMID- 11014045
TI - Bioinformatics from the perspective of the public health laboratory.
PMID- 11014046
TI - Production of standard operating procedures, algorithms, and guidance notes for
virology and serology.
PMID- 11014047
TI - Manual handling at work.
PMID- 11014048
TI - Outbreak of cryptosporidiosis in Northern Ireland.
PMID- 11014049
TI - National increase in Salmonella typhimurium DT104--update.
PMID- 11014050
TI - People focus on optimistic scenarios and disregard pessimistic scenarios while
predicting task completion times.
AB - Task completion plans normally resemble best-case scenarios and yield overly
optimistic predictions of completion times. The authors induced participants to
generate more pessimistic scenarios and examined completion predictions.
Participants described a pessimistic scenario of task completion either alone or
with an optimistic scenario. Pessimistic scenarios did not affect predictions or
accuracy and were consistently rated less plausible than optimistic scenarios
(Experiments 1-3). Experiment 4 independently manipulated scenario plausibility
and optimism. Plausibility moderated the impact of optimistic, but not
pessimistic, scenarios. Experiment 5 supported a motivational explanation of the
tendency to disregard pessimistic scenarios regardless of their plausibility.
People took pessimistic scenarios into account when predicting someone else's
completion times. The authors conclude that pessimistic-scenario generation may
not be an effective debiasing technique for personal predictions.
PMID- 11014051
TI - How serious are expressions of protected values?
AB - People think that some things that they value should be protected from trade-offs
with other things. For example, people think that no economic gain is great
enough to justify clear-cutting old-growth forest. The authors probed the
stability of these protected values (PVs) in several ways. Subjects were asked to
think of counterexamples, and this had some effect on PVs. Subjects were then
asked how they would resolve conflicts between 2 PVs. Resolutions did not differ
from those between other values, but subjects tended to feel that conflicts
between PVs did not occur in reality. Despite people's claims that PVs are
unchanged by variation in quantity, expression of PVs was reduced when the
magnitude or probability of the violation of a PV was smaller. In summary, PVs
appear to be labile and amenable to challenge. Despite earlier concerns, apparent
PVs may not always preclude the use of valuation measures in cost-effectiveness
analysis or negotiated agreement on controversial issues.
PMID- 11014052
TI - Asking questions can change choice behavior: does it do so automatically or
effortfully?
AB - The present research uses a technique that permits unique estimation of both
automatic and effortful processes in the question-behavior link. Results show
that individuals asked to report behavioral intent (vs. those not asked) are more
likely to choose options that are highly accessible and positively valenced,
regardless of cognitive resources available at the time of processing. This
suggests that the effect of intent questions on subsequent behavior is primarily
the result of automatic, as opposed to effortful, processing. Practically, this
suggests that efforts to debias this robust effect need to affect nonconscious
processes and adjust for the automatic impact of being asked an intention
question on respondents' behavior.
PMID- 11014053
TI - Process versus content in eyewitness metamemory monitoring.
AB - Three studies (Ns = 200, 135, and 187 college undergraduates) contrasted process
versus content accounts of eyewitness metamemory monitoring. Subjective
vividness, a cue related to memory content, was a better predictor of confidence
and accuracy than were cues related to the retrieval process. Participants who
were asked to recall, rather than recognize, event details displayed greater
insight into accuracy, primarily because vividness was a more valid accuracy cue
under recall conditions. Results reinforce the value of recall-based protocols
for eliciting eyewitness testimony and suggest some specific conditions (e.g.,
yes-no recognition) under which investigators should be especially cautious in
relying on confidence to infer accuracy. In addition, results point to a general
framework for understanding moderating effects on eyewitness metamemory accuracy.
PMID- 11014054
TI - When to inspect? Recurrent inspection decisions in a simulated risky environment.
AB - Participants scheduled inspections to detect costly events for which they were
repeatedly at constant risk (probability of event onset) within a computerized
environment. They were responsive to risk variations, conveyed either in advance
or by experience with inspection outcomes, although experiencing unannounced
increases in risk affected inspections more than experiencing unannounced
decreases. Participants responded to variations in cost (time varying or fixed)
when the effects were made perceptually salient. Compared with a normative model
(R. L. Klatzky, D. M. Messick, & J. Loftus, 1992), some conditions showed near
optimal inspecting or had flat payoff functions that tolerated observed
departures from optimal performance. Costly departures occurred particularly when
combined cost and risk levels caused optimal responses to be extreme (always or
never inspect). Results assess people's processing of relevant variables and
indicate circumstances in which they may set substantially nonoptimal inspection
schedules.
PMID- 11014055
TI - The impact of sleep deprivation on decision making: a review.
AB - Few sleep deprivation (SD) studies involve realism or high-level decision making,
factors relevant to managers, military commanders, and so forth, who are
undergoing prolonged work during crises. Instead, research has favored simple
tasks sensitive to SD mostly because of their dull monotony. In contrast, complex
rule-based, convergent, and logical tasks are unaffected by short-term SD,
seemingly because of heightened participant interest and compensatory effort.
However, recent findings show that despite this effort, SD still impairs decision
making involving the unexpected, innovation, revising plans, competing
distraction, and effective communication. Decision-making models developed
outside SD provide useful perspectives on these latter effects, as does a
neuropsychological explanation of sleep function. SD presents particular
difficulties for sleep-deprived decision makers who require these latter skills
during emergency situations.
PMID- 11014056
TI - What's new in the treatment of cerebrovascular disease?: an endovascular
perspective.
AB - Surgical therapy currently allows for the correction of many pathologic
conditions affecting the vasculature of the central nervous system. Recent
advances in technology have given the cerebrovascular specialist further options
in the minimally invasive sphere. Endovascular techniques, complimentary to
surgery in some conditions, are poised to replace conventional open surgery in
others. A review of current interventional radiological procedures for the
treatment and prevention of ischemic and hemorrhagic stroke are herewith
presented.
PMID- 11014057
TI - Physician-based tobacco dependence interventions: review and clinical practice
recommendations.
PMID- 11014058
TI - Ten commandments of risk management.
PMID- 11014059
TI - MSMA joins Medem to provide members and their patients with authoritative and
secure online information and communications.
PMID- 11014060
TI - Putative peripheral neuropathy in suckling piglets.
AB - Over a period of almost 2 years, a progressive motor disturbance was found to
occur in 20-50% of the litters of both primiparous and multiparous sows in a
large pig herd of 1000 sows. The motor disturbance sometimes affected the entire
litter; however, in most cases only a few piglets per litter were affected. The
clinical signs appeared at 3-5 days of age and consisted of difficult movement
followed by anteflexion or retroflexion of the tarsal joints or 'rabbit-like
posture'. Subsequently, primarily after weaning, inflammatory and necrotic
lesions developed on the paralysed limbs as a result of secondary infections of
injuries. The tibial nerve and the common fibular nerve of recently affected (5-
to 6-day-old) piglets showed degeneration, demyelination and necrosis of some of
the nerve fibres, accompanied by restorative changes in more chronic cases. The
central nervous system, bones, skeletal muscles, tendons and joints showed no
lesions that could have accounted for the symptoms of motor disturbance.
Aetiological investigations excluded the possibility of lead, copper and cadmium
toxicity. Vitamin B2 administered orally at 1 day old proved to be ineffective.
The disease did not develop in piglets of sows kept at another farm under the
same management and fed a diet prepared according to an identical formula from
the same ingredients as those used on the affected farm, but with no milk whey
added. This raised the suspicion of triaryl phosphate (TAP) poisoning, but this
was found not to be the cause of the disease. New boars had not been brought to
the farm in the year preceding the onset of disease, and the disease could not be
linked to a specific boar or boar line. The aetiology of the disease has remained
unclear.
PMID- 11014061
TI - Characterization of lesions caused by a South American virulent isolate
('Quillota') of the hog cholera virus.
AB - In this study, macroscopic and histopathological lesions produced by a virulent
South American isolate ('Quillota') of hog cholera virus were studied. The virus
was inoculated in doses of 10(5)TCID50 in each of 35 pigs of 20 kg live weight.
The animals were slaughtered from 4 to 18 days post-inoculation. The presence of
virus antigens in lymphatic tissue was confirmed by both direct
immunofluorescence and Avidin-Biotin-Peroxidase techniques in formalin-embedded
tissue samples. Histological sections were stained with haematoxylin-eosin and
Mallory's phosphotungstic acid haematoxylin methods. The 'Quillota' isolate used
in this study caused a disease characterized by vascular lesions (splenic
infarcts, haemorrhages in the lymph nodes and the urinary system and disseminated
microthrombosis), and necrosis of lymphocytes, particularly in the B-areas of the
lymphoid organs, lesions that are characteristic of the acute form of the
disease. Other lesions observed were a non-purulent meningoencephalitis, the
necrosis of the epithelial cells of tonsils, the presence of fibrin nets in the
red pulp and a marked thickening of the alveolar septa.
PMID- 11014062
TI - The modification of fluorescent antibody virus neutralization (FAVN) test for the
detection of antibodies to rabies virus.
AB - The fluorescent antibody virus neutralization test (FAVN) for the detection of
antibodies against rabies virus was modified by using a monoclonal anti-rabies
antibodies and peroxidase anti-mouse conjugate instead of a fluorescent anti
rabies conjugate. The results were read on an automatic multi-channel
spectrophotometer. A total of 182 serum samples from dogs were tested by both the
original and modified FAVN methods and the results were compared. Good
correlation was found between the two tests. Practically, the modified FAVN test
was quicker and could be used for a larger number of samples.
PMID- 11014063
TI - Immunoglobulin G class identification from wild ungulates by cross-reactivity
with antisera to domestic animals.
AB - Seven species of Spanish ungulates were tested for the presence of homologous
immunoglobulin G (IgG) with a gel-diffusion test using bovine, ovine, caprine and
porcine IgG antisera. Homologous ovine and caprine IgG were detected in sera from
chamois (Rupicapra pyrenaica), Spanish ibex (Capra pyrenaica hispanica), mouflon
(Ovis orientalis musimon), red deer (Cervus elaphus), fallow deer (Dama dama) and
roe deer (Capreolus capreolus). Homologous porcine IgG was detected in wild boar
(Sus scrofa) serum. Immunoelectrophoretic assays were performed to compare the
electrophoretic mobility of IgG from domestic and wild species.
PMID- 11014064
TI - Isolation of Candida rugosa from turkeys.
AB - The present study describes the isolation of Candida rugosa from young turkeys
that died 10 days after the end of a therapeutic treatment for a recent outbreak
of coccidiosis. Candida rugosa was isolated from the digestive tract of all the
birds examined. This isolation is the first in turkeys and corroborates the fact
that C. rugosa is an opportunistic yeast which circumvents host defences when
other predisposing factors are present.
PMID- 11014065
TI - The sensitivities of various erythrocytes in a haemagglutination assay for the
detection of psittacine beak and feather disease virus.
AB - The erythrocytes of various species were tested in psittacine beak and feather
disease (PBFD) virus haemagglutination (HA) and haemagglutination inhibition
assays to determine which are suitable for use in these assays. HA activity was
observed for erythrocytes of the salmon-crested cockatoo, the sulphur-crested
cockatoo, the umbrella cockatoo, the goffin's cockatoo and the cockatiel, with
differences amongst individuals within species, but not for erythrocytes of
humans, the pig, the guinea pig, the chicken, the goose, the rose-ringed parakeet
or the budgerigar. Anti-PBFD virus rabbit sera inhibited the virus-induced
agglutination of erythrocytes, confirming the specificity of HA activity. This
suggests that selection of suitable psittacine species as well as suitable
individuals within a species is necessary when obtaining erythrocytes for the
PBFD virus HA assay.
PMID- 11014066
TI - Effectiveness of doxycycline in the prevention of an experimental infection with
Actinobacillus pleuropneumoniae in pigs.
AB - The effectiveness of medication with doxycycline in feed in the control of
pleuropneumonia in pigs was tested using an Actinobacillus pleuropneumoniae
serotype 1 aerosol challenge model. Two groups of 10 animals were used for the
challenge, a 'medicated group' and an 'unmedicated group'. A third group of four
animals was used as a 'control group'. Pigs from the medicated group were
provided with feed containing 250 p.p.m. doxycycline (HIPRAMIX/DOXI) for 8
consecutive days and were challenged on the fifth day of treatment. No clinical
signs were observed in pigs from the 'control group'. Four animals from the
'unmedicated group' died within the first 48 h after challenge with clinical and
lesional evidence of an acute form of pleuropneumonia. Clinical signs of animals
surviving the first 48 h were progressively less severe and showed lesions
similar to those described for subacute-chronic forms of the disease. However,
only one animal from the 'medicated group' showed clinical signs of a chronic
form of pleuropneumonia. Reisolation of A. pleuropneumoniae was more evident from
lung tissues of animals fed the doxycycline-free feed (70%), coinciding with the
presence of both acute and subacute lesions. However, the micro-organism could be
reisolated from only one animal which belonged to the 'medicated group'. It is
concluded that the treatment of pigs with 250 p.p.m. doxycycline (HIPRAMIX/DOXI)
prevents disease caused by A. pleuropneumoniae.
PMID- 11014067
TI - Influence of antibiotics used as feed additives on the immune effect of
erysipelas live vaccine in swine.
AB - To investigate the influence of antibiotics used as feed additives on the immune
response to erysipelas live vaccine, the pig inoculation test was applied.
Avilamycin, oxytetracycline quaternary salt, enramycin, virginiamycin and tylosin
phosphate were selected as test antibiotics. Five experimental feeds containing
each antibiotic at the highest concentration permitted for feed additives in
Japan, and the basal diet lacking antibiotics were examined. Twenty-nine pigs
were divided into six groups. At first all the groups were fed with the
antibiotic-free basal diet for 7 days, and then each group received the
experimental feeds. On the 14th day after feeding with test feeds all the pigs,
except for one control pig in each group, were immunized with the vaccine and all
the pigs were then challenge-exposed to a virulent strain of Erysipelothrix
rhusiopathiae 14 days after vaccination. The clinical response was observed every
day for 14 days. In all the groups, most of the vaccinated pigs did not develop
any clinical signs of acute erysipelas after the challenge exposure, whereas non
vaccinated control pigs died or showed severe generalized erythema with profound
depression and anorexia. No differences in the protection against the challenge
exposure were observed among the groups. Therefore, the present results suggest
that these selected antibiotics would not interfere with the immune effect of the
vaccine if given at the usual concentrations used for feed additives.
PMID- 11014068
TI - Varying effects of infections with Mycoplasma hyopneumoniae on the weight gain
recorded in three different multisource fattening pig herds.
AB - Pigs in three specialized fattening herds were studied with respect to the effect
of infection with Mycoplasma hyopneumoniae on weight gain. Individual pigs were
weighed four times at 4-week intervals during the fattening period and their
daily weight gain over the rearing period was calculated. A blood sample was
collected on each weighing occasion and analysed for the presence of antibodies
to M. hyopneumoniae. The lungs of the principals were inspected at slaughter and
the extent of pneumonic lesions was registered by a specially developed technique
that has been proven to warrant a high degree of repeatability. No serum
antibodies to M. hyopneumoniae were detected in one of the herds, and no
pneumonic lesions were recorded at slaughter in that herd. In the other two
herds, the prevalence of pigs with serum antibodies to M. hyopneumoniae increased
from 6 to 54% and from 31 to 81%, respectively, during the fattening period. The
prevalence of pneumonic lesions at slaughter in these herds was higher the later
the pigs seroconverted. On the other hand, the extension of the lung lesions
tended to be higher among pigs that seroconverted early during the rearing
period. Infections with M. hyopneumoniae acquired early during the rearing,
presumably strengthened by secondary infections and environmental errors, was
found to decrease the daily weight gain of the pigs. However, even non
complicated M. hyopneumoniae infections acquired late in the fattening period
were associated with reduced daily weight gain. That growth reduction was
estimated to be at least 60 g (about 6%) after adjusting for herd, pen, initial
weight and sex.
PMID- 11014069
TI - Occurrence of chlamydiae in the genital tracts of sows at slaughter and their
possible significance for reproductive failure.
AB - The aim of this study was to investigate further the role of chlamydiae as
pathogens in the genital tracts of sows at slaughter. Genital tracts of 101
randomly selected sows were collected and specimens of genital tract
localizations were systematically examined for chlamydiae using
immunohistochemistry and PCR. In the genital tracts of 10 sows, Chlamydia
psittaci DNA was detected by PCR, and was further typed as 'serotype 1' in nine
cases and as avian strain 6 BC in one animal. However, all specimens examined by
immunohistochemistry were negative for chlamydiae. Pooled samples of scalding
tank water were additionally investigated for 95 animals. Of these samples, 63.2%
contained chlamydial DNA, mostly C. trachomatis, and in one sample C. psittaci
'serotype 1'. Although in most cases contamination through influx of faecally
contaminated scalding water is a possible reason for the positive PCR results in
the genital tract, latent infection cannot be excluded. In conclusion, the
results obtained suggest that chlamydiae are of no or only minor importance in
the examined group of Swiss breeding sows. Nevertheless, the role and
significance of chlamydiae as pathogens in porcine reproductive disorders remain
unresolved and require further investigation.
PMID- 11014070
TI - HC2000 at Harrogate. Health informatics proceeds with caution.
PMID- 11014071
TI - HIPAA 2000 Conference report. HIPAA is heating up.
PMID- 11014072
TI - Health information on the Internet: let the viewer beware (caveat viewor).
PMID- 11014073
TI - The granting game: Part II. How to love NIH form 398 and get that grant.
PMID- 11014074
TI - Buy software or "pay-per-view": the ASP option.
PMID- 11014075
TI - The Yale Center for Medical Informatics: clinical, neuro- and genomic
informatics.
PMID- 11014076
TI - A paradigm shift in healthcare. From disease management to patient-centered
systems.
PMID- 11014077
TI - New modalities complicate the legal balance.
PMID- 11014078
TI - The "bank of health". A model for more useful patient health records.
PMID- 11014079
TI - Behavioral health information systems. Evaluating readiness and user acceptance.
PMID- 11014080
TI - Aortic dissection.
AB - Acute and chronic aortic dissection is described in terms of diagnostics,
surgical indications and present day operative treatment. The need for prompt
decision making and intervention is highlighted. The results to be expected from
surgery are outlined.
PMID- 11014081
TI - New criteria for the diagnosis and treatment of atrioventricular node reentrant
tachycardia.
AB - The authors describe a new elecrocardiographic criterion to diagnose
atrioventricular node reentrant tachycardia, review the electrocardiographic and
electrophysiological diagnosis of this tachyarrhythmia and analyse the results of
catheter ablation of fast versus slow pathway, selecting the fast pathway
whenever the induction of atrioventricular node reentrant tachycardia is
performed only after pharmacological maneuvers. The high specificity for
atrioventricular node reentrant tachycardia of the criterion characterized by the
absence of ST-segment depression found in left precordial leads from V4 to V6
suggests the need to include it in electrocardiographic algorithms for the
differential diagnosis of tachycardias with a narrow QRS complex. The high
primary and final success rates of catheter ablation obtained after a therapy
stratification based on induction criteria, emphasize the use of the fast pathway
ablation as a first option in selected cases and for the treatment of
recurrences.
PMID- 11014082
TI - Differential diagnosis of chest pain in an emergency department: the value of
homocysteinemia as a diagnostic marker.
AB - Only 20 to 45% of patients (pts) admitted to an emergency department (ED) with
chest pain (CP) have a cardiac ischemic CP (ICP). Apart from the need for a rapid
detection of ICP cases, it is important to avoid discharging patients with false
negative ICP. We studied the capability of plasma homocysteine (Hcy) values to
improve the differential diagnosis (DD) in patients admitted to an ED with CP.
PATIENTS: 125 patients, 80 males, mean age 61 yrs (25-96 yrs), 75 (60%) without
prior atherosclerotic cardiovascular disease (ACVD), consecutively admitted to
the ED with CP which was not immediately clear. Definitive diagnosis: ICP-58
patients (46%); non-ischemic (non-ICP)--64 patients (54%). METHOD: Hcy was
measured on admittance (fasting state not required), by means of a fluorescence
polarization enzyme immunoassay (IMx, Abbott); at real conditions, the results
were obtained within 2 hours (but not displayed). RESULTS: 1) Hcy (mumol/L) =
10.9 +/- 5.4 (non ICP without prior CDAV); 13.9 +/- 7.7 (ICP). 2) Hcy > or = 15.0
mumol/L in patients without prior ACVD: 5 patients (9%) with non ICP, 8 patients
(38%) with ICP--p < 0.01; RR = 2.9 (95% CI = 1.2-7.1); positive value = 62%;
negative predictive value = 79%. CONCLUSION: In patients without ACVD, Hcy may
contribute to improve DD of equivocal CP, namely: 1) before a normal or non
diagnostic ECG and negative ischemia markers, Hcy > or = 15.0 mumol/L will imply
additional cardiological investigation in the ED; 2) Hcy < 15.0 increases the
liability of a non-ICP diagnosis.
PMID- 11014083
TI - Homocysteinemia in the emergency department.
PMID- 11014084
TI - Blood pressure in pediatric years (8-13 years old) in the Oporto region.
AB - The early detection and treatment of primary and secondary hypertension in
children may contribute to the improvement of health later in life. During
childhood, the occurrence of arterial hypertension should be understood as a risk
situation, even if the clinical signs of the disease are not obvious.
Comparatively to other populations, only few epidemiological studies exist in
Portugal to be used as clinical references. Thus, the aim of this work was to
study the distribution curves of 30, 60 and 90 percentiles of systolic blood
pressure (SBP) and diastolic blood pressure (DBP), related to age, height, and
weight. To define the "cut off points" of hypertension in our population, we
estimated the 95 percentile of SBP and DBP. This is a cross-sectional study. The
sample consisted of 474 children (242 boys and 232 girls), aged 8 to 13 years
old, randomly selected in 30 different schools of the Oporto region. Weight,
height and body mass index were evaluated as anthropometric reference values and
blood pressures, SBP and DBP, were measured at rest. The results revealed a
gradual increase in blood pressure values with age, height and weight. We found
significant correlations (p < or = 0.05; p < or = 0.01) between SBP and DBP to
the variables height, weight and blood mass index in both sexes. Multiple
regression analysis showed that weight and age explain significantly (p < or =
0.01) the variation of SBP in both sexes. Related to DBP, in males and females,
only age accounted significantly for the amount of variance. In conclusion, the
present study pointed out the need to associate the SBP and DBP values to the
age, weight and height of the subjects, mainly in boys. This work stresses the
need for SBP and DBP percentile tables related to age, to weight and to height,
for the Portuguese population, particularly for pediatric ages.
PMID- 11014085
TI - [Diagnosis of paradoxal and concomitant pulmonary thromboembolism with
transesophageal echocardiography: a clinical case].
AB - There is some controversy regarding the indications for transesophageal
echocardiography in patients with suspected systemic embolism. The present case
report refers to a 65 year old male admitted to the hospital for ischemic acute
cerebrovascular accident, which was confirmed by cerebral computerized
tomography. A transthoracic echocardiogram was performed showing right atrial and
ventricular dilatation. A transesophageal echocardiogram was also performed to
exclude thromboembolism and clarify dilatation of the right cavities. Mild
spontaneous echocontrast was present in the left atrium without images of
thrombus; an interatrial septal aneurysm with patent foramen ovale was found with
right to left flow; an image compatible with a very mobile, large, proximal
thrombus in the main pulmonary artery was observed. A venous duplex scan was
performed, demonstrating venous thrombosis in the right popliteal and femoral
veins. Pulmonary arteriography showed a large thrombus in the right pulmonary
branch extending to the median lobe and a smaller thrombus in the left pulmonary
branch. Apparently, the patient had no predisposing factors for thromboembolism.
Full-dose heparin was started followed by oral anticoagulation. An inferior vena
cava filter was implanted. At hospital discharge the pulmonary thrombus had
disappeared and the right cardiac cavities had returned to normal size. The
interatrial aneurysm had disappeared and foramen ovale was no longer patent.
After 36 months of clinical follow up on oral anticoagulation, the patient
remains asymptomatic without neurological sequelae nor respiratory distress.
PMID- 11014086
TI - Severe mitral regurgitation due to a leak of a mitral ring--an echocardiographic
view.
PMID- 11014087
TI - Myocarditis due to influenza virus complicated by intravascular coagulopathy.
PMID- 11014088
TI - Cardiopulmonary resuscitation by chest compression alone or with mouth-to-mouth
ventilation.
PMID- 11014089
TI - [Research in axillary lymphatic metastasis...which techniques for which material?
What is at stake?].
PMID- 11014090
TI - [Lymph node micrometastasis? Reflections on their definition, demonstration,
significance and conclusions to be drawn].
PMID- 11014091
TI - [The place of surgery in the treatment of advanced localized, recurrent and
metastatic breast cancer].
AB - In the multidisciplinary treatment of locally advanced and metastatic breast
cancer, aggressive surgical options can be chosen in selected cases. They may
allow: survival to be prolonged by the resection of metastases (liver, ovary,
lung), symptomatic treatment (bone pain, local recurrence, infiltration of the
chest wall), prevention of potentially disabling complications (pathologic
fractures, medullary compression), exclusion of another tumoural or non tumoural
diseases. The decision to perform surgery has to be discussed between the surgeon
and the oncologist so as to optimise its timing. Surgical treatment can follow
induction therapy or can precede chemo- or hormonotherapy.
PMID- 11014092
TI - [Sentinel lymph node biopsy in breast cancer: the Lausanne experience].
AB - A total of 40 patients (mean age 51 yrs; 36-89 yrs) with clinically T1-T2(< 3
cm)N0M0 breast cancer underwent sentinel node (SN) mapping with radioactive
tracer (99mTc) injection only in 21 patients, with Patent blue V in 1 patient, or
with both techniques in 19 patients. The preoperative injection of 99mTc (20-40
MBq) was followed by lymphoscintigraphy. A handheld gamma probe was used to
detect the SN in the operative room. A lumpectomy and an axillary dissection were
performed in all the patients. SNs could be identified in 39/40 patients,
resulting in a sensitivity of 98%. Successful localization of the SNs was
accomplished by isotope only in 19/20 patients, by blue dye only in 1/1 patient,
and by both methods in 19/19 patients; in 2 of these 19 patients, SNs were
identified by blue dye only. Axillary metastases were found in 12/40 patients
(30%), the SN being the only nodal metastasis in 8/12 patients (75%). Six of
these 12 patients (50%) had only evidence of micrometastasis. Negative SNs on
serial sections stained with hematoxylin-eosin (H&E) were evaluated with
cytokeratin immunostain (C11). In all cases of negative SNs the remaining
axillary nodes were also free of tumor, resulting in a negative predictive value
of 100%. We conclude that SN mapping is a highly accurate method for staging the
axillary node status in breast cancer patients. Optimal localization is achieved
by the combination of injection of 99mTc-colloid and blue dye as evidence by the
cases of positive SN identified by only one of both methods.
PMID- 11014093
TI - [Aromatase inhibitors in the treatment of breast cancer].
PMID- 11014094
TI - [Organized screening for breast cancer: the Vaud experience].
PMID- 11014095
TI - [Chemoprevention of breast cancer: a hope justified?].
AB - Chemoprevention of breast cancer, a dream? In one American study (National
Surgical Adjuvant Breast and Bowel Project, NSABP-P1) tamoxifen decreased the
incidence of invasive and non-invasive breast cancer, whereas in two English and
Italian studies, it did not reduce this risk. Differences in the study population
for the trials may underly these conflicting findings. New drugs, the SERMs, may
be more promising.
PMID- 11014096
TI - [What's new in hormone replacement therapy for postmenopausal women? I.
Advantages of hormone replacement therapy (HRT)].
AB - Different cohort studies have shown that HRT decreases the risk of cardio
vascular (C-V) disease and the risk of bone fracture by 30 to 50%. The only
controlled study (HERS study) did not show any benefit of HRT with estradiol and
medroxyprogesterone (MPG) in secondary prevention. The beneficial effect of
estrogens on coronary dilatation and on HDL cholesterol could be attenuated by
some progestogens such as MPG but not by nomegestrol acetate. In this framework,
the comparative metabolic effects of different progestogens and tibolone are
described in this article. The effects of estrogens on mood and of androgens on
libido are discussed. The preventive effect of estrogens on osteoporosis and on
Alzheimer disease is compared to other nonhormonal treatments.
PMID- 11014097
TI - [What's new in hormone replacement therapy of postmenopausal women? II. Risks of
hormone replacement therapy (HRT)].
AB - A 50 year old woman has a 10% lifetime risk of developing a breast cancer.
Depending on the duration of the treatment, HRT can increase this risk by 30 to
45%. The risk of endometrial cancer, which affects 2.3% of women, is increased
even if sequential progestogens are given together with estrogens. The risk of
venous thrombosis is increased 3 times. The occurrence of ictus is not modified
by HRT. On the other hand estrogens may prevent the abdominal deposit of fat. The
cancer risks associated with HRT must be balanced against their protective
effects on cardio-vascular (C-V)diseases. In untreated women, mortality due to C
V disease is 39% whereas mortality due to breast cancer is 3% and only 0.3% for
endometrial cancer. This article discusses also the possibility of HRT and of non
hormonal treatments in patients with previous breast cancer.
PMID- 11014098
TI - [Interleukin-1 inhibitors: a new alternative for the treatment of rheumatoid
polyarthritis].
PMID- 11014099
TI - [Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in ORL
and pulmonary oncology].
PMID- 11014100
TI - [St. John's wort--scientific tests. Report of an expert workshop in Berlin].
PMID- 11014101
TI - [Disability evaluation: support from the model of complexity].
PMID- 11014102
TI - [Image of the month. Renal vein thrombosis in the neonatal period].
PMID- 11014103
TI - [How I treat...decubitus ulcers surgically].
AB - Although pressure sores occur frequently during the evolution of paraplegic
patients, they can present in patients confined to bed or in casts. Ischiatic,
sacral and trochanteric sores are the most frequent. For stade III & IV lesions
surgical excision followed by a coverage with healty tissue remain the only right
principle. Usually, flap transfert meats these requirements. However, the
selection of the surgical procedure and the post-op care are the main factors for
a successful treatment.
PMID- 11014104
TI - [Clinical case of the month. Abdominal wall hematoma and macroscopic hematuria in
a 95 year-old patient].
AB - We report the case of a 95 year-old female patient who died from hypovolemic
shock caused by severe hematuria and abdominal hemorrhage. The necropsy
demonstrated a primary signet-ring cell adenocarcinoma of the urinary bladder.
The diagnosis, prognosis and histogenesis of this uncommon tumor are discussed.
PMID- 11014105
TI - [Medical-legal aspects in sexual assault matters].
AB - The examination of a victim of sexual acts represents an important activity in
forensic medicine, so quantitatively that by his contribution to truth
demonstration. Either ponctual or repeated facts, this investigation, required by
judicial authorities, necessitates a big availability towards victims, an
anatomical thorough knowledge in particular of various aspects of hymen as well
as samples of high quality. This article lays emphasis on basic points for the
good accomplishment of this forensic examination.
PMID- 11014106
TI - [Bronchial morphologic modification in asthma].
AB - Asthma is an inflammatory disease of the airways clinically characterised by
recurrent bronchial obstructions at least partially reversible. Recent
epidemiologic data suggest that asthmatics have an increased rate of decrease of
their expiratory volumes during life. This irreversible lung function impairment
is associated with fundamental structural changes of the bronchial wall in terms
of conjunctive tissue and smooth muscle composition. We describe these changes
and explore the different mechanisms proposed to explain these structural
modifications. We also review their consequences in terms of bronchial physiology
and their potential influence on bronchial hyperresponsiveness.
PMID- 11014107
TI - [Hydroxyurea and HIV infection].
AB - Hydroxyurea is an anticancerous product, used recently in the treatment of HIV-1
infection thanks to its inhibitory action in viral replication, potentialization
of the nucleosides activity (particularly ddI or didanosine) and its cytostatic
properties on CD4 and CD8 lymphocytes. Many studies showed its efficiency, as
further drug, in initial regimen of a tritherapy (containing ddI) and salvage
therapy. The dosage of 500 mg bid seems tolerated well by adults, and 20 mg/kg by
children. Long-term tolerance remains unknown. With ddI, it could be proposed in
developing countries.
PMID- 11014108
TI - [The IGF system: summary and recent data].
AB - We are entitled to state that our knowledge about the IGF system has literally
exploded in the last years. Having been considered for some time merely as
trophic and mitogenic factors, the IGFs now appear as molecules essential for the
differentiation of many cell types, and even more so, as powerful protective
agents for the nervous and the cardiovascular systems. However, these properties
so beneficial in normal physiological conditions, are subverted by the cancerous
cells who use them to extend their life span and resist therapy. The IGFs did not
live up to expectations in the treatment of diabetes; however, today their
capacity to improve the condition of patients suffering from severe neurological,
renal or muscle diseases is tested. The IGF system might also be targetted by the
anticancer treatments. In the following paper we have briefly summarized our
knowledge on the IGF system, and presented in more detail the recent data.
PMID- 11014109
TI - [250 years ago "L'Homme machine" was published. La Mettrie (1709-1753). The
origins of medical materialism].
AB - Some 250 years ago, the publication of "L'Homme machine" established the fact
that human body and brain functioning was to be approached by human study just as
like as physics or chemistry.
PMID- 11014110
TI - [How I investigate...fetal pathology. Technique and value of the fetal and
placental examination and the perinatal autopsy].
AB - Fetal pathology is a recent field in pathological anatomy, knowing at the present
time an important technical and theoretical development. However, it is still
insufficiently used to resolve cases of fetal death in utero, or peripartum or
perinatal. In this paper, we describe the basics and the techniques used during
the fetal examination. We underline the values of these techniques for the
understanding of failures of pregnancy and for orientation of the genetical
advice for future pregnancies.
PMID- 11014111
TI - [Pharma-clinics. The drug of the month. Rofecoxib (Vioxx)].
AB - Rofecoxib (Vioxx, Merck Sharp & Dohme) is a potent and selective inhibitor of the
COX-2 isoform of cyclooxygenase which is used as a nonsteroidal anti-inflammatory
drug (NSAID). It is indicated in the symptomatic relief of pain due to
osteoarthritis. The initial oral dosage of rofecoxib is 12.5 mg once daily in
adults, and this dose may be increased up to a maximal dosage of 25 mg once daily
if necessary. Its clinical efficacy seems to be similar to that of other NSAIDs
at maximal recommended dosages, but its safety profile, especially
gastrointestinal tolerance, is much better because of the COX-2 selectivity.
Ongoing clinical trials are performed in patients with rheumatoid arthritis.
PMID- 11014112
TI - [Clinical study of the month. The ALLHAT study: a recommendation for prudence in
the use of alpha-blockers for the treatment of hypertension].
PMID- 11014113
TI - [What's new in the domain of obesity?].
AB - We will briefly comment on some interesting topics presented at the 10th European
Congress on Obesity (ECO, Antwerp, Belgium, 24-27 May 2000). Special attention
has been focused upon: 1) the multi-endocrine function of the adipocyte cell; 2)
the role of gene-environment interactions; 3) the regulatory mechanisms of energy
balance; 4) the neuroendocrine hypothesis for the development of visceral
adiposity; 5) the numerous complications associated with obesity, more
particularly type 2 diabetes; and, finally, 6) obesity prevention, especially in
childhood, and new pharmacological perspectives for the treatment of obesity.
PMID- 11014114
TI - [Rationing in health care: the elderly as victims?].
PMID- 11014115
TI - [Rationing: the royal path in health care?].
PMID- 11014116
TI - [Ethically fair accessibility in health care].
PMID- 11014117
TI - [Political considerations in discussing health care rationing].
PMID- 11014118
TI - [Rationing in the hospital: realities and decision pathways].
PMID- 11014119
TI - [Age as a rationing criterium?].
PMID- 11014120
TI - [Allocation of donated organs for elderly patients].
PMID- 11014121
TI - [Rational service allocation instead of threatened rationing of requested
services for the elderly. The example of neurorehabilitation].
PMID- 11014122
TI - [Dementia, a rational rationing criterium?].
PMID- 11014123
TI - [Decision making in dementia--from the viewpoint of affected relatives].
PMID- 11014124
TI - [Attitude of seniors to rationing in health care--before and after a lecture
series].
AB - Prior to the first lecture in the public series of lectures entitled "Rationing
of Health Care: Are Elderly the Victims?" and before a lecture given to a Senior
Citizens Association on the same subject, all participants were polled. The
polling was repeated at the end of the lecture series. The initial participation
totalled 69 with two-thirds women, average age 64 years (50% were from the health
care or social welfare sector), and 57 retired business people (50% women). At
the end, there were 45 listeners (average age 65 years), with 30 taking part in
both surveys. The majority believed that rationing is already taking place, only
1/6 rejected such measures in principle. When asked, nearly all those surveyed
were in favor of quality of life after treatment and life expectancy as criteria
for the right to medical services. Personal criteria, such as nationality, social
role, self-related causes and calendar age were rejected by the majority,
although less clearly by the business people than by the general participants.
This rejection became more marked after the lecture series. Those surveyed gave
various specific judgements on decisions about the complex allocation of
resources and favored decision-making by patients themselves unless they were
senile. A large minority were opposed to very elderly patients making decisions
themselves, even if they were not senile. CONCLUSION: The elderly persons polled
demand that all rationalization measures be exploited before rationing is
implemented. Rationing criteria must be of a universal nature and borne by the
general public.
PMID- 11014125
TI - [Proposals for rationing in public health from the viewpoint of the elderly].
PMID- 11014126
TI - [What is your diagnosis? Large-cell bronchial carcinoma cT3 N2-3 M0].
PMID- 11014127
TI - [Standard hepatitis B therapy].
AB - Standard treatment of chronic hepatitis B virus infection includes the use of
interferon-a and antiviral nucleoside analogues, alternatively. In general, in
patients with hepatic inflammatory activity, low viral titers and HBe positive
wild-type infection interferon leads to a long-term seroconversion rate of about
30-50%. However in patients with advanced liver disease, in interferon non
responders and HBe minus mutants HBV carriers nucleoside analogues like
lamivudine represents a new and clinically proven therapeutical option. However,
the longterm outcome and the problem of the emergence of HBV polymerase gene
mutants has not been completely understood.
PMID- 11014128
TI - ["Ultrasonographically detected liver lesion"--how to proceed?].
AB - Focal liver lesions found incidentally in ultrasound are predominantly
uncomplicated cysts, cavernous hemangiomas or typical metastases. In most of
these cases a reliable diagnosis can be made. Atypical findings, however, always
are suspicious being malignant. In this particular situation imaging methods,
such as CT, NMR or scintigraphy, should be applied. Despite of this a final
diagnosis may not be found in all cases. An ultrasound-guided fine-needle biopsy
is then required. Biopsy during laparotomy might be the procedure of choice in
some situations.
PMID- 11014129
TI - [Therapy of pancreatic and bile duct tumors: value of radiotherapy and
photodynamic therapy].
AB - Prognosis of pancreatic cancer and bile duct cancer is extraordinary poor.
Despite of the improvement in diagnostic procedures and the development of more
radical resectional procedures prolongation of survival could not have been
achieved yet. At the time of diagnosis only 20-30% of patients are suitable for
resection, thus the value of non resectional methods for palliation has to be
determined. Despite of numerous efforts to increase the local radiation dosage by
means of distinguished radiation techniques none of these procedures could
achieve an unequivocal prolongation of survival. After promising preliminary
results of intraoperative radiotherapy (IORT) in pancreatic cancer following
studies could not show a survival benefit for IORT allone or in combination with
extracorporal radiotherapy (EBRT). EBRT is indicated at best for local pain
control and is limited by the high radiation sensitivity of the adjacent organs.
Intracorporal radiotherapy or brachytherapy with iridium 129-labelled wires leeds
to local, intraluminal tumour control, but has also no influence on survival
time. Up to now, photodynamic therapy (PDT) of pancreatic cancer must be
characterized as highly experimental. But PDT can contribute to local tumour
control. Preliminary data of photodynamic therapy in bile duct cancer show good
results concerning reduction of cholestasis, improvement of life quality and even
prolongation of survival time. The value of these preliminary results is being
proved at present in controlled studies in comparison to mere endoprosthetic
supply at a few centers.
PMID- 11014130
TI - [Risk groups for pancreatic and bile duct carcinomas].
AB - Biliopancreatic carcinoma has a poor prognosis since the diagnosis of the tumor
occurs late when advanced disease is present. The identification of potential
causes and earlier diagnosis are needed to prevent the disease or identify it
early enough to improve survival. The main risk factors for pancreatic cancer
include advanced age, cigarette smoking, high-fat diet, diabetes mellitus,
chronic pancreatitis (especially hereditary pancreatitis) and a positive family
history of pancreatic cancer. The most important etiologic factor for the
development of gallbladder cancer is gallstone disease. Patients with anatomic
abnormalities and chronic inflammatory conditions (primary sclerosing
cholangitis, infections with parasites) have an increased incidence of bile duct
cancers. Several new and promising imaging techniques have recently become
available and our understanding of the mechanisms of carcinogenesis are growing
rapidly. However, there is currently no effective screening strategy applicable
and it is unknown when to begin screening. For pancreatic cancer, reduction of
risk is likely to occur with avoidance of smoking and promotion of healthful
diets. Cholecystectomy rates have increased since the introduction of new
laparoscopic techniques and will eventually reduce the incidence of gallbladder
cancer. Improved imaging techniques, the identification of new genes and a better
definition of genetic alterations that characterize preinvasive lesions will
hopefully allow to develop sensitive and specific technologies to screen and to
detect early biliopancreatic cancer for even premalignant lesions to improve the
mostly fatal prognosis if this tumor.
PMID- 11014132
TI - [Dengue fever in Denmark].
PMID- 11014131
TI - [Diabetic nephropathy. A modifiable risk factor].
PMID- 11014133
TI - [Risk factors in the progression of diabetic nephropathies].
AB - Diabetic nephropathy is a serious long-term complication of diabetes
characterized by persistent albuminuria (> 300 mg/24 h or 200 micrograms/min)
associated with a decline in GFR, increasing arterial blood pressure, and high
risk of cardiovascular morbidity and mortality. Diabetic nephropathy has become
the leading cause of end stage renal disease in Europe, USA and Japan. There is a
great inter-individual variation in the deterioration in GFR explained by genetic
and non-genetic progression promoters (risk factors for losing GFR). In
particular arterial blood pressure, glycaemic control, and albuminuria act as non
genetic promoters of progression. These factors are potentially modifiable.
Genetic promoters of progression have also been identified, mainly the
angiotensin converting enzyme insertion/deletion polymorphism. Knowledge of
progression promoters can identify patients with a poor prognosis and direct
therapy against modifiable risk factors, in particular hypertension and
hyperglycaemia.
PMID- 11014135
TI - [Hereditary dystonias].
AB - Dystonia is a heterogeneous, neurological disease characterized by involuntary,
sustained muscle contractions, frequently causing twisting and repetitive
movements or abnormal postures. The patients are often difficult to diagnose, and
the treatment is almost always only symptomatic. It is believed that about 75% of
all patients with dystonia have primary dystonia, and 25-85% of these are
hereditary. Seven gene loci for autosomal, dominant inherited dystonia and two
for X-linked, recessive inherited dystonia are known at present, but the
underlying genes are known only for DYT1 and DYT5. Testing is possible for these
two in Denmark. Growing molecular genetic knowledge will lead to earlier and
correct diagnosing, including prognosis, and may elucidate the pathogenesis,
making better treatment possible.
PMID- 11014134
TI - [Dengue fever and dengue hemorrhagic fever].
AB - Dengue virus is transmitted by mosquitoes and causes dengue fever/dengue
haemorrhagic fever throughout the tropical areas of the world. There is an
increasing incidence of dengue infections. Because of increasing travel activity,
infection among Danes travelling abroad as well as imported cases are expected to
be seen more frequently. In this review we describe the clinical manifestations,
diagnosis, pathogenesis, treatment and prevention of the disease.
PMID- 11014136
TI - [Bite wounds and infection prophylaxis. Evidence-based therapeutic
recommendations].
AB - Infections are common complications of bite wounds, changing in severity from
local cellulitis to life-threatening septicaemia. Treatment recommendations are
often contradictory and rarely reflect evidence-based medicine. Risk factors
associated with higher rates of infection include localization on the hands,
puncture wounds and age older than 50 years. The literature is critically
reviewed for evidence-based treatment of bite wounds. The results are discussed
with respect to common practice in Denmark.
PMID- 11014137
TI - [Dengue fever among 44 Danish travellers investigated in the department of
epidemics at the Rigshospitalet during 1988-1998].
AB - Dengue fever is a major cause of febrile illness in the tropics, and we describe
44 patients with dengue fever seen at Rigshospitalet, Copenhagen from 1988-98. A
worldwide increase in transmission of dengue fever was reflected in the number of
patients seen in 1997-1998. All patients had fever and headache, and were
biochemically characterised by thrombocytopenia, leucopenia, increased levels of
alanine aminotransferase and a rise in haematocrit. One patient had dengue
haemorrhagic fever, and two patients exhibited unusual reactions to the
infection, one in the form of extended febrile neutropenia complicated by an
episode of of E. coli septicaemia, and one patient developed progressive
paralysis of both legs, and remains partially paretic.
PMID- 11014138
TI - [The amount of time spent in processing of 40 cases involving involuntary
commitment under the legislation of 1989 in a Danish county 1990-1994].
AB - This investigation examines forty cases dealing with compulsory admission or
detention which have been presented at the Local Magistrates Court in a Danish
county under the Danish Mental Health Legislation of 1989 during a five year
period from 1990-1994. The amount of time spent in processing the cases by the
psychiatric department, the Forensic Medical Council and the magistrate was
registered. The results show a written psychiatric statement from the department
is available after seven to ten days. Five weeks pass when the case is presented
to the Forensic Medical Council, (four weeks with the Council and one week with
the magistrate). The importance of obtaining statements from the Forensic Medical
Council and the time spent in considering the cases with reference to the Justice
Department's survey of the Danish Mental Health Legislation of 1989 is discussed.
The investigation concludes that despite the resulting prolonged case evaluation
it is recommended that cases involving detainment are brought before the Forensic
Medical Council.
PMID- 11014140
TI - [Two years of experiences with a county clinic specialized for breast diseases].
PMID- 11014139
TI - [Stress and fertility. A follow-up study among couples planning the first
pregnancy].
AB - Mental distress has often been suggested as a cause of unexplained infertility.
However, the causal direction may well be from infertility to distress, and
prospective data are needed. We therefore followed 393 couples, who were planning
their first pregnancy, with prospective collection of information on distress
from termination of birth control until pregnancy for a maximum of six menstrual
cycles. The analyses included 1,475 menstrual cycles, and mental distress was
measured in each cycle by the General Health Questionnaire (GHQ). Urine samples
from each period of vaginal bleeding were analyzed for human chorionic
gonadotrophic hormone, indicating early embryonal loss. We found that for cycles
with the highest distress score (GHQ score above the 80 percentile) the
probability of conception per cycle was 12.8% compared to 16.5% in other cycles
(adjusted OR 0.6; 95% CI 0.4-1.0). The effect of distress was almost exclusively
found among women with long menstrual cycles (OR 0.1; 95% CI 0.01-0.4 and OR 0.9;
0.5-1.4 for women with cycles > or = 35 and < 35 days, respectively). An
increased incidence of early embryonal loss was also found among highly
distressed women with long cycles, but was based on a small number of
observations. It is concluded that psychological distress may be a risk factor
for reduced fertility in women with long menstrual cycles.
PMID- 11014141
TI - [Spontaneous infrapatellar tendon rupture in a patient with systemic lupus
erythematosus].
AB - A case is described of a 33-year old woman with systemic lupus erythematosus
(SLE) in longterm treatment with corticosteroids who experienced spontaneous
rupture of the left patellar tendon. A comparative study of 28 previously
reported cases of SLE patients with spontaneous tendon rupture in weight bearing
joints is performed. It is suggested that renal disease may be an etiological
factor for spontaneous tendon rupture in patients with systemic lupus
erythematosus.
PMID- 11014142
TI - [Dengue fever].
AB - Dengue virus infections have increased globally. This results in an increased
incidence of patients with dengue fever in Denmark. In order to draw attention to
this diagnosis among febrile persons returning from a stay in tropical and
subtropical areas, we present two cases of dengue virus infection and describe
the symptoms and diagnostic possibilities. Dengue Haemorrhagic Fever (DHF) is
supposed to occur only in persons who have previously had dengue virus infection
and who acquire a second infection with dengue virus.
PMID- 11014143
TI - [A complicated course of Salmonella gastroenteritis during antihypertensive
treatment].
AB - Although Salmonella gastroenteritis usually is a fairly mild and self-limiting
disease, serious complications are sometimes seen. We present a case that was
further complicated by treatment with enalapril. We recommend discontinuation of
treatment with ACE inhibitors in patients with any kind of ongoing
gastroenteritis with fluid loss in order to prevent a potentially serious
outcome.
PMID- 11014144
TI - [Breakthrough for gene therapy].
PMID- 11014145
TI - [Healthy soul].
PMID- 11014146
TI - [Screening for lung cancer--to prevent?].
PMID- 11014147
TI - [Helicobacter pylori diagnostics--how, when and by whom?].
PMID- 11014149
TI - Bridging the Taiwan Strait
PMID- 11014148
TI - [Genetic mapping].
PMID- 11014150
TI - Reviews for reviews' sake
PMID- 11014152
TI - UK advised to step up asteroid hunt
PMID- 11014151
TI - Doubts grow over discovery of fossilized 'dinosaur heart'.
PMID- 11014154
TI - Hunt for Higgs particle wins time for CERN collider
PMID- 11014153
TI - World Bank is urged to give greater priority to science
PMID- 11014155
TI - European space panel picks new priorities
PMID- 11014156
TI - NASA reaches out to universities.
PMID- 11014158
TI - Case of the stolen Enigma machine takes cryptic turn
PMID- 11014157
TI - Germline gene therapy needs tight control, says US panel.
PMID- 11014159
TI - Japan opens access to mouse cDNA data...and to report on strengths and weaknesses
of genomics centre.
PMID- 11014160
TI - A chemistry set for life.
PMID- 11014161
TI - Allowing gene patents could be an expensive mistake for the US.
PMID- 11014162
TI - No room on the carousel for meeting of like minds
PMID- 11014163
TI - Standardized addresses would make web easier.
PMID- 11014165
TI - Sky was not the limit for music-loving Herschel
PMID- 11014164
TI - The Durban Declaration is not accepted by all.
PMID- 11014166
TI - Good and bad science in US schools.
PMID- 11014168
TI - The Great Goodbye
PMID- 11014167
TI - Down to earth.
PMID- 11014169
TI - Electrochemistry. A moving oxygen story
PMID- 11014170
TI - Molecular biology. Small subunit, big science.
PMID- 11014171
TI - Galactic rotation in real time
PMID- 11014172
TI - Cancer. A radical approach to treatment.
PMID- 11014173
TI - Ocean biogeochemistry. Calcification and CO2.
PMID- 11014174
TI - AIDS. Escape from the immune system.
PMID- 11014175
TI - Developmental biology. Post-expressionist flies.
PMID- 11014176
TI - Elvin A. Kabat (1914-2000).
PMID- 11014177
TI - Membrane changes during hibernation.
PMID- 11014178
TI - Winter torpor in a large bird.
PMID- 11014179
TI - Cloning of mice to six generations.
PMID- 11014180
TI - Total silencing by intron-spliced hairpin RNAs.
PMID- 11014181
TI - Loosening of plant cell walls by expansins.
AB - Plant cell walls are the starting materials for many commercial products, from
lumber, paper and textiles to thickeners, films and explosives. The cell wall is
secreted by each cell in the plant body, forming a thin fibreglass-like network
with remarkable strength and flexibility. During growth, plant cells secrete a
protein called expansin, which unlocks the network of wall polysaccharides,
permitting turgor-driven cell enlargement. Germinating grass pollen also secretes
an unusual expansin that loosens maternal cell walls to aid penetration of the
stigma by the pollen tube. Expansin's action has puzzling implications for plant
cell-wall structure. The recent explosion of gene sequences and expression data
has given new hints of additional biological functions for expansins.
PMID- 11014182
TI - Structure of the 30S ribosomal subunit.
AB - Genetic information encoded in messenger RNA is translated into protein by the
ribosome, which is a large nucleoprotein complex comprising two subunits, denoted
30S and 50S in bacteria. Here we report the crystal structure of the 30S subunit
from Thermus thermophilus, refined to 3 A resolution. The final atomic model
rationalizes over four decades of biochemical data on the ribosome, and provides
a wealth of information about RNA and protein structure, protein-RNA interactions
and ribosome assembly. It is also a structural basis for analysis of the
functions of the 30S subunit, such as decoding, and for understanding the action
of antibiotics. The structure will facilitate the interpretation in molecular
terms of lower resolution structural data on several functional states of the
ribosome from electron microscopy and crystallography.
PMID- 11014183
TI - Functional insights from the structure of the 30S ribosomal subunit and its
interactions with antibiotics.
AB - The 30S ribosomal subunit has two primary functions in protein synthesis. It
discriminates against aminoacyl transfer RNAs that do not match the codon of
messenger RNA, thereby ensuring accuracy in translation of the genetic message in
a process called decoding. Also, it works with the 50S subunit to move the tRNAs
and associated mRNA by precisely one codon, in a process called translocation.
Here we describe the functional implications of the high-resolution 30S crystal
structure presented in the accompanying paper, and infer details of the
interactions between the 30S subunit and its tRNA and mRNA ligands. We also
describe the crystal structure of the 30S subunit complexed with the antibiotics
paromomycin, streptomycin and spectinomycin, which interfere with decoding and
translocation. This work reveals the structural basis for the action of these
antibiotics, and leads to a model for the role of the universally conserved 16S
RNA residues A1492 and A1493 in the decoding process.
PMID- 11014184
TI - The accelerations of stars orbiting the Milky Way's central black hole
AB - Recent measurements of the velocities of stars near the centre of the Milky Way
have provided the strongest evidence for the presence of a supermassive black
hole in a galaxy, but the observational uncertainties poorly constrain many of
the black hole's properties. Determining the accelerations of stars in their
orbits around the centre provides much more precise information about the
position and mass of the black hole. Here we report measurements of the
accelerations of three stars located approximately 0.005 pc (projected on the
sky) from the central radio source Sagittarius A* (Sgr A*); these accelerations
are comparable to those experienced by the Earth as it orbits the Sun. These data
increase the inferred minimum mass density in the central region of the Galaxy by
an order of magnitude relative to previous results, and localize the dark mass to
within 0.05 +/- 0.04 arcsec of the nominal position of Sgr A*. In addition, the
orbital period of one of the observed stars could be as short as 15 years,
allowing us the opportunity in the near future to observe an entire period.
PMID- 11014185
TI - Onset of antiferromagnetism in heavy-fermion metals
AB - There are two main theoretical descriptions of antiferromagnets. The first arises
from atomic physics, which predicts that atoms with unpaired electrons develop
magnetic moments. In a solid, the coupling between moments on nearby ions then
yields antiferromagnetic order at low temperatures. The second description, based
on the physics of electron fluids or 'Fermi liquids' states that Coulomb
interactions can drive the fluid to adopt a more stable configuration by
developing a spin density wave. It is at present unknown which view is
appropriate at a 'quantum critical point' where the antiferromagnetic transition
temperature vanishes. Here we report neutron scattering and bulk magnetometry
measurements of the metal CeCu(6-x)Au(x), which allow us to discriminate between
the two models. We find evidence for an atomically local contribution to the
magnetic correlations which develops at the critical gold concentration (x(c) =
0.1), corresponding to a magnetic ordering temperature of zero. This contribution
implies that a Fermi-liquid-destroying spin-localizing transition, unanticipated
from the spin density wave description, coincides with the antiferromagnetic
quantum critical point.
PMID- 11014186
TI - Detection of geometric phases in superconducting nanocircuits
AB - When a quantum-mechanical system undergoes an adiabatic cyclic evolution, it
acquires a geometrical phase factor' in addition to the dynamical one; this
effect has been demonstrated in a variety of microscopic systems. Advances in
nanotechnology should enable the laws of quantum dynamics to be tested at the
macroscopic level, by providing controllable artificial two-level systems (for
example, in quantum dots and superconducting devices). Here we propose an
experimental method to detect geometric phases in a superconducting device. The
setup is a Josephson junction nanocircuit consisting of a superconducting
electron box. We discuss how interferometry based on geometrical phases may be
realized, and show how the effect may be applied to the design of gates for
quantum computation.
PMID- 11014187
TI - Ordering and self-organization in nanocrystalline silicon
AB - The spontaneous formation of organized nanocrystals in semiconductors has been
observed during heteroepitaxial growth and chemical synthesis. The ability to
fabricate size-controlled silicon nanocrystals encapsulated by insulating SiO2
would be of significant interest to the microelectronics industry. But
reproducible manufacture of such crystals is hampered by the amorphous nature of
SiO2 and the differing thermal expansion coefficients of the two materials.
Previous attempts to fabricate Si nanocrystals failed to achieve control over
their shape and crystallographic orientation, the latter property being important
in systems such as Si quantum dots. Here we report the self-organization of Si
nanocrystals larger than 80 A into brick-shaped crystallites oriented along the
(111) crystallographic direction. The nanocrystals are formed by the solid-phase
crystallization of nanometre-thick layers of amorphous Si confined between SiO2
layers. The shape and orientation of the crystallites results in relatively
narrow photoluminescence, whereas isotropic particles produce qualitatively
different, broad light emission. Our results should aid the development of
maskless, reproducible Si nanofabrication techniques.
PMID- 11014188
TI - Direct electrochemical reduction of titanium dioxide to titanium in molten
calcium chloride
AB - Many reactive metals are difficult to prepare in pure form without complicated
and expensive procedures. Although titanium has many desirable properties (it is
light, strong and corrosion-resistant), its use has been restricted because of
its high processing cost. In the current pyrometallurgical process--the Kroll
process--the titanium minerals rutile and ilmenite are carbochlorinated to remove
oxygen, iron and other impurities, producing a TiCl4 vapour. This is then reduced
to titanium metal by magnesium metal; the by-product MgCl2 is removed by vacuum
distillation. The prediction that this process would be replaced by an
electrochemical route has not been fulfilled; attempts involving the electro
deposition of titanium from ionic solutions have been hampered by difficulties in
eliminating the redox cycling of multivalent titanium ions and in handling very
reactive dendritic products. Here we report an electrochemical method for the
direct reduction of solid TiO2, in which the oxygen is ionized, dissolved in a
molten salt and discharged at the anode, leaving pure titanium at the cathode.
The simplicity and rapidity of this process compared to conventional routes
should result in reduced production costs and the approach should be applicable
to a wide range of metal oxides.
PMID- 11014189
TI - Reduced calcification of marine plankton in response to increased atmospheric
CO2.
AB - The formation of calcareous skeletons by marine planktonic organisms and their
subsequent sinking to depth generates a continuous rain of calcium carbonate to
the deep ocean and underlying sediments. This is important in regulating marine
carbon cycling and ocean-atmosphere CO2 exchange. The present rise in atmospheric
CO2 levels causes significant changes in surface ocean pH and carbonate
chemistry. Such changes have been shown to slow down calcification in corals and
coralline macroalgae, but the majority of marine calcification occurs in
planktonic organisms. Here we report reduced calcite production at increased CO2
concentrations in monospecific cultures of two dominant marine calcifying
phytoplankton species, the coccolithophorids Emiliania huxleyi and Gephyrocapsa
oceanica. This was accompanied by an increased proportion of malformed coccoliths
and incomplete coccospheres. Diminished calcification led to a reduction in the
ratio of calcite precipitation to organic matter production. Similar results were
obtained in incubations of natural plankton assemblages from the north Pacific
ocean when exposed to experimentally elevated CO2 levels. We suggest that the
progressive increase in atmospheric CO2 concentrations may therefore slow down
the production of calcium carbonate in the surface ocean. As the process of
calcification releases CO2 to the atmosphere, the response observed here could
potentially act as a negative feedback on atmospheric CO2 levels.
PMID- 11014190
TI - Increased dissolved oxygen in Pacific intermediate waters due to lower rates of
carbon oxidation in sediments.
AB - Concentrations of dissolved oxygen in the ocean seem to correlate well with
climate instabilities over the past 100,000 years. For example, the concentration
of dissolved oxygen in Pacific intermediate waters was considerably higher during
Pleistocene glacial periods than it is today. This has been inferred from the
presence of bioturbated sediments, implying that oxygen levels were sufficient
for burrowing organisms to live. Today, basins in the northeastern Pacific Ocean
are floored by laminated sediments implying lower oxygen levels, which may be
explained by reduced ventilation. Here we report a recent return to bioturbated
sediments in the northeastern Pacific Ocean since the late 1970s. From the carbon
isotope composition of benthic foraminifers living in the sediment, we infer a
twofold decrease in the carbon oxidation rate occurring within sediments,
equivalent to an increase in dissolved oxygen concentration of 15-20 micromoles
per litre. These changes, at the edges of the Santa Barbara, Santa Monica and
Alfonso basins, are coincident with a change in North Pacific climate which has
reduced upwelling by 20-30% and increased sea surface temperatures by 1.5-3
degrees C. This suggests that climate effects on surface productivity, reducing
the supply organic matter to sediments, may have had a greater effect on benthic
oxygen levels than changes in ocean circulation patterns.
PMID- 11014191
TI - Variance in ecological consumer-resource interactions.
AB - Food-web models use the effect size of trophic interactions to predict consumer
resource dynamics. These models anticipate that strong effects of consumers
increase spatial and temporal variability in abundance of species, whereas weak
effects dampen fluctuations. Empirical evidence indicates that opposite patterns
may occur in natural assemblages. Here I show that spatial variance in the
distribution of resource populations is sensitive to changes in the variance of
the trophic interaction, in addition to the mean effect of consumers, relative to
other causes of spatial variability. Simulations indicate that both strong and
weak direct effects of consumers can promote spatial variability in abundance of
resources, but only trophic interactions with a large mean effect size can reduce
variation. Predictions of the model agree with the results of repeated field
experiments and are consistent with data from published consumer-resource
interactions, proving to be robust across widely varying environmental conditions
and species' life histories. Thus, food-web models that embody variance in
trophic interactions may have increased capacity to explain the wide range of
effects of consumers documented in empirical studies.
PMID- 11014192
TI - Body image as a visuomotor transformation device revealed in adaptation to
reversed vision.
AB - People adapt with remarkable flexibility to reversal of the visual field caused
by prism spectacles. With sufficient time, this adaptation restores visually
guided behaviour and perceptual harmony between the visible and tactile worlds.
Although it has been suggested that seeing one's own body is crucial for
adaptation, the underlying mechanisms are unclear. Here we show that a new
representation of visuomotor mapping with respect to the hands emerges in a month
during adaptation to reversed vision. The subjects become bi-perceptual, or able
to use both new and old representations. In a visual task designed to assess the
new hand representation, subjects identified visually presented hands as left or
right by matching the picture to the representation of their own hands.
Functional magnetic resonance imaging showed brain activity in the left posterior
frontal cortex (Broca's area) that was unique to the new hand representations of
both hands, together with activation in the intraparietal sulcus and prefrontal
cortex. The emergence of the new hand representation coincided with the
adaptation of perceived location of visible objects in space. These results
suggest that the hand representation operates as a visuomotor transformation
device that provides an arm-centred frame of reference for space perception.
PMID- 11014193
TI - IRS-2 pathways integrate female reproduction and energy homeostasis.
AB - Severe dietary restriction, catabolic states and even short-term caloric
deprivation impair fertility in mammals. Likewise, obesity is associated with
infertile conditions such as polycystic ovary syndrome. The reproductive status
of lower organisms such as Caenorhabditis elegans is also modulated by
availability of nutrients. Thus, fertility requires the integration of
reproductive and metabolic signals. Here we show that deletion of insulin
receptor substrate-2 (IRS-2), a component of the insulin/insulin-like growth
factor-1 signalling cascade, causes female infertility. Mice lacking IRS-2 have
small, anovulatory ovaries with reduced numbers of follicles. Plasma
concentrations of luteinizing hormone, prolactin and sex steroids are low in
these animals. Pituitaries are decreased in size and contain reduced numbers of
gonadotrophs. Females lacking IRS-2 have increased food intake and obesity,
despite elevated levels of leptin. Our findings indicate that insulin, together
with leptin and other neuropeptides, may modulate hypothalamic control of
appetite and reproductive endocrinology. Coupled with findings on the role of
insulin-signalling pathways in the regulation of fertility, metabolism and
longevity in C. elegans and Drosophila, we have identified an evolutionarily
conserved mechanism in mammals that regulates both reproduction and energy
homeostasis.
PMID- 11014194
TI - Cell-fate conversion of lymphoid-committed progenitors by instructive actions of
cytokines.
AB - The primary role of cytokines in haemato-lymphopoiesis is thought to be the
regulation of cell growth and survival. But the instructive action of cytokines
in haematopoiesis has not been well addressed. Here we show that a clonogenic
common lymphoid progenitor, a bone marrow-resident cell that gives rise
exclusively to lymphocytes (T, B and natural killer cells), can be redirected to
the myeloid lineage by stimulation through exogenously expressed interleukin (IL)
2 and GM-CSF (granulocyte/macrophage colony-stimulating factor) receptors.
Analysis of mutants of the beta-chain of the IL-2 receptor revealed that the
granulocyte- and monocyte-differentiation signals are triggered by different
cytoplasmic domains, showing that the signalling pathway(s) responsible for these
unique developmental outcomes are separable. Finally, we show that the endogenous
myelomonocytic cytokine receptors for GM-CSF and macrophage colony-stimulating
factor (M-CSF) are expressed at low to moderate levels on the more primitive
haematopoietic stem cells, are absent on common lymphoid progenitors, and are
upregulated after myeloid lineage induction by IL-2. We conclude that cytokine
signalling can regulate cell-fate decisions and propose that a critical step in
lymphoid commitment is downregulation of cytokine receptors that drive myeloid
cell development.
PMID- 11014195
TI - Tat-specific cytotoxic T lymphocytes select for SIV escape variants during
resolution of primary viraemia.
AB - Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV)
infections are characterized by early peaks of viraemia that decline as strong
cellular immune responses develop. Although it has been shown that virus-specific
CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV
and SIV infection, the data have been controversial. Here we show that Tat
specific CD8-positive T-lymphocyte responses select for new viral escape variants
during the acute phase of infection. We sequenced the entire virus immediately
after the acute phase, and found that amino-acid replacements accumulated
primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be
significantly involved in controlling wild-type virus replication, and suggests
that responses against viral proteins that are expressed early during the viral
life cycle might be attractive targets for HIV vaccine development.
PMID- 11014196
TI - Superoxide dismutase as a target for the selective killing of cancer cells.
AB - Superoxide dismutases (SOD) are essential enzymes that eliminate superoxide
radical (O2-) and thus protect cells from damage induced by free radicals. The
active O2- production and low SOD activity in cancer cells may render the
malignant cells highly dependent on SOD for survival and sensitive to inhibition
of SOD. Here we report that certain oestrogen derivatives selectively kill human
leukaemia cells but not normal lymphocytes. Using complementary DNA microarray
and biochemical approaches, we identify SOD as a target of this drug action and
show that chemical modifications at the 2-carbon (2-OH, 2-OCH3) of the
derivatives are essential for SOD inhibition and for apoptosis induction.
Inhibition of SOD causes accumulation of cellular O2- and leads to free-radical
mediated damage to mitochondrial membranes, the release of cytochrome c from
mitochondria and apoptosis of the cancer cells. Our results indicate that
targeting SOD may be a promising approach to the selective killing of cancer
cells, and that mechanism-based combinations of SOD inhibitors with free-radical
producing agents may have clinical applications.
PMID- 11014197
TI - A chemical switch for inhibitor-sensitive alleles of any protein kinase.
AB - Protein kinases have proved to be largely resistant to the design of highly
specific inhibitors, even with the aid of combinatorial chemistry. The lack of
these reagents has complicated efforts to assign specific signalling roles to
individual kinases. Here we describe a chemical genetic strategy for sensitizing
protein kinases to cell-permeable molecules that do not inhibit wild-type
kinases. From two inhibitor scaffolds, we have identified potent and selective
inhibitors for sensitized kinases from five distinct subfamilies. Tyrosine and
serine/threonine kinases are equally amenable to this approach. We have analysed
a budding yeast strain carrying an inhibitor-sensitive form of the cyclin
dependent kinase Cdc28 (CDK1) in place of the wild-type protein. Specific
inhibition of Cdc28 in vivo caused a pre-mitotic cell-cycle arrest that is
distinct from the G1 arrest typically observed in temperature-sensitive cdc28
mutants. The mutation that confers inhibitor-sensitivity is easily identifiable
from primary sequence alignments. Thus, this approach can be used to
systematically generate conditional alleles of protein kinases, allowing for
rapid functional characterization of members of this important gene family.
PMID- 11014198
TI - The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans.
AB - In metazoans, most pre-messenger RNAs contain introns that are removed by
splicing. The spliced mRNAs are then exported to the cytoplasm. Recent studies
showed that splicing promotes efficient mRNA export, but the mechanism for
coupling these two processes is not known. Here we show that Aly, the metazoan
homologue of the yeast mRNA export factor Yralp (ref. 2), is recruited to
messenger ribonucleoprotein (mRNP) complexes generated by splicing. In contrast,
Aly does not associate with mRNPs assembled on identical mRNAs that already have
no introns or with heterogenous nuclear RNP (hnRNP) complexes. Aly is recruited
during spliceosome assembly, and then becomes tightly associated with the spliced
mRNP. Aly shuttles between the nucleus and cytoplasm, and excess recombinant Aly
increases both the rate and efficiency of mRNA export in vivo. Consistent with
its splicing-dependent recruitment, Aly co-localizes with splicing factors in the
nucleus. We conclude that splicing is required for efficient mRNA export as a
result of coupling between the splicing and the mRNA export machineries.
PMID- 11014199
TI - Chromodomains are protein-RNA interaction modules.
AB - In Drosophila, compensation for the reduced dosage of genes located on the single
male X chromosome involves doubling their expression in relation to their
counterparts on female X chromosomes. Dosage compensation is an epigenetic
process involving the specific acetylation of histone H4 at lysine 16 by the
histone acetyltransferase MOF. Although MOF is expressed in both sexes, it only
associates with the X chromosome in males. Its absence causes male-specific
lethality. MOF is part of a chromosome-associated complex comprising male
specific lethal (MSL) proteins and at least one non-coding roX RNA. How MOF is
integrated into the dosage compensation complex is unknown. Here we show that
association of MOF with the male X chromosome depends on its interaction with
RNA. MOF specifically binds through its chromodomain to roX2 RNA in vivo. In
vitro analyses of the MOF and MSL-3 chromodomains indicate that these
chromodomains may function as RNA interaction modules. Their interaction with non
coding RNA may target regulators to specific chromosomal sites.
PMID- 11014200
TI - Image reconstructions of helical assemblies of the HIV-1 CA protein.
AB - The type 1 human immunodeficiency virus (HIV-1) contains a conical capsid
comprising approximately 1,500 CA protein subunits, which organizes the viral RNA
genome for uncoating and replication in a new host cell. In vitro, CA
spontaneously assembles into helical tubes and cones that resemble authentic
viral capsids. Here we describe electron cryo-microscopy and image
reconstructions of CA tubes from six different helical families. In spite of
their polymorphism, all tubes are composed of hexameric rings of CA arranged with
approximate local p6 lattice symmetry. Crystal structures of the two CA domains
were 'docked' into the reconstructed density, which showed that the amino
terminal domains form the hexameric rings and the carboxy-terminal dimerization
domains connect each ring to six neighbours. We propose a molecular model for the
HIV-1 capsid that follows the principles of a fullerene cone, in which the body
of the cone is composed of curved hexagonal arrays of CA rings and the ends are
closed by inclusion of 12 pentagonal 'defects'.
PMID- 11014201
TI - Taiwan backs experience in quest for biotech success.
PMID- 11014202
TI - Unfavourable economics put postdocs across Europe under strain.
PMID- 11014203
TI - Postdocs reject academic research.
PMID- 11014204
TI - The power of two--molecular differentiation of the vascular and bone actions of
the natriuretic peptides.
PMID- 11014205
TI - Hepatic growth hormone signaling in the late gestation fetal rat.
AB - The role of GH in the developing fetus is poorly understood. Several studies have
demonstrated a limited role for GH in late fetal life. In fact, few data are
available regarding GH signal transduction in the late gestation fetus. We
therefore focused on a comparison of hepatic GH signaling in near-term fetal rats
[embryonic day 19 (E19)] and adult rats using a combination of in vitro studies
employing hepatocytes in primary culture and in vivo studies. We found that GH
receptor (GHr) binding was comparable in fetal liver and adult liver. The long
isoform of the GHr underwent tyrosine phosphorylation in response to GH
stimulation of E19 fetal hepatocytes in a manner similar to that seen in cultured
adult hepatocytes. Furthermore, downstream signaling via the Janus kinase-2
tyrosine kinase, STAT1 (signal transducer and activator of transcription), and
STAT5 was also intact in both, as demonstrated by the tyrosine phosphorylation of
these signaling proteins. To confirm the relevance of these findings to the in
vivo situation, GH was directly administered by ip injection to E 19 fetal and
adult rats. In both cases, tyrosine phosphorylation of STAT5 was markedly and
rapidly induced. Finally, transfection of E19 fetal hepatocytes with GH
responsive reporter elements [Spi2.1(-275/+85)-CAT and 8xGHRE-TKCAT] demonstrated
intact transcriptional regulation. Our data indicate that GHr abundance and
activity as well as downstream GH signaling are similar in the late gestation
fetal rat and in the adult and that these mechanisms appear capable of supporting
physiological GH functions in the developing liver.
PMID- 11014206
TI - Conformational changes and coactivator recruitment by novel ligands for estrogen
receptor-alpha and estrogen receptor-beta: correlations with biological character
and distinct differences among SRC coactivator family members.
AB - Ligands for the estrogen receptor (ER) that have the capacity to selectively bind
to or activate the ER subtypes ERalpha or ERbeta would be useful in elucidating
the biology of these two receptors and might assist in the development of
estrogen pharmaceuticals with improved tissue selectivity. In this study, we
examine three compounds of novel structure that act as ER subtype-selective
ligands. These are a propyl pyrazole triol (PPT), which is a potent agonist on
ERalpha but is inactive on ERbeta, and a pair of substituted tetrahydrochrysenes
(THC), one enantiomer of which (S,S-THC) is an agonist on both ERalpha and
ERbeta, the other (R,R-THC) being an agonist on ERalpha but an antagonist on
ERbeta. To investigate the molecular mechanisms underlying the ER subtype
selective actions of these compounds, we have determined the conformational
changes induced in ERalpha and ERbeta by these ligands using protease digestion
sensitivity, and we have tested the ability of these ligands to promote the
recruitment of representatives of the three SRC/p160 coactivator protein family
members (SRC-1, GRIP-1, ACTR, respectively) to ERalpha and ERbeta using yeast two
hybrid and glutathione-S-transferase (GST) pull-down assays. We find that the
ligand-ER protease digestion pattern is distinctly different for stimulatory and
inhibitory ligands, and that this assay, as well as coactivator recruitment, are
excellent indicators of their agonist/antagonist character. Interestingly
however, compared with estradiol, the novel agonist ligands show some
quantitative differences in their ability to recruit SRC-1, -2, and -3. This
implies that while generally similar to estradiol, these ligands induce ER
conformations that differ somewhat from that induced by estradiol, differences
that are illustrative of the nature of their biological character. The
application of methods to characterize the conformations induced in ER subtypes
by novel ligands, as done in this study, enables a greater understanding of how
ligand-receptor conformations relate to estrogen agonist or antagonist behavior.
PMID- 11014207
TI - Double-stranded ribonucleic acid decreases C6 rat glioma cell numbers: effects on
insulin-like growth factor I gene expression and action.
AB - Poly(IC), a synthetic double-stranded RNA copolymer of inosinic and cytidilic
acids, decreases the growth of normal and tumorigenic cells. We tested the
hypothesis that Poly(IC) decreases C6 glioma cell growth by disrupting an
autocrine insulin-like growth factor I (IGF-I) growth loop. Addition of Poly(IC)
decreased C6 cell number in confluent and sparse cultures in a dose-dependent
manner. Addition of exogenous IGF-I partially compensated for the decrease in
cell number caused by Poly(IC) in confluent and subconfluent cultures of C6
cells, suggesting that one mechanism of Poly(IC) action is through down
regulation of IGF-I gene expression and/or action. Treatment of confluent C6
cells with 10 and 200 microg/ml Poly(IC) for 24 h decreased IGF-I messenger RNA
(mRNA) levels to 50% and 25% of the control value, respectively. Treatment of C6
cells with 200 microg/ml Poly(IC) for 24 h reduced IGF-I receptor mRNA levels to
50% of the control level. IGF-binding protein-1 (IGFBP-1), -2, and -6 mRNAs were
not expressed in the C6 cells used in this study. Treatment of C6 cells with 200
microg/ml Poly(IC) for 24 h reduced IGFBP-4 mRNA and IGFBP-5 mRNA levels to 26%
and 29% of the control level, respectively. There was no significant change in
IGFBP-3, insulin receptor, or actin mRNA levels with Poly(IC) treatment.
Treatment of confluent C6 cells with 200 microg/ml Poly(IC) for 24 h decreased
levels of immunoreactive IGF-I in conditioned medium (CM) to 55% of the control
value, decreased IGF-I receptor beta-subunit levels to 28% of the control value,
and decreased levels of IGFBP-3, IGFBP-4, and IGFBP-5 protein in CM to 45%, 50%,
and 30% of the control values, respectively. There was no significant change in
actin and tubulin protein levels with Poly(IC) treatment. These results suggest
that IGF-I gene expression is down-regulated by Poly(IC) treatment and that IGF-I
bioavailability and action in C6 cells are also altered due to decreases in IGF-I
receptor and binding protein levels.
PMID- 11014208
TI - Modulation of pituitary somatostatin receptor subtype (sst1-5) messenger
ribonucleic acid levels by changes in the growth hormone axis.
AB - The role of individual components of the hypothalamic-pituitary-GH axis in the
modulation of pituitary somatostatin (SRIF) receptor subtype (sst1-5) synthesis
was assessed using multiplex RT-PCR to measure receptor messenger RNA (mRNA)
levels in normal rats and spontaneous dwarf rats (SDRs). In SDRs, a strain with
no immunodetectable GH, pituitary sst1 and sst2 mRNA levels were elevated, sst5
mRNA levels were reduced, and sst3 and sst4 mRNA levels did not significantly
differ from those in normal controls. Treatment of SDRs with GH (72 h), but not
insulin-like growth factor I, significantly decreased sst2 mRNA levels and
increased sst4 and sst5 mRNA levels above vehicle-treated control levels. To test
whether more rapid changes in circulating GH levels could alter SRIF receptor
subtype expression, normal rats were infused (iv) with GH-releasing hormone
(GHRH) for 4 h in the presence or absence of SRIF antiserum. GHRH infusion
increased pituitary sst1 and sst2 and decreased sst5, but had no effect on sst3
and sst4 mRNA levels. Immunoneutralization of SRIF, which produced a rise in
circulating GH levels, did not alter basal or GHRH-mediated SRIF receptor subtype
expression. These observations indicate that acute suppression of SRIF tone does
not regulate pituitary SRIF receptor subtype mRNA levels in vivo. The possibility
that elevated circulating GH concentrations induced by GHRH infusion were
responsible for the observed changes in SRIF receptor subtype mRNA levels was
examined by infusing SDRs with GHRH for 4 h. GHRH did not increase sst1 mRNA
levels in SDRs above their already elevated value. However, GHRH infusion
produced an increase in sst2 and a decrease in sst5 mRNA levels similar to those
observed in normal rats, indicating that the acute effects of GHRH on SRIF
receptor subtype expression are independent of circulating GH levels. Primary rat
pituitary cell cultures were incubated with GHRH (10 nM) or forskolin (10 microM)
for 4 h to determine whether GHRH could directly mediate SRIF receptor subtype
mRNA. GHRH treatment increased sst1 and sst2 mRNA levels and decreased sst5 mRNA
levels, but had no effect on sst3 and sst4, similar to the results in vivo. The
effect of forskolin mimicked that of GHRH on sst1, sst2, and sst5 mRNA,
suggesting that GHRH acts through cAMP to directly mediate gene transcription or
mRNA stability of these SRIF receptor subtypes. In addition, forskolin reduced
sst3 and sst4 expression. These results strongly suggest that rat pituitary sst1,
sst2, and sst5 mRNA levels are regulated both in vivo and in vitro by GHRH. The
stimulatory action of GHRH on sst1 and sst2 and the inhibitory action on sst5
indicate that these receptor subtypes have independent and unique roles in the
modulation of pituitary GH release.
PMID- 11014209
TI - Prolactin (PRL) receptor gene expression in mouse adipose tissue: increases
during lactation and in PRL-transgenic mice.
AB - There are indications that PRL may exert important metabolic actions on adipose
tissue in different species. However, with the exception of birds, the receptor
has not been identified in white adipose tissue. The present study was designed
to examine the possible expression and regulation of the PRL receptor (PRLR) in
mouse adipose tissue. The long PRLR messenger RNA (mRNA) splice form (L-PRLR) and
two short splice forms (S2- and S3-PRLR) were detected in mouse adipose tissue by
RT-PCR. Furthermore, L-PRLR mRNA was detected by ribonuclease protection assay.
Immunoreactive PRLR with a relative molecular mass of 95,000 was revealed by
immunoblotting. Furthermore, L-PRLR mRNA expression was demonstrated in primary
isolated adipocytes. In mouse adipose tissue, the level of L-PRLR mRNA expression
increased 2.3-fold during lactation compared with those in virgin and pregnant
mice. In contrast, in the liver the expression of L-PRLR increased 3.4-fold
during pregnancy compared with those in virgin and lactating mice. When comparing
the levels of L-PRLR expression in virgin female and male mice, no difference was
detected in adipose tissue. However, in virgin female liver the expression was
4.5-fold higher than that in male liver. As PRL up-regulates its own receptor in
some tissues, we analyzed L-PRLR expression in PRL-transgenic female and male
mice. In PRL-transgenic mice L-PRLR expression was significantly increased in
both adipose tissue (1.4-fold in females and 2.4-fold in males) and liver (1.9
fold in females and 2.7-fold in males) compared with that in control mice.
Furthermore, in female PRL-transgenic mice retroperitoneal adipose tissue was
decreased in weight compared with that in control mice. However, no difference
was detected when comparing the masses of parametrial adipose tissue. Our results
suggest a direct role for PRL, mediated by PRLR, in modulating physiological
events in adipose tissue.
PMID- 11014210
TI - Evidence that cleavage of the thyrotropin receptor involves a "molecular ruler"
mechanism: deletion of amino acid residues 305-320 causes a spatial shift in
cleavage site 1 independent of amino acid motif.
AB - Some TSH receptors (TSHR) on the cell surface cleave into A and B subunits.
Cleavage at upstream Site 1 is followed by the proteolytic excision of an
intervening C peptide region terminating at a downstream Site 2. Although present
evidence suggests that Site 1 lies between amino acid residues 303 and 317, the
mechanism and exact amino acid(s) involved in cleavage are unknown. Previous
amino acid substitutions at Site 1 failed to abrogate cleavage. We, therefore,
performed deletion mutations within this region. Cleavage of cell surface TSHR,
detected by 125I-TSH cross-linking to intact cells, was not prevented by deletion
of four individual segments within the Site 1 cleavage region (delta305-308,
delta309-312, delta313-316, delta317-320). However, deletion of the entire region
(delta305-320) reduced the extent of cleavage and shifted the cleavage site
upstream of the glycan at amino acid residue N302. Elimination of this glycan
(N302Q substitution) reversed the effect of deleting amino acid residues 305-320
on TSHR cleavage, suggesting that reduced cleavage at the new, upstream cleavage
site was caused by steric hindrance by the glycan at N302. In summary, deletion,
as opposed to mutagenesis, of the TSHR cleavage Site 1 region produces a spatial
shift in TSHR cleavage Site 1 from downstream to upstream of the glycan at N302.
These observations provide strong evidence that TSHR cleavage at this site does
not occur at a particular amino acid motif and suggests that cleavage involves a
"molecular ruler" mechanism involving cleavage at a fixed distance from a
protease attachment site.
PMID- 11014211
TI - Proliferation of mouse mammary epithelial cells in vitro: interactions among
epidermal growth factor, insulin-like growth factor I, ovarian hormones, and
extracellular matrix proteins.
AB - The purpose of the present study was to investigate the role of extracellular
matrix proteins (ECMs; collagens I and IV, fibronectin, and laminin) in
modulating proliferative responses of normal mammary epithelial cells in serum
free culture to epidermal growth factor (EGF) and insulin-like growth factor I
(IGF-I). As EGF and IGF-I can alter steroid responses, the interactions among
growth factors, estrogen, and R5020 were also investigated. We report the novel
finding that all ECMs tested, but not a nonspecific attachment factor, poly-L
lysine (PL), promoted a highly synergistic proliferative response to EGF plus IGF
I. EGF receptors were significantly increased with culture time on all ECMs, but
not on PL. IGF receptor expression was significantly 2- to 4-fold higher on all
ECMs compared with PL. EGF decreased IGF-binding protein-2 (IGFBP-2) and IGFBP-3
by more than 50% in the presence of IGF-I on PL or collagen I. These results
indicate that ECM-specific IGF-I/EGF synergism occurs in response to ECM up
regulation of growth factor receptors and EGF down-regulation of inhibitory
IGFBPs. Growth factors did not synergize with estrogen and/or R5020. Instead,
estrogen plus R5020 decreased EGF-plus IGF-I-induced proliferation in an ECM
dependent manner. These studies demonstrate that proliferation of normal mammary
epithelial cells involves complex interactions among steroids, growth factors,
binding proteins, and ECMs.
PMID- 11014212
TI - Transcriptional regulation of human 11beta-hydroxylase (hCYP11B1).
AB - Steroid 11beta-hydroxylase is a mitochondrial enzyme that catalyzes the
conversion of deoxycortisol to cortisol. The gene encoding human 11beta
hydroxylase (hCYP11B1) is expressed in the adrenal cortex under the control of
circulating levels of ACTH. The current study was undertaken to define the cis
regulatory elements and transacting factors that regulate hCYP11B1 transcription.
The hCYP11B1 5'-flanking DNA was studied using transient transfection of
luciferase reporter constructs in NCI-H295R human adrenocortical cells. A cAMP
analogue ((Bu)2cAMP) increased expression of a construct containing -1102 bp of
hCYP11B1 5'-flanking DNA (pB1-1102). An element at position -71/-64 (TGACGTGA,
previously termed Ad1) resembling a consensus cAMP response element (CRE) was
required for maximal induction by cAMP. The Ad1 element bound several
transcriptional factors in electrophoretic mobility shift assays, including CRE
binding protein, activating transcription factor-1 (ATF-1), and ATF-2, but only
the ATF-2 complex migrated similarly to a complex seen using H295R nuclear
extract. In addition, Western analysis of H295R and adrenal lysates demonstrated
expression of high levels of ATF-2 and ATF-1. CRE-binding protein levels varied
among the strains of H295R cells tested. Transcription of CYP11B1 also appeared
to be regulated by steroidogenic factor-1 (SF-1). Luciferase reporter gene
activity was increased after cotransfection with expression vectors containing SF
1. An element in hCYP11B1 at positions 242/-234 (CCAAGGCTC), previously termed
Ad4, was required for maximal induction by SF-1 and was found to bind SF-1 in
electrophoretic mobility shift assays. The key role for SF-1 in hCYP11B1
transcription is in contrast to its lack of an effect on expression of the
hCYP11B2 (aldosterone synthase) isozyme. The differential effects of SF-1 on
transcription of hCYP11B1 and hCYP11B2 may be one of the mechanisms controlling
differential expression of these isozymes within the zonae fasciculata and
glomerulosa of the human adrenal cortex.
PMID- 11014213
TI - Effects of arsenite on estrogen receptor-alpha expression and activity in MCF-7
breast cancer cells.
AB - To determine whether arsenite has estrogen-like activities, the effects of this
compound on estrogen receptor-alpha (ERalpha) and other estrogen-regulated genes
were measured in the human breast cancer cell line MCF-7. Treatment of cells with
1 microM arsenite resulted in a 60% decrease in the amount of ERalpha and in a
parallel decrease of 40% in ERalpha messenger RNA. Progesterone receptor
concentration increased 22-fold after arsenite treatment. pS2 messenger RNA also
increased 2. 1-fold after treatment. The induction of progesterone receptor and
pS2 was blocked by the antiestrogen ICI-182,780. In transient cotransfection
experiments of wild-type ERalpha and an estrogen response element-reporter
construct, arsenite stimulated chloramphenicol acetyltransferase (CAT) activity.
In growth assays, arsenite significantly stimulated the proliferation of MCF-7
cells compared with cells grown in estrogen-depleted medium. Addition of an
antiestrogen blocked growth stimulation by arsenite. In binding assays, arsenite
blocked the binding of estradiol to ERalpha (Ki = 5 +/- 0.5 nM; n = 3),
suggesting that the compound interacts with the hormone-binding domain of the
receptor. To determine whether interaction of arsenite with the hormone-binding
domain results in receptor activation, COS-1 cells were transiently cotransfected
with the chimeric receptors GAL-ER, which contains the hormone-binding domain of
ERalpha and the DNA-binding domain of the transcription factor GAL4, and a GAL4
responsive CAT reporter gene. Treatment of cells with estradiol or arsenite
resulted in a 4-fold increase in CAT activity. The effects of arsenite on the
chimeric receptor were blocked by the antiestrogen, suggesting that arsenite
activates ERalpha through an interaction with the hormone-binding domain of the
receptor. Transfection assays with ERalpha mutants identified C381, C447, H524,
and N532 as interaction sites of arsenite with the hormone-binding domain.
PMID- 11014214
TI - Cytological characterization of a pituitary folliculo-stellate-like cell line,
Tpit/F1, with special reference to adenosine triphosphate-mediated neuronal
nitric oxide synthase expression and nitric oxide secretion.
AB - An immortal nonhormone-producing cell line with a characteristic star-shaped
morphology, named Tpit/F1, was derived from an anterior pituitary gland of a
temperature-sensitive large T antigen transgenic mouse. To characterize Tpit/F1
cells, we performed cytological studies, which revealed that Tpit/F1 cells
express the messenger RNAs of neruonal nitric oxide (NO) synthase, S-100 protein,
basic fibroblast growth factor, and pituitary-restricted transcription factor.
The Tpit/F1 cells response to pituitary adenylate cyclase-activating peptide
comprised the stimulated secretion of interleukin-6. Furthermore, glucocorticoids
stimulate glutamine synthase production by Tpit/F1 cells. Considering these
cytological characteristics together with their morphology, we deduced that
Tpit/F1 cells are derived from pituitary folliculo-stellate (FS) cells. Our
cytophysiological analyses of Tpit/F1 cells revealed that intracellular Ca2+
increased dose dependently on ATP administration (0-100 microM), and that this
effect did not require the presence of extracellular Ca2+ and was not abolished
by treatment with gadolinium, a Ca2+ channel blocker. The ATP-induced increase in
intracellular Ca2+ ([Ca2+]i) was completely abolished by treatment with the Ca2+
adenosine triphosphatase (Ca2+-ATPase) inhibitor thapsigargin, which suggests
that ATP increases [Ca2+]i by mobilizing internally stored Ca2+ followed by an
influx of Ca2+. Moreover, UTP was equipotent with ATP in causing the [Ca2+]i
increase in Tpit/F1 cells. Also, the Ca2+ response was prevented by the
phospholipase C inhibitor, U-73122, but not by its inactive analog, U-73343. From
these results we therefore concluded that ATP acts on Tpit/F1 cells via P2Y2
purinoceptors. Interestingly, both neuronal nitric oxide synthase messenger RNA
and NO secretion were increased by ATP administration (10 and 100 microM). These
results suggest the biological significance of the topological colocalization of
FS cells and endocrine cells. Namely, ATP is cosecreted with hormones from
endocrine cells and stimulates NO production by FS cells, and the released NO may
regulate neighboring endocrine cell and blood vessels.
PMID- 11014215
TI - Transcriptional down-regulation of human gonadotropin-releasing hormone (GnRH)
receptor gene by GnRH: role of protein kinase C and activating protein 1.
AB - Clinical applications of GnRH agonists (GnRHa) are based primarily on the
decrease in gonadotropin release after down-regulation of the GnRH receptor
(GnRHR) by continuous GnRHa administration. However, the molecular mechanisms
underlying the transcriptional regulation of the human GnRHR gene after prolonged
GnRH treatment remain poorly understood. In the present study GnRHa-mediated
regulation of human GnRHR gene transcription was studied by transiently
transfecting the mouse gonadotrope-derived (alphaT3-1) cells with a 2297-bp human
GnRHR promoter-luciferase construct (p2300-LucF). A dose- and time-dependent
decrease in human GnRHR promoter activity was observed after GnRHa treatment. An
average 71% decrease in promoter activity was observed after 24-h treatment with
0.1 microM GnRHa, which was blocked by cotreatment of the GnRH antagonist,
antide. This effect was mimicked by phorbol 12-myristate 13-acetate (TPA)
administration. In addition, the GnRHa- and TPA-mediated decrease in the human
GnRHR promoter activity was reversed by a specific protein kinase C (PKC)
inhibitor, GF109203X, or depletion of PKC by TPA pretreatment. These findings
indicate that the activation of the PKC pathway is important in regulating the
human GnRHR gene expression. By progressive 5'-deletion studies, we have
identified a 248-bp DNA fragment (-1018 to -771, relative to the translation
start site) at the 5'-flanking region of the human GnRHR gene that is responsible
for the GnRHa-mediated down-regulation of human GnRHR promoter activity. Analysis
of this sequence reveals the existence of two putative activating protein-1 (AP
1) sites with 87% homology to the consensus sequence (5'-TGA(G/C)T(C/A)A-3'),
located at -1000 to -994 (5'-TTAGACA-3', in complementary orientation) and -943
to 937 (5'-TGAATAA-3'). Using competitive gel mobility shift assays, AP-1 binding
was observed within this 248-bp region. Site-directed mutation of the putative AP
1-binding site located at -1000 to -994 abolished the GnRHa-induced inhibition.
Further competitive GMSA and supershift experiments confirmed the identity of AP
1 binding in this region. By the use of Western blot analysis, a significant
increase in c-Jun (100%; P < 0.05) and c-Fos (50%; P < 0.05) protein levels was
observed after GnRHa treatment in alphaT3-1 cells. In addition, our data
suggested that a change in AP-1 composition, particularly c-Fos, was important in
mediating GnRHa-induced inhibition of human GnRHR gene expression. We conclude
that activation of the PKC pathway by GnRH is important in controlling human
GnRHR gene expression. In addition, the putative AP-1-binding site located at
1000 to -994 of the human GnRHR5'-flanking region has been functionally
identified to be involved in mediating this down-regulatory effect.
PMID- 11014216
TI - Nicotine up-regulates expression of orexin and its receptors in rat brain.
AB - Orexins are two recently discovered neuropeptides that can stimulate food intake.
As the chronic use of tobacco typically leads to a reduction in body weight, it
is of interest to determine whether nicotine, the major biologically active
tobacco ingredient, has an effect on orexin metabolism in the brain. Using a
semiquantitative RT-PCR technique, the levels of messenger RNA (mRNA) for prepro
orexin, orexin A (OX1-R) and orexin B (OX2-R) receptors were 20-50% higher in
rats receiving nicotine for 14 days at the level of 2-4 mg/kg day compared with
rats receiving saline solvent alone. In animals treated with nicotine at 4 mg/kg
x day, the expression levels of mRNA for prepro-orexin, OX1-R, and OX2-R were
significantly higher compared with those in either the free-feeding control or
pair-fed saline control rats. RIA data indicated that both orexin A and orexin B
peptide levels were significantly elevated (45-54%; P < 0.01) in the dorsomedial
nucleus (DMH) of the nicotine-treated rats compared with either solvent-only or
pair-fed controls. Additionally, orexin B was significantly elevated (83%; P <
0.01), over levels in both types of the control animals, in the paraventricular
nucleus (PVN) region. In summary, we demonstrated that an inverse association
between nicotine and food intake as well as body weight held with doses
comparable to those consumed by average human smokers. Moreover, our data
indicated that chronic exposure to nicotine can induce a long-term increase in
the expression levels of prepro-orexin and their receptor mRNA in the rat
hypothalamus and in the levels of orexin A in the DMH and orexin B in the DMH and
PVN among the six hypothalamic regions that we examined.
PMID- 11014217
TI - Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and
diabetes.
AB - We previously demonstrated that the expression and function of the adipocyte
specific beta3-adrenergic receptor (beta3AR) are significantly depressed in
single gene and diet-induced rodent models of obesity. Furthermore, these models
are relatively unresponsive to the anti-obesity effects of beta3AR agonists.
Because all of these models are hyperinsulinemic, we hypothesized that
hyperinsulinemia could be responsible for this abnormality in beta3AR function.
The goal of this study was to determine whether lowering insulin with the K-ATP
channel agonist, diazoxide (Dz) would reverse the depressed expression and
function of the beta3AR found in a model of diet-induced diabetes and obesity in
C57BL/6J (B6) mice. B6 male mice were placed on either high fat (HF) or low fat
experimental diets. After 4 weeks, HF-fed mice were assigned to a group: HF or HF
containing disodium (R,R)-5- [2-( [2-(3-chlorophenyl)-2-hydroxyethyl]
amino]propyl-1,3-benzodioxole-2,2-di carboxylate (CL; 0.001%, wt/wt), Dz (0.32%,
wt/wt), or their combination (CLDz). Dz animals exhibited significantly reduced
plasma insulin levels as well as increased 3pAR expression and agonist-stimulated
adenylyl cyclase activity in adipocytes. CLDz was more effective in reducing
percent body fat, lowering nonesterified fatty acids, improving glucose
tolerance, and reducing feed efficiency than either treatment alone.
PMID- 11014218
TI - Expression of enzymes synthesizing (aldehyde dehydrogenase 1 and reinaldehyde
dehydrogenase 2) and metabolizaing (Cyp26) retinoic acid in the mouse female
reproductive system.
AB - Vitamin A is required for female reproduction. Rodent uterine cells are able to
synthesize retinoic acid (RA), the active vitamin A derivative, and express RA
receptors. Here, we report that two RA-synthesizing enzymes [aldehyde
dehydrogenase 1 (Aldh1) and retinaldehyde dehydrogenase 2 (Raldh2)] and a
cytochrome P450 (Cyp26) that metabolizes vitamin A and RA into more polar
metabolites exhibit dynamic expression patterns in the mouse uterus, both during
the ovarian cycle and during early pregnancy. Aldh1 expression is up-regulated
during diestrus and proestrus in the uterine glands, whereas Raldh2 is highly
induced in the endometrial stroma in metestrus. Cyp26 expression, which is not
detectable during the normal ovarian cycle, is strongly induced in the uterine
luminal epithelium, 24 h after human CG hormonal administration. Raldh2 stromal
expression also strongly responds to gonadotropin (PMSG and human CG) induction.
Furthermore, Raldh2 expression can be hormonally induced in stromal cells of the
vagina and cervix. All three enzymes exhibit differential expression profiles
during early pregnancy. Aldh1 glandular expression is sharply induced at 2.5
gestational days, whereas Raldh2 stromal expression increases more steadily until
the implantation phase. Cyp26 epithelial expression is strongly induced between
3.5-4.5 gestational days, i.e. when the developing blastocysts colonize the
uterine lumen. These data suggest a need for precise regulation of RA synthesis
and/or metabolism, in both cycling and pregnant uterus.
PMID- 11014219
TI - Antiinflammatory effects of estrogen on microglial activation.
AB - In the present study the effects of 17beta-estradiol on microglial activation are
described. Estrogen replacement therapy has been associated with decreased
severity of age-related neurodegenerative diseases such as Alzheimer's disease,
and estrogens have potent immunosuppressive properties outside of the brain. To
determine the role that microglial cells might play in estrogen-mediated
neuroprotection, primary rat microglia and N9 microglial cell lines were treated
with increasing doses of 17beta-estradiol before or during immunostimulation by
lipopolysaccharide, phorbol ester, or interferon-gamma. Pretreatment with 17beta
estradiol, but not 17alpha-estradiol or progesterone, dose dependently attenuated
microglial superoxide release and phagocytic activity. Additionally, 17beta
estradiol attenuated increases in inducible nitric oxide synthase protein
expression, but did not alter nuclear factor-KB activation. The antiinflammatory
effects of 17beta-estradiol were blocked by the antiestrogen ICI 182,780.
Additionally, 17beta-estradiol induced rapid phosphorylation of the p42/p44
mitogen-activated protein kinase (MAP kinase), and the MAP kinase inhibitor PD
98059 blocked the antiinflammatory effects of 17beta-estradiol. Overall, these
results suggest that estrogen receptor-dependent activation of MAP kinase is
involved in estrogen-mediated antiinflammatory pathways in microglial cells.
These results describe a novel mechanism by which estrogen may attenuate the
progression of neurodegenerative disease and suggest new pathways for therapeutic
intervention in clinical settings.
PMID- 11014220
TI - Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and
beta.
AB - Epidemiological evidence indicates that phytoestrogens inhibit cancer formation
and growth, reduce cholesterol levels, and show benefits in treating
osteoporosis. At least some of these activities are mediated through the
interaction of phytoestrogens with estrogen receptors alpha and beta (ERalpha and
ERbeta). Resveratrol, trans-3,5,4'-trihydroxystilbene, is a phytoestrogen in
grapes that is present in red wine. Resveratrol was shown to bind ER in cytosolic
extracts from MCF-7 and rat uteri. However, the contribution of ERalpha vs.
ERbeta in this binding is unknown. Here we report that resveratrol binds ERbeta
and ERalpha with comparable affinity, but with 7,000-fold lower affinity than
estradiol (E2). Thus, resveratrol differs from other phytoestrogens that bind
ERbeta with higher affinity than ERalpha. Resveratrol acts as an estrogen agonist
and stimulates ERE-driven reporter gene activity in CHO-K1 cells expressing
either ERalpha or ERbeta. The estrogen agonist activity of resveratrol depends on
the ERE sequence and the type of ER. Resveratrol-liganded ERbeta has higher
transcriptional activity than E2-liganded ERbeta at a single palindromic ERE.
This indicates that those tissues that uniquely express ERbeta or that express
higher levels of ERbeta than ERalpha may be more sensitive to resveratrol's
estrogen agonist activity. For the natural, imperfect EREs from the human c-fos,
pS2, and progesterone receptor (PR) genes, resveratrol shows activity comparable
to that induced by E2. We report that resveratrol exhibits E2 antagonist activity
for ERalpha with select EREs. In contrast, resveratrol shows no E2 antagonist
activity with ERbeta. These data indicate that resveratrol differentially affects
the transcriptional activity of ERalpha and ERbeta in an ERE sequence-dependent
manner.
PMID- 11014221
TI - Neuroendocrine cell type-specific and inducible expression of the chromogranin B
gene: crucial role of the proximal promoter.
AB - Chromogranin B, a soluble acidic secretory protein, is widely distributed in
neuroendocrine and neuronal cells, although not in other cell types. To identify
the elements governing such widespread, yet selective, expression of the gene, we
characterized the isolated mouse chromogranin B promoter. 5'-Promoter deletions
localized neuroendocrine cell type-specific expression to the proximal
chromogranin B promoter (from -216 to -91 bp); this region contains an E box (at
[-206 bp]CACCTG[-201 bp]), four G/C-rich regions (at [-196 bp]CCCCGC[-191 bp], [
134 bp]CCGCCCGC[-127 bp], [-125 bp]GGCGCCGCC[-117 bp], and [-115 bp]CGGGGC[-110
bp]), and a cAMP response element (CRE; at [-102 bp]TGACGTCA[-95 bp]). A 60-bp
core promoter region, defined by an internal deletion from - 134 to -74 bp
upstream of the cap site and spanning the CRE and three G/C-rich regions,
directed tissue-specific expression of the gene. The CRE motif directed cell type
specific expression of the chromogranin B gene in neurons, whereas three of the
G/C-rich regions played a crucial role in neuroendocrine cells. Both the
endogenous chromogranin B gene and the transfected chromogranin B promoter were
induced by preganglionic secretory stimuli (pituitary adenylyl cyclase-activating
polypeptide, vasoactive intestinal peptide, or a nicotinic cholinergic agonist),
establishing stimulus-transcription coupling for this promoter. The adenylyl
cyclase activator forskolin, nerve growth factor, and retinoic acid also
activated the chromogranin B gene. Secretagogue-inducible expression of
chromogranin B also mapped onto the proximal promoter; inducible expression was
entirely lost upon internal deletion of the 60-bp core (from 134 to -74 bp). We
conclude that CRE and G/C-rich domains are crucial determinants of both cell type
specific and secretagogue-inducible expression of the chromogranin B gene.
PMID- 11014222
TI - Transforming growth factor-beta2 mediates mesenchymal-epithelial interactions of
testicular somatic cells.
AB - Transforming growth factor-beta2 (TGFbeta2) is an important mediator of growth
and differentiation. We here describe for the first time the complete sequence of
the TGFbeta2 complementary DNA derived from peritubular myoid cells of the rat
testis. The size of the rat TGFbeta2 complementary DNA was 1245 bp, and the
deduced protein sequence contained 414 amino acids. Sequence comparison with the
human and mouse amino acid sequences demonstrated 96.4% and 97.9% sequence
identities, respectively. To elucidate the functional role of TGFbeta2 in
testicular somatic cells, we studied its secretion in vitro in monocultures and
cocultures of mesenchymal peritubular and epithelial Sertoli cells. The highest
amounts of TGFbeta2 protein were secreted in the cocultures and by peritubular
cells, whereas Sertoli cells secreted only minor amounts. Stimulation experiments
with FSH revealed a reduced secretion of TGFbeta2 in cocultures, probably
mediated by a paracrine interaction of the FSH-responsive Sertoli cells. In
contrast, TGFbeta2 secretion by peritubular cells was increased after stimulation
with glucocorticoids and after addition of recombinant TGFbeta2, indicating an
autoregulation of TGFbeta2. Furthermore, application of recombinant TGFbeta2 to
cocultures resulted in an enhanced aggregation and cell clustering of Sertoli
cells, pointing to an important role of TGFbeta2 in the paracrine interaction of
peritubular and Sertoli cells of the developing rat testis.
PMID- 11014223
TI - Potentiation of growth hormone-induced liver suppressors of cytokine signaling
messenger ribonucleic acid by cytokines.
AB - Endotoxin and proinflammatory cytokines such as interleukin-1beta (IL-1beta) and
tumor necrosis factor-alpha (TNFalpha) induce a state of GH resistance. A new
family of suppressors of cytokine signaling (SOCS), induced by cytokines
activating the Janus kinase (JAK)-signal transducer and activator of
transcription (STAT) pathway, has been recently identified as a negative feedback
loop of intracellular signaling. Overexpression of some SOCS (SOCS-3, CIS, and
SOCS-2) has been reported to inhibit the JAK-STAT pathway stimulated by GH. To
assess the possible role of these three SOCS proteins in the GH resistance
induced by endotoxin and cytokines, we investigated the regulation of their gene
expression by endotoxin and GH in rat liver and by proinflammatory cytokines and
GH in primary culture hepatocytes. Both GH and lipopolysaccharide induced the
three SOCS messenger RNAs (mRNAs) in vivo. In vitro, GH also increased the liver
mRNAs encoding SOCS-2, SOCS-3, and CIS. Although IL-1/beta and TNFalpha alone
induced only weakly the expression of SOCS-3 and CIS, these cytokines strongly
potentiated the induction of these two SOCS by GH. In contrast, IL-6 alone
markedly induced SOCS-3 mRNA, but did not potentiate the GH action on SOCS-3 and
CIS mRNAs. The GH induction of SOCS-2 was not potentiated by any of these
cytokines. Considering the ability of these SOCS to inhibit the JAK-STAT pathway
induced by GH, these results suggest that the overexpression of SOCS-3 and CIS
mRNAs induced by IL-1beta and TNFalpha or by endotoxin in vivo may play a role in
the GH resistance induced by sepsis.
PMID- 11014224
TI - Induction of calcitonin and calcitonin receptor expression in rat mammary tissue
during pregnancy.
AB - Human breast milk samples at early time points after parturition contain high
levels of calcitonin (CT) in both normal and thyroidectomized mothers, suggesting
that mammary tissue produces CT. Using blot hybridization and reverse
transcriptase polymerase chain (RT-PCR) analysis of rat mammary RNA we found that
CT messenger RNA is induced at midpregnancy (day 12), remains elevated through
late pregnancy (day 19) but then decreases before the day of birth. RIA of
mammary CT revealed that levels increase from 0.3 ng/g tissue in nonpregnant
animals to peak at 1.6 ng/g on day 19 and then decline after that, paralleling
messenger RNA expression. Dilution profiles for extracted mammary CT showed close
parallelism with monomeric rat CT. Plasma samples from thyroparathyroidectomized
rats contained 10-20 pg/ml CT that did not increase during pregnancy, suggesting
that mammary CT is not released into plasma but functions locally. Consistent
with this, RT-PCR detected that the CT receptor C1a isoform is expressed in rat
mammary tissues during both pregnancy and lactation. This is the first report
that mammary tissue expresses both CT and the CT receptor during pregnancy,
suggesting that CT may have a paracrine regulatory role in the mammary gland.
PMID- 11014225
TI - Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide,
regulates fasting glycemia and nonenteral glucose clearance in mice.
AB - Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide
(GIP) potentiate glucose-stimulated insulin secretion after enteral nutrient
ingestion. We compared the relative incretin and nonincretin actions of GLP-1 and
GIP in +/+ and GLP-1R-/- mice using exendin(9-39) and immunopurified anti-GIP
receptor antisera (GIPR Ab) to antagonize GLP-1 and GIP action, respectively.
Both antagonists produced a significant increase in glycemic excursion after oral
glucose loading of +/+ mice (P < 0.05 for antagonists us. controls). Exendin(9
39) also increased blood glucose and decreased glucose-stimulated insulin in +/+
mice after ip glucose loading [0.58 +/- 0.02 vs. 0.47 +/- 0.02 ng/ml in saline-
vs. exendin(9-39)-treated mice, respectively, P < 0.05]. In contrast, GIPR Ab had
no effect on glucose excursion or insulin secretion, after ip glucose challenge,
in +/+ or GLP-1R-/- mice. Repeated administration of exendin(9-39) significantly
increased blood glucose and reduced circulating insulin levels but had no effect
on levels of pancreatic insulin or insulin messenger RNA transcripts. In
contrast, no changes in plasma glucose, circulating insulin, pancreatic insulin
content, or insulin messenger RNA were observed in mice, 18 h after
administration of GIPR Ab. These findings demonstrate that GLP-1, but not GIP,
plays an essential role in regulating glycemia, independent of enteral nutrient
ingestion in mice in vivo.
PMID- 11014226
TI - Glucose-dependent insulinotropic polypeptide confers early phase insulin release
to oral glucose in rats: demonstration by a receptor antagonist.
AB - A novel GIP receptor antagonist was developed to evaluate the acute role of
glucose-dependent insulinotropic polypeptide (GIP) in the insulin response to
oral glucose in rats. Antisera to an extracellular epitope of the GIP receptor
(GIPR) detected immunoreactive GIPR on rat pancreatic beta-cells. Purified GIPR
antibody (GIPR Ab) specifically displaced GIP binding to the receptor and blocked
GIP-mediated increases in intracellular cAMP. When delivered to rats by ip
injection, GIPR Ab had a half-life of approximately 4 days. Treatment with GIPR
Ab (1 microg/g BW) blocked the potentiation of glucose-stimulated insulin
secretion by GIP (60 pmol) but not glucagon-like peptide-1 (GLP-1, 60 pmol) in
anesthetized rats. The insulin response to oral glucose was delayed in conscious
unrestrained rats that were pretreated with GIPR Ab. Plasma insulin levels were
approximately 35% lower at 10 min in GIPR Ab treated animals compared with
controls. As a result, the glucose excursion was greater in the GIPR Ab treated
group. Fasting plasma glucose levels were not altered by GIPR Ab. We conclude
that release of GIP following oral glucose may act as an anticipatory signal to
pancreatic beta-cells to promote rapid release of insulin for glucose disposal.
PMID- 11014227
TI - Juxtamembrane regions in the third intracellular loop of the thyrotropin
releasing hormone receptor type 1 are important for coupling to Gq.
AB - Juxtamembrane residues in the putative third intracellular (I3) loops of a number
of G protein-coupled receptors (GPCRs) have been shown to be important for
coupling to G proteins. According to standard hydropathy analysis, the I3 loop of
the mouse TRH receptor type 1 (mTRH-R1) is composed of 51 amino acids from
position-213 to position-263. We constructed deletion and site-specific I3 loop
TRH-R mutants and studied their binding and TRH-stimulated signaling activities.
As expected, the effects of these mutations on TRH binding were small (less than
5-fold decreases in affinity). No effect on TRH-stimulated signaling activity was
found in a mutant receptor in which the I3 loop was shortened to 16 amino acids
by deleting residues from Asp-226 to Ser-260. In contrast, mutants with deletions
from Asp-222 to Ser-260 or from Asp-226 to Gln-263 exhibited reduced TRH
stimulated signaling. In the region near transmembrane helix 6, single site
specific substitution of either Arg-261 or Lys-262 by neutral glutamine had
little effect on signaling, but mutant TRH-Rs that were substituted by glutamine
at both basic residues exhibited reduced TRH-stimulated activity. The reduced
signaling activity of this doubly substituted mutant was reversed by over
expressing the a subunit of Gq. These data demonstrate that the juxtamembrane
regions in the TRH-R I3 loop are important for coupling to Gq.
PMID- 11014228
TI - Pituitary adenylate cyclase-activating polypeptide precursor is processed solely
by prohormone convertase 4 in the gonads.
AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is abundant not only
in the brain, but also in the testis. Immunohistochemical studies have shown that
PACAP-LI in rat testis is expressed stage specifically in spermatids. This
suggests that testicular PACAP participates in the regulatory mechanism of
spermatogenesis. Additionally, the ovary contains a relatively small amount of
PACAP, conceivably involved in the regulation of folliculogenesis. PACAP is
synthesized as a preprohormone and is processed by prohormone convertases, such
as PC1, PC2, and PC4. PC4 is expressed only in the testis and ovary, where
neither PC1 nor PC2 is expressed. However, whether PC4 is the sole endoprotease
for the PACAP precursor in the gonads remains unknown. Recent studies using PC4
transgenic mice revealed that male PC4-null mice exhibited severely impaired
fertility, although spermatogenesis appeared to be normal. The female PC4-null
mice exhibited delayed folliculogenesis in the ovaries. To examine whether PC4 is
the sole processing enzyme for the PACAP precursor in the gonads, we analyzed
testicular and ovarian extracts from the PC4-null and wild-type mice for PACAP
(PACAP38 and PACAP27) and its messenger RNA using reverse phase HPLC combined
with specific RIAs and ribonuclease protection assay, respectively. For RIAs,
three different polyclonal antisera with different recognition sites were used to
identify PACAP38, PACAP27, and its precursor. Neither the testis nor the ovary
from the PC4-null mice expressed PACAP38 or PACAP27, but the levels of PACAP
transcripts in the testis and ovary of homozygous PC4-deficient mice were
considerably elevated compared with those of the wild-type and heterozygous
animals. The findings indicate that PC4 is the sole processing enzyme for the
precursor of PACAP in the testis and ovary of mice. The possibility that the
absence of bioactive PACAP in the testis and ovary of PC4-null mice caused
severely impaired fertility in the males and delayed folliculogenesis in females
warrants investigation.
PMID- 11014229
TI - Whole-cell recordings from preoptic/hypothalamic slices reveal burst firing in
gonadotropin-releasing hormone neurons identified with green fluorescent protein
in transgenic mice.
AB - Central control of reproduction is governed by a neuronal pulse generator that
underlies the activity of hypothalamic neuroendocrine cells that secrete GnRH.
Bursts and prolonged episodes of repetitive action potentials have been
associated with hormone secretion in this and other neuroendocrine systems. To
begin to investigate the cellular mechanisms responsible for the GnRH pulse
generator, we used transgenic mice in which green fluorescent protein was
genetically targeted to GnRH neurons. Whole-cell recordings were obtained from 21
GnRH neurons, visually identified in 200-microm preoptic/hypothalamic slices, to
determine whether they exhibit high frequency bursts of action potentials and are
electrically coupled at or near the somata. All GnRH neurons fired spontaneous
action potentials, and in 15 of 21 GnRH neurons, the action potentials occurred
in single bursts or episodes of repetitive bursts of high frequency spikes (9.77
+/- 0.87 Hz) lasting 3-120 sec. Extended periods of quiescence of up to 30 min
preceded and followed these periods of repetitive firing. Examination of 92 GnRH
neurons (including 32 neurons that were located near another green fluorescent
protein-positive neuron) revealed evidence for coupling in only 1 pair of GnRH
neurons. The evidence for minimal coupling between these neuroendocrine cells
suggests that direct soma to soma transfer of information, through either
cytoplasmic bridges or gap junctions, has a minor role in synchronization of GnRH
neurons. The pattern of electrical activity observed in single GnRH neurons
within slices is temporally consistent with observations of GnRH release and
multiple unit electrophysiological correlates of LH release. Episodes of burst
firing of individual GnRH neurons may represent a component of the GnRH pulse
generator.
PMID- 11014231
TI - Selective involvement of interleukin-6 in the transcriptional activation of the
suppressor of cytokine signaling-3 in the brain during systemic immune
challenges.
AB - Cytokine-inducible proteins named as suppressors of cytokine signaling (SOCS) are
rapidly induced by interleukin-6 (IL-6) and other members sharing the gp130
receptor subunit after activation of the Janus kinases (JAK) and the signal
transducers and activators of transcription (STAT). These inhibitory proteins
generally prevent tyrosine phosphorylation of IL-6 receptor signaling subunit
gp130, specific JAK and STAT or in acting at steps distal to JAK activation.
Expression of these inhibitory proteins is therefore a useful tool to investigate
the signaling events occurring in the brain during immunogenic stimuli that
involve cytokines of the IL-6 family. This study investigated the effect of ip
lipopolysaccharide (LPS) administration on the expression of one key member of
the SOCS family, SOCS-3, in both rats and mice. In rats, the endotoxin caused a
profound transcriptional activation of the inhibitory factor in the
circumventricular organs subfornical organ, organum vasculosum of the lamina
terminalis, arcuate nucleus/median eminence, area postrema, choroid plexus,
leptomeninges, ependymal lining cells, and along the endothelium of the brain
blood vessels. The hybridization signal for SOCS-3 messenger RNA was low at 1 h,
but robust at 3 and 6 h and declined to return to basal levels 12 h after the
single ip LPS injection. The pattern of SOCS-3 expression was similar in the
brain of wild-type mice, although induction of the inhibitory factor was no
longer observed in the ependymal lining cells of the cerebral ventricles and the
blood microvessels of IL-6-deficient animals at all the times evaluated, i.e.
from 1-8 h post-LPS injection. The endothelium of the brain capillaries also
exhibited up-regulation of both IL-6 receptor and gp130 subunits during systemic
inflammation, which allowed SOCS-3 expression in response to circulating IL-6.
The present data indicate that the JAK/STAT transduction pathways that lead to
SOCS-3 transcription are activated within cells accessible from the blood
circulation, but not within deep parenchymal elements of the brain during
endotoxemia. Induction of SOCS-3 followed the cascade of events that take place
during the acute phase response and the contribution of IL-6 in activating the
inhibitory factor is site specific and not generalized throughout the central
nervous system.
PMID- 11014230
TI - Promoter elements and transcription factors involved in differentiation-dependent
human chorionic gonadotrophin-alpha messenger ribonucleic acid expression of term
villous trophoblasts.
AB - Differentiation of primary villous cytotrophoblasts into syncytia is associated
with increasing production of alpha and beta human CG subunits, which is
predominantly governed at the level of messenger RNA expression. Here, we present
a detailed study on the mechanisms involved in the differentiation-dependent
regulation of the trophoblast-specific CGalpha gene promoter. Site-directed
mutations in each of the five DNA-elements of the composite enhancer were
performed to investigate the contribution of the individual regulatory sequences
to the overall transcriptional activity of the promoter at two different stages
of trophoblast in vitro differentiation. We show that deletion of one cyclic AMP
response element (CRE) did not affect CGalpha promoter activity in
cytotrophoblasts; however, it reduced transcription by 33% in differentiating
cultures. Removal of both CREs almost abolished transcription at early and later
stages of in vitro differentiation. Upon mutation the enhancer elements alphaACT,
JRE, and CCAAT significantly decreased luciferase reporter transcription; however
their contribution to the total promoter activity did not change during in vitro
differentiation. Contrary to that, mutated TSE diminished promoter activity by
19% during 12 and 48 h of cultivation but reduced luciferase expression by 78%
between 48 and 84 h of differentiation. In electrophoretic mobility shift assay,
the TSE interacted with activating protein (AP)-2alpha in both primary
trophoblasts and choriocarcinoma cells. While CRE-interacting proteins were
detectable 12 h after isolation, the TSE-binding complex did not appear before 36
h of in vitro differentiation. During syncytium formation increasing protein
expression of activating transcription factor (ATF)-1, cAMP response element
binding protein (CREB)-1, and AP-2alpha was observed on Western blots. Moreover,
phosphorylated CREB-1 and ATF-1 accumulated between 24 and 78 h of trophoblast
cultivation. By fluorescence immunohistochemistry, we show that CREB-1 was
predominantly expressed in syncytiotrophoblasts, whereas ATF-1 and AP-2alpha
localized to the syncytium and some cytototrophoblasts as well as to stromal and
endothelial cells of the placental villus. Phosphorylated CREB-1/ATF-1 and the
coactivator protein CBP were primarily detected in syncytial nuclei, suggesting
the presence of functional, cAMP-dependent transcriptional complexes in the
differentiated tissue. In agreement to the in vivo situation, phosphorylated CREB
1/ATF-1 were observed in nuclei of the differentiated trophoblast cultures. The
activity of the CGalpha promoter as well as CREB-1/ATF-1 phosphorylation
increased upon elevation of cAMP levels and overexpression of the catalytic
subunit of protein kinase A. Additionally, we demonstrate that overproduction of
the enzyme enhanced protein expression and binding of AP-2alpha to the TSE. We
conclude that differentiation-dependent transcription of the CGalpha gene in
villous trophoblasts is mainly governed by increasing expression of AP-2alpha and
PKA-dependent phosphorylation of CREB-1 and ATF-1.
PMID- 11014232
TI - Functional significance of MMP-9 in tumor necrosis factor-induced proliferation
and branching morphogenesis of mammary epithelial cells.
AB - Tissue remodeling is a key process involved in normal mammary gland development,
with matrix metalloproteinases (MMPs) playing an important role in this process.
Our laboratory has demonstrated that tumor necrosis factor (TNF) stimulates
branching morphogenesis of mammary epithelial cells (MEC) within a reconstituted
basement membrane. Studies were therefore undertaken to determine whether MMPs
might mediate the effects of TNF. Using a primary culture model in which rat MEC
grow three-dimensionally within a reconstituted basement membrane, we found that
TNF stimulated secretion of MMP-9 but not MMP-2. To determine whether MMP-9 was
involved in TNF-induced proliferation and branching morphogenesis, we used a
peptide containing the prodomain sequence of MMPs and two MMP inhibitors. Both
the prodomain peptide (5 x 10(-4)-10(-3) M), as well as BB-94 (10(-8)-10(-5) M)
and CGS 27023A (10(-6)-10(-5) M), inhibited TNF-induced proliferation and
branching morphogenesis in a concentration-dependent manner. Finally, to verify
the specific requirement for MMP-9, we demonstrated that an MMP-9 neutralizing
antibody blocked TNF-induced proliferation and branching morphogenesis. Together,
these data suggest that TNF-regulated MMP-9 may play a role in the controlled
invasion of the fad pad that occurs during normal mammary gland development and
that misregulation of MMP-9 may contribute to the invasiveness of breast cancer.
PMID- 11014233
TI - Calcitonin receptor regulation and responsiveness to calcitonin in human
osteoclast-like cells prepared in vitro using receptor activator of nuclear
factor-kappaB ligand and macrophage colony-stimulating factor.
AB - Using mouse osteoclast-like cells (OCs), we have shown that short exposure to
calcitonin (CT) resulted in prolonged reduction of CT binding by inhibiting de
novo CT receptor (CTR) synthesis. Additionally, CT-treated OCs demonstrated
resistance to CT rechallenge on the inhibitory effect of CT in osteoclastic bone
resorption. There is, however, scant information on CT effects on human
osteoclasts. In this study, we examined the features of CTR down-regulation and
its recovery after short exposure to CT of human OCs. OCs were prepared by
treatment of peripheral blood mononuclear cells in vitro with osteoclast
differentiation factor and macrophage colony-stimulating factor. Treatment of OCs
with salmon CT (sCT) and human CT (hCT) resulted in a dose-dependent reduction in
[125I]sCT binding capacity. Continued receptor occupancy by ligand was excluded
by using a glycine-acid washing procedure. Treatment with sCT reduced CTR
messenger RNA expression, suggesting that CTR down-regulation is, at least
partly, attributable to an inhibition of de novo CTR synthesis. To investigate
the intracellular signal transduction pathways that mediate these effects, we
examined the effects of activation of the protein kinase (PK)A, PKC, and Ca2+
calmodulin-dependent kinases. Treatment with PKC activators mimicked CT, whereas
neither activation of PKA nor elevation of intracellular Ca2+ did so. We further
investigated the intracellular signaling pathways responsible for the inhibitory
effects of CT on bone resorption, which showed that treatment with PKC activators
reproduced the effects of CT. These data suggest that the PKC pathway plays an
important role in homologous CTR down-regulation, as well as inhibition of bone
resorbing activity by CT, in human OCs. Short exposure of OCs to CT (10(-9) M, 1
h) reduced [125I]sCT-specific binding for a prolonged period, as we have shown
previously in mouse OCs. The reduced specific binding, CTR messenger RNA levels,
and CT-sensitive adenylate cyclase responsiveness returned to the control levels
by 96 h after removal of CT. These results strongly support the notion that
escape from CT inhibition of osteoclastic bone resorption in humans is
attributable to the development of resistance by OCs to CT. This study also
showed that even short exposure to CT induced prolonged desensitization to CT
rechallenge, although the OCs eventually regained responsiveness to sCT
rechallenge.
PMID- 11014234
TI - Prostaglandin production at the onset of ovine parturition is regulated by both
estrogen-independent and estrogen-dependent pathways.
AB - A current hypothesis of ovine parturition proposes that fetal adrenal cortisol
induces placental E2 production, which, in turn, triggers intrauterine PG
production. However, recent evidence suggests that cortisol may directly increase
PG production in trophoblast-derived tissues. To separate cortisol-dependent and
estrogen-dependent PG production in sheep intrauterine tissues, we infused
singleton, chronically catheterized fetuses beginning on day 125 of gestation
(term, 147-150 days) with 1) cortisol (1.35 mg/h; n = 5); 2) cortisol and 4
hydroxyandrostendione, a P450aromatase inhibitor (4-OHA: 1.44 mg/h; n = 5); 3)
saline (n = 5); or 4) saline and 4-OHA (n = 5). Fetal and maternal arterial blood
samples were collected at 12-h intervals starting 24 h before infusion and
continuing during treatment for 80 h or until active labor. Uterine contractility
was measured by electromyogram recording of myometrial activity. Plasma E2,
progesterone (P4), PGE2, and 13,14-dihydro- 15-keto-PGF2alpha were quantified by
RIA. PGHS-II messenger RNA (mRNA) and protein expression were determined by in
situ hybridization and Western blot analysis, respectively. Data were analyzed by
ANOVA (P < or = 0.05). Labor-type uterine contractions were present after 68 h of
cortisol infusion and had increased significantly by 80 h. Labor-type uterine
contractions were induced after 68 h of cortisol plus 4-OHA infusion, but the
contraction frequency remained less than that in the cortisol-treated animals.
Fetal cortisol infusion increased fetal and maternal plasma E2 concentrations and
decreased the maternal plasma P4 concentration significantly; concurrent 4-OHA
infusion attenuated the increase in fetal and maternal plasma E2, but not the
decrease in maternal plasma P4. The fetal plasma PGE2 concentration increased
after both cortisol and cortisol plus 4-OHA infusion. The maternal plasma 13,14
dihydro-15-keto-PGF2alpha concentration rose after fetal cortisol infusion, but
not after cortisol plus 4-OHA infusion. Placental trophoblast PGHS-II mRNA and
protein expression were increased significantly after both cortisol and cortisol
plus 4-OHA infusion. Endometrial PGHS-II mRNA and protein expression increased
after cortisol infusion, but not after cortisol plus 4-OHA infusion. Plasma
steroid and PG concentrations, uterine activity pattern, and intrauterine PGHS-II
expression were not altered in either control group. We conclude that these data
suggest distinct pathways of intrauterine PG synthesis: a cortisol-dependent/E2
independent mechanism within trophoblast tissue leading to elevations in fetal
plasma PGE2, and an E2-dependent mechanism within maternal endometrium that leads
to increased maternal plasma PGF2alpha and appears necessary for uterine activity
and parturition.
PMID- 11014235
TI - The differential fate of mesonephric tubular-derived efferent ductules in
estrogen receptor-alpha knockout versus wild-type female mice.
AB - We investigated mesonephric tubular-derived efferent ductules in female wild-type
(WT) and estrogen receptor-alpha knockout (ERalphaKO) mice from late fetal to
adult life. On gestational day 17, efferent ductules in both fetal WT and
ERalphaKO females were well developed and morphologically similar, although one
third the size of the male counterpart. Unexpectedly, efferent ductules with a
ciliated epithelium were still present on postnatal day 10 in WT and ERalphaKO
females. By day 23, however, marked phenotypic differences occurred in efferent
ductules of WT and ERbetaKO vs. ERalphaKO female mice. In the latter, efferent
ductules became hypertrophied and dilated, whereas only small tubules remained in
WT and ERbetaKO adult mice. The serum testosterone concentrations were similar in
21- to 25-day-old ERalphaKO, heterozygous, and WT female mice, suggesting that
increased testosterone was not inducing enlargement of efferent ductules in
ERalphaKO females. In conclusion, remnants of efferent ductules persisted in
normal adult female mice, although these structures were greatly reduced in size
compared with efferent ductules in ERalphaKO female mice. The underlying
mechanism inducing hypertrophy and dilation of efferent ductules in ERalphaKO
females is not clear, but secretory and/or reabsorptive function of female
efferent ductules may involve ERalpha.
PMID- 11014236
TI - Circadian and glucocorticoid regulation of Rev-erbalpha expression in liver.
AB - Rev-erbalpha [NR1D1], a member of the nuclear receptor superfamily, is an orphan
receptor that constitutively represses gene transcription. Rev-erbalpha has been
shown to play a role in myocyte differentiation and to be induced during
adipogenesis. Furthermore, Rev-erbalpha is a regulator of lipoprotein metabolism.
It was recently shown that Rev-erbalpha messenger RNA (mRNA) levels oscillate
diurnally in rat liver. Here, we report that the circadian rhythm of Rev-erbalpha
in liver is maintained in primary cultures of rat hepatocytes. Because
glucocorticoids have been shown to regulate other transcription factors with
circadian expression, it was furthermore examined whether hepatic Rev-erbalpha
expression is also regulated by glucocorticoids. Treatment of rats with
dexamethasone resulted in a decrease of Rev-erbalpha mRNA levels by 70% after 6
h. Furthermore, dexamethasone decreased Rev-erbalpha expression in rat primary
hepatocytes in a dose-dependent fashion. This effect was mediated by the
glucocorticoid receptor because simultaneous addition of the glucocorticoid
antagonist RU486 prevented the decrease in Rev-erbalpha mRNA levels by
dexamethasone. Protein synthesis inhibition with cycloheximide markedly induced
Rev-erbalpha mRNA levels; however, this induction was reduced by dexamethasone
supplementation in both rat and human primary hepatocytes. Treatment with
actinomycin D blocked the repression of Rev-erbalpha expression by dexamethasone
in rat hepatocytes, suggesting that glucocorticoids regulate Rev-erbalpha
expression at the transcriptional level. Transient transfection experiments
further indicated that Rev-erbalpha promoter activity is repressed by
dexamethasone in the presence of cotransfected glucocorticoid receptor. Taken
together, these data demonstrate that Rev-erbalpha expression is under the
control of both the circadian clock and glucocorticoids in the liver.
PMID- 11014237
TI - Genetic models reveal that brain natriuretic peptide can signal through different
tissue-specific receptor-mediated pathways.
AB - Brain natriuretic peptide (BNP), a hormone produced primarily by the cardiac
ventricle, is thought to be involved in a variety of homeostatic processes
through its cognate receptor, guanylyl cyclase A (GC-A). We previously created
transgenic mice overexpressing BNP under the control of the liver-specific human
serum amyloid P component promoter (BNP-transgenic mice) and demonstrated that
they exhibit reduced blood pressure and cardiac weight accompanied by an
elevation of plasma cGMP concentrations and marked skeletal overgrowth through
the activation of endochondral ossification. To address whether BNP exerts its
biological effects solely through GC-A, we produced BNP-transgenic mice lacking
GC-A (BNP-Tg/GC-A-/- mice) and examined their cardiovascular and skeletal
phenotypes. The GC-A-/- mice are hypertensive with cardiac hypertrophyrelative to
wild-type littermates, which is not alleviated by overexpression of BNP in BNP
Tg/GC-A-/- mice. The BNP-Tg/GC-A-/- mice, however, continue to exhibit marked
longitudinal growth of vertebrae and long bones comparably to BNP-Tg mice. This
study provides genetic evidence that BNP reduces blood pressure and cardiac
weight through GC-A, whereas it dramatically alters endochondral ossification in
the absence of this receptor. Therefore, the BNP-Tg/GC-A-/- mice provide the
first experimental model demonstrating that this natriuretic peptide can signal
in a tissue-specific manner through a receptor other than GC-A.
PMID- 11014238
TI - In vivo treatment with GDF-9 stimulates primordial and primary follicle
progression and theca cell marker CYP17 in ovaries of immature rats.
AB - Growth differentiation factor (GDF)-9 is a cystine knot-containing hormone of the
transforming growth factor-beta superfamily produced by the oocyte. In GDF-9 null
mice, follicle development is arrested at the primary stage and GDF-9 treatment
in vitro enhances preantral follicle growth. Immature female rats were treated
with recombinant GDF-9 for 7 or 10 days. At 10 days, treatment with GDF-9
augmented ovarian weights, concomitant with an increase in the number of primary
and small preantral follicles by 30 and 60%, respectively. Furthermore, the
number of primordial follicles was decreased by 29%, but the number of large
preantral follicles was not affected. In contrast, treatment with FSH increased
the number of small and large preantral follicles by 36 and 177% but did not
influence the number of primary and primordial follicles. Immunoblot analysis
showed an increase of CYP17, a theca cell marker, in the ovarian homogenate after
treatment with GDF-9 but not FSH. The present results indicate that in vivo
treatment with GDF-9 enhances the progression of primordial and primary follicles
into small preantral follicles. Thus, GDF-9 treatment could provide an
alternative approach to stimulate early follicle development in addition to the
widely used FSH that acts mainly on the development of more advanced follicles.
PMID- 11014239
TI - A novel messenger ribonucleic acid homologous to human MAGE-D is strongly
expressed in rat Sertoli cells and weakly in Leydig cells and is regulated by
follitropin, lutropin, and prolactin.
AB - We have cloned a novel complementary DNA whose expression was decreased in rat
Sertoli cell cultures after treatment with FSH. This complementary DNA encodes a
protein of 570 amino acids and shares 92% homology with the human MAGE-D protein.
In contrast to other MAGE genes (A, B, or C), we have shown that MAGE-D
expression was ubiquitous in healthy rat tissues. In the seminiferous tubules,
the MAGE-D was expressed in Sertoli cells but not in germ cells as demonstrated
by RT-PCR and in situ hybridization, whereas for the other MAGE genes, expression
has been shown to be restricted to germ cells. Interestingly, MAGE-D was also
detected for the first time in the female gonad by Northern blotting. In MLTC-1
cells (mouse Leydig tumor cell line-1), LH and PRL stimulated MAGE-D expression.
Using hypophysectomized rats, it was confirmed that FSH decreased MAGE-D
expression, whereas LH and PRL increased MAGE-D messenger RNA level in the whole
testis most probably through a direct action on Leydig cells. As MAGE-D is
present in both the seminiferous compartment and interstitium and hormonally
regulated in each, it is possible that it has specific functions in each
compartment during the development and the maintenance of the testis.
PMID- 11014240
TI - Functional connections between the suprachiasmatic nucleus and the thyroid gland
as revealed by lesioning and viral tracing techniques in the rat.
AB - Frequent blood sampling via intraatrial cannula revealed daily rhythms of TSH and
thyroid hormones in both male and female Wistar rats. Thermic ablation of the
biological clock, i.e. the suprachiasmatic nucleus (SCN), eliminated the diurnal
peak in circulating TSH and thyroid hormones. In addition, SCN lesions produced a
clear decrease of 24-h mean T4 concentrations. A more pronounced effect of SCN
lesions on thyroid hormones, as opposed to TSH, suggested routes of SCN control
additional to the neuroendocrine hypothalamopituitary-thyroid axis. Retrograde,
transneuronal virus tracing was used to identify the type and localization of
neurons in the central nervous system that control the autonomic innervation of
the thyroid gland. In the spinal cord and brain stem, both the sympathetic and
parasympathetic motorneurons were labeled. By varying the postinoculation
survival time, it was possible to follow the viral infection as it proceeded.
Subsequently, the pseudorabies virus (PRV) infected neurons in several brain stem
cell groups, the paraventricular nucleus of the hypothalamus (PVN) and the
central nucleus of the amygdala (second order labeling). Among PRV-infected
neurons in the PVN were TRH-containing cells. Third order neurons were found in
several hypothalamic cell groups, among which was the SCN. Therefore, we propose
that the SCN has a dual control mechanism for thyroid activity by affecting
neuroendocrine control of TSH release on the one hand and the autonomic input to
the thyroid gland on the other.
PMID- 11014241
TI - Estrogen receptors alpha and beta in rat decidua cells: cell-specific expression
and differential regulation by steroid hormones and prolactin.
AB - Estradiol is known to play an important role in the growth and differentiation of
rat uterine stromal cells into decidual cells. In particular, this hormone with
progesterone is necessary for blastocyst implantation and subsequent
decidualization in the rat. Although binding experiments have demonstrated the
presence of estrogen-binding sites, no evidence exists as to whether the rat
decidua expresses both isoforms of the estrogen receptor (ER), alpha and beta. In
this investigation, we analyzed the expression of decidual ERalpha and ERbeta,
studied their regulation by PRL and steroid hormones and examined the ability of
decidual ERp to transduce the estradiol signal to the progesterone receptor.
Immunocytochemistry, RT-PCR, and Northern blot analysis showed that both ER
species are coexpressed in the decidua during pseudopregnancy. Interestingly,
these genes were preferentially found in a cell population localized in the
antimesometrial site of the uterus where blastocyst implantation takes place.
Using decidual cells in primary culture obtained from pseudopregnant rats and a
decidua-derived cell line (GG-AD), we show a differential regulation of ERalpha
and ERbeta by PRL and ovarian steroid hormones. Whereas PRL, estradiol, and
progesterone all increased ERbeta messenger RNA (mRNA) expression in a dose
dependent manner, only PRL up-regulated the mRNA levels of ERa. Estradiol had no
effect on ERalpha expression, whereas progesterone markedly decreased its mRNA
levels. Interestingly, progesterone, which up-regulates the ability of PRL to
signal to a PRL-regulated gene in mammary-gland derived cells, prevented PRL
stimulation of decidual ERalpha and had no synergistic effect on ERbeta
expression. The use of GG-AD cells, which express only ERbeta, allowed us to
demonstrate that this receptor subtype is functional and transduces estradiol
signal to the progesterone receptor. In summary, the results of this
investigation have revealed that ERbeta is expressed in addition to ERalpha in
the rat decidua, and that the expression of both ERs are cell specific and
differentially regulated by PRL and steroids. One salient finding of this
investigation is that progesterone down-regulates ERalpha, but concomitantly
increases the expression of a functional ERbeta that mediates estradiol up
regulation of the decidual progesterone receptor.
PMID- 11014242
TI - In situ estrogen synthesized by aromatase P450 in uterine leiomyoma cells
promotes cell growth probably via an autocrine/intracrine mechanism.
AB - In the present study we characterized in detail the expression of aromatase P450
in leiomyomas to determine the role of in situ estrogen in the growth advantage
of leiomyomas. The levels of aromatase P450 transcripts were determined by
quantitative RT-PCR to be significantly higher in leiomyomas than in
corresponding myometrium. The overexpression of aromatase P450 in leiomyomas was
also confirmed by Western blot analysis. The estimated size of immunoreactive
aromatase was 58 kDa, similar to that in placenta. To identify a cell type that
express aromatase P450 in leiomyomas, histological specimens were stained for
aromatase P450 using a polyclonal antibody. Strong immunoreactivity was detected
in the cytoplasm of leiomyoma cells, whereas surrounding normal myometrium
displayed weak or negative staining. Smooth muscle-like cells in culture obtained
from leiomyomas, positive for actin D fiber, possessed immunoreactive granules of
aromatase in the cytoplasm. Conversion of androgen to estrogen was effectively
stimulated by phorbol myristate acetate and dexamethasone plus interleukin-1beta
and was completely abolished by selective inhibitors of aromatase P450 (fadrozole
and TZA-2209), but not by inhibitors of 5alpha-reductase (finasteride and
flutamide). The apparent Km of androstenedione was 3 nM in the presence of
dexamethasone and interleukin-1beta, corresponding to the plasma concentration of
androstenedione in women of reproductive age. To determine whether endogenous
aromatase P450 plays a role in the growth promotion of leiomyoma cells, we
evaluated the cell growth of smooth muscle-like cells treated with various
concentrations of estrogen and androgen using a WST-1 assay. Treatment with
testosterone (10(-8) and 10(-7) M) and androstenedione (10(-8) and 10(-7) M)
stimulated the growth of smooth muscle-like cells obtained from leiomyomas to the
same extent as estradiol (10(-10)-10(-7) M), whereas dihydrotestosterone (10(-11)
10(-8) M) did not. The stimulatory effect of testosterone on cell growth was
again abolished by cotreatment with fadrozole. The level of estradiol in the
medium of testosterone (10(-8) M)-treated smooth muscle-like cells was 10(-11) M,
which was 1 order lower than the minimum concentration of estradiol necessary to
promote cell growth (10(-10) M). This indicates that estradiol synthesized in
leiomyomas promotes their growth via an autocrine/intracrine mechanism. We
conclude that myometrial cells of leiomyomas overexpress aromatase P450 and are
able to synthesize sufficient estrogen to accelerate their own cell growth.
Overexpression of aromatase P450 may play a role in the growth advantage of
leiomyoma tissue over surrounding myometrium via an autocrine/intracrine
mechanism.
PMID- 11014243
TI - The role of D-aspartic acid and N-methyl-D-aspartic acid in the regulation of
prolactin release.
AB - In this study, using an enzymatic HPLC method in combination with D-aspartate
oxidase, we show that N-methyl-D-aspartate (NMDA) is present at nanomolar levels
in rat nervous system and endocrine glands as a natural compound, and it is
biosynthesized in vivo and in vitro. D-aspartate (D-Asp) is its natural precursor
and also occurs as an endogenous compound. Among the endocrine glands, the
highest quantities of D-Asp (78 +/- 12 nmol/g) and NMDA (8.4 +/- 1.2 nmol/g)
occur in the adenohypophysis, whereas the hypothalamus represents the area of the
nervous system where these amino acids are most abundant (55 +/- 9 and 5.6 +/-
1.1 nmol/g for D-Asp and NMDA, respectively). When D-Asp is administered to rats
by ip injection, there is a significant uptake of D-Asp into the adenohypophysis
and a significant increase in the concentration of NMDA in the adenohypophysis,
hypothalamus and hippocampus, suggesting that D-Asp is an endogenous precursor
for NMDA biosynthesis. Experiments conducted on tissue homogenates confirm that D
Asp is the precursor of the NMDA and that the enzyme catalyzing this reaction is
a methyltransferase. S-adenosyl-L-methionine (SAM) is the methyl group donor. In
vivo experiments consisting of ip injections of sodium D-aspartate show that this
amino acid induced a significant serum PRL elevation and this effect is dose and
time dependent. In vitro experiments conducted on isolated adenohypophysis or
adenohypophysis coincubated with the hypothalamus, showed that the release of PRL
is caused by a direct action of D-Asp on the pituitary gland and also mediated by
the indirect action of NMDA on the hypothalamus. Then, the latter induces the
release of a putative factor that in turn stimulates the adenohypophysis
reinforcing the PRL release. In conclusion, our data suggest that D-Asp and NMDA
are present endogenously in the rat and are involved in the modulation of PRL
release.
PMID- 11014244
TI - Aldosterone: a mediator of myocardial necrosis and renal arteriopathy.
AB - To determine the role of aldosterone in mediating cardiovascular damage, we
performed ablation/replacement experiments with aldosterone in a rat model of
cardiac injury. Administration of angiotensin II and Nomega-nitro-L-arginine
methyl ester (L-NAME; nitric oxide synthesis inhibitor) to male rats drinking 1%
saline caused hypertension, severe biventricular myocardial necrosis,
proteinuria, and fibrinoid necrosis of renal and cardiac vessels. Removal of
aldosterone by adrenalectomy or through administration of the selective
aldosterone antagonist eplerenone markedly reduced the cardiac and renal damage
without significantly altering blood pressure. Aldosterone infusion in
adrenalectomized, glucocorticoid-replaced L-NAME/angiotensin II-treated animals
restored damage. Thus, we identified aldosterone as a critical mediator of L
NAME/angiotensin II induced vascular damage through mechanisms apparently
independent of its effects on systolic blood pressure.
PMID- 11014245
TI - Growth hormone increases connexin-43 expression in the cerebral cortex and
hypothalamus.
AB - Several studies indicate that systemic GH influences various brain functions.
Connexin-43 forms gap junctions that mediate intercellular communication and
establish the astroglial syncytium. We investigated the effects of peripheral
administration of bovine GH (bGH) and recombinant human insulin-like growth
factor I (rhIGF-I) on the expression of connexin-43 in the rat brain.
Hypophysectomized female Sprague Dawley rats were substituted with cortisol (400
microg/kg x day) and L-T4 (10 microg/kg x day) and treated with either bGH (1
mg/kg x day) or rhIGF-I (0.85 mg/kg x day) for 19 days. The abundance of connexin
43 messenger RNA (mRNA) and protein in the brainstem, cerebral cortex,
hippocampus, and hypothalamus was quantified by means of ribonuclease protection
assays and Western blots. Treatment with bGH increased the amounts of connexin-43
mRNA and protein in the cerebral cortex and hypothalamus. No changes were found
in the brainstem or hippocampus. Infusion of rhIGF-I did not affect connexin-43
mRNA or protein levels in any of the brain regions studied. These results show
that administration of bGH increases the abundance of cx43 in specific brain
regions, suggesting that GH may influence gap junction formation and thereby
intercellular communication in the brain.
PMID- 11014246
TI - Thyroid hormone acts directly on growth plate chondrocytes to promote
hypertrophic differentiation and inhibit clonal expansion and cell proliferation.
AB - T3 is an important regulator of endochondral bone formation in epiphyseal growth
plates. Growth arrest in juvenile hypothyroidism results from disorganization of
growth plate chondrocytes and their failure to undergo hypertrophic
differentiation, but it is unclear how T3 acts directly on chondrocytes or
whether its actions involve other pathways. To address this issue, we
investigated whether thyroid hormone receptors (TR) were localized to discrete
regions of the unfused epiphysis by immunohistochemistry performed in tibial
growth plates from 21-day-old rats and examined the effects of T3 on growth plate
chondrocytes in agarose suspension cultures in vitro. TRalpha1, -alpha2, and
beta1 were expressed in reserve and proliferating zone chondrocytes, but not in
hypertrophic cells, suggesting that progenitor cells and immature chondrocytes
are the major T3 target cells in the growth plate. Chondrocytes in suspension
culture expressed TRalpha1, -alpha2, and -beta1 messenger RNAs and matured by an
ordered process of clonal expansion, colony formation, and terminal hypertrophic
differentiation. Clonal expansion and proliferation of chondrocytes were
inhibited by T3, which also induced alkaline phosphatase activity, expression of
collagen X messenger RNA, and secretion of an alcian blue-positive matrix as
early as 7 days after hormone stimulation. Thus, T3 inhibited chondrocyte clonal
expansion and cell proliferation while simultaneously promoting hypertrophic
chondrocyte differentiation. These data indicate that thyroid hormones
concurrently and reciprocally regulate chondrocyte cell growth and
differentiation in the endochondral growth plate.
PMID- 11014247
TI - Comparative effects of neonatal exposure of male rats to potent and weak
(environmental) estrogens on spermatogenesis at puberty and the relationship to
adult testis size and fertility: evidence for stimulatory effects of low estrogen
levels.
AB - This study investigated whether neonatal exposure of male rats to estrogenic
compounds altered pubertal spermatogenesis (days 18 and 25) and whether the
changes observed resulted in long-term changes in testis size, mating, or
fertility (days 90-100). Rats were treated neonatally with a range of doses (0.01
10 microg) of diethylstilbestrol (DES; administered on alternate days from days 2
12), a high dose of octylphenol (OP; 2 mg administered daily from days 2-12) or
bisphenol A (Bis-A; 0.5 mg administered daily from days 2-12), or vehicle, while
maintained on a standard soy-containing diet. The effect on the same parameters
of rearing control animals on a soy-free diet was also assessed as was the effect
of administering such animals genistein (4 mg/kg/day daily from days 2-18).
Testis weight, seminiferous tubule lumen formation, the germ cell apoptotic index
(apoptotic/viable germ cell nuclear volume), and spermatocyte nuclear volume per
unit Sertoli cell nuclear volume were used to characterize pubertal
spermatogenesis. Compared with (soy-fed) controls, DES administration caused dose
dependent retardation of pubertal spermatogenesis on day 18, as evidenced by
decreases in testis weight, lumen formation, and spermatocyte nuclear volume per
unit Sertoli cell and elevation of the germ cell apoptotic index. However, the
two lowest doses of DES (0.1 and 0.01 microg) significantly increased
spermatocyte nuclear volume per unit Sertoli cell. Similarly, treatment with
either OP or Bis-A significantly advanced this and some of the other aspects of
pubertal spermatogenesis. Maintenance of control animals on a soy-free diet also
significantly advanced lumen formation and spermatocyte nuclear volume per unit
Sertoli cell compared with controls fed a soy-containing diet. Administration of
genistein reversed the stimulatory effects of a soy-free diet and significantly
retarded most measures of pubertal spermatogenesis. In general, plasma FSH levels
in the treatment groups changed in parallel to the spermatogenic changes (reduced
when pubertal spermatogenesis retarded, increased when pubertal spermatogenesis
advanced). By day 25, although the changes in FSH levels largely persisted, all
of the stimulatory effects on spermatogenesis seen on day 18 in the various
treatment groups were no longer evident. In adulthood, testis weight was
decreased dose dependently in rats treated neonatally with DES, but only the
lowest dose group (0.01 microg) showed evidence of mating (3 of 6) and normal
fertility (3 litters). Animals treated neonatally with OP or Bis-A had normal or
increased (Bis-A) testis weights and exhibited reasonably normal
mating/fertility. Animals fed a soy-free diet had significantly larger testes
than controls fed a soy-containing diet, and this difference was confirmed in a
much larger study of more than 24 litters, which also showed a significant
decrease in plasma FSH levels and a significant increase in body weight in the
males kept on a soy-free diet. Neonatal treatment with genistein did not alter
adult testis weight, and although most males exhibited normal mating and
fertility, a minority did not mate or were infertile. It is concluded that 1)
neonatal exposure of rats to low levels of estrogens can advance the first wave
of spermatogenesis at puberty, although it is unclear whether this is due to
direct effects of the estrogen or to associated elevation of FSH levels; 2) the
effect of high doses of OP and Bis-A on these processes is essentially benign;
and 3) the presence or absence of soy or genistein in the diet has significant
short-term (pubertal spermatogenesis) and long-term (body weight, testis size,
FSH levels, and possibly mating) effects on males.
PMID- 11014248
TI - 17beta-estradiol, but not raloxifene, decreases thrombomodulin in the
antithrombotic protein C pathway.
AB - Raloxifene is a nonsteroidal selective estrogen receptor modulator (SERM) that
mimics the effects of estrogen on some plasma lipids and may have direct effects
on the vascular wall. The objective of this study was to determine the effects of
17beta-estradiol, raloxifene, and LY139,478 (a related benzothiophene SERM) on
the anticoagulant protein C pathway. In human vascular endothelial cells
activated with interleukin-1 (IL-1), we demonstrated decreased thrombomodulin
dependent protein C activation. 17beta-estradiol reduced the anticoagulant
properties of both unstimulated and IL-1-activated endothelial cells by
decreasing thrombomodulin expression. In contrast, raloxifene and LY139,478
enhanced the anticoagulant properties of both unstimulated and IL-1-activated
endothelial cells through upregulation of thrombomodulin. Regulation of the
protein C pathway via thrombomodulin on vascular endothelium may be a novel
mechanism by which SERMs could potentially confer cardioprotective effects and
reduce the thrombotic risk associated with HRT in compromised patients.
PMID- 11014249
TI - Estrogen agonist and antagonist action on the human estrogen receptor in
Drosophila.
AB - The estrogen receptor (ER) regulates the expression of genes involved in the
growth, proliferation and differentiation of skeletal, cardiovascular, neural and
reproductive tissues. A basic scheme for the mechanism for ER action has been
developed, but precise details on the interactions between ER and the cellular
signaling and transcription machinery required for receptor-mediated regulation
of specific target genes are still lacking. We have developed a genetic approach
to explore the functional interactions of ER. In this work, we describe the
development of an estrogen responsive system in the fruit fly, Drosophila
melanogaster. Transgenic flies carrying the human ER alpha and an estrogen
responsive green fluorescent protein (GFP) reporter gene were constructed. In
vivo expression of the GFP reporter gene was observed when larvae were grown on a
food source containing steroidal or nonsteroidal estrogens. The induction of the
reporter gene by estrogens was blocked upon treatment with tamoxifen, an estrogen
antagonist. However, we failed to recapitulate ligand-independent activation of
the receptor in vivo or in cultured Drosophila cells. An estrogen responsive
Drosophila system could be used to identify and characterize the complex
functional interactions between ER and the other components of the cellular
transcriptional apparatus.
PMID- 11014251
TI - The evolving role of sonography in evaluating solid breast masses.
AB - Many investigators have attempted to use ultrasound imaging to differentiate
benign from malignant solid breast masses. Studies have evaluated several
generations of gray-scale imaging, Doppler, color Doppler, and power Doppler
imaging, and several unconventional ultrasound techniques. Although various
individual studies have shown promise, ultrasound criteria for avoiding biopsy of
solid lesions have not been widely adopted. Considerable observer variability
also remains an important obstacle. This article reviews the results, strengths,
and weaknesses of some of the key studies addressing this issue. Fundamental
criteria for a successful ultrasound model are also specified.
PMID- 11014252
TI - Use of Doppler ultrasound in the evaluation of breast carcinoma.
AB - Ultrasound is an imaging modality commonly used to evaluate breast lesions in
hopes to distinguish benign from malignant solid masses. Angiogenesis, defined as
the emergence of new vessels to further the growth of tumor, has stimulated
interest in the potential uses of Doppler ultrasound in patients with breast
cancer. This article describes different forms of Doppler ultrasound, including
color Doppler (CD), power Doppler (PD), and spectral Doppler (SD), as well as 3
dimensional (3D) ultrasound and ultrasound contrast media. We review the role of
Doppler ultrasound in distinguishing benign from malignant solid breast masses.
We also discuss the role of ultrasound in predicting tumor grade, histology, node
status, and lymphatic vascular invasion, and in monitoring breast cancer
treatment.
PMID- 11014250
TI - Is the early increase in leptinemia one of the anorectic signals induced by an
essential amino acid-deficient diet in the rat?
AB - Rats start decreasing their food intake as early as 70 min after the first
ingestion of a food deficient in threonine. A decrease of the limiting essential
amino acid (EAA) in the plasma was proposed to be the first anorectic signal.
Because many hormones regulate feeding behavior, we studied the effect of a meal
(46 kJ) that was either devoid of threonine or was corrected for the deficiency,
on plasma leptin, insulin and glucagon levels using a radio-immunoassay, at 0 to
180 min after the meal. One hour after ingestion of the threonine-devoid meal, a
larger increase in insulinemia (22+/-1 vs. 15+/-1 microU/ml) and leptinemia
(7.8+/-0.5 vs. 4.4+/-0.6 ng/ml; p<0.001) was observed than after ingestion of the
corrected meal. The area under the curve of the threonine-devoid meal group was 3
and 1.34 fold larger than for the corrected meal group for insulin and leptin
respectively. Glucagonemia was not different between the two groups. We propose
that the rise in leptinemia, perhaps in synergy with rise in plasma insulin,
might serve as one early signal to brain structures, participating in the
anorectic mechanism following ingestion of an EAA-deficient diet.
PMID- 11014253
TI - Texture analysis of breast tumors on sonograms.
AB - We performed a feasibility study to determine if the texture features extracted
from sonograms can be used to predict malignant or benign breast pathology by the
proposed artificial neural network and to compare the diagnostic results with the
radiologists' results. A total of 1,020 images (4 different rectangular regions
from the 2 orthogonal imaging planes of each tumor) from 255 patients were used
as samples. When a sonogram was performed, 1 physician identified the region of
interest in the sonogram; then, a neural network model, using 24 autocorrelation
texture features, classified the tumor as benign or malignant. Three radiologists
who were unfamiliar with the samples also classified these images. The receiver
operating characteristic (ROC) area index for the proposed neural network system
is 0.9840 +/- 0.0072. The neural network identified 35 of 36 malignancies and 211
of 219 benign tumors using all 4 regions of interest. The radiologists, on
average, identified 19 of 36 malignancies, with 12 tumors called indeterminate
and 4 tumors called benign. We conclude that benign and malignant breast tumors
can be distinguished using interpixel correlation in digital ultrasonic images.
PMID- 11014254
TI - The role of ultrasound in the diagnosis of breast cancer.
AB - Ultrasonography (US) of the breast is not applied to its optimal capacity if it
is restricted to the differentiation between cystic and solid lesions and
evaluation of dense breasts. It can play a major role in the detection of breast
cancer; not only because of detection of mammographically occult lesions but also
because of more accurate identification of lesion characteristics suspicious of
malignancy. Its yield is highest among women younger than 50 years. However, one
should keep in mind that the profit obtained by US shows not only the diagnostic
accuracy of US but also that of mammography. Further improvement can be achieved
by refinement in US diagnosis, especially with respect to the US characteristics
of diffusely growing cancers.
PMID- 11014255
TI - Clinically and mammographically occult breast lesions: detection and
classification with high-resolution sonography.
AB - With recent significant advances in ultrasound technology, the potential of high
resolution sonography to improve the sensitivity of cancer diagnosis in women
with dense breasts has become a matter of interest for breast imagers. To
determine how often physician-performed high-resolution sonography can detect
nonpalpable breast cancers that are not revealed by mammography, 8,970 women with
breast density grades 2 through 4 underwent high-resolution sonography as an
adjunct to mammography. All sonographically detected, clinically and
mammographically occult breast lesions that were not simple cysts were
prospectively classified into benign, indeterminate, or malignant categories.
Diagnoses were confirmed by ultrasound-guided fine-needle aspiration, core-needle
biopsy, or surgical biopsy. In 8,103 women with normal findings at mammography
and physical examination, 32 cancers and 330 benign lesions were detected in 273
patients with sonography only. Eight additional cancers were found in 867
patients with a malignant (n = 5) or a benign (n = 3) palpable or
mammographically detected index lesion. The overall prevalence of cancers
detected with screening sonography was 0.41%, and the proportion of
sonographically detected cancers to the total number of nonpalpable cancers was
22%. The mean size of invasive cancers detected only by sonography was 9.1 mm,
and was not statistically different from the mean size of invasive cancers
detected by mammography. The sensitivity of prospective sonographic
classification for malignancy was 100%, and the specificity was 31%. In
conclusion, the use of high-resolution sonography as an adjunct to mammography in
women with dense breasts may lead to detection of a significant number of
otherwise occult cancers that are no different in size from nonpalpable
mammographically detected cancers. Prospective classification of these lesions
based on sonographic characteristics resulted in an acceptable benign-to
malignant biopsy rate of 6.3:1.
PMID- 11014256
TI - Insecticidal rocaglamide derivatives from Aglaia spectabilis (Meliaceae).
AB - Bark of Aglaia spectabilis collected on the island of Phu Quoc (Vietnam) yielded
insecticidal cyclopentatetrahydrobenzofurans of the rocaglamide type including
four new natural products. Structure elucidation of the new compounds is
described. All rocaglamide derivatives isolated exhibited strong insecticidal
activity towards neonate larvae of the polyphagous pest insect Spodoptera
littoralis when incorporated into an artificial diet. LC50 values varied from 0.8
to 80 ppm. The most active compounds isolated, methylrocaglate and C-3'
hydroxylmethylrocaglate, were similar with regard to their insecticidal activity
to the well-known natural insecticide azadirachtin.
PMID- 11014257
TI - A geranylated chalcone with 5alpha-reductase inhibitory properties from
Artocarpus incisus.
AB - A geranylated chalcone was isolated from leaves of Artocarpus incisus and it
showed potent 5alpha-reductase inhibitory activity.
PMID- 11014258
TI - Saikosaponins from roots of Bupleurum gibraltaricum and Bupleurum spinosum.
AB - Two new saikosaponins have been identified in the butanolic fraction of the
ethanol extract of the roots of Bupleurum spinosum: 3beta,16alpha,23,28
tetrahydroxyoleana-11,13(18)-dien- 30-oic acid 3-O-beta-D-glucopyranosyl-(1 -->
2)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-fucopyranoside, and
3beta,16alpha,23,28,30-pentahydroxyoleana-11,13(18)-diene 3-O-beta-D
glucopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-fucopyranoside.
3Beta,16beta,23-trihydroxy-13,28-epoxyolean-11-ene 3-O-beta-D-glucopyranosyl-(1 -
> 2)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-fucopyranoside was also isolated, and
this structure agreed with the one proposed for bupleuroside I, but their
spectroscopic data have not been described until now. From the same fraction of
the roots of Bupleurum gibraltaricum, the known compound buddlejasaponin IV has
been isolated as the predominant component (90%). Structures were elucidated
using spectroscopic analysis, specially 2D-NMR experiments.
PMID- 11014259
TI - Volatile constituents of wood-rotting basidiomycetes.
AB - Phytochemical investigation of the hydrodistillation products of the
basidiomycetes Fomitopsis pinicola, Piptoporus betulinus, Gloeophyllum odoratum
and Trametes suaveolens led to the identification of numerous mono- and
sesquiterpenes as well as many aliphatic alcohols, aldehydes and ketones and some
aromatic compounds. In addition, some diterpenes were identified as constituents
of Fomitopsis pinicola. The absolute configuration of some terpenes was
determined
PMID- 11014261
TI - Constituents of the fungi Daedalea quercina and Daedaleopsis confragosa var.
tricolor.
AB - Phytochemical examination of solvent extracts of the wood-rotting fungi Daedalea
quercina and Daedaleopsis confragosa var. tricolor led to the isolation of five
new triterpene derivatives and some known fungal constituents. All structures
were identified by one- and two-dimensional NMR spectroscopy and mass
spectrometry. From Daedalea quercina, the new natural products 16-O
acetylpolyporenic acid C, 16alpha-acetoxy-24-methylene-3-oxolanost-8-en-21-oic
acid, (+)-24-methylene-3,23-dioxolanost-8-en-26-oic acid, (+)-3beta,12beta
dihydroxy-24-methyl-23-oxolanost-8-en-26-oi c acid and 12beta,23-epoxy-3alpha,23
dihydroxy-24-methyllanost-8- en-26-oic acid could be isolated. From Daedaleopsis
confragosa var. tricolor, the compounds 3alpha-carboxyacetoxyquercinic acid,
3alpha-carboxyacetoxy-24-methylene-23-oxolanost-8-en-2 6-oic acid and
5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol were identified. These are the
first described triterpene derivatives isolated from this fungus.
PMID- 11014260
TI - Triterpene saponins and iridoid glucosides from galium rivale.
AB - Three new glycosides of the oleanene-type triterpenes, rivalosides C-E (1-3),
along with three known triterpene saponins, momordin IIb (4) and rivalosides A-B
(5-6), and five known iridoid glucosides: monotropein, scandoside,
deacetylasperulosidic acid, geniposidic acid and asperulosidic acid, were
isolated from aerial parts of Galium rivale. The structures of the new compounds
were elucidated by spectral methods and chemical means as 2alpha-acetoxy-3alpha,
19alpha-dihydroxy-olean-12-en-28-oic acid 28-O-beta-D-glucopyranosyl-(1--> 6)
beta-D-glucopyranoside, 2alpha,3alpha, 19alpha-trihydroxy-olean- 12-en-28-oic
acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside and 3-O-beta-D
glucuronopyranosyl-24-hydroxy-olean-12-en-28-oic acid 28-O-beta-D
glucopyranoside, for rivalosides C-E, respectively. The taxonomic significance of
the rivalosides in G. rivale was discussed.
PMID- 11014262
TI - Sesquiterpenoids and phenolics from Crepis mollis.
AB - From the roots of Crepis mollis, one new and two known guaianolides were isolated
together with eight known guaianolide glycosides, one known germacranolide
glycoside and two known phenylpropanoids. The structure and relative
configuration of the new compound were established as 9alpha-hydroxy-4beta, 15,
11beta, 13-tetrahydro-dehydrozaluzanin C by spectral methods.
PMID- 11014263
TI - Diterpenoids from the roots of Croton macrostachys.
AB - Three novel diterpenoids have been isolated from the roots of Croton
macrostachys. The structure and stereochemistry of the compounds have been
unambiguously settled as neoclerodan-5,10-en-19,6beta;20,12-diolide, 3alpha, 19
dihydroxytrachylobane, and 3alpha,18,19-trihydroxytrachylobane from detailed
spectroscopic evidence.
PMID- 11014264
TI - Labdane diterpenes from Otostegia fruticosa.
AB - The new labdane diterpenes otostegin A (2), otostegin B (6) and 15-epi-otostegin
B (7) were isolated from the aerial parts of Otostegia. fruticosa, besides the
previously known labdanes preleoheterin (1), leoheterin (3), leopersin C and 15
epi-leopersin C (4, 5), ballonigrin (9) and vulgarol (11), along with the iridoid
glucoside 8-O-acetylharpagide (10). The structure elucidation of all the isolated
compounds was based on their spectral data and chemical derivatization.
PMID- 11014265
TI - Highly oxidized cuparene-type sesquiterpenes from a mycelial culture of
Flammulina velutipes.
AB - Cuparene-type sesquiterpenes were isolated from a culture broth of Flammulina
velutipes (Curt.:Fr.) Sing. Using spectroscopic methods (HR-MS, 1H and 13C NMR,
and 2D NMR, spectroscopy), their structures were determined to be 2,3,4,5
tetrahydro-2,7-dihydroxy-5,8,10,10-tetramethyl-2,5-methano-1- benzoxepin and 5
methyl-2-(3-oxo-1,2,2-trimethylcyclopentyl)benzoquinone. Both showed
antimicrobial activity against Cladosporium herharum and Bacillus subtilis.
PMID- 11014266
TI - Minor sulfated saikosaponins from the aerial parts of Bupleurum rigidum L.
AB - Five new sulfated saikosaponins (Sandrosaponins II-VI) were isolated as minor
components from the aerial parts of Bupleurum rigidum L. Their structures have
been established by 1D and 2D-NMR techniques, FABMS, and chemical methods. ,
PMID- 11014267
TI - Sesquiterpenoids from roots of Taraxacum laevigatum and Taraxacum disseminatum.
AB - Chromatographic separation of ethanolic root extracts of Taraxacum laevigatum and
Taraxacum disseminatum afforded a total of eight germacrane- and eudesmane-type
sesquiterpenoids. including new compounds, 1beta,3beta,6alpha-trihydroxy-4alpha(
15)-dihydrocostic acid methyl ester and its 1-O-beta-glucopyranoside. Their
structures were established by spectroscopic analyses. In addition, the structure
of 4alpha(15), 11beta(13)-tetrahydroridentin B-1-O-beta-glucopyranoside was
elucidated by extensive NMR studies.
PMID- 11014269
TI - Tirucallane triterpenoids from Dysoxylum hainanense.
AB - Four tirucallane derivatives, 3beta,22S-dihydroxy-tirucalla-7,24-dien-23-one,
22,23-epoxy-tirucalla-7-ene-3beta,24,25-triol, 3beta,25-dihydroxy-tirucalla-7,23
diene, 23,26-dihydroxy-tirucalla-7,24-dien-3-one, together with two known
triterpenoids, 24,25-epoxy-3beta,23-dihydroxy-7-tirucallene, tirucalla-7,24-diene
3beta,23-diol, were isolated from Dysoxylum hainanense. Their structures were
elucidated on the basis of spectroscopic evidence.
PMID- 11014268
TI - Saponins from Lonicera bournei.
AB - The lupane-triterpene glycosides, bourneioside A and bourneioside B, and two
known saponins were isolated from Lonicera bournei Hemsl. The structures of
bourneioside A and B were elucidated as 3-O-beta-D-glucopyranosyl-23-hydroxy-lup
20(29)-en-28-oic acid-28-O-beta-D-glucopyranosyl ester and 3-O-beta-D
glucopyranosyl-23-hydroxy-lup-20(29)-en-28-oic acid-28-O-[beta-D-glucopyranosyl
(1 --> 6)-beta-D-glucopyranosyl] ester, respectively, on the basis of spectral
data and chemical evidence.
PMID- 11014270
TI - Iridoids from Caryopteris x clandonensis.
AB - In continuation of our phytochemical studies on Caryopteris x clandonensis
(Lamiaceae), three further iridoids were isolated from the methanolic extract of
the stems. Their structures were established by 1D and 2D NMR and MS analysis as
a C-6 epimer of 8-O-acetylharpagide (6-epi-8-O-acetylharpagide), a derivative of
harpagide which contained the unusual feature of a 3',4' seco-glycopyranosyl
moiety (clandonoside II) and a methyl cetal of 8-O-acetylharpagide aglucone
hydrate named clandonensine.
PMID- 11014271
TI - Sesquiterpene lactone and friedelane derivative from drypetes molunduana.
AB - A new sesquiterpene lactone, drypemolundein A and a new friedelane derivative,
drypemolundein B, along with seven known compounds have been isolated from the
whole stems of Drypetes molunduana Pax and Hoffm. Their structures were
established on the basis of one- and two-dimensional NMR, homo- and hetero
nuclear spectroscopic evidence.
PMID- 11014272
TI - Triterpenoid saponins from Ardisia mamillata.
AB - Two saponins were isolated from the roots of Ardisia mamillata HANCE. Their
structures were established on the basis of MALDI-TOFMS, 1H, 13C NMR and 2D NMR
(COSY, HOHAHA, HETCOR, HMBC and ROESY) spectra, and on chemical evidence, to be
ardisimamilloside A, 3-O-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl
(1 --> 4)-[beta-D-glucopyranosyl-(1 --> 2)]-alpha-L-arabinopyranosyl]-3beta,
16alpha,28alpha-trihydroxy-13beta,28-epoxy-oleanan+ ++-30-al; and
ardisimamilloside B, 3-O-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl
(1 --> 4)-[beta-D-glucopyranosyl-( 1 --> 2)]-alpha-L-arabinopyranosyl]-beta3
hydroxy-13beta,28- epoxy-oleanan-16-oxo-30-al.
PMID- 11014273
TI - Two oleanane triterpenoids from gordonia ceylanica and their conversions to
taraxarane triterpenoids.
AB - Chemical investigation of the hot hexane extract of the stem bark of Gordonia
ceylanica afforded two new oleanane triterpenoids, 3beta-acetoxy-11alpha, 13beta
dihydroxyolean-12-one and 3beta,11alpha-diacetoxy-13beta-hydroxyolean-12-one (2)
The attempted acid hydrolysis of these two compounds resulted the dehydration and
subsequent methyl group migration to afford the taraxarane triterpenoids
3beta,11alpha-dihydroxytaraxer-14-en-12-one (4) and 3beta-hydroxy-11alpha
acetoxytaraxer-14-en-12-one (5), respectively. These taraxaranes have not been
previously reported.
PMID- 11014274
TI - Taxane diterpenoids from Taxus yunnanensis and Taxus cuspidata.
AB - Chemical examination of the seeds of the Chinese yew, Taxus runnanensis Cheng et
L. K. Fu and the Japanese yew, Taxus cuspidata Sieb et Zucc, resulted in the
isolation of four taxane diterpenoids. The structures of these taxoids were
established as (12alpha)-2alpha-acetoxy-5alpha,9alpha, 10beta-trihydroxy-3,11
cyclotax-4(20)-en-13-one; 2alpha,7beta,13alpha-triacetoxy-5alpha, 9alpha
dihydroxy-2(3-->20)abeotaxa-4(20),11-dien-10-one; 9alpha,10beta-diacetoxy-5alpha
cinnamoyloxytaxa- 4(20),11-dien-13alpha-ol and the known
2alpha,7beta,9alpha,10beta,13-pentaacetoxytax a-4(20),12-diene-5alpha,11beta-diol
on the basis of spectral analysis.
PMID- 11014275
TI - Euphane triterpenoid and lipid constituents from Butea monosperma.
AB - Besides stigmasterol, stigmasterol-betaD-glucopyranoside and nonacosanoic acid,
two new compounds isolated from the stems of Butea monosperma have been
characterised as 3alpha-hydroxyeuph-25-ene and 2,14-dihydroxy-11,12-dimethyl-8
oxo-octadec-11-enylcyclohexane+ ++ by spectral data and chemical studies.
PMID- 11014276
TI - Neutral taxoids from Taxus cuspidata as modulators of multidrug-resistant tumor
cells.
AB - Two taxoids, taxinine NN-7 (1) and 3,11-cyclotaxinine NN-2 (2), were isolated
from the neutral fraction of the EtOAc extract of a mixture of needles and young
stems of Taxus cuspidata. The structures were determined by spectroscopic
analysis. Both compounds showed some activity as modulators of multidrug
resistant tumor cells.
PMID- 11014277
TI - Diterpene glucosides from Pieris formosa.
AB - Five diterpene glucosides, pierisformosides B-F were isolated from Pieris formosa
D. Don (Ericaceae). Their structures were elucidated on the basis of spectral
analysis. including 1H-1H COSY, 13C-1H COSY, HMBC and NOESY experiments.
PMID- 11014278
TI - Triterpenoid saponins from Fagonia cretica.
AB - Four new triterpenoid saponins were isolated and identified from the aerial parts
of Fagonia cretica. They were characterized as 3-O-[beta-D-glucopyranosyl (1-->2)
alpha-L-arabinopyranosyl] hederagenin 28-O-beta-D-glucopyranosyl ester, 3-O-[beta
D-glucopyranosyl (1-->2)-alpha-L-arabinopyranosyl] oleanolic acid 28-O-[beta-D
glucopyranosyl (1-->6)-beta-D-glucopyranosyl] ester, 3-O-[beta-D-glucopyranosyl
(1-->2)-alpha-L-arabinopyranosyl] 27-hydroxy oleanolic acid 28-O-[beta-D
glucopyranosyl (1-->6)-beta-D-glucopyranosyl] ester and 3beta-O-[beta-D
glucopyranosyl (1-->2)-alpha-L-arabinopyranosyl] olean-12-en-27-al-28-oic acid 28
O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] ester. The structures of
the saponins were assigned by spectral analyses (FABMS, 1H, 13C NMR, 1H-1H COSY,
TOCSY, HMQC and HMBC spectra) and NOE experiments. To the best of our knowledge
the genin 3beta hydroxy olean-12-en-27-al-28-oic acid is new.
PMID- 11014279
TI - Triterpenoidal constituents from Eucalyptus camaldulensis var. obtusa leaves.
AB - An investigation on the constituents of the fresh, uncrushed leaves of Ecalyptus
camaldulensis var. obtusa has led to the isolation of the triterpenoid amirinic
acid and four known triterpenoids ursolic acid lactone, betulinic acid, oleanolic
acid and ursolic acid. Amirinic acid transformed into amirolide in deuterated
chloroform at room temperature. The new products were characterized by exhaustive
spectroscopic studies as 2alpha,3beta,7beta-trihydroxy-11alpha-methoxyurs -12-en
28-oic acid and 2alpha,3beta,7beta-trihydroxyurs-11-en-28,13beta -olide.
PMID- 11014280
TI - Prieurianoside, a protolimonoid glucoside from the leaves of Trichilia
prieuriana.
AB - The ubiquitous glycolipid 1,2-dilinolenoyl-3-galactopyranosylglycerol and a new
protolimonoid glucoside, named prieurianoside, were isolated from the leaves of
Trichilia prieuriana. The structure of the latter was established, by
spectroscopic techniques, as 12beta,21-diacetoxy-29-beta-D-glucopyranosyloxy
23zeta -hydroxytirucalla-7,24-dien-3-one.
PMID- 11014281
TI - A stilbene and dihydrochalcones with radical scavenging activities from
Loiseleuria procumbens.
AB - A new dihydrochalcone, 6''-acetylphloridzosid, was isolated from the whole plant
of Loiseleuria procumbens (L.) Desv. and identified as 2'-O-(6''-O
acetylglucopyranosyl)-4,4',6'-trihydroxydihydrochal cone by spectroscopic
methods. In addition, one stilbene and three other dihydrochalcones were
identified as (E)-piceid, phloretin (2',4,4',6'-tetrahydroxydihydrochalcone),
phloridzosid (2'-O-glucopyranosyl-4,4',6'-trihydroxydihydrochalcone) and asebotin
(2'-O-glucopyranosyl-4'-methoxy-4,6'-dihydroxydihydrochalcone), respectively.
Some of these compounds showed scavenging properties towards the 2,2-diphenyl-1
picrylhydrazyl radical and antioxidant properties in a test with lysozyme.
PMID- 11014282
TI - Stilbene dimers from the lianas of Gnetum hainanense.
AB - Five stilbene dimers, gnetuhainins F-J, were isolated together with gnetulin,
rhapontigenin, isorhapontigenin and gnetol from the lianas of Gnetum hainanense
C. Y. Cheng. Their structures and stereochemistry have been established on the
basis of spectral evidence, especially 2D NMR spectroscopic techniques.
PMID- 11014283
TI - Benzophenone glycosides from Gnidia involucrata.
AB - Six compounds have been isolated from the methanol extract of the aerial parts of
Gnidia involucrata (Thymelaeaceae). They were identified as 2,3,4',5,6
pentahydroxybenzophenone-4-C-glucoside and 2,4',6-trihydroxy-4
methoxybenzophenone-2-O-glucoside, together with mangiferin, kaempferol-3-O
glucoside, yuankanin and manniflavanone by chemical and spectroscopic means. The
structures of three additional C-glycosyl flavones--vitexin, isovitexin and
isoorientin--were determined on-line by LC/UV/APCI-MSn analysis of the crude
extract.
PMID- 11014284
TI - Minor phenolics from Crinum bulbispermum bulbs.
AB - From the bulbs of Crinum bulbispermum Milne, four new minor compounds were
isolated viz. 4-hydroxy-2',4'-dimethoxydihydrochalcone (1), 4,5-methylenedioxy-4'
hydroxy-2-aldehyde[1,1'-biphenyl] (4), hippacine (6), and 4'-hydroxy-7
methoxyflavan-3-ol (7). In addition, four known compounds were isolated and
identified as 2(S),3',4'-dihydroxy-7-methoxy flavan (2), isolarrien (3),
isoliquiritigenin (5) and liquiritigenin (8). The structures of the isolated
compounds were established by spectral evidence.
PMID- 11014285
TI - Spectral comparisons of coniferyl and cinnamyl alcohol epoxide derivatives with a
purported cis-epoxyconiferyl alcohol isolate.
AB - The reported isolation of cis-epoxyconiferyl alcohol must be incorrect, based
upon comparison of the reported Nuclear Magnetic Resonance (NMR) spectral data
for the isolate with those for synthesized coniferyl and cinnamyl alcohol epoxide
derivatives. Attempts to prepare cis- and trans-coniferyl alcohols were
unsuccessful, although their acetate derivatives could be synthesized. The NMR
spectral data for a synthetic sample of pinoresinol were in excellent agreement
with those for the purported isolate.
PMID- 11014286
TI - Dihydroflavonols from Lannea coromandelica.
AB - The dihydroflavonols, (2R,3S)-(+)-3',5-dihydroxy-4',7-dimethoxydihydroflavonol
and (2R,3R)-(+)-4',5,7-trimethoxydihydroflavonol were isolated from the stem bark
of Lannea coromandelica, along with the known (2R,3R)-(+)-4',7-di-O
methyldihydroquercetin, (2R,3R)-(+)-4',7-di-O-methyldihydrokaempferol and (2R,3R)
(+)-4'-O-methyldihydroquercetin. All five compounds were isolated for the first
time from the genus Lannea; furthermore, (2R,3S)-(+)-3',5-dihydroxy-4',7
dimethoxydihydroflavonol, was a rare cis-type isomer. The structures of all
compounds were elucidated by spectroscopic methods including 2D NMR and CD
analysis.
PMID- 11014287
TI - Lignans from Mosla scabra.
AB - Two new cyclobutane-type lignans, named moslolignans A and B, together with two
known ones, andamanicin and magnosalin, were isolated from the whole plant of
Mosla scabra. Their structures were established as 1beta*,2beta*,3alpha*,4alpha*
1,2-dimethyl-3-(3- methoxy-4,5-methylene-dioxyphenyl)-4-(2,4,5-trimethoxyphenyl)
cycl obutane and 1beta*,2beta*,3alpha*,4alpha*-1,2-dimethyl-3-(2, 5-dimethoxy-3,4
methylenedioxyphenyl)-4-(2,4,5-trimethoxyphenyl)-cyclobu tane by spectroscopic
methods. This is the first report of naturally-occurring cyclobutane-type lignans
with asymmetrical substitutions.
PMID- 11014288
TI - Acylated delphinidin 3-rutinoside-5-glucosides in the flowers of Petunia reitzii.
AB - Two acylated anthocyanins were isolated from selected individuals of Petunia
reitzii, and identified to be delphinidin 3-O-[6-O-(4-O-(4-O-(6-O-(trans
caffeoyl)-beta-D-glucopyranosyl)-tr ans-p-coumaroyl)-alpha-L-rhamnopyranosyl)
beta-D-glucopyranoside]- 5-O-[beta-D-glucopyranoside] and delphinidin 3-O-[6-O-(4
O-(4-O-(beta-D-glucopyranosyl)-trans-p-coumaroyl)-alph a-L-rhamnopyranosyl)-beta
D-glucopyranoside]-5-O-[beta-D-glucopyranoside ]. Nine known anthocyanins were
also identified.
PMID- 11014289
TI - Anthocyanins in callus induced from purple storage root of Ipomoea batatas L.
AB - Two anthocyanins were isolated from the highly pigmented callus derived from the
storage root of purple sweet potato (Ipomoea batatas L.) cultivar 'Ayamurasaki'.
One was identified as cyanidin 3-O-sophoroside-5-O-glucoside, and the other as
cyanidin 3-O-(2-O-(6-O-(E)-p-coumaroyl-beta-D-glucopyranosyl)-beta-D-glucop
yranoside)-5-O-beta-D-glucopyranoside, by chemical and spectroscopic analysis.
PMID- 11014290
TI - Phenylpropanoid glycosides from Scrophularia ningpoensis.
AB - Three phenylpropanoid glycosides named ningposides A (3-O-acetyl-2-O-feruloyl
alpha-L-rhamnopyranose), B (4-O-acetyl-2-O-feruloyl-alpha-L-rhamnopyranose) and C
(3-O-acetyl-2-O-p-hydroxycinnamoyl-alpha-L-rhamnopyranose) along with the known
compounds sibirioside A, cistanoside D, angoroside C, acteoside,
decaffeoylacteoside and cistanoside F were obtained from the roots of
Scrophularia ningpoensis.
PMID- 11014291
TI - Tropane alkaloids from the leaves and stem bark of Erythroxylon alaternifolium
and Erythroxylon rotundifolium.
AB - A novel 3alpha,6beta,7beta-triol tropane alkaloid esterified by two benzoyl
residues was isolated from the leaves of the endemic cuban species, Erythroxylon
alaternifolium. Another novel 3alpha,6alpha,7beta-triol tropane alkaloid
esterified by trimethoxycinnamoyl and trimethoxybenzoyl residues was isolated
from the leaves and stem bark of a second endemic cuban species, Erythroxylon
rotundifolium. Their structures were elucidated as 3alpha,7beta-dibenzoyloxy
6beta-hydroxy-tropane and 3alpha-(3,4,5-trimethoxycinnamoyloxy)-7beta-(3,4,5-
trimethoxybenzoyloxy)-6alpha-hydroxy-tropane by spectroscopic methods including
2D-NMR techniques.
PMID- 11014292
TI - Structure revision of isoline (ruwenine), bisline and isolinecic acid.
AB - X-ray crystallography of bisline, and the chemical interconversion of bisline and
isoline (ruwenine), revealed that the structures previously assigned to these
alkaloids required revision; as did that of isolinecic acid.
PMID- 11014293
TI - Caffeine: also a fungal metabolite.
AB - Caffeine has been found to occur as a fungal metabolite and to be the principal
alkaloid in sclerotia of Claviceps sorghicola, a Japanese ergot pathogen of
Sorghum spp.
PMID- 11014294
TI - Indole alkaloids from a culture of the fungus Aporpium caryae.
AB - In a screening for antifungal metabolites, two indole compounds of mixed
biogenesis, 1H-indole-3-carboxylic acid, 1-(1,1-dimethyl-2-propenyl) methyl ester
and 1H-indole-3-carboxylic acid, 1-(2,3-dihydroxy-1,1-dimethylpropyl) methyl
ester were isolated from a culture of the basidiomycete Aporpiums caryae. The
structural elucidation of these compounds was accomplished by spectroscopic
methods.
PMID- 11014295
TI - Alkaloids from Crinum macowanii.
AB - Eleven alkaloids have been isolated from fresh bulbs of Crinum macowanii
(Amaryllidaceae). Macowine is reported here for the first time. The structure and
stereochemistry of this new alkaloid as well as of the known ones were determined
by physical and spectroscopic methods.
PMID- 11014296
TI - Four steroidal alkaloids from the leaves of Buxus sempervirens.
AB - Four new steroidal alkaloids, N20-formylbuxaminol E [(20S)-16alpha-hydroxy-20
(formylamino)-3beta-(dimethylamino)-9,10 -seco-buxa-9(11),10(19)-diene] (1), O16
syringylbuxaminol E [(20S)-16alpha-syringoyl-3beta-(dimethylamino)-20-(amino)-9,
10-seco-buxa-9(11),10(19)-diene] (2), N20-acetylbuxamine G [(20S)-20
(acetylamino)-3beta-(methylamino)-9,10-seco-buxa-9(11),1 0(19)-diene] (3) and N20
acetylbuxamine E [(20S)-20-(acetylamino)-3beta-(dimethylamino)-9,10-seco-buxa
9(11) ,10(19)-diene] (4) were isolated from the leaves of Buxus sempervirens.
Their structures were determined mainly on the basis of 2D NMR studies.
PMID- 11014297
TI - Alkaloids from Isopyrum thalictroides L.
AB - Three new bisbenzylisoquinoline alkaloids, isopyruthaldine, isopythaldine and
isothalmidine, containing new type of bridges were isolated from roots and
rhizomes of Isopyrum thalictroides. The known isoquinoline alkaloids, reticuline,
isocorydine. columbamine and palmatine, obtained from the aerial parts, are new
for the genus Isopyrum. All structures were elucidated by spectroscopic analysis.
PMID- 11014298
TI - Fatty acid amides from freshwater green alga Rhizoclonium hieroglyphicum.
AB - Freshwater green algae Rhizoclonium hieroglyphicum growing in the Ural Mountains
were examined for their fatty acid amides using capillary gas chromatography-mass
spectrometry (GC-MS). Eight fatty acid amides were identified by GC-MS. (Z)-9
octadecenamide was found to be the major component (2.26%).
PMID- 11014299
TI - Triterpenoids, essential oil and photo-oxidative 28 --> 13-lactonization of
oleanolic acid from Lantana camara.
AB - Two novel triterpenoids have been isolated from the roots of Lantana camara L.:
3beta,19alpha dihydroxy ursan-28-oic acid and 21,22beta-epoxy-3beta-hydroxy olean
12-en-28-oic acid in its methyl ester form. Its leaves have yielded an essential
oil which is rich in sesquiterpenes. Oleanolic acid, which is thought to be a
hepatoprotective compound, was isolated from L. camara roots and converted into
its 28 --> 13beta lactone by a facile photo-oxidation reaction.
PMID- 11014300
TI - Diarylheptanoids from Myrica arborea.
AB - Investigations of the stem and root bark of Myrica arborea (Myricaceae) have
yielded two novel diarylheptanoids, myricarborin and 11-O-beta-D
xylopyranosylmyricanol along with the known myricanol and 5-O-beta-D
glucopyranosylmyricanol. The structures of the novel compounds were determined by
spectroscopic methods.
PMID- 11014301
TI - Constituents of Chondria armata.
AB - A novel long chain fatty ester, pentyl hentriacontanoate 1 and an orange red
pigment, caulerpin 2 have been isolated and characterised from a red alga
Chondria armata. The pigment caulerpin hitherto known to be a constituent of
green algae of genus Caulerpa is being reported here for the first time from a
red alga.
PMID- 11014302
TI - C21 steroidal glycosides from Hemidesmus indicus.
AB - Two novel pregnane glycosides, denicunine (1) and heminine (4), have been
isolated from the dried stem of Hemidesmus indicus R.Br. (family:
Asclepiadaceae). Chemical transformations and spectroscopic evidence viz: 1H and
13C NMR spectroscopy and FABMS are consistent with the structures calogenin 3-O-3
O-methyl-beta-D-fucopyranosyl-(1-->4)-O-beta-D-oleandropyranosi de and calogenin
3-O-beta-D-cymaropyranosyl-(1-->4)-O-beta-D-digitoxopyranoside+ ++, respectively.
PMID- 11014303
TI - A 6-substituted-5,6-dihydro-2-pyrone from Cryptocarya strictifolia.
AB - The structure and absolute configuration of an alpha-pyrone isolated from
Cryptocarya strictifolia was elucidated as 6R-(4'R,6'R-dihydroxy-8'-phenyloct-1'
enyl)-5,6-dihydro-2H-pyran-2 -one. Pinocembrin and lysicamine were also isolated.
PMID- 11014304
TI - Fluorescence studies of ATP-diphosphohydrolase from Solanum tuberosum var.
Desiree.
AB - Chemical modification of potato apyrase suggests that tryptophan residues are
close to the nucleotide binding site. Kd values (+/- Ca2+) for the complexes of
apyrase with the non-hydrolysable phosphonate adenine nucleotide analogues,
adenosine 5'-(beta,gamma-methylene) triphosphate and adenosine 5'-(alpha,beta
methylene) diphosphate, were obtained from quenching of the intrinsic enzyme
fluorescence. Other fluorescent nucleotide analogues (2'(3')-O-(2,4,6
trinitrophenyl) adenosine 5'-triphosphate, 2'(3')-O-(2,4,6-trinitrophenyl)
adenosine 5'-diphosphate. 1,N6-ethenoadenosine triphosphate and 1,N6
ethenoadenosine diphosphate) were hydrolysed by apyrase in the presence of Ca2+,
indicating binding to the active site. The dissociation constants for the binding
of these analogues were calculated from both the decrease of the protein
(tryptophan) fluorescence and enhancement of the nucleotide fluorescence. Using
the sensitised acceptor (nucleotide analogue) fluorescence method, energy
transfer was observed between enzyme tryptophans and ethene-derivatives. These
results support the view that tryptophan residues are present in the nucleotide
binding region of the protein, appropriately oriented to allow the energy
transfer process to occur.
PMID- 11014305
TI - Trauma and pressure explain the clinical presentation of the Graves' disease
triad.
PMID- 11014306
TI - Impaired response to hepatocyte growth factor in FRTL-5 rat thyroid cells
expressing a functional hepatocyte growth factor receptor.
AB - The FRTL-5 rat thyroid cell line is widely used for studies of thyrocyte function
and growth. The objective of the present study was to investigate the effects of
hepatocyte growth factor (HGF) on FRTL-5 cells. HGF has previously been known to
be a potent regulator of thyrocyte growth and differentiation. Met, the receptor
for HGF was expressed in FRTL-5 cells, as well as in primary cultures of porcine
thyrocytes included in the study as control. On HGF stimulation Met was tyrosine
phosphorylated in both porcine and FRTL-5 cells, indicating an activation of the
receptor. Addition of HGF induced changes of cell shape, scattering and
proliferation of the porcine thyrocytes, but not in the FRTL-5 cells; yet, a
functional coupling of Met to the p85 subunit of the phosphatidylinositol-3'
kinase (PI3'-K) in coprecipitation experiments, formation of focal adhesions
detected in immunofluorescence staining with an antivinculin antibody, and
induction of c-fos mRNA in Northern blot analysis was observed in FRTL-5 cells,
showing a transduction of the HGF/Met signal. In summary, despite the expression
of apparently functional Met, the FRTL-5 cells are unable to properly respond to
HGF.
PMID- 11014307
TI - Thyroid hormones influence serum leptin levels in patients with Graves' disease
during suppression of beta-adrenergic receptors.
AB - Leptin is a protein product of the ob gene, mainly produced by adipocytes. Leptin
is thought to play an important role in the homeostasis of body weight by
suppressing appetite and increasing energy consumption. The aim of this study was
to investigate the possible effect of thyroid hormone on the regulation of the
leptin system during suppression of beta-adrenergic receptors in Graves'
patients. We studied 15 adult female patients with Graves' disease. Thyroid
function, serum levels of leptin, and percent body fat (%BF) were examined at
four different clinical conditions during therapy (A, untreated; B, beta
adrenergic antagonist only [A, B; hyperthyroid], C, beta-adrenergic antagonist
and antithyroid drug; D, antithyroid drug only [C, D; euthyroid]). The use of
beta-adrenergic antagonist significantly reduced heart rate in spite of
hyperthyroid state, indicating sufficient suppression of beta-adrenergic
receptors. During treatment with beta-adrenergic antagonist, leptin percentage of
body fat (%BF) ratio significantly decreased in euthyroid state compared to that
in hyperthyroid state (from 38.7 +/- 21.3 to 18.1 +/- 19.3, p = 0.003). Moreover,
there was a significantly positive correlation between delta leptin/%BF and delta
free thyroxine (FT4) (r = 0.51, p = 0.008). Under a euthyroid state induced by
antithyroid drug treatment, leptin/%BF did not change in spite of withdrawal of
beta-adrenergic antagonist. Our data indicate that thyroid hormones could
increase serum leptin level during suppression of beta-adrenergic receptors in
Graves' patients. Our data also suggest that the beta-adrenergic action of
thyroid hormones might be partly mediated by regulation of leptin.
PMID- 11014308
TI - The somatostatin analogue octreotide modulates Iodothyronine deiodinase activity
and pituitary neuromedin B.
AB - Somatostatin inhibits growth hormone and thyrotropin (TSH) secretion. It also
enhances the inhibitory effect of thyroid hormone (TH) on TSH by poorly
understood mechanisms. We investigated the acute effect of the long-acting
somatostatin analogue, octreotide (OCT), on anterior pituitary type 1 (D1) and 2
(D2) deiodinase activity, on liver D1, and on pituitary content of neuromedin B
(NB), an autocrine inhibitor of TSH secretion, which is positively regulated by
thyroid hormones. Euthyroid or hypothyroid rats were sacrificed at different
times after a single subcutaneous injection of OCT (1 microg/kg body weight
[BW]). D1 and D2 activities were measured by the release of 125I from 125I
reverse triiodothyronine (rT3) under different assay conditions. NB, TSH, T3, and
thyroxine (T4) were quantitated by radioimmunoassay (RIA). In euthyroid rats,
liver and pituitary D1 activities were decreased (50%) 6 hours after OCT
injection; pituitary D2 and NB remained unchanged. In hypothyroid rats, OCT
increased near to the level of normal rats both pituitary D1 activity (but not
liver) and NB content, at 24 hours and at 6 and 24 hours, respectively (p <
0.05). Pituitary D2, greatly increased by hypothyroidism, showed a small (25%)
but significant reduction at 3 hours, persisting at 24 hours (p < 0.01), although
it remained higher than that of euthyroid control. Serum thyroid hormones were
not affected by OCT injection. The results show that octreotide acutely regulates
pituitary deiodinases and NB content, both representing mechanisms that
potentially can contribute to somatostatin and octreotide actions on pituitary
growth hormone (GH) and TSH secretion and to modulate these cells sensitivity to
thyroid hormone action.
PMID- 11014309
TI - Sensitive thyroid-stimulating antibody assay in whole serum containing five
percent polyethylene glycol using porcine thyroid cells.
AB - Previously we reported that the amounts of cyclic adenosine monophosphate (cAMP)
production by polyethylene glycol (PEG) 22.5% precipitated fraction (PF) (crude
immunoglobulin G [IgG]) from thyroid-stimulating antibody (TSAb)-positive serum
were higher than those by PEG 12.5% PF, and that PEG (5%) augmented affinity
purified TSAb-IgG-stimulated cAMP production in porcine thyroid cells (PTC)
assay. In the present work, we studied sensitive TSAb assay using whole sera in
the presence of high PEG concentrations in PTC assay. cAMP produced by TSAb
positive serum increased in proportion to serum amounts up to 0.05 mL, but
gradually decreased in 0.075 mL. The maximal augmentative effect of PEG on TSAb
positive serum (0.05 mL)-stimulated cAMP production was found in 5% PEG (final).
Thus, TSAb assay using whole serum (0.05 mL) in the absence of 5% PEG (serum
method) and sensitive TSAb (sTSAb) assay using whole serum (0.05 mL) in the
presence of 5% PEG (serum plus 5% PEG method) were performed. The sensitive
thyroid-stimulating antibody (sTSAb) activities of Graves' sera showed
significantly higher (twofold to sevenfold) compared to simple TSAb activity with
sera. sTSAb and TSAb activities were positive in 91% (29/32) and 47% (15/32) of
untreated Graves' patients with hyperthyroidism. The sTSAb activities by serum
plus 5% PEG method were higher than that by PEG 12.5% precipitated fraction (PF)
from test serum (0.2 mL) in many Graves' sera, but lower than that by PEG 22.5%
PF from test serum (0.2 mL). PEG (5%) did not augment cAMP produced by high TSH
serum (127-210 mU/L) in thyroiditis chronica. sTSAb activity was negative in
adenomatous goiter, subacute thyroiditis, and thyroid cancer. sTSAb activity was
also negative in TSH stimulation blocking antibody (TSBAb)-positive
hypothyroidism (during thyroxine [T4] treatment), but was positive in Graves'
sera with coexistence serum of TSAb and TSBAb because of augmentative effect of
5% PEG on TSAb activity. This assay in whole serum (0.05 mL) containing 5% PEG is
less sensitive than sensitive TSAb assay using PEG 22.5% PF from test serum (0.2
mL), but this method can be available clinically as routine TSAb assay using
whole serum because of the technical simplicity.
PMID- 11014310
TI - The effect of short-term low-dose perchlorate on various aspects of thyroid
function.
AB - Perchlorate (ClO4) salts are found in rocket fuel, fireworks, and fertilizer.
Because of ground water contamination, ClO4 has recently been detected in large
public water supplies in several states in the 4-18 microg/L (parts per billion
[ppb]) range. The potential adverse effect of chronic low level ClO4 ingestion on
thyroid function is of concern to the Environmental Protection Agency (EPA). The
daily ingestion of ClO4 at these levels would be magnitudes below the therapeutic
effect level of hundreds of milligrams of ClO4 used in treating hyperthyroidism.
Studies were carried out in nine healthy male volunteers who had normal thyroid
function and negative thyroid antibodies to determine whether the ingestion of 10
mg of ClO4 daily (approximately 300 times the estimated maximum amount of ClO4
consumed from the affected water supplies) would affect any aspect of thyroid
function. They ingested 10 mg of ClO4 dissolved in a liter of spring water during
waking hours for 14 days. Baseline serum thyrotropin (TSH), free thyroxine index
(FTI), total triiodothyronine (TT3), 4-, 8-, and 24-hour thyroid 123I uptakes
(RAIU), serum and 24-hour urine ClO4, 24-hour urine iodine, complete blood count
(CBC), and chemistry profile were determined. All blood and urine tests were
repeated on days 7 and 14 of ClO4 administration and thyroid RAIU on day 14 of
ClO4 administration. All tests were repeated 14 days after ClO4 was discontinued.
No effect of ClO4 on serum thyroid hormone or TSH concentrations, urinary iodine
excretion, CBC, or blood chemistry was observed. Urine and serum ClO4 levels were
appropriately elevated during the course of ClO4 ingestion in all subjects,
demonstrating compliance. By day 14 of ClO4 administration, the 4-, 8-, and 24
hour thyroid RAIU values decreased in all nine subjects by a mean value of 38%
from baseline and rebounded above baseline values by 25% at 14 days after ClO4
withdrawal (p < 0.01 analysis of variance (ANOVA) and Tukey). It is well known
that the major effect of ClO4 on the thyroid is a decrease in the thyroid iodide
trap by competitive inhibition of the sodium iodide symporter (NIS). The present
study demonstrates the sensitivity of the thyroid iodide trap to ClO4 because a
low dose of 10 mg daily significantly decreased the thyroid RAIU without
affecting circulating thyroid hormone or TSH concentrations. It is possible,
however, that the daily consumption of low levels of ClO4 in drinking water over
a prolonged period of time could adversely affect thyroid function but no
evidence of hypothyroidism was observed at 10 mg of ClO4 daily in this 2-week
study. It is now of interest to determine a no effect level for ClO4 on the
inhibition of the thyroid RAIU and to carry out a long-term ClO4 exposure study.
PMID- 11014311
TI - Cardiovascular and atherogenic aspects of subclinical hypothyroidism.
AB - Subclinical hypothyroidism (SH) is common, especially among elderly women. There
is no clear evidence to date that SH causes clinical heart disease. However, mild
thyroid gland failure, evidenced solely by elevation of the serum thyrotropin
(TSH) concentration, may be associated with increased morbidity, particularly for
cardiovascular disease, and subtly decreased myocardial contractility. In SH,
both cardiac structures and function remain normal at rest, but impaired
ventricular function as well as cardiovascular and respiratory adaptation to
effort may become unmasked during exercise. These changes are reversible when
euthyroidism is restored. Flow-mediated vasodilatation, a marker of endothelial
function, is significantly impaired in SH, and decreased heart rate variability,
a marker of autonomic activity, suggests hypofunctional abnormalities in the
parasympathetic nervous system. SH does result in a small increase in low-density
lipoprotein (LDL) cholesterol (C) and a decrease in high-density lipoprotein
(HDL)-C, changes that enhance the risk for development of atherosclerosis and
coronary artery disease (CAD). After coronary revascularization, a trend toward
higher rates of chest pain, dissection, and reocclusion has been noted in SH
subjects. Smoking may contribute to the high incidence of SH and may aggravate
its metabolic effects. Subjects with SH with marked TSH elevation and high titers
of thyroid autoantibodies are at higher risk of unnoticed progression to overt
hypothyroidism. Especially women over 50 years with TSH levels greater than 10
mU/L and smoking habits have the highest risk for cardiovascular complications.
The magnitude of the lipid changes and the subtle impairment of left ventricular
function and cardiopulmonary exercise capacity in SH may justify use of hormone
replacement. Early levothyroxine (LT4) treatment in SH may reduce the C level by
an average of 8% and normalize all metabolic effects in smokers, nevertheless, in
some patients, LT4 therapy may exacerbate angina pectoris or an underlying
cardiac arrhythmia. Longitudinal follow-up to define the actual cardiovascular
disease risk associated with SH is warranted.
PMID- 11014312
TI - Complacency: the most dangerous enemy in the war against iodine deficiency.
PMID- 11014313
TI - Elephantiasic pretibial myxedema: insight into and a hypothesis regarding the
pathogenesis of the extrathyroidal manifestations of Graves' disease.
AB - The basis for the extrathyroidal manifestations of Graves' ophthalmopathy (GO)
and dermopathy are not well understood. We describe immunohistochemical studies
on the skin of a patient with an extreme, elephantiasic form of Graves'
dermopathy that developed after periods of prolonged standing with dependent
edema. Excision of part of the lesion with subsequent skin grafting from a normal
donor site resulted in recurrence of the disease at the original site as well as
in development of disease at the donor site. A murine monoclonal antibody reacted
with the thyrotropin receptor (TSHR) or a cross-reacting protein in fibroblast
like cells in the patient's upper dermis and, surprisingly, with dermal cells
from unaffected individuals. The patient's dermis containing lymphoid follicles
comprising B cells and CD3+, CD4+ T cells, with few CD8+ T cells. CD21+ cells
(most likely follicular dendritic cells) were also present in the dermis. Based
on past and present observations, we raise an unifying hypothesis to explain the
diverse extrathyroidal manifestations of Graves' disease and their apparent lack
of association with TSHR autoantibodies. As opposed to the present concept that
these phenomena relate to site-specific properties on preadipocytes or
fibroblasts, we suggest that clinically evidence GO and dermopathy are primarily
caused by local factors (particularly in the orbit) superimposed on a systemic,
low-grade connective tissue inflammation.
PMID- 11014314
TI - Atypical hypothyroidism and the very low birthweight infant.
AB - Results of thyroid screening tests were examined retrospectively on 311,282
infants born in Massachusetts from January 1, 1993 to December 31, 1996. During
this period, 118 infants were found to have typical hypothyroidism, characterized
by a low thyroxine (T4) and an elevated thyrotropin (TSH) on the initial newborn
screening specimen. Of these, 98 were normal birthweight (NBW, > or = 2,500 g), 9
were low birthweight (LBW, 1,501-2,499 g), and 11 were very low birthweight
(VLBW, < or = 1,500 g). Atypical hypothyroidism as defined here is characterized
by a low T4 and normal TSH concentration on the initial screening specimen,
followed by and elevated TSH level on a repeat blood specimen. This phenomenon
occurred in 18 infants, of whom 4 were NBW, 4 were LBW, and 10 were VLBW. The
incidence of combined typical and atypical hypothyroidism was: NBW, 1:3051; LBW,
1:1589; VLBW, 1:153, with the highest incidence of atypical hypothyroidism in the
VLBW category (48% of cases in this weight category, 56% of all cases of atypical
hypothyroidism). In addition, screening programs using a primary TSH screen will
miss infants with atypical hypothyroidism. In view of these results, it is
suggested that T4 measurements be obtained routinely in all LBW and VLBW infants,
with additional routine repeat blood specimens.
PMID- 11014315
TI - Review of thyroid cancer cases among patients with previous benign thyroid
disorders.
AB - A previous register linkage study showed an increased risk of thyroid cancer
among patients previously discharged from a hospital with a diagnosis of a benign
thyroid disorder. In this study, we have reviewed all available medical records,
first to validate the earlier result and second to describe the symptomatology of
patients with a history of benign thyroid disorder prior to the cancer diagnosis.
The previous study identified 189 patients with a benign and subsequent malignant
thyroid disorder. Medical records were obtainable for 156 of these patients and
were reviewed. For 104 patients, benign and malignant thyroid diseases were
metachronous (a clearly separated disease history of the benign and malignant
diseases), and for 48 patients synchronous. In 4 cases, thyroid cancer could not
be confirmed. Among patients with metachronous thyroid disorders, all major
benign thyroid disorders were represented including hot nodules, diffuse and
multinodular toxic and nontoxic goiter. Symptoms preceding diagnosis of thyroid
cancer included growth of goiter/nodules, globulus, stridor, hoarseness, and
metastasis. No major differences were found among patients with metachronous and
synchronous benign and malignant thyroid disorder, apart from the fact that all
metastases were found among metachronous cases. This study confirmed the
conclusion that patients with a previous history of goiter or nodules have an
increased risk of thyroid cancer. However, thyroid cancer still occurs too
infrequently to warrant screening in all patients with a previous history of
goiter or nodules.
PMID- 11014316
TI - Changes in cytokine production during pregnancy in patients with Graves' disease.
AB - In order to investigate the role of type 1 and type 2 cytokines in the remission
of Graves' disease (GD) during pregnancy, spontaneous and mitogen-stimulated
production of interleukin (IL)-4, IL-6, IL-10, IL-12, interferon-gamma (IFN
gamma), and tumour necrosis factor-alpha (TNF-alpha) were measured by enzyme
linked immunospot assay of peripheral blood mononuclear cells from 10 pregnant
women with GD, 8 healthy pregnant women, and 10 healthy nonpregnant women. Tests
were performed in the first, second, and third trimesters of pregnancy and 10-17
weeks after delivery. IL-4 production was not affected greatly by normal or GD
pregnancy, whereas IFN-gamma production was suppressed throughout pregnancy but
returned to normal levels after delivery in both controls and patients. IL-6 and
TNF-alpha tended to be higher in GD pregnancy than normal pregnancy, especially
in the second and third trimesters. Controls had raised IL-10 in the first
trimester with a return to normal levels by the third trimester, whereas patients
had raised levels throughout pregnancy. IL-12 levels were suppressed to a greater
extent in control than Graves' pregnancy, especially during the second and third
trimesters. Ratios of IL10:IL12 in phytohemaglutinin (PHA)-stimulated cultures
were much lower in GD than normal pregnancy and cross-regulation of IL-10 and IL
12 may be deficient in GD.
PMID- 11014317
TI - Risk factors for malignancy of thyroid nodules initially identified as follicular
neoplasia by fine-needle aspiration: results of a prospective study of one
hundred twenty patients.
AB - Indeterminate or suspicious findings on fine-needle aspiration (FNA) of nodular
thyroid disease (i.e., findings that neither give immediate indication for
surgery nor lead to clear-cut conservative management) have been the key
diagnostic problem in thyroid cytology for which the inability to differentiate
cytologically benign from malignant follicular growth has been one reason. The
aim of this cohort study of 120 consecutive (103 females, 17 males) patients with
palpable nodular thyroid disease diagnosed as follicular neoplasia (FN) by FNA
(defined by the triad of high numbers of follicular cells, microfollicular
arrangement, and scanty or absent colloid) was to identify patients at high risk
for malignancy based on the prospective evaluation of clinical features and to
characterize the histologic entities of FN. Based on a 100% surgery rate we found
an 18% malignancy rate (12 papillary carcinomas, 9 follicular carcinomas).
Previously suggested factors with elevated risk for malignancy such as extremes
of age, male gender, and large nodule size were not associated with increased
risk as were cold nodules by 99mTc-scintigraphy (relative risk: 1.2, 95%
confidence interval [CI] 0.4-3.3). However, hard lesions to palpation (relative
risk 2.6, 95% CI: 1.2-5.6), solitary (relative risk: 2.6, 95% CI: 1.7-4.0), and
hypoechoic FNs (relative risk: 3.4, 95% CI: 2.0-5.7) by ultrasound showed
elevated risks of malignancy. In summary, suspicious palpation or ultrasound
results may help to define a subgroup of patients with elevated risk of
malignancy when FNA indicates the diagnosis of follicular neoplasm of the
thyroid.
PMID- 11014318
TI - Acute interstitial nephritis and fatal Stevens-Johnson syndrome after
propylthiouracil therapy.
AB - We report a case of acute interstitial nephritis and fatal Stevens-Johnson
syndrome in a 90-year-old woman with amiodarone-induced hyperthyroidism, who had
been treated for 5 weeks with propylthiouracil (PTU). On admission, the patient
exhibited acute renal failure and generalized macular purpuric eruption. Acute
interstitial nephritis and Stevens-Johnson syndrome were diagnosed and PTU
withdrawn. Although renal function recovered after PTU withdrawal and
corticosteroid therapy, the patient's condition worsened, and she died after
developing multiple organ failure. Acute interstitial nephritis seems to be
rarely associated with PTU therapy. Moreover, a literature review suggested that
this could represent the first published report of a Stevens-Johnson syndrome
developing during PTU therapy.
PMID- 11014319
TI - Primary non-Hodgkin's T-cell lymphoma of the thyroid gland complicating
Hashimoto's thyroiditis: case report.
AB - This case report presents an extremely rare case of primary non-Hodgkin's T-cell
lymphoma of the thyroid gland complicating Hashimoto's thyroiditis and discusses
the clinical history, findings, treatment, and prognosis. Although the place of
surgery in the treatment of thyroid lymphoma is controversial, in this case,
surgery followed by three rounds of chemotherapy with cyclophosphamide,
doxorubicin, vincristine, and prednisone, and radiation therapy to neck and
mediastinum were a very effective treatment for the disease so that no relapse
has been detected during 3-year follow-up.
PMID- 11014320
TI - Subclinical hyperthyroidism.
PMID- 11014321
TI - Images in thyroidology. Medullary thyroid cancer arising in an adenoma.
PMID- 11014322
TI - Environmental iodine deficiency: A challenge to the evolution of terrestrial
life?
PMID- 11014323
TI - Pharmacokinetics of orally and intravenously administered telmisartan in healthy
young and elderly volunteers and in hypertensive patients.
AB - A series of studies was conducted in healthy young males and healthy elderly
males or females to evaluate the pharmacokinetic profile of telmisartan. In
addition, two phase-II clinical trials assessed the pharmacokinetics and the
safety of telmisartan in mild-to-moderate hypertensive patients. Telmisartan was
given as a single oral (1-160 mg) or intravenous (10-160 mg) dose to young males.
In another multiple-dose study, telmisartan 320 mg was administered orally once
daily for 7 days to healthy young male subjects. Elderly subjects received oral
telmisartan (20 and 120 mg) once daily for 7 days. Telmisartan doses of 10, 20,
40, 80, 120 and 160 mg were taken once daily by mild-to-moderate hypertensive
patients for 7 days. Additionally, oral telmisartan (40, 80 or 120 mg) was
administered once daily for 28 days to hypertensive subjects. Following oral
dosing, median time to maximum plasma telmisartan concentration was 0.5 - 2 h,
with maximum plasma concentrations increasing disproportionately with dose. By
contrast, plasma concentrations were directly related to the intravenous dose.
Steady state was observed after 5-7 days of once-daily administration, and there
was no clinically relevant accumulation at 28 days. The plasma concentration-time
profiles were similar in all study groups and were characterized by fast
absorption and a rapid biexponential decline after the peak plasma concentration,
with a prolonged terminal elimination phase (> 20 h in healthy and hypertensive
subjects). Telmisartan was well tolerated, with a low incidence of drug-related
adverse events. The most frequent event was headache, which also occurred in
placebo-treated control subjects. No changes in heart rate, electrocardiograms or
clinical chemistry were detected following receipt of telmisartan. The study thus
shows that high systemic levels of telmisartan, which are well tolerated, can be
attained in healthy adults of any age and in hypertensive subjects. The long
terminal elimination half-life makes telmisartan suitable for once-daily dosing
and contributes to the sustained efficacy over the full 24-h dosing interval.
PMID- 11014324
TI - Vacuolar hepatocyte degeneration induced by infusion of 20% glucose solution with
insulin after hepatopancreatectomy in rats.
AB - To investigate the causes of hepatic dysfunction after extensive resection of the
liver together with pancreatectomy, rats were subjected to sham operation, to 68%
hepatectomy alone, to 90% pancreatectomy alone, or to 68% hepatectomy combined
with 90% pancreatectomy (hepatopancreatectomy). Solutions of 5% or 20% glucose
were infused post-operatively for 48 h at a constant rate (250 ml/kg body
weight/day) under fasting conditions. To improve the survival rates of
pancreatectomized and hepatopancreatectomized rats given 20% glucose, it was
necessary to use insulin. In hepatopancreatectomized rats, infusion of 20%
glucose with insulin (1 U/5 g glucose) induced prominent hepatocyte vacuolar
degeneration and mitochondrial swelling, associated with reduced hepatic protein
content. The severity of histological changes was proportional to the insulin
dose and the activity of hepatic glucokinase, a key glycolytic enzyme. were
observed in These histological changes pancreatectomized rats albeit in a milder
form, but not in sham-operated or hepatectomized rats given 20% glucose nor in
any rats given 5% glucose. Our results suggest that hepatopancreatectomy followed
post-operatively by a high glucose load and exogenously administered insulin
enhances the development of hepatocyte swelling.
PMID- 11014325
TI - Standard melatonin intake and circadian rhythms of elite athletes after a
transmeridian flight.
AB - Many transmeridian travellers, including top athletes, regularly take melatonin
to reduce negative jet lag symptoms. Standard (rather than individually tailored)
doses are often used. We examined the effects of a standard dose of melatonin on
the body temperature rhythms of 12 elite biathletes (eight men and four women)
after an eastward transmeridian flight to an international competition. The
different effects on body temperature rhythms in men versus women underscore the
need for personalized dosing schedules to avoid potential undesirable
consequences.
PMID- 11014326
TI - Predominant Staphylococcus aureus isolated from various skin diseases.
AB - We examined predominant Staphylococcus aureus isolated from lesions of various
skin diseases, and during the past 3 years, 113 methicillin-sensitive and 31
methicillin-resistant S. aureus have been isolated. The predominant species
isolated from almost all of the primary bacteriological cultures was S. aureus.
The skin diseases from which cultures were most frequently prepared were atopic
dermatitis, followed by ulcers. S. aureus was the predominant species in two
thirds or more of cases of all of the different skin diseases examined. The
predominant species identified, other than S. aureus, included Streptococcus
species and Pseudomonas aeruginosa. Evaluation of the predominance of S. aureus
is important to the determination of the severity of skin lesions and, if needed,
appropriate antimicrobial therapy.
PMID- 11014327
TI - Case of ulcerative colitis associated with oesophageal ulcer.
AB - A case of ulcerative colitis complicated by oesophageal ulcers is reported. A
woman was admitted to our hospital because of exacerbations of ulcerative colitis
both in 1992 (aged 15 years) and 1995 (aged 18 years). When she was admitted in
1995 she complained of bloody diarrhoea, sore throat and pain on swallowing.
Oesophagogastro-duodenoscopy revealed oesophageal ulcers. Oesophageal pH
monitoring (24-h) showed no evidence of gastro-oesophageal reflux disease. After
the patient was treated she with oral prednisolone showed considerable
improvement clinically and endoscopically. Initial dosage was 60 mg/day, and 1
week later, the dosage was gradually dropped since the patient responded
favourably. The improvement of the oesophageal lesions coincided with the
remission of ulcerative colitis. The oesophageal ulcers are, therefore, thought
to be an extracolonic manifestation of ulcerative colitis.
PMID- 11014329
TI - Magnetic resonance assessment of acute and chronic stroke.
AB - This article describes the important role of magnetic resonance imaging (MRI) in
noninvasively assessing human focal ischemic stroke. Conventional MRI, diffusion
weighted and/or perfusion-weighted imaging have been used to facilitate both the
qualitative and quantitative evaluation of heterogeneity of ischemic brain
tissue. Further, by combining 2 or more magnetic resonance parameters, tissue
signature models have been developed that may be used as surrogate markers of
tissue histopathology to characterize ischemic tissue as salvageable, necrotic,
or tissue in transition to necrosis. Magnetic resonance tissue-signature models
and results are presented. Dynamic changes in the evolution of ischemic tissue to
infarction are also discussed. Recovery from acute stroke was studied with blood
oxygenation level-dependent functional MRI to investigate the neural mechanisms
for recovery from aphasia after stroke.
PMID- 11014328
TI - Neurologic complications of cardiac surgery.
AB - The average age of patients undergoing cardiac surgery and the number of
comorbidities they possess will continue to increase as surgical technology
advances. Toxic/metabolic encephalopathy, hemispheric strokes, hypoxic injury,
and peripheral nerve lesions all can occur as a result of cardiac surgery.
Therefore, an understanding of the neurologic risk, recognizable syndromes, and
preventative measures will continue to be important. Careful preoperative
assessment, operative risk factor reduction, and careful postoperative
assessments and management may reduce the neurologic risk for cardiac surgery.
PMID- 11014330
TI - Transcranial Doppler assessment of cerebral embolic disorders.
AB - Transcranial Doppler ultrasound allows noninvasive monitoring of the large
intracranial vessels. Microembolic signals (MES) have been observed under a
variety of circumstances, especially in symptomatic carotid stenosis, high-risk
cardiac conditions, and surgical procedures (such as carotid endarterectomy and
cardiopulmonary bypass surgery). Technical considerations have presented numerous
challenges to the interpretation of these signals, many of which appear to
represent small emboli traveling in the blood flow. The technical aspects of
these MES are discussed and their significance in relation to cerebral ischemia
and its prevention are examined in some detail.
PMID- 11014331
TI - Cardiomyopathy in AIDS: a pathophysiological perspective.
AB - This report addresses issues of pathogenesis, pathophysiology, and epidemiology
of an increasingly prevalent cardiomyopathy in acquired immunodeficiency syndrome
(AIDS). As patient survival increases with more effective antiretroviral therapy,
cardiomyopathy in AIDS will become more apparent. The interactions of cellular
and organism factors in AIDS and their relationships to the development of
cardiomyopathy are reviewed herein. Amongst the factors addressed in this review
are: (1) comorbid conditions found with AIDS, (2) the role of inflammatory heart
disease and cytokines in the development of AIDS cardiomyopathy, (3) the
pathogenetic role of vascular cells and myocardial cells in the development of
cardiomyopathy, (4) the role of myocardial retroviral infection in AIDS, and (5)
the impact of toxicity from antiretroviral therapy on the development of
cardiomyopathy. Because it is possible that more than 1 of these factors is
present in a given patient inflicted with AIDS, a multifactorial pathogenesis in
AIDS cardiomyopathy must be considered.
PMID- 11014333
TI - Hot off the press.
PMID- 11014332
TI - Current status of safety and efficacy of calcium channel blockers in
cardiovascular diseases: a critical analysis based on 100 studies.
AB - Recently, serious concerns have been expressed about the long-term safety of the
calcium channel blockers (CCBs) as a group. Safety and efficacy are, however,
ultimately linked to each other; therefore both must be evaluated especially in
the therapy of angina and hypertension, the main clinical indications for CCBs.
The structural, functional, and pharmacokinetic heterogeneity of CCBs means that
the efficacy and dangers of one subclass, such as the short-acting
dihydropyridines (DHPs), in one situation, such as unstable angina, do not
necessarily apply in other clinical situations. One hundred studies are reviewed
according to their methods of data collection: case series, case control, cohort,
randomized controlled trials (RCTs), and meta-analyses. Large, well-designed RCTs
and the meta-analyses based on these trials remain the gold standard.
Observational studies, though potentially less reliable sources of information
because of selection bias, may nevertheless produce hypotheses that must then be
tested in RCTs. Regarding safety, both observational studies and RCTs suggest
that adverse effects of CCBs may be linked to short-acting agents, specifically
short-acting nifedipine. Two good studies favor the safety of verapamil, even in
short-acting form. Incomplete but increasing overall evidence favors the safety
of longer-acting DHPs. Heart failure remains a class contraindication to the use
of all CCBs, with some exceptions. Regarding efficacy, there are positive results
of RCTs with CCBs in 2 specific clinical situations, namely, verapamil in
postinfarct protection in the absence of pre-existing heart failure, and 2
outcome studies on hypertension with longer acting DHPs. These results cannot
automatically be applied to other clinical situations and to other CCBs. For
example, there is no evidence for the safety or efficacy of DHPs used without
beta blockers in postinfarct patients. In diabetic hypertensives, 2 relatively
large RCTs show that the blood pressure can be reduced by DHP-based therapy in
diabetics, with a reduction in hard end points. To achieve current blood pressure
goals, combination therapy is almost always necessary, and in diabetics there is
strong evidence that 1 essential component should be an angiotensin converting
enzyme inhibitor. The future aim with CCBs must be to obtain a large database
gathered from RCTs, which will give the same certainty about efficacy and safety
that already holds for use of the diuretics in hypertension, beta-blockers in
postmyocardial infarction patients, and the angiotensin converting enzyme
inhibitors in heart failure.
PMID- 11014334
TI - Do mammals make their own morphine?
PMID- 11014335
TI - Nonlantibiotic antibacterial peptides from lactic acid bacteria.
PMID- 11014336
TI - The global chloromethane cycle: biosynthesis, biodegradation and metabolic role.
PMID- 11014337
TI - Biomimetic synthesis of alkaloids.
PMID- 11014338
TI - The iron(II) and 2-oxoacid-dependent dioxygenases and their role in metabolism.
PMID- 11014339
TI - Monoterpenoids.
PMID- 11014340
TI - Recommendations for the medical management of osteoarthritis of the hip and knee:
2000 update. American College of Rheumatology Subcommittee on Osteoarthritis
Guidelines.
PMID- 11014341
TI - The role of the chondrocyte in osteoarthritis.
PMID- 11014342
TI - The course of radiologic damage during the first six years of rheumatoid
arthritis.
AB - OBJECTIVE: To describe the radiologic course in a large cohort of patients with
early rheumatoid arthritis (RA) and to analyze individual components of damage.
METHODS: Five hundred two patients with recent-onset RA (disease duration <1
year) underwent annual radiologic assessment for a maximum of 6 years in this
longitudinal prospective study. The study was designed to investigate the
efficacy of 3 different therapeutic strategies. For the assessment of radiologic
damage, radiographs of the hands and feet were scored according to the modified
Sharp/van der Heijde method (SHS; range 0-448). A mean of 2.9 (range 1-7)
radiographs was read per patient. RESULTS: Stable rates of progression of the
SHS, erosion score, and narrowing score were found over the course of RA: the
mean rates were 8.6, 5.4, and 3.2 modified Sharp units per year, respectively.
The rate of progression of newly (not previously) damaged joints declined, and
the rate of progression of already damaged joints (which became more damaged)
increased during followup, leading to an equal contribution to progression of the
SHS at 5 years. The joints of the feet, especially the fifth metatarsophalangeal
joint, generally became eroded earlier and more of them became eroded compared
with the joints of the hands. CONCLUSION: Radiologic damage progresses at a
constant rate. In advanced disease, monitoring the progression of previously
existing damage is as important as assessing new abnormalities in previously
undamaged joints. Radiographs of the feet should be included in assessments of
radiologic damage that are used in clinical intervention trials and daily
practice.
PMID- 11014343
TI - The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor alpha
expression in macrophages by inducing apoptosis.
AB - OBJECTIVE: Sulfasalazine (SSZ) is a commonly used drug in the treatment of
inflammatory diseases such as rheumatoid arthritis and Crohn's disease. In both
diseases, the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha)
plays a prominent role. In these studies, we investigated the mechanism by which
SSZ inhibits TNFalpha expression in macrophages and macrophage-like cell lines.
METHODS: Monocyte-derived macrophages and several macrophage-like cell lines were
exposed to SSZ in vitro, and the effect on TNFalpha expression was monitored by
reverse transcriptase-polymerase chain reaction and Western blot analysis. In
addition, the effects of SSZ in vivo were examined by intraperitoneally injecting
mice with SSZ, after which peritoneal cells were harvested and examined using
various staining methods. RESULTS: Preincubation of macrophages with SSZ, but not
with methotrexate, inhibited lipopolysaccharide (LPS)-induced TNFalpha
expression. Inhibition of TNFalpha expression by SSZ coincided with the induction
of apoptosis, as judged by the appearance of morphologic changes typical of
apoptosis, such as nuclear condensation and fragmentation. Induction of apoptosis
by SSZ was confirmed by TUNEL analysis and by the detection of cleaved U1-70K, a
substrate of caspase 3. Intraperitoneal injections of SSZ in mice resulted in the
induction of apoptosis of peritoneal cells within a few hours. SSZ-induced
cleavage of the U1-70K protein was inhibited by Zn2+ and by specific inhibitors
of caspases 3 and 8, but not caspases 1 and 9. Interestingly, the reduced
expression of LPS-induced TNFalpha in the presence of SSZ was restored by
inhibition of caspase 8. CONCLUSION: Inhibition of TNFalpha expression in
macrophages by SSZ is due to the induction of apoptosis and involves the
activation of caspase 8.
PMID- 11014344
TI - Synovial macrophage depletion with clodronate-containing liposomes in rheumatoid
arthritis.
AB - OBJECTIVE: To assess whether intraarticular (IA) administration of clodronate
liposomes results in local macrophage depletion in patients with rheumatoid
arthritis (RA). Primary goals were to address both the immunohistologic and
potential toxic effects of this approach. Moreover, the correlation between
immunohistologic findings and clinical assessments of disease activity and
cartilage damage were assessed. METHODS: An open study was conducted in
consecutive RA patients who were scheduled for knee joint replacement in our
department. Synovial biopsy tissue was obtained from the knee joint at 2 weeks
before and at the time of surgery. This protocol was controlled for safety and
immunohistologic concordance in 6 patients. One week before surgery, 10 patients
received a single IA dose of clodronate liposomes. Staining of synovial tissue
for cell markers (CD68, CD14, CD3, CD38) and adhesion molecules (vascular cell
adhesion molecule 1 [VCAM-1], intercellular adhesion molecule 1 [ICAM-1]) was
assessed by 2 blinded observers. Local and systemic parameters of disease
activity were measured before each intervention. Cartilage damage was scored
using standard radiologic techniques at baseline and during surgery. RESULTS: A
single IA dose of clodronate liposomes significantly reduced the number of CD68
positive cells (P = 0.005) and the expression of ICAM-1 and VCAM-1 in the
synovial lining (P = 0.013 and P = 0.039, respectively). The intervention did not
affect fibroblast-like synoviocytes, T cells, or plasma cells. No
immunohistologic changes were observed in the control group. The procedure was
well tolerated. The levels of ICAM-1 and VCAM-1 in the sublining layers
correlated with the extent of macroscopic synovitis (P < 0.0005 and P < 0.005,
respectively). The expression of ICAM-1 and CD14 in the sublining correlated with
the levels of C-reactive protein (P < 0.0005 and P < 0.01, respectively).
Cartilage destruction was correlated only with the expression of CD68 in the
sublining (P = 0.02). CONCLUSION: A single IA administration of clodronate
liposomes leads to macrophage depletion and decreased expression of adhesion
molecules in the synovial lining in patients with longstanding RA. The procedure
is well tolerated, and its therapeutic potential is currently under
investigation. The expression of adhesion molecules in the sublining layers
reflects ongoing inflammation.
PMID- 11014345
TI - Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse
connective tissue diseases in children: a prospective multicenter study.
AB - OBJECTIVE: Osteopenia/osteoporosis is being increasingly reported as a
complication of many chronic diseases, even in children. In this preliminary
study, we evaluated the effect of an oral bisphosphonate (alendronate) on bone
mass in children with diffuse connective tissue diseases. METHODS: Thirty-eight
children with low bone mass were treated with alendronate for 1 year; 38 children
who had the same primary disorders as the study patients but in a less severe
form served as untreated control patients. We were also able to evaluate changes
in bone mass (before and after alendronate) in 16 of the treated patients whose
bone mineral density (BMD) had been routinely measured before the present study
was initiated. RESULTS: BMD increased by a mean +/- SD of 14.9 +/- 9.8% (P <
0.002 versus baseline) in the treated patients (reaching the normal range in 13
patients), while the BMD was 2.6 +/- 5% (not significant versus baseline) in the
control group (15 had a decrease). Most interestingly, there was a large increase
in BMD (15.3 +/-9.9%) after alendronate therapy in the 16 children who had their
BMD followed up in the year before the study, during which time they had shown
little increase in BMD (1.03 +/- 6.3%), and often a decrease. Considering their
condition, increases in the height of all patients was satisfactory. No new
fractures were observed after alendronate therapy was initiated. CONCLUSION:
Bisphosphonates can be considered essential components of the treatment of
secondary osteoporosis, not only in adults, but also in pediatric patients.
Alendronate has a positive effect on secondary osteopenia/osteoporosis in
children with connective tissue diseases.
PMID- 11014346
TI - Should postmenopausal women with rheumatoid arthritis who are starting
corticosteroid treatment be screened for osteoporosis? A cost-effectiveness
analysis.
AB - OBJECTIVE: To evaluate the cost-effectiveness of different strategies for
preventing corticosteroid-induced osteoporosis. METHODS: Simulated cohorts of
postmenopausal women with rheumatoid arthritis (RA) starting corticosteroid
treatment were examined. A Markov decision analysis model was developed to
compare different management strategies, including watchful waiting, screen and
treat, and empirical treatment. Treatment thresholds for the screen and treat
strategy were varied from bone mineral density (BMD) T scores <-1.0 to BMD T
scores <-4.0. RESULTS: Compared with a watchful waiting approach, the incremental
cost-effectiveness ratio for a strategy of screen and treat with alendronate at a
BMD T score of <-1.0 was $92,600 per quality-adjusted life year (QALY) gained.
This result was sensitive to the cost and efficacy of osteoporosis therapy and,
importantly, to the treatment threshold. At a treatment threshold of a BMD T
score <-2.5, the incremental cost-effectiveness ratio of screening and treating
was $76,100 per QALY. None of these results differed substantially for women
taking estrogen replacement therapy. CONCLUSION: The incremental cost
effectiveness ratio of a strategy of screening and treating postmenopausal female
RA patients with BMD T scores of < -1.0, compared with watchful waiting, was
greater than that of other well-accepted medical interventions. The cost
effectiveness ratios were more acceptable when a T score treatment threshold of <
2.5 was used. These conclusions are limited by the lack of data on fracture and
treatment efficacy in corticosteroid-treated patients.
PMID- 11014347
TI - Interleukin-10 blockade corrects impaired in vitro cellular immune responses of
systemic lupus erythematosus patients.
AB - OBJECTIVE: Many systemic lupus erythematosus (SLE) patients display impaired
cellular immune responses against allo- or recall antigens. Given the down
regulating properties of interleukin-10 (IL-10) on antigen-presenting cell
functions, this study was undertaken to investigate whether the well-known
overproduction of IL-10 by SLE peripheral blood mononuclear cells (PBMC) was
involved in this process. METHODS: We measured the proliferation of SLE or
control PBMC against irradiated allogeneic dendritic cells in the absence or
presence of antibodies blocking IL-10 activity, or in the absence or presence of
IL-12. RESULTS: As a group, SLE PBMC proliferated against allogeneic targets less
than control PBMC. However, SLE patients could be categorized as good responders
or poor responders according to the amplitude of their allogeneic response.
Interestingly, serum IL-10 concentrations were significantly higher in the poor
responders than in the good responders or in the controls, and addition of
antibodies blocking IL-10 activity significantly increased the proliferative
responses of the group. We confirmed the role of IL-10 in the impaired allogeneic
responses displayed by SLE PBMC by demonstrating that addition of IL-10
containing SLE PBMC supernatants inhibited a normal allogeneic response between
unrelated healthy controls, and by showing that this inhibitory effect was
commensurate with the concentrations of IL-10 measured in the supernatants. In
this experimental setting, we also demonstrated that IL-10-containing SLE PBMC
supernatants inhibited IL-12 p35 and IL-12 p40 gene expression. Consistent with
the last observation, we found that addition of exogenous IL-12 restored the
proliferation of poor-responder SLE patients' PBMC. CONCLUSION: Taken together,
these results indicate that dysregulation of the IL-10/IL-12 balance plays a
critical role in the impaired cellular immune responses observed in SLE patients.
PMID- 11014348
TI - Association of autoantibodies against the phosphatidylserine-prothrombin complex
with manifestations of the antiphospholipid syndrome and with the presence of
lupus anticoagulant.
AB - OBJECTIVE: To clarify the association of autoantibodies against prothrombin with
the clinical manifestations of the antiphospholipid syndrome (APS) and with the
presence of lupus anticoagulant (LAC). METHODS: We examined 265 patients who
visited our autoimmune disease clinic. IgG and IgM antiprothrombin antibodies
were tested by enzyme-linked immunosorbent assay (ELISA) as either
antiphosphatidylserine-prothrombin complex (aPS/PT) antibodies or as antibodies
against prothrombin coated on irradiated ELISA plates (as antigen) (aPT). IgG,
IgM, and IgA anticardiolipin (aCL) antibodies and their beta2-glycoprotein I
(beta2GPI) dependency were also evaluated by ELISA. LAC was tested by 3 different
methods. RESULTS: The presence of aPS/PT, but not of aPT, significantly
correlated with the clinical manifestations of APS (odds ratio [OR] 4.39, 95%
confidence interval [95% CI] 2.06-9.38), and aPS/PT antibodies were as specific
as beta2GPI-dependent aCL for APS (93.1% for both). IgG aPS/PT strongly
correlated with the presence of LAC as detected using the dilute Russell viper
venom time test (OR 38.2, 95% CI 13.4-109.1). CONCLUSION: Antiprothrombin
antibodies are heterogeneous and their clinical relevance depends on the method
of detection applied. Positive results on the aPS/PT test can serve as a marker
of thrombotic events in patients with autoimmune diseases.
PMID- 11014349
TI - Chlorpromazine induces apoptosis in activated human lymphoblasts: a mechanism
supporting the induction of drug-induced lupus erythematosus?
AB - OBJECTIVE: Drug-induced lupus erythematosus is a serious side effect of certain
medications, such as procainamide, quinidine, hydralazine, chlorpromazine, and
isoniazid, the underlying pathogenesis of which is unresolved. In this study, we
examined the influence of these drugs on the regulation of apoptosis, or
programmed cell death, in quiescent and activated human lymphocytes. We also
discuss the dysregulation of apoptosis as a pathogenetic factor in systemic lupus
erythematosus. METHODS: Peripheral blood mononuclear cells or activated
lymphoblasts from normal donors were incubated with different concentrations of
each of the above-mentioned drugs. RESULTS: We did not find induction of
apoptosis in quiescent cells over a broad concentration range. In contrast,
lymphoblasts readily underwent apoptosis when cultured with chlorpromazine, but
not any of the other drugs, after stimulation with interleukin-2 (IL-2) in a dose
, time- and cell cycle-dependent manner. By several lines of evidence, toxicity
was ruled out. Characteristic features of apoptosis-like incorporation of
propidium iodide (PI), such as increased annexin V binding, changes in
mitochondrial membrane potential, and induction of DNA breaks (as evidenced by
TUNEL techniques), could be induced in lymphoblasts after chlorpromazine
treatment. Chlorpromazine did not cause apoptosis by inhibition of cytokine
binding or blockade of early intracellular signaling. The protease inhibitor Z
VAD and the ceramide inhibitor sphingosine 1-phosphate effectively blocked
chlorpromazine-induced apoptosis (by PI staining and by externalization of
phosphatidylserine), in contrast to the caspase 3/CPP32 inhibitor DEVD, which had
only minor effects. Western blot analysis revealed IL-2-mediated phosphorylation
of extracellular signal-regulated kinase, which was sensitive to chlorpromazine.
Using lymphoblasts from a patient with Canale-Smith syndrome, we found that
chlorpromazine-mediated apoptosis is Fas/ APO-1 independent. CONCLUSION: These
data suggest that chlorpromazine mediates apoptosis in human lymphoblasts through
specific activation of intracellular proapoptotic signaling cascades. This
mechanism might lead to an unsynchronized inflow of apoptotic break-down products
and thereby to the induction of (auto)immunity against nuclear components.
PMID- 11014350
TI - HLA-DQA1*0501 is associated with diffuse systemic sclerosis in Caucasian men.
AB - OBJECTIVE: Systemic sclerosis (SSc) is uncommon in men, and relatively little is
known about factors contributing to its pathogenesis in this population. In the
current study, we investigated HLA class II alleles in men with SSc. We also
investigated the hypothesis that HLA compatibility of the mother could be a risk
factor for SSc in men. METHODS: Sequence-specific oligonucleotide probe typing
was used to determine DQA1, DQB1, and DRB1 alleles of SSc patients (50 men and 36
parous women), healthy controls (59 men and 80 parous women), 26 mothers of men
with SSc, and 44 mothers of healthy men. All study subjects were Caucasian, and
allele frequencies were compared with those of Caucasian controls from the
Eleventh International Histocompatibility Workshop as well as those of local
controls. RESULTS: The DQA1*0501 allele was significantly increased among men
with SSc compared with healthy men (odds ratio [OR] 2.3, P = 0.006, Pcorr =
0.04). DQA1*0501 was associated with diffuse SSc in men (OR 3.0, P = 0.004, Pcorr
= 0.03), but not with limited SSc in men. Maternal HLA compatibility was not a
risk factor for SSc in men. CONCLUSION: Previous studies have shown associations
of DRB1 alleles with SSc, but have rarely determined DQA1 allele frequencies. Our
findings indicate that a specific DQA1 allele is associated with SSc, and that
DRB1 associations may be due to linkage disequilibrium with DQA1. Moreover, by
analyzing genetic susceptibility according to sex, we found that the contribution
of HLA genes to the risk of SSc was substantially greater in men than in parous
women.
PMID- 11014351
TI - Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not
merely enthesitis.
AB - OBJECTIVE: To systematically study the histopathology of sacroiliitis in
ankylosing spondylitis (AS) at 5 different stages of the disease. METHODS: Two
independent observers assessed 75 microscopic features in the sacroiliac (SI)
joints in 12 cases of AS (5 biopsies, 7 autopsies) and in 22 control cases (all
autopsies). RESULTS: In AS, synovitis, pannus formation, myxoid marrow,
superficial cartilage destruction, enthesitis, intraarticular fibrous strands,
new bone formation, and bony ankylosis were significantly more frequent than in
control cases, in which there was more endochondral bone within deep-zone
articular cartilage. Cartilaginous fusion occurred in both groups, but much
earlier in AS. There was no residual synovium when the joint lumen was totally
occluded. Mild but destructive synovitis and myxoid subchondral bone marrow were
the earliest changes identified in AS. These lesions destroyed the adjacent
articular tissues, a loss that was followed to varying degrees by fibrous
scarring, woven bone, and new cartilage. The original cartilages also fused, and
chondral fusion was the predominant mode of ankylosis. Both the original and the
reparative cartilaginous tissues were replaced by bone. Active enthesitis
occurred in 2 advanced and 3 late cases; fibrous scar tissue, presumed to
represent previous enthesitis, was observed in all stages except the earliest.
Paraarticular bone was at first dense, and later porotic. CONCLUSION: In the
sacroiliitis of AS, two findings predominate: 1) synovitis and subchondral bone
marrow changes offer a more rational explanation for widespread joint destruction
than does enthesitis; and 2) an unusual form of chondroid metaplasia contributes
to ankylosis.
PMID- 11014352
TI - Prediction of relapses in Wegener's granulomatosis by measurement of
antineutrophil cytoplasmic antibody levels: a prospective study.
AB - OBJECTIVE: Prediction of relapses in Wegener's granulomatosis (WG) by measuring
levels of antineutrophil cytoplasmic antibodies (ANCA) directed against
proteinase 3 (PR3) or myeloperoxidase (MPO) remains a controversial issue. To
assess the value of serial quantification of ANCA by indirect immunofluorescence
(IIF) and antigen-specific enzyme-linked immunosorbent assay (ELISA) for
monitoring disease activity in patients with WG, a prospective observational
study was conducted in patients with WG attending an outpatient clinic in the
Netherlands. METHODS: One hundred patients with WG (85 with PR3-ANCA, 15 with MPO
ANCA) were studied prospectively from 1996 to 1998. Serum samples were obtained
and analyzed every 2 months for ANCA levels. Disease activity was prospectively
assessed without knowledge of the ANCA levels. RESULTS: Relapses occurred in 37
of 100 patients (37%). Thirty-four (92%) of the 37 patients showed a rise in the
level of ANCA preceding their relapse, as detected by ELISA or IIF. The
predictive value of an increase in ANCA titers for relapse was 57% (17 of 30) for
cytoplasmic/classic ANCA (cANCA; by IIF), 71% (27 of 38) for PR3-ANCA (by ELISA),
and 100% (3 of 3) for MPO-ANCA (by ELISA). The predictive value of a rise in ANCA
as measured by ELISA or IIF did not substantially improve following concomitant
measurement of the IgG3 subclass of PR3-ANCA. Forty-three percent of patients who
showed a rise in cANCA (by IIF) and 29% with a rise in PR3-ANCA (by ELISA) did
not subsequently experience a relapse. CONCLUSION: Serial measurement of ANCA
levels is valuable for the early prediction of relapses in patients with WG.
PMID- 11014353
TI - An autosomal dominant periodic fever associated with AA amyloidosis in a north
Indian family maps to distal chromosome 1q.
AB - OBJECTIVE: To investigate genetic susceptibility in the first Indian family
identified as having an autosomal dominantly inherited periodic fever syndrome.
The inflammatory disease was characterized chiefly by arthralgia, skin rashes,
and AA amyloidosis. METHODS: Markers from known periodic fever susceptibility
loci were investigated in 7 affected and 11 healthy members of a north Indian
family. These included the TNFRSF1A locus (formerly known as TNFRI), which is
involved in autosomal dominant tumor necrosis factor receptor-associated periodic
syndrome on chromosome 12p13, the familial Mediterranean fever locus (MEFV) on
chromosome 16p13, the hyperimmunoglobulinemia D and periodic fever syndrome
(HIDS) locus on chromosome 12q24, and the Muckle-Wells syndrome/familial cold
urticaria (MWS/FCU) locus on distal chromosome 1q44. RESULTS: Linkage to both
TNFRSF1A and MEFV was definitively excluded, and DNA sequencing of these genes
revealed no mutations. Furthermore, there was no evidence of linkage to the HIDS
locus. In contrast, significant logarithm of odds scores for 5 markers from the
MWS/FCU region were obtained in this family, and the disease segregated with the
same haplotype in all affected members. CONCLUSION: We have identified an
inherited inflammatory disease in a north Indian family with clinical features
overlapping some of those of MWS and FCU. The susceptibility gene maps to distal
chromosome 1q44, a region already implicated in both MWS and FCU. Different
mutations in the same (or a closely related) gene may be responsible for an
inflammatory disease with a broad phenotype among diverse ethnic populations.
PMID- 11014354
TI - Localization of a gene for familial recurrent arthritis.
AB - OBJECTIVE: To localize the gene for familial recurrent arthritis via a genome
wide linkage scan in an extended kindred with the disease. METHODS: A 3
generation family in which 9 members were diagnosed with juvenile idiopathic
arthritis (JIA) was ascertained. In this family the disease was of very early
onset and included episodic inflammation leading to eventual destruction of
joints, muscle, and skin. We treated this disorder as a distinct clinical entity
that we have named "familial recurrent arthritis." A genome-wide linkage scan
with polymorphic microsatellites at 10-15-cM resolution was initiated. RESULTS:
The genome-wide scan generated a maximum 2-point logarithm of odds score with
D15S211 (Zmax = 3.27 at thetamax = 0.0010). Haplotype reconstruction defined a
candidate region of approximately 20 cM flanked proximally by D15S983 and
distally by D15S127 on human chromosome 15. CONCLUSION: A gene for familial
recurrent arthritis was localized to 15q22-24, as a result of a genome-wide
linkage scan in a large, multiply affected kindred. Identification of the altered
gene will provide insights into the pathogenesis of autoimmune joint destruction
that is reminiscent of JIA.
PMID- 11014355
TI - Clinical images: Neuropsychiatric systemic lupus erythematosus.
PMID- 11014356
TI - Mesenchymal cells expressing bone morphogenetic protein receptors are present in
the rheumatoid arthritis joint.
AB - OBJECTIVE: To evaluate the presence of cells of an early mesenchymal lineage, as
judged by the expression of bone morphogenetic protein receptors (BMPRs), in the
joints of normal individuals and patients with rheumatoid arthritis (RA).
METHODS: Synovial fluids, single cell suspensions of cultured fibroblast-like
synoviocytes (FLS), and synovial tissues were examined by immunohistology with
antibodies to BMPR type IA (BMPRIA), BMPRIB, and BMPRII and then quantified using
computerized image analysis. Other antibodies were evaluated by cytofluorography.
RESULTS: In primary cultures of joint effusions from patients with RA and other
forms of inflammatory arthritis, there were large adherent cells with the
appearance of either fibroblasts or stromal cells that stained with antibodies to
mesenchymal elements-CD44, type I collagen, alpha-actin, and vimentin-but not
with antibodies to hematopoietic markers. These cells proliferated rapidly,
expressed BMPRIA and BMPRII, and soon became the predominant cells in culture.
They were retained through multiple passages and persistently displayed surface
vascular cell adhesion molecule 1. Immunohistochemical analysis of cultured RA
FLS (passages 3, 4, and 6; n = 6) revealed that 11.6% were BMPR-positive, while
only 2.0% of osteoarthritis FLS (passage 4; n = 3) were BMPR-positive, and 1
normal synovial culture had no BMPR-positive cells. In all RA synovial membranes
examined (n = 9), BMPRI- and BMPRII-expressing cells were identified in the
intimal lining and were also scattered in the subintima. These cells constituted
approximately 25% and approximately 7% of the cells in each area, respectively.
Double immunostaining showed no coexpression of BMPR-positive cells with CD68,
CD34, or CD3. Cells expressing BMPR were not seen in any normal synovial samples
(n = 4). Strong staining for BMPR was identified on cells at the invasive front
of the pannus and at sites of cartilage erosion. CONCLUSION: The inflamed RA
joint contains BMPR-positive mesenchymal cells. Their origin is still
speculative, but since their counterparts in the bone marrow are essential for
osteoclastogenesis, support lymphocyte development and maturation, and protect T
cells and B cells from programmed cell death, the BMPR-positive cells may be
essential elements in the pathogenesis of RA and other inflammatory forms of
chronic synovitis.
PMID- 11014357
TI - Suppression of arthritis and protection from bone destruction by treatment with
TNP-470/AGM-1470 in a transgenic mouse model of rheumatoid arthritis.
AB - OBJECTIVE: We assessed the clinical and histologic features of angiogenesis
inhibition in a transgenic mouse model of arthritis that closely resembles
rheumatoid arthritis (RA) in humans. METHODS: KRN/NOD mice, which spontaneously
develop arthritis, were treated with TNP-470, an angiogenesis inhibitor. Disease
was monitored by use of clinical indices and histologic examinations; circulating
blood levels of vascular endothelial growth factor were determined by enzyme
linked immunosorbent assay. RESULTS: In the preventive protocol, with TNP-470
administration at a dosage of 60 mg/kg of body weight, the onset of arthritis was
delayed and its clinical intensity was rather mild; 100% of placebo-treated
transgenic mice developed arthritis that led to severe articular destruction. At
a dosage of 90 mg/kg of TNP-470, the appearance of clinical signs was delayed for
a longer period of time and disease was almost abolished. The therapeutic regimen
alleviated clinical signs only when given during the very early stage of disease.
Reductions in cartilage and bone destruction by TNP-470 treatment were observed
histologically, a feature that was still evident at 30 and 80 days after
injections were withdrawn. CONCLUSION: Our demonstration that in vivo
administration of an angiogenesis inhibitor suppresses arthritis and protects
from bone destruction provides new insight into the pathogenesis of the disease
and opens new possibilities in the treatment of RA in humans.
PMID- 11014358
TI - Suppression of streptococcal cell wall-induced arthritis by human chorionic
gonadotropin.
AB - OBJECTIVE: To determine whether human chorionic gonadotropin (HCG) contributes to
pregnancy-associated immunosuppression, as observed clinically by an amelioration
of symptoms in human autoimmune diseases, including rheumatoid arthritis, during
pregnancy. METHODS: Administration of HCG was initiated 2 days prior to an
arthritogenic dose of streptococcal cell wall (SCW) in nonpregnant female rats,
and the development and severity of SCW-induced arthritis was monitored.
Inflammatory mediators, including plasma nitrite/nitrate and cytokine levels,
were measured. Inducible nitric oxide synthase (iNOS) protein and cytokine
messenger RNA expression in joint tissue were compared between treated and
untreated arthritic animals. RESULTS: Systemic administration of HCG resulted in
a dose-dependent reduction in the clinical arthritis index. Consistent with the
amelioration of clinical symptoms, HCG significantly reduced the inflammatory
cell infiltration, pannus formation, and bone and cartilage degradation.
Mechanistically, HCG therapy was associated with suppression of the overzealous
production of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-1beta,
which contribute to synovial pathology in animals with SCW-induced arthritis.
Circulating nitric oxide and the amount of iNOS protein were also reduced.
Furthermore, circulating transforming growth factor beta levels were elevated by
the HCG, all of which suggest monocytes/macrophages as a potential target.
CONCLUSION: These findings indicate that HCG exerts a protective effect in this
experimental arthritis model, through modulation of inflammatory mediators.
PMID- 11014359
TI - The effects of local administration of lactoferrin on inflammation in murine
autoimmune and infectious arthritis.
AB - OBJECTIVE: To determine whether lactoferrin can modify articular inflammation in
murine models of autoimmune and septic arthritis. METHODS: Collagen arthritis was
induced in DBA/1 mice and Staphylococcus aureus septic arthritis in Swiss mice.
Joints with established inflammation were injected periarticularly with 0.5 mg or
1 mg of human lactoferrin, and arthritis was monitored for 3 days. RESULTS: DBA/1
mice injected with lactoferrin showed significantly suppressed local inflammation
for up to 3 days, achieving up to 71% of the effect of corticosteroid.
Periarticular injection of 125I-lactoferrin confirmed that 25% of lactoferrin was
retained in paws after 6 hours. Serum levels of interleukin-6, however, were not
significantly reduced, suggesting a predominantly local antiinflammatory effect.
Similarly, local, periarticular administration of lactoferrin into S aureus
infected Swiss mice significantly suppressed paw inflammation and did not enhance
bacterial survival. CONCLUSION: Lactoferrin may have clinical utility in reducing
articular inflammation, particularly in septic arthritis, in which
antiinflammatory effects may be achieved without promoting bacterial survival.
PMID- 11014360
TI - Functional estrogen receptors in adult articular cartilage: estrogen replacement
therapy increases chondrocyte synthesis of proteoglycans and insulin-like growth
factor binding protein 2.
AB - OBJECTIVE: Epidemiologic studies suggest a protective effect of estrogen
replacement therapy (ERT) against the development of knee and hip osteoarthritis,
but a potential mechanism for this effect is not known. The present study was
done to determine if functional estrogen receptors (ERs) are present in adult
articular cartilage and to determine if ERT in vivo affects the production of
insulin-like growth factor binding proteins (IGFBPs). METHODS: Reverse
transcription-polymerase chain reaction, immunoblotting, and immunohistochemistry
were used to measure messenger RNA (mRNA) and protein for ERs in adult monkey
articular cartilage. Cultured chondrocytes transfected with a reporter construct
containing the estrogen response element (ERE/luciferase) were stimulated with
estrogen in vitro to determine functional activity of the ERs. IGFBP production
was measured by ligand and immunoblotting of conditioned media of cells cultured
from control and estrogen-treated surgically menopausal monkeys. Proteoglycan
(PG) synthesis was estimated by measurement of 35SO4 incorporation. RESULTS: ERa
and ERbeta mRNA were present in adult monkey articular cartilage, and ER protein
was demonstrated by immunoblotting and immunohistochemistry. Estrogen treatment
in vitro of cells transfected with the ERE/luciferase construct resulted in a
2.87-fold increase (P = 0.0163) in reporter production over that of untreated
cells. Compared with untreated controls, IGFBP-2 production was significantly
increased (P < 0.008) in conditioned media of chondrocytes cultured from monkeys
that had received ERT in vivo. Increased IGFBP-2 in these cultures was associated
with a 1.41-fold increase (P = 0.02) in the level of sulfate incorporation.
CONCLUSION: Transcriptionally functional ER are present in adult articular
cartilage, and ERT increases the production of IGFBP-2 and the synthesis of PGs
by chondrocytes from surgically menopausal monkeys. These results indicate that
estrogen can have a direct effect on adult articular cartilage.
PMID- 11014361
TI - Mechanotransduction via integrins and interleukin-4 results in altered aggrecan
and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic,
human articular chondrocytes.
AB - OBJECTIVE: To determine molecular events in the regulation of messenger RNA
(mRNA) of cartilage matrix molecules and proteases by mechanical stimulation of
chondrocytes from normal human articular cartilage and to ascertain whether
similar regulatory systems are present in chondrocytes from osteoarthritic (OA)
cartilage. METHODS: Chondrocytes extracted from macroscopically and
microscopically normal and OA cartilage were mechanically stimulated in the
presence or absence of GRGDSP or GRADSP oligopeptides, neutralizing interleukin-4
(IL-4) antibodies, gadolinium, or apamin. The relative levels of mRNA for
aggrecan, tenascin, matrix metalloproteinase 1 (MMP-1), MMP-3, and tissue
inhibitor of metalloproteinases 1 (TIMP-1) were determined by semiquantitative
reverse transcription-polymerase chain reaction at several time points up to 24
hours poststimulation, using GAPDH as a control. RESULTS: Normal chondrocytes
showed an increase in aggrecan mRNA and a decrease in MMP-3 mRNA within 1 hour
following stimulation, with a return to baseline levels within 24 hours. These
changes were blocked by GRGDSP, IL-4 antibodies, and gadolinium, but were
unaffected by apamin. In contrast, chondrocytes isolated from OA cartilage showed
no change in aggrecan or MMP-3 mRNA levels following mechanical stimulation. The
mRNA levels of tenascin, MMP-1, and TIMP-1 were unaltered in mechanically
stimulated normal and OA chondrocytes. CONCLUSION: Mechanical stimulation of
human articular chondrocytes in vitro results in increased levels of aggrecan
mRNA and decreased levels of MMP-3 mRNA. The transduction process involves
integrins, stretch-activated ion channels, and IL-4. This chondroprotective
response is absent in chondrocytes from OA cartilage. Abnormalities of
mechanotransduction leading to aberrant chondrocyte activity in diseased
articular cartilage may be important in the progression of OA.
PMID- 11014362
TI - Modulation of collagenase 3 in human osteoarthritic cartilage by activation of
extracellular transforming growth factor beta: role of furin convertase.
AB - OBJECTIVE: Treatment of normal cartilage with transforming growth factor beta
(TGFbeta) can increase the synthesis of collagenase 3 by chondrocytes and mimic
the in situ distribution of this enzyme in osteoarthritic (OA) cartilage, which
occurs predominantly in the deep zone. In this study, we examined the elements of
the TGFbeta system that are potentially relevant to this effect. METHODS:
TGFbeta1 and TGFbeta2 levels in cultured cartilage explants were determined by
enzyme-linked immunosorbent assay (ELISA). OA cartilage explants were treated
with small latent TGFbeta1 complex in the presence of various inhibitors, and
collagenase 3 levels were determined by ELISA. The inhibitors were against serine
proteases, plasmin, cathepsins, furin, and a neutralizing antibody against the
mannose-6 phosphate/ insulin-like growth factor 2 receptor (M6P/IGF-2R). Small
latent TGFbeta1, TGFbeta receptor types I, II, and III (TGFbetaRI, RII, and
RIII), M6P/IGF-2R, and furin were immunolocalized in cartilage. RESULTS: Our data
showed that latent TGFbeta1 is the major isoform that is synthesized; levels of
17.2 +/-1.7 pg/mg and 1.1 +/- 0.3 pg/mg tissue wet weight (mean +/- SEM) were
found for total TGFbeta1 and TGFbeta2, respectively, in OA cartilage. A general
serine protease inhibitor abrogated activation of both endogenous and exogenous
small latent TGFbeta1. Plasmin and furin inhibitors and anti-M6P/IGF-2R reduced
the levels of exogenous small latent TGFbeta1 complex-induced collagenase 3 by
33%, 95%, and 76%, respectively, but the cathepsin inhibitor had no effect.
Immunolocalization of the small latent TGFbeta1 complex as well as of TGFbetaRI
and RII revealed a statistically significant increase in the chondrocyte score in
only the deep zone of OA cartilage. The M6P/IGF-2R level was significantly higher
in OA cartilage in both the superficial and deep zones. Furin was found in normal
cartilage exclusively in the superficial zone, whereas in OA cartilage, a level
similar to that in normal cartilage was found in the superficial zone, but a
significantly higher cell score (mean +/- SEM 23.6 +/- 4.7%) was registered in
the deep zone. CONCLUSION: The mechanisms of TGFbeta activation/ activity with
regard to collagenase 3 modulation in cartilage appear to be controlled by furin
convertase with or without M6P/IGF-2R. These factors and the small latent TGFbeta
complex are increased in the deep zone of OA cartilage, corresponding to the
preferential site of collagenase 3 production.
PMID- 11014363
TI - Reduction in the chondrocyte response to insulin-like growth factor 1 in aging
and osteoarthritis: studies in a non-human primate model of naturally occurring
disease.
AB - OBJECTIVE: Although the development of osteoarthritis (OA) is closely associated
with aging, the mechanism for this association is not clear. This study was
designed to determine the effects of aging and OA on the chondrocyte response to
stimulation with insulin-like growth factor 1 (IGF-1) in a non-human primate
model of naturally occurring OA. METHODS: Chondrocytes were isolated from
cartilage removed separately from the medial and lateral femoral condyles and
tibial plateaus of cynomolgus monkeys at the time of necropsy. Each joint site
was scored histologically on a scale of 0-7 for OA pathologic changes. Isolated
chondrocytes were cultured in alginate in serum-free medium and stimulated with
IGF-1 or des(1-3) IGF-1, which has a much lower affinity for IGF binding proteins
(IGFBP) than IGF-1. Response was measured as the ability to stimulate sulfate and
proline incorporation. RESULTS: Cartilage samples from 34 monkeys ranging in age
from 6.7 years to 27 years and with histologic scores ranging from 0 to 7 were
analyzed. A significant decline in the response to IGF-1 was noted with both
increasing age and increasing OA score. Controlling for the OA score, the
estimated effect of age on IGF-1 response, measured by total sulfate
incorporation, was a decline of 3.81% per year (P = 0.0001), or a 75% decline
over 20 years as a monkey ages from young to older adult. Controlling for age,
the effect of OA score was significant only for proline incorporation in the
alginate matrix (estimated slope coefficient +/-standard error -15.9 +/- 7.2; P =
0.03), suggesting a negative effect of OA on retention of 3H-proline-labeled
proteins in the matrix. There was a significantly reduced response to des(1-3)
IGF-1 with increasing age, but no effect of OA score on response to des(1-3) IGF
1. There was no effect of age on cell viability. CONCLUSION: These results
demonstrate a significant age-related decline in the chondrocyte response to IGF
1. The finding that increasing OA score was associated with a reduced response to
intact IGF-1 but not des(1-3) IGF-1 suggests a role of increased production of
inhibitory IGFBP in OA. Since the cells from older animals had a reduced response
to both forms of IGF-1, the mechanism of the reduced response with age cannot be
attributed to changes in IGFBP. Age-related changes in IGF receptors or, more
likely, age-related alterations in intracellular signal transduction may also be
involved.
PMID- 11014364
TI - Differences in type II collagen degradation between peripheral and central
cartilage of rat stifle joints after cranial cruciate ligament transection.
AB - OBJECTIVE: Type II collagen degradation is thought to be the key process in
cartilage degradation during the development of osteoarthritis (OA). In this
study, we investigated the kinetics of type II collagen degradation during
surgically induced OA. METHODS: Experimental OA was induced in male Wistar rats
by transecting the cranial (anterior) cruciate ligament (CCL). Hematoxylin and
eosin staining was used to study overall cartilage degradation, while
immunostained sections were used to demonstrate denatured type II collagen (Col2
3/4m antibody) and the collagenase cleavage site in type II collagen (Col2-3/
4Cshort antibody). RESULTS: During the first 3-4 weeks, cartilage destruction,
associated with chondrocyte death, proteoglycan depletion, and a marked increase
in the collagenase cleavage neoepitope, was mainly located at the margins of the
cartilage. From weeks 3-4, the central part of the cartilage showed increased
surface fibrillation and apparent chondrocyte death. In these areas, increased
denatured type II collagen staining but little cleavage-site staining was
present. CONCLUSION: These results indicate that cartilage degradation after CCL
transection in the rat consists of 2 phases. An early phase located at the
cartilage margins and a late phase located at the central part of the cartilage.
In the early phase, collagenase-dependent cartilage damage occurred. During the
late phase, the level of type II collagen denaturation increased.
PMID- 11014365
TI - Analysis of autoimmune bone marrow by antibody-phage display: somatic mutations
and third complementarity-determining region arginines in anti-DNA gamma and
kappa V genes.
AB - OBJECTIVE: To examine anti-double-stranded DNA (anti-dsDNA) IgG autoantibodies
from the bone marrow of individuals with systemic lupus erythematosus (SLE).
METHODS: A library of single-chain variable fragments (scFv) was constructed from
SLE bone marrow complementary DNA of gamma, kappa, and lambda isotype by cloning
into the pHENIX phagemid vector. The library was screened with dsDNA in solution,
and 2 anti-DNA phage, DNA1 and DNA4, were isolated and their Ig V genes
sequenced. Soluble scFv corresponding to DNA1 and DNA4, and their heavy (H)- and
light (L)-chain recombinants, were prepared, purified, and analyzed for binding
to DNA by enzyme-linked immunosorbent assay. RESULTS: DNA1 and DNA4 used
different Ig H-chain (3-30 and 5-51, respectively) and L-chain (DPK15 and DPK22,
respectively) V genes. The ratios of replacement mutations to silent mutations in
DNA1 and DNA4 suggest that their V genes were selected for improved antigen
binding in vivo. The recombinant between DNA4VH and DNA1VL showed the highest
relative affinity for both single-stranded DNA and dsDNA. These 2 Ig subunits
contained third complementarity-determining region arginines and had acquired the
majority of replacement mutations. CONCLUSION: Anti-dsDNA IgG autoantibodies from
the bone marrow of SLE patients exploit diverse V genes and cationic V-D-J and V
J junctions for DNA binding, and accumulate replacement mutations that enhance
binding.
PMID- 11014366
TI - Sjogren's syndrome occurring after hepatitis B vaccination.
PMID- 11014367
TI - Apolipoprotein(a) deposition in atherosclerotic coronary arteries of a patient
with systemic lupus erythematosus: comment on the article by Romero et al.
PMID- 11014368
TI - Presentation of the Southern Society for Clinical Investigation Founders Medal to
Dr. Martin Steinberg.
PMID- 11014369
TI - Southern Society for Clinical Investigation Founders Medal recipient's address.
PMID- 11014370
TI - Regional hemodynamics after chronic nitric oxide inhibition in spontaneously
hypertensive rats.
AB - BACKGROUND: Inhibition of nitric oxide (NO) synthase by L-arginine analogs is
associated with elevation of blood pressure in rats. Because endothelium
dependent vasomotion in different vascular beds is not homogenous, the aim of
this study was to characterize and compare regional hemodynamic responses in
carotid, femoral, and renal vascular beds after chronic NO inhibition in
spontaneously hypertensive rats. The possible role of circulating endothelin and
renin angiotensin systems in mediating the effects of chronic NO inhibition was
also studied. METHODS: Systemic and regional hemodynamics, left ventricular mass,
plasma renin activity, and plasma endothelin-1 were determined in control and
Nomega-nitro-Larginine methyl ester (L-NAME)-treated (10 mg/kg/day, 4 weeks)
spontaneously hypertensive rats. RESULTS: L-NAME treatment increased arterial
pressure and total peripheral and regional vascular resistance and decreased
cardiac output, stroke volume, and regional blood flow. An increase in blood flow
ratio and a decrease in vascular resistance ratio between carotid and renal as
well as femoral and renal vascular beds in rats treated with L-NAME was found.
Blood flow and vascular resistance ratios between femoral and carotid vascular
beds remained unchanged. L-NAME increased plasma renin activity and left
ventricular weight/body weight ratio, whereas plasma endothelin-1 was not
modified. CONCLUSIONS: The results of this study showed that the renal
circulation seemed to be more sensitive to the effects of chronic NO inhibition
than carotid and femoral vascular beds. Simultaneous activation of the renin
angiotensin system may further potentiate cardiovascular effects of chronic NO
inhibition. No evidence that circulating endothelin-1 plays a role in this model
of hypertension was found.
PMID- 11014371
TI - Increased leukocyte aggregation induced by gamma-globulin: a clue to the presence
of pseudoleukopenia.
AB - BACKGROUND: Previous articles have reported the appearance of leukopenia after
the administration of high-dose intravenous gamma-globulins. METHODS: A simple
slide test was used to reveal the state of leukocyte aggregation (LA) in the
peripheral blood as well as the absolute number of leukocytes in the slides.
RESULTS: A significant (P < 0.00001) increment was noted in the state of LA, from
9 +/- 6% before to 25 +/- 11% after gamma-globulin administration. This was
accompanied by a significant (P < 0.0004) reduction in the number of white blood
cells in the peripheral blood (from 8433 +/- 3905 to 6550 +/- 3252 cells/mm3) but
no significant change in the absolute number of the cells as determined by the
leukocyte count per high power field in the peripheral slides. CONCLUSIONS: We
raise the possibility that the leukopenia reported in some patients after the
intravenous administration of high dose gamma-globulin is explained in part by
the agglutination effect of the drug.
PMID- 11014372
TI - Serum level of soluble tumor necrosis factor receptor II (sTNF-R75) is apparently
an index of overall monocyte-related infectious and inflammatory activity.
AB - BACKGROUND: The serum level of soluble tumor necrosis factor receptor II (sTNF
R75) has been recently found to correlate with the activity and/or severity of
several different infectious and inflammatory diseases. These results have led us
to presume that the serum sTNF-R75 level reflects the active immune activity of
all causes and may correlate well with nonspecific infectious and inflammatory
markers such as peripheral leukocyte counts and serum C-reactive protein level.
METHODS: In total, 110 apparently healthy adults, 55 men and 55 women, were
enrolled in the study. Serum levels of sTNF-R75, C-reactive protein, globulin,
alkaline phosphatase, lactate dehydrogenase, creatinine, urea nitrogen, and
counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils were
checked. The relationships between the serum sTNF-R75 level and other parameters
were analyzed using the SAS statistical program. RESULTS: By various statistical
methods, the serum sTNF-R75 level showed consistently significant positive links
with peripheral monocyte count, serum C-reactive protein level, and two
parameters of renal clearance function (serum urea nitrogen and creatinine
levels). Serum levels of alkaline phosphatase and lactate dehydrogenase had
significant positive links with the serum sTNF-R75 level by multivariate
regression analysis. There was no significant link between the serum sTNF-R75
level and counts of neutrophils, lymphocytes, eosinophils, or basophils.
CONCLUSIONS: Our results, together with those of recent reports showing positive
correlations between the serum sTNF-R75 level and activities/severities of
different infectious and inflammatory diseases, and also that TNF-alpha is
principally produced by monocytes and macrophages, suggest that the serum sTNF
R75 level is very probably an index of overall monocyte-related infectious and
inflammatory activities.
PMID- 11014373
TI - Proteinuria: potential causes and approach to evaluation.
AB - Proteinuria may be associated with a renal or systemic disease, or it may be
isolated. The latter occurs in asymptomatic patients without evidence of any
disease or abnormality of the urine sediment. Isolated proteinuria may be
subdivided into two broad groups: (1) benign forms, with a favorable-to-excellent
prognosis and (2) persistent forms, some of which have a worrisome prognosis.
Functional proteinuria may occur in disorders with altered renal hemodynamics,
usually resolves, and is not associated with progressive renal disease.
Idiopathic transient proteinuria is typically discovered on routine screening and
usually disappears on subsequent testing. In idiopathic intermittent proteinuria,
a significant number (50%) of urine samples exhibit abnormal rates of protein
excretion. Although structural abnormalities may be observed on renal biopsy,
progressive renal insufficiency is unusual. In orthostatic proteinuria, the rate
of protein excretion completely normalizes in the recumbent position. Long-term
studies show this to be a benign condition. In persistent isolated proteinuria,
at least 80% of random urine samples exhibit abnormal protein excretion. This
represents a heterogeneous group, but a significant proportion of these patients
have prominent renal pathologic findings and progress to serious renal disease.
Proteinuria with significant renal disease may be non-nephrotic or nephrotic
range. The former does not exclude glomerular disease, but tubulointerstitial or
vascular disorders are also likely when proteinuria is less than 2 g/24 hours.
Patients with nephrotic-range proteinuria generally have a glomerular disorder.
Distinction between benign and more ominous forms of proteinuria requires careful
evaluation.
PMID- 11014374
TI - A 65-year-old man with chronic back pain and shortness of breath.
PMID- 11014375
TI - Vasodilator therapy for chronic aortic and mitral regurgitation.
AB - The use of vasodilator therapy in chronic AR and MR may be beneficial in selected
patients and harmful in others. The hemodynamics of the two conditions are
different and must be taken into account. In AR, vasodilators reduce afterload
mismatch and can preserve LV function and delay the need for surgery. However, if
the patient has severely reduced diastolic blood pressure, vasodilators could
potentially impair coronary perfusion. In MR, vasodilators may reduce regurgitant
volume and LV preload depending on the mechanism of MR. In patients with MR
caused by dilated cardiomyopathy, vasodilators reduce symptoms, and improve
functional class. However, in mitral valve prolapse or hypertrophic
cardiomyopathy, vasodilators may worsen the MR and should be avoided. In other
primary causes of MR, vasodilators could potentially mask the development of LV
dysfunction and lead to unnecessary and harmful delays in surgery.
PMID- 11014376
TI - Focal bacterial nephritis (lobar nephronia) presenting as renal mass.
AB - A focal infection of the kidney can cause a diagnostic dilemma by mimicking a
neoplasm. We describe a case of focal bacterial nephritis (acute lobar nephronia)
caused by Escherichia coli in which the diagnosis was confirmed only after
surgical exploration. Although the patient had fever on admission, urine and
blood cultures were negative and fine needle aspiration of the kidney could not
rule out a well-differentiated carcinoma.
PMID- 11014377
TI - Hereditary angioedema precipitated by estrogen replacement therapy in a
menopausal woman.
AB - We report the first documented case in the literature of hereditary angioedema
presenting after commencement of estrogen replacement therapy for menopausal
symptoms. The late presentation of the disease and the precipitation of attacks
by physiological doses of estrogen replacement therapy make this a highly unusual
case. The pathophysiology of hereditary angioedema and its hormonal links are
discussed.
PMID- 11014378
TI - A subtherapeutic international normalized ratio despite increasing doses of
warfarin: could this be malabsorption?
AB - OBJECTIVE: To describe a case of warfarin resistance apparently caused by
malabsorption and to review the literature regarding warfarin resistance. CASE
SUMMARY: A 28-year-old renal transplant patient with systemic lupus erythematosus
was admitted for upper extremity thrombophlebitis. Resistance to oral warfarin
was demonstrated. Potential causes were investigated. The trapezoidal rule was
used to compare the area under the curve for intravenous versus oral dosing of
warfarin. The usual bioavailability of warfarin should be 100%. In this patient,
warfarin bioavailability after oral dosing was 1.5%. Three potential causes,
malabsorption (FF), enzymatic degradation (FG), and first-pass extraction in the
portal circulation (FH), are discussed. CONCLUSION: This case demonstrates
resistance to warfarin presumably caused by malabsorption.
PMID- 11014379
TI - Respiratory bronchiolitis: an unusual cause of pulmonary infiltrates in a
pregnant woman.
AB - Numerous mechanical, biochemical, and immunologic changes occur during pregnancy.
Because of these changes, pregnant women are more susceptible to infection,
thromboembolic disease, exacerbation of underlying immunologic disease, and heart
failure than women who are not pregnant. The differential diagnosis of diffuse
pulmonary infiltrates in a pregnant woman is broad; thus, the work-up can be very
challenging. If the patient fails to respond to conservative measures, such as
antibiotics, the cause of the infiltrate must be aggressively evaluated because
the treatment may be essential for the survival of the mother and fetus. We
report a case of a pregnant woman who presented with diffuse bilateral
infiltrates. After video-assisted thoracoscopic lung biopsy, this patient was
found to have respiratory bronchiolitis, a disease not previously reported during
pregnancy. Treatment with glucocorticoids resulted in a prompt improvement in
symptoms.
PMID- 11014380
TI - Nitric oxide decreases insulin resistance induced by high-fructose feeding.
AB - The effect of nitric oxide (NO) on insulin resistance was studied in high
fructose-fed rats. A sequential hyperinsulinemic euglycemic clamp procedure was
employed (insulin infusion rates: 3 and 30 mU/kg BW/min) in 12 high-fructose-fed
rats and 12 chow-fed rats while awake. Half of the high-fructose-fed and the chow
fed rats, respectively, were continuously given sodium nitroprusside (SNP, 3
ng/kg BW/min) during the clamp study. Blood glucose was clamped at the fasting
level in each rat. Plasma insulin levels during the 3 and 30 mU/kg BW/min insulin
infusions were 30 and 400 microU/ml, respectively. Metabolic clearance rate of
glucose (MCR) was regarded as an index of whole body insulin action. At both 3
and 30 mU/kg BW/min insulin infusions, high-fructose feeding showed a significant
decrease in MCR compared with the chow-fed rats. However, decreased MCRs were
stimulated by SNP administration and reached similar levels as the chow-fed rats.
SNP infusion did not influence MCRs in the chow-fed rats. Therefore it could be
concluded that NO can improve insulin resistance induced by high-fructose
feeding.
PMID- 11014381
TI - Expression of apolipoprotein B-100 in isolated human small intestine epithelium.
AB - Apolipoprotein B-48 (apoB48) is synthesized in the small intestine and becomes a
component of chylomicrons (CM). Apolipoprotein B-100 (apoB100) is synthesized in
liver and becomes a component of both very low density lipoprotein (VLDL) and low
density lipoprotein (LDL). To evaluate whether apoB100 is present in the human
small intestine, we performed immunohistochemical staining using anti-apoB100
monoclonal antibody (mAb). Jejunal samples stained positive and the granular
staining was noted in the supranuclear region of epithelial cells. We also
identified apoB100 expression in the epithelial cells by immunoblotting and dot
blotting of PCR-amplified cDNA. In order to exclude submucosal stroma
contaminated with blood, we used isolated epithelium from human small intestine
obtained by a crypt isolation technique. The results indicate that not only
apoB48, but also apoB100 are expressed in human small intestine epithelium. The
expression of apoB100 suggests that the dietary VLDL may be synthesized in human
small intestine epithelium and converted into LDL, which might play an important
role in atherosclerosis.
PMID- 11014382
TI - Interleukin-1 potentiates basal and AVP-stimulated ACTH secretion in vitro--the
role of CRH pre-incubation.
AB - The acute-phase cytokine interleukin-1 (IL-1) is known to activate the
hypothalamic pituitary adrenal axis, primarily via corticotropin releasing
hormone (CRH). The aim of this study was to determine whether IL-1beta could
directly stimulate ACTH secretion from perifused equine anterior pituitary cells,
and whether CRH pre-incubation affected corticotroph responsiveness. Isolated
equine anterior pituitary cells were pre-incubated with media containing 10 nM
CRH or vehicle for 20 hours before being loaded onto columns and perifused with
0.02 nM CRH and 100 nM cortisol. Columns were given a 5-minute pulse of arginine
vasopressin (AVP, 10 nM), perifused for 4 hours with 0 (control) or 1 nM IL
1beta, then given a further 5-minute pulse of AVP (10nM). ACTH was measured in 5
minute fractions. In the setting of CRH pre-incubation, cells perifused with IL
1beta for 4 hours showed increased basal ACTH secretion compared to control (114
+/- 6 pM vs. 86 +/- 4 pM [means +/- S.E.M.], p < 0.001) and a significantly
greater ACTH response to the final AVP pulse (240 +/- 32% vs. 96 +/- 30%, p =
0.009, expressed as % of ACTH response to the initial AVP pulse). The
potentiation of AVP-stimulated ACTH release by IL-1 was not observed in cells pre
incubated with vehicle alone. In conclusion, IL-1 increases ACTH release in
equine corticotroph cells pre-incubated with CRH and potentiates responsivity to
AVP.
PMID- 11014383
TI - Association between parathyroid hormone (PTH)/PTH-related peptide receptor gene
polymorphism and the extent of bone mass reduction in primary
hyperparathyroidism.
AB - Genetic contributions to bone mineral density (BMD) and bone turnover are well
known. In the present study, we analyzed the relationship between polymorphism of
parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene existing in
exon M7 and the clinical characteristics of primary hyperparathyroidism (pHPT).
PTH/PTHrP receptor genotypes were analyzed in 92 pHPT patients by direct sequence
to determine whether nucleotide 1417 of the cDNA was C or T. BMD levels at the
lumbar spine and at the radius before and one year after parathyroidectomy, as
well as serum levels of calcium, phosphorus, alkaline phosphatase (ALP) and
intact PTH were measured. Although there were no significant differences in serum
levels of calcium, phosphorus and intact PTH, ALP was significantly lower in the
CT genotype compared with the TT genotype. BMD level at the radius was
significantly higher in the CT genotype than in the CC genotype. Moreover, an
increase in radial BMD one year after parathyroidectomy was significantly less in
CT genotype than two other genotypes (CC, TT). The present study is the first to
indicate that the polymorphism of PTH/PTHrP receptor gene is closely related to
the extent of bone mass reduction in pHPT and that this polymorphism would be one
of the genetic factors responsible for the severity of the pathological state of
pHPT.
PMID- 11014384
TI - Effect of subclinical hypothyroidism on body fluid compartments.
AB - OBJECTIVE: The present study was aimed to assess the effects of subclinical
hypothyroidism on body composition (BC). SUBJECTS: Thirty-one women (age: 37 +/-
9.9 years) with a wide range of body mass index (BMI) were studied. Subclinical
hypothyroidism was defined by a basal TSH > or = 4 mU/L and/or TRH stimulated
peak > or = 30 mU/L. MEASUREMENTS: For each subject, weight, height, BMI,
multifrequency bioelectrical impedance spectroscopy (BIS) and D2O and NaBr
dilution tests were performed to assessed total body water (TBW) and
extracellular water (ECW). Thyroid function (basal and TRH stimulated TSH, free
T3, and free T4) were determined from fasting blood samples for all subjects.
Total body dual energy X-ray absorptiometry (DXA) were used to measure fat mass
(FM) and lean mass (Lean). RESULTS: The results of BIS were compared with the TBW
and ECW estimated by the dilution techniques on the same individuals. The
correlation was R2 = 0.65 for impedance at 5 kHz and ECW by NaBr and R2 = 0.72
for impedance at 100 kHz and TBW by D2O. Intracellular water (ICW) was calculated
as differences between TBW and ECW measured by dilution methods. Percent of ECW
and ICW were related to BMI (ANOVA, p < 0.001). No difference in TBW, body water
distribution and body composition related to thyroid function was demonstrated.
CONCLUSIONS: In our patients affected with subclinical hypothyroidism, with or
without obesity, only obesity appeared related to TBW, ECW and ICW; the
subclinical hypothyroidism, on the contrary, had no effect on compartments of
body fluids. Bioimpedance is a valid tool to assess body fluid distribution in
subclinical hypothyroidism.
PMID- 11014385
TI - Myxedema coma of both primary and secondary origin, with non-classic presentation
and extremely elevated creatine kinase.
AB - Myxedema coma is a rare, often fatal endocrine emergency that concerns elderly
patients with long-standing primary hypothyroidism; myxedema coma of central
origin is exceedingly rare. Here, we report a 37-year-old woman in whom classical
symptoms of hypothyroidism had been absent. Six years earlier, she had severe
obstetric hemorrhage and, shortly after, two subsequent episodes of pericardial
effusion. On the day of admission, pericardiocentesis was performed for the third
episode of pericardial effusion. Because of the subsequent grave arrhythmias and
unconsciousness, she was transferred to our ICU. Prior to the endocrine
consultation, a silent myocardial infarction had been suspected, based on the
extremely high serum levels of creatine kinase (CK) and isoenzyme CK-MB. However,
based on thyroid sonography, pituitary computed tomography, elevated titers of
antithyroid antibodies and pituitary stimulation tests, the final diagnosis was
myxedema coma of dual origin: an atrophic variant of Hashimoto's thyroiditis and
post-necrotic pituitary atrophy (Sheehan syndrome). Substitutive therapy caused a
prompt clinical amelioration and normalization of CK levels. Our patient is the
first case of myxedema coma of double etiology, and illustrates how its
presentation deviates markedly from the one endocrinologists and physicians at
ICU are prepared to encounter. In addition, cardiac problems as those of our
patient should not discourage from substitutive treatment (using L-thyroxine and
the gastrointestinal route of absorption), if the age is relatively low.
PMID- 11014386
TI - HIV-1 protease inhibitors induce an increase of triglyceride level in HIV
infected men without modification of insulin sensitivity: a longitudinal study.
AB - We investigated longitudinally the effect of protease inhibitors (PI) on insulin
sensitivity, glycemia, and serum lipids in HIV-infected patients. Ninety-one
consecutive patients treated with PI for at least 12 months were included in this
study. Fasting glycemia, lipid profile, insulinemia, CD4 T lymphocytes, and
plasma HIV-1 RNA were performed at baseline and on PI therapy. Insulin
sensitivity and insulin secretion were measured by the homeostasis model
assessment (HOMA MODEL) using the fasting glucose and insulin concentrations.
Triglycerides (+ 0.34 mmol/l, SD = 1.07, p = 0.001) and cholesterol (+ 1.07
mmol/l, SD = 1.21, p= 0.001) significantly increased on PI therapy. Fasting
glycemia, insulin sensitivity, and insulin secretion were not modified after PI
therapy. PI therapy significantly increased body mass index (0.35 kg/m2, p <
0.05). Serum lipid changes correlated with changes in the CD4+ cell count.
Lipodystrophy was observed in 40.6% of patients treated with PI. Our longitudinal
study found that PI therapy had no major impact on fasting glycemia, insulin
sensitivity, and insulin secretion. These findings are not consistent with
previous cross-sectional studies, which did not include baseline measurements
before PI initiation. However, we observed a similar profile of lipid changes
induced by PI therapy. These results suggest that PI could be responsible for the
development of hypertriglyceridemia by a mechanism independent of insulin
resistance which remains to be elucidated.
PMID- 11014387
TI - A novel dominant-negative mutation of the hepatocyte nuclear factor-1alpha gene
in Japanese early-onset type 2 diabetes.
AB - We investigated the presence and the function of hepatocyte nuclear factor-1alpha
(HNF-1alpha) mutations in 26 Japanese subjects with type 2 diabetes. The subjects
were between 20 and 39 years of age on diagnosis and had diabetic first-degree
relatives. Two different frameshift mutations were found in 2 subjects (8 %). One
novel mutation, T539fsdelC (deletion of C in codon 539 for Thr), is predicted to
generate a protein of normal 539 residues at the N-terminus followed by an
abnormal 119 amino acid protein. The mutation, P291fsinsC (insertion of C in
codon 291 for Pro) should lead to production of a truncated protein of 315 amino
acids. Transfection reporter assay using MIN6 and HepG2 cells revealed both
mutations to have null function in the transactivation of reporter gene
expression. When transfected with wild-type gene, these mutations behaved as
dominant-negative regulators in both cells. An equimolar amount of T539fsdelC
reduced wild-type activity by approximately 80% in MIN6 cells, while the same
concentration of P291fsinsc reduced it by 30%. The sequences responsible for the
transactivation activity of HNF-1alpha are confined largely to amino acids 547
628, so that the T539fsdelC mutation, which affects this entire region, replacing
amino acids 540-631 with an abnormal 119 amino acid protein, may acquire a potent
dominant-negative function.
PMID- 11014388
TI - Use of an intact mouse skeletal muscle preparation for endocrine vascular
studies: evaluation of the model.
PMID- 11014389
TI - "Statistical significance and clinical significance are not synonyms!".
PMID- 11014390
TI - Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia.
AB - BACKGROUND: Postherpetic neuralgia (PHN) is a vexing problem occurring in 10 to
20 percent of people with from herpes zoster (shingles). Anecdotal reports show
that fluphenazine enhances the effects of amitriptyline for the treatment of PHN.
The aim of this study was to determine, in a controlled manner, whether this was
the case. METHODS: In a double-blind placebo-controlled study, 49 patients with
PHN were randomly assigned to four treatment groups: Group 1, amitriptyline;
Group 2, amitriptyline and fluphenazine; Group 3, fluphenazine; Group 4, a
placebo. An active placebo was used to mimic the anticholinergic side effects of
dry mouth. The study lasted 8 weeks, with weekly progress evaluations with use of
visual analog scales (VAS), the McGill Pain Questionnaire (MPQ), and a side
effects scale. RESULTS: A statistically significant decrease was seen in pain in
Groups 1 and 2, and no significant changes were seen in Groups 3 and 4. There was
no significant difference when fluphenazine was added to amitriptyline.
CONCLUSION: These data support the effectiveness of amitriptyline in treatment of
PHN, but do not support the addition of fluphenazine.
PMID- 11014391
TI - Flumazenil potentiation of postoperative morphine analgesia.
AB - OBJECTIVE: The goal of this study was to test the effect of concomitant
administration of flumazenil (FL) and morphine (MO) on immediate postoperative
analgesia and the MO requirement to control pain in human beings. DESIGN AND
INTERVENTIONS: Thirty-six patients undergoing inguinal hernioplasty under
lidocaine epidural anesthesia were enrolled in this double-blind, randomized,
controlled study. On the first complaint of pain, either MO (2 mg) only or MO (2
mg) plus FL (0.2 mg) was administered. Additional doses of the same medications
administered via a patient-controlled analgesia device with a 10-minute lockout
period were available thereafter. The study continued for 2 hours after the
loading doses of the medications were administered, with an additional 2-hour
period of observation. RESULTS: Thirty-two patients completed the study. Both
groups reached a similar satisfactory equianalgesic state (2 in a 0-10 visual
analogue scale). The MO plus FL group consumed 9.5 +/- 1.1 mg of MO versus 14.1
+/- 1.1 mg of MO (p < 0.001) in the MO only group. The MO plus FL patients were
subjectively (visual analogue scale) more comfortable and less sedated than the
MO patients. "Fine" coordination (using an electronic maze) and "coarse"
coordination (measured by transferring a pen from one hand to another as rapidly
as possible with both arms placed inside an 80-cm metal frame) in the MO group
were worse than in the MO plus FL group. End-tidal CO2 increased and blood
pressure decreased in the MO group. There were few and insignificant side effects
in the MO group. None of these patients required an MO antagonist, and recovery
was prolonged in none. CONCLUSIONS: Flumazenil afforded lower MO consumption
during the immediate postoperative period. Cognitive, hemodynamic, and
respiratory functions were better after MO plus FL than after MO alone.
PMID- 11014392
TI - Evaluating skin anesthesia after administration of a local anesthetic system
consisting of an S-Caine patch and a controlled heat-aided drug delivery (CHADD)
patch in volunteers.
AB - OBJECTIVE: The objective of this study was to evaluate the depth and duration of
skin anesthesia after the administration of a local anesthetic system consisting
of an S-Caine (Zars, Salt Lake City, UT) patch coupled with a controlled heat
aided drug delivery (CHADD; Zars) patch. DESIGN: The study design was a
randomized, double-blind, placebo-controlled, two-period crossover trial.
PATIENTS: Twelve healthy adult volunteers between the ages of 18 and 50 years
were enrolled. INTERVENTIONS AND OUTCOME MEASURES: After administration of the
study drug or placebo, vital signs (blood pressure, pulse, respiratory rate) were
monitored and recorded, and depth and duration of anesthesia were determined and
recorded at defined intervals for 10 to 120 minutes after treatment. Depth of
anesthesia was measured with a 21-gauge short-bevel needle attached to a depth
gauge, and duration was measured using a 0 to 2 (0 = no sensation, 1 = dull
sensation, 2 = sharp scratching sensation) verbal report scale. RESULTS:
Statistically significant differences were noted in both depth and duration of
anesthesia between the active and placebo groups. The posttreatment mean for
anesthetic depth in the active group was 6.8 mm compared with 4.7 mm for control
group (p = 0.050). The median anesthetic duration was greater than 120 minutes
for the active group compared with less than 10 minutes for the placebo group (p
= 0.001). CONCLUSIONS: The local anesthetic system consisting of a combination of
S-Caine and CHADD patches provided a statistically significant dermal anesthesia
effect compared with placebo in this volunteer study. If confirmed in other
studies, this system has promise as a noninvasive method of producing dermal
anesthesia for minor surgical procedures or intravenous insertion.
PMID- 11014393
TI - Topical lidocaine patch relieves a variety of neuropathic pain conditions: an
open-label study.
AB - OBJECTIVE: Our goal was to perform a pilot study to assess the effectiveness and
tolerability of a topical lidocaine patch (Lidoderm) for the treatment of
peripheral neuropathic pain conditions other than postherpetic neuralgia. DESIGN:
This was an open-label prospective study. PATIENTS: Sixteen patients with
refractory peripheral neuropathic pain conditions who had reported intolerable
side effects or inadequate pain relief with antidepressant, anticonvulsant,
antiarrhythmic, and opioid medications participated in this study. Diagnoses
included postthoracotomy pain, stump neuroma pain, intercostal neuralgia,
diabetic polyneuropathy, meralgia paresthetica, complex regional pain syndrome,
radiculopathy, and postmastectomy pain. OUTCOME MEASURES: A six-item Pain Relief
Scale was used (0 = worse pain, 1 = no change, 2 = slight relief, 3 = moderate
relief, 4 = a lot of relief, 5 = complete relief). RESULTS: Moderate or better
pain relief was reported by 13 of the 16 participants (81%). One patient stopped
treatment after 4 days due to lack of relief. The remaining 15 patients had a
mean duration of patch use of 6.2 weeks with continued relief. Only 1 patient
reported a side effect, a mild skin irritation. CONCLUSIONS: The Lidoderm patch
provided clinically meaningful pain relief in most of these refractory
neuropathic pain patients without side effects. Controlled trials need to be
performed to confirm these preliminary findings.
PMID- 11014394
TI - Fitness and perceived exertion in patients with fibromyalgia syndrome.
AB - OBJECTIVE: The aim of this study was to evaluate the cardiorespiratory fitness
and perceived exertion of female patients with fibromyalgia syndrome (FMS)
compared with that of healthy female subjects. DESIGN AND SUBJECTS: This was
designed as a cross-sectional case-control study, with a consecutive sample of 30
female patients with FMS and an age-matched control group of 67 healthy female
subjects. SETTING: This study was conducted at the multidisciplinary pain center
of a university hospital in a city of more than 1 million inhabitants. OUTCOME
MEASURES: A cardiorespiratory fitness index (PWC65%/kg) and an original perceived
exertion index (B65%) were obtained from the heart rates and perceived exertions
scored on a 10-point Borg scale during a submaximal cycle ergometer test. Average
indexes for the FMS patients and control subjects were compared. RESULTS: The
mean cardiorespiratory fitness index of the FMS patients was not significantly
different from that of the controls. The mean perceived exertion index in the FMS
patients was significantly greater than that of the controls, meaning that the
FMS patients systematically reported higher ratings of perceived exertion during
exercise. CONCLUSIONS: Cardiorespiratory fitness, as expressed by a submaximal
work capacity index, seems normal in female patients with FMS compared with age-
and sex-matched healthy individuals. The fact that FMS patients overscore their
perception of exertion may be due to a greater overlap of peripheral pain and
perceived exertion perceptions during exercise. This observation should be noted
when using perceived exertion scores to prescribe and monitor exercise in FMS
patients.
PMID- 11014395
TI - Biopsychosocial screening questionnaire for patients with low back pain:
preliminary report of utility in physiotherapy practice in Northern Ireland.
AB - OBJECTIVE: The aim of this study was to investigate the potential utility of a
new biopsychosocial screening questionnaire (Acute Low Back Pain Screening
Questionnaire) by exploring the relation between it and several physical risk
factors and posttreatment outcomes so as to establish a cutoff point for the
local population. The relation between the screening questionnaire and valid and
reliable outcome measures of pain and functional disability was also explored.
DESIGN: Cross-sectional and longitudinal studies were conducted on patients
referred for physiotherapy for low back pain to a large Healthcare Trust in
Northern Ireland. Before initial assessment, patients completed the screening
questionnaire and outcome measures, were questioned about known physical risk
factors, and then received physiotherapy. At final discharge, the outcome
variables--the "number of treatments" and patient's current work status ("return
to work [yes/no]")--were recorded, and patients recompleted the outcome measures.
PATIENTS: One hundred eighteen patients gave written informed consent to
participate in this study. RESULTS: Significant associations were detected
between questionnaire scores and pretreatment "leisure time exercise," "analgesic
medication use," and "subjective anesthesia"; posttreatment "return to work"; and
"number of physiotherapy treatments" as well as pain and functional disability
measures. A cutoff "at-risk" score of 112 was calculated, which correctly
classified 74% of patients who received more than six treatments and 80% of
patients who failed to return to work at the end of treatment. CONCLUSIONS: The
findings of this study provide preliminary evidence of the utility of this
biopsychosocial screening questionnaire for future use in clinical intervention
studies in the Northern Ireland National Health Service. Further comparative
investigations in other health care settings are warranted.
PMID- 11014396
TI - Chronic pain among children and adolescents: physician consultation and
medication use.
AB - OBJECTIVE: The goal of this study was to assess physician consultation and use of
medication in Dutch children and adolescents (0-18 years old) having chronic pain
in relation to sociodemographic factors and pain characteristics. DESIGN: This
was a population-based cross-sectional survey. A questionnaire was either mailed
to the participants' parents or distributed at school, and it was filled out by
the parents (for children aged 0-7 years) or by the participant (for children and
adolescents aged 8-18 years). SETTING: The study was conducted in the Rotterdam
area. PATIENTS: Participants included a random sample of 1,300 children aged 0 to
3 years taken from the register of population. In addition, 41 schools were
selected to obtain a representative sample of 5,336 children and adolescents aged
4 to 18 years. OUTCOME MEASURES: Reported physician consultation and medication
use were assessed. RESULTS: Of the 6,636 children and adolescents surveyed, 5,424
(82%) responded. A total of 1,358 respondents (25%) reported chronic pain. Of
these, 57% had consulted a physician and 39% had used medication for the pain.
Respondents with earache, more intense pain, and more frequent pain and those
attending lower vocational training programs were more likely to consult a
physician for the pain than the average respondent. Respondents with earache,
sore throat, headache, more intense pain, and multiple pain; children aged 0 to 3
years; and girls were more likely to use medication for the pain. Logistic
regression analyses showed that for physician consultation, the most significant
predictive factors were the intensity of pain, age, and earache as well as the
level of education for respondents aged 12 to 16 years. The use of medication was
predicted by earache, headache, limb pain, intensity of pain, and age.
CONCLUSIONS: Chronic pain is a common complaint in children and adolescents,
frequently resulting in consultation of a physician and medication use. Regarding
physician consultation, children and adolescents with a lower educational level
seem to be a group at risk.
PMID- 11014397
TI - Predictors of participation in primary care group-format back pain self-care
interventions.
AB - OBJECTIVE: The goal of this study was to explain how primary care back pain
patients who volunteer for a group-format self-care intervention differ from
nonvolunteers. This is relevant to the generalizability of studies that rely on
volunteers as well as the characteristics of patients who do not seek out self
care interventions. SETTING: This study was conducted at a large health
maintenance organization in western Washington state. PATIENTS: "Volunteers" (n =
481) were primary care back pain patients participating in randomized trials of a
self-management intervention who were recruited through passive nonintensive
means (a mailed invitation). "Nonvolunteers" (n = 967) consisted of a
representative sample of consecutive back pain patients. We compared the baseline
characteristics of these two groups. RESULTS: The relatively small percentage
(8%) of primary care back pain patients who volunteered for, and ultimately
participated in, group self-management classes tended to be white, older, better
educated, and more likely to be retired than nonvolunteers. The two groups did
not differ significantly on most clinical measures, including pain intensity and
persistence. Patients experiencing the highest (and lowest) levels of pain
related activity interference were less likely to volunteer than those with
moderate activity limitations, however. CONCLUSIONS: Those individuals
volunteering to participate in a group-format self-care intervention in a primary
care setting differed from nonvolunteers primarily on demographic measures as
opposed to clinical measures. Back pain patients experiencing the highest levels
of activity limitations were somewhat less likely to participate than those with
moderate activity limitations. Recruitment for effective self-care interventions
is an important issue in determining their impact on a population basis.
PMID- 11014398
TI - Use of virtual reality for adjunctive treatment of adult burn pain during
physical therapy: a controlled study.
AB - OBJECTIVE: The pain experienced by burn patients during physical therapy range of
motion exercises can be extreme and can discourage patients from complying with
their physical therapy. We explored the novel use of immersive virtual reality
(VR) to distract patients from pain during physical therapy. SETTING: This study
was conducted at the burn care unit of a regional trauma center. PATIENTS: Twelve
patients aged 19 to 47 years (average of 21% total body surface area burned)
performed range of motion exercises of their injured extremity under an
occupational therapist's direction. INTERVENTION: Each patient spent 3 minutes of
physical therapy with no distraction and 3 minutes of physical therapy in VR
(condition order randomized and counter-balanced). OUTCOME MEASURES: Five visual
analogue scale pain scores for each treatment condition served as the dependent
variables. RESULTS: All patients reported less pain when distracted with VR, and
the magnitude of pain reduction by VR was statistically significant (e.g., time
spent thinking about pain during physical therapy dropped from 60 to 14 mm on a
100-mm scale). The results of this study may be examined in more detail at
www.hitL.washington.edu/projects/burn/. CONCLUSIONS: Results provided preliminary
evidence that VR can function as a strong nonpharmacologic pain reduction
technique for adult burn patients during physical therapy and potentially for
other painful procedures or pain populations.
PMID- 11014399
TI - Hypogonadism in patients treated with intrathecal morphine.
AB - OBJECTIVE: The objective of this study was to investigate the hypothalamic
pituitary-gonadal response to intrathecal opioids. PATIENTS: Thirty patients
receiving intrathecal morphine for chronic nonmalignant pain were studied for
clinical and biochemical evidence of hypogonadism. Ten men and 10 postmenopausal
women with chronic pain of similar duration but who were not receiving any form
of opioid therapy acted as control subjects. RESULTS: Men and both premenopausal
and postmenopausal women had evidence of hypogonadism with low levels of serum
testosterone or estrogen coupled with low levels of pituitary gonadotrophins.
Control subjects had hormone levels in the expected range for their sex and age.
Two men demonstrated recovery after ceasing intrathecal opioid therapy.
CONCLUSIONS: Hypogonadotrophic hypogonadism is a common complication of
intrathecal opioid therapy in both men and women.
PMID- 11014400
TI - Effect of acupuncture upon experimentally induced ischemic pain: a sham
controlled single-blind study.
AB - OBJECTIVE: To investigate the hypoalgesic effect of true and sham acupuncture
upon experimentally induced ischemic pain. DESIGN: Human volunteers (n = 60) were
required to attend two sessions for pain induction using a submaximal effort
tourniquet technique; on the first occasion, baseline pain scores were recorded
and on the second, 48 hours later, subjects were randomly allocated to one of
five groups: Control, Treatment Groups 1 or 2, or Placebo Groups 1 or 2.
SUBJECTS: Healthy human volunteers. INTERVENTION: In all the Treatment and
Placebo Groups, subjects received some form of needle acupuncture 15 minutes
before, and 5 minutes during, the pain induction procedure on the second day.
Treatment Group 1 received acupuncture on acupuncture points situated distal to
the tourniquet, whereas Treatment Group 2 received acupuncture on acupuncture
points situated proximal to the tourniquet. In Placebo Groups 1 and 2, subjects
received 'sham' acupuncture either on nonacupuncture points (Placebo Group 1) or
on acupuncture points (Placebo Group 2) using (standardized) minimal levels of
stimulation. A licensed acupuncturist who was not involved in data collection and
analyses carried out all treatments. OUTCOME MEASURES: Pain was assessed using a
computerized visual analog scale (VAS) and a McGill Pain Questionnaire (MPQ).
RESULTS: Analysis of VAS scores using ANOVA revealed no significant differences
between groups (e.g., VAS sum of differences data (mean +/- SEM): Treatment Group
1: 90+/-47, Treatment Group 2: 187+/-56, Placebo Group 1: 152+/-40, Placebo Group
2: 121+/-42, CONTROLS: 46+/-24, p>0.05). Analysis of MPQ percentage difference
scores using one-way ANOVA revealed some isolated effects in the subjective
descriptors and the Pain Rating Index, both for Treatment Group 2 and Placebo
Group 2, proving them superior to any of the other groups. CONCLUSION: The
results of the study provide no convincing evidence for a superior hypoalgesic
effect of acupuncture compared with "sham" procedures on this model of
experimental pain.
PMID- 11014401
TI - Severe lightning pain after subarachnoid block in a patient with neuropathic pain
of central origin: which drug is best to treat the pain?
AB - OBJECTIVE: There have been many reports that spinal anesthesia induces severe
lightning pain in the lower limbs of patients with phantom limb pain, tabes
dorsalis, or causalgia. We report on a patient with neuropathic pain of central
origin who showed newly developed severe lightning pain after therapeutic
subarachnoid block (SAB). We performed SAB 16 times in this patient, and he
complained of severe pain each time. We investigated which drug was best for
treating such induced pain by administering various drugs to the patient.
SETTING: The patient was hospitalized for treatment and observation. PATIENT: The
patient was a 48-year-old man with neuropathic pain secondary to an incomplete
spinal cord injury at the cervical segment. INTERVENTIONS: Various drugs were
administered for relieving the newly developed severe pain, and the effectiveness
of these agents was compared. RESULTS AND CONCLUSIONS: Intravenous thiopental,
fentanyl, butorphanol, ketamine, midazolam, droperidol, and sevoflurane-oxygen
anesthesia were quite effective. Intramuscular butorphanol was not effective.
Intravenous physiologic saline and atropine sulfate as a placebo, intrathecal
morphine hydrochloride, intravenous mexiletine, and lidocaine were ineffective.
Intravenous thiopental (approximately 1 mg/kg) was thought to obtain the best
pain relief because it stopped the pain quickly, the dose needed was
subanesthetic, and there was no adverse effect.
PMID- 11014402
TI - Sex-specific and general roles of pain-related anxiety in adjustment to chronic
pain: a reply to Edwards et al.
PMID- 11014403
TI - Phage therapy: the peculiar kinetics of self-replicating pharmaceuticals.
AB - The specter of antibiotic-resistant bacteria has provoked renewed interest in the
possible use of bacteriophages to control bacterial infections. We argue that
clinical application of phage therapy has been held back by a failure to
appreciate the extent to which the pharmacokinetics of self-replicating agents
differ from those of normal drugs. For self-replicating pharmaceutical agents,
treatment outcome depends critically on various density-dependent thresholds,
often with apparently paradoxical consequences. An ability to predict these
thresholds and associated critical time points is a necessity if phage therapy is
to become clinically practicable.
PMID- 11014404
TI - Increased drug delivery to the brain by P-glycoprotein inhibition.
AB - BACKGROUND: Although the antidiarrheal loperamide is a potent opiate, it does not
produce opioid central nervous system effects at usual doses in patients. On the
basis of in vitro studies demonstrating that loperamide is a substrate for the
adenosine triphosphate-dependent efflux membrane transporter P-glycoprotein, we
postulated that inhibition of P-glycoprotein with quinidine would increase entry
of loperamide into the central nervous system with resultant respiratory
depression. METHODS: To test this hypothesis, a 16-mg dose of loperamide was
administered to eight healthy male volunteers in the presence of either 600 mg
quinidine, a known inhibitor of P-glycoprotein, or placebo. Central nervous
system effects were measured by evaluation of the respiratory response to carbon
dioxide rebreathing as a measure of opiate-induced respiratory depression.
RESULTS: Loperamide produced no respiratory depression when administered alone,
but respiratory depression occurred when loperamide (16 mg) was given with
quinidine at a dose of 600 mg (P < .001). These changes were not explained by
increased plasma loperamide concentrations. CONCLUSION: This study therefore
demonstrates first the potential for important drug interactions to occur by a
new mechanism, namely, inhibition of P-glycoprotein, and second that the lack of
respiratory depression produced by loperamide, which allows it to be safely used
therapeutically, can be reversed by a drug causing P-glycoprotein inhibition,
resulting in serious toxic and abuse potential.
PMID- 11014405
TI - Pharmacokinetics of L-carnitine in patients with end-stage renal disease
undergoing long-term hemodialysis.
AB - OBJECTIVE: L-Carnitine is an endogenous molecule involved in fatty acid
metabolism. Secondary carnitine deficiency may develop in patients with end-stage
renal disease undergoing long-term hemodialysis because of dialytic loss. In
these patients L-carnitine can be administered to restore plasma and tissue
levels. The objective of this study was to evaluate the pharmacokinetics of
intravenous L-carnitine in patients undergoing long-term hemodialysis. METHODS:
Twelve patients undergoing three dialysis sessions/week received L-carnitine
intravenously (20 mg x kg(-1)) at the end of each dialysis session for 9 weeks.
Plasma samples were analyzed for L-carnitine, acetyl-L-carnitine, and total
carnitine by HPLC. RESULTS: Under baseline conditions, the mean +/- SD
predialysis plasma concentration of L-carnitine was 19.5 +/- 5.6 micromol/L,
decreasing to 5.6 +/- 1.9 micromol/L at the end of the dialysis session. These
concentrations were substantially lower than endogenous levels in healthy human
beings. Under baseline conditions the extraction ratios of L-carnitine and acetyl
L-carnitine by the dialyser were 0.74 +/- 0.07 and 0.71 +/- 0.11, respectively.
During repeated dosing, there was accumulation of L-carnitine in plasma, and
after 9 weeks of dosing, the predialysis and postdialysis plasma levels were 191
+/- 54.1 and 41.8 +/- 13.0 micromol/L, respectively. The predialysis and
postdialysis plasma levels of L-carnitine decreased once dosing was ceased but
had not returned to pretreatment levels after 6 weeks. CONCLUSION: The study
demonstrated that removal of L-carnitine by hemodialysis is extremely efficient
and that patients undergoing hemodialysis had plasma concentrations that were
substantially lower than normal, particularly during dialysis. During repeated
administration of L-carnitine, the predialysis and postdialysis concentrations of
the compound increased steadily, reaching an apparent steady state after about 8
weeks. It is proposed that this accumulation arose from the distribution of L
carnitine into a deep tissue pool that includes skeletal muscle.
PMID- 11014406
TI - Pharmacokinetics of nicotine in kidney failure.
AB - BACKGROUND: Smoking is an important risk factor for cardiovascular and
cerebrovascular complications in patients with chronic kidney failure. Very high
plasma nicotine concentrations have been reported in patients with severe kidney
failure, indicating that the disposition of nicotine in these patients may be
different. The purpose of this study was to assess the pharmacokinetics of
intravenously administered nicotine in healthy subjects and in patients with
kidney failure. METHODS: Nine healthy subjects (glomerular filtration rate [GFR],
84 to 143 mL/min/1.73 m2), four patients with mild kidney failure (GFR, 63 to 73
mL/min/1.73 m2), five patients with moderate kidney failure (GFR, 18 to 36
mL/min/1.73 m2), and six patients with severe kidney failure (GFR, 1 to 10
mL/min/1.73 m2) were recruited. Three patients were treated with continuous
ambulatory peritoneal dialysis. An intravenous infusion of nicotine (0.028 mg/kg)
was given for 10 minutes. Nicotine and cotinine concentrations were measured in
plasma, urine, and peritoneal dialysate from 0 to 24 hours after start of
infusion RESULTS: There were significant correlations between GFR and total
clearance, nonrenal and renal clearance of nicotine, area under the plasma
concentration-time curve extrapolated to infinity, terminal elimination half
life, and mean residence time. Nonrenal clearance was 1303 mL/min and 661 mL/min
in healthy subjects and patients with severe kidney failure, respectively. Only
1% to 2% of the nicotine dose was excreted unchanged in a 24-hour collection of
peritoneal dialysate. The elimination of cotinine was also decreased in patients
with kidney failure. CONCLUSION: Progressive kidney failure is associated with a
gradual decrease of renal and nonrenal elimination of nicotine.
PMID- 11014407
TI - Disposition and safety of omapatrilat in subjects with renal impairment.
AB - BACKGROUND: Omapatrilat, a vasopeptidase inhibitor, preserves natriuretic
peptides and inhibits the renin angiotensin aldosterone system by simultaneously
inhibiting neutral endopeptidase and angiotensin-converting enzyme. METHODS: Oral
omapatrilat, 10 mg/d, was administered for 8 to 9 days to three groups of eight
subjects with varying degrees of renal function (CLCR values, normal > or = 80;
mild to moderate impairment < 80 to > or = 30; severe impairment < 30 mL/min/1.73
mL2) and to six subjects undergoing maintenance hemodialysis. Omapatrilat and its
metabolites (phenylmercaptopropionic acid, S-methylomapatrilat, S
methylphenylmercaptopropionic acid, and cyclic S-oxide-omapatrilat) were
quantified in plasma by a validated liquid chromatography/mass spectrometry
method. The model, Cmax or AUC(0-T) = intercept + slope x CLCR, was tested for a
possible linear correlation between Cmax (peak plasma concentrations) or AUC(0-T)
(area under plasma concentration versus time curve) and CLCR. RESULTS: For
omapatrilat and its inactive metabolites, phenylmercaptopropionic acid, S
methylomapatrilat, and S-methylphenylmercaptopropionic acid, the median times to
peak plasma concentrations (tmax) were 1.5 to 2, 2 to 3, 2.5 to 3.5, and 7 to 10
hours, respectively, and were independent of renal function. After Cmax
attainment, plasma concentrations declined rapidly to about 10% of Cmax values.
Cyclic S-oxide-omapatrilat, a potentially active metabolite, was undetectable at
all sampling time points. Hemodialysis did not decrease circulating levels of
omapatrilat. There was minimal accumulation of omapatrilat and
phenylmercaptopropionic acid and moderate accumulation of the S-methylated
metabolites. For omapatrilat and S-methylphenylmercaptopropionic acid, neither
Cmax nor AUC(0-T) was CLCR dependent. However, AUC(0-T) for
phenylmercaptopropionic acid and both the Cmax and AUC(0-T) for S
methylomapatrilat were CLCR dependent. CONCLUSIONS: The pharmacokinetics of
omapatrilat, the only clinically relevant active compound studied, was
independent of CLCR. For patients with reduced renal function, adjusting initial
omapatrilat dose is not suggested. Hemodialysis did not significantly contribute
to the clearance of omapatrilat. The long-term pharmacodynamic response to
omapatrilat will dictate dose-adjustment needs.
PMID- 11014408
TI - Dose and time dependencies of 5-fluorouracil pharmacokinetics.
AB - OBJECTIVES: The purpose of this study was to examine the interpatient and
intrapatient variability of the Michaelis-Menten plasma parameters of 5
fluorouracil administered according to a schedule combining a bolus of 400 mg/m2
followed by 22-hour infusion of 600 mg/m2 for 2 consecutive days. PATIENTS: A
pharmacokinetic population approach was used to analyze the data from 21 patients
with colorectal cancer. RESULTS: The 5-fluorouracil plasma concentrations versus
time were best described by a two-compartment model with nonlinear elimination
from the central compartment. The relationships between the pharmacokinetic
parameters and patient characteristics were tested. On day 1 the mean values
(with interindividual variability as expressed by the coefficient of variation)
were 1390 mg x h(-1) (20%), and 5.57 mg x L(-1) (22%) for the maximum rate of
elimination, and the half-saturating plasma concentration. The maximum rate of
elimination was positively correlated to the body surface area and the percentage
of liver involvement by metastatic disease determined by tomodensitometric
examination. The model was successfully tested with independent data sets
corresponding to other schedules. The analysis of this intrapatient variability
showed that the half-saturating plasma concentration increased from day 1 to day
2, especially in the patients with low lymphocyte cell dihydropyrimidine
dehydrogenase activity. CONCLUSION: The pharmacokinetic parameters obtained in
this study would be useful to predict the 5-fluorouracil plasma concentrations
following other schedules of administration of 5-fluorouracil and to study the
possible pharmacokinetic interactions between 5-fluorouracil and other drugs.
PMID- 11014409
TI - In vivo drug-drug interaction studies--a survey of all new molecular entities
approved from 1987 to 1997.
AB - Ninety-eight new molecular entities applications approved between 1987 to 1991
(period I) and 193 applications for new molecular entities between 1992 to 1997
(period II) were surveyed for drug-drug interaction studies. In period I (used as
a comparator), 32 applications contained drug-drug interaction studies for a
total of 117 studies. In period II, 106 applications reported drug-drug
interaction studies, and the number of studies per new molecular entity ranged
from 0 to 15. Most studies (77%) were performed in healthy subjects, with 44%
using crossover designs, 7% using parallel designs, and the remaining using fixed
sequence designs. The most common dosing scheme for new molecular
entities/interacting drug was multiple dose (47%), whereas single dose/multiple
dose was used in 31% of studies, and single dose/single dose was used in 18% of
studies. Of the 540 drug-drug interaction studies submitted in period II, 80
(15%) resulted in clinically significant labeling statements. Submissions for new
molecular entities to the Center for Drug Evaluation and Research divisions most
likely to include drug-drug interaction studies were neuropharmacology,
cardiorenal, antiviral, and antiinfective drugs. Some drug classes such as
oncology drug products and radioimaging products were least likely to include
drug-drug interaction studies in their submissions. We conclude that the use of
drug-drug interaction studies in the drug development process has increased
between the two periods.
PMID- 11014411
TI - Effect of hydrocortisone on phenylephrine--mean arterial pressure dose-response
relationship in septic shock.
AB - BACKGROUND: Septic shock is characterized by decreased responsiveness to
catecholamines. Because endogenous steroids are known to play a role in the
modulation of vasomotor tone, the purpose of our study was to investigate the
phenylephrine-mean arterial pressure dose-response relationship in patients with
septic shock and the effect of a physiological dose of hydrocortisone on it.
METHODS: Twelve patients meeting usual criteria for septic shock and 12 age
matched control subjects were investigated before and 1 hour after receiving 50
mg intravenous hydrocortisone. Sixteen incremental doses of phenylephrine
(microg/kg/min) were infused, and the effects on mean arterial pressure (mm Hg)
were recorded. A sigmoid model, E = E0 + [Emax x Dgamma/(ED50gamma + Dgamma)],
was fitted to individual data. In this model, E is the predicted effect and D is
the dose of phenylephrine infused. E0 represents the basal value of effect (ie,
the value of mean arterial pressure without drug), Emax is the maximum
theoretical effect, ED50 is the dose of phenylephrine for which an effect of 50%
of Emax is observed, and gamma is the Hill coefficient which accounts for the
sigmoidicity of the curve. RESULTS: As compared with in control subjects, in
patients, E0 was decreased before (58 +/- 8 versus 73 +/- 7 mm Hg) and after (64
+/- 12 versus 82 +/- 10 mm Hg) administration of hydrocortisone (P = .0001 for
group), Emax was reduced before (39 +/- 17 versus 84 +/- 18 mm Hg) and after (77
+/- 26 versus 106 +/- 21 mm Hg) administration of hydrocortisone (P = .0001 for
group), ED50 was not modified, and gamma was increased before (3.5 +/- 1.8 versus
1.3 +/- 0.3) and after (1.9 +/- 1.1 versus 1.3 +/- 0.3) administration of
hydrocortisone (P = .0010 for group). Hydrocortisone similarly increased E0 in
both groups (P = .0003 for sequence, P = .2883 for interaction), increased more
Emax in patients than in control subjects (P < .0001 for sequence; P = .0280 for
interaction), did not change ED50, and decreased y in patients but not in control
subjects (P = .0025 for sequence, P = .0025 for interaction). CONCLUSIONS: In
patients with septic shock, the Emax of phenylephrine is decreased, whereas its
ED50 is not modified, both before and after administration of hydrocortisone. A
physiological dose of hydrocortisone tends to normalize the relationship.
PMID- 11014410
TI - Faster clearance of sustained release verapamil in men versus women: continuing
observations on sex-specific differences after oral administration of verapamil.
AB - Pharmacokinetic studies after administration of 120 mg oral sustained- and
regular-release racemic verapamil were performed in 13 healthy subjects (seven
men, age 74 +/- 4 years [mean +/- SD], weight 69.9 +/- 5.4 kg, and body mass
index 24.6 +/- 2.2]; and six women, age 65 +/- 13 years, weight 65 +/- 9.9 kg,
and body mass index 25.3 +/- 3). Verapamil was measured by HPLC, concentration
versus time data analyzed by noncompartmental models, and statistical analyses
performed by ANOVA for repeated measurements. The area under the concentration
versus time curve (AUC) after administration of sustained-release verapamil was
48,951 +/- 18,079 ng/mL x min(-1) in women compared with 25,595 +/- 10,245 in men
and lower than after administration of regular-release verapamil (63,055 +/-
24,411 for women and 34,686 +/- 25,279 in men; P = .05 for sex-related effect and
P < .02 for formulation effect). AUC ratios of norverapamil (N-demethylated
metabolite) to verapamil after administration of sustained-release verapamil were
1.43 +/- 0.26 in women compared with 1.74 +/- 0.41 in men and 1.43 +/- 0.26 in
women compared with 1.78 +/- 0.37 in men after administration of regular-release
verapamil (P = .1 for sex-related effect and P = .9 for formulation effect).
Apparent oral clearance was 43 +/- 15 mL/min/kg in women compared with 75 +/- 29
in men after administration of sustained-release verapamil and 35 +/- 16
mL/min/kg in women compared with 65 +/- 31 in men after administration of regular
release verapamil (P < .05 for sex-related effect and P < .02 for formulation
effect). Apparent oral clearance of both regular- and sustained-release
formulations of verapamil was faster in men compared with women in contrast to
findings after intravenous administration of verapamil, suggesting that
intestinal processes are a factor in sex-specific difference in drug clearance.
Greater verapamil and norverapamil bioavailability after administration of
regular- compared with sustained-release verapamil also suggests saturable
processes at the intestinal level.
PMID- 11014412
TI - A comparative pharmacodynamic study of IY-81149 versus omeprazole in patients
with gastroesophageal reflux disease.
AB - OBJECTIVE: To evaluate and compare the pharmacodynamic effects of IY-81149 and
omeprazole on gastric pH in patients with gastroesophageal reflux disease.
METHODS: Sixty male and female volunteers with gastroesophageal reflux disease
were enrolled in a double-blind, two-way, crossover, dose-ranging study. Subjects
were randomized into three groups, with each group comparing the effect of one of
three doses of IY-81149 (5, 10, or 20 mg) with 20 mg omeprazole. IY-81149 and
omeprazole were administered once daily for 5 days. Continuous 24-hour pH
measurements were performed before the first dose (baseline) and after the fifth
dose in both periods. Gastric acid suppression was evaluated on the basis of the
following parameters: AUC(0-24), median pH in a 24-hour interval (pHmedian), and
the percent time in a 24-hour interval in which the gastric pH was greater than 4
(tpH > 4). The truncated AUC parameters AUC(0-8), AUC(8-16), and AUC(16-24) were
also calculated. The effects of IY-81149 and omeprazole on gastric pH were
compared by use of analyses of covariance. The dose-response relationship for IY
81149 was also evaluated. RESULTS: There were no statistically significant
differences between 5 mg IY-81149 and 20 mg omeprazole in terms of AUC(0-24),
pHmedian, tpH, 4, AUC(0-8), and AUC(8-16). IY-81149, at 10 mg, produced a
significantly greater gastric acid suppression than omeprazole on the basis of
the values of AUC(0-24), pHmedian, tpH > 4, AUC(8-16), and AUC(16-24).
Administration of 20 mg IY-81149 produced a significantly greater gastric acid
suppression on the basis of all parameters. All doses of IY-81149 were more
effective than omeprazole during 16 to 24 hours after the dose was administered.
CONCLUSIONS: Administration of 10 and 20 mg IY-81149 produced a statistically
significantly greater and prolonged suppression of gastric pH than 20 mg
omeprazole.
PMID- 11014413
TI - Ibuprofen plus caffeine in the treatment of tension-type headache.
AB - BACKGROUND: The effectiveness of caffeine as an adjuvant to ibuprofen has been
documented in investigations of acute pain. Our objectives were to assess this
agent in the treatment of tension-type headache and to establish clinical trial
methods capable of assessing this agent in comparison with various tension
headache treatments. Stopwatch technology was used for measurement techniques.
METHODS: A randomized, double-blind, parallel, multicenter, single-dose, placebo-
and active-controlled study included 301 subjects diagnosed with tension-type
headache. Treatment groups included ibuprofen and caffeine, ibuprofen alone,
caffeine alone, or placebo. Subjects measured onset of relief (both time to first
perceptible relief and time to meaningful relief) after taking a single oral dose
of their assigned medication. Pain intensity and pain relief were rated over a 6
hour study period. Overall evaluation was made on completion of all other
ratings. RESULTS: Ibuprofen and caffeine administered together provided
significantly greater analgesic activity than ibuprofen alone, caffeine alone,
and placebo. Ibuprofen and caffeine administered together demonstrated
significantly shorter times to meaningful improvement in headache relief than
ibuprofen or placebo; significantly greater total analgesia than ibuprofen alone,
caffeine alone, or placebo; and significantly greater peak relief than ibuprofen
alone, caffeine alone, or placebo. Significantly more subjects obtained
meaningful headache relief with ibuprofen and caffeine administered together than
with ibuprofen alone or placebo. More patients reported complete headache relief
with ibuprofen and caffeine administered together than with ibuprofen alone,
caffeine alone, or placebo. Ibuprofen and caffeine administered together was
rated significantly better by patients than either ibuprofen alone, caffeine
alone, or placebo. No subjects ended participation in the study early because of
adverse events. CONCLUSIONS: Sensitive methods have been introduced to assess
differences in analgesia among over-the-counter analgesic agents in relieving
tension-type headache pain. A double-blind study with this method suggests that
ibuprofen and caffeine administered together provides greater analgesic
effectiveness than either component alone.
PMID- 11014414
TI - Effects of the 2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid/kainate
antagonist LY293558 on spontaneous and evoked postoperative pain.
AB - BACKGROUND: Previous studies suggest that 2-amino-3-hydroxy-5-methyl-4-isoxazole
proprionic acid (AMPA)/kainate antagonists reduce experimentally induced pain.
There have been no studies of AMPA/kainate antagonists in clinical pain. METHODS:
Analgesic efficacy of intravenous LY293558 (0.4 or 1.2 mg/kg) was compared with
that of intravenous ketorolac tromethamine (INN, ketorolac; 30 mg) and placebo in
a randomized, double-blind, parallel-group study after oral surgery (n = 70).
Study drugs were administered at the onset of moderate pain; pain intensity and
relief were measured for 240 minutes. RESULTS: High-dose LY293558 and ketorolac
tromethamine were superior to placebo (P < .05) for pain evoked by mouth opening
and one of several measures of spontaneous pain: SPID240 +/- SEM for pain evoked
by mouth opening was highest for ketorolac tromethamine (151 +/- 58),
intermediate for high-dose LY293558 (-45 +/- 35), and least for low-dose LY293558
(-151 +/- 39) and placebo (-162 +/- 50). High-dose LY293558 was superior to
placebo at individual time points (45 to 240 minutes) for pain evoked by mouth
opening but not for spontaneous pain. The spontaneous summed pain intensity
difference over 240 minutes (SPID240 +/- SEM) was highest for ketorolac
tromethamine (303 +/- 84), intermediate for high-dose LY293558 (-51 +/- 40) and
low-dose LY293558 (-96 +/- 45), and least for placebo (-180 +/- 24). LY293558 was
well tolerated, with dose-dependent and reversible side effects including hazy
vision in 20% of patients and sedation in 15%. CONCLUSIONS: This is the first
evidence that an AMPA/kainate antagonist reduces clinical pain. Tests of evoked
pain may be more sensitive to certain analgesics than those of spontaneous pain.
The evaluation of evoked pain as an outcome measure in analgesic trials may
identify potentially useful compounds otherwise missed if only spontaneous pain
is evaluated.
PMID- 11014415
TI - CYP2C19 genetic mutations in North Indians.
AB - OBJECTIVES: To identify defective alleles of CYP2C19 (CYP2C19*2 and *3) in North
Indians. METHODS: One hundred extensive metabolizers and 21 poor metabolizers of
omeprazole were genotyped with respect to CYP2C19*2 and *3 alleles with
polymerase chain reaction-based diagnostic tests. RESULTS: Fifty-two extensive
metabolizers and six poor metabolizers were homozygous with the CYP2C19*1/*1
genotype, and 48 extensive metabolizers and six poor metabolizers were
heterozygous with the CYP2C19*1/*2 genotype. Nine poor metabolizers were
homozygous with the CYP2C19*2/*2 genotype. No extensive or poor metabolizers
demonstrated the presence of the CYP2C19*3 allele. CYP2C19*2 could explain 43%
(9/21) of the poor metabolizers and 57% (24/42) of the defective alleles in poor
metabolizers. Allele frequency of CYP2C19*1 and *2 was 0.7 (95% confidence
interval of 0.65 to 0.75) and 0.3 (95% confidence interval of 0.25 to 0.35),
respectively. Homozygous extensive metabolizers excreted 7.85 +/- 7.6 micromol 5
hydroxyomeprazole in 8 hours, which was 28% more as compared with heterozygous
extensive metabolizers who excreted 5.6 +/- 3.6 micromol 5-hydroxyomeprazole in 8
hours (P < .05). CONCLUSIONS: CYP2C19*2 demonstrated allele frequency of 0.3,
whereas CYP2C19*3 was absent in North Indians. Because CYP2C19*2 is not able to
explain 57% of poor metabolizers, other mutations (CYP2C19*4 to *8) might be
present in North Indians. CYP2C19 demonstrated differential evolution in North
Indians because the frequency of CYP2C19*2 was similar to that in Oriental
subjects, but that of CYP2C19*3 was similar to that in white subjects.
PMID- 11014416
TI - Mechanisms of chloroquine-induced pruritus.
PMID- 11014417
TI - Triptans and coronary spasm.
PMID- 11014419
TI - Cognitive functioning and cerebrospinal fluid concentrations of neuropeptides for
patients with good neurological outcomes after aneurysmal subarachnoid
hemorrhage.
AB - OBJECTIVE: Many patients exhibit cognitive disturbances after aneurysmal
subarachnoid hemorrhage (SAH). Structural and functional neuroimaging has failed
to demonstrate any correlation with these complaints. This study was performed to
investigate whether neuropeptide concentrations in cerebrospinal fluid could be
related to cognitive disturbances after SAH. METHODS: Lumbar cerebrospinal fluid
was obtained, 3 to 6 months after surgery, from 17 patients who experienced good
outcomes after aneurysmal SAH. The samples were analyzed for various
neuropeptides using radioimmunoassays, and the peptide concentrations were
evaluated in relation to scores on standardized neuropsychological tests.
RESULTS: The neuropsychological test results were normal for eight individuals,
whereas the remaining nine patients exhibited various degrees of cognitive
impairment. There was no correlation between the concentrations of arginine
vasopressin or neuropeptide Y and test performance. However, significant
correlations between cognitive impairment and elevated levels of beta-endorphins
(P = 0.02), corticotropin-releasing factor (P = 0.004), and delta sleep-inducing
peptide (P = 0.045) were noted. CONCLUSION: Patients with cognitive impairments
after aneurysmal SAH exhibited higher cerebrospinal fluid concentrations of
endorphins, corticotropin-releasing factor, and delta sleep-inducing peptide than
did those with normal capacity. This is probably attributable to diffuse
derangement of transmitter release in the brain, resulting from the insult or
ensuing complications, although a secondary increase in corticotropin-releasing
factor concentrations caused by increased stress during the testing because of
reduced cognitive capacity cannot be excluded.
PMID- 11014418
TI - The insular lobe: physiopathological and surgical considerations.
AB - OBJECTIVE: Surgery of the insula represents a technical challenge, because of the
proximity of the internal capsule to the lenticulostriate arteries and the lack
of certainty concerning its functionality. Using intraoperative direct cerebral
stimulation, combined with neuronavigation, the authors operated on 12 insular
gliomas. On the basis of this experience, the physiopathological and surgical
implications are discussed. METHODS: A low-grade insular glioma, revealed by
seizures, was diagnosed in 12 right-handed patients with a normal neurological
status. Preoperative magnetic resonance imaging showed that, according to
Yasargil's classification system, three patients harbored Type 3 lesions and nine
patients had Type 5 lesions (10 tumors on the right side and 2 on the left
dominant side). All patients underwent surgery using direct cerebral stimulation,
under general anesthesia in nine patients (motor mapping) and under local
anesthesia in three patients (sensorimotor and language mapping). Ultrasonography
and/or neuronavigation was used in all cases. Preoperative angio-computed
tomographic scanning showed the lenticulostriate arteries in two patients.
RESULTS: The internal capsule was systematically detected, and the language areas
were identified within the left insula in the awake patients. The
lenticulostriate arteries were seen in two patients. Seven patients presented an
immediate postoperative deficit; six of them recovered completely within 3
months. Four resections were total, six were subtotal, and two were partial (left
insula). CONCLUSION: The use of intraoperative direct cerebral stimulation and
neuronavigation allows surgery of the insula with minimization of the risk of
sequelae, but its use is still limited with regard to the dominant hemisphere,
owing to the essential role of this structure in language.
PMID- 11014420
TI - Predicting delayed ischemic deficits after aneurysmal subarachnoid hemorrhage
using a transient hyperemic response test of cerebral autoregulation.
AB - OBJECTIVE: To assess whether the development of delayed ischemic deficits (DIDs)
after aneurysmal subarachnoid hemorrhage can be predicted using transcranial
Doppler ultrasonography and the transient hyperemic response test (THRT).
METHODS: An increase in the middle cerebral artery peak flow velocity (FV) of
more than 9% of baseline values after 5 to 9 seconds of carotid artery
compression was defined as a normal THRT result, indicating good autoregulatory
reserve. The transcranial Doppler criteria for vasospasm were a FV of more than
120 cm/s and a Lindegaard ratio of more than 3. Twenty patients with no immediate
postoperative neurological deficits were studied. The FVs at all of the major
cerebral arteries were measured daily after surgery, and the THRT results were
assessed bilaterally. RESULTS: Five of six patients with abnormal THRT results in
the first examination after surgery (primary THRT impairment) developed DIDs;
none of the remaining patients developed DIDs (Fisher exact test, P = 0.0004).
All five patients with DIDs initially exhibited low FVs but all subsequently
developed increases in FVs to values of more than 150 cm/s and four exhibited FVs
of more than 200 cm/s. The time of onset of DIDs corresponded to the time of
onset of moderate vasospasm (FV > 150 cm/s). None of the patients with initially
normal THRT results developed DIDs, although four patients did exhibit late
(secondary) THRT impairment, which was associated with FVs of more than 120 cm/s.
CONCLUSION: When the effects of primarily impaired (after surgery) autoregulation
are magnified by vasospasm, the risk of DIDs seems to be very high. Vasospasm
alone does not seem to cause DIDs. The development of DIDs could therefore be
predicted using the THRT for patients after aneurysm clipping.
PMID- 11014422
TI - Radiosurgery for childhood intracranial arteriovenous malformations.
AB - OBJECTIVE: The optimal management of intracranial arteriovenous malformations
(AVMs) in children remains controversial. Children with intracranial AVMs present
a special challenge in therapeutic decision-making because of the early
recognition of their future life-long risks of hemorrhage if they are treated
conservatively. The goals of radiosurgery are to achieve complete AVM
obliteration and to preserve neurological function. We present long-term outcomes
for a series of children treated using radiosurgery. METHODS: The findings for 53
consecutive children who underwent at least 36 months of imaging follow-up
monitoring after radiosurgery were reviewed. The median age at the time of
treatment was 12 years (range, 2-17 yr). Thirty-one children (58%) presented
after their first intracranial hemorrhaging episodes, two (4%) after their second
hemorrhaging episodes, and one (2%) after five hemorrhaging episodes. Nineteen
children (36%) presented with unruptured AVMs, and a total of 25 children (47%)
exhibited neurological deficits. AVMs were graded as Spetzler-Martin Grade I
(2%), Grade II (23%), Grade III (36%), Grade IV (9%), or Grade VI (30%). The
median AVM volume was 1.7 ml (range, 0.11-10.2 ml). The median marginal dose was
20 Gy (range, 15-25 Gy). RESULTS: Results were stratified according to AVM
volumes (Group 1, < or =3 ml; Group 2, >3 ml to < or =10 ml; Group 3, >10 ml).
Twenty-eight patients (80%) in Group 1 and 11 (64.7%) in Group 2 achieved
complete obliteration. The only patient in Group 3 did not achieve obliteration.
Complications included brainstem edema (n = 1) and transient pulmonary edema (n =
1). Four patients experienced hemorrhaging episodes, 30, 40, 84, and 96 months
after radiosurgery. Multivariate logistic regression analysis demonstrated that
only volume was significantly correlated with obliteration rates (P = 0.0109).
CONCLUSION: Radiosurgery is safe and efficacious for selected children with AVMs.
The obliteration rates and the attendant low morbidity rates suggest a primary
role for stereotactic radiosurgery for pediatric AVMs.
PMID- 11014421
TI - Management outcomes for ruptured and unruptured aneurysms in the elderly.
AB - OBJECTIVE: In a patient older than 70 years, the decision to treat an
intracranial aneurysm remains difficult whether it is ruptured or unruptured. We
sought to review our institutional risks of treatment of such lesions in the
context of the risks of rupture and its associated morbidity and mortality in
this age group. METHODS: One hundred twenty-nine consecutive patients aged 70
years or older, who were treated at a single institution for an intracranial
aneurysm, were retrospectively reviewed. Forty patients were treated for
unruptured aneurysms, and 89 patients presented after subarachnoid hemorrhage.
Seven additional patients in this age group who had solely intracavernous
lesions, as well as one patient with a dolichoectatic fusiform basilar lesion,
were excluded. Management outcomes were assessed using a modification of the
Glasgow Outcome Scale, and additional physical and functional disability was
assessed using the Barthel index and the Reintegration to Normal Living index.
RESULTS: Six-month outcomes for the unruptured group were: excellent, 70%; good,
15%; fair, 5%; poor, 7.5%; and death (2.5%). Outcomes for all patients with
ruptured lesions (including those not offered aggressive therapy) were:
excellent, 34%; good, 9%; fair, 5.6%; poor, 3.4%; and death, 45%. Long-term
follow-up was performed by questionnaire to assess physical and functional
disability. Although physical disability (Barthel index) was similar among
survivors, the Reintegration to Normal Living index, a global assessment of
function, was significantly higher in patients with unruptured aneurysms (84.8
versus 70.1; P = 0.05), which highlights the disabling effects of hemorrhage.
CONCLUSION: On the basis of an individual treatment center's management risks,
annual aneurysmal rupture rates can be estimated that justify treatment in this
difficult patient population. Despite recent controversy regarding aneurysmal
hemorrhage rates, we think that symptomatic unruptured aneurysms should be
treated and good results can be achieved, even in older patients.
PMID- 11014424
TI - Hyperthermia in the neurosurgical intensive care unit.
AB - OBJECTIVE: In patients with traumatic or ischemic brain injury, hyperthermia is
thought to worsen the neurological injury. We studied fever in the neurosurgical
intensive care unit (ICU) population using a definition common to surgical
practice (rectal temperature >38.5 degrees C). We sought to determine fever
incidence, fever duration, and peak temperature and to quantify the use of
antipyretic therapy. We also attempted to determine the patient subgroups that
are at highest risk for development of fever. METHODS: In a retrospective chart
review of a 6-month period, all febrile episodes that occurred in a consecutive
series of neurosurgical ICU patients in a university hospital setting were
studied. A febrile episode was defined as a rectal temperature of at least 38.5
degrees C; an episode lasted until the temperature fell below this threshold.
RESULTS: The 428 patients studied had 946 febrile episodes. Fever occurred in 47%
of patients, with a mean of 4.7 febrile episodes in each febrile patient. Fevers
occurred in more than 50% of patients who were admitted to the ICU for
subarachnoid hemorrhage, a central nervous system infection, seizure control, or
hemorrhagic stroke, but they occurred in only 27% of patients admitted for spinal
disorders. Fevers occurred in 15% of the patients who stayed in the ICU less than
24 hours, but in 93% of those who remained longer than 14 days. Despite the use
of antipyretic therapy for 86% of the febrile episodes, 57% lasted longer than 4
hours and 5% lasted longer than 12 hours. CONCLUSION: Fever is common in
critically ill neurosurgical patients, especially those with a prolonged length
of stay in the ICU or a cranial disease. If hyperthermia worsens the functional
outcome after a primary ischemic or traumatic injury, as has been suggested by
several studies of stroke patients, treatment of fever is a clinical issue that
requires better management.
PMID- 11014423
TI - Surgical treatment of clinically nonsecreting pituitary adenomas in elderly
patients.
AB - OBJECTIVE: The goal of this study was to evaluate the efficacy and safety of
transsphenoidal pituitary surgery for elderly patients, using improved techniques
of the past decade. METHODS: We retrospectively analyzed 32 surgically treated
cases of clinically nonsecreting pituitary adenomas in patients more than 70
years of age (mean, 73.9+/-3.4 yr). These patients were identified in a review of
982 patients with pituitary adenomas who were treated at University Hospital
Eppendorf, Hamburg, between January 1991 and November 1999. RESULTS: The mean
preoperative duration of symptoms was 1.9 years (2 wk to 11 yr). The chiasmatic
syndrome was present for 27 patients (84.4%). All patients underwent
transsphenoidal surgery. Seven patients underwent reoperations. Preoperative
assessments of anterior pituitary function revealed growth hormone deficiencies
for 21 of 27 patients (77.8%), thyroid insufficiencies for 10 of 30 patients
(33.3%), and adrenal insufficiencies for 13 of 29 patients (44.8%). Hypogonadism
and hyperprolactinemia were observed for 76.7% and 46.9% of the patients,
respectively. All tumors were macroadenomas, ranging from 18 to 50 mm (average,
33.6 mm) in size, including 7 enclosed and 25 invasive adenomas. Complete
microscopic tumor resection was achieved in 24 cases, and subtotal removal was
performed in 8 cases. There were no severe perioperative complications. In the
cases involving hyperprolactinemia, serum prolactin levels were normalized for 8
of 11 patients (72.7%). Normal thyroid function was recovered for 1 of 10
patients (10.0%) with preoperative hypothyroidism. However, growth hormone or
adrenal insufficiencies persisted for all patients with preoperative
insufficiencies. Visual disturbances were improved for 19 of 23 patients (82.6%).
All patients recovered well after surgery, with an average hospital stay of 16.3
days. Histological and immunohistochemical studies demonstrated gonadotroph
adenomas in 56.7% of cases, null-cell adenomas in 26.7%, and oncocytomas in
13.3%. CONCLUSION: Surgical treatment of nonsecreting pituitary adenomas causing
visual disturbances is standard, even for elderly patients. In this series,
transsphenoidal surgery was a safe procedure, with minimal morbidity and
excellent tolerance. Age alone is not a contraindication for active treatment,
particularly with transsphenoidal surgery.
PMID- 11014425
TI - Craniopharyngiomas of the third ventricle: trans-lamina terminalis approach.
AB - OBJECTIVE: Craniopharyngiomas usually grow on the cisternal surface of the
hypothalamic region; these tumors can also grow from the infundibulum or tuber
cinereum on the floor of the third ventricle, developing exclusively into the
third ventricle. The aim of the present work was to establish the usefulness of
the pterional trans-lamina terminalis approach for the removal of these tumors.
METHODS: Eight patients who were surgically treated for craniopharyngiomas
located exclusively within the third ventricle were considered. The initial
symptoms were acute hydrocephalus in two cases, psychological disturbances in
two, amenorrhea in two, headaches in one, and hypopituitarism in one. The
diagnoses were established, in all cases except one, with magnetic resonance
imaging. In all cases, the tumor completely filled the third ventricle. RESULTS:
Total removal of the lesion was achieved in seven cases. One patient underwent
partial removal. In the immediate postoperative period, no major complications
were observed. Five patients required replacement hormonal therapy. All patients
returned to a normal life. Many months after surgery, two patients exhibited
psychological disturbances and died, the first because of voluntary withdrawal of
replacement therapy (12 mo after surgery) and the second because of a severe
imbalance in body fluids and electrolytes, with a subsequent hyperosmolar coma
(27 mo after surgery). Only one patient who underwent initial total removal
experienced a small recurrence of the lesion (30 mo after surgery); after 3
years, the lesion exhibited unchanged size. CONCLUSION: In our experience, the
trans-lamina terminalis approach is a valid choice for the removal of purely
intraventricular craniopharyngiomas. These tumors can be removed without
significant sequelae related to the surgical approach. The proximity to the
hypothalamus requires accurate neuroendocrine and electrolyte control in the
postoperative period, in some cases even years after surgery.
PMID- 11014426
TI - Three-dimensional reconstructed images after rotational angiography in the
evaluation of intracranial aneurysms: surgical correlation.
AB - OBJECTIVE: To evaluate the diagnostic accuracy of three-dimensional reconstructed
images from rotational digital subtraction angiography in the surgical treatment
of intracranial aneurysms. METHODS: Twenty-two patients with 34 intracranial
aneurysms underwent biplane angiography (40 degrees per s, 4.5 degrees per image,
8.8 frames per s). Three-dimensional (3-D) reconstructed images were obtained at
a separate Advantage 3.1 workstation (General Electric, Milwaukee, WI) after the
rotational images were transferred. The available visualization techniques
included maximum intensity projection, shaded surface display, and virtual
endoluminal view. All images were evaluated in correlation with intrasurgical
visual data recorded on digital videotapes. RESULTS: 3-D reconstructed images
correlated well with surgical findings. The shape of the aneurysms, their neck
size, and their relationships to the parent vessels and other branches were
depicted clearly, especially compared with images obtained by two-dimensional
conventional digital subtraction angiography and magnetic resonance angiography.
CONCLUSION: 3-D digital subtraction angiography enables the surgeon to understand
the 3-D structure of lesions and is very useful in planning the surgical
treatment of cerebral aneurysms.
PMID- 11014427
TI - Computer-assisted fluoroscopic targeting system for pedicle screw insertion.
AB - OBJECTIVE: Biplanar fluoroscopic imaging linked to a computer-driven mechanical
end-effector is under development as a targeting system for spinal surgery. This
technology has the potential to enhance standard intraoperative fluoroscopic
information for localization of the pedicle entry point and trajectory, and it
may be an effective alternative to the computed tomography-based image-guided
system (IGS) in pedicle screw placement. A preclinical study to assess the
accuracy and time efficiency of this system versus a conventional IGS was
conducted. METHODS: Pedicle screw placement was performed in six cadavers from T1
to S1 levels using the ViewPoint IGS (Picker International, Inc., Cleveland, OH)
on one side versus the Fluorotactic guidance system (Z-Kat, Inc., Miami, FL) on
the other side. Of 216 possible pedicles, 208 were instrumented; 8 pedicle
diameters were too small or were not adequately imaged. Postinsertion, each
pedicle was assessed for the presence and location of cortical perforation using
computed tomographic scanning and direct visualization. RESULTS: The number of
successful screw placements was 89 (87.3%) of 102 for IGS and 87 (82.1 %) of 106
for the Fluorotactic guidance system, respectively. The mean time to register and
operate on one level using the Fluorotactic guidance system was 14:34 minutes
(minutes:seconds), compared with 6:50 minutes using the IGS. The average
fluoroscope time was 4.6 seconds per pedicle. CONCLUSION: Our data indicate that
this first-generation fluoroscopy-based targeting system can significantly assist
the surgeon in pedicle screw placement. The overall accuracy is comparable to an
IGS, especially in the region of T9-L5. A second-generation system with a faster
end-effector and user-friendly interface should significantly reduce the
operating and fluoroscope time.
PMID- 11014428
TI - Correlation of neurosurgical subspecialization with outcomes in children with
malignant brain tumors.
AB - OBJECTIVE: This study was performed to evaluate the association between the type
of neurosurgeon (general or pediatric) and either the extent of tumor removal or
the frequency of complications in children undergoing malignant brain tumor
resections. METHODS: Data were analyzed from three recent Children's Cancer Group
studies: two on medulloblastomas/primitive neuroectodermal tumors and one on
malignant gliomas. Neurosurgeons were classified as general neurosurgeons, as
designated pediatric neurosurgeons in their institutions, or as members of the
American Society of Pediatric Neurosurgeons (ASPN), which requires pediatric
neurosurgical experience and practice standards. RESULTS: Data forms from 732
children were analyzed; 485 were from children with medulloblastomas/primitive
neuroectodermal tumors, and 247 were from children with malignant gliomas.
Operations were performed by 269 neurosurgeons, including 213 general
neurosurgeons, 29 designated pediatric neurosurgeons, and 27 ASPN members. The
mean number of operations per surgeon was 1.8, 4.9, and 7.6 for general
neurosurgeons, designated pediatric neurosurgeons, and ASPN members,
respectively. There was a significant relationship between the extent of tumor
resection or the amount of residual tumor and the type of neurosurgeon.
Designated pediatric neurosurgeons and ASPN members were more likely to remove
more than 90% of the tumor and to leave less than 1.5 cc of residual tumor than
were general neurosurgeons (P<0.05). In these studies, the probability of
extensive tumor removal correlated with the number of operations the neurosurgeon
performed (P<0.01). Neurological complications occurred in the following
proportion of cases: general neurosurgeons, 23%; designated pediatric
neurosurgeons, 32%; and ASPN members, 18%. CONCLUSION: Pediatric neurosurgeons
are more likely than general neurosurgeons to extensively remove malignant
pediatric brain tumors. In these tumors, extent of removal has been demonstrated
to influence survival.
PMID- 11014429
TI - Molecular insight into medulloblastoma and central nervous system primitive
neuroectodermal tumor biology from hereditary syndromes: a review.
AB - Through the study of uncommon familial syndromes, physicians and scientists have
been able to illuminate the underlying mechanisms of some of the more common
sporadic diseases; this is illustrated best by studies of familial
retinoblastoma. A number of rare familial syndromes have been described in which
affected individuals are at increased risk of developing medulloblastoma and/or
supratentorial primitive neuroectodermal tumors. The descriptions of many of
these syndromes are based on patients observed by clinicians in their clinical
practice. Determination of the underlying genetic defects in these patients with
uncommon syndromes has led to identification of a number of genes subsequently
found to be mutated in sporadic medulloblastomas (tumor suppressor genes).
Associated genes in the same signaling pathways have also been found to be
abnormal in sporadic medulloblastoma. Identification of patients with these rare
syndromes is important, as they are often at increased risk for additional
neoplasms, as are family members and future children. We review the published
literature describing hereditary syndromes that have been associated with an
increased incidence of medulloblastoma and/or central nervous system primitive
neuroectodermal tumor. Review of the underlying molecular abnormalities in
comparison to changes found in sporadic neoplasms suggests pathways important for
tumorigenesis.
PMID- 11014430
TI - Liliequist's membrane is a fold of the arachnoid mater: study using sheet
plastination and scanning electron microscopy.
AB - OBJECTIVE: The subarachnoid space consists of a number of distinct subarachnoid
cisterns. They are separated from each other by trabecular walls, one of which is
Liliequist's membrane. The aim of this study was to investigate the anatomic
characteristics of Liliequist's membrane. METHODS: The study used a combined
approach, consisting of the modified E12 sheet plastination method for 3 adult
cadavers and gross anatomic dissection for 35 cadavers, 2 of which were further
examined using scanning electron microscopy. RESULTS: The results from this study
indicate that 1) Liliequist's membrane is an avascular fold of the arachnoid
mater that lacks openings and spreads out laterally, being in direct continuity
with the arachnoid mater covering the tentorium; 2) the carotid-chiasmatic walls,
which separate the chiasmatic cistern and carotid cisterns and had been
considered to be parts of Liliequist's membrane, are vascular and incomplete
trabecular walls and should not be considered parts of Liliequist's membrane;
and, 3) as a fold of the arachnoid mater, Liliequist's membrane is not directly
attached to the temporal lobes and oculomotor nerves. CONCLUSION: Liliequist's
membrane is a double-layer fold of the arachnoid mater and has anatomic
characteristics different from those of arachnoid trabecular walls.
PMID- 11014431
TI - Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor
expression in human cerebral arteriovenous malformations.
AB - OBJECTIVE: Human cerebral arteriovenous malformations (AVMs) are speculated to
result from abnormal angiogenesis. Vascular endothelial growth factor receptors
(VEGF-Rs) and Tie-2 play critical roles in vasculogenesis and angiogenesis. We
hypothesized that the abnormal vascular phenotype of AVMs may be associated with
abnormal expression of VEGF-Rs and Tie-2. METHODS: We measured the expression of
Tie-2, VEGF-R1, and VEGF-R2 in AVMs and normal brain tissue, using
immunoblotting. To assess active vascular remodeling, we also measured
endothelial nitric oxide synthase expression. CD31 expression was used to control
for endothelial cell mass for Tie-2, VEGF-Rs, and endothelial nitric oxide
synthase. Immunoblotting data were presented as relative expression, using normal
brain tissue values as 100%. RESULTS: CD31 was expressed to similar degrees in
AVMs and normal brain tissue (99+/-29% versus 100+/-20%, mean +/- standard error,
P = 0.98). Tie-2 expression was markedly decreased in all AVMs, compared with
normal brain tissue (16+/-9% versus 100+/-37%, P = 0.04). VEGF-R1 expression was
decreased in four of five AVMs, but the difference between the mean values was
not significant (35+/-8% versus 100+/-42%, P = 0.14). VEGF-R2 expression was
decreased in all AVMs, compared with normal brain tissue (28+/-6% versus 100+/
29%, P = 0.03). There was no difference in endothelial nitric oxide synthase
expression between AVMs and normal brain tissue (106+/-42% versus 100+/-25%, P =
0.91). CONCLUSION: AVM vessels exhibited abnormal expression of Tie-2 and VEGF
Rs, both of which may contribute to the pathogenesis of AVMs.
PMID- 11014432
TI - Vascular endothelial growth factor-driven glioma growth and vascularization in an
orthotopic rat model monitored by magnetic resonance imaging.
AB - OBJECTIVE: The goal of the present study was to develop an orthotopic in vivo
model for the investigation of vascular endothelial growth factor (VEGF)
dependent glioma growth and vascularization. METHODS: C6 glioma cells were
infected with viruses encoding sense or antisense VEGF. Expression of the
transgene was controlled by Northern blot analysis, Western blot analysis, and
immunohistochemistry. Spheroids generated from both clones as well as from wild
type and mock-transfected cells were implanted in the brains of Sprague-Dawley
rats. Growth and vascularization were assessed using magnetic resonance imaging
after 7 and 11 days. Histology was studied using hematoxylin and eosin staining,
immunohistochemistry with anti-von Willebrand staining, anti-VEGF, anti-CD8, and
assessment of vessel density. RESULTS: Cell proliferation, migration, and
invasion in vitro were very similar in all cell clones. Sense gliomas
demonstrated by far the fastest growth in vivo, with intense contrast enhancement
meeting criteria for highly malignant tumors. Histological examination revealed
masses of von Willebrand- and VEGF-positive tumor vessels with a high vessel
density. Antisense gliomas depicted the radiological features of low-grade
gliomas, with slow growth and poor vascularization, although they were highly
infiltrative. Wild-type and mock-transfected gliomas demonstrated similar growth
and vascularization patterns intermediate between sense and antisense gliomas.
Any influence of the allogeneic response of the hosts on different tumor sizes
could be excluded. CONCLUSION: Our model elucidates glioma growth and
vascularization as strongly VEGF dependent, which is consistent with human
gliomas. Thus, this model is suitable for testing antiangiogenic strategies to
interfere with the VEGF/VEGF receptor system, as well as for exploring VEGF
independent mechanisms using the antisense-transfected clone.
PMID- 11014434
TI - Preconquest Peruvian neurosurgeons: a study of Inca and pre-Columbian
trephination and the art of medicine in ancient Peru.
AB - Trephination and craniotomy performed by abrasion, scraping, crosscut sawing, and
drilling are the oldest known surgical techniques used by primitive peoples. As a
result of archaeological findings, the human skull is the most frequently studied
part of the excavated body, leading to the creation of a new aspect of
anthropology known as "cultural osteology." Found in ancient tombs, the human
remains, mummies, skeletons, and their belongings, including war instruments,
pottery, clothing, jewels, and surgical instruments, constitute the richest
source of insight into the lives and pragmatic activities of ancient cultures.
This study summarizes thousands of years of pre-Columbian history and medical
evolution, specifically in the early and primitive practice of trephination, as
precursors of neurosurgery. Comparative osteology studies have demonstrated that
using primitive stone or metal instruments, the sirkaks (Inca surgeons) achieved
an average survival rate of 50 to 70% of their craniectomy patients, with little
incidence of infection or other complications. Despite their rudimentary
knowledge of disease and pathology, a considerable knowledge of anatomy and
natural medicine provided them with hemostatic agents, antiseptics, and other
medical drugs, such as quinine for fever and malaria, as well as gold, silver,
and other products to perform cranioplasties. Living in a world of continuous
hand-to-hand combat, they also developed aggressive and defensive weapons that
necessitated refinement of surgical techniques to save soldiers from battle
wounds to their poorly protected crania.
PMID- 11014433
TI - Combined antitumor effects of an adenoviral cytosine deaminase/thymidine kinase
fusion gene in rat C6 glioma.
AB - OBJECTIVE: In this study, we investigated the feasibility of a double-suicide
gene/prodrug therapy, involving direct introduction of the herpes simplex virus
Type 1 thymidine kinase (TK) gene and the Escherichia coli cytosine deaminase
(CD) gene, via a recombinant adenoviral vector, and ganciclovir (GCV) and/or 5
fluorocytosine (5-FC) treatment, in a rat C6 glioma model. METHODS: Efficient
gene transfer and transduction of C6 glioma cells via a recombinant adenovirus
were evaluated by infecting cells with adenovirus bearing the beta-galactosidase
gene and then staining cells with X-5-bromo-4-chloro-3-indolyl-13-D-galactoside.
CD/TK expression in cells infected with adenovirus bearing the CD/TK gene (ad
CD/TK) was examined by immunoblotting analysis. For in vitro cytotoxicity
experiments, the cells were infected with ad-CD/TK or ad-deltaE1 (as a control).
After the addition of a variety of concentrations of GCV and 5-FC, either
separately or in combination, cell viability was determined by staining the cells
with crystal violet solution 6 days after infection. For in vivo antitumor
experiments, 1x10(5) cells were stereotactically injected into the right caudate
putamen of female Wistar rat brains. At 3 days after implantation, 1x10(8) plaque
forming units of ad-CD/TK or ad-deltaE1 (as a control) were stereotactically
injected into the tumors and GCV (25 mg/kg) and 5-FC (250 mg/kg), alone or in
combination, were intraperitoneally administered. Animals were then killed, and
tumor volumes were measured by determining the tumor area in every fifth section,
using a light microscope. RESULTS: C6 glioma cells were efficiently transduced
with recombinant adenoviral vector at multiplicities of infection of 200 or more.
In vitro cytotoxicity of GCV and/or 5-FC, either alone or in combination, was
exclusively observed in the cells transduced with ad-CD/TK. Obvious cytotoxicity
(>50% inhibition) was observed in the presence of 5-FC at concentrations greater
than 30 microg/ml or GCV at concentrations greater than 0.3 microg/ml at a
multiplicity of infection of 100. Additionally, cytotoxicity in the presence of
both GCV and 5-FC was greater than that after single-prodrug treatments,
indicating additive effects of the prodrug treatments. In in vivo experiments,
the tumor volumes of the rats treated with GCV or 5-FC alone after ad-CD/TK
injection (59.1+/-4.6 and 57.4+/-7.1 mm3, respectively) were significantly
smaller than that of the control rats (157+/-8.9 mm3, P<0.05). Furthermore, the
tumor volume of the rats treated with GCV and 5-FC in combination was 14.7+/-1.8
mm3. CONCLUSION: These results demonstrated the efficient transduction of C6
glioma cells with a recombinant adenovirus and the additive effects of CD/TK
fusion gene/GCV/5-FC treatment, compared with single-gene therapy with the TK or
CD gene. Therefore, our data suggest that the direct administration of a double
suicide gene/prodrug therapy has great potential in the treatment of brain
tumors.
PMID- 11014435
TI - Color illustrations and neurosurgical techniques of Serefeddin Sabuncuoglu in the
15th century.
AB - Serefeddin Sabuncuoglu (AD 1385-1468?) is the author of Cerrahiyyetu'l-Haniyye
(Imperial Surgery), which was written in Turkish in 1465. It was the first
illustrated textbook of surgery in the Turkish medical literature, containing
color illustrations of surgical procedures, incisions, and instruments.
Sabuncuoglu, a pioneer of surgery, developed numerous original techniques in a
variety of surgical specialties. He described surgical management of spinal
trauma, epilepsy, migraine, facial palsy, hemiplegia, low back pain, cranial
fracture, and hydrocephalus. The aim of this study is to describe his
contributions to neurosurgery.
PMID- 11014436
TI - Sclerosing epithelioid fibrosarcomas involving the neuraxis: report of three
cases.
AB - OBJECTIVE AND IMPORTANCE: Sclerosing epithelioid fibrosarcoma (SEF) is a rare
mesenchymal neoplasm composed of rounded, vimentin-immunoreactive tumor cells
disposed in nests and cords within a hyalinized collagenous matrix. Most examples
arise in the deep skeletal muscles of adults. The cases recorded to date have
been characterized by protracted clinical evolutions with a tendency for stubborn
local recurrence, followed by late metastasis. Accordingly, SEF has been regarded
as a low-grade sarcoma. A single instance of brain and vertebral metastasis has
been described. We report three examples of SEF distinguished by primary
involvement of the neuraxis at initial presentation. CLINICAL PRESENTATION: Two
tumors had intracranial, calvarial and extracalvarial, soft-tissue components,
whereas the third tumor manifested as a paraspinal mass with extension into the
T12-L1 neural foramen and invasion of the T12 nerve root. INTERVENTION: All three
affected patients experienced local recurrence and distant metastasis after
resection of the primary site. These complications appeared early in the disease
course in two cases. In no case was there a response to adjuvant chemotherapy or
radiotherapy. CONCLUSION: Our experience indicates that SEFs arising along the
neuraxis may demonstrate unexpectedly aggressive clinical behavior, compared with
those arising in the more typical location of deep skeletal muscles.
PMID- 11014437
TI - Intravascular papillary endothelial hyperplasia arising within a posteroinferior
cerebellar artery aneurysm: case report and review of the literature.
AB - OBJECTIVE AND IMPORTANCE: Intravascular papillary endothelial hyperplasia (IPEH)
is an atypical proliferation of endothelium that results in abnormal organization
for thrombus formation. Intracranial IPEH is a rare entity and has not been
reported to arise from within an intracranial aneurysm. Furthermore, the elapsed
time during which acquired intracranial IPEH develops has not been previously
documented. CLINICAL PRESENTATION: In this case report, a patient with facial and
neck pain was noted to have an enhancing mass lesion lateral to the medulla in
magnetic resonance imaging scans. Angiography revealed a vascular mass adjacent
to the posteroinferior cerebellar artery. Normal magnetic resonance imaging and
magnetic resonance angiographic findings had been obtained for the patient 29
months earlier. INTERVENTION: During surgery, a thrombosed, 2.5-cm,
posteroinferior cerebellar artery aneurysm was resected and noted to contain
florid IPEH. There has been no evidence of recurrence in 1 year of follow-up
monitoring. A literature search revealed 13 cases of intracranial IPEH, in which
recurrence was observed for incompletely resected lesions. CONCLUSION: IPEH can
develop in a relatively short time, can present as a hypervascular mass lesion or
within an intracranial aneurysm, and should be completely resected to prevent
recurrence.
PMID- 11014438
TI - Bilateral cerebellopontine angle arachnoid cysts: case report.
AB - OBJECTIVE AND IMPORTANCE: A rare case of bilateral cerebellopontine angle (CPA)
arachnoid cysts (ACs), accompanied by cerebellar tonsillar displacement toward
the foramen magnum, is presented. CLINICAL PRESENTATION: A 45-year-old woman
presented with progressive dysphagia, vertigo, and truncal ataxia. Magnetic
resonance imaging revealed bilateral CPA ACs and cerebellar tonsillar
displacement. INTERVENTION: The right CPA AC was excised via a suboccipital
approach. Decompression of the foramen magnum and duraplasty were also performed.
CONCLUSION: The case reported here is the first case of bilateral CPA ACs.
Decompression of the foramen magnum and excision of the cyst resulted in complete
relief of symptoms.
PMID- 11014439
TI - Tuberculosis of the axis in a patient with systemic sarcoidosis: technique of
posterior open biopsy of the dens: case report.
AB - OBJECTIVE AND IMPORTANCE: This case report illustrates the importance of
obtaining tissue from a destructive lesion of the dens in a patient with systemic
sarcoidosis. Although sarcoidosis can involve the axial skeleton, tissue obtained
at the time of C1-C2 fusion demonstrated unsuspected pathological features, which
dramatically altered the subsequent medical treatment. The technique of open
posterior biopsy of the dens is illustrated, and the advantages of the approach
are discussed. CLINICAL PRESENTATION: A 40-year-old woman with systemic
sarcoidosis developed neck pain and atlantoaxial instability. Imaging revealed
multiple thoracic and cervical vertebral abnormalities, including a destructive
enhancing lesion involving the base of the dens. INTERVENTION: At the time of
posterior C1-C2 fusion, we elected to perform an open biopsy of the base of the
dens. A 16-gauge biopsy needle was introduced along the medial portion of the
left C2 pars, aiming medially toward the base of the odontoid process. This
procedure was performed under direct observation, with fluoroscopic guidance. The
biopsy specimen contained caseating granulomas, and cultures were positive for
Mycobacterium tuberculosis. CONCLUSION: The unusual presentation, the technique,
and the importance of obtaining tissue to confirm the diagnosis of tuberculous
involvement of the dens are emphasized. The relationship between sarcoidosis and
tuberculosis reported in the literature is reviewed. In the current case, cell
wall-positive tuberculous bacteria were cultured, confirming the presence of two
separate diseases in the same patient.
PMID- 11014440
TI - Candida albicans cerebral granulomas associated with a nonfunctional
cerebrospinal fluid shunt: case report.
AB - OBJECTIVE AND IMPORTANCE: We report an unusual case of basal ganglia granulomas
caused by Candida albicans that surrounded the proximal segment of a
nonfunctional cerebrospinal fluid shunt in a previously healthy patient. CLINICAL
PRESENTATION: A 22-year-old woman had undergone ventriculoatrial cerebrospinal
fluid shunt placement for posttraumatic hydrocephalus 3 years previously. One
year later, a shunt revision was followed by wound dehiscence with local
infection at the neck level. She received oral administration of antibiotics for
3 months until the wound closed. Twelve weeks before admission, the patient
experienced pulmonary emboli. She received anticoagulants, and the distal segment
of the shunt was removed. Five weeks after shunt removal, she presented with
headache and left-sided hemiplegia caused by right basal ganglia inflammatory
masses. INTERVENTION: A stereotactic brain biopsy was performed, and the shunt
remnants were removed. Microscopically, the lesions were acutely and chronically
inflamed. C. albicans grew in tissue and in shunt hardware cultures. The patient
was treated with 1.1 g of intravenously administered amphotericin B and orally
administered ketoconazole; she recovered completely. CONCLUSION: C. albicans
brain granulomas occur rarely in immunocompetent patients. Despite the large size
of the lesions and severe brain edema, the absence of an underlying disease
contributed to complete resolution after shunt removal and antifungal therapy.
PMID- 11014441
TI - Chronic hydrocephalus presenting with bilateral ptosis after minor head injury:
case report.
AB - OBJECTIVE AND IMPORTANCE: Some patients with hydrocephalus may exhibit various
signs of oculomotor dysfunction. However, ptosis has not previously been
described in chronic hydrocephalus patients. CLINICAL PRESENTATION: We report a
50-year-old woman who was diagnosed with chronic hydrocephalus based on an
evaluation for bilateral ptosis after a minor head injury. She exhibited
bilateral ptosis and upward gaze paralysis, but other oculomotor functions were
normal. Neuroimages revealed chronic hydrocephalus with no traumatic
abnormalities. INTERVENTION: The eyelid dysfunction resolved after placement of a
right ventriculoperitoneal shunt with a programmable pressure valve. CONCLUSION:
The resolution of eyelid dysfunction by cerebrospinal fluid diversion suggests
that chronic hydrocephalus was involved in the development of ptosis after the
minor head injury. A mild but sudden cerebrospinal fluid pressure change at the
time of minor head injury might induce functional impairment at the level of
vulnerable periaqueductal structures, which barely withstood the longstanding
ventriculomegaly, resulting in the clinical features observed in our patient.
PMID- 11014442
TI - Carotid stenting and "extarterectomy" in the management of head and neck cancer
involving the internal carotid artery: technical case report.
AB - OBJECTIVE AND IMPORTANCE: Head and neck cancer that invades the internal carotid
artery (ICA) represents a significant management challenge. We describe a novel
technique that allows for aggressive tumor removal without disrupting blood flow
through the affected ICA. CLINICAL PRESENTATION: A 62-year-old man was referred
to our institution for management of a neck malignancy involving the ICA.
Cerebral angiography suggested that there was good collateral flow from the
opposite hemisphere, but the patient reported visual loss in the ipsilateral eye
during balloon test occlusion of the ICA. INTERVENTION: A self-expanding stent
was deployed in the ICA; it spanned the entire length of the artery involved by
tumor. One month later, the patient underwent tumor resection. During surgery, a
long ICA arteriotomy was performed directly down to the mesh of the stent. A
neoendothelium had formed within the stent, which prevented arterial bleeding.
The carotid wall was dissected from the stent without difficulty and removed en
bloc with the surrounding tumor. The exposed stent was wrapped circumferentially
with a synthetic patch material. The patient tolerated the procedure well, and
postoperative angiography demonstrated normal filling of the ICA. CONCLUSION: We
describe a novel approach to a patient with head and neck cancer involving the
cervical ICA. Preliminary stenting, which allows time for endothelialization
before surgery, may permit aggressive tumor resection without interrupting flow
through the ICA. This technique obviates the need for complicated carotid
reconstruction procedures and avoids the risk of delayed ischemia from carotid
sacrifice.
PMID- 11014443
TI - Modified malis bayonet forceps aids application of the cyberonics vagus nerve
stimulator electrode: technical note.
AB - OBJECTIVE: To notify neurosurgeons about a modified bayonet forceps that aids
application of the vagus nerve stimulating electrode. METHODS: The manufacturer
(Codman & Shurtleff, Inc., Raynham, MA) extended the tips of an upward-angled
Malis bayonet forceps from 2 mm to 6 mm. RESULTS: The modified bayonet tips, when
placed under the vagus nerve, extend well beyond the edge of the usual vagus
nerve to easily accept the electrode lead. CONCLUSION: The modified bayonet
forceps and depicted wrapping sequence shorten electrode wrapping time.
PMID- 11014444
TI - Limitations of the C6/Wistar rat intracerebral glioma model: implications for
evaluating immunotherapy.
AB - OBJECTIVE: Intracranial rat glioma models are a useful method for evaluating the
efficacy and toxicity of novel therapies for malignant glioma. The C6/Wistar
model has been used extensively as a reproducible in vivo model for studying
primary brain tumors including anti-glioma immune responses. The objective of the
present study is to provide in vivo evidence that the C6 rat glioma model is
allogeneic within Wistar rats and is therefore inappropriate for evaluating
immune responses. METHODS: Growth patterns and immune responses of C6 cells
implanted into the brain and flank of Wistar rats were analyzed and compared to
an immunogenic syngeneic model (9L/Fischer). RESULTS: Wistar rats with C6 tumors
developed a potent humoral and cellular immune response to the tumor. Wistar rats
given simultaneous flank and intracerebral tumors had a survival rate of 100%
compared to an 11% survival rate in control animals receiving only intracranial
C6 cells. CONCLUSION: The C6 rat glioma induces a vigorous immune reaction that
may mimic a specific anti-tumor response in Wistar rats. Efficacy of
immunotherapy within this model must be cautiously interpreted.
PMID- 11014445
TI - Stable isotope incorporation triples the upper mass limit for determination of
elemental composition by accurate mass measurement.
AB - By comparing electrospray ionization Fourier-transform ion cyclotron resonance
(FT-ICR) mass spectra and collision-induced dissociation (CID) FT-ICR mass
spectra of a phospholipid (851 Da) extracted from natural abundance and 99% 13C
bacterial growth media, we are able to reduce its number of possible elemental
compositions (based on +/-10 ppm externally calibrated mass accuracy and
biologically relevant compositional constraints) from 394 to 1. The basic idea is
simply that the mass of a molecule containing N carbon atoms increases by N Da
when 12C is replaced by 13C. Once the number of carbons is known, the number of
possible combinations of other atoms in the molecule is greatly reduced. We
demonstrate the method for a stored-waveform inverse Fourier transform-isolated
phospholipid from an extract of membrane lipids from Rhodococcus rhodochrous
hydrocarbon-degrading bacteria grown on either natural abundance or 99% 13C
enriched mixtures of n-hexadecane and n-octadecane. We project that this method
raises the upper mass limit for unique determination of elemental composition
from accurate mass measurement by a factor of at least 3, thereby extending
"chemical formula" determination to identification and sequencing of larger
synthetic and bio-polymers: phospholipids, oligopeptides of more than three to
four amino acids, DNA or RNA of more than two nucleotides, oligosaccharides of
more than three sugars, etc. The method can also be extended to determination of
the number of other atoms for which heavy isotopes are available (e.g., 15N, 34S,
18O, etc.).
PMID- 11014446
TI - Mass-correlated pulsed extraction: theoretical analysis and implementation with a
linear matrix-assisted laser desorption/ionization time of flight mass
spectrometer.
AB - The pulsed extraction (PE) of ions produced by matrix-assisted laser
desorption/ionization in time-of-flight mass spectrometers greatly improves mass
resolution but, unfortunately, this method is mass dependent. Here we report an
approach to expand the capabilities of the PE method so as to provide uniform
focusing conditions over a wide mass range. Along with an extraction pulse, an
additional pulse is applied to correct the mass dependency of the standard PE
method. We describe the algorithm for derivation of this correction pulse
waveform, where the first-order focusing conditions are valid all along the mass
region of interest. Experimental verification of this method for correction of
ion velocities demonstrated better mass resolution than standard PE over a wide
mass range.
PMID- 11014447
TI - Matrix-assisted laser desorption/ionization mass spectrometry methods for
oligodeoxynucleotides: improvements in matrix, detection limits, quantification,
and sequencing.
AB - A comatrix of anthranilic acid and nicotinic acid is optimum for the matrix
assisted laser desorption/ionization time of flight determination of
oligodeoxynucleotides that are comprised of up to 21 nucleotides. A detection
limit of approximately 200 amol was obtained for an oligonucleotide 21mer. The
comatrix system is also suitable for quantification of oligodeoxynucleotides
provided an internal standard having one more or less nucleotide than the number
in the analyte is used. Furthermore, the matrix, when used in combination with
the ladder method of sequencing, allows the complete sequence of tens of
picomoles of model oligodeoxynucleotides to be determined.
PMID- 11014448
TI - Selected ion flow tube mass spectrometry analyses of stable isotopes in water:
isotopic composition of H3O+ and H3O+ (H2O)3 ions in exchange reactions with
water vapor
AB - A new method has been developed for the determination of the isotope abundance
ratios of deuterium, D, and oxygen-18, 18O, in water vapor (and water) using
selected ion flow tube mass spectrometry (SIFT-MS). H3O+ ions are injected into
the helium carrier gas where they associate with the H2O and HDO molecules in a
sample of water introduced into the carrier gas. The D and 18O contents of the
product cluster ions H8DO4+ and H9(18)OO3+ at m/e = 74 and 75, respectively, are
determined by reference to the majority cluster ion H9O4+ at m/e = 73. Allowance
is made for the contribution of the H8(17)OO3+ ions to the m/z = 74 ions.
Absolute isotopic ratios are measured within seconds without the need for
precalibration of the SIFT-MS instrument, currently to an accuracy of better than
2%.
PMID- 11014450
TI - Evaluation of alkali metal binding selectivities of caged aza-crown ether ligands
by microelectrospray ionization/quadrupole ion trap mass spectrometry
AB - Microelectrospray ionization mass spectrometry (MESI-MS) is used to evaluate
alkali metal binding selectivities of a variety of macrocyclic compounds. Well
studied crown ethers are used to validate the MESI-MS method. A quantitative
correlation between MESI mass spectral ion intensities and solution equilibrium
distributions of complexes is obtained for the mixtures containing a single host
and different alkali metal guest ions. The MESI-MS method is successfully applied
for the determination of the alkali metal binding selectivities of a series of
cage-functionalized aza-crown ethers and relevant model compounds in methanol and
chloroform solutions. The binding selectivities parallel previous results
obtained using conventional spectrophotometric extraction methods. Structural
differences in the host compounds, such as the presence of a cage functionality,
binding cavity size, and overall flexibility, cause significant changes in the
binding selectivities.
PMID- 11014449
TI - A dual electrospray ionization source combined with hexapole accumulation to
achieve high mass accuracy of biopolymers in Fourier transform ion cyclotron
resonance mass spectrometry.
AB - A dual electrospray ionization (ESI) source employed with hexapole accumulation
and gated trapping provides a novel method of using an internal standard to
achieve high mass accuracies in Fourier transform ion cyclotron resonance mass
spectrometry. Two ESI emitters are sequentially positioned in front of the heated
metal capillary inlet by a solenoid fitted to an XYZ micromanipulator; one
emitter contains the analyte(s) of interest and the other an internal standard. A
5 V transistor-transistor logic pulse from the data station controls the solenoid
by means of a solid-state relay so that matching of spectral peak intensities
(i.e., analyte and internal standard intensities) can be accomplished by
adjusting the hexapole accumulation time for each species. Polythymidine,
d(pT)18, was used as the internal standard for all studies reported here. The
absolute average error for an internally calibrated 15-mer oligonucleotide
(theoretical monoisotopic mass = 4548.769 Da) was -1.1 ppm (external calibration:
41 ppm) with a standard deviation of +/-3.0 ppm (external calibration: +/-24 ppm)
for a total of 25 spectra obtained at various hexapole accumulation time ratios.
Linear least squares regression analysis was carried out and revealed a linear
dependence of the magnitudes of the peak height ratios (analyte/internal
standard) vs. hexapole accumulation time ratios (analyte/internal standard) which
is described by the following equation: y = 0.45 x - 0.02. The fitted line had a
%RSD of the slope of 28% with an R2 of 0.93. The applicability of this
methodology was extended to a polymerase chain reaction product with a
theoretical average molecular mass of 50,849.20 Da. With the internal standard,
d(pT)18, an absolute average error of -8.9 ppm (external calibration: 44 ppm)
based on five measurements was achieved with a standard deviation of 11 ppm
(external calibration: +/-36 ppm), thus illustrating this method's use for
characterizing large biomolecules such as those encountered in genomics and
proteomics related research.
PMID- 11014451
TI - Charge-remote and charge-driven fragmentation processes in diacyl
glycerophosphoethanolamine upon low-energy collisional activation: a mechanistic
proposal.
AB - A mechanistic study of diacyl glycerophosphoethanolamine fragmentation under low
energy collision-activated dissociation with electrospray ionization tandem mass
spectrometry is reported. The fragmentation pathways leading to the formation of
carboxylate anions (RxCO2-) (x = 1, 2) and the formation of the ions representing
neutral loss of ketene ([M - H - Rx'CH=C=O]-) are charge-driven processes, which
are governed by the gas-phase basicity and the steric configuration of the
molecules. The fragmentation pathway for the formation of the [M - H - RxCO2H]-
ions, reflecting neutral loss of fatty acid, is a charge-remote process, which
involves the participation of the hydrogens at C-1 and C-2 of the glycerol,
resulting in [M - H - R2CO2H]- > [M - H - R1CO2H]-. The preferential formations
of R2CO2- > R1CO2-, and of [M - H - R2'CH=C=O]- > [M - H - R1'CH=C=O]- are
attributed to the findings that charge-driven processes are sterically more
favorable at sn-2. The observation of the abundance of [M - H - Rx'CH=C=O]- > [M
H - RxCO2H]- is attributed to the fact that the [M - H]- ions of GPE are basic
precursor ions, which undergo preferential loss of ketene than loss of acid. The
major pathway for the formation of RxCO2- ions arises from the nucleophilic
attack of the anionic charge site of the phosphate on the C-1 or C-2 of the
glycerol to render a charge transfer. The sterically more favorable attack on the
C-2 than C-2 of the glycerol results in the abundance of R2CO2- > R1CO2-. These
features of tandem spectra readily identify and locate the fatty acid
substituents of GPE in the glycerol backbone.
PMID- 11014452
TI - Electrospray mass spectrometry and fragmentation of N-linked carbohydrates
derivatized at the reducing terminus.
AB - Derivatives were prepared from N-linked glycans by reductive amination from 2
aminobenzamide, 2-aminopyridine, 3-aminoquinoline, 2-aminoacridone, 4-amino-N-(2
diethylaminoethyl)benzamide, and the methyl, ethyl, and butyl esters of 4
aminobenzoic acid. Their electrospray and collision-induced dissociation (CID)
fragmentation spectra were examined with a Q-TOF mass spectrometer. The strongest
signals were obtained from the [M + Na]+ ions for all derivatives except sugars
derivatized with 4-amino-N-(2-diethylaminoethyl)benzamide which gave very strong
doubly charged [M + H + Na]2+ ions. The strongest [M + Na]+ ion signals were
obtained from the butyl ester of 4-aminobenzoic acid and the weakest from 2
aminopyridine. The most informative spectra were recorded from the [M + Li]+ or
[M + Na]+ ions. These spectra were dominated by ions produced by sequence
revealing glycosidic cleavages and "internal" fragments. Linkage-revealing cross
ring cleavage ions were reasonably abundant, particularly from high-mannose
glycans. Although the nature of the derivative was found to have little effect
upon the fragmentation pattern, 3-aminoquinoline derivatives gave marginally more
abundant cross-ring fragments than the other derivatives. [M + H]+ ions formed
only glycosidic fragments with few, if any, cross-ring cleavage ions. Doubly
charged molecular ions gave less informative spectra; singly charged fragments
were weak, and molecular ions containing hydrogen ([M + 2H]2+ and [M + H + Na]2+)
fragmented as the [M + H]+ singly charged ions with no significant cross-ring
cleavages.
PMID- 11014453
TI - Detection and quantification of the sulfated disaccharides in chondroitin sulfate
by electrospray tandem mass spectrometry.
AB - A new method of identifying and quantifying the disaccharide building blocks of
glycosaminoglycans is introduced. The polysaccharides are subjected to an
enzymatic digestion that releases the sulfated disaccharides. The disaccharides
are then identified using a combination of electrospray ionization mass
spectrometry and tandem mass spectrometry. Quantification of the isomeric
disaccharides is also achieved by tandem mass spectrometry, using a recently
developed methodology which quantifies mixtures of isomers without the use of
chromatography or prior separation. Using mass spectrometry to characterize the
components of glycosaminoglycans significantly reduces both sample consumption
and analysis time of traditional methods.
PMID- 11014454
TI - Review of the 48th ASMS conference on mass spectrometry and allied topics held in
Long Beach, California June 11-15, 2000
PMID- 11014455
TI - Taxonomy of pain.
AB - Research on the pathophysiology of chronic pain has begun to challenge the
traditional diagnostic and treatment paradigms for the patient with neuropathic
pain. The heterogeneous nature of neuropathic pain indicates that more than one
anatomic lesion is most likely responsible for the clinical presentation of a
particular syndrome. Numerous pharmacologic agents that have shown improved
efficacy in the treatment of neuropathic pain have been developed over the past
decade. For the practicing clinician, an important concern is whether the current
paradigm for classification of neuropathic pain syndromes is comprehensive enough
to address this rapidly expanding body of knowledge.
PMID- 11014456
TI - Chronic neuropathic pain: mechanisms and treatment.
AB - There have been considerable advances in our understanding of the pathophysiology
of neuropathic pain. There is still a lack of consensus about the optimal
therapeutic strategy of such conditions, however. Drugs are generally selected on
the basis of their established efficacy in randomized controlled studies in
etiologically based groups of patients. These studies have been important in
confirming the efficacy of antidepressants, antiepileptics, local anesthetics and
derivatives, capsaicin, opioids, and N-methyl-D-aspartate antagonists in
neuropathic pain, specifically painful diabetic neuropathy and postherpetic
neuralgia. More specific therapeutic strategies based on precise quantified
assessment of the various components of neuropathic pain are now increasingly
used and may provide insight regarding the effects of treatments of particular
symptoms (e.g., allodynia, hyperalgesia). In some cases, such assessment may also
help to analyze the mechanisms involved in pain, thus allowing selection of
treatment on a more rational basis. A mechanism-based approach seems promising
for clinical research studies, although its application in current management
remains challenging.
PMID- 11014457
TI - Neural mechanisms of cutaneous nociceptive pain.
AB - Acute mechanical, thermal, and chemically induced pains in the skin are signalled
by a set of specific nociceptive afferents, which encode the magnitude of the
perceived pain by their discharge intensity. After tissue injury or inflammation,
a number of changes in the properties of the primary afferent occur parallel to
profound changes in the central nervous system. Primary hyperalgesia (within the
area of tissue injury) is best explained by changes of the properties of primary
nociceptive afferents, whereas secondary hyperalgesia (increased pain sensitivity
outside the area of tissue injury) critically requires functional changes in the
central nervous system. Collectively, these changes are the basis for the many
forms of hyperalgesia that can present clinically as incident pain. Knowledge of
the various types of hyperalgesia and their underlying mechanisms is required for
better treatment of this challenging aspect of chronic pain.
PMID- 11014458
TI - A neuroimmune interaction in painful peripheral neuropathy.
AB - BACKGROUND: In almost every neuropathic pain state caused by peripheral nerve
damage, whether due to trauma or disease, both structural damage and an
inflammatory response exist. OBJECTIVE: The goal of this study was to determine
the contribution, separate from the effects of the structural lesion, of the
inflammatory response to neuropathic pain. METHODS: Two sets of experiments were
performed. In the first, an experimental inflammation of the nerve (a neuritis)
and an experimental inflammation of the muscle (a myositis control group) were
produced in two groups of rats. The pain responses to stimuli applied to the
sciatic nerve territory on the plantar hind paw were evaluated through tests of
(1) heat hyperalgesia; (2) mechanical allodynia; (3) mechanical hyperalgesia; and
(4) cold allodynia. In the second set of experiments, thalidomide or cyclosporin
A was used to block the production of immune modulators in the neuritis model and
in a chronic constriction injury model (which involves structural damage and an
inflammatory response in the sciatic nerve) to determine the contribution of the
immune response to the pain observed in the first set of experiments. RESULTS: In
experiment 1, rats with the neuritis but not those with the myositis developed
neuropathic pain symptoms. In experiment 2, thalidomide produced a partial but
significant reduction in pain in the chronic constriction injury model across all
four tests, but there was no effect in the neuritis model in any of the tests.
Cyclosporin-A resulted in a dose-related reduction in pain in both models across
all four tests. CONCLUSIONS: These data suggest the possibility of an important
interaction between the immune system and the nervous system in neuropathic pain
and suggest that drugs modulating the immune system may be useful therapies in at
least some neuropathic pain states.
PMID- 11014459
TI - Pain mechanisms and management: a central perspective.
AB - Although pain is always intense and unpleasant, the capacity to experience this
sensation is, under normal circumstances, fundamental to the preservation of
bodily integrity. Clinically, however, after injury to peripheral tissue or
directly to the nervous system, spontaneous and evoked pain manifest that serve
no physiologic function, are crippling to patients, and are difficult to treat.
Here, we review the specific role of the dorsal horn of the spinal cord in the
mechanisms of nociceptive protective pain and the spinal plasticity that occurs
after nerve and tissue injury. This spinal neuronal plasticity is shown to be a
key contributor to pathologic pain hypersensitivity. The potential for the
molecular mechanisms responsible for the spinal plasticity in revealing new
targets for future treatment is also discussed.
PMID- 11014460
TI - Expanded use of surfactant replacement therapy.
AB - There are a number of respiratory diseases affecting infants in which there is
surfactant dysfunction or deficiency. Surfactant is inactivated by cholesterol,
free fatty acids and bilirubin in meconium aspiration syndrome, by haemoglobin
and red blood cell lipids in pulmonary haemorrhage and plasma proteins are the
culprit in conditions associated with increased alveolar capillary permeability.
Surfactant production can be adversely affected by damage to the type 2
pneumocytes by viruses and neutrophil derived reactive oxygen metabolites. Not
surprisingly, therefore, the efficacy of exogenous surfactant has been tested,
usually in animal models and anecdotal series in "non respiratory distress
syndrome" respiratory disorders. Improvements in oxygenation have usually been
described. Relatively few randomized trials, however, have been performed, but
those undertaken have demonstrated longer term benefits. In term infants with
severe respiratory failure, surfactant administration significantly shortened the
duration of extracorporeal membrane oxygenation and, in those in the early phase
of severe respiratory failure or with meconium aspiration syndrome, it
significantly reduced the need for extracorporeal membrane oxygenation. In
meconium aspiration syndrome, a smaller number of surfactant treated patients
compared to controls developed airleaks. Surfactant administration was also
associated with a reduction in the duration of ventilation and intensive care
unit stay in patients with meconium aspiration syndrome or bronchiolitis. Those
data are very promising and should encourage studies to identify the optimum type
of surfactant, dosage regimen and administration method. CONCLUSION: Further
randomized trials are required to fully assess the efficacy and cost benefit
ratio of surfactant treatment in "non respiratory distress syndrome" respiratory
diseases.
PMID- 11014461
TI - Reye syndrome revisited: a descriptive term covering a group of heterogeneous
disorders.
AB - Reye syndrome, characterised by the combination of liver disease and
noninflammatory encephalopathy, is a non-specific clinicopathological entity and
a descriptive term covering a group of heterogeneous disorders. Nowadays, some of
these patients are diagnosed more correctly as having infectious, metabolic,
toxic or other disease. The non-specific case definition implies that the
epidemiological studies suggesting a link with acetylsalicylic acid have been
performed on a heterogeneous group of children, whereby the value of these
studies and their ensuing hypothesis is weakened. Moreover, a detailed analysis
of the epidemiological surveys of the Centers for Disease Control, the Yale study
and of the British risk factor study provides evidence that not only the use of
acetylsalicylic acid but also that of phenothiazines and other anti-emetics is
significantly greater in Reye syndrome cases than in controls. As to the decline
of Reye syndrome, recent literature data reveal that this is related to more
accurate modern diagnosis of infectious, metabolic or toxic disease, reducing the
percentage of idiopathic or true cases of Reye syndrome. CONCLUSION: Reye
syndrome is a non-specific descriptive term covering a group of heterogeneous
disorders. Moreover, not only the use of acetylsalicylic acid but also of
antiemetics is statistically significant in Reye syndrome cases. Both facts
weaken the validity of the epidemiological surveys suggesting a link with
acetylsalicylic acid.
PMID- 11014462
TI - Current evidence for the use of paediatric antiretroviral therapy--a PENTA
analysis. Paediatric European Network for the Treatment of AIDS Steering
Committee.
AB - The introduction of combination antiretroviral therapy has been associated with a
dramatic clinical improvement in children with human immunodeficiency virus
infection. However, the uptake of antiretroviral therapy has been variable across
Europe. The Paediatric European Network for the Treatment of AIDS Steering
Committee has performed a systematic literature review of paediatric
antiretroviral therapy trials. An analysis of the evidence base for the
commencement and maintenance of antiretroviral therapy was produced. Suggestions
for when to commence antiretroviral therapy, which drugs to start with and how to
monitor and sequence drug regimens are given. CONCLUSION: The aim of these
guidelines is to help in obtaining equity of access to a uniformly high standard
of care for children with human immunodeficiency virus infection in all European
countries.
PMID- 11014463
TI - A preterm baby with Omenn syndrome.
AB - A preterm baby born with scaly skin who later developed recurrent infections and
was subsequently diagnosed to have Omenn syndrome is presented. CONCLUSION: Any
baby with ichthyotic skin and recurrent infections should have immunodeficiency
considered in the differential diagnosis.
PMID- 11014464
TI - Diagnostic potential of neutrophil elastase inhibitor complex in the routine care
of critically ill newborn infants.
AB - It has been suggested that determination of the neutrophil elastase alpha1
proteinase inhibitor complex (E-alpha1PI) improves the diagnosis of bacterial
infection in newborns. We evaluated the use of E-alpha1PI measurements in 143
newborns, consecutively admitted to a tertiary intensive care unit, employing a
new random access assay and a sampling procedure that minimises post-collection
artefacts. The 95% range for noninfected newborns was 20-110 microg/l up to the
5th day of life and 20-85 microg/l thereafter. The sensitivity as to the
diagnosis of culture-proven bloodstream infection was 80% for E-alpha1PI, 86% for
the immature to total neutrophil ratio, 64% for C-reactive protein and 37% for
the total white blood cell count. The corresponding specificity amounted to 97%,
85%, 85% and 86%, respectively. E-alpha1PI increases preceded elevations of C
reactive protein by 18 h. Like C-reactive protein, E-alpha1PI levels did not
distinguish between bloodstream infection and non-bacterial inflammatory
responses. Results of E-alpha1PI became available within 1 h of collection and
usually 2-3 h before manual leucocyte counts. CONCLUSION: Determination of
neutrophil elastase alpha1-proteinase inhibitor levels yields diagnostic
advantages comparable to those of manual differential counts but provide faster
turnaround times.
PMID- 11014465
TI - Risk factors and determinants of neurodevelopmental outcome in cystic
periventricular leucomalacia.
AB - The aim of the study was to determine risk factors for the development of cystic
periventricular leucomalacia (PVL) and to correlate ultrasound findings with
neurodevelopmental outcome. By means of a retrospective case-control study
(matched for gestational age, birth weight, sex, and year of birth) and a cohort
analysis of all preterm infants with cystic PVL documented by ultrasound scans
hospitalised at a local tertiary care centre between 1988 and 1998, 98 preterm
infants with a gestational age ranging from 26 to 35 weeks were diagnosed as
having cystic PVL. The mean day of diagnosis of periventricular echodensities was
3 +/- 2 days (range 1-11 days), and of cystic PVL 21 +/- 8 days (range 2-47
days). Of 79 infants (1988-1997) eligible for neurodevelopmental follow-up (91%),
hemi-, di-, or tetraplegia was diagnosed in 61 (77%), normal mental outcome in 22
(28%), associated visual disorders in 41 (52%) and seizure disorders in 12 (15%)
infants. Significant risk factors associated with the development of cystic PVL
were premature rupture of membranes, chorioamnionitis, and hyperbilirubinaemia
(odds ratios 4.665, 6.026, and 2.460 respectively). Subgroup analysis according
to gestational age (26-28, 29-32, 33-35 weeks) revealed similar results despite
spontaneous labour (26-28 weeks; odds ratio 4.808) and pre-eclampsia (33-35
weeks; odds ratio 3.517). Multiple pregnancy was associated with a twofold
increased risk (odds ratio 2.075). The white matter damage probably accounted for
the significantly higher prevalence of apnoeas (P < 0.001) and neonatal seizures
(P < 0.001). Cysts located bilateral or parieto-occipital were associated with a
higher risk of cerebral palsy (odds ratios 6.933 and 4.327 respectively). Solely
anterior located cysts were associated with normal neurological outcome.
Increasing size of the cysts was associated with increasing risk of cerebral
palsy with a cut-off value of 10 mm (odds ratio 3.300 and above) and all infants
with cysts of more than 20 mm diameter had cerebral palsy. CONCLUSION: The high
prevalence of premature rupture of the membranes and chorioamnionitis further
supports the role of intra-uterine infection in the pathogenesis of
periventricular leucomalacia. The overall prognosis of cystic periventricular
leucomalacia is poor.
PMID- 11014466
TI - Prepubertal diagnosis of X-linked congenital adrenal hypoplasia presenting after
infancy.
AB - X-linked congenital adrenal hypoplasia (CAH) presents classically with adrenal
insufficiency within the first 6 months of life, as the fetal adrenal cortex
progressively involutes. However, there is increasing recognition of delayed
presentation after infancy with the need for accurate molecular diagnosis to
avoid an erroneous diagnosis of other more common causes of adrenal insufficiency
in childhood. We report our genetic studies of a pedigree with two affected boys
presenting with late onset X-linked CAH, diagnosed by the presence of a known
W171X mutation of the DAX-1 gene, in whom the mother was an obligate
heterozygote. Unlike other causes of adrenal insufficiency, the significance of
this diagnosis lies in the important association of hypogonadotropic
hypogonadism, and the provision of accurate genetic counselling. CONCLUSION: This
study demonstrates that genetic analysis for X-linked congenital adrenal
hypoplasia is essential to confirm the diagnosis in prepubertal patients
presenting with adrenal insufficiency after infancy.
PMID- 11014467
TI - Successful treatment of bilateral renal fungal balls with liposomal amphotericin
B and fluconazole in an extremely low birth weight infant.
AB - At the age of 8 weeks, an extremely low birth weight infant (gestational age 26
0/7 weeks, birth weight 740 g) had non-obstructing bilateral renal fungal balls.
Urine cultures had repeatedly grown Candida albicans. Combination therapy with
liposomal amphotericin B intravenously and fluconazole orally was administered
for 6 weeks. Monotherapy with fluconazole was then continued until complete
resolution of the renal fungal balls. CONCLUSION: Combination therapy with
liposomal amphotericin B and fluconazole was successful in eliminating non
obstructing bilateral renal fungal balls and obviated the need for surgical
intervention.
PMID- 11014468
TI - Hospital stay and short-term follow-up of children of drug-abusing mothers born
in an urban community hospital--a retrospective review.
AB - In order to assess the current use of medical and social services of children of
drug-abusing mothers in regard to their short term outcome in a Swiss urban
community hospital, we compared hospital, private paediatricians and home nursing
records of 37 of these children with 37 matched control children from birth to 18
months of age. Children of drug-abusing mothers (CDAM) experienced a longer
neonatal hospital stay than control children with a median (25%-75%) of 26 days
(10.5-52.5 days) versus 5 (5-6) days (P < 0.001), a substantial part of which, 8
days (3.5-26 days) versus 0 days (0-1 day) (P < 0.001) was not motivated by any
specific medical treatment or nursing care. Before discharge, CDAM were referred
to out of hospital nursing and social services for further management, but only
13% were effectively followed. More than 50% were lost to follow-up by their
initial paediatrician after 1 year of life. CONCLUSION: New ways to ensure better
co-ordination between paediatricians and the social services (inside and outside
the hospital) should be developed to shorten the neonatal hospitalisation period
and improve the quality of follow-up.
PMID- 11014469
TI - Necrotising pneumonitis in children.
AB - We retrospectively analysed the clinical features and outcome of children under
17 years of age with necrotising pneumonitis (NP). The radiographs and CT scans
of the chest of children under 17 years of age between July 1995 and March 1999
who had complicating community-acquired pneumonia were reviewed. CT scans were
obtained for persistent fever, respiratory distress and sepsis despite empiric
antibiotic therapy and closed tube drainage. A total of 21 children had the
radiographic features of NP of whom 11 (52%) patients were successfully managed
using antibiotic therapy with or without closed tube drainage. Ten patients
required thoracoscopic decortications and/or lysis of pleural adhesions or
debridement of empyema due to refractory pleural sepsis, failure of pulmonary re
expansion and persistent air-leaks. The most common pathogens identified were
Streptococcus pneumoniae (n = 3), Staphylococcus aureus (n = 2), and Haemophilus
influenzae type b (n = 2). The days of hospital stay, duration of fever and days
of C-reactive protein return to normal were significantly less for the medically
versus the surgically treated children (P < 0.05). CONCLUSION: The clinical
course of necrotising pneumonitis in children following complicated pneumonia is
often prolonged despite adequate antibiotic therapy. Necrotising pneumonitis with
co-existing multiple loculations, pneumothorax/ bronchopleural fistula in the
empyema and extensive pleural peel are poor prognostic factors for medical
therapy. Thoracoscopic removal of loculated empyema, lysis of adhesions and/or
decortication are effective in relieving tachypnoea, chest pain, and controlling
fever and improve the outcome, especially in children with empyema.
PMID- 11014470
TI - Staphylococcus aureus septicaemia in a patient with cystic fibrosis.
AB - Although bacterial colonisation of bronchi may occur from early childhood
onwards, infections extending beyond the lungs are uncommon in patients with
cystic fibrosis. A 12-year-old boy with cystic fibrosis, receiving oral
corticosteroids for 3 weeks because of allergic bronchopulmonary aspergillosis,
experienced pneumonia and septicaemia caused by Staphylococcus aureus. He was
treated with flucloxacillin, ticarcillin-clavulanate, aztreonam, cefazolin and
rifampin according to resistance testing of S. aureus cultured from the blood. On
day 25 the patient finally had recovered. CONCLUSION: Systemic steroid therapy
for allergic bronchopulmonary aspergillosis may favour life-threatening systemic
bacterial infection which is rare in the immunocompetent patient with cystic
fibrosis.
PMID- 11014471
TI - When do children with optic pathway tumours need treatment? An oncological
perspective in 106 patients treated in a single centre.
AB - Progression patterns of optic pathway tumours (OPT) need to be precisely defined
for treatment planning. In patients with neurofibromatosis type 1 (NF1), this
disease is usually indolent and the available literature rarely reports
progression after the age of 6 years. In patients without NF1, the disease course
seems to be less favourable. We reviewed the clinical and radiological files of
106 children referred to our institution for the treatment of a symptomatic OPT
since 1980. NF1 was present in 51 of them. Progression patterns in children with
NF1 differed markedly from those in the other patients. A total of 83 children
had tumour extension beyond the chiasm (Dodge type III). Children with NF1 had
progressive tumours later during follow-up (47% after the age of 6 years), had
more often proptosis and infiltrating tumours but less frequently nystagmus or
increased intracranial pressure. 32 children were not treated at diagnosis
because they had only mild symptoms related to the OPT. In these patients,
progression occurred more often in children without than with NF1 (12/12 versus
12/20 respectively, P = 0.04). A high number of patients needed treatment for
progression or severe symptoms after 6 years of age. Of the patients, 33% needed
treatment for progression or severe symptoms after 6 years of age. CONCLUSION:
Progression patterns of optic pathway tumours in children with neurofibromatosis
type 1 differ markedly from those in other patients. This study emphasises the
need for prolonged follow-up of children with optic pathway tumours, especially
in neurofibromatosis type 1.
PMID- 11014473
TI - Immunodeficiency in alpha-mannosidosis: a matched case-control study on
immunoglobulins, complement factors, receptor density, phagocytosis and
intracellular killing in leucocytes.
AB - Patients with the autosomal recessive lysosomal storage disease alpha
mannosidosis suffer from recurrent infections. To study the mechanisms of this
immunodeficiency, six patients were matched against six healthy controls and
their humoral and cellular immunocompetence investigated. No differences in the
number of circulating leucocytes including B-cells, levels of immunoglobulin main
classes, nor IgG subclasses were observed. However, post-immunisation serum
levels of specific antibodies against poliovirus, diphtheria toxin and tetanus
toxin were significantly reduced. In patients, the density of the complement
binding receptor CD11b and the Fc-receptor CD16 was significantly enhanced on
monocytes and polymorphonuclear neutrophils (PMN) and the number of phagocytosing
PMN was significantly increased in the presence of pooled human serum. This was
not observed in the presence of autologous serum, indicating altered opsonic
properties. Also in normal PMN, phagocytosis was inhibited by a factor in the
serum from the patients. Despite maintained oxidative burst, patient PMN
demonstrated insufficient intracellular bacterial killing. CONCLUSION: Our data
indicate that patients with alpha-mannosidosis have an immunodeficiency at both
the humoral and cellular level.
PMID- 11014472
TI - Therapeutic drug monitoring of once daily gentamicin in serum and saliva of
children.
AB - Gentamicin is widely used in paediatric medicine and therapeutic monitoring is
mandatory due to the narrow margin of safety. Saliva sampling may be of potential
interest, especially in children in whom blood sampling is often difficult.
Experience with once daily intravenous administration of aminoglycosides has
grown in recent years. Gentamicin levels were measured in serum and saliva of 55
children treated with the drug (5 mg/kg per day), administered intravenously in
three different regimens: thrice (n = 19), twice (n = 18), and once daily (n =
18). No correlation was found between serum gentamicin concentrations and saliva
levels when the drug was administered twice or thrice daily, however, there was
good correlation when the drug was administered once daily (r2 = 0.96, P <
0.0001). CONCLUSION: In children with uncomplicated infections treated with once
daily gentamicin, trough concentrations of the drug can be monitored in saliva.
PMID- 11014474
TI - Acute disseminated encephalomyelitis--a diagnosis to consider.
AB - The case history of an 11-year-old boy with post-infectious acute disseminated
encephalomyelitis (ADEM) is presented. ADEM is a diagnosis that is increasingly
being made with the advent of modern radiological techniques. However, the
syndrome cannot be thought of as a discrete clinical entity as it is triggered by
a wide range of factors including infections and vaccinations. Furthermore, other
pathological processes may give the same radiological appearances. The aetiology,
pathophysiology and management of the syndrome are discussed. CONCLUSION: Acute
disseminated encephalomyelitis is a radiological diagnosis that has many
precipitants. Thought must be applied in developing a differential diagnosis to
allow the possibility of targeting treatment at the underlying cause.
PMID- 11014475
TI - An infant with multiple soft tissues masses and abnormal radiological bone
anomalies. Infantile myofibromatosis.
PMID- 11014476
TI - Cerebral vasculitis stabilised by methotrexate.
PMID- 11014477
TI - Interleukin-2 mediated restoration of natural killer cell function in a patient
with Griscelli syndrome.
PMID- 11014478
TI - Colonic perforation in two children with Campylobacter enterocolitis.
PMID- 11014479
TI - Transient neonatal hypothyroidism during breastfeeding after post-natal maternal
topical iodine treatment.
PMID- 11014480
TI - Cross-sectional atomic force microscopy imaging of polycrystalline thin films
AB - Atomic force microscopy (AFM) can be used to image cross-sections of thin-film
samples. So far, however, it has mainly been used to study cross-sections of
epitaxial systems or integrated circuits on crystalline substrates. In this
paper, we show that AFM is a powerful tool to image fractured cross-sections of
polycrystalline thin films deposited on crystalline and non-crystalline
substrates, yielding unique information on the three-dimensional properties of
the cross-sections, with a spatial resolution in the nm range. Original images of
three different heterostructure systems are presented: Si(wafer)/SnO2/CdS/CdTe,
glass/Mo/Cu(In,Ga)Se2,/CdS/ZnO, and glass/SnO2/WO3. We discuss the results by
comparing AFM and scanning electron microscopy (SEM) images, and explain, for the
different materials, why the AFM provides useful additional information.
PMID- 11014481
TI - A new phase consistency criterion and its application in electron crystallography
AB - In this work, we present the principles and potential advantages of a methodology
to assess Fourier components in terms of phase consistency. We define a new phase
consistency criterion among sets of spatially translated images based upon a
novel conception of the spatial shift property of the Fourier transform. The
article shows how this criterion can be used in the alignment stage of the 3D
reconstruction process with a two-fold objective: Assessment of the frequency
components and robustness in the alignment. In that sense, the article shows and
analyzes the results obtained from the application of the new index of quality in
the context of projection image alignment. We have focussed our attention on the
electron crystallography field, by applying such a phase consistency definition
over image reflections. The results that have been obtained show that the new
phase-consistency definition may complement the traditional SNR-based index of
quality (commonly known as IQ) of reflections. As a consequence, the reliability
of the alignment may be improved by discarding those reflections judged as non
reliable according to the phase-consistency criterion.
PMID- 11014482
TI - Selective specimen preparation for TEM observation of the cross-section of
individual carbon nanotube/metal junctions
AB - We present here an efficient method to prepare a transmission electron microscopy
(TEM) specimen for selective observation of the cross-section of individual
nanoscale structures. As a typical example, the cross-sectional TEM observation
of a quasi-one-dimensional material - a nano-electronic component based on an
individual carbon nanotube - is presented.
PMID- 11014483
TI - Alignment of AFM images using an iterative mathematical procedure
AB - An iterative mathematical procedure for the alignment of sequentially recorded
atomic force microscope images (AFM) is presented. The computer program is able
to correct commonly observed drifts in vertical and lateral directions, rotations
around a vertical or lateral axis and differences in scale. This method is
applied on dissolution experiments of uranium dioxide (UO2) surfaces. Images
recorded during in situ experiments, which are shifted probably due to thermal
fluctuations, can be aligned with good accurancy. In a further approach the UO2
surface is marked by electron-beam-induced deposition (EBD or EBID) with
microstructured reference points. The alignment can be distinctly improved using
marked sample surfaces because of the characteristic shape of the markings, which
do not change during the experiment. Furthermore, the markings can be used to
find again a domain on a sample surface. Therefore, AFM images recorded before
and after an ex situ experiment (e.g. treatment in corrosive medium for a longer
period of time) can be aligned with a nanometer spatial resolution.
PMID- 11014484
TI - Light atom derivatives of structure-preserving sugars are unconventional negative
stains.
AB - Although glucose and certain other sugars are known to greatly reduce distortion
and denaturation of proteins during drying, use of this monosaccharide as an
experimental negative stain does not permit imaging of lattice periodicities in
test specimens of thin catalase crystals. However, the potassium and sodium salts
of several forms of monophosphorylated glucose (200 mM), diphosphorylated
glucose, monosulfated glucose, maltose-1-phosphate, and trehalose-6-phosphate,
all dry into a glassy layer and scatter transmitted electrons sufficiently to
show the 86 A major periods in catalase crystals. Glucose-6-phosphate provides
sufficient image contrast at concentrations from 2 mM (=0.067%) to 500 mM (=
16.8%). Underfocusing increases visualization of the periodic lattice, indicating
a large contribution of phase contrast to these images. Upon exposure to the
electron beam, thicker regions of derivatized saccharides or pure glucose develop
bubbling; this redistribution of dried stain largely can be precluded by imaging
with low-dose exposures. Power spectra of images of catalase crystals contained
within 200 mM disodium glucose-6-phosphate show that periodic information can be
recorded to 21 A; some individual features of dipotassium glucose-6-phosphate
distribution within the protein lattice have a measured width of around 5 A. The
experimental results demonstrate that structure-preserving mono- and di
saccharides also serve successfully as negative stains after they are coupled to
light atom scatterers.
PMID- 11014485
TI - Cross-sectional study of the prevalence of feather pecking in laying hens in
alternative systems and its associations with management and disease.
AB - A cross-sectional study of risk factors for feather pecking in layings hens in
alternative systems was carried out in July 1998. A total of 637 questionnaires
were sent out to farmers and producer groups and, after two reminders, the final
response rate was 51.5 per cent. The outcome variable was feather pecking after
point of lay. Over 55 per cent of the farmers reported that feather pecking had
occurred in the last depopulated flock. This outcome was compared with the
management procedures reported by flock managers by using univariate statistics.
Factors associated with feather pecking with a significance < or = 0.05 were then
tested in two logistic regression models. In the first model the following
factors were associated with an increased risk of feather pecking: less than 50
per cent of the flock using the outdoor area on a fine and sunny day, the
occurrence of egg peritonitis and the occurrence of infectious bronchitis. The
direction of the association between feather pecking and these infectious
diseases was unclear, so in the second model only factors which were consistent
throughout the laying period were tested. The following factors were associated
with an increased risk of feather pecking: less than 50 per cent of the flock
using the outdoor area on a fine and sunny day; three or more changes of diet
during lay; the inspection of the flock by one person; an absence of loose litter
at the end of lay; a temperature in the hen house of less than 20 degrees C;
turning the lights up when the flock was inspected; and the use of bell-drinkers.
It is concluded that some of these factors could inhibit foraging and dust
bathing behaviour and others may increase competition or frustration, both of
these changes having been shown experimentally to initiate feather pecking
behaviour.
PMID- 11014486
TI - Fatal adiaspiromycosis in a wild Eurasian otter (Lutra lutra).
AB - Postmortem examination of an immature otter which died in the wild showed that
large areas of the lungs were swollen and firm, with emphysema and haemorrhage in
the remaining areas. Histopathological examination revealed large numbers of
fungal adiaspores and an unusually severe inflammatory response. It was
considered that respiratory impairment was the primary cause of the otter's
death.
PMID- 11014487
TI - Surgical treatment of coenurosis (gid) in sheep.
AB - During the past six years 623 cases of coenurosis (gid) in sheep have been
treated surgically. Cysts were removed successfully from 573 of them (92 per
cent) and 517 (83 per cent) were able to return to their flocks, although 36
showed no clinical improvement In 37 cases, the cyst could not be localised, and
postmortem examinations showed that in nine cases the cyst was in the brainstem,
and in 28 cases it was in the cerebellum. Fifty-six cases deteriorated gradually
after surgery and in these cases more than one cyst was found postmortem.
Thirteen cases died during surgery.
PMID- 11014488
TI - Spring survey of the parasite Heterakis gallinarum in wild-living pheasants in
Britain.
PMID- 11014489
TI - First isolations of leptospires serogroup Ballum serovar arborea in Argentina.
PMID- 11014490
TI - Spontaneous resolution of splenic torsion in a dog.
PMID- 11014491
TI - CSF virus in East Anglia: where from?
PMID- 11014492
TI - Hunting inquiry.
PMID- 11014494
TI - Dermal fibrosis in a rabbit.
PMID- 11014493
TI - Winter transmission of equine nematodes.
PMID- 11014495
TI - Prostaglandin use in sows.
PMID- 11014496
TI - Computer viruses, worms and Internet security.
PMID- 11014497
TI - Sperm binding and penetration of the zona pellucida in vitro but not sperm-egg
fusion in an Australian marsupial, the brushtail possum (Trichosurus vulpecula).
AB - Sperm capacitation and in vitro fertilisation (IVF) have been achieved in most
eutherian mammals and American marsupials under relatively simple culture
conditions. In contrast sperm capacitation in Australian marsupials has not been
achieved in vitro and attempts at IVF have previously been characterised by a
complete lack of sperm-zona pellucida (ZP) binding. Recently, co-culture of sperm
with oviduct epithelial cell monolayers or with oviductal explant conditioned
media has been shown to prolong the viability and motility of brushtail possum
spermatozoa, as well as to induce capacitation-associated changes such as
transformation of sperm to the T-shape orientation. In this study we report that
these in vitro produced T-shaped sperm, and in vivo derived T-shaped sperm
flushed from the oviduct of artificially inseminated possums as a control, are
able to bind to and penetrate the ZP of approximately 25% of eggs recovered from
PMSG/LH-superovulated possums in vitro. Development of ZP receptivity and
penetrability towards sperm was also identified as a major factor affecting the
outcome of IVF. Neither in vivo nor in vitro derived T-shaped sperm were able to
bind to or penetrate the ZP if eggs were obtained from animals that were treated
with pLH less than 76 h after PMSG. Thus this study provides preliminary evidence
for the necessity of sperm-oviduct epithelial cell interactions for capacitation
in Australian species and lends further support to the suggestion that the T
shape head orientation is indicative of sperm capacitation. Despite the
occurrence of sperm-ZP binding and penetration, sperm-egg membrane fusion and egg
activation were not observed. Although the factor(s) responsible for the lack of
sperm-egg membrane fusion in the possum have not been identified it is possible
that egg capacity for membrane fusion develops independently of zona receptivity
and is defective in these eggs, or alternatively that membrane fusion requires
strictly defined ionic conditions which are not provided by the IVF media used in
this study.
PMID- 11014498
TI - Sperm decondensation during fertilisation in the mouse: presence of DNase I
hypersensitive sites in situ and a putative role for topoisomerase II.
AB - In this study our aim was to characterise the presence and the role of DNA
alterations during sperm decondensation in the mouse. To visualise the changes
during decondensation we investigated for the presence of DNase I hypersensitive
sites in situ and for a putative role for topoisomerase II by examining the
effect of teniposide, a topoisomerase II inhibitor, during fertilisation. In situ
nick translation without the previous addition of DNase I failed to reveal the
presence of endogenous nicks in decondensing sperm and pronuclei whereas
preincubation of fixed oocytes with DNase I indicated that decondensing sperm
were sensitive to this enzyme. Addition of 100 microM teniposide did not
completely inhibit pronuclei formation but its addition to the fertilisation
medium did lead to the presence of endogenous DNA nicks in decondensing sperm.
These observations suggest that DNase I hypersensitivity during sperm
decondensation is related to the dramatic conformational changes that the
chromatin undergoes during the decondensation process, in which topoisomerase II
may be implicated.
PMID- 11014499
TI - Effective activation method with A23187 and puromycin to produce haploid
parthenogenones from freshly ovulated mouse oocytes.
AB - Freshly ovulated mouse oocytes exposed to 5 mM calcium ionophore A23187 for 5 min
and controls (not exposed) were cultured in TYH medium with 10 microg/ml
puromycin (the puromycin group) or 2 mM 6-dimethylaminopurine (DMAP; the DMAP
group) for 4 h. Among the controls, few oocytes were activated even if they were
treated with DMAP or puromycin. In the oocytes exposed to A23187, in contrast,
the activation rate, i.e. the rate of oocytes showing at least one pronucleus
(PN) after the treatment, was 46.2% (48/104) in the DMAP group and 90.0%
(118/131) in the puromycin group. Activation rate in the puromycin group was
significantly higher than in the DMAP and control groups (p < 0.0001,
respectively). Furthermore, 82.4% (108/131) of the activated oocytes in the
puromycin group showed one PN with extrusion of the second polar body (PB). In
the puromycin group, the DNA content of the PN of parthenogenones with 1PN2PB was
half that of a set of metaphase II chromosomes. Chromosomal analysis was possible
in 14 parthenogenones with 1PN2PB in the puromycin group. The parthenogenones
possessed a normal set (n = 20) of haploid chromosomes. The combination of A23187
and puromycin proved to be an effective method of producing haploid
parthenogenones.
PMID- 11014500
TI - Quantification of mtDNA in single oocytes, polar bodies and subcellular
components by real-time rapid cycle fluorescence monitored PCR.
AB - Oocytes, in general, are greatly enriched in mitochondria to support higher rates
of macromolecular synthesis and critical physiological processes characteristic
of early development. An inability of these organelles to amplify and/or to
accumulate ATP has been linked to developmental abnormality or arrest. The number
of mitochondrial genomes present in mature mouse and human metaphase II oocytes
was estimated by fluorescent rapid cycle DNA amplification, which is a highly
sensitive technique ideally suited to quantitative mitochondrial DNA (mtDNA)
analysis in individual cells. A considerable degree of variability was observed
between individual samples. An overall average of 1.59 x 10(5) and 3.14 x 10(5)
mtDNA molecules were detected per mouse and human oocyte, respectively.
Furthermore, the mtDNA copy number was examined in polar bodies and contrasted
with the concentration in their corresponding oocytes. In addition, the density
of mtDNA in a cytoplasmic sample was estimated in an attempt to determine the
approximate number of mitochondria transferred during clinical cytoplasmic
donation procedures as well as to develop a clinical tool for the assessment and
selection of oocytes during in vitro fertilisation procedures. However, no
correlation was identified between the mtDNA concentration in either polar bodies
or cytoplasmic samples and their corresponding oocyte.
PMID- 11014501
TI - Lack of cell cycle checkpoints in human cleavage stage embryos revealed by a
clonal pattern of chromosomal mosaicism analysed by sequential multicolour FISH.
AB - Multicolour fluorescence in situ hybridisation (FISH) analysis of interphase
nuclei in cleavage stage human embryos has highlighted a high incidence of
postzygotic chromosomal mosaicism, including both aneuploid and ploidy mosaicism.
Indeed, some embryos appear to have a chaotic chromosomal complement in a
majority of nuclei, suggesting that cell cycle checkpoints may not operate in
early cleavage. Most of these studies, however, have only analysed a limited
number of chromosomes (3-5), making it difficult to distinguish FISH artefacts
from true aneuploidy. We now report analysis of 11 chromosomes in five sequential
hybridisations with standard combinations of two or three probes and minimal loss
of hybridisation efficiency. Analysis of a series of arrested human embryos
revealed a generally consistent pattern of hybridisation on which was
superimposed frequent deletion of one or both chromosomes of a specific pair in
two or more nuclei indicating a clonal origin and continued cleavage following
chromosome loss. With a binucleate cell in a predominantly triploid XXX embryo,
the two nuclei remained attached during preparation and the chaotic
diploid/triphoid status of every chromosome analysed was the same for each
nucleus. Furthermore, in each hybridisation the signals were distributed as a
mirror-image about the plane of attachment, indicating premature decondensation
during anaphase consistent with a lack of checkpoint control.
PMID- 11014502
TI - Effects of sex steroid hormones and their antagonists on mast cell number in the
testis of the frog, Rana esculenta.
AB - This study confirms our previous data on the effects of sex hormones on mast cell
number (MCN) in the testis of frog Rana esculenta. After 15 days of treatment
with oestradiol (E2) MCN strongly increases, while testosterone has no effect.
After 30 days only a small increase in MCN is observed. These differences could
be due to the non-physiological effect of E2 over a prolonged period. We also
confirmed a massive increase in MCN after 15 or 30 days of treatment with
cyproterone acetate (CPA). This increase in MCN is also observed after
administration of CPA with tamoxifen. Ultrastructural analysis of testis shows
empty spaces with degenerating Leydig cells in the interstitial compartment and
numerous germinal cells completely degenerated, probably apoptotic, in the
adjacent germinal compartment. The same effects were observed in testes after
treatment with only CPA. Chronic E2 treatment provokes an increase in MCN on day
2. From day 4 to 12 of the treatment, MCN decreases dramatically and many
germinal tubules appear strongly disorganised. In conclusion, the present results
confirm that E2 treatment induces changes in MCN and chronic E2 treatment
modifies the morphology of the frog testes. In addition, blocking androgen
receptors with CPA, alone or in combination with tamoxifen, causes a significant
increase in MCN, confirming the involvement of androgens in mast cell
proliferation and/or differentiation.
PMID- 11014503
TI - The effects of embryo stage and cell number on the composition of mouse
aggregation chimaeras.
AB - Studies with intact preimplantation mouse embryos and some types of chimaeric
aggregates have shown that the most advanced cells are preferentially allocated
to the inner cell mass (ICM) rather than the trophectoderm. Thus, differences
between 4-cell and 8-cell stage embryos could contribute to the tendency for
tetraploid cells to colonise the trophectoderm more readily than the ICM in 4
cell tetraploid<-->8 cell diploid chimaeras. The aim of the present study was to
test whether 4-cell stage embryos in 4-cell diploid<-->8-cell diploid aggregates
contributed equally to all lineages present in the E12.5 conceptus. These
chimaeras were compared with those produced from standard aggregates of two whole
8-cell embryos and aggregates of half an 8-cell embryo with a whole 8-cell
embryo. As expected, the overall contribution of 4-cell embryos was lower than
that of 8-cell embryos and similar to that of half 8-cell stage embryos. In the 4
cell<-->8-cell chimaeras the 4-cell stage embryos did not contribute more to the
trophectoderm than the ICM derivatives. Thus, differences between 4-cell and 8
cell embryos cannot explain the restricted tissue distribution of tetraploid
cells previously reported for 4-cell tetraploid<-->8-cell diploid chimaeras. It
is suggested that cells from the more advanced embryo are more likely to
contribute to the ICM but, for technical reasons, are prevented from doing so in
simple aggregates of equal numbers of whole 4-cell and whole 8-cell stage
embryos.
PMID- 11014504
TI - Chlortetracycline staining patterns of frozen-thawed bull spermatozoa treated
with beta-cyclodextrins, dibutyryl cAMP and progesterone.
AB - Efforts to achieve complete chemical definition of media used for in vitro
capacitation of bovine spermatozoa including removal of heparin purified from
porcine intestinal mucosa are presented. Fluorescent staining with
chlortetracycline (CTC), known to reflect changes coincident with sperm
capacitation in certain species, was studied following treatments of frozen
thawed bull spermatozoa with beta-cyclodextrins, dibutyryl cAMP (dbcAMP) and
progesterone in comparison with heparin. The CTC staining patterns (F, B and AR)
were confirmed to correlate with known conditions that effectively prepare
cryopreserved bull spermatozoa for fertilisation in vitro. In the absence of
glucose, the routinely employed heparin-containing capacitating medium caused an
increase in spermatozoa displaying the AR pattern. Both progesterone (100 microM)
and dbcAMP (0.01-0.1 mM) were able to increase the proportion of B pattern
stained sperm cells more than after exposure to control (mDM) conditions without
a significant reduction in motility. Exposure to either dbcAMP or beta
cyclodextrins was accompanied by an increase in proportions of spermatozoa
displaying the AR pattern over those seen in controls. Exposure to beta
cyclodextrins did not increase the proportion of B pattern stained spermatozoa.
Comparison of spermatozoa from two bulls revealed differential responses of
spermatozoa from different males to treatments with heparin and progesterone. In
vitro fertilisation results demonstrated that previously cryopreserved bull
spermatozoa could be capacitated in chemically defined conditions devoid of
heparin or other biological components.
PMID- 11014505
TI - Enzymes responsible for the bactericidal effect in extracts of vitelline and
fertilisation envelopes of rainbow trout eggs.
AB - Extracts from both the vitelline envelope (VE) and fertilisation envelopes (FE)
of rainbow trout eggs have the ability to exert a bactericidal effect on Gram
positive and -negative bacteria. The effect may be due to the presence of
phospholipase D (PLD), lysozyme, proteinase and DNases, as the extracts contain
these enzyme activities. The intensity of chorionic PLD and lysozyme activities
in the VE extract was maintained in the FE without any alteration in activity
even after transformation in the course of the cortical reaction, as components
of a fundamental architecture of the envelope. Both extracts also contain
different types of proteinase activities. Treatment with VE or FE extract
seriously damaged the outer membrane of Gram-negative bacteria and the plasma
membrane of Gram-positive and -negative bacteria at the ultrastructural level.
Chorionic DNases probably degrade DNA of bacterial cells killed by virtue of the
action of PLD and/or lysozyme and contribute to the transmigration of nucleosides
and/or nucleotides produced by degrading bacterial DNA after degradation of
bacterial components by the actions of the chorionic PLD, lysozyme and
proteinase. These results suggest that the bactericidal process manifested by the
VE or FE extract may start with the action of PLD and/or lysozyme against
bacteria and be completed by subsequent degradation of constitutive proteins and
DNA by the action of proteinases and DNases, respectively. Thus the VE and FE are
able to protect the egg itself and the embryo, respectively, from bacterial
infection in the internal or external environments.
PMID- 11014506
TI - Fertilisability of ovine, bovine or minke whale (Balaenoptera acutorostrata)
spermatozoa intracytoplasmically injected into bovine oocytes.
AB - This study was conducted to investigate the possibility of using bovine oocytes
for a heterologous fertility test by intracytoplasmic sperm injection (ICSI) and
to compare the pronuclear formation of ram, bull and minke whale spermatozoa
after injection into bovine oocytes. Bovine oocytes were cultured in vitro for 24
h and those with a polar body were selected for ICSI. Frozen-thawed semen from
the three species were treated with 5 mM dithiothreitol for 1 h and spermatozoa
were killed by storing them in a -20 degrees C refrigerator before use. ICSI was
performed using a Piezo system. Three experiments were designed. In experiment 1,
a higher (p < 0.05) male pronuclear formation rate was found in the oocytes
injected with ram (52.6%) or bull (53.4%) spermatozoa than with minke whale
spermatozoa (39.1%). In experiment 2, sperm head decondensation was detected at 2
h after ICSI in the oocytes injected with a spermatozoon of each species. Male
pronuclei were first observed at 4 h in the oocytes injected with ram or bull
spermatozoa and at 6 h in oocytes injected with minke whale spermatozoa. The mean
diameters of male pronuclei derived from both whale and bull spermatozoa were
larger than those from ram spermatozoa (30.4 microm and 28.3 microm vs 22.4
microm, p < 0.005). The mean diameter of female pronuclei in the oocytes injected
with whale spermatozoa was also larger than with ram spermatozoa (29.3 microm vs
24.7 microm, p < 0.05). The development of male and female pronuclei was
synchronous. In experiment 3, ethanol-activated oocytes injected with a
spermatozoon from any of the three species achieved significantly higher (p <
0.05-0.001) cleavage rates than control oocytes. Blastocyst formation was only
observed when bull spermatozoa were used. The results of this study indicate that
dead foreign spermatozoa can participate in fertilisation activities in bovine
oocytes after ICSI.
PMID- 11014507
TI - The effect of growth hormone on rat pre-antral follicles in vitro.
AB - The aim of the present study was to investigate whether growth hormone (GH) has
any effect on the development of cultured rat pre-antral follicles. Pre-antral
follicles with a diameter between 120 microm and 160 microm were mechanically
isolated from 10-day-old rat ovaries and cultured in groups for 6 days in serum
free medium without GH or with GH supplemented at concentrations of 1, 10 and 100
ng/ml, respectively. DNA content of the follicles before and after culture was
measured to determine whether possible growth is due to proliferation of
follicular cells. To investigate the quality of follicles cultured under
different conditions, the ultrastructure of the cultured follicles was studied
with transmission electron microscopy. Furthermore, reverse transcriptase
polymerase chain reaction (RT-PCR) was used to assess the expression of growth
hormone receptor (GHR) in pre-antral follicles. GH, regardless of the
concentration, stimulated the growth of pre-antral follicles. However, follicles
cultured in medium supplemented with high-dose GH (100 ng/ml) showed a
significantly lower survival rate compared with the other groups. Follicles
cultured in GH-containing medium showed a better ultrastructure in comparison
with those cultured in medium without GH. Remarkably, scattered cortical granules
were observed in oocytes of follicles cultured in the presence of GH. With RT
PCR, the presence of the mRNA of GHR was demonstrated in pre-antral follicles. It
can be concluded that GH promotes rat pre-antral follicle development in vitro
and better supports the morphology of cultured pre-antral follicles. The gene
expression of GHR suggests that the action of GH could be mediated by its
receptors present in pre-antral follicles.
PMID- 11014508
TI - Decision-making for national programs of community fluoride use.
AB - Every community, region or country with a high or rising prevalence of dental
caries should implement a caries-preventive program that automatically brings the
benefits of systemic and topically applied fluoride to the entire population. The
fluoridation of community water supplies or salt fulfills the requirements of
providing safe, effective protection from dental caries at reasonable cost. The
use of dietary fluoride supplements or fluoridated milk does not meet the
requirements of a comprehensive national or community program because compliance
is poor or only selected age groups are targeted. Water fluoridation is ideal for
countries, regions or communities with many central water supplies or where salt
production or distribution is not centralized or easy to control. Water
fluoridation also has advantages where many areas exist with natural water
fluoride concentrations at optimal or greater than optimal concentrations. Salt
fluoridation is ideal for countries or regions with few, potable central water
supplies in which salt production and distribution are centralized and easily
controlled. Concentrations of fluoride for water fluoridation range from 0.5 to
1.2 parts per million (ppm) parts of water depending on climate and dietary
practices. The concentration for fluoridation of salt is approximately 200 to 250
mg fluoride per kg of salt, also depending on dietary practices. Properly
fluoridated salt should produce levels of urinary fluoride excretion similar to
those found in communities with fluoridated water. Benefits of the two methods
are similar. Salt fluoridation may be done more cheaply.
PMID- 11014509
TI - Reliability and validity of the Dental Indifference Scale in a population of 18
year-olds in Norway.
AB - OBJECTIVES: The aims of this study were to estimate the reliability and validity
of the Dental Indifference Scale (DIS) (Nuttall, 1996) in a population of 18-yr
olds in Norway. METHODS: The DIS-scale was mailed to a sample of 1119 18-yr-olds
in two Norwegian counties. Nearly 87% completed the questionnaire and consented
to the collection of data from their dental records. Ten percent of the sample,
drawn at random, was asked to complete the questionnaire a second time, after a
time delay of 15 weeks (response rate 83%). The reliability estimation of the sum
scores of DIS was based on Pearson's correlation between test-retest scores and
internal consistency (Cronbach's alpha). The frequency of missed appointments
from age 12, recorded in the dental treatment records, was used as the validating
criterion. The validity was analyzed by Pearson's correlation, and step-wise
multiple regression. RESULTS: The correlation coefficient (Pearson) for the test
retest comparison was 0.43. The correlation coefficient between the DIS-scores
and the frequencies of missed dental appointments was 0.24. The Cronbach's Alpha
coefficient for the eight DIS-questions was 0.35 (n=868). Only two of the eight
DIS-questions entered the stepwise regression model and explained 15% of the
variance of the frequency of missed appointments. CONCLUSIONS: The Dental
Indifference Scale (DIS) was found to have a low reliability and validity in this
study population, and it is recommended that it should not be used without
further investigation. It may be necessary to design an alternative instrument if
further work into the hypothesized trait of dental indifference is to be
undertaken.
PMID- 11014510
TI - Oral hygiene knowledge of high-risk Grade One children: an evaluation of two
methods of dental health education.
AB - The effectiveness of two methods of dental health education (DHE) for improving
oral hygiene knowledge among high-risk Grade One students was evaluated. Fifty
elementary schools in the former City of North York, Canada were assigned to one
of two groups. In one group, students received a classroom-based DHE lesson which
was reinforced by two small-group sessions (n=243). In the other group, students
received only a single classroom-based DHE lesson (n=206). After DHE
interventions, students in both groups displayed improved knowledge for most oral
hygiene questions (e.g., when should you throw your toothbrush away?). However,
for several questions, a significantly higher proportion of "classroom plus small
group sessions" students displayed improved knowledge compared to students
receiving only a classroom lesson. These items included: awareness that cavity
prevention and removal of germs are two purposes of oral hygiene; and knowledge
that teeth help people to eat and talk. Results suggest a classroom-based lesson
combined with small-group sessions is a more effective method of improving oral
hygiene knowledge among high-risk Grade One students compared to a single
classroom-based lesson.
PMID- 11014512
TI - Variation in caries and treatment experience in 35-44-year-old Lithuanians.
AB - Data summarising caries levels differ between countries and often conceal large
variations. These differences may reflect variations at individual, group, social
and other levels. Caries and treatment experience differences are found to be
significantly related to a variety of clinical and non-clinical factors.
Variation in caries within Lithuanian children has been reported and related to
background-, behavior-, dental care- and other factors. Variation in general or
related to any factors in adult Lithuanian population has not been studied. The
aim of the present study was to estimate variation in caries and treatment
experience and relate them to biological-, psychosocial-, health-related,
behavioral- and dental care related aspects. The existing knowledge from other
oral health studies was used to select the factors found of importance in
relation to variations in caries scores. The study consisted of clinical and self
reported data collected from a stratified random sample of 382 individuals
(attendance rate 50%). Two statistical approaches, a bivariate and a
multivariate, were applied. The two dependent variables DMFT and DS were tested
with a set of independent variables. The bivariate analysis revealed significant
associations for approximately one half of all variables studied. For
multivariate testing, a backward linear multiple regression was used. Forty-one
percent of the variation in DS was explained and 48% in DMFT scores. Differences
in scores were related to various factors in the two analyses. The strength and
significance of a few relationships differed in both of the analyses. The
multivariate testing revealed some strong and significant associations with
independent variables which were found to be weak and non-significant (P>0.05)
when tested bivariately and vice versa. Less than half of the variation could be
explained in dental caries scores in 35-44-year-olds and not only dental care
related factors were important. In both of the analyses, the varying degrees of
strength (significance levels) give rise to a hypothesis that this incomplete
explanation of the variation can be due to interrelated effects of different
estimates.
PMID- 11014511
TI - The fractional urinary fluoride excretion in young children under stable fluoride
intake conditions.
AB - The purpose of this study was to determine the fraction of the total daily
fluoride intake that is excreted through the urine (FUEF) of children aged 3-5
years under usual intake conditions. Participating children were residents of an
area with a fluoride (F) concentration of 0.5-0.6 mg/L in their drinking water.
Assessments were made on two successive 24-h periods on 20 children, measuring
the total amount of fluoride ingested through liquid and food consumption, and
from ingestion of fluoridated toothpaste (500 microg F/g), together with the
determination of the amount of fluoride excreted through urine. Fluoride
retention was also estimated assuming a constant average F fraction of 10%
excreted through faeces. It was found that the average proportion of liquids,
solid foods, and toothpaste to the daily fluoride intake (1.02-mg F/day on
average) were 40.8, 34.6, and 24.5%, respectively. The average FUEF value was
35.5% (95% C.I.=31.7-39.3%), and the estimated fractional F retention was 54.5%.
The present data suggest a slight relationship between FUEF values and the
inverse of the daily fluoride dose (1/dose) (r=0.513; P=0.021). When the present
results are combined with those from previous studies on F-retention and urinary
excretion, the correlation between both FUEF and fractional retention and 1/dose
are very strong and highly significant (r=0.98, P<0.0001, and r=-0.986, P<0.0001,
respectively). A possible mechanism is suggested in order to explain this latter
finding. The potential usefulness of the current FUEF value for the estimation of
daily F intake (or dose) from urinary F excretion data is also discussed.
PMID- 11014513
TI - A longitudinal study of young Finnish adults' use of subsidized, private sector
dental care, 1986-1997.
AB - OBJECTIVES: Finns born after 1956 are now entitled to subsidized private sector
dental care, or such persons could be enrolled in the Public Dental Service.
Until 1986, eligibility was more restrictive. The purpose of this study was to
investigate the use and costs of private dental care and effects of regularity of
care on costs and treatment received among young Finnish adults during 1986-1997.
METHODS: All 1986, 1990 and 1994 recipients of reimbursement for dental care from
the Social Insurance Institution were included in the study. Five separate age
cohorts were compared. Using their civil registration numbers, individuals were
tracked from their first contact with a private dentist in one of the years 1986,
1990 or 1994 until the year 1997. RESULTS: While the total number of young adults
who had received reimbursement for private dental care increased from about 53000
(1986) to 200000 (1994) due to extended eligibility, the number of users in the
youngest group decreased from 53000 to 23000. Attending infrequently (1-2 times
during the study period) was most common among the youngest adults and frequent
attendance (annually) was most common among older adults. The annual mean cost
was slightly lower among the frequent attenders in almost every cohort. Variation
in the mean number of annual visits was directly correlated with costs. Frequent
attenders most often received diagnostic and preventive measures while
restorations and surgery were most common for the infrequent attenders.
CONCLUSIONS: A substantial decline in the demand for private services among the
19-25-year-olds and stable demand among 26-34-year-olds was detected, indicating
falling treatment needs or a preference for the Public Dental Service. All groups
had a stable mean number of visits per year and almost constant costs. The mean
number of dental visits per year remained steady in all cohorts indicating rigid
treatment patterns.
PMID- 11014514
TI - Salivary alterations in type 2 (non-insulin-dependent) diabetes mellitus and
hypertension.
AB - OBJECTIVES: The aim of this study was to determine whether saliva output and
composition are altered in type 2 diabetes mellitus by comparison with a healthy,
non-medicated control group, and also a group of hypertensives. METHODS: From a
community-dwelling cohort of Mexican American and European American subjects
enrolled in the OH:SALSA oral aging study, we identified 233 subjects with type 2
diabetes mellitus, 227 with hypertension, and 240 healthy control subjects. We
collected unstimulated whole (UW) and submandibular/ sublingual (US) saliva, as
well as stimulated parotid (SP) and submandibular/ sublingual (SS) saliva. Flow
rates were determined, yeast carriage was assayed in UW saliva, and SP and SS
saliva samples were analyzed for protein composition. ELISA was used to determine
concentrations of an array of specific protein components, with both
antimicrobial and other activities. RESULTS: Both diabetic and hypertensive
subjects had reduced output of both stimulated and unstimulated
submandibular/sublingual saliva. 30% of the diabetic subjects had high oral yeast
counts (> or =1000 cfu/mL) compared with 17% of the healthy subjects and 20% of
the hypertensives. Significant increases in the concentrations of a number of the
protein components were found in the diabetic subjects, specifically, SP
lactoferrin, myeloperoxidase (MPO), and salivary peroxidase (SPO), as well as SS
total protein, albumin, lactoferrin and secretory IgA. CONCLUSIONS: The pattern
of decreased flow rates and increased protein concentrations were similar, but
consistently greater in diabetics than hypertensives, suggesting that disease
specific mechanisms may be responsible. Diabetics may be more prone to oral
dryness and infections than non-diabetics.
PMID- 11014515
TI - Decline of caries prevalence after the cessation of water fluoridation in the
former East Germany.
AB - In contrast to the anticipated increase in dental caries following the cessation
of water fluoridation in the cities Chemnitz (formerly Karl-Marx-Stadt) and
Plauen, a significant fall in caries prevalence was observed. This trend
corresponded to the national caries decline and appeared to be a new population
wide phenomenon. Additional surveys (N=1017) carried out in the formerly
fluoridated towns of Spremberg (N=9042) and Zittau (N=6232) were carried out in
order to support this unexpected epidemiological finding. Pupils from these
towns, aged 8/9-, 12/13- and 15/16-years, have been examined repeatedly over the
last 20 years using standardised caries-methodological procedures. While the data
provided additional support for the established fact of a caries reduction
brought about by the fluoridation of drinking water (48% on average), it has also
provided further support for the contention that caries prevalence may continue
to fall after the reduction of fluoride concentration in the water supply from
about 1 ppm to below 0.2 ppm F. Caries levels for the 12-year-olds of both towns
significantly decreased during the years 1993-96, following the cessation of
water fluoridation. In Spremberg, DMFT fell from 2.36 to 1.45 (38.5%) and in
Zittau from 2.47 to 1.96 (20.6%). These findings have therefore supported the
previously observed change in the caries trend of Chemnitz and Plauen. The mean
of 1.81 DMFT for the 12-year-olds, computed from data of the four towns, is the
lowest observed in East Germany during the past 40 years. The causes for the
changed caries trend were seen on the one hand in improvements in attitudes
towards oral health behaviour and, on the other hand, to the broader availability
and application of preventive measures (F-salt, F-toothpastes, fissure sealants
etc.). There is, however, still no definitive explanation for the current pattern
and further analysis of future caries trends in the formerly fluoridated towns
would therefore seem to be necessary.
PMID- 11014516
TI - Oral mucosal lesions in a representative cross-sectional study of aging Germans.
AB - OBJECTIVES: To determine prevalence of oral mucosal lesions in a cross-sectional
study among aging Germans. METHODS: Three specially trained dental teams examined
adults (35-44 yrs, Group 1) and senior individuals (65-74 yrs, Group 2) in 90
sample points of which 60 were located in the former West and 30 in the former
East part of Germany. The spectrum comprised 28 different oral lesions with
subforms. RESULTS: 655 individuals in Group 1 (35-44 yrs) and 1367 individuals in
Group 2 (65-74 yrs) were studied. 33.8% (Group 1) and 33.9% (Group 2) were
without any pathology of the oral mucosa. Several lesions were not recorded in
both Groups like oral hairy leukoplakia and gingival hyperplasia (Group 1 and
two) and xerostomia (Group 1). In Group 1 history for labial herpetic lesions
(31.7%), Fordyce granules (26.6%), history for recurrent aphthous ulceration
(18.3%) and lip and/or cheek biting (10.1%) were recorded. In Group 2 Fordyce
granules (23.7%), history of labial herpes (20.0%), plicated tongue (19.0%) and
denture stomatitis (18.3%) were those lesions most frequently recorded.
Leukoplakia was seen in 1.8% (West) and 0.9% (East) respectively; men were more
often affected than women (2.3% versus 0.0% P<0.05, Group 1; 2.3% versus 0.9%,
Group 2. There was association between the prevalence of leukoplakia and a lower
(3.3%) or higher educational level (0.5%). Denture associated lesions were seen
in 18.3% (Group 2) compared to 2.5% (Group 1) (P<0.001). Other age-related
lesions were lip and/or cheek biting being more prevalent in Group 1 10.1% versus
1.9% (P<0.001), plicated tongue 19.0% in Group 2 versus 3.8% in Group 1
(P<0.001). CONCLUSIONS: The present study has shown prevalence to be comparable
to other relevant Western European studies. Since the spectrum of oral mucosal
lesions changes with age and increases with general morbidity, routine
examinations of oral cavities of the aging are mandatory particularly to detect
early precancerous and other mucosal lesions.
PMID- 11014517
TI - Multitoxin biosensor-mass spectrometry analysis: a new approach for rapid, real
time, sensitive analysis of staphylococcal toxins in food.
AB - Biomolecular interaction analysis mass spectrometry (BIA-MS) was applied to
detection of bacterial toxins in food samples. This two-step approach utilizes
surface plasmon resonance (SPR) to detect the binding of the toxin(s) to
antibodies immobilized on a surface of a sensor chip. SPR detection is then
followed by identification of the bound toxin(s) by matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry. Staphylococcal
enterotoxin B (SEB) was readily detected in milk and mushroom samples at levels
of 1 ng/ml. In addition, non-specific binding of food components to the
immobilized antibody and to the sensor chip surface was detected. To evaluate the
applicability of BIA-MS in the analysis of materials containing multiple toxic
components, sample containing both SEB and toxic-shock syndrome toxin-1 was
analyzed. Both toxins were successfully and simultaneously detected through the
utilization of multiaffinity sensor chip surfaces.
PMID- 11014518
TI - Microbial species associated with different sections of broccoli harvested from
three regions in Australia.
AB - The microbial populations associated with the different sections of broccoli
harvested from three locations in Australia were studied during storage at 5, 15
and 20 degrees C. Bacterial and yeast populations associated with the outer
florets and cut surfaces of the stem were generally 10-fold or more higher than
those associated with inner florets or non-cut stems, respectively. The
predominating bacterial species varied with the origin of the broccoli.
Pseudomonas fluorescens, Ps. corrugata and Ps. viridiflava predominated at
populations of 10(5)-10(7) cfu/g on broccoli harvested from Victoria, Ps.
fluorescens, Ps. mendocina and Ps. fragii and Arthrobacter spp. (10(-3) 10(6)
cfu/g) were prevalent on broccoli harvested from Queensland. Broccoli harvested
from New South Wales exhibited a predominance of Ps. fluorescens, Arthrobacter
spp. and Enterobacteragglomerans (10(3)-10(5) cfu/g). Most species grew on
broccoli during storage. Similar species were found at the different sections of
broccoli, although, for some species there was evidence of strain variation at
the different locations and for different temperature of storage.
PMID- 11014519
TI - Action of lysozyme and nisin mixtures against lactic acid bacteria.
AB - Lysozyme was formulated together with nisin for usage against food spoilage
lactobacilli. The mixtures demonstrated improved minimal inhibitory
concentrations (MIC), compared to the parent compounds, for many of the bacteria
and media tested, including high salt media in which lysozyme lost virtually all
of its activity. Synergy was also observed through measurement of the kinetics of
bacterial killing of L. curvatus 845, in which strain synergy had been observed
in MIC assays. The combination of lysozyme and nisin caused more severe cell
damage as viewed by scanning electron microscopy, and a consequent change in
optical density at 600 nm, compared to the parent compounds, effects that were
presumed to reflect the action of lysozyme. In addition, the combination caused
more rapid permeabilization (depolarization) of the cytoplasmic membranes of
Staphylococcus aureus, an effect that reflected the mechanism of action of nisin.
Thus, nisin and lysozyme appear to demonstrate synergy against gram-positive
bacteria because they reinforce each others mechanisms of bacterial killing.
PMID- 11014520
TI - Interactions of high hydrostatic pressure, pressurization temperature and pH on
death and injury of pressure-resistant and pressure-sensitive strains of
foodborne pathogens.
AB - The objective of this study is to determine the interactions between high
hydrostatic pressure, pressurization temperature, time and pH during
pressurization on death and injury of pressure-resistant and pressure-sensitive
strains of four foodborne pathogens: Staphylococcus aureus 485 and 765, Listeria
,monocytogenes CA and OH2, Escherichia coli O157:H7 933 and 931, Salmonella
enteritidis FDA and Salmonella typhimurium E21274. Among these strains S. aureus
485, L. monocytogenes CA, E. coli O157:H7 933 and S. enteritidis FDA were
reported to be more pressure-resistant than the respective strain of the same
species (Alpas et al., 1999). In general, viability loss of all pathogens was
enhanced significantly as the level of pressure and temperature were increased (P
< 0.05). All the strains except S. aureus 485 demonstrated more than 8 log cycle
reduction when pressurized at 345 MPa at 50 degrees C for 5 min. This strain
seemed to be the most pressure-resistant strain within the conditions of the
study. Pressurization in the presence of either citric or lactic acid increased
the viability loss by an additional 1.2-3.9 log cycles at pH 4.5 for both acids
at 345 MPa. This study has indicated that high hydrostatic pressure applied in
conjunction with mild heat and acidity can be an effective method for
inactivating pressure-resistant and pressure-sensitive strains of four foodborne
pathogens in organic acid solutions. This combination treatment indicates
possible pressure pasteurization applications to liquid foods that have low pH.
reserved.
PMID- 11014521
TI - Phenotypic and genetic diversity of Saccharomyces contaminants isolated from
lager breweries and their phylogenetic relationship with brewing yeasts.
AB - A taxonomic study was carried out for isolates of Saccharomyces spp. identified
as contaminants ("wild yeast") in 24 different lager breweries. With reference to
the current taxonomy all isolates were found to belong to the Saccharomyces sensu
stricto complex and 58% of the isolates were further identified as S. cerevisiae,
26% as S. pastorianus and 3% as S. bayanus. The remaining isolates (13%) could
not be identified to the species level based on their phenotypic characteristics.
However, some of these isolates were identified as S. cerevisiae by HaeIII
restriction digest of PCR-amplified intergenic transcribed spacer (ITS) regions.
Chromosome length polymorphism (CLP) was evident among the Saccharomyces brewing
contaminants with chromosome profiles typical of Saccharomyces sensu stricto.
Based upon cluster analysis of their chromosome profiles the majority of the
brewing contaminants could be grouped as either S. cerevisiae or S.
pastorianus/S. bayanus. Further, the technique was able to differentiate between
almost all brewing contaminants and to separate them from any specific lager
brewing yeast. The diversity of the Saccharomyces brewing contaminants clearly
demonstrated by their CLP was further reflected by MAL genotyping. For the
majority of the isolates more than two MAL loci were found with MAL1, MAL2 MAL3,
MAL4 and MAL11, MAL31, MAL41 as the dominant genotypes. For all isolates MAL11
and MAL31 were found whereas MAL61 only was found for one isolate. The high
number of MAL loci found in the SaccharomYces brewing contaminants indicate their
adaptation to a maltose-enriched environment.
PMID- 11014522
TI - Characterisation of yeast flora isolated from an artisanal Portuguese ewes'
cheese.
AB - The evolution of the yeast flora was studied for an artisanal semi-hard ewes'
cheese made from raw milk. Mean log10 yeast counts per gram of cheese body ranged
from 2.7 to 6.4, with the higher counts observed after a ripening period of 30
days. The yeast population decreased thereafter and, at the end of curing
process, reached values similar to those of the beginning. A total of 344 yeasts
strains were randomly isolated from the curd and cheese body during the 60 days
long ripening period. Esterase activity was common to almost all isolates (98%)
while proteolysis was observed in 12% of the total yeast population. The
proportion of strains with positive glucose fermentation increased from 21% in
the curd to 75% at the end of the ripening period. A total of 150 isolates
representative of the physiological characteristics tested were examined with the
API ID 32C system showing different degrees of quality of identification. Only
15% of the strains (23 isolates) were excellently identified being assigned to
the species Candida zeylanoides. The most frequent species appeared to be
Debaryomyces hansenii (anamorph Candida famata) and Candida intermedia. These two
species amounted to 9% of the yeasts in the curd increasing to 86% at the end of
the ripening period.
PMID- 11014523
TI - Selective enrichment broth for the isolation of Aeromonas sp. from chicken meat.
AB - Six selective agents (ampicillin, novobiocin, cephalothin, bile salts, brilliant
green and ethanol) were tested during the development of a selective enrichment
broth for the isolation of Aeromonas sp. from food. Cephalothin at 10 mg/l was
found to be the best selective agent owing to its greater selectivity and
efficiency in recovering stressed and lower cell concentrations of Aeromonas sp.
Higher concentrations (15-25 mg/l) of cephalothin were inhibitory to some strains
of A. sobria. Cephalothin (10 mg/l) was incorporated in buffered dextrin broth
(BCDB-10) and alkaline peptone water (CAPW-10) and employed for the isolation of
Aeromonas sp. from chicken meat naturally and artificially inoculated (with 10(9)
cells/ml of A. hydrophila). The highest isolation rate (22%) with naturally
contaminated chicken was achieved with CAPW-10 in comparison to 16% with BCDB-10
and 8% with APW. Similarly, from artificially inoculated samples, 100% isolation
was accomplished with CAPW-10, against 80% with BCDB-10 and 50% with APW.
PMID- 11014524
TI - Chemical, physical and enzymatic pre-treatments of probiotic lactobacilli alter
their adhesion to human intestinal mucus glycoproteins.
AB - Intestinal mucus glycoproteins extracted from faeces of healthy adult subjects
were used as a substratum for bacterial adhesion to investigate the effects of
physical, chemical and enzymatic pre-treatments of the bacteria on their
adhesion. The strains studied were Lactobacillus acidophilus 1 (LCI, Nestle), L.
rhamnosus strain GG (ATCC 53103), L. rhamnosus LC-705, and L. casei strain
Shirota (Yakult, Yakult Ltd). Hereafter the strains are referred to as LA1, LGG,
LC-705, and Shirota, respectively. Strains LA1 and LGG adhered greatly whereas
the adhesion of strains LC-705 and Shirota to intestinal mucus glycoproteins was
low. Adhesion of LA1 and LGG was reduced by boiling, autoclaving and by pepsin
and trypsin treatments suggesting that the bacterial protein structures are
essential for their adhesion. Treatment in ethanol and in propanol prior to
adhesion significantly increased the adhesion of LA1 and LC-705, respectively.
Adhesion of Shirota strain was not altered by any of the treatments.
PMID- 11014525
TI - Acid resistance of enterohaemorrhagic and generic Escherichia coli associated
with foodborne disease and meat.
AB - As part of the Australia New Zealand Food Authorities (ANZFA) food standards
code, salami manufacturers are required to demonstrate that their process is
capable of achieving a 3-log reduction in Escherichia coli. Non-pathogenic E.
coli strains with similar or greater acid resistance to enterohaemorrhagic E.
coli (EHEC) are needed if industry is to conduct challenge studies to demonstrate
compliance with the standard. In the present study, E. coli isolates from sheep
and beef carcasses and meat were shown to have wide-ranging acid resistance in
broth when preadapted to growth in acidic conditions. Times required for a 3-log
reduction in E. coli ranged from less than I day to more than 28 days. Variable
acid resistance was observed in both EHEC strains associated with foodborne
outbreaks and generic E. coli strains. Generic E. coli strains with the greatest
acid resistance were assessed for pathogenicity markers and their survival in
fermented meat compared with EHEC strains. It was demonstrated that generic E.
coli strains could be used for challenge studies to determine compliance with or
validate performance standards designed for the control of EHEC.
PMID- 11014526
TI - Cluster analysis, richness and biodiversity indexes derived from denaturing
gradient gel electrophoresis fingerprints of bacterial communities demonstrate
that traditional maize fermentations are driven by the transformation process.
AB - The bacterial communities of maize fermented foods (pozol, poto-poto and ogi)
from Mexico, Congo and Benin was compared using a culture-independent approach
[denaturing gradient gel electrophoresis (DGGE) analysis of total DNA]. Foods
produced following the same flow chart (i) grouped in distinct clusters, (ii)
shared similar richness and biodiversity indexes and (iii) exhibited a high intra
specific variability. Structural biodiversity was higher in pozol samples,
probably due to oxic conditions and higher initial pH. DGGE bands found in foods
of different origins suggest that Lactobacillus plantarum, Lb. delbrueckii and
Lb. fermentum are particularly well adapted to the fermentation of maize.
PMID- 11014527
TI - Phenotypic adaptation to freeze-thaw stress of the yeast-like fungus Geotrichum
candidum.
AB - The effect of cold stress on Geotrichum candidum was investigated at chill and
freezing temperatures. Specific growth rates were determined at various
temperatures and plotted according to the Ratkowsky and Arrhenius equations. The
obtained profiles led to the determination of characteristics including the
activation energy and notional minimum temperatures. At temperatures below the
optimum single linear slopes were observed. At freezing temperatures, the loss of
viability of cell populations was proportional to the number of freezing-thawing
cycles. Nevertheless, the ability of G. candidum to survive this challenge
depended on the physiological conditions prior to the freezing stress. The loss
of viability was growth phase specific. Cells harvested in stationary phase
showed a higher resistance compared to those obtained with cells in exponential
phase. Furthermore, the cells of G. candidum could be adapted to the freeze-thaw
challenge by pre-treatment at chill temperatures. This phenomenon known as
cryotolerance was a function of the duration of the preincubation exposure.
PMID- 11014528
TI - Detection of freeze-injured Escherichia coli O157:H7 cells from foods by
resuscitation prior to selective enrichment.
AB - We tried to detect Escherichia coli O157:H7 in food samples artificially
contaminated with freeze-injured E. coli O157:H7 using an enrichment method with
modified EC broth supplemented with novobiocin (mEC + n). When the samples were
cultured for enrichment immediately after inoculation of freeze-injured cells, E.
coli O157:H7 was not detected in 13 out of 18 samples. However, allowing the food
samples to stand for 3 h at room temperature prior to enrichment in mEC + n
remarkably improved recovery of E. coli O157:H7 except for some acidic foods. E.
coli O157:H7 was detected in the acidic foods by introducing a resuscitation step
of 3-h of incubation in a non-selective broth at room temperature prior to
enrichment with mEC + n.
PMID- 11014529
TI - Do women fare worse: a metaanalysis of gender differences in traumatic brain
injury outcome.
AB - OBJECT: The purpose of this metaanalysis was to investigate possible gender
differences in traumatic brain injury (TBI) sequelae. The case fatality rates in
patients after TBI have previously been shown to be significantly higher in women
as compared with men. METHODS: A quantitative review of published studies of TBI
outcome revealed eight studies (20 outcome variables) of TBI, in which outcome
was reported separately for men and women. CONCLUSIONS: Outcome was worse in
women than in men for 85% of the measured variables, with an average effect size
of -0.15. Although clinical opinion is often that women tend to experience better
outcomes than men after TBI, the opposite pattern was suggested in the results of
this metaanalysis. However, this conclusion is limited by the fact that, in only
a small percentage of the total published reports on TBI outcome, was outcome
described separately for each sex. A careful, prospective study of sex
differences in TBI outcome is clearly needed.
PMID- 11014530
TI - Effect of long-term mild hypothermia therapy in patients with severe traumatic
brain injury: 1-year follow-up review of 87 cases.
AB - OBJECT: The goal of this study was to investigate the protective effects of long
term (3-14 days) mild hypothermia therapy (33-35 degrees C) on outcome in 87
patients with severe traumatic brain injury (TBI) (Glasgow Coma Scale score < or
= 8). METHODS: In 43 patients assigned to a mild hypothermia group, body
temperatures were cooled to 33 to 35 degrees C a mean of 15 hours after injury
and kept at 33 to 35 degrees C for 3 to 14 days. Rewarming commenced when the
individual patient's intracranial pressure (ICP) returned to the normal level.
Body temperatures in 44 patients assigned to a normothermia group were maintained
at 37 to 38 degrees C. Each patient's outcome was evaluated 1 year later by using
the Glasgow Outcome Scale. One year after TBI, the mortality rate was 25.58% (11
of 43 patients) and the rate of favorable outcome (good recovery or moderate
disability) was 46.51% (20 of 43 patients) in the mild hypothermia group. In the
normothermia group, the mortality rate was 45.45% (20 of 44 patients) and the
rate of favorable outcome was 27.27% (12 of 44 patients) (p < 0.05). Induced mild
hypothermia also markedly reduced ICP (p < 0.01) and inhibited hyperglycemia (p <
0.05). The rates of complication were not significantly different between the two
groups. CONCLUSIONS: The data produced by this study demonstrate that long-term
mild hypothermia therapy significantly improves outcomes in patients with severe
TBI.
PMID- 11014531
TI - Risk of rupture from incidental cerebral aneurysms.
AB - OBJECT: Controversy still exists about the risk estimation for rupture of
untreated saccular aneurysms presenting for causes other than subarachnoid
hemorrhage (SAH). The object of this study was to address this issue. METHODS:
Between January 1976 and December 1997 in the Aizu Chuou Hospital, 62 patients
underwent observation for more than 6 months for saccular, nonthrombotic,
noncalcified unruptured aneurysms at locations not related to the cavernous
sinus, which were detected in cerebral angiography studies performed for causes
other than SAH. Clinical follow-up data in those 62 patients were reviewed to
identify the risk of SAH. All patients were followed until July 1998, with the
observation period ranging from 6 months to 17 years (mean 4.3 years). Seven
patients (11.3%) developed SAH confirmed on computerized tomography (CT) scanning
at a mean interval of 4.8 years, six of whom died and one of whom recovered with
a major deficit. In addition, one patient died of the mass effect of the
aneurysm, and another after sudden onset of headache and vomiting. The 5- and 10
year cumulative risks of CT-confirmed SAH calculated by the Kaplan-Meier method
were 7.5% and 22.1%, respectively, for total cases, 33.5% and 55.9%,
respectively, for large (> 10 mm) aneurysms, and 4.5% and 13.9%, respectively,
for small (< 10 mm) aneurysms. CONCLUSIONS: Although based on a relatively small,
single-institution series, our data indicated that the risk of rupture from
incidental, intradural, saccular aneurysms was higher than previously reported,
and may support preventive surgical treatment of incidental aneurysms,
considering the fatality rate of SAH.
PMID- 11014532
TI - Intraoperative endovascular treatment as an adjunct to microsurgical clipping of
paraclinoid aneurysms.
AB - OBJECT: The endovascular procedure can provide proximal control, suction
decompression, and prompt intraoperative angiography during microsurgical
clipping of aneurysms of the paraclinoid segment of the internal carotid artery
(ICA). The authors assess the safety and feasibility of this method in 24
consecutive cases. METHODS: Frontotemporal craniotomy and radical pterionectomy
were performed with the patient's head immobilized in a radiolucent frame while
femoral artery catheterization was achieved. Before dural opening, a balloon
catheter with a coaxial lumen was positioned and tested in the ICA, after which
microsurgical exposure was completed, including intradural clinoid drilling and
optic canal decompression. Trapping of the lesion was achieved by inflating the
balloon and placing a temporary clip beyond the aneurysm neck. The catheter was
gently aspirated to achieve suction decompression and to facilitate clip
application. Intraoperative digital subtraction angiography was then performed.
Twenty-two aneurysms were larger than 10 mm, and 11 of them were giant. Six
patients presented with subarachnoid hemorrhage and nine with visual symptoms.
Balloon occlusion and suction decompression were performed in 16 cases (67%), and
proximal control alone in 1 case. Intraoperative angiography was performed in
every case. Subsequent clip readjustment was necessary in seven cases, including
three cases of residual aneurysm filling and four of ICA compromise. Complete
aneurysm obliteration was achieved in 20 cases, and greater than 90% obliteration
in 22. One major infarct likely related to catheter thromboembolism was found.
There were no instances of visual deterioration or other complications
attributable to the endovascular procedure. CONCLUSIONS: The endovascular method
allows safe and reliable proximal control, suction decompression, and
intraoperative angiography in microsurgical treatment of large paraclinoid
aneurysms.
PMID- 11014533
TI - Natural history of the neck remnant of a cerebral aneurysm treated with the
Guglielmi detachable coil system.
AB - OBJECT: The long-term durability of Guglielmi detachable coil (GDC) embolization
of cerebral aneurysms is still unknown. The purpose of this study was to evaluate
the anatomical evolution of neck remnants in aneurysms treated with GDCs.
METHODS: Of 455 aneurysms treated with GDCs from 1990 to 1998 at the University
of California at Los Angeles Medical Center, 178 aneurysms (39%) had residual
necks postembolization. Long-term follow-up angiograms were obtained in 73 of
these aneurysms in 71 patients. The mean duration of angiographic follow up was
17.3 months. Twenty-four of the aneurysms were small with small necks, 24 were
small with wide necks, 15 were large, and 10 were giant aneurysms. In small
aneurysms with small necks, postembolization angiography revealed 12 aneurysms
(50%) with progressive thrombosis, eight (33%) unchanged, and four (17%) with
recanalization. In small aneurysms with wide necks, six (25%) had progressive
thrombosis, eight (33%) remained unchanged, and 10 (42%) had recanalization. In
large aneurysms, two (13%) were unchanged and 13 (87%) had recanalization. Of the
giant aneurysms only one (10%) remained unchanged and nine (90%) had
recanalization. Overall, 18 aneurysms (25%) exhibited progressive thrombosis, 19
(26%) remained unchanged, and 36 (49%) displayed recanalization on follow-up
angiography. During the last 2 years of the study, the recanalization rate
decreased and a higher rate of progressive thrombosis was noted in aneurysms with
small necks. These positive changes are related to important new technical
developments. CONCLUSIONS: Treatment with GDCs appears to be effective and the
results permanent in most small aneurysms with small necks. However, there are
important technical limitations in the current GDC technology that prevent
recanalization in wide-necked or large or giant aneurysms.
PMID- 11014534
TI - Impact of Guglielmi detachable coils on outcomes of patients with intracranial
aneurysms treated by a multidisciplinary team at a single institution.
AB - OBJECT: The goal of this study was to investigate the impact of the introduction
of the Guglielmi detachable coil (GDC) therapeutic option on the overall
management outcome of intracranial aneurysms. The authors accomplished this by
assessing patient morbidity and mortality, inflation-adjusted hospital charges,
lengths of stay in the hospital and the intensive care unit (ICU), and treatment
efficacy. METHODS: The authors conducted a retrospective analysis of consecutive
cases of intracranial intradural aneurysms managed by a single multidisciplinary
neurovascular team at a tertiary care, academic referral center during the 24
months preceding the introduction of the GDC procedure (Group I or pre-GDC era,
77 patients) and during the first 24 months after its introduction (Group II or
GDC era, 99 patients). Treatment with GDCs was considered for cases of higher
clinical grade or poor surgical risk, or in response to patient preference (27
[27%] of 99 patients in Group II). Host and lesion parameters in our cohort were
validated against outcome parameters by using univariate and multivariate
analyses. The pre-GDC and GDC subgroups of patients were comparable for major
disease severity parameters (patient age, lesion location, clinical grade, and
hemorrhage severity). There was no significant difference in clinical outcome at
6 months, infarcts on computerized tomography scanning, or aneurysm obliteration
rates before and after introduction of GDC treatment. Decreasing trends in
duration of hospital and ICU stay and in inflation-adjusted hospital charges
occurred well before and thus were unrelated to the introduction of the GDC
therapeutic option. CONCLUSIONS: The results of this study do not demonstrate any
significant impact of integration of the GDC modality on clinical outcome,
mortality, morbidity, or effectiveness of treatment. Ongoing improvements in
hospital charges and length of hospital stay appeared unrelated to the
introduction of the GDC option.
PMID- 11014535
TI - Change in circulating blood volume following craniotomy.
AB - OBJECT: The importance of monitoring circulating blood volume (CBV) during
perioperative management is widely recognized in critically ill patients. The
purpose of this study was to investigate the change in CBV following craniotomy
by using indocyanine-green pulse spectrophotometry. METHODS: Circulating blood
volume and plasma hormones related to stress and fluid regulation were measured
five times: preoperatively, immediately postoperatively, and 1, 2, and 7 days
after craniotomy was performed in 17 patients with a brain tumor or an unruptured
aneurysm. The mean value of CBV preoperatively was 82 ml/kg, which decreased to
64 ml/kg (78%) immediately postoperatively and gradually recovered to 82 ml/kg on
Day 7 postsurgery (p = 0.0069). The mean values of adrenaline, noradrenaline,
arginine vasopressin, renin, and aldosterone were highest immediately
postoperatively. The mean intraoperative balances of water and sodium were 1,090
ml and 113 mEq, respectively. Partial correlation coefficients of CBV to
noradrenaline and serum sodium during the entire study were -0.430 (p = 0.0036)
and 0.418 (p = 0.0048), respectively. CONCLUSIONS: Attention should be paid to
decreased CBV following craniotomy, which is caused by the shift of fluid to
interstitial spaces due to surgical stress. Hypovolemia can be suspected from a
postoperative decrease in serum sodium.
PMID- 11014536
TI - Continuous electromyography monitoring of motor cranial nerves during
cerebellopontine angle surgery.
AB - OBJECT: Electromyography (EMG) monitoring is expected to reduce the incidence of
motor cranial nerve deficits in cerebellopontine angle surgery. The aim of this
study was to provide a detailed analysis of intraoperative EMG phenomena with
respect to their surgical significance. METHODS: Using a system that continuously
records facial and lower cranial nerve EMG signals during the entire operative
procedure, the authors examined 30 patients undergoing surgery on acoustic
neuroma (24 patients) or meningioma (six patients). Free-running EMG signals were
recorded from muscles targeted by the facial, trigeminal, and lower cranial
nerves, and were analyzed off-line with respect to waveform characteristics,
frequencies, and amplitudes. Intraoperative measurements were correlated with
typical surgical maneuvers and postoperative outcomes. Characteristic EMG
discharges were obtained: spikes and bursts were recorded immediately following
the direct manipulation of a dissecting instrument near the cranial nerve, but
also during periods when the nerve had not yet been exposed. Bursts could be
precisely attributed to contact activity. Three distinct types of trains were
identified: A, B, and C trains. Whereas B and C trains are irrelevant with
respect to postoperative outcome, the A train--a sinusoidal, symmetrical sequence
of high-frequency and low-amplitude signals--was observed in 19 patients and
could be well correlated with additional postoperative facial nerve paresis (in
18 patients). CONCLUSIONS: It could be demonstrated that the occurrence of A
trains is a highly reliable predictor for postoperative facial palsy. Although
some degree of functional worsening is to be expected postoperatively, there is a
good chance of avoiding major deficits by warning the surgeon early. Continuous
EMG monitoring is superior to electrical nerve stimulation or acoustic
loudspeaker monitoring alone. The detailed analysis of EMG-waveform
characteristics is able to provide more accurate warning criteria during surgery.
PMID- 11014537
TI - Role of hydrodynamic processes in the pathogenesis of peritumoral brain edema in
meningiomas.
AB - OBJECT: In a prospective study, 28 patients with 32 intracranial meningiomas were
examined to determine the role of hydrodynamic interaction between tumor and
surrounding brain tissue in the pathogenesis of peritumoral brain edema. METHODS:
Gadolinium-diethylenetriamine pentaacetic acid (Gd-DPTA), an extracellular
contrast agent used for routine clinical imaging, remains strictly extracellular
without crossing an intact blood-brain barrier. Therefore, it is well suited for
investigations of hydrodynamic extracellular mechanisms in the development of
brain edema. Spin-echo T1-weighted magnetic resonance images were acquired before
and after intravenous administration of 0.2 mmol/kg Gd-DPTA. Additional T1
weighted imaging was performed 0.6, 3.5, and 6.5 hours later. No significant Gd
DPTA diffused from tumor into peritumoral brain tissue in 12 meningiomas without
surrounding brain edema. In contrast, in 17 of 20 meningiomas with surrounding
edema, contrast agent in peritumoral brain tissue was detectable after 3.5 hours
and 6.5 hours. In three of 20 meningiomas with minimum surrounding edema (<5
cm3), contrast agent effusion was absent. After 3.5 hours and 6.5 hours strong
correlations of edema volume and the maximum distance of contrast spread from the
tumor margin into adjacent brain parenchyma (r = 0.84 and r = 0.87, respectively,
p < 0.0001) indicated faster effusion in larger areas of edema. CONCLUSIONS: The
results of this study show that significant contrast agent effusion from the
extracellular space of the tumor into the interstitium of the peritumoral brain
tissue is only found in meningiomas with surrounding edema. This supports the
hypothesis that hydrodynamic processes play an essential role in the pathogenesis
of peritumoral brain edema in meningiomas.
PMID- 11014539
TI - Posture-related changes in the pressure environment of the ventriculoperitoneal
shunt system.
AB - OBJECT: The purpose of this study is to clarify the whole pressure environment of
the ventriculoperitoneal (VP) shunt system in patients with successfully treated
hydrocephalus and to determine which factor of the pressure environment has a
preventive effect on overdrainage. METHODS: Thirteen patients with hydrocephalus
who had been treated with VP shunt therapy by using a Codman-Hakim programmable
valve without incidence of overdrainage were examined. The authors evaluated
intracranial pressure (ICP), intraabdominal pressure (IAP), hydrostatic pressure
(HP), and the perfusion pressure (PP) of the shunt system with the patients both
supine and sitting. With patients supine, ICP, IAP, and HP were 4.6 +/- 3 mm Hg,
5.7 +/- 3.3 mm Hg, and 3.3 +/- 1 mm Hg, respectively. As a result, the PP was
only 2.2 +/- 4.9 mm Hg. When the patients sat up, the IAP increased to 14.7 +/-
4.8 mm Hg, and ICP decreased to-- 14.2 +/- 4.5 mm Hg. The increased IAP and
decreased ICP offset 67% of the HP (42.9 +/- 3.5 mm Hg), and consequently the PP
(14 +/- 6.3 mm Hg) corresponded to only 33% of HP. CONCLUSIONS: The results
observed in patients indicated that IAP as well as ICP play an important role in
VP shunt therapy and that the increased IAP and the decreased ICP in patients
placed in the upright position allow them to adapt to the siphoning effect and
for overdrainage thereby to be avoided.
PMID- 11014538
TI - Prognostic factors in intracranial ependymomas in children.
AB - OBJECT: The occurrence of intracranial ependymomas in children is relatively
infrequent, and their prognostic factors are still controversial, especially
regarding histological composition. METHODS: A retrospective study was conducted
of 37 children treated during the last 20 years for intracranial ependymomas at
the Hopital de la Timone. Both univariate and multivariate statistical analyses
were performed to assess the prognostic relevance of patient age and sex, extent
of tumor removal, location of the tumor (supratentorial compared with
infratentorial, median compared with lateral), tumor histological composition,
and adjuvant therapies in affecting the 5-year progression-free survival (PFS)
rate and overall survival (OS) rate. The following histopathological features,
either alone or in combination, were analyzed: endothelial proliferation,
necrosis, loss of differentiating structures (present compared with absent), the
number of mitotic figures per 10 hpf, and cellularity (number of nuclei/5 hpf).
In addition, immunohistochemical detection of Ki-67 antigen was performed and the
Ki-67 labeling index (LI) evaluated in all cases. The 5-year OS and PFS rates
were 45% and 25%, respectively (median follow up 34 months). Four patients died
of disease without remission (median 163 days) and disease in 21 patients
relapsed: 18 in situ and three both in situ and distantly. On univariate analysis
total surgical resection and median infratentorial location were associated with
a better outcome (p < 0.002) for both OS and PFS. Loss of differentiating
structures was associated with poor prognosis (p < 0.008) and the combination of
necrosis, endothelial proliferation, and mitotic index greater than 5 was also a
negative predictive factor for both OS (p < 0.002) and PFS (p = 0.02). The PFS
time was shorter in patients younger than 4 years of age and in patients in whom
a Ki-67 LI greater than 1 was found (p = 0.03 and 0.006, respectively). Adjuvant
radiotherapy and chemotherapy were not relevant to prognosis. Moreover, among the
15 patients in whom total excision was achieved, OS was better in those who did
not receive adjuvant therapies. In contrast, adjuvant therapies significantly
enhanced PFS time in patients in whom tumor excision was incomplete. CONCLUSIONS:
This study and analysis of the literature further highlight that total tumor
removal is the treatment of choice for ependymomas in children. Postoperative
measurement of residual tumor is required, especially because a subgroup of
patients might be treated by surgery alone. Median infratentorial ependymomas
have to be distinguished from the lateral type. Appropriate and reproducible
histological parameters and Ki-67 LI are of interest as predictors of outcome.
PMID- 11014540
TI - Telomerase activity in primary and secondary glioblastomas multiforme as a novel
molecular tumor marker.
AB - OBJECT: Telomerase activity is responsible for cell immortality. To examine the
role of telomerase in the carcinogenesis of human glioblastomas multiforme
(GBMs), the authors studied telomerase activity, telomerase component expression,
and telomere lengths in 42 GBM samples. METHODS: In all samples, EGFR and MDM2
amplifications and overexpressions were examined using Southern and Northern blot
analyses. The p53 mutation was analyzed using polymerase chain reaction-single
strand conformational polymorphism and by direct sequence analysis. Specimens of
tissues were immunostained with p53, EGFR, and MDM2 antibodies. Allelic loss on
chromosomes 17p and 10 was assessed by loss of heterozygosity (LOH) assays.
Telomerase activity, expression of its components (human telomerase reverse
transcriptase [hTERT], human telomerase RNA component [hTERC], and telomerase
associated protein [TEP1]), and telomere lengths were analyzed using the
telomeric repeat amplification protocol (TRAP)-hybridization protection assay,
reverse transcription-polymerase chain reaction, and Southern blot analysis.
According to the results of assessments of EGFR and MDM2 amplifications, p53
mutation, LOHs in chromosomes 17p and 10, and the clinical course of the disease,
the 42 samples were classified into 22 primary and 20 secondary glioblastomas.
Twenty-six (61.9%) of all 42 samples demonstrated detectable telomerase activity
during the TRAP assay. Secondary GBMs displayed significantly higher levels of
telomerase activity and hTERT expression than primary GBMs. Tumors with a p53
gene mutation demonstrated significantly higher telomerase activity than those
without a p53 mutation. Four samples with a codon 175 mutation demonstrated an
exceptionally high amount of telomerase activity. In secondary GBMs, the increase
in telomerase activity and the hTERT expression level correlated with the
increased frequency of p53 mutations. There was no significant difference in
telomere length between primary and secondary GBMs. CONCLUSIONS: These results
suggest that telomerase activity and p53 mutations both play important roles in
the multistep carcinogenesis of GBMs. Telomerase activity and hTERT expression
may be considered as novel distinctive factors in human GBMs.
PMID- 11014541
TI - Diffuse axonal injury due to lateral head rotation in a rat model.
AB - OBJECT: The authors investigated the ramifications of producing diffuse axonal
injury (DAI) by lateral head rotation in a rat model. METHODS: Using a special
injury-producing device, the rat's head was rapidly rotated 90 degrees in the
coronal plane at an angular velocity of at least 753.13 rad/second and an angular
acceleration of at least 1.806 x 10(5) rad/second2; the rotation was complete
within 2.09 msec. There were no statistically significant changes in PO2, PCO2,
pH, or blood pressure values at 5, 15, or 60 minutes after head rotation compared
with their respective preinjury baseline values. The rats exhibited posttraumatic
behavior suppression for an average of 12.6 minutes. The mortality rate was 17%.
The rats that survived had diffuse subarachnoid hemorrhage around the brainstem
and upper cervical cord, but no obvious brain contusion. In sections stained with
silver or hematoxylin and eosin, axonal swelling and bulblike protrusions at the
axonal axis were observed in the medulla oblongata, midbrain, upper cervical
cord, and corpus callosum between 6 hours and 144 hours postinjury. The axonal
injuries were most severe in the brainstem and were accompanied by parenchymal
bleeding. The density of bulblike axonal protrusions peaked 6 hours postinjury in
the medulla oblongata and 24 hours postinjury in the midbrain. CONCLUSIONS: Rapid
lateral head rotation can produce DAI characterized by severe damage to the rat
brainstem.
PMID- 11014542
TI - Dexamethasone-induced abolition of the inflammatory response in an experimental
glioma model: a flow cytometry study.
AB - OBJECT: Commonly used for management of cerebral edema in patients with brain
tumors, steroid medications also have immunosuppressive functions. To
characterize the effects of steroids on the central nervous system's response to
tumors more clearly, flow cytometry was used to quantify the extent of
inflammatory cell infiltration in an immunogenic rat glioma model. METHODS:
Freshly prepared 11-day-old intracranial C6 tumors that had been excised from
dexamethasone-treated and untreated rats were labeled ex vivo with monoclonal
antibodies against CD 11b/c, CD45, and CD8a antigens. The extent of microglia
(CD11b/c-highly positive, CD45-slightly positive cell), macrophage (CD11b/c
highly positive, CD45-highly positive cell), lymphocyte (CD11b/c-negative, CD45
highly positive cell), and cytotoxic T-cell (CD8a-positive cell) infiltration
into each rat's tumor, tumor periphery, and contralateral tumor-free hemisphere
was analyzed using flow cytometry. Microglia and lymphocytes constituted a
significant component of infiltrating cells in this model, comprising 23 +/- 3%
and 33 +/- 5% of viable cells, respectively. Macrophages, on the other hand,
accounted for only 9 +/- 1% of infiltrating cells. Treatment of rats with a 7-day
course of low-dose dexamethasone (0.1 mg/kg/day) resulted in a greater than 50%
inhibition of microglia (p = 0.03) and lymphocyte (p = 0.001) infiltration into
tumors. Increasing the dexamethasone dose to 1 mg/kg/day further abolished
lymphocyte infiltration (89% inhibition, p = 0.001) but had no additional
inhibitory effect on microglia invasion. Macrophage infiltration of tumors was
not inhibited at the dexamethasone doses used in this study (p = 0.42).
CONCLUSIONS: Flow cytometry is a valuable technique for characterizing tumor
associated inflammatory cells in gliomas. Even at low doses, dexamethasone was
found to inhibit significantly the infiltration of brain tumors by lymphocytes
and microglia. These findings should be considered when experimental
immunotherapeutic strategies are evaluated for clinical application.
PMID- 11014543
TI - Role of calcium channels in oxyhemoglobin-induced apoptosis in endothelial cells.
AB - OBJECT: Oxyhemoglobin (OxyHb) released from hemolysed erythrocytes has been
considered to be responsible for cerebral vasospasm after subarachnoid
hemorrhage. The authors previously reported that OxyHb produced apoptosis in
cultured vascular endothelial cells. The change in intracellular Ca++ homeostasis
was expected to be one of the possible mechanisms of the cytotoxic effects of
OxyHb. This study was undertaken to investigate the protective effects of Ca++
channel blockers on OxyHb-induced apoptosis. METHODS: Cultured bovine coronary
artery and brain microvascular endothelial cells (passages 5-9) were used. A cell
density study, immunohistochemical staining, and DNA fragmentation analysis were
performed to confirm apoptosis. Various concentrations (1-50 microM) of OxyHb
were used for 24- to 72-hour incubations with and without Ca++-channel blockers.
Oxyhemoglobin produced cytotoxicity leading to cell detachment from the culture
dish in time- and concentration-dependent manners. The highest dose (50 microM)
of OxyHb produced cell detachment after a 24-hour incubation, and the lower doses
(1-10 microM) produced cell detachment after 48 to 72 hours. Immunohistochemical
analysis showed that apoptosis occurred in cells that were still attached to the
side of the culture dish after 48 to 72 hours of OxyHb treatment (5 microM). The
OxyHb (10 microM) produced DNA ladders at 48 to 72 hours. Three Ca++-channel
blockers were used to prevent the toxic effect of OxyHb. The voltage-dependent
Ca++-channel blocker nicardipine (1 microM), the voltage-independent Ca++-channel
blocker econazole (10 microM), and the inorganic Ca++-channel blocker lanthanum
(100 microM) all failed to prevent cell detachment or DNA ladders produced by
OxyHb. These results were similar in both cell lines. CONCLUSIONS: Oxyhemoglobin
produced apoptotic changes in cultured vascular endothelial cells, and Ca++
channel blockers did not prevent OxyHb-induced apoptosis.
PMID- 11014544
TI - Relationship between residual cerebral blood flow and oxygen metabolism as
predictive of ischemic tissue viability: sequential multitracer positron emission
tomography scanning of middle cerebral artery occlusion during the critical first
6 hours after stroke in pigs.
AB - OBJECT: The authors tested the hypothesis that oxygen metabolism is the key
factor linking the long-term viability of ischemic brain tissue to the magnitude
of residual blood flow during the first 6 hours following a stroke. METHODS:
Eleven anesthetized pigs underwent a series of positron emission tomography
studies to measure cerebral blood flow (CBF) and metabolism before and for 7
hours after the animals were subjected to permanent middle cerebral artery (MCA)
occlusion. The extent of collateral blood supply was assessed using angiography.
Abnormal metabolism of the ischemic tissue progressed as a function of time in
inverse proportion to the magnitude of residual CBF, and the volume of the
infarct grew in inverse proportion to the residual blood supply. Ten hours after
occlusion of the MCA, the infarct topographically matched the tissue with a
cerebral metabolic rate of oxygen consumption below 50% of values measured on the
contralateral side. This was also the threshold for the decline of the oxygen
extraction fraction below normal, which was critical for the prediction of
nonviable ischemic tissue. Mildly ischemic tissue (CBF > 30 ml/100 g/min) did not
reach the cerebral metabolic rate of oxygen threshold of viability during the
first 6 hours after MCA occlusion; moderately ischemic tissue (CBF 12-30 m1/100
g/ min) reached the threshold of viability in 3 hours; and severely ischemic
tissue (CBF < 12 ml/100 g/min) remained viable for less than 1 hour. CONCLUSIONS:
The relationship between the residual CBF and both oxygen metabolism and
extraction is critical to the evolution of metabolic deficiency and lesion size
after stroke.
PMID- 11014545
TI - Products of hemolysis in the subarachnoid space inducing spreading ischemia in
the cortex and focal necrosis in rats: a model for delayed ischemic neurological
deficits after subarachnoid hemorrhage?
AB - OBJECT: The pathogenesis of delayed ischemic neurological deficits after
subarachnoid hemorrhage has been related to products of hemolysis. Topical brain
superfusion of artificial cerebrospinal fluid (ACSF) containing the hemolysis
products K+ and hemoglobin (Hb) was previously shown to induce ischemia in rats.
Superimposed on a slow vasospastic reaction, the ischemic events represent
spreading depolarizations of the neuronal-glial network that trigger acute
vasoconstriction. The purpose of the present study was to investigate whether
such spreading ischemias in the cortex lead to brain damage. METHODS: A cranial
window was implanted in 31 rats. Cerebral blood flow (CBF) was measured using
laser Doppler flowmetry, and direct current (DC) potentials were recorded. The
ACSF was superfused topically over the brain. Rats were assigned to five groups
representing different ACSF compositions. Analyses included classic histochemical
and immunohistochemical studies (glial fibrillary acidic protein and ionized
calcium binding adaptor molecule) as well as a terminal deoxynucleotidyl
transferase-mediated deoxyuridine triphosphate nick-end labeling assay.
Superfusion of ACSF containing Hb combined with either a high concentration of K+
(35 mmol/L, 16 animals) or a low concentration of glucose (0.8 mmol/L, four
animals) reduced CBF gradually. Spreading ischemia in the cortex appeared when
CBF reached 40 to 70% compared with baseline (which was deemed 100%). This
spreading ischemia was characterized by a sharp negative shift in DC, which
preceded a steep CBF decrease that was followed by a slow recovery (average
duration 60 minutes). In 12 of the surviving 14 animals widespread cortical
infarction was observed at the site of the cranial window and neighboring areas
in contrast to findings in the three control groups (11 animals). CONCLUSIONS:
The authors conclude that subarachnoid Hb combined with either a high K+ or a low
glucose concentration leads to widespread necrosis of the cortex.
PMID- 11014546
TI - Microanatomy of the pericallosal arterial complex.
AB - OBJECT: The pericallosal arterial complex supplies the callosal and pericallosal
regions, as well as the anterior two thirds of the medial and superomedial
aspects of both hemispheres. It is composed of the pericallosal artery (that is,
the segment of the anterior cerebral artery located distal to the anterior
communicating artery [ACoA]) and the median callosal artery (or third
pericallosal artery), which originates from the ACoA. This system was studied in
46 specimens (23 human cadaver heads) injected with colored latex. METHODS: After
being injected with colored latex, embalmed, and bleached, the specimens were
studied with the aid of optic magnification. The pericallosal artery was found to
be divided into four segments (A2-A5 in the proximodistal direction). After
giving rise to central, callosal, and cortical branches, it terminated near the
splenium of the corpus callosum as the posterior pericallosal artery, or on the
precuneus as the inferomedial parietal artery. CONCLUSIONS: The authors propose a
logical classification of the different variations in the pericallosal arterial
complex based on embryological development. This complex can be considered a
hemodynamic solution to an abnormal regression of one of its parts, which is
balanced by the development of supplemental channels from other parts.
PMID- 11014547
TI - Optical imaging of bilingual cortical representations. Case report.
AB - The organization of language in the brains of multilingual persons remains
controversial. The authors investigated language representations in a proficient
bilingual patient by using a novel neuroimaging technique, intraoperative optical
imaging of intrinsic signals (iOIS), and a visual object naming task. The results
indicate that there are cortical areas that are activated by the use of both
English and Spanish languages (superior temporal sulcus, superior and middle
temporal gyri, and parts of the supramarginal gyrus). In addition, language
specific areas were identified in the supramarginal (Spanish) and precentral
(English) gyri. These results suggest that cortical language representations in
bilingual persons may consist of both overlapping and distinct components.
Furthermore, this study demonstrates the utility of iOIS in detecting
topographical segregation of cognitively distinct cortices.
PMID- 11014548
TI - Ependymal cyst producing alpha-fetoprotein. Case report.
AB - This 17-year-old man was admitted to the hospital due to progressive headache and
diplopia. Neuroradiological studies revealed a cystic mass in the pineal region
without a parenchymal lesion. In addition, serum alpha-fetoprotein (AFP) levels
were elevated. A cyst-to-third-ventricle and cistern fenestration was performed,
but the cyst enlarged 3 months after the first operation. In the second
operation, subtotal resection of the cyst was performed. The AFP level in the
cyst fluid was very high preoperatively but was decreased postoperatively. The
patient was discharged with no neurological deficit. Pathological examination of
resected tissue showed a single layer of cuboidal cells that resembled an
ependymal structure. The cells were immunoreactive for AFP immunostain, which
indicated AFP production from these cells.
PMID- 11014549
TI - Middle meningeal artery embolization for refractory chronic subdural hematoma.
Case report.
AB - The authors present a case of refractory chronic subdural hematoma (CSH) in a 59
year-old man with coagulopathy due to liver cirrhosis. The patient was
successfully treated by embolization of the middle meningeal artery after several
drainage procedures. This new therapeutic approach to recurrent CSH is discussed.
PMID- 11014550
TI - Treatment of spontaneous carotid-cavernous fistula in Ehlers-Danlos syndrome by
transvenous occlusion with Guglielmi detachable coils. Case report and review of
the literature.
AB - The authors report on a young woman with Ehlers-Danlos syndrome (EDS) Type IV in
whom a spontaneous direct carotid-cavernous fistula (CCF) was treated by
transvenous occlusion with regular and fiber-coated Guglielmi detachable coils.
To the authors' knowledge, this is the first time this approach has been used in
a patient with EDS. The different treatment options are discussed, and the
literature on endovascular treatment of direct CCFs in EDS is reviewed.
PMID- 11014551
TI - Synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome presenting as a
primary calvarial lesion. Case report and review of the literature.
AB - The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a
recently described, currently evolving clinical entity that groups together
several idiopathic disorders of bone and skin formerly described under a variety
of names. Among the spectrum of possible locations for the bone lesions, there is
no previous report in the literature of primary involvement of the skull vault. A
patient with primary involvement of the calvaria in the setting of SAPHO syndrome
is described here, which, to the authors' knowledge, is the first report of such
localization. The clinically and radiologically benign evolution of the different
stages of the bone lesions is presented. The authors suggest that the SAPHO
syndrome should be considered in the differential diagnosis of lytic, sclerotic,
or hyperostotic lesions of the skull, particularly before considering invasive
diagnostic procedures.
PMID- 11014552
TI - Neuroblastomatous recurrence of ganglioglioma. Case report.
AB - This case is believed to be the first reported recurrent intracranial
ganglioglioma with purely neuroblastomatous malignant transformation. A complete
macroscopic resection of a right frontal lobe tumor in an 18-year-old woman
revealed differentiated ganglioglioma. Seven years later a large, well-demarcated
recurrent tumor was again macroscopically totally resected in the same patient.
Histological analysis showed malignant transformation in only the neuronal
component of the original tumor. A review of the literature on recurrent
gangliogliomas and their malignant transformation is included.
PMID- 11014553
TI - Multicentric intracranial smooth-muscle tumor in a woman with human
immunodeficiency virus. Case report.
AB - A 31-year-old woman with acquired immunodeficiency syndrome (AIDS) was found to
harbor both a pulmonary smooth-muscle tumor and an intracranial extraaxial smooth
muscle tumor of the parasellar region. The frequency of smooth-muscle tumors
(leiomyoma and leiomyosarcoma) has increased with AIDS, but much more so in
children than in adults. Only nine cases of human immunodeficiency virus-related
smooth-muscle tumors have been previously reported in adults, and only one of
these was located intracranially.
PMID- 11014554
TI - Electrophysiological localization of the substantia nigra in the parkinsonian
nonhuman primate.
AB - During ablative surgery and implantation of deep-brain stimulators for the
treatment of movement disorders, electrophysiological techniques are often used
for localization of subcortical targets. New restorative therapies for Parkinson
disease, aimed at delivering drugs or cells to the substantia nigra (SN), are
becoming available. Therefore, precise surgical approaches to the dopaminergic
cell-containing region of the SN are required to avoid damage to nearby
structures such as the corticospinal tract and subthalamic nucleus. In a study
conducted in nonhuman primates, the authors evaluated the utility and accuracy of
electrophysiological techniques in localizing the SN. Three adult rhesus monkeys
were used as hosts for intranigral cell transplants. The monkeys were rendered
hemiparkinsonian by intracarotid injection of 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine. With the aid of stereotactic guidance, chronic recording
chambers were placed on the skull of each monkey and directed at the SN. In each
monkey, 20 to 40 trajectories were explored with a microelectrode. Spontaneous
and movement-related single-unit activities were recorded in the SN, pars
reticulata, subthalamic nucleus, globus pallidus, striatum, thalamus, and red
nucleus. Motor and ocular responses to microstimulation in the subthalamic area
were noted. Using the electrophysiological and stereotactic information that was
obtained, three-dimensional maps of the nigral complex were constructed to infer
the location of the SN pars compacta. The maps were subsequently used to guide
intranigral placement of fetal dopaminergic cells. Accurate delivery was verified
by histological analysis. Based on the characteristic electrophysiological
properties of the SN and surrounding structures in the parkinsonian state,
microelectrode recording techniques may be used to ensure accurate placement of
cell transplantation in the intranigral region.
PMID- 11014555
TI - Use of titanium mesh for reconstruction of large anterior cranial base defects.
AB - The authors evaluated the role of titanium mesh used in combination with
vascularized pericranium to provide rigid support during reconstruction of
anterior skull base defects. Thirteen patients with large anterior skull base
defects caused by tumor invasion or traumatic injury involving the cribriform
plate, orbital roof, and planum sphenoidale were included in the study. The
reconstruction technique involved placement of titanium mesh between two layers
of continuous vascularized pericranium. Surgical glue and routine lumbar
cerebrospinal fluid (CSF) drainage were not used in any patient. At a mean
postoperative follow-up time of 22 months (range 8-39 months), none of the
patients had developed infection or meningocele. Postoperative CSF rhinorrhea
occurred in two patients with extensive dural defects, which resolved with
temporary lumbar drainage. Use of titanium mesh and a two-layer vascularized
pericranial graft is a safe, reproducible, and feasible method for reconstructing
the anterior skull base. Patients with large dural defects may need temporary CSF
diversion to avoid postoperative fistula formation.
PMID- 11014556
TI - Intracranial oculomotor nerve rhabdomyoma.
PMID- 11014557
TI - Anaplastic astrocytoma invading the optic chiasm through the optic pathway.
PMID- 11014558
TI - Hypothermia and severe brain injury.
PMID- 11014559
TI - Effect of Guglielmi detachable coils on aneurysm management.
PMID- 11014560
TI - Ependymomas in children.
PMID- 11014561
TI - Nodular medulloblastoma.
PMID- 11014562
TI - Cochlear region of the brainstem.
PMID- 11014563
TI - Keratin pearls.
PMID- 11014564
TI - Genetic classification of combined hepatocellular-cholangiocarcinoma.
AB - Combined hepatocellular-cholangiocarcinoma (combined HCC/ CC) is a rare form of
liver neoplasms showing both hepatocellular (HCC) and bile duct differentiation
(CC). In an attempt to clarify the clonality and genetic/phenotypic relationships
in the evolution of these neoplasms, we microdissected multiple HCC and CC foci
and studied allelic status of chromosome arms 1p, 1q, 3p, 4q, 5q, 6q, 8p, 9p,
10q, 11q, 13q, 16q, 17p, 17q, 18q, and 22q. Overall, the highest frequency of
loss of heterozygosity (LOH) was seen on 4q and 17p, followed by 8p and 16q. Of
the 11 cases studied, 3 cases did not show any of the identical allelic losses
between HCC and CC foci, indicating the biclonal nature. The remaining 8 cases
showed multiple allelic losses shared between both components, strongly
suggestive of a single clonal derivation. Moreover, 4 of the 8 cases showed
additional or divergent allelic losses at more than 1 chromosomal locus only in
HCC and/or CC foci. Thus, this heterogeneity was shown to affect the phenotypic
diversity of the tumor. Summarizing the genetic patterns, combined HCC/CC could
be classified into the following 3 possibilities: (1) collision tumor in which 2
independent neoplastic clones develop at close proximity; (2) single clonal tumor
with homogeneous genetic background in both components--histological diversity is
thus a manifestation of divergent differentiation potential of a single clone;
(3) single clonal process in which genetic heterogeneity in the process of clonal
evolution within the tumor parallels histologic diversity; therefore, the tumor
in this category is mainly composed of mosaics of closely related subclones.
PMID- 11014565
TI - Evaluation of telomerase activity in cutaneous melanocytic proliferations.
AB - Telomerase is an enzyme which synthesizes the telomeres, TTAGGG repeats at the
end of vertebrate chromosomes. Its activity is suppressed in the majority of
somatic cells, whereas it is detectable in most tumor cell lines and human
cancers. Telomerase activity has been evaluated in many tumors for diagnostic
purposes, and an increase thereof has been found with tumor progression. In our
study we used anonisotopic polymerase chain reaction (PCR)-based TRAP (telomeric
repeat amplification protocol) method to quantify the level of telomerase
activity in a series of cutaneous melanocytic lesions. Thirty-three benign nevi,
8 dysplastic nevi, 38 malignant melanomas, and 4 melanoma metastases were
analyzed. Mean relative telomerase activity was low in benign nevi (3.5+/-2.9),
and significantly increased in dysplastic nevi (13.1+/-6.8), malignant melanomas
(49.8+/-29.6), and metastases (121.2+/-11.2). In addition to the evaluation of
telomerase activity as a possible diagnostic tool, its increase with tumor
progression also suggest a prognostic role in cutaneous melanoma.
PMID- 11014566
TI - Correlation between testicular biopsies (prepubertal and postpubertal) and
spermiogram in cryptorchid men.
AB - Twenty-one young men who underwent testicular biopsy and orchidopexy in infancy
consulted owing to infertility and had biopsies again. The first and second
biopsy specimens from these patients were compared by means of a semiquantitative
study of the seminiferous tubules to evaluate the evolution of germ cells and to
correlate these data with spermatozoon numbers. The infant testes showing lesions
were classified into 3 types according to the mean tubular diameter and tubular
fertility index: (1) slight lesions, (2) marked germinal hypoplasia, and (3)
severe germinal hypoplasia. In the adult testes, spermatogenesis was evaluated by
calculating the average numbers of spermatogonia, primary spermatocytes, young
spermatids, and mature spermatids. These testes were classified as (1) normal;
(2) having lesions in the adluminal compartment; (3) having lesions in the basal
compartment; and (4) mixed atrophy. The number of differentiated spermatids was
correlated with the expected number of spermatozoa in the ejaculate by a power
regression curve. The observation of certain histologic lesions in the
seminiferous tubules was assumed to indicate excretory duct obstruction: ectasia,
indented outline of the seminiferous epithelium, intratesticular spermatocele,
apical cytoplasmic vacuolation of Sertoli cells, and mosaic distribution of
testicular lesions. There was a correlation between the prepubertal lesions and
the degree of spermatogenesis in postpubertal biopsy specimens. The evolution of
the 40 testes without regard to their location in infancy (cryptorchid or
scrotal) was as follows. The 14 infant testes with a normal histologic pattern (5
testes) or minor lesions (9 testes) evolved to testes with lesions of the
adluminal compartment (8 testes), mixed atrophy (4 testes), or lesions of the
basal and adluminal compartments (2 testes). The 6 testes with marked germinal
hypoplasia evolved to testes with mixed atrophy. The 20 testes with severe
germinal hypoplasia evolved to testes with mixed atrophy (17 testes), Sertoli
cell-only tubules (2 testes), or lesions in the basal compartment (1 testis). In
the 9 patients with a histologic pattern of obstruction bilaterally (6 men) or
unilaterally (3 men), the expected number of spermatozoa according to the
correlation curve was much higher than the actual number in the spermiogram. This
means that the testes of many azoospermic men produce spermatozoa, and this
finding corroborates the importance of testicular biopsy in infertility studies.
PMID- 11014567
TI - Microsatellite alterations in differentiated-type adenocarcinomas and
precancerous lesions of the stomach with special reference to cellular phenotype.
AB - To elucidate the relationship between genetic alterations and cellular phenotype
of differentiated-type adenocarcinomas and precancerous lesions of the stomach,
we phenotyped 61 gastric tumors consisting of 33 noninvasive lesions and 28
submucosal invasive carcinomas by histochemical and immunohistochemical
techniques, including analysis of mucin expression. We then analyzed loss of
heterozygosity (LOH) at tumor suppressor loci, examined microsatellite
instability (MSI), and compared the results according to cellular phenotype. Of
the 61 gastric tumors studied, 7% (4 of 61) were classified as tumors with a
gastric foveolar epithelial phenotype (foveolar-type), 8% (5 of 61) as tumors
with a complete-type intestinal metaplastic phenotype (CIM-type), and the
remaining 85% (52 of 61) as tumors with an ordinary phenotype (ordinary-type).
Forty-two percent (26 of 61) of the tumors showed LOH on at least 1 chromosomal
arm. Although LOH was rare in foveolar-type tumors, it was present at variable
frequencies at each tumor suppressor loci in tumors with other cellular
phenotypes. p53 overexpression was observed in 0% (0 of 4) of foveolar-type, 48%
(25 of 52) of ordinary-type, and 80% (4 of 5) of CIM-type tumors. With regard to
MSI, all (4 of 4) of the foveolar-type tumors were classified as having high-rate
MSI (MSI-H), whereas all (5 of 5) of the CIM-type tumors were microsatellite
stable (MSS). Of 52 ordinary-type tumors, 19% (10 of 52) were classified as MSI
H, 12% (6 of 52) as low-rate MSI (MSI-L), and 69% (36 of 52) as MSS. The
incidence of MSI-H was found to be significantly higher in foveolar-type tumors
(100%; 4 of 4) than in ordinary-type (19%; 10 of 52) or CIM-type tumors (0%; 0 of
5) (P < .01). An inverse correlation between MSI-H and p53 overexpression was
also noticed (P < .01). Results suggested that each cellular phenotype followed a
different genetic pathway; foveolar-type tumors followed the "mutator" pathway,
characterized by MSI, CIM-type tumors followed the "suppressor" pathway,
characterized by LOH of tumor suppressor loci and p53 overexpression, and
ordinary-type tumors appeared to show mixed genetic alterations of both types.
PMID- 11014568
TI - Frequency of factor V(Leiden) and prothrombin G20210A in placentas and their
relationship with placental lesions.
AB - The most common hereditary hypercoaguable states are factor V(Leiden) (FVL) and
prothrombin mutations (PRO). FVL and PRO present with an incidence of
approximately 5% in a heterogeneous population, and 45% to 63% of the
thrombophilic population. The frequency of these mutations in the fetal
population and their clinical importance is unknown. Fetal side thromboembolic
events (FST) include congenital stroke and renal vein thromboses. In some cases,
FST can be diagnosed by placental histopathology when avascular (infarcted) villi
are present in a patent maternal vascular space. FST can present as placenta
fetal-vascular or fetal-visceral-vascular lesions. Causes include vascular damage
from cord compression or inflammation, but most remain unclear. Potential causes
of FST include FVL and PRO. We describe the incidence of FVL and PRO from a
prospective group of 169 consecutive placentas and in a retrospective group of
archived placentas diagnosed with placental FST. One each of FVL and PRO
heterozygosity was found in the prospective set (< 1% incidence for each). Five
prospective placentas were diagnosed with placental FST, for an incidence of 3%;
all were wild-type for FLV and PRO. Twenty-seven of 65 archived FST cases had
analyzable DNA to find 5 FVL heterozygotes (18.5%); all were wild-type for PRO.
Twenty-one of 65 retrospective archived controls analyzable found 1 case of FVL
heterozygosity (< 5%). We find that the frequency of FVL and PRO may be decreased
in the pregnant population but increased in cases of placental FST. Because
factor V Leiden heterozygosity carries an increased risk for thrombotic
complications, we suggest placental diagnosis of fetal side thromboemboli
warrants clinical evaluation for FVL in infant and potentially the parents.
PMID- 11014569
TI - Pathology residents' use of a Web-based tutorial to improve Gleason grading of
prostate carcinoma on needle biopsies.
AB - Little is known about pathology residents' ability to Gleason grade or their
ability to learn surgical pathology using Internet-based technology. A free Web
based program (available at www.pathology. jhu.edu/prostate) was developed that
consisted of 20 pretutorial images for grading, 24 tutorial images, and the same
20 posttutorial images for Gleason grading. The grading images were selected from
cases that had a consensus Gleason grade from 10 uropathology experts. In 2.5
months, 255 residents visited the website, and 151 (59%) completed it. Of those
who completed the website, their year in training was known in 85 (56%): 1st
year, 25.8%; 2nd year, 20%; 3rd year, 22.3%; 4th year, 14.1%; 5th year, 15.3%;
and 6th year, 2.4%. Eighty percent learned Gleason grading in residency versus
being self-taught, and 66% were male. In a multivariate analysis, higher
pretutorial scores were associated with both their year in training (P = .001)
and their hospital size (P = .003). Improvements in grading posttutorial were not
related to the residents' year in training. Overall, the website significantly
improved grading in 11 of 20 images and had no effect in 9 of 20 images.
Improvements were noted in 1 of 1 Gleason score 4; 2 of 7 Gleason score 5 to 6; 2
of 6 Gleason score 7; and 6 of 6 Gleason score above 7 tumors. In summary, a Web
based tutorial improved Gleason grading accuracy by pathology residents to an
equal extent regardless of their year in training. It is more difficult to teach
residents to grade Gleason scores 5 to 7 tumors, and additional training should
be concentrated in this area.
PMID- 11014570
TI - Anti-CD10 immunoperoxidase staining of paraffin-embedded acute leukemias:
comparison with flow cytometric immunophenotyping.
AB - CD10 is common in B-precursor acute lymphoblastic leukemia (ALL) but is rare in
acute myeloid leukemia (AML). However, until recently, analysis for CD10 has
generally required fresh or frozen tissue. 56C6 is a monoclonal antibody that is
now commercially available for the detection of CD10 in routinely processed
paraffin-embedded tissue. Immunoperoxidase stains for CD10 on paraffin-embedded
bone marrow core biopsy specimens (B5-fixed, decalcified) and marrow aspirate
clots (formalin-fixed) were compared with flow cytometric immunophenotyping for
CD10 on fresh cell suspensions in 20 cases of AML and in 30 cases of ALL. CD10
detection by immunohistochemistry agreed with CD10 by flow cytometry in 98% (49
of 50) of acute leukemias. The results matched in 100% (20 of 20) of AML. Five
percent (1 of 20) of AMLs expressed CD10. Two of the AMLs with monocytoid
differentiation were interpreted as negative for CD10 by flow cytometry, although
these had nonspecific dim immunofluorescence for multiple markers, including
CD10, and these cases were negative by immunohistochemistry. CD10 detection by
immunohistochemistry agreed with CD10 by flow cytometry in 97% (29 of 30) of ALL.
Eighty-four percent (21 of 25) of B-precursor ALL and 40% (2/5) of T-lineage ALL
expressed CD10 by immunohistochemistry. In 1 case of B-precursor ALL, CD10 was
dimly positive in 24% of the blasts by flow cytometry but negative by
immunohistochemistry. We conclude that immunohistochemical staining of paraffin
embedded tissue, either B5- or formalin-fixed, is an effective method for the
detection of CD10 in acute leukemia. This technique is useful in distinguishing
AML from ALL.
PMID- 11014571
TI - Inhibin-alpha CD99, HEA125, PLAP, and chromogranin immunoreactivity in testicular
neoplasms and the androgen insensitivity syndrome.
AB - We investigated 115 testicular and 3 epididymal tumors and 6 cases of the
complete androgen insensitivity syndrome (AIS) for the expression of inhibin
alpha, CD99, HEA125, PLAP, and chromogranin, using monoclonal antibodies and
standard immunhistochemical techniques. Ihibin-alpha was detected in the
neoplastic cells in 27 of 27 primary Leydig cell tumors (LCTs), 1 of 1 metastatic
LCT, 6 of 20 Sertoli cell tumors (SCTs), 4 of 5 juvenile granulosa cell tumors
(GCTs), and 2 of 5 unclassified sex cord-stromal tumors (USCSTs). Except for 2
choriocarcinomas, the choriocarcinomatous component of 1 mixed germ cell tumor,
and a small focus of inhibin-positive syncytiotrophoblast in 1 embryonal
carcinoma, inhibin-a immunoreactivity was not present in the neoplastic cells of
the 38 remaining testicular germ cell tumors; 11 B-cell and 1 T-cell lymphomas; 1
granulocytic sarcoma; and 1 rhabdomyosarcoma of the testis; 1 adenoma of the rete
testis, and 3 adenomatoid tumors of the epididymis. Inhibin-alpha
immunoreactivity was present in the Sertoli cells and Leydig cells in 5
testicular hamartomas and in 1 Sertoli cell adenoma in 6 cases of AIS; both
Sertoli and Leydig cells were also positive in the extranodular testicular
parenchyma present in 2 of these cases. CD99 was detected in 10 of 15 primary
LCTs, 1 of 7 SCTs, 3 of 5 JGCTs, and in 1 of 5 USCSTs but was not found in any
tumor outside the sex cord-stromal category. HEA125 immunostaining was not
detected in sex cord-stromal tumors; however, 3 of 12 seminomas, 3 of 12
embryonal carcinomas, 6 of 8 yolk sac tumors, and 1 of 2 teratomas were HEA125
positive. PLAP was not detected in sex cord-stromal tumors except for 4 of 15
primary LCTs but was present in most germ cell tumors. Chromogranin
immunostaining was present in the sex cord-like element in 1 of 5 USCSTs, 1 of 8
YSTs, 1 of 2 teratomas, and in 1 of 1 rete adenoma, and in normal adjacent rete
testis. In conclusion, although inhibin-alpha and PLAP, and, to a somewhat lesser
extent, CD99 and HEA125 immunostaining are helpful in the differential diagnosis
of certain testicular neoplasms that are difficult to distinguish on morphologic
grounds, chromogranin is far less helpful in this context.
PMID- 11014572
TI - Distribution of keratins in normal endothelial cells and a spectrum of vascular
tumors: implications in tumor diagnosis.
AB - Vascular endothelial cells are specialized mesenchyme-derived epithelial-like
lining cells which are the essential participants in benign and malignant
vascular tumors. Although endothelia in lower animals often express keratins (K),
human endothelia are generally K negative and vimentin-positive. However, K
expression has been noted in some endothelia and in some epithelioid vascular
tumors. In this study, we systematically examined normal human vascular
endothelia and a spectrum of human vascular tumors (n = minimum of 137 tumors
with each marker) for simple epithelial keratin polypeptides of the Moll
catalogue (K7, K8, K18, and K19). Selected vascular tumors were also evaluated
with antibodies to K14 and the monoclonal antibody 34betaE12 that recognizes
several keratins of stratified epithelia. Endothelia of normal veins, venules,
and lymphatics commonly exhibited focal positivity for K7 and K18, whereas K8,
K14, and K19 were not seen in non-neoplastic endothelia with the antibodies used.
Lymphangiomas (6 of 7) and venous hemangiomas (6 of 13) often showed K7-positive
endothelial cells; K18 was detected less commonly, whereas K8 and K19 were not
detected. Epithelioid hemangioendotheliomas (EHEs) showed K7 and K18 expression
in the majority of cases (50% and 100%, respectively), while K8 was seen in 10%
cases and K14 and K19 in none. In contrast, epithelioid angiosarcomas (EAs) were
often positive for K8 and K18 (approximately 50%), whereas they less commonly
showed K7 and only occasionally K19; all tumors were negative for K14 and with
the antibody 34betaE12. Nonepithelioid angiosarcomas (AS) less commonly showed
keratin expression with K7, K8, and K18 being positive in 20% of cases, and K14
and K19 in none of the cases. Epithelial membrane antigen (EMA) was occasionally
detectable in EHE (2/19) but was present in 4 of 16 (25%) EAs and 17 of 48 (35%)
nonepithelioid AS. These findings document the common presence of focal
reactivity for K7 and K18 in subsets of normal endothelia and also the frequent
presence of simple epithelial keratins in malignant vascular tumors, while such
expression is uncommon in nonepithelioid angiosarcomas. K- and EMA-positivity in
neoplastic endothelia needs to be considered in the evaluation of human tumors. K
antibodies such as those specific to K19 or AE1 that do not react with K8 and K18
should be used in the differential diagnosis of epithelioid vascular tumors and
carcinomas.
PMID- 11014573
TI - The expression of fatty acid synthase (FASE) is an early event in the development
and progression of squamous cell carcinoma of the lung.
AB - Correlation of elevated levels of the lipogenic enzyme, fatty acid synthase
(FASE), with advanced stages of some cancers has drawn attention to this enzyme
as a possible marker of poor prognosis. Because recent studies have shown that
cancer cells are dependent on fatty acid synthetic activity and pharmacologic
inhibitors of this enzyme are selectively cytotoxic to cancer cells, expression
of FASE also may provide a potential target for intervention in the neoplastic
process. To determine the potential usefulness of expression of FASE in the
neoplastic process of the lung, we evaluated its pattern of expression
immunohistochemically in archival specimens from 60 human lung specimens with
squamous cell cancer (SCC) and associated "preneoplastic" lesions compared with
its expression in the normal bronchial epithelium of 60 noncancer specimens. The
expression of FASE was significantly higher in SCC associated uninvolved
bronchial epithelium (mean = 0.40+/-0.03, median = 0.38) compared with its
expression in the bronchial epithelium of noncancer specimens (mean = 0.18+/
0.02, median = 0.16) indicating its early expression. We also observed a
statistically significant step-wise increase in FASE expression from SCC
associated uninvolved bronchial epithelium (mean = 0.40+/-0.03, median = 0.38) to
epithelial hyperplasia (0.58+/-0.04, median = 0.57) to SCC (1.53+/-0.06, median =
1.50). The results suggested that expression of FASE is an early event in the
development and progression of SCC of the lung. The inhibition of fatty acid
synthesis by inhibiting enzymatic function with metabolic analogues may be a
useful strategy in the treatment of SCCs. The expression of FASE in early lesions
such as SCC associated uninvolved bronchial epithelium and epithelial hyperplasia
might also provide a potential means for intervention early in the neoplastic
process in the lung or even preventing their malignant transformation to invasive
carcinomas.
PMID- 11014574
TI - Adult rhabdomyoma of the extremity: a case report and review of the literature.
AB - The adult rhabdomyoma is a rare, benign skeletal muscle neoplasm that usually
occurs in the head and neck. A case report of an adult rhabdomyoma arising in the
thigh is presented with a review of the literature. This is the first case of an
extremity adult rhabdomyoma to be reported. It is also the largest at 13
centimeters. Distinction from a highly differentiated rhabdomyosarcoma is
important. Recent chromosomal studies suggest that the adult rhabdomyoma is a
true neoplasm. Total resection is curative but the lesion may recur if
incompletely excised.
PMID- 11014575
TI - Carbohydrate antigen expression in primary tumors, metastatic lesions, and serous
effusions from patients diagnosed with epithelial ovarian carcinoma: evidence of
up-regulated Tn and Sialyl Tn antigen expression in effusions.
AB - The object of this study was the investigation of carbohydrate antigen expression
in malignant epithelial cells and benign mesothelial cells in serous effusions
from patients diagnosed with epithelial ovarian carcinomas. In addition, to
compare antigen expression in carcinoma cells in effusions with those of
corresponding primary tumors and metastatic lesions. Sections from 63 malignant
effusions from ovarian carcinoma patients and 15 reactive effusions were
immunohistochemically stained, using 5 monoclonal antibodies for Lewis(y), Sialyl
Lewis(x), Tn, and Sialyl Tn antigens. Tissue sections (n = 97) from corresponding
primary ovarian carcinomas and metastatic lesions, as well as from 12 malignant
mesotheliomas, were additionally stained using the above panel. Staining for the
4 antigens was seen in carcinoma cells in serous effusions in the majority of
cases (range = 71% to 85%). In contrast, immunoreactivity was detected in
mesothelial cells in only 6% to 23% of the specimens studied (P < .001 for all 5
markers). With the exception of B3 antibody against Lewis(y) antigen, malignant
mesotheliomas stained negative, infrequently showing focal immunoreactivity. An
up-regulation of Tn and Sialyl Tn expression was detected in carcinoma cells in
effusions when compared with both primary tumors (P < .003 and P < .007,
respectively) and metastatic lesions (P < .034 and .041, respectively). Cancer
associated carbohydrate antigens can thus be used as an adjunct in the
differentiation between malignant epithelial and reactive mesothelial cells.
Ovarian carcinoma cells in effusions show up-regulation of Tn and Sialyl Tn,
possibly representing a transient phenotypic alteration facilitating metastasis.
PMID- 11014576
TI - Reduced expression of CD44v3 variant isoform is associated with unfavorable
outcome in non-small cell lung carcinoma.
AB - The expression of CD44 standard form (CD44s) and variant isoforms v3 and v6 was
analyzed in 233 resected non-small cell lung carcinoma (NSCLC) specimens by
immunohistochemistry (IHC), and the mRNA status of CD44v3 and CD44v6 in a cohort
of samples was determined by in situ hybridization (ISH) and further confirmed by
reverse transcriptase polymerase chain reaction (RT-PCR). The expression of
CD44s, CD44v3, and CD44v6 was correlated with clinicopathologic variables and
survival. The expression of CD44v3 and v6 was reduced in 97% and 90% of the
adenocarcinomas and in 86% and 74% of the large cell/anaplastic carcinomas,
respectively, as compared with squamous cell carcinomas, where they were reduced
in 53% and 51% of the cases (P = .0001 and P = .004 for v3 and v6). The
corresponding values for CD44s were 92%, 70%, and 51%, respectively (P = .011).
The reduced CD44s and CD44v6 expression was associated with lymph node metastases
(P = .03 and P = .005, respectively) and the reduced expression of CD44s also
with advanced stage (P = .04). Recurrences during the follow-up were more often
found within the tumors showing reduced expression of CD44v3 (P = .04). Combining
ISH and IHC results showed that CD44v3 and v6 mRNA were not always processed into
protein, suggesting a regulation disturbance posttranscriptionally since
malignant transformation of cells has occurred. In survival analyses, the reduced
expression of CD44s and CD44v3 was associated with a shortened disease-free
survival (P = .04 and P = .01, respectively). In multivariate analysis, CD44v3
retained its independent prognostic value (P = .03). These results emphasize the
value of CD44, and especially the v3 variant isoform in the behavior of NSCLC.
PMID- 11014577
TI - CK7 expression in carcinomas of the Waldeyer's ring area.
AB - Primary carcinomas of the Waldeyer's ring area are typically nonkeratinizing
squamous cell carcinomas (SCC). Their cervical lymph node metastases are not
uncommonly cystic and filled with necrotic tumor cells. Some cysts, however,
contain clear fluid. During the investigation of SCC producing "fluid-filled"
cystic metastases, we evaluated hematoxylin and eosin (H&E) sections of 90
primary SCC for their site of origin. We analyzed the cytokeratin (CK) profile of
primary and metastatic carcinoma with special focus on the expression of CK7, a
putative marker for ductal differentiation. CK7 was expressed in submucosal minor
salivary gland acini and ducts, but not in the squamous surface epithelium of the
Waldeyer's ring. CK7 was expressed in 11 primary SCC (8 base of tongue/3 palatine
tonsil). The CK7-positive SCC were deep-seated, arose from large excretory ducts
of submucosal minor salivary glands, and showed only insignificant surface
involvement. They were characterized by a solid infiltrative growth pattern of
basaloid cells with focal ductal differentiation. Salivary ducts adjacent to the
carcinoma showed extensive intraductal hyperplasia and metaplasia. All CK7
positive carcinomas produced CK7-positive cystic nodal metastases, most of which
contained paucicellular fluid. No solid CK7-positive nodal metastases were
identified. In summary, a subset of carcinomas occurring in the Waldeyer's ring
area appear to arise from large excretory ducts of submucosal minor salivary
glands with only limited surface involvement, express CK7, and produce CK7
positive cystic "fluid-filled" nodal metastases. The histomorphology and
immunophenotype suggest that these carcinomas represent basaloid SCC arising from
excretory ducts of the submucosal minor salivary glands.
PMID- 11014578
TI - Diagnostic effect of an improved preembedding method of prostate needle biopsy
specimens.
AB - The authors compared the influence of a conventional and an optimized submitting
method of prostate core needle biopsy specimens on the frequency of cancer
detected and the pathologic characteristics of the adenocarcinoma bearing biopsy
specimens. The patients included were part of the prostate-specific antigen (PSA)
screening program of Tyrol/Austria. Of the systematic core needle biopsy
specimens from 500 unselected men obtained within 1 year from the Urological
Department, University of Innsbruck, the core biopsy specimens of 250 cases were
submitted conventionally, floating free in formalin-filled containers, whereas
the biopsy specimens of the other 250 cases were stretched and orientated between
2 meshes in tissue cassettes at the time of biopsy before formalin fixation. On
136 cases diagnosed as adenocarcinoma the number and the length of cores as well
as number of the cores involved by cancer and the tumor size were
morphometrically determined. The diagnosis of benign prostatic hyperplasia,
isolated high-grade prostatic intraepithelial neoplasia (PIN), atypical foci
suspicious for cancer, and carcinoma was made in 66%, 5.6%, 4.8%, and 23.6% after
conventional submission and in 61.6%, 6.4%, 1.2%, and 30.8% of the cases after
optimized preembedding respectively. In the adenocarcinoma cases the optimizedly
preembedded material showed higher mean total core length (126.5 mm versus 93.9
mm; P < .0001), a higher mean total tumor length (14.1 mm versus 8.6 mm; P =
.01), and more cores involved by cancer (2.9 versus 2.4; P = .01) compared with
the conventionally worked-up biopsy specimens. Optimized preembedding of core
needle biopsy specimens in tissue cassettes could be quickly and routinely done
by the assistance of the urologists at the time of biopsy. The significant
improvement of the histologic yield of optimizedly preembedded prostatic needle
biopsy specimens led to a higher frequency of cancer diagnosis, a reduction of
cases with atypical foci suspicious for cancer and a significantly lower number
of cases with only 1 core biopsy involved by cancer.
PMID- 11014579
TI - Lipomatous hemangiopericytoma: a fat-containing variant of solitary fibrous
tumor? Clinicopathologic, immunohistochemical, and ultrastructural analysis of a
series in favor of a unifying concept.
AB - The dinicopathologic, immunohistochemical and ultrastructural features of 13
lipomatous hemangiopericytomas are presented. There were 6 male and 7 female
patients whose ages at diagnosis ranged from 27 to 75 years (median 48) all
presenting with a mass of variable duration. The tumor sizes ranged from 1.7 cm
to 19 cm (median 5.5 cm). The locations included the orbit (1), neck (1),
mediastinum (1), epicardium (1), retroperitoneum (3), right iliac fossa (1), and
upper (1) and lower (4) extremity. Histologically, the lesions were composed of a
varying admixture of spindle-shaped to round cells, variably collagenous stroma,
adipose tissue, and branched, often thick-walled, hemangiopericytoma-like
vessels. For 11 tumors, the mitotic activity ranged from 1 to 3 mitoses per 10
high-power fields (HPF). One tumor which contained hypercellular areas showed 13
mitoses per 10 HPF, and another hypercellular lesion showed up to 43 mitoses per
10 HPF, abnormal mitoses, and necrosis. Immunohistochemically, tumor cells were
invariably positive for vimentin and CD99, and mostly for CD34 but negative for
desmin, keratin, CD31, CD117 (c-kit), and inhibin. About half of the tumors
showed reactivity for bcl-2. Occasionally, focal reactivity was also observed for
smooth muscle actin, muscle-specific actin, S100 protein, and epithelial membrane
antigen. Ultrastructural examination of seven cases showed features in keeping
with fibroblastic, myofibroblastic, or pericytic differentiation. Treatment
consisted of simple tumorectomy in 10 cases and wide excision in 3. Follow-up
information on 10 patients (range: 6 to 77 months; median: 18 months) showed no
recurrence. Lipomatous hemangiopericytoma which share the clinical, pathologic,
immunohistochemical, and ultrastructural features of solitary fibrous tumor (SFT)
is likely to represent, in most cases, a fat-containing variant of SFT.
PMID- 11014580
TI - Absence of RBM expression as a marker of intratubular (in situ) germ cell
neoplasia of the testis.
AB - RBM (RNA-binding motif) protein is a marker of male germ cells. This protein is
encoded by the Azoospermia factor region-b (AZF-b) of the human Y chromosome and
is expressed exclusively in the male germ cell line, that is, spermatogonia,
spermatocytes, and round spermatids. The authors analyzed the expression of the
RBM gene in germ cell tumors and in the seminiferous tubules in the vicinity of
these tumors to identify the presence of IGCN. Sections from testicular germ cell
tumors of 21 patients were stained with anti-RBM antibody by using an
immunohistochemical method. Distal tubules showing spermatogenesis were
immunopositive for RBM protein. All of the germ cell tumors studied were
completely immunonegative for RBM. Defined areas of IGCN also showed an absence
of RBM expression. Tubules with spermatocyte-like cells, which were expected to
express RBM, did not express this protein. This result enabled the identification
of tubules as being IGCN. RBM is a novel marker consistently expressed in normal
male germ cells but not in malignant germ cell tumors or IGCN. Thus, the absence
of RBM expression in germ cells provides a new diagnostic tool of preinvasive
malignancy of the testis.
PMID- 11014581
TI - Acute thymic involution in fetuses and neonates with chorioamnionitis.
AB - Chorioamnionitis represents the leading cause of preterm birth and related
pathologic conditions as well as of fetal death and frequently occurs in symptom
free mothers. Recent radiologic findings have indicated that thymus size is
significantly reduced in preterm infants born to mothers with subclinical,
histologically proven chorioamnionitis. However, an accurate morphologic
description of the thymus gland in fetuses and neonates with chorioamnionitis is
lacking, although it is known that infection and other stress processes may cause
lymphocyte depletion in the thymuses of infants and older babies (acute stress
involution). We describe morphologic modifications in the thymus of fetuses with
histologically proven chorioamnionitis and newborn infants with chorioamnionitis
and proven sepsis. The main findings included (1) decreased organ volume (ANOVA,
P < .0024); (2) reduced corticomedullary ratio (P < 10(-6)); (3) significant
changes in the relationship between thymic parenchyma and thymic interstitial
tissue with resulting increased organ complexity (P = .03); (4) severe reduction
of thymocytes; and (5) other degenerative processes such as monocyte/macrophage
infiltration of Hassall's bodies. These results indicate that chorioamnionitis,
with or without sepsis, is associated with significant morphologic modifications
in the thymus. We wish to note that the described thymic pathology is only one
aspect of the fetal systemic inflammatory response syndrome with which
chorioamnionitis is associated.
PMID- 11014582
TI - Peritubular capillaries in chronic renal allograft rejection: a quantitative
ultrastructural study.
AB - Peritubular capillaries (PCs) with a circumferentially multilayered basement
membrane have been suggested as an ultrastructural indicator of chronic renal
allograft rejection (CR). The authors validated this lesion as a marker for CR,
by analyzing its quantitative features, specificity, and sensitivity in 169 renal
biopsy specimens. The mean number of circumferential layers (PCcirc) and the
incidences of the grades (mild: 2 to 4, moderate: 5 to 6, severe: 7 or more
layers) were investigated in biopsy specimens involving CR (CR(Bx), n = 46),
acute rejection (n = 11), normal kidneys (n = 20), psoriatics treated with
cyclosporine (n = 13), renal transplants with chronic cyclosporine toxicity (n =
12), native kidney diseases (NKD, n = 56), and transplant nephrectomies
attributable to CR (Cr(nephr), n = 11). CR was diagnosed with regard to the
clinical features and the presence of intimal fibrosis in 41 biopsy specimens or
transplant glomerulopathy in 35 biopsy specimens (cg; identified only by electron
microscopy in 10 cases). NKD included chronic glomerulonephritis, chronic
tubulointerstitial nephritis, benign nephrosclerosis, thrombotic microangiopathy,
diabetic nephropathy, and renal disease in elderly patients (median age, 72
years). All PCs around glomeruli were sampled (median, 14 profiles per case). PCs
with a moderate/ severe lesion appeared as serrated profiles with a thick, ribbon
like basement membrane layer in semithin plastic sections. The numbers of
circumferentially multilayered PCs were significantly characteristic of CR
(PCcirc in CR(Bx): 2.87+/-1.83 SD; range, 0 to 7.36; P < .001 v other groups). A
severe lesion occurred exclusively in CR (in 12% of the PCs in CR(Bx), and in 38%
in CRnephr). A moderate lesion was observed in 0.6% of the PCs in NKD, 16% in
CR(Bx), and 21% in CRnephr. Three or more PCs with a moderate lesion were
encountered only in CR. A mild lesion was not suggestive of CR at all. In CR(Bx),
27 cases showed a severe lesion or 3 or more PCs with a moderate lesion (cpc;
sensitivity: 59%). Four of the 27 cases lacked cg. The cumulative incidence of
cpc and cg was 85%. In transplants with cyclosporine toxicity, the presence of
cpc verified the coexistence of CR in 7 specimens. In conclusion, cpc is a
specific marker of CR. The incidence of cpc increases as CR progresses. The
lesion may be caused by a low-grade rejection injury to the PCs. Careful analysis
of semithin sections promotes the better sampling of cpc. An ultrastructural
demonstration of cpc and cg defines CR more precisely than does light microscopic
evaluation per se.
PMID- 11014583
TI - Variable expression of keratins and nearly uniform lack of thyroid transcription
factor 1 in thyroid anaplastic carcinoma.
AB - Thyroid anaplastic (undifferentiated) carcinomas (TACs) comprise a
morphologically heterogeneous group of tumors, which can arise in the background
of differentiated papillary or follicular carcinoma. The thyroid epithelial
differentiation varies in these tumors and has not been completely characterized.
In this study, we immunohistochemically analyzed different variants TACs from 35
patients by using antibodies specific to 9 different keratin polypeptides,
epithelial membrane antigen, thyroid transcription factor I (TTF-1), and
thyroglobulin. These tumors were histologically divided into 3 categories:
squamoid-cohesive (SC, 13 tumors), spindle cell sarcomatous (SS, 8 cases) and
intermediate group, including tumors with giant cells and solid epithelioid
components (GC, 18 tumors); 4 tumors had 2 components. The patients ages ranged
from 40 to 89 years, with a mean age in all groups of 70 years. TTF-1 was present
in only 2 of 9 of the SC tumors, and absent in all other TACs, but was present in
entrapped differentiated components. Thyroglobulin was absent in all but 1 case.
A complex keratin (K) pattern of stratified epithelia was typically seen in the
SC tumors with extensive K7, K8, K17, K18, and K19, and variable K13 and K14
expression; EMA was also present. K16 was limited to squamous pearls in 1 tumor,
and K10 was absent. The GC carcinomas typically had K8 and K18, whereas the
expression of K7 was variable and that of K14, K17, and K19 sporadic; EMA was
variably present in half of the cases. The keratins in spindle cell sarcomatous
tumors were usually limited to K7, K8, and K18, often in limited numbers of
cells. EMA was present in 1 case only. These results indicate a complex pattern
of keratins in squamoid and giant cell TACs, similar to papillary carcinoma and
suggesting the possibility of relationship. There was a progressive loss of
epithelial differentiation and keratins in sarcomatoid TACs. Loss of TTF-1 is a
nearly uniform feature of TAC and disallows the use of this marker to pinpoint a
thyroid origin of these tumors.
PMID- 11014584
TI - Reduced 15-lipoxygenase-2 immunostaining in prostate adenocarcinoma: correlation
with grade and expression in high-grade prostatic intraepithelial neoplasia.
AB - Arachidonic acid (AA) metabolites are implicated in the oncogenesis of several
tumors, including prostate cancer. 15-Lipoxygenase-2 (15-LOX-2) is a novel AA
metabolizing enzyme with a limited tissue distribution, which includes prostate,
lung, skin, and cornea. Previous studies have shown that 15-LOX-2 is present in
benign prostate secretory cells and reduced in prostate adenocarcinoma and that
production of the 15-LOX-2 metabolite 15S-hydroxyeicosatetraenoic acid is reduced
in malignant compared with benign prostate. The objective of this study was to
determine the frequency with which 15-LOX-2 immunostaining is reduced in prostate
carcinoma and to correlate reduced expression with tumor differentiation (grade)
and other pathologic parameters in radical prostatectomy specimens. Paraffin
immunoperoxidase with a polyclonal antibody specific for 15-LOX-2 was performed
on tumors and benign portions from 70 cases, and the percentage of tumor
immunostaining for 15-LOX-2 was assessed. Whereas uniform 15-LOX-2 immunostaining
was observed in secretory cells of benign glands, it was markedly reduced or
absent in most adenocarcinomas: 23 of 70 tumors showed completely absent 15-LOX-2
immunostaining, and 45 of 70 cases showed negative immunostaining in more than
50% of the tumor. The extent of reduced 15-LOX-2 immunostaining correlated with
tumor differentiation, with retained expression particularly in Gleason score 5
tumors versus a significant reduction of 15-LOX-2 in higher-grade tumors (mean +/
SD tumor 15-LOX-2 positive: Gleason score 5 = 67%+/-30%, Gleason score 6 = 16%+/
30%, Gleason score 7 = 23%+/-28%, Gleason score > or =8 = 41%+/-46%). In 16 cases
with multifocal tumors or different foci of the same tumor with different grades,
the higher-grade foci had significantly reduced 15-LOX-2 expression compared with
the lower-grade foci. In peripheral zone tumors without complete loss of 15-LOX-2
expression, there was a significant inverse relationship between 15-LOX-2
immunostaining and tumor volume. There was not a significant correlation between
15-LOX-2 immunostaining and serum PSA or pathologic stage. In a subset of 27
cases, 15-LOX-2 expression in high-grade prostatic intraepithelial neoplasia
(HGPIN) glands was significantly reduced compared with benign glands. These data
show that in contrast to the uniform expression of 15-LOX-2 in differentiated
secretory cells of benign prostate, reduced 15-LOX-2 is a common alteration in
prostate carcinoma, and this correlates with tumor cell differentiation. That
reduced expression is seen in HGPIN suggests that this may be an early alteration
in carcinoma development.
PMID- 11014585
TI - Efficacy of restaining prostate needle biopsies with high-molecular weight
cytokeratin.
AB - Prostate tissue and lesions obtained by needle biopsy may be scant and not
survive cutting into the block; this study examined the efficacy of destaining
hematoxylin and eosin-stained sections and restaining the slides using
immunohistochemistry with high-molecular weight cytokeratin (high-molecular
weight cytokeratin). We identified 105 prostate needle biopsies referred to Johns
Hopkins Hospital in an 18-month period (January 1997-June 1998) that had been
destained and restained for high molecular weight cytokeratin. The slides were
reviewed for the Johns Hopkins Hospital diagnosis (benign, malignant, or
equivocal), which had factored in the immunohistochemistry results, and for
immunohistochemistry staining quality (optimal, suboptimal, stain failed, or
lesion fell off). We obtained data on 96 cases from the referring institutions
about the fixative and glass slides used for processing the needle biopsy. In 58%
of cases, destaining and restaining with high-molecular weight cytokeratin
allowed a definitive benign or malignant diagnosis to be made; in 79% of these
cases, the staining was optimal. In only 13% of cases the diagnosis remained
equivocal; of these, the stain worked optimally in only 36%. In 19% of cases, the
stain failed. In 9% of cases, the lesion fell off; in all 7 cases with available
data the tissue had been cut on non-charged slides. All but 3 cases were received
in 10% neutral buffered formalin. There was no correlation between the use of
charged (plus or lysine coated) or non-charged slides and the staining quality.
Furthermore, in 12 instances, we received more than 1 specimen from the same
referring institution, and in 6 of these instances there was variable staining in
the different cases from the same institution. Destaining hematoxylin and eosin
stained slides and restaining for high-molecular weight cytokeratin is a useful
technique that in the majority of cases enables a definitive diagnosis to be
made. Tissue may survive the procedure better if originally cut on charged
slides, but staining quality is no different for charged or non-charged slides.
PMID- 11014586
TI - Massive localized lymphedema: additional locations and association with
hypothyroidism.
AB - We report the second series of a new entity called "massive localized lymphedema
in morbidly obese patients" (MLL), recently described in medical literature. Our
6 cases present additional locations as well as an association with
hypothyroidism. Huge masses, of longstanding duration ranging from 9 months to 8
years, afflicted the thigh, popliteal fossa, scrotum, suprapubic and inguinal
region, and abdomen of morbidly obese adults. Although clinical impressions were
generally of a benign process, including lipoma and recurrent cellulitis, the
possibility of a malignant neoplasm could not be eliminated. Poorly defined and
non-encapsulated, these skin and subcutaneous lesions were most remarkable for
their sheer size, measuring 50.6 cm in mean diameter (range, 38-75 cm) and
weighing a mean of 6764.5 g (range, 2,060-12,000 g) The overlying skin exhibited
the induration and peau d'orange characteristic of chronic lymphedema. Grossly
and histologically, a prominent marbled appearance, rendered by fibrous bands
intersecting lobules of adipose tissue, simulated sclerosing well differentiated
liposarcoma. However, the absence of atypical stromal cells, atypical adipocytes,
and lipoblasts precluded the diagnosis of well differentiated liposarcoma.
Instead, reactive features, encompassing lymphatic vascular ectasia, mononuclear
cell infiltrates, fibrosis, and edema between the collagen fibers, as well as
ischemic changes including infarction and fat necrosis, established the diagnosis
of MLL. Although the pathogenesis of MLL may be as simple as obstruction of
efferent lymphatic flow by a massive abdominal pannus and/or prior surgery, the
presence of hypothyroidism in 2 of our patients suggests an alternative
pathogenesis. Recognition of this entity by both clinicians and pathologists
should avert a misdiagnosis as a low-grade liposarcoma.
PMID- 11014587
TI - A variant form of Churg-Strauss syndrome: initial temporal non-giant cell
arteritis followed by asthma--is this a distinct clinicopathologic entity?
AB - The clinical manifestations of the classical vasculitis syndromes are
extraordinarily heterogenous with considerable overlap among them. Recently,
several cases of unusual presentation of the vasculitis syndromes have been
reported. We describe a patient who initially manifested with temporal arteritis
and Raynaud's phenomenon and subsequently developed bronchial asthma, ie, a case
of an atypical form of Churg-Strauss syndrome (allergic angiitis and
granulomatosis) and discuss whether this case is a distinct clinicopathological
entity.
PMID- 11014588
TI - CD138-positive and Kaposi's sarcoma-associated herpesvirus (KSHV)-negative B-cell
lymphoma with serosal spreading of the body cavity and lymphadenopathy: an
autopsy case.
AB - CD138-positive and Kaposi's sarcoma-associated herpes virus (KSHV)-negative B
cell lymphoma with serosal spreading of the body cavity and lymphadenopathy is
presented. Our lymphoma cells showed pleomorphic morphology and a clonal
immunoglobulin gene rearrangement. Immunophenotypically, they lacked B- and T
cell-associated antigens but expressed strong membranous CD138 antigen along the
serosa. Although our case was not conventional primary effusion lymphoma (PEL)
because of the absence of KSHV and the presence of lymphadenopathy, its unique
phenotype and serosal spreading were consistent with those of PEL. Our case
suggests that, irrespective of KSHV infection, some pleomorphic B cell lymphomas
with membranous CD138 expression show a peculiar serosal spreading.
PMID- 11014589
TI - Adhesion molecule detection in a case of early cerebral malaria:
immunohistochemical and electron microscopic findings.
AB - A case of early cerebral malaria caused by Plasmodium falciparum was studied. P
selectin glycoprotein ligand 1 (PL1) was detected along the inner surface of the
infected red blood cells (IRBCs), which ordinarily are not positive for PL1
immunohistochemically, suggesting PL1 being the product of parasite. The electron
microscopic finding showed granular deposits in the corresponding lesion,
consistent with PL1 deposition, in the IRBCs firmly attached to the endothelium
of small cerebral vessels. Most of the IRBCs were round shaped as though they
lost their capacity to change shape. The therapeutic strategy was expected
against adhesion molecules such as PL1 and for maintaining or restoring the
metamorphic capacity of IRBCs.
PMID- 11014590
TI - Atypical immature metaplastic-like proliferation of the cervix.
PMID- 11014591
TI - The adhesion molecule expression pattern of basal cell carcinoma cells should be
compared with outer root sheath cells of hair follicle and not with stratum
basale of skin.
PMID- 11014592
TI - DipoCoup: A versatile program for 3D-structure homology comparison based on
residual dipolar couplings and pseudocontact shifts.
AB - A program, DipoCoup, is presented that allows to search the protein data bank for
proteins which have a three dimensional fold that is at least partially
homologous to a protein under investigation. The three dimensional homology
search uses secondary structure alignment based on chemical shifts and dipolar
couplings or pseudocontact shifts for the three dimensional orientation of
secondary structure elements. Moreover, the program offers additional tools for
handling and analyzing dipolar couplings.
PMID- 11014593
TI - The auto-orientation in high magnetic fields of oxidized cytochrome b562 as
source of constraints for solution structure determination.
AB - 15N-1H 1J couplings were measured at 500 MHz and 800 MHz for 15N enriched
oxidized cytochrome b562 from E. coli. The magnetic field dependence of 70 1J
values, which could be measured without signal overlap, shows that there is a
molecular magnetic anisotropy which provides partial molecular orientation in the
magnetic field and, consequently, residual dipolar couplings (rdc). The rdc were
used as further constraints to improve the existing structure [Arnesano et al.
(1999) Biochemistry, 38, 8657-8670] with a protocol which uses the rhombic
anisotropy [Banci et al. (1998) J. Am. Ctherz. Soc., 120, 12903-12909]. The
overall large molecular magnetic anisotropy has been found to be determined by
both the low spin iron (III) and the four helix bundle structure magnetic
susceptibility anisotropy contributions.
PMID- 11014594
TI - NMR detection of side chain-side chain hydrogen bonding interactions in 13C/15N
labeled proteins.
AB - We describe the direct observation of side chain-side chain hydrogen bonding
interactions in proteins with sensitivity-enhanced NMR spectroscopy.
Specifically, the remote correlation between the guanidinium nitrogen 15Nepsilon
of arginine 71, which serves as the hydrogen donor, and the acceptor carboxylate
carbon 13CO2gamma of aspartate 100 in a 12 kDa protein, human FKBP12, is detected
via the trans-hydrogen bond 3h JNepsilonCO2gamma coupling by employing a novel
HNCO-type experiment, soft CPD-HNCO. The 3h JNepsilonCO2gamma coupling constant
appears to be even smaller than the average value of backbone 3h JNC' couplings,
consistent with more extensive local dynamics in protein side chains. The
identification of trans-hydrogen bond J-couplings between protein side chains
should provide useful markers for monitoring hydrogen bonding interactions that
contribute to the stability of protein folds, to alignments within enzyme active
sites and to recognition events at macromolecular interfaces.
PMID- 11014595
TI - Amino acid-specific isotopic labeling and active site NMR studies of iron(II)-
and iron(III)-superoxide dismutase from Escherichia coli.
AB - We have developed and employed multiple amino acid-specific isotopic labeling
schemes to obtain definitive assignments for active site 1H NMR resonances of
iron(II)- and iron(III)-superoxide dismutase (Fe(II)SOD and Fe(III)SOD) from
Escherichia coli. Despite the severe relaxivity of high-spin Fe(III), we have
been able to assign resonances to ligand His' delta1 protons near 100 ppm, and
beta and alpha protons collectively between 20 and 50 ppm, in Fe(III)SOD. In the
reduced state, we have assigned all but 7 ligand protons, in most cases residue
specifically. A pair of previously unreported broad resonances at 25.9 and 22.1
ppm has been conclusively assigned to the beta protons of Asp 156, superseding
earlier assignments (Ming et al. (1994) Inorg. Chem., 33, 83-87). We have
exploited higher temperatures to resolve previously unobserved ortho-like ligand
His proton resonances, and specific isotopic labeling to distinguish between the
possibilities of 82 and epsilon1 protons. These are the closest protein protons
to Fe(II) and therefore they have the broadest (approximately 4,000 Hz) and most
difficult to detect resonances. Our assignments permit interpretation of
temperature dependences of chemical shifts, pH dependences and H/D exchange rates
in terms of a hydrogen bond network and the Fe(II) electronic state.
Interestingly, Fe(II)SOD's axial His ligand chemical shifts are similar to those
of the axial His ligand of Rhodopseudomonas palustris cytochrome c' (Bertini et
al. (1988) Inorg. Chem., 37, 4814-4821 ) suggesting that Fe(II)SOD's equatorial
His2Asp- ligation is able to reproduce some of the electronic, and thus possibly
chemical, properties of heme coordination for Fe2+.
PMID- 11014596
TI - Radiation damping compensation of selective pulses in water-protein exchange
spectroscopy.
AB - The observation of nuclear Overhauser effects (NOEs) between bound water and
biological macromolecules such as proteins and nucleic acids can be improved by
inverting the water resonance selectively while compensating for radiation
damping effects. The efficiency of inversion, the offset profiles, and the
appearance of 2D NOE-NOESY spectra can be improved in comparison with earlier
methods.
PMID- 11014597
TI - Bridging the gap: A set of selective 1H-15N-correlations to link sequential
neighbors of prolines.
AB - Triple-resonance experiments are standard in the assignment of protein spectra.
Conventional assignment strategies use 1H-15N-correlations as a starting point
and therefore have problems when proline appears in the amino acid sequence,
which lacks a signal in these correlations. Here we present a set of amino acid
selective pulse sequences which provide the information to link the amino acid on
either side of proline residues and thus complete the sequential assignment. The
experiments yield amino acid type selective 1H-15N-correlations which contain
signals from the amino protons of the residues either preceding or following
proline in the amino acid sequence. These protons are correlated with their own
nitrogen or with that of the proline. The new experiments are recorded as two
dimensional experiments and their performance is demonstrated by application to a
115-residue protein domain.
PMID- 11014598
TI - Expression of deuterium-isotope-labelled protein in the yeast pichia pastoris for
NMR studies.
AB - Deuterium isotope labelling is important for NMR studies of large proteins and
complexes. Many eukaryotic proteins are difficult to express in bacteria, but can
be efficiently produced in the methylotrophic yeast Pichia pastoris. In order to
facilitate NMR studies of the malaria parasite merozoite surface protein-1 (MSP1)
complex and its interactions with antibodies, we have investigated production of
the MSP1-19 protein in P. pastoris grown in deuterated media. The resulting
deuteration patterns were analyzed by NMR and mass spectrometry. We have compared
growth characteristics and levels of heterologous protein expression in cells
adapted to growth in deuterated media (95% D2O), compared with expression in non
adapted cells. We have also compared the relative deuteration levels and the
distribution pattern of residual protiation in protein from cells grown either in
95% D2O medium with protiated methanol as carbon source, or in 95% D2O medium
containing deuterated methanol. A high level of uniform Calpha deuteration was
demonstrated, and the consequent reduction of backbone amide signal linewidths in
[1H/15N]-correlation experiments was measured. Residual protiation at different
positions in various amino acid residues. including the distribution of methyl
isotopomers, was also investigated. The deuteration procedures examined here
should facilitate economical expression of 2H/13C/15N-labelled protein samples
for NMR studies of the structure and interactions of large proteins and protein
complexes.
PMID- 11014599
TI - 1H, 13C, and 15N backbone assignments of the ligand binding domain of TGFbeta
type II receptor.
PMID- 11014600
TI - NMR backbone assignments of the cold-regulated RNA-binding protein, rbpA1, in the
cyanobacterium, anabaena variabilis M3.
PMID- 11014601
TI - Sequence-specific NMR resonance assignments of the backbone atoms for the
olfactory marker protein, OMP.
PMID- 11014602
TI - Assignment of 1H, 13C and 15N signals of bovine adrenodoxin.
PMID- 11014603
TI - Backbone 1H, 13C, and 15N resonance assignments of the anti-dansyl antibody Fv
fragment.
PMID- 11014604
TI - Backbone 1H, 15N, and 13C resonance assignments of inhibitor-2 -- a protein
inhibitor of protein phosphatase-1.
PMID- 11014605
TI - Isoflurane anaesthetic depth in goats monitored using the bispectral index of the
electroencephalogram.
AB - The bispectral index (BIS) of the electroencephalogram has recently been used to
monitor the depth of anaesthesia in humans. The BIS is a dimensionless number
that varies between 0 and 100. We hypothesized that the BIS could also be used to
monitor depth of isoflurane anaesthesia in goats. Needle electrodes were placed
over the frontal region of the scalp of goats and 5%, isoflurane was administered
via a mask. The BIS number was determined at clinically relevant end-points. The
BIS number did not change when the animals became recumbent (95 +/- 5 to 94 +/-
7, n = 15), but decreased to 65 +/- 13 and 64 +/- 15 when the corneal reflex and
withdrawal response to a noxious stimulus, respectively, were lost (p < 0.001, n
= 12). Direct laryngoscopy and intubation increased the BIS (56 +/- 7 to 83 +/-
11; p < 0.05, n = 10), as did a noxious pinch to the dew-claw (57 +/- 9; to 76 +/
9; p < 0.05, n = 10). The spectral edge (frequency below which 95% of the total
power resided) paralleled the change in BIS. We conclude that the depth of
isoflurane anaesthesia in goats can be monitored using the BIS, although further
work is needed to determine its sensitivity and specificity.
PMID- 11014606
TI - Aeromonas hydrophila isolated from wild freshwater fish in Croatia.
AB - Aeromonas hydrophila was recovered from fish living in lake Vrana on the Croatian
island of Cres. The occurrence of the bacterium in the fish was assessed and
related to gross signs of disease and findings at necropsy as a potential health
hazard for fish. Isolated bacteria were subjected to morphological,
physiological, biochemical and antibiotic susceptibility tests. A total of 26 A.
hydrophila isolates were obtained. There was a clear seasonality, as no isolates
were recovered in the summer months. Most of the isolates were sensitive to all
the antimicrobials used in the study except novobiocin and penicillin G. Affected
fish manifested haemorrhages over the skin, in the liver, kidney and swim
bladder, spleen infarcts, fatty liver, ascitic fluid and swollen haemopoietic
tissues. A. hydrophila does not appear to pose a major threat for the fish in the
lake at present but under unfavourable and stressful conditions it could
seriously compromise fish health.
PMID- 11014607
TI - In vitro metabolism of fumonisin B1 by ruminal microflora.
AB - Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium moniliforme and F.
proliferatum. Little is known of its metabolic fate after oral ingestion in
ruminants, but these animals are reported to be tolerant towards FB1. The
metabolism of this mycotoxin was evaluated following incubation (1 microg/ml) in
ruminal fluid for up to 72 h, in the presence or absence of alfalfa as a
substrate for microbial growth, using a model rumen (sealed flask, anaerobic
conditions, exclusion of light, gentle agitation, 39 degrees C). The decrease in
FB1 concentration and the production of short-chain fatty acids were determined.
FB1 had no effect on SCFA production. After 72 h incubation, FB1 depletion was
12% and 18% in samples with and without alfalfa, respectively. No hydrolysed
metabolites (aminopolyols or aminopentol) were detected. These results indicate
that FB1 is poorly metabolized in the rumen and suggest that such metabolism is
not the cause of the tolerance to this toxin displayed by ruminants.
PMID- 11014608
TI - Efficacy of copper oxide needles for the control of nematode parasites in dairy
goats.
AB - The spread of benzimidazole-resistant nematodes in dairy goat farms is of a great
concern as probably more than 70% of the flocks are involved. As there are very
few other anthelmintic options during the lactating period, we have evaluated the
efficacy of copper oxide needles (CON, Copinox, Bayer, UK) in both experimental
and natural infections in goats. The curative effect of CON (2-4 g) on existing
worm burdens was assessed in goats experimentally infected with Teladorsagia
circumcincta, Haemonchus contortus and Trichostrongyus colubriformis, compared to
controls. The preventive effect of CON (4 g) on worm establishment was monitored
for 2 months in animals experimentally infected with H. contortus and for 3
months in naturally infected animals on a farm exhibiting predominant infections
with T. circumcincta and Oesophagostomum venulosum. In both experimental and
natural conditions, the efficacy of CON was nil against Teladorsagia,
Trichostrongylus and Oesophagostomum infections. In contrast, the efficacy of CON
against Haemonchus was clearly established in reducing the worm burden (75%) as
well as in lowering the egg output (37-95%) in relation to the establishment of
new infections over several weeks. Copper oxide needles may represent an
alternative to conventional anthelmintics in the control of Haemonchus infection
in some goat farms.
PMID- 11014609
TI - Characterization of an Indian bluetongue virus isolate by RT-PCR and restriction
enzyme analysis of the VP-7 gene sequence.
AB - The reverse transcription-polymerase chain reaction (RT-PCR) was standardized to
amplify the VP-7 gene sequences of an Indian isolate of bluetongue virus serotype
23. Using two different sets of primers, a sequence of 1156 bp comprising the
complete coding sequence of the VP-7 gene and its 770 bp internal sequence were
amplified. The sensitivity of RT-PCR, using these two sets of primers
individually was 40 pg and 4 pg, with the external and internal primers,
respectively, whereas the nested PCR was 100-fold more sensitive than the single
PCR with the external primers. Further, by restriction enzyme digestion of the
1156 bp amplicon, using CfoI, PstI and TaqI enzymes, the Indian isolate was found
to be genetically different from isolates from the United States and Australia.
RT-PCR and restriction enzyme digestion were applied to detect virus directly in
blood samples taken from sheep suspected of bluetongue virus infection.
PMID- 11014610
TI - Molecular typing of a BHV-4 (bovine herpesvirus 4) field isolate.
AB - A new BHV-4 (bovine herpesvirus 4) isolated from a case of bovine interdigital
dermatitis was characterized by PCR and restriction enzyme analysis. To determine
whether the new isolate (PR/1) belonged to BHV-4, DNA from infected cells was
specifically amplified by PCR. We used a set of primers spanning a large 2.571 kb
conserved region of the BHV-4 genome, including the 3' end of ORF1 (homologous to
the EBV BVRF1 gene), ORF2 (homologous to the EBV BXRF1 gene), ORF3 (TK gene) and
ORF4 (gH gene) 5' end, respectively. The identity of the amplified product was
confirmed by HindIII restriction enzyme digestion and Southern hybridization. No
product was observed from the DNA of other bovine herpesviruses tested. The
restriction patterns of the PR/ 1 genome compared to DN 599, MOVAR 33/63 and LVR
BHV-4 reference strains showed two kinds of differences, either related or not
related to the prDNA (polyrepetitive DNA). Taken together, these data show that
PR/ 1 is a new BHV-4. We would consider that the present report provides a scheme
of work for diagnosis and typing of BHV-4 isolates.
PMID- 11014611
TI - Genomic and pathogenic studies on a glycoprotein E variant field isolate of
bovine herpesvirus 1.
AB - Glycoprotein E-negative (gE-) laboratory strains of bovine herpesvirus 1 (BHV-1)
were recently introduced as novel marker vaccines, allowing serological
discrimination between vaccinated and naturally infected animals on the basis of
lack or presence of antibodies against gE epitopes. The applicability pf this
approach is based on the genetic stability of the gE. However, mutant field
variants of BHV-1 with a variable response in anti-gE ELISA have been isolated.
The molecular characterization of a gE variant field isolate (Salwa strain) is
presented here. By comparing the gE nucleotide and amino acid sequences of the
Salwa strain with those of the wild strain Jura, ten mutated bases were found in
the gE strain of Salwa, six of which alter the amino acid sequence, leading to
changes in five amino acids. Both strains caused respiratory disease in
experimentally infected calves, but Salwa generated slightly milder signs. Both
viruses were excreted in nasal and ocular discharges, and were reactivated by
dexamethasone treatment. In conclusion, the rather close similarities observed in
the gE gene structure and pathogenicity features of the gE mutant and of the wild
strain of BHV-1 confirm the genetic stability of gE. The findings indicate that
the Salwa isolate is virulent, but less virulent than wild strains. Our data
support the use of gE-negative marker vaccines in eradication programmes.
PMID- 11014612
TI - Behavioral despair in mice after prenatal stress.
AB - Maternal stress during pregnancy produced behavioral alterations in both sexes
with regard to sexual behavior, aggressive, maternal, lateralization and
depression. In the present paper, sex differences for depression in mice was
studied. No sex differences between female and male mice groups were observed
either in swimming-induced immobility or in the open-field test (ambulation,
rearing and boluses). Prenatal stress produced: 1) an increase of immobility time
in female mice for swimming-induced immobility, but not in male mice; 2) an
increase of ambulation in female mice for open-field test, but not in male mice;
3) there were no significant differences in rearing and boluses between stress
and control groups either for female or male mice. Prenatal stress increases the
risk of depression and locomotor activity in adult female mice.
PMID- 11014613
TI - Prolactin and cyclosporine modulate adenosine transporters and adenosine A1
receptors in the rat brain.
AB - The existence of adenosine A1 receptors and adenosine transporters in the central
nervous system has been well demonstrated, although their possible modulation by
hormones and/or exogenous drugs is poorly understood. To further analyze these
modulatory mechanisms, the effects of prolactin and cyclosporine (CyA) on
adenosine A1 receptors and transporters were analyzed in the central nervous
system. For this purpose the number and affinity of adenosine A1 receptors were
measured using the specific antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX)
and the transporters with the high affinity ligand nitrobenzylthioinosine (NBTI).
This procedure was carried out in hyperprolactinemic and control male rats
treated with CyA or its vehicle for 8 days. As expected, pituitary grafting
increased plasma prolactin levels (p<0.01). CyA treatment reduced but did not
normalize (p<0.05) this parameter in hyperprolactinemic rats and did not modify
circulating prolactin in control animals. Both hyperprolactinemia and CyA
treatment reduced the number of adenosine transporters by 70% and by 40% the
number of A1 receptors. The Kd for transporters was also reduced in all
experimental groups. Hyperprolactinemia increased the affinity of A1 receptors
(p<0.01) and CyA treatment did not further modify this parameter. These data
demonstrated that prolactin and CyA influence adenosine transporters and A1
receptors at the central nervous system and suggest the existence of an
interaction between prolactin and CyA may be operating to modulate these
processes.
PMID- 11014614
TI - Effects of IGF-I treatment on osteopenia in rats with advanced liver cirrhosis.
AB - IGF-I is an anabolic hormone which has been reported to increase bone formation
in several conditions of undernutrition. Advanced liver cirrhosis is associated
with osteopenia and also with low serum levels of IGF-I. Previous results showed
that low doses of IGF-I increase osteoblastic activity and decrease bone
reabsorption in early liver cirrhosis. The aim of this study was to evaluate
whether IGF-I-treatment also induces beneficial effect on osteopenia associated
with advanced cirrhosis. Rats with ascitic cirrhosis were divided into two
groups: group CI (n=10) which received saline and group CI+IGF (n=10) which were
treated with IGF-I (2 microg/100 g bw x day, sc, during 21 days). Healthy
controls which received saline were studied in parallel (CO n=10). On the 22nd
day, the animals were sacrificed, and bone parameters were analyzed in femur.
Posterior-anterior diameter was similar in all groups. No significant differences
were observed in bone content of calcium, total proteins, collagen and
hydroxyapatite in cirrhotic rats as compared with controls. However, CI rats
showed significant reductions in total bone density (-13.5%, p<0.001) assessed by
densitometry and radiological study. In CI+IGF rat bone density (assessed by
densitometry) improved significantly as compared with CI animals. In summary,
osteopenia characterized by loss of bone mass and preserved bone composition was
found in rats with advanced cirrhosis induced by CCl4 and phenobarbital in
drinking water. This bone disorder is partially restored by treatment with low
doses of IGF-I during only three weeks. Thus, IGF-I could be considered as a
possible therapy for osteopenia associated with advanced liver cirrhosis.
PMID- 11014615
TI - Retinoid X receptor mRNA expression in human pituitary gland.
AB - Retinoic acid is involved in important physiological processes such as the
regulation of growth and differentiation of several tissues, including the
pituitary gland. These biological effects are mediated by their binding to two
specific intracellular receptors termed retinoic acid and retinoid X receptors,
RARs, RXR, respectively). RAR or RXR mRNA expression has been demonstrated in
several tissues, but little information is available about its presence in the
human pituitary gland. In this report, we demonstrate alphaRXR mRNA expression
using the reverse transcription coupled to polymerase chain reaction (RT-PCR) in
the human pituitary gland. These results suggest the possibility that RXR may
regulate the human pituitary gene expression and hormone secretion.
PMID- 11014616
TI - Growth hormone response to long-term GH-RH administration in lambs.
AB - The pattern of long-term GHRH administration capable of stimulating GH release
without depleting pituitary GH content has been investigated using two
experimental approaches. In experiment 1, recently weaned male lambs were treated
for 3 weeks as follows: Group A) control; B) subcutaneous (sc) continuous
infusion of GHRH (1200 mg/day) using a slow release pellet; C) the same as B plus
1 daily sc injection of long acting somatostatin (SS) (octreotide, 20 mg) ; D) 3
daily sc GHRH (250 mg) injections ; E) 2 daily sc injections of GHRH (250 mg) and
2 of natural SS (250 mg). In experiment 2, recently weaned male lambs were
continuously GHRH-treated using sc osmotic minipumps (900 mg/day) alone or
combined with a daily sc injection of octreotide (20 mg) for 4 weeks. Basal
plasma GH levels were increased after chronic pulsatile GHRH treatment but not
after any kind of continuous GHRH administration. This increment was maintained
during the 3 weeks of experimentation and appeared accompanied by a pituitary GH
content similar to controls. A marked GH response to the iv GHRH challenge was
observed in controls and in lambs receiving both types of continuous sc GHRH
infusions, whereas pulsatile sc GHRH-treated animals did not respond to the iv
GHRH challenge in the first and second weeks of the study but did so in the third
week of treatment. These data demonstrate that long-term pulsatile GHRH
administration is capable of stimulating GH release in growing male lambs,
without producing pituitary desensitization.
PMID- 11014617
TI - Nutrient toxicity in pancreatic beta-cell dysfunction.
AB - Nutrients, such as glucose and fatty acids, have a dual effect on pancreatic beta
cell function. Acute administration of high glucose concentrations to pancreatic
beta-cells stimulates insulin secretion. In addition, short term exposure of this
cell type to dietary fatty acids potentiates glucose-induced insulin release. On
the other hand, long-term exposure to these nutrients causes impaired insulin
secretion, characterized by elevated exocytosis at low concentrations of glucose
and no response when glucose increases in the extracellular medium. In addition,
other phenotypic changes are observed in these conditions. One major step in
linking these phenotypic changes to the diabetic pathology has been the
recognition of both glucose and fatty acids as key modulators of beta-cell gene
expression. This could explain the adaptative response of the cell to sustained
nutrient concentration. Once this phase is exhausted, the beta-cell becomes
progressively unresponsive to glucose and this alteration is accompanied by the
irreversible induction of apoptotic programs. The aim of this review is to
present actual data concerning the development of the toxicity to the main
nutrients glucose and fatty acids in the pancreatic beta-cell and to find a
possible link to the development of type 2 diabetes.
PMID- 11014618
TI - Energy expenditure during leisure time and body mass index in Spain.
PMID- 11014619
TI - Management of cytomegalovirus retinitis in AIDS.
PMID- 11014620
TI - Clinical manifestations and molecular epidemiology of late recurrent candidemia,
and implications for management.
AB - The aim of this study was to define the epidemiology and clinical manifestations
of late recurrent candidemia. For this purpose, late recurrent candidemia was
defined as an episode of candidemia occurring at least 1 month after the apparent
complete resolution of an infectious episode caused by the same Candida sp. A
total of five patients with recurrent candidemia were investigated. For all
patients, isolates from the initial and recurrent episodes of candidemia were
available for in vitro susceptibility testing and genetic characterization by DNA
based techniques. The results revealed the following salient features: prolonged
duration between the initial and recurrent episodes (range, 1-8 months);
recurrence of candidemia despite anti-fungal therapy; importance of retained
intravascular catheters, neutropenia, and corticosteroids as factors predisposing
to recurrence; high morbidity and mortality; no emergence of antifungal drug
resistance between the initial and recurrent episodes; and relapse of infection
due to the original infecting strain, rather than reinfection with a new strain.
These findings raise several issues about the management and follow-up of
patients with candidemia, which require assessment in future studies.
PMID- 11014621
TI - Determinants for the development of oropharyngeal colonization or infection by
fluconazole-resistant Candida strains in HIV-infected patients.
AB - A point prevalence study to document oral yeast carriage was undertaken. Risk
factors for the development of oropharyngeal colonization or infection by
fluconazole-resistant Candida strains in HIV-infected patients were investigated
with a case-control design. Cases included all patients with fluconazole
resistant strains (MIC> or =64 microg/ml), and controls were those with
susceptible (MIC< or =8 microg/ml) or susceptible-dependent-upon-dose (MIC 16-32
microg/ml) strains. One hundred sixty-eight Candida strains were isolated from
153 (88%) patients, 28 (16%) of whom had oropharyngeal candidiasis. Overall, 19
(12%) of the patients harbored at least one resistant organism (MIC > or = 64
microg/ml). Among patients with resistant strains, tuberculosis (P<0.001),
esophageal candidiasis (P = 0.001), clinical thrush (P<0.001), and a CD4 + cell
count < 200/mm3 (P = 0.03) were more frequent. These patients had also been
treated more commonly with antituberculous drugs (adjusted odds ratio [OR] 6.13;
95% confidence interval [CI] 2.11-17.80), ciprofloxacin (OR 6.0; 95% CI 1.23
29.26), fluconazole (OR 4.59; 95% CI 1.55-13.52), and steroids (OR 4.13; 95% CI
1.11-15.39). Multivariate analysis showed that the determinants for fluconazole
resistance were therapy with antituberculous drugs (OR 3.61; 95% CI 1.08-12.07;
P=0.03) and one of the following: previous tuberculosis (OR 3.53; 95% CI 1.08
14.57; P=0.03) or fluconazole exposure (OR 3.41; 95% CI 1.10-10.54). Findings
from this study indicate that treatment with antituberculous drugs, previous
tuberculosis, and fluconazole exposure are the strongest determinants for
development of oropharyngeal colonization or infection by fluconazole-resistant
Candida strains in HIV-infected patients.
PMID- 11014622
TI - Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care
hospital.
AB - In a retrospective study conducted in an Italian tertiary care hospital, the
incidence of nosocomial candidemia was evaluated together with causative
pathogens, treatment, and risk factors for death. Over a 6-year period (1992
1997), a total of 189 episodes of candidemia occurred in 189 patients (mean age
58+/-19 years), accounting for an average incidence of 1.14 episodes per 10,000
patient-days per year. The most common reasons for hospitalization were solid
neoplasia (21%), trauma (17%), abdominal diseases requiring surgery (13%), and
cardiovascular diseases (13%). No patient was neutropenic within 3 weeks prior to
the onset of candidemia. One hundred thirty patients were hospitalized in
intensive care units, 47 patients in surgical wards, and 12 patients in medical
wards. Candida albicans was the most frequently isolated pathogen, accounting for
54% of fungal isolates, followed by Candida parapsilosis (23%), Candida glabrata
(7%), Candida tropicalis (5%), Candida pelliculosa (4%), Candida lusitaniae (1%),
Candida humicula (1%), and other non-albicans Candida spp. (5%). Seventy-six
(41%) patients received adequate antifungal therapy. Seventy-one (58%) of the 123
evaluable patients with central venous catheters underwent line removal; 51 of
them had catheter-related candidemia. The 30-day crude mortality rate was 45%.
Older age, hospitalization in an intensive care unit, a longer duration of
candidemia, retention of central lines, and inadequate antifungal therapy were
significantly associated with poor outcome. In the present study, nosocomial
candidemia was a frequent and relatively underestimated illness. Adequate
antifungal therapy and central line removal independently reduced the high
mortality of the disease.
PMID- 11014623
TI - Isolation of Kingella kingae from synovial fluids using four commercial blood
culture bottles.
AB - According to the literature, Kingella kingae may be an underdiagnosed cause of
joint and bone infections in children. The use of the Bactec blood culture system
for culture of joint fluids has dramatically improved the isolation of this
fastidious bacterium. The aim of this study was to test the recovery rate and
detection time of four commercial blood culture systems: three different
BacT/Alert (Organon Teknika, USA) bottles and one Bactec (Becton Dickinson
Microbiology Systems, USA) bottle, all inoculated with Kingella kingae strains
mixed with pooled synovial fluids. For each strain the same inoculum and volume
of synovial fluid was distributed into each of the four bottles. All 24 strains
tested grew in the BacT/Alert Aerobic (100%) and the BacT/Alert Pedi-BacT (100%)
bottles. Twenty-one strains grew in the BacT/Alert FAN aerobic (88%) bottle, and
15 strains grew in the Bactec Plus Aerobic F (63%) bottle, in both systems within
12 days (P<0.01). The Kingella kingae strains were first detected in the
BacT/Alert Pedi-BacT bottles (P<0.001). The results were reproducible. The
BacT/Alert blood culture bottles were superior to previously described blood
culture systems in isolating Kingella kingae from synovial fluid, even with small
inoculums and small volumes of synovial fluid.
PMID- 11014624
TI - In vitro zones of inhibition of coated vascular catheters predict efficacy in
preventing catheter infection with Staphylococcus aureus in vivo.
AB - This report summarizes data from 35 rabbit model experiments investigating the
relationship between in vitro anti-infective catheter coating zones of inhibition
and in vivo efficacy. The rabbit model studies involving 15 anti-infective
coatings demonstrate an inverse correlation between the sizes of zones of
inhibition of Staphylococcus aureus and both the quantity of Staphylococcus
aureus removed from the catheter and the risk of a purulent infection. The review
of seven previously published clinical trials reveals that the use of anti
infective coated catheters, efficacious in the rabbit model, was associated with
a higher success rate than the use of uncoated catheters in preventing both
Staphylococcus aureus catheter colonization (odds ratio: 1.28; 95% confidence
interval: 0.84-1.93) and Staphylococcus aureus catheter-related bloodstream
infection (odds ratio: 3.07; 95% confidence interval: 0.98-9.60) in humans. These
findings strongly suggest a correlation between zones of inhibition and in vivo
efficacy. In vitro zones of inhibition may serve as a useful screening test for
evaluating new anti-infective coatings.
PMID- 11014625
TI - Evaluation of the Vitek 2 system for susceptibility testing of Streptococcus
pneumoniae isolates.
AB - Vitek 2 (bioMerieux, France) is a new commercial system that allows rapid
identification and rapid determination of the minimum inhibitory concentration
(MIC) of Streptococcus pneumoniae by monitoring the growth kinetics of the
organisms in microwells. The accuracy of the Vitek 2 system in susceptibility
testing was evaluated by determining the MICs of 50 penicillin-susceptible and
150 intermediate or penicillin-resistant Streptococcus pneumoniae isolates and
comparing the results with those obtained using the agar dilution method. The
essential agreement between the Vitek 2 system and the reference method was 91%
for penicillin, 93% for cefotaxime and ceftriaxone, and more than 94% for
amoxicillin, erythromycin, ofloxacin, co-trimoxazole, tetracycline, and imipenem.
One very major error (1.1%) and one major error (0.9%) were obtained for
tetracycline. The minor error rate for penicillin of 19.3% was mainly due to
intermediate category isolates (n = 29) being identified as resistant and
susceptible isolates (n = 6) being identified as intermediate by the commercial
system. The minor error rates for amoxicillin, cefotaxime, ceftriaxone, imipenem,
and ofloxacin were 25.4%, 25.4%, 29.4%, 19.2%, and 31.5%, respectively.
Vancomycin, tetracycline, co-trimoxazole, and erythromycin showed minor error
rates of 0-6.1%. In conclusion, Vitek 2 shows good agreement with the reference
method, as demonstrated by the low numbers of major errors, but it has a tendency
to overestimate MICs, resulting in minor errors.
PMID- 11014626
TI - Response of lymphocyte subsets in patients under treatment for tuberculosis.
AB - Thirty-six immunocompetent patients with tuberculosis underwent six sequential
measurements of blood lymphocyte subsets after the onset of therapy. Two
different responses were observed, depending on each patient's initial lymphocyte
count. Patients with initial lymphocytopaenia showed a marked increase in all
lymphocyte subpopulations shortly after the initiation of treatment, whereas
those without lymphocytopaenia showed a decrease in the cell counts during the
initial 2 months, followed by a slow increase during the following 4 months. The
lymphocytes as a whole and all lymphocyte subsets showed remarkably parallel
curves in each group. These results strongly suggest that the lymphocytic
responses to tuberculosis involve all lymphocyte subsets, not only the T or CD4+
lymphocytes as previously thought.
PMID- 11014627
TI - Molecular typing of bacteria directly from cerebrospinal fluid.
AB - Using Streptococcus pneumoniae as an example, the ability of multilocus sequence
typing (MLST) to characterise isolates directly from cerebrospinal fluid (CSF)
was investigated. A nested multiplex polymerase chain reaction method that
amplifies the seven housekeeping gene fragments used for pneumococcal MLST was
applied to 30 CSF samples from suspected cases of bacterial meningitis. The
fragments were amplified from all 14 samples from which Streptococcus pneumoniae
was cultured, and, after direct sequencing, the allelic profiles obtained from
ten of the samples corresponded to those of clones previously associated with
invasive pneumococcal disease. MLST could also predict the penicillin
susceptibility and serotype of the CSF isolates.
PMID- 11014628
TI - Detection of Isospora belli by polymerase chain reaction using primers based on
small-subunit ribosomal RNA sequences.
AB - The aim of the present study was to use small-subunit (SSU)-rRNA sequences of
Isospora belli to design specific primer pairs and a hybridization probe for the
detection of Isospora belli in human samples by PCR and Southern blot
hybridization. PCR amplification with the primer pairs produced correct DNA
fragments with target DNA from samples of Isospora belli-infected patients and
from cloned SSU-rRNA of Isospora belli. The nature of the PCR products was
confirmed by Southern blot hybridization. No amplification was seen with template
DNA extracted from other parasites. Although Isospora belli infections can be
easily diagnosed using light microscopy, molecular-based techniques may prove
useful as an additional diagnostic tool.
PMID- 11014629
TI - In vitro activity of ABT-773 against anaerobic bacteria.
AB - The purpose of the study reported here was to determine the in vitro activity of
ABT-773 compared with that of other antimicrobial agents against anaerobic
bacteria. The activity of ABT-773 was investigated against 354 clinical isolates
of anaerobic bacteria by the agar dilution method and was compared with that of
azithromycin, clarithromycin, roxithromycin, erythromycin, cefoxitin, imipenem,
clindamycin and metronidazole. ABT-773 and imipenem were the most active
antimicrobial agents tested.
PMID- 11014630
TI - Prosthetic valve endocarditis caused by Mycoplasma hominis.
AB - Mycoplasma hominis endocarditis is extremely uncommon and difficult to diagnose.
Atypical growth characteristics in routine bacterial culture and an inability to
demonstrate the organism using Gram staining can lead to a delayed diagnosis of
Mycoplasma hominis infections, and the organism is often missed. This report
describes a patient with Mycoplasma hominis prosthetic valve endocarditis. The
microorganism was recovered from the mitral prosthesis but was missed in blood
cultures. This finding suggests that Mycoplasma hominis should be considered in
the differential diagnosis of culture-negative endocarditis.
PMID- 11014631
TI - Otitis externa due to Trichoderma longibrachiatum.
PMID- 11014632
TI - Mixed community-acquired fungal infection in an apparently healthy patient.
PMID- 11014633
TI - Detection of Pneumocystis carinii DNA in patients with chronic lung diseases.
PMID- 11014635
TI - Molecular analyses of possible mechanisms coding for low-level mupirocin
resistance in clinical Staphylococcus aureus isolates.
PMID- 11014634
TI - In vitro activity of a new liposomal nystatin formulation against opportunistic
fungal pathogens.
PMID- 11014636
TI - Oral leishmaniasis in an HIV-infected patient.
PMID- 11014637
TI - Understanding rejection of xenografts.
PMID- 11014638
TI - Epithelial re-growth is associated with inhibition of obliterative airway disease
in orthotopic tracheal allografts in non-immunosuppressed rats.
AB - BACKGROUND: Because epithelial cells are targets of alloimmune injury leading
ultimately to airway obliteration, we tested whether epithelial re-growth could
prevent obliterative airway disease (OAD) in orthotopic tracheal allografts.
METHODS: Brown Norway tracheal segments were orthotopically transplanted into
nonimmunosuppressed Lewis rats. Allografts were removed on days 2-10 (n=13), 30
(n=4), and 60 (n=5) for histology, computerized morphometry (obliteration), and
immunohistochemical detection of mononuclear cells, smooth muscle alpha-actin,
and tissue phenotype. Normal tracheas, host tracheas, and heterotopically
transplanted allografts served as controls. RESULTS: Orthotopic allografts
removed on days 2-10 exhibited epithelial damage and re-growth and mononuclear
cell infiltration. On days 30 and 60, partially ciliated cuboidal or attenuated
epithelium completely covered the lumen. Although mononuclear cells declined,
numerous T cells with a high CD4/CD8 ratio were found in the epithelium till day
60. Orthotopic allograft epithelium expressed donor phenotype on day 7, but
recipient phenotype on days 30 and 60. Despite subepithelial alpha-actin positive
myofibroblast proliferation, obliteration did not progress from day 7 to 30 and
60 (35, 30, and 33%, respectively). Although more than in normal or host
tracheas, the obliteration in orthotopic allografts on days 30 and 60 was
significantly less (P<0.001) than in heterotopic allografts. CONCLUSIONS: We
describe, for the first time, longterm patency of fully histoincompatible
orthotopic tracheal allografts in nonimmunosuppressed rats. Despite acute
alloimmune injury and induction of myofibroblast proliferation, epithelial re
growth from the host limited the progression of OAD, thus emphasizing the role of
epithelium in the control of airway obliteration.
PMID- 11014639
TI - Recombinant adenoviral mediated CD39 gene transfer prolongs cardiac xenograft
survival.
AB - BACKGROUND: Extracellular ATP and ADP may be important mediators of vascular
inflammation and thrombosis. Nucleoside triphosphate diphosphohydrolase (NTPDase
or CD39) is a vascular ectoenzyme that hydrolyses ATP and ADP; however, this
activity is lost during reperfusion injury. We show that the supplementation of
NTPDase activity within xenograft vasculature using CD39 recombinant adenoviruses
(AdCD39) has protective effects in vivo. METHODS: Recombinant adenoviruses
containing human CD39 or beta-galactosidase (Adbeta-gal) encoding genes were
constructed. Hartley guinea pig coronary arteries were perfused ex vivo with
University of Wisconsin solution containing 10(9) plaque-forming units of the
recombinant adenovirus. Infected grafts were then implanted in the abdomen of
complement depleted Lewis rats. RESULTS: NTPDase activities decreased in all
grafts within the first 24 hr and subsequently recovered only in those hearts
infected with AdCD39. Immunohistological examination of AdCD39-infected grafts
confirmed successful CD39 gene transfer into the endocardium and
macrovasculature. Expression of CD39 modestly prolonged graft survival (90.2+/
5.4 hr, mean+/-SD, n=5) when compared with Adbeta-gal-infected grafts (67.4+/-5.4
hr, P<0.005) and perfusion controls (66.4+/-5.2 hr; P<0.005). CONCLUSIONS:
Recombinant adenoviral infection can induce expression of CD39 within cardiac
xenografts and provide survival benefits in vivo. Our data show that ex vivo
infection by recombinant adenovirus vectors can result in vascular expression of
a potential therapeutic agent.
PMID- 11014640
TI - Successful prevention of autoimmune disease by transplantation of adequate number
of fully allogeneic hematopoietic stem cells.
AB - BACKGROUND: We have previously shown successful engraftment of allogeneic
hematopoietic stem cells (HSCs) when transplanted across the major
histocompatibility antigen barriers if transplanted along with a preparation of
facilitator cells (osteoblasts). We have investigated whether or not fully
allogeneic HSCs from healthy mouse donors prevent the development of
autoimmunities in the autoimmune-prone W/B F1 mice. METHODS: W/B F1 is a strain
of mice that spontaneously develop autoimmunities, a coronary vascular disease,
thrombocytopenia, and systemic lupus-like syndrome. The 6- to 8-week-old (before
the onset of the disease) W/B F1 mice have been transplanted with either a
preparation of HSCs alone, or along with facilitator cells from MHC-incompatible
autoimmune-resistant BALB/c mice, then followed to determine longterm survival
and whether or not they developed signs of the autoimmune disease. RESULTS: The
number of the transplanted HSCs acts as the determining factor in achieving
successful and durable engraftment. Survival of the W/B F1 mice significantly
improved by transplantation of increasing numbers of HSCs, either alone or along
with facilitator cells. When W/B F1 mice were transplanted with 2-5 million HSCs,
more than 1-year survival was 100%, all the transplanted mice were fully
engrafted with allogeneic HSCs, and were free of signs of the autoimmune disease.
Histological sections of the hearts, lungs, and kidneys of the transplanted mice
showed absence of the autoimmune-associated pathology. CONCLUSIONS: We thus
report herein the successful prevention of autoimmune disease by transplantation
of a sufficiently large number of purified fully allogeneic HSCs in W/B F1 mice.
PMID- 11014641
TI - Increased glomerular deposits of von Willebrand factor in chronic, but not acute,
rejection of primate renal allografts.
AB - BACKGROUND: In our previously described primate renal allograft model, T cell
ablation leads to long-term graft survival. The role of endothelial cell
alteration in chronic rejection was examined in our model. METHODS: Renal
transplants were performed in rhesus monkeys using a T cell- depleting
immunotoxin, FN18-CRM9. Sections from 10 rejected kidneys (5 acute and 7 chronic
rejection) were examined after immunohistochemical staining for expression of
endothelium-related proteins [von Willebrand factor (vWF), CD62P, and CD31],
fibrinogen, and a macrophage marker (CD68). Glomerular staining for each antigen
was graded on a semiquantitative scale. RESULTS: Intense staining for vWF was
consistently observed in glomerular endothelium, subendothelium, and mesangium in
all kidneys removed due to chronic rejection. vWF staining was weak in kidneys
showing acute rejection. The difference in glomerular staining was statistically
significant. Staining for vWF in extraglomerular vessels was nearly identical in
kidneys showing acute and chronic rejection. Expression of CD62P was increased in
extraglomerular vessels in allografts with chronic rejection, but the glomeruli
showed little or no staining. There was no significant difference in the
glomerular staining for CD62P or CD31 in organs showing acute and chronic
rejection. Fibrinogen staining of glomerular mesangium was seen in kidneys with
chronic rejection. Macrophages (CD68+) infiltrating glomeruli were more numerous
in kidneys showing chronic rejection. CONCLUSION: Increased glomerular deposition
of vWF in renal allografts showing chronic rejection, without increased staining
for CD62P or CD31, suggests increased constitutive secretion of vWF from
endothelial cells as a component of the mechanism of chronic rejection in our
model.
PMID- 11014642
TI - Plasmapheresis and intravenous immune globulin provides effective rescue therapy
for refractory humoral rejection and allows kidneys to be successfully
transplanted into cross-match-positive recipients.
AB - BACKGROUND: Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain
recalcitrant conditions without effective treatments, and usually result in graft
loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in
many different clinical settings. Intravenous gamma globulin (IVIG) has been used
to suppress alloantibody and modulate immune responses. Our hypothesis was that a
combination of PP and IVIG could effectively and durably remove donor-specific,
anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively
desensitizing recipients who had positive crossmatches with a potential live
donor. METHODS: The study patients consisted of seven live donor kidney
transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one
or more mismatched donor HLA antigens. The patients segregated into two groups:
three patients were treated for established AHR (rescue group) and four cross
match-positive patients received therapy before transplantation (preemptive
group). RESULTS: Using PP/IVIG we have successfully reversed established AHR in
three patients. Four patients who were cross-match-positive (3 by flow cytometry
and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal
transplantation utilizing their live donor. The overall mean creatinine for both
treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17
116 weeks). CONCLUSIONS: In this study, we present seven patients for whom the
combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab
specific for donor HLA antigens. Furthermore, this protocol shows promise for
eliminating DSA preemptively among patients with low-titer positive antihuman
globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches,
allowing the successful transplantation of these patients using a live donor
without any cases of HAR.
PMID- 11014643
TI - CD8+ T cells are capable of rejecting pancreatic islet xenografts.
AB - BACKGROUND: In this study, the capacity of CD8+ T cells to act as a potential
effector mechanism in pancreatic xenograft rejection was examined. METHODS: The
fate of pancreatic islet xenografts was studied in mice deficient in MHC class II
molecules and CD4+ T cells. Fetal pig pancreas (FPP) or Wistar rat islets (RI)
were transplanted into nondiabetic or streptozotocin-induced diabetic I-A knock
out (CII K/O) mice. RESULTS: CII K/O mice were capable of rejecting both RI and
FPP grafts. RI graft survival was not prolonged compared with wild type C57BL/6
controls. However, FPP grafts did survive longer in CII K/O recipients than in
C57BL/J6 mice. Both RI and FPP graft rejection were CD8+ T-cell phenomena in CII
K/O mice, as anti-CD8 monoclonal antibody prolonged graft survival, there were
increased CD8+ T cells in the grafts and spleens of CII K/O recipients, and cell
mediated cytotoxicity was a CD8+ T-cell phenomenon associated with activation of
the perforin/granzyme B system. By contrast, RI and FPP graft rejection was a
CD4+ T cell-dependent phenomenon in wild type C57BL/6 mice with graft survival
prolonged by anti-CD4 monoclonal antibody. There were increased numbers of CD4+ T
cells, and cell-mediated cytotoxicity was a CD4+ T-cell phenomenon associated
with activation of the Fas/FasL lytic pathway. CONCLUSIONS: The results
demonstrate that, in the absence of CD4+ T cells, CD8+ T cells were capable of
rejecting both rat and pig pancreatic islet xenografts.
PMID- 11014644
TI - Mixed chimerism, heart, and skin allograft tolerance in cyclophosphamide-induced
tolerance.
AB - We elucidated the possible role of chimerism in skin and heart allograft
tolerance using cyclophosphamide (CP)-induced tolerance. When C3H (H-2k; Thy1.2,
Mls-1b) mice were i.v. primed with 1x10(8) spleen cells (SC) from H-2 matched AKR
(H-2k; Thy1.1, Mls-1a) mice and then treated i.p. with 200 mg/kg of CP, the
survivals of both AKR skin grafts and heart grafts (HG) were permanently
prolonged in a tolerogen-specific fashion. After this treatment, a minimal degree
of mixed chimerism, the clonal destruction of Mls-1a-reactive CD4+Vbeta6+ T cells
in the periphery, and the clonal deletion of Vbeta6+ thymocytes were all
observed. When AKR SC and 100 mg/kg CP were used for conditioning, the AKR HG
were permanently accepted, but the survival of the AKR skin grafts was only
mildly prolonged. The clonal destruction of CD4+Vbeta6+ T cells in the periphery
and the intrathymic clonal deletion of Vbeta6+ thymocytes were induced in both
the SC and the 100 mg/kg CP-treated C3H mice. A minimal degree of mixed chimerism
was detectable at 4 and 12 weeks after AKR SC and 100 mg/kg CP treatment, and
still did not disappear at 40 weeks. The degree of mixed chimerism induced with
SC and 100 mg/kg CP was significantly lower than that with SC and 200 mg/kg CP
during the observation. No posttransplant cardiac allograft vasculopathy (CAV)
was observed to develop, while both the Th1 type (interferon-gamma) and Th2 type
(interleukin-4 and -10) cytokine expressions decreased in the AKR HG of the
tolerant C3H mice treated with both AKR SC plus 200 mg/kg CP, and AKR SC plus 100
mg/kg CP. A second set of skin grafts from donor AKR mice survived for more than
100 days in a tolerogen-specific fashion in all C3H mice treated with AKR SC and
200 mg/kg CP and also accepted the AKR HG for over 200 days, while 80% of the C3H
mice treated with AKR SC and 100 mg/kg CP and accepted the AKR HG for more than
200 days. These results strongly suggested the following conclusions: 1) the
degree of chimerism can strongly influence the induction of skin and heart
allograft tolerance, 2) posttransplant CAV does not develop in the donor HG
maintained by chimerism-based CP-induced tolerance, 3) the mRNA expression of
both Th1 and Th2 type cytokine decreased in the donor HG maintained by chimerism
based CP-induced tolerance, and 4) the induction of skin allograft tolerance is
more difficult than the prevention of posttransplant CAV.
PMID- 11014645
TI - Alpha-gal-independent dual recognition and activation of xenogeneic endothelial
cells and human naive natural killer cells.
AB - BACKGROUND: Interaction between vascularized xenograft and host immune system is
thought to occur via Galactose alpha (1,3) Galactose (Gala 1,3 gal) structures
decorating the xenograft. METHODS: We raised anti-Gala 1,3 gal-BSA polyclonal
antibodies in baboons and investigated effect(s) of these antibodies as well as
soluble Gala 1,3 gal-BSA on human naive natural killer (NK) cell interactions
with porcine aortic endothelial cells. RESULTS: We demonstrate that human naive
(unstimulated) NK cells recognize xenogeneic endothelial cells under conditions
where binding to the Gala 1,3 gal structures is minimized by the presence of
blocking anti-Gala 1,3 gal IgG or soluble Gala 1-3 gal and in the absence of
xenoreactive natural antibodies and complement. After xenogeneic encounter both
endothelial cells and human NK cells are activated. Endothelial cell activation
is rapid and is manifested initially by an intraendothelial calcium transient and
subsequently by expression of P-selectin and vascular endothelial cell adhesion
molecule-1 on the xenoendothelium surface. NK cell activation is manifested by
increased expression of perforin and increased cytotoxicity towards the
xenoendothelium. Neither recognition nor activation of the xenoendothelium was
affected by the introduction of either anti-Gala 1,3 gal IgG or soluble Gala 1-3
gal. CONCLUSION: Our data provide evidence that innate immune cells, such as NK
cells, recognize and activate xenoendothelial cells independently of Gala 1-3 gal
structures and raise the possibility of novel interactive sites on both human
naive NK cells and discordant xenogeneic endothelium.
PMID- 11014646
TI - Interleukin-13 protects endothelial cells from apoptosis and activation:
association with the protective genes A20 and A1.
AB - BACKGROUND: Chronic rejection is the major obstacle to long-term survival of
allografts and is associated with graft endothelial cell activation and
apoptosis. Recent reports have found an association between graft survival,
presence of Th2 cytokines, and expression by endothelial cells of cytoplasmic
"protective" molecules that prevent apoptosis and down-regulate the inflammatory
process. METHODS: Cultured human umbilical vein endothelial cells (HUVEC) were
used. Apoptotic cells were detected by staining with FITC-annexinV followed by
flow cytometry. Expression of vascular cell adhesion molecule-1, E-selectin, and
intercellular adhesion molecule-1 were also measured by flow cytometry.
Transcripts were detected by reverse transcription-PCR and quantitation was
achieved by co-amplification of competing, internal standard RNA. RESULTS: We
demonstrate that exposure of HUVEC to interleukin (IL)-13 for 72 hr afforded
partial protection from apoptosis induced by tumor necrosis factor
alpha/cycloheximide or serum starvation. Pretreatment with IL-13 also modulated
induction of E-selectin after acute exposure to tumor necrosis factor-alpha or IL
1alpha. Protection was associated with transcription of the genes A1 and A20.
Prolonged treatment with IL-13 had minimal proinflammatory effects and did not
induce expression of E-selectin or vascular cell adhesion molecule-1 or increase
intercellular adhesion molecule-1 above basal levels. CONCLUSIONS: Our data
provide a possible explanation for the observed association between Th2 cytokines
and expression of protective genes in the endothelium of long-surviving
allografts and xenografts.
PMID- 11014647
TI - Specific depletion of preformed IgM natural antibodies by administration of anti
mu monoclonal antibody suppresses hyperacute rejection of pig to baboon renal
xenografts.
AB - BACKGROUND: The elimination of circulating anti-porcine preformed antibodies is
crucial for avoiding hyperacute vascular rejection (HAVR) of primarily
vascularized xenograft in discordant pig to baboon model. Previously described
methods used for eliminating natural antibodies, however, constantly removed both
anti-porcine IgM and IgG antibodies, as well as often complement proteins. To
study specifically the role of preformed anti-porcine IgM antibodies, a specific
anti-IgM monoclonal antibody (mAb) has been designed and evaluated in vivo.
METHODS: Iterative injections of anti-IgM mAb (LO-BM2) at high dose (20 mg/kg)
depleted to undetectable level the circulating IgM and therefore anti-porcine IgM
antibodies but did not change the concentration of anti-pig IgG antibodies. The
serum concentration of IgM and IgG antibodies was assessed by ELISA and the level
of anti-pig natural IgM and IgG antibodies by flow cytometry (FC). Anti-rat
sensitization was assessed by specific ELISA as well as the serum concentration
of LO-BM2. RESULTS: Iterative injections of LO-BM2 allowed to specifically
eliminate the anti-porcine IgM antibodies to undetectable levels at ELISA.
Despite a normal serum level of anti-porcine IgG and complement proteins, HAVR
was avoided. Without immunosuppression, the specific elimination of preformed
anti-porcine IgM prolonged the survival of a renal xenograft in baboon up to 6
days, whereas without IgM antibody elimination, the renal xenografts were
hyperacutely rejected within hours. The lost of activity of LO-BM2 after 10 days
was concomitant to an IgM and IgG antibody rebound, which caused an acute
vascular rejection of the xenograft. CONCLUSION: Specific elimination of natural
anti-porcine IgM antibodies allows to avoid HAVR of a pig to baboon renal
xenograft, whereas anti-porcine IgG antibodies and complement proteins were
present in the serum. This result confirms previous in vitro reports and
demonstrates for the first time in vivo that preformed IgM antibodies alone are
responsible for HAVR, while preformed anti-porcine IgG antibodies are unable
alone to cause HAVR. Anti-IgM therapy appears as an important tool to transiently
but completely eliminates xeno-IgM antibodies in vivo.
PMID- 11014648
TI - Local production of anti-CD4 antibody by transgenic allogeneic grafts affords
partial protection.
AB - BACKGROUND: Immunosuppressive drugs and anti-lymphocyte antibody are used
clinically to suppress cellular rejection responses. However, these systemic
regimens often led to general immunodeficiency and thus increased susceptibility
to opportunistic infection and neoplasia. Immunosuppressive molecules delivered
locally may be a way of inhibiting rejection responses, whereas systemic immunity
is preserved. To achieve protective local immunosuppression, we produced a graft
secreting its own immunomodulator, by deriving transgenic mice expressing a
chimeric anti-CD4 antibody (GK2c) in the pancreas. METHODS AND RESULTS:
Transgenic mice in bml genetic background expressing a modified anti-mouse CD4
antibody (GK2c) under two promoters have been produced. Tissue expression of GK2c
was detected by immunoperoxidase staining. Under the cytomegalovirus promoter,
there was abundant GK2c expression in pancreatic exocrine tissue. Under the rat
preproinsulin II promoter, there was abundant GK2c expression in pancreatic
endocrine tissue only. High-expression transgenic lines had 10-100 microg/ml GK2c
in blood plasma. By flow cytometry, these transgenic mice were devoid of CD4+
cells in their peripheral lymphoid organs. To test transgenic mice as donors,
fetal pancreata from transgenic mice were grafted into fully allogeneic CBA mice
under the kidney capsule, transgenic grafts had prolonged survival compared with
control non-transgenic grafts. Furthermore, GK2c transgenic grafts had reduced
infiltration with an absence of CD4+ cells at the graft site without any effect
on the cell composition in lymphatic tissues. CONCLUSION: Transgenic grafts that
secrete anti-CD4 antibody can afford some protection against graft rejection,
while only affecting the CD4 population at the graft site.
PMID- 11014649
TI - Intragraft interleukin-4 mRNA expression after short-term CD154 blockade may
trigger delayed development of transplant arteriosclerosis in the absence of CD8+
T cells.
AB - BACKGROUND: It has recently been shown that, although anti-CD154 induces CD4+ T
cell tolerance, it is unable to prevent allograft rejection mediated by CD8+ T
cells. We have also shown that anti-CD154 monotherapy does not protect the graft
from the development of transplant arteriosclerosis even in the absence of CD8+ T
cells. This study was designed to investigate and characterize possible
mechanisms responsible for the development of transplant arteriosclerosis after
CD154 blockade in the absence of CD8+ T cells. METHODS: C57BL/6 (H2b) recipients
received a fully MHC-mismatched BALB/c donor aorta (H2d). Animals were either
treated with anti-CD154 monoclonal antibody (mAb) in the presence or absence of
CD8 T cells. Histology, morphometric measurements, immunohistochemistry, and the
production of alloantibodies (IgM, IgG1, IgG2a) were analyzed on days 14, 30, and
50 after transplantation. Cytokine production within the graft was investigated
by competitive reverse transcription-polymerase chain reaction on day 14.
RESULTS: Combined treatment with anti-CD154 and a depleting CD8 mAb resulted in a
delay in the development of transplant arteriosclerosis (intimal proliferation:
33+/-10% vs. 67+/-11% untreated control, day 30) but ultimately did not prevent
its progression (intimal proliferation: 55+/-10% vs. 78+/-9% untreated control,
day 50). Although there was a significant decrease in the number of CD4+, CD11b+,
and CD40+ graft-infiltrating cells and a reduction in the formation of donor
specific IgG1 alloantibodies in recipients treated with anti-CD154 and anti-CD8
mAbs, mRNA for interleukin (IL)-4 was increased, suggesting a shift in the
intragraft cytokine profile towards a Th2-like pattern. CONCLUSIONS: Our data
provide evidence that short-term CD154 blockade is insufficient to prevent
transplant arteriosclerosis, even in combination with CD8+ T-cell depletion.
Moreover, the increased expression of the Th2 cytokine interleukin-4 within the
graft may be responsible for the development of transplant arteriosclerosis in
the long term.
PMID- 11014650
TI - The pig analogue of CD59 protects transgenic mouse hearts from injury by human
complement.
AB - BACKGROUND: It has been proposed that hyperacute rejection (HAR) of pig-to
primate vascularized xenografts is due in large part to ineffective regulation of
recipient complement by pig complement regulatory proteins (CRPs), and indeed
transgenic expression of human CRPs in pigs can prevent hyperacute rejection.
However, at least one pig CRP (CD59) efficiently regulates human complement in
vitro, suggesting that it is the level of expression of a particular CRP(s)
rather than cross-species incompatibility that explains the HAR of porcine
xenografts. We investigated the relative effectiveness of transgenically
expressed pig and human CD59 in providing protection of mouse hearts from human
complement in an ex vivo setting. METHODS: Transgenic mice expressing pig CD59 or
human CD59 under the control of the human ICAM-2 promoter, which restricts
expression in tissues to vascular endothelium, were used. Hearts from mice
expressing similar levels of pig CD59 or human CD59 were perfused ex vivo with
10% human plasma and heart function was monitored for 60 min. Sections of
perfused hearts were examined for deposition of the membrane attack complex
(MAC). RESULTS: Control nontransgenic hearts (n=5) were rapidly affected by the
addition of human plasma, with mean function falling to less than 10% of the
initial level within 15 min. In contrast, hearts expressing either pig CD59 (n=6)
or human CD59 (n=8) were protected from plasma-induced injury, maintaining 31 and
35% function, respectively, after 60 min of perfusion. MAC deposition was
markedly reduced in both pig CD59 and human CD59 transgenic hearts compared to
nontransgenic control hearts. CONCLUSIONS: When highly expressed on endothelium
in transgenic mice, pig CD59 provided equivalent protection to human CD59 in a
model of human complement-mediated xenograft rejection. Thus supranormal
expression of endogenous porcine CRPs may be a feasible alternative to the
expression of human CRPs in preventing HAR of pig-to-primate xenografts.
PMID- 11014651
TI - Sirolimus (rapamycin) halts and reverses progression of allograft vascular
disease in non-human primates.
AB - BACKGROUND: Current immunosuppressive protocols fail to prevent chronic rejection
often manifested as graft vascular disease (GVD) in solid organ transplant
recipients. Several new immunosuppressants including sirolimus, a dual function
growth factor antagonist, have been discovered, but studies of drug efficacy have
been hampered by the lack of a model of GVD in primates, as a prelude to clinical
trials. As described earlier, we have developed a novel non-human primate model
of GVD where progression of GVD is quantified by intravascular ultrasound (IVUS).
METHODS: Twelve cynomolgus monkeys underwent aortic transplantation from blood
group compatible but mixed lymphocyte reaction-mismatched donors. To allow the
development of GVD in the allograft, no treatment was administered for the first
6 weeks. Six monkeys were treated orally with sirolimus from day 45 after
transplantation to day 105. RESULTS: Progression of GVD measured as change in
intimal area from day 42 to 105 was halted in sirolimus-treated monkeys compared
to untreated monkeys (P<0.001, general linear model). On day 105, the intimal
area +/- SEM was 3.7+/-1.0 and 6.4+/-0.5 mm2, respectively (P<0.05, t test). The
magnitude of allograft intimal area on day 105 correlated inversely with
sirolimus trough levels (R2=0.67, P<0.05). Regression of the intimal area was
seen in four of six sirolimus-treated monkeys, which was significantly different
from the untreated monkeys (P<0.05). CONCLUSIONS: Our results in the first non
human primate model of GVD showed that treatment with sirolimus not only halted
the progression of preexisting GVD but also was associated with partial
regression. Sirolimus trough blood levels were correlated with efficacy.
Therefore, sirolimus has the potential to control clinical chronic allograft
rejection.
PMID- 11014652
TI - Single injection of insulin delays the recurrence of diabetes in syngeneic islet
transplanted diabetic NOD mice.
AB - BACKGROUND: Insulin has been implicated in the pathogenesis of type 1 diabetes
and oral administration of insulin has been shown to delay the onset of diabetes
in NOD mice. In this study we determined whether a single footpad injection of
insulin will protect syngeneic islet grafts from autoimmune destruction when
placed under the kidney capsule of diabetic NOD mice. METHODS: Five hundred
islets were transplanted under the kidney capsule of diabetic female NOD mice in
conjunction with a single footpad injection of either pork insulin in saline or
mixed with incomplete Freund's adjuvant (IFA). Control groups received either IFA
or saline alone. RESULTS: Seven of 11 animals (63.6%) given insulin in IFA
exhibit long-term graft survival (>75 days; mean +/- SEM >85.4+/-16.1) whereas
only 3 of 12 animals (25.0%) in the IFA group had graft survival longer than 75
days (mean +/- SEM >41.9+/-12.8 days). In contrast, none of the animals that
received insulin in saline (17.3+/-2.5 days) and saline only (16.1+2.0 days)
exhibit prolonged graft survival. CONCLUSION: These results suggest that a single
footpad injection of insulin can protect the islet graft from immune attack in
NOD mice.
PMID- 11014653
TI - Tacrolimus-associated mutism after orthotopic liver transplantation.
AB - BACKGROUND: Mutism/speech apraxia has been well documented as a toxic effect of
cyclosporine after liver transplantation but has been reported only rarely with
tacrolimus. Brain imaging with magnetic resonance or computed tomography has
failed to demonstrate abnormalities in affected patients. METHODS: We present the
first example of an acute onset of loss of speech associated with a sudden
elevation of serum tacrolimus level after successful orthotopic liver
transplantation. We also describe the positron emission tomography (PET) scan of
this patient's brain. RESULTS: PET scan imaging of the brain was abnormal,
demonstrating decreased metabolism in the posterior temporo-parieto-occipital
regions. Statistical probability mapping revealed additional areas of
hypometabolism in the cingulate gyrus. CONCLUSIONS: PET scan revealed
abnormalities of the brain in a patient with tacrolimus-induced mutism. The
cingulate gyrus may play a role in the mutism/speech apraxia syndrome seen with
cyclosporine/tacrolimus neurotoxicity.
PMID- 11014654
TI - Intrahepatic anastomosis formation between the hepatic veins in the graft liver
of the living related liver transplantation: observation by Doppler
ultrasonography.
AB - In living related liver transplantation, the right lobe has come to be used as a
graft to meet the metabolic demands of adult or adolescent recipients. In
harvesting the right lobe as a graft, however, there is controversy as to whether
or not the middle hepatic vein (MHV) should be included and reconstructed.
Anatomical intrahepatic anastomosis between the right hepatic vein (RHV) and MHV
is considered to exist, but the formation process of this functional anastomosis
has not been demonstrated by Doppler ultrasonography (US). In our case, a right
lobe including a right branch of the MHV was used as a graft. In implanting, the
RHV was anastomosed to the inferior vena cava and the right branch of the MHV was
ligated. Using Doppler US, we checked the blood flow in the hepatic vein after
transplantation. Within 3 days of surgery, no flow was detected in the right
branch of the MHV. A flow around the right branch of the MHV was observed at
postoperative day 6. At postoperative day 9, a reverse flow was detected in which
the right branch of the MHV drained into the RHV via the anastomosis between
them. Based on our results, it appears that a functional intrahepatic anastomosis
between hepatic veins formed gradually within 10 days of ligation of an afferent
branch, during which time the graft function did not deteriorate.
PMID- 11014655
TI - Managing incidents in the cervical screening programme.
PMID- 11014657
TI - Fine needle aspiration cytology (FNAC) of adrenal masses.
AB - Between 1992 and 1998 at the Pathology Section, Cytopathology Unit of the
Department of Oncological and Surgical Sciences of the University of Padova, we
performed one hundred and twelve FNACs of adrenal masses under radiological
guidance and seven intraoperative scrape smears; histological follow-up was
available in 55 cases. Immediate on-site assessment of smears revealed a
satisfactory adequacy rate (92%). With a simple diagnostic tree, we have been
able to classify all smears except one as benign or malignant correctly,
(accuracy 97.6%), differentiation of primary tumours from metastatic depositions
remaining the most difficult task. In our experience FNAC is a safe and accurate
tool in the diagnostic characterization of adrenal masses.
PMID- 11014656
TI - Analysis of proliferating cell fraction determined by monoclonal antibody to M1
subunit ribonucleotide reductase and Ki-67 in relation to p53 protein expression
in fine-needle aspirates from non-Hodgkin's lymphomas.
AB - The purpose of this study was to analyse the proliferative fraction with the
monoclonal antibody M1-R-R to M1-subunit ribonucleotide reductase and with MIB-1
to Ki-67 antigen in relation to p53 protein expression in fine needle aspirates
from B-cell non-Hodgkin's lymphomas. One hundred and thirty-seven cases,
previously diagnosed and sub-typed according to the Kiel classification and
characterized by immunophenotyping, were included in the study. The M-1 subunit
ribonucleotide reductase (M1-R-R), Ki-67 and p53 antigens were detected using
monoclonal antibodies on stored cytospin preparations. There was a good
correlation (r = 0.72) between Ki-67 and M1-R-R positive cell fraction in both
high and low grade lymphomas. High-grade lymphomas had a median percentage of M1
R-R/MIB-1 positive cells of 53.0/73.0 for lymphoblastic, 61.0/52.0 for
immunoblastic and 33.5/41.0 for centroblastic lymphomas, respectively. In low
grade lymphomas figures of median percentage of M1-R-R/MIB-1 were 9.0/15.0 for
centroblastic/centrocytic, 11.0/9.5 for chronic lymphocytic leukaemia, 16.0/27.0
for centrocytic and 12.0/9.0 for immunocytomas, respectively. The median
percentages of M1-R-R/MIB-1 for high and low grade lymphomas were 37.0/50.5 and
11.0/12.0, respectively. In the p53 positive cases the proliferation rate as
measured by staining for M1-R-R and MIB-1 was higher than in p53 negative cases,
but the difference was not statistically significant. The results show that
cytospin material obtained by fine needle aspiration and stored at -70 degrees C
for years can be used reliably for both peroxidase-avidin-biotin and three-step
alkaline phosphatase immunocytochemical staining. In addition, proliferation
fraction determined by M1-R-R monoclonal antibody staining correlates well with
that measured by an established marker for cell proliferation, the Ki-67
antibody. However, the proliferation fraction as measured by the two antibodies
differs in the various subtypes of non-Hodgkin's lymphoma which indicates that
they may contribute different prognostic information.
PMID- 11014658
TI - The usefulness of a panel of immunostains in the diagnosis and differentiation of
metastatic malignancies in pericardial effusions.
AB - Pericardial effusions are not uncommon in patients with an advanced malignancy
Rarely malignancies may present initially with a pericardial effusion.
Cytological examination of pericardial fluid may be valuable in differentiation
of these cases. However, a metastatic tumour in serous effusion may not always
show the functional differentiation of the primary tumour. In such a situation,
although a wide range of special studies have been suggested for the diagnosis of
malignancy we have found the use of a panel of a few common immunostains to be
useful in confirming or suggesting the site of a primary tumour. The material for
this study consisted of 76 pericardial fluids obtained between January 1991 and
October 1998 from 46 males (mean age 59 years) and 30 females (mean age 52
years). Metastatic malignancy was diagnosed in 22 of the 76 patients and in 7/22
cases pericardial effusions were the initial presentation. The subsequent follow
up in the seven cases revealed adenocarcinoma of lung (n = 2), small cell
anaplastic carcinoma of lung (n = 1), squamous cell carcinoma lung (n = 1),
melanoma leg (n = 1), non-Hodgkin's lymphoma retroperitoneal lymph nodes (n = 1)
and carcinoma of the breast (n = 1). Of the remaining 15 cases with a known
history of malignancy, eight had cancers (three adeno; two small cell; one poorly
differentiated, and two squamous cell types) of the lung; breast (n = 3); colon
(n = 1); melanoma (n = 2) and non Hodgkin's lymphoma (n = 1). Immunostains which
were useful in the diagnosis were EMA, CEA, cytokeratin, B72.3, HMB45, vimentin,
S100, LCA, L26 and kappa and lambda light chains.
PMID- 11014659
TI - Exact Touch: a new device for cervical cytology. Comparison with Ayre spatula
plus Cytobrush.
AB - Exact Touch is a new plastic device for the collection of cells from the
ectocervix and endocervix. A total of 189 consecutive women were evaluated, 94
with the Ayre/cytobrush and 95 with Exact Touch. Sampling was performed by only
one clinician, and the slides were analysed by only one cytotechnologist, who had
no information about the sampling method. Our results showed that more
endocervical and metaplastic cells were collected by Exact Touch than by
Ayre/cytobrush.
PMID- 11014661
TI - Continuing education for cytotechnologists: the Australian experience.
AB - The development of a continuing education scheme for cytotechonologists in
Australia is described. The process involved the establishment of a working party
with Terms of Reference to review current practice in Australia and existing
schemes in other parts of the world. The scheme developed takes the form of a
continuing education diary that provides guidelines on the various forms of
continuing education activity and corresponding credit points. The diary also
provides for a record of activity to be kept. The scheme requires bi-annual
submission of personal activity which is logged into a national database. A peer
profile is provided and successful achievement is marked by the issue of a
certificate of participation. The programme has achieved a 57% compliance in its
first year of operation.
PMID- 11014660
TI - The interaction of trichomonas vaginalis with epithelial cells, polymorphonuclear
leucocytes and erythrocytes on vaginal smears: light microscopic observation.
AB - In this study, vaginal smears taken from 400 patients were examined cytologically
using the Papanicolaou technique. Twenty of the 400 patients were detected as
harbouring Trichomonas vaginalis. The interactions of T. vaginalis with
epithelial cells, polymorphonuclear leucocytes (PMNLs) and erythrocytes were
determined at light microscopic level. It was observed that T. vaginalis were
juxtaposed to the epithelial cells and changed shape according to the contours of
the epithelial cell revealing the cytopathic effect of trichomonads on epithelial
cells. Trichomonads attached to PMNLs produced pseudopodia to phagocytose the
cells. Occasionally an amoeboid shaped T. vaginalis organism was seen trailed by
a row of PMNLs. This light microscopic study supports the production by
trichomonads of a chemotactic factor for PMNLs. Phagocytosed erythrocytes were
also seen in the cytoplasm of T. vaginalis, suggesting the need for the patient
to be tested for anaemia.
PMID- 11014662
TI - Educational case report. Cohesive cells in a breast fine needle aspirate.
PMID- 11014663
TI - Endosalpingiosis (mullerianosis) of the bladder: a potential source of error in
urinary cytology.
PMID- 11014664
TI - Reprocessing inadequate breast FNAC 'Cytospin' samples to improve diagnostic
rates--an audit.
PMID- 11014665
TI - George Papanicolaou (1883-1962).
PMID- 11014666
TI - Acinic cell carcinoma arising in pleomorphic adenoma of parotid gland.
PMID- 11014667
TI - A model for experience-dependent changes in the responses of inferotemporal
neurons.
AB - Neurons in inferior temporal (IT) cortex exhibit selectivity for complex visual
stimuli and can maintain activity during the delay following the presentation of
a stimulus in delayed match to sample tasks. Experimental work in awake monkeys
has shown that the responses of IT neurons decline during presentation of stimuli
which have been seen recently (within the past few seconds). In addition,
experiments have found that the responses of IT neurons to visual stimuli also
decline as the stimuli become familiar, independent of recency. Here a
biologically based neural network simulation is used to model these effects
primarily through two processes. The recency effects are caused by adaptation due
to a calcium-dependent potassium current, and the familiarity effects are caused
by competitive self-organization of modifiable feedforward synapses terminating
on IT cortex neurons.
PMID- 11014668
TI - Independent component analysis applied to feature extraction from colour and
stereo images.
AB - Previous work has shown that independent component analysis (ICA) applied to
feature extraction from natural image data yields features resembling Gabor
functions and simple-cell receptive fields. This article considers the effects of
including chromatic and stereo information. The inclusion of colour leads to
features divided into separate red/green, blue/yellow, and bright/dark channels.
Stereo image data, on the other hand, leads to binocular receptive fields which
are tuned to various disparities. The similarities between these results and the
observed properties of simple cells in the primary visual cortex are further
evidence for the hypothesis that visual cortical neurons perform some type of
redundancy reduction, which was one of the original motivations for ICA in the
first place. In addition, ICA provides a principled method for feature extraction
from colour and stereo images; such features could be used in image processing
operations such as denoising and compression, as well as in pattern recognition.
PMID- 11014669
TI - Diffusion and innovation rates for multidimensional neuronal data with large
spatial covariances.
AB - The diffusion model has been introduced as a statistical model for processing
multidimensional neuronal data. This paper extends estimation procedures for the
parameters of this model when spatial covariances are large. The new method is
based upon linear regression techniques. It is applied to an optical recording of
the auditory cortex of a guinea pig stimulated with pure tone bursts (frequency
14 kHz).
PMID- 11014670
TI - Effects of delay on the type and velocity of travelling pulses in neuronal
networks with spatially decaying connectivity.
AB - We study a one-dimensional model of integrate-and-fire neurons that are allowed
to fire only one spike, and are coupled by excitatory synapses with delay. At
small delay values, this model describes a disinhibited cortical slice. At large
delay values, the model is a reduction of a model of thalamic networks composed
of excitatory and inhibitory neurons, in which the excitatory neurons show the
post-inhibitory rebound mechanism. The velocity and stability of propagating
continuous pulses are calculated analytically. Two pulses with different
velocities exist if the synaptic coupling is larger than a minimal value; the
pulse with the lower velocity is always unstable. Above a certain critical value
of the constant delay, continuous pulses lose stability via a Hopf bifurcation,
and lurching pulses emerge. The parameter regime for which lurching occurs is
strongly affected by the synaptic footprint (connectivity) shape. A bistable
regime, in which both continuous and lurching pulses can propagate. may occur
with square or Gaussian footprint shapes but not with an exponential footprint
shape. A perturbation calculation is used in order to calculate the spatial
lurching period and the velocity of lurching pulses at large delay values. For
strong synaptic coupling, the velocity of the lurching pulse is governed by the
tail of the synaptic footprint shape. Moreover, the velocities of continuous and
lurching pulses have the same functional dependencies on the strength of the
synaptic coupling strength gsyn: they increase logarithmically with gsyn for an
exponential footprint shape, they scale like (In gsyn)1/2 for a Gaussian
footprint shape, and they are bounded for a square footprint shape or any shape
with a finite support. We find analytically how the axonal propagation velocity
reduces the velocity of continuous pulses; it does not affect the critical delay.
We conclude that the differences in velocity and shape between the front of
thalamic spindle waves in vitro and cortical paroxysmal discharges stem from
their different effective delays.
PMID- 11014671
TI - Optic nerve evaluation among optometrists.
AB - PURPOSE: To determine agreement among optometrists regarding assessment of optic
nerve C/D ratios and perceived glaucomatous damage and to separately analyze
these results on the basis of residency training, practice setting, and glaucoma
patient experience. METHODS: Fifty-six optometrists from various modes of
professional practice evaluated 33 stereoscopic optic nerve photographs.
Observers were asked to estimate the vertical cup-to-disk (C/D) ratio and
determine the glaucomatous status of the optic nerve. The mean vertical C/D
ratio, percentage perceived as glaucomatous, and levels of interobserver and
intraobserver agreement (kappa) are reported. RESULTS: Estimated C/D ratios
differ significantly on the basis of training (p = 0.02) practice setting (p =
0.001), glaucoma patient experience (p = 0.001). Glaucomatous damage
interpretation was significantly different (p = 0.006) based upon an
optometrist's practice setting. Interobserver agreement regarding C/D ratios is
significantly higher among optometrists who have completed a residency (kappaw =
0.59) and practice in clinical settings (optometry school/medical
center/hospital) (kappaw = 0.59) compared with non-residency-trained optometrists
(kappaw = 0.52) and those practicing in commercial settings (kappaw = 0.54).
Interobserver agreement of glaucomatous damage is significantly higher among
optometrists who have completed a residency (kappa = 0.50) compared with non
residency-trained optometrists (kappa = 0.42). CONCLUSIONS: Intraobserver
agreement is higher than interobserver agreement among optometrists when C/D
ratios are estimated and the glaucomatous status of the optic nerve is assessed.
Optic nerve evaluation among optometrists is significantly influenced by
residency training, practice setting, and glaucoma patient encounters.
PMID- 11014672
TI - Field expansion for homonymous hemianopia by optically induced peripheral
exotropia.
AB - PURPOSE: To describe a novel method for prism correction of hemianopia that
provides field-of-view expansion in a convenient and functional format and to
evaluate initial clinical application. METHOD: To expand the upper quadrant of
the field, a high power prism segment (30-40delta) is placed base-out across the
upper part of the spectacle lens, on the side of the loss, at about the level of
the limbus. A similar prism segment at the lower part of the lens is used to
treat the lower field. The peripheral location of the prisms causes peripheral
exotropia. As a result a scene segment as high as the vertical span of the prism
is shifted laterally by 15 to 20 degrees relative to the view of the other eye.
At the edge of the hemianopic field loss, objects that would fall in the scotoma
of one eye are seen through the prism in the other eye, providing a simultaneous
awareness of details within the otherwise absent field-of-view. An approach for
fitting the system to patients with abnormal binocular vision (strabismus and
amblyopia, with or without diplopia) is discussed as well. The effect of the
prisms was evaluated in a noncomparative case series (12 patients). RESULTS: The
field expansion is provided at any position of lateral gaze, including gaze away
from the side of the scotoma. The effect of this technique on field expansion was
demonstrated using standard binocular perimetry. Most patients reported
substantial improvement in function and in obstacle avoidance. CONCLUSION: A
novel method for the optical treatment of hemianopia was developed and tested. It
was found to be effective in expanding the field and helping patients' mobility.
PMID- 11014673
TI - Temporal variations in myopia progression in Singaporean children within an
academic year.
AB - PURPOSE: Excessive nearwork is believed to be associated with myopia development
and progression. To investigate this further, we studied refractive error changes
and their correlation with nearwork in a cohort of grade school children in
Singapore. METHODS: Cycloplegic autorefraction was performed 5 times over 10
months on 168 children aged 7, 9, and 12 years who were further divided into
myopic and nonmyopic subgroups based in their initial refractive errors.
Information about nearwork was obtained through diaries filled out over 24 h at
the commencement of the study. RESULTS: Myopia progression was high (overall
mean: -0.87 D per year) and largely linear throughout the year, but significantly
higher rates were seen after the final school examinations in 7-year-old myopes
and nonmyopes. Overall, myopic groups exhibited higher progression rates than
nonmyopic groups, although 33.6% of subjects from the latter groups had become
myopic by the end of the study. Nearwork scores derived from the diaries were
generally not well correlated with overall myopia progression. CONCLUSIONS: The
tendency for myopia progression rates to increase after the final school
examinations in 7-year-olds is interpreted as a delayed effect of the intense
nearwork associated with preparing for them. The timing of nearwork-diary data
collection at the beginning of the study could be responsible for the poor
correlation between these data and overall myopia progression rates.
PMID- 11014674
TI - Inter-rater and intra-rater reliability in the interpretation of MTI
Photoscreener photographs of Native American preschool children.
AB - PURPOSE: To evaluate inter- and intra-rater reliability for the interpretation of
MTI Photoscreener photographs taken in a population of Native American preschool
children with a high prevalence of astigmatism. METHODS: Photographs of 369
children were rated by 11 nonexpert and 3 expert raters. Photographs for each
child were scored as pass, refer, or retake. Nonexpert raters scored photos on
two separate occasions, permitting analysis of intra-rater reliability. RESULTS:
Analyses of pass/refer responses only: inter-rater reliability was moderate to
substantial among nonexpert raters and substantial among expert raters. Intra
rater reliability among nonexperts was substantial. Analyses of all responses
(pass, refer, and retake): inter-rater reliability for pass and refer scores was
moderate among nonexperts and substantial among experts; for retake scores inter
rater reliability was slight for nonexperts and moderate for experts. Intra-rater
reliability among nonexperts was substantial for pass and refer scores and
moderate for retake scores. CONCLUSIONS: In this population with a high
prevalence of astigmatism, whether MTI photoscreening results are interpretable
is much more variable among and within raters than whether an interpretable
photograph should be scored as pass or refer. The level of agreement among raters
in the current study was influenced by the experience of the raters. In addition,
nonexpert raters were more likely to deem a photograph uninterpretable than
expert raters.
PMID- 11014675
TI - The accuracy and precision performance of four videokeratoscopes in measuring
test surfaces.
AB - In this study we evaluated the accuracy and precision of three placido-disk
videokeratoscopes (the Keratron, Medmont and TMS) and one videokeratoscope that
uses the raster-stereogrammetry technique (PAR-CTS) in elevation topography with
six test surfaces. The test surfaces were a sphere, an asphere, a multicurve, and
three bicurve surfaces. Each instrument performed well on certain test surfaces,
but none of the instruments excelled on all of the surfaces. The results showed
high accuracy of the Keratron and Medmont instruments in measuring the sphere,
asphere, and multicurve surfaces, but not the bicurve surfaces. The precision of
the Keratron and Medmont instruments were high. The TMS and PAR-CTS instruments
showed poorer accuracy than the Keratron and Medmont instruments for the
multicurve test surface but showed better performance for the bicurve surfaces.
The PAR-CTS had the poorest performance in precision of the four instruments. The
use of the Noryl spherical test surface instead of polymethyl methacrylate (PMMA)
resulted in small differences in the accuracy performance of the placido-disk
videokeratoscopes only.
PMID- 11014676
TI - Performance on the three-point Vernier alignment or acuity test as a function of
age: measurement extended to ages 5 to 9 years.
AB - The three-point Vernier alignment (or acuity) test was conducted on children from
5 to 9 years old. There is a significant difference between the 5-9 year old
subjects and those in age groups 10 to 19 and 20 to 29 years in Vernier
performance. These data were also compared with previously published data from
older subjects (up to age 70). We conclude that Vernier function has not fully
matured within the age range of 5 to 9 years; this finding is consistent with
previous results reported in the literature.
PMID- 11014677
TI - Heart and lung support interaction--modeling and simulation.
AB - Mechanical support of the lungs used to preserve life or during any kind of
surgery may have an adverse effect on the cardiovascular system. Usually,
positive pressure in alveoli diminishes lung perfusion, venous return and cardiac
output. Positive pressure during the respiratory cycle is transfered into the
thoracic space. The aim of this study was to assess how synchronization of the
respirator with spontaneous breathing influences the distribution of pressure and
ventilation in nonhomogeneous lungs and how it should influence hemodynamics. For
this purpose a multicompartmental model of respiratory system mechanics was used
in the electrical analog of a respirator-lung circuit, which enabled us to
simultaneously simulate ventilatory support and spontaneous breathing. Mechanical
properties of the respiratory system were modeled by lumped parameters:
resistances and capacitances of constant values, independent of lung volume or
inspiratory flow changes. A multicompartmental model of the respiratory system
enabled us to simulate lung pathology characterized by non-homogeneity of the
mechanical properties of the different parts of the lungs. The results of
simulations presented in the paper enable us to conclude that lung volume
increase, independent of the respirator-patient breathing synchronization, may be
modeled as the increase in pulmonary vascular resistance and alveolar pressure
increase, dependent on respirator-patient breathing synchronization, may be
averaged by esophageous balloon measurements which show intrathoracic pressure
changes.
PMID- 11014678
TI - Surface pitting of heart valve disks tested in an accelerated fatigue tester.
AB - There are various reports on the fracture of mechanical heart valves implanted in
humans or animals and it has been pointed out that fractures are induced by
erosion of the disk surface due to cavitation bubbles. Cavitation erosion on
mechanical heart valves was studied using our originally designed accelerated
fatigue tester. Several valve housings with different compliance values were
used. The number and position of pits on the valve disk were measured using an
optical microscope. Disk-closing velocity was measured and cavitation bubbles
were monitored by a high-speed video camera. It was found that disk-closing
velocity increased and cavitation erosion was enhanced with an increase in
compliance of the valve holder. Therefore, careful attention should be paid to
the compliance of an accelerated fatigue tester.
PMID- 11014679
TI - Artificial ventilation of the lungs for emergencies.
AB - The necessity for extraordinary ventilatory support may appear in different
places all over the world in cases of a massive disaster (industrial or natural),
connected with gas poisoning on a huge scale. Hospitals equipped with limited
number of respirators, adequate for peacetime activity, are not able to meet
suddenly multiplied requirements for ventilatory support. This paper describes a
preliminary study to develop a convenient, reliable method of performing
artificial ventilation of at least two patient by means of only one ventilator.
We developed a unique, new control system (patent pending) which, when placed
between a respirator and endotracheal tubes of the patients, divides the total
tidal volume between the patients' lungs and controls pressures at their airways.
A special arrangement of valves in the control system enables us to separate
inspiratory and expiratory paths for each patient and to avoid cross-infection.
The model study performed, according to ISO standards, on mechanical test lungs
has shown that the proposed control system enables us to adjust ventilatory
parameters at desired values, when lung compliance or respiratory airway
resistance differ. The proposed one-source artificial ventilation is a simple
solution to provide ventilatory support when the number of patients is greater
than the number of respirators that are available.
PMID- 11014680
TI - Oximetric and capnometric studies--aspects of natural and artificial ventilation.
AB - Methods and instrumentation of own design and their application to the
measurement of oxygen and CO2 content in blood and respiration gases are
discussed. Spectrophotometry, particularly double wavelength colorimetry using
red light and IR light, applied to the measurement of oxygen blood saturation for
in vitro examination and through an intravascular catheter for invasive in vivo
study and by means of pulse oximetry for non-invasive in vivo examination are
presented. The electrochemical methods applied to in vitro and in vivo
measurement of oxygen in blood (amperometric method) and in respiration gases
(amperometric and fuel cell methods) are discussed. The electrochemical Stow
Severinghaus method of CO2 tension measurement in blood and CO2 partial pressure
in respiratory gases as well as the selective IR light (4.26 microm) absorption
method and instruments of own design for CO2 measurements in respiratory gases
are also discussed. The methods and instrumentation described are very important
for monitoring respiratory and circulatory function, particularly during
artificial ventilation and circulatory support.
PMID- 11014681
TI - Three methods for investigating, assessing and supporting the normal and
pathological gait and manipulation activity.
AB - Three methods to describe biped locomotion as well as manipulation activity are
presented. Methods using so-called couple oscillators as rhythm generators are
described. Based on a mathematical model, results of computer simulation of biped
locomotion are presented. An indices method of assessing human gait for both
normal and pathological cases was proposed and tested. The results showed that it
is relatively easy to distinguish different gaits by using this method. This
method was tested in clinical conditions. The third method deals with the problem
of supporting the lost function of prehension movements. Implanted stimulators on
the nerves combined with external orthoses were used. The clinical results show
that these methods have practical advantages.
PMID- 11014682
TI - Computer-aided generation of stimulation data and model identification for
functional electrical stimulation (FES) control of lower extremities.
AB - Standard stimulation data for unassisted standing up of paraplegic patients was
generated by dynamic optimization linked with model simulation, to overcome the
difficulties in the present electromyogram (EMG)-based method. The generated
stimulation data were roughly in agreement with the normal subjects' EMG. From
these, it is suggested that the 'model-based' method is useful as an alternative
of the 'EMG-based method'. The same technique can be applied to generation of
patient-specific stimulation data once the musculoskeletal system of a patient is
properly identified. The musculoskeletal system must be identified from data
taken from simple and noninvasive experiments for the identification method to be
practically acceptable. We developed a musculoskeletal model and systematic
identification protocols for this purpose. They were validated for the vastus
lateralis muscle at the knee joint. The identification was successful and the
predicted joint angle trajectories closely matched the experimental data. This
implies that the model-based generation of patient-specific stimulation data is
possible.
PMID- 11014683
TI - Manifestation of internal organs malfunction by laser Doppler study on
microcirculation.
AB - Monitoring of microvascular blood perfusion provides very specific information on
the proper function or malfunction of some internal organs, e.g. the pancreas and
kidney. The laser Doppler method was used to measure microperfusion in the skin
of the lower limb of diabetic patients and patients undergoing hemodialysis. This
method offers non-invasive, real-time monitoring and is already accepted in many
clinical experiments. The method and the laser Doppler instruments used are
described. Special attention is paid to the investigation of microvascular
abnormality in diabetes by using a multichannel laser Doppler system during
postocclusive reactive hyperemia. The study group consisted of 41 diabetes and 24
healthy subjects with no history of family diabetes. The most valuable data were
obtained from the probe located on the most distal part of the foot. Some
hyperemic parameters (maximum of hyperemic response, time to peak flow) were
significantly different for the diabetic group as comparing to the norm. In the
microcirculation study during hemodialysis, three patients with kidney
dysfunction were investigated. Increase in red blood cell velocity was observed,
probably caused by better distribution of blood to the peripheral circulation.
PMID- 11014684
TI - Unconstrained physiological monotoring in daily living for health care.
AB - This paper deals with the recent development of two types of non-invasive
physiological monitoring systems for possible application in an unconstrained
manner to normal subjects for health care as well as to patients and/or
outpatients with disorders or with life support systems (artificial organs and
organ transplantations). One is an ambulatory monitoring system which allows
automatic acquisition of blood pressure, cardiac output and other cardiovascular
hemodynamic parameters on a beat-by-beat basis using the volume-compensation and
transthoracic electrical admittance method. The other is a home monitoring system
installed in a lavatory which can measure body and excreta weight together with
the ballistocardiogram as an index of cardiac ejecting function in an unaware
fashion without attachment of any sensors to the subject's body and without
special operations for measurement during toilet use. Outlines of these two
systems and monitoring results of laboratory and field testings are presented,
and these suggest that the ambulatory and non-conscious physiological monitoring
techniques described herein appear promising as a valuable and helpful means for
use in research as well as in the practical field of health monitoring at home
during daily living.
PMID- 11014685
TI - Acquisition of long-term cardiac signals for chronodiagnostic utility.
AB - Periodical and long-term examination of the cardiac function is important for
detecting early-stage disorders, and contributing to chronodiagnosis and
chronotherapeutics. Frequent or daily examination utilizing the present test
procedures, however, places the patient under stress even when it is administered
at home and not during a hospital visit. In order to cope with this issue,
monitoring systems whereby a patient is not aware of being examined were
developed taking the electrocardiogram (ECG) as an example. The ECG was monitored
while the patient was taking a bath or sleeping in bed. The system did not
utilize any body surface electrodes but introduced in-water electrodes in the
bath and textile electrodes on the bed. These systems made long-term observation
feasible without imposing any stress on the patient.
PMID- 11014686
TI - Dialyzer reuse: what we know and what we don't know.
AB - Despite extensive clinical experience, the effects of different reuse procedures
have not been fully evaluated. The available data suggest that the effect of
reuse on dialyzer performance depends upon the type of chemicals employed, the
membrane type, and the size of the solute whose removal is being assessed. The
effect of reuse on urea clearance is essentially defined by the residual cell
volume with a total cell volume of > 80% associated with a dialyzer clearance
that is within 10% of its original value. The effect of reuse on large solute
clearance can be dramatic, with the procedure resulting in substantial changes in
the beta2-microglobulin clearance of different dialyzers. Of note is the limited
data available regarding the effect of reuse procedures on dialyzers processed
more than 20 times.
PMID- 11014687
TI - Are parathyroidectomies still appropriate in chronic dialysis patients?
AB - The uremic milieu generates chronic stimulatory input to the parathyroid glands,
which is mediated principally by low calcium, high phosphate and low calcitriol,
and results in increased parathyroid hormone (PTH) synthesis and release and an
increase in parathyroid mitotic activity with the development of monoclonal areas
of nodular hyperplasia. Such glands do not fully express the machinery required
to mediate the suppressive inputs to the parathyroids; the extracellular calcium
receptor (CaR) and the vitamin D receptor (VDR) are both downregulated. In most
of these patients ablation, by parathyroidectomy or ethanol injection, provides
the only means of correcting the hyperparathyroidism; apoptosis in parathyroid
cells is negligible and clinically irrelevant. In practice, surgery is often
delayed by a doomed and ultimately futile attempt to effect control by medical
means. Better predictors of the likely success or failure of optimal non surgical
management are needed. Gland size exceeding 1 cm3 and elevated PTH despite
hypercalcemia (implying loss of suppressibility by calcium), in the presence of
good phosphate control and adequate calcitriol provision point strongly to
eventual failure of medical treatment and the need for parathyroid ablation.
Parathyroidectomy, usually subtotal, remains the standard management, with
ultrasound guided injection of ethanol or calcitriol showing promise in some
centers. The above scenario is unlikely to be changed greatly by the new emerging
vitamin D metabolites, but calcimimetic agents may well increase the scope of non
surgical management.
PMID- 11014688
TI - Non-dialytic treatment of acute hyperkalemia in the dialysis patient.
AB - Acute hyperkalemia occurs commonly amongst patients with chronic renal failure
and is especially common in noncompliant individuals. These patients often
present to the emergency room with weakness. This editorial addresses the issue
of non-dialytic treatment of hyperkalemia. Is emergency dialysis indicated in
every case? In my opinion, acute dialysis can often be delayed until the
hospital's dialysis unit opens for "regular working hours."
PMID- 11014689
TI - Does reuse have clinically important effects on dialyzer function?
PMID- 11014690
TI - Strategy for maximizing the use of arteriovenous fistulae.
AB - Increasing the use of arteriovenous fistulae in dialysis patients requires a
specific strategy. In order to properly select patients for an arteriovenous
fistula (AVF), it is essential that the nephrologist become knowledgeable about
the subject and that an organized approach be followed. Both the arterial and
venous systems must be evaluated. Evaluation of medical history, general physical
examination, specific physical examination related to the vasculature of the
extremity, vein mapping and duplex ultrasound studies are all important. It is
very important to assess the size of the vessels involved. Although a newly
created AVF should be allowed to fully mature prior to use, failure to develop
should be evaluated early. Many cases of early failure can be successfully
salvaged. Even if the patient has an arteriovenous graft, they should be
evaluated at the time of every graft failure for the possibilities of creating a
secondary AVF.
PMID- 11014691
TI - Peritoneal sclerosis: one or two nosological entities?
AB - The frequency, pathology, animal models, pathogenesis, clinical manifestations,
diagnostic criteria, therapy and prevention of peritoneal sclerosis are reviewed.
Many of these aspects have a bimodal configuration which suggests that peritoneal
sclerosis, usually considered a single pathology in peritoneal dialysis, is
actually two distinct nosological entities: simple sclerosis and sclerosing
peritonitis. The former is very frequent, with minor anatomical alterations and
low clinical impact; it is reproducible in animals by means of peritoneal
dialysis, and is clearly due to the poor biocompatibility of peritoneal dialysis
solutions. The latter is rare, with radical anatomical alterations and high
mortality requiring valid methods of diagnosis, therapy and prevention; it can
only be reproduced in animal models by means other than peritoneal dialysis and
seems to be due to factors both related and unrelated to peritoneal dialysis.
PMID- 11014692
TI - Hemodialyzer membranes and configurations: a historical perspective.
AB - The principle of hemodialysis (HD) was first described over a century ago while
the first human HD treatment was performed in 1923 with collodion tubes. Since
that time, a variety of different hemodialyzer configurations and membranes have
been used. The purpose of this article is to provide a historical review of these
various configurations and membranes. The rotating drum, coil, parallel flow, and
hollow fiber artificial kidneys are discussed. Emphasis is placed on the factors
that have influenced the shaping of the contemporary HD market.
PMID- 11014693
TI - Upper limb ischemia after vascular access surgery: differential diagnosis and
management.
AB - Hand ischemia following placement of upper limb arteriovenous accesses for
dialysis may result in debilitating complications and contribute to morbidity and
mortality on dialysis. Two distinct clinical variants of hand ischemia are
recognized: vascular steal syndrome, in which a spectrum of severity of ischemic
changes affect all tissues of the hand; and ischemic monomelic neuropathy, where
ischemia is confined to the nerves of the hand. Early diagnosis and treatment of
these complications (often including closure of the access) is imperative to
prevent hand paralysis, and digital or hand amputation.
PMID- 11014694
TI - Clinical and economic outcomes of the use of expanded criteria donors in renal
transplantation.
PMID- 11014695
TI - Comorbidity assessment in hemodialysis and peritoneal dialysis using the index of
coexistent disease.
AB - The purpose of this paper is to describe the ICED, summarize outcomes of prior
studies in which it was used, and describe the adaptations that have lead to the
present instrument. We will then demonstrate its use in quantifying the burden of
comorbid conditions in a sample of hemodialysis and peritoneal dialysis patients
from our center, and show the relationship between ICED levels and outcomes in
peritoneal dialysis patients.
PMID- 11014696
TI - Chloramine-induced methemoglobinemia in a hemodialysis patient.
PMID- 11014697
TI - Acquired cystic kidney disease.
PMID- 11014698
TI - Intravenous vitamin C for erythropoietin resistance.
PMID- 11014699
TI - Safety of high venous and arterial line pressures during hemodialysis.
PMID- 11014700
TI - Causes of lability in PTH values.
PMID- 11014701
TI - Characteristics of peritonitis in HIV-positive PD patients.
PMID- 11014702
TI - Rationing dialysis: the early years.
PMID- 11014703
TI - Measured and predicted normalized peritoneal clearances.
PMID- 11014704
TI - Primary and secondary control strategies for managing health and financial stress
across adulthood.
AB - The study examined the relation among three types of control strategies
(persistence, positive reappraisals, lowering aspirations) and subjective well
being across adulthood (N = 3,490). Specifically, the authors investigated
whether age-adapted endorsement of control strategies is conducive to subjective
well-being if individuals experience health or financial stress. The results
reveal an overall enhanced reliance on control strategies in older as compared
with younger adults. In addition, persistence showed a stronger positive relation
to subjective well-being in young adulthood as compared with old age. In midlife
and old age, positive reappraisals had a stronger positive relation to subjective
well-being than persistence. Lowering aspirations was negatively related to
subjective well-being, independent of age. Age differences in the relation of
control strategies to subjective well-being were particularly salient in
individuals who faced either health or financial stress.
PMID- 11014705
TI - Personal theories, intellectual ability, and epistemological beliefs: adult age
differences in everyday reasoning biases.
AB - Age-related differences in everyday reasoning biases were explored. In each of 2
social domains, examination of theoretical beliefs and biases along 2 dimensions
of scientific reasoning, involving the law of large numbers and the evaluation of
experimental evidence, revealed that, across age groups, scientific reasoning was
used to reject evidence that contradicted prior beliefs; relatively cursory
reasoning was used to accept belief-consistent evidence. Biased reasoning was
more common among middle-aged and older adults than among young adults.
Dispositions to engage in analytic processing were negatively related to biases,
but intellectual abilities and bias were not related. The findings support a 2
process view of adult cognitive development and suggest that the tendency to rely
on heuristic information processing increases with age.
PMID- 11014706
TI - Memorizing while walking: increase in dual-task costs from young adulthood to old
age.
AB - The dual task of memorizing word lists while walking was predicted to become more
difficult with age because balance and gait are in greater need of "attentional
resources." Forty-seven young (ages 20-30 years), 45 middle-aged (40-50), and 48
old (60-70) adults were trained to criterion in a mnemonic technique and
instructed to walk quickly and accurately on 2 narrow tracks of different path
complexity. Then. participants encoded the word lists while sitting, standing, or
walking on either track; likewise, speed and accuracy of walking performance were
assessed with and without concurrent memory encoding. Dual-task costs increased
with age in both domains; relative to young adults, the effect size of the
overall increase was 0.98 standard deviation units for middle-aged and 1.47
standard deviation units for old adults. It is argued that sensory and motor
aspects of behavior are increasingly in need of cognitive control with advancing
age.
PMID- 11014707
TI - Modeling caregiver adaptation over time: the longitudinal impact of behavior
problems.
AB - Although cross-sectional research has established the link between care demands
and various indicators of caregiver adaptation, few studies have examined the
impact of care recipients' problematic behavior over time. The present analysis
determines the importance of behavior problems when predicting rates of change in
subjective stressors (role overload and role captivity) and depression. Using 4
wave longitudinal data (N = 137) on dementia caregivers, the authors fit
individual growth curve models for care demands (i.e., behavior problems,
activities of daily living dependencies, and cognitive impairment), subjective
stressors, and depression. Subsequent structural equation models found that
increases in behavior problems were most likely to predict increases in role
overload. The findings emphasize the deleterious long-term impact of behavior
problems on individuals' emotional adaptation to caregiving.
PMID- 11014708
TI - Age differences in feeling-of-knowing and confidence judgements as a function of
knowledge domain.
AB - For two semantic knowledge domains, general and computer-related, feeling-of
knowing (FOK) and confidence level (CL) ratings and their relative accuracy were
assessed in young, middle-aged, and older adults, after test difficulty was
equated across age groups. Global memory self-efficacy beliefs were also assessed
for each domain. As expected, greater age was associated with poorer memory self
efficacy beliefs only in the computer domain. The oldest two groups were found to
be more underconfident than young adults when rating their FOK but not their CL,
for computer items but not for general items. Statistical control of age
differences in memory self-efficacy beliefs in the relevant domain greatly
reduced this age effect on computer-related FOK ratings. This finding suggests
that absolute FOK judgments are more closely related to memory self-efficacy
beliefs than are CL judgments. Gamma correlations between judgments and
recognition performance revealed that all age groups were equally accurate in FOK
and in CL judgments, in both domains.
PMID- 11014709
TI - Updating knowledge about encoding strategies: a componential analysis of learning
about strategy effectiveness from task experience.
AB - Researchers have argued for age deficits in learning about the effects of
encoding strategies from task experience, partly on the basis of absolute
accuracy of metacognitive judgments. However, these findings could be attributed
to factors other than age differences in learning. Forty older and 40 younger
adults participated in 2 study-test trials in which they studied paired
associates with imagery or repetition, predicted recall for the items, attempted
recall, and postdicted recall. Recall was greater after imagery than repetition,
yet this effect was not fully reflected by predictions made on Trial 1. Although
both older and younger adults accurately postdicted recall from Trial 1, absolute
accuracy of the predictions made on Trial 2 showed little improvement. By
contrast, both age groups demonstrated increases in between-person correlations
of predictions with recall, which is inconsistent with age deficits in knowledge
updating. Thus, both older and younger adults had updated knowledge about the
relative effects of the strategies, but such updating was not evident in the
absolute accuracy of the predictions.
PMID- 11014710
TI - Unwanted thought: age differences in the correction of social judgements.
AB - This study use a false information paradigm to study age differences in the
correction of social judgments. Younger and older adults read 2 criminal reports,
with true information printed in black and false information in red. Following
the reports, all participants were asked to recommend prison terms among other
ratings. Age differences in baseline measures were also assessed by corresponding
control groups who read only true information. Compared with younger adults under
full attention, older adults under full attention and younger adults under
divided attention were reliably influenced by the nature of the false statements
(either extenuating or exacerbating the severity of the crimes). When contrasted
with their relevant control groups, older adults under full attention and younger
adults under divided attention failed to correct their social judgments. This
study lends support to a processing resource explanation for age differences in
the correction process for social judgments.
PMID- 11014711
TI - Measures of fluency as predictors of incidental memory among older adults.
AB - This study investigated fluency performance as a mediator of age-related declines
in incidental memory performance as both are thought to rely on strategic
retrieval processes. A large sample of community dwelling older adults completed
a battery of tests assessing fluency, verbal knowledge, speed of information
processing, and incidental recall. Fluency measures included initial and excluded
letter fluency and the Uses for Objects Test, and they were assumed to reflect
increasing reliance on strategic retrieval search. Speed emerged as the best
mediator of age-related variance in incidental recall, and Uses for Objects Test
performance added to the variance after controlling for verbal knowledge and
speed. The results suggest that age-related decline in incidental recall is
largely due to speed and the strategic search of memory.
PMID- 11014712
TI - Cognitive complexity and cognitive-affective integration: related or separate
domains of adult development?
AB - This study used a latent variable approach to describe two broad domains of adult
development and their interrelations. One domain was cognitive complexity,
defined by crystallized intelligence, fluid intelligence, and reflective
cognition: the other domain was cognitive-affective integration, operationalized
in terms of integrated and defensive coping. It was hypothesized that these 2
domains are related to each other and that they imply different developmental
correlates. Structural relations among the latent variables supported a model in
which integrated coping showed positive relations with crystallized intelligence
and reflective cognition, whereas defensive coping showed negative relations to
these cognitive factors. Age and education were significant predictors of the
cognitive complexity factors, whereas evaluations of the climate in one's current
family and family of origin were related to the factors of cognitive-affective
integration.
PMID- 11014713
TI - Longitudinal changes in the contribution of genetic and environmental influences
to symptoms of depression in older male twins.
AB - Genetically informative longitudinal data on self-reported symptoms of depression
allow for an investigation of the causes of stability and change in depression
symptoms throughout adult life. In this report, the authors investigated the
relative contribution of genetic and environmental influences to symptoms of
depression in 83 monozygotic and 84 dizygotic male twin pairs from the National
Heart, Lung, and Blood Institute (NHLBI) Twin Study. Participants first completed
the Center for Epidemiologic Studies-Depression (CES-D) scale in 1985-1986 and
again during 1995-1997. Mean age of twins at baseline was 63 years, range 59 to
70. From cross-sectional genetic analyses we estimated the heritability of CES-D
to be 25% (95% confidence interval [CI], 11%-39%) at baseline and 55% (95% CI,
40%-71%) at follow-up. Fitting longitudinal genetic models to the two-wave data,
we found that stability of symptoms over the 10-year follow-up was due primarily
to continuity of genetic influences.
PMID- 11014714
TI - Is age-related stability of subjective well-being a paradox? Cross-sectional and
longitudinal evidence from the Berlin Aging Study.
AB - Subjective well-being is thought to remain relatively stable into old age despite
health-related losses. Age and functional health constraints were examined as
predictors of individual differences and intraindividual change in subjective
well-being, as indicated by positive and negative affect, using cross-sectional
(N = 516) and longitudinal (N = 203) samples from the Berlin Aging Study (age
range 70-103 years). In cross-sectional and longitudinal analyses, age and
functional health constraints were negatively related to positive affect but
unrelated to negative affect. Cross-sectionally, controlling for functional
health constraints reversed the direction of the relationship between age and
positive affect and produced a negative association between age and negative
affect. Findings suggest two qualifications to the average stability of overall
subjective well-being: Only some dimensions of subjective well-being remain
stable, while others decline; age per se is not a cause of decline in subjective
well-being but health constraints are.
PMID- 11014715
TI - Aging and reflective processes of working memory: binding and test load deficits.
AB - It was hypothesized that age-related deficits in episodic memory for feature
combinations (e.g., B. L. Chalfonte & M. K. Johnson, 1996) signal, in part,
decrements in the efficacy of reflective component processes (e.g., M. K.
Johnson, 1992) that support the short-term maintenance and manipulation of
information during encoding (e.g., F. 1. M. Craik. R. G. Morris. & M. L. Gick,
1990; T. A. Salthouse, 1990). Consistent with this, age-related binding deficits
in a working memory task were found in 2 experiments. Evidence for an age-related
test load deficit was also found: Older adults had greater difficulty than young
adults when tested on 2 features rather than 1, even when binding was not
required. Thus, disruption of source memory in older adults may involve deficits
in both encoding processes (binding deficits) and monitoring processes
(difficulty accessing multiple features, evaluating them, or both).
PMID- 11014716
TI - Target selection difficulty, negative priming, and aging.
AB - It has been recently suggested that the presence of identity negative priming
effects in old adults could occur when there is substantial processing of the
distracting information in a selective attention task (J. M. Kieley & A. A.
Hartley, 1997). In three experiments, using a letter identification task, it was
found that making target selection more difficult increased the magnitude of the
negative priming effect to a similar extent in both young and old adults.
Moreover, the size of the negative priming effect did not differ between young
and elderly participants. These results are discussed with respect to the issue
of age-related deficits in the mechanisms underlying negative priming.
PMID- 11014717
TI - Instance-based automaticity and aging: acquisition, reacquisition, and long-term
retention.
AB - This research examined age differences in the acquisition and reacquisition of
instance-based automaticity. In 2 experiments, young and older adults were
trained to enumerate targets presented in otherwise empty displays or in displays
that contained distractors. Experiment 1 revealed that older adults required more
practice to reach asymptote than young adults. For both age groups, modifications
of the identities and locations of targets produced substantial disruptions in
performance, whereas modifications of the identities or locations of distractors
produced little interference. However, no age differences in the representations
of instances in memory were obtained in participants who reached asymptote.
Experiment 2 revealed age deficits in the long-term retention and rate of
reacquisition of instance-based automaticity 18 months after initial training.
PMID- 11014718
TI - Dose-response evaluation of the therapeutic index for inhaled budesonide in
patients with mild-to-moderate asthma.
AB - PURPOSE: Inhaled corticosteroids have beneficial effects on pulmonary function
and inflammation in patients with asthma, but they also cause systemic adverse
effects, such as adrenal suppression. We evaluated the therapeutic index of
inhaled corticosteroids in asthmatic patients by comparing their dose-response
effects on lung function, surrogate markers of airway inflammation, and tests of
adrenal function. SUBJECTS AND METHODS: After a 10-day placebo run-in, we
evaluated the effects of 200 microg, 400 microg, and 800 microg of inhaled
budesonide, each dose given twice daily sequentially for 3 weeks in 26 patients,
aged 35 +/- 12 years (mean +/- SD), with mild-to-moderate asthma. Measurements
were made of bronchial reactivity, exhaled nitric oxide (a marker of airway
inflammation), spirometry, serum eosinophilic cationic protein concentration, and
10-hour overnight urinary cortisol excretion. Plasma cortisol levels were
measured at 8 AM and after stimulation with human corticotropin releasing factor.
RESULTS: For measurements of pulmonary function and exhaled nitric oxide, there
was a plateau in the mean response to budesonide between 400 microg (low dose)
and 800 microg (medium dose) per day, whereas for eosinophilic cationic protein
and bronchial challenge, maximal benefits occurred between 800 and 1,600 microg
(high dose) per day. Effects on plasma cortisol levels showed maximal suppression
at 1,600 microg of budesonide per day. The proportion of patients with an optimal
therapeutic index, in terms of a good airway response (fourfold decrease in
bronchial hyperreactivity) and minimal systemic response (overnight urinary
cortisol greater than 20 nmol), was similar at low-dose (46%) and at high-dose
(52%) budesonide. The proportion of patients with a suboptimal therapeutic index,
a good airway response with a marked systemic response (overnight urinary
cortisol greater than 20 nmol), increased from 4% at low dose to 38% at high
dose. CONCLUSIONS: In patients with mild-to-moderate atopic asthma, there were
dose-related effects of budesonide on surrogate markers of inflammation
(bronchial hyperreactivity and serum eosinophilic cationic protein), although
higher doses were associated with adrenal suppression and a decrease in the
therapeutic index.
PMID- 11014719
TI - Ginkgo biloba extract for the treatment of intermittent claudication: a meta
analysis of randomized trials.
AB - PURPOSE: The optimal treatment of intermittent claudication has not yet been
identified. Ginkgo biloba extract has been reported to have beneficial effects.
We performed a meta-analysis of the efficacy of Ginkgo biloba extract for
intermittent claudication based on the results of randomized, placebo-controlled,
double-blind trials. METHODS: Literature searches of MEDLINE, EMBASE, BIOSIS,
AMED, CISCOM, and the Cochrane Library were performed to identify studies on the
topic. Manufacturers of commercial Ginkgo biloba products and authors of original
publications and reviews were contacted to provide additional information. No
language restrictions were imposed. RESULTS: Eight randomized, placebo
controlled, double-blind trials were included. Meta-analysis found a significant
difference in the increase in pain-free walking distance in favor of Ginkgo
biloba (weighted mean difference: 34 meters, 95% confidence interval [CI]: 26 to
43 meters). In studies using similar methodological features (ergometer speed: 3
km/h, inclination: 12%) this difference was 33 meters in favor of Ginkgo biloba
(95% CI: 22 to 43 meters). Adverse effects were rare, mild, and transient.
CONCLUSIONS: These results suggest that Ginkgo biloba extract is superior to
placebo in the symptomatic treatment of intermittent claudication. However, the
size of the overall treatment effect is modest and of uncertain clinical
relevance.
PMID- 11014720
TI - A multicenter, randomized trial of fluconazole versus amphotericin B for empiric
antifungal therapy of febrile neutropenic patients with cancer.
AB - PURPOSE: To compare the efficacy and safety of fluconazole and amphotericin B as
empiric antifungal therapy of febrile neutropenic patients with cancer. PATIENTS
AND METHODS: A total of 317 neutropenic patients (<500 cells/mm3) with persistent
or recrudescent fever despite 4 or more days of antibacterial therapy were
randomly assigned to receive either fluconazole (400 mg intravenously once daily)
or amphotericin B (0.5 mg/kg once daily). Patients were evaluated for the
efficacy and safety of each drug by clinical criteria, frequent cultures and
radiological procedures, and laboratory values. A response was classified as
satisfactory at the end of therapy if the patient was afebrile, had no clinical
or microbiological evidence of fungal infection, and did not require study
termination due to lack of efficacy, drug toxicity, or death. RESULTS: A
satisfactory response occurred in 68% of the patients treated with fluconazole
(107 of 158 patients) and in 67% of patients treated with amphotericin B (106 of
159 patients). Progressive or new fungal infections during therapy occurred in 13
(8%) patients treated with fluconazole (8 with Candida, 5 with Aspergillus) and
in 10 (6%) patients treated with amphotericin B (5 with Candida, 3 with
Aspergillus, 2 with other fungi). Adverse events related to study drug
(especially fever, chills, renal insufficiency, electrolyte disturbances, and
respiratory distress) occurred more often in patients treated with amphotericin B
(128 [81%] of 159 patients) than patients treated with fluconazole (20 [13%] of
158 patients, P = 0.001). Eleven (7%) patients treated with amphotericin B but
only 1 (1%) patient treated with fluconazole were terminated from the study owing
to an adverse event (P = 0.005). Overall mortality (27 [17%] patients treated
with fluconazole versus 34 [21%] patients treated with amphotericin B) and
mortality from fungal infection (7 [4%] patients treated with fluconazole versus
5 [3%] patients treated with amphotericin B) were similar in each study group.
CONCLUSIONS: Intravenous fluconazole can be an effective and safe alternative to
amphotericin B for empiric antifungal therapy in many febrile neutropenic
patients. However, because fluconazole may be ineffective in the treatment of
Aspergillus, patients at risk for that infection should be evaluated by chest
radiograph, computed tomographic scanning, and cultures before the use of empiric
fluconazole therapy.
PMID- 11014721
TI - An outbreak of Legionella micdadei pneumonia in transplant patients: evaluation,
molecular epidemiology, and control.
AB - PURPOSE: To describe a nosocomial outbreak of Legionella micdadei pneumonia in
transplant patients and to characterize the source of the outbreak and the
control measures utilized. SUBJECTS AND METHODS: We performed retrospective
Legionella micdadei serologic testing to enhance case finding in transplant
patients with pneumonia that lacked a documented microbial etiology, as well as
prospective environmental surveillance of water sites and testing for Legionella
in clinical specimens. RESULTS: During a 3-month period, 12 cases of Legionella
micdadei pneumonia were identified either by culture or serologic testing among
38 renal and cardiac transplant patients. Legionella micdadei isolates from hot
water sources were found by pulsed-field gel electrophoresis to have a DNA
banding pattern that was identical to the isolates from the first 3 culture
positive cases and from 2 cases that occurred 16 months later. CONCLUSIONS:
Hospitals caring for organ transplant recipients and other immunosuppressed
patients must be aware of the possibility of environmental sources of outbreaks
of Legionella infection. A first-line screen with the Legionella urine antigen
test will identify Legionella pneumophila serogroup 1. However, specific cultures
in outbreak situations should be considered to identify other Legionella
pneumophila serotypes and the nonpneumophila Legionella species.
PMID- 11014722
TI - Osteomalacia due to vitamin D depletion: a neglected consequence of intestinal
malabsorption.
AB - PURPOSE: Osteomalacia due to vitamin D depletion is believed to be rare in the
United States because of the routine fortification of milk and other dairy
products with vitamin D. We present a series of patients with histologically
verified osteomalacia due to vitamin D depletion to emphasize the need for more
careful and systematic surveillance of patients at risk of this metabolic bone
disease. METHODS: Between 1989 and 1994, 17 patients with osteomalacia due to
vitamin D depletion were seen in the Bone and Mineral Division of Henry Ford
Health System, Detroit. All patients had a transiliac bone biopsy after in vivo
double tetracycline labeling. Biochemical indexes of vitamin D nutritional
status, parathyroid function, markers of bone turnover, and bone mineral density
were assessed at the time of bone biopsy. The duration of symptoms, the lag
between the cause of vitamin D depletion and the development of symptoms, and the
radiologic findings were recorded. RESULTS: Osteomalacia was suspected by the
referring physician in only 4 of the 17 patients, although a gastrointestinal
disorder that can lead to vitamin D depletion was present in every patient.
Thirteen of the patients had sustained at least one osteoporotic fracture (wrist,
spine, or hip), and most had low appendicular and axial bone mineral density. All
patients had one or more biochemical abnormalities consistent with vitamin D
depletion. In 4 patients, a progressive rise in the serum alkaline phosphatase
level was recorded but was not investigated until the patient presented with bone
pain, muscle weakness, or fracture. CONCLUSIONS: Osteomalacia due to vitamin D
depletion appears not to be suspected or diagnosed promptly in susceptible
patients, perhaps because their physicians were not sufficiently aware of this
condition.
PMID- 11014723
TI - A meta-analysis of the Papanicolaou smear and wet mount for the diagnosis of
vaginal trichomoniasis.
AB - PURPOSE: To obtain reliable estimates of the sensitivity and specificity of the
cervical Papanicolaou (Pap) smear and wet mount to diagnose vaginal
trichomoniasis. METHODS: Articles indexed in MEDLINE (1976-1998) about diagnostic
tests for trichomoniasis and their listed references were retrieved. Thirty
studies (9,501 patients) that used trichomonas culture as a gold standard were
selected. Studies were defined as level I if they fulfilled at least two of the
following three criteria: consecutive patients were evaluated prospectively, the
decision to culture was not influenced by test results, and there was independent
and blind comparison with culture. Studies were classified as level II if one
criterion was fulfilled, and as level III otherwise. RESULTS: The pooled
sensitivity of the Pap smear for the diagnosis of trichomoniasis among level I
studies was 57% (95% confidence interval [CI]: 51% to 63%) and the pooled
specificity was 97% (95% CI: 93% to 100%). The likelihood ratio for a positive
Pap smear was 19 among level I studies (range: 8 to 62). The pooled sensitivity
of the wet mount among level I studies was 58% (95% CI: 51% to 66%); among level
II studies, the sensitivity was 72% (95% CI: 62% to 81%), and among level III
studies, the sensitivity was 82% (95% CI: 67% to 97%). The overall specificity of
the wet mount was 99.8%. CONCLUSIONS: A positive Pap smear for trichomonads in
settings in which trichomoniasis is common (prevalence > or =20%) requires
treatment. A positive Pap smear is indeterminate when the prevalence of
trichomoniasis is about 10%; thus, clinicians should either confirm the diagnosis
by culture or treat all such patients, recognizing that some patients will be
treated unnecessarily. A culture should be obtained in women with a positive Pap
smear who are unlikely to have trichomoniasis (prevalence < or =1%). While a
positive wet mount is diagnostic, a negative wet mount does not exclude
trichomoniasis.
PMID- 11014724
TI - Ischemic complications after percutaneous transluminal coronary angioplasty.
AB - The ischemic complications ofpercutaneous transluminal coronary angioplasty
(PTCA) include abrupt closure, which occurs in 2% to 10% of patients and is
associated with increased morbidity and mortality. Periprocedural myocardial
infarction due to side branch occlusion or embolization of platelet aggregates or
thrombus occurs in 5% to 20% of patients. Patients with acute coronary syndromes,
older age, and complex lesions are at greater risk of periprocedural
complications. Technical advances, primarily stenting, are useful in the
prevention and management of acute closure, but are also accompanied by
thrombotic complications. It remains to be seen whether the new antithrombin
agents reduce the rate of periprocedural complications if used in combination
with aspirin and new antiplatelet therapies. These new antiplatelet agents
(ticlopidine, clopidogrel, abciximab, eptifibatide, and tirofiban) reduce the
rate of ischemic complications and have become standard adjunctive therapy for
patients who undergo PTCA.
PMID- 11014725
TI - Apoptosis and neurologic disease.
AB - Many neurological disorders involve cell death. During development of the nervous
system, cell death is a normal feature. Elimination of substantial numbers of
initially generated cells enables useful pruning of "mismatched" or excessive
cells produced by exuberance during the proliferative and migratory phases of
development. Such cell death, occurring by "programmed" pathways, is termed
apoptosis. In mature organisms, cells die in two major fashions, either by
necrosis or apoptosis. In the adult nervous system, because there is little cell
production during adulthood, there is little normal cell death. However,
neurological disease is often associated with significant neural cell death.
Acute disorders, occurring over minutes to hours, such as brain trauma,
infarction, hemorrhage, or infection, prominently involve cell death, much of
which is by necrosis. Chronic disorders, with relatively slow central nervous
system degeneration, may occur over years or decades, but may involve cell
losses. Such disorders include motor neuron diseases such as amyotrophic lateral
sclerosis (ALS), cerebral dementing disorders such as Alzheimer's disease and
frontotemporal dementia, and a variety of degenerative movement disorders
including Parkinson's disease, Huntington's disease, and the inherited ataxias.
There is evidence that the mechanism of neuronal cell death in these disorders
may involve apoptosis. Direct conclusive evidence of apoptosis is scarce in these
chronic disorders, because of the swiftness of cell death in relation to the
slowness of the disease. Thus, at any particular time point of assessment, very
few cells would be expected to be undergoing death. However, it is clearly of
importance to define the type of cell death in these disorders. Of significance
is that while treating the underlying causes of these conditions is an admirable
goal, it may also be possible to develop productive therapies based on
alleviating the process of cell death. This is particularly likely if this cell
loss is through apoptosis, a programmed process for which the molecular cascade
is increasingly understood. This article reviews our understanding of apoptosis
in the nervous system, concentrating on its possible roles in chronic
neurodegenerative disorders.
PMID- 11014726
TI - Accuracy and cost-effectiveness of single-view echocardiographic screening for
suspected mitral valve prolapse.
PMID- 11014727
TI - Supine exercise capacity identifies patients at low risk for perioperative
cardiovascular events and predicts long-term survival.
PMID- 11014728
TI - Inhaled corticosteroid therapy for asthma: therapeutic and toxic potentials.
PMID- 11014729
TI - Ginkgo biloba: a living fossil.
PMID- 11014730
TI - Management of persistent fever in the neutropenic patient.
PMID- 11014731
TI - Nosocomial Legionella micdadei infection in transplant patients: fortune favors
the prepared mind.
PMID- 11014732
TI - Increased use of beta-blockers after acute myocardial infarction.
PMID- 11014733
TI - Hepatitis C and B-cell non-Hodgkin's lymphoma: a geographically variable
association?
PMID- 11014734
TI - Fatal rhabdomyolysis associated with simvastatin in a renal transplant patient.
PMID- 11014735
TI - Fatal ventricular fibrillation during a low-dose dobutamine stress test.
PMID- 11014737
TI - Managed care and education: seizing the opportunities.
PMID- 11014736
TI - Minocycline-induced systemic adverse reaction with liver and bone marrow
granulomas and Sezary-like cells.
PMID- 11014738
TI - The past as prologue to the future: the times, they've been a-changin'.
PMID- 11014739
TI - Developmental psychopathology: concepts and challenges.
AB - The defining features of developmental psychopathology concepts include attention
to the understanding of causal processes, appreciation of the role of
developmental mechanisms, and consideration of continuities and discontinuities
between normality and psychopathology. Accomplishments with respect to these
issues are reviewed in relation to attachment disorders, antisocial behavior,
autism, depressive disorder, schizophrenia, and intellectual development. Major
research challenges remain in relation to measurement issues, comorbidity, gender
differences, cognitive processing, nature-nurture interplay, heterotypic
continuity, continuities between normal variations and disorders, developmental
programming, and therapeutic mechanisms in effective treatments.
PMID- 11014740
TI - Developmental systems and psychopathology.
AB - Efforts to understand the etiology of adult mental disorders by studying children
has produced unanticipated changes in our understanding of pathology, individual
development, and the role of social context. Among these are the blurring of the
division between mental illness and mental health, the need to attend to patterns
of adaptation rather than personality traits, and the powerful influences of the
social world on individual development. Current developmental views place
deviancy in the dynamic relation between individuals and their contexts. At
another level, when we view the history of developmental psychopathology,
dialectical developmental processes are evident as we trace how patterns of
adaptation of researchers, expressed in theoretical models and empirical
paradigms. increasingly have come to match the complexities of human mental
health and illness.
PMID- 11014741
TI - Experience in the midst of variation: new horizons for development and
psychopathology.
AB - This essay explores implications of current trends in developmental science for
understanding psychopathology at the dawn of the new millennium. Over the past
half century, it has become clear that uniform and general principles of
development (i.e., those that are applicable at all times, to all people, and in
all places) will be of limited utility in understanding the processes of greatest
interest in development and psychopathology. Instead, such processes are
characterized by complexly organized individuals engaged in developmental
transactions within multiple contexts (ranging from the biological environment of
neurons to the cultural systems of meaning that shape people's lives). These
transactions in turn often yield variable outcomes. In order to portray how we
have come to this conclusion, we first provide a view of contemporary research in
three areas of early development: the biology of the developing brain, the
complexities of early emotional development, and the cultural contexts of child
development. We then trace how an increasing appreciation of organized
complexity, developmental transactions, and the meaning of context have played
out in the emerging field of infant mental health before closing with our vision
of new opportunities for the study of experience in the midst of variation.
PMID- 11014742
TI - Cultural influences on developmental processes and outcomes: implications for the
study of development and psychopathology.
AB - The purpose of this paper is to trace the role of culture as an explanatory
construct in developmental processes and outcomes, and its implications in the
understanding of developmental psychopathology. Literature reviews were conducted
by historical period: 1930-1939, 1960-1969, and 1990-1999. The percentage of the
total articles and chapters pertaining to cultural issues increased as a function
of time. Both conceptual and methodological continuities and discontinuities were
observed among the three periods. The preponderance of comparative studies using
deficit models still remains, but more enlightened alternative conceptual models,
within culture studies, and measures of cultural processes, are emerging. In
contrast, although contextual influences are considered important in
developmental psychopathology, the field lags in its empirical consideration of
cultural influences. The need to seriously address these issues will increase as
globalization and rapid cultural change become even more the norm than the
exception.
PMID- 11014744
TI - Psychosocial influences: critiques, findings, and research needs.
AB - Nongenetic factors have a major influence on psychopathology. Knowledge on
specific psychosocial risk and protective mechanisms is more limited because of
inadequate attention to measurement issues, person effects on the environment,
and the possibility of genetic mediation. Nevertheless, a range of research
strategies may be used to provide rigorous tests of causal hypotheses; these have
shown the importance of environmentally mediated risks. Challenges for the future
include greater use of such research strategies, improved measures of
psychosocial risks that can be applied to large samples, investigation of origins
of risks, identification of causes of time trends in levels of psychopathology,
delineation of psychosocial effects on lifetime liability, understanding of
environmental effects on the organism, appreciation of processes involved in
developmental programming, and understanding of individual differences in
susceptibility.
PMID- 11014743
TI - The interplay of genetic influences and social processes in developmental theory:
specific mechanisms are coming into view.
AB - In the coming years we can look forward to research that clarifies specific
mechanisms that account for the interplay between genetic and environmental
influences on psychological development. Certain misconceptions, arising from
research traditions initiated by Francis Galton on the one hand and G. Stanley
Hall on the other, may now be set aside in the light of new evidence. Three
important findings promise a new synthesis. First, while each of us is born with
about 100,000 genes that, under ordinary circumstances, do not change, the
expression of these genes on behavior is dynamic. Some genetic influences are
expressed early in development, but others are manifest many years later. Second,
genetic factors often account not only for some of the individual differences in
the measures of adjustments we typically use to monitor development but also for
individual differences in environmental experiences that covary with those
measures of adjustment. Indeed, genetic factors have been found to account for a
surprising amount of covariance between measures of the social environment and of
adjustment in young children, adolescents, and adults. Third, the expression of
genetic influences are very malleable and responsive to the social environment.
These new findings are revealing specific mechanisms for the interplay of genetic
and social environmental factors in four domains. First, the social environment
may play both a necessary and specific role in the expression of particular
genetic influences on a range of behaviors from depression to social
responsibility. Second, an understanding of the interplay between the social
environment and genetics may lead to a clearer definition of the phenotypic
manifestations of particular genetic influences. Third, we will-as a result of
these studies-have a clearer fix on the timing of important events and their
sequence in development. Fourth, this new genre of work promises to illumine more
completely mechanisms by which the social environment influences development
independent of genetic influence.
PMID- 11014745
TI - The place of psychodynamic theory in developmental psychopathology.
AB - Psychoanalysis ushered in this century. Will its influence on developmental
psychopathology end in the next? The paper explores some critical obstacles in
the way of psychodynamic research, including the fragmentation of psychoanalytic
theory. the relative independence of theory from its clinical and empirical base,
the predominance of inductive scientific logic, the polymorphous use of terms,
the privacy of clinical data, the dominance of the reconstructionist stance, and
the isolation of psychoanalysis from psychology and neurobiology. Notwithstanding
these limitations, core psychoanalytic precepts are not only consistent with some
of the most important advances of the last decade but may also be helpful in
elaborating these new discoveries in the next century. Psychoanalysis is centered
on the notion that complex, conflicting, unconscious representations of mental
states constitute a key facet of normal and abnormal development. This notion
retains its power, and deserves a prominent position among the major frames of
reference to guide developmental science in the next century.
PMID- 11014746
TI - Developing mechanisms of self-regulation.
AB - Child development involves both reactive and self-regulatory mechanisms that
children develop in conjunction with social norms. A half-century of research has
uncovered aspects of the physical basis of attentional networks that produce
regulation, and has given us some knowledge of how the social environment may
alter them. In this paper, we discuss six forms of developmental plasticity
related to aspects of attention. We then focus on effortful or executive aspects
of attention, reviewing research on temperamental individual differences and
important pathways to normal and pathological development. Pathologies of
development may arise when regulatory and reactive systems fail to reach the
balance that allows for both self-expression and socially acceptable behavior. It
remains a challenge for our society during the next millennium to obtain the
information necessary to design systems that allow a successful balance to be
realized by the largest possible number of children.
PMID- 11014747
TI - Internalizing problems of childhood and adolescence: prospects, pitfalls, and
progress in understanding the development of anxiety and depression.
AB - The focus of this article is on internalizing problems that are experienced by
children and adolescents. We provide an historical perspective, selectively
examine the current state of knowledge, consider advances and gaps in what is
known, and identify new research directions. Diagnosis, epidemiology, theory, and
research first are considered separately for anxiety and depressive disorders.
These internalizing problems, however, whether clinical or subclinical, share
many common features and show high comorbidity rates. We emphasize the importance
of systematic analysis of comorbid anxiety and depression, including their
comorbidity with externalizing problems. This could lead to more valid
classification of subtypes of internalizing problems and further an understanding
of the diverse conditions that constitute internalized distress. We highlight the
need to study anxiety and depression within a developmental psychopathology
framework, as well as to include both categorical and dimensional assessments of
these problems in the same research designs. This will be essential for
understanding the complex interplay of biological and environmental processes
that contribute to the emergence, progression, and amelioration of internalizing
problems over time.
PMID- 11014748
TI - Early externalizing behavior problems: toddlers and preschoolers at risk for
later maladjustment.
AB - The early emergence and developmental implications of externalizing behavior
problems in toddlers and preschoolers are discussed with an emphasis on which
young children are truly at risk for continuing problems. The extant literature
is reviewed with a focus on the stability of early externalizing behavior and the
diverse pathways that young children, primarily boys, with early-emerging
problems may follow. Findings from a number of studies, both epidemiological and
high risk, suggest that the small subgroup of boys with multiple risk factors
that include especially high levels of early hyperactivity and aggression, and
high levels of negative parenting and family stress, are most likely to evidence
continuing problems at school entry. Sociodemographic and neighborhood influences
are also discussed, as are implications for future research and policy.
PMID- 11014749
TI - Is asperger syndrome/high-functioning autism necessarily a disability?
AB - This article considers whether Asperger syndrome (AS) or high-functioning autism
(HFA) necessarily leads to disability or whether AS/HFA simply leads to
"difference." It concludes that the term "difference" in relation to AS/ HFA is a
more neutral, value-free, and fairer description than terms such as "impairment,"
"deficiency," or "disability"; that the term "disability" only applies to the
lower functioning cases of autism; but that the term "disability" may need to be
retained for ASIHFA as long as the legal framework provides financial and other
support only for individuals with a disability. Two models are summarized which
attempt to define in what way individuals with AS/HFA are "different": the
central coherence model, and the folk psychology-folk physics model. The
challenge for research is to test the value of such models and to precisely
characterize the differences in cognitive style.
PMID- 11014750
TI - The neurodevelopmental hypothesis of schizophrenia: following a trail of evidence
from cradle to grave.
AB - This is a critical review of the literature related to the neurodevelopmental
hypothesis of schizophrenia which posits that the illness is related to abnormal
brain development. The review focuses on data deriving from clinical studies, and
it is organized according to the life phase from which the data were collected:
conception and birth, infancy and childhood up to the onset of the illness, after
illness onset, and postmortem. The neurodevelopmental hypothesis is supported by
several pieces of evidence, including increased frequency of obstetric
complications in patients with schizophrenia: the presence of minor physical
anomalies; the presence of neurological, cognitive, and behavioral dysfunction
long before illness onset; a course and outcome of the illness itself that is
incompatible in most cases with a degenerative illness; the stability of brain
structural measures over time; and the absence of postmortem evidence of
neurodegeneration. A historical perspective on how this research accumulated and
a section addressing important areas of future investigation are also provided.
We conclude that schizophrenia is certainly not a degenerative brain disorder,
and that it is likely that a brain insult in utero or at birth plays a role in
its expression. Current evidence cannot completely exclude the role of
environmental variables after birth. In addition, it is possible that other
psychiatric disorders may also have a neurodevelopmental component.
PMID- 11014751
TI - Integrating competence and psychopathology: pathways toward a comprehensive
science of adaptation in development.
AB - This paper examines the conceptual and empirical connections between competence
and psychopathology, two historically rich traditions for the study of adaptation
in development, and what might be gained from their integration. Historical roots
of these two traditions are reviewed, then overlaps in their definition are
considered, with a focus on the ways in which judgments about competence enter
into the nosology of mental disorders. DSM-IV is analyzed from the perspective of
competence, and the debate about "harmful dysfunction" in defining mental
disorder is discussed in relation to competence. Different models explaining the
empirical associations of competence and psychopathology are delineated, and
illustrative empirical evidence is provided. Potential explanations include
confounded concepts and methods, symptoms undermining the effectiveness of
adaptation in the environment, failures in age-salient developmental tasks
leading to emotional and behavioral problems, transactional influences, shared
vulnerability or risk factors producing both kinds of difficulties, and more
complex models. The potential benefits of integrating competence and
psychopathology as two major approaches to adaptation are discussed in regard to
theory, classification of mental disorder, research, and intervention.
PMID- 11014752
TI - Behavioural implications of alarm mistrust as a function of task workload.
AB - The research was conducted to investigate the effect of increasing primary task
and alarm workload on alarm mistrust as reflected by alarm and primary task
performances. A total of 126 undergraduate students performed a complex
psychomotor task battery three times, with the number of concurrent tasks
increasing each time. During their performance, the students were required to
react to an alarm system (including visual and auditory components) of
questionable reliability. Depending on the group to which participants were
assigned, the alarm presentation rate constituted a low-, medium- or high
workload condition. Alarm response data (times, frequencies, accuracies) and
primary task data (tracking error) were analyzed to assess performance
differences as a function of primary and secondary task workload levels. Results
generally supported the hypotheses: increasing primary task and alarm task
workload degraded alarm response performance. Also, response frequencies
supported earlier research suggesting that participants 'probability match' their
response rates to alarm system reliability. The results are discussed with regard
to the cry-wolf effect, attention theory and alarm system design.
PMID- 11014753
TI - Analysis of 3-D human foot forms using the Free Form Deformation method and its
application in grading shoe lasts.
AB - An effective way to design well-fitting products is to analyse human body forms
and to classify them into several groups. In the present study, a new method is
proposed to analyse human body forms using the FFD (Free Form Deformation)
technique. The FFD method is a way to deform the shapes of object smoothly by
moving control lattice points set around the object. The reference body form is
automatically deformed to coincide with the other body forms using the FFD
method. The dissimilarity is defined by the movements of the control lattice
points. The foot forms of 56 Japanese adult females were analysed with this
method, and distributions for them were calculated using multi-dimensional
scaling. The first axis contrasts feet with high dorsal arches and low dorsal
arches, and the second axis is related to the antero-posterior proportion of the
foot. As an application of the present method, a last of width EEEE was designed
from an existing last of width E by applying the control lattice points that
converted a representative foot of width E into a foot of width EEEE. The new
EEEE width last reflected the allometric differences between narrow and wide feet
better than one obtained by a conventional method. It was found that the present
method with FFD is not only useful for classifying 3-D human body forms, but also
has potential as applications for designing well-fitting products.
PMID- 11014754
TI - A three-dimensional dynamic posture prediction model for simulating in-vehicle
seated reaching movements: development and validation.
AB - A three-dimensional dynamic posture prediction model for simulating in-vehicle
seated reaching movements is presented. The model employs a four-segment 7
degrees-of-freedom linkage structure to represent the torso, clavicle and right
upper extremity. It relies on an optimization-based differential inverse
kinematics approach to estimate a set of four weighting parameters that quantify
a time-constant, inter-segment motion apportionment strategy. In the development
phase, 100 seated reaching movements performed by 10 subjects towards five
typical in-vehicle targets were modelled, resulting in 100 sets of weighting
parameters. Statistical analysis was then conducted to relate these parameters to
target and individual attributes. In the validation phase, the generalized model,
with parameter values statistically synthesized, was applied to novel data sets
containing 700 different reaching movements (towards different targets and/or by
different subjects). The results demonstrated the model's ability to generate
close representations in prediction: the overall mean time-averaged error in
joint angle was 5.2 degrees, and the median was 4.7 degrees, excluding reaches
towards two extreme targets (for which modelling errors were excessive). The
model's general success in prediction and its unique characteristics led to
implications with regard to the performance and underlying control strategies of
human reaching movements.
PMID- 11014755
TI - Kinetic changes associated with load carriage using two rucksack designs.
AB - This study assessed changes in kinetics from unloaded walking associated with
load carriage using both a traditional and a new rucksack design that
incorporates front balance pockets (AARN). Nine subjects walked at 3(+/-0.05) km
x h(-1) over a force plate unloaded and carrying 25.6 kg in each of the
rucksacks. The order of trials was randomized and speed-controlled by use of
photoelectric cells and a millisecond timer. Anteroposterior and vertical ground
reaction forces were analyzed using repeated measures ANCOVA (speed covariate).
There was a trend for the AARN pack to elicit a shorter support time than the
traditional pack, 1.025+/-0.049 versus 1.037+/-0.06 s (p = 0.056), while the
unloaded condition produced the shortest support time, 1.016+/-0.04 s. Both
braking and propulsive forces for the rucksacks were significantly greater than
for unloaded walking. While there was no significant difference between the packs
for the braking force, the AARN pack produced a significantly lower (p<0.05)
propulsive force than the traditional rucksack, 0.79+/-0.2 versus 0.94+/-0.16 N x
kg bodyweight(-1). Both rucksacks produced significantly greater (p<0.001)
vertical force peaks than unloaded walking, the increases being proportional to
the increase in system weight. These findings indicate that there may be some
advantage in terms of propulsive force production for the front/back system.
PMID- 11014756
TI - After-effects of the common cold on mood and performance.
AB - The present study examined whether volunteers who had recently had common colds
showed impairments in mood and performance in the weeks following the illness.
All volunteers (n = 24) were tested when healthy to provide baseline data for
simple and choice reaction time tasks, attention and memory tasks and ratings of
mood. When participants developed a cold (n = 13) they returned to the laboratory
so that the illness could be verified. When they were symptom free they returned
to the laboratory and repeated the procedure. They then completed the study with
a final session 1 week later. Volunteers (n = 11) who remained healthy over 10
weeks were recalled as controls and also repeated the procedures. The results
showed that those who had recently had colds showed few impairments in mental
performance and mood. Taken together with the results of previous studies, this
suggests that after-effects of viral infection are largely restricted to severe
illnesses such as infectious mononucleosis and influenza. After-effects of colds
may occur but these probably reflect poor learning at the time of the illness.
PMID- 11014757
TI - Cardiorespiratory and thermoregulatory response of working in fire-fighter
protective clothing in a temperate environment.
AB - The cardiorespiratory and thermal responses of two intensities of treadmill
exercise were compared for brief periods (12 min) in fire ensemble (FE) but
without self contained breathing apparatus, and sports ensemble (SE), in a
temperature environment. A further experiment explored the responses of subjects
exercising in FE over a prolonged period (60 min). Eighteen male fire-fighters
wearing either FE or SE walked on a level treadmill for 6 min at 5 km x h(-1)
increasing to 7 km x h(-1) for 6 min. Following a recovery interval of 1 h, the
exercise protocol was repeated in the second ensemble; the order of ensemble was
balanced. Heart rate (HR), rectal temperature (Tre), VO2 max and rating of
perceived exertion (RPE) were monitored continuously under both ensembles. At 7
km x h(-1), VO2 was significantly higher (p<0.05) in FE (36.1 and 39.9 ml x kg(
1) x min(-1)) than in SE and represented 74% VO2 max. There were no changes Tre.
In experiment 2, following a rest interval of at least 36 h, eight subjects in FE
walked on the treadmill at 6 km x h (gradient 10%) for 60 min also in temperate
conditions, where HR, Tre and RPE were recorded at 10-min intervals. During the
60-min exercise in FE, HR reached 161 beats x min(-1) and Tre increased to 38.3
degrees C. Despite considerable subject discomfort, Tre remained below dangerous
levels (38.4 degrees C). When RPE were compared with a physiological strain index
(PSI) calculated from Tre and HR data over 60 min, there was no significant
difference (p<0.05) with a correlation coefficient (r) of 0.98. The results
suggest that RPE and PSI are closely related when exercise is sufficiently
prolonged or intense to elevate Tre and HR in fire-fighters wearing FE in
temperate conditions. If further investigation confirms this relationship for hot
humid conditions in which fire-fighters operate, then with training, it may
provide individuals with a valid measure of dangerous levels of perceived heat
strain.
PMID- 11014758
TI - Behavioural compensation by drivers of a simulator when using a vision
enhancement system.
AB - Technological progress is suggesting dramatic changes to the tasks of the driver,
with the general aim of making driving environment safer. Before any of these
technologies are implemented, empirical research is required to establish if
these devices do, in fact, bring about the anticipated improvements. Initially,
at least, simulated driving environments offer a means of conducting this
research. The study reported here concentrates on the application of a vision
enhancement (VE) system within the risk homeostasis paradigm. It was anticipated,
in line with risk homeostasis theory, that drivers would compensate for the
reduction in risk by increasing speed. The results support the hypothesis
although, after a simulated failure of the VE system, drivers did reduce their
speed due to reduced confidence in the reliability of the system.
PMID- 11014759
TI - Fault management in supervisory control: the effect of false alarms and support.
AB - Automation has changed the role of human operators from direct manual control to
supervision. Their main task is to monitor whether system performance remains
within pre-specified ranges and intervention is only required in unusual
situations. One of the consequences is a loss of situation awareness, which
significantly affects performance in abnormal, time-critical situation. The
present study reports two experiments, both dealing with fault management in a
maritime supervisory control task. The first experiment investigated to what
extent false alarms would affect performance and diagnosis behaviour when
multiple disturbances occurred. Thirty-nine students from maritime curricula
diagnosed disturbances that could either be real or turn out to be a false alarm.
The presence of false alarms not only affected the rate with which the subsystems
under control were sampled, but it also increased problem-solving time. One of
the reasons for suboptimal performance in dealing with fault propagation was
tunnel vision: participants had a tendency to deal with disturbances
sequentially. In the second experiment the effect of support on performance and
diagnosis behaviour was investigated. Two types of support were distinguished:
interactive support requiring participants to provide the symptom values and
automatic support that directly provided the correct action. Thirty students from
maritime curricula diagnosed disturbances with the help of either the interactive
or the noninteractive support tool. The results indicated that even though both
support tools gave the same advice on how to act, more incorrect actions were
taken in the non-interactive support condition. Even though no differences in
performance were found after the tool had been removed, it was shown that
participants who were used to interactive support used a more structured problem
solving strategy than participants used to the non-interactive support.
Consequences for system design are discussed.
PMID- 11014760
TI - Maximum reach envelope for the seated and standing male and female for industrial
workstation design.
AB - Maximum reach envelopes for the 5th, 50th and 95th percentile reach lengths of
males and females in seated and standing work positions were determined. The use
of a computerized potentiometric measurement system permitted functional reach
measurement in 15 min for each subject. The measurement system captured reach
endpoints in a dynamic mode while the subjects were describing their maximum
reach envelopes. An unbiased estimate of the true reach distances was made
through a systematic computerized data averaging process. The maximum reach
envelope for the standing position was significantly (p<0.05) larger than the
corresponding measure in the seated position for both the males and females. The
average reach length of the female was 13.5% smaller than that for the
corresponding male. Potential applications of this research include designs of
industrial workstations, equipment, tools and products.
PMID- 11014762
TI - Use of accelerometers as an ergonomic assessment method for arm acceleration-a
large-scale field trial.
AB - Ergonomists need easy-to-use, quantitative job evaluation methods to assess risk
factors for upper extremity work-related musculoskeletal disorders in field-based
epidemiology studies. One device that may provide an objective measure of
exposure to arm acceleration is a wrist-worn accelerometer or activity monitor. A
field trial was conducted to evaluate the performance of a single-axis
accelerometer using an industrial population (n=158) known to have diverse upper
limb motion characteristics. The second phase of the field trial involved an
examination of the relationship between more traditional observation-based
ergonomic exposure measures and the monitor output among a group of assembly-line
production employees (n=48) performing work tasks with highly stereotypic upper
limb motion patterns. As expected, the linear acceleration data obtained from the
activity monitor showed statistically significant differences between three
occupational groups known observationally to have different upper limb motion
requirements. Among the assembly-line production employees who performed
different short-cycle assembly work tasks, statistically significant differences
were also observed. Several observation-based ergonomic exposure measures were
found to explain differences in the acceleration measure among the production
employees who performed different jobs: hand and arm motion speed, use of the
hand as a hammer, and, negatively, resisting forearm rotation from the torque of
a power tool. The activity monitors were found to be easy to use and non
intrusive, and to be able to distinguish arm acceleration among groups with
diverse upper limb motion characteristics as well as between different assembly
job tasks where arm monitors were performed repeatedly at a fixed rate.
PMID- 11014761
TI - Experimental investigation and biomechanical analysis of lower limb movements for
clutch pedal operation.
AB - Lower limb movements for clutch-pedal operations were investigated and the
influence of four parameters (seat height, pedal travel, pedal travel
inclination, pedal resistance) was studied using a multi-adjustable experimental
seat. Fifteen subjects participated in the experiment: five short females, five
average height males and five tall males. A biomechanical model has been proposed
to explain how pedal force direction could be controlled. The experimental
observations show that the lower limb movement of clutch pedal operation is
mainly guided by the geometric constraints imposed by the task and its
environment, especially during the depression phase. The results support the
hypothesis that movements obey the principle of minimum work and minimum
discomfort. Furthermore, it seems that a functional segmentation exists between
the distal joint (ankle) and the proximal joints (knee and hip), thus simplifying
the control problem, which is due to the redundancy of the human body. It appears
that the depression movement is controlled by proprioceptive feedback related to
foot displacement and pedal force, from the fact that the deceleration duration
during the depression phase increases with the pedal resistance and pedal travel.
The minimum pedal resistance and pedal travel are discussed.
PMID- 11014763
TI - Transition from Journal of Diarrhoeal Diseases Research to Journal of Health,
Population and Nutrition.
PMID- 11014764
TI - Rotavirus serotypes: classification and importance in epidemiology, immunity, and
vaccine development.
AB - The development and implementation of safe and effective vaccines to prevent the
enormous health burden of rotavirus-associated disease is a global public health
goal. Human rotaviruses, the major aetiological agents of severe infantile
diarrhoea worldwide, display surprisingly diverse and complex serotypic
specificities. Ten VP7 serotypes and 7 VP4 serotypes have so far been detected.
An increasing number of observations, obtained from analyses of (i) natural
rotavirus infections in infants and young children, (ii) experimental rotavirus
infections in laboratory animals, and (iii) extensive rotavirus vaccine field
trials performed in different populations of various parts of the world, appears
to support the concept that serotype-specific antibodies to rotaviruses play an
important role in protection against rotavirus-associated illnesses. Thus, the
first licensed rotavirus vaccine (RRV-based quadrivalent vaccine) was designed to
cover the epidemiologically important VP7 serotype 1, 2, 3, and 4.
PMID- 11014765
TI - Prevention of diarrhoea in a poor District of Santo Domingo, Dominican Republic:
practices, knowledge, and barriers.
AB - The study, conducted in a poor periurban community of Santo Domingo, Dominican
Republic, assessed the practices, knowledge, and barriers relating to prevention
of diarrhoea. A total of 582 caregivers of children, aged less than 5 years, were
systematically sampled from four barrios. Results of the study showed that 55% of
the caregivers did not boil drinking water for children; 38% did not always wash
hands of the children prior to meals; 87% of the children did not always wear
shoes outside their house; and 54% were breastfed for less than one year.
Biomedical knowledge about these practices was high among the caregivers, and was
not related to the reported behaviours. However, several barriers were
significantly related to practices, including lapse in caregiving, limited
resources, erroneous beliefs, and non-compliance by children. Health education,
based on a biomedical knowledge-deficit model, may have little impact on
improving the diarrhoea-prevention practices in these communities. Greater
attention should, therefore, be directed toward the barriers experienced by
caregivers of children.
PMID- 11014766
TI - Identification of enteric pathogens in HIV-positive patients with diarrhoea in
northern India.
AB - Enteric pathogens associated with chronic diarrhoea in HIV-positive patients were
studied. The study was conducted during January 1995-December 1998. Stool
specimens from all diarrhoea patients (n = 26) were examined microscopically for
ova and parasites using wet preparations and stained smears. Stool samples from
diarrhoea patients were also cultured on appropriate media to isolate enteric
bacterial pathogens. Of the 59 patients, 26 (44%) had prolonged diarrhoea for
more than 4 weeks. Enteric pathogens were detected in 19 (73%) of the 26
patients: 17 patients harboured a single pathogen, and 2 patients had mixed
pathogens. The detection rate of emerging parasites, including Isospora,
Cryptosporidium, Blastocystis hominis, and Strongyloides stercoralis as a single
agent, was significantly higher than conventional pathogens (50% vs 19.2%; p <
0.05). Only one patient harboured both conventional and emerging pathogens
(Entamoeba histolytica and Cryptosporidium). Isospora belli was detected in 8
(31%) of the 26 diarrhoea patients: in 7 (27%) patients as a single agent and in
one patient with S. stercoralis. Cryptosporidium was identified in 3 (11%)
diarrhoea patients: in 2 (8%) patients as a single agent and in one patient with
E. histolytica, followed by B. hominis in 2 (8%) patients. E. histolytica was
most commonly isolated (3/26; 11.5%), followed by Giardia lamblia,
enteropathogenic Escherichia coli, and Campylobacter jejuni (one patient each).
Parasitic pathogens were frequently associated with HIV-positive patients with
diarrhoea in northern India. I. belli was the most frequent parasite isolated,
followed by Cryptosporidium. Stools of all HIV-positive patients with diarrhoea
should thoroughly be investigated to identify aetiologic agents for proper
management.
PMID- 11014767
TI - Vibrio cholerae O139 Bengal: a descriptive study.
AB - A prospective study was conducted to determine the clinical and laboratory
characteristics and the clinical course of cholera due to Vibrio cholerae O139
Bengal. The study subjects included 22 adult males with stool culture-proven V.
cholerae O139. On enrollment, mean +/- SD concentrations (mmol/L) of serum
sodium, potassium, chloride, and bicarbonate were 134 +/- 3, 4 +/- 1, 102 +/- 4,
and 13 +/- 4 respectively, and stool sodium, potassium, chloride, and bicarbonate
concentrations were 120 +/- 24, 18 +/- 6, 93 +/- 16, and 37 +/- 9 respectively.
Seventeen patients (7.8%) had faecal leukocytes ranging from 11 to 50 per high
power field. All V. cholerae O139 isolates (100%) were susceptible to
tetracycline, erythromycin, and ciprofloxacin, 92% to furazolidine, and only 5%
to trimethoprim-sulphamethaxazole. The median (interquartile) volume of liquid
stool during the first 24 hours was 9 (5-12) litre. The median (interquartile)
volume of liquid stool and the amounts of intravenous and oral rehydration fluids
required during the entire study period were 16 (9-24) litre, 9 (6-18) litre, and
14 (9-20) litre respectively. The median (interquartile) duration of diarrhoea
was 80 (48-104) hours. The median (interquartile) duration of excretion of V.
cholerae O139 in stool was 5 (3-6) days. Clinical and laboratory features, and
case management of cholera due to V. cholerae O139 are very similar to
conventional cholera due to V. cholerae O1.
PMID- 11014768
TI - Isolation and antibiotic susceptibility of Salmonella, Shigella, and
Campylobacter from acute enteric infections in Egypt.
AB - While Campylobacter, Salmonella, and Shigella remain major contributors to acute
enteric infections, few studies on these pathogens have been conducted in Egypt.
From January 1986 to December 1993, 869 Salmonella, Shigella and Campylobacter
strains were isolated from stool specimens from 6,278 patients, presenting to the
Abbassia Fever Hospital, Cairo, Egypt, with acute enteric infections. Salmonella
predominated, totalling 465 isolates, followed by Shigella with 258 isolates, and
Campylobacter with 146 isolates. Of the Shigella isolates, 124 were Shigella
flexneri, 49 were S. sonnei, 47 were S. dysenteriae (mainly serotype 1, 2, and
3), and 38 were S. boydii. Campylobacter spp. comprised 92 Campylobacter jejuni
and 54 C. coli isolates. Isolation of Salmonella was highest during the months of
February-March, June-July, and October-November, while that of Shigella was
maximal from July to October. Isolation of Campylobacter increased during May
June and again during August-October. Although Salmonella was sensitive to
amikacin, aztreonam, ceftriaxone, and nalidixic acid, it was, however, resistant
to erythromycin, streptomycin, ampicillin, chloramphenicol, and tetracycline.
Shigella (> 80%) was sensitive to amikacin, ceftriaxone, cephalothin,
sulphamethoxazole-trimethoprim (except S. sonnei), aztreonam, and nalidixic acid.
Resistance (> 50%) was noted only for ampicillin, chloramphenicol, and
tetracycline. C. jejuni and C. coli were resistant to cephalothin, aztreonam, and
streptomycin. Some of the above antibiotics were employed to characterize the
Egyptian isolates, but did not have any clinical utility in the treatment of
diarrhoea. Significant differences (p < 0.05) were observed in the resistance
profiles of Shigella and Salmonella between late 1980s and early 1990s. The
results suggest the use of fluoroquinolones or a third-generation cephalosporin
as an empirical treatment of enteric diseases. However, alternative control
strategies, including the aggressive development of broadly protective vaccines,
may be more effective approaches to curbing morbidity and mortality due to acute
enteric infections.
PMID- 11014769
TI - Serotypes and subgroups of rotavirus isolated from children in central Brazil.
AB - Group A rotavirus, obtained from children of Goiania, Brazil, during 1987-1994,
were analyzed for subgroup and G serotype by enzyme-linked immunosorbent assay
with monoclonal antibodies. The index of serotyping obtained was 61.4% with the
following proportions: G1--19.7%, G2--28.0%, G3--9.8%, G4--1.5%, and G5--2.3%. It
was observed that G1 occurred from 1987 to 1989 and from 1993 to 1994, and G2
from 1990 to 1993. About 94% of the samples (85/90) could be subgrouped with the
following results: 55.5% for SG II, 7.8% SG I, and 31.1% for SG non-I-non-II.
Unusual relationship patterns were also detected among serotypes, subgroups, and
profiles of electropherotypes in 57.0% of the samples: 20 of them were G2/SG
II/"long" profile. The results suggest that variation in temporal and regional
characteristics should be considered in the development of rotavirus vaccine.
PMID- 11014770
TI - Production of heat-labile enterotoxin by strains of Aeromonas veronii bv veronii.
AB - Three isolates of Aeromonas veronii bv veronii (2 environmental, one blood
infection) were examined to see if they produce any enterotoxin and, if so, to
determine its characteristics. Two isolates caused fluid accumulation in the
initial rabbit ileal loop tests. The other strain did so after a single passage
through the rabbit ileal loop. All the isolates showed gradual enhancement of
fluid secretion after each subsequent passage. Inocula of 1 x 10(4) viable cells
and 0.25 mL of culture filtrate caused fluid accumulation comparable to those of
toxigenic Vibrio cholerae 569B. The enterotoxic activity was inactivated at
higher temperature, and showed biological activity over a wide range of pH. The
only histopathological change observed was depletion of mucous from goblet cells.
The findings of the study indicate that strains of A. veronii bv veronii produce
a heat-labile, pH-stable diarrhoeagenic factor without causing any damage to the
intestinal mucosa.
PMID- 11014771
TI - Carbachol potentiates cholera toxin-induced secretion in a colonic epithelial
cell line (HT29-19A) and rat ileal mucosa in vitro.
AB - Recent studies show that enteric nerves are involved in the action of cholera
toxin, both in vivo and in vitro. The aim of this study was to investigate in
vitro the influence of carbachol, a cholinergic agonist, on the action of cholera
toxin. Cultured HT29-19A cell lines and rat ileal mucosa were used in an Ussing
chamber for the measurement of short-circuit current induced by cholera toxin.
Cyclic AMP was measured from HT29-19A cell lines by standard radio-immunoassay.
Pre-treatment of the HT29-19A cell lines with carbachol potentiated cholera toxin
induced secretory response, and enhanced accumulation of cAMP. Carbachol also
potentiated the cholera toxin-secretory response in the rat ileal mucosa, but
only following pretreatment with the prostaglandin synthesis inhibitor,
indomethacin. There was synergistic interaction between cholera toxin and
cholinergic neurotransmitter carbachol on the intestinal epithelium. Cholinergic
agonists may play a role in regulating the secretory response to the toxin. Such
interaction is masked in the intact tissues in vitro due to the release of
prostaglandins during isolation.
PMID- 11014772
TI - Gluten-free diet improves iron-deficiency anaemia in patients with coeliac
disease.
AB - Two cases of newly-diagnosed asymptomatic coeliac disease with 3 years of
unexplained severe iron-deficiency anaemia are presented. Oral iron
supplementation had no effect on their serum iron levels and, therefore, had no
influence on their anaemia. Upper gastrointestinal endoscopy confirmed normal
macroscopic findings. Duodenal biopsies revealed subtotal villous atrophy of the
mucosa of the small intestine. A strict gluten-free diet led to an increase in
serum iron, resolution of anaemia, and restitution of normal mucosal morphology.
Thus, severe iron-deficiency anaemia associated with asymptomatic coeliac disease
is responsible to gluten-free diet.
PMID- 11014773
TI - Antibiotic resistance conferred by conjugative plasmid in Escherichia coli
isolated from community ponds of Kathmandu Valley.
PMID- 11014774
TI - Hospitals continue to find robots helpful in foodservice delivery.
PMID- 11014775
TI - Espresso kiosks can be profitable addition to hospital foodservice.
PMID- 11014776
TI - Atkins diet helps combat diabetes.
PMID- 11014777
TI - Physicians drive cost reductions in top orthopaedic unit.
PMID- 11014778
TI - Manage patients' pain for better quality, lower costs.
PMID- 11014779
TI - System's drug guide reveals costs of branded, generic drugs.
PMID- 11014780
TI - Adopt long-stay action board to examine discharge barriers, cut unnecessary
hospital days.
PMID- 11014781
TI - Greater physician productivity tied to more RNs, support staff.
PMID- 11014782
TI - Committing to consistency cuts ventilator days, ICU costs.
PMID- 11014783
TI - X-ray quality improvement affects safety, cycle time, patient satisfaction.
PMID- 11014785
TI - System revamps ambulatory care to improve patients' experience.
PMID- 11014784
TI - Dysfunctional uterine bleeding: new treatment strategies promise lower costs,
higher quality.
PMID- 11014786
TI - Looking at charges by cost center helps build care plans.
PMID- 11014787
TI - Willingness to pay for mammography: item development and testing among five
ethnic groups.
AB - The goal of this study was to develop a willingness to pay (WTP) question for
mammography that is appropriate for low income, ethnically-diverse women. Through
qualitative research with 50 low income women of five ethnic groups we developed
both a WTP question and a willingness to travel question (WTT). After being
refined through interviews with 41 women, these questions were pilot tested on a
random sample of 52 low income, ethnically-diverse women in the San Francisco
area. Results show that the concepts underlying WTP and WTT were culturally
appropriate to the five ethnicities in this study. Analyses generally confirm the
validity of the WTP and WTT questions. As expected, WTP was associated with
household income, perceived risk of cancer, and knowledge that one needs a
mammogram even after a clinical breast examination. Despite the small samples,
WTP varied among the ethnic groups. Additionally, WTT was moderately correlated
with the natural log of WTP (r = 0.58, P < 0.001). These questions are now in use
in a larger clinical trial and future analyses will explore willingness to pay
and willingness to travel within and across the ethnic groups.
PMID- 11014788
TI - Quick action in ER improves stroke care for all patients.
PMID- 11014789
TI - Hoping for improved outcomes, Texas hospital aligns staffing for developmentally
supportive care.
AB - Take better care of fragile babies with a staff structure that encourages
bonding. Texas Children's Hospital in Houston has been making big efforts to
provide developmentally supportive care for babies since 1996. Still, neither
staff nor physicians thought nurses knew their tiny charges well enough. Texas
Children's hopes a new staffing structure will change all that. Discover the
details.
PMID- 11014791
TI - New website pools wide variety of infection control information.
PMID- 11014790
TI - Losing time finding stretchers? Indoor 'GPS' helps hospitals locate equipment,
patients.
AB - Find missing equipment fast with the indoor equivalent of the global positioning
system. Billerica, MA-based PinPoint Co. is marketing a system to locate
equipment, such as stretchers and wheelchairs, based on radio-frequency signals
emitted from tags on the equipment. A New York hospital that has used the system
says it could have a quick payback time.
PMID- 11014792
TI - Infection rates drop at hospitals participating in reporting system.
AB - Data Benchmarks: The rates of nosocomial and surgical-wound infections have
plummeted at hospitals participating in the National Nosocomial Infections
Surveillance, a voluntary program of the federal Centers for Disease Control and
Prevention. Compare your hospital's performance with the top benchmarks in a new
report and learn what organizers say are the essential components of the
program's success.
PMID- 11014793
TI - System uses pharmacists to take on medication errors.
PMID- 11014794
TI - NY system lowers incidence of pressure ulcers with new tool for assessing
patients' risk.
AB - Preventing pressure ulcers is simple--pay close attention to patients. That means
real close. North Shore-Long Island-Jewish Health System shares how it began
daily assessments of patients' risks for developing pressure injuries and reduced
the number of cases 29% and 80% in the two worst severity levels.
PMID- 11014795
TI - Secrets to process improvement revealed: prioritize and finance.
AB - To build a better process improvement program, review the processes behind it.
There's truth in that tongue-twister: Good ideas for clinical reform often
languish if hospitals don't have a structure to support them. Park Nicollet
Clinic and Methodist Hospital, an award-winning system in Minneapolis, MN, shares
its tips for advancing clinical improvement initiatives.
PMID- 11014796
TI - Intense training, monitoring helps carry clinical protocols from trials to actual
practice.
AB - Can't get a clinical protocol to work in the real world? The problem might lie in
training. Intense training and steady monitoring are the keys to getting good
results from protocols in actual clinical practice, according to the Center for
Behavioral Health in Bloomington, IN. Examining the performance of its panic
disorder program, the center found it equaled the results of clinical research
trials.
PMID- 11014797
TI - Top 100 in cardiac care perform 4.7% to 31% better than others.
AB - Data Benchmarks: Measure your hospital against the best in cardiovascular care. A
new study from HCIA-Sachs LLC shows that the top-performing cardiovascular
programs are ahead of their peers by 4.7% to 31% in eight measures of clinical
quality and efficiency.
PMID- 11014798
TI - Andre Gratia: a forerunner in microbial and viral genetics.
PMID- 11014799
TI - Long-term experimental evolution in Escherichia coli. IX. Characterization of
insertion sequence-mediated mutations and rearrangements.
AB - As part of a long-term evolution experiment, two populations of Escherichia coli
B adapted to a glucose minimal medium for 10,000 generations. In both
populations, multiple IS-associated mutations arose that then went to fixation.
We identify the affected genetic loci and characterize the molecular events that
produced nine of these mutations. All nine were IS-mediated events, including
simple insertions as well as recombination between homologous elements that
generated inversions and deletions. Sequencing DNA adjacent to the insertions
indicates that the affected genes are involved in central metabolism (knockouts
of pykF and nadR), cell wall synthesis (adjacent to the promoter of pbpA-rodA),
and ill-defined functions (knockouts of hokB-sokB and yfcU). These genes are
candidates for manipulation and competition experiments to determine whether the
mutations were beneficial or merely hitchhiked to fixation.
PMID- 11014800
TI - Saccharomyces cerevisiae BUB2 prevents mitotic exit in response to both spindle
and kinetochore damage.
AB - The spindle assembly checkpoint-mediated mitotic arrest depends on proteins that
signal the presence of one or more unattached kinetochores and prevents the onset
of anaphase in the presence of kinetochore or spindle damage. In the presence of
either damage, bub2 cells initiate a preanaphase delay but do not maintain it.
Inappropriate sister chromatid separation in nocodazole-treated bub2 cells is
prevented when mitotic exit is blocked using a conditional tem1(c) mutant,
indicating that the preanaphase failure in bub2 cells is a consequence of events
downstream of TEM1 in the mitotic exit pathway. Using a conditional bub2(tsd)
mutant, we demonstrate that the continuous presence of Bub2 protein is required
for maintaining spindle damage-induced arrest. BUB2 is not required to maintain a
DNA damage checkpoint arrest, revealing a specificity for spindle assembly
checkpoint function. In a yeast two-hybrid assay and in vitro, Bub2 protein
interacts with the septin protein Cdc3, which is essential for cytokinesis. These
data support the view that the spindle assembly checkpoint encompasses regulation
of distinct mitotic steps, including a MAD2-directed block to anaphase initiation
and a BUB2-directed block to TEM1-dependent exit.
PMID- 11014801
TI - Mutation of the ATP-binding pocket of SSA1 indicates that a functional
interaction between Ssa1p and Ydj1p is required for post-translational
translocation into the yeast endoplasmic reticulum.
AB - The translocation of proteins across the yeast ER membrane requires ATP
hydrolysis and the action of DnaK (hsp70) and DnaJ homologues. In Saccharomyces
cerevisiae the cytosolic hsp70s that promote post-translational translocation are
the products of the Ssa gene family. Ssa1p maintains secretory precursors in a
translocation-competent state and interacts with Ydj1p, a DnaJ homologue.
Although it has been proposed that Ydj1p stimulates the ATPase activity of Ssa1p
to release preproteins and engineer translocation, support for this model is
incomplete. To this end, mutations in the ATP-binding pocket of SSA1 were
constructed and examined both in vivo and in vitro. Expression of the mutant
Ssa1p's slows wild-type cell growth, is insufficient to support life in the
absence of functional Ssa1p, and results in a dominant effect on post
translational translocation. The ATPase activity of the purified mutant proteins
was not enhanced by Ydj1p and the mutant proteins could not bind an unfolded
polypeptide substrate. Our data suggest that a productive interaction between
Ssa1p and Ydj1p is required to promote protein translocation.
PMID- 11014802
TI - Glucose monitoring in fission yeast via the Gpa2 galpha, the git5 Gbeta and the
git3 putative glucose receptor.
AB - The fission yeast Schizosaccharomyces pombe responds to environmental glucose by
activating adenylate cyclase. The resulting cAMP signal activates protein kinase
A (PKA). PKA inhibits glucose starvation-induced processes, such as conjugation
and meiosis, and the transcription of the fbp1 gene that encodes the
gluconeogenic enzyme fructose-1,6-bisphosphatase. We previously identified a
collection of git genes required for glucose repression of fbp1 transcription,
including pka1/git6, encoding the PKA catalytic subunit, git2/cyr1, encoding
adenylate cyclase, and six "upstream" genes required for adenylate cyclase
activation. The git8 gene, identical to gpa2, encodes the alpha subunit of a
heterotrimeric guanine-nucleotide binding protein (Galpha) while git5 encodes a
Gbeta subunit. Multicopy suppression studies with gpa2(+) previously indicated
that S. pombe adenylate cyclase activation may resemble that of the mammalian
type II enzyme with sequential activation by Galpha followed by Gbetagamma. We
show here that an activated allele of gpa2 (gpa2(R176H), carrying a mutation in
the coding region for the GTPase domain) fully suppresses mutations in git3 and
git5, leading to a refinement in our model. We describe the cloning of git3 and
show that it encodes a putative seven-transmembrane G protein-coupled receptor. A
git3 deletion confers the same phenotypes as deletions of other components of the
PKA pathway, including a germination delay, constitutive fbp1 transcription, and
starvation-independent conjugation. Since the git3 deletion is fully suppressed
by the gpa2(R176H) allele with respect to fbp1 transcription, git3 appears to
encode a G protein-coupled glucose receptor responsible for adenylate cyclase
activation in S. pombe.
PMID- 11014804
TI - Synthetic lethal interactions suggest a role for the Saccharomyces cerevisiae
Rtf1 protein in transcription elongation.
AB - Strong evidence indicates that transcription elongation by RNA polymerase II (pol
II) is a highly regulated process. Here we present genetic results that indicate
a role for the Saccharomyces cerevisiae Rtf1 protein in transcription elongation.
A screen for synthetic lethal mutations was carried out with an rtf1 deletion
mutation to identify factors that interact with Rtf1 or regulate the same process
as Rtf1. The screen uncovered mutations in SRB5, CTK1, FCP1, and POB3. These
genes encode an Srb/mediator component, a CTD kinase, a CTD phosphatase, and a
protein involved in the regulation of transcription by chromatin structure,
respectively. All of these gene products have been directly or indirectly
implicated in transcription elongation, indicating that Rtf1 may also regulate
this process. In support of this view, we show that RTF1 functionally interacts
with genes that encode known elongation factors, including SPT4, SPT5, SPT16, and
PPR2. We also show that a deletion of RTF1 causes sensitivity to 6-azauracil and
mycophenolic acid, phenotypes correlated with a transcription elongation defect.
Collectively, our results suggest that Rtf1 may function as a novel transcription
elongation factor in yeast.
PMID- 11014803
TI - Suppressors of mdm20 in yeast identify new alleles of ACT1 and TPM1 predicted to
enhance actin-tropomyosin interactions.
AB - The actin cytoskeleton is required for many aspects of cell division in yeast,
including mitochondrial partitioning into growing buds (mitochondrial
inheritance). Yeast cells lacking MDM20 function display defects in both
mitochondrial inheritance and actin organization, specifically, a lack of visible
actin cables and enhanced sensitivity to Latrunculin A. mdm20 mutants also
exhibit a temperature-sensitive growth phenotype, which we exploited to isolate
second-site suppressor mutations. Nine dominant suppressors selected in an
mdm20/mdm20 background rescue temperature-sensitive growth defects and
mitochondrial inheritance defects and partially restore actin cables in haploid
and diploid mdm20 strains. The suppressor mutations define new alleles of ACT1
and TPM1, which encode actin and the major form of tropomyosin in yeast,
respectively. The ACT1 mutations cluster in a region of the actin protein
predicted to contact tropomyosin, suggesting that they stabilize actin cables by
enhancing actin-tropomyosin interactions. The characteristics of the mutant ACT1
and TPM1 alleles and their potential effects on protein structure and binding are
discussed.
PMID- 11014805
TI - Involvement of very short DNA tandem repeats and the influence of the RAD52 gene
on the occurrence of deletions in Saccharomyces cerevisiae.
AB - Chromosomal rearrangements, such as deletions, duplications, or Ty transposition,
are rare events. We devised a method to select for such events as Ura(+)
revertants of a particular ura2 mutant. Among 133 Ura(+) revertants, 14 were
identified as the result of a deletion in URA2. Of seven classes of deletions,
six had very short regions of identity at their junctions (from 7 to 13 bp long).
This strongly suggests a nonhomologous recombination mechanism for the formation
of these deletions. The total Ura(+) reversion rate was increased 4.2-fold in a
rad52Delta strain compared to the wild type, and the deletion rate was
significantly increased. All the deletions selected in the rad52Delta context had
microhomologies at their junctions. We propose two mechanisms to explain the
occurrence of these deletions and discuss the role of microhomology stretches in
the formation of fusion proteins.
PMID- 11014806
TI - A role for cytosolic hsp70 in yeast [PSI(+)] prion propagation and [PSI(+)] as a
cellular stress.
AB - [PSI(+)] is a prion (infectious protein) of Sup35p, a subunit of the
Saccharomyces cerevisiae translation termination factor. We isolated a dominant
allele, SSA1-21, of a gene encoding an Hsp70 chaperone that impairs [PSI(+)]
mitotic stability and weakens allosuppression caused by [PSI(+)]. While [PSI(+)]
stability is normal in strains lacking SSA1, SSA2, or both, SSA1-21 strains with
a deletion of SSA2 cannot propagate [PSI(+)]. SSA1-21 [PSI(+)] strains are
hypersensitive to curing of [PSI(+)] by guanidine-hydrochloride and partially
cured of [PSI(+)] by rapid induction of the heat-shock response but not by growth
at 37 degrees. The number of inheritable [PSI(+)] particles is significantly
reduced in SSA1-21 cells. SSA1-21 effects on [PSI(+)] appear to be independent of
Hsp104, another stress-inducible protein chaperone known to be involved in
[PSI(+)] propagation. We propose that cytosolic Hsp70 is important for the
formation of Sup35p polymers characteristic of [PSI(+)] from preexisting material
and that Ssa1-21p both lacks and interferes with this activity. We further
demonstrate that the negative effect of heat stress on [PSI(+)] phenotype
directly correlates with solubility of Sup35p and find that in wild-type strains
the presence of [PSI(+)] causes a stress that elevates basal expression of Hsp104
and SSA1.
PMID- 11014807
TI - Sequence composition and context effects on the generation and repair of
frameshift intermediates in mononucleotide runs in Saccharomyces cerevisiae.
AB - DNA polymerase slippage occurs frequently in tracts of a tandemly repeated
nucleotide, and such slippage events can be genetically detected as frameshift
mutations. In long mononucleotide runs, most frameshift intermediates are
repaired by the postreplicative mismatch repair (MMR) machinery, rather than by
the exonucleolytic proofreading activity of DNA polymerase. Although
mononucleotide runs are hotspots for polymerase slippage events, it is not known
whether the composition of a run and the surrounding context affect the frequency
of slippage or the efficiency of MMR. To address these issues, 10-nucleotide
(10N) runs were inserted into the yeast LYS2 gene to create +1 frameshift
alleles. Slippage events within these runs were detected as Lys(+) revertants.
10G or 10C runs were found to be more unstable than 10A or 10T runs, but neither
the frequency of polymerase slippage nor the overall efficiency of MMR was
greatly influenced by sequence context. Although complete elimination of MMR
activity (msh2 mutants) affected all runs similarly, analyses of reversion rates
in msh3 and msh6 mutants revealed distinct specificities of the yeast Msh2p-Msh3p
and Msh2p-Msh6p mismatch binding complexes in the repair of frameshift
intermediates in different sequence contexts.
PMID- 11014808
TI - Suppression of the profilin-deficient phenotype by the RHO2 signaling pathway in
Saccharomyces cerevisiae.
AB - Profilin plays an important role in actin organization in all eukaryotic cells
through mechanisms that are still poorly understood. We had previously shown that
Mid2p, a transmembrane protein and a potential cell wall sensor, is an effective
multicopy suppressor of the profilin-deficient phenotype in Saccharomyces
cerevisiae. To better understand the role of Mid2p in the organization of the
actin cytoskeleton, we isolated five additional multicopy suppressors of
pfy1Delta cells that are Rom1p, Rom2p, Rho2p, Smy1p, and the previously
uncharacterized protein Syp1p. The problems of caffeine and NaCl sensitivity,
growth defects at 30 degrees and 37 degrees, the accumulation of intracellular
vesicular structures, and a random budding pattern in pfy1Delta cells are
corrected by all the suppressors tested. This is accompanied by a partial
repolarization of the cortical actin patches without the formation of visible
actin cables. The overexpression of Mid2p, Rom2p, and Syp1p, but not the
overexpression of Rho2p and Smy1p, results in an abnormally thick cell wall in
wild-type and pfy1Delta cells. Since none of the suppressors, except Rho2p, can
correct the phenotype of the pfy1-111/rho2Delta strain, we propose a model in
which the suppressors act through the Rho2p signaling pathway to repolarize
cortical actin patches.
PMID- 11014809
TI - Spore-killing meiotic drive factors in a natural population of the fungus
Podospora anserina.
AB - In fungi, meiotic drive is observed as spore killing. In the secondarily
homothallic ascomycete Podospora anserina it is characterized by the abortion of
two of the four spores in the ascus. We have identified seven different types of
meiotic drive elements (Spore killers). Among 99 isolates from nature, six of
these meiotic drive elements occurred in a local population. Spore killers
comprise 23% of the natural population of P. anserina in Wageningen, The
Netherlands, sampled from 1991 to 1997. One Spore-killer type was also found in a
French strain dating from 1937. All other isolates found so far are sensitive to
spore killing. All seven Spore killer types differ in the percentage of asci that
show killing and in their mutual interactions. Interactions among Spore killer
types showed either mutual resistance or dominant epistasis. Most killer elements
could be assigned to linkage group III but are not tightly linked to the
centromere.
PMID- 11014810
TI - Respiratory chain complex I is essential for sexual development in neurospora and
binding of iron sulfur clusters are required for enzyme assembly.
AB - We have cloned and disrupted in vivo, by repeat-induced point mutations, the
nuclear gene coding for an iron sulfur subunit of complex I from Neurospora
crassa, homologue of the mammalian TYKY protein. Analysis of the obtained mutant
nuo21.3c revealed that complex I fails to assemble. The peripheral arm of the
enzyme is disrupted while its membrane arm accumulates. Furthermore, mutated
21.3c-kD proteins, in which selected cysteine residues were substituted with
alanines or serines, were expressed in mutant nuo21. 3c. The phenotypes of these
strains regarding the formation of complex I are similar to that of the original
mutant, indicating that binding of iron sulfur centers to protein subunits is a
prerequisite for complex I assembly. Homozygous crosses of nuo21.3c strain, and
of other complex I mutants, are unable to complete sexual development. The
crosses are blocked at an early developmental stage, before fusion of the nuclei
of opposite mating types. This phenotype can be rescued only by transformation
with the intact gene. Our results suggest that this might be due to the
compromised capacity of complex I-defective strains in energy production.
PMID- 11014811
TI - Caenorhabditis elegans msh-5 is required for both normal and radiation-induced
meiotic crossing over but not for completion of meiosis.
AB - Crossing over and chiasma formation during Caenorhabditis elegans meiosis require
msh-5, which encodes a conserved germline-specific MutS family member. msh-5
mutant oocytes lack chiasmata between homologous chromosomes, and crossover
frequencies are severely reduced in both oocyte and spermatocyte meiosis.
Artificially induced DNA breaks do not bypass the requirement for msh-5,
suggesting that msh-5 functions after the initiation step of meiotic
recombination. msh-5 mutants are apparently competent to repair breaks induced
during meiosis, but accomplish repair in a way that does not lead to crossovers
between homologs. These results combine with data from budding yeast to establish
a conserved role for Msh5 proteins in promoting the crossover outcome of meiotic
recombination events. Apart from the crossover deficit, progression through
meiotic prophase is largely unperturbed in msh-5 mutants. Homologous chromosomes
are fully aligned at the pachytene stage, and germ cells survive to complete
meiosis and gametogenesis with high efficiency. Our demonstration that
artificially induced breaks generate crossovers and chiasmata using the normal
meiotic recombination machinery suggests (1) that association of breaks with a
preinitiation complex is not a prerequisite for entering the meiotic
recombination pathway and (2) that the decision for a subset of recombination
events to become crossovers is made after the initiation step.
PMID- 11014812
TI - A region of the myosin rod important for interaction with paramyosin in
Caenorhabditis elegans striated muscle.
AB - The precise arrangement of molecules within the thick filament, as well as the
mechanisms by which this arrangement is specified, remains unclear. In this
article, we have exploited a unique genetic interaction between one isoform of
myosin heavy chain (MHC) and paramyosin in Caenorhabditis elegans to probe the
molecular interaction between MHC and paramyosin in vivo. Using chimeric myosin
constructs, we have defined a 322-residue region of the MHC A rod critical for
suppression of the structural and motility defects associated with the unc
15(e73) allele. Chimeric constructs lacking this region of MHC A either fail to
suppress, or act as dominant enhancers of, the e73 phenotype. Although the 322
residue region is required for suppression activity, our data suggest that
sequences along the length of the rod also play a role in the isoform-specific
interaction between MHC A and paramyosin. Our genetic and cell biological
analyses of construct behavior suggest that the 322-residue region of MHC A is
important for thick filament stability. We present a model in which this region
mediates an avid interaction between MHC A and paramyosin in parallel arrangement
in formation of the filament arms.
PMID- 11014813
TI - A screen for new trithorax group genes identified little imaginal discs, the
Drosophila melanogaster homologue of human retinoblastoma binding protein 2.
AB - The proteins encoded by two groups of conserved genes, the Polycomb and trithorax
groups, have been proposed to maintain, at the level of chromatin structure, the
expression pattern of homeotic genes during Drosophila development. To identify
new members of the trithorax group, we screened a collection of deficiencies for
intergenic noncomplementation with a mutation in ash1, a trithorax group gene.
Five of the noncomplementing deletions uncover genes previously classified as
members of the Polycomb group. This evidence suggests that there are actually
three groups of genes that maintain the expression pattern of homeotic genes
during Drosophila development. The products of the third group appear to be
required to maintain chromatin in both transcriptionally inactive and active
states. Six of the noncomplementing deficiencies uncover previously unidentified
trithorax group genes. One of these deficiencies removes 25D2-3 to 26B2-5. Within
this region, there are two, allelic, lethal P-insertion mutations that identify
one of these new trithorax group genes. The gene has been called little imaginal
discs based on the phenotype of mutant larvae. The protein encoded by the little
imaginal discs gene is the Drosophila homologue of human retinoblastoma binding
protein 2.
PMID- 11014814
TI - Isolation and analysis of six timeless alleles that cause short- or long-period
circadian rhythms in Drosophila.
AB - In genetic screens for Drosophila mutations affecting circadian locomotion
rhythms, we have isolated six new alleles of the timeless (tim) gene. Two of
these mutations cause short-period rhythms of 21-22 hr in constant darkness, and
four result in long-period cycles of 26-28 hr. All alleles are semidominant.
Studies of the genetic interactions of some of the tim alleles with period
altering period (per) mutations indicate that these interactions are close to
multiplicative; a given allele changes the period length of the genetic
background by a fixed percentage, rather than by a fixed number of hours. The
tim(L1) allele was studied in molecular detail. The long behavioral period of
tim(L1) is reflected in a lengthened molecular oscillation of per and tim RNA and
protein levels. The lengthened period is partly caused by delayed nuclear
translocation of TIM(L1) protein, shown directly by immunocytochemistry and
indirectly by an analysis of the phase response curve of tim(L1) flies.
PMID- 11014815
TI - Regulation by homeoproteins: a comparison of deformed-responsive elements.
AB - Homeotic genes of Drosophila melanogaster encode transcription factors that
specify segment identity by activating the appropriate set of target genes
required to produce segment-specific characteristics. Advances in understanding
target gene selection have been hampered by the lack of genes known to be
directly regulated by the HOM-C proteins. Here we present evidence that the gene
1.28 is likely to be a direct target of Deformed in the maxillary segment. We
identified a 664-bp Deformed Response Element (1.28 DRE) that directs maxillary
specific expression of a reporter gene in transgenic embryos. The 1.28 DRE
contains in vitro binding sites for Deformed and DEAF-1. The Deformed binding
sites do not have the consensus sequence for cooperative binding with the
cofactor Extradenticle, and we do not detect cooperative binding to these sites,
though we cannot rule out an independent role for Extradenticle. Removing the
four Deformed binding sites renders the 1.28 DRE inactive in vivo, demonstrating
that these sites are necessary for activation of this enhancer element, and
supporting the proposition that 1.28 is activated by Deformed. We show that the
DEAF-1 binding region is not required for enhancer function. Comparisons of the
1.28 DRE with other known Deformed-responsive enhancers indicate that there are
multiple ways to construct Deformed Response Elements.
PMID- 11014816
TI - Quantitative trait loci that control vector competence for dengue-2 virus in the
mosquito Aedes aegypti.
AB - Quantitative trait loci (QTL) affecting the ability of the mosquito Aedes aegypti
to become infected with dengue-2 virus were mapped in an F(1) intercross. Dengue
susceptible A. aegypti aegypti were crossed with dengue refractory A. aegypti
formosus. F(2) offspring were analyzed for midgut infection and escape barriers.
In P(1) and F(1) parents and in 207 F(2) individuals, regions of 14 cDNA loci
were analyzed with single-strand conformation polymorphism analysis to identify
and orient linkage groups with respect to chromosomes I-III. Genotypes were also
scored at 57 RAPD-SSCP loci, 5 (TAG)(n) microsatellite loci, and 6 sequence
tagged RAPD loci. Dengue infection phenotypes were scored in 86 F(2) females. Two
QTL for a midgut infection barrier were detected with standard and composite
interval mapping on chromosomes II and III that accounted for approximately 30%
of the phenotypic variance (sigma(2)(p)) in dengue infection and these accounted
for 44 and 56%, respectively, of the overall genetic variance (sigma(2)(g)). QTL
of minor effect were detected on chromosomes I and III, but these were not
detected with composite interval mapping. Evidence for a QTL for midgut escape
barrier was detected with standard interval mapping but not with composite
interval mapping on chromosome III.
PMID- 11014817
TI - Male-killing Wolbachia in Drosophila: a temperature-sensitive trait with a
threshold bacterial density.
AB - Inherited microorganisms that disturb the reproduction of their host have been
characterized from a number of host taxa. To understand the general principles
underlying the genetic and mechanistic basis of interactions, study of different
agents in model host species is required. To this end, the nature and genetics of
the maternally inherited sex-ratio trait of Drosophila bifasciata were
investigated. Successful curing of affected lines with antibiotics demonstrated
this trait was associated with the presence of a bacterium, and molecular
systematic analysis demonstrated an association between the presence of the trait
and infection with an A group Wolbachia. The penetrance and heritability of the
trait did not vary with maternal age. Exposure to elevated temperatures did
reduce trait penetrance but did not affect heritability. Examination of the
effect of temperature on bacterial density in eggs revealed a decrease in
bacterial density following exposure of the parent to elevated temperature,
consistent with the hypothesis that male killing in D. bifasciata requires a
threshold density of Wolbachia within eggs. The male offspring produced following
exposure to elevated temperatures were infected with Wolbachia on emergence as
adults. Crossing studies demonstrated a weak cytoplasmic incompatibility
phenotype exhibited by Wolbachia in these males. The results are discussed with
respect to the incidence of male killing within the clade Wolbachia, the general
nature of Wolbachia-host interactions, and the prospects for using this
association to investigate the mechanism of male killing.
PMID- 11014818
TI - The Drosophila mus101 gene, which links DNA repair, replication and condensation
of heterochromatin in mitosis, encodes a protein with seven BRCA1 C-terminus
domains.
AB - The mutagen-sensitive-101 (mus101) gene of Drosophila melanogaster was first
identified 25 years ago through mutations conferring larval hypersensitivity to
DNA-damaging agents. Other alleles of mus101 causing different phenotypes were
later isolated: a female sterile allele results in a defect in a tissue-specific
form of DNA synthesis (chorion gene amplification) and lethal alleles cause
mitotic chromosome instability that can be observed genetically and
cytologically. The latter phenotype presents as a striking failure of mitotic
chromosomes of larval neuroblasts to undergo condensation of pericentric
heterochromatic regions, as we show for a newly described mutant carrying lethal
allele mus101(lcd). To gain further insight into the function of the Mus101
protein we have molecularly cloned the gene using a positional cloning strategy.
We report here that mus101 encodes a member of the BRCT (BRCA1 C terminus) domain
superfamily of proteins implicated in DNA repair and cell cycle checkpoint
control. Mus101, which contains seven BRCT domains distributed throughout its
length, is most similar to human TopBP1, a protein identified through its in
vitro association with DNA topoisomerase IIbeta. Mus101 also shares sequence
similarity with the fission yeast Rad4/Cut5 protein required for repair,
replication, and checkpoint control, suggesting that the two proteins may be
functional homologs.
PMID- 11014819
TI - Semaphorin-1a acts in concert with the cell adhesion molecules fasciclin II and
connectin to regulate axon fasciculation in Drosophila.
AB - Semaphorins comprise a large family of phylogenetically conserved secreted and
transmembrane glycoproteins, many of which have been implicated in repulsive axon
guidance events. The transmembrane semaphorin Sema-1a in Drosophila is expressed
on motor axons and is required for the generation of neuromuscular connectivity.
Sema-1a can function as an axonal repellent and mediates motor axon
defasciculation. Here, by manipulating the levels of Sema-1a and the cell
adhesion molecules fasciclin II (Fas II) and connectin (Conn) on motor axons, we
provide further evidence that Sema-1a mediates axonal defasciculation events by
acting as an axonally localized repellent and that correct motor axon guidance
results from a balance between attractive and repulsive guidance cues expressed
on motor neurons.
PMID- 11014820
TI - Identification of genomic regions that interact with a viable allele of the
Drosophila protein tyrosine phosphatase corkscrew.
AB - Signaling by receptor tyrosine kinases (RTKs) is critical for a multitude of
developmental decisions and processes. Among the molecules known to transduce the
RTK-generated signal is the nonreceptor protein tyrosine phosphatase Corkscrew
(Csw). Previously, Csw has been demonstrated to function throughout the
Drosophila life cycle and, among the RTKs tested, Csw is essential in the Torso,
Sevenless, EGF, and Breathless/FGF RTK pathways. While the biochemical function
of Csw remains to be unambiguously elucidated, current evidence suggests that Csw
plays more than one role during transduction of the RTK signal and, further, the
molecular mechanism of Csw function differs depending upon the RTK in question.
The isolation and characterization of a new, spontaneously arising, viable allele
of csw, csw(lf), has allowed us to undertake a genetic approach to identify loci
required for Csw function. The rough eye and wing vein gap phenotypes exhibited
by adult flies homo- or hemizygous for csw(lf) has provided a sensitized
background from which we have screened a collection of second and third
chromosome deficiencies to identify 33 intervals that enhance and 21 intervals
that suppress these phenotypes. We have identified intervals encoding known
positive mediators of RTK signaling, e.g., drk, dos, Egfr, E(Egfr)B56, pnt, Ras1,
rolled/MAPK, sina, spen, Src64B, Star, Su(Raf)3C, and vein, as well as known
negative mediators of RTK signaling, e.g., aos, ed, net, Src42A, sty, and su(ve).
Of particular interest are the 5 lethal enhancing intervals and 14 suppressing
intervals for which no candidate genes have been identified.
PMID- 11014821
TI - The LAMMER protein kinase encoded by the Doa locus of Drosophila is required in
both somatic and germline cells and is expressed as both nuclear and cytoplasmic
isoforms throughout development.
AB - Activity of the Darkener of apricot (Doa) locus of Drosophila melanogaster is
required for development of the embryonic nervous system, segmentation,
photoreceptor maintenance, normal transcription, and sexual differentiation. The
gene encodes a protein kinase, with homologues throughout eukaryotes known as the
LAMMER kinases. We show here that DOA is expressed as at least two different
protein isoforms of 105 and 55 kD throughout development, which are primarily
localized to the cytoplasm and nucleus, respectively. Doa transcripts and protein
are expressed in all cell types both during embryogenesis and in imaginal discs.
Although it was recently shown that DOA kinase is essential for normal sexual
differentiation, levels of both kinase isoforms are equal between the sexes
during early pupal development. The presence of the kinase on the cell membrane
and in the nuclei of polytene salivary gland cells, as well as exclusion from the
nuclei of specific cells, may be indicative of regulated kinase localization.
Mosaic analysis in both the soma and germline demonstrates that Doa function is
essential for cell viability. Finally, in contrast to results reported in other
systems and despite some phenotypic similarities, genetic data demonstrate that
the LAMMER kinases do not participate in the ras-MAP kinase signal transduction
pathway.
PMID- 11014822
TI - Identification of autosomal regions involved in Drosophila Raf function.
AB - Raf is an essential downstream effector of activated p21(Ras) (Ras) in
transducing proliferation or differentiation signals. Following binding to Ras,
Raf is translocated to the plasma membrane, where it is activated by a yet
unidentified "Raf activator." In an attempt to identify the Raf activator or
additional molecules involved in the Raf signaling pathway, we conducted a
genetic screen to identify genomic regions that are required for the biological
function of Drosophila Raf (Draf). We tested a collection of chromosomal
deficiencies representing approximately 70% of the autosomal euchromatic genomic
regions for their abilities to enhance the lethality associated with a
hypomorphic viable allele of Draf, Draf(Su2). Of the 148 autosomal deficiencies
tested, 23 behaved as dominant enhancers of Draf(Su2), causing lethality in
Draf(Su2) hemizygous males. Four of these deficiencies identified genes known to
be involved in the Drosophila Ras/Raf (Ras1/Draf) pathway: Ras1, rolled (rl,
encoding a MAPK), 14-3-3epsilon, and bowel (bowl). Two additional deficiencies
removed the Drosophila Tec and Src homologs, Tec29A and Src64B. We demonstrate
that Src64B interacts genetically with Draf and that an activated form of Src64B,
when overexpressed in early embryos, causes ectopic expression of the Torso (Tor)
receptor tyrosine kinase-target gene tailless. In addition, we show that a
mutation in Tec29A partially suppresses a gain-of-function mutation in tor. These
results suggest that Tec29A and Src64B are involved in Tor signaling, raising the
possibility that they function to activate Draf. Finally, we discovered a genetic
interaction between Draf(Su2) and Df(3L)vin5 that revealed a novel role of Draf
in limb development. We find that loss of Draf activity causes limb defects,
including pattern duplications, consistent with a role for Draf in regulation of
engrailed (en) expression in imaginal discs.
PMID- 11014823
TI - Nonrandom segregation of the mouse univalent X chromosome: evidence of spindle
mediated meiotic drive.
AB - A fundamental principle of Mendelian inheritance is random segregation of alleles
to progeny; however, examples of distorted transmission either of specific
alleles or of whole chromosomes have been described in a variety of species. In
humans and mice, a distortion in chromosome transmission is often associated with
a chromosome abnormality. One such example is the fertile XO female mouse. A
transmission distortion effect that results in an excess of XX over XO daughters
among the progeny of XO females has been recognized for nearly four decades.
Utilizing contemporary methodology that combines immunofluorescence, FISH, and
three-dimensional confocal microscopy, we have readdressed the meiotic
segregation behavior of the single X chromosome in oocytes from XO females
produced on two different inbred backgrounds. Our studies demonstrate that
segregation of the univalent X chromosome at the first meiotic division is
nonrandom, with preferential retention of the X chromosome in the oocyte in
approximately 60% of cells. We propose that this deviation from Mendelian
expectations is facilitated by a spindle-mediated mechanism. This mechanism,
which appears to be a general feature of the female meiotic process, has
implications for the frequency of nondisjunction in our species.
PMID- 11014824
TI - Evolution of odorant receptors expressed in mammalian testes.
AB - About 10% of mammalian odorant receptors are transcribed in testes, and odorant
receptor proteins have been detected on mature spermatozoa. Testis-expressed
odorant receptors (TORs) are hypothesized to play roles in sperm chemotaxis, but
they might also be ordinary nasal odorant receptors (NORs) that are expressed
gratuitously in testes. Under the sperm-chemotaxis hypothesis, TORs should be
subject to intense sexual selection and therefore should show higher rates of
amino acid substitution than NORs, but under the gratuitous-expression
hypothesis, TORs are misidentified NORs and therefore should evolve like other
NORs. To test these predictions, we estimated synonymous and nonsynonymous
divergences of orthologous NOR and TOR coding sequences from rat and mouse.
Contrary to both hypotheses, TORs are on average more highly conserved than NORs,
especially in certain domains of the OR protein. This pattern suggests that some
TORs might perform internal nonolfactory functions in testes; for example, they
might participate in the regulation of sperm development. However, the pattern is
also consistent with a modified gratuitous-expression model in which NORs with
specialized ligand specificities are both more highly conserved than typical NORs
and more likely to be expressed in testes.
PMID- 11014825
TI - Archaic lineages in the history of modern humans.
AB - An important question in the ongoing debate on the origin of Homo sapiens is
whether modern human populations issued from a single lineage or whether several,
independently evolving lineages contributed to their genetic makeup. We analyzed
haplotypes composed of 35 polymorphisms from a segment of the dystrophin gene. We
find that the bulk of a worldwide sample of 868 chromosomes represents haplotypes
shared by different continental groups. The remaining chromosomes carry
haplotypes specific for the continents or for local populations. The haplotypes
specific for non-Africans can be derived from the most frequent ones through
simple recombination or a mutation. In contrast, chromosomes specific for sub
Saharan Africans represent a distinct group, as shown by principal component
analysis, maximum likelihood tree, structural comparison, and summary statistics.
We propose that African chromosomes descend from at least two lineages that have
been evolving separately for a period of time. One of them underwent range
expansion colonizing different continents, including Africa, where it mixed with
another, local lineage represented today by a large fraction of African-specific
haplotypes. Genetic admixture involving archaic lineages appears therefore to
have occurred within Africa rather than outside this continent, explaining
greater diversity of sub-Saharan populations observed in a variety of genetic
systems.
PMID- 11014827
TI - Gene flow in a facultative apomictic poacea, the savanna grass Hyparrhenia
diplandra.
AB - The genetics of the poacea Hyparrhenia diplandra was studied in four natural
populations from an ecological station in West Africa, where it makes up 80% of
grasses from wet savanna and constitutes a dense continuum of randomly
distributed individuals. DNA content and cytogenetical observations suggest it is
an allotetraploid. Using two highly variable microsatellites (heterozygosity H =
0.615-0.616), we show that this species is an apomict with rare sexual
reproduction events that account for approximately 0.5% of seeds pollinated in
the wild. Hexaploid individuals were also produced, corroborating the observation
of aberrant genotypes in the wild. The spatial extent of asexual clones in the
field was low in comparison with the predominance of apomixis, thus indicating a
low dispersal of seeds from their parent. Heterozygosity and departure from Hardy
Weinberg predictions were similar in the four populations, revealing a high
apparent selfing rate s = 0.599 among sexually produced seeds. This is an
overestimate since we could not distinguish true selfing from reciprocal
outcrosses between neighboring individuals from the same apomictic clone. Gene
flow by pollen could be substantial, possibly explaining the absence of isolation
by distance in the studied area.
PMID- 11014826
TI - Mechanisms involved in targeted gene replacement in mammalian cells.
AB - The "ends-out" or omega (Omega)-form gene replacement vector is used routinely to
perform targeted genome modification in a variety of species and has the
potential to be an effective vehicle for gene therapy. However, in mammalian
cells, the frequency of this reaction is low and the mechanism unknown.
Understanding molecular features associated with gene replacement is important
and may lead to an increase in the efficiency of the process. In this study, we
investigated gene replacement in mammalian cells using a powerful assay system
that permits efficient recovery of the product(s) of individual recombination
events at the haploid, chromosomal mu-delta locus in a murine hybridoma cell
line. The results showed that (i) heteroduplex DNA (hDNA) is formed during
mammalian gene replacement; (ii) mismatches in hDNA are usually efficiently
repaired before DNA replication and cell division; (iii) the gene replacement
reaction occurs with fidelity; (iv) the presence of multiple markers in one
homologous flanking arm in the replacement vector did not affect the efficiency
of gene replacement; and (v) in comparison to a genomic fragment bearing
contiguous homology to the chromosomal target, gene targeting was only slightly
inhibited by internal heterology (pSV2neo sequences) in the replacement vector.
PMID- 11014828
TI - Comparative fluorescence in situ hybridization mapping of a 431-kb Arabidopsis
thaliana bacterial artificial chromosome contig reveals the role of chromosomal
duplications in the expansion of the Brassica rapa genome.
AB - Comparative genome studies are important contributors to our understanding of
genome evolution. Most comparative genome studies in plants have been based on
genetic mapping of homologous DNA loci in different genomes. Large-scale
comparative physical mapping has been hindered by the lack of efficient and
affordable techniques. We report here the adaptation of fluorescence in situ
hybridization (FISH) techniques for comparative physical mapping between
Arabidopsis thaliana and Brassica rapa. A set of six bacterial artificial
chromosomes (BACs) representing a 431-kb contiguous region of chromosome 2 of A.
thaliana was mapped on both chromosomes and DNA fibers of B. rapa. This DNA
fragment has a single location in the A. thaliana genome, but hybridized to four
to six B. rapa chromosomes, indicating multiple duplications in the B. rapa
genome. The sizes of the fiber-FISH signals from the same BACs were not longer in
B. rapa than those in A. thaliana, suggesting that this genomic region is
duplicated but not expanded in the B. rapa genome. The comparative fiber-FISH
mapping results support that chromosomal duplications, rather than regional
expansion due to accumulation of repetitive sequences in the intergenic regions,
played the major role in the evolution of the B. rapa genome.
PMID- 11014829
TI - Hierarchical patterns of transgene expression indicate involvement of
developmental mechanisms in the regulation of the maize P1-rr promoter.
AB - The maize P1-rr gene encodes a Myb-homologous transcription factor that regulates
the synthesis of red flavonoid pigments. Maize plants transformed with segments
of the P1-rr promoter driving a GUS reporter gene exhibit significant variation
in transgene expression, both between independent transformation events and among
sibling plants derived from a single event. Interestingly, variability in spatial
expression is not random; rather, transgene activity occurs predominantly in five
patterns that fit a hierarchy: expression is most common in kernel pericarp, with
sequential addition of expression in cob glumes, husk, silk, and tassel. The
hierarchical expression pattern of P-rr::GUS transgenes suggests a possible model
for developmental regulation of the P1-rr gene. Our results demonstrate that
variability in transgene expression, a common occurrence in transgenic plant
studies, can be informative if adequately analyzed to uncover underlying patterns
of gene expression.
PMID- 11014830
TI - Computational and experimental characterization of physically clustered simple
sequence repeats in plants.
AB - The type and frequency of simple sequence repeats (SSRs) in plant genomes was
investigated using the expanding quantity of DNA sequence data deposited in
public databases. In Arabidopsis, 306 genomic DNA sequences longer than 10 kb and
36,199 EST sequences were searched for all possible mono- to pentanucleotide
repeats. The average frequency of SSRs was one every 6.04 kb in genomic DNA,
decreasing to one every 14 kb in ESTs. SSR frequency and type differed between
coding, intronic, and intergenic DNA. Similar frequencies were found in other
plant species. On the basis of these findings, an approach is proposed and
demonstrated for the targeted isolation of single or multiple, physically
clustered SSRs linked to any gene that has been mapped using low-copy DNA-based
markers. The approach involves sample sequencing a small number of subclones of
selected randomly sheared large insert DNA clones (e.g., BACs). It is shown to be
both feasible and practicable, given the probability of fortuitously sequencing
through an SSR. The approach is demonstrated in barley where sample sequencing 34
subclones of a single BAC selected by hybridization to the Big1 gene revealed
three SSRs. These allowed Big1 to be located at the top of barley linkage group
6HS.
PMID- 11014831
TI - On the differences between maximum likelihood and regression interval mapping in
the analysis of quantitative trait loci.
AB - The differences between maximum-likelihood (ML) and regression (REG) interval
mapping in the analysis of quantitative trait loci (QTL) are investigated
analytically and numerically by simulation. The analytical investigation is based
on the comparison of the solution sets of the ML and REG methods in the
estimation of QTL parameters. Their differences are found to relate to the
similarity between the conditional posterior and conditional probabilities of QTL
genotypes and depend on several factors, such as the proportion of variance
explained by QTL, relative QTL position in an interval, interval size, difference
between the sizes of QTL, epistasis, and linkage between QTL. The differences in
mean squared error (MSE) of the estimates, likelihood-ratio test (LRT) statistics
in testing parameters, and power of QTL detection between the two methods become
larger as (1) the proportion of variance explained by QTL becomes higher, (2) the
QTL locations are positioned toward the middle of intervals, (3) the QTL are
located in wider marker intervals, (4) epistasis between QTL is stronger, (5) the
difference between QTL effects becomes larger, and (6) the positions of QTL get
closer in QTL mapping. The REG method is biased in the estimation of the
proportion of variance explained by QTL, and it may have a serious problem in
detecting closely linked QTL when compared to the ML method. In general, the
differences between the two methods may be minor, but can be significant when QTL
interact or are closely linked. The ML method tends to be more powerful and to
give estimates with smaller MSEs and larger LRT statistics. This implies that ML
interval mapping can be more accurate, precise, and powerful than REG interval
mapping. The REG method is faster in computation, especially when the number of
QTL considered in the model is large. Recognizing the factors affecting the
differences between REG and ML interval mapping can help an efficient strategy,
using both methods in QTL mapping to be outlined.
PMID- 11014833
TI - Consequences of recombination on traditional phylogenetic analysis.
AB - We investigate the shape of a phylogenetic tree reconstructed from sequences
evolving under the coalescent with recombination. The motivation is that
evolutionary inferences are often made from phylogenetic trees reconstructed from
population data even though recombination may well occur (mtDNA or viral
sequences) or does occur (nuclear sequences). We investigate the size and
direction of biases when a single tree is reconstructed ignoring recombination.
Standard software (PHYLIP) was used to construct the best phylogenetic tree from
sequences simulated under the coalescent with recombination. With recombination
present, the length of terminal branches and the total branch length are larger,
and the time to the most recent common ancestor smaller, than for a tree
reconstructed from sequences evolving with no recombination. The effects are
pronounced even for small levels of recombination that may not be immediately
detectable in a data set. The phylogenies when recombination is present
superficially resemble phylogenies for sequences from an exponentially growing
population. However, exponential growth has a different effect on statistics such
as Tajima's D. Furthermore, ignoring recombination leads to a large
overestimation of the substitution rate heterogeneity and the loss of the
molecular clock. These results are discussed in relation to viral and mtDNA data
sets.
PMID- 11014832
TI - The implications of intergenic polymorphism for major histocompatibility complex
evolution.
AB - A systematic survey of six intergenic regions flanking the human HLA-B locus in
eight haplotypes reveals the regions to be up to 20 times more polymorphic than
the reported average degree of human neutral polymorphism. Furthermore, the
extent of polymorphism is directly related to the proximity to the HLA-B locus.
Apparently linkage to HLA-B locus alleles, which are under balancing selection,
maintains the neutral polymorphism of adjacent regions. For these linked
polymorphisms to persist, recombination in the 200-kb interval from HLA-B to TNF
must occur at a low frequency. The high degree of polymorphism found distal to
HLA-B suggests that recombination is uncommon on both sides of the HLA-B locus.
The least-squares estimate is 0.15% per megabase with an estimated range from
0.02 to 0.54%. These findings place strong restrictions on possible
recombinational mechanisms for the generation of diversity at the HLA-B.
PMID- 11014834
TI - The evolution of haploid, diploid and polymorphic haploid-diploid life cycles:
the role of meiotic mutation.
AB - Here I present a simple population genetic model to investigate the evolution of
polymorphic haploid-diploid life cycles. The key feature of the model is the
assumption of mutation occurring during meiosis. I show that, in addition to
regions favoring haploid or diploid life cycles, there are substantial regions of
the parameter space under which polymorphic haploid-diploid life cycles are
expected to evolve.
PMID- 11014835
TI - Multitrait least squares for quantitative trait loci detection.
AB - A multiple-trait QTL mapping method using least squares is described. It is
presented as an extension of a single-trait method for use with three-generation,
outbred pedigrees. The multiple-trait framework allows formal testing of whether
the same QTL affects more than one trait (i.e., a pleiotropic QTL) or whether
more than one linked QTL are segregating. Several approaches to the testing
procedure are presented and their suitability discussed. The performance of the
method is investigated by simulation. As previously found, multitrait analyses
increase the power to detect a pleiotropic QTL and the precision of its location
estimate. With enough information, discrimination between alternative genetic
models is possible.
PMID- 11014836
TI - Statistical models for estimating the genetic basis of repeated measures and
other function-valued traits.
AB - The genetic analysis of characters that are best considered as functions of some
independent and continuous variable, such as age, can be a complicated matter,
and a simple and efficient procedure is desirable. Three methods are common in
the literature: random regression, orthogonal polynomial approximation, and
character process models. The goals of this article are (i) to clarify the
relationships between these methods; (ii) to develop a general extension of the
character process model that relaxes correlation stationarity, its most stringent
assumption; and (iii) to compare and contrast the techniques and evaluate their
performance across a range of actual and simulated data. We find that the
character process model, as described in 1999 by Pletcher and Geyer, is the most
successful method of analysis for the range of data examined in this study. It
provides a reasonable description of a wide range of different covariance
structures, and it results in the best models for actual data. Our analysis
suggests genetic variance for Drosophila mortality declines with age, while
genetic variance is constant at all ages for reproductive output. For growth in
beef cattle, however, genetic variance increases linearly from birth, and genetic
correlations are high across all observed ages.
PMID- 11014837
TI - Simple and rapid method for the detection of early signs of toxicity in Daphnia
magna straus.
PMID- 11014838
TI - Endocrine disruption by hexachlorobenzene in Crucian carp (Carassius auratus
gibelio).
PMID- 11014841
TI - Lead concentrations in Eucalyptus sp. in a small coastal town.
PMID- 11014839
TI - Toxicity response of Emerita analoga (Stimpson, 1857) collected from beaches of
South Central Chile.
PMID- 11014842
TI - Metals in water in the Central Kalimantan, Indonesia.
PMID- 11014843
TI - Migration of lead and cadmium from ceramic materials used in food preparation.
PMID- 11014840
TI - Mercury bioaccumulation induces oxidative stress and toxicity to submerged
macrophyte Potamogeton crispus L.
PMID- 11014844
TI - Metals and selenium in Sand Martin's plumage.
PMID- 11014846
TI - Bioconcentration of endosulfan and monocrotophos by Labeo rohita and Channa
punctata.
PMID- 11014847
TI - Toxicity and bioconcentration of chlorpyrifos in aquatic organisms: Artemia
parthenogenetica(Crustacea), Gambusia affinis, and Aphanius iberus (Pisces).
PMID- 11014845
TI - Determination of the bioconcentration of phosphamidon and profenofos in zebrafish
(Brachydanio rerio).
PMID- 11014848
TI - Measurement of benzo(a)pyrene in sea water and in mussels in the Seto Inland Sea,
Japan.
PMID- 11014853
TI - Comparison of different treatments for alachlor removal from water.
PMID- 11014852
TI - Identification of hydrocarbons and oxygen compounds in sediments from Niigata,
Japan.
PMID- 11014849
TI - Cadmium uptake by Corbicula fluminea and Dreissena polymorpha: effects of pH and
temperature.
PMID- 11014850
TI - Time-related increase of hydrocarbons in barnacles in the north-western waters of
the Arabian gulf.
PMID- 11014854
TI - Management of fly ash landfills with Cassia surattensis Burm: a case study.
PMID- 11014856
TI - Fluctuations and fractal noise in biological membranes.
AB - Our understanding of cell structure and function derives from applications of a
variety of physical and life science disciplines, methods and models to an
important physiological process, namely, the exchange and transport of ions and
molecules across biological membranes. We know that ion transport through
membranes arises from a diversity of interrelated and interactive physical and
chemical phenomena over a wide range of spatial and temporal scales. Among these
phenomena common to all cellular structure and function include metabolism,
kinetics of molecules, chemically mediated alteration of cell membrane electrical
potential, membrane ion conductance, electrical signal propagation, and
modulation by chemo- and mechanoreceptive mechanisms. This review focuses on the
unique information contained in fluctuations in electrical properties associated
with cell membrane ion transport.
PMID- 11014855
TI - Fluoride removal from water by Hydrilla verticillata (l.f.) royle and its toxic
effects.
PMID- 11014851
TI - Surveys of volatile organic compounds in soil and groundwater at industrial sites
in Taiwan.
PMID- 11014857
TI - Reactivity of cysteines in the transmembrane region of the Na, K-ATPase alpha
subunit probed with Hg(2+).
AB - To gain insight into the structure and conformational coupling in the Na,K
ATPase, this study characterized the reaction of the alpha1 subunit transmembrane
cysteines with a small probe. Intact HeLa cells expressing heterologous Na,K
ATPase were treated with (microm) HgCl(2) after placing the enzyme predominantly
in either of two conformations, phosphorylated E2P.Na/E2P or dephosphorylated
ATP.E1. K/ATP.E1. Under both conditions the treatment led to enzyme inactivation
following a double exponential kinetic as determined by ouabain-sensitive K(+)
uptake measurements. However, the rate constant of the slow reacting component
was ten times larger when the protein was probed in a medium that would favor
enzyme phosphorylation. Enzymes carrying mutations of cysteines located in the
alpha1 subunit transmembrane region were used to identify the reacting-SH groups.
Replacement Cys104Ser reduced enzyme inactivation by removing the slow reacting
component under both treatment conditions. Replacement of Cys964 reduced the
inactivation rate constant of the fast reacting component (79%) and removed the
slow reacting component when the dephosphorylated enzyme was treated with Hg(2+).
Moreover, Cys964Ser substituted enzyme was insensitive to Hg(2+) when treated
under phosphorylation conditions. These results indicate that Cys964 is involved
in the fast inactivation by Hg(2+). Although the double mutant Cys964, 104Ser was
still partially inactivated by treatment under nonphosphorylating conditions, an
enzyme devoid of transmembrane cysteines was insensitive to Hg(2+) under all
treatment conditions. Thus, this enzyme provides a background where accessibility
of engineered transmembrane cysteines can be tested.
PMID- 11014861
TI - Mechanism of shrinkage activation of nonselective cation channels in M-1 mouse
cortical collecting duct cells.
AB - It has previously been shown that osmotic cell shrinkage activates a nonselective
cation (NSC) channel in M-1 mouse cortical collecting duct cells [54] and in a
variety of other cell types [20]. In the present study we further characterized
the shrinkage-activated NSC channel in M-1 cells and its mechanism of activation
using whole-cell current recordings. Osmotic cell shrinkage induced by addition
of 100 mm sucrose to the bath solution caused a 20-fold increase in whole-cell
inward currents from -10.8 +/- 1.5 pA to -211 +/- 10.2 pA (n = 103). A similar
response was observed when cell shrinkage was elicited using a hypo-osmotic
pipette solution. This indicates that cell shrinkage and not extracellular
osmolarity per se is the signal for current activation. Cation substitution
experiments revealed that the activated channels discriminate poorly between
monovalent cations with a selectivity sequence NH(4) (1.2) > or = Na(+) (1)
approximately K(+) (0.9) approximately Li(+) (0.9). In contrast there was no
measurable permeability for Ca(2+) or Ba(2+) and the cation-to-anion permeability
ratio was about 14. The DPC-derivatives flufenamic acid, 4-methyl-DPC and DCDPC
were the most effective blockers followed by LOE 908, while amiloride and
bumetanide were ineffective. The putative channel activator maitotoxin had no
effect. Current activation was dependent upon the presence of intracellular ATP
and Mg(2+) and was inhibited by staurosporine (1 microm) and calphostin C (1
microm). Moreover, cytochalasin D (10 microm) and taxol (2 microm) reduced the
current response to cell shrinkage. These findings suggest that the activation
mechanism of the shrinkage-activated NSC channel involves protein kinase mediated
phosphorylation steps and cytoskeletal elements.
PMID- 11014863
TI - The SU glycoprotein 120 from HIV-1 penetrates into lipid monolayers mimicking
plasma membranes.
AB - Increasing evidence suggests that the HIV envelope binds through its surface (SU)
gp120 not only to receptors and coreceptors, but also to other components of the
cellular membrane where the glycolipids appear to be good candidates. To assess
the ability of HIV-1 SU gp120 to penetrate into phospholipid membranes, we
carried out a study of the interactions between a recombinant SU gp120 from HIV
1/HXB2 and artificial lipid monolayers mimicking the composition of the outer
leaflet of the lymphocytes and which were spread at the air-water interface. We
show that the protein, in its aggregated form, has amphipathic properties and
that the insertion of this amphipathic species into lipids is favored by the
presence of sphingomyelin. Furthermore, cholesterol enhances the penetration into
mixed phosphatidylcholine-sphingomyelin monolayers. Coexistence of different
physical states of the lipids and thus of domains appears to play a major role
for protein penetration independently of the presence of receptors and
coreceptors.
PMID- 11014858
TI - Vacuolar chloride transport in Mesembryanthemum crystallinum L. measured using
the fluorescent dye lucigenin.
AB - To study vacuolar chloride (Cl(-)) transport in the halophilic plant
Mesembryanthemum crystallinum L., Cl(-) uptake into isolated tonoplast vesicles
was measured using the Cl(-)-sensitive fluorescent dye lucigenin (N,N'-dimethyl
9,9'-bisacridinium dinitrate). Lucigenin was used at excitation and emission
wavelengths of 433 nm and 506 nm, respectively, and showed a high sensitivity
towards Cl(-), with a Stern-Volmer constant of 173 m(-1) in standard assay
buffer. While lucigenin fluorescence was strongly quenched by all halides, it was
only weakly quenched, if at all, by other anions. However, the fluorescence
intensity and Cl(-)-sensitivity of lucigenin was shown to be strongly affected by
alkaline pH and was dependent on the conjugate base used as the buffering ion.
Chloride transport into tonoplast vesicles of M. crystallinum loaded with 10 mm
lucigenin showed saturation-type kinetics with an apparent K(m) of 17.2 mm and a
V(max) of 4.8 mm min(-1). Vacuolar Cl(-) transport was not affected by sulfate,
malate, or nitrate. In the presence of 250 microm p-chloromercuribenzene
sulfonate, a known anion-transport inhibitor, vacuolar Cl(-) transport was
actually significantly increased by 24%. To determine absolute fluxes of Cl(-)
using this method, the average surface to volume ratio of the tonoplast vesicles
was measured by electron microscopy to be 1.13 x 10(7) m(-1). After correcting
for a 4.4-fold lower apparent Stern-Volmer constant for intravesicular lucigenin,
a maximum rate of Cl(-) transport of 31 nmol m(-2) sec(-1) was calculated, in
good agreement with values obtained for the plant vacuolar membrane using other
techniques.
PMID- 11014859
TI - CFTR regulation of intracellular calcium in normal and cystic fibrosis human
airway epithelia.
AB - In cystic fibrosis airway epithelia, mutation of the CFTR protein causes a
reduced response of Cl(-) secretion to secretagogues acting via cAMP. Using a
Ca(2+) imaging system, the hypothesis that CFTR activation may permit ATP release
and regulate [Ca(2+)](i) via a receptor-mediated mechanism, is tested in this
study. Application of external nucleotides produced a significant increase in
[Ca(2+)](i) in normal (16HBE14o(-) cell line and primary lung culture) and in
cystic fibrosis (CFTE29o(-) cell line) human airway epithelia. The potency order
of nucleotides on [Ca(2+)](i) variation was UTP >> ATP > UDP > ADP > AMP >
adenosine in both cell types. The nucleotide [Ca(2+)](i) response could be
mimicked by activation of CFTR with forskolin (20 microm) in a temperature
dependent manner. In 16HBE14o(-) cells, the forskolin-induced [Ca(2+)](i)
response increased with increasing temperature. In CFTE29o(-) cells, forskolin
had no effect on [Ca(2+)](i) at body temperature-forskolin-induced [Ca(2+)](i)
response in CF cells could only be observed at low experimental temperature (14
degrees C) or when cells were cultured at 26 degrees C instead of 37 degrees C.
Pretreatment with CFTR channel blockers glibenclamide (100 microm) and DPC (100
microm), with hexokinase (0.5 U/mg), and with the purinoceptor antagonist suramin
(100 microm), inhibited the forskolin [Ca(2+)](i) response. Together, these
results demonstrate that once activated, CFTR regulates [Ca(2+)](i) by mediating
nucleotide release and activating cell surface purinoceptors in normal and CF
human airway epithelia.
PMID- 11014862
TI - Inositol 1,4,5-trisphosphate but not ryanodine-receptor agonists induces calcium
release from rat liver Golgi apparatus membrane vesicles.
AB - We investigated the direct effect of inositol 1,4,5-trisphosphate (IP(3)) and
ryanodine receptor agonists on Ca(2+) release from vesicles of a rat liver Golgi
apparatus (GA) enriched fraction, which were actively loaded with (45)Ca(2+).
Results in GA were compared with those obtained in a rat liver endoplasmic
reticulum (ER) enriched fraction. The addition of IP(3) at concentrations ranging
from 100 nm to 100 microm, in the presence of thapsigargin, a specific inhibitor
of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases, promoted a rapid decrease
in the Ca(2+) content of GA vesicles. The amount of Ca(2+) released from the
vesicles was a function of IP(3) concentration, reaching about 60% in both GA and
ER fractions at 100 microm IP(3). Calcium release was inhibited by heparin, an
antagonist of IP(3) receptors. Calcium exhibited a bell-shaped effect on IP(3)
dependent Ca(2+) released from GA vesicles: it activated Ca(2+) release at
concentrations up to 1 microm, and inhibited it at higher concentrations. In
contrast to that found in the endoplasmic reticulum fraction, none of the
ryanodine receptor agonists tested (cyclic ADP-ribose, caffeine and ryanodine)
significantly induced Ca(2+) release from GA fraction vesicles in the presence of
thapsigargin. Our results indicate the presence of an IP(3)-sensitive Ca(2+)
release mechanism in the Golgi apparatus membrane analogous to that of the ER.
However, a Ca(2+) release mechanism sensitive to ryanodine receptor agonists like
that of ER is not evident in the GA membrane.
PMID- 11014860
TI - Cl(-) channels in basolateral TAL membranes XV. Molecular heterogeneity between
cortical and medullary channels.
AB - We have isolated two new and highly homologous cDNAs, mmClC-Ka from mouse outer
medulla and mcClC-Ka from mouse cortex. In both cases, mRNA was obtained from the
indicated region and subjected to RT-PCR using primers from the nucleotide
sequence of rbClC-Ka, which encodes basolateral Cl(-) channels (termed rbClC-Ka)
in rabbit MTAL. The predicted protein products of mmClC-Ka and mcClC-Ka, mmClC-Ka
and mcClC-Ka, respectively, were 85% homologous and had predicted molecular
weights of 75 kDa. The predicted protein sequences for mmClC-Ka and rbClC-Ka had
three cytosolic sites-threonine 185, threonine 187 and serine 270-which were
absent in mcClC-Ka. These three moieties represent potential sites for
phosphorylation of mmClC-Ka and rbClC-Ka, but not of mcClC-Ka, and may account
for the failure of (ATP + PKA) to increase the open time probability P(o) in
basolateral CTAL Cl(-) channels. We prepared antisense oligonucleotides specific
for nonhomologous regions of these two cDNAs, mmAntisense for mmClC-Ka and
mcAntisense for mcClC-Ka. Using anti-rbClC-Ka, a polyclonal antibody to rbClC-Ka,
we found that, when transfected into cultured mouse MTAL and CTAL cells,
mmAntisense suppressed the appearance of the 75 kDa band by 50% in vesicles from
MTAL but not CTAL cells, while transfection of MTAL and CTAL cells with
mcAntisense suppressed appearance of the 75 kDa band in vesicles from CTAL but
not MTAL cells. mmAntisense transfection also prolonged the half-time (T(1/2),
sec) for (36)Cl(-) efflux in cultured MTAL cells from 82.4 +/- 6.8 sec (sem) to
187.8 +/- 9.5 sec (n = 5; P = 0.0001) while mcAntisense transfection had no such
effect. Conversely, in cultured CTAL cells, mcAntisense transfection prolonged
the T(1/2) for (36)Cl(-) efflux from 80.9 +/- 6.3 sec to 191.8 +/- 6.5 sec (n =
5; P = 0.00005), while mmAntisense had no such effect. We conclude that mmClC-Ka
and mcClC-Ka may encode the basolateral Cl(-) channels mediating net Cl(-)
absorption in mouse MTAL and CTAL, respectively.
PMID- 11014864
TI - Properties of hexadecaprenyl monophosphate/dioleoylphosphatidylcholine vesicular
lipid bilayers.
AB - In our study we investigated hemispherical phospholipid bilayer membranes and
phospholipid vesicles made from hexadecaprenyl monophosphate (C(80)-P),
dioleoylphosphatidylocholine (DOPC) and their mixtures by voltammetric and
transmission electron microscopy (TEM) techniques. The current-voltage
characteristics, the membrane conductance-temperature relationships and the
membrane breakdown voltage have been measured for different mixtures of C(80)
P/DOPC. The membrane hydrophobic thickness and the activation energy of ion
migration across the membrane have been determined. Hexadecaprenyl monophosphate
decreased in comparison with DOPC bilayers, the membrane conductance, increased
the activation energy and the membrane breakdown voltage for the various value of
C(80)-P/DOPC mole ratio, respectively. The TEM micrographs of C(80)-P, DOPC and
C(80)-P/DOPC lipid vesicles showed several characteristic structures, which have
been described. The data indicate that hexadecaprenyl monophosphate modulates the
surface curvature of the membranes by the formation of aggregates in liquid
crystalline phospholipid membranes. We suggest that the dynamics and conformation
of hexadecaprenyl monophosphate in membranes depend on the transmembrane
electrical potential. The electron micrographs indicate that polyprenyl
monophosphates with single isoprenyl chains form lipid vesicular bilayers. The
thickness of the bilayer, evaluated from the micrographs, was 11 +/- 1 nm. This
property creates possibility of forming primitive bilayer lipid membranes by long
single-chain polyprenyl phosphates in abiotic conditions. It can be the next step
in understanding the origin of protocells.
PMID- 11014865
TI - Enhanced degradation of hexachlorocyclohexane isomers by Sphingomonas
paucimobilis.
AB - Hexachlorocyclohexane (HCH) has been banned for use in technologically advanced
countries; however, it is still in use in tropical countries like India. Earlier
we reported the degradation of HCH isomers by Sphingomonas paucimobilis within 12
days of incubation. Here we report the role of different factors that could
enhance the degradation rate of HCH isomers. We found that an increase in the
cell number from 10(2) to 10(8) cells/ml resulted in an increased degradation
rate of HCH isomers viz. alpha, beta, gamma, and delta-HCH. While alpha-HCH and
gamma-HCH disappeared completely from the medium within 3 days of incubation, a
maximum of only 90% and 85% degradation was observed for beta and delta-HCH,
respectively. We have also observed that adapted cultures degraded HCH isomers
more efficiently than did the normal cultures.
PMID- 11014867
TI - Comparison of 2,4,6-trinitrotoluene degradation by seven strains of white rot
fungi.
AB - The degradation of 2,4,6-trinitrotoluene (TNT) by seven strains of white rot
fungi was examined in two different media containing 50 mg L(-1) of TNT. When TNT
was added into a nutrient-rich YMG medium at the beginning of the incubation,
four of the fungal strains completely removed TNT during several days of
incubation and showed higher removal rates than those of Phanerochaete
chrysosporium. TNT added into YMG medium after a 5-day preincubation period
completely disappeared within 12 hours, and the removal rates were higher than
those in N-limited minimal medium. Isomers of hydroxylamino-dinitrotoluene were
identified as the first detectable metabolites of TNT. These were transformed to
amino-dinitrotoluenes, which also disappeared during further incubation from
cultures of Irpex lacteus. During the initial phase of TNT degradation by I.
lacteus, dinitrotoluenes were also detected after the transient formation of a
hydride-Meisenheimer complex, indicating that I. lacteus used two different
pathways of TNT degradation simultaneously.
PMID- 11014866
TI - Cloning, sequencing, and function of sanF: A gene involved in nikkomycin
biosynthesis of Streptomyces ansochromogenes.
AB - A 111-bp DNA fragment related to nikkomycin biosynthesis of Streptomyces
ansochromogenes 7100 was obtained with the method of reverse genetics. Then, a
2.2-kb DNA fragment was cloned from the DNA library of S. ansochromogenes 7100 by
using the 111-bp fragment as a probe. Sequence analysis showed that the fragment
contains one complete open reading frame (ORF) that encodes a 219-amino acid (aa)
protein, and this gene was designated sanF (GenBank Accession No. AF223971). The
function of the sanF gene was studied by a strategy of gene disruption, and the
resulting sanF mutants lost the ability to synthesize biologically active
nikkomycin, indicating that sanF is essential for nikkomycin biosynthesis.
PMID- 11014868
TI - Isolation and characterization of the thylakoid membranes from the NaCl-resistant
(NaCl(r)) mutant strain of the cyanobacterium Anabaena variabilis.
AB - NaCl-induced changes in the thylakoid membrane of wild-type Anabaena variabilis
and its NaCl(r) mutant strain have been studied. Biochemical characterization of
the thylakoid membrane was done by taking its absorption and fluorescence spectra
at different wavelength. The thylakoid membranes of both strains were isolated by
mechanical disruption of the freeze-dried and lysozyme-treated cells, followed by
differential and density gradient centrifugation. The light absorption spectra of
the thylakoid membrane showed three and two peaks in NaCl(r) mutant strain and
its wild-type counterpart respectively at wavelengths of 400-850 nm. These peaks
revealed that the thylakoid membrane contains a large amount of carotenoid and
chlorophyll a. Fluorescence emission spectra of thylakoid membrane of NaCl(r)
mutant and its wild-type strain at excitation wavelength of 335 nm showed two
different peaks, one at 340 nm and the other at 663 nm respectively. The light
absorption and fluorescence spectra of the thylakoid membrane also revealed that
the membrane contained carotenoid pigment, chlorophyll (Chl) a, and a pigment
with an emission peak at 335 nm. The HPLC analysis of the pigments of the
thylakoid membrane indicates that the NaCl(r) mutant strain under NaCl stress
contained an additional peak for the carotenoid pigment, which was lacking in its
wild-type counterpart. The major peak in thylakoid membrane was that of
echinenone and beta-carotene. Whereas the polypeptide composition of thylakoid
membrane differed in the wild-type and its NaCl(r) mutant strain, no difference
in the cell wall protein pattern was observed in both strains. The thylakoid
membrane of NaCl(r) mutant strain contained two additional protein bands that
were absent in its wild-type counterpart. The thylakoid membrane of the wild-type
and its NaCl(r) mutant strain also showed morphological variations under NaCl
stress.
PMID- 11014869
TI - Temperature elevation regulates iron protoporphyrin IX and hemoglobin binding by
Porphyromonas gingivalis.
AB - Porphyromonas gingivalis, an obligate anerobe with a growth requirement for iron
protoporphyrin IX (FePPIX), is exposed to increased temperatures in the inflamed
periodontal pocket. In this study, P. gingivalis was grown in a chemostat at 37
degrees C (control), 39 degrees C, and 41 degrees C, and examined for
hemagglutinating (HA) activity, hemoglobin binding and degrading activity, and
iron protoporphyrin IX binding. HA activity decreased in cells as the growth
temperature increased. Binding of mu-oxo bishaem (dimeric haem), and Fe(II)- and
Fe(III)-monomeric forms was increased in 39 degrees C-grown cells but decreased
in 41 degrees C-grown cells compared with controls. Cellular hemoglobin binding
and degradation decreased with increased growth temperature. The decrease in
cellular hemagglutination and hemoglobin degradation occurring with increased
growth temperature would limit the potential overproduction of toxic monomeric
haem molecules. The increased binding of mu-oxo bishaem and monomeric forms of
FePPIX at 39 degrees C may reflect a defense strategy against reactive oxidants
and a mechanism of dampening down the inflammatory response to maintain an
ecological balance.
PMID- 11014870
TI - Effects of thymol on ruminal microorganisms.
AB - Thymol (5-methyl-2-isopropylphenol) is a phenolic compound that is used to
inhibit oral bacteria. Because little is known regarding the effects of this
compound on ruminal microorganisms, the objective of this study was to determine
the effects of thymol on growth and lactate production by the ruminal bacteria
Streptococcus bovis JB1 and Selenomonas ruminantium HD4. In addition, the effect
of thymol on the in vitro fermentation of glucose by mixed ruminal microorganisms
was investigated. Neither 45 nor 90 microg/ml of thymol had any significant
effect on growth or lactate production by S. bovis JB1, but 180 microg/ml of
thymol completely inhibited growth and lactate production. In the case of S.
ruminantium HD4, 45 microg/ml of thymol had little effect on growth and lactate
production; however, 90 microg/ml of thymol completely inhibited growth of S.
ruminantium HD4. Thymol also decreased glucose uptake by whole cells of both
bacteria. When mixed ruminal microorganisms were incubated in medium that
contained glucose, 400 microg/ml of thymol increased final pH and the acetate to
propionate ratio and decreased concentrations of methane, acetate, propionate,
and lactate. In conclusion, thymol was a potent inhibitor of glucose fermentation
by S. bovis JB1 and S. ruminantium HD4. Even though thymol treatment decreased
methane and lactate concentrations and increased final pH in mixed ruminal
microorganism fermentations of glucose, concentrations of acetate and propionate
were also reduced.
PMID- 11014871
TI - Evaluation of phospholipid and fatty acid compositions as chemotaxonomic markers
of Alteromonas-like proteobacteria.
AB - The cellular phospholipids (PLs) and fatty acids (FAs) were investigated in type
and environmental strains of Pseudoalteromonas, Alteromonas macleodii, A.
infernus, and in three type strains of Marinomonas, M. communis, M. vaga, M.
mediterranea. A total of 40 strains (19 strains in this study and 21 reported in
previous papers), including Idiomarina abyssalis, I. zobellii, and Glaciecola
punicea, G. pallidula, aerobic Alteromonas-like proteobacteria showed genus
characteristic patterns of phospholipids and fatty acids useful for genera
discrimination. The PL patterns of surface cultures of alteromonads,
pseudoalteromonads, and marinomonads consisted almost entirely of phosphatidyl
ethanolamine and phosphatidyl glycerol presented in different proportions.
Neither diphosphatidyl glycerol nor glycophospholipids were found in bacteria
studied. In addition, the minor amount of a glycolipid was found in all strains
studied. Bacteria of the genera Marinomonas, Idiomarina, and Glaciecola were
clearly distinguished by presence of one of the major FAs: 18:1 (n-7), i15:0, and
16:1 (n-7), respectively. The amounts of these FAs reached up to 40-60% of total
FAs. Members of Alteromonas and Pseudoalteromonas were characterized by different
ratio of the following major FAs:16:1(n-7), 16:0, 17:1 (n-8), and 18:1 (n-7).
PMID- 11014872
TI - Occurrence of multiple ribonucleotide reductase classes in gamma-proteobacteria
species.
AB - Ribonucleotide reductase (RNR) is central to de novo synthesis of
deoxyribonucleotides and essential for all living cells. Three classes have been
described; class I is oxygen dependent and represented by two subclasses, Ia
(NrdAB) and Ib (NrdEF); class II (NrdJ) is indifferent to oxygen; and class III
(NrdDG) is oxygen sensitive. More than one class can be found in an organism,
reflecting the oxygen status of its environment. We have investigated, by using
PCR and Southern blot, the occurrence of the different classes among species of
the gamma-Proteobacteria. Class III are present in all species tested, but the
presence of the other classes varies. Some species contain one unique additional
enzyme, class Ia, Ib, or II, whereas others contain two additional enzymes, class
Ia and Ib, or class Ia and II.
PMID- 11014873
TI - Analysis of expression of the binary toxin genes from Bacillus sphaericus in
Anabaena and the potential in mosquito control.
AB - Anabaena strains expressing the binary toxin genes of Bacillus sphaericus produce
high larvicidal activity with living cells. Western blot analysis showed that the
51-kDa and 42-kDa toxin proteins were stable in Anabaena. When a DNA fragment
upstream of the 51-kDa protein gene was deleted, the toxicity was reduced by over
a hundred-fold, whereas deletions at the coding regions showed that the
cooperation of the two proteins expressed in Anabaena is essential for the
larvicidal activity. Outdoor tests showed that the genetically altered Anabaena
could keep containers with natural water from being inhabited by Culex larvae for
over 2 months.
PMID- 11014874
TI - Internal glutamine and glutamate pools in Klebsiella pneumoniae grown under
different conditions of nitrogen availability.
AB - Internal pool sizes of glutamine and glutamate in Klebsiella pneumoniae grown
under nitrogen limitation or nitrogen sufficiency were measured to study the
signal transduction of external nitrogen limitation. K. pneumoniae cells were
grown in an anaerobic, ammonium-limited chemostat culture. At a growth rate of
0.217 h(-1), the steady state ammonium concentration in the culture was 55
microm, correlating with repression of the nitrogen fixation (nif) genes. At
growth rates below 0.138 h(-1), the ammonium concentration in the culture dropped
below 0.5 microm and the nif genes became derepressed. During the transition from
nitrogen sufficiency to nitrogen limitation, the internal glutamine pool in K.
pneumoniae decreased by a factor of approximately 6. The glutamate pool, however,
remained stable. Similarly, in anaerobic batch cultures with different limiting
nitrogen sources, the glutamine pool generally decreased by a factor of 7 to 9
when nif gene derepression was achieved. All the limiting nitrogen sources used
resulted in decreased growth rates compared with growth under nitrogen excess,
suggesting an inverse relationship between glutamine pool size and doubling time.
These studies indicate that K. pneumoniae perceives external nitrogen limitation
as internal glutamine limitation.
PMID- 11014875
TI - Potassium and sodium fluxes in the phytopathogenic fungus Fusarium oxysporum var.
lini.
AB - Rubidium uptake in potassium-starved cells followed biphasic kinetics in the
micromolar and millimolar range and was independent of the temperature. In
contrast, Rb(+) uptake in normal-K(+) cells followed a monophasic kinetics in the
millimolar range and increased at temperatures higher than 30 degrees C.
Differences in the K(m) values and in the Arrhenius plots of Rb(+) uptake suggest
different uptake systems in K(+)-starved and in normal-K(+) cells. In addition,
the substantial inhibition of Rb(+) uptake caused by carbonyl cyanide-m
chlorophenyl hydrazone indicates that these systems are strongly dependent on
membrane voltage. Lithium (sodium) tolerance, influx, and efflux were separately
studied. F. oxysporum was shown to be very tolerant to sodium, while lithium
caused a specific toxic effect. Li(+) uptake in K(+)-starved cells exhibits a
monophasic kinetics with low affinity. Li(+) efflux was not affected by external
pH or addition of potassium to the medium, suggesting that a Na(+)/cation
antiporter is not involved in this process.
PMID- 11014876
TI - Calcium and phosphate regulation of nitrogen metabolism in the cyanobacterium
Spirulina platensis under the high light stress.
AB - High light stress (40 W/m(2))-induced alterations in the nitrogen assimilatory
enzymes in Spirulina platensis were studied under the Ca(2+) and phosphate (Pi)
supplemented as well as starved conditions. Results revealed that activities of
nitrate reductase (NR), amino acid transferases (AST/GOT and ALT/GPT), and
protease enzymes in the high-light-incubated cells were relatively higher under
the Ca(2+)- and Pi-starved conditions. On the contrary, relative rates of
glutamine synthetase (GS) and ATPase activities were lower in the Ca(2+)- and Pi
starved cells. But the Spirulina cells under the Ca(2+)- and Pi-added conditions
showed enhanced activity of both GS and ATPase enzymes. During the high-light
stress, a decline in the GS activity, particularly under the Ca(2+)- and Pi
starved conditions, was indicative of a nitrogen starvation-like condition. This
could be one of the reasons for induction of the NR and protease enzymes. A
higher rate of GS activity was recorded under both the Ca(2+)- and Pi
supplemented conditions, perhaps owing to the enhanced rate of ATPase activity in
such conditions. But a declining pattern of both NR and protease activities in
the presence of Ca(2+) and Pi, despite the higher rate of ATPase activity, might
involve some other mechanism like the protein-kinase system.
PMID- 11014877
TI - A comparison of Legionella pneumophila occurrence in hot water tanks and
instantaneous devices in domestic, nosocomial, and community environments.
AB - The aim of this study was to compare the occurrence of L. pneumophila in hot
water samples from hot water tanks and instantaneous devices. Tanks and devices
were all operated by heat exchangers employed in the town's district heating
system. Thirty-six out of 171 (21%) hot water samples tested positive for L.
pneumophila isolation, with 14.6% belonging to serogroup 1 and 6.4% to serogroups
2-14. The proportion of L. pneumophila detected in hot water reservoirs (30%) was
higher than that observed in hot water instantaneous devices (6.2%). Differences
in L. pneumophila isolation reflected different temperatures registered at the
faucet: =50 degrees C for hot water from reservoir devices, and >60 degrees C
for hot water from instantaneous devices. These data emphasize the need to
control temperature in hot water distribution devices, thus inhibiting the
formation of biofilm and L. pneumophila colonization.
PMID- 11014878
TI - Kinematic analysis of laryngeal movements in patients with neurogenic dysphagia
before and after swallowing rehabilitation.
AB - To examine whether kinematic analysis of laryngeal movements (which are closely
linked to pharyngeal swallowing) can differentiate between normal and disturbed
swallowing, we used a three-dimensional ultrasound movement recording system to
measure the movements of the larynx during swallowing in 32 patients with
neurogenic dysphagia caused by central nervous system lesions and in 32 age- and
sex-matched healthy individuals. At the beginning of an inpatient rehabilitation
swallowing program, laryngeal movements in 24 patients were highly disturbed in
terms of velocity curve irregularities. After rehabilitation, the majority of
patients with hitherto irregular velocity profiles exhibited laryngeal kinematics
that were indistinguishable from those of 32 healthy subjects. Kinematic analysis
of laryngeal movements, therefore, is suitable for monitoring motor recovery of
swallowing disturbances in patients with neurogenic dysphagia while undergoing
swallowing rehabilitation.
PMID- 11014879
TI - Effectiveness of four hours of education in interpretation of radiographic
studies.
AB - Clinicians working with oropharyngeal swallowing disorders often use
videofluoroscopy to define their patients' swallowing abnormalities. This study
examined the effect of 4 hours of training in the identification of head and neck
anatomy and oropharyngeal swallowing disorders viewed radiographically. Ninety
clinicians participated in a 5-hour session which included 30-minute pre- and
post-tests requiring identification of head and neck anatomy and oropharyngeal
swallowing disorders and a 4-hour training period. Results showed significant
improvement in identification of both radiographic anatomy and swallowing
disorders. The change in pre- and post-test measures was negatively correlated
with extent of prior experience in dysphagia. Similar studies are needed with
clinicians or students inexperienced in dysphagia to define the number of hours
of education needed in order for students to reach a desired accuracy level in
their identifications.
PMID- 11014880
TI - Prevalence of aspiration and laryngeal penetration in patients with unilateral
vocal fold motion impairment.
AB - The adverse consequences of aspiration in regard to patient health and quality of
life are well documented. It is generally accepted that the probability of
aspiration is increased in patients with unilateral vocal fold motion impairment,
however, the incidence and proposed mechanism of aspiration vary depending on the
reported series. We reviewed the cine or video pharyngoesophagographic findings
in patients with documented unilateral vocal fold motion impairment, identified
through the Johns Hopkins Hospital Swallowing Center database, to determine the
prevalence and cause of aspiration and laryngeal penetration. Aspiration and
laryngeal penetration were identified in 38% and 12% of patients, respectively.
Aspiration resulted from impaired airway protection, not from esophageal
obstruction with laryngeal "spill-over." The number and degree of impairments
directly correlated with probability of aspiration. Obstruction potentiated the
likelihood of aspiration. Video pharyngoesophagography accurately identifies
patients at risk for aspiration.
PMID- 11014881
TI - How thick is thick? Multicenter study of the rheological and material property
characteristics of mealtime fluids and videofluoroscopy fluids.
AB - Objective rheological assessment of fluids given to dysphagic patients at
mealtime and during videofluoroscopy was carried out using a multicenter format.
Thin, quarter-thick, half-thick and full-thick fluids were examined for the
degree of correlation between mealtime fluids and their allegedly matched
videofluoroscopy counterparts. The study was carried out to determine whether
perceived subjective differences between mealtime fluids and videofluoroscopy
fluids could be quantified using the rheological parameters of viscosity,
density, and yield stress. The results showed poor correlation between mealtime
fluids and videofluoroscopy fluids over all parameters. In general, the
videofluoroscopy fluids were more viscous, more dense, and showed higher yield
stress values than their mealtime counterparts. Given these results, it is
reasonable to assume that the fluids used during videofluoroscopy do not provide
an accurate indication of swallowing ability at mealtime. Therefore, it is
suggested that clinicians use objective methods to rheologically match
videofluoroscopy fluids to mealtime fluids.
PMID- 11014882
TI - Use of arterial oxygen saturation, heart rate, and blood pressure as indirect
objective physiologic markers to predict aspiration.
AB - If an indirect bedside variable can reliably predict whether an objective
instrumental dysphagia evaluation is needed, time and money can be saved without
compromising patient care. To date, the search for a reliable indirect subjective
marker of aspiration has not been successful. However, research on indirect
objective markers of aspiration is alluring. The purpose of the present study was
to investigate changes, if any, in the physiologic parameters of arterial oxygen
saturation (SpO(2)), heart rate, and blood pressure during simultaneous objective
confirmation of aspiration status with Fiberoptic Endoscopic Evaluation of
Swallowing (FEES). Sixty adult subjects were divided into 4 groups of 15. Group 1
did not require supplemental oxygen and did not aspirate. Group 2 did not require
supplemental oxygen and exhibited aspiration. Group 3 required supplemental
oxygen and did not aspirate. Group 4 required supplemental oxygen and exhibited
aspiration. Simultaneous SpO(2), heart rate, and blood pressure measurements were
collected at 1-min intervals, i.e., pre-FEES baseline for 5 min; during FEES; and
post-FEES for 5 min. Results indicated no significant differences in SpO(2)
levels based on aspiration status or oxygen requirements for any of the 4 groups.
A consistent pattern of higher heart rate values during FEES and continuing for 5
min post-FEES was observed for all 4 groups. A consistent pattern of higher blood
pressure values during FEES and then lower blood pressure values post-FEES was
observed for all 4 groups. It was concluded that the use of changes in SpO(2),
heart rate, or blood pressure values as indirect objective markers of aspiration
was not supported.
PMID- 11014883
TI - Swallowing physiology of toddlers with long-term tracheostomies: a preliminary
study.
AB - This study investigated the swallowing physiology of toddler-aged patients with
long-term tracheostomies. Structural movements and motility of the pharyngeal
stage of swallowing were studied in four toddlers ranging in age from 1:2
(years:months) to 2:9 with long-term tracheostomies. A patient aged 1:2 years
with no tracheostomy served as a toddler model for comparison. Videofluoroscopic
recordings of the patients' liquid and puree bolus swallows were analyzed for a)
onset times for pharyngeal stage events, laryngeal vestibule closure, and
tracheostomy tube movement; b) timeliness of swallow response initiation; and c)
pharyngeal transport function. Results found differences in timing of pharyngeal
stage movements between the tracheostomized patients and the patient with no
tracheostomy. Laryngeal vestibule closure occurred before or within the same
0.033-s video frame as onset of upper esophageal sphincter (UES) opening in the
patient with no tracheostomy, but occurred 0.033-.099 s after onset of UES
opening in the tracheostomized patients. The time line required to close the
laryngeal vestibule once the arytenoids began their anterior movement was longer
in the tracheostomized patients than in the patient with no tracheostomy and was
associated with laryngeal penetration. The patient with no tracheostomy displayed
superior excursion of the arytenoid and epiglottis during the swallowing; the
tracheostomized patients did not. No association was found between onset of
tracheostomy tube movement and laryngeal vestibule closure. Delayed swallow
response initiation was observed across tracheostomized patients at a mean
frequency of 45% with associated penetration. Pharyngeal dysmotility was not
observed. Findings supported the concept that long-term tracheostomy in toddler
aged patients affects swallowing physiology.
PMID- 11014884
TI - Effects of consistent food presentation on oral-motor skill acquisition in
children with severe neurological impairment.
AB - The purpose of this study was to evaluate systematically the effect of presenting
food consistently, in a position regarded as optimal, to children with severe
neurological impairment who have associated oral-motor dysfunction. We tested the
validity of some recommendations often made in the literature regarding good
feeding practices. The trial used an ABA within-subjects design and extended over
a 9-month period. Sixteen children between 7 and 17 years of age with severe
neurological impairment and associated eating difficulties were studied. Six
subjects had some speech. The effects of the intervention were compared by
detailed analysis of standard feeding assessments carried out and video-recorded
under control and experimental conditions. Statistically significant differences
in components of oral-motor behavior were found when a consistent method of food
presentation was employed and significant improvements, which could not be
attributed to maturation alone, were found between assessment periods. There were
also significant differences in the degree of oral-motor learning achieved by
children who had some speech and those who had none. Newly acquired skills were
not always evident at followup, however, nor in control assessments of feeding.
We conclude that some children, even those with severe neurological impairment,
can acquire mastery over latent or previously undeveloped oral-motor skills when
feeding strategies are modified to allow appropriate opportunities for learning
to occur.
PMID- 11014885
TI - Regarding "Effects of consistent food presentation on oral-motor skill
acquisition in children with severe neurological impairment" (Dysphagia 15:213
223, 2000)
PMID- 11014886
TI - "Whole body" mobility after one year of intraoral appliance therapy in children
with cerebral palsy and moderate eating impairment.
AB - The reciprocal influence of body postures on the oral structures, but also of the
oral structures on body postures, has been proposed by clinicians and is taken
into consideration when treating children with poor postural control and moderate
to severe eating impairments. However, this relationship has not been rigorously
investigated. The purpose of this study was to document the possible
relationships among oral-motor, postural, and ambulatory control. Ambulatory
skills [exclusive use of wheelchair (w/c) vs w/c and ambulation], postural
control when sitting, "pathologic" reflexes, and lip and tongue posture were
recorded before and after one year of therapy with an intraoral appliance (ISMAR)
in 20 children with cerebral palsy and moderate eating impairment. Significant
improvement occurred in sitting (head-trunk-foot control) following one year of
ISMAR therapy. Ambulatory status also significantly improved above the level of
maturation. Half of the children showed marked improvement in oral posture, i.e.,
their resting mouth posture was closed rather than open. These results support an
hypothesis of interaction between oral structures and postural control of the
"whole body." Further studies are needed to determine the controls of such a
relationship.
PMID- 11014887
TI - Assessment of ingestive and oral praxis skills: children with cerebral palsy vs.
controls.
AB - Eating impairments (dysphagia) in children with cerebral palsy (CP) have been
well documented. However, individual components of ingestion, such as the feeding
skills of eating and drinking and their relationship to oral-motor planning
skills (praxis), remain largely undetermined. The purpose of the present study
was to examine functional feeding and oral praxis skills in a group of children
with CP and mild eating impairment and to compare their skills with a group of
age-matched controls. As well, interobserver reliabilities and concurrent
validity of these tests were examined to determine their reliability and to what
extent they may be measuring similar constructs. Twenty-seven children with CP
and 21 age-matched controls, aged 4.0-16 years, participated in this study. Two
oral praxis tests (OFMF and OPT) and two standard ingestive skills tests (GVA and
FFAm) were administered to each child. Children with CP scored consistently and
significantly lower on the OFMF than controls (p < 0.001); similar results were
achieved on the OPT (p < 0.001). Children with CP had difficulty with items where
there was a high demand for repetition and smooth sequencing. On the ingestive
skills tests children with CP took significantly longer for chewing a hard solid
food texture than controls (p < 0.001), and functional feeding skills were also
significantly poorer than in controls. Interrater reliability coefficients for
the OPT and OFMF were excellent (all ICCs > 0.90). There was high concurrent
validity between the OPT and OFMF (r = 0.90, p < 0.0001). The correlations for
the FFAm and GVA tests were somewhat weaker (r = -0.54, p < 0. 0001).
Correlations were negative; as functional feeding scores increased (improved),
chewing time decreased (improved). Excellent reliable and valid assessment
instruments are available to the practicing clinician. They cover a wide range of
oral-motor performance and, so, must be used judiciously and for the purpose that
they have been developed.
PMID- 11014889
TI - A comment on "Prevalence of aspiration and laryngeal penetration in patients with
unilateral vocal fold motion impairment" (Dysphagia 15:184-187, 2000).
PMID- 11014891
TI - Neutropenia accompanying parvovirus B19 infection after gynecologic surgery.
AB - The hematologic data and symptoms of 7 patients seropositive for parvovirus B19
IgM antibody after gynecologic surgery were analysed. Parvovirus may have been
transmitted by fibrin glue prepared from heat-treated human plasma and used for
hemostasis during surgery. The peripheral blood neutrophil count decreased to
below 1 x 10(9)/l between postoperative day (POD) 10 and 18, but recovered
spontaneously to within the normal range. G-CSF injection was effective in
preventing neutropenia or obtaining a prompt recovery. The reticulocyte count
fell below 10 x 10(9)/l between POD 13 and 19, and also recovered spontaneously.
A slapped-cheek rash was not observed in any of the 7 patients.
PMID- 11014890
TI - Expression of wild-type p53 and Bcl-2 family genes oscillates with recurrent
remission and relapse in an unusual case of low-grade lymphoma.
AB - Downregulation of apoptosis has been proposed as a mechanism of clonal expansion
in low-grade B cell neoplasms. We have previously described an unusual case of
CD5+ B cell lymphoma characterized by cycles of leukemic phase alternating with
spontaneous remission. In the present study, we examined the involvement of
apoptosis-related proteins in the progression of this cyclic lymphoma ex vivo.
During the leukemic phases, the clonal cells were activated blasts expressing
elevated levels of wild-type (wt) p53, Bcl-2, Bcl-x(L), and Bax, while Bak
expression increased during the decline of lymphocytosis. Bax heterodimerized
with Bcl-2 but not with Bcl-x(L). The anti-apoptotic Bcl-2/Bax heterodimers
peaked during early leukemic phases and declined during regression. The elevation
in Bcl-2, Bcl-x(L) and Bax expression during early leukemic phases seems to
result from cell activation since a similar increase was induced by activating
the remission phase leukemic cells in culture. The data suggest that wt p53, Bcl
x(L), and Bcl-2/Bax heterodimers support the accumulation of activated leukemic
cells during the leukemic phases, while Bax and Bak may be involved in their
decline during regression.
PMID- 11014892
TI - Prevalence of the C677T methylenetetra- hydrofolate reductase mutation in Thai
patients with deep vein thrombosis.
AB - We investigated the prevalence of a genetic variation in the 5, 10
methylenetetrahydrofolate reductase (MTHFR) gene (C677T) using polymerase chain
reaction techniques in a sample of 500 general Thai population and among 40
unselected Thai patients with an objectively confirmed history of deep vein
thrombosis (DVT). The prevalence of the mutated homozygous and heterozygous C677T
MTHFR genotype in the group of 500 healthy Thai population was 1.4 and 25.6%,
respectively (allele frequency of 14.2%). Of the 40 patients studied, none were
homozygotes and 15% were heterozygotes for the C677T MTHFR gene mutation (allele
frequency of 7.5%). There was no significant difference in genotype frequency
between patients and control groups (p = 0.09). Odds ratios for the probability
of the C677T MTHFR gene mutation in the patient versus control group were 0.49
(95% CI 0. 21-1.12). These data indicated that the C677T MTHF gene mutation was
not associated with DVT in the Thai population. The lower frequency of the C677T
MTHFR gene mutation in our Thai population compared with reports from other
studies suggests a wide heterogeneity in the 677T MTHFR genotype frequencies of
the different ethnic populations even among Asians.
PMID- 11014893
TI - Th1 and Th2 cytokine profiles in sickle cell disease.
AB - We have investigated the levels of Th1 (IL-2 and IFN-gamma) and Th2 (IL-4)
cytokines in the plasma and supernatants following peripheral blood mononuclear
cell culture and mitogen stimulation in a group of 39 patients with sickle cell
disease (SCD) made up of 29 SS, 8 Sbeta-thal and 2 Hb SD in steady state. Five SS
patients were studied during 7 episodes of vaso-occlusive crisis. Twenty-four
control (3 Hb AS and 21 Hb AA) were also studied; 10 were acutely ill while 14
were healthy at the time of the study. The plasma levels of IL-2 and IFN-gamma
were similar in the patients and the controls. However, plasma IL-4 was
significantly higher among the steady-state SS patients than in the controls.
While there was no significant difference in cytokine levels following mitogen
stimulation in the different groups, plasma IL-2 to IL-4 and IFN-gamma to IL-4
ratios were significantly lower among the steady-state SS patients, indicating a
possible Th2 bias in our sickle cell patients and suggesting a possible mechanism
to explain the predisposition of SCD patients to bacterial infections. However,
SS patients with good splenic function showed a relative Th1 bias, which may be
an additional explanation for the protection against bacterial infections in such
patients.
PMID- 11014895
TI - Trisomy 14 with thrombocytosis and monocytosis.
AB - It has been reported that trisomy 14 is associated with myeloid malignancies, but
a case with increased platelet count has also been reported. However, the
clinical significance of trisomy 14 is still uncertain. We report a patient with
trisomy 14 with thrombocytosis and a gradual increase in monocytosis. He was
treated with hydroxyurea, cytarabine and aclarubicin in low doses and his quality
of life was maintained for a period of about 1 year from blastic crisis.
Hydroxyurea, cytarabine or aclarubicin in low doses may be the treatment of
choice for trisomy 14 patients with respect to the patients' quality of life.
PMID- 11014894
TI - New imaging findings in a patient with central nervous system dysfunction after
bone marrow transplantation.
AB - Central nervous system disorders are an important complication of bone marrow
transplantation (BMT). We have recently performed cerebral angiography to examine
central nervous system dysfunction in a 22-year-old woman with acute
lymphoblastic leukaemia who had undergone BMT. Angiography demonstrated multiple
stenoses and occlusions in the peripheral branches of the anterior and middle
cerebral arteries, a pattern similar to that seen in vasculitis. She was thought
to most likely have cytomegalovirus (CMV) vasculitis, but other forms of
vasculitis, such as angiitis-like-syndrome-associated graft-versus-host disease
could not be excluded. This case suggests that CMV vasculitis may cause central
nervous system dysfunction after BMT and that imaging studies may provide useful
information about central nervous system disorders in these patients.
PMID- 11014896
TI - CD5+ immunophenotype in the bone marrow but not in the peripheral blood in a
patient with hairy cell leukemia.
AB - We report the case of a patient with rare CD5+ hairy cell leukemia, which was
unusual, as there was also a discrepancy between the bone marrow and peripheral
blood immunophenotypes. We propose that some degree of maturation within the
malignant clone and the predominance of more mature CD5- hairy cells in the
peripheral blood can explain this observation. The patient was treated with a
conventional course of cladribine (2'-chlorodeoxyadenosine) and achieved complete
remission. We conclude that the unusual CD5+ immunophenotype of this patient did
not affect prognosis or change the response to standard therapy.
PMID- 11014897
TI - ALK-negative anaplastic large cell lymphoma and Hodgkin's disease of nodular
sclerosing type in 2 siblings.
AB - Familial clustering of Hodgkin's disease (HD) and increased risk of developing
the disease among the siblings of affected patients suggest that both
environmental and genetic factors may play an important role in its pathogenesis.
An association between Epstein-Barr virus (EBV) and HD has been widely
demonstrated. Recently, latent membrane protein of EBV has also been detected in
CD30-positive anaplastic large cell lymphoma. Familial aggregation of HD and a
three- to seven-fold-increased risk among the siblings of affected patients
suggest increased genetically determined susceptibility. No data about genetic
factors are available for anaplastic large-cell lymphoma. In this study, the
authors report the case of a woman with anaplastic-lymphoma-kinase (ALK)-negative
CD30-positive anaplastic large cell lymphoma, whose brother had developed HD 11
years previously. The clinical, histologic, and immunohistochemical features of
the 2 lymphomas were studied. Both siblings showed bulky mediastinal involvement,
effacement of normal lymph node architecture by large, atypical cells, resembling
Reed-Sternberg cells, expression of EBV latent membrane protein-1 in the lymph
node specimens, concordance of both HLA classes I and II. The clinical
presentations and immunological studies disclose numerous similarities between
the 2 cases and can suggest that their association is not fortuitous. At present,
in problematic cases, a combination of morphologic, immunophenotypic and genetic
studies may contribute to better define the tumour type.
PMID- 11014898
TI - Acute promyelocytic leukemia with marrow fibrosis at initial presentation:
possible involvement of transforming growth factor-beta(1).
AB - Although the occurrence of marrow fibrosis in acute myeloid leukemia has been
described, there have been no reports of acute promyelocytic leukemia (APL)
associated with marrow fibrosis. Here we describe an APL patient with severe
marrow fibrosis at initial presentation. He had the typical manifestations of
APL, except for marrow fibrosis. Complete remission was achieved by treatment
with all-trans retinoic acid plus chemotherapy, and his marrow fibrosis gradually
improved concomitantly with the decrease in leukemic cells. To clarify the
mechanism of marrow fibrosis in this patient, we investigated the expression of
genes for several cytokines promoting fibrosis by the reverse transcriptase
polymerase chain reaction methods. An overexpression of transforming growth
factor-beta(1) was noted in his leukemic cells at initial presentation, whereas
no increase in expression was observed at the time of relapse when he no longer
had marrow fibrosis. These findings suggest that overexpression of transforming
growth factor-beta(1) was involved in the development of marrow fibrosis in this
APL patient.
PMID- 11014899
TI - Plasmodium falciparum malaria infection complicated by haemophagocytic syndrome
in an old man.
PMID- 11014900
TI - Complete blood cell counts in capillary and venous blood of healthy term
newborns.
PMID- 11014901
TI - wt1 gene expression in childhood acute leukemias.
PMID- 11014902
TI - Socio-economic and behavioural risk factors for tooth loss from age 18 to 26
among participants in the Dunedin Multidisciplinary Health and Development Study.
AB - OBJECTIVE: To determine the risk factors associated with tooth loss between the
ages of 18 and 26. METHODS: Dental examinations at ages 18 and 26 were conducted
on Study members in the Dunedin Multidisciplinary Health and Development Study,
and sociodemographic and dental service use data were collected using a self
report questionnaire. At age 15, an estimate of socio-economic status (SES) for
each Study member had been obtained by classifying the occupation of the male
parent. A case of tooth loss was defined as an individual who had lost one or
more teeth (excluding third molars) due to caries between ages 18 and 26.
Logistic regression and Poisson analysis were used to model the occurrence of
tooth loss. RESULTS: Among the 821 study members who were examined at both ages,
one or more teeth were lost because of caries by 85 (10.3%). After controlling
for sex, SES and visiting pattern, baseline caries experience predicted
subsequent tooth loss, with the odds increasing by 2.8 for every increase by 1 in
the number of decayed surfaces present at age 18. Episodic dental visitors had
3.1 times the odds of their routine visiting counterparts of losing a tooth over
the observation period. The number of teeth lost was, on average, 2.3 times
higher among episodic dental visitors. CONCLUSIONS: Socio-economic inequalities
in tooth loss appear to begin early in the life course, and are modified by
individuals' SES and dental visiting patterns.
PMID- 11014903
TI - Twenty-four month coronal caries incidence: the role of dental care and race.
AB - OBJECTIVES: To describe for a diverse sample of dentate middle-aged and older
adults: (1) the 24-month incidence of coronal caries, and (2) its association
with a broad range of clinical, behavioral, financial, attitudinal, and
sociodemographic factors. METHODS: The Florida Dental Care Study is a prospective
observational longitudinal cohort study of 873 persons who at baseline had at
least 1 tooth and were 45 years or older. In-person interviews and clinical
examinations were conducted at baseline and 24 months, with 6-monthly telephone
interviews between those times. A multinomial logistic regression was done to
predict whether a participant was in one of four mutually exclusive groups at the
24-month examination (new decay only [NDO]; new filling(s) only [NFO]; both new
decay and filling(s) [BOTH]; or neither [NONE]). RESULTS: Only 33% of the 24
month participants were in the NONE group. There was no significant difference in
caries incidence between regular attenders and problem-oriented attenders,
regardless of whether teeth crowned at baseline, incident crowns, or incident
root fragments were excluded. However, once differences in incident tooth loss
and baseline clinical, behavioral, financial, and attitudinal differences were
taken into account, regular attenders did appear to benefit by developing fewer
coronal lesions and fewer dental symptoms than problem-oriented attenders.
Baseline carious surfaces, filled surfaces, number of teeth, and bulk restoration
fractures predicted caries incidence, but baseline cusp fractures did not.
Persons with negative dental attitudes were more likely to be in the NDO and BOTH
groups, and negative attitude toward brushing and flossing (but not their
frequency) also predicted caries incidence. CONCLUSION: Certain baseline clinical
conditions, approach to dental care, ability to pay for dental care, dental
attitudes, race, and age group were predictive of coronal caries incidence, and
regular attenders appeared to benefit from regular attendance.
PMID- 11014904
TI - Caries prediction by multiple salivary mutans streptococcal counts in caries-free
children with different levels of fluoride exposure, oral hygiene and sucrose
intake.
AB - The aims of this study were to assess whether multiple salivary mutans
streptococcal (ms) counts have a higher predictive power than a single one, and
whether the predictive power of the test is different at different levels of
fluoride exposure, oral hygiene and sucrose consumption. Three salivary ms tests
were performed at 3-month intervals (positive test: salivary ms >/=5x10(5)
cfu/ml) on a sample of 304, initially caries-free, 6- to 7-year-olds. Plaque
index was also assessed and the parents filled out a questionnaire concerning
sucrose-containing eating events and fluoride exposure. Sensitivity, specificity
and Youden's index (J) were used to compare the predictive power. Thirty-six
percent of the children developed caries during the 2-year follow-up. The highest
J value for a single ms test (the second) was 0.24 (sensitivity 29.1%,
specificity 95.4%). The multiple ms test with the highest J value (0.29) was
obtained by the dichotomies 0 vs. 1-3 positive tests (sensitivity 50.0%,
specificity 79.9%) and 0-1 vs. 2-3 positive tests (sensitivity 31.8%, specificity
97.4%). The predictive power of the multiple test was passable for children with
low fluoride exposure and high plaque index (sensitivity 57.4%, specificity
93.7%, J 0.51), while it was low for the other groups. Sucrose exposure did not
significantly affect the predictive power of the ms test.sion.
PMID- 11014905
TI - In situ acid resistance of in vivo formed white spot lesions.
AB - Thin sections of natural enamel lesions, so-called white spots (WS), and areas of
sound enamel (SEn) adjacent to the WS were exposed to an intraoral environment
for 2 weeks. Thin sections of WS samples, clamped in a PMMA holder, were
microradiographed before and after exposure to intraoral conditions. Acid
resistance was evaluated by lesion depth and mineral changes during the
cariogenic challenge. The results show that there were statistically significant
differences in lesion depth, mineral loss and mineral volume percent at the
surface before and after the intraoral cariogenic challenge at least at p<0.05,
except for a change in mineral volume percent at the surface of WS samples. This
exception indicates that no mineral change occurred in the surface layer of WS.
The fact of 2.8 and 1.8 times higher ratios of SEn over WS of mean changes in
lesion depth and mineral loss data, respectively, seems to indicate a
quantitative difference in acid resistance level of WS lesions compared with the
areas of SEn. Regarding the site of mineral changes, a distinctive feature of WS
samples is that mineral loss occurs at the bottom of lesions. In contrast, areas
of SEn produce a typical subsurface type of lesions. From this in situ study, it
can be concluded that the surface of WS samples was apparently much more acid
resistant (at least approximately 2 times) than the areas of SEn that received a
similar intraoral acid challenge.
PMID- 11014906
TI - Relationship between mineral distributions in dentine lesions and subsequent
remineralization in vitro.
AB - Though the mineral distribution of the dentine carious lesion varies largely from
tooth to tooth and from patient to patient, there are two main distribution
profiles that characterize natural carious lesions in dentine. These profiles
include softened and subsurface lesion types. The mineral distribution
relationship between the starting profile and the profile after remineralization
is not known. In order to study the relational aspects, we have produced
demineralized dentine samples in vitro with mineral profiles similar to those of
typical natural carious lesions, and subsequently remineralized the samples in a
remineralizing solution with various fluoride concentrations (0, 2 and 10 ppm F).
The mineral distributions were obtained by using an improved microradiographic
technique. In addition, the nature of deposited mineral was analyzed by diamond
coupled total internal reflectance spectroscopy. Definite relationship was
observed between the original lesion mineral distribution and the mineral
distributions following remineralization. The amount of mineral present in
approximately the first 50 microm of the lesion influenced the overall mineral
profile after remineralization, possibly through influencing ion transport. If
the amount was high (> approximately 10 vol%), the deposited mineral was confined
to the surface (0-50 microm). The original mineral at those depths acted like a
nucleus of mineral regrowth when the amount of residual mineral was intermediate,
and like a transport barrier when the surface layer was well mineralized. If a
surface barrier was not present, mineral was deposited at deeper depths in the
lesion. Fluoride effect on dentine remineralization was dependent on the original
mineral content and its distribution in the lesion. Although a high concentration
of fluoride was very effective in low-mineral lesions, it produced
hyperremineralization on well-mineralized subsurface lesions so that it prevented
effective remineralization especially in deeper lesions.
PMID- 11014908
TI - Differences in acidogenicity of S. sobrinus and S. rattus are linked to the
catalytic efficiency of the glycolytic key enzyme phosphofructokinase.
AB - This contribution describes the biochemical properties of two catalytically
different phosphofructokinases (PFKs) purified from Streptococcus rattus LB 2
(PFK-rat) and Streptococcus sobrinus OMZ 65 (PFK-sob), respectively. Steady-state
kinetics revealed K(M) = 0. 8 mM for PFK-rat and K(M) = 0.08 mM for PFK-sob for F
6-P as the substrate. The enzymes also differ in their pH profiles: whereas the
highest activity of PFK-rat was measured at pH = 8.0, the optimum pH of PFK-sob
was at pH = 7.0. In addition, compared to PFK-sob, PFK-rat was more sensitive
against the allosteric inhibitor ATP. PFK catalyzes a committed step of
glycolysis, the main acid producing catabolic pathway. Thus, the catalytically
more efficient enzyme isolated from S. sobrinus OMZ 65, especially at low pH,
could explain the comparably high acidogenicity of this strain.
PMID- 11014907
TI - Fluoride in plaque fluid, plaque, and saliva measured for 2 hours after a sodium
fluoride monofluorophosphate rinse.
AB - Sodium monofluorophosphate (NaMFP) and sodium fluoride (NaF) are the two most
common sources of fluoride used in currently marketed fluoride dentifrices. The
purpose of this study was to investigate the effect of mouth rinses containing
NaF or NaMFP on the concentrations of fluoride, or the MFP ion, in saliva, whole
plaque, and plaque fluid. Twelve subjects abstained from tooth brushing for 48 h,
fasted overnight, and then rinsed 1 min with 12 mmol/l (228 ppm [microg/g] F) NaF
or NaMFP in the morning. Before the rinse and at 30, 60 and 120 min afterwards,
upper and lower molar and premolar plaque samples and whole saliva samples were
collected. Aliquots of plaque fluid and centrifuged saliva were obtained from
these samples, and the whole plaque residue acid extracted. The F and MFP
concentrations were then measured in these samples using ultramicro methods. For
both rinses, a higher concentration of plaque fluid fluoride was found at lower
molar sites while the reverse was true for the whole plaque fluoride.
Furthermore, for both rinses, plaque fluid, whole plaque, but not salivary,
fluoride concentrations were above baseline at 120 min. Following the NaMFP
rinse, a substantial amount of unhydrolyzed MFP was found in plaque fluid and
saliva. Although there was a very large range in these measurements, fluoride in
plaque fluid (excluding fluoride in unhydrolyzed MFP) and whole plaque were
significantly (p<0.05) greater after the NaF rinse at all time periods. In
saliva, the NaF rinse produced a statistically significant greater salivary
fluoride (excluding fluoride in unhydrolyzed MFP) only at 60 min. The lack of a
clear correlation between these measurements and clinical studies suggest a novel
mechanism may enhance the effectiveness of NaMFP dentifrices.
PMID- 11014909
TI - Effects of Apis mellifera propolis on the activities of streptococcal
glucosyltransferases in solution and adsorbed onto saliva-coated hydroxyapatite.
AB - Propolis, a resinous hive product collected by Apis mellifera bees, has been used
for thousands of years in folk medicine. Ethanolic extracts of propolis (EEP)
have been shown to inhibit the activity of a mixture of crude glucosyltransferase
(Gtf) enzymes in solution. These enzymes synthesize glucans from sucrose, which
are important for the formation of pathogenic dental plaque. In the present
study, the effects of propolis from two different regions of Brazil on the
activity of separate, purified Gtf enzymes in solution and on the surface of
saliva-coated hydroxyapatite (sHA) beads were evaluated. The EEP from Minas
Gerais (MG; Southeastern Brazil) and Rio Grande do Sul (RS; Southern Brazil) were
tested for their ability to inhibit the enzymes GtfB (synthesis of insoluble
glucan), GtfC (insoluble/soluble glucan) and GtfD (soluble glucan). The effects
of propolis on Gtf from Streptococcus sanguis (soluble glucan synthesis) was also
explored. The EEP from both regions effectively inhibited the activity of all
Gtfs in solution (75-95%) and on the surface of sHA beads (45-95%) at
concentrations between 0.75 and 3.0 mg of propolis/ml. However, the two samples
of propolis showed different levels of inhibition on each of the enzymes tested.
In general, EEP RS demonstrated a significantly higher inhibitory activity on
GtfB and C activities (both solution and surface assays) than EEP MG at
concentrations between 0.047 and 0.187 mg/ml (p<0.05). EEP MG, on the other hand,
exhibited a greater inhibitory effect on the activities of surface GtfD (at
0.375, 0.75 and 1.5 mg/ml) and S. sanguis Gtf (at 1.5 and 3.0 mg/ml; p<0.05).
These data indicate that EEP is a potent inhibitor of Gtf enzymes in solution and
adsorbed on an experimental pellicle; however, its effect on Gtf activity is
variable depending on the geographical origin of the propolis samples. There is a
need to identify the active compounds of propolis.
PMID- 11014910
TI - Binding characteristics of Streptococcus mutans for calcium and casein
phosphopeptide.
AB - Casein phosphopeptides (CPP) stabilize amorphous calcium phosphate (ACP) and may
be used to localize ACP in dental plaque, maintaining a state of supersaturation
with respect to tooth enamel, reducing demineralization and enhancing
remineralization [Reynolds, J Dent Res 1997;76:1587-1595]. The aim of this paper
is to investigate these effects by measuring the affinity and capacity of
Streptococcus mutans for CPP-ACP. Using the equilibrium dialysis system described
by Rose and Hogg [Biochim Biophys Acta 1995;1245:94-98], assessment of calcium
binding by a plaque streptococcus at a fixed CPP-ACP concentration gives a series
of CPP-ACP-influenced dissociation constants for calcium. These data can then be
used to derive a true dissociation constant for CPP-ACP itself. The results
demonstrate that CPP-ACP binds with about twice the affinity of the bacterial
cells for calcium up to a value of 0. 16 g/g wet weight cells. Application of CPP
ACP to plaque may cause a transient rise in plaque fluid free calcium which may
assist remineralization. Subsequently, CPP-ACP will form a source of readily
available calcium to inhibit demineralization. Hence, CPP-ACP binds well to
plaque, providing a large calcium reservoir, which is likely to restrict mineral
loss during a cariogenic episode and provide a potential source of calcium for
subsequent remineralization. Overall, once in place, CPP-ACP will restrict the
caries process.
PMID- 11014912
TI - Immunohistochemical assessment of collagen types I, III, IV and VI in biopsy
samples of the bovine uterine wall collected during the oestrous cycle.
AB - Uterine biopsies were collected at cycle days 1 (oestrous), 8, 15 and 19 in six
cows. Unfixed cryostat sections were used to immunolocalise collagen types I,
III, IV and VI by an indirect FITC method. Collagen I was sparsely found in the
endometrium where it formed a fine meshwork of thin fibres directly below the
surface epithelium, clearly visible only at cycle days 8 and 15. Collagen III
formed the bulk of connective tissue fibres and was arranged in fine aggregates
within the superficial endometrial stroma, while in the deeper areas it consisted
of many thick fibre bundles. Collagen IV was found in basement membranes
underlying all endometrial epithelia. Furthermore, it surrounded smooth muscle
cells of blood vessels. A few single fibrils also stained positively within the
endometrial stroma, more numerous at cycle days 1 and 19 as compared to days 8
and 15. Collagen VI formed a mesh of fine and pericellularly situated fibrils
within the endometrial stroma. The contribution of the collagen types studied to
the connective tissue of caruncles, blood vessels, lymph follicles, and
myometrium is also reported. The results of the present study indicate that the
connective tissue of the bovine uterine wall is composed of different collagen
types, which exhibit a characteristic distribution pattern each. The day of cycle
may influence amounts and organisation of collagen types I and IV as demonstrated
here at the light-microscopical level.
PMID- 11014911
TI - A randomised controlled trial of the caries-preventive efficacy of a
chlorhexidine-containing varnish in high-caries-risk adolescents.
AB - A professionally applied two-stage chlorhexidine varnish, Chlorzoin((R)), was
developed to achieve sustained release and minimise the problems of staining and
bad taste associated with chlorhexidine mouthrinses. The primary aim of this
randomised controlled clinical trial was to assess the efficacy of Chlorzoin in
reducing the caries increment in high-caries-risk adolescents. Secondary aims
included investigating the effect of compliance upon caries increment, the effect
of Chlorzoin upon salivary mutans streptococci levels and assessing the benefit
of individual dental health advice by dental auxiliaries in a community setting.
1,240 children, initially aged 11-13 years, assessed to be at high caries risk
were recruited into the trial. The trial design involved four arms: an
observational group, a control group, an active (Chlorzoin) varnish group and a
placebo varnish group. All subjects were examined annually by a calibrated
examiner who was blind to the group allocation. Three-year caries increments were
calculated using clinical, clinical and fibre-optic transillumination, and
clinical and bitewing data sets. The results indicated that the use of Chlorzoin
had an initial effect on mutans streptococci levels but that no long-term
reduction in caries increment or mutans streptococci infection could be detected.
One reason for this lack of efficacy may have been the regimen of reduced
frequency of varnish applications after the initial period. Children who followed
the protocol and, therefore, were seen regularly by dental auxiliaries had a
lower caries increment than those who did not. This finding was independent of
varnish allocation. In summary, under this regimen, Chlorzoin has been found to
be effective in decreasing salivary mutans streptococci but ineffective as a
caries-preventive agent in high-risk Scottish children when applied pragmatically
in a community setting.
PMID- 11014913
TI - Investigation of the female canine urethral vascular plexus using light and
scanning electron microscopy: a contributing factor to urinary continence.
AB - The vascular system of the female canine urethra was investigated by means of
serial histological sections, vascular corrosion casts and scanning electron
microscopy. The urethral vascular plexus, located in the proprial connective
tissue between the epithelium and the smooth musculature, consisted of sinusoids.
It could be divided distally into two parts defined by a constriction in the
transitory region between the third and fourth urethral quarters. The proximal
segment of the plexus was composed of interconnected longitudinal tubes, whereas
the distal part assumed a more net-like form and was continuous with the
vestibular plexus. Small arteries usually ran alongside the sinusoidal vessels
for a considerable distance before emptying either directly or through branches
into the plexus. This vascular arrangement establishes the vascular plexus as a
structure similar to an erectile tissue with an arterial inflow, thereby
emphasizing the importance of the plexus as a major contributory component
guaranteeing urinary continence.
PMID- 11014914
TI - Quantitative three-dimensional analysis of chondrocytic kinetic responses to
short-term stapling of the rat proximal tibial growth plate.
AB - Although it has been demonstrated clinically that controlled compression across a
growth plate will slow the rate of endochondral ossification and thus can be used
to correct angular limb deformities, the cellular-based mechanism by which
altered growth is achieved is poorly understood. This study used short-term
uniaxial stapling of the rat proximal tibial growth plate as an experimental
system to study chondrocytic responses in the growth plate that account
quantitatively for the decreased rate of growth. Growth plates were labeled with
oxytetracycline to measure bone growth, and with bromodeoxyuridine to analyze
proliferative cell kinetics. Multiple indicators of chondrocytic activity,
measured by stereological parameters, were analyzed using growth rate as the
primary dependent variable. The unique feature of this analysis was the creation
of three-dimensional reconstructions that allowed analysis of data in all
directions with distance from the staple. A significant observation was that for
the entire operated limb after both 3 and 6 days, all chondrocytic kinetic
parameters were affected, indicating that proliferative and hypertrophic
responses both act to decrease growth rate in response to stapling. This
contradicted our hypothesis that proliferative and hypertrophic responses could
occur independently, and that small changes in rate would be attributed primarily
to the former and large changes to the latter. The data from this study also
demonstrate that volume regulation during hypertrophy can be affected by a
primarily mechanical perturbation. Because changes in hypertrophic cell number
and volume throughout the growth plate that occur by day 3 remain similar at day
6, the initial modulation of chondrocytic volume and shape may represent the
limit of the response while maintaining a growth plate capable of continued
growth.
PMID- 11014915
TI - The superficial anulus fibrosus ligament. An incipient description of a separate
ligament between the lumbar anterior longitudinal ligament and the intervertebral
disc.
AB - A previously unknown ligament, the superficial anulus fibrosus ligament (SAFL),
situated on the ventral part of the L5 intervertebral disc (ID) was observed and
described from autopsy material. Twenty-eight cadaveric specimens from 12 black
and 16 white persons aged 17-30 years were studied during routine forensic
autopsies. The anterior longitudinal ligament was separated from the ID and the
ventral part of the SAFL was visualized. The SAFL samples were removed, measured
and studied with both conventional histology and examination by transmission
electron microscopy. The SAFL was a completely separate ligament at the level of
the L5-S1 ID situated between the anterior longitudinal ligament and the anulus
fibrosus of the ID. The fibers of the ligament were vertically oriented. A
difference in distance between the L5-S1 vertebral bodies ventrally was noted in
the two groups studied (18.7 +/- 1.2 mm in the black vs. 15.2 +/- 1.0 mm in the
white, p < 0.001), indicating a difference in the ventral thickness of the
intervertebral disc. Also, there was a difference in the length (black: 17.7 +/-
1.6 mm vs. white: 14.1 +/- 1.1), thickness (black: 3.3 +/- 0.3 mm vs. white: 2.1
+/- 1.9), and the cross-sectional area (black: 58.2 +/- 6.7 mm(2) vs. white: 26.5
+/- 2.7 mm(2), p < 0.001) of the SAFL. Conventional light microscopy revealed no
obvious differences. However, transmission electron microscopy revealed notably
larger collagen fibril diameter in black than white subjects. In conclusion, the
interbody distances were greater in the black group, indicating a greater
intervertebral disc thickness, compared to that of the white. Furthermore, the
SAFL was significantly longer and thicker in the black than in the white group.
Albeit unsubstantiated, these race-specific macroscopic findings may have
implications for understanding the etiology of various low back stress problems.
PMID- 11014916
TI - Changes in the structure of dentine from cheek teeth of deer chronically exposed
to high levels of environmental fluoride.
AB - The purpose of this study was to examine, using backscattered electron imaging,
the changes occurring in the structure of the dentine including giant tubules in
the teeth of deer chronically exposed to fluoride. The primary and secondary
dentine was characterised by the presence of interglobular dentine and regular
bands of hypo- and hypermineralised dentine. Giant tubules in the unworn teeth of
animals exposed to low and high levels of fluoride were characterised by a large
lumen and hypermineralised rim in which there were calcospherites. With the
occlusal wear of the teeth tubules beneath the immediate surface of the exposed
dentine in teeth from fluorotic animals became occluded with mineral, but in low
fluoride animals some tubules at the surface were not occluded with mineral. It
is suggested that mineral which occludes the tubules may come from both intrinsic
and extrinsic sources. The presence of some open tubules at the immediate surface
in the worn teeth of animals exposed to low fluoride suggests an extrinsic source
for this mineral.
PMID- 11014917
TI - The dentinal structure of equine incisors: a light and scanning electron
microscopic study.
AB - This paper gives an anatomical overview of the dentinal structure in equine
incisor teeth with special reference to the three-dimensional organization, the
number and the diameter of the dentinal tubules. The spatial arrangement of
equine dentine was examined by scanning electron microscopy of occlusal surfaces
and longitudinally fractured teeth and by light microscopy of both decalcified
and ground sections. The dentinal tubules of the peripherally situated primary
dentine were directly continuous with those of the circumpulpal secondary
dentine. The tubules had numerous side branches along their entire course and
ramified into terminal branches near the dentino-enamel junction. Tubules of
tertiary dentine, situated in the centre of the dental star, were few in number
and not continuous with those of the surrounding secondary dentine. On non-etched
incisors tubular orifices were clogged by an amorphous smear layer that covered
the occlusal surface. On etched occlusal surfaces the numerical tubular density
was calculated in different zones. The largest number of tubules per unit area
was situated in the secondary dentine forming the dark periphery of the dental
star, whereas the smallest number was present in the tertiary dentine located in
the pale centre of the dental star. Dentinal tubular diameters were measured at
various distances from the pulp. They were widest near the pulpal wall and
narrowed progressively towards the dentino-enamel junction. Tubular widths
measured on etched occlusal surfaces were considerably larger than those measured
on undecalcified incisors due to the removal of intratubular dentine during the
etching process.
PMID- 11014918
TI - Delayed expression of calbindin D28k during regeneration of the periodontal
Ruffini endings of the rat incisor following injury to the inferior alveolar
nerve.
AB - Expression of calbindin D28k (CB)-like immunoreactivity (-LI) was compared with
that of protein gene product 9.5 (PGP 9.5), a general neuronal marker, in the
periodontal ligament of the rat lower incisor following resection of the inferior
alveolar nerve (IAN). In normal animals, the periodontal nerve fibers showing PGP
9.5-LI formed either Ruffini endings with expanded arborization or thin free
nerve endings in the alveolar half of the ligament. Thick CB-like immunoreactive
(-IR) nerve fibers terminated in a dendritic fashion in the same region, but thin
CB-IR nerve fibers were rarely detected. During the 3 days following resection of
the IAN, most of the PGP 9.5-IR and all CB-IR nerve fibers disappeared.
Regenerated PGP 9.5-IR nerve fibers appeared around 7 days after resection, in
contrast to the very small number of regenerated CB-IR nerve fibers. Around 21-28
days following resection, the number and terminal morphology of regenerated PGP
9.5-IR nerve fibers were comparable to those observed in normal animals, but the
number of regenerated CB-IR nerve fibers was still smaller. The terminal
morphologies of these regenerated CB-IR nerve fibers showed less expansion
compared with normal animals at these post-injured periods. The number of
regenerated CB-IR nerve fibers increased gradually to return to normal by 56 days
following injury. The delayed expression of CB in the regenerated periodontal
Ruffini endings suggests that the functional recovery of periodontal Ruffini
endings occurred after the regeneration of periodontal Ruffini endings had been
completed.
PMID- 11014919
TI - Structure of the middle ear and auditory tube in the house musk shrew, Suncus
murinus.
AB - Anatomical features of the middle ear and auditory tube (AT) in the house musk
shrew, Suncus murinus, were examined by dissection and light microscopy. The
tensor veli palatini (TVP) and tensor tympani (TT) have no connections with the
wall or cartilage of the AT although they are connected by the intermediate
tendon. None of the levator veli palatini (LVP) muscle bundles are attached to
the AT. The salpingopharyngeus (SA) alone has its origin on the caudal edge of
the tubal cartilage. The origin extends to the pharyngeal two thirds of the
cartilage. The SA originates perpendicular to the AT and runs caudomedialward.
Some SA muscle bundles intermingle with those of the palatopharyngeus to end on
the dorsal wall of the pharynx. The observations provide no evidence that the
TVP, LVP and TT have any role in AT function. The only muscle affecting the AT
function in S. murinus is the SA, and it would be the AT dilator.
PMID- 11014920
TI - Localization of P2X receptors in the guinea pig adrenal gland.
AB - The distribution of each of the seven subtypes of adenosine 5'-triphosphate (ATP)
gated P2X receptors was investigated in the adrenal gland of guinea pig utilizing
immunohistochemical techniques. The occurrence of positive immunoreactivity with
specific distribution was observed for antibodies against P2X(1), P2X(2), P2X(5)
and P2X(6) receptors, whereas no immunoreactivity was found for antibodies
against P2X(3), P2X(4) and P2X(7) receptors. Immunoreactivity for P2X(1) occurred
in cells of the inner region of the zona reticularis of the cortex, Several
P2X(2)-immunoreactive connective tissue-like elements were located between groups
of cortical cells of the zona reticularis. Bundles and terminals of nerve fibres
as well as intrinsic neurones gave positive immunoreactivity for P2X(5). The
immunoreactive nerve fibres appeared to belong to both extrinsic preganglionic
sympathetic and intrinsic immunoreactive neurones. Chromaffin cells were
immunoreactive for the P2X(6) receptor antibody. The widespread and specific
distribution of P2X receptor subtypes in the adrenal gland suggests significant
roles for purinergic signalling in the physiology of the guinea pig adrenal
gland.
PMID- 11014921
TI - Measurement of hepatic tissue hypoxia using near infrared spectroscopy:
comparison with hepatic vein oxygen partial pressure.
AB - Hepatic hypoxia occurs during liver surgery and transplantation. The critical
level associated with irreversible hepatocellular damage is unknown. Measurement
of hepatic tissue oxygenation and hepatic vein oxygen partial pressure (HVPO(2))
reflects oxygen supply and consumption. Near infrared spectroscopy (NIRS) can be
used to monitor hepatic oxyhaemoglobin (HbO(2)), deoxyhaemoglobin (Hb) and
cytochrome oxidase (Cyt Ox) oxidation. This study compared regional hepatic
tissue oxygenation (HbO(2), Hb and Cyt Ox) using NIRS with HVPO(2). The use of
tissue oxygenation measured by NIRS and HVPO(2) as indicators of hepatic tissue
hypoxia was also investigated. Large Landrace pigs (n = 5) underwent laparotomy
and liver exposure. Systemic and hepatic haemodynamics were monitored
continuously. NIRS probes were placed on the liver to record continuously HbO(2),
Hb and Cyt Ox. Graded hypoxaemia was achieved by stepwise reduction of the
fraction of inspired oxygen (FiO(2)) from 30% (baseline) to 4%. A significant
decrease in hepatic arterial blood flow and total hepatic blood flow was seen
with severe hypoxaemia while there was no significant change to portal vein blood
flow. Oxygen partial pressures in the hepatic artery, portal vein and hepatic
vein decreased progressively with all grades of hypoxaemia. There was an
immediate reduction of hepatic HbO(2) and simultaneous increase in hepatic Hb
with all grades of hypoxaemia. Hepatic Cyt Ox was reduced significantly only with
FiO(2) < or =10%. A significant correlation (p<0.001) was found between the
changes in hepatic oxygenation parameters measured by NIRS and HVPO(2). HVPO(2)
measurement did not predict the reduction in intracellular tissue oxygenation
demonstrated by NIRS with a decrease of Cyt Ox oxidation. In conclusion there was
a good correlation between the tissue oxygenation parameters measured by NIRS and
HVPO(2). However, the reduction of intracellular oxygenation found with severe
hypoxaemia was demonstrated only by NIRS.
PMID- 11014922
TI - The effects of allopurinol in hepatic ischemia and reperfusion: experimental
study in rats.
AB - BACKGROUND/AIMS: Some studies have shown that postischemic hepatic dysfunction is
mainly due to oxygen free radicals that are generated by xanthine oxidase. The
present study was undertaken to determine the effect of allopurinol, an inhibitor
of xanthine oxidase, on oxidative stress, liver injury and histologic alterations
induced by hepatic ischemia-reperfusion in rats. METHODS: One hundred and sixty
Wistar rats were used and divided into three groups. Group 1: sham operation;
group 2: 50 min of ischemia followed by 1 h of reperfusion, and group 3:
pretreatment with allopurinol and 50 min of ischemia followed by 1 h of
reperfusion. The effect of allopurinol was evaluated by plasma levels of alanine
aminotransferase and aspartate aminotransferase, histopathologic studies, and
lipid peroxidation measured by the thiobarbituric acid reactive substances method
and chemiluminescence initiated by tert-butyl hydroperoxide technique. RESULTS:
Ischemia followed by reperfusion promoted an increase in lipid peroxidation of
the hepatic cells when compared to the sham-operated group (p<0.05). This
increase was attenuated in the group treated with allopurinol (p< 0.05).
Allopurinol also showed a protective effect on hepatocellular necrosis (p<0.05),
and the plasma levels of liver enzymes returned earlier to the normal range in
rats pretreated with allopurinol in comparison to those that did not receive the
drug (p<0.05). CONCLUSIONS: Allopurinol exerted a protective effect on hepatic
ischemia and reperfusion in rats. The administration of this drug prior to liver
operations should be considered to be submitted to trials in humans.
PMID- 11014923
TI - Hepatic lymphocyte transplantation in hyperbilirubinemic gunn rats.
AB - Hepatic lymphomyeloid cells (HLCs) are thought to contain liver stem cells. We
investigated whether HLCs generated enzyme-producing cells in vivo. HLCs from
normal Wistar/Shi rats and rats in which liver ischemia was induced using a
portal clamp 4 days previously were studied histopathologically and characterized
using flow cytometry. Splenic lymphocytes obtained from these animals were
compared as a control. The proliferative activity of HLCs and splenic cells from
both groups was also tested by stimulation with concanavalin A. HLCs contained a
significantly higher number of NK-T cells and OV6+ cells compared with the
splenic cells. The HLCs from rats in which liver ischemia was induced tended to
have greater proliferative activity than those from normal rats, while the
proliferative activity of splenic lymphocytes was impaired by liver ischemia. The
HLCs obtained from Wistar/Shi rats with liver ischemia were then injected into
hereditary hyperbilirubinemic Gunn rats to determine whether the HLCs generated
enzyme-producing cells. After injection of these stimulated HLCs, the titer of
serum bilirubin in the recipient rats was markedly reduced over a long time
course (6.80+/-0.93 to 4.87+/-0.22 mg/dl after 1 month and 3.52+/-1.33 mg/dl
after 6 months). The results of the present study indicate that HLCs have
different populations than splenic cells, and ischemia-reperfusion of the liver
increased their proliferative activity. HLC transplantation successfully reduced
high bilirubin levels over a long time course.
PMID- 11014924
TI - Influence of positive end-expiratory pressure ventilation on peripheral tissue
perfusion evaluated by measurements of tissue gases and pH. An experimental study
in pigs with oleic acid lung injury. .
AB - Measurements of subcutaneous oxygen tension (PscO(2)), subcutaneous carbon
dioxide tension (PscCO(2)) and subcutaneous pH (pHsc) were used for evaluation of
peripheral oxygenation in pigs subjected to oleic acid-induced lung injury during
ventilation with increasing levels of positive end-expiratory pressure (PEEP).
Lung injury resulted in a decrease of arterial oxygen tension (PaO(2)) from 93 to
37 mm Hg (p<0.01) with maintained cardiac output. PscO(2) decreased from 45 to 17
mm Hg (p<0.01) and pHsc from 7.47 to 7.39 (p<0.05), and PscCO(2) increased from
46 to 59 mm Hg (p<0.05). Increase of PEEP level between 5 and 20 cm H(2)O
resulted in a continuous increase of PaO(2) from 45 to 145 mm Hg and a decrease
of cardiac output from 4.1 to 2.0 liters/min (p<0.01). PscO(2) increased up to a
PEEP level of 15 cm H(2)O, reaching 26 mm Hg. Further increase of PEEP level up
to 20 cm H(2)O resulted in an increase of PscCO(2) from 65 to 71 mm Hg (p<0.05)
and a decrease of pHsc from 7.31 to 7.29 (p<0.05). IN CONCLUSION: measurements of
tissue gases and pH can be used to evaluate optimum peripheral tissue oxygenation
during titration of PEEP level. Whether these measurements can be used as the
only indicator to guide therapy in an individual case remains to be studied.
PMID- 11014925
TI - Intimal hyperplasia after long-term venous catheterization.
AB - OBJECTIVE: Intimal hyperplasia is a well-known consequence of arterial injury and
arterialization in vein grafts. However, the subacute and chronic vein wall
changes which occur after catheterization have not been well studied. In this
animal study, intimal hyperplasia in the vein wall after catheterization was
examined. METHODS: A silicon catheter was placed in the anterior caval vein of 54
rats. After in situ fixation at scheduled intervals (1 day to 6 months), the
pathologic changes in the vein wall were studied on semi-serial histology
sections by means of light microscopy. RESULTS: Three forms of intimal
hyperplasia could be observed: plaque-like, papillary-like and incorporation of
the mural part of the sleeve into the underlying vein wall. Although the
appearance of each was different, their composition was identical. All were
mainly composed of alpha-actin-positive cells and collagen localized above the
internal elastin layer, and covered by endothelium if facing the lumen. The
plaque-like and papillary-like forms were mainly localized in the anterior vena
cava, while sleeve incorporation mainly occurred in the jugular vein. Plaque-like
and papillary-like intimal hyperplasia could be seen together on the same slide,
but these two forms were never seen together with sleeve incorporation.
CONCLUSION: Intimal hyperplasia occurs after venous catheterization and is
probably caused by chronic injury to the vein wall due to knocking and rubbing
movements of the catheter against the wall.
PMID- 11014926
TI - Diverting colostomy increases anastomotic leakage in the rat colon.
AB - In the present study, we examined the effect of a diverting colostomy on the
intestinal healing of colonic anastomosis in the rat. For this purpose, we
created a colonic stenosis 2 days prior to the formation of a distal one-layer
end-to-end anastomosis with or without a proximal double-barreled deviation
colostomy in the rats. Radiological examination of anastomotic leakage was
performed daily for 4 days and on day 7 after the operation. We found that
anastomotic leakage was markedly increased in rats with a diverting colostomy
compared to control animals; i.e. the leakage index (percentage of days with
leakage during the experimental period) in colostomy rats was 29%, whereas in
animals with no colostomy, the leakage index was only 7%. Interestingly, it was
observed that anastomosis formation was associated with a higher mortality rate
in rats with colostomy diversion (36%) compared to control animals (7%). However,
there was no difference in suture holding capacity on day 7. Moreover, body
weight decreased significantly in the colostomy group compared to rats without
surgical defunctioning when followed for up to 7 days after surgery. Taken
together, our novel findings suggest that a diverting colostomy may increase
intestinal leakage after anastomosis formation in the rat colon. Thus, the role
of proximal colostomy in the protection of colorectal anastomosis needs to be
reevaluated and further investigations are required to resolve the influence of
surgical defunctioning on intestinal healing.
PMID- 11014927
TI - 11th walter brendel symposiumon applied immunology and microcirculation. mauls,
Sudtirol, italy, february 7-9, 2000
PMID- 11014928
TI - Disorders of the epithelial Na(+) channel in Liddle's syndrome and autosomal
recessive pseudohypoaldosteronism type 1.
AB - The epithelial Na(+) channel (ENaC) is the key step in many Na(+)-absorptive
epithelia, such as kidney and distal colon, that controls the overall rate of
transepithelial Na(+) transport. ENaC is composed of three homologous subunits,
alpha, beta, and gamma. The alpha subunit is the key subunit for the formation of
a functional ion channel, while the beta and gamma subunits can greatly
potentiate the level of expressed Na(+) currents. ENaCs belong to the recently
identified DEG/ENaC supergene family, sharing the same basic structure with
cytoplasmic amino and carboxy termini, two transmembrane regions, and a large
extracellular loop. The human ENaC genes have been cloned, and using genetic
linkage analysis the involvement of ENaC gene mutations in two distinct human
diseases, Liddle's syndrome and autosomal recessive pseudohypoaldosteronism type
1 (PHA-1), has been demonstrated. In Liddle's syndrome, gain-of-function
mutations in the beta or gamma ENaC subunits have been found; all identified
mutations so far reside in the carboxy terminus of the protein, either deleting
or modifying the functionally important PY motif. In PHA-1, loss-of-function
mutations in the alpha, beta, or gamma subunits have been found; these mutations
either truncate a significant portion of the structure or modify an amino acid
that plays an important role in channel function. In this review, our current
understanding about ENaC and the pathophysiology of Liddle's syndrome and PHA-1
caused by ENaC mutations will be discussed.
PMID- 11014929
TI - Defective processing and trafficking of water channels in nephrogenic diabetes
insipidus.
AB - Nephrogenic diabetes insipidus (NDI) is a disease characterized by the inability
of the kidney to concentrate urine upon stimulation with vasopressin. Mutations
in the gene for aquaporin-2 (AQP2) are the cause of the autosomal recessive and
autosomal dominant forms of NDI. Mutant AQP2 proteins, found in autosomal
recessive NDI, were shown to be misfolded and retarded in the endoplasmic
reticulum. One mutant protein leading to autosomal dominant NDI, E258K, has been
analyzed in detail. It was shown that this mutant was not retarded in the
endoplasmic reticulum but mainly retained in the Golgi network. Furthermore, this
particular mutant was able to form heterotetramers with wild-type AQP2, in
contrast to mutants found in autosomal recessive NDI. The subsequent misrouting
of complexes containing wild-type and mutant AQP2 proteins explains dominant NDI.
PMID- 11014930
TI - Defects in processing and trafficking of cystic fibrosis transmembrane
conductance regulator.
AB - In most epithelial tissues Cl(-) transport relies on the cystic fibrosis
transmembrane conductance regulator (CFTR) which has dual function as a Cl(-)
channel and as a regulator of other ion channels. More than 900 different
mutations in the CFTR gene are the cause for defective transport of Cl(-) and
Na(+) and impaired secretion or absorption of electrolytes in cystic fibrosis.
However, the CFTR mutation delta F508 is the most common reason for the
frequently inherited disease among the Caucasian population. Maturation and
processing of delta F508-CFTR is defective which leads to expression of only very
little but functional CFTR in the cell membrane. Understanding the processing and
trafficking of CFTR may give a clue to the question as to how the expression and
residual function of delta F508-CFTR can be enhanced, and may lead to the
development of new pharmacological tools for the treatment of cystic fibrosis.
PMID- 11014931
TI - Mechanisms of renal calcium transport.
AB - The kidneys play a key role in the integrated regulation of calcium homeostasis.
Calcium absorption takes place throughout the nephron. Proximal tubules, thick
ascending limbs of Henle's loop, and distal tubules are the major sites of
calcium absorption. The mechanisms of absorption vary significantly from one
segment to another, as does the extent of hormonal regulation. At one extreme is
the considerable reabsorption by proximal tubules that proceeds primarily, if not
entirely, by a paracellular pathway that is not regulated by hormones or drugs.
In thick ascending limbs, calcium absorption occurs through a combination of
transcellular and paracellular routes. The active, transcellular component is
regulated by parathyroid hormone (PTH) and calcitonin, whereas the passive,
paracellular route is governed by the extent of concomitant sodium absorption. At
the other extreme is the distal tubule, where calcium absorption is entirely
transcellular and is regulated by PTH,1,25[OH(2)] vitamin D(3), calcitonin, and
by calcium-sparing drugs such as thiazide-type diuretics. The present review
focuses on recent insights into the mechanisms of transcellular calcium movement
and highlights the discovery of an epithelial calcium channel, ECaC, that may
mediate calcium entry in distal tubules.
PMID- 11014932
TI - Molecular pathology of renal chloride channels in Dent's disease and Bartter's
syndrome.
AB - Recent advances in molecular biology have characterised a new class of chloride
channels that are referred to as voltage-gated chloride channels (CLCs). To date
9 such CLCs (CLC-1 to CLC-7, CLC-Ka and CLC-Kb which are respectively encoded by
the genes CLCN1 to CLCN7, CLCNKa and CLCNKb) have been identified in mammals.
Mutations in 2 of these, referred to as CLC-5 and CLC-Kb, have been defined in
the hypercalciuric nephrolithiasis disorders of Dent's disease and a form of
Bartter's syndrome, respectively. In addition, other forms of Bartter's syndrome
have been defined with mutations involving the bumetanide-sensitive sodium
potassium-chloride co-transporter (NKCC2) and the potassium channel ROMK.
Finally, mutations of the thiazide-sensitive sodium chloride co-transporter
(NCCT) are associated with Gitelman's syndrome, in which hypocalciuria and
hypomagnesaemia are notable features. These molecular genetic studies have
increased our understanding of the renal tubular mechanisms that regulate mineral
homeostasis.
PMID- 11014933
TI - Severely impaired urine-concentrating ability in mice lacking the CLC-K1 chloride
channel.
AB - To analyze the physiological functions of CLC-K1 in vivo, we generated mice
lacking CLC-K1 by targeted gene disruption. Homozygous mutant Clcnk1-/- mice
produced approximately 5 times more urine than Clcnk1+/- and Clcnk1+/+ mice.
After 24-hour water deprivation, Clcnk1-/- mice became severely dehydrated and
lethargic. Intraperitoneal injection of the V2 agonist, deamino-Cys(1), D-Arg(8)
vasopressin, induced an increase in urine osmolarity in Clcnk1+/- and Clcnk1+/+
mice from approximately 1,000 to approximately 3,000 mosm/kg H(2)O, whereas the
increase in Clcnk1-/- mice was only from approximately 600 to approximately 840
mosm/kg H(2)O, indicating nephrogenic diabetes insipidus in Clcnk1-/- mice. These
results clearly established that CLC-K1 plays a major role in the urinary
concentrating mechanisms.
PMID- 11014935
TI - Changes in Finnish dental consonant articulation in cleft lip/palate children
between 6 and 8 years of age.
AB - The aim of this study was to clarify changes in the occurrence of
misarticulations of dental consonants /r/, /s/ and /l/ between 6 and 8 years of
age in cleft-affected Finnish children and to compare the effects of gender and
to estimate if spacing due to changing of maxillary incisors could explain
changes in articulation of these sounds. The subjects were 133 (47 girls, 86
boys) Finnish-speaking non-syndromic children with isolated cleft palate (n =
34), cleft lip/alveolus (n = 49), unilateral (n = 33), and bilateral (n = 17)
cleft lip and palate. The results showed that there were no statistically
significant differences between genders according to changes in articulation
abilities by the age of 8 years. Eighty-one percent of the subjects with
misarticulations at the age of 6 years still misarticulated at 8 years of age,
and 16% of the subjects without misarticulations at the age of 6 years
misarticulated at the age of 8 years; /s/ and /l/ misarticulations were
eliminated more often than /r/ errors. New misarticulations were diagnosed at the
age of 8 years in the same way in the groups with (14%) and without (16%)
misarticulations at the age of 6 years. Dental arch spacing due to changing of
maxillary incisors does not seem to explain new misarticulations of /r/, /s/ and
/l/ sounds estimated at the age of 8 years.
PMID- 11014934
TI - Molecular characteristics of phosphate transporters and their regulation.
AB - A key process in overall P(i)-homeostasis is renal proximal tubular reabsorption
of inorganic phosphate (P(i)), which involves secondary active sodium/phosphate
(Na(+)/P(i)) cotransport reabsorption at the brush border membrane. Among the two
different molecularly identified Na(+)/P(i) cotransporters, the type-IIa
Na(+)/P(i) cotransporter (NaPi-IIa) accounts for up to 70% of brush border
membrane transport. Regulation of renal P(i) reabsorption centers around brush
border membrane insertion and retrieval of transporter protein under the
influence of hormonal and nonhormonal factors. Immunohistochemical and
fluorescence techniques have provided new insights into the tissue distribution
and the regulation processes. The intrinsic electrogenicity of NaPi-IIa, has
allowed detailed studies of the transport kinetics of NaPi-IIa and, combined with
mutagenesis methods, structure-function information at the protein level is
emerging.
PMID- 11014936
TI - Developing a language screening test for Arabic-speaking children.
AB - This report gives an account of general and specific issues associated with
developing an Arabic-language screening test for children aged between 3 and 12
years. Challenges, dilemmas and stages in the developmental process are
discussed. The development of the Arabic Language Screening Test: Preschool and
School Age illustrates the process. Issues and stages included: (1) arriving at a
consensus about scope and purpose; (2) conceptualizing tasks and items; (3)
specifying item content and structure; (4) field-testing the screening tool in a
circumscribed environment; (5) developing a robust scoring and interpretation
system for determining Pass or Fail, and (6) establishing the degree of accuracy
in differentiating children with and without language disorders. The product is a
screening test of verbal and related nonverbal abilities with parallel components
for children of preschool (3-5 years) and elementary school age (6-12 years).
Normative data were collected for 750 Arabic-speaking children in Jordan and
Palestine, distributed fairly equally between the ages of 3 and 12 years.
Normative means increased with age and standard deviations decreased. Interscorer
agreement (99%), internal consistency (Cronbach alpha = 0.98) and diagnostic
sensitivity (over 90% accuracy) were high. Constraints and limitations in the
development of the test are described and discussed from both objective and
personal perspectives.
PMID- 11014937
TI - A method to measure speaking time and speech sound pressure level.
AB - Many voice disorders are associated with vocal loading, but easy measurement of
the vocal load has not been possible so far. To fulfil this need, an easily
accessible method was developed and tested. Speaking time and speaking sound
level can be recorded during normal work, and measurement can be made in a noisy
environment. The measurement is made with a pair of modern noise exposure
analysers from which the data is transferred to a personal computer, and the
voice speaking time and the related sound pressure levels are calculated with a
spreadsheet program. Suitable meters are available from various manufacturers.
The method may be applied to measure the need of voice use in different
professions, assessing a person's performance in his or her work or evaluating
the effects of voice therapy on speaking performance.
PMID- 11014938
TI - Treatment of reflux-related and non-reflux-related dysphonia with profound
gastric acid inhibition.
AB - Thirty-eight patients with dysphonia exceeding 3 months, not caused by trauma,
infection, paralysis or allergy, were studied. In all patients a 24-hour
ambulatory dual-probe pH monitoring, 5 and 20 cm above the lower oesophageal
sphincter was performed. Subsequently they were treated with lansoprazole 30 mg
once daily during 6 weeks. A voice range profile, perceptual evaluation of the
voice and videolaryngostroboscopy were performed in all patients before and after
treatment. A questionnaire about laryngeal symptoms and heartburn was completed
on the same two occasions. Thirty-nine percent (15 out of 38) of the patients had
an abnormal pH profile and were considered to have reflux-related dysphonia. Only
these patients showed a significant improvement in their subjective score on
dysphonia (p < 0.05), chronic cough (p < 0.05), dysphagia (p < 0. 05) and
heartburn (p < 0.01). Also posterior erythema decreased significantly in these
patients (p < 0.01). Only 2 of the 15 subjects did not complain of heartburn.
PMID- 11014943
TI - Changes in plasma adenosine concentrations during normal pregnancy.
AB - The aim of this study was to measure changes in plasma adenosine concentration
[ADO] during a normal pregnancy and to evaluate the possible role of platelets
and red blood cells (RBC) as causes of changes in plasma [ADO]. We measured the
plasma [ADO] in normal pregnant women (n = 11) during the first, second and third
trimesters. The mean plasma [ADO] in the third trimester was 0.41 +/- 0.08 microM
(means +/- SEM), significantly higher than in the first and second trimesters (p
< 0.05). In pregnant women, platelet and RBC counts, hematocrit and hemoglobin
concentration decreased slightly throughout the pregnancy. The elevation in the
plasma [ADO] correlated inversely with the platelet count (r = -0.43, p < 0.05).
These results suggest that an increase in the plasma [ADO] in the third trimester
may be attributed to the enhanced adenosine release from activated platelets.
PMID- 11014944
TI - Nausea and vomiting in pregnancy: an association between symptoms and maternal
prostaglandin E2.
AB - This study investigated the aetiology of nausea and vomiting in pregnancy (NVP)
in primary care using a new methodology. Eighteen women in early pregnancy had 2
blood samples taken in one 24-hour time period, one when they were symptomatic,
and another when they were symptom-free. Maternal serum levels of the candidate
agents PGE2, IL-1beta, and TNFalpha were measured. The study shows a positive
relationship between NVP and maternal serum PGE2 levels in early pregnancy.
PMID- 11014945
TI - Gamma-delta T cells in midgestation human placental villi.
AB - One question that remains is how the immune system at the maternal-fetal
interface supports tolerance of the fetus while at the same time protecting it
from infection. A potential answer is that local innate immunity is augmented
while adaptive immunity is downregulated. In this study, we focus on T cells of
the gamma-delta lineage, thought to be important in certain innate responses.
Using tissue from normal pregnancies, we documented the presence of gamma-delta T
cells and their counterpart, alpha-beta T cells, in midgestation human placental
villi. The variable presence of these two T cell lineages in this anatomic site
may suggest differential regulation, and herein we describe potential mechanisms
for this phenomenon.
PMID- 11014946
TI - Use of prostaglandin E2 for cervical ripening in pregnancies with
oligohydramnios.
AB - The effectiveness of intracervical prostaglandin E2 (PGE2) was studied in 96
primigravidas with unfavorable cervix and need for induction of labor. Group A
consisted of 49 oligohydramnios and group B of 47 cases with normal amniotic
fluid volume (controls). A single dose of 0.5 mg PGE2 gel was applied
intracervically and several parameters were recorded during the next hours. The
mean number of uterine contractions increased during the first 2 h in both
groups, decreased during the next one and did not change significantly
afterwards. The mean fetal heart rate (FHR) in group A decreased during the first
2 h and then increased, staying always within normal limits. The mean FHR in
group B increased for 2 h, decreased during the next hour and did not change
significantly afterwards. No significant differences were found between the two
groups regarding mode of delivery, Apgar score and neonatal acidosis.
Intracervical PGE2 appeared to effectively stimulate cervical ripening and labor
induction in oligohydramnios, without causing side effects to the uterus and
fetus.
PMID- 11014947
TI - Perinatal outcome in 41 sets of triplets.
AB - OBJECTIVE: To determine the perinatal outcome associated with triplet pregnancies
and to compare abdominal delivery with vaginal delivery. METHODS: Retrospective
analysis of maternal and neonatal medical records of 41 triplets. 21 were
delivered vaginally and 20 were delivered by cesarean section. MAIN OUTCOME: To
measure perinatal mortality and early neonatal complications. RESULTS: Between
January 1, 1994, and June 30, 1999, there were 41 triplets delivered at our
institution. Of these 21 triplets were delivered vaginally and 20 triplets were
delivered abdominally. The perinatal mortality rate was 32/123 (26.0%), primarily
due to the respiratory distress syndrome. The perinatal deaths are mainly at a
birth weight of 500-1,500 g (29/32; 90.6%). Breech presentation was associated
with a significantly higher perinatal mortality rate than vertex presentation
(62.5 vs. 37.5%). Cesarean delivery was associated with a higher perinatal
mortality rate than vaginal delivery (30.0 vs. 22. 2%). CONCLUSIONS: Abdominal
delivery in triplets is not superior to vaginal delivery in terms of fetal and
early neonatal outcome. The perinatal deaths are increased with low birth weight
(500-1,500 g) and with breech presentation. The main cause of neonatal mortality
is the respiratory distress syndrome.
PMID- 11014948
TI - A case of XY pure gonadal dysgenesis with 46,XYp-/47,XXYp- karyotype whose
gonadoblastoma was removed laparoscopically.
AB - A case of pure gonadal dysgenesis was investigated. The patient was an 18-year
old Japanese woman with a history of primary amenorrhea. She had poorly developed
breasts, a hypoplastic uterus, a normal vagina and infantile genitalia. The
patient's karyotype was 46,XYp-/ 47,XXYp-. Microsatellite analysis revealed that
the X chromosomes of this patient originated from one of the two maternal X
chromosomes. DNA analysis of the Y chromosome revealed that she had a deletion of
SRY (the sex-determining region on the Y chromosome). She underwent laparoscopic
gonadectomies with a final pathology consistent with gonadoblastoma. Laparoscopic
surgery is recommended as it is much less invasive and associated with rapid
postoperative recovery.
PMID- 11014949
TI - Effects of a vasopressin antagonist in women with dysmenorrhea.
AB - We compared menstrual pain, uterine contractility and blood circulation, and
plasma concentrations of vasopressin and prostaglandin F(2alpha) metabolite in
women with versus without primary dysmenorrhea, and determined the effects of a
vasopressin antagonist, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin (Atosiban),
on these parameters. Our results do not support the contention that vasopressin
is involved in the etiology of dysmenorrhea, plasma concentrations of vasopressin
being similar in dysmenorrheic women and controls, and the vasopressin antagonist
Atosiban having no effect on menstrual pain, intrauterine pressure or uterine
artery pulsatility index in dysmenorrheic women.
PMID- 11014950
TI - A clinicohysteroscopic scoring system of intrauterine adhesions.
AB - We propose a new scoring system for intrauterine adhesions (IUA) that may predict
the prognosis after hysteroscopic adhesiolysis. We analyzed hysteroscopic
findings and clinical data of patients diagnosed as having IUA by reviewing
previously published hysteroscopic classifications of IUA. The data were
subjected to evaluation according to the most popular classifications in addition
to the proposed classification using a scoring system for different parameters.
The results obtained by the proposed scoring system matched well with other
classifications regarding grade I and III IUA. But in the cases with moderate IUA
(grade II), there was overlap between the classifications (sensitivity 58.3%)
which can be attributed to considering the menstrual and reproductive history.
Further studies are needed to assess its prognostic value.
PMID- 11014951
TI - Use of intramuscular progesterone versus intravenous albumin for the prevention
of ovarian hyperstimulation syndrome.
AB - This study was designed to compare the effectiveness of intramuscular
progesterone with that of intravenous albumin in the prevention of ovarian
hyperstimulation syndrome (OHSS). Ninety-six patients at high risk to develop
OHSS (estradiol concentration >9, 000 pmol/l on the day of hCG administration and
over 20 follicles of a diameter larger than 14 mm observed by transvaginal
ultrasonography) and undergoing in vitro fertilization-embryo transfer were
enrolled. They were randomly treated with intramuscular progesterone (200 mg/day)
or 100 ml of 20% intravenous albumin in order to estimate the difference in the
incidence of OHSS. A significant difference in the incidence of moderate OHSS and
no cases of severe OHSS were observed between the groups. Our data show the
effectiveness in preventing OHSS with high doses of progesterone.
PMID- 11014952
TI - Coasting may reduce the severity of the ovarian hyperstimulation syndrome in
patients with polycystic ovary syndrome.
AB - The aim of our study was to determine the efficacy of postponing administration
of human chorionic gonadotropin while continuing daily gonadotropin-releasing
hormone agonist therapy ('coasting') to prevent the occurrence of severe ovarian
hyperstimulation syndrome (OHSS) for patients with polycystic ovary (PCO)
syndrome. Five patients with PCO who had been hospitalized due to severe OHSS in
previous in vitro fertilization and embryo transfer or intrauterine insemination
cycles at the Tottori University Hospital were included in the study. The rates
of mature oocytes and fertilization were comparable between the cycles. A
singleton pregnancy was achieved in a patient during the coasting cycle, and none
of the women developed severe OHSS in coasting cycles. The results suggest that
coasting may be an alternative method for reducing the severity of OHSS in
patients with PCO.
PMID- 11014953
TI - Effects of hormone replacement therapy on selected indices of immune function in
postmenopausal women.
AB - The purpose of this study was to examine the effects of long-term hormone
replacement therapy (HRT) on selected indices of resting immune function in
postmenopausal women. Postmenopausal women aged 54-66 were divided into two
groups, those taking HRT (n = 17) and controls (n = 19). Blood samples were
obtained and analyzed for mononuclear cell numbers, lymphocyte proliferation (LP)
and natural cell-mediated cytotoxicity (NCMC). There were no significant
differences between groups for mononuclear cell numbers. LP was significantly
higher for HRT, while NCMC was significantly lower for HRT. HRT is currently
being prescribed to postmenopausal women for prevention of a variety of medical
conditions including osteoporosis, cardiovascular disease, stroke, and
Alzheimer's disease yet HRT is often associated with altered immune parameters.
In this study, women taking HRT had increased lymphocyte blastogenesis and
decreased NCMC compared to controls.
PMID- 11014954
TI - Pure versus complicated vulvar vestibulitis: a randomized trial of fluconazole
treatment.
AB - OBJECTIVE: To examine the effectiveness of a 6-month treatment consisting of a
weekly oral dose of 150 mg fluconazole for women with vestibulitis, and to
explore the causes of treatment failure. METHODS: Forty women with vestibulitis
were randomized to either of two treatment groups. One group received a 6-month
low oxalate diet with calcium citrate complement, as a placebo, and the second
group the same diet and calcium citrate with the addition of a weekly oral tablet
of 150 mg fluconazole. The women were examined 3 months after completing
treatment, for response to therapy. RESULTS: The addition of intensive 6-month
fluconazole treatment did not lead to an outcome better than that attained by
maintaining a low oxalate diet with calcium citrate supplementation. The
satisfactory response rate was 15 and 30%, respectively. The presence of
'complicated vestibulitis', candidiasis concomitant with vestibulitis, decreases
the satisfactory response rate regardless of the type of treatment administered
(odds ratio 19.9, 95% CI 1.6, 250). CONCLUSION: Prolonged oral fluconazole is an
ineffective treatment of vestibulitis, whether pure or complicated by concomitant
vulvovaginal candidiasis. The coexistence of candidiasis and vestibulitis -
complicated vestibulitis - might represent a subset of vestibulitis that is
resistant to the currently available medical therapy.
PMID- 11014955
TI - Expression of constitutively active c-MET receptor in human choriocarcinoma.
AB - OBJECTIVE: The c-MET oncogene encodes the transmembrane tyrosine kinase receptor
for hepatocyte growth factor (HGF). Recently, either HGF or c-MET has been
knocked out in the mouse, and the mutation is associated with defects in the
development of the placenta by means of the reduction of trophoblast cells. We
examined the role of c-MET in malignant transformation of trophoblast cells.
METHODS: In four human choriocarcinoma cell lines, GCH-1, GCH-1m, NUC-1 and SCH,
the expression of HGF and c-MET was analyzed by RT-PCR and Western blotting using
anti-c-MET antibody and antiphosphotyrosine antibody. RESULTS: RT-PCR analysis
showed that no cell lines expressed HGF, however all the cell lines revealed the
expression of c-MET mRNA. c-MET receptor was expressed and also tyrosine
phosphorylated constitutively in these cell lines by Western blotting.
CONCLUSION: These results suggest that c-MET may be involved in the growth and
behavior of human choriocarcinoma although an autocrine fashion of HGF is
unlikely.
PMID- 11014956
TI - Primary peritoneal carcinoma: a report of twelve cases and a review of the
literature.
AB - Primary peritoneal carcinoma (PPC) is rare tumor histologically identical to
epithelial ovarian carcinoma (EOC); it is differentiated from EOC based on the
extent of gross ovarian involvement and microscopic invasion of the cortex. We
report 12 cases of PPC which were diagnosed in our Department during a 9-year
period. Total abdominal hysterectomy, bilateral salpingo-oophorectomy and
omentectomy were performed in 9 patients, while 3 underwent only explorative
laparotomy with bilateral salpingo-oophorectomy. All patients were treated with
postoperative platinum-based chemotherapy. After a median follow-up of 42 months,
only 5 patients are alive without disease. PPC is a rare tumor currently managed
in the same way as ovarian cancer. Primary debulking surgery and chemotherapy
represent the cornerstones of treatment. Considering the limited number of
patients with PPC, no definitive conclusion can be drawn concerning the
prognostic factors for survival.
PMID- 11014957
TI - Analysis of TH1 and TH2 cells by intracellular cytokine detection with flow
cytometry in patients with ovarian cancer.
AB - OBJECTIVE: Our aim is to assess the immune status of patients with ovarian cancer
by analyzing the ratio of T helper type 1 (TH1) to T helper type 2 (TH2)
populations in peripheral blood lymphocytes (PBL). METHODS: We examined TH1/TH2
ratios in PBL obtained from 21 ovarian cancer patients who had just received
postoperative chemotherapy, by detecting the intracellular IFN-gamma and IL-4
production with 3-color flow cytometry. Additionally, we evaluated the influence
of a granulocyte-colony stimulating factor (G-CSF) injection on TH1 and TH2
populations for a rescue of granulocytopenia due to the chemotherapy. RESULTS: We
could not find any significant difference of the TH1/TH2 ratios in terms of age,
International Federation of Gynecology and Obstetrics (FIGO) clinical stage and
clinical tumor status. As for the clinical tumor status, however, the patients
with residual cancer had a higher TH1/TH2 ratio, though it was not statistically
significant (p = 0. 15). Anticancer chemotherapy is also considered to lead to
the immunosuppressive state of the patients. TH1 and TH2 populations of PBL in
the patients during chemotherapy showed an unfavorable imbalance that was shifted
from TH1 to TH2 10 days after anticancer drug administration (p = 0.049). G-CSF
administration, on the other hand, was likely to induce a cell population shift
from TH2 to TH1 assessed by the intracellular cytokine assay (p = 0.051), and
never induced an unfavorable imbalance from TH1 to TH2 in the T cell population
by a 1-day injection of G-CSF. CONCLUSION: Together, these data indicate that the
TH1/TH2 ratio analyzed by intracellular cytokine flow cytometry seems to be a
good indicator to assess the immune status in cancer.
PMID- 11014958
TI - Uterine rupture associated with vaginal birth after cesarean section: a
complication of intravaginal misoprostol?
AB - Intravaginal misoprostol has become increasingly employed for labor induction
among patients with an unfavorable Bishop's score. Almost all of the reported
studies have specifically excluded patients with prior uterine surgery. There has
been, therefore, very little information concerning its usage among patients
attempting vaginal birth after cesarean section. We report a patient with two
prior low transverse uterine incisions who experienced uterine rupture after
having received a single 25-microg intravaginal dose of misoprostol.
PMID- 11014959
TI - Human papillomavirus genotypes in cervical cancer with different histological
features.
AB - We report the case of a 32-year-old woman having developed two cervical cancers
synchronously, an adenocarcinoma and a squamous cell carcinoma. Polymerase chain
reaction with the general primers GP5/GP6 and a subsequent enzyme-linked
immunosorbent assay to detect human papillomaviruses (HPV) resulted in isolation
of HPV 33 in the squamous cell carcinoma and HPV 18 in the adenocarcinoma. This
is the first reported case of two histologically different synchronous cervical
cancers with this distinct HPV expression pattern, and further confirms the
association of certain 'high-risk' HPV genotypes to different histological
features of carcinoma. Furthermore, the important role of microdissection for
gaining tumor tissue of different areas in molecular diagnostics is supported.
PMID- 11014960
TI - Paroxysmal nocturnal hemoglobinuria and the risk of venous thrombosis: review and
recommendations for management of the pregnant and nonpregnant patient.
AB - BACKGROUND: Paroxysmal nocturnal hemoglobinuria is a rare, clonal primitive
hematopoietic cell disorder, often affecting middle-aged adults, including women
of reproductive age. Major morbidity and mortality with this disease are often
ascribed to the development of venous thromboembolism. We reviewed the current
literature on the risk of venous thrombosis among nonpregnant and pregnant
patients, and generated recommendations for the prevention of venous
thromboembolism, as well as duration of treatment for affected patients who
develop thrombotic disease. METHODS: We searched Medline for papers published
between January 1966 and April 1999. We also requested relevant unpublished data
from speakers who attended a recent international workshop of paroxysmal
nocturnal hemoglobinuria. References from all primary data and review
publications were also examined. Only English language publications were
included. Event rates for venous thromboembolism and death were pooled using a
random effect technique. Reports of paroxysmal nocturnal hemoglobinuria during
pregnancy were summarized using descriptive statistics only. RESULTS: Thirteen
retrospective studies of paroxysmal nocturnal hemoglobinuria in nonpregnant
individuals were found. The rates of venous thrombosis varied considerably, but
were reported to affect 14.4% of all individuals [95% confidence interval (CI)
7.6-25.5]. Among patients from western nations, venous thromboembolism seemed to
develop at a higher rate (30.3%, 95% CI 26. 1-34.9). The majority of venous
thromboembolic events were intra-abdominal, principally within the hepatic and
mesenteric veins. The likely cause of death among patients with paroxysmal
nocturnal hemoglobinuria was described in nine studies: 22.2% of fatalities were
due to venous thrombosis (95% CI 11.8-38.0), more commonly in western countries
(event rate 37.2%, 95% CI 21.6-56.0). Another 20 published reports described the
outcome of 33 pregnant women with paroxysmal nocturnal hemoglobinuria. Two women
developed venous thromboembolism during pregnancy and another 2 during the
postpartum state for a combined event rate of 12.1% (95% CI 3.4-25.2), three of
which resulted in death. The all-cause mortality rate was 20.8% (95% CI 7.3
39.0). Both anemia (event rate 72.7%, 95% CI 56.5-86.3), and thrombocytopenia
(event rate 27.3%, 95% CI 13.7-43.5) were common, often necessitating red cell or
platelet transfusions. Almost half of all infants (54.8%, 95% CI 36.1-72.7) were
delivered preterm, and had a mean live birth weight of 2,800 g. Three of 34
reported births ended in death (perinatal mortality rate 8.8%, 95% C 1.9-23.7).
CONCLUSION: In accordance with the apparently high rate of venous thrombosis
among pregnant and nonpregnant individuals with paroxysmal nocturnal
hemoglobinuria, especially for fatal thrombosis, we developed practical
recommendations for the prevention and treatment of venous thromboembolic disease
in these groups.
PMID- 11014961
TI - Factor V (His 1299 Arg) in young Turkish patients with cerebral infarct.
AB - Inherited gene defects related to the coagulation system have been reported as
risk factors for stroke. Recently, a genetic component in the factor V (FV) gene
that contributes to activated protein C resistance both in the presence and
absence of FV 1691 G-->A was reported. This highly conserved FV gene haplotype
was marked as R2 polymorphism, an A to G alteration at position 4070 in exon 13
that predicts the His 1299 Arg substitutions. The aim of this study was to
evaluate the role of this mutation in Turkish children with ischemic infarct. The
case-control study included 48 patients with cerebral infarction; all were 18
years of age or younger (range: 10 months to 18 years). Ten (20.8%) of the 48
patients were found to carry the FV 1299 His-->Arg mutation, one being
homozygous. One patient who had a combination of FV 1691 G-->A and protein C
deficiency also carried the FV 4070A mutation. A homozygous FV 1299A patient had
a prothrombin (PT) 20210A mutation in the heterozygous state. The cerebral
infarct risk for FV 1299 was found to be 2.4 (95% confidence interval 0.9-6.8)
for all groups. When underlying conditions were excluded, the incidence of FV
1299 was found to be 8/35 (22.8%), but the risk was almost the same. When two
other common thrombophilic mutations (i.e. FV 1691 G-->A and PT 20210 G-->A) were
excluded, the incidence of FV 4070 mutation increased to 7/21 (33.3%). The risk
also increased to 3.9 (95% confidence interval 1.2-12.3).
PMID- 11014962
TI - Influence of fibrinogen degradation products on thrombin time, activated partial
thromboplastin time and prothrombin time of canine plasma.
AB - To investigate how thrombin time, activated partial thromboplastin time (APTT)
and prothrombin time are influenced by fibrinogen degradation products (FDP),
different concentrations (0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8 and 1.0 mg/ml) of the
purified FDP X, Y, D and E were added to the plasma of healthy dogs. If fragment
Y was added to the plasma a considerable inhibitory effect could be demonstrated
for all three test systems. A significant prolongation (p < 0.05) was found for
concentrations of > or =0.1 mg/ml (thrombin time, APTT) and > or =0.2 mg/ml
(prothrombin time). With FDP Y concentrations from >0.185 mg/ml (prothrombin
time) to >0.24 mg/ml (APTT) coagulation time was prolonged beyond the respective
reference range. As regards the other fragments, a comparable inhibitory effect
could only be shown for fragment X added to the thrombin time test system. This
effect can most probably be explained by the competition of the FDP X and
fibrinogen for the fibrinogen binding sites of thrombin, rather than by a fibrin
polymerization disorder. The results demonstrate that for plasma with normal
fibrinogen concentration the group tests are only prolonged beyond the reference
range at FDP concentrations very rarely found in spontaneous hyperfibrinolysis.
PMID- 11014963
TI - Comparison of different methods to measure fibrinogen concentration in canine
plasma with respect to their sensitivity towards the fibrinogen degradation
products X, Y and D.
AB - In this study, fibrinogen measurements according to the Clauss method,
photometric method and Jacobsson method have been investigated to find out how
they are influenced by adding in vitro the purified canine fibrinogen degradation
products (FDP) X, Y and D. Test results according to the Clauss method were found
to be underestimated if the fragments X, Y and D were added while measurements
according to the Jacobsson method turned out to underestimate the real fibrinogen
concentration if the FDP Y and D were added. The Clauss method was particularly
sensitive towards FDP. Results were considerably underestimated even with a
quantity as little as 0.05 g FDP Y or FDP D/g fibrinogen (p < 0.05). The
photometric method was only affected by FDP X leading to false high results. If
FDP X was added, fibrinogen values were also overestimated with the Jacobsson
method. Our results demonstrate that the photometric method is the most accurate.
PMID- 11014965
TI - Endothelial function, variables of fibrinolysis and coagulation in smokers and
healthy controls.
AB - OBJECTIVE: To asses endothelial function and variables of fibrinolysis and
coagulation in smokers compared to healthy controls. METHODS: Flow-associated
dilation as a marker for peripheral endothelial function and intima media
thickness as a marker for early morphologic vascular changes were measured in
otherwise healthy smokers (n = 30, 16 males and 14 females, age: 40.6 +/- 11.3
years, body mass index 24.9 +/- 3.7 kg/m(2)) and non-smoking controls matched for
age and sex using high-resolution ultrasound. Variables of the coagulation system
(thrombin-antithrombin III complex, fibrinogen) and fibrinolysis (tissue
plasminogen activator, plasmin-alpha(2)-antiplasmin complex) were determined by
ELISA and plasminogen activator inhibitor activity by means of a chromogenic
substrate test. RESULTS: Compared to the non-smoking controls, flow-associated
vasodilatation was significantly reduced (6.9 +/- 4. 4 vs. 10.5 +/- 6.2%, p =
0.01) and intima media thickness tended to be increased (0.58 +/- 0.12 vs. 0.52
+/- 0.14 mm, p = 0.08) in smokers. The thrombin-antithrombin III complex,
fibrinogen, plasmin-alpha(2)-antiplasmin complex, tissue-plasminogen activator
and plasminogen activator inhibitor activity did not differ between smokers and
controls. CONCLUSION: Our data indicate that peripheral endothelial dysfunction
is common in smokers even without major alterations in molecular markers of the
coagulation and fibrinolysis system.
PMID- 11014964
TI - Characterization of murine anti-glycoprotein Ib monoclonal antibodies that
differentiate between shear-induced and ristocetin/botrocetin-induced
glycoprotein Ib-von Willebrand factor interaction.
AB - Platelet adhesion to vascular subendothelium under conditions of high shear
stress is mediated by the platelet glycoprotein (GP) Ib-von Willebrand Factor
(vWF) interaction. The aim of this study was to characterize the murine
monoclonal antibodies (MoAbs) 27A10 and 28E6, both raised against purified GPIb.
The MoAb 27A10 is a potent inhibitor of shear-induced platelet adhesion to
collagen type I in a flow chamber at shear rates of 1,300 and 2,700 s(-1). 20
microg/ml of MoAb 27A10, furthermore, could completely block shear-induced
aggregation in a modified Couette viscometer at shear rates of 1,000 and 4,000 s(
1). On the other hand, MoAb 27A10 had a negligible effect on botrocetin-induced
GPIb-vWF binding and is only a poor inhibitor of the ristocetin-dependent
interaction. In contrast, MoAb 28E6 did abolish both the ristocetin- and
botrocetin-induced GPIb-vWF binding, whereas it did not block the shear-induced
interaction. Thus, we identify here two anti-GPIb MoAbs 27A10 and 28E6 that
either preferentially inhibit the shear-induced or the ristocetin/botrocetin
induced platelet-vWF interaction. With these tools it should be possible to more
clearly define the mechanisms by which platelets bind to vWF in vivo.
PMID- 11014966
TI - Antinuclear antibody- and extractable nuclear antigen-related diseases.
AB - In 1948, the observation of the LE cell phenomenon in a patient with systemic
lupus erythematosus (SLE) began the discovery of a broad variety of
autoantibodies directed to nuclear antigens called antinuclear antibodies (ANA).
Nowadays, different ANA serve as important diagnostic parameters for
differentiating most of the connective tissue diseases, such as SLE, neonatal
lupus syndromes, Sjogren's syndrome, scleroderma, autoimmune myositis, mixed
connective tissue disease and other overlaps. This overview summarizes the
history of ANA and their detection methods, in part to introduce the subsequent
papers dealing with special topics of ANA-related diseases in this issue.
Furthermore, the pathogenic role of these autoantibodies in targeting non-organ
specific intracellular antigens as a functional important constituent of a
subcellular particle or multimolecular complex is addressed. Notably, some of
these autoantibodies have functioned as significant tools for cell biologists to
elucidate the subcellular structures and functions of these autoantigens. In the
future, we can expect further advances to answer such important questions as why
these antigens are targets of autoantibodies, what is their pathogenic impact and
what are the triggers of autoimmunity?
PMID- 11014967
TI - The idiotypic network in antinuclear-antibody-associated diseases.
AB - Antinuclear antibodies (ANA) entail a large group of autoantibodies (Abs) that
bind certain nuclear antigens. The ANA test is a useful screening test for many
autoimmune diseases and the presence of a specific binding pattern directs
secondary testing for specific Abs associated with the suspected disease.
Idiotypes (Ids) are the antigenic constitution of the variable region of an Ab,
and they are recognized by anti-Ids Abs. The Id network is composed of
interacting Abs in which the Id determinants of each Ab are complemented by those
of another. It has a role in both physiologic and pathologic conditions. In this
communication, we review the induction of autoimmune diseases via Id
manipulation, the Ids of some ANA-associated Abs (DNA, SS-A, SS- B, Sm Abs), the
pathogenic role of Abs carrying Ids, and the clinical implications of the Id
network in autoimmunity.
PMID- 11014968
TI - Antinuclear autoantibodies: fluorescent highlights on structure and function in
the nucleus.
AB - The eukaryotic nucleus is dynamically organized with respect to particular
activities, such as RNA transcription, RNA processing or DNA replication. The
spatial separation of metabolic activities is best reflected by the
identification of functionally related proteins, in particular substructures of
the nucleus. In a variety of human diseases, the integrity of such structures can
be compromised, thus underlining the importance of a proper nuclear architecture
for cell viability. Besides their clinical relevance, antinuclear autoantibodies
(ANAs) have contributed to a large extent to the identification of subnuclear
compartments, the isolation and cloning of their components (the autoantigens),
as well a the characterization of their function. Although sophisticated
techniques, such as confocal laser scanning microscopy (CLSM), fluorescence
resonance energy transfer (FRET) and in vivo observation of cellular events have
recently been established as valuable tools to study subnuclear architecture and
function, cell biologists will continue to appreciate the specificity and power
of ANAs for their research.
PMID- 11014969
TI - Etiopathogenesis of systemic lupus erythematosus.
AB - Systemic lupus erythematosus is an autoimmune disease of unknown etiology.
Research efforts of the last few years have mainly focused on basic molecular and
cellular pathogenetic processes of the disease. Consequently, this paper reviews
the etiopathogenetic hallmarks, such as impaired amount and presentation of
nuclear antigens, production of antinuclear antibodies by T-cell-dependent B cell
stimulation and organ damage by anti-dsDNA antibodies or immune complexes that
are discussed at the present time. In summary, the hypothesis of a dysregulation
of apoptotic cell clearance is strongly supported and broadly discussed.
PMID- 11014970
TI - Use of immunoglobulin variable-region genes by normal subjects and patients with
systemic lupus erythematosus.
AB - Antibodies to specific autoantigens are serological hallmarks of systemic
autoimmune diseases. These autoantibodies are thought to represent a consequence
of immune dysregulation in these conditions, and, in part, have been shown to be
involved in their pathologic consequences. However, the mechanisms that lead to
the production of autoantibodies are still unknown. The observation that certain
autoantibodies are frequently encoded by a limited number of immunoglobulin (Ig)
variable-region gene segments suggested that a bias in the development of the Ig
repertoire might play a role in the tendency to develop autoimmunity. Whether the
use of these individual gene segments is random or different in normal subjects
and patients with systemic autoimmune disorders remains a matter of controversy.
New approaches for the analysis of variable-region genes from unstimulated
individual human B cells employing the single-cell polymerase chain reaction have
provided new insights in the B cell repertoire of both normal subjects and
patients with systemic autoimmune diseases. Using this approach, the analysis of
nonproductive and productive Ig variable-region gene rearrangements made it
possible to distinguish molecular processes, as manifested in the nonproductive
repertoire, from subsequent selection influences. An initial study in a patient
with systemic lupus erythematosus has led to the hypothesis that the molecular
generation of the B cell repertoire is similar in patients and normal subjects
but subsequent influences and, most notably, extensive mutations and receptor
editing differ significantly in shaping the peripheral IgV gene use by persons
with autoimmune diseases.
PMID- 11014971
TI - Sjogren's syndrome: autoantibodies to cellular antigens. Clinical and molecular
aspects.
AB - Autoantibodies to cellular autoantigens are usually found in sera of patients
with systemic autoimmune rheumatic diseases. Patients with Sjogren's syndrome
(SS) frequently present autoantibodies to both organ and non-organ-specific
autoantigens. The most commonly detected autoantibodies are those directed
against the ribonucleoproteins Ro/SSA and La/SSB. The presence of the antibodies
in SS is associated with early disease onset, longer disease duration, parotid
gland enlargement, higher frequency of extraglandular manifestations and more
intense lymphocytic infiltration of the minor salivary glands. Over the past
several years, the structure and function of these autoantigens have been
extensively studied. Several centers, using different techniques, have
investigated the B cell epitopes on the protein components Ro 60 kD, Ro 52kD, and
La 48 kD. Finally, increased evidence of direct involvement of anti-Ro/SSA and
anti-La/SSB autoantibodies in the pathogenesis of tissue injury has been
contributed by several studies.
PMID- 11014972
TI - Significance of autoantibodies in neonatal lupus erythematosus.
AB - Autoantibodies produced by the mother and transported into the fetal circulation
are of significant importance in the diagnosis of neonatal lupus syndromes. These
humoral autoimmune findings provide an unique opportunity to assess the
pathogenic role of autoantibodies against the Ro(SS-A)/La(SS-B) complex, most
notably for congenital heart block. Current knowledge about the involved
autoantibody-autoantigen systems, including recent therapeutic concepts of these
autoimmune syndromes, is summarized.
PMID- 11014973
TI - Antiphospholipid syndrome.
AB - Antiphospholipid syndrome (APS) is a disease characterized by venous and arterial
thromboses or spontaneous abortions and the repeated detection of
antiphospholipid antibodies (aPL). APS may be associated with another autoimmune
disease (secondary APS), particularly systemic lupus erythematosus (SLE), or
unrelated to an underlying disease (primary APS). APS affects almost all organs.
In addition to the clinical criteria, lupus anticoagulant testing and
immunological aPL determinations are required to establish the diagnosis of APS.
PMID- 11014974
TI - Diagnostic and prognostic relevance of autoantibodies in uranium miners.
AB - Uranium miners exposed to silica dust have a higher risk of developing systemic
sclerosis (SSc) and systemic lupus erythematosus (SLE). Sera of 1976 former
uranium miners were analysed for autoantibodies typical of connective tissue
disease. The frequency of some of these antibodies (anti-centromere,
topoisomerase I, -nucleolar, -dsDNA, -Ro/SSA, -La-SSB and U1-RNP antibodies) was
significantly higher compared to a gender- and age-matched control group and was
associated with the intensity of exposure as well as with clinical symptoms of
SSc or SLE. It was also shown that SSc-associated autoantibodies may serve as an
early indicator of disease development. Some differences in the autoantibody
production between silica-dust-associated and idiopathic SLE/SSc were observed
that might be caused by environmental factors in the population of uranium
miners.
PMID- 11014975
TI - Diagnostic importance of anti-proteasome antibodies.
AB - 20S proteasome represents the proteolytic core complex for cytoplasmic protein
degradation that is involved in the activation and regulation of the immune
response. In this context, proteasome generates antigenic peptides for the MHC
class I pathway and activates NF-kappaB. In a recent analysis, we could identify
a frequent humoral autoimmune response directed against specific proteasomal
subunits in patients with autoimmune myositis, systemic lupus erythematosus and
primary Sjogren's syndrome. The outer ring subunit HC9(alpha3) was identified as
the predominant target of the anti-proteasome response in these entities. In
addition to the reactivity against HC9(alpha3), patients with primary Sjogren's
syndrome expressed a more polyspecific recognition pattern of proteasomal
subunits involving the active inner ring proteins. In follow-up analysis, anti
proteasome antibody titers revealed a correlation with disease activity in
patients with autoimmune myositis and systemic lupus erythematosus. The current
review summarizes recent data providing evidence that the 20S proteasome
represents an important target of the humoral autoimmune response in systemic
autoimmune diseases and extends insight into pathogenic aspects of these
diseases.
PMID- 11014976
TI - Role of apoptosis in pathogenesis and progression of renal diseases.
PMID- 11014977
TI - The obsession with high dietary protein intake in ESRD patients on dialysis: is
it justified?
AB - BACKGROUND: The belief that dialysis patients require a much higher intake of
protein than the average person is widely held among nephrologists and a recent
editorial review on the care of patients undergoing hemodialysis advised a
protein intake of at least 1.5 g/kg/day in this population. In theory, the
requirements for daily protein intake of dialysis patients should be the same as
normals plus whatever extra obligatory nitrogen losses are imposed by the
dialytic process. Since the average loss of protein and/or amino acids is about 8
g/day in peritoneal dialysis and 8 g per session in hemodialysis patients, the
daily intake of protein in dialysis patients needs to be increased only by this
small magnitude. METHODS: All the literature reporting on nitrogen balance data
on different protein intakes in chronic maintenance dialysis patients was
reviewed and analyzed. RESULTS: There were 3 balance studies addressing this
issue in hemodialysis patients and 6 in peritoneal dialysis patients. These data
show that dialysis patients are in nitrogen balance even with a protein intake as
low as 0.7 g/kg/day. CONCLUSIONS: The nitrogen balance data confirm that in
stable dialysis patients a safe requirement of protein intake is about 1 g/kg/day
and attempts at increasing protein intake beyond this value are not warranted.
The persistent recommendation of a high dietary intake of protein for dialysis
patients may reflect the influence of two other issues: the belief that dialysis
is a catabolic event, and the data showing an inverse correlation between protein
intake and outcome.
PMID- 11014978
TI - Urinary retinol-binding protein as a prognostic marker in the treatment of
nephrotic syndrome.
AB - We studied the urinary levels of retinol-binding protein (urRBP), an index of
proximal tubular dysfunction, in patients with nephrotic syndrome before and
approximately 2 months after the beginning of steroid therapy as a predictor of
response to therapy which included for some patients courses of immunosuppressive
drugs. Those patients with minimal-change disease, mesangial proliferative
glomerulonephritis, and focal-segmental glomerulosclerosis who had normal
pretreatment urRBP levels were responsive to treatment; occasionally, responsive
patients had an initially elevated urRBP level which normalized during treatment.
Contrariwise, those patients with abnormally high levels of urRBP which did not
normalize during treatment did not respond to treatment. The chance of a patient
with minimal-change disease, mesangial proliferative glomerulonephritis, or focal
segmental glomerulosclerosis and a pretreatment urRBP level equal to or >1.0 mg/l
being resistant to steroid treatment is 30 times that of a patient with a urRBP
level <1.0 mg/l and even higher, if we consider the levels obtained during
treatment.
PMID- 11014979
TI - Angiotensin-converting enzyme insertion/deletion polymorphism and prognosis of
IgA nephropathy.
AB - BACKGROUND/AIM: Well-known factors for a poor prognosis in IgA nephropathy (IgAN)
are hypertension, proteinuria, and renal insufficiency at the time of diagnosis.
Also hypertriglyceridemia and hyperuricemia seem to play a role in the
progression of IgAN. Angiotensin-converting enzyme (ACE) gene I/D polymorphism
has been associated with cardiovascular diseases and with progression of IgAN.
We, therefore, investigated the contribution of ACE gene I/D polymorphism in the
prognosis of IgAN and its association with the other risk factors affecting the
prognosis. METHODS: A total of 168 patients with IgAN were followed up for 6-17
(median 11) years from renal biopsy with respect to progression of renal disease
defined as elevation of serum creatinine above 125 microM (1.4 mg/dl) in men or
105 microM (1.2 mg/dl) in women and over 20% from the baseline level. In addition
to serum creatinine, the urinary protein excretion was evaluated at the time of
renal biopsy and at the assessment visit at the end of the follow-up period.
RESULTS: During the follow-up period, 26 (15%) patients showed progression of
renal disease. Patients with ACE genotype II had a more favorable course than
those with genotypes ID or DD. Although there were no significant differences
among the ACE genotypes with respect to proteinuria > or =1 g/24 h at the time of
renal biopsy, proteinuria > or =1 g/24 h was more frequent in patients with
genotypes ID or DD than in those with genotype II at the end of the follow-up
period. No associations were found between hypertension, serum lipids or serum
urate, and ACE genotypes. CONCLUSIONS: Our results show that patients with ACE
genotype II have a more favorable prognosis than those with genotypes ID/DD.
Secondly, proteinuria (> or =1 g/24 h) found in patients with genotype II at
diagnosis may improve, while in patients with genotypes ID/DD it is a more
constant feature.
PMID- 11014980
TI - Oral supplementation with gamma-linolenic acid extracted from Mucor
circinelloides improves the deformability of red blood cells in hemodialysis
patients.
AB - BACKGROUND: The development of abnormalities in red blood cell (RBC)
deformability in patients undergoing hemodialysis remains a major problem,
because it is related to peripheral microcirculation, oxygen supply, and various
complications in such patients. gamma-Linolenic acid (GLA; 18:3n-6), one of the
polyunsaturated fatty acids and a precursor of prostaglandin E(1), is reported to
have a favorable effect on the deformability of circulating blood cells in
diabetic patients. METHODS: In order to clarify the efficacy of GLA on RBC
deformability in 7 patients undergoing maintenance hemodialysis, we examined in a
pilot study the changes in the deformability of RBC and the changes in the
phospholipid fatty acid composition in both plasma and RBC membrane before and
after high-dose oral supplementation with GLA derived from Mucor circinelloides
for 12 weeks. RESULTS: Before supplementation, the micropore passage time of RBC
suspension, which is an indicator of RBC deformability, in these patients was
markedly longer than that in healthy control subjects. After administering GLA,
the prolonged passage time of the patients both rapidly and steadily decreased
and nearly reached control levels. Light microscopic observations of RBCs using
Giemsa stain revealed a decreased number of poikilocytes after supplementation.
An analysis of the fatty acid composition before treatment and 8 weeks after
starting the treatment showed the dihomo-gamma-linolenic acid (DGLA; 20:3n-6)
level in the plasma to have increased (p < 0.05), while the arachidonic acid (AA;
20:4n-6) concentration in the RBC membrane decreased (p < 0.05). The level of
DGLA in the RBC membrane, the level of GLA, and the ratio of GLA + DGLA/AA in
plasma and RBC membrane did not change significantly; however, these all tended
to increase. CONCLUSION: The results of this pilot study indicate that the oral
supplementation of GLA extracted from M. circinelloides improves the poor RBC
deformability in hemodialysis patients, partly by inducing changes in the
composition of fatty acids in plasma and RBC membrane.
PMID- 11014982
TI - Moderate metabolic acidosis and its effects on serum parameters in hemodialysis
patients.
AB - We screened the laboratory data of 50 chronic hemodialysis patients selected
randomly over a 21-month period to generate 158 data points which identified two
groups: (1) those with a predialysis total CO(2) concentration less than or equal
to 19 mEq/l (data A; n = 57) and (2) those with a predialysis total CO(2)
concentration greater than 19 mEq/l (data B; n = 101). Then, both groups were
compared for the following parameters: predialysis blood urea nitrogen (BUN),
serum phosphorus, uric acid, creatinine, and albumin concentrations, Kt/V, urea
reduction ratio, normalized protein catabolic rate, dry weight, ultrafiltration,
blood flow and dialysis flow rates, duration of dialysis treatment, and blood
pressure. Group data A had significantly higher predialysis BUN, phosphorus, and
uric acid concentrations than group data B. There were significant inverse
correlations between predialysis serum bicarbonate and predialysis BUN,
phosphorus, and uric acid concentrations. Although it is not clear what the long
term side effects of moderate metabolic acidosis are, we recommend its
correction.
PMID- 11014981
TI - Long-term knowledge retention following predialysis psychoeducational
intervention.
AB - BACKGROUND/AIMS: Early identification and predialysis psychoeducation are gaining
acceptance. Although research supports the immediate value of predialysis
interventions, long-term benefits remain unknown. We examined long-term knowledge
retention following a psychoeducational intervention. METHODS: 47 progressive
renal failure patients completed the Kidney Disease Questionnaire at baseline and
18, 30, 42, and 54 months after initiating renal replacement therapy (RRT; the
'longitudinal' sample). A larger cohort provided data at one or more of these
points (n = 132, 117, 101, and 70 at 18, 30, 42, and 54 months, respectively; the
'cross-sectional' sample). RESULTS: Initial knowledge gains among psychoeducation
recipients were followed by a significant knowledge advantage for three groups
throughout follow-up. Patients who received predialysis psychoeducation either
before or after starting dialysis demonstrated superior Kidney Disease
Questionnaire scores as compared with those identified before the initiation of
RRT who received the usual standard of practice. Patients identified after the
initiation of RRT and who received standard education, however, demonstrated the
same level of knowledge retention as produced by psychoeducation. The results
were identical across the longitudinal and cross-sectional samples. CONCLUSIONS:
Patient education produces important benefits in end-stage renal disease, but the
incremental value of early intervention remains to be demonstrated.
PMID- 11014983
TI - Constant, but not pulsed calcitriol suppresses hemodialysis patients' antigen
induced lymphocyte proliferation.
AB - BACKGROUND/AIMS: In vitro constant calcitriol [1,25-(OH)(2)D(3)] inhibits healthy
individuals' T lymphocyte proliferation at supraphysiological concentrations. In
contrast, among hemodialysis patients, intravenous 1,25-(OH)(2)D(3) pulse therapy
of secondary hyperparathyroidism has been shown to be even immunostimulatory. We
studied the effect of in vitro constant and intermittent 1, 25-(OH)(2)D(3) on
lymphocyte antigen response of hemodialysis patients. METHODS: Twelve
hemodialysis patients' peripheral blood mononuclear cells were stimulated with
purified protein derivative of tuberculin (12.5, 25 and 50 mg/l) or tetanus
toxoid (TT; 1,000, 5, 000 and 10,000 Lf/l, limit of flocculation) for 7 days.
Constant 1, 25-(OH)(2)D(3) was added to all cultures at concentrations of 0, 10(
10) or 0.25 x 10(-9) mol/l (0, 42 and 105 ng/l) and to half of the cultures
additionally as a 0.75 x 10(-9) mmol/l (315-ng/l) pulse on the 5th culture day.
RESULTS: TT-induced lymphocyte proliferation was statistically related to a
constant 1,25-(OH)(2)D(3) concentration (p = 0.001, analysis of variance). With
constant 1, 25-(OH)(2)D(3) concentrations of 0, 42 and 105 ng/l, the TT-induced
responses were 1.53, 1.44 and 1.40 log cpm, respectively (mean of TT
concentrations). The responses of the (additionally) pulse-treated cells [1.65,
1.50 and 1.40 log cpm; concentrations of constant 1, 25-(OH)(2)D(3) as above]
were similar to those of the nonpulsed cells. Thus constant, but not pulsed 1,25
(OH)(2)D(3) decreased the TT responses. On the purified protein derivative of
tuberculin response, neither constant nor pulsed 1,25-(OH)(2)D(3) had any
significant effect. CONCLUSIONS: The decline of TT response with constant 1,25
(OH)(2)D(3) corresponds with findings on immunosuppressive action of 1,25
(OH)(2)D(3) in previous studies done on normal subjects' cells. This was not seen
with intermittently applied 1,25-(OH)(2)D(3). These results support the previous
concept that intermittent 1,25(OH)(2)D(3) therapy is not immunosuppressive in
hemodialysis patients.
PMID- 11014984
TI - Decreased matrix metalloproteinase activity in the kidneys of hereditary
nephrotic mice (ICGN strain).
AB - Abnormalities of extracellular matrix (ECM) metabolism, i.e., overproduction
and/or inhibition of ECM breakdown, may contribute to progression of fibrotic
degeneration in the kidney. Earlier studies revealed that major ECM components,
type I, III, and IV collagens, etc., were accumulated in glomeruli and
tubulointerstitium in kidneys of Institute of Cancer Research (ICR) derived
glomerulonephritis (ICGN) mice which are a novel inbred strain of mice with a
hereditary nephrotic syndrome of unknown etiology and are considered to be a good
model of human idiopathic nephrotic syndrome. In the present study, we compared
the activities of matrix metalloproteinases (MMPs), a family of enzymes that
degrade ECM components, in the kidneys of aged ICGN mice and age-matched ICR mice
as normal controls. We biochemically measured interstitial collagenase (MMP-1),
gelatinase (MMP-2 and MMP-9), and stromelysin (MMP-3) activities in the kidney
tissues. Lower activities of MMP-1 and MMP-2 and MMP-9 were demonstrated in the
kidneys of ICGN mice as compared with those of ICR mice, but there were no
significant differences in the MMP-3 activities between these strains. These
results show that decreased MMP activities cause abnormal accumulation of ECM in
ICGN mouse kidneys.
PMID- 11014985
TI - Complement-mediated killing of mesangial cells in experimental
glomerulonephritis: cell death by a combination of apoptosis and necrosis.
AB - Immune system mediated, particularly antibody- and complement-mediated,
glomerular injury triggers glomerulonephritis (GN). To characterize complement
mediated cytotoxicity in GN, we assessed the process of mesangial cell death
induced by C5b-9 attack in Thy-1 GN. Cell injury was recognized morphologically,
and nuclear DNA breaks were confirmed by the DNA nick end labeling (TUNEL) method
as well as DNA gel electrophoresis. Thy-1 GN was induced in rats with anti-Thy
1.1 antibody injection. Mouse IgG (administered antibody) and rat C3 were
detected in all glomeruli within 5 min after antibody injection. Damaged
mesangial cells with condensed as well as TUNEL-positive nuclei could be observed
at 20 min and became prominent at 40-60 min. Ultrastructurally, damaged mesangial
cells contained condensed apoptotic nuclei from 40 to 60 min, whereas the
cytoplasm showed necrotic degeneration. This was followed by progressive lysis of
both nuclei and cytoplasm. The DNA 'ladder' pattern was observed by gel
electrophoresis of extracted DNA between 40 and 60 min and correlated with the
increased number of TUNEL-positive damaged mesangial cells. To examine the role
of complement in this form of cell death, complement depletion was induced in
rats by cobra venom factor. Complement-depleted rats showed no rat C3 deposition,
rare TUNEL-positive mesangial cells, rare ultrastructural degenerated mesangial
cells with apoptotic nuclei and necrotic cytoplasm, and no DNA 'ladder' pattern
on gel electrophoresis at 40 min, although prominent mouse IgG was seen in
glomeruli. To analyze milder forms of complement injury, a low dose of the
antibody was administered to rats with a normal complement level. A few TUNEL
positive mesangial cells were detected in the glomeruli which contained apoptotic
nuclei and necrotic cytoplasm. Our results indicate that an apoptotic death
mechanism accompanies cell necrosis in complement-mediated mesangial cell
destruction in GN and that this unusual form of cell death may represent a
combination of apoptosis-necrosis within the same cell. Complement injury
activates a 'death program' which in turn leads to irreversible damage of
mesangial cells and which may contribute to initiation and development of GN.
PMID- 11014986
TI - Effects of chronic hypoxia on renal PDGF-A, PDGF-B, and VEGF gene expression in
rats.
AB - BACKGROUND: There is evidence from in vitro studies to suggest that the genes of
platelet-derived growth factor (PDGF), and vascular endothelial growth factor
(VEGF) are, like the erythropoietin gene, regulated by oxygen tension. Hypoxia
induced stimulation of, for example, PDGF or VEGF might be involved in the
pathogenesis of acute or chronic renal failure and in renal 'inflammatory'
diseases (glomerulonephritis, vasculitis, allograft rejection). METHODS: Male
Wistar rats were exposed to chronic normobaric hypoxia (10% O(2), 90% N(2)) for 4
weeks. Additional groups of rats were treated with the endothelin receptor
antagonist LU13525 and the NO donor molsidomine. Renal mRNA levels of PDGF-A,
PDGF-B, and VEGF were semiquantitated using RNase protection assays. RESULTS:
Renal gene expression of PDGF-A and PDGF-B was neither affected by 2 or 4 weeks
of hypoxia nor by concomitant treatment with LU135252 or molsidomine. Chronic
hypoxia did also not change VEGF gene expression; however, concomitant treatment
with LU135252 increased all VEGF subtypes (188, 164, 120). CONCLUSIONS: The
findings of the present study suggest that renal PDGF and VEGF gene expression in
vivo during chronic hypoxia for 2 and 4 weeks is not sensitive to tissue hypoxia
in contrast to cell culture experiments. During chronic hypoxia with concomitant
blockade of endothelin receptors, all VEGF subtypes were increased, suggesting an
inhibitory action of endothelins with regard to renal VEGF gene expression.
PMID- 11014987
TI - Renal antioxidant enzymes and fibrosis-related markers in the rat adriamycin
model.
AB - Excessive generation of reactive oxygen intermediates can induce changes in the
cellular antioxidant defence system. In this study we examine the antioxidant
enzyme status and the expression of fibrosis-related marker proteins in the
Adriamycin model of chronic renal failure in the rat. Twenty weeks after
Adriamycin treatment, rats have overt nephrotic syndrome and renal failure with
development of tubulo-interstitial fibrosis and glomerulosclerosis. Lipids
accumulate in blood and in both glomeruli and tubulo-interstitial tissue. Desmin
and alpha-smooth muscle actin expression increases in glomeruli and in the tubulo
interstitial area. Renal cortex antioxidant enzyme activities are decreased 20
weeks after Adriamycin injection (to 41% for catalase, to 56% for total
superoxide dismutase and to 69% for glutathione peroxidase). The mRNA levels of
catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1 evaluated by
Northern blot are decreased by more than 50% for catalase, Cu/Zn-superoxide
dismutase and glutathione peroxidase-1. We conclude that in the rat Adriamycin
induced model of chronic renal failure with fibrosis, the combination of
decreased antioxidant enzyme status in renal cortex with high concentrations of
lipids in blood and renal tissue facilitates oxidative damage. Development of
fibrosis is paralleled by increased expression of desmin and alpha-smooth muscle
actin.
PMID- 11014988
TI - Investigation of the localization of dehydroepiandrosterone sulphotransferase in
adult rat kidney.
AB - Sulphotransferases are a family of enzymes involved in the metabolism and
detoxification of many compounds. Dehydroepiandrosterone (DHEA) sulphotransferase
(DHEA-ST), which catalyzes the sulphation of steroids such as DHEA, is present in
rat liver and adrenals. Sulphated steroids are present in urine, and many other
enzymes which catalyze detoxification reactions are found in the kidney. There
are not previous reports of DHEA-ST localization in adult kidney. The activity of
DHEA-ST was investigated in adult rat kidney by a radio-isotope assay with DHEA
as the substrate. Western blotting was used to assess protein expression, and the
localization of DHEA-ST was investigated by immunohistochemistry. The DHEA-ST
activity in rat kidney was found to be approximately four times less than that in
rat liver. In female kidney, the activity was 1.46 +/- 0.06 nmol/min/microg, and
in male kidney the activity was 1.29 +/- 0.09 nmol/min/microg. Investigation of
protein expression gave a single band at 35 kDa which signified the presence of
this enzyme in both male and female adult rat kidneys. Localization studies
showed positive staining at high intensity in the collecting ducts of the medulla
and in the S3 portion of the proximal convoluted tubule in the cortex. The
distribution within the proximal tubules was restricted to the brush border.
Reverse-transcriptase polymerase chain reaction showed DHEA-ST RNA expression in
adult rat kidney and liver. The presence of this enzyme and its location in the
kidney may suggest that in situ sulphation via DHEA-ST may play an important role
in the excretion of endogenous and exogenous compounds.
PMID- 11014989
TI - Proteinuria caused by lysozymuria mimics nephrotic syndrome.
PMID- 11014990
TI - 'Isolated' thrombocytopenia by splenic sequestration in hemodialyzed patients.
PMID- 11014992
TI - Pseudohypercreatininemia due to positive interference in enzymatic creatinine
measurements caused by monoclonal IgM in patients with Waldenstrom's
macroglobulinemia.
PMID- 11014991
TI - Evidence for accumulation of advanced glycation end products in acute renal
failure.
PMID- 11014994
TI - Mutagen accumulated in cyst fluid of acquired cystic disease of the kidney.
PMID- 11014993
TI - Streptococcus pneumoniae-induced acute renal failure in a neonate.
PMID- 11014995
TI - Nephrotic syndrome and amyloid A amyloidosis in a patient with Erdheim-Chester
disease.
PMID- 11014996
TI - The influence of steroid therapy in patients with IgA nephropathy.
PMID- 11014997
TI - Glomerular endothelial dysfunction and altered cytokines in severe nephrosis.
PMID- 11014998
TI - Intravenous low-dose iron administration in hemodialysis patients treated with
erythropoietin: 1-year follow-up study.
PMID- 11014999
TI - Serum ferritin and oxidative stress in patients undergoing hemodialysis.
PMID- 11015001
TI - What determines how satisfactory a size indicator is as a normalizing parameter
for small solute clearances in peritoneal dialysis?
PMID- 11015000
TI - Norfloxacin-induced acute interstitial nephritis.
PMID- 11015002
TI - Antioxidative treatment retards progression of idiopathic membranous nephropathy.
PMID- 11015003
TI - Effect of polymyxin B-immobilized fiber hemoperfusion on sepsis-induced
rhabdomyolysis with acute renal failure.
PMID- 11015004
TI - Hepatitis G virus markers in primary glomerulonephritis.
PMID- 11015005
TI - An increased serum level of parathyroid hormone is a risk factor for
aortosclerosis in hemodialysis patients.
PMID- 11015006
TI - Influence of anemia on treatment of malnutrition in patients on hemodialysis.
PMID- 11015008
TI - Serum KL-6 concentrations in hemodialysis patients with idiopathic interstitial
pneumonitis.
PMID- 11015007
TI - The concept of danger weight in intermittent peritoneal dialysis.
PMID- 11015009
TI - IL-1 receptor antagonist production by isolated mononuclear cells is a better
indicator of bioincompatibility of hemodialysis membranes than that by stimulated
whole blood.
PMID- 11015010
TI - r-HuEPO resistance and dialysate chloramine contamination in patients on
hemodialysis.
PMID- 11015011
TI - Do erythrocyte sedimentation rate and C-reactive protein levels have diagnostic
usefulness in patients with renal failure?
PMID- 11015012
TI - Increased urinary NAG excretion in hypertensives can decline with
antihypertensive treatment.
PMID- 11015013
TI - Allograft de novo membranous nephropathy complicating Alport's syndrome.
PMID- 11015014
TI - Pyelonephritis caused by mesalazine.
PMID- 11015015
TI - Tubulointerstitial changes are less important in membranoproliferative
glomerulonephritis than in IgA nephropathy.
PMID- 11015016
TI - Endothelial nitric oxide synthase gene polymorphism in patients with IgA
nephropathy.
PMID- 11015017
TI - Utility of serum and urinary transforming growth factor-beta levels as markers of
diabetic nephropathy.
PMID- 11015019
TI - Bilateral spontaneous perinephric hematoma: evaluation with CT and angiography
and successful conservative treatment.
PMID- 11015018
TI - Aldosterone influences serum magnesium in Gitelman syndrome.
PMID- 11015020
TI - Renal cholesterol microembolism: is steroid therapy effective?
PMID- 11015021
TI - Endothelial cell cytotoxicity and renal hypoperfusion in idiopathic nephrotic
syndrome.
PMID- 11015022
TI - Communication between acquired renal cysts and renal tubules.
PMID- 11015023
TI - Expression of receptor for advanced glycation end product mRNA by human
peritoneal mesothelial cells.
PMID- 11015024
TI - Comparison between the angiotensin II receptor antagonist candesartan cilexetil
and the angiotensin-converting enzyme inhibitor trandolapril in microalbuminuria
of patients with early diabetic nephropathy.
PMID- 11015025
TI - Low-density lipoprotein apheresis can improve type AA systemic amyloidosis.
PMID- 11015026
TI - Prune-belly syndrome in a geriatric patient.
PMID- 11015027
TI - Crescent formation in perimembranous-type renal amyloidosis associated with
multiple myeloma.
PMID- 11015028
TI - Depression and sleep disorders: clinical relevance, economic burden and
pharmacological treatment.
AB - A wide range of studies have been published over the past two decades that
involve the intersection of sleep EEG, insomnia, psychiatric illness (especially
depressive disorders) and psychopharmacology. Much of value has been discovered,
but there have also been false starts and contradictory results. There is in fact
strong evidence that insomnia is associated with medical and psychiatric illness
and that the sleepiness associated with insomnia is the cause of many accidents.
Thus, the direct (visits to doctors, cost of sleeping medication, complications
from use of these medications) and indirect (accidents, quality of life) costs of
insomnia are enormous and constitute a major public health problem in the
industrialized countries. Believing that it is now timely to assess the state of
this important research area, a consensus conference was convened on June 26-28,
1998, in Porto Cervo (Italy) to attempt to clarify the important issues and
findings on the clinical effect of the different classes of antidepressant drugs
on sleep quality in depression. The participants' consensus on some of the main
topics is presented with the hope that this discussion and analysis will
contribute to productive research in this important field.
PMID- 11015029
TI - Effects of antidepressants on gamma-aminobutyric acid- and N-methyl-D-aspartate
induced intracellular Ca(2+) concentration increases in primary cultured rat
cortical neurons.
AB - We investigated the effects of antidepressants on the intracellular Ca2+
concentration ([Ca2+]i) increases induced by gamma-aminobutyric acid (GABA) or N
methyl-D-aspartate (NMDA) in primary cultured rat cortical neurons using
fluorescence imaging. Acute treatment with imipramine inhibited GABA- and NMDA
induced increases in [Ca2+]i in a concentration-dependent manner. Doses of 30
microM clomipramine, desipramine, amoxapine and maprotiline also inhibited both
the GABA- and NMDA-induced [Ca2+]i increases significantly. Both inhibitory
effects of the five major antidepressants on the GABA- or the NMDA-induced
[Ca2+]i increases were well-correlated. Imipramine could inhibit significantly
high-K+-induced [Ca2+]i increases. Our previous study has already shown that the
GABA-induced [Ca2+]i increase involves a similar pathway to high-K+-induced Ca2+
influx. In conclusion, imipramine and several other antidepressants have acute
inhibitory effects on the GABA-, NMDA- and high-K+-induced [Ca2+]i increases,
suggesting that these inhibitory effects are not related to specific receptors.
One possibility is that these effects may be commonly mediated via part of the
high-K+-induced [Ca2+]i pathway.
PMID- 11015031
TI - Effect of paroxetine on thyroid hormone levels in severely depressed patients.
AB - There are very divergent appraisals of the effect of antidepressants on thyroid
parameters and their possible correlation with the response. Whereas there are
numerous investigations of tricyclic antidepressants, so far, there are only
limited data on the possible effect of serotonin-selective reuptake inhibitors on
neuroendocrine parameters. The present study showed a significant reduction of
11. 2% in thyroxine during treatment with 20 mg paroxetine in 25 severely
depressed patients.
PMID- 11015030
TI - Tissue-specific regulation of the peripheral benzodiazepine receptor by
antidepressants and lithium.
AB - Peripheral benzodiazepine receptors (PBR) have been identified in peripheral
organs as well as in brain glial cells. PBR differ from central benzodiazepine
receptors (CBR) in their lack of coupling to the gamma-aminobutyric acid
receptors and the chloride ion channels. We investigated the effect of 21 days
administration, followed by 7 days withdrawal, of fluvoxamine (10 mg/kg),
desipramine (10 mg/kg) and lithium carbonate (25 mg/kg) on PBR and CBR binding
characteristics in male Sprague-Dawley rats. All three agents significantly
increased PBR density in the testes and adrenals. All tested drugs induced a
significant decrease in PBR density in the kidney and liver. After withdrawal,
PBR density remained decreased in the liver in all three groups and in the
kidneys of the desipramine- and lithium-treated animals. In the cerebral cortex,
CBR density increased in response to all three agents, whereas PBR density
decreased significantly in response to desipramine and lithium carbonate. Chronic
treatment with fluvoxamine, desipramine and lithium carbonate is apparently
associated with a modulation in PBR expression in the testes, adrenals, kidneys,
liver and brain, and in CBR expression in brain. The relevance of these tissue
selective alterations to the antidepressive and/or anxiolytic effects of these
agents, or their adverse effects, still needs to be determined.
PMID- 11015032
TI - Zolpidem and promethazine in pre-anaesthetic medication. A pharmacopsychological
approach.
AB - This study dealt with the question: What are the effects of different doses of
the benzodiazepine-like agent zolpidem and the phenothiazine derivative
promethazine on mood in pre-anaesthetic medication? Subjects were 192 female and
male patients awaiting elective surgery. Two drugs were administered to the
patients in the evening before anaesthesia according to a 3 x 2 factorial
randomized double-blind design. The first drug factor was zolpidem (8.03 vs.
16.06 mg) versus placebo. These drugs were combined with the second drug factor,
either promethazine (50 mg) or placebo. In summary, the results confirm the
hypothesis that zolpidem 8.03 mg can induce paradoxical effects, especially of
anxiety, 1 h after application. When the dosage is doubled, no adverse effects
are found, but there are no effects different from placebo either. Men could
probably be described as a risk population for the adverse effects of zolpidem
8.03 mg. Furthermore, selective deactivating effects of promethazine 50 mg were
shown in this study. In addition to these anaesthesiological aspects, this study
showed promethazine to be useful as a research tool, suitable as a reference drug
to detect deactivating effects. The multidimensional self-report inventory
BSKE(EWL) (Befindlichkeitsskalierung durch Kategorien und Eigenschaftsworter)
detected the expected drug effects, indicating that this instrument is suitable
for further pharmacopsychological research.
PMID- 11015033
TI - Electrophysiologic analysis of antidepressant drug effects on the GABA(A)
receptor complex based upon antagonist-induced encephalographic power spectrum
changes.
AB - To better understand antidepressant drug effects on the GABA(A) receptor complex
(the GABA(A) receptor, chloride ionophore and benzodiazepine receptor), we
investigated how antidepressants influenced power spectrum changes induced by
pentylenetetrazol (PTZ), a chloride ionophore antagonist, in the rat hippocampal
electroencephalogram (EEG). In control recording, PTZ (27.5 mg/kg i. p.)
increased EEG power at frequencies under 12 Hz up to five times. After rats were
pretreated with imipramine, fluoxetine or trazodone for 7 days (10 mg/kg i.p.,
twice a day), PTZ could not increase EEG power to more than three times the power
before injection; this effect was not observed after pretreatment for 3 days.
These three antidepressants inhibit serotonin uptake, while two other
antidepressants, desipramine and nortriptyline, that inhibit norepinephrine
uptake failed to counter the PTZ effect. We concluded that antidepressants with
serotonergic effects enhanced the function of the GABA(A) receptor complex.
PMID- 11015034
TI - Effects of diazepam on auditory evoked potentials of rats elicited in a ten-tone
paradigm.
AB - The effect of diazepam on sensory gating was studied in rats by measuring
diazepam effects on auditory evoked potentials (AEPs) elicited in a ten-tone
paradigm. Trains of 10 repetitive tone-pip stimuli were presented. Rats (n = 8)
received 4 mg x kg(-1) diazepam subcutaneously or vehicle, counterbalanced over
two sessions. Diazepam decreased the amplitude of the middle-latency P30
component and increased the amplitudes of the late-latency N60 and P67
components. The increase in the late-latency components might be due to a
diazepam-induced decrease in arousal. Stimulus repetition decreased the
amplitudes of the middle-latency N18 and P30 components in both conditions. This
suggests that automated neuronal recovery functions underlying sensory gating
remain intact with diazepam. In the vehicle condition, the amplitude of the late
latency P67 decreased with stimulus repetition, but not in the diazepam
condition. This suggests a diazepam-induced decrease of behaviourally mediated
habituation.
PMID- 11015035
TI - Regulatory mechanisms in the retinal and choroidal circulation.
AB - The retina receives its nutrients from two separate circulations: retinal and
choroidal circulation. This short overview describes the determinants in the
regulation of these circulations. Retinal circulation is characterized by a low
blood flow while flow in the choroid is high. The choroidal circulation is mainly
controlled by sympathetic innervation and is not autoregulated. Retinal
circulation lacks autonomic innervation, shows an efficient autoregulation and is
mainly influenced by local factors. Local mediators released by endothelial cells
and surrounding retinal tissue also have a substantial role in the regulation of
retinal circulation.
PMID- 11015036
TI - nm23 Expression in choroidal melanoma.
AB - nm23 protein expression of choroidal melanoma was investigated to determine its
relationship with clinical and histopathological characteristics of the tumour.
Thirty-four consecutive choroidal melanoma patients were examined by
immunohistochemistry. Although age, sex, tumour cell type, tumour size,
pigmentation, necrosis, apoptosis and tumour lymphocytic infiltration were not
correlated with nm23 protein expression, tumours with low percentages of nm23
positive cells revealed higher nuclear grades and predominant mitotic figures.
nm23 may be associated with melanoma progression, but there is no proof that it
plays a role in the metabolic process of the tumour.
PMID- 11015037
TI - The suppressive effect of tecogalan sodium on in vitro angiogenesis via the
periendothelial proteolytic activities.
AB - The exact mechanisms of the angiostatic effect by tecogalan sodium (TS) remain
unclear. We examined the effects of TS on in vitro angiogenic activity,
proteolytic activity and proliferation of retinal vascular endothelial cells
(RECs). TS markedly inhibited the in vitro angiogenic activity of RECs although
the growth inhibition of RECs was small. TS apparently decreased the cell
associated urokinase-type plasminogen activator (uPA) activity and matrix
metalloprotease 1 (MMP-1) activity even in the presence of anti-bFGF IgG. Thus,
the suppression of the periendothelial matrix-degrading activities related to uPA
and MMP-1 is suggested to be another possible mechanism of the antiangiogenic
effect of TS, besides its prevention of bFGF REC binding which has previously
been reported.
PMID- 11015038
TI - Immobilization stress induces elevation of intraocular pressure in rabbits.
AB - The aim of this study was to test whether immobilization and intravenous volume
load as stressors influence the intraocular pressure in rabbits. Rabbits were
immobilized for 1 h in a horizontally placed plastic tube with an internal
diameter of 13.2 cm and a length of 33.2 cm. After immobilization, rabbits
received rapid intravenous drip infusion of 5% glucose solution, 20 ml/kg of body
weight, in 5 min. The intraocular pressure immediately after immobilization (11.2
+/- 3.0 mm Hg; mean and standard deviation) was significantly higher compared to
control rabbits without immobilization (9.2 +/- 1.0 mm Hg, Student's t test, p =
0.0462). This difference became significantly larger when volume load was exerted
on both groups of rabbits (22.7 +/- 5.6 versus 16.4 +/- 2.2 mm Hg, p = 0.0067).
Serum levels of cortisol, adrenaline, and noradrenaline were significantly
elevated after immobilization (p = 0.0002, p = 0.0271, p = 0.0296, respectively).
Venous pressure of the ear tended to increase in rabbits immediately after
immobilization (15.8 +/- 3.1 mm Hg) compared with control rabbits (8.5 +/- 2.3 mm
Hg), and the difference became significant when volume load was exerted on both
groups of rabbits (20.8 +/- 7.4 versus 9.2 +/- 4.8 mm Hg, p = 0.0211). In
conclusion, we clearly demonstrated that physical stress due to immobilization,
especially in combination with volume load, increased intraocular pressure in
rabbits.
PMID- 11015039
TI - Development of a completely encapsulated intraocular pressure sensor.
AB - A completely encapsulated intraocular pressure (IOP) sensor equipped with
telemetric signal and energy transfer is introduced integrated into a silicone
disc for implantation into the eye. After implantation into enucleated pig eyes
and into rabbit eyes in vivo, the IOP was recorded and compared to established
techniques of IOP measurement. Pressure chamber tests showed that the sensor
functioned correctly after biocompatible encapsulation in polydimethylsiloxane.
In vivo and in vitro tests in rabbit and pig eyes demonstrated that the implanted
system worked with the same precision as established techniques for IOP
determination. The correlation between the measurements with the implanted device
and pneumotonometry in several experiments was between 0.9 and 0.99. This device
serves as a functioning model for the realization of a telemetric IOP sensor for
integration into an artificial intraocular lens. Such a device will open new
perspectives, not only in the management of glaucoma, but also in basic research
for mechanisms of glaucoma.
PMID- 11015040
TI - Cholesterol content of focal opacities and multilamellar bodies in the human
lens: filipin cytochemistry and freeze fracture.
AB - Adult human lenses with focal opacities were processed for normal as well as
freeze fracture electron microscopy. Cholesterol was demonstrated using filipin
cytochemistry. Filipin cytochemistry in combination with freeze fracture revealed
that the amount of cholesterol in the normal fibre membranes was fully comparable
with the amount of cholesterol in the deviating membranes of the focal opacities
and the multilamellar bodies. As regards the cholesterol/phospholipid ratio, the
deviating membranes have the same state of maturation as the surrounding normal
lens fibre membranes, which implies that their synthesis is as highly coordinated
as the synthesis of the normal lens fibre membranes.
PMID- 11015041
TI - Universal opacity standard for Scheimpflug photography.
AB - PURPOSE: To develop a universal standard for comparison of the results from
different studies using Scheimpflug photography. MATERIAL AND METHOD: A
suspension including polystyrene spheres was selected as the universal standard.
The polystyrene suspension was diluted into 10 concentrations by adding
spectroscopic quality water. An artificial eye chamber was designed to hold the
diluted suspension for photography. Each concentration was photographed by both a
Topcon SL-45 slit-lamp camera and a Nidek EAS-1000 system. The intensity of back
scattered light was analyzed statistically. RESULTS: The relationship between the
concentration of the polystyrene suspension and the internal gray scale step
within the Topcon SL-45 camera can be described by a second-order polynomial. The
relationship between the concentration of the polystyrene suspension and the
measurement of the Nidek EAS-1000 system can also be expressed by a second-order
polynomial. The relationship between the Topcon SL-45 camera and the Nidek EAS
1000 system is linear. CONCLUSIONS: The results of lens nuclear opacity measured
with different Scheimpflug cameras can be compared using the method established
in the study. The linear relationship between the Topcon SL-45 and Nidek EAS-1000
systems can be used to convert measurements from one system to the other.
PMID- 11015043
TI - Inside Washington.
PMID- 11015042
TI - Serum methanol levels in subjects with or without optic nerve head disease.
AB - We evaluated serum methanol levels in subjects with or without optic nerve head
disease. Serum methanol levels were determined using gas chromatography in 71
patients with optic nerve head disease and in 127 subjects without optic nerve
head disease. Their ages ranged from 17 to 89 years. Serum methanol levels in 127
subjects without optic nerve head disease ranged from 0.12 to 3.86 microg/ml
(mean +/- standard deviation, 1.72 +/- 0.86 microg/ml). In the subjects without
optic nerve head disease, the differences in the levels between those with
cataract versus retinal detachment, men versus women, and between each age-group
(50-80 years) were not significant. The methanol levels in patients with optic
neuritis (n = 2), Wolfram syndrome (n = 1), Leber hereditary optic neuropathy at
the late stage (n = 2), retinitis pigmentosa (n = 23), and primary open-angle
glaucoma (n = 16) were less than 3.86 microg/ml. Methanol levels in 1 patient
with Leber hereditary optic neuropathy at the acute stage was 5.28 microg/ml. Of
10 patients with primary angle-closure glaucoma, 1 had a slightly elevated level
and 9 had levels less than 3.86 microg/ml. Of 17 patients with normal tension
glaucoma, 5 had methanol levels higher than 3.86 microg/ml, and 12 patients had
levels less than 3.86 microg/ml. The present study shows that serum methanol
levels in subjects without optic nerve head disease ranged from 0.12 to 3.86
microg/ml and were much lower than the levels that produce acute ocular symptoms
of methanol intoxication. It is possible that high serum methanol levels may play
a part in the acute stage of Leber hereditary optic neuropathy and normal tension
glaucoma in certain patients. It is unlikely that increased serum methanol levels
participate in primary angle-closure glaucoma.
PMID- 11015044
TI - People to People.
PMID- 11015045
TI - Coming Meetings.
PMID- 11015046
TI - Emergency nursing in perspective: mentoring, sharing, supporting.
PMID- 11015047
TI - Growing old is hard to do!
PMID- 11015048
TI - More on customer surveys run amok.
PMID- 11015049
TI - More on customer surveys run amok.
PMID- 11015050
TI - Experienced ED nurses have many options.
PMID- 11015051
TI - Experienced ED nurses have many options.
PMID- 11015053
TI - Experienced ED nurses have many options.
PMID- 11015054
TI - Experienced ED nurses have many options.
PMID- 11015055
TI - Zero waiting room time does not work when patients outnumber beds.
PMID- 11015059
TI - Dietary supplement or dangerous drug? Two case reports of gamma-butyrolactone
toxicity.
PMID- 11015060
TI - Geriatric assessment in the emergency department.
PMID- 11015061
TI - Elder neglect assessment in the emergency department.
AB - INTRODUCTION: Emergency departments are often the first point of contact for
elder neglect victims. The purpose of this article is to describe a pilot study
pertaining to the screening of patients and detection of elder neglect conducted
in a large metropolitan medical center emergency department. The research
question to be answered was, "Is it feasible for ED nurses to conduct accurate
screening protocols for elder neglect in the context of their busy practice?"
METHODS: During a 3-week period, 180 patients older than age 70 years (90% of all
possible elderly patients during the screening hours) were screened to determine
if they met the study criteria and could be enrolled into the protocol. RESULTS:
Thirty-six patients met the eligibility criteria to enroll in the study, and 7
patients screened positive for neglect by a home caregiver. The nurses were able
to screen and detect elder neglect with more than 70% accuracy, confirming the
research question. The true-positive rate was 71%, and the false-positive rate
was 7%. DISCUSSION: Elder neglect protocols are feasible in busy emergency
departments, and neglect can be accurately detected in the emergency department
when screening procedures are in place.
PMID- 11015062
TI - The millennial challenge: elder abuse.
PMID- 11015063
TI - Falls in the elderly: a multifactorial problem.
PMID- 11015064
TI - Teaching geriatric concepts to health care providers.
PMID- 11015065
TI - Activities and procedures performed by nurse practitioners in emergency care
settings.
AB - INTRODUCTION: Although nurse practitioners (NPs) have been practicing in
emergency care (EC) settings for at least 25 years, little is known about the
activities and procedures they perform. METHODS: A questionnaire was sent by
either by E-mail or US mail to a convenience sample of 96 subjects. These 96 NPs
were instructed to duplicate the questionnaire and distribute it to other NPs
they may know who also work in EC settings. The questionnaire contained 71
activities and procedures obtained from Clinical Procedures in Emergency Medicine
by Roberts and Hedges. The NPs were asked to rate the 71 activities and
procedures according to the frequency with which they performed them, where they
learned to perform them, and how important they believe it is that NPs in EC
settings know how to perform them. RESULTS: Seventy-two NPs in EC settings
responded. Fifty percent (n = 36) or more had performed 35 of the 71 activities
and procedures. Almost every NP (n = 71) had used fluorescein staining, and only
3 procedures--culdocentesis, venous cutdown, and insertion of pins for skeletal
traction--had never been performed. The majority of NPs learned to perform each
of the activities and procedures through on-the-job training and continuing
education courses. Fifty percent or more identified 56 activities and procedures
as being important for NPs to know how to perform in EC settings. DISCUSSION: The
results of this study indicate that whereas 50% or more of the NPs in EC settings
had performed 35 out of 71 activities and procedures, 50% or more indicated that
a larger skill set of 56 activities and procedures is believed to be needed for
practice.
PMID- 11015066
TI - Seen but not heard: battered women's perceptions of the ED experience.
AB - INTRODUCTION: A plethora of studies describe helping professionals' responses to
and actions directed toward battered women in the emergency department. However,
research that yields data regarding the clients' perceptions about their actual
experiences in the ED setting is sorely needed. The aim of this study was to
describe battered women's perceptions of their ED experience. METHOD: A
qualitative design, namely a phenomenologic approach, was used for this inquiry
to enable the women to express themselves in their own voices. Informants were
recruited from shelters for battered women. Women who had sought help for abuse
related injuries at a hospital emergency department within the past 12 months
were asked to participate. Methods used to collect data were in-depth,
individual, audiotaped interviews and demographic data sheets. Data analysis was
conducted using Colaizzi's (1978) procedural steps. RESULTS: Several categories
emerged as being descriptive of the women's perceptions of their ED experience.
Themes identified included the women's feelings during the visit, such as fear of
their partner, concern for children, and loneliness; the women's belief that the
ED staff do not understand abuse; satisfaction with treatment of physical
injuries but dissatisfaction with how the issue of abuse is managed; the
difficulty of disclosing the abuse because of fear, embarrassment, and a lack of
resources; and a request that health care professionals display compassion,
provide referrals, and offer options. DISCUSSION: The women's narratives
explicate their feelings during the ED visit and sensitize nurses to their
experience. The reports of dissatisfaction with the care they received in the
emergency department add to the validity of findings from previous studies that
have documented similar results and point to the need to examine and reshape the
delivery of care to abused women in the emergency department.
PMID- 11015067
TI - Designing and implementing a computerized tracking system: the experience at one
level I trauma center emergency department.
PMID- 11015068
TI - Hospice care in the emergency department: important things to remember.
PMID- 11015069
TI - Pediatric education for prehospital professionals.
PMID- 11015071
TI - Take care.
PMID- 11015072
TI - The Bowen case: who was the EMTALA villain--the doctor or the nurse, or neither?
PMID- 11015073
TI - Developing an ED training program: how to "grow your own" ED nurses.
PMID- 11015074
TI - Our new rapid treatment unit: an innovative adaptation of the "less than 24-hour
stay" holding unit.
PMID- 11015075
TI - Ergonomics, policy, and the ED nurse.
PMID- 11015076
TI - The elderly rape victim: stereotypes, perpetrators, and implications for
practice.
PMID- 11015077
TI - Trauma case management defined.
PMID- 11015078
TI - A 71-year-old man with syncope, respiratory distress, and hypotension.
PMID- 11015081
TI - Presidential address: dead wrong--thinking about...thinking... about...health
care.
PMID- 11015082
TI - Academic practice groups: strategy for survival.
AB - BACKGROUND: The mission of public academic health centers (puAHC) and their
affiliated practice groups (APG) focuses on teaching, research, and the clinical
care of at-risk populations. Resources to accomplish this mission, however, are
becoming scarce. For puAHC to survive and remain competitive, innovative
strategies will need to be developed by the APG. We hypothesized that the
integration of a surgical academic practice of the APG with a nonacademic
integrated health care delivery system (NAIDS) in a managed care environment
would benefit all involved. METHODS: A surgical academic practice was integrated
with a NAIDS in a 95% managed care market. Faculty alone provided care the first
year, and third-year residents were added the following year. To assess outcome,
we collected benefit and cost data for the 1-year period before integration and
compared them with the two, 1-year periods after integration. RESULTS: In the
second year of integration, revenues from the NAIDS referrals to the puAHC and
APG increased 89% and 150%, respectively. The NAIDS' general surgical and
endoscopy caseload increased by 25%. Additionally, there was a 92% reduction in
operating room technician cost with no increase in operating time per case.
Finally, the third-year resident experienced a caseload increase of 163%.
CONCLUSIONS: In an environment where resources are diminishing and managed care
consists of many large NAIDS that drive referrals and revenue, the integration of
a surgical academic practice with a NAIDS benefits all shareholders. Academic
practice groups that develop strategies that leverage their competitive advantage
will have the best chance of surviving in today's turbulent health care market.
PMID- 11015083
TI - Sustained infection induces 2 distinct microvascular mechanisms in the splanchnic
circulation.
AB - BACKGROUND: Altered intestinal blood flow during systemic inflammation leads to
organ dysfunction. Mucosal ischemia occurs during sepsis despite an increase in
portal blood flow. We hypothesized that separate mechanisms are active in the
large resistance and small mucosal microvessels to account for this dichotomy.
METHODS: Chronic infection was induced in rats by bacterial inoculation
(Escherichia coli and Bacteroides fragilis) of an implanted subcutaneous sponge.
Separate groups were studied at 24 and 72 hours after a single inoculation of
bacterium or 24 hours after a second inoculation (ie, 72 hours of sepsis). Time
matched controls were used for each group. Intravital microscopy of the terminal
ileum was used to assess endothelial-dependent vasodilation to acetylcholine (10(
9) to 10(-5) mol/L) in resistance (A(1)) and premucosal (A(3)) arterioles.
Threshold sensitivity (-log of 20% response dose) was calculated from dose
response curves for each animal. RESULTS: Vasodilator sensitivity to
acetylcholine in A(1) arterioles was significantly decreased at 24 hours, and
these changes persisted up to 72 hours after a single bacterial inoculation.
There was no change in the dilator sensitivity of A(3) arterioles after a single
inoculation. When there was a challenge with a second bacterial inoculation,
there was a reversal of the A(1) dilator response and an increase in A(3)
sensitivity. CONCLUSIONS: An initial septic event results in a decrease in
dilator reactivity in the resistance A1 arterioles that persists for at least 72
hours. A sustained septic challenge results in increased dilator reactivity in
both A(1) and A(3) vessels. This enhanced sensitivity during sepsis suggests that
more than 1 therapeutic approach to preservation of intestinal blood flow will be
necessary.
PMID- 11015084
TI - p21WAF1 expression is associated with improved survival after adjuvant
chemoradiation for pancreatic cancer.
AB - BACKGROUND: Cell cycle arrest after DNA damage is partly mediated through the
transcriptional activation of p21(WAF1) by the p53 tumor suppressor gene.
p21(WAF1) and p53 are both critical in maintaining cell cycle control in response
to DNA damage from radiation or chemotherapy. Therefore, we examined the role of
p21(WAF1) and p53 in the determination of outcome for patients who receive
radiation and/or chemotherapy for pancreatic cancer. METHODS: p21(WAF1) and p53
protein expression were determined (with the use of immunohistochemistry) in
specimens from 90 patients with pancreatic cancer. Forty-four patients underwent
surgical resection, and 46 patients had either locally unresectable tumors (n = 9
patients) or distant metastases (n = 37 patients). Seventy-three percent of the
patients who underwent resection and 63% of the patients who did not undergo
resection received radiation and/or chemotherapy. RESULTS: p21(WAF1) expression
was present in 48 of 86 tumors (56%) and was significantly (P<.05) associated
with advanced tumor stage. Median survival among patients with resected
pancreatic cancer who received adjuvant chemoradiation with p21(WAF1)-positive
tumors was significantly longer than in patients with no p21(WAF1) staining (25
vs. 11 months; P = .01). Fifty of 89 tumors (56%) stained positive for p53
protein. p53 overexpression was associated with decreased survival in patients
who did not undergo resection. CONCLUSIONS: Normal p21(WAF1) expression may be
necessary for a beneficial response to current adjuvant chemoradiation protocols
for pancreatic cancer. Alternate strategies for adjuvant therapy should be
explored for patients with pancreatic cancer who lack functional p21(WAF1).
PMID- 11015085
TI - A prospective surgical outcome study assessing the impact of parathyroidectomy on
symptoms in patients with secondary and tertiary hyperparathyroidism.
AB - BACKGROUND: To assess the impact of surgery on preoperative symptoms in secondary
(2 degrees ) and tertiary (3 degrees ) hyperparathyroidism (HPT) compared with
primary (1 degrees ) HPT. METHODS: Twenty-two patients with 2 degrees HPT and 10
with 3 degrees HPT were enrolled. Age-matched patients, 32 with 1 degrees HPT and
32 with thyroid disease were enrolled for comparison. An outcome questionnaire
documented symptoms expressed as the median symptom index score (MSIS)
preoperatively and at days 7 and 3 and 12 months postoperatively. RESULTS:
Preoperatively, the MSIS for the groups with 3 degrees, 2 degrees, and 1 degrees
HPT and thyroid disease was 225, 572, 372, and 146, indicating that patients with
HPT were more symptomatic than those in the thyroid group (P<.05). Patients with
1 degrees HPT had a decrease in their MSIS at day 7 (195, P<.05) and at 3 and 12
months (159 and 156). Patients with 3 degrees HPT also had a decrease in their
MSIS over time. Patients with 2 degrees HPT had a decrease in their MSIS at day 7
(469, P<.05); however, they remained more symptomatic at 3 and 12 months (410 and
355). CONCLUSIONS: Parathyroidectomy reduces many of the preoperative symptoms in
HPT. Patients with 1 degrees and 3 degrees HPT have a similar resolution of their
symptoms. Patients with 2 degrees HPT have an improvement in many of their
symptoms, although they remain more symptomatic at 1 year.
PMID- 11015086
TI - Surgical shunts and TIPS for variceal decompression in the 1990s.
AB - BACKGROUND: In the 1990s, liver transplantations and transjugular intrahepatic
portosystemic shunts (TIPS) have become the most common methods to decompress
portal hypertension. This center has continued to use surgical shunts for
variceal bleeding in good-risk patients who continue to bleed through endoscopic
and pharmacologic treatment. This article reports this center's experience with
surgical shunts and TIPS shunts from 1992 through 1999. METHODS: Sixty-three
patients (Child A, 43 patients; Child B, 20 patients) received surgical shunts:
distal splenorenal, 54 patients; splenocaval, 4 patients; coronary caval, 1
patient; and mesocaval, 4 patients. Sixty-two patients had refractory variceal
bleeding, and 1 patient had ascites with Budd-Chiari syndrome. Two hundred
patients (Child A, 24 patients; Child B, 62 patients; Child C, 114 patients)
received TIPS shunts. One hundred forty-nine patients had refractory variceal
bleeding, and 51 patients had ascites, hydrothorax, or hepatorenal syndrome. Data
were collected by prospective databases, protocol follow-up, and phone contact.
RESULTS: The 30-day mortality rate was 0% for surgical shunts and 26% for TIPS
shunts; the overall survival rate was 86% (median follow-up, 36 months) for
surgical shunts and 53% (median follow-up, 40 months) for TIPS shunts. For
surgical shunts, the portal hypertensive rebleeding rate was 6.3%; the overall
rebleeding rate was 14.3%. For TIPS shunts, the overall rebleeding rate was 25.5%
(30-day, 9.4%; late, 22.4%). There were 4 reinterventions for surgical shunts
(6.3%); the reintervention rate for TIPS shunts in the bleeding group was 33%,
and the reintervention rate in the ascites group was 9.5%. Encephalopathy was
severe in 3.1% of the shunt group and mild in 17.5%; this was not systematically
evaluated in the TIPS shunts patients. CONCLUSIONS: Surgical shunts still have a
role for patients whose condition was classified as Child A and B with refractory
bleeding, who achieve excellent outcomes with low morbidity and mortality rates.
TIPS shunts have been used in high-risk patients with significant early and late
mortality rates and have been useful in the control of refractory bleeding and as
a bridge to transplantation. The comparative role of TIPS shunts versus surgical
shunt in patients whose condition was classified as Child A and B is under study
in a randomized controlled trial.
PMID- 11015088
TI - Evolution of sentinel lymph node biopsy for melanoma at a National Cancer
Institute-designated cancer center.
AB - BACKGROUND: Sentinel lymph node biopsy (SLNB) has rapidly evolved into the
standard of care for clinically node-negative melanoma. Since adopting sentinel
lymph node (SLN) technology in 1993, we have periodically reviewed our
institution's results and made several modifications. METHODS: From January 1993
to December 1998, 182 patients with clinically node-negative primary cutaneous
melanoma underwent SLNB. Charts were retrospectively reviewed and assessed for
the technique for the identification of the SLN, the pathologic analysis, and the
use of intraoperative frozen section. RESULTS: The accuracy of SLN identification
improved from 91% to 100% with the combination of isosulfan blue dye and
radiolabeled colloid over isosulfan blue dye alone. Routine versus selective
lymphoscintigraphy identified 7 in-transit SLNs and increased detection of dual
nodal basin drainage (15%-27%). Identification of micrometastases in the SLN
increased from 14% to 24% after a modification of pathologic evaluation. The
positive SLN was the only involved node in most patients (80%). Intraoperative
frozen section had a sensitivity of 58% and was of benefit in only 13 of 124
patients (10%). CONCLUSIONS: Several modifications to the identification of the
SLNs and the detection of metastatic melanoma have improved our outcome with
SLNB. A careful, periodic review of results to identify areas for improvement at
each institution is crucial to the success of SLNB for melanoma.
PMID- 11015087
TI - Clinical outcomes and resource usage in 100 consecutive patients after off-pump
coronary bypass procedures.
AB - BACKGROUND: Cardiopulmonary bypass initiates a cascade of inflammatory processes
that may result in end-organ damage, leading to the increased prevalence of
noncardiac complications. Therefore, off-pump coronary artery bypass graft (OP
CAB) procedures have recently been introduced into clinical practice. METHODS:
This study was a case-controlled study that compared the outcomes and cost of 100
consecutive OP-CAB procedures with a control group of 100 contemporary matched
conventional coronary artery bypass grafting procedures. All operations were
performed by a single surgeon (J.H.L. ) and complete revascularization that used
off-pump techniques was achieved with the use of innovative exposure techniques
to the lateral and posterior wall vessels. RESULTS: An average of 3.1 grafts per
patient were performed in the OP-CAB group (range, 1-5). The incidence of
conversion to conventional coronary artery bypass grafting was 1%. The overall
mortality rate was 2.0%. There were no instances of stroke, renal failure, or
sternal infections in the OPCAB group. Thus, the OP-CAB group had a shorter
length of stay (6.1+/-2.5 versus 7.1+/-3.3 d; P =.003), with a corresponding
reduction in variable direct cost per case of 29% (P<.001). CONCLUSION: Our
experience suggests that OP-CAB procedures are feasible for most patients who
currently require complete revascularization. It is associated with very a low
morbidity rate and may represent the ideal revascularization strategy for
patients at high risk for undergoing cardiopulmonary bypass.
PMID- 11015089
TI - Neoadjuvant chemotherapy, radical resection with intraoperative radiation therapy
(IORT): improved treatment for gastric adenocarcinoma.
AB - BACKGROUND: Adenocarcinoma of the stomach and gastroesophageal junction results
in substantial morbidity, locoregional recurrence, and death. Surgical
procedures, even with adjuvant therapy, have not significantly improved survival.
This study evaluated the toxicity, response rate, locoregional control, and
survival of patients with locally advanced gastric cancer that was treated with
neoadjuvant multimodality therapy. METHODS: Patients with stage IIIA or early
stage IV gastric adenocarcinoma received neoadjuvant 5-fluorouracil, Leucovorin,
Adriamycin, and Cisplatin and underwent gastrectomy or esophagogastrectomy with
intraoperative radiotherapy (IORT; 1000 cGY) to the gastric bed and postoperative
radiation therapy. RESULTS: Nine of 15 patients (60%) with transmural extension
and/or nodal metastases received IORT. There were 2 pathologically complete
responses at the primary site. Eleven of 15 patients (73%) had tumor in
perigastric lymph nodes; however, 9 of 15 patients (60%) had mucin-filled nodes
without tumor cells. Neoadjuvant treatment did not increase operative morbidity
rates. Ten of 15 patients (67%) remain free of disease (median, 27 months; range,
6-60 months). Five patients died 13 to 41 months (median, 17 months) after
diagnosis. CONCLUSIONS: Neoadjuvant multimodality therapy with neoadjuvant 5
fluorouracil, Leucovorin, Adriamycin, and Cisplatin, radical resection with IORT,
and postoperative radiation therapy is safe, can downstage tumors, provides
improved locoregional control, and appears to cause significant tumor regression
that may result in long-term survival or cure.
PMID- 11015090
TI - Abdominal vena caval injuries: outcomes remain dismal.
AB - BACKGROUND: The mortality rate for abdominal vena caval injuries remains high. We
examined the experience of a level I trauma center to determine factors
significant to the outcome in these injuries. METHODS: Forty-seven patients were
identified in a retrospective review (1989 to 1999) of patients were identified
with abdominal vena caval injury. Data were analyzed by uni- and multivariate
methods, including logistic regression. RESULTS: Most of the individuals with
abdominal vena caval injuries were young male patients who were injured by
penetrating trauma and who were hypotensive on arrival. The severity of injury
and the number of organs injured was high. The overall mortality rate was 55%.
Nonsurvivors were more often hypotensive in the field with physiologic
derangement consistent with hemorrhagic shock. Type and location of injury as
well as method of repair were associated with death. Multiple regression analysis
revealed that prehospital initial systolic blood pressure and intraoperative
bicarbonate levels were independent predictors of survival. CONCLUSIONS: We
identified factors related to poor outcome, including suprarenal and retrohepatic
location of injury and variables that reflected the evolution of shock.
Management should include appropriate resuscitation and ultimately may require
novel operative techniques.
PMID- 11015091
TI - Liver transplantation from controlled non-heart-beating donors.
AB - BACKGROUND: The use of organs from non-heart-beating donors (NHBDs) has been
proposed as one way to increase the donor pool. However, few centers have
transplanted livers from NHBDs. We report here the results of 19 liver
transplants from controlled NHBDs. METHODS: From January 1993 through August
1999, 364 liver transplantations were performed from heart-beating donors (HBDs)
and 19 liver transplantations were performed from NHBDs. Donor and recipient
characteristics, posttransplant complications, and patient and allograft survival
were compared. RESULTS: No differences in hepatic artery, portal vein, or biliary
complications were noted between the groups. However, the rate of primary
nonfunction was higher in recipients of livers from NHBDs (10.5% vs. 1.3%; P =
.04). No difference in patient survival was seen between recipients of NHBDs or
HBDs (72.6% vs. 84.8%; P =.36); however, allograft survival was lower in
recipients who received livers from NHBDs (53.8% vs. 80.9%; P =.007).
CONCLUSIONS: Liver transplantation from controlled NHBDs results in similar
patient survival and post-transplant complications. However, primary nonfunction
was higher and allograft survival was less in recipients of livers from NHBDs.
The results of liver transplantation from controlled NHBDs are encouraging and
should continue to be cautiously pursued as one way to help alleviate the current
shortage of donor livers.
PMID- 11015092
TI - Efficacy of the laparoscopic approach for anterior lumbar spinal fusion.
AB - BACKGROUND: This study compares the immediate postoperative outcomes in patients
who undergo laparoscopic and open anterior lumbar spinal fusion and describes the
learning curve associated with the performance of this procedure. METHODS: The
charts of patients who underwent anterior lumbar spinal fusion between January
1995 and July 1999 were reviewed. Data pertaining to the operation and
postoperative course were analyzed and compared. RESULTS: Eighty-nine patients
underwent anterior lumbar spinal fusion. Fourteen patients were excluded; a full
analysis was performed on the records of the remaining 75 patients. Fifty-five
patients underwent an attempted laparoscopic procedure, and 20 patients underwent
an open procedure. The conversion rate was 38% (21/55 patients) in the group who
underwent the laparoscopic procedure. In the 34 patients whose laparoscopic
procedure was completed, there was significantly less blood loss and shorter
postoperative ileus, but the operative time was longer, when compared with
patients who underwent the open procedure. The laparoscopic procedures performed
in 1999 resulted in fewer conversions, less blood loss, and a shorter operating
room time, when compared with the laparoscopic procedures in 1998. CONCLUSIONS:
Laparoscopic anterior lumbar spinal fusion improves immediate postoperative
results when compared with open anterior lumbar spinal fusion.
PMID- 11015093
TI - Surgical treatment of anorectal complications in Crohn's disease.
AB - BACKGROUND: The purpose of our study was to elucidate features, surgical
procedures, and long-term results in patients with anorectal complications of
Crohn's disease. METHODS: Physical findings, surgical treatment, and long-term
outcome were recorded prospectively for 224 patients who had anorectal
complications of Crohn's disease between October 1984 and May 1999. RESULTS:
Presenting complications included abscess (n = 36), fistula-in-ano (n = 51),
rectovaginal fistula (n = 20), anal stenosis (n = 40), anal incontinence (n =
11), or a combination of features (n = 66). Twenty-four patients did not undergo
surgical treatment; the remaining 200 patients underwent 284 procedures.
Ultimately, 139 patients (62%) retained anorectal function; reasons for
proctectomy in the remaining 85 patients included disease (n = 66), extensive
fistular disease (n = 15), fecal incontinence (n = 2), and tight anal stenosis (n
= 1). Patients with rectal disease had a significantly higher rate of proctectomy
than patients with rectal sparing (77.6% vs. 13.6%, respectively, P<.0001). In
the absence of rectal involvement, patients with multiple complications had a
significantly higher rate of proctectomy than patients with single complications
(23% vs. 10%, P<.05). CONCLUSIONS: A wide spectrum of surgical techniques is
required for the management of the diverse anorectal complications of Crohn's
disease. Complete healing and control of sepsis can be achieved in the majority
of patients. Active rectal disease and multiple complications significantly
increase the need for proctectomy.
PMID- 11015094
TI - Primary gastrointestinal sarcomas: analysis of prognostic factors and results of
surgical management.
AB - BACKGROUND: This study was done to review the clinical presentation, surgical
management, and prognostic factors for primary gastrointestinal sarcomas.
METHODS: We reviewed medical records of 55 patients who were treated for primary
gastrointestinal sarcomas from 1981 through 1996. Mean follow-up time was 32
months. RESULTS: Clinical findings included gastrointestinal bleeding (51%),
palpable mass (36%), and abdominal pain (33%). The stomach was the most common
site of disease (53%), followed by the small intestine (33%). Tumors were high
grade in 76% of patients and low-grade in 24% of patients. Complete resection of
all gross disease was accomplished in 35 patients (64%), incomplete resection in
17 patients (31%), and biopsy only in 3 patients (5%). Adjacent organ resection
was required in 19 patients (35%). Overall actuarial survival was 22% (median
survival, 32 months). Unfavorable prognostic factors were incomplete resection,
high-grade histologic features, and tumor size of 5 cm or more (P<.05). En bloc
resection of contiguous organs did not adversely effect survival. In patients
with complete resections, tumor grade was the most important prognostic factor
(median survival, 55 months vs 19 months for low-grade vs high-grade tumors;
P<.05). CONCLUSIONS: Aggressive surgical resection, including en bloc resection
of locally advanced tumors, appears warranted. Despite complete resections,
patients with high-grade tumors remain at risk for recurrence.
PMID- 11015095
TI - Evaluating surgical competency with the American Board of Surgery In-Training
Examination, skill testing, and intraoperative assessment.
AB - BACKGROUND: Evaluation of surgical competency should include assessment of
knowledge, technical skill, and judgment. The purpose of this study was to
determine the relationship between the American Board of Surgery In-Training
Examination (ABSITE), skill testing, and intraoperative assessment. METHODS:
Postgraduate year 2 (PGY-2) and postgraduate year 3 (PGY-3) surgery residents (n
= 33) were tested by means of (1) the ABSITE, (2) skill testing on a laparoscopic
video-trainer, and (3) intra-operative global assessments during laparoscopic
cholecystectomy. The Pearson correlation was used to determine the correlation
between the ABSITE, skill testing, and intraoperative assessments. For the
comparison of PGY-2 and PGY-3 resident performance, Wilcoxon rank sum tests were
used. RESULTS: The ABSITE scores did not correlate with skill testing or
intraoperative assessments (not significant). Skill testing correlated with the
intraoperative composite score and with 4 of 8 operative performance criteria
(P<.05). The ABSITE scores and skill testing were not different for PGY-2 and PGY
3 residents (not significant). Intraoperative assessments were better in 5 of 8
criteria and the composite score for PGY-3 versus PGY-2 residents (P<.05), which
demonstrated construct validity. CONCLUSIONS: The ABSITE measures knowledge but
does not correlate with technical skill or operative performance. Residency
programs should use multiple assessment instruments to evaluate competency. There
may be a role for both skill testing and intraoperative assessment in the
evaluation of surgical competency.
PMID- 11015096
TI - A 32-year experience in 100 patients with giant paraesophageal hernia: the case
for abdominal approach and selective antireflux repair.
AB - BACKGROUND: Giant paraesophageal hiatal hernia (GPEH) presents a risk of
catastrophic complications that include massive bleeding, strangulation, and
perforation and should be repaired. Controversy persists as to the surgical
approach and whether an antireflux repair is required. METHODS: This study
reviews the experience with 100 patients with GPEH who underwent surgical repair
between 1967 and 1999. Eighty patients underwent an elective operation, and 20
patients underwent an emergency procedure for complications of GPEH. The
gastroesophageal junction was above the hiatus ("combined" hernia with sliding
component) in 23 patients and in the abdomen in 77 patients, including 3 patients
with a true parahiatal hernia. RESULTS: A thoracic approach was used in 18
patients, mostly early in our experience; postoperative gastric volvulus
requiring transabdominal repair developed in 2 patients. The remaining 82
patients underwent an abdominal repair, with temporary gastrostomy to prevent
gastric displacement in 75 patients; the hernial sac was resected, and the hiatus
was reconstructed in all of the patients. Thirty-five patients with reflux on
preoperative work up underwent a fundoplication, with gastroplasty in 2 patients
because of a short esophagus. No patient has experienced hernia recurrence.
Whereas symptomatic relief was excellent in all patients with elective repair,
mild reflux was present in 2 patients after emergency operation. There were no
deaths among the patients who underwent elective operation; there were 2 hospital
deaths among those patients who underwent emergency operation (10%). CONCLUSIONS:
GPEH should be repaired soon after recognition. Reflux should be evaluated before
the operation, and if present, fundoplication should be part of the repair along
with the reduction of the hernia, excision of the sac, gastropexy, and crural
closure. These are best achieved with an abdominal approach.
PMID- 11015097
TI - The risk assessment profile score identifies trauma patients at risk for deep
vein thrombosis.
AB - BACKGROUND: The identification of trauma patients at risk for the development of
deep venous thrombosis (DVT) at the time of admission remains difficult. The
purpose of this study is to validate the risk assessment profile (RAP) score to
stratify patients for DVT prophylaxis. METHODS: All patients admitted from
November 1998 thru May 1999 were evaluated for enrollment. We prospectively
assigned patients as low risk or high risk for DVT using the RAP score. High-risk
patients received both pharmacologic and mechanical prophylaxis. Low-risk
patients received none. Surveillance duplex Doppler scans were performed each
week of hospitalization or if symptoms developed. Hospital charges for
prophylaxis were used to determine the savings in the low-risk group. Statistical
differences between the risk groups for each factor of the RAP and development of
DVT were determined by the chi-squared test, with significance at a probability
value of less than .05. RESULTS: There were 102 high-risk (64%) and 58 low-risk
(36%) individuals studied. Eleven of the high-risk group (10.8%) experienced the
development of DVT (asymptomatic, 64%). None of the low-risk group was diagnosed
with DVT. Five of the 16 RAP factors were statistically significant for DVT.
Eliminating prophylaxis and Doppler scans in low-risk patients resulted in a
total savings of $18,908 in hospital charges. CONCLUSIONS: The RAP score
correctly identified trauma patients at increased risk for the development of
DVT. Despite prophylaxis, the high-risk group warrants surveillance scans.
Withholding prophylaxis in low-risk patients can reduce hospital charges without
risk.
PMID- 11015098
TI - Management of biliary tract disease in heart and lung transplant patients.
AB - BACKGROUND: Preexisting gallstones and pharmacologic alterations in both bile
lithogenicity and immune function may predispose organ transplant recipients to
the complications of biliary calculi. METHODS: Records of all 178 patients
undergoing heart, lung, or heart-lung transplantation at our institution between
1980 and 1998 were reviewed. Patients with biliary tract disease were grouped as
follows: group I, pretransplantation diagnosis and treatment; group II,
pretransplantation diagnosis and posttransplantation treatment; group III, normal
pretransplantation biliary tree with posttransplantation diagnosis and treatment;
group IV, unknown pretransplantation biliary status with posttransplantation
diagnosis and treatment. Comparison among groups was made with regard to
ultrasound findings, presentation, indication for operation, procedure, and
outcome. RESULTS: Of the 141 patients undergoing pretransplantation and/or
posttransplantation ultrasound surveillance, the prevalence of abnormal
ultrasonography was 36%. All patients in group I (n = 11) underwent elective
intervention without complication. Of the 14 patients (groups II through IV)
undergoing posttransplantation operation, intervention was mandated by acute
complications of biliary tract disease in 7. The mortality rate in these 7
patients was 29%. CONCLUSIONS: Cholecystectomy in the posttransplantation period
is often required emergently and has a high mortality. Posttransplantation
surveillance of the biliary tree is crucial because of the high rate of de novo
stone formation. All biliary calculi should be eradicated electively in stable
patients before transplantation and on diagnosis after transplantation.
PMID- 11015099
TI - All-artery multigraft coronary artery bypass grafting with only internal thoracic
arteries possible and safe: a randomized trial.
AB - BACKGROUND: The internal thoracic artery (ITA) bypass to the left anterior
descending coronary artery is of proven benefit in multigraft coronary artery
bypass. Total ITA grafts, if reoperation is averted by avoiding saphenous vein
grafts (SVGs), are attractive. The safety of the total ITA graft operation (all
ITA) is a concern. METHODS: A randomized trial of multiple-ITA bypass graftings
with the use of bilateral sequential ITA without SVGs was performed. Control
patients received 1 ITA plus SVG. Inclusion criteria were those used in the
Coronary Artery Surgery Study, extended to age 76 years, and any angina class,
except emergent. One hundred sixty-two patients were randomized (81 patients per
group) from January 1, 1990, to December 31, 1994. RESULTS: Baseline traits were
similar as were cross-clamp times, pump times, and number of arteries bypassed
(average, 4.3 arteries). Patients who received multiple ITA grafts had no
myocardial infarctions, per reference laboratory. One patient died, and 2
patients returned for bleeding. The ITA-SVG group had similar results. The all
ITA group experienced successful completion in 93% of cases. Complications did
not differ from control patients. CONCLUSIONS: Early and 5-year outcomes were not
different between the all-ITA group and the ITA with SVGs group. We believe
experienced surgeons can safely extend the ITA to multibypass coronary artery
bypass without use of SVG to achieve an all-ITA operation.
PMID- 11015100
TI - Laparoscopic splenectomy: outcomes and lessons learned from over 200 cases.
AB - BACKGROUND: In this study of laparoscopic splenectomy (LS), we evaluate
prospectively gathered perioperative patient data and review lessons learned in
the evolution of this procedure. METHODS: At 2 university medical centers between
November 1993 and March 2000, there were 203 patients (122 female patients and 81
male patients) who underwent LS after preoperative evaluation. RESULTS: LS was
successfully completed in 197 patients (97%). The mean operative time was 145.5
minutes and the length of stay averaged 2.7 days with 143 (70.4%) staying less
than 48 hours. The most common indication was idiopathic thrombocytopenic purpura
(ITP). Six patients required conversion to open splenectomy (OS), with only 2
conversions in the last 163 cases. No deaths were attributed to the procedure.
Complications occurred in 19 patients (9.3%). Thirty accessory spleens were
identified in 25 patients (12.3%). Seventeen patients (8.4%) underwent
concomitant procedures, most commonly cholecystectomy. CONCLUSIONS: LS by the
lateral approach is both safe and feasible in patients of all ages.
PMID- 11015101
TI - Long-term results of surgical repair of bile duct injuries following laparoscopic
cholecystectomy.
AB - BACKGROUND: Laparoscopic cholecystectomy (LC) is associated with an increased
incidence of bile duct injuries when compared with the open surgical technique.
Long-term results of repaired injuries and hepatic damage associated with chronic
biliary obstruction are lacking. METHODS: From Aug 1, 1991 until Dec 1, 1999,
there were 27 patients referred for management of complex biliary injuries that
occurred during LC. Patients underwent percutaneous transhepatic cholangiography
and placement of transhepatic catheters with computed tomography-guided biloma
drainage when indicated. On the basis of the cholangiography findings, patients
underwent Roux-en-Y hepaticojejunostomy (HJ) and liver biopsy or were treated
with nonsurgical interventions. RESULTS: Twenty-one of 27 patients (77. 8%)
underwent HJ, and 16 of these 21 patients (76.2%) also underwent hepatic biopsy.
In 1 patient, a recurrent stricture developed at 20 months after the initial
repair; and, in a second patient, an episode of cholangitis developed in the
postoperative period with the transhepatic catheters in place. Five of 16
patients (31.2%) demonstrated marked hepatic fibrosis with 4 (25%) of these
patients showing evidence of evolving cirrhosis at the time of HJ. CONCLUSIONS:
In this series with 55 months of follow-up, HJ repair of LC injuries was
associated with an initial 95.2% success rate and an ultimate success rate of
100%. Despite this, delayed referral, averaging 12 months, was associated with
significant hepatic injury in 5 of 16 (31.3%) patients who underwent biopsy.
PMID- 11015102
TI - Dynamic helical computed tomography scan accurately detects hemorrhage in
patients with pelvic fracture.
AB - BACKGROUND: The purpose of this study was to evaluate the use of dynamic helical
computed tomography (CT) scan for screening patients with pelvic fractures and
hemorrhage requiring angiographic embolization for control of bleeding. METHODS:
Patients admitted to the trauma service with pelvic fractures were identified
from the trauma registry. Data retrieval included demographics, hemodynamic
instability, Injury Severity Score, blood transfusion requirement, length of
stay, and mortality. CT scans obtained during the initial evaluation were
reviewed for the presence of contrast extravasation and correlated with
angiographic findings. Data are reported as mean +/- SEM, with P<.05 considered
significant. RESULTS: Seven thousand seven hundred eighty-one patients were
admitted from June 1994 to May 1999. A pelvic fracture was diagnosed in 660
(8.5%). Two hundred ninety (44.0%) dynamic helical CT scans were performed, of
which 13 (4.5%) identified contrast extravasation. Nine (69%) were
hemodynamically unstable and had pelvic arteriography performed. Arterial
bleeding was confirmed in all and controlled by embolization. Patients with
contrast extravasation had significantly greater Injury Severity Score, blood
transfusion requirement and length of stay. Sensitivity, specificity, and
accuracy of CT scan for identifying patients requiring embolization were 90.0%,
98.6%, and 98.3%, respectively. CONCLUSIONS: Early use of dynamic helical CT
scanning in the multiply injured patient with a pelvic fracture accurately
identifies the need for emergent angiographic embolization.
PMID- 11015103
TI - Hepatic resection: effective treatment for primary and secondary tumors.
AB - BACKGROUND: Hepatic resection is an accepted therapeutic modality for isolated
colorectal metastases (CRM) and primary hepatobiliary cancers (PC). Controversy
continues regarding the safety, efficacy, and appropriateness of resection for
noncolorectal metastases (NCM). METHODS: A retrospective review of 167 resections
in 160 patients was performed to evaluate the impact of demographics and
perioperative data on survival and recurrence. Statistical analyses were
performed by Student t test, analysis of variance, and Kaplan-Meier survival
estimates. RESULTS: Resections were performed for CRM, 110 of 167 (66%), NCM, 31
of 167 (19%), and PC, 26 of 167 (15%). The interval from primary to metastases
was significantly longer in the NCM group than the CRM group (34.7+/-45.1 vs.
18.7+/-23.7 months; P<.01). Mean number of lesions was not different between
groups; however, NCM were larger than CRM (5.9+/-4.5 vs 4.5+/-2.9 cm; P<.05).
Operative complications were significantly greater for PC (54%) versus CRM and
NCM (21% and 19%, respectively; P<.01), although length of stay was similar
between groups. Perioperative mortality was 2%. Actuarial survival at 1 year, 3
years, and 5 years was CRM 91%, 54%, and 40%, PC 75%, 60%, and 38%, and NCM 68%,
36%, and not available, respectively (CRM vs. NCM; P<.01 at 3 years).
CONCLUSIONS: Hepatic resection for primary and secondary malignancy can be
performed with minimal morbidity and mortality. Resection of NCM is associated
with a lower overall survival compared with CRM and PC. The disease-free interval
from resection of the primary to metastasectomy is prolonged and hepatic
recurrence infrequent after resection in the NCM group. These results suggest
that tumor biology is a critical determinant of outcome after hepatic resection
of primary and secondary hepatic tumors.
PMID- 11015104
TI - Safety and long-term efficacy of transduodenal excision for tumors of the ampulla
of Vater.
AB - BACKGROUND: Ampullary tumors should be resected because of the high incidence of
malignancy and the unreliability of preoperative endoscopic diagnosis.
Controversy exists about whether to perform a transduodenal excision (TDE) or a
pancreatoduodenectomy. This study evaluated the safety and long-term efficacy of
TDE. METHODS: The records of 21 patients with a pathologic diagnosis of ampullary
adenoma who underwent TDE were reviewed. Demographics, symptoms, pathologic
findings, and outcomes were analyzed and long-term follow-up was ascertained.
RESULTS: Twenty-one patients (mean age, 61 years) underwent TDE. Final pathology
showed adenoma in all patients including 1 (5%) with invasive cancer, 2 (9%) with
microinvasive cancer, 6 (28%) with high-grade dysplasia, and 1 (5%) with low
grade dysplasia. The overall survival was 85% (mean follow-up of 38 months). One
of 3 late deaths was likely related to disease progression. Sixteen of the 18
remaining patients (89%) had no evidence of tumor recurrence. One benign
ampullary recurrence was successfully treated endoscopically. One additional
patient developed an ampullary cancer and underwent pancreatoduodenectomy.
CONCLUSIONS: TDE of benign ampullary tumors, even those with varying grades of
dysplasia, can be performed with acceptable morbidity and low rates of
recurrence. Postoperative endoscopic surveillance is mandatory to identify
recurrent tumors.
PMID- 11015105
TI - Bilateral synchronous breast cancer: mode of detection and comparison of
histologic features between the 2 breasts.
AB - BACKGROUND: Bilateral synchronous breast cancer is uncommon (accounting for 1.0%
2.6% of all patients with breast cancer), and most physicians do not accumulate a
large personal experience of patients with this disease. We reviewed our
experience with patients with bilateral synchronous breast cancer, focusing on
the mode of detection and histologic features in the 2 breasts. METHODS: The
charts of patients who were treated at this institution for bilateral synchronous
breast cancer during the 15-year period of 1984 through 1999 were reviewed.
Information regarding age, mode of detection, histopathologic features,
treatment, and overall survival were analyzed. RESULTS: During the study period,
51 patients (all women) were treated at our institution for bilateral synchronous
breast cancer. This comprised 2.1% of all patients (n = 2382 patients) treated
for breast cancer during the same period of time. The first cancer was detected
by palpation in 81% and by mammography in 14%. The corresponding figures for the
contralateral cancer were 24% and 54%, respectively. The histologic type of
cancer was identical in the 2 breasts in 29 patients (57%) and was different
between the 2 breasts in 22 patients (43%). The overall 10-year survival rate was
63%. CONCLUSIONS: Bilateral synchronous breast cancer is often detected by
mammography and is frequently of the same histologic type as the index cancer. A
better awareness of the risk for this disease may help detect bilateral breast
cancer earlier.
PMID- 11015106
TI - Prone positioning for acute respiratory distress syndrome in the surgical
intensive care unit: who, when, and how long?
AB - BACKGROUND: We evaluated the effects of prone positioning (PP) on surgery and
trauma patients with acute respiratory distress syndrome (ARDS). METHODS:
Patients with ARDS were studied. Exclusion criteria were contraindications to PP.
Patients were evaluated in the supine position and after being turned to the PP.
After 6 hours, patients were returned to the supine position for 3 hours. One
hour after each position change, arterial and mixed venous blood was drawn and
analyzed for blood gases and pH, and hemodynamics were measured. RESULTS: Over 20
months, 27 patients met the criteria, and 20 of the patients were entered into
the study. On day 1, 18 of 20 patients (90%) responded with an increase in PaO(2)
during PP. On day 2, 16 of 17 patients (94%) responded; on day 3, 15 of 16
patients responded (94%); on day 4, 11 of 13 patients responded (85%); on day 5,
8 of 8 patients responded (100%); and on day 6, 4 of 5 patients responded (80%).
Pao(2)/Fio(2) and Qs/Qt were significantly improved (P<.05) during PP. There were
91 periods of PP, lasting 10.3+/-1.2 hours. Of 91 changes to PP, 78 changes (86%)
resulted in an improvement in Pao(2)/Fio(2) of more than 20%. CONCLUSIONS: PP
improves oxygenation in ARDS for 6 days with few complications.
PMID- 11015107
TI - Angioplasty does not affect subsequent operative renal artery revascularization.
AB - BACKGROUND: Although increased application of percutaneous renal artery
angioplasty and stenting has facilitated nonoperative renal revascularization,
patient outcomes after failed angioplasty are not established. METHODS: Renal
artery revascularization was performed in 31 patients (38 arteries) from 1993 to
1999. Twenty patients underwent primary surgical repair, and 11 patients
underwent secondary reconstruction after angioplasty (n = 7) or angioplasty and
stenting (n = 4). Before operation, all patients had severe hypertension (blood
pressure 166+/-5.2/92 +/- 2.7 mm Hg) that required an average of 3.0 +/- 0.2
medications for control. In addition, 12 patients (primary 45% vs secondary 27%;
P = NS) had evidence of renal insufficiency (creatinine > or =1.7 mg/dL).
RESULTS: There was no difference between primary and secondary procedures in the
length of hospital stay (12+/- 1.4 vs. 12+/-3.2 days; P = NS), major morbidity
(10% vs. 18%; P = NS) or perioperative mortality (overall mortality 2 of 31;
primary 5% vs secondary 9%; P = NS). The majority of patients demonstrated
improvement or cure of hypertension (primary 94% vs secondary 90%; P = NS) and
stable or decreased creatinine (primary 74% vs secondary 82%; P = not
significant). Overall survival (mean follow-up 22+/-3.5 months) was 89%+/-5.7%.
CONCLUSIONS: Although this surgical series does not address the true outcomes of
renal artery angioplasty, the results suggest that renal artery angioplasty does
not prejudice subsequent surgical outcomes in patients who are carefully followed
after angioplasty.
PMID- 11015108
TI - Simultaneous pancreas-kidney transplantation in the mycophenolate
mofetil/tacrolimus era: evolution from induction therapy with bladder drainage to
noninduction therapy with enteric drainage.
AB - BACKGROUND: In the past, enteric drainage or the omission of induction
immunotherapy has been shown to be predictive of suboptimal outcomes of
simultaneous pancreas-kidney (SPK) transplantation. We have reassessed the need
for bladder drainage and induction immunotherapy to optimize the outcome of SPK
transplantation. METHODS: One hundred consecutive recipients of SPK transplants
who received mycophenolate mofetil and tacrolimus immunosuppression were studied.
The first 50 recipients had bladder-drained pancreas allografts and received
induction immunotherapy. The results were compared with the next 50 recipients
who had enteric-drained pancreas allografts, which included a subgroup (n = 17
patients) who were randomized to receive no induction immunotherapy. RESULTS: The
1-year actuarial patient, kidney, and pancreas survival rates in the bladder
drainage group were 98.0%, 94.0%, and 94.0%, respectively. The 1-year actuarial
patient, kidney, and pancreas survival rates in the enteric-drainage group were
96.8%, 96.8%, and 89.4%, respectively. In the enteric-drainage group, the
incidence of rejection at 1 year was 6.1% in recipients who received induction
therapy versus 23.5% in recipients who did not receive induction therapy. The
average number of readmissions per recipient was 1.8 in the bladder-drainage
group versus 0.9 in the enteric-drainage group. CONCLUSIONS: Primary enteric
drainage of the pancreas allograft in recipients of SPK transplantation is the
preferred surgical technique in the tacrolimus/mycophenolate mofetil era.
PMID- 11015109
TI - Mild ductal atypia after large-core needle biopsy of the breast: is surgical
excision always necessary?
AB - BACKGROUND: The aim of the current study was to identify a select group of
patients with mild atypia who do not need surgical excision after large-core
needle biopsy (LCNB) of the breast. METHODS: Nineteen (70%) of 27 patients with
ductal atypia found on LCNB had subsequent surgical excision. These 19 patients
were retrospectively assigned to 3 groups according to the severity of the atypia
found, which was compared with the final pathologic specimen after surgical
biopsy. RESULTS: Cancer was identified through surgical biopsy in 6 (32%) of 19
patients. The severity of atypia seen on the LCNB specimen strongly correlated
with subsequent cancer identification (P<.01). Two (33%) of 6 patients in group 2
(true atypical ductal hyperplasia [ADH]) and 4 (80%) of 5 patients in group 3
(severe ADH, borderline ductal carcinoma in situ) had cancer after surgical
biopsy. No cancer was found after surgical biopsy in 8 patients in group 1 (mild
atypia, not meeting criteria for ADH). CONCLUSIONS: The results of this study
suggest that surgical excision can be avoided after LCNB of the breast in
patients with only mildly atypical lesions that do not meet criteria for ADH.
Patients with true ADH should continue to have surgical excision.
PMID- 11015110
TI - Intraoperative sestamibi scanning in reoperative parathyroidectomy.
AB - BACKGROUND: Reoperative neck exploration for hyperparathyroidism is often
difficult even for experienced surgeons. Recent advances in preoperative and
intraoperative localization techniques have improved successful resection rates.
This prospective study evaluates the accuracy and clinical utility of
intraoperative technetium 99m sestamibi scanning for localizing hyperfunctioning
parathyroid tissue in reoperative neck explorations. PATIENTS AND METHODS: Eleven
patients underwent reoperative neck exploration for hyperparathyroidism. Two
patients had 3 prior neck explorations, 1 had 2 prior neck explorations, and 8
patients had 1 prior neck operation. Preoperative studies included sestamibi
scintigraphy and ultrasound in all patients, magnetic resonance imaging in 4,
computed tomography scan in 3, parathyroid arteriogram in 1, and selective venous
sampling in 1. All patients underwent intraoperative technetium 99m sestamibi
scanning and parathyroid hormone assay. RESULTS: Preoperative technetium 99m
sestamibi scanning and ultrasound each successfully localized 7 of 11
hyperfunctioning glands (64%). Intraoperative technetium 99m sestamibi scanning
correctly localized 10 of 11 hyperfunctioning glands (91%). Intraoperative
parathyroid hormone assay confirmed successful excision of hyperfunctioning
tissue in all 11 patients. Postoperatively, all 11 patients had low-normal or
normal calcium levels. CONCLUSIONS: Intraoperative technetium 99m sestamibi
correctly localized 91% of hyperfunctioning glands compared with 64% localization
for preoperative technetium 99m sestamibi and preoperative ultrasound.
Intraoperative technetium 99m sestamibi scanning and parathyroid hormone
monitoring are useful in reoperative neck explorations for hyperparathyroidism.
PMID- 11015111
TI - Less invasive aortic surgery: the minilaparotomy technique.
AB - BACKGROUND: This study evaluated a less invasive technique for exposure of the
infrarenal aorta and its impact on the treatment of patients with abdominal
aortic aneurysms (AAA) or aortoiliac occlusive disease (AIOD), or both. METHODS:
Forty patients with AAA (26), aneurysmal extension into the iliac arteries (6),
or AIOD (8) were prospectively selected for minilaparotomy aortic exposure and
repair using a small periumbilical midline incision (< or =10 cm); intra
abdominal, nondisplaced retraction of the small bowel; and conventional hand-sewn
vascular anastomoses. Perioperative comparisons with a contemporary group of AAA
patients treated with long, open midline incision and extracavitary small bowel
retraction were made. RESULTS: There was no significant difference between the
minilaparotomy and open surgical control groups for operating room time;
intraoperative, perioperative morbidity; or mortality. Significant differences
were documented between the minilaparotomy and the control group with regard to
stay in the intensive care unit (days; 1.0+/-1.2 versus 1.8+/-1.5); return to
general diet (days; 3+/-1.3 versus 4.7+/-2.8); and length of stay (days; 4.9+/
1.8 versus 7.3+/- 3.4). CONCLUSIONS: Minilaparotomy exposure is safe and
effective for treatment of infrarenal AAA and AIOD. This technique maintains
quality outcome while reducing postoperative ileus, hospital stay, and resource
utilization.
PMID- 11015112
TI - Effects of an increased air gap on the in vitro interaction of wireless phones
with cardiac pacemakers.
AB - Several clinical and laboratory studies have demonstrated electromagnetic
interaction between implantable cardiac pacemakers and hand-held wireless phones
operated in close proximity. Current FDA and HIMA labeling guidelines indicate
that a minimum separation of 6 in (15 cm) should be maintained between a hand
held wireless phone and an implanted pacemaker. This separation requirement does
not distinguish between lateral locations on the chest and a perpendicular air
gap. Evidence is provided here for a substantially reduced separation threshold
when measured across an air gap rather than near the saline conductive media of a
simulated torso. Twenty pacemaker-phone combinations involving 6 pacemakers and 9
phones were evaluated in vitro under worst-case conditions with respect to phone
output power and pacemaker sensitivity. The phones represented CDMA, TDMA-11 Hz,
TDMA-22 Hz, TDMA-50 Hz, and TDMA-217 Hz digital wireless technologies. Small
increases in the perpendicular air gap between the phone and the saline surface
resulted in a dramatic reduction in interaction. Approximately half of the 208
test runs exhibiting interaction at an air gap of 1 cm no longer resulted in
interaction when the gap was increased to 2 cm. At a gap of 7.4 cm, the
percentage of runs with interaction decreased to 1.4%. The overall interaction
rate, considering a total of 8296 test runs from an earlier study, was less than
0.07% at a total perpendicular distance of 8.6 cm from the saline surface to the
phone antenna axis. The perpendicular distance threshold of 8.6 cm was
significantly less than the horizontal plane projection threshold of 19 cm
previously reported. This difference is a function of the electromagnetic field
coupling to the saline bath rather than field strength changes along the axis of
the phone antenna. The results have implications for those making recommendations
to pacemaker patients who may be unaware of this distinction.
PMID- 11015113
TI - Effect of low frequency, low amplitude magnetic fields on the permeability of
cationic liposomes entrapping carbonic anhydrase: I. Evidence for charged lipid
involvement.
AB - The influence of low frequency (4-16 Hz), low amplitude (25-75 mu T) magnetic
fields on the diffusion processes in enzyme-loaded unilamellar liposomes as
bioreactors was studied. Cationic liposomes containing
dipalmitoylphosphatidylcholine, cholesterol, and charged lipid stearylamine (SA)
at different molar ratios (6:3:1 or 5:3:2) were used. Previous kinetic
experiments showed a very low self-diffusion rate of the substrate p-nitrophenyl
acetate (p-NPA) across intact liposome bilayer. After 60 min of exposure to 7 Hz
sinusoidal (50 mu T peak) and parallel static (50 mu T) magnetic fields the
enzyme activity, as a function of increased diffusion rate of p-NPA, rose from 17
+/- 3% to 80 +/- 9% (P < .0005, n = 15) in the 5:3:2 liposomes. This effect was
dependent on the SA concentration in the liposomes. Only the presence of combined
sinusoidal (AC) and static (DC) magnetic fields affected the p-NPA diffusion
rates. No enzyme leakage was observed. Such studies suggest a plausible link
between the action of extremely low frequency magnetic field on charged lipids
and a change of membrane permeability.
PMID- 11015114
TI - Effect of low frequency, low amplitude magnetic fields on the permeability of
cationic liposomes entrapping carbonic anhydrase: II. No evidence for surface
enzyme involvement.
AB - Observations recently reported by our group indicate that combined 7 Hz
sinusoidal (B(acpeak) = 50 mu T) and parallel static (B(dc) = 50 mu T) magnetic
fields can induce a significant increase in diffusion rate of substrate across
carbonic anhydrase (CA)-loaded liposomes (DPPC:Chol:SA). A direct involvement of
charges of stearylamine (SA) on the lipid membrane surface was also demonstrated.
Kinetic studies showed that CA was mainly entrapped in liposomes at 5:3:2 molar
ratio, although a small amount (17%) of enzyme was also located on the external
surface of these cationic liposomes. In this paper we report steady state kinetic
studies on this latter CA after ELF-EMFs exposure. No difference in the apparent
K(m) between exposed and sham samples was observed. On the contrary the apparent
V(max) was increased by approximately a factor of 2 after field exposure. In
spite of the proteolytic digestion of this external CA, a significant increase of
enzymatic activity, as a function of increase in the diffusion rate of substrate
across the lipid bilayer, was observed in the exposed samples. Based on these
results, a conformational change induced by the field on the CA located on the
external surface of 5:3:2 liposomes is excluded as an explanation for our
previous observations, supporting the primary role of bilayer SA in the
interaction with ELF. A model of ELF interaction, based on the Larmor precession
theory, explaining the physical phenomenon induced on the dipole of SA has been
developed.
PMID- 11015115
TI - Recommended minimal requirements and development guidelines for exposure setups
of bio-experiments addressing the health risk concern of wireless communications.
AB - The evidence currently available on the potential health effects from
electromagnetic field (EMF) exposure has been largely judged as being too
tentative and inadequate to meet criteria for assessing health risks. Some of the
main reasons for these shortcomings lie in the incomplete description of the
exposure and poorly characterized dosimetry. Well-defined exposure conditions are
essential to obtain reproducible and scientifically valuable results. To
facilitate the development of optimized setups for specific bio-experiments, this
paper lists basic requirements and provides development guidelines for
evaluation, optimization, construction, and verification of exposure. In
addition, definitions of minimum performance requirements for setups addressing
the health risk concern of wireless communications are suggested.
PMID- 11015116
TI - No mutagenic or recombinogenic effects of mobile phone fields at 900 MHz detected
in the yeast Saccharomyces cerevisiae.
AB - Both actively growing and resting cells of the yeast Saccharomyces cerevisiae
were exposed to 900-MHz fields that closely matched the Global System for Mobile
Communication (GSM) pulsed modulation format signals for mobile phones at
specific absorption rates (SAR) of 0.13 and 1.3 W/kg. Two identical anechoic test
chambers were constructed to perform concurrent control and test experiments
under well-controlled exposure conditions. Using specific test strains, we
examined the genotoxic potential of mobile phone fields, alone and in
combination, with a known genotoxic compound, the alkylating agent methyl
methansulfonate. Mutation rates were monitored by two test systems, a widely used
gene-specific forward mutation assay at CAN1 and a wide-range assay measuring the
induction of respiration-deficient (petite) clones that have lost their
mitochondrial function. In addition, two further assays measured the
recombinogenic effect of mobile phone fields to detect possible effects on
genomic stability: First, an intrachromosomal, deletion-formation assay
previously developed for genotoxic screening; and second, an intragenic
recombination assay in the ADE2 gene. Fluctuation tests failed to detect any
significant effect of mobile phone fields on forward mutation rates at CAN1, on
the frequency of petite formation, on rates of intrachromosomal deletion
formation, or on rates of intragenic recombination in the absence or presence of
the genotoxic agent methyl methansulfonate.
PMID- 11015117
TI - Neural and behavioral teratological evaluation of rats exposed to ultra-wideband
electromagnetic fields.
AB - Several investigators have reported teratologic effects of electromagnetic field
exposure. The majority of these studies have been performed at levels of exposure
that could produce substantial heating of the animals. New and unique sources of
ultra-wideband (UWB) electromagnetic fields are currently being developed and
tested that are capable of generating nonthermalizing, high-peak-power, microwave
(MW) pulses with nanosecond (ns) pulse widths, picosecond (ps) rise times, and an
UWB of frequencies. Our study was performed to determine if teratological changes
occur in rat pups as a result of (i) daily UWB exposures during gestation days 3
18, or (ii) as a result of both prenatal and postnatal (10 days) exposures. Dams
were exposed either to (i) UWB irradiation from a Kentech system that emitted a
55 kV/m-peak E field, 300 ps rise time, and a 1.8 ns pulse width, average whole
body specific absorption rate 45 mW/kg; (ii) sham irradiation; or (iii) a
positive control, lead (Pb) acetate solution (2000 microg/ml) continuously
available in the drinking water. Offspring were examined for ontogeny (litter
size, sex-ratios, weights, coat appearance, tooth-eruption, eye-opening, air
righting, and ultrasonic stress vocalizations). Male pups were tested on various
performance measures (locomotor, water-maze learning, and fertilization
capabilities). The pups postnatally exposed were examined for hippocampal
morphology and operant behavior. Behavioral, functional, and morphological
effects of UWB exposure were unremarkable with these exceptions: (i) The UWB
exposed pups emitted significantly more stress vocalizations than the sham
exposed pups; (ii) the medial-to-lateral length of the hippocampus was
significantly longer in the UWB-exposed pups than in the sham-exposed animals;
(iii) male offspring exposed in utero to UWB mated significantly less frequently
than sham-exposed males, but when they did mate there was no difference in
fertilization and offspring numbers from the sham group. There does not appear to
be a unifying physiological or behavioral relationship among the significant
differences observed, and our findings could be due to the expected spurious
results derived when a large number of statistical comparisons are made.
Significant effects found between our positive-controls and other groups on
numerous measures indicates that the techniques used were sensitive enough to
detect teratological effects. Bioelectromagnetics 21:524-537, 2000. Published
2000 Wiley-Liss, Inc.
PMID- 11015118
TI - The possible role of contact current in cancer risk associated with residential
magnetic fields.
AB - Residential electrical wiring safety practices in the US result in the
possibility of a small voltage (up to a few tenths of a volt) on appliance
surfaces with respect to water pipes or other grounded surfaces. This "open
circuit voltage" (V(OC)) will cause "contact current" to flow in a person who
touches the appliance and completes an electrical circuit to ground. This paper
presents data suggesting that contact current due to V(OC) is an exposure that
may explain the reported associations of residential magnetic fields with
childhood leukemia. Our analysis is based on a computer model of a 40 house
(single-unit, detached dwelling) neighborhood with electrical service that is
representative of US grounding practices. The analysis was motivated by recent
research suggesting that the physical location of power lines in the backyard, in
contrast to the street, may be relevant to a relationship of power lines with
childhood leukemia. In the model, the highest magnetic field levels and V(OC)s
were both associated with backyard lines, and the highest V(OC)s were also
associated with long ground paths in the residence. Across the entire
neighborhood, magnetic field exposure was highly correlated with V(OC) (r =
0.93). Dosimetric modeling indicates that, compared to a very high residential
level of a uniform horizontal magnetic field (10 mu T) or a vertical electric
field (100 V/m), a modest level of contact current (approximately 18 mu A) leads
to considerably greater induced electric fields (> 1 mV/m) averaged across
tissue, such as bone marrow and heart. The correlation of V(OC) with magnetic
fields in the model, combined with the dose estimates, lead us to conclude that
V(OC) is a potentially important exposure with respect to childhood leukemia
risks associated with residential magnetic fields. These findings, nonetheless,
may not apply to residential service used in several European countries or to the
Scandinavian studies concerned with populations exposed to magnetic fields from
overhead transmission lines.
PMID- 11015119
TI - Vitellogenin of Blattella germanica (L.) (Dictyoptera, blattellidae): nucleotide
sequence of the cDNA and analysis of the protein primary structure.
AB - The cloning and sequencing of a cDNA of the vitellogenin gene from the cockroach
Blattella germanica is reported. It is 5,749 nucleotides long and encodes an
amino acid sequence of 1,862 residues (including a putative signal peptide of 17
residues). The vitellogenin sequence includes a long serine-rich stretch between
amino acids 322 and 349, and two other stretches between amino acids 1691 and
1740. The vitellogenin of B. germanica shows a notable similarity (between 32 and
42%) to those described in other insects, and its alignment shows a high number
of motifs conserved in all species, especially in the subdomains I-V. Non
parsimony methods (Neighbor Joining) of phylogenetic analysis of the insect
vitellogenin sequences gave a tree showing a topology that is, in general,
congruent with the currently accepted insect phylogenetic schemes. Arch.
PMID- 11015120
TI - Apoptosis in cultured midgut cells from heliothis virescens larvae exposed to
various conditions.
AB - We exposed midgut cells from primary cultures of Heliothis virescens larvae to
cell-free previously used medium, the Vaughn X and HyQ SFtrade mark media used
for serum-free culture of insect cell lines which do not support H. virescens
midgut cells, and to toxin from Bacillus thuringiensis. A statistically
significant increase in the percent of dying cells was counted in cell
populations in Vaughn X medium. Use of the TUNEL method to detect apoptosis
indicated a low rate (7.2%) of apoptosis in control cultures grown in Heliothis
medium, an increase to approximately 20% in previously used and HyQ SFtrade mark
media, and to approximately 45% of cells remaining after exposure to and initial
destruction by B. thuringiensis toxin. Apoptotic nuclei were predominant
(approximately 6%) in mature columnar cells in control cultures. Approximately 1%
of goblet, stem, and differentiating cells were apoptotic. However, apoptosis
rose to 12% in stem and differentiating cells exposed to used and unsuitable
medium. B. thuringiensis exposure to toxin for 2-3 days resulted in visible
membrane damage and necrosis, causing the death of 84% of the cells as measured
by both the TUNEL and Annexin methods. Some of the columnar cells and stem and
differentiating cells that remained also contained apoptotic nuclei. Stem and
differentiating cells normally replace dying mature cells in the midgut. Thus,
exposure of cultures of H. virescens midgut cells to adverse environments such as
unsuitable or poisonous media appeared to induce down-regulation of the cell
populations by apoptosis.
PMID- 11015121
TI - A cDNA encoding a chitinase from the epithelial cell line of chironomus tentans
(Insecta, diptera) and its functional expression.
AB - A cDNA coding for chitinase was isolated from Chironomus cells, which possesses
conserved regions I and II characteristic for family 18 chitinases, a C-terminus
enriched in Glu and Pro without the typical "PEST-region," putative glycosylation
sites, a reduced number of C-terminal cysteines, and no typical chitin binding
domain. Northern blots revealed one specific signal with an apparent size of 2.3
kb. The cDNA was expressed in the baculovirus/Spodoptera system as a His-tag
fusion protein, which was secreted as a functionally active enzyme into the
medium and could be separated from endogenous viral and Spodoptera-specific
chitinases.
PMID- 11015122
TI - Cloning of vitellogenin cDNA of the American cockroach, Periplaneta americana
(Dictyoptera), and its structural and expression analyses.
AB - A cDNA expression library constructed from poly (A)(+) RNA prepared from
vitellogenic female fat body cells of the American cockroach, Periplaneta
americana (Dictyoptera) was screened using a polyclonal antiserum against the 100
kD polypeptide(s) from the egg extract. A partial Vg cDNA clone was obtained and
sequenced. The 5' end portion of the cDNA was then obtained by the RACE method,
cloned, and sequenced. The combined complete Vg cDNA was 5,854 bp long and
contained a single ORF encoding 1,896 amino acids. The entire deduced amino acid
sequence was aligned confidently with those of the known insect Vgs. A GL/ICG
motif, a number of cysteines at conserved locations following this motif, and a
DGXR motif upstream of the GL/ICG motif were present near the C-terminal. The
chemically determined N-terminal amino acid sequence of the 170-kD polypeptide
from the egg extract completely matched the deduced sequence starting from just
after one of the consensus (RXXR) cleavage sites, indicating the occurrence of
post-translational cleavage in the fat body cells. The Vg gene begins to be
expressed in the 2-day-old adult female fat body cells but is never expressed in
ovaries or in male fat body cells. Hemolymph Vg was first detected by
immunoblotting in 4-day-old adult females, 2 days after the beginning of gene
expression. Western blot analysis of major yolk polypeptides in nine cockroach
species belonging to the two superfamilies, Blattoidea and Blaberoidea, using the
antisera against P. americana major yolk polypeptides showed that the
similarities in Vn antigenicity are basically limited to within a superfamily.
PMID- 11015123
TI - Relationship between case-control studies and the transmission/disequilibrium
test.
AB - Case-control studies provide a powerful approach for detecting disease
susceptibility loci that have only a weak to moderate impact on the risk of
disease, or markers that are in linkage disequilibrium with such loci. However,
since any association detected in a case-control study may result from
uncontrolled confounding, evidence for disease-marker associations obtained from
such studies must be confirmed by alternative methods. Since studies that use the
transmission/disequilibrium test or TDT are frequently employed to confirm
disease-marker associations detected in case-control studies, data are
increasingly available from both case-control studies and "TDT studies" of the
same disease-marker association. It would, therefore, be useful to have a single
measure of the magnitude of the disease-marker association that would allow for
comparison of results from these two study designs. Such a measure could also be
used to estimate minimum sample size requirements for TDT studies of previously
reported disease-marker associations. An obvious measure of the disease-marker
association in TDT studies is the frequency (T) with which heterozygous parents
transmit the putative, high-risk marker allele to affected offspring. In this
paper, it is shown that T can also be estimated from case-control data with a
minimum of assumptions, and that T is the critical parameter for determining
power and estimating sample sizes for the TDT.
PMID- 11015124
TI - Estimation of apolipoprotein E genotype-specific relative mortality risks from
the distribution of genotypes in centenarians and middle-aged men: apolipoprotein
E gene is a "frailty gene," not a "longevity gene".
AB - We developed a method to estimate genotype-specific average relative mortality
risk, R, from genotype distributions in cross-sectional studies of people
belonging to different age-groups, and applied the method to new data from a
study of apolipoprotein E genotypes (apoE) in 177 Danish centenarians and data
from a study of 40-year-old Danish men. Twenty-one percent of the centenarians
were epsilon 2-carriers (genotypes epsilon 2 epsilon 2 and epsilon 3 epsilon 2)
and 15% were epsilon 4-carriers (genotypes epsilon 4 epsilon 4 and epsilon 4
epsilon 3) compared to 13 and 29%, respectively, of the young men. The R-values
were 0.95 (95% CI 0.88 to 1.02) for epsilon 2-carriers and 1.13 (95% CI 1.05 to
1.22) for epsilon 4-carriers, using epsilon 3 epsilon 3- and epsilon 4 epsilon 2
genotypes as reference. Corresponding values for epsilon 4-carriers were obtained
by using published data from a French and a Finnish study of centenarians,
whereas the values for epsilon 2-carriers were about 0.90 with these data. The
method to estimate mortality risk and the results associate with the view that
the apoE gene is a "frailty gene." On the other hand, if odds ratios are used to
summarize data from studies of this kind, they are more impressive and may
propagate the misconception that apoE is a "longevity gene".
PMID- 11015125
TI - Combined linkage and linkage disequilibrium mapping for genome screens.
AB - Linkage analysis and association studies, two major approaches for genetic
studies of human diseases, are useful for mapping genes that are highly
penetrant, but both use only part of the information that is available for
mapping disease genes. Therefore, they provide limited utility when used alone.
In this report, we present combined linkage and linkage disequilibrium mapping
that simultaneously utilizes linkage and linkage disequilibrium information for
mapping human disease genes. Compared with the existing linkage analysis and
association study methods, this method has several advantages: 1) it has high
statistical power by a joint analysis of linkage and linkage disequilibrium for
localizing disease susceptibility loci: 2) it unifies the theory of linkage
analysis and linkage disequilibrium mapping, 3) it retains the general framework
for linkage analysis and, hence, can be easily incorporated into the existing
software for the linkage analysis. The proposed LLDM is applied to familial
hemophagocytic lymphohistiocytosis (FHL) disease.
PMID- 11015126
TI - Effects of early inhaled beclomethasone therapy on tracheal aspirate inflammatory
mediators IL-8 and IL-1ra in ventilated preterm infants at risk for
bronchopulmonary dysplasia.
AB - We tested the hypothesis that inhaled beclomethasone therapy for prevention of
bronchopulmonary dysplasia (BPD) reduces pulmonary inflammation. As part of a
randomized, placebo-controlled trial, interleukin-8 (IL-8) and interleukin-1
receptor antagonist (IL-1ra) concentrations in tracheal aspirates were measured
as markers of pulmonary inflammation. On study days 1 (baseline), 8, 15, and day
28 of age, samples were obtained from enrolled infants (birth weights <1,251 g,
gestational age <33 week, 3 to 14 days of age) who remained ventilated and had
not received systemic glucocorticoid therapy. Cytokine levels (pg/microg of free
secretory component of immunoglobulin A) were compared between groups. We
determined whether baseline cytokine levels modified treatment effect regarding
subsequent need for systemic glucocorticoid therapy or occurrence of BPD (age 28
days). Tracheal aspirates were obtained from 161 infants (77 receiving
beclomethasone, 84 receiving placebo). Median IL-8 levels were lower in
beclomethasone versus placebo infants on study days 8 (82.9 vs. 209.2, P < 0.01)
and 15 (37.4 vs. 77.4, P < 0.03) after controlling for antenatal glucocorticoid
therapy and maternal race. Median IL-1ra levels were lower in beclomethasone
versus placebo infants only on study day 8 (86.5 vs. 153.3, P < 0.01). Fewer
beclomethasone infants with baseline IL-8 levels in the interquartile range
required systemic glucocorticoid therapy (beclomethasone 30.6% vs. placebo 65.8%,
P < 0.01) or developed BPD (beclomethasone 42.4% vs. placebo 69.4%, P < 0.03). We
conclude that early-inhaled beclomethasone therapy was associated with a
reduction in pulmonary inflammation after 1 week of therapy. Beclomethasone
treated infants with moderately elevated baseline IL-8 levels received less
subsequent systemic glucocorticoid therapy and had a lower incidence of BPD than
nontreated infants.
PMID- 11015127
TI - Early changes in respiratory compliance and resistance during the development of
bronchopulmonary dysplasia in the era of surfactant therapy.
AB - Despite the availability of surfactant treatment, extremely low birth weight
(ELBW) infants continue to be at high risk of developing bronchopulmonray
dysplasia (BPD). Evidence suggests that pathologic changes occur within the first
few days of life. We hypothesized that the changes in early respiratory system
compliance and resistance in ELBW infants with or without hyaline membrane
disease (HMD) would correlate with BPD severity and aid in its prediction.
Respiratory system compliance (Crs) and resistance (Rrs) were measured at the end
of weeks 1, 2, 3, and 4 in 46 infants weighing 1,000 g or less at birth, using
the single breath airway occlusion method. Twenty-four infants had HMD and 22 did
not. Fifteen infants with and 10 infants without HMD developed BPD with
radiological changes and oxygen needs at 28 days. Twelve BPD infants required
supplemental oxygen beyond 36 weeks, defined as chronic lung disease (CLD).
Irrespective of whether the infant initially had HMD, the week 1 results showed
that infants who subsequently developed BPD had a significantly higher
respiratory system resistance than those who did not (P = 0.0014). Though week 1
compliance was lower, it was not statistical significant. Multiple logistic
models consisting of simple neonatal variables and week 1 respiratory mechanics
showed that Rrs was independently associated with subsequent BPD (P = 0.026) and
CLD (P = 0.016), while compliance was not. Prediction of CLD improved with the
inclusion of Rrs results as compared to prediction using clinical variables
alone. Throughout the 4-week study period, Rrs was significantly higher in BPD
infants than in those without BPD, and resistance was particularly abnormal in
those who had CLD or subsequently required corticosteroid treatment. These
observations provide rationale for interventions to prevent BPD within the first
week of life. Respiratory mechanics measurements could be useful in the
assessment of therapeutics in the current surfactant era.
PMID- 11015128
TI - Very low birthweight and asthma by age seven years in a national cohort.
AB - Several studies have suggested that very low birthweight (VLBW < 1500 g) is
associated with increased rates of respiratory problems in childhood and that the
presence of chronic lung disease further increases the risk. We aimed to assess
rates of asthma at 7-8 years of age in a national cohort of VLBW infants born in
1986 and for whom perinatal data were available. Two hundred ninety-nine former
VLBW children (96% of surviving children living in New Zealand) were assessed at
a home visit. Parents were asked a comprehensive questionnaire, including three
questions aimed at assessing morbidity from asthma: 1) was the child diagnosed as
having asthma before age 7 years; 2) was the child still experiencing asthma at
the age of 7 years; and 3) was the child prescribed daily medication for asthma
at the age of 7 years. Overall, 50% of the cohort had been diagnosed with asthma
before age 7, compared with 27% of a sample of New Zealand children assessed
contemporaneously in an international study; 32% had asthma at age 7, and 11%
were taking daily medication. All three categories of asthma were associated with
a family history of asthma, but there was no association with any perinatal
factors. A diagnosis of asthma before age 7 was more likely when the mother
smoked in pregnancy (P < 0.005) and currently smoked (P < 0.01), and trended so
when parents lacked high school qualifications and in Maori or Pacific Island
families (P < 0.10). In contrast, daily medication was more frequent when parents
had educational qualifications and in non-Maori or Pacific Island families (P <
0.05). On multiple logistic regression, a family history of asthma was a
significant predictor for any and current asthma (P < 0.001) and daily medication
(P < 0.05); maternal smoking in pregnancy was a significant predictor for any
asthma (P < 0.05); and non-Maori or Pacific Island ethnicity was a significant
predictor for asthma treatment (P < 0.05). We conclude that rates of childhood
asthma are high in this VLBW cohort, but the high prevalence appears to be
unrelated to perinatal factors, including respiratory morbidity. There are
suggestions that social factors contribute to both asthma risk and treatment.
PMID- 11015130
TI - Family history of atopy and clinical course of RSV infection in ambulatory and
hospitalized infants.
AB - Respiratory syncytial virus (RSV) infection can be severe in pediatric patients.
Risk factors for severe disease include age less than 6 months, prematurity,
preexisting heart or lung disease or malformations, gastroesophageal reflux, and
immunodeficiency. The aim of the present study was to investigate the influence
of family history of allergy on the clinical course of RSV infection in
ambulatory and hospitalized infants. In a retrospective study, 172 patients
younger than 12 months of age (99 inpatients and 73 outpatients) were enrolled.
Information was obtained from hospital charts and from questionnaires sent to
pediatricians. Inpatients had a significantly higher rate of atopy in their
family history than outpatients, 62% and 29%, respectively (P < 0.001).
Bronchiolitis was diagnosed more frequently in patients with an atopic burden
than those without, 89% versus 74%, respectively (P < 0.02). Inpatients with an
atopic family history had a significantly longer hospital stay than those without
such a history, 7.4 +/- 3.7 days and 6.1 +/- 2.3 days, respectively (P < 0.04).
Factors other than age that are considered a risk for severe infection with RSV
(prematurity, preexisting heart or lung disease or malformation, and
gastroesophageal reflux) were not confirmed in the present study. We conclude
that infants with a family history of atopy are at increased risk for severe RSV
infection as indicated by higher rates of hospitalization, longer hospital stay,
and more frequent occurrence of bronchiolitis.
PMID- 11015129
TI - School-based identification of asthma in a low-income population.
AB - The increase in the prevalence, morbidity, and mortality of asthma among children
over the last decade has been well documented, especially among low-income
minority children. Hypotheses for the increases in morbidity and mortality
include limited access to primary care services and the failure to recognize the
presence and severity of asthma. The University of Miami Pediatric Mobile Clinic
(Mobile Clinic) Asthma Intervention Program is designed to identify underserved
asthmatic children at school and offer them culturally sensitive care. Nine
elementary schools with low income, predominantly Hispanic and African-American
populations regularly served by the Mobile Clinic, were chosen for study
participation. All 5,800 students who were enrolled in kindergarten through third
grade were given letters at the time of registration by their homeroom teachers
about the asthma program. Caretakers who returned the questionnaire and reported
that the student had asthma symptoms were invited to have the student undergo a
medical evaluation in the Mobile Clinic. Over a 2-year period, caretakers of 423
students (7.3% of all students) expressed an interest in further evaluating their
child's respiratory health. Of these, we enrolled and evaluated 154 in the Mobile
Clinic's Asthma Intervention Program. The Mobile Clinic physicians identified 145
of the enrollees as having asthma. These results indicate that in elementary
schools serving predominantly low-income minority populations, a large fraction
of the asthmatic population (estimated prevalence, 6-10%) can be identified by a
school-based letter. Further, in a subset of asthmatic students (children of
interested caretakers), there is good agreement between caretaker responses and
physician diagnosis of asthma. Since school attendance is mandatory, school-based
methods may be an effective method for identifying low-income children with
asthma.
PMID- 11015131
TI - Limited agreement between written and video asthma symptom questionnaires.
AB - The prevalence of asthma remains difficult to determine with precision with no
absolute or "gold" standard for diagnosis. A recently developed video
questionnaire for epidemiological studies with less reliance on understanding
written questions provides another tool for determining prevalence and severity
of asthma. This report from the International Study of Asthma and Allergies in
Childhood (ISAAC) examines the agreement between the ISAAC video questionnaires
on respiratory symptoms and reported asthma. Between December 1993 and April
1995, 4952 children aged 13-14 years in two Canadian communities completed
sequentially the ISAAC written and video questionnaires at school. The agreement
between responses to the two questionnaires for reported wheeze ever, current
wheeze, wheeze on exercise, and nocturnal wheeze (the latter three questions
relating to symptoms in the last 12 months), and to any combination of the latter
three questions was examined in the full sample and in those reporting diagnosed
asthma, using concordance and kappa coefficients as measures of agreement. The
prevalences of wheeze ever, current wheeze, wheeze on exercise, and nocturnal
wheeze were significantly lower based on responses to the video questionnaire
compared with the written questionnaire in both regions in the full sample and in
those labeled as having asthma. Although concordance between video and written
questionnaires always exceeded 60% and often exceeded 70% for related questions,
agreement measured by the kappa statistic for each question was only fair to
moderate (kappa = 0.22-0.51). We conclude that the video questionnaire yields
lower reported prevalence rates for asthma symptoms, and that there is limited
agreement between responses to the two questionnaires that is not explained by
issues of language, culture, or literacy.
PMID- 11015132
TI - Bronchoalveolar lavage and esophageal pH monitoring data in children with
"difficult to treat" respiratory symptoms.
AB - Gastroesophageal reflux (GER) may be associated with chronic or recurrent asthma
like symptoms secondary to bronchoconstrictor reflexes and/or inhalation of
gastric content. The presence of lipid-laden alveolar macrophages has been
proposed as an index to establish the degree of gastric aspiration. We evaluated
20 children with "difficult to treat" respiratory symptoms and a clinical history
suggestive of GER. All children underwent 24-hr esophageal pH monitoring (pHm)
and fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). The amount of
lipid per single macrophage was determined by a semiquantitative method, using
fluorescence microscopy to detect Nile-Red-stained BAL cells and calculating a
lipid-laden macrophage index (LLMI). Eleven children had positive pHm recordings,
suggesting the presence of GER (pH-positive patients), and 9 had negative pHm
records (pH-negative patients). The pH-positive patients had higher percentages
of neutrophils and higher LLMI than the pH-negative children (P < 0.05). There
were no correlations between the pHm records and either % BAL neutrophils or LLMI
in pH-positive or pH-negative patients (P > 0.05; each correlation). In contrast,
a single correlation was found between % BAL neuytrophils and LLMI, both in the
pH-positive and in the pH-negative patients (r = 0.72, P = 0.02 and r = 0.71, P =
0.04, respectively). These data demonstrate that a significant proportion of pH
positive patients with respiratory symptoms have BAL abnormalities that suggest
airway inflammation and gastric content aspiration. However, the intensity of GER
as indicated by pH monitoring does not correspond with BAL data in all patients.
PMID- 11015133
TI - Serum lipase levels as a diagnostic marker in cystic fibrosis patients with
normal or borderline sweat tests.
AB - Patients with normal or borderline sweat test present a diagnostic challenge. In
spite of the availability of different methods such as genetic analysis and
measurements of nasal potential difference, uncertainty in diagnosing cystic
fibrosis (CF) in some patients still exists. Neonates with CF have high serum
lipase levels, which decline over time in pancreatic-insufficient patients,
whereas pancreatic-sufficient patients demonstrate high serum lipase levels
beyond infancy. Because patients with borderline or normal sweat test are almost
always pancreatic sufficient, this study was aimed to assess whether serum lipase
levels may be of help in establishing the diagnosis of CF in these patients.
Serum lipase levels were measured in 100 CF patients and in 17 healthy
individuals. Patients were grouped according to their genotype. Group A patients
(n = 70) carried two mutations previously found to be associated with a
pathologic sweat test and pancreatic insufficiency (delta F508, W1282X, G542X,
N1303K, S549R). Group B (n = 30) were compound heterozygote patients who carried
one mutation known to cause mild disease with borderline or normal sweat tests
and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 17 healthy
controls. Serum lipase levels ranged between 2 and 104.4 U/L (mean +/- SD 16.9 +/
14.7), 6.1-200 U/L (mean +/- SD 53.9 +/- 47.9), and 8.5-27.8 U/L (mean +/- SD
16.9 +/- 5.1) in Groups A, B, and C, respectively, with some overlapping between
groups. The distribution of lipase levels was significantly different in Group B
vs Groups A and C (P < 0.01). High lipase levels were found in 63.3% (19/30) of
Group B patients, but in only 4.3% (3/70) and 0% (0/17) of Group A and C,
respectively. Lipase levels were found to be inversely related to sweat chloride
concentrations (r = -0.19, P < 0.05). Patients with borderline or normal sweat
tests had high lipase levels, whereas low lipase levels were associated with
pathologic sweat tests. Our findings indicate that the serum lipase level is
genetically determined and that it has a useful role in the diagnosis of CF.
Thus, in patients with borderline sweat tests and high lipase levels, the
diagnosis of CF should be considered.
PMID- 11015134
TI - Perfluorochemical elimination from the lungs: effect of initial dose.
AB - Liquid-assisted ventilation with perfluorochemical (PFC) has been beneficial in a
variety of respiratory diseases in animals and humans. Although PFC evaporation
from the lungs is in part dependent on ventilation strategy and positioning,
guidelines for initial and replacement dosing are unclear. We hypothesized that
PFC evaporative loss over time is dependent on the size of the initial dose.
Juvenile rabbits (n = 18) were ventilated using constant animal position and
ventilator strategy. PFC (perflubron: LiquiVent ) was instilled endotracheally,
using four groups with initial doses of 2, 6, 12, and 17 mL/kg. A previously
described thermal detector that measures PFC in expired gas was used to calculate
loss rate, residual perflubron in the lung, and volume loss as a % of initial
fill volume. There was a significant dose, time, and dose-time interaction such
that evaporative loss was dependent on initial PFC volume and time after fill (P
< 0.05). Evaporative loss rate decreased earlier at lower doses. The percentage
of initial volume lost to evaporation over time was inversely related to dose and
could not be predicted by decreasing % PFC saturations, independent of dose.
Evaporative loss should be considered to optimize both the application of PFC to
the lung and replacement dosing during partial liquid ventilation.
PMID- 11015135
TI - Modern statistical techniques for the analysis of longitudinal data in biomedical
research.
AB - Longitudinal study designs in biomedical research are motivated by the need or
desire of a researcher to assess the change over time of an outcome and what risk
factors may be associated with the outcome. The outcome is measured repeatedly
over time for every individual in the study, and risk factors may be measured
repeatedly over time or they may be static. For example, many clinical studies
involving chronic obstructive pulmonary disease (COPD) use pulmonary function as
a primary outcome and measure it repeatedly over time for each individual. There
are many issues, both practical and theoretical, which make the analysis of
longitudinal data complicated. Fortunately, advances in statistical theory and
computer technology over the past two decades have made techniques for the
analysis of longitudinal data more readily available for data analysts. The aim
of this paper is to provide a discussion of the important features of
longitudinal data and review two popular modern statistical techniques used in
biomedical research for the analysis of longitudinal data: the general linear
mixed model, and generalized estimating equations. Examples are provided, using
the study of pulmonary function in cystic fibrosis research.
PMID- 11015136
TI - Teen-age smoking.
PMID- 11015137
TI - Wheezing as the sole clinical manifestation of cor triatriatum.
AB - Cardiac malformations involving low-pressure chambers (i.e., either of the atria)
are more often diagnosed later in life than lesions that involve high-pressure
systems such as ventricular septal defects or persistent ducti arteriosi.
Patients with congenital heart disease involving the atria may present only
symptoms suggesting lung disease. We report on a child with recurrent episodes of
wheezing, which did not respond to albuterol nebulizations and intravenous
corticosteroids; he was subsequently found to have cor triatriatum. When a
patient suffers from recurrent episodes of lower pulmonary infection and
wheezing, despite appropriate management for asthma, less common (including
cardiac) causes should be considered.
PMID- 11015139
TI - Selected abstracts
PMID- 11015138
TI - Status asthmaticus treated by high-frequency oscillatory ventilation.
AB - We present a 2.5-year-old girl in severe asthma crisis who clinically
deteriorated on conventional mechanical ventilation, but was successfully
ventilated with high-frequency oscillatory ventilation (HFOV). Although HFOV is
accepted as a technique for managing pediatric respiratory failure, its use in
obstructive airway disease is generally thought to be contraindicated because of
the risk of dynamic air-trapping. However, we suggest that obstructive airway
disease can safely be managed with HFOV, provided certain conditions are met.
These include the application of sufficiently high mean airway pressures to open
and stent the airways ("an open airway strategy"), lower frequencies to overcome
the greater attenuation of the oscillatory waves in the narrowed airways,
permissive hypercapnia to enable reducing pressure swings as much as possible,
longer expiratory times, and muscle paralysis to avoid spontaneous breathing.
PMID- 11015140
TI - Elementary school absenteeism and air pollution.
AB - This study assessed the association between ambient air pollution and daily
elementary school absenteeism in Washoe County, NV, between 1996 and 1998. All 57
elementary schools in Washoe County in northern Nevada were included in the data
set. There was a total of 27,793 student enrollments during this study period.
The daily average absence rate was 5.09% (+/-1.54%). Air pollutant values
including PM(10), O(3), and CO were obtained from seven air monitoring stations.
Weather variables were collected from five of seven stations and from the Western
Regional Climate Center. The daily average concentrations of PM(10), CO, and O(3)
were 32.44 microg/m(3), 2.73 ppm, and 37.45 ppb, respectively. Student
absenteeism was regressed on the three air pollutants, weather variables, and
other confounding factors, using autoregression analysis. After adjusting for the
effects of weather variables, day of the week, month, and holiday indicators, and
time trend, we found that CO and O(3) were statistically significant predictors
of daily absenteeism in elementary schools. For every 1.0 ppm and 50 ppb increase
in CO and O(3), the absence rate would increase 3.79% (95% CI 1.04-6.55%) and
13.01% (95% CI 3.41-22.61%), respectively. However, PM(10) values were negatively
correlated with school absenteeism.
PMID- 11015141
TI - Subchronic silica exposure enhances respiratory defense mechanisms and the
pulmonary clearance of Listeria monocytogenes in rats.
AB - Both Listeria monocytogenes infection and silica exposure have been shown to
significantly alter immune responses. In this study, we evaluated the effect of
preexposure to silica on lung defense mechanisms using a rat pulmonary L.
monocytogenes infection model. Male Sprague-Dawley rats were instilled
intratracheally with saline (vehicle control) or silica using either an acute
treatment regimen (5 mg/kg; 3 days) or a subchronic treatment protocol (80 mg/kg;
35 days). At 3 or 35 days after silica instillation, the rats were inoculated
intratracheally with either approximately 5000 or 500,000 L. monocytogenes. At 3,
5, and 7 days postinfection, the left lung was removed, homogenized, and cultured
on brain heart infusion agar at 37 degrees C. The numbers of viable L.
monocytogenes were counted after an overnight incubation. Bronchoalveolar lavage
(BAL) was performed on the right lungs, and BAL cell differentials, acellular
lactate dehydrogenase (LDH) activity and albumin content were determined.
Alveolar macrophage (AM) chemiluminescence (CL) and phagocytosis were assessed as
a measure of macrophage function. Lung-associated lymph nodes were removed, and
lymphocytes were recovered and differentiated. Preexposure to silica
significantly increased the pulmonary clearance of L. monocytogenes as compared
to saline controls. Exposure to silica caused significant increases in BAL
neutrophils, LDH and albumin, and lymph-nodal T cells and natural killer (NK)
cells in infected and noninfected rats. CL and phagocytosis were also elevated in
silica-treated rats. In summary, the results demonstrated that exposure of rats
to silica enhanced pulmonary immune responses, as evidenced by increases in
neutrophils, NK cells, T lymphocytes, and macrophage activation. These elevations
in pulmonary immune response are likely responsible for the increase in pulmonary
clearance of L. monocytogenes observed with preexposure to silica.
PMID- 11015142
TI - Estimation of dissolution rate from in vivo studies of synthetic vitreous fibers.
AB - Although the dissolution rate of a fiber was originally defined by a measurement
of dissolution in simulated lung fluid in vitro, it is feasible to determine it
from animal studies as well. The dissolution rate constant for a fiber may be
extracted from the decrease in long fiber diameter observed in certain
intratracheal instillation experiments or from the observed long fiber retention
in short-term biopersistence studies. These in vivo dissolution rates agree well
with those measured in vitro for the same fibers. For those special types of
fibers, the high-alumina rock wool fibers that could not be measured in vitro,
the method provides a way of obtaining a chemical dissolution rate constant from
an animal study. The inverse of the in vivo dissolution rate, the fiber
dissolution time, correlates well with the weighted half life of long fibers in a
biopersistence study, and the in vivo dissolution rate may be estimated
accurately from this weighted half-life.
PMID- 11015143
TI - Quantitative analysis of potential transfer of continuous glass filament from
eclipse prototype 9-014 cigarettes.
AB - This study was designed to determine if the Eclipse prototype 9-014 cigarettes,
which use a special form of continuous glass filament (CGF) as an insulator
around the carbon heat source, yield CGFs via mainstream smoke. A previously
developed method (Higuchi et al., 2000) that employed electrostatic precipitation
with a greater than 99% collection efficiency of mass-was used to capture CGFs
transferred to mainstream smoke. The cigarettes were smoked using an exaggerated
puffing condition more than twice the Federal Trade Commission (FTC) standard.
Prior to smoking, cigarettes were subjected to handling procedures that simulated
commercial shipping conditions. Using a modified standard addition method, and
utilizing a mixture of water and glycerol as a mock condensate, CGFs were
intentionally added to a series of (mock condensate) samples to develop knowledge
of CGF recovery efficiency. The linear regression model of the recovered CGFs
demonstrated a recovery efficiency of 86%. This efficiency rate was applied to
the number of CGFs recovered from samples of smoke condensate and associated
background samples. The number of CGFs in smoke condensate collected from the
Eclipse 9-014 prototype was approximately 0.32 +/- 0.17 CGFs per cigarette (+/-
standard deviation), including the background counts of CGFs, and 0.16 CGFs per
cigarette when corrected for background contributions. The number of CGFs found
in the smoke condensates for this prototype was statistically (p =.00031)
distinguishable from zero and background in these experiments. The low number of
CGFs seen in the transfer data from this prototype studied, the unique physical
characteristics of the filaments (e.g., controlled physical dimensions), and the
absence of biological activity of similar glass filaments/fibers indicate that
biologically significant exposure to the Eclipse smoker does not occur.
PMID- 11015144
TI - Safety assessment of continuous glass filaments used in eclipse.
AB - Eclipse is a cigarette that produces smoke by primarily heating, rather than
burning, tobacco. The Eclipse heat source assembly employs a continuous filament
glass mat jacket to insulate the heat source. The glass mat insulator is composed
of continuous glass filaments and a binder. The purpose of this article is to
address the potential toxicological significance of the continuous glass
filaments under the conditions of intended use. Transfer data and the unique
physical characteristics of the filaments demonstrate that significant exposure
of the smoker will not occur. The available environmental survey data clearly
demonstrate that Eclipse smokers are extremely unlikely to be exposed to
continuous glass filaments at a level that represents a biologically significant
increase over background exposure to glass fibers. The chemical composition of
the continuous glass filaments used in Eclipse is generally similar to C-glass
fiber compositions such as MMVF 11 that have failed to produce either tumors or
fibrosis in chronic inhalation studies conducted in rats. In vitro dissolution
data demonstrate that the continuous glass filaments used in Eclipse are more
soluble than biologically active fibers such as rock wool (MMVF 21) or asbestos.
However, the continuous glass filaments used in Eclipse were not as soluble in
simulated extracellular lung fluid as representative C-glass fibers (MMVF 10 and
MMVF 11). In brief, exposure of Eclipse smokers to continuous glass filaments is
extremely unlikely to occur at a level that may be construed to be of biological
significance.
PMID- 11015145
TI - Modified wick method using Weck-Cel sponges for collection of human rectal
secretions and analysis of mucosal HIV antibody.
AB - Weck-Cel sponges were examined for suitability as an absorbent material for
nontraumatic collection of rectal secretions in humans. Sponges were tested in
vitro and determined by quantitative enzyme-linked immunosorbent assay (ELISA) to
be capable of releasing 100% of absorbed albumin and all immunoglobulin subtypes
after treatment with detergent-supplemented buffer. Protein composition in rectal
secretions collected from normal women with dry sponges (DS) or with sponges
previously softened by moistening with saline (MS) was subsequently compared. DS
secretions showed evidence of contamination with blood and interstitial fluid
derived albumin, immunoglobulin G (IgG), and monomeric IgA. MS secretions
appeared to represent local mucosal secretions more accurately because they
contained negligible blood, a greater percentage of secretory IgA within the
total IgA, and both lower albumin/IgG ratios and more dramatic alterations in IgG
subclass distribution compared with corresponding serum. Anti-HIV IgG, IgM, IgA,
and antibodies with secretory component could be demonstrated by ELISA in rectal
secretions collected with moist sponges from 8 of 8, 1 of 8, 5 of 8, and 3 of 8
HIV-infected women, respectively. The data show that Weck-Cel sponges, if
premoistened, can be used to collect rectal fluids nontraumatically and to obtain
quantitative information about concentrations of immunoglobulins and specific
antibodies on rectal mucosal surfaces.
PMID- 11015146
TI - Absence of association between individual thymidine analogues or nonnucleoside
analogues and lipid abnormalities in HIV-1-infected persons on initial therapy.
AB - Changes in levels of triglycerides and cholesterol during antiretroviral therapy
raise concerns regarding an increased future risk of atherogenic disease and may
precede the appearance of fat redistribution. Hypotheses regarding the impact of
nucleoside analogues on adipocytes provide a possible explanation for metabolic
and clinical fat disturbances. It is unclear whether the choice of nucleoside
analogue combination or coadministration of nonnucleoside agents influences
change in lipids. We performed a cross-sectional analysis of 135 persons
receiving their first nucleoside analogue plus nonnucleoside-based combination
antiretroviral regimen for at least 1 month and for whom cholesterol and
triglyceride values were available on therapy. Univariate and multivariate
regression models were used to explore the relation between cholesterol and
triglycerides, as continuous variables with other variables. Both significant and
nonsignificant variables from univariate analyses were evaluated in multivariate
models to limit possible confounders. No association with drug choice was
observed, either when comparing thymidine analogues (stavudine or zidovudine),
all nucleoside analogue combinations or choice of either efavirenz or nevirapine
as nonnucleoside. Age and triglyceride levels were found in a multivariate
analysis to be associated with higher cholesterol. Only higher cholesterol was
associated with higher triglyceride levels. In conclusion, no differences were
observed between choice of drug or combination on cholesterol or triglyceride
values during therapy. Older individuals may be more likely to have elevated
cholesterol values.
PMID- 11015147
TI - Differences between women and men in adverse events and CD4+ responses to
nucleoside analogue therapy for HIV infection. The Aids Clinical Trials Group 175
Team.
AB - OBJECTIVE: To prospectively examine differences in baseline characteristics and
study outcomes between HIV-infected women and men during a clinical trial of
nucleoside analogue therapy. METHODS: ACTG 175 randomized HIV-infected patients
with CD4+ counts between 200 and 500 cells/mm3 to one of four nucleoside analogue
regimens: zidovudine (ZDV), didanosine (ddI), ZDV + ddI, or ZDV + zalcitabine
(ddC). Differences in time to first dose modification, voluntary withdrawal,
development of toxicity and symptomatology, and AIDS progression were compared by
gender. RESULTS: The study included 438 women and 2029 men. Baseline values of
HIV RNA plasma concentrations were significantly lower for women (0.3 log10) than
men in a subset of patients in whom assays were taken and this difference
persisted after adjustment for CD4+ count. Women reported reducing dosage and
discontinue ddI-containing regimens more frequently than men did; adjustment for
weight did not completely explain this difference. Women were at lower risk than
men for progression to a study endpoint (19% of women versus 24% of men; p
<.0001). Among those antiretroviral-naive study subjects receiving ZDV, men were
four times more likely to progress to a study endpoint than women. CONCLUSIONS:
Differences in pretreatment characteristics and on study experiences were
demonstrated between women and men enrolled in this clinical trial. The
suggestion of a gender difference in response to ZDV monotherapy by
antiretroviral-naive study subjects and the lower baseline values for HIV RNA in
women compared with those in men provides evidence for gender differences in the
relationship between virus replication, CD4+ decline, and responses to nucleoside
analogue therapy.
PMID- 11015148
TI - Effects of lipolysis or heat treatment on HIV-1 provirus in breast milk.
AB - BACKGROUND: Transmission of HIV-1 infection through breastfeeding is associated
with integrated DNA (provirus) in milk cells. Reduction of HIV-1 DNA in milk may
lessen infectivity. PURPOSE: To investigate efficacy of two methods available in
developing countries to reduce HIV-1 proviral DNA in breast milk. METHODS:
Methods simulated field conditions; milk was heated by bringing it to a boil, for
instance, over a cooking fire, and lipolysis was done at room temperature. Four
HIV-positive pregnant women were recruited for this pilot study, instructed to
feed formula exclusively, and to stimulate milk production using pumping. Milk
was collected twice weekly for 3 weeks and analyzed qualitatively for HIV-1
proviral DNA by polymerase chain reaction at three stages: 1) fresh, 2) after
standing for 6 hours, and 3) after having been brought to the boiling point.
RESULTS: Seventeen samples from 4 mothers were analyzed. Fifteen of 17 fresh
samples (88%) had measurable HIV-1 proviral DNA despite all mothers' having had
low or undetectable plasma viral loads. Lipolysis (standing at room temperature)
for 6 hours did not destroy proviral DNA: 6 of 7 samples (86%) tested positive
for DNA after lipolysis. No samples of milk (n = 8) brought to a boil were
positive for HIV-1 proviral DNA (p <.0001). CONCLUSIONS: This preliminary
evidence suggests that inherent lipolytic activity of fresh breast milk is
inadequate for destruction of HIV-1; bringing breast milk to a boil may result in
decreased HIV-1 infectivity; and breast milk cell-associated HIV-1 may not
reflect plasma viral load. Nutritional value or possible bacterial contamination
of milk treated in this manner was not assessed.
PMID- 11015149
TI - Cell-free virus in breast milk of HIV-1-seropositive women.
AB - To examine the prevalence, quantification, and factors that influence HIV in the
cell-free compartment of breast milk, we performed reverse transcription
polymerase chain reaction (RT-PCR) on samples obtained from HIV-1-infected study
subjects. Virus was detected in 86 of 136 samples (63.2%) from 79 study subjects.
HIV RNA quantity ranged from undetectable to 227,586 copies/ml. Prevalence and
mean viral load were not affected by postnatal ages or maternal vitamin A
supplementation. Among study subjects with multiple samples, breast milk viral
load did not change at different postnatal ages. Breast milk viral load
correlated positively with plasma viral load (r = 0.47; p =.005) and negatively
with maternal CD4 count at entry to the study (r = -0.26; p =.02). Mothers of HIV
infected children had a higher proportion of detectable HIV RNA in their breast
milk than mothers of uninfected children (p =.03) and higher mean log10 HIV RNA
quantities (p =.04). In a multivariate logistic regression model, log10 HIV RNA
quantity in breast milk was significantly associated with the risk of mother
child transmission (odds ratio [OR], 2.82; 95% confidence interval [CI], 1.22
6.51). Thus, prevention and treatment of opportunistic infections and of mastitis
and early weaning may be important elements of a public health policy that is
relevant to women in developing countries with HIV infection. Where available,
antiretrovirals may also have an impact on opportunistic infections and mastitis.
PMID- 11015150
TI - Reduced toxicity with gradual initiation of trimethoprim-sulfamethoxazole as
primary prophylaxis for Pneumocystis carinii pneumonia: AIDS Clinical Trials
Group 268.
AB - Trimethoprim-sulfamethoxazole (TMP/SMX) is recognized as the superior agent for
Pneumocystis carinii pneumonia (PCP) prophylaxis but a high incidence of adverse
drug reactions, which may be due to toxic drug metabolites, limits its use. AIDS
Clinical Trials Group protocol 268 was a randomized, double-blind, controlled two
arm trial designed to determine whether gradual initiation of TMP/SMX suspension
reduced the incidence of treatment-limiting adverse drug reactions compared with
routine initiation of double-strength (DS; 160 mg/800 mg) tablets. In all, 372
HIV-1-infected study subjects with a CD4+ cell count <250 x 10 cells/mm3 who had
not previously received TMP/SMX for PCP prophylaxis were randomized to receive
either daily TMP/SMX DS tablets or a gradually increasing dose of TMP/SMX
suspension. The suspension dose was increased to reach the equivalent of a DS
tablet by study day 13. During the first 2 weeks, study subjects also received a
matching placebo tablet/suspension. After week 2, all study subjects received
TMP/SMX tablets for the next 10 weeks. There were significantly fewer study
subjects who discontinued prophylaxis during the first 12 weeks when TMP/SMX
therapy was initiated gradually (17%) than when initiated in DS tablet
formulation (33%) (p =.0002). Gradual initiation was also associated with
significantly fewer adverse drug reactions. Gradual initiation of TMP/SMX for
primary PCP prophylaxis reduces the incidence of its treatment-limiting adverse
effects.
PMID- 11015151
TI - Oral ganciclovir systemic exposure is enhanced in HIV-infected patients with
diarrhea and weight loss.
AB - OBJECTIVE: To determine whether diarrhea and intestinal malabsorption during HIV
infection alter oral ganciclovir systemic exposure. METHODS: We studied the oral
disposition of ganciclovir in 42 HIV-infected patients stratified into three
groups: A (n = 15), HIV (stage A and B); B (n = 13), AIDS (stage C); and C (n =
14), AIDS with chronic diarrhea and wasting syndrome (10% or more weight loss).
Each patient was evaluated for nutritional (body mass index, serum albumin and
transferrin), immunologic (CD4 count, plasma viral load) and intestinal status (D
xylose test, fecal fat and nitrogen excretion, and intestinal permeability).
Following an overnight fast, 1 g oral ganciclovir was given to patients. Six
blood samples were collected over 24 hours. Serum was analyzed for ganciclovir by
high performance liquid chromatography. Drug disposition was characterized using
a population pharmacokinetic approach. RESULTS: Mean intestinal permeability
increased as HIV disease progressed (0. 05, 0.1, and 0.2 for groups A, B, and C,
respectively). Average weight-adjusted maximum concentration (Cmax) in group C
was twofold more than that in group A and B patients (12.5 versus 6 and 6.4
ng/ml/kg), and average area under the curve (AUC0-infinity) was threefold greater
in group C patients (193 versus 59 and 65 ng. hour/ml/kg in groups A and B,
respectively). Mean oral clearance was threefold lower in group C (96 versus 258
and 212 L/hour in groups A and B, respectively). CONCLUSION: Because systemic
exposure of oral ganciclovir is enhanced in AIDS patients with diarrhea and
wasting syndrome, oral ganciclovir therapy may benefit these patients.
PMID- 11015152
TI - Model of HIV-1 disease progression based on virus-induced lymph node homing and
homing-induced apoptosis of CD4+ lymphocytes.
AB - Several proposed theories have described the progression of HIV infection. Even
so, no concrete evidence supports any as comprehensive, including, for example,
why the CD4+ T-cell counts fall from 1000/mm3 of blood to roughly 100/mm3 over an
average 10-year period, whereas concomitant viral loads are relatively constant,
increasing by several orders of magnitude in late-stage disease. Here, we develop
and validate a theoretical model that altered lymphocyte circulation patterns
between the lymph system and blood due to HIV-induced enhanced lymph-node homing
and subsequent apoptosis of resting CD4+ T cells can explain many aspects of HIV
1 disease progression. These results lead to a recalculation of the CD4+
lymphocyte dynamics during highly active antiretroviral therapy, and also suggest
new targets for therapy.
PMID- 11015153
TI - Obtaining HIV test results with a home collection test kit in a community
telephone sample.
AB - OBJECTIVES: To test the feasibility of obtaining HIV test results by home
collection kit from a probability telephone sample of men who have sex with men
(MSM). METHODS: A quota sample of 615 MSM previously interviewed by the Urban
Men's Health Study phone survey in Chicago, Los Angeles, New York City, and San
Francisco were re-contacted and offered an HIV test using an oral specimen
(Orasure) home collection kit. RESULTS: Eighty percent consented to be mailed a
kit, and 84% returned a specimen, for a 67% participation rate. All self-reported
HIV-positive persons tested positive (77 of 77); 4 of 266 (1.5%) with a prior
negative test and 2 of 69 (2.9%) with no prior positive HIV test result.
Participation was associated with self-reported prior HIV test status-HIV
positive (83%), HIV-negative (68%), or no prior HIV test result (54%)-and
marginally associated with New York City residence after adjustment for HIV
status (odds ratio = 0.7; 95% confidence interval, 0.4-1.1; p =.08). CONCLUSIONS:
These results suggest that urban MSM identified and interviewed by telephone will
participate in home collection HIV testing. This methodology could be used to
produce population-based estimates of HIV seroprevalence and seroincidence in MSM
and could probably be extended to other populations and other viral infections.
PMID- 11015155
TI - Clinical spectrum, morbidity, and mortality of acquired immunodeficiency syndrome
in Taiwan: a 5-year prospective study.
AB - The clinical spectrum of AIDS and changes of morbidity and mortality associated
with HIV infection following initiation of highly active antiretroviral therapy
(HAART) are rarely described in the less developed countries in the Asia-Pacific
region. We prospectively observed on a follow-up basis 309 HIV-infected patients
(82.8% with AIDS) at National Taiwan University Hospital in Taiwan, where highly
active antiretroviral therapy (HAART) has been provided to all patients at no
charge at any stage of HIV infection since April 1, 1997, to describe the
spectrum of HIV-associated opportunistic diseases and evaluate changes of
morbidity and mortality from June 24, 1994 through June 23, 1999. Of the
patients, 59.3% at study entry had a CD4+ lymphocyte count of <50
cells/microliter. The five leading HIV-associated opportunistic infections
included oroesophageal candidiasis (195 patients), Pneumocystis carinii pneumonia
(93), tuberculosis (77), mucocutaneous herpes simplex infection (74), and
cytomegalovirus diseases (73). The incidence rates of seven major AIDS-defining
opportunistic diseases were declining though the changes of the relative
proportions varied. The median duration of hospitalization decreased from 36 days
in 1995 to 12 days in 1999 (p =.0001). Overestimated mortality rate declined from
148.4 per 100 patient-years in 1995 to 7.4 per 100 patient-years in 1999 (p
=.0001) whereas the underestimated mortality rate declined from 110.5 to 5.39 per
100 patient-years (p =.0001). Risk ratio (RR) for mortality in patients who
received HAART compared with those who did not was 0.410 (95% confidence interval
[CI], 0.249-0.674; p =.0004) and the RR was 0.250 (95% CI, 0.127-0.492; p =.0001)
when the analysis was limited to patients with an initial CD4+ lymphocyte count
<100 cells/microliter and follow-up duration >30 days after adjusting for their
age, gender, type of risk behavior, and CD4+ lymphocyte count. Morbidity and
mortality were declining with each study year even in a population consisting
mainly of patients at the advanced stage of HIV infection in Taiwan. Earlier
diagnosis, accumulation of clinical experience, and use of HAART were associated
with lower mortality rates.
PMID- 11015154
TI - Cost-effective use of nevirapine to prevent vertical HIV transmission in sub
Saharan Africa.
AB - OBJECTIVE: To assess the cost-effectiveness of alternative strategies of
nevirapine (NVP) administration to prevent vertical HIV transmission in sub
Saharan Africa. DESIGN: A decision-analysis model was constructed to estimate the
costs and effects of NVP-based prevention strategies for two separate groups of
women: those who qualify for standard therapy by attending a 36-week prenatal
visit, and those who do not qualify, owing to preterm delivery or lack of
prenatal care. RESULTS: For women in prenatal care, mass provision of NVP without
maternal serodiagnosis was found to yield greater health gains at an acceptable
cost, compared with providing targeted therapy to only those women identified as
seropositive. However, this conclusion was strongly contingent on several
uncertain assumptions, most importantly the probability that a woman who does not
know her serostatus will nonetheless adhere to therapy. Among those women who
present for delivery without prior enrollment in a prenatal strategy, either late
provision of maternal-infant NVP or treatment of only the infant would likely be
a cost-effective alternative to the current practice of offering no preventive
therapy. CONCLUSIONS: NVP intervention offers a cost-effective avenue for
preventing vertical HIV transmission in sub-Saharan Africa. The optimal choice
between mass therapy and targeted therapy cannot be confidently identified
without information regarding adherence among women who do not know their
serostatus. For women who do not receive NVP prenatally, treatment on
presentation for delivery would be cost-effective even in the face of modest
clinical efficacy. Clinical assessment of adherence to therapy among women who do
not know their status and the field effectiveness of alternative approaches to
NVP administration is urgently needed to allow identification of optimal
prevention strategies.
PMID- 11015156
TI - High-risk behaviors during incarceration in African-American men treated for HIV
at three Los Angeles public medical centers.
AB - OBJECTIVES: This paper describes research that examined the association between
high-risk sexual and drug-using behaviors during incarceration and HIV infection
for African-American men receiving HIV care at three public medical centers in
Los Angeles County (LAC), California. METHODS: A case-control study was conducted
in which 305 HIV-infected African-American men and 305 neighborhood controls,
ages 20 to 49, were frequency-matched by age. RESULTS: After controlling for anal
sex while not incarcerated, we found no association between anal sex during
incarceration and HIV (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.6
2.2). Among men with a history of incarceration (n = 332), the percentage
reporting anal sex with men outside of incarceration (45%) was greater than those
reporting anal sex while incarcerated (16%). Injection drug use (IDU) during
incarceration was also not associated with HIV when controlling for IDU outside
of incarceration (OR, 1.6; 95% CI, 0.5- 4.9). Increased time in jail or prison
was associated with less HIV infection (p =.001). CONCLUSIONS: Although high-risk
behaviors are more common in the community than in the incarcerated setting for
this study group, incarcerated populations represent a high-risk group for whom
access to prevention messages is limited. Periods of incarceration represent a
unique opportunity to convey prevention messages that focus on high-risk
behaviors outside the incarcerated setting.
PMID- 11015157
TI - Anal sex among HIV-seronegative women at high risk of HIV exposure. The HIVNET
Vaccine Preparedness Study 2 Protocol Team.
AB - To assess the prevalence and the sociodemographic and behavioral correlates of
anal sex in a cohort of HIV-seronegative U.S. women at high risk of HIV exposure,
we administered a risk assessment using audio computer-assisted self-interview (A
CASI). Of 1268 sexually active women, 432 (32%) reported anal sex in the previous
6 months. Compared with women who did not report anal sex, those who did had more
unprotected vaginal sex (median of 11 versus 7 episodes; p <. 001) and a higher
proportion of unprotected sexual (vaginal plus anal) episodes (median of 0.90
versus 0.81; p =.01). Anal sex was reported by higher proportions of women who
did not always use condoms, who used crack in the past year, who were =35 years
of age, with no formal education beyond high school, who had had a diagnosed
sexually transmitted disease in the previous year, a primary male sex partner,
and a male sex partner with a history of injecting use. Women were more likely to
report anal sex by A-CASI than during interviewer-administered risk assessments
(odds ratio [OR], 9.00; 95% confidence interval [CI], 1.14-71.0). A less biased
method of ascertainment may account for the large proportion of women reporting
anal sex. Given increased vaginal risk among women reporting anal sex, the
relative importance of anal sex in heterosexual transmission merits further
study. Behavioral and biomedical prevention strategies effective for anal as well
as vaginal sex are needed.
PMID- 11015158
TI - Effects of CCR5 genetic polymorphism and HIV-1 subtype in antiretroviral response
in Brazilian HIV-1-infected patients.
PMID- 11015159
TI - Rivastigmine (Exelon) for Alzheimer's disease.
PMID- 11015160
TI - Zonisamide (Zonegran) for epilepsy.
PMID- 11015161
TI - Eflornithine cream for facial hair reduction.
PMID- 11015162
TI - Discontinuation of Mycobacterium avium complex prophylaxis in patients with
antiretroviral therapy-induced increases in CD4+ cell count. A randomized, double
blind, placebo-controlled trial. AIDS Clinical Trials Group 362 Study Team.
AB - BACKGROUND: Patients infected with HIV who experience increases in CD4(+) cell
counts are at reduced risk for opportunistic infections. However, the safety of
discontinuing prophylaxis against Mycobacterium avium complex has been uncertain.
OBJECTIVE: To compare the rate of M. avium complex infection in patients with
increased CD4(+) cell counts who receive azithromycin and those receiving
placebo. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 29
university-based clinical centers in the United States. PARTICIPANTS: 643 HIV-1
infected patients with a previous CD4(+) cell count less than 0.05 x 10(9)
cells/L and a sustained increase to greater than 0.10 x 10(9) cells/L during
antiretroviral therapy. INTERVENTION: Azithromycin, 1200 mg once weekly (n =
321), or matching placebo (n = 322). MEASUREMENTS: Mycobacterium avium complex
cultures, CD4(+) cell counts, and clinical evaluations for AIDS-defining
illnesses and bacterial infections were done every 8 weeks. Plasma HIV-1 RNA
levels were measured at 16-week intervals. RESULTS: During follow-up (median, 16
months), 2 cases of M. avium complex infection were reported among the 321
patients assigned to placebo (incidence rate, 0.5 event per 100 person-years [95%
CI, 0.06 to 1.83 events per 100 person-years]) compared with no cases among the
322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person
years), resulting in a treatment difference of 0.5 event per 100 person-years
(CI, -0.20 to 1.21 events per 100 person-years) for placebo versus azithromycin.
Both cases were atypical in that M. avium complex was localized to the vertebral
spine. Patients receiving azithromycin were more likely than those receiving
placebo to discontinue treatment with the study drug permanently because of
adverse events (8% vs. 2%; hazard ratio, 0.24 [CI, 0.10 to 0.57]). CONCLUSIONS:
Prophylaxis against Mycobacterium avium complex can safely be withdrawn or
withheld in adults with HIV infection who experience increases in CD4(+) cell
count while receiving antiretroviral therapy.
PMID- 11015163
TI - High-dose chemotherapy and autologous stem-cell transplantation for ovarian
cancer: an autologous blood and marrow transplant registry report.
AB - BACKGROUND: Autologous transplantation is increasingly used to treat epithelial
ovarian cancer. However, it is not clear which patients may benefit. OBJECTIVE:
To determine overall and progression-free survival and factors associated with
favorable outcome after autotransplantation for ovarian cancer. DESIGN:
Observational cohort study. SETTING: 57 centers reporting to the Autologous Blood
and Marrow Transplant Registry (ABMTR). PATIENTS: 421 women who received
transplants between 1989 and 1996. INTERVENTIONS: High-dose chemotherapy using
diverse regimens with hematopoietic stem-cell rescue. MEASUREMENTS: Primary
outcomes were progression-free survival and overall survival. Multivariate
analyses using Cox proportional hazards regression considered the following
factors: age, Karnofsky performance score, initial stage, histologic
characteristics, previous therapy, remission status, extent of disease, graft
source, transplant regimen, and year of transplantation. RESULTS: Most patients
had extensive previous chemotherapy. Forty-one percent had platinum-resistant
tumors, and 38% had tumors at least 1 cm in diameter. Only 34 patients (8%)
received transplants as part of initial therapy. The probability of death within
100 days was 11% (95% CI, 8% to 14%). Two-year progression-free survival was 12%
(CI, 9% to 16%), and 2-year overall survival was 35% (CI, 30% to 41%). Younger
age, Karnofsky performance score of at least 90%, non-clear-cell disease,
remission at transplantation, and platinum sensitivity were associated with
better outcomes. Progression-free and overall survival were 22% (CI, 12% to 33%)
and 55% (CI, 42% to 66%), respectively, for women with a high Karnofsky
performance score and non-clear-cell, platinum-sensitive tumors. CONCLUSIONS:
Some subgroups of patients with ovarian cancer seem to have good outcomes after
autotransplantation, although several biases may have affected these
observations. Phase III trials are needed to compare such outcomes with outcomes
of conventional chemotherapy.
PMID- 11015164
TI - Low-dose hydrochlorothiazide and preservation of bone mineral density in older
adults. A randomized, double-blind, placebo-controlled trial.
AB - BACKGROUND: Thiazide may have beneficial effects on bone mineral density and may
reduce risk for hip fracture. However, the existence of a causal role remains
uncertain because experimental evidence is limited. OBJECTIVE: To determine the
effect of hydrochlorothiazide on rates of bone loss in older adults. DESIGN:
Randomized, double-blind, placebo-controlled trial with 3-year follow-up.
SETTING: A large health maintenance organization in western Washington State.
PARTICIPANTS: 320 healthy, normotensive adults (205 women, 115 men) 60 to 79
years of age. INTERVENTION: Random assignment to one of three study groups: 12.5
mg of hydrochlorothiazide per day, 25 mg of hydrochlorothiazide per day, or
placebo. MEASUREMENTS: Bone mineral density using dual-energy x-ray
absorptiometry at the total hip, posterior-anterior spine, and total body; blood
and urine markers of bone metabolism; incident falls, clinical fractures, and
radiographic vertebral fractures. RESULTS: 309 of 320 participants completed the
36-month visit (97%). Adherence to study medication throughout follow-up was high
in all participants (81.6% to 89.7%) except men in the high-dose
hydrochlorothiazide group (60.5%). According to intention-to-treat analysis, the
36-month differences in percentage change in total hip bone mineral density were
0.79 percentage point (95% CI, -0.12 to 1.71) for the 12.5-mg hydrochlorothiazide
group and 0.92 percentage point (CI, -0.001 to 1.85) for the 25-mg group compared
with placebo (P = 0.03). Percentage change at the posterior-anterior spine was
significantly greater for the 25-mg hydrochlorothiazide group at 6 months
(intergroup difference, 1.04 percentage points [CI, 0.22 to 1.86]) compared with
placebo (P = 0.005); at 36 months, this difference was 0.82 percentage point (CI,
-0.36 to 2.01; P = 0.12). No significant differences were seen in total-body bone
mineral density between the treatment groups. Treatment effects were stronger in
women than in men. CONCLUSIONS: In healthy older adults, low-dose
hydrochlorothiazide preserves bone mineral density at the hip and spine. The
modest effects observed over 3 years, if accumulated over 10 to 20 years, may
explain the one-third reduction in risk for hip fracture associated with thiazide
in many epidemiologic studies.
PMID- 11015165
TI - Attitudes and practices of U.S. oncologists regarding euthanasia and physician
assisted suicide.
AB - BACKGROUND: The practices of euthanasia and physician-assisted suicide remain
controversial. OBJECTIVE: To achieve better understanding of attitudes and
practices regarding euthanasia and physician-assisted suicide in the context of
end-of-life care. DESIGN: Cohort study. SETTING: United States. PARTICIPANTS:
3299 oncologists who are members of the American Society of Clinical Oncology.
MEASUREMENTS: Responses to survey questions on attitudes toward euthanasia and
physician-assisted suicide for a terminally ill patient with prostate cancer who
has unremitting pain, requests for and performance of euthanasia and physician
assisted suicide, and sociodemographic characteristics. RESULTS: Of U.S.
oncologists surveyed, 22.5% supported the use of physician-assisted suicide for a
terminally ill patient with unremitting pain and 6.5% supported euthanasia.
Oncologists who were reluctant to increase the dose of intravenous morphine for
terminally ill patients in excruciating pain (odds ratio [OR], 0.61 [95% CI, 0.48
to 0.77]) and had sufficient time to talk to dying patients about end-of-life
care issues (OR, 0.79 [CI, 0.71 to 0.87]) were less likely to support euthanasia
or physician-assisted suicide. During their career, 3.7% of surveyed oncologists
had performed euthanasia and 10.8% had performed physician-assisted suicide.
Oncologists who were reluctant to increase the morphine dose for patients in
excruciating pain (OR, 0.58 [CI, 0.43 to 0.79]) and those who believed that they
had received adequate training in end-of-life care (OR, 0.86 [CI, 0.79 to 0.95])
were less likely to have performed euthanasia or physician-assisted suicide.
Oncologists who reported not being able to obtain all the care that a dying
patient needed were more likely to have performed euthanasia (P = 0.001).
CONCLUSIONS: Requests for euthanasia and physician-assisted suicide are likely to
decrease as training in end-of-life care improves and the ability of physicians
to provide this care to their patients is enhanced.
PMID- 11015166
TI - Upright posture and postprandial hypotension in elderly persons.
AB - BACKGROUND: Syncope and falls are common in elderly persons and often result from
the interaction of multiple clinical abnormalities. Both orthostatic hypotension
and postprandial hypotension increase in prevalence with age. OBJECTIVE: To
determine whether meal ingestion enhances orthostatic hypotension in elderly
persons. DESIGN: Controlled paired comparison. SETTING: Clinical research center.
PATIENTS: 50 functionally independent elderly persons recruited from local senior
centers (n = 47) and from patients hospitalized with an unexplained fall or
syncope (n = 3) (mean age, 78 years [range, 61 to 96 years]). Twenty-five
participants (50%) were taking antihypertensive medication. MEASUREMENTS:
Sequential head-up tilt-table testing at 60 degrees was performed before and 30
minutes after ingestion of a standardized warm liquid meal that was high in
carbohydrates. Heart rate and blood pressure were continuously monitored.
RESULTS: Meal ingestion (P < 0.01) and time spent upright (P < 0.001) were
significantly associated with systolic blood pressure, but no significant
interaction was found between meal ingestion and time spent upright (P > 0.2).
These findings suggest that the association between meal ingestion and head-up
tilt-table testing were additive and not synergistic. However, the proportion of
participants with symptomatic hypotension increased during head-up tilt-table
testing after meal ingestion (12% during preprandial testing and 22% during
postprandial testing). Symptomatic hypotension tended to occur more often and
sooner after meal ingestion than before meal ingestion (P = 0.03). CONCLUSIONS:
Meal ingestion and head-up tilt-table testing are associated with increasing
occurrences of symptomatic hypotension. After meal ingestion and head-up tilt
table testing, 22% of functionally independent elderly persons had symptomatic
hypotension.
PMID- 11015167
TI - Diagnostic implications of elevated levels of smooth-muscle myosin heavy-chain
protein in acute aortic dissection. The smooth muscle myosin heavy chain study.
AB - BACKGROUND: A rapid 30-minute assay of circulating smooth-muscle myosin heavy
chain protein has been developed as a biochemical diagnostic tool for aortic
dissection. OBJECTIVE: To determine the sensitivity and specificity of this
assay. DESIGN: Cross-sectional study. SETTING: 8 major cardiovascular centers in
Japan. PATIENTS: 95 patients with acute aortic dissection, 48 patients with acute
myocardial infarction, and 131 healthy volunteers. MEASUREMENTS: Levels of
circulating smooth-muscle myosin heavy-chain protein. RESULTS: Patients with
acute aortic dissection who presented within 3 hours after onset had elevated
levels of circulating smooth-muscle myosin heavy-chain protein. In these
patients, the assay had a sensitivity of 90.9%, a specificity of 98% compared
with healthy volunteers, and a specificity of 83% compared with patients who had
acute myocardial infarction; the clinical decision limit was 2.5 microgram/L. All
patients with proximal lesions had elevated levels of smooth-muscle myosin heavy
chain protein, and only patients with distal lesions had decreased levels (<2.5
microgram/L). CONCLUSIONS: Levels of smooth-muscle myosin heavy-chain protein can
be used to diagnose aortic dissection soon after symptom onset. The assay had the
greatest diagnostic value in patients with proximal lesions.
PMID- 11015168
TI - Update in gastroenterology.
PMID- 11015169
TI - "The lower the better" in hypercholesterolemia therapy: a reliable clinical
guideline?.
AB - Since the publication of the second set of guidelines by the National Cholesterol
Education Program, a solid body of data from landmark clinical studies has
demonstrated that reduction in low-density lipoprotein (LDL) cholesterol with 3
hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ("statin") therapy
sharply diminishes the risk for coronary artery disease. These trials include the
Scandinavian Simvastatin Survival Study, the West of Scotland Coronary Prevention
Study, the Air Force/Texas Coronary Atherosclerosis Prevention Study, the
Cholesterol and Recurrent Events investigation, and the Long-Term Intervention
with Pravastatin in Ischaemic Disease trial. Coronary event rates and, in some
cases, all-cause mortality decreased significantly after about 5 years of statin
therapy in patients at risk for and those who had coronary artery disease at
baseline. In contrast, recent subgroup analyses of these pivotal studies have in
the aggregate challenged the premise that lower LDL cholesterol levels
necessarily lead to further declines in risk for coronary artery disease,
particularly among the patients most likely to be seen by the clinician: those
with moderately elevated or normal cholesterol profiles. Indeed, when LDL
cholesterol levels are in this range, further lowering with statin therapy
elicits diminishing returns in terms of coronary event rates. These findings are
readily accommodated by the curvilinear, or log-linear, model between serum
cholesterol level and risk for coronary artery disease, which is predicated on
data from large epidemiologic studies. In light of the current climate involving
competing health care costs, the pursuit of progressively diminishing returns in
terms of reductions in coronary artery disease risk through more aggressive
lowering of LDL cholesterol levels appears to be unwarranted. Until data are
published from ongoing randomized, clinical trials that can more effectively
resolve the clinical utility of aggressive lipid-lowering strategies to improve
coronary event rates, a prudent, evidence-based strategy seems warranted.
PMID- 11015170
TI - Autologous stem-cell transplantation in ovarian cancer: is more better?
PMID- 11015171
TI - The Face of Evil.
PMID- 11015172
TI - On being a doctor. Alternative healer.
PMID- 11015173
TI - Responding to intractable terminal suffering.
PMID- 11015174
TI - Responding to intractable terminal suffering.
PMID- 11015175
TI - Responding to intractable terminal suffering.
PMID- 11015176
TI - Responding to Intractable Terminal Suffering.
PMID- 11015177
TI - Palliative treatment of last resort and assisted suicide.
PMID- 11015178
TI - Palliative Treatment of Last Resort and Assisted Suicide.
PMID- 11015180
TI - Palliative Treatment of Last Resort and Assisted Suicide.
PMID- 11015179
TI - Palliative treatment of last resort and assisted suicide.
PMID- 11015181
TI - Publication of papers on assisted suicide and terminal sedation.
PMID- 11015182
TI - Publication of Papers on Assisted Suicide and Terminal Sedation.
PMID- 11015184
TI - Medicine and the Movies: Lorenzo's Oil at Century's End.
PMID- 11015183
TI - Publication of Papers on Assisted Suicide and Terminal Sedation.
PMID- 11015185
TI - Parting Company: Understanding the Loss of a Loved One. The Caregiver's Journey.
PMID- 11015186
TI - Transfusion Therapy: Clinical Principles and Practice.
PMID- 11015187
TI - Mechanism of transmembrane signaling: insulin binding and the insulin receptor.
AB - Transmembrane signaling via receptor tyrosine kinases generally requires
oligomerization of receptor monomers, with the formation of ligand-induced dimers
or higher multimers of the extracellular domains of the receptors. Such
formations are expected to juxtapose the intracellular kinase domains at the
correct distances and orientations for transphosphorylation. For receptors of the
insulin receptor family that are constitutively dimeric, or those that form
noncovalent dimers without ligands, the mechanism must be more complex. For
these, the conformation must be changed by the ligand from one that prevents
activation to one that is permissive for kinase phosphorylation. How the insulin
ligand accomplishes this action has remained a puzzle since the discovery of the
insulin receptor over 2 decades ago, primarily because membrane proteins in
general have been refractory to structure determination by crystallography.
However, high-resolution structural evidence on individual separate subdomains of
the insulin receptor and of analogous proteins has been obtained. The recently
solved quaternary structure of the complete dimeric insulin receptor in the
presence of insulin has now served as the structural envelope into which such
individual domains were fitted. The combined structure has provided answers on
the details of insulin/receptor interactions in the binding site and on the
mechanism of transmembrane signaling of this covalent dimer. The structure
explains many observations on the behavior of the receptor, from greater or
lesser binding of insulin and its variants, point and deletion mutants of the
receptor, to antibody-binding patterns, and to the effects on basal and insulin
stimulated autophosphorylation under mild reducing conditions.
PMID- 11015188
TI - Metal-phosphate interactions in the hammerhead ribozyme observed by 31P NMR and
phosphorothioate substitutions.
AB - The hammerhead ribozyme is a catalytic RNA that requires divalent metal cations
for activity under moderate ionic strength. Two important sites that are proposed
to bind metal ions in the hammerhead ribozyme are the A9/G10.1 site, located at
the junction between stem II and the conserved core, and the scissile phosphate
(P1.1). (31)P NMR spectroscopy in conjunction with phosphorothioate substitutions
is used in this study to investigate these putative metal sites. The (31)P NMR
feature of a phosphorothioate appears in a unique spectral window and can be
monitored for changes upon addition of metals. Addition of 1-2 equiv of Cd(2+) to
the hammerhead with an A9-S(Rp) or A9-S(S)(Rp) substitution results in a 2-3 ppm
upfield shift of the (31)P NMR resonance. In contrast, the P1.1-S(Rp) and P1.1
S(Sp) (31)P NMR features shift slightly and in opposite directions, with a total
change in delta of =0.6 ppm with addition of up to 10 equiv of Cd(2+). No
significant shifts are observed for an RNA.RNA duplex with a single, internal
phosphorothioate modification upon addition of Cd(2+). Data obtained using model
compounds including diethyl phosphate/thiophosphate, AMP, and AMPS, show that a
Cd(2+)-S interaction yields an upfield shift for the (31)P NMR resonance, even in
the case of a weak coordination such as with diethyl thiophosphate. Taken
together, these data predict that Cd(2+) has a high affinity for the A9 site and
suggest that there is flexibility in metal coordination within the binding
pocket. Cd(2+) interactions with the cleavage site P1.1-S positions are weaker
and appear to be stereospecific. These data have implications for mechanisms that
have been proposed to explain the influence of metal ions on hammerhead ribozyme
activity. These experiments also show the potential utility of (31)P NMR
spectroscopy in conjunction with phosphorothioates as a probe for metal binding
sites in nucleic acids.
PMID- 11015189
TI - The curvature of dA tracts is temperature dependent.
AB - The curvature of dA tracts has been proposed to be important in the recognition,
packaging, and regulation of DNA. The effects of dA tracts on the gel mobility,
rate of cyclization, and other properties of DNA have been extensively studied.
The consensus value for the curvature induced by a single dA tract is about 18
degrees. There are two main competing models for the origin of the curvature of
dA tracts. One model assigns the central role to sequence-dependent steric
clashes and the other to sequence dependent interactions with cations. The
temperature dependence of the shape functions, the molecule specific part of the
diffusion coefficients, of a set of six DNAs has been examined here. The set
contains DNAs with dA tracts in or out of phase with respect to the helical
repeat as well as those with scrambled dA-dT regions. The results show that the
curvature of dA tracts is highly temperature dependent and that the curvature is
largely melted out by 40 degrees C. The curvature melts out before there is
significant premelting, or breathing of the dA tracts or the scrambled dA-dT
regions. The curvature does not appear to reach a plateau value at low
temperatures. A qualitative model for the melting of the curvature of dA tracts
is proposed.
PMID- 11015190
TI - The active site structure of Thalassiosira weissflogii carbonic anhydrase 1.
AB - X-ray absorption spectroscopy at the Zn K-edge indicates that the active site of
the marine diatom Thalassiosira weissflogii carbonic anhydrase is strikingly
similar to that of mammalian alpha-carbonic anhydrase enzymes. The zinc has three
histidine ligands and a single water at 1.98 A. This is quite different from the
beta-carbonic anhydrases of higher plants in which zinc is coordinated by two
cysteine thiolates, one histidine, and a water molecule. The diatom carbonic
anhydrase shows no significant sequence similarity with other carbonic anhydrases
and may represent an example of convergent evolution at the molecular level.
PMID- 11015191
TI - Folded state of the integral membrane colicin E1 immunity protein in solvents of
mixed polarity.
AB - The colicin E1 immunity protein (ImmE1), a 13.2-kDa hydrophobic integral membrane
protein localized in the Escherichia coli cytoplasmic membrane, protects the cell
from the lethal, channel-forming activity of the bacteriocin, colicin E1.
Utilizing its solubility in organic solvents, ImmE1 was purified by 1-butanol
extraction of isolated membranes, followed by gel filtration and ion-exchange
chromatography in a chloroform/methanol/H(2)O (4:4:1) solvent system. Circular
dichroism analysis indicated that the alpha-helical content of ImmE1 is
approximately 80% in 1-butanol or 2,2,2-trifluoroethanol, consistent with a
previous membrane-folding model with three extended hydrophobic transmembrane
helical domains, H1-H3. Each of these extended hydrophobic domains contains a
centrally located single Cys residue that could be used as a probe of protein
structure. The presence of tertiary structure of purified ImmE1 in a solvent of
mixed polarity, chloroform/methanol/H(2)O (4:4:1) was demonstrated by (i) the
constraints on Tyr residues shown by the amplitude of near-UV circular dichroism
spectra in the wavelength interval, 270-285 nm; (ii) the correlation between the
near-UV Tyr CD spectrum of single and double Cys-to-X mutants of the Imm protein
and their in vivo activity; (iii) the upfield shift of methyl groups in a 1D NMR
spectrum, a 2D- HSQC NMR spectrum of ImmE1 in the mixed polarity solvent mixture,
and a broadening and disappearance of the indole (1)H proton resonance from Trp94
in H3 by a spin label attached to Cys16 in the H2 hydrophobic domain; (iv) near
UV circular dichroism spectra with a prominent ellipticity band centered at 290
nm from a single Trp inserted into the extended hydrophobic domains. It was
concluded that the colicin E1 immunity protein adopts a folded conformation in
chloroform/methanol/H(2)O (4:4:1) that is stabilized by helix-helix interactions.
Analysis of the probable membrane folding topology indicated that several Tyr
residues in the bilayer region of the three transmembrane helices could
contribute to the near-UV CD spectrum through helix-helix interactions.
PMID- 11015192
TI - Functional implications of disulfide bond, Cys206-Cys210, in recombinant
prochymosin (chymosin).
AB - Prochymosin (chymosin) contains three disulfide bonds: Cys45-Cys50, Cys206
Cys210, and Cys250-Cys283. We have demonstrated that Cys250-Cys283 is
indispensable for correct refolding of prochymosin, whereas Cys45-Cys50 is
dispensable but has some contribution to the stability and substrate specificity
of the enzyme. Here, we report the results about the functions of Cys206-Cys210
by site-directed mutagenesis studies. In a glutathione redox system C206A/C210A
mutant exhibited oxidative refolding kinetics and efficiency ( approximately 40%
reactivation) similar to those of the wild-type prochymosin, indicating that
Cys206-Cys210 is also dispensable for refolding. However, C206S/C210S and single
site mutants (C210A, C210S, and C206A) showed only about 3 and 0-0.4%
reactivation, respectively. This is quite different from the Cys45-Cys50
deficient mutants (C45A, C50A, C45A/C50A, C45D, C50S, C45D/C50S, C45A/C50S),
which have comparable refolding efficiencies, implying that the substituents at
position 206 and 210 play more important role in determining correct refolding
than those at position 45 and 50. Urea-induced denaturation and fluorescence
quenching studies indicated that the prochymosin mutants C206A/C210A and
C206S/C210S were 2.1 and 4.8 kJ/mol less stable than prochymosin and some
tryptophan residue in the mutated molecules was less exposed. However, the wild
type and mutant prochymosins shared similar far-UV CD and fluorescence emission
spectra and similar specific potential activity, suggesting that the overall
conformation was maintained after mutation. Activity assay and kinetic analysis
revealed that mutation did not change the specific milk-clotting activity
significantly but resulted in an increase in K(m) and k(cat) toward a hexapeptide
substrate. On the basis of the above-mentioned perturbance of tryptophanyl
microenvironment and the three-dimensional structure of chymosin, we proposed
that deletion of Cys206-Cys210 may induce a propagated conformational change,
resulting in a perturbance of the local conformation around active-site cleft and
in turn, an alteration of the substrate specificity.
PMID- 11015193
TI - Structure and calcium-binding properties of Frq1, a novel calcium sensor in the
yeast Saccharomyces cerevisiae.
AB - The FRQ1 gene is essential for growth of budding yeast and encodes a 190-residue,
N-myristoylated (myr) calcium-binding protein. Frq1 belongs to the
recoverin/frequenin branch of the EF-hand superfamily and regulates a yeast
phosphatidylinositol 4-kinase isoform. Conformational changes in Frq1 due to N
myristoylation and Ca(2+) binding were assessed by nuclear magnetic resonance
(NMR), fluorescence, and equilibrium Ca(2+)-binding measurements. For this
purpose, Frq1 and myr-Frq1 were expressed in and purified from Escherichia coli.
At saturation, Frq1 bound three Ca(2+) ions at independent sites, which
correspond to the second, third, and fourth EF-hand motifs in the protein.
Affinity of the second site (K(d) = 10 microM) was much weaker than that of the
third and fourth sites (K(d) = 0.4 microM). Myr-Frq1 bound Ca(2+) with a K(d)app
of 3 microM and a positive Hill coefficient (n = 1.25), suggesting that the N
myristoyl group confers some degree of cooperativity in Ca(2+) binding, as seen
previously in recoverin. Both the NMR and fluorescence spectra of Frq1 exhibited
very large Ca(2+)-dependent differences, indicating major conformational changes
induced upon Ca(2+) binding. Nearly complete sequence-specific NMR assignments
were obtained for the entire carboxy-terminal domain (residues K100-I190).
Assignments were made for 20% of the residues in the amino-terminal domain;
unassigned residues exhibited very broad NMR signals, most likely due to Frq1
dimerization. NMR chemical shifts and nuclear Overhauser effect (NOE) patterns of
Ca(2+)-bound Frq1 were very similar to those of Ca(2+)-bound recoverin,
suggesting that the overall structure of Frq1 resembles that of recoverin. A
model of the three-dimensional structure of Ca(2+)-bound Frq1 is presented based
on the NMR data and homology to recoverin. N-myristoylation of Frq1 had little or
no effect on its NMR and fluorescence spectra, suggesting that the myristoyl
moiety does not significantly alter Frq1 structure. Correspondingly, the NMR
chemical shifts for the myristoyl group in both Ca(2+)-free and Ca(2+)-bound myr
Frq1 were nearly identical to those of free myristate in solution, indicating
that the fatty acyl chain is solvent-exposed and not sequestered within the
hydrophobic core of the protein, unlike the myristoyl group in Ca(2+)-free
recoverin. Subcellular fractionation experiments showed that both the N-myristoyl
group and Ca(2+)-binding contribute to the ability of Frq1 to associate with
membranes.
PMID- 11015194
TI - Molecular modeling, affinity labeling, and site-directed mutagenesis define the
key points of interaction between the ligand-binding domain of the vitamin D
nuclear receptor and 1 alpha,25-dihydroxyvitamin D3.
AB - We have combined molecular modeling and classical structure-function techniques
to define the interactions between the ligand-binding domain (LBD) of the vitamin
D nuclear receptor (VDR) and its natural ligand, 1alpha,25-dihydroxyvitamin D(3)
[1alpha,25-(OH)(2)D(3)]. The affinity analogue 1alpha,25-(OH)(2)D(3)-3
bromoacetate exclusively labeled Cys-288 in the VDR-LBD. Mutation of C288 to
glycine abolished this affinity labeling, whereas the VDR-LBD mutants C337G and
C369G (other conserved cysteines in the VDR-LBD) were labeled similarly to the
wild-type protein. These results revealed that the A-ring 3-OH group docks next
to C288 in the binding pocket. We further mutated M284 and W286 (separately
creating M284A, M284S, W286A, and W286F) and caused severe loss of ligand
binding, indicating the crucial role played by the contiguous segment between
M284 and C288. Alignment of the VDR-LBD sequence with the sequences of nuclear
receptor LBDs of known 3-D structure positioned M284 and W286 in the presumed
beta-hairpin of the molecule, thereby identifying it as the region contacting the
A-ring of 1alpha, 25-(OH)(2)D(3). From the multiple sequence alignment, we
developed a homologous extension model of the VDR-LBD. The model has a canonical
nuclear receptor fold with helices H1-H12 and a single beta hairpin but lacks the
long insert (residues 161-221) between H2 and H3. We docked the alpha
conformation of the A-ring into the binding pocket first so as to incorporate the
above-noted interacting residues. The model predicts hydrogen bonding contacts
between ligand and protein at S237 and D299 as well as at the site of the natural
mutation R274L. Mutation of S237 or D299 to alanine largely abolished ligand
binding, whereas changing K302, a nonligand-contacting residue, to alanine left
binding unaffected. In the "activation" helix 12, the model places V418 closest
to the ligand, and, consistent with this prediction, the mutation V418S abolished
ligand binding. The studies together have enabled us to identify 1alpha,25
(OH)(2)D(3)-binding motifs in the ligand-binding pocket of VDR.
PMID- 11015195
TI - Selective recognition of glutathiolated aldehydes by aldose reductase.
AB - In this study, the selectivity and specificity of aldose reductase (AR) for
glutathionyl aldehydes was examined. Relative to free aldehydes, AR was a more
efficient catalyst for the reduction of glutathiolated aldehydes. Reduction of
glutathionyl propanal [gammaGlu-Cys(propanal)-Gly] was more efficient than that
of Gly-Cys(propanal)-Gly and gamma-aminobutyric acid-Cys(propanal)-Gly suggesting
a possible interaction between alpha-carboxyl of the conjugate and AR. Two active
site residues, Trp20 or Ser302, were identified by molecular modeling as
potential sites of this interaction. Mutations containing tryptophan-to
phenylalanine (W20F) and serine-to-alanine (S302A) substitutions did not
significantly affect reduction of free aldehydes but decreased the catalytic
efficiency of AR for glutathiolated aldehydes. Combined mutations indicate that
both Trp20 and Ser302 are required for efficient catalysis of the conjugates. The
decrease in efficiency due to W20F mutation with glutathionyl propanal was not
observed with gamma-aminobutyric-Cys(propanal)-Gly or Gly-Cys-(propanal)-Gly,
indicating that Trp20 is involved in binding the alpha-carboxyl of the conjugate.
The effect of the S302A mutation was less severe when gammaGlu-Cys(propanal)-Glu
rather than glutathionyl propanal was used as the substrate, consistent with an
interaction between Ser302 and Gly-3 of the conjugate. These observations suggest
that glutathiolation facilitates aldehyde reduction by AR and enhances the range
of aldehydes available to the enzyme. Because the N-terminal carboxylate is
unique to glutathione, binding of the conjugate with the alpha-carboxyl facing
the bottom of the alpha/beta-barrel may assist in the exclusion of unrelated
peptides and proteins.
PMID- 11015196
TI - The competitive interaction of actin and PIP2 with actophorin is based on
overlapping target sites: design of a gain-of-function mutant.
AB - We studied the effect of mutations in an alpha-helical region of actophorin
(residues 91-108) on F-actin and PIP(2) binding. As in cofilin, residues in the
NH(2)-terminal half of this region are involved in F-actin binding. We show here
also that basic residues in the COOH-terminal half of the region participate in
this interaction whereby we extend the previously defined actin binding interface
[Lappalainen, P., et al. (1997) EMBO J. 16, 5520-5530]. In addition, we
demonstrate that some of the lysines in this alpha-helical region in actophorin
are implicated in PIP(2) binding. This indicates that the binding sites of F
actin and PIP(2) on actophorin overlap, explaining the mutually exclusive binding
of these ligands. The Ca(2+)-dependent F-actin binding of a number of actophorin
mutants (carrying a lysine to glutamic acid substitution at the COOH-terminal
positions of the actin binding helical region) may mimic the behavior of members
of the gelsolin family. In addition, we show that PIP(2) binding, but not actin
binding, of actophorin is strongly enhanced by a point mutation that leads to a
reinforcement of the positive electrostatic potential of the studied alpha
helical region.
PMID- 11015197
TI - The fourth transmembrane segment of the dopamine D2 receptor: accessibility in
the binding-site crevice and position in the transmembrane bundle.
AB - The binding site of the dopamine D2 receptor, like that of homologous G-protein
coupled receptors (GPCRs), is contained within a water-accessible crevice formed
among its seven transmembrane segments (TMSs). Using the substituted-cysteine
accessibility method (SCAM), we are mapping the residues that contribute to the
surface of this binding-site crevice. We have mutated to cysteine, one at a time,
21 consecutive residues in the fourth TMS (TM4). Eleven of these mutants reacted
with charged sulfhydryl-specific reagents, and bound antagonist protected nine of
these from reaction. For the mutants in which cysteine was substituted for
residues in the cytoplasmic half of TM4, treatment with the reagents had no
effect on binding, consistent with these residues being inaccessible and with the
low-resolution structure of the homologous rhodopsin, in which TM3 and TM5
occlude the cytoplasmic half of TM4. Although hydrophobicity analysis positions
the C-terminus of TM4 at 4.64, Pro-Pro and Pro-X-Pro motifs, which are known to
disrupt alpha-helices, occur at position 4.59 in a number of homologous GPCRs.
The SCAM data were consistent with a C-terminus at 4.58, but it is also possible
that the alpha-helix extends one additional turn to 4.62 in the D2 receptor,
which has a single Pro at 4.59. In homologous GPCRs, the high degree of sequence
variation between 4.59 and 4.68 is more characteristic of a loop domain than a
helical segment. This region is shown here to be very conserved within
functionally related receptors, suggesting an important functional role for this
putative nonhelical domain. This inference is supported by observed ligand
specific effects of mutations in this region and by the predicted spatial
proximity of this segment to known ligand binding sites in other TMs.
PMID- 11015198
TI - Dipeptide binding to the extended active site of the Streptomyces R61 D-alanyl-D
alanine-peptidase: the path to a specific substrate.
AB - Bacterial cell walls are cross-linked in the final step of biosynthesis by
specific D-alanyl-D-alanine(DD)-peptidases/transpeptidases. The natural
substrates of these enzymes should therefore be segments of peptidoglycan, but
high specificity for such structures has yet to be demonstrated. The binding of
dipeptides to the extended substrate binding site of the Streptomyces R61 DD
peptidase has been studied by means of a fluorescent beta-lactam probe. It was
found that dipeptides of structure Gly-L-Xaa have affinity for a subsite adjacent
to the beta-lactam binding site. Hydrophobic peptides such as Gly-L-Met and Gly-L
aminocaprylic acid had the greatest affinity for this site, with dissociation
constants in each case of 0.19 mM. A combination of this motif with the C
terminal D-alanyl-D-alanine moiety required of a DD-peptidase substrate yielded a
new substrate, glycyl-L-alpha-amino-epsilon-pimelyl-D-alanyl-D-alanine. Steady
state kinetic measurements established this compound as the most specific peptide
substrate yet discovered for a DD-peptidase by at least 3 orders of magnitude
(k(cat) = 69 s(-1), K(m) = 7.9 microM, k(cat)/K(m) = 8.7 x 10(6) s(-1) M(-1));
acylation was rate-determining at saturation. This substrate, presumably not
coincidentally, contains the acyl donor and acceptor moieties, appropriately
separated, of the Streptomyces peptidoglycan structure. This general method of
approach should be of value in the search for specific substrates and inhibitors
(antibiotics) of other DD-peptidases.
PMID- 11015199
TI - Structure-based optimization of peptide inhibitors of mammalian ribonucleotide
reductase.
AB - Mammalian ribonucleotide reductase (mRR), a potential target for cancer
intervention, is composed of two subunits, mR1 and mR2, whose association is
critical for enzyme activity. In this article we describe the structural features
of the mRR-inhibitor Ac-F-c[ELAK]-DF (Peptide 3) while bound to the mR1 subunit
as determined by transferred NOEs. Peptide 3 is a cyclic analogue of the N
acetylated form of the heptapeptide C-terminus of the mR2 subunit (Ac-FTLDADF),
which is the link between the two subunits and previously shown to be the minimal
sequence inhibitor mRR by competing with mR2 for binding to mR1. Structural
refinement employing an ensemble-based, full-relaxation matrix approach resulted
in two structures varying in the conformations of F(1) and the cyclic lactam side
chains of E(2) and K(5). The remainder of the molecule, both backbone and side
chains, is extremely well-defined, with an RMSD of 0.54 A. The structural
features of this conformationally constrained analogue provide unique insight
into the requirements for binding to mR1, critical for further inhibitor
development.
PMID- 11015200
TI - Mapping the functional domains of elongation factor-2 kinase.
AB - A new class of eukaryotic protein kinases that are not homologous to members of
the serine/threonine/tyrosine protein kinase superfamily was recently identified
[Futey, L. M., et al. (1995) J. Biol. Chem. 270, 523-529; Ryazanov, A. G., et al.
(1997) Proc. Natl. Acad. Sci. U.S.A. 94, 4884-4889]. This class includes
eukaryotic elongation factor-2 kinase, Dictyostelium myosin heavy chain kinases
A, B, and C, and several mammalian putative protein kinases that are not yet
fully characterized [Ryazanov, A. G., et al. (1999) Curr. Biol. 9, R43-R45]. eEF
2 kinase is a ubiquitous protein kinase that phosphorylates and inactivates
eukaryotic translational elongation factor-2, and thus can modulate the rate of
polypeptide chain elongation during translation. eEF-2 was the only known
substrate for eEF-2 kinase. We demonstrate here that eEF-2 kinase can efficiently
phosphorylate a 16-amino acid peptide, MH-1, corresponding to the myosin heavy
chain kinase A phosphorylation site in Dictyostelium myosin heavy chains. This
enabled us to develop a rapid assay for eEF-2 kinase activity. To localize the
functional domains of eEF-2 kinase, we expressed human eEF-2 kinase in
Escherichia coli as a GST-tagged fusion protein, and then performed systematic in
vitro deletion mutagenesis. We analyzed eEF-2 kinase deletion mutants for the
ability to autophosphorylate, and to phosphorylate eEF-2 as well as a peptide
substrate, MH-1. Mutants with deletions between amino acids 51 and 335 were
unable to autophosphorylate, and were also unable to phosphorylate eEF-2 and MH
1. Mutants with deletions between amino acids 521 and 725 were unable to
phosphorylate eEF-2, but were still able to autophosphorylate and to
phosphorylate MH-1. The kinases with deletions between amino acids 2 and 50 and
336 and 520 were able to catalyze all three reactions. In addition, the C
terminal domain expressed alone (amino acids 336-725) binds eEF-2 in a
coprecipitation assay. These results suggest that eEF-2 kinase consists of two
domains connected by a linker region. The amino-terminal domain contains the
catalytic domain, while the carboxyl-terminal domain contains the eEF-2 targeting
domain. The calmodulin-binding region is located between amino acids 51 and 96.
The amino acid sequence of the carboxyl-terminal domain of eEF-2 kinase displays
similarity to several proteins, all of which contain repeats of a 36-amino acid
motif that we named "motif 36".
PMID- 11015201
TI - DNA helicase RepA: cooperative ATPase activity and binding of nucleotides.
AB - The steady-state kinetic parameters of the ATPase activity of the homohexameric
DNA helicase RepA and the binding of the fluorescent analogue epsilonADP to RepA
have been studied. ssDNA stimulates RepA ATPase activity optimally at acidic pH
5.3-6.0. The sigmoidal kinetic curves in both the absence and presence of ssDNA
show strong positive cooperativity for ATP hydrolysis, with oligonucleotides
longer than 10mer optimal for ssDNA-stimulated ATPase activity. Fluorescence
titrations show that, at 25 degrees C and in the absence of DNA, the binding of
epsilonADP to RepA is biphasic with three high (K(1) = 1.54 x 10(6) M(-1)) and
three low (K(2) = 4.71 x 10(4) M(-)(1)) affinity binding sites differing by 30-40
fold in binding constants. In the absence of cofactors, RepA melts cooperatively
at T(m) = 65.8 +/- 0.1 degrees C and is more stable in the presence of ATPgammaS,
T(m) = 68.1 +/- 0.2 degrees C (DeltaDeltaG 0.95 kcal/mol), than in the presence
of ADP, T(m) = 66. 5 +/- 0.1 degrees C (DeltaDeltaG 0.29 kcal/mol), indicating
that the additional phosphate group in ATPgammaS has a significant influence on
RepA structure. A model is proposed in which individual subunits of RepA
sequentially and cooperatively perform a multistep ATP hydrolytic cycle.
PMID- 11015202
TI - The binding site for Xenopus glucocorticoid receptor accessory factor and a
single adjacent half-GRE form an independent glucocorticoid response unit.
AB - In Xenopus laevis, transcription of the gamma-fibrinogen subunit gene is
activated by glucocorticoids. Hormone induction is regulated by three
glucocorticoid response element (GRE) half-sites and an additional DNA sequence
which binds a novel hepatocyte nuclear protein, Xenopus glucocorticoid receptor
accessory factor (XGRAF). The XGRAF binding site (GAGTTAA) is located directly
upstream of the most distal half-GRE. The proximity of the binding sites for
XGRAF and the glucocorticoid receptor (GR) led to the hypothesis that these two
sites form a glucocorticoid response unit (GRU). By transfecting DNA into primary
hepatocytes, we showed that this GRU confers hormone responsiveness in the
absence of other half-GREs. The XGRAF binding site enhances function of the half
GRE without itself responding to glucocorticoids. The GRU retains efficacy in
other locations relative to the gamma-fibrinogen gene promoter, further increases
transcription when present in multiple copies, and activates a heterologous
promoter. Despite the contiguity of the XGRAF binding site and half-GRE, the two
sites can be occupied simultaneously in vitro. The binding characteristics
correlate with function since mutations that disrupt concurrent XGRAF and GR
binding also impair transcription. This novel GRU represents a new regulatory
mechanism that may be applicable to other glucocorticoid responsive genes that
lack a full GRE.
PMID- 11015203
TI - Analysis of the RNA-editing reaction of ADAR2 with structural and fluorescent
analogues of the GluR-B R/G editing site.
AB - ADARs are adenosine deaminases responsible for RNA editing reactions that occur
in eukaryotic pre-mRNAs, including the pre-mRNAs of glutamate and serotonin
receptors. Here we describe the generation and analysis of synthetic ADAR2
substrates that differ in structure around an RNA editing site. We find that five
base pairs of duplex secondary structure 5' to the editing site increase the
single turnover rate constant for deamination 17-39-fold when compared to
substrates lacking this structure. ADAR2 deaminates an adenosine in the sequence
context of a natural editing site >90-fold more rapidly and to a higher yield
than an adjacent adenosine in the same RNA structure. This reactivity is
minimally dependent on the base pairing partner of the edited nucleotide;
adenosine at the editing site in the naturally occurring A.C mismatch is
deaminated to approximately the same extent and only 4 times faster than
adenosine in an A.U base pair at this site. A steady-state rate analysis at a
saturating concentration of the most rapidly processed substrate indicates that
product formation is linear with time through at least three turnovers with a
slope of 13 +/- 1.5 nM.min(-1) at 30 nM ADAR2 for a k(ss) = 0.43 +/- 0.05 min(
1). In addition, ADAR2 induces a 3.3-fold enhancement in fluorescence intensity
and a 14 nm blue shift in the emission maximum of a duplex substrate with 2
aminopurine located at the editing site, consistent with a mechanism whereby
ADAR2 flips the reactive nucleotide out of the double helix prior to deamination.
PMID- 11015204
TI - Differential incision of bulky carcinogen-DNA adducts by the UvrABC nuclease:
comparison of incision rates and the interactions of Uvr subunits with lesions of
different structures.
AB - The UvrABC nuclease system from Escherichia coli removes DNA damages induced by a
wide range of chemical carcinogens with variable efficiencies. The interactions
with UvrABC proteins of the following three lesions site-specifically positioned
in DNA, and of known conformations, were investigated: (i) adducts derived from
the binding of the (-)-(7S,8R,9R,10S) enantiomer of 7,8-dihydroxy-9, 10-epoxy
7,8,9,10-tetrahydrobenzo[a]pyrene [(-)-anti-BPDE] by cis-covalent addition to
N(2)-2'-deoxyguanosine [(-)-cis-anti-BP-N(2)-dG], (ii) an adduct derived from the
binding of the (+)-(1R,2S,3S,4R) enantiomer of 1,2-dihydroxy-3,4-epoxy-1,2,3, 4
tetrahydro-5-methylchrysene [(+)-anti-5-MeCDE] by trans addition to N(2)-2'
deoxyguanosine [(+)-trans-anti-MC-N(2)-dG], and (iii) a C8-2'-deoxyguanosine
adduct (C8-AP-dG) formed by reductively activated 1-nitropyrene (1-NP). The
influence of these three different adducts on UvrA binding affinities, formation
of UvrB-DNA complexes by quantitative gel mobility shift analyses, and the rates
of UvrABC incision were investigated. The binding affinities of UvrA varied among
the three adducts. UvrA bound to the DNA adduct (+)-trans-anti-MC-N(2)-dG with
the highest affinity (K(d) = 17 +/- 2 nM) and to the DNA containing C8-AP-dG with
the least affinity (K(d) = 28 +/- 1 nM). The extent of complex formation with
UvrB was also the lowest with the C8-AP-dG adduct. 5' Incisions occurred at the
eighth phosphate from the modified guanine. The major 3' incision site
corresponded to the fifth phosphodiester bond for all three adducts. However,
additional 3' incisions were observed at the fourth and sixth phosphates in the
case of the C8-AP-dG adduct, whereas in the case of the (-)-cis-anti-BP-N(2)-dG
and (+)-trans-anti-MC-N(2)-dG lesions additional 3' cleavage occurred at the
sixth and seventh phosphodiester bonds. Both the initial rate and the extent of
5' and 3' incisions revealed that C8-AP-dG was repaired less efficiently in
comparison to the (-)-cis-anti-BP-N(2)-dG and (+)-trans-anti-MC-N(2)-dG
containing DNA adducts. Our study showed that UvrA recognizes conformational
changes induced by structurally different lesions and that in certain cases the
binding affinities of UvrA and UvrB can be correlated with the incision rates.
The size of the bubble formed around the damaged site with mismatched bases also
appears to influence the incision rates. A particularly noteworthy finding in
this study is that UvrABC repair of a substrate with no base opposite C8-AP-dG
was quite inefficient as compared to the same adduct with a C opposite it. These
findings are discussed in terms of the available NMR solution structures.
PMID- 11015205
TI - Evaluation of the effectiveness of DNA-binding drugs to inhibit transcription
using the c-fos serum response element as a target.
AB - Previous work has demonstrated that sequence-selective DNA-binding drugs can
inhibit transcription factors from binding to their target sites on gene
promoters. In this study, the potency and effectiveness of DNA-binding drugs to
inhibit transcription were assessed using the c-fos promoter's serum response
element (SRE) as a target. The drugs chosen for analysis included the minor
groove binding agents chromomycin A(3) and Hoechst 33342, which bind to G/C-rich
and A/T-rich regions, respectively, and the intercalating agent nogalamycin,
which binds G/C-rich sequences in the major groove. The transcription factors
targeted, Elk-1 and serum response factor (SRF), form a ternary complex (TC) on
the SRE that is necessary and sufficient for induction of c-fos by serum. The
drugs' abilities to prevent TC formation on the SRE in vitro were nogalamycin >
Hoechst 33342 > chromomycin. Their potencies in inhibiting cell-free
transcription and endogenous c-fos expression in NIH3T3 cells, however, were
chromomycin > nogalamycin > Hoechst 33342. The latter order of potency was also
obtained for the drugs' cytotoxicity and inhibition of general transcription as
measured by [(3)H]uridine incorporation. These systematic analyses provide
insight into how drug and transcription factor binding characteristics are
related to drugs' effectiveness in inhibiting gene expression.
PMID- 11015206
TI - Sequence determinants for the recognition of the fork junction DNA containing the
-10 region of promoter DNA by E. coli RNA polymerase.
AB - It has been recently suggested that E. coli RNA polymerase can specifically
recognize a fork junction DNA structure, suggesting a possible role for such
interaction in promoter DNA melting [Guo, Y., and Gralla, J. D. (1998) Proc.
Natl. Acad. Sci. U.S.A. 95, 11655-11660]. We have determined here quantitatively,
using a site-specific binding assay, the effects of base substitutions within the
conserved -10 hexamer in the context of a short fork junction DNA on binding to
RNA polymerase. Adenine at position -11 and thymine at position -7 were found to
be critical for sequence-specific recognition of the DNA. The identities of bases
at positions -9 and -8 were found to be not important for the binding whereas
replacement of bases at positions -12 and -10 had a mild negative effect on the
binding affinity. It was found that for the binding of fork DNA to RNA
polymerase, specific sequence recognition was more important than specific
recognition of fork junction DNA structure. The pattern of relative importance of
bases in the -10 region for binding RNA polymerase was generally consistent with
the sequence conservation pattern observed in nature where positions -11 and -7
are the most conserved. Binding experiments with a series of adenine analogues at
position -11 revealed that the N1 nitrogen of adenine was a critical determinant
for the preference of the adenine at this position, suggesting a mechanism for
the nucleation of promoter DNA melting initiation in which RNA polymerase
destabilizes duplex DNA by directly competing with the thymine of the A-T base
pair for hydrogen bonding to the N1 position of the -11 nontemplate strand
adenine.
PMID- 11015207
TI - Intervesicle cross-linking with integrin alpha IIb beta 3 and cyclic-RGD
lipopeptide. A model of cell-adhesion processes.
AB - We report the synthesis of a new integrin alpha(IIb)beta(3)-specific cyclic
hexapeptide that contains an Arg-Gly-Asp (RGD) sequence and is coupled to a
dimyristoylthioglyceryl anchor. We demonstrate that this ligand is useful to
study specific integrin binding to membrane surfaces. With the help of
biotinylated analogues of the peptide, a spacer of optimal length between the
peptide and lipid moieties was searched for by evaluating the binding strength
with an enzyme-coupled immunosorbent assay (ELISA) and by surface plasmon
resonance (SPR). It was found to be strongly dependent on the length of the
spacer introduced between the biotin and peptide moieties of the ligands, which
consisted either of epsilon-aminohexanoic acid (epsilonAhx) or of epsilonAhx with
two additional glycine units. Best results were obtained with c[Arg-Gly-Asp-D-Phe
Lys(Biot-Ahx-Gly-Gly)-Gly-] with dissociation constants of K(D) = 0.158 microM
from ELISA and K(D) = 1.1 microM from SPR measurements. The analogous
lipopeptide, c[Arg-Gly-Asp-D-Phe-Lys([dimyristoyl-3-thioglyceryl-succinimido
propanoyl]Ahx-Gly-Gly)-Gly], was used as a membrane-anchored integrin ligand. It
is shown by fluorescence microscopy and cryo electron microscopy that integrin
reconstituted into phospholipid vesicles binds to vesicles decorated with the
lipopeptide, forming regularly spaced bridges between the two kinds of vesicles.
The novel integrin-specific ligand allows establishment of new model systems for
systematic studies of the self-organization of integrin clusters and focal
adhesion complexes.
PMID- 11015208
TI - Stathmin slows down guanosine diphosphate dissociation from tubulin in a
phosphorylation-controlled fashion.
AB - Stathmin is an important protein that interacts with tubulin and regulates
microtubule dynamics in a phosphorylation-controlled fashion. Here we show that
the dissociation of guanosine 5'-diphosphate (GDP) from beta-tubulin is slowed 20
fold in the (tubulin)(2)-stathmin ternary complex (T(2)S). The kinetics of GDP or
guanosine 5'-triphosphate (GTP) dissociation from tubulin have been monitored by
the change in tryptophan fluorescence of tubulin upon exchanging 2-amino-6
mercapto-9-beta-ribofuranosylpurine 5'-diphosphate (S6-GDP) for tubulin-bound
guanine nucleotide. At molar ratios of stathmin to tubulin lower than 0.5,
biphasic kinetics were observed, indicating that the dynamics of the complex is
extremely slow, consistent with its high stability. The method was used to
characterize the effects of phosphorylation of stathmin on its interaction with
tubulin. The serine-to-glutamate substitution of all four phosphorylatable
serines of stathmin (4E-stathmin) weakens the stability of the T(2)S complex by
about 2 orders of magnitude. The phosphorylation of serines 16 and 63 in stathmin
has a more severe effect and weakens the stability of T(2)S 10(4)-fold. The rate
of GDP dissociation is lowered only 7-fold and 4-fold in the complexes of tubulin
with 4E-stathmin and diphosphostathmin, respectively. Sedimentation velocity
studies support the conclusions of nucleotide exchange data and show that the
T(2)S complexes formed between tubulin and 4E-stathmin or diphosphostathmin are
less compact than the highly stable T(2)S complex. The correlation between the
effect of phosphorylation of stathmin on the stability of T(2)S complex measured
in vitro and on the function of stathmin in vivo is discussed.
PMID- 11015209
TI - Secondary structure and oligomerization of the E. coli glycerol facilitator.
AB - The Major Intrinsic Proteins are found throughout the bacterial, plant, and
animal kingdoms and are responsible for the rapid transport of water and other
small, polar solutes across membranes. The superfamily includes the aquaporins,
the aquaglyceroporins, and the glycerol facilitators. We have overexpressed and
purified the Escherichia coli inner membrane glycerol facilitator. Approximately
7.5 mg of 95% pure protein is obtained from 1 L of Escherichia coli cells using
immobilized metal affinity chromatography. Well-resolved matrix-assisted laser
desorption ionization mass spectra were obtained by solubilization of the protein
in octyl-beta-D-glucopyranoside (M(r) = 33 650.3; error approximately 0.4%). The
recombinant glycerol facilitator is inserted into the bacterial inner membrane,
is functional, and is inhibited by HgCl(2). Polyacrylamide gel electrophoresis
suggests that the facilitator is predominantly monomeric when solubilized with
dodecyl-beta-D-maltoside, octyl-beta-D-glucopyranoside, and sodium dodecyl
sulfate, but that it self-associates, forming soluble oligomers when urea is used
during extraction. Similar oligomeric species are demonstrated to exist in the
bacterial membrane by chemical cross-linking experiments. Circular dichroism
analysis shows that the protein is predominantly alpha-helical. Helix content is
significantly higher in protein prepared in the absence of urea (42-55%) than in
its presence (32%). A possible role for the facilitator oligomers in interactions
with, and regulation of, the glycerol kinase is discussed.
PMID- 11015210
TI - Structural basis of the anionic interface preference and kcat* activation of
pancreatic phospholipase A2.
AB - Pancreatic phospholipase A(2) (PLA2) shows a strong preference for the binding to
the anionic interface and a consequent allosteric activation. In this paper, we
show that virtually all the preference is mediated through 3 (Lys-53, -56, and
120) of the 12 cationic residues of bovine pancreatic PLA2. The lysine-to
methionine substitution enhances the binding of the enzyme to the zwitterionic
interface, and for the K53,56,120M triple mutant at the zwitterionic interface is
comparable to that for the wild type (WT) at the anionic interface. In the
isomorphous crystal structure, the backbone folding of K53,56M K120,121A and WT
are virtually identical, yet a significant change in the side chains of certain
residues, away from the site of substitution, mostly at the putative contact site
with the interface (i-face), is discernible. Such reciprocity, also supported by
the spectroscopic results for the free and bound forms of the enzyme, is expected
because a distal structural change that perturbs the interfacial binding could
also affect the i-face. The results show that lysine-to-methionine substitution
induces a structural change that promotes the binding of PLA2 to the interface as
well as the substrate binding to the enzyme at the interface. The kinetic results
are consistent with a model in which the interfacial Michaelis complex exists in
two forms, and the complex that undergoes the chemical step is formed by the
charge compensation of Lys-53 and -56. Analysis of the incremental changes in the
kinetic parameters shows that the charge compensation of Lys-53 and -56
contributes to the activation and that of Lys-120 contributes only to the
structural change that promotes the stability of the Michaelis complex at the
interface. The charge compensation effects on these three residues also account
for the differences in the anionic interface preference of the evolutionarily
divergent secreted PLA2.
PMID- 11015211
TI - Cooperative modulation of protein kinase CK2 by separate domains of its
regulatory beta-subunit.
AB - Protein kinase CK2 ("casein kinase 2") holoenzyme is composed of two catalytic
(alpha and/or alpha') and two regulatory beta-subunits. A truncated form of the
beta-subunit lacking its C-terminal region (betaDelta171-215) has lost the
ability to stably associate with the catalytic subunits and to display a number
of properties which are mediated by structural elements still present in its
sequence, notably down-regulation of catalytic activity, autophosphorylation, and
responsiveness to polycationic effectors. All these functions are restored by
simultaneous addition of a synthetic peptide reproducing the deleted fragment,
beta170-215, which is able to associate with the catalytic subunits and to
stimulate catalytic activity. This peptide includes a segment displaying
significant sequence similarity with a region of cyclin A which interacts with
the PSTAIRE motif of CDK2 eliciting its catalytic activity. A peptide reproducing
this sequence (beta181-203), but not its derivative in which three nonpolar side
chains have been replaced by polar ones, interacts with the alpha-subunit and
stimulates its catalytic activity; it also partially restores the ability of
truncated betaDelta171-215 to autophosphorylate. These data disclose the
essential role of a structural module located between residues 181 and 203 in
conferring regulatory properties to the beta-subunit of CK2.
PMID- 11015212
TI - Myosin motor domain lever arm rotation is coupled to ATP hydrolysis.
AB - We have investigated coupling of lever arm rotation to the ATP binding and
hydrolysis steps for the myosin motor domain. In several current hypotheses of
the mechanism of force production by muscle, the primary mechanical feature is
the rotation of a lever arm that is a subdomain of the myosin motor domain. In
these models, the lever arm rotates while the myosin motor domain is free, and
then reverses the rotation to produce force while it is bound to actin. These
mechanical steps are coupled to steps in the ATP hydrolysis cycle. Our hypothesis
is that ATP hydrolysis induces lever arm rotation to produce a more compact motor
domain that has stored mechanical energy. Our approach is to use transient
electric birefringence techniques to measure changes in hydrodynamic size that
result from lever arm rotation when various ligands are bound to isolated
skeletal muscle myosin motor domain in solution. Results for ATP and CTP, which
do support force production by muscle fibers, are compared to those of ATPgammaS
and GTP, which do not. Measurements are also made of conformational changes when
the motor domain is bound to NDP's and PP(i) in the absence and presence of the
phosphate analogue orthovanadate, to determine the roles the nucleoside moieties
of the nucleotides have on lever arm rotation. The results indicate that for the
substrates investigated, rotation does not occur upon substrate binding, but is
coupled to the NTP hydrolysis step. The data are consistent with a model in which
only substrates that produce a motor domain-NDP-P(i) complex as the steady-state
intermediate make the motor domain more compact, and only those substrates
support force production.
PMID- 11015213
TI - Equilibrium folding of dimeric class mu glutathione transferases involves a
stable monomeric intermediate.
AB - The conformational stabilities of two homodimeric class mu glutathione
transferases (GSTM1-1 and GSTM2-2) were studied by urea- and guanidinium chloride
induced denaturation. Unfolding is reversible and structural changes were
followed with far-ultraviolet circular dichroism, tryptophan fluorescence, enzyme
activity, chemical cross-linking, and size-exclusion chromatography. Disruption
of secondary structure occurs as a monophasic transition and is independent of
protein concentration. Changes in tertiary structure occur as two transitions;
the first is protein concentration dependent, while the second is weakly
dependent (GSTM1-1) or independent (GSTM2-2). The second transition corresponds
with the secondary structure transition. Loss in catalytic activity occurs as two
transitions for GSTM1-1 and as one transition for GSTM2-2. These transitions are
dependent upon protein concentration. The first deactivation transition coincides
with the first tertiary structure transition. Dimer dissociation occurs prior to
disruption of secondary structure. The data suggest that the equilibrium
unfolding/refolding of the class mu glutathione transferases M1-1 and M2-2
proceed via a three-state process: N(2) <--> 2I <--> 2U. Although GSTM1-1 and
GSTM2-2 are homologous (78% identity/94% homology), their N(2) tertiary
structures are not identical. Dissociation of the GSTM1-1 dimer to structured
monomers (I) occurs at lower denaturant concentrations than for GSTM2-2. The
monomeric intermediate for GSTM1-1 is, however, more stable than the intermediate
for GSTM2-2. The intermediates are catalytically inactive and display nativelike
secondary structure. Guanidinium chloride-induced denaturation yields monomeric
intermediates, which have a more loosely packed tertiary structure displaying
enhanced solvent exposure of its tryptophans and enhanced ANS binding. The three
state model for the class mu enzymes is in contrast to the equilibrium two-state
models previously proposed for representatives of classes alpha/pi/Sj26 GSTs.
Class mu subunits appear to be intrinsically more stable than those of the other
GST classes.
PMID- 11015214
TI - Acid denaturation of recombinant porcine growth hormone: formation and self
association of folding intermediates.
AB - We have investigated the conformational changes incurred during the acid-induced
unfolding and self-association of recombinant porcine growth hormone (pGH).
Acidification (pH 8 to pH 2) of pGH resulted in intrinsic fluorescence, UV
absorbance, and near-UV CD transitions centered at pH 4.10. At pH 2.0, a red
shift in the fluorescence emission maximum of approximately 3 nm and a 15% loss
of the far-UV CD signal at 222 nm imply that the protein did not become
extensively unfolded. Acidification in the presence of 4 M urea resulted in
similar pH-dependent transitions. However, these occurred at a higher pH
(approximately 5.2). At pH 2.0 + 4 M urea, an 8 nm red shift in the fluorescence
emission maximum suggests that unfolding was greater than in the absence of urea.
The presence of a prominent peak centered at 298 nm in the near-UV CD spectrum,
which is absent without urea, signifies further differences in the intermediates
generated at pH 2. Sedimentation equilibrium experiments in the analytical
ultracentrifuge showed that native pGH and the partially unfolded intermediates
reversibly self-associate. Self-association was strongly promoted at pH 2 while
urea reduced self-association at both pH 8 and pH 2. These results demonstrate
that acidification of pGH in the absence or presence of 4 M urea induced the
formation of molten globule-like states with measurable differences in
conformation. Similarities and differences in these structural conformations with
respect to other growth hormones are discussed.
PMID- 11015215
TI - Cooperative assembly of a nativelike ubiquitin structure through peptide fragment
complexation: energetics of peptide association and folding.
AB - Peptide fragments corresponding to the N- and C-terminal portions of bovine
ubiquitin, U(1-35) and U(36-76), are shown by NMR to associate in solution to
form a complex of modest stability (Kassn approximately 1.4 x 10(5) M(-1) at pH
7.0), with NMR features characteristic of a nativelike structure. The complex
undergoes cold denaturation, with temperature-dependent estimates of stability
from NMR indicating a DeltaC(p) degrees for fragment complexation in good
agreement with that determined for native ubiquitin, suggesting that fragment
association results in the burial of a similar hydrophobic surface area. The
stability of the complex shows appreciable pH dependence, suggesting that ionic
interactions on the surface of the protein contribute significantly. However,
denaturation studies of native ubiquitin in the presence of guanidine
hydrochloride (Gdn.HCl) show little pH dependence, suggesting that ionic
interactions may be "screened" by the denaturant, as recently suggested.
Examination of the conformation of the isolated peptide fragments has shown
evidence for a low population of nativelike structure in the N-terminal beta
hairpin (residues 1-17) and weak nascent helical propensity in the helical
fragment (residues 21-35). In contrast, the C-terminal peptide (36-76) shows
evidence in aqueous solution, from some Halpha chemical shifts, for nonnative phi
and psi angles; nonnative alpha-helical structure is readily induced in the
presence of organic cosolvents, indicating that tertiary interactions in both
native ubiquitin and the folded fragment complex strongly dictate its structural
preference. The data suggest that the N-terminal fragment (1-35), where
interaction between the helix and hairpin requires the minimum loss of
conformational entropy, may provide the nucleation site for fragment
complexation.
PMID- 11015216
TI - Thermodynamic and structural studies of cavity formation in proteins suggest that
loss of packing interactions rather than the hydrophobic effect dominates the
observed energetics.
AB - The hydrophobic effect is widely believed to be an important determinant of
protein stability. However, it is difficult to obtain unambiguous experimental
estimates of the contribution of the hydrophobic driving force to the overall
free energy of folding. Thermodynamic and structural studies of large to small
substitutions in proteins are the most direct method of measuring this
contribution. We have substituted the buried residue Phe8 in RNase S with
alanine, methionine, and norleucine. Binding thermodynamics and structures were
characterized by titration calorimetry and crystallography, respectively. The
crystal structures of the RNase S F8A, F8M, and F8Nle mutants indicate that the
protein tolerates the changes without any main chain adjustments. The correlation
of structural and thermodynamic parameters associated with large to small
substitutions was analyzed for nine mutants of RNase S as well as 32 additional
cavity-containing mutants of T4 lysozyme, human lysozyme, and barnase. Such
substitutions were typically found to result in negligible changes in DeltaC(p)()
and positive values of both DeltaDeltaH degrees and DeltaDeltaS of folding.
Enthalpic effects were dominant, and the sign of DeltaDeltaS is the opposite of
that expected from the hydrophobic effect. Values of DeltaDeltaG degrees and
DeltaDeltaH degrees correlated better with changes in packing parameters such as
residue depth or occluded surface than with the change in accessible surface area
upon folding. These results suggest that the loss of packing interactions rather
than the hydrophobic effect is a dominant contributor to the observed energetics
for large to small substitutions. Hence, estimates of the magnitude of the
hydrophobic driving force derived from earlier mutational studies are likely to
be significantly in excess of the actual value.
PMID- 11015217
TI - Contribution of salt bridges near the surface of a protein to the conformational
stability.
AB - Salt bridges play important roles in the conformational stability of proteins.
However, the effect of a surface salt bridge on the stability remains
controversial even today; some reports have shown little contribution of a
surface salt bridge to stability, whereas others have shown a favorable
contribution. In this study, to elucidate the net contribution of a surface salt
bridge to the conformational stability of a protein, systematic mutant human
lysozymes, containing one Glu to Gln (E7Q) and five Asp to Asn mutations (D18N,
D49N, D67N, D102N, and D120N) at residues where a salt bridge is formed near the
surface in the wild-type structure, were examined. The thermodynamic parameters
for denaturation between pH 2.0 and 4.8 were determined by use of a differential
scanning calorimeter, and the crystal structures were analyzed by X-ray
crystallography. The denaturation Gibbs energy (DeltaG) of all mutant proteins
was lower than that of the wild-type protein at pH 4, whereas there was little
difference between them near pH 2. This is caused by the fact that the Glu and
Asp residues are ionized at pH 4 but protonated at pH 2, indicating a favorable
contribution of salt bridges to the wild-type structure at pH 4. Each
contribution was not equivalent, but we found that the contributions correlate
with the solvent inaccessibility of the salt bridges; the salt bridge
contribution was small when 100% accessible, while it was about 9 kJ/mol if 100%
inaccessible. This conclusion indicates how to reconcile a number of conflicting
reports about role of surface salt bridges in protein stability. Furthermore, the
effect of salts on surface salt bridges was also examined. In the presence of 0.2
M KCl, the stability at pH 4 decreased, and the differences in stability between
the wild-type and mutant proteins were smaller than those in the absence of
salts, indicating the compensation to the contribution of salt bridges with
salts. Salt bridges with more than 50% accessibility did not contribute to the
stability in the presence of 0.2 M KCl.
PMID- 11015218
TI - The residual pro-part of cathepsin C fulfills the criteria required for an
intramolecular chaperone in folding and stabilizing the human proenzyme.
AB - The 13.5 kDa N-terminal part of the propeptide remains associated with mature
cathepsin C after proteolytic activation and excision of the activation peptide.
This residual pro-part, isolated from the recombinant enzyme, folds spontaneously
and rapidly to a stable, compact monomer with secondary structure and stable
tertiary interactions. Folding and unfolding kinetics of the residual pro-part
with intact disulfides are complex, and accumulation of transient intermediates
is observed. The cleaved form of the pro-part isolated from natural human
cathepsin C also folds, suggesting that the intact form comprises two folding
domains. The linkages of the two disulfide bridges have been established as 30
118 and 54-136 for the native enzyme. The native disulfide bonds can be re-formed
from the fully reduced and denatured state by oxidative refolding, resulting in a
domain that is spectroscopically indistinguishable from the original refolded
residual pro-part. Both disulfides are solvent-exposed and can be reduced in the
absence of denaturant. The reduced form retains most or all of the native
tertiary structure and is only approximately 2 kcal.mol(-1) less stable than the
oxidized form. It folds fast relative to the rate of biosynthesis, to the same
conformation as the oxidized form. Folding and disulfide formation are
sequential. These results indicate that the proenzyme folds sequentially in vivo
and that the residual pro-part constitutes a rapidly and independently folding
domain that stabilizes the mature enzyme. It thus fulfills the criteria required
of an intramolecular chaperone. It may also be involved in stabilizing the
tetrameric structure of the mature enzyme.
PMID- 11015219
TI - Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by
cryogenic X-ray diffraction.
AB - The three-dimensional structure of a possible intermediate in the hydration
reaction of cyanamide to urea catalyzed by human carbonic anhydrase II (hCAII)
has been determined by cryocrystallographic techniques. The crystal structure
shows that two different adducts are formed under the experimental conditions and
that they have different occupancy in the crystal. The high occupancy form
consists of a binary hCAII-cyanamide complex where the substrate has replaced the
zinc-bound hydroxide anion present in the native enzyme, maintaining the
tetrahedral geometry around the metal ion. The second, low-occupancy form
consists of a hCAII-cyanamide-water ternary complex where the catalytic zinc ion,
still being bound to cyanamide, is approached by a water molecule in a five
coordinate adduct. While the first form can be considered a nonproductive
complex, the second form may represent an intermediate state of the catalyzed
reaction where the water molecule is about to perform a nucleophilic attack on
the zinc-activated cyanamide substrate. The structural evidence is consistent
with the kinetic data previously reported about this recently described
hydrolytic reaction catalyzed by hCAII, and indicates that a different mechanism
with respect to that generally accepted for the physiologic carbon dioxide
hydration reaction may be adopted by the enzyme, depending on the substrate
chemical properties.
PMID- 11015220
TI - Role of metals in the reaction catalyzed by protein farnesyltransferase.
AB - Protein farnesyltransferase catalyzes the posttranslational farnesylation of
several proteins involved in signal transduction, including Ras, and is a target
enzyme for antitumor therapies. Efficient product formation catalyzed by protein
farnesyltransferase requires an enzyme-bound zinc cation and high concentrations
of magnesium ions. In this work, we have measured the pH dependence of the
chemical step of product formation, determined under single-turnover conditions,
and have demonstrated that the prenylation rate constant is enhanced by two
deprotonations. Substitution of the active site zinc by cadmium demonstrated that
one of the ionizations reflects deprotonation of the metal-coordinated thiol of
the peptide "CaaX" motif, pK(a1) = 6.0. These data provide additional evidence
for the direct involvement of a metal-coordinated sulfur nucleophile in
catalysis. The second ionization was assigned to a hydroxyl on the pyrophosphate
moiety of farnesyl pyrophosphate, pK(a2) = 7.4. Deprotonation of this group is
important for binding of magnesium. This second ionization is not observed for
catalysis in the absence of magnesium or when the substrate is farnesyl
monophosphate. These data indicate that the maximal rate constant for prenylation
requires formation of a zinc-coordinated thiolate nucleophile and enhancement of
the electrophilic character at C1 of the farnesyl chain by magnesium ion
coordination of the pyrophosphate leaving group.
PMID- 11015221
TI - Mass spectral characterization of lipooligosaccharides from Haemophilus
influenzae 2019.
AB - Lipooligosaccharide (LOS) glycoforms from Haemophilus influenzae 2019 were
profiled using the high-resolution and accurate mass capabilities of Fourier
transform ion cyclotron resonance (FT-ICR) mass spectrometry. Sequence and
linkage for two previously unknown LOS glycoforms were subsequently obtained
through MSn analyses on FT-ICR and quadrupole ion trap (qIT) instruments. MSn
analysis of negative ion precursors confirmed structural details within the lipid
moiety, while CID spectra of sodiated precursor ions provided monosaccharide
sequence and linkage for the oligosaccharide portion of the molecule. Results
obtained in this study indicate that extensive heterogeneity exists within the
oligosaccharide moieties in LOS from H. influenzae 2019. More importantly, the
data suggest that additional hexose moieties, which are added onto the LOS, are
not simple extensions of one particular core structure but rather that structural
isomers with different connectivities are present within the heterogeneous
mixture.
PMID- 11015222
TI - Inositol-1-phosphate synthase from Archaeoglobus fulgidus is a class II aldolase.
AB - A gene putatively identified as the Archaeoglobus fulgidus inositol-1-phosphate
synthase (IPS) gene was overexpressed to high level (about 30-40% of total
soluble cellular proteins) in Escherichia coli. The recombinant protein was
purified to homogeneity by heat treatment followed by two column chromatographic
steps. The native enzyme was a tetramer of 168 +/- 4 kDa (subunit molecular mass
of 44 kDa). At 90 degrees C the K(m) values for glucose-6-phosphate and NAD(+)
were estimated as 0.12 +/- 0.04 mM and 5.1 +/- 0.9 microM, respectively. Use of
(D)-[5-(13)C]glucose-6-phosphate as a substrate confirmed that the
stereochemistry of the product of the IPS reaction was L-myo-inositol-1
phosphate. This archaeal enzyme, with the highest activity at its optimum growth
temperature among all IPS reported (k(cat) = 9.6 +/- 0.4 s(-1) with an estimated
activation energy of 69 kJ/mol), was extremely heat stable. However, the most
unique feature of A. fulgidus IPS was that it absolutely required divalent metal
ions for activity. Zn(2+) and Mn(2+) were the best activators with K(D)
approximately 1 microM, while NH(4)(+) (a critical activator for all the other
characterized IPS enzymes) had no effect on the enzyme. These properties
suggested that this archaeal IPS was a class II aldolase. In support of this,
stoichiometric reduction of NAD(+) to NADH could be followed
spectrophotometrically when EDTA was present along with glucose-6-phosphate.
PMID- 11015223
TI - Resonance Raman studies indicate a unique heme active site in prostaglandin H
synthase.
AB - Prostaglandin H synthase isoforms 1 and 2 (PGHS-1 and -2) catalyze the first two
steps in the biosynthesis of prostaglandins. Resonance Raman spectroscopy was
used to characterize the PGHS heme active site and its immediate environment.
Ferric PGHS-1 has a predominant six-coordinate high-spin heme at room
temperature, with water as the sixth ligand. The proximal histidine ligand (or
the distal water ligand) of this hexacoordinate high-spin heme species was
reversibly photolabile, leading to a pentacoordinate high-spin ferric heme iron.
Ferrous PGHS-1 has a single species of five-coordinate high-spin heme, as evident
from nu(2) at 1558 cm(-1) and nu(3) at 1471 cm(-1). nu(4) at 1359 cm(-1)
indicates that histidine is the proximal ligand. A weak band at 226-228 cm(-1)
was tentatively assigned as the Fe-His stretching vibration. Cyanoferric PGHS-1
exhibited a nu(Fe)(-)(CN) line at 446 cm(-1) and delta(Fe)(-)(C)(-)(N) at 410 cm(
1), indicating a "linear" Fe-C-N binding conformation with the proximal
histidine. This linkage agrees well with the open distal heme pocket in PGHS-1.
The ferrous PGHS-1 CO complex exhibited three important marker lines: nu(Fe)(
)(CO) (531 cm(-1)), delta(Fe)(-)(C)(-)(O) (567 cm(-1)), and nu(C)(-)(O) (1954 cm(
1)). No hydrogen bonding was detected for the heme-bound CO in PGHS-1. These
frequencies markedly deviated from the nu(Fe)(-)(CO)/nu(C)(-)(O) correlation
curve for heme proteins and porphyrins with a proximal histidine or imidazolate,
suggesting an extremely weak bond between the heme iron and the proximal
histidine in PGHS-1. At alkaline pH, PGHS-1 is converted to a second CO binding
conformation (nu(Fe)(-)(CO): 496 cm(-1)) where disruption of the hydrogen bonding
interactions to the proximal histidine may occur.
PMID- 11015225
TI - Spectroscopic studies of zinc(II)- and cobalt(II)-associated Escherichia coli
formamidopyrimidine-DNA glycosylase: extended X-ray absorption fine structure
evidence for a metal-binding domain.
AB - Formamidopyrimidine-DNA glycosylase (Fpg) is a 30.2 kDa protein that plays an
important role in the base excision repair of oxidatively damaged DNA in
Escherichia coli. Sequence analysis and genetic evidence suggest that zinc is
associated with a C4-type motif, C(244)-X(2)-C(247)-X(16)-C(264)-X(2)-C(267),
located at the C-terminus of the protein. The zinc-associated motif has been
shown to be essential for damaged DNA recognition. Extended X-ray absorption fine
structure (EXAFS) spectra collected on the zinc-associated protein (ZnFpg) in the
lyophilized state and in 10% frozen aqueous glycerol solution show directly that
the metal is coordinated to the sulfur atom of four cysteine residues. The
average Zn-S bond length is 2.33 +/- 0.01 and 2.34 +/- 0.01 A, respectively, in
the lyophilized state and in 10% frozen aqueous glycerol solution. Fpg was also
expressed in minimal medium supplemented with cobalt nitrate to yield a blue
colored protein that was primarily cobalt-associated (CoFpg). The profiles of the
circular dichroism spectra for CoFpg and ZnFpg are identical, suggesting that the
substitution of Co(2+) for Zn(2+) does not alter the structure of Fpg. A similar
conclusion is reached upon the analysis of two-dimensional (15)N/(1)H HSQC
spectra of uniformly (15)N-labeled samples of ZnFpg and CoFpg; the spectra are
similar and display features characteristic of a structured protein. Biochemical
assays with a 54 nt DNA oligomer containing 7, 8-dihydro-8-oxoguanine at a
specific location show that CoFpg and ZnFpg are equally active at cleaving the
DNA at the site of the oxidized guanine. EXAFS spectra of CoFpg indicate that the
cobalt is coordinated to the sulfur atom of four cysteine residues with an
average Co-S bond length of 2.28 +/- 0.01 and 2.29 +/- 0.01 A, respectively, in
the lyophilized state and in 10% frozen aqueous glycerol solution. The structural
similarity between CoFpg and ZnFpg suggests that it is biologically relevant to
use the paramagnetic properties of Co(2+) as a structural probe.
PMID- 11015224
TI - UreE stimulation of GTP-dependent urease activation in the UreD-UreF-UreG-urease
apoprotein complex.
AB - The activation of metal-containing enzymes often requires the participation of
accessory proteins whose roles are poorly understood. In the case of Klebsiella
aerogenes urease, a nickel-containing enzyme, metallocenter assembly requires
UreD, UreF, and UreG acting as a protein chaperone complex and UreE serving as a
nickel metallochaperone. Urease apoprotein within the UreD-UreF-UreG-urease
apoprotein complex is activated to wild-type enzyme activity levels under
physiologically relevant conditions (100 microM bicarbonate and 20 microM Ni2+)
in a process that requires GTP and UreE. The GTP concentration needed for optimal
activation is greatly reduced in the presence of UreE compared to that required
in its absence. The amount of UreE provided is critical, with maximal activation
observed at a concentration equal to that of Ni2+. On the basis of its ability to
facilitate urease activation in the presence of chelators, UreE is proposed to
play an active role in transferring Ni2+ to urease apoprotein. Studies involving
site-directed variants of UreE provide evidence that His96 has a direct role in
metal transfer. The results presented here parallel those obtained from previous
in vivo studies, demonstrating the relevance of this in vitro system to the
cellular metallocenter assembly process.
PMID- 11015226
TI - Proteolytic activation of recombinant pro-memapsin 2 (pro-beta-secretase) studied
with new fluorogenic substrates.
AB - Memapsin 2 (beta-secretase), a membrane-anchored aspartic protease, is involved
in the cleavage of beta-amyloid precursor protein to form beta-amyloid peptide.
The primary structure of memapsin 2 suggests that it is synthesized in vivo as
pro-memapsin 2 and converted to memapsin 2 by an activating protease [Lin et al.
(2000) Proc. Natl. Acad. Sci. U.S.A. 97, 1456-1460]. To simulate this activation
mechanism and to produce stable mature memapsin 2 for kinetic/specificity
studies, we have investigated the activation of recombinant pro-memapsin 2 by
several proteases with trypsin-like specificity. Clostripain, kallikrein, and
trypsin increased the activity of pro-memapsin 2. Clostripain activation was
accompanied by the cleavage of the pro region to form mainly two activation
products, Leu(30p)- and Gly(45p)-memapsin 2. Another activation product, Leu(28p)
memapsin 2, was also purified. Kinetics of the activated memapsin 2 were compared
with pro-memapsin 2 using two new fluorogenic substrates, Arg-Glu(5-[(2
aminoethyl)amino]naphthalene-1-sulfonic acid (EDANS))-Glu-Val-Asn-Leu-Asp-Ala-Glu
Phe-Lys(4-(4-dimethylaminophe nyl azo)benzoic acid (DABCYL))-Arg and (7
methoxycoumarin-4-yl)acetyl (MCA))-Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys(2,4
dinitrophenyl (DNP)). These results establish that the activity of pro-memapsin 2
stems from a part-time and reversible uncovering of its active site by its pro
region. Proteolytic removal of part of the pro-peptide at Leu(28p) or Gly(45p),
which diminishes the affinity of the shortened pro-peptide to the active site,
results in activated memapsin 2. These results also suggest that Glu(33p)
memapsin 2 observed in the cells expressing this enzyme [Vassar et al. (1999)
Science 286, 735-741; Yan et al. (1999) Nature 402, 533-537] is an active
intermediate of in vivo activation, or that the peptide Glu(33p)-Arg(44p) may
serve a regulatory role.
PMID- 11015227
TI - "Paper-clip" type triple helix formation by 5'-d-(TC)3Ta(CT)3Cb(AG)3 (a and b = 0
4) as a function of loop size with and without the pseudoisocytosine base in the
Hoogsteen strand.
AB - The formation of a DNA "paper-clip" type triple helix (triplex) with a common
sequence 5'-d-(TC)(3)T(a)()(CT)(3)C(b)()(AG)(3) (a and b = 0-4) was studied by UV
thermal melting experiments and CD spectra. These DNA oligomers form triplexes
and duplexes under slightly acidic and neutral conditions, respectively. The
stability of the formed triplexes (at pH 4.5) or duplexes (at pH 7.0 or 8.0) does
not vary significantly with the size of the loops (a and b = 1-4). At pH 6.0, the
triplex stability is, however, a function of a and b. It is also interesting to
note that the oligomer 5'-d-(TC)(3)(CT)(3)(AG)(3) (a and b = 0) forms a stable
triplex at pH 4.5 with a slightly lower T(m) value, due to dissociation of a base
triad at one end and a distorted base triad at the other, observed by (1)H NMR.
Thus, we have here a model system, 5'-d-(TC)(3)T(a)(CT)(3)C(b)(AG)(3), that could
form a triplex effectively with (a and b = 1-4) and without (a and b = 0) loops
under acidic conditions. In addition, the triplex formation of oligomers with
replacement of one, two, or three 2'-deoxycytidine in the Hoogsteen strand by
either 2'-deoxypseudoisocytidine (D) or 2'-O-methylpseudoisocytidine (M) was also
studied in the sequence 5'-d-(TX)(3)T(2)(CT)(3)C(2)(AG)(3) (where X is C, D, or
M). Both CD spectra and UV melting results showed that only D3 [(TX)(3) =
(TD)(3)] and M3 [(TX)(3) = (TM)(3)] were able to form the paper-clip structure
under both neutral and acidic conditions. This is because the N(3)H of a
pseudoisocytosine base can serve as a proton donor without protonation. We hereby
proved that the 2'-deoxypseudoisocytidine, similar to 2'-O
methylpseudoisocytidine, could replace 2'-deoxycytidine in the Hoogsteen strand
to provide triplex formation at neutral pH.
PMID- 11015228
TI - Multiple folding pathways for the P4-P6 RNA domain.
AB - We recently described site-specific pyrene labeling of RNA to monitor Mg(2+)
dependent equilibrium formation of tertiary structure. Here we extend these
studies to follow the folding kinetics of the 160-nucleotide P4-P6 domain of the
Tetrahymena group I intron RNA, using stopped-flow fluorescence with
approximately 1 ms time resolution. Pyrene-labeled P4-P6 was prepared using a new
phosphoramidite that allows high-yield automated synthesis of
oligoribonucleotides with pyrene incorporated at a specific 2'-amino-2'
deoxyuridine residue. P4-P6 forms its higher-order tertiary structure rapidly,
with k(obs) = 15-31 s(-1) (t(1/2) approximately 20-50 ms) at 35 degrees C and
[Mg(2+)] approximately 10 mM in Tris-borate (TB) buffer. The folding rate
increases strongly with temperature from 4 to 45 degrees C, demonstrating a large
activation enthalpy DeltaH(double dagger) approximately 26 kcal/mol; the
activation entropy DeltaS(double dagger) is large and positive. In low ionic
strength 10 mM sodium cacodylate buffer at 35 degrees C, a slow (t(1/2)
approximately 1 s) folding component is also observed. The folding kinetics are
both ionic strength- and temperature-dependent; the slow phase vanishes upon
increasing [Na(+)] in the cacodylate buffer, and the kinetics switch completely
from fast at 30 degrees C to slow at 40 degrees C. Using synchrotron hydroxyl
radical footprinting, we confirm that fluorescence monitors the same kinetic
events as hydroxyl radical cleavage, and we show that the previously reported
slow P4-P6 folding kinetics apply only to low ionic strength conditions. One
model to explain the fast and slow folding kinetics postulates that some tertiary
interactions are present even without Mg(2+) in the initial state. The fast
kinetic phase reflects folding that is facilitated by these interactions, whereas
the slow kinetics are observed when these interactions are disrupted at lower
ionic strength and higher temperature.
PMID- 11015229
TI - Spin-label electron spin resonance studies on the mode of anchoring and vertical
location of the N-acyl chain in N-acylphosphatidylethanolamines.
AB - Electron spin resonance (ESR) studies have been performed on N-myristoyl
dimyristoylphosphatidylethanolamine (N-14-DMPE) membranes using both
phosphatidylcholines spin-labeled at different positions in the sn-2 acyl chain
and N-acyl phosphatidylethanolamines spin-labeled in the N-acyl chain to
characterize the location and mobility of the N-acyl chain in the lipid
membranes. Comparison of the positional dependences of the spectral data for the
two series of spin-labeled lipids suggests that the N-acyl chain is positioned at
approximately the same level as the sn-2 chain of the phosphatidylcholine spin
label. Further, similar conclusions are reached when the ESR spectra of the N
acyl PE spin-labels in dimyristoylphosphatidylcholine (DMPC) or
dimyristoylphosphatidylethanolamine (DMPE) host matrixes are compared with those
of phosphatidylcholine spin-labels in these two lipids. Finally, the chain
ordering effect of cholesterol has also been found to be similar for the N-acyl
PE spin-label and PC spin-labels, when the host matrix is either DMPC and
cholesterol or N-14-DMPE and cholesterol at a 6:4 mole ratio. In both cases, the
gel-to-liquid crystalline phase transition is completely abolished but
cholesterol perturbs the gel-phase mobility of N-14-DMPE more readily than that
of DMPC. These results demonstrate that the long N-acyl chains are anchored
firmly in the hydrophobic interior of the membrane, in an orientation that is
parallel to that of the O-acyl chains, and are located at nearly the same
vertical position as that of the sn-2 acyl chains in the lipid bilayer. There is
a high degree of dynamic compatibility between the N-acyl chains and the O-acyl
chains of the lipid bilayer core, although bilayers of N-acyl
phosphatidylethanolamines possess a more hydrophobic interior than
phosphatidylcholine bilayers. These results provide a structural basis for
rationalizing the biological properties of NAPEs.
PMID- 11015230
TI - Dynamin is membrane-active: lipid insertion is induced by phosphoinositides and
phosphatidic acid.
AB - Dynamin is a large GTPase involved in the regulation of membrane constriction and
fission during receptor-mediated endocytosis. Dynamin contains a pleckstrin
homology domain which is essential for endocytosis and which binds to anionic
phospholipids. Here, we show for the first time that dynamin is a membrane-active
molecule capable of penetrating into the acyl chain region of membrane lipids.
Lipid penetration is strongly stimulated by phosphatidic acid (PA),
phosphatidylinositol 4-phosphate, and phosphatidylinositol 4, 5-bisphosphate.
Though binding is more efficient in the presence of the phosphoinositides, a much
larger part of the dynamin molecule penetrates into PA-containing mixed-lipid
systems. Thus, local lipid metabolism will dramatically influence dynamin-lipid
interactions, and dynamin-lipid interactions are likely to play an important role
in dynamin-dependent endocytosis. Our data suggest that dynamin is directly
involved in membrane destabilization, a prerequisite to membrane fission.
PMID- 11015231
TI - Striking stabilization of Arc repressor by an engineered disulfide bond.
AB - A solvent-exposed Cys11-Cys11' disulfide bond was designed to link the
antiparallel strands of the beta sheet both in the Arc repressor dimer and in a
single-chain variant in which the Arc subunits are connected by a 15-residue
peptide tether. In both proteins, the presence of the disulfide bond increased
the T(m) by approximately 40 degrees C. In the single-chain background, the
disulfide bond stabilized Arc by 8.5 kcal/mol relative to the reduced form, a
significantly larger degree of stabilization than caused by other engineered
disulfides and most natural disulfides. This exceptional stabilization arises
from a modest effective concentration of the Cys11-Cys11' disulfide in the native
state (71 M) and an anomalously low effective concentration in the denatured
state (40 microM). Disulfide cross-linking of the two beta strands in the single
chain Arc background accelerated refolding by a factor of 170 into the sub
microsecond time scale. However, the major energetic effect of the disulfide
occurs after the transition state for Arc refolding, slowing unfolding by 200 000
fold.
PMID- 11015233
TI - Biophysical characterization of elongin C from saccharomyces cerevisiae
PMID- 11015232
TI - Reaction of hydrogen peroxide with ferrylhemoglobin: superoxide production and
heme degradation.
AB - The reaction of Fe(II) hemoglobin (Hb) but not Fe(III) hemoglobin (metHb) with
hydrogen peroxide results in degradation of the heme moiety. The observation that
heme degradation was inhibited by compounds, which react with ferrylHb such as
sodium sulfide, and peroxidase substrates (ABTS and o-dianisidine), demonstrates
that ferrylHb formation is required for heme degradation. A reaction involving
hydrogen peroxide and ferrylHb was demonstrated by the finding that heme
degradation was inihibited by the addition of catalase which removed hydrogen
peroxide even after the maximal level of ferrylHb was reached. The reaction of
hydrogen peroxide with ferrylHb to produce heme degradation products was shown by
electron paramagnetic resonance to involve the one-electron oxidation of hydrogen
peroxide to the oxygen free radical, superoxide. The inhibition by sodium sulfide
of both superoxide production and the formation of fluorescent heme degradation
products links superoxide production with heme degradation. The inability to
produce heme degradation products by the reaction of metHb with hydrogen peroxide
was explained by the fact that hydrogen peroxide reacting with oxoferrylHb
undergoes a two-electron oxidation, producing oxygen instead of superoxide. This
reaction does not produce heme degradation, but is responsible for the catalytic
removal of hydrogen peroxide. The rapid consumption of hydrogen peroxide as a
result of the metHb formed as an intermediate during the reaction of reduced
hemoglobin with hydrogen peroxide was shown to limit the extent of heme
degradation.
PMID- 11015235
TI - Detection of circulating lipopolysaccharide-bound monocytes in children with gram
negative sepsis.
AB - The possibility that gram-negative sepsis can be diagnosed by detection of
lipopolysaccharide (LPS) bound on the surface of monocytes in the circulation of
patients with gram-negative sepsis was investigated. Peripheral monocytes were
analyzed by flow cytometer and an anti-LPS monoclonal antibody in 3 groups:
children with gram-negative sepsis, children with gram-positive sepsis, and
healthy children. LPS-bound monocytes were found in all patients with gram
negative sepsis but not in children with gram-positive sepsis or in healthy
children. Therefore, the flow cytometry method developed for this study may be a
novel method for diagnosing gram-negative sepsis.
PMID- 11015234
TI - Human immune response to streptococcal inhibitor of complement, a serotype M1
group A Streptococcus extracellular protein involved in epidemics.
AB - Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular
protein made by serotype M1 group A Streptococcus strains that contributes to
bacterial persistence in the mammalian upper respiratory tract. New variants of
the Sic protein arise very rapidly by positive selection in human populations
during M1 epidemics. The human antibody response to Sic was analyzed. Of 636
persons living in diverse localities, 43% had anti-Sic serum antibodies, but only
16.4% had anti-M1 protein serum antibody. Anti-Sic antibody was also present in
nasal wash specimens in high frequency. Linear B cell epitope mapping showed that
serum antibodies recognized epitopes located in structurally variable regions of
Sic and the amino terminal hypervariable region of the M1 protein. Phage display
analyses confirmed that the polymorphic regions of Sic are primary targets of
host antibodies. These results support the hypothesis that selection of Sic
variants occurs on mucosal surfaces by a mechanism that involves acquired host
antibody.
PMID- 11015236
TI - Inverse relationship between gastric colonization of Helicobacter pylori and
diarrheal illnesses in children: results of a population-based cross-sectional
study.
AB - It has been suggested that carriage of Helicobacter pylori may protect against
infections by exogenous intestinal pathogens. An analysis was done of all
children who were screened for school fitness during 1996-1998 in Ulm, Germany,
to compare rates of diarrheal illnesses in H. pylori-positive and H. pylori
negative children. Of 2477 5-8-year-old children studied, 304 (12.3%) were H.
pylori-positive by carbon 13-labeled urea breath test. For H. pylori-positive
children, diarrhea within the prior 3 months was less often reported than for H.
pylori-negative children (54.3% vs. 76.1%; P<.001, adjusted for nationality).
Compared with H. pylori-negative children, the odds ratio (OR) for the occurrence
of diarrhea within the prior 3 months was 0.37 (95% confidence interval [CI],
0.28-0.49) for H. pylori-positive children; after adjustment for covariates, the
OR was 0.56 (95% CI, 0.42-0.76). These data support the hypothesis that H. pylori
colonization may protect against diarrheagenic gastrointestinal infections.
PMID- 11015237
TI - Two-thumb vs. two-finger chest compression in an infant model of prolonged
cardiopulmonary resuscitation.
AB - OBJECTIVE: Previous experiments in the authors' swine lab have shown that
cardiopulmonary resuscitation (CPR) using two-thumb chest compression with a
thoracic squeeze (TT) produces higher blood and perfusion pressures when compared
with the American Heart Association (AHA)-recommended two-finger (TF) technique.
Previous studies were of short duration (1-2 minutes). The hypothesis was that TT
would be superior to TF during prolonged CPR in an infant model. METHODS: This
was a prospective, randomized crossover experiment in a laboratory setting.
Twenty-one AHA-certified rescuers performed basic CPR for two 10-minute periods,
one with TT and the other with TF. Trials were separated by 2-14 days, and the
order was randomly assigned. The experimental circuit consisted of a modified
manikin with a fixed-volume arterial system attached to a neonatal monitor via an
arterial pressure transducer. The arterial circuit was composed of a 50-mL bag of
normal saline solution (air removed) attached to the manikin chest plate and
connected to the transducer with a 20-gauge intravenous catheter and tubing.
Rescuers were blinded to the arterial pressure tracing. Systolic blood pressure
(SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were
recorded in mm Hg, and pulse pressures (PPs) were calculated. Data were analyzed
with two-way repeated-measures analysis of variance. Sphericity assumed modeling,
with Greenhouse-Geisser and Huynh-Feldt adjustments, was applied. RESULTS:
Marginal means for TT SBP (68.9), DBP (17.6), MAP (35.3), and PP (51.4) were
higher than for TF SBP (44.8), DBP (12.5), MAP (23.3), and PP (32.2). All four
pressures were significantly different between the two techniques (p< or =0.001).
CONCLUSION: In this infant CPR model, TT chest compression produced higher MAP,
SBP, DBP, and PP when compared with TF chest compression during a clinically
relevant duration of prolonged CPR.
PMID- 11015238
TI - Development of a histomorphologic scale to quantify cutaneous scars after burns.
AB - OBJECTIVE: Cutaneous wound healing in adults invariably results in scarring;
however, there are few scales to quantify the degree of such scarring. The
authors developed a histomorphologic scale for quantifying scarring after
cutaneous burn injury. METHODS: As part of a randomized trial comparing a variety
of burn therapies, 40 partial-thickness burns were created on the backs and
flanks of anesthetized pigs and treated with a tissue adhesive, antibiotic
ointment, occlusive dressing, or dry gauze. Gross scar appearance was
independently assessed by two investigators at 90 days on a 100-mm visual analog
scale (VAS) marked "best appearance" at the high end. One of the investigators
repeated the observation 30 days later. Full-thickness biopsies were taken 90
days after injury and evaluated histologically by a dermatopathologist for the
presence of hyperkeratosis, epidermal hyperplasia, presence and depth of scar
(defined as abnormally oriented collagen under polarized light), fibroplasia,
vascular proliferation, and absence of adnexa, including hair follicles, apocrine
glands, and smooth muscles. One point was assigned for each category in the
presence of a normal finding, whereas an abnormal finding was assigned a score of
zero. The normal dermis (absence of abnormal collagen) was given a score of 3,
while decreasing scores of 2 to 0 were given for progressively deeper scars
(i.e., 2 for papillary dermis, 1 for upper half of reticular dermis, and 0 for
deep dermal lower half). The total histomorphologic score was derived by adding
the scores on the individual items. The score ranges from 0 to 10 from worst
scarring to absence of scarring, respectively. A subset of observations was
evaluated a second time by one of the observers one month later. Intraobserver
reliability of the histomorphologic scale was assessed with Spearman's
correlation. Inter- and intraobserver Pearson's correlations for the gross scar
VAS were calculated, and the correlation between gross and histomorphologic
scores was assessed. RESULTS: Intraobserver correlation for individual
histomorphologic categories ranged from 0.19 to 1.00. Intraobserver correlation
for the total histologic score was 0.95. Inter- and intraobserver correlations
for the gross scar VAS were 0.8 each. Correlation between the histomorphologic
scale and the gross scar VAS was 0.38. CONCLUSIONS: A new reliable
histomorphologic method for quantifying and scoring cutaneous scars is described
together with a reliable scar VAS. However, these two scales are not highly
correlated.
PMID- 11015239
TI - Calcium and digoxin vs. calcium alone for severe verapamil toxicity.
AB - Calcium chloride (CaCl(2)) is ineffective in severe calcium channel antagonist
overdoses. Digoxin increases intracellular calcium by inhibiting the sodium
potassium adenosine triphosphatase enzymes. OBJECTIVE: To examine the effect of
calcium and digoxin on the treatment of verapamil toxicity. METHODS: Sixteen dogs
were instrumented to monitor hemodynamics. Verapamil toxicity (50% decrease in
mean arterial pressure) was induced with verapamil (VER) at 6 mg/kg/hr and
maintained for 30 minutes by titrating the VER rate. Following toxicity, the dogs
received either digoxin (0.018 mg/kg) (DIG) (n = 8) or saline (No-DIG) (n = 8).
Both groups received VER at three sequential rates (1 mg/kg/hr from 0 to 90 min,
6 mg/kg/hr from 90 to 130 min, and 18 mg/kg/hr from 130 to 170 min). Calcium
boluses were given (500 mg at 0 and 15 min; 1 g at 140, 150, and 160 min). Data
were analyzed using a repeated-measures analysis of covariance comparing DIG vs
No-DIG across the infusion rates and time. Animal weight, does of VER
administered during the toxicity phase, and baseline values were included as
covariates. Mortality rates were compared at 230 minutes following a total dose
of 500 mg of VER. RESULTS: The DIG group had a higher systolic blood pressure
(SBP) than the No-DIG group during the 1-mg/kg/hr (early p = 0.028, late p =
0.01), 6-mg/kg/hr (p = 0.051), and 18-mg/kg/hr (p = 0.038) VER infusion rates.
There were no deaths in the DIG group and four deaths in the No-DIG group (Fisher
= 0.08). Neither ventricular tachycardia nor ventricular fibrillation developed
in either group. Other hemodynamic parameters did not show significant changes.
CONCLUSIONS: In a model of severe verapamil toxicity, digoxin plus calcium raised
SBP and did not result in ventricular arrhythmias when compared with calcium
alone.
PMID- 11015240
TI - The efficacy of nebulized racemic epinephrine in children with acute asthma: a
randomized, double-blind trial.
AB - OBJECTIVES: Recent work in bronchiolitis has demonstrated a significant clinical
improvement in children treated with epinephrine over nebulized salbutamol. The
objective of this study was to determine whether nebulized epinephrine, as
compared with nebulized salbutamol, causes a greater clinical improvement in
children with acute asthma. METHODS: Children, aged 1 to 17 years, with acute
asthma presenting to the emergency department (ED) were eligible. In this double
blind study, patients were randomly allocated to receive either salbutamol or
racemic epinephrine by nebulization at 0, 20, and 40 minutes. All patients
received oral steroids. The primary outcome measure was a change in pulmonary
index score (PIS). RESULTS: One hundred twenty patients were randomized. The
groups were comparable in terms of age, gender, asthma severity, previous
treatments, and use of inhaled steroids. There was no significant difference
between treatments in the change in PIS, length of stay, admission to hospital,
or relapse rate. The epinephrine-treated group had significantly more minor side
effects (such as excess or brownish nasal discharge). CONCLUSIONS: There is no
significant clinical benefit of nebulized epinephrine over salbutamol in children
1-17 years old with mild to moderate acute asthma. Salbutamol remains the
treatment of choice in children with known asthma.
PMID- 11015241
TI - Concordance of clinical findings and clinical judgment in the diagnosis of
streptococcal pharyngitis.
AB - OBJECTIVE: It is uncertain how reliably clinicians apply clinical predictors of
group A beta hemolytic streptococcal pharyngitis (GABHSP) to form a clinical
impression, and how reliably this impression predicts culture results. The
objective was to study clinician accuracy in diagnosing GABHSP. METHODS: This was
a prospective cohort study, conducted at an urgent care center of a major
university. A convenience sample of 218 patients, aged 9-83 years, presenting
with sore throat, was enrolled. Symptoms and signs of pharyngitis were documented
on a standardized form; the likelihood of GABHSP was plotted on a visual analog
scale; and throat culture was obtained. A comparison was then made between the
clinical impression on presentation and the throat culture result. RESULTS:
Throat cultures were positive for GABHSP in 41 patients (19%). The probability of
GABHSP was related to node size and tenderness, tonsillar exudate and
hypertrophy, and pharyngeal erythema (p<0.05); but not throat soreness, degree of
fever, or cough. A strong clinical impression of GABHSP (>50% on the visual
analog scale) was associated with tonsillar exudate and hypertrophy, tender
nodes, and pharyngeal erythema. Together, these four predictors had a sensitivity
of 71%, a specificity of 77%, and a positive predictive value of 46%.
CONCLUSIONS: Clinicians in this study based their impression of GABHSP on the
most reliable symptoms and signs. While a strong clinical suspicion of GABHSP
predicted a greater probability of positive culture, the clinicians consistently
overestimated the probability of GABHSP. Symptoms and signs predict GABHSP
unreliably when used alone; they are helpful in modifying estimates of disease
probability to facilitate optimal use of laboratory tests and antibiotics.
PMID- 11015242
TI - Early discharge of patients with presumed opioid overdose: development of a
clinical prediction rule.
AB - OBJECTIVE: To develop a clinical prediction rule to identify patients who can be
safely discharged one hour after the administration of naloxone for presumed
opioid overdose. METHODS: Patients who received naloxone for known or presumed
opioid overdose were formally evaluated one hour later for multiple potential
predictor variables. Patients were classified into two groups: those with adverse
events within 24 hours and those without. Using classification and regression
tree methodology, a decision rule was developed to predict safe discharge.
RESULTS: Clinical findings from 573 patients allowed us to develop a clinical
prediction rule with a sensitivity of 99% (95% CI = 96% to 100%) and a
specificity of 40% (95% CI = 36% to 45%). Patients with presumed opioid overdose
can be safely discharged one hour after naloxone administration if they: 1) can
mobilize as usual; 2) have oxygen saturation on room air of >92%; 3) have a
respiratory rate >10 breaths/min and <20 breaths/min; 4) have a temperature of
>35.0 degrees C and <37.5 degrees C; 5) have a heart rate >50 beats/min and <100
beats/min; and 6) have a Glasgow Coma Scale score of 15. CONCLUSIONS: This
prediction rule for safe early discharge of patients with presumed opioid
overdose performs well in this derivation set but requires validation followed by
confirmation of safe implementation.
PMID- 11015243
TI - Maximizing the sensitivity and specificity of pediatric trauma team activation
criteria.
AB - BACKGROUND: Care of the severely injured child requires the rapid assembly of
personnel trained in pediatric trauma care. Trauma team activation criteria,
which are highly sensitive and maximally specific for identifying the child who
requires resuscitation, are necessary to provide rapid care to all who need it,
while using resources efficiently. OBJECTIVE: To determine the sensitivity and
specificity of the standard trauma team activation (TTA) criteria for identifying
patients who receive resuscitation in the emergency department. METHODS: A one
year study was conducted of all patients transported by emergency medical out-of
hospital services for a trauma-related complaint. For all patients, out-of
hospital medical control operators recorded whether patients met TTA criteria
and, if so, which criteria were met. Criteria included standard physiologic,
anatomic, and mechanism parameters. Sensitivity and specificity for the outcome
of resuscitation (volume restoration, assisted ventilation or intubation, chest
tube insertion/needle decompression, operative intervention) were calculated.
RESULTS: A total of 492 patients met the case definition. Two-thirds were male,
the mean age was 8 years (+/-4.8 SD), and the Injury Severity Score was > or =15
in 9.3%. Trauma team activation criteria were met by 179 patients (36. 4%) and,
of these, 107 met mechanism criteria only. A resuscitative intervention was
received by 54 (10.9%) of the total and none in the mechanism-only group.
Sensitivity and specificity of the TTA criteria for predicting receipt of a
resuscitation procedure were 98. 1% and 71.2%, respectively. When mechanism
criteria were excluded, the sensitivity remained 98.1% and the specificity
increased to 95. 7%. CONCLUSIONS: Criteria for TTA that include patients who meet
mechanism criteria only are not specific for identifying patients who receive a
resuscitative intervention. Use of anatomic and physiologic criteria only results
in an increase in specificity, thereby reducing overtriage while retaining a high
sensitivity.
PMID- 11015244
TI - Conjoint smoking and drinking: a case for dual-substance intervention among young
emergency department patients.
AB - OBJECTIVES: To better understand conjoint smoking and drinking among young adult
emergency department (ED) patients, the purposes of this investigation were: 1)
to assess the prevalence of conjoint use; 2) to determine the factors associated
with conjoint alcohol use and smoking; and 3) to address the implications for
future ED-based investigation of dual-substance intervention. METHODS: Data for
this investigation were obtained from a battery of questionnaires administered to
the routine-care patients during an alcohol screening in the ED, which was part
of a larger alcohol intervention study. RESULTS: Study findings revealed that a
majority of patients with self-reported alcohol-related problems were smokers. In
fact, drinkers who smoked were likely to be pack-a-day smokers. Among the study
sample, being female, having low education levels (e.g., high school education or
less), having some emotional problems, and currently using marijuana were risk
factors for conjoint smoking and drinking. CONCLUSIONS: Conjoint users were
identifiable through brief screening. Given the prevalence of conjoint smoking
and alcohol use among the ED sample and a specific set of risk factors, tailored
intervention for alcohol and nicotine dependence may be an important and
opportunistic clinical ED service.
PMID- 11015245
TI - Emergency medicine resident documentation: results of the 1999 american board of
emergency medicine in-training examination survey.
AB - OBJECTIVES: To assess how emergency medicine (EM) residents perform medical
record documentation, and how well they comply with Health Care Financing
Administration (HCFA) Medicare charting guidelines. In addition, the study
investigated their abilities and confidence with billing and coding of patient
care visits and procedures performed in the emergency department (ED). Finally,
the study assessed their exposure to both online faculty instruction and formal
didactic experience with this component of their curriculum. METHODS: A survey
was conducted consisting of closed-ended questions investigating medical record
documentation in the ED. The survey was distributed to all EM residents, EM
internal medicine, and EM-pediatrics residents taking the 1999 American Board of
Emergency Medicine (ABEM) In-Training examination. Five EM residents and the
Society for Academic Emergency Medicine (SAEM) board of directors prevalidated
the survey. Summary statistics were calculated and resident levels were compared
for each question using either chi-square or Fisher's exact test. Alpha was 0.05
for all comparisons. RESULTS: Completed surveys were returned from 88.5% of the
respondents. A small minority of the residents code their own charts (6%).
Patient encounters are most frequently documented on free-form handwritten charts
(38%), and a total of 76% of the respondents reported using handwritten forms as
a portion of the patient's final chart. Twenty-nine percent reported delays of
more than 30 minutes to access medical record information for a patient evaluated
in their ED within the previous 72 hours. Twenty-five percent "never" record
their supervising faculty's involvement in patient care, and another 25% record
that information "1-25%" of the time. Seventy-nine percent are "never" or
"rarely" requested by their faculty to clarify or add to medical records for
billing purposes. Only 4% of the EM residents were "extremely confident" in their
ability to perform billing and coding, and more than 80% reported not knowing the
physician charges for services or procedures performed in the ED. CONCLUSIONS:
The handwritten chart is the most widely used method of patient care
documentation, either entirely or as a component of a templated chart. Most EM
residents do not document their faculty's participation in the care of patients.
This could lead to overestimation of faculty noncompliance with HCFA billing
guidelines. Emergency medicine residents are not confident in their knowledge of
medical record documentation and coding procedures, nor of charges for services
rendered in the ED.
PMID- 11015246
TI - Clinicopathological conference: sudden-onset facial edema in an autistic child.
PMID- 11015247
TI - Organization of emergency medicine at medical schools: compelling reasons for
departmental status.
PMID- 11015248
TI - Ethics seminars: case studies in "futility"-challenges for academic emergency
medicine.
AB - The concept of "futility" and its determination in emergency medicine pose unique
challenges to emergency physicians, patients, and society. The term "futility,"
although commonly used, is problematic in its scope, meaning, and interpretation.
To bridge this gap in understanding, the authors suggest the construct of
clinically nonbeneficial interventions (CNBI), instead of "futility. " This
language better informs discussions of nonbeneficial interventions across the
risk spectrum of emergency medical practice, while retaining the focus on the
patient's interests. Two cases are presented, which underscore the need for
prudence and empathetic communication when addressing issues of CNBI.
Determinations of expected benefit should be based on established scientific
evidence, and the goals and values of patients, not on individual biases
regarding quality of life or other subjective matters. While physicians are under
no ethical obligation to provide treatments that they judge have no realistic
likelihood of clinical benefit, the context in which these determinations take
place is of critical importance. When certain interventions are appropriately
withheld, concerted efforts should be made to maintain effective communication,
comfort, support, and counseling for patients, friends, and families. In all
aspects of clinical decision making, the value of various interventions and
therapies must be based on expected risks and benefits to the patients, first and
foremost.
PMID- 11015249
TI - Can clinical parameters predict fractures in acute pediatric wrist injuries?
AB - OBJECTIVE: Fractures around the wrist are common in pediatric patients presenting
to the emergency department (ED). This pilot study was aimed at identifying
clinical variables that are most likely to be associated with a fracture.
METHODS: This was a prospective blinded case series of patients 3-18 years of age
presenting with an acute (<3 days) wrist injury, without obvious deformity. A
team of five investigators blinded to the eventual radiographic findings
evaluated patients. Physical examination variables included range of motion
(ROM), site of maximal tenderness, and functional deficit. The latter was
determined objectively, by recording any difference in grip strength between the
injured and noninjured hands. Diagnostic radiographs were obtained for all
patients. Univariate analysis using Wilks' log likelihood ratio test was
performed to identify clinical variables associated with confirmed wrist
fractures. Sample size was determined based on the ability to detect a difference
of 15 degrees in the ROM variables, 20% point differences in grip strength, and
30% proportion differences in categorical variables using a power of 0.8 and a
two-tailed of 0.05. RESULTS: The ROMs were not significantly different between
the fracture (Fx) and nonfracture (NFx) group. There was significant change in
the grip strength between the Fx and NFx groups (t = 3.3, p = 0.0019). Tenderness
over the distal radius was also associated with a greater likelihood of a
fracture (G(2) = 5.0, p = 0.02). Sensitivity of clinical prediction was found to
be 79%, and specificity was 63%. The false-negative rate was 0.21 and the false
positive rate was 0.37, while the positive predictive value was found to be 0.68
and negative predictive value 0.75. CONCLUSIONS: Distal radius point tenderness
and a 20% or more decrease in grip strength were predictive of fractures.
PMID- 11015250
TI - Low plasma thiamine levels in elder patients admitted through the emergency
department.
AB - OBJECTIVES: To determine the prevalence of thiamine deficiency in a high-risk
group of elder emergency department (ED) patients who reside in nursing homes and
need admission to the hospital, and to determine the effect of patients' diets on
this prevalence. METHODS: This was an observational pilot study of 75 consecutive
ED patients aged 65 years or older who lived in a nursing home and were admitted
to the hospital. Plasma thiamine levels were measured by high-pressure liquid
chromatography on serum samples collected within 24 hours of hospital admission.
Nursing home records were reviewed to determine whether patients received
nutritional supplementation or enteral tube feedings. RESULTS: Seventy patients
participated and had a mean plasma thiamine level of 27.3 microg/dL (95% CI =
20.2 to 34.4). Fourteen percent (n = 10, 95% CI = 8% to 24%) were thiamine
deficient (<10 microg/dL). Patients not receiving dietary supplements or tube
feedings (n = 26) had lower mean thiamine levels (20.3 microg/dL, 95% CI = 12.7
to 27.9) and were thiamine-deficient more often (27%) than patients receiving
dietary support (n = 44, 31.5 microg/dL, 95% CI = 24.7 to 38.3, 7% thiamine
deficient). CONCLUSIONS: Elder nursing home patients seen in the ED and admitted
to the hospital are frequently thiamine-deficient. Empiric thiamine
supplementation is often used in the ED for other high-risk patients, such as
alcoholic individuals, and may be appropriate for high-risk elder patients.
Further research is needed to determine whether thiamine supplementation in these
patients can improve their clinical outcomes.
PMID- 11015251
TI - Bilateral tubal ectopic pregnancy: a tale of caution.
AB - Diagnosis of ectopic pregnancy continues to be an important challenge facing
emergency physicians. The authors present a case of bilateral tubal ectopic
pregnancy and discuss its clinical features and diagnostic difficulties. A review
of the English-language literature on the subject is discussed. Suggestions are
made on ways to increase diagnostic accuracy, reduce complications, and preserve
future fertility in this group of patients.
PMID- 11015252
TI - The accuracy of the emergency physician at diagnosing CVA/TIA in the acute care
setting
AB - OBJECTIVE: To determine the accuracy of the ED physician at diagnosing CVA/TIA in
the acute setting. METHODS: We reviewed 246 patients admitted for acute CVA/TIA
during 1997. We reviewed admitting and discharge diagnoses, CT, MRI, and MRA
results. We also reviewed the medical histories of the patients. Patients with
tumors and ICH diagnosed on the initial CT scan were excluded. RESULTS: A total
of 241 patients were included for analysis. Of the patients admitted for CVA, 67%
were discharged with the same diagnosis. Of the patients admitted for TIA, 82%
were discharged with the same diagnosis. 10% of TIAs diagnosed at admission
received the diagnoses at discharge. 22% of CVAs at admission were diagnosed as
TIAs. 11% of CVA/TIAs at admission were given other diagnoses at discharge. Some
of these diagnoses included hemiplegic migraines, Bell's palsy, lumbosacral
spondylosis, giant cell arteritis, basilar artery aneurysm, and viral meningitis.
In considering thrombolysis for CVA, one may then overtreat approximately 30% of
patients and miss approximately 10% of patients who could be candidates for
treatment. The NNT for CVA and thrombolysis is approximately 10. If 30%
overtreatment rate is accurate, then the NNH is approximately 333 assuming an ICH
rate of 1%. For 1,000 patients treated, 100 may benefit (improved function) and 3
would die who did not have the disease. CONCLUSIONS: The accuracy rate of the
diagnosis of CVA at initial presentation is 67%. This is due to many initial
neurologic changes being TIAs and some other diagnoses which can mask as CVA.
Choosing thrombolysis for CVA treatment will involve treatment of many patients
who do not have disease.
PMID- 11015253
TI - EMS transports for difficulty breathing: is there a potential role for CPAP in
the prehospital setting?
AB - Mask-applied continuous positive airway pressure (CPAP) has been shown to reduce
morbidity among patients with acute respiratory distress in the setting of
cardiogenic pulmonary edema. OBJECTIVE: To determine a minimum percentage of
patients transported by ALS for difficulty breathing who could potentially
benefit from a pre-hospital trial of CPAP. METHODS: Paramedic run sheets were
collected from consecutive, adult, ALS transports for a chief complaint of
difficulty breathing over a 6 week period in a large urban EMS system.
Demographic information, medical history, vital signs, clinical assessments, and
transport times were abstracted into a database by trained reviewers. Strict
criteria for CPAP were defined in advance as "acute respiratory distress,"
meaning (1) respiratory rate > 25 and (2) labored or shallow breathing, and
"presumed cardiogenic pulmonary edema," meaning (3) a prior history of heart
disease and (4) presence of bilateral rales on exam. RESULTS: Data from 240
consecutive run sheets were compiled. Median patient age was 66 years old, with
females outnumbering males 168 to 81. A total of 15 spontaneously breathing
patients met all 4 criteria for CPAP. Four of these patients were either
hypotensive (SBP < 90) or had potential for airway compromise (i.e.,
obtundation), making CPAP inadvisable. Among the 11 remaining patients (4.4% of
all transports for difficult breathing), median transport time was 20 minutes
(range 14-31 minutes). CONCLUSIONS: Using very strict criteria, a small but not
significant percentage of patients are optimal candidates for a prehospital trial
of CPAP. Transport times would appear to justify this type of intervention. A
prospective study is currently under way to test the feasibility of administering
CPAP to such patients in the prehospital setting.
PMID- 11015254
TI - Etomidate-facilitated hip reduction in the emergency department
AB - OBJECTIVE: The authors report what they believe is the first reported use of
etomidate to assist in the reduction of a major joint in an outpatient setting.
METHODS: The authors review the case of an elderly woman with a total hip
arthroplasty who experienced four spontaneous posterior hip dislocations in a 5
month period. Etomidate was successfully used in two dislocations where previous
methods had failed. RESULTS: A 68-year-old woman, who 13 months earlier had an
uncomplicated total left hip replacement, was transported to the same ED on four
separate occasions for a spontaneous left hip dislocation. Radiographs in each
instance were significant only for a posterior dislocation of the implant
articulation. The first reduction in the ED was unsuccessful and required a
closed reduction in the operating theater. Seventy-two hours later the second
dislocation and subsequent reduction occurred in the ED using etomidate to
facilitate muscle relaxation. The patient was subsequently discharged home.
Similar scenarios were replayed in the next few months. CONCLUSIONS: Muscle
relaxation is the key characteristic for the reduction of dislocated major
joints. The risks of respiratory depression and hemodynamic alterations with
sedation are not insignificant, especially at the extremes of age. In the present
case, intravenous narcotics and sedative-amnestic agents did not result in
sufficient muscle relaxation. Larger or repeated doses may have resulted in
undesirable or dangerous side effects. Etomidate is a useful adjunct when
cardiopulmonary disease is present. The rapid onset and recovery from etomidate
make it an excellent choice for facilitating the reduction of hip dislocations in
elderly patients with prior total hip replacements.
PMID- 11015255
TI - Antioxidant treatment improves bioenergetics following Ischemia/Reperfusion
AB - Published in: Acad Emerg Med. 2000; 7: 507-8.
PMID- 11015257
TI - Accuracy of interqual criteria in determining the hospitalization need in
medicare patients with gastrointestinal bleeding
AB - Published in: Acad Emerg Med. 2000; 7: 552-3.
PMID- 11015256
TI - Trauma in the very elderly: A community-based study of outcomes at trauma and non
trauma centers
AB - Published in: Acad Emerg Med. 2000; 7: 568.
PMID- 11015258
TI - Retrospective evaluation of potential medicare admission denials using interqual
and millman and roberts admission criteria
AB - Published in: Acad Emerg Med. 2000; 7: 543.
PMID- 11015259
TI - Prevalence and documentation of impaired mental status in elderly emergency
department patients
AB - OBJECTIVE: To determine the prevalence and assess documentation by emergency
department (ED) physicians (EPs) of impaired mental status in elderly ED
patients. METHODS: Cross-sectional, observational study. Subjects: convenience
sampling of ED patients greater than or equal to 70 years of age. Patients were
screened for cognitive impairment with the Orientation Memory Concentration exam
(OMC), and for delirium with the Confusion. Assessment Method screening tool
(CAM). A positive OMC or CAM was considered indicative of impaired mental status.
Patients with delirium were excluded from the cognitive impairment screen. EPs
were blinded to screening results. Physician documentation, dispositions, and
referrals were abstracted from chart review. Proportions and 95% confidence
intervals (CIs) are reported. RESULTS: 180 patients were screened. 46 patients
(26%; 95% CI = 19% to 32%) had impaired mental status. 22 of these (12%; 95% CI =
7% to 17%) had delirium, and 24 (13%; 95% CI = 8% to 18%) had moderate to severe
cognitive impairment. Of all patients with impaired mental status, only 14 (30%;
95% CI = 18% to 46%) had documentation of any impairment by the EP (10 with
delirium (46%; 95% CI = 24% to 68%), and 5 with cognitive impairment (21%; 95% CI
= 7% to 42%). 7 of 22 (32%; 95% CI = 14% to 55%) patients with delirium were
discharged home. Only 2 of 16 patients with impaired mental status (12.5%) were
discharged home with plans noted to address the impairment. CONCLUSIONS:
Impairment in mental status is highly prevalent among older ED patients. Lack of
documentation and referrals by EPs suggests lack of recognition of these
problems. Further education of physicians is needed to improve care in these
areas.
PMID- 11015260
TI - Case finding of At-risk elders in the emergency department (ED): A multicenter
study
AB - Published in: Acad Emerg Med. 2000; 7: 563-4.
PMID- 11015261
TI - Emergency medicine residencies: A descriptive study of program structure
AB - The steady growth in EM residency programs reflects the desirability of EM as a
specialty area for training. However, a profile of programs offered nationwide is
not available. OBJECTIVE: To characterize emergency medicine (EM) programs
nationwide according to program format, curriculum, and opportunities for
subspecialty training. METHODS: In this descriptive study, U.S. emergency
medicine residency curriculums were evaluated electronically using SAEM and
FRIEDA residency information websites. Data collected included program format,
hospital size and volume, rotation durations, curriculum and electives offered.
RESULTS: The most common format (72%, n = 87) is PGY 1, 2, 3 and PGY 2, 3, 4
accounted for 18% (n = 22) and PGY 1, 2, 3, 4 for 10% (n = 12). The average
length of training in the ED is 19 months (range 7-40). Average general pediatric
training is 1.8 months (range 0-5). The average number of rotations outside the
primary site is 4.9 (range 0-19) and elective rotation time and topics varied
considerably. Opportunities for air medical training differed by program format
(82% of PGY 1-3, 79% of PGY 1-4, 75% of PGY 2-4) (table 11-1). CONCLUSIONS: There
is substantial variation in curriculum, in subspecialty exposure, and in
opportunity for electives for residents depending on program format and location.
PMID- 11015262
TI - A critical examination of the USMLE II: does a study month improve test
performance?
AB - Students often are encouraged to elect a study month prior to taking the USMLE
II. OBJECTIVE: To determine if a study month prior to the September USMLE II
improves student test performance. METHODS: Student clerkship sequence was
prospectively recorded for each senior at a large midwestern medical school
during the 1998-99 academic year, and USMLE I and II scores were obtained. USMLE
II scores were compared between students who elected a study month prior to the
September testing date versus those who elected clerkships, while controlling for
USMLE I test scores using multiple linear regression. RESULTS: Complete data were
obtained for 167 senior year medical students. 124 (74.3%) students took the
September USMLE II after electing a study month, and 43 (25.7%) students took the
September USMLE II after electing clerkships. The mean score for those who
elected a study month before the USMLE II test was higher than those electing
clerkships (210.56 +/- 17.12 vs 208.65 +/- 20.83). However, after controlling for
USMLE I scores (r(2) = 0.53; p < 0.01), the election of a study month prior to
the September USMLE II was not associated with an increase in student performance
(r(2) < 0.01; p = 0.73). CONCLUSIONS: These results do not support study months
as a means to improve USMLE II test performance, and suggest that rotations may
be equally beneficial.
PMID- 11015263
TI - Inhaled furosemide in the treatment of acute exacerbations of asthma
AB - Inhalation of the loop diuretic furosemide has been found to protect against
challenges with bronchoconstrictive agents. OBJECTIVE: To determine if furosemide
has any objective and/or subjective therapeutic effect on adult patients with
acute exacerbations of asthma, above and beyond the effects of B2 agonists and
oral glucocorticoids. METHODS: 35 adult patients with acute exacerbations of
asthma were randomized and recruited into the study if they had a prior history
of asthma, and <10 pack-year smoking history, had not received pre-hospital B2
agonists, were not pregnant, and had no sulfonamide allergy. A double blind study
design was employed. One group received albuterol 5 mg with placebo and one group
received albuterol 5 mg with furosemide 40 mg in their nebulizer. Both groups
received prednisone 80 mg po. PEFRs were obtained before initiation of treatment
and 30 and 60 minutes thereafter. A 10 point dyspnea scale was also employed at
initiation of treatment and 30 and 60 minutes thereafter. Physicians were
permitted to give rescue albuterol treatments as deemed necessary. RESULTS: There
was no difference in the treatment arms with respect to PEFR, dyspnea score, or
number of rescue albuterol treatments at 30 and 60 minutes. CONCLUSIONS: We found
no statistical benefit to adding furosemide to a regimen consisting of prednisone
and optimal doses of B2 agonist. We conclude that there is not a current role for
furosemide in acute exacerbations of asthma.
PMID- 11015264
TI - Changes in stroke index measured by impedance cardiography in a human model of
moderate acute blood loss
AB - Early detection of acute hemorrhage is problematic because changes in traditional
parameters such as heart rate and blood pressure are notoriously unreliable.
OBJECTIVE: To observe the effect of acute, moderate blood loss on stroke index
(SI) as measured non-invasively by impedance cardiography. METHODS: Five healthy,
adult volunteers were phlebotomized 590 mL over ten minutes. The volume of blood
loss was expressed as a percent of estimated total blood volume (TBV) according
to the formula TBV = (weight in kg) x (70 mL/kg). Stroke index was measured in a
fixed, reclining position before (SI #1) and after (SI #2) phlebotomy, using the
BioZ.com (Cardiodynamics International Corporation, San Diego, CA) thoracic
bioimpedance monitor. Absolute and relative changes were calculated. RESULTS: In
each volunteer, a fall in SI was noted after phlebotomy. The percent change in SI
ranged from 8% to 18% (table 15-1). There appeared to be a correlation between
blood loss as a percent of estimated total blood volume and the percent decline
in SI among these volunteers. CONCLUSIONS: Impedance cardiography reliably
detected moderate acute blood loss in this small set of healthy, adult
volunteers. If these results can be quantified and validated prospectively in a
larger population, SI may prove to be a valuable, non-invasive parameter for
detection of early hemorrhage shock.
PMID- 11015265
TI - Compliance with emergency department prior authorization requirements under
EMTALA
AB - Published in: Ann Emerg Med. 1999; 34(4 pt 2):S70.
PMID- 11015266
TI - The role of taurine for cellular volume regulation of the hippocampus
AB - Taurine is used for volume regulation in a number of cultured cells, including
neurons and glia. OBJECTIVE: To evaluate the role of this amino acid in brain
volume regulation in situ. METHODS: Hippocampi of adult Sprague-Dawley rats were
cut into 400 &mgr;m slices and equilibrated for 2 hr at room temperature in
artificial cerebrospinal fluid (aCSF) bubbled with 95% O(2)/5% CO(2). Slices then
were perfused with aCSF at 36 degrees C and optically imaged. After 1 hr in
isotonic aCSF (290 mOsm), slices were perfused with hypoosmotic aCSF (200 mOsm)
made by reducing the concentration of NaCl. Images of transmitted light intensity
were captured every 60 sec to assess intracellular volume. For some slices, 1 mM
taurine was added to aCSF during room temperature equilibration and during the
first 30 min at 36 degrees C to replace that lost during slice preparation.
Taurine contents were measured in perchlorate extracts by HPLC. Data were
analyzed by Student's t-tests. RESULTS: Taurine contents of slices incubated in
isotonic aCSF with and without taurine were 97 +/- 1 and 26 +/- 2 nmol/(mg
protein), respectively. The intensity of transmitted light through the CA1 region
increased similarly during the first 20 min in hypoosmotic aCSF, regardless of
taurine treatment. However, after 60 min of hypoosmotic exposure, light
transmittance recovered more in taurine-treated slices (44 +/- 6%) than in
untreated slices (28 +/- 3%, p <0.05). The hypoosmotic-induced transmittance
increase was smaller in the CA3 region for both groups of slices; however,
similar effects of taurine treatment were obtained for subsequent transmittance
recovery. CONCLUSIONS: Sufficient levels of taurine are required for effective
volume regulation of hippocampal slices.
PMID- 11015267
TI - Comparison of two intraosseous infusion techniques in an EMT training program
AB - OBJECTIVE: To compare placement of IO lines using a traditional method with
placement using a new device called the bone injection gun (BIG). METHODS: A
prospective cross-over study was conducted to compare the time to line placement
and ease of insertion for both traditional (Jamshidi) and BIG methods. EMT-P
students and practicing paramedics provided information about their previous
experience with IO line placement. They were assigned to establish an IO line in
a pediatric leg mannequin using each technique, and rated the ease-of-use of each
method. RESULTS: Thirty-eight participants (28 EMT-P students and 10 paramedics)
completed both of the IO skills. Only two (5%) had ever placed an IO line in a
patient previously. Time to placement of the IO device was faster in the BIG
group (16.91 sec. vs. 11.93 sec., p = 0.02). There was no statistical difference
in ease-of-use ratings between the methods (p = 0.816). Student times for
establishing the IO line with the BIG device were faster than the times of the
practicing paramedics (11. 18 sec. vs. 16.25 sec., p = 0.049). CONCLUSIONS: In
the education setting, times to establishment of an IO line were similar using
both the traditional method of insertion and the BIG device. Ratings of both the
students and paramedics were similar with respect to each-of-use for both the
methods.
PMID- 11015268
TI - Weight of backpacks carried by elementary school children: students or sherpas?
AB - Published in: Acad Emerg Med. 2000; 7: 487.
PMID- 11015269
TI - An assessment of quality control testing in an emergency department (ED)
maintained arterial blood gas analyzer
AB - Emergency medicine by its nature requires the immediacy of laboratory testing.
Point of care testing (POCT) affords the ED the fastest access to important
laboratory data. To the best of the authors' knowledge, maintenance of an
arterial blood gas (ABG) analyzer as a POCT device by ED personnel has not been
studied. OBJECTIVE: To determine the accuracy of POCT quality control testing of
an ED maintained ABG Analyzer (Gem Premier)-Instrumentation Laboratory). METHODS:
We compared comprehensive quality control data obtained when the ABG analyzer was
maintained by the Department of Clinical Laboratories with data obtained from the
same analyzer when it was maintained by ED attending physicians. Each parameter
measured by the ABG analyzer was tested using unknown control samples supplied by
the College of American Pathologists. These two groups of data were then compared
to the total number of obtained values submitted to the College of American
Pathologists. RESULTS: Each parameter measured (n = 7) showed no difference
between the two groups in regard to overall pass rate. All values for the two
groups fell within the limits of acceptability when compared to all other samples
analyzed by the College of American Pathologists (range 159-208 other labs).
CONCLUSIONS: ED attendings are capable of quality control maintenance of an ABG
analyzer as a POCT device under the quality control testing parameters set forth
by the College of American Pathologists.
PMID- 11015270
TI - Diagnostic odor recognition
AB - Many diseases, toxic ingestions, and intoxications have characteristic odors.
These odors may provide diagnostic clues that affect rapid treatment long before
laboratory confirmation or clinical deterioration. Odor recognition skills,
similar to auscultation and palpation skills, require teaching and practical
exposure. Dr. Goldfrank and colleagues recognized the importance of teaching odor
recognition to emergency service providers. They proposed the "sniffing bar"
method for odor recognition training. OBJECTIVES: (1) To identify the recognition
rates of medically important odors among emergency care providers. (2) To
investigate the effectiveness of teaching odor recognition. Hypothesis: The
recognition rates of medically important odors will increase after teaching
exposure. METHODS: The study exposed emergency care providers to 11 tubes of
odors. Identifications of each substance were recorded. After corrective
feedback, subjects were re-tested on their ability to identify the odors.
Analysis of odor recognition improvement after teaching was done via chi-square
test. RESULTS: Improvement in identification after teaching was seen in all
odors. However, the improvement was significant only in the lesscommon substances
because their initial recognition was especially low. Significant changes may
improve with a larger sample size. Subjects often confuse the odors of alcohol
with acetone, and wintergreen with camphor. CONCLUSIONS: The recognition rates
are higher for the more-common odors, and lower for the less-common odors.
Teaching exposures to the less well-known odors are effective and can
significantly improve the recognition rate of these substances. Because odor
recognition may affect rapid diagnosis and treatment of certain medical
emergencies such as toxic ingestion, future studies should investigate the
correlation between odor recognition and the ability to identify corresponding
medical emergencies.
PMID- 11015271
TI - Physiological manifestations of systemic activation of complement
AB - Published in: Acad Emerg Med. 2000; 7: 558.
PMID- 11015272
TI - Shaken. Not stirred-temperature change and heat loss during delivery of IV fluids
AB - Microwave-heated intravenous fluids are used in the rewarming of hypothermic
patients. OBJECTIVES: To study the effect of both shaking of the microwaved bag
and heat loss during delivery. METHODS: Twenty 1-liter normal saline bags were
heated individually in a commercial microwave, immediately randomized into a
"shaken" or a "non-shaken" group. The temperature of the fluid was recorded
initially out of the bag and then at one-minute intervals by a blinded observer
as the fluid ran "wideopen" through ambient temperature tubing. RESULTS: No
statistically significant temperature difference occurred in any of the measured
time intervals between the shaken and the non-shaken bags. Seventy percent of the
overall temperature losses occurred in the first three minutes out of the
microwave for both groups. CONCLUSIONS: Absence of shaking of the microwaved
fluids does not produce "hot spots." Higher initial temperatures out of the bag
should be considered as well as warming of the IV tubing.
PMID- 11015273
TI - The effect of carbonated beverages on colorimetric end-tidal CO(2) determination
AB - Esophageal intubation is a significant complication of attempted airway control.
Colorimetric end-tidal CO(2) monitors are highly sensitive and specific for
detecting the presence of CO(2). There are reports of false-positive end-tidal
CO(2) readings from esophageal intubations in patients who had ingested
carbonated beverages. OBJECTIVE: To determine whether carbonated gastric contents
can affect colorimetric end-tidal CO(2) readings. METHODS: End-tidal CO(2) was
measured in sacrificed piglets at measured time intervals after instillation of 5
, 10-, 15-, and 20-mL aliquots of Diet Coke were placed into the stomach via a 28
French orogastric tube followed by esophageal intubation. The stomach was
completely evacuated prior to each instillation and rechecked for baseline CO(2).
RESULTS: Compiled data from three piglets (20-30 kg). Piglets were not ventilated
or moved and determinations were measured at 20 degrees while supine. All data
collected within 2 hours postmortem (table 24-1). CONCLUSIONS: The colorimetric
end-tidal CO(2) turned "yellow" and did not change to blue with extended
insufflations. The CO(2) of a small quantity of carbonated beverage in the
stomach could be "blown off" by multiple insufflations. We conclude that
esophageal intubation in the setting of recent ingestion of a carbonated beverage
may result in a false-positive end-tidal CO(2) determination.
PMID- 11015275
TI - Efficacy of the porcine model for demonstrating pericardial effusion with real
time ultrasound
AB - Ultrasound in emergency medicine (EM) is an invaluable tool for emergent
evaluation of pericardial effusion and tamponade. The training in the recognition
of such has relied on ultrasonic images or videotapes. OBJECTIVE: To evaluate the
efficacy of demonstrating pericardial effusion and tamponade using real-time
ultrasound. METHODS: A convenience sample of 10 Yorkshire swine were
anesthetized, sedated, intubated, and monitored as per an approved EM training
protocol. Using EKG guidance and a subxiphoid approach, an 18-gauge spinal needle
was advanced into the pericardium until a current of injury was detected. After a
slight withdrawal of the needle, an aliquot of 50-100 mL of normal saline was
instilled to produce a pericardial effusion. Ultrasound was used before and after
the instillation of fluid into the pericardium. The effusion was confirmed by
subsequent pericardiocentesis or by visual inspection on thoracotomy. RESULTS:
The instillation saline, detection of effusion, and subsequent confirmation by
ultrasound, pericardiocentesis, or visual inspection were successfully performed
in 10/10 pigs. Under ultrasound, one pig had a preexisting effusion. Another had
much less fluid visualized. On thoracotomy, the saline was found to have leaked
into the adjacent lung parenchyma. CONCLUSIONS: We conclude that the porcine
model is an adequate model to demonstrate pericardial effusion using real-time
ultrasound.
PMID- 11015274
TI - Ultrasonography evaluation of retrobulbar hematoma in bovine orbits
AB - As the proptotic eye is pushed anteriorly against the canthis, pressure within
the eye increases until there is inadequate perfusion of the eye due to the
pressure effects. computed tomography (CT) scan of the orbit is the most common
method of diagnosing a retrobulbar hematoma. In the trauma/emergency department
setting, where the wait for a CT scan may present significant delay, bedside
ultrasonography may aid in the rapid diagnosis and treatment of a retrobulbar
hematoma. OBJECTIVE: To establish concordance between orbital CT scan and a
bedside sonographic orbital evaluation of a retrobulbar hematoma. METHODS:
Eighteen of 22 bovine orbits were injected with a 10-mL mixture of calcium
treated banked blood and contrast into the retro-orbital space thereby effecting
a retrobulbar hematoma. Each orbit was studied with CT and evaluated by a
neuroradiologist. Four orbits were left intact as controls. Each orbit underwent
an ultrasonographic evaluation. The ultrasonographer was first allowed to study
an orbit with a documented hematoma and a control. Thereafter, he was blinded to
the orbits containing hematoma, did not physically examine each orbit, and
completed each exam in a darkened room. The CT results were correlated with the
ultrasound findings. RESULTS: 15 of 18 orbits (83%) were correctly identified as
containing hematoma by ultrasound. All four intact orbits were correctly
identified as being free of hematoma (kappa 0.6). CONCLUSIONS: Bedside
ultrasonography may aid in the rapid diagnosis of a retrobulbar hematoma.
PMID- 11015276
TI - Blood cultures in pyelonephritis: Do results change therapy?
AB - OBJECTIVE: To determine how often blood culture results are instrumental in
directing the therapy of patients with pyelonephritis. METHODS: Retrospective
chart review of all patients admitted to Doctors Hospital with a diagnosis of
pyelonephritis to ascertain whether the results of blood cultures were
instrumental in the management of those patients. For study purposes, results of
blood cultures were considered instrumental if the treatment regimen or
diagnostic procedures were changed because of those results. RESULTS: 212
patients were admitted during the study period with a diagnosis of
pyelonephritis. Of these, 105 (49.5%) had blood cultures ordered as part of their
workup. Adult patients had at least 2 blood cultures ordered and some had as many
as 4 or 6 sets ordered during hospitalization. Most pediatric patients had only a
single blood culture ordered for diagnosis. Of the 105 patients, 88 (83.5%) had
no growth on any of the tubes drawn. 17 patients had positive growth in at least
one tube; however, 6 out of these 17 patients were judged by the treating
physician to have contaminated cultures that were not diagnostically useful. Of
the 105 patients, only 11 (10.4%) were considered to have positive culture
results by their treating physician. The organism identified by blood culture was
compared to that present in the patient's urine culture, and in only 2 patients
did the results differ and were found to have a secondary site of infection. Only
in these 2 cases were the antibiotic regimens changed because of the blood
culture results. No patient without a second site of infection had a change in
therapy based on the blood culture results. CONCLUSIONS: In patients admitted for
pyelonephritis, blood cultures may not be needed.
PMID- 11015277
TI - The incidence of positive cultures in women suspected of having PID/Salpingitis
AB - OBJECTIVES: To determine the incidence of GC and chlamydia in women with
suspected acute pelvic inflammatory disease. A secondary objective was to
investigate the clinical usefulness of physical exam findings of vaginal
discharge, cervical motion, and adnexal tenderness. METHODS: This was a
retrospective chart review of patients seen in the ED. Patients were entered into
the study if they had PID/salpingitis as their discharge diagnosis and cultures
performed for GC and chlamydia. RESULTS: A total of 133 charts were reviewed. 13
patients were excluded due to incomplete charting of history and physical exam or
inability to obtain culture results. Of the remaining 120 patients, 70 cultures
were negative for any growth. 10 cultures were positive for GC and 10 cultures
were positive for chlamydia. In reviewing the physical exam findings in women
with negative cultures, 74% had discharge, 93% had cmt, and 66% had adnexal
tenderness. For women with cultures positive for GC and chlamydia, 90% had
discharge, 80% had cmt, and 75% had adnexal tenderness. For vaginal discharge the
sens, spec, ppv, npv were 0.90, 0.26, 0.35, 0.90. For cmt the sens, spec, ppv,
npv were 0.80, 0.07, 0.20, 0.55. For adnexal tenderness the sens, spec, ppv, npv
were 0. 75, 0.34, 0.25, 0.83. No combination of the three physical exam findings
increased the ppv. CONCLUSIONS: The incidence of positive cultures in women
suspected of having PID/salpingitis is 16%. The physical exam findings were not
predictive of disease secondary to the high number of false positives. Although
16% positives may warrant empiric treatment, patients should not be told they
have PID/salpingitis until the cultures are available.
PMID- 11015278
TI - Emergency medicine residency director perceptions of the resident selection
process
AB - OBJECTIVE: To assess perceptions of emergency medicine (EM) program directors
(PDs) of the resident selection process. METHODS: PDs of 120 EM residencies were
mailed a 22 question survey immediately following the 1999 match. (Applicants
interviewing in more than one specialty and post-interview communications were
areas of interest). Non-respondents received a second mailing. RESULTS: Ninety
eight (81. 7%) completed surveys were returned. Five PDs felt that interviewing
in more than one specialty was ethically wrong, while most felt multi-specialty
interviews were a system byproduct (42%) or that there was nothing wrong (41%).
Eighty-one percent of PDs felt the applicant's rank order would be negatively
affected if the applicant disclosed interviewing in >1 specialty. Forty-seven
percent of PDs (always or frequently) told applicants to keep in touch if
interested in the program. However, 88% of PDs were skeptical or did not believe
an applicant's communicated intent to rank the program 'high,' nor did this
communication influence an applicant's rank order (75%). Forty-two percent of PDs
reported informal commitments by applicants. PDs frequently felt lied to by
applicants (always (4%), frequently (42%), sometimes (42%)). Applicants often ask
how the program intends to rank them. Highly ranked applicants receive positive
responses from 61% of PDs vs. 33% of PDs who give negative responses to low
ranked applicants. Ten percent of PDs offer residency positions outside of the
match. CONCLUSIONS: Applicants who interview in >1 specialty are viewed
negatively by PDs. Post-interview communications by applicants are viewed with
skepticism. Gamesmanship is practiced commonly during the resident selection
process.
PMID- 11015279
TI - Medical toxicology experience during emergency medicine residency
AB - Medical toxicology (MT) is a core content area of emergency medicine (EM) as well
as an American Board of Medical Specialties recognized subspecialty of EM.
OBJECTIVE: To obtain information concerning MT education in EM residencies.
METHODS: A questionnaire was sent to the director of each EM program in the
Society for Academic Emergency Medicine (SAEM) Residency Catalog. Subsequent
telephone contact was made to encourage participation. Information was obtained
about program format, poison control center (PCC) location, and inclusion of a
toxicologist on faculty as well as specifics about MT rotations and organized
educational activities. RESULTS: Survey participation was 62 of 122 (51%)
programs. A toxicologist is on faculty at 39 (63%) programs and 5 (26%) of the
programs without a toxicologist intend to recruit one in the near future. A MT
rotation is a requirement of 46 (76%), an elective at 12 (19%), and not available
at 3 (5%) programs. The rotation is >/=4 weeks at 46 (78%) of the programs with a
rotation. At 18 (31%), time is spent primarily at the hospital, while at 26 (44%)
it is at the PCC. At 5 (8%) programs, equal/near equal time is spent at the
hospital and PCC. The individual(s) providing resident supervision at PCCs is not
uniform. Organized MT experience other than a rotation is included in 39 (63%) of
programs. CONCLUSIONS: Due to suboptimal participation, many issues regarding MT
education in EM residency remain uncertain. However, some findings are clear.
While most participating programs have a specific MT rotation, resident
experience is quite varied. Many programs do not have a toxicologist on faculty.
Future surveys will help to assess the development of MT education in EM
residency programs.
PMID- 11015280
TI - Emergency medicine resident related auto accidents-Is sleep deprivation a risk
factor?
AB - Published in: Acad Emerg Med. 2000; 7: 451.
PMID- 11015281
TI - Low-flow perfusion in the heart following global ischemia improves LV function
AB - Published in: Acad Emerg Med. 2000; 7: 508.
PMID- 11015282
TI - Preliminary experience with an emergency department observation unit protocol for
heart failure
AB - Nearly all emergency department (ED) patients with congestive heart failure (CHF)
are admitted to the hospital. Some of these patients might be best served by an
explicit protocol for observation and treatment in the ED. OBJECTIVE: To describe
the natural history of patients with CHF who are managed in an ED-based
observation unit. METHODS: Patients presenting to the ED between 7/99 and 12/99
with symptoms of CHF were screened for eligibility. Patients with hemodynamic
instability, respiratory failure, acute myocardial infarction, newonset heart
failure, or severe complicating medical disease were excluded. Patients were
managed in the observation unit for up to 12 hours before being admitted to the
hospital. Clinical parameters including heart rate (HR), respiratory rate (RR),
net diuresis, and global assessment of clinical severity (GACS) score, were
charted. Patients were followed for 30 days to determine length of hospital stay
(LOS), rates of morbidity, mortality, and readmission. RESULTS: Twenty-four
patients (15 males, 9 females; median age = 58) were enrolled in the protocol. By
4 hr a reduction in HR and RR was seen in the majority of patients (19/24 and
13/24, respectively). By 6 hr the majority (13/24) had improvement in GACS, and
by 12 hours nearly all (21/24) did. By 12 hr, most patients (13/24) had a net
diuresis of >1500 mL. Upon completion of the protocol, inpatient length of stay
was generally brief (median LOS = 1 day; range 1-8 days). At 30 days there were
no deaths or adverse events observed. Four patients were readmitted to the
hospital; 2 of these admissions were related to CHF. CONCLUSIONS: In this low
risk group of patients with CHF, most showed clinical improvement within 6 to 12
hours after ED arrival. Further study is needed to determine whether an
observation-unit protocol can safely and effectively reduce LOS for these
patients.
PMID- 11015283
TI - The penetrance of head injury management guidelines into the practice patterns of
michigan emergency physicians
AB - OBJECTIVE: The Brain Trauma Foundation published "Guidelines for the Management
of Severe Head Injury" in 1996. These evidence based clinical guidelines (CGs)
recommended against prophylactic hyperventilation and glucocorticoid use, and
advocated for blood pressure (BP) resuscitation, and the careful use of mannitol
in the event of elevated intracranial pressure (ICP). We sought to measure the
penetrance of these guidelines into the practice patterns of Michigan emergency
physicians (MEPs). METHODS: An anonymous mail survey was sent to all 566 MEPs who
are members of the American College of Emergency Physicians. Three patients with
severe head injury were presented, all with Glasgow Coma Scores (GCSs) of 8 or
less. The physicians were asked to choose from 15 diagnostic and treatment
options, which included: intubation and hyperventilation, BP resuscitation, IV
mannitol administration, and IV glucocorticoid administration. RESULTS: 319 (56%)
surveys were returned. 46% (95% CI = 40% to 51%) of MEPs elected to
inappropriately use prophylactic hyperventilation, 78% (95% CI = 75% to 81%) did
correct hypotension with systolic BP < 90 mm Hg. 83% (95% CI = 80% to 86%)
administered mannitol appropriately. Very few MEPs administered IV
glucocorticoids. CONCLUSIONS: Despite being published nearly 4 year ago, the
"Guidelines for the Management of Severe Head Injury" have not been uniformly
incorporated into the practice patterns of MEPs. Specifically, many physicians
continue to rely on prophylactic hyperventilation despite strong recommendations
against its use.
PMID- 11015284
TI - Lung inflammation and function in a model of complement-mediated acute injury
AB - Published by Acad Emerg Med. 2000; 7: 467-8.
PMID- 11015285
TI - Resident procedure and resuscitation tracking using a palm computer
AB - Resident procedure and resuscitation tracking is an onerous task required for
residency accreditation and for future hospital privilege applications by the
resident. To date, most tracking systems have been somewhat cumbersome and prone
to data loss (forms not being filled out, recorded, etc.). Our residency program
uses a palm computer database tracking system utilizing Palm III (3Com) hardware
and a custom written data collection form utilizing an inexpensive, commercially
available software package (Pendragon Forms (version 2), Pendragon Software
Corporation, Libertyville, IL). Every resident receives a Palm III on entry into
the residency. Residents enter basic demographic data and record procedures and
resuscitations into the Palm III after each encounter. Generally, each patient
logged requires approximately one minute for data entry. On a frequent basis, the
resident's Palm is 'HotSync-ed' and the recorded data transferred to the
program's central computer. Resident data are easily manipulated and reports are
generated using a common, relational database program (Access97, Microsoft
Corporation, Redmond, WA). We have found this system to be relatively
inexpensive, to improve data capture, to reduce demands on secretarial time, and
to allow improved tracking of resident procedure and resuscitation experiences.
PMID- 11015286
TI - Caspase-1-inhibitor ac-YVAD-cmk reduces LPS-lethality in rats without affecting
haematology or cytokine responses.
AB - The effect of acetyl - tyrosyl-valyl-alanyl-aspartyl - chloromethylketone (ac
YVAD-cmk), an irreversible caspase-1 (IL-1beta converting enzyme, ICE) inhibitor
on mortality, leukocyte and platelet counts and cytokine levels was investigated
in a double-blind rat model of endotoxaemia. Intravenous (i.v.) bolus
administration of lipopolysaccharide (LPS) (25-75 mg kg(-1), n=12 per group) to
anaesthetized rats induced a dose dependent increase in mortality over 8 h
(LD(50)=48 mg kg(-1)). During this period, animals became leukopenic and
thrombocytopenic. Serum levels of IL-beta, IL-6, and TNF-alpha were highly
elevated. Pretreatment of rats with ac-YVAD-cmk at a dose of 12.5 micromol kg(-1)
significantly reduced mortality from 83 to 33% using Log Rank analysis. However,
ac-YVAD-cmk did not modify blood cell counts or cytokine profiles as compared
with the LPS-drug vehicle group. These data lay credence to the potential
importance of caspase-1-inhibition in modifying the inflammatory response to
endotoxin. Further investigations are warranted in understanding the relationship
between caspase-1 inhibition, cytokine production and animal survival in
different experimental paradigms of sepsis.
PMID- 11015287
TI - On the in vitro vasoactivity of bile acids.
AB - We compared the vasorelaxant action of nine different bile acids and correlated
their vasorelaxant activity with their individual indices for hydrophobicity or
lipophilicity. Vasorelaxant activity correlated with the relative lipid
solubility of bile acids with lipophilic bile acids exhibiting the greatest
vasorelaxant activity with modest to no vasorelaxant activity exhibited by
hydrophilic bile acids. We also investigated whether bile acid-induced
vasorelaxation is mediated by antagonism of a prototypal contractile receptor,
the alpha(1)-adrenoceptor, by stimulation of a bile acid surface membrane
receptor, by the release of endothelium-derived relaxant factors, by promoting
the generation of reactive oxygen species and increasing the extent of lipid
peroxidation, or by modifying membrane fluidity. Lipophilic bile acids induce
vasorelaxation possibly by antagonizing alpha(1)-adrenoceptors, a phenomenon that
manifests itself as a lowering of the affinity of vascular alpha(1)
adrenoceptors. Bile acid-induced vasorelaxation was not dependent upon
stimulation of a bile acid surface membrane receptor or the release of
endothelium-derived relaxant factors. Lipophilic bile acids can also increase the
extent of lipid peroxidation with a subtle reduction in the fluidity of rat
vascular smooth muscle membranes not associated with loss of membrane cholesterol
or phospholipid. We have concluded that lipophilic bile acids are non-selective
vasorelaxants whose mechanism of action is a multifaceted process involving
antagonism of contractile surface membrane receptors possibly effected by an
increased extent of lipid peroxidation and/or membrane fluidity but occurs
independent of the release of endothelial-derived relaxant factors or stimulation
of a surface membrane bile acid binding site.
PMID- 11015288
TI - Cefaclor, a cephalosporin antibiotic, delays gastric emptying rate by a CCK-A
receptor-mediated mechanism in the rat.
AB - Studies in vitro suggest that cephalosporin antibiotics release the gut hormone
cholecystokinin. Cholecystokinin is known to inhibit gastric emptying. Here we
examine the effects of cefaclor on gastric emptying and intestinal motility. Male
Sprague-Dawley rats were fitted with gastric cannulas. Following a 3-week
recovery, the rate of gastric emptying of saline, peptone (4.5%) or cefaclor was
determined after instillation into the gastric cannula, while intestinal transit
was measured by using the propagation of arabic gum + charcoal mixture given
intraduodenally. Gastric emptying of saline was significantly delayed by the
addition of cefaclor (3, 10, 30 or 100 mM). The CCK-A antagonist SR-27897B (1 mg
kg(-1), i.p.) reversed the delay induced by 10 mM cefaclor, whereas the CCK-B
antagonist CI-988 (1 mg kg(-1), i.p.) had no significant effect. In capsaicin
treated rats, 10 mM cefaclor emptied more rapidly than in vehicle-treated
animals. Thirty-minute intestinal transit was increased at 30 and 100 mM of
cefaclor, while the gastric acid secretion following cefaclor instillation was no
different than the group which received saline. The cephalosporin antibiotic
cefaclor appears to be a potent stimulant of CCK release from gut endocrine
cells, resembling the effects of peptone. Cefaclor delays gastric emptying via
capsaicin-sensitive afferent pathways, which involve CCK-A receptor interaction.
PMID- 11015289
TI - RSD1019 suppresses ischaemia-induced monophasic action potential shortening and
arrhythmias in anaesthetized rabbits.
AB - The electrophysiological actions of lidocaine, tedisamil and RSD1019 were
assessed on normal and ischaemic cardiac tissue using monophasic action
potentials (MAPs) recorded from the epicardium of anaesthetized rabbits. Drug
effects on ischaemia-induced arrhythmias were assessed simultaneously in the same
rabbits. Lidocaine, infused at 2.5, 5 and 10 micromol kg(-1) min(-1) i.v.,
accelerated and worsened the electrophysiological derangement caused by
ischaemia, had profibrillatory actions and reduced the time to the occurrence of
ventricular fibrillation (VF) relative to controls. Tedisamil, infused at 0.063,
0.125 and 0.25 micromol kg(-1) min(-1) i.v., prolonged MAP duration at 90%
repolarization (MAPD(90%)) before induction of ischaemia in a dose-related
manner; however, this effect was not maintained 5 min after induction of
ischaemia. Tedisamil had no significant antiarrhythmic actions over the dose
range tested. RSD1019, infused at 2, 4 and 8 micromol kg(-1) min(-1) i.v.,
produced a small increase in MAPD(90%) before induction of ischaemia and only at
the highest dose tested. In contrast to tedisamil, RSD1019 suppressed ischaemia
induced MAP shortening assessed 5 min after induction of ischaemia. This effect
was dose-related. RSD1019 completely prevented ischaemia-induced tachyarrhythmias
at the mid and highest infusion levels tested. The results of this study
illustrate a pathologically targeted approach for preventing ischaemia-induced
arrhythmias. Suppression of ischaemia-induced MAP shortening, demonstrated herein
for RSD1019, represents a novel antifibrillatory approach.
PMID- 11015290
TI - The involvement of cytokines in the second window of ischaemic preconditioning.
AB - We utilized a rat model of myocardial infarction to investigate whether manganese
superoxide dismutase (Mn-SOD), an intrinsic radical scavenger, and tumour
necrosis factor- alpha (TNF-alpha) and/or interleukin-1beta (IL-1beta) are
involved in the late phase of ischaemic preconditioning (IP). IP was induced in
anaesthetized rats by four 3-min left coronary artery (LCA) occlusions, each
separated by 10 min of reperfusion. Twenty-four hours after the repetitive brief
ischaemia, the LCA was occluded for 20 min followed by reperfusion for 48 h. IP
reduced the infarct size by approximately 46% as determined after 48 h of
reperfusion. Antisense oligodeoxynucleotides to Mn-SOD inhibited the increases in
Mn-SOD content and activity, and abolished the expected decrease in myocardial
infarct size. Sense or scrambled oligodeoxynucleotides did not abolish either Mn
SOD induction or tolerance to ischaemia/reperfusion. The simultaneous
administration of the antibodies to TNF-alpha (0.5 ml) and IL-1beta (0.5 mg)
prior to IP abolished the cardioprotection and the increase in Mn-SOD activity
induced by IP. We conclude that the induction and activation of Mn-SOD, mediated
by TNF-alpha and IL-1beta after IP, plays an important role in the acquisition of
late-phase cardioprotection against ischaemia/reperfusion injury in rats.
PMID- 11015291
TI - Gene expression of receptors and enzymes involved in GABAergic and glutamatergic
neurotransmission in the CNS of rats behaviourally dependent on ethanol.
AB - The steady state levels of the messenger RNA (mRNA) of eight GABA(A) receptor
subunits, five glutamate receptor subunits and seven enzymes involved in the
synthesis of glutamate and GABA were measured in eight regions of rat brain in a
recently developed animal model of 'behavioural dependence' on ethanol.
'Behavioural dependence' including loss of control was induced by offering the
rats the choice between ethanol and water over a 9-month period (Group A). This
group was compared with a group given the choice between ethanol and water for
only 2 months (not yet 'behaviourally dependent', Group B), a group forced to
consume ethanol as sole fluid over a 9-month period (also not 'behaviourally
dependent', Group C) and ethanol-naive control rats (Group D). All groups were
sacrificed 1 month after the ethanol was withdrawn. The mRNA concentrations of
all eight GABA receptor subunits, four out of the five subunits of different
glutamate receptors and those of seven enzymes involved in GABA and glutamate
production were reduced almost exclusively in the parieto-occipital cortex in
Groups A and B, but not Group C. These data suggest that the synthesis of
glutamate and GABA and the activities of their respective neurons are selectively
impaired in the parieto-occipital cortex in the groups having consumed ethanol in
a free-choice design, in which its rewarding properties can better take effect
than after forced administration. As the parieto-occipital cortex is believed to
contain emotional memory structures, it may be hypothesized that the
glutamatergic and GABAergic neuronal systems in this area are involved in the
development of memory for reward from ethanol. However, they are not specifically
associated with 'behavioural dependence'.
PMID- 11015293
TI - Orphan-receptor ligand human urotensin II: receptor localization in human tissues
and comparison of vasoconstrictor responses with endothelin-1.
AB - We have determined the distribution of receptors for human urotensin-II (U-II) in
human and rat CNS and peripheral tissues. In rat, [(125)I]-U-II binding density
was highest in the abducens nucleus of brainstem (139.6+/-14 amol mm(-2)).
Moderate levels were detected in dorsal horn of spinal cord and lower levels in
aorta (22. 5+/-6 amol mm(-2)). In human tissues density was highest in skeletal
muscle and cerebral cortex ( approximately 30 amol mm(-2)), with lower levels
(<15 amol mm(-2)) in kidney cortex and left ventricle. Little binding was
identified in atria, conducting system of the heart and lung parenchyma. Receptor
density was less in human coronary artery smooth muscle (14.6+/-3 amol mm(-2),
n=10) than rat aorta with no significant difference between normal and
atherosclerotic vessels. In human skeletal muscle [(125)I]-U-II bound to a single
receptor population with K(D)=0.24+/-0.17 nM and B(max)=1.97+/-1.1 fmol mg(-1)
protein (n=4). U-II contracted human coronary, mammary and radial arteries,
saphenous and umbilical veins with sub-nanomolar EC(50) values. U-II was 50 times
more potent in arteries and <10 times more potent in veins than endothelin-1 (ET
1). The maximum response to U-II ( approximately 20% of control KCl) was
significantly less than to ET-1 ( approximately 80% KCl). In contrast, in rat
aorta, U-II and ET-1 were equipotent with similar maximum responses. This is the
first report of high affinity receptors for [(125)I]-U-II in human CNS and
peripheral tissues. This peptide produces potent, low efficacy, vasoconstriction
in human arteries and veins. These data suggest a potential role for U-II in
human physiology.
PMID- 11015292
TI - Potent stimulation and inhibition of the CFTR Cl(-) current by phloxine B.
AB - The effects of the fluoresceine derivative, phloxine B, on the Cl(-) current
through the cystic fibrosis transmembrane conductance regulator (CFTR) were
examined in Xenopus oocytes expressing human CFTR. In whole oocytes, the CFTR Cl(
) current (I(CFTR)) was activated by superfusion with isobutylmethylxanthine and
forskolin. I(CFTR) was stable during activation and deactivated rapidly upon
washout of the activation solution. Phloxine B slowed deactivation and, at high
concentrations, inhibited I(CFTR) weakly. In excised inside-out macropatches,
I(CFTR) was activated by the catalytic subunit of protein kinase A (cPKA) and
MgATP. Phloxine B (0.01 - 3 microM), applied after activation, increased I(CFTR)
within 30 s followed by a slow decrease which became dominant at high
concentrations. Slowing of deactivation of the CFTR was observed at all
concentrations. The effect of phloxine B after 30 s had a bell-shaped
concentration-dependence with midpoints at 45 and 1600 nM for the stimulatory and
the inhibitory limb, respectively; maximum stimulation was about 1.8 times. The
slow inhibitory component, measured after 6 min, occurred with an IC(50) value of
approximately 1 microM. In the absence of cPKA, phloxine B did not stimulate
I(CFTR). In the presence of cPKA and MgATP, the effects of phloxine B were more
prominent at low (0.02 mM) than at high ATP (2 mM). The data show that phloxine B
modulates I(CFTR) by increasing channel activity and slowing channel
deactivation; at high concentrations inhibition dominates. The effects may be
mediated by direct interactions with CFTR from the inside of the cell.
PMID- 11015294
TI - Inhibition of acetylcholine muscarinic M(1) receptor function by the M(1)
selective ligand muscarinic toxin 7 (MT-7).
AB - MT-7 (1 - 30 nM), a peptide toxin isolated from the venom of the green mamba
Dendroaspis angusticeps and previously found to bind selectively to the
muscarinic M(1) receptor, inhibited the acetylcholine (ACh)-stimulated [(35)S]
guanosine-5'-O-(3-thio)triphosphate ([(35)S]-GTPgammaS) binding to membranes of
Chinese hamster ovary (CHO) cells stably expressing the cloned human muscarinic
M(1) receptor subtype. MT-7 failed to affect the ACh-stimulated [(35)S]-GTPgammaS
binding in membranes of CHO cells expressing either the M(2), M(3) or M(4)
receptor subtype. In N1E-115 neuroblastoma cells endogenously expressing the M(1)
and M(4) receptor subtypes, MT-7 (0.3 - 3.0 nM) inhibited the carbachol (CCh)
stimulated inositol phosphates accumulation, but failed to affect the CCh-induced
inhibition of pituitary adenylate cyclase activating polypeptide (PACAP) 38
stimulated cyclic AMP accumulation. In both CHO/M(1) and N1E-115 cells the MT-7
inhibition consisted in a decrease of the maximal agonist effect with minimal
changes in the agonist EC(50) value. In CHO/M(1) cell membranes, MT-7 (0.05 - 25
nM) reduced the specific binding of 0.05, 1.0 and 15 nM [(3)H]-N
methylscopolamine ([(3)H]-NMS) in a concentration-dependent manner, but failed to
cause a complete displacement of the radioligand. Moreover, MT-7 (3 nM) decreased
the dissociation rate of [(3)H]-NMS by about 5 fold. CHO/M(1) cell membranes
preincubated with MT-7 (10 nM) and washed by centrifugation and resuspension did
not recover control [(3)H]-NMS binding for at least 8 h at 30 degrees C. It is
concluded that MT-7 acts as a selective noncompetitive antagonist of the
muscarinic M(1) receptors by binding stably to an allosteric site.
PMID- 11015295
TI - Developmental regulation of hippocampal excitatory synaptic transmission by
metabotropic glutamate receptors.
AB - The aims of this study were, to use agonists selective for the 3 mGlu receptor
groups to identify developmental changes in their effects, and to assess the
usefulness of proposed selective antagonists as pharmacological tools.
Hippocampal slices (400 microm) were prepared from neonate (9 - 14 days) and
young adult (5 - 7 weeks) Sprague-Dawley rats. Field excitatory postsynaptic
potentials (fEPSP) were recorded from CA1. DHPG (100 microM), a group I agonist,
produced a slowly developing enhancement of fEPSP slope in slices from adults. In
slices from neonates, DHPG (75 microM) depressed fEPSP slope. DCG-IV (500 nM), a
group II agonist, did not affect the fEPSP recorded from slices from adults
whereas perfusion in neonate slices produced a sustained depression. The group
III agonist L-AP4 (50 microM) was ineffective in adult slices but depressed fEPSP
slope in slices prepared from neonates. DHPG-induced depression of fEPSP slope
was inhibited by 4-CPG (400 microM), a group I antagonist, but was unaffected by
MCCG (500 microM) and MAP4 (500 microM), group II and III receptor antagonists
respectively. MCCG but not MAP4 antagonized the effects of DCG-IV with 4-CPG
producing variable effects. The effect of L-AP4 was unaffected by MCCG, blocked
by MAP4, and enhanced by 4-CPG. The results show that the effects of the agonists
for all groups of mGlu receptors are developmentally regulated. Furthermore, MCCG
and MAP4 behave as effective and selective antagonists for group II and group III
mGlu receptors respectively, whereas the usefulness of 4-CPG as a group I
antagonist may be limited.
PMID- 11015296
TI - Oncostatin M synergises with house dust mite proteases to induce the production
of PGE(2) from cultured lung epithelial cells.
AB - The release of PGE(2) and nitric oxide (NO) from the respiratory epithelium may
act to dampen inflammation. In other tissues, oncostatin M (OSM), a potent
inducer of epithelial antiproteases, has also been shown to interact with IL
1beta to stimulate PGE(2) release. However, whether OSM interacts with pro
inflammatory cytokines and proteases in the production of anti-inflammatory
eicosanoids and NO from airway epithelium is unknown. The effect of OSM and the
related cytokine leukaemia inhibitory factor (LIF) on PGE(2) and NO production by
the respiratory epithelial cell line, A549 in response to pro-inflammatory
cytokines as well as protease-rich house dust mite (HDM) fractions and a protease
deficient rye grass pollen extract was examined by immunohistochemistry, cell
culture, ELISA and enzyme-immunoassay. Cells treated with a mixture of IL-1beta,
IFNgamma and LPS for 48 h produced a 9 fold increase in PGE(2) and a 3 fold
increase in NO levels (both P<0.05). Both OSM and LIF were without effect.
However, OSM added together with the cytokine mixture synergistically enhanced
PGE(2) production (22 fold, P<0.05). OSM also synergistically enhanced PGE(2)
production in response to a cysteine protease-enriched, but not serine protease
enriched HDM fraction (P<0.05). Rye grass extract, neither alone nor in
combination with OSM, induced PGE(2) or NO production, although it did induce the
release of GM-CSF. These observations suggest that OSM is an important co-factor
in the release of PGE(2) and NO from respiratory epithelial cells and may play a
role in defense against exogenous proteases such as those derived from HDM.
PMID- 11015297
TI - Amphotericin B severely affects expression and activity of the endothelial
constitutive nitric oxide synthase involving altered mRNA stability.
AB - The therapeutic use of the antifungal drug amphotericin B (AmB) is limited due to
severe side effects like glomerular vasoconstriction and risk of renal failure
during AmB administration. As nitric oxide (NO) has substantial functions in
renal autoregulation, we have determined the effects of AmB on endothelial
constitutive NO synthase (ecNOS) expression and activity in human and rat
endothelial cell cultures. AmB used at concentrations of 0.6 to 1.25 microg ml(
1) led to increases in ecNOS mRNA and protein expression as well as NO
production. This was the result of an increased ecNOS mRNA half-life. In
contrast, incubation of cells with higher albeit subtoxic concentrations of AmB
(2.5 - 5.0 microg ml(-1)) resulted in a decrease or respectively in completely
abolished ecNOS mRNA and protein expression with a strongly reduced or inhibited
ecNOS activity, due to a decrease of ecNOS mRNA half-life. None of the AmB
concentrations affected promoter activity as found with a reporter gene construct
stably transfected into ECV304 cells. Thus, our experiments show a concentration
dependent biphasic effect of AmB on expression and activity of ecNOS, an effect
best explained by AmB influencing ecNOS mRNA stability. In view of the known
renal accumulation of this drug the results reported here could help to elucidate
its renal toxicity.
PMID- 11015298
TI - Histamine H(2) receptors mediate the inhibitory effect of histamine on human
eosinophil degranulation.
AB - The effect of histamine on human eosinophil degranulation and the receptor
mediating such effect were studied in vitro using the complement C5a-mediated
eosinophil peroxidase (EPO) release model. Following pre-treatment with 5 microg
ml(-1) cytochalasin B(CB), C5a induced a concentration-dependent release of EPO
from eosinophils isolated from healthy donors. Histamine (0.1-50 microM), but not
L-histidine, inhibited concentration-dependently C5a-induced EPO release with
IC(50) (95% CI) of 0.6 microM (0.3-1.2 microM) and maximal inhibition of
approximately 60%. A similar effect was seen with the selective H(2) agonists
dimaprit (IC(50) (95% CI)=6.9 microM (3.2-10.6 microM)) and amthamine (IC(50)
(95% CI)=0.4 microM (0.2-0.7 microM)). Neither the selective H(1) agonist 6-(2-(4
imidazolyl)ethylamino)-N-(4-trifluoromethylphenyl) heptanecarboxamide(HTMT), nor
the selective H(3) agonists imetit (up to 100 microM) had any significant effect.
The inhibition by histamine was reversed by cimetidine (0.1-30 microM) and other
H(2) antagonists, but not the H(1) antagonist mepyramine (1.0- 100 microM), nor
the H(3) antagonist thioperamide (1.0-100 microM). Cimetidine (1-30 microM)
shifted to the right the dimaprit log dose-response curve, producing a pA(2)
value of 5.9 and Schild's plot slope of 0.98, thus confirming simple competitive
antagonism. Histamine (10-100 microM) increased intracellular level of adenosine
3',5'-cyclic monophosphate, which was completely abolished by cimetidine (30
microM), but not mepyramine or thioperamide. The cyclic AMP analogue - dibutyryl
cyclic AMP - also inhibited degranulation (IC(50) approximately 300 microM). The
cyclic AMP phosphodiesterase(PDE) IV inhibitor rolipram (10 microM)
synergistically enhanced the inhibition of EPO release by histamine. These
results suggest that histamine, via stimulation of H(2) receptors and a
consequent elevation of intracellular levels of cyclic AMP, inhibits human
eosinophil degranulation.
PMID- 11015299
TI - Differential regulation of P2Y(11) receptor-mediated signalling to phospholipase
C and adenylyl cyclase by protein kinase C in HL-60 promyelocytes.
AB - The regulatory mode of the P2Y(11) purinoceptor-mediated signalling cascades
towards phospholipase C and adenylyl cyclase was studied in HL-60 promyelocytes.
Treatment with the potent P2Y(11) receptor activator dATP evoked an elevated
intracellular Ca(2+) concentration ([Ca(2+)](i)) and inositol 1,4,5-trisphosphate
(IP(3)) production that was sustained for longer than 30 min. However, the dATP
induced responses were significantly inhibited by the activation of protein
kinase C after a short exposure to phorbol 12-myristate 13-acetate (PMA). dATP
also potently stimulated cyclic AMP production with half maximum effect seen at
23+/-7 microM dATP. In addition, a 5-min pretreatment with PMA enhanced the dATP
stimulated cyclic AMP accumulation. PMA potentiated the cyclic AMP production
when adenylyl cyclase was activated directly by forskolin or indirectly by G
protein activation after cholera toxin treatment. dATP also enhanced the
forskolin-mediated cyclic AMP generation. Treatment of the cells with 10 microM U
73122, which almost completely blocked the dATP-stimulated IP(3) production and
[Ca(2+)](i) rise, had no effect on cyclic AMP accumulation, while 10 microM 9
(tetrahydro-2-furyl)adenine (SQ 22536), which inhibited the adenylyl cyclase
activation, did not effect the dATP-stimulated phosphoinositide turnover. Taken
together, the results indicate that P2Y(11) receptor-mediated activation of
phospholipase C and adenylyl cyclase occurs through independent pathways and is
differentially regulated by protein kinase C in HL-60 cells.
PMID- 11015300
TI - Differences in the pharmacological properties of rat and chicken brain fatty acid
amidohydrolase.
AB - The pharmacological properties of fatty acid amidohydrolase (FAAH) were
investigated in brains of 35-day-old chickens, since nothing is known about the
enzyme in avian species. FAAH activity towards both [(3)H]-palmitoylethanolamide
(PEA) [K(M)=1.5 microM] and [(3)H]-anandamide (AEA) [K(M)=5.4 microM] was
demonstrated in the chicken brains. The chicken FAAH was inhibited by the
substrate analogues oleyl trifluoromethylketone (OTMK) and diazomethylarachidonyl
ketone (DAK) with similar potencies to the rat FAAH. However, in contrast to the
rat brain, phenylmethylsulphonyl fluoride (PMSF) and the enantiomers of ibuprofen
had very weak effects on chicken brain FAAH. Indomethacin and niflumic acid were
found to inhibit rat brain AEA hydrolysis. The inhibition by indomethacin was
reversible and competitive, with a K(i) value of 120 microM. Chicken FAAH was
less sensitive to indomethacin than its rodent counterpart, but the inhibition
was also competitive (K(i)). It is concluded that chicken FAAH activity has
different pharmacological properties to its rodent counterpart.
PMID- 11015301
TI - The effects of caffeine on ATP-sensitive K(+) channels in smooth muscle cells
from pig urethra.
AB - The effects of caffeine on both levcromakalim-induced macroscopic and unitary
currents in pig proximal urethra were investigated by the use of patch-clamp
techniques (conventional whole-cell configuration and cell-attached
configuration). The effects of caffeine were also examined on currents in inside
out patches of COS7 cells expressing carboxy terminus truncated inwardly
rectifying K(+) channel (Kir6.2) subunits (i.e. Kir6.2DeltaC36) which form ATP
sensitive K(+) channels (K(ATP) channels). In conventional whole-cell
configuration, the levcromakalim (100 microM)-induced inward current (symmetrical
140 mM K(+) conditions) was inhibited by caffeine (> or =1 mM) at a holding
potential of -50 mV. In contrast, ryanodine (10 microM) caused no significant
inhibitory effect on the gradual decay of the levcromakalim-induced current at
50 mV. The amplitude of the 30 microM levcromakalim-induced current was enhanced
by 3-isobutyl-1-methylxanthine (IBMX, 100 microM). In cell-attached
configuration, the levcromakalim-induced K(+) channel openings were inhibited by
subsequent application of 10 mM caffeine, decreasing the channel open probability
at -50 mV. Reverse transcriptase-polymerase chain reaction (RT - PCR) analysis
revealed the presence of Kir6.2 transcript in pig urethra. Caffeine (> or =3 mM)
inhibited the channel activity of Kir6.2DeltaC36 expressed in COS7 cells (3 mM
caffeine, 65+/-6%, n=4; 10 mM caffeine, 29+/-2%, n=4). These results suggest that
caffeine can inhibit the activity of K(ATP) channels through a direct blocking
effect on the pore-forming Kir subunit.
PMID- 11015302
TI - Advantages of heterologous expression of human D2long dopamine receptors in human
neuroblastoma SH-SY5Y over human embryonic kidney 293 cells.
AB - The human D2long dopamine receptor when expressed heterologously in a human
neuronal cell line, SH-SY5Y, produced more robust functional signals than when
expressed in a human embryonic kidney cell line, HEK293. Quinpirole (agonist)
induced GTPgamma(35)S binding and high affinity sites were 3 - 4 fold greater in
SH-SY5Y than in HEK293 cells. N-type Ca(2+) channel currents present in SH-SY5Y
cells, but not HEK293 cells, were inhibited potently by quinpirole with a half
maximal inhibitory concentration of 0.15+/-0.03 nM. Inhibition of adenylyl
cyclases by agonists, on the other hand, was of similar potency and efficacy in
the two cell lines. GTPgamma(35)S-Bound Galpha subunits from quinpirole-activated
and solubilized membranes were monitored upon immobilization with various Galpha
specific antibodies. Galpha(i) and Galpha(o) subunits were highly labelled with
GTPgamma(35)S in SH-SY5Y cells, but only Galpha(i) subunits were labelled in
HEK293 cells. The additional G(o) coupling in SH-SY5Y cells could arise, at least
in part, from the presence of G(o) coupled-effectors, such as the N-type Ca(2+)
channel, and may contribute to robust agonist-induced GTPgamma(35)S binding,
which is a reliable means for measuring ligand intrinsic efficacy. It appears
that expression of neuronal G protein-coupled receptors in neuronal environments
could reveal additional functional characteristics that are absent in non
neuronal cell lines. This appears to be due to, at least in part, to the presence
of neuron-specific effectors. These findings underscore the importance of the
cellular environment in which drug actions are examined, particularly in the face
of intensive efforts to develop drugs for G protein-coupled receptors of various
origins.
PMID- 11015303
TI - Nitric oxide and sodium nitroprusside-induced relaxation of the human umbilical
artery.
AB - In the human umbilical artery (HUA) pre-contracted with the thromboxane mimetic
U46619 or with 5-hydroxytryptamine (5-HT), (and pretreated with indomethacin (3
microM) to suppress the synthesis of prostanoids), authentic nitric oxide (NO)
evoked concentration-dependent relaxation (pEC(50) 7.05 and 5.99, respectively).
In contrast, sodium nitroprusside (SNP) induced relaxation only in U46619 pre
contracted HUA (pEC(50) 6.52). At high (>300 mmHg) vs low (<55 mmHg) oxygen
tension the dose-response curves to NO- and SNP-induced relaxations were biphasic
and shifted leftward. Preincubation of the arterial rings with the soluble
guanylyl cyclase (sGC) inhibitor 1H[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one
(ODQ; 10 microM) shifted the concentration-response curve to NO, reduced the
maximal relaxation response to NO (E(max) 71%) and to SNP (E(max) 10%). Pre
exposure of HUA rings to high extracellular K(+) (50 mM) reduced E(max)
relaxation responses to NO (36%) and SNP (1%). Pretreatment of the HUA with the
K(+) channel inhibitors, tetraethylammonium (TEA, 1 mM), 4-aminopyridine (4-AP,
0.5 mM), charybdotoxin (0.1 microM) or iberiotoxin (0.1 microM) increased the
pEC(30) for NO and SNP and changed the shape of the dose-response curves from
biphasic to monophasic. Pre-incubation of HUA rings with TEA (1 mM), 4-AP (0.5
mM) and ODQ (10 microM) significantly reduced the NO-induced maximal relaxation
(E(max) 26%) but not the pEC(50) (5.60). These data indicate that SNP-induced
relaxation in the HUA is primarily mediated via sGC-cyclic GMP whereas NO-induced
relaxation also involves the activation of K(V) and K(Ca) channels and a cyclic
GMP/K(+) channel-independent mechanism(s).
PMID- 11015304
TI - Effects of tetrandrine on calcium transport, protein fluorescences and membrane
fluidity of sarcoplasmic reticulum.
AB - To understand whether the molecular mechanism of Tetrandrine (Tet)'s
pharmacological effects is concerned with sarcoplasmic reticulum calcium
transport so as to be involved in myocardial contractility, we observed the
effects of Tet on calcium transport and membrane structure of rabbit skeletal
muscle sarcoplasmic reticulum vesicles (SR) and rat cardiac sarcoplasmic
reticulum vesicles (CSR). Calcium uptake was monitored with a dual-wavelength
spectrophotometer. Protein conformation and fluorescence polarization were
measured by fluospectrophotometric method and membrane lipids labelled with
fluorescence probes for SR, respectively. 128 micromol l(-1) Tet reduced the
initial rate of calcium uptake to 59% of control 6 min after reaction. Tet un
competitively inhibited SR Ca(2+), Mg(2+)-ATPase activity, causing the
stoichiometric ratio of SR Ca(2+)/ATP to decrease to 1.43 from 2.0 of control.
Inhibitory rates on SR Ca(2+),Mg(2+)-ATPase by Tet were reduced from 60% in the
absence of phosphate to 50% in the presence of phosphate and reduced from 92% in
1 mmol l(-1) ATP to 60% in 5 mmol l(-1) ATP. Tet markedly reduced SR intrinsic
protein fluorescence, while it slightly decreased the thiol(SH)-modified protein
fluorescence of SR labelled with N-(3-pyrene)-maleimide. Tet slightly increased
fluorescence polarization in the middle and deep layers of SR membrane lipids
labelled with 7- or 12-(9-anthroyloxy) stearic acid (AS) probes, whereas it did
not change that of SR labelled with 1, 6-diphenyl-1,3,5-hexatrine (DPH). These
results revealed that prevention of SR calcium uptake by Tet was due to
inhibition of the SR calcium pump Ca(2+),Mg(2+)-ATPase, changes in spatial
conformation of the pumps protein molecules and a decrease in the extent of
motion of membrane lipid molecules, thus altering the regulation of [Ca(2+)](i)
and myocardial contractility.
PMID- 11015305
TI - Influence of beta-adrenoceptor tone on the cardioprotective efficacy of adenosine
A(1) receptor activation in isolated working rat hearts.
AB - This study investigated the role of beta-adrenoceptors in the cardioprotective
and metabolic actions of adenosine A(1) receptor stimulation. Isolated paced (300
beats min(-1)) working rat hearts were perfused with Krebs-Henseleit solution
containing 1.2 mM palmitate. Left ventricular minute work (LV work), O(2)
consumption and rates of glycolysis and glucose oxidation were measured during
reperfusion (30 min) following global ischaemia (30 min) as well as during
aerobic conditions. Relative to untreated hearts, N(6)-cyclohexyladenosine (CHA,
0.5 microM) improved post-ischaemic LV work (158%) and reduced glycolysis and
proton production (53 and 42%, respectively). CHA+propranolol (1 microM) had
similar beneficial effects, while propranolol alone did not affect post-ischaemic
LV work or glucose metabolism. Isoprenaline (10 nM) impaired post-ischaemic
function and after 25 min ischaemia recovery was comparable with 30 min ischaemia
in untreated hearts (41 and 53%, respectively). Relative to isoprenaline alone,
CHA+isoprenaline improved recovery of LV work (181%) and reduced glycolysis and
proton production (64 and 60%, respectively). In aerobic hearts, CHA, propranolol
or CHA+propranolol had no effect on LV work or glucose oxidation. Glycolysis was
inhibited by CHA, propranolol and CHA+propranolol (50, 53 and 52%, respectively).
Isoprenaline-induced increases in heart rate, glycolysis and proton production
were attenuated by CHA (85, 57 and 53%, respectively). The cardioprotective
efficacy of CHA was unaffected by antagonism or activation of beta-adrenoceptors.
Thus, the mechanism of protection by adenosine A(1) receptor activation does not
involve functional antagonism of beta-adrenoceptors.
PMID- 11015306
TI - Inverse agonism and neutral antagonism at a constitutively active alpha-1a
adrenoceptor.
AB - We have studied the antagonist action of prazosin and KMD-3213 in a
constitutively active mutant of the human alpha-1a adrenoceptor in which Ala(271)
was substituted to Thr and was expressed in CHO cells. Inverse agonism was
characterized by up-regulation of receptor density, a decrease in basal GTPgammaS
binding, and a reduction in basal inositol-1,4,5-trisphosphate (IP(3)) level.
According to the above criteria, prazosin acted as an inverse agonist, whilst KMD
3213 behaved as a neutral antagonist. Compared with the wild-type receptor,
mutant receptor exhibited single affinity sites for [(3)H]-prazosin, [(3)H]-KMD
and the non-radioactive ligands tested, and displayed significantly higher
affinities for several agonists but not for the two antagonists. Administration
of KMD-3213 to prazosin-treated CHO cells expressing the mutant receptor reversed
the inverse agonism of prazosin resulting in rapid increases in cellular IP(3),
in intracellular [Ca(2+)] and in the rate of extracellular acidification. These
results indicated that a neutral antagonist can reverse the action of an inverse
agonist at the receptor site. The distinct properties of inverse agonist and
neutral antagonist in affecting receptor function may be important for the
clinical use of such antagonists.
PMID- 11015307
TI - Inhibition of small G proteins of the rho family by statins or clostridium
difficile toxin B enhances cytokine-mediated induction of NO synthase II.
AB - In order to investigate the involvement of Ras and/or Rho proteins in the
induction of the inducible isoform of nitric oxide synthase (NOS II) we used HMG
CoA reductase inhibitors (statins) and Clostridium difficile toxin B (TcdB) as
pharmacological tools. Statins indirectly inhibit small G proteins by preventing
their essential farnesylation (Ras) and/or geranylgeranylation (Rho). In
contrast, TcdB is a glucosyltransferase and inactivates Rho-proteins directly.
Human A549/8- and DLD-1 cells as well as murine 3T3 fibroblasts were preincubated
for 18 h with statins (1 - 100 microM) or TcdB (0.01-10 ng ml(-1)). Then NOS II
expression was induced by cytokines. NOS II mRNA was measured after 4 - 8 h by
RNase protection assay, and NO production were measured by the Griess assay after
24 h. Statins and TcdB markedly increased cytokine-induced NOS II mRNA expression
and NO production. Statin-mediated enhancement of NOS II mRNA expression was
reversed almost completely by cotreatment with mevalonate or
geranylgeranylpyrophosphate. It was only slightly reduced by
farnesylpyrophosphate. Therefore, small G proteins of the Rho family are likely
to be involved in NOS II induction. In A549/8 cells stably transfected with a
luciferase reporter gene under the control of a 16 kb fragment of the human NOS
II promoter (pNOS2(16)Luc), statins produced only a small increase in cytokine
induced NOS II promoter activity. In contrast, statins had a considerable
superinducing effect in DLD-1 cells stably transfected with pNOS2(16)Luc. In
conclusion, our studies provide evidence that statins and TcdB potentiate
cytokine-induced NOS II expression via inhibition of small G proteins of the Rho
family. This in turn results in an enhanced NOS II promoter activity and/or a
prolonged NOS II mRNA stability.
PMID- 11015308
TI - Contractile responses to sumatriptan and ergotamine in the rabbit saphenous vein:
effect of selective 5-HT(1F) receptor agonists and PGF(2alpha).
AB - Contractile responses to ergotamine, sumatriptan and the novel 5-HT(1F) receptor
agonists, LY334370 and LY344864 were examined using the rabbit saphenous vein.
Ergotamine (pEC(50)=8.7+/-0.06) was 30 fold more potent than 5-hydroxytryptamine
(5-HT) (pEC(50)=7.2+/-0.13) and 300 fold more potent than sumatriptan
(pEC(50)=6.0+/-0.08) in contracting the rabbit saphenous vein in vitro. The
selective 5-HT(1F) receptor agonists, LY334370 or LY344864 (up to 10(-4) M), did
not contract the rabbit saphenous vein. The contractile response to ergotamine in
this tissue resulted from activation of both alpha(1) and 5-HT(1B/1D) receptors
based on the observation that prazosin (10(-6) M), an alpha-adrenoceptor
antagonist, and GR127935 (10(-8) M) a 5-HT(1B/1D) receptor antagonist, dextrally
shifted the contractile response to ergotamine. In contrast, prazosin (10(-6) M)
did not alter contraction to sumatriptan whereas GR127935 (10(-8) M) was a potent
antagonist (-log K(B)=10.0) suggesting that sumatriptan-induced contraction of
the rabbit saphenous vein was mediated only by activation of receptors similar or
identical to 5-HT(1B/1D) receptors. PGF(2alpha) (3x10(-7) M) produced a modest
increase (approximately 5.0 - 10.0% maximum PGF(2alpha) contraction) in saphenous
vein force. Precontraction with PGF(2alpha) (3x10(-7) M) dramatically augmented
the potency and maximal contractile response to sumatriptan (pEC(50)=7.1) and
modestly enhanced the contractile potency of ergotamine (pEC(50)=9.0) in the
rabbit saphenous vein. However, PGF(2alpha) (3x10(-7) M) only unmasked a
contraction to the 5-HT(1F) receptor agonists when concentrations exceeded 10(-5)
M, concentrations considerably higher than their 5-HT(1F) receptor affinities.
LY334370 (10(-6) M) pretreatment did not alter contraction to either sumatriptan
or ergotamine and a higher concentration (10(-5) M) of LY334370 or LY344864
inhibited contraction to sumatriptan. Thus, activation of 5-HT(1F) receptors will
not induce vascular contraction (either alone or following modest tone with
PGF(2alpha)) or augment contraction to other contractile agonists in the rabbit
saphenous vein.
PMID- 11015309
TI - The bee venom peptide tertiapin underlines the role of I(KACh) in acetylcholine
induced atrioventricular blocks.
AB - Acetylcholine (ACh) is an important neuromodulator of cardiac function that is
released upon stimulation of the vagus nerve. Despite numerous reports on
activation of I(KACh) by acetylcholine in cardiomyocytes, it has yet to be
demonstrated what role this channel plays in cardiac conduction. We studied the
effect of tertiapin, a bee venom peptide blocking I(KACh), to evaluate the role
of I(KACh) in Langendorff preparations challenged with ACh. ACh (0.5 microM)
reproducibly and reversibly induced complete atrioventricular (AV) blocks in
retroperfused guinea-pig isolated hearts (n=12). Tertiapin (10 to 300 nM) dose
dependently and reversibly prevented the AV conduction decrements and the
complete blocks in unpaced hearts (n=8, P<0.01). Tertiapin dose-dependently
blunted the ACh-induced negative chronotropic response from an ACh-induced
decrease in heart rate of 39+/-16% in control conditions to 3+/-3% after 300 nM
tertiapin (P=0.01). These effects were not accompanied by any significant change
in QT intervals. Tertiapin blocked I(KACh) with an IC(50) of 30+/-4 nM with no
significant effect on the major currents classically associated with cardiac
repolarisation process (I(Kr), I(Ks), I(to1), I:(sus), I(K1) or I(KATP)) or AV
conduction (I(Na) and I(Ca(L))). In summary, tertiapin prevents dose-dependently
ACh-induced AV blocks in mammalian hearts by inhibiting I(KACh).
PMID- 11015310
TI - Dual modulation by thrombin of the motility of rat oesophageal muscularis mucosae
via two distinct protease-activated receptors (PARs): a novel role for PAR-4 as
opposed to PAR-1.
AB - Since protease-activated receptors (PARs) are distributed throughout the
gastrointestinal tract, we investigated the role of PARs in modulation of the
motility of the rat oesophageal muscularis mucosae. Thrombin produced contraction
of segments of the upper and lower part of the smooth muscle. Trypsin contracted
both the muscle preparations only at high concentrations. SFLLR-NH(2) and TFLLR
NH(2) (PAR-1-activating peptides), but not the PAR-1-inactive peptide FSLLR
NH(2), evoked a marked contraction. In contrast, the PAR-2 agonist SLIGRL-NH(2)
and the PAR-4 agonist GYPGKF-NH(2) caused no or only a negligible contraction. In
oesophageal preparations precontracted with carbachol, thrombin produced a dual
action i.e. relaxation followed by contraction. TFLLR-NH(2) further contracted
the precontracted preparations with no preceding relaxation. GYPGKF-NH(2), but
not the inactive peptide GAPGKF-NH(2), produced marked relaxation. Trypsin or
SLIGRL-NH(2) caused no relaxation. The PAR-1-mediated contraction was completely
abolished in Ca(2+)-free medium and considerably attenuated by nifedipine (1
microM) and in a low Na(+) medium. The PAR-4-mediated relaxation was resistant to
tetrodotoxin (10 microM), apamin (0.1 microM), charybdotoxin (0.1 microM), L-N(G)
nitroarginine methyl ester (100 microM), indomethacin (3 microM), propranolol (5
microM) or adenosine 3', 5'-cyclic monophosphorothioate, 8-bromo, Rp-isomer (30
microM). Thus, thrombin plays a dual role in modulating the motility of the
oesophageal muscularis mucosae, producing contraction via PAR-1 and relaxation
via PAR-4. The PAR-1-mediated effect appears to occur largely through increased
Na(+) permeability followed by activation of L-type Ca(2+) channels and
subsequent influx of extracellular Ca(2+). Our data could provide evidence for a
novel role of PAR-4 as opposed to PAR-1, although the underlying mechanisms are
still open to question.
PMID- 11015311
TI - Prodigiosin from the supernatant of Serratia marcescens induces apoptosis in
haematopoietic cancer cell lines.
AB - The effects of supernatant from the bacterial strain Serratia marcescens 2170 (CS
2170) on the viability of different haematopoietic cancer cell lines (Jurkat,
NSO, HL-60 and Ramos) and nonmalignant cells (NIH-3T3 and MDCK) was studied. We
examined whether this cytotoxic effect was due to apoptosis, and we purified the
molecule responsible for this effect and determined its chemical structure. Using
an MTT assay we showed a rapid (4 h) decrease in the number of viable cells. This
cytotoxic effect was due to apoptosis, according to the fragmentation pattern of
DNA, Hoechst 33342 staining and FACS analysis of the phosphatidylserine
externalization. This apoptosis was blocked by using the caspase inhibitor Z
VAD.fmk, indicating the involvement of caspases. Prodigiosin is a red pigment
produced by various bacteria including S. marcescens. Using mutants of S.
marcescens (OF, WF and 933) that do not synthesize prodigiosin, we further showed
that prodigiosin is involved in this apoptosis. This evidence was corroborated by
spectroscopic analysis of prodigiosin isolated from S. marcescens. These results
indicate that prodigiosin, an immunosuppressor, induces apoptosis in
haematopoietic cancer cells with no marked toxicity in nonmalignant cells,
raising the possibility of its therapeutic use as an antineoplastic drug.
PMID- 11015312
TI - The effect of Gi-protein inactivation on basal, and beta(1)- and beta(2)AR
stimulated contraction of myocytes from transgenic mice overexpressing the
beta(2)-adrenoceptor.
AB - The atria and ventricles of transgenic mice (TGbeta(2)) with cardiac
overexpression of the human beta(2)-adrenoceptor (beta(2)AR) were initially
reported to show maximum contractility in the absence of beta-AR stimulation.
However, we have previously observed a different phenotype in these mice, with
myocytes showing normal contractility but reduced betaAR responses. We have
investigated the roles of cyclic AMP and Gi in basal and betaAR function in these
myocytes. ICI 118,551 at inverse agonist concentrations decreased contraction by
32%. However, the cyclic AMP antagonist Rp-cAMPS had no effect on contraction in
TGbeta(2) myocytes, indicating that there was no tonic influence of raised cyclic
AMP. These findings cannot be explained by the proposed model for inverse
agonism, where the activated receptor (R*) raises cyclic AMP levels and so
increases contraction in the absence of agonist. After pertussis toxin (PTX)
pretreatment to produce inactivation of Gi, the basal contraction in 1 mM Ca(2+)
was increased in TGbeta(2) mice (7.82+/-0.47%, n=23) compared to LM mice (3.60+/
0.59%, n=11) (P<0.001). The contraction amplitude of myocytes to the maximal
concentration of isoprenaline was also increased significantly by PTX in
TGbeta(2) mice (9.40+/-1.22%, n=8) and was no longer reduced compared to LM mice
(8.93+/-1.50%, n=11). Both beta(1)- and beta(2)AR subtypes were affected both by
the original desensitization and by the resensitization with PTX. PTX treatment
has therefore restored the original phenotype, with high basal contractility and
little further effect of isoprenaline. We suggest that both beta-AR
desensitization and lack of increased basal contraction in ventricular myocytes
from our colony of TGbeta(2) mice were due to increased activity of PTX-sensitive
G-proteins.
PMID- 11015313
TI - Regulation of the human prostanoid TPalpha and TPbeta receptor isoforms mediated
through activation of the EP(1) and IP receptors.
AB - The intermolecular cross-regulation mediated by the prostanoid IP-receptor
(IP)/EP(1) receptor (EP(1)) agonists PGI(2) and 17 phenyl trinor PGE(2) on TP
receptor (TP) signalling within platelets was compared to that which occurs to
the individual TPalpha and TPbeta receptors over-expressed in human embryonic
kidney (HEK) 293 cells. Ligand mediated TP receptor activation was monitored by
analysing mobilization of intracellular calcium ([Ca(2+)](i)) following
stimulation with the selective thromboxane (TX) A(2) mimetic U46619. Consistent
with previous studies, in platelets, PGI(2) acting through endogenous IP
receptors completely inhibited U46619-mediated TP receptor signalling in a
protein kinase (PK) A-dependent, PKC-independent manner. In HEK 293 cells,
PGI(2), acting through endogenous AH6809 sensitive EP(1) rather than IP
receptors, and the selective EP(1) receptor agonist 17 phenyl trinor PGE(2)
antagonized U46619-mediated signalling by both TPalpha and TPbeta receptors in a
PKC-dependent, PKA-independent manner. The maximum response induced by either
ligand was significantly (P<0.005) greater for the TPalpha receptor than the
TPbeta receptor, pointing to possible physiologic differences between the TP
isoforms, although the potency of each ligand was similar for both TP receptors.
TP(Delta328), a truncated variant of TP receptor lacking the C-tail sequences
unique to TPalpha or TPbeta receptors, was not sensitive to EP(1) receptor
mediated regulation by PGI(2) or 17 phenyl trinor PGE(2) In conclusion, these
data confirm that TPalpha and TPbeta receptors are subject to cross regulation by
EP(1) receptor signalling in HEK 293 cells mediated by PKC at sites unique to the
individual TP receptors and that TPalpha receptor responses are significantly
more reduced by EP(1) receptor regulation than those of the TPbeta receptor.
PMID- 11015314
TI - Effects of (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), sigma (sigma)
ligands, on micturition in anaesthetized rats.
AB - The effects of two sigma (sigma) binding site ligands, (+)-pentazocine and 1,3-di
o-tolylguanidine (DTG), on bladder functions were examined in rats. Cystometry
using urethane-anaesthetized rats showed that (+)-pentazocine (1 - 5 mg kg(-1),
i.v.) and DTG (1 - 5 mg kg(-1), i.v.) prolonged micturition intervals, indicating
increased bladder capacity and raised the threshold pressure. The effects of (+)
pentazocine (2 mg kg(-1), i.v. ) on micturition were not influenced by naloxone
(0.5 mg kg(-1), i.v. ), which antagonized similar effects of morphine (2 mg kg(
1), i.v.). When administered intracerebroventricularly (i.c.v.), DTG (1 microg)
and (+)-pentazocine (30 microg) prolonged micturition intervals with increased
threshold pressure on the cystometrogram. In isolated bladder detrusor strips of
rats, (+)-pentazocine (3 microM) and DTG (1 microM) did not affect contractile
responses to electrical field stimulation. A higher concentration of DTG (3
microM) slightly suppressed the response induced by 30 Hz stimulation. The
effects of (+)-pentazocine and DTG on micturition were abolished by pre-treatment
with pertussis toxin (PTX, 1 microg, i.c.v.). These results indicate that typical
sigma ligands, such as (+)-pentazocine and DTG, increase bladder capacity in
anaesthetized rats. Moreover, the mechanism by which sigma ligands change the
urinary storage properties in rats may involve pathways in which the function of
Gi/o proteins is necessary.
PMID- 11015315
TI - The effect of nucleotides and adenosine on stimulus-evoked glutamate release from
rat brain cortical slices.
AB - Evidence has previously been presented that P1 receptors for adenosine, and P2
receptors for nucleotides such as ATP, regulate stimulus-evoked release of
biogenic amines from nerve terminals in the brain. Here we investigated whether
adenosine and nucleotides exert presynaptic control over depolarisation-elicited
glutamate release. Slices of rat brain cortex were perfused and stimulated with
pulses of 46 mM K(+) in the presence of the glutamate uptake inhibitor L-trans
pyrrolidine-2,4-dicarboxylic acid (0.2 mM). High K(+) substantially increased
efflux of glutamate from the slices. Basal glutamate release was unchanged by the
presence of nucleotides or adenosine at concentrations of 300 microM. Adenosine,
ATP, ADP and adenosine 5'-O-(3-thiotriphoshate) at 300 microM attenuated
depolarisation-evoked release of glutamate. However UTP, 2-methylthio ATP, 2
methylthio ADP, and alpha,beta-methylene ATP at 300 microM had no effect on
stimulated glutamate efflux. Adenosine deaminase blocked the effect of adenosine,
but left the response to ATP unchanged. The A(1) antagonist 8-cyclopentyl-1, 3
dipropylxanthine antagonised the inhibitory effect of both adenosine and ATP.
Cibacron blue 3GA inhibited stimulus-evoked glutamate release when applied alone.
When cibacron blue 3GA was present with ATP, stimulus-evoked glutamate release
was almost eliminated. However, this P2 antagonist had no effect on the
inhibition by adenosine. These results show that the release of glutamate from
depolarised nerve terminals of the rat cerebral cortex is inhibited by adenosine
and ATP. ATP appears to act directly and not through conversion to adenosine.
PMID- 11015316
TI - Vagal neurotransmission to the ferret lower oesophageal sphincter: inhibition via
GABA(B) receptors.
AB - GABA(B) receptors modulate the function of the lower oesophageal sphincter (LOS)
in vivo by inhibiting neurotransmitter release in the vagal pathway controlling
LOS relaxation. We aimed to determine whether this effect was mediated
peripherally on vagal motor outflow to the ferret LOS in vitro. The LOS, with
intact vagal innervation, was prepared from adult ferrets and LOS tension
measured. Vagal stimulation (0.5 - 10 Hz, 30 V) evoked a tetrodotoxin-sensitive,
frequency-dependent relaxation. Both GABA (3x10(-4) M) and (+/-)baclofen (2x10(
4) M) inhibited vagally-stimulated LOS relaxation. The potent GABA(B) receptor
selective agonist 3-APPA dose-dependently inhibited vagally-stimulated LOS
relaxation, with an EC(50) value of 0.7 microM Decreased responses following
vagal stimulation in the presence of (+/-)baclofen or 3-APPA were reversed with
the potent GABA(B) receptor antagonist CGP 62349. Neither CGP 62349 nor muscimol
(GABA(A) receptor agonist) alone affected LOS responses following vagal
stimulation. Agonists of other G protein-coupled receptors (clonidine (alpha(2)
adrenoceptor) (5x10(-6) M), U50488 (kappa opioid) (10(-5) M), neuropeptide Y (10(
6) M)) did not affect vagally-mediated LOS relaxation. The present study supports
a discrete presynaptic inhibitory role for GABA(B) receptors on vagal
preganglionic fibres serving inhibitory motorneurones in the ferret LOS.
PMID- 11015317
TI - Suppression of the development of hypertension by the inhibitor of inducible
nitric oxide synthase.
AB - Our previous study demonstrated that the aortic inducible nitric oxide synthase
(iNOS) expression and the plasma nitrite level in spontaneously hypertensive rats
(SHR) were greater than that in age-matched Wistar-Kyoto rats (WKY). We
subsequently hypothesized that the over-expression of iNOS might play an
important role in the pathogenesis of hypertension in SHR. In the present study,
pyrrolidinedithiocarbamate (PDTC, 10 mg kg(-1) day(-1), p.o., antioxidant and
nuclear factor-kappa B inhibitor) and aminoguanidine (15 mg kg(-1) day(-1), p.o.,
selective inhibitor of iNOS) was used to treat SHR and WKY from age of 5 weeks
through 16 weeks. We found that PDTC and aminoguanidine significantly suppressed
the development of hypertension and improved the diminished vascular responses to
acetylcholine in SHR but not in WKY. Likewise, the increase of iNOS expression,
nitrotyrosine immunostaining, nitric oxide production and superoxide anion
formation in adult SHR were also significantly suppressed by chronic treatment
with PDTC and aminoguanidine. In conclusion, this study demonstrated that both
PDTC and aminoguanidine significantly attenuated the development of hypertension
in SHR. The results suggest that PDTC suppresses iNOS expression due to its anti
oxidant and/or nuclear factor-kappa B inhibitory properties. However, the effect
of aminoguanidine was predominantly mediated by inhibition of iNOS activity,
thereby reducing peroxynitrite formation. We propose that the development of a
more specific and potent inhibitor of iNOS might be beneficial in preventing
pathological conditions such as the essential hypertension.
PMID- 11015318
TI - Pharmacological analysis by HOE642 and KB-R9032 of the role of Na(+)/H(+)
exchange in the endothelin-1-induced Ca(2+) signalling in rabbit ventricular
myocytes.
AB - The role of Na(+)/H(+) exchange in endothelin-1 (ET-1)-induced increases in
Ca(2+) transients and cell shortening was studied in rabbit ventricular myocytes
loaded with indo-1/AM. Selective inhibitors of Na(+)/H(+) exchange HOE642 (4
isopropyl-3-methyl-sulphonylbenzoyl guanidine methanesulphonate) and KB-R9032 (N
(4-isopropyl-2,2-dimethyl-3-oxo-3, 4-dihydro-2H-benzo-[1,4]oxazine-6-carbonyl)
guanidine methanesulphonate) were used as pharmacological tools for the analysis.
ET-1 at 0.1 nM induced an increase in Ca(2+) transients by 45.6%, while it
increased cell shortening by 109.6%. For a given increase in cell shortening, the
ET-1-induced increase in Ca(2+) transients was much smaller than that induced by
isoprenaline (ISO, 10 nM). Pretreatment with HOE642 and KB-R9032 (1 microM)
inhibited the increase in cell shortening induced by 0.1 nM ET-1 by 51 and 65.
4%, respectively, without a significant alteration of ET-1-induced increase in
Ca(2+) transients. HOE642 and KB-R9032 did not affect baseline levels of cell
shortening and peak Ca(2+) transients, and the effects of ISO (10 nM). These
results indicate that activation of Na(+)/H(+) exchange by ET-1 may play an
important role in the positive inotropic effect and the ET-1-induced increase in
myofilament Ca(2+) sensitivity in rabbit ventricular myocytes.
PMID- 11015319
TI - Cannabinoid receptor-mediated inhibition of acetylcholine release from
hippocampal and cortical synaptosomes.
AB - In previous studies cannabinoid agonists have been found to inhibit and
cannabinoid antagonists to enhance electrically-evoked [(3)H]-acetycholine (ACh)
release in hippocampal slices. The present study was undertaken to determine if
similar cannabinoid effects could be observed in synaptosomes. [(3)H]-ACh release
was evoked by two methods, both sensitive to presynaptic receptor effects. The
first involved the addition of 1.3 mM calcium following perfusion with calcium
free Krebs and the second the addition of 11 mM potassium following perfusion
with normal Krebs. In hippocampal synaptosomes the 1.3 mM calcium-evoked release
and the high potassium-evoked [(3)H]-ACh release were inhibited by the
cannabinoid agonist, WIN 55212-2, by 59 and 39%, respectively, and with an EC(50)
of approximately 1 nM. WIN 55212-2 produced a similar, although less potent,
inhibition of [(3)H]-ACh release in cortical synaptosomes. No inhibitory effect
of WIN 55212-2 on [(3)H]-ACh release in striatal synaptosomes was observed,
supporting previous data collected in this area with brain slices. The
cannabinoid antagonist, SR 141716A, produced a robust enhancement of 1.3 mM
calcium-evoked [(3)H]-ACh release in hippocampal synaptosomes (EC(50)<0.3 nM) but
had no effect on potassium-evoked release or on [(3)H]-ACh release in the cortex
or striatum. In conclusion our data demonstrates the inhibitory effects of WIN
55212-2 observed on ACh release in brain slices can be observed in hippocampal
and cortex synaptosomes, suggesting a direct action of these compounds on the
synaptic terminals. The SR 141716A-induced enhancement of ACh release can
similarly be observed in hippocampal synaptosomes and is probably due to an
inverse agonist action at constitutively active receptors.
PMID- 11015320
TI - Psychometrics of odor quality discrimination: method for threshold determination.
AB - There is no natural physical continuum for odor quality along which an odor
quality discrimination (OQD) threshold can be measured. In an attempt to overcome
this problem, the substitution-reciprocity (SURE) method defines a framework for
the measurement of an OQD threshold. More specifically, it (i) defines a
threshold concept for OQD, including the quantification of qualitative change of
the stimulus, and (ii) suggests how to avoid perceived intensity as an unwanted
cue for discrimination. In doing this, the psychometric properties of odor
quality in the case of eugenol and citral are investigated using both
discrimination (experiment 1) and scaling (experiment 2). Based on discriminatory
responses, a change of approximately one-third in stimulus content was needed to
reach the OQD threshold for eugenol and citral.
PMID- 11015321
TI - Glossopharyngeal taste responses of the channel catfish to binary mixtures of
amino acids.
AB - This study examines the neural processing of binary mixtures in the
glossopharyngeal (IX) taste system of the channel catfish, Ictalurus punctatus,
and finds that the nature of the components of a mixture determines the intensity
of the neural response to it. Taste buds in fish innervated by IX are located
along the gill rakers of the first gill arch and rostral floor of the oral
cavity, and function primarily in the consummatory phase of feeding behavior;
however, few studies of IX taste responses have been reported in any species of
teleost. Here, we report IX taste responses to eight different binary mixtures of
amino acids whose components were adjusted to be approximately equipotent in
electrophysiological recordings. Four binary (group I) mixtures whose components
were indicated from prior electrophysiological cross-adaptation experiments to
bind to independent receptor sites resulted in significantly larger (22% average
increase) integrated IX taste activity than four other (group II) binary mixtures
whose components were indicated to bind to the same or highly cross-reactive
receptor sites. These results are similar to those observed previously from
facial nerve recordings in channel catfish, and to olfactory and taste responses
in other vertebrate and invertebrate species. The group I results help to explain
behavioral observations that chemical mixtures of chemosensory stimuli are often
more stimulatory than their individual components.
PMID- 11015322
TI - Taste preference synergy between glutamate receptor agonists and inosine
monophosphate in rats.
AB - Monosodium glutamate (MSG) elicits a taste called umami and interacts
synergistically with nucleotide monophosphates such as 5'-inosine monophosphate
(IMP) to potentiate this taste intensity. Indeed, the synergistic interaction of
nucleotide monophosphates and MSG is a hallmark of umami. We examined
interactions between MSG and other taste stimuli, including IMP, by measuring the
lick rates of non-deprived rats during 30 s trials. To control for non-linear
psychophysical functions, the concentration of one taste stimulus in a binary
mixture was systematically increased while the concentration of the second taste
stimulus was decreased (stimulus substitution method). Synergy between two
stimuli was detected if the lick rate for a binary mixture exceeded that expected
from the sum of the lick rates for each stimulus alone. In initial experiments,
taste synergy was observed when rats were presented with mixtures of MSG and IMP
but not with mixtures of MSG and sucrose. In subsequent experiments, glutamate
receptor agonists other than MSG were presented with IMP to test for taste
synergy. No evidence of synergy was seen when rats were presented with mixtures
of IMP and kainic acid or IMP and N:-methyl-D-aspartate. However, taste synergy
between IMP and L-AP4, a potent agonist at mGluR4 receptors, was observed. These
results suggest that a metabotropic glutamate receptor similar to mGluR4 may be
involved in the taste synergy that characterizes umami.
PMID- 11015323
TI - Right-nostril dominance in discrimination of unfamiliar, but not familiar,
odours.
AB - In a recent PET study on processing of unfamiliar odours we observed that odour
discrimination performance was superior during right compared with left nostril
presentations, and that mainly the right cerebral hemisphere was activated. In
the present study we investigated whether the asymmetric performance is present
also during the processing of familiar odours. Seventy-one right-handed healthy
subjects (age 21-49 years, 40 females) with normal nasal anatomy and olfactory
thresholds participated. Forty pairs of odours (20 familiar and 20 unfamiliar)
were presented in the same/different paradigm, alternating nostrils and balancing
the order. The number of errors during the discrimination task was compared with
respect to nostril and odour familiarity. The overall odour discrimination
performance was superior on the right side. However, this difference was valid
only for unfamiliar odours, whereas the performance for familiar odours was
symmetrical. Familiar odours were easier to discriminate than unfamiliar ones.
The present data are congruent with the idea of a semantic influence on odour
processing. Odours seem to be processed with a right sided preponderance when not
clearly familiar, and symmetrically when language becomes involved. Future
studies on odour processing should therefore take into account odour familiarity
and side of presentation.
PMID- 11015324
TI - Comprehensive study on G protein alpha-subunits in taste bud cells, with special
reference to the occurrence of Galphai2 as a major Galpha species.
AB - Previous studies have identified many cDNA species that encode a variety of G
protein alpha-subunits occurring in taste buds. These include the cDNA encoding a
taste-bud-specific Galpha, gustducin (G(gust)). Here we carried out comprehensive
analyses of Galpha species that occur in the taste buds of rat circumvallate
papillae and also in their single cells isolated from the taste buds. Reverse
transcriptase-polymerase chain reaction showed the presence of 10 kinds of Galpha
cDNAs, including a splice variant of Galphas, among which G(gust), Galphas,
Galphai2 and Galphai3 cDNAs were shown to be major species. In situ hybridization
and immunohistochemistry showed that Galphai2, as well as G(gust), expressed in a
subset of taste bud cells, and the frequency of Galphai2-expression appears to be
higher than that of G(gust). Southern analyses of the amplified cDNA from single
cells showed that each taste bud cell expresses multiple Galpha mRNA species. For
example, some Galphai2-positive cells also express one or more other Galpha
species, including Galphas, Galphai3 and G(gust), and there is no apparent
correlation in expression among the three Galpha species.
PMID- 11015325
TI - Amino acids dissolved in stream water as possible home stream odorants for masu
salmon.
AB - It is well established that salmon return to their home stream by sensing the
odors of the stream water. In this study we have attempted to identify the home
stream odorants used by masu salmon in Lake Toya. The salmon in Lake Toya return
to the home stream which flows into the lake after lake life for 2-3 years.
Besides water from the home stream, waters from two other streams which flow into
Lake Toya were also used in the experiments. We analyzed the compositions of
amino acids, inorganic cations and bile acids in waters from the three streams.
Application of mixtures of inorganic cations or bile acids, reconstituted based
on the compositions of the stream waters, to the olfactory epithelium induced
only very small responses. On the other hand, application of mixtures of amino
acids induced large responses. The response to artificial stream water
reconstituted based on the compositions of amino acids and salts closely
resembles that to the corresponding stream water. Cross-adaptation experiments
with three combinations of the mixtures were carried out. The response pattern
for each combination closely resembled that to the corresponding combination of
stream waters. Based on the results obtained, we concluded that amino acids
dissolved in the home stream water are possible home stream odorants.
PMID- 11015326
TI - Chemosensory proteins from the proboscis of mamestra brassicae.
AB - Soluble, low molecular weight proteins were immunodetected in proboscis extracts
of Mamestra brassicae males by Western blot, using antibodies raised against the
general odorant-binding protein of the moth Antheraea polyphemus. The same
antibodies weakly labelled the sensillum lymph and subcuticular space of sensilla
styloconica on ultrathin sections of the proboscis. The morphology of sensilla
styloconica is described. The immunodetected proteins yielded several N-terminal
sequences, three of which showed strong affinity for tritiated analogues of
pheromonal compounds of M. brassicae in binding assays. The cDNAs coding for
these sequences were cloned and it was shown that the new proteins are related to
the OS-D protein of Drosophila. They are named chemosensory proteins (CSP-MBRA:A1
CSP-MBRA:A5 and CSP-MBRA:B1 and CSP-MBRA:B2) and may have an odorant-binding
protein-like function. A common localization in both olfaction and taste organs
suggests a physiological role depending on the cellular environment.
PMID- 11015327
TI - Neohesperidin dihydrochalcone is not a taste enhancer in aqueous sucrose
solutions.
AB - Neohesperidin dihydrochalcone (NHDC) is an intensive sweetener, obtained by
alkaline hydrogenation of neohesperidin. In this investigation a supposed taste
enhancing effect of this substance was tested. A three-step procedure was used.
In the first experiment, using a pool of 31 subjects, NHDC and sucrose detection
thresholds were measured. In the second experiment, psychophysical functions for
both tastants were determined. Then, 15 participants closest to the group
threshold who, in addition, had produced monotonic psychophysical taste functions
were selected to participate in the next two experiments. In the third
experiment, taste enhancement was tested. Three psychophysical sucrose functions
were constructed, one with a near-threshold amount of NHDC added to each of seven
sucrose concentrations, one with a near-threshold amount of sucrose added
(control 1) and one without any addition (control 2). No difference was found
between the NHDC-enriched sucrose function and the sucrose-enriched sucrose
function. Finally, in experiment 4, differential threshold functions were
constructed with either NHDC or sucrose added. Neither the overall shape of the
functions nor a comparison of the points of subjective equality showed
enhancement. It was concluded that weak NHDC does not enhance the taste of
aqueous sucrose solutions.
PMID- 11015328
TI - Exposure to behaviourally relevant odour reveals differential characteristics in
rat central olfactory pathways as studied through oscillatory activities.
AB - This study investigated how changes in nutritional motivation modulate odour
related oscillatory activities at several levels of the olfactory pathway in non
trained rats. Local field potential recordings were obtained in freely moving
animals in the olfactory bulb (OB), anterior and posterior parts of the piriform
cortex (APC and PPC respectively) and lateral entorhinal cortex (EC). Dynamic
signal analysis detected changes in power during odour presentation for several
frequency bands The results showed that in most cases odour presentation was
associated with changes in a wide 15-90 Hz frequency band of activity in each
olfactory structure. However, nutritional state modulated initial responses to
food odour (FO) in the OB and EC selectively in the 15-30 Hz frequency band.
Changes in nutritional state also modulated responses to repeated FO stimuli.
Habituation was expressed differentially across structures with a clear
dissociation between the two parts of the piriform cortex. Finally, systemic
injections of scopolamine (0.125 mg/kg) selectively blocked expression of the
nutritional modulation in the OB found in the beta band. These results suggest
that internal state can differentially modulate odour processing among different
olfactory areas and point to a cholinergic-sensitive beta band oscillation during
presentation of a behaviourally meaningful odorant.
PMID- 11015329
TI - Taste function in patients with oral burning.
AB - Burning mouth syndrome (BMS) is an oral pain disorder occurring primarily in post
menopausal women and is frequently accompanied by taste complaints. This
association of symptoms suggests an interaction between the mechanisms of
nociception and gustation, two senses with strong hedonic components. Seventy
three patients of the Taste and Smell Clinic at the University of Connecticut
Health Center who reported experiencing 'unexplained oral burning' were evaluated
for taste function. Both intensity ratings and quality identifications were
measured for a concentration series of sucrose ('sweet'), NaCl ('salty'), citric
acid ('sour') and quinine-HCl ('bitter'). The 57 women with BMS gave lower
intensity ratings to NaCl and sucrose than comparably aged, same sex controls.
Concentrations of NaCl and sucrose >0.10 M were most affected; concentrations of
sucrose and NaCl <0.10 M were rated similarly by BMS and control women. No
intensity differences were found for citric acid or quinine-HCl at any
concentration and no differences were evident between the 16 BMS men and the 14
control men for any stimulus. The BMS women also misidentified the quality of 19%
of the stimuli that were detected whereas control women misidentified 8%. Both
groups detected a similar proportion of stimuli and found lower stimulus
concentrations more difficult to identify than higher concentrations.
Identification of NaCl as 'salty' and citric acid as 'sour' was particularly
difficult for BMS women. The present findings are consistent with the hypothesis
that pain pathway activation may affect neural and behavioral taste function.
PMID- 11015330
TI - The origin of slow potentials on the tongue surface induced by frog
glossopharyngeal efferent fiber stimulation.
AB - When the glossopharyngeal (GP) nerve of the frog was stimulated electrically,
electropositive slow potentials were recorded from the tongue surface and
depolarizing slow potentials from taste cells in the fungiform papillae. The
amplitude of the slow potentials was stimulus strength- and the frequency
dependent. Generation of the slow potentials was not related to antidromic
activity of myelinated afferent fibers in the GP nerve, but to orthodromic
activity of autonomic post-ganglionic C fibers in the GP nerve. Intravenous
injection of atropine abolished the positive and depolarizing slow potentials
evoked by GP nerve stimulation, suggesting that the slow potentials were induced
by the activity of parasympathetic post-ganglionic fibers. The amplitude and
polarity of the slow potentials depended on the concentration of adapting NaCl
solutions applied to the tongue surface. These results suggest that the slow
potentials recorded from the tongue surface and taste cells are due to the liquid
junction potential generated between saliva secreted from the lingual glands by
GP nerve stimulation and the adapting solution on the tongue surface.
PMID- 11015331
TI - Twenty-second annual meeting of the association for chemoreception sciences
PMID- 11015333
TI - Myocardial ischemia and lipoprotein lipase activity.
PMID- 11015334
TI - Fetoscopic direct fetal cardiac access in sheep : An important experimental
milestone along the route to human fetal cardiac intervention.
AB - BACKGROUND: Fetal cardiac interventions by direct ultrasound-guided approaches or
open fetal cardiac surgery have been fraught with technical difficulties, as well
as with significant maternal and fetal morbidity in humans. Therefore, the
purpose of our study in sheep was to assess the feasibility and potential of
fetoscopic direct fetal cardiac access. METHODS AND RESULTS: In 15 anesthetized
pregnant ewes (88 to 109 days of gestation; term, 145 days), 3 to 4 trocars were
percutaneously placed in the uterus. Using videofetoscopic equipment, we assessed
the feasibility of achieving direct fetal cardiac access. Minimally invasive
direct fetal cardiac access by operative fetoscopy was achieved in 10 of the 15
fetal sheep. In 7 fetuses, the approach was successfully tested for fetal cardiac
pacing (n=5) or antegrade fetal cardiac catheterization (n=2). Access was not
achieved in 5 fetuses because of bleeding complications (n=2) or because the
fetoscopic setup could not be established (n=3). All but 2 fetal sheep were alive
at the end of the procedure. Acute fetal demise resulted from maternal
hypotension or kinking of the fetal inferior caval vein by sternal suspension.
Six ewes continued gestation; 3 of these went to term, with a normal fetal
outcome. Two ewes died from septicemia 3 and 7 days after the procedure, and 1
ewe aborted 1 month after the procedure. CONCLUSIONS: Minimally invasive direct
fetal cardiac access by operative fetoscopy is feasible in fetal sheep. The
fetoscopic approach carries important potential for fetal cardiac pacing,
antegrade fetal valvuloplasties, and resection of fetal intrapericardial
teratomas in human fetuses.
PMID- 11015335
TI - Therapeutic angiogenesis with recombinant fibroblast growth factor-2 improves
stress and rest myocardial perfusion abnormalities in patients with severe
symptomatic chronic coronary artery disease.
AB - BACKGROUND: We report the effects of the administration of recombinant fibroblast
growth factor-2 (rFGF-2) protein on myocardial perfusion using single photon
emission computed tomography imaging in humans with advanced coronary disease.
METHODS AND RESULTS: A total of 59 patients with coronary disease that was not
amenable to mechanical revascularization underwent intracoronary (n=45) or
intravenous (n=14) administration of rFGF-2 in ascending doses. Changes in
perfusion were evaluated at baseline and again at 29, 57, and 180 days after rFGF
2 administration. In this uncontrolled study, perfusion scans were analyzed by 2
observers who were blinded to patient identity and test sequence; scans were
displayed in random order, with scans from nonstudy patients randomly
interspersed to enhance blinding. Combining all dose groups, a reduction occurred
in the per-segment reversibility score (reflecting the magnitude of inducible
ischemia) from 1.7+/-0.4 at baseline to 1.1+/-0.6 at day 29 (P:<0.001), 1.2+/-0.7
at day 57 (P:<0.001), and 1.1+/-0.7 at day 180 (P:<0.001). The 37 patients with
evidence of resting hypoperfusion had evidence of improved resting perfusion:
their per-segment rest perfusion score of 1.5+/-0. 5 at baseline decreased to
1.0+/-0.8 at day 29 (P:<0.001), 1.0+/-0.8 at day 57 (P:=0.003), and 1.1+/-0.9 at
day 180 (P:=0.11). CONCLUSIONS: These preliminary data suggest that the
administration of rFGF-2 to patients with advanced coronary disease resulted in
an attenuation of stress-induced ischemia and an improvement in resting
myocardial perfusion; these findings are consistent with a favorable effect of
therapeutic angiogenesis.
PMID- 11015336
TI - Elevated troponin I level on admission is associated with adverse outcome of
primary angioplasty in acute myocardial infarction.
AB - BACKGROUND: In patients with acute myocardial infarction (AMI) undergoing
thrombolytic therapy, an elevated troponin level on admission is associated with
a lower reperfusion rate and a complicated clinical course. Whether an elevated
troponin level on admission similarly predicts an adverse outcome in patients
undergoing primary angioplasty is currently unknown and was investigated in the
present study. METHODS AND RESULTS: Cardiac troponin I (cTnI) was determined on
admission in 110 consecutive patients with AMI associated with ST-segment
elevation or left bundle branch block who underwent primary angioplasty. Fifty
four patients (49%) had an elevated cTnI (>/=0.4 ng/mL) on admission. In patients
with elevated cTnI, primary angioplasty was less likely to achieve TIMI 3 flow
(as classified by the Thrombolysis in Myocardial Infarction trial) in univariate
(76% versus 96%, P:=0.03) or in multivariate (odds ratio 0.1, 95% CI 0.02 to
0.54) analysis. Patients with elevated cTnI were more likely to develop
congestive heart failure (23% versus 9%, P:<0.05) and death, heart failure, or
shock (30% versus 9%, P:=0.006). Elevated cTnI remained a significant predictor
of the composite end point after controlling for other clinical data that were
available early in the course, including time to presentation and angiographic
results (relative risk 5.2, 95% CI 1.03 to 26.3). During a follow-up of 426+/-50
days, elevated admission cTnI was a predictor of cardiac mortality (11% versus
0%, P:=0.012), adverse cardiac events (cardiac mortality or nonfatal
reinfarction; 19% versus 5.4%, P:=0.04), and adverse cardiac events plus target
vessel revascularization (32% versus 14%, P:=0.054). CONCLUSIONS: In patients
with ST-segment elevation AMI, an elevated cTnI on admission is associated with
an increased risk of primary angioplasty failure and a more complicated clinical
course.
PMID- 11015338
TI - Cardiorespiratory fitness and coronary heart disease risk factors: the LDS
Hospital Fitness Institute cohort.
AB - BACKGROUND: Cardiorespiratory fitness is favorably associated with most
modifiable coronary heart disease (CHD) risk factors. Findings are limited,
however, by few data for women, persons with existing CHD, and low-risk
populations. In the present study, we described cross-sectional associations
between cardiorespiratory fitness and CHD risk factors in a large cohort of
middle-aged men and women, of whom the majority were LDS Church members
(Mormons), with and without existing CHD. METHODS AND RESULTS: Comprehensive
health examinations were performed on 3232 men (age 45.9+/-10.8 years) and 1128
women (age 43.8+/-12.8 years) between 1975 and 1997. Maximal treadmill exercise
testing was used to categorize those with (12% of the men and 10% of the women)
and those without CHD into age- and sex-specific cardiorespiratory fitness
quintiles. After adjustments for age, body fat, smoking status, and family
history of CHD, favorable associations were observed between fitness and most CHD
risk factors among men and women, regardless of CHD status. CONCLUSIONS: These
data indicate that enhanced levels of cardiorespiratory fitness may confer
resistance to elevations in CHD risk factors even in a low-risk sample of middle
aged men and women. Furthermore, these findings reinforce current public health
recommendations that advocate increased national levels of physical activity and
cardiorespiratory fitness for primary and secondary CHD prevention.
PMID- 11015337
TI - 17beta-estradiol decreases endothelin-1 levels in the coronary circulation of
postmenopausal women with coronary artery disease.
AB - BACKGROUND: Estrogen reverses acetylcholine-induced coronary vasoconstriction via
the possible facilitation of endothelium-derived NO. Estrogen also affects
endothelium-derived constrictor factors. We therefore investigated the effects of
17beta-estradiol on coronary vasomotor responses to substance P (SP), and
coronary sinus endothelin-1 and NO metabolite levels in postmenopausal women with
coronary heart disease. METHODS AND RESULTS: We studied 20 women; 14 received
estrogen (mean age 65+/-2 years) and 6 served as ethanol control subjects (age
63+/-3 years). Intracoronary infusions of papaverine (8 mg) and SP were
administered before and 20 minutes after 50 pg/min 17beta-estradiol or 0.2
microL/min control. Coronary blood flow was calculated from the diameter, as
measured with quantitative coronary angiography, and flow velocity, as measured
with intracoronary Doppler. Coronary sinus plasma endothelin-1 and
nitrite/nitrate (NO(2)/NO(3)) were measured at baseline, at peak velocity
response to each infusion, and every 5 minutes during the estradiol infusion.
Endothelin-1 levels were decreased after 20 minutes of estradiol (1.12+/-0.18
versus 0.86+/-0.17 pmol/L baseline2 versus estradiol, P:=0.05). Endothelin-1
levels to SP decreased after 17beta-estradiol (1.29+/-0. 18 versus 1.04+/-0.15
and 1.3+/-0.16 versus 0.99+/-0.17 pmol/L for before versus after estradiol, 10
and 25 pmol/min SP; both P:<0.05). NO(2)/NO(3) levels did not change. There was
no change in vasomotor responses to estradiol alone or to papaverine or SP before
versus after estradiol. CONCLUSIONS: Short-term intracoronary 17beta-estradiol
administration decreases coronary endothelin-1 levels. There was no enhancement
of vasomotor responses to SP after the administration of estrogen, suggesting
that the effects of estrogen on coronary acetylcholine responses may be a
specific and not a generalized effect on coronary vasoreactivity.
PMID- 11015339
TI - Lipoprotein lipase activity is associated with severity of angina pectoris.
REGRESS Study Group.
AB - BACKGROUND: Raised triglyceride-rich lipoproteins significantly increase the risk
for cardiovascular disease. Variation in the activity of the enzyme lipoprotein
lipase (LPL), which is crucial in the removal of these lipoproteins, may
therefore modulate this risk. METHODS AND RESULTS: Postheparin levels of LPL
activity and mass were measured in a large cohort of male coronary artery disease
patients participating in the Regression Growth Evaluation Statin Study
(REGRESS), a lipid-lowering regression trial. In addition, the relationships
between LPL activity and mass and severity of angina pectoris according to the
NYHA classification and silent ischemia on 24-hour ambulatory ECG monitoring were
assessed. Patients in different LPL activity quartiles and mass had different
severities of angina; a total of 47% of patients in the lowest LPL quartile
reported class III or IV angina. In contrast, only 29% in the highest activity
quartile (P:=0.002) had severe angina. These parameters were supported by
ambulatory ECG results, for which the total ischemic burden in the lowest LPL
activity quartile was 36. 5+/-104.1 mm x min compared with 14.8+/-38.8 mm x min
in the highest quartile of LPL activity (P:=0.001). LPL activity levels were
strongly correlated with LPL mass (r=0.70, P:<0.0001). A significant association
between the LPL protein mass and NYHA class (P:=0.012) was also demonstrated.
CONCLUSIONS: We have demonstrated a significant relationship between LPL mass and
activity and severity of ischemia as defined by angina class and ambulatory ECG.
These results suggest that LPL influences risk for coronary artery disease by
both catalytic and noncatalytic mechanisms.
PMID- 11015341
TI - Development of antibody against epitope of lipoprotein(a) modified by oxidation:
evaluation of new enzyme-linked immunosorbent assay for oxidized lipoprotein(a).
AB - BACKGROUND: Recently, the biological effects of oxidized lipoprotein(a) [Lp(a)]
have been reported to be more potent than Lp(a), the arteriosclerosis-relevant
lipoprotein. Thus, investigations with oxidized Lp(a) are expected to provide
viewpoints different from the conventional ones based on Lp(a). METHODS AND
RESULTS: An anti-Lp(a) monoclonal antibody (161E2) was produced against synthetic
peptide antigen (Arg-Asn-Pro-Asp-Val-Ala-Pro). This epitope was characterized as
having various properties because its external exposure was induced as a result
of oxidative modification. Using 161E2 antibody, we developed a new enzyme-linked
immunosorbent assay to measure Lp(a) modified by oxidative stress. The present
data demonstrated that oxidized Lp(a) that contains the epitope of 161E2 antibody
was present in the serum of humans. Therefore, we used this new enzyme-linked
immunosorbent assay to evaluate the role of oxidized Lp(a) in patients with
hypertension, which induces oxidative stress. Interestingly, hypertensive
patients with complications showed a significantly higher level of oxidized Lp(a)
in serum than did normotensive subjects (P:<0.01), whereas there was no
significant difference in native Lp(a) between normotensive and hypertensive
subjects. Importantly, positive immunostaining with 161E2 monoclonal antibody was
found in the human arteriosclerotic tissue. CONCLUSIONS: We developed a new
antibody against an epitope in Lp(a) as a result of oxidation treatment but not
in native Lp(a). The present data demonstrated in vivo the presence of oxidized
Lp(a) in the atherosclerotic tissue and its elevation in hypertensive patients.
The presence of oxidized Lp(a) may be important in understanding the role of
Lp(a) in cardiovascular disease.
PMID- 11015340
TI - Association of fibrinogen with cardiovascular risk factors and cardiovascular
disease in the Framingham Offspring Population.
AB - BACKGROUND: Fibrinogen has been identified as an independent risk factor for
cardiovascular disease and associated with traditional cardiovascular risk
factors. Also, the role of elevated fibrinogen in thrombosis suggests that it may
be on the causal pathway for certain risk factors to exert their effect. These
associations remain incompletely characterized. Moreover, the optimal fibrinogen
assay for risk stratification is uncertain. METHODS AND RESULTS: In 2632 subjects
from cycle 5 of the Framingham Offspring Population, fibrinogen levels were
determined with a newly developed immunoprecipitation test (American Biogenetic
Sciences) and the functional Clauss method. With the immunoprecipitation method,
there were significant linear trends across fibrinogen tertiles (P:<0.001) for
age, body mass index, smoking, diabetes mellitus, total cholesterol, HDL
cholesterol, and triglycerides in men and women. The Clauss method had
significant results (P:<0.030), except for triglycerides in men. Fibrinogen
levels were higher for those with compared with those without cardiovascular
disease. After covariate adjustment, fibrinogen remained significantly higher in
those with cardiovascular disease with the use of the immunoprecipitation test
(P:=0.035 and P:=0.018 for men and women, respectively) but not with the Clauss
method. CONCLUSIONS: Fibrinogen was associated with traditional cardiovascular
risk factors. Elevation of fibrinogen may provide a mechanism for risk factors to
exert their effect. Also, fibrinogen levels were higher among subjects with
cardiovascular disease compared with those without disease. The
immunoprecipitation test showed a stronger association with cardiovascular
disease than the Clauss method, suggesting that it may be a useful screening tool
to identify individuals at increased thrombotic risk.
PMID- 11015342
TI - Homozygosity for 807 T polymorphism in alpha(2) subunit of platelet
alpha(2)beta(1) is associated with increased risk of cardiovascular mortality in
high-risk women.
AB - BACKGROUND: Platelet adhesion to collagen is the initial step in both hemostasis
and thrombosis; this adhesion is mediated by alpha(2)beta(1) on the surface of
platelet membranes. An 807 C to T single nucleotide exchange polymorphism close
to the gene coding for the alpha(2) subunit of alpha(2)beta(1) is associated with
the density of alpha(2)beta(1) on the platelet membrane. METHODS AND RESULTS: We
studied the relation of the alpha(2)beta(1) 807 C/T genotype to cardiovascular
mortality in a prospective cohort study of 12 239 women who were invited for the
breast cancer screening program of Utrecht, the Netherlands. The initial age was
between 52 and 67 years. Women were followed on vital status between 1976 and
1995 (168 513 women-years). Data were analyzed by using a nested case-control
design. The alpha(2)beta(1) 807 C/T genotype was not associated with
cardiovascular mortality in the total population: the rate ratio for
cardiovascular mortality in 807 TT homozygotes compared with 807 CC wild types
was 1.2 (95% CI 0.8 to 1.7). However, the alpha(2)beta(1) 807 T polymorphism was
associated with an increased risk of cardiovascular mortality in women who smoked
or in women who had indications of compromised endothelium, such as diabetes and
microalbuminuria. In those who were exposed to >/=2 of these factors, the risk
ratio (95% CI) between alpha(2)beta(1) 807 TT homozygotes and 807 CC wild types
was 14.1 (5.0 to 39.9). CONCLUSIONS: alpha(2)beta(1) 807 TT homozygosity, coding
for increased alpha(2)beta(1) density on the platelet membrane, is associated
with an increased risk of cardiovascular mortality in those women with
indications of compromised endothelium.
PMID- 11015343
TI - Time to presentation with acute myocardial infarction in the elderly:
associations with race, sex, and socioeconomic characteristics.
AB - BACKGROUND: Although prompt treatment is a cornerstone of the management of acute
myocardial infarction (AMI), prior studies have shown that one fourth of AMI
patients arrive at the hospital >6 hours after symptom onset. It would be
valuable to identify individuals at highest risk for late arrival, but
predisposing factors have yet to be fully characterized. METHODS AND RESULTS:
Data from the Cooperative Cardiovascular Project, involving Medicare
beneficiaries aged >65 years hospitalized between January 1994 and February 1996
with confirmed AMI, were used to identify patients who presented "late" (>/=6
hours after symptom onset). Patient characteristics were tested for associations
with late presentation by use of backward stepwise logistic regression. Among 102
339 subjects, 29.4% arrived late. Significant predictors of late arrival (odds
ratio, 95% CI) included diabetes (1.11, 1.07 to 1.14) and a history of angina
(1.32, 1.28 to 1.35), whereas prior MI (0.82, 0.79 to 0.85), prior angioplasty
(0.80, 0.75 to 0.85), prior bypass surgery (0.93, 0.89 to 0.98), and cardiac
arrest (0.52, 0.46 to 0. 58) predicted early presentation. Additionally, initial
evaluation at an outpatient clinic (2.63, 2.51 to 2.75) and daytime presentation
(1.67, 1.59 to 1.72) predicted late arrival. Finally, female sex, black race, and
poverty, which were evaluated with an 8-level race-sex-socioeconomic status
interaction term, were also risk factors for delay. CONCLUSIONS: Delayed hospital
presentation is a common problem among Medicare beneficiaries with AMI. Factors
associated with delay include not only clinical and logistical issues but also
race, sex, and socioeconomic characteristics. Education efforts designed to
hasten AMI treatment should be directed at individuals with risk factors for late
arrival.
PMID- 11015344
TI - Feasibility of a novel blood noise reduction algorithm to enhance reproducibility
of ultra-high-frequency intravascular ultrasound images.
AB - BACKGROUND: Ultra-high-frequency (40- to 50-MHz) intravascular ultrasound (IVUS)
improves image quality compared with conventional 20- to 30-MHz IVUS. However, as
the frequency of IVUS increases, high-intensity backscatter from blood components
may cause visual difficulties in discrimination between the lumen and arterial
wall structure. The purpose of this study was to evaluate the effect of a novel
blood noise reduction algorithm (BNR) on quantitative coronary ultrasound
measurements. METHODS AND RESULTS: IVUS studies using a 40-MHz transducer were
performed in 35 patients with coronary artery disease. A total of 620 gray-scale
images (310 pairs) were processed with and without the BNR, and lumen cross
sectional area (CSA) was determined by 2 independent observers. With the BNR, the
intraobserver and interobserver correlation coefficients for lumen CSA were
significantly improved (0.85 to 0.99 and 0.80 to 0.98, respectively). In the 270
images (135 pairs) in which vessel wall measurements were possible, the BNR
significantly improved the intraobserver and interobserver correlation
coefficients for plaque plus media CSA (0.83 to 0.99 and 0.76 to 0.97,
respectively), whereas no influence was observed for external elastic membrane
CSA (1.00 to 1.00 and 0.99 to 0.99, respectively). CONCLUSIONS: This study
demonstrates the feasibility of this novel algorithm to reduce blood noise,
thereby enabling accurate lumen border delineation and providing reproducible
measurements of both the lumen and plaque plus media CSAs. Incorporating a
digital BNR may serve as an important adjunct to ultra-high-frequency IVUS
imaging for improving accurate quantitative evaluation of vessel dimensions.
PMID- 11015345
TI - Mechanisms of discordant alternans and induction of reentry in simulated cardiac
tissue.
AB - BACKGROUND: T-wave alternans, which is associated with the genesis of cardiac
fibrillation, has recently been related to discordant action potential duration
(APD) alternans. However, the cellular electrophysiological mechanisms
responsible for discordant alternans are poorly understood. METHODS AND RESULTS:
We simulated a 2D sheet of cardiac tissue using phase 1 of the Luo-Rudy cardiac
action potential model. A steep (slope >1) APD restitution curve promoted
concordant APD alternans and T-wave alternans without QRS alternans. When pacing
was from a single site, discordant APD alternans occurred only when the pacing
rate was fast enough to engage conduction velocity (CV) restitution, producing
both QRS and T-wave alternans. Tissue heterogeneity was not required for this
effect. Discordant alternans markedly increases dispersion of refractoriness and
increases the ability of a premature stimulus to cause localized wavebreak and
induce reentry. In the absence of steep APD restitution and of CV restitution,
sustained discordant alternans did not occur, but reentry could be induced if
there was marked electrophysiological heterogeneity. Both discordant APD
alternans and preexisting APD heterogeneity facilitate reentry by causing the
waveback to propagate slowly. CONCLUSION: Discordant alternans arises dynamically
from APD and CV restitution properties and markedly increases dispersion of
refractoriness. Preexisting and dynamically induced (via restitution) dispersion
of refractoriness independently increase vulnerability to reentrant arrhythmias.
Reduction of dynamically induced dispersion by appropriate alteration of
electrical restitution has promise as an antiarrhythmic strategy.
PMID- 11015346
TI - Effect of renal artery stenting on renal function and size in patients with
atherosclerotic renovascular disease.
AB - BACKGROUND: Renal artery stenting is widely performed, but little is known about
its effectiveness in preserving renal function and size in patients with
renovascular disease and chronic renal insufficiency. We studied the effect of
renal artery stenting on renal function and size in patients with obstructive
renovascular disease and chronic renal insufficiency. METHODS AND RESULTS: Stent
deployment was performed in patients with chronic renal insufficiency (creatinine
>1.5 mg. dL(-1)) and global renovascular obstruction (bilateral renal artery
stenosis or unilateral stenosis in the presence of a solitary or single
functional kidney). The effect of renal artery stenting on renal function was
assessed by comparing the slopes of the regression lines derived from the
reciprocal of serum creatinine versus time plotted before and after stent
deployment. Renal size was assessed by serial ultrasound of pole-to-pole kidney
length. Stenting was successful in all 61 vessels in 33 patients. Twenty-five
patients had complete follow-up (mean 20+/-11 months). Before stent deployment,
all patients exhibited a negative slope, indicating progressive renal
insufficiency. After stent deployment, the slopes were positive in 18 and less
negative in 7 patients. Thus, the mean slope increased from -0.0079 to 0.0043 dL.
mg(-1). mo(-1) (P:<0.001). Ultrasonography on 41 kidneys revealed preservation of
size, with the kidney length measuring 10.4+/-1.4 cm at baseline and 10.4+/-1.1
cm at last follow-up (P:=NS). Patient survival at 20+/-11 months was 90%.
CONCLUSIONS: In patients with chronic renal insufficiency and global obstructive
atherosclerotic renovascular disease, renal artery stenting improves or
stabilizes renal function and preserves kidney size.
PMID- 11015347
TI - Early assessment of myocardial salvage by contrast-enhanced magnetic resonance
imaging.
AB - BACKGROUND: Myocardial salvage after acute myocardial infarction is defined
clinically by early restoration of flow and long-term improvement in contractile
function. We hypothesized that contrast-enhanced magnetic resonance imaging
(MRI), performed early after myocardial infarction, indexes myocardial salvage.
We studied the relationship between the transmural extent of hyperenhancement by
contrast-enhanced MRI, restoration of flow, and recovery of function. METHODS AND
RESULTS: The left anterior descending coronary artery was occluded in dogs (n=15)
for either 45 minutes, 90 minutes, or permanently. Cine and contrast-enhanced MRI
were performed 3 days after the procedure; cine MRI was also done 10 and 28 days
after the procedure. The transmural extent of hyperenhancement and wall
thickening were determined using a 60-segment model. The mean transmural extent
of hyperenhancement for the 45-minute occlusion group was 22% of the 90-minute
group and 18% of the permanent occlusion group (P:<0.05 for both). The transmural
extent of hyperenhancement on day 3 was related to future improvement in both
wall thickening score and absolute wall thickening at 10 and 28 days (P:<0.0001
for each). For example, of the 415 segments on day 3 that were dysfunctional and
had <25% transmural hyperenhancement, 362 (87%) improved by day 28. Conversely,
no segments (0 of 9) with 100% hyperenhancement improved. The transmural extent
of hyperenhancement on day 3 was a better predictor of improvement in contractile
function than occlusion time (P:<0.0001). CONCLUSIONS: A reduction in the
transmural extent of hyperenhancement by contrast-enhanced MRI early after
myocardial infarction is associated with an early restoration of flow and future
improvement in contractile function.
PMID- 11015348
TI - Inhibitory effect of angiotensin II type 2 receptor on coronary arterial
remodeling after aortic banding in mice.
AB - BACKGROUND: The renin-angiotensin system is thought to be critical for the
development of cardiac hypertrophy, whereas the role of the angiotensin II type 2
(AT(2)) receptor in the process is not defined. Using the AT(2) receptor-null
(Agtr2-) mouse, we tested the hypothesis that the AT(2) receptor could exert an
antigrowth effect in cardiac hypertrophy. METHODS AND RESULTS: Cardiac
hypertrophy was induced by suprarenal abdominal aortic banding in 10- to 12-week
old Agtr2- and wild-type (Agtr2+) mice for 6 or 12 weeks. Carotid arterial
pressure was not different between the strains, although aortic banding increased
arterial pressure by approximately 40 mm Hg. Aortic banding increased the heart
weight/body-weight ratio and the cross-sectional area of cardiomyocytes by 15%,
resulting in comparable cardiomyocyte hypertrophy in the 2 strains. In contrast,
coronary arterial thickening and perivascular fibrosis, determined by the
media/lumen-area ratio and the collagen/vessel-area ratio, respectively, were 50%
greater in Agtr2- than in Agtr2+ mice after banding, whereas these parameters
were similar in sham-operated mice. Radioligand binding studies using the whole
heart and immunohistochemistry showed that AT(2) receptor expression was limited
and localized in the coronary artery and perivascular region. CONCLUSIONS: These
results suggest that the AT(2) receptor mediates an inhibitory effect on coronary
arterial remodeling, such as medial hypertrophy and perivascular fibrosis in
response to pressure overload, and an activation of the renin-angiotensin system.
PMID- 11015349
TI - Cardiac-specific overexpression of tumor necrosis factor-alpha causes oxidative
stress and contractile dysfunction in mouse diaphragm.
AB - BACKGROUND: We have developed a transgenic mouse with cardiac-restricted
overexpression of tumor necrosis factor-alpha (TNF-alpha). These mice develop a
heart failure phenotype characterized by left ventricular dysfunction and
remodeling, pulmonary edema, and elevated levels of TNF-alpha in the peripheral
circulation from cardiac spillover. Given that TNF-alpha causes atrophy and loss
of function in respiratory muscle, we asked whether transgenic mice developed
diaphragm dysfunction and whether contractile losses were caused by oxidative
stress or tissue remodeling. METHODS AND RESULTS: muscles excised from transgenic
mice and littermate controls were studied in vitro with direct electrical
stimulation. Cytosolic oxidant levels were measured with 2', 7'
dichlorofluorescin diacetate; emissions of the oxidized product were detected by
fluorescence microscopy. Force generation by the diaphragm of transgenic animals
was 47% less than control (13.2+/-0. 8 [+/-SEM] versus 25.1+/-0.6 N/cm(2);
P:<0.001); this weakness was associated with greater intracellular oxidant levels
(P:<0.025) and was partially reversed by 30-minute incubation with the
antioxidant N:-acetylcysteine 10 mmol/L (P:<0.01). Exogenous TNF-alpha 500
micromol/L increased oxidant production in diaphragm of wild-type mice and caused
weakness that was inhibited by N:-acetylcysteine, suggesting that changes
observed in the diaphragm of transgenic animals were mediated by TNF-alpha. There
were no differences in body or diaphragm weights between transgenic and control
animals, nor was there evidence of muscle injury or apoptosis. CONCLUSIONS:
Elevated circulating levels of TNF-alpha provoke contractile dysfunction in the
diaphragm through an endocrine mechanism thought to be mediated by oxidative
stress.
PMID- 11015350
TI - Direct evidence for cytokine involvement in neointimal hyperplasia.
AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1) are
proximal inflammatory cytokines that stimulate expression of adhesion molecules
and induce synthesis of other proinflammatory cytokines. In addition, TNF-alpha
and IL-1 influence vascular smooth muscle cell migration and proliferation in
vitro. In view of the inflammatory nature of neointimal hyperplasia (NIH), we
tested the hypothesis that endogenous TNF-alpha and IL-1 modulate low shear
stress-induced NIH. METHODS AND RESULTS: Mice underwent unilateral common carotid
artery (CCA) ligation. Low shear stress in the patent ligated CCA has previously
been shown to result in remodeling and NIH. Reverse transcriptase-polymerase
chain reaction for TNF-alpha and IL-1alpha mRNA demonstrated both TNF-alpha and
IL-1alpha mRNA in ligated CCAs, whereas normal and sham-operated CCAs had none.
Mice lacking functional TNF-alpha (TNF-/-) developed 14-fold less neointimal area
than WT controls (P:<0.05). p80 IL-1 type I receptor knockout (IL-1RI-/-) mice
tended to develop less (7-fold, P:>0.05) neointimal area than WT controls.
Furthermore, no IL-1alpha mRNA expression was detected in CCAs from TNF-/- mice;
however, TNF-alpha mRNA expression was found in the IL-1RI-/- mice. Mice that
overexpress membrane-bound TNF-alpha but produce no soluble TNF-alpha display an
accentuated fibroproliferative response to low shear stress (P:<0.05).
CONCLUSIONS: These results directly demonstrate that TNF-alpha and IL-1 modulate
NIH induced by low shear stress. NIH can proceed by way of soluble TNF-alpha
independent mechanisms. Specific anti-TNF-alpha and anti-IL-1 therapies may
lessen NIH.
PMID- 11015351
TI - Confocal microscopic localization of constitutive and heat shock-induced proteins
HSP70 and HSP27 in the rat heart.
AB - BACKGROUND: Heat-shock treatment of rats elevates expression of heat-shock
proteins, which play a role in improving the contractile recovery and reducing
infarct size in hearts after ischemic injury. However, the location of these
proteins in the heart is unknown. METHODS AND RESULTS: Anesthetized rats were
heat-shocked by elevation of body temperature to 42 degrees C to 42.5 degrees C
for 15 minutes, followed by 24 hours of recovery. Control and heat-shocked hearts
were extirpated and perfused briefly with saline followed by 2% paraformaldehyde
in PBS. Confocal immunofluorescence microscopy of control hearts revealed that
HSP27 was localized in cardiomyocytes in a pattern reminiscent of Z bands and was
colocalized with neuronal markers in somata and axons. No obvious change in HSP27
content or distribution occurred after heat shock. Confocal microscopy revealed
little or no HSP70 in control hearts. After heat shock, HSP70 was detected
neither in cardiomyocytes nor in neuronal elements within the heart, but HSP70
was abundant in small blood vessels found between the ventricular cardiomyocytes.
CONCLUSIONS: Heat shock induces a cell type-specific expression of HSP70 in blood
vessels but not myocytes or intrinsic cardiac neurons, suggesting that blood
vessels play a primary role in myocardial protection.
PMID- 11015352
TI - Roles of P-selectin in inflammation, neointimal formation, and vascular
remodeling in balloon-injured rat carotid arteries.
AB - BACKGROUND: P-selectin plays key roles in mediating inflammation through
promoting adherence of leukocytes to activated platelets and endothelium. This
process is one of the initial events in atherosclerosis and restenosis after
coronary angioplasty. METHODS AND RESULTS: Using a rat balloon-injury model, we
examined the role of P-selectin in vascular inflammatory processes. In the acute
phase, immunohistochemistry revealed that P-selectin was intensely expressed on
both activated platelets covering the denuded segment and endothelial cells of
the inflamed adventitial small vessels. Treatment with an anti-P-selectin
monoclonal antibody (MAb) for 8 consecutive days significantly inhibited
neointimal formation at day 14 (42% inhibition; P:<0.05), and this effect
persisted at day 56 (40% inhibition; P:<0.01) compared with the control group.
Vascular shrinking accompanying adventitial fibrosis was also attenuated at day
56. Inhibition of both neointimal formation and vascular shrinking resulted in
the lumen area of the anti-P-selectin treatment group being approximately 3 times
larger at day 56 than that of the control group. Accumulation of CD45-positive
leukocytes in the developing neointima, media, and adventitia at day 8 was
significantly inhibited by treatment with the anti-P-selectin MAb. Scanning
electron microscopy demonstrated that anti-P-selectin treatment resulted in a
less thrombogenic surface of the arterial intima, which featured a
pseudoendothelial appearance at day 14 after injury. CONCLUSIONS: These results
suggest that inhibition of P-selectin-mediated leukocyte recruitment prevents the
development of neointimal formation, adventitial inflammation, and vascular
shrinking and promotes pseudoendothelialization by luminal smooth muscle cells.
This treatment thus beneficially affects vascular remodeling after balloon injury
in rats.
PMID- 11015354
TI - Unilateral Vineberg arterial graft with a patency of 30 years.
PMID- 11015353
TI - Secondary pulmonary hypertension in chronic heart failure: the role of the
endothelium in pathophysiology and management.
AB - Pulmonary vascular resistance is frequently elevated in patients with chronic
left ventricular failure as a result of dysregulation of vascular smooth muscle
tone and structural remodeling. The former is reversible over a period of minutes
to days by pharmacological vasodilators, whereas the latter is relatively fixed
and may resolve only slowly, over months to years. These abnormalities are due,
at least in part, to pulmonary vascular endothelial dysfunction that results in
impaired nitric oxide availability and increased endothelin expression. In
patients with chronic heart failure, the resulting pulmonary hypertension
directly affects right ventricular function and may affect exercise capacity,
morbidity, and mortality. New treatment strategies, which include the use of
agents that increase nitric oxide availability or oppose the actions of
endothelin, may improve the structure and function of the pulmonary vasculature
in patients with chronic heart failure.
PMID- 11015355
TI - American College of Cardiology/American Heart Association Clinical Competence
Statement on Stress Testing. A Report of the American College of
Cardiology/American Heart Association/American College of Physicians-American
Society of Internal Medicine Task Force on Clinical Competence.
PMID- 11015357
TI - Defibrillator disagreement.
PMID- 11015356
TI - Visualization of automatic implantable cardioverter-defibrillator patches using
electron beam angiography.
PMID- 11015358
TI - Multicenter evaluation of epidemiological typing of methicillin-resistant
Staphylococcus aureus strains by repetitive-element PCR analysis. The European
Study Group on Epidemiological Markers of the ESCMID.
AB - Rapid and efficient epidemiologic typing systems would be useful to monitor
transmission of methicillin-resistant Staphylococcus aureus (MRSA) at both local
and interregional levels. To evaluate the intralaboratory performance and
interlaboratory reproducibility of three recently developed repeat-element PCR
(rep-PCR) methods for the typing of MRSA, 50 MRSA strains characterized by pulsed
field gel electrophoresis (PFGE) (SmaI) analysis and epidemiological data were
blindly typed by inter-IS256, 16S-23S ribosomal DNA (rDNA), and MP3 PCR in 12
laboratories in eight countries using standard reagents and protocols.
Performance of typing was defined by reproducibility (R), discriminatory power
(D), and agreement with PFGE analysis. Interlaboratory reproducibility of pattern
and type classification was assessed visually and using gel analysis software.
Each typing method showed a different performance level in each center. In the
center performing best with each method, inter-IS256 PCR typing achieved R = 100%
and D = 100%; 16S-23S rDNA PCR, R = 100% and D = 82%; and MP3 PCR, R = 80% and D
= 83%. Concordance between rep-PCR type and PFGE type ranged by center: 70 to 90%
for inter-IS256 PCR, 44 to 57% for 16S-23S rDNA PCR, and 53 to 54% for MP3 PCR
analysis. In conclusion, the performance of inter-IS256 PCR typing was similar to
that of PFGE analysis in some but not all centers, whereas other rep-PCR
protocols showed lower discrimination and intralaboratory reproducibility. None
of these assays, however, was sufficiently reproducible for interlaboratory
exchange of data.
PMID- 11015359
TI - Relevance of CagA positivity to clinical course of Helicobacter pylori infection
in children.
AB - A potential virulence determinant of Helicobacter pylori is the cagA gene
product. To determine the relevance of the expression of CagA to the clinical
picture and outcome of H. pylori infection in children, we examined 104
consecutive children diagnosed with H. pylori infection. Serum samples were
collected to test for the presence of immunoglobulin G (IgG) anti-CagA
antibodies. Forty-five patients (43%) had antibodies to the CagA protein (group
I), and 59 did not (group II). Seropositive patients had a longer prediagnostic
history of abdominal pain (P = 0.02), more severe abdominal pain (defined as
ulcer pain) (P = 0.05), a higher prevalence of duodenal ulcer (38 versus 7%;
P<0.01), more active chronic gastritis (82 versus 32%; P<0.001), and a higher
titer of serum IgG anti-H. pylori antibodies (P<0.001). Ninety percent of the
patients were monitored for 27+/-18 months. On multivariate analysis, CagA
negative patients had a 3.8-fold-higher chance of achieving a disease-free state
than CagA-positive patients (95% confidence interval, 1.5- to 9.5-fold). We
conclude that infection with CagA-producing strains of H. pylori is a risk factor
for severe clinical disease and ongoing infection.
PMID- 11015361
TI - Multicenter evaluation of AMPLICOR and automated COBAS AMPLICOR CT/NG tests for
Neisseria gonorrhoeae.
AB - The fully automated COBAS AMPLICOR CT/NG and semiautomated AMPLICOR CT/NG tests
were evaluated in a multicenter trial for their ability to detect Neisseria
gonorrhoeae infections. Test performance compared to that of culturing was
evaluated for 2,192 matched endocervical swab and urine specimens obtained from
women and for 1, 981 matched urethral swab and urine specimens obtained from men.
Culture-negative, PCR-positive specimens that tested positive in a confirmatory
PCR test for an alternative target sequence within the N. gonorrhoeae 16S rRNA
gene were considered to be true positives. The overall prevalences of gonorrhea
were 6.6% in women and 20.1% in men. The COBAS AMPLICOR and AMPLICOR formats
yielded concordant results for 98.8% of the specimens and exhibited virtually
identical sensitivities and specificities. The results that follow are for the
COBAS AMPLICOR format. With the infected patient as the reference standard, the
resolved sensitivities of PCR were 92.4% for endocervical swab specimens and
64.8% for female urine specimens. There were no significant differences in these
rates between women with and without symptoms. Among symptomatic men, COBAS
AMPLICOR sensitivities were 94.1% for urine and 98.1% for urethral swabs; for
asymptomatic men, the results were 42.3 and 73.1%, respectively. In comparison,
the sensitivities of culturing were 84.8% for endocervical specimens, 92.7% for
symptomatic male urethral specimens, and only 46.2% for urethral specimens
obtained from asymptomatic men. When PCR results were analyzed as if only a
single test had been performed on a single specimen type, the resolved
sensitivity was always higher. The resolved specificities of PCR were 99.5% for
endocervical swab specimens, 99.8% for female urine specimens, 98.9% for male
urethral swab specimens, and 99.9% for male urine specimens. The internal control
revealed that 2.1% of specimens were inhibitory when initially tested.
Nevertheless, valid results were obtained for 99.2% of specimens because 60.0% of
the inhibitory specimens were not inhibitory when a second aliquot was tested.
The COBAS AMPLICOR CT/NG test for N. gonorrhoeae exhibited high sensitivity and
specificity with urethral swab and urine specimens from men and endocervical swab
specimens from women and thus is well suited for diagnosing and screening for N.
gonorrhoeae infection.
PMID- 11015360
TI - Characterization of enterovirus isolates from patients with heart muscle disease
in a selenium-deficient area of China.
AB - An association of enterovirus infection with endemic cardiomyopathy (Keshan
disease [KD]) and outbreaks of myocarditis in selenium-deficient rural areas of
southwestern China has been established. Enteroviruses have been isolated from
patients with KD or during outbreaks of myocarditis in last two decades. Six of
these isolates grew readily in cell lines (Vero or HEp-2) and were investigated
by a novel molecular typing method apart from serotyping and pathogenicity. A
neutralization assay identified two isolates from KD as coxsackievirus serotype
B2 (CVB2) and two isolates from myocarditis as coxsackievirus serotype B6 (CVB6)
but failed to type the remaining two isolates, also from myocarditis. Direct
nucleotide sequencing of reverse transcription-PCR products amplified from the 5'
nontranslated region (5'NTR) of these viruses confirmed that they belong to a
phylogenetic cluster consisting of coxsackie B-like viruses, including some
echovirus serotypes. Sequence analysis of the coding region for viral capsid
protein VP1 showed that two isolates serotyped as CVB2 have the highest amino
acid sequence homology with CVB2 and that the remaining four isolates, two CVB6
and the two unknown serotypes, are most closely related to the sequence of CVB6.
Sequences among these isolates varied from 82.3 to 99% in the 5'NTR and from 69
to 99% in VP1, indicating no cross contamination. The pathogenicity of these
viruses in adult and suckling mice was assessed. None caused pathologic changes
in the hearts of adult MF-1 or SWR mice, although pancreatitis was evident.
However, the four CVB6-like viruses caused death in suckling mice, similar to a
virulent coxsackievirus group B3 laboratory strain. In conclusion, the sequence
data confirm that coxsackievirus group B serotypes are predominant in the region
in which KD is endemic and may be the etiological agents in outbreaks of
myocarditis. VP1 genotyping of enteroviruses is accurate and reliable. Animal
experiments indicate that isolates may differ in pathogenicity.
PMID- 11015362
TI - Diarrheagenic Escherichia coli and acute and persistent diarrhea in returned
travelers.
AB - To determine the role of diarrheagenic Escherichia coli in acute and persistent
diarrhea in returned travelers, a case control study was performed.
Enterotoxigenic E. coli (ETEC) was detected in stool samples from 18 (10.7%) of
169 patients and 4 (3.7%) of 108 controls. Enteroaggregative E. coli (EAggEC) was
detected in 16 (9.5%) patients and 7 (6.5%) controls. Diffuse adherent E. coli
strains were commonly present in both patients (13%) and controls (13.9).
Campylobacter and Shigella species were the other bacterial enteropathogens most
commonly isolated (10% of patients, 2% of controls). Multivariate analysis showed
that the presence of ETEC was associated with acute diarrhea (odds ratio [OR],
6.7; 95% confidence interval [CI], 1.5 to 29.1; P = 0.005), but not with
persistent diarrhea (OR, 1.6; 95% CI, 0.4 to 7.4). EAggEC was significantly more
often present in patients with acute diarrhea than in controls (P = 0.009), but
no significant association remained after multivariate analysis. ETEC and EAggEC
are frequently detected in returned travelers with diarrhea. The presence of ETEC
strains is associated with acute but not with persistent diarrhea.
PMID- 11015363
TI - Brachyspira aalborgi infection diagnosed by culture and 16S ribosomal DNA
sequencing using human colonic biopsy specimens.
AB - In this study we report on the isolation and characterization of the intestinal
spirochete Brachyspira aalborgi using human mucosal biopsy specimens taken from
the colon of a young adult male with intestinal spirochetosis. A selective
medium, containing 400 microg of spectinomycin/ml and 5 microg of polymyxin/ml
was used for the isolation procedure. A high degree of similarity, in terms of
phenotypic properties and 16S ribosomal DNA sequence, was observed between the
isolated strain, named W1, and the type strain, 513A, of B. aalborgi. A
similarity of 99.7% in the nucleotide sequence was found between W1 and 513A(T),
based on the almost-complete gene. A short segment of the 16S rRNA gene was
amplified by PCR using genetic material enriched from paraffin-embedded biopsy
specimens, which were taken from the patient on two occasions. The products
showed 16S rRNA gene sequences virtually identical to that of strain 513A(T) in
the actual region. Immunohistochemistry was performed on the colonic biopsy
specimens with a polyclonal antibody raised against an intestinal spirochete
isolated in a previous case of human intestinal spirochetosis. The antibody
reacted strongly with the spirochete on the luminal epithelium. No immune
reaction was seen within or below the surface epithelium. Routine histology did
not reveal signs of colitis. Electron microscopy showed spirochetes attached end
on to the colonic mucosal surface. The isolate grew poorly on a commonly used
selective medium for intestinal spirochetes, which may explain previous failures
to isolate B. aalborgi.
PMID- 11015364
TI - Serodiagnosis of Louse-Borne relapsing fever with glycerophosphodiester
phosphodiesterase (GlpQ) from Borrelia recurrentis.
AB - Human louse-borne relapsing fever occurs in sporadic outbreaks in central and
eastern Africa that are characterized by significant morbidity and mortality.
Isolates of the causative agent, Borrelia recurrentis, were obtained from the
blood of four patients during a recent epidemic of the disease in southern Sudan.
The glpQ gene, encoding glycerophosphodiester phosphodiesterase, from these
isolates was sequenced and compared with the glpQ sequences obtained from other
relapsing-fever spirochetes. Previously we showed that GlpQ of Borrelia hermsii
is an immunogenic protein with utility as a serological test antigen for
discriminating tick-borne relapsing fever from Lyme disease. In the present work,
we cloned and expressed the glpQ gene from B. recurrentis and used recombinant
GlpQ in serological tests. Acute- and convalescent-phase serum samples obtained
from 42 patients with louse-borne relapsing fever were tested with an indirect
immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA)
that used whole cells of B. recurrentis and with immunoblotting to whole-cell
lysates of the spirochete and Escherichia coli producing recombinant GlpQ. The
geometric mean titers of the acute- and convalescent-phase serum samples measured
by IFA were 1:83 and 1:575, respectively. The immunoblot analysis identified a
high level of reactivity and seroconversion to GlpQ, and the assay was more
sensitive than the whole-cell IFA and ELISA using purified, recombinant histidine
tagged GlpQ. Serum antibodies to GlpQ and other antigens persisted for 27 years
in one patient. We conclude that assessment of anti-GlpQ antibodies will allow
serological confirmation of louse-borne relapsing fever and determination of
disease prevalence.
PMID- 11015366
TI - Evaluation of the MicroScan rapid neg ID3 panel for identification of
Enterobacteriaceae and some common gram-negative nonfermenters.
AB - The MicroScan Rapid Neg ID3 panel (Dade Behring, Inc., West Sacramento, Calif.)
is designed for the identification of gram-negative bacilli. We evaluated its
ability to accurately identify Enterobacteriaceae that are routinely encountered
in a clinical laboratory and glucose nonfermenting gram-negative bacilli. Using
511 stock cultures that were maintained at -70 degrees C and passaged three times
before use, we inoculated panels according to the manufacturer's instructions and
processed them in a Walk/Away instrument using version 22.01 software. The time
to identification was 2 h and 30 min. All panel identifications were compared to
reference identifications previously determined by conventional tube
biochemicals. At the end of the initial 2.5-h incubation period, 405 (79.3%)
identifications were correct. An additional 49 (9.6%) isolates were correctly
identified after required additional off-line biochemical tests were performed.
Thus, at 24 h, 88.8% of the 511 strains tested were correctly identified. Twenty
two (4.3%) were identified to the genus level only. Twenty-six (5.1%) strains
were misidentified. Because the system is based on fluorogenics, there are no
conventional tests readily available with which to compare possibly incorrect
reactions. Of the 28 Salmonella strains that were tested, 5 were incorrectly
reported. The 21 remaining errors were scattered among the genera tested. Testing
on nine strains gave a result of "no identification" (very rare biotype). The
Rapid Neg ID3 panel in this study approached 89% accuracy for the identification
of gram-negative organisms encountered in the hospital laboratory.
PMID- 11015365
TI - Spoligotyping and polymorphic GC-rich repetitive sequence fingerprinting of
mycobacterium tuberculosis strains having few copies of IS6110.
AB - Several genetic loci have been utilized to genotype isolates of Mycobacterium
tuberculosis. A shortcoming of the most commonly used method, IS6110
fingerprinting, is that it does not adequately discriminate between isolates
having few copies of IS6110. This study was undertaken to compare pTBN12
fingerprinting of polymorphic GC-rich repetitive sequence genes and spoligotyping
of the direct repeat locus as secondary typing procedures for M. tuberculosis
isolates having fewer than six copies of IS6110. A total of 88 isolates (100% of
the isolates with fewer than six copies of IS6110 isolated in Arkansas during
1996 and 1997) were included in this study. Among the 88 isolates, 34 different
IS6110 patterns were observed, 10 of which were shared by more than 1 isolate,
involving a total of 64 isolates. The 64 isolates were subdivided into 13
clusters (containing 37 isolates) and 27 unique isolates based on a combination
of IS6110 and pTBN12 fingerprinting and into 11 clusters (containing 51 isolates)
and 13 unique isolates based on a combination of IS6110 fingerprinting and
spoligotyping. Identical spoligotypes were found among isolates having different
IS6110 patterns, as well as among isolates showing different pTBN12 patterns. In
contrast, all isolates that had different IS6110 patterns were found to be unique
by pTBN12 typing. The clustering rate was 73, 58, and 42%, respectively, for
IS6110 fingerprinting alone, IS6110 fingerprinting and spoligotyping combined,
and IS6110 and pTBN12 combined fingerprinting. The data indicate that the pTBN12
method has greater discriminating power among low-copy-number isolates than does
spoligotyping.
PMID- 11015367
TI - Genotyping of hepatitis C virus isolates using CLIP sequencing.
AB - Determination of hepatitis C virus (HCV) genotypes and subtypes has become
increasingly important for the clinical management and prognosis of HCV
infections. The aim of the present study was to assess the specificity and
reliability of a newly developed, commercially available HCV genotyping kit
(TRUGENE HCV 5'NC genotyping kit). This technique utilizes PCR fragments
previously generated by the diagnostic Roche AMPLICOR HCV test, which are
subsequently subjected to simultaneous PCR amplification and direct sequencing
(CLIP sequencing) of the 5' noncoding region (5'NCR). HCV isolates from 100
randomly chosen patients were genotyped by both the TRUGENE HCV 5'NC genotyping
kit and DNA enzyme immunoassay (DEIA). Typing results obtained by both methods
were in complete concordance in 91% of the cases. HCV RNA from the samples with
discordant genotype assignment in both assays was additionally amplified with
primers from the HCV core and NS5B regions. Phylogenetic analysis of the obtained
sequences supported the results obtained from DEIA in six cases and CLIP
sequencing in two cases. In the former six cases, the TRUGENE HCV 5'NC genotyping
kit could not correctly differentiate between subtypes of genotypes 1 and 2 due
to the high conservation of the 5'NCR. However, since there was not any
misclassification between HCV genotypes 1 and non-1 types, the results obtained
with this system are, in general, reliable and can be used in clinical practice.
The TRUGENE HCV 5'NC genotyping kit in our hands proved to be a fast and
convenient technique that might be an attractive option for HCV genotyping in
laboratories already using the Roche AMPLICOR HCV test for diagnostic reverse
transcription-PCR.
PMID- 11015368
TI - Detection of trichomonosis in vaginal and urine specimens from women by culture
and PCR.
AB - Vaginal trichomonosis is a highly prevalent infection which has been associated
with human immunodeficiency virus acquisition and preterm birth. Culture is the
current "gold standard" for diagnosis. As urine-based testing using DNA
amplification techniques becomes more widely used for other sexually transmitted
diseases (STDs) such as gonorrhea and chlamydia, a similar technique for
trichomonosis would be highly desirable. Women attending an STD clinic for a new
complaint were screened for Trichomonas vaginalis by wet-preparation (wet-prep)
microscopy and culture and for the presence of T. vaginalis DNA by specific PCR
of vaginal and urine specimens. The presence of trichomonosis was defined as the
detection of T. vaginalis by direct microscopy and/or culture from either vaginal
samples or urine. The overall prevalence of trichomonosis in the population was
28% (53 of 190). The sensitivity and specificity of PCR using vaginal samples
were 89 and 97%, respectively. Seventy-four percent (38 of 51) of women who had a
vaginal wet prep or vaginal culture positive for trichomonads had microscopic
and/or culture evidence of the organisms in the urine. Two women were positive
for trichomonads by wet prep or culture only in the urine. The sensitivity and
specificity of PCR using urine specimens were 64 and 100%, respectively. These
results indicate that the exclusive use of urine-based detection of T. vaginalis
is not appropriate in women. PCR-based detection of T. vaginalis using vaginal
specimens may provide an alternative to culture.
PMID- 11015369
TI - Rapid differentiation of fermentative from nonfermentative gram-negative bacilli
in positive blood cultures by an impedance method.
AB - Rapid differentiation of fermentative gram-negative bacilli (fermenters) from
nonfermentative gram-negative bacilli (nonfermenters) in positive blood cultures
may help physicians to narrow the choice of appropriate antibiotics for empiric
treatment. An impedance method for direct differentiation of fermenters from
nonfermenters was investigated. The bacterial suspensions (or positive culture
broths containing gram-negative bacteria) were inoculated into the module wells
of a Bactometer (bioMerieux, Inc., Hazelwood, Mo.) containing 1 ml of Muller
Hinton broth. The inoculated modules were incubated at 35 degrees C, and the
change in impedance in each well was continuously monitored. The amount of time
required to cause a series of significant deviations from baseline impedance
values was defined as the detection time (DT). The percent change of impedance
was defined as the change of impedance at the time interval from DT to DT plus 1
h. After testing 857 strains of pure cultures (586 strains of fermenters and 271
strains of nonfermenters), a breakpoint (2.98%) of impedance change was obtained
by discriminant analysis. Strains displaying impedance changes of greater than
2.98% were classified as fermenters; the others were classified as nonfermenters.
By using this breakpoint, 98.6% (340 of 345) of positive blood cultures
containing fermenters and 98% (98 of 100) of positive blood cultures containing
nonfermenters were correctly classified. The impedance method was simple, and the
results were normally available within 2 to 4 h after direct inoculation of
positive blood culture broths.
PMID- 11015370
TI - Elevated phenotypic switching and drug resistance of Candida albicans from human
immunodeficiency virus-positive individuals prior to first thrush episode.
AB - Strains of Candida albicans obtained from human immunodeficiency virus (HIV)
positive individuals prior to their first episode of oral thrush were already in
a high-frequency mode of switching and were far more resistant to a number of
antifungal drugs than commensal isolates from healthy individuals. Switching in
these isolates also had profound effects both on susceptibility to antifungal
drugs and on the levels of secreted proteinase activity. These results suggest
that commensal strains colonizing HIV-positive individuals either undergo
phenotypic alterations or are replaced prior to the first episode of oral thrush.
They also support the suggestion that high-frequency phenotypic switching
functions as a higher-order virulence trait, spontaneously generating in
colonizing populations variants with alterations in a variety of specific
virulence traits.
PMID- 11015371
TI - Increased sensitivity of the BACTEC 460 mycobacterial radiometric broth culture
system does not decrease the number of respiratory specimens required for a
definitive diagnosis of pulmonary tuberculosis.
AB - The BACTEC 460 radiometric mycobacterial broth culture system has consistently
demonstrated faster and increased recovery of Mycobacterium tuberculosis from
respiratory specimens of patients with pulmonary tuberculosis than conventional
culture methods. We thus questioned whether three sputa were still necessary to
definitively diagnose pulmonary tuberculosis if the BACTEC radiometric culture
system were in use. We performed a retrospective analysis of 430 sequential
respiratory specimens submitted from 143 patients and from which M. tuberculosis
had been recovered by in vitro culture and simultaneously assessed the diagnostic
yield of acid-fast smear in this same cohort. M. tuberculosis was recovered from
the first specimen for 117 (82%) of the 143 patients, from the second for 14
patients (10%; cumulative rate, 92%), and from the third for 12 patients (8%;
cumulative rate, 100%). With the exception of those for bronchial brushings,
recovery rates of M. tuberculosis were comparable for all respiratory specimen
types (expectorated sputum, induced sputum, tracheal aspirates, bronchoalveolar
lavage fluids). Only 46 (32%) of these 143 patients had acid-fast bacilli
detected in smears; acid-fast bacilli were detected in the first submitted
specimen for 44 patients (96%) and in the second for the remaining 2 patients
(4%; cumulative rate, 100%). Culture- or smear-positive rates for sequential
specimens obtained from AIDS patients were comparable to those for non-AIDS
patients. Overall, the diagnostic culture yield of sequentially submitted
specimens was not different from previously published studies in which the BACTEC
radiometric culture system had not been used. Despite the documented enhanced
ability of the BACTEC 460 radiometric mycobacterial culture system to recover M.
tuberculosis more often and faster than conventional methods, three sequential
respiratory specimens (regardless of type) were still necessary to definitively
diagnose pulmonary tuberculosis.
PMID- 11015372
TI - Use of a repetitive DNA probe to type clinical and environmental isolates of
Aspergillus flavus from a cluster of cutaneous infections in a neonatal intensive
care unit.
AB - Aspergillus flavus is second to A. fumigatus as a cause of invasive
aspergillosis, but no standard method exists for molecular typing of strains from
human sources. A repetitive DNA sequence cloned from A. flavus and subcloned into
a pUC19 vector, pAF28, was used to type 18 isolates from diverse clinical,
environmental, and geographic sources. The restriction fragment length
polymorphisms generated with EcoRI- or PstI-digested genomic DNA and probed with
digoxigenin-labeled pAF28 revealed complete concordance between patterns.
Eighteen distinct fingerprints were observed. The probe was used to investigate
two cases of cutaneous A. flavus infection in low-birth-weight infants in a
neonatal intensive care unit (NICU). Both infants were transported by the same
ambulance and crew to the NICU on the same day. A. flavus strains of the same
genotype were isolated from both infants, from a roll of tape used to fasten
their umbilical catheters, from a canvas bag used to store the tape in the
ambulance, and from the tape tray in the ambulance isolette. These cases
highlight the need to consider exposures in critically ill neonates that might
occur during their transport to the NICU and for stringent infection control
practices. The hybridization profiles of strains from a second cluster of
invasive A. flavus infections in two pediatric hematology-oncology patients
revealed a genotype common to strains from a definite case patient and a health
care worker. A probable case patient was infected with a strain with a genotype
different from that of the strain from the definite case patient but highly
related to that of an environmental isolate. The high degree of discrimination
and reproducibility obtained with the pAF28 probe underscores its utility for
typing clinical and environmental isolates of A. flavus.
PMID- 11015373
TI - Comparative immunoglobulin G antibody profiles between mother and child (CGMC
test) for early diagnosis of congenital toxoplasmosis.
AB - Early diagnosis of congenital toxoplasmosis is rendered difficult when specific
immunoglobulin M (IgM) and/or IgA antibodies are absent in the blood of the
newborn infant. Since maternal IgG antibodies can cross the placenta,
determination of IgG antibodies in newborn infants has hitherto not been used
routinely for the diagnosis of congenital infection. The aim of this study was to
assess the diagnostic usefulness of an immunoblot assay which compares the early
IgG profiles between the mother and her child (comparative IgG profile between
mother and child; CGMC test) directed against a total cell lysate of Toxoplasma
gondii tachyzoites. Serum samples from 97 newborn infants at risk of toxoplasma
infection were obtained from umbilical cord blood at birth or postnatally until 3
months of life and were directly compared with serum samples from the respective
mothers. Congenital toxoplasmosis was diagnosed only when IgG-reactive protein
bands that were present in any newborn serum samples were absent in the
corresponding maternal serum sample. Congenital infection was defined by
conventional serological assays when IgM and/or IgA antibodies were present in
newborn infant blood or when IgG titers rose within the first 12 months or were
persistently stable for more than 8 months. Using these criteria, congenital
infection was definitely confirmed in 11 cases. Three additional cases were
diagnosed based on indicative data. The CGMC test, which was performed without
knowledge of the results of conventional serologal assays, had sensitivity and
specificity of 82.4 and 93.0%, respectively, and positive and negative predictive
values of 73.7 and 95.7%, respectively. When true positives and true negatives
were considered, the comparative IgG profile had a ratio of 90.9% true results.
The CGMC test thus is useful as an additional assay for the rapid diagnosis of
congenital toxoplasmosis when paired serum samples from mother and child are
available.
PMID- 11015374
TI - 16S ribosomal DNA sequence analysis of a large collection of environmental and
clinical unidentifiable bacterial isolates.
AB - Some bacteria are difficult to identify with phenotypic identification schemes
commonly used outside reference laboratories. 16S ribosomal DNA (rDNA)-based
identification of bacteria potentially offers a useful alternative when
phenotypic characterization methods fail. However, as yet, the usefulness of 16S
rDNA sequence analysis in the identification of conventionally unidentifiable
isolates has not been evaluated with a large collection of isolates. In this
study, we evaluated the utility of 16S rDNA sequencing as a means to identify a
collection of 177 such isolates obtained from environmental, veterinary, and
clinical sources. For 159 isolates (89.8%) there was at least one sequence in
GenBank that yielded a similarity score of > or =97%, and for 139 isolates
(78.5%) there was at least one sequence in GenBank that yielded a similarity
score of > or =99%. These similarity score values were used to defined
identification at the genus and species levels, respectively. For isolates
identified to the species level, conventional identification failed to produce
accurate results because of inappropriate biochemical profile determination in 76
isolates (58.7%), Gram staining in 16 isolates (11.6%), oxidase and catalase
activity determination in 5 isolates (3.6%) and growth requirement determination
in 2 isolates (1.5%). Eighteen isolates (10.2%) remained unidentifiable by 16S
rDNA sequence analysis but were probably prototype isolates of new species. These
isolates originated mainly from environmental sources (P = 0.07). The 16S rDNA
approach failed to identify Enterobacter and Pantoea isolates to the species
level (P = 0.04; odds ratio = 0.32 [95% confidence interval, 0.10 to 1.14]).
Elsewhere, the usefulness of 16S rDNA sequencing was compromised by the presence
of 16S rDNA sequences with >1% undetermined positions in the databases. Unlike
phenotypic identification, which can be modified by the variability of expression
of characters, 16S rDNA sequencing provides unambiguous data even for rare
isolates, which are reproducible in and between laboratories. The increase in
accurate new 16S rDNA sequences and the development of alternative genes for
molecular identification of certain taxa should further improve the usefulness of
molecular identification of bacteria.
PMID- 11015375
TI - Comparison of Danish isolates of Salmonella enterica serovar enteritidis PT9a and
PT11 from hedgehogs (Erinaceus europaeus) and humans by plasmid profiling and
pulsed-field gel electrophoresis.
AB - During the years 1994 to 1998, 10 strains of Salmonella enterica serovar
Enteritidis phage type 11 (PT11) and 6 PT9a strains were isolated from Danish
hedgehogs, together with 7 strains that did not yield phage susceptibility
patterns conforming with any known phage type (routine dilution no conformity
[RDNC]). From 1995 to 1998, five Danish patients were reported infected with
serovar Enteritidis PT11 and two with PT9a. All serovar Enteritidis PT11, PT9a,
and RDNC isolates from hedgehogs and humans were analyzed by pulsed-field gel
electrophoresis (PFGE), plasmid profiling, and restriction fragment length
polymorphism (RFLP) of plasmids. By use of S1 nuclease and HindIII, the PT11 and
PT9a isolates had identical plasmid profiles and RFLP patterns, which differed
from the RDNC profiles. The PFGE profiles were identical for all serovar
Enteritidis PT11 and PT9a strains from hedgehogs, four of five human strains of
serovar Enteritidis PT11, and two human strains of serovar Enteritidis PT9a,
irrespective of restriction enzyme, whereas the last human strain deviated
slightly when NotI was used but not when XbaI or SpeI was used. The results
indicate that serovar Enteritidis PT9a and PT11 are closely related and that PT11
and PT9a from Danish hedgehogs and humans belong to the same clonal lineage.
PMID- 11015377
TI - Helicobacter pylori: clonal population structure and restricted transmission
within families revealed by molecular typing.
AB - Helicobacter pylori infects up to 50% of the human population worldwide. The
infection occurs predominantly in childhood and persists for decades or a
lifetime. H. pylori is believed to be transmitted from person to person. However,
tremendous genetic diversity has been reported for these bacteria. In order to
gain insight into the epidemiological basis of this phenomenon, we performed
molecular typing of H. pylori isolates from different families. Fifty-nine H.
pylori isolates from 27 members of nine families were characterized by using
restriction fragment length polymorphism analysis of five PCR-amplified genes, by
pulsed-field gel electrophoresis (PFGE) of chromosomal DNA, and by vacA and cagA
genotyping. The 16S rRNA gene exhibited little allelic variation, as expected for
a unique bacterial species. In contrast, the vacA, flaA, ureAB, and lspA-glmM
genes were highly polymorphic, with a mean genetic diversity of 0.83, which
exceeds the levels recorded for all other bacterial species. In conjunction with
PFGE, 59 H. pylori isolates could be differentiated into 21 clonal types. Each
individual harbored only one clone, occasionally with a clonal variant. Identical
strains were always found either between siblings or between a mother and her
children. Statistical analysis revealed clonality of population structure in all
isolates. The results of this study suggest the possible coexistence of a large
array of clonal lineages that are evolving in each individual in isolation from
one another. Transmission appears to occur primarily from mother to child and
perhaps between siblings.
PMID- 11015376
TI - Molecular surveillance of European quinolone-resistant clinical isolates of
Pseudomonas aeruginosa and Acinetobacter spp. using automated ribotyping.
AB - Nosocomial isolates of Pseudomonas aeruginosa and Acinetobacter spp. exhibit high
rates of resistance to antibiotics and are often multidrug resistant. In a
previous study (D. Milatovic, A. Fluit, S. Brisse, J. Verhoef, and F. J. Schmitz,
Antimicrob. Agents Chemother. 44:1102-1107, 2000), isolates of these species that
were resistant to sitafloxacin, a new advanced-generation fluoroquinolone with a
high potency and a broad spectrum of antimicrobial activity, were found in high
proportion in 23 European hospitals. Here, we investigate the clonal diversity of
the 155 P. aeruginosa and 145 Acinetobacter spp. sitafloxacin-resistant isolates
from that study by automated ribotyping. Numerous ribogroups (sets of isolates
with indistinguishable ribotypes) were found among isolates of P. aeruginosa (n =
34) and Acinetobacter spp. (n = 16), but the majority of the isolates belonged to
a limited number of major ribogroups. Sitafloxacin-resistant isolates (MICs > 2
mg/liter, used as a provisional breakpoint) showed increased concomitant
resistance to piperacillin, piperacillin-tazobactam, ceftriaxone, ceftazidime,
amikacin, gentamicin, and imipenem. The major ribogroups were repeatedly found in
isolates from several European hospitals; these isolates showed higher levels of
resistance to gentamicin and imipenem, and some of them appeared to correspond to
previously described multidrug-resistant international clones of P. aeruginosa
(serotype O:12) and Acinetobacter baumannii (clones I and II). Automated
ribotyping, when used in combination with more discriminatory typing methods, may
be a convenient library typing system for monitoring future epidemiological
dynamics of geographically widespread multidrug-resistant bacterial clones.
PMID- 11015378
TI - Evaluation of D-xylose and 1% methyl-alpha-D-glucopyranoside fermentation tests
for distinguishing Enterococcus gallinarum from Enterococcus faecium.
AB - To determine the validity of the rapid xylose and methyl-alpha-D-glucopyranoside
(MDG) fermentation tests in distinguishing Enterococcus gallinarum from
Enterococcus faecium, 156 well-characterized clinical isolates of enterococci (55
E. gallinarum, 91 E. faecium, and 10 Enterococcus faecalis isolates) known to be
of different clones were examined in a blinded fashion. Species identification
was confirmed by PCR of the ddl ligase genes of E. faecium and E. faecalis and
the vanC1 gene of E. gallinarum. Xylose tests were performed with D-xylose
tablets by using a heavy bacterial suspension and were interpreted after 2 h of
incubation. Standard MDG fermentation tests were read after 24 h of incubation.
The xylose fermentation test had a sensitivity of 98% (54 of 55) and a
specificity of 99% (100 of 101) in distinguishing E. gallinarum from E. faecium
and E. faecalis. The standard MDG test had a sensitivity of 100% (55 of 55) and a
specificity of 95% (96 of 101) after 24 h. The xylose fermentation test is a
simple method, easily incorporated into laboratory protocols, that distinguishes
E. gallinarum from E. faecium with high sensitivity and specificity in 2 h. The
standard MDG test has high sensitivity and can be useful in ruling out the
presence of E. gallinarum but requires overnight incubation.
PMID- 11015379
TI - Genotypic determination of Mycobacterium tuberculosis antibiotic resistance using
a novel mutation detection method, the branch migration inhibition M.
tuberculosis antibiotic resistance test.
AB - A novel method for the detection of any alteration within a defined sequence has
recently been demonstrated (A. Lishanski, N. Kurn, and E. F. Ullman, Nucleic
Acids Res. 28:E42, 2000; A. Lishanski, Clin. Chem. 46:9, 2000). Essential to this
method are the generation of partial duplexes that are capable of forming four
stranded structures and the ability to detect inhibition of branch migration in
these structures (I. G. Panyutin and P. Hsieh, J. Mol. Biol. 230:413-424, 1993).
Inhibition of branch migration indicates the presence of sequence alteration.
This mutation detection method, termed branch migration inhibition (BMI), is
suitable for the detection of drug resistance in M. tuberculosis, which is
frequently associated with multiple mutations within known genes. We describe the
genotypic determination of the rifampin (RMP) and pyrazinamide (PZA)
susceptibilities of M. tuberculosis isolates, using BMI coupled with the
luminescence oxygen channeling immunoassay (LOCI) (E. F. Ullman et al., Proc.
Natl. Acad. Sci. USA 91:5426-5430, 1994). RMP and PZA resistances are associated
with multiple mutations within the rpoB and pncA genes, respectively. M.
tuberculosis genomic DNA samples prepared from 46 clinical isolates were used for
genotypic determination of RMP resistance in a "blind study." Similarly, PZA
resistance was determined using genomic DNA samples prepared from 37 clinical
isolates. Full agreement of the genotypic and phenotypic determinations of drug
susceptibility was demonstrated. RMP susceptibility determination directly from
cells of 10 clinical isolates grown in culture was also demonstrated. The
genotypic result of only 1 out of 10 isolates did not agree with the phenotypic
susceptibility testing result. Sequence analysis of the rpoB gene of this
clinical isolate revealed a single base substitution, most likely a silent point
mutation. The new BMI-LOCI mutation detection method is a rapid and accurate
procedure for the genotypic determination of the RMP and PZA susceptibilities of
M. tuberculosis clinical isolates. BMI can also be detected by using commercially
available automated enzyme-linked immunosorbent assay plate formats (Lishanski et
al., Nucleic Acids Res. 28:E42, 2000).
PMID- 11015380
TI - Pneumococcal pspA sequence types of prevalent multiresistant pneumococcal strains
in the United States and of internationally disseminated clones.
AB - In a recent genotypic survey of beta-lactam-resistant pneumococci recovered in
different areas of United States during 1997, eight clonal types that each
represented 3 to 40 isolates accounted for 134 of 144 isolates (G. Gherardi, C.
Whitney, R. Facklam, and B. Beall, J. Infect. Dis. 181:216-229, 2000). We
determined the degree of pspA gene diversity among these 134 isolates and for 11
previously characterized internationally disseminated multiresistant strains.
Thirty-four different pspA restriction profiles were determined for an amplicon
encompassing the variable portion of the structural gene that encodes the surface
exposed domain of PspA and a variable-length proline-rich putative cell wall
associated domain. These restriction profiles closely correlated with those of 33
different pspA sequence types of an approximately 230-residue region
corresponding to residues 182 to 410 of the strain Rx1 PspA. These residues
encompass a 100-residue clade-defining region known to contain cross-protective
epitopes for which 17 sequence types were found. Distinct, conserved pspA
sequence types were found for the majority of strains within seven of the eight
U.S. clonal types assessed, while one pulsed-field gel electrophoresis type was
represented by isolates of three distinct PspA clades. Sequence typing of pspA
provides an added level of specificity in the subtyping of isolates and is a
necessary first step in determining the components needed in a PspA vaccine which
could elicit effective cross-protective coverage.
PMID- 11015382
TI - Evaluation of amplified fragment length polymorphism analysis for inter- and
intraspecific differentiation of Mycobacterium bovis, M. tuberculosis, and M.
ulcerans.
AB - The usefulness of amplified fragment length polymorphism (AFLP) analysis was
evaluated for the discrimination of Mycobacterium bovis (17 strains), M.
tuberculosis (15 strains), and M. ulcerans (12 strains) at the inter- and
intraspecific level. The AFLP technique is a whole-genome coverage genotypic
fingerprinting method based on the selective PCR amplification of modified
restriction fragments obtained through a double enzymatic digest and subsequent
ligation of double-stranded restriction site-specific adapter oligonucleotides.
Selective amplification of ApaI/TaqI templates with primer combination A02-T02
(both having an additional C at their 3' end) generated autoradiographic AFLP
fingerprints that were grouped by numerical analysis in two main AFLP clusters
allowing clear separation of M. ulcerans (cluster I) from the M. tuberculosis
complex members M. bovis and M. tuberculosis (cluster II). Calculation of
similarities using the band-based Dice correlation coefficient instead of the
Pearson product-moment correlation coefficient revealed a further subgrouping in
cluster II. The two resulting subclusters corresponded with the phenotypic
identity of M. bovis and M. tuberculosis, respectively, and could also be
visually identified by two AFLP marker bands. Because of the relatively low
degree of genotypic variation among the AFLP band patterns of the latter two
taxa, no correlation could be found with previously reported molecular typing
data or with geographical origin. The use of primer combination A02-T01 (the
latter having an A as selective base) did not increase the resolving power within
the M. tuberculosis complex but resulted in a visual subgrouping of the M.
ulcerans strains that was not observed with primer combination A02-T02. Based on
the presence or absence of a single AFLP marker band, the M. ulcerans isolates
could be unambiguously classified in two continental types corresponding with the
African and Australian origin of the strains, respectively. In conclusion, the
radioactive AFLP method proved to be a reproducible and reliable taxonomic tool
for the differentiation of the three mycobacterial species under study and also
demonstrated its potential use for typing of M. ulcerans strains when employing
multiple primer combinations.
PMID- 11015381
TI - Detection of borreliacidal antibodies in dogs after challenge with Borrelia
burgdorferi-infected ixodes scapularis ticks.
AB - Detection of borreliacidal antibodies is an accurate serodiagnostic test for
confirmation of Lyme disease in humans. In this study, 13 pathogen-free beagles,
12 to 26 weeks old, were infected with Borrelia burgdorferi by tick challenge.
Dogs were monitored for clinical signs and symptoms of Lyme disease along with
borreliacidal antibody production against B. burgdorferi sensu stricto isolates
297 and 50772. Ten (77%) dogs developed lameness in one or more legs within 210
days after attachment of Ixodes scapularis ticks. Eight (80%) of the lame animals
had concurrent fever of > or =38 degrees C. Spirochetes were also recovered from
the skin and joints of 12 (92%) dogs, but rarely from other organs. Borreliacidal
antibodies against B. burgdorferi isolate 297 were detected in only four (31%)
dogs, and the levels of killing antibodies remained low for the duration of the
infection. In contrast, borreliacidal antibodies against B. burgdorferi isolate
50772 were detected in 13 (100%) dogs within 21 days of infection. Furthermore,
the borreliacidal antibody levels correlated with the severity of B. burgdorferi
infection. Detection of borreliacidal antibodies, especially against B.
burgdorferi isolate 50772, is also a reliable serodiagnostic test for detection
of Lyme disease in dogs.
PMID- 11015383
TI - Genotyping of rotaviruses in environmental water and stool samples in Southern
Switzerland by nucleotide sequence analysis of 189 base pairs at the 5' end of
the VP7 gene.
AB - Stool specimens from children (<4 years old) with diarrhea were collected over a
1-year period in Ticino (southern region of Switzerland). During the same period,
environmental samples were collected from surface waters in the proximity of
major water treatment plants. From treatment plants, samples were collected from
the raw sewage and before the release of the treated water. From rivers, samples
were collected before and after receiving the treated waters. A single-step
reverse transcription (RT)-PCR amplification of the entire VP7 gene from
extracted double-stranded RNA was developed. For the water samples, a further
nested PCR was necessary to increase sensitivity. All amplified viral products
were sequenced, and the sequence profile was compared to that of the VP7 genes of
human and animal rotaviruses from GenBank. Rotavirus strains are characterized by
outer capsid proteins G (glycoprotein) and P (protease-cleaved protein). Correct
G genotyping of viral sequences from stool and water samples was possible by
analyzing only 189 bp at the 5' end of the VP7 gene. In the Ticino region, the
most predominant G genotype among clinical and water samples was G1. Genotypes G2
and G4 were found only among clinical samples. We also detected rotavirus G1-type
sequences in feces from a healthy adult. This finding corroborates the hypothesis
that healthy adults act as potential reservoirs for the spread of rotavirus in
the environment. In our experiments, this RT-PCR-based method for rotavirus
genotyping has proven to be a useful tool for epidemiological investigations.
PMID- 11015384
TI - Comparison of phenotypic and genotypic methods for pyrazinamide susceptibility
testing with Mycobacterium tuberculosis.
AB - Mycobacterium tuberculosis converts pyrazinamide to its active form by using the
enzyme pyrazinamidase. This enzyme is coded for on the pncA gene, and mutations
in the pncA gene result in absence of active enzyme, conferring resistance to the
drug pyrazinamide. We investigated 27 strains of Mycobacterium tuberculosis
suspected of being multidrug resistant. Each isolate was tested for
susceptibility to pyrazinamide by the BACTEC 460TB method, and 19 were
pyrazinamide resistant. The presence of active pyrazinamidase enzyme was sought
by using the Wayne assay, which was positive in all of the sensitive isolates and
four of the resistant isolates. The pncA gene was amplified by PCR, and mutations
were sought by single-strand conformation polymorphism (SSCP) analysis. We
identified four isolates which were phenotypically resistant to pyrazinamide, but
which had active pyrazinamide enzyme on the Wayne assay and normal pncA gene
SSCP. MICs measured by BACTEC 460TB and susceptibility testing at a lower pH of
5.5 confirmed genuine resistance. The pncA gene was sequenced in these four
isolates and found not to have any mutations. This implies that an alternative
mechanism of resistance exists in these strains. We conclude that genotypic
assessment of pyrazinamide resistance is unreliable, because it depends on the
identification of a single resistance mechanism. Phenotypic methods such as the
BACTEC 460TB technique remain the best methods for pyrazinamide susceptibility
testing.
PMID- 11015385
TI - Rapid quantification and differentiation of human polyomavirus DNA in undiluted
urine from patients after bone marrow transplantation.
AB - A combined PCR assay was developed for the detection and typing of human
polyomavirus (huPoV) in clinical samples, consisting of (i) a qualitative
seminested PCR assay (snPCR) to discriminate between huPoV BK and JC and (ii) a
high-throughput, quantitative TaqMan PCR assay (TM-PCR) for the general detection
of huPoV. The TM-PCR detects huPoV DNA in a linear range from 10(7) to 10(1)
copies per assay. In reproducibility runs, the inter- and intra-assay
variabilities were < or =60 and < or =50%, respectively. The snPCR assay uses a
set of four primers for the same region of the BK and JC viral genomes. In the
first round of amplification, two general primers were used; in the second round,
one of these general primers and two additional, BK- or JC-specific primers were
used simultaneously to produce amplicons of different sizes specific for BK virus
(246 bp) and JC virus (199 bp), respectively. We tested different urine dilutions
in order to determine the inhibitory effects of urine on PCR amplification.
Furthermore, we compared the use of native urine with DNA purified by different
preparation procedures. Our results show, that a 1:10 dilution of the urine led
to complete reduction of the amplification inhibition found with 6% of undiluted
urine samples. In a clinical study including 600 urine specimens, our assay
turned out to be fast, cheap, and reliable in both qualitative and quantitative
aspects.
PMID- 11015386
TI - Differentiation between Candida dubliniensis and Candida albicans by fatty acid
methyl ester analysis using gas-liquid chromatography.
AB - Candida dubliniensis is often found in mixed culture with C. albicans, but its
recognition is hampered as the color of its colonies in primary culture on
CHROMagar Candida varies. Furthermore, definite identification of C. dubliniensis
is difficult to achieve, time-consuming, and expensive. Therefore, a method to
discriminate between these two closely related yeast species by fatty acid methyl
ester (FAME) analysis using gas-liquid chromatography (Sherlock Microbial
Identification System [MIS]; MIDI, Inc., Newark, Del.) was developed. Although
the chromatograms of these two species revealed no obvious differences when
applying FAME analysis, a new library (CADLIB) was successfully created using
Sherlock Library Generation Software (MIDI). The amount and frequency of FAME was
analyzed using library training files (n = 10 for each species), preferentially
those comprising reference strains. For testing the performance of the CADLIB,
clinical isolates genetically assigned to the respective species (C. albicans, n
= 32; C. dubliniensis, n = 28) were chromatographically analyzed. For each
isolate tested, MIS computed a similarity index (SI) indicating a hierarchy of
possible strain fits. When using the newly created library CADLIB, the SIs for C.
albicans and C. dubliniensis ranged from 0.11 to 0.96 and 0.53 to 0. 93 (for all
but one), respectively. Only three isolates of C. albicans (9.4%) were
misidentified as C. dubliniensis, whereas all isolates of C. dubliniensis were
correctly identified. Resulting differentiation accuracy was 90.6% for C.
albicans and 100% for C. dubliniensis. Cluster analysis and principal component
analysis of the resulting FAME profiles showed two clearly distinguishable
clusters matching up with two assigned species for the strains tested. Thus, the
created library proved to be well suited to discriminate between these two
species.
PMID- 11015387
TI - Expression of a gene encoding the major antigenic protein 2 homolog of ehrlichia
chaffeensis and potential application for serodiagnosis.
AB - The major antigenic protein 2 (MAP2) homolog of Ehrlichia chaffeensis was cloned
and expressed. The recombinant protein was characterized and tested in an enzyme
linked immunosorbent assay (ELISA) format for potential application in the
serodiagnosis of human monocytic ehrlichiosis. The recombinant protein, which
contained a C-terminal polyhistidine tag, had a molecular mass of approximately
26 kDa. The antigen was clearly identified by Western immunoblotting using
antihistidine antibody. However, immune sera failed to react with the recombinant
on immunoblots when the antigen was denatured by heat or reduced using beta
mercaptoethanol. The recombinant MAP2 (rMAP2) was used in an ELISA format with 60
blinded serum samples. Twenty of the serum samples were previously demonstrated
to contain antibodies reactive with E. chaffeensis by indirect immunofluorescence
assays (IFAs). The remaining 40 samples were seronegative. All samples negative
by IFA were also found to be negative for antibodies against the rMAP2 of E.
chaffeensis by using the ELISA. Only 1 of 20 IFA-positive samples tested negative
in the rMAP2 ELISA. There was 100% agreement using IFA-negative samples and 95%
agreement using IFA-positive samples, resulting in a 97.5% overall agreement
between the two assays. These data suggest that the rMAP2 homolog of E.
chaffeensis may have potential as a test antigen for the serodiagnosis of human
monocytic ehrlichiosis. To our knowledge, this recombinant is unique because it
is thus far the only E. chaffeensis recombinant antigen that has been shown to
work in an ELISA format.
PMID- 11015388
TI - Two enzyme immunoassays and PCR for detection of Helicobacter pylori in stool
specimens from pediatric patients before and after eradication therapy.
AB - This study of pediatric patients was intended to determine the suitability of
stool PCR and two antigen enzyme immunoassays (EIAs; Premier Platinum HpSA and
the novel FemtoLab H. pylori), which detect Helicobacter pylori antigens in
feces, as pretreatment diagnostic tools and especially as posttreatment control.
Forty-nine H. pylori-infected children with dyspepsia received eradication
therapy. Successful treatment was determined by a negative [(13)C]urea breath
test 4 and 12 weeks after discontinuation of therapy. Fecal specimens were
collected prior to eradication therapy as well as 4 weeks after the end of
treatment. Successfully treated children delivered stool samples at 6, 8, and 12
weeks posttreatment also. Specimens were examined by seminested PCR and Premier
Platinum HpSA and were reexamined by both EIAs as soon as FemtoLab H. pylori was
available. In the first test series, the overall sensitivities of PCR and Premier
Platinum HpSA were 93.0 and 91.1%, respectively. With specimens collected at 4
weeks after treatment, the respective specificities were 68.8 and 79.3%. After
longer follow-up periods, however, they gradually increased to 100 and 96.9%,
respectively. In the new test series, Premier Platinum HpSA delivered a
considerably lower number of false-positive results (4 versus 18), indicating
intertest variations. The overall test sensitivity was 94.6%, and the overall
specificity was 97.5%. FemtoLab H. pylori showed an excellent performance with an
overall sensitivity and specificity of 98.2 and 98.1%, respectively. Thus, in
contrast to PCR, both EIAs were shown to be suitable for early posttreatment
control.
PMID- 11015389
TI - Evaluation of the Etest method for determining voriconazole susceptibilities of
312 clinical isolates of Candida species by using three different agar media.
AB - Performance of the Etest for voriconazole susceptibility testing of 312 isolates
of Candida spp. was assessed against that of the National Committee for Clinical
Laboratory Standards (NCCLS) microdilution broth method. The NCCLS method
employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at
35 degrees C. Etest MICs were determined with RPMI agar containing 2% glucose
(RPG), Casitone agar (CAS), and antibiotic medium 3 (AM3) agar and were read
after incubation for 48 h at 35 degrees C. The Candida spp. isolates included C.
albicans (n = 174), C. glabrata (n = 55), C. tropicalis (n = 31), C. parapsilosis
(n = 39), C. krusei (n = 5), C. lusitaniae (n = 2), and C. guilliermondii (n =
6). The Etest results obtained using RPG correlated well with the reference MICs.
Overall agreement ranged from 91% for C. glabrata to 100% for C. tropicalis, C.
parapsilosis, C. guilliermondii, C. krusei, and C. lusitaniae. When CAS was used,
agreement ranged from 80% for C. krusei to 100% for C. parapsilosis, C.
guilliermondii, and C. lusitaniae. With AM3, agreement ranged from 58% for C.
glabrata to 100% for C. lusitaniae and C. guilliermondii. The Etest method using
RPG appears to be a useful method for determining voriconazole susceptibilities
of Candida species.
PMID- 11015390
TI - Immunodiagnosis of Echinococcus infections: confirmatory testing and species
differentiation by a new commercial Western Blot.
AB - The Echinococcus Western Blot IgG (LDBIO Diagnostics, Lyon, France), using a
whole larval antigen from Echinococcus multilocularis, was evaluated for
serodiagnosis and differentiation between two human parasitic infections of
worldwide importance: cystic echinococcosis, due to Echinococcus granulosus, and
alveolar echinococcosis, due to E. multilocularis. Fifty and 61 serum samples
from patients with cystic and alveolar echinococcosis, respectively, were used
for assessing diagnostic sensitivity. The sensitivity of the assay was compared
with those of screening tests used for these applications. Sera used for
assessing cross-reactivities were from 154 patients with other diseases, either
parasitic or not. The assay allowed the detection of serum immunoglobulin G
antibodies in 97% of Echinococcus-infected patients. It had a higher sensitivity
than screening assays for the detection for each echinococcosis. The assay
allowed us to correctly distinguish between E. granulosus- and E. multilocularis
infected patients in 76% of cases. It did not allow us to distinguish active from
inactive forms of both echinococcoses. The occurrence of cross-reactivities with
neurocysticercosis indicates the necessity for retesting sera with species
specific antigens, for rare patients with neurologic disorders. This study shows
the usefulness of the commercially available Echinococcus Western Blot IgG for
the serological confirmation of human echinococcosis.
PMID- 11015391
TI - Helicobacter aurati sp. nov., a urease-positive Helicobacter species cultured
from gastrointestinal tissues of Syrian hamsters.
AB - A novel helicobacter with the proposed name Helicobacter aurati (type strain MIT
97-5075c) has been isolated from the inflamed stomachs and ceca of adult Syrian
hamsters. The new species is fusiform with multiple bipolar sheathed flagella and
periplasmic fibers; it contains urease and gamma-glutamyl transpeptidase. By 16S
rRNA sequencing and repetitive element PCR-based DNA fingerprinting, it was found
that H. aurati represents a distinct taxon and clusters with Helicobacter
muridarum, Helicobacter hepaticus, and Helicobacter sp. MIT 94-022. H. aurati was
recovered from hamsters housed in various research and vendor facilities. Further
studies are necessary to define its association with disease and other microbiota
in hamsters, as well as its impact on research projects involving hamsters. H.
aurati (GenBank accession number AF297868) can be used in animal experiments to
define the factors that are important for gastric helicobacter pathogenesis.
PMID- 11015392
TI - Molecular and antigenic characterization of a highly evolved derivative of the
type 2 oral poliovaccine strain isolated from sewage in Israel.
AB - An unusual, highly diverged derivative of the Sabin type 2 oral poliovaccine
(OPV) strain was recovered from environmental samples during routine screening
for wild polioviruses. Virus was cultivated in L20B cells and then passaged on
BGM cells at 40 degrees C (RCT [reproductive capacity at supraoptimal
temperature]-positive marker) to select against most OPV strains. All but 1 of 25
RCT-positive OPV-derived environmental isolates were antigenically and
genetically (>99.5% VP1 sequence match) similar to the respective Sabin strains.
However, isolate PV2/4568-1/ISR98 (referred to below as 4568-1) escaped
neutralization with Sabin 2-specific monoclonal antibodies and cross-adsorbed
sera, and had multiple nucleotide substitutions (220 of 2,646; 8.3%) in the P1
capsid region. Fourteen of the 44 associated amino acid substitutions in the
capsid mapped to neutralizing antigenic sites. Neutralizing titers in the sera of
50 Israeli children 15 years old were significantly lower to 4568-1 (geometric
mean titer [GMT], 47) than to Sabin 2 (GMT, 162) or to the prototype wild strain,
PV2/MEF-1/EGY42 (GMT, 108). Two key attenuating sites had also reverted in 4568-1
(A(481) to G in the 5' untranslated region and the VP1 amino acid I(143) to T),
and the isolate was highly neurovirulent for transgenic mice expressing the
poliovirus receptor (PVR-Tg21 mice). The extensive genetic divergence of 4568-1
from the parental Sabin 2 strain suggested that the virus had replicated in one
or more people for approximately 6 years. The presence in the environment of a
highly evolved, neurovirulent OPV-derived poliovirus in the absence of polio
cases has important implications for strategies for the cessation of immunization
with OPV following global polio eradication.
PMID- 11015393
TI - Development of a PCR-based line probe assay for identification of fungal
pathogens.
AB - We report on a reverse-hybridization line probe assay (LiPA) which when combined
with PCR amplification detects and identifies clinically significant fungal
pathogens including Candida, Aspergillus, and Cryptococcus species. DNA probes
have been designed from the internal transcribed-spacer (ITS) regions of Candida
albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis, Candida
krusei, Candida dubliniensis, Cryptococcus neoformans, Aspergillus fumigatus,
Aspergillus versicolor, Aspergillus nidulans and Aspergillus flavus. The probes
were incorporated into a LiPA for detection of biotinylated ITS PCR products, and
the specificity of the probes was evaluated. We established LiPA detection limits
for ITS 1 and for full ITS amplicons for genomic DNA from C. albicans, A.
fumigatus, and C. neoformans. Further evaluation of the LiPA was carried out on
clinical fungal isolates. One hundred twenty-seven isolates consisting of
dimorphic yeasts and dermatophytic and filamentous fungi were tested by the LiPA,
which correctly identified 77 dimorphic yeasts and 23 of the filamentous
isolates; the remaining 27 isolates represented species of fungi for which probes
were not included in the LiPA. The fungal-PCR-LiPA technology was applied to
blood samples inoculated with Candida cells which were pretreated by minibead
beating to mechanically disrupt the cells, with the DNA extracted by either a
previously described guanidium thiocyanate-silica method or the commercially
available QIAmp tissue kit. PCR amplification of the extracted DNA and subsequent
DNA probe hybridization in the LiPA assay yielded detection limits of 2 to 10
cells/ml. An internal standard control was included in the PCR amplification to
monitor for PCR inhibition. This fungal PCR-LiPA assay is robust and sensitive
and can easily be integrated into a clinical-testing laboratory with the
potential for same-day diagnosis of fungal infection.
PMID- 11015394
TI - Comparison of the CMV brite turbo assay and the digene hybrid capture CMV DNA
(Version 2.0) assay for quantitation of cytomegalovirus in renal transplant
recipients.
AB - We compared the CMV Brite Turbo Kit (BT) and the Digene Hybrid Capture CMV DNA
(version 2.0) assay (HC2) in the quantitation of pp65 antigenemia and
cytomegalovirus (CMV) DNA levels in immunosuppressed renal transplant recipients.
Of 123 blood specimens collected from 24 renal transplant recipients, BT and HC2
assays detected 35 and 39 positive samples, respectively. The overall concordance
rate between the two assays was 90%. Discordant results were observed at low
levels of viremia, so that 8 samples were HC2 positive but BT negative and
another 4 were BT positive but HC2 negative. There was good correlation (R(2) =
0.766; P<0.01) between the levels of CMV DNA and pp65 antigenemia in the 31
concordant positive samples. Correlation between results obtained with the two
assays was confirmed by longitudinal studies for a patient who developed clinical
CMV disease. HC2 may be more sensitive at low viremia levels and allow earlier
detection of impending CMV disease. The BT assay offered the advantage of a rapid
(2-h) turnaround time. We conclude that BT and HC2 assays have similar
sensitivity and efficacy in the diagnosis and monitoring of CMV infection and
disease in renal transplant recipients. While the HC2 assay would be appropriate
for centers that handle a large number of samples, the BT test may be more
suitable for small sample numbers or when results are needed urgently.
PMID- 11015395
TI - Characterization of Staphylococcus aureus coagulase type VII isolates from
staphylococcal food poisoning outbreaks (1980-1995) in Tokyo, Japan, by pulsed
field gel electrophoresis.
AB - Staphylococcus aureus coagulase type VII strains have been the strains most
frequently isolated from staphylococcal food poisoning outbreaks in Tokyo, Japan.
We applied pulsed-field gel electrophoresis (PFGE) of chromosomal DNA digested
with SmaI to characterize 129 coagulase type VII strains. These were isolated
from 129 cases occurring in outbreaks in 35 districts during a 16-year period
(1980-1995). The 129 outbreak strains were classified into three types,
designated A (n = 115), B (n = 10), and C (n = 4). Types A and C were further
divided into 33 (A1 to A33) and 4 (C1 to C4) subtypes, respectively. Strains of
the same subtypes were isolated from food poisoning cases in the same districts
at time intervals of 1 or 2 to 5 years. PFGE typing appears to be a useful method
for subdividing strains of S. aureus coagulase type VII. A combination of
coagulase typing and PFGE typing would provide more detailed information than the
former method alone in epidemiologic investigations of staphylococcal food
poisoning.
PMID- 11015396
TI - Utilization of exocellular mannan from Rhodotorula glutinis as an immunoreactive
antigen in diagnosis of leptospirosis.
AB - Previously, Rhodotorula glutinis was reported to produce a large amount of
exocellular mannan, having a repeating unit of -->3)-D-Manp-(1-->4)-D-Manp-(1-->.
Recently, we found that antigenic polysaccharides of Leptospira biflexa serovar
patoc strain Patoc I have the same repeating unit and cross-react with antisera
raised against extended strains of other leptospires (K. Matsuo, E. Isogai, and
Y. Araki, Carbohydr. Res., in press). This structural identity and the difficulty
of producing and isolating antigens led us to confirm the usefulness of
Rhodotorula mannan as an immunoreactive antigen in a serological diagnosis of
leptospirosis. In the present investigation, we confirmed the structural identity
of an exocellular mannan isolated from R. glutinis AHU 3479 and tried to use it
as an immunoreactive antigen in a serological diagnosis of leptospirosis. From
its chemical analysis and (1)H- and (13)C-labeled nuclear magnetic resonance
spectrometry, the Rhodotorula mannan was confirmed to consist of the same
disaccharide units. Furthermore, such a preparation was shown to immunoreact to
various sera from patients suffering with leptospirosis as well as to most rabbit
antiserum preparations obtained from immunization with various strains of
pathogenic leptospires. Therefore, the Rhodotorula mannan preparation is useful
as an immunoreactive antigen in the serological diagnosis for leptospirosis.
PMID- 11015397
TI - Evaluation of a PCR primer based on the isocitrate dehydrogenase gene for
detection of Helicobacter pylori in feces.
AB - In order to improve detection and identification of Helicobacter pylori in highly
contaminated samples, we evaluated new specific primers based on the DNA base
sequence within the isocitrate dehydrogenase (icd) gene to amplify a 1,200-bp DNA
segment. The specificity of the icd primer was tested against DNA derived from
various bacteria, including 7 Helicobacter species and a panel of 1 gram
variable, 2 gram-positive, and 16 gram-negative bacteria, as well as DNA from
houseflies and feces from H. pylori-negative patients. The primers permitted the
detection of all clinical H. pylori isolates tested, but no reactions were
observed with negative controls. Several procedures for DNA extraction from feces
were evaluated using PCR with icd primers. The lower limits of detection of H.
pylori DNA from two different sources containing the same number of H. pylori
organisms, a pure culture and feces spiked with H. pylori, were established for
each extraction method tested. The results were 8.0 x 10(3) CFU/ml for cultures
of pure H. pylori, and 8.0 x 10(6) CFU/ml for H. pylori from feces, using the
phenol-chloroform method; 8.0 x 10(2) and 7.0 x 10(3) CFU/ml, respectively, for a
glass matrix and chaotropic solution protocol; 8.0 x 10(2) and 7.0 x 10(3)
CFU/ml, respectively, for the QIAamp tissue kit; and 5.0 x 10(2) and 5.0 x 10(3)
CFU/ml, respectively, for the XTRAX DNA extraction kit. We conclude that the use
of the icd gene as a primer for PCR represents a specific and sensitive assay for
detection of H. pylori in highly contaminated samples.
PMID- 11015398
TI - Prevalence of O1/K1- and O2/K3-reactive Actinobacillus suis in healthy and
diseased swine.
AB - A cell surface antigen-typing system was devised for the swine pathogen
Actinobacillus suis and used to examine the prevalence of different
lipopolysaccharide (O) types in healthy and diseased pigs. The strains examined
in this study were isolated from a variety of locations in Canada and from
Kansas. Lipopolysaccharide preparations of 151 isolates of A. suis were
characterized by immunoblotting using polyclonal antisera generated to strains
SO4 (O1/K1), H89-1173 (O2/K3), and VSB 3714, a rough strain. Approximately 54%
(62 of 114) of A. suis isolates from diseased pigs, all (11 of 11) isolates from
healthy pigs, and all (4 of 4) reference strains reacted with O1/K1 antiserum.
More than 80% (18 of 22) of A. suis strains used for bacterin production and
approximately 41% (47 of 114) of isolates from diseased pigs bound O2/K3
antiserum. One isolate appeared to be rough, and five were untypeable. O1/K1- and
O2/K3-reactive strains were equally prevalent in Kansas, whereas O2/K3-reactive
strains were more common in Quebec and western Canada and O1/K1 strains were most
common in Ontario. The fact that virtually all of the strains submitted for
bacterin production were O2/K3-reactive strains is consistent with the notion
that these strains may be more virulent than O1/K1 strains; alternatively, this
may reflect geographic or other biases. In addition, we observed cross-reactivity
between A. suis cell surface antigens and swine antisera to several other
important pathogens. This finding may explain why previous attempts to develop a
simple serodiagnostic test for A. suis have been unsuccessful.
PMID- 11015400
TI - Diagnosis of cutaneous leishmaniasis in Colombia: the sampling site within
lesions influences the sensitivity of parasitologic diagnosis.
AB - Parasitologic confirmation of cutaneous leishmaniasis is obligatory before
chemotherapy can be considered. Direct microscopic examination of scrapings taken
from indurated borders of ulcers has been routinely used as primary method of
diagnosis. In this report we compared the sensitivity of examination of dermal
scrapings taken from the bottoms of ulcers (BDS) with that of dermal scrapings
taken from indurated active margins of lesions (MDS) in a total of 115 patients.
The sensitivities of the microscopic examination were 90.4 and 78.3% for BDS and
MDS samples, respectively. When the PCR method was used with a group of 40
patients, we also observed a higher sensitivity when BDS samples were examined
(80.8% in BDS samples versus 57.7% in MDS samples). The improvement of the
diagnostic sensitivity in the BDS samples appears to be related to the higher
parasite load and more easily detectable morphology of amastigotes in the centers
of the ulcers. Other parasitologic diagnostic methods, such as culture and
histopathologic examination of biopsies, are less sensitive (67.5 and 64.3%,
respectively). Aspirate culture, however, was shown to be the most sensitive
method for the diagnosis of patients with chronic ulcers. When microscopic
examinations of both MDS and BDS samples are combined, the sensitivity of
diagnosis may rise up to 94%. We therefore recommend this method as a primary
routine procedure for diagnosis of cutaneous leishmaniasis.
PMID- 11015399
TI - PCR assessment of Chlamydia trachomatis infection of semen specimens processed
for artificial insemination.
AB - In order to ascertain the microbiological quality of stored semen specimens
processed for artificial insemination by a donor (AID), we developed a PCR assay
targeting the chlamydial plasmid to detect Chlamydia trachomatis in semen. The
lower limit of detection of this assay corresponded to 2.5 to 5 elementary bodies
per microl of semen. A total of 669 cryopreserved ejaculates from 97 asymptomatic
donors were tested for C. trachomatis infection. Twelve ejaculates, originating
from four donors, were found to be positive, indicating a 4% prevalence of C.
trachomatis infection among the donor population studied. Cross-contamination
between the cryopreserved specimens in the storage container was studied by
typing using sequence analysis of PCR-amplified omp1 genes of the strains. Two
donors were infected with serovar E, one was infected with serovar F, and one was
infected with serovar K. For two donors, the duration of C. trachomatis
positivity could be assessed. One donor donated C. trachomatis-positive semen for
at least 4 successive months, and the other did so for at least 16 months. The
occurrence of C. trachomatis infection in cryopreserved donor semen indicates
that ejaculates from donors not tested for a C. trachomatis infection just prior
to donation should be tested for infection by a direct test such as the PCR
described here. Direct testing of semen specimens will detect not only donors
with an active infection but also C. trachomatis-infected ejaculates already
stored and will thus improve the microbiological quality of AID, since
discrepancies in the presence of C. trachomatis in urine and semen specimens have
been reported.
PMID- 11015402
TI - Bacillus anthracis diversity in Kruger National Park.
AB - The Kruger National Park (KNP), South Africa, has a recorded history of periodic
anthrax epidemics causing widespread disease among wild animals. Bacillus
anthracis is the causative agent of anthrax, a disease primarily affecting
ungulate herbivores. Worldwide there is little diversity among B. anthracis
isolates, but examination of variable-number tandem repeat (VNTR) loci has
identified six major clones, with the most dissimilar types split into the A and
B branches. Both the A and B types are found in southern Africa, giving this
region the greatest genetic diversity of B. anthracis worldwide. Consequently,
southern Africa has been hypothesized to be the geographic origin of B.
anthracis. In this study, we identify the genotypic types of 98 KNP B. anthracis
isolates using multiple-locus VNTR analysis. Two major types are evident, the A
branch and the B branch. The spatial and temporal distribution of the different
genotypes indicates that anthrax epidemic foci are independent, though correlated
through environmental cues. Kruger B isolates were found on significantly higher
calcium and higher-pH soils than were Kruger type A. This relationship between
genotype and soil chemistry may be due to adaptive differences among divergent
anthrax strains. While this association may be simply fortuitous, adaptation of A
types to diverse environmental conditions is consistent with their greater
geographic dispersal and genetic dissimilarity.
PMID- 11015403
TI - Prevalence of enterotoxin genes in Aeromonas spp. isolated from children with
diarrhea, healthy controls, and the environment.
AB - Aeromonads are causative agents of a number of human infections. Even though
aeromonads have been isolated from patients suffering from diarrhea, their
etiological role in gastroenteritis is unclear. In spite of a number of virulence
factors produced by Aeromonas species, their association with diarrhea has not
been clearly linked. Recently, we have characterized a heat-labile cytotonic
enterotoxin (Alt), a heat-stable cytotonic enterotoxin (Ast), and a cytotoxic
enterotoxin (Act) from a diarrheal isolate of Aeromonas hydrophila. Alt and Ast
are novel enterotoxins which are not related to cholera toxin; Act is aerolysin
related and has hemolytic, cytotoxic, and enterotoxic activities. We studied the
distribution of the alt, ast, and act enterotoxin genes in 115 of 125 aeromonads
isolated from 1, 735 children with diarrhea, in all 27 aeromonads isolated from
830 control children (P = 7 x 10(-4) for comparison of rates of isolation of
aeromonads from cases versus those from controls), and in 120 randomly selected
aeromonads from different components of surface water in Bangladesh. Aeromonas
isolates which were positive only for the presence of the alt gene had similar
distributions in the three sources; the number of isolates positive only for the
presence of the ast gene was significantly higher for the environmental samples
than for samples from diarrheal children; and isolates positive only for the
presence of the act gene were not found in any of the three sources. Importantly,
the number of isolates positive for both the alt and ast genes was significantly
higher for diarrheal children than for control children and the environment.
Thus, this is the first study to indicate that the products of both the alt and
ast genes may synergistically act to induce severe diarrhea. In 26 patients,
Aeromonas spp. were isolated as the sole enteropathogen. Analysis of clinical
data from 11 of these patients suggested that isolates positive for both the alt
and ast genes were associated with watery diarrhea but that isolates positive
only for the alt gene were associated with loose stools. Most of the isolates
from the three sources could be classified into seven phenospecies and eight
hybridization groups. For the first time, Aeromonas eucrenophila was isolated
from two children, one with diarrhea and another without diarrhea.
PMID- 11015404
TI - Phenotypic and genetic characterization of Lactococcus garvieae isolated in Spain
from lactococcosis outbreaks and comparison with isolates of other countries and
sources.
AB - The phenotypic and genetic analysis results for 84 isolates of Lactococcus
garvieae (including 62 strains from trout with lactococcosis from four different
countries, 7 strains from cows and water buffalos with subclinical mastitis, 3
from water, and 10 from human clinical samples) are presented. There was great
phenotypic heterogeneity (13 different biotypes) based on the acidification of
saccharose, tagatose, mannitol, and cyclodextrin and the presence of the enzymes
pyroglutamic acid arylamidase and N-acetyl-beta-glucosaminidase. L. garvieae also
exhibited high genetic diversity by pulsed-field gel electrophoresis (PFGE), with
19 different pulsotypes among the isolates of L. garvieae studied. Only
epidemiologically related strains, like the Spanish and Italian fish isolates and
the cow and water buffalo isolates, displayed a close genetic relationship by
PFGE, while the strains isolated from sporadic clinical cases, like the human
isolates, were genetically unrelated. Overall, a general correlation between
phenotypic and genetic data was observed. Epidemiological analysis of biotype and
PFGE results indicated that the trout lactococcosis outbreaks in Spain and
Portugal and those in France and Italy were produced by genetically unrelated
clones. In Spain, two different clones were detected; the outbreaks diagnosed
from 1995 onward were produced by a clone (biotype 2, pulsotype A1) which,
although genetically related, was different from the one that was responsible for
the outbreaks studied between 1991 and 1994 (biotype 1, pulsotype B). The
Portuguese isolate had a biochemical profile identical to that of the Spanish
strain isolated from 1995 onward and is also genetically closely related to this
strain (pulsotype A2). There was a close relationship between the two pulsotypes
(E and F) found in the Italian isolates. The French isolate (biotype 3, pulsotype
D) was not genetically related to any other L. garvieae fish isolate. These
results suggest the existence of diverse infection sources for the different
lactococcosis outbreaks.
PMID- 11015401
TI - Class 1 integron-borne, multiple-antibiotic resistance encoded by a 150-kilobase
conjugative plasmid in epidemic vibrio cholerae O1 strains isolated in Guinea
Bissau.
AB - In the 1996-1997 cholera epidemic in Guinea-Bissau, surveillance for
antimicrobial resistance showed the emergence of a multidrug-resistant strain of
Vibrio cholerae O1 during the course of the epidemic. The strain was resistant to
ampicillin, erythromycin, tetracycline, furazolidone, aminoglycosides,
trimethoprim, and sulfamethoxazole. Concomitant with the emergence of this
strain, we observed a resurgence in the number of registered cholera cases as
well as an increase in the case fatality rate from 1.0% before the emergence of
the multiple-drug-resistant strain to 5.3% after the emergence of the strain. Our
study shows that the strain contained a 150-kb conjugative multiple-antibiotic
resistance plasmid with class 1 integron-borne gene cassettes encoding resistance
to trimethoprim (dhfrXII) and aminoglycosides [ant(3")-1a]). The finding of
transferable resistance to almost all of the antibiotics commonly used to treat
cholera is of great public health concern. Studies should be carried out to
determine to what extent the strain or its resistance genes have been spread to
other areas where cholera is endemic.
PMID- 11015405
TI - Rapid and sensitive plate method for detection of Aspergillus fumigatus.
AB - The routine identification of Aspergillus fumigatus in clinical samples involves,
apart from direct examination, the isolation of the organism on a plate followed
by its microscopic characterization. This approach lacks sensitivity,
specificity, and speed. A new procedure has been developed combining microcolony
formation on a nylon membrane filter at 45 degrees C with the detection of a
specific 4-methylumbelliferyl-alpha-L-arabinopyranoside cleaving enzyme activity
in digitonin permeabilized cells. The test takes approximately 14 h and has an
efficiency of 98.2% and false-positive and -negative rates of 0 and 3.1%,
respectively. When applied to 188 clinical samples taken from patients with
proven or nonproven presence of Aspergillus species, a good agreement with the
conventional plate-microscopy method was obtained.
PMID- 11015406
TI - Evaluation of phenotypic and genotypic methods for subtyping Campylobacter jejuni
isolates from humans, poultry, and cattle.
AB - Six methods for subtyping of Campylobacter jejuni were compared and evaluated
with a collection of 90 isolates from poultry, cattle, and sporadic human
clinical cases as well as from a waterborne outbreak. The applied methods were
Penner heat-stable serotyping; automated ribotyping (RiboPrinting); random
amplified polymorphic DNA typing (RAPD); pulsed-field gel electrophoresis (PFGE);
restriction fragment length polymorphisms of the flagellin gene, flaA (fla-RFLP);
and denaturing gradient gel electrophoresis of flaA (fla-DGGE). The methods were
evaluated and compared on the basis of their abilities to identify isolates from
one outbreak and discriminate between unrelated isolates and the agreement
between methods in identifying clonal lines. All methods identified the outbreak
strain. For a collection of 80 supposedly unrelated isolates, RAPD and PFGE were
the most discriminatory methods, followed by fla-RFLP and RiboPrinting. fla-DGGE
and serotyping were the least discriminative. All isolates included in this study
were found to be typeable by each of the methods. Thirteen groups of potentially
related isolates could be identified using a criterion that at least four of the
methods agreed on clustering of isolates. None of the subtypes could be related
to only one source; rather, these groups represented isolates from different
sources. Furthermore, in two cases isolates from cattle and human patients were
found to be identical according to all six methods.
PMID- 11015407
TI - Discrimination between viable and dead Encephalitozoon cuniculi (Microsporidian)
spores by dual staining with sytox green and calcofluor white M2R.
AB - Microsporidia are obligate intracellular parasites, recognized as causing chronic
diarrhea and systemic disease in AIDS patients, organ transplant recipients,
travelers, and malnourished children. Species of microsporidia that infect humans
have been detected in drinking-water sources, and methods are needed to ascertain
if these microsporidia are viable and capable of causing infections. In this
study, Calcofluor White M2R and Sytox Green stains were used in combination to
differentiate between live (freshly harvested) and dead (boiled) Encephalitozoon
cuniculi spores. Calcofluor White M2R binds to chitin in the microsporidian spore
wall. Dual-stained live spores appeared as turquoise-blue ovals, while dead
spores appeared as white-yellow ovals at an excitation wavelength of 395 to 415
nm used for viewing the Calcofluor stain. Sytox Green, a nuclear stain, is
excluded by live spores but penetrates compromised spore membranes. Dual-stained
dead spores fluoresced bright yellow-green when viewed at an excitation
wavelength of 470 to 490 nm, whereas live spores failed to stain with Sytox
Green. After live and dead spores were mixed at various ratios, the number of
viably stained spores detected in the dual-staining procedure correlated (P =
0.0025) with the expected numbers of viable spores. Spore mixtures were also
assayed for infectivity in a focus-forming assay, and a correlation (P = 0.0002)
was measured between the percentage of focus-forming microsporidia and the
percentage of expected infectious spores in each mixture. By analysis of
variance, no statistically significant differences were measured between the
percentage of viably stained microsporidia and the percentage of infectious
microsporidia (P = 0.964) in each mixture. These results suggest that Calcofluor
White M2R and Sytox Green stains, when used together, may facilitate studies to
identify viable microsporidia.
PMID- 11015408
TI - Molecular epidemiology of Entamoeba spp.: evidence of a bottleneck (Demographic
sweep) and transcontinental spread of diploid parasites.
AB - Entamoeba histolytica causes amebic colitis and liver abscess in developing
countries such as Mexico and India. Entamoeba dispar is morphologically identical
but is not associated with disease. Here we determined the ploidy of E.
histolytica and developed PCR-based methods for distinguishing field isolates of
E. histolytica or E. dispar. Fluorescence in situ hybridization showed that E.
histolytica trophozoites are diploid for five "single-copy" probes tested.
Intergenic sequences between superoxide dismutase and actin 3 genes of clinical
isolates of E. histolytica from the New and Old Worlds were identical, as were
those of E. dispar. These results suggest a bottleneck or demographic sweep in
entamoebae which infect humans. In contrast, E. histolytica and E. dispar genes
encoding repeat antigens on the surface of trophozoites (Ser-rich protein) or
encysting parasites (chitinase) were highly polymorphic. chitinase alleles
suggested that the early axenized strains of E. histolytica, HM-1 from Mexico
City, Mexico, and NIH-200 from Calcutta, India, are still present and that
similar E. dispar parasites can be identified in both the New and Old Worlds. Ser
rich protein alleles, which suggested the presence of the HM-1 strain in Mexico
City, included some E. histolytica genes that predicted Ser-rich proteins with
very few repeats. These results, which suggest diversifying selection at
chitinase and Ser-rich protein loci, demonstrate the usefulness of these alleles
for distinguishing clinical isolates of E. histolytica and E. dispar.
PMID- 11015409
TI - Detection and quantitation of human immunodeficiency virus type 1 in the female
genital tract. The Division of AIDS Treatment Research Initiative 009 Study
Group.
AB - Human immunodeficiency virus type 1 (HIV-1) was detected in the genital tracts of
59% of 225 women by RNA PCR and in 7% of the women by culture. In a comparison of
two sampling methods, endocervical swabs were more sensitive than cervicovaginal
lavage for HIV-1 RNA detection by PCR but not by culture and their sensitivity
was independent of the concentration of HIV-1 RNA.
PMID- 11015410
TI - InTray GC medium versus modified Thayer-Martin agar plates for diagnosis of
gonorrhea from endocervical specimens.
AB - A new self-contained medium system for the cultivation of Neisseria gonorrhoeae
was compared to modified Thayer-Martin medium for the diagnosis of gonorrhea from
endocervical specimens. There was no difference in the ability of the two methods
to support the growth of N. gonorrhoeae.
PMID- 11015412
TI - Comparison between plasma and whole blood specimens for detection of Aspergillus
DNA by PCR.
AB - Ninety-six plasma and whole blood specimens from nine selected patients were
analyzed for the presence of Aspergillus DNA. Nineteen specimens from three
patients with proven aspergillosis were PCR positive in both materials, whereas
an additional 22 were PCR positive in whole blood only. All 36 samples from six
patients without signs of aspergillosis were negative in both assays. We conclude
that although plasma and whole blood spiked with Aspergillus conidia showed an
identical lower detection limit (10 CFU), the sensitivity of plasma PCR was lower
than that of PCR performed on whole blood samples.
PMID- 11015411
TI - Performance of five agar media for recovery of fungi from isolator blood
cultures.
AB - We studied the recovery of 1,270 fungal isolates from 176,144 Isolator blood
cultures (0.72% positive) on bacterial and fungal media, under routine and
differing incubation conditions. Except with Histoplasma capsulatum, chocolate
agar incubated for only 3 days proved to be an excellent medium for the recovery
of fungi from the Isolator system.
PMID- 11015413
TI - Evaluation of Etest for susceptibility testing of Mycobacterium tuberculosis.
AB - The Etest method for susceptibility testing of Mycobacterium tuberculosis was
compared to the agar proportion method using four first-line agents and two
fluoroquinolones. Catergorical agreement between the methods was 100% for
rifampin, ethambutol, streptomycin, and ofloxacin and 98% for isoniazid. Results
were obtained in 6 to 10 days by Etest. The Etest method is suitable for testing
the agents evaluated against M. tuberculosis.
PMID- 11015414
TI - Distribution of a specific 500-base-pair fragment in mycobacterium bovis isolates
from Sardinian cattle.
AB - Amplification of a specific, 500-bp fragment from Mycobacterium bovis isolates
and use of the fragment to differentiate between Mycobacterium tuberculosis and
M. bovis was previously reported (J. G. Rodriguez, G. A. Meja, P. Del Portillo,
M. E. Patarroyo, and L. A. Murillo, Microbiology 141:2131-2138, 1995). In the
present study, 30 M. bovis isolates from Sardinian cattle were examined for the
presence of this 500-bp fragment; 4 of the 30 isolates lacked the fragment. This
result indicates that identification of M. bovis strains by amplification of the
500-bp sequence may lead to false-negative results.
PMID- 11015415
TI - Utility of tissue culture for detection of Toxoplasma gondii in vitreous humor of
patients diagnosed with toxoplasmic retinochoroiditis.
AB - Laboratory recovery and confirmation of the etiologic agent in necrotizing
retinochoroiditis are problematic. Tissue culture and intraocular antibody titers
were compared as adjuncts to clinical diagnosis for toxoplasmic
retinochoroiditis: the correlations were 91 and 67%, respectively. Isolation of
Toxoplasma gondii may establish a definitive diagnosis in patients with
toxoplasmic retinochoroiditis.
PMID- 11015416
TI - Use of amplified fragment length polymorphisms for typing Corynebacterium
diphtheriae.
AB - Amplified fragment length polymorphism (AFLP) was investigated for the
differentiation of Corynebacterium diphtheriae isolates. Analysis using Taxotron
revealed 10 distinct AFLP profiles among 57 isolates. Strains with ribotype
patterns D1, D4, and D12 could not be distinguished; however, the technique
discriminated isolates of ribotype patterns D3, D6, and D7 further. AFLP was
rapid, fairly inexpensive, and reproducible and could be used as an alternative
to ribotyping.
PMID- 11015418
TI - G protein variation in respiratory syncytial virus group A does not correlate
with clinical severity.
AB - Respiratory syncytial virus group A strain variations of 28 isolates from The
Netherlands collected during three consecutive seasons were studied by analyzing
G protein sequences. Several lineages circulated repeatedly and simultaneously
during the respective seasons. No relationships were found between lineages on
the one hand and clinical severity or age on the other.
PMID- 11015417
TI - A probable new Helicobacter species isolated from a patient with bacteremia.
AB - A probable new Helicobacter species was isolated from the blood of a 14-month-old
aboriginal child who presented with vomiting, diarrhea, fever, and dry cough. The
most similar 16S rRNA gene sequence was that of Helicobacter fennelliae CCUG
18820(T) but the new sequence differed from it by at least 32 base substitutions
and by the presence of a large (353-nucleotide) intervening sequence.
PMID- 11015419
TI - Evaluation of the Alexon-trend ProSpecT Campylobacter microplate assay.
AB - We evaluated stool specimens known to contain or be free of Campylobacter by
traditional culture, using the ProSpecT Campylobacter microplate assay (Alexon
Trend, Ramsey, Minn.). This rapid enzyme immunoassay for the detection of
Campylobacter-specific antigens demonstrated 96% sensitivity and 99% specificity
and is an acceptable alternative method of Campylobacter detection.
PMID- 11015420
TI - Absence of serotype-specific surface antigen and altered teichoic acid
glycosylation among epidemic-associated strains of Listeria monocytogenes.
AB - Outbreaks of food-borne listeriosis have often involved strains of serotype 4b.
Examination of multiple isolates from three different outbreaks revealed that ca.
11 to 29% of each epidemic population consisted of strains which were negative
with the serotype-specific monoclonal antibody c74.22, lacked galactose from the
teichoic acid of the cell wall, and were resistant to the serotype 4b-specific
phage 2671.
PMID- 11015421
TI - Comparison of six commercial DNA extraction kits for recovery of cytomegalovirus
DNA from spiked human specimens.
AB - We evaluated six commercially available DNA extraction kits for their ability to
recover DNA from various dilutions of cytomegalovirus (CMV) added to four
different specimens: bronchoalveolar lavage, cerebral spinal fluid, plasma, and
whole blood. The kits evaluated included the Puregene DNA isolation kit (PG),
Generation Capture Column kit, MasterPure DNA purification kit, IsoQuick nucleic
acid extraction kit, QIAamp blood kit, and NucliSens isolation kit (NS). All six
kits evaluated effectively removed PCR inhibitors from each of the four specimen
types and produced consistently positive results down to a spiked concentration
of 200 PFU of whole CMV per ml. However, the NS and PG resulted in the most
consistently positive results at the lowest concentrations of spiked CMV (4 and
0.4 PFU/ml) and, in this evaluation, offered the most sensitive methods for
extracting CMV DNA from the four different spiked specimens. Processing time and
cost were also evaluated.
PMID- 11015422
TI - Clinical comparison of nonvented aerobic BacT/Alert blood culture bottle and
standard aerobic bottle for detection of microorganisms in blood.
AB - The current BacT/Alert standard aerobic (VA) blood culture bottle was redesigned
and designated a nonvented aerobic (NVA) culture bottle; this bottle does not
require venting. A total of 3,873 sets of blood samples for culture were obtained
from adult patients with suspected bacteremia or fungemia. The NVA bottle showed
performance equivalent to that of the VA bottle for recovery and speed of
detection of microorganisms from blood without the need for venting the bottle.
PMID- 11015423
TI - Molecular analysis of methicillin-resistant Staphylococcus aureus as a causative
agent of bronchopulmonary infection: relation to colonization in the upper
respiratory tract.
AB - Using five diagnostic markers, we compared the types of 72 strains of methicillin
resistant Staphylococcus aureus (MRSA) isolated simultaneously from the nasal
cavity, pharynx, and sputum from 24 patients. Almost identical MRSA types had
colonized the nasal cavity and sputum from the same patient for 21 (88%) of the
patients. We speculate that most MRSA organisms isolated in sputum are derived
from the nasal cavity, while a few are derived from the pharynx.
PMID- 11015424
TI - Isolation of Moraxella canis from an ulcerated metastatic lymph node.
AB - Moraxella canis was isolated in large numbers from an ulcerated supraclavicular
lymph node of a terminal patient, who died a few days later. Although the patient
presented with septic symptoms and with a heavy growth of gram-negative
diplococci in the lymph node, blood cultures remained negative. M. canis is an
upper-airway commensal from dogs and cats and is considered nonpathogenic for
humans, although this is the third reported human isolate of this species.
PMID- 11015425
TI - Evaluation of different preservation and storage methods for Malassezia spp.
AB - Freezing at -80 degrees C, lyophilization, preservation in distilled water, and
storage in different culture media were performed in order to find a suitable
method that allowed a prolonged storage of Malassezia spp. Freezing at -80
degrees C was the only method successful at maintaining all species.
PMID- 11015427
TI - Vancomycin-intermediate Staphylococcus aureus in Korea.
AB - Recent reports on some methicillin-resistant Staphylococcus aureus (MRSA) with
reduced susceptibility to vancomycin have been a major concern in Korea because
of the widespread use of vancomycin due to a high prevalence of MRSA in the
country. We describe a 45-year-old man with long-standing pelvic abscess due to
MRSA. In spite of vancomycin and teicoplanin treatment for a long period of time,
the patient died from MRSA sepsis. The blood culture isolate of MRSA exhibited
reduced susceptibility to vancomycin (MIC, 8 microg/ml). This is the first report
of a vancomycin-intermediate S. aureus case from Korea.
PMID- 11015426
TI - VP4 and VP7 genotyping by reverse transcription-PCR of human rotavirus in mexican
children with acute diarrhea.
AB - Dual typing (VP4 and VP7) of rotavirus obtained from 257 Mexican children during
three epidemiological seasons was performed by reverse transcription-PCR. The
P1G1 genotype was the most prevalent (40%), followed by P1G3 (19%) and P2G2
(16%). Thirty-one specimens (12%) presented mixed infections, while some
genotypes were not found. This is the first dual typing of isolates from diarrhea
cases in Mexico.
PMID- 11015429
TI - Osteomyelitis caused by Staphylococcus schleiferi and evidence of
misidentification of this Staphylococcus species by an automated bacterial
identification system.
AB - We report a case of sternal osteomyelitis due to Staphylococcus schleiferi in a
patient who underwent thoracic surgery. This constitutes the first documented
case of osteomyelitis caused by this Staphylococcus species. We also relate our
experience in the utilization of commercially available MicroScan panels for the
identification of this microorganism.
PMID- 11015428
TI - Evaluation of the abbott LCx HIV-1 RNA quantitative, a new assay for quantitative
determination of human immunodeficiency virus type 1 RNA.
AB - A new quantitative reverse transcription (RT)-PCR assay for human
immunodeficiency virus type 1 (HIV-1) RNA (Abbott LCx HIV RNA Quantitative assay)
has been compared with the Organon NucliSens assay on 521 retrospective samples
obtained from HIV-1-positive patients monitored during highly active
antiretroviral therapy, 79 of whom were assayed also by the Chiron Quantiplex 3.0
system and on characterized panels. The LCx system showed a moderate correlation
(r = 0.795) and gave higher results than the NucliSens system on 245 of 327
concordant positive samples, with similar sensitivity. Correlation with
Quantiplex system results was higher (r = 0.943). LCx reproducibility was very
good; the procedure was simple, well controlled, and rapid (up to 48 results in 7
h). The HIV RNA quantitative assay on the LCx system is suitable for routine use.
PMID- 11015430
TI - Histoplasmosis of the thyroid.
AB - Fungal infection of the thyroid is rare. Most reported cases have involved
Aspergillus, Coccidioides, and Candida species in the setting of disseminated
disease. Infection of the thyroid with Histoplasma capsulatum is rarely reported
as part of disseminated disease, even in geographic areas where histoplasmosis is
endemic. We report a 52-year-old woman with a previous Hashimoto's disease and
non-Hodgkin's lymphoma in which a diffuse enlarged thyroid gland with a large
nodule was the only apparent locus of histoplasmosis. Fine-needle aspiration of
the thyroid was an important diagnostic tool in establishing the diagnosis of
histoplasmosis of the thyroid. The patient was initially treated with
itraconazole (400 mg/day) for the fungal infection and six cycles of chemotherapy
for the lymphoma. At a 6-month follow-up examination, the patient was doing well
on suppressive therapy of itraconazole (200 mg/day), with no symptoms and with
regression of the thyroid nodule and cervical adenopathy.
PMID- 11015431
TI - Granulomatous amebic encephalitis in a patient with AIDS: isolation of
acanthamoeba sp. Group II from brain tissue and successful treatment with
sulfadiazine and fluconazole.
AB - A patient with AIDS, treated with highly active antiretroviral therapy and
trimethoprim-sulfamethoxazole, presented with confusion, a hemifield defect, and
a mass lesion in the right occipital lobe. A brain biopsy confirmed granulomatous
amebic encephalitis (GAE) due to Acanthamoeba castellanii. The patient was
treated with fluconazole and sulfadiazine, and the lesion was surgically excised.
This is the first case of AIDS-associated GAE responding favorably to therapy.
The existence of a solitary brain lesion, absence of other sites of infection,
and intense cellular response in spite of a very low CD4 count conditioned the
favorable outcome. We review and discuss the diagnostic microbiologic options for
the laboratory diagnosis of infections due to free-living amebae.
PMID- 11015432
TI - Mycobacterium branderi from both a hand infection and a case of pulmonary
disease.
AB - Mycobacterium branderi, a potential human pathogen first characterized in 1995,
has been isolated from respiratory tract specimens. We report here a case in
which M. branderi was the only organism isolated upon culture from a hand
infection. This isolate, along with a second isolate from a bronchial specimen,
was subjected to conventional identification tests for mycobacterial species.
Further analysis by high-performance liquid chromatography (HPLC) of mycolic
acids and 16S rRNA gene sequencing was performed, and the antibiotic
susceptibility profile was determined for both strains. Biochemical tests and the
HPLC pattern were consistent with that of M. branderi and M. celatum, which are
very similar. The 16S rRNA gene sequence of both strains corresponded to that of
M. branderi and enabled us to confidently differentiate this organism from other
closely related species such as M. celatum. This contributes to a further
understanding of the status of this species as a potential human pathogen as well
as illustrating the need for molecular diagnostics as a complementary method for
the identification of rare mycobacterial species.
PMID- 11015433
TI - Failure to detect circulating Aspergillus markers in a patient with chronic
granulomatous disease and invasive aspergillosis.
AB - We report a patient with chronic granulomatous disease who developed invasive
pulmonary aspergillosis and a subphrenic abscess. During treatment, high levels
of Aspergillus antigen were detected in the abscess, but circulating antigen and
Aspergillus DNA were undetectable in the serum.
PMID- 11015434
TI - Natural killer T cell activation inhibits hepatitis B virus replication in vivo.
AB - We have previously reported that hepatitis B virus (HBV)-specific CD8(+)
cytotoxic T lymphocytes and CD4(+) helper T lymphocytes can inhibit HBV
replication in the liver of HBV transgenic mice by secreting interferon (IFN)
gamma when they recognize viral antigen. To determine whether an activated innate
immune system can also inhibit HBV replication, in this study we activated
natural killer T (NKT) cells in the liver of HBV transgenic mice by a single
injection of alpha-galactosylceramide (alpha-GalCer), a glycolipid antigen
presented to Valpha14(+)NK1.1(+) T cells by the nonclassical major
histocompatibility complex class I-like molecule CD1d. Within 24 h of alpha
GalCer injection, IFN-gamma and IFN-alpha/beta were detected in the liver of HBV
transgenic mice and HBV replication was abolished. Both of these events were
temporally associated with the rapid disappearance of NKT cells from the liver,
presumably reflecting activation-induced cell death, and by the recruitment of
activated NK cells into the organ. In addition, prior antibody-mediated depletion
of CD4(+) and CD8(+) T cells from the mice did not diminish the ability of alpha
GalCer to trigger the disappearance of HBV from the liver, indicating that
conventional T cells were not downstream mediators of this effect. Finally, the
antiviral effect of alpha-GalCer was inhibited in mice that are genetically
deficient for either IFN-gamma or the IFN-alpha/beta receptor, indicating that
most of the antiviral activity of alpha-GalCer is mediated by these cytokines.
Based on these results, we conclude that alpha-GalCer inhibits HBV replication by
directly activating NKT cells and by secondarily activating NK cells to secrete
antiviral cytokines in the liver. In view of these findings, we suggest that, if
activated, the innate immune response, like the adaptive immune response, has the
potential to control viral replication during natural HBV infection. In addition,
the data suggest that therapeutic activation of NKT cells may represent a new
strategy for the treatment of chronic HBV infection.
PMID- 11015435
TI - Germinal center initiation, variable gene region hypermutation, and mutant B cell
selection without detectable immune complexes on follicular dendritic cells.
AB - Serum antibody (Ab) can play several roles during B cell immune responses. Among
these is to promote the deposition of immune complexes (ICs) on follicular
dendritic cells (FDCs). ICs on FDCs are generally thought to be critical for
normal germinal center (GC) formation and the development and selection of memory
B cells. However, it has been very difficult to test these ideas. To determine
directly whether FDC-bound complexes do indeed function in these roles, we have
developed a transgenic (Tg) mouse in which all B lymphocytes produce only the
membrane-bound form of immunoglobulin M. Immune Tg mice have 10,000-fold less
specific Ab than wild-type mice and lack detectable ICs on FDCs. Nonetheless,
primary immune responses and the GC reaction in these mice are robust, suggesting
that ICs on FDCs do not play critical roles in immune response initiation and GC
formation. Moreover, as indicated by the presence and pattern of somatic
mutations, memory cell formation and selection appear normal in these IC
deficient GCs.
PMID- 11015436
TI - Control of gammaherpesvirus latency by latent antigen-specific CD8(+) T cells.
AB - The contribution of the latent antigen-specific CD8(+) T cell response to the
control of gammaherpesvirus latency is currently obscure. Some latent antigens
induce potent T cell responses, but little is known about their induction or the
role they play during the establishment of latency. Here we used the murine
gammaherpesvirus system to examine the expression of the latency-associated M2
gene during latency and the induction of the CD8(+) T cell response to this
protein. M2, in contrast to the M3 latency-associated antigen, was expressed at
day 14 after infection but was undetectable during long-term latency. The
induction of the M2(91-99)/K(d) CD8(+) T cell response was B cell dependent,
transient, and apparently induced by the rapid increase in latently infected
cells around day 14 after intranasal infection. These kinetics were consistent
with a role in controlling the initial "burst" of latently infected cells. In
support of this hypothesis, adoptive transfer of an M2-specific CD8(+) T cell
line reduced the initial load of latently infected cells, although not the long
term load. These data represent the first description of a latent antigen
specific immune response in this model, and suggest that vaccination with latent
antigens such as M2 may be capable of modulating latent gammaherpesvirus
infection.
PMID- 11015437
TI - Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral
immune response.
AB - B lymphocyte stimulator (BLyS) is a newly identified monocyte-specific TNF family
cytokine. It has been implicated in the development of autoimmunity, and
functions as a potent costimulator with antiimmunoglobulin M in B cell
proliferation in vitro. Here we demonstrate that BLyS prominently enhances the
humoral responses to both T cell-independent and T cell-dependent antigens,
primarily by attenuation of apoptosis as evidenced by the prolonged survival of
antigen-activated B cells in vivo and in vitro. BLyS acts on primary splenic B
cells autonomously, and directly cooperates with CD40 ligand (CD40L) in B cell
activation in vitro by protecting replicating B cells from apoptosis. Moreover,
although BLyS alone cannot activate the cell cycle, it is sufficient to prolong
the survival of naive resting B cells in vitro. Attenuation of apoptosis by BLyS
correlates with changes in the ratios between Bcl-2 family proteins in favor of
cell survival, predominantly by reducing the proapoptotic Bak and increasing its
prosurvival partners, Bcl-2 and Bcl-xL. In either resting or CD40L-activated B
cells, the NF-kappaB transcription factors RelB and p50 are specifically
activated, suggesting that they may mediate BLyS signals for B cell survival.
Together, these results provide direct evidence for BLyS enhancement of both T
cell-independent and T cell-dependent humoral immune responses, and imply a role
for BLyS in the conservation of the B cell repertoire. The ability of BLyS to
increase B cell survival indiscriminately, at either a resting or activated
state, and to cooperate with CD40L, further suggests that attenuation of
apoptosis underlies BLyS enhancement of polyclonal autoimmunity as well as the
physiologic humoral immune response.
PMID- 11015438
TI - CD1b-mediated T cell recognition of a glycolipid antigen generated from
mycobacterial lipid and host carbohydrate during infection.
AB - T cells recognize microbial glycolipids presented by CD1 proteins, but there is
no information regarding the generation of natural glycolipid antigens within
infected tissues. Therefore, we determined the molecular basis of CD1b-restricted
T cell recognition of mycobacterial glycosylated mycolates, including those
produced during tissue infection in vivo. Transfection of the T cell receptor
(TCR) alpha and beta chains from a glucose monomycolate (GMM)-specific T cell
line reconstituted GMM recognition in TCR-deficient T lymphoblastoma cells. This
TCR-mediated response was highly specific for natural mycobacterial glucose-6-O
(2R, 3R) monomycolate, including the precise structure of the glucose moiety, the
stereochemistry of the mycolate lipid, and the linkage between the carbohydrate
and the lipid. Mycobacterial production of antigenic GMM absolutely required a
nonmycobacterial source of glucose that could be supplied by adding glucose to
media at concentrations found in mammalian tissues or by infecting tissue in
vivo. These results indicate that mycobacteria synthesized antigenic GMM by
coupling mycobacterial mycolates to host-derived glucose. Specific T cell
recognition of an epitope formed by interaction of host and pathogen biosynthetic
pathways provides a mechanism for immune response to those pathogenic
mycobacteria that have productively infected tissues, as distinguished from
ubiquitous, but innocuous, environmental mycobacteria.
PMID- 11015439
TI - Interferon gamma signaling alters the function of T helper type 1 cells.
AB - One mechanism regulating the ability of different subsets of T helper (Th) cells
to respond to cytokines is the differential expression of cytokine receptors. For
example, Th2 cells express both chains of the interferon gamma receptor (IFN
gammaR), whereas Th1 cells do not express the second chain of the IFN-gammaR (IFN
gammaR2) and are therefore unresponsive to IFN-gamma. To determine whether the
regulation of IFN-gammaR2 expression, and therefore IFN-gamma responsiveness, is
important for the differentiation of naive CD4(+) T cells into Th1 cells or for
Th1 effector function, we generated mice in which transgenic (TG) expression of
IFN-gammaR2 is controlled by the CD2 promoter and enhancer. CD4(+) T cells from
IFN-gammaR2 TG mice exhibit impaired Th1 polarization potential in vitro. TG mice
also display several defects in Th1-dependent immunity in vivo, including
attenuated delayed-type hypersensitivity responses and decreased antigen-specific
IFN-gamma production. In addition, TG mice mount impaired Th1 responses against
Leishmania major, as manifested by increased parasitemia and more severe lesions
than their wild-type littermates. Together, these data suggest that the sustained
expression of IFN-gammaR2 inhibits Th1 differentiation and function. Therefore,
the acquisition of an IFN-gamma-unresponsive phenotype in Th1 cells plays a
crucial role in the development and function of these cells.
PMID- 11015440
TI - Tec family kinases modulate thresholds for thymocyte development and selection.
AB - Tec family kinases are implicated in T cell receptor (TCR) signaling, and
combined mutation of inducible T cell kinase (Itk) and resting lymphocyte kinase
(Rlk)/Txk in mice dramatically impairs mature T cell function. Nonetheless,
mutation of these kinases still permits T cell development. While itk(-)(/)- mice
exhibit mild reductions in T cells with decreased CD4/CD8 cell ratios, rlk(-)(/)
itk(-)(/)- mice have improved total T cell numbers yet maintain decreased CD4/CD8
ratios. Using TCR transgenics and an in vitro thymocyte deletion model, we
demonstrate that mutation of Tec kinases causes graded defects in thymocyte
selection, leading to a switch from negative to positive selection in rlk(-)(/)
itk(-)(/)- animals. The reduction in both positive and negative selection and
decreased CD4/CD8 ratios correlates with decreased biochemical parameters of TCR
signaling, specifically defects in capacitive Ca(2+) influx and activation of the
mitogen-activated kinases extracellular signal-regulated kinase 1 and 2. Thus,
Tec kinases influence cell fate determination by modulating TCR signaling,
leading to altered thresholds for thymocyte selection. These results provide
support for a quantitative model for thymic development and provide evidence that
defects in negative selection can substantially alter thymic cellularity.
PMID- 11015441
TI - Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying
induction of the mitochondrial permeability transition in cardiac myocytes.
AB - We sought to understand the relationship between reactive oxygen species (ROS)
and the mitochondrial permeability transition (MPT) in cardiac myocytes based on
the observation of increased ROS production at sites of spontaneously deenergized
mitochondria. We devised a new model enabling incremental ROS accumulation in
individual mitochondria in isolated cardiac myocytes via photoactivation of
tetramethylrhodamine derivatives, which also served to report the mitochondrial
transmembrane potential, DeltaPsi. This ROS accumulation reproducibly triggered
abrupt (and sometimes reversible) mitochondrial depolarization. This phenomenon
was ascribed to MPT induction because (a) bongkrekic acid prevented it and (b)
mitochondria became permeable for calcein ( approximately 620 daltons)
concurrently with depolarization. These photodynamically produced "triggering"
ROS caused the MPT induction, as the ROS scavenger Trolox prevented it. The time
required for triggering ROS to induce the MPT was dependent on intrinsic cellular
ROS-scavenging redox mechanisms, particularly glutathione. MPT induction caused
by triggering ROS coincided with a burst of mitochondrial ROS generation, as
measured by dichlorofluorescein fluorescence, which we have termed mitochondrial
"ROS-induced ROS release" (RIRR). This MPT induction/RIRR phenomenon in cardiac
myocytes often occurred synchronously and reversibly among long chains of
adjacent mitochondria demonstrating apparent cooperativity. The observed link
between MPT and RIRR could be a fundamental phenomenon in mitochondrial and cell
biology.
PMID- 11015442
TI - Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell
apoptosis.
AB - Heme oxygenase 1 (HO-1) inhibits apoptosis by regulating cellular prooxidant
iron. We now show that there is an additional mechanism by which HO-1 inhibits
apoptosis, namely by generating the gaseous molecule carbon monoxide (CO).
Overexpression of HO-1, or induction of HO-1 expression by heme, protects
endothelial cells (ECs) from apoptosis. When HO-1 enzymatic activity is blocked
by tin protoporphyrin (SnPPIX) or the action of CO is inhibited by hemoglobin
(Hb), HO-1 no longer prevents EC apoptosis while these reagents do not affect the
antiapoptotic action of bcl-2. Exposure of ECs to exogenous CO, under inhibition
of HO-1 activity by SnPPIX, substitutes HO-1 in preventing EC apoptosis. The
mechanism of action of HO-1/CO is dependent on the activation of the p38 mitogen
activated protein kinase (MAPK) signaling transduction pathway. Expression of HO
1 or exposure of ECs to exogenous CO enhanced p38 MAPK activation by TNF-alpha.
Specific inhibition of p38 MAPK activation by the pyridinyl imidazol SB203580 or
through overexpression of a p38 MAPK dominant negative mutant abrogated the
antiapoptotic effect of HO-1. Taken together, these data demonstrate that the
antiapoptotic effect of HO-1 in ECs is mediated by CO and more specifically via
the activation of p38 MAPK by CO.
PMID- 11015443
TI - Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member
leads to negative regulation of lymphocyte activation.
AB - PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and
myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance
and demonstrate multiple autoimmune features. We report here that the ligand of
PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads
to the inhibition of T cell receptor-mediated lymphocyte proliferation and
cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal
levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting
cells, including human peripheral blood monocytes stimulated with interferon
gamma, and activated human and murine dendritic cells. In addition, PD-L1 is
expressed in nonlymphoid tissues such as heart and lung. The relative levels of
inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells
may determine the extent of T cell activation and consequently the threshold
between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and
its potential interaction with PD-1 may subsequently determine the extent of
immune responses at sites of inflammation.
PMID- 11015444
TI - Salmonella-induced caspase-2 activation in macrophages: a novel mechanism in
pathogen-mediated apoptosis.
AB - The enterobacterial pathogen Salmonella induces phagocyte apoptosis in vitro and
in vivo. These bacteria use a specialized type III secretion system to export a
virulence factor, SipB, which directly activates the host's apoptotic machinery
by targeting caspase-1. Caspase-1 is not involved in most apoptotic processes but
plays a major role in cytokine maturation. We show that caspase-1-deficient
macrophages undergo apoptosis within 4-6 h of infection with invasive bacteria.
This process requires SipB, implying that this protein can initiate the apoptotic
machinery by regulating components distinct from caspase-1. Invasive Salmonella
typhimurium targets caspase-2 simultaneously with, but independently of, caspase
1. Besides caspase-2, the caspase-1-independent pathway involves the activation
of caspase-3, -6, and -8 and the release of cytochrome c from mitochondria, none
of which occurs during caspase-1-dependent apoptosis. By using caspase-2 knockout
macrophages and chemical inhibition, we establish a role for caspase-2 in both
caspase-1-dependent and -independent apoptosis. Particularly, activation of
caspase-1 during fast Salmonella-induced apoptosis partially relies on caspase-2.
The ability of Salmonella to induce caspase-1-independent macrophage apoptosis
may play a role in situations in which activation of this protease is either
prevented or uncoupled from the induction of apoptosis.
PMID- 11015445
TI - Recruitment of SLP-76 to the membrane and glycolipid-enriched membrane
microdomains replaces the requirement for linker for activation of T cells in T
cell receptor signaling.
AB - Two hematopoietic-specific adapters, src homology 2 domain-containing leukocyte
phosphoprotein of 76 kD (SLP-76) and linker for activation of T cells (LAT), are
critical for T cell development and T cell receptor (TCR) signaling. Several
studies have suggested that SLP-76 and LAT function coordinately to promote
downstream signaling. In support of this hypothesis, we find that a fraction of
SLP-76 localizes to glycolipid-enriched membrane microdomains (GEMs) after TCR
stimulation. This recruitment of SLP-76 requires amino acids 224-244. The
functional consequences of targeting SLP-76 to GEMs for TCR signaling are
demonstrated using a LAT/SLP-76 chimeric protein. Expression of this construct
reconstitutes TCR-inducted phospholipase Cgamma1 phosphorylation, extracellular
signal-regulated kinase activation, and nuclear factor of activated T cells
(NFAT) promoter activity in LAT-deficient Jurkat T cells (J.CaM2). Mutation of
the chimeric construct precluding its recruitment to GEMs diminishes but does not
eliminate its ability to support TCR signaling. Expression of a chimera that
lacks SLP-76 amino acids 224-244 restores NFAT promoter activity, suggesting that
if localized, SLP-76 does not require an association with Gads to promote T cell
activation. In contrast, mutation of the protein tyrosine kinase phosphorylation
sites of SLP-76 in the context of the LAT/SLP-76 chimera abolishes reconstitution
of TCR function. Collectively, these experiments show that optimal TCR signaling
relies on the compartmentalization of SLP-76 and that one critical function of
LAT is to bring SLP-76 and its associated proteins to the membrane.
PMID- 11015446
TI - DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes
in natural killer cells.
AB - Many of the activating receptors on natural killer (NK) cells are multisubunit
complexes composed of ligand-binding receptors that are noncovalently associated
with membrane-bound signaling adaptor proteins, including CD3zeta,
FcstraightepsilonRIgamma, DAP12, and DAP10. Because the DAP10 and DAP12 genes are
closely linked, expressed in NK cells, and have remarkably similar transmembrane
segments, it was of interest to determine the specificity of their interactions
with ligand-binding receptors and to examine their signaling properties. Despite
their similarities, DAP10, DAP12, FcstraightepsilonRIgamma, and CD3zeta form
specific receptor complexes with their ligand-binding partners in NK cells and
transfectants. The transmembrane regions of DAP10 and DAP12 are sufficient to
confer specific association with their partners. Although cross-linking of either
DAP10- or DAP12-associated receptors has been shown to be sufficient to trigger
NK cell-mediated cytotoxicity against Fc receptor-bearing cells, substantial
synergy was observed in the induction of cytokine production when both receptors
were engaged. Activation of the Syk/ZAP70 tyrosine kinases by the immunoreceptor
tyrosine-based activation motif-containing DAP12 adaptor and of the
phosphatidylinositol 3-kinase pathway by the YxNM-containing DAP10 adaptor may
play an important role in the stimulation of NK cells and T cells.
PMID- 11015447
TI - LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes
formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human
peripheral blood neutrophils, monocytes, and T cells.
AB - We have previously shown that antimicrobial peptides like defensins have the
capacity to mobilize leukocytes in host defense. LL-37 is the cleaved
antimicrobial 37-residue, COOH-terminal peptide of hCAP18 (human cationic
antimicrobial protein with a molecular size of 18 kD), the only identified member
in humans of a family of proteins called cathelicidins. LL-37/hCAP18 is produced
by neutrophils and various epithelial cells. Here we report that LL-37 is
chemotactic for, and can induce Ca(2+) mobilization in, human monocytes and
formyl peptide receptor-like 1 (FPRL1)-transfected human embryonic kidney 293
cells. LL-37-induced Ca(2+) mobilization in monocytes can also be cross
desensitized by an FPRL1-specific agonist. Furthermore, LL-37 is also chemotactic
for human neutrophils and T lymphocytes that are known to express FPRL1. Our
results suggest that, in addition to its microbicidal activity, LL-37 may
contribute to innate and adaptive immunity by recruiting neutrophils, monocytes,
and T cells to sites of microbial invasion by interacting with FPRL1.
PMID- 11015448
TI - Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC
chemokine receptor (CCR)2.
AB - Monocyte recruitment to the central nervous system (CNS) is a necessary step in
the development of pathologic inflammatory lesions in experimental autoimmune
encephalomyelitis (EAE), a murine model of multiple sclerosis. Monocyte
chemoattractant protein (MCP)-1, a potent agonist for directed monocyte
migration, has been implicated in the pathogenesis of EAE. Here we report that
deficiency in CC chemokine receptor (CCR)2, the receptor for MCP-1, confers
resistance to EAE induced with a peptide derived from myelin oligodendrocyte
glycoprotein peptide 35-55 (MOGp35-55). CCR2(-/)- mice immunized with MOGp35-55
failed to develop mononuclear cell inflammatory infiltrates in the CNS and failed
to increase CNS levels of the chemokines RANTES (regulated on activation, normal
T cell expressed and secreted), MCP-1, and interferon (IFN)-inducible protein 10
(IP-10) as well the chemokine receptors CCR1, CCR2, and CCR5. Additionally, T
cells from CCR2(-/)- immunized mice showed decreased antigen-induced
proliferation and production of IFN-gamma compared with wild-type immunized
controls, suggesting that CCR2 enhances the T helper cell type 1 immune response
in EAE. These data indicate that CCR2 plays a necessary and nonredundant role in
the pathogenesis of EAE.
PMID- 11015450
TI - Sporadic primary pulmonary hypertension is associated with germline mutations of
the gene encoding BMPR-II, a receptor member of the TGF-beta family.
AB - BACKGROUND: Primary pulmonary hypertension (PPH), resulting from occlusion of
small pulmonary arteries, is a devastating condition. Mutations of the bone
morphogenetic protein receptor type II gene (BMPR2), a component of the
transforming growth factor beta (TGF-beta) family which plays a key role in cell
growth, have recently been identified as causing familial PPH. We have searched
for BMPR2 gene mutations in sporadic PPH patients to determine whether the same
genetic defect underlies the more common form of the disorder. METHODS: We
investigated 50 unrelated patients, with a clinical diagnosis of PPH and no
identifiable family history of pulmonary hypertension, by direct sequencing of
the entire coding region and intron/exon boundaries of the BMPR2 gene. DNA from
available parent pairs (n=5) was used to assess the occurrence of spontaneous (de
novo) mutations contributing to sporadic PPH. RESULTS: We found a total of 11
different heterozygous germline mutations of the BMPR2 gene in 13 of the 50 PPH
patients studied, including missense (n=3), nonsense (n=3), and frameshift (n=5)
mutations each predicted to alter the cell signalling response to specific
ligands. Parental analysis showed three occurrences of paternal transmission and
two of de novo mutation of the BMPR2 gene in sporadic PPH. CONCLUSION: The
sporadic form of PPH is associated with germline mutations of the gene encoding
the receptor protein BMPR-II in at least 26% of cases. A molecular classification
of PPH, based upon the presence or absence of BMPR2 mutations, has important
implications for patient management and screening of relatives.
PMID- 11015449
TI - Channelopathies: ion channel defects linked to heritable clinical disorders.
AB - Electrical signals are critical for the function of neurones, muscle cells, and
cardiac myocytes. Proteins that regulate electrical signalling in these cells,
including voltage gated ion channels, are logical sites where abnormality might
lead to disease. Genetic and biophysical approaches are being used to show that
several disorders result from mutations in voltage gated ion channels.
Understanding gained from early studies on the pathogenesis of a group of muscle
diseases that are similar in their episodic nature (periodic paralysis) showed
that these disorders result from mutations in a gene encoding a voltage gated
Na(+) channel. Their characterisation as channelopathies has served as a paradigm
for other episodic disorders. For example, migraine headache and some forms of
epilepsy have been shown to result from mutations in voltage gated Ca(2+) channel
genes, while long QT syndrome is known to result from mutations in either K(+) or
Na(+) channel genes. This article reviews progress made in the complementary
fields of molecular genetics and cellular electrophysiology which has led to a
better understanding of voltage gated ion channelopathies in humans and mice.
PMID- 11015451
TI - ATR-X mutations cause impaired nuclear location and altered DNA binding
properties of the XNP/ATR-X protein.
AB - Mutations in the XNP/ATR-X gene, located in Xq13.3, are associated with several X
linked mental retardation syndromes, the best known being alpha thalassaemia with
mental retardation (ATR-X). The XNP/ATR-X protein belongs to the family of
SWI/SNF DNA helicases and contains three C2-C2 type zinc fingers of unknown
function. Previous studies have shown that 65% of mutations of XNP have been
found within the zinc finger domain (encoded by exons 7, 8, and the beginning of
exon 9) while 35% of the mutations have been found in the helicase domain
extending over 3 kb at the C-terminus of the protein. Although different types of
mutations have been identified, no specific genotype-phenotype correlation has
been found, suggesting that gene alteration leads to a loss of function
irrespective of mutation type. Our aims were to understand the function of the
XNP/ATR-X protein better, with specific attention to the functional consequences
of mutations to the zinc finger domain. We used monoclonal antibodies directed
against the XNP/ATR-X protein and performed immunocytochemical and western blot
analyses, which showed altered or absent XNP/ATR-X expression in cells of
affected patients. In addition, we used in vitro experiments to show that the
zinc finger domain can mediate double stranded DNA binding and found that the DNA
binding capacity of mutant forms in ATR-X patients is severely reduced. These
data provide insights into the understanding of the functional significance of
XNP/ATR-X mutations.
PMID- 11015452
TI - Divergent outcomes of intrachromosomal recombination on the human Y chromosome:
male infertility and recurrent polymorphism.
AB - The Y chromosome provides a unique opportunity to study mutational processes
within the human genome, decoupled from the confounding effects of
interchromosomal recombination. It has been suggested that the increased density
of certain dispersed repeats on the Y could account for the high frequency of
causative microdeletions relative to single nucleotide mutations in infertile
males. Previously we localised breakpoints of an AZFa microdeletion close to two
highly homologous complete human endogenous retroviral sequences (HERV),
separated by 700 kb. Here we show, by sequencing across the breakpoint, that the
microdeletion occurs in register within a highly homologous segment between the
HERVs. Furthermore, we show that recurrent double crossovers have occurred
between the HERVs, resulting in the loss of a 1.5 kb insertion from one HERV, an
event underlying the first ever Y chromosomal polymorphism described, the 12f2
deletion. This event produces a substantially longer segment of absolute homology
and as such may result in increased predisposition to further intrachromosomal
recombination. Intrachromosomal crosstalk between these two HERV sequences can
thus result in either homogenizing sequence conversion or a microdeletion causing
male infertility. This represents a major subclass of AZFa deletions.
PMID- 11015453
TI - Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic
paraparesis.
AB - BACKGROUND: Hereditary spastic paraparesis is a genetically heterogeneous
condition. Recently, mutations in the spastin gene were reported in families
linked to the common SPG4 locus on chromosome 2p21-22. OBJECTIVES: To study a
population of patients with hereditary spastic paraparesis for mutations in the
spastin gene (SPG4) on chromosome 2p21-22. METHODS: DNA from 32 patients (12 from
families known to be linked to SPG4) was analysed for mutations in the spastin
gene by single strand conformational polymorphism analysis and sequencing. All
patients were also examined clinically. RESULTS: Thirteen SPG4 mutations were
identified, 11 of which are novel. These mutations include missense, nonsense,
frameshift, and splice site mutations, the majority of which affect the AAA
cassette. We also describe a nucleotide substitution outside this conserved
region which appears to behave as a recessive mutation. CONCLUSIONS: Recurrent
mutations in the spastin gene are uncommon. This reduces the ease of mutation
detection as a part of the diagnostic work up of patients with hereditary spastic
paraparesis. Our findings have important implications for the presumed function
of spastin and schemes for mutation detection in HSP patients.
PMID- 11015454
TI - Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) gene
interactions with the apolipoprotein E epsilon4 allele as risk factors in
Alzheimer's disease and in Parkinson's disease with coexisting Alzheimer
pathology.
AB - Alzheimer's disease (AD) and Parkinson's disease (PD) are genetically
heterogeneous. Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase
(BCHE) genes may modify the risk of these disorders. We investigated whether
common polymorphisms present in these genes operate as risk factors for AD and PD
in Finnish subjects, independently or in concert with the apolipoprotein E
epsilon4 allele (APOE epsilon4). Eighty late onset sporadic AD patients, 53 PD
patients (34 of whom had concomitant AD pathology), and 67 control subjects were
genotyped for the insertion (I)/deletion (D) polymorphism of DCP1 and the K
variant of BCHE. In logistic regression analysis, the DCP1 *I allele in
combination with APOE epsilon4 significantly increased the risk of AD (OR 30.0,
95% CI 7.3-123.7), compared to subjects carrying neither of the alleles. Similar
analysis showed that the risk of AD was significantly increased in subjects
carrying both the BCHE wild type (*WT/*WT) genotype and epsilon4 (OR 9.9, 95% CI
2.9-33.8), compared to those without this BCHE genotype and epsilon4. Further,
the risk of PD with AD pathology was significantly increased for carriers of DCP1
*I and epsilon4 (OR 8.0, 95% CI 2.1-31.1). We thus conclude that, in Finns,
interaction between DCP1 *I and epsilon4 increases the risk of AD as well as of
PD with coexisting Alzheimer pathology, which underlines the importance of the
DCP1 I/D polymorphism in the development of Alzheimer neuropathology, whereas the
wild type BCHE genotype in combination with epsilon4 had a combined effect with
regard to the risk of AD.
PMID- 11015455
TI - Two translocations of chromosome 15q associated with dyslexia.
AB - Developmental dyslexia is characterised by difficulties in learning to read. As
reading is a complex cognitive process, multiple genes are expected to contribute
to the pathogenesis of dyslexia. The genetics of dyslexia has been a target of
molecular studies during recent years, but so far no genes have been identified.
However, a locus for dyslexia on chromosome 15q21 (DYX1) has been established in
previous linkage studies. We have identified two families with balanced
translocations involving the 15q21-q22 region. In one family, the translocation
segregates with specific dyslexia in three family members. In the other family,
the translocation is associated with dyslexia in one family member. We have
performed fluorescence in situ hybridisation (FISH) studies to refine the
position of the putative dyslexia locus further. Our results indicate that both
translocation breakpoints on 15q map within an interval of approximately 6-8 Mb
between markers D15S143 and D15S1029, further supporting the presence of a locus
for specific dyslexia on 15q21.
PMID- 11015456
TI - Two common forms of the human MLH1 gene may be associated with functional
differences.
PMID- 11015457
TI - FMR3 is a novel gene associated with FRAXE CpG island and transcriptionally
silent in FRAXE full mutations.
AB - We have identified a novel gene, FMR3, originating from the FRAXE CpG island. The
FMR3 gene is transcribed from the opposite strand to the FMR2 gene. Analogous to
the silencing of the FMR1 and FMR2 genes, FMR3 transcription is extinguished by
FRAXE full mutation. Although the role of FMR3 in FRAXE associated mild to
borderline mental retardation is not yet clear, lack of expression of FMR3 in
FRAXE full mutation males means that the FMR3 gene is potentially involved.
PMID- 11015458
TI - Genetics and deafness: what do families want?
PMID- 11015459
TI - A case of dyschondrosteosis from Roman Britain.
PMID- 11015460
TI - Xp;Yp translocation inherited from the father in an SRY, RBM, and TSPY positive
true hermaphrodite with oligozoospermia.
PMID- 11015461
TI - MPS II in females: molecular basis of two different cases.
PMID- 11015462
TI - Partial tetrasomy 21 in a male infant.
PMID- 11015463
TI - Benign familial infantile convulsions: report of a UK family and confirmation of
genetic heterogeneity.
PMID- 11015464
TI - Low frequency of microsatellite instability in BRCA1 mutated breast tumours.
PMID- 11015465
TI - Effects of tea consumption on nutrition and health.
AB - Beneficial health effects of tea have been demonstrated in animal experiments and
some human studies. The two most extensively investigated diseases are cancer and
heart disease. Although mechanisms of protective activity of tea against these
diseases have been proposed, there are inconsistencies in the relationship
between tea consumption and the risk of these diseases in humans. The
bioavailability of active components is beginning to be understood, but further
research is required to determine whether the results from animal studies are
applicable to humans. Also discussed are the possible effects of tea in
increasing thermogenesis and bone density as well as decreasing risk of cataracts
and arthritis. The potential health benefits of tea consumption warrant further
investigation.
PMID- 11015466
TI - Leucine stimulates translation initiation in skeletal muscle of postabsorptive
rats via a rapamycin-sensitive pathway.
AB - The objectives of the present study were twofold: 1) to determine whether leucine
is unique among the branched-chain amino acids (BCAA) in its ability to stimulate
protein synthesis in skeletal muscle of food-deprived rats; and 2) to investigate
whether changes in muscle protein synthesis after leucine administration involve
a signaling pathway that includes the protein kinase mammalian target of
rapamycin (mTOR). In the first set of experiments, food-deprived (18 h) male rats
(200 g) were orally administered saline or 270 mg valine, isoleucine or leucine.
In the second set of experiments, food-deprived rats were injected intravenously
with rapamycin (0.75 mg/kg), a specific inhibitor of mTOR, before leucine
administration. Only leucine stimulated protein synthesis in skeletal muscle
above saline-treated controls (P: < 0.05). Furthermore, leucine was most
effective among the BCAA at enhancing phosphorylation of eukaryotic initiation
factor (eIF), 4E binding protein 1 (4E-BP1) and the 70-kDa ribosomal protein S6
kinase (S6K1). Leucine-dependent hyperphosphorylation of 4E-BP1 increased the
availability of eIF4E to form the active eIF4G.eIF4E complex. To a lesser extent,
isoleucine also enhanced phosphorylation of 4E-BP1 and S6K1. Rapamycin inhibited
protein synthesis in both leucine-treated and food-deprived rats. Additionally,
rapamycin prevented the stimulatory effects of leucine on eIF4E availability for
binding eIF4G and inhibited leucine-dependent phosphorylation of S6K1. The data
demonstrate that leucine is unique among the BCAA in its ability to stimulate
protein synthesis in muscle of food-deprived rats. We show for the first time
that leucine-dependent stimulation of translation initiation in vivo occurs via a
rapamycin-sensitive pathway.
PMID- 11015467
TI - Palm tocotrienols protect ApoE +/- mice from diet-induced atheroma formation.
AB - We evaluated the effects of vitamin E and beta-carotene on apolipoprotein (apo)E
+/- female mice, which develop atherosclerosis only when fed diets high in
triglyceride and cholesterol. Mice were fed a nonpurified control diet (5.3 g/100
g triglyceride, 0.2 g/100 g cholesterol), an atherogenic diet alone (15.8 g/100 g
triglyceride, 1.25 g/100 g cholesterol, 0.5 g/100 g Na cholate) or the
atherogenic diet supplemented with either 0.5 g/100 g (+)-alpha-tocopherol (mixed
isomers); 0.5 g/100 g palm tocopherols (palm-E; 33% alpha-tocopherol, 16.1% alpha
tocotrienol, 2.3% beta-tocotrienol, 32.2% gamma-tocotrienol, 16.1% delta
tocotrienol); 1.5 g/100 g palm-E; or 0.01 g/100 g palm-carotenoids (58% beta
carotene, 33% alpha-carotene, 9% other carotenoids). Compared with mice fed the
control diet, plasma cholesterol was fourfold greater in mice fed the atherogenic
diet. Mice fed the 1.5 g/100 g palm-E supplement had 60% lower plasma cholesterol
than groups fed the other atherogenic diets. Mice fed the atherogenic diet had
markedly higher VLDL, intermediate density lipoprotein (IDL) and LDL cholesterol
and markedly lower HDL cholesterol than the controls. Lipoprotein patterns in
mice supplemented with alpha-tocopherol or palm carotenoids were similar to those
of the mice fed the atherogenic diet alone, but the pattern in mice supplemented
with 1. 5 g/100 g palm-E was similar to that of mice fed the control diet. In
mice fed the atherogenic diet, the hepatic cholesterol plus cholesterol ester
concentration was 4.4-fold greater than in mice fed the control diet.
Supplementing with 1.5 g/100 g palm-E lowered hepatic cholesterol plus
cholesterol ester concentration 66% compared with the atherogenic diet alone.
Mice fed the atherogenic diet had large atherosclerotic lesions at the level of
the aortic valve. With supplements of 0.5 g/100 g palm-E or 1.5 g/100 g palm-E,
the size of the lesions was 92 or 98% smaller, respectively. The 0.5 g/100 g
alpha-tocopherol and palm carotenoid supplements had no effect. Supplements did
not alter mRNA abundance for apolipoproteins A1, E, and C3. The beneficial effect
of tocotrienols on atherogenesis, the plasma lipoprotein profile and accumulation
of hepatic cholesterol esters cannot be attributed to their antioxidant
properties.
PMID- 11015468
TI - Dietary fat modulates serum paraoxonase 1 activity in rats.
AB - We examined the effects of dietary fats with specific fatty acid compositions, on
serum paraoxonase (PON1) activity in rats. Male adult Sprague-Dawley rats were
divided randomly into four dietary groups. One group received the control diet
[AIN 93M with soybean oil (5 g/100 g diet)], whereas the remaining three groups
received the modified control diet supplemented with (15 g/100 g diet) triolein,
tripalmitin or fish oil, respectively. After 20 d, blood was obtained after
overnight food deprivation and PON1 activity was determined. Serum lipids and
lipid components of lipoproteins were also determined. Serum PON1 activity
[micromol/(L.min)] was significantly (P: < 0.05) higher in triolein (98 +/- 6)
and lower in fish oil (41 +/- 4), compared with tripalmitin-fed rats (63 +/- 11).
Serum PON1 activity in tripalmitin-fed rats was comparable to that of controls
(67 +/- 9). Serum PON1 activity correlated significantly with serum
lecithin:cholesterol acyltransferase (LCAT) activity (r = 0.77, P: < 0.001) and
was transported in blood principally in association with the denser subfraction
of HDL, very high density lipoprotein (VHDL; d > 1.15 kg/L). Serum PON1 activity
correlated strongly with serum lipids as well as lipids of VLDL, HDL and its
subfractions. Multiple linear regression analysis, however, showed a significant
relationship of serum PON1 activity, principally with the phospholipids of VHDL
(r = 0.47, P: < 0.002). These data suggest that the modulation of serum PON1
activity by dietary fat may be mediated via the effect of the specific fatty
acids on the synthesis and secretion of VHDL, the subfraction of HDL that
transports the majority of PON1 in the blood.
PMID- 11015469
TI - Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated
linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice.
AB - We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is
antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal
tumorigenesis. Only a few studies have evaluated the effects of dietary fatty
acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal
model and none have evaluated the previously touted antitumorigenicity of alpha
linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)],
or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the
Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not
been evaluated previously for antitumorigenic efficacy. This study was undertaken
to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA,
DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100
g in the diets of APC:(Min/+) mice and to determine whether any alterations in
tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor
multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA
compared with controls, whereas less pronounced effects were observed in mice fed
DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although
lower tumor numbers coincided with significantly lower prostaglandin levels in
SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low
prostaglandin levels, despite proving less efficacious with regard to tumor
number. Prostaglandin levels did not differ significantly in the CLA and GLA
groups compared with controls. These results suggest that SDA and EPA attenuate
tumorigenesis in this model and that this effect may be related in part to
alterations in prostaglandin biosynthesis.
PMID- 11015470
TI - Acute starvation and subsequent refeeding affect lymphocyte subsets and
proliferation in cats.
AB - Although the early identification of patients with suboptimal nutritional status
can allow the implementation of nutritional intervention to enhance the ability
of the body to fight infection and disease, currently no definitive test of
nutritional status exists. Therefore, this study was conducted to identify
possible functional indicators of acute nutritional deprivation. The effects of
total nutritional deprivation and subsequent refeeding on lymphocyte functions
and subpopulations were examined in 23 healthy cats. Peripheral blood samples
were analyzed at various times during food deprivation and refeeding periods.
During the food deprivation period, decreases were observed in leukocyte number
(P: < 0.05), lymphocyte number (P: < 0.05), percentage of CD4(+) cells [before
stimulation with concanavalin-A (Con-A); P: < 0.05] and the CD4/CD8 ratio (before
stimulation with Con-A; P: < 0.01) compared with d 0. Increases were observed in
the percentage of CD8(+) cells [before (P: < 0.05) and after (P: < 0.01)
stimulation with Con-A] and in intracellular calcium (P: < 0.01) during acute
starvation. During the refeeding period, increases were observed in the
percentage of CD4(+) cells (before and after stimulation with Con-A; P: < 0.01),
the percentage of CD8(+) cells (before stimulation with Con-A; P: < 0.05) and
lymphocyte number (P: < 0.05) compared with d 7. Lymphocyte proliferative
capacity tended to decrease (P: = 0.07) during starvation and increased (P: <
0.01) during the refeeding period. These findings suggest that a 7-d starvation
period had immunosuppressive effects on cats and that these effects were not
completely normalized during 7 d of refeeding. CD4(+)/CD8(+) subset alterations
and CD4/CD8 ratio in conjunction with lymphocyte proliferation may be useful as
indices of nutritional status.
PMID- 11015471
TI - Fats infused intraduodenally affect the postprandial secretion of the exocrine
pancreas and the plasma concentration of cholecystokinin but not of peptide YY in
growing pigs.
AB - In pigs, the spontaneous secretion of the exocrine pancreas and the release of
cholecystokinin (CCK) and peptide YY (PYY) after intraduodenal infusion of fully
saturated synthetic fats differing in chain length was studied. Growing pigs (n =
6) were prepared with pancreatic duct catheters, duodenal T-cannulas and
catheters placed in the jugular vein. The pigs were fed 2 g/100 g body twice
daily. Beginning with the morning feeding, a medium-chain triglyceride (MCT:
glycerol tricaprylate), a long-chain triglyceride (LCT: glycerol tristearate) or
saline was infused at a rate of 0.1 g/100 g body. Pancreatic juice was collected,
beginning 1 h preprandially until 3 h postprandially. Blood samples were obtained
15 min preprandially and 15, 45, 90 and 150 min postprandially. The infusion of
MCT evoked a change in the trend of the curve for the volume of secretion of
pancreatic juice, lipase and colipase concentrations and outputs. The trend of
the curve did not change over time for CCK and PYY. Differences between the
trends of the curves for the saline and MCT treatment were observed for volume of
secretion, protein output, lipase content and output, trypsin and colipase
output. Differences in the trends of the curves between MCT and LCT were obtained
for the outputs of protein, lipase and colipase. Plasma CCK levels were lower as
a result of the MCT treatment compared with the saline and LCT treatments. The
results suggest an immediate, distinguished response of the porcine exocrine
pancreas to fats differing in chain length.
PMID- 11015472
TI - Dietary fructans modulate polyamine concentration in the cecum of rats.
AB - Nondigestible but fermentable dietary fructans such as oligofructose exert many
effects on gut physiology through their fermentation end products such as short
chain fatty acids. Could other metabolites be produced in the gut and contribute
to the physiologic effects of dietary fructans? The aim of the study was to
evaluate the influence of oligofructose on putrescine, spermidine and spermine
concentrations in the cecum, the portal vein and the liver of rats and to assess
their involvement in cecal enlargement and the modulation of hepatic lipid
metabolism. Putrescine, spermidine and spermine were quantified by HPLC in
samples obtained from male Wistar rats fed a nonpurified standard diet (controls)
or the same diet enriched with 10 g/100 g oligofructose (OFS) for 4 wk. OFS-fed
rats had significantly greater cecal content and tissue weights. OFS almost
doubled the concentration of putrescine in the cecal contents. The concentration
of all three polyamines in the cecal tissue was significantly greater than in
controls. The concentration of spermidine in portal plasma was lower in rats fed
OFS, whereas the treatment did not affect the polyamine concentrations in the
liver. The fermentation of dietary fructans contributed to an increase in the
concentration of putrescine in the gut without modifying putrescine concentration
in either the portal blood or liver. Moreover, the greater levels of polyamines
in cecal tissue may be related to the cell proliferation resulting from OFS
fermentation in the gut.
PMID- 11015473
TI - Food deprivation increases alpha(2)-adrenoceptor-mediated modulation of jejunal
epithelial transport in young and adult rats.
AB - This study examined the effect of food deprivation on the jejunal response to
alpha(2)-adrenoceptor activation in young (20-d-old) and adult (60-d-old) rats,
using short-circuit (I(sc)) measurements in the absence or presence of furosemide
(1 mmol/L). The effect of alpha(2)-adrenoceptor stimulation by 5-bromo-N:-(4, 5
dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304; 0.3-3000 nmol/L) was a
concentration-dependent decrease in I(sc) with similar half-maximal effective
concentration (EC(50); 12.3 +/- 1.1 vs. 9.6 +/- 1.1 nmol/L) and maximal effect
(E(max); 70.6 +/- 6.9 vs. 80.6 +/- 4.5% of reduction) values in adult food
deprived and fed rats. The effect of UK 14,304 on I(sc) in fed and food-deprived
rats was markedly (P: < 0.05) attenuated by furosemide (1 mmol/L). E(max) values
for UK 14,304 in 20-d-old food-deprived rats were higher (P: < 0.05) than those
observed in fed rats (93.3 +/- 3.3 vs. 67.0 +/- 11.3% of reduction), without
differences in EC(50) values. The effect of UK 14,304 on I(sc) in 20-d-old fed
rats was completely abolished by furosemide (1 mmol/L). In food-deprived young
rats, the effect of UK 14,304 was also markedly (P: < 0.05) antagonized by
furosemide, but not completely abolished. Specific [(3)H]-rauwolscine binding in
membranes from jejunal epithelial cells revealed the presence of a single class
of binding sites, with an apparent K:(D) in the low nmol/L range. In 20-d-old
food-deprived rats, specific [(3)H]-rauwolscine binding was markedly increased,
and this was reversed by refeeding. Na(+),K(+)-ATPase activity in isolated
jejunal epithelial cells from 60-d-old fed rats was twice that in 20-d-old fed
rats [117 +/- 14 vs. 52 +/- 5 nmol free inorganic phosphorus/(mg protein.min)].
Food deprivation in adult rats, but not in 20-d-old rats, was accompanied by a
significant decrease in Na(+),K(+)-ATPase activity. In both young and adult rats
(fed and food-deprived), UK 14,304 did not affect Na(+),K(+)-ATPase activity. In
conclusion, food deprivation in 20-d-old rats enhanced the response to alpha(2)
adrenoceptor stimulation. This effect, which depends primarily on the stimulation
of a furosemide-sensitive antisecretory mechanism, is suggested to result from
increases in the number of jejunal epithelial alpha(2)-adrenoceptors.
PMID- 11015474
TI - Kinetics of carnitine palmitoyltransferase-I are altered by dietary variables and
suggest a metabolic need for supplemental carnitine in young pigs.
AB - To examine the kinetics of carnitine palmitoyltransferase-I (CPT-I) and the
influence of dietary variables, young pigs (18 kg, n = 20) were fed corn-soybean
meal diets supplemented with 40 g soy oil/kg and containing either 136 or 180 g
crude protein/kg and either 0 or 500 mg/kg L-carnitine (2 x 2 factorial design).
Diets were offered for 10 d (85% of ad libitum); CPT-I activities in liver and
skeletal muscle mitochondria were determined, and enzyme kinetic constants
(V:(max) and K:(m) for carnitine) were estimated. Kinetics of CPT-I in muscle
were not affected by diet (P: > 0.1; carnitine K:(m) = 480 +/- 44 micromol/L). In
contrast, the K:(m) for carnitine in liver was increased from 164 to 216 +/- 20
micromol/L by dietary L-carnitine supplementation (P: < 0.01) and from 169 to 211
+/- 20 micromol/L by high protein feeding (P: < 0.05). Dietary L-carnitine
increased muscle and liver free carnitine concentrations by 72 and 158% over
control concentrations (770 and 80 micro;mol/kg wet muscle and liver,
respectively). Because tissue carnitine concentrations were within the range of
the respective K:(m) for both liver and muscle tissue, it is inferred that
alteration of tissue carnitine concentrations via dietary supplementation could
modulate CPT-I activity in young pigs.
PMID- 11015475
TI - Conjugated linoleic acid persistently increases total energy expenditure in AKR/J
mice without increasing uncoupling protein gene expression.
AB - AKR/J mice fed a high fat diet were treated with a 1% (1 g/100 g) admixture of
conjugated linoleic acids (CLA) for 5 wk and compared with control mice. Body
weights, energy intakes and energy expenditure (EE) determined by indirect
calorimetry were measured weekly. CLA treatment reduced adipose depot weights by
approximately 50% but had no significant effects on either body weight or energy
intake. CLA increased EE persistently by an average of 7.7% throughout the 5-wk
experiment. This greater EE, despite no difference in energy intake, was
sufficient to account for the lower body fat stores in the CLA-treated mice. De
novo fatty acid biosynthesis in adipose tissue, measured by incorporation of
deuterium-labeled water, was not decreased by CLA treatment and therefore did not
explain the lower adipose lipid in these mice. Expression of uncoupling protein
(UCP) in skeletal muscle, white adipose tissue and kidney was not affected by CLA
treatment. In brown adipose tissue, UCP1 expression was not affected by CLA
treatment. However, UCP2 expression, although quite low, was significantly
greater in CLA-fed mice. We conclude that CLA acts to reduce body fat stores by
chronically increasing metabolic rate. This effect on metabolic rate is likely
not due to increased UCP gene expression. Furthermore, the reduced body fat is
not due to decreased de novo fatty acid synthesis in white adipose tissue.
PMID- 11015476
TI - Relationship between human adipose tissue agouti and fatty acid synthase (FAS).
AB - The human homologue of the murine obesity gene, agouti, is expressed in adipose
tissue. We have shown that recombinant agouti protein regulates adipocyte
lipogenesis and lipolysis coordinately and promotes lipid storage via a Ca(2+)
dependent mechanism in vitro, which may contribute to agouti-induced obesity.
However, little is known about agouti's physiologic function in humans. We first
studied the agouti content in human mature adipocytes vs. preadipocytes. The
agouti content of human mature adipocytes was five times as abundant as in
preadipocytes (19.18 +/- 2.46 vs. 4.07 +/- 0.51 pg/microg protein, P: < 0.005),
suggesting that agouti is up-regulated during adipocyte differentiation. We next
studied the relationship of agouti mRNA and protein to fatty acid synthase (FAS)
mRNA and activity in adipose tissue obtained from nonobese and mildly obese
patients (body mass index range, 21-31 kg/m(2)). Agouti protein was correlated
with FAS activity (r = 0.782, P: < 0.005). Similarly, human adipose tissue agouti
mRNA level was also correlated with FAS mRNA level (r = 0.846, P: < 0.001). These
data suggest that agouti may be another adipocyte-produced factor that modulates
adipocyte lipid metabolism via a paracrine/autocrine mechanism.
PMID- 11015477
TI - Growth hormone receptor gene expression in porcine skeletal and cardiac muscles
is selectively regulated by postnatal undernutrition.
AB - During mild postnatal undernutrition, growth hormone receptor (GHR) mRNA
abundance decreases in liver but increases in longissimus dorsi muscle. We tested
the following hypotheses: 1) GHR gene expression is related to the metabolic and
contractile characteristics of different muscles, and 2) the GHR response to
nutrition depends on muscle type. Eight pairs of littermate pigs were weaned at 3
wk and given an optimal [60 g/(kg.d)] or low [(20 g/(kg.d)] food intake for the
next 3 wk. All pigs grew, but at a slower rate in the low food intake group (P: <
0.001). Functionally distinct muscles were assessed for GHR mRNA (RNase
protection analysis), oxidative myofibers (succinate dehydrogenase
histochemistry) and type I slow myofibers (myosin immunocytochemistry). There
were striking muscle-specific differences in GHR gene expression (P: < 0.001) and
in its regulation by nutritional status. Relative expression of GHR mRNA in the
optimal food intake group occurred in ascending order as follows: longissimus <
diaphragm approximately rhomboideus < cardiac < soleus. There was a positive
correlation with the proportion of oxidative myofibers (P: < 0.001) but not with
type I myofibers (P: > 0.10). Compared with the high intake pigs, hepatic GHR
mRNA was downregulated in the low intake pigs by 59% (P: < 0.01), whereas in the
four muscles examined it was upregulated as follows: longissimus, 124% (P: <
0.05); rhomboideus, 19% (P: > 0.4); soleus, 65% (P: < 0. 05); cardiac, 51% (P: <
0.05). Moreover, the proportion of skeletal muscle fibers with high oxidative
capacity was also greater in the low intake group (P: < 0.05). We conclude that
postnatal GHR gene expression and its regulation by mild undernutrition are
related to the metabolic, contractile and specific functional properties of
different muscles.
PMID- 11015478
TI - Genistein activates apolipoprotein A-I gene expression in the human hepatoma cell
line Hep G2.
AB - Soy phytoestrogens have been shown to increase plasma levels of HDL cholesterol
and apolipoprotein (apo) A-I, its major protein component, in animal studies and
in some human studies. The human hepatoma cell line Hep G2 was used to study the
effect of the phytoestrogens genistein and daidzein on apo A-I secretion and gene
expression in liver cells. Both genistein and daidzein increased apo A-I
secretion in a dose-dependent fashion. Apo A-I concentration in the media of
treated cells was increased approximately fivefold by 10 micromol/L genistein (P:
< 0.001) and approximately onefold by 10 micromol/L daidzein (P: < 0.001)
compared with control cells. The effect of genistein on apo A-I secretion was
similar to that observed with 17-beta-estradiol. Treatment of cells with
genistein for 24 h increased the transcriptional activity of the apo A-I gene as
measured by nuclear run-on assay. Transfection experiments with plasmids
containing regulatory regions of the apo A-I gene cloned in front of the
luciferase reporter gene indicated that the 5' region of the apo A-I gene
contained between nucleotides -256 and -41 is responsible for the increased
expression of this gene by genistein.
PMID- 11015479
TI - The association between two common mutations C677T and A1298C in human
methylenetetrahydrofolate reductase gene and the risk for diabetic nephropathy in
type II diabetic patients.
AB - Mutations of the methylenetetrahydrofolate reductase (MTHFR) gene have been shown
to be associated with a predisposition to developing diabetic nephropathy (DN) in
specific populations. The frequency of two MTHFR mutations, a recently described
mutation in the human MTHFR gene A1298C and C677T, whose association with DN is
already known, was determined in an Israeli Jewish population with type 2
diabetes mellitus (DM). Both A1298C and C677T are highly prevalent in the
diabetic population with allele frequencies of 0.35 and 0.36, respectively. The
genotype frequency and allele frequency for these two polymorphisms in patients
who are normoalbuminuric (n = 55) were compared with those of patients who had
either micro- or macroalbuminuria (n = 43). For both polymorphisms, there were no
significant differences in either the genotype distribution or allele frequency
in patients with or without DN. However, in patients with serum folate <15.4
nmol/L, there was a greater incidence of DN in those patients who were homozygous
or heterozygous for the C677T mutation. For the A1298C mutation, there is
evidence suggesting that the homozygous state may be protective in patients with
low-normal serum folate. Folate supplementation in diabetic patients with the
C677T mutation and low-normal serum folate may prevent the onset or retard the
progression of DN.
PMID- 11015480
TI - Growth velocity, fat-free mass and energy intake are inversely related to viral
load in HIV-infected children.
AB - The study objectives were to assess the relationships among human
immunodeficiency virus (HIV) replication, energy balance, body composition and
growth in children with HIV-associated growth failure (GF). Energy intake and
expenditure, body composition and level of HIV RNA were measured in 16 HIV
infected children with growth failure (HIV+/GF+), defined as a 12-mo height
velocity = 5th percentile for age, and 26 HIV-infected children with normal
rates of growth (HIV+/GF-). Energy intake was measured by repeated 24-h dietary
recall, resting energy expenditure (REE) by indirect calorimetry and total energy
expenditure (TEE) by the doubly labeled water method. Fat-free mass (FFM) was
determined by dual X-ray energy absorptiometry and plasma HIV RNA by the
polymerase chain reaction method. The mean plasma HIV RNA content among the
HIV+/GF+ group was nearly 1.5 log higher than that of the HIV+/GF- group (4. 89
+/- 1.08 vs. 3.43 +/- 1.64 x10(2) copies/L, P: = 0.009). The mean daily energy
intake, and age-adjusted REE and TEE were lower in HIV+/GF+ children (P: = 0.003,
0.06 and 0.16, respectively). HIV+/GF+ children had a mean daily energy deficit
of 674 +/- 732 kJ/d compared with HIV+/GF- children who had a mean energy surplus
of 1448 +/- 515 kJ/d (P: = 0.030). There were no differences in REE after
adjustment for differences in FFM and age using multiple regression analysis (P:
= 0.88). There was a significant inverse relationship between FFM and plasma HIV
RNA [R:(2) = 0.64, standard error of the estimate (SEE) = 3.23] and between viral
load and 12-mo growth velocity (R:(2) = 0.61, SE = 1.51). Viral load and energy
intake were also inversely related (R(2) = 0.17, SEE = 573.2, P: = 0. 0125). In
HIV-infected children, rate of growth, quantity of FFM and energy intake are
closely related to the level of HIV replication. The energy intake of children
with HIV-associated GF may not be adequate for supporting normal development of
FFM and growth, despite possible decreases in total energy expenditure.
PMID- 11015481
TI - A high carbohydrate versus a high monounsaturated fatty acid diet lowers the
atherogenic potential of big VLDL particles in patients with type 1 diabetes.
AB - The objective of the present study was to compare the effects of two diets on the
atherogenic potential of two VLDL subfractions harvested from fasting subjects by
measuring the number and composition of particles and the amount of esterified
cholesterol accumulated in macrophages. A high (25%) monounsaturated fatty acid
(Mono) diet and a high (61%) carbohydrate (CHO) diet were provided for 4 wk in a
randomized crossover design to 19 normolipidemic, nonobese patients with type 1
diabetes. The two diets were matched for protein, polyunsaturated/saturated fatty
acids, cholesterol and fiber content. The number of circulating big VLDL (S:(f)
100-400) particles was greater during the high Mono than during the high CHO diet
based on the levels of apolipoprotein B (means +/- SEM): 31.4 +/- 7.4 versus 20.0
+/- 3.8 mg/L (P: < 0.025, paired t test). The following variables did not differ
during the diet periods: number of small VLDL (S:(f) 20-100) particles,
esterified cholesterol accumulated in THP-1 macrophages incubated with the same
number of big and small VLDL particles and particle composition. We conclude that
a high CHO diet might be preferable to a high Mono diet, on the basis of the
premise that more big VLDL particles could increase the atherosclerotic risk in
patients with diabetes.
PMID- 11015482
TI - Ingestion of protein hydrolysate and amino acid-carbohydrate mixtures increases
postexercise plasma insulin responses in men.
AB - To optimize the postexercise insulin response and to increase plasma amino acid
availability, we studied postexercise insulin levels after the ingestion of
carbohydrate and wheat protein hydrolysate with and without free leucine and
phenylalanine. After an overnight fast, eight male cyclists visited our
laboratory on five occasions, during which a control drink and two different
beverage compositions in two different doses were tested. After they performed a
glycogen-depletion protocol, subjects received a beverage (3.5 mL. kg(-1)) every
30 min to ensure an intake of 1.2 g. kg(-1). h(-1) carbohydrate and 0, 0.2 or 0.4
g. kg(-1). h(-1) protein hydrolysate (and amino acid) mixture. After the insulin
response was expressed as the area under the curve, only the ingestion of the
beverages containing wheat protein hydrolysate, leucine and phenylalanine
resulted in a marked increase in insulin response (+52 and + 107% for the 0.2 and
0.4 g. kg(-1). h(-1) mixtures, respectively; P: < 0. 05) compared with the
carbohydrate-only trial). A dose-related effect existed because doubling the dose
(0.2-0.4 g. kg(-1). h(-1)) led to an additional rise in insulin response (P: <
0.05). Plasma leucine, phenylalanine and tyrosine concentrations showed strong
correlations with the insulin response (P: < 0.0001). This study provides a
practical tool to markedly elevate insulin levels and plasma amino acid
availability through dietary manipulation, which may be of great value in
clinical nutrition, (recovery) sports drinks and metabolic research.
PMID- 11015483
TI - Geographic targeting of nutrition programs can substantially affect the severity
of stunting in Honduras.
AB - The effect of nutrition intervention programs in developing countries is likely
to vary with the degree to which the program can be successfully targeted at the
most vulnerable. In Honduras, the existence of a recent census of the height of
first-grade children makes it possible to assess a priori the effect of different
targeting strategies, holding constant other features of a hypothetical program.
We simulate a nutrition intervention with 20% national coverage and uniform gains
of 0.5 Z-scores for all beneficiaries, with a number of different approaches to
targeting. The VIIth National Census of First-Graders' Heights provides the
baseline scenario and permits identification of priority departments,
municipalities, schools and individuals, for a total of six alternative targeting
mechanisms. Effect is assessed on the basis of changes in the prevalence of
stunting (less than -2 Z-scores) and in two different measures of the severity of
stunting adapted from the economics literature (the malnutrition gap and the
quadratic malnutrition gap). We find that the simulated program has the potential
to substantially improve the severity, but not the prevalence of stunting in
Honduras. Household targeting with an imperfect indicator of vulnerability could
reduce the malnutrition gap by >20% and the quadratic malnutrition gap by >30%,
but would be very expensive to implement. "Broad stroke" geographic targeting
could reduce the same measures by 15 and 20%, respectively, and would be much
less expensive to implement. We conclude that geographic targeting has the
potential to substantially enhance the effect of nutrition programs on the
severity of stunting in Honduras.
PMID- 11015484
TI - Dietary vitamin A intake and nondietary factors are associated with reversal of
stunting in children.
AB - We examined prospectively the associations between dietary vitamin A intake,
nondietary factors and growth in 8174 Sudanese children ages 6-72 mo who were
stunted at the start of follow-up. All subjects were weighed and measured at
baseline and at 6-mo intervals for 18 mo of follow-up. Dietary vitamin A intake
during the prior 24 h was assessed using recall of vitamin A-containing foods at
baseline and 6-mo intervals. We examined the association of dietary vitamin A
intake with growth and the incidence of recovery of stunting after controlling
for age, sex, breast-feeding status and socioeconomic variables. We found that
carotenoid intake was associated with a greater incidence of reversal of
stunting. Children in the highest quintile grew 13 mm more during the study
period than children in the lowest quintile [95% confidence interval (CI): 0-25
mm] in multivariate analyses. The relative risk (RR) of recovery associated with
vitamin A intake was greater in infants up to 1 y old (RR = 3.3, CI: 0.9-11.7)
than in children > or =3 y of age (RR = 1.0, CI: 0.8-1. 3) (P:-value for
interaction = 0.08). Diets rich in carotenoids may increase the rate of recovery
from stunting in children. Dietary effects on growth might be strongest among
very young children and those who have been most malnourished. Age, sex, breast
feeding status, socioeconomic status and severity of baseline stunting also were
associated with reversal of stunting in this population.
PMID- 11015485
TI - Hookworms, malaria and vitamin A deficiency contribute to anemia and iron
deficiency among pregnant women in the plains of Nepal.
AB - Anemia and iron deficiency during pregnancy are prevalent in developing
countries, but their causes are not always known. We assessed the prevalence and
severity of anemia and iron deficiency and their association with helminths,
malaria and vitamin A deficiency in a community-based sample of 336 pregnant
women in the plains of Nepal. Hemoglobin, erythrocyte protoporphyrin (EP) and
serum ferritin were assessed in venous blood samples. Overall, 72.6% of women
were anemic (hemoglobin < 110 g/L), 19.9% had moderate to severe anemia
(hemoglobin < 90 g/L) and 80.6% had iron deficiency (EP > 70 micromol/mol heme or
serum ferritin < 10 microg/L). Eighty-eight percent of cases of anemia were
associated with iron deficiency. More than half of the women (54.2%) had a low
serum retinol concentration (<1.05 micromol/L), 74.2% were infected with
hookworms and 19.8% had Plasmodium vivax malaria parasitemia. Hemoglobin, EP and
serum ferritin concentrations were significantly worse and the prevalence of
anemia, elevated EP and low serum ferritin was increased with increasing
intensity of hookworm infection. Hookworm infection intensity was the strongest
predictor of iron status, especially of depleted iron stores. Low serum retinol
was most strongly associated with mild anemia, whereas P. vivax malaria and
hookworm infection intensity were stronger predictors of moderate to severe
anemia. These findings reinforce the need for programs to consider reducing the
prevalence of hookworm, malaria infection and vitamin A deficiency where
indicated, in addition to providing iron supplements to effectively control
anemia.
PMID- 11015487
TI - Soy protein peptides regulate cholesterol homeostasis in Hep G2 cells.
AB - The activation of LDL receptors was described recently in a human hepatoma cell
line (Hep G2) exposed both to alpha + alpha' subunits from 7S soy globulin and to
Croksoy(R)70, a commercial isoflavone-poor soy concentrate. To assess the final
identity of the peptide(s) putatively responsible for the biochemical effect,
experiments were performed in Hep G2 cells, exposed either to synthetic peptides
corresponding to specific sequences of 7S soy globulin or to peptides from the in
vitro digestion of Croksoy(R)70. Moreover, the ability of the whole 7S globulin,
its subunits and whole Croksoy(R)70 to interfere in the apolipoprotein B (apo B)
secretion in the medium as well as in sterol biosynthesis was evaluated in the
same model. Increased (125)I-LDL uptake and degradation vs. controls were shown
after Hep G2 incubation with a synthetic peptide (10(-)(4) mol/L, MW 2271 Da)
corresponding to positions 127-150 of the 7S globulin. Cells exposed to
Croksoy(R)70 enzyme digestion products showed a more marked up-regulation of LDL
receptors vs. controls, compared with vs. Hep G2 cells incubated with undigested
Croksoy(R)70. Among soy-derived products, only the 7S globulin inhibited apo B
secretion and (14)C-acetate incorporation when tested in Hep G2 cells at a
concentration of 1.0 g/L. These findings support the hypothesis that if one or
more peptides can reach the liver after intestinal digestion, they may elicit a
cholesterol-lowering effect. Moreover, the protein moiety, devoid of isoflavone
components, is likely to be responsible for this major biochemical effect of soy
protein.
PMID- 11015486
TI - Tomato intake in relation to mortality and morbidity among Sudanese children.
AB - The intake of foods that contain high levels of antioxidants may counteract the
adverse effects of oxidative stress and lead to improved immune function and
reduced risk of infectious disease. We prospectively examined the relationship
between the consumption of tomatoes, a rich source of antioxidants, and mortality
and diarrheal and respiratory morbidity rates among 28,753 children who were 6-60
mo old and enrolled in a longitudinal study in the Sudan. Children in each
household were visited every 6 mo for a maximum of four visits. At each round,
mothers recalled whether a child had consumed tomatoes in the previous 24 h.
Events (death or morbidity) reported at each round were prospectively allocated
according to the number of days of tomato intake. Intake of tomatoes for 2 or 3 d
compared with none was associated, respectively, with 48% (relative risk, 0. 53;
95% confidence interval, 0.30-0.91) and 83% (0.17; 0.04-0.72) reductions in
morality rates (P: for trend = 0.002). The association between tomato use and
death remained statistically significant (P: for trend = 0.004), even after
further adjustment for total vitamin A intake. Tomato intake was also associated
with a reduced risk of death associated with diarrhea in the week preceding death
(P: for trend = 0.009) or fever (P: for trend = 0.04). Intake of tomatoes was
also inversely and significantly associated with the risks of diarrheal and
respiratory infections. Our data suggest that tomatoes may be beneficial for
child health but also emphasize the general importance of food-based approaches
to the prevention of micronutrient malnutrition and protection of the health of
children in developing countries.
PMID- 11015488
TI - Incorporation and metabolism of dietary trans isomers of linolenic acid alter the
fatty acid profile of rat tissues.
AB - To study the influence on lipid metabolism and platelet aggregation of the fatty
acid isomerization that occurs during heat treatment, weanling rats were fed for
8 wk a diet enriched with 5% isomerized (experimental group) or normal (control
group) canola oil. Geometrical isomers of alpha-linolenic acid representing 0.2
g/100 g of the experimental diet were incorporated into liver, platelets, aorta
and heart, at the expense of their cis homologue and of 18:2(n-6). The major
isomer, 9c,12c,15t-18:3, was also metabolized to 5c,8c,11c,14c,17t-20:5 and to an
unknown compound, found in liver, platelets and aorta, which has been identified
tentatively as 7c, 10c,13c,16c,19t-22:5. The greater 20:4(n-6)/18:2(n-6) ratio in
the liver, platelets and heart of the experimental group than the control group
indicated an enhancement of desaturation activities. This induced a higher
content of long-chain (n-6) fatty acids in the experimental group. Platelet
aggregation tended to be slightly higher (P: = 0.065) in the experimental group.
We conclude that 0.2 g of trans isomers of alpha-linolenic acid per 100 g of diet
was sufficient to be incorporated and metabolized, thus altering the fatty acid
profile of rat tissues.
PMID- 11015489
TI - Riboflavin phosphorylation is the crucial event in riboflavin transport by
isolated rat enterocytes.
AB - In isolated rat enterocytes, both normoenergized (normal) and de-energized with
rotenone, riboflavin intracellular metabolic processes, operating in association
with a membrane-specific transport mechanism, were investigated. The contents of
unlabeled (endogenous) and labeled (exogenous) flavins [riboflavin (RF), flavin
mononucleotide (FMN), flavin adenindinucleotide (FAD)] were determined by HPLC
before and after incubation with tritiated RF. In normoenergized enterocytes,
total labeled RF content (i.e., total uptake, the sum of RF membrane transport
and intracellular metabolism) increased steadily to a plateau after 20 min
incubation; FMN and FAD contents reached a plateau between 3 and 20 min, whereas
free RF content increased constantly. The phosphorylated forms prevailed over the
free form ( approximately 60% of total flavins). In de-energized enterocytes, RF
total uptake was significantly lower than in normoenergized enterocytes and
reached a plateau after only 3 min incubation. FMN and FAD contents were
significantly lower than in normoenergized enterocytes, and free RF represented
the prevailing form of flavins (70% of total RF ). In both normoenergized and de
energized enterocytes, the contents of unlabeled total RF, FMN and FAD decreased
significantly after 20 min incubation, whereas free RF increased significantly
only in normoenergized enterocytes. After 20 min incubation, the RF structural
analog 8-dimethyl-amino-8-demethyl-RF caused a significant decrease of all flavin
contents, whereas 5'-deoxy-RF decreased only the total and free RF contents.
Results directly confirmed the leading role of metabolic processes such as
phosphorylation in RF transport by isolated small intestinal enterocytes.
PMID- 11015490
TI - The diurnal rhythm of energy expenditure differs between obese and glucose
intolerant rats and streptozotocin-induced diabetic rats.
AB - Otsuka Long Evans Tokushima Fatty (OLETF) rats were developed as a model of
noninsulin-dependent diabetes mellitus (NIDDM) with mild obesity. Changes in
carcass composition and in the daily profile of energy expenditure were examined
before and after manifestation of diabetes (8 and 24 wk, respectively), and
compared with the normal control Long Evans Tokushima (LETO) rats and
streptozotocin (STZ)-induced diabetic LETO rats. OLETF rats had greater body
weights than LETO rats and significantly greater absolute and relative fat
weights. A diurnal rhythm of energy expenditure associated with two peaks was
observed in LETO rats, but the two peaks were not apparent in OLETF rats at 24 wk
of age. A diurnal rhythm associated with one peak was observed in STZ-induced
diabetic LETO rats. Energy derived from fat constituted this peak; the pattern of
the daily energy expenditure was significantly different from that of either
nontreated LETO or OLETF rats at 24 wk of age. NIDDM in OLETF rats at 24 wk of
age has only a small role in modification of the diurnal rhythm of energy
expenditure, whereas STZ-induced diabetes significantly affected the rhythm.
PMID- 11015491
TI - Mammary lipogenic enzyme activity, trans fatty acids and conjugated linoleic
acids are altered in lactating dairy cows fed a milk fat-depressing diet.
AB - The objectives of the present study were to examine the effect of a milk fat
depressing (MFD) diet on: 1) the activity of mammary acetyl-CoA carboxylase (ACC)
and fatty acid synthase (FAS), 2) ACC mRNA relative abundance and 3)
distributions of conjugated linoleic acids (CLA) and trans-18:1 fatty acids (tFA)
in milk fat. Twelve lactating Holstein cows were used in a single reversal
design. Two diets were fed: a control diet (60:40% forage/concentrate) and an MFD
diet (25:70% forage/concentrate, supplemented with 5% soybean oil). The MFD diet
decreased (P: < 0 0.001) milk fat by 43% and ACC and FAS activity by 61 and 44%,
respectively. A reduced ACC mRNA relative abundance (P: < 0.001) corresponded
with the lower ACC activity. The fatty acids synthesized de novo were decreased
(P: < 0. 002), whereas tFA were increased from 1.9 to 15.6% due predominantly to
a change in trans-10-18:1 isomer (P: < 0.001). With the MFD diet, the trans-7,
cis-9 and trans-10, cis-12 CLA isomers were elevated (P: < 0.001), in contrast to
the decrease in trans-11-18:1 (P: < 0. 001) and cis-9, trans-11-18:2. The data
were consistent with a dietary effect on mammary de novo FA synthesis mediated
through a reduction in ACC and FAS activity and in ACC mRNA abundance. The
results were compatible with a role of trans-10, cis-12 CLA in milk fat
depression, but alterations noted in tFA and other CLA isomers suggest that they
also may be important during diet-induced milk fat depression.
PMID- 11015492
TI - Boron supplementation of a semipurified diet for weanling pigs improves feed
efficiency and bone strength characteristics and alters plasma lipid metabolites.
AB - Two experiments were conducted to determine effects of dietary boron (B) on
performance, plasma minerals and metabolites, and bone characteristics in young
pigs. In Experiment 1, 48 pigs (24 males, 24 females; 21 d old) were allotted to
pens, which were randomly assigned to one of the following dietary treatments: 1)
control (natural ingredient diet; 6.7 mg B/kg diet), 2) control + 5 mg B/kg diet
and 3) control + 15 mg B/kg diet. Boron was supplemented as sodium borate. In
Experiment 2, 48 pigs (24 males, 24 females; 21 d old) were assigned to the same
treatments described in Experiment 1; however, the basal diet was a semipurified
diet (0.98 mg B/kg diet). Diets were fed for 40 d; on d 40, blood samples were
obtained for determination of plasma mineral and metabolite concentrations.
Femurs were harvested from 8 pigs per treatment on d 40 for determination of
mechanical properties, ash and lipid percentage. In Experiment 1, B did not
affect performance, plasma minerals or metabolites or bone properties. In
Experiment 2, B supplementation improved (P: < 0.05) the gain:feed ratio and
increased plasma cholesterol and triglyceride concentrations. There was a
treatment x sex interaction (P: < 0.05) in Experiment 2 for bone lipid to be
lower and bending moment to be higher, with the response occurring in male pigs.
Other dependent variables in Experiment 2 were not affected by treatment. In
conclusion, B supplementation of a low B diet elicited responses of physiologic
importance to pigs. However, B supplementation of a natural ingredient diet did
not elicit a response.
PMID- 11015493
TI - Hypothalamic nuclei are malformed in weanling offspring of low protein
malnourished rat dams.
AB - Maternal low protein malnutrition during gestation and lactation (LP) is an
animal model frequently used for the investigation of long-term deleterious
consequences of perinatal growth retardation. Both perinatal malnutrition and
growth retardation at birth are risk factors for diabetic and cardiovascular
disturbances in later life. The pathophysiologic mechanisms responsible are
unknown. Hypothalamic nuclei are decisively involved in the central nervous
regulation of food intake, body weight and metabolism. We investigated effects of
a low protein diet (8% protein; control diet, 17% protein) during gestation and
lactation in rat dams on the organization of hypothalamic regulators of body
weight and metabolism in the offspring at weaning (d 20 of life). LP offspring
had significantly lower body weight than control offspring (CO; P: < 0.001),
associated with hypoglycemia and hypoinsulinemia (P: < 0. 005) on d 20 of life.
This was accompanied by a greater relative volume of the ventromedial
hypothalamic nucleus (P: < 0.01) and a greater numerical density of Nissl-stained
neurons in this nucleus (P: < 0.01) as well as in the paraventricular
hypothalamic nucleus (PVN; P: < 0.001). In contrast, no significant differences
in neuronal densities were observed generally in the lateral hypothalamic area,
arcuate hypothalamic nucleus (ARC), and dorsomedial hypothalamic nucleus between
LP offspring and CO offspring. On the other hand, LP offspring displayed fewer
neurons immunopositive for neuropeptide Y in the ARC (P: < 0.05), whereas in the
PVN, lower neuronal densities of neurons immunopositive for galanin were found in
LP offspring compared with CO offspring (P: < 0.001). On the contrary, in the
PVN, no significant group difference in the numerical density of cholecystokinin
8S-positive neurons was present. A long-term effect of these specific
hypothalamic alterations on body weight and metabolism in LP offspring during
later life is suggested.
PMID- 11015494
TI - Intake of soy products is associated with better plasma lipid profiles in the
Hong Kong Chinese population.
AB - We describe the pattern of soy intake and its association with blood lipid
concentrations in the Hong Kong Chinese population. Subjects were contacted by
random telephone survey and invited to a hospital for a physical examination and
blood tests. A total of 500 men and 510 women with an age range of 24-74 y
completed the dietary intake study. The dietary assessment was based on a
semiquantitative food frequency questionnaire that included 10 commonly consumed
soy items. Many (88%) of the study population had consumed some soy products
during the previous week. About 80% of the soy protein or isoflavones were
obtained from different forms of tofu, and an additional 9% was obtained from soy
milk. The mean weekly isoflavone intake was 102 +/- 107 mg in men and 77 +/- 90
mg in women. In men, soy intake and total plasma cholesterol were negatively
correlated (r = -0.09, P: = 0.04), as were soy intake and LDL cholesterol (r =
0.11, P: = 0.02). The respective values in women <50 y old were r = -0.11, P: =
0.04 and r = -0.11, P: = 0.05. Soy protein remained significantly associated with
these two lipid concentrations after adjustment for other social and dietary
confounders. Higher soy intake seemed to be related to a better plasma lipid
profile in men and in younger women, but more epidemiological studies and
controlled clinical trials in this setting would help to confirm the optimal
amount required for the prevention and treatment of hyperlipidemia.
PMID- 11015495
TI - Early weaning and prolonged nursing induce changes in cell proliferation in the
gastric epithelium of developing rats.
AB - Food deprivation stimulates cell proliferation in the gastric epithelium of
suckling, but not weanling rats. This study was designed to investigate the role
of diet on proliferation in developing animals, using early weaning and prolonged
nursing models. Rat pups were subjected to these dietary conditions at d 15 and
were killed 3 or 7 d afterwards. One day before killing, half of pups were
deprived of food. Body weights were recorded. After mitosis blockade, the
histologic sections of the stomach were used for the evaluation of cell
proliferation and methapasic cell distribution along the gland, and for the
measurement of mucosa thickness. Body weight was impaired at 18 d by early
weaning and at 22 d by prolonged nursing. Food restriction promoted a 10-15%
weight loss regardless of dietary conditions. At 18 d, food deprivation inhibited
cell division (P: < 0.01) and reduced the thickness of the mucosa (P: < 0.05) in
rats that were weaned early. At 22 d, only the thickness of the mucosa was
different between the groups that were subjected to early weaning and prolonged
nursing (P: < 0.05), regardless of feeding state. The frequency of dividing cells
along the gland was affected by early weaning in 18- and 22-d-old rats. These
results suggest the following: 1) food deprivation effects are dependent on
dietary condition at 18 d because different proliferative responses were achieved
after early weaning and prolonged nursing; 2) the lack of changes after dietary
manipulation in 22-d-old rats indicates a nonresponsive period during postnatal
development. We conclude that milk is a modulatory factor for cell proliferation
in the gastric mucosa of rats.
PMID- 11015496
TI - Fermentation by gut microbiota cultured in a simulator of the human intestinal
microbial ecosystem is improved by supplementing a soygerm powder.
AB - An in vitro model, designated the Simulator of the Human Intestinal Microbial
Ecosystem (SHIME), was used to study the effect of a soygerm powder rich in beta
glycosidic phytoestrogenic isoflavones on the fermentation pattern of the colon
microbiota and to determine to what extent the latter metabolize the conjugated
phytoestrogens. Initially, an inoculum prepared from human feces was introduced
into the reactor vessels and stabilized over 3 wk using a culture medium. This
stabilization period was followed by a 2-wk control period during which the
microbiota were monitored. The microbiota were then subjected to a 2-wk treatment
period by adding 2.5 g/d soygerm powder to the culture medium. The addition
resulted into an overall increase of bacterial marker populations
(Enterobacteriaceae:, coliforms, Lactobacillus: sp., Staphylococcus: sp. and
Clostridium: sp.), with a significant increase of the Lactobacillus: sp.
population. The short-chain fatty acid (SCFA) concentration increased
approximately 30% during the supplementation period; this was due mainly to a
significant increase of acetic and propionic acids. Gas analysis revealed that
the methane concentration increased significantly. Ammonium and sulfide
concentrations were not influenced by soygerm supplementation. Use of an
electronic nose apparatus indicated that odor concentrations decreased
significantly during the treatment period. The beta-glycosidic bonds of the
phytoestrogenic isoflavones were cleaved under the conditions prevailing in the
large intestine. The increased bacterial fermentation after addition of the
soygerm powder was paralleled by substantial metabolism of the free isoflavones
(genistein, daidzein and glycitein), resulting in recovery of only 12-17% of the
supplemented isoflavones.
PMID- 11015497
TI - Body weight-specific zinc compartmental masses in girls significantly exceed
those reported in adults: a stable isotope study using a kinetic model.
AB - Maintaining optimal zinc status is important for normal growth and development in
children, but minimal data are available regarding zinc metabolism in this age
group. Our objectives were to utilize stable isotope-based compartmental modeling
techniques to investigate zinc metabolism in healthy children; to expand a
current stable isotope-based model to include red blood cell data; and to compare
kinetic parameters in children with those previously reported in adults. Seven
healthy girls, age 9.94 +/- 0.79 y, received 1.1 mg of a (67)zinc-enriched tracer
orally and 0.5 mg of a (70)zinc-enriched tracer intravenously. Blood, urine and
fecal samples were collected for 6 d. Stable isotope enrichments were measured by
thermal ionization magnetic sector mass spectrometry. A six-compartment model
based on a model previously reported in adults was used; the model excluded red
blood cell data. Body weight-corrected masses of the body zinc compartments
derived using this model were significantly greater in children than those
reported in adults. Modification of the model to include a red blood cell
compartment increased the total identifiable zinc mass of the nongastrointestinal
compartments by approximately 2.5%. We conclude that compartmental modeling can
be used to describe zinc kinetics in children, and that the body weight-corrected
zinc pool masses are significantly greater in children than in adults.
PMID- 11015498
TI - Foodborne illnesses and nutritional status: a statement from an American Society
for Nutritional Sciences Working Group.
PMID- 11015499
TI - Use of bootstrap procedure and Monte Carlo simulation.
PMID- 11015500
TI - Response to use of bootstrap procedure and monte carlo simulation
PMID- 11015501
TI - Cerebral intravascular oxygenation correlates with mean arterial pressure in
critically ill premature infants.
AB - OBJECTIVES: Premature infants experience brain injury, ie, germinal matrix
intraventricular hemorrhage (GMH-IVH) and periventricular leukomalacia (PVL), in
considerable part because of disturbances in cerebral blood flow (CBF). Because
such infants are susceptible to major fluctuations in mean arterial blood
pressure (MAP), impaired cerebrovascular autoregulation would increase the
likelihood for the changes in CBF that could result in GMH-IVH and PVL. The
objectives of this study were to determine whether a state of impaired
cerebrovascular autoregulation could be identified reliably and conveniently at
the bedside, the frequency of any such impairment, and the relation of the
impairment to the subsequent occurrence of severe GMH-IVH and PVL. PATIENTS AND
METHODS: To monitor the cerebral circulation continuously and noninvasively, we
used near-infrared spectroscopy (NIRS) to determine quantitative changes in
cerebral concentrations of oxygenated hemoglobin (HbO(2)) and deoxygenated
hemoglobin (Hb) from the first hours of life. Our previous experimental study
showed a strong correlation between a measure of cerebral intravascular
oxygenation (HbD), ie, HbD = HbO(2) - Hb, determined by NIRS, and volemic CBF,
determined by radioactive microspheres. We studied 32 very low birth weight
premature infants (gestational age: 23-31 weeks; birth weight: 605-1870 g)
requiring mechanical ventilation, supplemental oxygen, and invasive blood
pressure monitoring by NIRS from 1 to 3 days of age. MAP measured by arterial
catheter pressure transducer and arterial oxygen saturation measured by pulse
oximetry were recorded simultaneously. The relationship of MAP to HbD was
quantitated by coherence analysis. RESULTS: Concordant changes (coherence scores
>. 5) in HbD and MAP, consistent with impaired cerebrovascular autoregulation,
were observed in 17 of the 32 infants (53%). Eight of the 17 infants (47%)
developed severe GMH-IVH or PVL or both. Of the 15 infants with apparently intact
autoregulation, ie, coherence scores <.5, only 2 (13%) developed severe
ultrasonographic lesions. Thus, for the entire study population of 32 infants, 8
of the 10 with severe lesions exhibited coherence scores >.5. CONCLUSIONS: We
conclude that NIRS can be used in a noninvasive manner at the bedside to identify
premature infants with impaired cerebrovascular autoregulation, that this
impairment is relatively common in such infants, and that the presence of this
impairment is associated with a high likelihood of occurrence of severe GMH
IVH/PVL.
PMID- 11015502
TI - Adverse sedation events in pediatrics: analysis of medications used for sedation.
AB - OBJECTIVES: To perform a systematic investigation of medications associated with
adverse sedation events in pediatric patients using critical incident analysis of
case reports. METHODS: One hundred eighteen case reports from the adverse drug
reporting system of the Food and Drug Administration, the US Pharmacopoeia, and
the results of a survey of pediatric specialists were used. Outcome measures were
death, permanent neurologic injury, prolonged hospitalization without injury, and
no harm. The overall results of the critical incident analysis are reported
elsewhere. The current investigation specifically examined the relationship
between outcome and medications: individual and classes of drugs, routes of
administration, drug combinations and interactions, medication errors and
overdoses, patterns of drug use, practitioners, and venues of sedation. RESULTS:
Ninety-five incidents fulfilled study criteria and all 4 reviewers agreed on
causation; 60 resulted in death or permanent neurologic injury. Review of adverse
sedation events indicated that there was no relationship between outcome and drug
class (opioids; benzodiazepines; barbiturates; sedatives; antihistamines; and
local, intravenous, or inhalation anesthetics) or route of administration (oral,
rectal, nasal, intramuscular, intravenous, local infiltration, and inhalation).
Negative outcomes (death and permanent neurologic injury) were often associated
with drug overdose (n = 28). Some drug overdoses were attributable to
prescription/transcription errors, although none of 39 overdoses in 34 patients
seemed to be a decimal point error. Negative outcomes were also associated with
drug combinations and interactions. The use of 3 or more sedating medications
compared with 1 or 2 medications was strongly associated with adverse outcomes
(18/20 vs 7/70). Nitrous oxide in combination with any other class of sedating
medication was frequently associated with adverse outcomes (9/10). Dental
specialists had the greatest frequency of negative outcomes associated with the
use of 3 or more sedating medications. Adverse events occurred despite drugs
being administered within acceptable dosing limits. Negative outcomes were also
associated with drugs administered by nonmedically trained personnel and drugs
administered at home. Some injuries occurred on the way to a facility after
administration of sedatives at home; some took place in automobiles or at home
after discharge from medical supervision. Deaths and injuries after discharge
from medical supervision were associated with the use of medications with long
half-lives (chloral hydrate, pentobarbital, promazine, promethazine, and
chlorpromazine). CONCLUSIONS: Adverse sedation events were frequently associated
with drug overdoses and drug interactions, particularly when 3 or more drugs were
used. Adverse outcome was associated with all routes of drug administration and
all classes of medication, even those (such as chloral hydrate) thought to have
minimal effect on respiration. Patients receiving medications with long plasma
half-lives may benefit from a prolonged period of postsedation observation.
Adverse events occurred when sedative medications were administered outside the
safety net of medical supervision. Uniform monitoring and training standards
should be instituted regardless of the subspecialty or venue of practice.
Standards of care, scope of practice, resource management, and reimbursement for
sedation should be based on the depth of sedation achieved (ie, the degree of
vigilance and resuscitation skills required) rather than on the drug class, route
of drug administration, practitioner, or venue.
PMID- 11015504
TI - Neonatal outcome of preimplantation genetic diagnosis by polar body removal: the
first 109 infants.
AB - CONTEXT: Our center developed the technique of preimplantation genetic diagnosis
(PGD) by sequential polar body removal (PBR) for the diagnosis of Mendelian
disorders and aneuploidies. This study examines the obstetric and neonatal
outcome of the first 109 live births after PGD by PBR. OBJECTIVE: To determine if
there were any observable effects of PGD by PBR on perinatal morbidity and
mortality, birth defects, and growth parameters. DESIGN: Data on perinatal
outcome were gathered for the first 109 infants by parental reporting and
confirmed by telephone interview and chart review when indicated. In infants >6
months old, a follow-up telephone interview was performed establishing the
developmental milestones attained by the child. SETTING: A research center
conducting an institutional review board-approved research protocol in PGD.
PATIENTS: All patients who had PGD by PBR who had clinical pregnancies. MAIN
OUTCOME MEASURES: Gestational age, mode of delivery, perinatal mortality, birth
weight, birth length, the presence of birth defects, and developmental
milestones. RESULTS: There was no significant decrease in birth length or weight,
or the frequency of small for gestational age infants. No specific pattern of
birth defects was observed. CONCLUSION: Thus far, there are no observable
detrimental effects of PGD by PBR on children born after the procedure.
PMID- 11015503
TI - The prevalence of genital human papillomavirus infections in abused and nonabused
preadolescent girls.
AB - OBJECTIVE: To compare the prevalence of genital human papillomavirus (HPV)
infections in sexually abused and nonabused preadolescent girls and assess the
feasibility of conducting a longitudinal study of the natural history of HPV
infection in this population. METHOD: Consecutively referred, 5- to 12-year-old
girls who were evaluated for sexual abuse by a Child Advocacy and Protection Team
were invited to participate in the study. During a standard forensic medical
examination, 2 specimens for HPV testing were obtained (one by rubbing a Dacron
swab over the perineum and the other by lavaging the vagina with phosphate
buffered saline). The specimens were evaluated for HPV DNA by polymerase chain
reaction using MY09/11 consensus primers and high-risk
(16,18,31,33,35,39,45,51,52, 56,58) and low-risk (6,11,42,43,44) types were
detected with a solution hybridization assay, the SHARP Signal System (Digene
Diagnostics). The genital area was examined for warts and subclinical,
colposcopic evidence of HPV. Participants were invited to return for longitudinal
evaluation at 4-month intervals for 2 years. RESULTS: Sexual abuse was confirmed
in 29 (72.5%) of the 40 study participants, suspected in 2 (5%), and ruled out in
9 (22.5%). None of the girls had genital warts or abnormal colposcopic findings.
HPV DNA was detected in 5 (16%) of the 31 girls with confirmed or suspected
sexual abuse (1 with high-risk and 4 with low-risk types) and none of the
nonabused girls (Fisher's exact test). Girls who tested positive and negative for
HPV did not differ significantly in age or type of abuse. Despite close telephone
follow-up and numerous attempts to schedule appointments, none of the
participants returned for follow-up. CONCLUSIONS: Genital HPV infection is more
common among sexually abused than nonsexually abused girls, with the majority of
infections not clinically apparent. Because it is so difficult to study the
natural history of these infections in abused children, it may be necessary to
draw inferences about the long-term sequelae of pediatric HPV infections from
longitudinal studies of girls who voluntarily initiate sexual activity soon after
menarche.
PMID- 11015505
TI - Video recording as a means of evaluating neonatal resuscitation performance.
AB - OBJECTIVE: To determine the compliance to Neonatal Resuscitation Program (NRP)
guidelines in our institution, by the use of videotaped newborn resuscitations.
BACKGROUND: NRP is the standard of care for newborn resuscitation. The
application of NRP guidelines and resuscitation skills in actual clinical
settings is undocumented. DESIGN/METHODS: A video recorder, mounted to the
radiant warmer in the main obstetrical operating room, was used to record all
high-risk resuscitations. All members of the resuscitation team were NRP
certified. The videotapes were reviewed within 14 days of the resuscitation and
then erased. This ongoing review was approved as a quality assurance (QA) project
ensuring confidentiality under California law. The first 100 resuscitations were
evaluated to assess NRP compliance. Each step in the resuscitation (positioning,
oxygen delivery, ventilation, chest compressions, intubation, and medication) was
graded. A score was devised, with 2 points being awarded for every correct
decision and proper procedure, 1 point for delayed interventions or inadequate
technique, and zero points for indicated procedures that were omitted or for
interventions that were not indicated. The total points were divided by the total
possible points for that patient. The scores for the first 25 resuscitations
(group 1) and the last 25 resuscitations (group 2) were compared. RESULTS: Fifty
four percent of the 100 resuscitations had deviations from the NRP guidelines.
Ten percent received overly aggressive stimulation and 22% had poor suction
technique. Of the 78 infants given oxygen, this decision was considered incorrect
in 15% and the delivery technique was poor in 10% of the infants given oxygen. Of
those requiring mask ventilation (n = 18), 24% had poor chest expansion, 11% used
an incorrect rate, and 17% had inadequate reevaluation. Twelve infants were
intubated; only 7 were successfully intubated on the first attempt and only 4
were intubated in <20 seconds. The longest intubation attempt was 50 seconds.
Naloxone was given to 2 patients. One was breathing spontaneously with a heart
rate >100. Resuscitations receiving a perfect evaluation score were more likely
to occur in infants needing less intervention. The level of resuscitation
required for groups 1 and 2 were statistically similar. There was no difference
in resuscitation scores between the 2 groups. Only the inappropriate use of deep
suctioning improved, with 8 of 25 events in group 1, and 0 of 25 in group 2.
CONCLUSIONS: We have found a significant number of deviations from the NRP
guidelines. Video recording of actual clinical practice is a useful QA tool for
monitoring the conduct of newborn resuscitation. We are now conducting repeat
video assessments of individual NRP providers to determine whether there is
improved performance.
PMID- 11015506
TI - The EPICure study: outcomes to discharge from hospital for infants born at the
threshold of viability.
AB - OBJECTIVE: To evaluate the outcome for all infants born before 26 weeks of
gestation in the United Kingdom and the Republic of Ireland. This report is of
survival and complications up until discharge from hospital. METHODOLOGY: A
prospective observational study of all births between March 1, 1995 and December
31, 1995 from 20 to 25 weeks of gestation. RESULTS: A total of 4004 births were
recorded, and 811 infants were admitted for intensive care. Overall survival was
39% (n = 314). Male sex, no reported chorioamnionitis, no antenatal steroids,
persistent bradycardia at 5 minutes, hypothermia, and high Clinical Risk Index
for Babies (CRIB) score were all independently associated with death. Of the
survivors, 17% had parenchymal cysts and/or hydrocephalus, 14% received treatment
for retinopathy of prematurity (ROP), and 51% needed supplementary oxygen at the
expected date of delivery. Failure to administer antenatal steroids and postnatal
transfer for intensive care within 24 hours of birth were predictive of major
scan abnormality; lower gestation was predictive of severe ROP, while being born
to a black mother was protective. Being of lower gestation, male sex, tocolysis,
low maternal age, neonatal hypothermia, a high CRIB score, and surfactant therapy
were all predictive of oxygen dependency. Intensive care was provided in 137
units, only 8 of which had >5 survivors. There was no difference in survival
between institutions when divided into quintiles based on their numbers of
extremely preterm births or admissions. CONCLUSIONS: This study provides outcome
data for this geographically defined cohort; survival and neonatal morbidity are
consistent with previous data from the United Kingdom and facilitate comparison
with other geographically based data.
PMID- 11015507
TI - Costs and effectiveness of ultrasonography and limited computed tomography for
diagnosing appendicitis in children.
AB - BACKGROUND: A protocol of ultrasonography (US) followed by computed tomography
with rectal contrast (CTRC) has been shown to be 94% accurate in the diagnosis of
acute appendicitis in children. OBJECTIVE: To evaluate the changes in patient
management and costs of a protocol using US and CTRC in the evaluation of
appendicitis in children. DESIGN, SETTING, AND SUBJECTS: Prospective cohort study
of 139 children between 3 and 21 years of age who had equivocal clinical findings
for acute appendicitis seen in the emergency department of a large, urban
pediatric teaching hospital between July 1998 and December 1998. PROTOCOL:
Children with equivocal clinical presentations for acute appendicitis were
prospectively evaluated with US. Patients with positive findings for acute
appendicitis went directly to the operating room. Patients with negative or
equivocal findings on US underwent CTRC. Surgical management plans were recorded
before imaging, after US, and after CTRC. MAIN OUTCOME MEASURES: Surgical
management plans before and after the imaging protocol as well as total hospital
direct and indirect costs incurred or saved by each change in management were
determined. Costs were obtained through the hospital's cost database and by
ratios of costs to charges. RESULTS: Of the 139 children, the protocol resulted
in a beneficial change in management in 86 children (61.9%), no change in
management in 50 children (36.0%) and an incorrect change in management in 3
children (2.1%). US alone resulted in a beneficial change in management decision
in 12/31 children (38.7%), while US followed by CTRC resulted in a beneficial
change in management in 74/108 children (68.5%). The protocol resulted in a total
cost savings of $78 503.99 or $565/patient. CONCLUSION: A protocol of US followed
by CTRC in children with negative or equivocal US examinations results in a high
rate of beneficial change in management as well as in total cost savings in
children with equivocal clinical presentations for suspected appendicitis.
PMID- 11015508
TI - Decline in prevalence of neural tube defects in a high-risk region of the United
States.
AB - OBJECTIVES: To conduct surveillance for neural tube defects (NTDs) in a high-risk
region of the United States and to prevent occurrence and recurrence of NTDs
through the periconceptional use of folic acid supplements. DESIGN: Active and
passive methods were used for surveillance of NTD-affected pregnancies and births
during a 6-year period (October 1992-September 1998). Individual genetic
counseling was used to prevent NTD recurrences and a public awareness campaign
was used to reduce NTD occurrences. SETTING: State of South Carolina. PATIENTS:
All cases of spina bifida, anencephaly, and encephalocele identified among 278
122 live births and fetal deaths to South Carolina residents during 1992-1998
were included. MAIN OUTCOME MEASURE: Changes in occurrence and recurrence rates
during a 6-year period. RESULTS: Over the 6 years of surveillance, the prevalence
rates for NTDs decreased from 1.89 to.95 cases per 1000 live births and fetal
deaths. The prevalence decrease is explained primarily by a decrease in cases of
spina bifida. Isolated NTDs accounted for 297/360 (82%) NTDs and 63/360 (18%) had
at least 1 other structural anomaly. Females predominated among isolated NTDs but
the sex distribution was equal among NTD cases with other anomalies. Prevalence
rates for whites (1.48 cases per 1000 live births and fetal deaths) were higher
than rates for blacks (.87 cases per 1000 live births and fetal deaths). There
were no NTD recurrences in 113 subsequent pregnancies to mothers of infants with
isolated NTDs who took periconceptional folic acid. The rate of periconceptional
folic acid use among women of childbearing years increased from 8% to 35% during
the 6-year project period. CONCLUSION: The prevalence of NTDs in a high-risk
region has declined coincident with the increased periconceptional use of folic
acid supplements among women of childbearing age.neural tube defects, high-risk
region, birth defects, folic acid, spina bifida, anencephaly, encephalocele.
PMID- 11015509
TI - Pilot study of treatment with whole body hypothermia for neonatal encephalopathy.
AB - BACKGROUND: There is extensive experimental evidence to support the investigation
of treatment with mild hypothermia after birth asphyxia. However, clinical
studies have been delayed by the difficulty in predicting long-term outcome very
soon after birth and by concern about adverse effects of hypothermia. OBJECTIVES:
The objectives of this study were to determine whether it is feasible to select
infants with a bad neurological prognosis and to begin hypothermic therapy within
6 hours of birth, and to observe the effect of this therapy on relevant
physiologic variables. METHODS: Sixteen newborn infants with clinical features of
birth asphyxia (median cord blood pH: 6.74; range: 6.58-7.08) were assessed by
amplitude integrated electroencephalography (aEEG), and mild whole body
hypothermia was instituted within 6 hours of birth in the 10 infants with an aEEG
prognostic of a bad outcome. Rectal temperature was maintained at 33.2 +/-
(standard deviation).6 degrees C for 48 hours. Rectal and tympanic membrane
temperature, blood pressure, heart rate, blood gases, blood lactate, full blood
count, blood electrolytes, high and low shear rate viscosity, and coagulation
studies were monitored during and after cooling. A preliminary assessment of
neurological outcome was made by repeated magnetic resonance imaging (MRI) and
neurological examination. RESULTS: All infants selected to receive hypothermia
developed convulsions and a severe encephalopathy. During 48 hours of hypothermia
infants had prolonged metabolic acidosis (median pH: 7.30; base excess: -6.3 mmol
x L(-1), a high blood lactate (median lactate: 5.3 mmol x L(-1)) and low blood
potassium levels (median value: 3.9 mmol x L(-1)) x Hypothermia was associated
with lower heart rate and higher mean blood pressure. However, these changes did
not seem to be clinically relevant and no significant complication of hypothermia
was encountered. Blood viscosity and coagulation studies were similar during and
after cooling. Unusual MRI findings were noted in 3 infants: transverse sinus
thrombosis with subsequent small cerebellar infarct; probable thrombosis in the
straight sinus; and hemorrhagic cerebral infarction. Six of the 10 cooled infants
had minor abnormalities only or normal follow-up neurological examination; 3
infants died and 1 had major abnormalities. None of the 6 infants with a normal
aEEG developed severe neonatal encephalopathy or neurological sequel.
CONCLUSIONS: After birth asphyxia infants can be objectively selected by aEEG and
hypothermia started within 6 hours of birth in infants at high risk of developing
severe neonatal encephalopathy. Prolonged mild hypothermia to 33 degrees C to 34
degrees C is associated with minor physiologic abnormalities. Further studies of
both the safety and efficacy of mild hypothermia, including further neuroimaging
studies, are warranted.
PMID- 11015510
TI - Pneumococcal mastoiditis in children.
AB - OBJECTIVE: To determine the impact of antibiotic resistance on the frequency,
clinical features, and management/outcome of mastoiditis attributable to
Streptococcus pneumoniae. DESIGN: Retrospective review of the medical records of
children with mastoiditis caused by S pneumoniae from September 1993 through
December 1998. PATIENTS: Infants and children with pneumococcal mastoiditis cared
for at 8 children's hospitals in the United States. RESULTS: Thirty-four children
with pneumococcal mastoiditis were identified. The median age of the children was
12 months (range: 2 months-12.5 years); 28 (82%) were =2 years old. Six
children had recurrent otitis media. A subperiosteal abscess was noted in 13
children (37%). The mastoids were abnormal in all 25 patients on whom computed
tomography was performed. There was no trend toward increasing numbers of cases
per year despite increasing proportions of pneumococcal isolates, which were
nonsusceptible to penicillin. Serogroup 19 accounted for 57% of isolates,
serogroup 23 for 14.3% of isolates, and serotype 3 for 10. 7% of isolates. Except
for receipt of less antibiotic therapy in the previous 30 days, children with
penicillin-susceptible isolates had similar demographic features and clinical
findings and surgical treatment as did children whose isolates were
nonsusceptible to penicillin. CONCLUSIONS: Pneumococcal mastoiditis occurs
primarily in children <2 years of age and usually is not associated with a
history of recurrent otitis media. The number of cases of mastoiditis caused by S
pneumoniae occurring among 8 children's hospitals has remained stable despite
increasing rates of antibiotic-resistant S pneumoniae. Serogroup 19 is the
leading serogroup associated with pneumococcal mastoiditis. Streptococcus
pneumoniae, mastoiditis, serotypes, resistance.
PMID- 11015511
TI - Prospective randomized trial of early versus late enteral iron supplementation in
infants with a birth weight of less than 1301 grams.
AB - OBJECTIVES: To examine whether early enteral iron supplementation (EI) would
improve serum ferritin as a measure of nutritional iron status at 2 months of age
and would prevent definite iron deficiency (ID) in infants with a birth weight of
<1301 g. METHODS: Infants were randomly assigned to receive enteral iron
supplementation of 2 to 6 mg/kg/day as soon as enteral feedings of >100 mL/kg/day
were tolerated (EI) or at 61 days of life (late enteral iron supplementation
[LI]). Nutritional iron status was assessed: 1) at birth, 2) at 61 days of life,
3) when the infants reached a weight of 1.6 times birth weight, and 4) before
blood was transfused at a hematocrit of <.25. ID was defined by any one of the
following criteria: ferritin, <12 microg/L; transferrin saturation, <17%; or
increase of absolute reticulocyte counts by >50% one week after the onset of
enteral iron supplementation. Restrictive red cell transfusion guidelines were
followed and all transfusions were documented. Erythropoietin was not
administered. The primary outcome variables were: 1) ferritin at 61 days and 2)
the number of infants with ID. RESULTS: Ferritin at 61 days was not different
between the groups. Infants in the LI group were more often iron-deficient (26/65
vs 10/68) and received more blood transfusions after day 14 of life. No adverse
effects of EI were noted. CONCLUSIONS: EI is feasible and probably safe in
infants with birth weight <1301 g. EI may reduce the incidence of ID and the
number of late blood transfusions. ID may occur in very low birth weight infants
despite early supplementation with iron and should be considered in the case of
progressive anemia.preterm infant, iron supplementation, iron deficiency, blood
transfusion.
PMID- 11015512
TI - Venous and arterial hematologic profiles of very low birth weight infants.
European Multicenter rhEPO Study Group.
AB - OBJECTIVE: In very low birth weight (VLBW) infants, diagnostic and therapeutic
decisions depend on hematologic values. As few data are available, we studied the
course during the first 6 weeks of life. DESIGN: Four prospective longitudinal
cohort studies were retrospectively combined assessing hematologic profiles of
562 VLBW infants. For characterization of red blood cells and iron, infants
receiving erythropoietin were excluded. For characterization of white blood cells
and platelets, infants receiving antibiotics were excluded. RESULTS: The third
(3rd)/median/97th percentiles on day 3 were as follows: hemoglobin:
11.0/15.6/19.8 g/dL; hematocrit: 35/47/60%; red blood cells: 3.2/4.2/5.3 x
10(12)/L; reticulocytes:. 6/7.1/27.8%; platelets: 58/203/430 x 10(9)/L; white
blood cells: 3. 6/9.5/38.3 x 10(9)/L; neutrophils:.7/4.7/25.3 x 10(9)/L;
ferritin: 27/140/504 ng/mL; iron:.8/7.5/26.7 micromol/L; transferrin saturation:
2.6/22.7/79.8%. Transferrin saturation was <24% in 51%, ferritin concentration
<100 ng/mL in 32%, and platelets <150 x 10(9)/L in 29% of this population. The
steady decrease of red cell parameters was mitigated by transfusions. Neutrophils
decreased steadily, and were <1.75 x 10(9)/L in 35% at 6 weeks. CONCLUSIONS: Iron
indices and platelet counts on day 3 and neutrophil counts at 2 to 6 weeks of age
are lower than previously assumed in VLBW infants and lower than in larger
prematures.
PMID- 11015513
TI - When to suspect fungal infection in neonates: A clinical comparison of Candida
albicans and Candida parapsilosis fungemia with coagulase-negative staphylococcal
bacteremia.
AB - OBJECTIVES: To determine the epidemiology of candidemia in our neonatal intensive
care unit; to compare risk factors, clinical presentation, and outcomes for
neonates infected with Candida albicans, Candida parapsilosis, and coagulase
negative staphylococcus (CoNS); and to suggest a rational approach to empiric
antifungal therapy of neonates at risk for nosocomial infection. DESIGN:
Retrospective chart review of all neonatal intensive care unit patients with
systemic candidiasis or CoNS infection between January 1, 1995 and July 31, 1998
at Duke University Medical Center. RESULTS: Fifty-one patients were reviewed.
Nine of 19 patients infected with C parapsilosis and 5 of 15 patients infected
with C albicans died of fungemia. Seventeen neonates had >2 positive cultures for
CoNS obtained within 96 hours and 1 died. There was no statistically significant
difference in birth weight, gestational age, or age at diagnosis between patient
groups; however, candidemic patients had a sevenfold higher mortality rate.
Before diagnosis, candidemic patients had greater exposure to systemic steroids,
antibiotics, and catecholamine infusions. Of the 51 patients, 32 received third
generation cephalosporins in the 2 weeks before diagnosis and 19 did not. Twenty
nine of the 32 who were treated with third-generation cephalosporins subsequently
developed candidemia, while candidemia occurred in only 5 of 19 patients who were
not treated with cephalosporins. At the time of diagnosis, candidemic patients
were more likely to have required mechanical ventilation and were less likely to
be tolerating enteral feeding. Multivariate clustered logistic regression
analysis revealed that candidemic patients had more exposure to third-generation
cephalosporins. Once the clinician was notified of a positive blood culture for
Candida, patients infected with C parapsilosis retained their central catheters
longer than patients infected with C albicans. CONCLUSIONS: In this retrospective
review, we were able to identify aspects of the clinical presentation and
medication history that may be helpful in differentiating between candidemia and
CoNS bacteremia. Those key features may be used by clinicians to initiate empiric
amphotericin B therapy in premature neonates at risk for nosocomial infections.
Prolonged use of third-generation cephalosporins was strongly associated with
candidemia. There was no statistically significant difference in the morbidity
and mortality between patients infected with C parapsilosis and those infected
with C albicans. Observed delays in removal of the central venous catheter may
have contributed to finding a mortality rate from C parapsilosis that was higher
than was previously reported.
PMID- 11015514
TI - Different beta-casein fractions in Icelandic versus Scandinavian cow's milk may
influence diabetogenicity of cow's milk in infancy and explain low incidence of
insulin-dependent diabetes mellitus in Iceland.
AB - OBJECTIVES: To compare children with insulin-dependent diabetes mellitus (IDDM)
with controls in Iceland regarding their consumption of cow's milk in infancy,
and to investigate the beta-casein fractions in Scandinavian and Icelandic cow's
milk. The A1 variant of beta-casein has been shown to be diabetogenic in animal
studies, and suggestions have been made that the B variant of beta-casein acts
similarly. Differences in the relative proportions of beta-casein fractions might
explain the lower incidence of IDDM in Iceland than in Scandinavia. METHODS: A
retrospective case-control study on IDDM patients and matching controls was
performed in Iceland to compare their diets in infancy. Fifty-five children with
IDDM born in Iceland over a 16-year period and randomly collected controls (n =
165) were recruited to the study. Mothers of the children answered questions on
breastfeeding habits and on when cow's milk products were introduced. Samples of
cow's milk from randomly selected milk batches from the largest consumption areas
in Iceland and Scandinavia were collected. The milk samples were freeze-dried and
their beta-casein fractions were analyzed using capillary electrophoresis.
RESULTS: No significant difference was found between IDDM patients and controls
in the frequency and duration of breastfeeding or the first introduction of cow's
milk products. The analyses of milk samples showed that the percentage of the A1
and B variants of beta-casein in Icelandic milk was significantly lower than in
the milk from the Scandinavian countries. CONCLUSIONS: Cow's milk consumption in
infancy is not related to IDDM in Iceland. The lower fraction of A1 and B beta
caseins in Icelandic cow's milk may explain why there is a lower incidence of
IDDM in Iceland than in Scandinavia.
PMID- 11015515
TI - Otitis media in childhood in relation to preschool language and school readiness
skills among black children.
AB - OBJECTIVE: To examine whether otitis media with effusion (OME) and associated
hearing loss (HL) during the first 5 years of life were related to children's
language skills during the preschool years and to school readiness skills at
entry to kindergarten. METHODS: In a prospective study, the ears of 85 black
children primarily from low-income families and recruited from community-based
childcare programs were repeatedly examined from 6 months to 5 years of age for
the presence of OME and from 6 months to 4 years of age for HL when well and ill
with OME. Assessments were made annually of the children's child-rearing
environments at home and in childcare, and children's language skills between 3
and 5 years of age and readiness skills in literacy and math were evaluated at
entry into kindergarten. RESULTS: Children had either bilateral or unilateral OME
approximately 30.4% and HL 19.6% of the observation time. OME and associated HL
were significantly positively correlated with some measures of expressive
language at 3 and 4 years of age; however, these direct relationships were no
longer significant when the child's gender, socioeconomic status, maternal
educational level, and the responsiveness and support of the home and childcare
environments were also considered. Further, both OME and HL were moderately
correlated with school readiness skills at entry to school, with children having
more OME scoring lower in verbal math problems and with children with more HL
scoring lower in math and recognizing incomplete words. These associations
continued to remain significant even after partialing out the child and family
background factors. CONCLUSIONS: There was not a significant relationship between
children's early OME history or HL and language skills during the preschool
years. However, children with more frequent OME had lower scores on school
readiness measures. These associations were moderate in degree, however, and the
home environment was more strongly related to academic outcomes than was OME or
HL. These results should be interpreted cautiously when generalizing to other
populations.
PMID- 11015516
TI - Large congenital melanocytic nevi and the risk for development of malignant
melanoma and neurocutaneous melanocytosis.
AB - OBJECTIVE: To determine the risk for developing malignant melanoma and
neurocutaneous melanocytosis (NCM) in patients with large congenital melanocytic
nevi. DESIGN: Follow-up data suitable for calculations were available on 160
patients in the New York University Registry of Large Congenital Melanocytic Nevi
who had been free of known melanomas or NCM when entered into the Registry. The
cumulative 5-year life-table risks for developing melanoma and NCM were
calculated. The relative risk for developing melanoma, using a control general
population reference group, was determined. RESULTS: The 160 patients (median age
at entry: 14 months) were followed prospectively for an average of 5.5 years.
Three extracutaneous melanomas developed: 2 were in the central nervous system
(CNS) and 1 was retroperitoneal. The 5-year cumulative life-table risk for
developing melanoma was 2.3% (95% confidence interval [CI]:.8-6.6) and the
relative risk was 101 (95% CI: 21-296). No melanoma occurred within a large
congenital melanocytic nevus. Four patients developed manifest NCM, 2 with CNS
melanomas. The 5-year cumulative life-table risk for developing NCM was 2.5% (95%
CI:.8-7.2). Ten patients were excluded from the calculations because of
preexisting disease on entry into the Registry: 5 with manifest NCM and 5 with
melanomas (3 in large congenital melanocytic nevi, 1 in nonnevus skin, and 1
unknown primary). CONCLUSIONS: Patients with large congenital melanocytic nevi
are at increased risk for developing melanomas. There is also a significant
increased risk for developing NCM. The high incidence of CNS involvement may
influence decisions concerning treatment of the large congenital melanocytic
nevi.
PMID- 11015517
TI - Prospective evaluation of propofol anesthesia in the pediatric intensive care
unit for elective oncology procedures in ambulatory and hospitalized children.
AB - OBJECTIVES: To evaluate our experience with propofol anesthesia delivered by
pediatric intensivists in the pediatric intensive care unit (PICU) to facilitate
elective oncology procedures in children performed by pediatric oncologists.
METHODS: Elective oncology procedures performed with propofol anesthesia in our
multidisciplinary, university-affiliated PICU were prospectively evaluated over a
7-month period. Ambulatory and hospitalized children were prescheduled for their
procedure, underwent a medical evaluation, and met fasting requirements before
the start of anesthesia. Continuous cardiorespiratory and neurologic monitoring
was performed by a pediatric intensivist and a PICU nurse, while the procedure
was performed by a pediatric oncologist. Propofol was delivered in intermittent
boluses to achieve the desired level of anesthesia. Information studied included
patient demographics, procedures performed, induction and total doses of propofol
used, the duration of the different phases of the patient's PICU stay, the
occurrence of side effects, the need for therapeutic interventions, and the
incidence of recall of the procedure. RESULTS: Fifty procedures in 28 children
(mean age: 7.5 +/- 4.3 years) were evaluated. Sixty-one percent of patients had
established diagnoses. Fifty-four percent of procedures were lumbar puncture with
intrathecal chemotherapy administration and 26% of procedures were bone marrow
aspirations with biopsy. Induction propofol doses were 2. 0 +/-.8 mg/kg for
ambulatory and hospitalized patients, while total propofol doses were 6.6 +/- 2.3
mg/kg and 7.9 +/- 2.4 mg/kg for ambulatory and hospitalized patients,
respectively. Induction time was 1.5 +/-.7 minutes, recovery time was 23.4 +/-
11.5 minutes, and total PICU time was 88.8 +/- 27.7 minutes. Transient decreases
in systolic blood pressure less than the fifth percentile for age occurred in 64%
of procedures, with a mean decrease of 25% +/- 10%. Intravenous fluids were
administered in 31% of these cases. Hypotension was more common in ambulatory
patients but was not predicted by propofol dose, anesthesia time, or age. Partial
airway obstruction was noted in 12% of procedures while apnea requiring bag-valve
mask ventilation occurred in 2% of procedures. Neither was associated with age,
propofol dose, or the duration of anesthesia. All procedures were successfully
completed and there were no incidences of recall of the procedure. CONCLUSIONS:
Propofol anesthesia is effective in achieving patient comfort and amnesia, while
optimizing conditions for elective oncology procedures in children. Although
transient hypotension and respiratory depression may occur, propofol anesthesia
seems to be safe to use for these procedures in the PICU setting. Recovery from
anesthesia was rapid and total stay was brief. Under the proper conditions,
propofol anesthesia delivered by pediatric intensivists in the PICU is a
reasonable option available to facilitate invasive oncology procedures in
children.
PMID- 11015518
TI - Depressive symptoms and cigarette smoking among teens.
AB - CONTEXT: Although several risk factors for tobacco use have been implicated in
the development of depression, smoking progression has typically been viewed as a
consequence of depression. The results of limited longitudinal studies are
controversial. OBJECTIVE: To assess the nature and direction of the relationship
between cigarette smoking and depression among teens. DESIGN: Prospective
analysis of baseline and 1-year follow-up data from the National Longitudinal
Study of Adolescent Health. SETTING: In-home teen and parent interviews.
PARTICIPANTS: Two samples were identified. For the first sample, 8704 adolescents
who were not depressed at baseline based on CES-D scores were identified for
analyses of the effects of cigarette smoking on development of high depressive
symptomatology. Baseline smoking status, which could vary in this group, was the
predictor of interest in these analyses. For the second sample, 6947 teens who
had not smoked cigarettes in the 30 days before the baseline survey (noncurrent
smokers) were identified for analyses on the effect of high depressive symptoms
on subsequent moderate to heavy cigarette use at 1 year of follow-up. Baseline
high depressive symptomatology based on CES-D score was the predictor of interest
in this sample. MAIN OUTCOME MEASURES: Among the nondepressed, developing high
depressive symptoms at 1 year of follow-up. Among noncurrent smokers, smoking at
least 1 pack per week at 1 year of follow-up. RESULTS: For the nondepressed,
multivariate modeling revealed that current cigarette smoking was the strongest
predictor of developing high depressive symptoms in all models (final model odds
ratio [OR]: 3.90; 95% confidence interval [CI]: 1.85,8.20). For noncurrent
smokers, although in bivariate analyses, baseline high depressive symptoms
increased the risk of heavy smoking nearly threefold, multivariate modeling
revealed that baseline high depressive symptoms were not predictive of heavy
smoking when controlling for other determinants of smoking in teens. Previous
experimentation with smoking was the strongest predictor of becoming a heavy
smoker (OR: 3.04; 95% CI: 1.93,4.88). CONCLUSIONS: In contrast to common dictum,
depression does not seem to be an antecedent to heavy cigarette use among teens.
However, current cigarette use is a powerful determinant of developing high
depressive symptoms.
PMID- 11015519
TI - Racial differences in access to the kidney transplant waiting list for children
and adolescents with end-stage renal disease.
AB - CONTEXT: Renal transplantation is the treatment of choice for pediatric patients
with end-stage renal disease (ESRD). Black patients wait longer for kidney
transplants than do white patients. OBJECTIVE: To determine whether the increased
time to transplantation for black pediatric patients is attributable not only to
a shortage of suitable donor organs, but also to racial differences in the time
from a child's first treatment for ESRD until activation on the cadaveric kidney
transplant waitlist. DESIGN: National longitudinal cohort study. SETTING: US
Medicare-eligible, pediatric ESRD population. PATIENTS: Children and adolescents
=19 years old at the time of their first dialysis for ESRD between 1988 and
1993, followed through 1996. Patients who received living donor renal transplants
were excluded from study. MAIN OUTCOME MEASURES: Time from first dialysis for
ESRD until activation on the kidney transplant waiting list, relative hazard of
activation on the waiting list for black compared with white pediatric patients.
RESULTS: Comparisons of the time from first dialysis for ESRD to waitlisting
among the 2162 white (60.7%) and 1122 black (31.5%) patients studied using
survival analysis revealed that blacks were less likely to be waitlisted at any
given time in follow-up. In multivariate analysis, even after controlling for
patient age, gender, socioeconomic status, geographic region, incident year of
renal failure, and cause of ESRD, blacks were 12% less likely to be waitlisted
than were whites at any point in time (relative hazard:. 88: 95% confidence
interval:.79-.97). CONCLUSIONS: Racial disparities in access to the renal
transplant waiting list exist in pediatrics. Whether these disparities are
attributable to differences in time of presentation to a nephrologist, physician
bias in identification of transplant candidates, or patient preferences warrants
further study.
PMID- 11015520
TI - Biphasic anaphylactic reactions in pediatrics.
AB - OBJECTIVES: The objectives of this study were to: 1) determine the incidence of
biphasic reactions in children with anaphylaxis; 2) establish what risk factors
can predict progression to a biphasic reaction; and 3) assess the utility of
inpatient observation for patients whose anaphylaxis appears to have resolved.
METHODS: We performed a retrospective analysis of all children admitted to
Children's Hospital inpatient service between 1985 and 1999 with acute
anaphylaxis. Data were collected from the medical records regarding past medical
history, presenting signs and symptoms, treatment, and hospital course. Patients
were considered to have resolution of anaphylaxis if they were documented to have
cessation of all symptoms and needed no therapy for at least 1 hour. Biphasic
reactions were defined as a worsening of symptoms requiring new therapy after
resolution of anaphylaxis. Significant biphasic reactions were defined as those
requiring oxygen, vasopressors, intubation, subcutaneous epinephrine, or
unscheduled bronchodilator treatments. Patients were considered to benefit from a
24-hour observation period if they had a significant biphasic reaction within 24
hours of admission. RESULTS: Of 108 anaphylactic episodes, 2 (2%) were fatal, and
1 (1%) was a protracted anaphylactic reaction. Among the remaining 105 children
with resolution of anaphylaxis, 6 (6%) [95% confidence (CI): 2, 12] had biphasic
reactions, of which 3 (3%) [95% CI:.6, 8] were significant. Of those who had a
biphasic reactions, the median time from the onset of symptoms to the initial
administration of subcutaneous epinephrine was 190 minutes, versus 48 minutes for
those without a biphasic reaction. Patients with or without biphasic reactions
did not differ significantly in the incidence of initial epinephrine use, initial
steroid use, or serious respiratory or cardiovascular symptoms on initial
presentation. Two of 105 (2%) [95% CI:.2, 7] patients clinically benefitted from
a 24-hour observation period. CONCLUSIONS: We found an overall incidence of
biphasic reactions of 6%, and an incidence of significant biphasic reactions of
3%, among pediatric patients admitted with anaphylaxis. Delayed administration of
subcutaneous epinephrine was associated with an increased incidence of biphasic
reactions. Approximately 2% of patients with anaphylaxis potentially benefitted
from a 24-hour period of observation after symptoms had resolved.
PMID- 11015521
TI - Dexamethasone treatment of virilizing congenital adrenal hyperplasia: the ability
to achieve normal growth.
AB - OBJECTIVE: To assess whether treatment of virilizing congenital adrenal
hyperplasia (CAH) with long-acting glucocorticoids is associated with favorable
growth outcomes. METHOD: We examined the long-term growth of 17 boys and 9 girls
with CAH treated with dexamethasone (.27 +/-.01 mg/m(2)/day). RESULTS: For
individuals with comparable bone age (BA) and chronological age (CA) at the onset
of dexamethasone therapy, males were 2.8 +/-.8 years (mean +/- standard error of
the mean; n = 13) and females were 2.4 +/- 1.0 years (n = 6). Males were treated
for 7.3 +/- 1.1 years (DeltaCA) over which time the change in BA (DeltaBA) was
7.0 +/- 1.3 years, and the change in height age (DeltaHA) was 6.9 +/- 1.1 years.
Females were treated for 6.8 +/- 1.3 years, over which time the DeltaBA was 6.5
+/- 1.0 years, and the DeltaHA was 6.3 +/-.8 years. During treatment 17
ketosteroid excretion rates were normal for age and 17-hydroxyprogesterone values
were 69.6 +/- 18 ng/dL. Testicular enlargement was first detected at 10.7 +/-.8
years and breast tissue at 9.9 +/- 1.2 years. Three boys and 1 girl had final
heights of 171. 8 +/- 6 cm and 161 cm, respectively, compared with midparental
heights of 176.1 +/- 4.1 cm and 160 cm. Predicted adult heights for 6 other boys
and 5 girls were 176.8 +/- 2.0 cm and 161.4 +/- 2.8 cm, respectively, compared
with midparental heights of 174.6 +/- 1.4 cm and 158.2 +/- 2.0 cm. Statural
outcomes were less favorable for 7 children started on dexamethasone when BAs
were considerably advanced, although height predictions increased during therapy.
CONCLUSIONS: These observations show that children treated with dexamethasone for
CAH can achieve normal growth with the convenience of once-a-day dosing in most
cases.congenital adrenal hyperplasia, dexamethasone, growth.
PMID- 11015522
TI - The Tagum study I: analysis and clinical correlates of mercury in maternal and
cord blood, breast milk, meconium, and infants' hair.
AB - OBJECTIVES: To compare the indicators and levels of mercury (Hg) exposure in the
mother with those in the fetal compartments, and determine its effects on the
newborn. METHODS: Hg levels using atomic absorption spectrophotometry were
determined in maternal blood, breast milk, cord blood, infants' hair, and
meconium of 78 consecutive mother-infant pairs in a community with high Hg
pollution. The prevalence and levels of Hg both in meconium and in cord blood
were correlated with maternal and infant risk factors. RESULTS: The prevalence of
Hg in the fetal compartments was higher than in the maternal fluid compartments.
Hg was present in 6.4% of maternal blood and 6.4% of breast milk, as compared
with 16.7% of cord blood, 31.6% of infants' hair, and 46.1% of meconium. Forty
six percent of infants with Hg in cord blood had none in meconium, whereas 80.6%
with Hg in meconium had none in cord blood. Hg was not present in the maternal
blood of all infants (n = 36) with Hg in their meconium. Among those with
detectable Hg, the mean levels were: mothers' blood 24 parts per billion +/-
5.47, cord blood 53.3 parts per billion +/- 37.49, and meconium 48.6 +/- 43.48.
Quantitative measurement in hair was not done because of insufficient sample.
Paired comparisons were all significant between Hg levels in the mothers' blood
and meconium, mothers' blood and cord blood, and cord blood and meconium.
Regression analysis showed Hg levels in meconium to be correlated with prevalence
of Hg in infants' hair, length of stay in Tagum, and meconium-stained amniotic
fluid. Fisher's Exact probability test showed that the prevalence of Hg in
meconium was significantly related to the prevalence of Hg in the mothers' blood
and length of stay in Tagum. The prevalence of Hg in cord blood was significantly
related to the prevalence in the mothers' blood. Regression analysis of levels of
Hg in cord blood showed a significant relation to levels in mothers' blood
(.0001), prevalence in infants' hair (.0126), gestational age (GA) (.0091), and
head circumference (HC) (.0469). By quadrant analysis of weight against HC in 66
full-term infants all of 4 infants weighing an average of >3000 g at birth and
with HCs lower than the fifth percentile had Hg in meconium. CONCLUSION: The
higher prevalence and levels of Hg in the fetal compartments reflect the ease of
placental transfer with fetal trapping. Hg determinations in the mothers' blood
underestimate the degree and extent of fetal exposure. There is a significant
difference in each compartment's ability to reflect Hg exposure of the fetus. A
small HC may be associated with the presence of Hg in meconium. Hg in meconium
should be measured in addition to cord blood to determine the load of fetal Hg.
PMID- 11015524
TI - Patterns of alcohol and drug use in adolescents can be predicted by parental
substance use disorders.
AB - OBJECTIVE: To examine the specificity of risk for alcohol or drug abuse or
dependence (substance use disorders [SUDs]) in offspring exposed to particular
subtypes of parental SUDs. METHODS: The original sample was derived from 2 groups
of index children: 140 attention-deficit/hyperactivity disorder (ADHD) probands
and 120 non-ADHD comparison probands. These groups had 174 and 129 biological
siblings and 279 and 240 parents, respectively. RESULTS: Independent of familial
risk, exposure to parental SUDs predicted SUDs in the offspring. Controlling for
duration of exposure, we found that adolescence was a critical developmental
period for exposure to parental SUDs. Because all our analyses controlled for
social class, ADHD status, and parental lifetime history of SUDs, these results
show that exposure to parental SUDs predicts offspring SUDs independently of
these risk factors. CONCLUSIONS: These results support the critical importance of
familial environmental risk factors for the development of SUDs in youth in
general and particularly in those at high risk for these disorders. These results
highlight adolescence as a critical period for the deleterious effects of
exposure to parental SUDs, supporting the need to develop preventive and early
intervention strategies targeted at adolescents at high risk for SUDs.
PMID- 11015523
TI - Teacher-assessed behavior of children prenatally exposed to cocaine.
AB - OBJECTIVE: Prenatal cocaine exposure has been associated with alterations in
neonatal behavior and more recently a dose-response relationship has been
identified. However, few data are available to address the long-term behavioral
effects of prenatal exposures in humans. The specific aim of this report is to
evaluate the school-age behavior of children prenatally exposed to cocaine.
METHODS: All black non-human immunodeficiency virus-positive participants in a
larger pregnancy outcomes study who delivered singleton live born infants between
September 1, 1989 and August 31, 1991 were eligible for study participation.
Staff members of the larger study extensively screened study participants during
pregnancy for cocaine, alcohol, cigarettes, and other illicit drugs. Prenatal
drug exposure was defined by maternal history elicited by structured interviews
with maternal and infant drug testing as clinically indicated. Cocaine exposure
was considered positive if either history or laboratory results were positive.
Six years later, 665 families were contacted; 94% agreed to participate. The
child, primary caretaker (parent), and, when available, the biologic mothers were
tested in our research facilities. Permission was elicited to obtain blinded
teacher assessments of child behavior with the Achenbach Teacher's Report Form
(TRF). Drug use since the child's birth was assessed by trained researchers using
a structured interview. RESULTS: Complete laboratory and teacher data were
available for 499 parent-child dyads, with a final sample size for all analyses
of 471 (201 cocaine-exposed) after the elimination of mentally retarded subjects.
A comparison of relative Externalizing (Aggressive, Delinquent) to Internalizing
(Anxious/Depressed, Withdrawn, Somatic Complaints) behaviors of the offspring was
computed for the TRF by taking the difference between the 2 subscales to create
an Externalizing-Internalizing Difference (T. M. Achenbach, personal
communication, 1998). Univariate comparisons revealed that boys were
significantly more likely to score in the clinically significant range on total
TRF, Externalizing-Internalizing, and Aggressive Behaviors than were girls.
Children prenatally exposed to cocaine had higher Externalizing-Internalizing
Differences compared with controls but did not have significantly higher scores
on any of the other TRF variables. Additionally, boys prenatally exposed to
cocaine were twice as likely as controls to have clinically significant scores
for externalizing (25% vs 13%) and delinquent behavior (22% vs 11%). Gender,
prenatal exposures (cocaine and alcohol), and postnatal risk factors (custody
changes, current drug use in the home, child's report of violence exposure) were
all related to problem behaviors. Even after controlling for gender, other
prenatal substance exposures, and home environment variables, cocaine-exposed
children had higher Externalizing-Internalizing Difference scores. Prenatal
exposure to alcohol was associated with higher total score, increased attention
problems, and more delinquent behaviors. Prenatal exposure to cigarettes was not
significantly related to the total TRF score or any of the TRF subscales.
Postnatal factors associated with problem behaviors included both changes in
custody status and current drug use in the home. Change in custody status of the
cocaine-exposed children, but not of the controls, was related to higher total
scores on the TRF and more externalizing and aggressive behaviors. Current drug
use in the home was associated with higher scores on the externalizing and
aggressive subscales. CONCLUSIONS: Results of this study suggest gender-specific
behavioral effects related to prenatal cocaine exposure. Prenatal alcohol
exposure also had a significant impact on the TRF. Postnatal exposures, including
current drug use in the home and the child's report of violence exposure, had an
independent effect on teacher-assessed child behavioral problems. (ABSTRACT
TRUNCATE
PMID- 11015525
TI - Year 2000 position statement: principles and guidelines for early hearing
detection and intervention programs. Joint Committee on Infant Hearing, American
Academy of Audiology, American Academy of Pediatrics, American Speech-Language
Hearing Association, and Directors of Speech and Hearing Programs in State Health
and Welfare Agencies.
PMID- 11015526
TI - The unnecessary epidemic of folic acid-preventable spina bifida and anencephaly.
PMID- 11015527
TI - Commentary on cerebral intravascular oxygenation correlates with mean arterial
pressure in critically ill premature infants.
PMID- 11015528
TI - Verve and Jolt: deadly new Internet drugs.
AB - As regulatory agencies have increased restrictions on the sale and marketing of
gamma-hydroxybutyrate (GHB), they have been frustrated by the appearance of
precursor molecules such as gamma-butyrolactone (GBL) that have become widely
available over the Internet. These dangerous precursors are vigorously marketed
to adolescents and young adults as dietary supplements that increase muscle mass
and enhance sexual performance with seductive names such as Verve and Jolt, both
easily recognizable teen icons. We present the case of an adolescent who ingested
both of these GBL products 2 weeks apart, resulting in life-threatening
respiratory depression and emergent intubation on both occasions. The GBL
toxidrome, necessary acute interventions, and public health implications are
reviewed. We urge all health care providers to report similar cases immediately
to the FDA MedWatch system. Gamma-butyrolactone, gamma-hydroxybutyrate,
respiratory insufficiency, central nervous system depressants, substance abuse.
PMID- 11015529
TI - Role of naloxone in newborn resuscitation.
AB - OBJECTIVE: Because of questions about the basis for the use of naloxone in
resuscitation of the newborn, we wished to evaluate the use of naloxone at our
institution and an affiliated hospital. METHODOLOGY: Evaluation of the actual use
of naloxone at a university hospital and a community hospital: we document
naloxone use by daily survey for a month in one; in the other, we perform a
retrospective record review of 1 year's use. RESULTS: The university hospital had
240 births during February, 1998. Naloxone was given twice: once, 7 minutes
before delivery to a woman at term who had received opiates about 2 hours
previously; and once, intramuscularly, to a premature infant for apnea, before
being intubated. The community hospital had 2044 births during fiscal 1998.
Twenty-six neonates were identified as having received naloxone. Of the 26, 13
received naloxone without needing ventilatory support; all 13 with respiratory
depression had a predisposing perinatal complication. CONCLUSION: The use of
naloxone in practice may not conform to the American Academy of Pediatrics'
guidelines for use in resuscitation of the newborn. The use of naloxone in
resuscitation of the newborn should be reevaluated.
PMID- 11015530
TI - Respiratory syncytial virus infection in patients with phagocyte defects.
AB - Patients with phagocyte defects frequently develop bacterial or fungal
pneumonias, but they are not considered to be at increased risk for viral
infections. We describe 3 patients with known phagocyte immunodeficiencies who
developed lower respiratory tract infections (LRTI) caused by respiratory
syncytial virus (RSV). All 3 patients had dense pneumonias as indicated by
computed tomography scan of the lungs and RSV was recovered. We conclude that RSV
can present as a dense pneumonia in patients with phagocyte defects. Along with
common pathogens causing LRTI, RSV should be considered in the differential
diagnosis. Viral cultures as well as rapid antigen detection assays for
respiratory viruses should be included in the evaluation of LRTI in patients with
phagocyte defects. respiratory syncytial virus, phagocyte, immunodeficiency,
pneumonia.
PMID- 11015532
TI - "Blue balls": A diagnostic consideration in testiculoscrotal pain in young
adults: A case report and discussion.
PMID- 11015531
TI - Visual field constriction in children with epilepsy on vigabatrin treatment.
AB - Vigabatrin is considered the drug of choice for infantile spasms and simple and
complex partial epilepsy in childhood. Its mechanism of action relies on the
irreversible inhibition of gamma-aminobutyric acid (GABA) transaminase. Since
June 1997 several articles have been published reporting visual field
constriction in adult patients on vigabatrin therapy. Recently, 7 pediatric
patients, 1 on vigabatrin monotherapy and 6 on add-on therapy with visual field
constriction have been described. We have observed 30 pediatric patients with
epilepsy (14 boys and 16 girls), ages ranging from 4 to 20 years (mean: 11 years
and 2 months) treated with vigabatrin for infantile spasms, simple and complex
partial epilepsy, who had never complained of ophthalmologic disturbances. Twenty
one patients underwent complete routine ophthalmologic examination (fundus oculi,
visual acuity, intraocular pressure, and visual field tests); 9 children (<6
years old) underwent only fundus examination, because collaboration was lacking.
We report on 4 children showing constriction of visual field, prevailing in nasal
hemifield. In 1 child, visual abnormalities were stable even 10 months after
vigabatrin discontinuation, while in another a greater improvement was observed 5
months after discontinuation. The possible mechanisms have been discussed and the
cone dysfunction, connected with GABA augmentation in the outer retina, has been
outlined. We suggest a possible protocol to control visual abnormalities in
epileptic children.
PMID- 11015533
TI - Isolated large third-trimester intracranial cyst on fetal ultrasound: fact or
fiction?
AB - OBJECTIVE: To distinguish the fact from artifact of an isolated, large,
intracranial cyst on prenatal sonography (PSG). BACKGROUND: The use of PSG is
rapidly increasing with most obstetric ultrasounds occurring in general community
settings like small hospitals and clinics with personnel who have variable
training, experience, and interest levels. In contrast, most PSG articles and
books are produced in large subspecialty centers with concentrated referral bases
plus both highly-trained and experienced personnel. DESIGN/METHODS: We report a
series of 2 normal newborn patients who had a large prenatal unilateral
intracranial cyst diagnosed by PSG in the 10 years between July of 1989 and 1999
at a rural community hospital. The newborns had imaging studies at birth and
their neurodevelopmental progress was followed for several years. Textbook,
bibliography and computerized Medline (1966-present) searches including prenatal
ultrasound, observer variation, diagnostic errors, reproducibility of results,
sensitivity and specificity, accuracy, central nervous system, false-positive,
prenatal diagnosis, and brain were examined starting in August 1996 for reports.
RESULTS: There were 4079 obstetric ultrasounds performed in 3.5 years, January
1996 through July 1999 at this rural community facility. This rate extrapolates
to a total of 11 654 obstetric ultrasounds over the 10-year study period in which
the 2 cases of intracranial cyst artifact occurred. Thus, the incidence of 2
intracranial cyst artifacts was estimated as 2/11 654 PSG, a .0002% false
positive rate. CONCLUSIONS: This is the first report of the occurrence of PSG
artifacts in a community facility. Artifact is a real problem and needs to be
specified in differential diagnoses. There are ways to decrease sonographic
artifact-or at least to recognize it-so our estimates at a community hospital for
its occurrence are presented with the relevant technical and ethical issues. None
of these issues have been previously reported in the pediatric literature. Our
false-positive rate for large intracranial cyst compares favorably with other
reports. Our estimate may inflate our denominator by reporting scans rather than
the number of fetuses scanned, and our numerator may miss cases that moved from
the community. Confusion differentiating PSG artifact from reality often occurs
when interpreting static or frozen real-time images. The signs that sonogram
images may be artifacts include defects that: extend outside the fetal body;
change shape, size and echogenecity with different scan planes; are not seen on
all examinations; and are isolated in an otherwise normal fetus. Failure to offer
quality PSG in clinical settings where it is available restricts access of
pregnant women to the diagnosis of fetal anomalies, and therefore restricts
access to the options of pregnancy termination, fetal therapy like fetal surgery,
and delivery options of timing, setting, and mode. We suggest a multidisciplinary
approach to prenatal abnormalities like isolated third trimester unilateral
intracranial cyst in both primary and tertiary care settings aids interpretation
followed by expectant conservative management without elaborate, risky, or
terminal interventions.
PMID- 11015534
TI - Successful long-term peritoneal dialysis in a very low birth weight infant with
renal failure secondary to feto-fetal transfusion syndrome.
PMID- 11015535
TI - Use of a peak flow meter for positive feedback in psychogenic cough.
PMID- 11015536
TI - The role of the pediatrician in transitioning children and adolescents with
developmental disabilities and chronic illnesses from school to work or college.
American Academy of Pediatrics. Committee on Children With Disabilities.
AB - The role of the pediatrician in transitioning children with disabilities and
chronic illnesses from school to work or college is to provide anticipatory
guidance and to promote self-advocacy and self-determination. Knowledge of the
provisions of the key federal laws affecting vocational education is essential
for the pediatrician's successful advocacy for patients.
PMID- 11015537
TI - Children in pickup trucks. American Academy of Pediatrics. Committee on Injury
and Poison Prevention.
AB - Pickup trucks have become increasingly popular in the United States. A recent
study found that in crashes involving fatalities, cargo area passengers were 3
times more likely to die than were occupants in the cab. Compared with restrained
cab occupants, the risk of death for those in the cargo area was 8 times higher.
Furthermore, the increased use of extended-cab pickup trucks and air bag-equipped
front passenger compartments creates concerns about the safe transport of
children. The most effective preventive strategies are the legislative
prohibition of travel in the cargo area and requirements for age-appropriate
restraint use and seat selection in the cab. Parents should select vehicles that
are appropriate for the safe transportation needs of the family. Physicians have
an important role in counseling families and advocating public policy measures to
reduce the number of deaths and injuries to occupants of pickup trucks.
PMID- 11015538
TI - Insurance coverage of mental health and substance abuse services for children and
adolescents: A consensus statement. American Academy of Pediatrics.
PMID- 11015539
TI - Primary care treatment of pediatric psychosocial problems: A study from pediatric
research in office settings and ambulatory sentinel practice network.
AB - OBJECTIVE: Psychosocial problems cause much of the morbidity among children, and
their frequency of presentation in primary care is growing. How is primary care
treatment of children's psychosocial problems affected by child symptoms,
physician training, practice structure, insurance, physician/patient
relationship, and family demographics? DESIGN: Questionnaire study of treatment
of psychosocial problems during office visits by children. SETTINGS: At total of
401 primary care offices from 44 US states, Puerto Rico, and Canada. PATIENTS:
From 21 150 children seen in office visits, we selected children with an
identified psychosocial problem but who were not already receiving specialty
mental health services (n = 2618 children). OUTCOME MEASURES: Clinicians'
decisions to counsel families, to refer children to mental health specialists, or
to prescribe medication. RESULTS: The treatment choices of primary care
clinicians (PCCs) were generally independent of patients' demographics or
insurance status. Clinicians' training, beliefs about mental health, and practice
structure had no effect on treatment choices. However, clinicians seeing their
own patients were more likely to prescribe medications for attention problems.
The clinician's perception about whether the parent agreed with the treatment
choice was important for every treatment modality. Counseling and referral were
more common and medication was less common when a problem was newly recognized at
the visit. CONCLUSIONS: Structural factors such as practice type, insurance
coverage, and physician training were less important for treatment than were
process factors, such as whether the visit was a psychosocial problem visit,
whether the problem was newly or previously recognized, and whether the family
and clinician were familiar with each other and in accord about treatment.
PMID- 11015540
TI - Time for a new paradigm in pediatric medical education: teaching neonatal
resuscitation in a simulated delivery room environment.
AB - OBJECTIVES: Acquisition and maintenance of the skills necessary for successful
resuscitation of the neonate are typically accomplished by a combination of
completion of standardized training courses using textbooks, videotape, and
manikins together with active participation in the resuscitation of human
neonates in the real delivery room. We developed a simulation-based training
program in neonatal resuscitation (NeoSim) to bridge the gap between textbook and
real life and to assess trainee satisfaction with the elements of this program.
METHODS: Thirty-eight subjects (physicians and nurses) participated in 1 of 9
full-day NeoSim programs combining didactic instruction with active, hands-on
participation in intensive scenarios involving life-like neonatal and maternal
manikins and real medical equipment. Subjects were asked to complete an extensive
evaluation of all elements of the program on its conclusion. RESULTS: The
subjects expressed high levels of satisfaction with nearly all aspects of this
novel program. Responses to open-ended questions were especially enthusiastic in
describing the realistic nature of simulation-based training. The major
limitation of the program was the lack of fidelity of the neonatal manikin to a
human neonate. CONCLUSION: Realistic simulation-based training in neonatal
resuscitation is possible using current technology, is well received by trainees,
and offers benefits not inherent in traditional paradigms of medical education.
PMID- 11015541
TI - Television commercial violence during nonviolent programming: the 1998 major
league baseball playoffs.
AB - OBJECTIVES: To identify the frequency of violent commercials during the major
league baseball playoffs in 1998 and to compare it with the 1996 playoffs. DESIGN
AND SETTING: All 4 World Series games televised on the Fox Television Network
(Fox), all 6 National League Championship Series (NLCS) televised by Fox, and 5
of 6 American League Championship Series (ALCS) playoff games televised by the
National Broadcasting Company (NBC) were videotaped in October 1998. The results
were compared with a similar study that analyzed the 1996 playoffs. RESULTS:
Forty-four commercials (11.0 per game) that included violent interactions were
noted during the World Series, 53 violent commercials (8.8 per game) during the
NLCS, and 40 (8.0 per game) during the ALCS for a total of 137. Of these 137
violent commercials, 78 contained at least 1 violent act, 126 contained at least
1 violent threat, and 12 contained evidence of at least 1 violent consequence.
One hundred five of the 137 violent commercials (76.6%) were television
promotions and 23 (16.8%) were for big-screen movie promotions. Twenty-three of
35 big-screen movie promotions (65.7%) were violent. Ten of the 137 violent
commercials (7.3%) contained obvious blood, of which 9 were televised by NBC.
There were, however, an additional 20 commercials televised by Fox that contained
visible blood if the videotape was slowed or paused. Sixty-three of the 137
violent commercials (46.0%) used fire and explosions, of which 53 were televised
by Fox and 10 by NBC. Guns were involved in 86 of 137 violent commercials
(62.8%), with Fox accounting for 64 (6.4 per game) and NBC accounting for 22 (4.4
per game). Knives were used in 1 violent commercial on both Fox and NBC.
Comparisons that can be made to 1996 include the following: 1) violent
commercials during the World Series (both televised by Fox) increased from 10.1
to 11.0 per game; and 2) violent commercials during the ALCS (both televised by
NBC) increased from 6.0 to 8.0 per game. CONCLUSION: Commercials during the 1998
major league playoffs were similar in violent content, compared with 1996. The
violent commercials continue to consist primarily of promotions for television
programs and big-screen movies. It continues to be counterintuitive to find such
commercials in family-oriented programming and makes it difficult for parents to
avoid exposing their children to this form of violence.
PMID- 11015542
TI - Environmental tobacco smoke exposure among urban children.
AB - BACKGROUND: Environmental tobacco smoke (ETS) exposure is a well-known health
hazard for children. Poor urban children may be at increased risk of exposure
from nonparental sources of tobacco smoke. The unique problems of ETS exposure in
urban children have previously not been well-defined. OBJECTIVES: This study was
conducted: 1) to identify the sources of ETS exposure for children attending a
hospital-based pediatric resident practice; and 2) to examine caregivers'
perceptions of the pediatrician's role and action in addressing ETS exposure.
DESIGN: Questionnaires were administered to a convenience sample of 174
caregivers of children visiting a children's hospital-based resident practice. A
structured face-to-face interview was used. RESULTS: All caregivers agreed to
participate in the study. Most of the caregivers interviewed were mothers
(87.9%). Although only 14% of caregivers were smokers, 49.4% reported caring for
at least 1 smoke-exposed child. Most smoke exposure occurred in the home; smoking
is allowed in the home of 75% of the children who live with a smoker (48/64).
Thirty-four percent of the caregivers who reported no smoking in the home
reported having a child who spends time in homes where other people smoke. Most
exposure outside the home occurred at a grandparent's home. A ban on smoking in
the home did not eliminate a child's risk of residential smoke exposure but did
predict whether smoking occurred in the same room as the child. All caregivers
reported believing that tobacco smoke is harmful. Approximately one half of
caregivers who smoke (54.2%) would like smoking cessation advice from the child's
pediatrician. Interest in receiving advice on helping others quit smoking was
also high (51.3%) among nonsmoking caregivers who cared for a smoke-exposed
child. CONCLUSIONS: Nonparental sources of ETS exposure are reported to be common
in urban children. Children may be exposed to tobacco smoke even in homes where
smoking is banned. Many caregivers would like help from pediatricians in reducing
children's exposure to tobacco smoke.
PMID- 11015543
TI - Long-term effect of dust control on blood lead concentrations.
AB - BACKGROUND: Dust control is recommended to prevent children's exposure to
residential lead hazards, but the long-term effect of dust control on children's
exposure to environmental lead is unknown. OBJECTIVE: To determine the effect of
dust control on children's exposure to lead, as measured by blood lead
concentration at 48 months of age. DESIGN: A randomized, controlled trial.
Setting. Rochester, New York. PARTICIPANTS: A total of 275 urban children were
randomized at 6 months of age; 189 (69%) were available for the 48-month follow
up blood test. Intervention. Children and their families were randomly assigned
to an intervention group that received cleaning equipment and up to 8 visits by a
trained lead hazard control advisor or to a control group. The intervention was
terminated when the children were 24 months of age. OUTCOME MEASURES: Geometric
mean blood lead concentration and prevalence of elevated blood lead concentration
(ie, >/=10 microg/dL, >/=15 microg/dL, and >/=20 microg/dL), by group assignment.
RESULTS: For children with 48-month blood tests, baseline geometric mean blood
lead concentrations were 2.8 microg/dL (95% confidence interval [CI]: 2.6, 3.0);
there were no significant differences in baseline characteristics or lead
exposure by group assignment. At 48 months of age, the geometric mean blood lead
was 5.9 microg/dL (95% CI: 5.3, 6.7) for the intervention group and 6.1 microg/dL
(95% CI: 5.5,6.9) for the control group. The percentage of children with a 48
month blood lead >/=10 microg/dL, >/=15 microg/dL, and >/=20 microg/dL was 19%
versus 19%, 2% versus 9%, and 1% versus 2% in the intervention and control
groups, respectively. CONCLUSIONS: We conclude that dust control, as performed by
families and in the absence of lead hazard controls to reduce ongoing
contamination from lead-based paint, was not effective in preventing children's
exposure to residential lead hazards.
PMID- 11015544
TI - Relations of parental obesity status to physical activity and fitness of
prepubertal girls.
AB - OBJECTIVE: To determine whether physical activity and fitness differ among normal
weight-for-height, multiethnic, prepubertal girls whose parents are lean, obese,
or both. SETTING: Conducted in Houston, Texas. STUDY PARTICIPANTS: Normal-weight
white, black, and Hispanic prepubertal girls (mean age +/- standard deviation:
8.5 +/-.4 years) participated in this study. Girls were recruited according to
parental leanness or obesity defined as follows: girls with 2 lean parents (LN
group; n = 30); girls with 2 obese parents (OB group; n = 27); and girls with 1
lean and 1 obese parent (LNOB group; n = 44). Intervention. Each child wore a
heart rate monitor for two 24-hour periods, underwent a treadmill exercise test,
answered an activity questionnaire, and completed energy expenditure measurements
by basal calorimetry and doubly labeled water. OUTCOME MEASURES: The amount of
time spent above 125% and 150% of basal heart rate (BHR) was calculated during
each 24-hour period (n = 84). Fitness (n = 97), habitual physical activity (n =
101), and physical activity level (PAL = total energy expenditure/basal metabolic
rate; n = 101) were also measured. RESULTS: The times spent above 125% and 150%
of BHR were similar among LN, LNOB, and OB groups. Black girls spent less time
than did white girls on the weekend above 125% BHR and above 150% BHR. No
significant familial or ethnic differences in peak oxygen consumption or habitual
physical activity were observed. PALs were as follows: LN = 1.6 +/-.21; LNOB =
1.64 +/-.27; OB = 1.58 +/-. 20; white = 1.63 +/-.23; black = 1.58 +/-.24; and
Hispanic = 1.65 +/-.25. PAL was related to time spent above 125% BHR and 150% BHR
(r =.31,.39). CONCLUSIONS: Physical activity and fitness of normal-weight
prepubertal girls predisposed to obesity did not differ from girls without a
family history of obesity. obesity, children, energy metabolism, exercise, heart
rate monitoring.
PMID- 11015545
TI - Aerobic fitness, not energy expenditure, influences subsequent increase in
adiposity in black and white children.
AB - BACKGROUND: Low levels of energy expenditure and aerobic fitness have been
hypothesized to be risk factors for obesity. Longitudinal studies to determine
whether energy expenditure influences weight gain in whites have provided
conflicting results. To date, no studies have examined this relationship in
blacks or whether aerobic fitness influences weight gain in white or black
children. METHODS: One hundred fifteen children, 72 white (55 girls and 17 boys)
and 43 black (24 girls and 19 boys) were recruited for this study. Aerobic
fitness, resting, total, and activity-related energy expenditure and body
composition were measured at baseline. The children returned annually for 3 to 5
repeated measures of body composition. The influence of the initial measures of
energy expenditure and fitness on the subsequent rate of increase in adiposity
was examined, adjusting for initial body composition, age, ethnicity, gender, and
Tanner stage. Because 20 children did not attain maximum oxygen consumption, the
sample size for the combined analysis was 95. RESULTS: Initial fat mass was the
main predictor of increasing adiposity in this cohort of children, with greater
initial fat predicting a higher rate of increase of adiposity. There was also a
significant negative relationship between aerobic fitness and the rate of
increasing adiposity (F(1,82) = 3.92). With every increase of.1 L/minute of
fitness, there was a decrease of.081 kg fat per kg of lean mass gained. None of
the measures of energy expenditure significantly predicted increasing adiposity
in white or black children. CONCLUSIONS: Initial fat mass was the dominant factor
influencing increasing adiposity; however, aerobic fitness was also a significant
independent predictor of increasing adiposity in this cohort of children.
Resting, total, or activity-related energy expenditure did not predict increasing
adiposity. It seems that aerobic fitness may be more important than absolute
energy expenditure in the development of obesity in white or black children.
energy expenditure, fitness, longitudinal, obesity.
PMID- 11015546
TI - Infant immunization with acellular pertussis vaccines in the United States:
assessment of the first two years' data from the Vaccine Adverse Event Reporting
System (VAERS).
AB - OBJECTIVE: To evaluate the safety of infant immunization with acellular pertussis
vaccines in the United States. BACKGROUND: The US Food and Drug Administration
approved the first acellular pertussis vaccine for use in infants in the United
States on July 31, 1996. OUTCOME MEASURES: Adverse events in the United States
after infant immunization with pertussis-containing vaccines, representing
temporal (but not necessarily causal) associations between vaccinations and
adverse events. DATA SOURCE: Reports to the Vaccine Adverse Event Reporting
System (VAERS), a passive national surveillance system. DESIGN: Reports
concerning infant immunization against pertussis between January 1, 1995 (when
whole-cell vaccine was in exclusive use) and June 30, 1998 (when acellular
vaccine was in predominant use) were analyzed, if the reports were entered into
the VAERS database by November 30, 1998. RESULTS: During the study, there were
285 reports involving death, 971 nonfatal serious reports, and 4514 less serious
reports after immunization with any pertussis-containing vaccine. For 1995 there
were 2071 reports; in 1996 there were 1894 reports; in 1997 there were 1314
reports, and in the first half of 1998 there were 491 reports. Diphtheria-tetanus
pertussis vaccine (DTP) was cited in 1939 reports, diphtheria-tetanus-whole-cell
pertussis-Haemophilus influenzae type b vaccine (DTPH) in 2918 reports, and
diphtheria-tetanus-acellular pertussis vaccine (DTaP) in 913 reports. The annual
number of deaths during the study was 85 in 1995, 82 in 1996, 77 in 1997, and 41
in the first half of 1998. The annual number of reported events categorized as
nonfatal serious (defined as events involving initial hospitalization,
prolongation of hospitalization, life-threatening illness, or permanent
disability) to VAERS for all pertussis-containing vaccines declined: 334 in 1995,
311 in 1996, 233 in 1997, and 93 in the first half of 1998. Similarly, the annual
number of less serious reports to VAERS for pertussis-containing vaccines
declined: 1652 in 1995, 1501 in 1996, 1004 in 1997, and 357 in the first half of
1998. A comparison of the adverse event profiles (proportional distributions) for
DTaP, DTP, and DTPH, as well as an analysis of specific adverse events considered
in a 1991 Institute of Medicine report on the safety of diphtheria-tetanus
pertussis vaccine, did not identify any new, clear safety concerns. CONCLUSIONS:
These findings reflect the administration of millions of doses of acellular
pertussis vaccine and are reassuring with regard to the safety of marketed
acellular pertussis vaccines. VAERS data, although subject to the limitations of
passive surveillance, support the prelicensure data with regard to the safety of
the US-licensed acellular pertussis vaccines that we evaluated.
PMID- 11015547
TI - Hypotonic-hyporesponsive episodes reported to the Vaccine Adverse Event Reporting
System (VAERS), 1996-1998.
AB - BACKGROUND: A hypotonic-hyporesponsive episode (HHE) is the sudden onset of
hypotonia, hyporesponsiveness, and pallor or cyanosis that occurs within 48 hours
after childhood immunizations. This syndrome has been primarily associated with
pertussis-containing vaccines administered to children <2 years of age, and has
been estimated to occur once every 1750 diphtheria-tetanus-pertussis (DTwP)
vaccinations. Previous studies of HHE were limited by small numbers of cases and,
sometimes, by limited details of the event. OBJECTIVES: To characterize a large
number of HHE cases reported to the Vaccine Adverse Event Reporting System
(VAERS), to assist clinicians in identifying HHE, and to assist researchers in
investigating the risk factors, cause, and pathogenesis of this syndrome.
METHODS: More than 40,000 VAERS reports received between 1996 and 1998 were
screened for HHE by a computer algorithm and reviewed, and a telephone follow-up
questionnaire was administered to the witness of HHE. RESULTS: There were 215 HHE
cases, all nonfatal. The median age of onset of HHE was 4.0 months (range: 1.1
107 months). Over half of the reports (53%) concerned females. The median birth
weight was 3. 36 kg (range: 1.27-4.96 kg); 4.7% had a birth weight <2500 g. The
median interval between vaccination and HHE was 210 minutes (range: 1 minute-2
days). Among children with HHE who were <24 months of age, the episode occurred
within 5 minutes in only 8.5%, compared with 66.7% of children with HHE >24
months of age. There were no relevant findings regarding family medical history
or the mothers' gestational history. Nearly all of the children (98.6%) returned
to their prevaccination state according to the telephone questionnaire; median
time to return was 6 hours (range: 1 minute- 4 months). The 3 children reported
as not returning to their prevaccination state all had VAERS reports submitted
after they developed conditions (autism, complex partial epilepsy, and
developmental delays with infantile spasms) that are not known to be causally
associated with immunization. The vast majority of children (93%) with HHE
received a pertussis-containing vaccine, either diphtheria-tetanus-acellular
pertussis (DTaP, 28%), DTwP (11%), or diphtheria-tetanus-pertussis-Haemophilus
influenzae type b (DTwP-HIB, 61%). During the HHE episode, 90.1% of the children
had pallor and 49% had cyanosis. Because of the HHE event, 6.8% of children had
had all vaccines withheld as of the date of the interview. Of the remainder,
66.5% of children have had 1 or more subsequent vaccinations or vaccine
components withheld, and 26.7% have not had any subsequent vaccinations withheld.
Only 1 child was reported to have had a repeat episode of HHE, occurring after
hepatitis B vaccination. From 1996 to 1998, the number of HHE reports decreased
from 99 to 38, when the predominant pertussis vaccine administered to infants
changed from whole-cell to acellular. CONCLUSION: This study represents the
largest published case series of children with HHE and supports the generally
benign, self-limited, nonrecurrent nature of this syndrome. Although HHE has been
less frequently reported to VAERS after increased use of DTaP, HHE does occur
after the administration of DTaP and other nonpertussis-containing vaccines.
Although most parents and pediatricians withheld the pertussis component of
subsequent vaccinations, many did not, with no reported adverse events occurring
in the children after the subsequent immunizations. Restricting the definition of
HHE to a more narrow age range (eg, <2 years of age) is also proposed because
most of the older children probably experienced vasovagal syncope rather than HHE
within 5 minutes of immunization.
PMID- 11015548
TI - Interferon-alpha and ribavirin in treating children and young adults with chronic
hepatitis C after malignancy.
AB - OBJECTIVE: Chronic hepatitis C is a major long-term problem for children who
survive cancer. Interferon (IFN)-alpha has been shown to be effective in treating
patients with chronic hepatitis C; however, the rate of sustained response is
low. Combining IFN-alpha and ribavirin (RBV) has been shown to significantly
improve the response in adult patients with chronic hepatitis C. The aim of this
pilot study was to evaluate the efficacy and safety of a combined virostatic
treatment with IFN-alpha and RBV in a small cohort of children and adolescents
with chronic hepatitis C and previous malignancy. METHODS: Twelve patients with a
history of a hematooncologic disease (median follow-up: 13.5 years; range: 7-14.7
years) and chronic hepatitis C were treated with recombinant IFN-alpha-2a (6
megaunits/m(2) body surface area, 3 times a week, subcutaneously) combined with
RBV (15 mg/kg body weight/day, orally) for 12 months. They were tested monthly
for blood counts and liver function, and for serum virus concentrations
(hepatitis C virus RNA by polymerase chain reaction) every 3 months. RESULTS: At
the end of the treatment, hepatitis C virus RNA could not be detected in the
serum of 8 of the 12 patients; 2 of these patients relapsed soon after therapy
withdrawal, whereas 6 patients maintained in sustained virologic and biochemical
remission (follow-up: 12 months). Treatment-induced toxicity was moderate and
reversible with influenza-like symptoms and a decrease in blood counts in all 12
patients, alopecia in 5 of the 12, hemolysis in 4 of the 12, and weight loss of
>10% in 2 of the 12. CONCLUSIONS: As demonstrated in adults with chronic
hepatitis C, treatment with IFN-alpha and RBV also seems to be an effective and
safe therapeutic option for children and adolescents with chronic hepatitis C
after malignancy.
PMID- 11015549
TI - Sources of infection among persons with acute hepatitis A and no identified risk
factors during a sustained community-wide outbreak.
AB - CONTEXT: Hepatitis A is a common vaccine-preventable disease in the United
States. Most cases occur during community-wide outbreaks, which can be difficult
to control. Many case-patients have no identified source. OBJECTIVE: To identify
foodborne and household sources of hepatitis A during a community-wide outbreak.
DESIGN: Serologic and descriptive survey. SETTING: Salt Lake County, Utah.
PARTICIPANTS: A total of 355 household contacts of 170 persons reported with
hepatitis A during May 1996 to December 1996, who had no identified source of
infection; and 730 food handlers working in establishments where case-patients
had eaten. MAIN OUTCOME MEASURE: Prevalence of immunoglobulin M antibodies to
hepatitis A virus (IgM anti-HAV) among household and food service contacts.
RESULTS: Overall, 70 household contacts (20%) were IgM anti-HAV-positive,
including 52% of children 3 to 5 years old and 30% of children <3 years old. In
multivariate analysis, the presence of a child <3 years old (odds ratio [OR]:
8.8; 95% confidence limit [CL]: 2.1,36) and a delay of >/=14 days between illness
onset and reporting (OR: 7. 9; 95% CL: 1.7,38) were associated with household
transmission. Of 18 clusters of infections linked by transmission between
households, 13 (72%) involved unrecognized infection among children <6 years old.
No food handlers were IgM anti-HAV-positive. CONCLUSION: During a community-wide
outbreak, HAV infection among children was common, was frequently unrecognized,
and may have been an important source of transmission within and between
households. Transmission from commercial food establishments was uncommon.
Ongoing vaccination of children may prevent future outbreaks.
PMID- 11015550
TI - Late-onset neutropenia in very low birth weight infants.
AB - BACKGROUND: Neutropenia, defined as absolute neutrophil count (ANC) <1500/mm(3),
affects 6% to 58% of premature infants in the first week of life. This early
onset neutropenia in premature infants has previously been correlated with
sepsis, maternal hypertension, severe asphyxia, and periventricular hemorrhage.
Late-onset neutropenia, defined as ANC <1500/mm(3) at a postnatal age of >/=3
weeks, has not been previously reported. OBJECTIVES: The purposes of this study
were to determine the prevalence of late-onset neutropenia in very low birth
weight (VLBW) infants and to examine the factors that may be associated with this
phenomenon. METHODS: A weekly complete blood cell count (CBC) was performed
routinely in all premature infants with birth weight =1500 g (n = 225) admitted
to the neonatal intensive care in a 3-year period who survived until discharge.
CBC and differentials were recorded at day 1, day 3, and then weekly until
discharge. The clinical data of the study infants were collected by reviewing the
medical records retrospectively. RESULTS: Late-onset neutropenia was detected in
51 infants (22%). In both neutropenic (n = 51) and nonneutropenic infants (n =
174), ANC increased postnatally, remained above 5000/mm(3) for the first 3 weeks
of life, and had a marked decrease at approximately 4 weeks of age. Thereafter,
ANC decreased to a level of approximately 1400/mm(3) in the neutropenic infants
and 4000/mm(3) in the nonneutropenic infants. The neutropenic infants had a
significantly lower nadir ANC, lower hemoglobin, and higher reticulocyte count
than did the nonneutropenic infants with similar platelet counts. None of the
study infants received erythropoietin during their hospitalization. This late
onset neutropenia occurred at postnatal age of 6 +/- 2 weeks (range: 3-10 weeks).
The duration of neutropenia was 1.7 +/-.7 weeks (range: 1-3 weeks). All of the
neutropenic infants had anemia of prematurity with high reticulocyte count and
normal platelet count. The neutropenic infants were stable, growing on full oral
feedings, and had no signs or symptoms of sepsis. No adverse effects of late
onset neutropenia were apparent in these infants. CONCLUSION: Late-onset
neutropenia is a common incidental finding in stable, growing VLBW infants that
has not been previously reported. Late-onset neutropenia is a phenomenon that
occurs in anemic premature infants who have marked reticulocytosis. Normal
regulation of hematopoiesis is accompanied by a balance between colony
stimulating factors, such as erythropoietin and granulocyte colony-stimulating
factor, which regulate erythropoiesis and granulopoiesis. We speculate that
imbalance of these factors with increased reticulocytopoiesis in response to
anemia of prematurity may explain this phenomenon. We recommend avoiding
institution of aggressive, potentially harmful therapy for this phenomenon in
healthy, growing VLBW infants.
PMID- 11015551
TI - Raccoon roundworm (Baylisascaris procyonis) encephalitis: case report and field
investigation.
AB - Baylisascaris procyonis is a common and widespread parasite of raccoons in the
United States and Canada. With large raccoon populations occurring in many areas,
the potential risk of human infection with B procyonis is high. We report a case
of severe raccoon roundworm (B procyonis) encephalitis in a young child to
illustrate the unique clinical, diagnostic, and treatment aspects, as well as
public health concerns of B procyonis infection. Acute and convalescent serum and
cerebrospinal fluid samples from the patient were tested for antibodies against B
procyonis to assist in documenting infection. An extensive field survey of the
patient's residence and the surrounding community was performed to investigate
raccoon abundance and to determine the extent of raccoon fecal contamination and
B procyonis eggs in the environment. The patient evidenced serologic conversion,
and the field investigation demonstrated a raccoon population far in excess of
anything previously reported. There was abundant evidence of B procyonis eggs
associated with numerous sites of raccoon defecation around the patient's
residence and elsewhere in the community. Because B procyonis can produce such
severe central nervous system disease in young children, it is important that
pediatricians are familiar with this infection. The public should be made aware
of the hazards associated with raccoons and B procyonis to hopefully prevent
future cases of B procyonis infection.
PMID- 11015552
TI - Vulvar carcinoma in a 12-year-old girl with vertically acquired human
immunodeficiency virus infection.
AB - We report the first case of a girl with vertically acquired human
immunodeficiency virus (HIV) infection, who developed invasive squamous cell
carcinoma of the vulva at 12 years of age. Lesions resembling bowenoid papulosis
covered the perianal area as well. She underwent a nonmutilating surgical
excision of the infiltrating lesion. More than 3 years later, her clinical
condition is excellent, although dysplastic, noninfiltrating multifocal lesions
persist. This case highlights the need to perform careful periodic genital
examinations in all HIV-infected children and adolescents born to HIV-positive
mothers.
PMID- 11015553
TI - Hemophagocytic syndrome: A misleading complication of visceral leishmaniasis in
children--a series of 12 cases.
AB - OBJECTIVE: To describe the difficulties in diagnosing visceral leishmaniasis (VL)
when revealed by hemophagocytic syndrome (HS) in young children. DESIGN:
Retrospective study of patients identified over a 17-year period in French
pediatric units. RESULTS: This series comprises 12 cases of VL that were either
revealed (n = 11) or complicated (on starting treatment with antimony salts [n =
1]) by HS. Clinical manifestations were those of severe VL with sustained high
fever and hepatosplenomegaly in children in very poor condition. Biological
manifestations always included pancytopenia, marked hypofibrinogenemia and
hypertriglyceridemia, hepatic cytolysis, and prominent hemophagocytosis on the
bone marrow smear. These features led to transfer to a hematology unit. Ten
children were very young (<38 months) at onset (and consequently at infection).
Signs of autoimmunity (Coombs' test-positive erythrocytes, antinuclear factors,
and various autoantibodies) were found in 4 cases and were probably secondary to
polyclonal B cell activation. Serologic tests for Leishmania were negative at
onset in 6 children, and no amastigotes were found on the first marrow smear in 8
of 12 cases despite extensive search. Seven patients had not visited foreign
countries. All these factors explain the initial diagnostic confusion. Three
cases were initially misdiagnosed as familial erythrophagocytic
lymphohistiocytosis or infection-associated HS, and these patients were treated
with etoposide (once for 5 months) to control the HS after failure of steroids.
The diagnostic delay in these cases was 50, 74, and 134 days. When VL was finally
diagnosed, amphotericin B monotherapy was effective in 4 cases. Eight patients
were treated with antimony salts; 4 were cured, 3 required adjunctive treatment,
and 1 worsened (HS) and was cured with steroids and liposomal amphotericin.
Regardless of the type of therapy, all 12 children are presumed cured with a mean
follow-up of 7 years (range: 6 months-16 years). CONCLUSIONS: A diagnosis of VL
should, therefore, be seriously considered in all young patients with HS exposed
to visceralizing Leishmania sp in Southern Europe. Clinicians and
cytopathologists must be aware of the association. Early diagnosis of VL will
minimize unnecessary hospitalization and potentially harmful investigations and
treatments.
PMID- 11015554
TI - Revolution and renaissance.
PMID- 11015555
TI - Novel mechanism of hypertension revealed by cell-specific targeting of human
angiotensinogen in transgenic mice.
AB - We tested the hypothesis that the tissue-specific intrarenal renin-angiotensin
system (RAS) can participate in the regulation of blood pressure independently of
its endocrine counterpart, by generating two transgenic models that differ in
their tissue-specific expression of human angiotensinogen (AGT). Human AGT
expression was driven by its endogenous promoter in the systemic model and by the
kidney androgen-regulated protein promoter in the kidney-specific model. Using
molecular, biochemical, and physiological measurements, we demonstrate that human
AGT mRNA and protein are restricted to the kidney in the kidney-specific model.
Plasma ANG II was elevated in the systemic model but not in the kidney-specific
model. Nevertheless, blood pressure was markedly elevated in both the systemic
and kidney-specific transgenic mice. Acute administration of the selective ANG II
AT-1 receptor antagonist losartan lowered blood pressure in the systemic model
but not in the kidney-specific model. These results provide evidence for the
potential importance of the intrarenal RAS in blood pressure regulation by
showing that expression of AGT specifically in the kidney leads to chronic
hypertension independently of the endocrine RAS.
PMID- 11015557
TI - Exploring the topography of physiological genomics.
PMID- 11015556
TI - The agouti gene product stimulates pancreatic [beta]-cell Ca2+ signaling and
insulin release.
AB - Ubiquitous expression of the mouse agouti gene results in obesity and
hyperinsulinemia. Human agouti is expressed in adipose tissue, and we found
recombinant agouti protein to stimulate lipogenesis in adipocytes in a Ca(2+)
dependent fashion. However, adipocyte-specific agouti transgenic mice only became
obese in the presence of hyperinsulinemia. Because intracellular Ca(2+)
concentration ([Ca(2+)](i)) is a primary signal for insulin release, and we have
shown agouti protein to increase [Ca(2+)](i) in several cell types, we examined
the effects of agouti on [Ca(2+)](i) and insulin release. We demonstrated the
expression of agouti in human pancreas and generated recombinant agouti to study
its effects on Ca(2+) signaling and insulin release. Agouti (100 nM) stimulated
Ca(2+) influx, [Ca(2+)](i) increase, and a marked stimulation of insulin release
in two beta-cell lines (RIN-5F and HIT-T15; P < 0. 05). Agouti exerted comparable
effects in isolated human pancreatic islets and beta-cells, with a 5-fold
increase in Ca(2+) influx (P < 0.001) and a 2.2-fold increase in insulin release
(P < 0.01). These data suggest a potential role for agouti in the development of
hyperinsulinemia in humans.
PMID- 11015558
TI - Functional genomics: technological challenges and opportunities.
AB - In April, the Merck Genome Research Institute and the National Cancer Institute's
Cancer Genome Anatomy Project, both supporters of functional genomics technology
development and research, brought together a group of 27 scientists working at
the forefront of this new field. Here we report on the presentations,
discussions, and outcomes from this highly interactive and stimulating meeting
held at the Banbury Center.
PMID- 11015559
TI - Differential response to dietary fat in large (LG/J) and small (SM/J) inbred
mouse strains.
AB - The "large" (LG/J) and "small" (SM/J) inbred mouse strains differ for a wide
variety of traits related to body size and obesity. Ninety-three LG/J and SM/J
mice were divided into two treatment categories and fed a moderately high-fat
diet (21% kcal fat) or a low-fat diet (12% kcal fat) from weaning to necropsy.
Strain differences in obesity-related traits and differential response to dietary
fat increases were analyzed using ANOVA. LG/J animals grow faster from 3 to 10
wk, have longer tails, and have heavier body weight, liver weight, and fat pad
weight than SM/J animals. SM/J animals grow faster after 10 wk of age and have
higher fasting glucose levels than LG/J animals. SM/J mice were more responsive
to increased dietary fat than LG/J mice for growth after 10 wk, necropsy weight,
liver weight, fat pad weights, and fasting glucose levels (in males). The growth
from 3 to 10 wk had a much greater response in the LG/J strain, whereas tail
length had no response. This pattern of dietary response is similar to that
expected under the "thrifty" phenotype hypothesis. Genes affecting strain
differences and the differential response of the strains to dietary fat can be
successfully mapped in the intercross of the LG/J and SM/J strains. This
intercross provides an excellent multigenic model for the genetic basis of
complex traits and diseases related to body size and obesity.
PMID- 11015561
TI - Cloning and analysis of unique human glutaminase isoforms generated by tissue
specific alternative splicing.
AB - Three human glutaminase (hGA) isoforms were identified, two of which represent
isoforms previously unidentified in any species. One isoform contains an open
reading frame with high homology with the rat kidney-type glutaminase, suggesting
that this isoform represents the human kidney-type glutaminase, hKGA. A second
isoform, termed hGAC, contains an open reading frame that matches hKGA except for
a unique COOH-terminal amino acid sequence. In addition, a third human
glutaminase isoform was identified from a computer search and on further analysis
was found to represent an additional unique isoform, hGAM. hKGA is expressed
predominantly in brain and kidney but not in liver, hGAC is expressed principally
in cardiac muscle and pancreas but not in liver or brain, and hGAM is expressed
solely in cardiac and skeletal muscle. hGAC is the predominant isoform expressed
by a human breast cancer cell line that exhibits a high rate of glutamine
utilization and glutaminase activity. Genomic Southern analysis as well as
isolation and analysis of five glutaminase genomic clones suggested that all
three hGA isoforms originate from the same locus and therefore represent mRNA
species that are produced by tissue-specific alternative splicing of a single pre
mRNA. Furthermore, an RT-PCR assay was developed that can be used to easily
differentiate between hKGA and hGAC mRNA species.
PMID- 11015560
TI - Functional alterations in adult rat myocytes after overexpression of
phospholamban with use of adenovirus.
AB - An increased phospholamban (PLB)-to-sarco(endo)plasmic reticulum Ca(2+)-ATPase
(SERCA) ratio has been suggested to contribute to the slowing of relaxation in
failing human ventricle. We have used an adenoviral vector carrying the sequence
for PLB to increase this ratio in isolated adult rat ventricular myocytes, and we
have examined the functional consequences. With use of adenoviral vectors, the
PLB content of adult rat myocytes was increased 2.73-fold, with SERCA2a levels
unchanged. Maximum contraction amplitude of PLB-overexpressing myocytes was
decreased to 6.9 +/- 0.3% shortening compared with 11.2 +/- 0.8% for 24-h
controls (Con; P < 0.001, 5 preparations, 103 myocytes). Maximum rates of
shortening and relengthening were also significantly decreased. Ca(2+) transient
amplitudes were slightly depressed, and time to 50% decay of the transients was
significantly increased: 237 +/- 18 (n = 14 myocytes) and 432 +/- 32 ms in Con
and PLB (n = 15) myocytes, respectively (P < 0.001). The amount of Ca(2+) in the
sarcoplasmic reticulum stores was reduced by 21% (P < 0.05). Relaxation was
significantly slower in PLB than in Con myocytes when the Na(+)/Ca(2+) exchanger
was blocked but not when sarcoplasmic reticulum Ca(2+) uptake was inhibited.
Adenovirus infection with Ad.RSV.PLB was therefore able to produce functional
changes in adult cardiac myocytes within 24 h, consistent with overexpression of
PLB and similar to those seen in failing human heart.
PMID- 11015562
TI - Phenotypic differences in cardiovascular regulation in inbred rat models of
aerobic capacity.
AB - The Dark Aouti (DA) inbred strain of rats has superior aerobic treadmill running
capacity compared with the Copenhagen (COP) strain of inbred rats. This
difference in aerobic capacity provides a model to explore the genetic basis of
variation in this trait. The present study evaluated intermediate phenotypic
differences between 10 male COP inbred rats and 10 male DA inbred rats that might
contribute to the difference in aerobic capacity between the strains. Five
autonomically regulated cardiovascular variables were evaluated during rest or
exercise by measuring the response to autonomic antagonists. The DA rat had
enhanced autonomic function for the regulation of peripheral blood flow and
cardiac output. Specifically, at rest the DA rats had significantly more
sympathetic (123 +/- 8 vs. 99 +/- 7 beats/min) and parasympathetic (35 +/- 5 vs.
12 +/- 3 beats/min) tonus for heart rate control and more sympathetic support of
blood pressure (70 +/- 7 vs. 38 +/- 6 mmHg) compared with the COP rats. During
three graded levels of treadmill exercise the DA rats had higher blood pressures
(16% on average) and higher heart rates (4% on average) relative to the COP rats.
In addition, the DA rats had a 27% greater heart weight-to-body weight ratio
compared with the COP strain of rats (3.63 +/- 0.08 vs. 2.85 +/- 0.07 g/kg). All
five of these intermediate phenotypes could participate as variables causative of
the difference in treadmill running capacity between the DA and COP strains of
rats.
PMID- 11015563
TI - A high-throughput MS-PCR method on MADGE gels for ANG II type-1 receptor A1166C
polymorphism.
AB - We have developed a highly accurate, low-cost, single-step, mutagenically
separated polymerase chain reaction (MS-PCR) method for the determination of
angiotensin II type-1 receptor (AT(1)) A1166C gene polymorphism. The genotypes
are determined using the microtiter array diagonal gel electrophoresis (MADGE)
system. We have compared the MS-PCR method with allele-specific oligonucleotide
hybridization and Dde I digestion techniques for determining the AT(1) A1166C
genotype. The combination of MS-PCR and MADGE serves as a model for high
throughput single-nucleotide polymorphism genotyping in large population studies.
PMID- 11015564
TI - GIST: A web tool for collecting gene information.
AB - As the human genome is sequenced and annotated, an important step in future
genetic studies of complex traits and diseases will be the identification of
relevant candidate genes. To enable such compilations, it would be useful to
collate all necessary and available genetic information for each candidate gene.
To this end, we have created a web tool (http://genome.cwru.edu/gist/gist.html+
++) to allow the rapid cataloging of currently available genetic data. This tool,
called GIST (or "Gene Information Search Tool"), allows an investigator to search
the major genomic databases containing gene and marker information from a single
query point. To prove the utility of GIST, a catalog of 150 hypertension
candidate genes was created. This resource collates all available nucleotide and
amino acid sequence data, expression data, chromosomal map location, and genetic
marker interval for each gene, collected from on-line databases. These data can
be used to guide genetic studies of hypertension.
PMID- 11015566
TI - Why FRET over genomics?
AB - Genetic information is being uncovered quickly and in vast amounts through the
largely automated sequencing of genomes from all kinds of organisms. As this
information becomes available, enormous challenges are emerging on three levels:
first, functions will have to be assigned to individual gene products; second,
factors that influence the expression level of these gene products will have to
be identified; and third, allelic variants that act alone or in combination to
give rise to complex traits will have to be characterized. Because of the sheer
size of genomes, methods that can streamline or automate these processes are
highly desirable. Fluorescence is an attractive readout for such high-throughput
tasks because of the availability of equipment designed to detect light-emitting
compounds with great speed and high capacity. The following is an overview of the
achievements and potential of fluorescence resonance energy transfer (FRET) as
applied in three areas of genomics: the identification of single-nucleotide
polymorphisms, the detection of protein-protein interactions, and the genomewide
analysis of regulatory sequences.
PMID- 11015565
TI - Genes differentially expressed in medulloblastoma and fetal brain.
AB - Serial analysis of gene expression (SAGE) was used to identify genes that might
be involved in the development or growth of medulloblastoma, a childhood brain
tumor. Sequence tags from medulloblastoma (10229) and fetal brain (10692) were
determined. The distributions of sequence tags in each population were compared,
and for each sequence tag, pairwise chi2 test statistics were calculated.
Northern blot was used to confirm some of the results obtained by SAGE. For 16
tags, the chi2 test statistic was associated with a P value < 10(-4). Among those
transcripts with a higher expression in medulloblastoma were the genes for ZIC1
protein and the OTX2 gene, both of which are expressed in the cerebellar germinal
layers. The high expression of these two genes strongly supports the hypothesis
that medulloblastoma arises from the germinal layer of the cerebellum. This
analysis shows that SAGE can be used as a rapid differential screening procedure.
PMID- 11015567
TI - Genetic analysis of modifying loci on mouse chromosome 1 that affect disease
severity in a model of recessive PKD.
AB - Using a cross between C57BL/6J and FVB/N mice, we have confirmed the localization
on chromosome 1 of a modifying locus that affects the severity of polycystic
kidney disease (PKD) in the juvenile cystic kidney (jck) mouse. Despite the
highly significant contribution of this locus in F2 progeny of a cross between
C57BL/6J and DBA/2J mice (4), a series of congenic strains carrying regions of
chromosome 1 on a DBA/2J background did not show a severe disease phenotype. One
possible explanation for these results is that this phenotype is caused by two
linked loci, which have been separated in the congenic lines that were generated.
This hypothesis is supported by the demonstration that severe PKD occurs in mice
carrying a large congenic interval.
PMID- 11015568
TI - Constants and scientific progress.
PMID- 11015570
TI - Localization of a blood pressure QTL on rat chromosome 1 using Dahl rat congenic
strains.
AB - We previously reported that markers on rat chromosome 1 are genetically linked to
blood pressure in an F(2) population derived from Dahl salt hypertension
sensitive (S) and Lewis (LEW) rats. Because there was evidence for more than one
blood pressure quantitative trait locus (QTL) on chromosome 1, an initial
congenic strain introgressing a large 118-centimorgan (cM) segment of LEW
chromosome 1 into the S background had been constructed. This initial congenic
strain had a reduced blood pressure compared with S rats, proving the existence
of a blood pressure QTL, but not giving a good localization of the QTL. In the
present work a series of five overlapping congenic substrains were produced from
the original congenic strain in order to localize a blood pressure QTL to a 25-cM
region near the center of chromosome 1. The congenic substrains also ruled out
the Sa locus as a blood pressure QTL in the S vs. LEW comparison because the Sa
locus was contained in a congenic substrain that did not alter blood pressure.
PMID- 11015569
TI - The evolutionarily conserved Dim1 protein defines a novel branch of the
thioredoxin fold superfamily.
AB - Dim1 is a small evolutionarily conserved protein essential for G2/M transition
that has recently been implicated as a component of the mRNA splicing machinery.
To date, the mechanism of Dim1 function remains poorly defined, in part because
of the absence of informative sequence homologies between Dim1 and other
functionally defined proteins or protein domains. We have used a combination of
molecular modeling and NMR structural analysis to demonstrate that approximately
125 of the 142 amino acids of human Dim1 (hDim1) define a novel branch of the
thioredoxin fold superfamily. Mutational analysis of Dim1 based on the predicted
fold indicates that alterations in the region corresponding to the thioredoxin
active site do not affect Dim1 activity. However, removal of a very short carboxy
terminal extension generates a dominant negative form of the protein [hDim1-(1
128)] that when overproduced induces cell cycle arrest in G2, via a mechanism
likely to involve alteration of Dim1 association with partner molecules. In sum,
this study identifies the Dim1 proteins as a novel sixth branch of the
thioredoxin superfamily involved in cell cycle.
PMID- 11015571
TI - Molecular genetics of chromosome translocations involving EWS and related family
members.
AB - Many types of sarcomas are characterized by specific chromosomal translocations
that appear to result in the production of novel, tumor-specific chimeric
transcription factors. Many of these show striking similarities: the emerging
picture is that the amino-terminal domain of the fusion product is donated by the
Ewing's sarcoma gene (EWS) or a related member from the same gene family, whereas
the carboxy-terminal domain often consists of a DNA-binding domain derived from
one of a number of transcription factors. Given the observation that the
different translocation partners of the EWS protooncogene are associated with
distinct types of sarcomas, the functional consequence of fusing EWS (or a
related family member) to a different DNA-binding domain can only be understood
in the context of functional studies that define the specificity of action of the
different fusion products. An understanding of the molecular structure and
function of these translocations provides new methods for diagnosis and novel
targets for therapeutics.
PMID- 11015572
TI - Differential expression of putative transbilayer amphipath transporters.
AB - The aminophospholipid translocase transports phosphatidylserine and
phosphatidylethanolamine from one side of a bilayer to another. Cloning of the
gene encoding the enzyme identified a new subfamily of P-type ATPases, proposed
to be amphipath transporters. As reported here, mammals express as many as 17
different genes from this subfamily. Phylogenetic analysis reveals the genes to
be grouped into several distinct classes and subclasses. To gain information on
the functions represented by these groups, Northern analysis and in situ
hybridization were used to examine the pattern of expression of a panel of
subfamily members in the mouse. The genes are differentially expressed in the
respiratory, digestive, and urogenital systems, endocrine organs, the eye, teeth,
and thymus. With one exception, all of the genes are highly expressed in the
central nervous system (CNS); however, the pattern of expression within the CNS
differs substantially from gene to gene. These results suggest that the genes are
expressed in a tissue-specific manner, are not simply redundant, and may
represent isoforms that transport a variety of different amphipaths.
PMID- 11015573
TI - Physiological consequences of ectopic agouti gene expression: the yellow obese
mouse syndrome.
AB - This review summarizes primary and downstream phenotypic manifestations, with
emphasis on altered responsiveness to environmental stimuli, of dominant yellow
mutations at the mouse agouti locus. Obvious effects include hyperinsulinemia,
obesity, stimulation of somatic growth and tumorigenesis, and coat color.
Downstream influences of hyperinsulinemia and obesity on the individual's
physiology determine important components of the obese yellow agouti mouse
syndrome. Collectively, the phenotypic aberrations described support the concept
that identical genomes are expressed in a spectrum of physiological phenotypes
that reflect the complex interdependence of gene-regulated physiological pathways
and processes in the organism throughout extended, but temporally ordered,
periods of fetal and neonatal development and aging. This summary identifies
important areas for additional research and provides integrated information
required for a systematic approach to the development of interventions for common
adult human health problems.
PMID- 11015574
TI - A genome scan for QTL influencing milk production and health traits in dairy
cattle.
AB - A genome scan was conducted in the North American Holstein-Friesian population
for quantitative trait loci (QTL) affecting production and health traits using
the granddaughter design. Resource families consisted of 1,068 sons of eight
elite sires. Genome coverage was estimated to be 2,551 cM (85%) for 174 genotyped
markers. Each marker was tested for effects on milk yield, fat yield, protein
yield, fat percentage, protein percentage, somatic cell score, and productive
herd life using analysis of variance. Joint analysis of all families identified
marker effects on 11 chromosomes that exceeded the genomewide, suggestive, or
nominal significance threshold for QTL effects. Large marker effects on fat
percentage were found on chromosomes 3 and 14, and multimarker regression
analysis was used to refine the position of these QTL. Half-sibling families from
Israeli Holstein dairy herds were used in a daughter design to confirm the
presence of the QTL for fat percentage on chromosome 14. The QTL identified in
this study may be useful for marker-assisted selection and for selection of a
refined set of candidate genes affecting these traits.
PMID- 11015575
TI - Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing,
and expression of full-length cDNA.
AB - The sensitive technique of RT-PCR was used to identify cholesteryl ester
hydrolase (CEH) expressed in human macrophages. This enzyme is thought to
regulate the availability of intracellular free cholesterol for efflux. The
expected 667-bp product was obtained starting with RNA from human peripheral
blood and THP-1 monocytes and macrophages. The cDNA for human macrophage CEH was
then cloned by PCR-based screening of a lambda-gt11 cDNA library. The full-length
cDNA was sequenced and found to exhibit 76% homology (at the nucleotide and
conceptually translated protein level) to hepatic CEH, an enzyme shown to be
involved in hepatic cholesterol homeostasis and regulated by cholesterol at the
transcription level via sterol response elements in the proximal promoter.
Identification of the conserved catalytic triad (Ser(221, His(468), and
Glu354)) and the SEDCLY motif places human macrophage CEH in the family of
carboxylesterases. A greater than 20-fold increase in CEH activity was observed
when COS-1 and COS-7 cells were transiently transfected with an eukaryotic
expression vector, pcDNA3.1/V5/His-TOPO, containing the cDNA for human macrophage
CEH. Using this full-length cDNA as a probe, a 2.2-kb transcript was identified
by Northern blot analysis of total RNA from human peripheral blood and THP -1
macrophages. Overexpression of human macrophage CEH resulted in an impairment of
upregulation of low-density lipoprotein (LDL) receptor mRNA in Chinese hamster
ovary (CHO-K1) cells grown in cholesterol-deficient environment. These data
identify the human macrophage CEH, demonstrate its expression in human peripheral
blood macrophage and human macrophage cell line, THP-1, and suggest its role in
the intracellular cholesteryl ester metabolism.
PMID- 11015576
TI - A novel mutation in FGFR-3 disrupts a putative N-glycosylation site and results
in hypochondroplasia.
AB - Fibroblast growth factor receptor 3 (FGFR3) is a glycoprotein that belongs to the
family of tyrosine kinase receptors. Specific mutations in the FGFR3 gene are
associated with autosomal dominant human skeletal disorders such as
hypochondroplasia, achondroplasia, and thanatophoric dysplasia. Hypochondroplasia
(HCH), the mildest form of this group of short-limbed dwarfism disorders, results
in approximately 60% of cases from a mutation in the intracellular FGFR3-tyrosine
kinase domain. The remaining cases may either be caused by defects in other FGFR
gene regions or other yet unidentified genes. We describe a novel HCH mutation,
the first found outside the common mutation hot spot of this condition. This
point mutation, an N328I exchange in the extracellular Ig domain III of the
receptor, seems to be unique as it affects a putative N-glycosylation site that
is conserved between different FGFRs and species. The amino acid exchange itself
most probably has no impact on the three-dimensional structure of the receptor
domain, suggesting that the phenotype is the result of altered receptor
glycosylation and its pathophysiological consequences.
PMID- 11015577
TI - Inflammation influences vascular remodeling through AT2 receptor expression and
signaling.
AB - The AT(2) receptor, which exerts growth inhibitory effects in cell culture, is
present scantily in the adult vasculature but is reexpressed after vascular
injury. To examine the in vivo role of this receptor in vascular diseases, we
developed a mouse model of vascular remodeling and compared the responses in wild
type (Agtr2(+)) and AT(2) receptor knockout (Agtr2(-)) mice. Polyethylene cuff
placement on the femoral artery led to the vascular expression of cytokines, the
transcriptional factor interferon regulatory factor-1 (IRF-1), and both the AT(1)
and AT(2) receptors. Although the expressions of IRF-1 and AT(1) receptor were
induced to comparable levels in both the Agtr2(+) and Agtr2(-) mice, the
neointimal lesion size and the smooth muscle cell proliferation were twice
greater in the Agtr2(-) than in the Agtr2(+) mouse. Correlated with this
difference, AT(2) receptor expression was induced predominantly in the smooth
muscle cells of Agtr2(+) mouse. These results demonstrate that the AT(2) receptor
plays an important role in nonocclusive inflammatory injury by mediating the
effects of inflammation on vascular smooth muscle growth inhibition.
PMID- 11015578
TI - nNOS and eNOS modulate cGMP formation and vascular response in contracting fast
twitch skeletal muscle.
AB - Nitric oxide (NO) from Ca(2+)-dependent neuronal nitric oxide synthase (nNOS) in
skeletal muscle fibers may modulate vascular tone by a cGMP-dependent pathway
similar to NO derived from NOS in endothelial cells (eNOS). In isolated fast
twitch extensor digitorum longus (EDL) muscles from control mice, cGMP formation
increased approximately 166% with electrical stimulation (30 Hz, 15 s). cGMP
levels were not altered in slow-twitch soleus muscles. The NOS inhibitor N(omega)
nitro-l-arginine abolished the contraction-induced increase in cGMP content in
EDL muscles, and the NO donor sodium nitroprusside (SNP) increased cGMP content
approximately 167% in noncontracting EDL muscles. SNP treatment but not
electrical stimulation increased cGMP formation in muscles from nNOS(-/-) mice.
cGMP formation in control and stimulated EDL muscles from eNOS(-/-) mice was less
than that obtained with similarly treated muscles from control mice. Arteriolar
relaxation in contracting fast-twitch mouse cremaster muscle was attenuated in
muscles from mice lacking either nNOS or eNOS. These findings suggest that
increases in cGMP and NO-dependent vascular relaxation in contracting fast-twitch
skeletal muscle may require both nNOS and eNOS.
PMID- 11015579
TI - Assessment of cellular profile and lung function with repeated bronchoalveolar
lavage in individual mice.
AB - In this study, we sought to develop procedures that would enable repeated
bronchoalveolar lavage (BAL) in individual mice on multiple occasions. To achieve
this objective, we first developed the procedures that would allow individual
mice to survive a whole lung lavage, and then tested whether, on subsequent days,
there was an effect of this initial BAL on the cell profile, lung permeability,
and baseline respiratory function. Our results demonstrate that the repeated
lavage procedure can be readily carried out in individual mice of different
strains on multiple occasions. The lavage procedure itself results in immediate
increases in respiratory system resistance and concomitant decreases in
compliance, but these parameters return to prelavage values by the 2nd or 3rd day
postlavage. Lavage also induces variable increases in inflammatory cells
depending on the strain used. However, in all three strains examined here (A/J,
BALB/c, and C3H/HeJ), inflammatory cell numbers returned to baseline values
within 3 days after an initial lavage procedure. The ability to perform repeated
BAL in individual mice should prove to be an extremely useful tool in a variety
of functional genomic studies in the lung.
PMID- 11015580
TI - Reverse genetics in zebrafish.
AB - The zebrafish has become a popular model system for the study of vertebrate
developmental biology because of its numerous strengths as a molecular genetic
and embryological system. To determine the requirement for specific genes during
embryogenesis, it is necessary to generate organisms carrying loss-of-function
mutations. This can be accomplished in zebrafish through a reverse genetic
approach. This review discusses the current techniques for generating mutations
in known genes in zebrafish. These techniques include the generation of
chromosomal deletions and the subsequent identification of complementation groups
within deletions through noncomplementation assays. In addition, this review will
discuss methods currently being evaluated that may improve the methods for
finding mutations in a known sequence, including screening for randomly induced
small deletions within genes and screening for randomly induced point mutations
within specific genes.
PMID- 11015581
TI - Realizing the potential of zebrafish as a model for human disease.
AB - The value of the zebrafish (Danio rerio) as a model for human disease has been
substantiated by a number of recently published papers. Several zebrafish mutants
with "human" diseases have been found, spanning a variety of human pathologies.
These successful studies utilizing the zebrafish have been made possible by the
development of key reagents such as YAC, PAC, and BAC libraries, as well as
radiation hybrid panels. With the further establishment of new tools and access
to the newly generated resources, the zebrafish is poised to serve as a novel
model for human disease.
PMID- 11015582
TI - Chips around the world: proceedings from the Nature Genetics microarray meeting.
PMID- 11015583
TI - Mass spectrometry and proteomics.
PMID- 11015584
TI - Targeting the Hprt locus in mice reveals differential regulation of Tie2 gene
expression in the endothelium.
AB - To study the in vivo expression of the murine Tie2 gene, we have targeted the
hypoxanthine phosphoribosyltransferase (Hprt) gene locus to generate two single
copy transgenic mice: T1, containing the 2,100-bp Tie2 promoter upstream from the
beta-galactosidase (LacZ) gene, and T5, which also included an enhancing element
originating from the first intron of the Tie2 gene. Comparing T1 and T5 embryos
at day E10.5 revealed differential endothelial cell-specific expression of LacZ,
whereas colocalization analyses showed that the expression was confined to
endothelial cells. Moderate reporter gene activity was observed in the brain and
kidney of T1 adults, whereas extensive LacZ gene expression was seen in the
vasculature of most organs of the T5 adults. This study demonstrates the
feasibility of targeting the Hprt locus with endothelial cell-specific sequences
to analyze the spatial-temporal expression of transgenes. Of particular
importance is the observation that the analysis of a single transgene copy in a
defined locus allows for an accurate and rapid comparison of transcriptional
activity among regulatory DNA sequences.
PMID- 11015585
TI - Targeting of human eNOS promoter to the Hprt locus of mice leads to tissue
restricted transgene expression.
AB - Phenotypic heterogeneity of the endothelium arises from cell type-specific
differences in gene expression. An understanding of the mechanisms that underlie
differential gene expression would provide important insight into the molecular
basis of vascular diversity. In standard transgenic assays, multiple copies of
heterologous DNA cassettes are randomly integrated into the mouse genome,
resulting in significant line-to-line variation in expression. To overcome these
limitations, we have targeted a single copy of a transgene that contains 1,600 bp
of the human endothelial nitric oxide synthase (eNOS) promoter coupled to the
LacZ reporter gene to the X-linked hypoxanthine phosphoribosyltransferase (Hprt)
locus of mice by homologous recombination. The transgene was inserted in either
of the orientations relative to that of the Hprt gene. In mice derived from
multiple embryonic stem (ES) cell clones, the expression pattern was limited to a
subset of endothelial cells, cardiomyocytes, and vascular smooth muscle cells.
These findings suggest that Hprt locus targeting is a feasible tool for studying
endothelial cell-restricted gene regulation.
PMID- 11015586
TI - Encroaching genomics: adapting large-scale science to small academic
laboratories.
AB - The process of conducting biological research is undergoing a profound
metamorphosis due to the technological innovations and torrent of information
resulting from the execution of multiple species genome projects. The further
tasks of mapping polymorphisms and characterizing genome-wide protein-protein
interaction (the characterization of the proteome) will continue to garner
resources, talent, and public attention. Although some elements of these whole
genome size projects can only be addressed by large research groups, consortia,
or industry, the impact of these projects has already begun to transform the
process of research in many small laboratories. Although the impact of this
transformation is generally positive, laboratories engaged in types of research
destined to be dominated by the efforts of a genomic consortium may be negatively
impacted if they cannot rapidly adjust strategies in the face of new large-scale
competition. The focus of this report is to outline a series of strategies that
have been productively utilized by a number of small academic laboratories that
have attempted to integrate such genomic resources into research plans with the
goal of developing novel physiological insights.
PMID- 11015588
TI - Regulation of leptin by agouti.
AB - Dominant mutations at the mouse Agouti locus lead to ectopic expression of the
Agouti gene and exhibit diabetes, obesity, and yellow coat color. Obese yellow
mice are hyperinsulinemic and hyperleptinemic, and we hypothesized that Agouti
directly induces leptin secretion. Accordingly, we used transgenic mice
expressing agouti in adipocytes (under the control of aP2 promoter, aP212) to
examine changes in leptin levels. Agouti expression in adipose tissue did not
significantly alter food intake, weight gain, fat pad weight, or insulinemia;
however, the transgenic mice were hyperglycemic. We demonstrated that plasma
leptin levels are approximately twofold higher in aP212 transgenic mice compared
with their respective controls, whereas ubiquitous expression of agouti (under
the control of beta-actin promoter, BAP20) led to a sixfold increase in leptin.
Insulin treatment of aP212 mice increased adipocyte leptin content without
affecting plasma leptin levels. These findings were further confirmed in vitro in
3T3-L1 adipocytes treated with recombinant Agouti protein and/or insulin. Agouti
but not insulin significantly increased leptin secretion, indicating that insulin
enhances leptin synthesis but not secretion while Agouti increases both leptin
synthesis and secretion. This increased leptin synthesis and secretion was due to
increased leptin mRNA levels by Agouti. Interestingly, agouti regulation of
leptin was not mediated by melanocortin receptor 4, previously implicated in
agouti regulation of food intake. These results suggest that increased leptin
secretion by agouti may serve to limit agouti-induced obesity, independent of
melanocortin receptor antagonism, and indicate that interaction between obesity
genes may play a key role in obesity.
PMID- 11015587
TI - Gene expression profile in mouse myocardium after ischemia.
AB - This study was designed to elaborate a molecular profile of expressed genes
during ischemic injury to the mouse heart after surgical constriction of the left
coronary artery without reperfusion. A mouse cDNA array containing 588 known
genes was used to compare gene expression in heart RNA after 24-h ischemia with
control tissue. Alterations in gene expression on the array were supported by
relative reverse transcription-polymerase chain reaction analysis after timed
periods of ischemia. Decreased levels of the cell cycle regulator p18ink4 and the
oxidative responsive gene glutathione S-transferase were accompanied by an
upregulation of the genes associated with cardiac muscle development, alpha
myosin heavy chain and fetal myosin alkali light chain. Other stress responses
elicited by cardiac injury included an induction of Egr-1 and Egr-3 transcription
factors, as well as the apoptotic regulator Bax. Altogether, these findings
indicate that expression of genes associated with a fetal transcription program
may be involved with the post ischemic remodeling process in heart ventricles.
PMID- 11015589
TI - Genetically defined risk of salt sensitivity in an intercross of Brown Norway and
Dahl S rats.
AB - A genetic segregation analysis was performed to identify genes that cosegregate
with arterial blood pressure traits reflective of salt sensitivity. A population
of 113 F2 male rats was derived from an intercross of inbred SS/JrHsd/Mcw (Dahl
salt-sensitive) and BN/SsN/Mcw (Brown Norway) rats. Rats were maintained on an 8%
salt diet from the age of 9 to 13 wk, and arterial pressure was measured for 3 h
daily during the 4th wk of high salt intake in unanesthetized rats using
implanted arterial catheters. At the end of the 3rd day of high-salt pressure
recordings, the arterial pressure response to salt depletion was determined 1.5
days following treatment with Lasix and a low-sodium (0. 4%) diet. A genome-wide
scan using 265 polymorphic simple sequence length polymorphism (SSLP) markers
found that seven arterial pressure phenotypes determined at different times and
circumstances, and representing two distinct indexes of salt sensitivity, mapped
to the same region of rat chromosome 18. The trait of salt sensitivity was
strongly influenced by the presence of SS alleles in this region of chromosome
18, and those rats which were homozygote SS/SS exhibited a significantly greater
reduction of mean arterial pressure following sodium depletion (29 +/- 2 mmHg)
than homozygote BN/BN (17 +/- 3 mmHg) or heterozygotic (22 +/- 2 mmHg) rats. This
region of rat chromosome 18 corresponds to the long arm of human chromosome 5 and
a region of human chromosome 18 that has been linked to hypertension in humans.
Given the unlikely chance of these different blood pressure traits mapping to the
same region, we believe these data provide evidence that this region of rat
chromosome 18 plays an important role in salt-induced hypertension.
PMID- 11015590
TI - Adeno-associated virus vector transduction of vascular smooth muscle cells in
vivo.
AB - Adeno-associated virus (AAV) vectors might offer solutions for restenosis and
angiogenesis by transducing nondividing cells and providing long-term gene
expression. We investigated the feasibility of vascular cell transduction by AAV
vectors in an in vivo rabbit carotid artery model. Time course of gene
expression, inflammatory reaction to the vector, and effects of varying viral
titer, exposure time, and intraluminal pressures on gene expression were
examined. Recombinant AAV vectors with an Rous sarcoma virus promoter and
alkaline phosphatase reporter gene were injected intraluminally into transiently
isolated carotid segments. Following transduction, gene expression increased
significantly over 14 days and then remained stable to 28 days, the last time
point examined. Medial vascular smooth muscle cells were the main cell type
transduced even with an intact endothelial layer. Increasing the viral titer and
intraluminal pressure both enhanced transduction efficiency to achieve a mean of
34 +/- 7% of the subintimal layer of smooth muscle cells expressing gene product.
A mild inflammatory reaction, composed of T cells with only rare macrophages,
with minimal intimal thickening was demonstrated in 40% of transduced vessels;
inflammatory cells were not detected in sham-operated control arteries. These
findings demonstrate that AAV is a promising vector for intravascular
applications in coronary and peripheral vascular diseases.
PMID- 11015591
TI - Inactivation of one copy of the mouse neurotrophin-3 gene induces cardiac
sympathetic deficits.
AB - Whether two copies of the neurotrophin-3 (NT3) gene are necessary for proper
development of cardiac sympathetic innervation was investigated in mice carrying
a targeted inactivation of the NT3 gene. Heterozygous (+/-) and null (-/-) mutant
mice had fewer stellate ganglion neurons than did wild-type (+/+) mice at
postnatal day 0 (P0 or birth), and this deficit was maintained between adult
(P60) +/- and +/+ mice. The sympathetic innervation of the heart matured
postnatally in +/+ and +/- mice. Tyrosine hydroxylase (TH)-positive axons were
restricted largely to the epicardium at P0, were concentrated around large blood
vessels in the myocardium at P21, and were present among cardiac myocytes at P60.
Cardiac norepinephrine (NE) concentrations paralleled the growth of the
sympathetic axons into the heart. NE concentrations were equivalent among +/+, +/
, and -/- mice at birth, but differences between +/- and +/+ mice increased with
age. Adult +/- mice also exhibited lower resting heart rates and sympathetic
tonus than +/+ mice. Thus deletion of one copy of the NT3 gene translates into
anatomical, biochemical, and functional deficits in cardiac sympathetic
innervation of postnatal mice, thereby indicating a gene-dosage effect for the
NT3 gene.
PMID- 11015592
TI - Angiotensin peptides acting at rostral ventrolateral medulla contribute to
hypertension of TGR(mREN2)27 rats.
AB - We have previously demonstrated that microinjections of the selective angiotensin
(1-7) [ANG-(1-7)] antagonist, A-779, into the rostral ventrolateral medulla
(RVLM) produces a significant fall in mean arterial pressure (MAP) and heart rate
(HR) in both anesthetized and conscious rats. In contrast, microinjection of
angiotensin II (ANG II) AT(1) receptor antagonists did not change MAP in
anesthetized rats and produced dose-dependent increases in MAP when microinjected
into the RVLM of conscious rats. In the present study, we evaluated whether
endogenous ANG-(1-7) and ANG II acting at the RVLM contribute to the hypertension
of transgenic rats harboring the mouse renin Ren-2 gene, TGR(mREN2)27. Unilateral
microinjection of A-779 (0.1 nmol) produced a significant fall in MAP (-25 +/- 5
mmHg) and HR (-57 +/- 20 beats/min) of awake TGR rats. The hypotensive effect was
greater than that observed in Sprague-Dawley (SD) rats (-9 +/- 2 mmHg).
Microinjection of the AT(1) antagonist CV-11974 (0.2 nmol) produced a fall in MAP
in TGR rats (-14 +/- 4 mmHg), contrasting with the pressor effect observed in SD
rats (33 +/- 9 mmHg). These results indicate that endogenous ANG-(1-7) exerts a
significant pressor action in the RVLM, contributing to the hypertension of
TGR(mREN2)27 transgenic rats. The role of ANG II at the RVLM seems to be
dependent on its endogenous level in this area.
PMID- 11015593
TI - Comparison of human adult and fetal expression and identification of 535
housekeeping/maintenance genes.
AB - Gene expression levels of about 7,000 genes were measured in 11 different human
adult and fetal tissues using high-density oligonucleotide arrays to identify
genes involved in cellular maintenance. The tissues share a set of 535
transcripts that are turned on early in fetal development and stay on throughout
adulthood. Because our goal was to identify genes that are involved in
maintaining cellular function in normal individuals, we minimized the effect of
individual variation by screening mRNA pooled from many individuals. This
information is useful for establishing average expression levels in normal
individuals. Additionally, we identified transcripts uniquely expressed in each
of the 11 tissues.
PMID- 11015595
TI - A fuzzy logic approach to analyzing gene expression data.
AB - We have developed a novel algorithm for analyzing gene expression data. This
algorithm uses fuzzy logic to transform expression values into qualitative
descriptors that can be evaluated by using a set of heuristic rules. In our tests
we designed a model to find triplets of activators, repressors, and targets in a
yeast gene expression data set. For the conditions tested, the predictions made
by the algorithm agree well with experimental data in the literature. The
algorithm can also assist in determining the function of uncharacterized proteins
and is able to detect a substantially larger number of transcription factors than
could be found at random. This technology extends current techniques such as
clustering in that it allows the user to generate a connected network of genes
using only expression data.
PMID- 11015594
TI - The two isozymes of rat intestinal alkaline phosphatase are products of two
distinct genes.
AB - Rat intestinal alkaline phosphatases (IAP-I and -II) differ in primary structure,
substrate specificity, tissue localization, and response to fat feeding. This
study identifies two distinct genes ( approximately 5-6 kb) corresponding to each
isozyme and containing 11 exons of nearly identical size. The exon-intron
junctions are identical with those found in IAP genes from other species. The 1.7
and 1.2 bp of 5' flanking regions isolated from each gene, respectively, contain
Sp1 and gut-enriched Kruppel-like factor (GKLF) binding sites, but otherwise show
little identity. There is a potential CAAT-box 14 bp 5' to the transcriptional
start site, 36 bp upstream from IAP-I, and a TATA-box 31 bp 5' to the
transcriptional start site, 55 bp upstream from IAP-II. Transfection of these
promoter regions (linked to luciferase as a reporter gene) into a kidney cell
line, COS-7, produced the differential response to oleic acid expected from in
vivo studies, i.e., threefold increase using the 5' flanking region of IAP-II,
but not IAP-I. This response was not reproduced by 5,8,11,14-eicosatetraynoic
acid (ETYA) or clofibrate, suggesting that peroxisome proliferator response
elements are not involved. Isolation of the IAP-II gene will allow determination
of the sequences responsible for dietary fat response in the enterocyte.
PMID- 11015596
TI - Diet effects on weight gain and body composition in high growth (hg/hg) mice.
AB - Nongenetic factors such as nutrition modulate the effects of genes responsible
for overgrowth in animals. The goal of this study was to examine the importance
of genotype x diet interactions on the effects of a major locus that regulates
growth in the mouse. We have examined the phenotype of high growth (hg), a
partially recessive autosomal locus that increases growth rate and mature body
size. C57BL/6J (C57) and congenic C57BL/6J-hg/hg (HG) mice were fed three
experimental diets differing in protein and energy content from 3 to 12 wk of
age. HG mice grew faster and were, on average, 51% heavier than C57 at 12 wk of
age. Feed intake was higher in HG mice but proportional to the increase in body
weight. The magnitude of the differences in body size and composition between
lines depended on the interaction between genotype and the protein/energy ratio
of the diet. In C57, the diets modified the level of fatness without changing
adult lean mass. However, in HG the diets differentially affected both linear
growth and body composition. In general, HG had higher plasma levels of insulin
like growth factor I at 3 and 12 wk than C57. Plasma insulin did not differ
between lines, but leptin was higher for C57 mice fed a high-energy diet. These
results show that the effects of hg on growth are modulated by diet composition.
Therefore, this mutation could be a valuable model with which to study the
genetic and nutritional aspects of overgrowth disorders.
PMID- 11015597
TI - Identification of three human renin mRNA isoforms from alternative tissue
specific transcriptional initiation.
AB - We have reported that mice transgenic for 140- and 160-kb P1 phage artificial
chromosomes (PACs) containing the human renin gene express the gene in a highly
tissue-restricted and regulated manner. Herein, we demonstrate that the transgene
is also expressed appropriately throughout development. In the course of this
investigation, we identified the existence of three transcriptional isoforms of
human renin mRNA derived from the utilization of alternative transcription start
sites. The first isoform is the kidney-specific isoform, which utilizes the
classic renin promoter. The second is a brain-specific isoform, which when
previously identified in rats and mice was due to a transcription initiation site
within intron A. However, the start site in the human gene resides approximately
1,325 bp upstream of the classic promoter and encodes a new exon 1 (termed exon
1b) that splices directly to exon 2. The third isoform is lung specific and is
due to transcriptional initiation 79 bp directly upstream of exon 2, fusing
additional DNA within intron A (termed exon 1c) directly to exon 2 without
splicing. Importantly, the alternative first exons observed in the PAC transgenic
mice were identical to those used to transcribe renin in human fetal kidney,
brain, and lung, suggesting these sites are bona fide isoforms of human renin
mRNA and not artifacts of transgenesis. Moreover, the subtle differences in
tissue-specific transcriptional initiation observed in the renin gene of rats and
humans can be faithfully and accurately emulated in a transgenic model.
PMID- 11015598
TI - Blood pressure QTL that differentiate Dahl salt-sensitive and spontaneously
hypertensive rats.
AB - Our purpose was to define quantitative trait loci (QTL) for blood pressure that
differ between two widely used hypertensive rat strains, the Dahl salt-sensitive
(S) rat and the spontaneously hypertensive rat (SHR). A genome scan was done on
an F(2) (S x SHR) population fed 8% NaCl for 4 wk. Three blood pressure QTL were
detected, one on each of rat chromosomes (chr) 3, 8, and 9. For the chr 3 QTL the
SHR allele increased blood pressure, and for chr 8 and 9 the S allele increased
blood pressure. The QTL on chr 9 was exceptionally strong, having a LOD score of
7.3 and accounting for 30% of the phenotypic variance and a difference of 40 mmHg
between homozygotes. A review of the literature in conjunction with the present
data suggests that S and SHR are not different for the previously described
prominent blood pressure QTL on chr 1, 2, 10, and 13. QTL for body weight on chr
4, 12, 18, and 20, each with an effect of about 30 g, were incidentally observed.
PMID- 11015599
TI - Genetic variation in LMNA modulates plasma leptin and indices of obesity in
aboriginal Canadians.
AB - We previously showed that a rare mutation in LMNA, which encodes lamins A and C,
underlies autosomal dominant Dunnigan-type familial partial lipodystrophy (FPLD).
Because FPLD is an extreme example of genetically disturbed adipocyte
differentiation, it is possible that common variation in LMNA is associated with
obesity-related phenotypes. We therefore analyzed the relationships between the
common LMNA 1908T/C single nucleotide polymorphism (SNP) and plasma leptin and
anthropometric indices in 306 nondiabetic Canadian Oji-Cree. We found that
subjects with the LMNA 1908T/1908T genotype had significantly higher plasma
leptin than the subjects with either the 1908C/1908T or 1908C/1908C genotypes,
after adjustment for age and sex. Physical indices of obesity, such as body mass
index, percent body fat, and ratio of waist-to-hip circumference, were also
higher among Oji-Cree subjects with the LMNA 1908T/1908T genotype than the
subjects with either the 1908C/1908T or 1908C/1908C genotypes. The results
suggest that common genetic variation in LMNA may be an important determinant of
plasma leptin and obesity-related quantitative traits.
PMID- 11015600
TI - ANP in regulation of arterial pressure and fluid-electrolyte balance: lessons
from genetic mouse models.
AB - The recent development of genetic mouse models presenting life-long alterations
in expression of the genes for atrial natriuretic peptide (ANP) or its receptors
(NPR-A, NPR-C) has uncovered a physiological role of this hormone in chronic
blood pressure homeostasis. Transgenic mice overexpressing a transthyretin-ANP
fusion gene are hypotensive relative to the nontransgenic littermates, whereas
mice harboring functional disruptions of the ANP or NPR-A genes are hypertensive
compared with their respective wild-type counterparts. The chronic hypotensive
action of ANP is determined by vasodilation of the resistance vasculature, which
is probably mediated by attenuation of vascular sympathetic tone at one or
several prejunctional sites. Under conditions of normal dietary salt consumption,
the hypotensive action of ANP is dissociated from the natriuretic activity of the
hormone. However, during elevated dietary salt intake, ANP-mediated antagonism of
the renin-angiotensin system is essential for maintenance of blood pressure
constancy, inasmuch as the ANP gene "knockout" mice (ANP -/-) develop a salt
sensitive component of hypertension in association with failure to adequately
downregulate plasma renin activity. These findings imply that genetic
deficiencies in ANP or natriuretic receptor activity may be underlying causative
factors in the etiology of salt-sensitive variants of hypertensive disease and
other sodium-retaining disorders, such as congestive heart failure and cirrhosis.
PMID- 11015601
TI - Circadian rhythms in a nutshell.
AB - Living organisms on this planet have adapted to the daily rotation of the earth
on its axis. By means of endogenous circadian clocks that can be synchronized to
the daily and seasonal changes in external time cues, most notably light and
temperature, life forms anticipate environmental transitions, perform activities
at biologically advantageous times during the day, and undergo characteristic
seasonal responses. The effects of transmeridian flight and shift work are stark
reminders that although modern technologies can create "cities that never sleep"
we cannot escape the recalcitrance of endogenous clocks that regulate much of our
physiology and behavior. Moreover, malfunctions in the human circadian timing
system are implicated in several disorders, including chronic sleep disorders in
the elderly, manic-depression, and seasonal affective disorders (SAD or winter
depression). Recent progress in understanding the molecular mechanisms underlying
circadian rhythms has been remarkable. In its most basic form, circadian clocks
are comprised of a set of proteins that, by virtue of the design principles
involved, generate a self-sustaining transcriptional-translational feedback loop
with a free-running period of about 24 h. One or more of the clock components is
acutely sensitive to light, resulting in an oscillator that can be synchronized
to local time. This review provides an overview of the roles circadian clocks
play in nature, how they might have arisen, human health concerns related to
clock dysfunction, and mainly focuses on the clockworks found in Drosophila and
mice, the two best studied animal model systems for understanding the biochemical
and cellular bases of circadian rhythms.
PMID- 11015602
TI - Role of intracellular calcium in human adipocyte differentiation.
AB - Intracellular calcium ([Ca(2+)](i)) modulates adipocyte lipid metabolism and
inhibits the early stages of murine adipogenesis. Consequently, we evaluated
effects of increasing [Ca(2+)](i) in early and late stages of human adipocyte
differentiation. Increasing [Ca(2+)](i) with either thapsigargin or A23187 at 0-1
h of differentiation markedly suppressed differentiation, with a 40-70% decrease
in triglyceride accumulation and glycerol-3 phosphate dehydrogenase (GPDH)
activity (P < 0.005). However, a 1-h pulse of either agent at 47-48 h only
modestly inhibited differentiation. Sustained, mild stimulation of Ca(2+) influx
with either agouti protein or 10 mM KCl-induced depolarization during 0-48 h of
differentiation inhibited triglyceride accumulation and GPDH activity by 20-70%
(P < 0.05) and markedly suppressed peroxisome proliferator-activated receptor
gamma (PPARgamma) expression. These effects were reversed by Ca(2+) channel
antagonism. In contrast, Ca(2+) pulses late in differentiation (71-72 h or 48-72
h) markedly increased these markers of differentiation. Thus increasing
[Ca(2+)](i) appears to exert a biphasic regulatory role in human adipocyte
differentiation, inhibiting the early stages while promoting the late stage of
differentiation and lipid filling.
PMID- 11015603
TI - Global expression profiling of yeast treated with an inhibitor of amino acid
biosynthesis, sulfometuron methyl.
AB - The expression pattern of 1,529 yeast genes in response to sulfometuron methyl
(SM) was analyzed by DNA microarray technology. SM, a potent herbicide, inhibits
acetolactate synthase, a branched-chain amino acid biosynthetic enzyme. Exposure
of yeast cells to 0.2 microg/ml SM resulted in 40% growth inhibition, a Gcn4p
mediated induction of genes involved in amino acid and cofactor biosynthesis, and
starvation response. The accumulation of intermediates led to the induction of
stress response genes and the repression of genes involved in carbohydrate
metabolism, nucleotide biosynthesis, and sulfur assimilation. Extended exposure
to SM led to a relaxation of the initial response and induction of sugar
transporter and ergosterol biosynthetic genes, as well as repression of histone
and lipid metabolic genes. Exposure to 5 microg/ml SM resulted in >98% growth
inhibition and stimulated a similar initial expression change, but with no
relaxation after extended exposure. Instead, more stress response and DNA damage
repair genes become induced, suggesting a serious cellular consequence. Other
salient features of metabolic regulation, such as the coordinated expression of
cofactor biosynthetic genes with amino acid biosynthetic ones, were evident from
our data. A potential link between SM sensitivity and ergosterol metabolism was
uncovered by expression profiling and confirmed by genetic analysis.
PMID- 11015604
TI - A novel, sensitive detection system for high-density microarrays using dendrimer
technology.
AB - To improve signal detection on cDNA microarrays, we adapted a fluorescent
oligonucleotide dendrimeric signal amplification system to microarray technology.
This signal detection method requires 16-fold less RNA for probe synthesis, does
not depend on the incorporation of fluorescent dNTPs into a reverse transcription
reaction, generates a high signal-to-background ratio, and can be used to allow
for multichannel detection on a single chip. Furthermore, since the dendrimers
can be detected individually, it may be possible, by employing dendrimer-binding
standards, to calculate the numbers of bound cDNAs can be estimated. These
features make the dendrimer signal detection reagent ideal for high-throughput
functional genomics research.
PMID- 11015605
TI - Cloning a chloride conductance mediator from the apical membrane of porcine ileal
enterocytes.
AB - Attempts to attribute ileal brush-border chloride conductance to specific
proteins were pursued by screening a porcine intestinal cDNA library. A 0.94-kb
clone was identified on expression screening with a monoclonal antibody that
inhibited enterocyte brush-border chloride conductance. Further screening
approaches led to the isolation of a 3.1-kb full-length sequence called pCLCA1,
consistent with the identification of a 2.9-kb transcript through Northern
analysis. This sequence had significant homology to the CLCA gene family of
calcium-regulated chloride channels, especially to hCLCA1. However, a strong A
kinase consensus phosphorylation site in a predicted cytoplasmic loop of the
protein was a notable difference from the hCLCA1 gene product. Several porcine
exocrine epithelial tissues, including ileum, trachea, and the major salivary
glands express pCLCA1 mRNA. In situ hybridization studies localized the
expression of pCLCA1 mRNA to the crypt and villus epithelia of porcine ileum,
whereas tracheal expression was observed in both surface epithelium and
submucosal glands. In situ expression of pCLCA1 in mouse 3T3 cells induces an
ionomycin-dependent chloride conductance activity in these cells.
PMID- 11015606
TI - Interaction of genetic and environmental programming of the leptin system and of
obesity disposition.
AB - Possible adverse interactions between an usually inconspicuous genetic trait and
early environmental factors favoring the development of obesity were investigated
in rats heterozygous for the leptin receptor defect "fatty" (fa). Pups were
exposed to early postnatal overfeeding by reducing litter size from normally 10
12 to only 4. Rearing +/+ and +/fa pups from day 3 to 21 in small litters
increased fat-free dry mass and body fat, but only in the latter did a
significant interaction with genotype occur. Pronounced differences in the
responsiveness of +/+ and +/fa pups to "prophylactic" leptin treatment (from day
1 to 21) were observed, with +/fa females from small litters being nearly as fat
and unresponsive as previously reported for normally reared fa/fa pups. Clear
heterozygous differences in total hypothalamic leptin binding, but no litter size
effect, paralleling the differences in leptin responsiveness, were observed. By
early postnatal overfeeding an usually inconspicuous genetic trait may thus
become etiologic for the development of obesity via physiological changes other
than the decreased leptin binding characterizing the genetic defect.
PMID- 11015607
TI - Bradykinin B2 null mice are prone to renal dysplasia: gene-environment
interactions in kidney development.
AB - Congenital abnormalities of the kidney and urinary tract are a common cause of
end-stage renal disease in children. Host and environment factors are implicated
in the pathogenesis of aberrant renal development. However, direct evidence
linking gene-environment interactions with congenital renal disease is lacking.
We report an animal model of renal dysgenesis that is dependent on a defined
genetic defect and specific embryonic stressor. Specifically, mice that are
deficient in the bradykinin type 2 receptor gene (B(2)) and salt loaded during
embryogenesis acquire an aberrant kidney phenotype and die shortly after birth.
In contrast, B(2) mutant mice maintained on normal sodium intake or salt-loaded
wild-type mice do not develop kidney abnormalities. The kidney abnormality is
evident histologically on embryonic day 16, shortly after the onset of
metanephric B(2) gene expression, and consists of distorted renal architecture,
foci of tubular dysgenesis, and cyst formation. The dysplastic tubules are of
distal nephron origin [Dolichos biflorus agglutinin (DBA)- and aquaporin-2 (AQP2)
positive, and angiotensinogen negative]. Neonatal antihypertensive therapy fails
to ameliorate the renal abnormalities, arguing against the possibility that the
nephropathy is a consequence of early hypertension. Moreover, the nephropathy is
intrinsic to the embryo, because B(2) homozygous offspring from heterozygous
parents exhibit the same renal phenotype as offspring from homozygous null
parents. Further characterization of the renal phenotype revealed an important
genetic background effect since the penetrance of the congenital nephropathy is
increased substantially upon backcrossing of 129/BL6 B(2) mutants to a uniform
C57BL/6J. We conclude that the type 2 bradykinin receptor is required for the
maintenance of metanephric structure and epithelial integrity in the presence of
fetal stress. This study provides a "proof-of-principle" that defined gene
environment interactions are a cause of congenital renal disease.
PMID- 11015608
TI - Differential effects of dystrophin and utrophin gene transfer in immunocompetent
muscular dystrophy (mdx) mice.
AB - Duchenne muscular dystrophy (DMD) is a fatal disease caused by defects in the
gene encoding dystrophin. Dystrophin is a cytoskeletal protein, which together
with its associated protein complex, helps to protect the sarcolemma from
mechanical stresses associated with muscle contraction. Gene therapy efforts
aimed at supplying a normal dystrophin gene to DMD muscles could be hampered by
host immune system recognition of dystrophin as a "foreign" protein. In contrast,
a closely related protein called utrophin is not foreign to DMD patients and is
able to compensate for dystrophin deficiency when overexpressed throughout
development in transgenic mice. However, the issue of which of the two candidate
molecules is superior for DMD therapy has remained an open question. In this
study, dystrophin and utrophin gene transfer effects on dystrophic muscle
function were directly compared in the murine (mdx) model of DMD using E1/E3
deleted adenovirus vectors containing either a dystrophin (AdV-Dys) or a utrophin
(AdV-Utr) transgene. In immunologically immature neonatal animals, AdV-Dys and
AdV-Utr improved tibialis anterior muscle histopathology, force-generating
capacity, and the ability to resist injury caused by high-stress contractions to
an equivalent degree. By contrast, only AdV-Utr was able to achieve significant
improvement in force generation and the ability to resist stress-induced injury
in the soleus muscle of immunocompetent mature mdx animals. In addition, in
mature mdx mice, there was significantly greater transgene persistence and
reduced inflammation with utrophin compared to dystrophin gene transfer. We
conclude that dystrophin and utrophin are largely equivalent in their intrinsic
abilities to prevent the development of muscle necrosis and weakness when
expressed in neonatal mdx animals with an immature immune system. However,
because immunity against dystrophin places an important limitation on the
efficacy of dystrophin gene replacement in an immunocompetent mature host, the
use of utrophin as an alternative to dystrophin gene transfer in this setting
appears to offer a significant therapeutic advantage.
PMID- 11015609
TI - Microsatellite marker panels for use in high-throughput genotyping of mouse
crosses.
AB - Several microsatellite genotyping panel sets have been developed that are
polymorphic between C57BL/6J and CAST/Ei mice, or C57BL/6J and DBA/2J. One set of
markers for each strain pair has an intermarker distance of approximately 20 cM,
and a second set has an intermarker distance of 5 cM. The 20-cM set contains 105
markers for C57BL/6J x DBA/2J and 108 for C57BL/6J x CAST/Ei, divided into 13
panels. Each 5-cM set includes 350 markers arranged into 45 panels. A panel
contains a number of primer pairs whose fluorescently labeled PCR products can be
pooled together and separated on one lane of a polyacrylamide gel. The sets are
arranged by the size of the PCR product and by the type of fluorescent dye; 5-cM
sets are also arranged by chromosomal region. The 20-cM sets are most useful for
full-genome scans, the 5-cM sets are useful for full-genome and/or for region
specific chromosome screens. Both sets were proven as useful tools for speed
congenic development, quantitative trait loci (QTL) analysis and physical
mapping. These panel sets provide a throughput of 1,536-2,304 mouse genotypes
daily per one gel-based system. Whole genome scans of one animal require 13 or 48
gel lanes, with 20 cM or 5 cM density, respectively.
PMID- 11015610
TI - Gene expression in hypothalamus and brown adipose tissue of mice divergently
selected for heat loss.
AB - Gene expression was evaluated in mice divergently selected for 16 generations for
heat loss, measured by direct calorimetry. The high (MH) heat loss line has
approximately 50% greater heat loss, approximately 35% less body fat,
approximately 20% greater feed intake, and twofold greater activity levels than
the low (ML) heat loss line. At 11 wk, inbred males (developed from MH and ML)
were euthanized 3 h after dark for dissection of tissues and extraction of RNA.
Differential display PCR (DD-PCR) was used to evaluate transcriptional
differences between lines in hypothalamus and brown adipose tissue (BAT).
Evaluation was replicated within and across lines, using family pools of mRNA.
Two genes were confirmed by competitive RT-PCR and/or Northern analysis to have
greater levels of mRNA present in ML relative to MH mice. In both hypothalamus
and BAT, the ribosomal protein L3 (RPL3) gene was expressed at higher levels in
ML, whereas an unknown expressed sequence tag (EST) was also found at higher
levels in the hypothalamus of ML mice. These results implicate RPL3 in regulation
of energy balance and extend the genetic dissection of response to selection to
the transcriptional level.
PMID- 11015611
TI - Transcriptional regulation of the adipocyte fatty acid synthase gene by agouti:
interaction with insulin.
AB - Mice carrying dominant mutations at the agouti locus exhibit ectopic expression
of agouti gene transcripts, obesity, and type II diabetes through unknown
mechanisms. To gain insight into the role of agouti protein in modulating
adiposity, we investigated regulation of a key lipogenic gene, fatty acid
synthase (FAS) by agouti alone and in combination with insulin. Both agouti and
insulin increase FAS activity in 3T3-L1 and in human adipocytes. Agouti and
insulin independently and additively increase FAS activity in 3T3-L1 adipocytes.
We further investigated the mechanism responsible for the agouti-induced FAS
expression in these cells and demonstrated that both insulin (3-fold increase)
and agouti (2-fold) increased FAS gene expression at the transcriptional level.
Furthermore, insulin and agouti together exerted additive effects (5-fold
increase) on FAS gene transcription. Transfection assays of FAS promoter
luciferase fusion gene constructs into 3T3-L1 adipocytes indicated that the
agouti response element(s) is (are) located in the -435 to -415 region (-435/
415) of the FAS promoter. Nuclear proteins binding to this novel sequence are
adipocyte specific. Thus the agouti response sequences mapped to a region
upstream of the insulin-responsive element (which we previously reported to be
located at -67/-52), consistent with additive effects of these two factors on FAS
gene transcription.
PMID- 11015612
TI - Mechanical culture conditions effect gene expression: gravity-induced changes on
the space shuttle.
AB - Three-dimensional suspension culture is a gravity-limited phenomenon. The
balancing forces necessary to keep the aggregates in suspension increase directly
with aggregate size. This leads to a self-propagating cycle of cell damage by
balancing forces. Cell culture in microgravity avoids this trade-off. We
determined which genes mediate three-dimensional culture of cell and tissue
aggregates in the low-shear stress, low-turbulent environment of actual
microgravity. Primary cultures of human renal cortical cells were flown on the
space shuttle. Cells grown in microgravity and ground-based controls were grown
for 6 days and fixed. RNA was extracted, and automated gene array analysis of the
expression of 10, 000 genes was performed. A select group of genes were regulated
in microgravity. These 1,632 genes were independent of known shear stress
response element-dependent genes and heat shock proteins. Specific transcription
factors underwent large changes in microgravity including the Wilms' tumor zinc
finger protein, and the vitamin D receptor. A specific group of genes, under the
control of defined transcription factors, mediate three-dimensional suspension
culture under microgravity conditions.
PMID- 11015613
TI - Large-scale analysis of gene expression changes during acute and chronic exposure
to [Delta]9-THC in rats.
AB - Large-scale cDNA microarrays were employed to assess transient changes in gene
expression levels following acute and chronic exposure to cannabinoids in rats. A
total of 24,456 cDNA clones were randomly selected from a rat brain cDNA library,
amplified by PCR, and arrayed at high density to investigate differential gene
expression profiles following acute (24 h), intermediate (7 days), and chronic
(21 days) exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the
psychoactive ingredient of marijuana. Hippocampal mRNA probes labeled with (33)P
obtained from both vehicle and Delta(9)-THC-treated animals were hybridized with
identical cDNA microarrays. Results revealed a total of 49 different genes
altered by Delta(9)-THC exposure; of these, 28 were identified, 10 had homologies
to expressed sequence tags (ESTs), and 11 had no homology to known sequences in
the GenBank database. Chronic or acute cannabinoid receptor activation altered
expression of several genes (i.e., prostaglandin D synthase, calmodulin) involved
in biochemical cascades of cannabinoid synthesis or cannabinoid effector systems.
Other genes [i.e., neural cell adhesion molecule (NCAM), myelin basic protein],
whose relation to cannabinoid system function was not immediately obvious, were
also significantly altered. Verification of the changes obtained with the large
scale screen was determined by RNA dot blots in different groups of animals
treated the same as those in the large-scale screen. Results are discussed in
terms of the different types of genes affected at different times during chronic
Delta(9)-THC exposure.
PMID- 11015614
TI - Proteoglycans in the developing brain: new conceptual insights for old proteins.
AB - Proteoglycans are a heterogeneous class of proteins bearing sulfated
glycosaminoglycans. Some of the proteoglycans have distinct core protein
structures, and others display similarities and thus may be grouped into families
such as the syndecans, the glypicans, or the hyalectans (or lecticans).
Proteoglycans can be found in almost all tissues being present in the
extracellular matrix, on cellular surfaces, or in intracellular granules. In
recent years, brain proteoglycans have attracted growing interest due to their
highly regulated spatiotemporal expression during nervous system development and
maturation. There is increasing evidence that different proteoglycans act as
regulators of cell migration, axonal pathfinding, synaptogenesis, and structural
plasticity. This review summarizes the most recent data on structures and
functions of brain proteoglycans and focuses on new physiological concepts for
their potential roles in the developing central nervous system.
PMID- 11015615
TI - Structure, function, and control of phosphoinositide-specific phospholipase C.
AB - Phosphoinositide-specific phospholipase C (PLC) subtypes beta, gamma, and delta
comprise a related group of multidomain phosphodiesterases that cleave the polar
head groups from inositol lipids. Activated by all classes of cell surface
receptor, these enzymes generate the ubiquitous second messengers inositol 1,4, 5
trisphosphate and diacylglycerol. The last 5 years have seen remarkable advances
in our understanding of the molecular and biological facets of PLCs. New insights
into their multidomain arrangement and catalytic mechanism have been gained from
crystallographic studies of PLC-delta(1), while new modes of controlling PLC
activity have been uncovered in cellular studies. Most notable is the realization
that PLC-beta, -gamma, and -delta isoforms act in concert, each contributing to a
specific aspect of the cellular response. Clues to their true biological roles
were also obtained. Long assumed to function broadly in calcium-regulated
processes, genetic studies in yeast, slime molds, plants, flies, and mammals
point to specific and conditional roles for each PLC isoform in cell signaling
and development. In this review we consider each subtype of PLC in organisms
ranging from yeast to mammals and discuss their molecular regulation and
biological function.
PMID- 11015616
TI - Role of nitric oxide in the pathogenesis of chronic pulmonary hypertension.
AB - Chronic pulmonary hypertension is a serious complication of a number of chronic
lung and heart diseases. In addition to vasoconstriction, its pathogenesis
includes injury to the peripheral pulmonary arteries leading to their structural
remodeling. Increased pulmonary vascular synthesis of an endogenous vasodilator,
nitric oxide (NO), opposes excessive increases of intravascular pressure during
acute pulmonary vasoconstriction and chronic pulmonary hypertension, although
evidence for reduced NO activity in pulmonary hypertension has also been
presented. NO can modulate the degree of vascular injury and subsequent
fibroproduction, which both underlie the development of chronic pulmonary
hypertension. On one hand, NO can interrupt vascular wall injury by oxygen
radicals produced in increased amounts in pulmonary hypertension. NO can also
inhibit pulmonary vascular smooth muscle and fibroblast proliferative response to
the injury. On the other hand, NO may combine with oxygen radicals to yield
peroxynitrite and other related, highly reactive compounds. The oxidants formed
in this manner may exert cytotoxic and collagenolytic effects and, therefore,
promote the process of reparative vascular remodeling. The balance between the
protective and adverse effects of NO is determined by the relative amounts of NO
and reactive oxygen species. We speculate that this balance may be shifted toward
more severe injury especially during exacerbations of chronic diseases associated
with pulmonary hypertension. Targeting these adverse effects of NO-derived
radicals on vascular structure represents a potential novel therapeutic approach
to pulmonary hypertension in chronic lung diseases.
PMID- 11015617
TI - Proximal tubular phosphate reabsorption: molecular mechanisms.
AB - Renal proximal tubular reabsorption of P(i) is a key element in overall P(i)
homeostasis, and it involves a secondary active P(i) transport mechanism. Among
the molecularly identified sodium-phosphate (Na/P(i)) cotransport systems a brush
border membrane type IIa Na-P(i) cotransporter is the key player in proximal
tubular P(i) reabsorption. Physiological and pathophysiological alterations in
renal P(i) reabsorption are related to altered brush-border membrane
expression/content of the type IIa Na-P(i) cotransporter. Complex membrane
retrieval/insertion mechanisms are involved in modulating transporter content in
the brush-border membrane. In a tissue culture model (OK cells) expressing
intrinsically the type IIa Na-P(i) cotransporter, the cellular cascades involved
in "physiological/pathophysiological" control of P(i) reabsorption have been
explored. As this cell model offers a "proximal tubular" environment, it is
useful for characterization (in heterologous expression studies) of the
cellular/molecular requirements for transport regulation. Finally, the oocyte
expression system has permitted a thorough characterization of the transport
characteristics and of structure/function relationships. Thus the cloning of the
type IIa Na-P(i )cotransporter (in 1993) provided the tools to study renal brush
border membrane Na-P(i) cotransport function/regulation at the cellular/molecular
level as well as at the organ level and led to an understanding of cellular
mechanisms involved in control of proximal tubular P(i) handling and, thus, of
overall P(i) homeostasis.
PMID- 11015618
TI - Dynamics and consequences of potassium shifts in skeletal muscle and heart during
exercise.
AB - Since it became clear that K(+) shifts with exercise are extensive and can cause
more than a doubling of the extracellular [K(+)] ([K(+)](s)) as reviewed here, it
has been suggested that these shifts may cause fatigue through the effect on
muscle excitability and action potentials (AP). The cause of the K(+) shifts is a
transient or long-lasting mismatch between outward repolarizing K(+) currents and
K(+) influx carried by the Na(+)-K(+) pump. Several factors modify the effect of
raised [K(+)](s) during exercise on membrane potential (E(m)) and force
production. 1) Membrane conductance to K(+) is variable and controlled by various
K(+) channels. Low relative K(+) conductance will reduce the contribution of
[K(+)](s) to the E(m). In addition, high Cl(-) conductance may stabilize the E(m)
during brief periods of large K(+) shifts. 2) The Na(+)-K(+) pump contributes
with a hyperpolarizing current. 3) Cell swelling accompanies muscle contractions
especially in fast-twitch muscle, although little in the heart. This will
contribute considerably to the lowering of intracellular [K(+)] ([K(+)](c)) and
will attenuate the exercise-induced rise of intracellular [Na(+)] ([Na(+)](c)).
4) The rise of [Na(+)](c) is sufficient to activate the Na(+)-K(+) pump to
completely compensate increased K(+) release in the heart, yet not in skeletal
muscle. In skeletal muscle there is strong evidence for control of pump activity
not only through hormones, but through a hitherto unidentified mechanism. 5)
Ionic shifts within the skeletal muscle t tubules and in the heart in
extracellular clefts may markedly affect excitation-contraction coupling. 6) Age
and state of training together with nutritional state modify muscle K(+) content
and the abundance of Na(+)-K(+) pumps. We conclude that despite modifying factors
coming into play during muscle activity, the K(+) shifts with high-intensity
exercise may contribute substantially to fatigue in skeletal muscle, whereas in
the heart, except during ischemia, the K(+) balance is controlled much more
effectively.
PMID- 11015619
TI - Calcineurin: form and function.
AB - Calcineurin is a eukaryotic Ca(2+)- and calmodulin-dependent serine/threonine
protein phosphatase. It is a heterodimeric protein consisting of a catalytic
subunit calcineurin A, which contains an active site dinuclear metal center, and
a tightly associated, myristoylated, Ca(2+)-binding subunit, calcineurin B. The
primary sequence of both subunits and heterodimeric quaternary structure is
highly conserved from yeast to mammals. As a serine/threonine protein
phosphatase, calcineurin participates in a number of cellular processes and
Ca(2+)-dependent signal transduction pathways. Calcineurin is potently inhibited
by immunosuppressant drugs, cyclosporin A and FK506, in the presence of their
respective cytoplasmic immunophilin proteins, cyclophilin and FK506-binding
protein. Many studies have used these immunosuppressant drugs and/or modern
genetic techniques to disrupt calcineurin in model organisms such as yeast,
filamentous fungi, plants, vertebrates, and mammals to explore its biological
function. Recent advances regarding calcineurin structure include the
determination of its three-dimensional structure. In addition, biochemical and
spectroscopic studies are beginning to unravel aspects of the mechanism of
phosphate ester hydrolysis including the importance of the dinuclear metal ion
cofactor and metal ion redox chemistry, studies which may lead to new calcineurin
inhibitors. This review provides a comprehensive examination of the biological
roles of calcineurin and reviews aspects related to its structure and catalytic
mechanism.
PMID- 11015620
TI - Prolactin: structure, function, and regulation of secretion.
AB - Prolactin is a protein hormone of the anterior pituitary gland that was
originally named for its ability to promote lactation in response to the suckling
stimulus of hungry young mammals. We now know that prolactin is not as simple as
originally described. Indeed, chemically, prolactin appears in a multiplicity of
posttranslational forms ranging from size variants to chemical modifications such
as phosphorylation or glycosylation. It is not only synthesized in the pituitary
gland, as originally described, but also within the central nervous system, the
immune system, the uterus and its associated tissues of conception, and even the
mammary gland itself. Moreover, its biological actions are not limited solely to
reproduction because it has been shown to control a variety of behaviors and even
play a role in homeostasis. Prolactin-releasing stimuli not only include the
nursing stimulus, but light, audition, olfaction, and stress can serve a
stimulatory role. Finally, although it is well known that dopamine of
hypothalamic origin provides inhibitory control over the secretion of prolactin,
other factors within the brain, pituitary gland, and peripheral organs have been
shown to inhibit or stimulate prolactin secretion as well. It is the purpose of
this review to provide a comprehensive survey of our current understanding of
prolactin's function and its regulation and to expose some of the controversies
still existing.
PMID- 11015621
TI - Development of intestinal transport function in mammals.
AB - Considerable progress has been made over the last decade in the understanding of
mechanisms responsible for the ontogenetic changes of mammalian intestine. This
review presents the current knowledge about the development of intestinal
transport function in the context of intestinal mucosa ontogeny. The review
predominantly focuses on signals that trigger and/or modulate the developmental
changes of intestinal transport. After an overview of the proliferation and
differentiation of intestinal mucosa, data about the bidirectional traffic
(absorption and secretion) across the developing intestinal epithelium are
presented. The largest part of the review is devoted to the description of
developmental patterns concerning the absorption of nutrients, ions, water,
vitamins, trace elements, and milk-borne biologically active substances.
Furthermore, the review examines the development of intestinal secretion that has
a variety of functions including maintenance of the fluidity of the intestinal
content, lubrication of mucosal surface, and mucosal protection. The age
dependent shifts of absorption and secretion are the subject of integrated
regulatory mechanisms, and hence, the input of hormonal, nervous, immune, and
dietary signals is reviewed. Finally, the utilization of energy for transport
processes in the developing intestine is highlighted, and the interactions
between various sources of energy are discussed. The review ends with suggestions
concerning possible directions of future research.
PMID- 11015622
TI - Role of platelet-activating factor in cardiovascular pathophysiology.
AB - Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a
family of biologically active, structurally related alkyl phosphoglycerides. PAF
acts via a specific receptor that is coupled with a G protein, which activates a
phosphatidylinositol-specific phospholipase C. In this review we focus on the
aspects that are more relevant for the cell biology of the cardiovascular system.
The in vitro studies provided evidence for a role of PAF both as intercellular
and intracellular messenger involved in cell-to-cell communication. In the
cardiovascular system, PAF may have a role in embryogenesis because it stimulates
endothelial cell migration and angiogenesis and may affect cardiac function
because it exhibits mechanical and electrophysiological actions on
cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure
mainly by affecting the renal vascular circulation. In pathological conditions,
PAF has been involved in the hypotension and cardiac dysfunctions occurring in
various cardiovascular stress situations such as cardiac anaphylaxis and
hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental
studies indicate that PAF has a critical role in the development of myocardial
ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of
leukocytes in inflamed tissue by promoting adhesion to the endothelium and
extravascular transmigration of leukocytes. The finding that human heart can
produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic
action of PAF suggests that this mediator may have a role also in human
cardiovascular pathophysiology.
PMID- 11015623
TI - Emotional state, coping styles, and somatic variables in patients with chronic
hepatitis C.
AB - The authors in a cross-sectional study examined 113 patients with chronic
hepatitis C (CHC) without widely progressed or decompensated liver disease. The
patients were investigated for emotional state (depression, anxiety, coping
styles) and somatic/sociodemographic variables. A high percentage of patients had
positive scores for depression (22.4%) and anxiety (15.2%). Mode of acquisition
(e.g., former drug abuse) and histological grade of liver damage had no
significant influence on emotional state or coping strategies. Older patients (>
or = 50 years) were significantly more depressed (P = 0.024). Patients with a
recently diagnosed CHC (> 4 weeks, < 6 months) had significantly lower scores for
depression (P = 0.003) and anxiety (P = 0.001) than the subgroup with a time
interval since initial diagnosis of more than 5 years. Recently diagnosed CHC
patients also showed the highest levels of problem-solving behavior. Patients who
were advised not to undergo an interferon therapy were significantly more
depressed (P = 0.001) and anxious (P = 0.028). Older patients with CHC and
patients with a long period since CHC diagnosis or who were advised not to
undergo interferon therapy should be carefully and regularly assessed for
depression, anxiety, and inappropriate coping styles.
PMID- 11015624
TI - An observer scale to measure alexithymia.
AB - The authors developed a relatively brief observer alexithymia measure that can be
used by patients' acquaintances and relatives. Items corresponding to the
defining features of alexithymia (California Q-Set Alexithymia Prototype) were
written, and the new instrument's psychometric properties were evaluated in 3 lay
rater samples. The 33-item Observer Alexithymia Scale (OAS) is internally
consistent (coefficient alphas = 0.88 and 0.89) and stable (2-week test-retest
reliability = 0.87). Moreover, it has an interpretable five-factor structure
(based on exploratory and confirmatory factor analyses): distant, uninsightful,
somatizing, humorless, and rigid. The OAS is a reliable instrument with a stable
factor structure and good conceptual coverage and thus, it appears to be a useful
tool for collecting observer data on the clinically relevant expressions of
alexithymia that receive minimal attention.
PMID- 11015625
TI - The Structured Interview for Renal Transplantation--SIRT.
AB - Despite the fact that the demand for psychiatric evaluations of organ transplant
recipients is increasing, there is not a commonly agreed upon protocol that can
guide clinicians. A standard psychiatric interview, although necessary, is not
sufficient when interviewing transplant candidates. In addition, it is important
to acquire information specific to the medical regimen associated with renal
disease and renal transplantation. The purpose of this paper is to present the
Structured Interview for Renal Transplantation (SIRT). The SIRT was developed as
a tool to guide clinicians through the interview process by providing a
comprehensive structure while still allowing for flexibility. There are many
advantages of using the SIRT--it is a tool that facilitates a clinician's ability
to conduct a thorough evaluation in a time-efficient manner. It is also an
excellent instrument for training clinicians, and the structure of the interview
is appropriate for use in research.
PMID- 11015626
TI - Religious altruism and organ donation.
AB - Clinicians performing psychiatric assessments of potential organ donors must
consider the motivations behind an act that is--strictly in terms of its
physiological implications--entirely altruistic. The authors present two case
reports in which proposed kidney donors conceptualized their offers exclusively
in terms of their religious beliefs and not in terms of kinship or emotional
intimacy with the intended recipients. The negative reactions of some clinicians
to the offers reveal the readiness with which religious beliefs can be
pathologized and the way in which biological relationships can unduly restrict
the clinical understanding of healthy altruism.
PMID- 11015628
TI - Dimensions of psychopathology in the medically ill. A latent trait analysis.
AB - The authors examined the latent structure of psychiatric symptoms occurring in
patients with medical illness. Symptom data were collected from 312 hospitalized
medically ill patients using the Monash Interview for Liaison Psychiatry and
subjected to latent trait analysis. A model with 5 dimensions provided an
acceptable fit to the data. Dimensions were characterized as demoralization,
anhedonia, autonomic anxiety, somatic symptoms, and grief. The demoralization
dimension was similar to the concept of demoralization described by Frank and to
the "giving up-given up complex" described by Engel. The concepts of
demoralization, grief, and anhedonia may be useful in increasing understanding of
the minor depressions in people with medical illness and in increasing the
specificity of psychological and pharmacological treatments for these disorders.
PMID- 11015627
TI - Psychiatric training in primary care medicine residency programs. A national
survey.
AB - The authors conducted a national survey to investigate the current status of
psychiatric training in primary care/internal medicine residencies. Fifty-four
residency training directors completed and returned the survey. The survey
results show that an average of 99 hours (69.5 hours clinical plus 29.8 hours
didactics) is devoted to psychiatric training during the 3 years of primary
care/internal medicine residency training. Responding residency training
directors indicated that psychiatric training is important (an average of 7 out
of 10 on a 10-point rating scale), and 63% of respondents indicated that more
training in psychiatry is needed.
PMID- 11015630
TI - The use of a transitional object in the context of medical illness.
PMID- 11015629
TI - Association between depressive symptoms and mortality in medical inpatients.
AB - The authors interviewed a consecutive series of medical inpatients (N = 241)
using the Schedule for Affective Disorders and Schizophrenia to determine which
depressive symptoms are associated with in-hospital mortality. Fifteen depressive
symptoms, pain, and physical discomfort were assessed along with medical
comorbidity. Twenty patients died in-hospital (8.3%). Logistic regression showed
that anhedonia, hopelessness, worthlessness, indecisiveness, and insomnia
predicted in-hospital death after adjusting for physical comorbidity and age.
Clinicians should be aware that these depressive symptoms may predict mortality
in medical inpatients. Future studies should address which treatment modalities
lead to better outcomes.
PMID- 11015631
TI - Seizure disorder is in the differential diagnosis of panic disorder.
PMID- 11015632
TI - Prophylactic treatment of depression induced by interferon-alpha.
PMID- 11015633
TI - Breast cancer, bipolar disorder, catatonia, and life-preserving electroconvulsive
therapy.
PMID- 11015634
TI - Steroid-induced mania in poststroke patient involving the right basal ganglion
and right frontal region.
PMID- 11015635
TI - Delusional parasitosis accompanied by word deafness due to cerebral infarction:
folie a deux.
PMID- 11015636
TI - Severe and moderate hypertriglyceridemia secondary to citalopram and fluoxetine.
PMID- 11015637
TI - Diagnosing demoralization in consultation psychiatry.
PMID- 11015638
TI - Illusion or hallucination? Cholecystitis presenting as pseudopregnancy in
schizophrenia.
PMID- 11015639
TI - Hepatotoxicity with combination of valproic acid, ritonavir, and nevirapine: a
case report.
PMID- 11015641
TI - Intravenous valproate treatment of severe manic symptoms after gastric bypass
surgery: a case report.
PMID- 11015640
TI - Neuroleptic malignant syndrome associated with use of risperidone, ritonavir, and
indinavir: a case report.
PMID- 11015642
TI - [XVIII Congress of the French Society of Endocrinology. 4-7 October 2000. Brest,
France. Abstracts].
PMID- 11015643
TI - [On the guidelines concerning correct anatomic pathology and cytopathology
practice by the Union of Belgian Pathologists of Medical Specialties and
Pathologic Anatomy].
PMID- 11015644
TI - [Emergence of new infectious disease: the microbiologist's point of view].
PMID- 11015645
TI - [Emergence of new infectious disease: the anatomic pathologists's point of view].
PMID- 11015646
TI - [Clear cell soft tissue sarcoma. Clinical, histopathological and prognostic study
of 36 cases].
AB - Thirty six cases of clear cell sarcoma of soft tissue are reported. The median
age was 44 years (5 to 80 years). The principal sites were the foot (11 cases),
the hand and wrist (7 cases) and the knee (6 cases). The architecture was
fascicular with lobular arrangement of cells delimited by delicate fibrous septa
intimately bound to tendons or aponeuroses. Tumoral cells were round or fusiform
with abundant clear cytoplasm sometimes epithelioid with round nuclei and
prominent nucleoli. The mitotic rate was evaluated to 9/10 HPF. S100 protein was
expressed in 33/36 cases and HMB45 marked 29/31 cases, without expression of
cytokeratin. Three-year and 5-year survival rate were respectively 72% and 62%.
Prognosis factors for global survival were efficiency of initial treatment with
distal location and necrosis and FNCLCC grade. The distinction of clear cell
sarcoma from metastatic melanoma is important because of the difference of
prognosis.
PMID- 11015647
TI - [Evaluation of the effect of pathology slide review on clinical practice in an
oncology center].
AB - Our aim was to evaluate the clinical impact of pathology review in an oncology
center, in which review is not performed for every patient. This retrospective
study involved 100 consecutive patients, whose slides were reviewed in our
center. A standardized data sheet was filled out by oncologists for each patient.
Pathology review was considered as responsible for a major (35%), moderate (40%),
or mild or no (25%) modification of clinical practice. Modification concerned
either initial investigations, treatment or medical follow up, and was
independent of the reason for which review was performed. Eleven patients
underwent a second biopsy. Whatever the possible discrepancies between initial
and review diagnosis, our results show that pathological review has a major
influence on clinical practice in patients with cancer.
PMID- 11015648
TI - [Lichen striatus: evaluation of histologic criteria in 13 cases].
AB - Lichen striatus (LS) is an uncommon dermatosis that generally affects children.
Sometimes biopsy is required to assess the diagnosis. It is usually mentioned
that LS has no specific histopathological criteria. Recently Gianotti et al., in
50% of the examined cases, found clues to the diagnosis. We have evaluated 13
biopsies of children affected by LS, in order to evaluate histopathological
criteria to allow a diagnosis. The features nearly constantly present (12/13) in
each specimen were focally band-like lymphocytic infiltrate with variable
exocytosis and necrotic keratinocytes within the epidermis surrounded by
lymphocytes. Epidermis hyperplasia, sometimes psoriasiform, was also present. In
addition, one of remarkable the features of LS was the alignment of the
infiltrate along eccrine ducts and glands and/or follicles. In 3 cases the deep
lymphocytic infiltration was particularly dense. These results confirm that
helpful clues to histopathological diagnosis of LS exist.
PMID- 11015649
TI - [Roles and mechanisms of apoptosis in infectious diseases].
PMID- 11015650
TI - [Emerging infectious diseases].
PMID- 11015651
TI - [Disseminated mucormycosis in AIDS].
AB - Mucormycosis is a rare often fatal opportunistic condition. It mainly occurs in
immunocompromised subjects but rarely in AIDS patients. An eighteen-year-old HIV+
man from Zaire died rapidly from disseminated mucormycosis with pulmonary,
cardiac, renal, hepatic, splenic and gastric involvement. Fungi were observed in
all these organs with a particular vascular trophism. Rhizopus orizae was
identified on cultures. Rapid microscopic diagnosis, in the localized stage,
could improve the poor prognosis of this infection.
PMID- 11015652
TI - [Cutaneous nodular infection with hemopathy].
AB - A 36-year-old man with treated hairy cell leukemia developed a skin infection due
to Mycobacterium marinum. A spectrum of atypical cutaneous mycobacteriosis
presentations with immunosuppression can be found. The recognition of the disease
needs cutaneous biopsies for histopathology and its identification by specific
laboratory methods to adapt treatment.
PMID- 11015653
TI - [Endolymphatic sac tumor: a rare tumor of internal ear. Report of two cases].
AB - Papillary tumors of the temporal bone are rare and aggressive neoplasms. Recently
described, these tumors had initially a presumed middle-ear origin. Only
recently, convincing anatomic, morphological and immunohistochemical arguments
exist for an endolymphatic sac origin (inner-ear origin). We report two cases of
endolymphatic sac tumor. These tumors can be encountered sporadically or in Von
Hippel-Lindau disease. They classically grow very slowly, resulting in late
clinical manifestations with expansive mass invading temporal bone and extending
in posterior fossa. Radiologically, these endolymphatic sac tumors can mimic
metastatic carcinoma, paraganglioma, or cerebellar haemangioblastoma specially in
von Hippel-Lindau disease. Histology shows a papillary epithelial tumor with
hypervascular stroma, without atypia. The treatment for these tumors is surgical
and curative when early diagnosed. In apparently sporadic cases, genetic analysis
for Von Hippel-Lindau disease should be considered.
PMID- 11015654
TI - [A case of primitive meningeal rhabdomyosarcoma. Histological,
immunohistochemical and ultrastructural study].
AB - A 64 year-old patient, complained of headache and neurological disorders. CT scan
found a voluminous solitary tumor of the posterior part of the left cavernous
sinus. Removal of tumor was followed by a rapid recurrence and by the patient's
death. Histologic study found a malignant undifferentiated tumoral proliferation,
with strap-like cells. Immunohistochemical stains were positive for conjunctival
and muscular differentiation. Ultrastructural study revealed intracytoplasmic
filamentous striated structure. The primary meningeal rhabdomyosarcoma is an
exceptional tumor, generally affecting young patients. Its prognosis is poor and
its histogenesis remains unclear.
PMID- 11015655
TI - [Primary large cell neuroendocrine carcinoma of the kidney: morphologic and
immunohistochemical features of two cases].
AB - Primary neuroendocrine carcinomas of the kidney are infrequent. The large cell
neuroendocrine carcinoma is a subtype with an aggressive course and a worse
prognosis. We report two cases, a 35-year-old man and a 75-year-old woman who
died within 6 and 5-months after surgery despite radical nephrectomy and
chemotherapy. Histological and immunohistochemical features are presented.
PMID- 11015656
TI - [Intraluminal renal metastasis from a rectal adenocarcinoma: an unusual site].
AB - Primary adenocarcinoma of the urinary tract are uncommon. But secondary
involvement of pyelocalyceal system by metastasis of colorectal origin is rare.
We report a case of late rectal metastasis with renal pelvis growth presenting as
a pyonephrosis. This study emphasizes the relevance of cytokeratin 7 and 20
immunostaining in such differential diagnosis.
PMID- 11015657
TI - [Adenomyoepithelioma of the breast: two cases].
AB - Adenomyoepithelioma of the breast are very rare and form a heterogeneous tumoral
group in terms of their morphology and biological behaviour. We report two
adenomyoepitheliomas of the breast. One appeared in a 29-year-old woman and was a
tubular adenomyoepithelioma. The patient was free of disease at a 22 months
follow-up. The other was a lobular adenomyoepithelioma that appeared in a 76-year
old woman and was characterized by its high mitotic rate and its association with
myoepitheliosis. Adenomyoepitheliomas of the breast are currently classified as
low grade malignant tumors that may recur and rarely metastasize, but their
histoprognostic factors are not yet defined.
PMID- 11015658
TI - [Adenomatoid tumor of the pleura. Case report].
AB - We report a case of an adenomatoid tumor of particular location within the
pleura, incidentally discovered on a pulmonary lobectomy specimen after surgical
resection of a pulmonary squamous cell carcinoma. This adenomatoid tumor appeared
as a unique pleural mass located away from the primary carcinoma and consisted of
a cellular proliferation organised in tubes and sheets. Adenomatoid tumors are
considered as benign tumors of mesothelial nature. Their morphological and
immunohistochemical features in association with their location to the pleura,
warrant a precise analysis to eliminate malignant tumours such as malignant
mesothelioma or metastatic adenocarcinoma.
PMID- 11015659
TI - [A case study of Woringer-Kolopp disease. Immunohistochemical study].
AB - Woringer-Kolopp disease is a localized epidermotropic T cell lymphoma with good
prognosis. We describe a 79-year-old man with an erythematous scaly plaque of the
foot. Clinical diagnosis of psoriasis, parapsoriasis and fungal infection were
proposed. Histopathological and immunohistochemical findings were characteristic
of Woringer-Kolopp disease. We observed an immunohistochemical positivity of
tumour cells for the anti-CD103 antibody (alphaEB7 integrin) according to the
epidermotropism of this localized cutaneous T cell lymphoma.
PMID- 11015660
TI - [Tender nodule of the right hand. What is your diagnosis? Diagnosis: Intra
vascular nodular fasciitis].
PMID- 11015661
TI - [A tumoral pitfall. What is your diagnosis? Diagnosis: Chordoid meningioma].
PMID- 11015662
TI - [An uncommon mastoid cyst. What is your diagnosis? Diagnosis: ceruminous cystic
adenoma].
PMID- 11015663
TI - [An ulcerative tumor of the fundic mucosa. What is your diagnosis? Diagnosis:
Gastric plasma cell granuloma].
PMID- 11015664
TI - [An acid rectal polyp. What is your diagnosis? Diagnosis: Gastric heterotopia of
the rectum].
PMID- 11015665
TI - [A standardised histopathological worksheet for the histopathologic examination
of primary cutaneous melanomas. Experiences at the Gustave-Roussy Institute].
AB - A standardised worksheet for the histopathology report of primary cutaneous
melanoma used at the Gustave-Roussy Institute is described. Each item is
discussed.
PMID- 11015666
TI - [A proposal for a method of reporting cervico-uterine smears].
AB - A method for reporting Papsmears is proposed. Paperwork is limited to choosing a
few codes on a working list prepared according to the Bethesda system and the
ADICAP coding system. The method is easy to use. It reduces the work load of time
for cytologists and secretaries. It allows harmonization and structurization of
the look and the filling of reports for Papsmears. It may be easily adapted for
vaginal smears. It leads to a report complete and adapted to the Bethesda system.
It gives the possibility of adding comments and additional codes. It avoids most
mistakes about obligatory codes. It makes easier to perform statistical
evaluation and to initiate a quality control program.
PMID- 11015667
TI - [Recent advance in the classification of tumors using microarrays].
PMID- 11015668
TI - [Metachronous bilateral germ cell tumors of the testis].
PMID- 11015669
TI - [A diagnostic pitfall in the pathology of bladder tumors: the nested variant of
urothelial carcinoma].
PMID- 11015670
TI - [A misleading mistake in the classification of colonic and rectal cancers, in the
4th edition of the TNM Atlas, published in French by Springer].
PMID- 11015671
TI - [Neurofibromatosis type 2. Preliminary results of gamma knife radiosurgery of
vestibular schwannomas].
AB - BACKGROUND AND PURPOSE: The aim of this study was to assess tolerance and
efficacy of gamma knife radiosurgery on vestibular schwannomas for patients
affected with neurofibromatosis type 2. METHODS: Between July 1992 and December
1997, a gamma knife procedure was performed on 35 vestibular schwannomas
affecting 27 patients (12 females and 15 males, mean age=27 years-old, range: 14
65). Fifteen of the patients were included in the Wishart subtype (severe form)
and 12 patients in the Gardner subtype (mild form). This group of 27 patients
represented 8,2% of the total group of vestibular schwannomas radiosurgically
treated by our team. The mean tumor volume was 4,000 mm(3) (range: 400-14,400
mm(3)) and staging according to Koos classification was 9 stage 2 tumors
(extension in the cerebellopontine angle), 19 stage 3 tumors (in contact with the
brain stem or cerebellum) and 7 stage 4 tumors (compression of axial structures).
The delivered mean marginal dose (50% isodose) was 13 Gy (range: 10-18 Gy). After
the treatment, the mean clinical and radiological follow-up was 32 months (range:
6-70). RESULTS: Twenty six (74%) of the treated tumors were controlled by the
treatment (15 stabilizations and 11 regressions of the tumor volume) at last
follow-up. One microsurgical removal was required in a growing stage 4 tumor and
in 2 cases of growing stage 3 tumors. Three post-radiosurgical facial nerve
deficits (9%) were observed, 2 of them were transient. According to the Gardner
and Robertson classification, classes I (good) and II (serviceable) hearing were
preserved at last follow-up in 57% of the patients having the same hearing level
prior to the gamma knife. CONCLUSIONS: Our experience confirms that tolerance of
gamma knife radiosurgery compares favorably with microsurgery of bilateral
vestibular schwannomas. This treatment should be restricted to small and medium
growing tumors. Treatment strategy of neurofibromatosis type 2 patients should be
planned by multidisciplinary experienced teams disposing of the whole
armamentarium. A longer follow-up study is required to confirm the current
results regarding the tumor control rate.
PMID- 11015672
TI - The carpal tunnel syndrome. Anatomo-clinical correlations.
AB - We review a series of 1,280 operated cases of carpal tunnel syndrome (CTS), with
an unexpected high frequency of transverse muscular fibers within the carpal
canal (11%), particularly in a group of young male patients under 30 years of
age. This abnormal presence of muscle fibers could explain the early development
of CTS in young male workers.
PMID- 11015673
TI - [Hearing preservation in vestibular schwannoma surgery: indications, techniques
and results in the literature since 1990].
AB - Many authors have recently reported hearing preservation for approximately two
thirds of acoustic neuroma patients. The results have driven them to recommend
early surgery for all patients whose hearing might be saved. Inversely, other
authors advocate that MRI-screening may be beneficial in some patients and
suggest surgery only in case of tumor growth or progressive hearing loss. In
order to facilitate therapeutic decision making, we reviewed the techniques and
results in the main papers dealing with hearing preservation in the course of
acoustic neuroma surgery published since 1990. This analysis showed that the
average percentage of useful hearing preservation is about 31%. It is however
difficult to compare the different series due to the different methodologies
used. This emphasizes the need for standardization of hearing selection and
reporting criteria to a) identify factors predictive of success (tumor
characteristics, preoperative hearing, monitoring, surgical pathways), and b)
elaborate well accepted decisional guidelines (early surgery or MRI screening),
notably for small and non-symptomatic tumors which show increasing prevalence.
PMID- 11015674
TI - [Apoptosis and pathologies of the central nervous system].
AB - The program of cell death called apoptosis is a biochemical and genetical pathway
which has been well conserved throughout evolution. In the past years, the
involvement of apoptosis has been shown not only during the embryonic development
of the nervous system, but also in neurodegenerative diseases. Moreover,
resistance to apoptosis is clearly an important factor in tumor growth and seems
to be, at least partially, a major process in chemo- and radio-resistance. In
this review, we briefly describe the main molecular events of the apoptotic
process, known to date, and discuss possible defects in the central nervous
system diseases.
PMID- 11015675
TI - [Arachnoid cysts of the middle fossa and associated subdural hematoma. Three case
reports and review of the literature].
AB - BACKGROUND AND PURPOSE: We report 3 cases of subdural hematoma associated with
arachnoid cyst of the middle fossa, and discuss the treatment. METHODS: Three
males aged 33, 63 and 68 were treated in our institution. Before this event the
cyst was asymptomatic and unknown. Magnetic resonance imaging was the most
contributive radiologic exam. Surgical procedure was limited to subdural hematoma
evacuation. The internal wall of subdural hematoma was opened in all cases.
RESULTS: The clinical outcome was good for all patients. The CT or MRI scan
follow-up 3 months later revealed nearly total disappearance of subdural hematoma
for 2 out of 3 cases. For one patient the volume of arachnoid cyst decreased.
CONCLUSIONS: We propose subdural hematoma drainage without any specific treatment
(shunt or fenestration) of the arachnoid cyst, for this category of patient.
PMID- 11015676
TI - [Spontaneous temporo-sphenoidal encephalocele. A case report].
AB - A case of anteromedial temporo-sphenoidal meningo-encephalocele in a 43-year-old
woman is reported. She was referred to us after a five-year history of rhinorrhea
of CSF. Three years ago, she presented an epileptic seizure. CT scan showed an
empty sella and an opacity of the right part of the sphenoid sinus. On coronal
sections, a defect was visible in the superior wall of the right lateral recess
of the sphenoid sinus. The lateral sphenoidal rhinorrhea was confirmed by a CT
cisternography. The patient was operated on via a frontotemporal approach with an
orbitozygomatic removal. The dural defect was filled by a patch of pericranium.
The patient is without evidence of cerebrospinal fluid leak 2.5 years later.
Fifteen cases of anteromedial temporosphenoidal meningo-encephaloceles have been
reported. They probably are of a developmental origin. Some cases have been
successfully treated via a transsphenoidal route. However, surgical failures
related to this approach can be due to the lack of control of the lateral recess
of the sphenoid sinus. Therefore, the frontotemporal approach seems more
adequate.
PMID- 11015677
TI - [Epidural hydatid cyst of the posterior fossa].
AB - We report a case of epidural hydatid cyst in the posterior fossa in a 5-year-old
child. The disease was revealed by raised intracranial pressure with torticollis.
The diagnosis was based on the brain CT scan and MRI, and confirmed surgically.
The course was uneventful. Cranial epidural hydatid cysts are very rare: only 18
cases have been reported previously in the literature.
PMID- 11015678
TI - [Synovial cyst of cervical spine].
AB - The synovial cyst is a rare cause of cervical medullar compression. We report on
one case of a 74-year-old man hospitalized for electric discharge in the limbs at
neck extension. The MRI and CT-scan revealed a posterior extradural cystic lesion
at the level of C5-C6. The surgical excision of the lesion resulted in completed
recovery. The histological examination confirmed the diagnosis of a synovial
cyst. Through this case and the review of the 9 reported cases in the literature,
we discuss the etiopathogenesis, diagnosis and treatment of the lower cervical
synovial cyst.
PMID- 11015679
TI - [Cerebellar hemorrhage complicating a supratentorial craniotomy. A case report
and review of the literature].
AB - Postoperative cerebellar hemorrhage after a supratentorial craniotomy represents
a rare event. We report a case of a patient with a meningioma of the jugum who
developed suddenly after surgery a neurological deterioration due to a cerebellar
hemorrhage detected on the CT scan. An occipital craniectomy and an external
ventricular drainage were performed in emergency. A complete neurological
recovery was observed after surgery. Nineteen similar other cases are found in
the literature. Pre- and postoperative high blood pressure, lowered intracranial
pressure and mispositioning of the head during surgery could be at the origin of
the hemorrhage. Size of the hemorrhage, time between diagnosis and treatment
represent two prognostic factors. All patients, who present a neurological
deterioration in postoperative course, must have CT scan including posterior
fossa.
PMID- 11015680
TI - [Aneurysm of the postero-inferior cerebellar artery associated with arteriovenous
malformation].
AB - A saccular aneurysm of the posterior inferior cerebellar artery lying in the
fourth ventricle and an arteriovenous malformation in the cerebellum fed by the
same artery are reported. Clipping of the neck of the aneurysm and total removal
of the arteriovenous malformation were performed successfully during one stage.
Review of the pertinent literature indicates that the aneurysm of the posterior
inferior cerebellar artery originates from the peripheral portion of the artery
when associated with arteriovenous malformation. The treatment is often surgical
with good results in more than 80% of cases. A one-stage operation is the method
of choice. Embolization is not without risk and can be attempted when the PICA's
course allows easy catheterization.
PMID- 11015681
TI - [Unique intracerebral plasmacytoma: a case possibly induced by head trauma].
PMID- 11015682
TI - [Guidelines for antibiotic prophylaxis in surgery patients: application to
Neurosurgery. 1999 update. Working Group of Experts of the Societe Francaise
d'Anesthesie et de Reanimation (SFAR)].
PMID- 11015683
TI - Transporter-mediated permeation of drugs across the blood-brain barrier.
AB - Drug distribution into the brain is strictly regulated by the presence of the
blood-brain barrier (BBB) that is formed by brain capillary endothelial cells.
Since the endothelial cells are connected to each other by tight junctions and
lack pores and/or fenestrations, compounds must cross the membranes of the cells
to enter the brain from the bloodstream. Therefore, hydrophilic compounds cannot
cross the barrier in the absence of specific mechanisms such as membrane
transporters or endocytosis. So, for efficient supply of hydrophilic nutrients,
the BBB is equipped with membrane transport systems and some of those transporter
proteins have been shown to accept drug molecules and transport them into brain.
In the present review, we describe mainly the transporters that are involved in
drug transfer across the BBB and have been molecularly identified. The transport
systems described include transporters for amino acids, monocarboxylic acids,
organic cations, hexoses, nucleosides, and peptides. Most of these transporters
function in the direction of influx from blood to brain; the presence of efflux
transporters from brain to blood has also been demonstrated, including P
glycoprotein, MRPs, and other unknown transporters. These efflux transporters
seem to be functional for detoxication and/or prevention of nonessential
compounds from entering the brain. Various drugs are transported out of the brain
via such efflux transporters, resulting in the decrease of CNS side effects for
drugs that have pharmacological targets in peripheral tissues or in the reduction
of efficacy in CNS because of the lower delivery by efflux transport. To identify
the transporters functional at the BBB and to examine the possible involvement of
them in drug transports by molecular and physiological approaches will provide a
rational basis for controlling drug distribution to the brain.
PMID- 11015684
TI - Statistical properties of thermodynamic quantities for cyclodextrin complex
formation.
AB - Literature values of DeltaG degrees (change in Gibbs free energy), DeltaH degrees
(change in enthalpy), and TDeltaS degrees (temperature times change in entropy)
for 1:1 complex formation by alpha-, beta-, and gamma-cyclodextrins constitute
normally distributed populations with the following statistical parameters (all
energy quantities in kcal mol(-1); n is the number of data points; mu is the
population mean; sigma is the standard deviation): for alpha-cyclodextrin, n =
512, micro(DeltaG) = -2.85, sigma(DeltaG) = 1.23, micro(DeltaH) = -4.77,
sigma(DeltaH) = 2.98, micro(TDeltaS) = -1.96, and sigma(TDeltaS) = 2.72; for beta
cyclodextrin, n = 415, micro(DeltaG) = -3.67, sigma(DeltaG) = 1. 37,
micro(DeltaH) = -4.24, sigma(DeltaH) = 2.89, micro(DeltaS) = -0. 56, and
sigma(TDeltaS) = 2.63; for gamma-cyclodextrin, n = 42, micro(DeltaG) = -3.71,
sigma(DeltaG) = 1.19, micro(DeltaH) = -3.10, sigma(DeltaH) = 3.39, micro(TDeltaS)
= +0.69, and sigma(TDeltaS) = 3. 29. The temperature is 298.15 K. The mean DeltaG
degrees values correspond to binding constants of 123, 490, and 525 M(-1) for
alpha-, beta-, and gamma-cyclodextrins, respectively.
PMID- 11015685
TI - Intrinsic absolute bioavailability prediction in rats based on in situ absorption
rate constants and/or in vitro partition coefficients: 6-fluoroquinolones.
AB - A preliminary study attempting to predict the intrinsic absolute bioavailability
of a group of antibacterial 6-fluoroquinolones-including true and imperfect
homologues as well as heterologues-was carried out. The intrinsic absolute
bioavailability of the test compounds, F, was assessed on permanently cannulated
conscious rats by comparing the trapezoidal normalized areas under the plasma
concentration-time curves obtained by intravenous and oral routes (n = 8-12). The
high-performance liquid chromatography analytical methods used for plasma samples
are described. Prediction of the absolute bioavailability of the compounds was
based on their intrinsic rat gut in situ absorption rate constant, k(a). The
working equation was: where T represents the mean absorbing time. A T value of
0.93 (+/-0.06) h provides the best correlation between predicted and
experimentally obtained bioavailabilities (F' and F, respectively) when k(a)
values are used (slope a = 1.10; intercept b = -0.05; r = 0.991). The k(a) values
can also be expressed in function of the in vitro partition coefficients, P,
between n-octanol and a phosphate buffer. In this case, theoretical k(a) values
can be determined with the parameters of a standard k(a)/P correlation previously
established for a group of model compounds. When P values are taken instead of
k(a) values, reliable bioavailability predictions can also be made. These and
other relevant features of the method are discussed.
PMID- 11015686
TI - Impact of mechanism-based enzyme inactivation on inhibitor potency: implications
for rational drug discovery.
AB - Mechanism-based enzyme inactivators (MBEIs) have unique kinetic actions that make
predictions of potency, selectivity, and potential for metabolic drug
interactions more complex than for competitive antagonists. We have derived a
mathematical relationship that links the influence of substrate concentration and
binding constant ([S] and K(m), respectively), inhibitor concentration and
binding constant ([I] and K(I), respectively), and inactivation rate constant
(k(inact)) to enzyme activity (v) and maximal activity (V(max)) at any time (t).
The kinetic behavior of this relationship was validated in murine-macrophage cell
cultures using MBEIs of nitric oxide synthase (NOS). This initial equation was
also used in the derivation of a new relationship that directly links the kinetic
parameters of mechanism-based inactivation to inhibitory potency at a particular
time (IC((t))(50)). Using this direct relationship, we observed that the
predicted rank inhibitory potency of a series of MBEIs was improved over that
predicted by the K(I) parameter alone. These relationships offer a fundamental
understanding of the kinetics of MBEI action and may be useful in the evaluation
of these compounds during the discovery process.
PMID- 11015687
TI - Prediction of transdermal flux of prodrugs of 5-fluorouracil, theophylline, and 6
mercaptopurine with a series/parallel model.
AB - Multiple regression analysis of fluxes from suspensions in isopropyl myristate
(J(M)) as a function of molecular weights (MW) and solubilities in isopropyl
myristate (S(IPM)) and water (S(AQ)) were performed on a data set of 41 compounds
(n = 41) comprising 39 prodrugs of 5-fluorouracil (5-FU), theophylline (Th), and
6-mercaptopurine (6-MP), in addition to 5-FU and Th, using four models. Two
series/parallel models have been developed that allow an aqueous-only path in
parallel with a lipid-only path and with a lipid-aqueous series path for the
permeation of solutes through skin: log J(M) = log ?1/[1/(aS(LIPID) 10(PhiMW)) +
1/(bS(AQ)/MW(1/2))] + cS(LIPID)10(PhiMW) + dS(AQ)/MW(1/2)? where a, b, c, and d
are coefficients for flux through the lipid and aqueous portions of the series
path, the lipid-only path, and the aqueous-only path, respectively, and Phi is
the dependence of diffusivity in lipid on MW. In the first series/parallel model,
S(LIPID) was predicted by S(IPM), and in the second, solvatochromic
series/parallel model, S(LIPID) was predicted by S(IPM)(k MW + Omegai) where
Omega(i) is the sum of the solvatochromic terms alpha, beta, pi, and R(2), and k
is the coefficient for the dependence of partitioning on MW. Using the n = 41
solutions, the coefficients for the aqueous-only path were very small or not
different from zero in the two series/parallel models, so only two-path
series/parallel models were compared with the solvatochromic and transformed
Potts-Guy models where a homogeneous barrier to permeation was assumed. For each
model, one compound at a time was omitted from the data set and new parameter
estimates were obtained for these 41-1 solutions and used to predict log J(M) for
the omitted compound. The average errors of prediction of log J(M) (experimental
log J(M) - predicted log J(M)) for the four models were 0.134 for the
series/parallel (r(2) = 0.937), 0.127 for the solvatochromic series/parallel
(r(2) = 0.967), 0.150 for the solvatochromic (r(2) = 0.950), and 0.134 log units
for the transformed Potts-Guy model (r(2) = 0.944). Thus, the solvatochromic
series/parallel model provides fit and predictive ability comparable to or
slightly superior to previous models that assumed homogeneity of the diffusional
barrier to flux in the rate-determining step, provides further theoretical
support against the existence of a high capacity aqueous-only path, and provides
further insight into the physicochemical properties that should be incorporated
into solutes to optimize their flux. Using the solvatochromic series/parallel
model, the parameter estimates for the n = 41 solution were used to calculate the
flux of each compound through the two paths. For compounds with log partition
coefficients (K(IPM:AQ)) of <0.8, permeation was mostly by the lipid-aqueous
series path; for compounds with log K(IPM:AQ) >1.0, permeation was mostly by the
lipid-only path; the lipid-aqueous series path exhibited the higher carrying
capacity. (c) 2000 Wiley-Liss, Inc.
PMID- 11015688
TI - Determination of average crystallite shape by X-ray diffraction and computational
methods.
AB - The objective of this work was to develop a method to estimate the average shape
and habit of organic crystalline material using X-ray powder diffraction (XRPD),
the single-crystal structure, and computational methods. It is proposed that the
relative intensities of the peaks in an XRPD pattern from a sample exhibiting a
"standard" preferred orientation correlates with the shape of the crystallites
present. Models were developed to yield a quantitative "enhancement" factor for
each face. The combined simple-forms morphology (CSM) of the material was then
produced by indexing the observed faces and modifying the simulated Bravais
Friedel-Donnay-Harker (BFDH) morphology. The average shape of crystallites can be
estimated from the CSM by multiplying each face by its enhancement factor.
Acetaminophen crystals in two different habits and ibuprofen crystallized from
toluene were used. The predicted shapes closely resembled the average shapes
observed with microscopy. Results suggested the average shapes of the organic
crystalline materials can be estimated by XRPD and the computational simulation.
The current limitations are the need to "index" the faces, the size of the
crystallites, and the unknown impact of a polydisperse size distribution on the
calculation. The method must be used within the limits described; however, it is
the only method found that may be adapted to large, more representative sample
sizes. The determination of the average morphology is often a "bottle neck" in
elucidating other important behaviors of large quantities of crystalline powders
used in pharmaceutical development and processing.
PMID- 11015689
TI - Complexation of zolpidem with 2-hydroxypropyl-beta-, methyl-beta-, and 2
hydroxypropyl-gamma-cyclodextrin: effect on aqueous solubility, dissolution rate,
and ataxic activity in rat.
AB - The effect of some chemically modified cyclodextrins [namely, 2-hydroxypropyl
beta-, methyl-beta-, and 2-hydroxypropyl-gamma-cyclodextrin (HP-beta-CD, Me-beta
CD, and HP-gamma-CD, respectively)] on the aqueous solubility and dissolution
rate of the hypnotic agent Zolpidem (ZP) was investigated. Solid complexes were
prepared by freeze drying and characterized by infrared spectroscopy, X-ray
powder diffraction, and differential scanning calorimetry. The solubility and
dissolution rate of the drug were significantly improved by complexation with HP
beta-CD or Me-beta-CD. The structure of the inclusion complex ZP-HP-beta-CD in
CH(3)COOD/D(2)O was investigated by (1)H and (13)C NMR spectroscopy, including
NOE measurements. These measurements revealing a weak interaction between the
tolyl moiety of the guest molecule and the HP-beta-CD cavity. The ataxic activity
in rat was also investigated and it was found that ZP-HP-beta-CD and ZP-Me-beta
CD complexes showed almost 2-fold longer ataxic induction times than controls.
PMID- 11015690
TI - Design of folic acid-conjugated nanoparticles for drug targeting.
AB - The new concept developed in this study is the design of poly(ethylene glycol)
(PEG)-coated biodegradable nanoparticles coupled to folic acid to target the
folate-binding protein; this molecule is the soluble form of the folate receptor
that is overexpressed on the surface of many tumoral cells. For this purpose, a
novel copolymer, the poly[aminopoly(ethylene glycol)cyanoacrylate-co-hexadecyl
cyanoacrylate] [poly(H(2)NPEGCA-co-HDCA)] was synthesized and characterized. Then
nanoparticles were prepared by nanoprecipitation of the obtained copolymer, and
their size, zeta potential, and surface hydrophobicity were investigated.
Nanoparticles were then conjugated to the activated folic acid via PEG terminal
amino groups and purified from unreacted products. Finally, the specific
interaction between the conjugate folate-nanoparticles and the folate-binding
protein was evaluated by surface plasmon resonance. This analysis confirmed a
specific binding of the folate-nanoparticles to the folate-binding protein. This
interaction did not occur with nonconjugated nanoparticles used as control. Thus,
folate-linked nanoparticles represent a potential new drug carrier for tumor cell
selective targeting.
PMID- 11015691
TI - Structural characterization of three crystalline modifications of telmisartan by
single crystal and high-resolution X-ray powder diffraction.
AB - Three crystalline modifications (A, B, and C) of 4'-[[2-n-propyl-4-methyl-6-(1
methyl-benzimidazol-2-yl)benzi midazol-1-yl]methyl]biphenyl-2-carboxylic acid
(INN name, telmisartan) have been detected and their crystal structures have been
determined by single-crystal X-ray diffraction (pseudopolymorph C) and the method
of simulated annealing from high-resolution X-ray powder diffraction data
(polymorphs A and B). The compound is of interest because of its use as an
angiotensin II receptor antagonist. Polymorph A crystallizes in space group
P2(I)/c, Z = 4, with unit cell parameters a = 18.7798(3), b = 18.1043(2), and c =
8.00578(7) A, beta = 97.066(1) degrees, and V = 2701.31 A(3). Polymorph B
crystallizes in space group P2(I)/a, Z = 4, with unit cell parameters a =
16.0646(5), b = 13.0909(3), and c = 13.3231(3) A, beta = 99.402(1) degrees, and V
= 2764.2(1) A(3). The solvated form C crystallizes in space group C2/c, Z = 8,
with unit cell parameters a = 30.990(5), b = 13.130(3), and c = 16.381(3) A, beta
= 95.02(2) degrees, and V = 6639(2) A(3). For the structure solutions of
polymorphs A and B, 13 degrees of freedom (3 translational, 3 orientational, 7
torsion angles) were determined in approximately 2 h of computer time,
demonstrating that the crystal packing and the molecular conformation of medium
sized (MW approximately 500) pharmaceutical compounds can now be solved quickly
and routinely from high-resolution X-ray powder diffraction data.
PMID- 11015692
TI - Effect of zinc binding and precipitation on structures of recombinant human
growth hormone and nerve growth factor.
AB - Metal-induced precipitation of protein therapeutics is being used and further
developed as a processing step in protein formulation and may have utility in
protein purification and bulk storage. In such processes, it is imperative that
native protein structure is maintained and the metal complexation is reversible.
In the current study, we investigated the effects of zinc-induced precipitation
on recombinant human growth hormone (rhGH) and recombinant human nerve growth
factor (rhNGF). On the addition of ethylenediaminetetraacetic acid (EDTA), the
precipitates were dissolved, yielding complete recovery of native protein in both
cases. Both proteins have specific metal binding sites and require specific molar
ratios of zinc to protein to initiate precipitation (zinc:rhGH > 2:1; zinc:rhNGF
> 18:1). Furthermore, the secondary structures of both proteins were unperturbed
in soluble zinc complexes and zinc-induced precipitates, as measured by infrared
and circular dichroism spectroscopies. The soluble zinc complex of rhGH had minor
tertiary structural alterations, whereas zinc binding did not alter the tertiary
structure of rhNGF. These studies indicated that metal-induced precipitation
provides a method to maintain proteins in their native state in precipitates,
which may be useful for purification, storage, and formulation.
PMID- 11015694
TI - Physicochemical and crystallographic evidence for polymorphism of the racemic
ethyl (2-chloromethyl-2,3-dihydro-5H-oxazolo [3, 2-a]pyrimidin-5-one)-6
carboxylate.
AB - The various crystalline forms of an original bicyclic compound [ethyl (2
chloromethyl-2,3-dihydro-5H-oxazolo[3, 2-a]pyrimidin-5-one)-6-carboxylate); EOC]
have been obtained and characterized by powder and single-crystal X-ray
diffraction, differential scanning calorimetry (DSC), and infrared (IR) and Raman
spectroscopy. At 4 degrees C in methanol, a monoclinic racemate (form II)
crystallized from the racemic mixture, whereas at 20 degrees C, an orthorhombic
racemate (form I) was isolated in trichloroethylene. By increasing the
temperature, a solid-solid transition from the stable form II to the stable form
I was observed with a Guinier-Simon camera. A I --> II transformation was
observed at ambient temperature by DSC.
PMID- 11015693
TI - Release characteristics of a short-chain fatty acid, n-butyric acid, from its
beta-cyclodextrin ester conjugate in rat biological media.
AB - 6(A)-O-(n-Butanoyl)-beta-cyclodextrin was prepared and its hydrolysis behavior in
aqueous solutions and in rat intestinal fluids was investigated. Furthermore, the
enzymatic hydrolyses of the n-butyric acid-beta-cyclodextrin conjugate using
alpha-amylase and esterase were studied to gain insight into the release behavior
of n-butyric acid from the conjugate. The hydrolysis of the conjugate proceeded
according to a first-order kinetics in aqueous solution, and gave a V-shaped pH
profile, indicating a specific acid-base-catalyzed hydrolysis at acidic and
neutral-alkaline regions, respectively. The half-lives (t(1/2)) of the conjugate
at pH 4.4, 6.8, and 7.4 at 37 degrees C were approximately 580, 43, and 6 days,
respectively, indicating that the conjugate is stable in aqueous solution. No
appreciable release of n-butyric acid from the conjugate was observed in the
stomach and small intestinal contents of rats, or in the small and large
intestinal homogenates of rats. On the other hand, a fast disappearance of the
conjugate and an appearance of n-butyric acid were observed in the cecal and
colonic contents of rats. The t(1/2) values of the disappearance were
approximately 4, 1, and 6 h in 10 and 15% cecal contents and 10% colonic
contents, respectively, and the appearance of n-butyric acid after 6 h was
approximately 10% in the 15% cecal contents. Aspergillus oryzae alpha-amylase
hydrolyzed the conjugate to small saccharide conjugates, such as the triose and
maltose conjugates, but there was no appreciable release of n-butyric acid. The
conjugate was less susceptible to carboxylic esterase (from porcine live), thus
releasing no appreciable amounts of n-butyric acid. On the other hand, a fast
release of n-butyric acid was observed when the esterase was employed after
amylase hydrolysis, suggesting that two types of enzymes, sugar-degrading and
ester-hydrolyzing enzymes, are necessary for the release of n-butyric acid from
the conjugate in large intestinal contents.
PMID- 11015695
TI - Megacystis-microcolon-intestinal hypoperistalsis syndrome: the difficulties with
antenatal diagnosis. Case report and review of the literature.
AB - Megacystis on antenatal scan in female fetuses is rare and has serious diagnostic
implications. We report two cases of megacystis-microcolon-intestinal
hypoperistalsis syndrome (MMIHS) in female infants in whom antenatal scan
abnormalities were identified, but the diagnosis not made until after delivery.
MMIHS is a rare autosomal recessive condition which is usually lethal in the
first year of life. Prenatal diagnosis is hampered by the lack of specific
diagnostic findings on ultrasound and the absence of an identified genetic locus.
The prenatal findings in MMIHS are reviewed and contrasted with those of other
causes of lower abdominal masses on antenatal ultrasound.
PMID- 11015696
TI - First trimester umbilical artery pulsatility index in fetuses presenting enlarged
nuchal translucency.
AB - The aim of this prospective study was to evaluate an umbilical artery pulsatility
index (UAPI) in first trimester fetuses who present enlarged nuchal translucency
(NT) measurements. UAPI was measured in 121 single fetuses with NT > or =95th
centile, from 10+3 to 13+6 weeks (crown-rump length (CRL) > or =38 mm - < or =84
mm). In these fetuses there were 20 trisomy 21, and six other chromosomal
abnormalities (three trisomy 18 and three monosomy X). Eighty-nine cases had
normal karyotype and delivered a baby without evidence of congenital
malformations. Five fetuses with normal karyotype assessed antenatally were
excluded from the comparison, because of evidence of congenital malformation. A
fetus with normal karyotype that was spontaneously miscarried at 14 weeks' after
chorionic villus sampling was also excluded. UAPI of fetuses with enlarged NT was
compared with those of 65 singleton fetuses with normal NT and normal karyotype,
which were used to establish our terms of reference (5th centile, median and 95th
centile). UAPI of 7/20 (35%) Down syndrome and 42/89 (47%) normal karyotype
fetuses presenting enlarged NT were above the median, and respectively 2/20 (10%)
and 14/89 (15.7%) were above 95th centile of normal NT and normal karyotype
fetuses. No significant differences were demonstrated in the UAPI values amongst
normal karyotype fetuses with normal NT or normal karyotype fetuses with an
enlarged NT or trisomy 21 fetuses with an enlarged NT.
PMID- 11015697
TI - How women deal with the results of serum screening for Down syndrome in the
second trimester of pregnancy.
AB - To gain insight into how pregnant women experience serum screening for Down
syndrome, we sent questionnaires to two groups of relevant subjects in the north
of the Netherlands. The questionnaires addressed the following issues: decision
making process, knowledge and opinions. Questionnaire A was sent to women of 36
years of age and older (n=99) (group A) who were all 20 to 36 weeks pregnant at
that time. In the Netherlands prenatal diagnosis is routinely available to these
women. Questionnaire B was sent to women of younger than 36 years (n=69) (group
B) who had received a screen-positive result and had subsequently undergone
amniocentesis. About half of these women were still pregnant at that time. For
these women, serum screening is only available on the basis of opting-in. The two
questionnaires were largely identical. The response rates to questionnaires A and
B were 82% and 91%, respectively. Group A (women of 36 years and older)
considered that second trimester serum screening made a welcome contribution to
the decision-making process about whether to undergo amniocentesis. Moreover, it
reduced the amniocentesis rate considerably. The vast majority said they would
apply for serum screening in a following pregnancy, but favoured the idea of
first trimester screening. In group B (women of younger than 36 years),
reassurance was the most commonly mentioned reason for undergoing serum
screening. Almost all the women experienced some degree of anxiety when they were
informed about the screen-positive result and 13% continued to be anxious, even
after the favourable result of the amniocentesis. The majority of the respondents
would also apply for serum screening in a following pregnancy and were of the
opinion that this screening should be offered to all pregnant women in the
Netherlands.
PMID- 11015698
TI - Trends in live birth prevalence of down syndrome in the Northern Netherlands 1987
96: the impact of screening and prenatal diagnosis.
AB - In the Northern Netherlands, we examined the live birth prevalence of Down
syndrome (DS) and the impact of maternal serum screening (MSS) and prenatal
cytogenetic diagnosis (PCD) during the period 1987-96. In this period the live
birth prevalence, based on the maternal age distribution and the age specific
risk of delivering a child with DS was expected to increase from 1.26 in 1987 to
1.62 in 1996. The introduction of MSS in 1991 made PCD available to women of all
ages. Nevertheless, the utilization of PCD remained very stable. In 1991, 4.7% of
pregnant women underwent a diagnostic test. In 1996 this percentage was 6.4%. As
a result of MSS and PCD, the live birth prevalence of DS was 19% lower than
expected (p<0.01). Despite utilization of PCD based on opting-in and a
discouraging government policy regarding the offer of MSS, the percentage of DS
cases detected by PCD increased from of 17% during the period 1987-90 to 27% in
the period 1991-96 when MSS was available. The percentages have been corrected
for spontaneous pregnancy loss. From a medical and financial point of view, MSS
was the most cost-effective indication for PCD. However, the potential of
reducing the birth prevalence of DS is limited by the low utilization of MSS and
PCD by pregnant women.
PMID- 11015699
TI - Numbers or words? A randomized controlled trial of presenting screen negative
results to pregnant women.
AB - The Objective of this study was to test the hypothesis that presenting risk
information using numbers rather than words is a more effective way of
communicating the residual risk inherent in a screen negative test result. We
used a randomised controlled trial in a large UK teaching hospital. Two hundred
and twenty pregnant women who received negative results on serum screening for
Down syndrome participated. Presentation of screen negative test results were
given either as a numerical probability (e.g. you have a 1:650 chance of having a
baby with Down syndrome) or as a verbal probability (your chance of having a baby
with Down syndrome is low). In both interventions the verbal anchor 'it is
unlikely that your baby has Down syndrome' was used. Our aims were to measure the
understanding of the residual risk in a screen negative result, and anxiety.
Immediately after receipt of the results, 97% of those receiving their results in
the form of a numerical probability and 91% of those receiving their results in
the form of a verbal probability correctly understood that their baby probably
did not have Down syndrome (95% CI for difference: 0% to 12%; p=0.04). All those
who were incorrect believed that their baby definitely did not have Down
syndrome. Subgroup analysis showed that this effect was confined to those with
lower levels of education (i.e. those without a university degree), amongst whom
understanding was poorer. There was no difference between intervention groups in
understanding the results at four months. There were no differences between
intervention groups in the levels of anxiety at one week or four months after
receiving their results. In conclusion, communicating residual risks using
numbers rather than words has a small beneficial effect of increasing awareness
of residual risks without raising anxiety. Further work is needed to estimate the
size of this effect in less well-informed and less highly educated populations.
PMID- 11015700
TI - The Genoa experience of prenatal diagnosis in NF1.
AB - Type 1 neurofibromatosis (NF1) is an autosomal dominant disorder with an
incidence of about 1 in 3500 live births. Symptoms are highly variable from a few
cafe-au-lait spots and axillary freckling to plexiform neurofibromas, optic
gliomas, pseudarthrosis, and malignancy. Since disease causing mutations are
dispersed throughout the gene, prenatal diagnosis is usually performed in
familial cases by linkage analysis and rarely by direct characterization of the
mutation. We have characterized 48 families and have performed four prenatal
diagnoses. In three cases, the linkage analysis was carried out using informative
markers. A direct approach using the protein truncation test (PTT) and sequencing
was performed in one case in which a R1947X mutation was identified. The extreme
variability of the phenotypic expression of the NF1 gene makes reproductive
decisions in NF1 families very difficult, as molecular diagnosis cannot predict
clinical expression of the disease. The psychological management of the couple is
therefore difficult. In two of the three examined families the reproductive
choices were not influenced by the specific manifestations of the disease in that
family.
PMID- 11015701
TI - How useful is the in vitro expansion of fetal CD34+ progenitor cells from
maternal blood samples for diagnostic purposes?
AB - Fetal cells present in the maternal circulation are a potential source of fetal
DNA that can be used for the development of a prenatal diagnostic test. Since
their numbers are very low, amplification of fetal cells has been discussed for a
long time. So far, most studies have focused on culturing fetal erythroid cells.
In this study, we evaluated whether limiting numbers of fetal haemopoietic
progenitor cells present in an excess of maternal cells were able to overgrow the
maternal component. Therefore, we used a model system in which limiting numbers
of male CD34+ umbilical cord blood cells were diluted in 400 000 female CD34+
peripheral blood cells. The number of XY positive cells derived from umbilical
cord blood was determined using two-colour in situ hybridization with X and Y
chromosomal probes. We demonstrated a 1500-fold relative expansion of male
umbilical cord blood cells over the peripheral blood component after three weeks
of liquid culture, which also corresponded to the extent of expansion of CD34+
cells derived from 20-week fetal blood. However, application of the same culture
protocol to maternal blood samples obtained at 7-16 weeks of gestation showed no
preferential growth of fetal haemopoietic progenitor cells. This study,
therefore, suggests that fetal primitive haemopoietic progenitor cells do either
not circulate in maternal blood before 16 weeks of gestation, or require
different combinations/concentrations of cytokines for their in vitro expansion.
PMID- 11015702
TI - Determination of enzyme activities for prenatal diagnosis of respiratory chain
deficiency.
AB - Genetic counselling and prenatal diagnosis are major issues of mitochondrial
respiratory chain deficiency, especially as these conditions are largely
untreatable. In the absence of known mitochondrial or nuclear gene mutations,
measurement of respiratory chain enzyme activities represents the only
possibility to prevent recurrence of the disease in affected families. We carried
out enzymatic prenatal diagnosis in 21 pregnancies from 10 unrelated couples
using uncultured choriocytes and/or amniocytes. Twelve babies were born and are
healthy, seven pregnancies were discontinued early on because of an enzyme
deficiency detected prenatally. In two cases, a fetus which appeared normal after
early and/or late prenatal diagnosis, turned out to be affected. We conclude that
a deficient enzyme activity is indicative of recurrence, but a normal result at
10 weeks of gestation does not give conclusive evidence as to the outcome of the
pregnancy. We therefore suggest the following procedure: (1) a choriocentesis or
an amniocentesis in early pregnancy when the proband expresses the disease in
cultured skin fibroblasts; (2) a second amniocentesis at 28 weeks' gestation
should be offered to avoid false negative results due to a possible late
expression of the disease, in combination with: (3) a careful and repeated
ultrasound survey for detection of growth failure in the third trimester; (4)
prenatal diagnosis should not be performed in case of late onset clinical
symptoms in the proband; and (5) parents should be aware of the possibility of
false negative results. Prenatal diagnosis should not be proposed for a complex I
deficiency as this enzyme activity cannot be accurately measured in fetal cells.
PMID- 11015703
TI - Mid-trimester beta-hCG levels incorporated in a multifactorial model for the
prediction of severe pre-eclampsia.
AB - Pre-eclampsia remains a major cause of perinatal morbidity and mortality
worldwide. Proposed predicting tests for early detection of pregnant women
destined to develop pre-eclampsia remain unsatisfactory. The aim of this study
was to investigate the clinical utility of combining mid-trimester maternal serum
beta-human chorionic gonadotrophin (MShCG) levels with selected clinical
determining factors as a multifactorial predictive test for pre-eclampsia. Thirty
nine cases with mild pre-eclampsia and 56 with severe pre-eclampsia were
recruited as the study groups. Normotensive women (957) were enrolled as
controls. Potential determining risk factors for severe pre-eclampsia were
selected using a multiple logistic regression to build various combined
prediction models. A receiver-operator characteristic curve was employed to
assess the performance of each prediction test for pre-eclampsia. The prediction
efficacy of each test was examined by the area under the curve (AUC). Our data
show that mid-trimester MShCG levels significantly correlated with severity of
pre-eclampsia (Spearman rank correlation coefficient=0.195, p<0.001). Women with
mild pre-eclampsia had a 2.61-times greater chance, while women with severe pre
eclampsia had a 6.13-times greater chance of having MShCG exceeding 2.0 multiples
of the median than did women with a normal pregnancy. A combined prediction model
composed of MShCG levels, body mass index (BMI), parity, and age as a predictive
test for severe pre-eclampsia was superior to MShCG levels alone (AUC 0.765
versus 0.648). The integrated multifactorial model could identify women at risk
early on for developing severe pre-eclampsia, with a sensitivity of 70% and a
specificity of 71%. Thus, we demonstrate a potentially effective and convenient
method by which women at risk for developing severe pre-eclampsia can be
identified early, based on a multifactorial predictive model composed of
midtrimester MShCG levels, BMI, parity, and age.
PMID- 11015704
TI - Prenatal molecular diagnosis of L1-spectrum disorders.
PMID- 11015705
TI - Antepartum findings in fetal protein C deficiency.
AB - A pregnancy with fetal homozygous protein C deficiency was complicated in the
third trimester by fetal ventriculomegaly, intraorbital thrombosis and placental
infarcts, which could be imaged by combined use of ultrasonography and MRI.
PMID- 11015706
TI - Prenatal diagnosis and genetic analysis of double trisomy 48,XXX,+18.
AB - Prenatal diagnosis of simultaneous occurrence of double trisomy involving
chromosomes 18 and X is extremely rare. We report on the prenatal diagnosis,
genetic analysis and clinical manifestations of a fetus with both trisomy 18 and
trisomy X. A 26-year-old, para 1 woman was referred for genetic counselling at 36
weeks' gestation with the sonographic findings of intrauterine growth retardation
(IUGR), polyhydramnios, ventricular septal defect, and an enlarged cisterna
magna. Both cordocentesis and amniocentesis revealed a consistent karyotype of
48,XXX,+18. Quantitative fluorescent polymerase chain reaction using polymorphic
small tandem repeat markers specific for chromosomes 18 and X rapidly determined
that both aneuploidies arose as a result of non-disjunction in maternal meiosis
II. Our case shows that two non-disjunction events can occur not only in the same
parent, but also in the same cell division. Our case also shows that double
trisomy, 48,XXX,+18, can demonstrate an enlarged cisterna magna, IUGR and
polyhydramnios in prenatal ultrasound.
PMID- 11015707
TI - Prenatal diagnosis and genetic analysis of X chromosome polysomy 49, XXXXY.
AB - We report on the prenatal diagnosis, genetic analysis and clinical manifestations
of a 49,XXXXY fetus. A 31-year-old, primigravida woman was referred for genetic
counselling at 17 weeks' gestation with the sonographic findings of intrauterine
growth retardation, generalized oedema, a large septated cystic hygroma colli
measuring 5x4 cm, and abnormal posturing of the lower extremities. Quantitative
fluorescent polymerase chain reaction (QF-PCR) with small tandem repeat (STR)
markers specific for chromosome X and a pentanucleotide marker X22 for the Xq/Yq
pseudoautosomal region PAR2 rapidly detected the X-chromosome polysomy from
amniotic fluid cells. This abnormality appeared to arise from successive non
disjunction during maternal meiosis I and meiosis II. Cytogenetic analysis
revealed a karyotype of 49,XXXXY. Our case shows that a 49,XXXXY fetus in the
second trimester may demonstrate hydrops fetalis and a large septated cystic
hygroma colli by prenatal ultrasound. Our case also shows that QF-PCR assays with
sex chromosome specific STR markers provide rapid prenatal diagnosis of numerical
sex chromosome aneuploidy as well as its genetic cause in fetal cystic hygroma.
PMID- 11015708
TI - A new approach to prenatal treatment of extralobar pulmonary sequestration.
AB - Fetal hydrothorax and hydrops is a frequent complication of extralobar pulmonary
sequestration which is associated with a high perinatal mortality and severe
respiratory insufficiency in the newborn. In a 27-week-old fetus with this
condition, injection of 1 ml of pure alcohol and pleuro-amniotic shunting
achieved resolution of hydrops. The pregnancy progressed to term and a healthy
neonate was delivered who did not require postnatal surgery.
PMID- 11015709
TI - Prenatal molecular diagnosis of glutaric aciduria type I by direct mutation
analysis.
AB - Various biochemical strategies are followed for the prenatal diagnosis of
glutaric aciduria type I (GA I). However, since the description of patients with
normal excretion of glutarate and significant residual activity, the difficulties
of prenatal biochemical diagnosis are obvious. The characterization of the
glutaryl-CoA dehydrogenase (GCDH) gene has allowed us to develop a single strand
conformation polymorphism (SSCP) screening method, followed by direct sequencing,
to identify the disease causing mutations in patients with GA I. Here we report
the first prenatal diagnoses based on DNA analysis in chorionic villi biopsy or
cultured amniotic fluid cells in three families at risk for GA I. Our results
show that this strategy provides a fast and reliable method for prenatal
diagnosis. In addition we report two new mutations (1209-1210ins G and R161W) in
the GCDH gene that occurred at hypermutable loci.
PMID- 11015710
TI - Prenatal diagnosis of glycogen storage disease type 1b using denaturing high
performance liquid chromatography.
AB - Glycogen storage disease type 1b (GSD1b) is an autosomal recessive inborn error
of metabolism caused by deficiency of glucose-6-phosphate translocase (G6PT1).
Current laboratory diagnosis for GSD1b is established by a functional enzyme
assay of glucose-6-phosphatase in both fresh and detergent-treated liver
homogenates. This procedure requires liver biopsy and is impractical for routine
prenatal diagnosis owing to the high morbidity of fetal liver biopsy. Recently,
the gene for GSD1b has been cloned and the prevalent mutations in different
ethnic groups have been determined. In this study, prenatal molecular diagnosis
was performed for a Chinese family in which a previous child was born homozygous
for the G149E mutation. We detected genomic sequence variants by heteroduplex
formation, followed by denaturing high performance liquid chromatography (DHPLC).
With this method, post-PCR analysis was shortened to 7 min. In the case we
analysed, PCR products amplified from the fetal DNA yielded a single peak in the
chromatogram, indicating a homozygous state in the fetus. When wild-type PCR
products were mixed with fetal PCR products, two peaks were observed, indicating
that the fetus was homozygous for the parental (G149E) mutation. Sequencing
results confirmed this diagnosis. As a result, the pregnancy was terminated and
the diagnosis was confirmed on DNA analysis of the aborted fetus. We show here
that DNA mutation analysis can be used in the prenatal diagnosis of GSD1b and
that DHPLC promises to be a robust technique for this and other prenatal
molecular diagnoses.
PMID- 11015711
TI - Prenatal diagnosis of anophthalmos with limb-body wall complex.
PMID- 11015712
TI - Maternal serum total hCG and free beta-hCG in the first trimester from trisomy 21
pregnancies
PMID- 11015713
TI - Maternal serum total hCG and free beta-hCG in the first trimester from trisomy 21
pregnancies.
PMID- 11015714
TI - Current awareness.
AB - In order to keep subscribers up-to-date with the latest developments in their
field, John Wiley & Sons are providing a current awareness service in each issue
of the journal. The bibliography contains newly published material in the field
of prenatal diagnosis. Each bibliography is divided into 17 sections: 1 Books,
Reviews & Symposia; 2 General Interest; 3 Normal Fetal Development; 4
Gametogenesis and Pre-implantation Diagnosis; 5 First Trimester Diagnosis; 6
Second Trimester Diagnosis; 7 Fetal Diagnosis by Ultrasound and Other Imaging; 8
Maternal Screening; 9 Screening for Carriers of Genetic Abnormality; 10
Technological Developments; 11 Confined Placental Mosaicism and Uniparental
Disomy; 12 Molecular Cytogenetics; 13 Fetal Cells in Maternal Circulation; 14
Fetal Therapy; 15 Psychosocial Aspects; 16 Epidemiology and Environmental
Factors; 17 Developmental Pathology. Within each section, articles are listed in
alphabetical order with respect to author. If, in the preceding period, no
publications are located relevant to any one of these headings, that section will
be omitted
PMID- 11015715
TI - Micrognathozoa: a new class with complicated jaws like those of Rotifera and
Gnathostomulida.
AB - A new microscopic aschelminth-like animal, Limnognathia maerski nov. gen. et sp.,
is described from a cold spring at Disko Island, West Greenland, and assigned to
Micrognathozoa nov. class. It has a complex of jaws in its pharynx, and the
ultrastructure of the main jaws is similar to that of the jaws of advanced
scleroperalian gnathostomulids. However, other jaw elements appear also to have
characteristics of the trophi of Rotifera. Jaw-like structures are found in other
protostome taxa as well-for instance, in proboscises of kalyptorhynch
platyhelminths, in dorvilleid polychaetes and aplacophoran mollusks-but studies
of their ultrastructure show that none of these jaws is homologous with jaws
found in Gnathostomulida, Rotifera, and Micrognathozoa. The latter three groups
have recently been joined into the monophylum Gnathifera Ahlrichs, 1995, an
interpretation supported by the presence of jaw elements with cuticular rods with
osmiophilic cores in all three groups. Such tubular structures are found in the
fulcrum of all Rotifera and in several cuticular sclerites of both
Gnathostomulida and Micrognathozoa. The gross morphology of the pharyngeal
apparatus is similar in the three groups. It consists of a ventral pharyngeal
bulb and a dorsal pharyngeal lumen. The absence of pharyngeal ciliation cannot be
used as an autapomorphy in the ground pattern of the Gnathifera because the
Micrognathozoa has the plesiomorphic alternative with a ciliated pharyngeal
epithelium. The body of Limnognathia maerski nov. gen. et sp. consists of a head,
thorax, and abdomen. The dorsal and lateral epidermis have plates formed by an
intracellular matrix, as in Rotifera and Acanthocephala; however, the epidermis
is not syncytial. The ventral epidermis lacks internal plates, but has a
cuticular oral plate without ciliary structures. Two ventral rows of
multiciliated cells form a locomotory organ. These ciliated cells resemble the
ciliophores present in some interstitial annelids. An adhesive ciliated pad is
located ventrally close to a caudal plate. As in many marine interstitial animals
e.g., gnathostomulids, gastrotrichs, and polychaetes-a special form of tactile
bristles or sensoria is found on the body. Two pairs of protonephridia with
unicellular terminal cells are found in the trunk; this unicellular condition may
be the plesiomorphic condition in Bilateria. Only specimens with the female
reproductive system have been found, indicating that all adult animals are
parthenogenetic females. We suggest that 1) jaws of Gnathostomulida, Rotifera,
and the new taxon, Micrognathozoa, are homologous structures; 2) Rotifera
(including Acanthocephala) and the new group might be sister groups, while
Gnathostomulida could be the sister-group to this assemblage; and 3) the
similarities to certain gastrotrichs and interstitial polychaetes are convergent.
PMID- 11015716
TI - Decription of Limnognathia maerski.
PMID- 11015717
TI - Catecholamine sensitivity in the rat femoral artery after microvascular
anastomosis.
AB - Tissue can demonstrate vasospastic instability after microvascular anastomosis.
This study investigates the in vitro effect of increasing concentrations of
phenylephrine on the rat femoral artery after microvascular anastomosis.
Bilateral groin flaps based on the inferior epigastric artery were raised on 55
Wistar male rats. On the test side, a microvascular anastomosis was performed,
but not on the control side. On days 2-12 postoperatively, the rats were
sacrificed and the femoral arteries harvested and suspended in increasing
concentrations of phenylephrine. The vascular tone on the test and control sides
were recorded and compared. Increased sensitivity was found on the test side as
compared with the control side (P = 0.000). This supersensitivity to
phenylephrine was blocked by the addition of phentolamine and it is believed to
be the result of sympathetic denervation, which occurs when the sympathetic
fibers are cut during the harvesting of the flap. The resulting vascular
instability is believed to contribute to flap failure.
PMID- 11015718
TI - Microvascular surgery in a bloodless field.
AB - Although tourniquets play an integral role in extremity surgery, no clear
guidelines exist for the use of tourniquets in microsurgery. We undertook a study
in 12 healthy volunteers to better understand the coagulation properties of blood
distal to an inflated tourniquet. At a 15-min inflation time, blood distal to an
inflated tourniquet clots faster than blood taken from the opposite arm after
addition of exogenous thrombin (12.5 s vs 17.5 s, P < 0.0001). Neither
fibrinopeptide A (FPA) levels nor tissue plasminogen activator (tPA) levels were
different from those of controls. Tissue factor pathway inhibitor (TFPI), an
endogenous local anticoagulant, was slightly but significantly elevated in
tourniquet blood. Although much remains to be understood, we believe that
microvascular surgery in a bloodless field is safe and efficacious. Nine patients
are presented who successfully underwent microvascular surgery in a bloodless
field, using various types of extremity tourniquets.
PMID- 11015719
TI - Method for morphometric analysis of axons in experimental peripheral nerve
reconstruction.
AB - A new method for morphometric analysis of axons in experimental peripheral nerve
reconstruction is presented. Twelve adult female rabbits were used. In nine
animals the saphenous nerve was transected and stitched epineurially. Three
animals functioned as control. After 3, 6, and 12 months, the nerves were
harvested, fixed in Kryofix and embedded in Histowax. Transverse sections of 6
microm were cut, immunohistochemically stained for NF 90, and counterstained by
Sirius Red. Quantification of nerve fibers in cross sections was performed by
using a confocal laser scanning microscope (CLSM), and the images were stored
digitally. Data analyzing was performed by the Optimas program (5.2).
Calculations were done with Microsoft Excel. The total number of axons, the mean
axon diameter and the percentage axon area/fascicle area were evaluated
statistically. This method for morphologic analysis provides automatically
complete registration of axons and so different methods of experimental nerve
reconstruction can be compared in a fast and reliable way.
PMID- 11015720
TI - Reconstruction after resection of tumors around the knee: role of the free
vascularized fibular graft.
AB - We present our experience with reconstruction after resection of tumors around
the knee, using free vascularized fibular grafting. The study included 23
patients. The lower femur was involved in 17 cases, the upper tibia in 6. The
cases included giant cell tumor of the lower femur (2 patients), giant cell tumor
of the upper tibia (1 patient), malignant fibrous histiocytoma of the lower femur
(1 patient), parosteal osteosarcoma (1 patient), and periosteal osteosarcoma (1
patient). The remaining patients suffered from conventional osteogenic sarcomas.
The size of the defect ranged from 12 to 16 cm in length. Skin flap necrosis
after tumor resection was the most common complication encountered. Other
complications included peroneal nerve involvement in one case and rupture of the
arterial anastomosis in another. All transferred fibulas progressed to union
within 7-9 months. Union time of both upper and lower ends of the fibula and time
of appearance of periosteal reaction were identical. In evaluating periosteal
hypertrophy of the fibula, the hypertrophy (de Boer) index (de Boer HD, Wood MB,
J Bone Joint Surg 1989;71B:374-378) proved unreliable. False positive results are
obtained, when callus formation around the lower end of the femur is far more
abundant than at the upper end of the fibula. For this reason, we introduced the
graft index. The latter is the ratio between the diameter of the graft at its
thinnest portion at latest follow-up to its diameter on the day of operation, as
calculated on plain radiographs. Two of the viable fibulas developed stress
fractures after plate removal. Functional and quality-of -life results were
satisfactory. It is concluded that the free vascularized fibular graft remains a
valuable reconstruction option after the resection of tumors around the knee,
provided certain precautions are followed. First, before closure of the wound,
the skin flaps should be assessed for their viability. Necrotic parts should be
excised. Stable fixation is a necessary prerequisite at the time of operation.
Removal of the fixation device should not be guided by union or periosteal
hypertrophy, but by true widening of the medullary canal.
PMID- 11015721
TI - Vascular complications of native arteriovenous fistulas for hemodialysis: role of
microsurgery.
AB - This article describes the treatment of 56 early and late vascular complications
of native arteriovenous fistula (AVF) in patients with end-stage renal disease,
between January 1987 and January 1999. Twenty-six were arteriovenous aneurysms
and 2 pseudoaneurysms; 25 were thromboses. We also observed two cases of
periarteritis associated with systemic lupus erythematosus (SLE) and one complex
iatrogenic lesion caused by an attempt at percutaneous restoration of potency. We
applied microsurgical principles, instruments, and techniques. It was possible to
restore a vascular access at the original site, using the same vessels in 45
cases (80.4%). In 10.7% of cases, we were able to rescue the original AVF by
microsurgical revision. A new vascular access had to be created proximally in the
same limb or in the contralateral forearm in 11 cases of aneurysms (19.6% of the
total, 42% of the aneurysms). After a minimum follow-up of 8 months, a total of
four patients had to be reoperated for further complications (7.2%). Our data
support the idea that microsurgical treatment of vascular complications of native
AVF is highly successful compared with results obtained by conventional surgery
and, in a defined subgroup of patients, permits salvage of the fistula.
PMID- 11015722
TI - Cellular activity of resident macrophages during Wallerian degeneration.
AB - The resident macrophages have been accepted as an important component of the
peripheral nervous system as Schwann cells. To elucidate their role during
Wallerian degeneration without interference from extrinsic hematogenous
macrophages, we designed a culture system to investigate the behavior of resident
macrophages in vitro. A total of 75 adult male Lewis rats were used; 2. 5-cm
length sciatic nerve explants were harvested. There were three groups. In the
culture groups, the nerve explants were incubated in Dulbecco's modified Eagle's
medium (DMEM) only or in DMEM supplemented with 2 microm forskolin and 10
microg/ml pituitary extract (mitogenic medium for Schwann cells). In vivo
predegenerated nerves and normal nerves were used as the positive and negative
controls, respectively. The observation periods extended to 3 weeks. Hematoxylin
and eosin (H&E) stain was employed to estimate overall cell number in nerve
explants. Macrophages were labeled with ED1; S-100 immunostaining was used to
evaluate the presence of Schwann cells during Wallerian degeneration. Trichrome
stain and toluidine blue stain were used to visualize the fate of myelin. In the
culture groups, the number of resident macrophages increased continuously,
although there were significantly fewer resident macrophages than hematogenous
macrophages after 3 days of Wallerian degeneration (P < 0.01). Morphologically,
resident macrophages contained densely small ED1-positive granules within their
cytoplasm, even at later stages of observation, whereas hematogenous macrophages
contained typical large ED1-positive foam vacuoles characteristic of their mature
phagocytic ability. The cellular activity of Schwann cells was well preserved in
the mitogenic medium; however, myelin removal was not significantly enhanced as
compared with the DMEM groups (P > 0.05). The clearance of myelin debris was
shown to be incomplete in culture groups as compared with the complete removal of
myelin debris in the in vivo groups. Resident macrophages were actively involved
in Wallerian degeneration, but their phagocytic and proliferation ability was
limited. Schwann cells played an adjunctive role during the removal of myelin
debris.
PMID- 11015723
TI - Flap transfers for the treatment of perichondrial ring injuries with soft tissue
defects.
AB - Seven cases (six fresh) of perichondrial ring injury with skin defects were
treated using flap transfers. The study included four boys and three girls
ranging in age from 2 to 9 years (average 6). They were followed up for an
average of 8 years and 10 months. The period from injury to flap coverage was 8
12 days, with an average of 10 days in the fresh cases. Fracture was noted in
four cases, with one an epiphyseal fracture. Peroneal flaps were transferred in
four cases, latissimus dorsi myocutaneous flaps in two, and gastrocnemius muscle
flap in one. Six flaps survived perfectly, and one failed due to venous
thrombosis. This latter case was treated with a cross leg flap. Postoperative
radiographic assessments confirmed partial growth plate arrest in the chronic
case, but all the fresh cases had no postoperative growth disturbance. Flap
coverage, for perichondrial ring injuries with wide skin defects, is a useful
method not only for skin coverage, but for the prevention of growth disturbances
as well.
PMID- 11015724
TI - Schizosaccharomyces pombe gmd3(+)/alg11(+) is a functional homologue of
Saccharomyces cerevisiae ALG11 which is involved in N-linked oligosaccharide
synthesis.
AB - The oligosaccharide of glycoproteins in the fission yeast Schizosaccharomyces
pombe is unique in containing galactose. We isolated four mutants that had
reduced amounts of galactose residues on their cell surface glycoproteins by
fluorescence-activated cell sorter. The isolated four recessive mutants, gmd1 to
gmd4, showed a defect in glycosylation of acid phosphatase, a cell surface
glycoprotein. In gmd3 mutant cells, the amounts of both mannose and galactose
residues were decreased on the cell surface galactomannoproteins, suggesting an
underglycosylation of galactomannoproteins. The gmd3(+) gene encodes a protein
that has significant similarity with Saccharomyces cerevisiae Alg11p and is
likely to be involved in N-linked core oligosaccharide synthesis. ALG11
suppressed the gmd3 mutation, indicating that gmd3(+) gene is a functional
homologue of the ALG11 gene. We therefore designated gmd3(+) as alg11(+).
PMID- 11015725
TI - Purification, molecular and kinetic characterization of phosphofructokinase-1
from the yeast Schizosaccharomyces pombe: evidence for an unusual subunit
composition.
AB - Phosphofructokinase-1 (Pfk-1) from Schizosaccharomyces pombe was purified by 54
fold enrichment to homogeneity elaborating the following steps: (a) Disruption of
the cells with glass beads; (b) fractionated precipitation with polyethylene
glycol 6000; (c) affinity chromatography on Cibacron-Blue F3G-A-Sephadex G 100;
(d) ion exchange chromatography on Resource Q. The native enzyme exhibits a mass
of 790+/-30 kDa, as detected by sedimentation equilibrium measurements. The
apparent sedimentation coefficient was found to be s(20,c)=20.2+/-0.3 S. No
significant dependence of the s-value on the protein concentration was observed
in the range 0. 07-0.7 mg/ml. Polyacrylamide gel electrophoresis in presence of
sodium dodecyl sulphate and MALDI-TOF spectra showed that the enzyme is composed
of subunits of identical size of 100+/-5 kDa, forming an octameric structure. The
N-terminus of the enzyme was found to be blocked. Sequences of tryptic and
chymotryptic peptides of the subunit coincide with the proposed amino acid
sequence as deduced from the gene from the EMBL library. The Pfk-1 coding
sequence of S. pombe was transformed into a Pfk-1 double deletion mutants of
Saccharomyces cerevisiae resulting in glucose-positive cells with enzyme activity
in the crude cell extract. The kinetic analysis revealed less cooperativity to
fructose 6-phosphate (n(H)=1.6) and less inhibition by ATP as compared to the
enzyme from baker's yeast. Fructose 2,6-bisphosphate (in micromolar range) and
AMP (in millimolar range) were found to overcome ATP inhibition and to increase
the affinity to fructose 6-phosphate.
PMID- 11015726
TI - Alcohol acetyltransferases and the significance of ester synthesis in yeast.
AB - This paper reviews our current knowledge of yeast alcohol acyltransferases. Much
of this information has been gathered over the past 10 years through the
application of powerful yeast molecular biology techniques. Evidence from gene
disruption and expression analysis of members of the alcohol acyltransferase
(ATF) gene family indicates that different ester synthases are involved in the
synthesis of esters during alcoholic fermentation. The natural physiological
rationale behind these enzyme activities remains unclear. However, it is believed
that these enzymes may be involved in very different functions, including
cellular fatty acid homeostasis and detoxification mechanisms. Insights into the
regulation of yeast ester synthesis by oxygen and unsaturated fatty acids have
contributed to our understanding of the general mechanisms of gene regulation. In
particular, control mechanisms that underpin the oxygen-mediated regulation of
ATF1 gene transcription appear to be closely linked to those involved in the
regulation of fatty acid metabolism. Data pertaining to the regulation of ATF1
gene transcription have been integrated into a working model for future research.
PMID- 11015727
TI - The yeast Ura2 protein that catalyses the first two steps of pyrimidines
biosynthesis accumulates not in the nucleus but in the cytoplasm, as shown by
immunocytochemistry and Ura2-green fluorescent protein mapping.
AB - The Ura2 multidomain protein catalyses the first two steps of pyrimidines
biosynthesis in Saccharomyces cerevisiae. It consists of a 240 kDa polypeptide
which contains carbamyl phosphate synthetase and aspartate transcarbamylase
domains. The Ura2 protein was believed to be nucleoplasmic, since one of the
aspartate transcarbamylase reaction products, monophosphate, was reported to be
precipitated by lead ions inside nuclei. However, this ultracytochemical approach
was recently shown to give artifactual lead polyphosphate precipitates, and the
use of cerium instead of lead failed to reveal this nucleoplasmic localization.
Ura2 localization has therefore been undertaken by means of three alternative
approaches based on the detection of the protein itself: (a) indirect
immunofluorescence of yeast protoplasts; (b) immunogold labelling of ultrathin
sections of embedded yeast cells (both approaches using affinity purified primary
antibodies directed against the 240 kDa Ura2 polypeptide chain, or against a 22
residue peptide specific of the carbamyl phosphate synthetase domain); and (c)
direct fluorescence of cells expressing an Ura2-green fluorescent protein hybrid.
All three approaches localize the bulk of Ura2 to the cytoplasm, whereas the
signals associated with the nucleus, mitochondria or vacuoles are close to or at
the background level.
PMID- 11015728
TI - Destabilized green fluorescent protein for monitoring dynamic changes in yeast
gene expression with flow cytometry.
AB - Green fluorescent protein (GFP) has many advantages as a reporter molecule, but
its stability makes it unsuitable for monitoring dynamic changes in gene
expression, among other applications. Destabilized GFPs have been developed for
bacterial and mammalian systems to counter this problem. Here, we extend such
advances to the yeast model. We fused the PEST-rich 178 carboxyl-terminal
residues of the G(1) cyclin Cln2 to the C terminus of yEGFP3 (a yeast- and FACS
optimized GFP variant), creating yEGFP3-Cln2(PEST). We tested the hybrid protein
after integrating modules harbouring the yEGFP3 or yEGFP3-CLN2(PEST) ORFs into
the Saccharomyces cerevisiae genome. yEGFP3- Cln2(PEST) had a markedly shorter
half-life (t(1/2)) than yEGFP3; inhibition of protein synthesis with
cycloheximide lead to a rapid decline in GFP content and fluorescence (t(1/2)
approximately 30 min) in cells expressing yEGFP3-Cln2(PEST), whereas these
parameters were quite stable in yEGFP3-expressing cells (t(1/2) approximately 7
h). We placed yEGFP3-CLN2(PEST) under the control of the CUP1 promoter, which is
induced only transiently by copper. This transience was readily discernible with
yEGFP3-Cln2(PEST), whereas yEGFP3 reported only on CUP1 switch-on, albeit more
slowly than yEGFP3-Cln2(PEST). Cell cycle-regulated transcriptional
activation/inactivation of the CLN2 promoter was also discernible with yEGFP3-
Cln2(PEST), using cultures that were previously synchronized with nocodazole. In
comparison to CLN2, expression from the ACT1 promoter was stable after release
from nocodazole. We also applied a novel flow-cytometric technique for cell cycle
analysis with asynchronous cultures. The marked periodicities of CLN2 and CLB2
(mitotic cyclin) transcription were readily evident from cellular yEGFP3
Cln2(PEST) levels with this non-perturbing approach. The results represent the
first reported successful destabilization of a yeast-GFP. This new construct
expands the range of GFP applications open to yeast workers.
PMID- 11015729
TI - Simultaneous overexpression of enzymes of the lower part of glycolysis can
enhance the fermentative capacity of Saccharomyces cerevisiae.
AB - Recombinant S. cerevisiae strains, with elevated levels of the enzymes of lower
glycolysis (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase,
phosphoglycerate kinase, enolase, pyruvate kinase, pyruvate decarboxylase and
alcohol dehydrogenase) were physiologically characterized. During growth on
glucose the enzyme levels in the recombinant strains (YHM4 and YHM7) were 1.1-3.4
fold higher than in the host strain (CEN.PK.K45). The recombinant strains were
grown in aerobic or anaerobic batch cultures on glucose or a mixture of glucose
and galactose. The specific ethanol production rates in the recombinant strains
were the same as for the host strain and the physiological behaviour of the
recombinant strains and the host strain was similar. When the cellular demand for
ATP was increased by means of glucose pulses (final concentrations of 3.9 g/l or
2.0 g/l, respectively) to aerobic chemostat cultures maintained at a dilution
rate of 0.08/h, the specific carbon dioxide production rate (qCO(2)) of
CEN.PK.K45 accelerated at 6x10(-3) mmol/g/min(2) during the first 15 min, whereas
during the same time period the qCO(2) of YHM7 accelerated twice as fast at
12x10(-3) mmol/g/min(2), indicating a higher fermentative capacity in the
recombinant strain.
PMID- 11015730
TI - Diversity of the HO gene encoding an endonuclease for mating-type conversion in
the bottom fermenting yeast Saccharomyces pastorianus.
AB - Two types of HO gene were cloned, sequenced and characterized from the bottom
fermenting yeast Saccharomyces pastorianus. The HO gene present on the 1500 kb
chromosome was designated Sc-HO (S. cerevisiae-type HO), because the nucleotide
sequence of its promoter region and the open reading frame (ORF) was almost
identical to that of the S. cerevisiae laboratory strain HO gene (Lab-HO). The
other HO gene, designated Lg-HO (Lager-fermenting-yeast specific HO), showed 64%
and 83% homology with the promoter and ORF of the Lab-HO at the nucleotide
sequence level, respectively, and was located on the 1100 kb chromosome. Analysis
of the 4 kb DNA fragment amplified from S. bayanus type strain indicated that the
nucleotide sequence of S. bayanus-HO is almost identical to that of the Lg-HO.
The SSB1 gene located downstream of the HO gene in S. cerevisiae was also found
in the 3' distal region of the Sc-HO, Lg-HO and S. bayanus HO genes. These
results showed that the genetic arrangement around the HO loci both of S.
pastorianus and S. bayanus is identical to S. cerevisiae. Southern analysis has
revealed that Saccharomyces sensu stricto contain four types of HO genes; S.
paradoxus-type HO, the Sc-HO, the Lg-HO and S. uvarum-type HO genes. This HO gene
diversity provides useful information for the classification of strains belonging
to Saccharomyces sensu stricto. The S. pastorianus Sc-HO, Lg-HO and S. bayanus-HO
Accession Nos in the DDBJ Nucleotide Sequence Database are AB027449, AB027450 and
AB027451, respectively.
PMID- 11015731
TI - Construction of fission yeast vectors with a novel selection strategy that allows
their use in wild-type fission yeasts.
AB - Novel vectors that use the Pichia pastoris INO1 gene as a selectable marker and
exploit the natural inositol auxotrophy of the fission yeast are described. These
plasmids also contained other features desirable in a plasmid cloning vector.
These plasmids were evaluated in other species of Schizosaccharomyces and found
to replicate autonomously in another variety of S. pombe, S. pombe var.
malidevorans. These plasmids can be used for transformation of any wild-type S.
pombe strain without the need for selection by induced auxotrophic mutations, or
by selection by drug resistance markers, and should greatly assist genetic and
molecular manipulations in these yeasts.
PMID- 11015732
TI - Current awareness on yeast.
PMID- 11015739
TI - Herpesviruses as unrecognised components of the pathogenesis of chronic diseases.
PMID- 11015740
TI - Herpes simplex virus as a cause of Bell's palsy. 1972.
PMID- 11015741
TI - Transient virus infection and multiple sclerosis.
AB - Multiple sclerosis (MS) is a chronic, demyelinating disease of the CNS in which
autoimmunity to myelin plays a role in pathogenesis. The epidemiology of MS
indicates that it may be triggered by a virus infection before the age of
adolescence, but attempts to associate a specific virus with MS have produced
equivocal results. Many studies of the aetiology of MS have postulated that a
persistent virus infection is involved, but transient virus infection may provide
a plausible alternative mechanism that could explain many of the inconsistencies
in MS research. The most studied animal model of MS is chronic relapsing
experimental autoimmune encephalomyelitis (CREAE), which is induced in
susceptible animals following injection of myelin components. While CREAE cannot
provide information on the initiating factor for MS, it may mimic disease
processes occurring after an initial trigger that may involve transient virus
infection. The disease process may comprise separate triggering and relapse
phases. The triggering phase may involve sensitisation to myelin antigens as a
result of damage to oligodendrocytes or molecular mimicry. The relapse phase
could be similar to CREAE, or alternatively relapses may be induced by further
transient virus infections which may not involve infection of the CNS, but which
may involve the recrudescence of anti-myelin autoimmunity. Although current
vaccines have a high degree of biosafety, it is suggested that the measles-mumps
rubella vaccine in particular could be modified to obviate any possibility of
triggering anti-myelin autoimmunity.
PMID- 11015742
TI - The novel receptors that mediate the entry of herpes simplex viruses and animal
alphaherpesviruses into cells.
AB - An extended array of cell surface molecules serve as receptors for HSV entry into
cells. In addition to the heparan sulphate glycosaminoglycans, which mediate the
attachment of virion to cells, HSV requires an entry receptor. The repertoire of
entry receptors into human cells includes molecules from three structurally
unrelated molecular families. They are (i) HveA (herpesvirus entry mediator A),
(ii) members of the nectin family, (iii) 3-O-sulphated heparan sulphate. The
molecules have different attributes and play potentially different roles in HSV
infection and spread to human tissues. All the human entry receptors interact
physically with the virion envelope glycoprotein D (gD). (i) HveA is a member of
the TNF-receptor family. It mediates entry of a restricted range of HSV strains.
Its expression is restricted to few lineages (e.g. T-lymphocytes). (ii) The human
nectin1alpha (HIgR), nectin1delta (PRR1-HveC), and the nectin2alpha (PRR2alpha
HveB) and nectin2delta (PRR2delta) belong to the immunoglobulin superfamily. They
are homologues of the poliovirus receptor (CD155), with which they share the
overall structure of the ectodomain. The human nectin1alpha-delta are broadly
expressed in cell lines of different lineages, are expressed in human tissue
targets of HSV infection, serve as receptors for all HSV-1 and HSV-2 strains
tested and mediate entry not only of free virions, but also cell-to-cell spread
of virus. (iii) The 3-O-sulphated heparan sulphate is expressed in some selected
human cell lines (e.g. endothelial and mast cells) and human tissues, and
mediates entry of HSV-1, but not HSV-2. The human nectin2alpha and nectin2delta
serve as receptors for a narrow range of viruses. A characteristic of the human
nectin1alpha-delta is the promiscuous species non-specific receptor activity
towards the animal alphaherpesviruses, pseudorabies virus (PrV) and bovine
herpesvirus 1 (BHV-1). By contrast with the human nectin1delta, its murine
homologue (mNectin1delta) does not bind gD at detectable level, yet it mediates
entry of HSV, as well as of PrV and BHV-1. This provides the first example of a
mediator of HSV entry independent of a detectable interaction with gD.
PMID- 11015743
TI - Viral genome characterisation by the heteroduplex mobility and heteroduplex
tracking assays.
AB - The heteroduplex mobility assay (HMA) is a means of comparing two PCR amplicons
or, in the variation known as the heteroduplex tracking assay (HTA), a means of
estimating the quasispecies diversity of a viral genome. Heteroduplex assays have
many applications including subtyping viral genomes, screening for low frequency
variants in a population, scanning the relative genetic diversity across a genome
and screening for recombinant clones. They can be used to detect dual infections,
superinfections, contaminated blood products and laboratory contaminations. PCR
amplicons of about 65% sequence similarity or greater will form heteroduplexes
under appropriate conditions, and phylogenetic trees can be drawn from
heteroduplex mobility data. While homoduplexes indicate more than 98% similarity
between two DNA sequences, heteroduplexes indicate at least seven mismatches in a
500-bp amplicon, or a three-base pair gap in 1000-bp. Minority variants
comprising 1% to 5% of the genome population can be detected and quantified by
HTA. Thus far, heteroduplex assays have been described for HIV and other
lentiviruses, hepatitis C and G viruses, Norwalk-like viruses, influenza, measles
and poliovirus. They could be applied to a wide range of other viral species.
PMID- 11015745
TI - E. De clerq, 'Novel compounds in preclinical/early clinical development for the
treatment of HIV infections'. Reviews In medical virology 10(4) 2000, 255-277
AB - The original article to which this Erratum refers was published in Reviews in
Medical Virology 10(4) 2000, 255-277.
PMID- 11015744
TI - Molecular aspects of avian influenza (H5N1) viruses isolated from humans.
AB - In 1997, 18 human infections with H5N1 influenza type A were identified in Hong
Kong and six of the patients died. There were concomitant outbreaks of H5N1
infections in poultry. The gene segments of the human H5N1 viruses were derived
from avian influenza A viruses and not from circulating human influenza A
viruses. In 1999 two cases of human infections caused by avian H9N2 virus were
also identified in Hong Kong. These events established that avian influenza
viruses can infect humans without passage through an intermediate host and
without acquiring gene segments from human influenza viruses. The likely origin
of the H5N1 viruses has been deduced from molecular analysis of these and other
viruses isolated from the region. The gene sequences of the H5N1 viruses were
analysed in order to identify the molecular basis for the ability of these avian
viruses to infect humans.
PMID- 11015747
TI - Another reason to get the lead out.
PMID- 11015746
TI - Heart-healthy eating.
PMID- 11015748
TI - Ask the doctor. My neighbor has atherosclerosis in his leg arteries and he has
been getting chelation therapy. He swears it has made a huge difference and
thinks I should try it for my coronary artery disease. Your advice?
PMID- 11015750
TI - Flu shots.
PMID- 11015749
TI - Ask the doctor. Just two years ago, my total cholesterol was 175 mg/dL, and my
LDL cholesterol was 128 mg/dL. This week my doctor told me that my cholesterol
was 240 and my LDL was 170. I haven't gained any weight or changed my diet-
what's going on?
PMID- 11015752
TI - Surgery. Total knee replacement.
PMID- 11015751
TI - Diet. Tea and health.
PMID- 11015753
TI - Nutrition. Whole fruits and vegetables.
PMID- 11015754
TI - By the way, doctor... In the last five years or so, I've occasionally had an
intense pain on my left side. The doctors tell me that I have diverticulitis and
should think about surgery. I hate the idea. Is it necessary?
PMID- 11015755
TI - SSRIs: Prozac and company - part I.
PMID- 11015756
TI - Adult personality and early experience.
PMID- 11015757
TI - Estrogen not effective for Alzheimer's disease.
PMID- 11015758
TI - Testing cocaine babies.
PMID- 11015759
TI - What is the relationship between schizophrenia and substance abuse?
PMID- 11015760
TI - Dining in, dining out: eating well at home and away.
PMID- 11015761
TI - That lingering cough. Part II: specific causes.
PMID- 11015762
TI - Testosterone for women?
PMID- 11015763
TI - On call. My wife wants me to get more exercise. I play golf three or four times a
week during the nice weather, and I think that's enough. Who is right?
PMID- 11015764
TI - Combating antibiotic resistance.
PMID- 11015765
TI - Breast cancer update, part I.
PMID- 11015766
TI - Boning up on calcium.
PMID- 11015767
TI - By the way, doctor. In the lead article about HRT use in your April issue, you
didn't mention Estrace. I've taken it for several years, without any problems.
But am I getting the same benefits as I would with Premarin, and are the risks
similar?
PMID- 11015768
TI - Complementary and alternative therapies and the question of evidence.
PMID- 11015769
TI - Association of involvement in psychological self-regulation with longer survival
in patients with metastatic cancer: an exploratory study.
AB - There have been numerous anecdotal claims that when patients are dedicated users
of a variety of psychological self-regulation strategies, including relaxation,
mental imaging, cognitive restructuring and meditation, such dedication may have
a life-prolonging effect. Our aim was to test this possibility more rigorously,
in patients with metastatic cancer.A prospective, longitudinal, correlative study
was carried out on 22 patients with varying kinds of medically incurable
metastatic cancer. The intervention was one year of weekly group psychological
therapy. Extensive verbal data (patients' written homework and therapists' notes)
were collected over the year. The extent of each patient's involvement with
psychological work was estimated following a qualitative analysis of these data.
Patients were classed as showing high, moderate, or low involvement on the basis
of a quantitative rating of categories defined by the analysis. These three
subgroups did not differ significantly in their expected median survival duration
as estimated from independent quantitative predictions by a large panel of
oncologists who analyzed the patients' medical charts at time of study entry.A
significant relationship was found between degree of involvement in psychological
work and survival duration. Results are presented as Kaplan-Meier survival curves
(Fig. 2;P = 0. 006, Log Rank test) and as a graphic display of the median
survival of each of the three groups (Fig. 3). The main likely confounders
(medical status, age, quality of life, and attendance at therapy) were similar
across subgroups and did not change the relation between psychological work and
survival duration. Limitations in the design are discussed. However, the strong
effects observed support clinical observations that dedicated involvement in
psychological self-regulation may prolong the life of some patients with
metastatic cancer.
PMID- 11015770
TI - Challenges to the biomedical model: are actions of patients almost always as
important as actions of health professionals in long-term outcomes of chronic
diseases?
PMID- 11015771
TI - Mind-body health at 25: an assessment.
AB - This is a personal assessment of the past 25 years of the mind-body health
movement. It argues that, despite many advances, the movement is notably marred
by its unwillingness to confront the economic and environmental determinants of
health.
PMID- 11015772
TI - Lessons about "The schizophrenia of the body": a comment on Anna Cassirer
Appelbaum's "Observations on the disintegration of the self".
PMID- 11015773
TI - Salient observations and concepts but dubious methodology.
PMID- 11015774
TI - Effect of early mobilisation on grip strength, pinch strength and work of hand
muscles in cases of closed diaphyseal fracture radius-ulna treated with dynamic
compression plating.
AB - AIMS: The purpose of the study was to objectively determine the effects of early
mobilisation in terms of grip strength and work of hand muscles in cases of
closed diaphyseal fracture radius - ulna treated with dynamic compression
plating. SUBJECTS AND METHODS: Fifty normal subjects and Twenty-one patients,
(Eleven patients treated with early active and resistive goal directed
mobilisation and Ten control group) were assessed for pinch strength and grip
strength on Pinch Dynamometer and Jamar Dynamometer and work of hand muscles on
Ergograph. Standardised positions of the equipments and patients were maintained
throughout the study. RESULTS: Results showed highly significant reduction in
performance in patients treated with early mobilisation as compared to normal
subjects in their first assessment (Fourth week post operatively). These patients
showed significant improvement in successive assessments (sixth & eighth post
operative week) on exercising in between these assessments. CONCLUSIONS: There
are significant effects on grip strength and work of hand muscles in patients
treated with that early active and resistive goal directed mobilisation.
PMID- 11015776
TI - JAMA 100 years ago: THE RELATIONS OF SCIENTISTS TO NEWSPAPERS
PMID- 11015775
TI - A piece of my mind: dare we go gently.
PMID- 11015777
TI - JAMA 100 years ago: MEDICAL ORATORY
PMID- 11015778
TI - Nosocomial TB control guidelines debated; will OSHA's proposed regulations
prevail? Occupational Safety and Health Administration.
PMID- 11015779
TI - Hypertension experts recommend new focus on the systolic reading.
PMID- 11015780
TI - New guidelines for common cardiac disease.
PMID- 11015782
TI - From the food and drug administration: new inhaled corticosteroid
PMID- 11015783
TI - From the food and drug administration: new hearing implant approved
PMID- 11015781
TI - From the Food and Drug Administration.
PMID- 11015784
TI - Issues in establishing primary stroke centers.
PMID- 11015785
TI - Issues in establishing primary stroke centers.
PMID- 11015786
TI - Issues in establishing primary stroke centers
PMID- 11015787
TI - Safety precautions to limit exposure from plague-infected patients.
PMID- 11015788
TI - Safety precautions to limit exposure from plague-infected patients.
PMID- 11015789
TI - Safety precautions to limit exposure from plague-infected patients
PMID- 11015790
TI - The role of genotypic resistance testing in selecting therapy for HIV.
PMID- 11015791
TI - The role of genotypic resistance testing in selecting therapy for HIV
PMID- 11015792
TI - The continuing epidemic of obesity in the United States.
PMID- 11015793
TI - Racial differences in knowledge regarding hepatitis C virus infection.
PMID- 11015794
TI - Levels of environmental endotoxin and prevalence of atopic disease.
PMID- 11015795
TI - Effectiveness and cost-benefit of influenza vaccination of healthy working
adults: A randomized controlled trial.
AB - CONTEXT: Although the cost-effectiveness and cost-benefit of influenza
vaccination are well established for persons aged 65 years or older, the benefits
for healthy adults younger than 65 years are less clear. OBJECTIVE: To evaluate
the effectiveness and cost-benefit of influenza vaccine in preventing influenza
like illness (ILI) and reducing societal costs of ILI among healthy working
adults. DESIGN: Double-blind, randomized, placebo-controlled trial conducted
during 2 influenza seasons. SETTING AND PARTICIPANTS: Healthy adults aged 18 to
64 years and employed full-time by a US manufacturing company (for 1997-1998
season, n = 1184; for 1998-1999 season, n = 1191). INTERVENTIONS: For each
season, participants were randomly assigned to receive either trivalent
inactivated influenza vaccine (n = 595 in 1997-1998 and n = 587 in 1998-1999) or
sterile saline injection (placebo; n = 589 in 1997-1998 and n = 604 in 1998
1999). Participants in 1997-1998 were rerandomized if they participated in 1998
1999. MAIN OUTCOME MEASURES: Influenza-like illnesses and associated physician
visits and work absenteeism reported in biweekly questionnaires by all
participants, and serologically confirmed influenza illness among 23% of
participants in each year (n = 275 in 1997-1998; n = 278 in 1998-1999); societal
cost of ILI per vaccinated vs unvaccinated person. RESULTS: For 1997-1998 and
1998-1999, respectively, 95% (1130/1184) and 99% (1178/1191) of participants had
complete follow-up, and 23% in each year had serologic testing. In 1997-1998,
when the vaccine virus differed from the predominant circulating viruses, vaccine
efficacy against serologically confirmed influenza illness was 50% (P =.33). In
this season, vaccination did not reduce ILI, physician visits, or lost workdays;
the net societal cost was $65.59 per person compared with no vaccination. In 1998
1999, the vaccine and predominant circulating viruses were well matched. Vaccine
efficacy was 86% (P =.001), and vaccination reduced ILI, physician visits, and
lost workdays by 34%, 42%, and 32%, respectively. However, vaccination resulted
in a net societal cost of $11.17 per person compared with no vaccination.
CONCLUSION: Influenza vaccination of healthy working adults younger than 65 years
can reduce the rates of ILI, lost workdays, and physician visits during years
when the vaccine and circulating viruses are similar, but vaccination may not
provide overall economic benefits in most years. JAMA. 2000;284:1655-1663.
PMID- 11015796
TI - Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to
chromosome 9q21-q22.
AB - CONTEXT: Occasionally, 2 or more major neurodegenerative diseases arise
simultaneously. An understanding of the genetic bases of combined disorders, such
as amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD), will
likely provide insight into mechanisms of these and related neurodegenerative
diseases. OBJECTIVE: To identify loci that contain genes whose defects cause ALS.
DESIGN: A genome-wide linkage analysis of 2 data sets from an ongoing study begun
in the mid-1980s at 4 university research centers. SUBJECTS: An initial subset of
16 families (549 people) potentially informative for genetic analysis, in which 2
or more individuals were diagnosed as having ALS, identified from a Boston data
set of 400 families and 4 families potentially informative (244 people)
subsequently identified from a Chicago data set of more than 300 families to test
a hypothesis based on findings from the Boston families. MAIN OUTCOME MEASURES:
Linkage calculations assuming autosomal dominant inheritance with age-dependent
penetrance (a parametric logarithm-of-odds [lod] score of 1.0 or greater required
for further study of a potential locus); crossover analysis involving the ALS-FTD
locus. RESULTS: In a set of families in which persons develop both ALS and FTD or
either ALS or FTD alone, a genetic locus that is linked to ALS with FTD located
between markers D9S301 and D9S167 was identified on human chromosome 9q21-q22.
Families with ALS alone did not show linkage to this locus. Crossover analysis
indicates this region covers approximately 17 cM. CONCLUSION: These data suggest
that a defective gene located in the chromosome 9q21-q22 region may be linked to
ALS with FTD. JAMA. 2000;284:1664-1669.
PMID- 11015797
TI - Quality of medical care delivered to Medicare beneficiaries: A profile at state
and national levels.
AB - CONTEXT: Despite condition-specific and managed care-specific reports, no
systematic program has been developed for monitoring the quality of medical care
provided to Medicare beneficiaries. OBJECTIVE: To create a monitoring system for
a range of measures of clinical performance that supports quality improvement and
provides repeated, reliable estimates at the national and state levels for fee
for-service (FFS) Medicare beneficiaries. DESIGN, SETTING, AND PARTICIPANTS:
National study of repeated, cross-sectional observational data collected in 1997
1999 on all Medicare FFS beneficiaries or on a representative sample of
beneficiaries with a particular condition. Data were collected using medical
record abstraction for inpatient care, analysis of Medicare claims for some
ambulatory services, and surveys for immunization rates. Separate samples were
drawn for each topic for each state. MAIN OUTCOME MEASURES: Beneficiary patients'
receipt of 24 process-of-care measures related to primary prevention, secondary
prevention, or treatment of 6 medical conditions (acute myocardial infarction,
breast cancer, diabetes mellitus, heart failure, pneumonia, and stroke) for which
there is strong scientific evidence and professional consensus that the process
of care either directly improves outcomes or is a necessary step in a chain of
care that does so. RESULTS: Across all states for all measures, the percentage of
patients receiving appropriate care in the median state ranged from a high of 95%
(avoidance of sublingual nifedipine for patients with acute stroke) to a low of
11% (patients with pneumonia screened for pneumococcal immunization status before
discharge). The median performance on an indicator is 69% (patients discharged
with heart failure diagnosis who received angiotensin-converting enzyme
inhibitors; diabetic patients having an eye examination in the last 2 years).
Some states (particularly less populous states and those in the Northeast)
consistently ranked high in relative performance while others (particularly more
populous states and those in the Southeast) consistently ranked low. CONCLUSIONS:
It is possible to assemble information on a diverse set of clinical performance
measures that represent performance on the range of services in a health
insurance program. These findings indicate substantial opportunities to improve
the care delivered to Medicare beneficiaries and urgently invite a partnership
among practitioners, hospitals, health plans, and purchasers to achieve that
improvement. JAMA. 2000;284:1670-1676.
PMID- 11015798
TI - Effectiveness of influenza vaccination of day care children in reducing influenza
related morbidity among household contacts.
AB - CONTEXT: A growing proportion of young children in the United States participate
in day care, and these children are considered to be at high risk for influenza
infection. Whether vaccinating day care children reduces household transmission
of influenza is not known. OBJECTIVE: To evaluate the effect of vaccinating day
care children on reducing influenza-related morbidity among their household
contacts. DESIGN: Single-blind, randomized controlled trial conducted during the
1996-1997 influenza season. SETTING: Ten day care centers for children of US Navy
personnel in San Diego, Calif. PARTICIPANTS: A total of 149 day care attendees
(aged 24-60 months) and their families were randomized; 127 children and their
328 household contacts received 2 vaccine doses and were included in the
analysis. INTERVENTIONS: Inactivated influenza vaccine was administered to 60
children with 162 household contacts, and hepatitis A vaccine as a control was
administered to 67 age-matched children with 166 household contacts. MAIN OUTCOME
MEASURES: Information regarding febrile respiratory illnesses and related
morbidity for household contacts of influenza-vaccinated vs control children
(subgrouped by influenza-vaccinated and unvaccinated contacts), obtained by
telephone interviews with parents every 2 weeks from November 1996 through April
1997. RESULTS: Influenza-unvaccinated household contacts (n = 120) of influenza
vaccinated day care children had 42% fewer febrile respiratory illnesses (P =.04)
compared with unvaccinated household contacts of control children. Among school
aged household contacts (aged 5-17 years), there was an 80% reduction among
contacts of vaccinated children (n = 28) vs contacts of unvaccinated children (n
= 31) in febrile respiratory illnesses (P =.01), as well as reductions of more
than 70% in school days missed (P =.02), reported earaches (P =.02), physician
visits (P =.007), physician-prescribed antibiotics (P =.02), and adults who
missed work to take care of ill children (P =.04). CONCLUSIONS: These results
indicate that vaccinating day care children against influenza helps reduce
influenza-related morbidity among their household contacts, particularly among
school-aged contacts. Future studies should be conducted in civilian populations
to assess the full effect of vaccinating day care children against influenza.
JAMA. 2000;284:1677-1682.
PMID- 11015799
TI - Transmission of Mycobacterium tuberculosis from medical waste.
AB - CONTEXT: Washington State has a relatively low incidence rate of tuberculosis
(TB) infection. However, from May to September 1997, 3 cases of pulmonary TB were
reported among medical waste treatment workers at 1 facility in Washington. There
is no previous documentation of Mycobacterium tuberculosis transmission as a
result of processing medical waste. OBJECTIVE: To identify the source(s) of these
3 TB infections. DESIGN, SETTING, AND PARTICIPANTS: Interviews of the 3 infected
patient-workers and their contacts, review of patient-worker medical records and
the state TB registry, and collection of all multidrug-resistant TB (MDR-TB)
isolates identified after January 1, 1995, from the facility's catchment area;
DNA fingerprinting of all isolates; polymerase chain reaction and automated DNA
sequencing to determine genetic mutations associated with drug resistance; and
occupational safety and environmental evaluations of the facility. MAIN OUTCOME
MEASURES: Previous exposures of patient-workers to TB; verification of patient
worker tuberculin skin test histories; identification of other cases of TB in the
community and at the facility; drug susceptibility of patient-worker isolates;
and potential for worker exposure to live M tuberculosis cultures. RESULTS: All 3
patient-workers were younger than 55 years, were born in the United States, and
reported no known exposures to TB. We did not identify other TB cases. The 3
patient-workers' isolates had different DNA fingerprints. One of 10 MDR-TB
catchment-area isolates matched an MDR-TB patient-worker isolate by DNA
fingerprint pattern. DNA sequencing demonstrated the same rare mutation in these
isolates. There was no evidence of personal contact between these 2 individuals.
The laboratory that initially processed the matching isolate sent contaminated
waste to the treatment facility. The facility accepted contaminated medical waste
where it was shredded, blown, compacted, and finally deactivated. Equipment
failures, insufficient employee training, and respiratory protective equipment
inadequacies were identified at the facility. CONCLUSION: Processing contaminated
medical waste resulted in transmission of M tuberculosis to at least 1 medical
waste treatment facility worker. JAMA. 2000;284:1683-1688.
PMID- 11015800
TI - Drug dependence, a chronic medical illness: implications for treatment,
insurance, and outcomes evaluation.
AB - The effects of drug dependence on social systems has helped shape the generally
held view that drug dependence is primarily a social problem, not a health
problem. In turn, medical approaches to prevention and treatment are lacking. We
examined evidence that drug (including alcohol) dependence is a chronic medical
illness. A literature review compared the diagnoses, heritability, etiology
(genetic and environmental factors), pathophysiology, and response to treatments
(adherence and relapse) of drug dependence vs type 2 diabetes mellitus,
hypertension, and asthma. Genetic heritability, personal choice, and
environmental factors are comparably involved in the etiology and course of all
of these disorders. Drug dependence produces significant and lasting changes in
brain chemistry and function. Effective medications are available for treating
nicotine, alcohol, and opiate dependence but not stimulant or marijuana
dependence. Medication adherence and relapse rates are similar across these
illnesses. Drug dependence generally has been treated as if it were an acute
illness. Review results suggest that long-term care strategies of medication
management and continued monitoring produce lasting benefits. Drug dependence
should be insured, treated, and evaluated like other chronic illnesses. JAMA.
2000;284:1689-1695.
PMID- 11015801
TI - Current and future public health challenges.
PMID- 11015802
TI - Preventing influenza in healthy adults: the evolving story.
PMID- 11015803
TI - Further adventures of the tubercle bacillus.
PMID- 11015804
TI - MSJAMA: No one an island: the geography of the whole patient.
PMID- 11015805
TI - MSJAMA: No one an island: the geography of the whole patient
PMID- 11015806
TI - MSJAMA: mind matters, money matters: the cost-effectiveness of mind/body
medicine.
PMID- 11015807
TI - MSJAMA: against the grain: living with the human immunodeficiency virus in rural
South Dakota.
PMID- 11015808
TI - MSJAMA: religion, spirituality, and medicine: application to clinical practice.
PMID- 11015809
TI - MSJAMA: the problem with compliance in diabetes.
PMID- 11015810
TI - Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders.
AB - An extensive literature stretching back decades has shown that prolonged stress
or prolonged exposure to glucocorticoids-the adrenal steroids secreted during
stress-can have adverse effects on the rodent hippocampus. More recent findings
suggest a similar phenomenon in the human hippocampus associated with many
neuropsychiatric disorders. This review examines the evidence for hippocampal
atrophy in (1) Cushing syndrome, which is characterized by a pathologic
oversecretion of glucocorticoids; (2) episodes of repeated and severe major
depression, which is often associated with hypersecretion of glucocorticoids; and
(3) posttraumatic stress disorder. Key questions that will be examined include
whether the hippocampal atrophy arises from the neuropsychiatric disorder, or
precedes and predisposes toward it; whether glucocorticoids really are plausible
candidates for contributing to the atrophy; and what cellular mechanisms underlie
the overall decreases in hippocampal volume. Explicit memory deficits have been
demonstrated in Cushing syndrome, depression, and posttraumatic stress disorder;
an extensive literature suggests that hippocampal atrophy of the magnitude found
in these disorders can give rise to such cognitive deficits.
PMID- 11015811
TI - The hippocampus in patients treated with electroconvulsive therapy: a proton
magnetic resonance spectroscopic imaging study.
AB - BACKGROUND: We monitored the effect of electroconvulsive therapy (ECT) on the
nuclear magnetic resonance-detectable metabolites N-acetylaspartate, creatine and
phosphocreatine, and choline-containing compounds in the hippocampus by means of
hydrogen 1 magnetic resonance spectroscopic imaging. We hypothesized that if ECT
induced memory deterioration was associated with neuronal loss in the
hippocampus, the N-acetylaspartate signal would decrease after ECT and any
increased membrane turnover would result in an increase in the signal from
choline-containing compounds. METHODS: Seventeen patients received complete
courses of ECT, during which repeated proton magnetic resonance spectroscopic
imaging studies of the hippocampal region were performed. Individual changes
during the course of ECT were compared with values obtained in 24 healthy control
subjects and 6 patients remitted from major depression without ECT. RESULTS: No
changes in the hippocampal N-acetylaspartate signals were detected after ECT. A
significant mean increase of 16% of the signal from choline-containing compounds
after 5 or more ECT treatments was observed. Despite the mostly unilateral ECT
application (14 of 17 patients), the increase in the choline-containing compound
signal was observed bilaterally. Lactate or elevated lipid signals were not
detected. All patients showed clinical amelioration of depression after ECT.
CONCLUSIONS: Electroconvulsive therapy is not likely to induce hippocampal
atrophy or cell death, which would be reflected by a decrease in the N
acetylaspartate signal. Compared with an age-matched control group, the choline
containing compounds signal in patients with a major depressive episode was
significantly lower than normal, before ECT and normalized during ECT.
PMID- 11015812
TI - Mental disorders and the incidence of migraine headaches in a community sample:
results from the Baltimore Epidemiologic Catchment area follow-up study.
AB - BACKGROUND: The cross-sectional relation between migraine headaches and affective
disorders has been demonstrated in studies of clinical and community populations.
Few studies have investigated the prospective relation between psychiatric
disorders and migraine headaches. METHODS: A prospective follow-up of the
Baltimore, Md, cohort of the Epidemiologic Catchment Area Study assessed
psychopathologic features in 1981 and again between 1993 and 1996. Interviews
included a history of headaches at baseline and self-reported assessment of
migraine headaches at follow-up. Risk estimates for incident migraine headaches
by 1981 demographic variables and psychopathologic features were calculated. The
cross-sectional association between prevalent migraine and lifetime psychiatric
diagnoses was estimated. RESULTS: In the at-risk population of 1343, there were
118 incident cases of migraine headaches. The age- and sex-specific incident
rates of migraine headaches followed the expected patterns, with younger age and
female sex identified as risk factors. In cross-sectional analyses, major
depression (odds ratio, 3.14; 95% confidence interval, 2.03-4. 84) and panic
disorder (odds ratio, 5.09; 95% confidence interval, 2. 65-9.79) had the
strongest associations, and alcohol and other substance abuse were not
associated. In logistic regression models including age, sex, and psychiatric
illness in 1981, only phobia was predictive of incident migraines (odds ratio,
1.70; 95% confidence interval, 1.11-2.58). Affective disorders were not
predictive of incident migraine headaches. Including a history of tricyclic
antidepressant use did not change the results. CONCLUSIONS: There is a strong
cross-sectional relation between affective disorders and migraine headaches in
this cohort. However, there is no association between antecedent affective
disorders and incident migraine headaches in this population-based prospective
study.
PMID- 11015813
TI - Childhood sexual abuse and adult psychiatric and substance use disorders in
women: an epidemiological and cotwin control analysis.
AB - BACKGROUND: Women who report childhood sexual abuse (CSA) are at increased risk
for developing psychiatric disorders in adulthood. What is the diagnostic
specificity and cause of this association? METHODS: In a population-based sample
of 1411 female adult twins, 3 levels of CSA were assessed by self-report and
cotwin report: nongenital, genital, and intercourse. Interviews with twins and
parents assessed family background and diagnoses of psychiatric and substance
dependence disorders. Odds ratios (ORs) were calculated by logistic regression.
RESULTS: By self-report, 30.4% reported any CSA and 8.4% reported intercourse.
Self-reported CSA was positively associated with all disorders, the highest ORs
being seen with bulimia and alcohol and other drug dependence. The ORs were
modest and often nonsignificant with nongenital CSA and increased with genital
CSA and especially intercourse, where most ORs exceeded 3.0. A similar pattern of
findings was seen with CSA as reported by the cotwin, although many ORs were
smaller. Controlling for family background factors and parental psychopathology
produced a small to modest reduction in ORs. In twin pairs discordant for CSA,
the exposed twin was at consistently higher risk of illness. CONCLUSIONS: Women
with CSA have a substantially increased risk for developing a wide range of
psychopathology. Most of this association is due to more severe forms of CSA and
cannot be explained by background familial factors. Although other biases cannot
be ruled out, these results are consistent with the hypothesis that CSA is
causally related to an increased risk for psychiatric and substance abuse
disorders.
PMID- 11015814
TI - Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill
comparison group.
AB - BACKGROUND: To examine the relationship between respiratory regulation and
childhood anxiety disorders, this study considered the relationship between
anxiety disorders and symptoms during carbon dioxide (CO(2)) exposure, CO(2)
sensitivity in specific childhood anxiety disorders, and the relationship between
symptomatic and physiological responses to CO(2). METHODS: Following procedures
established in adults, 104 children (aged 9-17 years), including 25 from a
previous study, underwent 5% CO(2) inhalation. The sample included 57 probands
with an anxiety disorder (social phobia, generalized anxiety disorder, separation
anxiety disorder, and panic disorder) and 47 nonill comparison subjects. Symptoms
of anxiety were assessed before, during, and after CO(2) inhalation. RESULTS: All
children tolerated the procedure well, experiencing transient or no increases in
anxiety symptoms. Children with an anxiety disorder, particularly separation
anxiety disorder, exhibited greater changes in somatic symptoms during inhalation
of CO(2)-enriched air, relative to the comparison group. During CO(2) inhalation,
symptom ratings were positively correlated with respiratory rate increases, as
well as with levels of tidal volume, minute ventilation, end-tidal CO(2), and
irregularity in respiratory rate during room-air breathing. CONCLUSIONS:
Childhood anxiety disorders, particularly separation anxiety disorder, are
associated with CO(2) hypersensitivity, as defined by symptom reports. Carbon
dioxide hypersensitivity is associated with physiological changes similar to
those found in panic disorder. These and other data suggest that certain
childhood anxiety disorders may share pathophysiological features with adult
panic disorder.
PMID- 11015815
TI - Olanzapine treatment of psychotic and behavioral symptoms in patients with
Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo
controlled trial. The HGEU Study Group.
AB - BACKGROUND: Patients with Alzheimer disease (AD) commonly exhibit psychosis and
behavioral disturbances that impair patient functioning, create caregiver
distress, and lead to institutionalization. This study was conducted to assess
the efficacy and safety of olanzapine in treating psychosis and/or
agitation/aggression in patients with AD. METHODS: A multicenter, double-blind,
placebo-controlled, 6-week study was conducted in 206 elderly US nursing home
residents with AD who exhibited psychotic and/or behavioral symptoms. Patients
were randomly assigned to placebo or a fixed dose of 5, 10, or 15 mg/d of
olanzapine. The primary efficacy measure was the sum of the Agitation/Aggression,
Hallucinations, and Delusions items (Core Total) of the Neuropsychiatric
Inventory-Nursing Home version. RESULTS: Low-dose olanzapine (5 and 10 mg/d)
produced significant improvement compared with placebo on the Core Total (-7.6 vs
-3.7 [P<.001] and -6.1 vs -3. 7 [P =.006], respectively). Core Total improvement
with olanzapine, 15 mg/d, was not significantly greater than placebo. The
Occupational Disruptiveness score, reflecting the impact of patients' psychosis
and behavioral disturbances on the caregiver, was significantly reduced in the 5
mg/d olanzapine group compared with placebo (-2.7 vs -1.5; P =.008). Somnolence
was significantly more common among patients receiving olanzapine (25.0%-35.8%),
and gait disturbance occurred in those receiving 5 or 15 mg/d (19.6% and 17.0%,
respectively). No significant cognitive impairment, increase in extrapyramidal
symptoms, or central anticholinergic effects were found at any olanzapine dose
relative to placebo. CONCLUSION: Low-dose olanzapine (5 and 10 mg/d) was
significantly superior to placebo and well tolerated in treating
agitation/aggression and psychosis in this population of patients with AD.
PMID- 11015816
TI - Mental disorders and violence in a total birth cohort: results from the Dunedin
Study.
AB - BACKGROUND: We report on mental disorders and violence for a birth cohort of
young adults, regardless of their contact with the health or justice systems.
METHODS: We studied 961 young adults who constituted 94% of a total-city birth
cohort in New Zealand, April 1, 1972, through March 31, 1973. Past-year
prevalence of mental disorders was measured using standardized DSM-III-R
interviews. Past-year violence was measured using self-reports of criminal
offending and a search of official conviction records. We also tested whether
substance use before the violent offense, adolescent excessive perceptions of
threat, and a juvenile history of conduct disorder accounted for the link between
mental disorders and violence. RESULTS: Individuals meeting diagnostic criteria
for alcohol dependence, marijuana dependence, and schizophrenia-spectrum disorder
were 1.9 (95% confidence interval [CI], 1.0-3.5), 3.8 (95% CI, 2.2-6.8), and 2.5
(95% CI, 1.1-5.7) times, respectively, more likely than control subjects to be
violent. Persons with at least 1 of these 3 disorders constituted one fifth of
the sample, but they accounted for half of the sample's violent crimes (10% of
violence risk was uniquely attributable to schizophrenia-spectrum disorder).
Among alcohol-dependent individuals, violence was best explained by substance use
before the offense; among marijuana-dependent individuals, by a juvenile history
of conduct disorder; and among individuals with schizophrenia-spectrum disorder,
by excessive perceptions of threat and a history of conduct disorder.
CONCLUSIONS: In the age group committing most violent incidents, individuals with
mental disorders account for a considerable amount of violence in the community.
Different mental disorders are linked to violence via different core
explanations, suggesting multiple-targeted prevention strategies.
PMID- 11015818
TI - Contrast detection in schizophrenia.
PMID- 11015817
TI - Cost-effectiveness of clozapine compared with conventional antipsychotic
medication for patients in state hospitals.
AB - BACKGROUND: An open-label, randomized controlled trial compared clozapine with
physicians'-choice medications among long-term state hospital inpatients in
Connecticut. The goal was to examine clozapine's cost-effectiveness in routine
practice for people experiencing lengthy hospitalizations. METHODS: Long-stay
patients with schizophrenia in a state hospital were randomly assigned to begin
open-label clozapine (n = 138) or to continue receiving conventional
antipsychotic medications (n = 89). We interviewed study participants every 4
months for 2 years to assess psychiatric symptoms and functional status, and we
collected continu